Ventricular endocardial tissue geometry influences stimulus threshold and effective refractory period

Understanding the biophysical processes by which electrical stimuli applied to cardiac tissue may result in local activation is important in both the experimental and clinical electrophysiology laboratory environments, as well as gaining a more in-depth knowledge of the mechanisms of focal trigger-induced arrhythmias. Previous computational models have predicted that local myocardial tissue architecture alone may significantly modulate tissue excitability, affecting both the local stimulus current required to excite the tissue and the local effective refractory period (ERP).

https://ift.tt/2RIhQXv

Clinical Validation of the Comprehensive Complication Index as a Measure of Postoperative Morbidity at a Surgical Department: A Prospective Study

Objective: Using clinical outcomes, to validate the comprehensive complication index (CCI) as a measure of postoperative morbidity in all patients undergoing surgery at a general surgery department. Background: The Clavien-Dindo classification (CDC) is the most widely used system to assess postoperative morbidity. The CCI is a numerical scale based on the CDC. Once validated, it could be used universally to establish and compare the real postoperative complications of each surgical procedure. Methods: Observational prospective cohort study. All patients who underwent surgery during the 1-year study period were included. All the complications graded with the CDC and related to the initial admission, or until discharge if the patient was readmitted within 90 days of surgery, were included. Surgical procedures were classified according to the operative severity score (OSS) as minor, moderate, major, or major+. The clinical validation of the CCI was performed by assessing its correlation with 4 different clinical outcomes. Results: A total of 1850 patients were included: 513 (27.7%) presented complications and 101 (5.46%) were readmitted. In the multivariate analysis, the CCI and CDC were associated with postoperative stay, prolongation of postoperative stay, readmission, and disability in all OSS groups (P

https://ift.tt/2yhdTlf

Principal ignorability in mediation analysis: through and beyond sequential ignorability

Summary

In causal mediation analysis, the definitions of the natural direct and indirect effects involve potential outcomes that can never be observed, so-called a priori counterfactuals. This conceptual challenge translates into issues in identification, which requires strong and often unverifiable assumptions, including sequential ignorability. Alternatively, we can deal with post-treatment variables using the principal stratification framework, where causal effects are defined as comparisons of observable potential outcomes. We establish a novel bridge between mediation analysis and principal stratification, which helps to clarify and weaken the commonly used identifying assumptions for natural direct and indirect effects. Using principal stratification, we show how sequential ignorability extrapolates from observable potential outcomes to a priori counterfactuals, and propose alternative weaker principal ignorability-type assumptions. We illustrate the key concepts using a clinical trial.

https://ift.tt/2z16lnk

A convex formulation for high-dimensional sparse sliced inverse regression

Summary

Sliced inverse regression is a popular tool for sufficient dimension reduction, which replaces covariates with a minimal set of their linear combinations without loss of information on the conditional distribution of the response given the covariates. The estimated linear combinations include all covariates, making results difficult to interpret and perhaps unnecessarily variable, particularly when the number of covariates is large. In this paper, we propose a convex formulation for fitting sparse sliced inverse regression in high dimensions. Our proposal estimates the subspace of the linear combinations of the covariates directly and performs variable selection simultaneously. We solve the resulting convex optimization problem via the linearized alternating direction methods of multiplier algorithm, and establish an upper bound on the subspace distance between the estimated and the true subspaces. Through numerical studies, we show that our proposal is able to identify the correct covariates in the high-dimensional setting.

https://ift.tt/2RKUtfR

Statistical sparsity

Summary

The main contribution of this paper is a mathematical definition of statistical sparsity, which is expressed as a limiting property of a sequence of probability distributions. The limit is characterized by an exceedance measure $H$ and a rate parameter $\rho > 0$, both of which are unrelated to sample size. The definition encompasses all sparsity models that have been suggested in the signal-detection literature. Sparsity implies that $\rho$ is small, and a sparse approximation is asymptotic in the rate parameter, typically with error $o(\rho)$ in the sparse limit $\rho \to 0$. To first order in sparsity, the sparse signal plus Gaussian noise convolution depends on the signal distribution only through its rate parameter and exceedance measure. This is one of several asymptotic approximations implied by the definition, each of which is most conveniently expressed in terms of the zeta transformation of the exceedance measure. One implication is that two sparse families having the same exceedance measure are inferentially equivalent and cannot be distinguished to first order. Thus, aspects of the signal distribution that have a negligible effect on observables can be ignored with impunity, leaving only the exceedance measure to be considered. From this point of view, scale models and inverse-power measures seem particularly attractive.

https://ift.tt/2yXHJvp

Integrative linear discriminant analysis with guaranteed error rate improvement

Summary

Multiple types of data measured on a common set of subjects arise in many areas. Numerous empirical studies have found that integrative analysis of such data can result in better statistical performance in terms of prediction and feature selection. However, the advantages of integrative analysis have mostly been demonstrated empirically. In the context of two-class classification, we propose an integrative linear discriminant analysis method and establish a theoretical guarantee that it achieves a smaller classification error than running linear discriminant analysis on each data type individually. We address the issues of outliers and missing values, frequently encountered in integrative analysis, and illustrate our method through simulations and a neuroimaging study of Alzheimer's disease.

https://ift.tt/2RI5QW0

The change-plane Cox model

Summary

We propose a projection pursuit technique in survival analysis for finding lower-dimensional projections that exhibit differentiated survival outcomes. This idea is formally introduced as the change-plane Cox model, a nonregular Cox model with a change-plane in the covariate space that divides the population into two subgroups whose hazards are proportional. The proposed technique offers a potential framework for principled subgroup discovery. Estimation of the change-plane is accomplished via likelihood maximization over a data-driven sieve constructed using sliced inverse regression. Consistency of the sieve procedure for the change-plane parameters is established. In simulations the sieve estimator demonstrates better classification performance for subgroup identification than alternatives.

https://ift.tt/2z26ZRi

Cancers, Vol. 10, Pages 430: Recent Studies on Ponatinib in Cancers Other Than Chronic Myeloid Leukemia

Cancers, Vol. 10, Pages 430: Recent Studies on Ponatinib in Cancers Other Than Chronic Myeloid Leukemia

Cancers doi: 10.3390/cancers10110430

Authors: Francesca Musumeci Chiara Greco Giancarlo Grossi Alessio Molinari Silvia Schenone

Ponatinib is a third line drug for the treatment of chronic myeloid leukemia patients, especially those that develop the gatekeeper mutation T315I, which is resistant to the first and the second line drugs imatinib, nilotinib, dasatinib and bosutinib. The compound was first identified as a pan Bcr-Abl and Src kinase inhibitor. Further studies have indicated that it is a multitargeted inhibitor that is active on FGFRs, RET, AKT, ERK1/2, KIT, MEKK2 and other kinases. For this reason, the compound has been evaluated on several cancers in which these kinases play important roles, including thyroid, breast, ovary and lung cancer, neuroblastoma, rhabdoid tumours and in myeloproliferative disorders. Ponatinib is also being tested in clinical trials to evaluate its activity in FLT3-ITD acute myelogenous leukemia, head and neck cancers, certain type of lung cancer, gastrointestinal stromal tumours and other malignancies. In this review we report the most recent preclinical and clinical studies on ponatinib in cancers other than CML, with the aim of giving a complete overview of this interesting compound.

https://ift.tt/2yZ6urc

Tumor clonality and resistance mechanisms in EGFR mutation-positive non-small-cell lung cancer: implications for therapeutic sequencing

Future Oncology, Ahead of Print.


https://ift.tt/2Oyn3iL

Efficacy and safety of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with type 2 diabetes: a systematic review and network meta-analysis study protocol

Introduction

Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are two classes of glucose-lowering drugs gaining popularity in the treatment of type 2 diabetes mellitus (T2DM). Current guidelines suggest patient-centred approaches when deciding between available hyperglycaemia drugs with no indication to which specific drug should be administered. Despite systematic reviews and meta-analyses being conducted within SGLT-2is and GLP-1RAs, differences across these classes of drugs have not been investigated. Therefore, this systematic review and network meta-analysis (NMA) will aim to compare the efficacy and safety profiles across and within SGLT-2is and GLP-1RAs.

Methods

PubMed, the Cochrane Central Register of Controlled Trials and ISI Web of Science will be searched from inception for published randomised controlled trials conducted in patients with T2DM, with at least two arms consisting of SGLT-2is, GLP-1RAs or control/placebo. Title and abstracts will be screened by two independent reviewers with conflicts resolved by a third. Data will be extracted by the primary researcher, a random sample will be checked by an independent reviewer. Risk of bias will be assessed using the Cochrane Risk of Bias Tool and overall quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Study characteristics, participants baseline characteristics, mean change in cardiometabolic outcomes and number of adverse events will be extracted for each study. Primary outcome will be the mean change in glycated haemoglobin (HbA_1c) (%, mmol/mol). Initial random-effects pairwise meta-analysis will be conducted for each unique treatment comparison where heterogeneity will be assessed. A Bayesian NMA approach will be adopted where random-effects generalised linear models will be fitted in WinBUGS. Sensitivity analysis will be conducted to assess choices of prior distributions and length of burn-in and sample.

Ethics and dissemination

Ethics approval is not required for this study. Results from this study will be published in a peer-review journal.

PROSPERO registration number

CRD42018091306.

https://ift.tt/2JPeyiw

Cohort profile of the Biomarkers of Acute Serious Illness in Children (BASIC) study: a prospective multicentre cohort study in critically ill children

Purpose

Despite significant progress, challenges remain in the management of critically ill children, including early identification of infection and organ failure and robust early risk stratification to predict poor outcome. The Biomarkers of Acute Serious Illness in Children study aims to identify genetic and biological pathways underlying the development of critical illness in infections and organ failure and those leading to poor outcome (death or severe disability) in children requiring emergency intensive care.

Participants

We recruited a prospective cohort of critically ill children undergoing emergency transport to four paediatric intensive care units (PICUs) in Southeast England between April 2014 and December 2016.

Findings to date

During the study period, 1017 patients were recruited by the regional PICU transport team, and blood and urine samples were obtained at/around first contact with the patient by the transport team. Consent for participation in the study was deferred until after PICU admission and 674 parents/carers were consented. Further samples (blood, urine, stool and throat swabs) were collected after consent. Samples were processed and stored for genomic, transcriptomic, proteomic and metabolomic analyses. Demographic, clinical and laboratory data at first contact, during PICU stay and at discharge, were collected, as were detailed data regarding infectious or non-infectious aetiology. In addition, 115 families have completed 12-month validated follow-up questionnaires to assess quality of life and child behaviour.

The first phase of sample analyses (transcriptomic profiling) is currently in progress.

Future plans

Stored samples will be analysed using genomic, proteomic and metabolic profiling. Advanced bioinformatics techniques will be used to identify biomarkers for early diagnosis of infection, identification of organ failure and risk stratification to predict poor outcome (death/severe disability).

Trial registration number

NCT03238040.

https://ift.tt/2AUDVN2

Association of coronary dominance with the severity of coronary artery disease: a cross-sectional study in Shaanxi Province, China

Objective

To investigate whether coronary artery dominance is associated with the severity of coronary artery disease (CAD).

Design

Cross-sectional study.

Setting

Single-centre.

Participants

Between July 2015 and February 2017, 1654 patients who underwent coronary angiography (CAG) were recruited into this cross-sectional study.

Measurement and methods

According to coronary dominance, patients were classified into left dominance (LD), right dominance (RD) and codominance (CD) based on the CAG results. Multiple linear regression analysis was performed to test the association between severity of CAD and coronary dominance.

Results

The total Gensini score was significantly higher in the RD group than in the left-CD group (42.3±33.6 vs 36.3±29.8; p=0.033). After adjusting for potential confounding factors, the results of multivariate linear regression showed that RD was associated with the severity of CAD (β=6.699, 95% CI 1.193 to 12.205, p=0.017).

Conclusions

The results suggest that right coronary dominance was associated with the severity of CAD.

https://ift.tt/2JNHirQ

Conflict of interest disclosure slides at the European Society of Cardiology Congress 2016 in Rome: are they displayed long enough to assess their content? A cross-sectional study

Objectives

To assess the duration of display of conflict of interest (COI) disclosure slides of presentations at the European Society of Cardiology (ESC) Congress 2016, and to identify factors associated with the duration of display of the disclosure slide.

Design

Cross-sectional observational study.

Outcome measures

Display duration of the COI disclosure slide and display duration per disclosure.

Results

Analysis of official video recordings of all oral presentations, viewed on the ESC website. 1673 oral presentations were analysed. In 706 presentations (42.2%), COIs were present on the disclosure slide. The median display duration of the disclosure slide was 2.49 s (minimum value: 0.16 s; IQR 1.47–4.08). In multivariable analysis, time spent on COI disclosures was positively related to the number of COIs (+0.11 s per extra COI), older estimated age of the speaker (+3.92 s for 75–85 years compared with <25 years), verbally commenting on disclosures (up to +8.25 s) and disclosures being of a non-commercial nature (+2.83 s). In addition, speakers from Eastern, Southern and Western Europe, Africa+East Asia and Asia showed their disclosures significantly shorter than the reference group (Northern Europe).

Conclusion

COI disclosure slides are often displayed too briefly to reasonably assess their content. Several factors appear to influence the duration of display of the COI disclosure slides, but none do so to the degree that the display duration becomes sufficiently long.

https://ift.tt/2AU4WjN

Impact and longevity of measles-associated immune suppression: a matched cohort study using data from the THIN general practice database in the UK

Objective

To test the hypothesis that measles infection increases the incidence of non-measles infectious diseases over a prolonged period of time.

Design

A population-based matched cohort study.

Data sources

This study examined children aged 1–15 years in The Health Improvement Network UK general practice medical records database. Participants included 2228 patients diagnosed with measles between 1990 and 2014, which were matched on age, sex, general practitioner practice and calendar year with 19 930 children without measles. All controls had received at least one measles vaccination. Children with a history of immune-compromising conditions or with immune-suppressive treatment were excluded.

Primary outcome measures

Incidence rate ratio (IRR) of infections, anti-infective prescriptions and all-cause hospitalisations following measles in predetermined periods using multivariate analysis to adjust for confounding variables.

Results

In children with measles, the incidence rate for non-measles infectious disease was significantly increased in each time period assessed up to 5 years postmeasles: 43% in the first month (IRR: 1.43; 95% CI 1.22 to 1.68), 22% from month one to the first year (IRR: 1.22; 95% CI 1.14 to 1.31), 10% from year 1 to 2.5 years (IRR: 1.10; 95% CI 1.02 to 1.19) and 15% (IRR: 1.15; 95% CI 1.06 to 1.25) in years 2.5 to 5 years of follow-up. Children with measles were more than three times as likely to receive an anti-infective prescription in the first month and 15%–24% more likely between the first month and 5 years. The rate of hospitalisation in children with measles was increased only in the month following diagnosis but not thereafter (IRR: 2.83; 95% CI 1.72 to 4.67).

Conclusion

Following measles, children had increased rates of diagnosed infections, requiring increased prescribing of antimicrobial therapies. This population-based matched cohort study supports the hypothesis that measles has a prolonged impact on host resistance to non-measles infectious diseases.

https://ift.tt/2JNHibk

Evaluation of a digital platform for osteoarthritis treatment: study protocol for a randomised clinical study

Introduction

Despite favourable results from structured face-to-face treatment of osteoarthritis (OA) in Sweden through the Better management of patients with OsteoArthritis (BOA) initiative, only around 20% of people with knee or hip OA receive the primary treatment recommended by international guidelines (ie, information, exercise, weight management). In 2014, a digital treatment programme named Joint Academy was introduced in Sweden, based on the same concept as the face-to-face BOA programme. In line with BOA, Joint Academy follows national and international guidelines and best practice for OA treatment. Results from observational studies suggest that this digital treatment is a valuable alternative to the traditional treatment approach and can positively impact patients' function and pain. However, conclusions from such studies commonly suggest that more rigorous testing is necessary to ascertain the benefits of digital treatment delivery for people with OA.

Methods and analysis

A randomised clinical trial will be performed, comparing regular face-to-face care according to BOA with the digital version, Joint Academy. A total of 270 participants with clinically diagnosed knee OA will be recruited at primary care centres and randomised to either standard treatment (BOA) for 3 months, or the experimental group (digital intervention programme). Both groups will receive educational sessions and exercises yet with a difference in programme deliverance. The objective of the trial is to evaluate the effectiveness of the online treatment programme, in comparison with BOA. The two treatment groups will be compared with respect to the number of repetitions of the 30 s chair stand test at 3, 6 and 12 months, using a mixed model repeated measures analysis of variance.

Ethics and dissemination

Ethical approval has been attained from the Regional Board of Ethics in Lund, Sweden (Dnr 2017/719). Results will be published in peer-reviewed journals.

Trial registration number

NCT03328741.

https://ift.tt/2AUDDFW

Complaints from patients with functional neurological disorders: a cross-sectional UK survey of why patients complain and the effect on the clinicians who look after them

Objective

To evaluate the nature of complaints from patients with functional neurological disorders and understand the reaction of UK neurology consultants to receiving complaints from this patient group.

Methods

A voluntary online retrospective survey was advertised to UK consultant neurologists. Questions asked about the nature of the complaint, how it was dealt with, how it affected their emotional well-being and attitude to work, and whether it influenced their clinical practice. Responses were anonymised. The frequency of responses and percentage of total responses were analysed. Respondents were also given opportunities to add personal comments.

Results

Responses from 58 clinicians were received. Patient disagreement with the diagnosis was a factor in 90% of complaints received. Only 77% of complaints were resolved within 6 months and 61% of clinicians received no feedback about the outcome. 31% of clinicians reported their most problematic complaint had an adverse effect on their mood. 67% of respondents changed their practice following the complaint with 59% investigating more frequently or due to perceived pressure from patients.

Conclusions

Complaints from patients with functional neurological disorders appear to be primarily due to disagreement with the diagnosis. They are more difficult to resolve than other complaints, and clinicians who deal with them often become the 'second victim' in the process leading to potentially adverse effects on patient care. Strategies to tackle these issues are discussed.

https://ift.tt/2JRRr6X

Gut Feelings Questionnaire in daily practice: a feasibility study using a mixed-methods approach in three European countries

Objectives

The validated Gut Feelings Questionnaire (GFQ) is a 10-item questionnaire based on the definitions of the sense of alarm and the sense of reassurance. The purpose of the GFQ is to determine the presence or absence of gut feelings in the diagnostic reasoning of general practitioners (GPs).

The aim was to test the GFQ on GPs, in real practice settings, to check whether any changes were needed to improve feasibility, and to calculate the prevalence of the GPs' sense of alarm and sense of reassurance in three different countries.

Setting

Primary care, six participating centres in Belgium, France and the Netherlands.

Participants

We performed a think-aloud study with 24 experienced Dutch GPs, GP trainees and medical clerks who filled in the GFQ after diagnosing each of six case vignettes. We then performed a feasibility study in two phases, using a mixed-method approach, with 42 French and Dutch GPs in the first phase and then 10 Belgian, 10 Dutch and 10 French GPs in the second phase. All GPs filled in the GFQ after each of eight consultations with patients presenting new complaints and were subsequently interviewed about the use of the GFQ.

Outcome measures

GPs' experiences on using the GFQ in real practice, more specifically the average time needed for filling in the questionnaire.

The prevalence of GPs' sense of alarm and sense of reassurance.

Results

The modified version of the GFQ, created without altering the sense of the validated items, was easy to use in daily practice. The prevalence of the GPs' sense of alarm occurred during 23%–31% of the included consultations.

Conclusions

After a two-step study and several minor adaptations, the final version of the GFQ proved to be a feasible and practical tool to be used for prospective observational studies in daily practice.

https://ift.tt/2AVPmnE

Characteristics and prognostic values of traditional pathological parameters and advanced molecular subtypes in women in Beijing with operable breast cancer: a retrospective analysis

Objectives

This study investigated the characteristics and prognostic values of traditional pathological parameters and advanced molecular subtypes in women with operable breast cancer in Beijing.

Design

A retrospective study through case information enquiry or telephonic follow-up.

Setting

Beijing Friendship Hospital.

Participants

1042 patients with primary operable breast cancer between 2008 and 2012 were enrolled in the study.

Measures

The characteristics and 5-year relapse rates according to the Nottingham Prognosis Index (NPI) and molecular subtypes were analysed.

Results

In 1042 patients, the percentages of high histological grade, N1+N2, T2+T4 were 7.3%, 24.2%, 46.9%, respectively. In patients with invasive breast cancer, the percentages of auxiliary staging, positive margins, vascular invasion and nerve infiltration were 65.0%, 2.8%, 10.5% and 1.1%, respectively. The missing percentages of auxiliary staging, margins, vascular tumour invasion and nerve infiltration were 14.2%, 31.4%, 46.5% and 97.4%, respectively. The percentages of ER-positive, PR-positive, HER2-positive and Ki-67 high expression were 64.3%, 43.8%, 18.8% and 62.7%, respectively. The percentages of luminal A, luminal B, HER2-overexpression and basal-like breast cancers were 10.5%, 54.2%, 8.2% and 11.2%, respectively. Luminal A, luminal B and basal-like breast cancer subtypes were more common in the >60 years group, the 41–60 years group and the 20–40 years group, respectively. The 5-year relapse rates according to NPI were as follows: 6.2% in the low recurrence risk group, 10.4% in the moderate recurrence risk group and 12.9% in the high recurrence risk group. The 5-year relapse rates according to molecular subtypes were as follows: luminal A 4.0%, luminal B 7.0%, HER2-overexpression14.2%, basal-like 15.6%.

Conclusions

Reasonable analysis of traditional pathological parameters and advanced molecular subtypes in women with operable breast cancer in Beijing may be useful to guide precise treatment and predict prognosis.

https://ift.tt/2JP1EkH

Assessing the impact of care pathways on potentially preventable complications and costs for spinal trauma patients: protocol for a data linkage study using cohort study and administrative data

Introduction

Traumatic spinal cord injuries have significant consequences both for the injured individual and the healthcare system, usually resulting in lifelong disability. Evidence has shown that timely medical and surgical interventions can lead to better patient outcomes with implicit cost savings. Potentially preventable secondary complications are therefore indicators of the effectiveness of acute care following traumatic injury. The extent to which policy and clinical variation within the healthcare service impact on outcomes and acute care costs for patients with traumatic spinal cord injury (TSCI) in Australia is not well described.

Methods and analysis

A comprehensive data set will be formed using record linkage to combine patient health and administrative records from seven minimum data collections (including costs), with an existing data set of patients with acute TSCI (Access to Care Study), for the time period June 2013 to June 2016. This person-level data set will be analysed to estimate the acute care treatment costs of TSCI in New South Wales, extrapolated nationally. Subgroup analyses will describe the associated costs of secondary complications and regression analysis will identify drivers of higher treatment costs. Mapping patient care and health service pathways of these patients will enable measurement of deviations from best practice care standards and cost-effectiveness analyses of the different pathways.

Ethics and dissemination

Ethics approval has been obtained from the New South Wales Population and Health Services Research Ethics Committee. Dissemination strategies include peer-reviewed publications in scientific journals and conference presentations to enable translation of study findings to clinical and policy audiences.

https://ift.tt/2AUDrGI

Exploring the phase for highest impact on radicality: a cross-sectional study of patient involvement in quality improvement in Swedish healthcare

Objectives

Involving patients in quality improvement is often suggested as a critical step for improving healthcare processes. However, this comes with challenges related to resources, tokenism, validity and competence. Therefore, to optimise the use of available resources, there is a need to understand at what stage in the improvement cycle patient involvement is most beneficial. Thus, the purpose of this study was to identify the phase of an improvement cycle in which patient involvement had the highest impact on radicality of improvement.

Design

An exploratory cross-sectional survey was used.

Setting and methods

A questionnaire was completed by 155 Swedish healthcare professionals (response rate 34%) who had trained and had experience in patient involvement in quality improvement. Based on their replies, the impact of patient involvement on radicality in various phases of the improvement cycle was modelled using the partial least squares method.

Results

Patient involvement in quality improvement might help to identify and realise innovative solutions; however, there is variation in the impact of patient involvement on perceived radicality depending on the phase in which patients become involved. The highest impact on radicality was observed in the phases of capture experiences and taking action, while a moderate impact was observed in the evaluate phase. The lowest impact was observed in the identify and prioritise phase.

Conclusions

Involving patients in improvement projects can enhance the quality of care and help to identify radically new ways of delivering care. This study shows that it is possible to suggest at what point in an improvement cycle patient involvement has the highest impact, which will enable more efficient use of the resources available for patient involvement.

https://ift.tt/2JPeWxz

Hospital postdischarge intervention trialled with family caregivers of older people in Western Australia: potential translation into practice

There is lack of a suitable assessment tool that can be used routinely and systematically by hospital staff to address family caregivers' (FCs') support needs. This paper describes a novel approach to identifying and addressing FCs' needs following hospital discharge of the older person receiving care.

Setting and participants

FC recruitment occurred on the patient's discharge from a tertiary hospital in Western Australia; 64 completed the study; 80% were female; mean age 63.2 years.

Intervention

The Further Enabling Care at Home (FECH) programme was delivered over the telephone by a specially trained nurse and included: support to facilitate understanding of the patient's discharge letter; caregiver support needs assessment and prioritisation of urgent needs; and collaborative guidance, from the nurse, regarding accessing supports.

Results

Sixty-four FCs completed the FECH programme. The top three support needs identified by the FCs were: knowing what to expect in the future (52%), knowing who to contact if they were concerned (52%) and practical help in the home (36%). The telephone-based outreach service worked well and was convenient for the nurse and the FCs, and saved on transport, time and money. Most of the FCs appreciated the systematic approach to identify and articulate their needs and were satisfied with the support they received, mainly navigation through the systems, problem solving, self-care strategies, explanation of illness, symptoms and medication and access to after-hours services.

Conclusions

In order to guide services which may consider adopting this systematic approach to supporting FCs and integrating it into their routine practice, this evaluation of the FECH programme has described the processes implemented and highlighted the factors that hindered or facilitated these processes to engage caregivers with appropriate services in a timely manner. Positive feedback indicated that the programme was a useful addition to hospital discharge planning.

Trial registration number

ACTRN12614001174673; Results.

https://ift.tt/2AVPkfx

Sex differences in the prevalence of neural tube defects and preventive effects of folic acid (FA) supplementation among five counties in northern China: results from a population-based birth defect surveillance programme

Objectives

Sex differences in prevalence of neural tube defects (NTDs) have previously been recognised; however, the different susceptibility of men and women have not been examined in relation to the effects of folic acid (FA) supplementation. We hypothesised that FA may have a disproportionate effect that alters the sex-specific prevalence of NTDs.

Setting

Data from two time points, before (2003–2004) and after (2011–2016) the start of the supplementation programme, were obtained from a population-based birth defect surveillance programme among five counties in northern China. All live births (28 or more complete gestational weeks), all stillbirths of at least 20 weeks' gestational age and pregnancy terminations at any gestational age following the prenatal diagnosis of NTDs were included.

Participants

A total of 25 249 and 83 996 births before and after the programme were included respectively.

Primary and secondary outcome measures

The prevalence of NTDs by sex and subtype, Male:female rate ratios and their 95% CI were calculated.

Results

Overall, NTDs were less prevalent among men than among women (rate ratio (RR) 0.92; 95% CI 0.90 to 0.94), so was anencephaly (RR 0.77; 95% CI 0.73 to 0.81) and encephalocele (RR 0.75; 95% CI 0.61 to 0.92), while spina bifida showed a male predominance (RR 1.10; 95% CI 1.05 to 1.15). The overall prevalence of NTDs decreased by 78/10 000 in men and 108.7/10 000 in women from 2003 to 2004 to 2011 to 2016. There was a significant sex difference in the magnitude of reduction, being greater in women than men, particularly for anencephaly.

Conclusions

The prevalence of NTDs decreased in both sexes after the implementation of a massive FA supplementation programme. While female predominance was observed in open NTDs and total NTDs, they also had a greater rate of decrease in NTDs after the supplementation programme.

https://ift.tt/2JOQ1dz

Observational retrospective study of US national utilisation patterns and live birth rates for various ovarian stimulation protocols for in vitro fertilisation

Objective

Alternative ovarian stimulation protocols for in vitro fertilisation (IVF) have grown in popularity. Yet, patient populations best suited for these protocols have not been defined. Our objective was, therefore, to determine national IVF utilisation patterns and live birth rates of various ovarian stimulation protocols.

Design

Retrospective cohort study.

Setting

Academic-affiliated private fertility centre.

Participants

Aggregate data published by Society for Assisted Reproductive Technology for autologous IVF cycles performed in the USA during 2014 and 2015 were analysed. IVF cycles were stratified based on ovarian stimulation protocol: 205 705 conventional stimulations, 4397 minimal stimulations, 2785 natural cycles and 514 in vitro maturation (IVM) cycles. Repeat cycles could not be determined in this analysis.

Outcome measures

Utilisation patterns and age-specific live birth rates for various ovarian stimulation protocols.

Results

With advancing female age, utilisation of conventional stimulation protocols decreased, while minimal stimulation and natural cycle IVF increased. Diminished ovarian reserve diagnoses were in all age groups less prevalent in patients undergoing conventional stimulation than with all other protocols. Live birth rates were highest with conventional stimulation at 42.4%, 33.1%, 22.1%, 11.7% and 3.9% for <35, 35–37, 38–40, 41–42 and >42 female age groups, respectively. The difference in live birth rates between conventional stimulation and other protocols widened with advancing age from 1.6-fold to 3.9-fold among women <35 years of age, reaching 4.4-fold to 6.6-fold among women >42 years of age.

Conclusions

In comparison to conventional stimulation IVF—minimal stimulation, natural cycle IVF and IVM protocols offer lower but still acceptable live birth rates among young women. These alternative protocols are frequently used in older women and those with diminished ovarian reserve, despite their lower live birth rates. The reasons for this apparent incongruity warrant further careful exploration.

https://ift.tt/2ATtlpA

Stillbirth among women in nine states in India: rate and risk factors in study of 886,505 women from the annual health survey

Objectives

To assess the rate of stillbirth and associated risk factors across nine states in India.

Design

Secondary analysis of cross-sectional data from the Indian Annual Health Survey (2010–2013).

Setting

Nine states in India: Madhya Pradesh, Chhattisgarh, Rajasthan, Uttarakhand, Jharkhand, Odisha, Bihar, Assam and Uttar Pradesh.

Participants

886 505 women, aged 15–49 years.

Main outcome measures

Stillbirth rate with 95% CI. Adjusted OR to examine the associations between stillbirth and (1) socioeconomic, behavioural and biodemographic risk factors and (2) complications in pregnancy (anaemia, eclampsia, other hypertensive disorders, antepartum and intrapartum haemorrhage, obstructed labour, breech presentation, abnormal fetal position).

Results

The overall rate of stillbirth was 10 per 1000 total births (95% CI 9.8 to 10.3). Indicators of socioeconomic deprivation were strongly associated with an increase in stillbirth: rural residence (adjusted OR (aOR) 1.27, 95% CI 1.16 to 1.39), female illiteracy (aOR 1.43, 95% CI 1.17 to 1.74), low socioeconomic status (aOR 2.42, 95% CI 1.82 to 3.21), schedule caste background (aOR 1.11, 95% CI 1.04 to 1.19) and woman not in paid employment (aOR 1.15, 95% CI 1.07 to 1.24). Women from minority religious groups were at higher risk than the Hindu majority (Muslim (aOR 1.33, 95% CI 1.25 to 1.43); Christian (aOR 1.42, 95% CI 1.19 to 1.70)). While a few women smoked (<1%), around 9% reported chewing tobacco, which was associated with an increased odds of stillbirth (aOR 1.11, 95% CI 1.02 to 1.21). Adverse pregnancy and birth characteristics were also associated with stillbirth: antenatal care visits <4 (aOR 1.08, 95% CI 1.01 to 1.15), maternal age <25 years (aOR 1.29, 95% CI 1.21 to 1.37) and ≥35 years (aOR 1.16, 95% CI 1.04 to 1.29), multigravida (aOR 3.06, 95% CI 2.42 to 3.86), multiple pregnancy (aOR 1.77, 95% CI 1.47 to 2.15), assisted delivery (aOR 3.45, 95% CI 3.02 to 3.93), caesarean section (aOR 1.73, 95% CI 1.58 to 1.89), as were pregnancy complications (aOR 1.42, 95% CI 1.33 to 1.51).

Conclusion

India is an emerging market economy experiencing a rapid health transition, yet these findings demonstrate the marked disparity in risk of stillbirth by women's socioeconomic status. Tobacco chewing and maternal and fetal complications were each found to be important modifiable risk factors. Targeting the 'at-risk' population identified here, improved recording of stillbirths and the introduction of local reviews would be important steps to reduce the high burden of stillbirths in India.

https://ift.tt/2JOrjty

Evidence into practice: protocol for a new mixed-methods approach to explore the relationship between trials evidence and clinical practice through systematic identification and analysis of articles citing randomised controlled trials

Introduction

Randomised controlled trials (RCTs) provide high-quality evidence to inform practice. However, much routine care is not based on available RCT evidence. Understanding this disconnect may improve trial design, reporting and implementation. Published literature commenting on RCTs may yield relevant insights. This protocol presents a new approach examining how researchers understand, contextualise and use evidence from RCTs, through analysis of letters, editorials and discussion pieces citing individual RCTs. Surgical case studies will illustrate its ability to identify wide-ranging factors influencing application of trials evidence.

Methods and analysis

In-depth study of published literature will explore written responses to RCTs. After purposefully selecting individual RCTs, we will systematically identify all citing articles covered in Web of Science and Scopus. Editorials, discussions and letters will be included. These are considered most likely to provide critiques and opinions about index RCTs. Original articles and reviews will be excluded. Clinical specialty, RCT design, outcomes and bibliographical data will be collected for RCTs and citing articles. Citing articles will be thematically analysed using the constant comparison technique to explore author understanding, contextualisation and relationship to clinical practice for the index trial. Coding will include generic issues relevant to all RCTs, such as sample size or blinding, and features specific to surgery, such as learning curve. Index trial quality will be examined using validated tools. Results will be combined to create a broad overview of the understanding and use of RCT evidence.

Ethics and dissemination

This study involves secondary use of existing articles and does not require ethical approval. Pilot work will establish its feasibility and inform progression to larger scale utilisation across a broad range of RCTs. Findings will be published in a peer-reviewed journal and presented at surgical and methodological conferences. Results will guide future work on trial design to optimise implementation of results.

https://ift.tt/2ATtCsC

Effectiveness of a free maternal healthcare programme under the National Health Insurance Scheme on skilled care: evidence from a cross-sectional study in two districts in Ghana

Objectives

In her quest to reduce maternal mortality, Ghana introduced a free maternal healthcare programme under the National Health Insurance Scheme. This study aimed to evaluate if women registered with the insurance had a better chance of accessing maternal healthcare services in two districts in Ghana.

Setting

We conducted a cross-sectional quantitative study involving household interviews of all women of the reproductive age group (15–49 years) residing in Kintampo North Municipality and Kintampo South District in Ghana from May to July 2015. Logistics regression analysis at 95% CI was used to determine the independent associations between maternal health insurance and use of antenatal care, facility-based delivery and postnatal care services.

Participants

Women who had children aged 3–12 months were selected to take part in the study.

Results

We observed that women with insurance are 39.5 times more likely to have a maximum of six antenatal care visits and 2.6 times more likely to have an average of four antenatal care visits than those without insurance. Additionally, they are 5.3 times more likely to have facility-based delivery than those without insurance. An association was also found between postnatal care use and insurance as women who do not have insurance are 12.0 (1/0.083) times more likely to receive postnatal care than those with insurance.

Conclusions

Pregnant women who registered with health insurance had at least four antenatal care visits and delivered in a health facility. However majority of them did not go for postnatal care.

https://ift.tt/2JObBPb

Educational disparities in perinatal health in Denmark in the first decade of the 21st century: a register-based cohort study

Objective

To investigate socioeconomic differences in six perinatal health outcomes in Denmark in the first decade of the 21st century.

Design

A population-based cohort study.

Setting

Danish national registries.

Participants

A total of 646 829 live born children and 3076 stillborn children (≥22+0 weeks of gestation) born in Denmark from 2000 to 2009. We excluded children with implausible relations between birth weight and gestational age (n=644), children without information on maternal country of origin (n=138) and implausible values of maternal year of birth (n=36).

Main outcome measures

We investigated the following perinatal health outcomes: stillbirth, neonatal and postneonatal mortality, small-for-gestational age, preterm birth grated into moderate preterm, very preterm and extremely preterm, and congenital anomalies registered in the first year of life.

Results

Maternal educational level was inversely associated with all adverse perinatal outcomes. For all examined outcomes, the risk association displayed a clear gradient across the educational levels. The associations remained after adjustment for maternal age, maternal country of origin and maternal year of birth. Compared with mothers with vocational education, mothers with more than 15 years of education had an adjusted risk ratio for stillbirth of 0.64(95% CI 0.56 to 0.72). The corresponding adjusted risk ratios for neonatal mortality, postneonatal mortality, congenital anomalies, moderate preterm birth and small-for-gestational age were, respectively, 0.79(95% CI 0.67 to 0.93), 0.57(95% CI 0.42 to 0.78), 0.87(95% CI 0.83 to 0.91), 0.80(95% CI 0.77 to 0.83) and 0.83(95% CI 0.81 to 0.85).

Conclusion

Substantial educational inequalities in perinatal health were still present in Denmark in the first decade of the 21st century.

https://ift.tt/2ATsR2K

HIV self-test performance among female sex workers in Kampala, Uganda: a cross-sectional study

Objective

To evaluate HIV self-testing performance and results interpretation among female sex workers (FSWs) in Kampala, Uganda, who performed unassisted HIV self-testing.

Methods

In October 2016, 104 participants used an oral HIV self-test while under observation by research assistants. Participants were not assisted on HIV self-test use prior to or during testing, and were only given the manufacturer's pictorial and written instructions to guide them. Research assistants recorded if participants completed and/or had difficulties with steps in the HIV self-testing process on a prespecified checklist. Randomly drawn, used HIV self-tests were interpreted by FSWs. We calculated the concordance between FSWs' interpretations of self-test results with those indicated in the manufacturer's instructions.

Results

Only 33% (34/104) of participants completed all of the key steps in the HIV self-testing process, and the majority (86%, 89/104) were observed having difficulties with at least one of these steps. Misinterpretation of HIV self-test results were common among FSWs: 23% (12/56) of FSWs interpreted HIV-negative self-test results as HIV positive and 8% (3/37) of FSWs interpreted HIV-positive self-test results as HIV negative. The concordance between FSWs' interpretations of self-test results and that indicated in the instructions was 73% (95% CI 56% to 86%) for HIV-positive self-tests and 68% (95% CI 54% to 80%) for HIV-negative self-tests.

Conclusions

FSWs in Kampala, who performed unassisted HIV self-testing, skipped steps in the HIV self-testing process and had difficulties correctly interpreting self-test results. Training on use and interpretation of HIV self-tests may be necessary to prevent errors in the HIV self-testing process and to avoid the negative consequences of false-positive and false-negative HIV self-test results among FSWs.

Trial registration number

NCT02846402.

https://ift.tt/2JNHcjY

'People like you?: how people with hypertension make sense of future cardiovascular risk--a qualitative study

Objectives

Cardiovascular disease (CVD) prevention guidelines recommend that patients' future CVD risk (as a percentage) is estimated and used to inform shared treatment decisions. We sought to understand the perspectives of patients with hypertension on their future risk of CVD.

Design

Qualitative, semistructured interviews and thematic analysis.

Participants

People with hypertension who had not experienced a cardiovascular event recruited from primary care.

Setting

Participants were purposively sampled from two primary care practices in South London. Interviews were transcribed, and a thematic analysis was conducted.

Results

24 people participated; participants were diverse in age, sex, ethnicity and socioeconomic status. Younger working-aged people were under-represented. Contrasting with probabilistic risk, many participants understood future CVD as binary and unknowable. Roughly half of participants avoided contemplating future CVD risk; for some, lifestyle change and medication obviated the need to think about CVD risk. Some participants identified with one portion of the probability fraction ('I'd be one of those ones.'). Comparison with peers (typically partners, siblings and friends of a similar age, including both 'healthy' and 'unhealthy' people) was most frequently used to describe risk, both among those who engaged with and avoided risk discussion. This contrasts with current risk scores, which describe probabilities in people with similar risk factors; many participants did not identify with such a group, and hence did not find these probabilities meaningful, even where correctly understood.

Conclusions

Risk as typically calculated and communicated (eg, the risk of '100 people like you') may not be meaningful for patients who do not identify with the denominator. Comparing an individual's risk with their peers could be more meaningful.

https://ift.tt/2ATskxM

miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer

miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer

miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer, Published online: 08 November 2018; doi:10.1038/s41419-018-1093-9

miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer

https://ift.tt/2JQ8SF2

Restless Legs Syndrome and Other Movement Disorders of Sleep—Treatment Update

Abstract

Purpose of review

The purpose of this review article is to summarize and discuss the recent advances in the treatment of restless legs syndrome (RLS), as well as REM sleep behavior disorder (RBD), and periodic leg movement disorder (PLMD).

Recent findings

Traditionally, dopaminergic therapy has been considered the sole option for first-line treatment of RLS due to their impressive acute efficacy. Dopamine agonists such as oral pramipexole and ropinirole, as well as transdermal rotigotine are all effective treatment options. However, augmentation of the RLS symptoms is a major limitation of oral dopaminergic therapy. Recently, gabapentinoid agents such as gabapentin enacarbil and pregabalin have shown comparable short-term efficacy to dopaminergics with lower risk of augmentation of the RLS symptoms. Recent evidence on the efficacy of oxycodone-naloxone in treatment-resistant RLS provides an additional therapeutic avenue. The increasing understanding of the role of iron in RLS pathophysiology has led to new options in iron supplementation therapy in RLS, including treatment with ferric carboxymaltose.

Summary

With emerging evidence of augmentation being a side effect specific to dopaminergic treatment, gabapentinoids are considered a safer option as initial treatment. In severe refractory RLS, oxycodone-naloxone can be used. If iron stores are low, IV iron formulations should be the initial treatment choice. New treatment options are needed to address issues with current therapies.

https://ift.tt/2DcSXiV

Novel Surgical Strategies in the Treatment of Gynecological Malignancies

Opinion statement

The main advancement in the surgical treatment of early cervical cancer has been a de-escalation in the radical surgical approach of early stage disease. Similarly, sentinel lymph node detection with cervical tracer injection can be performed alone in microscopic tumors (stage IA) while additional lymphadenectomy is still performed in macroscopic tumors (IB1 and IIA). Parametrial resection has been progressively reduced in tumors less than 2 cm, and simple procedures, conservative (trachelectomy) or not (simple hysterectomy), are currently being evaluated in several phase III trials. Since the preliminary results of the LACC (locally advanced cervical cancer) trial, the value of minimally invasive surgery as the standard approach for the treatment of early stage cervical cancer has been questioned and patients should be aware when discussing the approach for radical hysterectomy. While awaiting the results of ongoing clinical trials comparing radiological and surgical staging in locally advanced cervical cancer patients, surgical staging with paraaortic lymphadenectomy remains the standard of care before definitive chemoradiotherapy in patients with negative aortic PET/TDM. Patients undergoing salvage surgeries for isolated pelvic recurrences of cervical cancer benefit from advanced reconstructive techniques as DIEP flaps and continent reconstructive urinary techniques. In selected patients, a minimally invasive approach can be considered. Surgery is the mainstay of the treatment of endometrial cancer. The major evolution in surgical strategy has occurred in lymph node staging. The standard surgical staging includes pelvic and paraaortic lymph node dissection to the level of the left renal vein. Sentinel lymph node dissection has been validated as a less morbid alternative of systematic lymphadenectomy, indicated in patients with low and intermediate risk of lymph node involvement. In advanced ovarian cancer, complete cytoreduction is the main objective of surgery. To achieve this goal, upper abdominal complex procedures have been developed. Best survival rates are obtained with primary debulking surgery. Exploratory laparoscopy may be performed before cytoreduction to evaluate resectability and thus avoid unnecessary laparotomy. Although systematic pelvic and paraaortic lymphadenectomy is being questioned in patients with advanced ovarian cancer and clinically negative lymph nodes undergoing complete primary debulking surgery, this procedure is still recommended. While waiting publication of the GOG 252 trial, IP chemotherapy after complete CRS is under debate. HIPEC after interval debulking surgery in patients undergoing complete cytoreduction is an intriguing new option. Patients within the first recurrence of ovarian cancer, with score AGO-positive, benefit from a second complete cytoreductive surgery followed by chemotherapy. Ovarian cancer survival rates are higher in specialized high-volume centers, and thus cases should be centralized and quality indicators used.

https://ift.tt/2SUrvvA

Radiation-Related Alterations of Taste Function in Patients With Head and Neck Cancer: a Systematic Review

Opinion statement

Taste sensation is vital for a healthy body as it influences our food intake, acts as a defense mechanism and elicits pleasure. Majority of the head and neck cancer (HNC) patients undergoing radiotherapy suffer from altered taste function and often complain of inability to taste their food, reduced food intake, and weakness. However, there are not many studies conducted to assess this commonly reported side effect. Furthermore, clinical research on radiotherapy-induced taste alterations has proven to be difficult, considering a lack of reliable and validated study tools for assessing objective and subjective outcomes. Developing standardized tools for assessment of taste function and conducting prospective studies in larger population of HNC is the need of the hour. Taste sensation being critically important for sustenance, we need to focus on ways to preserve it. The physical properties of proton particle enable localization of the radiation dose precisely to the tumor and minimizing the exposure of the adjacent healthy tissues. By using Intensity-Modulated Proton Therapy in HNC patients, we anticipate preserving the taste sensation by reducing the dose of radiation to the taste buds.

https://ift.tt/2zHJInw

Cancers, Vol. 10, Pages 429: Novel Agents for Acute Myeloid Leukemia

Cancers, Vol. 10, Pages 429: Novel Agents for Acute Myeloid Leukemia

Cancers doi: 10.3390/cancers10110429

Authors: Mario Luppi Francesco Fabbiano Giuseppe Visani Giovanni Martinelli Adriano Venditti

Acute myeloid leukemia (AML) is a complex hematological disease characterized by genetic and clinical heterogeneity. Recent advances in the understanding of AML pathogenesis have paved the way for the development of new agents targeting specific molecules or mechanisms that contribute to finally move beyond the current standard of care, which is &ldquo;3 + 7&rdquo; regimen. In particular, new therapeutic options such as targeted therapies (midostaurin and enasidenib), monoclonal antibodies (gemtuzumab ozogamicin), and a novel liposomal formulation of cytarabine and daunorubicin (CPX-351) have been recently approved, and will be soon available for the treatment of adult patients with AML. In this review, we will present and describe these recently approved drugs as well as selected novel agents against AML that are currently under investigation, and show the most promising results as monotherapy or in combination with chemotherapy. The selection of these emerging treatments is based on the authors&rsquo; opinion.

https://ift.tt/2PfdSJ8

The Overexpression of CD80 and ISG15 Are Associated with the Progression and Metastasis of Breast Cancer by a Meta-Analysis Integrating Three Microarray Datasets

Abstract

Breast cancer is a common cancer and could result in a substantial mortality. The study aimed to screen gene signatures associated with the development and metastasis of breast cancer and explore their regulation mechanisms. Three datasets of GSE10797, GSE8977 and GSE3744 were downloaded from GEO (Gene Expression Omnibus) database, containing 55 breast cancer samples and 27 normal samples. After data preprocessing using limma software and RMA (robust multi-array average) algorithm, DEGs (differentially expressed genes) between breast tumor and normal tissues in three individual experiments were identified using MADAM package. Function and pathway enrichment analyses were performed for the DEGs. Transcription factors and TAGs (tumor associated genes) among the DEGs were recognized and the PPI (protein-protein-interaction) network for the DEGs was constructed using Cytoscape software. The mRNA expression was analyzed via real-time quantitative PCR and protein expression was measured by western blotting. Totally, 100 DEGs were identified, including 33 up-regulated genes and 67 down-regulated genes. Among them, up-regulated DEGs such as CD80 was enriched in toll-like receptor (TLR) interaction pathway and the TAG, ISG15 was related to RIG-I-like receptor signaling pathway, while CXCL10 was involved in both of the two pathways. Whereas, the down-regulated DEG, CXCL12 was significantly associated with axon guidance pathway. Additionally, these DEGs were also pivotal nodes in the PPI network with high degrees. Besides, CXCL10 and CD80 were both interacted with IFNG. The mRNA expression of ISG15 was obviously enhanced in human breast cancer cells MCF-7, while no significant difference of CXCL10 mRNA level was found between MCF10A and MCF-7 cells. Moreover, the proteins expression levels of CD80 and ISG15 were significantly increased in MCF-7, MDA-MB-468 and MDA-MB-231 breast cancer cells than in normal MCF10A cells. CD80 might be responsible for the breast cancer's progression and metastasis via regulating innate immune system. In addition, ISG15 is identified as a crucial gene signature associated with breast cancer development and metastasis via RIG-I-like receptor signaling pathway.

https://ift.tt/2SYuO4Q

Serum Vitamin D Binding Protein Level Associated with Metabolic Cardiovascular Risk Factors in Women with the Polycystic Ovary Syndrome

Horm Metab Res
DOI: 10.1055/a-0759-7533

The objective of the study was to measure the levels of 25-hydroxyvitamin D [25(OH)D] and vitamin D binding protein (VDBP) and assess their relationships with cardiovascular risk factors in women with the polycystic ovary syndrome (PCOS). A group of 267 women, aged 20–35 years (24.7 ± 4.9): 167 with PCOS and 100 healthy women were divided according to body mass index. Biochemical and hormonal parameters were measured. Free and bioavailable 25(OH)D were calculated using the mathematical equations. The percentage of body fat and visceral fat deposit were assessed by DXA. In the normal weight control group total, free, bioavailable 25(OH)D (p<0.001 for all) were significantly higher than in its overweight/obese counterpart, while VDBP levels were comparable. In PCOS women total 25(OH)D (p<0.001), and VDBP (p –0.006) were lower in the overweight/obese subgroups than in the normal weight ones. In both groups serum VDBP levels correlated negatively with serum insulin and positively with sex hormone binding globulin. In PCOS group, in contrast to control group, VDPB was negatively correlated with abdominal fat deposit, BMI, fasting glucose and positively with HDL. Despite lower total 25(OH)D in obese PCOS women, all women with PCOS (lean and obese) had comparable free and bioavailable 25(OH)D, which might be a result of concomitantly lowered serum VDBP levels in obese PCOS women. VDBP might play important role in the regulation of availability of active fractions of 25(OH)D in PCOS women. VDBP seems to be associated with cardiovascular risk factors such as BMI, waist circumference, visceral fat, and fasting serum insulin in women with PCOS.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

https://ift.tt/2Dui5Cx

Circulating cytokines predict immune-related toxicity in melanoma patients receiving anti-PD-1-based immunotherapy

Purpose: Combination PD-1 and CTLA-4 inhibitor therapy has dramatically improved the survival of patients with advanced melanoma but is also associated with significant immune-related toxicities. This study sought to identify circulating cytokine biomarkers of treatment response and immune-related toxicity. Experimental Design: The expression of 65 cytokines was profiled longitudinally in 98 melanoma patients treated with PD-1 inhibitors, alone or in combination with anti-CTLA-4, and in an independent validation cohort of 49 patients treated with combination anti-PD-1 and anti-CTLA-4. Cytokine expression was correlated with RECIST response and immune-related toxicity, defined as toxicity that warranted permanent discontinuation of treatment and administration of high dose steroids. Results: Eleven cytokines were significantly upregulated in patients with severe immune-related toxicities at baseline and early during treatment. The expression of these eleven cytokines was integrated into a single toxicity score, the CYTOX score, and the predictive utility of this score was confirmed in the discovery and validation cohorts. The area under the curve for the CYTOX score in the validation cohort was 0.68 at PRE (95% CI, 0.51-0.84, p=0.037) and 0.70 at EDT (95% CI, 0.55-0.85, p=0.017) using receiver operating characteristic (ROC) analysis. Conclusions:The CYTOX score is predictive of severe immune-related toxicity in melanoma patients treated with combination anti-CTLA-4 and anti-PD-1 immunotherapy. This score, which includes pro-inflammatory cytokines such as IL-1a, IL-2 and IFNa2, may help in the early management of severe, potentially life-threatening immune-related toxicity.

https://ift.tt/2RHPsVu

IND-enabling studies for a clinical trial to genetically program a persistent cancer-targeted immune system

Purpose: To improve persistence of adoptively transferred T cell receptor (TCR)-engineered T cells and durable clinical responses, we designed a clinical trial to transplant genetically-modified hematopoietic stem cells (HSCs) together with adoptive cell transfer (ACT) of T cells both engineered to express an NY-ESO-1 TCR. Here, we report the preclinical studies performed to enable an investigational new drug (IND) application. Experimental design: HSCs transduced with a lentiviral vector expressing NY-ESO-1 TCR and the PET reporter/suicide gene HSV1-sr39TK and T cells transduced with a retroviral vector expressing NY-ESO-1 TCR were co-administered to myelodepleted HLA-A2/K^b mice within a formal GLP-compliant study to demonstrate safety, persistence and HSC differentiation into all blood lineages. Non-GLP experiments included assessment of transgene immunogenicity and in vitro viral insertion safety studies. Furthermore, GMP-compliant cell production qualification runs were performed to establish the manufacturing protocols for clinical use. Results: TCR genetically-modified and ex vivo cultured HSCs differentiated into all blood subsets in vivo after HSC transplantation, and co-administration of TCR-transduced T cells did not result in increased toxicity. The expression of NY-ESO-1 TCR and sr39TK transgenes did not have a detrimental effect on gene-modified HSCs differentiation to all blood cell lineages. There was no evidence of genotoxicity induced by the lentiviral vector. GMP batches of clinical-grade transgenic cells produced during qualification runs had adequate stability and functionality. Conclusion: Co-administration of HSCs and T cells expressing an NY-ESO-1 TCR is safe in preclinical models. The results presented in this manuscript led to the U.S. FDA approval of IND 17471.

https://ift.tt/2DwV4iz

Pembro Ups Survival in PD-L1-positive HNSCC [News in Brief]

Subset of patients experiences deep and durable responses with first-line immunotherapy.

https://ift.tt/2qD7Cw2

New Classification for Myeloproliferative Neoplasms [News in Brief]

Sequencing analysis identifies disease subtypes; statistical models accurately predict outcomes.

https://ift.tt/2FcTO5L

Efficacy, Safety, and Biomarkers of Response to Azacitidine and Nivolumab in Relapsed/Refractory Acute Myeloid Leukemia: A Non-randomized, Open-label, Phase 2 Study [Research Articles]

Background: Preclinical models showed that blocking PD-1/PD-L1 pathways enhanced anti-leukemic responses. Azacitidine up-regulates PD-1 and interferon-gamma signaling. Methods: In this single arm trial, patients with relapsed/refractory (R/R) AML were treated with azacitidine 75mg/m2 Days 1-7 intravenously/subcutaneously with nivolumab 3mg/kg intravenously on Day 1 and 14, every 4-6 weeks. Findings: Seventy-patients were treated. The median age was 70-years (range,22-90). The median number of prior therapies was 2 (range,1-7). The overall response rate (ORR) was 33% including 15 (22%) complete remission (CR)/complete remission with insufficient recovery of counts (CRi), 1 partial response, and 7 patients with hematologic improvement (HI) maintained >6 months. Six-patients (9%) had stable disease >6 months. The ORR was 58% and 22%, in HMA-naive (n=25) and HMA pre-treated (n=45) patients, respectively. Grade 3-4 immune-related adverse events occurred in 8 (11%) patients. Pretherapy bone marrow and peripheral blood CD3 and CD8 were significantly predictive for response on flow-cytometry. CTLA-4 was significantly up-regulated on CD4+Teff in non-responders after 2 and 4 doses of nivolumab. Interpretation: Azacitidine-nivolumab therapy produced an encouraging response rate and overall survival in patients with R/R-AML, particularly in HMA-naive and Salvage-1 patients. Pretherapy bone marrow aspirate and peripheral blood CD3 percentage may be biomarkers for patient selection.

https://ift.tt/2qAtCb5

Reply to ‘Comment on ‘Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis”

Reply to 'Comment on 'Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis"

Reply to 'Comment on 'Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis", Published online: 09 November 2018; doi:10.1038/s41416-018-0247-y

Reply to 'Comment on 'Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis"

https://ift.tt/2JRGItd

Improving clinical diagnosis of early-stage cutaneous melanoma based on Raman spectroscopy

Improving clinical diagnosis of early-stage cutaneous melanoma based on Raman spectroscopy

Improving clinical diagnosis of early-stage cutaneous melanoma based on Raman spectroscopy, Published online: 09 November 2018; doi:10.1038/s41416-018-0257-9

Improving clinical diagnosis of early-stage cutaneous melanoma based on Raman spectroscopy

https://ift.tt/2qz92Yw

Prolyl-4-hydroxylase Α subunit 2 (P4HA2) expression is a predictor of poor outcome in breast ductal carcinoma in situ (DCIS)

Prolyl-4-hydroxylase Α subunit 2 (P4HA2) expression is a predictor of poor outcome in breast ductal carcinoma in situ (DCIS)

Prolyl-4-hydroxylase Α subunit 2 (P4HA2) expression is a predictor of poor outcome in breast ductal carcinoma in situ (DCIS), Published online: 09 November 2018; doi:10.1038/s41416-018-0337-x

Prolyl-4-hydroxylase Α subunit 2 (P4HA2) expression is a predictor of poor outcome in breast ductal carcinoma in situ (DCIS)

https://ift.tt/2F9BJ8I

Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b

Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b

Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b, Published online: 09 November 2018; doi:10.1038/s41416-018-0331-3

Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b

https://ift.tt/2JRGIcH

Comment on 'Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis'

Comment on 'Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis'

Comment on 'Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis', Published online: 09 November 2018; doi:10.1038/s41416-018-0237-0

Comment on 'Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis'

https://ift.tt/2ATFJFW

Trump Administration Finalizes Birth Control Coverage Opt-Out

THURSDAY, Nov. 8, 2018 -- A birth control coverage opt-out for employers was finalized by the Trump administration on Wednesday. The policy change means some employers with religious or moral objections will not have to provide no-cost birth control...

https://ift.tt/2RGBL9l

Firearm Violence Is a Public Health Issue, Physicians Say

THURSDAY, Nov. 8, 2018 -- In a position paper published online Oct. 30 in the Annals of Internal Medicine, the American College of Physicians (ACP) has updated its policy recommendations for reducing gun-related injuries and deaths in the United...

https://ift.tt/2DuzsTB

CDC: Increases in Yoga, Meditation for Children in 2012-2017

THURSDAY, Nov. 8, 2018 -- The use of yoga and meditation have increased in recent years among children and adults, while use of chiropractors has also increased among adults, according to two November data briefs published by the U.S. Centers for...

https://ift.tt/2RJTrki

CDC Warns of Salmonella Illnesses Linked to Raw Turkey

THURSDAY, Nov. 8, 2018 -- The total number of illnesses in a Salmonella outbreak linked with raw turkey products now stands at 164 people across 35 states, according to the U.S. Centers for Disease Control and Prevention. That number includes 74...

https://ift.tt/2DyaoeC

FDA Approves New Version of OTC Primatene Mist

THURSDAY, Nov. 8, 2018 -- A new version of an over-the-counter asthma inhaler that was taken off the market in 2011 has been approved by the U.S. Food and Drug Administration. U.S. sales of Primatene Mist were halted because it contained...

https://ift.tt/2RJe9kp

Systematic review: the consequences of psychosocial effects of inflammatory bowel disease on patients′ reproductive health

Summary

Background

High levels of voluntary childlessness and pregnancy‐related fears have been reported amongst inflammatory bowel disease (IBD) patients.

Aims

To investigate what factors determine IBD patients' childbearing decisions; and to examine psychosocial consequences of IBD on various aspects of patients' reproductive health.

Methods

Six electronic databases were searched in a pre‐specified and structured manner.

Results

A total of 41 articles with data on 7122 patients were included. Between one‐fifth to one‐third of IBD patients had chosen voluntary childlessness. Around 50% of all IBD patients have poor knowledge of pregnancy‐related issues in IBD. Poor knowledge of pregnancy‐related issues in IBD was associated with voluntary childlessness. Observational studies have found preconception counselling is associated with patients choosing parenthood. Pregnancy‐related fears and concerns are multifaceted, stemming partly from lack of knowledge of pregnancy‐related issues in IBD. Many female patients are considered at increased risk for pregnancy because between one‐fifth to one‐third of patients do not use contraception. Research evidence for sexual dysfunction after disease diagnosis and treatment is inconsistent. There are limited data on patients' pregnancy, postpartum and parenting experiences. A few shortcomings of the literature are evident; sample sizes were small, participation rates were low, use of non‐validated questionnaires was common, and few studies included men and/or ethnic minority groups. The design of intervention studies is also weak.

Conclusion

This review recommends pre‐conception counselling for all IBD patients of childbearing age to tackle poor knowledge and allow patients to make an informed decision on their reproductive health.

https://ift.tt/2QzwBvT

MicroRNA Expression in Focal Nodular Hyperplasia in Comparison with Cirrhosis and Hepatocellular Carcinoma

Abstract

The liver disease focal nodular hyperplasia (FNH) has several histological features that resemble hepatic cirrhosis. Since cirrhosis may develop further into hepatocellular carcinoma (HCC) contrary to FNH, the aim of the present study was to identify microRNAs (miRNA), which, by their altered expression levels, may be associated with the benign, tumor-like nature of FNH. Altogether 106 surgically removed formalin-fixed paraffin-embedded liver samples were selected, including 22 FNH, 45 cirrhosis, 24 HCC and 15 normal liver tissues. Etiology of the cases of cirrhosis and HCC includes hepatitis C and alcoholism and the HCC cases developed in cirrhotic livers. Relative expression levels of 14 miRNAs were determined using TaqMan MicroRNA Assays. In comparison to normal liver, the levels of miR-34a and miR-224 were elevated not only in FNH but also in cirrhosis and HCC, while the expression of miR-17-5p, miR-18a and miR-210 was decreased in FNH. Further, the levels of miR-21 and miR-222 were increased in cirrhosis and HCC but were decreased in FNH and the expression of miR-17-5p, miR-18a, miR-195 and miR-210 was decreased in FNH as compared with cirrhosis and/or HCC. In conclusion, the elevation of miR-34a and miR-224 may be associated with both benign and malignant proliferative processes, nevertheless the increased expression of oncomiRs miR-21 and miR-222 in cirrhosis and HCC but not in FNH may be related to malignant processes of the liver. The decreased levels of miR-18a, miR-195 and miR-210 may further differentiate FNH from cirrhosis, reflecting the different pathogenesis of these two entities contrary to some histologically similar features.

https://ift.tt/2z1Cefp

All EMS providers deserve equal protection

Why it is time to do away with different rules for different providers under the Firefighter Bill of Rights

https://ift.tt/2JPYJYK

Hemosuccus Pancreaticus and Hematochezia — An Unusual Presentation of a Rare Disease

https://ift.tt/2z1zLS4

Dose De-escalation to Adalimumab 40 mg Every Three Weeks in Patients With Inflammatory Bowel Disease – a Multicenter, Retrospective, Observational Study

Data about the outcomes after adalimumab dose de-escalation in inflammatory bowel disease (IBD) are scarce.

https://ift.tt/2OwACPD

Spotlight: Cradlepoint features a cloud-managed 4G LTE in-vehicle router, creating a secure and reliable network for first responders.

Cradlepoint is committed to making sure first responders can rely on them to keep them connected and protected.

https://ift.tt/2FeTpj7

Oxygen-guided radiation therapy

This paper presents the first experimental demonstration that electron paramagnetic resonance oxygen image guided radiation therapy increases tumor control with hypoxic boost doses relative to well oxygenated tumor boosts of roughly the same volume in mouse fibrosarcoma models. This is the first demonstration of the effectiveness of targeting specific hypoxic tumor in mammalian systems.

https://ift.tt/2yYF8Bw

Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b

https://ift.tt/2zGuAXe

Prolyl-4-hydroxylase Α subunit 2 (P4HA2) expression is a predictor of poor outcome in breast ductal carcinoma in situ (DCIS)

https://ift.tt/2SW1nQY

Reply to ‘Comment on ‘Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis”

https://ift.tt/2zELaXF

Comment on 'Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis'

https://ift.tt/2SYAUSI

Improving clinical diagnosis of early-stage cutaneous melanoma based on Raman spectroscopy

https://ift.tt/2zEL42f

Correction to: Semivariogram and Semimadogram functions as descriptors for AMD diagnosis on SD-OCT topographic maps using Support Vector Machine

After publication, it was highlighted that the original publication [1] contained a spelling mistake in the first name of Marcelo Gattas. This was incorrectly captured as Marelo Gattass in the original article...

https://ift.tt/2DaqaLF

Effect of Prophylaxis for Early Adrenal Insufficiency Using Low-Dose Hydrocortisone in Very Preterm Infants: An Individual Patient Data Meta-Analysis

To assess the effect of prophylaxis for early adrenal insufficiency using low-dose hydrocortisone on survival without bronchopulmonary dysplasia (BPD) in very preterm infants using an individual patient data meta-analysis.

https://ift.tt/2RLGCWU

Variability of Tidal Breathing Parameters in Preterm Infants and Associations with Respiratory Morbidity during Infancy: A Cohort Study

To test whether low variability of tidal volume (VT) and capnographic indices are predictive of subsequent respiratory morbidity in preterm infants.

https://ift.tt/2SYt4bK

An adult autosomal recessive chronic granulomatous disease patient with pulmonary Aspergillus terreus infection

Genetic mutations that reduce intracellular superoxide production by granulocytes causes chronic granulomatous disease (CGD). These patients suffer from frequent and severe bacterial and fungal infections thro...

https://ift.tt/2OAQjp4

The Majority of Piriformis Muscles are Innervated by the Superior Gluteal Nerve

INTRODUCTION

The piriformis muscle is clinically implicated in pain disorders, posterior approaches for total hip arthroplasty, and iatrogenic injury to the muscle and the surrounding nerves. The piriformis muscle has been said to receive innervation from L5 to S3 ventral rami with most sources using S1 and S2 ventral rami as the most common innervation this muscle. However, descriptions of the nerve in the literature are vague. Therefore, the aim of this study was to clarify the anatomy of the nerve supply to the piriformis muscle.

MATERIALS AND METHODS

Twenty sides from ten fresh‐frozen cadavers were studied. Specifically, via anterior dissection of the sacral plexus, branches to the piriformis were identified. Once identified, the nerves to the piriformis muscle were traced proximally to clarify their origin.

RESULTS

Nerves supplying the piriformis muscle existed on all sides. On 80% of sides, the piriformis was innervated by two to three nerves. The origin of these nerves was from the superior gluteal nerve on 14 sides (70%), inferior gluteal nerve on one side (5%), L5 ventral ramus on one side (5%), S1 ventral ramus on 17 sides (85%), and S2 ventral ramus on 14 sides (70%), respectively.

CONCLUSIONS

The most common nerve branches to the piriformis are from the superior gluteal nerve, and the ventral rami of S1 and S2. Based on our study, a single 'nerve to piriformis' does not exist in the majority of specimens thus this term should be abandoned.

This article is protected by copyright. All rights reserved.

https://ift.tt/2PmyBL9

The structural biology of the shelterin complex

Journal Name: Biological Chemistry
Issue: Ahead of print


https://ift.tt/2ATzhir

Reproducible dsRNA Microinjection and Oviposition Bioassay in Mosquitoes and House Flies

This protocol describes a microinjection methodology that we have standardized and used for several years to deliver specific quantities of nucleic acids directly to the hemolymph of mosquitoes and house flies. This protocol results in minimal injection mortality and allows dose correlated measurements of fecundity.

https://ift.tt/2T2fsMW

HPTLC Analysis of Solanum xanthocarpum Schrad. and Wendl., a Siddha Medicinal Herb

In the present study, HPTLC is used to detect the presence and amount of triterpenoids and phytosterols in different plant parts (fruit, stem, leaf, and root) of Solanum xanthocarpum Schrad. and Wendl.; such analysis is done for the first time. Each plant part has its own medicinal value and is used as Siddha medicinal herb. The employed statistical analysis ensures that the developed method is reproducible and selective. The results show that the fruit samples contain highest amount of tested phytochemicals. This method can be used as an important tool to ensure the therapeutic dose in herbal formulations, standardization, and quality control of bulk drugs.

https://ift.tt/2zDEHfD

Should antibiotic prophylaxis before orthopedic implant surgery depend on the duration of pre-surgical hospital stay?

Prolonged hospital stay before surgery is a risk for colonization with antibiotic-resistant microorganisms and possible antibiotic-resistant surgical site infections (SSI), which lacks acknowledgement in inter...

https://ift.tt/2QuiVSP

Keeping hospitals clean and safe without breaking the bank; summary of the Healthcare Cleaning Forum 2018

Keeping hospitals clean is a crucial patient safety issue. The importance of the hospital environment in patient care has only recently been recognized widely in infection prevention and control (IPC). In orde...

https://ift.tt/2PhPlmF

Correction to: Candidemia in a major regional tertiary referral hospital – epidemiology, practice patterns and outcomes

The original article [1] contains an error whereby the author, Pui Lai Rachel Ee's name is incorrectly presented.

https://ift.tt/2QuI3bO

Detection of an amplification bias associated to Leuconostocaceae family with a universal primer routinely used for monitoring microbial community structures within food products

Sequencing of 16S rDNA V3–V4 region is widely applied for food community profiling. However, two different universal forward primers (named here MUYZER-primer1 and KLINDWORTH-primer2) targeting an identical co...

https://ift.tt/2JNtdKX

Bacterial profile, antibiotic susceptibility pattern and associated factors among pregnant women with Urinary Tract Infection in Goba and Sinana Woredas, Bale Zone, Southeast Ethiopia

Urinary tract infection (UTI) is one of the commonest infections affecting millions worldwide, especially pregnant women. It can lead to poor maternal and perinatal outcomes. Untreated UTI can be associated wi...

https://ift.tt/2AUsvsB

Self-care practices and associated factors among diabetes patients attending the outpatient department in Bahir Dar, Northwest Ethiopia

The aim of this study was to assess diabetes self-care practice and associated factors among diabetes patients attending Felege-Hiwot Referral Hospital, Bahir Dar, Northwest Ethiopia.

https://ift.tt/2JRboKY

Vitamin D levels in a pediatric population of a primary care centre: a public health problem?

Vitamin D deficiency is a public health problem that occurs more frequently than expected. The aim of this study is to evaluate the vitamin D levels of children attending the paediatrics unit of the Bertamirán...

https://ift.tt/2ASKbVp

Correction to: Prevalence, antimicrobial susceptibility profile and predictors of asymptomatic bacteriuria among pregnant women in Adigrat General Hospital, Northern Ethiopia

Following publication of the original article [1], the authors reported that one of the authors' names was spelled incorrectly. In this Correction the incorrect and correct author name are shown. The original ...

https://ift.tt/2JPaHC5

ASO Author Reflections: Recurrence Predictors in Mucinous Appendiceal Tumors

https://ift.tt/2AUJFX7

An Overview of Bundled Payments for Surgical Oncologists: Origins, Progress to Date, Terminology, and Future Directions

https://ift.tt/2JPI7QR

ASO Author Reflections: Tailoring of Targeted Axillary Dissection—Intraoperative Nodal Evaluation Reduces Second Operations

https://ift.tt/2AUlwQw

ASO Author Reflections: The Future of Isolated Limb Perfusion

https://ift.tt/2JPABpg

ASO Author Reflections: Low-Volume Sentinel Node Disease After Neoadjuvant Chemotherapy is Still an Indication for Axillary Dissection

https://ift.tt/2ATVQ6B

Evidence for neurogenic inflammation in lichen planopilaris and frontal fibrosing alopecia pathogenic mechanism

Abstract

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are lymphocytic scarring alopecias affecting primarily the scalp. Although both diseases may share some clinical and histopathological features, in the last decade, FFA has become an "epidemic" particularly in Europe, North and South America with unique clinical manifestations compared to LPP, thus, raising the idea that this disease may have a different pathogenesis. Symptoms such as scalp burning, pruritus, or pain are usually present in both diseases, suggesting a possible role for nerves and neuropeptides in the pathogenesis of both diseases. Based on some previous studies, neuropeptides, such as substance P (SP) and calcitonin gene‐related peptide (CGRP), have been associated with lipid metabolism and many chronic inflammatory disorders. In this study we asked if these neuropeptides are associated with LPP and FFA scalp lesions. Alteration in the expression of SP and CGRP in affected and unaffected scalp skin from patients with both diseases was found with examination of sections using immunohistochemical techniques and confocal microscopy. We then quantitatively assessed and compared SP and CGRP expression from control, LPP and FFA scalp biopsies. Although LPP and FFA share similar histopathologic findings, opposite results were found in affected and unaffected scalp in the ELISA tests, suggesting that these diseases may have different pathogenic mechanisms. We also found presence of histopathological inflammation irrespective of evident clinical lesions, which raises the possibility that both diseases may be more generalized processes affecting the scalp.

This article is protected by copyright. All rights reserved.

https://ift.tt/2FebbTP

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next‐generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non‐BRCA1/2 gene. Major mutant non‐BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non‐BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER‐2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non‐BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non‐BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.

https://ift.tt/2qx4amO

Feasibility and acceptability of a proposed trial of acupuncture as an adjunct to lifestyle interventions for weight loss in Polycystic Ovary Syndrome: a qualitative study

Polycystic Ovary Syndrome (PCOS) is a common female reproductive disorder with multiple manifestations. Weight management is a key therapeutic goal. Acupuncture is a potential adjunctive weight loss treatment ...

https://ift.tt/2Dwq16v

The actual conditions of traditional Japanese Kampo education in all the pharmacy schools in Japan: a questionnaire survey after the enforcement of the new national 2015 core curriculum

To investigate the present status of Kampo education, which has still not been elucidated, after the introduction of the new core national curriculum of 2015 into nationwide pharmacy education, in all 74 pharm...

https://ift.tt/2RLwCgk

A Micro-CT-based Method for Characterizing Lesions and Locating Electrodes in Small Animal Brains

This article describes a straightforward method to prepare small animal brains for micro-CT imaging, in which lesions can be quantified and electrodes located with high precision in the context of the whole brain.

https://ift.tt/2PKA11w

High Frequency Ultrasound for the Analysis of Fetal and Placental Development In Vivo

Here we describe the technique of high frequency ultrasound for in vivo analysis of fetuses in mice. This method allows the follow-up of fetuses and the analysis of placental parameters as well as maternal and fetal blood flow throughout pregnancy.

https://ift.tt/2DaQjdl

Eight Factors May Link Disparities in Cancer Death Rates and Income

Eight factors may explain more than 80% of the relationship between poverty and disparities in cancer death rates at the county level, according to a new study. The largest mediator was a surprise to the researchers.

https://ift.tt/2STMdvA

3 ways to improve your community paramedicine program

Brought to you by Medline Amidst rising costs and dramatic changes to healthcare reimbursements, the entire system has been tasked with discovering new and effective means to prevent and manage chronic health conditions. Throughout the country, Community Paramedicine programs have proven effective, providing follow-up care, education, and referrals when additional resources are needed. At home...

https://ift.tt/2QvgXkY

Get an edge in EMS: Protect your staff, patients and business

Medline's presence at EMS World marked by unique insights for opioid crisis and budget issues. As thousands of emergency medical services professionals converge on Nashville, Tenn., Medline EMS will be at the 2018 EMS World Expo to help them keep up with the constant changes and demands of the industry. Along with solutions for revenue, patient care, and cost savings at the Medline EMS...

https://ift.tt/2yYja1H

My burning issues in neuroendocrine tumours (NET)

Summary

Several compounds have recently been approved for the systemic treatment of advanced well-differentiated neuroendocrine tumours (NET) of gastroenteropancreatic (GEP) or lung origin. Based on the PROMID and CLARINET trials, somatostatin analogues (SSA) are the preferred first-line approach for all GEP-NET and offer—in addition to antiproliferative effects—durable symptomatic relief for hormonally active tumours. The mTOR inhibitor everolimus has been approved for progressive GEP- and lung-NET and is a widely used drug in this setting. Furthermore, recent results have underlined the high efficacy of somatostatin-receptor targeting radionuclide therapy (PRRT) in somatostatin-receptor positive midgut tumours and PRRT is now considered standard treatment for midgut-NET progressing on SSA. The optimal application of PRRT in somatostatin receptor positive NET with non-midgut site is currently an issue of discussion and should be decided on an individually basis in multidisciplinary boards. Following new insights in the genetic landscape of NET, "hot topics" in recent months include optimal treatment of the recently defined NET G3 and preliminary data on immunotherapy.

https://ift.tt/2Pg221w

The impact of surgery in oligometastatic prostate cancer

Summary

Oligometastatic prostate cancer has been considered an intermediate state between localized disease and widespread metastases, but there is no consensus on the definition of oligometastasis in prostate cancer. At present, a clinical diagnosis made on the basis of up to five extrapelvic lesions is reasonable for use. Retrospective studies and post hoc analyses suggest that local or metastasis-directed interventions could have benefits in the oligometastatic state including a better response to systematic therapy, lower risk of local complications, and possible positive impact on cancer-specific survival and overall survival; however, insufficient data are available to draw reliable conclusions. In this short review, we summarize the current available data on the role of surgery in oligometastatic prostate cancer.

https://ift.tt/2QupLrt

Improved Long-Term Pregnancy Outcomes for Goserelin + Chemo

THURSDAY, Nov. 8, 2018 -- For premenopausal women with stage I to IIIA estrogen receptor-negative, progesterone receptor-negative breast cancer, goserelin plus chemotherapy is associated with an increased likelihood of becoming pregnant without an...

https://ift.tt/2Oz0jiq

Quantity of Opioids Prescribed Postop Linked to Consumption

THURSDAY, Nov. 8, 2018 -- The quantity of opioids prescribed after surgery is associated with patient-reported opioid consumption, according to a study published online Nov. 7 in JAMA Surgery. Ryan Howard, M.D., from the University of Michigan in...

https://ift.tt/2OwegxT

Herpes Zoster Recombinant Vaccine Seems Most Effective

THURSDAY, Nov. 8, 2018 -- The herpes zoster adjuvant recombinant subunit vaccine may be more effective than the live attenuated vaccine, though it is associated with an increased risk for adverse events at the injection site, according to a review...

https://ift.tt/2yWv3oM

hs-cTnI Can Rule Out Inducible Myocardial Ischemia in CAD

THURSDAY, Nov. 8, 2018 -- For patients with stable coronary artery disease (CAD), very low levels of resting high-sensitivity cardiac troponin I (hs-cTnI) can rule out inducible myocardial ischemia, according to a study published online Nov. 6 in...

https://ift.tt/2yYoeTL

Concussion-Related Biomarkers Vary Based on Sex, Race

THURSDAY, Nov. 8, 2018 -- Concussion-related serum biomarkers vary by sex and race, which may complicate their interpretation, according to three studies published online Nov. 7 in Neurology. Breton M. Asken, from the University of Florida in...

https://ift.tt/2OzuIgz

Zoliflodacin Seems Effective for Some Gonococcal Infections

THURSDAY, Nov. 8, 2018 -- Oral zoliflodacin, which inhibits DNA biosynthesis, seems effective for urogenital and rectal gonococcal infections but is less effective for pharyngeal infections, according to a study published in the Nov. 8 issue of the...

https://ift.tt/2z1062L

In-Hospital Infection May Up Readmission After Stroke

THURSDAY, Nov. 8, 2018 -- For patients with ischemic stroke, infection during stroke hospitalization is associated with increased odds of 30-day readmission, according to a study published online Nov. 1 in Stroke. Amelia K. Boehme, Ph.D., from...

https://ift.tt/2yZznn7

Quitting Cannabis Tied to Improved Memory

THURSDAY, Nov. 8, 2018 -- Abstaining from cannabis is associated with improvements in memory and verbal learning in adolescents and young adults, according to a study published online Oct. 30 in the Journal of Clinical Psychiatry. Randi Melissa...

https://ift.tt/2OyNtAV

Nurses With Bachelor's Degree Feel More Prepared

THURSDAY, Nov. 8, 2018 -- The number of quality and safety educational gaps between nurses with bachelor's and associate degrees has substantially increased since 2007 to 2008, according to a study published online Oct. 24 in the Joint Commission...

https://ift.tt/2OsnHyh

Use of Polyetheretherketone Devices May Up Pseudarthrosis

THURSDAY, Nov. 8, 2018 -- For one-level anterior cervical discectomy and fusion (ACDF), use of polyetheretherketone (PEEK) devices is associated with significantly higher rates of radiographically demonstrated pseudarthrosis and need for revision...

https://ift.tt/2z2kP6a

Desumoylating Isopeptidase 2 (DESI2) Inhibits Proliferation and Promotes Apoptosis of Pancreatic Cancer Cells through Regulating PI3K/AKT/mTOR Signaling Pathway

Abstract

This study aimed to investigate the effects of desumoylating isopeptidase 2 (DESI2) on tumor cell proliferation, apoptosis and invasion of pancreatic cancer, and to assess the signaling pathway involved. Overexpression and silence of DESI2 were designed and the experiments were divided into 5 groups: a normal control group, an interference control group (shRNA-NC); an interference group (sh-DESI2); an overexpression control group (NC), an overexpression group (DESI2). Quantitative real time polymerase chain reaction (qRT-PCR) was used to screen the appropriate interference sequence. The silencing and overexpression of DESI2 were confirmed by qRT-PCR and western blotting. Cell cycling, apoptosis, invasion, and the expression of phosphatidylinositol-3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway and caspase 3 were measured. Overexpression and silence of DESI2 were successfully designed in two pancreatic cancer cells, and the interference effect of sh-DESI2–3 showed the best silencing effects. The biological activities of DESI2 were detected in both ASPC-1 and PANCE-1 cells. Our results showed that cell proliferation was significantly increased in the sh-DESI2 group, while decreased in DESI2 group compared with the control group in both cell lines. In ASPC-1 cells, the events in G1 phase decreased and in S phase increased obviously in the sh-DESI2 group, compared with control group. An opposite result was found when DESI2 was overexpressed. In PANCE-1 cells, the events in G2 phase were higher in the sh-DESI2 group, while in the DESI2 group was significantly lower than that in control group. In ASPC-1 and PANCE-1 cells, sh-DESI2 group showed decreased apoptosis, increased cell invasion and increased expression of AKT, p-Akt, PI3K, p-PI3K, p-mTOR and mTOR and decreased caspase 3 expression compared with the control group, while overexpression of DESI2 leaded to increased apoptosis, decreased cell invasion and reduced expression of AKT, p-Akt, PI3K, p-PI3K, p-mTOR and mTOR and increased expression of caspase 3. DESI2 regulates the proliferation and apoptosis of pancreatic cancer cells through PI3K/AKT/mTOR signaling pathway.

https://ift.tt/2qAK2jy

Microdialysis of Excitatory Amino Acids During EEG Recordings in Freely Moving Rats

Here, we describe a method for in vivo microdialysis to analyze aspartate and glutamate release in the ventral hippocampus of epileptic and non-epileptic rats, in combination with EEG recordings. Extracellular concentrations of aspartate and glutamate may be correlated with the different phases of the disease.

https://ift.tt/2Fbk1RY

Using the FishSim Animation Toolchain to Investigate Fish Behavior: A Case Study on Mate-Choice Copying In Sailfin Mollies

Using the novel FishSim Animation Toolchain, we present a protocol for non-invasive visual manipulation of public information in the context of mate-choice copying in sailfin mollies. FishSim Animation Toolchain provides an easy-to-use framework for the design, animation and presentation of computer-animated fish stimuli for behavioral experiments with live test fish.

https://ift.tt/2qBLP7X

Comprehensive Lateral Neck Dissection in Papillary Thyroid Carcinoma may Reduce Lateral Neck Recurrence Rates

Abstract

Objective

To Identify predictors of recurrent disease following lateral neck dissection (LND) for papillary thyroid carcinoma (PTC).

Methods

A retrospective review of patients who underwent first-time LND for PTC at our institution (2000–2015) was performed. Medical records were examined for biopsy or pathologically proven lateral neck recurrence. Differences between the groups with and without recurrence were compared. All LNDs were then classified in to two groups: "comprehensive" (CND), involving levels IIa-Vb at minimum, or "selective", labelling less extensive dissection (SND).

Results

Four hundred nine patients underwent 467 LNDs. Surveillance data were available for 317 patients who underwent 362 LNDs (mean age 45 ± 16; range 18–88). The median follow-up was 64 ± 48 months (range 3–197). Recurrence was detected in 71 lateral necks (20%). The total number of lymph nodes was greater in the group without recurrence compared to those with recurrence (23 vs. 19, p = 0.02). Among patient demographics, radioactive iodine treatment, primary tumor characteristics and characteristics of nodal metastases, only an older patient age (mean 50 vs. 43 years) was associated with lateral neck recurrence (p < .01). CND was performed in 102 lateral necks and SND in 143 necks. There were 12 recurrences recorded in the CND group (12%) vs. 31 in the SND group (22%, p = .04). The majority of recurrences (70%) involved levels included in the original dissection.

Conclusions

Younger patients, more extensive dissection and a higher total number of lymph nodes removed are associated with a lower incidence of lateral neck recurrence after LND for papillary thyroid carcinoma.

https://ift.tt/2yYeDMy

MORC2 promotes development of an aggressive colorectal cancer phenotype through inhibition of NDRG1

Summary

MORC2 (microrchidia family CW‐type zinc finger 2) is a newly identified chromatin remodeling protein that functions in diverse biological processes including gene transcription. NDRG1 is a metastasis suppressor and a prognostic biomarker for colorectal cancer (CRC). However, the relationship between MORC2 and NDRG1 transcriptional regulation and the roles of MORC2 in CRC remain elusive. Here, we showed that MORC2 down‐regulated NDRG1 mRNA, protein levels and promoter activity in CRC cells. We also found that MORC2 bound to the –446~–213bp region of the NDRG1 promoter. Mechanistically, histone deacetylase SIRT1 was involved in NDRG1 transcriptional regulation. MORC2 was able to interact with SIRT1 and inhibit NDRG1 promoter activity cumulatively with SIRT1. MORC2 overexpression led to a decreasement of H3Ac and H4Ac of the NDRG1 promoter. Importantly, we demonstrated that NDRG1 was essential in MORC2‐mediated promotion of CRC cell migration and invasion in vitro, as well as lung metastasis of CRC cells in vivo. Moreover, MORC2 expression correlated negatively with NDRG1 expression in CRC patients. High expression of MORC2 was significantly associated with lymph node metastasis (p=0.019) and poor pTNM stage (p=0.02) and the expression of MORC2 correlated with poor prognosis in colon cancer patients. Our findings thus contribute to the knowledge of the regulatory mechanism of MORC2 in down‐regulating NDRG1, and suggest MORC2 as a potential therapeutic target for CRC.

This article is protected by copyright. All rights reserved.

https://ift.tt/2OxvieI