Cost Effectiveness of Intra-Articular Hyaluronic Acid and Disease-Modifying Drugs in Knee Osteoarthritis

Abstract

Background

The place of disease-modifying osteoarthritis drugs (DMOADs) and intra-articular hyaluronic acid (IAHA) in the therapeutic arsenal for knee osteoarthritis (OA) remains uncertain. Indeed, these treatments have demonstrated symptomatic efficacy but no efficacy for disease modification.

Objective

This report reviews the cost effectiveness of IAHA and DMOADs used in the treatment of knee OA.

Methods

A systematic literature search of the MEDLINE, Scopus, EMBASE and Cochrane databases was performed independently by two rheumatologists who used the same predefined eligibility criteria to identify relevant articles. Papers without abstracts and in languages other than English or French were excluded. Extracted costs were annualised and converted to 2015 euros (€) using the Consumer Price Index of the relevant countries and the 2013 Purchasing Power Parities between these countries and the European Union average.

Results

A total of 95 abstracts were selected, and 13 articles were considered for the review: nine articles on IAHA and four on DMOADs. Only one article directly compared different IAHA compounds. Articles showed substantial heterogeneity in methodological approaches. The incremental cost-effectiveness ratios (ICERs) ranged from €4000 to €57,550 and from €240 to €53,225 per quality-adjusted life-year (QALY) gained for DMOADs and IAHA, respectively.

Conclusions

This review highlights substantial heterogeneity between studies, ranging from a cost saving (or dominating) position to very high ICERs, far above the acceptability threshold of €50,000/QALY. Additional research is needed to determine reliable and robust ICER estimates for knee OA therapies.

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Utility Values for Health States in Ireland: A Value Set for the EQ-5D-5L

Abstract

Objective

Our objective was to develop a value set based on Irish utility values for the EuroQol 5-Dimension, 5-Level instrument (EQ-5D-5L).

Methods

The research design and data collection followed a protocol developed by the EuroQol Group. The EuroQol Valuation Technology (EQ-VT) software was administered using computer-assisted personal interviews to a representative sample of adults resident in Ireland between 2015 and 2016. Utility values were elicited using two stated-preference techniques: time trade-off (TTO) and discrete-choice experiment (DCE). Each respondent completed a valuation exercise in which the EQ-VT system randomly selected one block of ten TTO questions from ten blocks relating to a possible 86 health states. One block of seven DCE pairs from 28 blocks of a possible 196 pairs of health states were randomly selected to accompany this. The relationship between utility values and health states was analysed using a hybrid regression model that combined data from the TTO and DCE techniques and expressed these as a function of the health state presented to the individual. This model estimated coefficients for 20 dummy variables that characterised each health state in the EQ-5D-5L framework, with the lowest level of severity providing the reference category in each domain. The relationship between weighted and unweighted TTO and DCE analyses of main effects was analysed separately.

Results

Comparison of weighted and unweighted models revealed no substantive differences in results with respect to either DCE or TTO models. The unweighted hybrid model produced estimated effects, the ordering of which was intuitively consistent within each domain: lower levels of health were associated with lower utility values. Differences were evident between domains with respect to valuations; the disutility associated with conditions related to anxiety/depression and pain/discomfort was higher than for other domains. The decrement in utility associated with movement from the highest to the lowest level of health was 0.344 for mobility, 0.287 for self-care, 0.187 for usual activities, 0.510 for pain/discomfort and 0.646 for anxiety/depression.

Discussion

The results present the first value set based on the EQ-5D-5L framework for a representative sample of residents in Ireland. The set reveals a higher decrement in utility associated with anxiety/depression than with other domains of health. Caution is warranted in comparisons with other value sets. That said, those in England, the Netherlands, Uruguay and China reveal that, whereas Irish values are broadly consistent with respect to mobility, self-care and usual activities, residents of Ireland attach a higher decrement to pain/discomfort and anxiety/depression than do other populations.

https://ift.tt/2CukRHg

Nivolumab for Treating Metastatic or Unresectable Urothelial Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Abstract

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Bristol-Myers Squibb) of nivolumab (Opdivo^®) to submit evidence of its clinical and cost effectiveness for metastatic or unresectable urothelial cancer. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group (ERG), which produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based on the company's submission to NICE. Nivolumab was compared with docetaxel, paclitaxel, best supportive care and retreatment with platinum-based chemotherapy (cisplatin plus gemcitabine, but only for patients whose disease has had an adequate response in first-line treatment). Two ongoing, phase I/II, single-arm studies for nivolumab were identified, but no studies directly compared nivolumab with any specified comparator. Evidence from directly examining the single arms of the trial data indicated little difference between the outcomes measured from the nivolumab and comparator studies. A simulated treatment comparison (STC) analysis was used in an attempt to reduce the bias induced by naïve comparison, but there was no clear evidence that risk of bias was reduced. Multiple limitations in the STC were identified and remained. The effect of an analysis based on different combinations of covariates in the prediction model remains unknown. The ERG's concerns regarding the economic analysis included the use of a non-established response-based survival analysis method, which introduced additional uncertainty. The use of time-dependent hazard ratios produced overfitting and was not represented in the probabilistic sensitivity analysis. The use of a treatment stopping rule to cap treatment cost left treatment effectiveness unaltered. A relevant comparator was excluded from the base-case analysis. The revised ERG deterministic base-case incremental cost-effectiveness ratios based on the company's Appraisal Consultation Document response were £58,791, £78,869 and £62,352 per quality-adjusted life-year gained versus paclitaxel, docetaxel and best supportive care, respectively. Nivolumab was dominated by cisplatin plus gemcitabine in the ERG base case. Substantial uncertainties about the relative treatment effectiveness comparing nivolumab against all comparators remained. NICE did not recommend nivolumab, within its marketing authorisation, as an option for treating locally advanced, unresectable or metastatic urothelial carcinoma in adults who have had platinum-containing therapy, and considered that nivolumab was not suitable for use within the Cancer Drugs Fund.

https://ift.tt/2IEsvzb

Comparative cardio and developmental toxicity induced by the popular medicinal extract of Sutherlandia frutescens (L.) R.Br. detected using a zebrafish Tuebingen embryo model

Sutherlandia frutescens is one of the most promising commercialized, indigenous and medicinal plants of South Africa that is used as an immune-booster, and a traditional treatment for cancer. However, few studies...

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In order to ensure that evidence is unbiased it is sometimes necessary to retreat to the scientific ivory tower

https://ift.tt/2PcoR28

Sequential MRI in pontine and extrapontine myelinolysis following rapid correction of hyponatremia

This study describes the MRI changes associated with pontine and extrapontine myelinolysis secondary to rapid correction of hyponatremia in dogs. The authors discuss the relevance of the results for theories o...

https://ift.tt/2zUfRtg

A conditional Pax6 depletion study with no morphological effect on the adult mouse corneal epithelium

The corneas of heterozygous Pax6+/− mice develop abnormally and deteriorate further after birth but it is not known whether the postnatal deterioration is predetermined by abnormal development. Our objective was ...

https://ift.tt/2BYXSDq

Chemical crystal identification with deep learning machine vision

This study was carried out with the purpose of testing the ability of deep learning machine vision to identify microscopic objects and geometries found in chemical crystal structures.

https://ift.tt/2zVaM3K

Anemia and other hematological profiles of pregnant women attending antenatal care in Debre Berhan Referral Hospital, North Shoa, Ethiopia

The aim of the study was to determine level of anemia and other hematological profiles in pregnant women attending antenatal care clinic in Debre Berhan Referral Hospital, Ethiopia.

https://ift.tt/2BWnKQl

Evaluation of patient- versus provider-collected vaginal swabs for microbiome analysis during pregnancy

We aimed to evaluate if patient- and provider-collected vaginal swabs in pregnant women reflect similar bacterial community characteristics. Pregnant patients performed a self-collected vaginal swab, then unde...

https://ift.tt/2zVJuu6

Hydrogel coils versus bare platinum coils for the endovascular treatment of intracranial aneurysms: a meta-analysis of randomized controlled trials

Recent studies have shown conflicting results regarding the effect of hydrogel coils for treating intracranial aneurysm compared to bare platinum coils. We implemented a meta-analysis to assess the value of hy...

https://ift.tt/2y29Kl8

Massive citations to misleading methods and research tools: Matthew effect, quotation error and citation copying

https://ift.tt/2Ctno4x

Quality of diabetes care in breast, colorectal, and prostate cancer

Abstract

Purpose

Overlooking other medical conditions during cancer treatment and follow-up could result in excess morbidity and mortality, thereby undermining gains associated with early detection and improved treatment of cancer. We compared the quality of care for diabetes patients subsequently diagnosed with breast, colorectal, or prostate cancer to matched, diabetic non-cancer controls.

Methods

Longitudinal cohort study using primary care records from the Clinical Practice Research Datalink, United Kingdom. Patients with pre-existing diabetes were followed for up to 5 years after cancer diagnosis, or after an assigned index date (non-cancer controls). Quality of diabetes care was estimated based on Quality and Outcomes Framework indicators. Mixed effects logistic regression analyses were used to compare the unadjusted and adjusted odds of meeting quality measures between cancer patients and controls, overall and stratified by type of cancer.

Results

3382 cancer patients and 11,135 controls contributed 44,507 person-years of follow-up. In adjusted analyses, cancer patients were less likely to meet five of 14 quality measures, including: total cholesterol ≤ 5 mmol/L (odds ratio [OR] = 0.82; 95% confidence interval [CI], 0.75–0.90); glycosylated hemoglobin ≤ 59 mmol/mol (adjusted OR = 0.77; 95% CI, 0.70–0.85); and albumin creatinine ratio testing (adjusted OR = 0.83; 95% CI, 0.75–0.91). However, cancer patients were as likely as their matched controls to meet quality measures for other diabetes services, including retinal screening, foot examination, and dietary review.

Conclusions

Although in the short-term, cancer patients were less likely to achieve target thresholds for cholesterol and HbA1c, they continued to receive high-quality diabetes primary care throughout 5 years post diagnosis.

Implications for Cancer Survivors

These findings are important for cancer survivors with pre-existing diabetes because they indicate that high-quality diabetes care is maintained throughout the continuum of cancer diagnosis, treatment, and follow-up.

https://ift.tt/2Rv4Oxa

Multi-trait, Multi-environment Deep Learning Modeling for Genomic-Enabled Prediction of Plant Traits

Multi-trait and multi-environment data are common in animal and plant breeding programs. However, what is lacking are more powerful statistical models that can exploit the correlation between traits to improve prediction accuracy in the context of genomic selection (GS). Multi-trait models are more complex than univariate models and usually require more computational resources, but they are preferred because they can exploit the correlation between traits, which many times helps improve prediction accuracy. For this reason, in this paper we explore the power of multi-trait deep learning (MTDL) models in terms of prediction accuracy. The prediction performance of MTDL models was compared to the performance of the Bayesian multi-trait and multi-environment (BMTME) model proposed by Montesinos-López et al. (2016), which is a multi-trait version of the genomic best linear unbiased prediction (GBLUP) univariate model. Both models were evaluated with predictors with and without the genotype environment interaction term. The prediction performance of both models was evaluated in terms of Pearson's correlation using cross-validation. We found that the best predictions in two of the three data sets were found under the BMTME model, but in general the predictions of both models, BTMTE and MTDL, were similar. Among models without the genotype environment interaction, the MTDL model was the best, while among models with genotype environment interaction, the BMTME model was superior. These results indicate that the MTDL model is very competitive for performing predictions in the context of GS, with the important practical advantage that it requires less computational resources than the BMTME model.

https://ift.tt/2OI4AnU

Multi-environment Genomic Prediction of Plant Traits Using Deep Learners with Dense Architecture

Genomic selection is revolutionizing plant breeding and therefore methods that improve prediction accuracy are useful. For this reason, active research is being conducted to build and test methods from other areas and adapt them to the context of genomic selection. In this paper we explore the novel deep learning (DL) methodology in the context of genomic selection. We compared DL methods with densely connected network architecture to one of the most often used genome-enabled prediction models: Genomic Best Linear Unbiased Prediction (GBLUP). We used nine published real genomic data sets to compare a fraction of all possible deep learning models to obtain a "meta picture" of the performance of DL methods with densely connected network architecture. In general, the best predictions were obtained with the GBLUP model when genotypexenvironment interaction (GxE) was taken into account (8 out of 9 data sets); when the interactions were ignored, the DL method was better than the GBLUP in terms of prediction accuracy in 6 out of the 9 data sets. For this reason, we believe that DL should be added to the data science toolkit of scientists working on animal and plant breeding. This study corroborates the view that there are no universally best prediction machines.

https://ift.tt/2QxiXIX

Lost in Translation: Deciphering the mechanism of action of anti-human CTLA-4

Despite a number of pre-clinical studies demonstrating that the activity of anti-CTLA-4 antibodies in murine models of cancer relies on effector T cell activation and Treg depletion, the activity of the clinical antibodies remains controversial. To decipher such mechanisms is critical to the development of novel and more potent immunotherapies.

https://ift.tt/2y4qmZr

Implications of epigenetic drift in colorectal neoplasia

Many normal tissues undergo age-related drift in DNA methylation, providing a quantitative measure of tissue age. Here we identify and validate 781 CpG-islands (CGI) that undergo significant methylomic drift in 232 normal colorectal tissues and show that these CGI continue to drift in neoplasia while retaining significant correlations across samples. However, compared with normal colon, this drift advanced (~3-4 fold) faster in neoplasia, consistent with increased cell proliferation during neoplastic progression. The observed drift patterns were broadly consistent with modeled adenoma-carcinoma sojourn time distributions from colorectal cancer (CRC) incidence data. These results support the hypothesis that, beginning with the founder premalignant cell, cancer precursors frequently sojourn for decades before turning into cancer, implying that the founder cell typically arises early in life. At least 77-89% of the observed drift variance in distal and rectal tumors was explained by stochastic variability associated with neoplastic progression, while only 55% of the variance was explained for proximal tumors. However, gene-CGI pairs in the proximal colon that underwent drift were significantly and primarily negatively correlated with cancer gene expression, suggesting that methylomic drift participates in the clonal evolution of CRC. Methylomic drift advanced in colorectal neoplasia consistent with extended sojourn time distributions, which accounts for a significant fraction of epigenetic heterogeneity in CRC. Importantly, these estimated long-duration premalignant sojourn times suggest that early dietary and lifestyle interventions may be more effective than later changes in reducing CRC incidence.

https://ift.tt/2OEvLA4

Defective Nuclear Envelope Assembly May Promote Mitotic Errors [Research Watch]

Defective assembly of the nuclear envelope and nuclear pore complex in micronuclei may underlie chromothripsis.

https://ift.tt/2yi6l14

Better Standards Sought for Predictive Immunotherapy Biomarkers [News in Depth]

Initiatives aim to validate and harmonize assays that capture the inherent complexity of interactions between tumors and the immune system.

https://ift.tt/2RwlViu

Lurbinectedin Is Active in Patients with BRCA1/2 Mutant Breast Cancer [Research Watch]

A phase II trial evaluated lurbinectedin in patients with BRCA1/2-mutant and wild-type tumors.

https://ift.tt/2RwlOn4

Neutrophil Extracellular Traps Trigger Dormant Tumor Cell Proliferation [Research Watch]

Inflammation-induced neutrophil extracellular traps (NET) awaken dormant cells to promote metastasis.

https://ift.tt/2ygOmIn

CAR T-cell Therapy for Solid Tumors? [News in Depth]

Challenges abound, but researchers are investigating a variety of novel approaches.

https://ift.tt/2Rtfix4

An enhanced regimen as post-exposure chemoprophylaxis for leprosy: PEP++

The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-expo...

https://ift.tt/2O6J6Sl

Preoperative oral antibiotic prophylaxis reduces Pseudomonas aeruginosa surgical site infections after elective colorectal surgery: a multicenter prospective cohort study

Healthcare-associated infections caused by Pseudomonas aeruginosa are associated with poor outcomes. However, the role of P. aeruginosa in surgical site infections after colorectal surgery has not been evaluated....

https://ift.tt/2E2PoxP

Infectious Disease Emergencies

EMERGENCY MEDICINE CLINICS OF NORTH AMERICA

https://ift.tt/2CrALCk

Skin and Soft Tissue Infections in the Emergency Department

This article covers the diagnosis and treatment of skin and soft tissue infections commonly encountered in the emergency department: impetigo, cutaneous abscesses, purulent cellulitis, nonpurulent cellulitis, and necrotizing skin and soft tissue infections. Most purulent infections in the United States are caused by methicillin-resistant Staphylococcus aureus. For abscesses, we emphasize the importance of incision and drainage. Nonpurulent infections are usually caused by streptococcal species and initial empiric antibiotics need not cover methicillin-resistant Staphylococcus aureus. For uncommon but potentially lethal necrotizing skin and soft tissue infections, the challenge is rapid diagnosis in the emergency department and prompt surgical exploration and debridement.

https://ift.tt/2IENaTO

Infectious Disease Emergencies

For thousands of years, physicians have been battling infections. Infectious disease is likely responsible for more human deaths in history than any other cause, medical or nonmedical. In fact, it is said that mosquito-borne infections alone are responsible for more deaths than all of the wars in human history combined. For thousands of years, plagues and epidemics caused by infections have affected national leaders, armies, cultures, societies, and even world history. Some of the greatest physicians of recent centuries, including Lister, Jenner, Pasteur, Koch, Reed, and Ehrlich, made their mark via their discoveries that helped fight infections.

https://ift.tt/2Cu9XBk

Here to Stay: Infectious Diseases in Emergency Medicine

Infectious diseases are some of the most common reasons patients seek care in the emergency department (ED). While infection-related mortality in the United States has declined significantly over the past four decades, infectious diseases remain among the most frequently reported diagnoses for ED visits.1,2 Infectious diseases account for 13.5% of all ED visits among adults aged 65 years and older.3 The spectrum of infectious disease encountered in the practice of emergency medicine is dynamic and staggering, ranging from the commonplace (eg, community-acquired pneumonia) to the rare (eg, inhalation anthrax).

https://ift.tt/2IEEvRa

Copyright

ELSEVIER

https://ift.tt/2CuyeHJ

Contributors

AMAL MATTU, MD

https://ift.tt/2IHoTMY

Contents

Amal Mattu

https://ift.tt/2IFvurf

Emergency Department Approach to the Patient with Suspected Central Nervous System Infection

Central nervous system (CNS) infections require early recognition and aggressive management to improve patient survival and prevent long-term neurologic sequelae. Although early detection and treatment are important in many infectious syndromes, CNS infections pose unique diagnostic and therapeutic challenges. The nonspecific signs and symptoms at presentation, lack of characteristic infectious changes in laboratory and imaging diagnostics, and closed anatomic and immunologically sequestered space each present challenges to the emergency physician. This article proposes an approach to the clinical evaluation of patients with suspected CNS infection and highlights methods of diagnosis, treatment, and complications associated with CNS infections.

https://ift.tt/2CrALSQ

CME Accreditation Page

https://ift.tt/2IG0M1f

Forthcoming Issues

Ear, Nose, and Throat Emergencies

https://ift.tt/2Cvp4uH

Infective Endocarditis

Infective endocarditis (IE) is an uncommon infection of cardiac valves associated with bacteremia. It increasingly affects elderly patients with chronic disease and artificial cardiac devices. The presentation, however, remains subtle and varied, with nonspecific symptoms ranging from those resembling a mild viral infection to septic shock and multiorgan failure. IE carries potential to cause significant morbidity and mortality through its impact on cardiac function and from embolic complications. Blood cultures prior to antibiotics and obtaining prompt echocardiography are key diagnostic steps, followed by proper selection of empiric antibiotics and, in many cases, collaboration with infectious disease, cardiology, and cardiothoracic surgery specialists.

https://ift.tt/2IGPhGS

Natural regulatory plasma cells

Simon Fillatreau

https://ift.tt/2OHWjAm

Stillbirth Reduction Strategy Unproven

FRIDAY, Oct, 5, 2018 -- A reduced fetal movement (RFM) care package does not reduce the risk for stillbirths, according to a study published online Sept. 27 in The Lancet. Jane E. Norman, M.D., from the University of Edinburgh in the United Kingdom,...

https://ift.tt/2OKlClg

Industry-Funded Trials Often Involve Employees in Studies

FRIDAY, Oct. 5, 2018 -- Industry employees are often involved in the design, conduct, and reporting of industry-funded trials in high-impact journals, according to a study published online Oct. 3 in The BMJ. Kristine Rasmussen, from the Nordic...

https://ift.tt/2QrJMym

AZ Company Recalls Raw Beef Products Linked to Salmonella

FRIDAY, Oct. 5, 2018 -- An Arizona company has recalled more than 6.5 million pounds (2.9 million kilograms) of beef linked to a Salmonella outbreak that has sickened 57 people in 16 states. Fourteen people have been hospitalized. No deaths have...

https://ift.tt/2OEinvP

Congress Passes Bill to Fight Opioid Crisis

FRIDAY, Oct. 5, 2018 -- A bipartisan bill to fight the opioid addiction crisis in the United States has been passed by Congress. President Donald Trump said he would sign the bill into law. As part of the legislation, the U.S. Postal Service would...

https://ift.tt/2QugA9Z

Best Practices for Congenital Adrenal Hyperplasia Updated

FRIDAY, Oct. 5, 2018 -- Best practices have been updated for screening and managing congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency. The updated Endocrine Society clinical practice guideline was published online Sept....

https://ift.tt/2OEIW3Y

Toxic Metals and Trace Elements in Artisanal Honeys from the Canary Islands

Abstract

Honey is a natural product made by honey bees from the nectar of flowers or secretions produced by other living plant parts. The metal content of the honeys is related to the levels of metals in the environment. Due to the importance of honey in the human diet and the increase of environmental pollution, it is necessary to determine the content of metals in honey to evaluate the toxicological risk derived from its consumption. The objective of this study was to determine the content of 20 metals (Al, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Mo, Na, Ni, Pb, Sr, V, and Zn) in different samples of artisanal honey from the Canary Islands (Spain) in order to evaluate the dietary intake derived from the consumption of these honeys. A total of 161 samples of different types of Canary honey were analyzed by ICP-OES (inductively coupled plasma–optical emission spectrometry). K (825 mg/kg) was the macroelement found in highest concentration, while B (4.25 mg/kg) was the trace element with the highest mean concentration. Al (3.33 mg/kg) was the most abundant toxic metal, followed by Pb (0.040 mg/kg) and Cd (0.002 mg/kg). A mean consumption of 25 g/day of honey mainly contributes to the recommended daily intake of Cu (1.34% adults) and K (0.67% adults). As regards the toxic metals, the contribution percentage to the TDI (tolerable daily intake) of Pb at 2.92% for adults is noteworthy. However, the consumption of honey does not imply a high intake of metals and, therefore, does pose a risk to the health of adult men and women.

https://ift.tt/2Rv9uDh

Effect of Fe and Cd Co-Exposure on Testicular Steroid Metabolism, Morphometry, and Spermatogenesis in Mice

Abstract

The mechanism of testicular toxicity of simultaneous multiple exposures to metals is poorly understood. Previous studies reported that the toxic effect of cadmium (Cd) is modified by tissue concentration of iron (Fe). Using the mice (Mus musculus) model in the present study, we demonstrated that combined Cd (25 mg kg⁻¹ bw) and Fe (100 mg kg⁻¹ bw) treatment increased both Cd and Fe testicular concentrations much more than separate exposures to either of the metals. Intratesticular Cd and Fe concentrations were inversely correlated (r = − 0.731, p < 0.05) on administration of Fe but not on combined exposure to both metals when they were positively correlated (versus Cd; r = 0.793, versus Fe; r = 0.779, p < 0.05). Additionally, Cd + Fe treatment increased testicular lipid peroxidation and depleted intratestesticular testosterone, cholesterol and glutathione concentrations much more than their separate treatment. This was also associated with decreased activity of the germ cell marker, testicular lactate dehydrogenase, and increased testicular myeloperoxidase activity. These changes resulted in decreased seminiferous epithelial height, tubular diameter, germ cell (spermatogonia, spermatocytes, and spermatids) numbers, and severe tissue damage. In conclusion, Cd + Fe intake have synergistic toxic effects on testicular steroid formation and spermatogenesis due to the high testicular concentrations of both metals.

https://ift.tt/2yhXtIE

Early Colonoscopy for Diverticular Bleeding Does Not Reduce Risk of Post-Discharge Recurrent Bleeding—A Propensity Score Matching Analysis

Colonoscopy within 24 hours (early colonoscopy) is recommended for patients with colonic diverticular bleeding, but it is unclear if this strategy improves post-discharge outcomes. We aimed to determine whether early colonoscopy is associated with decreased risk of rebleeding and hospital readmission within 30 days.

https://ift.tt/2Cv32rT

Metabotropic glutamate receptor subtype 5 is altered in LPS-induced murine neuroinflammation model and in the brains of AD and ALS patients

Abstract

Purpose

The aim of the present study was to determine the expression levels of mGluR5 in different mouse strains after induction of neuroinflammation by lipopolysaccharide (LPS) challenge and in the brains of patients with Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) post mortem to investigate mGluR5 expression in human neurodegenerative diseases.

Methods

C57BL/6 and CD1 mice were injected intraperitoneally with either 10 mg/kg LPS or saline. mGluR5 and TSPO mRNA levels were measured after 1 and 5 days by qPCR, and mGluR5 protein levels were determined by PET imaging with the mGluR5-specific radiotracer [¹⁸F]PSS232. mGluR5 expression was evaluated in the post-mortem brain slices from AD and ALS patients using in vitro autoradiography.

Results

mGluR5 and TSPO mRNA levels were increased in brains of C57BL/6 and CD1 mice 1 day after LPS treatment and remained significantly increased after 5 days in C57BL/6 mice but not in CD1 mice. Brain PET imaging with [¹⁸F]PSS232 confirmed increased mGluR5 levels in the brains of both mouse strains 1 day after LPS treatment. After 5 days, mGluR5 levels in CD1 mice declined to the levels in vehicle-treated mice but remained high in C57BL/6 mice. Autoradiograms revealed a severalfold higher binding of [¹⁸F]PSS232 in post-mortem brain slices from AD and ALS patients compared with the binding in control brains.

Conclusion

LPS-induced neuroinflammation increased mGluR5 levels in mouse brain and is dependent on the mouse strain and time after LPS treatment. mGluR5 levels were also increased in human AD and ALS brains in vitro. PET imaging of mGluR5 levels could potentially be used to diagnose and monitor therapy outcomes in patients with AD and ALS.

https://ift.tt/2pFbso4

The European Diploma in Radiology (EDiR): investing in the future of the new generations of radiologists

Abstract

This review aims to describe the organisation and the content of the European Diploma in Radiology (EDiR). The EDiR examination is available to radiologists and radiology residents in their last year of training. It certifies that their levels of knowledge and competency are in line with the ESR European Training Curriculum for Radiology (ETC) of the European Society of Radiology (ESR). The EDiR is an additional qualification of excellence, which serves the standardisation and accreditation of radiologists across European borders. It provides an international benchmark for general radiology and is officially and fully endorsed by the European Union of Medical Specialists (UEMS) and the ESR. The EDiR is recognised as an equivalent of the Polish exit training examination, the first part of the Turkish board examination and the image interpretation part of the Finnish national examination. Moreover, in order to practice radiology in The Netherlands, trainees must either pass their national board examination or the EDiR. It has significant value in many other countries. The examination consists of three parts: Multiple Response Questions (MRQs), Short Cases (SCs) and the Clinically Oriented Reasoning Evaluation (CORE). The committees that form the EDiR Scientific Board follow a structured workflow to prepare each examination, ensuring an adequate peer review system for quality assurance.

Key Points

• EDiR helps to standardise radiology training.

• EDiR is an international certification method established across Europe.

• Ideally all training programmes should embrace EDiR as exit examination after completing their training period.

• The EDiR exam consists of multiple response questions, short cases and the Clinically Oriented Reasoning Evaluation.

https://ift.tt/2yrHF6r

Urgent start peritoneal dialysis

Purpose of review Although historically peritoneal dialysis was widely used in nephrology, it has been underutilized in recent years. In this review, we present several key opportunities and strategies for revitalization of urgent start peritoneal dialysis use, and discuss the recent literature on clinical experience with peritoneal dialysis use in the acute and unplanned setting. Recent findings Interest in using urgent start peritoneal dialysis to manage acute kidney injury (AKI) and unplanned chronic kidney disease (CKD) stage 5 patients has been increasing. To overcome some of the classic limitations of peritoneal dialysis use in AKI, such as a high chance of infectious and mechanical complications, and no control of urea, the use of cycles, flexible catheters, and a high volume of dialysis fluid has been proposed. This knowledge can be used in the case of an unplanned start on chronic peritoneal dialysis, and may be a tool to increase the peritoneal dialysis penetration rate among incident patients starting chronic dialysis therapy. Summary Peritoneal dialysis should be offered in an unbiased way to all patients starting unplanned dialysis, and without contraindications to peritoneal dialysis. It may be a feasible, well tolerated, and complementary alternative to hemodialysis, not only in the chronic setting, but also in the acute.

https://ift.tt/2NqAfps

Association between clusterin concentration and dementia: a systematic review and meta-analysis

Abstract

Studies have showed that high clusterin (CLU) concentration was associated with increased risk of dementia. However, the results based on small samples remained controversial. The aim of our study was to determine the relationship between CLU concentration and the late-life cognitive outcomes including mild cognitive impairment (MCI), Alzheimer's disease (AD), vascular dementia (VAD), Parkinson's disease related dementia (PDD), Lewy body dementia (DLB) and frontotemporal dementia (FTD). A comprehensive search was conducted to screen the eligible studies in online database PubMed, Web of Science and Embase from 1950 to January 2017 according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. The CLU concentration data in brain tissue, cerebrospinal fluid (CSF), serum and plasma was collected to determine the strength of this association. The results were presented with standard difference of the mean (SDM) with 95% confidence intervals (CIs). A total of 28 studies were identified to calculate the association between CLU concentration and dementia. The results showed that the CLU concentration in the plasma (SDM = 0.73, 95% CI 0.26–1.19, P = 0.002) and brain tissue (SDM = 0.71, 95% CI 0.10–1.32, P = 0.022) was increased in dementia compared to normal control. Subgroup analysis showed that the plasma CLU concentration was significantly increased only in the AD group (SDM = 1.85, 95% CI 0.84–2.85, P < 0.001), but not in MCI or other dementias. No association was found between serum and CSF clusterin concentration and dementia. This meta-analysis indicates that high CLU concentration in the plasma and brain is associated with dementia, especially in AD.

https://ift.tt/2QrAjH6

Editorial introductions

No abstract available

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Personalized medicine in nephrology: a novel approach or just good medicine?

No abstract available

https://ift.tt/2y2hkfQ

Hemodialysis versus peritoneal dialysis in resource-limited settings

Purpose of review To assess the use, access to and outcomes of hemodialysis and peritoneal dialysis in low-resource settings. Recent findings Hemodialysis tends to predominate because of costs and logistics, however services tend to be located in larger cities, often paid for out of pocket. Outcomes of dialysis-requiring acute kidney injury and end-stage kidney disease may be similar with hemodialysis and peritoneal dialysis, and therefore choice of therapy is dominated by availability, accessibility and patient or physician choice. Some countries have implemented peritoneal dialysis-first policies to reduce costs and improve access, because peritoneal dialysis requires less infrastructure, can be scaled up more easily and can be cheaper when fluids are manufactured locally. Summary Access to both hemodialysis and peritoneal dialysis remains highly inequitable in lower-resource settings. Although challenges associated with dialysis in low-resource settings are similar, and there are more adults who require dialysis in low-resource settings, addressing hemodialysis and peritoneal dialysis needs of children in low-resource settings requires attention as the global inequities are greatest in this area. Lower-income countries are increasingly seeking to improve access to dialysis through various strategies, but meeting the costs of the entire dialysis population continues to be a major challenge.

https://ift.tt/2NpF1Dt

How best to estimate glomerular filtration rate? Novel filtration markers and their application

Purpose of review Chronic kidney disease is an increasing health burden. Estimating equations using serum concentrations of creatinine and cystatin C facilitate the assessment of kidney function as reflected in estimated glomerular filtration rate (eGFR). Reduced eGFR is associated with increased risk for numerous adverse outcomes and is an important aspect in many clinical situations. However, current equations are suboptimal in some clinical settings. The review focuses on approaches to improve the estimation of GFR and aims to familiarize the reader with the underlying methodological hypotheses how new markers could contribute to improve the overall performance of estimating equations. Recent findings Low molecular weight proteins such as β-trace-protein and β-2-microglobulin, as well as newly discovered metabolites, show promise as new filtration markers, as they might be beneficial in populations in which creatinine or cystatin C are inaccurate. We propose that the combination of multiple novel markers, alone or in combination with creatinine, cystatin C or demographics, can potentially improve GFR estimation. For special populations such as dialysis patients, separate equations have been developed to estimate residual kidney function. Summary Current GFR estimating equations are an essential part of routine clinical practice but have limitations. The use of multiple markers combined in a single equation appears to be the most promising approach. Future research is required to validate proposed equations in diverse populations.

https://ift.tt/2y4biLx

Expanding deceased donor kidney transplantation: medical risk, infectious risk, hepatitis C virus, and HIV

Purpose of review Due to the organ shortage, which prevents over 90 000 individuals in the United States from receiving life-saving transplants, the transplant community has begun to critically reevaluate whether organ sources that were previously considered too risky provide a survival benefit to waitlist candidates. Recent findings Organs that many providers were previously unwilling to use for transplantation, including kidneys with a high Kidney Donor Profile Index or from increased risk donors who have risk factors for window period hepatitis C virus (HCV) and HIV infection, have been shown to provide a survival benefit to transplant waitlist candidates compared with remaining on dialysis. The development of direct-acting antivirals to cure HCV infection has enabled prospective trials on the transplantation of organs from HCV-infected donors into HCV-negative recipients, with promising preliminary results. Changes in legislation through the HIV Organ Policy Equity Act have legalized transplantations from HIV-positive deceased donors to HIV-positive recipients for the first time in the United States. Summary Critical reexamination of deceased donor organs that were previously discarded has resulted in greater utilization of these organs, an increased number of deceased donor transplants, and the provision of life-saving treatment to more transplant waitlist candidates.

https://ift.tt/2NlxINb

The use of bioimpedance spectroscopy to guide fluid management in patients receiving dialysis

Purpose of review To summarize the findings of recent trials and meta-analyses designed to determine whether bioimpedance spectroscopy adds value to the clinical assessment of fluid status in dialysis patients so as to achieve a normally hydrated weight and put these in a contemporary context. Recent findings Eight trials (published 2010–2018) and two meta-analyses (2017) are reviewed. Both haemodialysis and peritoneal dialysis modalities are represented. Despite considerable heterogeneity in intervention, all are open-label randomized comparisons of a bioimpedance intervention with normal clinical practice in which clinicians were blinded to bioimpedance data. In a total of 1443 patients studied, no significant differences in mortality, cardiovascular or adverse events between groups were observed. Bioimpedance use was associated with a reduction in overhydration, especially when residual kidney function was not present and a greater reduction in blood pressure. A modest correlation in the change in fluid status and fall in systolic blood pressure was seen compared to baseline. A more rapid fall in urine volume was seen in the two studies with the greatest change in fluid status, with significantly higher risk of anuria in one. How bioimpedance was integrated with the complex process of decision making by clinicians was variable and not always explained. Summary The usefulness of bioimpedance spectroscopy in guiding fluid management in dialysis patients is not yet clear. Bioimpedance can drive clinical decisions that lead to significant changes in fluid status but the best way to apply this in clinical practice requires further studies.

https://ift.tt/2y5Qwem

Techniques to improve intradialytic haemodynamic stability

Purpose of review Intra-dialytic hypotension (IDH) remains a significant problem for patients undergoing chronic haemodialysis. IDH causes symptoms that degrade patients' experience, compromises dialysis delivery and is strongly associated with adverse patient outcomes. Greater understanding of the link between IDH and dialysis-induced ischaemia in heart and brain has characterized mechanistic pathways, with repeated episodes of ischaemia resulting in organ dysfunction. This review provides updates from published evidence over the last 2 years across the range of potential interventions for IDH. Recent findings A literature search was undertaken to identify articles published in peer review journals between January 2016 and April 2018 using terms 'intradialytic hypotension,' 'haemodynamic instability,' 'ESRF,' 'renal replacement therapy,' 'dialysis' in Medline and EMBASE and identified 58 references from which 15 articles were included in this review. Interventions included: cooling the dialysate; sodium profiling; convective therapies; strategies to minimize inter-dialytic weight gain (IDWG) and improve accuracy of target weight assessment; prescribing of antihypertensive medications; and carnitine supplementation. Summary IDH remains a significant clinical problem. Recent evidence from the last 2 years does not support any major changes to current practice, with cooling of the dialysate and reduction of IDWG remaining cornerstones of management.

https://ift.tt/2y6U2oV

Update on posttransplant lymphoproliferative disease

Purpose of review Posttransplant lymphoproliferative disorder (PTLD), frequently associated with Epstein–Barr virus (EBV), is one of the most serious complications leading to worse patient and graft outcomes. Hence, we summarize in this review relevant studies published about PTLD in the last 18 months. Recent findings Recent studies have improved the knowledge about epidemiology, prophylaxis, diagnosis and PTLD treatment. Special interest has developed in improving the last PTLD classification of the World Health Organization, increasing the accuracy of diagnostic tests for EBV viral load quantification and discriminating the genetic differences between PTLD types. There seems to be no real advantage in the use of antiviral drugs for prophylaxis, but better results in therapeutic approaches are being obtained mainly with the use of rituximab with or without chemotherapy, but also with the possibility of using adoptive T-cell therapy or new drugs. Summary PTLD continues being a complication that requires continued effort of the scientific community to reduce its incidence and to develop better diagnostic tests and new strategies that improve results in prophylaxis and treatment.

https://ift.tt/2NpEZvl

Which anticoagulants should be used for stroke prevention in non-valvular atrial fibrillation and severe chronic kidney disease?

Purpose of review Non-valvular atrial fibrillation is common in patients with severe chronic kidney disease (CKD) and historically patients have been treated with vitamin K antagonists (VKA). However, these agents have questionable efficacy and are associated with increased bleeding risk. Non-vitamin K oral anticoagulants (NOAC) have advantages over VKA in early stage CKD. In this review, we sought to establish evidence for best practice in patients with severe CKD (creatinine clearance

https://ift.tt/2yaYSlh

Protein carbamylation in end stage renal disease: is there a mortality effect?

Purpose of review Protein carbamylation is a posttranslational protein modification caused, in part, by exposure to urea's dissociation product cyanate. Additional modulators of protein carbamylation include circulating free amino acid levels, inflammation, diet, smoking, and environmental pollution exposures. Carbamylation reactions can modify protein charge, structure, and function, leading to adverse molecular and cellular responses. These changes have been linked to several pathologic biochemical pathways relevant to patients with end stage renal disease (ESRD) such as accelerated atherosclerosis and dysfunctional erythropoiesis, among others. This review examines the consequences of human protein carbamylation and the clinical impact this is thought to have in patients with ESRD. Recent findings Recent well-conducted studies across diverse cohorts of patients have independently associated elevations in protein carbamylation to mortality and morbidity in patients with ESRD. Studies are now examining the best strategies to reduce carbamylation load, including interventions aimed at lowering urea levels and restoring amino acid balance. Whether such carbamylation lowering strategies yield clinical improvements remain to be determined. Summary Numerous fundamental studies provide plausible mechanisms for the observed association between protein carbamylation burden and adverse clinical outcomes in ESRD. Studies employing nutritional and dialytic interventions to lower carbamylation may mitigate this risk but the net clinical benefit has not been established.

https://ift.tt/2NqEfpD

Personalized medicine in diabetic kidney disease: a novel approach to improve trial design and patient outcomes

Purpose of review In the last decade many attempts have been made to reduce the high residual risk of end-stage kidney disease and cardiovascular disease in patients with diabetic kidney disease by targeting a variety of risk markers. Subsequent analyses revealed that the variation in individual drug response to the tested interventions partly explains why these trials did not result in additional kidney or cardiovascular protection. This review summarizes recent insights regarding individual variation in drug response. Additionally, we explore novel approaches to incorporate this drug response variability in the design of new clinical trials. Recent findings Recent studies suggest that a plausible explanation for individual therapy resistance emanates from intrinsic individual characteristics such as genetic make-up or volume status and is likely only partially explained by drug characteristics such as the dose or type of intervention. Biomarker-based enrichment strategies to identify high-risk individuals and/or those who are more likely to respond to interventions offer opportunities to tailor therapies to individual patients. Summary Individual drug response variability is a recognized phenomenon in clinical practice. It is time to implement novel approaches that take into account this response variability in the design of new trials in diabetic kidney disease in order to define optimal therapies for individual patients.

https://ift.tt/2y2h1Se

Nocturnal hemodialysis: an underutilized modality?

Purpose of review There is increasing evidence that extended-hours regimens are associated with improved outcomes for patients on maintenance hemodialysis programs. Home hemodialysis programs are a well established way for patients to benefit from extended-hours dialysis overnight; however, there are significant barriers to home hemodialysis, which means that for many this is not an option. In center, nocturnal hemodialysis is an increasingly recognized way of offering extended-hours treatment to patients unable to undertake home-based programs and is an underutilized modality for such patients to gain from the physiological benefits of extended-hours dialysis regimens. Recent findings Recent data suggest that nocturnal dialysis programs confer a significant survival advantage over both standard dialysis and short-daily dialysis regimens with evidence proposing that this is mediated through beneficial cardiovascular remodeling. Moreover, there is strong evidence that nocturnal dialysis regimens associate with significant improvements in quality-of-life measures and social well being. Summary Nocturnal hemodialysis is an underutilized way of offering extended-hours hemodialysis to patients in both the home and in-center environments. As the evidence base around nocturnal dialysis grows, clinicians and dialysis providers are becoming increasingly obliged to investigate implementation strategies for nocturnal dialysis services to improve patient outcomes and experience of care.

https://ift.tt/2NnxogU

Systems biology approaches to identify disease mechanisms and facilitate targeted therapy in the management of glomerular disease

Purpose of review Current clinical pathological classifications of glomerular diseases are inadequate at predicting patient disease progression or response to therapy. With the advent of precision medicine and its successes in oncology, it is important to understand if similar approaches in glomerular diseases can improve patient management. The purpose of this review is to summarize approaches to obtain comprehensive molecular profiles from human biopsies and utilize them to define the pathophysiology of glomerular failure. Recent findings Multicenter research networks have provided the framework to capture both prospective clinical disease course and patterns of end organ damage in biopsy cohorts. With these sample and data sets in hand, efforts are progressing towards molecular disease characterization, identification of novel prognostic marker, development of more precise clinical trials and discovery of predictive biomarkers to more effectively stratify patients to appropriate treatment regiments. Partnerships between academia, public funding agencies and private companies seek to improve timelines and maximize resources while also leveraging domain expertise in an integrated framework to holistically understand disease. Summary The application of system biology techniques within team science frameworks across disciplines and continents will seek to realize the impact of precision medicine to bring urgently needed novel therapeutic options to patients with glomerular disease.

https://ift.tt/2y28Chg

Point-of-care ultrasound in end-stage kidney disease: beyond lung ultrasound

Purpose of review Following the miniaturization of ultrasound devices, point-of-care ultrasound (POCUS) has been proposed as a tool to enhance the value of physical examination in various clinical settings. The objective of this review is to describe the potential applications of POCUS in end-stage renal disease patients (ESRD). Recent findings With basic training, the clinician can perform pulmonary, vascular, cardiac, and abdominal POCUS at the bedside of ESRD patients. Pulmonary ultrasound can be used to quantify pulmonary congestion and for the differential diagnosis of dyspnea. Ultrasound of the inferior vena cava combined with simple cardiac ultrasound can be used to promptly investigate the mechanism of hemodynamic instability. Vascular ultrasound can be used for troubleshooting of arteriovenous fistula problems and for catheter installation. Multiple potential applications of POCUS in the ESRD population are reviewed, including areas of future research. Summary Acquiring basic skills in POCUS may improve patient care through the rapid identification of threats, improved diagnostic abilities for common symptoms, and safer procedures. The adoption of POCUS in undergraduate, internal medicine and nephrology training curriculums will likely lead to a gradual introduction of this technology in the care of ESRD patients.

https://ift.tt/2NpF0zp

Eating As Treatment (EAT): a stepped-wedge, randomised controlled trial of a health behaviour change intervention provided by dietitians to improve nutrition in patients with head and neck cancer undergoing radiotherapy (TROG 12.03)

Malnutrition during head and neck cancer is associated with poorer morbidity and mortality outcomes. This trial assessed the effectiveness of a psychological intervention delivered by dietitians to prevent malnutrition in head and neck cancer patients while having radiotherapy. Those patients that received the intervention had significantly better nutritional scores; lost less weight; had fewer radiotherapy interruptions; had lower depression scores; and reported a higher quality of life.

https://ift.tt/2RuXeTu

Patterns of care and outcome Radiation-Induced Soft Tissue Sarcomas

More than half of all cancer patients receive radiotherapy. With the increasing number of long-term cancer survivors, there is a growing concern about the risk of radiation induced second malignant neoplasm. Sarcomas represent the most frequent type of cancer than can be induced by radiation exposure. We report the largest series of radiation-induced sarcomas (RIS). We demonstrate that a majority of RIS can be cured, provided they underwent well-planned surgery.

https://ift.tt/2yhIqyE

Airway Microbiome and Development of Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review

To summarize evidence regarding microbial dysbiosis of the airway associated with bronchopulmonary dysplasia (BPD) and to explore heterogeneity among studies.

https://ift.tt/2E36Qly

Urine Acidification After Ammonium Chloride

Urine acidification is the net effect of HCO3– reabsorption, H+ secretion, and the presence of buffers. A defect in H+ secretion in the collecting duct causes distal renal tubular acidosis (dRTA). In patients with minimal reductions in HCO3–, urine acidification tests such as the NH4Cl test and the furosemide fludrocortisone (FF) test are used to reveal incomplete forms of dRTA.1-3 Patients with dRTA do not adequately lower their urine pH in response to these acidification tests. However, recent reports showed discrepant results between the NH4Cl and FF tests in a substantial number of patients with suspected dRTA.

https://ift.tt/2Qziczn

The Role of Vitamin D in CKD Stages 3 to 4: Report of a Scientific Workshop Sponsored by the National Kidney Foundation

Deficiency of 25-hydroxyvitamin D (25[OH]D) is common in patients with chronic kidney disease stages 3 and 4 and is associated with poor outcomes. However, the evaluation and management of vitamin D deficiency in nephrology remains controversial. This article reports on the proceedings from a "controversies conference" on vitamin D in chronic kidney disease that was sponsored by the National Kidney Foundation. The report outlines the deliberations of the 3 work groups that participated in the conference.

https://ift.tt/2OH7mK9

The Prevalence of Rib Fractures Incidentally Identified by Chest Radiograph among Infants and Toddlers

To determine the prevalence of incidental rib fractures identified by chest radiograph (CXR) obtained for indications unrelated to accidental trauma or nonaccidental trauma (NAT), and describe the histories associated with cases of incidental rib fractures and their proposed etiologies. It is hypothesized that incidental rib fractures are rare and alternative explanations for rib fractures occasionally used in a medico-legal context such as minor accidental trauma, undiagnosed medical conditions, and transient metabolic bone disturbances are unlikely to be the etiology of incidental rib fractures.

https://ift.tt/2E36V8Q

Occipital Dermal Sinus: The Tip of the Iceberg

A 2-year-old girl presented with a congenital occipital lump centered by a tuft of coarse hair with a small orifice (Figure, A); this had grown and developed a purulent flow over 1 year. She had no neurologic symptoms and no history of fever. Her general practitioner prescribed topical antiseptic and antibiotic, but the lump recurred. An ultrasound scan revealed a subcutaneous fistulous tract communicating with a deeper mass lysing the occipital bone. Computed tomography and magnetic resonance imaging scans documented a dermal sinus connected to an intradiploic occipital dermoid cyst (Figure, B-E).The full lesion was resected through a suboccipital approach.

https://ift.tt/2O7cQOM

Effects of Prone Sleeping on Cerebral Oxygenation in Preterm Infants

To determine the effect of prone sleeping on cerebral oxygenation in preterm infants in the neonatal intensive care unit.

https://ift.tt/2O7cN5y

Screening for Toxic Stress Risk Factors at Well-Child Visits: The Addressing Social Key Questions for Health Study

To determine the prevalence of and demographic characteristics associated with toxic stress risk factors by universal screening, the impact of screening on referral rates to community resources, and the feasibility and acceptability of screening in a medical home setting.

https://ift.tt/2E9ZYmK

Factors Associated with Adverse Outcomes among Febrile Young Infants with Invasive Bacterial Infections

To determine factors associated with adverse outcomes among febrile young infants with invasive bacterial infections (IBIs) (ie, bacteremia and/or bacterial meningitis).

https://ift.tt/2O9QV9X

Birth Hospitalization Costs and Days of Care for Mothers and Neonates in California, 2009-2011

To provide population-based estimates of the hospital-related costs of maternal and newborn care, and how these vary by gestational age and birth weight.

https://ift.tt/2OdoTdK

Assessment of Body Mass Index in Infancy: It Is Time to Revise Our Guidelines

Infancy, a time of substantial growth, is also a critical period for the development of obesity risk. Many studies have identified that rapid or excessive weight gain during infancy is associated with increased risk for childhood obesity,1 as well as later-life obesity and cardiometabolic dysregulation.2,3 Weight gain during infancy does not fully capture growth during this time, however, because the amount and pace of growth in length also have implications for infants' body proportionality, body composition,4 and obesity risk5 in early childhood.

https://ift.tt/2E36YS4

Predominance of Rotavirus G8P[8] in a City in Chile, a Country Without Rotavirus Vaccination

Rotavirus G8P[8] infection has been common in Africa, but rare in the Americas. Among 23 rotavirus episodes observed during 18 months of surveillance of 100 families in Chile, 11 (48%) were identified as G8P[8]. Genotypes from these strains shared >99% identity with rotavirus sequences described in Asia, and may be misclassified as mixed G8/G12.

https://ift.tt/2E36T0I

Predicting Maintenance of Any Breastfeeding from Exclusive Breastfeeding Duration: A Replication Study

To predict the duration of any breastfeeding using the duration of exclusive breastfeeding in a socioeconomically heterogeneous sample of mothers using receiver operator characteristic (ROC) analysis.

https://ift.tt/2O7cJmk

A review on microelectrode recording selection of features for machine learning in deep brain stimulation surgery for Parkinson’s disease

Parkinson's disease (PD) is a progressive, neurodegenerative disease characterized by motor symptoms that include bradykinesia, resting tremor, postural instability, and rigidity leading to significant effects on patient's quality of life. (Brocker et al., 2017; Gulberti et al., 2015). High frequency deep brain stimulation (DBS), to either the globus pallidus internus (GPi) or subthalamic nucleus (STN) (Williams et al., 2014), is an effective surgical treatment for moderate to advanced PD that improves motor symptoms and quality of life (Brocker et al., 2017; Holt and Netoff, 2016; Karamintziou et al., 2016, 2017; Kühn and Volkmann, 2017; Rowland et al., 2017).

https://ift.tt/2zUYokj

Induction and Evaluation of Inbreeding Crosses Using the Ant, Vollenhovia Emeryi

In this protocol, methods for conducting inbreeding crosses, and for evaluating the success of those crosses, are described for the ant Vollenhovia emeryi. These protocols are important for experiments aimed at understanding the genetic basis of sex determination systems in Hymenoptera.

https://ift.tt/2pExkQy

A View of Their Own: Capturing the Egocentric View of Infants and Toddlers with Head-Mounted Cameras

Infants and toddlers view the world in a fundamentally different way from their parents. Head-mounted cameras provide a tractable mechanism to understand the infant visual environment. This protocol provides guiding principles for experiments in the home or laboratory to capture the egocentric view of toddlers and infants.

https://ift.tt/2IEccSU

Visual Classical Conditioning in Wood Ants

We present a protocol for the classical conditioning of harnessed ants that permits researchers to study visual learning and memory formation at a level of analysis not possible with freely moving individuals.

https://ift.tt/2pALvG9

FDG PET/CT for assessing tumour response to immunotherapy

Abstract

This paper follows the immunotherapy symposium held during the European Association of Nuclear Medicine (EANM) 2017 Annual Congress. The biological basis of the immune checkpoint inhibitors and the drugs most frequently used for the treatment of solid tumours are reviewed. The issues of pseudoprogression (frequency, timeline), hyperprogression and immune-related side effects are discussed, as well as their implications for patient management. A review of the recent literature on the use of FDG PET for assessment of immunotherapy is presented, and recommendations are provided for assessing tumour response and reporting immune-related side effects with FDG PET based on published data and experts' experience. Representative clinical cases are also discussed.

https://ift.tt/2OaHvuw

Practicing on the deceased: ‘I get it’

The human body is an ideal training tool, but fire/EMS training protocols and the law must be followed

https://ift.tt/2PdIzdH

A Model of Glaucoma Induced by Circumlimbal Suture in Rats and Mice

Chronic ocular hypertension is induced by applying a circumlimbal suture in rats and mice, leading to functional and structural deterioration of the retinal ganglion cells consistent with glaucoma.

https://ift.tt/2zUWMqK

Controllable Nucleation of Cavitation from Plasmonic Gold Nanoparticles for Enhancing High Intensity Focused Ultrasound Applications

This protocol demonstrates the controllable nucleation of cavitation in gel phantoms, through simultaneous exposure to both near-infrared pulsed laser light and high intensity focused ultrasound (HIFU). The cavitation activity can then be used for enhancing imaging and/or therapeutic uses of HIFU.

https://ift.tt/2Pbt9a0

More Than 14 Million Preteens Need to Receive HPV Vaccine

FRIDAY, Oct. 5, 2018 -- More than 14 million additional 11- to 12-year-olds need to be vaccinated to reach the American Cancer Society goal of 80 percent of adolescents being up to date (UTD) with the human papillomavirus vaccination (HPVV) by their...

https://ift.tt/2yip24N

Lixisenatide Cuts Kidney Damage in T2DM and Coronary Syndrome

FRIDAY, Oct. 5, 2018 -- For patients with type 2 diabetes and acute coronary syndrome, lixisenatide can slow or prevent damage to the kidneys, according to a study published online Oct. 3 in The Lancet Diabetes & Endocrinology. The research was...

https://ift.tt/2O9DW7V

Daily Drinking Associated With Increased Mortality Risk

FRIDAY, Oct. 5, 2018 -- Daily drinking, even at low levels, may be detrimental to one's health, according to a study published online Oct. 3 in Alcoholism: Clinical & Experimental Research. Sarah M. Hartz, M.D., Ph.D., from Washington University...

https://ift.tt/2yloBGW

Digital Cognitive Therapy Eases Daytime Effects of Insomnia

FRIDAY, Oct. 5, 2018 -- Digital cognitive behavioral therapy (dCBT) is effective in improving functional health, psychological well-being, and sleep-related quality of life in people reporting insomnia, according to a study published online Sept. 25...

https://ift.tt/2O9DWVt

Clinical Comorbidities Up After Arthroscopic Hip Surgery

FRIDAY, Oct. 5, 2018 -- Following elective arthroscopic hip surgery, the rate of seven major clinical comorbidities increases significantly, according to a study published online Sept. 27 in the British Journal of Sports Medicine. Daniel I. Rhon,...

https://ift.tt/2ylozyO

No Increase in In-Hospital, Post-Discharge Death With HRRP

FRIDAY, Oct. 5, 2018 -- Announcement and implementation of the Hospital Readmissions Reduction Program (HRRP) was not associated with increases in in-hospital or post-discharge mortality after acute myocardial infarction (AMI), heart failure, or...

https://ift.tt/2OcyaTn

Sexual Harassment, Assault Tied to Women's Health Issues

FRIDAY, Oct. 5, 2018 -- Sexual harassment and sexual assault among midlife women are associated with poorer physical and mental health, according to a study published online Oct. 3 in JAMA Internal Medicine. Rebecca C. Thurston, Ph.D., from the...

https://ift.tt/2Obpwo0

One-Third of Older Adults Die After Emergency Intubation

FRIDAY, Oct. 5, 2018 -- Of older adults who undergo intubation in the emergency department, 33 percent die during the index hospitalization, according to a study published recently in the Journal of the American Geriatrics Society. Kei Ouchi, M.D.,...

https://ift.tt/2yiglr4

Models Predict Intracerebral Hemorrhage Growth

FRIDAY, Oct. 5, 2018 -- Models using four or five predictors have acceptable to good discrimination for determining additional intracerebral hemorrhage growth in patients with acute intracerebral hemorrhage, according to a review published in the...

https://ift.tt/2OcyDoj

Morbidity, Mortality Up for Youth With CHD Presenting to ED

FRIDAY, Oct. 5, 2018 -- Children with congenital heart disease (CHD) presenting to the emergency department have increased rates of inpatient admission and mortality and higher emergency department charges than those without CHD, according to a...

https://ift.tt/2yhqIeC

Which is the proper reference tissue for measuring the change in FDG PET metabolic volume of cardiac sarcoidosis before and after steroid therapy?

Abstract

Background

Cardiac sarcoidosis (CS) is a rare but potentially life-threatening disease that causes conduction disturbance, systolic dysfunction, and, most notably, sudden cardiac death. ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) plays important roles not only in diagnosing CS but also in evaluating the effects of anti-inflammatory therapy. A volume-based analysis of parameters measured by FDG PET, so-called cardiac metabolic volume (CMV), has emerged as a new assessment tool. CMV is measured as the volume within the boundary determined by a reference tissue such as the liver and the blood pool uptake. However, there is a possibility that oral steroid therapy could lead to variations of the liver and the blood pool uptake. Here, we attempted to evaluate the steroid effects on the liver and the blood pool uptake.

A total of 38 CS patients who underwent FDG PET/CT before and during steroid therapy were retrospectively enrolled. Volumes of interest (VOIs) were placed in the right lobe of the liver and descending aorta (DA). The maximum standardized uptake value (SUVmax), SUVmean, and SUVpeak of the liver and DA were compared between time points before and during steroid therapy.

Results

The SUVmax, SUVmean, and SUVpeak of the liver during steroid therapy significantly increased from the time point before the therapy (SUVmax 3.5 ± 0.4 vs. 3.8 ± 0.6, p = 0.014; SUVmean 2.7 ± 0.3 vs. 3.0 ± 0.5, p = 0.0065; SUVpeak 3.0 ± 0.4 vs. 3.4 ± 0.6, p = 0.006). However, the SUVmax, SUVmean, and SUVpeak in the DA did not significantly change (SUVmax 2.2 ± 0.3 vs. 2.2 ± 0.4, p = 0.46; SUVmean 1.9 ± 0.3 vs. 2.0 ± 0.4, p = 0.56; SUVpeak 2.0 ± 0.3 vs. 2.0 ± 0.3, p = 0.70).

Conclusions

We measured FDG uptake in the liver and blood pool before and during steroid therapy. Steroid therapy increased the liver uptake but not the blood pool uptake. Our findings suggested that the DA uptake is a more suitable threshold than liver uptake to evaluate therapeutic effects using volume-based analysis of cardiac FDG PET.

https://ift.tt/2RuX4eT

High-throughput Identification of Gene Regulatory Sequences Using Next-generation Sequencing of Circular Chromosome Conformation Capture (4C-seq)

The identification of physical interactions between genes and regulatory elements is challenging but has been facilitated by chromosome conformation capture methods. This modification to the 4C-seq protocol mitigates PCR bias by minimizing over-amplification of PCR templates and maximizes the mappability of reads by incorporating an addition restriction enzyme digest step.

https://ift.tt/2Nq2lkl

Uncoupling Coriolis Force and Rotating Buoyancy Effects on Full-Field Heat Transfer Properties of a Rotating Channel

Here, we present an experimental method for decoupling the interdependent Coriolis-force and rotating-buoyancy effects on full-field heat transfer distributions of a rotating channel.

https://ift.tt/2OCYOnx

How a multiple-patient transport vehicle can help you prepare for any disaster

Responding to individual emergencies comes naturally for EMS personnel, but what about mass casualty incidents?

https://ift.tt/2E211F3

Cancers, Vol. 10, Pages 372: Audencel Immunotherapy Based on Dendritic Cells Has No Effect on Overall and Progression-Free Survival in Newly Diagnosed Glioblastoma: A Phase II Randomized Trial

Cancers, Vol. 10, Pages 372: Audencel Immunotherapy Based on Dendritic Cells Has No Effect on Overall and Progression-Free Survival in Newly Diagnosed Glioblastoma: A Phase II Randomized Trial

Cancers doi: 10.3390/cancers10100372

Authors: Johanna Buchroithner Friedrich Erhart Josef Pichler Georg Widhalm Matthias Preusser Günther Stockhammer Martha Nowosielski Sarah Iglseder Christian F. Freyschlag Stefan Oberndorfer Karin Bordihn Gord von Campe Markus Hoffermann Reinhard Ruckser Karl Rössler Sabine Spiegl-Kreinecker Michael B. Fischer Thomas Czech Carmen Visus Günther Krumpl Thomas Felzmann Christine Marosi

Dendritic cells (DCs) are antigen-presenting cells that are capable of priming anti-tumor immune responses, thus serving as attractive tools to generate tumor vaccines. In this multicentric randomized open-label phase II study, we investigated the efficacy of vaccination with tumor lysate-charged autologous DCs (Audencel) in newly diagnosed glioblastoma multiforme (GBM). Patients aged 18 to 70 years with histologically proven primary GBM and resection of at least 70% were randomized 1:1 to standard of care (SOC) or SOC plus vaccination (weekly intranodal application in weeks seven to 10, followed by monthly intervals). The primary endpoint was progression-free survival at 12 months. Secondary endpoints were overall survival, safety, and toxicity. Seventy-six adult patients were analyzed in this study. Vaccinations were given for seven (3&ndash;20) months on average. No severe toxicity was attributable to vaccination. Seven patients showed flu-like symptoms, and six patients developed local skin reactions. Progression-free survival at 12 months did not differ significantly between the control and vaccine groups (28.4% versus 24.5%, p = 0.9975). Median overall survival was similar with 18.3 months (vaccine: 564 days, 95% CI: 436&ndash;671 versus control: 568 days, 95% CI: 349&ndash;680; p = 0.89, harzard ratio (HR) 0.99). Hence, in this trial, the clinical outcomes of patients with primary GBM could not be improved by the addition of Audencel to SOC.

https://ift.tt/2pFJ98N

Implication of non-coding PAX6 mutations in aniridia

Abstract

There is an increasing implication of non-coding regions in pathological processes of genetic origin. This is partly due to the emergence of sophisticated techniques that have transformed research into gene expression by allowing a more global understanding of the genome, both at the genomic, epigenomic and chromatin levels. Here, we implemented the analysis of PAX6, whose coding loss-of-function variants are mainly implied in aniridia, by studying its non-coding regions (untranslated regions, introns and cis-regulatory sequences). In particular, we have taken advantage of the development of high-throughput approaches to screen the upstream and downstream regulatory regions of PAX6 in 47 aniridia patients without identified mutation in the coding sequence. This was made possible through the use of custom targeted resequencing and/or CGH array to analyze the entire PAX6 locus on 11p13. We found candidate variants in 30 of the 47 patients. 9/30 correspond to the well-known described 3′ deletions encompassing SIMO and other enhancer elements. In addition, we identified numerous different variants in various non-coding regions, in particular untranslated regions. Among these latter, most of them demonstrated an in vitro functional effect using a minigene strategy, and 12/21 are thus considered as causative mutations or very likely to explain the phenotypes. This new analysis strategy brings molecular diagnosis to more than 90% of our aniridia patients. This study revealed an outstanding mutation pattern in non-coding PAX6 regions confirming that PAX6 remains the major gene for aniridia.

https://ift.tt/2BYsO6z

Soil amendment with sewage sludge affects soil prokaryotic community composition, mobilome and resistome

Abstract

Municipal sewage sludge (MSS) is often directly applied to fields despite concerns regarding the spread of harmful microbes and associated resistance genes (RGs). In this four month microcosm study, the dynamics of prokaryotic communities in agricultural soil and changes in mobile genetic elements (MGEs) and RGs following amendment with stabilized MSS was investigated. TaqMan-based quantitative real-time (q)PCR showed that RG prevalence was high when compared to untreated soil and genes for class 1 integrons (intI1), streptomycin RGs (aadA, strA) and tetracycline RG (tet(W)), were detectable for the duration of the four month study. High-throughput qPCR revealed an enhanced prevalence of aminoglycoside RGs (aacC, aadE), macrolide lincosamide-streptogramin B RGs (ermB, ermF) and tetracycline RGs (tet(L), tet(M), tet(X)). Illumina MiSeq sequencing of 16S rRNA gene fragments amplified from total community DNA revealed significant changes in the prokaryotic community composition both at phylum and genus levels, with lower richness and evenness after MSS amendment followed by gradual recovery after 119 days. Conjugative plasmids captured from MSS using exogenous isolation belonged predominantly to the IncP-1 plasmid group. Our results provide new insights into short- and medium-term effects of MSS amendment on soil prokaryotic communities, including the mobilome and resistome.

https://ift.tt/2yhb2bi

Expression dynamics of the poly-γ-glutamic acid biosynthesis genes of Bacillus subtilis in response to glucose and glutamic acid-A pilot study

Abstract

Poly-γ-glutamic acid (PGA) is biosynthesized by various Bacillus species through PGA synthetase, encoded by PGA operon comprising of ywsC and ywtABC genes. Due to the minimal available knowledge, understanding the expression pattern of PGA operon genes is pivotal. In this study, the effect of glucose and glutamic acid on global gene expression profile of Bacillus subtilis Natto3 was investigated using high throughput microarray, with an emphasis on PGA operon and genes influencing PGA production. Two treatment groups (set1-in presence of glutamic acid and set2-in presence of glutamic acid+glucose) were analyzed against control, (in presence of glucose). In Microarray, both the groups, showed trend of up-regulation for ywsC and ywtA genes (log2 fold change of 0.55, p=0.0194, 0.92, p=0.0069 in set1 and 0.78, p=0.0023, 0.59, p=0.0172 in set2, respectively) and down-regulation of ywtB and ywtC genes (log2 fold change of -1.83, p=0.0001, -1.42, p=0.0017 in set1 and -1.52, p=0.0012, -0.55, p=0.1112 in set2, respectively), supporting indispensability of ywsC and ywtA genes in PGA production. Interestingly, ywtB and ywtC genes, belonging to the same operon were down-regulated in both the conditions (set1 and set2). To the best of our knowledge, this expression pattern of PGA operon genes is a unique observation.

https://ift.tt/2y2OpIc

Computational Functionalism for the Deep Learning Era

Abstract

Deep learning is a kind of machine learning which happens in a certain type of artificial neural networks called deep networks. Artificial deep networks, which exhibit many similarities with biological ones, have consistently shown human-like performance in many intelligent tasks. This poses the question whether this performance is caused by such similarities. After reviewing the structure and learning processes of artificial and biological neural networks, we outline two important reasons for the success of deep learning, namely the extraction of successively higher level features and the multiple layer structure, which are closely related to each other. Then some indications about the framing of this heated debate are given. After that, an assessment of the value of artificial deep networks as models of the human brain is given from the similarity perspective of model representation. Finally, a new version of computational functionalism is proposed which addresses the specificity of deep neural computation better than classic, program based computational functionalism.

https://ift.tt/2Plsh2k

Cancers, Vol. 10, Pages 371: Unliganded Progesterone Receptor Governs Estrogen Receptor Gene Expression by Regulating DNA Methylation in Breast Cancer Cells

Cancers, Vol. 10, Pages 371: Unliganded Progesterone Receptor Governs Estrogen Receptor Gene Expression by Regulating DNA Methylation in Breast Cancer Cells

Cancers doi: 10.3390/cancers10100371

Authors: Gaetano Verde Lara I. De Llobet Roni H.G. Wright Javier Quilez Sandra Peiró François Le Dily Miguel Beato

Breast cancer prognosis and response to endocrine therapy strongly depends on the expression of the estrogen and progesterone receptors (ER and PR, respectively). Although much is known about ER&alpha; gene (ESR1) regulation after hormonal stimulation, how it is regulated in hormone-free condition is not fully understood. We used ER-/PR-positive breast cancer cells to investigate the role of PR in ESR1 regulation in the absence of hormones. We show that PR binds to the low-methylated ESR1 promoter and maintains both gene expression and DNA methylation of the ESR1 locus in hormone-deprived breast cancer cells. Depletion of PR reduces ESR1 expression, with a concomitant increase in gene promoter methylation. The high amount of methylation in the ESR1 promoter of PR-depleted cells persists after the stable re-expression of PR and inhibits PR binding to this genomic region. As a consequence, the rescue of PR expression in PR-depleted cells is insufficient to restore ESR1 expression. Consistently, DNA methylation impedes PR binding to consensus progesterone responsive elements. These findings contribute to understanding the complex crosstalk between PR and ER and suggest that the analysis of ESR1 promoter methylation in breast cancer cells can help to design more appropriate targeted therapies for breast cancer patients.

https://ift.tt/2O6wL0y

Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules

Abstract

Background

Microenvironment cues involved in melanoma progression are largely unknown. Melanoma is highly influenced in its aggressive phenotype by the changes it determinates in its microenvironment, such as pH decrease, in turn influencing cancer cell invasiveness, progression and tissue remodelling through an abundant secretion of exosomes, dictating cancer strategy to the whole host. A role of exosomes in driving melanoma progression under microenvironmental acidity was never described.

Methods

We studied four differently staged human melanoma lines, reflecting melanoma progression, under microenvironmental acidic pHs pressure ranging between pH 6.0–6.7. To estimate exosome secretion as a function of tumor stage and environmental pH, we applied a technique to generate native fluorescent exosomes characterized by vesicles integrity, size, density, markers expression, and quantifiable by direct FACS analysis.

Functional roles of exosomes were tested in migration and invasion tests. Then we performed a comparative proteomic analysis of acid versus control exosomes to elucidate a specific signature involved in melanoma progression.

Results

We found that metastatic melanoma secretes a higher exosome amount than primary melanoma, and that acidic pH increases exosome secretion when melanoma is in an intermediate stage, i.e. metastatic non-invasive.

We were thus able to show that acidic pH influences the intercellular cross-talk mediated by exosomes. In fact when exposed to exosomes produced in an acidic medium, pH naïve melanoma cells acquire migratory and invasive capacities likely due to transfer of metastatic exosomal proteins, favoring cell motility and angiogenesis.

A Prognoscan-based meta-analysis study of proteins enriched in acidic exosomes, identified 11 genes (HRAS, GANAB, CFL2, HSP90B1, HSP90AB1, GSN, HSPA1L, NRAS, HSPA5, TIMP3, HYOU1), significantly correlating with poor prognosis, whose high expression was in part confirmed in bioptic samples of lymph node metastases.

Conclusions

A crucial step of melanoma progression does occur at melanoma intermediate –stage, when extracellular acidic pH induces an abundant release and intra-tumoral uptake of exosomes. Such exosomes are endowed with pro-invasive molecules of clinical relevance, which may provide a signature of melanoma advancement.

https://ift.tt/2OGuXus

5 ways to eliminate dosing errors

Remain consistent once you've established the patient's weight, ensure you know what's in your containers and practice dosing calculations to prevent errors

https://ift.tt/2xUIKEf

Vaping Pods Produce High Nicotine Levels in Young Users

Adolescents who use pod-style e-cigarettes had higher levels of nicotine in their bodies than is typically found in adolescents who smoke conventional cigarettes, a new study has found. The study's findings are concerning for several reasons.

https://ift.tt/2NonSdp

Impact of the epidermal growth factor receptor mutation status on the prognosis of recurrent adenocarcinoma of the lung after curative surgery

Abstract

Background

The prognosis of patients with epidermal growth factor receptor (EGFR) mutant adenocarcinoma of the lung (Mt) and EGFR wild-type adenocarcinoma (Wt) after complete resection of the lung differ; however, the mechanisms responsible for these differences remain unclear. The present study examined the post-operative prognosis of recurrent pulmonary adenocarcinoma patients to evaluate the clinicopathological nature of Mt and contribution of EGFR - tyrosine kinase inhibitors (TKI) to the prognosis of patients.

Methods

The subjects were 237 patients with recurrent pulmonary adenocarcinoma who underwent EGFR mutation analysis, and consisted of 108 patients with recurrent Mt and 129 with recurrent Wt. Multivariate analyses were performed to investigate whether the EGFR status is a prognostic factor for relapse-free survival (RFS) and post-relapse survival (PRS).

Results

RFS was significantly better in Mt than in Wt patients; median RFS were 20.2 and 13.3 months, respectively (p < 0.001). The multivariate analysis identified EGFR mutation as an independent prognostic factor for a favorable RFS (hazard ratio = 0.68; 95% confidence interval, 0.52–0.89). Although, no significant differences were observed in PRS between Mt and Wt patients (median PRS were 33.9 and 28.2 months, respectively; p = 0.360), PRS was significantly better in Mt with EGFR - TKI than in Wt and Mt patients without EGFR - TKI (p = 0.008 and p < 0.001, respectively). PRS was also significantly better in Wt than in Mt patients without EGFR - TKI (p < 0.001). The multivariate analysis identified the administration of EGFR - TKI as an independent prognostic factor for PRS (hazard ratio = 0.60; 95% confidence interval, 0.40–0.89).

Conclusions

EGFR mutation tumors were associated with a significantly better RFS for recurrent pulmonary adenocarcinoma after curative resection of the lung, which represented the less aggressive nature of Mt tumors. However, patients with Mt did not have a favorable prognosis after recurrence unless they received EGFR - TKI.

https://ift.tt/2E1DuUE

Oral mucositis associated with anti-EGFR therapy in colorectal cancer: single institutional retrospective cohort study

Abstract

Background

Chemotherapy-induced oral mucositis impairs the quality of life. The difference in severity of oral mucositis between different anti-epidermal growth factor receptor (EGFR) antibodies combined with cytotoxic drugs in colorectal cancer is unclear. The aim of this study was to investigate the differences in oral mucositis between panitumumab (Pmab) and cetuximab (Cmab) combined with 5-fluorouracil (5-FU).

Methods

We conducted a retrospective cohort study. A total of 75 colorectal cancer outpatients treated with an anti-EGFR antibody combined with FOLFOX, FOLFIRI, or 5-FU/leucovorin as the first- to third-line treatment were included. The primary endpoint was the incidence of grade 2–3 oral mucositis. The secondary endpoint was the time to onset of oral mucositis. We also compared the incidence of toxicities of interest, skin toxicity, hypomagnesaemia and neutropenia, and time to treatment failure (TTF) between the two groups.

Results

Thirty-two patients treated with Pmab and 43 patients treated with Cmab were evaluated. Patient characteristics were similar between the two groups. The incidence of grade 2–3 oral mucositis was significantly higher with Pmab than with Cmab (31.3% vs 9.3%, P < 0.05). Moreover, the incidence of grade 3 oral mucositis was significantly higher in patients treated with Pmab (18.8% vs 0%, P < 0.01). The mean (SD) cycles to onset of the worst oral mucositis was 3.0 (2.9) in the Pmab group and 2.3 (1.7) in the Cmab group (P = 0.29). Oral mucositis was characterized by glossitis and cheilitis. The incidences of other toxicities were the following (Pmab vs Cmab): grade 2–3 skin toxicity: 68.8% vs 74.4% (P = 0.61), grade 2–3 hypomagnesaemia: 9.3% vs 7.0% (P = 1.00), grade 3–4 neutropenia: 28.1% vs 37.2% (P = 0.46). The median TTF was not significantly different, i.e., 223 days vs 200 days (P = 0.39) for Pmab vs Cmab.

Conclusions

Pmab-based chemotherapy resulted in significantly higher grades of oral mucositis compared with Cmab-based chemotherapy. The oral condition should be monitored carefully and early supportive care should be provided for patients treated with Pmab-based chemotherapy.

https://ift.tt/2O7pr4t

Risk factors for paclitaxel-induced peripheral neuropathy in patients with breast cancer

Abstract

Background

Paclitaxel induced peripheral neuropathy (PIPN) is a major debilitating side effect of paclitaxel in patients with breast cancer with no fully known mechanisms. The aim of the study was to find out the possible risk factors for PIPN.

Methods

Eligible patients with node positive breast cancer undergoing chemotherapy with paclitaxel were assessed. They belonged to an initial randomized controlled trial in which the effectiveness of omega-3 fatty acids in preventing and reducing severity of PIPN was evaluated (protocol ID: NCT01049295). Reduced total neuropathy score (r-TNS) was used for measuring PIPN. All analyses were performed adjusting for intervention effect. The association between age, BMI, BSA, pathological grade, molecular biomarkers and PIPN was evaluated.

Results

Fifty-seven patients with breast cancer were investigated. Age was significantly associated with risk of PIPN (RR:1.50, P value = .024). Body mass index and BSA had significant association with severity of PIPN (B:1.28, P = .025; and B: 3.88, P = .010 respectively). Also, BSA showed a significant association with the risk of PIPN (RR: 2.28, P = .035; B: 3.88, P = .035). Incidence and severity of PIPN were much more pronounced in progesterone receptor positive (PR⁺) patients (RR:1.88, P = .015 and B:1.54, P = .012). Multivariate analysis showed that age and the status of PR⁺ were independent risk factor for incidence and the status of PR⁺ was the only independent risk factor for severity of PIPN.

Conclusion

Age, BSA and the status of PR⁺, should be considered as the risk factors for PIPN before commencement of chemotherapy with paclitaxel in patients with breast cancer. Older patients, those with greater BSA and PR⁺ patients may need closer follow up and more medical attention due to greater incidence and severity of PIPN.

https://ift.tt/2E1Dsfu

Anatomical basis for the choice of laparoscopic surgery for low rectal cancer through the pelvic imaging data—a cohort study

Abstract

Background

Low rectal cancer surgery without anus conservation needs permanent ileostomy or colostomy which seriously affects the quality of life of patients. Therefore, low rectal cancer surgery not only pays attention to the safety of surgical treatment but also to the anus conservation.

Methods

Sixty-seven patients suffering from low rectal cancer had undergone laparoscopic surgery which was analyzed through retrospective study. They were divided into the anus-conserving and non-anus-conserving groups. Thirty-five set of pelvic data was obtained from the preoperative CT and MRI images. After that, the discriminant function was obtained to predict the surgery methods for patients with low rectal carcinoma.

Results

Anal-conserving group discriminant function (F1) = − 33.698 + 6.045 × anal margin distance (cm) + 1.105 × T4; non-anus-conserving group discriminant function (F2) = − 14.125 + 3.138 × anal margin distance (cm) + 0.804 × T4. If F1 is greater than F2, then the case can be treated as the anus reservation while if F2 is greater than F1 the case cannot be treated anus reservation. The accuracy of the discriminant function was evaluated which was found to be 97%.

Conclusion

The discriminant function of pelvic data provides anatomical basis for the choice of surgical methods for low rectal cancer.

https://ift.tt/2IFGS6d

Magnetic Resonance Spectroscopy Features of the Visual Pathways in Patients with Glaucoma

Abstract

Purpose

The aim of the study was to investigate any metabolic changes on magnetic resonance spectroscopy (MRS) throughout the visual pathway of the brain in patients with glaucoma and a control group and correlate the results with clinical findings.

Material and Methods

A total of 87 patients were enrolled in the study, 30 healthy controls, 25 glaucoma, 16 suspected glaucoma (GS) and 16 ocular hypertension (OHT) patients. A single voxel MRS on TE 30 ms was performed by placing the volume of interest (VOI) on the corpus geniculatum laterale (CGL) and primary visual cortex (VC). Peak values of metabolites, such as N‑acetyl aspartate (NAA), creatine (Cr), choline (Cho) and Myo-inositol (Ins) were investigated on MRS. The MRS results were correlated with age, intraocular pressure (IOP), retinal nerve fiber length (RNFL), mean deviation (MD) and cup disk ratio (CD).

Results

The NAA values obtained from the CGL in glaucoma and GS cases were lower than the healthy control group. The Cho values at CGL in glaucoma were lower than GS and controls. There was a negative correlation between NAA values of the VC and CD in glaucoma cases. Additionally, there was a negative correlation between age and RNFL in both glaucoma and GS cases.

Conclusion

The use of MRS can reveal neurodegeneration in CGL and VC in patients with glaucoma. Depiction of metabolic changes throughout the visual pathways via MRS will guide the treatment planning and follow-up in glaucoma and GS cases.

https://ift.tt/2IG7oN1

Periodontal disease bacteria may kick-start Alzheimer's

Long-term exposure to periodontal disease bacteria causes inflammation and degeneration of brain neurons in mice that is similar to the effects of Alzheimer's disease in humans. Periodontal disease may be an initiator of Alzheimer's.

https://ift.tt/2zSQqZ5

Effect of machine learning methods on predicting NSCLC overall survival time based on Radiomics analysis

Abstract

Background

To investigate the effect of machine learning methods on predicting the Overall Survival (OS) for non-small cell lung cancer based on radiomics features analysis.

Methods

A total of 339 radiomic features were extracted from the segmented tumor volumes of pretreatment computed tomography (CT) images. These radiomic features quantify the tumor phenotypic characteristics on the medical images using tumor shape and size, the intensity statistics and the textures. The performance of 5 feature selection methods and 8 machine learning methods were investigated for OS prediction. The predicted performance was evaluated with concordance index between predicted and true OS for the non-small cell lung cancer patients. The survival curves were evaluated by the Kaplan-Meier algorithm and compared by the log-rank tests.

Results

The gradient boosting linear models based on Cox's partial likelihood method using the concordance index feature selection method obtained the best performance (Concordance Index: 0.68, 95% Confidence Interval: 0.62~ 0.74).

Conclusions

The preliminary results demonstrated that certain machine learning and radiomics analysis method could predict OS of non-small cell lung cancer accuracy.

https://ift.tt/2BXZWvh

Identifying patterns of care for elderly patients with non-surgically treated stage III non-small cell lung cancer: an analysis of the national cancer database

Abstract

Background

To compare patterns of care for elderly patients versus non-elderly patients with non-surgically treated stage III non-small cell lung cancer (NSCLC) using the National Cancer Database (NCDB). We hypothesize that elderly patients are less likely to receive curative treatments, including concurrent chemoradiation (CCRT), compared to non-elderly patients.

Methods

We identified patients from the NCDB between 2003 and 2014 with non-surgically treated stage III NSCLC. We defined elderly as ≥70 years old and non-elderly <70 years old. Treatment categories included: no treatment, palliative treatment (chemotherapy alone, radiation (RT) alone <59.4 Gy or chemoradiation (CRT) <59.4 Gy), or definitive treatment (RT alone ≥59.4 Gy or CRT ≥59.4 Gy). Differences in treatment between elderly and non-elderly were tested using the χ² test.

Results

We identified 57,602 elderly and 55,928 non-elderly patients. More elderly patients received no treatment (24.5% vs. 13.2%, P < 0.0001) and the elderly were less likely to receive definitive treatment (48.5% vs. 56.3%, P < 0.0001). CCRT was delivered in a significantly smaller proportion of elderly vs. non-elderly patients (66.0% vs. 78.9%, P < 0.0001 in patients treated with definitive intent; 32.0% vs. 44.5%, P < 0.0001 in patients receiving any treatment; and 24.2% vs. 38.6%, P < 0.0001 amongst all patients).

Conclusions

In this large study of patients with non-surgically treated stage III NSCLC, elderly patients were less likely to receive any treatment or treatment with definitive intent compared to the non-elderly. The lack of use of concurrent or sequential chemotherapy in the elderly with stage III NSCLC suggests that the optimal treatment approach for this vulnerable population remains undefined.

https://ift.tt/2CvDLO0

Japan Society of Gynecologic Oncology guidelines 2017 for the treatment of uterine cervical cancer

Abstract

The Japan Society of Gynecologic Oncology (JSGO) Guidelines 2017 for the Treatment of Uterine Cervical Cancer are for the purpose of providing standard treatment strategies for cervical cancer, indicating treatment methods currently considered appropriate for cervical cancer, minimizing variances in treatment methods among institutions, improving the safety of treatment and prognosis of diseases, reducing the economic and psychosomatic burden of patients by promoting performance of appropriate treatment, and enhancing mutual understanding between patients and healthcare professionals. The guidelines were prepared through consensus of the JSGO Guideline Committee, based on careful review of evidence gathered through the literature searches and in view of the medical health insurance system and actual clinical practice situations in Japan. The guidelines comprise eight chapters and five algorithms. The main features of the 2017 revision are as follows: (1) evidence was collected using a search formula and with cooperation of the Japan Library Association. The bibliographical search formula was placed at the end of the book; (2) regarding clinical questions (CQs) where evidence or clinical inspection in Japan was lacking, opinions of the Guidelines Committee were described as "proposals for future directions"; (3) cervical intraepithelial neoplasia (CIN) 3 and adenocarcinoma in situ (AIS) were treated as a cervical precancerous lesion; (4) the CQs of endoscopic surgery, radical trachelectomy, and sentinel node biopsy were newly added in Chapter 3, "primary treatment for stage IB–II cervical cancer"; and (5) the CQ about hormone replacement therapy after cancer treatment was newly established. Each recommendation is accompanied by a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here, we present the English version of the JSGO Guidelines 2017 for the Treatment of Uterine Cervical Cancer.

https://ift.tt/2RoSOxg