An economic evaluation of a multicomponent self-management intervention for adults with epilepsy (ZMILE study)

Summary

Objective

The objective of this (trial-based) economic evaluation was, from a societal perspective, to compare the cost-effectiveness of a multicomponent self-management intervention (MCI) with care as usual (CAU) in adult patients with epilepsy over a 12-month period.

Methods

In a randomized-controlled trial, participants were randomized into intervention or CAU group. Adherence, self-efficacy (Epilepsy Self-Efficacy Scale [ESES]), quality-adjusted life years (QALYs), healthcare costs, production losses, and patient and family costs were assessed at baseline and during the 12-month study period. Incremental cost-effectiveness ratios (ICERs) (i.e., cost per increased adherence, self-efficacy, or QALY), and cost-effectiveness acceptability curves were calculated.

Results

In total, 102 patients were included in the study, of whom 52 were in the intervention group. Adherence rates over 6 months were 63.7% for the CAU group and 75.9% for the intervention group. Adherence, ESES, and quality of life did not differ significantly between groups. An ICER of €54 per point increase in ESES score at 6 months and €1,105 per point increase at 12-month follow-up was found. The intervention resulted in an ICER of €88 per percentage of adherence increase at 6 months. ICERs of €8,272 and €15,144 per QALY gained were found at 6- and 12-month follow-up, respectively.

Significance

Although no statistically significant difference was found after baseline adjustments, cost-effectiveness estimates for MCI appear promising. As rules of inference are arbitrary, it has been argued that decisions should be based only on the net benefits, irrespective of whether differences are statistically significant. Hence, the MCI may be a cost-effective addition to the current standard care for adults with epilepsy.

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Particulate matter air pollution and liver cancer survival

Particulate matter (PM) air pollution exposure has been associated with cancer incidence and mortality especially with lung cancer. The liver is another organ possibly affected by PM due to its role in detoxifying xenobiotics absorbed from PM. Various studies have investigated the mechanistic pathways between inhaled pollutants and liver damage, cancer incidence, and tumor progression. However, little is known about the effects of PM on liver cancer survival. Twenty thousand, two hundred and twenty-one California Cancer Registry patients with hepatocellular carcinoma (HCC) diagnosed between 2000 and 2009 were used to examine the effect of exposure to ambient PM with diameter <2.5 μm (PM_2.5) on HCC survival. Cox proportional hazards models were used to estimate hazard ratios (HRs) relating PM_2.5 to all-cause and liver cancer-specific mortality linearly and nonlinearly—overall and stratified by stage at diagnosis (local, regional and distant)—adjusting for potential individual and geospatial confounders.PM_2.5 exposure after diagnosis was statistically significantly associated with HCC survival. After adjustment for potential confounders, the all-cause mortality HR associated with a 1 standard deviation (5.0 µg/m³) increase in PM_2.5 was 1.18 (95% CI: 1.16–1.20); 1.31 (95% CI:1.26–1.35) for local stage, 1.19 (95% CI:1.14–1.23) for regional stage, and 1.05 (95% CI:1.01–1.10) for distant stage. These associations were nonlinear, with substantially larger HRs at higher exposures. The associations between liver cancer-specific mortality and PM_2.5 were slightly attenuated compared to all-cause mortality, but with the same patterns.Exposure to elevated PM_2.5 after the diagnosis of HCC may shorten survival, with larger effects at higher concentrations.

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Noninvasive ventilation with helium–oxygen mixture in hypercapnic COPD exacerbation: aggregate meta-analysis of randomized controlled trials

When used as a driving gas during NIV in hypercapnic COPD exacerbation, a helium–oxygen (He/O2) mixture reduces the work of breathing and gas trapping. The potential for He/O2 to reduce the rate of NIV failure le...

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Low HDL levels in sepsis versus trauma patients in intensive care unit

The protective cardiovascular effect of high-density lipoproteins (HDLs) is considered to chiefly rely on reverse cholesterol transport from peripheral tissues back to the liver. However, HDL particles display...

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Progressive Entrustment to Achieve Resident Autonomy in the Operating Room: A National Qualitative Study With General Surgery Faculty and Residents

Objective: The purpose of this study was to identify behaviors that faculty and residents exhibit during intraoperative interactions, which support or inhibit progressive entrustment leading to operative autonomy. Background: In the operating room, a critical balance is sought between direct faculty supervision and appropriate increase in resident autonomy with indirect faculty supervision. Little is known regarding perspectives of faculty and residents about how attendings increasingly step back and safely delegate autonomy to trainees. Understanding the context in which these decisions are made is critical to achieving a safe strategy for imparting progressive responsibility. Methods: A qualitative study was undertaken from January 2014 to February 2015. Semistructured interviews were conducted with 37 faculty and 59 residents from 14 and 41 institutions, respectively. Participants were selected using stratified random sampling from general surgery residency programs across the United States to represent a range of university, university-affiliated, and community programs, and geographic regions. Audio recordings of interviews were transcribed, iteratively analyzed, and emergent themes identified. Results: Six themes were identified as influencing progressive entrustment in the operating room: optimizing faculty intraoperative feedback; policies and regulations affecting role of resident in the operating room; flexible faculty teaching strategies; context-specific variables; leadership opportunities for resident in the case; and safe struggle for resident when appropriate. Conclusions: Perspectives of faculty and residents while overlapping were different in emphasis. Better understanding faculty–resident interactions, individual behaviors, contextual influences, and national regulations that influence intraoperative education have the potential to significantly affect progressive entrustment in training paradigms.

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Editorial: the diminishing returns of normalisation of the oesophageal mucosa

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Ventilation through an extraglottic tracheal tube: a technique for deep extubation and airway control

Ventilation through an extraglottic tracheal tube: a technique for deep extubation and airway control

Wed, 07 Jun 2017 05:57:03 +0000

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Corrigendum

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Editorial: biologics in inflammatory bowel disease―time for direct comparisons

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Editorial: repeat duodenal biopsy for patients with coeliac disease―physician heal thyself and dietitian heal the patient!

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Editorial: the Millennium study cohort―evaluating environmental determinates of IBD in the 21st century

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Letter: sublingual dosing of tacrolimus in transplant patients―interesting concept to overcome first pass effects

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Letter: the efficacy of interferon-free regimens in HCV-related Child C cirrhosis needs careful interpretation

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Editorial: the diminishing returns of normalisation of the oesophageal mucosa―Authors' reply

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Editorial: functional dyspepsia―a disorder of duodenal permeability?

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Letter: sublingual dosing of tacrolimus in transplant patients―interesting concept to overcome first pass effects. Authors' reply

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Letter: determining the dominant role of environmental factors in UC development

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Editorial: should we recommend oesophageal biopsies for all patients with symptoms suggestive of GERD?

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Editorial: developing a stimulation test to identify FGF19 deficiency in bile acid diarrhoea

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Letter: should Barrett's oesophagus be considered a potential cardiovascular risk factor?

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Editors' declarations of interest

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Letter: determining the dominant role of environmental factors in UC development―Authors' reply

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Editorial: the Millennium study cohort―evaluating environmental determinates of IBD in the 21st Century. Authors' reply

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Editorial: non-alcoholic fatty liver disease―a pandemic in need of novel treatments and endpoints

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Editorial: tacrolimus―how low can you go?

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Letter: the efficacy of interferon-free regimens in HCV-related Child C cirrhosis needs careful interpretation―Authors' reply

http://ift.tt/2seAUn3

Emergency front-of-neck access: scalpel or cannula

,The parable of Buridan's ass

Wed, 07 Jun 2017 05:46:05 +0000

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

The combination of DEX and OND should be recommended in children with a high risk of POV.......Dexamethasone (DEX), ondansetron (OND) and droperidol (DRO) FOR Children undergoing elective surgery under general anaesthesia and considered at high risk for postoperative vomiting (POV)

The combination of DEX and OND should be recommended in children with a high risk of POV.........................................................................................................Dexamethasone (DEX), ondansetron (OND) and droperidol (DRO) FOR Children undergoing elective surgery under general anaesthesia and considered at high risk for postoperative vomiting (POV)

Wed, 07 Jun 2017 05:34:26 +0000

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Megalencephalic leukoencephalopathy with cysts: the Glialcam-null mouse model

Abstract

Objective

Megalencephalic leukoencephalopathy with cysts (MLC) is a genetic infantile-onset disease characterized by macrocephaly and white matter edema due to loss of MLC1 function. Recessive mutations in either MLC1 or GLIALCAM cause the disease. MLC1 is involved in astrocytic volume regulation; GlialCAM ensures the correct membrane localization of MLC1. Their exact role in brain ion-water homeostasis is only partly defined. We characterized Glialcam-null mice for further studies.

Methods

We investigated the consequences of loss of GlialCAM in Glialcam-null mice and compared GlialCAM developmental expression in mice and men.

Results

Glialcam-null mice had early-onset megalencephaly and increased brain water content. From 3 weeks, astrocytes were abnormal with swollen processes abutting blood vessels. Concomitantly, progressive white matter vacuolization developed due to intramyelinic edema. Glialcam-null astrocytes showed abolished expression of MLC1, reduced expression of the chloride channel ClC-2 and increased expression and redistribution of the water channel aquaporin4. Expression of other MLC1-interacting proteins and the volume regulated anion channel LRRC8A was unchanged. In mice, GlialCAM expression increased until 3 weeks and then stabilized. In humans, GlialCAM expression was highest in the first 3 years to then decrease and stabilize from approximately 5 years.

Interpretation

Glialcam-null mice replicate the early stages of the human disease with early-onset intramyelinic edema. The earliest change is astrocytic swelling, further substantiating that a defect in astrocytic volume regulation is the primary cellular defect in MLC. GlialCAM expression affects expression of MLC1, ClC-2 and aquaporin4, indicating that abnormal interplay between these proteins is a disease mechanism in megalencephalic leukoencephalopathy with cysts.

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Glioblastoma in natalizumab-treated multiple sclerosis patients

Abstract

We present two natalizumab-treated multiple sclerosis patients who developed glioblastoma multiforme (GBM) with variable outcomes. One patient had an isocitrate dehydrogenase (IDH)-wildtype GBM with aggressive behavior, who declined treatment and died 13 weeks after symptoms onset. The other patient underwent resection of an IDH-mutant secondary GBM that arose from a previously diagnosed grade II astrocytoma. He is still alive 5 years after the diagnosis of GBM. JC virus was not detected in either case. Whether natalizumab played a role in the development of GBM in those patients deserves further investigation.

http://ift.tt/2r4lZao

Beta-blocker use and fall risk in older individuals; original results from two studies with meta-analysis

Abstract

Aims

To investigate the association between use of beta-blockers and beta-blocker characteristics – selectivity, lipid solubility, intrinsic sympathetic activity (ISA), and CYP2D6 enzyme metabolism – and fall risk.

Methods

Data from two prospective studies were used, including community-dwelling individuals, N=7,662 (the Rotterdam Study) and 2,407 (B-PROOF), all aged ≥55 years. Fall incidents were recorded prospectively. Time-varying beta-blocker use was determined using pharmacy dispensing records. Cox proportional hazard models adjusted for age and sex were applied to determine the association between beta-blocker use, their characteristics – selectivity, lipid solubility, ISA, and CYP2D6 enzyme metabolism – , and fall risk. The results of the studies were combined using meta-analyses.

Results

In total 2,917 participants encountered a fall during a total follow-up time of 89,529 years. Meta-analysis indicated no association between use of any beta-blocker, compared to non-use, and fall risk, HR=0.97 (95%CI 0.88; 1.06). Neither was use of a selective beta-blocker associated with fall risk, HR=0.92 (95%CI 0.83; 1.01). Use of a non-selective beta-blocker was associated with an increased fall risk, HR=1.22 (95%CI 1.01; 1.48). Other beta-blocker characteristics including lipid solubility and CYP2D6 enzyme metabolism were not associated with fall risk.

Conclusion

Our study suggests that use of a non-selective beta-blocker, contrary to selective beta-blockers, is associated with an increased fall risk in an older population. In clinical practice, beta-blockers have been shown effective for a variety of cardiovascular indications. Though, fall risk should be considered when prescribing a beta-blocker in this age group, and the pros and cons for beta-blockers classes should be taken into consideration.

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Cervical cancer screening in the era of HPV vaccination: A review of shifting paradigms in cytopathology

Abstract

Significant changes in cervical cancer screening practice, guidelines, and prevention of cervical cancer have taken place in recent years including the raising of initial cervical cancer screening age, changes in frequency of cytology screening, and the adoption of high risk HPV and cytology co-testing for some patients; the introduction of the bivalent, quadrivalent, and 9-valent HPV vaccines; and the recent approval of high risk HPV testing as primary screening with the use of cytology as triage in positive cases. This review discusses the significance of primary HPV screening, the impact of HPV vaccination in the prevalence of cervical cancer and its precursors, the interplay between high risk HPV testing and vaccination, and the implications for clinical and cytological management. Future strategies for cervical screening in the post-vaccination era are also discussed.

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Investigation into the antimicrobial action and mechanism of a novel endogenous peptide β-casein 197 from human milk

A novel endogenous peptide cleaved from 197–213 AA of β-casein, named β-casein 197, was identified by tandem mass spectrometry. β-casein 197 constituted a significant proportion of the peptide content in prete...

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Identification of novel BCL11A variants in patients with epileptic encephalopathy: expanding the phenotypic spectrum

Abstract

BCL11A encodes a zinc finger protein that is highly expressed in hematopoietic tissues and the brain, and that is known to function as a transcriptional repressor of fetal hemoglobin (HbF). Recently, de novo variants in BCL11A have been reported in individuals with intellectual disability syndrome without epilepsy. In this study, we performed whole-exome sequencing of 302 patients with epileptic encephalopathies (EEs), and identified two novel BCL11A variants, c.577delC (p.His193Metfs*3) and c.2351A>C (p.Lys784Thr). Both patients shared major physical features characteristic of BCL11A-related intellectual disability syndrome, suggesting that characteristic physical features and the persistence of HbF should lead clinicians to suspect EEs caused by BCL11A pathogenic variants. Patient 1, with a frameshift variant, presented with Lennox–Gastaut syndrome, which expands the phenotypic spectrum of BCL11A haploinsufficiency. Patient 2, with a p.Lys784Thr variant, presented with West syndrome followed by drug-resistant focal seizures and more severe developmental disability. These two newly described patients contribute to delineating the associated, yet uncertain phenotypic characteristics of BCL11A disease-causing variants.

Graphical abstract

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Performance of BRCA1/2 mutation prediction models in male breast cancer patients

ABSTRACT

To establish whether existing mutation prediction models can identify which male breast cancer (MBC) patients should be offered BRCA1 and BRCA2 diagnostic DNA screening, we compared the performance of BOADICEA, BRCAPRO and the Myriad prevalence table ('Myriad').

These models were evaluated using the family data of 307 Dutch MBC probands tested for BRCA1/2, 58 (19%) of whom were carriers. We compared the numbers of observed versus predicted carriers and assessed the area under the receiver operating characteristic (ROC) curve (AUC) for each model.

BOADICEA predicted the total number of BRCA1/2 mutation carriers quite accurately (observed/predicted ratio: 0.94). When a cut-off of 10% and 20% prior probability was used, BRCAPRO showed a non-significant better performance (observed/predicted ratio BOADICEA: 0.81, 95% Confidence Interval (CI): (0.60-1.09) and 0.79, 95% CI: (0.57-1.09), vs. BRCAPRO: 1.02, 95% CI: (0.75-1.38) and 0.94, 95% CI: (0.68-1.31), respectively). Myriad underestimated the number of carriers in up to 69% of the cases. BRCAPRO showed a non-significant, higher AUC than BOADICEA (0.798 vs 0.776). Myriad showed a significantly lower AUC (0.671).

BRCAPRO and BOADICEA can efficiently identify MBC patients as BRCA1/2 mutation carriers. Besides their general applicability, these tools will be of particular value in countries with limited healthcare resources.

Graphical abstract

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Distinguishing pathogenic mutations from background genetic noise in cardiology: the use of large genome databases for genetic interpretation

ABSTRACT

Advances in clinical genetic testing has led to increased insight into the human genome, including how challenging it is to interpret rare genetic variation. In some cases, the ability to detect genetic mutations exceeds the ability to understand their clinical impact, limiting the advantage of these technologies. Obstacles in genomic medicine are many and include: understanding the level of certainty/uncertainty behind pathogenicity determination, the numerous different variant interpretation-guidelines used by clinical laboratories, delivering the certain or uncertain result to the patient, helping patients evaluate medical decisions in light of uncertainty regarding the consequence of the findings. Through publication of large publicly available exome/genome databases, researchers and physicians are now able to highlight dubious variants previously associated with different cardiac traits. Also, continuous efforts through data sharing, international collaborative efforts to develop disease-gene specific guidelines, and computational analyses using large data, will indubitably assist in better variant interpretation and classification. This paper discusses the current, and quickly changing, state of variant interpretation resources within cardiovascular genetic research, i.e. publicly available databases and ways of how cardiovascular genetic counsellors and geneticists can aid in improving variant interpretation in cardiology.

GRAPHICAL ABSTRACT

Distribution of the non-reference allele in SCN5A in Non-Finnish Europeans and African-Americans

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Participation trends in holistic movement practices: a 10-year comparison of yoga/Pilates and t’ai chi/qigong use among a national sample of 195,926 Australians

In recent decades, the evidence supporting the physical and mental health benefits of holistic movement practices such as yoga and t'ai chi have become increasingly established. Consequently, investigating the...

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Anti-obesity activity, acute toxicity, and chemical constituents of aqueous and ethanol Viola mandshurica extracts

Viola mandshurica has traditionally been used as an expectorant, diuretic, and anti-inflammatory drug. The present study was designed to test the hypothesis that low doses of two diffe...

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Comparison of Inching Electrodiagnosis Method and Ultrasonographic Findings in the Determination of Median Nerve Entrapment Site in Carpal Tunnel Syndrome.

Objective: The purpose of the study was to evaluate the diagnostic value of both inching method through the electrodiagnostic test and ultrasonographic assay in localizing the site of entrapment in patients with symptoms and signs of carpal tunnel syndrome. Design: Thirty-two hands with confirmed carpal tunnel syndrome through electrodiagnostic test and 30 hands as control group were enrolled. For both groups, sensory and motor latencies by inching technique and cross-sectional area by ultrasonography were measured at the inching points. The statistical analysis was performed by SPSS software, and mean difference with 95% confidence interval was calculated. Results: Mean of sensory peak latency with inching method and cross-sectional area by the ultrasonography was greater in case group compared with the control group (P

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The eSMART study protocol: a randomised controlled trial to evaluate electronic symptom management using the advanced symptom management system (ASyMS) remote technology for patients with cancer

Introduction

While some evidence exists that real-time remote symptom monitoring devices can decrease morbidity and prevent unplanned admissions in oncology patients, overall, these studies have significant methodological weaknesses. The electronic Symptom Management using the Advanced Symptom Management System (ASyMS) Remote Technology (eSMART) study is designed to specifically address these weaknesses with an appropriately powered, repeated-measures, parallel-group stratified randomised controlled trial of oncology patients.

Methods and analysis

A total of 1108 patients scheduled to commence first-line chemotherapy (CTX) for breast, colorectal or haematological cancer will be recruited from multiple sites across five European countries.

Patients will be randomised (1:1) to the ASyMS intervention (intervention group) or to standard care currently available at each site (control group). Patients in the control and intervention groups will complete a demographic and clinical questionnaire, as well as a set of valid and reliable electronic patient-reported outcome measures at enrolment, after each of their CTX cycles (up to a maximum of six cycles) and at 3, 6, 9 and 12 months after completion of their sixth cycle of CTX. Outcomes that will be assessed include symptom burden (primary outcome), quality of life, supportive care needs, anxiety, self-care self-efficacy, work limitations and cost effectiveness and, from a health professional perspective, changes in clinical practice (secondary outcomes).

Ethics and dissemination

Ethical approval will be obtained prior to the implementation of all major study amendments. Applications will be submitted to all of the ethics committees that granted initial approval.

eSMART received approval from the relevant ethics committees at all of the clinical sites across the five participating countries. In collaboration with the European Cancer Patient Coalition (ECPC), the trial results will be disseminated through publications in scientific journals, presentations at international conferences, and postings on the eSMART website and other relevant clinician and consumer websites; establishment of an eSMART website (www.esmartproject.eu) with publicly accessible general information; creation of an eSMART Twitter Handle, and production of a toolkit for implementing/utilising the ASyMS technology in a variety of clinical practices and other transferable health care contexts.

Trial registration number

NCT02356081.

http://ift.tt/2rSVqcq

Rehabilitation interventions to improve patient-reported outcomes and physical fitness in survivors of muscle invasive bladder cancer: a systematic review protocol

Introduction

Survivors of muscle invasive bladder cancer (MIBC) experience physical and psychosocial side effects of cancer diagnosis and treatment. These negative side effects have a crucial impact on their health-related quality of life (HRQoL). To date, there is evidence that rehabilitation interventions such as physical activity and psychosocial support have a positive effect on the HRQoL of cancer survivors. Unfortunately, there are no specific guidelines for rehabilitation or survivorship programmes for MIBC survivors. Therefore, this systematic review aims to assess the effects of exercise-based and psychosocial rehabilitation interventions in MIBC survivors.

Methods and analysis

The approach of this review is consistent with the Cochrane methodology. Randomized controlled trials and non-randomised studies will be included. The population of interest is patients (≥18 years of age) with diagnosis of MIBC or high-risk non-MIBC for whom a radical cystectomy is indicated. There will be two eligible intervention types for inclusion: exercise-based and psychosocial rehabilitation interventions. The primary outcome measures are patient-reported outcomes (eg, HRQoL, fatigue and pain) and physical fitness. Studies will be identified independently by two review authors by searching the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Web of Science and the Physiotherapy Evidence Database. A third reviewer will be asked by disagreements. Risk of bias will be assessed using the Cochrane Collaboration tool and the Newcastle-Ottawa Scale. Data will be summarised descriptively. If homogeneity of the studies is sufficient, meta-analysis will be undertaken. The broad scope of this review (ie, different interventions and study designs) is needed to have a comprehensive view on effective rehabilitation interventions.

Ethics and dissemination

Ethics approval is not required, as no primary data will be collected. Results will be disseminated through a peer-reviewed publication.

http://ift.tt/2rSNKad

The STOP-AB trial protocol: efficacy and safety of discontinuing patient antibiotic treatment when physicians no longer consider it necessary

Introduction

Since 2011, the Spanish Society of Family Medicine has recommended general practitioners (GPs) to ask their patients to stop taking antibiotics when they suspect a viral infection. However, this practice is seldom used because uncertainty about diagnosis, and fear of consequences of discontinuing antibiotic therapy, as well as perceived pressure to continue prescribing antibiotics and potential conflict with patients are more of a concern for GPs than antibiotic resistance. The main objective of this study is to determine whether discontinuation of antibiotic therapy when a GP no longer considers it necessary has any impact on the number of days with severe symptoms.

Methods and analysis

This is a multicentre, open-label, randomised controlled clinical trial. The study was conducted in 10 primary care centres in Spain. We included patients from 18 to 75 years of age with uncomplicated acute respiratory tract infections—acute rhinosinusitis, acute sore throat, influenza or acute bronchitis—who had previously taken any dose of antibiotic for <3 days, which physicians no longer considered necessary. The patients were randomly assigned to the usual strategy of continuing antibiotic treatment or to discontinuing antibiotic therapy. A sample size of 240 patients per group was calculated on the basis of a reduction of 1 day in the duration of severe symptoms being a clinically relevant outcome. The primary outcome was the duration of severe symptoms, that is, symptoms scored 5 or 6 by means of validated symptom diaries. Secondary outcomes included antibiotics taken, adverse events, patient satisfaction and complications within the first 3 months.

Ethics and dissemination

The study was approved by the Ethical Board of Fundació Jordi Gol i Gurina (reference number: 16/093). The findings of this trial will bedisseminated through research conferences and peer-reviewed journals.

Trial registration number

NCT02900820; pre-results.

http://ift.tt/2sQXW0e

Impact of iron fortification on the geospatial patterns of malaria and non-malaria infection risk among young children: a secondary spatial analysis of clinical trial data from Ghana

Objectives

Patterns of infection among children with varying levels of iron status in a malaria endemic area may vary spatially in ways requiring integrated infection and iron deficiency control programmes. The objective of this secondary analysis was to determine the geospatial factors associated with malaria and non-malaria infection status among young Ghanaian children at the end of a 5-month iron intervention trial.

Design

Cluster-randomised controlled trial.

Setting

Rural Ghana

Participants

1943 children (6–35 months of age) with geocoded compounds.

Interventions

Point-of-use fortification with micronutrient powders containing vitamins and minerals with or without iron.

Primary and secondary outcome measures

Generalised linear geostatistical models with a Matern spatial correlation function were used to analyse four infection response variables, defined using different combinations of inflammation (C-reactive protein, CRP >5 mg/L) and malaria parasitaemia. Analyses were also stratified by treatment group to assess the independent effects of the iron intervention.

Results

The by-group and combined-group analyses both showed that baseline infection status was the most consistent predictor of endline infection risk, particularly when infection was defined using parasitaemia. In the No-iron group, age above 24 months and weight-for-length z-score at baseline were associated with high CRP at endline. Higher asset score was associated with a 12% decreased odds of endline infection, defined as CRP >5 mg/L and/or parasitaemia (OR 0.88, 95% credible interval 0.78 to 0.98), regardless of group. Maps of the predicted risk and spatial random effects showed a defined low-risk area around the District centre, regardless of how infection was defined.

Conclusion

In a clinical trial setting of iron fortification, where all children receive treated bed nets and access to malaria treatment, there may be geographical variation in the risk of infection with distinct high-risk and low-risk areas, particularly around municipal centres.

Trial registration number

clinicaltrials.gov, NCT01001871.

http://ift.tt/2rSJXK0

Attitudes and behaviours of adolescents towards antibiotics and self-care for respiratory tract infections: a qualitative study

Background

To understand attitudes and behaviours of adolescents towards antibiotics, antimicrobial resistance and respiratory tract infections.

Design

Qualitative approach informed by the Theory of Planned Behaviour. Semi-structured interviews and focus groups were undertaken. We aimed to inform the development of an intervention in an international setting to improve antibiotic use among adolescents; therefore on completion of thematic analysis, findings were triangulated with qualitative data from similar studies in France, Saudi Arabia and Cyprus to elucidate differences in the behaviour change model and adaptation to diverse contexts.

Setting

7 educational establishments from the south of England.

Participants

53 adolescents (16–18 years) participated in seven focus groups and 21 participated in interviews.

Results

Most participants had taken antibiotics and likened them to other common medications such as painkillers; they reported that their peers treat antibiotics like a 'cure-all' and that they themselves were not interested in antibiotics as a discussion topic. They demonstrated low knowledge of the difference between viral and bacterial infections.Participants self-cared for colds and flu but believed antibiotics are required to treat other RTIs such as tonsillitis, which they perceived as more 'serious'. Past history of taking antibiotics for RTIs instilled the belief that antibiotics were required for future RTIs. Those who characterised themselves as 'non-science students' were less informed about antibiotics and AMR. Most participants felt that AMR was irrelevant to them and their peers. Some 'non-science' students thought resistance was a property of the body, rather than bacteria.

Conclusion

Addressing adolescents' misperceptions about antibiotics and the treatment of RTIs using a behaviour change intervention should help improve antibiotic awareness and may break the cycle of patient demand for antibiotics to treat RTIs amongst this group. Schools should consider educating all students in further education about antibiotic usage and AMR, not only those taking science.

http://ift.tt/2sQJiGn

Protocol for a randomised controlled trial of the effect of dapagliflozin, metformin and exercise on glycaemic variability, body composition and cardiovascular risk in prediabetes (the PRE-D Trial)

Introduction

The primary aim of this study is to compare the efficacy of three short-term glucose-lowering interventions (exercise, metformin and dapagliflozin) on glycaemic variability in overweight or obese men and women with elevated diabetes risk (ie, prediabetes, defined as haemoglobin A_1c (HbA_1c)39–47 mmol/mol / 5.7%–6.4%). The secondary aims are to investigate the effects of the interventions on body composition and cardiometabolic risk factors.

Methods and analysis

The Pre-D Trial is an investigator-initiated, randomised, controlled, parallel, open-label, superiority trial. The study aims to assign 120 participants in a 1:1:1:1 ratio to receive one of four interventions for 13 weeks: (1) dapagliflozin (10 mg once daily); (2) metformin (850 mg twice daily); (3) exercise (interval training, 5 days a week, 30 min per session); or (4) control (lifestyle advice). After the 13 weeks of intervention, a follow-up period of 13 weeks will follow to study the long-term effects of the interventions. The primary endpoint is reduction from baseline to end-of treatment (13 weeks) in mean amplitude of glycaemic excursions measured by continuous glucose monitoring. The secondary endpoints include concomitant changes in various measures of glucose metabolism, body weight, cardiorespiratory fitness, blood pressure, plasma lipids, objectively measured physical activity and dietary intake.

Ethics and dissemination

The study protocol has been approved by the Ethics Committee of the Capital Region and the Danish Medicines Agency. Approval of data and biobank storage has been obtained from the Danish Data Protection Board. The study will be carried out according to the Declaration of Helsinki and to the regulations for good clinical practice. The results from this trial will allow a number of research questions concerning the effect of exercise versus dapagliflozin or metformin in HbA_1c-defined prediabetes to be addressed.

Trial registration

NCT02695810

http://ift.tt/2rSvptN

Patient-reported outcome measures (PROMs) for assessing perceived listening effort in hearing loss: protocol for a systematic review

Introduction

In the UK, it is estimated that a disabling hearing loss (HL) affects 1 in 6 people. HL has functional, economic and social-emotional consequences for affected individuals. Intervention for HL focuses on improving access to the auditory signal using hearing aids or cochlear implants. However, even if sounds are audible and speech is understood, individuals with HL often report increased effort when listening.

Listening effort (LE) may be measured using self-reported measures such as patient-reported outcome measures (PROMs). PROMs are validated questionnaires completed by patients to measure their perceptions of their own functional status and well-being. When selecting a PROM for use in research or clinical practice, it is necessary to appraise the evidence of a PROM's acceptability to patients, validity, responsiveness and reliability.

Methods and analysis

A systematic review of studies evaluating the measurement properties of PROMs available to measure LE in HL will be undertaken. MEDLINE, EMBASE, CINAHL, PsychINFO and Web of Science will be searched electronically. Reference lists of included studies, key journals and the grey literature will be hand-searched to identify further studies for inclusion. Two reviewers will independently complete title, abstract and full-text screening to determine study eligibility. Data on the characteristics of each study and each PROM will be extracted. Methodological quality of the included studies will be appraised using the COnsensus-based Standards for the selection of health Measurement INstruments, the quality of included PROMs appraised and the credibility of the evidence assessed. A narrative synthesis will summarise extracted data.

Ethics and dissemination

Ethical permission is not required, as this study uses data from published research. Dissemination will be through publication in peer-reviewed journals, conference presentations and the lead author's doctoral dissertation. Findings may inform the selection of PROMs used to measure LE in HL.

http://ift.tt/2sQJh5h

Dyspnoea-12: a translation and linguistic validation study in a Swedish setting

Background

Dyspnoea consists of multiple dimensions including the intensity, unpleasantness, sensory qualities and emotional responses which may differ between patient groups, settings and in relation to treatment. The Dyspnoea-12 is a validated and convenient instrument for multidimensional measurement in English. We aimed to take forward a Swedish version of the Dyspnoea-12.

Methods

The linguistic validation of the Dyspnoea-12 was performed (Mapi Language Services, Lyon, France). The standardised procedure involved forward and backward translations by three independent certified translators and revisions after feedback from an in-country linguistic consultant, the developerand three native physicians. The understanding and convenience of the translated version was evaluated using qualitative in-depth interviews with five patients with dyspnoea.

Results

A Swedish version of the Dyspnoea-12 was elaborated and evaluated carefully according to international guidelines. The Swedish version, 'Dyspné–12', has the same layout as the original version, including 12 items distributed on seven physical and five affective items. The Dyspnoea-12 is copyrighted by the developer but can be used free of charge after permission for not industry-funded research.

Conclusion

A Swedish version of the Dyspnoea-12 is now available for clinical validation and multidimensional measurement across diseases and settings with the aim of improved evaluation and management of dyspnoea.

http://ift.tt/2rSSvAn

Bacterial meningitis in Finland, 1995-2014: a population-based observational study

Objectives

Bacterial meningitis remains an important cause of morbidity and mortality worldwide. Its epidemiological characteristics, however, are changing due to new vaccines and secular trends. Conjugate vaccines against Haemophilus influenzae type b and Streptococcus pneumoniae (10-valent) were introduced in 1986 and 2010 in Finland. We assessed the disease burden and long-term trends of five common causes of bacterial meningitis in a population-based observational study.

Methods

A case was defined as isolation of S. pneumoniae, Neisseria meningitidis, Streptococcus agalactiae, Listeria monocytogenes or H. influenzae from cerebrospinal fluid and reported to national, population-based laboratory surveillance system during 1995–2014. We evaluated changes in incidence rates (Poisson or negative binomial regression), case fatality proportions (²) and age distribution of cases (Wilcoxon rank-sum).

Results

During 1995–2014, S. pneumoniae and N. meningitidis accounted for 78% of the total 1361 reported bacterial meningitis cases. H. influenzae accounted for 4% of cases (92% of isolates were non-type b). During the study period, the overall rate of bacterial meningitis per 1 00 000 person-years decreased from 1.88 cases in 1995 to 0.70 cases in 2014 (4% annual decline (95% CI 3% to 5%). This was primarily due to a 9% annual reduction in rates of N. meningitidis (95% CI 7% to 10%) and 2% decrease in S. pneumoniae (95% CI 1% to 4%). The median age of cases increased from 31 years in 1995–2004 to 43 years in 2005–2014 (p=0.0004). Overall case fatality proportion (10%) did not change from 2004 to 2009 to 2010–2014.

Conclusions

Substantial decreases in bacterial meningitis were associated with infant conjugate vaccination against pneumococcal meningitis and secular trend in meningococcal meningitis in the absence of vaccination programme. Ongoing epidemiological surveillance is needed to identify trends, evaluate serotype distribution, assess vaccine impact and develop future vaccination strategies.

http://ift.tt/2sQGngM

A cross-sectional study measuring vanadium and chromium levels in paediatric patients with CKD

Objectives

Although many secondary effects of high levels of vanadium (V) and chromium (Cr) overlap with symptoms seen in paediatric patients with chronic kidney disease (CKD), their plasma V and Cr levels are understudied.

Design

Ancillary cross-sectional study to a prospective, longitudinal, randomised controlled trial.

Setting

Children's Hospital of Western Ontario, London Health Sciences Centre, London, Ontario, Canada.

Participants

36 children and adolescents 4–18 years of age with CKD.

Interventions

1–6 trace element measurements per patient. Cystatin C (CysC) estimated glomerular filtration rate (eGFR) was calculated using the Filler formula. Plasma V and Cr levels were measured using high-resolution sector field inductively coupled mass spectrometry. Anthropomorphic data and blood parameters were collected from our electronic chart programme. Water Cr and V data were obtained from the Ontario Water (Stream) Quality Monitoring Network.

Primary and secondary outcome measures

Primary outcomes: plasma Cr and V. Secondary outcomes: age, season, CysC, CysC eGFR, and Cr and V levels in environmental water.

Results

The median (IQR) eGFR was 51 mL/min/1.73 m² (35, 75). The median V level was 0.12 µg/L (0.09, 0.18), which was significantly greater than the 97.5th percentile of the reference interval of 0.088 µg/L; 32 patients had at least one set of V levels above the published reference interval. The median Cr level was 0.43 µg/L (0.36, 0.54), which was also significantly greater than the established reference interval; 34 had at least one set of Cr levels above the published reference interval. V and Cr levels were moderately correlated. Only some patients had high environmental exposure.

Conclusions

Our study suggests that paediatric patients with CKD have elevated plasma levels of V and Cr. This may be the result of both environmental exposure and a low eGFR. It may be necessary to monitor V and Cr levels in patients with an eGFR <30 mL/min/1.73 m².

Trial registration number

NCT02126293; HC#172241.

http://ift.tt/2rSNl7C

The influence of multisite pain and psychological comorbidity on prognosis of chronic low back pain: longitudinal data from the Norwegian HUNT Study

Objectives

This study aimed to investigate the prospective influence of multisite pain, depression, anxiety, self-rated health and pain-related disability on recovery from chronic low back pain (LBP).

Setting

The data is derived from the second (1995–1997) and third (2006–2008) wave of the Nord-Trøndelag Health Study (HUNT) in Norway.

Participants

The study population comprises 4484 women and 3039 men in the Norwegian HUNT Study who reported chronic LBP at baseline in 1995–1997.

Primary outcome measures

The primary outcome was recovery from chronic LBP at the 11-year follow-up. Persons not reporting pain and/or stiffness for at least three consecutive months during the last year were defined as recovered. A Poisson regression model was used to estimate adjusted risk ratios (RRs) with 95% CIs.

Results

At follow-up, 1822 (40.6%) women and 1578 (51.9%) men reported recovery from chronic LBP. The probability of recovery was inversely associated with number of pain sites (P-trend<0.001). Compared with reporting 2–3 pain sites, persons with only LBP had a slightly higher probability of recovery (RR 1.10, 95% CI 0.98 to 1.22 in women and RR 1.10, 95% CI 1.01 to 1.21 in men), whereas people reporting 6–9 pain sites had substantially lower probability of recovery (RR 0.58, 95% CI 0.52 to 0.63 in women and RR 0.70, 95% CI 0.63 to 0.79 in men). Poor/not so good self-rated general health, symptoms of anxiety and depression, and pain-related disability in work and leisure were all associated with reduced probability of recovery, but there was no statistical interaction between multisite pain and these comorbidities.

Conclusions

Increasing number of pain sites was inversely associated with recovery from chronic LBP. In addition, factors such as poor self-rated health, psychological symptoms and pain-related disability may further reduce the probability of recovery from chronic LBP.

http://ift.tt/2sQSo5M

A systematic review of alcohol screening and assessment measures for young people: a study protocol

Introduction

Alcohol consumption creates a significant public health burden, and young people who drink alcohol place themselves at risk of harm. Expert guidance and reviews have highlighted the pressing need for reliable and valid, age-appropriate alcohol screening and assessment measures for young people. The proposed systematic review will evaluate existing alcohol screening and assessment measures for young people aged 24 and under.

Methods and analysis

Six electronic databases will be searched for published and grey literature. In addition, reverse and forward citation searching and consultation with experts will be performed. Three sets of search terms will be combined, including alcohol use/problems, young people and validation studies. The titles and abstracts of reports from the searches will be screened, and potentially relevant full-text reports will be retrieved and independently assessed for inclusion by two reviewers based on prespecified criteria. Discrete validation studies within included reports will then be assessed for eligibility. There will be an a priori basic quality threshold for predictive validity, internal and test–retest for studies to warrant full data extraction. Studies above the quality threshold will be assessed for quality using the modified consensus-based standards for the selection of health measurement instruments checklist and a quality assessment tool for diagnostic accuracy studies.

Dissemination

This review will highlight the best performing measures both for screening and assessment based on their psychometric properties and the quality of the validation studies supporting their use. Providing clear guidance on which existing measures perform best to screen and assess alcohol use and problems in young people will inform policy, practice and decision-making, and clarify the need for further research.

Trial registration number

International Prospective Register of Systematic Reviews, CRD42016053330.

http://ift.tt/2sQTezC

Evaluating the short-term and long-term effects of an internet-based aural rehabilitation programme for hearing aid users in general clinical practice: a randomised controlled trial

Objective

Guided internet-based intervention beyond hearing aid (HA) fitting has been shown to be efficacious in randomised controlled trials (RCTs). However, internet interventions have rarely been applied clinically as a part of regular aural rehabilitation (AR). Our aim was to evaluate the effectiveness of internet-based AR for HA users from a clinical population.

Outcome measures

The Hearing Handicap Inventory for the Elderly (HHIE) was used as the primary outcome measure, and the Communication Strategies Scale (CSS) and the Hospital Anxiety and Depression Scale were used as secondary outcome measures. All questionnaires were administered before and directly after the intervention and at 6 months postintervention.

Methods

We used a parallel group design (RCT). The data were collected in 2013–2014 at three different clinics. Seventy-four HA users were randomly assigned to receive either full internet-based AR (intervention group, n=37) or one element of the internet-based AR (control group, n=37).

Results

Data were analysed following the intention-to-treat principle. Each group showed improved HHIE scores over time and did not differ significantly from each other. The intervention group showed significantly greater improvement compared with the control group for the CSS total and the non-verbal subscale scores. The intervention group and control group were also subdivided into two age groups: 20–59 years and 60–80 years. Significantly better improvement on the CSS total and non-verbal subscale scores was found in the older group compared with the younger participants.

Conclusions

This study indicates that participants in an internet-based intervention applied in general clinical practice showed improved self-reported communication skills compared with a control group. Receiving a full intervention was not more effective in improving self-reported hearing problems than receiving just one element of the internet-based intervention.

Trial registration number

This trial is registered at ClinicalTrals.gov, NCT01837550; results.

http://ift.tt/2rSSDQD

Utilising advance care planning videos to empower perioperative cancer patients and families: a study protocol of a randomised controlled trial

Introduction

Despite positive health outcomes associated with advance care planning (ACP), little research has investigated the impact of ACP in surgical populations. Our goal is to evaluate how an ACP intervention video impacts the patient centredness and ACP of the patient-surgeon conversation during the presurgical consent visit. We hypothesise that patients who view the intervention will engage in a more patient-centred communication with their surgeons compared with patients who view a control video.

Methods and analysis

Randomised controlled superiority trial of an ACP video with two study arms (intervention ACP video and control video) and four visits (baseline, presurgical consent, postoperative 1 week and postoperative 1 month). Surgeons, patients, principal investigator and analysts are blinded to the randomisation assignment.

Setting

Single, academic, inner city and tertiary care hospital. Data collection began July 16, 2015 and continues to March 2017.

Participants

Patients recruited from nine surgical oncology clinics who are undergoing major cancer surgery.

Interventions

In the intervention arm, patients view a patient preparedness video developed through extensive engagement with patients, surgeons and other stakeholders. Patients randomised to the control arm viewed an informational video about the hospital surgical programme.

Main outcomes and measures

Primary Outcome: Patient centredness and ACP of patient-surgeon conversations during the presurgical consent visit as measured through the Roter Interaction Analysis System. Secondary outcomes: patient Hospital Anxiety and Depression Scale score; patient goals of care; patient, companion and surgeon satisfaction; video helpfulness; medical decision maker designation; and the frequency patients watch the video. Intent-to-treat analysis will be used to assess the impact of video assignment on outcomes. Sensitivity analyses will assess whether there are differential effects contingent on patient or surgeon characteristics.

Ethics and dissemination

This study has been approved by the Johns Hopkins School of Medicine institutional review board and is registered on clinicaltrials.gov (NCT02489799, First received: July 1, 2015).

Trial registration number

clinicaltrials.gov, NCT02489799.

http://ift.tt/2sR1qjn

B7-H4 is a prognostic biomarker for poor survival in patients with pancreatic cancer

B7-H4 belongs to the immune costimulatory B7 family and is thought to negatively regulate T-cell mediated immunity, and may contribute an important role in tumor immune evasion. Although the expression of B7-H4 has been observed in human pancreatic cancer, the prognostic significance of this expression is poorly understood. This present study explored the prognostic value of B7-H4 in pancreatic cancer. Patients with pancreatic cancer and healthy controls were recruited at the Second Affiliated Hospital to Zhejiang University from January 2011 to December 2014.

http://ift.tt/2sCcy48

Sending CAR T Cells After Multiple Myeloma [News in Brief]

Investigational BCMA-targeting therapy shows early promise, inducing complete, durable responses.

http://ift.tt/2rz9mYu

Dual HER2 Blockade Helps Prevent Breast Cancer Return [News in Brief]

The addition of pertuzumab to trastuzumab reduces the incidence of recurrence following surgery.

http://ift.tt/2r4bO5H

Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-grade Ovarian Carcinoma [Research Briefs]

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations.

http://ift.tt/2rzcOCE

A multicenter evaluation of biochemical relapse free survival outcomes for intra-operatively planned prostate brachytherapy using an automated delivery system

This multicentre analysis shows evidence for efficacy in brachytherapy treatments for prostate cancer when delivered using an automated delivery system. Results with this technique do not appear inferior to other published series on preplanned techniques.

http://ift.tt/2sC18h1

Phase I-II Study of Dual-Energy Computed Tomography (DECT) for Assessment of Pulmonary Function in Radiotherapy Planning

This prospective study evaluated the role of DECT-iodine maps for the assessment of lung function in radiotherapy planning. Using a 2-material decomposition method, iodine concentration of whole lung volume was used as an indicator of regional perfusion. DECT-iodine map provided accurate lung function information. Significant differences in mean and low dose to whole vs. functional lung volumes were found with integration of DECT-iodine maps in early and advanced stage lung cancer radiotherapy planning.

http://ift.tt/2sC0n7l

Prospective clinical implementation of a novel MR-tracking device for real-time HDR brachytherapy catheter positioning

We explored the role of MRTR in a prospective clinical trial. Eleven gynecologic cancer patients underwent MRTR to rapidly optimize interstitial catheter placement. MRTR catheter tip location and orientation were computed and overlaid on images displayed on in-room monitors. MRTR-based navigation resulted in rapid and optimal placement of interstitial brachytherapy catheters.

http://ift.tt/2s2dUYZ

Lung cancer samples preserved in liquid medium: One step beyond cytology

Abstract

Lung cancer is one of the most common cancer types in men and women worldwide with a high mortality rate. World Health Organization (WHO) classification has accepted biopsy as the primary sample for lung cancer diagnosis, pathological classification and molecular testing for management of patients, yet, the use of alternative sampling procedures is highly encouraged. Bronchial cytological samples require a less invasive collection technique and may be suitable for pathological and molecular analysis and storage in liquid medium. Furthermore, the molecular analysis of bronchial cytological samples allows the detection of molecular biomarkers, which may be useful for the selection of molecular targeted therapies. Thus, the purpose of this review is to describe the usefulness of bronchial cytological samples preserved in liquid medium from lung cancer patients for pathological diagnosis and molecular investigation.

http://ift.tt/2qZHPB1

Laparoscopic total pancreatectomy for multiple endocrine neoplasia type 1 syndrome-associated multifocal, non-functioning pancreatic neuroendocrine tumor: A case report

Abstract

Pancreatic neuroendocrine tumors are rare, accounting for less than 3% of all pancreatic tumors. Although laparoscopic pancreas-preserving surgery for managing sporadic pancreatic neuroendocrine tumors has been described in the literature, laparoscopic total pancreatectomy has rarely been reported. We present a 30-year-old man who was incidentally diagnosed with multiple endocrine neoplasia type 1 syndrome with parathyroid hyperplasia and a non-functioning pancreatic neuroendocrine tumor. He underwent laparoscopic total pancreatectomy with splenectomy. This report highlights the technical details of laparoscopic total pancreatectomy, which appears to be a feasible and safe option in select cases.

http://ift.tt/2sBTSkY

Non-invasive papillary urothelial carcinoma of the vagina: molecular analysis of a rare case identifies clonal relationship to non-invasive urothelial carcinoma of the bladder

Abstract

We present a rare case of non-invasive papillary urothelial carcinoma of the vagina as the initial presentation of a multicentric urothelial carcinoma also involving bladder and renal pelvis and report for the first time in the literature the molecular alterations observed in the vaginal urothelial lesion and the synchronous lesions of the urinary tract. In this case, the non-invasive papillary urothelial carcinoma in the vagina displayed the same genetic alterations in the FGFR3 and PIK3CA genes as those seen in the non-invasive papillary urothelial carcinoma of the bladder contrasting with the wild phenotype observed in the invasive urothelial carcinoma of the renal pelvis. This observation could reinforce the theory of "seeding" of carcinoma cells as a valid and most likely explanation of this multifocality. In addition, we emphasize in this report the importance of recognizing this rare lesion in the female genital tract and its differential diagnosis.

http://ift.tt/2s2azZQ

Surveillance of surgical site infections by Pseudomonas aeruginosa and strain characterization in Tanzanian hospitals does not provide proof for a role of hospital water plumbing systems in transmission

The role of hospital water systems in the development of Pseudomonas aeruginosa (P. aeruginosa) surgical site infections (SSIs) in low-income countries is barely studied. This study characterized P. aeruginosa is...

http://ift.tt/2rSrGMU

Virulence traits associated with Burkholderia cenocepacia ST856 epidemic strain isolated from cystic fibrosis patients

Burkholderia cenocepacia is considered one of the most problematic cystic fibrosis (CF) pathogens. Colonization prevalence in the Serbian CF population is high and virtually exclusivel...

http://ift.tt/2rSxypu

Advances in Microbiology Vol.7,No.5 (May 2017)

Different Preservation Methods for Long Term Maintenance of Haemophilus influenzae
H. influenzae, Preservation Methods, Culture Media
Paper Information Full Paper: PDF (Size:1135KB)
DOI: 10.4236/aim.2017.75028

High Ethanol Production by Marine-Derived Yeasts-Saccharomyces cerevisiae under Stress Pressures
Marine-Derived Yeast, Fermentation, Bioethanol, Coastal Water, Saccharomyces cerevisiae, Stress Pressure
Paper Information Full Paper: PDF (Size:384KB)
DOI: 10.4236/aim.2017.75029

Effect of Lactate and Starter Inoculum on Biogas Production from Fresh Maize and Maize Silage
Biogas, Lactic Acid, Maize, Silage, Starter Inoculum
Paper Information Full Paper: PDF (Size:1797KB)
DOI: 10.4236/aim.2017.75030

Microorganisms Associated with Vegetable Oil Polluted Soil
Microorganisms, Degradation, Vegetable Oil Spill, Lipolytic Activity
Paper Information Full Paper: PDF (Size:296KB)
DOI: 10.4236/aim.2017.75031

Continuous Saccharification of Laminarin by Immobilized Laminarinase ULam111 Followed by Ethanol Fermentation with a Marine-Derived Yeast
Laminarin, Laminarinase, β-1,3-Glucanase, Immobilization, Ethanol Fermentation
Paper Information Full Paper: PDF (Size:1977KB)
DOI: 10.4236/aim.2017.75032

http://ift.tt/1lkzXmf

The Interaction of Selectins and PSGL-1 as a Key Component in Thrombus Formation and Cancer Progression

Cellular interaction is inevitable in the pathomechanism of human disease. Formation of heterotypic cellular aggregates, between distinct cells of hematopoietic and nonhematopoietic origin, may be involved in events leading to inflammation and the complex process of cancer progression. Among adhesion receptors, the family of selectins with their ligands have been considered as one of the major contributors to cell-cell interactions. Consequently, the inhibition of the interplay between selectins and their ligands may have potential therapeutic benefits. In this review, we focus on the current evidence on the selectins as crucial modulators of inflammatory, thrombotic, and malignant disorders. Knowing that there is promiscuity in selectin binding, we outline the importance of a key protein that serves as a ligand for all selectins. This dimeric mucin, the P-selectin glycoprotein ligand 1 (PSGL-1), has emerged as a major player in inflammation, thrombus, and cancer development. We discuss the interaction of PSGL-1 with various selectins in physiological and pathological processes with particular emphasis on mechanisms that lead to severe disease.

http://ift.tt/2sBqr2v

White Matter Injury and Recovery after Hypertensive Intracerebral Hemorrhage

Hypertensive intracerebral hemorrhage (ICH) could very probably trigger white matter injury in patients. Through the continuous study of white matter injury after hypertensive ICH, we achieve a more profound understanding of the pathophysiological mechanism of its occurrence and development. At the same time, we found a series of drugs and treatment methods for the white matter repair. In the current reality, the research paradigm of white matter injury after hypertensive ICH is relatively obsolete or incomplete, and there are still lots of deficiencies in the research. In the face of the profound changes of stroke research perspective, we believe that the combination of the lenticulostriate artery, nerve nuclei of the hypothalamus-thalamus-basal ganglia, and the white matter fibers located within the capsula interna will be beneficial to the research of white matter injury and repair. This paper has classified and analyzed the study of white matter injury and repair after hypertensive ICH and also rethought the shortcomings of the current research. We hope that it could help researchers further explore and study white matter injury and repair after hypertensive ICH.

http://ift.tt/2sC5TXG

Virtopsy shows a high status funerary treatment in an early 18th Dynasty non-royal individual

Abstract

This work presents the multidisciplinary investigation of the head of Nebiri (Museo Egizio, Turin S_5109), Chief of Stables, a high status elite person from the 18th Dynasty involving MDCT, 3D brain surface and facial reconstructions accompanied by a consideration of previously presented chemical analysis of the embalming materials found in fragments of bandages used on the head and viscera (lung) found in one of the four canopic jars. Comparison of the techniques used for the cosmetic treatment of Nebiri with those used in other elite and high status non-royal persons confirms the validity of the use of the term "high status elite" in the case of Nebiri. This case highlights the importance of using modern forensic techniques both to enhance new technologies of retrospective diagnosis on altered human remains and to increase knowledge of past populations.

http://ift.tt/2qZy9GL

Unexpected brain finding in pre-autopsy postmortem CT

Abstract

A case is presented in which pre-autopsy postmortem computed tomography (PMCT) revealed an unexpected brain abscess with a related frontal sinusitis and an erosion of the posterior wall of the frontal sinus. PMCT findings enabled the forensic pathologists to adapt protective measures during autopsy and protect their health from infection. Pre-autopsy PMCT has been also useful in the early differential diagnosis procedure. The complementary use of postmortem imaging and autopsy can improve the quality of forensic death investigations.

http://ift.tt/2rJORa2

Index cholecystectomy in a rural hospital: it can be done

Background

Index cholecystectomy (IC) refers to an operation during a patient's first hospital admission with symptomatic gallstone (GS) disease. There are proven reductions in cost, hospital bed days and GS-related complications while awaiting elective surgery. IC has not been universally adopted, particularly in smaller centres where logistics can present a barrier. The aim of this paper is to describe the introduction of routine IC at Hastings Hospital and the effects in terms of waiting time until surgery; GS-related re-presentations and complications while awaiting surgery; operative complications and overall hospital stay.

Methods

Data were collected for all patients who underwent cholecystectomy in the year following the introduction of IC (2015/2016). The results were compared with data from the year 2009/2010.

Results

A total of 259 cholecystectomies were performed over the 2015/2016 study period compared with 186 in the 2009/2010 study period. The IC rate increased from 9.89% in 2009 to 75.4% in 2015 (P < 0.001). The incidence of GS pancreatitis whilst waiting for surgery reduced from six in 2015 compared with one in 2009 (P = 0.046). The operative complications were similar in both groups. Total hospital stay was also similar.

Conclusion

The study shows that it is possible to perform IC in a rural setting reducing complications of waiting and in particular, rates of GS-related pancreatitis were significantly reduced. It can be done safely with an accommodating acute on-call system.

http://ift.tt/2s2byJy

Finnish Subacromial Impingement Arthroscopy Controlled Trial (FIMPACT): a protocol for a randomised trial comparing arthroscopic subacromial decompression and diagnostic arthroscopy (placebo control), with an exercise therapy control, in the treatment of shoulder impingement syndrome

Introduction

Arthroscopic subacromial decompression (ASD) is the most commonly performed surgical intervention for shoulder pain, yet evidence on its efficacy is limited. The rationale for the surgery rests on the tenet that symptom relief is achieved through decompression of the rotator cuff tendon passage. The primary objective of this superiority trial is to compare the efficacy of ASD versus diagnostic arthroscopy (DA) in patients with shoulder impingement syndrome (SIS), where DA differs only by the lack of subacromial decompression. A third group of supervised progressive exercise therapy (ET) will allow for pragmatic assessment of the relative benefits of surgical versus non-operative treatment strategies.

Methods and Analysis

Finnish Subacromial Impingement Arthroscopy Controlled Trial is an ongoing multicentre, three-group randomised controlled study. We performed two-fold concealed allocation, first by randomising patients to surgical (ASD or DA) or conservative (ET) treatment in 2:1 ratio and then those allocated to surgery further to ASD or DA in 1:1 ratio. Our two primary outcomes are pain at rest and at arm activity, assessed using visual analogue scale (VAS). We will quantify the treatment effect as the difference between the groups in the change in the VAS scales with the associated 95% CI at 24 months. Our secondary outcomes are functional assessment (Constant score and Simple shoulder test), quality of life (15D and SF-36), patient satisfaction, proportions of responders and non-responders, reoperations/treatment conversions, all at 2 years post-randomisation, as well as adverse effects and complications. We recruited a total of 210 patients from three tertiary referral centres. We will conduct the primary analysis on the intention-to-treat basis.

Ethics and Dissemination

The study was approved by the Institutional Review Board of the Pirkanmaa Hospital District and duly registered at ClinicalTrials.gov. The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations.

Trial registration number

NCT00428870; Pre-results.

http://ift.tt/2sdP3Be

Inhibition of neurotensin receptor 1 induces intrinsic apoptosis via let-7a-3p/Bcl-w axis in glioblastoma

http://ift.tt/2rSArGD

The differential expression of omega-3 and omega-6 fatty acid metabolising enzymes in colorectal cancer and its prognostic significance

http://ift.tt/2sQbRnh

Phase I dose-escalation studies of roniciclib, a pan-cyclin-dependent kinase inhibitor, in advanced malignancies

http://ift.tt/2sQeVzI

Herpes zoster risk after 21 specific cancers: population-based case–control study

http://ift.tt/2rSsscW

A meta-analysis comparing the risk of metastases in patients with rectal cancer and MRI-detected extramural vascular invasion (mrEMVI) vs mrEMVI-negative cases

http://ift.tt/2sQ318T

Clinical value of R-spondins in triple-negative and metaplastic breast cancers

http://ift.tt/2rSi5FW

Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study

http://ift.tt/2sQkmOY

Pre-diagnosis diet and survival after a diagnosis of ovarian cancer

http://ift.tt/2rSi2de

Nomogram-based prediction of survival in patients with advanced oesophagogastric adenocarcinoma receiving first-line chemotherapy: a multicenter prospective study in the era of trastuzumab

http://ift.tt/2sQbR6L

One-carbon metabolism in cancer

http://ift.tt/2rSiB6L

Comorbid conditions delay diagnosis of colorectal cancer: a cohort study using electronic primary care records

http://ift.tt/2sQtymA

BAG-1 as a biomarker in early breast cancer prognosis: a systematic review with meta-analyses

http://ift.tt/2rSyDxg

Efficacy and safety of gemcitabine plus S-1 in pancreatic cancer: a pooled analysis of individual patient data

http://ift.tt/2sQldPN

Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer

http://ift.tt/2rSs7Ha

GP participation in increasing uptake in a national bowel cancer screening programme: the PEARL project

http://ift.tt/2sQnlHn

Sequencing of DICER1 in sarcomas identifies biallelic somatic DICER1 mutations in an adult-onset embryonal rhabdomyosarcoma

http://ift.tt/2rSHLSR

Efficacy of anti-PD-1 therapy in patients with melanoma brain metastases

http://ift.tt/2sQbY1R

The contribution of body mass index to appraisal delay in colorectal cancer diagnosis: a structural equation modelling study

http://ift.tt/2rSlyEr

Mutation status among patients with sinonasal mucosal melanoma and its impact on survival

http://ift.tt/2sQnhaB

Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study

http://ift.tt/2rSdd3w

A Phase 1 Study of LY2874455, an Oral Selective pan-FGFR Inhibitor, in Patients with Advanced Cancer

Abstract

Background

We report here a phase 1 study of LY2874455, a potent oral selective pan-fibroblast growth factor receptor (FGFR) inhibitor.

Objective

The primary objective was to determine the recommended phase 2 dosing (RP2D). Secondary objectives included determining toxicity, antitumor activity, pharmacokinetics (PK), and pharmacodynamic (PD) properties of LY2874455.

Patients and Methods

This study comprised two parts: (a) dose escalation with 3 + 3 cohorts in patients with solid tumors and (b) dose-expansion cohorts in patients with gastric cancer (GC) and non-small cell lung cancer (NSCLC). Part A: 36 patients in 11 dose cohorts ranging from 2 to 24 mg twice daily (BID). RP2D was 16 mg BID. Part B: GC cohort, 29 patients, NSCLC cohort, 27 patients, all treated at the RP2D.

Results

LY2874455 was slowly absorbed and generally showed linear PK. The effective half-life was ∼12 h. PD properties of LY2874455 occurred at doses ≥10 mg by increases in serum phosphorus. Phosphate binders were administered to control serum phosphorus. LY2874455 was generally well tolerated; most toxicities were grade 1 or 2; most frequent were hyperphosphatemia, diarrhea, and stomatitis. Efficacy: part A: 24 patients evaluable: 1 patient in the 14-mg BID cohort with GC had a partial response (PR); 14 patients had stable disease (SD); part B: NSCLC cohort: 11 of 12 evaluable patients had SD; GC cohort: 15 patients evaluable: 1 patient with PR; 12 patients with SD.

Conclusions

LY2874455 has an RP2D of 16 mg BID and demonstrated good tolerability and activity in solid-organ cancer patients. The role of FGFR inhibition on tumor growth in patients requires further study. (NCT01212107).

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Synthesis and Characterization of Novel BMI1 Inhibitors Targeting Cellular Self-Renewal in Hepatocellular Carcinoma

Abstract

Background

Hepatocellular carcinoma (HCC) represents one of the most lethal cancers worldwide due to therapy resistance and disease recurrence. Tumor relapse following treatment could be driven by the persistence of liver cancer stem-like cells (CSCs). The protein BMI1 is a member of the polycomb epigenetic factors governing cellular self-renewal, proliferation, and stemness maintenance. BMI1 expression also correlates with poor patient survival in various cancer types.

Objective

We aimed to elucidate the extent to which BMI1 can be used as a potential therapeutic target for CSC eradication in HCC.

Methods

We have recently participated in characterizing the first known pharmacological small molecule inhibitor of BMI1. Here, we synthesized a panel of novel BMI1 inhibitors and examined their ability to alter cellular growth and eliminate cancer progenitor/stem-like cells in HCC with different p53 backgrounds.

Results

Among various molecules examined, RU-A1 particularly downregulated BMI1 expression, impaired cell viability, reduced cell migration, and sensitized HCC cells to 5-fluorouracil (5-FU) in vitro. Notably, long-term analysis of HCC survival showed that, unlike chemotherapy, RU-A1 effectively reduced CSC content, even as monotherapy. BMI1 inhibition with RU-A1 diminished the number of stem-like cells in vitro more efficiently than the model compound C-209, as demonstrated by clonogenic assays and impairment of CSC marker expression. Furthermore, xenograft assays in zebrafish showed that RU-A1 abrogated tumor growth in vivo.

Conclusions

This study demonstrates the ability to identify agents with the propensity for targeting CSCs in HCC that could be explored as novel treatments in the clinical setting.

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Lipid oxidation and antioxidants in food

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Cover Picture: Eur. J. Lipid Sci. Technol. 6∕2017

Encapsulation of cholecalciferol and ergocalciferol in oil-in-water emulsions by different homogenization techniques

Nauman Khalid, Isao Kobayashi, Marcos A. Neves, Kunihiko Uemura, Mitsutoshi Nakajima, and Hiroshi Nabetani

DOI: 10.1002/ejlt.201600247

Ergocalciferol and cholecalciferol are bioactive compounds whose deficiency in human system results in rickets, osteoporosis and osteomalacia. Different homogenization methods were used to formulate stable food-grade oil-in-water (O/W) emulsions encapsulating a mixture of ergocalciferol and cholecalciferol. The O/W emulsions formulated under appropriate homogenization conditions remained stable in terms of variation of their volume mean diameter over 30 days. Release profile of ergocalciferol and cholecalciferol encapsulated in the O/W emulsions was little affected by the homogenization methods used.

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Contents: Eur. J. Lipid Sci. Technol. 6∕2017

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Editorial Board: Eur. J. Lipid Sci. Technol. 6∕2017

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Back Cover: Eur. J. Lipid Sci. Technol. 6∕2017

Production of diacylglycerol-enriched oils by enzymatic interesterification and molecular distillation using soybean oil and distilled saturated monoacylglycerol

Qiong Chen, Ying Li, Junning Fu, Xiang Ma, Yinglai Teng, and Yong Wang

DOI: 10.1002/ejlt.201600332

Production of diacylglycerol-enriched oil as a novel ingredient for fluid margarine and monoacylglycerol with a certain unsaturation as a new emulsifier by enzymatic interesterification and molecular distillation.

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Pathologizing Altitude: Does Altitude Really Increase Sleep-Disordered Breathing?

High Altitude Medicine & Biology , Vol. 0, No. 0.


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How EMS providers can manage chronic stress

Over the past few years, there has been more awareness about PTSD and its effect on EMS providers

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Opioid-induced hyperalgesia in clinical anesthesia practice: what has remained from theoretical concepts and experimental studies?.

Purpose of review: This article reviews the phenomenon of opioid-induced hyperalgesia (OIH) and its implications for clinical anesthesia. The goal of this review is to give an update on perioperative prevention and treatment strategies, based on findings in preclinical and clinical research. Recent findings: Several systems have been suggested to be involved in the pathophysiology of OIH with a focus on the glutaminergic system. Very recently preclinical data revealed that peripheral [mu]-opioid receptors (MORs) are key players in the development of OIH and acute opioid tolerance (AOT). Peripheral MOR antagonists could, thus, become a new prevention/treatment option of OIH in the perioperative setting. Although the impact of OIH on postoperative pain seems to be moderate, recent evidence suggests that increased hyperalgesia following opioid treatment correlates with the risk of developing persistent pain after surgery. In clinical practice, distinction among OIH, AOT and acute opioid withdrawal remains difficult, especially because a specific quantitative sensory test to diagnose OIH has not been validated yet. Summary: Since the immediate postoperative period is not ideal to initiate long-term treatment for OIH, the best strategy is to prevent its occurrence. A multimodal approach, including choice of opioid, dose limitations and addition of nonopioid analgesics, is recommended. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Performance comparison of CareStart™ HRP2/pLDH combo rapid malaria test with light microscopy in north-western Tigray, Ethiopia: a cross-sectional study

Rapid diagnostic tests (RDTs) are alternative methods for microscopy in the diagnosis of malaria in resource limited settings. Among commercially available RDTs, CareStart™ Malaria test was found to show relia...

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Hospitalization for community-acquired febrile urinary tract infection: validation and impact assessment of a clinical prediction rule

There is a lack of severity assessment tools to identify adults presenting with febrile urinary tract infection (FUTI) at risk for complicated outcome and guide admission policy. We aimed to validate the Predi...

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Design of a syndemic based intervention to facilitate care for men who have sex with men with high risk behaviour: the syn.bas.in randomized controlled trial

Men who have sex with men (MSM) constitute a risk group for sexual transmitted infections (STIs), including HIV. Despite counselling interventions, risk behaviour remains high. Syndemic theory holds that psych...

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Primary Membranous Nephropathy

Membranous nephropathy (MN) is a unique glomerular lesion that is the most common cause of idiopathic nephrotic syndrome in nondiabetic white adults. About 80% of cases are renal limited (primary MN, PMN) and 20% are associated with other systemic diseases or exposures (secondary MN). This review focuses only on PMN. Most cases of PMN have circulating IgG4 autoantibody to the podocyte membrane antigen PLA2R (70%), biopsy evidence PLA2R staining indicating recent immunologic disease activity despite negative serum antibody levels (15%), or serum anti-THSD7A (3%–5%). The remaining 10% without demonstrable anti-PLA2R/THSd7A antibody or antigen likely have PMN probably secondary to a different, still unidentified, anti-podocyte antibody. Considerable clinical and experimental data now suggests these antibodies are pathogenic. Clinically, 80% of patients with PMN present with nephrotic syndrome and 20% with non-nephrotic proteinuria. Untreated, about one third undergo spontaneous remission, especially those with absent or low anti-PLA2R levels, one-third progress to ESRD over 10 years, and the remainder develop nonprogressive CKD. Proteinuria can persist for months after circulating anti-PLA2R/THSD7A antibody is no longer detectable (immunologic remission). All patients with PMN should be treated with supportive care from the time of diagnosis to minimize protein excretion. Patients with elevated anti-PLA2R/THSD7A levels and proteinuria >3.5 g/d at diagnosis, and those who fail to reduce proteinuria to <3.5 g after 6 months of supportive care or have complications of nephrotic syndrome, should be considered for immunosuppressive therapy. Accepted regimens include steroids/cyclophosphamide, calcineurin inhibitors, and B cell depletion. With proper management, only 10% or less will develop ESRD over the subsequent 10 years.

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Survival Benefit of Transplantation with a Deceased Diabetic Donor Kidney Compared with Remaining on the Waitlist

Background and objectives

Use of diabetic donor kidneys has been a necessary response to the donor organ shortage. Recipients of diabetic donor kidneys have higher mortality risk compared with recipients of nondiabetic donor kidneys. However, the survival benefit of transplantation with diabetic donor kidneys over remaining on the waitlist has not been previously evaluated.

Design, setting, participants, & measurements

We performed an observational cohort study of 437,619 kidney transplant candidates from the Organ Procurement and Transplantation Network database, including 8101 recipients of diabetic donor kidneys and 126,560 recipients of nondiabetic donor kidneys. We used time-varying Cox proportional hazards modeling to assess the mortality risk of accepting a diabetic donor kidney compared with remaining on the waitlist or receiving a nondiabetic donor kidney.

Results

Among transplant recipients, median follow-up was 8.9 years and mortality rate was 35 deaths per 1000 person-years. Recipients of diabetic donor kidneys had 9% lower mortality compared with remaining on the waitlist or transplantation with a nondiabetic donor kidney (adjusted hazard ratio, 0.91; 95% confidence interval, 0.84 to 0.98). Although recipients of nondiabetic donor kidneys with a Kidney Donor Profile Index score >85% had lower mortality risk (adjusted hazard ratio, 0.86; 95% confidence interval, 0.81 to 0.91), recipients of diabetic donor kidneys with an index score >85% did not show any difference (adjusted hazard ratio, 1.09; 95% confidence interval, 0.97 to 1.22). Patients aged <40 years attained no survival benefit from transplantation with diabetic donor kidneys; diabetic patients at centers with long waitlist times attained the greatest survival benefit.

Conclusions

Diabetic donor kidneys appear associated with higher mortality risk compared with nondiabetic donor kidneys, but offer greater survival benefit compared with remaining on the waitlist for many candidates. Patients with high risk of mortality on the waitlist at centers with long wait times appear to benefit most from transplantation with diabetic donor kidneys.

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Kidney Outcomes and Risk Factors for Nephritis (Flare/De Novo) in a Multiethnic Cohort of Pregnant Patients with Lupus

Background and objectives

Kidney disease is a critical concern in counseling patients with lupus considering pregnancy. This study sought to assess the risk of renal flares during pregnancy in women with previous lupus nephritis in partial or complete remission, particularly in those with antidouble-stranded DNA antibodies and low complement levels, and the risk of new-onset nephritis in patients with stable/mildly active SLE.

Design, setting, participants, & measurements

We assessed active nephritis (renal flares and de novo kidney disease) and associated predictors during pregnancy in patients with lupus with urine protein ≤1000 mg and serum creatinine <1.2 mg/dl at baseline; 373 patients (52% ethnic/racial minorities) enrolled between 2003 and 2012 were prospectively followed in the Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Syndrome and Systemic Lupus Erythematosus Study. Active nephritis was defined by proteinuria increase of >500 mg and/or red blood cell casts.

Results

Of 118 patients with previous kidney disease, 13 renal flares (11%) occurred (seven of 89 in complete remission and six of 29 in partial remission) compared with four with de novo kidney involvement (2%) in 255 patients without past kidney disease (P<0.001). Active nephritis was not associated with ethnicity, race, age, creatinine, BP, or antihypertensive and other medications. In multivariable logistic regression analyses, patients with past kidney disease in complete or partial remission more often experienced active nephritis (adjusted odds ratio, 6.88; 95% confidence interval, 1.84 to 25.71; P=0.004 and adjusted odds ratio, 20.98; 95% confidence interval, 4.69 to 93.98; P<0.001, respectively) than those without past kidney disease. Low C4 was associated with renal flares/de novo disease (adjusted odds ratio, 5.59; 95% confidence interval, 1.64 to 19.13; P<0.01) but not low C3 or positive anti-dsDNA alone.

Conclusions

De novo kidney involvement in SLE, even in ethnic/racial minorities, is uncommon during pregnancy. Past kidney disease and low C4 at baseline independently associate with higher risk of developing active nephritis. Antibodies to dsDNA alone should not raise concern, even in patients with past kidney disease, if in remission.

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Examining the Association between Hemodialysis Access Type and Mortality: The Role of Access Complications

Background and objectives

People receiving hemodialysis to treat kidney failure need a vascular access (a fistula, a graft, or a central venous catheter) to connect to the blood purification machine. Higher rates of access complications are considered the mechanism responsible for the excess mortality observed among catheter or graft users versus fistula users. We tested this hypothesis using mediation analysis.

Design, setting, participants, & measurements

We studied incident patients who started hemodialysis therapy from North America, Europe, and Australasia (the Dialysis Outcomes and Practice Patterns Study; 1996–2011). We evaluated the association between access type and time to noninfectious (e.g., thrombosis) and infectious complications of the access (mediator model) and the relationship between access type and time-dependent access complications with 6-month mortality from the creation of the first permanent access (outcome model). In mediation analysis, we formally tested whether access complications explain the association between access type and mortality.

Results

Of the 6119 adults that we studied (mean age =64 [SD=15] years old; 58% men; 47% patients with diabetes), 50% had a permanent catheter for vascular access, 37% had a fistula, and 13% had a graft. During the 6-month study follow-up, 2084 participants (34%) developed a noninfectious complication of the access, 542 (8.9%) developed an infectious complication, and 526 (8.6%) died. Access type predicted the occurrence of access complications; both access type and complications predicted mortality. The associations between access type and mortality were nearly identical in models excluding and including access complications (hazard ratio, 2.00; 95% confidence interval, 1.55 to 2.58 versus hazard ratio, 2.01; 95% confidence interval, 1.56 to 2.59 for catheter versus fistula, respectively). In mediation analysis, higher mortality with catheters or grafts versus fistulas was not the result of increased rates of access complications.

Conclusions

Hemodialysis access complications do not seem to explain the association between access type and mortality. Clinical trials are needed to clarify whether these associations are causal or reflect confounding by underlying disease severity.

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Reassessing Recommendations for Choice of Vascular Access

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Statistical Methods for Cohort Studies of CKD: Prediction Modeling

Prediction models are often developed in and applied to CKD populations. These models can be used to inform patients and clinicians about the potential risks of disease development or progression. With increasing availability of large datasets from CKD cohorts, there is opportunity to develop better prediction models that will lead to more informed treatment decisions. It is important that prediction modeling be done using appropriate statistical methods to achieve the highest accuracy, while avoiding overfitting and poor calibration. In this paper, we review prediction modeling methods in general from model building to assessing model performance as well as the application to new patient populations. Throughout, the methods are illustrated using data from the Chronic Renal Insufficiency Cohort Study.

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Time to Improve Informed Consent for Dialysis: An International Perspective

The literature reveals that current nephrology practice in obtaining informed consent for dialysis falls short of ethical and legal requirements. Meeting these requirements represents a significant challenge, especially because the benefits and risks of dialysis have shifted significantly with the growing number of older, comorbid patients. The importance of informed consent for dialysis is heightened by several concerns, including: (1) the proportion of predialysis patients and patients on dialysis who lack capacity in decision making and (2) whether older, comorbid, and frail patients understand their poor prognosis and the full implications to their independence and functional status of being on dialysis. This article outlines the ethical and legal requirements for a valid informed consent to dialysis: (1) the patient was competent, (2) the consent was made voluntarily, and (3) the patient was given sufficient information in an understandable manner to make the decision. It then considers the application of these requirements to practice across different countries. In the process of informed consent, the law requires a discussion by the physician of the material risks associated with dialysis and alternative options. We argue that, legally and ethically, this discussion should include both the anticipated trajectory of the illness and the effect on the life of the patient with particular regard to the outcomes most important to the individual. In addition, a discussion should occur about the option of a conservative, nondialysis pathway. These requirements ensure that the ethical principle of respect for patient autonomy is honored in the context of dialysis. Nephrologists need to be open to, comfortable with, and skillful in communicating this information. From these clear, open, ethically, and legally valid consent discussions, a significant dividend will hopefully flow for patients, families, and nephrologists alike.

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Could MRI Be Used To Image Kidney Fibrosis? A Review of Recent Advances and Remaining Barriers

A key contributor to the progression of nearly all forms of CKD is fibrosis, a largely irreversible process that drives further kidney injury. Despite its importance, clinicians currently have no means of noninvasively assessing renal scar, and thus have historically relied on percutaneous renal biopsy to assess fibrotic burden. Although helpful in the initial diagnostic assessment, renal biopsy remains an imperfect test for fibrosis measurement, limited not only by its invasiveness, but also, because of the small amounts of tissue analyzed, its susceptibility to sampling bias. These concerns have limited not only the prognostic utility of biopsy analysis and its ability to guide therapeutic decisions, but also the clinical translation of experimental antifibrotic agents. Recent advances in imaging technology have raised the exciting possibility of magnetic resonance imaging (MRI)–based renal scar analysis, by capitalizing on the differing physical features of fibrotic and nonfibrotic tissue. In this review, we describe two key fibrosis-induced pathologic changes (capillary loss and kidney stiffening) that can be imaged by MRI techniques, and the potential for these new MRI-based technologies to noninvasively image renal scar.

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Diarrhea in a Long-Term Kidney-Pancreas Recipient

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Two phosphAte taRGets in End-stage renal disease Trial (TARGET): A Randomized Controlled Trial

Background and objectives

Hyperphosphatemia is common among recipients of maintenance dialysis and is associated with a higher risk of mortality and cardiovascular events. A large randomized trial is needed to determine whether lowering phosphate concentrations with binders improves patient-important outcomes. To inform such an effort we conducted a pilot randomized controlled trial.

Design, setting, participants, & measurements

We conducted a randomized controlled trial of prevalent hemodialysis recipients already receiving calcium carbonate as a phosphate binder at five Canadian centers between March 31, 2014 and October 2, 2014. Participants were randomly allocated to 26 weeks of an intensive phosphate goal of 2.33–4.66 mg/dl (0.75–1.50 mmol/L) or a liberalized target of 6.20–7.75 mg/dl (2.00–2.50 mmol/L) by titrating calcium carbonate using a dosing nomogram. The primary outcome was the difference in the change in serum phosphate from randomization to 26 weeks.

Results

Fifty-three participants were randomized to the intensive group and 51 to the liberalized group. The median (interquartile range) daily dose of elemental calcium at 26 weeks was 1800 (1275–3000) mg in the intensive group, and 0 (0–500) mg in the liberalized group. The mean (SD) serum phosphate at 26 weeks was 4.53 (1.12) mg/dl (1.46 [0.36] mmol/L) in the intensive group and 6.05 (1.40) mg/dl (1.95 [0.45] mmol/L) in the liberalized group. Phosphate concentration in the intensive group declined by 1.24 (95% confidence interval, 0.75 to 1.74) mg/dl (0.40 [95% confidence interval, 0.24 to 0.56] mmol/L) compared with the liberalized group. There were no statistically significant differences between the two groups in the risk of hypercalcemia, hypocalcemia, parathyroidectomy, or major vascular events.

Conclusions

It is feasible to achieve and maintain a difference in serum phosphate concentrations in hemodialysis recipients by titrating calcium carbonate. A large trial is needed to determine if targeting a lower serum phosphate concentration improves patient-important outcomes.

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Albuminuria, Proteinuria, and Renal Disease Progression in Children with CKD

Background and objectives

The role of albuminuria as an indicator of progression has not been investigated in children with CKD in the absence of diabetes.

Design, setting, participants, & measurements

Children were enrolled from 49 centers of the CKD in Children study between January of 2005 and March of 2014. Cross-sectional multivariable linear regression (n=647) was used to examine the relationship between urine protein-to-creatinine (UP/C [milligrams per milligram]) and albumin-to-creatinine (ACR [milligrams per gram]) with eGFR (milliliters per minute per 1.73 m²). Parametric time-to-event analysis (n=751) was used to assess the association of UP/C, ACR, and urine nonalbumin-to-creatinine (Unon-alb/cr [milligrams per gram]) on the time to the composite endpoint of initiation of RRT or 50% decline in eGFR.

Results

The median follow-up time was 3.4 years and 202 individuals experienced the event. Participants with a UP/C≥0.2 mg/mg and ACR≥30 mg/g had a mean eGFR that was 16 ml/min per 1.73 m² lower than those with a UP/C<0.2 mg/mg and ACR<30 mg/g. Individuals with ACR<30 mg/g, but a UP/C≥0.2 mg/mg, had a mean eGFR that was 9.3 ml/min per 1.73 m² lower than those with a UP/C<0.2 mg/mg and ACR<30 mg/g. When categories of ACR and Unon-alb/cr were created on the basis of clinically meaningful cutoff values of UP/C with the same sample sizes for comparison, the relative times (RTs) to the composite end-point were almost identical when comparing the middle (RT=0.31 for UP/C [0.2–2.0 mg/mg], RT=0.38 for ACR [56–1333 mg/g], RT=0.31 for Unon-alb/cr [118–715 mg/g]) and the highest (RT=0.08 for UP/C [>2.0 mg/mg], RT=0.09 for ACR [>1333 mg/g], RT=0.07 for Unon-alb/cr [>715 mg/g]) levels to the lowest levels. A similar trend was seen when categories were created on the basis of clinically meaningful cutoff values of ACR (<30, 30–300, >300 mg/g).

Conclusions

In children with CKD without diabetes, the utility of an initial UP/C, ACR, and Unon-alb/cr for characterizing progression is similar.

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Choice of Hemodialysis Access in Older Adults: A Cost-Effectiveness Analysis

Background and objectives

Although arteriovenous fistulas have been found to be the most cost-effective form of hemodialysis access, the relative benefits of placing an arteriovenous fistula versus an arteriovenous graft seem to be least certain for older adults and when placed preemptively. However, older adults' life expectancy is heterogeneous, and most patients do not undergo permanent access creation until after dialysis initiation. We evaluated cost-effectiveness of arteriovenous fistula placement after dialysis initiation in older adults as a function of age and life expectancy.

Design, setting, participants, & measurements

Using a hypothetical cohort of patients on incident hemodialysis with central venous catheters, we constructed Markov models of three treatment options: (1) arteriovenous fistula placement, (2) arteriovenous graft placement, or (3) continued catheter use. Costs, utilities, and transitional probabilities were derived from existing literature. Probabilistic sensitivity analyses were performed by age group (65–69, 70–74, 75–79, 80–84, and 85–89 years old) and quartile of life expectancy. Costs, quality-adjusted life-months, and incremental cost-effectiveness ratios were evaluated for up to 5 years.

Results

The arteriovenous fistula option was cost effective compared with continued catheter use for all age and life expectancy groups, except for 85–89 year olds in the lowest life expectancy quartile. The arteriovenous fistula option was more cost effective than the arteriovenous graft option for all quartiles of life expectancy among the 65- to 69-year-old age group. For older age groups, differences in cost-effectiveness between the strategies were attenuated, and the arteriovenous fistula option tended to only be cost effective in patients with life expectancy >2 years. For groups for which the arteriovenous fistula option was not cost saving, the cost to gain one quality-adjusted life-month ranged from $2294 to $14,042.

Conclusions

Among older adults, the cost-effectiveness of an arteriovenous fistula placed within the first month of dialysis diminishes with increasing age and lower life expectancy and is not the most cost-effective option for those with the most limited life expectancy.

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Sleep and CKD in Chinese Adults: A Cross-Sectional Study

Background and objectives

To assess the association between self-reported sleep duration and quality and odds of having CKD in Chinese adults on the basis of a community study.

Design, setting, participants, & measurements

In this cross-sectional study, we included 11,040 Chinese adults who participated in an ongoing prospective study, the Kailuan cohort. Survey questionnaire items addressed insomnia, daytime sleepiness, snoring, and sleep duration during their 2012 interview. Overall sleep quality was evaluated by summarizing these four sleep parameters. Fasting blood samples and single random midstream morning urine samples were collected in 2012 and analyzed for serum creatinine and proteinuria. CKD was defined by eGFR<60 ml/min per 1.73 m² or proteinuria >300 mg/dl. We also examined those at high or very high risk of having CKD, on the basis of the Kidney Disease Improving Global Outcomes recommendations. The association between sleep quality and CKD was assessed using logistic regression model.

Results

Worse overall sleep quality was associated with higher likelihood of being high or very high risk for CKD (multiadjusted odds ratio, 2.69; 95% confidence interval, 1.30 to 5.59 comparing two extreme categories; P trend <0.01), but not overall CKD (multiadjusted odds ratio, 1.58; 95% confidence interval, 0.89 to 2.80 comparing two extreme categories; P trend =0.46), after adjusting for potential confounders. Specifically, individuals with worse sleep quality were more likely to have proteinuria (multiadjusted odds ratio, 1.95; 95% confidence interval, 1.03 to 3.67 comparing two extreme categories; P trend =0.02), rather than lower eGFR level (multiadjusted mean eGFR levels were 96.4 and 93.6 ml/min per 1.73 m² in the two extreme sleep categories, respectively; P trend =0.13). However, there was no statistically significant association between individual sleep parameters and CKD status.

Conclusions

Worse overall sleep quality was associated with higher odds of being high or very high risk for CKD and proteinuria in Chinese adults.

http://ift.tt/2sdDBFN