Comparative analysis of azacitidine and intensive chemotherapy as front-line treatment of elderly patients with acute myeloid leukemia

Abstract

The present observational study aimed to compare the efficacy of azacitidine (AZA) and intensive chemotherapy (IC) in elderly patients with untreated acute myeloid leukemia (AML), diagnosed according to WHO criteria. In the two groups, we evaluated complete remission (CR), overall survival (OS), and disease-free survival (DFS). The AZA group included 89 patients; median age was 73 years (range 61–80) and median white blood cell count (WBCc) 2.5 × 10⁹/L (range 0.27–83), 45% of the patients had BM blasts ≥ 30%, and 44 (49%) had a secondary AML (sAML). Karyotype was evaluable in 69 patients: 51 (74%) had intermediate-risk abnormalities and 18 (26%) an unfavorable risk karyotype. IC group consisted of 110 patients who received an induction course with mitoxantrone, cytarabine, and etoposide, followed by two consolidation cycles including idarubicin, cytarabine, and etoposide. Median age was 67 years (range 61–78) and median WBCc 8.0 × 10⁹/L (range 0.69–258); 44 (40%) had a sAML. Karyotype was evaluable in 88 patients, 71 (81%) had intermediate risk, and 17 (19%) unfavorable risk karyotype. To minimize the effects of treatment selection bias, adjustments were made using the propensity-score matching method, which yielded 74 patient pairs. CR rate was significantly higher in IC vs AZA group (73 vs 25%, respectively) (p < 0.0001), but the 3-year OS rates and median OS were not significantly different (21.6 vs 11% and 15.8 vs 13 months, respectively). Our analysis suggests similar outcomes with AZA compared to IC. Controlled, randomized clinical trials are warranted to confirm this conclusion.

https://ift.tt/2LAxxgu

Harnessing immune history to combat influenza viruses

Jenna J Guthmiller | Patrick C Wilson

https://ift.tt/2JvMYpu

Correction to: Various Shapes of Cultural Biosemiotics

In the original published article, in discussing Paul Cobley's work, I made an unclear statement and one that was actually false. I mentioned that Cobley is critical of "otherness" as it has been explored in sex and gender studies.

https://ift.tt/2JpJmcI

Infectious disease burden and antibiotic prescribing in primary care in Israel

Antibiotics are frequently prescribed at many of the visits to primary care clinics, often for conditions for which they provide no benefit, including viral respiratory tract infections.

https://ift.tt/2MfVcUm

Time to epileptiform activity and EEG background recovery are independent predictors after cardiac arrest

Electroencephalography (EEG) is the most common tool used to support the clinical neurological examination when assessing prognosis in comatose patients resuscitated after cardiac arrest (CA)(Friberg et al., 2015). Continuous EEG-monitoring (cEEG) is increasingly used and recommended after CA(Claassen et al., 2013, Callaway et al., 2015) to detect electrographic seizure activity and may add important information about the temporal dynamics of brain function recovery or deterioration.

https://ift.tt/2Jp4kbI

Clinicopathological, Immunohistochemical and molecular correlation of neural crest transcription factor SOX10 expression in triple negative breast carcinoma

The transcription factor SOX10 mediates the differentiation of neural crest–derived cells, and SOX10 by immunohistochemistry(IHC) is used primarily for the diagnosis of melanoma. SOX10 expression has been previously documented in benign breast myoepithelial cells. However there is limited literature on its expression in triple negative breast carcinoma(TNBC). The aim was to study the clinical, pathologic and molecular profiles of SOX10+ tumors in TNBC. Tissue microarrays of TNBC were evaluated for SOX10 expression in 48cases.

https://ift.tt/2sVfbyX

Cold adaptation and replicable microbial community development during long-term low-temperature anaerobic digestion treatment of synthetic sewage

ABSTRACT

The development and activity of a cold-adapting microbial community was monitored during low-temperature anaerobic digestion (LtAD) treatment of wastewater. Two replicate hybrid anaerobic sludge bed-fixed-film reactors treated a synthetic sewage wastewater at 12°C, at organic loading rates of 0.25–1.0 kg chemical oxygen demand (COD) m⁻³ d⁻¹, over 889 days. The inoculum was obtained from a full-scale anaerobic digestion reactor, which was operated at 37°C. Both LtAD reactors readily degraded the influent with COD removal efficiencies regularly exceeding 78% for both the total and soluble COD fractions. The biomass from both reactors was sampled temporally and tested for activity against hydrolytic and methanogenic substrates at 12°C and 37°C. Data indicated that significantly enhanced low-temperature hydrolytic and methanogenic activity developed in both systems. For example, the hydrolysis rate constant (k) at 12°C had increased 20–30-fold by comparison to the inoculum by day 500. Substrate affinity also increased for hydrolytic substrates at low temperature. Next generation sequencing demonstrated that a shift in a community structure occurred over the trial, involving a 1-log-fold change in 25 SEQS (OTU-free approach) from the inoculum. Microbial community structure changes and process performance were replicable in the LtAD reactors.

https://ift.tt/2HAfOmT

A microbial endocrinology-based simulated small intestinal medium for the evaluation of neurochemical production by gut microbiota

ABSTRACT

Microbial endocrinology represents the union of microbiology and neurobiology and is concerned with the ability of neurochemicals to serve as an evolutionary-based language between host and microbiota in health and disease. The recognition that microorganisms produce, modify and respond to the same neurochemicals utilized in the various signaling pathways of their mammalian hosts is increasingly being recognized as a mechanism by which the host and microbiota may interact to influence the progression of infectious disease as well as influence behavior through the microbiota-gut-brain axis. While the capacity for bacteria to produce neurochemicals has been recognized for decades, the degree to which this occurs in the environment of the gastrointestinal tract is still poorly understood. By combining techniques used in analytic chemistry, food science and environmental microbiology, a novel culture-based method was developed which generates a medium utilizing animal feed which resembles the contents of the small intestine. The usage of this medium allows for the in vitro growth of bacteria native to the gastrointestinal tract in an environment that is reflective of the small-intestinal host-based milieu. We describe a detailed protocol for the preparation of this medium and the quantification of neurochemicals by microorganisms grown therein. Catecholamines including dopamine and its precursor L-3,4-dihydroxyphenalanine (L-DOPA) as well as biogenic amines including tyramine and its precursor tyrosine, serve as prototypical examples of neurochemicals that are quantifiable with the methods described herein.

https://ift.tt/2sMcD6Y

Relationship between dissolved organic matter quality and microbial community composition across polar glacial environments

ABSTRACT

Vast expanses of Earth's surface are covered by ice, with microorganisms in these systems affecting local and global biogeochemical cycles. We examined microbial assemblages from habitats fed by glacial meltwater within the McMurdo Dry Valleys, Antarctica and on the west Greenland Ice Sheet (GrIS), evaluating potential physicochemical factors explaining trends in community structure. Microbial assemblages present in the different Antarctic dry valley habitats were dominated by Sphingobacteria andFlavobacteria, while Gammaproteobacteria and Sphingobacteria prevailed in west GrIS supraglacial environments. Microbial assemblages clustered by location (Canada Glacier, Cotton Glacier and west GrIS) and were separated by habitat type (i.e. ice, cryoconite holes, supraglacial lakes, sediment and stream water). Community dissimilarities were strongly correlated with dissolved organic matter (DOM) quality. Microbial meltwater assemblages were most closely associated with different protein-like components of the DOM pool. Microbes in environments with mineral particles (i.e. stream sediments and cryoconite holes) were linked to DOM containing more humic-like fluorescence. Our results demonstrate the establishment of distinct microbial communities within ephemeral glacial meltwater habitats, with DOM-microbe interactions playing an integral role in shaping communities on local and polar spatial scales.

https://ift.tt/2HAfEfh

Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis

Here, we present a protocol to confirm the presence of point mutation for the diagnosis of hereditary transthyretin amyloidosis, using Ala97Ser, the most common endemic mutation in Taiwan, as an example.

https://ift.tt/2JoRdqV

A Protocol to Acquire the Degenerative Tenocyte from Humans

In vitro use of degenerative tenocytes is essential when investigating the efficacy of novel treatment on tendinopathy. However, most research studies use only the animal model or a healthy tenocyte. We propose the following protocol to isolate human degenerative tenocytes during surgery.

https://ift.tt/2LDh5vU

Effects of post-fracture non-weight-bearing immobilization on muscle atrophy, intramuscular and intermuscular adipose tissues in the thigh and calf

Abstract

Objective

Disuse and/or a non-weight-bearing condition changes muscle composition, with decreased skeletal muscle tissue and increased fat within (intramuscular adipose tissue, IntraMAT) and between (intermuscular adipose tissue, InterMAT) given muscles. Excessive adipose tissue contributes to dysfunctional and metabolically impaired muscle. How these adipose tissues change during orthopedic treatment (e.g., cast immobilization, daily use of crutches) is not well documented. This study aimed to quantify changes in IntraMAT, InterMAT, and thigh and calf muscle tissue during orthopedic treatment.

Materials and methods

We studied 8 patients with fifth metatarsal bone or fibular fractures. The ankle joint involved underwent plaster casting for approximately 4 weeks, with crutches used during that time. Axial T1-weighted MRI at the mid-thigh and a 30% proximal site at the calf were obtained to measure IntraMAT and InterMAT cross-sectional areas (CSAs) and skeletal muscle tissue CSA before treatment and 4 weeks afterward.

Results

Thigh and calf muscle tissue CSAs were significantly decreased from before to after treatment: thigh, 85.8 ± 7.6 to 77.1 ± 7.3 cm²; calf, 53.3 ± 5.5 to 48.9 ± 5.0 cm² (p < 0.05). None of the IntraMAT or InterMAT changes was statistically significant. There was a relation between the percentage change of thigh IntraMAT CSA and muscle tissue CSA (r_s = −0.86, p < 0.01).

Conclusions

The 4 weeks of treatment primarily induced skeletal muscle atrophy with less of an effect on IntraMAT or InterMAT. There is a risk of increasing IntraMAT relatively by decreasing skeletal muscle tissue size during orthopedic treatment.

https://ift.tt/2JyuXXL

CRISPR-mediated Loss of Function Analysis in Cerebellar Granule Cells Using In Utero Electroporation-based Gene Transfer

Conventional loss-of-function studies of genes using knockout animals have often been costly and time-consuming. Electroporation-based CRISPR-mediated somatic mutagenesis is a powerful tool to understand gene functions in vivo. Here, we report a method to analyze knockout phenotypes in proliferating cells of the cerebellum.

https://ift.tt/2y4fz4e

Whole-brain Segmentation and Change-point Analysis of Anatomical Brain MRI—Application in Premanifest Huntington's Disease

This paper describes a statistical model for volumetric MRI data analysis, which identifies the "change-point" when brain atrophy begins in premanifest Huntington's disease. Whole-brain mapping of the change-points is achieved based on brain volumes obtained using an atlas-based segmentation pipeline of T1-weighted images.

https://ift.tt/2JyhD5H

Obtaining 3D Chemical Maps by Energy Filtered Transmission Electron Microscopy Tomography

This paper describes a protocol to achieve 3D chemical maps combining energy filtered imaging and electron tomography. The chemical distribution of two catalyst supports formed by elements that are difficult to distinguish by other imaging techniques was studied. Each application consists of mapping overlapped chemical elements - respectively spaced-ionization edges.

https://ift.tt/2MbbfTy

Alpha-synuclein delays mitophagy and targeting Miro rescues neuron loss in Parkinson’s models

Abstract

Alpha-synuclein is a component of Lewy bodies, the pathological hallmark of Parkinson's disease (PD), and is also mutated in familial PD. Here, by extensively analyzing PD patient brains and neurons, and fly models, we show that alpha-synuclein accumulation results in upregulation of Miro protein levels. Miro is a motor/adaptor on the outer mitochondrial membrane that mediates mitochondrial motility, and is removed from damaged mitochondria to facilitate mitochondrial clearance via mitophagy. PD patient neurons abnormally accumulate Miro on the mitochondrial surface leading to delayed mitophagy. Partial reduction of Miro rescues mitophagy phenotypes and neurodegeneration in human neurons and flies. Upregulation of Miro by alpha-synuclein requires an interaction via the N-terminus of alpha-synuclein. Our results highlight the importance of mitochondria-associated alpha-synuclein in human disease, and present Miro as a novel therapeutic target.

https://ift.tt/2sIg4eY

Workplace violence, job satisfaction, burnout, perceived organisational support and their effects on turnover intention among Chinese nurses in tertiary hospitals: a cross-sectional study

Objectives

Our aims were to assess the relationship between workplace violence, job satisfaction, burnout, organisational support and turnover intention, and to explore factors associated with turnover intention among nurses in Chinese tertiary hospitals.

Methods

The purposive sampling method was used to collect data from August 2016 through January 2017. A total of 1761 nurses from 9 public tertiary hospitals in 4 provinces (municipalities) located in eastern (Beijing), central (Heilongjiang, Anhui) and western (Shaanxi) regions of China completed the questionnaires (effective response rate=85.20%). A cross-sectional study was conducted using the Workplace Violence Scale, Chinese Maslach Burnout Inventory General Survey, Minnesota Job Satisfaction Questionnaire Revised Short Version, Perceived Organizational Support-Simplified Version Scale and Turnover Intention Scale.

Results

A total of 1216 of 1706 (69.1%) participants had high turnover intention. During the previous 12 months, the prevalence of physical violence and psychological violence towards nurses was 9.60% and 59.64%, respectively. As expected, the level of turnover intention was negatively correlated with participants' scores on job satisfaction (r=–0.367, p<0.001) and perceived organisational support (r=–0.379, p<0.001), respectively. Burnout was positively associated with turnover intention (r=0.444, p<0.001). Workplace violence was positively associated with turnover intention (β=0.035, p<0.001) in linear regression analysis. The total effect (β=0.53) of workplace violence on turnover intention comprised its direct effect (β=0.36) and its indirect effect (β=0.17).

Conclusions

Perceived organisational support served as a mediator between workplace violence, job satisfaction, burnout and turnover intention, and it had a significantly negative impact on turnover intention. Therefore, nursing managers should understand the importance of the organisation's support and establish a reasonable incentive system to decrease turnover intention.

https://ift.tt/2Jok6DD

Who attends out-of-hours general practice appointments? Analysis of a patient cohort accessing new out-of-hours units

Objectives

This report describes the patients who used additional out-of-hours (OOH) appointments offered through a UK scheme intended to increase patient access to primary care by extending OOH provision.

Design

Cohort study and survey data.

Setting

OOH appointments offered in four units in one region in England (October 2015 to November 2016).

Methods

Unidentifiable data on all patients were abstracted from a bespoke appointment system and the responses to a patient opinion questionnaire about this service. Descriptive analysis of the appointment data was conducted. Multivariate analysis of the opinion survey data examined the characteristics of the patients who would have gone to the emergency department (ED) had the OOH appointments not been available.

Results

There were 24 448 appointments for 19 701 different patients resulting in 29 629 service outcomes. Women dominated the uptake and patients from the poorest fifth of the population used nearly 40% of appointments. The patient survey found OOH appointments were extremely popular—93% selecting 'extremely likely' or 'likely' to recommend the service. Multivariate analysis of patient opinion survey data on whether ED would have been an alternative to the OOH service found that men, young children, people of Asian heritage and the most deprived were more likely to have gone to ED without this service.

Conclusions

The users of the OOH service were substantially different from in-hours service users with a large proportion of children under age 5, and the poor, which support the idea that there may be unmet need as the poor have the least flexible working conditions. These results demonstrate the need for equality impact assessment in planning service improvements associated with policy implementation. It suggests that OOH need to take account of patients expectations about convenience of appointments and how patients use services for urgent care needs.

https://ift.tt/2JnDnoF

Ultrasound-guided versus landmark approach for peripheral intravenous access by critical care nurses: a randomised controlled study

Objective

Establishing a peripheral intravenous catheter (PIVC) after a long intensive care unit (ICU) stay can be a challenge for nurses, as these patients may present vascular access issues. The aim of this study was to compare an ultrasound-guided method (UGM) versus the landmark method (LM) for the placement of a PIVC in ICU patients who no longer require a central intravenous catheter (CIVC).

Design

Randomised, controlled, prospective, open-label, single-centre study.

Setting

Tertiary teaching hospital.

Participants

114 awake patients hospitalised in ICU fulfilling the following criteria: (1) with a central venous catheter that was no longer required, (2) needing a PIVC to replace the central venous catheter and (3) with no apparent or palpable veins on upper limbs after tourniquet placement.

Intervention

Placement of a PIVC using an UGM.

Primary outcome

Number of attempts for the establishment of a PIVC in the upper limbs.

Results

57 patients were respectively included in both the UGM group and LM group. Stasis oedema in the upper limbs was the main cause of poor venous access identified in 80% of patients. Both the number of attempts (2 (1–4), p=0.911) and catheter lifespan ((3 (1–3) days and 3 (2–3) days, p=0.719) were similar between the two groups. Catheters in the UGM group tended to be larger (p=0.059) and be associated with increased extravasation (p=0.094).

Conclusion

In ICU patients who no longer require a CIVC, use of an UGM for the establishment of a PIVC is not associated with a reduction in the number of attempts compared with LM.

Trial registration number

NCT02285712; Results.

https://ift.tt/2LzKI1i

Shared decision-making for people living with dementia in extended care settings: a systematic review

Background

Shared decision-making is recognised as an important element of person-centred dementia care.

Objectives

The aim of this review was to explore how people living with dementia and cognitive impairment can be included in day-to-day decisions about their health and care in extended care settings.

Design

A systematic review including primary research relating to shared decision-making, with cognitively impaired adults in (or transferrable to) extended care settings. Databases searched were: CINAHL, PubMed, the Cochrane Library, NICE Evidence, OpenGrey, Autism Data, Google Scholar, Scopus and Medicines Complete (June to October 2016 and updated 2018) for studies published in the last 20 years.

Results

Of the 19 included studies 15 involved people with living dementia, seven in extended care settings. People living with cognitive impairment often have the desire and ability to participate in decision-making about their everyday care, although this is regularly underestimated by their staff and family care partners. Shared decision-making has the potential to improve quality of life for both the person living with dementia and those who support them. How resources to support shared decision-making are implemented in extended care settings is less well understood.

Conclusions

Evidence suggests that people living with cognitive impairment value opportunities to be involved in everyday decision-making about their care. How these opportunities are created, understood, supported and sustained in extended care settings remains to be determined.

Trial registration number

CRD42016035919

https://ift.tt/2JnDdxz

Which patients receive surgery in for-profit and non-profit hospitals in a universal health system? An explorative register-based study in Norway

Objectives

To compare the socioeconomic status (SES) and case-mix among day surgical patients treated at private for-profit hospitals (PFPs) and non-profit hospitals (NPs) in Norway, and to explore whether the use of PFPs in a universal health system has compromised the principle of equal access regardless of SES.

Design

A retrospective, exploratory study comparing hospital types using the Norwegian Patient Register linked with socioeconomic data from Statistics Norway by using Norwegian citizens' personal identification numbers.

Setting

The Norwegian healthcare system.

Population

All publicly financed patients in five Norwegian metropolitan areas having day surgery for meniscus (34 100 patients), carpal tunnel syndrome (15 010), benign breast hypertrophy (6297) or hallux valgus (2135) from 2009 to 2014.

Primary outcome measure

Having surgery at a PFP or NP.

Results

Across four unique procedures, the adjusted odds ratios (aORs) for using PFPs were generally lower for the lowest educational level (0.77–0.87) and the lowest income level (0.68–0.89), though aORs were not always significant. Likewise, comorbidity and previous hospitalisation had lower aORs (0.62–0.95; 0.44–0.97, respectively) for having surgery at PFPs across procedures, though again aORs were not always significant. No clear patterns emerged with respect to age, gender or higher levels of income and education.

Conclusions

The evidence from our study of four procedures suggests that equal access to PFPs compared with NPs for those patients at the lowest education and income levels may be compromised, though further investigations are needed to generalise these findings across more procedures and probe causal mechanisms and appropriate policy remedies. The finding that comorbidity and previous hospitalisation had lower odds of treatment at PFPs indicates that NPs play an essential role for more complex patients, but raises questions about patient preference and cream skimming.

https://ift.tt/2Hxo7Qh

Effect of 6 months of hybrid closed-loop insulin delivery in adults with type 1 diabetes: a randomised controlled trial protocol

Introduction

Manual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective of the present study is to determine the effectiveness of 6 months' closed-loop compared with manually determined insulin dosing on time-in-target glucose range in adults with type 1 diabetes.

Methods and analysis

This open-label, seven-centre, randomised controlled parallel group clinical trial will compare home-based hybrid closed-loop versus standard diabetes therapy in Australia. Adults aged ≥25 years with type 1 diabetes using intensive insulin therapy (via multiple daily injections or insulin pump, total enrolment target n=120) will undertake a run-in period including diabetes and carbohydrate-counting education, clinical optimisation and baseline data collection. Participants will then be randomised 1:1 either to 26 weeks of MiniMed 670G hybrid closed-loop system therapy (Medtronic, Northridge, CA, USA) or continuation of their current diabetes therapy. The hybrid closed-loop system delivers insulin automatically to address basal requirements and correct to target glucose level, while bolus doses for meals require user initiation and carbohydrate estimation. Analysis will be intention to treat, with the primary outcome time in continuous glucose monitoring (CGM) target range (3.9–10.0 mmol/L) during the final 3 weeks of intervention. Secondary outcomes include: other CGM parameters, HbA_1c, severe hypoglycaemia, psychosocial well-being, sleep, cognition, electrocardiography, costs, quality of life, biomarkers of vascular health and hybrid closed-loop system performance. Semistructured interviews will assess the expectations and experiences of a subgroup of hybrid closed-loop users.

Ethics and dissemination

The study has Human Research Ethics Committee approval. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results will be disseminated at scientific conferences and via peer-reviewed publications.

Trial registration number

ACTRN12617000520336; Pre-results.

https://ift.tt/2HyvyXm

Work-related injuries resulting in death in Chile: a cross-sectional study on 2014 and 2015 registries

Objective

To characterise work-related fatal events that occurred in Chile in 2014 and 2015 in workers covered by the Occupational Accidents and Professional Disease No 16.744 Act.

Design

Cross-sectional on registries of the Chilean Worker's Health and Safety National Information System, specifically focusing on the Fatal Work Accidents Registry of the Social Security Superintendence.

Study population

Secondary data analysis on all 815 cases of occupational injury-related deaths registered in 2014 and 2015 in Chile and that were accredited by the Social Security Superintendence up to March 2016.

Outcome measures

Variables relating to employer, workers and the events were analysed.

Results

The overall mortality rate for all injuries, both at work and during commuting, per 100 000 workers affiliated to the occupational social security system, was 7.2 for 2014 and 7.3 for 2015. For 2014, the highest mortality rates occurred in the transport and communications sectors (20.15) and the mining sector (18.17), while for 2015 the highest rates were found in the fishing industry (11.3) and in mining (12.1). Seventy-two per cent of cases occurred in small and medium-sized enterprises. Half of the companies that had work-related fatal injuries did not have a risk prevention department. Twenty-two per cent (121) of the companies had previous labour law infractions. The four activities most affected by workers' deaths in the two study years were freight land transport, engineering works under construction, minor works under construction and construction of complete buildings or parts of buildings. Half of all fatal injuries occurred in workers who had been employed for less than a year in their company.

Conclusions

This descriptive study provides valuable insight into the current national registry on occupational deaths in Chile. While containing valuable information, the registry was not designed for epidemiological surveillance. Further efforts are needed to achieve a proper epidemiological integration of surveillance data.

https://ift.tt/2JnaGs5

Sexual assaults in individuals with visual impairment: a cross-sectional study of a Norwegian sample

Objective

To examine the prevalence of sexual assaults among individuals with visual impairment (VI) compared with the general population and to investigate the association between sexual assault and outcomes of self-efficacy and life satisfaction.

Design

Cross-sectional interview-based study conducted between February and May 2017.

Participants

A probability sample of adults with VI (≥18 years) who were members of the Norwegian Association of the Blind and Partially Sighted. A total of 736 (61%) members participated, of whom 55% were of female gender. We obtained norm data for sexual assaults from a representative survey of the general Norwegian population.

Outcome measures

Sexual assaults (Life Event Checklist for DSM-5), self-efficacy (General Self-Efficacy Scale) and life satisfaction (Cantril's Ladder of Life Satisfaction).

Results

The prevalence of sexual assaults (rape, attempted rape and forced into sexual acts) in the VI population was 17.4% (95% CI 14.0 to 21.4) among women and 2.4% (95% CI 1.2 to 4.7) among men. For women, the VI population had higher rates of sexual assaults across age strata than the general population. For men, no significant differences were found. In the population of people with VI, the risk of sexual assault was greater for those having other impairments in addition to the vision loss. Individuals with VI who experienced sexual assaults had lower levels of self-efficacy (adjusted relative risk (ARR): 0.18, 95% CI 0.05 to 0.61) and life satisfaction (ARR: 0.31, 95% CI 0.19 to 0.50) than others.

Conclusions

The risk of experiencing sexual assault appears to be higher in individuals with VI than in the general population. Preventive measures as well as psychosocial care for those who have been exposed are needed.

https://ift.tt/2LE45X1

Ultrasound-guided tendon fenestration versus open-release surgery for the treatment of chronic lateral epicondylosis of the elbow: protocol for a prospective, randomised, single blinded study

Introduction

Chronic lateral epicondylosis (CLE) of the elbow is a prevalent condition among middle-aged people with no consensus on optimal care management but for which surgery is generally accepted as a second intention treatment. Among conservative treatment options, ultrasound (US)-guided fenestration has shown encouraging results that should be explored before surgery is considered. The primary objective of this study is to compare the efficacy of US-guided fenestration with open-release surgery in patients with failure to improve following a minimum 6 months of conservative treatment.

Methods and analysis

This study protocol entails a two-arm, single-blinded, randomised, controlled design. Sixty-four eligible patients with clinically confirmed CLE will be assigned to either US-guided fenestration or open-release surgery. Fisher's exact test will be used to compare the proportion of patients reporting a change of 11/100 points or more in the Patient Rated Tennis Elbow Evaluation score at 6 months, according to an intention-to-treat analysis. Secondary analyses will compare the two treatment groups in terms of pain and disability, functional limitations at work, pain-free grip strength, medication burden, patients' global impression of change and level of satisfaction at 6 weeks, 3, 6 and 12 months, using mixed linear models for repeated measures or Fisher's exact test, as appropriate. Finally, recursive partitioning analyses will investigate US and elastography parameters as predictors of treatment success at 6 and 12 months. This data will contribute to evidence-based treatment guidelines for CLE and explore the value of imaging biomarkers to improve risk stratification plans and assist clinicians.

Ethics and dissemination

The study has been approved by the Research Ethics Board of our institution on 23 March 2016 (REB 15.327). In case of important protocol modifications, a new version of the protocol with appropriate amendments will be submitted to the REB for approval. Study results will be published in peer-reviewed journals and presented at local, national and international conferences.

Trial registration number

NCT02710682.

https://ift.tt/2JohjdI

Cohort profile: the Geoscience and Health Cohort Consortium (GECCO) in the Netherlands

Purpose

In the Netherlands, a great variety of objectively measured geo-data is available, but these data are scattered and measured at varying spatial and temporal scales. The centralisation of these geo-data and the linkage of these data to individual-level data from longitudinal cohort studies enable large-scale epidemiological research on the impact of the environment on public health in the Netherlands. In the Geoscience and Health Cohort Consortium (GECCO), six large-scale and ongoing cohort studies have been enriched with a variety of existing geo-data. Here, we introduce GECCO by describing: (1) the phenotypes of the involved cohort studies, (2) the collected geo-data and their sources, (3) the methodology that was used to link the collected geo-data to individual cohort studies, (4) the similarity of commonly used geo-data between our consortium and the nationwide situation in the Netherlands and (5) the distribution of geo-data within our consortium.

Participants

GECCO includes participants from six prospective cohort studies (eg, 44 657 respondents (18–100 years) in 2006) and it covers all municipalities in the Netherlands. Using postal code information of the participants, geo-data on the address-level, postal code-level as well as neighbourhood-level could be linked to individual-level cohort data.

Findings to date

The geo-data could be successfully linked to almost all respondents of all cohort studies, with successful data-linkage rates ranging from 97.1% to 100.0% between cohort studies. The results show variability in geo-data within and across cohorts. GECCO increases power of analyses, provides opportunities for cross-checking and replication, ensures sufficient geographical variation in environmental determinants and allows for nuanced analyses on specific subgroups.

Future plans

GECCO offers unique opportunities for (longitudinal) studies on the complex relationships between the environment and health outcomes. For example, GECCO will be used for further research on environmental determinants of physical/psychosocial functioning and lifestyle behaviours.

https://ift.tt/2HxlH4k

Childrens views on research without prior consent in emergency situations: a UK qualitative study

Objectives

We explored children's views on research without prior consent (RWPC) and sought to identify ways of involving children in research discussions.

Design

Qualitative interview study.

Setting

Participants were recruited through a UK children's hospital and online advertising.

Participants

16 children aged 7–15 years with a diagnosis of asthma (n=14) or anaphylaxis (n=2) with recent (<12 months) experience of emergency care.

Results

Children were keen to be included in medical research and viewed RWPC as acceptable in emergency situations if trial interventions were judged safe. Children trusted that doctors would know about their trial participation and act in their best interests. All felt that children should be informed about the research following their recovery and involved in discussions with a clinician or their parent(s) about the use of data already collected as well as continued participation in the trial (if applicable). Participants suggested methods to inform children about their trial participation including an animation.

Conclusions

Children supported, and were keen to be involved in, clinical trials in emergency situations. We present guidance and an animation that practitioners and parents might use to involve children in trial discussions following their recovery.

https://ift.tt/2JqGOev

Accuracy, reproducibility and costs of different laboratory assays for the monitoring of unfractionated heparin in clinical practice: a prospective evaluation study and survey among Swiss institutions

Objectives

To investigate the accuracy, reproducibility and costs of different laboratory assays for the monitoring of unfractionated heparin (UFH) in clinical practice and to study test utilisation in Switzerland.

Design

Prospective evaluation study and survey among Swiss hospitals and laboratories.

Setting

Secondary care hospital in rural Switzerland (evaluation study); all Swiss hospitals and laboratories (survey).

Participants

All consecutive patients, monitored for treatment with UFH during two time periods, were included (May to July 2014 and January to February 2015; n=254).

Outcome measures

Results of activated partial thromboplastin time (aPTT), thrombin time (TT), prothrombinase-induced clotting time (PiCT) and anti-Xa activity with respect to UFH concentration

Results

Spearman's correlation coefficient (r_s) with regard to anti-Xa activity was 0.68 (95% CI 0.60 to 0.75) for aPTT, 0.79 (0.69 to 0.86) for TT and 0.94 (0.93 to 0.95) for PiCT. The correlation (r_s) between anti-Xa activity and heparin concentration as determined by spiking plasma samples was 1.0 (1.0 to 1.0). The coefficient of variation was at most 5% for PiCT and anti-Xa activity (within-run as well as day-to-day variability). The total costs per test in Swiss Francs (SFr) were SFr23.40 for aPTT, SFr33.30 for TT, SFr15.70 for PiCT and SFr24.15 for anti-Xa activity. The various tests were employed in Swiss institutions with the following frequencies: aPTT 53.2%, TT 21.6%, anti-Xa activity 7.2%, PiCT 1.4%; 16.6% of hospitals performed more than one test.

Conclusions

The accuracy and reproducibility of PiCT and anti-Xa activity for monitoring of UFH was superior, and analytical costs were equivalent to or lower than aPTT and TT.

https://ift.tt/2LxXcX5

Associations between anthropometric indices, blood pressure and physical fitness performance in young Swiss men: a cross-sectional study

Objectives

To assess the benefit of waist circumference (WC) measurements during routine conscription medical examination in two military conscription centres in Switzerland. We compared the prevalence of overweight and obesity assessed by body mass index (BMI) with the prevalence of elevated disease risks assessed by WC and waist-to-height ratio (WHtR). We investigated how these measures were associated with systolic blood pressure, physical fitness performance and socioeconomic determinants.

Design

Cross-sectional survey.

Setting

Two Swiss conscription centres in 2016.

Participants

1548 Swiss male conscripts, 18–22 years old.

Main outcome

Prevalences of elevated WC, WHtR and BMI values according to WHO categories. Secondary outcomes include systolic blood pressure, physical fitness performance and endurance performance.

Results

Using BMI cut-points, 25.0% of all conscripts were overweight or obese. When applying WC cut-points, 9.2% had an increased disease risk, while 14.8% of the conscripts were at risk using WHtR cut-points. In the BMI range of 25.0–27.4 kg/m², 3.6% showed an increased disease risk when using WC and 24.6% when using WHtR cut-points. Of the conscripts with a BMI of 27.5–29.9 kg/m², 72.4% had an increased disease risk using WHtR, and 42.5% when using WC cut-points. Determinants of elevated BMI, WC and WHtR were low occupational status, rural residential area, older age and location in central and Northwest Switzerland. Systolic blood pressure increased with increasing BMI, WC and WHtR. Physical fitness and endurance test performances decreased with increasing BMI, WC and WHtR.

Conclusion

In addition to BMI, WC and WHtR add relevant information to the health assessment of young men. However, the prevalence of overweight/increased health risk differed when using BMI, WC or WHtR. Further studies should include measures of body composition to test whether these differences arise from muscular young men within the overweight BMI range, who had a normal WC.

https://ift.tt/2JqgW2j

Awareness and attitudes toward corneal donation: challenges and opportunities

https://ift.tt/2JFSEjZ

EFFECTS OF CONCENTRATED GROWTH FACTORS (CGF) ON THE QUALITY OF THE INDUCED MEMBRANE IN MASQUELET'S TECHNIQUE - AN EXPERIMENTAL STUDY IN RABBITS

Publication date: Available online 8 June 2018
Source:Injury
Author(s): Orkun Yılmaz, Ahmet Özmeriç, Kadir Bahadır Alemdaroğlu, Pınar Celepli, Sema Hücümenoğlu, Özgür Şahin
AimsThe aim of the study was to test if the addition of CGF to the Masquelet technique contributes to the quality of the membrane formed surrounding the polymethylmethacrylate (PMMA), in terms of inflammation, proliferation and vasculazition in the Masquelet technique in the early and late phases in a rabbit model.Materials and MethodsA critical bone defect of 15 mm was created in radius diaphysis, leaving 3 cm of intact bone to the joint. To mimic the Masquelet technique and to increase stability, a 6-hole 1.5 mm plate with two screws was applied, although it was initialy stable because of the inherently fixed ulna and radius both proximally and distally in the rabbits. Group 1 and Group 3, were soleley treated with the Masquelet technique as control groups, and were sacrificed at 3 and 6 weeks, respectively. Group 2 and Group 4, were treated with the Masquelet technique + CGF prepared from the rabbit blood groups, and were sacrificed at 3 and 6 weeks, respectively. The groups were compared histopathologically and immunohistochemically, in respect of the means of thickness of the membrane and ratio of elastic fibers, membrane vascularization (CD31), inflammation (MAC387), proliferation (Ki67), and presence of stem cells (STRO-1).ResultsThickness of the membrane and CD31 values were significantly higher in Group 4 than Group 3 (p = 0.004 for both). MAC387 was statistically significantly higher in Group 2 compared to Group 1 and Group 4 compared to Group 3 (p = 0.04 for both). Ki67 was significantly higher in Group 2 compared to Group 1 and Group 4 compared to Group 3 (p = 0.05 and p = 0.006, respectively). Proliferation in the membrane was statistically significantly higher in Group 2 compared to Group 1 (p = 0.05). Likewise, the proliferation index of Group 4 was statistically significantly higher than Group 3 (p = 0.06). STRO-1 was significantly higher in Group 2 compared to Group 1 (p = 0,036).ConclusionThe addition of CGF to the Masquelet technique contributes to the quality of the membrane formed, in respect of inducing inflammation and proliferation, maintaining vascularization on large diaphyseal bone defects, and increasing the number of stem cells.



https://ift.tt/2JoNVUK

Editorial Board/Publication Information

Publication date: June 2018
Source:Injury, Volume 49, Issue 6





https://ift.tt/2Hz5BHl

Profile of litigation for orthopaedic trauma

Publication date: June 2018
Source:Injury, Volume 49, Issue 6
Author(s): M. Gathen, K.G. Makridis, P.V. Giannoudis




https://ift.tt/2JoNXvQ

Clinical characteristics and long-term visual outcome of severe phenotypes of chronic central serous chorioretinopathy

https://ift.tt/2HzBKyn

Blood cell count indexes as predictors of outcomes in advanced non-small-cell lung cancer patients treated with Nivolumab

Abstract

Lung cancer is the most common malignancy worldwide. Despite significant advances in diagnosis and treatment, mortality rates remain extremely high, close to incidence rates. Several targeted therapies have been recently introduced for the treatment of non-small cell lung cancer (NSCLC), the most common type of lung cancer. Nivolumab, a monoclonal antibody that targets programmed death-1 (PD-1), was the first immune checkpoint inhibitor approved for the treatment of patients with advanced/metastatic NSCLC not responding to platinum-based chemotherapy. Biomarkers predicting response to these therapies would allow early identification of non-responders and timely implementation of appropriate combination strategies, avoiding inadequate and expensive therapies. The role of the neutrophil to lymphocyte ratio and other blood cell count indexes as possible biomarkers of response has been recently investigated. We discuss the encouraging results reported on the topic, provide new data from our personal experience, and discuss opportunities for further research.

https://ift.tt/2JuRzs6

Insomnia Disorder and Brain’s Default-Mode Network

Abstract

Purpose of Review

Insomnia disorder (ID) is a prevalent sleep disorder that significantly compromises the physical and mental health of individuals. This article reviews novel approaches in the study of brain networks and impaired function in ID through the application of modern neuroimaging techniques such as functional magnetic resonance imaging (fMRI).

Recent Findings

The default-mode network (DMN) is presumed to be correlated with self-referential information processing, and it appears to be altered or unbalanced in insomnia.

Summary

A growing body of evidence suggests the lack of deactivation of brain regions comprising the DMN when insomnia patients are at rest. Moreover, core areas of the DMN demonstrate greater activation in insomnia patients when compared to healthy controls in self-referential related tasks. Despite the few studies on the topic, underpinning the correlation between abnormal DMN activity and ID deserves further attention in the future. Implications for therapeutics are briefly outlined.

https://ift.tt/2MdoKSO

Cancers, Vol. 10, Pages 191: WIP-YAP/TAZ as A New Pro-Oncogenic Pathway in Glioma

Cancers, Vol. 10, Pages 191: WIP-YAP/TAZ as A New Pro-Oncogenic Pathway in Glioma

Cancers doi: 10.3390/cancers10060191

Authors: Sergio Rivas Inés M. Antón Francisco Wandosell

Wild-type p53 (wtp53) is described as a tumour suppressor gene, and mutations in p53 occur in many human cancers. Indeed, in high-grade malignant glioma, numerous molecular genetics studies have established central roles of RTK-PI3K-PTEN and ARF-MDM2-p53 INK4a-RB pathways in promoting oncogenic capacity. Deregulation of these signalling pathways, among others, drives changes in the glial/stem cell state and environment that permit autonomous growth. The initially transformed cell may undergo subsequent modifications, acquiring a more complete tumour-initiating phenotype responsible for disease advancement to stages that are more aggressive. We recently established that the oncogenic activity of mutant p53 (mtp53) is driven by the actin cytoskeleton-associated protein WIP (WASP-interacting protein), correlated with tumour growth, and more importantly that both proteins are responsible for the tumour-initiating cell phenotype. We reported that WIP knockdown in mtp53-expressing glioblastoma greatly reduced proliferation and growth capacity of cancer stem cell (CSC)-like cells and decreased CSC-like markers, such as hyaluronic acid receptor (CD44), prominin-1 (CD133), yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ). We thus propose a new CSC signalling pathway downstream of mtp53 in which Akt regulates WIP and controls YAP/TAZ stability. WIP drives a mechanism that stimulates growth signals, promoting YAP/TAZ and &beta;-catenin stability in a Hippo-independent fashion, which allows cells to coordinate processes such as proliferation, stemness and invasiveness, which are key factors in cancer progression. Based on this multistep tumourigenic model, it is tantalizing to propose that WIP inhibitors may be applied as an effective anti-cancer therapy.

https://ift.tt/2sNqj0O

A prototype assembled 3D-printed phantom of the glenohumeral joint for fluoroscopic-guided shoulder arthrography

Abstract

Purpose

To describe the methodology of constructing a three-dimensional (3D) printed model of the glenohumeral joint, to serve as an interventional phantom for fluoroscopy-guided shoulder arthrography training.

Materials and methods

The osseous structures, intra-articular space and skin surface of the shoulder were digitally extracted as separate 3D meshes from a normal CT arthrogram of the shoulder, using commercially available software. The osseous structures were 3D-printed in gypsum, a fluoroscopically radiopaque mineral, using binder jet technology. The joint capsule was 3D printed with rubber-like TangoPlus material, using PolyJet technology. The capsule was secured to the humeral head and glenoid to create a sealed intra-articular space. A polyamide mold of the skin was printed using selective laser sintering. The joint was stabilized inside the mold, and the surrounding soft tissues were cast in silicone of varying densities. Fluoroscopically-guided shoulder arthrography was performed using anterior, posterior, and rotator interval approaches. CT arthrographic imaging of the phantom was also performed.

Results

A life-size phantom of the glenohumeral joint was constructed. The radiopaque osseous structures replicated in-vivo osseous corticomedullary differentiation, with dense cortical bone and less dense medullary cancellous bone. The glenoid labrum was successfully integrated into the printed capsule, and visualized on CT arthrography. The phantom was repeatedly used to perform shoulder arthrography using all three conventional approaches, and simulated the in vivo challenges of needle guidance.

Conclusions

3D printing of a complex capsule, such as the glenohumeral joint, is possible with this technique. Such a model can serve as a valuable training tool.

https://ift.tt/2JyccDB