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Σάββατο 27 Ιανουαρίου 2018

CC Nerd-The Case of the Inverted Premise

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No mode of ventilation is burdened with more emotional baggage than airway pressure release ventilation (APRV). The mere suggestion of its use is met with either the delight of recognizing an old friend whom you are meeting for the first time, or the type of disgust typically reserved for the likes of snake oil salesmen. […]

EMCrit Project by Rory Spiegel.



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Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

This study investigated associations between SNPs in genes encoding metabolizing drug enzymes and laboratory parameters in sickle cell anemia patients under hydroxyurea (SCA-HU+). We evaluated hematologic and biochemical parameters by electronic methods and SNPs by PCR-RFLP and multiplex PCR in 35 SCA-HU+ patients and 67 SCA-HU− patients. The HbS, total cholesterol, lactate dehydrogenase, aspartate aminotransferase, total bilirubin and fractions levels, and leukocyte, eosinophil, monocyte, and erythroblast counts were reduced in SCA-HU+ patients (). Moreover, they presented higher HbF, C-reactive protein, and ferritin levels and elevated MCH and MCV values (). Genotype frequencies of variants GA + AA of MPO −463G>A and c1c2 + c2c2 of CYP2E1 −1293G>C/−1053C>T were higher in SCA-HU+ patients (). Independent associations were found between the variant A allele and lower total cholesterol, between c2 allele and low alpha-1 antitrypsin and between the null GSTT1 variant and high indirect and total bilirubin in SCA-HU+ patients. In SCA-HU− patients, independent associations were found between the variant A allele and high uric acid and between c2 allele and high urea. Our results suggest that SNPs MPO −463G>A, CYP2E1 −1293G>C/−1053C>T, and GSTT1 can be associated with alterations in lipid, inflammatory, renal, hemolytic, and hepatic profiles. However, further studies are needed to elucidate these associations.

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A Comprehensive Review of the Pharmacologic Management of Uterine Leiomyoma

Uterine leiomyomata are the most common benign tumors of the gynecologic tract impacting up to 80% of women by 50 years of age. It is well established that these tumors are the leading cause for hysterectomy with an estimated total financial burden greater than $30 billion per year in the United States. However, for the woman who desires future fertility or is a poor surgical candidate, definitive management with hysterectomy is not an optimal management plan. Typical gynecologic symptoms of leiomyoma include infertility, abnormal uterine bleeding (AUB)/heavy menstrual bleeding (HMB) and/or intermenstrual bleeding (IMB) with resulting iron-deficiency anemia, pelvic pressure and pain, urinary incontinence, and dysmenorrhea. The morbidity caused by these tumors is directly attributable to increases in tumor burden. Interestingly, leiomyoma cells within a tumor do not rapidly proliferate, but rather the increase in tumor size is secondary to production of an excessive, stable, and aberrant extracellular matrix (ECM) made of disorganized collagens and proteoglycans. As a result, medical management should induce leiomyoma cells toward dissolution of the extracellular matrix, as well as halting or inhibiting cellular proliferation. Herein, we review the current literature regarding the medical management of uterine leiomyoma.

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The Difference in Cervical Vertebral Skeletal Maturation between Cleft Lip/Palate and Non-Cleft Lip/Palate Orthodontic Patients

Objective. The aim was to evaluate differences in the cervical vertebral skeletal maturity of unilateral cleft lip and palate (UCLP) and non-cleft lip/palate (non-CLP) Saudi male orthodontic patients. Method. This cross-sectional multicenter study took place at the dental school, King Saud University and King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, between October 2014 and September 2015. The records of Saudi male orthodontic patients with UCLP were collected. Cervical vertebral maturation was assessed using their cephalometric radiographs. The records of 138 age-matched non-CLP Saudi male orthodontic patients served as controls. Results. There was a significant difference in skeletal maturity between the UCLP and non-CLP groups, as evident in the delayed skeletal development among the UCLP participants. Moreover, pubertal growth spurt onset was significantly earlier in the non-cleft participants in comparison with the UCLP participants . Conclusions. There is delayed skeletal maturity among the UCLP Saudi male population in comparison with their non-CLP age-matched peers.

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Health Risk Behaviour among Adolescents Living with HIV in Sub-Saharan Africa: A Systematic Review and Meta-Analysis

The burden of health risk behaviour (HRB) among adolescents living with HIV (ALWHIV) in sub-Saharan Africa (SSA) is currently unknown. A systematic search for publications on HRB among ALWHIV in SSA was conducted in PubMed, Embase, PsycINFO, and Applied Social Sciences Index and Abstracts databases. Results were summarized following PRISMA guidelines for systematic reviews and meta-analyses. Heterogeneity was assessed by the DerSimonian and Laird method and the pooled estimates were computed. Prevalence of current condom nonuse behaviour was at 59.8% (95% CI: 47.9–71.3%), risky sexual partnerships at 32.9% (95% CI: 15.4–53.2%), transactional sex at 20.1% (95% CI: 9.2–33.8%), and the experience of sexual violence at 21.4% (95% CI: 16.3–27.0%) among ALWHIV. From this meta-analysis, we did not find statistically significant differences in pooled estimates of HRB prevalence between ALWHIV and HIV uninfected adolescents. However, there was mixed evidence on the occurrence of alcohol and drug use behaviour. Overall, we found that research on HRB among ALWHIV tends to focus on behaviour specific to sexual risk. With such a high burden of HRB for the individuals as well as society, these findings highlight an unmet need for age-appropriate interventions to address the behavioural needs of these adolescents.

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Effects of Fibers on Color and Translucency Changes of Bulk-Fill and Anterior Composites after Accelerated Aging

The aim of this study was to determine the effects of glass and polyethylene fibers on the color and translucency change of bulk-fill and anterior composites before and after artificial accelerated aging (AAA). Two types of teflon molds were used to fabricate samples which were 13 mm in diameter and, respectively, 2 mm and 4 mm in height. Polyethylene fiber (PF) and glass fiber (GF) were incorporated in the middle of the composite samples. Color and translucency changes of each composite were evaluated before and after AAA with spectrophotometer. ANOVA and Tukey's HSD post hoc statistical analysis were used at a significance level of 0.05. Before AAA (for anterior composites), there were no significant differences in and parameters among the three groups (); there were no significant differences in parameter between PF and GF groups or in TP between GF and control groups () (for bulk-fill composites). After AAA, there were no significant differences in parameter between GF and control groups, in parameter between PF and control groups, in parameter among all groups, or in TP parameter between GF and control groups (). Fiber reinforcement led to color and TP change in both anterior and bulk-fill resin composites.

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Chronic Intake of Commercial Sweeteners Induces Changes in Feeding Behavior and Signaling Pathways Related to the Control of Appetite in BALB/c Mice

Nonnutritive sweetener use is a common practice worldwide. Although considered safe for human consumption, accumulating evidence suggests these compounds may affect metabolic homeostasis; however, there is no consensus on the role of frequent sweetener intake in appetite and weight loss. We sought to determine whether frequent intake of commercial sweeteners induces changes in the JAK2/STAT3 signaling pathway in the brain of mice, as it is involved in the regulation of appetite and body composition. We supplemented adult BALB/c mice with sucrose, steviol glycosides (SG), or sucralose, daily, for 6 weeks. After supplementation, we evaluated body composition and expression of total and phosphorylated JAK2, STAT3, and Akt, as well as SOCS3 and ObRb, in brain tissue. Our results show that frequent intake of commercial SG decreases energy intake, adiposity, and weight gain in male animals, while increasing the expression of pJAK2 and pSTAT3 in the brain, whereas sucralose increases weight gain and pJAK2 expression in females. Our results suggest that chronic intake of commercial sweeteners elicits changes in signaling pathways that have been related to the control of appetite and energy balance in vivo, which may have relevant consequences for the nutritional state and long term health of the organism.

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Mechanical and Controlled PRP Injections in Patients Affected by Androgenetic Alopecia

This paper aims to describe the interfollicular autologous platelet-rich plasma injections (0.20 mL x cm2) in the scalp of 23 patients affected by androgenetic alopecia at a depth of 5 mm using a medical injector gun equipped with a 30 gauge needle, in three sessions.

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Measurement & Analysis of the Temporal Discrimination Threshold Applied to Cervical Dystonia

Methods for the measurement and analysis of the temporal discrimination threshold are presented, and its application to the study of the pathogenesis of cervical dystonia are discussed.

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Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage

Objective

Liver injury impacts hepatic inflammation in part via Toll-like receptor (TLR) signalling. Triggering receptor expressed on myeloid cells 2 (TREM-2) modulates TLR4-mediated inflammation in bone marrow (BM)-derived macrophages but its function in liver injury is unknown. Here we hypothesised that the anti-inflammatory effects of TREM-2 on TLR signalling may limit hepatic injury.

Design

TREM-2 expression was analysed in livers of humans with various forms of liver injury compared with control individuals. Acute and chronic liver injury models were performed in wild type and Trem-2-/- mice. Primary liver cells from both genotypes of mice were isolated for in vitro experiments.

Results

TREM-2 was expressed on non-parenchymal hepatic cells and induced during liver injury in mice and man. Mice lacking TREM-2 exhibited heightened liver damage and inflammation during acute and repetitive carbon tetrachloride and acetaminophen (APAP) intoxication, the latter of which TREM-2 deficiency was remarkably associated with worsened survival. Liver damage in Trem-2-/- mice following chronic injury and APAP challenge was associated with elevated hepatic lipid peroxidation and macrophage content. BM transplantation experiments and cellular reactive oxygen species assays revealed effects of TREM-2 in the context of chronic injury depended on both immune and resident TREM-2 expression. Consistent with effects of TREM-2 on inflammation-associated injury, primary hepatic macrophages and hepatic stellate cells lacking TREM-2 exhibited augmented TLR4-driven proinflammatory responses.

Conclusion

Our data indicate that by acting as a natural brake on inflammation during hepatocellular injury, TREM-2 is a critical regulator of diverse types of hepatotoxic injury.



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Prognostic significance of tumor-infiltrating lymphocytes in non-disseminated nasopharyngeal carcinoma: A large-scale cohort study

Abstract

The American Joint Committee on Cancer (AJCC) staging system is inadequate for an accurate prognosis in nasopharyngeal carcinoma (NPC). Thus, new biomarkers are under intense investigation. Here, we investigated whether the density of TILs could predict prognosis in NPC. First, we used 1490 cases of nasopharyngeal carcinoma samples from two independent cohorts to evaluate the density and distribution of tumor-infiltrating lymphocytes (TILs). Second, in one cohort, we assessed associations between TILs and clinical outcomes in 593 randomly selected samples (defined as the training set) and validated findings in the remaining 593 samples (defined as the validation set). Furthermore, we confirmed the prognostic value of TILs in a second independent cohort of 304 cases (defined as the independent set). Based on multivariable Cox regression analysis, we also established an effective prognostic nomogram including TILs to improve accuracy in predicting disease-free survival (DFS) for patients with non-disseminated NPC. We found that high TILs in the training set were significantly associated with favorable DFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28–0.58, P < 0.001], overall survival (OS, HR 0.42, 95% CI 0.27–0.64, P < 0.001), distant metastasis-free survival (DMFS, HR 0.37, 95% CI 0.23–0.58, P < 0.001) and local-regional recurrent free survival (LRRFS, HR 0.43, 95% CI 0.25–0.73, P = 0.002). Multivariate analysis showed that TILs are an independent prognostic indicator for DFS in all cohorts. In summary, this study indicated that TILs may reflect the immunological heterogeneity of NPC and could represent a new prognostic biomarker. This article is protected by copyright. All rights reserved.



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Comprehensive circRNA expression profile and construction of circRNA-associated ceRNA network in fur skin

Abstract

Circular RNA (circRNA), a class of non-coding RNAs, is a new group of RNAs that are related to tumorigenesis. The role of circRNAs in various diseases has been already highlighted. However, the expression levels and functions of circRNAs related to the melanocytes in the skin are poorly understood. RNA sequence was performed to analyze the expression profiles of circRNAs in black fur skin and white fur skin during different differentiation stages and investigate the relevant metabolism mechanisms. Differentially expressed circRNAs were detected using empirical Bayes sequencing (EBSeq) and then verified through the quantitative real-time PCR method. The EQSeq analysis of circRNAs identified 11 downregulated and 32 upregulated circRNAs in the embryo of black fur skin and white fur skin, as well as 21 downregulated and 17 upregulated circRNA in the postnatal stage. A circRNA–microRNA (miRNA)– messenger RNA (mRNA) network was established to predict the circRNA targets. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied to enrich the mRNA data further. Results showed that the specific mRNAs mainly involved in the transcription- related GOs, especially GO:0042802, GO:0005080 and GO:0032403, demonstrate their specific actions in transcriptional regulation. In the circRNA–miRNA–mRNA network, the most enriched GO terms of the mRNAs were pigmentation, protein autophosphorylation, and protein complex. Therefore, the circRNA–miRNA–mRNA pathway may reveal novel mechanisms for pigmentation, and circRNAs may serve as candidates in pigmentation.

This article is protected by copyright. All rights reserved.



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Study protocol for a cluster randomised controlled factorial design trial to assess the effectiveness and feasibility of reactive focal mass drug administration and vector control to reduce malaria transmission in the low endemic setting of Namibia

Introduction

To interrupt malaria transmission, strategies must target the parasite reservoir in both humans and mosquitos. Testing of community members linked to an index case, termed reactive case detection (RACD), is commonly implemented in low transmission areas, though its impact may be limited by the sensitivity of current diagnostics. Indoor residual spraying (IRS) before malaria season is a cornerstone of vector control efforts. Despite their implementation in Namibia, a country approaching elimination, these methods have been met with recent plateaus in transmission reduction. This study evaluates the effectiveness and feasibility of two new targeted strategies, reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in Namibia.

Methods and analysis

This is an open-label cluster randomised controlled trial with 2x2 factorial design. The interventions include: rfMDA (presumptive treatment with artemether-lumefantrine (AL)) versus RACD (rapid diagnostic testing and treatment using AL) and RAVC (IRS with Acellic 300CS) versus no RAVC. Factorial design also enables comparison of the combined rfMDA+RAVC intervention to RACD. Participants living in 56 enumeration areas will be randomised to one of four arms: rfMDA, rfMDA+RAVC, RACD or RACD+RAVC. These interventions, triggered by index cases detected at health facilities, will be targeted to individuals residing within 500 m of an index. The primary outcome is cumulative incidence of locally acquired malaria detected at health facilities over 1 year. Secondary outcomes include seroprevalence, infection prevalence, intervention coverage, safety, acceptability, adherence, cost and cost-effectiveness.

Ethics and dissemination

Findings will be reported on clinicaltrials.gov, in peer-reviewed publications and through stakeholder meetings with MoHSS and community leaders in Namibia.

Trial registration number

NCT02610400; Pre-results.



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Maternal and birth cohort studies in the Gulf Cooperation Council countries: protocol for a systematic review and narrative evaluation

Introduction

Cohort studies have revealed that genetic, socioeconomic, communicable and non-communicable diseases, and environmental exposures during pregnancy may influence the mother and her pregnancy, birth delivery and her offspring. Numerous studies have been conducted in the Gulf Cooperation Council (GCC) countries to examine maternal and birth health. The objectives of this protocol for a systematic review are to systematically review and characterise the exposures and outcomes that have been examined in the mother and birth cohort studies in the GCC region, and to summarise the strength of association between key maternal exposures during pregnancy (ie, body mass index) and different health-related outcomes (ie, mode of birth delivery). The review will then synthesise and characterise the consequent health implications and will serve as a platform to help identify areas that are overlooked, point out limitations of studies and provide recommendations for future cohort studies.

Methods and analysis

Medline, Embase, Cochrane Library and Web of Science electronic databases will be comprehensively searched. Two reviewers will independently screen each study for eligibility, and where discrepancies arise they will be discussed and resolved; otherwise a third reviewer will be consulted. The two reviewers will also independently extract data into a predefined Excel spreadsheet. The included studies will be categorised on the basis of whether the participant is a mother, infant or mother–infant dyad. Outcome variables will be divided along two distinctions: mother or infant. Exposure variables will be divided into six domains: psychosocial, biological, environmental, medical/medical services, maternal/reproductive and perinatal/child. Studies are expected to be of heterogeneous nature; therefore, quantitative syntheses might be limited.

Ethics and dissemination

There is no primary data collection; therefore, ethical review is not necessary. The findings of this review will be disseminated in a peer-reviewed journal and presented at relevant conferences.

PROSPERO registration number

CRD42017068910.



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Students satisfaction and perceived impact on knowledge, attitudes and skills after a 2-day course in scientific writing: a prospective longitudinal study in Spain

Objectives

This study aimed to determine students' satisfaction with a 2-day course on scientific writing in health sciences and to assess their perceptions of the long-term impact on their knowledge, attitudes and skills.

Setting

27 iterations of a 2-day course on writing and publishing scientific articles in health sciences.

Participants

741 students attending the 27 courses.

Design

Prospective longitudinal study.

Primary and secondary outcome measures

Immediately after each course, students completed a first questionnaire, rating their satisfaction with different aspects of the classroom sessions on a Likert scale (0–5). Approximately 2 years after the course, students completed a follow-up questionnaire, using a Likert scale (0–4) to rate their knowledge, skills and attitudes in relation to scientific writing before and after attending the course.

Results

741 students (70% women) participated in the 27 iterations of the course; 568 (76.8%) completed the first questionnaire and 182 (24.6%) completed the follow-up questionnaire. The first questionnaire reflected high overall satisfaction (mean score, 4.6). In the second questionnaire, students reported that the course had improved their knowledge (mean improvement: 1.6; 95% CI 1.6 to 1.7), attitudes (mean improvement: 1.3; 95% CI 1.2 to 1.4) and skills (mean improvement: 1.4; 95% CI 1.3 to 1.4) related to writing and publishing scientific papers. Most respondents (n=145, 79.7%) had participated in drafting a scientific paper after the course; in this subgroup, all the specific writing skills assessed in the second questionnaire significantly improved.

Conclusions

Students were satisfied with the format and the contents of the course, and those who responded to the follow-up survey considered that the course had improved their knowledge, attitudes and skills in relation to scientific writing and publishing. Courses are particularly important in countries without strong traditions in scientific publication.



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Suicide bereavement: piloting a longitudinal study in Australia

Objectives

The pilot study were (1) to test the technical and administrative feasibility of a full-scale study, including recruitment process, response and retention rate, questionnaire design for an investigation to improve understanding of the suicide bereavement processes compared with bereavement by sudden deaths and (2) to present the differences and changes in the main outcomes—grief reactions of close relatives exposed to suicide and sudden death over 2 years.

Design

A longitudinal prospective study comparing bereavement by suicide to other types of sudden deaths over time (6, 12 and 24 months).

Setting

Queensland, Australia.

Participants

25 suicide-bereaved and 15 sudden-death-bereaved persons.

Outcome measures

Grief reactions (measured with the Grief Experience Questionnaire).

Results

The response rate was 52.1% in the suicide bereaved and 45.5% in the sudden-death group. There was a small number of dropouts, with the retention rate over 85% for both groups. Linear mixed modelling for repeated measures showed a significant group effect (higher in suicide bereaved) for total grief, responsibility, rejection and unique reactions. A significant time effect (reduction) was measured for total grief, somatic reactions, general grief reactions and search for explanation. One significant time and group interaction was measured; rejection showed a decline in suicide and an increase in sudden-death bereaved.

Conclusions

The pilot study presented the appropriateness of the study methodology. This type of study has implications for counselling and treating people bereaved by suicide and for designing postvention activities.



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Needs of informal caregivers across the caregiving course in amyotrophic lateral sclerosis: a qualitative analysis

Objectives

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a debilitating terminal condition. Informal caregivers are key figures in ALS care provision. The physical, psychological and emotional impact of providing care in the home requires appropriate assistance and support. The objective of this analysis is to explore the needs of informal ALS caregivers across the caregiving course.

Design

In an open-ended question as part of a semistructured interview, caregivers were asked what would help them in their role. Interviews took place on three occasions at 4-month to 6-month intervals. Demographic, burden and quality of life data were collected, in addition to the open-ended responses. We carried out descriptive statistical analysis and thematic analysis of qualitative data.

Setting and participants

Home interviews at baseline (n=81) and on two further occasions (n=56, n=41) with informal caregivers of people with ALS attending the National ALS/MND Clinic at Beaumont Hospital, Dublin, Ireland.

Results

The majority of caregivers were family members. Hours of care provided and caregiver burden increased across the interview series. Thematic analysis identified what would help them in their role, and needs related to external support and services, psychological-emotional factors, patient-related behaviours, a cure and 'nothing'. Themes were interconnected and their prevalence varied across the interview time points.

Conclusion

This study has shown the consistency and adaptation in what caregivers identified as helpful in their role, across 12–18 months of a caregiving journey. Support needs are clearly defined, and change with time and the course of caregiving. Caregivers need support from family, friends and healthcare professionals in managing their tasks and the emotional demands of caregiving. Identifying the specific needs of informal caregivers should enable health professionals to provide tailored supportive interventions.



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Correction: Electrosclerotherapy for capillary malformations: study protocol for a randomised within-patient controlled pilot trial

Horbach SER, Wolkerstorfer A, de Bruin DM, et al. Electrosclerotherapy for capillary malformations: study protocol for a randomised within-patient controlled pilot trial. BMJ Open 2017;7:e016401. doi: 10.1136/bmjopen-2017-016401

'Sanne M Jansen' was missed off the original author list. The correct author list and affiliations should read:

Sophie E R Horbach,1 Albert Wolkerstorfer,2 Daniel Martijn de Bruin,3 Sanne M Jansen,3 Chantal M A M van der Horst1

Department of Plastic, Reconstructive and Hand Surgery, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Noord-Holland, Netherlands

Department of Dermatology, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Noord-Holland, Netherlands

Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Amsterdam, Noord-Holland, Netherlands



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Trends and determinants of length of stay and hospital reimbursement following knee and hip replacement: evidence from linked primary care and NHS hospital records from 1997 to 2014

Objectives

To measure changes in length of stay following total knee and hip replacement (TKR and THR) between 1997 and 2014 and estimate the impact on hospital reimbursement, all else being equal. Further, to assess the degree to which observed trends can be explained by improved efficiency or changes in patient profiles.

Design

Cross-sectional study using routinely collected data.

Setting

National Health Service primary care records from 1995 to 2014 in the Clinical Practice Research Datalink were linked to hospital inpatient data from 1997 to 2014 in Hospital Episode Statistics Admitted Patient Care.

Participants

Study participants had a diagnosis of osteoarthritis or rheumatoid arthritis.

Interventions

Primary TKR, primary THR, revision TKR and revision THR.

Primary outcome measures

Length of stay and hospital reimbursement.

Results

10 260 primary TKR, 10 961 primary THR, 505 revision TKR and 633 revision THR were included. Expected length of stay fell from 16.0 days (95% CI 14.9 to 17.2) in 1997 to 5.4 (5.2 to 5.6) in 2014 for primary TKR and from 14.4 (13.7 to 15.0) to 5.6 (5.4 to 5.8) for primary THR, leading to savings of £1537 and £1412, respectively. Length of stay fell from 29.8 (17.5 to 50.5) to 11.0 (8.3 to 14.6) for revision TKR and from 18.3 (11.6 to 28.9) to 12.5 (9.3 to 16.8) for revision THR, but no significant reduction in reimbursement was estimated. The estimated effect of year of surgery remained similar when patient characteristics were included.

Conclusions

Length of stay for joint replacement fell substantially from 1997 to 2014. These reductions have translated into substantial savings. While patient characteristics affect length of stay and reimbursement, patient profiles have remained broadly stable over time. The observed reductions appear to be mostly explained by improved efficiency.



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TEXT messages to improve MEDication adherence and Secondary prevention (TEXTMEDS) after acute coronary syndrome: a randomised clinical trial protocol

Background

Identifying simple, low-cost and scalable means of supporting lifestyle change and medication adherence for patients following a cardiovascular (CV) event is important.

Objective

The TEXTMEDS (TEXT messages to improve MEDication adherence and Secondary prevention) study aims to investigate whether a cardiac education and support programme sent via mobile phone text message improves medication adherence and risk factor levels in patients following an acute coronary syndrome (ACS).

Study design

A single-blind, multicentre, randomised clinical trial of 1400 patients after an ACS with 12 months follow-up. The intervention group will receive multiple weekly text messages that provide information, motivation, support to adhere to medications, quit smoking (if relevant) and recommendations for healthy diet and exercise. The primary endpoint is the percentage of patients who are adherent to cardioprotective medications and the key secondary outcomes are mean systolic blood pressure (BP) and low-density lipoprotein cholesterol. Secondary outcomes will also include total cholesterol, mean diastolic BP, the percentage of participants who are adherent to each cardioprotective medication class, the percentage of participants who achieve target levels of CV risk factors, major vascular events, hospital readmissions and all-cause mortality. The study will be augmented by formal economic and process evaluations to assess acceptability, utility and cost-effectiveness.

Summary

The study will provide multicentre randomised trial evidence of the effects of a text message-based programme on cardioprotective medication adherence and levels of CV risk factors.

Ethics and dissemination

Primary ethics approval was received from Western Sydney Local Health District Human Research Ethics Committee (HREC2012/12/4.1 (3648) AU RED HREC/13/WMEAD/15). Results will be disseminated via peer-reviewed publications and presentations at international conferences.

Trial registration number

ACTRN12613000793718; Pre-results.



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CARE CR-Cardiovascular and cardiorespiratory Adaptations to Routine Exercise-based Cardiac Rehabilitation: a study protocol for a community-based controlled study with criterion methods

Introduction

Cardiac rehabilitation (CR) reduces all-cause and cardiovascular mortality in patients with coronary heart disease (CHD). Much of this improvement has been attributed to the beneficial effects of structured exercise training. However, UK-based studies have not confirmed this. Improvements in survival and cardiovascular health are associated with concurrent improvements in cardiorespiratory fitness (CRF). It is therefore concerning that estimated CRF improvements resulting from UK-based CR are approximately one-third of those reported in international literature. Modest improvements in CRF suggest that UK CR exercise training programmes may require optimisation if long-term survival is to be improved. However, contemporary UK studies lack control data or use estimates of CRF change. Cardiovascular and cardiorespiratory Adaptations to Routine Exercise-based CR is a longitudinal, observational, controlled study designed to assess the short-term and long-term effect of CR on CRF, as well cardiovascular and cardiometabolic health.

Methods and analysis

Patients will be recruited following referral to their local CR programme and will either participate in a routine, low-to-moderate intensity, 8-week (16 sessions) exercise-based CR programme or freely abstain from supervised exercise. Initial assessment will be conducted prior to exercise training, or approximately 2 weeks after referral to CR if exercise training is declined. Reassessment will coincide with completion of exercise training or 10 weeks after initial assessment for control participants. Participants will receive a final follow-up 12 months after recruitment. The primary outcome will be peak oxygen consumption determined using maximal cardiopulmonary exercise testing. Secondary outcomes will include changes in subclinical atherosclerosis (carotid intima–media thickness and plaque characteristics), body composition (dual X-ray absorptiometry) and cardiometabolic biomarkers.

Ethics and dissemination

Ethical approval for this non-randomised controlled study has been obtained from the Humber Bridge NHS Research Ethics Committee—Yorkshire and the Humber on the 27th September 2013, (12/YH/0278). Results will be presented at national conferences and published in peer-reviewed journals.



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Depressive symptoms and workplace-violence-related risk factors among otorhinolaryngology nurses and physicians in Northern China: a cross-sectional study

Objectives

Workplace violence is relatively frequent among medical professionals who work in otorhinolaryngology units. This phenomenon reduces the quality of provided medical care and increases the incidence of depressive symptoms among physicians and nurses, seriously affecting their job satisfaction and work efficiency with a negative attitude towards providing treatment. Few existing studies have assessed workplace-violence-related factors associated with depressive symptoms among otorhinolaryngology physicians and nurses.

Methods

We conducted a cross-sectional study in grade A tertiary hospitals of Heilongjiang province in Northern China, to evaluate the occurrence and level of depressive symptoms among otorhinolaryngology physicians and nurses and to analyse the relationship between them and workplace-violence-related risk factors and demographic variables.

Results

Of all our participating professionals, (379 otorhinolaryngologists and 273 nurses), 57.2% were found to have depressive symptoms, whereas, of the respondents who had suffered from physical violence, 71.25% had depressive symptoms. Professionals with less than 1 year of experience, as well as professionals who more frequently worked alone, were more likely to suffer from depressive symptoms than their colleagues.

Conclusions

This research addresses an emerging issue of clinical practice, and its results differ from those of previous studies; specifically, it indicates that the frequency of depressive symptoms among otorhinolaryngology physicians and nurses may be influenced by physical violence, the number of coworkers they have for more than half of their working hours and other workplace-violence-related factors. To reduce the depressive symptoms caused by workplace violence and improve the quality of medical services, medical institutions should implement effective measures to prevent the occurrence of physical violence, strengthen team cooperation ability and increase peer support.



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Measurement properties of instruments assessing permanent functional impairment of the spine: a systematic review protocol

Introduction

Permanent functional impairment (PFI) of the spine is a rating system used by compensation authorities, such as workers compensation boards, to establish an appropriate level of financial compensation for persistent loss of function. Determination of PFI of the spine is commonly based on the assessment of spinal movement combined with other measures of physical and functional impairments; however, the reliability and validity of the measurement instruments used for these evaluations have yet to be established. The aim of this study is to systematically review and synthesise the literature concerning measurement properties of the various and different instruments used for assessing PFI of the spine.

Methods

Three conceptual groups of terms (1) PFI, (2) spinal disorder and (3) measurement properties will be combined to search Medline, EMBASE, CINAHL, Web of Science, Scopus, PEDro, OTSeeker and Health and Safety Science Abstracts. We will examine peer-reviewed, full-text articles over the full available date range. Two reviewers will independently screen citations (title, abstract and full text) and perform data extraction. Included studies will be appraised as to their methodological quality using the COnsensus-based Standards for the selection of health Measurement INstruments criteria. Findings will be summarised and presented descriptively, with meta-analysis pursued as appropriate.

Ethics and dissemination

This review will summarise the current level of evidence of measurement properties of instruments used for assessing PFI of the spine. Findings of this review may be applicable to clinicians, policy-makers, workers' compensation boards, other insurers and health and safety organisations. The findings will likely provide a foundation and direction for future research priorities for assessing spinal PFI.

PROSPERO registration number

CRD42017060390.



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Blood-based biomarkers of cancer-related cognitive impairment in non-central nervous system cancer: protocol for a scoping review

Introduction

Cancer-related cognitive impairment (CRCI) can have detrimental effects on quality of life, even among patients with non-central nervous system (CNS) cancers. Several studies have been conducted to explore different markers associated with CRCI to understand its pathobiology. It is proposed that the underlying mechanisms of CRCI are related to a cascade of physiological adaptive events in response to cancer and/or treatment. Hence, peripheral blood would be a logical source to observe and identify these physiological events. This paper outlines the protocol for a scoping review being conducted to summarise the extant literature regarding blood-based biomarkers of CRCI among patients with non-CNS cancer.

Methods/analysis

Methods will be informed by the updated guidelines of Arksey and O'Malley. The systematic search for literature will include electronic databases, handsearching of key journals and reference lists, forward citation tracking and consultation with content experts. Study selection will be confirmed by duplicate review and calculation of inter-rater reliability. Data to be charted will include study design, sample size, cancer and treatment characteristics, demographic characteristics, cognitive variable/s and biomarkers assessed, associations between cognitive functioning and biomarkers (including statistics used), and rigour in biomarker sample collection and processing. Results will be presented through: (1) a descriptive numerical summary of studies, including a flow diagram based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, (2) a list of blood-based biomarkers associated with CRCI and (3) a narrative overview developed through collaboration among the research team and consultation with content experts.

Dissemination

The findings of this review will highlight current directions and gaps in the current body of evidence that may lead to improved rigour in future CRCI investigations. The dissemination of this work will be facilitated through the involvement of clinicians and researchers on the research team, an external consultation process and the presentation of the results through scholarly publication and presentation.



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Multiple types of human papillomavirus infection and anal precancerous lesions in HIV-infected men in Taiwan: a cross-sectional study

Objectives

This study aimed to assess the relationship between infection with multiple human papillomavirus (HPV) types and abnormal anal cytology in HIV-infected men.

Design

An observational, cross-sectional study.

Setting

A regional referral hospital in Taiwan.

Participants

In total, 714 HIV-infected men were enrolled between March 2011 and June 2016. Thin preparation anal Pap smears were interpreted according to the 2001 Bethesda System. Thirty-seven types of HPV were detected by reverse line blotting, including 13 oncogenic types and 24 non-oncogenic types.

Outcome measures

The relationship between anal HPV infection and abnormal anal cytology in people of Asian ethnicity and the coverage efficacy in HPV-vaccinated HIV-infected men.

Results

On anal cytology, 175 (24.5%) subjects had atypical squamous cells of undetermined significance (ASCUS) or higher grades of dysplasia, including 87 (49.7%) with ASCUS, 73 (41.7%) with low-grade squamous intraepithelial lesions (LSILs) and 15 (8.6%) with high-grade squamous intraepithelial lesions (HSILs). A higher proportion of subjects with those without LSIL/HSIL (93.1% vs 67.3%, P<0.0001) had multiple HPV types. The odds of having LSIL/HSIL increased with an increasing number of HPV types: the ORs ranged from 1 for no HPV types to 6.96 (95% CI 2.38 to 20.37) for more than five types (Ptrend <0.0001). Multivariate logistic regression analysis showed a significant association between LSIL/HSIL and the number of HPV genotypes present (OR 1.20; 95% CI 1.02 to 1.42, P<0.05). HPV types covered by the nonavalent HPV vaccine (types 6/11/16/18/31/33/45/52/58) were detected in 70.1% of the patients in this study.

Conclusions

The odds of having anal LSIL/HSIL are approximately seventimes greater in HIV-infected men with than withoutsix or more types of HPV. Multiple HPV types in HIV-infected patients deserves aggressive follow-up, and HPV vaccination programme require scaling up.



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Spread of carbapenem resistant Enterobacteriaceae at tertiary care cancer hospital in Egypt

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Evaluation of olive pomace in the production of novel broilers with enhanced in vitro antithrombotic properties

Abstract

Several attempts have been made not only to improve nutritional value of broilers but also to attenuate dependence on raw materials such as corn in compounded broilers feed. Therefore the aim of this study was to evaluate the impact of diets enriched with olive pomace (OP) on Ross 308 broilers growth performance, sensory characteristics and nutritional value in terms of cardioprotection. Broilers were fed four experimental diets containing 0 % OP (control group), 2.5 % OP (group A), 5.0 % OP (group B) and 7.5 % OP (group C). The obtained broiler meat samples were evaluated for their lipid and phenol content and their in vitro antithrombotic properties according to biological assay in human platelets. Groups B and C exhibited significantly increased (P < 0.05) growth rate compared to the ones of control group. Additionally group B exhibited significantly more potent (P < 0.05) in vitro antithrombotic properties (EC50 = 10.5±0.92) compared to the ones of control group (EC50 = 420±21.3). Grilled broiler meat of group B was found to have acceptable sensory properties. The overal conclusion of this paper is the potential use of OP in compounded broilers feed in the production of functional broilers meat.

Practical applications: The objective of this research is to assess the use of olive industry by-products as functional feed ingredients. For this purpose, broilers were fed experimental diets containing olive pomace (OP). Our results suggest that OP can be used in broiler feed to produce functional broilers meat with increased in vitro antithrombotic properties. These scientific data could have considerable practical value towards the valorisation of OP and increasing the sustainable production of functional broiler meat and therefore the overall food security.



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Solid fat content determination of dispersed lipids by time-domain NMR

Abstract

Time domain nuclear magnetic resonance (TD-NMR) was used to determine the solid fat content (SFC) of dispersions stabilized by a high molecular weight hydrocolloid (gum arabic, GA) containing a high melting lipid (tristearin, SSS). Since the lipid was molten prior to homogenization for the preparation of the dispersion it recrystallizes during cooling and storage. It is known that the recrystallization in a disperse system differs from bulk lipids and TD-NMR could be a helpful tool to investigate the phenomenon. SFC measurement by TD-NMR is well established and widely used in food science for oils, spreads and seeds. In the case of dispersions, however, the situation is more demanding due to the quasi-continuous phase. A suitable TD-NMR method has to account for that and can be realized when combining longitudinal and transverse relaxation properties to separate the signal contribution of the quasi-continuous phase and the solid lipid and liquid lipid dispersed phase. Signal from water and emulsifier was eliminated by magnetization inversion with an initial 180° pulse and a subsequent dedicated inversion delay. The emulsifier showed a longitudinal relaxation similar to the aqueous phase. With a carefully chosen inversion delay, both signal contributions of water and emulsifier could be suppressed, and a quantitative determination of the SFC was possible via dedicated data processing.

Practical applications: The method can be applied in characterization, stability tests and quality control of complex food emulsions and solid lipid particles, which are recently under development as drug carrier systems.



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Obesity and male infertility: role of fatty acids in the modulation of sperm energetic metabolism

Abstract

Obesity in men of reproductive age is increasing worldwide, impacting negatively on reproductive potential, sperm function and assisted reproduction outcomes. Changes in modern eating behaviors are needed to invert the negative correlation between lifestyle and sperm quality.

It is known from the literature that fatty acids are able to modulate lipid metabolism by complex mechanisms involving a sequence of interdependent and cross-regulated molecular events.

Although a great deal of data is currently available on the dietary modulation of lipid metabolism, little is known about the nutritional regulation of sperm energetic metabolism. In this review, major data from the literature about the role of some dietary fats as modulators of sperm function and quality are described. Moreover, biochemical mechanisms responsible for an impairment or improvement in sperm bioenergetics are critically analyzed.

It is noteworthy that both quantitative and qualitative aspects of dietary fats influence sperm function. The administration of a high-fat diet, low in polyunsaturated fatty acids, caused a significant increase in body weight hyperglycemia, hyperinsulinemia and dyslipidemia, along with a significant reduction in sperm quality. In contrast, unsaturated fatty acids are able to positively influence sperm quality and function.

The understanding of the biochemical mechanisms underlying the development of male infertility related to obesity led us to depict a possible framework for the molecular action of fatty acids on sperm quality during dysmetabolic conditions.

Practical applications: In this review major data from the literature about the spermatozoa targeting of dietary fatty acids are described and critically analyzed, because now dietary fatty acids are the current focus of research in the field of nutrition and reproduction in males. Such knowledge will eventually translate into the development of new attractive therapeutic approaches for male infertility related to alterations in lipid metabolism.



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Practical Management of Toxicities Associated With Bosutinib in Patients With Philadelphia Chromosome–Positive Chronic Myeloid Leukemia

Abstract
Bosutinib (SKI-606) is an oral, dual Src/Abl tyrosine kinase inhibitor (TKI) approved for treatment of patients with Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) that is resistant or intolerant to prior TKI therapy or for whom other TKIs are not appropriate choices. The objective of this review is to provide a longitudinal summary of toxicities that may arise during treatment with second-line or later bosutinib in patients with Ph+ chronic phase CML and to provide strategies for managing these toxicities. As bosutinib is not currently indicated for newly diagnosed CML, toxicities associated with first-line treatment are not reviewed. Recognition and optimal management of these toxicities can facilitate patient compliance and affect treatment outcomes.

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Neutrophil-to-lymphocyte ratio predicts anastomotic dehiscence

Background

Anastomotic dehiscence (AD) is the most feared complication following colonic and rectal anastomosis. Multiple attempts have been made to correlate the levels of biomarkers to the risk of AD. This study attempts to compare C-reactive protein (CRP), procalcitonin (PCT) and neutrophil-to-lymphocyte ratio (NLR) as predictors of AD.

Method

This case-controlled study collected data on patients undergoing colonic and rectal anastomosis over an 18-month period. Levels of CRP, PCT and NLR were recorded daily for the first 5 days post-operatively. These results were then compared between those who developed AD and those who did not.

Results

A total of 136 patients were included; 11 (8.1%) patients developed AD. CRP and NLR were useful predictors of AD with an area under the curve of 0.81 and 0.78 on post-operative day 4. PCT was not found to be raised significantly higher in patients who developed AD compared to those who did not.

Conclusion

CRP and NLR are useful predictors of AD. PCT is not a useful predictor of AD.



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Comparison of corneal biomechanics after myopic small-incision lenticule extraction compared to LASIK: an ex vivo study

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Cancers, Vol. 10, Pages 35: Reviewing the Utility of EUS FNA to Advance Precision Medicine in Pancreatic Cancer

Cancers, Vol. 10, Pages 35: Reviewing the Utility of EUS FNA to Advance Precision Medicine in Pancreatic Cancer

Cancers doi: 10.3390/cancers10020035

Authors: William Berry Joanne Lundy Daniel Croagh Brendan Jenkins

Advanced pancreatic cancer (PC) is an aggressive malignancy with few effective therapeutic options. While the evolution of precision medicine in recent decades has changed the treatment landscape in many cancers, at present no targeted therapies are used in the routine management of PC. Only a minority of patients with PC present with surgically resectable disease, and in the remainder obtaining high quality biopsy material for both diagnosis and molecular testing can prove challenging. Endoscopic ultrasound-guided fine needle aspiration (EUS FNA) is a widely used diagnostic procedure in PC, and allows tumour sampling in patients with both early and late stage disease. This review will provide an update on the role of EUS FNA as a diagnostic tool, as well as a source of genetic material which can be used both for molecular analysis and for the creation of valuable preclinical disease models. We will also consider relevant clinical applications of EUS FNA in the management of PC, and the path towards bringing precision medicine closer to the clinic in this challenging disease.



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Cancers, Vol. 10, Pages 34: Extracellular Influences: Molecular Subclasses and the Microenvironment in Pancreatic Cancer

Cancers, Vol. 10, Pages 34: Extracellular Influences: Molecular Subclasses and the Microenvironment in Pancreatic Cancer

Cancers doi: 10.3390/cancers10020034

Authors: Veronique Veenstra Andrea Garcia-Garijo Hanneke van Laarhoven Maarten Bijlsma

Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent form of pancreatic cancer and carries the worst prognosis of all common cancers. Five-year survival rates have not surpassed 6% for some decades and this lack of improvement in outcome urges a better understanding of the PDAC-specific features which contribute to this poor result. One of the most defining features of PDAC known to contribute to its progression is the abundance of non-tumor cells and material collectively known as the stroma. It is now well recognized that the different non-cancer cell types, signalling molecules, and mechanical properties within a tumor can have both tumor-promoting as well as –inhibitory effects. However, the net effect of this intratumour heterogeneity is not well understood. Heterogeneity in the stromal makeup between patients is even less well established. Such intertumour heterogeneity is likely to be affected by the relative contributions of individual stromal constituents, but how these contributions exactly relate to existing classifications that demarcate intertumour heterogeneity in PDAC is not fully known. In this review, we give an overview of the available evidence by delineating the elements of the PDAC stroma and their contribution to tumour growth. We do so by interpreting the heterogeneity at the gene expression level in PDAC, and how stromal elements contribute to, or interconnect, with this.



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Twitter Use in the Hematopoietic Cell Transplantation Community

Abstract

Purpose of Review

Social media has revolutionized the access and exchange of information in healthcare. The microblogging platform Twitter has been used by blood and marrow transplant physicians over the last several years with increasing enthusiasm. We review the adoption of Twitter in the transplant community and its implications on clinical care, education, and research.

Recent Findings

Twitter allows instantaneous access to the latest research publications, developments at national and international meetings, networking with colleagues, participation in advocacy, and promoting available clinical trials. Additionally, Twitter serves as a gateway for resources dedicated to education and support for patients undergoing transplantation.

Summary

We demonstrate the utilization and various applications in using Twitter among hematopoietic cell transplant healthcare professionals, patients, and other affiliated stakeholders. Professionalism concerns with clinician use of such social media platforms, however, also exist. Overall, Twitter has enhanced and increased the opportunities for engagement in the transplant community.



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Rethinking Antimicrobial Prophylaxis in the Transplant Patient in the World of Emerging Resistant Organisms—Where Are We Today?

Abstract

Purpose of Review

The use of prophylactic antibiotics during the neutropenic period in hematopoietic stem cell transplantation has been the standard of care at most institutions for the past 20 years. We sought to review the benefits and risks of this practice.

Recent Findings

Emerging data has highlighted the potential costs of antibacterial prophylaxis, from selecting for antibiotic resistance to perturbing the microbiome and contributing to increase risk for Clostridium difficile and perhaps graft-versus-host-disease, conditions which may lead to poorer outcomes.

Summary

Though in many studies prophylactic antibiotics improved morbidity and mortality outcomes, the potential harms including antibiotic resistance, Clostridium difficile infection, and alterations of the gut microbiome should be considered. Future studies aimed to better risk-stratify patients and limit the use of broad-spectrum antibiotics are warranted.



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