Αρχειοθήκη ιστολογίου

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Κυριακή 21 Ιανουαρίου 2018

Encoding, Reading, and Transforming Information Using Multifluorescent Supramolecular Polymeric Hydrogels

Abstract

Traditional (1D, 2D, and 3D) codes are widely used to provide convenient readouts of encoded information. However, manipulating and transforming the encoded information is typically difficult to achieve. Here, the preparation of three fluorescent (blue, green, and red) hydrogels containing both tetracationic receptor–anion recognition motifs and gel-specific fluorophores is reported, which may be used as building blocks to construct through physical adhesion fluorescent color 3D codes (Code A, Code B, and Code C) that may be read out by a smartphone. As a result, parts of the individual gel components that make up Code B can be replaced with other gel building blocks to form Code A via a cut and adhesion approach. A fluorophore responsive to ammonia is further incorporated into one of the hydrogels. This allows the gel block-derived pattern that makes up Code C to be converted to Code A by chemical means. Therefore, the encoded information produced by patterns of the present hydrogels may be transformed through either physical action or by exposure to a chemical stimulus. Due to the nature of the soft materials involved, the codes can be used as wearable materials.

Thumbnail image of graphical abstract

The encoded information produced by patterns of three fluorescent (blue, green, and red) hydrogels can be transformed through either physical action (cut and reheal) or by exposure to a chemical stimulus (i.e., ammonia). Due to the nature of the soft materials involved, the codes can be used as wearable materials.



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Alternatives to animal testing in basic and preclinical research of atopic dermatitis

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease of increasing prevalence, especially in industrialized countries. Roughly 25% of the children and 1-3% of adults are affected. Although significant progress has been made in the understanding of the pathogenesis of AD, many aspects remain poorly understood. Moreover, there is a pressing need for improved therapeutic options. Studies to elucidate the pathophysiological pathways of AD and to identify novel therapeutic targets over the last few decades have been conducted almost exclusively in animal models. However, in vitro approaches such as 3D skin disease models have recently emerged due to an increasing awareness of distinct inter-species related differences that hamper the effective translation of results from animal models to humans. In addition, there is growing political and social pressure to develop alternatives to animal models according to the 3Rs principle (reduction, refinement and replacement of animal models). In this review, we briefly summarize commonly used animal models of AD and discuss the advancements and limitations of human-based in vitro models in AD research. Moreover, we address aspects where further improvements are urgently required.

This article is protected by copyright. All rights reserved.



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Improvement of diagnostic performance of pathologists by reducing the number of pathologists responsible for thyroid fine needle aspiration cytology: An institutional experience

Background

Various efforts have been made to improve the diagnostic accuracy of thyroid fine needle aspiration (FNA) cytology. We changed the diagnostic system by reducing the number of pathologists responsible for the thyroid FNA cytology in the routine work, and analyzed the effect on the pathologist's diagnostic performance.

Methods

Since March 1, 2015, 3 pathologists have been responsible for diagnostic thyroid FNA, previously undertaken by 9 equally. We compared the prechange period (three months, 319 nodules) and the postchange period (12 months, 1194 nodules).

Results

The turnaround time was shortened from 1.4 ± 0.7 days to 0.9 ± 0.5 days (P < .001). The utilization rate of the Bethesda system for Reporting Thyroid Cytopathology (TBSRTC) increased from 92.5% to 99.8%. Diagnostic rates of categories that are confirmative [II (benign) and VI (malignant)] increased, while the inadequate (I) or indeterminate (III) categories decreased. With category IV (follicular neoplasm), a challenging category in our country, an elevated malignancy rate was found at follow-up. Overall, the diagnostic performance was improved in terms of sensitivity (from 98.5% to 99.2%) and specificity (from 94.4% to 98.4%), with reduced false-negative rates (from 1.5% to 0.8%) and false-positive rates (from 2.9% to 1.1%). The area under the receiver operating characteristic curve increased from 0.861 to 0.958.

Conclusion

Reducing the number of pathologists responsible for diagnostic thyroid FNA cytology resulted in a higher utilization rate of TBSRTC, and more rapid and accurate diagnosis.



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Colorectal Cancer (CRC) Monitoring by Six-Monthly 18FDG-PET/CT: An Open-Label Multicentre Randomised Trial

Abstract
Background
18FDG-PET/CT has high sensitivity for detecting recurrences of colorectal cancer (CRC). Our objective was to determine whether adding routine 6-monthly 18FDG-PET/CT to our usual monitoring strategy improved patient outcomes and to assess the effect on costs.
Patients and Methods
In this open-label multicentre trial, patients in remission of CRC (stage II perforated, stage III, or stage IV) after curative surgery were randomly assigned (1:1) to usual monitoring alone (3-monthly physical and tumour marker assays, 6-monthly liver ultrasound and chest radiograph, and 6-monthly whole-body computed tomography) or with 6-monthly 18FDG-PET/CT, for 3 years. A multidisciplinary committee reviewed each patient's data every 3 months and classified the recurrence status as yes/no/doubtful. Recurrences were treated with curative surgery alone if feasible and with chemotherapy otherwise. The primary endpoint was treatment failure defined as unresectable recurrence or death. Relative risks (RR) were estimated, and survival was analysed using the Kaplan-Meier method, Log-Rank test, and Cox models. Direct costs were compared.
Results
Of the 239 enrolled patients, 120 were in the intervention arm and 119 in the control arm. The failure rate was 29.2% (31 unresectable recurrences and 4 deaths) in the intervention group and 23.7% (27 unresectable recurrences and 1 death), in the control group (RR = 1.23; 95%CI, 0.80-1.88; p=0.34). The multivariate analysis also showed no significant difference (hazards ratio, 1.33; 95%CI, 0.8-2.19; p=0.27). Median time to diagnosis of unresectable recurrence (months) was significantly shorter in the intervention group (7 [3-20] vs. (14.3 [7.3-27], p=0.016). Mean cost/patient was higher in the intervention group (18 192±27 679 €vs. 11 131±13 254 €, p<0.033).
Conclusion
18FDG-PET/CT, when added every six months, increased costs without decreasing treatment failure rates in patients in remission of CRC. The control group had very close follow-up, and any additional improvement (if present) would be small and hard to detect.
ClinicalTrials.gov identifier
NCT00624260

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Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis

Abstract
Background
Recent efforts of genome-wide gene expression profiling analyses have improved our understanding of the biological complexity and diversity of triple negative breast cancers (TNBCs) reporting, at least 6 different molecular subtypes of TNBC namely Basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL) and luminal androgen receptor (LAR). However, little is known regarding the potential driving molecular events within each subtype, their difference in survival and response to therapy. Further insight into the underlying genomic alterations is therefore needed.
Patients and Methods
This study was performed using copy-number aberrations, somatic mutations and gene expression data derived from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA). TNBC samples (n = 550) were classified according to Lehmann's molecular subtypes using the TNBCtype online subtyping tool (http://cbc.mc.vanderbilt.edu/tnbc/).
Results
Each subtype showed significant clinic-pathological characteristic differences. Using a multivariate model, IM subtype showed to be associated with a better prognosis (HR = 0.68; CI = 0.46-0.99; p = 0.043) whereas LAR subtype was associated with a worst prognosis (HR = 1.47; CI = 1.0-2.14; p = 0.046). BL1 subtype was found to be most genomically instable subtype with high TP53 mutation (92%) and copy-number deletion in genes involved in DNA repair mechanism (BRCA2, MDM2, PTEN, RB1 & TP53). LAR tumours were associated with higher mutational burden with significantly enriched mutations in PI3KCA (55%), AKT1 (13%) and CDH1 (13%) genes. M and MSL subtypes were associated with higher signature score for angiogenesis. Finally, IM showed high expression levels of immune signatures and check-point inhibitor genes such as PD1, PDL1 and CTLA4.
Conclusion
Our findings highlight for the first time the substantial genomic heterogeneity that characterize TNBC molecular subtypes, allowing for a better understanding of the disease biology as well as the identification of several candidate targets paving novel approaches for the development of anti-cancer therapeutics for TNBC.

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Next generation immunotherapies for lymphoma: one foot in the future

Abstract
Improved understanding of the interactions between cancer cells and the immune system combined with technological advances has led to the development of novel types of immunotherapies. These include checkpoint inhibitors (CPI), T cell engager antibodies (TCE), and Chimeric Antigen Receptor (CAR)-T cells which have demonstrated remarkable efficacy in B-cell malignancies, including anti-PD1 antibodies in Hodgkin lymphoma, and TCE and CAR-T cells in B-ALL, leading to their approval in these indications. Recent clinical data suggest that these immunotherapies may also benefit patients with other types of hematologic malignancies, particularly patients with Hodgkin and non-Hodgkin lymphomas. Here, we review the most recent clinical data regarding these different immunotherapies in patients with lymphoma. Ongoing and future studies should further define which immunotherapy may best apply to a given patient in order to provide a "personalized immunotherapy".

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Genetic Landscape of Ultra-Stable Chronic Lymphocytic Leukemia Patients

Abstract
Background
Chronic lymphocytic leukemia (CLL) has a heterogeneous clinical course. Beside patients requiring immediate treatment, others show an initial indolent phase followed by progression and others do not progress for decades. The latter two subgroups usually display mutated IGHV genes and a favorable FISH profile.
Patients and Methods
Patients with absence of disease progression for over 10 years (11-30) from diagnosis were defined as ultra-stable CLL (US-CLL). Forty US-CLL underwent extensive characterization including whole exome sequencing (WES), ultra-deep sequencing and copy number aberration (CNA) analysis to define their unexplored genomic landscape. Microarray analysis, comparing US-CLL with non US-CLL with similar immunogenetic features (mutated IGHV/favorable FISH), was also performed to recognize US-CLL at diagnosis.
Results
WES was carried out in 20 US-CLL and 84 non-silent somatic mutations in 78 genes were found. When re-tested in a validation cohort of 20 further US-CLL, no recurrent lesion was identified. No clonal mutations of NOTCH1, BIRC3, SF3B1 and TP53 were found, including ATM and other potential progression driving mutations. CNA analysis identified 31 lesions, none with known poor prognostic impact. No novel recurrent lesion was identified: most cases showed no lesions (38%) or an isolated del(13q) (31%). The expression of 6 genes, selected from a gene expression profile analysis by microarray and quantified by droplet digital PCR on a cohort of 79 CLL (58 US-CLL and 21 non US-CLL), allowed to build a decision-tree capable of recognizing at diagnosis US-CLL patients.
Conclusions
The genetic landscape of US-CLL is characterized by the absence of known unfavorable driver mutations/CNA and of novel recurrent genetic lesions. Among CLL patients with favorable immunogenetics, a decision-tree based on the expression of 6 genes may identify at diagnosis patients who are likely to maintain an indolent disease for decades.

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Cultural competency and culturally safe clinical care [Letters]



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New hope for unsanctioned safe injection site [News]



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Effect of provincial spending on social services and health care on health outcomes in Canada: an observational longitudinal study [Research]

BACKGROUND:

Escalating health care spending is a concern in Western countries, given the lack of evidence of a direct connection between spending and improvements in health. We aimed to determine the association between spending on health care and social programs and health outcomes in Canada.

METHODS:

We used retrospective data from Canadian provincial expenditure reports, for the period 1981 to 2011, to model the effects of social and health spending (as a ratio, social/health) on potentially avoidable mortality, infant mortality and life expectancy. We used linear regressions, accounting for provincial fixed effects and time, and controlling for confounding variables at the provincial level.

RESULTS:

A 1-cent increase in social spending per dollar spent on health was associated with a 0.1% (95% confidence interval [CI] 0.04% to 0.16%) decrease in potentially avoidable mortality and a 0.01% (95% CI 0.01% to 0.02%) increase in life expectancy. The ratio had a statistically nonsignificant relationship with infant mortality (p = 0.2).

INTERPRETATION:

Population-level health outcomes could benefit from a reallocation of government dollars from health to social spending, even if total government spending were left unchanged. This result is consistent with other findings from Canada and the United States.



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Growing consensus on link between strep and obsessive-compulsive disorder [News]



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Management of osteoarthritis of the knee in younger patients [Review]



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The need for health in all policies in Canada [Commentary]



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Hoarseness of unclear origin in adults [Practice]



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Not all Polysporin products contain lidocaine [Letters]



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Muscle weakness related to herpes zoster [Practice]



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Blood-delivering drones saving lives in Africa and maybe soon in Canada [News]



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Parentheses [Humanities]



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Reducing the cost of inequality [CODA]



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5-Chloro-2,4-dihydroxypyridine, CDHP, prevents lung metastasis of basal-like breast cancer cells by reducing nascent adhesion formation

Abstract

A drug for metastasis prevention is necessary. The orally administered anticancer drug S-1 contributes to cancer therapy. In a mouse xenograft model of metastatic breast cancer from our previous study, the administration of S-1 inhibited lung metastasis. However, the mechanism of inhibition remains elusive. S-1 contains 5-chloro-2,4-dihydroxypyridine (CDHP), which does not have the antigrowth activity, but prevents the degradation of 5-fluorouracil, an anticancer reagent. In this study, we found that CDHP treatment shrinks cell morphology in metastatic basal-like breast cancer cell lines. Wound healing assays showed reduced cell migration in CDHP-treated cells. At the molecular level, CDHP treatment reduced the number of nascent adhesions, whereas the number of mature focal adhesions was not changed. These findings indicate that CDHP impairs focal adhesion formation, which results in a reduction in cell migration. For the in vivo metastasis assay, we used a highly lung-metastatic cell line. We xenografted them into immunodeficient mice, and administered CDHP. To determine whether CDHP prevents metastasis, we measured the weights of harvested lungs. The results showed that the lung weights of the CDHP-treated animals were not significantly different compared to the no-tumor controls, whereas the vehicle group showed a number of metastatic foci and an increase in lung weight. These observations indicate that CDHP administration prevents metastasis. This study reveals a novel effect of CDHP for lung metastasis prevention. Our findings may facilitate the establishment of future metastasis prevention therapies.

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This study found a novel function of 5-chloro-2,4-dihydroxypyridine (CDHP), a component of the anti-cancer drug S-1, on cancer metastasis. CDHP-treated cells reduces cell migration and lung metastasis. Our findings may contribute to the development of metastasis prevention therapies.



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Spatial barriers impact upon appropriate delivery of radiotherapy in breast cancer patients

Abstract

Radiotherapy (RT) is the standard treatment for breast cancer patients after conserving surgery or mastectomy when patients are at high risk of relapse. Major obstacles to appropriate RT delivery are journey times. Since studies on access to RT were carried out mostly in large countries, this study investigated factors in an Italian region and the influence of RT delivery on survival. A total of 4735 female candidates for RT were included in the study. A geographic information system calculated journey times from patients' homes and surgery hospitals to RT centers. Logistic regression analyzed the influence of journey times, socioeconomic status, and other factors on RT delivery. Survival probabilities and excess mortality were assessed in 4364 propensity score-matched patients. Journey times of 40 min or less from residence and from surgery hospital to RT center played a major role in access to RT. A large survival difference emerged between treated and untreated breast cancer patients. The excess mortality for untreated patients compared with propensity score-matched women receiving RT was 3.1 (95% CI: 2.2–4.3). Expansion of RT facilities during the 11-year study period improved RT delivery and outcomes by increasing availability but mainly by shortening journey times.

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This is the first European study to investigate the impact of spatial barriers upon appropriate radiotherapy (RT) in breast cancer patients. In Umbria, central Italy, journey times >40 min significantly decreased the probability of receiving RT and were consequently associated with poor outcome. New RT centers provided more patients with appropriate treatment, raising the issue of a "hub and spoke" approach. Spatial barriers to RT in Europe deserve investigation.



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SALL4 - KHDRBS3 network enhances stemness by modulating CD44 splicing in basal-like breast cancer

Abstract

Understanding the mechanism by which cancer cells enhance stemness facilitates cancer therapies. Here, we revealed that a stem cell transcription factor, SALL4, functions to enhance stemness in basal-like breast cancer cells. We used shRNA-mediated knockdown and gene overexpression systems to analyze gene functions. To evaluate stemness, we performed a sphere formation assay. In SALL4 knockdown cells, the sphere formation ability was reduced, indicating that SALL4 enhances stemness. CD44 is a membrane protein and is known as a stemness factor in cancer. CD44 splicing variants are involved in cancer stemness. We discovered that SALL4 modulates CD44 alternative splicing through the upregulation of KHDRBS3, a splicing factor for CD44. We cloned the KHDRBS3-regulated CD44 splicing isoform (CD44v), which lacks exons 8 and 9. CD44v overexpression prevented a reduction in the sphere formation ability by KHDRBS3 knockdown, indicating that CD44v is positively involved in cancer stemness. In addition, CD44v enhanced anoikis resistance under the control of the SALL4 - KHDRBS3 network. Basal-like breast cancer is an aggressive subtype among breast cancers, and there is no effective therapy so far. Our findings provide molecular targets for basal-like breast cancer therapy. In the future, this study may contribute to the establishment of drugs targeting cancer stemness.

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This study revealed that the SALL4 - KHDRBS3 network augments stemness through modulation of CD44 splicing in basal-like breast cancer. This network enhances anoikis resistance for stemness. This study may contribute to the establishment of therapies targeting cancer stemness.



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Is there different risk of cancer among end-stage renal disease patients undergoing hemodialysis and peritoneal dialysis?

Abstract

Cancer is a global issue in recent decade. Despite this alarming increase in the incidence of cancer, to date, whether the risk of developing cancer differs among peritoneal dialysis (PD) and hemodialysis (HD) patients is still uncertain. In this retrospective cohort study, data were obtained from the National Health Insurance Research Database of Taiwan, which provides coverage to almost 99% of the nation's population. After matching, a total of 4491 (or 3369) incident PD patients and 8982 (or 6738) incident HD patients between 2000 and 2009 were enrolled from the database. In addition, 22,455 (or 16,845) nondialysis patients were selected as a control group. The patients were monitored for the occurrence of cancer until 2010, and their data were analyzed using several different models. In general, the results showed that the risks of hepatocellular, kidney, bladder, extra kidney/bladder urinary tract, and thyroid cancers were higher in dialysis patients. We also compared the risk of cancer between two dialysis groups by using the HD patients as the reference group. The result showed that there is no significant different for each cancer risk between two dialysis groups. In conclusion, dialysis patients had a higher risk of certain types of cancer than those in the nonuremia group. However, there was no significant difference in the cancer risk between the two dialysis groups when compared directly.

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Dialysis patients had a higher risk of some cancer while comparing to nonuremia group. But there is no significant different cancer risk between two dialysis groups if comparing these two groups directly.



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CTAPIII/CXCL7: a novel biomarker for early diagnosis of lung cancer

Abstract

It is desirable to have a biomarker which can facilitate low-dose CT in diagnosis of early stage lung cancer. CTAPIII/CXCL7 is reported to be a potential biomarker for diagnosis of early lung cancer. In this study, we investigated the serum level of CTAPIII/CXCL7 in patients at different stage of lung cancer and the diagnostic efficacy of CTAPIII/CXCL7 in NSCLC. The plasma level of CTAPIII/CXCL7 was assayed by ELISA. CEA, SCCAg, and Cyfra211 were measured using a commercial chemiluminescent microparticle immunoassay. A total of 419 subjects were recruited, including 265 NSCLC patients and 154 healthy individuals. The subjects were randomly assigned to a training set and a test set. Receiver operating characteristic (ROC) and binary logistic regression analyses were conducted to evaluate the diagnostic efficacy and establish diagnostic mathematical model. Plasma CTAPIII/CXCL7 levels were significantly higher in NSCLC patients than in controls, which was independent of the stage of NSCLC. The diagnostic efficiency of CTAPIII/CXCL7 in NSCLC (training set: area under ROC curve (AUC) 0.806, 95% CI: 0.748–0.863; test set: AUC 0.773, 95% CI: 0.711–0.835) was greater than that of SCCAg, Cyfra21-1, or CEA. The model combining CTAPIII/CXCL7 with CEA, SCCAg, and Cyfra21-1 was more effective for NSCLC diagnosis than CTAPIII/CXCL7 alone. In addition, plasma level of CTAPIII/CXCL7 may contribute to the early diagnosis of NSCLC. CTAPIII/CXCL7 can be used as a plasma biomarker for the diagnosis of NSCLCs, particularly early stage lung cancer, with relatively high sensitivity and specificity.



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Patterning of individual heterogeneity in body mass index: evidence from 57 low- and middle-income countries

Abstract

Modeling variation at population level has become increasingly valued, but no clear application exists for modeling differential variation in health between individuals within a given population. We applied Goldstein's method (in: Everrit, Howell (eds) Encyclopedia of statistics in behavioral science, Wiley, Hoboken, 2005) to model individual heterogeneity in body mass index (BMI) as a function of basic sociodemographic characteristics, each independently and jointly. Our analytic sample consisted of 643,315 non-pregnant women aged 15–49 years pooled from the latest Demographic Health Surveys (rounds V, VI, or VII; years 2005–2014) across 57 low- and middle-income countries. Individual variability in BMI ranged from 9.8 (95% CI: 9.8, 9.9) for the youngest to 23.2 (95% CI: 22.9, 23.5) for the oldest age group; 14.2 (95% CI: 14.1, 14.3) for those with no formal education to 19.7 (95% CI: 19.5, 19.9) for those who have completed higher education; and 13.6 (95% CI: 13.5, 13.7) for the poorest quintile to 20.1 (95% CI: 20.0, 20.2) for the wealthiest quintile group. Moreover, variability in BMI by age was also different for different socioeconomic groups. Empirically testing the fundamental assumption of constant variance and identifying groups with systematically large differentials in health experiences have important implications for reducing health disparity.



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Inner-city green space and its association with body mass index and prevalent type 2 diabetes: a cross-sectional study in an urban German city

Objective

The accessibility of green space is an important aspect of the urban residential environment and has been found to be beneficial for health and well-being. This study investigates the association between different indicators of green space and the outcomes body mass index (BMI) and prevalent type 2 diabetes in an urban population.

Design

Population-based cross-sectional study.

Setting

Dortmund, a city located in the industrial Ruhr area in Western Germany.

Participants

1312 participants aged 25–74 years from the Dortmund Health Study.

Methods

The participants' addresses were geocoded and shapefiles of statistical districts, road network and land use, as well as data on neighbourhood characteristics were obtained at baseline. Three indicators of green space were constructed using geographical information systems: proportion of green space, recreation location quotient (RLQ) weighted by population and distance to the next park or forest. Multilevel linear and logistic regression analyses on the association of green space with BMI and type 2 diabetes were performed, adjusted by individual-level characteristics and neighbourhood unemployment rate.

Results

The multilevel regression analyses showed no association between green space and BMI. In contrast, the three indicators of green space were significantly associated with type 2 diabetes. Residents of neighbourhoods with a low RLQ had a 2.44 (95% CI 1.01 to 5.93) times higher odds to have type 2 diabetes compared with residents of high RLQ neighbourhoods. Likewise, residing more than 0.8 km away from the nearest park or forest increased the odds of type 2 diabetes (OR 1.71, 95% CI 1.05 to 2.77).

Conclusions

This study indicates that green space and its spatial accessibility might play a role in the development of type 2 diabetes. Further research is needed to clarify this association.



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Engaging older people in an internet platform for cardiovascular risk self-management: a qualitative study among Dutch HATICE participants

Objectives

To study older peoples' experiences with an interactive internet platform for cardiovascular self-management, to assess which factors influence initial and sustained engagement. To assess their views on future use within primary care.

Design

Qualitative semistructured interview study, with thematic analysis.

Setting

Primary care in the Netherlands.

Participants

People ≥65 years with an increased risk of cardiovascular disease who used the 'Healthy Ageing Through Internet Counselling in the Elderly' internet platform with remote support of a coach. Participants were selected using a purposive sampling method based on gender, age, level of education, cardiovascular history, diabetes, duration of participation and login frequency.

Results

We performed 17 interviews with 20 participants, including three couples. In the initial phase, platform engagement was influenced by perceived computer literacy of the participants, user-friendliness, acceptability and appropriateness of the intervention and the initial interaction with the coach. Sustained platform use was mainly facilitated by a relationship of trust with the coach. Other facilitating factors were regular automatic and personal reminders, clear expectations of the platform, incorporation into daily routine, social support and a loyal and persistent attitude. Perceived lack of change in content of the platform could work both stimulating and discouraging. Participants supported the idea of embedding the platform into the primary care setting.

Conclusions

Human support is crucial to initial and sustained engagement of older people in using an interactive internet platform for cardiovascular self-management. Regular reminders further facilitate sustained use, and increased tailoring to personal preference is recommended. Embedding the platform in primary healthcare may enhance future adoption.

Trial registration number

ISRCTN48151589; Pre-results.



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Small cortical grey matter lesions show no persistent infarction in transient ischaemic attack? A prospective cohort study

Objectives

To find determining factors for persistent infarction signs in patients with transient ischaemic attack (TIA), herein initial diffusion lesion size, visibility on apparent diffusion coefficient (ADC) or fluid-attenuated inversion recovery (FLAIR) and location.

Design

Prospective cohort study of patients with clinical TIA receiving 3T-MRI within 72 hours of symptom onset and at 8-week follow-up.

Setting

Clinical workflow in a single tertiary stroke centre between February 2012 and June 2014.

Participants

199 candidate patients were recruited, 64 patients were excluded due to non-TIA discharge diagnosis or no 8-week MRI. 122 patients completed the study.

Primary outcome measures

The primary outcome was visible persistent infarction defined as 8-week FLAIR hyperintensity or atrophy corresponding to the initial diffusion-weighted imaging (DWI) lesion.

Results

50 patients showed 84 initial DWI lesions. 29 (35%) DWI lesions did not result in infarction signs on 8-week FLAIR. 26 (90%, P<0.0001) reversing lesions were located in the cortical grey matter (cGM). cGM location (vs any other location) strongly predicted no 8-week infarction sign development (OR 0.02, 95% CI 0.001 to 0.17) or partial lesion area decrease (>30% of initial DWI-area, OR 14.10, 95% CI 3.61 to 54.72), adjusted for FLAIR-visibility, DWI-area, ADC-confirmation and time to scan (TTS) from symptom onset to baseline MRI. Acute FLAIR-visibility was a strong associated factor for persistent infarction signs (OR 33.06, 95% CI 2.94 to 1432.34). For cGM lesions area size was sole associated factor for persistent infarction signs with a 0.31 cm2 (area under the curve (AUC), 0.97) threshold. In eight (16%) DWI-positive patients, all lesions reversed fully.

Conclusions

16% of DWI-positive patients and one-third of acute DWI lesions caused no persistent infarction signs, especially small cGM lesions were not followed by development of persistent infarction signs. Late MRI after TIA is likely to be less useful in the clinical setting, and it is dubious if the absence of old vascular lesions can be taken as evidence of no prior ischaemic attacks.

Trial registration number

NCT01531946; Results.



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Determinants of non-adherence to treatment for tuberculosis in high-income and middle-income settings: a systematic review protocol

Introduction

Treatment for tuberculosis (TB) is highly effective if taken according to prescribed schedules. However, many people have difficulty adhering to treatment which can lead to poorer clinical outcomes, the development of drug resistance, increased duration of infectivity and consequent onward transmission of infection. A range of approaches are available to support adherence but in order to target these effectively a better understanding of the predictors of poor adherence is needed. This review aims to highlight the personal, sociocultural and structural factors that may lead to poor adherence in high-income and middle-income settings.

Methods and analysis

Seven electronic databases, Medline, EMBASE, CINAHL, PsycInfo, The Cochrane Library, Scopus and Web of Science, will be searched for relevant articles using a prespecified search strategy. Observational studies will be targeted to explore factors that influence adherence to treatment in individuals diagnosed with TB. Screening title and abstract followed by full-text screening and critical appraisal will be conducted by two researchers. Data will be extracted using the Population, Exposure, Comparator, Outcomes, Study characteristics framework. For cross-study assessment of strength of evidence for particular risk factors affecting adherence we will use the Grading of Recommendations, Assessment, Development and Evaluation tool modified for prognostic studies. A narrative synthesis of the studies will be compiled. A meta-analysis will be considered if there are sufficient numbers of studies that are homogenous in study design, population and outcomes.

Dissemination

A draft conceptual framework will be identified that (A) identifies key barriers to adherence at each contextual level (eg, personal, sociocultural, health systems) and (B) maps the relationships, pathways and mechanisms of effect between these factors and adherence outcomes for people with TB. The draft conceptual framework will guide targeting of adherence interventions and further research.

PROSPERO registration number

CRD42017061049.



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The Suspected CANcer (SCAN) pathway: protocol for evaluating a new standard of care for patients with non-specific symptoms of cancer

Introduction

Cancer survival in England lags behind most European countries, due partly to lower rates of early stage diagnosis. We report the protocol for the evaluation of a multidisciplinary diagnostic centre-based pathway for the investigation of 'low-risk but not no-risk' cancer symptoms called the Suspected CANcer (SCAN) pathway. SCAN is a new standard of care being implemented in Oxfordshire; one of a number of pathways implemented during the second wave of the Accelerate, Coordinate, Evaluate (ACE) programme, an initiative which aims to improve England's cancer survival rates through establishing effective routes to early diagnosis.

Methods and analysis

To evaluate SCAN, we are collating a prospective database of patients referred onto the pathway by their general practitioner (GP). Patients aged over 40 years, with non-specific symptoms such as weight loss or fatigue, who do not meet urgent cancer referral criteria or for whom symptom causation remains unclear after investigation via other existing pathways, can be referred to SCAN. SCAN provides rapid CT scanning, laboratory testing and clinic review within 2 weeks. We will follow all patients in the primary and secondary care record for at least 2 years. The data will be used to understand the diagnostic yield of the SCAN pathway in the short term (28 days) and the long term (2 years). Routinely collected primary and secondary care data from patients not referred to SCAN but with similar symptoms will also be used to evaluate SCAN. We will map the routes to diagnosis for patients referred to SCAN to assess cost-effectiveness. Acceptability will be evaluated using patient and GP surveys.

Ethics and dissemination

The Oxford Joint Research Office Study Classification Group has judged this to be a service evaluation and so outside of research governance. The results of this project will be disseminated by peer-reviewed publication and presentation at conferences.



http://ift.tt/2mZqXX5

Comparative efficacy and acceptability of interventions for major depression in older persons: protocol for Bayesian network meta-analysis

Introduction

Major depression is a leading cause of disability and has been associated with adverse effects in older persons. While many pharmacological and non-pharmacological interventions have been shown to be effective to address major depression in older persons, there has not been a meta-analysis that consolidates all the available interventions and compare the relative benefits of these available interventions. In this study, we aim to conduct a systematic review and network meta-analysis to compare the efficacy and acceptability of all the known pharmacological and non-pharmacological interventions for major depression in older persons.

Methods and analysis

We will search Medline, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials and references of other review articles for articles related to the keywords of 'randomised trial', 'major depression', 'older persons' and 'treatments'. Two reviewers will independently select the eligible articles. For each included article, the two reviewers will independently extract the data and assess the risk of bias using the Cochrane revised tool for risk of bias. Bayesian network meta-analyses will be conducted to pool the depression scores (based on standardised mean difference) and the all-cause discontinuation across all included studies. The ranking probabilities for all interventions will be estimated and the hierarchy of each intervention will be summarised as surface under the cumulative ranking curve (SUCRA). Meta-regression and sub-group analyses will also be performed to evaluate the effect of study-level covariates. The quality of the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Ethics and dissemination

The results will be disseminated through conference presentations and peer-reviewed publications. They will provide the consolidated evidence to inform clinicians on the best choice of intervention to address major depression in older persons.

PROSPERO registration number

CRD42017075756.



http://ift.tt/2BiHdXq

Time trends in peripheral artery disease incidence, prevalence and secondary preventive therapy: a cohort study in The Health Improvement Network in the UK

Objectives

To assess time trends in symptomatic peripheral artery disease (PAD) incidence and prevalence, and secondary preventive therapy.

Design

Cohort study using The Health Improvement Network.

Setting

UK primary care.

Participants

Individuals aged 50–89 years identified annually between 2000 and 2014. Participants with symptomatic PAD were identified using Read codes.

Outcome measures

Incidence and prevalence of symptomatic PAD from 2000 to 2014, overall and by sex and age. Proportion of patients prescribed secondary preventive therapy with acetylsalicylic acid (ASA), clopidogrel, an ACE inhibitor, an angiotensin receptor blocker (ARB) and/or a statin.

Results

The incidence of symptomatic PAD per 10 000 person-years decreased over time, from 38.6 (men: 51.0; women: 28.7) in 2000 to 17.3 (men: 23.1; women: 12.4) in 2014. The prevalence of symptomatic PAD decreased from 3.4% (men: 4.5%; women: 2.5%) in 2000 to 2.4% (men: 3.1%; women: 1.7%) in 2014. Incidence and prevalence decreases were observed in all age groups. The proportions of patients prescribed ASA monotherapy, clopidogrel monotherapy and dual antiplatelet therapy in the 2 months after PAD diagnosis were 42.7%, 2.9% and 2.5%, respectively, during 2000–2003, and 44.7%, 11.0% and 5.2%, respectively, during 2012–2014. For ACE inhibitor/ARB therapy and statins, proportions in the 2 months after diagnosis were 30.2% and 31.2%, respectively, during 2000–2003, and 45.1% and 65.9%, respectively, during 2012–2014.

Conclusion

The incidence and prevalence of symptomatic PAD diagnosed in UK primary care are decreasing. A large proportion of the population with PAD in clinical practice does not receive guideline-recommended secondary prevention therapy.



http://ift.tt/2mWRt3h

Monitoring intensive care unit performance--impact of a novel individualised performance scorecard in critical care medicine: a mixed-methods study protocol

Introduction

Patients admitted to a critical care medicine (CCM) environment, including an intensive care unit (ICU), are susceptible to harm and significant resource utilisation. Therefore, a strategy to optimise provider performance is required. Performance scorecards are used by institutions for the purposes of driving quality improvement. There is no widely accepted or standardised scorecard that has been used for overall CCM performance. We aim to improve quality of care, patient safety and patient/family experience in CCM practice through the utilisation of a standardised, repeatable and multidimensional performance scorecard, designed to provide a continuous review of ICU physician and nurse practice, as well as departmental metrics.

Methods and analysis

This will be a mixed-methods, controlled before and after study to assess the impact of a CCM-specific quality scorecard. Scorecard metrics were developed through expert consensus and existing literature. The study will include 19 attending CCM physicians and approximately 300 CCM nurses. Patient data for scorecard compilation are collected daily from bedside flow sheets. Preintervention baseline data will be collected for 6 months for each participant. After this, each participant will receive their scorecard measures. Following a 3-month washout period, postintervention data will be collected for 6 months. The primary outcome will be change in performance metrics following the provision of scorecard feedback to subjects. A cost analysis will also be performed, with the purpose of comparing total ICU costs prior to implementation of the scorecard with total ICU costs following implementation of the scorecard. The qualitative portion will include interviews with participants following the intervention phase. Interviews will be analysed in order to identify recurrent themes and subthemes, for the purposes of driving scorecard improvement.

Ethics and dissemination

This protocol has been approved by the local research ethics board. Publication of results is anticipated in 2019. If this intervention is found to improve patient- and unit-directed outcomes, with evidence of cost-effectiveness, it would support the utilisation of such a scorecard as a quality standard in CCM.



http://ift.tt/2BjUSxc

The journey through care: study protocol for a longitudinal qualitative interview study to investigate the healthcare experiences and preferences of children and young people with life-limiting and life-threatening conditions and their families in the West Midlands, UK

Introduction

The number of children and young people living with life-limiting and life-threatening conditions is rising. Providing high-quality, responsive healthcare for them and for their families presents a significant challenge. Their conditions are often complex and highly unpredictable. Palliative care is advocated for people with life-limiting and life-threatening conditions, but these services for children are highly variable in terms of availability and scope. Little is known about the lived experiences and preferences of children and their families in terms of the palliative care that they do, or do not, receive. This study aims to produce an in-depth insight into the experiences and preferences of such children and families in order to develop recommendations for the future provision of services. The study will be carried out in the West Midlands, UK.

Methods and analysis

A qualitative study comprising longitudinal interviews over a 12-month period with children (aged 5–18 years) living with life-limiting or life-threatening conditions and their family members. Data analysis will start with thematic analysis, followed by narrative and cross-case analysis to examine changing experiences and preferences over time, at the family level and within the wider healthcare system. Patient and public involvement (PPI) has informed the design and conduct of the study. Findings will be used to develop recommendations for an integrated model of palliative care for children in partnership with the patient and public involvement (PPI) group.

Ethics and dissemination

Ethical approval was granted in September 2016 by the National Health Service Health Research Authority (IRAS ID: 196816, REC reference: 16/WM/0272). Findings will be of immediate relevance to healthcare providers, policy-makers, commissioners and voluntary sector organisations in the UK and internationally. Reports will be prepared for these audiences, as well as for children and their families, alongside academic outputs.



http://ift.tt/2mZAvkJ

Online versus paper-based screening for depression and anxiety in adults with cystic fibrosis in Ireland: a cross-sectional exploratory study

Objective

To compare online and paper-based screening for depression and anxiety in adults with cystic fibrosis (CF).

Design and setting

Cross-sectional study in CF clinics in Ireland and through the Cystic Fibrosis Ireland online community.

Participants

160 adult patients aged 18 or above were recruited. Of these, 147 were included in the analysis; 83 online and 64 paper-based. The remaining 13 were excluded because of incomplete data.

Measures

Depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Data on pulmonary function (forced expiratory volume in 1 s %) and body mass index were self-reported based on clinical assessments. Sociodemographic data were collected.

Results

Compared with the paper-based participants, the online participants were more likely to be female (61.7% vs 48.4%), older (mean 32.2 vs 28.2 years) and were more likely to be married (32.5% vs 15.6%), living with their spouse or partner (42.5% vs 22.6%) and working either full time (33.7% vs 15.9%) or part time (30.1%vs 17.5%). The prevalence rates of elevated anxiety and depression were not significantly different (P=0.71 and P=0.56). HADS anxiety and depression scores were not statistically different between online (P=0.83) and paper-based (P=0.92) participants based on Mann-Whitney U test. A significant negative correlation was found between depression and pulmonary function (r=–0.39, P=0.01) and anxiety and pulmonary function (r=–0.36, P=0.02). Based on Cronbach's alpha, there were no statistically significant differences between the online and paper-based participants on the internal consistency of the HADS anxiety (P=0.073) and depression (P=0.378) scales.

Conclusions

Our findings suggest that online and paper-based screening for depression and anxiety in adult patients with CF yield comparable findings on prevalence rates and scores, associations with health and internal consistency of subscales. This study highlights that online screening offers an alternative method to paper-based screening. Further research with a larger sample and assessment of measurement equivalence between online and paper based screening is needed to confirm our results.



http://ift.tt/2BkpBdx

A cross-sectional analysis of the relationship between diabetes and health access barriers in an urban First Nations population in Canada

Objective

This study explores the relationship between health access barriers and diabetes in an urban First Nations population in Canada.

Design

Data from a self-identified urban First Nations population were collected using respondent-driven sampling (RDS). As no clear approach for regression modelling of RDS data is available, two logistic regression modelling approaches, including survey-based logistic and generalised linear mixed models, were used to explore the relationship between diabetes and health barriers of interest, including access to healthcare, food, housing and socioeconomic factors.

Setting

Hamilton, Ontario, Canada.

Participants

This cross-sectional study used data collected from the Our Health Counts study, in partnership with the De dwa da dehs nye>s Aboriginal Health Centre, which recruited 554 First Nations adults living in Hamilton using RDS.

Results

After adjusting for covariates, multivariable regression techniques showed a statistically significant relationship between a self-reported diagnosis of diabetes and a lack of culturally appropriate care among urban First Nations peoples (OR: 12.70, 95% CI 2.52 to 57.91). There was also a trend towards a relationship between diabetes and not having a doctor available in the area, feeling that healthcare provided was inadequate and a lack of available healthcare services in the area.

Conclusions

Urban First Nations peoples who felt the health service they received was not culturally appropriate were more likely to have diabetes, compared with those who did not feel the service they received was culturally inappropriate. Establishing more healthcare services that integrate First Nations cultures and traditions could improve access to care and the course of treatment for urban First Nations peoples living with diabetes.



http://ift.tt/2mZ6Isu

Roles of mothers and fathers in supporting child physical activity: a cross-sectional mixed-methods study

Objectives

Examine the extent that parent gender is associated with supporting children's physical activity.

Design

Cross-sectional mixed-methods study.

Setting

47 primary schools located in Bristol (UK).

Participants

944 children aged 8–9 years and one of their parents provided quantitative data; 51 parents (20 fathers) were interviewed.

Methods

Children wore an accelerometer, and mean minutes of moderate-to-vigorous physical activity (MVPA) per day, counts per minute (CPM) and achievement of national MVPA guidelines were derived. Parents reported who leads in supporting child activity during the week and weekend. Linear and logistic regression examined the association between gender of parent who supports child activity and child physical activity. For the semistructured telephone interviews, inductive and deductive content analyses were used to explore the role of gender in how parents support child activity.

Results

Parents appeared to have a stronger role in supporting boys to be more active, than girls, and the strongest associations were when they reported that both parents had equal roles in supporting their child. For example, compared with the reference of female/mother support, equal contribution from both parents during the week was associated with boys doing 5.9 (95% CI 1.2 to 10.6) more minutes of MVPA per day and more CPM when both parents support on weekday and weekends (55.1 (14.3 to 95.9) and 52.8 (1.8 to 103.7), respectively). Associations in girls were weaker and sometimes in the opposite direction, but there was no strong statistical evidence for gender interactions. Themes emerged from the qualitative data, specifically; parents proactively supporting physical activity equally, mothers supporting during the week, families getting together at weekends, families doing activities separately due to preferences and parents using activities to bond one-to-one with children.

Conclusions

Mothers primarily support child activity during the week. Children, possibly more so boys, are more active if both parents share the supporting role.



http://ift.tt/2Bjlr5N

Seremban Cohort Study (SECOST): a prospective study of determinants and pregnancy outcomes of maternal glycaemia in Malaysia

Introduction

Both gestational diabetes mellitus (GDM) and hyperglycaemia less severe than GDM are associated with risk of adverse pregnancy outcomes. We describe the study design of a prospective cohort of pregnant women recruited in early pregnancy with follow-ups of mothers and infants up to 2 years after birth. The primary aim of the study was to identify the determinants and outcomes of maternal glycaemia.

Methods and analysis

Seremban Cohort Study (SECOST) is an ongoing prospective cohort study in which eligible pregnant women in first trimester (<10 weeks of gestation) are recruited from Maternal and Child Health clinics in Seremban District, Negeri Sembilan with seven follow-ups during pregnancy through 2 years postnatally. Infants are followed up every 6 months after birth until 2 years old. A standard 75 g oral glucose tolerance test is performed between 24 and 32 of weeks of gestation and as close to 28 weeks of gestation. Pregnancy and birth information are obtained from medical records. Sociodemographic, anthropometric, biochemical, dietary, physical activity, smoking, depression, child feeding and other data of mothers and infants are obtained at follow-ups.

Ethics and dissemination

This study is approved by the Medical Research Ethics Committee (MREC), Universiti Putra Malaysia (UPM/FPSK/100-9/2-MJKEtika) and MREC, Ministry of Health Malaysia (KKM/NIHSEC/08/0804/P12- 613). Permission to conduct this study is also obtained from the Head of Seremban District Health Office. All participants are required to provide written informed consent prior to data collection. The research findings will be disseminated at journals and conference presentations.



http://ift.tt/2mZ8kCC

Correction: Design and rationale of the Cardiovascular Health and Text Messaging (CHAT) Study and the CHAT-Diabetes Mellitus (CHAT-DM) Study: two randomised controlled trials of text messaging to improve secondary prevention for coronary heart disease and diabetes

Huo X, Spatz ES, Ding Q, et al. Design and rationale of the Cardiovascular Health and Text Messaging (CHAT) Study and the CHAT-Diabetes Mellitus (CHAT-DM) Study: two randomised controlled trials of text messaging to improve secondary prevention for coronary heart disease and diabetes. BMJ Open 2017;7:e018302. doi: 10.1136/bmjopen-2017-018302

The equal contributors statement should read: "XH and ESS are Joint first authors. HMK and LJ are Joint senior authors."

The 'Contributions' section at the end of the paper should read: "ESS, XZ, MLI, JL, XL, LJ, JAS, FAM, HMK, LJ: study concept and design; All authors except XY, HZ are involved in designing the study text messages; XH, XZ, HZ, XY, XL are involved in the implementation of the project; XH, ESS, QD, PH, CM drafting the initial manuscript. All authors provided critical revision of the paper, read and approved the final manuscript."



http://ift.tt/2BiHbPi

Longitudinal impact of interprofessional education on attitudes, skills and career trajectories: a protocol for a quasi{-}experimental study in New Zealand

Introduction

Interprofessional practice is recognised as an important element of safe and effective healthcare. However, few studies exist that evaluate how preregistration education contributes to interprofessional competencies, and how these competencies develop throughout the early years of a health professional's career. This quasiexperimental study will gather longitudinal data during students' last year of preregistration training and their first 3 years of professional practice to evaluate the ongoing development of interprofessional competencies and the influence that preregistration education including an explicit interprofessional education (IPE) programme may have on these.

Methods and analysis

Participants are students and graduates from the disciplines of dentistry, dietetics, medicine, nursing, occupational therapy, oral health, pharmacy and physiotherapy recruited before their final year of study. A subset of these students attended a 5-week IPE immersion programme during their final year of training. All data will be collected via five written or electronic surveys completed at 12-month intervals. Each survey will contain the Attitudes Towards Health Care Teams Scale and the Team Skills Scale, as well as quantitative and free-text items to explore vocational satisfaction, career trajectories and influences on these. Students who attend the IPE programme will complete additional free-text items to explore the effects of this programme on their careers. Quantitative analysis will compare scores at each time point, adjusted for baseline scores, for graduates who did and did not participate in the IPE programme. Associations between satisfaction data and discipline, professional setting, location and IPE participation will also be examined. Template analysis will explore free-text themes related to influences on career choices including participation in preregistration IPE.

Ethics and dissemination

This study has received approval from the University of Otago Ethics Committee (D13/019). Results will be disseminated through peer-reviewed publications, conferences and stakeholder reports. Findings will inform future IPE developments and health workforce planning.



http://ift.tt/2n2DZD5

Impacts of Bicycle Infrastructure in Mid-Sized Cities (IBIMS): protocol for a natural experiment study in three Canadian cities

Introduction

Bicycling is promoted as a transportation and population health strategy globally. Yet bicycling has low uptake in North America (1%–2% of trips) compared with European bicycling cities (15%–40% of trips) and shows marked sex and age trends. Safety concerns due to collisions with motor vehicles are primary barriers.

To attract the broader population to bicycling, many cities are making investments in bicycle infrastructure. These interventions hold promise for improving population health given the potential for increased physical activity and improved safety, but such outcomes have been largely unstudied. In 2016, the City of Victoria, Canada, committed to build a connected network of infrastructure that separates bicycles from motor vehicles, designed to attract people of 'all ages and abilities' to bicycling.

This natural experiment study examines the impacts of the City of Victoria's investment in a bicycle network on active travel and safety outcomes. The specific objectives are to (1) estimate changes in active travel, perceived safety and bicycle safety incidents; (2) analyse spatial inequities in access to bicycle infrastructure and safety incidents; and (3) assess health-related economic benefits.

Methods and analysis

The study is in three Canadian cities (intervention: Victoria; comparison: Kelowna, Halifax). We will administer population-based surveys in 2016, 2018 and 2021 (1000 people/city). The primary outcome is the proportion of people reporting bicycling. Secondary outcomes are perceived safety and bicycle safety incidents. Spatial analyses will compare the distribution of bicycle infrastructure and bicycle safety incidents across neighbourhoods and across time. We will also calculate the economic benefits of bicycling using WHO's Health Economic Assessment Tool.

Ethics and dissemination

This study received approval from the Simon Fraser University Office of Research Ethics (study no. 2016s0401). Findings will be disseminated via a website, presentations to stakeholders, at academic conferences and through peer-reviewed journal articles.



http://ift.tt/2BiLutQ

Randomised controlled trial to determine the efficacy and safety of prescribed water intake to prevent kidney failure due to autosomal dominant polycystic kidney disease (PREVENT-ADPKD)

Introduction

Maintaining fluid intake sufficient to reduce arginine vasopressin (AVP) secretion has been hypothesised to slow kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). However, evidence to support this as a clinical practice recommendation is of poor quality. The aim of the present study is to determine the long-term efficacy and safety of prescribed water intake to prevent the progression of height-adjusted total kidney volume (ht-TKV) in patients with chronic kidney disease (stages 1–3) due to ADPKD.

Methods and analysis

A multicentre, prospective, parallel-group, open-label, randomised controlled trial will be conducted. Patients with ADPKD (n=180; age ≤65 years, estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2) will be randomised (1:1) to either the control (standard treatment+usual fluid intake) or intervention (standard treatment+prescribed fluid intake) group. Participants in the intervention arm will be prescribed an individualised daily fluid intake to reduce urine osmolality to ≤270 mOsmol/kg, and supported with structured clinic and telephonic dietetic review, self-monitoring of urine-specific gravity, short message service text reminders and internet-based tools. All participants will have 6-monthly follow-up visits, and ht-TKV will be measured by MRI at 0, 18 and 36 months. The primary end point is the annual rate of change in ht-TKV as determined by serial renal MRI in control vs intervention groups, from baseline to 3 years. The secondary end points are differences between the two groups in systemic AVP activity, renal disease (eGFR, blood pressure, renal pain), patient adherence, acceptability and safety.

Ethics and dissemination

The trial was approved by the Human Research Ethics Committee, Western Sydney Local Health District. The results will inform clinicians, patients and policy-makers regarding the long-term safety, efficacy and feasibility of prescribed fluid intake as an approach to reduce kidney cyst growth in patients with ADPKD.

Trial registration number

ANZCTR12614001216606.



http://ift.tt/2mYJkuW

Understanding the use of email consultation in primary care using a retrospective observational study with data of Dutch electronic health records

Objectives

It is unclear why the use of email consultation is not more widespread in Dutch general practice, particularly because, since 2006, its costs can be reimbursed. To encourage further implementation, it is needed to understand the current use of email consultations. This study aims to understand the use of email consultation by different patient groups, compared with other general practice (GP) consultations.

Setting

For this retrospective observational study, we used Dutch routine electronic health record data obtained from NIVEL Primary Care Database for the years 2010 and 2014.

Participants

200 general practices were included in 2010 (734 122 registered patients) and 434 in 2014 (1 630 386 registered patients).

Primary outcome measures

The number and percentage of email consultations and patient characteristics (age, gender, neighbourhood socioeconomic status and diagnoses) of email consultation users were investigated and compared with those who had a telephone or face-to-face consultation. General practice characteristics were also taken into account.

Results

32.0% of the Dutch general practices had at least one email consultation in 2010, rising to 52.8% in 2014. In 2014, only 0.7% of the GP consultations were by email (the others comprised home visits, telephone and face-to-face consultations). Its use highly varied among general practices. Most email consultations were done for psychological (14.7%); endocrine, metabolic and nutritional (10.9%); and circulatory (10.7%) problems. These diagnosis categories appeared less frequently in telephone and face-to-face consultations. Patients who had an email consultation were older than patients who had a telephone or face-to-face consultation. In contrast, patients with diabetes who had an email consultation were younger.

Conclusion

Even though email consultation was done in half the general practices in the Netherlands in 2014, the actual use of it is extremely low. Patients who had an email consultation differ from those who had a telephone or face-to-face consultation. In addition, the use of email consultation by patients is dependent on its provision by GPs.



http://ift.tt/2BiBa51

Incidence and mortality of fractures by frailty level over 80 years of age: cohort study using UK electronic health records

Objective

This study aimed to estimate the association of frailty with incidence and mortality of fractures at different sites in people aged over 80 years.

Design

Cohort study.

Setting

UK family practices from 2001 to 2014.

Participants

265 195 registered participants aged 80 years and older.

Measurements

Frailty status classified into 'fit', 'mild', 'moderate' and 'severe' frailty. Fractures, classified into non-fragility and fragility, including fractures of femur, pelvis, shoulder and upper arm, and forearm/wrist. Incidence of fracture, and mortality within 90 days and 1 year, were estimated.

Results

There were 28 643 fractures including: non-fragility fractures, 9101; femur, 12 501; pelvis, 2172; shoulder and upper arm, 4965; and forearm/wrist, 6315. The incidence of each fracture type was higher in women and increased with frailty category (femur, severe frailty compared with 'fit', incidence rate ratio (IRR) 2.4, 95% CI 2.3 to 2.6). Fractures of the femur (95–99 years compared with 80–84 years, IRR 2.7, 95% CI 2.6 to 2.9) and pelvis (IRR 2.9, 95% CI 2.5 to 3.3) were strongly associated with age but non-fragility and forearm fractures were not. Mortality within 90 days was greatest for femur fracture (adjusted HR, compared with forearm fracture 4.3, 95% CI 3.7 to 5.1). Mortality was higher in men and increased with age (HR 5.3, 95% CI 4.3 to 6.5 in those over 100 years compared with 80–84 years) but was less strongly associated with frailty category. Similar associations with fractures were seen at 1-year mortality.

Conclusions

The incidence of fractures at all sites was higher in women and strongly associated with advancing frailty status, while the risk of mortality after a fracture was greater in men and was associated with age rather than frailty category.



http://ift.tt/2n0Fxxe

Home-based exercise therapy in patients awaiting liver transplantation: protocol for an observational feasibility trial

Introduction

Liver disease is the third most common cause of premature mortality in the UK. Liver failure accelerates frailty, resulting in skeletal muscle atrophy, functional decline and an associated risk of liver transplant waiting list mortality. However, there is limited research investigating the impact of exercise on patient outcomes pre and post liver transplantation. The waitlist period for patients listed for liver transplantation provides a unique opportunity to provide and assess interventions such as prehabilitation.

Methods and analysis

This study is a phase I observational study evaluating the feasibility of conducting a randomised control trial (RCT) investigating the use of a home-based exercise programme (HBEP) in the management of patients awaiting liver transplantation. Twenty eligible patients will be randomly selected from the Queen Elizabeth University Hospital Birmingham liver transplant waiting list. Participants will be provided with an individually tailored 12-week HBEP, including step targets and resistance exercises. Activity trackers and patient diaries will be provided to support data collection. For the initial 6 weeks, telephone support will be given to discuss compliance with the study intervention, achievement of weekly targets, and to address any queries or concerns regarding the intervention. During weeks 6–12, participants will continue the intervention without telephone support to evaluate longer term adherence to the study intervention. On completing the intervention, all participants will be invited to engage in a focus group to discuss their experiences and the feasibility of an RCT.

Ethics and dissemination

The protocol is approved by the National Research Ethics Service Committee North West - Greater Manchester East and Health Research Authority (REC reference: 17/NW/0120). Recruitment into the study started in April 2017 and ended in July 2017. Follow-up of participants is ongoing and due to finish by the end of 2017. The findings of this study will be disseminated through peer-reviewed publications and international presentations. In addition, the protocol will be placed on the British Liver Trust website for public access.

Trial registration number

NCT02949505; Pre-results.



http://ift.tt/2BiB1P1

Depressive symptoms predict head and neck cancer survival: Examining plausible behavioral and biological pathways

BACKGROUND

Head and neck cancers are associated with high rates of depression, which may increase the risk for poorer immediate and long-term outcomes. Here it was hypothesized that greater depressive symptoms would predict earlier mortality, and behavioral (treatment interruption) and biological (treatment response) mediators were examined.

METHODS

Patients (n = 134) reported depressive symptomatology at treatment planning. Clinical data were reviewed at the 2-year follow-up.

RESULTS

Greater depressive symptoms were associated with significantly shorter survival (hazard ratio, 0.868; 95% confidence interval [CI], 0.819-0.921; P < .001), higher rates of chemoradiation interruption (odds ratio, 0.865; 95% CI, 0.774-0.966; P = .010), and poorer treatment response (odds ratio, 0.879; 95% CI, 0.803-0.963; P = .005). The poorer treatment response partially explained the depression-survival relation. Other known prognostic indicators did not challenge these results.

CONCLUSIONS

Depressive symptoms at the time of treatment planning predict overall 2-year mortality. Effects are partly influenced by the treatment response. Depression screening and intervention may be beneficial. Future studies should examine parallel biological pathways linking depression to cancer survival, including endocrine disruption and inflammation. Cancer 2018. © 2018 American Cancer Society.



http://ift.tt/2DpNWAG

Point-of-care hemoglobin testing for postmortem diagnosis of anemia

Abstract

An autopsy involves examination of a body using invasive methods such as dissection, and includes various tests using samples procured during dissection. During medicolegal autopsies, the blood carboxyhemoglobin concentration is commonly measured using the AVOXimeter® 4000 as a point-of-care test. When evaluating the body following hypovolemic shock, characteristics such as reduced livor mortis or an anemic appearance of the viscera can be identified, but these observations arequite subjective. Thus, a more objective test is required for the postmortem diagnosis of anemia. In the present study, the AVOXimeter® 4000 was used to investigate the utility of point-of-care hemoglobin testing. Hemoglobin tests were performed in 93 autopsy cases. The AVOXimeter® 4000 and the BC-2800 Auto Hematology Analyzer were used to test identical samples in 29 of these cases. The results of hemoglobin tests performed with these two devices were statistically similar (r = 0.969). The results of hemoglobin tests using postmortem blood were compared with antemortem test results from medical records from 31 cases, and these results were similar. In 13 of 17 cases of death from internal hemorrhage, hemoglobin levels were lower in the cardiac blood than in blood from the affected body cavity, likely due to compensatory changes induced by antemortem hemorrhage. It is concluded that blood hemoglobin testing may be useful as a point-of-care test for diagnosing postmortem anemia.



http://ift.tt/2G53Ylm

Issue Information

No abstract is available for this article.



http://ift.tt/2DXC9dV

Issue highlights



http://ift.tt/2Dl63HR

Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

Abstract
Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = −0.24 to −0.73; P < 1.49 × 10−4), and lower thickness in the precentral gyri bilaterally (d = −0.34 to −0.52; P < 4.31 × 10−6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = −1.73 to −1.91, P < 1.4 × 10−19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = −0.36 to −0.52; P < 1.49 × 10−4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = −0.29 to −0.54; P < 1.49 × 10−4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = −0.27 to −0.51; P < 1.49 × 10−4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < −0.0018; P < 1.49 × 10−4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed.

http://ift.tt/2mWQ7or

Percutaneous Contrast Echocardiography-guided Intramyocardial Injection and Cell Delivery in a Large Preclinical Model

Novel therapeutic strategies in cardiac regenerative medicine require extensive and detailed studies in large preclinical animal models before they can be considered for use in humans. Here, we demonstrate a percutaneous contrast echocardiography-guided intramyocardial injection technique in rabbits, which is valuable for hypothesis testing the efficacy of such novel therapies.

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Peroneus brevis tendon in proximal 5th metatarsal fractures: anatomical considerations for safe hook plate placement

Publication date: Available online 8 January 2018
Source:Injury
Author(s): N. Seyidova, L. Hirtler, R. Windhager, R. Schuh, M. Willegger
IntroductionThe peroneus brevis tendon (PBT) inserts into the proximal aspect of the 5th metatarsal. Metatarsal bone fractures are encountered to be the most common fractures in the foot with predominantly fractures at the base of the fifth metatarsal bone. Mechanism of injury and treatment of the proximal 5th metatarsal fractures vary due to the complex anatomy and diverse biomechanical properties. The purpose of this study was to analyze the footprint of the PBT with regards to the proximal 5th metatarsal fractures and to define a "safe zone" for hook plate placement.Materials and methodsForty-one (41) fixed human lower leg specimens were dissected to expose the PBT insertion. The following footprint characteristics were evaluated: area of insertion (AOI) (mm2), length (mm), width (mm), shape and insertional variations. The position of the main PBT footprint was localized according to the Lawrence and Botte classification for the proximal 5th metatarsal fractures (Zone I–III). A "safe zone" was defined for the fracture-specific hook plate placement.ResultsIn 25 (61%) feet the PBT footprint was situated in Zone I and in 16 feet (39%) in Zone I&II. The mean AOI, length and width measured 54.5 mm2 (SD 16.5), 16.0 mm (SD 5.1) and 4.7 mm (SD 1.4), respectively. Analysis of the footprint shapes revealed four different shape types: kidney (29.3%), diamond (22.0%), crescent (31.7%) and oval (17.0%). A "safe zone" for hook plate placement without or minimal interference of the PBT at its insertion could be defined at the lateral aspect of the 5th metatarsal.ConclusionThe majority of the PBT footprints were found in Zone I. Hook plate placement demonstrated to be safe when placed strictly laterally at the proximal aspect of the 5th metatarsal. Precise knowledge of the peroneus brevis anatomy may help to better understand the biomechanical aspects of the proximal 5th metatarsal fractures.



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Functional Outcome and Health Related Quality of Life after Dual Mobility Cup Total Hip Replacement for Displaced Femoral Neck Fractures in Middle Aged Egyptian Patients

Publication date: Available online 8 January 2018
Source:Injury
Author(s): Ramy Ahmed Rashed, Hannah Sevenoaks, Amira Mohammed Shabaan, Qaisar Akhlaq Choudry, Abdullah Saeed Hammad, Mohammed Samir Kasem, Tarek Aly El Khadrawe, Magdy Mohammed El Dakhakhny
AimThis study was done to assess the functional and clinical results after one year of cemented THR with dual mobility cup for the treatment of fracture neck femur in active middle-aged patients in Egypt (Middle Eastern population).Patients and MethodsThis study included 31 patients (32 hips) with displaced femoral neck fractures that were admitted to El Hadara University Hospital, Alexandria, Egypt. Their mean age was 66.4 ± 5.9 years. Fifteen patients were females. All the patients were treated with total hip replacement using a cemented dual mobility cup (Ecofit® 2 M, Implantcast GmbH, Germany) total hip replacement through the standard posterior approach. Functional assessment was done using Harris Hip Score (HHS), SF-36 questionnaire for health related quality of life (HRQoL) with assistance of a physiotherapist.ResultsThe mean HHS improved over the follow up period from 79.04 ± 7.9 at 12 weeks to an average of 92.8 ± 11.1 at 1 year follow up. HRQoL measures showed a pattern of initial drop at 3 months postoperatively, then a steady rise to be restored at 1 year as compared to the preoperative baseline measures. There were no dislocations encountered in this series over one year follow up. The following complications were encountered; 1 deep infection, 2 deep vein thrombosis, 2 heterotopic ossifications, and 1 patient died within one year after surgery.ConclusionsDual mobility cup total hip replacement is an acceptable method for treatment of displaced femoral neck fracture in active middle aged patients in Egypt as it provides pain relief and good function without compromising the stability.



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Simulation-based multidisciplinary team training decreases time to critical operations for trauma patients

Publication date: Available online 8 January 2018
Source:Injury
Author(s): Margaret Murphy, Kate Curtis, Mary K. Lam, Cameron S. Palmer, Jeremy Hsu, Andrea McCloughen
BackgroundSimulation has been promoted as a platform for training trauma teams. However, it is not clear if this training has an impact on health service delivery and patient outcomes. This study evaluates the association between implementation of a simulation based multidisciplinary trauma team training program at a metropolitan trauma centre and subsequent patient outcomes.MethodThis was a retrospective review of trauma registry data collected at an 850-bed Level 1 Adult Trauma Centre in Sydney, Australia. Two concurrent four-year periods, before and after implementation of a simulation based multidisciplinary trauma team training program were compared for differences in time to critical operations, Emergency Department (ED) length of stay (LOS) and patient mortality.ResultsThere were 2389 major trauma patients admitted to the hospital during the study, 1116 in the four years preceding trauma team training (the PREgroup) and 1273 in the subsequent 4 years (the POST group). There were no differences between the groups with respect to gender, body region injured, incidence of polytrauma, and pattern of arrival to ED. The POST group was older (median age 54 versus 43 years, p < 0.001) and had a higher incidence of falls and assaults (p < 0.001). There was a reduction in time to critical operation, from 2.63 hours (IQR 1.23-5.12) in the PRE-group to 0.55 hours (IQR 0.22–1.27) in the POST-group, p < 0.001. The overall ED LOS increased, and there was no reduction in mortality. Post-hoc analysis found LOS in ED was reduced in the cohort requiring critical operations, p < 0.001.ConclusionThe implementation of trauma team training was associated with a reduction in time to critical operation while overall ED length of stay increased. Simulation is promoted as a platform for training teams; but the complexity of trauma care challenges efforts to demonstrate direct links between multidisciplinary team training and improved outcomes. There remain considerable gaps in knowledge as to how team training impacts health service delivery and patient outcomes.Level of evidenceRetrospective comparative therapeutic/care management study, Level III evidence.



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ICS classification system of infected osteosynthesis: long-term results

Publication date: Available online 6 January 2018
Source:Injury
Author(s): Carlo L. Romano, Ilaria Morelli, Delia Romano, Enzo Meani, Lorenzo Drago
The best treatment strategy for infected osteosyntheses is still debated. While hardware removal or eventually early device exchange may be necessary in most of the cases, temporary hardware retention until fracture healing can be a valid alternative option in others. Aim of the present study is to report the long-term results of 215 patients with infected osteosyntheses, treated according to the ICS (Infection, Callus, Stability) classification in two Italian hospitals. Patients classified as ICS Type 1 (N = 83) feature callus progression and hardware stability, in spite of the presence of infection; these patients were treated with suppressive antibiotic therapy coupled with local debridement in 18.1% of the cases, and no hardware removal until bone healing. Type 2 patients (N = 75) are characterized by the presence of infection and hardware stability, but no callus progression; these patients were treated as Type 1 patients, but with additional callus stimulation therapies. Type 3 patients (N = 57), showing infection, no callus progression and loss of hardware stability, underwent removal and exchange of the fixation device. Considering only the initial treatment, performed according to the ICS classification, at a minimum 5 years follow up, 89.3% achieved bone healing and 93.5% did not show infection recurrence. The ICS classification appears as a useful and reliable tool to help standardizing the decision-making process in treating infected osteosynthesis with the most conservative approach.



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Baseline and pre-operative 1-year mortality risk factors in a cohort of 509 hip fracture patients consecutively admitted to a co-managed orthogeriatric unit (FONDA Cohort)

Publication date: Available online 6 January 2018
Source:Injury
Author(s): Rocío Menéndez-Colino, Teresa Alarcon, Pilar Gotor, Rocío Queipo, Raquel Ramírez-Martín, Angel Otero, Juan I. González-Montalvo
IntroductionThe aim of this study was to determine the patient characteristics that predict 1-year mortality after a hip fracture (HF).MethodsAll patients admitted consecutively with fragility HF during 1 year in a co-managed orthogeriatric unit of a university hospital (FONDA cohort) were assesed. Baseline and admission demographic, clinical, functional, analytical and body-composition variables were collected in the first 72 hours after admission. A protocol designed to minimize the consequences of the HF was applied. One year after the fracture patients or their carers were contacted by telephone to ascertain their vital status.ResultsA total of 509 patients with a mean age of 85.6 years were included. One-year mortality was 23.2%. The final multivariate model included 8 independent mortality risk factors: age >85 years, baseline functional impairment in basic activities of daily living, low body mass index, cognitive impairment, heart disease, low hand-grip strength, anaemia at admission, and secondary hyperparathyroidism associated with vitamin D deficiency. The association of several of these factors greatly increased mortality risk, with an OR (95% confidence interval [CI]) of 5.372 (3.227–8.806) in patients with 4 to 5 factors, and an OR (95% CI) of 11.097 (6.432–19.144) in those with 6 or more factors.ConclusionsIn addition to previously known factors (such as age, impairment in basic activities of daily living, cognitive impairment, malnutrition and anaemia at admission), other factors, such as muscle strength and hyperparathyroidism associated with vitamin D deficiency, are associated with greater 1-year mortality after a HF.



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A new sign allowing diagnosis in the pathologies of the extensor tendons of the hand.

Publication date: Available online 9 January 2018
Source:Injury
Author(s): A. Leti Acciaro, F. Pilla, G. Colzani, N. Corradi
IntroductionThe thorough knowledge of the anatomy of the extensor tendon system of the hand is crucial for clinical examination and detection of tendon injuries. The Juncturae between the EDCII and other extensor tendons presents different incidences, shapes ("r" or "y") and morphologies (Type I, II, III). The EIP does not receive connection. These characteristics may result in variable effects on extensor tendons during active finger movements. The purpose of this study is to investigate and describe a new sign helping diagnosis for injuries or pathologies of EIP and EDC index finger (EDC II), based on a cadaveric dissection and clinical observation.Materials and methodsThe authors performed a clinical observational study in 520 patients in order to distinctly evaluate by means of inspection and palpation the EIP and EDC II tendons and an anatomical analysis of extensor tendon apparatus of long fingers was then performed in 89 cadaver hands focusing the investigation on the juncturae system.ResultsThe observational studies showed that during the flexion of the III, IV and V fingers, associated to the active extension of the I and II fingers, the EDC of the III, IV and V fingers moved the EDC II in ulnar direction by means of juncturae action. The EIP remained in its position becoming visible and isolated from the migrated EDC II.ConclusionsThis feature allows the distinct clinical evaluation by observation and palpation of both EDC II and EIP tendons and may be helpful in clinical conditions such as diagnosis of tendon lesions, pre-operative planning of EIP transfer and extensor tendon tenolysis associated to soft tissue scar at the second MPj.



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Absorption of Nasal and Bronchial Fluids: Precision Sampling of the Human Respiratory Mucosa and Laboratory Processing of Samples

This manuscript describes the use of nasal and bronchial absorption techniques, specifically using synthetic absorptive matrices (SAM) to sample the mucosal lining fluid (MLF) of the upper and lower airway. These methods provide better standardization and tolerability than existing respiratory sampling techniques.

http://ift.tt/2DuonSr

In Vivo Multimodal Imaging and Analysis of Mouse Laser-Induced Choroidal Neovascularization Model

56173fig1.jpg

Here, we present the usefulness of longitudinal in vivo imaging in the follow-up of morphological changes of laser-induced choroidal neovascularization in mice.

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Lysosomal Acid Lipase Deficiency: Report of Five Cases across the Age Spectrum

Lysosomal acid lipase (LAL) deficiency is an autosomal recessive lysosomal storage disorder caused by mutations in the LIPA gene that leads to premature organ damage and mortality. We present retrospective data from medical records of 5 Brazilian patients, showing the broad clinical spectrum of the disease.

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Maternal, Fetal, and Neonatal Outcomes in Pregnant Dengue Patients in Mexico

To increase our understanding of the consequences of dengue virus infection during pregnancy, a retrospective analysis was performed on the medical records of all completed pregnancies (live births and pregnancy losses) at nine public hospitals in the Gulf of Mexico from January to October 2013. Eighty-two patients developed clinical, laboratory-confirmed dengue virus infections while pregnant. Of these, 54 (65.9%) patients were diagnosed with dengue without warning signs, 15 (18.3%) patients were diagnosed with dengue with warning signs, and 13 (15.9%) patients had severe dengue. Five (38.5%) patients with severe dengue experienced fetal distress and underwent emergency cesarean sections. Four patients delivered apparently healthy infants of normal birthweight while the remaining patient delivered a premature infant of low birthweight. Patients died of multiple organ failure during or within 10 days of the procedure. Severe dengue was also associated with obstetric hemorrhage (30.8%, four cases), preeclampsia (15.4%, two cases), and eclampsia (7.7%, one case). These complications were less common or absent in patients in the other two disease categories. Additionally, nonsevere dengue was not associated with maternal mortality, fetal distress, or adverse neonatal outcomes. In summary, the study provides evidence that severe dengue during pregnancy is associated with a high rate of fetal distress, cesarean delivery, and maternal mortality.

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Mechanism of Azalomycin F5a against Methicillin-Resistant Staphylococcus aureus

To investigate the mechanism of azalomycin against methicillin-resistant Staphylococcus aureus (MRSA), the conductivity of MRSA suspension and the adenylate kinase activity of MRSA culture were determined with the intervention of azalomycin , which were significantly increased compared to those of blank controls. This inferred that azalomycin could lead to the leakage of cellular substances possibly by increasing permeability to kill MRSA. As phospholipid bilayer was mainly responsible for cell-membrane permeability, the interaction between azalomycin and cell-membrane lipids was further researched by determining the anti-MRSA activities of azalomycin combined with cell-membrane lipids extracted from test MRSA or with 1,2-dipalmitoyl-sn-glycero-3-phospho-glycerol (DPPG) for possible molecular targets lying in MRSA cell-membrane. The results indicated that the anti-MRSA activity of azalomycin remarkably decreased when it combined with membrane lipids or DPPG. This indicated that cell-membrane lipids especially DPPG might be important targets of azalomycin against MRSA.

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Prognostic Roles of mRNA Expression of S100 in Non-Small-Cell Lung Cancer

The S100 protein family is involved in cancer cell invasion and metastasis, but its prognostic value in non-small-cell lung cancer (NSCLC) has not been elucidated. In the present study we investigated the prognostic role of mRNA expression of each individual S100 in NSCLC patients through the Kaplan–Meier plotter (KM plotter) database. Expression of 14 members of the S100 family correlated with overall survival (OS) for all NSCLC patients; 18 members were associated with OS in adenocarcinoma, but none were associated with OS in squamous cell carcinoma. In particular, high mRNA expression level of S100B was associated with better OS in NSCLC patients. The prognostic value of S100 according to smoking status, pathological grades, clinical stages, and chemotherapeutic treatment of NSCLC was further assessed. Although the results should be further verified in clinical trials our findings provide new insights into the prognostic roles of S100 proteins in NSCLC and might promote development of S100-targeted inhibitors for the treatment of NSCLC.

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Expression analysis of High-mobility group box-1 (HMGB1) in histologic samples of malignant pleural mesothelioma

Abstract

Aims

High-mobility group box-1 (HMGB1) is a chromatin structural protein, ubiquitously expressed in the nuclei of mammalian cells. When transported extracellularly, it acts as tumor suppressor and oncogenic protein. In malignant pleural mesothelioma (MPM), high serum levels of High-mobility group box-1 (HMGB1) have been related to a poor prognosis. Conversely the significance of HMGB1 expression in malignant pleural mesothelioma (MPM) tissues is still unclear.

Methods and results

Biopsy samples from 170 patients with MPM were assessed by immunohistochemistry and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) to evaluate HMGB1 protein and gene expression. The expression level of HMGB1 protein was scored using a semi-quantitative system, that sums the intensity (0-3) and the percentage (from 0-4) of positively stained cells, in nuclei, cytoplasm and in both. The final score was considered as high (>3) or low (<3) expression. Gene expression levels were calculated with ΔΔCt method. High expression levels of HMGB1 as total (P = 0,0011) and cytoplasmic score (P = 0,0462), were related with a worse disease-specific survival (DSS) in the entire cohort and in the clinicopathologic subgroups. No significant correlation was found between HMGB1 gene expression and DSS.

Conclusions

These findings indicate that HMGB1 may be a useful prognostic biomarker in MPM when detected by immunohistochemistry. Conversely, since it is expressed also in normal and reactive mesothelial cells, HMGB1 can not be considered a diagnostic biomarker, in histologic samples of mesothelioma.

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Analysis of the skin mycobiome in adult patients with atopic dermatitis

Abstract

With the recent availability of culture-independent sequencing methods, studies have been conducted to analyze skin microorganisms present in patients with atopic dermatitis (AD). However, the database on the skin fungal communities, "mycobiome," has been relatively restrictive compared with the bacterial world. We aimed to comparatively analyze the overall skin mycobiome between patients with AD and healthy individuals in the Korean population. We analyzed skin swab samples obtained from the antecubital fossae of 8 patients with AD and 8 healthy controls. Using sequencing method followed by direct DNA extraction and molecular PCR, taxonomic compositions of fungi at stepwise level ranks were analyzed. The phylogenic marker used was internal transcribed spacer 2 regions of DNA. We observed the tendency of higher intra- and inter-personal taxonomic diversity at genus and species levels in AD samples. Non-Malassezia fungal diversity was also noticeable in the patient group compared with healthy controls. Malassezia globosa and Malassezia restricta were prevalent in all samples across both study groups, and some Malassezia species, including Malassezia sloofiae and dermatis characterized AD. Our data might provide a new insight into the mycobiome of adult AD, which contributes to building a systemic mycobiome database in AD.

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Seasonal changes in epidermal ceramides are linked to impaired barrier function in acne patients

Abstract

Acne skin demonstrates increased transepidermal water loss (TEWL) compared with healthy skin, which may be due, in part, to altered ceramide levels. We analysed ceramides in the stratum corneum of healthy and acne skin, and studied seasonal variation over the course of a year. Using ultraperformance liquid chromatography with electrospray ionisation and tandem mass spectrometry (UPLC/ESI-MS/MS), we identified 283 ceramides. Acne-affected skin demonstrated overall lower levels of ceramides, with notable reductions in CER[NH] and CER[AH] ceramides, as well as the acylceramides CER[EOS] and CER[EOH]; these differences were more apparent in the winter months. Lower ceramide levels reflected an increase in TEWL in acne, compared with healthy skin, which partly resolves in the summer. Individual ceramide species with 18-carbon 6-hydroxysphingosine (H) bases (including CER[N(24)H(18)], CER[N(26)H(18)], CER[A(24)H(18)], CER[A(26)H(18)]) were significantly reduced in acne skin, suggesting that CER[NH] and CER[AH] species may be particularly important in a healthy skin barrier.

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Pantoea agglomerans Infections in Children: Report of Two Cases

Introduction. Pantoea agglomerans, primarily an environmental and agricultural organism has been reported as both commensal and pathogen of humans. We present two case reports of P. agglomerans infections in children that involved the meninges and bloodstream. Case Presentations. A 6-month-old female baby, diagnosed as congenital hydrocephalus secondary to aqueduct stenosis with ventriculoperitoneal shunt in situ, operated 14 days back was brought to the pediatric emergency with a two-day history of high fever associated with vomiting, irritability, excessive crying, and decreased feeding. Postoperative meningitis was confirmed as cerebrospinal fluid culture revealed P. agglomerans. She responded well with a 14-day intravenous (IV) course of ceftriaxone. Also, we report a case of a 3-year-old male child referred to our center with a provisional diagnosis of UTI with chickenpox for further evaluation. During his 24-hour stay at the local hospital, he had received oral antibiotics and urinary catherization. Urine culture of catheter clamp urine was sterile. P. agglomerans was grown in blood culture. He was treated successfully with IV ceftriaxone and amikacin. Conclusion. P. agglomerans can cause postsurgical meningitis and bloodstream infection in children. The clinical course of infection was mild and timely administration of proper antibiotic resulted in a favorable outcome.

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