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Σάββατο 7 Απριλίου 2018

Early Detection of Undiagnosed Hypertension Based on Occupational Screening in the Hotel and Restaurant Industry

Blood pressure is the most important, modifiable risk factor for cardiovascular diseases. Lifestyle factors and also workload are the main, potential risk factors for the development of hypertension. This study focused on the early detection of unknown hypertension by screening employees in the hotel and restaurant industry (HRI). 148 HRI employees without hypertension (mean age: 34 years, men: 45%) self-measured their blood pressure during rest and for 24 hours of a normal workday. Individuals with a resting blood pressure ≥ 135/85 mmHg were classified as hypertensive. A further analysis investigated whether the currently applicable thresholds for hypertension during work, leisure, and sleep were exceeded on a working day. At rest, 36% of the study participants suffered from hypertension, which increased to 70% under workload and 46% during leisure time and dropped to 8% during sleep. Normal nocturnal dipping (10–20%) occurred only in 18% of cases; 78% were extreme dippers (>20%). Occupational hypertension screening is a suitable component of preventive healthcare. Resting blood pressure measurement alone is insufficient for the early detection of risk individuals and should be supplemented by 24-hour ambulatory blood pressure monitoring under working conditions. The impact of workload on blood pressure needs to be given more attention in the guidelines.

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Metastatic Renal Cell Carcinoma Presenting as a Solitary Gastric Polyp

A 77-year-old Caucasian man with a remote history of renal cell carcinoma status post nephrectomy 20 years ago underwent an esophagogastroduodenoscopy for persistent dyspepsia. The esophagogastroduodenoscopy showed a 10-mm friable pedunculated polyp in the gastric body (Figure A). Histopathology of the gastric polyp showed ulcerated mucosa containing large atypical cells with increased mitotic activity and abundant eosinophilic cytoplasm in the lamina propria (Figure B). These cells were positive for PAX8 (Figure C), with focal reactivity with CAM5.2 (Figure D) and OSCAR cytokeratin, consistent with metastatic renal cell carcinoma of the stomach.

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Magnetic resonance imaging assessment of the normal knee anterolateral ligament in children and adolescents

Abstract

Objective

To characterize the anterolateral ligament (ALL) in normal knees of pediatric patients by magnetic resonance imaging (MRI) and to establish the age at which it is possible to visualize its presence and whether there are differences between male and female populations.

Materials and methods

MRI scans of patients younger than 18 years were retrospectively evaluated. The exams were performed in 1.5-T scanners. The ALL was characterized dichotomously as visualized or not visualized based on the assessment criteria of this structure in adult patients. The characterization of the ALL was divided according to sex and age.

Results

A total of 363 knee MRI scans were evaluated, 200 from male and 163 from female patients. The ALL was more frequently visualized in coronal sequences. The mean ALL visualization in pediatric patients was 69.4% and was lower in younger patients and higher in patients close to 18 years. It was not possible to visualize the ALL in female patients younger than 7 years or in male patients younger than 6 years. In patients between 17 and 18 years of age, the ALL was visualized in 100% of cases in both sexes.

Conclusions

Visualization of the ALL increased with age in both sexes. Only after age 13 in females and age 15 in males was visualization of the ALL close to 70%; thus, below these ages, we believe that the characterization of this structure with conventional protocols is still imprecise.



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Comparison of thyroid transcription factor-1 expression by two monoclonal antibodies in schwannomas: the chosen clone matters

To the editor:

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High expression of synthesis of cytochrome c oxidase 2 and TP53-induced glycolysis and apoptosis regulator can predict poor prognosis in human lung adenocarcinoma

Synthesis of cytochrome c oxidase 2 (SCO2) and TP53-induced glycolysis and apoptosis regulator (TIGAR) are two p53-mediated proteins that can play a regulatory role in cancer energy metabolism. However, no study has examined the association of SCO2 and TIGAR with the prognosis of patients with lung adenocarcinoma (AC). In our study, the expression of SCO2 and TIGAR proteins in lung AC was detected, and the potential relation to prognosis was evaluated, aiming to take a further view of lung AC progression.

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Comparison of thyroid transcription factor-1 expression by two monoclonal antibodies in Scotchwoman: the chosen clone matters—reply

Dear Editor:

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Genomic Profile of Appendiceal Goblet Cell Carcinoid Is Distinct Compared to Appendiceal Neuroendocrine Tumor and Conventional Adenocarcinoma

Goblet cell carcinoid (GCC) is a rare appendiceal tumor with unique morphologic features that shows glandular and neuroendocrine differentiation on immunohistochemistry. An additional component of adenocarcinoma (AC) can be present (GCC-AC). Both GCC and GCC-AC are staged and treated like AC. The histogenesis and genetic alterations underlying GCC and GCC-AC are unclear. Capture-based next-generation DNA sequencing targeting 479 cancer genes was performed on 19 appendiceal tumors: 4 GCC, 9 GCC-AC, 3 neuroendocrine tumors (NET), and 3AC (2 conventional, 1 mucinous).

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Clinical implication of programmed death-ligand 1 expression in tonsillar squamous cell carcinoma in association with intratumoral heterogeneity, human papillomavirus, and epithelial-to-mesenchymal transition

Programmed death-ligand 1 (PD-L1), essential for immune evasion, is a potential candidate for pathogenesis and therapeutic target of human papillomavirus (HPV)-positive tonsillar squamous cell carcinomas (TSCCs). MET/hepatocyte growth factor (HGF) signaling and transcription factors involved in epithelial-to-mesenchymal transition (EMT) upregulate PD-L1, which can contribute to clinical outcome. Intratumoral heterogeneity of PD-L1 expression is of clinical importance in selection bias due to false-negative patient enrollment.

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Somatic polymerase epsilon mutations as another route leading to loss of DNA MMR protein expression in endometrial carcinoma

To the editor,

https://ift.tt/2GJUYpG

The clinicopathological significance of micropapillary pattern in colorectal cancers

The aim of the present study is to elucidate the clinicopathological significance and prognostic role of micropapillary pattern (MPP) in colorectal cancer (CRC). We investigated the correlation between the presence of MPP and clinicopathological characteristics and prognosis in 266 CRCs. In addition, the clinicopathological significance of MPP in mucin pools was investigated and compared to pure MPP, which is not associated with mucin pools. MPP, regardless of its proportion in the overall tumor, was found in 74 of 266 CRCs (27.8%).

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Frontmatter

Journal Name: Biological Chemistry
Volume: 399
Issue: 5
Pages: i-iv

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Micro-imaging of brain cancer radiotherapy using phase-contrast computed tomography

Experimental X-ray Phase Contrast micro-CT provides ex-vivo 3D representations of post-mortem brain tissue and glioblastoma tumor anatomy of high sensitivity and resolution without the need for extensive sample preparation. This imaging technique proved suitable for a follow-up study of a spatially fractionated radiotherapy technique, X-ray Microbeam Radiation Therapy. We detect 50μm-thick ablations on healthy and tumor tissue, arising from locally-delivered ultra-high-dose X-ray microbeams, as well as calcium and iron accumulation within necrotic tumor tissue.

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Gastric metastasis from pancreatic neuroendocrine tumor



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Secondary gastric involvement of follicular lymphoma



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Linitis plastica in excluded stomach after Roux-en-Y gastric bypass



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Measurement of Mitochondrial Oxygen Consumption in Permeabilized Fibers of Drosophila Using Minimal Amounts of Tissue

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In this paper, a method to measure oxygen consumption using high-resolution respirometry in permeabilized thoraxes of Drosophila is described. This technique requires a minimal amount of tissue compared to the classic mitochondrial isolation technique and the results obtained are more physiologically relevant.

https://ift.tt/2uWofrG

Utilizing High Resolution Ultrasound to Monitor Tumor Onset and Growth in Genetically Engineered Pancreatic Cancer Models

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This article describes the utilization of high-resolution ultrasound in genetically engineered pancreatic cancer mice. The primary aim is to provide a detailed instruction for detection and evaluation of endogenous pancreatic tumors.

https://ift.tt/2qgWpR8

Subarachnoid hemorrhage after transient global amnesia caused by cerebral venous congestion: case report

Transient global amnesia is reported to be caused by cerebral venous congestion. Internal jugular venous flow reversal in particular with the Valsalva maneuver leads to cerebral venous congestion. In addition,...

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Asparagus cochinchinensis stimulates release of nerve growth factor and abrogates oxidative stress in the Tg2576 model for Alzheimer’s disease

Use of multifunctional drugs with neurotrophic supporting and oxidative stress suppressing activity may be considered a therapeutic strategy to protect or repair cellular damage caused during the progression o...

https://ift.tt/2H0Is4j

Neurodevelopmental assessment of HIV-exposed uninfected and early-treated HIV-infected children: study protocol

Sub-Saharan Africa has the highest prevalence of children at risk of not achieving their developmental potential, attributable largely to the human immunodeficiency virus (HIV) pandemic coupled with negative e...

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Bilateral pneumothorax, surgical emphysema and pneumomediastinum in a young male patient following MDMA intake

MDMA (3,4-methylenedioxymethamphetamine) or 'Ecstasy' is an illicit drug frequently used by young people at parties and 'raves'. It is readily available in spite of the fact that it is illegal.1 It is perceived by a lot of young people as being 'harmless', but there have been a few high-profile deaths associated with its use.2 Known side effects of MDMA include hyperthermia, rhabdomyolysis, coagulopathy and cardiac arrhythmias.3 Rarer side effects include surgical emphysema and pneumomediastinum, which have been better described with cocaine abuse.4–6 We present a case of bilateral pneumothorax, surgical emphysema and pneumomediastinum in a young man after taking ecstasy.



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Low-dose warfarin maternal anticoagulation and fetal warfarin syndrome

Fetuses exposed to warfarin during pregnancy are at an increased risk of developing an embryopathy known as fetal warfarin syndrome or warfarin embryopathy. The most consistent anomalies are nasal hypoplasia and stippling of vertebrae or bony epiphyses. Management of pregnant patients on anticoagulation is challenging. Current guidelines suggest the use of warfarin if the therapeutic dose is ≤5 mg/day. We report the case of a newborn with signs of warfarin embryopathy born from a mother anticoagulated with warfarin due to mechanical mitral and aortic heart valves. Warfarin was required at the dose of 5 mg/day and was withheld without medical advice between weeks 8 and 10 with no other anticoagulation. The newborn presented with skeletal abnormalities and a ventricular septal defect that have not required specific treatment during the first year of life. Low-dose warfarin is associated with a lower risk of warfarin-related fetopathy but the risk of embryopathy seems unchanged.



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Pemphigoid gestationis successfully treated with intravenous immunoglobulin

Pemphigoid gestationis (PG), also known as herpes gestationis, is a rare autoimmune blistering disease specific to pregnancy, which usually presents in the second or third trimesters and, in 15%–25% of cases, during the immediate postpartum period.1Although the ethiopathogeny of PG is not fully clarified, most patients develop antibodies against a 180 kDa transmembrane hemidesmosomal protein (BP180; BPAG2; collagen XVII).2 PG has a strong association with human leucocyte antigens DR3 and DR4.3

We report a case of a 29-year-old female patient with PG successfully treated with intravenous immunoglobulin.



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Novel MRI of mediastinal masses: internal differentiation of a thymoma and lymphoma with T1 and T2 mapping

Routine imaging for mediastinal malignancies includes chest X-ray, CT or MRI. T1 and T2 mapping are novel MRI techniques which may have a role in expanding the assessment of internal tumour characteristics. This case report details two middle-aged women who had similar clinical presentations of mediastinal masses of comparable size and appearance when assessed with routine imaging. T1 and T2 maps were acquired on MRI to investigate whether these tumours could be further differentiated prior to surgery. T1 and T2 mapping supported suspicion for which tumour components were solid and cystic, as subsequently confirmed histologically. Furthermore, comparison between the two tumours showed native T1 values differed within the solid components by 37%, correlating to differences in proteinaceous material within the tumour types. This radiological–pathological correlation provides evidence that T1 and T2 mapping has clinical utility in the assessment and differentiation of mediastinal masses.



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Anti-N-methyl-D-aspartate receptor encephalitis relapse in the brainstem

Description

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder involving IgG antibody reaction against NMDAR. It typically develops in women with ovarian teratoma, and its characteristic clinical symptoms include acute behavioural change, psychosis, movement disorder, seizure and autonomic dysfunction. Long-term management in an intensive care unit and immunosuppressive therapy are necessary in most cases, but good prognosis is achieved with appropriate treatment.1 Here, we report a case of anti-NMDAR encephalitis that improved without treatment, but relapsed involving a different brainstem lesion without any symptoms.

A 36-year-old woman was admitted with headache and a single partial seizure 2 weeks after influenza-like fever. At admission, her physical and neurological examination findings as well as routine blood examination results were normal. Cerebrospinal fluid (CSF) analysis revealed a cell count of 163/μL (neutrophil-to-lymphocyte ratio, 15:1) and protein level of 47 mg/dL. MRI showed slight swelling in the limbic system. Meningitis was suspected;...



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Double venous compression due to duplicated inferior vena cava-induced right common iliac vein thrombosis

Venous compression syndromes are caused by extrinsic venous compression of anatomical structures, such as the adjacent arteries and bones. Chronic venous compression and pulsative vibratory arterial pressure accelerate the development of deep vein thrombosis. Herein, we report the first case of double venous compressions due to a duplicated inferior vena cava-induced right-sided common iliac vein thrombosis. The thrombus was induced by left-sided inferior vena cava entrapment and right-sided common iliac vein compression, resembling nutcracker syndrome and May-Thurner syndrome, respectively. Bypass flow of the right inferior vena cava rendered the right lower extremity asymptomatic. Once daily anticoagulation edoxaban was effective. Congenital venous anomalies and bypass formations should be considered when a common iliac vein thrombus without symptoms in the lower extremities is observed, and a lifelong periodical follow-up is mandatory, even after remission.



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Good clinical history scores over extensive workup in unmasking a case of galactorrhoea

The clinical presentation of a young woman with galactorrhoea is described in detail including the history and clinical examination findings. While the patient and her family members feared a serious medical condition which had so far been an obscurity despite a number of investigations, we tried to diagnose the patient starting from the basics, which after a proper history revealed a levosulpiride-induced galactorrhoea. This again lays emphasis on the old adage in medical field that 'a proper history and examination are the key to diagnosis'. There are few reports pertaining to levosulpiride-induced galactorrhoea making it a rare side effect of this drug. We further try to discuss the different causes of galactorrhoea in a young non-pregnant woman which can be encountered in clinical practice.



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Acute lower limb ischaemia secondary to intestinal occlusion

In general, acute lower limb ischaemia is caused by embolic, thrombotic or traumatic phenomena. Here, we describe the case of a 67-year-old woman in an emergency room setting who was initially assessed for paralysis and numbness of her lower left limb. On physical examination, the abdomen was distended and non-compressible. An abdominal AngioScan showed complete occlusion of the left iliac artery by extrinsic compression of the dilated small intestine. After a review of the literature, no case was found describing a lower limb ischaemia by extrinsic vascular compression secondary to a compartment syndrome caused by small bowel obstruction. The treatment of this case required surgical decompression of the abdomen which led to an instantaneous reperfusion of the left leg. Unfortunately, the patient deceased a few hours after the surgery due to haemodynamic deterioration.



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Atypical mycobacteriosis in a poorly compliant patient

Description

Non-tuberculous mycobacteriosis most frequently presents as chronic lung disease.1 Delayed diagnosis or even misdiagnosis occurs due to a great similarity in its clinical presentation to tuberculosis.2 Treatment often seems unprofitable since it is complex and prolonged, poorly tolerated and frequently ineffective in the elimination of the disease.3

The authors present a 68-year-old woman with a history of pulmonary tuberculosis 1 year before, for which she only completed 6 weeks of treatment as well as follow-up, having abandoned both as she believed they went against her culture and religion. She was admitted with productive cough, weakness and weight loss. Blood tests revealed anaemia, thrombocytosis, elevated inflammatory markers, severe hypoalbuminaemia and negative HIV serology. The chest X-ray (figure 1) showed two cavities in the right lung and a consolidation in the left lower lobe. The chest CT scan (figures 2 and 3



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Acute mucocutaneous methotrexate toxicity with marked tissue eosinophilia

Methotrexate toxicity in mucocutaneous areas is usually not associated with tissue eosinophilia. We describe a case of acute methotrexate-induced mucocutaneous erosions with interface dermatitis and eosinophils. A 76-year-old African-American woman with a history of bullous pemphigoid on methotrexate therapy presented with lower extremity cellulitis, developing oral and cutaneous erosions during hospitalization after daily dosage of methotrexate. Shallow circular cutaneous erosions were found on chest, abdomen and limbs. Laboratory results showed pancytopaenia and elevated liver function tests. Skin biopsy revealed irregular acanthotic epidermis with interface dermatitis, individual dyskeratotic cells and superficial perivascular lymphocytic infiltrate with numerous eosinophils. Methotrexate was stopped and leucovorin was administered, leading to improvement. The histopathological changes in acute mucocutaneous toxicity range from pauci-inflammatory erosions with dyskeratotic keratinocytes to interface dermatitis and infrequently seen eosinophils. This case exemplifies that interface dermatitis with a marked eosinophilic infiltrate can be found in the setting of acute mucocutaneous methotrexate toxicity.



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Antithrombotic therapy in patients receiving saphenous vein coronary artery bypass grafts: a protocol for a systematic review and network meta-analysis

Introduction

The current evidence for the prevention of saphenous vein graft failure (SVGF) after coronary artery bypass graft (CABG) surgery consists of direct head-to-head comparison of treatments (including placebo) in randomised-controlled trials (RCTs) and observational studies. However, summarising the evidence using traditional pairwise meta-analyses does not allow the inclusion of data from treatments that have not been compared head to head. Exclusion of such comparisons could impact the precision of pooled estimates in a meta-analysis. Hence, to address the challenge of whether aspirin alone or in addition to another antithrombotic agent is a more effective regimen to improve SVG patency, a network meta-analysis (NMA) is necessary. The objectives of this study are to synthesise the available evidence on antithrombotic agents (or their combination) and estimate the treatment effects among direct and indirect treatment comparisons on SVGF and major adverse cardiovascular events, and to generate a treatment ranking according to their efficacy and safety outcomes.

Methods

We will perform a systematic review of RCTs evaluating antithrombotic agents in patients undergoing CABG. A comprehensive English literature search will be conducted using electronic databases and grey literature resources to identify published and unpublished articles. Two individuals will independently and in duplicate screen potential studies, assess the eligibility of potential studies and extract data. Risk of bias and quality of evidence will also be evaluated independently and in duplicate. We will investigate the data to ensure its suitability for NMA, including adequacy of the outcome data and transitivity of treatment effects. We plan to estimate the pooled direct, indirect and the mixed effects for all antithrombotic agents using a NMA.

Ethics and dissemination

Due to the nature of the study, there are no ethical concerns nor informed consent required. We anticipate that this NMA will be the first to simultaneously assess the relative effects of multiple antithrombotic agents in patients undergoing CABG. The results of this NMA will inform clinicians, patients and guideline developers the best available evidence on comparative effects benefits of antithrombotic agents after CABG while considering the side effect profile to support future clinical decision-making. We will disseminate the results of our systematic review and NMA through a peer-reviewed journal.

PROSPERO registration number

CRD42017065678.



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Danish Centre for Strategic Research in Type 2 Diabetes (DD2) project cohort of newly diagnosed patients with type 2 diabetes: a cohort profile

Purpose

The aim of this article is to provide a detailed description of the ongoing nationwide Danish Centre for Strategic Research in Type 2 Diabetes (DD2) project cohort and biobank. The DD2 cohort continuously enrols newly diagnosed patients with type 2 diabetes (T2D) throughout Denmark. The overall goal of the DD2 project is to establish a large and data-rich T2D cohort that can serve as a platform for exhaustive T2D research including (1) improved genotypic and phenotypic characterisation of T2D, (2) intervention studies of more individualised T2D treatment, (3) pharmacoepidemiological studies and (4) long-term follow-up studies on predictors of T2D complications and prognosis.

Participants

Between 2010 and 2016, 7011 individuals with T2D have been enrolled and assessed at baseline. Information collected include interview data (eg, body weight at age 20 years, physical activity and alcohol consumption), clinical examination data (eg, hip–waist ratio and resting heart rate) and biological samples (whole blood, DNA, plasma and urine) stored at –80°C and currently analysed for a range of biomarkers and genotypes.

Findings to date

Registry linkage has provided extensive supplemental continuous data on glycosylated haemoglobin A, lipids, albuminuria, blood pressure, smoking habits, body mass index, primary care contacts, hospital diagnoses and procedures, medication use, cancer and mortality. Cross-sectional associations between biomarkers, family history, anthropometric and lifestyle measures and presence of complications at baseline have been reported.

Future plans

During 2016, a detailed follow-up questionnaire has been answered by 85% of initial participants, providing follow-up information on baseline variables and on presence of diabetic neuropathy. The DD2 cohort has now been followed for a total of 18 862 person-years, and nested intervention trials and follow-up studies are ongoing. In the future, the cohort will serve as a strong national and international resource for recruiting patients to nested case studies, clinical trials, postmarketing surveillance, large-scale genome studies and follow-up studies of T2D complications.



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Pathways of association between maternal haemoglobin and stillbirth: path-analysis of maternity data from two hospitals in England

Objective

To investigate the mechanisms that link maternal haemoglobin concentration with stillbirth.

Design

A retrospective cohort analysis using anonymised maternity data from two hospitals in England.

Setting

The Royal Wolverhampton NHS Trust and Guy's and St Thomas' NHS Foundation Trust.

Study population

12 636 women with singleton pregnancies ≥24 weeks of gestation giving birth in the two hospitals during 2013–2015.

Method

A conceptual framework of hypothesised pathways through birth weight-for-gestational age and maternal infection including potential confounders and other risk factors was developed and examined using path-analysis. Path-analysis was performed by fitting a set of regression equations using weighted least squares adjusted for mean and variance. Goodness-of-fit indices were estimated.

Main outcome measures

Coefficient of association (β) for relationship between each parameter, and direct, indirect and total effects via the postulated pathways.

Results

The path-model showed a significant adjusted indirect negative effect of maternal haemoglobin on stillbirth mediated via birth weight-for-gestational age (standardised estimate (SE)=–0.01; 95% CI=–0.01 to –0.001; P=0.028). The effect through maternal infection was not significant at P<0.05 (SE=0.001; 95% CI=–0.004 to 0.01; P=0.610). There was a residual direct negative effect of maternal haemoglobin on stillbirth (SE=–0.12; 95% CI –0.23 to –0.02; P=0.020) after accounting for the two pathways. Total indirect SE=–0.004; 95% CI –0.01 to 0.003; P=0.267; total direct and indirect SE=–0.13; 95% CI –0.23 to –0.02; P=0.016. The goodness-of-fit indices showed a good fit between the model and the data.

Conclusion

While some of the influence on risk of stillbirth acts through low birth weight-for-gestational age, the majority does not. Several new mechanisms have been suggested for how haemoglobin may be exerting its influence on the risk of stillbirth possibly involving genetic, epigenetic and/or alternative obstetric and nutritional pathologies, but much more research is needed.



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Should total calcium be adjusted for albumin? A retrospective observational study of laboratory data from central Norway

Objectives

Albumin-adjusted total calcium is often used as a surrogate marker for free calcium to evaluate hypocalcaemia or hypercalcaemia. Many adjustment formulas based on simple linear regression models have been published, and continue to be used in spite of questionable diagnostic accuracy. In the hope of finding a more pure albumin effect on total calcium, we used multiple linear regression models to adjust for other relevant variables. The regression coefficients of albumin were used to construct local adjustment formulas, and we tested whether the diagnostic accuracy was improved compared with previously published formulas and unadjusted calcium.

Design

A retrospective hospital laboratory data study.

Data sources

The local hospital laboratory data system.

Setting

Norway, 2006–2015.

Participants

6549 patients above 2 years of age, where free calcium standardised at pH 7.40, total calcium, creatinine, albumin and phosphate had been analysed in a single blood draw, including hospitalised patients and patients from outpatient clinics and general practice.

Main outcome measures

Diagnostic accuracy by Harrell's c and receiver operating characteristic curve analysis, using free calcium standardised at pH 7.40 as a gold standard, in subgroups with estimated glomerular filtration rate (eGFR) ≥60 or <60 mL/min/1.73 m2.

Results

In the subgroup with eGFR <60 mL/min/1.73 m2, the Harrell's c of unadjusted total calcium (0.801) was significantly larger than those of the local formulas (0.790, p=0.002) and the best formula taken from literature (0.791, p=0.004). In the subgroup with eGFR ≥60 mL/min/1.73 m2, no significant differences were found between these three formulas.

Conclusions

Our study shows that the diagnostic accuracy of unadjusted total calcium is superior to several commonly used adjustment formulas, and we suggest that the use of such formulas should be abandoned in clinical practice. If the clinician does not trust total calcium to reflect the calcium status of the patient, free calcium should be measured.



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Global epidemiology and patterns of cerebral venous thrombosis: a systematic review and meta-analysis protocol

Introduction

Venous thrombosis can affect all veins in the body including cerebral veins, where it causes cerebral venous thrombosis (CVT). CVT is an aetiology of stroke, particularly in children and young adults. Its clinical features vary widely according to the occluded vessel. Data concerning the epidemiology of CVT are scant. This protocol for a systematic review and meta-analysis aims to critically synthesise data concerning prevalence, incidence, risk factors, anatomical patterns, diagnostic and therapeutic delays, and mortality rate of CVT in the global population.

Methods and analysis

MEDLINE, EMBASE and ISI Web of Science databases will be searched for relevant abstracts of studies published between 1 January 1990 and 31 October 2017, without language restriction. After the screening of abstracts, study selection, data extraction and assessment of risk of bias, we will assess studies individually for heterogeneity. Random effects meta-analysis will then be used to pool studies judged to be clinically homogenous. Funnel plot analysis and Egger's test will be used to detect publication bias. Results will be presented according to economic level of the various countries (high-income vs low/middle-income countries).

Ethics and dissemination

Since the current study will be based on published data, ethical approval is not required. This review is expected to provide relevant data to help in evaluating the global burden of CVT. The final report of this study will be published in a peer-reviewed journal.

PROSPERO registration number

CRD42017074266.



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Social relationships and GP use of middle-aged and older adults in Europe: a moderator analysis

Objectives

This paper investigates (1) how social relationships (SRs) relate to the frequency of general practitioner (GP) visits among middle-aged and older adults in Europe, (2) if SRs moderate the association between self-rated health and GP visits, and (3) how the associations vary regarding employment status.

Methods

Data stem from the Survey of Health, Ageing and Retirement in Europe project (wave 4, 56 989 respondents, 50 years or older). GP use was assessed by frequency of contacts with GPs in the last 12 months. Predictors were self-rated health and structural (Social Integration Index (SII), social contact frequency) and functional (emotional closeness) aspects of SR. Regressions were used to measure the associations between GP use and those predictors. Sociodemographic and socioeconomic factors were used as covariates. Additional models were computed with interactions.

Results

Analyses did not reveal significant associations of functional and structural aspects of SR with frequency of GP visits (SII: incidence rate ratio (IRR)=0.99, 95% CI 0.97 to 1.01, social contact frequency: IRR=1.04, 95% CI 1.00 to 1.07, emotional closeness: IRR=1.02, 95% CI 1.00 to 1.04). Moderator analyses showed that 'high social contact frequency people' with better health had more statistically significant GP visits than 'low social contact frequency people' with better health. Furthermore, people with poor health and an emotionally close network showed a significantly higher number of GP visits compared with people with same health, but less close networks. Three-way interaction analyses indicated employment status specific behavioural patterns with regard to SR and GP use, but coefficients were mostly not significant. All in all, the not employed groups showed a higher number of GP visits.

Conclusions

Different indicators of SR showed statistically insignificantly associations with GP visits. Consequently, the relevance of SR may be rated rather low in quantitative terms for investigating GP use behaviour of middle-aged and older adults in Europe. Nevertheless, investigating the two-way and three-way interactions indicated potential inequalities in GP use due to different characteristics of SR accounting for health and employment status.



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Protocol for a mixed methods study of hospital readmissions: sensemaking in Veterans Health Administration healthcare system in the USA

Introduction

Effective delivery of healthcare in complex systems requires managing interdependencies between professions and organisational units. Reducing 30-day hospital readmissions may be one of the most complex tasks that a healthcare system can undertake. We propose that these less than optimal outcomes are related to difficulties managing the complex interdependencies among organisational units and to a lack of effective sensemaking among individuals and organisational units regarding how best to coordinate patient needs.

Methods and analysis

This is a mixed method, multistepped study. We will conduct in-depth qualitative organisational case studies in 10 Veterans Health Administration facilities (6 with improving and 4 with worsening readmission rates), focusing on relationships, sensemaking and improvisation around care transition processes intended to reduce early readmissions. Data will be gathered through multiple methods (eg, chart reviews, surveys, interviews, observations) and analysed using analytic memos, qualitative coding and statistical analyses. We will construct an agent-based model based on those results to explore the influence of sensemaking and specific care transition processes on early readmissions.

Ethics and dissemination

Ethical approval has been obtained through the Institutional Review Board of the University of Texas Health Science Center at San Antonio (approval number: 14–258 hour). We will disseminate our findings in manuscripts in peer-reviewed journals, professional conferences and through short reports back to participating entities and stakeholders.



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Long-term benzodiazepine use in patients taking antidepressants in a public health setting in Brazil: a cross-sectional study

Objective

The aims of the study were to investigate the prevalence of long-term use of benzodiazepines in patients taking antidepressants and to identify the risk factors associated with the prolonged use of benzodiazepines.

Design

Cross-sectional study.

Setting

Public health system in Brazil.

Participants

Outpatients using antidepressants from January 2008 to December 2009 were included. The data were obtained from pharmacy databases and medical records. All individuals in the database were included in the study and were classified into two categories: (1) patients who had not used benzodiazepines combined with antidepressants or had combined the use of antidepressants with benzodiazepines for a short period (up to 4 weeks), and (2) those who used antidepressants plus benzodiazepines for a longer period (more than 4 weeks).

Main outcome measure

The outcome measure is prolonged use of benzodiazepines (more than 4 weeks). We conducted a multivariate analysis to identify the factors associated with prolonged use of benzodiazepines.

Results

Forty per cent of the 870 patients evaluated had prolonged use of benzodiazepines (more than 4 weeks). The risk factors associated with prolonged use were age above 35 years (prevalence ratio (PR): 2.18, 95% CI 1.55 to 3.06, P<0.001), female sex (PR: 1.47, 95% CI 1.07 to 2.02, P=0.019), diagnosis at least 3 years prior (PR: 2.1, 95% CI 1.6 to 2.8, P<0.001), use of selective serotonin reuptake inhibitor antidepressants (PR: 1.7, 95% CI 1.3 to 2.2, P<0.001) and having a prescription from a psychiatrist (PR: 6.5, 95% CI 3.2 to 13.2, P<0.001).

Conclusions

Prolonged use of benzodiazepines occurs more frequently in women, adults diagnosed several years earlier, users of selective serotonin reuptake inhibitor antidepressants and those who received a prescription from a psychiatrist. Education of clinicians, especially with regard to these populations, may decrease the overuse and misuse of benzodiazepines.



https://ift.tt/2IDbHYm

Cause-specific sickness absence trends by occupational class and industrial sector in the context of recent labour market changes: a Finnish panel data study

Objectives

We aimed to provide previously unestablished information on population-based differences in cause-specific sickness absence trends between occupational classes and further between four large industrial sectors within the different occupational classes while controlling for other socioeconomic factors and employment patterns. We focused on the period 2005–2013, during which the labour market underwent large economic and structural changes in many countries.

Design

Register-based panel data study.

Setting

Large representative datasets on Finnish wage earners aged 25–59 years.

Outcome measure

Annual risk of sickness absence (>10 working days) based on repeated logistic regression.

Results

Between 2005 and 2013, the proportion of employees with sickness absence decreased. Occupational class differences in sickness absence trends varied by disease group. Overall, the decrease in absences was smallest among lower non-manual employees. Sickness absence levels were highest in the health and social work sector and in the manufacturing sector within the non-manual and manual classes, respectively. Absences due to musculoskeletal diseases decreased temporarily during the peak of the economic recession in 2009, particularly in the manufacturing sector within the manual class. The decrease in absences due to musculoskeletal diseases was smallest in the trade sector within the lower occupational classes. Overall, education, income and employment patterns partly explained the differences in the absence levels, but not in the trends.

Conclusions

We found a complex interplay between the associations of occupational class and industrial sector with sickness absence trends. During the economic recession, absences due to musculoskeletal diseases decreased temporarily in a segment of wage earners who were known to have been hit hard by the recession. However, the trend differences were not explained by the measured structural changes in the characteristics of the study population. Both occupational class and industrial sector should be taken into account when tackling problems of work disability.



https://ift.tt/2IDbFQe

Risk of perinatal mortality in the first year of midwifery practice in New Zealand: analysis of a retrospective national cohort

Objectives

To determine whether there was an increased risk of perinatal mortality among mothers booked for care with community lead maternity carer (LMC) midwives in their first compared with later years of practice.

Design

Retrospective cohort study using linked national maternity, mortality and workforce data; adjusted analysis using logistic regression.

Setting

New Zealand.

Participants

Women under community LMC midwifery care birthing 2008–2014.

Main outcome measures

Perinatal mortality (stillbirths and neonatal deaths of babies born from 20 weeks' gestation to the 27th day of postnatal life), excluding terminations and deaths associated with congenital abnormalities.

Results

There were 2045 deaths among 344 910 births booked with midwives.

First year of practice midwives cared for women with higher risk of perinatal mortality, including Māori, Pacific, Indian, <20-year-old mothers, nullipara, smokers, women living in socioeconomic deprivation and with high body mass index, than midwives beyond first year of practice.

There was a significant reduction in unadjusted odds of perinatal mortality among women under the care of midwives beyond the first year compared with those within the first year (OR 0.79, 95% CI 0.67 to 0.93) but no significant reduction in risk remained after adjusting for known risk factors, (OR 0.89, 95% CI 0.74 to 1.07).

There was a significant increase in the adjusted odds of perinatal mortality among midwives booking a caseload of 15 or fewer mothers per year (1.34, 1.01 to 1.78) and 16 to 30 (1.25, 1.04 to 1.50) compared with midwives booking 51 to 80.

Conclusions

Findings suggest that the first year of midwifery practice is not associated with an increased risk of perinatal mortality but there is evidence that early career midwives are caring for higher-risk women. These findings suggest inequity of access for higher-risk women to experienced midwives and highlight an opportunity to improve support for vulnerable women and new midwives.



https://ift.tt/2qcqAK7

Role of maternal characteristics and epidural analgesia on caesarean section rate in groups 1 and 3 according to Robsons classification: a cohort study in an Italian university hospital setting

Objective

To investigate the role of maternal characteristics and epidural analgesia (EA) on caesarean section (CS) rates in selected groups by using the Robson 10-Group Classification System (RTGCS).

Design

Cohort study.

Setting

Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario 'A. Gemelli', Rome, Italy.

Patients

A total of 12 098 deliveries in periods I (1998–1999) and II (2010–2011).

Main outcome measures

CS rates in groups 1 and 3 of RTGCS.

Results

In group 1, 1144 (20%) patients were assigned to period I and 1302 (20.4%) to period II, while in group 3, 1587 (27.8%) were assigned to period I and 1502 (23.5%) to period II. CS rates were 16.4% and 23.1% in group 1 and 12.7% and 10.9% in group 3 in periods I and II, respectively. In group 1, significant and independent contributions to CS rate were provided by maternal age (p=0.018; OR 0.95 (95% CI 0.85 to 0.97)), body mass index (BMI) (p=0.022; OR 0.89 (95% CI 0.85 to 0.91)) and EA administration (p=0.037; OR 0.59 (95% CI 0.43 to 0.77)). In group 3, maternal age (p<0.001; OR 0.93 (95% CI 0.89 to 0.96)) and BMI (p=0.023; OR 0.98 (95% CI 0.96 to 0.99)) were found to be significantly associated with CS.

Conclusions

RTGCS is an effective tool for analysing changes in obstetric care, allowing for the recognition of maternal age, BMI and EA administration in the strategic planning for mitigation of CS rates in selected groups.



https://ift.tt/2Et8Sq2

Descriptive epidemiology of changes in weight and weight-related behaviours of Australian children aged 5 years: two population-based cross-sectional studies in 2010 and 2015

Objective

Over the past 10–15 years there has been substantial investment in New South Wales (NSW), Australia, to reduce child obesity through interventions in children aged 0–5 years. We report changes in weight and weight-related behaviours of 5-year-old children.

Design

Cross-sectional surveys conducted in 2010 and 2015.

Setting

NSW schools (2010 n=44; 2015 n=41)

Participants

Australian children in kindergarten (2010 n=1141 and 2015 n=1150).

Outcome measures

Change in anthropometry and indicators of diet, screen time, school travel and awareness of health recommendations. Additionally, we examined 2015 differences in weight-related behaviours by sociodemographic characteristics.

Results

Prevalence of overweight/obesity was 2.1% lower (adjusted OR (AOR) 0.83, 95% CI 0.67 to 1.04) and abdominal obesity 1.7% higher (AOR 1.35, 95% CI 0.93 to 1.98) in 2015 than 2010. Significant improvements in multiple weight-related behaviours were observed among children in the highest tertile of junk food consumption (AOR 0.63, 95% CI 0.50 to 0.80), rewarded for good behaviour with sweets (AOR 0.59, 95% CI 0.47 to 0.74) and had a TV in their bedroom (AOR 0.65, 95% CI 0.43 to 0.96). In 2015, children from low socioeconomic neighbourhoods and non-English-speaking backgrounds were generally less likely to engage in healthy weight-related behaviours than children from high socioeconomic status neighbourhoods and from English-speaking backgrounds. Children in these demographic groups were less likely to eat breakfast daily, have high junk food intake and eat fast food regularly. Children from rural areas tended to have healthier weight-related behaviours than children from urban areas.

Conclusions

There were significant positive changes in 5-year-old children's weight-related behaviours but children from low socioeconomic neighbourhoods and from non-English-speaking backgrounds were more likely to engage in unhealthy weight-related behaviours than children from high socioeconomic neighbourhoods and English-speaking backgrounds. The findings indicate that there is a need to enhance population-level efforts and ensure community programmes are targeted and tailored to meet different subpopulation needs.



https://ift.tt/2qbYNtd

A systematic review of interventions by healthcare professionals to improve management of non-communicable diseases and communicable diseases requiring long-term care in adults who are homeless

Objective

Identify, describe and appraise trials of interventions delivered by healthcare professionals to manage non-communicable diseases (NCDs) and communicable diseases that require long-term care or treatment (LT-CDs), excluding mental health and substance use disorders, in homeless adults.

Design

Systematic review of randomised controlled trials (RCTs), non-RCTs and controlled before–after studies. Interventions characterised using Effective Practice and Organisation of Care (EPOC) taxonomy. Quality assessed using EPOC risk of bias criteria.

Data sources

Database searches (MEDLINE, Embase, PsycINFO, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Applied Social Sciences Index and Abstracts (ASSIA) and Cochrane Central Register of Controlled Trials), hand searching reference lists, citation searches, grey literature and contact with study authors.

Setting

Community.

Participants

Adults (≥18 years) fulfilling European Typology of Homelessness criteria.

Intervention

Delivered by healthcare professionals managing NCD and LT-CDs.

Outcomes

Primary outcome: unscheduled healthcare utilisation. Secondary outcomes: mortality, biological markers of disease control, adherence to treatment, engagement in care, patient satisfaction, knowledge, self-efficacy, quality of life and cost-effectiveness.

Results

11 studies were included (8 RCTs, 2 quasi-experimental and 1 feasibility) involving 9–520 participants (67%–94% male, median age 37–49 years). Ten from USA and one from UK. Studies included various NCDs (n=3); or focused on latent tuberculosis (n=4); HIV (n=2); hepatitis C (n=1) or type 2 diabetes (n=1). All interventions were complex with multiple components. Four described theories underpinning intervention. Three assessed unscheduled healthcare utilisation: none showed consistent reduction in hospitalisation or emergency department attendance. Six assessed adherence to specific treatments, of which four showed improved adherence to latent tuberculosis therapy. Three concerned education case management, all of which improved disease-specific knowledge. No improvements in biological markers of disease (two studies) and none assessed mortality.

Conclusions

Evidence for management of NCD and LT-CDs in homeless adults is sparse. Educational case-management interventions may improve knowledge and medication adherence. Large trials of theory-based interventions are needed, assessing healthcare utilisation and outcomes as well as assessment of biological outcomes and cost-effectiveness.



https://ift.tt/2IwbCFu

Effects of dietary antioxidant vitamins on lung functions according to gender and smoking status in Korea: a population-based cross-sectional study

Objective

Cigarette smoke-induced oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Dietary antioxidants are thought to prevent smoke-induced oxidative damage. The aim of this study was to investigate associations between lung function and the consumption of antioxidant vitamins in Korean adults.

Methods

In total, 21 148 participants from the Korean National Health and Nutrition Examination Survey (2007–2014) were divided into four groups based on smoking history and gender. Multivariate regression models were used to evaluate associations between lung function and intake of dietary antioxidants.

Results

Subjects in the highest intake quintile (Q5) of vitamin A, carotene and vitamin C intake had mean forced expiratory volume in 1 s (FEV1) measurements that were 30 mL, 32 mL and 36 mL higher than those of individuals in the lowest intake quintile (Q1), respectively (p for trend; p=0.008, p=0.010 and p<0.001, respectively). The risks of COPD for male smokers in Q1 increased 7.60-fold (95% CI 5.92 to 9.76), 7.16-fold (95% CI 5.58 to 9.19) and 7.79-fold (95% CI 6.12 to 9.92), for vitamin A, carotene and vitamin C, respectively, compared with those of female non-smokers in Q5. Among patients with COPD, men who smoked >20 pack-years had mean FEV1 measurements that were 192 mL, 149 mL and 177 mL higher than those of patients in Q1 (p for trend; p=0.018, p=0.024 and p=0.043, for vitamin A, carotene and vitamin C, respectively).

Conclusions

These findings indicate that the influence of antioxidant vitamins on lung function depends on gender and smoking status in the Korean COPD population.



https://ift.tt/2JnSZVz

Building motivation to participate in a quality improvement collaborative in NHS hospital trusts in Southeast England: a qualitative participatory evaluation

Objectives

This study explores the barriers and facilitators that impact on the motivation of practitioners to participate in a quality improvement collaborative.

Design

A qualitative and formative evaluation using a participatory approach, the researcher-in-residence model which embraces the concept of 'coproducing' knowledge between researchers and practitioners using a range of research methods such as participant observation, interviews and documentary analysis. The design, creation and application of newly generated evidence are facilitated by the researcher through negotiation and compromise with team members.

Participants

Senior and middle managers, doctors and nurses.

Setting

Two hospitals in Southeast England participating in a Patient Safety Improvement Collaborative and the facilitator (host) of the collaborative, based in Central London.

Results

The evaluation has revealed facilitators and barriers to motivation categorised under two main themes: (1) inherent motivation and (2) factors that influence motivation, interorganisational and intraorganisational features as well as external factors. Facilitators included collaborative 'champions,' individuals who drove the quality improvement agenda at a local level, raising awareness and inspiring colleagues. The collaborative itself acted as a facilitator, promoting shared learning as well as building motivation for participation. A key barrier was the lack of board engagement in the participating National Health Service organisations which may have affected motivation among front-line staff.

Conclusions

Collaboratives maybe an important way of engaging practitioners in quality improvement initiatives. This study highlights that despite a challenging healthcare environment in the UK, there remains motivation among individuals to participate in quality improvement programmes as they recognise that improvement approaches may facilitate positive change in local clinical processes and systems. Collaboratives can harness this individual motivation to facilitate spread and adoption of improvement methodology and build engagement across their membership.



https://ift.tt/2ICO4iz

Cost-effectiveness of insulin pumps compared with multiple daily injections both provided with structured education for adults with type 1 diabetes: a health economic analysis of the Relative Effectiveness of Pumps over Structured Education (REPOSE) randomised controlled trial

Objectives

To assess the long-term cost-effectiveness of insulin pumps and Dose Adjustment for Normal Eating (pumps+DAFNE) compared with multiple daily insulin injections and DAFNE (MDI+DAFNE) for adults with type 1 diabetes mellitus (T1DM) in the UK.

Methods

We undertook a cost–utility analysis using the Sheffield Type 1 Diabetes Policy Model and data from the Relative Effectiveness of Pumps over Structured Education (REPOSE) trial to estimate the lifetime incidence of diabetic complications, intervention-based resource use and associated effects on costs and quality-adjusted life years (QALYs). All economic analyses took a National Health Service and personal social services perspective and discounted costs and QALYs at 3.5% per annum. A probabilistic sensitivity analysis was performed on the base case. Further uncertainties in the cost of pumps and the evidence used to inform the model were explored using scenario analyses.

Setting

Eight diabetes centres in England and Scotland.

Participants

Adults with T1DM who were eligible to receive a structured education course and did not have a strong clinical indication or a preference for a pump.

Intervention

Pumps+DAFNE.

Comparator

MDI+DAFNE.

Main outcome measures

Incremental costs, incremental QALYs gained and incremental cost-effectiveness ratios (ICERs).

Results

Compared with MDI+DAFNE, pumps+DAFNE was associated with an incremental discounted lifetime cost of +£18 853 (95% CI £6175 to £31 645) and a gain in discounted lifetime QALYs of +0.13 (95% CI –0.70 to +0.96). The base case mean ICER was £142 195 per QALY gained. The probability of pump+DAFNE being cost-effective using a cost-effectiveness threshold of £20 000 per QALY gained was 14.0%. All scenario and subgroup analyses examined indicated that the ICER was unlikely to fall below £30 000 per QALY gained.

Conclusions

Our analysis of the REPOSE data suggests that routine use of pumps in adults without an immediate clinical need for a pump, as identified by National Institute for Health and Care Excellence, would not be cost-effective.

Trial registration number

ISRCTN61215213.



https://ift.tt/2EsekcW

Quantitative fibronectin to help decision-making in women with symptoms of preterm labour (QUIDS) part 1: Individual participant data meta-analysis and health economic analysis

Introduction

The aim of the QUIDS study is to develop a decision support tool for the management of women with symptoms and signs of preterm labour, based on a validated prognostic model using quantitative fetal fibronectin (qfFN) concentration, in combination with clinical risk factors.

Methods and analysis

The study will evaluate the Rapid fFN 10Q System (Hologic, Marlborough, Massachusetts) which quantifies fFN in a vaginal swab. In part 1 of the study, we will develop and internally validate a prognostic model using an individual participant data (IPD) meta-analysis of existing studies containing women with symptoms of preterm labour alongside fFN measurements and pregnancy outcome. An economic analysis will be undertaken to assess potential cost-effectiveness of the qfFN prognostic model. The primary endpoint will be the ability of the prognostic model to rule out spontaneous preterm birth within 7 days. Six eligible studies were identified by systematic review of the literature and five agreed to provide their IPD (n=5 studies, 1783 women and 139 events of preterm delivery within 7 days of testing).

Ethics and dissemination

The study is funded by the National Institute of Healthcare Research Health Technology Assessment (HTA 14/32/01). It has been approved by the West of Scotland Research Ethics Committee (16/WS/0068).

PROSPERO registration number

CRD42015027590.

Version

Protocol version 2, date 1 November 2016.



https://ift.tt/2qc11Jn

Elements of integrated care approaches for older people: a review of reviews

Objective

The World Health Organization (WHO) recently proposed an Integrated Care for Older People approach to guide health systems and services in better supporting functional ability of older people. A knowledge gap remains in the key elements of integrated care approaches used in health and social care delivery systems for older populations. The objective of this review was to identify and describe the key elements of integrated care models for elderly people reported in the literature.

Design

Review of reviews using a systematic search method.

Methods

A systematic search was performed in MEDLINE and the Cochrane database in June 2017. Reviews of interventions aimed at care integration at the clinical (micro), organisational/service (meso) or health system (macro) levels for people aged ≥60 years were included. Non-Cochrane reviews published before 2015 were excluded. Reviews were assessed for quality using the Assessment of Multiple Systematic Reviews (AMSTAR) 1 tool.

Results

Fifteen reviews (11 systematic reviews, of which six were Cochrane reviews) were included, representing 219 primary studies. Three reviews (20%) included only randomised controlled trials (RCT), while 10 reviews (65%) included both RCTs and non-RCTs. The region where the largest number of primary studies originated was North America (n=89, 47.6%), followed by Europe (n=60, 32.1%) and Oceania (n=31, 16.6%). Eleven (73%) reviews focused on clinical 'micro' and organisational 'meso' care integration strategies. The most commonly reported elements of integrated care models were multidisciplinary teams, comprehensive assessment and case management. Nurses, physiotherapists, general practitioners and social workers were the most commonly reported service providers. Methodological quality was variable (AMSTAR scores: 1–11). Seven (47%) reviews were scored as high quality (AMSTAR score ≥8).

Conclusion

Evidence of elements of integrated care for older people focuses particularly on micro clinical care integration processes, while there is a relative lack of information regarding the meso organisational and macro system-level care integration strategies.



https://ift.tt/2ErOu90

Transdisciplinary research for impact: protocol for a realist evaluation of the relationship between transdisciplinary research collaboration and knowledge translation

Introduction

Transdisciplinary teams are increasingly regarded as integral to conducting effective research. Similarly, knowledge translation is often seen as a solution to improving the relevance and benefits of health research. Yet, whether, how, for whom and under which circumstances transdisciplinary research influences knowledge translation is undertheorised, which limits its potential impact. The proposed research aims to identify the contexts and mechanisms by which transdisciplinary research contributes to developing shared understandings and behaviours of knowledge translation between team members.

Methods and analysis

Using a longitudinal case-study design approach to realist evaluation, we outline a study protocol examining whether, how, if and for whom transdisciplinary collaboration can impact knowledge translation understandings and behaviours within a 5-year transdisciplinary Centre of Research Excellence. Data are being collected between February 2017 and December 2020 over four rounds of theory development, refinement and testing using interviews, observation, document review and visual elicitation as data sources.

Ethics and dissemination

The Health Research Ethics Committee of the University of Adelaide approved this study. Findings will be communicated with team members at scheduled intervals throughout the study verbally and by means of creative reflective approaches (eg, arts elicitation, journalling). This research will be used to help support optimal team functioning by identifying strategies to support knowledge sharing and communication within and beyond the team to facilitate attainment of research objectives. Academic dissemination will occur through publication and presentations.



https://ift.tt/2JtNcOa

Spatiotemporal heterogeneity and patterning of developing renal blood vessels

Abstract

The kidney vasculature facilitates the excretion of wastes, the dissemination of hormones, and the regulation of blood chemistry. To carry out these diverse functions, the vasculature is regionalized within the kidney and along the nephron. However, when and how endothelial regionalization occurs remains unknown. Here, we examine the developing kidney vasculature to assess its 3-dimensional structure and transcriptional heterogeneity. First, we observe that endothelial cells (ECs) grow coordinately with the kidney bud as early as E10.5, and begin to show signs of specification by E13.5 when the first arteries can be identified. We then focus on how ECs pattern and remodel with respect to the developing nephron and collecting duct epithelia. ECs circumscribe nephron progenitor populations at the distal tips of the ureteric bud (UB) tree and form stereotyped cruciform structures around each tip. Beginning at the renal vesicle (RV) stage, ECs form a continuous plexus around developing nephrons. The endothelial plexus envelops and elaborates with the maturing nephron, becoming preferentially enriched along the early distal tubule. Lastly, we perform transcriptional and immunofluorescent screens to characterize spatiotemporal heterogeneity in the kidney vasculature and identify novel regionally enriched genes. A better understanding of development of the kidney vasculature will help instruct engineering of properly vascularized ex vivo kidneys and evaluate diseased kidneys.



https://ift.tt/2qescSL

Cancers, Vol. 10, Pages 111: Proton Partial Breast Irradiation: Detailed Description of Acute Clinico-Radiologic Effects

Cancers, Vol. 10, Pages 111: Proton Partial Breast Irradiation: Detailed Description of Acute Clinico-Radiologic Effects

Cancers doi: 10.3390/cancers10040111

Authors: Valentina Ovalle Eric A. Strom Simona Shaitelman Karen Hoffman Richard Amos George Perkins Welela Tereffe Benjamin D. Smith Michael Stauder Wendy Woodward

Introduction: Accelerated partial breast irradiation (APBI) with protons results in a very different acute effect profile than standard whole breast irradiation. We reviewed our initial experience with proton APBI and felt that a detailed description of these effects were needed to permit a common tool to compare experience with this developing technology. Methods: Sixty sequential patients treated with proton APBI on a prospective protocol were evaluated and 43 patients with a minimum six-month follow-up underwent detailed photographic and radiologic analysis. The tumorectomy cavity plus an additional 1.5 cm clinical target volume (CTV) was treated with two or three passively-scattered proton beams to a dose of 34 Gy in 10 fractions in one week. Photographs were taken at the end of radiation, at two weeks, six weeks, and every six months thereafter. Mammography was obtained at six months after radiation and annually thereafter. All visual changes were categorized using the smallest meaningful gradations in findings and are demonstrated herein. All treatment-related mammographic findings are reported. Findings: Visual and mammographic findings showed a clear time-dependent relationship and significant variation between individuals. Peak skin reaction occurred at two to six weeks after completion of therapy. At two weeks most patients had either no visible effects and patchy erythema involving &lt;50% of the treated skin (60%). At six weeks most patients had either patchy erythema involving &lt;50% of the overlying skin (33%) or patchy erythema involving &gt;50% of the treated skin (28%). Only one patient developed any moist desquamation. At six months most patients had no visible skin changes (57%) or a small, circular area of mild hyperpigmentation (33%). Mammographic changes seen at six months were regional skin thickening (40%), residual seroma (14%), localized retraction (26%), and fat necrosis (2%). A subcategorized variant on the CTCAE 4.0 was developed to foster granular recording of these findings.



https://ift.tt/2JrMFfV

Sarcomatoid Adenocarcinoma of the Ampulla of Vater

Abstract

Sarcomatoid adenocarcinoma of ampulla of Vater is an extremely rare malignant neoplasm that displays both carcinomatous and sarcomatous component. A 58-year-old woman was admitted to our hospital under the suspicion of an ampulla of Vater cancer. Abdominal computed tomography and endoscopy demonstrated a bulging of ampulla and the biopsy specimen revealed an adenocarcinoma, well differentiated in the background of tubulovillous adenoma. So we performed the pylorus preserving pancreaticoduodenectomy. At postoperative biopsy, the tumor was composed of adenocarcinoma component and sarcomatoid component. Thus, a diagnosis of sarcomatoid adenocarcinoma of ampulla of Vater could be made. Here, we present a case of sarcomatoid adenocarcinoma of ampulla of Vater.



https://ift.tt/2GGxguB

GntR is involved in the expression of virulence in strain Streptococcus suis P1/7

Abstract
Streptococcus suis is a severe zoonotic pathogen, responsible for acute diseases in pigs and human. GntR proteins widely distribute in various bacteria species. In previous study, GntR proteins were reported to be involved in virulence in many pathogens. To investigate the relationship between GntR and S. suis serotype 2, we constructed an isogenic deletion mutant P1/7ΔgntR and an isogenic single-nucleotide substitution mutant P1/7gntR(SC070731), which took strain P1/7 as parent. The results show that the mutants P1/7ΔgntR and P1/7gntR(SC070731) have a stronger ability to tolerate the oxidative stress and reproduce in blood. Moreover, higher fatality rate observed in mice when challenged with P1/7ΔgntR or P1/7gntR(SC070731) compared with that of P1/7. Overall, all results suggest that GntR greatly impacts the virulence of S. suis serotype 2 strain P1/7 and give a new perspective of virulence generation in S. suis.

https://ift.tt/2qbPERp

Neisseria meningitidis disease-associated clones in Amazonas State, Brazil

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https://ift.tt/2uTyE7j

Cancers, Vol. 10, Pages 110: New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

Cancers, Vol. 10, Pages 110: New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

Cancers doi: 10.3390/cancers10040110

Authors: Adrián Montaño Maribel Forero-Castro Darnel Marchena-Mendoza Rocío Benito Jesús María Hernández-Rivas

The identification and study of genetic alterations involved in various signaling pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL) and the application of recent next-generation sequencing (NGS) in the identification of these lesions not only broaden our understanding of the involvement of various genetic alterations in the pathogenesis of the disease but also identify new therapeutic targets for future clinical trials. The present review describes the main deletions, amplifications, sequence mutations, epigenetic lesions, and new structural DNA rearrangements detected by NGS in B-ALL and T-ALL and their clinical importance for therapeutic procedures. We reviewed the molecular basis of pathways including transcriptional regulation, lymphoid differentiation and development, TP53 and the cell cycle, RAS signaling, JAK/STAT, NOTCH, PI3K/AKT/mTOR, Wnt/β-catenin signaling, chromatin structure modifiers, and epigenetic regulators. The implementation of NGS strategies has enabled important mutated genes in each pathway, their associations with the genetic subtypes of ALL, and their outcomes, which will be described further. We also discuss classic and new cryptic DNA rearrangements in ALL identified by mRNA-seq strategies. Novel cooperative abnormalities in ALL could be key prognostic and/or predictive biomarkers for selecting the best frontline treatment and for developing therapies after the first relapse or refractory disease.



https://ift.tt/2Iz2Wyd

Retinal detachment in albinism

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https://ift.tt/2H4jTDK

Disease-Modifying Treatment in Progressive Multiple Sclerosis

Abstract

Purpose of review

Multiple sclerosis (MS) is an immune-mediated disorder that affects the central nervous system (CNS), often first affecting people in early adulthood. Although most MS patients have a relapsing-remitting course (RRMS) at disease onset, a substantial proportion later develop chronic progression, termed secondary progressive MS (SPMS). Approximately 10% of MS patients experience chronic progression from disease onset, termed primary progressive multiple sclerosis (PPMS). Although several disease-modifying treatment (DMT) options exist for relapsing forms of this disease, DMT options are few for progressive MS (PPMS and SPMS). Herein, we strive to define progressive MS, review major clinical trials aimed at progressive MS, and delineate potential strategies in the management of progressive MS.

Recent findings

In 2017, the first DMT for PPMS, the B lymphocyte-depleting monoclonal antibody, ocrelizumab, came to market. Ocrelizumab reduced 12-week confirmed disability progression (CDP) by 24% versus placebo. Siponimod, a selective sphingosine-1-phosphate receptor modulator, reduced 3-month CDP by 21% versus placebo in SPMS. Ibudilast slowed brain atrophy in PPMS and SPMS patients in a multicenter phase 2b study. Smaller early phase studies of alpha-lipoic acid and simvastatin each found slowing of rate of whole brain atrophy in SPMS patients.

Summary

Reasons now exist for optimism in the search for DMTs for progressive MS. It remains a challenge to identify outcome measures that accurately reflect the underlying pathology in progressive MS, which is less inflammatory and more degenerative than RRMS.



https://ift.tt/2GECXce

Development of a blunt chest injury care bundle: an integrative review

Publication date: Available online 7 April 2018
Source:Injury
Author(s): Sarah Kourouche, Thomas Buckley, Belinda Munroe, Kate Curtis
BackgroundBlunt chest injuries (BCI) are associated with high rates of morbidity and mortality. There are many interventions for BCI which may be able to be combined as a care bundle for improved and more consistent outcomes.ObjectiveTo review and integrate the BCI management interventions to inform the development of a BCI care bundle.MethodsA structured search of the literature was conducted to identify studies evaluating interventions for patients with BCI. Databases MEDLINE, CINAHL, PubMed and Scopus were searched from 1990–April 2017. A two-step data extraction process was conducted using pre-defined data fields, including research quality indicators. Each study was appraised using a quality assessment tool, scored for level of evidence, then data collated into categories. Interventions were also assessed using the APEASE criteria then integrated to develop a BCI care bundle.ResultsEighty-one articles were included in the final analysis. Interventions that improved BCI outcomes were grouped into three categories; respiratory intervention, analgesia and surgical intervention. Respiratory interventions included continuous positive airway pressure and high flow nasal oxygen. Analgesia interventions included regular multi-modal analgesia and paravertebral or epidural analgesia. Surgical fixation was supported for use in moderate to severe rib fractures/BCI. Interventions supported by evidence and that met APEASE criteria were combined into a BCI care bundle with four components: respiratory adjuncts, analgesia, complication prevention, and surgical fixation.ConclusionsThe key components of a BCI care bundle are respiratory support, analgesia, complication prevention including chest physiotherapy and surgical fixation.



https://ift.tt/2H14a8q

Loss of histone H3K27me3 identifies a subset of meningiomas with increased risk of recurrence

Abstract

Epigenetic patterns on the level of DNA methylation have already been shown to separate clinically relevant subgroups of meningiomas. We here set out to identify potential prognostic implications of epigenetic modification on the level of histones with focus on H3K27 trimethylation (H3K27me3). H3K27me3 was assessed by immunohistochemistry on 232 meningiomas from 232 patients. In 194 cases, trimethylation was detected in tumor cells. In 25 cases, staining was limited to vessels while all tumor cells were negative. Finally, 13 cases yielded equivocal staining patterns. Reduced abundance of H3K27me3 in cases with staining limited to vessels was confirmed by mass spectrometry on a subset of cases. Lack of staining for H3K27me3 in all tumor cells was significantly associated with more rapid progression (p = 0.009). In line, H3K27me3-negative cases were associated with a DNA methylation pattern of the more aggressive types among the recently introduced DNA methylation groups. Also, NF2 and SUFU mutations were enriched among cases with complete lack of H3K27me3 staining in tumor cells (p < 0.0001 and p = 0.029, respectively). H3K27me3 staining pattern added significant prognostic insight into WHO grade II cases and in the compound subset of WHO grade I and II cases (p = 0.04 and p = 0.007, respectively). However, it did not further stratify within WHO grade III cases. Collectively, these data indicate that epigenetic modifications beyond DNA methylation are involved in the aggressiveness of meningioma. It also suggests that H3K27me3 immunohistochemistry might be a useful adjunct in meningioma diagnostics, particularly for cases with WHO grade II histology or at the borderline between WHO grade I and II.



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