Impacts of perianal disease and faecal incontinence on quality of life and employment in 1092 patients with inflammatory bowel disease

Summary

Background

Patient reported outcomes regarding perianal disease and faecal incontinence in the community-based inflammatory bowel disease population are poorly described.

Aims

To determine the impacts of perianal disease and faecal incontinence on quality of life and employment in inflammatory bowel disease patients.

Methods

For this cross-sectional study, a comprehensive survey was sent out to members of the Dutch National Crohn's and Colitis patient organisation. Validated questionnaires regarding faecal incontinence and active perianal disease were used to estimate its prevalence's. The effect on the quality of life (36-Item Short Form Survey) and on employment status (multivariate binary regression analysis) was assessed in this inflammatory bowel disease population.

Results

A total number of 1092 returned questionnaires (58% responders) were used for analysis; 750 respondents (69%) were female; mean age was 47 years (IQR 35-59). In 621 patients (57%) Crohn's disease, in 422 (39%) ulcerative colitis and in 49 (4%) patients unclassifiable inflammatory bowel disease was self-reported. The 114 patients (10%) with a stoma were excluded for continence related analyses. Faecal incontinence was reported in 555 patients (57%), was comparable between the different inflammatory bowel disease diagnoses and affected all 36-Item Short Form Survey subscales adversely (incontinence vs continence: Physical functioning 75 vs 84, P < 0.0001; Limitations due to physical health 49 vs 63, P < 0.0001; Limitations due to emotional problems 49 vs 64, P < 0.0001; Energy/fatigue 47 vs 53, P < 0.0001; Emotional well-being 71 vs 74, P = 0.005; Social functioning 63 vs 73, P < 0.0001; Pain 66 vs 75, P < 0.0001; General health 41 vs 48, P < 0.0001). Active perianal disease was reported in 39% Crohn's disease, 16% ulcerative colitis (84% fissures) and 20% unclassifiable inflammatory bowel disease patients. Faecal incontinence was more common in patients with perianal disease (67% vs 53%, P = 0.003). When correcting for age, disease duration, inflammatory bowel disease-related surgery and faecal incontinence, active perianal disease was independently affecting employment (OR 0.67; 95% CI 0.50–0.91; P = 0.01).

Conclusions

Faecal incontinence and perianal disease are quality of life determining factors. Faecal incontinence needs more attention among clinicians, and development of new (drug) therapies needs to be focussed on perianal disease.

http://ift.tt/2DgjDM4

Responses are durable for up to 5 years after completion of peginterferon alfa-2a treatment in hepatitis B e antigen-positive patients

Summary

Background

In the large randomised NEPTUNE study, peginterferon alfa-2a 180 μg/wk for 48 weeks produced higher hepatitis B e antigen (HBeAg) seroconversion rates 24 weeks post-treatment (36%) than a lower dose (90 μg/wk) and/or shorter duration (24 weeks) (range 14%-26%).

Aim

To determine seroconversion rates 5 years after completion of treatment in NEPTUNE.

Methods

HBeAg-positive patients who completed 24 weeks' follow-up in NEPTUNE (with peginterferon alfa-2a 90 μg/wk × 24 weeks [group 1]; 180 μg/wk × 24 weeks [2]; 90 μg/wk × 48 weeks [3] or 180 μg/wk × 48 weeks [4]) were followed up.

Results

Three hundred and eighty three of the 544 patients in the original study were enrolled in the long-term follow-up study. Many patients (196 overall; more in groups 1-3 than 4) received nucleos(t)ide analogues or immunomodulators during follow-up, and more patients had missing data at year 5 in groups 2 and 4 (48 weeks, 50/112) than in groups 1 and 3 (24 weeks, 23/103), which confounds the planned per-protocol analysis. HBeAg seroconversion rates in groups 1, 2, 3 and 4 at year 5 were 47.5%, 50.7%, 52.2% and 67.1%, respectively, (odds ratio for group 4 versus 1-3: 2.02; 95% CI 1.21, 3.38), using multiple imputation methods for missing measurements.

Conclusion

Seroconversion rates are durable for up to 5 years after completion of peginterferon alfa-2a therapy and, consistent with NEPTUNE, the results suggest that the licensed regimen (180 μg × 48 weeks) is more efficacious for HBeAg-positive patients than a lower dose and/or shorter treatment duration.

http://ift.tt/2FqJtmo

Pityriasis rosea-like eruption associated with ondansetron use in pregnancy

A 30-year-old pregnant female presented with a 2-week history of pityriasis rosea-like eruption. The rash started 2 days after the patient had started taking ondansetron 8 mg for alleviation of moderate-to-severe nausea and vomiting of pregnancy. Physical examination revealed erythematous papulosquamous lesions characterized by annular scaly margins and a dusky centre over the arms, chest, abdomen, lower back and legs. The rash did not involve the palms, sole or mucous membranes, and no lesions were observed on the lymph nodes. Ondansetron was discontinued. The rash ceased to spread and started to disappear within 2 weeks with full resolution noted after 1 month. Analysis of the case using the Naranjo adverse drug reaction probability scale indicated that ondansetron was the probable cause of the pityriasis rosea-like eruption. This is the first case report of pityriasis rosea related to ondansetron therapy.

http://ift.tt/2FqJfM4

Efficient estimation of personalized biventricular mechanical function employing gradient-based optimization.

Abstract

Individually personalized computational models of heart mechanics can be used to estimate important physiological and clinically-relevant quantities that are difficult, if not impossible, to directly measure in the beating heart. Here we present a novel and efficient framework for creating patient-specific biventricular models using a gradient-based data assimilation method for evaluating regional myocardial contractility and estimating myofiber stress. These simulations can be performed on a regular laptop in less than two hours and produce excellent fit between measured and simulated volume and strain data through the entire cardiac cycle. By applying the framework using data obtained from three healthy human bi-ventricles, we extracted clinically important quantities as well as explored the role of fiber angles on heart function. Our results show that steep fiber angles at the endocardium and epicardium are required to produced simulated motion compatible with measured strain and volume data. We also find that the contraction and subsequent systolic stresses in the right ventricle are signficantly lower than in the left ventricle. Variability of the estimated quantities with respect to both patient data and modeling choices are also found to be low. Because of its high efficiency, this framework may be applicable to modeling of patient specific cardiac mechanics for diagnostic purposes. This article is protected by copyright. All rights reserved.

http://ift.tt/2FmNRCS

Miscarriage induced by adoptive transfer of dendritic cells and invariant natural killer T cells into mice

Abstract

Unexpected fetal loss is one of the common complications of pregnancy; however, the pathogenesis of many miscarriages, particularly those not associated with infections, is unknown. We previously found that activated DEC-205⁺ dendritic cells (DCs) and NK1.1⁺ invariant natural killer T (iNKT) cells are recruited into the myometrium of mice when miscarriage is induced by the intraperitoneal administration of α-galactosylceramide (α-GalCer). Here we demonstrate that the adoptive transfer of DEC-205⁺ bone marrow-derived DCs cocultured with α-GalCer (DEC-205⁺ BMDCs-c/w-α-GalCer) directly induced marked fetal loss by syngeneic pregnant C57BL/6 (B6) mice and allogeneic mice (B6 (♀) × BALB/c (♂)), which was accompanied by the accumulation of activated iNKT cells in the myometrium. Further, the adoptive transfer of NK1.1⁺ iNKT cells obtained from B6 mice injected with α-GalCer facilitated miscarriages in syngeneic Jα18(-/-) (iNKT cell-deficient) mice. These results suggest that DEC-205⁺ DCs and NK1.1⁺ iNKT cells play crucial roles required for the initiation of fetal loss associated with stimulation by glycolipid antigens and sterile inflammation.

This article is protected by copyright. All rights reserved

http://ift.tt/2GaOQ64

Kidney enlargement and multiple liver cyst formation implicate mutations in PKD1/2 in adult sporadic polycystic kidney disease

Distinguishing autosomal dominant polycystic kidney disease (ADPKD) from other inherited renal cystic diseases in patients with adult polycystic kidney disease and no family history is critical for correct treatment and appropriate genetic counseling. However, for patients with no family history, there are no definitive imaging findings that provide an unequivocal ADPKD diagnosis. We analyzed 53 adult polycystic kidney disease patients with no family history. Comprehensive genetic testing was performed using capture-based next-generation sequencing for 69 genes currently known to cause hereditary renal cystic diseases including ADPKD. Through our analysis, 32 patients had PKD1 or PKD2 mutations. Additionally, three patients with disease-causing mutations in NPHP4, PKHD1, and OFD1 were diagnosed with an inherited renal cystic disease other than ADPKD. In patients with PKD1 or PKD2 mutations, the prevalence of polycystic liver disease, defined as more than 20 liver cysts, was significantly higher (71.9% versus 33.3%, p = 0.006), total kidney volume was significantly increased (median, 1580.7 ml versus 791.0 ml, p = 0.027) and mean arterial pressure was significantly higher (median, 98 mmHg versus 91 mmHg, p = 0.012). The genetic screening approach and clinical features described here are potentially beneficial for optimal management of adult sporadic polycystic kidney disease patients.

http://ift.tt/2FofzPJ

BRAF and EGFR inhibitors synergize to increase cytotoxic effects and decrease stem cell capacities in BRAF(V600E)-mutant colorectal cancer cells

Abstract

Mutations in the oncogene BRAF(V600E) are found in ~10% of colorectal cancers (CRCs) and are associated with poor prognosis. However, BRAF(V600E) has a limited response to the small-molecule drug, vemurafenib, a BRAF inhibitor, and BRAF inhibition is thought to cause a feedback activation of EGFR signaling that supports continued proliferation. In this study, we explored the effect of combined use of dabrafenib, a BRAF inhibitor, and cetuximab, an EGFR inhibitor, on BRAF(V600E)-mutant CRC stem cells and its possible mechanisms. Through cell viability analysis, flow cytometry, sphere forming, and western blot analysis, we found that the dabrafenib can synergize with cetuximab to reduce cell viability, induce enhanced apoptotic rates and cell cycle arrest in BRAF(V600E)-mutant HT-29 cells and inhibits stem cell capacities. Further, western blot analysis revealed that PTEN/Src/c-Myc pathway is possibly involved in the synergism between dabrafenib and cetuximab. Overall, our study shows that the combination of dabrafenib and cetuximab results in increased antitumor activity and decreased stem cell capacities in BRAF(V600E)-mutant CRC cells.

http://ift.tt/2Ido1it

PKC inhibition of sotrastaurin has antitumor activity in diffuse large B-cell lymphoma via regulating the expression of MCT-1

Abstract

MCT-1 (multiple copies in T-cell lymphoma-1), a novel oncogene, was originally identified in T-cell lymphoma. A recent study has demonstrated that MCT-1 is highly expressed in 85% of diffuse large B-cell lymphomas (DLBCL). PKC (protein kinase C) plays an essential role in signal transduction for multiple biologically active substances for activating cellular functions and proliferation. In this study, we found that the mRNA and protein expression levels of MCT-1 were visibly decreased after knocking down PKC by siRNA in SUDHL-4 and OCI-LY8 DLBCL cell lines. A selective PKC inhibitor, sotrastaurin, effectively inhibited cell proliferation and induced cell apoptosis in a dose- and time-dependent manner. Meanwhile, we also observed that the cell cycle was arrested in the G1 phase in sotrastaurin-treated cells. In addition, MCT-1 was down-regulated in the sotrastaurin treatment group in vivo. Furthermore, we demonstrated that the PKC inhibitor sotrastaurin induced cell apoptosis and cell cycle arrest in DLBCL cells potentially through regulating the expression of MCT-1. Our data suggest that targeting PKC may be a potential therapeutic approach for lymphomas and related malignancies that exhibit high levels of MCT-1 protein.

http://ift.tt/2Dac0q9

Long non-coding RNA CASC2 inhibits tumorigenesis via the miR-181a/PLXNC1 axis in melanoma

Abstract

Melanoma is the most malignant and aggressive form of skin carcinoma originating in the pigment-producing melanocytes. In this study, to further investigate the molecular mechanisms of the development and progression of melanoma, we explored the impacts of long non-coding RNA (lncRNA) CASC2 on melanoma cell functions. Microarray analysis was carried out to identify the expression of lncRNA CASC2 in melanoma cells. MiR-181a was predicted as a sponging target of CASC2 by miRcode, while the 3′-UTR of Plexin C1 (PLXNC1) was a potential target of miR-181a according to the TargetScan database. The correlation among CASC2, miR-181a, and PLXNC1 was verified by dual luciferase reporter assay and qRT-PCR. After manipulation of CASC2, miR-181a and PLXNC1 expression with transfection in A375 and M14 cells, cell viability, apoptosis, and invasive ability were evaluated using CCK-8, flow cytometry and Transwell assays, respectively. A low expression of CASC2 was detected in melanoma tissues and cells. Dual luciferase reporting assay confirmed that miR-181a targeted the 3′-UTR of PLXNC1. Furthermore, CASC2 could efficiently sponge miR-181a, thereby facilitating the expression of PLXNC1. Up-regulation of CASC2 suppressed the cell proliferation and invasion, but induced the apoptosis of melanoma cells. Our results demonstrated that lncRNA CASC2 can promote PLXNC1 expression by sponging miR-181a, thereby inhibiting the proliferation and invasion of melanoma cells, indicating that lncRNA CASC2 functions via the miR-181a/PLXNC1 axis in melanoma.

http://ift.tt/2IdnWvb

Correction: Protocol for Compass: a randomised controlled trial of primary HPV testing versus cytology screening for cervical cancer in HPV-unvaccinated and vaccinated women aged 25-69 years living in Australia

Canfell K, Saville M, Caruana M, et al. Protocol for compass: a randomised controlled trial of primary HPV testing versus cytology screening for cervical cancer in HPV-unvaccinated and vaccinated women aged 25–69 years living in Australia. BMJ Open 2018;8:e016700. doi: 10.1136/bmjopen-2017-016700.

Professor Suzanne Garland was missed out of the original Acknowledgements statement. The Acknowledgements section should read:

Acknowledgments We would like to thank the following associate investigators for their contribution to the Compass trial: Mr David H Wrede, Dr Jeff Tan, Dr Siobhan Bourke, Dr Lara Roeske, Dr Jane Collins, Sandy Anderson and Associate Professor Sally Lord. We would also like to acknowledge the following Scientific Advisory Committee members: Professor Bruce Armstrong, Professor Suzanne Garland, Professor Jonathan Carter, Associate Professor Rachel Skinner, Dr Deborah Bateson, Professor Andrew Grulich, Dr Eduardo Franco, Ms Bridget Whelan (sadly deceased), Associate Professor Annabelle Farnsworth and Ms Susan Taylor. In addition, we would like...

http://ift.tt/2p1E5Lz

The role of clothing in participation of persons with a physical disability: a scoping review protocol

Introduction

Clothing is an important aspect of nearly all human societies from performing social and cultural functions to indicating social status, a form of protection and a way for self-expression. It can help or hinder the ability to fulfil everyday activities and social roles and with the rising industry of wearable technologies, smart textiles are adding health-monitoring functions to clothing. The influence that clothing can have on the life of someone with a physical disability is significant, and further research is needed to understand it better. To achieve this, a scoping review will be performed with the aim of understanding the role of clothing in participation (ie, at home, in the community, etc) of individuals with a physical disability. This article presents the protocol and procedure to be adopted.

Methods and analysis

An in-depth iterative analysis of the scientific literature from six databases (MEDLINE, Embase, CINAHL, Scopus, PsycINFO and ERIC) as well as a hand search of grey literature and reference lists will be performed. After an abstract and full-text review of references by three reviewers independently, data from the selected articles will be tabulated and synthesised with a qualitative and quantitative approach using the International Classification of Functioning, Disability and Health as a unifying conceptual framework. A multidisciplinary consultation group of experts from various stakeholder groups will be involved in multiple steps to ensure validation and relevance of the data.

Ethics and dissemination

As this is a review involving analysis of data available in the public domain and does not involve human participants, ethical approval was not required. Results will be presented in a co-constructed format with the expert consultation group to ensure validity and maximise its practicality moving forward. Our dissemination plan includes peer-reviewed publications, presentations and stakeholder meetings.

http://ift.tt/2FCiT92

Effects of family group conferences among high-risk patients of chronic disability and their significant others: study protocol for a multicentre controlled trial

Introduction

Many patients and family members experience a large gap between the protected environment during inpatient medical rehabilitation and life in the community after discharge. They feel insufficiently prepared to cope with the consequences of their disability in daily life. This study protocol describes the design measuring the effectiveness and implementation of family group conferences on the empowerment of patients with a high risk of chronic disability and their significant others.

Methods and analysis

A multicentre controlled trial will be carried out in 12 rehabilitation centres in the Netherlands. A total of 328 clinically admitted patients will participate (≥18 years, diagnosed with acquired brain injury, spinal cord injury or leg amputation), and their significant others will be included. During three family group conferences, supported by the social worker, the patient, significant other and their social network will be stimulated in collaboration, to set up participation goals, determine the needed help and make a concrete action plan. Self-reported questionnaires will be collected at baseline, clinical discharge, and 3 months and 6 months following clinical discharge. Empowerment as the primary outcome is operationalised as self-efficacy and participation. Secondary outcome measures are psychological (eg, coping, neuroticism) and environmental (eg, family functioning, social support) factors. This is the first controlled trial evaluating the effectiveness of family group conferences in rehabilitation medicine among adult patients and their significant others, providing us with knowledge in improving rehabilitation care.

Ethics and dissemination

This study has been approved by the Medical Ethics Committee of the University Medical Center Utrecht (number 15–617/C). The results will be published in peer-reviewed journals and presented in local, national and international conferences.

Trial registration number

NTR5742; Pre-results.

http://ift.tt/2Hk09sn

Identifying priority policy issues and health system research questions associated with recovery outcomes for burns survivors in India: a qualitative inquiry

Objectives

This study aimed to identify priority policy issues and health system research questions associated with recovery outcomes for burns survivors in India.

Design

Qualitative inquiry; data were collected through semistructured in-depth interviews and focus group discussions.

Setting

Nine sites in urban and rural settings across India, through primary, secondary and tertiary health facilities.

Participants

Healthcare providers, key informants, burns survivors and/or their carers.

Results

Participants acknowledged the challenges of burns care and recovery, and identified the need for prolonged rehabilitation. Challenges identified included poor communication between healthcare providers and survivors, limited rehabilitation services, difficulties with transportation to health facility and high cost associated with burns care. Burns survivors and healthcare providers identified the stigma attached with burns as the biggest challenge within the healthcare system, as well as in the community. Systems barriers (eg, limited infrastructure and human resources), lack of economic and social support, and poor understanding of recovery and rehabilitation were identified as major barriers to recovery.

Conclusions

Though further research is needed for addressing gaps in data, strengthening of health systems can enable providers to address issues such as developing/providing, protocols, capacity building, effective coordination between key organisations and referral networks.

http://ift.tt/2FFLsCG

Agreement between electronic and paper Epworth Sleepiness Scale responses in obstructive sleep apnoea: secondary analysis of a randomised controlled trial undertaken in a specialised tertiary care clinic

Objectives

Originally developed as a paper questionnaire, the electronic Epworth Sleepiness Scale (ESS) is widely used in sleep clinics and sleep population research. Despite potential differences between computer-based and conventional questionnaire delivery, studies have not evaluated the agreement between electronic and paper versions of the ESS. Given the widespread use of the ESS, a bias between results would present considerable data concerns. Thus, the aim of this study was to examine agreement between electronic and paper ESS responses in obstructive sleep apnoea (OSA).

Design

We undertook a secondary analysis of baseline data from a randomised controlled trial (ANZCTR: ACTRN12611000847910).

Setting

Data were collected in a tertiary sleep research laboratory located in Sydney, Australia.

Participants

Data were analysed from 112 adult patients with OSA.

Measurements

Patients were given the English version of the ESS as part of a battery of sleep laboratory questionnaires. They completed electronic and subsequently paper ESS questionnaires on the same day.

Results

We found no significant difference between electronic and paper ESS questionnaires (mean=0.1, SD=2.1, 95% CI –0.3 to 0.5, P=0.57) or heteroscedasticity. There was no evidence of bias along the range of the measure. 95% limits of agreement at 4.3 and –4.1 were comparable with previous data.

Conclusions

We found no evidence of bias between electronic and paper ESS questionnaires in this sample of patients with OSA, as the two formats displayed sufficient agreement to be clinically comparable. Regardless of severity, patients reported the same level of daytime sleepiness with the same level of accuracy across both measures.

Trial registration number

ACTRN12611000847910; Pre-results.

http://ift.tt/2p0TOdJ

Prognostic significance of autoantibodies for idiopathic pulmonary fibrosis: protocol for a systematic review

Introduction

Idiopathic pulmonary fibrosis(IPF) is chronic fibrosing interstitial pneumonia of unknown aetiology. IPF is diagnosed based on the exclusion of known causes such as connective tissue diseases(CTDs). However, some patients fail to meet defined CTD criteria regardless of an implication of immunological involvement and these cases were described in a variety of terms. The classification criteria of this clinical entity consist of a combination of clinical, serological and morphological findings and it is reported to be distinct from IPF. However, the significance of the sole presence of autoantibodies complicated with IPF is still unknown. Therefore, this systematic review aims to clarify the significance of autoantibodies complicated with IPF.

Methods and analysis

IPF with any autoantibody associated with CTDs is eligible for the review. Primary outcomes are all-cause mortality and pulmonary-cause mortality, while secondary outcomes include a progression of the disease, a deterioration of health-related quality of life and the development of a defined CTD. Primary studies of any type except a case report are included. Two reviewers search four electronic databases such as Medline, EMBASE, Science Citation Index Expanded and Google Scholar from each inception through 1 February 2018 and extract data independently. A risk of bias in individual studies is assessed by the Quality in Prognostic Studies tool. Meta-analysis is sought to be conducted if three or more studies report an outcome for a specific autoantibody with the same statistics. If it is inappropriate to combine data due to substantial heterogeneity, the result is reported qualitatively. Subgroup and sensitivity analyses are considered to identify the source of heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation method is applied to evaluate the evidence level of the result.

Ethics and dissemination

There is no concerning ethical issue. The result will be sought for publication.

PROSPERO registration number

CRD42017077336.

http://ift.tt/2FGRqmy

What integrated care means from an older persons perspective? A scoping review protocol

Introduction

According to the 2013 WHO Global Forum on Innovation for Ageing Populations, disabilities and morbidities associated with ageing could be minimised by accessing preventive care. One way of improving the management of multimorbidity in the older population is through the provision of 'integrated care'. Although integrated care means different things to different people, it typically symbolises continuity in care, thus preventing older patients' from falling through gaps in the health care system. Many initiatives have attempted to improve the integration of care; however, these are typically designed from a particular policy or system perspective. Relatively little is known about patient expectations and experiences of integrated care, which is vital for developing and implementing better models of care. The proposed scoping review aims to map literature on older patients'' views, expectations, experiences and perspectives of integrated care.

Methods and analysis

Multiple electronic databases including PubMed, Web of Science, Embase, PsychInfo, Google Scholar, Cochrane Library, CINAHL and ProQuest Dissertations will be searched for appropriate articles between August and December 2017. Reference lists of selected articles will also be searched for similar articles. Two experienced researchers will conduct an initial search of the literature to identify relevant articles. Abstracts of the identified articles will be reviewed collectively by two researchers to identify potential further studies. Full texts of the potential studies will be sourced and screened for the inclusion criteria. Appropriate qualitative and quantitative methods will be used to extract data from each included study.

Ethics and dissemination

The scoping review will synthesise findings from studies reporting on patients' views and expectations of integrated care. This review expects to find information relating to facilitators and barriers of integrated care from an older person's perspective. The findings from the review will be applied when working with stakeholders representing older people, healthcare, aged care and community providers, researchers and policy makers to develop and evaluate a more locally tailored and person-centred approach to integrated care.

http://ift.tt/2HjLo8C

Correction: Variations in childbirth interventions in high-income countries: protocol for a multinational cross-sectional study

Seijmonsbergen-Schermers A, de Jonge A, van den Akker T, et al. Variations in childbirth interventions in high-income countries: protocol for a multinational cross-sectional study. BMJ Open 2018;8:e017993. doi: 10.1136/bmjopen-2017-017993.

The author order is incorrect in the article. The correct author order should be:

Anna Seijmonsbergen-Schermers, Thomas van den Akker, Katrien Beeckman, Annick Bogaerts, Monalisa Barros, Patricia Janssen, Lorena Binfa, Eva Rydahl, Lucy Frith, Mechthild M Gross, Berglind Hálfdánsdóttir, Deirdre Daly, Jean Calleja-Agius, Patricia Gillen, Anne Britt Vika Nilsen, Eugene Declercq, Ank de Jonge.

http://ift.tt/2FEZvbx

Using HTA and guideline development as a tool for research priority setting the NICE way: reducing research waste by identifying the right research to fund.

Background

The National Institute for Health and Care Excellence (NICE) was established in 1999 and provides national guidance and advice to improve health and social care. Several steps in the research cycle have been identified that can support the reduction of waste that occurs in biomedical research. The first step in the process is ensuring appropriate research priority setting occurs so only the questions that are needed to fill existing gaps in the evidence are funded. This paper summarises the research priority setting processes at NICE.

Methods

NICE uses its guidance production processes to identify and prioritise research questions through systematic reviews, economic analyses and stakeholder consultations and then highlights those priorities by engagement with the research community. NICE also highlights its methodological areas for research to ensure the appropriate development and growth of the evidence landscape.

Results

NICE has prioritised research questions through its guidance production and methodological work and has successfully had several research products funded through the National Institute for Health Research and Medical Research Council. This paper summarises those activities and results.

Conclusions

This activity of NICE therefore reduces research waste by ensuring that the research it recommends has been systematically prioritised through evidence reviews and stakeholder input.

http://ift.tt/2HjiPIp

A tailored strategy for designing the Walk-Copenhagen (WALK-Cph) intervention to increase mobility in hospitalised older medical patients: a protocol for the qualitative part of the WALK-Cph project

Introduction

Older medical patients (>65 years) represent 54% of the admissions to Danish medical and emergency departments. Acute admissions and bed-rest during hospitalisation are independent risk factors for death and dependency in older patients. Even short hospitalisations are associated with increased dependency in activities of daily living after discharge. Interventions that increase mobility during hospitalisation are therefore important. The purpose of this protocol is to describe the intervention design of the WALK-Copenhagen project, aimed at increasing 24 hours mobility in older medical patients during acute hospitalisations and following discharge.

Methods and analysis

This study is based on ethnographic fieldwork and interviews. Workshops are used to develop and co-design the intervention in collaboration with key stakeholders (patients, relatives, health professionals and researchers). The theory of cultural learning processes, and the cultural historical activity theory will be used to help us understand the interaction between health professionals, structures and objects in relation to mobility in the medical departments.

Ethics and dissemination

The project will adhere to the directives of the Helsinki Declaration. Ethical approval was not required for the study since formal ethical approval is not mandatory for studies that do not involve biomedical issues (I-Suite no: 05078) according to Danish law. Informed consent was obtained for all participants. The results will be disseminated to health professionals, managers, patients and relatives, who will be invited to afternoon meetings where the project will be discussed. The results will be published in peer-reviewed scientific journals and presented at scientific conferences.

http://ift.tt/2FF7wx2

Feasibility of real-time capture of routine clinical data in the electronic health record: a hospital-based, observational service-evaluation study

Objectives

The electronic health record (EHR) is underused in the hospital setting. The aim of this service evaluation study was to respond to National Health Service (NHS) Digital's ambition for a paperless NHS by capturing routinely collected cardiac outpatient data in the EHR to populate summary patient reports and provide a resource for audit and research.

Design

A PowerForm template was developed within the Cerner EHR, for real-time entry of routine clinical data by clinicians attending a cardiac outpatient clinic. Data captured within the PowerForm automatically populated a SmartTemplate to generate a view-only report that was immediately available for the patient and for electronic transmission to the referring general practitioner (GP).

Results

During the first 8 months, the PowerForm template was used in 61% (360/594) of consecutive outpatient referrals increasing from 42% to 77% during the course of the study. Structured patient reports were available for immediate sharing with the referring GP using Cerner Health Information Exchange technology while electronic transmission was successfully developed in a substudy of 64 cases, with direct delivery by the NHS Data Transfer Service in 29 cases and NHS mail in the remainder. In feedback, the report's immediate availability was considered very or extremely important by >80% of the patients and GPs who were surveyed. Both groups reported preference of the patient report to the conventional typed letter. Deidentified template data for all 360 patients were successfully captured within the Trust system, confirming availability of these routinely collected outpatient data for audit and research.

Conclusion

Electronic template development tailored to the requirements of a specialist outpatient clinic facilitates capture of routinely collected data within the Cerner EHR. These data can be made available for audit and research. They can also be used to enhance communication by populating structured reports for immediate delivery to patients and GPs.

http://ift.tt/2Hmgfld

Cognitive-behavioural therapy (CBT) for renal fatigue (BReF): a feasibility randomised-controlled trial of CBT for the management of fatigue in haemodialysis (HD) patients

Introduction

Fatigue is one of the most common and disabling symptoms in end-stage kidney disease, particularly among in-centre haemodialysis patients. This two-arm parallel group feasibility randomised controlled trial will determine whether a fully powered efficacy trial is achievable by examining the feasibility of recruitment, acceptability and potential benefits of a cognitive-behavioural therapy (CBT)-based intervention for fatigue among in-centre haemodialysis patients.

Methods

We aim to recruit 40 adult patients undergoing in-centre haemodialysis at secondary care outpatient dialysis units, who meet clinical levels of fatigue. Patients will be randomised individually (using a 1:1 ratio) to either a 4–6 weeks' CBT-based intervention (intervention arm) or to a waiting-list control (control arm). The primary feasibility outcomes include descriptive data on numbers within each recruiting centre meeting eligibility criteria, rates of recruitment, numbers retained postrandomisation and treatment adherence. To assess the potential benefits of the cognitive-behavioural therapy for renal fatigue intervention, secondary self-report outcomes include measures of fatigue severity (Chalder Fatigue Questionnaire), fatigue-related functional impairment (Work and Social Adjustment Scale), sleep quality (Pittsburgh Sleep Quality Index), depression (Patient Health Questionnaire-9) and anxiety (Generalised Anxiety Disorder-7). Changes in fatigue perceptions (Brief Illness Perception Questionnaire), cognitive and behavioural responses to fatigue (Cognitive and Behavioural Responses to Symptoms Questionnaire), sleep hygiene behaviours (Sleep Hygiene Index) and physical activity (International Physical Activity Questionnaire–short form) will also be explored. These self-report measures will be collected at baseline and 3 months postrandomisation. Nested qualitative interviews will be conducted postintervention to explore the acceptability of the intervention and identify any areas in need of improvement. The statistician and assessor will be blinded to treatment allocation.

Ethics and dissemination

A National Health Service (NHS) Research Ethics Committee approved the study. Any amendments to the protocol will be submitted to the NHS Committee and study sponsor.

Trial registration number

ISRCTN91238019;Pre-results.

http://ift.tt/2FzHNGt

Long-term clinical parameters after switching to nocturnal haemodialysis: a Dutch propensity-score-matched cohort study comparing patients on nocturnal haemodialysis with patients on three-times-a-week haemodialysis/haemodiafiltration

Objectives

Nocturnal haemodialysis (NHD), characterised by 8-hour sessions ≥3 times a week, is known to improve clinical parameters in the short term compared with conventional-schedule haemodialysis (HD), generally 3x3.5–4 hours a week. We studied long-term effects of NHD and used patients on conventional HD/haemodiafiltration (HDF) as controls.

Design

Four-year prospective follow-up of patients who switched to NHD; we compared patients with patients on HD/HDF using propensity score matching.

Setting

28 Dutch dialysis centres.

Participants

We included 159 patients starting with NHD any time since 2004, aged 56.7±12.9 years, with median dialysis vintage 2.3 (0.9–5.1) years. We propensity-score matched 100 patients on NHD to 100 on HD/HDF.

Primary and secondary outcome measures

Control of hypertension (predialysis blood pressure, number of antihypertensives), phosphate (phosphate, number of phosphate binders), nutritional status and inflammation (albumin, C reactive protein and postdialysis weight) and anaemia (erythropoiesis-stimulating agent (ESA) resistance).

Results

Switching to NHD was associated with a non-significant reduction of antihypertensives compared with HD/HDF (OR <2 types 2.17, 95% CI 0.86 to 5.50, P=0.11); and a prolonged lower need for phosphate binders (OR <2 types 1.83, 95% CI 1.10 to 3.03, P=0.02). NHD was not associated with significant changes in blood pressure or phosphate. NHD was associated with significantly higher albumin over time compared with HD/HDF (0.70 g/L/year, 95% CI 0.10 to 1.30, P=0.02). ESA resistance decreased significantly in NHD compared with HD/HDF, resulting in a 33% lower ESA dose in the long term.

Conclusions

After switching to NHD, the lower need for antihypertensives, phosphate binders and ESA persists for at least 4 years. These sustained improvements in NHD contrast significantly with the course of these parameters during continued treatment with conventional-schedule HD and HDF. NHD provides an optimal form of dialysis, also suitable for patients expected to have a long waiting time for transplantation or those convicted to indefinite dialysis.

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Correction: Qualitative meta-synthesis of barriers and facilitators that influence the implementation of community pharmacy services: perspectives of patients, nurses and general medical practitioners

Hossain LN, Fernandez-Llimos F, Luckett T, et al. Qualitative meta-synthesis of barriers and facilitators that influence the implementation of community pharmacy services: perspectives of patients, nurses and general medical practitioners. BMJ Open 2017;7:e015471. doi: 10.1136/bmjopen-2016-015471

In figure 1, the number below 'Records after duplicates removed' should be 243 not 278. The corrected figure is shown below.

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Perspectives of healthcare providers on the nutritional management of patients on haemodialysis in Australia: an interview study

Objective

To describe the perspectives of healthcare providers on the nutritional management of patients on haemodialysis, which may inform strategies for improving patient-centred nutritional care.

Design

Face-to-face semistructured interviews were conducted until data saturation, and thematic analysis based on principles of grounded theory.

Setting

21 haemodialysis centres across Australia.

Participants

42 haemodialysis clinicians (nephrologists and nephrology trainees (15), nurses (12) and dietitians (15)) were purposively sampled to obtain a range of demographic characteristics and clinical experiences.

Results

Six themes were identified: responding to changing clinical status (individualising strategies to patient needs, prioritising acute events, adapting guidelines), integrating patient circumstances (assimilating life priorities, access and affordability), delineating specialty roles in collaborative structures (shared and cohesive care, pivotal role of dietary expertise, facilitating access to nutritional care, perpetuating conflicting advice and patient confusion, devaluing nutritional specialty), empowerment for behaviour change (enabling comprehension of complexities, building autonomy and ownership, developing self-efficacy through engagement, tailoring self-management strategies), initiating and sustaining motivation (encountering motivational hurdles, empathy for confronting life changes, fostering non-judgemental relationships, emphasising symptomatic and tangible benefits, harnessing support networks), and organisational and staffing barriers (staffing shortfalls, readdressing system inefficiencies).

Conclusions

Organisational support with collaborative multidisciplinary teams and individualised patient care were seen as necessary for developing positive patient–clinician relationships, delivering consistent nutrition advice, and building and sustaining patient motivation to enable change in dietary behaviour. Improving service delivery and developing and delivering targeted, multifaceted self-management interventions may enhance current nutritional management of patients on haemodialysis.

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Correction: Fabry disease due to D313Y and novel GLA mutations

Koulousios K, Stylianou K, Pateinakis P, et al. Fabry disease due to D313Y and novel GLA mutations. BMJ Open 2017;7:e017098. doi:10.1136/bmjopen-2017-017098.

The footnotes should include the following statement:

Patient consent Written consent to publish these case reports has been obtained from the patient or next of kin.

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Correction: Understanding frailty: a qualitative study of European healthcare policy-makers approaches to frailty screening and management

Gwyther H, Shaw R, Jaime Dauden E, et al. Understanding frailty: a qualitative study of European healthcare policy-makers' approaches to frailty screening and management. BMJ Open 2018;8:e018653. doi: 10.1136/bmjopen-2017-018653.

At the time this research was done, author Maura Marcucci was affiliated with:

Geriatric Unit, IRCCS Ca' Granda Maggiore Policlinico Hospital Foundation, Milan, Italy; Department of Clinical Sciences & Community Health, University of Milan, Milan, Italy

The new list of affiliations should read:

Holly Gwyther,¹ Rachel Shaw,¹ Eva-Amparo Jaime Dauden,² Barbara D'Avanzo,³ Donata Kurpas,⁴ Maria Bujnowska-Fedak,⁴ Tomasz Kujawa,⁴ Maura Marcucci,^5,6 Antonio Cano,² Carol Holland⁷

Aston Research Centre for Healthy Ageing (ARCHA), Psychology, School of Life and Health Sciences, Aston University, Birmingham, UK

Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Valencia, Spain

Laboratory of Quality Assessment of Geriatric Therapies and Services, IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy

Family Medicine Department, Wroclaw Medical...

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Incidence of delirium in the Canadian emergency department and its consequences on hospital length of stay: a prospective observational multicentre cohort study

Objective

We aim to determine the incidence of delirium and describe its impacts on hospital length of stay (LOS) among non-delirious community-dwelling older adults with an 8-hour exposure to the emergency department (ED) environment.

Design

This is a prospective observational multicentre cohort study (March–July 2015). Patients were assessed two times per day during their entire ED stay and up to 24 hours on hospital ward.

Setting

The study took place in four Canadian EDs.

Participants

338 included patients: (1) aged ≥65 years; (2) who had an ED stay ≥8 hours; (3) were admitted to hospital ward and (4) were independent/semi-independent.

Main outcome(s) and measure(s)

The primary outcomes of this study were incident delirium in the ED or within 24 hours of ward admission and ED and hospital LOS. Functional and cognitive status were assessed using validated Older Americans Resources and Services and the modified Telephone Interview for Cognitive Status tools. The Confusion Assessment Method was used to detect incident delirium. Univariate and multivariate analyses were conducted to evaluate outcomes.

Results

Mean age was 76.8 (±8.1), 17.7% were aged >85 years old and 48.8% were men. The mean incidence of delirium was 12.1% (n=41). Median IQR ED LOS was 32.4 (24.5–47.9) hours and hospital LOS was 146.6 (75.2–267.8) hours. Adjusted mean hospital LOS was increased by 105.4 hours (4.4 days) (95% CI 25.1 to 162.0, P<0.001) for patients who developed an episode of delirium compared with non-delirious patient.

Conclusions

An incident delirium was observed in one of eight independent/semi-independent older adults after an 8-hour ED exposure. An episode of delirium increases hospital LOS by 4 days and therefore has important implications for patients and could contribute to ED overcrowding through a deleterious feedback loop.

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Fluorescence tumor imaging by i.v. administered indocyanine green in a mouse model of colitis-associated colon cancer

Summary

Fluorescence tumor imaging using exogenous fluorescent tumor-targeting agents has potential to improve early tumor detection. The fluorescent contrast agent indocyanine green (ICG) is used in medical diagnostics. The aim of the present study is to investigate the tumor imaging capability and the imaging mechanism of i.v. administered ICG in a mouse model of colitis-associated colon cancer. To do this, an azoxymethane/dextran sodium sulfate-induced colon cancer mouse model was used. Ex vivo imaging experiments were performed 1 hour after i.v. injection of ICG. ICG fluorescence was observed in the colon tumor tissues, with sufficient tumor to normal tissue ratio, correlating with tumor malignancy. In the tumor tissues, ICG fluorescence was localized in the vascular interstitial tissue. Immunofluorescence microscopy revealed that tumor cells formed tight junctions normally, suggesting an inability of tumor cellular uptake of ICG. In contrast, tumor tissues increased the CD31-immunoreactive endothelial cell area, and accumulated stromal cells immunoreactive for cyclooxygenase-2 (COX-2) and tumor cell population immunoreactive for inducible nitric oxide synthase (iNOS). vivo vascular permeability assay revealed that prostaglandin E₂ promoted the endothelial cell permeability of ICG. In conclusion, our data demonstrated that fluorescence contrast-enhanced imaging following i.v. administered ICG can be applied to the detection of colon tumors in a mouse colitis-associated colon cancer model. The tumor tissue preference of ICG in the present model can be attributed to the enhanced vascular leakage of ICG involving inflammatory mediators, such as COX-2 and iNOS, in conjunction with increased tumor vascularity.

This article is protected by copyright. All rights reserved.

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CD169-positive sinus macrophages in the lymph nodes determine bladder cancer prognosis

Summary

CD169⁺ macrophages are suggested to play a pivotal role in establishing anti-tumor immunity. They capture dead tumor cell-associated antigens and transfer their information to lymphocytes including CD8⁺ T cells, which is important for successful tumor suppression. This study aimed to determine the prognostic significance of CD169⁺ macrophages residing in the tumor-draining lymph nodes from cases of bladder cancer. In this retrospective study, 44 bladder cancer patients who received radical cystectomy were examined. The abundance of CD169⁺ macrophages in the regional lymph nodes and the number of CD8⁺ T cells in the primary tumor were investigated by immunohistochemistry. A CD169 score was calculated based on the intensity of CD169 staining and the proportion of CD169⁺ macrophages, and the scores were compared to the patients' clinicopathological parameters. A high CD169 score was significantly associated with low T stage and with a high number of CD8⁺ T cells infiltrating into the tumor. The group with high CD169 expression had significantly longer cancer-specific survival than the group with low CD169 expression (5-year cancer-specific survival rate: 83.3% versus 31.3%). In a multivariate analysis, the CD169 score was identified as the strongest and independent favorable prognostic factor for cancer-specific survival. Our findings suggest that CD169⁺ macrophages in the lymph nodes enhance anti-tumor immunity by expanding CD8⁺ T cells in bladder cancer. The CD169 score may serve as a novel marker for the evaluation of bladder cancer prognosis.

This article is protected by copyright. All rights reserved.

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A novel method for DNA methylation analysis using high-performance liquid chromatography and its clinical application

Summary

The aim of this study was to develop a new methodology that is suitable for DNA methylation diagnostics and to demonstrate its clinical applicability. We developed a new anion-exchange column for high-performance liquid chromatography (HPLC) with electrostatic and hydrophobic properties. Both cytosine and thymine, corresponding to methylated and unmethylated cytosine after bisulfite modification, respectively, are captured by electrostatic interaction and then discriminated from each other by their hydrophobic interactions. The DNA methylation levels of synthetic DNAs were quantified accurately and reproducibly within 10 minutes without time-consuming pretreatment of PCR products, and the measured values were unaffected by the distribution of methylated CpGs within the synthetic DNA fragments. When the DNA methylation status of the FAM150A gene, a marker of the CpG island methylator phenotype specific to clear cell renal cell carcinoma (ccRCC), was examined in 98 patients with ccRCCs, bulk specimens of tumorous tissue including cancer cells showing DNA methylation of the FAM150A gene were easily identifiable by simply viewing the differentiated chromatograms, even when the cancer cell content was low. Sixteen ccRCCs showing DNA methylation more frequently exhibited clinicopathological parameters reflecting tumor aggressiveness, i.e. a larger diameter, higher histological grade, vascular involvement, renal vein tumor thrombi, infiltrating growth, tumor necrosis, renal pelvis invasion and higher pathological Tumor-Node-Metastasis stage, and had significantly lower recurrence-free and overall survival rates. These data indicate that HPLC analysis using this newly developed anion-exchange column can be a powerful tool for DNA methylation diagnostics, including prognostication of patients with cancers, in a clinical setting.

This article is protected by copyright. All rights reserved.

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A computational modeling of blood flow in asymmetrically bifurcating microvessels and its experimental validation

Summary

Microvascular transport is complex due to its heterogeneity. Many researchers have been developing mathematical and computational models in predicting microvascular geometries and blood transport. However, previous works were focused on developing simulation models, not on validating suggested models with microvascular geometry and blood flow in the real microvasculature. In this paper, we suggest a computational model for microvascular transport with experimental validation in its geometry and blood flow. The geometry is generated by controlling asymmetric conditions of microvascular network. Also, the blood flow in microvascular networks is predicted by considering in vivo viscosity, Poiseuille flow model, and hematocrit redistribution by plasma skimming. The suggested model is validated by the measured data in rat mesentery. Also, the microvascular transport in a case of mouse cortex is predicted and compared against experimental data to check applicability of the suggested model. This article is protected by copyright. All rights reserved.

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Surgical versus non-surgical management of type B ankle fractures with minimal talar shift in adults: a systematic review

Background

This systematic review aims to determine the effectiveness of surgical and non-surgical management for the type B ankle fracture with minimal talar shift.

Methods

Two authors independently systematically searched the following databases: MEDLINE, EMBASE and CENTRAL. Only randomized controlled trials were included that evaluated surgical versus non-surgical management of type B ankle fracture with minimal talar shift in adults. Two authors independently performed study selection, risk of bias assessment and data extraction. Main outcomes extracted were general health and ankle function. Heterogeneity was assessed using I² and chi-squared statistic. Data were pooled using fixed effect where appropriate.

Results

Two studies were included involving 241 patients. The pooled mean difference for the physical component score was 0.60 (95% confidence interval (CI): −1.62 to 2.82) non-significantly favouring surgical management. One study reported no significant difference in ankle function (mean difference: 3.20; 95% CI: −6.56 to 12.96) whilst the other reported a significant difference favouring non-surgical management (mean difference: 3.20; 95% CI: 0.44–5.96). Ankle function scores were not pooled due to heterogeneity. Meta-analysis showed that the surgical group was more likely to develop a minor infection (odds ratio: 12.46; 95% CI: 2.29–67.78) or undergo hardware removal (odds ratio: 4.40; 95% CI: 1.09–17.84). There was no significant difference in major infection between the two groups (odds ratio: 4.03; 95% CI: 0.44–36.65; favouring non-surgical management).

Conclusion

There was no significant difference in the general health outcome or ankle function for patients treated surgically versus non-surgically at 12 months. Further follow-up is needed to evaluate longer-term ankle function.

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The role of primary lymph node sites in survival and mortality prediction in Hodgkin lymphoma: a SEER population-based retrospective study

Abstract

As diagnostic and therapeutic modalities for Hodgkin's Lymphoma (HL) continue to improve, patient-related factors affecting survival become more difficult to identify. Very little is known about the relationship between the primary site of lymph node (LN) involvement and survival of HL patients. We retrospectively analyzed the United States Surveillance, Epidemiology and End Results (SEER) database for 12,658 HL patients reported between 1973 and 2010 using survival analysis and time-interval multiple logistic regression (MLR) to disclose that relationship. The effect of all primary LN sites on the survival of HL patients was supported. The intra-abdominal (IAB) primary LN site was significantly associated with the worst survival. The pelvic (P) LN sites were significantly and independently associated with nearly 2 times and 2.5 times the probability of having 1-year overall mortality (OM) and 1-year cancer-specific mortality (CSM), respectively. Head, face and neck (HFN) primary LN sites were significant and independent predictors of better overall and HL-specific survival. A worse survival with the intra-abdominal primary LN site was probably related to their association with higher age, or advanced stages of HL. The biological basis behind the aggressiveness of intra-abdominal and pelvic LN sites is yet to be investigated.

Little is known about the role of primary lymph node sites in survival in Hodgkin lymphoma (HL). This study uses a huge population-based cohort using the SEER database. It was found that intra-abdominal LN sites predict the worst survival in HL patients and that pelvic LN sites were the most aggressive in predicting HL-specific 1-year mortality, and hence, we recommend that primary LN sites be added to future international prognostic scores for HL.

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45th Annual Meeting of the Arbeitsgemeinschaft Dermatologische Forschung (ADF) Zurich, Switzerland, March 7-10, 2018

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Clinical Snippets

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Beyond the physico-chemical barrier: Glycerol and xylitol markedly yet differentially alter gene expression profiles and modify signalling pathways in human epidermal keratinocytes

Abstract

Polyols (e.g. glycerol, xylitol) are implicated as moisturizers of the skin and other epithelial tissues. However, we lack information about their exact cellular mechanisms and their effects on the gene expression profiles. Therefore, in this study, we aimed at investigating the effects of glycerol and xylitol on human epidermal keratinocytes. The polyols (identical osmolarities; xylitol: 0.0045%-0.45%; glycerol: 0.0027%-0.27%) did not alter cellular viability or intracellular calcium concentration. However, they exerted differential effects on the expression of certain genes and signalling pathways. Indeed, both polyols up-regulated the expression of filaggrin, loricrin, involucrin and occludin; yet, xylitol exerted somewhat more profound effects. Moreover, while both polyols stimulated the MAPK pathway, only xylitol induced the activation-dependent translocation of protein kinase Cδ, a key promoter of epidermal differentiation. Finally, in various keratinocyte inflammation models, both polyols (albeit with different efficacies) exerted anti-inflammatory effects. Taken together, these data strongly suggest that glycerol and xylitol differentially modulate expressions of multiple genes and activities of signalling pathways in epidermal keratinocytes. Thus, our findings invite clinical trials to explore the applicability and the impact of a combined glycerol-xylitol therapy in the management of various skin conditions.

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Issue Information

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Relative pelvic version (RPV): an individualized pelvic incidence-based proportional parameter that quantifies pelvic version more precisely than pelvic tilt

Publication date: Available online 8 March 2018
Source:The Spine Journal
Author(s): Caglar Yilgor, Yasemin Yavuz, Nuray Sogunmez, Sleiman Haddad, Anne F. Mannion, Kadir Abul, Louis Boissiere, Ibrahim Obeid, Frank Kleinstück, Francisco Javier Sánchez Pérez-Grueso, Emre Acaroglu, Ferran Pellise, Ahmet Alanay
Background ContextPelvic Tilt (PT) is used as an indicator of pelvic version with increased values indicating retroversion and disability. The concept of using PT solely as an absolute numerical value can be misleading, especially for the patients with Pelvic Incidence (PI) values near the upper and lower normal limits. Relative Pelvic Version (RPV) is a PI-based individualized measure of the pelvic version. RPV indicates the individualized spatial orientation of the pelvis relative to the ideal sacral slope as defined by the magnitude of PI.PurposeThe aim of this study was to compare RPV and PT for their ability to predict mechanical complications and their correlations with HRQoL scores.Study DesignRetrospective analysis of a prospectively collected data of adult spinal deformity patients. Mechanical complications (PJK/PJF, DJK/DJF, rod breakage and implant-related complications) and HRQoL scores (ODI, COMI, SF-36 PCS and SRS-22) were used as outcome measures.MethodsInclusion criteria were ≥4 levels fusion, and ≥2y follow/up. Correlations between PT, RPV, PI and HRQoL were analyzed using Pearson Correlation Coefficient. PI values and mechanical complication rates in RPV subgroups for each PT category were compared using one-way ANOVA, Student's t- and Chi-squared tests. Predictive models for mechanical complications with RPV and PT were analyzed using binomial logistic regressions.Results222 patients (168F, 54M) met the inclusion criteria. Mean age was 52.2±19.3 (18-84) years. Mean follow/up was 28.8±8.2 (24-62) months. There was a significant correlation between PT and PI (r=0.613, p<0.001) threatening the use of PT to quantify pelvic version for different PI values. RPV was not correlated with PI (r=-0.108, p>0.05), being able to quantify pelvic version for all PI values. Compared with PT, RPV had stronger partial correlations with ODI, COMI, SF-36 PCS and SRS-22 scores (p<0.05). Discrimination performance assessed by area under the curve, Percentage Accuracy in Classification, True Positive Rate, True Negative Rate, and Positive and Negative Predictive Values was better for the model with RPV than for PT. For average PI sizes, the agreement between RPV and PT were moderate (=0.609, p<0.001); while the agreement in small and large PI sizes were poor (=0.189, p>0.05; =-0.098, p>0.496, respectively). When analyzed by RPV, each PT '0', '+' and '++' category was further divided into 2 or 3 distinct subgroups of patients having different PI values (p=0.000, p=0.000 and p=0.029, respectively). RPV subgroups within the same PT category displayed different mechanical complication rates (p=0.000, p=0.020 and p=0.019, respectively).ConclusionsPT may be insufficient or misleading in quantifying normoversion for the whole spectrum of PI values when used as an absolute numeric value in conjunction with previously reported population-based average thresholds of 20 and 30 degrees. RPV offers an individualized quantification of ante-, normo- and retroversion for all PI sizes. Schwab PT groups were found to constitute inhomogeneous subgroup of patients with different mean PI values and mechanical complication rates. Compared with PT, RPV showed a greater association with both mechanical complications and HRQoL.



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The effect of inter-body fusion cage design on the stability of the instrumented spine in response to cyclic loading: an experimental study.

Publication date: Available online 8 March 2018
Source:The Spine Journal
Author(s): Ron N. Alkalay, Robert Adamson, Michael W. Groff
Background Context.In the lumbar spine, end plate preparation for the interbody fusion cages may critically affect the cage's long term performance. This study investigated the effect of the interbody cage design on the compliance and cage subsidence of instrumented spines under cyclic compression.Purpose.To quantify the role of cage geometry and bone density on the stability of the spinal construct in response to cyclic compressive loads.Study DesignChanges in the cage-bone interface and the effect of bone density on these changes were evaluated in a human cadaveric model for three intervertebral cage designs.Methods.The intervertebral space of twenty-seven functional cadaveric spinal units was instrumented with: bilateral linear cages, single anterior conformal cages, or single unilateral oblique cages. Once augmented with a pedicle screw fixation system, the instrumented spine unit was tested under cyclic compression loads (400-1200N) to 20,000 cycles at a rate of 2Hz. Compliance of the cage-bone interface and cage subsidence was computed. Two-way Repeated MANOVA was used to test the effects of cage design and bone density on the compliance and subsidence of the cages. The study was funded by a grant from DePuy Synthes ($60,521).Results.The anterior conformal shaped cage showed reduced interface stiffness (p<0.01) and higher hysteresis (p<0.01) and subsidence rate (10-30) %, than the bilateral linear and unilateral oblique shaped cages. Bone density was not associated with the initial compliance of the cage-bone interface or the rate of cage subsidence. Higher bone density did decrease the rate of reduction in cage-bone interface stiffness under higher cyclic loads for the anterior conformal shaped and unilateral oblique cages.Conclusions.Cage design and position significantly affected the degradation of the cage-bone interface under cyclic loading. Comparisons of subsidence rate between the different cage designs suggest the peripheral location of the cages, utilizing the stronger peripheral subchondral bone of the apophasial ring, to be advantageous in preventing the subsidence and failure of the cage-bone interface.



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Effect of posterior instrumented fusion on three-dimensional volumetric growth of cervical ossification of the posterior longitudinal ligament: a multiple regression analysis

Publication date: Available online 8 March 2018
Source:The Spine Journal
Author(s): Jong Joo Lee, Dong Ah Shin, Seong Yi, Keung Nyun Kim, Do Heum Yoon, Hyun Chul Shin, Yoon Ha
Background Context: Despite the fact that ossification of posterior longitudinal ligament (OPLL) is a three-dimensional disease, conventional studies have mainly focused on a two-dimensional measurement, and it is difficult to accurately determine the volume of OPLL growth and analyze the factors affecting OPLL growth after posterior decompression (laminoplasty or laminectomy and fusion).Purpose: This study aimed to investigate the factors affecting OPLL volume growth using a three-dimensional measurement.Study Design/Setting: This was a retrospective case study.Patient Sample: Eighty-three patients with cervical OPLL who were diagnosed as having multilevel cervical OPLL of more than three levels on cervical computed tomography (CT) scans were retrospectively reviewed from June 1, 1998 to December 31, 2015.Outcome Measures: The OPLL volume from the C1 vertebrae to the C7 vertebrae was measured on preoperative and the most recent follow-up CT scans.Methods: Eighty-three patients were retrospectively examined for age, sex, body mass index, hypertension, diabetes, type of OPLL, surgical method, preoperative cervical curvature, and preoperative and postoperative cervical range of motion. Preoperative cervical CT and the most recent follow-up cervical CT scans were converted to digital imaging and communications in medicine data, and the OPLL volume was three-dimensionally measured using the Mimics® program (Materialise, Leuven, Belgium). The OPLL volume growth was analyzed using univariate and multivariate analyses.Results: The average follow-up period was 32.36 (±23.39) months. Patients' mean age was 54.92 (±8.21) years. In univariate analysis, younger age (p = 0.037) and laminoplasty (p = 0.012) were significantly associated with a higher mean annual growth rate of OPLL (%/year). In multivariate analysis, only laminoplasty (p = 0.027) was significantly associated with a higher mean annual growth rate of OPLL (%/year). The mean annual growth rate of OPLL was about 7 times faster with laminoplasty (8.00 ± 13.06%/year) than with laminectomy and fusion (1.16 ± 9.23%/year).Conclusions: Posterior instrumented fusion has the effect of reducing OPLL growth rate rather than motion-preserving laminoplasty. Patients' age and the surgical method need to be considered in surgically managing the multilevel OPLL.



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Contrast gain control and retinogeniculate communication

Abstract

Visual information processed in the retina is transmitted to primary visual cortex via relay cells in the lateral geniculate nucleus (LGN) of the dorsal thalamus. Although retinal ganglion cells are the primary source of driving input to LGN neurons, not all retinal spikes are transmitted to the cortex. Here, we investigate the relationship between stimulus contrast and retinogeniculate communication and test the hypothesis that both the time course and strength of retinogeniculate interactions are dynamic and dependent on stimulus contrast. By simultaneously recording the spiking activity of synaptically connected retinal ganglion cells and LGN neurons in the cat, we show that the temporal window for retinogeniculate integration and the effectiveness of individual retinal spikes are inversely proportional to stimulus contrast. This finding provides a mechanistic understanding for the phenomenon of augmented contrast gain control in the LGN—a non-linear receptive field property of LGN neurons whereby response gain during low-contrast stimulation is enhanced relative to response gain during high-contrast stimulation. In addition, these results support the view that network interactions beyond the retina play an essential role in transforming visual signals en route from retina to cortex.

This article is protected by copyright. All rights reserved.

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Synchronisation in the prefrontal-striatal circuit tracks behavioural choice in a go no-go task in rats

Abstract

Rodent striatum is involved in sensory-motor transformations and reward-related learning. Lesion studies suggest dorsolateral striatum, dorsomedial striatum, and nucleus accumbens underlie stimulus-response transformations, goal-directed behaviour and reward expectation respectively. In addition, prefrontal inputs likely control these functions. Here we set out to study how reward-driven behaviour is mediated by the coordinated activity of these structures in the intact brain. We implemented a discrimination task requiring rats to either respond or suppress responding on a lever after the presentation of auditory cues in order to obtain rewards. Single unit activity in the striatal subregions and prelimbic cortex was recorded using tetrode arrays. Striatal units showed strong onset responses to auditory cues paired with an opportunity to obtain reward. Cue onset responses in both striatum and cortex were significantly modulated by previous errors suggesting a role of these structures in maintaining appropriate motivation or action selection during ongoing behaviour. Furthermore, failure to respond to the reward-paired tones was associated with higher pre-trial coherence among striatal subregions and between cortex and striatum suggesting a task-negative corticostriatal network whose activity may be suppressed to enable processing of reward-predictive cues. Our findings highlight that coordinated activity in a distributed network including both prelimbic cortex and multiple striatal regions underlies reward-related decisions.

This article is protected by copyright. All rights reserved.

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My Prolonged Collaboration with Ray Guillery

Abstract

My active collaboration with Ray Guillery started in 1968, when he was a Full Professor at the University of Wisconsin and I was a graduate student at the University of Pennsylvania. The collaboration lasted almost 50 years with virtually no breaks. Among the ideas we proposed are that glutamatergic pathways in thalamus and cortex can be classified into drivers and modulators; that many thalamic nuclei could be classified as higher order, meaning that they receive driving input from layer 5 of cortex and participate in cortico-thalamo-cortical circuits; and that much of the information relayed by thalamus serves as an efference copy for motor commands initiated by cortex.

This article is protected by copyright. All rights reserved.

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Frequency-dependent Anisotropic Modelling and Analysis Using mfEIT: A Computer Simulation Study

Abstract

Electrical properties of human tissues are usually linked with structure of thin insulating membranes and thereby reflect physiological function of the tissues or organs. It is clinically important to characterize electrical properties of tissues in vivo. Electrical impedance tomography (EIT) is a recently developed medical imaging technique which has been exploited to characterize electrical properties (conductivity and permittivity) of human tissues by injecting currents and measuring the resulting voltages at boundary electrodes. The electrical characteristic of a majority of human tissues, such as bones, muscles and brain white matter etc, exhibits an anisotropic property. The anisotropic phenomenon of human tissues is frequency dependent that vanishes at high frequencies. Previous EIT studies which aimed at the reconstruction of anisotropic subject tissues have been focused on the theoretical analysis of uniqueness up to a diffeomorphism or the establishment of an accurate forward model by using an anisotropic conductivity tensor. However, effects of the current frequency on the accuracy of the reconstructions of anisotropic subjects remain poorly studied. The goal of this study is to examine the feasibility of multi-frequency electrical impedance tomography (mfEIT) by employing it in a simulation study to recover the frequency-dependent anisotropic properties of a phantom subject comprised of alternating insulating-and-conductive layers. The anisotropic properties of the subject were analysed by an effective admittivity tensor, and the responses of the current flow pathways and voltages were investigated at various applied current frequencies in the forward model. The linear reconstruction was performed following the sensitivity matrix approach at multiple frequencies. Simulation results achieved at various frequencies revealed that the anisotropy of the model was effectively reconstructed at low frequencies and disappeared at high frequencies, from which we validated the feasibility of mfEIT method in reconstructing the anisotropic directions of the considered object.

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Improved Genome Assembly and Annotation for the Rock Pigeon (Columba livia)

The domestic rock pigeon (Columba livia) is among the most widely distributed and phenotypically diverse avian species. C. livia is broadly studied in ecology, genetics, physiology, behavior, and evolutionary biology, and has recently emerged as a model for understanding the molecular basis of anatomical diversity, the magnetic sense, and other key aspects of avian biology. Here we report an update to the C. livia genome reference assembly and gene annotation dataset. Greatly increased scaffold lengths in the updated reference assembly, along with an updated annotation set, provide improved tools for evolutionary and functional genetic studies of the pigeon, and for comparative avian genomics in general.

http://ift.tt/2tt0ruC

Inducible Genome Editing with Conditional CRISPR/Cas9 Mice

Genetically engineered mouse models (GEMMs) are powerful tools by which to probe gene function in vivo, obtain insight into disease etiology, and identify modifiers of drug response. Increased sophistication of GEMMs has led to the design of tissue-specific and inducible models in which genes of interest are expressed or ablated in defined tissues or cellular subtypes. Here we describe the generation of a transgenic mouse harboring a doxycycline-regulated Cas9 allele for inducible genome engineering. This model provides a flexible platform for genome engineering since editing is achieved by exogenous delivery of sgRNAs and should allow for the modelling of a range of biological and pathological processes.

http://ift.tt/2FmjfBf

Functional Validation of Candidate Genes Detected by Genomic Feature Models

Understanding the genetic underpinnings of complex traits requires knowledge of the genetic variants that contribute to phenotypic variability. Reliable statistical approaches are needed to obtain such knowledge. In genome-wide association studies, variants are tested for association with trait variability to pinpoint loci that contribute to the quantitative trait. Because stringent genome-wide significance thresholds are applied to control the false positive rate, many true causal variants can remain undetected. To ameliorate this problem, many alternative approaches have been developed, such as genomic feature models (GFM). The GFM approach tests for association of set of genomic markers, and predicts genomic values from genomic data utilizing prior biological knowledge. We investigated to what degree the findings from GFM have biological relevance. We used the Drosophila Genetic Reference Panel to investigate locomotor activity, and applied genomic feature prediction models to identify gene ontology (GO) categories predictive of this phenotype. Next, we applied the covariance association test to partition the genomic variance of the predictive GO terms to the genes within these terms. We then functionally assessed whether the identified candidate genes affected locomotor activity by reducing gene expression using RNA interference. In five of the seven candidate genes tested, reduced gene expression altered the phenotype. The ranking of genes within the predictive GO term was highly correlated with the magnitude of the phenotypic consequence of gene knockdown. This study provides evidence for five new candidate genes for locomotor activity, and provides support for the reliability of the GFM approach.

http://ift.tt/2oW69Ay

Rapid Nuclear Exclusion of Hcm1 in Aging Saccharomyces cerevisiae Leads to Vacuolar Alkalization and Replicative Senescence

The yeast, Saccharomyces cerevisiae, like other higher eukaryotes, undergo a finite number of cell divisions before exiting the cell cycle due to the effects of aging. Here, we show that yeast aging begins with the nuclear exclusion of Hcm1 in young cells, resulting in loss of acidic vacuoles. Autophagy is required for healthy aging in yeast, with proteins targeted for turnover by autophagy directed to the vacuole. Consistent with this, vacuolar acidity is necessary for vacuolar function and yeast longevity. Using yeast genetics and immunofluorescence microscopy, we confirm that vacuolar acidity plays a critical role in cell health and lifespan, and is potentially maintained by a series of Forkhead Box (Fox) transcription factors. An interconnected transcriptional network involving the Fox proteins (Fkh1, Fkh2 and Hcm1) are required for transcription of v-ATPase subunits and vacuolar acidity. As cells age, Hcm1 is rapidly excluded from the nucleus in young cells, blocking the expression of Hcm1 targets (Fkh1 and Fkh2), leading to loss of v-ATPase gene expression, reduced vacuolar acidification, increased α-syn-GFP vacuolar accumulation, and finally, diminished replicative lifespan (RLS). Loss of vacuolar acidity occurs about the same time as Hcm1 nuclear exclusion and is conserved; we have recently demonstrated that lysosomal alkalization similarly contributes to aging in C. elegans following a transition from progeny producing to post-reproductive life. Our data points to a molecular mechanism regulating vacuolar acidity that signals the end of RLS when acidification is lost.

http://ift.tt/2HfDpta

Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project

Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project

Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project, Published online: 09 March 2018; doi:10.1038/s41416-018-0007-z

Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project

http://ift.tt/2oYgISM

Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank

Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank

Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank, Published online: 08 March 2018; doi:10.1038/bjc.2017.496

Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank

http://ift.tt/2oUJswB

Artificial limb representation in amputees

Abstract

The human brain contains multiple hand-selective areas, in both the sensorimotor and visual systems. Could our brain repurpose neural resources, originally developed for supporting hand function, to represent and control artificial limbs? We studied individuals with congenital or acquired hand-loss (hereafter one-handers) using functional MRI. We show that the more one-handers use an artificial limb (prosthesis) in their everyday life, the stronger visual hand-selective areas in the lateral occipitotemporal cortex respond to prosthesis images. This was found even when one-handers were presented with images of active prostheses that share the functionality of the hand but not necessarily its visual features (e.g. a 'hook' prosthesis). Further, we show that daily prosthesis usage determines large-scale inter-network communication across hand-selective areas. This was demonstrated by increased resting state functional connectivity between visual and sensorimotor hand-selective areas, proportional to the intensiveness of everyday prosthesis usage. Further analysis revealed a 3-fold coupling between prosthesis activity, visuomotor connectivity and usage, suggesting a possible role for the motor system in shaping use-dependent representation in visual hand-selective areas, and/or vice versa. Moreover, able-bodied control participants who routinely observe prosthesis usage (albeit less intensively than the prosthesis users) showed significantly weaker associations between degree of prosthesis observation and visual cortex activity or connectivity. Together, our findings suggest that altered daily motor behaviour facilitates prosthesis-related visual processing and shapes communication across hand-selective areas. This neurophysiological substrate for prosthesis embodiment may inspire rehabilitation approaches to improve usage of existing substitutionary devices and aid implementation of future assistive and augmentative technologies.

http://ift.tt/2tsRzoO

A phase I trial of escalating doses of cixutumumab (IMC-A12) and sorafenib in the treatment of advanced hepatocellular carcinoma

Abstract

Purpose

The insulin-like growth factor (IGF) pathway is activated in hepatocarcinogenesis. Cixutumumab is a monoclonal antibody against human insulin-like growth factor-1 receptor (IGF-1R). Given the cross-talk between the IGF and VEGF pathways, we performed a phase I study of the combination of cixutumumab and sorafenib in hepatocellular cancer (HCC).

Methods

Eligible patients with no prior systemic therapy for advanced HCC and Child–Pugh A to B7 were treated with sorafenib 400 mg BID and escalating doses of cixutumumab (2, 4, or 6 mg/kg IV weekly) in a 3 + 3 design. Dose limiting toxicity (DLT) was defined as treatment-related grade 3 or 4 non-hematologic toxicity (except for a subset of manageable toxicities) or any grade 4 hematologic toxicities.

Results

In 21 patients enrolled, there were 3 DLTs; grade 3 hyperglycemia, grade 3 hypophosphatemia, and grade 5 peritonitis. The maximum tolerated dose of cixutumumab was 4 mg/kg IV weekly with standard dose sorafenib. Eighteen of 21 (86%) patients had grade 3 or above toxicities attributed to treatment. One patient also experienced grade 4 colonic perforation and grade 5 peritonitis. The median number of cycles completed was 4 (0–26). Of 16 patients evaluable for response, 81% achieved stable disease. The median progression free survival was 6.0 months (95% CI 3.6–undefined) and the median overall survival was 10.5 months (95% CI 7.1–undefined).

Conclusions

While the combination of cixutumumab and sorafenib had a toxicity profile similar to that of sorafenib monotherapy, it manifested limited clinical efficacy in unselected patients with HCC.

http://ift.tt/2p0C8ic

Liquid Biopsy in Primary Brain Tumors: Looking for Stardust!

Abstract

Purpose of Review

Personalized medicine is a challenge to improve survival and quality of life of patients suffering from primary malignant brain tumor. Molecular biology is integrated in initial diagnosis and relapse, and, in the nearest future, over treatment schedule and monitoring. Liquid biopsy is a minimally invasive way to obtain tumor material.

Recent Findings

Over the past years, three fluids have been explored to provide tumor information in primary malignant brain tumor: blood, cerebrospinal fluid, and vitreous liquid. Different tumor components were identified: (1) circulating tumor cells, (2) circulating tumor DNA, (3) RNA and non-coding miRNA, and (4) extracellular vesicles. The performance of the liquid biopsy depends on the tumor type and on the method of detection.

Summary

Liquid biopsy could be a valuable tool to improve patient care in primary malignant brain tumor. Improvement of its sensitivity is the major challenge to generalize its use in daily practice.

http://ift.tt/2ttagc7

Personalized Pain Goal as an Outcome Measure in Routine Cancer Pain Assessment

Personalized pain goal is a feasible pain outcome measure in routine cancer pain management. Higher baseline pain intensity, depression, opioid dose, and number of adjuvant analgesics were predictors of poor pain relief.

http://ift.tt/2Fro6NF

A palliative radiation oncology consult service reduces total costs during hospitalization

Palliative radiation therapy (PRT) is a highly effective treatment in alleviating symptoms from bone metastases; however, currently used standard fractionation schedules can lead to costly care, especially when patients are treated in an inpatient setting. The Palliative Radiation Oncology Consult (PROC) service was developed in 2013 to improve appropriateness, timeliness, and care value from PRT.

http://ift.tt/2G8yB9E

Psychiatric comorbidity, health related quality of life, and mental health service utilization among patients awaiting liver transplant

The prevalence of psychiatric disorders and mental health service utilization among patients with End Stage Liver Disease (ESLD) awaiting transplant remains understudied.

http://ift.tt/2Fr55Lg

Prediction of secondary generalization from a focal onset seizure in intracerebral EEG

Approximately 30% of patients with focal epilepsy are unresponsive to antiepileptic medications and many are considered surgical candidates (Johnson and Krauss, 2016). These patients continue to experience several physical and physiological complications and the conditions become worse when their uncontrolled seizures evolve from focal to bilateral tonic-clonic seizure (van Mierlo et al., 2014). Such seizures severely affect the patient's safety and quality of life (Yang et al., 2017; Yoo et al., 2014).

http://ift.tt/2FCWVTy

An evaluation of kurtosis beamforming in magnetoencephalography to localize the epileptogenic zone in drug resistant epilepsy patients

The aim of epilepsy surgery is to remove the epileptogenic zone (EZ), i.e. the region whose removal ensures postoperative seizure freedom (Engel, 1996; Lüders et al., 2006). Hypotheses about the location of the EZ are typically generated on the basis of the patient's clinical history, as well as electroencephalography (EEG), neuropsychological and neuroimaging assessments (Engel, 1996; Lüders et al., 2006; Dorfer et al., 2015). Approximately 15-25% of patients yield inconclusive or non-localizing results (Zumsteg et al., 2000; Carrette et al., 2010) often meaning that additional invasive testing is required (Blount et al., 2008).

http://ift.tt/2FCDiLe

A reappraisal of the mechanisms of action of ketamine to treat complex regional pain syndrome in the light of cortical excitability changes

Complex regional pain syndrome (CRPS) is a multi-symptom, multi-system painful syndrome whose pathophysiological mechanisms remain partly unknown. The acronym CRPS refers to a disorder characterized by spontaneous or stimulus-induced pain that is disproportionate to the inciting event and is accompanied by a combination of various autonomic and motor disturbances. The activation of the sympathetic nervous system is likely involved. A neurological injury, when identified, is generally peripheral, leading to the distinction between CRPS type I (without nerve injury) and type II (with nerve injury).

http://ift.tt/2p0y8yq

Event-related brain potentials elicited by high-speed cooling of the skin: a robust and non-painful method to assess the spinothalamic system in humans

Neuropathic pain is defined by the International Association for the Study of Pain as "pain arising as a direct consequence of a lesion or disease of the somatosensory system" (Loeser and Treede, 2008). This implies that the diagnostic work-up of neuropathic pain requires clinical tools to assess the function of the somatosensory system, including the function of the spinothalamic system. The most recent guidelines on neuropathic pain assessment state that the recording of laser-evoked brain potentials (LEPs) – i.e.

http://ift.tt/2p17Qfv

The effect of neoadjuvant androgen deprivation therapy on tumour hypoxia in high-grade prostate cancer: a 18F-MISO PET/MRI imaging study.

Tumour hypoxia is associated to treatment resistance. In this prospective study of 11 patients, we evaluated the occurrence of hypoxia in high-grade prostate cancer by multiparametric integrated18F-MISO PET/MRI before and after 3 months of androgen deprivation. Our results show the presence of hypoxic conditions in prostate carcinoma, correlated with tumour grade and responding to androgen ablation, thus supporting the re-oxygenation role of a neoadjuvant androgen deprivation therapy phase in combination with curative radiotherapy.

http://ift.tt/2oUGPed

Systematic review and meta-analysis in gastrointestinal endoscopy: Why do we need them? How can we read them? Should we trust them?

http://ift.tt/2FlOdd4

Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank

http://ift.tt/2IaeiJI

Analysis of Cell-free DNA to Assess Risk of Tumoremia Following Endoscopic Ultrasound Fine-needle Aspiration of Pancreatic Adenocarcinomas

Cellular and nuclear material from tumors disseminates into the bloodstream (tumoremia), but it is not clear whether medical procedures cause release of this material or contribute to formation of metastases. We performed a prospective study of blood samples from patients with pancreatic adenocarcinoma (PDAC) to determine whether endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) associates with markers of tumoremia.

http://ift.tt/2oUWmdY

Rituximab Maintenance Therapy Reduces Rate of Relapse of Pancreaticobiliary Immunoglobulin G4-related Disease

Rituximab maintenance therapy should be considered for patients with relapsing pancreaticobiliary IgG4-RD who receive induction rituximab treatment. Younger age, persistent disease activity after induction therapy, and increased serum concentrations of alkaline phosphatase either before or after induction therapy, associate with increased risk of relapse. These factors should be considered in deciding whether or not to provide maintenance rituximab therapy.

http://ift.tt/2HkNbKR

Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project

http://ift.tt/2IePct6

Mental health and well-being concerns of fly-in fly-out workers and their partners in Australia: a qualitative study

Objectives

Fly-in fly-out (FIFO) work involves commuting long distances to the worksite and living in provided accommodation for 1–4 weeks while on shift. While the potentially detrimental impact of FIFO work on the health and well-being of workers has been documented, little attention has been paid to how workers, or their partners, cope with this impact. This study sought to investigate how workers and their partners negotiate the impact of FIFO on their mental health and well-being.

Design

The study design was qualitative. FIFO workers and partners responded to open-ended questions on concerns about the FIFO lifestyle and the support they use.

Setting

Australian FIFO workers and partners responded to the questions via email.

Participants

Participants were 34 FIFO workers (25 men, M age=41 years) and 26 partners of FIFO workers (26 women, M age=40 years).

Results

Participant-validated thematic analysis generated three main themes: managing multiple roles, impact on mental health and well-being, and social support needs. Results revealed difficulties in adjusting between the responsibilities of perceptually distinct on-shift and off-shift lives, and managing potential psychological distance that develops while workers are on site. Participants emphasised the importance of maintaining quality communication and support from family members. Workers and partners attempted to maintain mental health and well-being by regularly engaging with support networks, although many felt organisational support was tokenistic, stigmatised or lacking.

Conclusions

Recommendations for enhancing support provided by FIFO organisations are offered. In particular, organisations should emphasise the importance of good mental health and well-being, maintain transparency regarding potential challenges of FIFO lifestyles, and offer professional support for managing multiple social roles and effective communication.

http://ift.tt/2G8Erb9

Targeting BCL-2 in Hematologic Malignancies

Abstract

Resistance to apoptosis is one of the hallmarks of cancer and members of the B-cell lymphoma 2 (BCL-2) family of proteins are central regulators of apoptosis. Many cancers become resistant to chemotherapy and apoptosis by up-regulating BCL-2 and other family members, making these proteins attractive targets for cancer therapy. Venetoclax is an orally administered, small-molecule apoptosis stimulant that targets BCL-2 proteins by acting as a BCL-2 homology domain 3 (BH3) mimetic. The drug is approved in the USA and EU as a monotherapy for the for the treatment of certain patients with chronic lymphocytic leukemia (CLL) and is in phase III clinical development for multiple myeloma (MM), and in phase II or I/II clinical trials for acute myeloid leukemia, and several B-cell malignancies, including diffuse large B-cell lymphoma, Waldenstrom's macroglobulinaemia, follicular lymphoma, and mantle-cell lymphoma.

http://ift.tt/2G7KY66

Puncture-Induced Iris Neovascularization as a Mouse Model of Rubeosis Iridis

Iris neovascularization, a common complication of ischemic retinal disease, may lead to sight-threatening neovascular glaucoma. Here, we describe a murine protocol for inducing experimental iris neovascularization that may be used for noninvasive evaluation of angiogenesis-modulating substances.

http://ift.tt/2Ics4eT

Robust DNA Isolation and High-throughput Sequencing Library Construction for Herbarium Specimens

This article demonstrates a detailed protocol for DNA isolation and high-throughput sequencing library construction from herbarium material including rescue of exceptionally poor-quality DNA.

http://ift.tt/2Db8ZpI

Midwives and clinical investigation: A review of the literature

Publication date: Available online 8 March 2018
Source:Women and Birth
Author(s): Catherine R. Alexander, Fiona Bogossian
BackgroundAn allegation of negligence or an adverse outcome during childbirth can lead to clinical investigation of a midwife's practice. Anecdotal evidence suggests midwives find this stressful and disturbing.AimSynthesise the evidence relating to midwives' experiences of investigation and the effects on clinical practice and personal wellbeing.MethodsTwo database searches were conducted between 2015 and 2016 to identify primary research published between 1990 and 2016. Studies were evaluated for quality using standard instruments.FindingsDespite numerous references to 'litigation' in peer-reviewed journals, little substantive research related specifically to midwives. 11 inclusions comprised three qualitative studies (one with two publications), reporting litigation experiences of midwives and seven quantitative studies (four research groups), identifying risk liability through cyclic surveys of midwives and law reports. Failure to identify deterioration in foetal well-being was a common finding among researchers examining reasons for litigation. Experienced midwives were at highest risk of litigation. Researchers found high levels of distress and abreaction among participants who either stopped working in birth suite or left midwifery. They also identified a level of ambiguity around defensive practices associated with fear of litigation.ConclusionThere is little research regarding experiences of midwives and clinical investigation. Midwives under investigation need appropriate support. Continuing to work during prolonged investigative processes is stressful as reported by midwives who described being "ill-equipped" and "unprepared." Midwives in the review preferred the support of colleagues over counsellors. Educators, employers and regulators need to work collaboratively and incorporate reflective practice in targeted support.



http://ift.tt/2IeYK7k

Mobile Game-based Virtual Reality Program for Upper Extremity Stroke Rehabilitation

Here, we present a protocol to develop and apply a mobile game-based virtual reality program for the recovery of upper limb dysfunction in patients with stroke. The present study shows that the mobile program is feasible and effectively promotes upper limb recovery in stroke patients.

http://ift.tt/2oUN1mr

Use of a Psychophysiological Script-driven Imagery Experiment to Study Trauma-related Dissociation in Borderline Personality Disorder

We present a protocol of personalized script-driven trauma-related imagery and clinical assessments within a comparison design for investigating peritraumatic dissociation (PD), psychophysiological reactions, i.e. heart rate (HR) and skin conductance (SC), and psychological features of often severely traumatized individuals with borderline personality disorder (BPD).

http://ift.tt/2tucAzy

Diagnostic Model of Serum miR-193a-5p, HE4 and CA125 Improves the Diagnostic Efficacy of Epithelium Ovarian Cancer

Abstract

Epithelium ovarian cancer (EOC) is currently the prevalent malignant cancer worldwide. However, there is a lack of efficient biomarkers for EOC screening. Accumulating evidence reveals that serum miRNA detectable in various types of cancer. Therefore, we explore the diagnostic value of combined detection of plasma miR-193a-5p, HE4 and CA125 for EOC. Serum samples were collected from 45 patients with primary EOC, 30 patients with benign ovarian tumor patients and 40 healthy controls. The expression of serum miR-193a-5p was detected by real-time quantitative PCR, and serum HE4 and CA125 were detected by chemiluminescent immunoassay. Moreover, a diagnostic model combining miR-193a-5p, HE4 and CA125 or alone in EOC patients was evaluated by ROC curve analysis. The relative expression quantity (RQ) of serum miR-193a-5p in EOC patients, benign ovarian tumor patients and healthy control groups were 0.419 (0.093, 2.215), 3.667 (1.633, 6.691) and 1.130 (1.000, 7.087), respectively. The RQ of serum miR-193a-5p in EOC patients was significantly lower than that in benign ovarian tumor patients and healthy controls (both P < 0.001), and there was no significant difference between benign ovarian tumor patients and healthy controls (both P > 0.05). There was no significant correlation between serum miR-193-5p, HE4 and CA125 levels (both P > 0.05). Additionally a risk model for miR-193a-5p, HE4 and CA125 was correlated with Grading and Lymph node metastasis (P = 0.016, P = 0.029). The area under the receiver operating characteristic curve of a risk model for distinguishing EOC patients from healthy individuals was 0.996, which higher than any single biomarker. Combined detection of miR-193-5p, HE4 and CA125 by logistic regression analysis could greatly improved the diagnostic ability of EOC and may prove to be a candidate biomarker, providing new directions for further investigation.

http://ift.tt/2G7IrJ4