Cells Under Stress: An Inertial-Shear Microfluidic Determination Of Cell Behaviour

The deformability of a cell is the direct result of a complex interplay between the different constituent elements at the subcellular level, coupling a wide range of mechanical responses at different length-scales. Changes to the structure of these components can also alter cell phenotype, thus the critical importance of cell mechano-response for diagnostic applications. The response to mechanical stress depends strongly on the forces experienced by the cell. Here we use cell deformability in both shear-dominant and inertia-dominant microfluidic flow regimes to probe different aspects of the cell structure.

http://bit.ly/2Sfs8mI

Motor dynamics underlying cargo transport by pairs of kinesin-1 and kinesin-3 motors

Intracellular cargo transport by kinesin family motor proteins is crucial for many cellular processes, particularly vesicle transport in axons and dendrites. In a number of cases, transport of specific cargo is carried out by two classes of kinesins that move at different speeds and thus compete during transport. Despite advances in single-molecule characterization and modeling approaches, many questions remain regarding the effect of inter-motor tension on motor attachment/re-attachment rates during cooperative multi-motor transport.

http://bit.ly/2SfGOlZ

Spontaneous spatial correlation of elastic modulus in jammed epithelial monolayers observed by AFM

For isolated single cells on a substrate, the intracellular stiffness, which is often measured as the Young's modulus, E, by atomic force microscopy (AFM), depends on the substrate rigidity. However, little is known about how the E of cells is influenced by the surrounding cells in a cell population system where cells physically and tightly contact adjacent cells. In this study, we investigated the spatial heterogeneities of E in a jammed epithelial monolayer in which cell migration was highly inhibited, allowing us to precisely measure the spatial distribution of E in large-scale regions by AFM.

http://bit.ly/2UHTrD5

Elevated Pretreatment CEA and CA19-9 Levels are Related to Early Treatment Failure in Esophageal Adenocarcinoma

Introduction: Chemoradiotherapy and surgery are the basis of the potentially curative treatment for esophageal cancer. Approximately 1 in 5 patients, however, do not benefit from this intensive treatment due to early treatment failure. The aim of this study was to evaluate levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 at diagnosis, in relation to survival and early treatment failure (disease recurrence or death within 1 year after surgery). Methods: Patients with esophageal adenocarcinoma scheduled for chemoradiotherapy followed by surgery between 1998 and 2014 were selected from a retrospectively collected database if both CEA and CA19-9 levels were measured before the start of treatment. Results: Pretreatment CEA and CA19-9 levels were known in 102 patients. Median overall survival differed (P

http://bit.ly/2REGTdD

Application of a Prognostic Stratification System for High-risk Prostate Cancer to Patients Treated With Radiotherapy: Implications for Treatment Optimization

Objectives: We applied an established prognostic model to high-risk prostate cancer (HRPC) patients treated with radiotherapy (RT) and evaluated the influence of clinical and treatment variables on treatment outcomes. Methods: In total, 1075 HRPC patients undergoing definitive radiotherapy (RT) between 1995 and 2010 were retrospectively reviewed. Median follow-up was 62.3 months. Patients received either dose-escalated external beam radiotherapy (n=628, EBRT) or combined-modality radiotherapy (n=447, pelvic RT and low-dose rate brachytherapy boost, CMRT). 82.9% received androgen-deprivation therapy (ADT). A prognostic model stratified patients into predefined groups (good, intermediate, and poor). Kaplan-Meier methods and Cox proportional hazards regressions assessed biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM) and overall mortality (OM). C-indices analyzed predictive value. Results: The model was prognostic; C-indices for BF, DM, PCSM and OM were: 0.62, 0.64, 0.61, and 0.57. On multivariate analysis, CMRT and longer ADT (≥24 mo) were associated with improved BF, DM, and PCSM. Gleason score (GS) 9-10 was the strongest predictor of PCSM. C-indices for BF, DM, PCSM, and OM using a 4-compartment model incorporating GS 9-10 were: 0.62, 0.65, 0.68, and 0.56. In poor-prognosis patients (GS 8-10+additional risk factors), CMRT+LTADT (>12 mo) had 10-year PCSM (3.7%±3.6%), comparing favorably to 25.8%±9.2% with EBRT+LTADT. Conclusions: The model applies to high-risk RT patients; GS 9-10 remains a powerful predictor of PCSM. Comparing similar prognosis patients, CMRT is associated with improved disease-specific outcomes relative to EBRT. In poor-prognosis patients, CMRT+LTADT yields superior 10-year PCSM, potentially improving RT treatment personalization for those with HRPC. B.F., W.J. and D.H. contributed to statistical analyses and all authors were instrumental in manuscript review and editing. The authors declare no conflicts of interest. Reprints: Daniel Hamstra, MD, PhD, 18101 Oakwood Boulevard, Lower Level, Beaumont Hospital, Department of Radiation Oncology, Dearborn, MI 48124. E-mail: daniel.hamstra@beaumont.org. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2WMASPN

Tobacco Treatment Programs at National Cancer Institute-designated Cancer Centers: A Systematic Review and Online Audit

Objectives: The main objectives of this study were to evaluate abstinence rates of tobacco treatment programs (TTPs) at National Cancer Institute (NCI)-designated cancer centers (DCCs) and to ascertain the number of NCI-DCCs with online references to TTPs. Methods: Literature searches of Pubmed, EMBASE, Web of Science, and Scopus were performed from their inception through January 2018 using keywords including cancer patients, cancer survivors, tobacco, smoking, cessation, and program. In total, 4094 articles were identified, 1450 duplicates were removed, 2644 candidate titles and abstracts were screened, and 210 selected full-text articles were independently reviewed by 2 authors. Three retrospective, single-institution cohort studies describing system-wide TTPs at 3 NCI-DCCs met inclusion criteria. Secondarily, online website audits of each NCI-DCC were performed to identify institutions with online evidence of a system-wide TTP servicing cancer patients. Results: Among 62 NCI-DCCs, only 3 reported system-wide TTP outcomes. Abstinence rates ranged from 15% to 47%. Online website audit identified 47 NCI-DCCs maintaining system-wide TTPs. Seventeen TTPs were housed within the cancer center and 30 TTPs were offered by the primary affiliated institution; among the latter group, only 13 TTPs were identifiable via the NCI-DCC webpage. Conclusions: Most NCI-DCCs offer tobacco treatment services to cancer patients but very few have reported their results. Increased NCI-DCC TTP outcome publication and online presence are needed. The authors declare no conflicts of interest. Reprints: Andrew T. Day, MD, MPH, Department of Otolaryngology - Head and Neck Surgery, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9035. E-mail: andrew.day@utsouthwestern.edu. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2REGSq5

Pattern of Marginal Local Failure in a Phase II Trial of Neoadjuvant Chemotherapy and Stereotactic Body Radiation Therapy for Resectable and Borderline Resectable Pancreas Cancer

Objectives: The main objectives of this study were to prospectively evaluate the safety and efficacy of stereotactic body radiation therapy (SBRT) in the neoadjuvant setting for resectable or borderline resectable pancreatic cancer. Materials and Methods: Eighteen patients were enrolled from November 2014 to June 2017. Following 3 cycles of chemotherapy, SBRT was delivered to the tumor and abutting vessel and a 3 mm planning target volume (PTV) margin to 33 Gy (6.6 Gy×5) with an optional elective PTV to 25 Gy (5 Gy×5) customized to the nodal space and mesenteric vessels. The primary endpoint is ≥grade 3 acute and late gastrointestinal toxicity. Results: Fifteen patients had borderline resectable tumors due to arterial abutment (n=7) or superior mesenteric vein encasement (n=8); 3 patients had resectable tumors. There were no ≥grade 3 acute or late gastrointestinal events. Following SBRT, surgery was performed in 12 patients (67%) with 11 (92%) R0 resections. The median overall survival and progression-free survival was 21 months (95% CI: 18-29) and 11 months (95% CI: 8.4-16). Progression occurred in 83% (10/12) of resected patients (distant [n=4, 40%], local-only [n=4, 40%], and local and distant [n=2, 20%]). The cumulative incidence of local failure (LF) at 12 months from resection was 50% (95% CI: 20-80). All LF were outside to the PTV33. Conclusions: Neoadjuvant SBRT was well tolerated, however LFs were predominantly observed outside the PTV33 volume that would have been covered with conventional RT volumes. The durability of local control after SBRT in the neoadjuvant setting merits examination relative to chemoradiation before incorporation into routine practice. The authors declare no conflicts of interest. Reprints: Jordan Kharofa, MD, Department of Radiation Oncology, University of Cincinnati, 234 Goodman Street, ML 0757, Cincinnati, OH 45267-0757. E-mail: kharofjr@ucmail.uc.edu. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2WIZBVf

Dual Modality Radiation With External Beam Radiation Therapy and Transarterial Radioembolization for Hepatocellular Carcinoma With Gross Vascular Invasion

Objectives: Patients with hepatocellular carcinoma (HCC) and gross vascular invasion (GVI) have poor outcomes with systemic therapy such as sorafenib. Both external beam radiation therapy (EBRT) and transarterial radioembolization (TARE) have been utilized for this patient population. We sought to compare outcomes using dual modality radiation (EBRT+TARE) versus EBRT alone in patients with HCC and GVI. Materials and Methods: Between 2011 and 2017, 45 patients with HCC and GVI were treated with EBRT±TARE at our institution. Progression-free survival (PFS) and overall survival (OS) were assessed and compared using Kaplan-Meier method and log-rank test. Univariable and multivariable Cox proportional hazards regression was used to assess the impact of the variables stage, etiology of cirrhosis, Child-Pugh (CP) score, and Karnofsky Performance Score (KPS) on PFS and OS. Results: Patient characteristics were well-balanced except for KPS (80 vs. 90) and CP score. Median OS for patients receiving EBRT+TARE was 263 days (95% confidence interval [CI]: 167, -) versus 193 days (95% CI: 51, 262) for EBRT alone (P=0.049). However, this did not hold up on MVA. When EBRT and TARE were delivered within 2 months as planned (n=12), median PFS was 218 days (95% CI: 44, -) for dual modality radiation versus 63 days (95% CI: 38, 137) for EBRT alone (P=0.048). When EBRT and TARE were delivered within 6 months, the difference in PFS was no longer seen (P=NS), because some patients received TARE as a salvage therapy. Conclusions: Dual modality radiation with EBRT and TARE may be associated with improved OS in patients with HCC and GVI. Dual modality radiation may be associated with improved PFS in patients with HCC and GVI compared with EBRT alone when EBRT and TARE are delivered within 2 months of each other as part of a planned dual modality treatment strategy. However, since this is a retrospective study with inherent selection bias, these findings need further validation in a prospective clinical trial for patients with HCC and GVI. Supported by Biostatistics Shared Resource Facility, Icahn School of Medicine at Mount Sinai and NCI Cancer Center Support Grant P30 CA196521-01. H.M. serves on an advisory board for AstraZeneca. E.K. serves on an advisory board for BTG plc. A.F. serves as a consultant for Terumo and on an advisory board for Embolx Inc. The remaining authors declare no conflicts of interest. Reprints: Michael Buckstein, MD, PhD, Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029. E-mail: Michael.buckstein@mountsinai.org. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2RJLv2p

Contrasting the Clinical Presentation and Prevalence of Septic, Reactive, and Crystal Arthritis in Patients With Hematologic and Solid Malignancies

Background The development of septic arthritis requires rapid identification and treatment to prevent serious and irreversible complications in cancer patients. This is further emphasized by the fact that many cancer patients are immunocompromised either through the nature of their disease or through their treatment. Septic arthritis, crystal-induced arthritis (CIA), and reactive arthritis (RA) all present in a similar fashion with erythematous, edematous, painful joints. Methods A retrospective review was performed using data compiled from patient charts at the Moffitt Cancer Center between the dates of January 1, 2010, and February 22, 2018. Of the original 56 patients who had joint aspirations, 45 met the inclusion criteria of also having either a solid or hematologic malignancy. Results Analysis of the study population suggests that septic arthritis or CIA is significantly less common compared with RA in cancer patients. In addition, the development of septic arthritis is strongly associated with both prosthetic joints and nearby malignancies. Calcium pyrophosphate crystal-induced and monosodium urate CIA presents similar to septic arthritis. Lastly, synovial fluid analysis distinguishes the etiologies of arthritis more accurately compared with serum analysis. Conclusions The data collected in the study support the conclusion that oncology patients presenting with an inflamed joint are more likely to have RA and unlikely to have septic arthritis unless associated with a prosthesis or nearby malignancy. Reactive arthritis is most common and readily resolves with chemotherapy and anti-inflammatory therapy with no joint destruction and rarely recurs. Lastly, synovial fluid analysis is necessary to diagnose and/or rule out specific arthritis causes. Correspondence to: John N. Greene, MD, Infectious Diseases and Hospital Epidemiologist, Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, FOB-3, Tampa, FL 33612-9497. E-mail: John.Greene@moffitt.org. The authors of this paper have no funding or financial conflicts of interests to disclose. None of the authors have any financial ties with an organization with a financial stake in the research conducted. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2ULyvv0

Risk Factors and Outcomes of Vancomycin-Resistant Versus Vancomycin-Sensitive Enterococcal Blood Stream Infections in Patients With Acute Myeloid Leukemia

Background Studies have shown increased mortality from vancomycin-resistant enterococcal (VRE) blood stream infections (BSI) in neutropenic patients. Whether these mortality differences pertain to acute myeloid leukemia (AML) patients is unknown. We compared risk factors and outcomes between VRE and vancomycin-sensitive enterococcal (VSE) BSIs in AML patients. Methods We conducted a single-center, 5-year, retrospective cohort study of AML patients with enterococcal BSI. Neutropenia duration, Enterococcus species, vancomycin exposure, VRE colonization, 7- and 30-day mortality, age, sex, length of stay, and central line status were compared and analyzed. Results There were a total of 77 AML patients with enterococcal BSI, 54.5% had VRE. Enterococcus faecalis and Enterococcus faecium accounted for 28.5% and 62.3% of BSI, respectively. The E. faecalis isolates were more likely to be VSE (91% vs 9%, P

http://bit.ly/2SebZ0I

Frailty in patients undergoing transcatheter aortic valve implantation: a protocol for a systematic review

Introduction

Aortic stenosis is a significant cause of morbidity and mortality in older patients. The advent of transcatheter aortic valve implantation (TAVI) offers an alternative to surgical aortic valve replacement for patients with severe symptomatic aortic stenosis who are at high or intermediate risk of adverse events. Existing evidence highlights the importance of frailty as a predictor of poor outcomes post-TAVI. The objective of this study is to review the operationalisation of frailty instruments for TAVI recipients and determine clinical outcomes and the change in quality of life in frail patients undergoing TAVI.

Methods and analysis

Methods are reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 checklist. We will search relevant databases to identify published, completed but unpublished and ongoing studies. We will include studies of patients with aortic stenosis, diagnosed as frail and who underwent a TAVI procedure that report mortality, clinical outcomes or health-related quality of life. Retrospective or prospective cohort studies, randomised controlled trials and non-randomised controlled trials will be eligible for inclusion. Two researchers will independently screen articles for inclusion, with disagreements resolved by a third reviewer. One researcher will extract data with audit by a second researcher. The risk of bias in studies will be evaluated using the Quality in Prognosis Studies tool. Meta-analysis of mortality, survival curve and the change in quality of life will be performed if appropriate. Subgroup analysis, sensitivity analysis and meta-regression will be performed if necessary.

Ethics and dissemination

Due to the nature of this study, no ethical issues are foreseen. We will disseminate the results of our systematic review through a peer-reviewed journal.

Trial registration number

CRD42018090597.

http://bit.ly/2GdlSFO

Sharing individual participant data from clinical studies: a cross-sectional online survey among Italian patient and citizen groups

Objectives

To gather knowledge on the current debate, opinions and attitudes of Italian patient and citizen groups on individual participant data (IPD) sharing from clinical studies.

Design

Cross-sectional online survey.

Setting and participants

A 22-item online questionnaire was sent by email to 2003 contacts of patient and citizen groups in Italy. We received 311 responses, checked for duplicate respondents (16); 295 single groups responded, 280 providing questionnaires eligible for analysis (response rate 15%). Ninety (32.1%) dealt with oncology and palliative care, 175 (46.2%) operated locally or regionally and 136 (48.6%) were involved in clinical research.

Outcome measure

Data on Italian patient and citizen groups' self-reported knowledge, attitudes and opinions on IPD sharing, mechanisms for IPD access, advantages and risks.

Results

Half the respondents (144 out of 280, 51%) had some knowledge about the IPD sharing debate, and 60 (42%) stated they had an official position (35 in favour, 19 in favour with restrictions, 2 against, 1 neither for nor against, 3 missing). Nineteen discussed the topic encouraged by this survey; 39% approved broad access by researchers and other professions and identified information to participants, data de-identification, secure archives, access agreements and sanctions for misuse as important aspects of IPD sharing models. Respondents highlighted re-identification, privacy and re-use of data for purposes that participants do not agree on, as main risks, advancement of innovation and reducing waste in research as main advantages. Around half believed IPD sharing would not discourage study participation.

Conclusions

Half the respondents were aware of the debate. Those who had an official position were mainly in favour of IPD sharing. Many supported broad access, asking for conditions important for building trust in entities that handle IPD sharing.

Although limited by the low response rate, these findings reinforce the demand for reliable and transparent processes where accountabilities are clear.

http://bit.ly/2DeIZf5

Tuberculosis notification in a private tertiary care teaching hospital in South India: a mixed-methods study

Objectives

India contributes approximately 25% of the 'missing' cases of tuberculosis (TB) globally. Even though ~50% of patients with TB are diagnosed and treated within India's private sector, few are notified to the public healthcare system. India's TB notification policy mandates that all patients with TB are notified through Nikshay (TB notification portal). We undertook this study in a private hospital to assess the proportion notified and factors affecting TB notifications. We explored barriers and probable solutions to TB notification qualitatively from health provider's perspective.

Study setting

Private, tertiary care, teaching hospital in Bengaluru, South India.

Methodology

This was a mixed-methods study. Quantitative component comprised a retrospective review of hospital records between 1 January 2015 and 31 December 2017 to determine TB notifications. The qualitative component comprised key informant interviews and focus groups to elicit the barriers and facilitators of TB notification.

Results

Of 3820 patients diagnosed and treated, 885 (23.2%) were notified. Notifications of sputum smear-positive patients were significantly more likely, while notifications of children were less likely. Qualitative analysis yielded themes reflecting the barriers to TB notification and their solutions. Themes related to barriers were: (1) basic diagnostic procedures and treatment promote notification; (2) misconceptions regarding notification and its process are common among healthcare providers; (3) despite a national notification system other factors have prevented notification of all patients; and (4) establishing hospital systems for notification will go a long way in improving notifications.

Conclusions

The proportion of patients with TB notified by the hospital was low. A comprehensive approach both by the hospital management and the national TB programme is necessary for improving notification. This includes improving awareness among healthcare providers about the requirement for TB notifications, establishing a single notification portal in hospital, digitally linking hospital records to Nikshay and designating one person to be responsible for notification.

http://bit.ly/2DhFGnk

Pre-hospital anaesthesia and assessment of head injured patients presenting to a UK Helicopter Emergency Medical Service with a high Glasgow Coma Scale: a cohort study

Objectives

Patients who sustain a head injury but maintain a Glasgow Coma Scale (GCS) of 13–15 may still be suffering from a significant brain injury. We aimed to assess the appropriateness of triage and decision to perform prehospital rapid sequence induction (RSI) in patients attended by a UK Helicopter Emergency Medical Service (HEMS) following head injury.

Design

A retrospective cohort study of patients attended by Kent Surrey & Sussex Air Ambulance Trust (KSSAAT) HEMS.

Setting

A mixed urban and rural area of 4.5 million people in South East England.

Participants

GCS score of 13, 14 or 15 on arrival of the HEMS team and clinical findings suggesting head injury. Patients accompanied by the HEMS team to hospital ('Escorted'), and those that were 'Assisted' but conveyed by the ambulance service were reviewed. No age restrictions to inclusion were set.

Primary outcome measure

Significant brain injury.

Secondary outcome measure

Recognition of patients requiring prehospital anaesthesia for head injury.

Results

Of 517 patients, 321 had adequate follow-up, 69% of these were Escorted, 31% Assisted. There was evidence of intracranial injury in 13.7% of patients and clinically important brain injury in 7.8%. There was no difference in the rate of clinically important brain injury between Escorted and Assisted patients (p=0.46). Nineteen patients required an RSI by the HEMS team and this patient group was significantly more likely to have clinically important brain injury (p=0.04).

Conclusion

In patients attended by a UK HEMS service with a head injury and a GCS of 13–15, a small but significant proportion had a clinically important brain injury and a proportion were appropriately recognised as requiring prehospital RSI. For patients deemed not to need a HEMS intervention, differentiating between those with and without clinically important brain injury appears challenging.

Level of evidence

V.

http://bit.ly/2GdlmHS

The influence of perceived medical risks and psychosocial concerns on photoprotection behaviours among adults with xeroderma pigmentosum: a qualitative interview study in the UK

Background

A high level of photoprotection is required by people with xeroderma pigmentosum (XP), a rare skin disease, to reduce skin cancer and other risks. However poor photoprotection is thought to be widespread.

Purpose

This study examines the influences on photoprotection behaviours in adults with XP.

Design

Inductive qualitative study with semistructured interviews. Analysis employed a framework approach.

Setting

National sample recruited through a specialist XP centre in London.

Methods

Semistructured interviews at patients' homes. All transcripts were coded and themes charted for each participant. Comparisons within and across cases identified common themes and differing motivations and approaches to photoprotection. Credibility of interpretations assessed through patient/carer input and clinic adherence scores.

Participants

25 adults (17 male, eight female) aged 16–63 years with diagnosed XP attending a specialist centre. 18 lived outside London.

Results

Awareness of risks of ultraviolet radiation (UVR) and photoprotection was high. However, photoprotection behaviours varied according to perceived necessity and concerns. Three behavioural responses were identified: (1) 'dominated' by planning and routines to achieve a high level of photoprotection with significant activity restrictions and psychosocial impacts. (2) 'resistant' to photoprotection with priority given to avoiding an illness identity and enjoying a normal life. (3) Photoprotection' integrated' with an individual's life with little psychosocial impact. These responses were influenced by illness, personal and contextual factors including age, life stage and social support. Only the 'integrated' group achieved an equilibrium between perceived 'necessity' and 'concerns'.

Conclusions

The personal balance between perceived risks of UVR and social/psychological 'concerns' led to differing behavioural responses and contributes to an understanding of adaptation and normalisation in chronic illness. The study will also inform a series of individualised behavioural interventions to reduce measured UVR exposure among people with XP that are potentially applicable to other conditions with high risks of skin cancer.

http://bit.ly/2DagaAy

Family Violence Curricula in Europe (FAVICUE): a cross-sectional descriptive study protocol

Introduction

Family violence (FV) is a widespread public health problem of epidemic proportions and serious consequences. Doctors may be the first or only point of contact for victims who may be hesitant or unable to seek other sources of assistance, and they tend not to disclose abuse to doctors if not specifically asked. A comprehensive healthcare response is key to a coordinated community-wide approach to FV, but most of the practising physicians have received either no or insufficient education or training in any aspect of FV. Training of medical students concerning FV is often delivered in an inconsistent or ad hoc manner.

The main aim of this project, Family Violence Curricula in Europe (FAVICUE), is to (1) describe current FV education delivery in European medical universities (undergraduate period) and during the specialist training in general practice (GP)/family medicine (FM) (postgraduate residency programme), and (2) compare it with WHO recommendations for FV curriculum.

Methods and analysis

This is the protocol of a cross-sectional descriptive study consisting of two self-report online surveys (for undergraduate and postgraduate training, respectively) with 40 questions each. For both surveys, general practitioners, residents, medical students and professionals involved in their education from countries of the European region will be identified through the European Regional Branch of the World Organization of National Colleges, Academies and Academic Associations of General Practitioners/Family Physicians (WONCA Europe) and will be invited to provide information regarding the training on FV. Descriptive tests will be carried out and a thematic analysis will be conducted on the open-ended questions.

Ethics and dissemination

Ethics approval has been obtained by the University of Luxembourg (ERP 17–015 FAVICUE). The results will provide important information concerning current curricula on FV, and can be used for mapping the educational needs and planning the implementation of future training interventions. They will be published and disseminated through WONCA Europe and its networks.

http://bit.ly/2GdlMxW

Chronic heart failure patients experiences of German healthcare services: a protocol for a scoping review

Introduction

Chronic heart failure (CHF) is a heterogeneous condition requiring complex treatment from diverse healthcare services. An increasingly holistic understanding of healthcare has resulted in contextual factors such as perceived quality of care, as well as patients' acceptance, preferences and subjective expectations of health services, all gaining in importance. How patients with CHF experience the use of healthcare services has not been studied within the scope of a systematic review in a German healthcare context. The aim of this scoping review is therefore to review systematically the experiences of patients affected by CHF with healthcare services in Germany in the literature and to map the research foci. Further objectives are to identify gaps in evidence, develop further research questions and to inform decision makers concerned with improving healthcare of patients living with CHF.

Methods and analysis

This scoping review will be based on a broad search strategy involving systematic and comprehensive electronic database searches in MEDLINE, EMBASE, PsycINFO, PSYNDEX, CINAHL and Cochrane's Database of Systematic Reviews, grey literature searches, as well as hand searches through reference lists and non-indexed key journals. The methodological procedure will be based on an established six-stage framework for conducting scoping reviews that includes two independent reviewers. Data will be systematically extracted, qualitatively and quantitatively analysed and summarised both narratively and visually. To ensure the research questions and extracted information are meaningful, a patient representative will be involved.

Ethics and dissemination

Ethical approval will not be required to conduct this review. Results will be disseminated through a clearly illustrated report that will be part of a wider research project. Furthermore, it is intended that the review's findings should be made available to relevant stakeholders through conference presentations and publication in peer-reviewed journals (knowledge transfer). Protocol registration in PROSPERO is not applicable for scoping reviews.

http://bit.ly/2DcQqn0

Assessing the readability and patient comprehension of rheumatology medicine information sheets: a cross-sectional Health Literacy Study

Objectives

Patients are often provided with medicine information sheets (MIS). However, up to 60% of patients have low health literacy. The recommended readability level for health-related information is ≤grade 8. We sought to assess the readability of MIS given to patients by rheumatologists in Australia, the UK and Canada and to examine Australian patient comprehension of these documents.

Design

Cross-sectional study.

Setting

Community-based regional rheumatology practice.

Participants

Random sample of patients attending the rheumatology practice.

Outcome measures

Readability of MIS was assessed using readability formulae (Flesch Reading Ease formula, Simple Measure of Gobbledygook scale, FORCAST (named after the authors FORd, CAylor, STicht) and the Gunning Fog scale). Literal comprehension was assessed by asking patients to read various Australian MIS and immediately answer five simple multiple choice questions about the MIS.

Results

The mean (±SD) grade level for the MIS from Australia, the UK and Canada was 11.6±0.1, 11.8±0.1 and 9.7±0.1 respectively. The Flesch Reading Ease score for the Australian (50.8±0.6) and UK (48.5±1.5) MIS classified the documents as 'fairly difficult' to 'difficult'. The Canadian MIS (66.1±1.0) were classified as 'standard'. The five questions assessing comprehension were correctly answered by 9/21 patients for the adalimumab MIS, 7/11 for the methotrexate MIS, 6/28 for the non-steroidal anti-inflammatory MIS, 10/11 for the prednisone MIS and 13/24 for the abatacept MIS.

Conclusions

The readability of MIS used by rheumatologists in Australia, the UK and Canada exceeds grade 8 level. This may explain why patient literal comprehension of these documents may be poor. Simpler, shorter MIS with pictures and infographics may improve patient comprehension. This may lead to improved medication adherence and better health outcomes.

http://bit.ly/2GdD79Y

Alcohol consumption in Spanish primary health care providers: a national, cross-sectional study

Aim

To estimate the prevalence of alcohol consumption and analyse the drinking patterns among primary healthcare (PHC) providers.

Design

Observational, cross-sectional, descriptive study.

Setting

PHC centres in the Spanish National Health System (SNHS).

Participants

Doctors and nurses who completed an online questionnaire which explored their alcohol intake, using the Alcohol Use Disorders Identification Test (AUDIT-C) alcohol assessment tool. The study population was recruited by random sampling stratified by regions of the SNHS PHC centres.

Primary and secondary outcome measures

Frequency of alcohol consumption, number of alcohol drinks on a typical day, frequency of more than six standard drinks (SDs) intake.

Results

A total of 1760 PHC providers completed the questionnaire. The frequency of alcohol consumption was: abstention (12%, 95% CI 10.4% to 13.5%); one or less SDs/month (26%, 95% CI 23.8% to 27.9%); 2–4 SDs/month (32.2%, 95% CI 29.7% to 34.1%); 2–3 SDs/week (17.9%, 95% CI 16.0% to 19.6%); four or more SDs/week (11.9%, 95% CI 10.3% to 13.3%). The number of drinks on a typical day was: none (45.6%, 95% CI 42.9% to 47.6%); 1–2 drinks (47.3%, 95% CI 23.8% to 27.9%); 3–4 drinks (6.5%, 95% CI 5.3% to 7.6%). The percentage of hazardous drinking, according to AUDIT-C criteria, was 32% (95% CI 26.7 to 37.3), with a greater frequency of intake in older professionals (p<0.001), in contrast to a higher number of drinks consumed on a typical day by younger providers (p<0.001). Intake was higher among males (p<0.001), primary care physicians (p<0.001) and resident trainers (p<0.001).

Conclusions

Our study discloses the most up-to-date portrait of current alcohol consumption among Spanish PHC providers, showing a higher prevalence of alcohol intake, compared with the general population. Preventive strategies should be implemented to improve the awareness and training of PHC professionals towards alcohol consumption.

http://bit.ly/2DbXLDm

Public perceptions of changing the terminology for low-risk thyroid cancer: a qualitative focus group study

Objectives

To investigate public perceptions of overdiagnosis and overtreatment in low-risk thyroid cancer and explore opinions regarding the proposed strategy to change the terminology of low-risk cancers.

Design

Qualitative study using focus groups that included a guided group discussion and presentation explaining thyroid cancer, overdiagnosis and overtreatment, and proposed communication strategies. Transcripts were analysed thematically.

Setting

Sydney, Australia.

Participants

Forty-seven men and women of various ages from a range of socioeconomic backgrounds with no personal history of thyroid cancer.

Results

Participants had low pre-existing general awareness of concepts of overdiagnosis and overtreatment and expressed concern regarding this new information in relation to thyroid cancer. Overall, participants understood why the strategy to change the terminology was being proposed and could see potential benefits including reducing the negative psychological impact and stigma associated with the term 'cancer'; however, many still had reservations about the strategy. The majority of the concerns were around their worry about the risk of further disease progression and that changing the terminology may create confusion and cause patients not to take the diagnosis and its associated managements seriously. Despite varied views towards the proposed strategy, there was a strong overarching desire for greater patient and public education around overdiagnosis and overtreatment in both thyroid cancer and cancer generally in order to complement any revised terminology and/or other mitigation strategies.

Conclusions

We found a strong and apparently widely held desire for more information surrounding the topic of overdiagnosis and overtreatment. Careful consideration of how to inform both the public and current patients about the implications of a change in terminology, including changes to patients' follow-up or treatments, would be needed if such a change were to go ahead.

http://bit.ly/2GdlB5K

Dietary intervention in patients with age-related macular degeneration: protocol for a randomised controlled trial

Introduction

Age-related macular degeneration (AMD) is a leading cause of blindness. After smoking, nutrition is the key modifiable factor in reducing AMD incidence and progression, and no other preventative treatments are currently available. At present, there is an evidence–practice gap of dietary recommendations made by eye care practitioners and those actually practised by patients with AMD. To address this gap, a telephone-delivered dietary intervention tailored to patients with AMD will be piloted. The study aims to improve dietary intake and behaviours in patients with AMD. This type of nutrition-focused healthcare is currently not considered in the long-term management of AMD and represents the first empirical evaluation of a telephone-supported application encouraging adherence to dietary recommendations for AMD.

Methods and analysis

140 participants with AMD will be recruited for this randomised controlled trial. Those lacking English fluency; unwilling to engage in the intervention or provide informed consent were excluded. Following the completion of the baseline questionnaire, participants will be randomised into one of two arms: intervention or wait-list control (70 each in the intervention and control groups). Intervention participants will receive a detailed mail-delivered workbook containing information on healthy eating behaviours that promote optimal macular health, as well as scheduled phone calls over 4 months from an accredited practising dietitian. Descriptive statistics and multivariate stepwise linear regressions analyses will be used to summarise and determine the changes in dietary intakes, respectively. Economic analysis will be conducted to determine intervention feasibility and possibility of a large-scale rollout.

Ethics and dissemination

The study was approved by the University of Sydney Human Research Ethics Committee (HREC) (Reference: HREC 2018/219). Study findings will be disseminated via presentations at national/international conferences and peer-reviewed journal articles.

Trial registration number

ACTRN12618000527268; Pre-results.

http://bit.ly/2DcQqU2

Do doctors in dispensing practices with a financial conflict of interest prescribe more expensive drugs? A cross-sectional analysis of English primary care prescribing data

Objectives

Approximately one in eight practices in primary care in England are 'dispensing practices' with an in-house dispensary providing medication directly to patients. These practices can generate additional income by negotiating lower prices on higher cost drugs, while being reimbursed at a standard rate. They, therefore, have a potential financial conflict of interest around prescribing choices. We aimed to determine whether dispensing practices are more likely to prescribe high-cost options for four commonly prescribed classes of drug where there is no evidence of superiority for high-cost options.

Design

A list was generated of drugs with high acquisition costs that were no more clinically effective than those with the lowest acquisition costs, for all four classes of drug examined. Data were obtained prescribing of statins, proton pump inhibitors (PPIs), angiotensin receptor blockers (ARBs) and ACE inhibitors (ACEis). Logistic regression was used to calculate ORs for prescribing high-cost options in dispensing practices, adjusting for Index of Multiple Deprivation score, practice list size and the number of doctors at each practice.

Setting

English primary care.

Participants

All general practices in England.

Main outcome measures

Mean cost per dose was calculated separately for dispensing and non-dispensing practices. Dispensing practices can vary in the number of patients they dispense to; we, therefore, additionally compared practices with no dispensing patients, low, medium and high proportions of dispensing patients. Total cost savings were modelled by applying the mean cost per dose from non-dispensing practices to the number of doses prescribed in dispensing practices.

Results

Dispensing practices were more likely to prescribe high-cost drugs across all classes: statins adjusted OR 1.51 (95% CI 1.49 to 1.53, p<0.0001), PPIs OR 1.11 (95% CI 1.09 to 1.13, p<0.0001), ACEi OR 2.58 (95% CI 2.46 to 2.70, p<0.0001), ARB OR 5.11 (95% CI 5.02 to 5.20, p<0.0001). Mean cost per dose in pence was higher in dispensing practices (statins 7.44 vs 6.27, PPIs 5.57 vs 5.46, ACEi 4.30 vs 4.24, ARB 11.09 vs 8.19). For all drug classes, the more dispensing patients a practice had, the more likely it was to issue a prescription for a high-cost option. Total cost savings in England available from all four classes are £628 875 per month or £7 546 502 per year.

Conclusions

Doctors in dispensing practices are more likely to prescribe higher cost drugs. This is the largest study ever conducted on dispensing practices, and the first contemporary research suggesting some UK doctors respond to a financial conflict of interest in treatment decisions. The reimbursement system for dispensing practices may generate unintended consequences. Robust routine audit of practices prescribing higher volumes of unnecessarily expensive drugs may help reduce costs.

http://bit.ly/2GbnAYc

SAFETEL randomised controlled feasibility trial of a safety planning intervention with follow-up telephone contact to reduce suicidal behaviour: study protocol

Introduction

There are no evidence-based interventions that can be administered in hospital settings following a general hospital admission after a suicide attempt.

Aim

To determine whether a safety planning intervention (SPI) with follow-up telephone support (SAFETEL) is feasible and acceptable to patients admitted to UK hospitals following a suicide attempt.

Methods and analysis

Three-phase development and feasibility study with embedded process evaluation. Phase I comprises tailoring an SPI with telephone follow-up originally designed for veterans in the USA, for use in the UK. Phase II involves piloting the intervention with patients (n=30) who have been hospitalised following a suicide attempt. Phase III is a feasibility randomised controlled trial of 120 patients who have been hospitalised following a suicide attempt with a 6-month follow-up. Phase III participants will be recruited from across four National Health Service hospitals in Scotland and randomised to receive either the SPI with telephone follow-up and treatment as usual (n=80) or treatment as usual only (n=40). The primary outcomes are feasibility outcomes and include the acceptability of the intervention to participants and intervention staff, the feasibility of delivery in this setting, recruitment, retention and intervention adherence as well as the feasibility of collecting the self-harm re-admission to hospital outcome data. Statistical analyses will include description of recruitment rates, intervention adherence/use, response rates and estimates of the primary outcome event rates, and intervention effect size (Phase III). Thematic analyses will be conducted on interview and focus group data.

Ethics and dissemination

The East of Scotland Research Ethics Service (EoSRES) approved this study in March 2017 (GN17MH101 Ref: 17/ES/0036). The study results will be disseminated via peer-reviewed publication and conference presentations. A participant summary paper will also be disseminated to patients, service providers and policy makers alongside the main publication.

Trial registration number

ISRCTN62181241.

http://bit.ly/2Db20z7

Mindfulness-based and cognitive-based stress prevention in student teachers (startklar): study protocol of a randomised controlled trial

Introduction

Teachers and student teachers in Germany are a high-risk population for stress and stress-related mental health problems. This often leads to early retirement in subsequent professional life. Various trials have demonstrated positive effects of stress prevention training on the perceived stress and stress-related symptoms of teachers. Although many studies show positive effects of mindfulness-based stress interventions, there is not yet any mindfulness-based intervention for teachers or student teachers in Germany. The aim of this trial is to evaluate a training that combines mindfulness-based and cognitive interventions into one programme, addressing to the specific burdens of student teachers.

Methods and analysis

This study protocol presents a prospective block-randomised controlled trial. Assessment will take place at three time points (baseline, post-intervention, 3-month follow-up) for an intervention and waiting control group, and at a fourth assessment point for the waiting control group after receiving the training. The aim is to evaluate the effects of mindfulness-based stress prevention on stress, psychological morbidity, burnout and self-efficacy using validated measures. Participants are student teachers from German teacher training colleges and participation will be voluntary. The targeted total sample size is 96 at 3-month follow-up. The training will comprise three 4-hour sessions conducted every 2 weeks. The control group will participate in the training after the 3-month follow-up. The allotment will be randomised with a stratified allocation ratio by gender. After descriptive statistics have been evaluated, inferential statistical analysis will be conducted using repeated measures analysis of variance with interactions between time and group. Effect sizes will be calculated using partial ² values.

Ethics and dissemination

Results will be disseminated at conferences, in specialist magazines and through peer-reviewed publications. The trial has been approved by the ethics review board of the local medical association, Mainz, Germany, under the reference number 837.192.16 (10511).

Trial registration number

DRKS00010897.

http://bit.ly/2GdlwPu

Guidance for reporting outcomes in clinical trials: scoping review protocol

Introduction

Patients, families and clinicians rely on published research to help inform treatment decisions. Without complete reporting of the outcomes studied, evidence-based clinical and policy decisions are limited and researchers cannot synthesise, replicate or build on existing research findings. To facilitate harmonised reporting of outcomes in published trial protocols and reports, the Instrument for reporting Planned Endpoints in Clinical Trials (InsPECT) is under development. As one of the initial steps in the development of InsPECT, a scoping review will identify and synthesise existing guidance on the reporting of trial outcomes.

Methods and analysis

We will apply methods based on the Joanna Briggs Institute scoping review methods manual. Documents that provide explicit guidance on trial outcome reporting will be searched for using: (1) an electronic bibliographic database search; (2) a grey literature search; and (3) solicitation of colleagues for guidance documents using a snowballing approach. Reference list screening will be performed for included documents. Search results will be divided between two trained reviewers who will complete title and abstract screening, full-text screening and data charting. Captured trial outcome reporting guidance will be compared with candidate InsPECT items to support, refute or refine InsPECT content and to assess the need for the development of additional items. Data analysis will explore common features of guidance and use quantitative measures (eg, frequencies) to characterise guidance and its sources.

Ethics and dissemination

A paper describing the review findings will be published in a peer-reviewed journal. The results will be used to inform the InsPECT development process, helping to ensure that InsPECT provides an evidence-based tool for standardising trial outcome reporting.

http://bit.ly/2Gdlt6g

Cross-sectional study of the association between serum perfluorinated alkyl acid concentrations and dental caries among US adolescents (NHANES 1999-2012)

Study objectives

Perfluoroalkyl acids (PFAAs) are a class of anthropogenic and persistent compounds that may impact some biological pathways related to oral health. The objective of our study was to estimate the relationship between dental caries prevalence and exposure to four PFAA: perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS) and perfluorooctane sulfonic acid (PFOS) in a nationally representative sample of US adolescents.

Setting/Design

We analysed cross-sectional data from the National Health and Nutrition Examination Survey from 1999 to 2012 for 12–19-year-old US adolescents.

Participants

Of 10 856 adolescents aged 12 to 19 years who had a dental examination, we included 2869 with laboratory measurements for serum PFAA concentrations and complete covariate data in our study.

Primary and secondary outcome measures

Dental caries prevalence was defined as the presence of decay or a restoration on any tooth surface, or the loss of a tooth due to tooth decay. We used multivariable logistic regression to estimate the covariate-adjusted association between serum PFAA concentrations and dental caries prevalence, accounting for the complex National Health and Nutrition Examination Survey design.

Results

Of 2869 adolescents, 59% had one or more dental caries. We observed no associations between the prevalence of dental caries and serum concentrations of PFOA, PFOS or PFHxS. The adjusted odds of caries were 21% (OR 0.79; 95% CI 0.63 to 1.01), 15% (OR 0.85; 95% CI 0.67 to 1.08) and 30% (OR 0.7; 95% CI 0.55 to 0.90) lower among adolescents in the 2nd, 3rd and 4th serum PFNA concentration quartiles compared to adolescents in the first quartile, respectively. The linear trend for this association was not statistically significant.

Conclusion

PFOA, PFOS and PFHxS were not associated with prevalence of dental caries. The prevalence of caries was reduced with increasing serum PFNA concentrations; however, these results should be interpreted cautiously given that we were unable to adjust for several factors related to oral health.

http://bit.ly/2DbXHU8

Improving neurodevelopmental outcomes in children with congenital heart disease: protocol for a randomised controlled trial of working memory training

Introduction

Executive function (EF) impairments are among the most prevalent neurodevelopmental morbidities in youth with congenital heart disease (CHD). To date, no studies have investigated the efficacy of cognitive interventions to improve EF outcomes in children with CHD.

Methods and analysis

This is a single-centre, single-blinded, two-arm randomised controlled trial to test the efficacy of Cogmed Working Memory Training (Cogmed) versus standard of care in children with CHD after open-heart surgery in infancy. Participants will consist of 100 children with CHD aged 7–12 years who underwent open-heart surgery before the age of 12 months. Participants are randomly allocated to either an intervention group including training on the home-based Cogmed intervention for a duration of approximately 5 weeks or a control group who receive the standard of care. We will evaluate the efficacy of Cogmed at post-treatment and 3 months after completion of the intervention. Baseline, post-treatment and 3-month follow-up assessments will include specific measures of EF, cognitive and social functioning, and attention deficit hyperactivity disorder (ADHD) symptoms. The primary outcome of this study is the change in standardised mean score on the List Sorting Working Memory test from the National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function. Secondary outcomes include measures of social skills, inhibitory control, cognitive flexibility and behavioural EF as well as ADHD symptoms as measured by the Behavior Rating Inventory of Executive Function, Second Edition, and the Conners Third Edition. The efficacy of the intervention will be evaluated by comparing within-subject differences (baseline to post-treatment, baseline to 3-month follow-up) between the two groups using an intention-to-treat analysis.

Ethics and dissemination

This study has received Institutional Review Board (IRB) approval from Boston's Children's Hospital IRB (P00022440) and the Human Protection Agency from the US Department of Defense.

Trial registration number

NCT03023644; Pre-results.

http://bit.ly/2Gdlrva

Factors associated with receiving surgical treatment for menorrhagia in England and Wales: findings from a cohort study of the National Heavy Menstrual Bleeding Audit

Objective

To examine the factors associated with receiving surgery for heavy menstrual bleeding (HMB) in England and Wales.

Design

National cohort study.

Setting

National Health Service hospitals.

Participants

Women with HMB aged 18–60 who had a new referral to secondary care.

Methods

Patient-reported data linked to administrative hospital data. Risk ratios (RR) estimated using multivariable Poisson regression.

Primary outcome measure

Surgery within 1 year of first outpatient clinic visit.

Results

14 545 women were included. At their first clinic visit, mean age was 42 years, mean symptom severity score was 62 (scale ranging from 0 (least) to 100 (most severe)), 73.9% of women reported having symptoms for >1 year and 30.4% reported no prior treatment in primary care. One year later, 42.6% had received surgery. Of these, 57.8% had endometrial ablation and 37.2% hysterectomy. Women with more severe symptoms were more likely to have received surgery (most vs least severe quintile, 33.1% vs 56.0%; RR 1.6, 95% CI 1.5 to 1.7). Surgery was more likely among those who reported prior primary care treatment compared with those who did not (48.0% vs 31.1%; RR 1.5, 95% CI 1.4 to 1.6). Surgery was less likely among Asian and more likely among black women, compared with white women. Surgery was not associated with socioeconomic deprivation.

Conclusions

Receipt of surgery for HMB depends on symptom severity and prior treatment in primary care. Referral pathways should be locally audited to ensure women with HMB receive care that addresses their individual needs and preferences, especially for those who do not receive treatment in primary care.

http://bit.ly/2Df2uV3

Researcher allegiance in research on psychosocial interventions: meta-research study protocol and pilot study

Introduction

One potential source of bias in randomised clinical trials of psychological interventions is researcher allegiance (RA). The operationalisation of RA differs strongly across studies, and there is not a generally accepted method of operationalising or measuring it. Furthermore, it remains unclear as to how RA affects the outcomes of trials and if it results in better outcomes for a preferred intervention. The aim of this project is to develop and validate a scale that accurately identifies RA, contribute to the understanding of the impact that RA has in a research setting and to make recommendations for addressing RA in practice.

Methods and analysis

A scale will first be developed and validated to measure RA in psychotherapy trials. The scale will be validated by surveying authors of psychotherapy trials to assess their opinions, beliefs and preferences of psychotherapy interventions. Furthermore, the scale will be validated for use outside the field of psychotherapy. The validated checklist will then be used to examine two potential mechanisms of how RA may affect outcomes of interventions: publication bias (by assessing grants) and risk of bias (RoB). Finally, recommendations will be developed, and a feasibility study will be conducted at a national mental health agency in The Netherlands. Main analyses comprise inter-rater reliability of checklist items, correlations to examine the relationship between checklist items and author survey (convergent validity) as well as checklist items and trial outcomes and multivariate meta-regression techniques to assess potential mechanisms of how allegiance affects trial outcomes (publication bias and RoB).

Ethics and dissemination

This study has been reviewed and approved by the Scientific and Ethical Review Board (VCWE) at the Vrije Universiteit Amsterdam. Study result and advancements will also be published on the Open Science Framework. Furthermore, main findings will be disseminated through articles in international peer-reviewed open access journals. Results and recommendations will be communicated to the Cochrane Collaboration, the Campbell Collaboration and other funding agencies.

http://bit.ly/2DcPejH

Undisclosed financial ties between guideline writers and pharmaceutical companies: a cross-sectional study across 10 disease categories

Objectives

To investigate the proportion of potentially relevant undisclosed financial ties between clinical practice guideline writers and pharmaceutical companies.

Design

Cross-sectional study of a stratified random sample of Australian guidelines and writers.

Setting

Guidelines available from Australia's National Health and Medical Research Council guideline database, 2012–2014, stratified across 10 health priority areas.

Population

402 authors of 33 guidelines, including up to four from each area, dependent on availability: arthritis/musculoskeletal (3); asthma (4); cancer (4); cardiovascular (4); diabetes (4); injury (3); kidney/urogenital (4); mental health (4); neurological (1); obesity (1). For guideline writers with no disclosures, or who disclosed no ties, a search of disclosures in the medical literature in the 5 years prior to guideline publication identified potentially relevant ties, undisclosed in guidelines. Guidelines were included if they contained recommendations of medicines, and writers included if developing or writing guidelines.

Main outcome measures

Proportions of guideline writers with potentially relevant undisclosed financial ties to pharmaceutical companies active in the therapeutic area; proportion of guidelines including at least one writer with a potentially relevant undisclosed tie.

Results

344 of 402 writers (86%; 95% CI 82% to 89%) either had no published disclosures (228) or disclosed they had no ties (116). Of the 344 with no disclosed ties, 83 (24%; 95% CI 20% to 29%) had potentially relevant undisclosed ties. Of 33 guidelines, 23 (70%; 95% CI 51% to 84%) included at least one writer with a potentially relevant undisclosed tie. Writers of guidelines developed and funded by governments were less likely to have undisclosed financial ties (8.1%vs30.6%; risk ratio 0.26; 95% CI 0.13 to 0.53; p<0.001).

Conclusions

Almost one in four guideline writers with no disclosed ties may have potentially relevant undisclosed ties to pharmaceutical companies. These data confirm the need for strategies to ensure greater transparency and more independence in relationships between guidelines and industry.

http://bit.ly/2Sxxjhd

Modulatory effects of miracle fruit ethanolic extracts on glucose uptake through the insulin signaling pathway in C2C12 mouse myotubes cells

Miracle fruit can efficaciously modulate diabetes, via upregulated the expression of IR‐PI3K and GLUT4 and then increased the glucose uptake ability of muscle cells.

Abstract

Miracle fruit, Synsepalum dulcificum, is commonly known to be an alternative sweetener. It makes sour food taste sweet by affecting the tongue's taste receptors. It also shows beneficial health effects, such as antioxidant, anti‐inflammatory, and antihyperglycemic activities. This study was conducted to investigate the antidiabetic effects of miracle fruit flesh (MF) and seed (MS) ethanolic extracts and the underlying mechanisms. Differentiated C2C12 myotubes were treated with the MF or MS extract (1–1,000 μg/ml) or metformin (1 mM) in the presence or absence of insulin. Compared with metformin, the MF extract significantly increased the intake of 2‐(N‐(7‐nitrobenz‐2‐oxa‐1, 3‐diazol‐4‐yl) amino)‐2‐deoxyglucose (2‐NBDG). The MF extract also upregulated insulin receptor, phosphatidylinositol 3‐kinase, and glucose transporter 4 expressions. These results reveal the antidiabetic effects of miracle fruit.

http://bit.ly/2GcyZqQ

Triacylglycerol, fatty acid, and phytochemical profiles in a new red sorghum variety (Ji Liang No. 1) and its antioxidant and anti‐inflammatory properties

The present study demonstrated the triacylglycerol composition of red sorghum oil for the first time and indicated that the new red sorghum variety may serve as a potential dietary source for unsaturated fatty acids and other beneficial phytochemicals, such as tocopherols, carotenoids, and phenolic compounds, therefore contributing to its antioxidant and anti‐inflammatory properties.

Abstract

In this study, a new red sorghum variety (Ji Liang No. 1) was investigated for its triacylglycerol (TAG) and fatty acid profiles, carotenoid and tocopherol compositions, total phenolic, total flavonoid and phenolic acid contents, and antioxidant and anti‐inflammatory properties. A total of 17 TAGs were identified in the red sorghum oil. Linoleic and oleic acids were the primary fatty acids, contributing more than 80% of the total fatty acids. β‐Carotene was the primary carotenoid at a level of 26.14 μg/g. α‐, γ‐, and δ‐tocopherols were at levels of 0.19, 4.08, and 0.10 μg/g, respectively. Moreover, acetone–water (60:40, v/v) extract of the red sorghum exhibited the greatest total phenolic content of 2.77 mg GAE/g and total flavonoid content of 5.44 mg RE/g. The extract had scavenging capacities against DPPH, ABTS⁺, and peroxyl radicals and suppressed LPS stimulated IL‐1β, IL‐6, and COX‐2 mRNA expressions in a dose‐dependent manner. Ferulic, p‐coumaric, isoferulic, and p‐hydroxybenzoic acids were found in the red sorghum, with ferulic acid as the predominant phenolic acid and mostly in an insoluble bound form. These data indicated a potential utilization of the red sorghum in health‐promoting functional food or supplemental products.

http://bit.ly/2DeEzF1

Refined cottonseed oil as a replacement for soybean oil in broiler diet

The objective of this study was to evaluate the potential of refined cottonseed oil (CSO) as a replacement for soybean oil (SBO) in broiler diets. The results showed that replacing 50% of SBO (w/w) with refined CSO in the basal diet increased broiler growth performance during the finisher period. Meanwhile, refined CSO supplementation also enhanced the serum antioxidant status. However, dietary high‐level refined CSO increased the proportions of saturated fatty acids but decreased the unsaturated fatty acids (including n‐6 PUFAs) in breast muscles of broilers. Overall, the SBO could be replaced with refined CSO up to 50% in diets for broilers without adverse effects.

Abstract

With the shortage of common vegetable fat sources, such as soybean oil (SBO), it is urgent to find alternative oil sources for broiler producers. The objective of this study was to evaluate the potential of refined cottonseed oil (CSO) as a replacement for SBO in broiler diets. A total of 180 chickens at 1 d of age were randomly assigned to five treatments of six replicates. One treatment was the basal diet (control), and the other four experimental diets were formulated from the basal diet by replacing (w/w) 25%, 50%, 75%, and 100% of the SBO with refined CSO (only containing 0.2% cyclopropenoid fatty acids, and no free gossypol was detected). At the end of week 6, blood samples were obtained from the jugular vein and the breast muscle was aseptically isolated from two birds per replicate. The results showed that substitution of CSO for low‐level SBO had no significant effect (p > 0.05) on broiler performance during the starter period (week 1–3), while 50% level of CSO inclusion significantly increased (p < 0.05) ADG and improved FCR compared with the control group during the finisher period (week 4–6). Broilers fed 100% CSO diets had lower (p < 0.05) levels of serum total protein (TP), albumin (ALB), cholesterol (CHO) concentrations, and serum alkaline phosphatase (AKP) activity than that of the control broilers. Furthermore, the serum antioxidant status appeared to be enhanced by CSO. Additionally, high levels of CSO (75 and 100%) significantly increased the proportions of C14:0 and C18:0 but decreased the proportions of C18:1n9t, C18:2n6c, and ∑ n‐6 polyunsaturated fatty acids in breast muscles of broilers. Overall, the SBO could be replaced with refined CSO up to 50% in diets for broilers without adversely affecting the performance, liver functions, and breast muscle fatty acid composition of these broilers.

http://bit.ly/2GdzAse

Overall survival, costs and healthcare resource use by number of regimens received in elderly patients with newly diagnosed metastatic triple negative breast cancer

Future Oncology, Ahead of Print.


http://bit.ly/2SqGhNl

Cannabinoids: the lows and the highs of chemotherapy-induced nausea and vomiting

Future Oncology, Ahead of Print.


http://bit.ly/2GsEr7Z

A mucosal incision assisted biopsy vs. endoscopic ultrasound‐guided fine‐needle aspiration with a rapid on‐site evaluation for gastric subepithelial lesions: A randomized crossover study

Abstract

Objectives

This study aimed to compare the diagnostic yield of mucosal incision‐assisted biopsy (MIAB) and endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) with a rapid on‐site evaluation (ROSE) for gastric subepithelial lesions (SELs) suspected of being gastrointestinal stromal tumors (GISTs) with an intraluminal growth pattern.

Methods

This was a prospective randomized crossover, multicenter study. The primary outcome was the diagnostic yield of EUS‐FNA and MIAB. The secondary outcomes were the technical success rate, complication rate, procedure time, and biopsy frequency.

Results

A total of 47 patients were randomized to the MIAB group (n=23) and EUS‐FNA group (n=24). There was no significant difference in the diagnostic yield of MIAB and EUS‐FNA (91.3% vs. 70.8%; P=0.0746). The complication rates of MIAB and EUS‐FNA did not differ to a statistically significant extent. The mean procedure time in the MIAB group was significantly longer than that in the EUS‐FNA group (34 min vs. 26 min; p=0.0011).

Conclusion

The diagnostic yield of MIAB was satisfactorily as high as EUS‐FNA with ROSE for gastric SELs with an intraluminal growth pattern.

Keywords

endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA), gastrointestinal stromal tumor (GIST), mucosal incision assisted biopsy (MIAB), randomized trial, rapid on‐site evaluation (ROSE)

This article is protected by copyright. All rights reserved.

http://bit.ly/2WMqWWP

Testes Proteases Expression and Hybrid Male Sterility Between Subspecies of Drosophila pseudoobscura

Hybrid male sterility (HMS) is a form of postmating postzygotic isolation among closely related species that can act as an effective barrier to gene flow. The Dobzhansky-Muller model provides a framework to explain how gene interactions can cause HMS between species. Genomics highlights the preponderance of non-coding DNA targets that could be involved in gene interactions resulting in gene expression changes and the establishment of isolating barriers. However, we have limited knowledge of changes in gene expression associated with HMS, gene interacting partners linked to HMS, and whether substitutions in DNA regulatory regions (cis) causes misexpression (i.e. expression of genes beyond levels found in parental species) of HMS genes in sterile hybrids. A previous transcriptome survey in a pair of D. pseudoobscura species found male reproductive tract (MRT) proteases as the largest class of genes misregulated in sterile hybrids. Here we assay gene expression in backcross (BC) and introgression (IG) progeny, along with site of expression within the MRT, to identify misexpression of proteases that might directly contribute to HMS. We find limited evidence of an accumulation of cis-regulatory changes upstream of such candidate HMS genes. The expression of four genes was differentially modulated by alleles of the previously characterized HMS gene Ovd.

http://bit.ly/2RHWWaL

Evidence for an Integrated Gene Repression Mechanism Based on mRNA Isoform Toggling in Human Cells

We recently described an unconventional mode of gene regulation in budding yeast by which transcriptional and translational interference collaborate to down-regulate protein expression. Developmentally timed transcriptional interference inhibited production of a well translated mRNA isoform and resulted in the production of an mRNA isoform containing inhibitory upstream open reading frames (uORFs) that prevented translation of the main ORF. Transcriptional interference and uORF-based translational repression are established mechanisms outside of yeast, but whether this type of integrated regulation was conserved was unknown. Here we find that, indeed, a similar type of regulation occurs at the locus for the human oncogene MDM2. We observe evidence of transcriptional interference between the two MDM2 promoters, which produce a poorly translated distal promoter-derived uORF-containing mRNA isoform and a well-translated proximal promoter-derived transcript. Down-regulation of distal promoter activity markedly up-regulates proximal promoter-driven expression and results in local reduction of histone H3K36 trimethylation. Moreover, we observe that this transcript toggling between the two MDM2 isoforms naturally occurs during human embryonic stem cell differentiation programs.

http://bit.ly/2WLX90q

Hypoxic Tumors Share Genomic Instability [News in Brief]

Changes in miRNA, copy number among commonalities.

http://bit.ly/2UKMSzG

Venus flytrap microbiotas withstand harsh conditions during prey digestion

ABSTRACT

The carnivorous Venus flytrap (Dionaea muscipula) overcomes environmental nutrient limitation by capturing small animals. Such prey is digested with an acidic enzyme-containing mucilage that is secreted into the closed trap. However, surprisingly little is known about associations with microorganisms. Therefore, we assessed microbiotas of traps and petioles for the Venus flytrap by 16S amplicon meta-barcoding. We also performed time-series assessments of dynamics during digestion in traps and experimental acidification of petioles. We found that the traps hosted distinct microbiotas that differed from adjacent petioles. Further, they showed a significant taxonomic turnover during digestion. Following successful catches, prey-associated bacteria had strong effects on overall composition. With proceeding digestion, however, microbiotas were restored to compositions resembling pre-digestion stages. A comparable, yet less extensive shift was found when stimulating digestion with coronatine. Artificial acidification of petioles did not induce changes towards trap-like communities. Our results show that trap microbiota were maintained during digestion despite harsh conditions and recovered after short-term disturbances through prey microbiota. This indicates trap-specific and resilient associations. By mapping to known genomes, we predicted putative adaptations and functional implications for the system, yet direct mechanisms and quantification of host benefits, like the involvement in digestion, remain to be addressed.

http://bit.ly/2WMxKDs

Composition of the cutaneous bacterial community of a cave amphibian, Proteus anguinus

ABSTRACT

The European cave salamander Proteus anguinus is a charismatic amphibian endemic to the concealed and inaccessible subterranean waters of the Dinaric Karst. Despite its exceptional conservation importance not much is known about its ecology and interactions with the groundwater microbiome. The cutaneous microbiota of amphibians is an important driver of metabolic capabilities and immunity, and thus a key factor in their wellbeing and survival. We used high-throughput 16S rRNA gene sequencing based on seven variable regions to examine the bacteriome of the skin of five distinct evolutionary lineages of P. anguinus and in their groundwater environment. The skin bacteriomes turned out to be strongly filtered subsamples of the environmental microbial community. The resident microbiota of the analyzed individuals was dominated by five bacterial taxa. Despite an indicated functional redundancy, the cutaneous bacteriome of P. anguinus presumably provides protection against invading microbes by occupying the niche, and thus could serve as an indicator of health status. Besides conservation implications for P. anguinus, our results provide a baseline for future studies on other endangered neotenic salamanders.

http://bit.ly/2REoJZv

Met inhibition revokes IFNγ-induction of PD-1 ligands in MET-amplified tumours

Met inhibition revokes IFNγ-induction of PD-1 ligands in MET-amplified tumours

Met inhibition revokes IFNγ-induction of PD-1 ligands in MET-amplified tumours, Published online: 06 February 2019; doi:10.1038/s41416-018-0315-3

Met inhibition revokes IFNγ-induction of PD-1 ligands in MET-amplified tumours

https://go.nature.com/2WSkSfo

Oestrogen receptor status and survival in women with BRCA2-associated breast cancer

Oestrogen receptor status and survival in women with BRCA2-associated breast cancer

Oestrogen receptor status and survival in women with BRCA2-associated breast cancer, Published online: 06 February 2019; doi:10.1038/s41416-019-0376-y

Oestrogen receptor status and survival in women with BRCA2-associated breast cancer

https://go.nature.com/2REA8IJ

Radiologists Can Help ID Intimate Partner Violence

TUESDAY, Feb. 5, 2019 -- Victims of intimate partner violence (IPV) undergo more imaging procedures than age- and sex-matched control patients and are more likely to have obstetric-gynecologic findings and acute fractures, according to a study...

http://bit.ly/2WL3qJr

Hemodialysis Facility Practices Linked to Patient Outcomes

TUESDAY, Feb. 5, 2019 -- Certain practices in hemodialysis facilities relating to management of fluid volume and intradialytic hypotension are associated with patient outcomes, according to a study published online Feb. 5 in the Clinical Journal of...

http://bit.ly/2RJDYQQ

Reading, Math Scores No Different for Children With T1DM

TUESDAY, Feb. 5, 2019 -- Standardized reading and mathematics scores do not differ significantly for public schoolchildren with and without type 1 diabetes, according to a study published in the Feb. 5 issue of the Journal of the American Medical...

http://bit.ly/2WL3pFn

USPSTF Still Recommends Against Pancreatic Cancer Screening

TUESDAY, Feb. 5, 2019 -- The U.S. Preventive Services Task Force (USPSTF) recommends against screening for pancreatic cancer in asymptomatic adults. These findings form the basis of a draft recommendation statement published online Feb. 5 by the...

http://bit.ly/2RLyWUg

California Bill Would Tighten Controls on Children's Genitalia Surgery

TUESDAY, Feb. 5, 2019 -- A bill that would place more restrictions on children's genitalia surgery in California raises serious concerns among doctors in the state. Under the bill, doctors would not be able to treat or perform surgery on children...

http://bit.ly/2WJFnL7

Decreasing Endoscopy No-Shows using Lean Improvement Framework

http://bit.ly/2WH6EO9

Preparing for Large-Scale Disruptions In Health Care Delivery: Nursing Strikes and Beyond

http://bit.ly/2RHwFJI

Classical features of Zollinger-Ellison syndrome, in images

http://bit.ly/2HRByQA

Met inhibition revokes IFNγ-induction of PD-1 ligands in MET-amplified tumours

https://go.nature.com/2RJtqBe

Oestrogen receptor status and survival in women with BRCA2-associated breast cancer

https://go.nature.com/2WJxdCt

Individualization of Clinical Target Volume Delineation Based on Stepwise Spread of Nasopharyngeal Carcinoma: Outcome of More Than a Decade of Clinical Experience

Radiation-related toxicity in nasopharyngeal carcinoma (NPC) is common. There are no well-established guidelines for clinical target volume (CTV) delineation with long-term follow-up. Current consensus continues to rely heavily on bony landmarks and fixed margins around the gross tumor volume (GTV), an approach used to define fields in the conventional 2- and 3-dimensional radiation therapy era.

http://bit.ly/2RHmKDY

To Treat, or Not to Treat, That is the Question for a 13-Month-Old Girl with Cranial Ependymoma and an Unknown Spinal Mass

The patient is a 13-month-old girl diagnosed with anaplastic ependymoma (World Health Organization grade 3). A presurgical magnetic resonance imaging (MRI) scan with and without contrast at an outside hospital revealed a 3.5 × 2.1 × 3.5 cm enhancing lesion located infratentorially with extension to the level of the C1 arch and through the right foramen of Luschka, moderate hydrocephalus, and no evidence of spinal involvement (eg, drop metastasis) (Fig. 1). A craniotomy was performed and revealed the mass to be attached to the floor of the fourth ventricle.

http://bit.ly/2WIp9BY

The Management of Colorectal Cancer Liver Metastases: The Interventional Radiology Viewpoint

"Comparison of Stereotactic Body Radiation Therapy and Radiofrequency Ablation in the Treatment of Intrahepatic Metastases" by Jackson et al is a thought-provoking addition to the literature concerning treatment of colorectal cancer metastasis (CLM). The benefits of hepatic CLM resection are well established; however, most patients are not candidates for resection. Local tumor ablation is a safe and effective alternative treatment for select patients. Considerable research has evaluated percutaneous ablation as treatment of CLM, including retrospective reviews with long-term follow-up and prospective randomized trials showing prolongation of progression-free and patient survival compared with chemotherapy alone.

http://bit.ly/2RJoVXm

Treatment of WHO Grade 2 and 3 Gliomas With Potentially Favorable Survival: Is Monotherapy Obsolete?

Previous central nervous system oncology scans in this publication have discussed management and molecular characterization of low-grade gliomas, (1) treatment strategies for high-grade gliomas in the elderly, (2) emerging treatment options for glioblastoma (GBM), (3) and molecular characterization of gliomas (4). Similar to trends observed in other oncologic diseases, grading gliomas by their molecular characteristics is emerging as a useful tool for identifying patients with potentially long-term survival after treatment of this disease.

http://bit.ly/2WJkIqA

Why Have So Few Radiation Oncologists Become U.S. or Canadian Medical School Deans or University Presidents?

There are 168 MD-granting schools of medicine in the United States and Canada.1 None currently has a radiation oncologist as dean.2 In the history of the United States and Canada, to my knowledge, 3 radiation oncologists have served as permanent (not interim) deans of a medical school: Samuel Hellman, MD, dean of the Pritzker School of Medicine, University of Chicago, 1988 to 1993; Allen S. Lichter, MD, dean of the School of Medicine, University of Michigan, 1998 to 2006; and Edward C. Halperin MD, MA, dean of the School of Medicine, University of Louisville, 2006 to 2012.

http://bit.ly/2REagNb

In Reply to Loganadane et al

To the Editor: We would like to thank Loganadane et al for their interest in our article.1,2 As stated in their letter, fecal incontinence (FI) after radiation therapy has been a widely underestimated side effect for a long time and has received attention only in the last few years.3

http://bit.ly/2WJkC2c

Aggressive Focal Therapy

In this interesting case of a 13-month-old girl with anaplastic ependymoma, the potential complicating finding of a new spinal mass may affect prognosis and current treatment paradigm.1 It is important to note that the appropriate workup was performed at the time of diagnosis and reviewed by the treating team; workup did not reveal any distant disease. However, with its high proliferative rate and tendency to disseminate into the cerebrospinal fluid, suspicious findings in the surgically unexplored neuro-axis, most commonly in the lumbosacral spine, are not uncommon in anaplastic disease.

http://bit.ly/2RGVEN7

Image Guided Evolution of Nodal Contouring Guidelines in Breast Cancer

External beam radiation therapy for breast cancer is administered to reduce locoregional recurrences, but there is increasing evidence that radiation therapy can also improve survival. The MA.201 and the European Organisation for Research and Treatment of Cancer2 trials demonstrated improved disease-free survival in patients with breast cancer receiving regional nodal irradiation, even in early stage patients with higher risk disease. However, external beam radiation therapy for breast cancer can also cause toxicity.

http://bit.ly/2WM5zEL

Chemotherapy to Spare Cognition

In this 13-month-old girl with anaplastic ependymoma, biopsy of the suspicious mass is strongly recommended because treatment varies significantly if the disease has metastasized.1 If this mass is benign, we recommend radiation to the primary tumor bed with 5 mm clinical target volume and 3 mm planning target volume margins using proton therapy to a total dose of 54 Gy (relative biological effectiveness) (Fig. 1). If the spinal disease is biopsy-proven metastatic ependymoma, there are several options, though none ideal.

http://bit.ly/2RGPi0f

In Regard to Cicchetti et al

To the Editor: We congratulate Cicchetti et al for their recent publication on the external validation of the model predicting late fecal incontinence (FI).1 This report represents one of the few studies to address FI after radiation therapy in prostate cancer. Less frequently reported than other toxicities, FI represents one of the most quality-of-life–impairing symptoms. This study aimed to validate a predictive model for late FI by Rancati et al.2

http://bit.ly/2WGXWPX

Meetings

March 14-16, 2019

http://bit.ly/2RJaJxI

Carolina Hurricanes

To the Editor: Radiation therapy (RO) in times of disasters has recently garnered much interest among those in the specialty, and the Red Journal recently devoted an edition to it.1 We felt compelled to observe that hurricanes, with their associated flooding that poses a particular threat to RO departments, are neither rare nor sudden events. From 1851 to 2017, there were 286 direct hurricane hits on the mainland of Florida, Texas, Louisiana, and North Carolina (NC) alone (∼1.7 hurricanes/year).

http://bit.ly/2WM5m4r

Issue Highlights

Rice et al and Barry et al

http://bit.ly/2RIztWK

The Value of Surgical Exposure in Radiation Oncology Training

To the Editor: Radiation oncology residents are in a unique position to experience 1 year in a specialty separate from their own before beginning an integrated program. A broad knowledge base encompassing medical oncology, surgery, and radiology is necessary for radiation oncology training; postgraduate year 2 residents often enter with the same clinical expectations as senior-level residents. However, presently, very little time is dedicated to meaningful surgical exposure in medical school and preliminary/transitional year programs.

http://bit.ly/2WIqxV7

In Regard to Borm et al

To the Editor: We read with great interest the article by Borm et al on the lymph node atlas in breast cancer based on fluorodeoxyglucose-positron emission tomography.1 The authors should be commended for their laborious task of contouring lymph nodes and their high-quality analysis. They analyzed lymph node metastasis patterns based on contouring guidelines of the Radiation Therapy Oncology Group and the European Society for Radiotherapy and Oncology (ESTRO)2,3 and concluded that neither adequately covers lymph node metastasis.

http://bit.ly/2RESl9i

Biopsy First, CSI Much Much Later

This case of a 13-month-old girl with an anaplastic ependymoma illustrates the complexities involved in the management of pediatric brain tumors, specifically the interpretation of spinal imaging and decisions regarding optimal therapy in a young and developing 13-month-old child.1

http://bit.ly/2WKmlUU

The Management of Colorectal Cancer Liver Metastases: The Radiation Oncology Viewpoint

Advances in technical precision and shortened treatment time in radiation therapy have established stereotactic body radiation therapy (SBRT) as an effective treatment option for oligometastatic disease. Liver SBRT has been shown to have a positive effect on patients' quality of life,1 local control (LC),2,3 and potentially overall survival.4

http://bit.ly/2RESjhG

Genetics of bronchopulmonary dysplasia: When things do not match up, it is only the beginning

Parad et al1 speculate that, for extremely preterm infants, the roles of "immature lung structure and biochemical status" may trump genetic factors in bronchopulmonary dysplasia (BPD). Based on sample differences with previous twin studies, they propose that "if a genetic predisposition to BPD exists, it could play a more important role in infants born at or over 29 weeks gestational age."1

http://bit.ly/2Tzzuhx

Digital Amputation by Congenital Insensitivity to Pain with Anhidrosis

An 18-month-old boy was referred to the pediatric neurology clinic for evaluation of finger ulcers. He was born to nonconsanguineous parents with uncomplicated delivery. Detailed history revealed early dislocation of his first teeth, easy fatigability in summer, and autistic trait. On examination, the first and second digits of both hands were amputated distally (Figure). His palms were warm and dry. Thermal sweating test revealed complete anhidrosis. Palmar sympathetic skin response was not seen.

http://bit.ly/2BwmvX9

Vesical Hemangioma in a Patient with Klippel-Trenaunay-Weber Syndrome

A 3-year-old child with Klippel-Trepanauy-Weber syndrome (KTWS), was admitted to our hospital with recurrent episodes of hematuria. Subsequent clinical history revealed 2 episodes of hematuria some weeks before, not initially mentioned by the parents. Urine analyses were negative for erythrocytes and proteinuria. The child manifested a normocytic anemia (hemoglobin, 9.9 g/dL; mean corpuscular volume, 74 μm3; iron, 13 μg/d). Coagulation tests were normal; her d-dimers were 2060. An ultrasound examination of the urinary tract demonstrated a giant mass in the vesical dome (Figure 1).

http://bit.ly/2Blzivb

Juvenile Idiopathic Arthritis—Education, Knowledge, and Patient Outcomes

Approximately 1 in 1000 children are affected by the various subtypes of juvenile idiopathic arthritis (JIA).1 As in other chronic diseases, confronting JIA involves physical, social, emotional, and psychological challenges for the child and the family.2,3

http://bit.ly/2Ty527r

Cerebral Oxygen Saturation and Negative Postoperative Behavioral Changes in Pediatric Surgery: A Prospective Observational Study

To evaluate if an intraoperative cerebral regional oxygen saturation (crSO2) decrease, less pronounced than 20% below baseline (the current threshold believed to be associated with cognitive dysfunction in adults), is associated with negative postoperative behavioral changes (NPOBC) in the pediatric population after noncardiac surgeries.

http://bit.ly/2TxAK4T

ASGE update

http://bit.ly/2WMbR7g

Focus on...

http://bit.ly/2RLh0ZW

Antithrombotic therapy and gastric EMR or endoscopic submucosal dissection: The bleeding edge?

The number and complexity of endoscopic procedures performed by gastroenterologists and surgeons have increased in parallel with the increasing number of antithrombotic agents in clinical use.1,2 The decision to stop and resume 1 or more of these antithrombotic agents in the periprocedural period is challenging, and one must consider several patient-specific and procedure-specific factors, most notably the indication for antithrombotic use and the bleeding risk associated with the procedure. Acute coronary syndrome and stroke carry high rates of morbidity and mortality and are dreaded adverse events of withholding antithrombotic agents.

http://bit.ly/2WMbQQK

Oldie but goodie? Do attending endoscopists really need their fellows?

In their retrospective study of more than 2000 colonoscopies, Bitar et al1 showed that adenoma detection rate (ADR) was not increased by the participation of fellows during colonoscopy. This finding prompted us to review our past 2 consecutive years of colonoscopy data of 2241 screening, surveillance, and diagnostic examinations (1580; 70.5% fellow-involved), inflammatory bowel disease evaluation and obstruction cases excluded. ADR, mean adenoma per colonoscopy, and examination completion rate were not different between the fellow-involved and the attending endoscopist-only groups (27.8% vs 26.1%, 0.45 ± 0.93 vs 0.44 ± 0.98 and 95.3% vs 94.6% [P = .51], respectively).

http://bit.ly/2RGfV5B

Response:

We are very grateful for the thoughtful and supportive letter from Dr Kotzev1 regarding our article2 and for the opportunity to further a dialogue on facilitating training for endoscopic submucosal dissection (ESD) in the United States.

http://bit.ly/2WM39X1

Information for readers

http://bit.ly/2RHcf3a

Endoscopic drainage of postoperative pancreatic leaks: A great idea!

Every pancreatic surgeon should read this article by this group of talented interventional gastroenterologists from 3 university centers in Germany. Why? Because all of us pancreatic surgeons (at least those of us who are honest) have observed pancreatic leaks, and these leaks can be very difficult to manage. Having been on the surgical staff at Mayo Clinic Rochester for 30 years, I have had the privilege of working in a truly multidisciplinary environment with unbelievably gifted interventional gastroenterologists (like Todd Baron, who was one of the pioneers in the late 1990s in this aggressive endoscopic management of pancreatic collections), complemented by similarly gifted interventional radiologists, who would manipulate our operatively placed, peripancreatic drains into adjacent, inappropriately or undrained, peripancreatic collections after a pancreatectomy.

http://bit.ly/2WIojFf

Reimbursement for endoscopic innovations: the final hurdle

After the introduction of the cardiomyotomy by Dr Ernst Heller in 1913 for treating achalasia, surgeons have pursued a variety of different approaches to performing the procedure: transabdominal, transthoracic, thoracoscopic, and laparoscopic. But from the outset, the essence of the operation has remained the same: a longitudinal division of the lower esophageal sphincter. When the operation evolved to a per-oral endoscopic myotomy (POEM) in 2008, it was regarded as simply another iteration of Dr Heller's operation but by a less invasive route.

http://bit.ly/2RLgX0c

Response

We thank Drs Gkolfakis, Tziatzios, and Triantafyllou1 for their interest and their thoughtful comments on our study.2 A retrospective analysis of their colonoscopy cohort yielded similar results as to the lack of difference in the adenoma detection rate (ADR) between procedures involving trainees and those performed by attendings only. We agree with their conclusion that involvement by fellows should cause no worsening in ADR. Effectively, similar ADRs attest to an adequate training environment under proper supervision by attendings.

http://bit.ly/2WFKpbD

A promising countertraction method for faster adoption of endoscopic submucosal dissection in a Western setting

The prospective randomized study from Ge et al1 provoked my strong interest. They examined the efficacy of the suture pulley countertraction method for endoscopic submucosal dissection (ESD) as used by novices for both suturing and ESD. Using an ex vivo porcine stomach model, the participants carried out each technique under the control of an ESD expert. The spectacular results showed that the mean total procedure time was significantly shorter for all participants when suture pulley ESD was performed in comparison with traditional ESD.

http://bit.ly/2RGQyAt

Editors

http://bit.ly/2WJZ7OL

Screening for esophageal squamous cell carcinoma: insight from experience with Barrett's esophagus

We read with great interest the article by Codipilly et al,1 which reviewed recent advances in screening for esophageal squamous cell carcinoma (ESCC) and its precursor, including endoscopic and nonendoscopic modalities. Mass endoscopic screening would present a cost-effective challenge and is not tenable in most high-incidence regions except in a few ultra–high-prevalence areas.2,3 Esophageal balloon cytology screening was once widely used in China but is no longer recommended because of its low accuracy in asymptomatic individuals.

http://bit.ly/2REjUiU

In upcoming issues...

http://bit.ly/2WGVtoF

Avoiding the tube: ERCP and EUS approaches to gallbladder drainage as alternatives to percutaneous cholecystostomy in patients with cholecystitis

Cholecystitis has, for all intents and purposes, not been a disease that gastroenterologists have historically been called upon to treat. The lines of demarcation were clear and well understood. Patients with cholecystitis were the purview of surgeons who would perform cholecystectomy (CCY) whenever possible. Patients who were thought to be unfit for CCY were handed off to interventional radiologists for placement of a percutaneous cholecystostomy tube (which was often placed on a long-term or permanent basis and referred to as "destination therapy").

http://bit.ly/2RGXIVi

Challenges and pitfalls of investigating duodenal cancer in patients with familial adenomatous polyposis

Duodenal carcinoma is a rare manifestation of familial adenomatous polyposis (FAP). A lifetime cumulative incidence of duodenal cancer of around 4.5% (95% confidence interval, 0.1%-8.9%) was reported by the age of 57 years in the period of 1990 to 2001.1 In the meantime, however, the improved treatment of patients with FAP in general has resulted in longer life expectancy.2 Therefore, the natural course of the disease progresses further, and patients experience more-advanced stages of duodenal polyposis.

http://bit.ly/2WJiOpW

A rule‐based method to model myocardial fiber orientation in cardiac biventricular geometries with outflow tracts

Abstract

Rule‐based methods are often used for assigning fiber orientation to cardiac anatomical models. However, existing methods have been developed using data mostly from the left ventricle. As a consequence, fiber information obtained from rule‐based methods often does not match histological data in other areas of the heart such as the right ventricle, having a negative impact in cardiac simulations beyond the left ventricle. In this work, we present a rule‐based method where fiber orientation is separately modeled in each ventricle following observations from histology. This allows to create detailed fiber orientation in specific regions such as the endocardium of the right ventricle, the interventricular septum and the outflow tracts. We also carried out electrophysiological simulations involving these structures and with different fiber configurations. In particular, we built a modelling pipeline for creating patient‐specific volumetric meshes of biventricular geometries, including the outflow tracts, and subsequently simulate the electrical wavefront propagation in outflow tract ventricular arrhythmias with different origins for the ectopic focus. The resulting simulations with the proposed rule‐based method showed a very good agreement with clinical parameters such as the 10 ms isochrone ratio in a cohort of nine patients suffering from this type of arrhythmia. The developed modelling pipeline confirms its potential for an in silico identification of the site of origin in outflow tract ventricular arrhythmias before clinical intervention.

http://bit.ly/2Bm4Jpn

Site-Directed Mutagenesis for In Vitro and In Vivo Experiments Exemplified with RNA Interactions in Escherichia Coli

Site-directed mutagenesis is a technique used to introduce specific mutations in deoxyribonucleic acid (DNA). This protocol describes how to do site-directed mutagenesis with a 2-step and 3-step polymerase chain reaction (PCR) based approach, which is applicable to any DNA fragment of interest.

http://bit.ly/2UK6UKE

Assessment of the Efficacy of An Osteopathic Treatment in Infants with Biomechanical Impairments to Suckling

Osteopathy is an emerging field of clinical research. Here we present a protocol to assess the efficacy of an osteopathic intervention coupled with lactation consultation, in infants with biomechanical issues impeding breastfeeding.

http://bit.ly/2Sb4gRb

Preparation of Graphene Liquid Cells for the Observation of Lithium-ion Battery Material

Here, we present a protocol for the fabrication and preparation of a graphene liquid cell for in situ transmission electron microscopy observation, along with a synthesis of electrode materials and electrochemical battery cell tests.

http://bit.ly/2HV2HlB

Few Teens Meet Sleep, Exercise, Screen-Time Guidelines

TUESDAY, Feb. 5, 2019 -- Few adolescents meet sleep, physical activity, and screen-time guidelines concurrently, according to a study published online Feb. 4 in JAMA Pediatrics. Gregory Knell, Ph.D., from the University of Texas Health Science...

http://bit.ly/2DWDQKt

No Increased Risk for Cancer for ART-Conceived Children

TUESDAY, Feb. 5, 2019 -- Children conceived by assisted reproductive technology (ART) do not appear to have a significantly increased cancer risk, according to a study published online Feb. 4 in Human Reproduction. Mandy Spaan, from the Netherlands...

http://bit.ly/2MPp0bi

Ethnic Differences Seen at Time of Dementia Diagnosis in U.K.

TUESDAY, Feb. 5, 2019 -- In the United Kingdom, patients from minority ethnic groups have lower cognitive scores and are younger at first diagnosis of dementia than the white U.K.-born population, according to a study published online Jan. 24 in the...

http://bit.ly/2DTeZa3.

Long-Term Opioid Use With OA Varies Across States

TUESDAY, Feb. 5, 2019 -- There is substantial variation across states in rates of long-term opioid therapy among patients with advanced osteoarthritis, according to a study published online Jan. 28 in Arthritis & Rheumatology. Rishi J. Desai,...

http://bit.ly/2MQ9And

8 Questions Helpful for Assessing IBD in Primary Care

TUESDAY, Feb. 5, 2019 -- The CalproQuest, an eight-item questionnaire, is a feasible instrument for assessing patients for inflammatory bowel disease in primary care settings, according to a study published in the February issue of the Journal of...

http://bit.ly/2DVWSQZ

Burden of Sudden Cardiac Death Higher in Black Men, Women

TUESDAY, Feb. 5, 2019 -- African-Americans have a higher burden of sudden cardiac death (SCD) than whites, especially among women, according to a study published online Feb. 4 in Circulation. Di Zhao, Ph.D., from the Johns Hopkins University...

http://bit.ly/2DUmeyL

Outcomes Good for Autologous Reconstruction After Implant Fail

TUESDAY, Feb. 5, 2019 -- Autologous breast reconstruction after failed implant-based reconstruction seems safe and is associated with improved patient outcomes, according to a study published in the February issue of Plastic and Reconstructive...

http://bit.ly/2MNYrTZ

Evidence of Therapeutic Efficacy Substantial for Cannabis Use

TUESDAY, Feb. 5, 2019 -- Most qualifying conditions for which patients are licensed to use cannabis medically have substantial or conclusive evidence of therapeutic efficacy, according to a report published in the February issue of Health...

http://bit.ly/2MPhFZ9

Compounded Topical Pain Creams No Better Than Placebo

TUESDAY, Feb. 5, 2019 -- Compounded topical pain creams are no better than placebo creams for neuropathic pain, nociceptive pain, or mixed pain, according to a study published online Feb. 5 in the Annals of Internal Medicine. Robert E. Brutcher,...

http://bit.ly/2MQ9CeP

AAP Releases 2019 Childhood Immunization Schedules

TUESDAY, Feb. 5, 2019 -- The 2019 recommended childhood and adolescent immunization schedules have been issued by the American Academy of Pediatrics and published online Feb. 5 in Pediatrics. Yvonne A. Maldonado, M.D., and colleagues from the...

http://bit.ly/2DUmfmj

Polyethyleneimine-coated Iron Oxide Nanoparticles as a Vehicle for the Delivery of Small Interfering RNA to Macrophages In Vitro and In Vivo

We describe a method of using polyethyleneimine (PEI)-coated superparamagnetic iron oxide nanoparticles for transfecting macrophages with siRNA. These nanoparticles can efficiently deliver siRNA to macrophages in vitro and in vivo and silence target gene expression.

http://bit.ly/2BlWt8y

Anatomically Realistic Neonatal Heart Model for Use in Neonatal Patient Simulators

This protocol describes a procedure for creating functional artificial neonatal heart models by utilizing a combination of magnetic resonance imaging, 3D printing, and injection molding. The purpose of these models is for integration into the next generation of neonatal patient simulators and as a tool for physiological and anatomical studies.

http://bit.ly/2TCdHGc