An electronic family health history tool to identify and manage patients at increased risk for colorectal cancer: protocol for a randomized controlled trial.

BackgroundColorectal cancer is the fourth most commonly diagnosed cancer in the United States. Approximately 3-10% of the population has an increased risk for colorectal cancer due to family history and warrants more frequent or intensive screening. Yet, < 50% of that high-risk population receives guideline-concordant care. Systematic collection of family health history and decision support may improve guideline-concordant screening for patients at increased risk of colorectal cancer. We seek to test the effectiveness of a web-based, systematic family health history collection tool and decision support platform (MeTree) to improve risk assessment and appropriate management of colorectal cancer risk among patients in the Department of Veterans Affairs primary care practices.MethodsIn this ongoing randomized controlled trial, primary care providers at the Durham Veterans Affairs Health Care System and the Madison VA Medical Center are randomized to immediate intervention or wait-list control. Veterans are eligible if assigned to enrolled providers, have an upcoming primary care appointment, and have no conditions that would place them at increased risk for colorectal cancer (such as personal history, adenomatous polyps, or inflammatory bowel disease). Those with a recent lower endoscopy (e.g. colonoscopy, sigmoidoscopy) are excluded. Immediate intervention patients put their family health history information into a web-based platform, MeTree, which provides both patient- and provider-facing decision support reports. Wait-list control patients access MeTree 12 months post-consent. The primary outcome is the risk-concordant colorectal cancer screening referral rate obtained via chart review. Secondary outcomes include patient completion of risk management recommendations (e.g. colonoscopy) and referral for genetic consultation. We will also conduct an economic analysis and an assessment of providers' experience with MeTree clinical decision support recommendations to inform future implementation efforts if the intervention is found to be effective.DiscussionThis trial will assess the feasibility and effectiveness of patient-collected family health history linked to decision support to promote risk-appropriate screening in a large healthcare system such as the Department of Veterans Affairs.Trial registrationClinicalTrials.gov, NCT02247336 . Registered on 25 September 2014

Femoroacetabular impingement and classification of the cam deformity: the reference interval in normal hips

BACKGROUND AND PURPOSE: Most patients with femoroacetabular impingement (FAI) have a cam deformity, which may be quantified by measuring the alpha angle and anterior offset ratio (AOR). Knowledge of what constitutes a "normal" alpha angle and AOR is limited. We defined the reference intervals of these measurements from normal hips in the general population. PATIENTS AND METHODS: 157 individuals from the general population were reviewed clinically and radiographically. 74 individuals with clinical evidence of hip disease or radiographic evidence of osteoarthritis (OA) were excluded, leaving a study group of 83 individuals (mean age 46 (22-69) years, 44 females) with normal hips. The alpha angles and AORs were measured from cross-table lateral radiographs taken in 15 degrees internal rotation. A validation study consisting of a cadaver study and a measurement reliability study was also performed. RESULTS: The mean alpha angle was 48 degrees in men and 47 degrees in women. The mean AOR was 0.19, the same in men and women. Thus, sexes were combined to derive 95% confidence intervals for the population mean alpha angle (46-49 degrees ) and AOR (0.18-0.20). The 95% reference interval for the alpha angle was 32-62 degrees degrees, and for the AOR it was 0.14-0.24. The validation study confirmed that these measurements were resistant to a reasonable degree of variation in positioning and that the repeatability and reproducibility of the measurements was good. INTERPRETATION: These reference intervals indicate that clinically and radiographically normal hips may have alpha angles and AORs that have previously been considered "abnormal". The thresholds provided by this study will aid classification of individuals involved in longitudinal studies of FAI and OA, and may be of use to the practicing clinician in evaluating the young adult with hip pain

Femoroacetabular impingement: normal values of the quantitative morphometric parameters in asymptomatic hips.

OBJECTIVE: To determine the means and the reference intervals of the quantitative morphometric parameters of femoroacetabular impingement (FAI) in normal hips with high-resolution computed tomography (CT). METHODS: We prospectively included 94 adult individuals who underwent CT for thoracic, abdominal or urologic pathologies. Patients with a clinical history of hip pathology and/or with osteoarthritis on CT were excluded. We calculated means and 95 % reference intervals for imaging signs of cam-type (alpha angle at 90° and 45° and femoral head-neck offset) and pincer-type impingement (acetabular version angle, lateral centre-edge angle and acetabular index). RESULTS: The 95 % reference interval limits were all far beyond the abnormal thresholds found in the literature for cam-type and to a lesser extent for pincer-type FAI. The upper limits of the reference intervals for the alpha angles (at 90°/45°) were 68°/83° (men) and 69°/84° (women), compared to thresholds from the literature (50°, 55° or 60°). Reference intervals were similar between genders for cam-type parameters, and slightly differed for pincer-type. CONCLUSION: The 95 % reference intervals of morphometric measurements of FAI in asymptomatic hips were beyond the abnormal thresholds, which was especially true for cam-type FAI. Our results suggest the need for redefining the current morphometric parameters used in the diagnosis of FAI. KEY POINTS: ? 95 % reference intervals limits of FAI morphotype were beyond currently defined thresholds. ? Reference intervals of pincer-type morphotype measurements were close to current definitions. ? Reference intervals of cam-type morphotype measurements were far beyond the current definitions. ? Current morphometric definitions of cam-type morphotype should be used with care

A research agenda to support the development and implementation of genomics-based clinical informatics tools and resources.

OBJECTIVE: The Genomic Medicine Working Group of the National Advisory Council for Human Genome Research virtually hosted its 13th genomic medicine meeting titled Developing a Clinical Genomic Informatics Research Agenda . The meeting\u27s goal was to articulate a research strategy to develop Genomics-based Clinical Informatics Tools and Resources (GCIT) to improve the detection, treatment, and reporting of genetic disorders in clinical settings. MATERIALS AND METHODS: Experts from government agencies, the private sector, and academia in genomic medicine and clinical informatics were invited to address the meeting\u27s goals. Invitees were also asked to complete a survey to assess important considerations needed to develop a genomic-based clinical informatics research strategy. RESULTS: Outcomes from the meeting included identifying short-term research needs, such as designing and implementing standards-based interfaces between laboratory information systems and electronic health records, as well as long-term projects, such as identifying and addressing barriers related to the establishment and implementation of genomic data exchange systems that, in turn, the research community could help address. DISCUSSION: Discussions centered on identifying gaps and barriers that impede the use of GCIT in genomic medicine. Emergent themes from the meeting included developing an implementation science framework, defining a value proposition for all stakeholders, fostering engagement with patients and partners to develop applications under patient control, promoting the use of relevant clinical workflows in research, and lowering related barriers to regulatory processes. Another key theme was recognizing pervasive biases in data and information systems, algorithms, access, value, and knowledge repositories and identifying ways to resolve them

Magnetic resonance arthrography of the hip: technique and spectrum of findings in younger patients

Magnetic resonance(MR) imaging is the reference imaging technique in the evaluation of hip abnormalities. However, in some pathological conditions—such as lesions of the labrum, cartilaginous lesions, femoroacetabular impingement, intra-articular foreign bodies, or in the pre-operative work-up of developmental dysplasia of the hip—intra-articular injection of a contrast medium is required to obtain a precise diagnosis. This article reviews the technical aspects, contraindications, normal appearance and potential pitfalls of MR arthrography, and illustrates the radiological appearance of commonly encountered conditions

Inside and out: the activities of senescence in cancer.

The core aspect of the senescent phenotype is a stable state of cell cycle arrest. However, this is a disguise that conceals a highly active metabolic cell state with diverse functionality. Both the cell-autonomous and the non-cell-autonomous activities of senescent cells create spatiotemporally dynamic and context-dependent tissue reactions. For example, the senescence-associated secretory phenotype (SASP) provokes not only tumour-suppressive but also tumour-promoting responses. Senescence is now increasingly considered to be an integrated and widespread component that is potentially important for tumour development, tumour suppression and the response to therapy.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nrc377

Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004

Establishing the value of genomics in medicine: the IGNITE Pragmatic Trials Network.

PURPOSE: A critical gap in the adoption of genomic medicine into medical practice is the need for the rigorous evaluation of the utility of genomic medicine interventions. METHODS: The Implementing Genomics in Practice Pragmatic Trials Network (IGNITE PTN) was formed in 2018 to measure the clinical utility and cost-effectiveness of genomic medicine interventions, to assess approaches for real-world application of genomic medicine in diverse clinical settings, and to produce generalizable knowledge on clinical trials using genomic interventions. Five clinical sites and a coordinating center evaluated trial proposals and developed working groups to enable their implementation. RESULTS: Two pragmatic clinical trials (PCTs) have been initiated, one evaluating genetic risk APOL1 variants in African Americans in the management of their hypertension, and the other to evaluate the use of pharmacogenetic testing for medications to manage acute and chronic pain as well as depression. CONCLUSION: IGNITE PTN is a network that carries out PCTs in genomic medicine; it is focused on diversity and inclusion of underrepresented minority trial participants; it uses electronic health records and clinical decision support to deliver the interventions. IGNITE PTN will develop the evidence to support (or oppose) the adoption of genomic medicine interventions by patients, providers, and payers