Novel modes of MPL activation in triple-negative myeloproliferative neoplasms.

The identification of a somatic mutation associated with myeloid malignancy is of diagnostic importance in myeloproliferative neoplasms (MPNs). Individuals with no mutation detected in common screening tests for variants in JAK2, CALR, and MPL are described as 'triple-negative' and pose a diagnostic challenge if there is no other evidence of a clonal disorder. To identify potential drivers that might explain the clinical phenotype, we used an extended sequencing panel to characterise a cohort of 44 previously diagnosed triple-negative MPN patients for canonical mutations in JAK2, MPL and CALR at low variant allele frequency (found in 4/44 patients), less common variants in the JAK-STAT signalling pathway (12 patients), or other variants in recurrently mutated genes from myeloid malignancies (18 patients), including hotspot variants of potential clinical relevance in eight patients.

Factors Impacting the Decision of an Individual With Lynch Syndrome to Terminate a Health Care Provider Relationship.

Lynch syndrome (LS) is a genetic cancer syndrome that puts affected individuals at a significantly higher risk of developing multiple cancers. Participants (n = 57) were recruited through social media. Data were collected through online surveys and phone interviews; the interview data (n = 55) were analyzed to identify provider terminations and the factors that motivated these decisions.

Targeted gene panels identify a high frequency of pathogenic germline variants in patients diagnosed with a hematological malignancy and at least one other independent cancer.

The majority of studies assessing the contribution of pathogenic germline variants (PGVs) to cancer predisposition have focused on patients with single cancers. We analyzed 45 known cancer predisposition genes (CPGs) in germline samples of 202 patients with hematological malignancies (HMs) plus one or more other independent cancer managed at major tertiary medical centers on two different continents. This included 120 patients with therapy-related myeloid neoplasms (t-MNs), where the HM occurred after cytotoxic treatment for a first malignancy, and 82 patients with multiple cancers in which the HM was not preceded by cytotoxic therapy (MC-HM).

Data models, representation and adequacy-for-purpose.

We critically engage two traditional views of scientific data and outline a novel philosophical view that we call the . On the PR view, data are representations that are the product of a process of inquiry, and they should be evaluated in terms of their adequacy or fitness for particular purposes. Some important implications of the PR view for data assessment, related to misrepresentation, context-sensitivity, and complementary use, are highlighted.

Medication management in dialysis: Barriers and strategies.

People with end-stage kidney disease (ESKD) who require chronic dialysis are often reliant on complicated medication regimens to manage their health conditions. Due to the complexities of the advanced kidney disease, underlying comorbidities, and special instructions, medication regimens for patients on dialysis put patients at high risk for medication therapy problems related to safety, effectiveness, appropriateness, and adherence. This article explores the factors that affect optimal medication use for people on dialysis, including the broader drug use system, and offers recommendations around medication reconciliation, medication review, deprescribing, and considering social determinants of health to improve medication management among patients with ESKD.

Assessment of literacy and numeracy skills related to medication labels in patients on chronic in-center hemodialysis.

Objectives: Patients on hemodialysis have complicated medication regimens requiring the ability to accurately interpret medication information. Literacy and numeracy skills have been shown to differ by the types of materials provided to patients. The aims of this study were to determine prescription and over-the-counter medication label understanding and to assess the prevalence of low health literacy regarding medication labeling among in-center hemodialysis patients.

For Women, Lynch Syndrome Is About More than Colon Cancer.

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, has historically been characterized by a predisposition to colorectal cancer; however, for women with Lynch syndrome, the risks for gynecologic cancers pose an equal or greater risk than colorectal cancer. In addition, the gynecologic cancer is often the first cancer that presents in these patients. Also of importance to women with Lynch syndrome is the efficacy of gynecologic cancer screening being significantly lower than colorectal cancer screening, leading to inconsistency in provider recommendations for gynecologic screening and surveillance.

The mutational burden of therapy-related myeloid neoplasms is similar to primary myelodysplastic syndrome but has a distinctive distribution.

Therapy-related myeloid neoplasms (T-MN) are poorly characterized secondary hematological malignancies following chemotherapy/radiotherapy exposure. We compared the clinical and mutational characteristics of T-MN (n = 129) and primary myelodysplastic syndrome (P-MDS, n = 108) patients. Although the somatic mutation frequency was similar between T-MN and P-MDS patients (93% in both groups), the pattern was distinct.

Health and lifestyle behaviors in colorectal cancer survivors with and without Lynch syndrome.

Lynch syndrome (LS), a hereditary cancer syndrome, accounts for approximately 3% of colorectal cancers (CRC). Positive health behaviors and surveillance are preventive strategies, but research on whether recommended behavioral guidelines are followed by individuals with LS is limited. Additional health education and promotion could be beneficial to the improved survivorship of CRC survivors.

mutations are recurrently acquired during chronic myeloid leukemia progression and interfere with myeloid differentiation pathways.

Despite the advent of tyrosine kinase inhibitors, a proportion of chronic myeloid leukemia patients in chronic phase fail to respond to imatinib or to second-generation inhibitors and progress to blast crisis. Until now, improvements in the understanding of the molecular mechanisms responsible for chronic myeloid leukemia transformation from chronic phase to the aggressive blast crisis remain limited. Here we present a large parallel sequencing analysis of 10 blast crisis samples and of the corresponding autologous chronic phase controls that reveals, for the first time, recurrent mutations affecting the ubiquitin-conjugating enzyme E2A gene (, formerly ).

Freezing fertility or freezing false hope? A content analysis of social egg freezing in U.S. print media.

In 2012, the American Society for Reproductive Medicine (ASRM) lifted the experimental label on oocyte preservation, but cautioned against women using it to avoid age-related infertility, known as social egg freezing (SEF). In 2014, Facebook and Apple announced that they would offer SEF as a workplace benefit. Within the context of a rapidly growing market for SEF, we were interested in how these two decisions affected media discussions, given that such discourse can strongly influence public perceptions and behaviors.

Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high-risk disease.

Genomic events associated with poor outcome in chronic myeloid leukemia (CML) are poorly understood. We performed whole-exome sequencing, copy-number variation, and/or RNA sequencing for 65 patients to discover mutations at diagnosis and blast crisis (BC). Forty-six patients with chronic-phase disease with the extremes of outcome were studied at diagnosis.

"How do I say that?": Using communication principles to enhance medication therapy management instruction.

Background And Purpose: Medication therapy management (MTM) is a comprehensive, patient-centered approach to improving medication use, reducing the risk of adverse events and improving medication adherence. Given the service delivery model and required outputs of MTM services, communication skills are of utmost importance. The objectives of this study were to identify and describe communication principles and instructional practices to enhance MTM training.

and germ line variants predict response and identify CML patients with the greatest risk of imatinib failure.

Scoring systems used at diagnosis of chronic myeloid leukemia (CML), such as Sokal risk, provide important response prediction for patients treated with imatinib. However, the sensitivity and specificity of scoring systems could be enhanced for improved identification of patients with the highest risk. We aimed to identify genomic predictive biomarkers of imatinib response at diagnosis to aid selection of first-line therapy.

Experiential Education Builds Student Self-Confidence in Delivering Medication Therapy Management.

To determine the impact of advanced pharmacy practice experiences (APPE) on student self-confidence related to medication therapy management (MTM), fourth-year pharmacy students were surveyed pre/post APPE to: identify exposure to MTM learning opportunities, assess knowledge of the MTM core components, and assess self-confidence performing MTM services. An anonymous electronic questionnaire administered pre/post APPE captured demographics, factors predicted to impact student self-confidence (Grade point average (GPA), work experience, exposure to MTM learning opportunities), MTM knowledge and self-confidence conducting MTM using a 5-point Likert scale (1 = Not at all Confident; 5 = Extremely Confident). Sixty-two students (26% response rate) responded to the pre-APPE questionnaire and = 44 (18%) to the post-APPE.

Availability of information on young onset dementia for patients and carers in six European countries.

Objectives: To identify information available in six European countries (England, France, Germany, Netherlands, Portugal, Sweden) that addresses the specific needs of people with young onset dementia (YOD) and their carers, and identify gaps.

Methods: Search of websites of organisations with potential interest in dementia. Narrative synthesis and comparative analysis.

A comparison between Lynch syndrome and sporadic colorectal cancer survivors' satisfaction with their healthcare providers.

This study evaluated provider satisfaction in a sample of colorectal cancer (CRC) survivors with and without Lynch syndrome (LS). Participants were case-case-matched CRC survivors with (n = 75) or without (n = 75) LS (mean age of 55; range: 27-93). Participants completed a mailed questionnaire assessing demographics, clinical characteristics, healthcare utilization, psychosocial variables, and provider satisfaction.

The Use of Social Media to Recruit Participants With Rare Conditions: Lynch Syndrome as an Example.

Background: Social media is increasingly being used as a means of recruiting participants, particularly for investigators whose areas of interest involve rare conditions or hard-to-reach populations. However, much of the literature to date has focused on paid advertisement recruitment.

Objective: We used Lynch syndrome (LS), a rare hereditary cancer syndrome, as a model to demonstrate the successful partnership between researchers and a Web-based patient education and advocacy organization to facilitate participant recruitment.

Health-related quality of life in colorectal cancer survivors: are there differences between sporadic and hereditary patients?

Purpose: To compare health-related quality of life (HRQoL) in colorectal cancer (CRC) survivors with sporadic CRC to those with hereditary cancer, specifically Lynch syndrome (LS).

Methods: Participants completed a mailed self-administered questionnaire that assessed, among other things, demographics, clinical characteristics, and health-related quality of life. Using a case-case design, CRC survivors with LS or sporadic cancer were matched on age, sex, race/ethnicity, cancer stage, geography, and time since diagnosis.

Assessment of Macro-Level Socioeconomic Factors That Impact Waterborne Diseases: The Case of Jordan.

The Hashemite Kingdom of Jordan is an example of a country that suffers from high water scarcity. Additionally, due to the economic drivers in the country, such as phosphate and potash extraction and pharmaceutical production, the little fresh water that remains is generally polluted. The infrastructure, often antiquated in urban areas and non-existent in rural areas, also contributes to poor water conditions and to the spread of waterborne diseases.

The delicate balance of keeping it all together: Using social capital to manage multiple medications for patients on dialysis.

Objectives: Patients with end-stage kidney disease (ESKD) typically have high medication burdens with numerous medications and specialized instructions. Limited data exist regarding ESKD patient perspectives on medication management. Why can some patients self-manage? Which organizational techniques are used? This project sought to determine experiences and attitudes regarding medication management among hemodialysis patients.

Management of Zygomatic Fractures: A National Survey.

Introduction: Repair of zygomatic fractures can be classified into the early closed reduction or the more recent open reduction and rigid internal fixation (ORIF) methods. Surgical training and literature advocate ORIF, but the actual frequency of the different techniques in clinical practice is unknown. The purpose of this study was to determine the current trends in the management of zygomatic fractures among US surgeons and elucidate their influences.

BAM-matcher: a tool for rapid NGS sample matching.

Unlabelled: The standard method used by high-throughput genome sequencing facilities for detecting mislabelled samples is to use independently generated high-density SNP data to determine sample identity. However, as it has now become commonplace to have multiple samples sequenced from the same source, such as for analysis of somatic variants using matched tumour and normal samples, we can directly use the genotype information inherent in the sequence data to match samples and thus bypass the need for additional laboratory testing. Here we present BAM-matcher, a tool that can rapidly determine whether two BAM files represent samples from the same biological source by comparing their genotypes.