Yersinia Enterocolitica Sepsis in an Elderly Male With No Iron Overload: A Case Report From the Northeastern United States.

Yersinia enterocolitica (YE) is a facultative anaerobic gram-negative coccobacillus of the genus Yersinia (the most common ones are YE serogroups O:3; O:5,27; O:8; and O:9). Its incubation period is typically 1-14 days. The symptoms of YE infection include fever, abdominal pain (which may mimic appendicitis), and diarrhea (which may be bloody and can persist for several weeks). It is most commonly reported in infants and children due to cross-contamination of their feeds and pacifiers by people handling pork products, especially while cooking chitterlings. Necrotizing enterocolitis has been described in infants following YE infections. Adults who are immunocompromised or in an iron-overload state can develop sepsis with YE infection, which has a high fatality rate. Post-infectious sequelae like reactive arthritis and erythema nodosum can occur in certain HLA types. The diagnosis is made by isolating the organism from the body fluids, stool. The gastrointestinal (GI) pathogen panel by polymerase chain reaction (PCR) is helpful in making an early diagnosis. In this report, we discuss a case of an elderly male from a nursing facility who presented with abdominal pain, vomiting, GI bleeding, and sepsis. He required a brief ICU stay and pressor support. GI pathogen panel was instrumental in the early diagnosis of YE. This condition is not often reported in the Northeastern US. Using GI pathogen PCR testing will lead to the detection of more cases of YE in geographical regions where it was not considered prevalent.

Correction: Access to Electronic Personal Health Records Among Patients With Multiple Chronic Conditions: A Secondary Data Analysis.

[This corrects the article DOI: .].

Development of a Health Policy Elective for Medical Students During the COVID-19 Pandemic: A Pilot Study.

INTRODUCTION: In Central Brooklyn, Downstate Health Sciences University (DHSU) serves a diverse population that has experienced worsening rates of chronic disease and elevated rates of morbidity and mortality related to the COVID-19 pandemic. The medical community has shown an interest in addressing clinical and nonclinical disparities impacting patients' health and safety. As such, health policy knowledge is of special importance during a time of social and political unrest. Health policy and advocacy are listed in medical education guidelines, but there is a lack of standardized guidelines for implementation of a robust health policy curriculum within the rigors of clinical education. METHODS: Faculty from the Department of Family Medicine and the Department of Health Policy and Administration devised a health policy curriculum to be delivered virtually in the wake of COVID-19-related quarantine. To assess the effectiveness of the curriculum, we administered pre- and postsurveys composed of learning objectives placed on a 5-point Likert scale, at each learning session. RESULTS: The results of these surveys showed an increase in confidence in the learning objectives of each educational session. CONCLUSION: This pilot study warrants further research to fully assess the effect of a health policy curriculum on students' confidence in health policy knowledge and skills."Education is the most powerful weapon which you can use to change the world."-Nelson Mandela.

Quantification of Viral and Host Biomarkers in the Liver of Rhesus Macaques: A Longitudinal Study of Zaire Ebolavirus Strain Kikwit (EBOV/Kik).

Zaire ebolavirus (EBOV) causes Ebola virus disease (EVD), which carries a fatality rate between 25% and 90% in humans. Liver pathology is a hallmark of terminal EVD; however, little is known about temporal disease progression. We used multiplexed fluorescent immunohistochemistry and in situ hybridization in combination with whole slide imaging and image analysis (IA) to quantitatively characterize temporospatial signatures of viral and host factors as related to EBOV pathogenesis. Eighteen rhesus monkeys euthanized between 3 and 8 days post-infection, and 3 uninfected controls were enrolled in this study. Compared with semiquantitative histomorphologic ordinal scoring, quantitative IA detected subtle and progressive features of early and terminal EVD that was not feasible with routine approaches. Sinusoidal macrophages were the earliest cells to respond to infection, expressing proinflammatory cytokine interleukin 6 (IL6) mRNA, which was subsequently also observed in fibrovascular compartments. The mRNA of interferon-stimulated gene-15 (ISG-15), also known as ISG15 ubiquitin like modifier (ISG15), was observed early, with a progressive and ubiquitous hybridization signature involving mesenchymal and epithelial compartments. ISG-15 mRNA was prominent near infected cells, but not in infected cells, supporting the hypothesis that bystander cells produce a robust interferon gene response. This study contributes to our current understanding of early EVD progression and illustrates the value that digital pathology and quantitative IA serve in infectious disease research.

"I Knew I Could Make a Difference": Motivations and Barriers to Engagement in Fighting the West African Ebola Outbreak Among U.S.-Based Health Professionals.

The 2014 West African Ebola outbreak was unprecedented in scale and required significant international assistance. Many U.S.-based health professionals traveled to West Africa to participate in the response, whereas others considered participation, but ultimately decided against it. This study explores motivators, facilitators, and barriers to international health care worker mobilization. We conducted 24 semistructured in-depth interviews and one focus group discussion with clinical and nonclinical responders and nonresponders. Responders reported feeling duty-bound to help, confidence in their training, and prior experience in humanitarian response. Media coverage was perceived to create environments of stigma and misinformation. Supportive workplaces and clear leave of absence policies facilitated engagement, whereas unsupportive workplaces posed barriers. Although nonresponders were included in the study, the dynamics of nonresponse were less clear and warrant further exploration. Understanding how to support health professionals in responding to outbreak situations may improve mobilization in future public health crises.

Risk of MGUS in relatives of multiple myeloma cases by clinical and tumor characteristics.

We and others have shown increased risk of monoclonal gammopathy of undetermined significance (MGUS) in first-degree relatives of patients with multiple myeloma (MM). Whether familial risk of MGUS differs by the MM proband's age at onset, tumor or clinical characteristics is unknown. MM and smoldering MM (SMM) cases (N = 430) were recruited from the Mayo Clinic in Rochester, Minnesota between 2005-2015. First-degree relatives over age 40 provided serum samples for evaluation of MGUS (N = 1179). Age and sex specific rates of MGUS among first-degree relatives were compared to a population-based sample. Cytogenetic subtypes were classified by Fluorescence in situ hybridization. MGUS was detected in 75 first-degree relatives for an age- and sex- adjusted prevalence of 5.8% (95% CI: 4.5-7.2). Prevalence of MGUS in first-degree relatives was 2.4 fold (95% CI: 1.9-2.9) greater than expected rates. Familial risk did not differ by proband's age at diagnosis, gender, isotype, IgH translocation, or trisomy. This study confirms first-degree relatives of MM cases have a significantly higher risk of MGUS compared to the general population, regardless of age, gender, or tumor characteristics. In selected situations, such as multiple affected first-degree relatives, screening of first-degree relatives of MM cases could be considered for follow-up and prevention strategies.

Differences in Access to and Use of Electronic Personal Health Information Between Rural and Urban Residents in the United States.

PURPOSE: The increase in use of health information technologies (HIT) presents new opportunities for patient engagement and self-management. Patients in rural areas stand to benefit especially from increased access to health care tools and electronic communication with providers. We assessed the adoption of 4 HIT tools over time by rural or urban residency. METHODS: Analyses were conducted using data from 7 iterations of the National Cancer Institute's Health Information National Trends Survey (HINTS; 2003-2014). Rural/urban residency was based on the USDA's 2003 Rural-Urban Continuum Codes. Outcomes of interest included managing personal health information online; whether providers maintain electronic health records (EHRs); e-mailing health care providers; and purchasing medicine online. Bivariate analyses and logistic regression were used to assess relationships between geography and outcomes, controlling for sociodemographic characteristics. FINDINGS: In total, 6,043 (17.6%, weighted) of the 33,749 respondents across the 7 administrations of HINTS lived in rural areas. Rural participants were less likely to report regular access to Internet (OR = 0.70, 95% CI = 0.61-0.80). Rural respondents were neither more nor less likely to report that their health care providers maintained EHRs than were urban respondents; however, they had decreased odds of managing personal health information online (OR = 0.59, 95% CI = 0.40-0.78) and e-mailing health care providers (OR = 0.62, 95% CI = 0.49-0.77). CONCLUSIONS: The digital divide between rural and urban residents extends to HIT. Additional investigation is needed to determine whether the decreased use of HIT may be due to lack of Internet connectivity or awareness of these tools.

The Health Information National Trends Survey (HINTS): A Resource for Consumer Engagement and Health Communication Research.

The contemporary healthcare system can help improve health literacy outcomes in two ways: first, by nurturing the skills and motivations needed for patients to be actively engaged in their own health and healthcare decisions; and, second, by creating a prepared and proactive healthcare system that adapts to patients' capacities and needs in efficacious ways. In 2001, the National Cancer Institute launched the Health Information National Trends Survey (HINTS) as a way for researchers and planners to understand how the public is interacting with a rapidly changing health information environment. Original iterations of the HINTS national probability sampling strategies took place on a biennial basis, but in subsequent years the protocol moved to a yearly administration. This yields a rich resource of cross-sectional, national surveillance data to evaluate for trends across and within vulnerable populations. Sixteen studies are presented from the published literature to illustrate how HINTS data were used to explore constructs of direct interest to health literacy researchers. Suggestions are given for how this ongoing public surveillance mechanism can be used: (a) to provide a sentinel view of how the public is interacting with information in the environment to address their health needs; (b) to generate research questions and hypotheses for further exploration using complementary methodologies; and

Access to Electronic Personal Health Records Among Patients With Multiple Chronic Conditions: A Secondary Data Analysis.

BACKGROUND: In the United States, national incentives for offering access to electronic personal health records (ePHRs) through electronic means are geared toward creating a culture of patient engagement. One group of patients who stand to benefit from online access to ePHRs is the growing population with multiple chronic conditions (MCC). However, little is known about the current availability and use of ePHRs and patient portals among those managing MCC. OBJECTIVE: The aim was to determine the associations between number of chronic conditions and sociodemographic characteristics and usage of ePHRs, and to assess how the public's use of ePHRs varies across subpopulations, including those with MCC. METHODS: This study used data collected from the 2014 Health Information National Trends Survey (HINTS), and assessed differences in use of ePHRs between those with and without MCC (N=3497) using multiple logistic regression techniques. Variables associated with health care systems (insurance status, having a regular provider) and patient-reported self-efficacy were included in the statistical models. RESULTS: Those with MCC (n=1555) had significantly higher odds of accessing their records three or more times in the past year compared to those reporting no chronic conditions (n=1050; OR 2.46, 95% CI 1.37-4.45), but the overall percentage of those with MCC using ePHRs remained low (371 of 1529 item respondents, 25.63% weighted). No difference in odds of accessing their records was found between those reporting one chronic condition (n=892) and those reporting none (n=1050; OR 1.02, 95% CI 0.66-1.58). Significant differences in odds of accessing ePHRs were seen between income and age groups (P<.001 and P=.05, respectively), and by whether respondents had a regular provider (P=.03). CONCLUSIONS: We conclude that ePHRs provide a unique opportunity to enhance MCC patient self-management, but additional effort is needed to ensure that these patients are able to access their ePHRs. An increase in availability of patient access to their ePHRs may provide an opportunity to increase patient engagement and support self-management for all patients and especially those with MCC.

Public use of electronic personal health information: Measuring progress of the Healthy People 2020 Objectives.

Use of the internet for seeking and managing health information in the U.S., Europe, and emerging and developing nations is growing. Recent global trends indicate more interactive uses of the internet including online communication with providers. In the U.S., The Healthy People 2020 (HP2020) initiative was created by the Department of Health and Human Services to provide 10-year goals for improving the health of American citizens. Two goals of HP2020 were to increase the proportion of individuals who use the Internet to keep track of their personal health information (PHI) online and to increase the proportion of individuals who use the internet to communicate with their healthcare provider. In the present study, we use data from the seven administrations of the Health Information National Trends Survey (HINTS) to assess progress towards these goals. These data were analyzed using descriptive, bivariate, and logistic regression analytic techniques. Results of this study suggested that the HP2020 target of having 15.7% of individuals manage their PHI online by 2020 has already been exceeded (28.1%); similarly, the goal for proportion of individuals communicating with their provider using the internet (15.0%) was exceeded by 2014 (29.7%). While progress towards these goals was positive in all sociodemographic groups for both goals, differences in the rate of progress were seen by gender, race/ethnicity, income, and education, but not by age group. The rapidly increasing proportion of individuals globally who use the internet to manage their health information provides unique opportunities for patient-centered health information technology interventions.

Progress on Broadband Access to the Internet and Use of Mobile Devices in the United States.

Healthy People 2020 (HP2020) aims to improve population health outcomes through several objectives, including health communication and health information technology. We used 7 administrations of the Health Information National Trends Survey to examine HP2020 goals toward access to the Internet through broadband and mobile devices (N = 34 080). We conducted descriptive analyses and obtained predicted marginals, also known as model-adjusted risks, to estimate the association between demographic characteristics and use of mobile devices. The HP2020 target (7.7% of the US population) for accessing the Internet through a cellular network was surpassed in 2014 (59.7%), but the HP2020 target (83.2%) for broadband access fell short (63.8%). Sex and age were associated with accessing the Internet through a cellular network throughout the years (Wald F test, P <.05). The increase in the percentage of people accessing the Internet through mobile devices presents an opportunity for technology-based health interventions that should be explored.

Common medications and prostate cancer mortality: a review.

PURPOSE: Most prostate cancer patients also have comorbidities that are treated with both prescription and nonprescription medications; furthermore, many use dietary supplements. We assess their association with prognosis after prostate cancer diagnosis, and we discuss methodological challenges and clinical implications. METHODS: We reviewed high-quality observational studies investigating the association of commonly used medications and supplements with prostate cancer-specific mortality. RESULTS: There is preliminary evidence that statins and metformin use may be associated with lower risk of cancer-specific mortality after prostate cancer diagnosis; conversely, high calcium and multivitamin supplementation may be associated with increased risk. Evidence is inconclusive for nonsteroidal anti-inflammatory drugs, acetylsalicylic acid (aspirin), insulin, antihypertensives such as angiotensin-converting enzyme inhibitors and beta-blockers, digoxin, and warfarin. Common limitations of the internal validity of studies examined include unmeasured confounding and confounding by indication, competing risks, and time-related biases such as immortal time bias. The majority of studies focused on Caucasian men with specific comorbidities, while heterogeneity among patients and tumors was mostly not assessed. CONCLUSIONS: Commonly prescribed medications and over-the-counter supplements may influence prognosis among prostate cancer patients. Further well-designed pharmacoepidemiologic studies and randomized controlled trials of selected medications in appropriate patient groups are necessary before these drugs can bear new indications for prostate cancer treatment. We discuss considerations when deciding about use of these drugs in clinical practice at the present time.

ReRouting biomedical innovation: observations from a mapping of the alternative research and development (R&D) landscape.

In recent years, the world has witnessed the tragic outcomes of multiple global health crises. From Ebola to high prices to antibiotic resistance, these events highlight the fundamental constraints of the current biomedical research and development (R&D) system in responding to patient needs globally.To mitigate this lack of responsiveness, over 100 self-identified "alternative" R&D initiatives, have emerged in the past 15 years. To begin to make sense of this panoply of initiatives working to overcome the constraints of the current system, UAEM began an extensive, though not comprehensive, mapping of the alternative biomedical R&D landscape. We developed a two phase approach: (1) an investigation, via the RE:Route Mapping, of both existing and proposed initiatives that claim to offer an alternative approach to R&D, and (2) evaluation of those initiatives to determine which are in fact achieving increased access to and innovation in medicines. Through phase 1, the RE:Route Mapping, we examined 81 initiatives that claim to redress the inequity perpetuated by the current system via one of five commonly recognized mechanisms necessary for truly alternative R&D.Preliminary analysis of phase 1 provides the following conclusions: 1. No initiative presents a completely alternative model of biomedical R&D. 2. The majority of initiatives focus on developing incentives for drug discovery. 3. The majority of initiatives focus on rare diseases or diseases of the poor and marginalized. 4. There is an increasing emphasis on the use of push, pull, pool, collaboration and open mechanisms alongside the concept of delinkage in alternative R&D. 5. There is a trend towards public funding and launching of initiatives by the Global South. Given the RE:Route Mapping's inevitable limitations and the assumptions made in its methodology, it is not intended to be the final word on a constantly evolving and complex field; however, its findings are significant. The Mapping's value lies in its timely and unique insight into the importance of ongoing efforts to develop a new global framework for biomedical R&D. As we progress to phase 2, an evaluation tool for initiatives focused on identifying which approaches have truly achieved increased innovation and access for patients, we aim to demonstrate that there are a handful of initiatives which represent some, but not all, of the building blocks for a new approach to R&D.Through this mapping and our forthcoming evaluation, UAEM aims to initiate an evidence-based conversation around a truly alternative biomedical R&D model that serves people rather than profits.

The Value of Systematic Reviews in Estimating the Cost and Barriers to Translation in Tissue Engineering.

Little quantitative data exist concerning barriers that impede translation from bench to bedside. We systematically reviewed synthetic or biosynthetic polymer nerve scaffolds for peripheral nerve repair to study a defined research area that is beyond the discovery phase and has potential for clinical application. Using electronic and manual search methods, we identified published English language articles, where scaffolds were tested in preclinical animal models. A systematic review of these 416 reports estimated all costs related to the use of animals, surgery, and evaluation methods. The research studied 17 different nerves in eight animal species, with use of 65 evaluation methods at an estimated cost of $61,264,910 for the preclinical studies. A total of 127 surveys were sent to authors, of whom 12 could not be accessed electronically and 45 (39%) responded. Major causes for failure to translate included lack of a commercial partner, insufficient financial resources, a research program not involved in translation, and lack of expertise in regulatory affairs. This review emphasizes the urgent need for standardization of preclinical models and the need to establish better collaboration between laboratory investigators, clinicians, and the companies involved in commercialization. It identifies important areas for education of future investigators in the process of translation from discovery to improved health such as those funded by the National Institutes of Health Clinical and Translational Science Awards.

The role of Internet resources in clinical oncology: promises and challenges.

The Internet is a valuable tool that continues to revolutionize many aspects of our lives; however, the ability to disseminate diverse data across populations and nations presents both opportunities and challenges. Online resources are increasingly used in health care, providing wider access to information for patients, researchers, and clinicians. At the turn of the millennium, the National Cancer Institute (NCI) predicted that Internet-based technologies would create a revolution in communication for oncology professionals and patients with cancer. Herein, findings from the NCI's Health Information National Trends Survey are reviewed to give insight into how Internet trends related to oncology patients are evolving. Future trends are discussed, including examples of 'connected health' in oncology; the spread of mobile and ubiquitous access points to Internet-hosted information; the diffusion of devices, sensors, and apps; the spread of personal data sharing; and an evolution in how networks can support person-centred and family-centred care.

The association of copy number variation and percent mammographic density.

BACKGROUND: Percent mammographic density (PD) estimates the proportion of stromal, fat, and epithelial breast tissues on the mammogram image. Adjusted for age and body mass index (BMI), PD is one of the strongest risk factors for breast cancer. Inherited factors are hypothesized to explain between 30 and 60% of the variance in this trait. However, previously identified common genetic variants account for less than 6% of the variance in PD, leaving much of the genetic contribution to this trait unexplained. We performed the first study to examine whether germline copy number variation (CNV) are associated with PD. Two genome-wide association studies (GWAS) of percent density conducted on the Illumina 660W-Quad were used to identify and replicate the association between candidate CNVs and PD: the Minnesota Breast Cancer Family Study (MBCFS) and controls from the Mayo Venous Thromboembolism (Mayo VTE) Case-Control Study, with 585 and 328 women, respectively. Linear models were utilized to examine the association of each probe with PD, adjusted for age, menopausal status and BMI. Segmentation was subsequently performed on the probe-level test statistics to identify candidate CNV regions that were associated with PD. RESULTS: Sixty-one probes from five chromosomal regions [3q26.1 (2 regions), 8q24.22, 11p15.3, and 17q22] were significantly associated with PD in MBCFS (p-values <0.0001). A CNV at 3q26.1 showed the greatest evidence for association with PD; a region without any known SNPs. Conversely, the CNV at 17q22 was largely due to the association between SNPs and PD in the region. SNPs in the 8q24.22 region have been shown to be associated with risk of many cancers; however, SNPs in this region were not responsible for the observed CNV association. While we were unable to replicate the associations with PD, two of the five CNVs (3q26.1 and 11p15.3) were also observed in the Mayo VTE controls. CONCLUSIONS: CNVs may help to explain some of the variability in PD that is currently unexplained by SNPs. While we were able to replicate the existence of two CNVs across the two GWAS studies, we were unable to replicate the associations with PD. Even so, the proximity of the identified CNV regions to loci known to be associated with breast cancer risk suggests further investigation and potentially shared genetic mechanisms underlying the PD and breast cancer association.

Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients.

Here we perform the first genome-wide association study (GWAS) of multiple myeloma (MM) survival. In a meta-analysis of 306 MM patients treated at UCSF and 239 patients treated at the Mayo clinic, we find a significant association between SNPs near the gene FOPNL on chromosome 16p13 and survival (rs72773978; P=6 × 10(-10)). Patients with the minor allele are at increased risk for mortality (HR: 2.65; 95% CI: 1.94-3.58) relative to patients homozygous for the major allele. We replicate the association in the IMMEnSE cohort including 772 patients, and a University of Utah cohort including 318 patients (rs72773978 P=0.044). Using publicly available data, we find that the minor allele was associated with increased expression of FOPNL and increased expression of FOPNL was associated with higher expression of centrosomal genes and with shorter survival. Polymorphisms at the FOPNL locus are associated with survival among MM patients.

Clinical Course and Prognosis of Non-Secretory Multiple Myeloma.

OBJECTIVE: To determine the prognosis of patients with non-secretory myeloma. Methods: We studied 124 patients diagnosed with multiple myeloma who had no monoclonal protein detected on serum and urine immunofixation at diagnosis and on all subsequent follow up testing (non-secretory myeloma). The overall survival (OS) of patients with non-secretory myeloma was compared with 7075 patients with typical myeloma seen during the same time period in whom a monoclonal protein was detected at the time of diagnosis. RESULTS: One hundred and twenty four patients met criteria for non-secretory multiple myeloma. The median follow-up was 102 months (range, 1-204 months). The median progression free survival with initial therapy was 28.6 months, and the median OS was 49.3 months. There was a significant improvement in OS since 2001; median survival 99.2 versus 43.8 months (prior to 2001) versus 99.2 months (2001-2012), P<0.001. OS was superior in patients with a normal baseline FLC ratio (n=10) compared to patients with an abnormal ratio (n=19), medians not reached in both groups. Prior to 2001, OS was similar in non-secretory myeloma (n=86) and secretory myeloma (n=4011), median 3.6 versus 3.5 years, respectively, P=0.63. However, among patients diagnosed between 2001-2012, OS was superior in non-secretory myeloma (n=36) compared to secretory myeloma (n=2942), median 8.3 versus 5.4 years, respectively, P=0.03. CONCLUSIONS: Non-secretory myeloma is an uncommon subtype of multiple myeloma. In the last decade, there has been an improvement in the survival of non-secretory myeloma, and appears superior to secretory myeloma. This article is protected by copyright. All rights reserved.

Clinical course and prognosis of non-secretory multiple myeloma.

OBJECTIVE: To determine the prognosis of patients with non-secretory myeloma. METHODS: We studied 124 patients diagnosed with multiple myeloma who had no monoclonal protein detected on serum and urine immunofixation at diagnosis and on all subsequent follow-up testing (non-secretory myeloma). The overall survival (OS) of patients with non-secretory myeloma was compared with 6953 patients with typical myeloma seen during the same time period in whom a monoclonal protein was detected at the time of diagnosis. RESULTS: One hundred and twenty-four patients met criteria for non-secretory multiple myeloma. The median follow-up was 102 months (range, 1-204 months). The median progression-free survival with initial therapy was 28.6 months, and the median OS was 49.3 months. There was a significant improvement in OS since 2001; median survival 43.8 months (prior to 2001) vs. 99.2 months (2001-2012), P < 0.001. OS was superior in patients with a normal baseline FLC ratio (n = 10) compared to patients with an abnormal ratio (n = 19), medians not reached in both groups. Prior to 2001, OS was similar in non-secretory myeloma (n = 86) and secretory myeloma (n = 4011), median 3.6 vs. 3.5 yr, respectively, P = 0.63. However, among patients diagnosed between 2001 and 2012, OS was superior in non-secretory myeloma (n = 36) compared to secretory myeloma (n = 2942), median 8.3 vs. 5.4 yr, respectively, P = 0.03. CONCLUSIONS: Non-secretory myeloma is an uncommon subtype of multiple myeloma. In the last decade, there has been an improvement in the survival of non-secretory myeloma and appears superior to secretory myeloma.