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

[This corrects the article DOI: .].

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.

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.

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.

Rituximab for non-Hodgkin's lymphoma: a story of rapid success in translation.

Translational stories range from straightforward to complex. In this commentary, the story of the rapid and successful translation of rituximab therapy for the treatment of non-Hodgkin's lymphoma (NHL) is examined. Development of this monoclonal antibody therapy began in the late 1980s. In 1994, rituximab received its first approval for the treatment of NHL by the United States Food and Drug Administration (FDA). Rituximab has since been approved for additional indications and has transformed medical practice. However, the social and political implications of these rapid successes are only beginning to become clear. In this commentary, key events in the rapid translation of rituximab from the bench to bedside are highlighted and placed into this historical framework. To accomplish this, the story of rituximab is divided into the following six topics, which we believe to be widely applicable to case studies of translation: (1) underlying disease, (2) key basic science, (3) key clinical studies in translation, (4) FDA approval process, (5) changes to medical practice, and (6) the social and political influences on translation.

Pathways of translation: deep brain stimulation.

Electrical stimulation of the brain has a 2000 year history. Deep brain stimulation (DBS), one form of neurostimulation, is a functional neurosurgical approach in which a high-frequency electrical current stimulates targeted brain structures for therapeutic benefit. It is an effective treatment for certain neuropathologic movement disorders and an emerging therapy for psychiatric conditions and epilepsy. Its translational journey did not follow the typical bench-to-bedside path, but rather reversed the process. The shift from ancient and medieval folkloric remedy to accepted medical practice began with independent discoveries about electricity during the 19th century and was fostered by technological advances of the 20th. In this paper, we review that journey and discuss how the quest to expand its applications and improve outcomes is taking DBS from the bedside back to the bench.

Responsiveness of cytogenetically discrete human myeloma cell lines to lenalidomide: lack of correlation with cereblon and interferon regulatory factor 4 expression levels.

The introduction of novel immunomodulatory drugs (IMiDs) has dramatically improved the survival of patients with multiple myeloma (MM). While it has been shown that patients with specific cytogenetic subtypes, namely t(4;14), have the best outcomes when treated with bortezomib-based regimens, the relationship between cytogenetic subtypes and response to IMiDs remains unclear. Using DNA synthesis assays, we investigated the relationship between cytogenetic subtype and lenalidomide response in a representative panel of human myeloma cell lines (HMCLs). We examined HMCL protein expression levels of the lenalidomide target cereblon (CRBN) and its downstream target interferon regulatory factor-4 (IRF4), which have previously been shown to be predictive of lenalidomide response in HMCLs. Our results reveal that lenalidomide response did not correlate with specific cytogenetic translocations. There were distinct groups of lenalidomide-responsive and non-responsive HMCLs, as defined by inhibition of cellular proliferation; notably, all of the hyperdiploid HMCLs fell into the latter category. Repeated dosing of lenalidomide significantly lowered the IC50 of the responsive HMCL ALMC-1 (IC50 = 2.6 µm vs. 0.005 µm, P < 0.0001), but did not have an effect on the IC50 of the non-responsive DP-6 HMCL (P > 0.05). Moreover, no association was found between lenalidomide responsiveness and CRBN and IRF4 expression. Our data indicate that lenalidomide sensitivity is independent of cytogenetic subtype in HMCLs. While CRBN and IRF4 have been shown to be associated with response to lenalidomide in patients, these findings do not translate back to HMCLs, which could be attributable to factors present in the bone marrow microenvironment.

Differences in the distribution of cytogenetic subtypes between multiple myeloma patients with and without a family history of monoclonal gammopathy and multiple myeloma.

We previously reported an increased risk of monoclonal gammopathy of undetermined significance (MGUS) in first-degree relatives of MGUS and multiple myeloma patients. Here, we examine whether primary cytogenetic categories of myeloma differ between patients with and without a family history of MGUS or myeloma. We studied 201 myeloma patients with available data on family history and molecular cytogenetic classification. Myeloma with trisomies was more common in probands who had an affected first-degree relative with MGUS or myeloma compared with those without a family history (46.9% vs. 33.5%, P = 0.125); however, the difference was not statistically significant. Additional studies on the cytogenetic types of myeloma associated with familial tendency are needed.

Increased prevalence of light chain monoclonal gammopathy of undetermined significance (LC-MGUS) in first-degree relatives of individuals with multiple myeloma.

Previously, we reported increased risk of heavy-chain (HC) monoclonal gammopathy of undetermined significance (MGUS) among first-degree (1°) relatives of multiple myeloma (MM) or HC-MGUS probands. This study investigated whether there was comparable risk for light-chain (LC) MGUS among 911 relatives of the same HC-MGUS/MM probands versus a reference population of 21 463. Seventeen 1° relatives had LC-MGUS (adjusted prevalence = 1·7%, 95% CI = 0·9­2·6%). There was increased risk of LC-MGUS in relatives of MM probands (RR = 3·4, 95% CI = 2·0­5·5). We saw no increased risk in relatives of HC-MGUS probands. We conclude that the prevalence of LC-MGUS is significantly higher among 1° relatives of MM probands compared to the reference population.

Familial monoclonal gammopathy of undetermined significance and multiple myeloma: epidemiology, risk factors, and biological characteristics.

Monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma (MM), is one of the most common premalignant conditions in the general population. The cause of MGUS is largely unknown. Recent studies show that there is an increased prevalence of MGUS in blood relatives of persons with lymphoproliferative and plasma cell proliferative disorders, suggesting presence of shared underlying genetic influences. In the past few years, additional studies have examined risk factors and biologic characteristics that may contribute to the increased prevalence of MGUS among relatives of probands with MGUS, MM, and other blood malignancies. This article reviews the known epidemiology and risk factors for familial MGUS and myeloma, the risk of lymphoproliferative disorders and other malignancies among blood-relatives of patients with MGUS and MM, and discusses future directions for research.