Accelerated aging mediates the associations of unhealthy lifestyles with cardiovascular disease, cancer, and mortality.

BACKGROUND: With two well-validated aging measures capturing mortality and morbidity risk, this study examined whether and to what extent aging mediates the associations of unhealthy lifestyles with adverse health outcomes. METHODS: Data were from 405,944 adults (40-69 years) from UK Biobank (UKB) and 9972 adults (20-84 years) from the US National Health and Nutrition Examination Survey (NHANES). An unhealthy lifestyles score (range: 0-5) was constructed based on five factors (smoking, drinking, physical inactivity, unhealthy body mass index, and unhealthy diet). Two aging measures, Phenotypic Age Acceleration (PhenoAgeAccel) and Biological Age Acceleration (BioAgeAccel) were calculated using nine and seven blood biomarkers, respectively, with a higher value indicating the acceleration of aging. The outcomes included incident cardiovascular disease (CVD), incident cancer, and all-cause mortality in UKB; CVD mortality, cancer mortality, and all-cause mortality in NHANES. A general linear regression model, Cox proportional hazards model, and formal mediation analysis were performed. RESULTS: The unhealthy lifestyles score was positively associated with PhenoAgeAccel (UKB: ß = 0.741; NHANES: ß = 0.874, all p < 0.001). We further confirmed the respective associations of PhenoAgeAccel and unhealthy lifestyles with the outcomes in UKB and NHANES. The mediation proportion of PhenoAgeAccel in associations of unhealthy lifestyles with incident CVD, incident cancer, and all-cause mortality were 20.0%, 17.8%, and 26.6% (all p < 0.001) in UKB, respectively. Similar results were found in NHANES. The findings were robust when using another aging measure-BioAgeAccel. CONCLUSIONS: Accelerated aging partially mediated the associations of lifestyles with CVD, cancer, and mortality in UK and US populations. The findings reveal a novel pathway and the potential of geroprotective programs in mitigating health inequality in late life beyond lifestyle interventions.

Associations between exposure to adverse childhood experiences and biological aging: Evidence from the Canadian Longitudinal Study on Aging.

People exposed to adverse childhood experiences (ACEs) suffer from an increased risk of chronic disease and shorter lifespan. These individuals also tend to exhibit accelerated reproductive development and show signs of advanced cellular aging as early as childhood. These observations suggest that ACEs may accelerate biological processes of aging through direct or indirect mechanisms; however, few population-based studies have data to test this hypothesis. We analysed ACEs and biological aging data from the Canadian Longitudinal Study on Aging (CLSA; n = 23,354 adults aged 45-85) and used the BioAge R package to compute three indices of biological aging from blood-chemistry and organ-function data: Klemera-Doubal method (KDM) biological age, phenotypic age (PA), and homeostatic dysregulation (HD). Adults with ACEs tended to be biologically older than those with no ACEs, although the observed effect-sizes were small (Cohen's d<0.15), with the exception of neglect (d=0.35 for KDM and PA). Associations were similar for men and women and tended to be smaller for older as compared to midlife participants. Subtypes of ACEs perceived as being more severe (e.g., being pushed or kicked, experiencing forced sexual activity, witnessing physical violence) and more frequent and diverse exposures were associated with relatively larger effect-sizes. These findings support the hypothesis that ACEs contribute to accelerated biological aging, although replication is needed in studies with access to prospective records of ACEs and cellular-level measurements of biological aging. Furthermore, future work to better understand the degree to which associations between ACEs and biological aging are moderated by specific life-course pathways, and mediated by lifestyle and socioeconomic factors is warranted.

Impact of international research fellows in neurosurgery: results from a single academic center.

OBJECTIVE: International research fellows have been historically involved in academic neurosurgery in the United States (US). To date, the contribution of international research fellows has been underreported. Herein, the authors aimed to quantify the academic output of international research fellows in the Department of Neurosurgery at The Johns Hopkins University School of Medicine. METHODS: Research fellows with Doctor of Medicine (MD), Doctor of Philosophy (PhD), or MD/PhD degrees from a non-US institution who worked in the Hopkins Department of Neurosurgery for at least 6 months over the past decade (2010-2020) were included in this study. Publications produced during fellowship, number of citations, and journal impact factors (IFs) were analyzed using ANOVA. A survey was sent to collect information on personal background, demographics, and academic activities. RESULTS: Sixty-four international research fellows were included, with 42 (65.6%) having MD degrees, 17 (26.6%) having PhD degrees, and 5 (7.8%) having MD/PhD degrees. During an average 27.9 months of fellowship, 460 publications were produced in 136 unique journals, with 8628 citations and a cumulative journal IF of 1665.73. There was no significant difference in total number of publications, first-author publications, and total citations per person among the different degree holders. Persons holding MD/PhDs had a higher number of citations per publication per person (p = 0.027), whereas those with MDs had higher total IFs per person (p = 0.048). Among the 43 (67.2%) survey responders, 34 (79.1%) had nonimmigrant visas at the start of the fellowship, 16 (37.2%) were self-paid or funded by their country of origin, and 35 (81.4%) had mentored at least one US medical student, nonmedical graduate student, or undergraduate student. CONCLUSIONS: International research fellows at the authors' institution have contributed significantly to academic neurosurgery. Although they have faced major challenges like maintaining nonimmigrant visas, negotiating cultural/language differences, and managing self-sustainability, their scientific productivity has been substantial. Additionally, the majority of fellows have provided reciprocal mentorship to US students.

Predictors of Academic Neurosurgical Career Trajectory among International Medical Graduates Training Within the United States.

BACKGROUND: Within the literature, there has been limited research tracking the career trajectories of international medical graduates (IMGs) following residency training. OBJECTIVE: To compare the characteristics of IMG and US medical school graduate (USMG) neurosurgeons holding academic positions in the United States and also analyze factors that influence IMG career trajectories following US-based residency training. METHODS: We collected data on 243 IMGs and 2506 USMGs who graduated from Accreditation Council for Graduate Medical Education (ACGME)-accredited neurosurgery residency programs. We assessed for significant differences between cohorts, and a logistic regression model was used for the outcome of academic career trajectory. RESULTS: Among the 2749 neurosurgeons in our study, IMGs were more likely to pursue academic neurosurgery careers relative to USMGs (59.7% vs 51.1%; P = .011) and were also more likely to complete a research fellowship before beginning residency (odds ratio [OR] = 9.19; P < .0001). Among current US academic neurosurgeons, USMGs had significantly higher pre-residency h-indices relative to IMGs (1.23 vs 1.01; P < .0001) with no significant differences between cohorts when comparing h-indices during (USMG = 5.02, IMG = 4.80; P = .67) or after (USMG = 14.05, IMG = 13.90; P = .72) residency. Completion of a post-residency clinical fellowship was the only factor independently associated with an academic career trajectory among IMGs (OR = 1.73, P = .046). CONCLUSION: Our study suggests that while IMGs begin their US residency training with different research backgrounds and achievements relative to USMG counterparts, they attain similar levels of academic productivity following residency. Furthermore, IMGs are more likely to pursue academic careers relative to USMGs. Our work may be useful for better understanding IMG career trajectories following US-based neurosurgery residency training.

Characteristics of State Policies Impact Health Care Delivery: An Analysis of Mammographic Dense Breast Notification and Insurance Legislation.

BACKGROUND: Increased breast tissue density may mask cancer and thus decrease the diagnostic sensitivity of mammography. A patient group advocacy led to the implementation of laws to increase the awareness of breast tissue density and to improve access to supplemental imaging in many states. Given limited evidence about best practices, variation exists in several characteristics of adopted policies. OBJECTIVE: To identify which characteristics of state-level policies with regard to dense breast tissue were associated with increased use of downstream breast ultrasound. RESEARCH DESIGN: This was a retrospective series of monthly cross-sections of screening mammography procedures before and after implementation of laws. SUBJECTS: A sample of 13,481,554 screening mammography procedures extracted from the MarketScan Research database performed between 2007 and 2014 on privately insured women aged 40-64 years that resided in a state that had implemented relevant legislation during that period. MEASURES: The outcome was an indicator of whether breast ultrasound imaging followed a screening mammography procedure within 30 days. The main independent variables were policy characteristics indicators. RESULTS: Notification of patients about issues surrounding increased breast density was associated with increased follow-up by ultrasound by 1.02 percentage points (P=0.016). Some policy characteristics such as the explicit suggestion of supplemental imaging or mandated coverage of supplemental imaging by health insurance augmented that effect. Other policy characteristics moderated the effect. CONCLUSIONS: The heterogeneous effect of state legislation with regard to dense breast tissue on screening mammography follow-up by ultrasound may be explained by specific and unique characteristics of the approaches taken by a variety of states.

The Many Roads toward Achieving Health Equity.

This special issue of the Journal is devoted to understanding the many roads that lead toward achieving health equity. The eleven articles in the issue portray an America that is struggling with the clash between its historical ideal of pursuing equality for all and its ambivalence toward achieving equity in all social domains, especially health. Organized in five sections, the issue contains articles that examine and analyze: the role of civil rights law and the courts in shaping health equity; the political discourse that has framed our understanding of health equity; health policies that affect health equity, such as the Medicaid program, as well as related strategies that might help to improve equity, such as the use of mobile technologies to empower individuals; immigration policies and practices that impact health equity in marginalized populations; and commentaries in the final section that explore how the Affordable Care Act has addressed health equity, how repeal of the law would jeopardize equity gains, and how the political discourse and culture of the Trump administration could adversely affect health equity.

A multicentre randomised controlled trial of Transfusion Indication Threshold Reduction on transfusion rates, morbidity and health-care resource use following cardiac surgery (TITRe2).

BACKGROUND: Uncertainty about optimal red blood cell transfusion thresholds in cardiac surgery is reflected in widely varying transfusion rates between surgeons and cardiac centres. OBJECTIVE: To test the hypothesis that a restrictive compared with a liberal threshold for red blood cell transfusion after cardiac surgery reduces post-operative morbidity and health-care costs. DESIGN: Multicentre, parallel randomised controlled trial and within-trial cost-utility analysis from a UK NHS and Personal Social Services perspective. We could not blind health-care staff but tried to blind participants. Random allocations were generated by computer and minimised by centre and operation. SETTING: Seventeen specialist cardiac surgery centres in UK NHS hospitals. PARTICIPANTS: Patients aged > 16 years undergoing non-emergency cardiac surgery with post-operative haemoglobin < 9 g/dl. Exclusion criteria were: unwilling to have transfusion owing to beliefs; platelet, red blood cell or clotting disorder; ongoing or recurrent sepsis; and critical limb ischaemia. INTERVENTIONS: Participants in the liberal group were eligible for transfusion immediately after randomisation (post-operative haemoglobin < 9 g/dl); participants in the restrictive group were eligible for transfusion if their post-operative haemoglobin fell to < 7.5 g/dl during the index hospital stay. MAIN OUTCOME MEASURES: The primary outcome was a composite outcome of any serious infectious (sepsis or wound infection) or ischaemic event (permanent stroke, myocardial infarction, gut infarction or acute kidney injury) during the 3 months after randomisation. Events were verified or adjudicated by blinded personnel. Secondary outcomes included blood products transfused; infectious events; ischaemic events; quality of life (European Quality of Life-5 Dimensions); duration of intensive care or high-dependency unit stay; duration of hospital stay; significant pulmonary morbidity; all-cause mortality; resource use, costs and cost-effectiveness. RESULTS: We randomised 2007 participants between 15 July 2009 and 18 February 2013; four withdrew, leaving 1000 and 1003 in the restrictive and liberal groups, respectively. Transfusion rates after randomisation were 53.4% (534/1000) and 92.2% (925/1003). The primary outcome occurred in 35.1% (331/944) and 33.0% (317/962) of participants in the restrictive and liberal groups [odds ratio (OR) 1.11, 95% confidence interval (CI) 0.91 to 1.34; p = 0.30], respectively. There were no subgroup effects for the primary outcome, although some sensitivity analyses substantially altered the estimated OR. There were no differences for secondary clinical outcomes except for mortality, with more deaths in the restrictive group (4.2%, 42/1000 vs. 2.6%, 26/1003; hazard ratio 1.64, 95% CI 1.00 to 2.67; p = 0.045). Serious post-operative complications excluding primary outcome events occurred in 35.7% (354/991) and 34.2% (339/991) of participants in the restrictive and liberal groups, respectively. The total cost per participant from surgery to 3 months postoperatively differed little by group, just £182 less (standard error £488) in the restrictive group, largely owing to the difference in red blood cells cost. In the base-case cost-effectiveness results, the point estimate suggested that the restrictive threshold was cost-effective; however, this result was very uncertain partly owing to the negligible difference in quality-adjusted life-years gained. CONCLUSIONS: A restrictive transfusion threshold is not superior to a liberal threshold after cardiac surgery. This finding supports restrictive transfusion due to reduced consumption and costs of red blood cells. However, secondary findings create uncertainty about recommending restrictive transfusion and prompt a new hypothesis that liberal transfusion may be superior after cardiac surgery. Reanalyses of existing trial datasets, excluding all participants who did not breach the liberal threshold, followed by a meta-analysis of the reanalysed results are the most obvious research steps to address the new hypothesis about the possible harm of red blood cell transfusion. TRIAL REGISTRATION: Current Controlled Trials ISRCTN70923932. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 60. See the NIHR Journals Library website for further project information.

Advanced Imaging Utilization Trends in Privately Insured Patients From 2007 to 2013.

OBJECTIVE: The aim of the study was to investigate whether the increase in utilization of advanced diagnostic imaging for privately insured patients in 2011 was the beginning of a new trend in imaging utilization growth, or an isolated deviation from the declining trend that began in 2008. METHODS: We extracted outpatient and inpatient CT, diagnostic ultrasound, MRI, and PET procedures from databases, for the years 2007 to 2013. This study extended previous work, covering 2012 to 2013, using the same methodology. For every year of the study period, we calculated the following: number of procedures per person-year covered by private health insurance; proportion of office and emergency visits that resulted in an imaging session; average payments per procedure; and total payments per person-year covered by private health insurance. RESULTS: Outpatient utilization of CT and PET decreased in both 2012 and 2013; outpatient utilization of MRI mildly increased in 2012, but then decreased in 2013. Outpatient utilization of diagnostic ultrasound showed a very different pattern, increasing throughout the study period. Inpatient utilization of all imaging modalities except PET decreased in both 2012 and 2013. Adjusted payments for all imaging modalities increased in 2012, and then dropped substantially in 2013, except the adjusted payments for diagnostic ultrasound that increased in 2013 again. CONCLUSIONS: The trend of increasing utilization of advanced diagnostic imaging seems to be over for some, but not all, imaging modalities. A combination of policy (eg, breast density notification laws), technologic advancement, and wider access seems to be responsible for at least part of an increasing utilization of diagnostic ultrasound.

Advanced diagnostic imaging in privately insured patients: recent trends in utilization and payments.

Recent studies have reported that the rate of growth in utilization of noninvasive diagnostic imaging has slowed, with a concomitant reduction in total payments to providers in the Medicare Part B fee-for-service population. Utilization and payment growth trends in commercially insured populations, however, are not as well understood. We used the Truven Health Analytics MarketScan® Commercial Claims and Encounters database containing more than 29 million individuals to investigate commercially insured population trends in utilization of and payments for CT, MRI, PET, and ultrasound procedures in the years 2007-2011. We found that imaging use--after a brief downturn in 2010--rose again in 2011, coupled with substantial increases in adjusted payments for all four imaging modalities, raising concerns about future efforts to stem growth in imaging use and associated spending.

Chronic cerebrospinal venous insufficiency: masked multimodal imaging assessment.

BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) was implicated in the pathophysiology of multiple sclerosis (MS). OBJECTIVE: We evaluated neurosonography (NS), magnetic resonance venography (MRV), and transluminal venography (TLV) in subsets of MS patients drawn from a single-center, prospective, case-control study of 206 MS and 70 non-MS volunteers. METHODS: As previously reported, findings on high-resolution B-mode NS imaging with color and spectral Doppler of the extracranial and intracranial venous drainage consistent with CCSVI were similar among MS and non-MS volunteers (3.88% vs 7.14%; p = 0.266). Ninety-nine MS participants consented to intravascular contrast-enhanced 3D MRV to assess their major systemic and intracranial venous circulation, and 40 advanced to TLV that included pressure measurements of the superior vena cava, internal jugular, brachiocephalic, and azygous veins. RESULTS: NS findings and MRV patterns were discrepant for 26/98 evaluable subjects, including four with abnormal findings on NS that had normal venous anatomy by MRV. In no instance were TLV pressure gradients indicative of clinically significant functional stenosis encountered. The three imaging approaches provided generally consistent data with discrepancies referable to inherent technique properties. CONCLUSIONS: Our findings lend no support for altered venous outflow dynamics as common among MS patients, nor do they likely contribute to the disease process.

An agenda for children for the 113th Congress: recommendations from the pediatric academic societies.

The 113th Congress of the United States begins in January 2013. With each new Congress, there are many changes, not only in the faces of the newly elected, but also in the membership of committees and the staff serving the members. As agendas for the session are set, there is a resurgence of conflicting priorities. In the past, when these conflicts were resolved, children were rarely at the top of the list. Given the numerous pressing national issues, both domestic and foreign, the same trend will likely occur.

Social networks--the future for health care delivery.

With the rapid growth of online social networking for health, health care systems are experiencing an inescapable increase in complexity. This is not necessarily a drawback; self-organising, adaptive networks could become central to future health care delivery. This paper considers whether social networks composed of patients and their social circles can compete with, or complement, professional networks in assembling health-related information of value for improving health and health care. Using the framework of analysis of a two-sided network--patients and providers--with multiple platforms for interaction, we argue that the structure and dynamics of such a network has implications for future health care. Patients are using social networking to access and contribute health information. Among those living with chronic illness and disability and engaging with social networks, there is considerable expertise in assessing, combining and exploiting information. Social networking is providing a new landscape for patients to assemble health information, relatively free from the constraints of traditional health care. However, health information from social networks currently complements traditional sources rather than substituting for them. Networking among health care provider organisations is enabling greater exploitation of health information for health care planning. The platforms of interaction are also changing. Patient-doctor encounters are now more permeable to influence from social networks and professional networks. Diffuse and temporary platforms of interaction enable discourse between patients and professionals, and include platforms controlled by patients. We argue that social networking has the potential to change patterns of health inequalities and access to health care, alter the stability of health care provision and lead to a reformulation of the role of health professionals. Further research is needed to understand how network structure combined with its dynamics will affect the flow of information and potentially the allocation of health care resources.

The debate over health care rationing: Déjà vu all over again?

Health care rationing has been a source of contentious debate in the United States for nearly 30 years. Because rationing is bewildering to many Americans, persistent myths about "death panels" and critical health care decisions to be made by faceless bureaucrats abound, instilling fear about health care reform and cost containment measures aimed at slowing spending growth. This paper retrospectively reviews the policy literature on health care rationing over the past quarter century, examines alternative definitions and classification schemes, traces the evolution of the debate, and explores ways in which rationing may be made more rational, transparent, and equitable in the future allocation of scarce health care resources.

Modified metabolic syndrome criteria for identification of patients at risk of developing diabetes and coronary heart diseases: longitudinal assessment via electronic health records.

BACKGROUND: Metabolic syndrome has been shown to predict type 2 diabetes mellitus and cardiovascular events in well-studied cohorts, but lack of appropriate measures in real-life populations has limited its use in clinical settings. We developed and tested an algorithm to identify patients at risk for future diabetes or coronary heart disease (CHD) events using electronic health records (EHRs) at the Centre Hospitalier Universitaire de Sherbrooke (CHUS). METHODS: Patients older than 18 years who had at least 1 visit (outpatient or inpatient) at the CHUS in 2002 or 2003 were included. We excluded patients with diabetes or CHD at baseline. Patients with at least 3 relevant measurements were classified as no metabolic syndrome (zero criteria met), at-risk for metabolic syndrome (1-2 criteria met), or having metabolic syndrome (≥ 3 criteria met). Incidence of diabetes and CHD were assessed through 2008. RESULTS: Data from 31,823 patients were included at baseline: 2997 (9.4%) were classified as having metabolic syndrome, while 18,686 (59%) were classified as at risk for metabolic syndrome. During the 5-year follow-up, having metabolic syndrome was associated with a 20.0% risk of developing diabetes (age- and sex-adjusted odds ratio = 5.12 [95% confidence interval, 4.57-5.74]; P < 0.0001) and a 14.7% CHD event incidence (age- and sex-adjusted odds ratio = 1.83 [95% confidence interval, 1.62-2.07]; P < 0.0001). CONCLUSIONS: An algorithm based on clinically available EHRs could identify patients at high cardiometabolic risk of future diabetes and CHD in the population receiving care at the CHUS.