Adjuvanting a subunit COVID-19 vaccine to induce protective immunity.

The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD-NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD-NP in AS03 (RBD-NP-AS03), and correlated with protection from infection. RBD-NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD-NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD-NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD-NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD-NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343).

Racial, Ethnic, and Sex Differences in Eating Disorder Onset Among U.S. Military Service Members.

Bulimia nervosa (BN) and binge eating disorder (BED) are the most prevalent eating disorders (EDs) among military personnel. Although sex differences are noted in ED prevalence in military and civilian samples, mixed findings have emerged when evaluating racial and ethnic differences. The present study examined independent associations and interactions between sex, race, ethnicity, and probable BED and BN onset. The sample included 91,413 and 96,245 service members from the Millennium Cohort Study for BED and BN analyses, respectively. Up to four datapoints (from 2001-2013) were used to conduct longitudinal complementary log-log regression analyses, as participants were followed until the outcome occurred or until study completion. BN was more likely among women than men, and no sex difference emerged for BED onset. BN was more likely among Hispanic/Latinx, Multiracial, Black, and Asian/Pacific Islander (API) while BED was less likely among Black and API versus non-Hispanic/Latinx White (NHW) service members. Interactions revealed greater likelihood of BN in Hispanic/Latinx service members was driven by men. Additional efforts are needed amongst racially and ethnically diverse groups in preventing and detecting EDs in military personnel. Future intersectionality research could elucidate systemic inequities and other contributing factors to ED onset to inform prevention and treatment efforts.

Bidirectional Associations between Probable Eating Disorders and Mental Health Conditions Among Military Service Members and Veterans.

Although prior research has examined the prevalence of eating disorders (EDs) such as binge eating disorder (BED) and bulimia nervosa (BN) among military personnel, less is known regarding temporal associations between EDs and other mental health conditions. Using longitudinal data from 179,694 service members and veterans from the Millennium Cohort Study, temporal associations between EDs (BN, BED) and mental health conditions (posttraumatic stress disorder, anxiety, depression, and problem drinking) were investigated using a cross-lagged panel model approach. Results indicated consistent bidirectional associations between most mental health conditions and EDs; however, the magnitude of these cross-lagged associations varied across BN and BED. Cross-lagged effects of mental health conditions on subsequent BED were significantly stronger than BED to mental health condition cross-lagged effects. In contrast, cross-lagged effects of BN on subsequent mental health conditions were stronger than mental health conditions to BN. Preventive screening for those at risk for BN may have a stronger impact on mitigating downstream mental health conditions, while interventions among those with mental health conditions may play a greater role in eliminating maladaptive coping strategies including binge eating. Study findings underscore the importance of early detection of mental health conditions and EDs to maximize readiness among service members.

Prevalence and Risk Factors for the Development of Bulimia Nervosa and Binge Eating Disorder in a Large U.S. Military Cohort.

While bulimia nervosa (BN) and binge eating disorder (BED) are prevalent in military populations, an understanding of risk and protective factors is limited by a lack of longitudinal population-based epidemiological research. This study examined the prevalence of BN and BED among active duty service members and identified military and psychosocial factors associated with their development. Millennium Cohort Study participants were followed for up to 15 years and prevalence was ascertained using survey and electronic medical record data. Longitudinal multivariable logistic regression models evaluated risk factors associated with the development of bulimia nervosa (n=96,245) or binge eating disorder (n=113,733). Weighted prevalence estimates from survey data (range, 0.80%-4.80%) were higher than those from medical records (0.04%-0.14%). Military factors significantly associated with increased risk for BN and BED included active duty component (vs Reserve/Guard); serving in the Army, Marines, or Navy/Coast Guard (vs Air Force); and combat deployment (vs deployment without combat). Associated psychosocial factors included lack of social support, experiencing at least one life stressor, and screening positive for posttraumatic stress disorder or problem drinking. Findings highlight the critical need for disordered eating screening and prevention efforts that bolster coping skills, which can ultimately improve service member functioning and readiness.

Racial, Ethnic, and Sex Disparities in Mental Health Among US Service Members and Veterans: Findings From the Millennium Cohort Study.

Although disparities in mental health occur within racially, ethnically, and sex-diverse civilian populations, it is unclear whether these disparities persist within US military populations. Using cross-sectional data from the Millennium Cohort Study (2014-2016; n = 103,184; 70.3% male; 75.7% non-Hispanic White), a series of logistic regression analyses were conducted to examine whether racial, ethnic, and/or sex disparities were found in mental health outcomes (posttraumatic stress disorder (PTSD), depression, anxiety, and problematic anger), hierarchically adjusting for sociodemographic, military, health-related, and social support factors. Compared with non-Hispanic White individuals, those who identified as American Indian/Alaska Native, non-Hispanic Black, Hispanic/Latino, or multiracial showed greater risk of PTSD, depression, anxiety, and problematic anger in unadjusted models. Racial and ethnic disparities in mental health were partially explained by health-related and social support factors. Women showed greater risk of depression and anxiety and lower risk of PTSD than men. Evidence of intersectionality emerged for problematic anger among Hispanic/Latino and Asian or Pacific Islander women. Overall, racial, ethnic, and sex disparities in mental health persisted among service members and veterans. Future research and interventions are recommended to reduce these disparities and improve the health and well-being of diverse service members and veterans.

Sleep health among US Navy afloat versus ashore personnel in the Millennium Cohort Study.

Despite emerging public concern regarding the sleep health of military personnel over the past two decades, there remains a dearth of research examining sleep health among naval personnel assigned to sea duty. This study examined sleep metrics (e.g. fatigue, short sleep duration) and mental (e.g. posttraumatic stress disorder, depression) and physical health (e.g. type 2 diabetes, bodily pain) outcomes among naval personnel with recent sea duty (i.e. afloat) compared with naval personnel with recent shore duty (i.e. ashore). Prevalence ratios and mean differences for all outcomes were estimated and adjusted for demographic and military variables, and subsequently stratified by obesity. Sleep metrics were similar between afloat and ashore sailors except for short sleep duration, while sailors with recent shore duty had poorer physical health compared with those with recent sea duty. Stratified analyses suggested naval personnel with obesity had a higher proportion of nearly all adverse sleep-related health outcomes than those without obesity. Among participants without obesity, afloat personnel were more likely to report very short sleep (≤ 5 hours) and fewer hours of average nightly sleep, but were less likely to report physical health outcomes compared with ashore personnel. These findings suggest potential differences in sleep metrics and sleep-related health outcomes between afloat and ashore naval personnel. Additional research examining sleep outcomes using more objective measures is required to further investigate these findings, which may inform strategies to foster consolidated sleep despite environmental and occupational challenges in order to maintain high-performing naval personnel.

Risk of Traumatic Brain Injury in Deployment and Nondeployment Settings Among Members of the Millennium Cohort Study.

OBJECTIVE: To describe and quantify the prevalence and risk of deployment and nondeployment service-related traumatic brain injury (TBI) among participants of the Millennium Cohort Study. SETTING: Survey data. PARTICIPANTS: 28 759 Millennium Cohort Study participants who were active duty, Reserves, or National Guard at the time of the survey. DESIGN: Cross-sectional secondary data analysis. MAIN MEASURES: Estimates of prevalence and rates of TBI were calculated. Multivariable Poisson regression estimated rate ratios of TBI overall and stratified by deployment and nondeployment settings. RESULTS: The rate of TBI over the 362 535 person-years (PY) was 2.95 p/100 PY. the nondeployment rate was 2.15 p/100 PY, with a significantly higher rate (11.38 p/100 PY) in deployment settings. Bullets/blasts were the most common TBI mechanisms in deployed settings, while sports/physical training and military training were common in nondeployed settings. CONCLUSIONS: The risk of TBI as well as its mechanism varies by deployment and nondeployment, suggesting that targeted prevention strategies are needed to reduce the risk for TBI among military personnel based on their deployment status.

Posttraumatic stress disorder, Veterans Health Administration use, and care-seeking among recent-era U.S. veterans.

The current study investigated the associations among probable posttraumatic stress disorder (PTSD), recent Veterans Health Administration (VHA) health care use, and care-seeking for PTSD in U.S. military veterans. Analyses were conducted among 19,691 active duty military personnel enrolled in the Millennium Cohort Study who separated from the military between 2000 and 2012 and were weighted to the 1,130,103 active duty personnel who separated across this time period. VHA utilization was identified from electronic medical records in the year before survey completion, and PTSD care-seeking and PTSD symptoms were assessed through self-report on the 2014-2016 survey; thus, the observation period regarding care-seeking and VHA use encompassed 2013-2016. Veterans with probable PTSD were more likely to use VHA services than those without probable PTSD, aOR = 1.12, 95% CI [1.01, 1.24], although the strongest association with recent VHA use was a depression diagnosis, aOR = 2.47, 95% CI [2.26, 2.70]. Among veterans with probable PTSD, the strongest predictor of care-seeking was recent VHA use compared to community care, aOR = 4.01, 95% CI [3.40, 4.74); reporting a diagnosis of depression was the second strongest predictor of PTSD care-seeking, OR = 2.99, 95% CI [2.53, 3.54]. However, the absolute number of veterans with probable PTSD who were not seeking care was approximately equivalent between veterans using VHA services and those not using VHA services. Additionally, certain groups were identified as being at risk of not seeking care, namely Air Force veterans and veterans with high physical and mental functioning despite substantial PTSD symptoms.

Survey response over 15 years of follow-up in the Millennium Cohort Study.

BACKGROUND: Patterns of survey response and the characteristics associated with response over time in longitudinal studies are important to discern for the development of tailored retention efforts aimed at minimizing response bias. The Millennium Cohort Study, the largest and longest running cohort study of military personnel and veterans, is designed to examine the long-term health effects of military service and experiences and thus relies on continued participant survey responses over time. Here, we describe the response rates for follow-up survey data collected over 15 years and identify characteristics associated with follow-up survey response and mode of response (paper vs. web). METHOD: Patterns of follow-up survey response and response mode (web, paper, none) were examined among eligible participants (n=198,833), who were initially recruited in four panels from 2001 to 2013 in the Millennium Cohort Study, for a follow-up period of 3-15 years (2004-2016). Military and sociodemographic factors (i.e., enrollment panel, sex, birth year, race and ethnicity, educational attainment, marital status, service component, service branch, pay grade, military occupation, length of service, and time deployed), life experiences and health-related factors (i.e., military deployment/combat experience, life stressors, mental health, physical health, and unhealthy behaviors) were used to examine follow-up response and survey mode over time in multivariable generalized estimating equation models. RESULTS: Overall, an average response rate of 60% was observed across all follow-up waves. Factors associated with follow-up survey response over time included increased educational attainment, married status, female sex, older age, military deployment (regardless of combat experience), and higher number of life stressors, mental health issues, and physical health diagnoses. CONCLUSION: Despite the challenges associated with collecting multiple waves of follow-up survey data from members of the U.S. military during and after service, the Millennium Cohort Study has maintained a relatively robust response rate over time. The incorporation of tailored messages and outreach to those groups least likely to respond over time may improve retention and thereby increase the representativeness and generalizability of collected survey data.

A temporal analysis of mental health symptoms relative to separation from the military.

BACKGROUND: The transition from military to civilian life is a dramatic change that is often stressful for veterans. However, little is known regarding how mental health symptoms fluctuate in the period leading up to and following separation from the military. METHODS: The current study examined posttraumatic stress disorder and depression symptoms reported on surveys completed within 1 year of military separation from 23,887 active duty Millennium Cohort Study participants. A series of general linear models and graphs stratified by demographic and military characteristics examined the association between time until/since separation and mental health symptoms. RESULTS: Character of discharge had the most striking relationship between time until/since separation and mental health. Personnel with Honorable discharges did not differ in their level of mental health symptoms across the study period. In contrast, personnel with Other than Honorable/General discharges reported normal levels of mental health symptoms 1 year-prior to separation but reported progressively greater symptoms leading to separation which persisted through the remainder of study period. CONCLUSIONS: This study suggests that additional outreach is needed for personnel with Other than Honorable/General discharges. However, for most other personnel, increased mental health symptomatology around military separation is not a normative phenomenon and any instance should be treated promptly.

Clinical profile of children incidentally found to have advanced kidney failure.

INTRODUCTION: No data exist on the epidemiology of children incidentally diagnosed with advanced kidney failure (KF) during evaluation for non-specific symptoms. This is likely related to unrecognized symptoms and signs of CKD. The objective of our study was to evaluate incidentally diagnosed patients with advanced KF requiring long-term kidney replacement therapy (KRT). METHODS: An IRB-approved retrospective chart review of children who started KRT with dialysis (hemo- or peritoneal) was conducted. Included were children with no prior knowledge or diagnosis of underlying kidney disease with chronic kidney disease (CKD) disease stage 4 (GFR 15-29 mL/min/1.73 m2) or 5 (GFR < 15 mL/min/1.73 m2) at initial presentation and started on chronic KRT within 2 months of presentation. RESULTS: Of 177 patients initiating KRT during the study period, 26 (15%) were categorized as incidental advanced KF. This cohort with mean age 12.25 years consisted of 42% males, 54% African Americans included 46% with glomerular, and 54% with non-glomerular etiology for kidney failure. Vomiting (42%) and fatigue (39%) were most common, while growth failure (19%) and hyperkalemia (7%) were less frequent on initial presentation. Anemia (100%), hypertension (96%), hyperparathyroidism (96%), and hyperphosphatemia (92%) were the most frequently seen CKD comorbidities. Chronic KRT was started within 24 h in 62% and within 2 weeks in 88% of the cohort. CONCLUSION: Under-diagnosis of patients with advanced KF is most likely related to milder non-specific clinical symptoms and normal growth in the majority of patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

Military service experiences and reasons for service separation among lesbian, gay, and bisexual individuals in a large military cohort.

BACKGROUND: The well-being of lesbian, gay, and bisexual (LGB) individuals is a topic of increasing concern within the military where significant institutional barriers, targeted aggression, and differential organizational policies such as "Don't Ask Don't Tell" have historically contributed to experiences of exclusion and discrimination. However, limited research has examined specific military and post-separation experiences among LGB service members and veterans. The goal of this study was to examine differences in military and service separation experiences by sexual orientation among a large representative sample of United States service members and veterans. METHODS: Survey data from the 2016 Millennium Cohort Study follow-up questionnaire were used to assess sexual orientation and multiple outcomes of interest: military experiences (morale, feelings about the military, missed workdays) and service separation experiences (reasons for separation, post-separation employment). The associations between sexual orientation (LGB versus heterosexual) and each of these outcomes were evaluated in a series of adjusted logistic regression models, stratified by sex when interactions were observed. RESULTS: Of the 99,599 participants, 3.4% identified as LGB. In adjusted models, LGB service members had significantly higher odds than heterosexual service members of feeling: unimpressed by the quality of unit leadership, unsupported by the military, and negative about the military overall. Bisexual women were more likely than heterosexual women to feel less unit camaraderie; both gay and bisexual men felt less camaraderie than heterosexual men. LGB veterans were more likely than heterosexual peers of the same sex to separate from service due to unplanned administrative reasons. Compared to heterosexual women, lesbian and bisexual women were more likely to separate from service due to dissatisfaction with promotions/pay and disability/medical reasons, while bisexual women specifically separated due to dissatisfaction with leadership and incompatibility with the military. Gay and bisexual men also reported separating due to incompatibility with the military, but only bisexual men were more likely to report separating due to disability/medical reasons compared to heterosexual men. CONCLUSIONS: Less positive military- and separation-specific experiences disproportionately affected LGB service members in this study. Promoting inclusion and increasing support for LGB service members may improve satisfaction with military service and retention.

Multiple imputation validation study: addressing unmeasured survey data in a longitudinal design.

BACKGROUND: Questionnaires used in longitudinal studies may have questions added or removed over time for numerous reasons. Data missing completely at a follow-up survey is a unique issue for longitudinal studies. While such excluded questions lack information at one follow-up survey, they are collected at other follow-up surveys, and covariances observed at other follow-up surveys may allow for the recovery of the missing data. This study utilized data from a large longitudinal cohort study to assess the efficiency and feasibility of using multiple imputation (MI) to recover this type of information. METHODS: Millennium Cohort Study participants completed the 9-item Patient Health Questionnaire (PHQ) depression module at 2 time points (2004, 2007). The suicidal ideation item in the module was set to missing for the 2007 assessment. Several single-level MI models using different sets of predictors and forms of suicidal ideation were used to compare self-reported values and imputed values for this item in 2007. Additionally, associations with sleep duration and smoking status, which are related constructs, were compared between self-reported and imputed values of suicidal ideation. RESULTS: Among 63,028 participants eligible for imputation analysis, 4.05% reported suicidal ideation on the 2007 survey. The imputation models successfully identified suicidal ideation, with a sensitivity ranging between 34 and 66% and a positive predictive value between 36 and 42%. Specificity remained above 96% and negative predictive value above 97% for all imputed models. Similar associations were found for all imputation models on related constructs, though the dichotomous suicidal ideation imputed from the model using only PHQ depression items yielded estimates that were closest with the self-reported associations for all adjusted analyses. CONCLUSIONS: Although sensitivity and positive predictive value were relatively low, applying MI techniques allowed for inclusion of an otherwise missing variable. Additionally, correlations with related constructs were estimated near self-reported values. Therefore, the other 8 depression items can be used to estimate suicidal ideation that was completely missing from a survey using MI. However, these imputed values should not be used to estimate population prevalence.

APOL1-Associated Collapsing Focal Segmental Glomerulosclerosis in a Patient With Stimulator of Interferon Genes (STING)-Associated Vasculopathy With Onset in Infancy (SAVI).

Apolipoprotein L1 (APOL1) risk variants G1 and G2 are known to result in risk for kidney disease in patients of African ancestry. APOL1-associated nephropathy typically occurs in association with certain environmental factors or systemic diseases. As such, there has been increasing evidence of the role of interferon (IFN) pathways in the pathogenesis of APOL1-associated collapsing glomerulopathy in patients with human immunodeficiency virus (HIV) infection and systemic lupus erythematosus, 2 conditions that are associated with high IFN levels. Collapsing glomerulopathy has also been described in patients receiving exogenous IFN therapy administered for various medical conditions. We describe a patient with a genetic condition that results in an increased IFN state, stimulator of IFN genes (STING)-associated vasculopathy with onset in infancy (SAVI), who developed collapsing glomerulopathy during a flare of his disease. The patient was found to have APOL1 G1 and G2 risk variants. This case supports the role of IFN in inducing APOL1-associated collapsing glomerulopathy.

KDOQI Clinical Practice Guideline for Vascular Access: 2019 Update.

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has provided evidence-based guidelines for hemodialysis vascular access since 1996. Since the last update in 2006, there has been a great accumulation of new evidence and sophistication in the guidelines process. The 2019 update to the KDOQI Clinical Practice Guideline for Vascular Access is a comprehensive document intended to assist multidisciplinary practitioners care for chronic kidney disease patients and their vascular access. New topics include the end-stage kidney disease "Life-Plan" and related concepts, guidance on vascular access choice, new targets for arteriovenous access (fistulas and grafts) and central venous catheters, management of specific complications, and renewed approaches to some older topics. Appraisal of the quality of the evidence was independently conducted by using a Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, and interpretation and application followed the GRADE Evidence to Decision frameworks. As applicable, each guideline statement is accompanied by rationale/background information, a detailed justification, monitoring and evaluation guidance, implementation considerations, special discussions, and recommendations for future research.

Urinary cadmium and timing of menarche and pubertal development in girls.

BACKGROUND: Cadmium (Cd) is a developmental toxicant that is released into the environment during industrial processes. Previous animal studies suggest that Cd may impact the onset of puberty. OBJECTIVES: To determine whether Cd exposure, measured as urinary Cd concentration, was associated with ages at menarche and pubertal development. METHODS: A cohort of 211 girls, ages 10-13 years at baseline, was followed for up to two years. Girls completed an interview and self-assessment of Tanner stages of breast development and pubic hair growth. They were followed monthly until menarche. Urinary Cd concentrations were measured in overnight urine specimens. Multivariable Cox regression was used to evaluate the association between urinary Cd and age at menarche and cumulative logit regression was used to evaluate the associations between urinary Cd and breast development and pubic hair growth. RESULTS: The baseline geometric mean creatinine-adjusted Cd concentration was 0.22 µg/g creatinine (geometric standard deviation = 1.6) and decreased with increasing age (p-trend = 0.04). Cd levels were higher among Asian than White girls or girls of other/mixed race/ethnicity (p = 0.04). In multivariable analyses, girls with urinary Cd ≥ 0.4 µg/L were less likely to have attained menarche than girls with urinary Cd < 0.2 µg/L (hazard ratio = 0.42; 95% confidence interval, 0.23-0.78). Urinary Cd was negatively associated with pubic hair growth (p-trend = 0.01) but not with breast development (p-trend = 0.72) at baseline. CONCLUSIONS: These findings suggest that a higher Cd body burden may delay some aspects of pubertal development among girls.

Posttraumatic stress disorder and risk of selected autoimmune diseases among US military personnel.

BACKGROUND: Increasing evidence suggests a link between posttraumatic stress disorder (PTSD) and physical health. Stress disorders may lead to impairment of the immune system and subsequent autoimmune disease. This study investigated the association between PTSD and risk of selected autoimmune diseases (i.e. rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, and multiple sclerosis) among US active duty service members. METHODS: Using data from the Millennium Cohort Study, incident autoimmune cases between study initiation and September 2015 were identified from medical encounter records in the Military Health System Data Repository (MDR). Participants were classified as having a history of PTSD if they self-reported receiving a health care provider's diagnosis of PTSD or if they screened positive using the PTSD Checklist-Civilian Version. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models adjusted for demographics and history of another mental health condition. RESULTS: Among 120,572 participants followed for a mean of 5.2 years, risk of any of the selected autoimmune diseases was 58% higher for those with a history of PTSD (HR = 1.58, 95% CI: 1.25, 2.01) compared with no history of PTSD. Further adjustment for BMI, smoking status, and alcohol use had little impact on the effect estimates, and results were not appreciably different according to combat experience and history of physical or sexual trauma. CONCLUSIONS: Active duty military personnel with PTSD may have an elevated risk of a range of autoimmune diseases, regardless of combat experience or prior trauma. Future research is needed to understand potential mechanisms which may inform future mitigative strategies in reducing extra-neuropsychiatric health problems among those with PTSD.

New-Onset Asthma and Combat Deployment: Findings From the Millennium Cohort Study.

Recent reports suggest US military service members who deployed in support of the recent conflicts in Iraq and Afghanistan have higher rates of new-onset asthma than those who did not deploy. However, it is unknown whether combat experiences, in addition to deployment, contribute to new-onset asthma risk. This study aimed to longitudinally determine the risk factors for developing asthma, including combat deployment (categorized as deployed with combat experience, deployed without combat experience, or nondeployed), among participants in the Millennium Cohort Study from 2001 to 2013. A total of 75,770 participants completed a baseline survey and at least 1 triennial follow-up survey on deployment experiences, lifestyle characteristics, and health outcomes. Complementary log-log models stratified by sex were used to estimate the relative risk of developing asthma among participants who reported no history of asthma at baseline. In models with adjustments, those who deployed with combat experience were 24%-30% more likely to develop asthma than those who did not deploy. Deployed personnel without combat experience were not at a higher risk for new-onset asthma compared with nondeployers. Further research is needed to identify specific features of combat that are associated with greater asthma risk to inform prevention strategies.

Dialysis in Children and Adolescents: The Pediatric Nephrology Perspective.

The care of children with end-stage renal disease (ESRD) is highly specialized and often poorly understood by nonpediatric providers and facility/institution administrators. As such, this position paper has been created to offer provider, facility, and institutional guidance regarding the components of care necessary for children receiving dialysis. Key differences between adult and pediatric dialysis units are highlighted. Responsibilities and expectations of the members of the interdisciplinary dialysis team are outlined as they pertain specifically to the care of pediatric dialysis patients. Physical and staffing requirements of the dialysis facility are reviewed, again focusing on unique needs and challenges faced by the pediatric dialysis care team. Among these, vascular access options and proper planning of ESRD care are underscored. Pediatric quality-of-life metrics differ significantly from adult quality variables, and proper tools for assessment must be used. Endorsed by the Council of the American Society of Pediatric Nephrology (ASPN), this position paper serves as a reference tool for the provision of care to pediatric patients with ESRD.

Short-term Results of the RAPID Randomized Trial of the Legflow Paclitaxel-Eluting Balloon With Supera Stenting vs Supera Stenting Alone for the Treatment of Intermediate and Long Superficial Femoral Artery Lesions.

PURPOSE: To report a randomized trial comparing the Legflow paclitaxel-eluting balloon (PEB) + Supera stenting to Supera stenting alone in patients with intermediate to long superficial femoral artery (SFA) lesions. METHODS: The multicenter RAPID trial ( controlled-trials.com ; identifier ISRCTN47846578) randomized (1:1) 160 patients (mean age 67 years; 102 men) with Rutherford category 2-6 ischemia to treatment with Legflow PEB + Supera stent or Supera stent alone in intermediate to long SFA lesions (mean lesion length 15.8±7.4 vs 15.8±7.6 cm, respectively). The efficacy outcome was primary patency, defined as freedom from restenosis on duplex ultrasound or angiography. RESULTS: Baseline characteristics including the percentage of occlusions were similar between groups. In the intention-to-treat analysis, the estimated primary patency at 1 year was 68.3% (95% CI 56.7% to 79.9%) in the PEB + Supera group vs 62.0% (95% CI 49.1% to 74.9%) in the Supera group (p=0.900). Per-protocol analysis showed a 12-month primary patency estimate of 74.7% (95% CI 63.1% to 86.3%) in the PEB + Supera group vs 62.0% (95% CI 49.1% to 74.9%) in the control group (p=0.273). Secondary patency estimates at 12 months (per-protocol analysis) were 89.0% (95% CI 80.6% to 97.4%) vs 98.0% (95% CI 94.1% to 100%; p=0.484); the estimates for freedom from clinically driven target lesion revascularization (CD-TLR) were 83.0% (95% CI 72.8% to 93.2%) and 77.8% (95% CI 66.6% to 89.0%; p=0.277), respectively. CONCLUSION: The short-term results from the multicenter RAPID randomized controlled trial indicate that the Legflow PEB is safe and feasible for the treatment of intermediate to long SFA lesions. In this trial, at least 70% of the patients suffered an occlusion. The PEB group had higher rates of primary patency and freedom from CD-TLR, although there were no statistically significant differences vs controls.