Small RNA Sequencing across Diverse Biofluids Identifies Optimal Methods for exRNA Isolation.

Poor reproducibility within and across studies arising from lack of knowledge regarding the performance of extracellular RNA (exRNA) isolation methods has hindered progress in the exRNA field. A systematic comparison of 10 exRNA isolation methods across 5 biofluids revealed marked differences in the complexity and reproducibility of the resulting small RNA-seq profiles. The relative efficiency with which each method accessed different exRNA carrier subclasses was determined by estimating the proportions of extracellular vesicle (EV)-, ribonucleoprotein (RNP)-, and high-density lipoprotein (HDL)-specific miRNA signatures in each profile. An interactive web-based application (miRDaR) was developed to help investigators select the optimal exRNA isolation method for their studies. miRDar provides comparative statistics for all expressed miRNAs or a selected subset of miRNAs in the desired biofluid for each exRNA isolation method and returns a ranked list of exRNA isolation methods prioritized by complexity, expression level, and reproducibility. These results will improve reproducibility and stimulate further progress in exRNA biomarker development.

Tear Proteins Altered in Patients with Persistent Eye Pain after Refractive Surgery: Biomarker Candidate Discovery.

Some patients develop persistent eye pain after refractive surgery, but factors that cause or sustain pain are unknown. We tested whether tear proteins of patients with pain 3 months after surgery differ from those of patients without pain. Patients undergoing refractive surgery (laser in situ keratomileusis or photorefractive keratectomy ) were recruited from 2 clinics, and tears were collected 3 months after surgery. Participants rated their eye pain using a numerical rating scale (NRS, 0-10; no pain-worst pain) at baseline, 1 day, and 3 months after surgery. Using tandem mass tag proteomic analysis, we examined tears from patients with pain [NRS ≥ 3 at 3 months (n = 16)] and patients with no pain [NRS ≤ 1 at 3 months (n = 32)] after surgery. A subset of proteins (83 of 2748 detected, 3.0%) were associated with pain 3 months after surgery. High-dimensional statistical models showed that the magnitude of differential expression was not the only important factor in classifying tear samples from pain patients. Models utilizing 3 or 4 proteins had better classification performance than single proteins and represented differences in both directions (higher or lower in pain). Thus, patterns of protein differences may serve as biomarkers of postsurgical eye pain as well as potential therapeutic targets.

Latent phase duration and associated outcomes: a contemporary, population-based observational study.

BACKGROUND: Little is known about the latent phase of labor, including whether its duration influences subsequent labor processes or birth outcomes. OBJECTIVE: This study aimed to describe the duration of the latent phase of labor from self-report of the onset of painful contractions to a cervical dilation of 5 cm in a large, Swedish population and evaluate the association between the duration of the latent phase of labor and perinatal processes and outcomes that occurred during the active phase of labor, second stage of labor, birth and immediately after delivery, stratified by parity. STUDY DESIGN: This was a population-based cohort study of 67,267 pregnancies with deliveries between 2008 and 2020 in the Stockholm-Gotland Regions, Sweden. Nulliparous and parous women without a history of cesarean delivery in spontaneous labor with a term (≥37 weeks of gestation), singleton, live, and vertex fetus without major malformations were included. Imputation was used if the notation of the end of the latent phase of labor (ie, cervical dilation of 5 cm) was missing in the partograph. Multivariable logistic regression was used to estimate the association with adjusted odds ratios and 95% confidence intervals, controlling for potential covariates. RESULTS: Including the time from painful contraction onset to a cervical dilation of 5 cm, the median durations of the latent phase of labor were 16.0 (interquartile range, 10.0-26.6) hours for nulliparous women and 9.4 (interquartile range, 5.9-15.3) hours for multiparous women. The durations of the latent phase of labor beyond the median were associated with increased odds of labor dystocia diagnosis during the first stage active phase or second stage of labor and interventions commonly associated with dystocia (amniotomy, oxytocin augmentation, epidural, and cesarean delivery). The duration of the latent phase of labor of ≥90th percentile vs less than the median in nulliparous women demonstrated an increased risk of adverse neonatal outcomes (Apgar score of <7 at 5 minutes and neonatal intensive care unit admission), chorioamnionitis, and fetal occiput posterior. In multiparous women, longer duration of the latent phase of labor was associated with an increased risk of neonatal intensive care unit admission and chorioamnionitis but was not associated with an Apgar score of <7 at 5 minutes. The duration of the latent phase of labor was not associated with additional markers of maternal risk. CONCLUSION: The duration of the latent phase of labor in nulliparous women was longer than that of multiparous women at each point of distribution. A longer duration of the latent phase of labor was associated with more frequent dystocia diagnoses and related interventions during the first stage active phase or second stage of labor, including cesarean delivery, nulliparous fetal occiput posterior position, chorioamnionitis, and markers of neonatal morbidity. More research is needed to identify potential mediating paths between the duration of the latent phase of labor and neonatal morbidity.

Mobility Rehab visual feedback system for gait rehabilitation in older adults.

BACKGROUND: Gait and balance impairments are among the main causes of falls in older adults. The feasibility and effectiveness of adding sensor-based feedback to physical therapy (PT) in an outpatient PT setting is unknown. We evaluated the feasibility and effectiveness of PT intervention combined with a therapist-assisted visual feedback system, called Mobility Rehab, (PT + MR) in older adults. METHODS: Twenty-eight older adults with and without neurological diseases were assigned either PT + MR (n = 22) or PT alone (n = 6). Both groups performed 8 sessions (individualized) of 45 min long (30 min for gait training and 15 min for endurance, strength, and balance exercises) in an outpatient clinic. Mobility Rehab uses unobtrusive, inertial sensors on both wrists and feet, and at the sternum level with real-time algorithms to provide real-time feedback on five gait metrics (step duration, stride length, elevation at mid-swing, arm swing range-of-motion [ROM], and trunk coronal ROM), which are displayed on a tablet. The primary outcome was the Activities-specific Balance Confidence scale (ABC). The secondary outcome was gait speed measured with wearable inertial sensors during 2 min of walking. RESULTS: There were no between-group differences at baseline for any variable (P > 0.05). Neither PT + MR nor PT alone showed significant changes on the ABC scores. PT + MR, but not PT alone, showed significant improvements in gait speed and arm swing ROM. The system was evaluated as 'easy to use' by the PT. CONCLUSIONS: Our preliminary results show that PT + MR improves gait speed in older adults with and without neurological diseases in an outpatient clinic. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov , identifier: NCT03869879.

Individual and joint trajectories of change in bone, lean mass and physical performance in older men.

BACKGROUND: Declines in bone, muscle and physical performance are associated with adverse health outcomes in older adults. However, few studies have described concurrent age-related patterns of change in these factors. The purpose of this study was to characterize change in four properties of muscle, physical performance, and bone in a prospective cohort study of older men. METHODS: Using repeated longitudinal data from up to four visits across 6.9 years from up to 4681 men (mean age at baseline 72.7 yrs. ±5.3) participating in the Osteoporotic Fractures in Men (MrOS) Study, we used group-based trajectory models (PROC TRAJ in SAS) to identify age-related patterns of change in four properties of muscle, physical performance, and bone: total hip bone mineral (BMD) density (g/m2) and appendicular lean mass/ht2 (kg/m2), by DXA; grip strength (kg), by hand dynamometry; and walking speed (m/s), by usual walking pace over 6 m. We also described joint trajectories in all pair-wise combinations of these measures. Mean posterior probabilities of placement in each trajectory (or joint membership in latent groups) were used to assess internal reliability of the model. The number of trajectories for each individual factor was limited to three, to ensure that the pair-wise determination of joint trajectories would yield a tractable number of groups as well as model fit considerations. RESULTS: The patterns of change identified were generally similar for all measures, with three district groups declining over time at roughly similar rates; joint trajectories revealed similar patterns with no cross-over or convergence between groups. Mean posterior probabilities for all trajectories were similar and consistently above 0.8 indicating reasonable model fit to the data. CONCLUSIONS: Our description of trajectories of change with age in bone mineral density, grip strength, walking speed and appendicular lean mass found that groups identified by these methods appeared to have little crossover or convergence of change with age, even when considering joint trajectories of change in these factors.

Improvements in hospice utilization among patients with advanced-stage lung cancer in an integrated health care system.

BACKGROUND: Hospice, a patient-centered care system for those with limited life expectancy, is important for enhancing quality of life and is understudied in integrated health care systems. METHODS: This was a retrospective cohort study of 21,860 decedents with advanced-stage lung cancer diagnosed from January 2007 to June 2013 in the national US Veterans Affairs Health Care System. Trends over time, geographic regional variability, and patient and tumor characteristics associated with hospice use and the timing of enrollment were examined. Multivariable logistic regression and Cox proportional hazards modeling were used. RESULTS: From 2007 to 2013, 70.3% of decedents with advanced-stage lung cancer were enrolled in hospice. Among patients in hospice, 52.9% were enrolled in the last month of life, and 14.7% were enrolled in the last 3 days of life. Hospice enrollment increased (adjusted odds ratio [AOR], 1.07; P < .001), whereas the mean time from the cancer diagnosis to hospice enrollment decreased by 65 days (relative decrease, 32%; adjusted hazard ratio, 1.04; P < .001). Relative decreases in late hospice enrollment were observed in the last month (7%; AOR, 0.98; P = .04) and last 3 days of life (26%; AOR, 0.95; P < .001). The Southeast region of the United States had both the highest rate of hospice enrollment and the lowest rate of late enrollment. Patient sociodemographic and lung cancer characteristics were associated with hospice enrollment. CONCLUSIONS: Among patients with advanced-stage lung cancer in the Veterans Affairs Health Care System, overall and earlier hospice enrollment increased over time. Considerable regional variability in hospice enrollment and the persistence of late enrollment suggests opportunities for improvement in end-of-life care. Cancer 2018;124:426-33. © 2017 American Cancer Society.

Vaginal birth after cesarean: neonatal outcomes and United States birth setting.

BACKGROUND: Women who seek vaginal birth after cesarean delivery may find limited in-hospital options. Increasing numbers of women in the United States are delivering by vaginal birth after cesarean delivery out-of-hospital. Little is known about neonatal outcomes among those who deliver by vaginal birth after cesarean delivery in- vs out-of-hospital. OBJECTIVE: The purpose of this study was to compare neonatal outcomes between women who deliver via vaginal birth after cesarean delivery in-hospital vs out-of-hospital (home and freestanding birth center). STUDY DESIGN: We conducted a retrospective cohort study using 2007-2010 linked United States birth and death records to compare singleton, term, vertex, nonanomolous, and liveborn neonates who delivered by vaginal birth after cesarean delivery in- or out-of-hospital. Descriptive statistics and multivariate regression analyses were conducted to estimate unadjusted, absolute, and relative birth-setting risk differences. Analyses were stratified by parity and history of vaginal birth. Sensitivity analyses that involved 3 transfer status scenarios were conducted. RESULTS: Of women in the United States with a history of cesarean delivery (n=1,138,813), only a small proportion delivered by vaginal birth after cesarean delivery with the subsequent pregnancy (n=109,970; 9.65%). The proportion of home vaginal birth after cesarean delivery births increased from 1.78-2.45%. A pattern of increased neonatal morbidity was noted in unadjusted analysis (neonatal seizures, Apgar score <7 or <4, neonatal seizures), with higher morbidity noted in the out-of-hospital setting (neonatal seizures, 23 [0.02%] vs 6 [0.19%; P<.001]; Apgar score <7, 2859 [2.68%] vs 139 [4.42%; P<.001; Apgar score <4, 431 [0.4%] vs 23 [0.73; P=.01]). A similar, but nonsignificant, pattern of increased risk was observed for neonatal death and ventilator support among those neonates who were born in the out-of-hospital setting. Multivariate regression estimated that neonates who were born in an out-of-hospital setting had higher odds of poor outcomes (neonatal seizures [adjusted odds ratio, 8.53; 95% confidence interval, 2.87-25.4); Apgar score <7 [adjusted odds ratio, 1.62; 95% confidence interval, 1.35-1.96]; Apgar score <4 [adjusted odds ratio, 1.77; 95% confidence interval, 1.12-2.79]). Although the odds of neonatal death (adjusted odds ratio, 2.1; 95% confidence interval, 0.73-6.05; P=.18) and ventilator support (adjusted odds ratio, 1.36; 95% confidence interval, 0.75-2.46) appeared to be increased in out-of-hospital settings, findings did not reach statistical significance. Women birthing their second child by vaginal birth after cesarean delivery in out-of-hospital settings had higher odds of neonatal morbidity and death compared with women of higher parity. Women who had not birthed vaginally prior to out-of-hospital vaginal birth after cesarean delivery had higher odds of neonatal morbidity and mortality compared with women who had birthed vaginally prior to out-of-hospital vaginal birth after cesarean delivery. Sensitivity analyses generated distributions of plausible alternative estimates by outcome. CONCLUSION: Fewer than 1 in 10 women in the United States with a previous cesarean delivery delivered by vaginal birth after cesarean delivery in any setting, and increasing proportions of these women delivered in an out-of-hospital setting. Adverse outcomes were more frequent for neonates who were born in an out-of-hospital setting, with risk concentrated among women birthing their second child and women without a history of vaginal birth. This information urgently signals the need to increase availability of in-hospital vaginal birth after cesarean delivery and suggests that there may be benefit associated with increasing options that support physiologic birth and may prevent primary cesarean delivery safely. Results may inform evidence-based recommendations for birthplace among women who seek vaginal birth after cesarean delivery.

Lower Urinary Tract Symptoms and Risk of Nonspine Fractures among Older Community Dwelling U.S. Men.

PURPOSE: Among older men, moderate and severe lower urinary tract symptoms are associated with increased fall risk compared to mild lower urinary tract symptoms. Falls are a major risk factor for fractures. Therefore, we assessed associations of lower urinary tract symptoms with fracture risk in community dwelling U.S. men age 65 years or older. MATERIALS AND METHODS: We conducted a prospective study in the MrOS (Osteoporotic Fractures in Men Study) cohort. Men were enrolled at 6 U.S. sites. The AUA-SI, lower urinary tract symptoms medication use, fracture risk factors and potential confounders were recorded at baseline and every 2 years thereafter for 4 assessments. Lower urinary tract symptom severity was categorized from the AUA-SI as mild (0 to 7 points), moderate (8 to 19 points) or severe (20 or more points). Associations of lower urinary tract symptom severity with fracture rate were estimated with HRs and 95% CIs from extended proportional hazards regression. RESULTS: Among 5,989 men with baseline AUA-SI score and hip bone mineral density measures, 745 incident nonspine fractures occurred during 43,807 person-years of followup. In a multivariable model adjusted for age, enrollment site, baseline hip bone mineral density, falls in the last year and prevalent fracture before baseline, there were no significant associations of moderate (HR 0.9, 95% CI 0.8-1.1) or severe (HR 1.0, 95% CI 0.8-1.3) lower urinary tract symptoms with fracture risk. None of the individual lower urinary tract symptoms assessed on the AUA-SI, including nocturia and urgency, was associated with increased fracture risk. CONCLUSIONS: In this cohort of older U.S. men, lower urinary tract symptoms were not independently associated with fracture risk.

Two Years in the Life of a University Hospital Tobacco Cessation Service: Recommendations for Improving the Quality of Referrals.

BACKGROUND: Hospitalization, when patients may be more receptive to quitting, provides an opportunity to provide tobacco cessation services for patients who otherwise might not seek help. Although specialized tobacco cessation services are shown to be effective if evidence-based treatment, including follow-up, is completed, resources are limited and guidelines are needed, and few smokers complete all treatment steps. Experience drawn from an analysis of two-year implementation data from the Oregon Health & Science University (OHSU) Tobacco Cessation Consult Service is presented. METHODS: Data for 5,827 smokers discharged from OHSU University hospital between January 2011 and December 2012 were analyzed to determine patient characteristics and identify predictors of completing each of four treatment steps: consult ordered, consult completed, follow-up arranged, and follow-up completed. RESULTS: Smokers were younger and male (p<0.0001) and significantly different with respect to insurance class, admission type, history of mental disorders, primary discharge diagnoses, and length of stay (p<0.0001) than nonsmokers. Predictors of having a tobacco consult order were admission for elective medical procedures; orders for medications to treat withdrawal; history of mental health/substance use disorders; primary diagnoses of cardiovascular, endocrine, gastrointestinal, or pulmonary disease; and longer hospitalizations. Smokers admitted through the emergency department had the lowest rates of follow-up completion and abstinence. Admission for an elective surgery was the only predictor of completing all treatment steps through followup (p≤0.05). CONCLUSIONS: This study adds important information about how hospitalized smokers respond to each step of tobacco treatment in a real-world setting and offers strategies for improving referrals.

Aortic dimensions in Turner syndrome.

In Turner syndrome, linear growth is less than the general population. Consequently, to assess stature in Turner syndrome, condition-specific comparators have been employed. Similar reference curves for cardiac structures in Turner syndrome are currently unavailable. Accurate assessment of the aorta is particularly critical in Turner syndrome because aortic dissection and rupture occur more frequently than in the general population. Furthermore, comparisons to references calculated from the taller general population with the shorter Turner syndrome population can lead to over-estimation of aortic size causing stigmatization, medicalization, and potentially over-treatment. We used echocardiography to measure aortic diameters at eight levels of the thoracic aorta in 481 healthy girls and women with Turner syndrome who ranged in age from two to seventy years. Univariate and multivariate linear regression analyses were performed to assess the influence of karyotype, age, body mass index, bicuspid aortic valve, blood pressure, history of renal disease, thyroid disease, or growth hormone therapy. Because only bicuspid aortic valve was found to independently affect aortic size, subjects with bicuspid aortic valve were excluded from the analysis. Regression equations for aortic diameters were calculated and Z-scores corresponding to 1, 2, and 3 standard deviations from the mean were plotted against body surface area. The information presented here will allow clinicians and other caregivers to calculate aortic Z-scores using a Turner-based reference population. © 2015 Wiley Periodicals, Inc.

Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in women with preterm labor and intact membranes.

OBJECTIVE: Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). STUDY DESIGN: This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). RESULTS: MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. CONCLUSION: High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.

Effect of augmenting cholinergic function on gait and balance.

BACKGROUND: Impaired mobility and falls are clinically important complications of Parkinson's disease (PD) and a major detractor from quality of life for which there are limited therapies. Pathological, neuroimaging and clinical evidence suggest that degeneration of cholinergic systems may contribute to impairments of balance and gait in PD. The proposed trial will examine the effects of augmentation of the cholinergic system on balance and gait. DESIGN: The study is a single-site, proof of concept, randomized, double-blind, cross-over trial in patients with PD. Each treatment period will be 6 weeks with a 6-week washout between treatments for a total of 18 weeks for each subject. Donepezil in 2.5 mg capsules or identical appearing placebo capsules will be increased from two per day (5 mg) to four capsules (10 mg) after 3 weeks, if tolerated. Subjects will have idiopathic Parkinson's disease, Hoehn and Yahr stages 2 to 4. We anticipate recruiting up to 100 subjects for screening to have 54 enrolled and 44 subjects complete both phases of treatment. Dropouts will be replaced. As this is a crossover trial, all subjects will be exposed to both donepezil and to placebo. The primary outcome measures will be the root mean square of the mediolateral sway when standing and the variability of the stride duration when walking for two minutes. Secondary outcomes will be the computerized Attention Network Test to examine three domains of attention and the Short-latency Afferent Inhibition (SAI), a physiological marker obtained with transcranial magnetic stimulation as a putative marker of cholinergic activity. DISCUSSION: The results of this study will be the most direct test of the hypothesized role of cholinergic neurotransmission in gait and balance. The study is exploratory because we do not know whether donepezil will affect gait, balance or attention, nor which measures of gait, balance or attention will be sensitive to drug manipulation. We hypothesize that change in cholinergic activity, as measured with SAI, will predict the relative effectiveness of donepezil on gait and balance. Our immediate goal is to determine the potential utility of cholinergic manipulation as a strategy for preventing or treating balance and gait dysfunction in PD. The findings of this trial are intended to lead to more sharply focused questions about the role of cholinergic neurotransmission in balance and gait and eventually to Phase II B trials to determine clinical utility of cholinergic manipulation to prevent falls and improve mobility. TRIAL REGISTRATION: This trial is registered at clinical trials.gov ( NCT02206620).

Travel-associated antimicrobial drug-resistant nontyphoidal Salmonellae, 2004-2009.

To evaluate trends in and risk factors for acquisition of antimicrobial-drug resistant nontyphoidal Salmonella infections, we searched Oregon surveillance data for 2004-2009 for all culture-confirmed cases of salmonellosis. We defined clinically important resistance (CIR) as decreased susceptibility to ampicillin, ceftriaxone, ciprofloxacin, gentamicin, or trimethoprim/sulfamethoxazole. Of 2,153 cases, 2,127 (99%) nontyphoidal Salmonella isolates were obtained from a specific source (e.g., feces, urine, blood, or other normally sterile tissue) and had been tested for drug susceptibility. Among these, 347 (16%) isolates had CIR. The odds of acquiring CIR infection significantly increased each year. Hospitalization was more likely for patients with than without CIR infections. Among patients with isolates that had been tested, we analyzed data from 1,813 (84%) who were interviewed. Travel to eastern or Southeast Asia was associated with increased CIR. Isolates associated with outbreaks were less likely to have CIR. Future surveillance activities should evaluate resistance with respect to international travel.

Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes.

OBJECTIVE: The purpose of this study was to compare intraamniotic inflammation vs microbial invasion of the amniotic cavity (MIAC) as predictors of adverse outcome in preterm labor with intact membranes. STUDY DESIGN: Interleukin-6 (IL-6) was measured in prospectively collected amniotic fluid from 305 women with preterm labor. MIAC was defined by amniotic fluid culture and/or detection of microbial 16S ribosomal DNA. Cases were categorized into 5 groups: infection (MIAC; IL-6, ≥11.3 ng/mL); severe inflammation (no MIAC; IL-6, ≥11.3 ng/mL); mild inflammation (no MIAC; IL-6, 2.6-11.2 ng/mL); colonization (MIAC; IL-6, <2.6 ng/mL); negative (no MIAC; IL-6, <2.6 ng/mL). RESULTS: The infection (n = 27) and severe inflammation (n = 36) groups had similar latency (median, <1 day and 2 days, respectively) and similar rates of composite perinatal morbidity and mortality (81% and 72%, respectively). The colonization (n = 4) and negative (n = 195) groups had similar outcomes (median latency, 23.5 and 25 days; composite morbidity and mortality rates, 21% and 25%, respectively). The mild inflammation (n = 47) groups had outcomes that were intermediate to the severe inflammation and negative groups (median latency, 7 days; composite morbidity and mortality rates, 53%). In logistic regression adjusting for gestational age at enrollment, IL-6 ≥11.3 and 2.6-11.2 ng/mL, but not MIAC, were associated significantly with composite morbidity and mortality rates (odds ratio [OR], 4.9; 95% confidence interval [CI], 2.2-11.2, OR, 3.1; 95% CI, 1.5-6.4, and OR, 1.8; 95% CI, 0.6-5.5, respectively). CONCLUSION: We confirmed previous reports that intraamniotic inflammation is associated with adverse perinatal outcomes whether or not intraamniotic microbes are detected. Colonization without inflammation appears relatively benign. Intraamniotic inflammation is not simply present or absent but also has degrees of severity that correlate with adverse outcomes. We propose the designation amniotic inflammatory response syndrome to denote the adverse outcomes that are associated with intraamniotic inflammation.

Insurance continuity and human papillomavirus vaccine uptake in Oregon and California federally qualified health centers.

OBJECTIVES: We examined the association between insurance continuity and human papillomavirus (HPV) vaccine uptake in a network of federally qualified health clinics (FQHCs). METHODS: We analyzed retrospective electronic health record data for females, aged 9-26 years in 2008 through 2010. Based on electronic health record insurance coverage information, patients were categorized by percent of time insured during the study period (0%, 1%-32%, 33%-65%, 66%-99%, or 100%). We used bilevel multivariable Poisson regression to compare vaccine-initiation prevalence between insurance groups, stratified by race/ethnicity and age. We also examined vaccine series completion among initiators who had at least 12 months to complete all 3 doses. RESULTS: Significant interactions were observed between insurance category, age, and race/ethnicity. Juxtaposed with their continuously insured peers, patients were less likely to initiate the HPV vaccine if they were insured for less than 66% of the study period, aged 13 years or older, and identified as a racial/ethnic minority. Insurance coverage was not associated with vaccine series completion. CONCLUSIONS: Disparities in vaccine uptake by insurance status were present in the FQHCs studied here, despite the fact that HPV vaccines are available to many patients regardless of ability to pay.

The relationship between 11 different polygenic longevity scores, parental lifespan, and disease diagnosis in the UK Biobank.

Large-scale genome-wide association studies (GWAS) strongly suggest that most traits and diseases have a polygenic component. This observation has motivated the development of disease-specific "polygenic scores (PGS)" that are weighted sums of the effects of disease-associated variants identified from GWAS that correlate with an individual's likelihood of expressing a specific phenotype. Although most GWAS have been pursued on disease traits, leading to the creation of refined "Polygenic Risk Scores" (PRS) that quantify risk to diseases, many GWAS have also been pursued on extreme human longevity, general fitness, health span, and other health-positive traits. These GWAS have discovered many genetic variants seemingly protective from disease and are often different from disease-associated variants (i.e., they are not just alternative alleles at disease-associated loci) and suggest that many health-positive traits also have a polygenic basis. This observation has led to an interest in "polygenic longevity scores (PLS)" that quantify the "risk" or genetic predisposition of an individual towards health. We derived 11 different PLS from 4 different available GWAS on lifespan and then investigated the properties of these PLS using data from the UK Biobank (UKB). Tests of association between the PLS and population structure, parental lifespan, and several cancerous and non-cancerous diseases, including death from COVID-19, were performed. Based on the results of our analyses, we argue that PLS are made up of variants not only robustly associated with parental lifespan, but that also contribute to the genetic architecture of disease susceptibility, morbidity, and mortality.

Prospective cohort study investigating frequency and risk factors for acute pain 1 day after refractive surgery.

BACKGROUND/AIMS: To examine demographic and clinical factors associated with ocular pain 1 day after refractive surgery. METHODS: Prospective study of individuals undergoing refractive surgery. Participants rated their ocular pain on a 0-10 numerical rating scale (NRS) presurgery and 1 day after surgery. Presurgery, participants completed questionnaires on demographics, comorbidities, medications and dry eye and ocular pain symptoms; and an anaesthetised Schirmer test was performed. Acute ocular pain 1 day after surgery was defined as an NRS score of worst pain since surgery ≥3 and this group was compared with individuals with NRS scores<3. RESULTS: 251 individuals underwent refractive surgery (89% laser-assisted in situ keratomileusis, n=222; 11% PRK, n=29). Mean age was 35±8 years (range 19 to 60); 60% (n=150) self-identified as female, 80% (n=203) as White, and 36% (n=89) as Hispanic. Thirteen (5%) individuals reported ocular pain (NRS ≥3) prior to surgery and 67% (n=168) reported ocular pain 1 day after surgery (nine individuals had pain at both time points). Factors that were associated with pain 1 day after surgery included Hispanic ethnicity (adjusted relative risk (aRR) 1.42, 95% CI 1.21 to 1.68, p<0.001) and the presence of eye pain presurgery (aRR 1.10, 95% CI 1.02 to 1.18, p=0.02). CONCLUSION: A majority of individuals report moderate or greater pain within 24 hours of refractive surgery. Hispanic ethnicity and eye pain prior to surgery were associated with self-reported acute postsurgical pain.

Proteomic changes induced by longevity-promoting interventions in mice.

Using mouse models and high-throughput proteomics, we conducted an in-depth analysis of the proteome changes induced in response to seven interventions known to increase mouse lifespan. This included two genetic mutations, a growth hormone receptor knockout (GHRKO mice) and a mutation in the Pit-1 locus (Snell dwarf mice), four drug treatments (rapamycin, acarbose, canagliflozin, and 17α-estradiol), and caloric restriction. Each of the interventions studied induced variable changes in the concentrations of proteins across liver, kidney, and gastrocnemius muscle tissue samples, with the strongest responses in the liver and limited concordance in protein responses across tissues. To the extent that these interventions promote longevity through common biological mechanisms, we anticipated that proteins associated with longevity could be identified by characterizing shared responses across all or multiple interventions. Many of the proteome alterations induced by each intervention were distinct, potentially implicating a variety of biological pathways as being related to lifespan extension. While we found no protein that was affected similarly by every intervention, we identified a set of proteins that responded to multiple interventions. These proteins were functionally diverse but tended to be involved in peroxisomal oxidation and metabolism of fatty acids. These results provide candidate proteins and biological mechanisms related to enhancing longevity that can inform research on therapeutic approaches to promote healthy aging.

Trends and correlates of child passenger restraint use in 6 Northwest tribes: the Native Children Always Ride Safe (Native CARS) project.

OBJECTIVES: We compared proportions of children properly restrained in vehicles in 6 Northwest American Indian tribes in 2003 and 2009, and evaluated risks for improper restraint. METHODS: During spring 2009 we conducted a vehicle observation survey in Oregon, Washington, and Idaho tribal communities. We estimated the proportions of children riding properly restrained and evaluated correlates of improper restraint via log-binomial regression models for clustered data. RESULTS: We observed 1853 children aged 12 years and younger in 1207 vehicles; 49% rode properly restrained. More children aged 8 years and younger rode properly restrained in 2009 than 2003 (51% vs 29%; P < .001). Older booster seat-eligible children were least likely to ride properly restrained in 2009 (25%). American Indian children were more likely to ride improperly restrained than nonnative children in the same communities. Other risk factors included riding with an unrestrained or nonparent driver, riding where child passenger restraint laws were weaker than national guidelines, and taking a short trip. CONCLUSIONS: Although proper restraint has increased, it remains low. Tribe-initiated interventions to improve child passenger restraint use are under way.