Assessing the association of epigenetic age acceleration with osteoarthritis in the Multicenter Osteoarthritis Study (MOST).

PURPOSE: Advancing age is one of the strongest risk factors for osteoarthritis (OA). DNA methylation-based measures of epigenetic age acceleration may provide insights into mechanisms underlying OA. METHODS: We analyzed data from the Multicenter Osteoarthritis Study in a subset of 671 participants ages 45-69 years with no or mild radiographic knee OA. DNA methylation was assessed with the Illumina Infinium MethylationEPIC 850K array. We calculated predicted epigenetic age according to Hannum, Horvath, PhenoAge, and GrimAge epigenetic clocks, then regressed epigenetic age on chronological age to obtain the residuals. Associations between the residuals and knee, hand, and multi-joint OA were assessed using logistic regression, adjusted for chronological age, sex, clinical site, smoking status, and race. RESULTS: Twenty-three percent met criteria for radiographic hand OA, 25% met criteria for radiographic knee OA, and 8% met criteria for multi-joint OA. Mean chronological age (SD) was 58.4 (6.7) years. Mean predicted epigenetic age (SD) according to Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks was 64.9 (6.4), 68.6 (5.9), 50.5 (7.7), and 67.0 (6.2), respectively. Horvath epigenetic age acceleration was not associated with an increased odds of hand OA, odds ratio (95% confidence intervals) = 1.03 (0.99-1.08), with similar findings for knee and multi-joint OA. We found similar magnitudes of associations for Hannum epigenetic age, PhenoAge, and GrimAge acceleration compared to Horvath epigenetic age acceleration. CONCLUSIONS: Epigenetic age acceleration as measured by various well-validated epigenetic clocks based on DNA methylation was not associated with increased risk of knee, hand, or multi-joint OA independent of chronological age.

Phase 1/2a Trial of ISPASM.

BACKGROUND AND PURPOSE: Microthrombosis could play a role in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Tirofiban has shown promising results in reducing delayed cerebral ischemia in retrospective studies. However, the safety of using tirofiban in aneurysmal subarachnoid hemorrhage is not rigorously established. METHODS: A phase 1/2a double-blinded randomized controlled trial (2:1 randomization) to assess the safety of a 7-day intravenous infusion of tirofiban compared with placebo, in patients with aneurysmal subarachnoid hemorrhage treated with ventriculostomy placed in the operative room and coiling was conducted. The primary end point was any intracranial hemorrhage during the hospital stay. The secondary end points were: incidence of radiographic and clinical vasospasm, incidence of delayed cerebral ischemia, and incidence of cerebral ischemic changes noted on magnetic resonance imaging or computed tomography. RESULTS: Eighteen patients received intravenous tirofiban and 12 received placebo. There was no difference in baseline characteristics except for higher male proportions in the tirofiban group. There was no difference in death, in development of new or change in existing intracranial hemorrhages, in thrombocytopenia, and need for shunts in the two arms. However, the tirofiban arm had a lower incidence of delayed cerebral ischemia compared with placebo (6% [1/18] versus 33% [4/12]; P=0.04), and less radiographic vasospasm as detected by catheter angiogram or computed tomography angiography (P=0.01) and computed tomography perfusion (P=0.01). CONCLUSIONS: The above preliminary results support proceeding with further testing of the safety and efficacy of 7-day intravenous infusion of tirofiban in a pragmatic (placing external ventricular drain by the bedside), multicenter setting, and using a larger population. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03691727.

Angiographic Features of Intracranial Aneurysms in Ecuador.

BACKGROUND: Most of the literature describing morphological features of intracranial aneurysms (IAs) is from North-America, East-Asia, and Europe. There is limited data from South-America. We describe the epidemiologic and angiographic features of ruptured and unruptured IAs in a cohort of patients from Ecuador. METHODS: We conducted a retrospective analysis of prospectively acquired databases from 3 different tertiary hospitals over a 3-year period (2014-2017). In a per-patient basis, odd ratios (ORs) of ruptured presentation for each variable using a univariate logistic regression model were calculated. An aneurysm-based multivariate analysis was performed to calculate rupture ORs for each variable. RESULTS: Our sample included 557 patients with 761 IAs. Mean patient age was 52.2 years (range 18-82). Sixty-eight percent were women, and almost 90% presented with ruptured aneurysms and concomitant subarachnoid hemorrhage (SAH). Mean size of all the IAs was 6.4 mm ± 3.98 mm. Most IAs were located in anterior circulation (96.6%): 28.4% medial cerebral artery, 24.4% anterior cerebral artery or anterior communicating artery (ACOM), and 23.5% posterior communicating artery (PCOM). Only 6 basilar tip aneurysms (0.8%) were reported. In the adjusted analysis, aneurysms located in the ACOM (OR 1.89, 95% CI 1.29-2.78) and PCOM (OR 1.84, 95% CI 1.25-2.71), size larger than 5 mm (OR 2.84, 95% CI 2.04-3.93) and 7 mm (OR 2.28, 95% CI 1.64-3.19), and those with non-saccular morphology (OR 9.87, 95% CI 2.21-44.14) were significantly associated with ruptured presentation. CONCLUSIONS: The prevalence of posterior circulation IAs in Ecuador, particularly basilar tip aneurysms, is low when compared to previous reports from developed countries. In our sample, IAs greater than 5 mm (and ≥7 mm) in size, ACOM and PCOM locations, and IAs with nonsaccular morphologies (blister and fusiform) were significantly associated with SAH presentation.

Disparities in Inter-hospital Helicopter Transportation for Hispanics by Geographic Region: A Threat to Fairness in the Era of Thrombectomy.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is a time-dependent therapy that is only available at a limited number of hospitals. As such, patients that live at a considerable distance of those specialized centers often require rapid interhospital emergent evacuation with Helicopter Emergency Medical Services (HEMS) to be considered for MT. It is not known whether the use of HEMS is equitable across different groups of patients. METHODS: Acute ischemic stroke patients emergently transferred to another facility were identified in a retrospective review of a large Medicare claims database. Mode of transportation (HEMS, advanced, or basic ground ambulances) was determined by CPT codes. Distance from patient's residence to the closest center with MT capabilities was calculated. Generalized linear mixed logit models were used to determine the odds of HEMS relative to ground services for Hispanic and non-Hispanic black (NHB) patients relative to non-Hispanic white (NHW) patients while controlling for confounders. RESULTS: A total of 8027 patients that underwent emergent interhospital transportation were analyzed. HEMS utilization was 18.1% for NHB, 20.6% for Hispanics, and 21.6% for NHW (P = .054). In adjusted analyses for confounders, including distance to a MT-capable hospital, Hispanic patients were less likely than NHWs to be transported by HEMS. While that association had marginal significance for the whole United States (OR = .76; 95% CI, .57-1.01; P = .055), it was statistically significant for patients living in the southern region of the United States (OR = .6; 95% CI, .40-.92; P = .019). DISCUSSION: Our findings suggest there is a disparity in the use of HEMS in Hispanic stroke patients compared to NHW. Such a disparity may delay arrival to a MT-capable hospital, delay treatment times, or lead to ineligibility for MT altogether. Given the known benefit of MT and known existing disparities in stroke treatment and outcomes, it is important to further investigate and address disparities in mode of interhospital transportation.

Intravenous immune globulin and thromboembolic adverse events in patients with hematologic malignancy.

In patients with hypogammaglobulinemia secondary to chronic lymphocytic leukemia (CLL) or multiple myeloma (MM), intravenous immune globulin (IVIg) may be administered to reduce the risk of infection. Since 2013, IVIg products have carried a boxed safety warning about the risk of thromboembolic events (TEEs), with TEEs reported in 0.5% to 15% of patients treated with IVIg. In this retrospective cohort study of older patients with CLL or MM identified from the Surveillance, Epidemiology, and End Results-Medicare Linked Database, we assessed rates of clinically serious TEEs in 2724 new users of IVIg and a propensity-matched comparison group of 8035 nonusers. For the primary end point, arterial TEE, we observed a transient increased risk of TEE during the day of an IVIg infusion and the day afterward (hazard ration = 3.40; 95% confidence interval [CI]: 1.25, 9.25); this risk declined over the remainder of the 30-day treatment cycle. When considered in terms of absolute risk averaged over a 1-year treatment period, the increase in risk attributable to IVIg was estimated to be 0.7% (95% CI: -0.2%, 2.0%) compared with a baseline risk of 1.8% for the arterial TEE end point. A statistically nonsignificant risk increase of 0.3% (95% CI: -0.4%, 1.5%) compared with a baseline risk of 1.1% was observed for the venous TEE end point. Further research is needed to establish the generalizability of these results to patients receiving higher doses of IVIg for other indications.

Emergency department charges may be associated with mortality in patients with severe sepsis and septic shock: a cohort study.

BACKGROUND: Sepsis severity of illness is challenging to measure using claims, which makes sepsis difficult to study using administrative data. We hypothesized that emergency department (ED) charges may be associated with hospital mortality, and could be a surrogate marker of severity of illness for research purposes. The objective of this study was to measure concordance between ED charges and mortality in admitted patients with severe sepsis or septic shock. METHODS: Cohort study of all adult patients presenting to a 60,000-visit Midwestern academic ED with severe sepsis or septic shock (by ICD-9 codes) between July 1, 2008 and June 30, 2010. Data on demographics, admission APACHE-II score, and disposition was extracted from the medical record, and comorbidities were identified from diagnosis codes using the Elixhauser methodology. Summary statistics were reported and bivariate concordance was tested using Pearson correlation. Logistic regression models for 28-day mortality were developed to measure the independent association with mortality. RESULTS: We included a total of 294 patients in the analysis. We found that ED charges were inversely related to mortality (adjusted OR 0.829 per $1000 increase in total ED charges, 95%CI 0.702-0.980). ED charges were also independently associated with 28-day hospital-free and ICU-free days (0.74 days increase per $1000 additional ED charges, 95%CI 0.06-1.41 and 0.81 days increase per $1000 additional ED charges, 95%CI 0.05-1.56, respectively). ED charges were also associated with APACHE-II score ($34 total ED charges per point increase in APACHE-II score, 95%CI $6-62). CONCLUSIONS: ED charges in administrative data sets are associated with in-hospital mortality and health care utilization, likely related to both illness severity and intensity of early sepsis resuscitation. ED charges may have a role in risk adjustment models using administrative data for acute care research.

Management of Brain Arteriovenous Malformations: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association.

PURPOSE: The aim of this statement is to review the current data and to make suggestions for the diagnosis and management of both ruptured and unruptured brain arteriovenous malformations. METHODS: The writing group met in person and by teleconference to establish search terms and to discuss narrative text and suggestions. Authors performed their own literature searches of PubMed, Medline, or Embase, specific to their allocated section, through the end of January 2015. Prerelease review of the draft statement was performed by expert peer reviewers and by the members of the Stroke Council Scientific Oversight Committee and Stroke Council Leadership Committee. RESULTS: The focus of the scientific statement was subdivided into epidemiology; diagnosis; natural history; treatment, including the roles of surgery, stereotactic radiosurgery, and embolization; and management of ruptured and unruptured brain arteriovenous malformations. Areas requiring more evidence were identified. CONCLUSIONS: Brain arteriovenous malformations are a relatively uncommon but important cause of hemorrhagic stroke, especially in young adults. This statement describes the current knowledge of the natural history and treatment of patients with ruptured and unruptured brain arteriovenous malformations, suggestions for management, and implications for future research.

Relationship of Trochlear Morphology and Patellofemoral Joint Alignment to Superolateral Hoffa Fat Pad Edema on MR Images in Individuals with or at Risk for Osteoarthritis of the Knee: The MOST Study.

Purpose To determine the relationship of patellofemoral joint alignment and trochlear morphology to superolateral Hoffa fat pad (SHFP) edema on magnetic resonance (MR) images in older adults with or at risk for osteoarthritis of the knee. Materials and Methods Institutional review board approval and written informed consent were obtained from all subjects. The Multicenter Osteoarthritis Study is a prospective cohort study of older adults with or at risk for osteoarthritis of the knee. Subjects were recruited from Birmingham, Alabama, and Iowa City, Iowa. In this cross-sectional study, patellofemoral joint alignment (bisect offset, patellar tilt angle, and Insall-Salvati ratio), trochlear morphology (sulcus angle, lateral and medial trochlear inclination, and trochlear angle) and SHFP edema were assessed on MR images of the knee. Measures of alignment and morphology were divided into quartiles, and SHFP was determined to be present or absent. Separate logistic regression models were used to determine the relationship of each measure of alignment and morphology to the presence of SHFP edema, with adjustments for age, sex, and body mass index. Results SHFP edema was present in 152 (13.4%) of the 1134 knees that were included. When compared with knees with measurements in the lowest quartile, knees with measurements in the highest quartile for trochlear angle, bisect offset, and Insall-Salvati ratios were 1.6 (95% confidence interval [CI]: 1.0, 2.6), 2.3 (95% CI: 1.3, 4.0), and 8.9 (95% CI: 4.7, 16.9) times more likely to show SHFP edema, respectively. No relationship was found between other measures and SHFP edema. Conclusion A more anterior trochlear facet, a more laterally displaced patella, and knees with patella alta were significantly associated with SHFP edema on MR images in subjects with or at risk for osteoarthritis of the knee. © RSNA, 2017.

Rural Patients With Severe Sepsis or Septic Shock Who Bypass Rural Hospitals Have Increased Mortality: An Instrumental Variables Approach.

OBJECTIVE: To identify factors associated with rural sepsis patients' bypassing rural emergency departments to seek emergency care in larger hospitals, and to measure the association between rural hospital bypass and sepsis survival. DESIGN: Observational cohort study. SETTING: Emergency departments of a rural Midwestern state. PATIENTS: All adults treated with severe sepsis or septic shock between 2005 and 2014, using administrative claims data. INTERVENTIONS: Patients bypassing local rural hospitals to seek care in larger hospitals. MEASUREMENTS AND MAIN RESULTS: A total of 13,461 patients were included, and only 5.4% (n = 731) bypassed a rural hospital for their emergency department care. Patients who initially chose a top-decile sepsis volume hospital were younger (64.7 vs 72.7 yr; p < 0.001) and were more likely to have commercial insurance (19.6% vs 10.6%; p < 0.001) than those who were seen initially at a local rural hospital. They were also more likely to have significant medical comorbidities, such as liver failure (9.9% vs 4.2%; p < 0.001), metastatic cancer (5.9% vs 3.2%; p < 0.001), and diabetes with complications (25.2% vs 21.6%; p = 0.024). Using an instrumental variables approach, rural hospital bypass was associated with a 5.6% increase (95% CI, 2.2-8.9%) in mortality. CONCLUSIONS: Most rural patients with sepsis seek care in local emergency departments, but demographic and disease-oriented factors are associated with rural hospital bypass. Rural hospital bypass is independently associated with increased mortality.

Longitudinal associations between mental health conditions and overactive bladder in women veterans.

BACKGROUND: One in 5 recently deployed US women veterans report overactive bladder symptoms. Mental health conditions such as depression and anxiety commonly co-occur in women with overactive bladder, but temporal relationships between these outcomes have not been well studied, and the mechanism behind this association is unknown. The Women Veterans Urinary Health Study, a nationwide longitudinal study in recently deployed women veterans, was designed to better understand relationships between overactive bladder and mental health conditions. OBJECTIVE: We sought to estimate the 1-year incidence and remission of overactive bladder and to identify the impact of depression, anxiety, posttraumatic stress disorder, and prior sexual assault on 1-year overactive bladder incidence and remission rates. STUDY DESIGN: Participants of this 1-year prospective cohort study were female veterans separated from military service who had returned from Iraq or Afghanistan deployment within the previous 2 years. Eligible women were identified through the Defense Manpower Data Center and recruited by mail and telephone. Telephone screening confirmed participants were ambulatory, community-dwelling veterans and excluded those with urinary tract fistula, congenital abnormality, or cancer; pelvic radiation; spinal cord injury; multiple sclerosis; Parkinson disease; stroke; or current/recent pregnancy. Data collection included computer-assisted telephone interviews performed at enrollment and 1 year later. The interview assessed demographic and military service characteristics; urinary symptoms and treatment; depression, anxiety, and posttraumatic stress disorder symptoms and treatment; and a lifetime history of sexual assault. Overactive bladder was identified if at least moderately bothersome urgency urinary incontinence and/or urinary frequency symptoms were reported on Urogenital Distress Inventory items. Exposures included depression, anxiety, posttraumatic stress disorder, and lifetime sexual assault, assessed at baseline using validated questionnaires (including the Patient Health Questionnaire and Posttraumatic Stress Disorder Checklist). Associations between exposures and overactive bladder incidence and remission were estimated using propensity score adjusted logistic regression models. RESULTS: In all, 1107 (88.0%) of 1258 eligible participants completed 1-year interviews. Median age was 29 (range 20-67) years and 53% were nulliparous. Overactive bladder was identified at baseline in 242 (22%), and 102 (9.2%), 218 (19.7%), 188 (17.0%), and 287 (25.9%) met criteria for baseline depression, anxiety, posttraumatic stress disorder, and lifetime sexual assault, respectively. At 1 year, overactive bladder incidence was 10.5% (95% confidence interval, 8.6-12.8%), and remission of overactive bladder was 36.9% (95% confidence interval, 30.8-43.4%). New overactive bladder occurred more often in women with baseline anxiety (21% vs 9%), posttraumatic stress disorder (19% vs 9%) and lifetime sexual assault (16% vs 9%) (all: P < .01). After adjustment, anxiety (odds ratio, 2.4; 95% confidence interval, 1.4-4.1) and lifetime sexual assault (odds ratio, 1.7; 95% confidence interval, 1.0-2.8) predicted 1-year incident overactive bladder. Overactive bladder remission occurred less often in those with baseline depression (19% vs 41%, P < .01) and anxiety (29% vs 42%, P = .03). After adjustment, depression decreased 1-year overactive bladder remission risk (odds ratio, 0.37; 95% confidence interval, 0.16-0.83). Overactive bladder treatment was uncommon and not associated with remission. CONCLUSION: Anxiety, depression, and prior sexual assault-common postdeployment problems for women veterans-influence the natural history of overactive bladder. Providers should screen for mental health conditions and sexual assault in women with newly diagnosed or persistent overactive bladder.

The Relationship Between US Military Officer Leadership Behaviors and Risk of Sexual Assault of Reserve, National Guard, and Active Component Servicewomen in Nondeployed Locations.

OBJECTIVES: To determine if military leader behaviors are associated with active component and Reserve-National Guard servicewomen's risk of sexual assault in the military (SAIM) for nondeployed locations. METHODS: A community sample of 1337 Operation Enduring Freedom and Operation Iraqi Freedom-era Army and Air Force servicewomen completed telephone interviews (March 2010-December 2011) querying sociodemographic and military characteristics, sexual assault histories, and leader behaviors. We created 2 factor scores (commissioned and noncommissioned) to summarize behaviors by officer rank. RESULTS: A total of 177 servicewomen (13%) experienced SAIM in nondeployed locations. Negative leader behaviors were associated with increased assault risk, at least doubling servicewomen's odds of SAIM (e.g., noncommissioned officers allowed others in unit to make sexually demeaning comments; odds ratio = 2.7; 95% confidence interval = 1.8, 4.1). Leader behavior frequencies were similar, regardless of service type. Negative leadership behavior risk factors remained significantly associated with SAIM risk even after adjustment for competing risk. Noncommissioned and commissioned officer factor scores were highly correlated (r = 0.849). CONCLUSIONS: The association between leader behaviors and SAIM indicates that US military leaders have a critical role in influencing servicewomen's risk of and safety from SAIM.

Sexual assault in the US military: A comparison of risk in deployed and non-deployed locations among Operation Enduring Freedom/Operation Iraqi Freedom active component and Reserve/National Guard servicewomen.

BACKGROUND: To determine whether sexual assault in the military (SAIM) among active component and Reserve/National Guard servicewomen is more likely to occur in deployed or non-deployed locations; and which location poses greater risk for SAIM when time spent in-location is considered. METHODS: A total of 1337 Operation Enduring Freedom/Operation Iraqi Freedom era servicewomen completed telephone interviews eliciting socio-demographics, military and sexual assault histories, including attempted and completed sexual assault. RESULTS: Half of the sample had been deployed (58%). Overall 16% (N = 245) experienced SAIM; a higher proportion while not deployed (15%; n = 208) than while deployed (4%; n = 52). However, the incidence of SAIM per 100 person-years was higher in deployed than in non-deployed locations: 3.5 vs 2.4. Active component and Reserve/National Guard had similar deployment lengths, but Reserve/National Guard had higher SAIM incidence rates/100 person-years (2.8 vs 4.0). CONCLUSIONS: A higher proportion of servicewomen experienced SAIM while not deployed; however, adjusting for time in each location, servicewomen were at greater risk during deployment.

Hysterectomy risk in premenopausal-aged military veterans: associations with sexual assault and gynecologic symptoms.

BACKGROUND: Several gynecological conditions associated with hysterectomy, including abnormal bleeding and pelvic pain, have been observed at increased rates in women who have experienced sexual assault. Previous findings have suggested that one of the unique health care needs for female military veterans may be an increased prevalence of hysterectomy and that this increase may partially be due to their higher risk of sexual assault history and posttraumatic stress disorder (PTSD). Although associations between trauma, PTSD, and gynecological symptoms have been identified, little work has been done to date to directly examine the relationship between sexual assault, PTSD, and hysterectomy within the rapidly growing female veteran population. OBJECTIVES: The objective of the study was to assess the prevalence of hysterectomy in premenopausal-aged female veterans, compare with general population prevalence, and examine associations between hysterectomy and sexual assault, PTSD, and gynecological symptoms in this veteran population. STUDY DESIGN: We performed a computer-assisted telephone interview between July 2005 and August 2008 of 1004 female Veterans Affairs (VA)-enrolled veterans ≤ 52 years old from 2 Midwestern US Veterans Affairs medical centers and associated community-based outreach clinics. Within the veteran study population, associations between hysterectomy and sexual assault, PTSD, and gynecological symptoms were assessed with bivariate analyses using χ(2), Wilcoxon-Mann-Whitney, and Student t tests; multivariate logistic regression analyses were used to look for independent associations. Hysterectomy prevalence and ages were compared with large civilian populations represented in the Behavioral Risk Factor Surveillance System and American College of Surgeons National Surgical Quality Improvement Program databases from similar timeframes using χ(2) and Student t tests. RESULTS: Prevalence of hysterectomy was significantly higher (16.8% vs 13.3%, P = .0002), and mean age at hysterectomy was significantly lower (35 vs 43 years old, P < .0001) in this VA-enrolled sample of female veterans compared with civilian population-based data sets. Sixty-two percent of subjects had experienced attempted or completed sexual assault in their lifetimes. A history of completed lifetime sexual assault with vaginal penetration (LSA-V) was a significant risk factor for hysterectomy (age-adjusted odds ratio, 1.85), with those experiencing their first LSA-V in childhood or in military at particular risk. A history of PTSD was also associated with hysterectomy (age-adjusted odds ratio, 1.83), even when controlling for LSA-V. These associations were no longer significant when controlling for the increased rates of gynecological pain, abnormal gynecological bleeding, and pelvic inflammatory disease seen in those veterans with a history of LSA-V. CONCLUSION: Premenopausal-aged veterans may be at higher overall risk for hysterectomy, and for hysterectomy at younger ages, than their civilian counterparts. Veterans who have experienced completed sexual assault with vaginal penetration in childhood or in military and those with a history of PTSD may be at particularly high risk for hysterectomy, potentially related to their higher risk of gynecological symptoms. If confirmed in future studies, these findings have important implications for women's health care providers and policy makers within both the VA and civilian health care systems related to primary and secondary prevention, costs, and the potential for increased chronic disease and mortality.

Intravenous immune globulin and thromboembolic adverse events: A systematic review and meta-analysis of RCTs.

Prior case reports and observational studies indicate that intravenous immune globulin (IVIg) products may cause thromboembolic events (TEEs), leading the FDA to require a boxed warning in 2013. The effect of IVIg treatment on the risk of serious TEEs (acute myocardial infarction, ischemic stroke, or venous thromboembolism) was assessed using adverse event data reported in randomized controlled trials (RCTs) of IVIg. RCTs of IVIg in adult patients from 1995 to 2015 were identified from Pubmed, Embase, ClinicalTrials.Gov, and two large prior reviews of IVIg's therapeutic applications. Trials at high risk of detection or reporting bias for serious adverse events were excluded. 31 RCTs with a total of 4,129 participants (2,318 IVIg-treated, 1,811 control) were eligible for quantitative synthesis. No evidence was found of increased TEE risk among IVIg-treated patients compared with control patients (odds ratio = 1.10, 95% CI: 0.44, 2.88; risk difference = 0.0%, 95% CI: -0.7%, 0.7%, I(2) = 0%). No significant increase in risk was found when arterial and venous TEEs were analyzed as separate endpoints. Trial publications provided little specific information concerning the methods used to ascertain potential adverse events. Care should be taken in extrapolating the results to patients with higher baseline risks of TEE. Am. J. Hematol. 91:594-605, 2016. © 2016 Wiley Periodicals, Inc.

Post-sexual assault health care utilization among OEF/OIF servicewomen.

BACKGROUND AND OBJECTIVES: Few who experience sexual assault seek health care immediately. Yet many become heavy users of health care resources in the years postassault because sexual violence has been linked with both acute and chronic health consequences. Our objective was to investigate servicewomen's medical and mental health (MH) care utilization after sexual assault in-military (SAIM) and identify reasons for not seeking care. METHODS: In a retrospective cross-sectional Midwestern community sample of OEF/OIF Active Component and Reserve/National Guard servicewomen, currently serving and veterans, computer-assisted telephone interviews were conducted with 207 servicewomen who experienced SAIM. RESULTS: A quarter (25%) received post-SAIM MH care and 16% medical care. Utilization of medical care tended to be sooner (within the first month) and MH care later (6 mo to 1+ y). Most sought care on a military base, a third from civilian providers, and 10% sought MH from Veterans Health Administration. Servicewomen were more likely to have utilized medical care if they had experienced a completed SAIM and made a Department of Defense SAIM report and MH care if they were white, experienced on-duty SAIM, and made a Department of Defense SAIM report. The most common reason for not seeking medical care was due to belief that care was not needed. Reasons for not utilizing medical or MH care included embarrassment, confidentiality concerns, and fear of adverse career consequences. CONCLUSIONS: Few servicewomen utilized post-SAIM care, thus assault-specific health consequences were likely unaddressed. Given the severe and chronic consequences of sexual assault, our findings emphasize need for military, Veterans Health Administration, and civilian providers to query SAIM history to provide timely and optimal care.

Prevalence and correlates of cigarette smoking among operation Iraqi freedom-era and operation enduring freedom-era women from the Active Component military and Reserve/National Guard.

BACKGROUND: Tobacco use adversely affects the health and readiness of military personnel. Although rates of cigarette smoking have historically been elevated among men serving in the military, less is known about tobacco use in servicewomen. OBJECTIVES: To examine the prevalence and correlates of tobacco use among women serving in the Active Component (AC) and Reserve/National Guard (RNG) as well as factors associated with starting to smoke during military service. METHODS: Cross-sectional surveys of 1320 women serving in the AC or RNG were used to examine cigarette use in servicewomen. Associations between self-reported tobacco use history, sociodemographics, military service, and psychosocial factors were investigated using logistic regression analyses. RESULTS: Thirty-six percent of servicewomen had a lifetime history of cigarette use, with 18% reporting current smoking. Thirty-one percent of lifetime smokers initiated smoking during military service. Factors associated with current smoking included pay grade, marital status, use of psychotropic medications, past-year alcohol use, and lifetime illicit drug or illegal prescription medication use. An enlisted pay grade, being white, and a history of deployment were all associated with starting to smoke during military service. CONCLUSIONS: Although progress has been made in reducing the gap in tobacco use between military and civilian populations, nearly 1 in 5 servicewomen in our sample smoked cigarettes. Further efforts are needed to address tobacco use in this population. In addition to providing resources to assist smokers with quitting, additional attention should be given to preventing smoking initiation, particularly among deployed female personnel.

Age of collagen in intracranial saccular aneurysms.

BACKGROUND AND PURPOSE: The chronological development and natural history of cerebral aneurysms (CAs) remain incompletely understood. We used (14)C birth dating of a main constituent of CAs, that is, collagen type I, as an indicator for biosynthesis and turnover of collagen in CAs in relation to human cerebral arteries to investigate this further. METHODS: Forty-six ruptured and unruptured CA samples from 43 patients and 10 cadaveric human cerebral arteries were obtained. The age of collagen, extracted and purified from excised CAs, was estimated using (14)C birth dating and correlated with CA and patient characteristics, including the history of risk factors associated with atherosclerosis and potentially aneurysm growth and rupture. RESULTS: Nearly all CA samples contained collagen type I, which was <5 years old, irrespective of patient age, aneurysm size, morphology, or rupture status. However, CAs from patients with a history of risk factors (smoking or hypertension) contained significantly younger collagen than CAs from patients with no risk factors (mean, 1.6±1.2 versus 3.9±3.3 years, respectively; P=0.012). CAs and cerebral arteries did not share a dominant structural protein, such as collagen type I, which would allow comparison of their collagen turnover. CONCLUSIONS: The abundant amount of relatively young collagen type I in CAs suggests that there is an ongoing collagen remodeling in aneurysms, which is significantly more rapid in patients with risk factors. These findings challenge the concept that CAs are present for decades and that they undergo only sporadic episodes of structural change.

Multidisciplinary consensus on assessment of unruptured intracranial aneurysms: proposal of an international research group.

BACKGROUND AND PURPOSE: To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. METHODS: After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. RESULTS: Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. CONCLUSIONS: Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.

Overactive bladder and mental health symptoms in recently deployed female veterans.

PURPOSE: We estimate the prevalence of current overactive bladder symptoms in recently deployed female veterans, and determine if overactive bladder symptoms are associated with problems commonly reported after deployment including mental health symptoms and prior sexual assault. MATERIALS AND METHODS: Baseline data were analyzed from a nationwide cohort study of urogenital symptoms in female veterans. Women returning from deployment to Iraq or Afghanistan in the prior 2 years and ending military service were eligible. Self-reported data were collected by computer assisted telephone interview. Overactive bladder and mental health conditions were identified using standardized definitions as well as validated urinary and mental health instruments. Associations between overactive bladder and depression, post-traumatic stress disorder, anxiety and sexual assault were assessed in separate logistic regression models using propensity scores to adjust for confounding. RESULTS: The 1,702 participants had a mean (SD) age of 31.1 (8.4) years and were racially/ethnically diverse. Overall 375 participants (22%; 95% CI 20.1, 24.1) reported overactive bladder. Mental health outcomes included post-traumatic stress disorder (19%), anxiety (21%), depression (10%) and prior sexual assault (27%). All outcomes were associated with overactive bladder (adjusted OR 2.7, 95% CI [2.0, 3.6], 2.7 [2.0, 3.5], 2.5 [1.5, 4.3] and 1.4 [1.1, 1.9], respectively). CONCLUSIONS: Overactive bladder symptoms occurred in 22% of recently deployed female veterans, and were associated with self-reported mental health symptoms and traumatic events including prior sexual assault. Screening and evaluation for bothersome urinary symptoms and mental health problems appear warranted in female veterans presenting for primary and urological care after deployment.

Objectively measured physical activity trajectories predict adolescent bone strength: Iowa Bone Development Study.

BACKGROUND: Physical activity improves bone strength and reduces the risk for osteoporotic fractures. However, there are substantial gaps in our knowledge as to when, how and how much activity is optimal for bone health. PURPOSE: In this cohort study, we examined developmental trajectories of objectively measured physical activity from childhood to adolescence to discern if moderate-and-vigorous intensity physical activity (MVPA) predicts bone strength. METHODS: Starting at age 5 and continuing at 8, 11, 13, 15 and 17 years, Iowa Bone Development Study participants (n=530) wore an accelerometer for 3-5 days. At age 17, we assessed dual X-ray energy absorptiometry outcomes of mass and estimated geometry (femoral neck cross-sectional area and section modulus). We also assessed geometric properties (bone stress index and polar moment of inertia) of the tibia using peripheral computer quantitative tomography. Latent class modelling was used to construct developmental trajectories of MVPA from childhood to late adolescence. General linear models were used to examine the trajectory groups as predictors of age 17 bone outcomes. RESULTS: Girls and boys who accumulated the most MVPA had greater bone mass and better geometry at 17 years when compared to less active peers. The proportion of participants achieving high levels of MVPA throughout childhood was very low (<6% in girls) and by late adolescence almost all girls were inactive. CONCLUSIONS: Bone health benefits of physical activity are not being realised due to low levels of activity for most youth, especially in girls.