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.

Dietary omega-6/omega-3 fatty acids and risk of prostate cancer; Is there any potential interaction by organophosphate insecticides among the agricultural health study population.

BACKGROUND: In the United States (US), the average annual increase in the incidence of prostate cancer (PCa) has been 0.5% between 2013 and 2017. Although some modifiable factors have been identified as the risk factors for PCa, the effect of lower ratio of omega-6 to omega-3 fatty acids intake (N-6/N-3) remains unknown. Previous studies of the Agricultural Health Study (AHS) reported a significant positive association between PCa and selected organophosphate pesticides (OPs) including terbufos and fonofos. OBJECTIVE: The aim of this study was to evaluate the association between N-6/N-3 and PCa and any interaction between N-6/N-3 and 2 selected OPs (i.e., terbufos and fonofos) exposure. DESIGN AND PARTICIPANTS: This case-control study, nested within a prospective cohort study, was conducted on a subgroup of the AHS population (1193 PCa cases and 14,872 controls) who returned their dietary questionnaire between 1999 and 2003 MAIN OUTCOME MEASURES: PCa was coded based on the International Classification of Diseases of Oncology (ICD-O-3) definitions and obtained from the statewide cancer registries of Iowa (2003-2017) and North Carolina (2003-2014). STATISTICAL ANALYSIS: Multivariate logistic regression analysis was applied to obtain the odds ratios adjusted (aORs) for age at dietary assessment (years), race/ethnicity (white, African American, other), physical activity (hours/week), smoking (yes/no), terbufos (yes/no), fonofos (yes/no), diabetes, lycopene intake (milligrams/day), family history of PCa, and the interaction of N-6/N-3 with age, terbufos and fonofos. Pesticide exposure was assessed by self-administrated questionnaires collecting data on ever/never use of mentioned pesticides during lifetime as a yes/no variable. Assessing the P value for the interaction between pesticides and N-6/N-3, we used the continuous variable of "intensity adjusted cumulative exposure" to terbufos and fonofos. This exposure score was based on duration, intensity and frequency of exposure. We also conducted a stratified regression analysis by quartiles of age. RESULTS: Relative to the highest N-6/N-3 quartile, the lowest quartile was significantly associated with a decreased risk of PCa (aOR=0.61, 95% CI: 0.41-0.90), and quartile-specific aORs decreased toward the lowest quartile (Ptrend=<0.01). Based on the age-stratified analysis, the protective effect was only significant for the lowest quartile of N-6/N-3 among those aged between 48 and 55 years old (aORs=0.97, 95% CI, 0.45-0.55). Among those who were exposed to terbufos (ever exposure reported as yes in the self-report questionnaires), lower quartiles of N-6/N-3 were protective albeit nonsignificant (aORs: 0.86, 0.92, 0.91 in quartiles 1,2, and 3, respectively). No meaningful findings were observed for fonofos and N-6/N-3 interaction. CONCLUSION: Findings showed that lower N-6/N-3 may decrease risk of PCa among farmers. However, no significant interaction was found between selected organophosphate pesticides and N-6/N-3.

Do associations with hand OA vary by knee osteoarthritis phenotype? Cross-sectional data from the Multicenter Osteoarthritis Study.

Objective: Osteoarthritis (OA) is highly heterogeneous and has both biomechanical and systemic components that may not have the same etiology. We therefore aimed to identify specific knee OA phenotypes that may be more strongly associated with hand OA to refine the criteria used to define multi-joint OA. Design: We assessed data from the Multicenter Osteoarthritis Study (MOST). We ascertained hand OA from bilateral hand photographs; scores for each joint row were summed to yield an aggregate hand OA score. Knee OA was ascertained from bilateral posteroanterior knee radiographs read for Kellgren-Lawrence grade and individual radiographic features. We tested associations between hand and knee OA with phenotypes including symptomatic OA, hyper- and atrophic knee OA, and one excluding post-traumatic OA. Associations between hand and knee OA were assessed with logistic regression, adjusted for age. Results: We studied 2493 participants with hand and knee OA measures. Median age was 63 years with 57% women. 55% had an aggregate hand OA score ≥2; frequency of knee OA phenotypes ranged from 8% to 34%. The age-adjusted odds ratio (OR) was 1.14 (95% confidence interval (CI) â€‹= â€‹1.04-1.26) for knee OA per standard deviation of the hand OA aggregate score. Hand OA associations with symptomatic knee OA and knee OA excluding post-traumatic knee OA were OR â€‹= â€‹1.16 (95% CI â€‹= â€‹1.03-1.31) and OR â€‹= â€‹1.21 (95% CI â€‹= â€‹1.08-1.35), respectively. No other knee OA phenotype reached statistical significance. Conclusions: Age-adjusted associations between hand and knee OA were modest and were largely similar across knee OA phenotypes.

Relation of Temporal Asymmetry During Walking to Two-Year Knee Pain Outcomes in Those With Mild-to-Moderate Unilateral Knee Pain: An Exploratory Analysis From the Multicenter Osteoarthritis Study.

OBJECTIVE: We aimed to explore the cross-sectional relation of unilateral knee pain severity and temporal asymmetry during walking and to determine relations of temporal asymmetry during walking to 2-year changes in ipsilateral and contralateral knee pain in those with mild-to-moderate unilateral knee pain. METHODS: The Multicenter Osteoarthritis Study is a prospective cohort study of adults with or at risk for knee osteoarthritis. The current study included participants with unilateral knee pain. Gait was assessed during self-selected and fast walking at baseline. Knee pain was assessed at baseline and 2 years. We calculated limb symmetry indices (LSIs; nonpainful limb/painful limb × 100) for stance, single-limb support time, and double-limb support time, then examined their relations to unilateral knee pain severity, incident contralateral knee pain, and persistent ipsilateral knee pain. RESULTS: Unilateral knee pain severity was not associated with temporal asymmetry during self-selected or fast walking. At 2 years, 17.1% of participants had incident contralateral knee pain and 51.4% had persistent ipsilateral knee pain. For self-selected walking, greater LSIs (i.e., longer time on the nonpainful limb) for stance and single-limb support time were associated with decreased odds of incident contralateral knee pain. Measures of temporal asymmetry were not associated with persistent ipsilateral knee pain, except for single-limb support time during fast walking. CONCLUSION: For those with unilateral knee pain, temporal asymmetry during walking is not associated with pain severity. However, select measures of stance and single-limb support time during self-selected and fast walking relate to longitudinal knee pain outcomes.

Online Screening and Personalized Education to Identify Post-Deployment Mental Health Need and Facilitate Access to Care.

INTRODUCTION: Reserve and National Guard (RNG) service members face increased risks for psychological and behavioral problems and are unlikely to seek mental health (MH) care after returning from military deployments. This article examines an online intervention (Web-Ed) with regard to participation, screening results, satisfaction, and intent to seek follow-up MH care, with comparisons by gender and post-deployment MH care receipt. MATERIALS AND METHODS: This was a cross-sectional study of 414 RNG service members (214 women and 200 men), who returned from deployments to or in support of the Iraq or Afghanistan wars within the prior 36 months. Participants completed Web-Ed, which includes screening, personalized education, and links to Veterans Health Administration health care. RESULTS: Positive post-deployment screening proportions, Web-Ed satisfaction, and intent to seek follow-up care were similar for men and women. Few had received MH care (33% women; 24% men), yet most screened positive on at least one screen (69% women; 72% men). Most indicated that they would recommend Web-Ed to other veterans (71% women; 67% men) and that they received useful information they may not have received otherwise (52% women; 53% men) regardless of gender or prior MH care. Almost half (40% women; 48% men) planned to seek further assessment from a health care provider as a direct result of Web-Ed. CONCLUSIONS: Efforts to facilitate access to MH care among post-deployed RNG veterans should be ongoing, regardless of the length of time since deployment, Veterans Affairs enrollment status, prior MH care receipt, or gender. Online screening and personalized education engage veterans who have not sought MH care and provide new information to those who have.

Computed Tomography-Based Stiffness Measures of Trabecular Bone Microstructure: Cadaveric Validation and In Vivo Application.

Osteoporosis causes bone fragility and elevates fracture risk. Applications of finite element (FE) analysis (FEA) for assessment of trabecular bone (Tb) microstructural strength at whole-body computed tomography (CT) imaging are limited due to challenges with Tb microstructural segmentation. We present a nonlinear FEA method for distal tibia CT scans evading binary segmentation of Tb microstructure, while accounting for bone microstructural distribution. First, the tibial axis in a CT scan was aligned with the FE loading axis. FE cubic mesh elements were modeled using image voxels, and CT intensity values were calibrated to ash density defining mechanical properties at individual elements. For FEA of an upright volume of interest (VOI), the bottom surface was fixed, and a constant displacement was applied at each vertex on the top surface simulating different loading conditions. The method was implemented and optimized using the ANSYS software. CT-derived computational modulus values were repeat scan reproducible (intraclass correlation coefficient [ICC] ≥ 0.97) and highly correlated (r ≥ 0.86) with the micro-CT (µCT)-derived values. FEA-derived von Mises stresses over the segmented Tb microregion were significantly higher (p < 1 × 10-11) than that over the marrow space. In vivo results showed that both shear and compressive modulus for males were higher (p < 0.01) than for females. Effect sizes for different modulus measures between males and females were moderate-to-high (≥0.55) and reduced to small-to-negligible (<0.40) when adjusted for pure lean mass. Among body size and composition attributes, pure lean mass and height showed highest (r ∈ [0.45 0.56]) and lowest (r ∈ [0.25 0.39]) linear correlation, respectively, with FE-derived modulus measures. In summary, CT-based nonlinear FEA provides an effective surrogate measure of Tb microstructural stiffness, and the relaxation of binary segmentation will extend the scope for FEA in human studies using in vivo imaging at relatively low-resolution. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Magnetic Resonance Imaging-Defined Osteoarthritis Features and Anterior Knee Pain in Individuals With, or at Risk for, Knee Osteoarthritis: A Multicenter Study on Osteoarthritis.

OBJECTIVE: The lack of strong association between knee osteoarthritis (OA) structural features and pain continues to perplex researchers and clinicians. Evaluating the patellofemoral joint in addition to the tibiofemoral joint alone has contributed to explaining this structure-pain discordance, hence justifying a more comprehensive evaluation of whole-knee OA and pain. The present study, therefore, was undertaken to evaluate the association between patellofemoral and tibiofemoral OA features with localized anterior knee pain (AKP) using 2 study designs. METHODS: Using cross-sectional data from the Multicenter Osteoarthritis Study, our first approach was a within-person, knee-matched design in which we identified participants with unilateral AKP. We then assessed magnetic resonance imaging (MRI)-derived OA features (cartilage damage, bone marrow lesions [BMLs], osteophytes, and inflammation) in both knees and evaluated the association of patellofemoral and tibiofemoral OA features to unilateral AKP. In our second approach, MRIs from 1 knee per person were scored, and we evaluated the association of OA features to AKP in participants with AKP and participants with no frequent knee pain. RESULTS: Using the first approach (n = 71, 66% women, mean ± SD age 69 ± 8 years), lateral patellofemoral osteophytes (odds ratio [OR] 5.0 [95% confidence interval (95% CI) 1.7-14.6]), whole-knee joint effusion-synovitis (OR 4.7 [95% CI 1.3-16.2]), and infrapatellar synovitis (OR 2.8 [95% CI 1.0-7.8]) were associated with AKP. Using the second approach (n = 882, 59% women, mean ± SD age 69 ± 7 years), lateral and medial patellofemoral cartilage damage (prevalence ratio [PR] 2.3 [95% CI 1.3-4.0] and PR 1.9 [95% CI 1.1-3.3], respectively) and lateral patellofemoral BMLs (PR 2.6 [95% CI 1.5-4.7]) were associated with AKP. CONCLUSION: Patellofemoral but not tibiofemoral joint OA features and inflammation were associated with AKP.

Postoperative cognitive dysfunction after endovascular treatments for unruptured intracranial aneurysms: A pilot study.

OBJECTIVE: Post operative cognitive dysfunction (POCD) has been widely observed after major surgery, particularly in elderly patients with general anesthesia (GA). However, a specific unanswered question is whether different approaches to anesthetic managements are associated with different cognitive outcomes after endovascular treatments for unruptured intracranial aneurysms (UIAs). The purpose of this study is to assess the correlation of POCD with GA versus monitored anesthesia care (MAC). METHODS: We performed a pragmatic, prospective study to assess the association between different anesthetic approaches and POCD. We compared the pre- and post-procedural Montreal Cognitive Assessment (MoCA) scores in patients with normal cognition who underwent treatments of UIAs with various endovascular methods, using either GA or MAC. RESULTS: A total of 23 patients with UIAs were enrolled in the study. Seven (30.4%) and sixteen (69.6%) UIAs were treated without perioperative complications under GA or MAC, respectively. There was a significant decline in the post-procedural MoCA score under GA (mean difference = 1.14; 95% confidence interval = [0.42-1.87], P < 0.01). By contrast, there was no significant difference of MoCA score between pre- and post-procedure under MAC (mean difference = 0.19; 95% confidence interval = [-0.29-0.67], P = 0.59). CONCLUSIONS: Treating UIAs using MAC was associated with a decrease in POCD as compared to GA in patients undergoing endovascular treatments for UIAs with normal cognition. Larger randomized studies are needed to confirm these findings.

Rescue therapy for vasospasm following aneurysmal subarachnoid hemorrhage: a propensity score-matched analysis with machine learning.

OBJECTIVE: Rescue therapies have been recommended for patients with angiographic vasospasm (aVSP) and delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). However, there is little evidence from randomized clinical trials that these therapies are safe and effective. The primary aim of this study was to apply game theory-based methods in explainable machine learning (ML) and propensity score matching to determine if rescue therapy was associated with better 3-month outcomes following post-SAH aVSP and DCI. The authors also sought to use these explainable ML methods to identify patient populations that were more likely to receive rescue therapy and factors associated with better outcomes after rescue therapy. METHODS: Data for patients with aVSP or DCI after SAH were obtained from 8 clinical trials and 1 observational study in the Subarachnoid Hemorrhage International Trialists repository. Gradient boosting ML models were constructed for each patient to predict the probability of receiving rescue therapy and the 3-month Glasgow Outcome Scale (GOS) score. Favorable outcome was defined as a 3-month GOS score of 4 or 5. Shapley Additive Explanation (SHAP) values were calculated for each patient-derived model to quantify feature importance and interaction effects. Variables with high SHAP importance in predicting rescue therapy administration were used in a propensity score-matched analysis of rescue therapy and 3-month GOS scores. RESULTS: The authors identified 1532 patients with aVSP or DCI. Predictive, explainable ML models revealed that aneurysm characteristics and neurological complications, but not admission neurological scores, carried the highest relative importance rankings in predicting whether rescue therapy was administered. Younger age and absence of cerebral ischemia/infarction were invariably linked to better rescue outcomes, whereas the other important predictors of outcome varied by rescue type (interventional or noninterventional). In a propensity score-matched analysis guided by SHAP-based variable selection, rescue therapy was associated with higher odds of 3-month GOS scores of 4-5 (OR 1.63, 95% CI 1.22-2.17). CONCLUSIONS: Rescue therapy may increase the odds of good outcome in patients with aVSP or DCI after SAH. Given the strong association between cerebral ischemia/infarction and poor outcome, trials focusing on preventative or therapeutic interventions in these patients may be most able to demonstrate improvements in clinical outcomes. Insights developed from these models may be helpful for improving patient selection and trial design.

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.

Associations Between Sexual Assault and Reproductive and Family Planning Behaviors and Outcomes in Female Veterans.

OBJECTIVE: To examine the relationship between lifetime sexual assault (defined as someone having experienced sexual assault in their lifetime) and reproductive health care seeking, contraception usage, and family planning outcomes in female veterans. METHODS: We conducted a secondary analysis of data collected between 2005 and 2008 from computer-assisted telephone interviews with 1,004 female veterans aged 20-52 years who were enrolled at two Midwestern Department of Veterans Affairs (VA) health care systems. Participants were asked about reproductive, mental, and general health histories, and about lifetime sexual assault. We assessed associations between reproductive histories and contraceptive use among participants who reported lifetime sexual assault, compared with those who had not experienced lifetime sexual assault, by using bivariate and multivariable logistic regression analyses. Lastly, we examined reasons why these participants had not sought Pap test screening. RESULTS: More than half (62%) of participants reported experiencing lifetime sexual assault. Because there was an association between older age and history of lifetime sexual assault (P<.001), we stratified the analysis by age. Women with a history of lifetime sexual assault were more likely to have had unprotected intercourse for a year or more (adjusted odds ratio [aOR] 2.31, 95% CI 1.35-3.96) and a teen pregnancy (aOR 2.10, 95% CI 1.07-4.12) than women who did not report lifetime sexual assault. When stratified by age, women aged 40-52 years with a history of lifetime sexual assault were more likely to report more than a year of unprotected sex, teen pregnancy, and not seeking prenatal care with their first pregnancy, than women aged 40-52 who did not report lifetime sexual assault. Women who experienced lifetime sexual assault were more likely to report not seeking Pap tests in the past owing to fear and anxiety when compared with women who had not experienced lifetime sexual assault. CONCLUSION: Female veterans who reported lifetime sexual assault had differences in family planning behaviors compared with women who did not report lifetime sexual assault. These findings have implications for clinicians and VA policymakers when determining family planning and reproductive care delivery needs for female veterans of reproductive age.

Effects of fluoride intake on cortical and trabecular bone microstructure at early adulthood using multi-row detector computed tomography (MDCT).

PURPOSE: The aim of this study was to examine the effects of period-specific and cumulative fluoride (F) intake on bone at the levels of cortical and trabecular bone microstructural outcomes at early adulthood using emerging multi-row detector computed tomography (MDCT)-based novel techniques. METHODS: Ultra-high resolution MDCT distal tibia scans were collected at age 19 visits under the Iowa Bone Development Study (IBDS), and cortical and trabecular bone microstructural outcomes were computed at the distal tibia using previously validated methods. CT scans of a tissue characterization phantom were used to calibrate CT numbers (Hounsfield units) into bone mineral density (mg/cc). Period-specific and cumulative F intakes from birth up to the age of 19 years were assessed for IBDS participants through questionnaire, and their relationships with MDCT-derived bone microstructural outcomes were examined using bivariable and multivariable analyses, adjusting for height, weight, maturity offset (years since age of peak height velocity (PHV)), physical activity (questionnaire for adolescents (PAQ-A)), healthy eating index version 2010 (HEI-2010) scores, and calcium and protein intakes. RESULTS: MDCT distal tibia scans were acquired for 324 participants from among the total of 329 participants at age 19 visits. No motion artifacts were observed in any MDCT scans, and all images were successfully processed to measure cortical and trabecular bone microstructural outcomes. At early adulthood, males were observed to have stronger trabecular bone microstructural features, as well as thicker cortical bone (p < 0.01), as compared to age-similar females; however, females were found to have less cortical bone porosity as compared to males. Among participants with available F intake estimates (75 to 91% of the 324 with MDCT scans, depending on the period-specific F intake measure), no statistically significant associations were detected between any period-specific or cumulative F intake and bone microstructural outcomes of the tibia at the p < 0.01 level. Only for females, statistically suggestive associations (p < 0.05) were found between recent F intake (from 14 to 19 years) and trabecular mean plate width and trabecular thickness at the tibia. Those associations became somewhat weaker, but still statistically suggestive, for trabecular thickness in fully adjusted analysis with height, weight, PHV, calcium and protein intake, and HEI-2010 and PAQ-A scores as covariates. CONCLUSION: The findings show that the effects of lifelong or period-specific F intake from combined sources for adolescents typical to the United States Midwest region are not strongly associated with bone microstructural outcomes at age 19 years. These findings are generally consistent with previously reported results of IBDS analyses, which further confirms that effects of lifelong or period-specific F intake on skeletons in early adulthood are absent or weak, even at the levels of cortical and trabecular bone microstructural details.

Dural augmentation approaches and complication rates after posterior fossa decompression for Chiari I malformation and syringomyelia: a Park-Reeves Syringomyelia Research Consortium study.

OBJECTIVE: Posterior fossa decompression with duraplasty (PFDD) is commonly performed for Chiari I malformation (CM-I) with syringomyelia (SM). However, complication rates associated with various dural graft types are not well established. The objective of this study was to elucidate complication rates within 6 months of surgery among autograft and commonly used nonautologous grafts for pediatric patients who underwent PFDD for CM-I/SM. METHODS: The Park-Reeves Syringomyelia Research Consortium database was queried for pediatric patients who had undergone PFDD for CM-I with SM. All patients had tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and ≥ 6 months of postoperative follow-up after PFDD. Complications (e.g., pseudomeningocele, CSF leak, meningitis, and hydrocephalus) and postoperative changes in syrinx size, headaches, and neck pain were compared for autograft versus nonautologous graft. RESULTS: A total of 781 PFDD cases were analyzed (359 autograft, 422 nonautologous graft). Nonautologous grafts included bovine pericardium (n = 63), bovine collagen (n = 225), synthetic (n = 99), and human cadaveric allograft (n = 35). Autograft (103/359, 28.7%) had a similar overall complication rate compared to nonautologous graft (143/422, 33.9%) (p = 0.12). However, nonautologous graft was associated with significantly higher rates of pseudomeningocele (p = 0.04) and meningitis (p < 0.001). The higher rate of meningitis was influenced particularly by the higher rate of chemical meningitis (p = 0.002) versus infectious meningitis (p = 0.132). Among 4 types of nonautologous grafts, there were differences in complication rates (p = 0.02), including chemical meningitis (p = 0.01) and postoperative nausea/vomiting (p = 0.03). Allograft demonstrated the lowest complication rates overall (14.3%) and yielded significantly fewer complications compared to bovine collagen (p = 0.02) and synthetic (p = 0.003) grafts. Synthetic graft yielded higher complication rates than autograft (p = 0.01). Autograft and nonautologous graft resulted in equal improvements in syrinx size (p < 0.0001). No differences were found for postoperative changes in headaches or neck pain. CONCLUSIONS: In the largest multicenter cohort to date, complication rates for dural autograft and nonautologous graft are similar after PFDD for CM-I/SM, although nonautologous graft results in higher rates of pseudomeningocele and meningitis. Rates of meningitis differ among nonautologous graft types. Autograft and nonautologous graft are equivalent for reducing syrinx size, headaches, and neck pain.

Servicemen's Perceptions of Male Sexual Assault and Barriers to Reporting During Active Component and Reserve/National Guard Military Service.

Despite growing recognition of the high rates of sexual violence experienced by men serving in the U.S. military, male victimization, specifically sexual assault in military (SAIM), is an understudied topic. We qualitatively describe servicemen's awareness and perceptions of male SAIM, and their understanding of common barriers to servicemen reporting sexual assault. Participants included Midwestern Active Component and Reserve and National Guard servicemen, actively serving or Veteran, who had returned from Iraq or Afghanistan deployments during Operation Enduring/Iraqi Freedom eras. Eleven focus groups were held with 34 servicemen (20 Reserve/National Guard and 14 Active Component). Qualitative analyses used inductive and deductive techniques. Servicemen reported a lack of awareness of male SAIM, a tendency to blame or marginalize male victims, and substantial barriers to reporting sexual assault. Reserve/National Guard participants emphasized barriers such as a perception of greater stigma due to their unique status as citizen-soldiers, an ethos of unit conformity and leadership modeling, and a lack of confidence in leadership and the SAIM reporting process. In contrast, Active Component servicemen emphasized the deployment location and sex of victim and perpetrator as key reporting barriers. Findings make an important contribution to the scant literature on risk and protective factors for male SAIM and servicemen's perceptions of sexual violence and assault reporting barriers by their service type and location. This work has implications for routine screening for sexual violence experiences of male service members and Veterans. Providers' knowledge of gender stereotypes regarding sexual assault, assault risks and experiences of deployed servicemen, and potential barriers to SAIM disclosure is vital for patient-centered care delivery. Additional research to address factors that influence post-SAIM care engagement of males is indicated.

Factors Associated with U.S. Military Women Keeping Guns or Weapons Nearby for Personal Security Following Deployment.

Background: The relationship between postdeployment health characteristics and U.S. military women and women Veteran's gun/weapons use for personal safety outside of military is not well understood. The purpose of this exploratory study was to determine if Operation Enduring and Iraqi Freedom era military women and women Veterans keep guns/weapons nearby for personal security outside of military duties postdeployment and factors associated with this. Methods: A Midwestern community sample of US Army and Air Force currently serving Military women and women Veterans (N = 978) who had deployed to Iraq/Afghanistan (I/A) or outside of the United States completed telephone interviews (March 2010 to December 2011) querying sociodemographic and military characteristics, combat and gender-based trauma, and guns/weapons use postdeployment. Data were analyzed in June 2019 with chi-square, Fisher's Exact test, and odds ratios. A classification tree analysis identified subgroups with the greatest proportion of keeping guns/weapons nearby for security. Results: One-fifth of participants reported having guns/weapons nearby to feel secure. Women more likely to report this were younger, patrolled their homes for security (age adjusted odds ratio [aOR] 7.0); experienced combat (aOR 3.0-4.9) or gender-based traumas (aOR 1.9-2.0); self-reported mental health conditions (aOR 1.5-4.3), including post-traumatic stress disorder (PTSD; aOR 4.3); or relied on friends/family for housing (aOR 4.8). Most had seen a provider in the preceding year. The classification tree found women patrolling their homes, PTSD positive, and injured/wounded in I/A had the largest proportion of women keeping guns/weapons nearby for security. Conclusions: Keeping gun/weapons nearby for personal self-defense is a potential marker for complex postdeployment readjustment conditions and an overlooked public health concern. Provider recognition and assessment of women's postdeployment fears and safety-related activities are essential to address military women and women Veterans and their families' safety in this high-risk population.

Lifetime History of Sexual Assault and Emergency Department Service Use among Women Veterans.

BACKGROUND: Although sexual assault survivors are at increased risk for adverse physical and mental health outcomes and tend to use more health care services, little is known about women veterans' lifetime history of experiencing sexual assault (lifetime sexual assault [LSA]) and emergency department (ED) use. We sought to examine associations between experiencing LSA, mental health diagnoses, and ED use among women veterans. METHODS: Computer-assisted telephone interviews were conducted with 980 women veterans enrolled at two Veterans Affairs (VA) Medical Centers to assess history of experiencing LSA, health care use, sociodemographic characteristics, and military history. Administrative data provided VA use, mental health, and medical diagnoses. Logistic regression analyses examined associations between experiencing LSA and mental health diagnoses and past 5-year ED use. Classification tree analysis characterized ED use in participant subgroups. RESULTS: Sixty-four percent of participants visited a VA or non-VA ED during the previous 5 years. Women veterans with histories of mental health diagnoses and who experienced sexual assault had an odds of ED use almost two times greater than those with no history of experiencing sexual assault and no mental health diagnoses. The odds were similar for experiencing attempted (adjusted odds ratio, 1.85) and completed (adjusted odds ratio, 1.95) sexual assault. Classification tree analysis identified reliance on VA care and the composite variable representing experiencing LSA and mental health diagnoses as factors that best discriminated ED users from nonusers. CONCLUSIONS: Experiencing LSA is associated with greater ED use in women veterans enrolled in the VA. Whether finding this reflects greater emergent health care needs, suboptimal access and treatment for conditions that could be managed in other settings, lack of health care coordination, or some combination of these factors is unclear.

Quantitative Susceptibility Mapping and Vessel Wall Imaging as Screening Tools to Detect Microbleed in Sentinel Headache.

BACKGROUND: MR-quantitative susceptibility mapping (QSM) can identify microbleeds (MBs) in intracranial aneurysm (IA) wall associated with sentinel headache (SH) preceding subarachnoid hemorrhage. However, its use is limited, due to associated skull base bonny and air artifact. MR-vessel wall imaging (VWI) is not limited by such artifact and therefore could be an alternative to QSM. The purpose of this study was to investigate the correlation between QSM and VWI in detecting MBs and to help develop a diagnostic strategy for SH. METHODS: We performed a prospective study of subjects with one or more unruptured IAs in our hospital. All subjects underwent evaluation using 3T-MRI for MR angiography (MRA), QSM, and pre- and post-contrast VWI of the IAs. Presence/absence of MBs detected by QSM was correlated with aneurysm wall enhancement (AWE) on VWI. RESULTS: A total of 40 subjects harboring 51 unruptured IAs were enrolled in the study. MBs evident on the QSM sequence was detected in 12 (23.5%) IAs of 11 subjects. All these subjects had a history of severe headache suggestive of SH. AWE was detected in 22 (43.1%) IAs. Using positive QSM as a surrogate for MBs, the sensitivity, specificity, positive predictive value, and negative predictive value of AWE on VWI for detecting MBs were 91.7%, 71.8%, 50%, and 96.6%, respectively. CONCLUSIONS: Positive QSM findings strongly suggested the presence of MBs with SH, whereas, the lack of AWE on VWI can rule it out with a probability of 96.6%. If proven in a larger cohort, combining QSM and VWI could be an adjunctive tool to help diagnose SH, especially in cases with negative or non-diagnostic CT and lumbar puncture.

Deep Learning Based High-Resolution Reconstruction of Trabecular Bone Microstructures from Low-Resolution CT Scans using GAN-CIRCLE.

Osteoporosis is a common age-related disease characterized by reduced bone density and increased fracture-risk. Microstructural quality of trabecular bone (Tb), commonly found at axial skeletal sites and at the end of long bones, is an important determinant of bone-strength and fracture-risk. High-resolution emerging CT scanners enable in vivo measurement of Tb microstructures at peripheral sites. However, resolution-dependence of microstructural measures and wide resolution-discrepancies among various CT scanners together with rapid upgrades in technology warrant data harmonization in CT-based cross-sectional and longitudinal bone studies. This paper presents a deep learning-based method for high-resolution reconstruction of Tb microstructures from low-resolution CT scans using GAN-CIRCLE. A network was developed and evaluated using post-registered ankle CT scans of nineteen volunteers on both low- and high-resolution CT scanners. 9,000 matching pairs of low- and high-resolution patches of size 64×64 were randomly harvested from ten volunteers for training and validation. Another 5,000 matching pairs of patches from nine other volunteers were used for evaluation. Quantitative comparison shows that predicted high-resolution scans have significantly improved structural similarity index (p < 0.01) with true high-resolution scans as compared to the same metric for low-resolution data. Different Tb microstructural measures such as thickness, spacing, and network area density are also computed from low- and predicted high-resolution images, and compared with the values derived from true high-resolution scans. Thickness and network area measures from predicted images showed higher agreement with true high-resolution CT (CCC = [0.95, 0.91]) derived values than the same measures from low-resolution images (CCC = [0.72, 0.88]).

CT-Based Characterization of Transverse and Longitudinal Trabeculae and Its Applications.

Osteoporosis is a common age-related disease characterized by reduced bone mineral density (BMD), micro-structural deterioration, and enhanced fracture-risk. Although, BMD is clinically used to define osteoporosis, there are compelling evidences that bone micro-structural properties are strong determinants of bone strength and fracture-risk. Reliable measures of effective trabecular bone (Tb) micro-structural features are of paramount clinical significance. Tb consists of transverse and longitudinal micro-structures, and there is a hypothesis that transverse trabeculae improve bone strength by arresting buckling of longitudinal trabeculae. In this paper, we present an emerging clinical CT-based new method for characterizing transverse and longitudinal trabeculae, validate the method, and examine its application in human studies. Specifically, we examine repeat CT scan reproducibility, and evaluate the relationships of these measures with gender and body size using human CT data from the Iowa Bone Development Study (IBDS) (n = 99; 49 female). Based on a cadaveric ankle study (n = 12), both transverse and longitudinal Tb measures are found reproducible (ICC > 0.94). It was observed in the IBDS human data that males have significantly higher trabecular bone measures than females for both inner (p < 0.05) and outer (p < 0.01) regions of interest (ROIs). For weight, Spearman correlations ranged 0.43-0.48 for inner ROI measures and 0.50-0.52 for outer ROI measures for females versus 0.30-0.34 and 0.23-0.25 for males. Correlation with height was lower (0.36-0.39), but still mostly significant for females. No association of trabecular measures with height was found for males.

Psychological and Pain Sensitization Characteristics Are Associated With Patellofemoral Osteoarthritis Symptoms: The Multicenter Osteoarthritis Study.

OBJECTIVE: Determine the relation of symptomatic and structural features of patellofemoral osteoarthritis (PFOA) to psychological characteristics and measures of pain sensitization, in older adults with or at risk of knee osteoarthritis (OA). METHODS: This study included 1112 participants from the Multicenter Osteoarthritis Study (713 females, mean age 66.8 ± SD 7.6 yrs, body mass index 29.5 ± 4.8 kg/m2). Participants were grouped based on the presence of PFOA symptoms (anterior knee pain and pain on stairs) and magnetic resonance imaging (MRI) PFOA (full-thickness cartilage lesion with bone marrow lesion): (1) patellofemoral (PF) symptoms with MRI PFOA; (2) PF symptoms without MRI PFOA; (3) MRI PFOA without PF symptoms; and (4) no PF symptoms or MRI PFOA (no PFOA). Relation of PFOA classification to depressive symptoms, catastrophizing, temporal summation (TS) and pressure pain thresholds (PPT) was evaluated using logistic (categorical variables) and linear regression (continuous variables). RESULTS: Compared with no PFOA, those with PF symptoms with or without MRI PFOA had significantly greater odds of depressive symptoms, catastrophizing, and patellar TS (OR range 1.5-2.01), and those with PF symptoms without MRI PFOA had significantly greater odds of wrist TS (OR 1.66). Males with PF symptoms without MRI PFOA had significantly lower pressure PPT at the patella compared with no PFOA and those with MRI PFOA only (no symptoms). There were no significant differences at the wrist for males, or the patella or wrist for females. CONCLUSION: Persons with PFOA symptoms, regardless of MRI PFOA status, are more likely to demonstrate depressive symptoms, catastrophizing, and TS. Males with PFOA symptoms without MRI PFOA demonstrate local hyperalgesia.