Dexmedetomidine HCL (BXCL501) as a potential treatment for alcohol use disorder and comorbid PTSD: A phase 1b, placebo-controlled crossover laboratory study.

BACKGROUND AND OBJECTIVES: Noradrenergic dysregulation is important in the pathophysiology of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD); pharmacotherapies targeting adrenergic function have potential as treatment for comorbidity. Dexmedetomidine (sublingual film formulation-BXCL501; IGALMI) is a highly potent, selective ⍺2-adrenergic receptor agonist and may be superior to other pharmacotherapeutic approaches. A within subjects, phase 1b safety laboratory study was conducted to evaluate adverse effects of BXCL501 when combined with alcohol; BXCL501's potential efficacy was also explored. METHODS: Heavy drinker participants with a diagnosis of or who were at risk for PTSD participated in three separate test days which included pretreatment with BXCL501 (40 µg, 80 µg or placebo) administered in a randomized, double-blind fashion, followed by three testing conditions: alcohol cue reactivity, trauma-induced reactivity, and IV ethanol administration. Safety outcomes included blood pressure (BP) and sedation. Exploratory outcomes included alcohol craving, trauma-induced anxiety and craving and subjective effects of alcohol. RESULTS: Ten of twelve randomized participants competed the entire study. BXCL501 (80 µg) was associated with expected mild changes in BP and sedation; administration with alcohol did not affect those parameters. There were no clinically significant adverse effects. BXCL501 attenuated trauma-induced anxiety and attenuated subjective effects of alcohol. DISCUSSIONS AND CONCLUSIONS: BXCL501 is safe for use in humans who may drink alcohol while undergoing treatment. BXCL501 may be explored as a potential treatment for PTSD and AUD. SCIENTIFIC SIGNIFICANCE: This is the first study to provide scientific support for BXCL501's potential to treat PTSD and comorbid AUD.

Relationships between retinopathy of prematurity without ophthalmologic intervention and neurodevelopment and vision at 2 years.

BACKGROUND: Severe retinopathy of prematurity (ROP) is associated with adverse outcomes. Relationships between milder ROP and outcomes have not been defined. We hypothesized that children with ROP stage ≤3 who did not receive ophthalmologic intervention would have worse motor, cognitive, and language skills and more vision abnormalities than children without ROP. METHODS: This was a secondary analysis of a randomized trial evaluating the effects of myo-inositol on ROP in the NICHD Neonatal Research Network. Primary outcomes were Bayley Scales of Infant Development composite scores; secondary outcomes included behavioral difficulties and ophthalmologic measures. Outcomes were compared using adjusted linear or modified Poisson models. RESULTS: Of 506 children, 173 (34%) had no ROP, 262 (52%) had ROP stage ≤3 without intervention, and 71 (14%) had ROP with intervention. There was no difference in motor, cognitive, or language scores between children with ROP stage ≤3 without intervention and children without ROP. Children with ROP stage ≤3 without intervention had a higher rate of strabismus compared to children without ROP (p = 0.040). CONCLUSION: Children with ROP stage ≤3 without intervention did not have adverse neurodevelopmental outcomes at 2 years' corrected age compared to children without ROP but did have an increased incidence of strabismus. IMPACT: This study addresses a gap in the literature regarding the relationship between milder forms of retinopathy of prematurity (ROP) that regress without intervention and neurodevelopment and vision outcomes. Children with a history of ROP stage ≤3 without intervention have similar neurodevelopmental outcomes at 2 years' corrected age as children born extremely preterm without a history of ROP and better outcomes than children with a history of ROP with ophthalmologic intervention. Counseling about likely neurodevelopment and vision outcomes for children born extremely preterm with a history of ROP may be tailored based on the severity of ROP. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: Inositol to Reduce Retinopathy of Prematurity Trial: NCT01954082.

Health Services Utilization, Health Care Costs, and Diagnoses by Mild Traumatic Brain Injury Exposure: A Chronic Effects of Neurotrauma Consortium Study.

OBJECTIVE: To compare Veterans Health Administration (VHA) diagnoses, health services utilization, and costs by mild traumatic brain injury (mTBI) group (blast-related [BR] mTBI vs non-blast-related [NBR] mTBI vs no mTBI) among Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF)/Operation New Dawn (OND) veterans in the Chronic Effects of Neurotrauma Consortium multicenter observational study. DESIGN: Prospective cohort study. SETTING: Four Veterans Affairs Medical Centers. PARTICIPANTS: OEF/OIF/OND veterans (N=472) who used Veterans Affairs Medical Centers services between 2002-2017. INTERVENTIONS: Not applicable. Lifetime mTBI history was assessed via semistructured interviews. MAIN OUTCOME MEASURES: VHA diagnoses, health services utilization, and costs. RESULTS: Relative to NBR mTBI and no mTBI, veterans with BR mTBI were more likely to be male, have greater combat, and have controlled and uncontrolled detonations exposures (median BR, 15.0 vs NBR, 3.0 vs no mTBI, 3.0). They also had higher prevalence of headache, posttraumatic stress disorder, and anxiety diagnoses. Veterans with BR had the highest site-adjusted mean annual VHA utilization (26.31 visits; 95% confidence interval [CI], 26.01-26.61) relative to NBR (20.43 visits; 95% CI, 20.15-20.71) and no mTBI (16.62 visits; 95% CI, 16.21-17.04) and highest site adjusted mean annual VHA outpatient costs ($6480; 95% CI, $5842-$7187) relative to NBR ($4901; 95% CI, $4392-$5468) and no mTBI ($4069; 95% CI, $3404-$4864). CONCLUSIONS: Veterans with BR mTBI had higher exposure to combat and detonation. BR was associated with greater prevalence of select diagnoses and higher health services utilization and costs relative to NBR and no mTBI. The role of health care needs from mTBI polytrauma, other deployment-related exposures, and VHA access warrants future research.

Longitudinal evaluation of ventricular volume changes associated with mild traumatic brain injury in military service members.

PRIMARY OBJECTIVE: To investigate differences in longitudinal trajectories of ventricle-brain ratio (VBR), a general measure of brain atrophy, between Veterans with and without history of mild traumatic brain injury (mTBI). RESEARCH DESIGN: Structural magnetic resonance imaging (MRI) was used to calculate VBR in 70 Veterans with a history of mTBI and 34 Veterans without such history at two time points approximately 3 and 8 years after a combat deployment. MAIN OUTCOMES AND RESULTS: Both groups demonstrated a quadratic relationship between VBR and age that is consistent with normal developmental trajectories. Veterans with history of mTBI had larger total brain volume, but no interaction between mTBI and age was observed for brain volume, ventricular volume, or VBR. CONCLUSIONS: In our longitudinal sample of deployed Veterans, mTBI was not associated with gross brain atrophy as reflected by abnormally high VBR or abnormal increases in VBR over time.

Healthcare professional involvement and RTP compliance in high school athletes with concussion.

OBJECTIVES: To describe concussion rates in high school athletes and involvement of healthcare professionals in concussion diagnosis, management and compliance with return to play (RTP) guidelines. METHODS: Data were analysed from injury reports in the National High School Sports-Related Injury Surveillance System between 2009/2010 and 2012/2013 to identify student athletes with concussion and determine compliance with RTP guidelines. Compliance with RTP guidelines was examined using logistic regression, adjusting for sport and injury-related variables. RESULTS: There were 5611 concussions recorded during 15 712 475 athlete exposures (AEs), a rate of 3.6 concussions per 10 000 AEs. Rates were higher during competition and among girls compared to boys in gender equitable sports. Healthcare professionals were less likely to be present at the time of concussion for girls' sports, lower competition levels and practices. Compliance with RTP guidelines was higher for athletes with recurrent concussions, those sustained in collision sports, for athletes reporting more symptoms and when a physician made the RTP decision. CONCLUSIONS: Presence of healthcare professionals and compliance with RTP guidelines varied by sport, gender, level of play and exposure type. High school athletes with concussion are best served by assessment teams with athletic trainers and physicians working together to manage concussions and contribute to RTP decisions.

Chronic Effects of Neurotrauma Consortium (CENC) multicentre study interim analysis: Differences between participants with positive versus negative mild TBI histories.

OBJECTIVES: Compare characteristics and outcomes of combat-exposed military personnel with positive versus negative mild traumatic brain injury (mTBI) histories. SETTING: Recruitment was from registration lists and ambulatory clinics at four veterans administration hospitals. PARTICIPANTS: Consented veterans and service members completing initial evaluation by September 2016 (n = 492). DESIGN: Observational with cross-sectional analyses. MAIN MEASURES: Multimodal assessments including structured interviews, record review, questionnaires, neuroendocrine labs and neurocognitive and sensorimotor performance. RESULTS: In unadjusted comparisons to those absent lifetime mTBI, the mTBI positive group (84%) had greater combat exposure, more potential concussive events, less social support and more comorbidities, including asthma, sleeping problems and post-traumatic stress disorder. They also fared worse on all sensory and pain symptom scores and self-reported functional and global outcomes. They had poorer scores on Wechsler Adult Intelligence Scale-IV coding (processing speed), TMT-B (visual-motor integration and executive function) and two posturography subtests, but were otherwise equal to TBI negative participants on neurocognitive and sensorimotor testing and neuroendocrine levels. CONCLUSIONS: Although differences in characteristics exist which were not adjusted for, participants with historical mTBI have greater symptomatology and life functioning difficulties compared with non-TBI. Performance measures were less dissimilar between groups. These findings will guide further research within this accruing cohort.

Exploring the factor structure of a battery of neuropsychological assessments among the CENC cohort.

OBJECTIVE: The goal of the Chronic Effects of Neurotrauma Consortium (CENC) study is to explore the effects of concussions among Service Members and Veterans. A factor model was fit to selected neuropsychological measures to identify potentially useful relationships between assessments collected on CENC-enrolled participants. METHOD: 492 post-9/11 participants with combat exposure were enrolled across four VA study sites. Participants completed assessments including concussion history, neurocognitive functioning, and self-report questionnaires. Exploratory factor analyses (EFA) using four different methods with varimax and promax rotations were used to analyse the cognitive variables. Final model selection was based on factor loadings towards simple structure. RESULTS: The scree plot suggested the number of factors to be extracted was between 4 and 5. EFA produced a 5-factor MINRES model with promax rotation that resulted in a factor loading with variables loading on only one factor with a predefined threshold (0.40). Variables loaded on five cognition domains: list learning, working memory/executive skills, cognitive control, fluency, and memory. CONCLUSION: These results provide reasonable evidence that data collected from the CENC neuropsychological battery can be reduced to five clinically useful factors. This will enable us to use the factors for further study of the impact of concussion on neurodegeneration.

Understanding the impact of mild traumatic brain injury on veteran service-connected disability: results from Chronic Effects of Neurotrauma Consortium.

OBJECTIVES: Disability evaluation is complex. The association between mild traumatic brain injury (mTBI) history and VA service-connected disability (SCD) ratings can have implications for disability processes in the civilian population. We examined the association of VA SCD ratings with lifetime mTBI exposure in three models: any mTBI, total mTBI number, and blast-related mTBI. METHODS: Participants were 492 Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans from four US VA Medical Centers enrolled in the Chronic Effects of Neurotrauma Consortium study between January 2015 and August 2016. Analyses entailed standard covariate-adjusted linear regression models, accounting for demographic, military, and health-related confounders and covariates. RESULTS: Unadjusted and adjusted results indicated lifetime mTBI was significantly associated with increased SCD, with the largest effect observed for blast-related mTBI. Every unit increase in mTBI was associated with an increase in 3.6 points of percent SCD. However, hazardous alcohol use was associated with lower SCD. CONCLUSIONS: mTBI, especially blast related, is associated with higher VA SCD ratings, with each additional mTBI increasing percent SCD. The association of hazardous alcohol use with SCD should be investigated as it may impact veteran health services access and health outcomes. These findings have implications for civilian disability processes.

Differential posttraumatic stress disorder symptom cluster response to stellate ganglion block: secondary analysis of a randomized controlled trial.

Empirically supported treatments for posttraumatic stress disorder (PTSD) exist, but research suggests these therapies are less effective, acceptable, and feasible to deliver to active duty service members (SMs) compared to civilians. Stellate ganglion block (SGB) procedure, in which a local anesthetic is injected around the cervical sympathetic chain or stellate ganglion to temporarily inhibit sympathetic nervous activity, is gaining popularity as an alternative PTSD treatment in military settings. However, it is unknown whether certain PTSD symptoms are more responsive to SGB than others. The current study involved a secondary analysis of data collected from a previous randomized controlled trial of SGB compared to sham (normal saline) injection (N = 113 SMs). PTSD symptoms were assessed via clinical interview and self-report at baseline and 8 weeks post-SGB or sham. Logistic regression analyses showed that the marked alterations in arousal and reactivity PTSD symptom cluster demonstrated the greatest symptom severity reductions after SGB, relative to sham. The reexperiencing cluster also showed pronounced response to SGB in clinician-rated but not self-reported outcomes. Post-hoc item-level analyses suggested that arousal and reactivity cluster findings were driven by reductions in hypervigilance, concentration difficulties, and sleep disturbance, whereas clinician-rated reexperiencing cluster findings were driven by reductions in physiological reactions to trauma cues, emotional reactions to trauma cues, and intrusions. Our findings align with a burgeoning literature positioning SGB as a potential novel or adjunctive PTSD treatment. Results could guide future hypothesis-driven research on mediators of therapeutic change during SGB for PTSD symptoms in SMs.

Comorbid alcohol use disorder and posttraumatic stress disorder: A proof-of-concept randomized placebo-controlled trial of buprenorphine and naltrexone combination treatment.

BACKGROUND: Effective pharmacologic treatments for comorbid alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are lacking. Kappa (κ) opioid receptor antagonists may address this unmet need. Buprenorphine is a κ-opioid antagonist and a partial agonist of mu (µ) opioid receptors. Whereas naltrexone blocks all µ-mediated effects combining it with buprenorphine yields a pharmacologic net effect of opioid receptor antagonism. Because no κ-opioid receptor antagonist it available for clinical use, we tested this combination in a proof-of-concept study. METHODS: Consenting participants were enrolled in a Phase II, multisite, double-blind, randomized, placebo-controlled trial evaluating the effectiveness of sublingual (SL) buprenorphine combined with extended-release (XR) injectable naltrexone for the treatment of comorbid AUD and PTSD. Eligible participants (n = 75) were randomized (1:1:1) to receive either buprenorphine 2 mg/day plus naltrexone-XR (n = 35), buprenorphine 8 mg/day plus naltrexone-XR (n = 6) or SL plus injectable placebo (n = 34) for 12 weeks. The buprenorphine 8 mg/day plus naltrexone-XR arm was dropped early in the trial due to the negative impact of COVID-19 on enrollment. A binary primary outcome of response at week 8 was defined as a decrease from baseline of ≥10 points on the past week Clinician-Administered PTSD Scale (CAPS-5) and a reduction of ≥1 of past month alcohol risk level, as defined by the World Health Organization (WHO) and measured by the Timeline Follow-Back. RESULTS: Based on the results of a futility analysis, enrollment was stopped prior to reaching the initial goal of 90 participants. At the week eight primary timepoint, there were no statistically significant differences between buprenorphine plus naltrexone-XR and placebo group for the primary composite outcome (OR = 0.63; p-value = 0.52), or the subcomponents of the PTSD outcome (OR = 0.76; p-value = 0.69) and AUD outcome (OR = 0.17; p-value = 0.08). The placebo arm had a significantly higher proportion of participants with ≥1 WHO risk level reduction than the buprenorphine plus naltrexone-XR arm (OR = 0.18, p value = 0.02). CONCLUSIONS: This is the first study to evaluate the potential of κ-opioid receptor antagonism for the treatment of comorbid AUD and PTSD. The combination of buprenorphine and naltrexone-XR showed no significant improvement over placebo for the composite, PTSD, or alcohol measures.

FKBP5 inhibitors modulate alcohol drinking and trauma-related behaviors in a model of comorbid post-traumatic stress and alcohol use disorder.

Post-traumatic stress disorder (PTSD) leads to enhanced alcohol drinking and development of alcohol use disorder (AUD). Identifying shared neural mechanisms might help discover new therapies for PTSD/AUD. Here, we employed a rat model of comorbid PTSD/AUD to evaluate compounds that inhibit FK506-binding protein 51 (FKBP5), a co-chaperone modulator of glucocorticoid receptors implicated in stress-related disorders. Male and female rats received a familiar avoidance-based shock stress followed by voluntary alcohol drinking. We then assessed trauma-related behaviors through sleep bout cycles, hyperarousal, fear overgeneralization, and irritability. To evaluate the role of stress and alcohol history on the sensitivity to FKBP5 inhibitors, in two separate studies, we administered two FKBP5 inhibitors, benztropine (Study 1) or SAFit2 (Study 2). FKBP5 inhibitors were administered on the last alcohol drinking session and prior to each trauma-related behavioral assessment. We also measured plasma corticosterone to assess the actions of FKBP5 inhibitors after familiar shock stress and alcohol drinking. Benztropine reduced alcohol preference in stressed males and females, while aggressive bouts were reduced in benztropine-treated stressed females. During hyperarousal, benztropine reduced several startle response outcomes across stressed males and females. Corticosterone was reduced in benztropine-treated stressed males. The selective FKBP5 inhibitor, SAFit2, reduced alcohol drinking in stressed males but not females, with no differences in irritability. Importantly, SAFit2 decreased fear overgeneralization in stressed males and females. SAFit2 also reduced corticosterone across stressed males and females. Neither FKBP5 inhibitor changed sleep bout structure. These findings indicate that FKBP5 inhibitors modulate stress-related alcohol drinking and partially modulate trauma-related behaviors. This work supports the hypothesis that targeting FKBP5 may alleviate PTSD/AUD comorbidity.

A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers.

PT150, a novel competitive glucocorticoid receptor (GR) antagonist, has proven safe in animal models, healthy volunteers, and people with depression. Our study is the first to investigate PT150's safety with alcohol use. The primary objective of this study was to evaluate pharmacodynamic interactions between ethanol and PT150 in healthy subjects. This single-site, Phase I pilot trial consisted of community-recruited, healthy, alcohol-experienced participants aged 21-64 years. Of 32 participants screened, 11 were enrolled and randomized, one of which withdrew before intervention. PT150 (900 mg/day) was administered orally to all participants for five days. All participants received two beverage challenges on Day 1 (before PT150 administration) and Day 5 (after PT150 administration). On challenge days, they received both alcohol (16% ethanol) and placebo (1% ethanol) beverages in random order. Primary outcomes included breath alcohol level, blood pressure, heart rate, adverse events, and electrocardiogram changes. There were no statistically significant differences in vital signs or estimated blood alcohol concentrations between PT150 non-exposed and exposed groups during the ethanol challenge. There were no clinically significant abnormal electrocardiograms or serious adverse events. These data show that administration of PT150 with concurrent alcohol use is safe and well-tolerated. This study supports a future pharmacokinetic interaction study between PT150 and alcohol.Trial Registration ClinicalTrials.gov Identifier: NCT03548714.

Neurodevelopmental outcome of preterm infants enrolled in myo-inositol randomized controlled trial.

OBJECTIVE: This study evaluates the 24-month follow-up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial. STUDY DESIGN: Bayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score <85, moderate or severe cerebral palsy, blindness, or hearing loss that prevents communication despite amplification were assessed. RESULTS: Primary outcome was determined for 605/638 (95%). The mean gestational age was 25.8 ± 1.3 weeks and mean birthweight was 805 ± 192 g. Treatment group did not affect the risk for the composite outcome of death or survival with moderate/severe NDI (60% vs 56%, p = 0.40). CONCLUSIONS: Treatment group did not affect the risk of death or survival with moderate/severe NDI. Despite early termination, this study represents the largest RCT of extremely preterm infants treated with myo-inositol with neurodevelopmental outcome data.

Effect of Stellate Ganglion Block Treatment on Posttraumatic Stress Disorder Symptoms: A Randomized Clinical Trial.

Importance: This is the first multisite, randomized clinical trial of stellate ganglion block (SGB) outcomes on posttraumatic stress disorder (PTSD) symptoms. Objective: To determine whether paired SGB treatments at 0 and 2 weeks would result in improvement in mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total symptom severity scores from baseline to 8 weeks. Design, Setting, and Participants: This multisite, blinded, sham-procedure, randomized clinical trial used a 2:1 SGB:sham ratio and was conducted from May 2016 through March 2018 in 3 US Army Interdisciplinary Pain Management Centers. Only physicians performing the procedures and the procedure nurses were aware of the intervention (but not the participants or assessors); their interactions with the participants were scripted and limited to the 2 interventions. Active-duty service members on stable psychotropic medication dosages who had a PTSD Checklist-Civilian Version (PCL-C) score of 32 or more at screening were included. Key exclusion criteria included a prior SGB treatment, selected psychiatric disorders or substance use disorders, moderate or severe traumatic brain injury, or suicidal ideation in the prior 2 months. Interventions: Paired right-sided SGB or sham procedures at weeks 0 and 2. Main Outcomes and Measures: Improvement of 10 or more points on mean CAPS-5 total symptom severity scores from baseline to 8 weeks, adjusted for site and baseline total symptom severity scores (planned a priori). Results: Of 190 screened individuals, 113 (59.5%; 100 male and 13 female participants; mean [SD] age, 37.3 [6.7] years) were eligible and randomized (74 to SGB and 39 to sham treatment), and 108 (95.6% of 113) completed the study. Baseline characteristics were similar in the SGB and sham treatment groups, with mean (SD) CAPS-5 scores of 37.6 (11.2) and 39.8 (14.4), respectively (on a scale of 0-80); 91 (80.0%) met CAPS-5 PTSD criteria. In an intent-to-treat analysis, adjusted mean total symptom severity score change was -12.6 points (95% CI, -15.5 to -9.7 points) for the group receiving SGB treatments, compared with -6.1 points (95% CI, -9.8 to -2.3 points) for those receiving sham treatment (P = .01). Conclusions and Relevance: In this trial of active-duty service members with PTSD symptoms (at a clinical threshold and subthreshold), 2 SGB treatments 2 weeks apart were effective in reducing CAPS-5 total symptom severity scores over 8 weeks. The mild-moderate baseline level of PTSD symptom severity and short follow-up time limit the generalizability of these findings, but the study suggests that SGB merits further trials as a PTSD treatment adjunct. Trial Registration: ClinicalTrials.gov identifier: NCT03077919.

Inhalation cancer risk assessment of hexavalent chromium based on updated mortality for Painesville chromate production workers.

The exposure-response for hexavalent chromium (Cr(VI))-induced lung cancer among workers of the Painesville Ohio chromate production facility has been used internationally for quantitative risk assessment of environmental and occupational exposures to airborne Cr(VI). We updated the mortality of 714 Painesville workers (including 198 short-term workers) through December 2011, reconstructed exposures, and conducted exposure-response modeling using Poisson and Cox regressions to provide quantitative lung cancer risk estimates. The average length of follow-up was 34.4 years with 24,535 person-years at risk. Lung cancer was significantly increased for the cohort (standardized mortality ratio (SMR)=186; 95% confidence interval (CI) 145-228), for those hired before 1959, those with >30-year tenure, and those with cumulative exposure >1.41 mg/m(3)-years or highest monthly exposures >0.26 mg/m(3). Of the models assessed, the linear Cox model with unlagged cumulative exposure provided the best fit and was preferred. Smoking and age at hire were also significant predictors of lung cancer mortality. Adjusting for these variables, the occupational unit risk was 0.00166 (95% CI 0.000713-0.00349), and the environmental unit risk was 0.00832 (95% CI 0.00359-0.0174), which are 20% and 15% lower, respectively, than values developed in a previous study of this cohort.

Gynecologic oncologists involvement on ovarian cancer standard of care receipt and survival.

AIM: To examine the influence of gynecologic oncologists (GO) in the United States on surgical/chemotherapeutic standard of care (SOC), and how this translates into improved survival among women with ovarian cancer (OC). METHODS: Surveillance, Epidemiology, and End Result (SEER)-Medicare data were used to identify 11688 OC patients (1992-2006). Only Medicare recipients with an initial surgical procedure code (n = 6714) were included. Physician specialty was identified by linking SEER-Medicare to the American Medical Association Masterfile. SOC was defined by a panel of GOs. Multivariate logistic regression was used to determine predictors of receiving surgical/chemotherapeutic SOC and proportional hazards modeling to estimate the effect of SOC treatment and physician specialty on survival. RESULTS: About 34% received surgery from a GO and 25% received the overall SOC. One-third of women had a GO involved sometime during their care. Women receiving surgery from a GO vs non-GO had 2.35 times the odds of receiving the surgical SOC and 1.25 times the odds of receiving chemotherapeutic SOC (P < 0.01). Risk of mortality was greater among women not receiving surgical SOC compared to those who did [hazard ratio = 1.22 (95%CI: 1.12-1.33), P < 0.01], and also was higher among women seen by non-GOs vs GOs (for surgical treatment) after adjusting for covariates. Median survival time was 14 mo longer for women receiving combined SOC. CONCLUSION: A survival advantage associated with receiving surgical SOC and overall treatment by a GO is supported. Persistent survival differences, particularly among those not receiving the SOC, require further investigation.

Prevalence of psoriasis among adults in the U.S.: 2003-2006 and 2009-2010 National Health and Nutrition Examination Surveys.

BACKGROUND: A 2010 CDC-sponsored consultation of psoriasis, psoriatic arthritis, and public health experts developed a public health agenda for psoriasis and psoriatic arthritis indicating that additional population-based research is needed to better characterize psoriasis in the population. PURPOSE: To better characterize the burden of psoriasis in the U.S. using recent population-based, cross-sectional data in this 2012 analysis. METHODS: A subset of 10,676 adults aged 20-59 years from the 2003-2006 and 2009-2010 National Health and Nutrition Examination Surveys was used to examine psoriasis prevalence, severity, disparities, health-related quality of life, and selected comorbidities. RESULTS: The overall prevalence of psoriasis was 3.1% (95% CI=2.6, 3.6); extrapolating to older adults suggests that 6.7 million adults aged ≥20 years are affected. Psoriasis was significantly more prevalent among non-Hispanic whites than other race/ethnicity subgroups, as well as among those with arthritis. Approximately 82% reported no/little or mild disease; the impact of psoriasis on daily life increased with disease severity (p=0.0001 for trend). Those with psoriasis reported significantly more frequent mental distress or mild to severe depression than those without psoriasis. Psoriasis was also significantly associated with obesity and former smoking status. CONCLUSIONS: Psoriasis is a large public health problem. Further characterizing psoriasis from a public health perspective will require better survey questions and inclusion of these questions in national surveys.

The Effect of Gynecologic Oncologist Availability on Ovarian Cancer Mortality.

AIM: To determine the association between the distribution of gynecologic oncologist (GO) and population-based ovarian cancer death rates. MATERIALS AND METHODS: Data on ovarian cancer incidence and mortality in the United States (U.S.) was supplemented with U.S. census data, and analyzed in relation to practicing GOs. GO locations were geocoded to link association between county variables and GO availability. Logistic regression was used to measure areas of high and low ovarian cancer mortality, adjusting for contextual variables. RESULTS: Practicing GOs were unevenly distributed in the United States, with the greatest numbers in metropolitan areas. Ovarian cancer incidence and death rates increased as distance to a practicing GO increased. A relatively small number (153) of counties within 24 miles of a GO had high ovarian cancer death rates compared to 577 counties located 50 or more miles away with high ovarian cancer death rates. Counties located 50 or more miles away from a GO practice had an almost 60% greater odds of high ovarian cancer mortality compared to those with closer practicing GOs (OR 1.59, 95% CI 1.18-2.15). CONCLUSION: The distribution of GOs across the United States appears to be significantly associated with ovarian cancer mortality. Efforts that facilitate outreach of GOs to certain populations may increase geographic access. Future studies examining other factors associated with lack of GO access (e.g. insurance and other socioeconomic factors) at the individual level will assist with further defining barriers to quality ovarian cancer care in the United States.