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Various surgical options have been described for the treatment of aberrant subclavian arteries and an associated Kommerell diverticulum.Between 1999 and 2019, 43 patients underwent a repair, comprising 26 (61%) endovascular and 17 (39%) open approaches. The endovascular approach consisted of initial subclavian revascularization followed by thoracic endovascular aortic repair. The open approach included total arch replacement (12%) and reverse hemiarch repair with left thoracotomy (53%) or right thoracotomy (35%). The perioperative and long-term outcomes were retrospectively reviewed.No mortality occurred in the endovascular group, whereas there was 1 (6%) in the open approach group. Patients in the endovascular group demonstrated a shorter hospital stay (3.5 days vs 10.0 days; P = .001) and less frequent prolonged mechanical ventilation (0% vs 24%; P = .019), with a lower occurrence of pneumonia (0% vs 24%; P = .019). Among patients who had the endovascular approach, shrinkage of Kommerell diverticulum or aberrant vessel origin was seen in 96%. Furthermore, relief of dysphagia was confirmed in 92% (12/13), including patients without Kommerell diverticulum (n = 3) after endovascular repair. The cumulative incidence of treatment failure or aortic reintervention at 7 years was 21% and 14 % in the endovascular and open approach groups, respectively (P = .62). Two (8%) patients in the endovascular group required an open reintervention. One reintervention was performed for persistent dysphagia in the setting of an untreated complete vascular ring, and the other was for persistent false lumen flow associated with aortic dissection.The treatment approach should be individualized on the basis of the aortic disease and comorbidities. The endovascular approach is a viable and effective alternative in the presence of suitable landing zones.

Many people with fibromyalgia use cannabidiol (CBD) products despite limited rigorous evidence of benefit. In the current study, we conducted a secondary analysis of a cross-sectional survey of N = 878 people with fibromyalgia to investigate naturalistic decision making around CBD product choices, use patterns, and dosing. We subgrouped participants based on use of high-THC cannabis (HTC) in the past year (yes/no) as previous studies have shown that HTC use influences CBD use patterns. The study population was largely female (93.6%), white (91.5%) and 55.5 years old on average. Participants typically purchased CBD products online or at dispensaries, with purchasing driven by personal research (63%) rather than endorsement from medical professionals (16%). Overall, tinctures and topicals were the most common administration routes endorsed. However, participants in the past-year HTC group used inhalation routes far more frequently than those who did not (39.8% vs 7.1%). Among participants using CBD tinctures or edibles, the average dose per session was 16 mg and 24 to 27 mg per day, although approximately one-third of participants did not know what dose of CBD they used. Participants using both inhalation and non-inhalation administration routes reported greater symptom relief than those using non-inhalation routes alone. However, there was no consistent relationship between CBD dose and reported effects, possibly due to expectancy effects around CBD products or interindividual variability. Our granular investigation reveals variability of CBD product dosing practices for fibromyalgia, and how past-year HTC use influences CBD product use. Future clinical trials should investigate the potential benefits of low-dose (50mg) botanical CBD products. PERSPECTIVE: This article shows that past-year HTC use strongly influences how people with fibromyalgia choose and use CBD products. Participants typically used50 mg/d of CBD, and there was no relationship between higher CBD dose and reported therapeutic benefit. Future clinical trials should investigate therapeutic benefits of low dose CBD.

People report substituting cannabis for pain medications, but whether cannabidiol (CBD) is used similarly remains unknown. CBD products can be CBD alone (isolate), hemp extract (containing0.3% Δ-9-tetrahydrocannabinol [THC], other cannabinoids, and terpenes), or CBD-cannabis (containing0.3% THC). In a secondary analysis from a cross-sectional survey, we examined substitution patterns among n = 878 individuals with fibromyalgia who currently used CBD. We sub-grouped participants by most commonly used CBD product (CBD isolate, hemp, CBD-cannabis, no preference) and whether they substituted CBD for medications. We investigated rationale for substituting, substitution-driven medication changes, CBD use patterns, and changes in pain-related symptoms (eg, sleep, anxiety). The study population was 93.6% female and 91.5% Caucasian, with an average age of 55.5 years. The majority (n = 632, 72.0%) reported substituting CBD products for medications, most commonly NSAIDs (59.0%), opioids (53.3%), gabapentanoids (35.0%), and benzodiazepines (23.1%). Most substituting participants reported decreasing or stopping use of these pain medications. The most common reasons for substitution were fewer side effects and better symptom management. Age, hemp products, past-year use of marijuana, and higher somatic burden were all associated with substituting (P's ≤ .05). Those who substituted reported larger improvements in health and pain than those who did not. Participants using CBD-cannabis reported significantly more substitutions than any other group (P's ≤ .001) and larger improvements in health, pain, memory, and sleep than other subgroups. This widespread naturalistic substitution for pain medications suggests the need for more rigorous study designs to examine this effect. PERSPECTIVE: This article shows that people with fibromyalgia are deliberately substituting CBD products for conventional pain medications despite the dearth of evidence suggesting CBD products may be helpful for fibromyalgia. CBD's medication-sparing and therapeutic potential should be examined in more rigorous study designs.

Cognitive dysfunction is a common fibromyalgia (FM) symptom and can impact on the daily lives of those affected. We investigated whether within-day pain intensity ratings were associated with contemporaneous objective and subjective measures of cognitive function and whether within-day increases in pain intensity preceded increases in cognitive dysfunction or vice versa. Inclusion of a non-FM group allowed us to examine whether effects were specific to FM. Fifty people with FM and 50 non-FM controls provided 7 days of data. Cognitive tests (processing speed and working memory) and ecological momentary assessments (pain intensity and self-reported cognitive functioning) were conducted ×5/day. Three-level multilevel models examined contemporaneous and within-day 1-lag pain intensity-cognitive functioning associations. Interaction terms assessed possible moderating effects of FM status. Momentary increase in pain was associated with increased self-reported cognitive dysfunction, more strongly so for those with FM (B = 0.27, 95% confidence interval 0.22-0.32; non-FM B = 0.17, 95% confidence interval 0.10-0.23). For the FM group, higher pain was associated with longer processing speed; for the non-FM group, higher pain was associated with shorter processing speed. Pain increase did not precede change in subjective or objective cognitive function in the FM group, but reduction in working memory preceded increase in pain intensity. This finding warrants further research attention and, if replicated, could hold prognostic and/or therapeutic potential.

Objective: We describe the process of working with stakeholders with multiple sclerosis (MS) to develop a web-based multisymptom self-management program to address chronic pain, fatigue, and/or depressive symptoms. The results of a pilot trial to test the feasibility and effects of the program are presented. Method: The first study phase involved the development of a web-based symptom self-management program. The second phase involved a single-arm pilot trial (N = 20) of unguided website use for 12 weeks in adults with MS and elevated levels of chronic pain, fatigue, and/or depressed mood. Results: A web-based symptom self-management program, My MS Toolkit, was developed and released for public use in 2019. The results from the pilot trial showed that on average, participants accessed the website 5.4 times, spending about 7 min on the site per visit. Eighty percent rated intervention-related changes in activity limitations, symptoms, emotions, and overall quality of life as either "somewhat" or "moderately" better. Although there were no significant improvements on outcome measures, of those who screened positive for the outcome of interest (i.e., showed a clinically elevated level of that symptom), clinically significant improvement was seen in 37.5% for fatigue, 45.5% for pain, and 40% for depressive symptoms. Conclusions: My MS Toolkit is an accessible, stakeholder-informed, web-based MS symptom self-management program that demonstrated a clinically significant positive impact on symptoms in a proportion of participants. More research is needed to further examine the effects of this program and elucidate who is most likely to benefit from this type of self-guided intervention. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Objective Perceived cognitive dysfunction in fibromyalgia (FM), "fibrofog," is common. Prior laboratory-based studies have limited our understanding of cognitive function in FM in daily life. The objective of this study was to explore levels of subjective and objective cognitive functioning and the association between subjective and objective aspects of cognition in people with and without FM in the lived environment. Methods Participants (n = 50 adults with FM; n = 50 adults without FM, matched for age, sex, and education) completed baseline measures of subjective and objective cognitive functioning (NIH Toolbox). They also completed ecological momentary assessments of cognitive clarity and speed and tests of processing speed and working memory, via a smart phone app, 5×/day for 8 days. Results On baseline objective measures, the FM group demonstrated poorer cognitive functioning across 3 NIH Toolbox tests. There were no strong correlations between subjective and objective cognitive functioning in both the FM and control groups. In the lived environment, the FM group demonstrated poorer subjective cognition and objective working memory; groups did not differ on processing speed. Momentary ratings of subjective cognitive dysfunction were significantly related to changes in objective processing speed but not working memory, with no group differences. Conclusion Findings indicate worse laboratory-based and ambulatory subjective and objective cognitive function for those individuals with FM compared to those without FM. Similar associations between measures of subjective and objective cognitive functioning for the groups suggest that people with FM are not overstating cognitive difficulties. Future research examining contributors to ambulatory fibrofog is warranted.

Internet-based interventions for chronic pain have demonstrated efficacy and may address access barriers to care. Participant characteristics have been shown to affect engagement with these programs; however, limited information is available about the relationship between participant characteristics and engagement with internet-based programs for self-management of chronic pain. The current study examined relationships between demographic and clinical characteristics and engagement with the Pain EASE program, a self-directed, internet-based cognitive behavioral therapy intervention for veterans with chronic low back pain (cLBP). Veterans with cLBP were enrolled in a 10 week trial of the Pain EASE program. Engagement measures included the number of logins, access to coping skill modules, and completed study staff-initiated weekly check-in calls. Regression analyses were conducted to identify significant predictors of engagement from hypothesized predictors (e.g., race/ethnicity, age, depressive symptom severity, and pain interference). Participants (N = 58) were 93% male, 60.3% identified as White, and had a mean age of 54.5 years. Participants logged into the program a median of 3.5 times, accessed a median of 2 skill modules, and attended a median of 6 check-in calls. Quantile regression revealed that, at the 50th percentile, non-White-identified participants accessed fewer modules than White-identified participants (p = .019). Increased age was associated with increased module use (p = .001). No clinical characteristics were significantly associated with engagement measures. White-identified race/ethnicity and increased age were associated with greater engagement with the Pain EASE program. Results highlight the importance of defining and increasing engagement in internet-delivered pain care.

Objective\ud Exposure to early adversity carries long term harmful consequences for children's health and development. This study aims to 1) estimate the prevalence of childhood adversity for Australian children from infancy to 10–11 years, and 2) document inequalities in the distribution of adversity according to socioeconomic position (SEP), Indigenous status, and ethnicity.\ud \ud Methods\ud Adversity was assessed every 2 years from 0–1 to 10–11 years in the nationally representative birth cohort of the Longitudinal Study of Australian Children (N = 5107). Adversity included legal problems; family violence; household mental illness; household substance abuse; harsh parenting; parental separation/divorce; unsafe neighborhood; family member death; and bullying (from 4 to 5 years). Adversities were examined individually and summed for a measure of multiple adversity (2+ adverse experiences).\ud \ud Results\ud By 10–11 years, 52.8% (95% confidence interval [CI] 51.0–54.7) of children had been exposed to 2 or more adversities. When combined with low SEP, children from ethnic minority and from Indigenous backgrounds had 4 to 8 times the odds of exposure to 2 or more adversities than children from higher SEP Anglo-Euro backgrounds, respectively (odds ratio [OR] 4.3, 95% CI 2.8–6.6 and OR 8.1, 95% CI 4.4–14.8). Ethnic minority and Indigenous children from higher SEP backgrounds had increased odds of exposure to multiple adversity than similarly advantaged Anglo-Euro children (OR 1.8, 95% CI 1.4–2.3 and OR 2.3, 95% CI 1.3–4.3, respectively).\ud \ud Conclusions\ud Addressing early adversity is a significant opportunity to promote health over the life course, and reduce health inequalities experienced by marginalized groups of children.

The high prevalence of obesity among Black Americans warrants additional investigation into its relationship with socioeconomic position (SEP), sex, and ethnicity. This cross-sectional study utilizes 2001-2003 data from the National Survey of American Life, a nationally representative sample of 3570 African-Americans and 1621 Caribbean-Blacks aged 18 years and older. Multivariate logistic regression models stratified by ethnicity and sex describe the independent associations between obesity and multilevel socioeconomic factors after adjustment for age, other SEP measures at the individual, family and neighborhood levels, and health behaviors such as physical activity, alcohol intake, and smoking. A positive relationship was observed between obesity and family income among African-American and Caribbean-Black men. Receipt of public assistance was a strongly associated factor for obesity in Caribbean-Black men and women. Among African-American women, inverse relationships were observed between obesity and education, occupation, and family income; residence within a neighborhood with a supermarket also decreased their odds of obesity. Residence in a neighborhood with a park decreased the odds of obesity only among African-American men, whereas residence in a neighborhood with a supermarket decreased the odds of obesity among Caribbean-Black men. The social patterning of obesity by individual, household, and neighborhood socioeconomic resources differs for African-American and Caribbean-Black men and women within these cross-sectional analyses; an appreciation of these differences may be a prerequisite for developing effective weight control interventions and policies for these two populations.

Summary Stem cell-based transplantation therapies offer hope for currently untreatable retinal degenerations; however, preclinical progress has been largely confined to rodent models. Here, we describe an experimental platform for accelerating photoreceptor replacement therapy in the nonhuman primate, which has a visual system much more similar to the human. We deployed fluorescence adaptive optics scanning light ophthalmoscopy (FAOSLO) to noninvasively track transplanted photoreceptor precursors over time at cellular resolution in the living macaque. Fluorescently labeled photoreceptors generated from a CRX+/tdTomato human embryonic stem cell (hESC) reporter line were delivered subretinally to macaques with normal retinas and following selective ablation of host photoreceptors using an ultrafast laser. The fluorescent reporter together with FAOSLO allowed transplanted photoreceptor precursor survival, migration, and neurite formation to be monitored over time in vivo. Histological examination suggested migration of photoreceptor precursors to the outer plexiform layer and potential synapse formation in ablated areas in the macaque eye., Highlights • Longitudinal imaging of single fluorescently tagged donor photoreceptors in primates • Donor photoreceptor migration and neurite outgrowth were detected in the living eye • In a photoreceptor ablation model, donor photoreceptors migrated to the OPL • Donor photoreceptors structurally made synaptic connections with host bipolar cells, In this article, David Williams and colleagues demonstrate the capability of fluorescence adaptive optics imaging that allows longitudinal tracking of the behavior of transplanted photoreceptors at a single-cell level in living primate eyes. This study shows transplanted photoreceptors migrated to the outer plexiform layer through the laser lesion sites and often extended neurites containing presynaptic proteins toward the host inner nuclear layer.

Aims The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network initiated a second observational cohort study-the Symptom Patterns Study (SPS)-to further investigate the underlying pathophysiology of Urologic Chronic Pelvic Pain Syndrome (UCPPS) and to discover factors associated with longitudinal symptom changes and responses to treatments. Methods This multisite cohort study of males and females with UCPPS features a run-in period of four weekly web-based symptom assessments before a baseline visit, followed by quarterly assessments up to 36 months. Controls were also recruited and assessed at baseline and 6 months. Extensive clinical data assessing urological symptoms, nonurological pain, chronic overlapping pain syndromes, and psychosocial factors were collected. Diverse biospecimens for biomarker and microbiome studies, quantitative sensory testing (QST) data under multiple stimuli, and structural and functional neuroimaging scans were obtained under a standardized protocol. Results Recruitment was initiated (July 2015) and completed (February 2019) at six discovery sites. A total of 620 males and females with UCPPS and 73 Controls were enrolled, including 83 UCPPS participants who re-enrolled from the first MAPP Network cohort study (2009-2012). Baseline neuroimaging scans, QST measures, and biospecimens were obtained on 578 UCPPS participants. The longitudinal follow-up of the cohort is ongoing. Conclusions This comprehensive characterization of a large UCPPS cohort with extended follow-up greatly expands upon earlier MAPP Network studies and provides unprecedented opportunities to increase our understanding of UCPPS pathophysiology, factors associated with symptom change, clinically relevant patient phenotypes, and novel targets for future interventions.

As many as one third of patients undergoing minimally invasive thoracic surgery and one half undergoing thoracotomy will have chronic pain, defined as pain lasting 2 to 3 months. There is limited information regarding predictors of chronic pain and even less is known about its impact on health-related quality of life, known as pain interference. Currently, there is a focus on decreased opioid prescribing after surgery. Interestingly, thoracic surgical patients are the least likely to be receiving opioids before surgery and have the highest rate of new persistent opioid use after surgery compared with other surgical cohorts. These studies of opioid use have identified important predictors of new persistent opioid use, but their findings are limited by failing to correlate opioid use with pain. The objectives of this invited review are to present the findings of pertinent studies of chronic pain and opioid use after thoracic surgery, "where we are," and to discuss gaps in our knowledge of these topics and opportunities for research to fill those gaps, "where we need to go."

Objectives: The metabolic syndrome (MetS) refers to a cluster of interrelated physiological characteristics that are associ­ated with an increased risk of cardiovascular disease and diabetes. While the clinical usefulness of the MetS has been the subject of controversy for years, increasingly sophis­ticated methods are being used to measure the concept. Participants: Study of community health center patients who were not diabetic; study group was evenly divided between Black and White adults. Methods: Structural equation modeling of MetS incorporating the effects of race/eth­nicity, racial discrimination, socioeconomic position (SEP), and selected mediating variables. Main Outcome Measure: Latent MetS score and MetS status based on the five-point scale developed by the National Cholesterol Education Panel (NCEP). Results: The largest influences on latent MetS scores were SEP (negative relationship) and male gender (higher scores for men). Two mediating variables, physical activ­ity and stress-related eating, had smaller impacts. Self-reported racial discrimination was associated with cynical hostility but did not influence the MetS level among non­diabetics. Despite higher NCEP scores and MetS prevalence rates for Blacks compared with Whites, race did not have direct effect on MetS levels when adjusted for the other characteristics in our model. Conclusions: Neither race nor self-reported racial discrimination had direct effects on MetS level in our structural model. The large effects of socioeconomic position and male gender were not mediated by the other variables in the model. Ethn Dis. 2020;30(2):331-338; doi:10.18865/ ed.30.2.331

Objectives Quantitative sensory testing may help predict treatment responses in individuals with chronic pain. Our objective was to determine whether evoked pain sensitivity at baseline predicted preferential treatment responses to either emotional awareness and expression therapy (EAET) or cognitive behavioral therapy (CBT) in individuals with fibromyalgia (FM). Methods This was a secondary analysis of a previous randomized clinical trial, in which individuals with FM were randomized to EAET, CBT, or Education as a control intervention. Only females who completed baseline and post-treatment assessments were analyzed (n=196). The primary outcome was change in overall clinical pain severity from pretreatment to posttreatment, and the primary predictor of interest was pressure pain tolerance at baseline. Results Among patients with low pain tolerance at baseline (n=154), both EAET and CBT led to small but significant improvements in clinical pain severity (CBT mean=0.66, 95% confidence interval [0.24-1.07]; EAET mean=0.76 [0.34-1.17]). Conversely, in patients with normal pain tolerance (n=42), there was no significant improvement in clinical pain after CBT (0.13 [-0.88 to 1.14]), a small improvement after FM Education (0.81 [0.14-1.48]), but a much larger and statistically significant improvement after EAET (2.14 [1.23-3.04]). Discussion Normal levels of pressure pain tolerance at baseline predicted greater improvement in clinical pain severity after EAET than CBT. Quantitative sensory testing may provide insights about individual responses to psychologically based therapies for individuals with chronic pain.

Objective Self-reported "sleep quality" often is assessed in epidemiologic studies. However, the bases for variation in sleep quality is not fully understood. We quantified the extent to which subjective sleep quality was related to sleep disorders and sleep characteristics among 795 African American adults. Method Between 2012 and 2016, participants underwent home sleep apnea testing and 1-week actigraphy (estimating sleep duration, efficiency, fragmentation, latency). Sleep quality, insomnia and restless legs syndrome symptoms, sleepiness, and physician diagnosis of sleep disorders were self-reported. We fit linear regression models to determine the extent to which subjective and objective sleep measures as well as depressive symptoms and anxiety were related to subjective sleep quality. Results After adjustment for covariates, worse sleep quality scores were associated with insomnia and restless legs syndrome symptoms, sleep apnea, physician diagnosis of a sleep disorder, and actigraphy-based fragmented sleep, lower sleep efficiency, and shorter sleep duration. Insomnia symptoms explained the most variance in subjective sleep quality, 21%. Other sleep measures each explained 3% to 7% and psychosocial factors explained 8% to 9% of the variance in subjective sleep quality after adjustment for confounders. Conclusions The weak associations of sleep quality with sleep disorders and objectively measured sleep disturbances are consistent with concepts of "sleep health" as a multidimensional construct. Sleep quality is a patient-centered outcome that provides unique information over objective measurements of sleep disturbances.

Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition carrying substantial psychosocial burden. Psychological treatment for IC/BPS is little studied, and there are barriers to its use in clinical management. Whether psychological treatments benefit patients with IC/BPS is unclear and we do not know whether such treatments would meet patient needs. Aims: Incorporating patient-reported needs and acknowledging diversity in pain experiences can inform patient-centered interventions for IC/BPS. This project characterized the experience of living with IC/BPS and patient perceptions of needs in its treatment, with the goal of informing patient-centered treatment for IC/BPS. Methods: Using both quantitative and qualitative methods, 27 females with IC/BPS participated in a focus group and completed validated self-report assessments evaluating urinary symptoms, pain, and emotional functioning. Focus groups were audio recorded and transcribed and then coded and analyzed using an iterative inductive/deductive approach. Linear regression models evaluated the relationship between psychological functioning and symptom severity. Results: We conducted six focus groups between August and December 2017. Five major themes emerged from qualitative analysis: managing physical symptoms, emotional symptoms, impact on daily life and socio-contextual factors, responding to illness, and addressing needs in treatment. The physiological and emotional consequences of IC/BPS were reported, highlighting their impact on interpersonal relationships and challenges in obtaining appropriate treatment for IC/BPS. Quantitative analysis showed that depression levels were significantly associated with worsened IC/BPS symptomology, after controlling for known confounding factors. Conclusion: Individuals with IC/BPS could benefit from tailored psychological interventions focusing on pain management, emotion regulation, communications skills, along with sexual dysfunction and intimacy fears.

Historically, a variety of non–dissection proximal aortic pathologies with suitable anatomy have been treated with thoracic endovascular aortic repair (TEVAR) with high technical success rates. However, TEVAR use for acute type A aortic dissection has been extremely limited due to the unique challenging anatomic and clinical features and the lack of specifically-designed endoprostheses. These features include: proximity of the aortic valve, coronary arteries, and supra-aortic vessels, related aortic insufficiency, diffusely dilated aorta diameter, entry tear extension into the aortic root and/or aortic arch, the dissection involvement of supra-aortic vessels, high degrees of ascending aortic curvature and notable length discrepancies between the greater and lesser curvatures, and tissue fragility at prosthesis-tissue transition zones. Additionally, the presence of patent coronary artery bypass grafting conduits on the ascending aorta is another factor precluding endovascular options and hybrid surgical and endovascular approaches may be considered. In contrast, early feasibility clinical trials of investigational devices specifically designed to treat type A aortic dissections have been currently underway. In our opinion, the location and extent of intimal tears are quite variable and only a minority of patients with type A aortic dissection are deemed suitable candidates for ascending TEVAR. On the contrary, combined application of aortic arch endograft, as demonstrated in the present report, likely increases TEVAR candidacy as well as procedural success rates.

Persistent fatigue is common among military servicemembers returning from deployment, especially those with a history of mild traumatic brain injury (mTBI). The purpose of this study was to characterize fatigue following deployment using the Multidimensional Fatigue Inventory (MFI), a multidimensional self-report instrument. The study was developed to test the hypothesis that if fatigue involves disrupted effort/reward processing, this should manifest as altered basal ganglia functional connectivity as observed in other amotivational states.Twenty-eight current and former servicemembers were recruited and completed the MFI. All 28 participants had a history of at least one mTBI during deployment. Twenty-six participants underwent resting-state functional MRI. To test the hypothesis that fatigue was associated with basal ganglia functional connectivity, the investigators measured correlations between MFI subscale scores and the functional connectivity of the left and right caudate, the putamen, and the globus pallidus with the rest of the brain, adjusting for the presence of depression.The investigators found a significant correlation between functional connectivity of the left putamen and bilateral superior frontal gyri and mental fatigue scores. No correlations with the other MFI subscales survived multiple comparisons correction.This exploratory study suggests that mental fatigue in military servicemembers with a history of deployment with at least one mTBI may be related to increased striatal-prefrontal functional connectivity, independent of depression. A finding of effort/reward mismatch may guide future treatment approaches.

ObjectiveIdiopathic macular telangiectasia (MacTel) is considered primarily a vascular disease affecting juxtafoveal retinal capillaries. However, recent evidence suggests that neuronal changes may occur early in disease development. We used high-resolution adaptive optics retinal imaging to elucidate the foveal cone photoreceptor changes at a cellular level in patients with MacTel.Methods and analysisWe used adaptive optics scanning light ophthalmoscopy (AOSLO) to evaluate the foveal cone photoreceptors in the less-affected eye of patients with asymmetric MacTel. AOSLO images of cone photoreceptors were obtained in a 4°×4° area centred on the foveola. Individual cone positions were identified within a 2°×2° area centred on the fovea, using semiautomatic cone marking software with manual correction, permitting calculation of a map of cone density.ResultsIn all participants, one eye was affected with MacTel, the fellow eye was clinically normal or near normal, with visual acuity of 20/25 or better and subtle angiographic leakage. The foveal cone mosaics were continuous with tight packing and cones exhibited normal reflectivity. However, cone density was significantly lower for all participants (mean=80 733 cones/mm2) within 0.5° than the cone density previously reported for normal eyes.ConclusionsFoveal cone density is lower than normal in the clinically less-affected eyes of patients with asymmetric MacTel. This suggests that cone photoreceptor loss may precede classic obvious vascular changes in idiopathic MacTel.

OBJECTIVES: Limited research suggests commonalities between urologic chronic pelvic pain syndromes (UCPPS) and other non-urologic chronic overlapping pain conditions (COPCs) including fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome. The goal of this case-control study was to examine similarities and differences between UCPPS and these other COPCs. METHODS: As part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network, we examined 1,039 individuals with UCPPS (n = 424), non-urologic COPCs (n = 200), and healthy controls (n = 415). Validated standardized measures were used to assess urological symptoms, non-urological pain symptoms, and psychosocial symptoms and traits. RESULTS: Participants with UCPPS had more urologic symptoms than non-urologic COPCs or healthy controls (p < 0.001); non-urological COPC group also had significantly worse urological symptoms than healthy controls (p < 0.001). Participants with non-urological COPCs reported more widespread pain than those with UCPPS (p < 0.001), yet both groups had similarly increased symptoms of anxiety, depression, negative affect, perceived stress, neuroticism, and lower levels of extraversion than healthy controls (p < 0.001). Participants with UCPPS with and without COPCs reported more catastrophizing than those with non-urological COPCs (p < 0.001). DISCUSSION: Findings are consistent with the hypothesis of common underlying biopsychosocial mechanisms and can guide the comprehensive assessment and treatment of these conditions regardless of the primary site of pain or diagnosis. Heightened catastrophizing in UCPPS should be examined to inform psychosocial interventions and improve patient care.

The aim of this study was to describe the degree of self-stigma in patients with schizophrenia across three Latin-Americans countries (Bolivia, Chile and Peru). The study included 253 outpatients that were assessed using the Internalized Stigma of Mental Illness Scale (ISMI). The results show that 48.7% of patients from Bolivia report high internalized stigma compared to 38.6% from Chile and 28.6% from Peru. There were no statistically significant differences in ISMI mean total scores for country (p = 0.057), however, there were significant differences on two subscales: alienation and social withdrawal for which Bolivia had the highest scores. In conclusion, even though these countries share several common cultural characteristics, there are also some differences between them on patients' self-stigma.

Objectives: To examine the association of perceived discrimination with participant retention and diabetes risk among American Indians and Alaska Natives. Methods: Data were drawn from the Special Diabetes Program for Indians–Diabetes Prevention Demonstration Project ( N = 2553). Results: Perceived discrimination was significantly and negatively associated with short-term and long-term retention and diabetes risk without adjusting. After controlling for socioeconomic characteristics and clinical outcomes, perceived discrimination was not associated with retention but was significantly associated with less improvement in body mass index (BMI) and high-density lipoprotein (HDL) cholesterol. Every unit increase in the perceived discrimination score was associated with 0.14 kg/m2 less BMI reduction (95% CI: [0.02, 0.26], p = 0.0183) and 1.06 mg/dl lower HDL at baseline (95% CI: [0.36, 1.76], p = 0.0028). Discussion: Among racialized groups, improving retention and health in lifestyle interventions may require investigating perceived discrimination and the broader context of structural racism and colonialism.

AIM: We examined prevalence and factors associated with receiving perceived helpful alcohol use disorder (AUD) treatment, and persistence in help-seeking after earlier unhelpful treatment.METHODS: Data came from 27 community epidemiologic surveys of adults in 24 countries using the World Health Organization World Mental Health surveys (n = 93,843). Participants with a lifetime history of treated AUD were asked if they ever received helpful AUD treatment, and how many professionals they had talked to up to and including the first time they received helpful treatment (or how many ever, if they had not received helpful treatment).RESULTS: 11.8% of respondents with lifetime AUD reported ever obtaining treatment (n = 9378); of these, 44% reported that treatment was helpful. The probability of obtaining helpful treatment from the first professional seen was 21.8%; the conditional probability of subsequent professionals being helpful after earlier unhelpful treatment tended to decrease as more professionals were seen. The cumulative probability of receiving helpful treatment at least once increased from 21.8% after the first professional to 79.7% after the seventh professional seen, following earlier unhelpful treatment. However, the cumulative probability of persisting with up to seven professionals in the face of prior treatments being unhelpful was only 13.2%.CONCLUSION: Fewer than half of people with AUDs who sought treatment found treatment helpful; the most important factor was persistence in seeking further treatment if a previous professional had not helped. Future research should examine how to increase the likelihood that AUD treatment is found to be helpful on any given contact.

All retina-based vision restoration approaches rely on the assumption that photoreceptor loss does not preclude reactivation of the remaining retinal architecture. Whether extended periods of vision loss limit the efficacy of restorative therapies at the retinal level is unknown. We examined long-term changes in optogenetic responsivity of foveal retinal ganglion cells (RGCs) in non-human primates following localized photoreceptor ablation by high intensity laser exposure. By performing fluorescence adaptive optics scanning light ophthalmoscopy (AOSLO) of RGCs expressing both the calcium indicator GCaMP6s and the optogenetic actuator ChrimsonR, it was possible to track optogenetic mediated calcium responses in deafferented RGCs over time. Fluorescence fundus photography revealed a 40% reduction in ChrimsonR fluorescence in RGCs lacking photoreceptor input over the three weeks following photoreceptor ablation. Despite this, in vivo imaging revealed good cellular preservation of RGCs 3 months after the loss of photoreceptor input, and histology confirmed good structural preservation at 2 years. Optogenetic responses of RGCs in primate persisted for at least one year after the loss of photoreceptor input, with a sensitivity index similar to optogenetic responses recorded in intact retina. These results are promising for all potential therapeutic approaches to vision restoration that rely on preservation and reactivation of RGCs.

Altered brain structure and function is evident in adults with multisite chronic pain. Although many such adults trace their pain back to childhood, it has been difficult to disentangle whether central nervous system alterations precede or are consequences of chronic pain. If the former is true, aberrant brain activity may identify children vulnerable to developing chronic pain later in life. We examined structural and functional brain magnetic resonance imaging metrics in a subset of children from the first two assessments of the Adolescent Brain and Cognitive Development (ABCD) Study. Children (ages 9-10) who were pain-free at baseline and then developed multisite pain one year later (n=115) were matched to control children who were pain-free at both timepoints (n=230). We analyzed brain structure (cortical thickness and gray matter volume) and function (spontaneous neural activity and functional connectivity). Results were deemed significant at the cluster level p < 0.05 false discovery rate corrected for multiple comparisons. At baseline, children who subsequently developed multisite pain had increased neural activity in superior parietal/primary somatosensory and motor cortices and decreased activity in the medial prefrontal cortex. They also exhibited stronger functional connectivity between the salience network, somatosensory and default mode network regions. No significant differences in brain structure were observed. Increased neural activity and functional connectivity between brain regions, consistent to that seen in adults with chronic pain, exist in children prior to developing multisite pain. These findings may represent a neural vulnerability to developing future chronic pain.

Background and Aims Mutations in IL10 or the IL10 receptor lead to very early onset [VEO] inflammatory bowel disease [IBD], a life-threatening disease which is often unresponsive to conventional medication. Recent studies have demonstrated that defective IL-10 receptor signalling in innate immune cells is a key driver of severe intestinal inflammation in VEO-IBD. Specifically, IL10 unresponsiveness of macrophages, which govern the tight balance between pro- and anti-inflammatory responses in the intestinal system, plays a central role in the events leading to excessive inflammatory responses and the development of IBD. Methods and Results We here evaluated haematopoietic stem cell gene therapy in a VEO-IBD mouse model and demonstrated that the therapeutic response closely correlates with gene correction of the IL10 signalling pathway in intestinal macrophages. This finding prompted us to evaluate the therapeutic efficacy of macrophage transplantation in the Il10rb-/- VEO-IBD mouse model. A 6-week regimen employing a combination of depletion of endogenous hyperinflammatory macrophages followed by intraperitoneal administration of wild-type [WT] macrophages significantly reduced colitis symptoms. Conclusions In summary, we show that the correction of the IL10 receptor defect in macrophages, either by genetic therapy or transfer of WT macrophages to the peritoneum, can ameliorate disease-related symptoms and potentially represent novel treatment approaches for VEO-IBD patients.

Evidence of an association between psychosocial stress and mortality continues to accumulate. However, despite repeated calls in the literature for further examination into the physiological and behavioral pathways though which stress affects health and mortality, research on this topic remains limited. This study addresses this gap by employing a counterfactual-based mediation analysis of eight behavioral, biological, and psychological pathways often hypothesized to play a role in the association between stress and health. First, we calculated the survival rate of all-cause mortality associated with cumulative psychosocial stress (high vs. low/moderate) using random effects accelerated failure time models among a sample of 7108 adults from the Midlife in the United States panel study. Then, we conducted a multiple mediator mediation analysis utilizing a counterfactual regression framework to determine the relative contributions of each mediator and all mediators combined in the association between stress and mortality. Exposure to high psychosocial stress was associated with a 0.76 times reduced survival rate over the follow-up period 1995–2015, while adjusting for age, sex, race, income, education, baseline health, and study design effects. The mediators accounted for 49% of this association. In particular, smoking, sedentary behavior, obesity/BMI, and cardiovascular disease displayed significant indirect effects and accounted for the largest reductions in the total effect of stress on mortality, with natural indirect effects of 14%, 12%, 11%, and 4%, respectively. In conclusion, traditional behavioral and biological risk factors play a significant role in the association between psychosocial stress and mortality among middle and older adults in the US context. While eliminating stress and the socioeconomic disparities that so often deliver people into high-stress scenarios should be the ultimate goal, public health interventions addressing smoking cessation, physical activity promotion, and cardiovascular disease treatment may pay dividends for preventing premature mortality in the near-term. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-020-00319-5.

Objective To examine the impact of educational materials for chronic overlapping pain conditions (COPCs), the feasibility of delivering materials online, and to explore its impact on self-reported self-management applications at 3-month follow-up. Design Prospective cohort study Setting Online Subjects Individuals from a university-wide active research repository with ≥1 coded diagnostic COPC by ICD-9/10 in the medical record. Methods We determined the number of COPCs per participant as indicated by diagnostic codes in the medical record. Consenting participants completed self-report questionnaires and read educational materials. We assessed content awareness and knowledge pre- and post-exposure to education. Comprehension was assessed via embedded questions in reading materials in real time. Participants then completed assessments regarding concept retention, self-management engagement, and pain-related symptoms at 3-months. Results N = 216 individuals enrolled, with 181 (84%) completing both timepoints. Results indicated that participants understood materials. Knowledge and understanding of COPCs increased significantly after education and was retained at 3-months. Patient characteristics suggested the number of diagnosed COPCs was inversely related to age. Symptoms or self-management application did not change significantly over the 3-month period. Conclusions The educational materials facilitated teaching of key pain concepts in self-management programs, which translated easily into an electronic format. Education alone may not elicit self-management engagement or symptom reduction in this population; however, conclusions are limited by the study’s uncontrolled design. Education is likely an important and meaningful first step in comprehensive COPC self-management.

Evidence-based psychotherapies for fibromyalgia (FM) are often grounded in the BioPsychoSocial perspective. The three therapies to be reviewed here are Cognitive-Behavioral Therapy (CBT), Acceptance and Commitment Therapy (ACT), and Emotional Awareness and Expression Therapy (EAET). Each of these therapies is based upon known principles of cognitive and behavioral change and can be applied either to influence factors known to affect pain perception (e.g., sensory, emotional, cognitive) or to facilitate engagement in salient functional activities. This chapter provides a description of each form of therapy including its orientation, rationale, approaches for using the therapy, and an overview of the evidence supporting the use of each form of therapy in the treatment of FM.

Previous research suggests that stressors may trigger the onset of acute cardiovascular disease (CVD) events within hours to days, but there has been limited research around sociopolitical events such as presidential elections. Among adults ≥18 y of age in Kaiser Permanente Southern California, hospitalization rates for acute CVD were compared in the time period immediately prior to and following the 2016 presidential election date. Hospitalization for CVD was defined as an inpatient or emergency department discharge diagnosis of acute myocardial infarction (AMI) or stroke using International Classification of Diseases, 10th revision codes. Rate ratios (RR) and 95% confidence intervals (CIs) were calculated comparing CVD rates in the 2 d following the 2016 election to rates in the same 2 d of the prior week. In a secondary analysis, AMI and stroke were analyzed separately. The rate of CVD events in the 2 d after the 2016 presidential election (573.14 per 100,000 person-years [PY]) compared to the rate in the window prior to the 2016 election (353.75 per 100,000 PY) was 1.62 times higher (95% CI 1.17, 2.25). Results were similar across sex, age, and race/ethnicity groups. The RRs were similar for AMI (RR 1.67, 95% CI 1.00, 2.76) and stroke (RR 1.59, 95% CI 1.03, 2.44) separately. Transiently heightened cardiovascular risk around the 2016 election may be attributable to sociopolitical stress. Further research is needed to understand the intersection between major sociopolitical events, perceived stress, and acute CVD events.

Cannabidiol (CBD) is widely advertised as helpful for chronic pain management but research is limited. Using a cross-sectional, anonymous survey, we examined patterns of naturalistic CBD use among individuals with fibromyalgia (FM) and other chronic pain conditions. Our objective was to better understand rates of CBD use, reasons for use and discontinuation, communication with healthcare professionals about CBD, and perceptions of CBD effectiveness and safety among people with FM. After excluding incomplete surveys, our study population consisted of N = 2,701 participants with fibromyalgia, primarily in the United States. Overall, 38.1% reported never using CBD, 29.4% reported past CBD use, and 32.4% reported current CBD use. Past-year cannabis use was strongly associated with past or current CBD use. Those using CBD typically did so due to inadequate symptom relief, while those not using CBD typically cited safety concerns as their reason for not using CBD. Two-thirds of participants disclosed CBD use to their physician, although only 33% asked for physician advice on using CBD. Participants used CBD for numerous FM-related symptoms (most commonly pain), and generally reported slight to much improvement across symptom domains. Around half of participants reported side effects, which were typically minor. Our findings are limited by selection bias and our cross-sectional design, which prevents causal associations. In conclusion, CBD use is common among individuals with FM and many individuals using CBD report improvements across numerous FM-related symptoms. Our findings highlight the need for additional rigorous studies to better understand CBD's potential for FM management. Perspective This article indicates that CBD use is common among people with fibromyalgia, and the results suggest that many derive benefit from using CBD across multiple symptoms domains. Clinicians should discuss CBD use with fibromyalgia patients, and future studies are needed to rigorously assess CBD's therapeutic value for fibromyalgia symptoms.

Background Up-to-date information regarding the scope and impact of cannabinoid use among persons with MS (PwMS) is necessary to guide clinical practice and cannabinoid research. Objectives To assess utilization patterns and perceived impact of cannabinoid use among a national cohort of PwMS. Methods Data collected were part of a nationwide survey to characterize pain in PwMS. Items included questions about current/recent cannabinoid use, reasons for use, preferred THC/CBD formulations, and perceived benefits/side effects. PROMIS short-forms assessed symptom severity. Pain phenotype was assessed with the painDETECT questionnaire and FMSurvey Criteria Questionnaires. Results Among n = 1,027 respondents, 42% endorsed recent cannabinoid use, of which 18% endorsed healthcare provider guidance regarding use. PROMIS scores (except cognitive abilities), and pain centralization and neuropathic pain scores, were higher among recent/current users (each p Conclusion Cannabinoid use is common in PwMS, despite a paucity of provider guidance. The range of perceived benefits, and potential differential effects of THC and CBD, highlight the need for personalized, evidence-based guidelines regarding cannabinoid use.

Purpose The development of new approaches to human vision restoration could be greatly accelerated with the use of nonhuman primate models; however, there is a paucity of primate models of outer retina degeneration with good spatial localization. To limit ablation to the photoreceptors, we developed a new approach that uses a near-infrared ultrafast laser, focused using adaptive optics, to concentrate light in a small focal volume within the retina. Methods In the eyes of eight anesthetized macaques, 187 locations were exposed to laser powers from 50 to 210 mW. Laser exposure locations were monitored for up to 18 months using fluorescein angiography (FA), optical coherence tomography (OCT), scanning laser ophthalmoscopy (SLO), adaptive optics scanning laser ophthalmoscope (AOSLO) reflectance imaging, two-photon excited fluorescence (TPEF) ophthalmoscopy, histology, and calcium responses of retinal ganglion cells. Results This method produced localized photoreceptor loss with minimal axial spread of damage to other retinal layers, verified by in-vivo structural imaging and histologic examination, although in some cases evidence of altered autofluorescence was found in the adjacent retinal pigment epithelium (RPE). Functional assessment using blood flow imaging of the retinal plexus and calcium imaging of the response of ganglion cells above the photoreceptor loss shows that inner retinal circuitry was preserved. Conclusions Although different from a genetic model of retinal degeneration, this model of localized photoreceptor loss may provide a useful testbed for vision restoration studies in nonhuman primates. Translational relevance With this model, a variety of vision restoration methods can be tested in the non-human primate.

Snakebite disproportionally affects children living in impoverished rural communities. The WHO has recently reinstated snakebites on its list of Neglected Tropical Diseases and launched a comprehensive Strategy for the Prevention and Control of Snakebite Envenoming. In the first of a two paper series, we describe the epidemiology, socioeconomic impact and key prevention strategies. We also explore current challenges and priorities including the production and distribution of safe and effective antivenom. Revisión por pares

Background: A growing body of evidence suggests that stressors are associated with heightened cardiovascular risk within hours after the triggering event, and stress from election campaigns is associated with a heightened risk of pre-term birth. Hypothesis: Potential stress from the 2016 presidential election was associated with an increased hospitalization rate for acute myocardial infarction (AMI) in the following week. Methods: Among active members 18 years of age and older in Kaiser Permanente Southern California, AMI was defined as an inpatient hospitalization with a primary discharge diagnosis of ICD-10-CM codes I21.x or I22.x. In an ecological analysis, we calculated relative risks (RR) and 95% confidence intervals (CI) comparing rates of AMI per 100,000 person-years (PY) within one week following the date of the 2016 presidential election (risk window) to rates in the prior two weeks (control window) overall and within subgroups by age, sex, and race/ethnicity. We repeated the above analysis comparing rates of AMI within one week of the 2016 election date to rates in the prior week. Results: Compared to the rates of MI in the two weeks before the 2016 election (171.6 per 100,000 PY), the rate of AMI hospitalization in the week following election day (242.2 per 100,000 PY) was 1.41 times higher (95% CI 1.14, 1.75). (Table) Heightened AMI risk after the 2016 election was also observed among adults 55-74 years of age (RR 1.47, 95% CI 1.10, 1.98), men (RR 1.54, 95% CI 1.17, 2.02), and white individuals (RR 1.52, 95% CI 1.12, 2.06). However, there was no evidence of heterogeneity across age, sex, or race/ethnicity groups (p-values 0.98, 0.30, and 0.65, respectively). Using a one-week control window, similar results were observed. Conclusion: Increased AMI rates among subsets of the population coincident with the 2016 election is consistent with published data suggesting that acute sociopolitical stress may have adverse health effects.

International audience; Background: Prevalences of Alcohol Use Disorders (AUDs) and Mental Health Disorders (MHDs) in many individual countries have been reported but there are few cross-national studies. The WHO World Mental Health (WMH) Survey Initiative standardizes methodological factors facilitating comparison of the prevalences and associated factors of AUDs in a large number of countries to identify differences and commonalities.Methods: Lifetime and 12-month prevalence estimates of DSM-IV AUDs, MHDs, and associations were assessed in the 29 WMH surveys using the WHO CIDI 3.0.Results: Prevalence estimates of alcohol use and AUD across countries and WHO regions varied widely. Mean lifetime prevalence of alcohol use in all countries combined was 80%, ranging from 3.8% to 97.1%. Combined average population lifetime and 12-month prevalence of AUDs were 8.6% and 2.2% respectively and 10.7% and 4.4% among non-abstainers. Of individuals with a lifetime AUD, 43.9% had at least one lifetime MHD and 17.9% of respondents with a lifetime MHD had a lifetime AUD. For most comorbidity combinations, the MHD preceded the onset of the AUD. AUD prevalence was much higher for men than women. 15% of all lifetime AUD cases developed before age 18. Higher household income and being older at time of interview, married, and more educated, were associated with a lower risk for lifetime AUD and AUD persistence.Conclusions: Prevalence of alcohol use and AUD is high overall, with large variation worldwide. The WMH surveys corroborate the wide geographic consistency of a number of well-documented clinical and epidemiological findings and patterns.

Intubated pediatric patients with isolated traumatic brain injury (TBI) are a diagnostic challenge for early detection of altered cerebral physiology instigated by trauma-induced increased intracranial pressure (ICP) while preventing secondary neuronal damage (secondary insult detection) and assessing the effects of increased ICP therapeutic interventions (3% hypertonic saline [HTS]). Invasive brain tissue oxygen monitoring is guiding new intensive care unit TBI management but is not pediatric emergency department (PED) readily accessible. Objective measurements on pediatric isolated TBI-altered bihemispheric cerebral physiology and treatment effects of 3% HTS are currently lacking. Cerebral oximetry can assess increased ICP-induced abnormal bihemispheric cerebral physiology by measuring regional tissue oxygenation (rcSO2) and cerebral blood volume index (CBVI) and the mechanical cerebrospinal fluid removal effects on the increased ICP-induced abnormal bihemispheric cerebral physiology.In the PED intubated patients with isolated TBI, assessing the 3% HTS therapeutic response is solely by vital signs and limited clinical assessment skills. Objective measurements of the 3% HTS hyperosmolar effects on the PED isolated TBI patients' altered bihemispheric cerebral physiology are lacking. We believe that bihemispheric rcSO2 and CBVI could elucidate similar data on 3% HTS impact and influence in the intubated isolated TBI patients.This study aimed to analyze the effects of 3% HTS on bihemispheric rcSO2 and CBVI in intubated patients with isolated TBI.An observational, retrospective analysis of bihemispheric rcSO2 and CBVI readings in intubated pediatric patients with isolated TBI receiving 3% HTS infusions, was performed.From 2010 to 2017, 207 intubated patients with isolated TBI received 3% HTS infusions (median age, 2.9 [1.1-6.9 years]; preintubation Glasgow Coma Scale score, 7 [6-8]). The results were as follows: initial pre-3% HTS, 43% (39.5% to 47.5%; left) and 38% (35% to 42%; right) for rcSO260%, and 8 (-28 to 21; left) and -15 (-34 to 22; right) for CBVI; post-3% HTS, 68.5% (59.3% to 76%, P0.0001; left) and 62.5% (56.0% to 74.8%, P0.0001; right) for rcSO260%, and 12 (-7 to 24, P = 0.04; left) and 14 (-21 to 22, P0.0001; right) for CBVI; initial pre-3% HTS, 90% (83% to 91%; left) and 87% (82% to 92%; right) for rcSO280%, and 16.5 (6 to 33, P0.0001; left) and 16.8 (-2.5 to 27.5, P = 0.005; right) for CBVI; and post-3% HTS, 69% (62% to 72.5%, P0.0001; left) and 63% (59% to 72%, P0.0001; right) for rcSO280%, and 16.5 (6 to 33, P0.0001; left) and 16.8 (-2.5 to 27.5, P = 0.005; right) for CBVI. The following results for cerebral pathology pre-3% HTS were as follows: epidural: 85% (58% to 88.5%) for left rcSO2 and -9.25 (-34 to 19) for left CBVI, and 85.5% (57.5% to 89%) for right rcSO2 and -12.5 (-21 to 27) for CBVI; subdural: 45% (38% to 54%) for left rcSO2 and -9.5 (-25 to 19) for left CBVI, and 40% (33% to 49%) for right rcSO2 and -15 (-30.5 to 5) for CBVI. The following results for cerebral pathology post-3% HTS were as follows: epidural: 66% (58% to 69%, P = 0.03) for left rcSO2 and 15 (-1 to 21, P = 0.0004) for left CBVI, and 63% (52% to 72%, P = 0.009) for right rcSO2, and 15.5 (-22 to 24, P = 0.02) for CBVI; subdural: 63% (56% to 72%, P0.0001) for left rcSO2 and 9 (-20 to 22, P0.0001) for left CBVI, and 62.5% (48% to 73%, P0.0001) for right rcSO2, and 3 (-26 to 22, P0.0001) for CBVI. Overall, heart rate showed no significant change. Three percent HTS effect on interhemispheric rcSO2 difference10 showed rcSO260%, and subdural hematomas had the greatest reduction (P0.001). The greatest positive changes occurred in bihemispheric or one-hemispheric rcSO260% with an interhemispheric discordance rcSO210 and required the greatest number of 3% HTS infusions. For 3% HTS 15% rcSO2 change time effect, all patients achieved positive change with subdural hematomas and hemispheric rcSO2 readings60% with the shortest achievement time of 1.2 minutes (0.59-1.75; P0.001).In intubated pediatric patients with isolated TBI who received 3% HTS infusions, bihemispheric rcSO2 and CBVI readings immediately detected and trended the 3% HTS effects on the trauma-induced cerebral pathophysiology. The 3% HTS infusion produced a significant improvement in rcSO2 and CBVI readings and a reduction in interhemispheric rcSO2 discordance differences. In patients with bihemispheric or one-hemispheric rcSO2 readings60% with or without an interhemispheric discordance, rcSO210 demonstrated the greatest significant positive delta change and required the greatest numbers of 3% HTS infusions. Overall, 3% HTS produced a significant positive 15% change within 2.1 minutes of infusion, whereas heart rate showed no significant change. During trauma neuroresuscitation, especially in intubated isolated TBI patients requiring 3% HTS, cerebral oximetry has shown its functionality as a rapid adjunct neurological, therapeutic assessment tool and should be considered in the initial emergency department pediatric trauma neurological assessment and neuroresuscitation regimen.

Objective This study aimed to examine the explanatory role of health behaviors, socioeconomic position (SEP), and psychosocial stressors on racial/ethnic obesity disparities in a multiethnic and multiracial sample of adults. Methods Using data from the Chicago Community Adult Health Study (2001-2003), Oaxaca-Blinder decomposition analysis was conducted to quantify the extent to which health behaviors (fruit and vegetable consumption and physical activity), SEP, and cumulative stressors (e.g., perceived discrimination, financial strain) each explained differences in obesity prevalence in Black, US-born Hispanic, and non-US-born Hispanic compared with non-Hispanic White participants. Results SEP and health behaviors did not explain obesity differences between racial/ethnic minorities and White individuals. Having high levels of stress in four or more domains explained 4.46% of the differences between Black and White individuals, whereas having high levels of stress in three domains significantly explained 14.13% of differences between US-born Hispanic and White. Together, the predictors explained less than 20% of differences between any racial/ethnic minority group and White individuals. Conclusions Exposure to stressors may play a role in obesity disparities, particularly among Black and US-born Hispanic individuals. Other obesity-related risk factors need to be examined to understand the underlying mechanisms explaining obesity disparities.

Objectives: The dietary patterns of Pacific Islander Americans are partially influenced by a rich cultural heritage. There is little known about how cultural affinity affects the dietary choices of this small, but quickly growing population. This analysis attempts to understand how the association of cultural affinity on island foods consumption (IFC) varies by key demographic characteristics.Design: A sample of 240 Samoan and Tongan adults in California from the Pacific Islander Health Study (PIHS) was used. Psychometric properties of a novel 11-item cultural affinity scale were assessed. Univariate and bivariate analyses of the cultural affinity scale were completed to understand the distribution of cultural affinity score. Separate multivariable Poisson regression was used to assess the effect of interactions between cultural affinity and five key demographic factors on IFC.Results: Psychometric analysis of the PIHS cultural affinity scale revealed two unique factors. Significant interactions were found between cultural affinity and ethnicity and birthplace: the association between cultural affinity and IFC was larger among Samoans compared to Tongans and Samoan or Tongan birthplace was found to have a weaker association between cultural affinity and IFC. Interactions between cultural affinity and age, financial insecurity, and educational attainment were not significant.Conclusion: Understanding how cultural affinity varies in its effect on IFC is a part of understanding overall dietary patterns in this population.

Objectives To investigate Black-White disparities in suboptimal sleep and cardiometabolic health by government-assisted rental housing status. Design National Health Interview Survey (NHIS) pooled cross-sectional data (2004–2016). Setting United States. Participants Black and White adult participants (n = 80,880). Measurements Poisson regression with robust variance was used to estimate prevalence ratios (PRs) and 95% confidence intervals for self-reported unrecommended ( 9 hours) sleep duration (each separately vs recommended (≤7–9 hours)) and sleep difficulties (eg, trouble falling/staying asleep ≥3 days/week) (yes vs no) among Blacks compared to Whites within rental housing categories (government-assisted vs unassisted), separately, for men and women. Within sex/housing categories, we applied the same approach to compare cardiometabolic health outcomes (ie, overweight/obesity, hypertension, diabetes, heart disease, stroke) between Blacks with worse sleep and Whites with recommended sleep. Models were adjusted for age and other potential confounders. Results Participants' mean age was 42 ± 18 years, 57% were female, and 30% Black. Blacks in unassisted housing had a higher prevalence of unrecommended and short sleep (PR = 1.22 [1.15–1.30] -men, PR = 1.14 [1.08–1.21] -women) compared to their White counterparts (phousing⁎race = 0.001 -men, phousing⁎race = 0.008 -women), but no Black-White differences (PR = 0.88 [0.73–1.07] -men, PR = 0.98 [0.89–1.09] -women) were observed among government-assisted renters. Generally, Blacks were less likely to report sleep difficulties than Whites. Cardiometabolic health disparities between Blacks with worse sleep and Whites with recommended sleep were generally smaller among government-assisted renters, but relationships varied by sex. Conclusions There were no racial disparities in short sleep duration, and cardiometabolic health disparities were generally attenuated when Blacks and Whites resided in government-assisted rental housing.

The purpose of this pilot, parallel, randomized controlled trial was to examine the efficacy of a self-guided online cognitive and behaviorally-based pain management intervention (Proactive Self-Management Program for Effects of Cancer Treatment [PROSPECT]) to reduce “worst” pain for individuals with chronic painful chemotherapy-induced peripheral neuropathy (CIPN). Secondary outcomes included “average” pain, nonpainful CIPN symptom severity, impression of change, and pain interference. Sixty patients with chronic painful CIPN were recruited from 5 outpatient academic and community cancer centers. Patients were randomized in a 1:1 ratio to receive either 8 weeks of PROSPECT or usual care. A 7-day electronic “worst” pain intensity diary and standardized measures of pain interference, nonpainful CIPN symptom severity, impression of change, and “average” pain were administered pre/post intervention. Postintervention mean scores were evaluated between groups using analysis of covariance adjusting for baseline. Individuals who received the PROSPECT intervention (n = 19) had significantly greater improvements in “worst pain” compared with individuals receiving usual care (n = 19; P = .046, d = .58). There were no significant differences in mean scores between groups for the secondary outcomes (n = 42). A larger, adequately powered study testing the PROSPECT intervention is needed to determine if improvements in pain may be sustained, evaluate the effect of the intervention on the secondary outcomes, and identify mediators of pain intensity-related improvement. Perspective This study explores the efficacy of an 8-week online cognitive behavioral pain management intervention for chronic painful CIPN. Intervention use resulted in greater improvements in “worst” pain than usual care alone. The findings provide preliminary support for the efficacy of a nonpharmacological intervention for chronic painful CIPN.

The 40-item University of Pennsylvania Smell Identification Test (UPSIT) is an effective instrument to detect olfactory dusfunction in Parkinson’s disease (PD). It is not clear, however, whether tests of this length are necessary to detect such dysfunction. Several studies have suggested that detection of certain odors is selectively compromised in PD, and that a test comprised of these odors could be shorter and more specific for this purpose. Therefore, we attempted to identify a subset of UPSIT odors that distinguish PD from controls with similar or improved test characteristics compared to the full test. The discriminatory power of each odor was examined using UPSIT data from a discovery cohort of 314 PD patients and 314 matched controls and ranked using multiple methods (including odds ratios, regression coefficients and discriminant analysis). To validate optimally discriminant subsets, we calculated test characteristics using data from two independent cohorts (totaling 306 PD and 343 controls). In the discovery cohort, multiple novel 12-item subsets (and the previously described Brief Smell Identification Test-B) performed similarly or improved upon the UPSIT and were better than 12 random items. However, in validation studies from independent cohorts, multiple subsets retained test characteristics similar to the full UPSIT, but did not outperform 12 random items. Differential discriminatory power of individual items is not conserved across independent cohorts arguing against selective hyposmia in PD. However, multiple 12-item subsets performed as well as the full UPSIT. These subsets could form the basis for shorter olfactory tests in the clinical evaluation of Parkinsonism., Non-motor symptoms: sniffing for a faster diagnosis A short test of olfactory function could aid the early diagnosis of Parkinson’s disease (PD). An international study led by James F. Morley at the University of Pennsylvania, USA, examined the ability of 314 PD patients and 314 matched controls to perceive 40 odors in the University of Pennsylvania Smell Identification Test (UPSIT). They used various statistical methods to determine whether tests based on a subset of these odors could distinguish PD patients from controls. Although they were not able to identify a consistent subset of smells that differentiates patients from controls, which supports the idea that there is not a PD-specific pattern of smell loss, they demonstrate that a shorter 12-item version of the UPSIT is specific and sensitive enough to detect olfactory dysfunction in PD.

Some studies document racial disparities in self-reported health associated with alcohol use and abuse. However, few studies examined biomarkers that underlie the onset of alcohol-related chronic diseases. We investigated whether the association between alcohol abuse and five biomarkers of inflammation (CRP, IL-6, fibrinogen, E-selectin, sICAM-1) vary between Black and White Americans aged 35 to 84 (n = 1173) from the Midlife in the United States Biomarker Study. Multivariable Ordinary Least Squares regressions were used to assess Black-White differences in the association between alcohol abuse and the biomarkers. Race moderated the association between alcohol abuse and CRP (b = 0.56, SE = 0.28, p = 0.048), IL-6 (b = 0.65, SE = 0.22, p = 0.004), and a composite inflammation score (b = 0.014, SE = 0.07, p = 0.041). These findings potentially shed light for why alcohol has a stronger negative association with poorer health for Blacks compared to Whites. Analysis should be replicated in larger prospective cohorts.

Objectives Health outcomes, including chronic disease and mortality, attributed to or associated with alcohol abuse are discrepant between African Americans and Whites. To date, the topic is not fully understood and few studies conducted have used biomarker indicators of health. We investigated whether the association between alcohol abuse and biomarkers of the neuroendocrine system vary between black or African American and White respondents aged 34–84 from the Midlife in the United States Study (MIDUS) II (2004–2006) ( n = 1129). Alcohol abuse was assessed with a modified version of the Michigan Alcohol Screening Test. Ordinary least squared (OLS) regression was used to evaluate whether race moderated the associations between alcohol abuse and four biomarkers—urinary cortisol and serum dehydroepiandrosterone sulfate (DHEA-S), epinephrine and norepinephrine—and two composite summary scores, each consisting of two components that characterize the hypothalamic pituitary adrenal (HPA)-axis and sympathetic nervous systems (SNS), respectively. Covariates included age, sex, education, income, current drinking, smoking, exercise, fast food consumption, heart disease, blood pressure, diabetes, body mass index, medication use, anxiety/depression, sleep duration, and cholesterol markers. Race significantly moderated the associations between alcohol abuse and norepinephrine concentration (χ 2 [1] = 4.48, p = 0.034) and the SNS composite score (χ 2 [1] = 5.83, p = 0.016). Alcohol abuse was associated with higher mean norepinephrine levels (b = 0.26, standard error (SE) = 0.12, p = 0.034) and SNS composite score (b = 0.23, SE = 0.11, p = 0.016) for African Americans compared to Whites. Interestingly, for Whites a paradoxical association between alcohol abuse, norepinephrine and SNS levels was observed; those who abused alcohol had lower mean norepinephrine levels than non-abusers. Race differences in neuroendocrine response could be biological pathways that contribute the excess risk of chronic disease and mortality attributed to alcohol abuse among African Americans compared to Whites. Replication of these analyses in larger cohorts are warranted in addition to further studies of underlying mechanisms among Blacks and Whites separately.

AIMS Psychosocial factors amplify symptoms of Interstitial Cystitis (IC/BPS). While psychosocial self-management is efficacious in other pain conditions, its impact on an IC/BPS population has rarely been studied. The objective of this review is to learn the prevalence and impact of psychosocial factors on IC/BPS, assess baseline psychosocial characteristics, and offer recommendations for assessment and treatment. METHOD Following PRISMA guidelines, primary information sources were PubMed including MEDLINE, Embase, CINAHL, and GoogleScholar. Inclusion criteria included: (i) a clearly defined cohort with IC/BPS or with Chronic Pelvic Pain Syndrome provided the IC/BPS cohort was delineated with quantitative results from the main cohort; (ii) all genders and regions; (iii) studies written in English from 1995 to April 14, 2017; (iv) quantitative report of psychosocial factors as outcome measures or at minimum as baseline characteristics. RESULTS Thirty-four of an initial 642 articles were reviewed. Quantitative analyses demonstrate the magnitude of psychosocial difficulties in IC/BPS, which are worse than average on all measures, and fall into areas of clinical concern for 7 out of 10 measures. Meta-analyses shows mean Mental Component Score of the Short-Form 12 Health Survey (MCS) of 40.80 (SD 6.25, N = 2912), where

We characterized the location and spatial distribution of whole body pain in patients with urological chronic pelvic pain syndrome using a body map. We also compared the severity of urinary symptoms, pelvic pain, nonpelvic pain and psychosocial health among patients with different pain patterns.A total of 233 women and 191 men with urological chronic pelvic pain syndrome enrolled in a multicenter, 1-year observational study completed a battery of baseline measures, including a body map describing the location of pain during the last week. Participants were categorized with pelvic pain if they reported pain in the abdomen and pelvis only. Participants who reported pain beyond the pelvis were further divided into 2 subgroups based on the number of broader body regions affected by pain, including an intermediate group with 1 or 2 additional regions outside the pelvis and a widespread pain group with 3 to 7 additional regions.Of the 424 enrolled patients 25% reported pelvic pain only and 75% reported pain beyond the pelvis, of whom 38% reported widespread pain. Participants with a greater number of pain locations had greater nonpelvic pain severity (p0.0001), sleep disturbance (p = 0.035), depression (p = 0.005), anxiety (p = 0.011), psychological stress (p = 0.005) and negative affect scores (p = 0.0004), and worse quality of life (p ≤0.021). No difference in pelvic pain and urinary symptom severity was observed according to increasing pain distribution.Three-quarters of the men and women with urological chronic pelvic pain syndrome reported pain outside the pelvis. Widespread pain was associated with greater severity of nonpelvic pain symptoms, poorer psychosocial health and worse quality of life but not with worse pelvic pain or urinary symptoms.

Introduction The phenomenon of sleep benefit (SB) in Parkinson's disease (PD), whereby waking motor function is improved despite no dopaminergic treatment overnight, is controversial. Previous studies suggested a significant discrepancy between subjective functional and objective motor improvement. The aim of this study was to determine how well subjective reporting of SB correlates with objective measures and if true motor improvement can be predicted by a standardized questionnaire. Methods Ninety-two patients with PD participated. A structured questionnaire was developed to assess subjective SB. Quantitative motor assessment was performed using a validated smartphone application. Objective motor SB was considered to be present when the waking motor function was similar or superior to the daytime on-state. Results Twenty (22%) patients showed objective motor improvement on waking compared to end-of-dose. Most patients (77%) reported subjective SB without corresponding objective motor benefit. Our structured questionnaire could not predict Motor SB. The ability to delay morning medications and a perception of indifference or paradoxical worsening following the morning levodopa dose may suggest Motor SB. Conclusions Most patients experience subjective SB with no measureable motor improvement. This perceived benefit could be related to non-motor improvement that is distinctly different to objective motor benefit.

Background Sleep benefit (SB) in Parkinson's disease refers to improved motor symptoms upon waking despite an entire night without medications. Although it was first proposed 30 years ago, this phenomenon proved difficult to investigate, and its true prevalence and underlying mechanisms remain unclear. Objective This study aimed to identify and quantify SB through measurement of motor function using a validated smartphone application and to identify disease characteristics that predicted SB. Methods Ninety-two patients recruited from 2 Movement Disorder Services were clinically assessed at home using a validated smartphone application. Each patient was tested in the on-state, at the end of dose, and on waking (before medications) 3 times. Differences between the 3 states were used to determine the impact of sleep and levodopa on motor function. SB was considered to be a “measurable improvement in parkinsonism from the end of dose.” Results The morning waking motor function of 20 patients (22%) improved compared with the end-of-dose function, with 9 patients demonstrating superior function compared with their on-state. No clinical features predicted SB. Although all participants subjectively reported motor fluctuations, only 35 patients (38%) demonstrated an objective improvement with levodopa. Patients who had SB more often demonstrated objective motor fluctuations compared with those who did not (65% vs. 31%; P = 0.008). Conclusions SB is a genuine motor phenomenon: 1 in 5 patients have a measurable improvement in motor function on waking. It remains questionable whether this improvement is a direct effect of sleep. Until its underlying mechanism is better understood, it is more appropriate to refer to this phenomenon as simply morning improvement or diurnal fluctuation of motor symptoms.

Although imaging of the living retina with adaptive optics scanning light ophthalmoscopy (AOSLO) provides microscopic access to individual cells, such as photoreceptors, retinal pigment epithelial cells, and blood cells in the retinal vasculature, other important cell classes, such as retinal ganglion cells, have proven much more challenging to image. The near transparency of inner retinal cells is advantageous for vision, as light must pass through them to reach the photoreceptors, but it has prevented them from being directly imaged in vivo. Here we show that the individual somas of neurons within the retinal ganglion cell (RGC) layer can be imaged with a modification of confocal AOSLO, in both monkeys and humans. Human images of RGC layer neurons did not match the quality of monkey images for several reasons, including safety concerns that limited the light levels permissible for human imaging. We also show that the same technique applied to the photoreceptor layer can resolve ambiguity about cone survival in age-related macular degeneration. The capability to noninvasively image RGC layer neurons in the living eye may one day allow for a better understanding of diseases, such as glaucoma, and accelerate the development of therapeutic strategies that aim to protect these cells. This method may also prove useful for imaging other structures, such as neurons in the brain.

Background and Purpose— The trajectory of neurological improvement after stroke treatment is clinically likely to be an important prognostic signal. We compared the accuracy of early longitudinal National Institutes of Health Stroke Scale (NIHSS) measurement versus other early markers of stroke severity post treatment in predicting subjects’ 90-day stroke outcome. Methods— Data are from the Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times). Stroke severity was assessed at baseline, 1, 2, 5, 30, and 90 days. Subjects’ functional outcome was assessed using the modified Rankin Scale at baseline, 30 days, and 90 days. Group-based trajectory model was used to identify distinct subgroups of longitudinal trajectories of NIHSS measured over the first 2, 5, and 30 days. The accuracy of baseline NIHSS, infarct volume, 24-hour change in NIHSS, infarct volume, and disease severity trajectory subgroups in predicting 90-day stroke outcome were assessed using logistic regression analysis. Results— Group-based trajectory model of the 2-day longitudinal NIHSS data revealed 3 distinct subgroups of NIHSS trajectories—large improvement (41.6%), minimal improvement (31.1%), and no improvement (27.3%) subgroups. Individuals in the large improvement group were more likely were more likely to exhibit good outcomes after 90 days than those in the minimal improvement or no improvement subgroup. Among candidate predictors, the 2-day trajectory subgroup variable was the most accurate in predicting 90-day modified Rankin Scale at 84.5%. Conclusions— Early trajectory of neurological improvement defined by 2-day longitudinal NIHSS data predicts functional outcomes with greater accuracy than other common variables. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01778335.