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INTRODUCTION: Early neoplastic progression of Barretts esophagus (BE) is often treated with endoscopic therapy. Although effective, some patients are refractory to therapy or recur after apparent eradication of the BE. The goal of this study was to determine whether genomic alterations within the treated BE may be associated with persistent or recurrent disease. METHODS: We performed DNA sequencing on pre-treatment esophageal samples from 45 patients who were successfully treated by endoscopic therapy and did not recur as well as pre-treatment and post-treatment samples from 40 patients who had persistent neoplasia and 21 patients who had recurrent neoplasia. The genomic alterations were compared between groups. RESULTS: The genomic landscape was similar between all groups. Patients with persistent disease were more likely to have pre-treatment alterations involving the receptor tyrosine kinase pathway ( P = 0.01), amplifications of oncogenes ( P = 0.01), and deletions of tumor suppressor genes ( P = 0.02). These associations were no longer significant after adjusting for patient age and BE length. More than half of patients with persistent (52.5%) or recurrent (57.2%) disease showed pre-treatment and post-treatment samples that shared at least 50% of their driver mutations. DISCUSSION: Pre-treatment samples were genomically similar between those who responded to endoscopic therapy and those who had persistent or recurrent disease, suggesting there is not a strong genomic component to treatment response. Although it was expected to find shared driver mutations in pre-treatment and post-treatment samples in patients with persistent disease, the finding that an equal number of patients with recurrent disease also showed this relation suggests that many recurrences represent undetected minimal residual disease.

BACKGROUND: Understanding nutritions role in multiple sclerosis (MS) can guide recommendations and intervention-based studies. OBJECTIVE: Evaluate the association between nutrition and pediatric-onset MS outcomes. METHODS: Prospective longitudinal multicenter study conducted as part of the US Network of Pediatric MS centers. Predictors were collected using a food screener estimating intake of various dietary food groups (e.g. dairy and fruits) and additional calculated indices (e.g. Healthy Eating Index (HEI)). Outcomes included time-from-enrollment to clinical relapse, new magnetic resonance imaging (MRI) T2 lesions, and Expanded Disability Status Scale (EDSS) increase. RESULTS: 353 children with MS were enrolled (mean ± SD age 15.4 ± 2.9, follow-up 3.9 ± 2.6 years). Multivariable analysis demonstrated that increased dairy by 50% of recommended intake was associated with increased relapse risk by 41% (adjusted hazard ratio (HR) 1.41, 95% CI 1.07-1.86), and risk of T2 progression by 40% (1.40, 1.12-1.74). Increased intake of fruit or vegetable above recommended, and every five-point HEI increase decreased relapse risk by 25% (0.75, 0.60-0.95), 45% (0.55, 0.32-0.96), and 15% (0.84, 0.74-0.96), respectively. No associations were found with EDSS. CONCLUSION: This work supports the influence of dietary intake on MS course, particularly with dairy intake. Future prospective study is required to establish causation.

ObjectiveDespite an increase in twin pregnancies in recent decades, the Institute of Medicine twin weight gain recommendations remain provisional and provide no guidance for the pattern or timing of weight change. We sought to characterize gestational weight change trajectory patterns and examine associations with birth outcomes in a cohort of twin pregnancies.Study designPrenatal and delivery records were examined for 320 twin pregnancies from a maternal-fetal medicine practice in Austin, TX 2011-2019. Prenatal weights for those with >1 measured weight in the first trimester and ≥3 prenatal weights were included in analyses. Trajectories were estimated to 32 weeks (mean delivery: 33.7 ± 3.3 weeks) using flexible latent class mixed models with low-rank thin-plate splines. Associations between trajectory classes and infant outcomes were analyzed using multivariable Poisson or linear regression.ResultsWeight change from prepregnancy to delivery was 15.4 ± 6.3 kg for people with an underweight body mass index, 15.4 ± 5.8 kg for healthy weight, 14.7 ± 6.9 kg for overweight, and 12.5 ± 6.4 kg for obesity. Three trajectory classes were identified: low (Class 1), moderate (Class 2), or high gain (Class 3). Class 1 (24.7%) maintained weight for 15 weeks and then gained an estimated 6.6 kg at 32 weeks. Class 2 (60.9%) exhibited steady gain with 13.5 kg predicted total gain, and Class 3 (14.4%) showed rapid gain across pregnancy with 21.3 kg predicted gain. Compared to Class 1, Class 3 was associated with higher birth weight z-score (β = 0.63, 95% confidence interval [CI]: 0.31,0.96), increased risk for large for gestational age (IRR = 5.60, 95% CI: 1.59, 19.67), and birth

WHAT IS THIS SUMMARY ABOUT?: This summary describes the results from a phase 2 study called FOENIXCCA2. The study evaluated treatment with futibatinib in people with a rare form of advanced bile duct cancer called intrahepatic cholangiocarcinoma (or iCCA), where the tumors have changes in the structure of a gene called FGFR2. These changes include FGFR2 gene fusions. Bile duct cancer often returns after surgery or cannot be treated by surgery because the tumor has spread, so it requires treatment with chemotherapy. People live for a median of 1 year after their first chemotherapy treatment and 6 months after their second treatment. This study included people whose cancer had grown/spread after one or more chemotherapy treatments. The aims of the study were to see if futibatinib could shrink the size of tumors and stop the cancer from growing/spreading and to see how long people lived when treated with futibatinib. Clinicians also looked at side effects from taking futibatinib and at how it affected peoples quality of life. WHAT WERE THE RESULTS?: Futibatinib treatment shrank tumors in over 80% of people who received treatment. Tumors shrank by at least 30% in 42% of people. Futibatinib stopped tumors from growing/spreading for a median of 9.7 months. People who took the medicine lived for a median of 21.7 months, and 72% of people were still alive after 1 year. Side effects from taking futibatinib were like those reported for similar medicines, and clinicians considered the side effects to be manageable by adjusting the dose of futibatinib or treating the side effects. Most people reported that their quality of life stayed the same or improved during the first 9 months of taking futibatinib. WHAT DO THE RESULTS MEAN?: The results support the use of futibatinib for treating people with advanced bile duct cancer. Based on the results of this study, futibatinib is now approved in the US, Europe, and Japan. Futibatinib is approved for treating adults with advanced bile duct cancer who have received previous treatment for their cancer, and whose tumors have a gene fusion or other change in the FGFR2 gene.Clinical Trial Registration: NCT02052778 (FOENIX-CCA2).

Hydroxyurea reduces sickle cell disease (SCD) complications, but medication adherence is low. We tested 2 mobile health (mHealth) interventions targeting determinants of low adherence among patients (InCharge Health) and low prescribing among providers (HU Toolbox) in a multi-center, non-randomized trial of individuals with SCD ages 15-45. We compared the percentage of days covered (PDC), labs, healthcare utilization, and self-reported pain over 24 weeks of intervention and 12 weeks post-study with a 24-week preintervention interval. We enrolled 293 patients (51% male; median age 27.5 years, 86.8% HbSS/HbSβ0-thalassemia). The mean change in PDC among 235 evaluable subjects increased (39.7% to 56.0%; P < 0.001) and sustained (39.7% to 51.4%, P < 0.001). Mean HbF increased (10.95% to 12.78%; P = 0.03). Self-reported pain frequency reduced (3.54 to 3.35 events/year; P = 0.041). InCharge Health was used ≥1 day by 199 of 235 participants (84.7% implementation; median usage: 17% study days; IQR: 4.8-45.8%). For individuals with ≥1 baseline admission for pain, admissions per 24 weeks declined from baseline through 24 weeks (1.97 to 1.48 events/patient, P = 0.0045) and weeks 25-36 (1.25 events/patient, P = 0.0015). PDC increased with app use (P < 0.001), with the greatest effect in those with private insurance (P = 0.0078), older subjects (P = 0.033), and those with lower pain interference (P = 0.0012). Of the 89 providers (49 hematologists, 36 advanced care providers, 4 unreported), only 11.2% used HU Toolbox ≥1/month on average. This use did not affect change in PDC. Tailoring mHealth solutions to address barriers to hydroxyurea adherence can potentially improve adherence and provide clinical benefits. A definitive randomized study is warranted. This trial was registered at www.clinicaltrials.gov as #NCT04080167.

PurposeEvaluate for differences in demographic and clinical characteristics, occurrence of common symptoms, symptom severity scores, and quality of life (QOL) outcomes in survivors with (n = 155) and without (n = 118) audiometrically confirmed hearing loss.MethodsSurvivors, who were recruited from throughout the San Francisco Bay area, completed the self-report questionnaires to obtain the information of demographic and clinical characteristics; the occurrence and severity of depression, anxiety, fatigue, decrements in energy, sleep disturbance, pain, and cognitive impairment; and the general and cancer-specific QOL outcomes. Parametric and non-parametric tests were used to evaluate for differences between the two survivor groups.ResultsSurvivors with audiometrically confirmed hearing loss were older, more likely to be male, were more likely to be unemployed, report a lower annual household income, and had a higher comorbidity burden. Except for the severity of worst pain, no between-group differences were found in the occurrence rates for or severity of any of the symptoms. Survivors with hearing loss reported worse physical function and general health scores.ConclusionsWhile no between-group differences in symptom occurrence rates and severity scores were found, across the total sample, a relatively high percentage of survivors who were over 6 years from their cancer diagnosis reported clinically meaningful levels of depression (25%), anxiety (50%), fatigue (40%), decrements in energy (70%), sleep disturbance (58%), cognitive impairment (57%), and pain (60%).Implications for cancer survivorsClinicians need to perform routine assessments of hearing loss, as well as common co-occurring symptoms and initiate individualized symptom management interventions.

PURPOSE: A growing body of scientific research indicates that oncology teams tend to offer individuals with cancer little clinical advice regarding medicinal cannabis (MC) and that individuals with cancer instead turn to cannabis dispensaries for MC guidance. Our objective was to investigate dispensary personnels backgrounds and trainings in MC advising. METHODS: The study design was semistructured interviews across 13 states with cannabis dispensary personnel in managerial or client-facing positions. Of 38 recruited, 26 (68%) completed interview. The primary outcome was training in MC advising. Researchers targeted thematic saturation and adhered to Consolidated Criteria for Reporting Qualitative Research. RESULTS: Of 26 participants, 54% were female, with an average age of 40 (range: 22-64) years. Half worked in client-facing roles; half worked in managerial ones. Study participants endorsed passionate commitment to their profession, often motivated by personal experience with MC therapeutics. Cannabis dispensaries often privileged sales skills over cannabis therapeutics knowledge when hiring, resulting in uneven baseline levels of cannabis therapeutics expertise among staff. Most participants reported workplace cannabis therapeutics training to be unstandardized and weak. They described dispensary personnel as resourceful in pursuing cannabis knowledge, self-financing learning in off-hours, sampling dispensary products, and exchanging knowledge. Nearly half the participants called for quality, standardized cannabis therapeutics training for dispensary personnel. CONCLUSION: The many oncology teams who defer to dispensary personnel regarding MC advising rely on a workforce who views themselves as unevenly trained. Further research should include a national survey of cannabis dispensary personnel to learn whether these findings hold true in a larger sample. If so, the oncology community must determine the best approach to clinically advising individuals with cancer about MC.

Rationale: Two distinct subphenotypes have been identified in acute respiratory distress syndrome (ARDS), but the presence of subgroups in ARDS associated with coronavirus disease (COVID-19) is unknown. Objectives: To identify clinically relevant, novel subgroups in COVID-19-related ARDS and compare them with previously described ARDS subphenotypes. Methods: Eligible participants were adults with COVID-19 and ARDS at Columbia University Irving Medical Center. Latent class analysis was used to identify subgroups with baseline clinical, respiratory, and laboratory data serving as partitioning variables. A previously developed machine learning model was used to classify patients as the hypoinflammatory and hyperinflammatory subphenotypes. Baseline characteristics and clinical outcomes were compared between subgroups. Heterogeneity of treatment effect for corticosteroid use in subgroups was tested. Measurements and Main Results: From March 2, 2020, to April 30, 2020, 483 patients with COVID-19-related ARDS met study criteria. A two-class latent class analysis model best fit the population (P = 0.0075). Class 2 (23%) had higher proinflammatory markers, troponin, creatinine, and lactate, lower bicarbonate, and lower blood pressure than class 1 (77%). Ninety-day mortality was higher in class 2 versus class 1 (75% vs. 48%; P

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG)-IgG is increasingly detected in children with CNS demyelinating diseases. Due to the clinical overlap in children with CNS demyelination with and without MOG-IgG positivity, identifying distinct characteristics would help early diagnosis. OBJECTIVE: To compare the specific features that may help differentiate MOG-IgG positive from negative children with CNS demyelinating diseases. To compare characteristics of patients with high and low MOG-IgG titers. METHODS: Children with CNS demyelinating disorders with onset before 18 years of age who were tested for MOG-IgG at the University of California San Francisco were included. This retrospective study collected the following by chart review: demographic, clinical, MRI, CSF, and treatment data. Serum was tested for MOG-IgG at Mayo Clinic by live cell-based fluorescent activated cell sorting assay with titer ≥1:20 confirming positivity. RESULTS: We assessed 65 Mog-IgG positive and 65 MOG-IgG negative patients. Median (IQR) age of onset was 7.6 (6.6) years for MOG-IgG positive and 13.8 (5.8) years for MOG-IgG negative (p

BackgroundResearch suggests that children's health and well-being are supported by core adaptive systems, including the autonomic nervous system (ANS). Despite evidence for the importance of adulthood ANS regulation in the development of disease, few studies have examined how early development may influence emerging ANS function. Therefore, we examined how infant adiposity gain during early infancy related to ANS regulation at 6 months.MethodsInfant weight and length were abstracted from birth records and measured during the 6-month assessment in a low-income, racially/ethnically diverse sample (N = 60). WHO-standardized weight-for-length-gain change was calculated across the first 6 months of life. ANS reactivity was measured as the combined sympathetic (i.e., pre-ejection period) and parasympathetic (i.e., respiratory sinus arrhythmia) nervous system responses during the developmentally challenging Still Face Paradigm (SFP). ANS "classic reactivity" response was characterized by paired sympathetic activation and parasympathetic withdrawal.ResultsLower weight-for-length gain in the first 6 months predicted classic reactivity during still face. However, greater weight-for-length gain predicted "classic reactivity" during the reunion, when infants were expected to recover, suggesting autonomic dysregulation.ConclusionsThese findings suggest an association between early life adiposity gain and the development of infant ANS regulation.ImpactAdiposity gain during early infancy was associated with autonomic nervous system regulation at 6 months. This study identifies early adiposity gain (greater than average infant weight-for-length gain) as a risk for ANS dysregulation. This research focuses on a critical developmental period of ANS plasticity. If confirmed, findings can be used to inform early intervention programs targeting obesity prevention and to promote self-regulation.

BackgroundTechnology to restore the ability to communicate in paralyzed persons who cannot speak has the potential to improve autonomy and quality of life. An approach that decodes words and sentences directly from the cerebral cortical activity of such patients may represent an advancement over existing methods for assisted communication.MethodsWe implanted a subdural, high-density, multielectrode array over the area of the sensorimotor cortex that controls speech in a person with anarthria (the loss of the ability to articulate speech) and spastic quadriparesis caused by a brain-stem stroke. Over the course of 48 sessions, we recorded 22 hours of cortical activity while the participant attempted to say individual words from a vocabulary set of 50 words. We used deep-learning algorithms to create computational models for the detection and classification of words from patterns in the recorded cortical activity. We applied these computational models, as well as a natural-language model that yielded next-word probabilities given the preceding words in a sequence, to decode full sentences as the participant attempted to say them.ResultsWe decoded sentences from the participant's cortical activity in real time at a median rate of 15.2 words per minute, with a median word error rate of 25.6%. In post hoc analyses, we detected 98% of the attempts by the participant to produce individual words, and we classified words with 47.1% accuracy using cortical signals that were stable throughout the 81-week study period.ConclusionsIn a person with anarthria and spastic quadriparesis caused by a brain-stem stroke, words and sentences were decoded directly from cortical activity during attempted speech with the use of deep-learning models and a natural-language model. (Funded by Facebook and others; ClinicalTrials.gov number, NCT03698149.).

PURPOSE: This study aimed to characterize two developmental cohorts of transgender and nonbinary youth enrolled in the Trans Youth Care Network Study and describe their gender identity-related milestones and baseline mental health and psychosocial functioning. METHODS: Trans Youth Care participants were recruited from four pediatric academic medical centers in the U.S. before initiating medical treatment for gender dysphoria either with gonadotropin-releasing hormone agonists (GnRHa) or gender-affirming hormones (GAH). GnRHa cohort data were collected from youth and a parent; GAH cohort data were collected from youth only. RESULTS: A total of 95 youth were enrolled in the GnRHa cohort. Mean age was 11.22 years (standard deviation = 1.46), and the majority were white (52.6%) and designated male at birth (51.6%). Elevated depression symptoms were endorsed by 28.6% of GnRHa cohort youth, and 22.1% endorsed clinically significant anxiety. Approximately one fourth (23.6%) endorsed lifetime suicidal ideation, with 7.9% reporting a past suicide attempt. A total of 316 youth were enrolled in the GAH cohort. The mean age was 16.0 years (standard deviation = 1.88), and the majority were white (62%) and designated female at birth (64.9%). Elevated depression symptoms were endorsed by 51.3% of the GAH cohort, and 57.3% endorsed clinically significant anxiety. Two-thirds (66.6%) endorsed lifetime suicidal ideation, with 24.6% reporting a past suicide attempt. Life satisfaction was lower among both cohorts compared with population-based norms. CONCLUSIONS: GnRHa cohort youth appear to be functioning better from a psychosocial standpoint than GAH cohort youth, pointing to possible benefits of accessing gender-affirming treatment earlier in life.

Biometric registration may improve services associated with HIV research. A cross-sectional, observational survey was used to evaluate biometric fingerprint scanning for identification (ID) verification in the setting of an HIV prevention study. Survey outcomes were dichotomized (discouraged or not discouraged) by biometric scanning and statistical analyses were used to determine if participation decreased by greater than 10% overall and after stratifying by demographic variables and risk behaviors. 206 participants were recruited from a community-based HIV and sexual health research screening program. Participants completed a quantitative survey to assess their perceptions of biometric scanning for ID verification. The majority of participants (n = 160; 77.7%) indicated no deterrence from testing due to biometric scanning, yet a significant number (n = 45; 23.3%, P

Pachydermodactyly (PDD) is a rare, benign disease associated with progressive swelling of the periarticular soft tissue of phalangeal hand joints typically treated with local steroid injections. We present a case of a 37-year-old man with PDD treated with local steroid injections. He later developed heterotopic ossification and para-articular calcifications in the injection sites. Heterotopic ossification is not associated with PDD nor is it a recognised complication of local steroid injections. This is the first case in literature of heterotopic ossification occurring after local steroid injection and brings to attention a new potential complication of a widely performed procedure.

Background & aimsNonalcoholic fatty liver disease (NAFLD) is the most common pediatric chronic liver disease. Little is known about outcomes in recognized youth.MethodsWe compared paired liver biopsies from 122 of 139 children with NAFLD (74% male; 64% white; 71% Hispanic; mean age, 13 ± 3 years; age range, 8-17 years) who received placebo and standard of care lifestyle advice in 2 double-blind, randomized clinical trials within the nonalcoholic steatohepatitis (NASH) clinical research network from 2005 through 2015. We analyzed histologic changes with respect to baseline and longitudinal change in clinical variables using regression analysis.ResultsAt enrollment, 31% of the children had definite NASH, 34% had borderline zone 1 NASH, 13% had borderline zone 3 NASH, and 21% had fatty liver but not NASH. Over a mean period of 1.6 ± 0.4 years, borderline or definite NASH resolved in 29% of the children, whereas 18% of the children with fatty liver or borderline NASH developed definite NASH. Fibrosis improved in 34% of the children but worsened in 23%. Any progression to definite NASH and/or in fibrosis was associated with adolescent age, and higher waist circumference, levels of alanine or aspartate aminotransferase, total and low-density lipoprotein cholesterol at baseline (

BackgroundGenetic variants in calsequestrin-2 (CASQ2) cause an autosomal recessive form of catecholaminergic polymorphic ventricular tachycardia (CPVT), although isolated reports have identified arrhythmic phenotypes among heterozygotes. Improved insight into the inheritance patterns, arrhythmic risks, and molecular mechanisms of CASQ2-CPVT was sought through an international multicenter collaboration.MethodsGenotype-phenotype segregation in CASQ2-CPVT families was assessed, and the impact of genotype on arrhythmic risk was evaluated using Cox regression models. Putative dominant CASQ2 missense variants and the established recessive CASQ2-p.R33Q variant were evaluated using oligomerization assays and their locations mapped to a recent CASQ2 filament structure.ResultsA total of 112 individuals, including 36 CPVT probands (24 homozygotes/compound heterozygotes and 12 heterozygotes) and 76 family members possessing at least 1 presumed pathogenic CASQ2 variant, were identified. Among CASQ2 homozygotes and compound heterozygotes, clinical penetrance was 97.1% and 26 of 34 (76.5%) individuals had experienced a potentially fatal arrhythmic event with a median age of onset of 7 years (95% CI, 6-11). Fifty-one of 66 CASQ2 heterozygous family members had undergone clinical evaluation, and 17 of 51 (33.3%) met diagnostic criteria for CPVT. Relative to CASQ2 heterozygotes, CASQ2 homozygote/compound heterozygote genotype status in probands was associated with a 3.2-fold (95% CI, 1.3-8.0; P=0.013) increased hazard of a composite of cardiac syncope, aborted cardiac arrest, and sudden cardiac death, but a 38.8-fold (95% CI, 5.6-269.1; P

BackgroundTopiramate is an effective treatment for alcohol use disorder (AUD) and has also been used in the care of mild traumatic brain injury (mTBI). This pilot study aimed to obtain a preliminary assessment of topiramate's efficacy in reducing alcohol use and post-concussive symptoms, and its potential negative impact on cognitive function in 32 Veterans with co-occurring AUD and mTBI.MethodsThis was a prospective 12-week, randomized, double-blind, placebo-controlled pilot study of flexible-dose topiramate or placebo. Primary outcome was reduction of drinking days per week within the topiramate arm. Secondary outcomes included between group comparisons of alcohol use and craving, post-concussive symptoms, and cognitive function.ResultsDrinking days per week significantly decreased within both the topiramate and placebo arm. There were no significant treatment-by-week interactions on alcohol use/craving, or post-concussive symptoms in intent-to-treat analyses. In per-protocol analyses, topiramate significantly reduced number of drinks per week compared with placebo. Topiramate transiently impaired verbal fluency and working memory. Processing speed, cognitive inhibition, and mental flexibility significantly improved between weeks 1 and 12, regardless of treatment arm.ConclusionsSignificant improvement occurred in both the topiramate and placebo groups over 12 weeks of treatment in alcohol use and post-concussive symptoms. Among treatment completers there was greater reduction of alcohol use in the topiramate arm. Topiramate was also associated with negative but transient effects on cognitive function. Results suggest both a possible benefit for topiramate treatment in reducing alcohol use and some potential for negative cognitive effects in Veterans with AUD and mTBI.

BACKGROUND: Most hookah use studies have not included racial and ethnic minorities which limits our understanding of its use among these growing populations. This study aimed to investigate the individual characteristics of hookah use patterns and associated risk behaviors among an ethnically diverse sample of college students. METHODS: A cross-sectional survey of 2460 students (aged 18-25) was conducted in 2015, and data was analyzed in 2017. Descriptive statistics were used to present the sociodemographic characteristics, hookah use-related behavior, and binge drinking and marijuana use according to the current hookah use group, including never, exclusive, dual/poly hookah use. Multivariate logistic regression was conducted to examine how hookah related behavior and other risk behaviors varied by sociodemographics and hookah use patterns. RESULTS: Among current hookah users (n = 312), 70% were exclusive hookah users and 30% were dual/poly hookah users. There were no statistically significant differences in sociodemographic characteristics except for race/ethnicity (p

Background/objectivesThe 2019 coronavirus disease (COVID-19) has been documented in a large share of nursing homes throughout the United States, leading to high rates of mortality for residents. To understand how to prevent and mitigate future outbreaks, it is imperative that we understand which nursing homes are more likely to experience COVID-19 cases. Our aim was to examine the characteristics of nursing homes with documented COVID-19 cases in the 30 states reporting the individual facilities affected.DesignWe constructed a database of nursing homes with verified COVID-19 cases as of May 11, 2020, via correspondence with and publicly available reports from state departments of health. We linked this information to nursing home characteristics and used regression analysis to examine the association between these characteristics and the likelihood of having a documented COVID-19 case.SettingAll nursing homes from 30 states that reported COVID-19 cases at the facility-level.ParticipantsNursing home residents in states reporting data.MeasurementsWhether a nursing home had a reported COVID-19 case (yes/no), and conditional on having a case, the number of cases at a nursing home.ResultsOf 9,395 nursing homes in our sample, 2,949 (31.4%) had a documented COVID-19 case. Larger facility size, urban location, greater percentage of African American residents, non-chain status, and state were significantly (P

BackgroundPatterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described.MethodsThe REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40-75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics.ResultsA total of 7770 participants were enrolled, with a median age of 50 years (interquartile range, 45-55 years); 31% were female, 43% were black or African American, 15% were Asian, 56% had a body mass index >25 (calculated as weight in kilograms divided by height in meters squared), and 49% were current or former smokers. The median CD4 T-cell count was 620/µL (interquartile range, 447-826/ µ L), and the median duration of prior ART use, 9.5 years (5.3-14.8) years. The most common ART regimens were nucleoside/nucleotide reverse-transcriptase inhibitor (NRTI) plus nonnucleoside reverse-transcriptase inhibitor (43%), NRTI plus integrase strand transfer inhibitor (25%), and NRTI plus protease inhibitor (19%). Entry ART varied by GBD region, with shifts during the trial enrollment period. In adjusted analyses, entry CD4 cell count and CD4/CD8 ratio were associated with GBD region, sex, entry regimen, duration of ART, and nadir CD4 cell count; CD4 and CD8 cell counts were also associated with body mass index and smoking status.ConclusionsThere were substantial variations in ART use by geographic region and over time, likely reflecting the local availability of specific medications, changes in treatment guidelines and provider/patient preferences. The analyses of CD4 cell counts and CD4/CD8 ratios may provide valuable insights regarding immune correlates and outcomes in people living with HIV.Clinical trials registrationNCT02344290.

BackgroundYouth involved in the juvenile justice system have high reproductive health needs and, on exiting detention, face the challenging transition of reentry. We conducted a systematic literature review to describe what is known about youths' reproductive health needs during community reentry after incarceration.MethodsWe searched PubMed, CINAHL, Cochrane Library, and Google Scholar for articles containing key words with the concepts 'child or adolescent', 'incarcerated' and 'reentry'. In the search, we defined the concept of 'reentry' as within 1 month prior to release (to include interventions involving pre-release planning) and up to 18 months after release from incarceration.ResultsOur search yielded 2187 articles. After applying all exclusion criteria, 14 articles on reproductive health remained for extraction. The articles provided data on the following aspects of youths' reproductive health: frequency of condom use (eight articles), sexual risk behaviours other than lack of condom use (seven articles), and prevalence of sexually transmitted infections (three articles).ConclusionsThe literature on the reproductive health needs of youth undergoing reentry is extremely limited. Current intervention studies yield mixed but promising results and more intervention studies that address both pre-release reentry planning and the post-incarceration period are needed. Given incarcerated youths' well-documented reproductive health disparities compared with non-incarcerated adolescents, the identified gaps represent important opportunities for future research and programmatic emphasis.

The dynamin GTPase is known to bundle actin filaments, but the underlying molecular mechanism and physiological relevance remain unclear. Our genetic analyses revealed a function of dynamin in propelling invasive membrane protrusions during myoblast fusion in vivo. Using biochemistry, total internal reflection fluorescence microscopy, electron microscopy and cryo-electron tomography, we show that dynamin bundles actin while forming a helical structure. At its full capacity, each dynamin helix captures 12-16 actin filaments on the outer rim of the helix. GTP hydrolysis by dynamin triggers disassembly of fully assembled dynamin helices, releasing free dynamin dimers/tetramers and facilitating Arp2/3-mediated branched actin polymerization. The assembly/disassembly cycles of dynamin promote continuous actin bundling to generate mechanically stiff actin super-bundles. Super-resolution and immunogold platinum replica electron microscopy revealed dynamin along actin bundles at the fusogenic synapse. These findings implicate dynamin as a unique multifilament actin-bundling protein that regulates the dynamics and mechanical strength of the actin cytoskeletal network.

We sought to understand the role of parent engagement in overcoming barriers to care for youth re-entering the community following incarceration. For this mixed methods study, we conducted quantitative surveys on healthcare needs and access with youth (n = 50) at 1-month post-incarceration, and semi-structured interviews with a subset of these youth (n = 27) and their parents (n = 34) at 1, 3, and 6-months post-incarceration (total 94 interviews). Differences by race/ethnicity and gender were assessed using Chi square test of proportions. We performed thematic analysis of interview transcripts to examine the role of parent engagement in influencing youths' access to healthcare during reentry. Most youth were from racial/ethnic minority groups and reported multiple ACEs. Girls, compared to boys, had higher ACE scores (p = 0.03), lower family connectedness (p = 0.03), and worse general health (p = 0.02). Youth-identified barriers to care were often parent-dependent and included lack of: affordable care (22%), transportation (16%), and accompaniment to health visits (14%). Two major themes emerged from the qualitative interviews: (1) parents motivate youth to seek healthcare during reentry and (2) parents facilitate the process of youth seeking healthcare during reentry. Parents are instrumental in linking youth to healthcare during reentry, dispelling prevailing myths that parents of incarcerated youth are inattentive and that youth do not want their help. Efforts that support and enhance parent engagement in access to care during reentry, such as by actively involving parents in pre-release healthcare planning, may create stronger linkages to care.

BackgroundInsight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multicenter collaboration.MethodsPatients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries. KCNE1 variants were evaluated for ECG penetrance (defined as QTc >460 ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death.ResultsA total of 32 distinct KCNE1 rare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 Type 2 Jervell and Lange-Nielsen syndrome patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9±38.6 ms) compared with genotype positive family members (441.8±30.9 ms, P

BackgroundMore smokers report using e-cigarettes to help them quit than FDA-approved pharmacotherapy.ObjectiveTo assess the association of e-cigarettes with future abstinence from cigarette and tobacco use.DesignCohort study of US sample, with annual follow-up.ParticipantsUS adult (ages 18+) daily cigarette smokers identified at Wave 1 (W1; 2013-14) of the PATH Study, who reported a quit attempt before W2 and completed W3 (n = 2443).ExposuresUse of e-cigarettes, pharmacotherapy (including nicotine replacement therapy), or no product for last quit attempt (LQA), and current daily e-cigarette use at W2.AnalysisPropensity score matching (PSM) of groups using different methods to quit.Outcome measures12+ months abstinence at W3 from cigarettes and from all tobacco (including e-cigarettes). 30+ days abstinence at W3 was a secondary outcome.ResultsAmong daily smokers with an LQA, 23.5% used e-cigarettes, 19.3% used pharmacotherapy only (including NRT) and 57.2% used no product. Cigarette abstinence for 12+ months at W3 was ~10% in each group. Half of the cigarette abstainers in the e-cigarette group were using e-cigarettes at W3. Different methods to help quitting had statistically comparable 12+ month cigarette abstinence at W3 (e-cigarettes vs no product: Risk Difference (RD) = 0.01, 95% CI: -0.04 to 0.06; e-cigarettes vs pharmacotherapy: RD = 0.02, 95% CI:-0.04 to 0.09). Likewise, daily e-cigarette users at W2 did not show a cessation benefit over comparable no-e-cigarette users and this finding was robust to sensitivity analyses. Abstinence for 30+ days at W3 was also similar across products.LimitationsThe frequency of e-cigarette use during the LQA was not assessed, nor was it possible to assess continuous abstinence from the LQA.ConclusionAmong US daily smokers who quit cigarettes in 2014-15, use of e-cigarettes in that attempt compared to approved cessation aids or no products showed similar abstinence rates 1-2 years later.

PurposeWe aimed to described 25-hydroxyvitamin D [25(OH)D] levels in newly diagnosed colorectal cancer (CRC) patients and to re-evaluate levels after chemotherapy.MethodsPermanent residents of the San Francisco Bay Area with a new CRC diagnosis of any stage were recruited prior to any non-surgical therapy. Serum 25(OH)D levels were measured at time of diagnosis and 6-month follow-up. Supplement use was not restricted. The primary endpoint was the frequency of vitamin D deficiency in patients with newly diagnosed CRC of all stages. The Kruskal-Wallis and Spearman correlation tests were used to evaluate associations of patient characteristics with 25(OH)D levels.ResultsMedian 25(OH)D level at baseline was 27.0 ng/mL (range 7.2, 59.0); 65% of patients had insufficient levels (25(OH)D

PurposeWhile older adults with cancer are more likely to develop chemotherapy-induced peripheral neuropathy (CIPN), the study aimed to determine if patient-reported and objective measures of CIPN differ by age among cancer survivors.MethodsCancer survivors with persistent CIPN after completion of platinum and/or taxane chemotherapy completed CIPN questionnaires (severity, interference with activities, sensory, and motor symptoms) and objective testing (light touch, vibration, pain, cold sensation). CIPN measures were compared by age group (

ContextRecent, albeit, limited evidence suggests that body mass index (BMI) may be a modifiable risk factor to reduce the deleterious effects of chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors.ObjectivesTo evaluate for differences in demographic, clinical, pain, sensation, and balance characteristics among three BMI groups. We hypothesized that as BMI increased, survivors would report higher pain intensity scores and have significant decrements in measures of sensation and balance.MethodsA total of 416 survivors with CIPN were evaluated using subjective and objective measures of CIPN. Survivors were divided into three BMI groups (i.e., normal weight, overweight, and obese). Differences among the BMI groups were evaluated using parametric and nonparametric statistics.ResultsOf the 416 survivors, 45.4% were normal weight, 32.5% were overweight, and 22.1% were obese. Compared with the normal-weight group, survivors in the other two groups had lower functional status scores, a higher comorbidity burden, higher pain intensity scores, and higher interference scores. In addition, compared with the normal-weight group, survivors in the other two BMI groups had significantly worse balance scores.ConclusionOur findings support the hypothesis that as BMI increased, pain sensation and balance characteristics worsened. Our findings suggest that nutritional counseling as well as exercise and weight management programs in survivors with CIPN may improve these clinically important problems.

Objectives: This article describes the implementation of a group medical visit (GMV) model to increase access to integrative oncology (IO) care. The most challenging and critical time to access high-quality IO care is while patients are receiving conventional cancer therapy. Often demand for individual IO clinic consultations precludes this from occurring. A three-session GMV program was designed to alleviate barriers to receiving integrative care during active cancer treatment. Design: A consolidated framework was used for implementation research and focused ethnography methods to describe the IO GMV implementation process. Data sources included patient evaluations, participant observation, and brief provider and patient interviews. Setting: A pilot program was created to assess the feasibility and acceptability of implementing IO GMVs at a comprehensive cancer center. Intervention: Each three-session GMV consisted of a didactic session, followed by individual visits with the integrative oncologist. Results: The setting, intervention, and implementation process of the IO GMV program were described. Thirty-two patients participated in the first five cohorts of the program. Twenty-two were women; 24 were White. The median age of participants was 52. Patient evaluations demonstrate high levels of satisfaction with the program with all scored aspects rated >4.0 on a five-point Likert scale. For the medical center, group visits are a financially viable alternative to individual IO visits; revenue from group visits exceeded the revenue potential of 6 h of individual visits by an average of 38%. Conclusion: GMVs are a feasible and promising model for increasing access to IO. Patients in active cancer treatment were able to participate in the program. Future research and implementation efforts could examine health outcomes over time after participation in GMVs, as well as the feasibility of using this model with more diverse patient populations.

Study objectiveBecause of the high reproductive health risks that commercially sexually exploited youth (CSEY) face, we sought to understand facilitators and barriers related to their use of condoms and hormonal contraception. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We conducted semistructured interviews with 21 female CSEY. Interviews were audio-recorded, transcribed, and coded for emergent themes. Participants were enrolled through group homes and a juvenile specialty court serving CSEY.ResultsOverall, CSEY reported relatively easy access to hormonal contraception and condoms, expressing a strong preference for condoms as their primary form of contraception. Most respondents described an aversion toward hormonal birth control, attributed to personal experiences and peer accounts of side effects. Many also shared a common belief that hormonal methods are "unnatural," cause infertility, and have low efficacy. Although youth expressed a preference for condom use, they also reported frequent unprotected sex. Furthermore, there were notable barriers to hormonal contraception and condom use that were specific to youths' sexual exploitation, primarily because of their lack of control while trafficked.ConclusionAlthough participants noted relatively easy access to contraception, a number of barriers to condom and hormonal contraceptive use exist. Many of these barriers align with youth identified in other at-risk adolescent populations, however, CSEY also face a number of barriers that might be attributable to their unique experience of commercial sexual exploitation. Contraceptive education that dispels prevailing myths, sets clear expectations regarding side effects, and emphasizes autonomy is most likely to resonate with their world view and experiences.

ObjectiveWe sought to quantify the association between child incarceration in the United States and subsequent adult health outcomes.MethodsWe analyzed National Longitudinal Study of Adolescent to Adult Health data from 1727 adult (Wave IV) participants first incarcerated at age

UNLABELLED: Engaging with vocal sounds is critical for childrens social-emotional learning, and children with autism spectrum disorder (ASD) often tune out voices in their environment. Little is known regarding the neurobiological basis of voice processing and its link to social impairments in ASD. Here, we perform the first comprehensive brain network analysis of voice processing in children with ASD. We examined neural responses elicited by unfamiliar voices and mothers voice, a biologically salient voice for social learning, and identified a striking relationship between social communication abilities in children with ASD and activation in key structures of reward and salience processing regions. Functional connectivity between voice-selective and reward regions during voice processing predicted social communication in children with ASD and distinguished them from typically developing children. Results support the Social Motivation Theory of ASD by showing reward system deficits associated with the processing of a critical social stimulus, mothers voice, in children with ASD. EDITORIAL NOTE: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editors assessment is that minor issues remain unresolved (see decision letter).

The role of tobacco marketing in tobacco use, particularly among the vulnerable ethnic and socioeconomic sub-populations is a regulatory priority of the U.S. Food and Drug Administration. There currently exist both ethnic and socioeconomic disparities in the use of tobacco products. Monitoring such inequalities in exposure to tobacco marketing is essential to inform tobacco regulatory policy that may reduce known tobacco-related health disparities. We use data from the Population Assessment of Tobacco and Health (PATH) Wave 1 youth survey to examine (1) recalled exposure to and liking of tobacco marketing for cigarettes, non-large cigars, and e-cigarettes, (2) self-reported exposure to specific tobacco marketing tactics, namely coupons, sweepstakes, and free samples, and (3) self-reported impact of tobacco marketing and promotions on product use. Findings indicate that African Americans and those of lower SES were more likely to recall having seen cigarette and non-large cigar ads. Reported exposure to coupons, sweepstakes and free samples also varied ethnically and socioeconomically. African Americans and those of lower SES were more likely than other respondents to report that marketing and promotions as played a role in their tobacco product use. Better understanding of communication inequalities and their influence on product use is needed to inform tobacco regulatory action that may reduce tobacco company efforts to target vulnerable groups. Tobacco education communication campaigns focusing on disproportionately affected groups could help counter the effects of targeted industry marketing.

ObjectivesNonalcoholic fatty liver disease (NAFLD) is common; however, no information is available on how pediatric gastroenterologists in the United States manage NAFLD. Therefore, study objectives were to understand how pediatric gastroenterologists in the US approach the management of NAFLD, and to identify barriers to care for children with NAFLD.MethodsWe performed structured one-on-one interviews to ascertain each individual pediatric gastroenterologist's approach to the management of NAFLD in children. Responses were recorded from open-ended questions regarding screening for comorbidities, recommendations regarding nutrition, physical activity, medications, and perceived barriers to care.ResultsResponse rate was 72.0% (486/675). Mean number of patients examined per week was 3 (standard deviation [SD] 3.5). Dietary intervention was recommended by 98.4% of pediatric gastroenterologists. Notably, 18 different dietary recommendations were reported. A majority of physicians provided targets for exercise frequency (72.6%, mean 5.6 days/wk, SD 1.6) and duration (69.9%, mean 40.2 minutes/session, SD 16.4). Medications were prescribed by 50.6%. Almost one-half of physicians (47.5%) screened for type 2 diabetes, dyslipidemia, and hypertension. Providers who spent more than 25 minutes at the initial visit were more likely to screen for comorbidities (P = 0.003). Barriers to care were reported by 92.8% with 29.0% reporting ≥3 barriers.ConclusionsThe majority of US pediatric gastroenterologists regularly encounter children with NAFLD. Varied recommendations regarding diet and exercise highlight the need for prospective clinical trials. NAFLD requires a multidimensional approach with adequate resources in the home, community, and clinical setting.

ObjectivesNumbness associated with neuropathic pain suggests the loss of function in myelinated, large diameter sensory neurons. The purpose of this study was to examine the relationships between pain severity and subjective (ie, severity of numbness) and objective (ie, loss of light touch sensations, vibration thresholds) measures of loss of large fiber function in adult survivors with chemotherapy-induced peripheral neuropathy (CIPN, n=426) and breast cancer patients with persistent postsurgical pain (n=80).Material and methodsFor both samples, average pain and numbness were evaluated using a 0 to 10 numeric rating scale. Loss of light touch sensations in the hands and feet of patients with CIPN and in the upper arm of patients at 5 and 6 months following breast cancer surgery were assessed using Semmes Weinstein monofilaments. Loss of vibration in the hands and feet of patients with CIPN was assessed using a biothesiometer. Pearson Product Moment correlation coefficients were calculated between average pain and the number or percentage of sites with loss of light touch sensations, mean vibration thresholds, and the severity of numbness.ResultsFor both pain conditions, average pain scores were significantly correlated with objective measures of large fiber function (r=0.12 to 0.34; all P

BackgroundInitiation of antiretroviral therapy (ART) following diagnosis of HIV infection at birth is an emerging area of paediatric HIV care. We present outcomes of HIV-infected infants identified at birth at Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa.MethodsFrom September, 2013 (era 1), only high-risk HIV-exposed infants were offered diagnostic HIV PCR tests at birth. From June, 2014 (era 2), all HIV-exposed infants were offered laboratory-based diagnostic PCR tests. From October, 2014 (era 3), point of care (POC) diagnostic PCR tests were also done if staff availability allowed. We describe time to ART initiation, mortality, retention in care, and viral suppression among the HIV-infected infants identified across these eras.FindingsWe tested 5449 HIV-exposed infants who were born between Sept 1, 2013, and June 30, 2016. 88 neonates with confirmed HIV infection were identified and included in the study, of which 86 (98%) started ART. Median age at ART initiation decreased from 9 days (IQR 6-25) in eras 1 and 2 to 2 days (1-8) in era 3. In era 3, more neonates who were co-tested with POC testing started ART within 48 h of birth (29 [83%] of 35; median 1 day [IQR 1-2]) than infants who were not co-tested (one [4%] of 29; median 6 days [5-10]). The probability of mortality by 12 months across the eras was 14% (95% CI 8-24) and did not differ by era. Of the 72 infants who survived and initiated ART at the site, 56 (78%) were retained at 12 months. Of the 56 infants retained in care, 40 (71%) had a viral load less than 400 copies per mL at 12 months, with no differences between eras (p=0·23).InterpretationHIV-infected infants can be identified at birth and ART can be initiated within hours to days. Although most infants in our cohort started ART, mortality remained unacceptably high with suboptimal retention and viral suppression. Reducing mortality and improving retention and viral suppression remain urgent priorities.FundingEunice Kennedy Shriver National Institute of Child Health and Human Development/National Institute of Allergy and Infectious Disease, National Institutes of Health, USAID/PEPfAR, and the South African National HIV Programme.

Deficits in executive control functions are some of the most common and disabling consequences of both military and civilian brain injury. However, effective interventions are scant. The goal of this study was to assess whether cognitive rehabilitation training that was successfully applied in chronic civilian brain injury would be effective for military veterans with traumatic brain injury (TBI). In a prior study, participants with chronic acquired brain injury significantly improved after training in Goal-Oriented Attentional Self-Regulation (GOALS) on measures of attention/executive function, functional task performance, and goal-directed control over neural processing on functional magnetic resonance imaging. The objective of this study was to assess effects of GOALS training in veterans with chronic TBI. A total of 33 veterans with chronic TBI and executive difficulties in their daily life completed either 5 weeks of manualized GOALS training or Brain-Health Education (BHE) matched by time and intensity. Evaluator-blinded assessments at baseline and post-training included neuropsychological and complex functional task performance and self-report measures of emotional regulation. After GOALS, but not BHE training, participants significantly improved from baseline on primary outcome measures of Overall Complex Attention/Executive Function composite neuropsychological performance score (F = 7.10, p = 0.01; partial η2 = 0.19), and on overall complex functional task performance (Goal Processing Scale Overall Performance; F = 6.92, p = 0.01, partial η2 = 0.20). Additionally, post-GOALS participants indicated significant improvement on emotional regulation self-report measures (Profile of Mood States Confusion Score; F = 6.05, p = 0.02, partialη2 = 0.20). Training in attentional self-regulation applied to participant-defined goals may improve cognitive functioning in veterans with chronic TBI. Attention regulation training may not only impact executive control functioning in real-world complex tasks, but also may improve emotional regulation and functioning. Implications for treatment of veterans with TBI are discussed.

ContextAlthough paclitaxel is one of the most commonly used drugs to treat breast, ovarian, and lung cancers, little is known about the impact of paclitaxel-induced peripheral neuropathy (PIPN) on cancer survivors.ObjectivesThe purposes of this study were to evaluate for differences in demographic and clinical characteristics as well as measures of sensation, balance, upper extremity function, perceived stress, symptom burden, and quality of life (QOL) between survivors who received paclitaxel and did (n = 153) and did not (n = 58) develop PIPN.MethodsPain characteristics associated with PIPN are described in detail. Both subjective and objective measures were used to evaluate the impact of PIPN.ResultsSurvivors with PIPN were significantly older, had a higher body mass index, and a worse comorbidity profile. The duration of PIPN was almost four years, and pain scores were in the moderate range. Compared with survivors without PIPN, survivors with PIPN had a higher number of upper and lower extremity sites that had lost light touch, cold, and pain sensations. Survivors with PIPN had worse upper extremity function, more problems with balance, a higher symptom burden, and higher levels of perceived stress. In addition, survivors with PIPN had worse QOL scores particularly in the domain of physical functioning.ConclusionThe findings from this large descriptive study are the first to document the impact of PIPN on survivors' symptom burden, functional status, and QOL.

More than half of adult tobacco users in the United States (U.S.) transitioned in tobacco product use between 2013⁻2014 and 2014⁻2015. We examine how characteristics of adult tobacco users in the U.S. relate to transitions in tobacco product use. Population Assessment of Tobacco and Health (PATH) Study data were analyzed from 12,862 adult current tobacco users who participated in Wave 1 (W1, 2013⁻2014) and Wave 2 (W2, 2014⁻2015). Three types of transitions were examined-(1) adding tobacco product(s); (2) switching to non-cigarette tobacco product(s); and (3) discontinuing all tobacco use-among those currently using: (1) any tobacco product; (2) cigarettes only (i.e., exclusive cigarette); and (3) cigarettes plus another tobacco product(s) (i.e., poly-cigarette). Multinomial logistic regression analyses determined relative risk of type of transition versus no transition as a function of demographic and tobacco use characteristics. Transitions in tobacco product use among adult tobacco users were common overall, but varied among different demographic groups, including by age, sex, sexual orientation, race/ethnicity, educational attainment, and poverty level. Further, cigarette smokers with higher dependence scores were more likely to add product(s) and less likely to discontinue tobacco use compared to those with low dependence scores. That high nicotine dependence is a barrier to discontinuing tobacco use adds evidence to support policy to lower nicotine content of cigarettes and to evaluate new products for their potential to reduce cigarette use.

More than half of adult tobacco users in the United States (U.S.) transitioned in tobacco product use between 2013⁻2014 and 2014⁻2015. We examine how characteristics of adult tobacco users in the U.S. relate to transitions in tobacco product use. Population Assessment of Tobacco and Health (PATH) Study data were analyzed from 12,862 adult current tobacco users who participated in Wave 1 (W1, 2013⁻2014) and Wave 2 (W2, 2014⁻2015). Three types of transitions were examined-(1) adding tobacco product(s); (2) switching to non-cigarette tobacco product(s); and (3) discontinuing all tobacco use-among those currently using: (1) any tobacco product; (2) cigarettes only (i.e., exclusive cigarette); and (3) cigarettes plus another tobacco product(s) (i.e., poly-cigarette). Multinomial logistic regression analyses determined relative risk of type of transition versus no transition as a function of demographic and tobacco use characteristics. Transitions in tobacco product use among adult tobacco users were common overall, but varied among different demographic groups, including by age, sex, sexual orientation, race/ethnicity, educational attainment, and poverty level. Further, cigarette smokers with higher dependence scores were more likely to add product(s) and less likely to discontinue tobacco use compared to those with low dependence scores. That high nicotine dependence is a barrier to discontinuing tobacco use adds evidence to support policy to lower nicotine content of cigarettes and to evaluate new products for their potential to reduce cigarette use.

ContextThe most common adverse effects from neurotoxic chemotherapy are chemotherapy-induced neuropathy (CIPN), hearing loss, and tinnitus. Although associations between perceived stress and persistent pain, hearing loss, and tinnitus are documented, no studies have examined these associations in cancer survivors who received neurotoxic chemotherapy.ObjectivesIn this cross-sectional study, we evaluated for associations between perceived stress and the occurrence of CIPN, hearing loss, and tinnitus, in 623 adult cancer survivors who received platinum and/or taxane compounds.MethodsSurvivors completed self-report measures of hearing loss, tinnitus, and perceived stress (i.e., Impact of Events Scale-Revised [IES-R]). Separate logistic regression analyses were done for each neurotoxicity to evaluate whether each of the IES-R subscale (i.e., intrusion, avoidance, hyperarousal) and total scores made a significant independent contribution to neurotoxicity group membership.ResultsOf the 623 survivors in this study, 68.4% had CIPN, 34.5% reported hearing loss, and 31.0% reported tinnitus. Older age, higher body mass index, poorer functional status, being born prematurely, cancer diagnosis, and higher intrusion (P = 0.013), hyperarousal (P = 0.014), and total (P = 0.047) IES-R scores were associated with CIPN. Older age, being male, poorer functional status, a worse comorbidity profile, and a higher IES-R hyperarousal (P = 0.007) score were associated with hearing loss. Being male, having less education, a worse comorbidity profile, and a higher IES-R hyperarousal (P = 0.029) score were associated with tinnitus.ConclusionThese findings suggest that increased levels of perceived stress are associated with the most common chemotherapy-induced neurotoxicities.

ObjectiveTo determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines.Study designThis multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention.ResultsThere were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications.ConclusionsMore than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management.

PurposeLimited information is available on the impact of chemotherapy (CTX)-induced neurotoxicity on adult survivors' symptom experience and quality of life (QOL). Purposes were to describe occurrence of hearing loss and tinnitus and evaluate for differences in phenotypic characteristics and measures of sensation, balance, perceived stress, symptom burden, and QOL between survivors who received neurotoxic CTX and did (i.e., neurotoxicity group) and did not (i.e., no neurotoxicity group) develop neurotoxicity. Neurotoxicity was defined as the presence of chemotherapy-induced neuropathy (CIN), hearing loss, and tinnitus. Survivors in the no neurotoxicity group had none of these conditions.MethodsSurvivors (n = 609) completed questionnaires that evaluated hearing loss, tinnitus, stress, symptoms, and QOL. Objective measures of sensation and balance were evaluated.ResultsOf the 609 survivors evaluated, 68.6% did and 31.4% did not have CIN. Of the survivors without CIN, 42.4% reported either hearing loss and/or tinnitus and 48.1% of the survivors with CIN reported some form of ototoxicity. Compared to the no neurotoxicity group (n = 110), survivors in the neurotoxicity group (n = 85) were older, were less likely to be employed, had a higher comorbidity burden, and a higher symptom burden, higher levels of perceived stress, and poorer QOL (all p

Purpose Although incarceration may have life-long negative health effects, little is known about associations between child incarceration and subsequent adult health outcomes. The paper aims to discuss this issue. Design/methodology/approach The authors analyzed data from 14,689 adult participants in the National Longitudinal Study of Adolescent to Adult Health (Add Health) to compare adult health outcomes among those first incarcerated between 7 and 13 years of age (child incarceration); first incarcerated at>or=14 years of age; and never incarcerated. Findings Compared to the other two groups, those with a history of child incarceration were disproportionately black or Hispanic, male, and from lower socio-economic strata. Additionally, individuals incarcerated as children had worse adult health outcomes, including general health, functional limitations (climbing stairs), depressive symptoms, and suicidality, than those first incarcerated at older ages or never incarcerated. Research limitations/implications Despite the limitations of the secondary database analysis, these findings suggest that incarcerated children are an especially medically vulnerable population. Practical implications Programs and policies that address these medically vulnerable children's health needs through comprehensive health and social services in place of, during, and/or after incarceration are needed. Social implications Meeting these unmet health and social service needs offers an important opportunity to achieve necessary health care and justice reform for children. Originality/value No prior studies have examined the longitudinal relationship between child incarceration and adult health outcomes.

Background & aimsFocal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD.MethodsWe performed a cross-sectional study of baseline data from 813 children (age

PurposeThe purpose of this study was to evaluate for differences in demographic, clinical, and pain characteristics, as well as measures of sensation, balance, perceived stress, symptom burden, and quality of life (QOL) among survivors who received neurotoxic chemotherapy (CTX) and who reported only chemotherapy-induced neuropathy (CIN, n = 217), CIN and hearing loss (CIN/HL, n = 69), or CIN, hearing loss, and tinnitus (CIN/HL/TIN, n = 85). We hypothesized that as the number of neurotoxicities increased, survivors would have worse outcomes.MethodsSurvivors were recruited from throughout the San Francisco Bay area. Survivors completed self-report questionnaires for pain and other symptoms, stress and QOL. Objective measures were assessed at an in person visit.ResultsCompared to survivors with only CIN, survivors with all three neurotoxicities were less likely to be female and less likely to report child care responsibilities. In addition, survivors with all three neurtoxicities had higher worst pain scores, greater loss of protective sensation, and worse timed get up and go scores. These survivors reported higher state anxiety and depression and poorer QOL. For some outcomes (e.g., longer duration of CIN, self-reported balance problems), significantly worse outcomes were found for the survivors with CIN/HL and CIN/HL/TIN compared to those with only CIN.ConclusionsOur findings suggest that compared to survivors with only CIN, survivors with CIN/HL/TIN are at increased risk for the most severe symptom burden, significant problems associated with sensory loss and changes in balance, as well as significant decrements in all aspects of QOL.

BackgroundFew patients recover full hand dexterity after an acquired brain injury such as stroke. Repetitive somatosensory electrical stimulation (SES) is a promising method to promote recovery of hand function. However, studies using SES have largely focused on gross motor function; it remains unclear if it can modulate distal hand functions such as finger individuation.ObjectiveThe specific goal of this study was to monitor the effects of SES on individuation as well as on cortical oscillations measured using EEG, with the additional goal of identifying neurophysiological biomarkers.MethodsEight participants with a history of acquired brain injury and distal upper limb motor impairments received a single two-hour session of SES using transcutaneous electrical nerve stimulation. Pre- and post-intervention assessments consisted of the Action Research Arm Test (ARAT), finger fractionation, pinch force, and the modified Ashworth scale (MAS), along with resting-state EEG monitoring.ResultsSES was associated with significant improvements in ARAT, MAS and finger fractionation. Moreover, SES was associated with a decrease in low frequency (0.9-4 Hz delta) ipsilesional parietomotor EEG power. Interestingly, changes in ipsilesional motor theta (4.8-7.9 Hz) and alpha (8.8-11.7 Hz) power were significantly correlated with finger fractionation improvements when using a multivariate model.ConclusionsWe show the positive effects of SES on finger individuation and identify cortical oscillations that may be important electrophysiological biomarkers of individual responsiveness to SES. These biomarkers can be potential targets when customizing SES parameters to individuals with hand dexterity deficits.Trial registrationNCT03176550; retrospectively registered.

Magnetic resonance elastography (MRE) is a promising technique for noninvasive assessment of fibrosis, a major determinant of outcome in nonalcoholic fatty liver disease (NAFLD). However, data in children are limited. The purpose of this study was to determine the accuracy of MRE for the detection of fibrosis and advanced fibrosis in children with NAFLD and to assess agreement between manual and novel automated reading methods. We performed a prospective, multicenter study of two-dimensional (2D) MRE in children with NAFLD. MR elastograms were analyzed manually at two reading centers, and using a new automated technique. Analysis using each approach was done independently. Correlations were determined between MRE analysis methods and fibrosis stage. Thresholds for classifying the presence of fibrosis and of advanced fibrosis were computed and cross-validated. In 90 children with a mean age of 13.1 ± 2.4 years, median hepatic stiffness was 2.35 kPa. Stiffness values derived by each reading center were strongly correlated with each other (r = 0.83). All three analyses were significantly correlated with fibrosis stage (center 1, ρ = 0.53; center 2, ρ = 0.55; and automated analysis, ρ = 0.52; P

IntroductionThis study investigated associations between maternal prepregnancy BMI and child behaviors at ages 9-11 years and examine interaction by race and gender.MethodsThe National Longitudinal Survey of Youth and the Children and Young Adults surveys are U.S.-based, ongoing longitudinal studies, initiated in 1979 and 1986, respectively. Mothers (n=2,952) reported pregnancy and child (n=5,660) developmental information at multiple time points. Child total, internalizing, and externalizing problems at ages 9-11 years were assessed using the Behavior Problems Index (BPI), collected biennially until 2012. Associations between prepregnancy BMI and child BPI outcomes were examined, as well as two- and three-way interactions by race and gender. Analyses were conducted in 2017.ResultsBoys whose mothers had higher prepregnancy weights exhibited higher total BPI and externalizing scores at ages 9-11 years versus those with normal-weight mothers. Boys with severely obese mothers had higher total BPI (mean difference=7.99, 95% CI=3.53, 12.46) and externalizing (mean difference=5.77, 95% CI=1.50, 10.04) scores. Prepregnancy underweight was associated with boys' higher total BPI (mean difference=2.34, 95% CI=0.02, 4.66) and externalizing (mean difference=3.30, 95% CI=0.69, 5.91); these associations were not significant in sensitivity analyses. No associations emerged for girls or internalizing problems. Two-way interactions by race and three-way interactions by race and gender were not significant.ConclusionsMaternal prepregnancy weight was associated with BPI level among boys. Boys with severely obese mothers exhibited markedly higher behavioral problems at ages 9-11 years versus those with normal-weight mothers, regardless of race. Maintaining healthy prepregnancy weight may be important for preventing boys' deleterious behavior outcomes in middle childhood.