Exploring individual fixel-based white matter abnormalities in epilepsy.

Diffusion MRI has provided insight into the widespread structural connectivity changes that characterize epilepsies. Although syndrome-specific white matter abnormalities have been demonstrated, studies to date have predominantly relied on statistical comparisons between patient and control groups. For diffusion MRI techniques to be of clinical value, they should be able to detect white matter microstructural changes in individual patients. In this study, we apply an individualized approach to a technique known as fixel-based analysis, to examine fibre-tract-specific abnormalities in individuals with epilepsy. We explore the potential clinical value of this individualized fixel-based approach in epilepsy patients with differing syndromic diagnoses. Diffusion MRI data from 90 neurologically healthy control participants and 10 patients with epilepsy (temporal lobe epilepsy, progressive myoclonus epilepsy, and Dravet Syndrome, malformations of cortical development) were included in this study. Measures of fibre density and cross-section were extracted for all participants across brain white matter fixels, and mean values were computed within select tracts-of-interest. Scanner harmonized and normalized data were then used to compute Z-scores for individual patients with epilepsy. White matter abnormalities were observed in distinct patterns in individual patients with epilepsy, both at the tract and fixel level. For patients with specific epilepsy syndromes, the detected white matter abnormalities were in line with expected syndrome-specific clinical phenotypes. In patients with lesional epilepsies (e.g. hippocampal sclerosis, periventricular nodular heterotopia, and bottom-of-sulcus dysplasia), white matter abnormalities were spatially concordant with lesion location. This proof-of-principle study demonstrates the clinical potential of translating advanced diffusion MRI methodology to individual-patient-level use in epilepsy. This technique could be useful both in aiding diagnosis of specific epilepsy syndromes, and in localizing structural abnormalities, and is readily amenable to other neurological disorders. We have included code and data for this study so that individualized white matter changes can be explored robustly in larger cohorts in future work.

White matter abnormalities characterize the acute stage of sports-related mild traumatic brain injury.

Sports-related concussion, a form of mild traumatic brain injury, is characterized by transient disturbances of brain function. There is increasing evidence that functional brain changes may be driven by subtle abnormalities in white matter microstructure, and diffusion MRI has been instrumental in demonstrating these white matter abnormalities in vivo. However, the reported location and direction of the observed white matter changes in mild traumatic brain injury are variable, likely attributable to the inherent limitations of the white matter models used. This cross-sectional study applies an advanced and robust technique known as fixel-based analysis to investigate fibre tract-specific abnormalities in professional Australian Football League players with a recent mild traumatic brain injury. We used the fixel-based analysis framework to identify common abnormalities found in specific fibre tracts in participants with an acute injury (≤12 days after injury; n = 14). We then assessed whether similar changes exist in subacute injury (>12 days and <3 months after injury; n = 15). The control group was 29 neurologically healthy control participants. We assessed microstructural differences in fibre density and fibre bundle morphology and performed whole-brain fixel-based analysis to compare groups. Subsequent tract-of-interest analyses were performed within five selected white matter tracts to investigate the relationship between the observed tract-specific abnormalities and days since injury and the relationship between these tract-specific changes with cognitive abnormalities. Our whole-brain analyses revealed significant increases in fibre density and bundle cross-section in the acute mild traumatic brain injury group when compared with controls. The acute mild traumatic brain injury group showed even more extensive differences when compared with the subacute injury group than with controls. The fibre structures affected in acute concussion included the corpus callosum, left prefrontal and left parahippocampal white matter. The fibre density and cross-sectional increases were independent of time since injury in the acute injury group, and were not associated with cognitive deficits. Overall, this study demonstrates that acute mild traumatic brain injury is characterized by specific white matter abnormalities, which are compatible with tract-specific cytotoxic oedema. These potential oedematous changes were absent in our subacute mild traumatic brain injury participants, suggesting that they may normalize within 12 days after injury, although subtle abnormalities may persist in the subacute stage. Future longitudinal studies are needed to elucidate individualized recovery after brain injury.

Motivational interviewing telephone counseling to increase postpartum maintenance of abstinence from tobacco.

Although many women quit smoking while pregnant, rates of relapse after delivery are high. We examined the effectiveness of motivational interviewing (MI) in maintaining postpartum abstinence from smoking among pregnant women who recently quit smoking (N = 382), randomized to receive five brief MI phone counseling calls or to a prenatal and postpartum care as usual control condition. Relapse to smoking was assessed at 3, 6, and 12 months postpartum based on self-report and urine cotinine. Cox regressions compared conditions on relapse outcomes and hazard ratio of total number of MI calls was examined to probe dose-response effects. Results revealed no difference in the hazard ratio of relapse between treatment condition and no dose-response effect of total number of MI calls. Phone counseling in the prenatal and postpartum period did not facilitate maintenance of abstinence among new mothers. Considerations for future intervention development studies on relapse prevention during the postpartum period are discussed.

Incidence and Secondary Transmission of SARS-CoV-2 Infections in Schools.

BACKGROUND: In an effort to mitigate the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), North Carolina closed prekindergarten through grade 12 public schools to in-person instruction on March 14, 2020. On July 15, 2020, North Carolina's governor announced schools could open via remote learning or a hybrid model that combined in-person and remote instruction. In August 2020, 56 of 115 North Carolina school districts joined The ABC Science Collaborative (ABCs) to implement public health measures to prevent SARS-CoV-2 transmission and share lessons learned. We describe secondary transmission of SARS-CoV-2 within participating school districts during the first 9 weeks of in-person instruction in the 2020-2021 academic year. METHODS: From August 15, 2020 to October 23, 2020, 11 of 56 school districts participating in ABCs were open for in-person instruction for all 9 weeks of the first quarter and agreed to track incidence and secondary transmission of SARS-CoV-2. Local health department staff adjudicated secondary transmission. Superintendents met weekly with ABCs faculty to share lessons learned and develop prevention methods. RESULTS: Over 9 weeks, 11 participating school districts had >90 000 students and staff attend school in person. Among these students and staff, 773 community-acquired SARS-CoV-2 infections were documented by molecular testing. Through contact tracing, health department staff determined an additional 32 infections were acquired within schools. No instances of child-to-adult transmission of SARS-CoV-2 were reported within schools. CONCLUSIONS: In the first 9 weeks of in-person instruction in North Carolina schools, we found extremely limited within-school secondary transmission of SARS-CoV-2, as determined by contact tracing.

Cognitive Behavioral Therapy for Antenatal Depression in a Pilot Randomized Controlled Trial and Effects on Neurobiological, Behavioral and Cognitive Outcomes in Offspring 3-7 Years Postpartum: A Perspective Article on Study Findings, Limitations and Future Aims.

PURPOSE OF ARTICLE: In a previous pilot randomized controlled trial including 54 pregnant women with depression, maternal mood improved after Cognitive Behavioural Therapy (CBT) compared to treatment as usual (TAU), showing medium to large effect sizes. The effect persisted up to 9 months postpartum, with infant outcomes also showing medium to large effects favoring CBT in various child domains. This perspective article summarizes the results of a follow-up that was performed approximately 5 years later in the same cohort, assessing the effects of antenatal Cognitive Behavioural Therapy for depression and anxiety on child buccal cell DNA-methylation, brain morphology, behavior and cognition. FINDINGS: Children from the CBT group had overall lower DNA-methylation compared to children from the TAU group. Mean DNA-methylation of all NR3C1 promoter-associated probes did not differ significantly between the CBT and TAU groups. Children from the CBT group had a thicker right lateral occipital cortex and lingual gyrus. In the CBT group, Voxel-Based-Morphometry analysis identified one cluster showing increased gray matter concentration in the right medial temporal lobe, and fixel-based analysis revealed reduced fiber-bundle-cross-section in the Fornix, the Optical Tract, and the Stria Terminalis. No differences were observed in full-scale IQ or Total Problems Score. When the total of hypotheses tests in this study was considered, differences in DNA-methylation and brain measurements were no longer significant. SUMMARY: Our explorative findings suggest that antenatal depression treatment decreases overall child DNA-methylation, increases cortical thickness, and decreases white matter fiber-bundle cross-section in regions involved in cognitive function and the stress response. Nevertheless, larger studies are warranted to confirm our preliminary conclusion that CBT in pregnancy alters neurobiological outcomes in children. Clinical relevance remains unclear as we found no effects of antenatal CBT on child behavior or cognition (yet).

Brain Magnetic Resonance Imaging Findings in Children after Antenatal Maternal Depression Treatment, a Longitudinal Study Built on a Pilot Randomized Controlled Trial.

Antenatal depression is associated with an increased risk of offspring neuro-developmental disorders, potentially as a consequence of an altered brain development in utero. We hypothesized that reducing maternal depression by Cognitive Behavioral Therapy (CBT) during pregnancy may ameliorate the offspring's brain (micro)structural outcomes. 54 pregnant women with a diagnosed clinical depression were randomly allocated to CBT or Treatment as Usual (TAU), showing moderate to large depression symptom improvements after CBT. In 16 of their children (69% boys, N(TAU) = 8, N(CBT) = 8, mean age = 5.9 years, range = 3.9-7.1 years) brain Magnetic Resonance Imaging (MRI) scans were conducted. Children from the CBT group had a thicker right lateral occipital cortex (difference: 0.13 mm, 95% CI = 0.005-0.26) and lingual gyrus (difference: 0.18 mm, 95% CI = 0.01-0.34). In the CBT group, Voxel-Based Morphometry analysis identified one cluster showing increased gray matter concentration in the right medial temporal lobe at p < 0.05 uncorrected, and fixel-based analysis revealed reduced fiber-bundle cross-section in the Fornix, the Optical Tract, and the Stria Terminalis at p < 0.01 uncorrected. However, none of the results survived correction for multiple testing. Our explorative analyses provided some indication that antenatal CBT for depression may ameliorate offspring's brain (micro)structural outcomes, but the sample size was extremely small, and our results should be cautiously interpreted. Larger studies are warranted to confirm our preliminary conclusions that CBT for antenatal depression affects brain development in children.

Relation of Pregnancy Loss to Risk of Cardiovascular Disease in Parous Postmenopausal Women (From the Women's Health Initiative).

Women with history of pregnancy loss (PL) have higher burden of cardiovascular disease (CVD) later in life, yet it is unclear whether this is attributable to an association with established CVD risk factors (RFs). We examined whether PL is associated with CVD RFs and biomarkers in parous postmenopausal women in the Women's Health Initiative, and whether the association between PL and CVD RFs accounted for the association between PL and incident CVD. Linear and logistic regressions were used to estimate associations between baseline history of PL and CVD RFs. Cox proportional hazards regression models were used to estimate the associations between baseline history of PL and incident CVD after adjustment for baseline RFs. Of 79,121 women, 27,272 (35%) had experienced PL. History of PL was associated with higher body mass index (p < 0.0001), hypertension (p < 0.0001), diabetes (p = 0.003), depression (p < 0.0001), and lower income (p < 0.0001), physical activity (p = 0.01), poorer diet (p < 0.0001), smoking (p < 0.0001), and alcohol use (p < 0.0001). After adjustment for CVD RFs, PL was significantly associated with incident CVD over mean follow up of 16 years (hazard ratio 1.11, 95% confidence interval 1.06 to 1.16). In conclusion, several CVD RFs are associated with PL, but they do not entirely account for the association between PL and incident CVD.

An Electronic Interview Tracking Tool to Guide Medical Students Through the Match: Improvements in Advising and Match Outcomes.

PROBLEM: Medical students are applying to increasing numbers of residency programs to increase their likelihood of success in the Match. However, they have limited data to help them understand their level of competitiveness or identify programs to which they should apply. APPROACH: In 2014-2015 (Match year 2015), the University of Maryland School of Medicine's (UMSOM's) Office of Student Affairs (OSA) implemented an electronic interview tracking tool in which students update their residency application interview status on an ongoing basis. OSA deans can filter and sort data by student, specialty, program, academic metrics, and interview status. The deans use these data to advise students in real time, provide students with examples of programs to consider, and engage clinical faculty to support students at risk of not matching. OUTCOMES: In the Match years 2015, 2016, and 2017, respectively, 86% (n = 135/157), 87% (n = 138/159), and 94% (n = 151/161) of UMSOM students participated actively in this tracking tool, adding over 3,000 data points per year. Following the tool's launch, the average number of applications per student remained stable. The UMSOM's Match rate and percentages of students self-reporting a match in their top three choices and rating the school's advising as "very useful" all increased, without comparable increases in national data. NEXT STEPS: This tool, which provides students with data-driven examples of programs to which they should consider applying, may be beneficial to students, faculty, and program directors at other institutions-and to the residency application process, if adopted broadly.

What matters in patient-centered medical home transformation: Whole system evaluation outcomes of the Brown Primary Care Transformation Initiative.

OBJECTIVES: Patient-centered medical home transformation initiatives for enhancing team-based, patient-centered primary care are widespread in the United States. However, there remain large gaps in our understanding of these efforts. This article reports findings from a contextual, whole system evaluation study of a transformation intervention at eight primary care teaching practice sites in Rhode Island. It provides a picture of system changes from the perspective of providers, staff, and patients in these practices. METHODS: Quantitative/qualitative evaluation methods include patient, provider, and staff surveys and qualitative interviews; practice observations; and focus groups with the intervention facilitation team. RESULTS: Patient satisfaction in the practices was high. Patients could describe observable elements of patient-centered medical home functioning, but they lacked explicit awareness of the patient-centered medical home model, and their activation decreased over time. Providers' and staff's emotional exhaustion and depersonalization increased slightly over the course of the intervention from baseline to follow-up, and personal accomplishment decreased slightly. Providers and staff expressed appreciation for the patient-centered medical home as an ideal model, variously implemented some important patient-centered medical home components, increased their understanding of patient-centered medical home as more than specific isolated parts, and recognized their evolving work roles in the medical home. However, frustration with implementation barriers and the added work burden they associated with patient-centered medical home persisted. CONCLUSION: Patient-centered medical home transformation is disruptive to practices, requiring enduring commitment of leadership and personnel at every level, yet the model continues to hold out promise for improved delivery of patient-centered primary care.

Self-Reported Environmental Tobacco Smoke Exposure and Avoidance Compared with Cotinine Confirmed Tobacco Smoke Exposure among Pregnant Women and Their Infants.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) presents substantial health risks for pregnant women and newborn infants. Measurements of ETS include invasive and expensive biochemical tests, as well as less invasive and lower-cost, self-reported exposure and avoidance measures. Better understanding of self-report measures will help to select ETS assessments for evaluation. METHODS: This analysis was conducted within the context of a tailored video intervention to reduce tobacco smoking and ETS exposure during pregnancy and after delivery in the control group sample of 147 nonsmoking women. Measurements of salivary cotinine concentration, self-reported ETS exposure, and avoidance behaviors were captured at 32 weeks’ gestation and 6 months postpartum. RESULTS: Salivary cotinine concentration was significantly related to ETS avoidance among pregnant nonsmokers at 32 weeks’ gestation, but not ETS exposure. At 6 months postpartum, both the reported ETS exposure of the infant and maternal avoidance behaviors to reduce her infant’s exposure were associated with the infant’s salivary cotinine concentration. At 32 weeks’ gestation and 6 months postpartum, avoidance behaviors decreased as exposure increased. DISCUSSION: This study suggests that for nonsmoking women during pregnancy, reports of tobacco smoke avoidance are more valid than reports of exposure. After delivery, self-reported ETS exposure or avoidance are associated with each other and the biochemical measurement of salivary cotinine. These results provide researchers and clinicians with evidence to support the inclusion of avoidance behaviors in the selection of ETS measures.

Comparing the Validity of Self-Report and Urinalysis for Substance Use among Former Inmates in the Northeastern United States.

BACKGROUND: Problems with self-reported drug use include difficulties with recall and recognition as well as the desire to respond to questions in a socially desirable manner. Various methods have been developed to improve and/or validate estimates based on direct questioning of individuals regarding their substance use. For this study, we were interested in validating self-reported use of: 1) tobacco, 2) marijuana, and 3) other substances (i.e., heroin, cocaine, opiates, oxycodone, benzodiazepines, methamphetamine, phencyclidine, and barbiturates) employing urinalysis among inmates who participated in a randomized controlled trial of a smoking abstinence intervention in a tobacco-free prison located in the northeastern United States. METHODS: Two-hundred and seven men and women with a mean age of 34.9 (standard deviation = 9.0) completed questions regarding their substance use on a 7-day Timeline Follow-Back and provided urine specimens three weeks following prison release. RESULTS: Self-reported tobacco and marijuana use were highly consistent with urine drug testing in terms of overall agreement and Kappa (93.7% and.804 for tobacco, respectively; and 90.3% and.804 for marijuana, respectively); however, consistency was much lower for other drug use grouped together (62.7% and.270). DISCUSSION: Although some former inmates may not accurately report substance use, our findings indicate that they are in the minority, suggesting that self-report is valid for tobacco and marijuana use but much less so for other drugs grouped together. Future research should be conducted with a larger and more diverse sample of former inmates to establish the generalizability of our findings from this study.

Inhaled Treprostinil Drug Delivery During Mechanical Ventilation and Spontaneous Breathing Using Two Different Nebulizers.

OBJECTIVES: To determine the feasibility of delivering inhaled treprostinil during mechanical ventilation and spontaneous unassisted ventilation using the Tyvaso Inhalation System and the vibrating mesh nebulizer. We sought to compare differences in fine particle fraction, and absolute inhaled treprostinil mass delivered to neonatal, pediatric, and adult models affixed with a face mask, conventional, and high-frequency ventilation between Tyvaso Inhalation System and with different nebulizer locations between Tyvaso Inhalation System and vibrating mesh nebulizer. DESIGN: Fine particle fraction was first determined via impaction with both the Tyvaso Inhalation System and vibrating mesh nebulizer. Next, a test lung configured with neonatal, pediatric, and adult mechanics and a filter to capture medication was attached to a realistic face model during spontaneous breathing or an endotracheal tube during conventional ventilation and high-frequency oscillator ventilator. Inhaled treprostinil was then nebulized with both the Tyvaso Inhalation System and vibrating mesh nebulizer, and the filter was analyzed via high-performance liquid chromatography. Testing was done in triplicate. Independent two-sample t tests were used to compare mean fine particle fraction and inhaled mass between devices. Analysis of variance with Tukey post hoc tests were used to compare within device differences. SETTING: Academic children's hospital aerosol research laboratory. MEASUREMENTS AND MAIN RESULTS: Fine particle fraction was not different between the Tyvaso Inhalation System and vibrating mesh nebulizer (0.78 ± 0.04 vs 0.77 ± 0.08, respectively; p = 0.79). The vibrating mesh nebulizer delivered the same or greater inhaled treprostinil than the Tyvaso Inhalation System in every simulated model and condition. When using the vibrating mesh nebulizer, delivery was highest when using high-frequency oscillator ventilator in the neonatal and pediatric models, and with the nebulizer in the distal position in the adult model. CONCLUSIONS: The vibrating mesh nebulizer is a suitable alternative to the Tyvaso Inhalation System for inhaled treprostinil delivery. Fine particle fraction is similar between devices, and vibrating mesh nebulizer delivery meets or exceeds delivery of the Tyvaso Inhalation System. Delivery for infants and children during high-frequency oscillator ventilator with the vibrating mesh nebulizer may result in higher than expected dosages.

A tailored video intervention to reduce smoking and environmental tobacco exposure during and after pregnancy: Rationale, design and methods of Baby's Breath.

Low-cost interventions to decrease environmental tobacco smoke (ETS) exposure of pregnant women and their newborns are needed to lower health risks of exposed fetuses and infants. Baby's Breath is a tailored video intervention developed and tested in a randomized controlled trial. The study aimed to test the efficacy of tailored video versus usual care approaches to reduce the ETS exposure of fetuses of low-income women during and after pregnancy; and to assess this intervention separately among non-smoking and smoking women. Participating women, recruited early in pregnancy, who spoke English, were at least 18years old, smoke exposed (current smokers, quit smoking on their own, or were exposed to smoke of others), pregnant with only one baby, and had access to a telephone and video player, were randomized to experimental or control conditions. Intervention participants received newsletters containing content aimed at smoking cessation and avoidance (5 during and 3 after pregnancy), in addition to videos (3 during and 2 after pregnancy) individually tailored on behavioral theory-based survey questions. Comparison participants received newsletters and videos on healthy pregnancy topics. Outcomes included salivary cotinine of both mother and baby (32weeks gestation and 6months postpartum) as well as self-reported ETS exposure and avoidance behaviors. This study may demonstrate the efficacy of a low-cost intervention to decrease ETS exposure, and will fill an important gap in describing the utility of this innovative intervention technology, as well as demonstration of potential benefits to this type of intervention.

Reproductive history and risk of type 2 diabetes mellitus in postmenopausal women: findings from the Women's Health Initiative.

OBJECTIVE: The aim of the study was to understand the association between women's reproductive history and their risk of developing type 2 diabetes. We hypothesized that characteristics signifying lower cumulative endogenous estrogen exposure would be associated with increased risk. METHODS: Prospective cohort analysis of 124,379 postmenopausal women aged 50 to 79 years from the Women's Health Initiative (WHI). We determined age of menarche and final menstrual period, and history of irregular menses from questionnaires at baseline, and calculated reproductive length from age of menarche and final menstrual period. Presence of new onset type 2 diabetes was from self-report. Using multivariable Cox proportional hazards models, we assessed associations between reproductive variables and incidence of type 2 diabetes. RESULTS: In age-adjusted models, women with the shortest (<30 y) reproductive periods had a 37% (95% CI, 30-45) greater risk of developing type 2 diabetes than women with medium-length reproductive periods (36-40 y). Women with the longest (45+ y) reproductive periods had a 23% (95% CI, 12-37) higher risk than women with medium-length periods. These associations were attenuated after full adjustment (HR 1.07 [1.01, 1.14] for shortest and HR 1.09 [0.99, 1.22] for longest, compared with medium duration). Those with a final menstrual period before age 45 and after age 55 had an increased risk of diabetes (HR 1.04; 95% CI, 0.99-1.09 and HR 1.08; 95% CI, 1.01-1.14, respectively) compared to those with age of final menstrual period between 46 and 55 years. Timing of menarche and cycle regularity was not associated with risk after full adjustment. CONCLUSIONS: Reproductive history may be associated with type 2 diabetes risk. Women with shorter and longer reproductive periods may benefit from lifestyle counseling to prevent type 2 diabetes.