Hypoxia inducible factors regulate infectious SARS-CoV-2, epithelial damage and respiratory symptoms in a hamster COVID-19 model.

Understanding the host pathways that define susceptibility to Severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) infection and disease are essential for the design of new therapies. Oxygen levels in the microenvironment define the transcriptional landscape, however the influence of hypoxia on virus replication and disease in animal models is not well understood. In this study, we identify a role for the hypoxic inducible factor (HIF) signalling axis to inhibit SARS-CoV-2 infection, epithelial damage and respiratory symptoms in the Syrian hamster model. Pharmacological activation of HIF with the prolyl-hydroxylase inhibitor FG-4592 significantly reduced infectious virus in the upper and lower respiratory tract. Nasal and lung epithelia showed a reduction in SARS-CoV-2 RNA and nucleocapsid expression in treated animals. Transcriptomic and pathological analysis showed reduced epithelial damage and increased expression of ciliated cells. Our study provides new insights on the intrinsic antiviral properties of the HIF signalling pathway in SARS-CoV-2 replication that may be applicable to other respiratory pathogens and identifies new therapeutic opportunities.

Voluntary, temporary out-of-home firearm storage: A survey of firearm retailers and ranges in two states.

Out-of-home storage of personal firearms is one recommended option for individuals at risk of suicide, and statewide online maps of storage locations have been created in multiple states, including Colorado and Washington. We sought to examine both the extent to which firearm retailers and ranges offer temporary, voluntary firearm storage and the perceived barriers to providing this service. We invited all firearm retailers and ranges in Colorado and Washington to complete an online or mailed survey; eligible sites had to have a physical location where they could provide storage. Between June-July 2021, 137 retailers/ranges completed the survey (response rate = 25.1%). Nearly half (44.5%) of responding firearm retailers/ranges in Colorado and Washington State indicated they had ever provided firearm storage. Among those who had ever offered storage, 80.3% currently offered storage while 19.7% no longer did. The majority (68.6%) of participants had not heard of the Colorado/Washington gun storage maps and 82.5% did not believe they were currently listed on the maps. Respondents indicated liability waivers would most influence their decision about whether to start or continue providing temporary, voluntary storage of firearms. Understanding current practices, barriers, and concerns about providing out-of-home storage by retailers and ranges may support development of more feasible approaches for out-of-home firearm storage during times of suicide risk.

Progesterone Increases Nicotine Withdrawal and Anxiety in Male but Not Female Smokers During Brief Abstinence.

INTRODUCTION: Although exogenous progesterone may hold promise as a treatment for nicotine use disorders, it is unclear whether it is similarly effective in males and females. This study examined the effects of progesterone on nicotine use disorder comprehensively using behavioral, psychological, and neural measures in male and female smokers exposed to brief abstinence. AIMS AND METHODS: Thirty-three male and 33 female non-treatment-seeking smokers participated in a double-blind, randomized, placebo-controlled crossover study of 200 mg of progesterone or placebo daily over a four-day abstinence period. Smoking behavior and subjective effects of nicotine were assessed at baseline and after final drug administration. Nicotine withdrawal, smoking urges, mood states, and neural response to smoking cues were measured at baseline, after the first drug administration, and after the final drug administration. RESULTS: No main effect of drug (progesterone vs. placebo) emerged for any outcome. Significant sex by drug interactions emerged for nicotine withdrawal (p = .020), perceived strength of nicotine (p = .040), and perceived bad effects of nicotine (p = .029). Males receiving progesterone reported worse nicotine withdrawal (p = .046) and a trend towards decreased bad effects of nicotine (p = .070). Males on progesterone also reported greater tension and anxiety relative to placebo (p = .021). Females on progesterone perceived nicotine's effects as being stronger relative to placebo (p = .046). CONCLUSIONS: Progesterone causes sex-dependent effects on smoking-related outcomes during brief abstinence. Specifically, progesterone in males may increase rather than decrease nicotine withdrawal and negative affect during abstinence, potentially hindering efforts to quit smoking. IMPLICATIONS: In male and female smokers undergoing a brief period of abstinence, we examined the effects of progesterone on smoking outcomes. While progesterone had limited effects in female smokers, in males, it worsened nicotine withdrawal and negative affect. Our findings emphasize the importance of analyzing sex differences in future studies examining progesterone as a potential treatment and suggest that progesterone in males could potentially exacerbate aspects of nicotine dependence. CLINICALTRIALS.GOV REGISTRATION: NCT01954966. https://clinicaltrials.gov/ct2/show/NCT01954966.

Course of Illness and Treatment Updates for Bipolar Disorder in the Perinatal Period.

PURPOSE OF REVIEW: The perinatal period is a time of increased vulnerability for people with bipolar disorder (BD). The purpose of this review is to provide an update of the literature from the last 3 years regarding course of illness and treatments for BD in the perinatal period to guide clinical care. RECENT FINDINGS: Postpartum manic and depressive episodes are emerging as having a unique presentation that may differentiate them from non-perinatal mood episodes. Many important updates regarding medication treatment in the perinatal period have been published recently that have considered the risks of untreated illness versus treatment risks in this population.' Despite significant research, there are still gaps in knowledge regarding safety and efficacy of medications for the mother and child. Crucial future areas of study include improved screening guidelines, randomized controlled trials examining medication safety in pregnancy and lactation, and efficacy of nonpharmacologic treatments.

Application of gap time analysis with flexible hazards to pulmonary exacerbations in the EPIC observational study.

Cystic fibrosis and other chronic lung disease clinical trials often use time to first pulmonary exacerbation (PEx) or total PEx count as endpoints. The use of these outcomes may fail to capture patterns or timing of multiple exacerbations and how covariates influence the risk of future exacerbations. Analysis of gap times between PEx provides a useful framework to understand risks of subsequent events, particularly to assess if there is a temporary increase in a hazard of a subsequent PEx following the occurrence of a PEx. This may be useful for estimating the amount of time needed to follow patients after a PEx and predicting which patients are more likely to have multiple PEx. We propose a smoothed hazard for gap times to account for elevated hazards after exacerbations. A simulation study was conducted to explore model performance and was able to appropriately estimate parameters in all situations with an underlying change point with independent or correlated recurrent events. Models with different change-point structures and trends are compared using Early Pseudomonas Infection Control (EPIC) observational study data, using a quasi-likelihood modification of the Akaike information criterion; a model with a change-point provided a better fit than a model without one. The analysis suggests that the change point may be 1.8 years (SE 0.09) after the end of a PEx. Models including covariates in the hazard function revealed that having one or two copies of the Δ$\Delta$ F508 mutation, female sex, and higher numbers of previous PEx were significantly associated with increased risk of another PEx.

Structure-Guided Engineering of a Family IV Cold-Adapted Esterase Expands Its Substrate Range.

Cold active esterases have gained great interest in several industries. The recently determined structure of a family IV cold active esterase (EstN7) from Bacillus cohnii strain N1 was used to expand its substrate range and to probe its commercially valuable substrates. Database mining suggested that triacetin was a potential commercially valuable substrate for EstN7, which was subsequently proved experimentally with the final product being a single isomeric product, 1,2-glyceryl diacetate. Enzyme kinetics revealed that EstN7's activity is restricted to C2 and C4 substrates due to a plug at the end of the acyl binding pocket that blocks access to a buried water-filled cavity. Residues M187, N211 and W206 were identified as key plug forming residues. N211A stabilised EstN7 allowing incorporation of the destabilising M187A mutation. The M187A-N211A double mutant had the broadest substrate range, capable of hydrolysing a C8 substrate. W206A did not appear to have any significant effect on substrate range either alone or when combined with the double mutant. Thus, the enzyme kinetics and engineering together with a recently determined structure of EstN7 provide new insights into substrate specificity and the role of acyl binding pocket plug residues in determining family IV esterase stability and substrate range.

Discontinuation of hormonal contraception due to changes in mood and decreases in sexual desire: the role of adverse childhood experiences.

PURPOSE: To evaluate if adverse childhood experiences are associated with hormonal contraception discontinuation due to mood and sexual side effects. MATERIALS AND METHODS: Women, ages 18-40 (N = 826), with current and/or previous hormonal contraceptive use completed surveys on demographics, contraceptive history, and the Adverse Childhood Experiences Questionnaire. We characterised women into high (≥2 adverse experiences) and low (0 or 1) adverse childhood experience groups. We calculated risk ratios for associations between adverse childhood experiences and outcomes of interest using log binomial generalised linear models, and adjusted for relevant demographic variables. RESULTS: Women in the high adverse childhood experiences group (n = 355) were more likely to report having discontinued hormonal contraception due to decreases in sexual desire (adjusted risk ratio 1.44, 1.03-2.00, p = .030). Covariates included age, current hormonal contraception use, and various demographic variables associated with discontinuation. Adverse childhood experiences were not associated with mood or sexual side effects among current (n = 541) hormonal contraceptive users. CONCLUSIONS: Self-reported adverse childhood experiences were associated with greater likelihood of discontinuing hormonal contraception due to behavioural side effects, particularly decreases in sexual desire. Identification of risk factors for behavioural side effects can assist patients and clinicians in making informed choices on contraception that minimise risk of early discontinuation.

Pathways Through Which Health Literacy Is Linked to Parental Oral Health Behavior in an American Indian Tribe.

BACKGROUND: Health literacy (HL) is the "ability to find, understand, evaluate and put information to use to improve decision making and, ultimately, improve health and quality of life." Parents with limited HL are less likely to follow recommended parental oral health behaviors. PURPOSE: We tested a theoretical framework designed to clarify mechanisms through which HL may influence parental oral health behavior. The framework proposed that HL: (a) has a direct effect on parental oral health knowledge, beliefs (i.e. self-efficacy; perceived susceptibility, severity, benefits, barriers), and behavior; (b) influences beliefs indirectly through knowledge; and (c) influences behavior indirectly through knowledge and beliefs. METHODS: We analyzed cross-sectional data from a randomized controlled trial designed to reduce dental decay in American Indian children (N = 521). Parents completed survey questions assessing sociodemographic characteristics, HL, and parental oral health knowledge, beliefs, and behavior. Path analysis was used to test the framework. RESULTS: HL exerted significant direct effects on knowledge and beliefs but not behavior. HL had significant indirect effects on all beliefs through knowledge. Significant indirect effects of HL on behavior occurred through self-efficacy (estimate: 0.99, 95% CI: 0.42, 1.83, p = .005), perceived barriers (estimate: 0.73, 95% CI: 0.29, 1.43, p = .010), knowledge to self-efficacy (estimate: 0.57, 95% CI: .31, 0.98, p = .001), and knowledge to perceived barriers (estimate: 0.24, 95% CI: 0.09, 0.47, p = .012). CONCLUSIONS: HL exerted an indirect effect on parental oral health behavior, with knowledge, self-efficacy, and perceived barriers being the primary constructs linking HL to behavior.

Birth outcomes are superior after transfer of fresh versus frozen embryos for donor oocyte recipients.

STUDY QUESTION: For donor oocyte recipients, are birth outcomes superior for fresh versus frozen embryos? SUMMARY ANSWER: Among fresh donor oocyte recipients, fresh embryos are associated with better birth outcomes when compared with frozen embryos. WHAT IS KNOWN ALREADY: Frozen embryo transfer (ET) with vitrification has been associated with improved pregnancy rates, but also increased rates of large for gestational age infants. Donor oocyte recipients represent an attractive biological model to attempt to isolate the impact of embryo cryopreservation on IVF outcomes, yet there is a paucity of studies in this population. STUDY DESIGN, SIZE, DURATION: A retrospective cohort of the US national registry, the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, of IVF cycles of women using fresh donor oocytes resulting in ET between 2013 and 2015. Thawed oocytes were excluded. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Good obstetric outcome (GBO), defined as a singleton, term, live birth with appropriate for gestational age birth weight, was the primary outcome measure. Secondary outcomes included live birth, clinical pregnancy, spontaneous abortion, preterm birth, multiple births and gestational age-adjusted weight. Outcomes were modeled using the generalized estimating equation approach. MAIN RESULTS AND THE ROLE OF CHANCE: Data are from 25 387 donor oocyte cycles, in which 14 289 were fresh and 11 098 were frozen ETs. A GBO was 27% more likely in fresh ETs (26.3%) compared to frozen (20.9%) (adjusted risk ratio 1.27; 95% confidence interval (CI) 1.21-1.35; P < 0.001). Overall, fresh transfer was more likely to result in a live birth (55.7% versus 39.5%; adjusted risk ratio 1.21; 95% CI 1.18-1.26; P < 0.001). Among singleton births, there was no difference in gestational age-adjusted birth weight between groups. LIMITATION, REASONS FOR CAUTION: Our cohort findings contrast with data from autologous oocytes. Prospective studies with this population are warranted. WIDER IMPLICATIONS OF THE FINDINGS: Among donor oocyte recipients, fresh ETs may be associated with better birth outcomes. Reassuringly, given its prevalent use, modern embryo cryopreservation does not appear to result in phenotypically larger infants. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Enduring impact of childhood adversity on lower urinary tract symptoms in adult women.

AIMS: To determine whether childhood adversity is associated with self-reported lower urinary tract symptoms (LUTS) among older adult women. METHODS: A convenience sample of women (≥55 years old) who presented to an academic urology practice or who had participated in a previous bladder health prevention study completed questionnaires including the LUTS Tool (on frequency and bother of LUTS), the Adverse Childhood Experiences (ACEs) Questionnaire, the Spielberger State-Trait Anxiety Inventory, and the Center for Epidemiologic Studies Depression Scale. RESULTS: The average age (SD) of participants (N = 151) was 64.7 (6.9) years. The total number of ACEs predicted the total number of LUTS, ß = .39 (95% confidence interval [CI] = 0.14, 0.64), P = .003, as well as LUTS frequency, ß = .09 (95% CI = 0.04, 0.13), P < .001. ACEs predicted bother for nocturia, ß = 0.12 (95% CI = 0.03, 0.22), P = .008. Negative affect symptoms did not mediate the relationship between the total number of ACEs and the total number of LUTS. Rather, ACEs predicted LUTS and negative affect symptoms through (at least partially) independent pathways. Analyses controlled for tobacco use, number of vaginal deliveries, hypertension, overactive bladder medication use, body mass index, income, and race because these variables were significantly associated with the total number of ACEs or total number of LUTS. CONCLUSIONS: Childhood adversity has an enduring impact on risk for LUTS in adulthood even when controlling for potential confounds and this relationship cannot be explained by negative affect symptoms.

Development of Betta splendens embryos and larvae reveals variation in pigmentation patterns.

Vertebrate pigmentation provides an ideal system for studying the intersections between evolution, genetics, and developmental biology. Teleost fish, with their accessible developmental stages and intense and diverse colours produced by chromatophores, are an ideal group for study. We set out to test whether Betta splendens is a good model organism for studying the evolution and development of diverse pigmentation. Our results demonstrate that B. splendens can be bred to produce large numbers of offspring with easily visualized pigment cells. Depending on the colour of the parents, there was variation in larval pigmentation patterns both within and between breeding events. In juveniles the developing adult pigmentation patterns showed even greater variation. These results suggest that B. splendens has great potential as a model organism for pigmentation studies.

Depressed, stressed, and inflamed: C-reactive protein linked with depression symptoms in midlife women with both childhood and current life stress.

To determine whether the relationship between inflammatory factors and clinically significant depression symptoms is moderated by high exposure to adverse childhood experiences and current life stressors in a longitudinal community cohort of midlife women. Methods: Participants from the Penn Ovarian Ageing Study community cohort (age at baseline: M = 45.3 [SD = 3.8]) were included in analyses if they had a blood sample measuring basal inflammatory markers during at least one visit where depression symptom severity and current stressful life events were also assessed (N = 142, average number of visits per participant = 1.75 [SD = 0.92]). Approximately annually over the course of 16 years, participants self-reported depression symptom severity using the Centre for Epidemiologic Studies Depression (CESD) Scale, provided menstrual diaries to determine menopause stage, and contributed blood samples. Residual blood samples were assayed for interleukin (IL)-6, IL 1-beta (IL-1ß), tumour necrosis factor alpha (TNF-α), and high sensitivity C-reactive protein (hsCRP). Early life stress was quantified using the Adverse Childhood Experiences questionnaire (low [0-1 experience(s)] versus high [≥ 2 experiences]). Current stressful life events were assessed using a structured interview (low [0-1 events] vs. high [≥ 2 events]). Generalised estimating equation models were used to model associations with the outcome of interest-clinically significant depression symptoms (CESD ≥16)-and risk factors: inflammatory marker levels (log transformed), adverse childhood experiences group, and current life stressors group. Covariates included menopause stage, age at study baseline, body mass index, race, and smoking status. We found a significant three-way interaction between log hsCRP levels, adverse childhood experiences group, and current life stressors group on likelihood of experiencing clinically significant depression symptoms (OR: 4.33; 95% CI: 1.22, 15.46; p = 0.024) after adjusting for covariates. Solely for women with high adverse childhood experiences and with high current life stressors, higher hsCRP was associated with higher odds of having clinically significant depression symptoms (OR: 1.46; 95% CI 1.07, 1.98; p = 0.016). This three-way interaction was not significant for IL-6, IL-1ß, or TNF-α. For women in midlife with exposure to high adverse childhood experiences and multiple current life stressors, elevated levels of CRP were uniquely associated with clinically significant depression symptoms. Early life adversity and current life stressors represent identifiable individual risk factors whose negative impact may be curtailed with inventions to target inflammation in midlife women.

Relationship of Decisional Conflict About Driving Habits Between Older Adult Drivers and Their Family Members and Close Friends.

This study examines the relationship of decisional conflict about driving habits between older adult drivers (≥70 years old) and their family members and close friends. This secondary analysis utilizes data originating from a multi-site randomized controlled trial assessing the effect of a driving decision aid (DDA) intervention. Decisional conflict about stopping or changing driving habits for drivers was measured with the Decisional Conflict Scale (DCS). Dyadic associations between drivers' and study partners' (SPs') DCS scores were analyzed using an actor-partner interdependence model. Among 228 driver-SP dyads, Dyadic DCS was correlated at baseline (r = .18, p < .01), and pre-intervention DCS was associated with post-intervention DCS (p < .001 for SPs [ß = .73] and drivers [ß = .73]). Drivers' baseline DCS and SPs' post-intervention DCS were slighly correlated (ß = .10; p = .036). Higher decisional conflict about driving among older drivers is frequently shared by their SPs. Shared decisional conflict may persist beyond intervening to support decision-making about driving cessation.

Harnessing technology to improve sleep in frontline healthcare workers: A pilot study of electronic noise-masking earbuds on subjective and objective sleep measures.

Objective: This pilot study assessed the effects of electronic noise-masking earbuds on subjective sleep perception and objective sleep parameters among healthcare workers (HCWs) reporting sleep difficulties during the COVID-19 pandemic. Methods: Using a pre-post design, 77 HCWs underwent 3 nights of baseline assessment followed by a 7-night intervention period. Participants wore an at-home sleep monitoring headband to assess objective sleep measures and completed subjective self-report assessments. The difference in mean sleep measures from baseline to intervention was estimated in linear mixed models. Results: Compared to baseline assessments, HCWs reported significant improvements in sleep quality as measured by the Insomnia Severity Index (ISI) (Cohen's d = 1.74, p < 0.001) and a significant reduction in perceived sleep onset latency (SOL) during the intervention (M = 17.2 minutes, SD = 7.7) compared to baseline (M = 24.7 minutes, SD = 16.1), (Cohen's d = -0.42, p = 0.001). There were no significant changes in objective SOL (p = 0.703). However, there was a significant interaction between baseline objective SOL (<20 minutes vs >20 minutes) and condition (baseline vs intervention) (p = 0.002), such that individuals with objective SOL >20 minutes experienced a significant decrease in objective SOL during the intervention period compared to baseline (p = 0.015). Conclusions: HCWs experienced a significant improvement in perceived SOL and ISI scores after using the electronic noise-masking earbuds. Our data provide preliminary evidence for a nonpharmacological intervention to improve the sleep quality of HCWs which should be confirmed by future controlled studies.

Natural vs. Surgical Postmenopause and Psychological Symptoms Confound the Effect of Menopause on Executive Functioning Domains of Cognitive Experience.

Objective: The menopause transition is associated with difficulties in executive function. However, it is unclear whether these difficulties persist past perimenopause. This study investigated whether potential confounders, including natural vs. surgical postmenopause and menopause-related psychological symptoms, influence whether executive dysfunction persists into postmenopause. Study Design: A cross-sectional sample of women aged 35-65 years (N = 1971) in one of four groups, premenopause, perimenopause, natural postmenopause, and surgical postmenopause, were surveyed. Participants self-reported executive functioning with the Brown Attention Deficit Disorder Scale (BADDS), anxiety symptom severity with the Generalized Anxiety Disorder Questionnaire (GAD-7), and depression symptom severity with the Center for Epidemiologic Studies Depression Scale (CES-D). Main Outcome Measures: We analyzed the association between group and BADDS scores using linear regression models - first, by controlling for age, education, and self-reported attention deficit hyperactivity disorder (ADHD) diagnosis (Model #1) and, second, by further controlling for current difficulty sleeping, anxiety, and depression (Model #2). Results: In both models, BADDS scores were significantly elevated (indicating more difficulties in executive function) among women in the perimenopausal and surgical postmenopausal groups compared with those in the premenopausal group. Likewise, the perimenopausal and surgical postmenopausal groups had the highest proportions of participants who reported difficulty sleeping and clinical levels of anxiety and depression. BADDS scores were significantly higher in natural postmenopausal vs. premenopausal women without controlling for difficulty sleeping, anxiety, and depression (Model #1), but not when adjusting for these variables (Model #2). Conclusions: The type of menopause and psychological symptoms are important confounders of the relationship between the menopause transition and executive dysfunction, and help explain whether executive dysfunction persists or recovers in postmenopause.Reprinted from Maturitas 2023; 170:64-73, with permission from Elsevier. Copyright © 2023.

Sex differences in stress-induced cortisol response among infants of mothers exposed to childhood adversity.

BACKGROUND: Adverse childhood experiences (ACEs) increase risk for mental illness in women and their children, and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may play a role. The impact of ACEs on the HPA axis may be strongest when ACEs occur prepubertally and in those exposed to abuse ACEs. METHODS: To test this, we measured salivary cortisol in 96 mother-infant dyads while mothers were separated from their infant experiencing a laboratory stressor. Mothers completed the ACE questionnaire, ACEs occurring prepubertally (pACEs) were measured, and mother-infant dyads were grouped based on maternal pACE history: no pACEs, 1+ pACEs with abuse, or 1+ pACEs but no abuse. RESULTS: Mothers with 1+ pACEs exhibited decreases in cortisol (relative to pre-infant stressor), which differed significantly from the cortisol increase mothers with no pACEs experienced, regardless of abuse presence (p=.001) or absence (p=.002). These 1+ pACE groups did not differ from one another (p=.929). Significant sex differences in infant cortisol were observed in infants of mothers with 1+ pACEs (regardless of abuse) but not in infants of mothers with no pACEs. When mothers had 1+ pACEs, males showed decreases in cortisol in response to a stressor whereas females demonstrated increases, and males and females differed significantly when their mothers had 1+ pACEs with (p=0.025) and without (p=0.032) abuse. CONCLUSIONS: Regardless of maternal exposure to childhood abuse, in response to a stressor, prepubertal ACEs were associated with lower cortisol response in mothers and sex differences in six-month-old infants, with males showing a lower cortisol response than females.

Project Safe Guard: Challenges and opportunities of a universal rollout of peer-delivered lethal means safety counseling at a US military installation.

INTRODUCTION: The US Department of Defense recommends lethal means safety counseling (LMSC) to promote firearm injury prevention via secure storage of personal firearms. We describe the rollout of a universal, peer-delivered adaptation of Project Safe Guard (PSG)-a brief, single-session LMSC discussion-at a US Space Force installation. METHOD: Program evaluation data were collected via anonymous, voluntary, and online surveys. Of approximately 862 eligible active-duty service members and embedded civilians, 324 completed the preprogram survey and 68 and 37 completed the 1- and 2-month follow-ups, respectively. RESULTS: At preprogram, 69.1% agreed that peer-delivered LMSC is appropriate. After rollout, 100% of the 222 firearm locking devices available to service members were requested from the on-base Violence Prevention Integrator. The effectiveness of PSG was indeterminable due to the low survey response rates. CONCLUSIONS: Despite strong preprogram support for peer-delivered LMSC and behavioral indicators of secure firearm storage (e.g., firearm locking device requests), several challenges limited the uptake and evaluability of the PSG program in this naturalistic environment, including military survey fatigue and competing mission priorities. Additional work is needed to determine the effectiveness of peer-delivered LMSC in a military context. Sustained base support and military-civilian collaborations will be critical.

Migraine headaches are associated with motor vehicle crashes and driving habits among older drivers: Prospective cohort study.

BACKGROUND: Migraine headache is common in older adults, often causing symptoms that may affect driving safety. This study examined associations of migraine with motor vehicle crashes (MVCs) and driving habits in older drivers and assessed modification of associations by medication use. METHODS: In a multi-site, prospective cohort study of active drivers aged 65-79 (53% female), we assessed prevalent migraine (i.e., ever had migraine, reported at enrollment), incident migraine (diagnosis first reported at a follow-up visit), and medications typically used for migraine prophylaxis and treatment. During 2-year follow-up, we recorded self-reported MVCs and measured driving habits using in-vehicle GPS devices. Associations of prevalent migraine with driving outcomes were estimated in multivariable mixed models. Using a matched design, associations of incident migraine with MVCs in the subsequent year were estimated with conditional logistic regression. Interactions between migraine and medications were tested in all models. RESULTS: Of 2589 drivers, 324 (12.5%) reported prevalent migraine and 34 (1.3%) incident migraine. Interactions between migraine and medications were not statistically significant in any models. Prevalent migraine was not associated with MVCs in the subsequent 2 years (adjusted OR [aOR] = 0.98; 95% CI: 0.72, 1.35), whereas incident migraine significantly increased the odds of having an MVC within 1 year (aOR = 3.27; 1.21, 8.82). Prevalent migraine was associated with small reductions in driving days and trips per month and increases in hard braking events in adjusted models. CONCLUSION: Our results suggest substantially increased likelihood of MVCs in the year after newly diagnosed migraine, indicating a potential need for driving safety interventions in these patients. We found little evidence for MVC risk or substantial changes in driving habits associated with prevalent migraine. Future research should examine timing, frequency, and severity of migraine diagnosis and symptoms, and use of medications specifically prescribed for migraine, in relation to driving outcomes.