The impact of resilience on headache disability as measured by the Migraine Disability Assessment (MIDAS).

OBJECTIVE: Our objectives were to examine cross-sectional correlations of headache disability with measures of resilience, anxiety, and depression, and to determine if resilience modified the association between headache severity/frequency and disability. BACKGROUND: Resilience is associated with quality of life and functioning among patients with chronic conditions. We investigated whether resilience strongly mitigates headache-related disability as measured by the Migraine Disability Assessment (MIDAS). METHODS: We prospectively recruited 160 patients with primary headache disorders seen in a tertiary headache medicine program between February 20, 2018 and August 2, 2019. Each participant completed the MIDAS, Conner Davidson Resilience Scale (CDRS-25), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and WHO-5 Well-Being Index. RESULTS: The CDRS-25 score was negatively correlated with the total MIDAS (r = -0.21, p = 0.009), GAD-7 (r = -0.56, p < 0.001), and PHQ-9 scores (r = -0.34, p < 0.001). Well-being inversely correlated with disability (r = -0.37, p < 0.001). Increases in anxiety and depression increased the odds of disability. A 1 point increase in the CDRS-25 score decreased the odds of being severely disabled by 4% (OR = 0.96, 95% CI: 0.94 to 0.99, p = 0.001). However, the CDRS-25 score did not significantly moderate the association between headache days and disability. CONCLUSION: Traits associated with resilience decreased the odds of severe disability from headaches, whereas anxiety, depression, and headache frequency were strongly associated with higher disability from headache.

Evaluation of a Novel Wellness Curriculum on Medical Student Wellbeing and Engagement Demonstrates a Need for Student-Driven Wellness Programming.

PROBLEM: Medical training is stressful and has well-established implications for student wellbeing. Despite widespread efforts to reduce student burnout through wellness programming in medical schools, there is a paucity of literature examining students' perception of wellness and engagement with these programs. As such, we sought to evaluate: 1) medical students' level of engagement with a multifaceted wellness curriculum, 2) factors students perceived as important to wellbeing, and 3) associations with longitudinal measures of wellbeing and perceived stress. Intervention: A multipronged wellness curriculum was instituted at Mayo Clinic Alix School of Medicine-AZ (MCASOM-AZ) in 2017. This includes mental health services, curriculum-embedded seminars, wellness committee (composed of students, faculty, and administration) driven programming, and student proposed wellness activities that are reviewed and funded by the committee. The authors invited students at our institution to complete questionnaires at three timepoints during the 2018-2019 academic year. Questionnaires asked participants to rank eight factors from least to most important to their overall wellbeing. Participants self-reported their participation in each prong of the wellness curriculum and ranked the impact of each on their overall wellbeing. Their wellbeing and perceived stress were measured at each timepoint using validated psychological instruments. Context: As MCASOM-AZ opened in 2017, the student body at the time of study consisted of first- and second-year medical students. All students had the opportunity to engage with all aspects of the wellness curriculum and participate in this study, however participation was elective and all responses were anonymous. Of the MCASOM-AZ student body comprised of 100 students, 58 consented to participate in the study, 41.4% of which were Year 1 and 58.6% of which were Year 2 students. Participant age and gender were collected and were representative of the larger student body. Impact: Students engaged most with student-initiated wellness. They perceived unscheduled time as most impactful to their overall wellbeing with student-initiated activities as second-most impactful. Students with higher perceived stress were more likely than others to use mental health resources, which otherwise ranked lower in importance. Ranking academic performance as important to wellbeing was associated with higher wellbeing. There was no difference in wellbeing between students who participated in the wellness curriculum and those who did not. However, overall student wellbeing increased over the course of the year while perceived stress decreased. Lessons Learned: Medical school programs may benefit from allowing students to direct or contribute to the design of their own wellness curriculum. Additionally, medical education should work toward creating a more supportive learning environment with improved flexibility in order to better meet students' individual needs without compromising their education. Despite having low utilization rates overall, mental health resources remain an important aspect of student support services as they are used by students under greater amounts of perceived stress than their peers.Supplemental data for this article is available online at https://doi.org/10.1080/10401334.2021.2004415 .

An Agitated Patient With COVID-19 Infection and Early-onset Alzheimer Disease.

Encephalopathy, delirium, and agitation are documented symptoms of coronavirus disease (COVID-19) infection, but research into the management of agitation in the setting of COVID-19 and pre-existing neuropsychiatric disease is ongoing. We present a 55-year-old male patient with early-onset Alzheimer disease and deteriorating mental and functional status who presented to our institution with agitation and persistent COVID-19 positivity on polymerase chain reaction testing. His agitation was improved through pharmacologic optimization including the avoidance of benzodiazepines and initiation of clonidine and prazosin, which temporally coincided with the resolution of his nearly 2-month long COVID-19 positivity.

Medical students describe their wellness and how to preserve it.

BACKGROUND: Despite widespread efforts to create wellness programming in medical schools, there is a paucity of literature examining students' perception of wellness and perceptions of these programs. With the inaugural class at the Arizona campus of Mayo Clinic Alix School of Medicine (MCASOM-AZ), an opportunity arose to establish an empirically evaluated wellness curriculum that most inclusively and effectively enables medical students to flourish for years to come. The initial wellness offerings included mental health, academic success, and disability services, curriculum-embedded seminars, wellness committee driven programming, and student-proposed wellness activities. We aimed to improve the relevance and impact of medical school wellness curricula by soliciting in-depth and longitudinal perspectives of medical students themselves. As MCASOM-AZ opened in 2017, the student body at the time of study consisted of first- and second-year medical students. METHODS: Employing a mixed methods analysis of qualitative and longitudinal quantitative data, first- and second-year students at a MCASOM-AZ were invited to respond to an anonymous, online year-long survey (baseline, six months and 12 months) during the 2018-2019 academic year and participate in a structured, in-depth and in-person, peer-to-peer interview about their conceptions of wellness and the MCASOM-AZ wellness curriculum and resources. Qualitative data was coded for themes using thematic analysis strategies by independent raters. RESULTS: Nearly half of eligible students completed the baseline survey,1/3 completed all 3 time-points, and 1/5 participated in an in-depth interview. Participant age, gender, and year of school were representative of the larger student body. Although individual conceptions varied, Wellness was consistently highly valued. Family, Academic Performance, and Friends emerged as most important to well-being across time-points. Academic work arose as the largest barrier to wellness. Analysis of qualitative data revealed five themes. Despite individual differences in approaches to wellness, wellbeing was interrelated to the learning environment; mandatory wellness efforts that didn't address the medical culture met with skepticism. CONCLUSIONS: Interview responses provided understanding and context by which to interpret questionnaire responses. Academics was critical to students' identity and wellness, while also the largest barrier. Suggested curricular improvements include restructuring academic work, seamlessly integrating wellness within coursework, and offering optional individualized approaches.

Parental leave policy information during residency interviews.

BACKGROUND: During interviews, medical students may feel uncomfortable asking questions that might be important to them, such as parental leave. Parental leave policies may be difficult for applicants to access without asking the program director or other interviewers. The goal of this study is to evaluate whether parental leave information is presented to prospective residents and whether medical students want this information. METHODS: Fifty-two program directors (PD's) at 3 sites of a single institution received a survey in 2019 to identify whether parental leave information is presented at residency interviews. Medical students received a separate survey in 2020 to identify their preferences. Fisher exact tests, Pearson χ2 tests and Cochran-Armitage tests were used where appropriate to assess for differences in responses. RESULTS: Of the 52 PD's, 27 responded (52%) and 19 (70%) indicated that information on parental leave was not provided to candidates. The most common reason cited was the belief that the information was not relevant (n = 7; 37%). Of the 373 medical students, 179 responded (48%). Most respondents (92%) wanted parental leave information formally presented, and many anticipated they would feel extremely or somewhat uncomfortable (68%) asking about parental leave. The majority (61%) felt that these policies would impact ranking of programs "somewhat" or "very much." CONCLUSIONS: Parental leave policies may not be readily available to interviewees despite strong interest and their impact on ranking of programs by prospective residents.

Lorazepam Challenge for Individuals at Varying Genetic Risk for Alzheimer Disease.

INTRODUCTION: This study set out to clarify the differential acute cognitive impact of lorazepam based on varying genetic risk for Alzheimer disease. METHODS: Fifty-seven cognitively unimpaired individuals aged 51 to 88, genotyped according to apolipoprotein E (APOE) and translocase of outer mitochondrial membrane (40 homolog) poly-T lengths, completed cognitive testing before, 2.5 and 5 hours after receiving a 1 mg dose of lorazepam. RESULTS: Post-lorazepam, there were significant (P<0.05) declines from baseline in memory, psychomotor processing speed, and executive function. At 2.5 hours, the magnitude of this lorazepam-induced cognitive change was significantly greater in the APOE3/4 group than in the APOE3/3 group for tests of working memory and visuospatial memory/executive function. At 5 hours postchallenge, verbal memory and working memory deficits persisted in the APOE3/4 group compared with the APOE3/3 group. At 5 hours after lorazepam challenge, as compared with the very long/very long group, the short/short group performed slightly worse on a test of working memory (P<0.05), but no other differences were observed among translocase of the outer mitochondrial membrane 40 homolog poly-T variant groups. DISCUSSION: The lorazepam challenge may be unmasking presymptomatic cognitive dysfunction associated with APOE4 carriage.

A resilience intervention involving mindfulness training for transplant patients and their caregivers.

Solid organ and stem cell transplant patients and their caregivers report a substantial level of distress. Mindfulness-based stress reduction has been shown to alleviate distress associated with transplant, but there is limited experience in this population with other mindfulness-based interventions, or with combined transplant patient and caregiver interventions. We evaluated a novel, 6-week mindfulness-based resilience training (MBRT) class for transplant patients and their caregivers that incorporates mindfulness practice, yoga, and neuroscience of stress and resilience. Thirty-one heart, liver, kidney/pancreas, and stem cell transplant patients and 18 caregivers at Mayo Clinic in Arizona participated. Measures of stress, resilience, depression, anxiety, health-related quality of life, positive and negative affect, and sleep were completed at baseline, 6 weeks, and 3 months postintervention. At 6 weeks and 3 months, patients demonstrated significant (P<.005) improvements from baseline in measures of perceived stress, depression, anxiety, and negative affect. Quality-of-life mental component (P=.006) and positive affect (P=.02) also improved at follow-up. Most participants adhered to the program, were satisfied with class length and frequency, and reported improved well-being as a result of the class. MBRT holds promise as an intervention to enhance resilience and manage stress for transplant patients and their caregivers.

Understanding and Promoting Resiliency in Patients with Chronic Headache.

Even among patients with the same type and severity of headache, there is considerable variability in functional outcomes. Some individuals are resilient, able to thrive despite pain, whereas others find that pain is an overwhelming burden that comes to define their lives. A substantial body of evidence suggests that patients' cognitive, emotional, and behavioral coping responses to their pain play a significant role in determining their long-term health. Resilient pain responses, which are shaped by both qualities of the individual and his/her social environment, can be learned and thus hold promise as targets for treatment. We draw on recent empirical findings that identify which pain beliefs, appraisals, and behaviors in response to pain are key to resilient and non-resilient coping among patients with chronic headache. We discuss how pain self-efficacy and pain acceptance set the stage for adaptive behaviors that have been linked to sustained well-being and good quality of life. We then describe psychosocial and behavioral interventions that show promise in promoting resilience among headache patients and conclude by considering areas ripe for further inquiry.

Studying ventricular abnormalities in mild cognitive impairment with hyperbolic Ricci flow and tensor-based morphometry.

Mild Cognitive Impairment (MCI) is a transitional stage between normal aging and dementia and people with MCI are at high risk of progression to dementia. MCI is attracting increasing attention, as it offers an opportunity to target the disease process during an early symptomatic stage. Structural magnetic resonance imaging (MRI) measures have been the mainstay of Alzheimer's disease (AD) imaging research, however, ventricular morphometry analysis remains challenging because of its complicated topological structure. Here we describe a novel ventricular morphometry system based on the hyperbolic Ricci flow method and tensor-based morphometry (TBM) statistics. Unlike prior ventricular surface parameterization methods, hyperbolic conformal parameterization is angle-preserving and does not have any singularities. Our system generates a one-to-one diffeomorphic mapping between ventricular surfaces with consistent boundary matching conditions. The TBM statistics encode a great deal of surface deformation information that could be inaccessible or overlooked by other methods. We applied our system to the baseline MRI scans of a set of MCI subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI: 71 MCI converters vs. 62 MCI stable). Although the combined ventricular area and volume features did not differ between the two groups, our fine-grained surface analysis revealed significant differences in the ventricular regions close to the temporal lobe and posterior cingulate, structures that are affected early in AD. Significant correlations were also detected between ventricular morphometry, neuropsychological measures, and a previously described imaging index based on fluorodeoxyglucose positron emission tomography (FDG-PET) scans. This novel ventricular morphometry method may offer a new and more sensitive approach to study preclinical and early symptomatic stage AD.

APOE ε4 Genotype and the Risk for Subjective Cognitive Impairment in Elderly Persons.

The authors compared the risk for subjective cognitive impairment (SCI) between carriers of the apolipoprotein E ε4 (APOE ε4) allele (cases) and APOE ε4 noncarriers (controls). SCI was assessed by a validated self-reported questionnaire. The authors used multivariable logistic regression analyses to compute odds ratios and 95% confidence intervals adjusted for age, sex, education, and marital status. Data were available on 114 participants (83 women; 47 APOE ε4 carriers; mean age, 69 years). The risk for SCI was significantly higher among cases than controls, particularly for those 70 years of age and older. These findings should be considered preliminary until confirmed by a prospective cohort study.

Role of theory of mind in emotional awareness and alexithymia: Implications for conceptualization and measurement.

The goal of this study was to determine whether alexithymia, which is characterized by difficulty in recognizing and describing emotions, is associated with impairments in the ability to mentally represent emotional states. We studied 89 outpatients including 29 conversion disorder patients, 30 functional somatic syndrome [e.g. fibromyalgia] patients and 30 medical controls. Groups did not differ on affective or cognitive Theory of Mind (ToM) measures, the Levels of Emotional Awareness Scale (LEAS) or the Twenty-Item Toronto Alexithymia Scale (TAS-20) after adjusting for Positive and Negative Affect Scale (PANAS) variables. Across all patients, LEAS but not TAS-20 correlated positively with affective and cognitive ToM measures after adjusting for PANAS scores. Impairments in ToM functioning influence LEAS performance but not TAS-20 scores. These findings support the distinction between a milder "anomia" form of alexithymia associated with impaired emotion naming and a more severe "agnosia" form associated with impaired mental representation of emotion.

Fibrillar amyloid correlates of preclinical cognitive decline.

BACKGROUND: It is not known whether preclinical cognitive decline is associated with fibrillar ß-amyloid (Aß) deposition irrespective of apolipoprotein E (APOE) ε4 status. METHODS: From a prospective observational study of 623 cognitively normal individuals, we identified all subjects who showed preclinical decline of at least 2 standard deviations beyond the decline of the entire group in memory or executive function. Fourteen decliners were matched by APOE ε4 gene dose, age, sex, and education with 14 nondecliners. Dynamic Pittsburgh compound B (PiB) positron emission tomography (PET) scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest were used to characterize and compare cerebral-to-cerebellar PiB distribution volume ratios (DVRs), reflecting fibrillar Aß burden. RESULTS: At P < .005 (uncorrected), decliners had significantly greater DVRs in comparison to nondecliners. CONCLUSIONS: Asymptomatic longitudinal neuropsychological decline is associated with subsequent increased fibrillar amyloid deposition, even when controlling for APOE ε4 genotype.

Associations between pituitary-ovarian hormones and cognition in recently menopausal women independent of type of hormone therapy.

OBJECTIVES: To examine associations of pituitary-ovarian hormone levels with cognition before and after different formulations of hormone therapy (HT) or placebo independent of treatment group. METHODS: Recently menopausal, healthy women were randomized to 0.45 mg/day oral conjugated equine estrogens (o-CEE, n = 109), 50 µg/day transdermal 17ß (tE2, n = 107) or placebo pills and patches (n = 146); women on active treatment received oral 200 mg/day micronized progesterone for 12 days per month. Levels of estrone, 17ß-estradiol, follicle stimulating hormone, luteinizing hormone, androstenedione, and testosterone were determined prior to and after 48 months of study participation. Neuropsychological testing was administered at baseline, and months 18, 36 and 48. Latent growth curve models controlling for education level, age, APOE allele status, waist circumference, and treatment examined the trajectories of each cognitive domain after accounting for the effect of hormone levels at baseline and months 18, 36 and 48. A linear multivariate mixed model examined the effect of changes in hormone levels on changes in trajectories of complex attention tasks with varying degrees of difficulty. RESULTS: All women were adherent to treatment at month 48. Higher baseline estrone levels were associated with poorer global cognition, auditory attention and working memory, visual attention, and executive function, but not working memory. Higher levels of baseline 17ß-E2 were associated with poorer cognitive performance, with marginal significance at baseline in speeded language and mental flexibility (p = 0.013). Other hormone levels were not associated with cognition. Controlling for all treatments, hormone levels at baseline and at month 48 did not have any significant correlation with cognitive trajectories over time. SUMMARY: In healthy, recently menopausal women, baseline estrone levels were inversely associated with selected cognitive factors independent of two types of HT or placebo during 4 years of follow-up. Baseline levels of the other pituitary-ovarian hormones studied were not associated with baseline cognition, nor were changes in any hormones associated with changes in cognition during the study. The marginal association between estradiol levels and cognitive factors warrants further investigation. GOV NUMBERS: NCT00154180, NCT00623311.

Comparing the effects of four common drug classes on the progression of mild cognitive impairment to dementia using electronic health records.

The objective of this study was to investigate the potential association between the use of four frequently prescribed drug classes, namely antihypertensive drugs, statins, selective serotonin reuptake inhibitors, and proton-pump inhibitors, and the likelihood of disease progression from mild cognitive impairment (MCI) to dementia using electronic health records (EHRs). We conducted a retrospective cohort study using observational EHRs from a cohort of approximately 2 million patients seen at a large, multi-specialty urban academic medical center in New York City, USA between 2008 and 2020 to automatically emulate the randomized controlled trials. For each drug class, two exposure groups were identified based on the prescription orders documented in the EHRs following their MCI diagnosis. During follow-up, we measured drug efficacy based on the incidence of dementia and estimated the average treatment effect (ATE) of various drugs. To ensure the robustness of our findings, we confirmed the ATE estimates via bootstrapping and presented associated 95% confidence intervals (CIs). Our analysis identified 14,269 MCI patients, among whom 2501 (17.5%) progressed to dementia. Using average treatment estimation and bootstrapping confirmation, we observed that drugs including rosuvastatin (ATE = - 0.0140 [- 0.0191, - 0.0088], p value < 0.001), citalopram (ATE = - 0.1128 [- 0.125, - 0.1005], p value < 0.001), escitalopram (ATE = - 0.0560 [- 0.0615, - 0.0506], p value < 0.001), and omeprazole (ATE = - 0.0201 [- 0.0299, - 0.0103], p value < 0.001) have a statistically significant association in slowing the progression from MCI to dementia. The findings from this study support the commonly prescribed drugs in altering the progression from MCI to dementia and warrant further investigation.

Confirming psychogenic nonepileptic seizures with video-EEG: sex matters.

The influence of gender on psychogenic nonepileptic seizures (PNES) diagnosis was examined retrospectively in 439 subjects undergoing video-EEG (vEEG) for spell classification, of whom 142 women and 42 men had confirmed PNES. The epileptologist's predicted diagnosis was correct in 72% overall. Confirmed epilepsy was correctly predicted in 94% men and 88% women. In contrast, confirmed PNES was accurately predicted in 86% women versus 61% men (p=0.003). Sex-based differences in likelihood of an indeterminate admission were not observed for predicted epilepsy or physiologic events, but were for predicted PNES (39% men, 12% women, p=0.0002). More frequent failure to record spells in men than women with predicted PNES was not explained by spell frequency, duration of monitoring, age, medication use, or personality profile. PNES are not only less common in men, but also more challenging to recognize in the clinic, and even when suspected more difficult to confirm with vEEG.

Integrating a Grassroots Well-Being Curriculum into a Radiation Oncology Residency Program.

PURPOSE: The burnout rate among US radiation oncology residents was 33% in 2016. To our knowledge there are no published interventions addressing burnout among radiation oncology residents. We describe the implementation of a well-being curriculum, cocreated by a psychologist, a medical humanities professional, and radiation oncology attending and resident physicians. METHODS AND MATERIALS: Radiation oncology residents at our institution were surveyed to determine themes that induced burnout. A curriculum was developed, with monthly small group sessions focused on 1 identified topic. Sessions alternated between psychological tool-focused approaches and humanities exercises. These were led by a psychologist or medical humanities professional. Residents were given protected time to attend sessions during business hours. Participation was optional. Participants were assigned a random identifier, and the Stanford Professional Fulfillment Index (PFI) was assessed at baseline and 3-month intervals. PFI trends were analyzed after 1 year. At the end of the year, a focus group was held to evaluate work satisfaction and self-reported interactions with patients and coworkers. This information was used to improve the curriculum. RESULTS: All 12 residents in the radiation oncology program participated in the curriculum. There was an equal number of residents of postgraduate years 2 through 5. Six of the participants were female. Of the participants, 11 completed the PFI. At baseline, 80% of residents met criteria for burnout. This decreased to 67%, 50%, and 33% at 3, 6, and 9 months, respectively. The proportion of residents meeting criteria for very good professional fulfillment was 30%, 56%, 38%, and 22% at baseline and 3, 6, and 9 months, respectively. On average, 9 of 12 residents attended each session. CONCLUSIONS: Our experience demonstrates the feasibility of collaborating with residents in the development of a well-being curriculum to cater programming to their needs, which we believe led to excellent engagement and attendance at each session.