Esterov, Dmitry

Abstract Background Post-traumatic headache (PTH) is a common acute and persistent symptom following mild traumatic brain injury (mTBI). Symptoms of cutaneous allodynia and presence of nociceptive sensitization might be associated with acute PTH and its persistence. The objectives of this study were to compare allodynia symptoms and cutaneous heat pain thresholds amongst males and females with acute PTH to healthy controls (HC) and determine if pain thresholds and allodynia symptoms are associated with PTH outcomes. Methods This prospective longitudinal study enrolled 139 adults with acute PTH attributed to mTBI as defined by the International Classification of Headache Disorders and 95 HC. All PTH participants completed a baseline research visit near PTH onset and a follow-up visit three to four months later. All PTH participants and a subset of HC completed the Allodynia Symptom Checklist (ASC-12) at each research visit. A different subset of the participants underwent quantitative sensory testing (QST) during baseline, 4-week, and 16-week research visits to quantify cutaneous heat pain thresholds at the forehead and forearms. Data from daily headache diaries were used to determine longitudinal PTH improvement versus non-improvement at three months. ASC-12 score and pain threshold comparisons were made between PTH and HC groups, PTH improved versus non-improved cohorts, and between PTH males and females. Results Participants with PTH had an average age of 42.6 years and 64.0% were female. HC had an average age of 40.0 years and 65.3% were female. At the first visit, PTH participant ASC-12 scores averaged 3.6 versus 0.1 amongst HC, p < 0.001. 44.8% of PTH participants had headache improvement at 3 months. ASC-12 scores were higher in the PTH non-improved versus improved group at baseline (4.0 versus 2.4, p = 0.038) and 3-month follow-up (3.4 versus 1.9, p = 0.012). ASC-12 scores were higher in females than males at baseline (4.7 versus 1.6, p < 0.001) and 3-months (3.9 versus 1.2, p < 0.001). Cutaneous heat pain thresholds at the forehead and forearm did not differ between any group. Conclusions PTH attributed to mTBI is associated with symptoms of cutaneous allodynia. Greater allodynia symptoms are present in females with PTH compared to males and may be associated with PTH non-improvement.

Objective To study the reliability and validity of adverse childhood experiences (ACE) scores measured using a questionnaire versus abstraction of medical records, and to test whether the scores vary by history of bilateral oophorectomy, or by age and presence of anxiety or depressive symptoms at the time of questionnaire administration. Design The study involved a reliability component and a predictive validity component. Setting A population-based sample in Olmsted County, Minnesota, was derived from the Mayo Clinic Cohort Study of Oophorectomy and Aging-2. Participants We included 198 women who underwent premenopausal bilateral oophorectomy for a non-malignant indication between 1988 and 2007 and 174 referent women of the same age randomly sampled from the general population (total of 372 women). At a later time (median of 22.7 years later), the women were contacted and invited to self-administer the ACE questionnaire during an inperson visit. Independent of the visit, their medical records were abstracted for ACE by a physician. Interventions Questionnaire and abstraction-based ACE scores. Main outcome measures Agreement between the two ACE scores (reliability; weighted kappa statistics) and comparison of incidence of multimorbidity in women with ACE scores ≥1 vs 0 (predictive validity; survival analyses). Data were analysed in March and April 2024. Results The 372 women in the study had a median age of 65 years at the time of ACE questionnaire self-administration (IQR, 62–69). Questionnaire-based ACE scores showed moderate agreement with abstracted ACE scores (weighted kappa 0.44 (95% CI 0.34 to 0.54)). The cut-off score of ACE ≥1 showed an overall fair agreement between the two scores (kappa 0.33 (95% CI 0.24 to 0.43)). A comparison of the cumulative incidence of multimorbidity in women with an ACE score ≥1 versus women with ACE score of 0 yielded a HR of 1.13 (95% CI 1.00 to 1.27) for abstracted ACE and 1.13 (95% CI 1.01 to 1.27) for questionnaire-based ACE. The best predictive validity was for ACE measured by both methods combined (either or) with a HR of 1.29 (95% CI 1.13 to 1.46). Conclusions and relevance Questionnaire-based ACE scores have moderate agreement with medical records abstracted ACE scores. However, both sets of ACE scores are predictive of the accumulation of multimorbidity at older age and should be considered complementary.

Abstract The impact of early-life traumatic experiences on late-life morbidity remains partly unknown. We tested the hypothesis that adverse childhood experiences (ACE) and specifically abuse (physical, verbal or emotional, or sexual) experienced during childhood or early adulthood are associated with a higher rate of accumulation of multi-morbidity in women. Here we show strong evidence in support of the hypothesis. We studied 1,026 women aged 21–45 years randomly selected from the general population in Olmsted County, Minnesota and used the Rochester Epidemiology Project medical records-linkage system to measure the rate of development of 18 chronic conditions. The women had a median age of 41 years at inclusion in the study and were followed historically for a median of 21 years. Women with an ACE score ≥ 2 had higher incidence of 10 of the 18 chronic conditions considered separately and an accelerated accumulation of multi-morbidity measured as a score compared to women with ACE score 0. In addition, women exposed specifically to abuse in childhood or early adulthood had accelerated accumulation of multi-morbidity. We excluded the possible confounding effect of socioeconomic status and explored a series of possible mediation events or characteristics. We discuss several possible biological and social or behavioral mechanisms underlying these associations.

Abstract Background Persistent postural‐perceptual dizziness (PPPD) is a chronic functional vestibular disorder that is a potential sequela of traumatic brain injury (TBI). Currently, little is known about how patients with TBI associated PPPD respond to typical PPPD treatment modalities. Objective To investigate the prevalence of TBI as a precipitant for PPPD and assess outcomes of usual treatment. Design Retrospective cohort study. Setting Electronic medical records from a tertiary care center. Participants Patients ≥18 years of age diagnosed with PPPD secondary to TBI between January 2015 and December 2022 who underwent 6 months of treatment with at least one return clinic visit. Interventions Not applicable. Main Outcome Measure(s) Patients' best clinical global impression‐improvement scale (CGI‐I) score following 6 months of treatment were collected and then compared with previously published literature, with CGI‐I scores of 1 or 2 (indicating the patient was “very much” or “much” improved, respectively) considered treatment responders. Results In total, 134 (8.9%) of 1503 patients had a TBI as the triggering event for PPPD. The mean age of this cohort was 47.6 years with most of these cases occurring after a mild TBI (85.8%). The proportion of females with post‐TBI PPPD (58.2%) was significantly lower than the proportion with PPPD due to all causes ( p < .037). The most common treatment prescribed was vestibular therapy (82.2%), and 53.3% of patients were considered treatment responders after 6 months. Patients with TBI‐induced PPPD had a significantly worse mean CGI‐I score (2.49 ± 1.1) when compared to prior literature (1.71 ± 0.83) ( p < .001). Conclusions This study found a 9% prevalence of PPPD following TBI in the largest cohort studied to date. Patients who developed PPPD following TBI did not respond as well to standard treatments as patients with other causes of the disorder, and thus may require closer clinical follow‐up to assess treatment efficacy.

The objective of this study was to understand whether exposure to adverse childhood experiences (ACEs) before 18 years of age predicts increased neurobehavioral symptom reporting in adults presenting for treatment secondary to persistent symptoms after mild traumatic brain injury (mTBI). This cross-sectional study identified 78 individuals with mTBI from 2014 to 2018 presenting for treatment to an outpatient multidisciplinary rehabilitation clinic. Neurobehavioral symptom inventory (NSI-22) scores were collected on admission, and ACEs for each patient were abstracted by medical record review. A linear regression model was used to assess if an individual who experienced at least one ACE before age 18 resulted in significantly different neurobehavioral scores compared with those not reporting any history of an ACE before age 18. Participants who reported at least one ACE before age 18 had significantly increased NSI-22 scores on admission to the rehabilitation clinic compared with patients without history of ACEs (mean difference 10.1, p = 0.011), adjusted for age and gender. For individuals presenting for treatment after mTBI, a history of ACEs before age 18 was associated with increased neurobehavioral symptoms.

This study sought to identify whether an anatomical indicator of injury severity as measured by multiparametric magnetic resonance imaging (MRI) including magnetic resonance elastography (MRE), is predictive of a clinical measure of injury severity after moderate-severe traumatic brain injury (TBI). Nine individuals who were admitted to acute inpatient rehabilitation after moderate-to-severe TBI completed a comprehensive MRI protocol prior to discharge from rehabilitation, which included conventional MRI with diffusion tensor imaging (DTI). Of those, five of nine also underwent brain MRE to measure the brain parenchyma stiffness. Clinical severity of injury was measured by the length of post-traumatic amnesia (PTA). MRI-assessed non-hemorrhage contusion score and hemorrhage score, DTI-measured white matter fractional anisotropy, and MRE-measured lesion stiffness were all assessed. A higher hemorrhagic score was significantly associated with a longer length of PTA ( p = 0.026). Participants with a longer PTA tended to have a higher non-hemorrhage contusion score and softer contusion lesions than the contralateral control side, although the small sample size did not allow for assessment of a significant association. To our knowledge, this is the first report applying MRI/MRE imaging protocol to quantitate altered brain anatomy after moderate-severe TBI and its association with PTA, a known clinical predictor of post-acute outcome. Future larger studies could lead to the development of prediction models that integrate clinical data with anatomical (MRI), structural (DTI), and mechanical (MRE) changes caused by TBI, to inform prognosis and care planning.

AbstractBackgroundPatients in the intensive care unit (ICU) often experience extended periods of immobility. Following hospital discharge, many face impaired mobility and never return to their baseline function. Although the benefits of physical and occupational rehabilitation are well established in non‐ICU patients, a paucity of work describes effective practices to alleviate ICU‐related declines in mobility.ObjectiveTo assess how rehabilitation with physical and occupational therapy (PT‐OT) during ICU stays affects patients' mobility, self‐care, and length of hospital stay.DesignRetrospective cohort study.SettingInpatient ICU.ParticipantsA total of 6628 adult patients who received physical rehabilitation across multiple sites (Arizona, Florida, Minnesota, and Wisconsin) of a single institution between January 2018 and December 2021.InterventionsNot applicable.Main Outcome MeasuresDescriptive statistics, linear regression models, and gradient boosting machine methods were used to determine the relationship between the amount of PT‐OT received and outcomes of hospital length of stay (LOS), Activity Measure for Post‐Acute Care Daily Activity and Basic Mobility scores.ResultsThe 6628 patients who met inclusion criteria received an average (median) of 23 (range: 1‐89) minutes of PT‐OT per day. Regression analyses showed each additional 10 minutes of PT‐OT per day was associated with a 1.0% (95% confidence interval [CI]: 0.41–1.66, p < .001) higher final Basic Mobility score, a 1.8% (95% CI: 1.30%–2.34%, p < .001) higher final Daily Activity score, and a 1.2‐day (95% CI: −1.28 to −1.09, p < .001) lower hospital LOS. One‐dimensional partial dependence plots revealed an exponential decrease in predicted LOS as minutes of PT‐OT received increased.ConclusionHigher rehabilitation minutes provided to patients in the ICU may reduce the LOS and improve patients' functional outcomes at discharge. The benefits of rehabilitation increased with increasing amounts of time of therapy received.

Abstract Objective To conduct a scoping review of models of care for chronic disease management to identify potentially effective components for management of chronic traumatic brain injury (TBI). Methods Information sources : Systematic searches of three databases (Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews) from January 2010 to May 2021. Eligibility criteria : Systematic reviews and meta‐analyses reporting on the effectiveness of the Chronic Care Model (CCM), collaborative/integrated care, and other chronic disease management models. Data : Target diseases, model components used ( n = 11), and six outcomes (disease‐specific, generic health‐related quality of life and functioning, adherence, health knowledge, patient satisfaction, and cost/health care use). Synthesis : Narrative synthesis, including proportion of reviews documenting outcome benefits. Results More than half (55%) of the 186 eligible reviews focused on collaborative/integrated care models, with 25% focusing on CCM and 20% focusing on other chronic disease management models. The most common health conditions were diabetes ( n = 22), depression ( n = 16), heart disease ( n = 12), aging ( n = 11), and kidney disease ( n = 8). Other single medical conditions were the focus of 22 reviews, multiple medical conditions of 59 reviews, and other or mixed mental health/behavioral conditions of 20 reviews. Some type of quality rating for individual studies was conducted in 126 (68%) of the reviews. Of reviews that assessed particular outcomes, 80% reported disease‐specific benefits, and 57% to 72% reported benefits for the other five types of outcomes. Outcomes did not differ by the model category, number or type of components, or target disease. Conclusions Although there is a paucity of evidence for TBI per se, care model components proven effective for other chronic diseases may be adaptable for chronic TBI care.

BACKGROUND: Practice guidelines and research results emphasize the need for dyadic interventions targeting psychosocial outcomes such as depression, anxiety, social function, physical function, and health-related quality of life. Resilience interventions have been proposed as one strategy to influence these outcomes. OBJECTIVE: The objective of this observational pilot study was to determine the feasibility and acceptability of the Resilient Living program among persons with stroke or brain tumor (BT) admitted for comprehensive acute inpatient rehabilitation and/or their family caregivers. A secondary aim was to gather preliminary data to assess the effects of the program on quality of life, stress, anxiety, physical function, sleep disturbance, fatigue, resilience, dyadic coping, and caregiver role overload. METHODS: The Resilient Living program is a psychosocial intervention with a focus on building resilience skills. Feasibility and acceptability outcomes were assessed at the end of the study. Quantitative outcome measures were collected at baseline, 12 weeks, and 6 months post the intervention. RESULTS: Eight patients and eight caregivers completed the study. The intervention was feasible with this population. Participants found the intervention useful and appreciated the flexibility of an online program; however, finding time to engage in it was challenging. Recruitment of eligible patients with acquired brain disorders and their caregivers as a dyad was challenging. CONCLUSION: The study confirms prior research suggesting that interventions targeting resilience are feasible, but larger studies with more rigorous methods are needed to appreciate the influence of resilience interventions in persons with brain disorders and their caregivers. Further research is needed to identify the characteristics of those most likely to benefit from resilience interventions and the optimal timing of such interventions.