Performance of a Claims-Based Frailty Proxy Using Varying Frailty Ascertainment Lookback Windows.

BACKGROUND: Frailty is an aging-related syndrome of reduced physiological reserve to maintain homeostasis. The Faurot frailty index has been validated as a Medicare claims-based proxy for predicting frailty using billing information from a user-specified ascertainment window. OBJECTIVES: We assessed the validity of the Faurot frailty index as a predictor of the frailty phenotype and 1-year mortality using varying frailty ascertainment windows. RESEARCH DESIGN: We identified older adults (66+ y) in Round 5 (2015) of the National Health and Aging Trends Study with Medicare claims linkage. Gold standard frailty was assessed using the frailty phenotype. We calculated the Faurot frailty index using 3, 6, 8, and 12 months of claims prior to the survey or all-available lookback. Model performance for each window in predicting the frailty phenotype was assessed by quantifying calibration and discrimination. Predictive performance for 1-year mortality was assessed by estimating risk differences across claims-based frailty strata. RESULTS: Among 4253 older adults, the 6 and 8-month windows had the best frailty phenotype calibration (calibration slopes: 0.88 and 0.87). All-available lookback had the best discrimination (C-statistic=0.780), but poor calibration. Mortality associations were strongest using a 3-month window and monotonically decreased with longer windows. Subgroup analyses revealed worse performance in Black and Hispanic individuals than counterparts. CONCLUSIONS: The optimal ascertainment window for the Faurot frailty index may depend on the clinical context, and researchers should consider tradeoffs between discrimination, calibration, and mortality. Sensitivity analyses using different durations can enhance the robustness of inferences. Research is needed to improve prediction across racial and ethnic groups.

Feasibility and Preliminary Effectiveness of an Online Meditation Intervention in Young Adults With Concussion History.

CONTEXT: Mindfulness interventions (yoga, meditation) in traumatic brain injury populations show promising improvements in injury outcomes. However, most studies include all injury severities and use in-person, general programming lacking accessibility and specificity to the nuance of concussion. Therefore, this study investigated the feasibility and preliminary effectiveness of an online, concussion-focused meditation intervention among young adults with a concussion history. DESIGN: Unblinded, single-arm, pilot intervention. METHODS: Fifteen young adults aged 18 to 30 with a concussion history within the past 5 years completed 10 to 20 minutes per day of online, guided meditations for 6 weeks. Feasibility was assessed using the Feasibility of Intervention Measure. Concussion symptoms were measured using the Rivermead Post-Concussion Symptom Questionnaire, perceived stress the Perceived Stress Scale-10, and mindfulness the Five Facet Mindfulness Questionnaire. Descriptive statistics described the study sample and determined intervention adherence and feasibility. Paired sample t tests were used to examine preintervention/postintervention changes in concussion symptoms, perceived stress, and mindfulness, with descriptive statistics further detailing significant t tests. RESULTS: Fifteen participants were enrolled, and 12 completed the intervention. The majority completed 5+ days per week of the meditations, and Feasibility of Intervention Measure (17.4 [1.8]) scores indicated high feasibility. Concussion symptom severity significantly decreased after completing the meditation intervention (11.3 [10.3]) compared with before the intervention (24.5 [17.2]; t[11] = 3.0, P = .01). The number of concussion symptoms reported as worse than before their concussion significantly decreased after completing the meditation intervention (2.7 [3.9]) compared with before the intervention (8.0 [5.7]; t[11] = 3.7, P = .004). Postintervention, 83.33% (n = 10) reported lower concussion symptom severity, and 75.00% (n = 9) reported less concussion symptoms as a mild, moderate, or severe problem (ie, worse than before injury). CONCLUSIONS: Findings suggest positive adherence and feasibility of the meditation intervention, with the majority reporting concussion symptom improvement postintervention. Future research is necessary to expand these pilot findings into a large trial investigating concussion-specific meditation programming.

Analysis of omega-3 and omega-6 polyunsaturated fatty acid metabolism by compound-specific isotope analysis in humans.

Natural variations in the 13C:12C ratio (carbon-13 isotopic abundance [δ13C]) of the food supply have been used to determine the dietary origin and metabolism of fatty acids, especially in the n-3 PUFA biosynthesis pathway. However, n-6 PUFA metabolism following linoleic acid (LNA) intake remains under investigation. Here, we sought to use natural variations in the δ13C signature of dietary oils and fatty fish to analyze n-3 and n-6 PUFA metabolism following dietary changes in LNA and eicosapentaenoic acid (EPA) + DHA in adult humans. Participants with migraine (aged 38.6 ± 2.3 years, 93% female, body mass index of 27.0 ± 1.1 kg/m2) were randomly assigned to one of three dietary groups for 16 weeks: 1) low omega-3, high omega-6 (H6), 2) high omega-3, high omega-6 (H3H6), or 3) high omega-3, low omega-6 (H3). Blood was collected at baseline, 4, 10, and 16 weeks. Plasma PUFA concentrations and δ13C were determined. The H6 intervention exhibited increases in plasma LNA δ13C signature over time; meanwhile, plasma LNA concentrations were unchanged. No changes in plasma arachidonic acid δ13C or concentration were observed. Participants on the H3H6 and H3 interventions demonstrated increases in plasma EPA and DHA concentration over time. Plasma δ13C-EPA increased in total lipids of the H3 group and phospholipids of the H3H6 group compared with baseline. Compound-specific isotope analysis supports a tracer-free technique that can track metabolism of dietary fatty acids in humans, provided that the isotopic signature of the dietary source is sufficiently different from plasma δ13C.

Translation of a Claims-Based Frailty Index From the International Classification of Diseases, Ninth Revision, Clinical Modification to the Tenth Revision.

The Faurot frailty index (FFI) is a validated algorithm that uses enrollment and International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based billing information from Medicare claims data as a proxy for frailty. In October 2015, the US health-care system transitioned from the ICD-9-CM to the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Applying the Centers for Medicare and Medicaid Services General Equivalence Mappings, we translated diagnosis-based frailty indicator codes from the ICD-9-CM to the ICD-10-CM, followed by manual review. We used interrupted time-series analysis of Medicare data to assess the comparability of the pre- and posttransition FFI scores. In cohorts of beneficiaries enrolled in January 2015-2017 with 8-month frailty look-back periods, we estimated associations between the FFI and 1-year risk of aging-related outcomes (mortality, hospitalization, and admission to a skilled nursing facility). Updated indicators had similar prevalences as pretransition definitions. The median FFI scores and interquartile ranges (IQRs) for the predicted probability of frailty were similar before and after the International Classification of Diseases transition (pretransition: median, 0.034 (IQR, 0.02-0.07); posttransition: median, 0.038 (IQR, 0.02-0.09)). The updated FFI was associated with increased risks of mortality, hospitalization, and skilled nursing facility admission, similar to findings from the ICD-9-CM era. Studies of medical interventions in older adults using administrative claims should use validated indices, like the FFI, to mitigate confounding or assess effect-measure modification by frailty.

Systemic inflammation and menstrual cycle length in a prospective cohort study.

BACKGROUND: Local inflammation plays an important role in normal folliculogenesis and ovulation, and conditions of chronic systemic inflammation, such as obesity and polycystic ovarian syndrome, can disrupt normal follicular dynamics. OBJECTIVE: This study aimed to determine the association between systemic inflammation, as measured by C-reactive protein levels, and menstrual cycle length. STUDY DESIGN: This study was a secondary analysis using data from Time to Conceive, a prospective time-to-pregnancy cohort study. The association between cycle length and C-reactive protein was analyzed using multivariable linear mixed and marginal models adjusted for age, race, education, body mass index, time since oral contraceptive use, alcohol, smoking, caffeine consumption, and exercise. Time to Conceive enrolled women aged 30 to 44 years with no history of infertility who were attempting to conceive for <3 months. Serum C-reactive protein levels were measured on cycle day 2, 3, or 4. Participants recorded daily menstrual cycle data for ≤4 months. RESULTS: Main outcome measures included menstrual cycle length and follicular and luteal phase lengths. Multivariable analysis included 1409 cycles from 414 women. There was no linear association between C-reactive protein levels and menstrual cycle length. However, compared with <1 mg/L, a C-reactive protein level >10 mg/L was associated with >3 times the odds (adjusted odds ratio, 3.7; 95% confidence interval, 1.67-8.11) of long cycles (defined as ≥35 days). When evaluating follicular phase length, a C-reactive protein level of >10 mg/L was associated both with follicular phases that were 1.7 (95% confidence interval, 0.23-3.09) days longer and with >2 times the odds of a long follicular phase (adjusted odds ratio, 2.2; 95% confidence interval, 1.05-4.74). CONCLUSION: There is a potential pathophysiological association between systemic inflammation and menstrual cycle changes. Further studies are needed to determine if systemic inflammation alters the menstrual cycle or if long menstrual cycles are a marker for elevated systemic inflammation.

Leukocyte inflammatory phenotype and function in migraine patients compared with matched non-migraine volunteers: a pilot study.

BACKGROUND: Migraine is a neurological condition characterized by chronic inflammation. However, not much is known about the potential role of peripheral blood immune cells in the pathophysiology of migraine. METHODS: We investigated the status of peripheral blood immune cells of 15 adults with frequent episodic or chronic migraine recruited chronologically from a randomized clinical trial (RCT) on Nutrition for Migraine (NCCIH 5R01AT007813-05) and 15 non-migraine, healthy volunteers (control) matched by age, gender, and Body Mass Index (BMI). Continuous variables were presented as means ± standard deviationas well as medians, and comparisons between patients and healthy volunteers were performed with non-parametric Wilcoxon signed rank tests. Statistical analysis was performed using Stata (StataCorp. 2019. Stata Statistical Software). Fluorescence-Activated Cell Sorting (FACS) data were processed using FlowJo software (Ashland, OR: Becton, Dickenson and Company; 2019). RESULTS: We observed that migraineurs had a significantly lower percentage of non-classical monocytes (CD14+CD16++) in blood circulation, compared to the control group. In addition, Migraineurs also showed a significantly lower percentage of blood CD3+CD4+ helper T cells and CD4+CD25+ regulatory T cells, compared to controls. Differences in leukocyte surface markers between chronic migraine patients and their matched controls were more prominent than those between episodic migraine patients and their matched controls. CONCLUSIONS: Our results suggest that migraine is associated with dysregulated peripheral immune homeostasis and that inflammation and autoimmunity may play a role in its pathophysiology.

Comparing prospective headache diary and retrospective four-week headache questionnaire over 20 weeks: Secondary data analysis from a randomized controlled trial.

BACKGROUND: Headache diaries and recall questionnaires are frequently used to assess headache frequency and severity in clinical and research settings. METHODS: Using 20 weeks of data from an intervention trial with 182 participants, we evaluated concordance between an electronic headache diary administered on a daily basis and designed to capture the presence and severity of headaches on an hourly basis (the headache diary) and a recall questionnaire, with retrospective estimation of the number of headache days assessed on a monthly basis. We further examined whether the duration or severity of headaches assessed by the electronic diary impacted concordance between these two measures. RESULTS: Over the course of four 28-day periods, people with migraine participating in a dietary intervention reported an average of 13.7 and 11.1 headache days in the headache diary and recall questionnaire, respectively. CONCLUSION: Over time, the concordance between headache days reported in these two measures tended to increase; however, the recall questionnaire headache estimates were lower than the diary measures in all four periods. When analysis was restricted to headaches lasting 8 hours or more, the number of headache days was more closely aligned with days reported in the recall questionnaire, indicating that the accuracy of recall estimates is likely to be influenced by headache duration. Restriction of analyses to moderate-to-severe headaches did not change results as much as headache duration. The findings indicate that recall questionnaires administered on a monthly basis may underestimate headache frequency and therefore should not be used interchangeably with headache diaries.Clinical Trials.gov Identifier: NCT02012790.

Comparison of Medicare Claims-based Proxy Measures of Poor Function and Associations With Treatment Receipt and Mortality in Older Colon Cancer Patients.

BACKGROUND: Multiple claims-based proxy measures of poor function have been developed to address confounding in observational studies of drug effects in older adults. We evaluated agreement between these measures and their associations with treatment receipt and mortality in a cohort of older colon cancer patients. METHODS: Medicare beneficiaries age 66+ diagnosed with stage II-III colon cancer were identified in the Surveillance, Epidemiology, and End Results-Medicare database (2004-2011). Poor function was operationalized by: (1) summing the total poor function indicators for each model; and (2) estimating predicted probabilities of poor function at diagnosis. Agreement was evaluated using Fleiss' κ and Spearman's correlation. Associations between proxy measures and: (1) laparoscopic versus open surgery; (2) chemotherapy versus none; (3) 5-fluorouracil (5FU)+oxaliplatin (FOLFOX) versus 5FU monotherapy; and (4) 1-year mortality were estimated using log-binomial regression, controlling for age, sex, stage, and comorbidity. Survival estimates were stratified by functional group, age, and comorbidity. RESULTS: Among 29,687 eligible colon cancer patients, 67% were 75+ years and 45% had stage III disease. Concordance across the poor function indicator counts was moderate (κ: 0.64) and correlation of predicted probability measures varied (ρ: 0.21-0.74). Worse function was associated with lower chemotherapy and FOLFOX receipt, and higher 1-year mortality. Within age and comorbidity strata, poor function remained associated with mortality. CONCLUSIONS: While agreement varied across the claims-based proxy measures, each demonstrated anticipated associations with treatment receipt and mortality independent of comorbidity. Claims-based comparative effectiveness studies in older populations should consider applying one of these models to improve confounding control.

Are prediction models for vaginal birth after cesarean accurate?

BACKGROUND: The use of trial of labor after cesarean delivery calculators in the prediction of successful vaginal birth after cesarean delivery gives physicians an evidence-based tool to assist with patient counseling and risk stratification. Before deployment of prediction models for routine care at an institutional level, it is recommended to test their performance initially in the institution's target population. This allows the institution to understand not only the overall accuracy of the model for the intended population but also to comprehend where the accuracy of the model is most limited when predicting across the range of predictions (calibration). OBJECTIVE: The purpose of this study was to compare 3 models that predict successful vaginal birth after cesarean delivery with the use of a single tertiary referral cohort before continuous model deployment in the electronic medical record. STUDY DESIGN: All cesarean births for failed trial of labor after cesarean delivery and successful vaginal birth after cesarean delivery at an academic health system between May 2013 and March 2016 were reviewed. Women with a history of 1 previous cesarean birth who underwent a trial of labor with a term (≥37 weeks gestation), cephalic, and singleton gestation were included. Women with antepartum intrauterine fetal death or fetal anomalies were excluded. The probability of successful vaginal birth after cesarean delivery was calculated with the use of 3 prediction models: Grobman 2007, Grobman 2009, and Metz 2013 and compared with actual vaginal birth after cesarean delivery success. Each model's performance was measured with the use of concordance indices, Brier scores, and calibration plots. Decision curve analysis identified the range of threshold probabilities for which the best prediction model would be of clinical value. RESULTS: Four hundred four women met the eligibility criteria. The observed rate of successful vaginal birth after cesarean delivery was 75% (305/404). Concordance indices were 0.717 (95% confidence interval, 0.659-0.778), 0.703 (95% confidence interval, 0.647-0.758), and 0.727 (95% confidence interval, 0.669-0.779), respectively. Brier scores were 0.172, 0.205, and 0.179, respectively. Calibration demonstrated that Grobman 2007 and Metz vaginal birth after cesarean delivery models were most accurate when predicted probabilities were >60% and were beneficial for counseling women who did not desire to have vaginal birth after cesarean delivery but had a predicted success rates of 60-90%. The models underpredicted actual probabilities when predicting success at <60%. The Grobman 2007 and Metz vaginal birth after cesarean delivery models provided greatest net benefit between threshold probabilities of 60-90% but did not provide a net benefit with lower predicted probabilities of success compared with a strategy of recommending vaginal birth after cesarean delivery for all women . CONCLUSION: When 3 commonly used vaginal birth after cesarean delivery prediction models are compared in the same population, there are differences in performance that may affect an institution's choice of which model to use.

Controlling for Frailty in Pharmacoepidemiologic Studies of Older Adults: Validation of an Existing Medicare Claims-based Algorithm.

BACKGROUND: Frailty is a geriatric syndrome characterized by weakness and weight loss and is associated with adverse health outcomes. It is often an unmeasured confounder in pharmacoepidemiologic and comparative effectiveness studies using administrative claims data. METHODS: Among the Atherosclerosis Risk in Communities (ARIC) Study Visit 5 participants (2011-2013; n = 3,146), we conducted a validation study to compare a Medicare claims-based algorithm of dependency in activities of daily living (or dependency) developed as a proxy for frailty with a reference standard measure of phenotypic frailty. We applied the algorithm to the ARIC participants' claims data to generate a predicted probability of dependency. Using the claims-based algorithm, we estimated the C-statistic for predicting phenotypic frailty. We further categorized participants by their predicted probability of dependency (<5%, 5% to <20%, and ≥20%) and estimated associations with difficulties in physical abilities, falls, and mortality. RESULTS: The claims-based algorithm showed good discrimination of phenotypic frailty (C-statistic = 0.71; 95% confidence interval [CI] = 0.67, 0.74). Participants classified with a high predicted probability of dependency (≥20%) had higher prevalence of falls and difficulty in physical ability, and a greater risk of 1-year all-cause mortality (hazard ratio = 5.7 [95% CI = 2.5, 13]) than participants classified with a low predicted probability (<5%). Sensitivity and specificity varied across predicted probability of dependency thresholds. CONCLUSIONS: The Medicare claims-based algorithm showed good discrimination of phenotypic frailty and high predictive ability with adverse health outcomes. This algorithm can be used in future Medicare claims analyses to reduce confounding by frailty and improve study validity.

Weathering the seasons of cancer survivorship: mind-body therapy use and reported reasons and outcomes by stages of cancer survivorship.

PURPOSE: Mind-body therapies (MBTs), a subset of complementary and alternative medicine (CAM), are used by cancer survivors to manage symptoms related to their cancer experience. MBT use may differ by cancer survivorship stage (i.e., acute, short-term, long-term) because each stage presents varying intensities of medical activities, associated emotions, and treatment effects. We examined the relationship between MBT use and survivorship stage (acute <1 year; short-term 1 to 5 years; long-term >5 years since diagnosis) using the CAM supplement of the 2012 National Health Interview Survey. We also examined reported reasons for and outcomes of MBT use and frequency of MBT types. METHODS: The sample included cancer survivors (N = 3076) and non-cancer controls (N = 31,387). Logistic regression tested the relationship of MBT use and survivorship stage. Weighted percentages were calculated by survivorship stage for reported reasons and outcomes of use and frequency of MBT types. RESULTS: MBT use varied by cancer survivorship stage (p = 0.02): acute (8.3 %), short-term (15.4 %), long-term (11.7 %) survivorship and non-cancer controls (13.2 %). In the adjusted model, short-term survivors had 35 % greater odds of MBT use than did controls (95 % CI 1.00, 1.83). Reasons for and outcomes of MBT use varied among the survivorship stages, with more acute survivors reporting medical-related reasons and more short-term survivors reporting to manage symptoms. CONCLUSIONS: MBT may fulfill different symptom management needs at varying stages of survivorship. These findings can help inform supportive care services of survivors' use of MBT for symptom burden at each stage and the allocation of these services.

Using claims data to predict dependency in activities of daily living as a proxy for frailty.

PURPOSE: Estimating drug effectiveness and safety among older adults in population-based studies using administrative health care claims can be hampered by unmeasured confounding as a result of frailty. A claims-based algorithm that identifies patients likely to be dependent, a proxy for frailty, may improve confounding control. Our objective was to develop an algorithm to predict dependency in activities of daily living (ADL) in a sample of Medicare beneficiaries. METHODS: Community-dwelling respondents to the 2006 Medicare Current Beneficiary Survey, >65 years old, with Medicare Part A, B, home health, and hospice claims were included. ADL dependency was defined as needing help with bathing, eating, walking, dressing, toileting, or transferring. Potential predictors were demographics, International Classification of Diseases, Ninth Revision Clinical Modification diagnosis/procedure and durable medical equipment codes for frailty-associated conditions. Multivariable logistic regression was used to predict ADL dependency. Cox models estimated hazard ratios for death as a function of observed and predicted ADL dependency. RESULTS: Of 6391 respondents, 57% were female, 88% white, and 38% were ≥80. The prevalence of ADL dependency was 9.5%. Strong predictors of ADL dependency were charges for a home hospital bed (OR = 5.44, 95%CI = 3.28-9.03) and wheelchair (OR = 3.91, 95%CI = 2.78-5.51). The c-statistic of the final model was 0.845. Model-predicted ADL dependency of 20% or greater was associated with a hazard ratio for death of 3.19 (95%CI: 2.78, 3.68). CONCLUSIONS: An algorithm for predicting ADL dependency using health care claims was developed to measure some aspects of frailty. Accounting for variation in frailty among older adults could lead to more valid conclusions about treatment use, safety, and effectiveness.

Are Formal and Informal Home Mindfulness Practice Quantities Associated With Outcomes? Results From a Pilot Study of a Four-Week Mindfulness Intervention for Chronic Pain Management.

Background: The association between home mindfulness practice quantity in standard length mindfulness-based interventions (MBIs) and chronic pain outcomes is variable. Few studies focus on abbreviated MBIs (< 8 weeks) and distinguish between formal guided practices and informal practices in daily life. Objectives: To characterize home mindfulness practice and explore associations between home practice quantity and pre-to-post-outcome changes after an MBI for chronic pain. Methods: In this single-arm study, 21 adults with chronic pain (mean age = 54 years, 81% White, mean pain duration = 7 years) completed an MBI with four weekly group sessions. Pre and post self-report measures of pain intensity/interference, physical function, depression, anxiety, positive affect, sleep disturbance (all PROMIS measures), and pain acceptance, catastrophizing, perceived stress and mindfulness were completed, along with daily surveys of formal (mindfulness of breath, body scan) and informal (breathing space, mindfulness of daily activities) practice. Bivariate correlations and multivariable regression models were used to assess the association between days and minutes of practice and change in outcomes. Results: On average, formal practice was completed on 4.3 days per week and 13.5 minutes per day. Informal practice was completed on 3.5 days per week and 8.6 minutes per day. Formal practice was not significantly correlated with outcomes (Spearman's ρ = |.01|-|.32|), whereas informal practice was correlated with multiple outcomes (ρ = |.04|-|.66|). Number of days practiced informally was associated with improved pain interference, physical function, sleep disturbance, and catastrophizing (p's ≤ .05). Number of minutes practiced informally was associated with improved pain interference, anxiety, positive affect, and catastrophizing (p's ≤ .05). Conclusion: Informal home practice quantity, but not formal practice quantity, is associated with improved outcomes during an abbreviated MBI for chronic pain. For these MBIs, it is important to evaluate the distinct roles of formal and informal practice. ClinicalTrialsgov Registration: NCT03495856.

Collecting patient-reported outcome measures in the electronic health record: Lessons from the NIH pragmatic trials Collaboratory.

The NIH Pragmatic Trials Collaboratory supports the design and conduct of 27 embedded pragmatic clinical trials, and many of the studies collect patient reported outcome measures as primary or secondary outcomes. Study teams have encountered challenges in the collection of these measures, including challenges related to competing health care system priorities, clinician's buy-in for adoption of patient-reported outcome measures, low adoption and reach of technology in low resource settings, and lack of consensus and standardization of patient-reported outcome measure selection and administration in the electronic health record. In this article, we share case examples and lessons learned, and suggest that, when using patient-reported outcome measures for embedded pragmatic clinical trials, investigators must make important decisions about whether to use data collected from the participating health system's electronic health record, integrate externally collected patient-reported outcome data into the electronic health record, or collect these data in separate systems for their studies.

Low-n-6 and low-n-6 plus high-n-3 diets for use in clinical research.

Few trials have evaluated the metabolic effects and health outcomes of lowering dietary n-6 PUFA. The objectives of the present paper were (1) to report the methods employed to lower dietary n-6 PUFA, while either increasing or maintaining n-3 PUFA intake and (2) to validate our methods with 24 h recalls and erythrocyte fatty acid analyses. A total of sixty-seven subjects were randomised to either (1) an average-n-3 PUFA, low-n-6 PUFA (L6) intervention designed to lower linoleic acid (LA; #2·5% of energy (en%)) and arachidonic acid (#60 mg/d), while maintaining an average US intake of n-3 PUFA or (2) a high-n-3 PUFA, low-n-6 PUFA (H3-L6) intervention designed to lower n-6 LA, while increasing the n-3 PUFA a-linolenic acid (ALA; $1·5 en%) and EPA þ DHA ($1000 mg/d). Pre- and intraintervention nutrient intakes were estimated with six 24 h dietary recalls per subject. Both groups achieved the targeted reductions in dietary LA to #2·5 en% (median LA 2·45 (2·1, 3·1); P,0·001). Intakes of n-3 PUFA did not change for the L6 group. Target increases in n-3 ALA (median 1·6 en%, (1·3, 2·0), P,0·001) and EPA þ DHA (1482 mg, (374, 2558), P,0·001) were achieved in the H3-L6 group. Dietary changes were validated by corresponding changes in erythrocyte n-6 and n-3 fatty acid composition. Dietary LA can be lowered to #2·5 en%, with or without concurrent increases in dietary n-3 PUFA, in an outpatient clinical trial setting using this integrated diet method.

Missing data approaches in longitudinal studies of aging: A case example using the National Health and Aging Trends Study.

PURPOSE: Missing data is a key methodological consideration in longitudinal studies of aging. We described missing data challenges and potential methodological solutions using a case example describing five-year frailty state transitions in a cohort of older adults. METHODS: We used longitudinal data from the National Health and Aging Trends Study, a nationally-representative cohort of Medicare beneficiaries. We assessed the five components of the Fried frailty phenotype and classified frailty based on their number of components (robust: 0, prefrail: 1-2, frail: 3-5). One-, two-, and five-year frailty state transitions were defined as movements between frailty states or death. Missing frailty components were imputed using hot deck imputation. Inverse probability weights were used to account for potentially informative loss-to-follow-up. We conducted scenario analyses to test a range of assumptions related to missing data. RESULTS: Missing data were common for frailty components measured using physical assessments (walking speed, grip strength). At five years, 36% of individuals were lost-to-follow-up, differentially with respect to baseline frailty status. Assumptions for missing data mechanisms impacted inference regarding individuals improving or worsening in frailty. CONCLUSIONS: Missing data and loss-to-follow-up are common in longitudinal studies of aging. Robust epidemiologic methods can improve the rigor and interpretability of aging-related research.

Burnout and Wellness Strategies Used by Academic Physiatry Programs: An Analysis and Perspective From the AAP Chairs Council.

ABSTRACT: Physiatrists are at elevated risk of burnout, a work-related exhaustion syndrome resulting from chronic stress associated with emotionally draining work demands. The high reported rate of burnout in physical medicine and rehabilitation led the Association of Academic Physiatrists Chair Council to convene a workgroup to address burnout among academic physical medicine and rehabilitation physicians. The council recognizes that leaders of departments are accountable for all organizational stakeholders, including faculty, trainees, and staff. Department leaders are expected to understand and effectively manage the drivers of burnout among stakeholders. The workgroup identified several opportunities, including identifying and disseminating effective burnout mitigation across US academic medical center physical medicine and rehabilitation programs. As a result, in 2019, a work group conducted a survey of US academic physical medicine and rehabilitation program leaders to ascertain the use of strategies for reducing physician burnout. With the aim of identifying, educating, and advancing the development of effective interventions to address burnout among academic physical medicine and rehabilitation departments, the Association of Academic Physiatrists Chair Council advocates for increased education and utilization of effective strategies aimed at promoting physician well-being across organizational levels (national, organizational, work unit, and individual).

Associations between Plasma Lipid Mediators and Chronic Daily Headache Outcomes in Patients Randomized to a Low Linoleic Acid Diet with or without Added Omega-3 Fatty Acids.

A previous report showed that 12-week lowering of dietary omega-6 linoleic acid (LA) coupled with increased omega-3 polyunsaturated fatty acid (PUFA) intake (H3-L6 diet) reduced headache frequency and improved quality of life in patients with chronic daily headaches (CDHs) compared to dietary LA reduction alone (L6 diet). The trial also showed that targeted dietary manipulation alters PUFA-derived lipid mediators and endocannabinoids. However, several additional classes of lipid mediators associated with pain in preclinical models were not measured. The current secondary analysis investigated whether the clinical benefits of the H3-L6 diet were related to changes in plasma unesterified PUFA-derived lipid mediators known to be involved in nociception, including prostanoids. Lipid mediators were measured by ultra-high-pressure liquid chromatography coupled with tandem mass-spectrometry. Compared to baseline, dietary LA lowering with or without added omega-3 fatty acids did not alter unesterified n-6 PUFA-derived lipid mediators, although several species derived from LA, di-homo-gamma-linolenic acid, and arachidonic acid were positively associated with headache frequency and intensity, as well as mental health burden. Alpha-linolenic acid (ALA)-derived metabolites were also associated with increased headache frequency and intensity, although they did not change from the baseline in either dietary group. Compared to baseline, docosahexaenoic acid (DHA)-derived epoxides were more elevated in the H3-L6 group compared to the L6 group. Diet-induced elevations in plasma DHA-epoxides were associated with reduced headache frequency, better physical and mental health, and improved quality of life (p < 0.05). Prostanoids were not detected, except for PGF2-alpha, which was not associated with any outcomes. This study demonstrates that diet-induced changes in DHA-epoxides were associated with pain reduction in patients with chronic headaches, whereas n-6 PUFA and ALA metabolites were associated with nociception. Lipid mediator associations with mental health and quality of life paralleled pain management outcomes in this population. The findings point to a network of multiple diet-modifiable lipid mediator targets for pain management in individuals with CDHs.

Dietary fatty acids improve perceived sleep quality, stress, and health in migraine: a secondary analysis of a randomized controlled trial.

Background: Migraine is a prevalent disabling condition often associated with comorbid physical and psychological symptoms that contribute to impaired quality of life and disability. Studies suggest that increasing dietary omega-3 fatty acid is associated with headache reduction, but less is known about the effects on quality of life in migraine. Methods: After a 4-week run-in, 182 adults with 5-20 migraine days per month were randomized to one of the 3 arms for sixteen weeks. Dietary arms included: H3L6 (a high omega-3, low omega-6 diet), H3 (a high omega-3, an average omega-6 diet), or a control diet (average intakes of omega-3 and omega-6 fatty acids). Prespecified secondary endpoints included daily diary measures (stress perception, sleep quality, and perceived health), Patient-Reported Outcome Measurement Information System Version 1.0 ([PROMIS©) measures and the Migraine Disability Assessment (MIDAS). Analyses used linear mixed effects models to control for repeated measures. Results: The H3L6 diet was associated with significant improvements in stress perception [adjusted mean difference (aMD): -1.5 (95% confidence interval: -1.7 to -1.2)], sleep quality [aMD: 0.2 (95% CI:0.1-0.2)], and perceived health [aMD: 0.2 (0.2-0.3)] compared to the control. Similarly, the H3 diet was associated with significant improvements in stress perception [aMD: -0.8 (-1.1 to -0.5)], sleep quality [aMD: 0.2 (0.1, 0.3)], and perceived health [aMD: 0.3 (0.2, 0.3)] compared to the control. MIDAS scores improved substantially in the intervention groups compared with the control (H3L6 aMD: -11.8 [-25.1, 1.5] and H3 aMD: -10.7 [-24.0, 2.7]). Among the PROMIS-29 assessments, the biggest impact was on pain interference [H3L6 MD: -1.8 (-4.4, 0.7) and H3 aMD: -3.2 (-5.9, -0.5)] and pain intensity [H3L6 MD: -0.6 (-1.3, 0.1) and H3 aMD: -0.6 (-1.4, 0.1)]. Discussion: The diary measures, with their increased power, supported our hypothesis that symptoms associated with migraine attacks could be responsive to specific dietary fatty acid manipulations. Changes in the PROMIS© measures reflected improvements in non-headache pain as well as physical and psychological function, largely in the expected directions. These findings suggest that increasing omega-3 with or without decreasing omega-6 in the diet may represent a reasonable adjunctive approach to reducing symptoms associated with migraine attacks. Trial Registration: ClinicalTrials.gov NCT02012790.