Early Evidence of Chronic Obstructive Pulmonary Disease Obscured by Race-Specific Prediction Equations.

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES race-specific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD.

Use of the Spirometric "Fixed-Ratio" Underdiagnoses COPD in African-Americans in a Longitudinal Cohort Study.

BACKGROUND: COPD diagnosis is tightly linked to the fixed-ratio spirometry criteria of FEV1/FVC < 0.7. African-Americans are less often diagnosed with COPD. OBJECTIVE: Compare COPD diagnosis by fixed-ratio with findings and outcomes by race. DESIGN: Genetic Epidemiology of COPD (COPDGene) (2007-present), cross-sectional comparing non-Hispanic white (NHW) and African-American (AA) participants for COPD diagnosis, manifestations, and outcomes. SETTING: Multicenter, longitudinal US cohort study. PARTICIPANTS: Current or former smokers with ≥ 10-pack-year smoking history enrolled at 21 clinical centers including over-sampling of participants with known COPD and AA. Exclusions were pre-existing non-COPD lung disease, except for a history of asthma. MEASUREMENTS: Subject diagnosis by conventional criteria. Mortality, imaging, respiratory symptoms, function, and socioeconomic characteristics, including area deprivation index (ADI). Matched analysis (age, sex, and smoking status) of AA vs. NHW within participants without diagnosed COPD (GOLD 0; FEV1 ≥ 80% predicted and FEV1/FVC ≥ 0.7). RESULTS: Using the fixed ratio, 70% of AA (n = 3366) were classified as non-COPD, versus 49% of NHW (n = 6766). AA smokers were younger (55 vs. 62 years), more often current smoking (80% vs. 39%), with fewer pack-years but similar 12-year mortality. Density distribution plots for FEV1 and FVC raw spirometry values showed disproportionate reductions in FVC relative to FEV1 in AA that systematically led to higher ratios. The matched analysis demonstrated GOLD 0 AA had greater symptoms, worse DLCO, spirometry, BODE scores (1.03 vs 0.54, p < 0.0001), and greater deprivation than NHW. LIMITATIONS: Lack of an alternative diagnostic metric for comparison. CONCLUSIONS: The fixed-ratio spirometric criteria for COPD underdiagnosed potential COPD in AA participants when compared to broader diagnostic criteria. Disproportionate reductions in FVC relative to FEV1 leading to higher FEV1/FVC were identified in these participants and associated with deprivation. Broader diagnostic criteria for COPD are needed to identify the disease across all populations.

Circadian timing, melatonin and hippocampal volume in later-life adults.

Hippocampal atrophy is a prominent neurodegenerative feature of Alzheimer's disease and related dementias. Alterations in circadian rhythms can exacerbate cognitive aging and neurodegeneration. This study aimed to examine how dim light melatonin onset and melatonin levels are associated with hippocampal volume in cognitively healthy individuals. We studied data from 52 later-life adults (mean age ± SD = 70.0 ± 6.3 years). T1-weighted anatomical images from 3.0 T magnetic resonance imaging data were collected and processed using the BRAINSTools toolbox. Dim light melatonin onset was used to assess circadian timing. The area under the curve was calculated to quantify melatonin concentration levels 6 hr before bedtime, and 14-day wrist actigraphy data were used to assess habitual bedtime. Multiple linear regression modelling with hippocampal volume as the dependent variable was used to analyse the data adjusting for age and sex. The average dim light melatonin onset was 19:45 hours (SD = 84 min), and area under the curve of melatonin levels 6 hr before habitual bedtime was 38.4 pg ml-1 × hr (SD = 29.3). We found that later dim light melatonin onset time (b = 0.16, p = 0.005) and greater area under the curve of melatonin levels 6 hr before habitual bedtime (b = 0.05, p = 0.046) were associated with greater adjusted hippocampal volume. The time between dim light melatonin onset and the midpoint of sleep timing was not associated with hippocampal volume. The findings suggest that earlier circadian timing (dim light melatonin onset) and reduced melatonin may be associated with reduced hippocampal volume in older adults. Future research will help researchers utilize circadian rhythm information to delay brain aging.

Tobacco industry ownership of pharmaceutical companies: an international survey of people with respiratory disease.

The 2021 purchase of the respiratory pharmaceutical company Vectura by Phillip Morris International has been criticised by the public health and medical community, as a conflict of interest, with little input to date, from the patient community or the public. To address this gap, the COPD Foundation, along with global partners, surveyed 1196 people with chronic respiratory disease. 70% were bothered by a tobacco company making an inhaler to treat lung conditions and 48% reported that they would want to switch inhalers if they knew that a tobacco company made or sold their inhaler devices. Patients care about who makes the therapies used to treat their diseases.

Optimism is associated with respiratory symptoms and functional status in chronic obstructive pulmonary disease.

BACKGROUND: Optimism is the general belief that good things will occur in the future; optimism is modifiable by cognitive behavioral therapy (CBT). Previous studies have associated higher optimism with improved health outcomes and lower all-cause mortality. RESEARCH QUESTION: Investigate association between optimism and disease-related characteristics in chronic obstructive pulmonary disease (COPD). STUDY DESIGN AND METHODS: Current and former smokers with/without COPD and Preserved Ratio Impaired Spirometry (PRISm) from the 10-year follow-up visit for the Genetic Epidemiology of COPD (COPDGene) study were included. Optimism was assessed at the 10-year visit using the Life Orientation Test-Revised. Models of optimism as a predictor of lung function, COPD-associated phenotypes including exacerbations, and functional assessments, were adjusted for demographic confounders, smoking status, and comorbidities. RESULTS: Among 1967 subjects, higher optimism was significantly associated with older age, non-Hispanic white race, marital status, quitting smoking status, absence of COPD, and absence of depression. In multivariable analysis, higher optimism was independently associated with fewer prior exacerbations of COPD (coef = - 0.037, P < 0.001). Higher optimism was also related to better MMRC scores (coef = - 0.041, P < 0.001), CAT scores (coef = - 0.391, P < 0.001), SGRQ scores (coef = - 0.958, P < 0.001), BODE index (coef = - 0.059, P < 0.001), and longer 6-min walk distance (coef = 10.227, P < 0.001). After stratification by severity of COPD, these associations with optimism were still significant in all groups. No significant association was observed for cross-sectional FEV1 (%) or FVC (%) with optimism score. INTERPRETATION: Fewer exacerbations and less severe respiratory symptoms and higher functional capacity were associated with higher optimism, which may impact health outcomes in current and former smokers with and without COPD. Optimism is a modifiable trait and these results may further support a role for CBT to improve outcomes in COPD.

Symptoms of Anxiety, Burnout, and PTSD and the Mitigation Effect of Serologic Testing in Emergency Department Personnel During the COVID-19 Pandemic.

STUDY OBJECTIVE: Among a comprehensive range of frontline emergency department health care personnel, we assessed symptoms of anxiety and burnout, specific coronavirus disease 2019 (COVID-19) work-related stressors, and risk for post-traumatic stress disorder (PTSD). We also determined whether COVID-19 serologic testing of HCP decreased their self-reported anxiety. METHODS: In a prospective cohort study from May 13, 2020, to July 8, 2020, we used electronic surveys to capture participant self-reported symptoms before and after serologic testing for anti-SARS-CoV-2 immunoglobulin G antibodies. Participants were physicians, nurses, advanced practice providers, and nonclinical ED personnel at 20 geographically diverse United States EDs. We evaluated these domains: 1) the effects of the COVID-19 pandemic on overall stress and anxiety; 2) COVID-19-related work stressors; 3) burnout; and 4) PTSD risk (measured using the Primary Care-PTSD Screen for DSM-5, a 5-item screening instrument in which a score of ≥3 signifies high risk for PTSD). We also assessed perceptions of whether results of COVID-19 antibody testing decreased participants' self-reported anxiety. RESULTS: Of 1,606 participants, 100% and 88% responded to the baseline and follow-up surveys, respectively. At baseline, approximately half (46%) reported symptoms of emotional exhaustion and burnout from their work, and 308 (19.2%, 95% confidence interval [CI] 17.3% to 21.1%) respondents screened positive for increased PTSD risk. Female respondents were more likely than males to screen positive (odds ratio [OR] 2.03, 95% CI 1.49 to 2.78). Common concerns included exposing their family and the health of coworkers diagnosed with COVID-19. After receiving antibody test results, 54% (95% CI 51.8 to 56.7) somewhat agreed, agreed, or strongly agreed that knowledge of their immune status had decreased their anxiety. A positive serology result indicating prior SARS-CoV-2 infection was associated with a higher likelihood of reporting decreased anxiety (2.83, 95% CI 1.37 to 5.83). CONCLUSION: Symptoms of anxiety and burnout were prevalent across the spectrum of ED staff during the COVID-19 pandemic. One-fifth of ED personnel appeared to be at risk for PTSD. Increased provision of serologic testing may help to mitigate anxiety.

Reduced Attention in Former Smokers with and without COPD.

BACKGROUND: Attention difficulties are often reported by patients with chronic obstructive pulmonary disease (COPD); however, limited research exists using objective tests designed specifically to measure attention in this population. This study aimed to (1) identify specific attention deficits in COPD and (2) determine which demographic/clinical characteristics are associated with reduced attention. METHODS: Eighty-four former smokers (53 COPD, 31 no COPD) completed questionnaires, pulmonary function testing, and the Conner's Continuous Performance Test II (CPT-II). Participants with and without COPD were compared on CPT-II measures of inattention, impulsivity, and vigilance. CPT-II measures that differed significantly between the two groups were further examined using hierarchical regression modeling. Demographic/clinical characteristics were entered into models with attention as the dependent variable. RESULTS: Participants with COPD performed worse than those without COPD on CPT measures of inattention and impulsivity (i.e., detectability [discrimination of target from non-target stimuli], perseverations [reaction time under 100 ms], omissions [target stimuli response failures], and commissions [responses to non-target stimuli]). More severe COPD (measured by greater airflow limitation) was associated with poorer ability to detect targets vs. foils and perseverative responding after adjusting for age and other covariates in the model. CONCLUSION: Former smokers with COPD experience problems with attention that go beyond slowed processing speed, including aspects of inattention and impulsivity. Clinicians should be aware that greater airflow limitation and older age are associated with attention difficulties, as this may impact functioning.

The social environment and illness uncertainty in chronic obstructive pulmonary disease.

PURPOSE: Illness uncertainty is associated with worse outcomes in patients with chronic health conditions. Research on social factors associated with uncertainty has focused on the beneficial role of social support. The goal of this study was to develop a more nuanced understanding of the social factors that are associated with uncertainty. METHODS: Four hundred sixty-two individuals with alpha-1 antitrypsin deficiency (AATD)-associated chronic obstructive pulmonary disease (COPD) completed a mailed questionnaire. Measures of the social environment included general family functioning, perceived criticism from family members, whether the participant had family members with AATD or COPD, and participation in support groups. Uncertainty was measured using the Mishel Uncertainty in Illness Scale including subscales for ambiguity (uncertainty about physical cues and symptoms) and complexity (uncertainty about treatment and the medical system). Hierarchical regression was used to identify social correlates of ambiguity and complexity while adjusting for demographic and medical characteristics and psychological distress. RESULTS: Perceived criticism was associated with more complexity (b = 0.21, SE = 0.09, p = 0.015) and ambiguity (b = 0.40, SE = 0.12, p = 0.001). Having a family member with AATD or COPD was associated with more ambiguity (b = 3.28, SE = 1.00, p = 0.001). Participation in support groups was associated with less ambiguity. Individuals who attended three or more support groups in the prior year reported less ambiguity than individuals who had not attended any (b = -3.31, SE = 1.29, p = 0.010). CONCLUSIONS: The social environment is complex and encompasses more than social support. Multiple aspects of the social environment are associated with uncertainty, including perceived criticism, having a family member with a similar illness, and participation in support groups.

Association Between Improved Serum Fatty Acid Profiles and Cognitive Function During a Dietary Intervention Trial in Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Cognitive impairment is a common multiple sclerosis (MS)-related symptom that impacts quality of life (QOL). Diet interventions are shown to be beneficial in managing QOL, and the intake of essential fatty acids is linked with improved cognitive function. However, the effect of diets on serum fatty acid profiles and cognitive function is unknown. METHODS: A previous randomized, parallel-arm trial recruited participants with relapsing-remitting MS (N = 77). Study visits included 4 time points: run-in, baseline, 12 weeks, and 24 weeks. During the run-in phase, participants followed their usual diet and were then randomly assigned to either a modified paleolithic (Wahls) or a low saturated fat (Swank) diet at baseline. Assessments at study visits included cognitive function assessed by Symbol Digit Modalities Test-Oral (SDMT-O) and Perceived Deficits Questionnaire (PDQ), and serum fatty acids, including eicosapentaenoic (EPA), docosahexaenoic (DHA), and arachidonic (ARA) acids. RESULTS: Both groups had significant improvements in all serum fatty acids (P < .01), except for ARA, as well as SDMT-O at 24-weeks (P < .05), total PDQ at 12 and 24 weeks (P < .01) compared with baseline values. The 12-week changes in ω-3 (EPA + DHA) index and EPA serum fatty acids were associated with SDMT-O changes (P ≤ .05); however, the changes in fatty acid levels did not mediate the effect of the diets on SDMT-O or PDQ (P > .05). CONCLUSIONS: Both diets led to improvements in serum fatty acid profiles and cognitive function, with associations between the 12-week ω-3 (EPA + DHA) index and EPA changes with SDMT-O.

Effects of a Remote Multimodal Intervention Involving Diet, Walking Program, and Breathing Exercise on Quality of Life Among Newly Diagnosed People with Multiple Sclerosis: A Quasi-Experimental Non-Inferiority Pilot Study.

Background: Interventions involving diet, physical activity, and breathing exercises are shown to be beneficial in managing both fatigue and quality of life (QoL) related to MS; however, the impact of such interventions among people newly diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS) who decline disease-modifying therapies (DMTs) is unknown. Methods: A 12-month prospective quasi-experimental non-inferiority trial recruited people newly diagnosed with CIS or RRMS who voluntarily declined DMTs (health behavior group; HB, n = 29) or followed standard of care (SOC, n = 15). Participants in the HB group were remotely coached on the study diet, moderate-intensity walking, and breathing exercises. All participants completed questionnaires validated to assess MS symptoms, including perceived mental and physical QoL (MSQOL54); fatigue (Fatigue Severity Scale, FSS; and Modified Fatigue Impact Scale, MFIS); mood (Hospital Anxiety and Depression Scale, HADS); and cognitive function (Perceived Deficits Questionnaire, PDQ). Results: During the 12 months, the HB group experienced improvement in scores for mental QoL (MSQOL54 - Mental, 0.24, 95% CI 0.01, 0.47; p = 0.04), fatigue (Total MFIS, -7.26, 95% CI -13.3,-1.18; p = 0.02), and perceived cognitive function (Total PDQ, PDQ-Attention, PDQ-Promemory, and PDQ-Planning, p ≤ 0.03 for all). A between-group difference was observed only for PDQ-Planning (p = 0.048). Non-inferiority analysis revealed that the 12-month changes in means for the HB group were not worse than those for the SOC group with respect to fatigue (FSS, p = 0.02), mood (HDS-Anxiety, p = 0.02; HADS-Depression, p < 0.0001), physical QoL (MSQOL54 - Physical, p = 0.02), or cognitive dysfunction (Total PDQ, p = 0.01). Conclusion: The multimodal lifestyle intervention for individuals newly diagnosed with CIS or RRMS, who voluntarily decline DMTs, did not yield patient-reported outcomes worse than those observed in the SOC group regarding perceived mental quality of life, mood, fatigue, and cognitive function. Trial Registration: clinicaltrials.gov identifier: NCT04009005.

Examining the Effect of Genes on Depression as Mediated by Smoking and Modified by Sex.

Depression is heritable, differs by sex, and has environmental risk factors such as cigarette smoking. However, the effect of single nucleotide polymorphisms (SNPs) on depression through cigarette smoking and the role of sex is unclear. In order to examine the association of SNPs with depression and smoking in the UK Biobank with replication in the COPDGene study, we used counterfactual-based mediation analysis to test the indirect or mediated effect of SNPs on broad depression through the log of pack-years of cigarette smoking, adjusting for age, sex, current smoking status, and genetic ancestry (via principal components). In secondary analyses, we adjusted for age, sex, current smoking status, genetic ancestry (via principal components), income, education, and living status (urban vs. rural). In addition, we examined sex-stratified mediation models and sex-moderated mediation models. For both analyses, we adjusted for age, current smoking status, and genetic ancestry (via principal components). In the UK Biobank, rs6424532 [LOC105378800] had a statistically significant indirect effect on broad depression through the log of pack-years of cigarette smoking (p = 4.0 × 10-4) among all participants and a marginally significant indirect effect among females (p = 0.02) and males (p = 4.0 × 10-3). Moreover, rs10501696 [GRM5] had a marginally significant indirect effect on broad depression through the log of pack-years of cigarette smoking (p = 0.01) among all participants and a significant indirect effect among females (p = 2.2 × 10-3). In the secondary analyses, the sex-moderated indirect effect was marginally significant for rs10501696 [GRM5] on broad depression through the log of pack-years of cigarette smoking (p = 0.01). In the COPDGene study, the effect of an SNP (rs10501696) in GRM5 on depressive symptoms and medication was mediated by log of pack-years (p = 0.02); however, no SNPs had a sex-moderated mediated effect on depressive symptoms. In the UK Biobank, we found SNPs in two genes [LOC105378800, GRM5] with an indirect effect on broad depression through the log of pack-years of cigarette smoking. In addition, the indirect effect for GRM5 on broad depression through smoking may be moderated by sex. These results suggest that genetic regions associated with broad depression may be mediated by cigarette smoking and this relationship may be moderated by sex.

Availability and use of institutional support programs for emergency department healthcare personnel during the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic placed health care personnel (HCP) at risk for stress, anxiety, burnout, and post-traumatic stress disorder (PTSD). To address this, hospitals developed programs to mitigate risk. The objectives of the current study were to measure the availability and use of these programs in a cohort of academic emergency departments (EDs) in the United States early in the pandemic and identify factors associated with program use. METHODS: Cross-sectional survey of ED HCP in 21 academic EDs in 15 states between June and September 2020. Site investigators provided data on the availability of 28 programs grouped into 9 categories. Individual support programs included: financial, workload mitigation, individual COVID-19 testing, emotional (e.g., mental health hotline), and instrumental (e.g., childcare) Clinical work support programs included: COVID-19 team communication (e.g., debriefing critical incident), patient-family communication facilitation, patient services (e.g., social work, ethics consultation), and system-level exposure reduction. Participants provided corresponding data on whether they used the programs. We used generalized linear mixed models clustered on site to measure the association between demographic and facility characteristics and program use. RESULTS: We received 1,541 survey responses (96% response rate) from emergency physicians or advanced practice providers, nurses, and nonclinical staff. Program availability in each of the 9 categories was high (>95% of hospitals). Program use was variable, with clinical work support programs used more frequently (28-50% of eligible HCP across categories) than individual employee support programs (6-13% of eligible HCP across categories). Fifty-seven percent of respondents reported that the COVID-19 pandemic had affected their stress and anxiety, and 12% were at elevated risk for PTSD. Program use did not significantly differ for HCP who reported symptoms of anxiety and/or stress compared to those who did not. CONCLUSIONS: Early in the pandemic, support programs were widely available to ED HCP, but program use was low. Future work will focus on identifying barriers and facilitators to use and specific programs most likely to be effective during periods of highest occupational stress.

Obstructive sleep apnea: impact of hypoxemia on memory.

PURPOSE: Attempts to understand the causes of cognitive impairment in obstructive sleep apnea (OSA) are complicated by the overlap among clinical and demographic factors that may impact cognition. The goal of the current study was to isolate the contribution of hypoxemia to cognitive impairment in OSA. METHODS: Two groups of 20 patients with newly diagnosed OSA were compared. The groups differed on severity of hypoxemia but not other demographic (e.g., age, gender, education, estimated premorbid IQ) or clinical (e.g., sleep related respiratory disturbances, daytime sleepiness, depressive symptoms) variables. Participants completed polysonmography and cognitive assessment. RESULTS: We compared patients with high and low hypoxemia on measures of memory, attention, executive functioning, and motor coordination using independent sample t-tests. The high hypoxemia group performed significantly better on immediate recall (Hopkins Verbal Learning Test - Revised; t = -2.50, p < 0.02) than the low hypoxemia group. No group differences were observed on other neuropsychological measures. CONCLUSIONS: This study is one of the first to compare the cognitive performance of patients with high and low hypoxemia after controlling for demographic factors and aspects of OSA severity that could confound the relationship. In our carefully matched sample, we observed an unexpected advantage of higher hypoxemia on memory. These preliminary findings are discussed in the context of basic science literature on the protective effects of adaptation to intermittent hypoxemia. Our data suggest that the association between hypoxemia and cognition may not straightforward. Future research targeting the effects of hypoxemia on cognition controlling for other clinical factors in large groups of patients with OSA will be important.

Cognitive function and inhaler technique following recovery from exacerbations of COPD.

Cognitive impairment is highly prevalent in COPD outpatients during the post-exacerbation recovery period and is associated with poor inhaler technique https://bit.ly/3XkCvCv.

Patient Experiences with a Tertiary Care Post-COVID-19 Clinic.

Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC) is a complex condition with multisystem involvement. We assessed patients' experience with a PASC clinic established at University of Iowa in June 2020. A survey was electronically mailed in June 2021 asking about (1) symptoms and their impact on functional domains using the Patient-Reported Outcomes Measurement Information System (PROMIS) measures (Global Health and Cognitive Function Abilities) (2) satisfaction with clinic services, referrals, barriers to care, and recommended support resources. Survey completion rate was 35% (97/277). Majority were women (67%), Caucasian (93%), and were not hospitalized (76%) during acute COVID-19. As many as 50% reported wait time between 1 and 3 months, 40% traveled >1 h for an appointment and referred to various subspecialities. Participants reported high symptom burden-fatigue (77%), "brain fog" (73%), exercise intolerance (73%), anxiety (63%), sleep difficulties (56%) and depression (44%). On PROMIS measures, some patients scored significantly low (≥1.5 SD below mean) in physical (22.7%), mental (15.9%), and cognitive (17.6%) domains. Approximately 61% to 93% of participants were satisfied with clinical services. Qualitative analysis added insight to their experience with healthcare. Participants suggested potential strategies for optimizing recovery, including continuity of care, a co-located multispecialty clinic, and receiving timely information from emerging research. Participants appreciated that physicians validated their symptoms and provided continuity of care and access to specialists.

Association of serum homocysteine, folate, and vitamin B12 and mood following the Swank and Wahls elimination dietary interventions in relapsing-remitting multiple sclerosis: Secondary analysis of the WAVES trial.

BACKGROUND: Depression and anxiety are common psychiatric comorbidities among people with multiple sclerosis (MS). Emerging data suggest abnormal serum homocysteine, vitamin B12, and folate levels in people with MS, which are related to a range of neurological disorders, including mood and mental illnesses. Evidence suggests that dietary interventions could affect mood disorders via several pathways. This study aimed to evaluate the impact of the low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets, along with a supplement regimen, on mood as assessed by Hospital Anxiety and Depression Scale (HADS), and Mental Health Inventory (MHI). The secondary objective was to identify changes in serum levels of homocysteine, folate, and vitamin B12 and the association and mediation effects between their changes and HADS and MHI scores and their subscales among people with relapsing-remitting MS (RRMS). METHODS: In a previously conducted randomized parallel-arm trial, participants with RRMS (n = 77) were randomly allocated to either the Swank or Wahls diets at baseline and followed for 24 weeks. Blood was drawn at four study visits spaced 12 weeks apart: (1) run-in, (2) baseline, (3) 12 weeks, and (4) 24 weeks. Serum vitamin B12, folate, and homocysteine were analyzed. HADS and MHI questionnaires were also completed by participants at the four study visits to assess symptoms of depression and anxiety, behavioral control and positive affect respectively. RESULTS: Significant improvement in severity of depression (HADS-D) and anxiety (HADS-A) symptoms, MHI total, and MHI subscores were seen at 12 and 24 weeks in each diet group. Further, a significant within-group reduction in serum homocysteine and a significant increase in serum vitamin B12 level were observed in both groups at 12 and 24 weeks compared to corresponding baseline values (p ≤ 0.05 for all). All participants exceeded the analytical maximum threshold for folate of 20 nmol/L at 12 and 24 weeks. Changes in serum levels of homocysteine and vitamin B12 were not associated with and did not mediate changes in HADS depression, anxiety, MHI total and four subscales scores (p > 0.05). CONCLUSION: Participants on both Swank and Wahls dietary interventions, including folate and vitamin B12 supplements, showed significant improvement in mood. However, the favorable effects of both diets on mood were not associated with or mediated by the effect of the diets on serum levels of homocysteine, folate, and vitamin B12 (p > 0.05).

Presence of symptoms 6 weeks after COVID-19 among vaccinated and unvaccinated US healthcare personnel: a prospective cohort study.

OBJECTIVES: Although COVID-19 vaccines offer protection against infection and severe disease, there is limited information on the effect of vaccination on prolonged symptoms following COVID-19. Our objective was to determine differences in prevalence of prolonged symptoms 6 weeks after onset of COVID-19 among healthcare personnel (HCP) by vaccination status, and to assess differences in timing of return to work. DESIGN: Cohort analysis of HCP with COVID-19 enrolled in a multicentre vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset. SETTING: Health systems in 12 US states. PARTICIPANTS: HCP participating in a vaccine effectiveness study were eligible for inclusion if they had laboratory-confirmed symptomatic SARS-CoV-2 with mRNA vaccination (symptom onset ≥14 days after two doses) or no prior vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey to assess symptoms reported 6 weeks after illness onset. EXPOSURES: Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine. MAIN OUTCOME MEASURES: Prevalence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work. RESULTS: Among 419 HCP with COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants compared with unvaccinated participants (60.6% vs 79.1%; adjusted risk ratio 0.70, 95% CI 0.58 to 0.84). Following their illness, vaccinated HCP returned to work a median 2.0 days (95% CI 1.0 to 3.0) sooner than unvaccinated HCP (adjusted HR 1.37, 95% CI 1.04 to 1.79). CONCLUSIONS: Receipt of two doses of a COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased prevalence of COVID-like symptoms at 6 weeks and earlier return to work.

Factors associated with the decision to receive bivalent COVID-19 booster vaccination among health care personnel.

COVID-19 vaccination is effective at reducing SARS-CoV-2 complications, but uptake has been low. Our objective in this study was to compare the importance of factors reported to influence the decision to receive a bivalent COVID-19 booster vaccine among health care personnel (HCP) tested for SARS-CoV-2 between October 2022 and April 2023 in a 20-hospital vaccine effectiveness study in the United States (n = 1656). Compared with those who had not received the booster, the factors most likely to be reported to be important were concerns about contracting COVID-19 (84.0% of those who had received the bivalent booster vs. 47.5% of those who had not, difference 36.6% points (PP), 95% confidence interval [CI] 32.1 to 41.1%), spreading infection to family members (89.2% vs. 62.8%, difference 26.3 PP, 95% CI 22.3 to 30.4%), and spreading infection to colleagues at work (85.5% vs. 59.4%, difference 26.1 PP, 95% CI 21.7 to 30.5%). HCP who had received the booster more frequently cited the primary literature (61.7% vs. 31.8%, difference 29.9 PP, 95% CI 24.6 to 35.2%) and employer recommendations (48.3% vs. 29.8%, difference 18.5 PP, 95% CI 13.2 to 23.9%) as influencing their decision. This analysis provides insight into factors for targeting future vaccine messaging.

Diet-induced changes in functional disability are mediated by fatigue in relapsing-remitting multiple sclerosis: A secondary analysis of the WAVES randomized parallel-arm trial.

Background: People with multiple sclerosis (MS) often report dietary modifications; however, evidence on functional outcomes remains sparse. Objective: Evaluate the impact of the low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets on functional disability among people with relapsing-remitting MS. Methods: Baseline-referenced MS functional composite (MSFC) scores were calculated from nine-hole peg-test (NHPT), timed 25-foot walk, and oral symbol digit modalities test (SDMT-O) collected at four study visits: (a) run-in, (b) baseline, (c) 12 weeks, and (d) 24 weeks. Participants were observed at run-in and then randomized at baseline to either the Swank (n = 44) or Wahls (n = 43) diets. Results: Among the Swank group, MSFC scores significantly increased from -0.13 ± 0.14 at baseline to 0.10 ± 0.11 at 12 weeks (p = 0.04) and 0.14 ± 0.11 at 24 weeks (p = 0.02). Among the Wahls group, no change in MSFC scores was observed at 12 weeks from 0.10 ± 0.11 at baseline but increased to 0.28 ± 0.13 at 24 weeks (p = 0.002). In both groups, NHPT and SDMT-O z-scores increased at 24 weeks. Changes in MSFC and NHPT were mediated by fatigue. Discussion: Both diets reduced functional disability as mediated by fatigue. Trial Registration: Clinicaltrials.gov Identifier: NCT02914964.