Mixed-effects Linear Regression Models Research Articles

Serologic responses to the MVA-based JYNNEOS mpox vaccine in a cohort of participants from the District of Columbia (D.C.)

We assessed early antibody responses after two doses of JYNNEOS (IMVANEX) mpox vaccine in the District of Columbia (D.C.) in persons at high risk for mpox without characteristic lesions or rash. Participants with PCR mpox negative specimens (oral swab, blood, and/or rectal swab) on the day of receipt of the first vaccine dose and who provided a baseline (day 0) serum sample and at least one serum sample at ∼28, ∼42–56 days, or 180 days post vaccination were included in this analysis. Orthopoxvirus (OPXV)-specific IgG and IgM ELISAs and neutralizing antibody titers were performed, and longitudinal serologic responses were examined. Based on participants’ IgG and IgM antibody levels at baseline, they were categorized as naïve or non-naïve. Linear mixed effects regression models were conducted to determine if IgG antibody response over time varied by age, sex, HIV status, and route of administration for both naïve and non-naïve participants. Among both naïve and non-naïve participants IgG seropositivity rates increased until day 42–56, with 89.4 % of naïve and 92.1 % of non-naïve participants having detectable IgG antibodies. The proportion of naive participants with detectable IgG antibodies declined by day 180 (67.7 %) but remained high among non-naïve participants (94.4 %). Neutralizing antibody titers displayed a similar pattern, increasing initially post vaccination but declining by day 180 among naïve participants. There were no significant serologic response differences by age, sex, or HIV status. Serologic response did vary by route of vaccine administration, with those receiving a combination of intradermal and subcutaneous doses displaying significantly higher IgG values than those receiving both doses intradermally. These analyses provide initial insights into the immunogenicity of a two-dose JYNNEOS PEP regimen in individuals at high risk of mpox exposure in the United States.

Primary Care Organizational Support for Nurse Practitioner Practice and Emotional Health Care Delivery.

Nurse practitioners (NPs) are key to delivery of primary care services. However, poor organizational support for independent NP practice, such as lack of access to clinic resources, may lead to prioritizing patient physical health over emotional health. We investigated the relationship between organizational support for independent NP practice and emotional health care delivery. This was a secondary analysis of cross-sectional survey data collected from 397 NPs in 2017. We measured organizational support for independent NP practice using the independent practice and support subscale of the NP Primary Care Organizational Climate Questionnaire. Emotional health care delivery was measured by asking NPs how frequently they addressed emotional concerns of patients. We utilized multilevel mixed effects linear regression models, adjusting for NP and practice covariates. Controlling for NP age, gender, marital status, race, and ethnicity, along with practice setting and size, as the independent practice and support score increased, NPs reported addressing emotional concerns of patients more frequently (beta = 0.34, 95% confidence interval = 0.02-0.66, P = 0.04). This indicates that as organizations provided more support for independent NP practice, NPs were able to more frequently address emotional concerns of patients. Organizational support for independent NP practice is associated with addressing emotional concerns of patients. To support NP practice, primary care organizations should ensure that NPs manage patients independently and have access to ancillary staff and support for care management.

Psychological distress over 12 months post-diagnosis in an early inflammatory arthritis cohort.

People with inflammatory arthritis (IA) experience worsened mental wellbeing alongside disease progression. Using the National Early Inflammatory Arthritis Audit (NEIAA), we assessed trends in psychological distress during 12-months following IA diagnosis, mapping these against clinical outcomes to identify associations. This is a prospective study of people recruited to NEIAA receiving an IA diagnosis and completing the baseline patient survey. Patient reported outcomes (PROs) at baseline, 3-months and 12-months were collected, including psychological distress (assessed using Patient Health Questionnaire Anxiety and Depression Screener (PHQ4ADS)). Mixed effects linear regression models estimated associations between predictor variables with psychological distress at baseline and over time. Of 6,873 eligible patients, 3,451 (50.2%) showed psychological distress at baseline. Of those completing follow-ups, 30.0% and 24.1% were distressed at 3-months and 12-months, respectively. Higher psychological distress at diagnosis was more commonly reported by younger, female, and non-white patients. Clinical factors, including higher counts of comorbidities, prior depression, and higher disease activity at diagnosis were associated with higher distress. Higher distress at baseline was associated with poorer outcomes over time in quality of life, disability, work performance, disease activity, as well as reduced likelihood of achieving good treatment response by EULAR criteria. Half of patients with IA show significant mental health comorbidity at presentation, which associated with worse disease outcomes and quality of life. Screening for anxiety and depression should be a universal standard, and access to effective mood therapies alongside arthritis treatments is essential. Strategies should be culturally valid and consider multi-morbidities.

Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birthcohortanalysis, aimed to determine if repeated exposure to anticholinergic medicationswas associated with greater decline, and whether decline was reversed with medication reduction. From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified bythe Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantifiedby theWord Learning Test [WLT], and processing speed quantified by theTimed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms. Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference - 2.34, 95% confidence interval [CI] - 3.51 to - 1.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure - 0.90, 95% CI - 1.63 to - 0.17; mean difference with lagged exposure - 1.53, 95% CI - 2.43 to - 0.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to - 0.71; mean difference with lagged exposure - 2.23, 95% CI - 3.33 to - 1.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference - 13.14, 95% CI - 19.04 to - 7.23; p<0.01). Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.

Comparison of nursing staffing ratio in selected safety net and non-safety net hospitals in the United States

Comparison of nursing staffing ratio in selected safety net and non-safety net hospitals in the United States

Occurrence and characteristics of suicidal ideation in psychiatrically healthy individuals based on ecological momentary assessment.

Decedents with no known mental disorder comprise 5-40% of suicides, suggesting that suicide ideation (SI) and behavior may occur in the psychiatrically healthy with important implications for suicide risk screening. Healthy Volunteers (HV) and patients with Major Depressive Disorder (MDD) provided 7 days of Ecological Momentary Assessment (EMA) data about SI and stressors. Longitudinal mixed effects logistic regression models compared HV and patient SI and stressors. Mixed effects linear regression models compared HVs' and patients' SI score change from the previous epoch's SI score when each stressor occurred. HVs (n = 42) reported less frequent (p < 0.001) and less intense SI (p < 0.003) than patients (n = 80), yet did endorse SI and/or SI-related items in 44% of EMA epochs, endorsing SI items in 25% of epochs with non-zero SI scores. For 7 of 8 stressors, patients reported stressors more often than HVs (all p < 0.001) responding to them with increased SI (0.0001 < p < 0.0472). HVs were relatively resilient to stressors, reporting SI increases only in response to neglect (p < 0.0147). Although SI and SAs are documented among psychiatrically healthy individuals, scientific attention to these observations has been scant. Real-time SI measurement showed that HVs' SI was less pronounced than MDD patients', but was endorsed, nonetheless. Patients were more likely to report stressors than HVs, perhaps due to greater sensitivity to the environment, and reported SI in response to stressors, which was less common in HVs. Both MDD patients and HVs most often manifested passive SI (viz, "decreased wish to live"). However, passive SI (viz, "desire for death"), may predict suicide, even absent SI per se (thinking about killing yourself). This study validates the utility of real-time SI assessment, showing that HVs endorse SI items in 11% of epochs, which implies that suicide risk screening focused on those with mental disorders may be too narrow an approach.

Acute Hyperglycemia Induced by Hyperglycemic Clamp Affects Plasma Amyloid-β in Type 2 Diabetes.

Individuals with type 2 diabetes (T2D) have an increased risk of cognitive symptoms and Alzheimer's disease (AD). Mis-metabolism with aggregation of amyloid-β peptides (Aβ) play a key role in AD pathophysiology. Therefore, human studies on Aβ metabolism and T2D are warranted. The objective of this study was to examine whether acute hyperglycemia affects plasma Aβ 1-40 and Aβ 1-42 concentrations in individuals with T2D and matched controls. Ten participants with T2D and 11 controls (median age, 69 years; range, 66-72 years) underwent hyperglycemic clamp and placebo clamp (saline infusion) in a randomized order, each lasting 4 hours. Aβ 1-40, Aβ 1-42, and insulin-degrading enzyme (IDE) plasma concentrations were measured in blood samples taken at 0 and 4 hours of each clamp. Linear mixed-effect regression models were used to evaluate the 4-hour changes in Aβ 1-40 and Aβ 1-42 concentrations, adjusting for body mass index, estimated glomerular filtration rate, and 4-hour change in insulin concentration. At baseline, Aβ 1-40 and Aβ 1-42 concentrations did not differ between the two groups. During the hyperglycemic clamp, Aβ decreased in the control group, compared to the placebo clamp (Aβ 1-40: p = 0.034, Aβ 1-42: p = 0.020), IDE increased (p = 0.016) during the hyperglycemic clamp, whereas no significant changes in either Aβ or IDE was noted in the T2D group. Clamp-induced hyperglycemia was associated with increased IDE levels and enhanced Aβ 40 and Aβ 42 clearance in controls, but not in individuals with T2D. We hypothesize that insulin-degrading enzyme was inhibited during hyperglycemic conditions in people with T2D.

Smaller subcortical volume relates to greater weight gain in girls with initially healthy weight.

Among 3614 youth who were 9 to 12 years old and initially did not have overweight or obesity (12% [n = 385] developed overweight or obesity), we examined the natural progression of weight gain and brain structure development during a 2-year period with a high risk for obesity (e.g., pre- and early adolescence) to determine the following: 1) whether variation in maturational trajectories of the brain regions contributes to weight gain; and/or 2) whether weight gain contributes to altered brain development. Data were gathered from the Adolescent Brain Cognitive Development (ABCD) Study. Linear mixed-effects regression models controlled for puberty, caregiver education, handedness, and intracranial volume (random effects: magnetic resonance scanner [MRI] scanner and participant). Because pubertal development occurs earlier in girls, analyses were stratified by sex. For girls, but not boys, independent of puberty, greater increases in BMI were driven by smaller volumes over time in the bilateral accumbens, amygdala, hippocampus, and thalamus, right caudate and ventral diencephalon, and left pallidum (all p < 0.05). The results suggest a potential phenotype for identifying obesity risk because underlying differences among regions involved in food intake were related to greater weight gain in girls, but not in boys. Importantly, 2 years of weight gain may not be sufficient to alter brain development, highlighting early puberty as a critical time to prevent negative neurological outcomes.

Abstract PO4-12-08: Changes in peripheral immune cell composition in women who do and do not develop breast cancer

Abstract Background: Breast cancer survivors have higher age-specific rates of hypertension and other chronic diseases than women without a history of breast cancer. We and others have shown that alterations to the immune system are associated with risk of these conditions in the general population, leading to the hypothesis that the increased chronic disease risk in breast cancer survivors may be driven, in part, by lasting changes in immunity. Peripheral immune cell composition appears to become altered years before a breast cancer diagnosis, but little is currently known about the influence of different breast cancer treatments on subsequent changes to leukocyte composition and the persistence of these associations over time. Methods: Among 410 women enrolled in the Sister Study, paired blood samples collected an average of 7.6 years apart were analyzed for DNA methylation (DNAm). Deconvolution methods were applied to these DNAm data to estimate circulating percentages of 12 leukocyte subsets. Approximately half the women sampled were diagnosed and treated for breast cancer between the blood draws (n= 185) whereas the other half remained breast cancer-free (n= 225). Breast tumor characteristics and treatment information were abstracted from medical records. Mixed-effect linear regression models were used to estimate changes in leukocyte composition over time comparing women with breast cancer to those who remained breast cancer-free. A case-only analysis of breast cancer survivors was performed to examine the persistence of changes over time and to explore whether changes in leukocyte composition were associated with the types of therapies received (endocrine therapy, radiation therapy, chemotherapy). All models were adjusted for age and self-reported race. In the treatment analysis, because tumor characteristics can guide clinical decisions, tumor estrogen receptor status and stage at diagnosis were additionally included as model covariates. Results: At baseline, women who developed breast cancer between the blood draws had lower mean circulating percentages of CD8+ cytotoxic T cells than women who remained breast cancer-free (3.8% vs 4.6%; P-diff= 0.04). After accounting for differences in leukocyte composition at baseline, compared to women who remained breast cancer-free, women diagnosed and treated for breast cancer between the blood draws had decreases in total circulating CD4+ helper T cell percentage (adjusted mean difference [β]= -1.50, 95% CI: -2.56, -0.44, P= 0.006) and alterations to both naïve and memory B cell percentages (naïve B cells, β= 0.46, 95% CI: 0.17, 0.75, P= 0.002; memory B cells, β= -0.22, 95% CI: -0.34, -0.09, P= 0.001). Although associations did not vary by tumor characteristics or participant race, the changes in leukocyte composition appeared to persist over time as changes were not associated with time since diagnosis. In the case-only analysis of different breast cancer therapies, radiation was associated with decreases in CD4+ T cells (β= -2.56, 95% CI: -4.26, -0.88, P= 0.003) and chemotherapy was associated with increases in B cells (β= 0.62, 95% CI: 0.07, 1.16, P= 0.03). Surgery and endocrine therapy were not meaningfully associated with changes in leukocyte composition. Conclusions: Breast cancer survivors have lasting changes in peripheral leukocyte composition that may be related to the types of treatments received. These findings add to our understanding of the biological changes that underlie the long-term health of breast cancer survivors. Citation Format: Jacob Kresovich, Katie O'Brien, Zongli Xu, Clarice Weinberg, Dale Sandler, Jack Taylor. Changes in peripheral immune cell composition in women who do and do not develop breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-08.

Changes in Anti-OV-16 IgG4 Responses to Onchocerciasis after Elimination of Transmission in the Central Endemic Zone of Guatemala.

Current WHO guidelines for onchocerciasis elimination provide requirements for stopping mass drug administration of ivermectin and the verification of elimination of transmission. These guidelines also recommend post-elimination surveillance (PES) based on entomological surveys. Serological markers in humans could complement entomological PES once the longevity of anti-OV-16 antibody responses is better understood. In 2014-2015 we evaluated ELISA anti-OV-16 IgG4 antibody persistence among previously seropositive people from the central endemic zone of Guatemala. The country stopped all onchocerciasis program interventions in 2012 and was verified by WHO as having eliminated transmission of onchocerciasis in 2016. A total of 246 participants with prior OV-16 ELISA results from 2003, 2006, 2007, or 2009 were enrolled in a follow-up study. Of these, 77 people were previously OV-16 seropositive and 169 were previously seronegative. By 2014 and 2015, 56 (72.7%) previously seropositive individuals had sero-reverted, whereas all previous negatives remained seronegative. The progression of antibody responses over time was estimated using a mixed-effects linear regression model, using data from seropositive participants who had sero-reverted. The temporal variation showed a mean activity unit decay of 0.20 per year (95% credible interval [CrI]: 0.17, 0.23), corresponding to an estimated antibody response half-life of 3.3 years (95% CrI: 2.7, 4.1). These findings indicate that the majority of seropositive people will sero-revert over time.

Mycobacterium bovis vaccination and subsequent experimental infection outcomes are associated with changes in vitamin D status in dairy calves.

Investigations into the role of vitamin D (vitD) in the immune response of cattle are limited. The objectives of this study were therefore to investigate the association between circulating vitD concentration, TB vaccination and Mycobacterium bovis (M. bovis) infection outcomes in 24 dairy calves (<8 weeks old) which were housed throughout and fed a bodyweight-based allowance. The study design incorporated 2 phases: vaccination (experimental wk 0–52) and experimental infection phase (wk 52–65). Vaccinated calves (n = 12) received a subcutaneous injection of a live-attenuated TB strain at wk 0, whereas unvaccinated ones (n = 12) were injected with saline. All animals were infected with 7,600 cfu of M. bovis 52 weeks post-vaccination, and lung and lymph nodes tissues were assessed for pathology following euthanasia after wk 65. Blood samples were taken throughout wk 0–65. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured using a commercial ELISA. A mixed-effects linear regression model revealed significantly higher 25(OH)D concentrations in the vaccinates post-infection (wk 65) compared with the non-vaccinates. Linear regression analysis between 25(OH)D concentration and the level of M. bovis-driven pathology revealed a negative linear relationship i.e., higher concentrations were associated with lower pathology scores, irrespective of vaccination status. No correlation was detected between interferon-γ cytokine production and vitD concentration. Overall, the results support a significant role for vitD in the development of effective immunity of cattle against M. bovis. Gaining insight into the interaction between TB vaccination, M. bovis infection and vitD could potentially guide the optimization of vaccination protocols and future TB control strategies.

Adherence and acceptability of multiple micronutrient supplementation during pregnancy: Study protocol for a cluster-randomized non-inferiority trial in Cambodia

BackgroundIron and folic acid (IFA) supplements are currently provided to Cambodian women during pregnancy. However, recent research has found benefits of a multiple micronutrient supplement (MMS) over just IFA alone on several outcomes of perinatal and infant health. The Ministry of Health in Cambodia has proposed a transition from IFA to MMS but to effectively guide this transition requires implementation research on the acceptability and adherence to MMS (over IFA).MethodsThis non-inferiority trial aims to assess the adherence and acceptability of IFA (60 mg elemental iron and 400 μg folic acid) compared to MMS (standard UNIMMAP formulation including 15 micronutrients) during antenatal care in Cambodia. A prospective cohort of 1545 pregnant women will be assigned to one of three trial arms: (1) IFA for 90 days [IFA-90]; (2) MMS for 180 days with two distributions of 90-count tablet bottles [MMS-90]; or (3) MMS for 180 days with one 180-count tablet bottle [MMS-180]. Each arm will enroll 515 women across 48 health centers (clusters) in Kampong Thom Province in Cambodia. The primary outcome is the non-inferiority of adherence rates of MMS-180 compared to IFA-90, as assessed by tablet counts. Mixed-effects logistic and linear regression models will be used to estimate the difference in the adherence rate between the two groups, with an ‘a priori’ determined non-inferiority margin of 15%. Acceptability of MMS and IFA will be measured using a quantitative survey conducted with enrolled pregnant women at 30-day, 90-day, and 180-day time-points. DiscussionFindings from this study will guide an effective and feasible MMS scale-up strategy for Cambodia. Additionally, the findings will be shared globally with other stakeholders planning to scale up MMS in other countries.Trial registrationNCT05867836 (ClinicalTrials.gov, registered May 18, 2023).

Preliminary Impact of Group-Based Interventions on Stigma and the Mental Health of Caregivers of Adolescents Living with HIV in Uganda.

This study examined the preliminary impact of group-cognitive behavioral therapy (G-CBT) and a family-strengthening intervention delivered via multiple family groups (MFG-FS) on HIV stigma, parenting stress, and the mental health of caregivers of adolescents living with HIV. We analyzed data from the Suubi4Stigma study (2020-2022), a two-year pilot randomized clinical trial for adolescents and their caregivers (N = 89 dyads), recruited from nine health clinics in Uganda. Adolescent-caregiver dyads were randomized to three intervention conditions delivered over three months, with data collected at baseline, three and six-months follow-up. We fitted mixed-effects linear regression models to test the effect of the interventions on caregiver outcomes over time. At six months, caregivers randomized to the MFG-FS condition reported lower levels of stigma by association (mean difference = -1.45, 95% CI = -2.52 - -0.38, p = 0.008), and stigma and discrimination attitudes (mean difference = -3.84, 95% CI = -4.63 - -3.05, p < 0.001), compared to Usual care condition. In addition, caregivers of adolescents randomized to the G-CBT condition reported lower levels of stigma and discrimination attitudes at three months (mean difference = -5.18, 95% CI = -9.13 - -1.22, p = 0.010), and at six months (mean difference = -6.70, 95% CI = -9.28 - -4.12, p < 0.001). Caregiver mental health and parenting stress significantly reduced over time regardless of intervention condition. Findings point to the importance of incorporating stigma reduction components within psychosocial interventions targeting adolescents and families impacted by HIV.

Electrogenic transport of amino acids and glucose differs between jejunum and ileum of female and castrated male finishing pigs

It has been shown that the jejunum represents the most important site for the nutrient’s absorption in several species. However, in pigs, this information seems to be controversial and limited information are available about differences in intestinal physiology between female and castrated male pigs. The trans-epithelial electrical resistance (TEER) and the active uptake of L-glutamate (L-Glu), L-arginine (L-Arg), L-methionine (L-Met) and D-glucose (D-Glu) in the jejunum and ileum of female (n = 5) and castrated male (n = 7) pigs fed a protein-restricted grower and finisher diet (128 and 112 g of crude protein/kg dry matter) were investigated. The intestine segments were collected at slaughter and mounted in Ussing chambers. Results were further investigated by protein expression analysis of the D-Glu transporter Sodium-dependent Glucose Transporter 1 (SGLT1) and using serum creatinine, non-esterified fatty acids (NEFAs) and serum glucose concentrations measurements as indicators of muscle mass deposition and metabolic status of the animals. A linear mixed-effects regression (Lme4) model was used for data analysis. Independent of sex, the uptake of both L-Met and D-Glu was higher (p < 0.001) in the ileum than in the jejunum (2.1- and 3.6-fold increases, respectively). The L-Arg uptake was higher (p = 0.001) in females compared to castrates (1.9-fold increase). No significant differences were observed between the segments in the SGLT1 protein expression, regardless of sex. Serum measurements were also not significantly different between the female and castrates. This study suggests that the ileum has an important role in the active uptake of amino acids and D-Glu uptake and differences exist between female and castrated finishing pigs.

P062 Trust performance in managing inflammatory arthritis over time in England and Wales: a latent class analysis approach

Abstract Background/Aims To evaluate trust-level performance in time to initiation of disease-modifying antirheumatic drug (DMARD) therapy in patients with early inflammatory arthritis (EIA), with identification of change in performance trajectories over time and investigation of trust characteristics associated with this change. Methods We included 130 trusts from the UK contributing to the National Early Inflammatory Arthritis Audit (NEIAA) from 2018 to 2020. The primary outcome was days from referral to initiation of DMARD therapy in patients with EIA. Latent class growth mixture models were applied to identify distinct groups of trusts with similar trajectories of performance change over time. We used mixed-effects linear and multinomial logistic regression models to evaluate the association between delay in treatment and trust-level characteristics. Results The mean (SD) time to DMARD initiation was 53 (18) days, with an average 0.3-day decrease with each month over time. Four latent trajectories were identified in our cohort, with over 77% of individual trusts showing ongoing improvements in decreasing treatment waiting times. Prior to separating by latent class, time to DMARD initiation was shorter in trusts with higher rheumatology staffing, a local EIA treatment pathway and those with access to musculoskeletal ultrasound. Trusts with more nurses in the rheumatology department were less likely to be in the worse performance group (OR = 0.69 [95%CI 0.49, 0.93]). Conclusion In this cohort study, we observed a reduction in treatment waiting time over time. Trusts with better staffed and improved EIA clinical structure are likely to initiate definitive treatment earlier in patients with EIA. Disclosure Z. Yang: None. N. Arumalla: None. M.D. Russell: Honoraria; Lilly, Menarini, Galapagos. Grants/research support; NIHR. Other; Pfizer, Janssen, Biogen, and UCB. K. Bechman: Honoraria; Menarini, Galapagos. Grants/research support; NIHR,Versus Arthritis and Pfizer Global Medical Grants for Quality Improvement in Rheumatology Practice. Other; UCB. E. Alveyn: Other; UCB. S. Gallagher: None. E. Price: None. S. Norton: None. J. Galloway: Honoraria; AbbVie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UCB.

A longitudinal cohort study on the use of health and care services by older adults living at home with/without dementia before and during the COVID-19 pandemic: the HUNT study.

Older adults and people with dementia were anticipated to be particularly unable to use health and care services during the lockdown period following the COVID-19 pandemic. To better prepare for future pandemics, we aimed to investigate whether the use of health and care services changed during the pandemic and whether those at older ages and/or dementia experienced a higher degree of change than that observed by their counterparts. Data from the Norwegian Trøndelag Health Study (HUNT4 70 + , 2017-2019) were linked to two national health registries that have individual-level data on the use of primary and specialist health and care services. A multilevel mixed-effects linear regression model was used to calculate changes in the use of services from 18months before the lockdown, (12 March 2020) to 18months after the lockdown. The study sample included 10,607 participants, 54% were women and 11% had dementia. The mean age was 76years (SD: 5.7, range: 68-102years). A decrease in primary health and care service use, except for contact with general practitioners (GPs), was observed during the lockdown period for people with dementia (p < 0.001) and those aged ≥ 80years without dementia (p = 0.006), compared to the 6-month period before the lockdown. The use of specialist health services decreased during the lockdown period for all groups (p ≤ 0.011), except for those aged < 80years with dementia. Service use reached levels comparable to pre-pandemic data within one year after the lockdown. Older adults experienced an immediate reduction in the use of health and care services, other than GP contacts, during the first wave of the COVID-19 pandemic. Within primary care services, people with dementia demonstrated a more pronounced reduction than that observed in people without dementia; otherwise, the variations related to age and dementia status were small. Both groups returned to services levels similar to those during the pre-pandemic period within one year after the lockdown. The increase in GP contacts may indicate a need to reallocate resources to primary health services during future pandemics. The study is registered at ClinicalTrials.gov, with the identification number NCT04792086.

Inpatient Hospital Costs, Emergency Department Visits, and Readmissions for Revision Hip and Knee Arthroplasty

Revision total hip arthroplasty (THA) and total knee arthroplasty (TKA) tremendously burden hospital resources. This study evaluated factors influencing perioperative costs, including emergency department (ED) visits, readmissions, and total costs-of-care within 90 days following revision surgery. A retrospective analysis of 772 revision TKAs and THAs performed on 630 subjects at a single center between January 2007 and December 2019 was conducted. Cost data was available from January 2015 to December 2019 for 277 patients. Factors examined included comorbidities, demographic information, pre-operative Anesthesia Society of Anesthesiologists score, implant selection, and operative indication using mixed-effects linear regression models. Among 772 revisions (425 THA and 347 TKA), 213 patients required an ED visit, and 90 required hospital readmission within 90 days. There were 22.6% of patients who underwent a second procedure after their initial revision. Liver disease was a significant predictor of ED readmission for THA patients (multivariable OR [odds ratio]: 3.473, P = 0.001), while aseptic loosening, osteolysis, or instability significantly reduced the odds of readmission for TKA patients (OR: 0.368, P = 0.014). In terms of ED visits, liver disease increased the odds for THA patients (OR: 1.845, P = 0.100), and aseptic loosening, osteolysis, or instability decreased the odds for TKA patients (OR: 0.223, P < 0.001). Increased age was associated with increased costs in both THA and TKA patients, with significant cost factors including congestive heart failure for TKA patients (OR: $7,308.17, P = 0.004) and kidney disease for THA patients. Revision surgeries took longer than primary ones, with TKA averaging 3.0 hours (1.6 times longer) and THA 2.8 hours (1.5 times longer). Liver disease increases ED readmission risk in revision THA, while aseptic loosening, osteolysis, or instability decreases it in revision TKA. Increased age and CHF are associated with increased costs. These findings inform postoperative care and resource allocation in revision arthroplasty.

Perceived Stress, Blood Biomarkers, and Cognitive Functioning in Older Adults.

There is a substantial gap in knowledge regarding how perceived stress may influence the relationship between serum-measured biomarkers for Alzheimer's disease and cognitive decline. This study consists of 1,118 older adult participants from the Chicago Health and Aging Project (CHAP) (60% Black participants and 63% female participants). Linear mixed effects regression models were conducted to examine the role of perceived stress in the association between three blood biomarkers: total tau (t-tau), glial fibrillary acid protein (GFAP), and neurofilament light chain (NfL) on global cognitive decline. Stratified analysis by stress level was also conducted to evaluate the associations between each blood biomarker and baseline cognitive function and decline. All models adjusted for age, race, sex, education, time, and their interactions with time. The interaction of stress, NfL concentration, and time was statistically significant on global cognition (β = -0.064 (SE = 0.028), p-value = 0.023) and on episodic memory (β = -0.097 (SE = 0.036), p-value = 0.007). Greater stress level worsens the association between high NfL concentration and cognitive decline. Stress management interventions may be helpful to reduce rate of cognitive decline in individuals with high concentrations of NfL.

Peer-Led Symptom Management Intervention to Enhance Resilience in People with Systemic Sclerosis: Mediation Analysis from a Randomized Clinical Trial.

Facilitated self-management interventions have the potential to enhance resilience and well-being. We examined whether resilience is a mediator of improving physical and psychological symptoms for people with systemic sclerosis (SSc) who participated in a 12-week online peer-led symptom management intervention. We conducted a secondary data analysis from a randomized control trial comparing a peer health coached intervention to a waitlist control. Participants completed the Connor-Davidson Resilience Scale, the Functional Assessment of Chronic Illness Therapy-Fatigue scale, and the Patient Reported Outcomes Measurement Information System measures of pain interference and depressive symptoms at the baseline and at weeks 6 and 12. Linear mixed effect regression models were used to assess the effect of intervention on changes in resilience. Causal mediation analyses were conducted to examine whether changes in resilience at week 12 mediated intervention effects on changes in fatigue, pain interference, and depressive symptoms at week 12. One hundred and seventy-three eligible participants were enrolled. Participants in the intervention group reported improvements in resilience (p < .001). These changes in resilience mediated the intervention effects on fatigue with indirect effect of -1.41 (95% Confidence Interval [CI], -2.41 to -0.41), pain interference of -0.86 (95% CI, -1.65 to -0.08), and depressive symptoms of -1.99 (95% CI, -3.16 to -0.81). For participants in the intervention who had positive improvements in their physical and psychological symptoms, increased resilience was a mechanism for these improvements. These findings support the importance of addressing resilience to improve symptoms in similar SSc interventions.

Association of symptom severity and cerebrospinal fluid alterations in recent onset psychosis in schizophrenia-spectrum disorders – An individual patient data meta-analysis

Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorderś(SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta-analysis, investigating the association of BCB disruption and cerebrospinal fluid (CSF) alterations with symptom severity in first-episode psychosis (FEP) and recent onset psychotic disorder (ROP) individuals, with a focus on sex-related differences. Data was collected from PubMed and EMBASE databases. FEP, ROP and high-risk syndromes for psychosis IPD were included if routine basic CSF-diagnostics were reported. Risk of bias of the included studies was evaluated. Random-effects meta-analyses and mixed-effects linear regression models were employed to assess the impact of BCB alterations on symptom severity. Published (6 studies) and unpublished IPD from n = 531 individuals was included in the analyses. CSF was altered in 38.8 % of individuals. No significant differences in symptom severity were found between individuals with and without CSF alterations (SMD = -0.17, 95 %CI −0.55–0.22, p = 0.341). However, males with elevated CSF/serum albumin ratios or any CSF alteration had significantly higher positive symptom scores than those without alterations (SMD = 0.34, 95 %CI 0.05–0.64, p = 0.037 and SMD = 0.29, 95 %CI 0.17–0.41p = 0.005, respectively). Mixed-effects and simple regression models showed no association (p > 0.1) between CSF parameters and symptomatic outcomes. No interaction between sex and CSF parameters was found (p > 0.1). BCB disruption appears highly prevalent in early psychosis and could be involved in positive symptomś severity in males, indicating potential difficult-to-treat states. This work highlights the need for considering BCB breakdownand sex-related differences in SSDs clinical trials and treatment strategies.