Development of antibody levels and subsequent decline in individuals with vaccine induced and hybrid immunity to SARS-CoV-2.

OBJECTIVES: This study aimed to compare antibody trajectories among individuals with SARS-CoV-2 hybrid and vaccine-induced immunity. METHODS: Danish adults receiving three doses of BTN162b2 or mRNA-1237 were included prior to first vaccination (Day0). SARS-CoV-2 anti-spike IgG levels were assessed before each vaccine dose, at Day90, Day180, 28 days after 3rd vaccination (Day251), Day365, and prior to 4th vaccination (Day535). SARS-CoV-2 PCR results were extracted from the national microbiology database. Mixed-effect multivariable linear regression investigated the impact of hybrid-immunity (stratified into 4 groups: no hybrid immunity, PCR+ prior to 3rd dose, PCR+ after 3rd dose and before Day365, PCR+ after Day365) on anti-spike IgG trajectories. RESULTS: 4,936 individuals were included, 47% developed hybrid-immunity. Anti-spike IgG increases were observed in all groups at Day251, with the highest levels in those PCR+ prior to 3rd dose (Geometric Mean; 535,647AU/mL vs. 374,665AU/mL with no hybrid-immunity, p=<0.0001). Further increases were observed in participants who developed hybrid immunity after their 3rd dose. Anti-spike IgG levels declined from Day 251-535 in individuals without hybrid-immunity and in those who developed hybrid-immunity prior to their 3rd dose, with lower rate of decline in those with hybrid-immunity. CONCLUSION: Hybrid-immunity results in higher and more durable antibody trajectories in vaccinated individuals.

Screening for Metal-Chelating Activity in Potato Protein Hydrolysates Using Surface Plasmon Resonance and Peptidomics.

Metal-catalyzed lipid oxidation is a major factor in food waste, as it reduces shelf life. Addressing this issue, our study investigates the potential of hydrolysates derived from potato protein, a by-product of potato starch production, as metal-chelating antioxidants. Through sequential enzymatic hydrolysis using alcalase or trypsin combined with Flavourzyme, we produced various hydrolysates, which were then fractionated using ultrafiltration. Using a combination of peptidomics and bioinformatics, we predicted the presence of metal-chelating and free radical-scavenging peptides across all hydrolysate fractions, with a trend indicating a higher content of antioxidant peptides in lower molecular weight fractions. To validate these predictions, we utilized surface plasmon resonance (SPR) and a 9-day emulsion storage experiment. While SPR demonstrated potential in identifying antioxidant activity, it faced challenges in differentiating between hydrolysate fractions due to significant standard errors. In the storage experiment, all hydrolysates showed lipid oxidation inhibition, though not as effectively as ethylenediaminetetraacetic acid (EDTA). Remarkably, one fraction (AF13) was not significantly different (p < 0.05) from EDTA in suppressing hexanal formation. These results highlight SPR and peptidomics/bioinformatics as promising yet limited methods for antioxidant screening. Importantly, this study reveals the potential of potato protein hydrolysates as antioxidants in food products, warranting further research.

SuPAR, biomarkers of inflammation, and severe outcomes in patients hospitalized for COVID-19: The International Study of Inflammation in COVID-19.

Severe coronavirus disease 2019 (COVID-19) is a hyperinflammatory syndrome. The biomarkers of inflammation best suited to triage patients with COVID-19 are unknown. We conducted a prospective multicenter observational study of adult patients hospitalized specifically for COVID-19 from February 1, 2020 to October 19, 2022. Biomarkers measured included soluble urokinase plasminogen activator receptor (suPAR), C-reactive protein, interleukin-6, procalcitonin, ferritin, and D-dimer. In-hospital outcomes examined include death and the need for mechanical ventilation. Patients admitted in the United States (US, n = 1962) were used to compute area under the curves (AUCs) and identify biomarker cutoffs. The combined European cohorts (n = 1137) were used to validate the biomarker cutoffs. In the US cohort, 356 patients met the composite outcome of death (n = 197) or need for mechanical ventilation (n = 290). SuPAR was the most important predictor of the composite outcome and had the highest AUC (0.712) followed by CRP (0.642), ferritin (0.619), IL-6 (0.614), D-dimer (0.606), and lastly procalcitonin (0.596). Inclusion of other biomarkers did not improve discrimination. A suPAR cutoff of 4.0 ng/mL demonstrated a sensitivity of 95.4% (95% CI: 92.4%-98.0%) and negative predictive value (NPV) of 92.5% (95% CI: 87.5%-96.9%) for the composite outcome. Patients with suPAR < 4.0 ng/mL comprised 10.6% of the cohort and had a 0.8% probability of the composite outcome. Applying this cutoff to the validation cohort yielded a sensitivity of 93.8% (90.4%-96.7%) and NPV of 95.5% (93.1%-97.8%) for the composite outcome. Among commonly measured biomarkers, suPAR offered stronger discriminatory ability and may be useful in triaging low-risk patients with COVID-19.

Heavy antiretroviral exposure and exhausted/limited antiretroviral options: predictors and clinical outcomes.

OBJECTIVES: People with HIV and extensive antiretroviral exposure may have limited/exhausted treatment options (LExTO) due to resistance, comorbidities, or antiretroviral-related toxicity. Predictors of LExTO were investigated in the RESPOND cohort. METHODS: Participants on ART for at least 5 years were defined as having LExTO when switched to at least two anchor agents and one third antiretroviral (any class), a two-drug regimen of two anchor agents (excluding rilpivirine with dolutegravir/cabotegravir), or at least three nucleoside reverse transcriptase inhibitors. Baseline was the latest of January 1, 2012, cohort enrolment or 5 years after starting antiretrovirals. Poisson regression modeled LExTO rates and clinical events (all-cause mortality, non-AIDS malignancy, cardiovascular disease [CVD], and chronic kidney disease [CKD]). RESULTS: Of 23 827 participants, 2164 progressed to LExTO (9.1%) during 130 061 person-years follow-up (PYFU); incidence 1.66/100 PYFU (95% CI 1.59-1.73). Predictors of LExTO were HIV duration more than 15 years (vs. 7.5-15; adjusted incidence rate ratio [aIRR] 1.32; 95% CI 1.19-1.46), development of CKD (1.84; 1.59-2.13), CVD (1.64; 1.38-1.94), AIDS (1.18; 1.07-1.30), and current CD4 + cell count of 350 cells/µl or less (vs. 351-500 cells/µl, 1.51; 1.32-1.74). Those followed between 2018 and 2021 had lower rates of LExTO (vs. 2015-2017; 0.52; 0.47-0.59), as did those with baseline viral load of 200 cp/ml or less (0.46; 0.40-0.53) and individuals under 40. Development of LExTO was not significantly associated with clinical events after adjustment for age and current CD4, except CKD (1.74; 1.48-2.05). CONCLUSION: Despite an aging and increasingly comorbid population, we found declining LExTO rates by 2018-2021, reflecting recent developments in contemporary ART options and clinical management. Reassuringly, LExTO was not associated with a significantly increased incidence of serious clinical events apart from CKD.

Social isolation, loneliness, and inflammation: A multi-cohort investigation in early and mid-adulthood.

Social isolation and loneliness have been associated with poor health and increased risk for mortality, and inflammation might explain this link. We used data from the Danish TRIAGE Study of acutely admitted medical patients (N = 6,144, mean age 60 years), and from two population-representative birth cohorts: the New Zealand Dunedin Longitudinal Study (N = 881, age 45) and the UK Environmental Risk (E-Risk) Longitudinal Twin Study (N = 1448, age 18), to investigate associations of social isolation with three markers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer inflammation marker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to index systemic chronic inflammation. In the TRIAGE Study, socially isolated patients (those living alone) had significantly higher median levels of suPAR (but not CRP or IL-6) compared with patients not living by themselves. Social isolation prospectively measured in childhood was longitudinally associated with higher CRP, IL-6, and suPAR levels in adulthood (at age 45 in the Dunedin Study and age 18 in the E-Risk Study), but only suPAR remained associated after controlling for covariates. Dunedin Study participants who reported loneliness at age 38 or age 45 had elevated suPAR at age 45. In contrast, E-Risk Study participants reporting loneliness at age 18 did not show any elevated markers of inflammation. In conclusion, social isolation was robustly associated with increased inflammation in adulthood, both in medical patients and in the general population. It was associated in particular with systemic chronic inflammation, evident from the consistently stronger associations with suPAR than other inflammation biomarkers.

The Impact of Vaccination against SARS-CoV-2 on Health Outcomes and Hospital Visits after Omicron Infection in Children and Adolescents Aged 5-18 Years: A Danish Nation-Wide Cohort Study.

This study investigates the impact of vaccination against SARS-CoV-2 on health outcomes and hospital contacts in children and adolescents aged 5-18 years infected with the SARS-CoV-2 Omicron variant, comparing previously vaccinated with unvaccinated. Using national register data, vaccinated and unvaccinated Danish children and adolescents with a positive SARS-CoV-2 test between 1 January and 31 March 2022 (Omicron dominance period) were included. The Prior Event Rate Ratio (PERR) was used to explore differences in hospital contacts (hospitalizations and emergency room (ER) visits), while Inverse Treatment Probability Weighted (IPW) risk ratios were used to explore the risk of severe health outcomes within six weeks following SARS-CoV-2 infection. Vaccinated 5-11-year-old girls had fewer visits to the ER compared to unvaccinated ones, PERR 0.92 (95% CI 0.84-1.00). Vaccinated 5-11-year-old boys had fewer hospitalizations (PERR 0.79 (0.64-0.99)) and more ER visits (PERR 1.13 (1.04-1.22)) compared to unvaccinated ones. An unadjusted and significant lower risk of febrile seizure among vaccinated 5-11-year-olds compared to unvaccinated ones was found (risk ratio 0.12 (0.04-0.39), p ≤ 0.01. No significant differences were found for severe conditions or for croup or pneumonia in either age group. The results indicate a modest protective effect of the vaccine in terms of hospital contacts, but no protective effect on health outcomes after SARS-CoV-2 Omicron infection in this population of Danish children and adolescents.

Evaluating Drug Prescription Patterns in Undiagnosed Common Variable Immunodeficiency Patients.

OBJECTIVE: To compare the consumption of antibiotics (AB), systemic steroids, and inhaled bronchodilators/glucocorticoids in the 3 years preceding the diagnosis of common variable immunodeficiency (CVID) among CVID patients and matched controls and to estimate whether the level of consumption was associated with the risk of a subsequent CVID diagnosis. METHODS: We conducted a nested case-control study, identifying all individuals (n=130 cases) diagnosed with CVID in Denmark (1994-2014) and 45 age- and sex-matched population controls per case (n=5850 controls) from national registers. Drug consumption was estimated as defined daily doses per person-year. We used conditional logistic regression to compute odds ratios and 95% confidence intervals. RESULTS: In the 3 years preceding a CVID diagnosis, we observed more frequent and higher consumption of all three drug classes. The association between consumption and risk of subsequent CVID diagnosis was statistically significant for all drug classes. The association was stronger with higher consumption and shorter time to CVID diagnosis. The fraction of cases compared to the controls redeeming ≥1 prescription of the included drugs during the study period was higher for AB (97% vs 52%), systemic steroids (35% vs 7.4%), and inhaled bronchodilators/glucocorticoids (46% vs 11.7%) (p<0.001). CONCLUSION: CVID patients have significantly higher use of AB, systemic steroids, and inhaled bronchodilators/glucocorticoids in the 3 years preceding CVID diagnosis than controls. Prescribing these drugs in primary healthcare could be an opportunity to consider (proactive) screening for CVID. Further studies are needed to identify optimal prescription cutoffs that could endorse its inclusion in public health policies.

Should oral care be about more than a gut feeling? A qualitative study investigating patients' and healthcare professionals' experiences.

AIM: To explore patients' and healthcare professionals' (HCPs) experiences of oral care during hospitalisation to identify needs and challenges. BACKGROUND: Daily oral care is important to patients' health and well-being, to prevent diseases in the oral cavity, systemic infections and increased morbidity, which subsequently can lead to prolonged hospitalisation and, at worst, increased mortality. Despite this knowledge, oral care is a neglected part of nursing practice. Studies do not clearly identify barriers regarding oral care, as the existing knowledge is inadequate. DESIGN: A qualitative study exploring participants' experiences to gain new in-depth knowledge of oral care among hospitalised patients. METHODS: A phenomenological-hermeneutic approach was applied. Participant observations were conducted on five hospital wards, combined with individual semi-structured interviews with 16 patients and 15 HCP. Data analysis was based on Ricoeur's theory of narrative and interpretation. RESULTS: Four themes describing the challenges regarding oral care emerged: Oral care as a gut feeling; oral care fades into the background; even self-reliant patients need help with oral care; and the mouth reflects the life lived. CONCLUSIONS: The identified challenges show there is a need for improvement in the health professional approach to oral care in nursing practice. Focus on increasing HCPs' knowledge, skills and competences can increase their nursing agency and support patients' self-care capacity. IMPACT: Investigation of oral care during hospitalisation revealed four main challenges concerning both patients' and HCPs' lack of knowledge and awareness of oral care. Thus, patients and HCPs should be included in developing solutions to improve oral care in nursing practice. REPORTING METHODS: The COREQ criteria for reporting qualitative research were adhered to. PATIENT CONTRIBUTION: A patient representative was involved in the discussion of the proposal, conduct and results of the study.

Thoracic ultrasonographic and clinical findings at 12-month follow-up of patients admitted with COVID-19.

Introduction: Thoracic ultrasound (TUS) has proven useful in the diagnosis, risk stratification and monitoring of disease progression in patients with coronavirus disease 2019 (COVID-19). However, utility in follow-up is poorly described. To elucidate this area, we performed TUS as part of a 12-month clinical follow-up in patients previously admitted with COVID-19 and correlated findings with clinical assessment and pulmonary function tests. Methods: Adult patients discharged from our hospital following admission with COVID-19 during March to May 2020 were invited to a 12-month follow-up. Enrolled patients were interviewed regarding persisting or newly developed symptoms in addition to TUS, spirometry and a 6-min walk test. Patients were referred to high-resolution computed tomography (HRCT) of the lungs if suspicion of pulmonary fibrosis was raised. Results: Forty patients were enrolled in the study of whom had 13 developed acute respiratory distress syndrome (ARDS) during admission. Patients with ARDS were more prone to experience neurological symptoms at follow-up (p = 0.03) and showed more B-lines on TUS (p = 0.008) but did not otherwise differ significantly in terms of pulmonary function tests. Four patients had pathological findings on TUS where subsequent diagnostics revealed that two had interstitial lung abnormalities and two had heart failure. These four patients presented with a significantly lower diffusing capacity of lung for carbon monoxide (p=0.03) and 6-min walking distance (p=0.006) compared to the remaining 36 patients without ultrasound pathology. No significant difference was observed in spirometry values of % of predicted FEV1 (p=0.49) or FVC (p=0.07). No persisting cardiovascular pathology was observed in patients without ultrasonographic pathology. Conclusion: At 12-month after admission with COVID-19, a follow-up combining TUS, clinical assessment, and pulmonary function tests may improve the selection of patients requiring further diagnostic investigations such as HRCT or echocardiography.

Missed Opportunities to Diagnose Common Variable Immunodeficiency: a Population-Based Case-Control Study Identifying Indicator Diseases for Common Variable Immunodeficiency.

PURPOSE: Delayed diagnosis of common variable immunodeficiency (CVID) remains a serious problem. We investigated whether some diseases diagnosed during out-patient visits or admission to hospitals could act as indicator conditions for CVID diagnosis. METHODS: In this nested case-control study, we identified 128 cases diagnosed with CVID in Denmark (1999-2013) and 640 age-, gender-, and region-matched controls. We obtained data on diseases diagnosed at hospitals in the five years before CVID diagnosis from The National Hospital Registry. We grouped hospital diagnoses in 33 major disease categories and 210 subcategories. We used conditional logistic regression to calculate the odds ratios (OR) and 95% confidence intervals (CI) to estimate associations between disease exposure and subsequent CVID. RESULTS: During the five years preceding a CVID diagnosis, cases had four times as many hospital contacts as the controls (p < 0.001). A diagnosis in 18 major disease categories showed a significant OR for subsequent diagnosis of CVID. The most substantial association with a subsequent CVID diagnosis was a diagnosis of lower respiratory tract infections (OR: 29.9; 95% CI: 14.2-63.2) and lung diseases (35.1; 15.0-82.5). We observed a similar association when we removed the last year before diagnosis from analysis and overall, in the years < 1, ≥ 1-3, and ≥ 3-5 before diagnosis, although the absolute number of exposures was small. Twenty-eight specific diseases displayed an at least 3-fold risk of subsequent CVID diagnosis. CONCLUSION: Targeted screening for antibody deficiency in patients diagnosed with specific diseases associated with CVID may lead to earlier CVID diagnosis and treatment and thereby potentially reduced morbidity and mortality.

Misuse of multinomial logistic regression in stroke related health research: A systematic review of methodology.

Multinomial logistic regression (MLR) is often used to model the association between a nominal outcome variable and one or more covariates. The results of MLR are interpreted as relative risk ratios (RRR) and warrant a more coherent interpretation than ordinary logistic regression. Some authors compare the results of MLR to ordinal logistic regression (OLR), irrespective of the fact that these estimate different quantities. We aim to investigate the time trends in the use and misuse of MLR in studies including stroke patients, specifically the extent to which (1) the results are denoted as anything other than RRR, (2) comparisons are made of results with results of OLR and (3) results have been interpreted coherently. Secondarily, we examine the use of model validation techniques in studies with predictive aims. We searched EMBASE and PubMed for articles using MLR on populations of stroke patients. Identified studies were screened, and information pertaining to our aims was extracted. A total of 285 articles were identified through a systematic literature search, and 68 of these were included in the review. Of these, 60 articles (88%) did not denote exponentiated coefficients of MLR as relative risk ratios but rather some other measure. Additionally, 63 articles (93%) interpreted the results of MLR in a non-coherent manner. Two articles attempted to compare MLR results with those of OLR. Nine studies attempted to use MLR for predictive means, and three used relevant validation techniques. From these findings, it is clear that the interpretation of MLR is often suboptimal.

Symptom-Specific Hospital Contacts in 12-18-Year-Olds Vaccinated against COVID-19: A Danish Register-Based Cohort Study.

In this register-based real-life cohort study, changes in symptom-specific hospital contacts among 12-18-year-olds following two doses of the BNT162b2 COVID-19 vaccine compared to unvaccinated peers were investigated. Using national register data, vaccinated and unvaccinated adolescents were sex and age-matched each week during the inclusion period from May to September 2021. Symptom-specific hospital contacts covering ICD-10 R diagnoses were assessed before first the vaccine dose and after the second vaccine dose. Taking previous rates of symptom-specific hospital contacts into account, differences between vaccinated and unvaccinated adolescents were found. For some hospital contacts, higher rates were seen among the vaccinated, and for others, higher rates were seen among the unvaccinated. Unspecific cognition symptoms may be important to monitor in vaccinated girls, and likewise for throat and chest pain in vaccinated boys within the first months post-vaccination. In perspective, symptom-specific hospital contacts after vaccination against COVID-19 must be assessed by taking the risk of infection and symptoms following COVID-19 infection into account.

Socioenvironmental Adversity and Adolescent Psychotic Experiences: Exploring Potential Mechanisms in a UK Longitudinal Cohort.

BACKGROUND AND HYPOTHESIS: Children exposed to socioenvironmental adversities (eg, urbanicity, pollution, neighborhood deprivation, crime, and family disadvantage) are more likely to subsequently develop subclinical psychotic experiences during adolescence (eg, hearing voices, paranoia). However, the pathways through which this occurs have not been previously investigated. We hypothesized that cognitive ability and inflammation would partly explain this association. STUDY DESIGN: Data were utilized from the Environmental-Risk Longitudinal Twin Study, a cohort of 2232 children born in 1994-1995 in England and Wales and followed to age 18. Socioenvironmental adversities were measured from birth to age 10 and classified into physical risk (defined by high urbanicity and air pollution) and socioeconomic risk (defined by high neighborhood deprivation, neighborhood disorder, and family disadvantage). Cognitive abilities (overall, crystallized, fluid, and working memory) were assessed at age 12; and inflammatory markers (C-reactive protein, interleukin-6, soluble urokinase plasminogen activator receptor) were measured at age 18 from blood samples. Participants were interviewed at age 18 regarding psychotic experiences. STUDY RESULTS: Higher physical risk and socioeconomic risk were associated with increased odds of psychotic experiences in adolescence. The largest mediation pathways were from socioeconomic risk via overall cognitive ability and crystallized ability, which accounted for ~11% and ~19% of the association with psychotic experiences, respectively. No statistically significant pathways were found via inflammatory markers in exploratory (partially cross-sectional) analyses. CONCLUSIONS: Cognitive ability, especially crystallized ability, may partly explain the association between childhood socioenvironmental adversity and adolescent psychotic experiences. Interventions to support cognitive development among children living in disadvantaged settings could buffer them against developing subclinical psychotic phenomena.

Systematic review and meta-analysis of the effect of adverse childhood experiences (ACEs) on brain-derived neurotrophic factor (BDNF) levels.

There is continued interest in identifying dysregulated biomarkers that mediate associations between adverse childhood experiences (ACEs) and negative long-term health outcomes. However, little is known regarding how ACE exposure modulates neural biomarkers to influence poorer health outcomes in ACE-exposed children. To address this, we performed a systematic review and meta-analysis of the impact of ACE exposure on Brain Derived Neurotrophic Factor (BDNF) levels - a neural biomarker involved in childhood and adult neurogenesis and long-term memory formation. Twenty-two studies were selected for inclusion within the systematic review, ten of which were included in meta-analysis. Most included studies retrospectively assessed impacts of childhood maltreatment in clinical populations. Sample size, BDNF protein levels in ACE-exposed and unexposed subjects, and standard deviations were extracted from ten publications to estimate the BDNF ratio of means (ROM) across exposure categories. Overall, no significant difference was found in BDNF protein levels between ACE-exposed and unexposed groups (ROM: 1.08; 95 % CI: 0.93-1.26). Age at sampling, analyte type (e.g., sera, plasma, blood), and categories of ACE exposure contributed to high between-study heterogeneity, some of which was minimized in subset-based analyses. These results support continued investigation into the impact of ACE exposure on neural biomarkers and highlight the potential importance of analyte type and timing of sample collection on study results.

Experience with sotrovimab treatment of SARS-CoV-2-infected patients in Denmark.

AIMS: To evaluate the experience with use of sotrovimab following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in high-risk groups. METHODS: In a nationwide, population-based cohort study, we identified all individuals treated with sotrovimab (N = 2933) and stratified them by 4 high-risk groups: (A) malignant haematological disease, (B) solid organ transplantation, (C) anti-CD20 therapy ≤1 year and (D) other risks. Cox regression analysis was used to calculate hazard ratios for hospitalization, death and associated prognostic factors. RESULTS: Of 2933 sotrovimab-treated individuals, 83% belonged to high-risk groups (37.6% haematological malignancy, 27.4% solid organ transplantation and 17.5% treatment with anti-CD20 ≤1 year). Only 17.8% had other risks (11.8% were pregnant, 10.7% primary immunodeficiency, 21.2% other malignancy, 4.3% received anti-CD20 >1 year and 52.0% other/unknown causes). Within 90 days of infusion, 30.2% were hospitalized and 5.3% died. The main prognostic factors were the predefined high-risk groups, mainly malignant haematological disease and age ≥65 years. Number of COVID-19 vaccines (≥3) was associated with a decreased risk of hospitalization. The Delta but not the Omicron BA.2 variant was associated with a higher risk of death compared to the BA.1 variant. CONCLUSION: More than 90% of the patients treated with sotrovimab belonged to the very high-risk groups as described in the Danish guidelines. Sotrovimab-treated individuals remained at a high risk of hospitalization and death which was strongly associated with the underlying immunocompromised state and age. Having received >3 COVID-19 vaccines was association with decreased risk of death and hospitalization.

Recent abacavir use and incident cardiovascular disease in contemporary-treated people with HIV.

OBJECTIVE: Assessing whether the previously reported association between abacavir (ABC) and cardiovascular disease (CVD) remained amongst contemporarily treated people with HIV. DESIGN: Multinational cohort collaboration. METHODS: RESPOND participants were followed from the latest of 1 January 2012 or cohort enrolment until the first of a CVD event (myocardial infarction, stroke, invasive cardiovascular procedure), last follow-up or 31 December 2019. Logistic regression examined the odds of starting ABC by 5-year CVD or chronic kidney disease (CKD) D:A:D risk score. We assessed associations between recent ABC use (use within the past 6 months) and risk of CVD with negative binomial regression models, adjusted for potential confounders. RESULTS: Of 29 340 individuals, 34% recently used ABC. Compared with those at low estimated CVD and CKD risks, the odds of starting ABC were significantly higher among individuals at high CKD risk [odds ratio 1.12 (95% confidence interval = 1.04-1.21)] and significantly lower for individuals at moderate, high or very high CVD risk [0.80 (0.72-0.88), 0.75 (0.64-0.87), 0.71 (0.56-0.90), respectively]. During 6.2 years of median follow-up (interquartile range; 3.87-7.52), there were 748 CVD events (incidence rate 4.7 of 1000 persons-years of follow up (4.3-5.0)]. The adjusted CVD incidence rate ratio was higher for individuals with recent ABC use [1.40 (1.20-1.64)] compared with individuals without, consistent across sensitivity analyses. The association did not differ according to estimated CVD (interaction P  = 0.56) or CKD ( P  = 0.98) risk strata. CONCLUSION: Within RESPOND's contemporarily treated population, a significant association between CVD incidence and recent ABC use was confirmed and not explained by preferential ABC use in individuals at increased CVD or CKD risk.

Childhood Adversity and Midlife Health: Shining a Light on the Black Box of Psychosocial Mechanisms.

Adverse childhood experiences (ACEs) are associated with poorer health, which has spurred public health efforts to reduce the number of adverse events children experience. Unfortunately, it is unlikely that all ACEs can be prevented. For adults who already experienced ACEs in childhood, what psychological, social, and behavioral intervention targets might reduce risk for negative health outcomes? To provide insight into the "black box" of psychosocial mechanisms linking ACEs to poor health, our study used data from the Dunedin Study, a longitudinal cohort assessed from birth to age 45. Mediation models (N = 859) were used to examine whether candidate psychosocial variables in adulthood explained the association between childhood ACEs and health in midlife. Potential psychosocial mediators included stressful life events, perceived stress, negative emotionality, and health behaviors. Children who experienced more ACEs had poorer health in midlife. They also had significantly more stressful life events, more perceived stress, more negative emotionality, and unhealthier behaviors as adults. These mediators were each independently associated with poorer health in midlife and statistically mediated the association between ACEs and midlife health. Health behaviors evidenced the strongest indirect effect from ACEs to midlife health. Together, these psychosocial mediators accounted for the association between ACEs in childhood and health three decades later. Public health efforts to mitigate the health consequences of ACEs could aim to reduce the stressful life events people experience, reduce negative emotionality, reduce perceived stress, or improve health behaviors among adults who experienced childhood adversity.

Outcomes following severe acute respiratory syndrome coronavirus 2 infection among individuals with and without HIV in Denmark.

OBJECTIVE: To compare the risk of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test and coronavirus disease 2019 (COVID-19) outcomes in people with HIV (PWH) with the general population, and estimate the association with vaccination status. DESIGN: A nationwide, population based, matched cohort study. METHODS: We included all Danish PWH ≥18 years ( n  = 5276) and an age and sex-matched general population cohort ( n  = 42 308). We used Cox regression analyses to calculate (adjusted) incidence rate ratios [(a)IRR] and further stratified and restricted the analyses. RESULTS: We observed no major difference in risk of first positive SARS-CoV-2 test [aIRR: 0.8 (95% confidence interval (CI): 0.8-0.9)], but a higher risk of first hospital contact with COVID-19 and hospitalization with severe COVID-19 for PWH vs. controls [IRR: 2.0; (1.6-2.5), 1.8 (1.4-2.3)]. Risk of first hospitalization decreased substantially in PWH with calendar time [first half of year 2022 vs. 2020 IRR: 0.3; (0.2-0.6)], whereas the risk compared to population controls remained almost twofold increased. We did not observe increased risk of death after SARS-CoV-2 infection [aIRR: 0.7 (95% CI: 0.3-2.0)]. Compared to PWH who had received two vaccines PWH who receiving a third vaccine had reduced risk of first positive SARS-CoV-2 test, death (individuals ≥60years) and hospitalization [aIRR: 0.9 (0.7-1.0); 0.2 (0.1-0.7); 0.6 (0.2-1.2)]. CONCLUSION: PWH have almost the same risk of a positive SARS-CoV-2 test as the general population. Although risk of hospital contacts and severe outcomes following SARS-CoV-2 infection is increased, the risk of death does not seem to be substantially increased. Importantly, a third vaccine is associated with reduced risk of infection, and death.

Self-rated health and chronic inflammation are related and independently associated with hospitalization and long-term mortality in the general population.

The subjective indicator of health self-rated health (SRH) and the chronic inflammation biomarker soluble urokinase plasminogen activator receptor (suPAR) are both robust predictors of healthcare use and mortality. However, the possible relationship between SRH and suPAR in the assessment of hospitalization and mortality risk is unknown. We used data from the Danish population-based Inter99 cohort to examine the association between SRH and suPAR and test their individual and combined associations with 2-year risk of acute hospitalization and 5- and 15-year mortality. SRH and serum suPAR levels were measured in 5490 participants (median age 45.1 years, 48.7% men). Poorer SRH was associated with elevated suPAR. In unadjusted analyses, SRH and suPAR were individually associated with higher risks of acute hospitalization and mortality, and both measures remained independently associated with higher risks of hospitalization and 15-year mortality after mutual adjustments. The association of suPAR with mortality was stronger in poorer SRH categories, and when combined, SRH and suPAR could identify different groups of individuals with increased risk of acute hospitalization and mortality. Both SRH and suPAR were independently associated with risk of acute hospitalization and mortality, and different combinations of the two measures could identify different groups of individuals at increased risk.

Short- and Long-Term Self-Reported Symptoms in Adolescents Aged 12-19 Years after Vaccination against SARS-CoV-2 Compared to Adolescents Not Vaccinated-A Danish Retrospective Cohort Study.

This study investigated self-reported short- and long-term symptoms among adolescents receiving the BNT162b2 (Pfizer/BioNTech) vaccine against SARS-CoV-2 and those who did not. A retrospective cohort study based on Danish national survey (collected between 20 July and 15 September 2021) and register data was conducted. Differences in short-term (<14 days) and long-term (>two months) symptoms were explored using logistic regression adjusted for confounders. A total of 747 vaccinated (first dose n = 326; second dose n = 421) and 6300 unvaccinated adolescents were included in analyses of short-term symptoms and 32 vaccinated and 704 unvaccinated adolescents in long-term symptom analyses. In the first 14 days after the first and second vaccine dose the most reported symptoms included headache and muscle or joint symptoms. In both vaccinated and unvaccinated adolescents, the 15−19-year-olds reported significantly higher proportions of all symptoms compared to the 12−14-year-olds. After the second vaccine dose vaccinated 12−14-year-olds reported significantly more headache in adjusted analyses (OR 2.20 (95% CI 1.24; 3.90)). Among the 15−19-year-olds, significantly more vaccinated adolescents reported gastrointestinal symptoms (1.38 (1.06; 1.81)), headache (1.66 (1.24; 2.22)), and tiredness (1.44 (1.08; 1.93)). No differences were found in long-term symptoms. Vaccinated adolescents reported significantly more short-term symptoms including headache, tiredness, and gastrointestinal symptoms after the second vaccine dose than unvaccinated adolescents. Long-term symptom results should be interpreted with caution due to limited sample size.