Social networks and COVID-19 vaccination intention in Dutch middle-aged and older adults in 2020: Insights into individual, interpersonal, community, and societal determinants - The SaNAE study.

Background: Social networks, our social relationships, influence the spread of infectious diseases and preventive behaviors such as vaccination. Here, we aimed to assess which individual, interpersonal (social network characteristics), community and societal factors are associated with coronavirus disease 2019 (COVID-19) vaccination intention during the second wave of the COVID-19 pandemic in 2020, prior to vaccine availability. Methods: This cross-sectional study collected primary data from 5,001 community-dwelling adults aged 40 years and older in the Netherlands, using an online questionnaire from August and November 2020. COVID-19 vaccination intention was measured by assessing whether respondents were willing to receive a COVID-19 vaccination if the vaccines became available. Associations between individual (sociodemographic variables, health, health concerns), interpersonal (social network characteristics including structure, function, and quality), community (social and labor participation) and societal factors (degree of urbanization), and the outcome variables COVID-19 vaccination intention (yes vs no, yes vs unsure, unsure vs no) were assessed in stepwise multivariable logistic regression analyses. p-values < 0.05 indicated statistical significance. Results: Among participants (N = 3,396), 59 % reported a positive intention to vaccinate, 35 % were unsure, and 6 % had no intention. Men, individuals of older age, those with a college or university degree, those concerned about their personal and family health, and knowledge about protecting oneself from the virus were more likely to have the intention to vaccinate (versus no intention). Interpersonal factors associated included having a larger network size (social network structure) and a larger proportion of informational supporters (social network function). Living outside of urban areas, a societal factor, was associated with vaccination intention (versus no intention). Conclusion: This study identified key factors influencing COVID-19 vaccination intention. Health promotion efforts should address not only individual factors but also incorporate the social environment. Our findings highlight the importance of organizing social networks to mobilize social support for pandemic preparedness.

Enlisting toddler cooperation through structure and autonomy support: The amplifying role of suboptimal relationship mutuality.

Regular repair of normative mother-toddler conflict is required for relational health; yet, we still need improved delineation of regulation strategies that can promote child cooperation. Contemporary conceptualizations of positive parenting propose that structure and autonomy support each facilitate children's optimal engagement; however, toddler studies rarely address their joint impact and conditional moderation. This observational study examined both dimensions in predicting cooperation among 106 U.S. 30-month-olds and their primarily European-American mothers during a demanding request situation. We also assessed mutuality, an indicator of mother-child relationship quality, from two situations with minimized power differentials to explore whether it moderated associations. Regression analyses confirmed the unique and additive impact of both maternal behavioral dimensions in predicting toddler cooperation and also an interaction effect such that the positive association between maternal autonomy support and toddlers' level of cooperation was accentuated depending on the dyads' mutuality. Results suggest that maternal structure and autonomy support may serve as effective approaches for enlisting or maintaining child cooperation during hierarchical negotiations, and that suboptimal relationship mutuality magnifies toddlers' responses to maternal levels of autonomy support. Findings are likely relevant to parenting programs that advance mother-child relational health during the transition from infancy to early childhood.

Para el bienestar de la relación se requiere una regular reparación del conflicto normativo entre madre­niño pequeñito; aun así, necesitamos mejorados delineamientos de las estrategias de regulación que puedan promover la cooperación del niño. Las conceptualizaciones contemporáneas de una crianza positiva proponen que tanto el apoyo de la estructura como de la autonomía facilitan por su parte la participación óptima de los niños; sin embargo, los estudios sobre niños pequeñitos raramente abordan su impacto conjunto y la moderación condicional. Este estudio observacional examinó ambas dimensiones en cuanto a predecir la cooperación entre 106 niños de 30 meses de edad, de Estados Unidos, y sus primariamente euroamericanas mamás durante una pedida situación exigente. También evaluamos la mutualidad, un indicador de la calidad de la relación madre­niño, a partir de dos situaciones con diferenciales de poder minimizados para explorar si la ésta moderaba las asociaciones. Los análisis de regresión confirmaron el singular y agregado impacto de ambas dimensiones del comportamiento materno para predecir la cooperación del niño pequeñito y también un efecto de interacción de manera que la asociación positiva entre el apoyo de autonomía materna y el nivel de cooperación de los niños pequeñitos se acentuó dependiendo de la mutualidad de las díadas. Los resultados sugieren que el apoyo de estructura y autonomía materno pudiera servir como acercamiento efectivo para conseguir y mantener la cooperación del niño durante negociaciones jerárquicas y que la mutualidad subóptima de la relación ensancha las respuestas de los niños pequeñitos a los niveles maternos de apoyo de autonomía. Las recomendaciones son probablemente relevantes para programas de crianza que llevan adelante el bienestar de la relación madre­niño durante la transición de la infancia a la niñez. Consistent with self­determination theory, maternal structuring and autonomy­supportive strategies made unique contributions to positively predicting toddler cooperation suggesting they may serve as effective and joint approaches for enlisting or maintaining cooperation during difficult request situations. As caregiver structuring is likely needed for many toddlers to accomplish multifaceted tasks, its positive association with cooperation was not altered by dyadic mutuality, an indicator of mother­child relationship history. Suboptimal relationship mutuality magnified the positive association between autonomy support and cooperation suggesting that mothers from dyads with low mutuality should be aware that their toddlers' cooperation may be especially sensitive to varying levels of autonomy support.

Changes in Breast Cancer Screening Prevalence in the US During the COVID-19 Pandemic, 2018-2022.

BACKGROUND: Annual mammography screening declined year-on-year during the COVID-19 pandemic through 2021. This study examined changes in 2022 compared to 2018 in the national prevalence of self-reported up-to-date mammography. METHODS: Using 2018-2022 data from the Center for Disease Control and Prevention's (CDC) Behavioral Risk Factor Surveillance System (BRFSS), we assess relative changes defined as annual prevalence ratios (aPR) in the SR receipt of past-year and up-to-date (UTD) breast cancer screening (bi-annual mammography in women ages 50-74 years) during the third year of the COVID-19 pandemic overall and by sociodemographic characteristics. RESULTS: UTD BC screening declined for the first time since 2018 (2018 compared to 2022, from 78.7% to 76.6%; aPR, 0.97; 95% CI, 0.96-0.98), despite a small increase in past-year breast cancer screening from 2020 and 2022 (57.9% to 59.6%; aPR, 1.03; 95% CI, 1.01-1.05). This translated to 747,791 fewer women reporting UTD with recommended BC screening in 2022 vs. 2018. UTD BC screening declines between 2018-2022 were largest for American Indian/Alaska Native women (74.8% to 62.2%; aPR, 0.83; 95% CI, 0.74-0.93), women with less formal educational attainment (< high school: 73.1% to 65.5%; aPR, 0.9; 95% CI, 0.85-0.95), and women without a usual source of care (48% to 42.9%; aPR, 0.85; 95% CI, 0.78-0.92). CONCLUSIONS: Previously noted pandemic-related declines in past-year BC screening now reflect in women reporting being UTD, with the largest declines in AI/AN and lower SES women. IMPACT: Future studies should monitor screening prevalence in relation to BC diagnostic stage, overall and by sociodemographic groups.

Improving long-term kidney allograft survival by rethinking HLA compatibility: from molecular matching to non-HLA genes.

Optimizing immunologic compatibility in organ transplantation extends beyond the conventional approach of Human Leukocyte Antigen (HLA) antigen matching, which exhibits significant limitations. A broader comprehension of the roles of classical and non-classical HLA genes in transplantation is imperative for enhancing long-term graft survival. High-resolution molecular HLA genotyping, despite its inherent challenges, has emerged as the cornerstone for precise patient-donor compatibility assessment. Leveraging understanding of eplet biology and indirect immune activation, eplet mismatch calculators and the PIRCHE-II algorithm surpass traditional methods in predicting allograft rejection. Understanding minor histocompatibility antigens may also present an opportunity to personalize the compatibility process. While the application of molecular matching in deceased donor organ allocation presents multiple technical, logistical, and conceptual barriers, rendering it premature for mainstream use, several other areas of donor-recipient matching and post-transplant management are ready to incorporate molecular matching. Provision of molecular mismatch scores to physicians during potential organ offer evaluations could potentially amplify long-term outcomes. The implementation of molecular matching in living organ donation and kidney paired exchange programs is similarly viable. This article will explore the current understanding of immunologic matching in transplantation and the potential applications of epitope and non-epitope molecular biology and genetics in clinical transplantation.

MAD-microbial (origin of) Alzheimer's disease hypothesis: from infection and the antimicrobial response to disruption of key copper-based systems.

Microbes have been suspected to cause Alzheimer's disease since at least 1908, but this has generally remained unpopular in comparison to the amyloid hypothesis and the dominance of Aß and Tau. However, evidence has been accumulating to suggest that these earlier theories are but a manifestation of a common cause that can trigger and interact with all the major molecular players recognized in AD. Aß, Tau and ApoE, in particular appear to be molecules with normal homeostatic functions but also with alternative antimicrobial functions. Their alternative functions confer the non-immune specialized neuron with some innate intracellular defenses that appear to be re-appropriated from their normal functions in times of need. Indeed, signs of infection of the neurons by biofilm-forming microbial colonies, in synergy with herpes viruses, are evident from the clinical and preclinical studies we discuss. Furthermore, we attempt to provide a mechanistic understanding of the AD landscape by discussing the antimicrobial effect of Aß, Tau and ApoE and Lactoferrin in AD, and a possible mechanistic link with deficiency of vital copper-based systems. In particular, we focus on mitochondrial oxidative respiration via complex 4 and ceruloplasmin for iron homeostasis, and how this is similar and possibly central to neurodegenerative diseases in general. In the case of AD, we provide evidence for the microbial Alzheimer's disease (MAD) theory, namely that AD could in fact be caused by a long-term microbial exposure or even long-term infection of the neurons themselves that results in a costly prolonged antimicrobial response that disrupts copper-based systems that govern neurotransmission, iron homeostasis and respiration. Finally, we discuss potential treatment modalities based on this holistic understanding of AD that incorporates the many separate and seemingly conflicting theories. If the MAD theory is correct, then the reduction of microbial exposure through use of broad antimicrobial and anti-inflammatory treatments could potentially alleviate AD although this requires further clinical investigation.

Patient preferences for ocular hypertension monitoring: a discrete choice experiment.

BACKGROUND/AIMS: To elicit the preferences and calculate the willingness to pay (WTP) of patients with ocular hypertension (OHT) for eye monitoring services in the UK. METHODS: Patients with OHT aged at least 18 years recruited from four NHS ophthalmology departments were included in the study. Patients' preferences and WTP for an OHT monitoring service in the National Health Service were elicited using a discrete choice experiment (DCE) within a postal survey based on six attributes: (1) how OHT monitoring is organised, (2) monitoring frequency, (3) travel time from home, (4) use of a risk calculator for conversion to glaucoma, (5) risk of developing glaucoma in the next 10 years and (6) cost of monitoring. We used a sequential mixed-methods approach to design the survey. RESULTS: 360 patients diagnosed with OHT were recruited with a mean age of 69 years. In the DCE, reducing the risk of conversion to glaucoma was the most important factor influencing respondents' choice of monitoring service. Respondents preferred hospital-based monitoring services to community optometrist monitoring, and annual monitoring compared with more frequent (every 6 months) and less frequent (every 18 or 24 months) monitoring. These results can be monetised using WTP. Results of heterogeneity analysis suggest that patients with prior experience in community optometrist monitoring preferred this to hospital-based monitoring. CONCLUSIONS: Although hospital-based monitoring is generally preferred, patients with prior experience in community services have a different opinion, suggesting that patients who are unfamiliar with community optometry services may need additional support to accept monitoring in this setting.

Enhanced microvascular imaging through deep learning-driven OCTA reconstruction with squeeze-and-excitation block integration.

Skin microvasculature is essential for cardiovascular health and thermoregulation in humans, yet its imaging and analysis pose significant challenges. Established methods, such as speckle decorrelation applied to optical coherence tomography (OCT) B-scans for OCT-angiography (OCTA), often require a high number of B-scans, leading to long acquisition times that are prone to motion artifacts. In our study, we propose a novel approach integrating a deep learning algorithm within our OCTA processing. By integrating a convolutional neural network with a squeeze-and-excitation block, we address these challenges in microvascular imaging. Our method enhances accuracy and reduces measurement time by efficiently utilizing local information. The Squeeze-and-Excitation block further improves stability and accuracy by dynamically recalibrating features, highlighting the advantages of deep learning in this domain.

Intraspecific venom variation in the medically important puff adder (Bitis arietans): Comparative venom gland transcriptomics, in vitro venom activity and immunological recognition by antivenom.

BACKGROUND: Variation in snake venoms is well documented, both between and within species, with intraspecific venom variation often correlated with geographically distinct populations. The puff adder, Bitis arietans, is widely distributed across sub-Saharan Africa and into the Arabian Peninsula where it is considered a leading cause of the ~310,000 annual snakebites across the region, with its venom capable of causing substantial morbidity and mortality. Despite its medical importance and wide geographic distribution, there is little known about venom variation between different B. arietans populations and the potential implications of this variation on antivenom efficacy. METHODOLOGY: We applied a range of analyses, including venom gland transcriptomics, in vitro enzymatic assays and reverse phase chromatography to comparatively analyse B. arietans venoms originating from Nigeria, Tanzania, and South Africa. Immunological assays and in vitro enzymatic neutralisation assays were then applied to investigate the impact of venom variation on the potential efficacy of three antivenom products; SAIMR Polyvalent, EchiTAb-Plus and Fav-Afrique. FINDINGS: Through the first comparison of venom gland transcriptomes of B. arietans from three geographically distinct regions (Nigeria, Tanzania, and South Africa), we identified substantial variation in toxin expression. Findings of venom variation were further supported by chromatographic venom profiling, and the application of enzymatic assays to quantify the activity of three pathologically relevant toxin families. However, the use of western blotting, ELISA, and in vitro enzymatic inhibition assays revealed that variation within B. arietans venom does not appear to substantially impact upon the efficacy of three African polyvalent antivenoms. CONCLUSIONS: The large distribution and medical importance of B. arietans makes this species ideal for understanding venom variation and the impact this has on therapeutic efficacy. The findings in this study highlight the likelihood for considerable venom toxin variation across the range of B. arietans, but that this may not dramatically impact upon the utility of treatment available in the region.

Regionalized cell and gene signatures govern esophageal epithelial homeostasis.

Regionalized disease prevalence is a common feature of the gastrointestinal tract. Herein, we employed regionally resolved Smart-seq3 single-cell sequencing, generating a comprehensive cell atlas of the adult mouse esophagus. Characterizing the esophageal axis, we identify non-uniform distribution of epithelial basal cells, fibroblasts, and immune cells. In addition, we demonstrate a position-dependent, but cell subpopulation-independent, transcriptional signature, collectively generating a regionalized esophageal landscape. Combining in vivo models with organoid co-cultures, we demonstrate that proximal and distal basal progenitor cell states are functionally distinct. We find that proximal fibroblasts are more permissive for organoid growth compared with distal fibroblasts and that the immune cell profile is regionalized in two dimensions, where proximal-distal and epithelial-stromal gradients impact epithelial maintenance. Finally, we predict and verify how WNT, BMP, insulin growth factor (IGF), and neuregulin (NRG) signaling are differentially engaged along the esophageal axis. We establish a cellular and transcriptional framework for understanding esophageal regionalization, providing a functional basis for epithelial disease susceptibility.

The Association between Sampling and Survival in Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy and Pancreaticoduodenectomy.

Adequate sampling is essential to an accurate pathologic evaluation of pancreatectomy specimens resected for pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT). However, limited data are available for the association between the sampling and survival in these patients. We examined the association of the entire submission of the tumor (ESOT) and the entire submission of the pancreas (ESOP) with disease-free survival (DFS) and overall survival (OS), as well as their correlations with clinicopathologic features, for 627 patients with PDAC who received NAT and pancreaticoduodenectomy. We demonstrated that both ESOT and ESOP were associated with lower ypT, less frequent perineural invasion, and better tumor response (p < 0.05). ESOP was also associated with a smaller tumor size (p < 0.001), more lymph nodes (p < 0.001), a lower ypN stage (p < 0.001), better differentiation (p = 0.02), and less frequent lymphovascular invasion (p = 0.009). However, since ESOP and ESOT were primarily conducted for cases with no grossly identifiable tumor or minimal residual carcinoma in initial sections, potential bias cannot be excluded. Both ESOT and ESOP were associated with less frequent recurrence/metastasis and better DFS and OS (p < 0.05) in the overall study population. ESOP was associated with better DFS and better OS in patients with ypT0/ypT1 or ypN0 tumors and better OS in patients with complete or near-complete response (p < 0.05). ESOT was associated with better OS in patients with ypT0/ypT1 or ypN0 tumors (p < 0.05). Both ESOT and ESOP were independent prognostic factors for OS according to multivariate survival analyses. Therefore, accurate pathologic evaluation using ESOP and ESOT is associated with the prognosis in PDAC patients with complete or near-complete pathologic response and ypT0/ypT1 tumor after NAT.

Molecular and Clinical Features of Pancreatic Acinar Cell Carcinoma: A Single-Institution Case Series.

Objectives: Acinar cell carcinoma (ACC) accounts for about 1% of pancreatic cancers. The molecular and clinical features of ACC are less characterized than those of pancreatic ductal adenocarcinoma. Methods: We retrospectively evaluated the clinical and molecular features of ACC patients who underwent germline and/or somatic molecular testing at The University of Texas MD Anderson Cancer Center from 2008 to 2022 and two cases from 2023-2024 who underwent RNA and TME analysis by Boston Gene. Patient information was extracted from our institutional database with the approval of the Institutional Review Board. Results: We identified 16 patients with available molecular testing results. Fourteen patients had metastatic disease, one had borderline resectable disease, and one had localized resectable disease at diagnosis. Fifteen patients were wild type for KRAS (one patient had unknown KRAS status). Somatic/germline mutations of DNA damage repair genes (BRCA1/2, PALB2, and ATM) were present in 5 of 12 patients tested for these genes. One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months. The median overall survival (OS) was 24 months for patients with metastatic disease. One of the additional two cases who underwent BostonGene testing was found to have NTRK1 fusion. RNA and TME analysis by Boston Gene of the two cases reported immune desert features and relatively lower RNA levels of CEACAM5, CD47, CD74, and MMP1 and higher RNA levels of CDH6 compared with PDAC.

Physical and mental health trajectories: A longitudinal SF-36 analysis in Alpha-1 antitrypsin deficiency-associated COPD.

BACKGROUND: The Short Form 36-Item Health Survey (SF-36) is a health-related quality of life (HRQoL) measure validated in people with chronic obstructive pulmonary disease (COPD). While physical health is often more impaired than mental health in people with COPD, research on alpha-1 antitrypsin deficiency (AATD)-associated COPD is limited. This longitudinal study examines changes in physical and mental health in individuals with AATD and associated factors. METHODS: Analyses included participants of AlphaNet, a disease management program for individuals with AATD-associated lung disease who are prescribed augmentation therapy. Norm-based SF-36 scores for mental and physical component summaries (MCS and PCS) and 8 scales were analyzed. Linear mixed models evaluated mean changes in SF-36 scores over time. RESULTS: The study included 2165 participants (mean age 56.9 ± 10.0 years, 47.0 % female). At enrollment, mean PCS score was 37.5 ± 9.6, and mean MCS score was 51.9 ± 10.5. Mean mMRC dyspnea score was 2.3 ± 1.3; 54.6 % had ≥2 exacerbations annually, and 46.5 % used oxygen regularly. Average follow-up was 6.6 ± 3.2 years. The HRQoL remained stable; MCS improved by 0.16 points/year (p < 0.0001), while the PCS score declined by 0.49 points/year (p < 0.0001). Subscales followed similar trends. CONCLUSIONS: At baseline, mental HRQoL scores were higher than physical HRQoL scores, indicating better mental health than physical health in this cohort with AATD-associated lung disease. Stable HRQoL with a slight improvement in mental scores over time and a small decrease in physical scores may be a unique feature of this cohort. Further studies are needed to correlate these findings with disease-specific instruments and patient physiology.

A Prospective, Randomized Trial of Bioresorbable Polymer Drug-Eluting Stents versus Fully Bioresorbable Scaffolds in Patients Undergoing Coronary Stenting.

Background: The performance of an everolimus-eluting bioresorbable scaffold (BRS) was inferior to an everolimus-eluting metallic drug-eluting stent (DES) with permanent polymer, mainly due the mechanical features of BRS technology. The performance of BRS as compared to metallic DES with bioresorbable polymers remains unstudied. Methods: This prospective, randomized, multicenter, clinical trial enrolled patients who underwent coronary stenting for de novo coronary lesions. Patients were randomly assigned to bioresorbable polymer everolimus-eluting stents (BP-EES) or everolimus-eluting BRS. The primary endpoint was percentage diameter stenosis (in-device) at 6- to 8-month angiographic surveillance. The main secondary endpoint was the device-oriented composite endpoint (DOCE) of cardiac death/target vessel-myocardial infarction/target lesion revascularization assessed after 12 months and 5 years. Results: The trial was prematurely terminated after the enrollment of 117 of 230 patients (BP-EES, n = 60; BRS, n = 57) due to safety issues associated with BRS technology. The primary endpoint of in-device diameter stenosis at angiographic surveillance was 12.5 ± 7.7% with BP-EES versus 19.3 ± 16.5% with BRS (p = 0.01). The DOCE occurred in 5.0% in the BP-EES group versus 12.3% of patients in the BRS group (hazard ratio [HR] 2.48, 95% confidence interval [CI] 0.64-9.58, p = 0.19) after 12 months and in 11.7% in the BP-EES group versus 26.4% of patients in the BRS group (HR 2.38, 95% CI 0.97-5.84, p = 0.06) after 5 years. Conclusions: BP-EES showed superior mid-term angiographic performance compared with BRS. Clinical event rates did not differ significantly between the groups up to 5 years of follow-up. These results should be interpreted with caution in view of the premature discontinuation of the study.

Androgen Society Position Paper on Cardiovascular Risk With Testosterone Therapy.

The Androgen Society is an international, multidisciplinary medical organization committed to advancing research and education in the field of testosterone deficiency and testosterone therapy (TTh). This position paper is written in response to results of the TRAVERSE study, published in June 2023, which reported no increased risk of major adverse cardiovascular events (MACE) in men who received TTh compared with placebo. In 2013-2014, 2 observational studies reported increased cardiovascular (CV) risks with TTh and received wide media attention. Despite strong criticism of those 2 studies, in 2015, the Food and Drug Administration added a CV warning to testosterone product labels and required pharmaceutical companies to perform a CV safety study, which became the TRAVERSE trial. TRAVERSE enrolled 5246 men at high risk for MACE based on existing heart disease or multiple risk factors. Participants were randomized to daily testosterone gel or placebo gel, with a mean follow-up of 33 months. Results revealed no greater risk of MACE (myocardial infarction, stroke, or CV death) or venothrombotic events in men who received TTh compared with placebo. Review of the prior literature reveals near uniformity of studies reporting no increased MACE with TTh. This includes 2 additional large randomized controlled trials, multiple smaller randomized controlled trials, several large observational studies, and 19 meta-analyses. In view of these findings, it is the position of the Androgen Society that it has now been conclusively determined that TTh is not associated with increased risks of heart attack, stroke, or CV death.

Lessons Learned from National Heart, Lung, and Blood Institute Covid-19 Clinical Trials.

AbstractIn response to the Covid-19 pandemic, the National Heart, Lung, and Blood Institute launched five multisite clinical trials testing candidate host tissue-directed medical interventions to hasten recovery, improve function, and reduce morbidity and mortality. Speed, flexibility, and collaboration were essential. This article from the Steering and Executive committees describes the Collaborating Network of Networks for Evaluating Covid-19 and Therapeutic Strategies (CONNECTS) research program that enrolled 6690 participants and evaluated 18 intervention strategies using 10 molecular agents across the care continuum (outpatient, inpatient, and post discharge), and reports lessons learned from this initiative. Successes include rapid trial execution through collaboration and adaptive platform designs. Challenges that impeded efficiency included time required to execute subcontracts, constraints on clinical research workforce, and limited research infrastructure in nonacademic settings.

Comparison of progression risk of monoclonal gammopathy of undetermined significance by method of detection.

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic pre-malignant disorder. The current standard of care is not to screen for MGUS, so it is often incidentally diagnosed in the clinic. It is unknown whether the outcomes of screened versus clinically detected MGUS differ. We compared the progression risk between screened versus clinical MGUS cohorts and assessed whether the MGUS detection method impacted risk prediction of established clinical factors (score). We included 379 screened MGUS from the Olmsted County population based study and 1384 MGUS patients diagnosed during routine clinical evaluation at Mayo Clinic. Median follow-up time for the screened versus clinical cohort was 26.6 and 40.1 years, respectively. Accounting for death as a competing risk, the cumulative incidence of progression at 25 years was similar in the screened (11.1% [95% CI 8.3-14.8]) versus clinical (10.1% [95% CI 8.6-11.8%]) MGUS cohorts, even when stratified by sex, age, or the baseline MGUS risk score. Overall, 0.9 (95% CI 0.6-1.2) screened versus 1.0 (95% CI 0.9-1.2) clinically detected MGUS patients experienced disease progression for every 100 person years of follow-up. MGUS detection method did not modify the association between MGUS risk score and progression risk (pinteraction=0.217) and did not add to known risk factors for progression (likelihood ratio test, p=0.839). Here we show that progression risk among patients with screened versus clinically detected heavy-chain MGUS was similar. Future studies are needed to assess if tailored follow-up of screened MGUS patients affects clinical outcomes.

The long-term effect of the coronavirus pandemic on parkrun participation: an interrupted time series analysis.

BACKGROUND: The growth of parkrun between 2004 and 2019 has been heralded as a success story for public health as a result of its physical activity and wellbeing benefits for participants. However, parkrun was not immune from the COVID-19 pandemic - with events in mainland England cancelled from March 2020 to July 2021. This study explores the lasting impact of the pandemic on parkrun participation to February 2023, and its implications across the socioeconomic spectrum. METHODS: The study combines aggregated parkrun weekly finisher data from 32,470 Lower Layer Super Output Areas (LSOA) in England from January 2015 to February 2023 with Office of National Statistics (ONS) data on population and deprivation. Interrupted time series analysis using segmented Poisson regression models was used to estimate the immediate change in parkrun participation and the change in the rate of growth following the pandemic. Models were fitted for each Index of Multiple Deprivation (IMD) quintile separately to assess whether this effect differed by socioeconomic deprivation. RESULTS: Visualisation and interrupted time series analysis showed a significant and long-term decrease in parkrun participation following the reopening of parkrun events. This was consistent across all IMD quintiles, indicating that the inequalities in parkrun participation according to IMD observed prior to the pandemic remained after the pandemic. Between March 2020 and February 2023, almost 13 million fewer parkrun finishes are estimated to have occurred relative to what would have occurred in the absence of the pandemic. CONCLUSION: The reduction in parkrun participation during the pandemic and following the reopening of events is likely to have negatively impacted wellbeing in would-be participants. Going forwards, policymakers must make the difficult trade-off between the long-term health and social implications of restricting outdoor physical activity events against the benefits associated with a reduction in infectious disease transmission.