Vertebral fractures and daily pain are associated with lower physical activity in postmenopausal women with back pain

Around 12% of women have vertebral fractures (VFs), and many of these individuals also have back pain which limits physical activity (PA). PA is important for health, but little is known about how VFs affect PA, and if so how this compares with individuals with back pain due to other causes. Therefore, we recruited 37 postmenopausal women from primary care with back pain, in whom the presence or absence of VFs was ascertained by spine radiographs. To provide an objective PA measure, vertical accelerations were recorded at 100 Hz for 7 days using a hip-worn GT3X+ accelerometer (Actigraph, USA). The number of low (0.5g-2g) was recorded. Participants also recorded their average back pain each day using a 10-point Likert scale. Linear mixed-effects models were used to assess group differences (fracture/nofracture cases) in low, medium and high-impact PA, and associations between daily pain and different PA impact levels. Daily PA and pain data had non-normal distributions and were log transformed. 12 women were found to have previously sustained VFs. These participants had lower levels of lowimpact PA (regression coefficient -0.64, 95%CI -1.03 to -0.25, P=0.002) but not medium or highimpact PA (both P>0.2). Across all participants, higher daily pain was associated with lower highimpact PA levels (-0.08, 95%CI -0.14 to -0.02, P=0.014) and weakly with medium–impact PA (-0.1, 95%CI -0.22 to 0.02, P=0.081) but not low-impact PA (P=0.25). These results suggest that VFs and daily pain are associated with lower levels of low and high-impact PA respectively, shown previously to differentially affect components of health. Low levels of low impact PA in women with VFs may impair weight control in these women. In contrast, reduced PA, in particular high-impact PA, in women with higher daily pain levels may increase the risk of sarcopenia and osteoporosis

Risk of SARS-CoV-2 reinfection during multiple Omicron variant waves in the UK general population

SARS-CoV-2 reinfections increased substantially after Omicron variants emerged. Large-scale community-based comparisons across multiple Omicron waves of reinfection characteristics, risk factors, and protection afforded by previous infection and vaccination, are limited. Here we studied ~45,000 reinfections from the UK’s national COVID-19 Infection Survey and quantified the risk of reinfection in multiple waves, including those driven by BA.1, BA.2, BA.4/5, and BQ.1/CH.1.1/XBB.1.5 variants. Reinfections were associated with lower viral load and lower percentages self-reporting symptoms compared with first infections. Across multiple Omicron waves, estimated protection against reinfection was significantly higher in those previously infected with more recent than earlier variants, even at the same time from previous infection. Estimated protection against Omicron reinfections decreased over time from the most recent infection if this was the previous or penultimate variant (generally within the preceding year). Those 14-180 days after receiving their most recent vaccination had a lower risk of reinfection than those >180 days from their most recent vaccination. Reinfection risk was independently higher in those aged 30-45 years, and with either low or high viral load in their most recent previous infection. Overall, the risk of Omicron reinfection is high, but with lower severity than first infections; both viral evolution and waning immunity are independently associated with reinfection

Daily Pain Severity but Not Vertebral Fractures Is Associated With Lower Physical Activity in Postmenopausal Women With Back Pain

Back pain lifetime incidence is 60%–70%, while 12%–20% of older women have vertebral fractures (VFs), often with back pain. We aimed to provide objective evidence, currently lacking, regarding whether back pain and VFs affect physical activity (PA). We recruited 69 women with recent back pain (age 74.5 ± 5.4 years). Low- (0.5  .11). VFs were not associated with PA (all p > .2). Higher daily pain levels but not VFs were associated with reduced low- and medium-impact PA, which could increase sarcopenia and falls risk in older women with back pain

Re-programming immunosurveillance in persistent non-infectious ocular inflammation

Ocular function depends on a high level of anatomical integrity. This is threatened by inflammation, which alters the local tissue over short and long time-scales. Uveitis due to autoimmune disease, especially when it involves the retina, leads to persistent changes in how the eye interacts with the immune system. The normal pattern of immune surveillance, which for immune privileged tissues is limited, is re-programmed. Many cell types, that are not usually present in the eye, become detectable. There are changes in the tissue homeostasis and integrity. In both human disease and mouse models, in the most extreme cases, immunopathological findings consistent with development of ectopic lymphoid-like structures and disrupted angiogenesis accompany severely impaired eye function. Understanding how the ocular environment is shaped by persistent inflammation is crucial to developing novel approaches to treatment

Re-programming immunosurveillance in persistent non-infectious ocular inflammation

Ocular function depends on a high level of anatomical integrity. This is threatened by inflammation, which alters the local tissue over short and long time-scales. Uveitis due to autoimmune disease, especially when it involves the retina, leads to persistent changes in how the eye interacts with the immune system. The normal pattern of immune surveillance, which for immune privileged tissues is limited, is re-programmed. Many cell types, that are not usually present in the eye, become detectable. There are changes in the tissue homeostasis and integrity. In both human disease and mouse models, in the most extreme cases, immunopathological findings consistent with development of ectopic lymphoid-like structures and disrupted angiogenesis accompany severely impaired eye function. Understanding how the ocular environment is shaped by persistent inflammation is crucial to developing novel approaches to treatment

A prospective cohort and extended comprehensive-cohort design provided insights about the generalizability of a pragmatic trial:the ProtecT prostate cancer trial

Objectives Randomized controlled trials (RCTs) deliver robust internally valid evidence but generalizability is often neglected. Design features built into the Prostate testing for cancer and Treatment (ProtecT) RCT of treatments for localized prostate cancer (PCa) provided insights into its generalizability. Study Design and Setting Population-based cluster randomization created a prospective study of prostate-specific antigen (PSA) testing and a comprehensive-cohort study including groups choosing treatment or excluded from the RCT, as well as those randomized. Baseline information assessed selection and response during RCT conduct. Results The prospective study (82,430 PSA-tested men) represented healthy men likely to respond to a screening invitation. The extended comprehensive cohort comprised 1,643 randomized, 997 choosing treatment, and 557 excluded with advanced cancer/comorbidities. Men choosing treatment were very similar to randomized men except for having more professional/managerial occupations. Excluded men were similar to the randomized socio-demographically but different clinically, representing less healthy men with more advanced PCa. Conclusion The design features of the ProtecT RCT provided data to assess the representativeness of the prospective cohort and generalizability of the findings of the RCT. Greater attention to collecting data at the design stage of pragmatic trials would better support later judgments by clinicians/policy-makers about the generalizability of RCT findings in clinical practice

Risk of SARS-CoV-2 reinfection during multiple Omicron variant waves in the UK general population

SARS-CoV-2 reinfections increased substantially after Omicron variants emerged. Large-scale community-based comparisons across multiple Omicron waves of reinfection characteristics, risk factors, and protection afforded by previous infection and vaccination, are limited. Here we studied ~45,000 reinfections from the UK’s national COVID-19 Infection Survey and quantified the risk of reinfection in multiple waves, including those driven by BA.1, BA.2, BA.4/5, and BQ.1/CH.1.1/XBB.1.5 variants. Reinfections were associated with lower viral load and lower percentages of self-reporting symptoms compared with first infections. Across multiple Omicron waves, estimated protection against reinfection was significantly higher in those previously infected with more recent than earlier variants, even at the same time from previous infection. Estimated protection against Omicron reinfections decreased over time from the most recent infection if this was the previous or penultimate variant (generally within the preceding year). Those 14–180 days after receiving their most recent vaccination had a lower risk of reinfection than those >180 days from their most recent vaccination. Reinfection risk was independently higher in those aged 30–45 years, and with either low or high viral load in their most recent previous infection. Overall, the risk of Omicron reinfection is high, but with lower severity than first infections; both viral evolution and waning immunity are independently associated with reinfection

Addition of symptoms to traditional risk factors improves prediction of those at high risk of vertebral fractures: Results of the Vfrac study

Less than a third of osteoporotic vertebral fractures (OVFs) come to clinical attention. This is due to a variety of reasons including inadequate understanding of the clinical triggers necessary to refer high risk individuals for spinal radiographs. Self-reported descriptions of back pain are increasingly recognised as useful clinical information. Purpose: To develop a simple clinical tool to help decide which older women with back pain should have a spinal radiograph, and to identify the additional clinical benefit of including self-reported back pain symptoms. Methods: 1634 women aged 65+ with back pain in the previous four months were recruited from primary care in the United Kingdom. Data were collected through self-completion questionnaires, physical examination and spinal radiographs. Exposure data included descriptions of back pain, traditional risk factors for osteoporosis, basic anthro-pometry and reported height loss. The outcome was the presence/absence of OVFs identified using the Algorithm-Based Qualitative method. Logistic regression models identified inde-pendent predictors of OVFs. AUC for the final model was calculated. AUC was recalculated after removal of self-reported pain descriptors, and compared to that for the final model. Proportions of those identified with OVFs with and without the use of back pain symptoms were identified. Results: Mean age was 73.9 years (range 65.4 to 96.8), and 209 (12.8%) had OVFs. The final Vfrac model comprised 15 independent predictors of OVF, with an AUC of 0.802 (95%CI 0.764-0.840). Removal of self-reported back pain symptoms reduced the AUC to 0.742 (95%CI 0.696-0.788). Without inclusion of back pain symptoms, the Vfrac tool identifies 66.5% of those with OVFs (53.7% with one and 92.5% with more than one). Adding back pain symptoms identifies 72.6% of those with OVFs (60.8% with one OVF and 96.1% with more than one). Sensitivity is increased from 66.5% to 72.5%. Conclusion: The Vfrac clinical tool appears valid and is improved by the addition of self-reported back pain symptoms. It now requires testing to establish real-world clinical and cost-effectiveness. Vfrac takes approximately 5 minutes to complete. The intention of Vfrac will be to help healthcare practitioners in primary care decide if an older woman with back pain is at high risk of an OVF and therefore requires a spinal radiograph to confirm the diagnosis

A novel pathogenic RBP-3 peptide reveals epitope spreading in persistent experimental autoimmune uveoretinitis

Experimental autoimmune uveoretinitis (EAU) in the C57BL/6J mouse is a model of non-infectious posterior segment intraocular inflammation that parallels clinical features of the human disease. The purpose of this study was to analyse the immune response to the four murine subunits of retinol binding protein-3 (RBP-3) to identify pathogenic epitopes to investigate the presence of intramolecular epitope spreading during the persistent inflammation phase observed in this model of EAU. Recombinant murine subunits of the RBP-3 protein were purified and used to immunize C57BL/6J mice to induce EAU. An overlapping peptide library was used to screen RBP-3 subunit 3 for immunogenicity and pathogenicity. Disease phenotype and characterization of pathogenic subunits and peptides was undertaken by topical endoscopic fundal imaging, immunohistochemistry, proliferation assays and flow cytometry. RBP-3 subunits 1, 2 and 3 induced EAU in the C57BL/6J mice, with subunit 3 eliciting the most destructive clinical disease. Within subunit 3 we identified a novel uveitogenic epitope, 629–643. The disease induced by this peptide was comparable to that produced by the uveitogenic 1–20 peptide. Following immunization, peptide-specific responses by CD4(+) and CD8(+) T-cell subsets were detected, and cells from both populations were present in the retinal inflammatory infiltrate. Intramolecular epitope spreading between 629–643 and 1–20 was detected in mice with clinical signs of disease. The 629–643 RBP-3 peptide is a major uveitogenic peptide for the induction of EAU in C57BL/6J mice and the persistent clinical disease induced with one peptide leads to epitope spreading