How well can we measure chronic pain impact in existing longitudinal cohort studies? Lessons learned.

Multiple large longitudinal cohorts provide opportunities to address questions about predictors of pain and pain trajectories, even when not anticipated in design of the historical databases. This focus article uses two empirical examples to illustrate the processes of assessing the measurement properties of data from large cohort studies to answer questions about pain. In both examples, data were screened to select candidate variables that captured the impact of chronic pain on self-care activities, productivity and social activities. We describe a series of steps to select candidate items and evaluate their psychometric characteristics in relation to the measurement of pain impact proposed. In UK Biobank, a general lack of internal consistency of variables selected prevented the identification of a satisfactory measurement model, with lessons for the measurement of chronic pain impact. In the English Longitudinal Study of Ageing, a measurement model for chronic pain impact was identified, albeit limited to capturing the impact of pain on self-care and productivity but lacking coverage related to social participation. In conjunction with its supplementary material, this focus article aims to encourage exploration of these valuable prospectively collected data; to support researchers to make explicit the relationships between items in the databases and constructs of interest in pain research; and to use empirical methods to estimate the possible biases in these variables. PERSPECTIVE: This focus article outlines a theory-driven approach for fitting new measurement models to data from large cohort studies, and evaluating their psychometric properties. This aims to help researchers develop an empirical understanding of the gains and limitations connected with the process of re-purposing the data stored in these datasets.

The effect of proximity to grocery stores and the pandemic on parents' and youths' perceptions of eating habits in predominately African American rural communities.

Background: Rural communities have a disproportionately high level of childhood obesity along with high rates of food insecurity. Objectives: To assess the eating habits of youth in predominantly African American rural communities and assess the association between proximity to a grocery store and eating habits as well as how the COVID-19 pandemic may have impacted eating habits. Methods: 203 youth and parents completed a 16-item survey. Analyses were performed to assess the effect of having a neighborhood grocery store as well as to compare responses between youth and parents. Results: Having a neighborhood grocery store was associated with increased consumption of vegetables (F(1,122) = 41.56) and fruits (F(1,121) = 65.05), decreased consumption of chips (F(1,125) = 79.51) and a smaller percentage of overweight youth (χ2(1,125) = 5.03). Parents underestimated the effect of the COVID-19 pandemic on youth eating habits (χ2 (1,198) = 17.88). Conclusion: Proximity to a grocery store significantly associated with eating habits and weight in the rural communities examined. Given the steady decrease in the number rural grocery stores over the past decade it is important to consider how to improve access to healthy foods in these communities.

Pediatric sport and nonsport concussions presenting to emergency departments: injury circumstances, characteristics, and clinical management.

OBJECTIVE: The aim of this study was to compare injury circumstances, characteristics, and clinical management of emergency department (ED) presentations for sports-related concussion (SRC) and non-SRC. METHODS: This multicenter prospective observational study identified patients 5-17 years old who presented to EDs within 24 hours of head injury, with one or more signs or symptoms of concussion. Participants had a Glasgow Coma Scale score of 13-15 and no abnormalities on CT (if performed). Data were stratified by age: young children (5-8 years), older children (9-12 years), and adolescents (13-17 years). RESULTS: Of 4709 patients meeting the concussion criteria, non-SRC accounted for 56.3% of overall concussions, including 80.9% of younger child, 51.1% of older child, and 37.0% of adolescent concussions. The most common mechanism of non-SRC was falls for all ages. The most common activity accounting for SRC was bike riding for younger children, and rugby for older children and adolescents. Concussions occurring in sports areas, home, and educational settings accounted for 26.2%, 21.8%, and 19.0% of overall concussions. Concussions occurring in a sports area increased with age, while occurrences in home and educational settings decreased with age. The presence of amnesia significantly differed for SRC and non-SRC for all age groups, while vomiting and disorientation differed for older children and adolescents. Adolescents with non-SRC were admitted to a ward and underwent CT at higher proportions than those with SRC. CONCLUSIONS: Non-SRC more commonly presented to EDs overall, with SRC more common with increasing age. These data provide important information to inform public health policies, guidelines, and prevention efforts.

Lymphotoxin ß receptor and tertiary lymphoid organs shape acute and chronic allograft rejection.

Solid organ transplantation remains the life-saving treatment for end-stage organ failure, but chronic rejection remains a major obstacle to long-term allograft outcomes and has not improved substantially. Tertiary lymphoid organs (TLOs) are ectopic lymphoid structures that form under conditions of chronic inflammation, and evidence from human transplantation suggests that TLOs regularly form in allografts undergoing chronic rejection. In this study, we utilized a mouse renal transplantation model and manipulation of the lymphotoxin αß/lymphotoxin ß receptor (LTαß/LTßR) pathway, which is essential for TLO formation, to define the role of TLOs in transplantation. We showed that intragraft TLOs are sufficient to activate the alloimmune response and mediate graft rejection in a model where the only lymphoid organs are TLOs in the allograft. When transplanted to recipients with a normal set of secondary lymphoid organs, the presence of graft TLOs or LTα overexpression accelerated rejection. If the LTßR pathway was disrupted in the donor graft, TLO formation was abrogated, and graft survival was prolonged. Intravital microscopy of renal TLOs demonstrated that local T and B cell activation in TLOs is similar to that observed in secondary lymphoid organs. In summary, we demonstrated that immune activation in TLOs contributes to local immune responses, leading to earlier allograft failure. TLOs and the LTαß/LTßR pathway are therefore prime targets to limit local immune responses and prevent allograft rejection. These findings are applicable to other diseases, such as autoimmune diseases or tumors, where either limiting or boosting local immune responses is beneficial and improves disease outcomes.

Mental health and conflict: a pilot of an online eye movement desensitisation and reprocessing (EMDR) intervention for forcibly displaced Syrian women.

Background: The Syrian conflict has been ongoing since 2011. Practical and scalable solutions are urgently needed to meet an increase in need for specialised psychological support for post-traumatic stress disorder given limited availability of clinicians. Training forcibly displaced Syrians with a mental health background to remotely deliver specialised interventions increases the availability of evidence based psychological support. Little is known about the effectiveness of online therapy for forcibly displaced Syrian women provided by forcibly displaced Syrian women therapists. Purpose: To pilot an evidence-based trauma therapy, Eye Movement Desensitisation and Reprocessing (EMDR), carried out online by trained forcibly displaced Syrian women therapists for forcibly displaced Syrian women who require treatment for post-traumatic stress disorder (PTSD). Methods: 83 forcibly displaced Syrian women, living in Türkiye or inside Syria, with diagnosable PTSD, were offered up to 12 sessions of online EMDR over a period of 3 months. This was delivered by forcibly displaced Syrian women therapists who were trained in EMDR. Data were gathered, using Arabic versions, on PTSD symptoms using the Impact of Events Scale Revised, depression symptoms using the Patient Health Questionnaire-9 and anxiety symptoms using the Generalised Anxiety Disorder Assessment-7 at baseline, mid-point, and end of therapy. Results: PTSD scores, depression scores and anxiety scores all significantly reduced over the course of treatment, with lower scores at midpoint than baseline and lower scores at end of treatment than at midpoint. Only one participant (1%) exceeded the cutoff point for PTSD, and 13 (16%) exceeded the cutoff points for anxiety and depression at the end of treatment. Conclusion: In this pilot study up to 12 sessions of online EMDR were associated with reductions in PTSD, anxiety and depression symptoms in Syrian women affected by the Syrian conflict. The training of forcibly displaced Syrian mental health professionals to deliver online therapy is a relatively low cost, scalable, sustainable solution to ensure that those who are affected by the conflict can access specialised support. Further research is needed using a control group to confirm that the observed effects are due to EMDR treatment, as is research with post-treatment follow-up to ascertain that benefits are maintained.

Pain and other complications of pelvic mesh: a systematic review of qualitative studies and thematic synthesis of women's accounts.

OBJECTIVES: Synthesis of the experience of women with pain from pelvic or vaginal mesh or its removal, to identify pain-related problems and to formulate psychological aspects of pain. DESIGN: Systematic review and thematic analysis of qualitative studies of pain from pelvic or vaginal mesh, or mesh removal, in women over 18 years, using individual interviews, focus groups, free text, or written or oral contributions to formal enquiries. DATA SOURCES: Medline, Embase and PsycINFO, from inception to 26 April 2023. ELIGIBILITY CRITERIA: Qualitative studies of pain and other symptoms from pelvic or vaginal mesh or its removal; adults; no language restriction. DATA EXTRACTION AND SYNTHESIS: Line-by-line coding of participant quotations and study author statements by one author to provide codes that were applied to half the studies by another author and differences resolved by discussion. Codes were grouped into subthemes and themes by both authors, then scrutinised and discussed by a focus group of mesh-injured women for omissions, emphasis and coherence. Studies were appraised using an amalgamation of the CASP and COREQ tools. RESULTS: 2292 search results produced 9 eligible studies, with 7-752 participants, a total of around 2000. Four recruited patients, four totally or partially from mesh advocacy groups, and two were national enquiries (UK and Australia). Four major themes were as follows: broken body, broken mind; distrust of doctors and the medical industry; broken life and keeping going-a changed future. Psychological content mainly concerned the loss of trust in medical care, leaving women unsupported in facing an uncertain future. Mesh-injured women strongly endorsed the findings. CONCLUSIONS: Pain and other problems associated with pelvic mesh are profound and far-reaching for women affected. Worse, they feel subject to continued gaslighting, including denial of their mesh-related problems and dismissal of their concerns about continued mesh insertion. PROSPERO REGISTRATION NUMBER: CRD42022330527.

Making sense of pain in inflammatory bowel disease (IBD): A qualitative study.

OBJECTIVES: Inflammatory bowel disease (IBD) is a chronic, gastrointestinal tract condition, in which pain is one of the most widespread and debilitating symptoms, yet research about how individuals make sense of their IBD pain is lacking. The current study aimed to explore how individuals with IBD understand their pain. METHODS: Twenty participants, recruited via the Crohn's & Colitis UK charity, were interviewed about their understanding of their IBD pain using the Grid Elaboration Method that elicits free associations on which it invites elaboration. Thematic analysis was used to organise transcribed verbatim data. RESULTS: Three related themes - making sense of my pain, navigating my care and support and it takes its toll - comprising seven sub-themes, illustrated the ways in which participants made sense of pain experientially, multi-dimensionally, and in the broader context of IBD and its symptoms. The psychological impact of pain was evident across all interviews. CONCLUSIONS: The findings are consistent with other research in IBD pain, demonstrating the importance of pain in IBD. Sense-making underpins both emotional and practical responses to pain and ideally is constructed as an integral part of clinical care of IBD.

A Qualitative Evaluation of the Acceptability of Shigellosis Prevention Recommendations Among Gay, Bisexual, and Other Men Who Have Sex With Men.

BACKGROUND: Shigellosis is diarrheal disease caused by highly infectious Shigella bacteria. Shigella can spread in multiple ways, including sexual contact. Gay, bisexual, and other men who have sex with men are particularly at risk for shigellosis. METHODS: To evaluate the acceptability of 3 Centers for Disease Control and Prevention-developed behavioral recommendations for the prevention of sexually transmitted shigellosis, virtual in-depth interviews were conducted among 26 gay or bisexual men in March to May 2021. RESULTS: Participants had a median age of 25 years; 65% were non-Hispanic White, 12% were Hispanic White, 12% Asian, 4% Hispanic Black, and 8% multiracial/other. Respondents indicated willingness to engage in certain prevention behaviors (e.g., washing hands, genitals, and anus before and after sex), but were less willing to engage in behaviors that were viewed as outside social norms or difficult to practice (e.g., dental dams for oral-anal contact; latex gloves for fingering or fisting). Respondents thought recommendations may be more feasible if knowledge of shigellosis was greater; however, some perceived that the severity of shigellosis is low and did not warrant the effort of engaging in prevention behaviors. CONCLUSIONS: Educational efforts to increase awareness of shigellosis and other enteric diseases spread through sexual contact are needed and public health practitioners should consider the acceptability of how realistic it is for individuals to engage in certain prevention behaviors. Rather than recommending behaviors that do not have buy-in, it may be more efficacious to focus recommendations on adopting behaviors reported as acceptable to the target audience.

Correction: Linking bacterial enterotoxins and alpha defensin 5 expansion in the Crohn's colitis: A new insight into the etiopathogenetic and differentiation triggers driving colonic inflammatory bowel disease.

[This corrects the article DOI: 10.1371/journal.pone.0246393.].

Evaluation of enzyme activity predictions for variants of unknown significance in Arylsulfatase A.

Continued advances in variant effect prediction are necessary to demonstrate the ability of machine learning methods to accurately determine the clinical impact of variants of unknown significance (VUS). Towards this goal, the ARSA Critical Assessment of Genome Interpretation (CAGI) challenge was designed to characterize progress by utilizing 219 experimentally assayed missense VUS in the Arylsulfatase A (ARSA) gene to assess the performance of community-submitted predictions of variant functional effects. The challenge involved 15 teams, and evaluated additional predictions from established and recently released models. Notably, a model developed by participants of a genetics and coding bootcamp, trained with standard machine-learning tools in Python, demonstrated superior performance among submissions. Furthermore, the study observed that state-of-the-art deep learning methods provided small but statistically significant improvement in predictive performance compared to less elaborate techniques. These findings underscore the utility of variant effect prediction, and the potential for models trained with modest resources to accurately classify VUS in genetic and clinical research.

Multiomics data integration, limitations, and prospects to reveal the metabolic activity of the coral holobiont.

Since their radiation in the Middle Triassic period ∼240 million years ago, stony corals have survived past climate fluctuations and five mass extinctions. Their long-term survival underscores the inherent resilience of corals, particularly when considering the nutrient-poor marine environments in which they have thrived. However, coral bleaching has emerged as a global threat to coral survival, requiring rapid advancements in coral research to understand holobiont stress responses and allow for interventions before extensive bleaching occurs. This review encompasses the potential, as well as the limits, of multiomics data applications when applied to the coral holobiont. Synopses for how different omics tools have been applied to date and their current restrictions are discussed, in addition to ways these restrictions may be overcome, such as recruiting new technology to studies, utilizing novel bioinformatics approaches, and generally integrating omics data. Lastly, this review presents considerations for the design of holobiont multiomics studies to support lab-to-field advancements of coral stress marker monitoring systems. Although much of the bleaching mechanism has eluded investigation to date, multiomic studies have already produced key findings regarding the holobiont's stress response, and have the potential to advance the field further.

Reframing pain: the power of individual and societal factors to enhance pain treatment.

The effectiveness of analgesics can be increased if synergistic behavioural, psychological, and pharmacological interventions are provided within a supportive environment.

Appraisal of Australian and New Zealand paediatric sepsis guidelines.

OBJECTIVE: Clinical practice guidelines (CPGs) are an important tool for the management of children with sepsis. The quality, consistency and concordance of Australian and New Zealand (ANZ) childhood sepsis CPGs with the Australian Commission on Safety and Quality in Healthcare (ACSQHC) sepsis clinical care standards and international sepsis guidelines is unclear. METHODS: We accessed childhood sepsis CPGs for all ANZ states and territories through Paediatric Research in Emergency Departments International Collaborative members. The guidelines were assessed for quality using the AGREE-II instrument. Consistency between CPG treatment recommendations was assessed, as was concordance with the ACSQHC sepsis clinical care standards and international sepsis guidelines. RESULTS: Overall, eight CPGs were identified and assessed. CPGs used a narrative and pathway format, with those using both having the highest quality overall. CPG quality was highest for description of scope and clarity of presentation, and lowest for editorial independence. Consistency between guidelines for initial treatment recommendations was poor, with substantial variation in the choice and urgency of empiric antimicrobial administration; the choice, volume and urgency of fluid resuscitation; and the choice of first-line vasoactive agent. Most CPGs were concordant with time-critical components of the ACSQHC sepsis clinical care standard, although few addressed post-acute care. Concordance with international sepsis guidelines was poor. CONCLUSION: Childhood sepsis CPGs in current use in ANZ are of variable quality and lack consistency with key treatment recommendations. CPGs are concordant with the ACSQHC care standard, but not with international sepsis guidelines. A bi-national sepsis CPG may reduce unnecessary variation in care.

Identification of SARS-CoV-2 variants in indoor dust.

Environmental surveillance of pathogens underlying infectious disease is critical to ensure public health. Recent efforts to track SARS-CoV-2 have utilized wastewater sampling to infer community trends in viral abundance and variant composition. Indoor dust has also been used for building-level inferences, though to date no sequencing data providing variant-scale resolution have been reported from dust samples, and strategies to monitor circulating variants in dust are needed to help inform public health decisions. In this study, we demonstrate that SARS-CoV-2 lineages can be detected and sequenced from indoor bulk dust samples. We collected 93 vacuum bags from April 2021 to March 2022 from buildings on The Ohio State University's (OSU) Columbus campus, and the dust was used to develop and apply an amplicon-based whole-genome sequencing protocol to identify the variants present and estimate their relative abundances. Three variants of concern were detected in the dust: Alpha, Delta, and Omicron. Alpha was found in our earliest sample in April 2021 with an estimated frequency of 100%. Delta was the primary variant present from October of 2021 to January 2022, with an average estimated frequency of 91% (±1.3%). Omicron became the primary variant in January 2022 and was the dominant strain in circulation through March with an estimated frequency of 87% (±3.2%). The detection of these variants on OSU's campus correlates with the circulation of these variants in the surrounding population (Delta p<0.0001 and Omicron p = 0.02). Overall, these results support the hypothesis that dust can be used to track COVID-19 variants in buildings.

Cost-effectiveness of intervention combinations towards the elimination of vertical transmission of HIV in limited-resource settings: a mathematical modelling study.

BACKGROUND: Since 2000, there has been a substantial global reduction in the vertical transmission of HIV. Despite effective interventions, gaps still remain in progress towards elimination in many low-income and middle-income countries. We developed a mathematical model to determine the most cost-effective combinations of interventions to prevent vertical transmission. METHODS: We developed a 12-month Markov model to follow a cohort of women of childbearing age (aged 15-49 years) in Zambia (n=1 107 255) who were either pregnant, in delivery, or breastfeeding; the population included in the model reflects the estimated number of pregnant women in Zambia from the 2018 Zambia Demographic and Health Survey. The model incorporated nine interventions: infant prophylaxis; three different HIV retesting schedule options; oral pre-exposure prophylaxis; maternal peer-support groups; regimen shift; tracing of loss to follow-up; and point-of-care viral load testing. We analysed incident HIV infections among mothers and infants, intervention costs, and evaluated 190 scenarios of different combinations of inventions to calculate the incremental cost-effectiveness ratios (ICERs) over 1 year. FINDINGS: Three interventions with the greatest reduction in vertical transmission, individually, were support groups for 80% of those in need (35% reduction in infant infections), HIV retesting schedules (6·5% reduction), and infant prophylaxis (4·5% reduction). Of all 190 scenarios evaluated, eight were on the cost-effectiveness frontier (ie, were considered to be cost-effective); all eight included increasing infant prophylaxis, regimen shift, and use of support groups. Excluding the highest-cost scenarios, for a 1-22% increase in total budget, 23-43% of infant infections could be prevented, producing ICERs between US$244 and $16 242. INTERPRETATION: Using the interventions modelled, it is possible to reduce vertical transmission and to cost-effectively prevent up to 1734 infant HIV infections (43% reduction) in Zambia over a period of 1 year. To optimise their effect, these interventions must be scaled with fidelity. Future work is needed to incorporate evidence on additional innovative interventions and HIV risk factors, and to apply the model to other country contexts to support targeted implementation and resource use. FUNDING: The ELMA Foundation.

Sepsis epidemiology in Australian and New Zealand children (SENTINEL): protocol for a multicountry prospective observational study.

INTRODUCTION: Sepsis affects 25.2 million children per year globally and causes 3.4 million deaths, with an annual cost of hospitalisation in the USA of US$7.3 billion. Despite being common, severe and expensive, therapies and outcomes from sepsis have not substantially changed in decades. Variable case definitions, lack of a reference standard for diagnosis and broad spectrum of disease hamper efforts to evaluate therapies that may improve sepsis outcomes. This landscape analysis of community-acquired childhood sepsis in Australia and New Zealand will characterise the burden of disease, including incidence, severity, outcomes and cost. Sepsis diagnostic criteria and risk stratification tools will be prospectively evaluated. Sepsis therapies, quality of care, parental awareness and understanding of sepsis and parent-reported outcome measures will be described. Understanding these aspects of sepsis care is fundamental for the design and conduct of interventional trials to improve childhood sepsis outcomes. METHODS AND ANALYSIS: This prospective observational study will include children up to 18 years of age presenting to 12 emergency departments with suspected sepsis within the Paediatric Research in Emergency Departments International Collaborative network in Australia and New Zealand. Presenting characteristics, management and outcomes will be collected. These will include vital signs, serum biomarkers, clinician assessment of severity of disease, intravenous fluid administration for the first 24 hours of hospitalisation, organ support therapies delivered, antimicrobial use, microbiological diagnoses, hospital and intensive care unit length-of-stay, mortality censored at hospital discharge or 30 days from enrolment (whichever comes first) and parent-reported outcomes 90 days from enrolment. We will use these data to determine sepsis epidemiology based on existing and novel diagnostic criteria. We will also validate existing and novel sepsis risk stratification criteria, characterise antimicrobial stewardship, guideline adherence, cost and report parental awareness and understanding of sepsis and parent-reported outcome measures. ETHICS AND DISSEMINATION: Ethics approval was received from the Royal Children's Hospital of Melbourne, Australia Human Research Ethics Committee (HREC/69948/RCHM-2021). This included incorporated informed consent for follow-up. The findings will be disseminated in a peer-reviewed journal and at academic conferences. TRIAL REGISTRATION NUMBER: ACTRN12621000920897; Pre-results.

Predicting the impact of rare variants on RNA splicing in CAGI6.

Variants which disrupt splicing are a frequent cause of rare disease that have been under-ascertained clinically. Accurate and efficient methods to predict a variant's impact on splicing are needed to interpret the growing number of variants of unknown significance (VUS) identified by exome and genome sequencing. Here, we present the results of the CAGI6 Splicing VUS challenge, which invited predictions of the splicing impact of 56 variants ascertained clinically and functionally validated to determine splicing impact. The performance of 12 prediction methods, along with SpliceAI and CADD, was compared on the 56 functionally validated variants. The maximum accuracy achieved was 82% from two different approaches, one weighting SpliceAI scores by minor allele frequency, and one applying the recently published Splicing Prediction Pipeline (SPiP). SPiP performed optimally in terms of sensitivity, while an ensemble method combining multiple prediction tools and information from databases exceeded all others for specificity. Several challenge methods equalled or exceeded the performance of SpliceAI, with ultimate choice of prediction method likely to depend on experimental or clinical aims. One quarter of the variants were incorrectly predicted by at least 50% of the methods, highlighting the need for further improvements to splicing prediction methods for successful clinical application.

Sensing behavior change in chronic pain: a scoping review of sensor technology for use in daily life.

ABSTRACT: Technology offers possibilities for quantification of behaviors and physiological changes of relevance to chronic pain, using wearable sensors and devices suitable for data collection in daily life contexts. We conducted a scoping review of wearable and passive sensor technologies that sample data of psychological interest in chronic pain, including in social situations. Sixty articles met our criteria from the 2783 citations retrieved from searching. Three-quarters of recruited people were with chronic pain, mostly musculoskeletal, and the remainder with acute or episodic pain; those with chronic pain had a mean age of 43 (few studies sampled adolescents or children) and 60% were women. Thirty-seven studies were performed in laboratory or clinical settings and the remainder in daily life settings. Most used only 1 type of technology, with 76 sensor types overall. The commonest was accelerometry (mainly used in daily life contexts), followed by motion capture (mainly in laboratory settings), with a smaller number collecting autonomic activity, vocal signals, or brain activity. Subjective self-report provided "ground truth" for pain, mood, and other variables, but often at a different timescale from the automatically collected data, and many studies reported weak relationships between technological data and relevant psychological constructs, for instance, between fear of movement and muscle activity. There was relatively little discussion of practical issues: frequency of sampling, missing data for human or technological reasons, and the users' experience, particularly when users did not receive data in any form. We conclude the review with some suggestions for content and process of future studies in this field.