Putting computational models of immunity to the test - an invited challenge to predict B. pertussis vaccination outcomes.

Systems vaccinology studies have been used to build computational models that predict individual vaccine responses and identify the factors contributing to differences in outcome. Comparing such models is challenging due to variability in study designs. To address this, we established a community resource to compare models predicting B. pertussis booster responses and generate experimental data for the explicit purpose of model evaluation. We here describe our second computational prediction challenge using this resource, where we benchmarked 49 algorithms from 53 scientists. We found that the most successful models stood out in their handling of nonlinearities, reducing large feature sets to representative subsets, and advanced data preprocessing. In contrast, we found that models adopted from literature that were developed to predict vaccine antibody responses in other settings performed poorly, reinforcing the need for purpose-built models. Overall, this demonstrates the value of purpose-generated datasets for rigorous and open model evaluations to identify features that improve the reliability and applicability of computational models in vaccine response prediction.

Standardized Temporary Atrial Epicardial Wire Locations Lead to Enhanced Atrial Signal Identification.

Background: Arrhythmias, common after pediatric cardiac surgery, are associated with increased morbidity and mortality. Atrial epicardial wires (AEW) improve diagnostic accuracy but have variable pacing and sensing properties based on their location. Even so, there are no longitudinal prospective pediatric studies examining ideal placement of AEW. Methods: This multicenter study compared atrial amplitudes, pacing sensitivities and thresholds via AEW placed at Bachmann's Bundle (BB) and the interatrial groove near the right pulmonary veins (IGRPV) versus the surgeons' standard locations. An AtriAmp system was used to obtain an atrial ECG to calculate atrial and ventricular amplitude from atrial electrograms on the bedside monitor. Sensitivities and thresholds via a temporary pacemaker were documented. ANOVA tests with repeated measures and post-hoc pairwise comparisons were performed to compare variables within the first 24-h postoperative hours. Mixed effects linear regression models were employed to examine daily trends. Results: In the first 24-h following cardiac surgery, AEW at BB and IGRPV showed significantly larger atrial amplitudes than the surgeons' standard locations. In addition, there was a negative trend in atrial ECG amplitude in all AEW from postoperative days 0 to 1; however, subsequent days showed a positive mean change in atrial amplitude with largest increase seen at BB. Atrial sensing as measured by the temporary pacemaker had statistically greater atrial signal amplitude from the BB-IGRPV set in both polarities (ie, with the BB as the - or + electrode pair) as compared to the surgeons' standard locations. No difference in atrial thresholds (mA) were noted in the immediate postoperative period or over time, with a relatively low atrial threshold at all sites. Conclusion: Standardization of AEW at Bachmann's Bundle can yield largest atrial amplitudes by atrial ECG and highest atrial sensing parameters without compromising atrial thresholds.

Maintenance of thermogenic adipose tissues despite loss of the H3K27 acetyltransferases p300 or CBP.

Brown and beige adipose tissues are specialized for thermogenesis and are important for energy balance in mice. Mounting evidence suggests that chromatin-modifying enzymes are integral for the development, maintenance, and functioning of thermogenic adipocytes. p300 and cAMP-response element binding protein (CREB)-binding protein (CBP) are histone acetyltransferases (HATs) responsible for writing the transcriptionally activating mark H3K27ac. Despite their homology, p300 and CBP do have unique tissue- and context-dependent roles, which have yet to be examined in brown and beige adipocytes specifically. We assessed the requirement of p300 or CBP in thermogenic fat using uncoupling protein 1 (Ucp1)-Cre-mediated knockdown in mice to determine whether their loss impacted tissue development, susceptibility to diet-induced obesity, and response to pharmacological induction via ß3-agonism. Despite successful knockdown, brown adipose tissue mass and expression of thermogenic markers were unaffected by loss of either HAT. As such, knockout mice developed a comparable degree of diet-induced obesity and glucose intolerance to that of floxed controls. Furthermore, "browning" of white adipose tissue by the ß3-adrenergic agonist CL-316,243 remained largely intact in knockout mice. Although p300 and CBP have nonoverlapping roles in other tissues, our results indicate that they are individually dispensable within thermogenic fats specifically, possibly due to functional compensation by one another.NEW & NOTEWORTHY The role of transcriptionally activating H3K27ac epigenetic mark has yet to be examined in mouse thermogenic fats specifically, which we achieved here via Ucp1-Cre-driven knockdown of the histone acetyltransferases (HAT) p300 or CBP under several metabolic contexts. Despite successful knockdown of either HAT, brown adipose tissue was maintained at room temperature. As such, knockout mice were indistinguishable to controls when fed an obesogenic diet or when given a ß3-adrenergic receptor agonist to induce browning of white fat. Unlike other tissues, thermogenic fats are resilient to p300 or CBP ablation, likely due to sufficient functional overlap between them.

Body image at the trunk: An investigation into externally referenced width perception and picture mapping.

Body image is a conscious representation of the body, encompassing how our body feels to us. Body image can be measured in a variety of ways, including metric and depictive measures. This study sought to assess body image at the trunk by investigating, and comparing, a metric and depictive measure. Sixty-nine healthy participants estimated their thorax, waist, and hip width by externally referencing mechanical calipers. Participants were also asked to select the true image of their trunk from a random display of nine images containing the true image and incrementally shrunken or enlarged images. Participants demonstrated evidence of thorax and waist width overestimation in the width perception task, with no evidence for hip misestimation. For the picture mapping task, the majority of participants were inaccurate. In participants who were inaccurate, approximately equal proportions underestimated and overestimated their trunk width. The two tasks were found to be independent of each other. Distortions, or inaccuracies, were apparent in a metric measure, and inaccuracies also present in a depictive measure, of body image at the trunk for healthy participants. An overestimation bias was apparent in the metric, but not depictive, task. No relationship was found between tasks..

A protocol for the co-creation and usability/acceptability testing of an evidence-based, patient-centred intervention for self-management of urinary incontinence in older men.

Male urinary incontinence (UI) is most prevalent in older men, with one in three men aged 65 and above having problems maintaining continence. Addressing health inequalities, male-female disparities in continence services, and low health-seeking among men emphasizes the necessity for co-creating an intervention that empowers them to self-manage their UI. We aim to co-create a self-management intervention with an older men and Health care provider (HCP) group and assess its usability and/or acceptability among older men with UI. The intervention mapping (IM) framework, a co-creation strategy, will be used to co-create a self-management tool, followed by usability and/or acceptability testing. The study will be guided by the first four IM steps: the logic model of the problem, the logic model of change, program/intervention design, and program/intervention production, followed by preliminary testing. A participatory group of older men with UI recruited from an existing group of patient partners, and continence care experts will be involved in all steps of the IM process. Usability and/or acceptability testing will be conducted on a sample of 20 users recruited through seniors' associations and retirement living facilities. After accessing the self-management tool for a week, participants will complete a product usability testing scale (aka System Usability Scale-SUS) and/or an acceptability test, depending on the preferred mode(s) of intervention delivery. Data will be analyzed using descriptive statistics. A benchmark overall mean usability score of 70 represents a good/usable product, based on the large database of SUS scores.

Association Between Preoperative Cannabis Use and Increased Rate of Revision Surgery Following Spinal Fusion: A Systematic Review and Meta-Analysis.

The use of cannabis as a method of chronic pain relief has skyrocketed since its legalization in states across the United States. Clinicians currently have a limited scope regarding the effectiveness of marijuana on surgical procedures. This systematic review aims to determine the effect of current cannabis use on the rate of failure of spinal fusions and overall surgical outcomes. A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. PubMed, Embase, and Scopus were searched, identifying studies assessing spinal fusion with reported preoperative cannabis use. Outcomes of interest included reoperation due to fusion failure or pseudoarthrosis with a follow-up time of at least six months. Subgroups of cervical fusions alone and lumbar fusions alone were also analyzed. Certainty in evidence and bias was assessed using the GRADE criteria and ROBINS-I tool (PROSPERO #CRD42023463548). Four studies met the inclusion criteria, with a total of 788 patients (188 in the cannabis user group and 600 in the non-user group). The rate of revision surgery among cannabis users was higher than that in non-users for all spinal fusions (RR: 3.58, 95% CI: 1.67 to 7.66, p = 0.001). For cervical fusions alone, there remained a higher rate of revision surgery for cannabis users compared to non-users (RR: 4.47, 95% CI: 1.93 to 10.36, p = 0.0005). For lumbar fusions alone, there was no difference in the rates of revision surgery between cannabis users and non-users (RR: 1.21, 95% CI: 0.28 to 7.73, p = 0.79). Cannabis use was shown to be associated with a higher rate of pseudoarthrosis revisions in spinal fusions on meta-analysis. On subgroup stratification by spine region, cannabis use remained associated with pseudoarthrosis revisions on cervical fusions alone but not lumbar fusions alone. Further research with larger, randomized studies is required to fully elucidate the relationship between cannabis use and fusion, both in general and by spinal region.

Defining and prioritizing modifiable risk factors towards the co-creation of a urinary incontinence self-management intervention for older men: A sequential multimethod study protocol.

Urinary incontinence (UI), characterized by involuntary urine leakage is a chronic, embarrassing and stigmatizing condition that is under-reported and under-treated). UI is under-prioritized and under-researched, particularly in older men (defined here as men 65+), and there have been calls for more targeted research focusing on this specific group. No existing self-management interventions focus on the needs of older men and none incorporate the perspectives of older men into their development. Furthermore, health inequalities and disparities in continence services for men, and a low level of health seeking behavior in men with UI make it crucial to incorporate their perspectives into intervention development to ensure optimal outcomes. The study will identify risk factors for UI that are potentially amenable to self-management in older men, assess their self-efficacy in managing UI, and determine what modifiable risk factors older men feel are pragmatic to include as part of a self-management program. We will conduct and report a sequential multi-method design consisting of a Delphi study among healthcare experts and a survey among older men with UI, according to the Guidance on Conducting and Reporting Delphi Studies (CREDES) Checklist and the Checklist for Reporting Of Survey Studies (CROSS). A geographically dispersed, multidisciplinary group of 30 health care professionals (urologists, geriatricians, family physicians, and nurses) involved in continence care and a representative sample of at least 128 ethnically diverse older men will participate in a Delphi survey and an older men's survey respectively. The healthcare experts will evaluate an evidence-synthesized list of UI risk factors to determine those potentially amenable to self-management. Delphi rounds will be repeated until consensus threshold of 75% is reached. Thereafter, older men recruited via stratified sampling of population subgroups will rate a list of expert-identified potentially modifiable risk factors to indicate which factors they deem practicable and can prioritize. Older men's survey questionnaires will capture information on patients' characteristics (socio-demographics and UI-related items). The Geriatric Self-Efficacy Index for UI (GSE-UI Index) as well as a Likert scale to assess perceived capability and willingness to modify the expert-identified UI modifiable risk factors will be included. Data will be analyzed quantitatively and qualitatively.

Deprescribing for older adults during acute care admission: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to understand the current body of knowledge regarding deprescribing in adults aged 60 and over in acute care settings, including the deprescribing activities that are being undertaken, and the feasibility, challenges, and outcomes of the practice. INTRODUCTION: Polypharmacy is prevalent amongst older adults, despite risks to patients. Much of the existing research on deprescribing has occurred in the outpatient context, with recent research emerging on the unique opportunity that acute care may provide. INCLUSION CRITERIA: This review will include deprescribing in adults aged 60 and older in acute care. It will consider deprescribing occurring during inpatient admission and at the time of discharge from hospital. METHODS: The JBI method for scoping reviews will guide this review. A search of MEDLINE (Ovid), Scopus, Web of Science, CINAHL (EBSCOhost), Embase (Ovid), and the Cochrane Database will be undertaken from inception to present with no language restrictions. Qualitative, quantitative, and mixed method studies, clinical practice guidelines, and opinion papers will be considered for inclusion. Systematic reviews and scoping reviews will be excluded. Google Scholar and a general Google search will be conducted for gray literature. Two reviewers will assess articles for inclusion and any disagreements will be discussed and resolved by discussion or a third reviewer, if required. Findings will be presented in the scoping review using a narrative approach with supporting quantitative data in a tabular format according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist (PRISMA-ScR). REVIEW REGISTRATION: Open Science Framework https://osf.io/pb7aw/.

Diagnosis of urinary tract infections in the hospitalized older adult population in Alberta.

BACKGROUND: Urinary tract infections (UTIs) are one of the most common infections reported in older adults, across all settings. Although a diagnosis of a UTI requires specific clinical and microbiological criteria, many older adults are diagnosed with a UTI without meeting the diagnostic criteria, resulting in unnecessary antibiotic treatment and their potential side effects, and a failure to find the true cause of their presentation to hospital. OBJECTIVE: The aim of this study was to evaluate the accuracy of UTI diagnoses amongst hospitalized older adults based on clinical and microbiological findings, and their corresponding antibiotic treatment (including complications), in addition to identifying possible factors associated with a confirmed UTI diagnosis. METHODS: A single-center retrospective cross-sectional study of older adult patients (n = 238) hospitalized at the University of Alberta Hospital with an admission diagnosis of UTI over a one-year period was performed. RESULTS: 44.6% (n = 106) of patients had a diagnosis of UTI which was supported by documents clinical and microbiological findings while 43.3% (n = 103) of patients had bacteriuria without documented symptoms. 54.2% (n = 129) of all patients were treated with antibiotics, despite not having evidence to support a diagnosis of a UTI, with 15.9% (n = 37) of those patients experiencing complications including diarrhea, Clostridioides difficile infection, and thrush. History of major neurocognitive disorder was significantly associated with diagnosis of UTI (p = 0.003). CONCLUSION: UTIs are commonly misdiagnosed in hospitalized older adults by healthcare providers, resulting in the majority of such patients receiving unnecessary antibiotics, increasing the risk of complications. These findings will allow for initiatives to educate clinicians on the importance of UTI diagnosis in an older adult population and appropriately prescribing antibiotics to prevent unwanted complications.

The characteristics of the implicit body model of the trunk.

Knowing where the body is in space requires reference to a stored model of the size and shape of body parts, termed the body model. This study sought to investigate the characteristics of the implicit body model of the trunk by assessing the position sense of midline and lateral body landmarks. Sixty-nine healthy participants localised midline and lateral body landmarks on their thorax, waist and hips, with perceived positions of these landmarks compared to actual positions. This study demonstrates evidence of a significant distortion of the implicit body model of the trunk, presenting as a squatter trunk, wider at the waist and hips. A significant difference was found between perceived and actual location in the horizontal (x) and vertical (y) directions for the majority of trunk landmarks. Evidence of a rightward bias was noted in the perception of six of the nine body landmarks in the horizontal (x) direction, including all midline levels. In the vertical (y) direction, a substantial inferior bias was evident at the thorax and waist. The implicit body model of the trunk is shown to be distorted, with the lumbar spine (waist-to-hip region) held to be shorter and wider than reality.

Safety, timing, and outcomes of early post-operative cardiac catheterisation following congenital heart surgery.

OBJECTIVE: The safety of early post-operative cardiac catheterisation has been described following congenital heart surgery. Optimal timing of early post-operative cardiac catheterisation remains uncertain. The aim of this study was to describe the safety of early post-operative cardiac catheterisation and its impact on cardiac ICU and hospital length of stay, duration of mechanical ventilation, and extracorporeal support. METHODS: This single-centre retrospective cohort study compared clinical and outcome variables between "early" early post-operative cardiac catheterisation (less than 72 hours after surgery) and "late" early post-operative cardiac catheterisation (greater than 72 hours after surgery) groups using Chi-squared, Student's t, and log-rank test (or appropriate nonparametric test). RESULTS: In total, 132 patients were included, 22 (16.7%) "early" early post-operative cardiac catheterisation, and 110 (83.3%) "late" early post-operative cardiac catheterisation. Interventions were performed in 63 patients (51.5%), 7 (11.1%) early and 56 (88.9%) late. Complications of catheterisation occurred in seven (5.3%) patients, two early and five late. There were no major complications. Patients in the late group trended towards a longer stay in the cardiac ICU (19 days [7, 62] versus 11.5 days [7.2, 31.5], p = 0.6) and in the hospital (26 days [9.2, 68] versus 19 days [13.2, 41.8], p = 0.8) compared to the earlier group. CONCLUSION: "Early" early post-operative cardiac catheterisation was associated with an overall low rate of complications. Earlier catheterisations trended towards shorter cardiac ICU and hospital length of stays. Earlier catheterisations may lead to earlier recovery for patients not following an expected post-operative course.

NITES, a nocturnal bladder score to aid diagnosis during the transition to older age care.

BACKGROUND: As adults transition to older age, bothersome nocturnal lower urinary tract symptoms (LUTS) become common. There is need for a reliable assessment metric to detect and measure specific symptoms. OBJECTIVE: To subject the nocturnal LUTS score for older individuals, Nocturia, Incontinence, Toileting and Enuresis Symptom Score (NITES), to psychometric analysis. MATERIAL AND METHODS: Factor analysis of the metric was conducted with completed questionnaires from 151 older individuals who were either admitted to a tertiary hospital or attending an outpatient continence clinic. Test re-test reliability involved 18 older community dwelling individuals attending a Geriatrician clinic completing the metric at two timepoints separated by at least 1 week. Intra-class correlation coefficients were determined for reliability of each factor and item. RESULTS: The NITES metric was completed by 98 hospitalized older individuals and 53 attending a continence clinic (mean age 83.2 years [SD 7.0]). Factor analysis demonstrated that one item had a floor effect and two items had poor endorsement. After test re-test reliability analysis, a further three items were removed: one due to poor correlation between timepoints and two demonstrating inadequate internal consistency. The final NITES metric is comprised of three factors: Sleep 4-items, Incontinence 4-items, and Personal Bother 2-items. A 4-item short form for symptom screening was extracted from the longer measure. CONCLUSION: The final NITES metric is a 10-item questionnaire with an embedded 4-item short symptom screen. It has utility utilized to detect nocturnal bladder symptoms in both community dwelling and hospitalized older adults.

Tactile localization accuracy at the low back.

Localizing tactile stimulation is an important capability for everyday function and may be impaired in people with persistent pain. This study sought to provide a detailed description of lumbar spine tactile localization accuracy in healthy individuals. Sixty-nine healthy participants estimated where they were touched at nine different points, labelled in a 3 × 3 grid over the lumbar spine. Mislocalization between the perceived and actual stimulus was calculated in horizontal (x) and vertical (y) directions, and a derived hypotenuse (c) mislocalization was calculated to represent the direct distance between perceived and actual points. In the horizontal direction, midline sites had the smallest mislocalization. Participants exhibited greater mislocalization for left- and right-sided sites, perceiving sites more laterally than they actually were. For all vertical values, stimulated sites were perceived lower than reality. A greater inaccuracy was observed in the vertical direction. This study measured tactile localization for the low back utilizing a novel testing method. The large inaccuracies point to a possible distortion in the underlying perceptual maps informing the superficial schema; however, further testing comparing this novel method with an established tactile localization task, such as the point-to-point method, is suggested to confirm these findings.

Should hormone replacement therapy (any route of administration) be considered in all postmenopausal women with lower urinary tract symptoms? Report from the ICI-RS 2023.

AIMS: This International Consultation on Incontinence-Research Society report aims to summarize the evidence and uncertainties regarding the use of hormone replacement therapy by any route in the management of lower urinary tract symptoms (LUTS) including recurrent urinary tract infections (rUTI), with a review of special considerations for the elderly. Research question proposals to further this field have been highlighted. METHODS: An overview of the existing evidence, guidelines, and consensus regarding the use of topical or systemic estrogens in the management of LUTS. RESULTS: There are currently evidence and recommendations to offer topical estrogens to postmenopausal women with overactive bladder symptoms as well as postmenopausal women with rUTIs. Systemic estrogens however have been shown in a meta-analysis to have a negative effect on LUTS and, therefore are not currently recommended. CONCLUSIONS: Although available evidence and recommendations exist for the use of topical estrogens, few women are commenced on these in primary care. There remain large gaps still within our knowledge of the use of estrogens within the management of LUTS, particularly on when it should be commenced, the length of time treatment should be continued for, and barriers to prescribing.

SETD1A variant-associated psychosis: A systematic review of the clinical literature and description of two new cases.

OBJECTIVE: SETD1A encodes a histone methyltransferase involved in various cell cycle regulatory processes. Loss-of-function SETD1A variants have been associated with numerous neurodevelopmental phenotypes, including intellectual disability and schizophrenia. While the association between rare coding variants in SETD1A and schizophrenia has achieved genome-wide significance by rare variant burden testing, only a few studies have described the psychiatric phenomenology of such individuals in detail. This systematic review and case report aims to characterize the neurodevelopmental and psychiatric phenotypes of SETD1A variant-associated schizophrenia. METHODS: A PubMed search was completed in July 2022 and updated in May 2023. Only studies that reported individuals with a SETD1A variant as well as a primary psychotic disorder were ultimately included. Additionally, another two previously unpublished cases of SETD1A variant-associated psychosis from our own sequencing cohort are described. RESULTS: The search yielded 32 articles. While 15 articles met inclusion criteria, only five provided case descriptions. In total, phenotypic information was available for 11 individuals, in addition to our own two unpublished cases. Our findings suggest that although individuals with SETD1A variant-associated schizophrenia may share a number of common features, phenotypic variability nonetheless exists. Moreover, although such individuals may exhibit numerous other neurodevelopmental features suggestive of the syndrome, their psychiatric presentations appear to be similar to those of general schizophrenia populations. CONCLUSIONS: Loss-of-function SETD1A variants may underlie the development of psychosis in a small percentage of individuals with schizophrenia. Identifying such individuals may become increasingly important, given the potential for advances in precision medicine treatment approaches.