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Setting: Despite Canada’s single-payer health system, marginalized populations often experience poor health outcomes and barriers to healthcare access. In response, mobile health clinics (MHCs) have been deployed in several cities across Canada. MHCs are well established in the United States; however, little is known about their role and impact in a country with universal healthcare. We describe the implementation of an urban MHC and early learnings from a mixed methods process and outcome-oriented evaluation. Intervention: In February 2021, Parkdale Queen West Community Health Centre, TELUS Health for Good, and University Health Network’s Gattuso Centre for Social Medicine partnered to launch a nurse practitioner‒led, community-based MHC in Toronto, Ontario. The MHC provides low-barrier primary healthcare, harm reduction, and mental health services at five convenient locations. Outcomes: Through an intercept survey (n= 49) and semi-structured interviews (n= 10), we sought to understand the sociodemographic characteristics of clients, their experiences at the MHC, and barriers and facilitators to the MHC in comparison to traditional healthcare settings. Most clients surveyed reported being homeless (61%). Without the MHC, 37% of clients would have accessed care at an emergency department and 18% would not have sought care. Thematic analysis revealed two structural and two relational factors that improved care experiences and care access. Implications: We demonstrate that in a single-payer health system, MHCs alleviate major barriers to care access for marginalized populations. Learnings provide context to the most salient factors influencing clients’ decisions to seek care at MHCs and can inform how these outreach models are designed.

Bleeding is common in patients with haematological malignancies undergoing intensive therapy. We aimed to assess the effect of tranexamic acid on preventing bleeding and the need for platelet transfusions.

Purpose: This study aims to understand global and segmental spinal ROM in surgical and nonsurgical AIS patients. Methods: This systematic review examined segmental vertebral ROM in AIS patients using PubMed, SPORTDiscus, MEDLINE, and Web of Science until October 8th, 2023. Inclusion criteria were articles on segmental motion in AIS patients, both operative and non-operative, under 18 years old. Results: Seventeen articles met eligibility criteria from 2511 initially retrieved. All patients (n= 996) had AIS (549 non-operative; 447 were operative), with a frequency-weighted mean age of 15.1 ± 1.6 years and a baseline Cobb angle of 51.4 ± 13.3 degrees. Studies showed heterogenous segmental flexibility in the unfused spine, with the apical curve and upper thoracic segments being more rigid and lower segments more flexible at -5 disk segments from the apex. Most studies showed a predictable loss of motion in fused spinal regions postoperatively and a variable loss of global motion depending on the LIV and number of fused segments. A 7° global loss of total trunk flexion per level was observed with increasingly caudal LIV, starting at L1. Anterior vertebral body tethering (AVBT) preserved motion post-surgery but reduced coronal plane motion. AVBT saw less motion loss compared to posterior spinal fusion (PSF) but had higher revision and complication rates. Conclusion: Preservation of spinal segments correlated with improved motion postoperatively. Increasing caudal LIV in PSF showed sagittal flexion loss. AVBT preserved more sagittal ROM than PSF but increased coronal motion loss, complications, and revision rates, with the largest benefit at LIV L4. Data on segmental motion are limited and further research on postoperative segmental ROM is required.

Reducing body weight to improve metabolic health and related comorbidities is a primary goal in treating obesity1,2. However, maintaining weight loss is a considerable challenge, especially as the body seems to retain an obesogenic memory that defends against body weight changes3,4. Overcoming this barrier for long-term treatment success is difficult because the molecular mechanisms underpinning this phenomenon remain largely unknown. Here, by using single-nucleus RNA sequencing, we show that both human and mouse adipose tissues retain cellular transcriptional changes after appreciable weight loss. Furthermore, we find persistent obesity-induced alterations in the epigenome of mouse adipocytes that negatively affect their function and response to metabolic stimuli. Mice carrying this obesogenic memory show accelerated rebound weight gain, and the epigenetic memory can explain future transcriptional deregulation in adipocytes in response to further high-fat diet feeding. In summary, our findings indicate the existence of an obesogenic memory, largely on the basis of stable epigenetic changes, in mouse adipocytes and probably other cell types. These changes seem to prime cells for pathological responses in an obesogenic environment, contributing to the problematic ‘yo-yo’ effect often seen with dieting. Targeting these changes in the future could improve long-term weight management and health outcomes.

ABSTRACT:Oral anticoagulation (OAC) prevents stroke in atrial fibrillation, yet a residual stroke risk remains. In this single-center retrospective analysis of acute ischemic stroke patients despite OAC, suboptimal OAC treatment is common (30%: inappropriate dosing (17%); patient non-adherence (13%)). Other causes of stroke included OAC interruption (14.5%), a competing stroke mechanism (11.0%), and undetermined breakthrough stroke in 44.5%. Overall, easily modifiable causes of ischemic stroke despite OAC are common. Accordingly, strategies to improve treatment compliance, including appropriate dosing along with guideline-based risk factor and periprocedural OAC management, should be emphasized to improve secondary stroke prevention in this patient population.

The use of intranasal (IN) analgesics and sedatives has been studied among pediatrics patients in the emergency department and outpatient settings. However, less is known about their usage in inpatient settings. This study aims to evaluate the indications and safety profile for IN fentanyl and midazolam usage in pediatric patients admitted to a large tertiary care children’s hospital.This study is a retrospective chart review of admitted patients receiving IN fentanyl and/or midazolam over a 6-year period. Indications for medication use, medication dosages, patient characteristics, and any serious adverse drug reactions were recorded. Reported serious adverse outcomes include use of reversal agents as well as any documented respiratory depression, hypotension, or need for escalation of care.Of 156 patients included, 119 (76%) received IN midazolam alone, 20 (13%) patients received IN fentanyl alone, and 17 (11%) patients received both medications. The most common applications for IN medication administration were nasogastric tube placements (n = 62), peripheral intravenous line insertions (n = 30), peripherally-inserted central catheter placements (n = 23), and lumbar punctures (n = 16). No serious adverse events were reported.This study suggests that IN fentanyl and midazolam were administered to pediatric inpatients undergoing routine procedures without serious adverse drug reactions being reported. Although these findings are encouraging, more prospective studies are needed before wider implementation of IN fentanyl and midazolam administration in pediatric inpatients.

Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory disease requiring long-term treatment. Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated tolerability and sustained clinical efficacy for up to 1 year for patients with PsA. Here, we report the longer-‍term safety and efficacy of bimekizumab up to 2 years. Methods: BE OPTIMAL (biologic disease-modifying antirheumatic drug [bDMARD]-naïve) and BE COMPLETE (prior inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi-IR]) assessed subcutaneous bimekizumab 160 mg every 4 weeks in patients with PsA. BE OPTIMAL included a reference arm (adalimumab 40 mg every 2 weeks); patients switched to bimekizumab at week 52 with no washout between treatments. BE OPTIMAL week 52 and BE COMPLETE week 16 completers were eligible for the BE VITAL open-label extension. Efficacy outcomes are reported to week 104/100 (BE OPTIMAL/BE COMPLETE). Results: A total of 710/852 (83.3%) bDMARD-naïve and 322/400 (80.5%) TNFi-IR patients completed week 104/100. Up to 104 weeks, patients treated with bimekizumab in BE OPTIMAL and BE COMPLETE had treatment-emergent adverse event incidence rates (exposure-adjusted incidence rate/100 patient-years) of 179.9 (95% CI 166.9, 193.7) and 100.3 (89.2, ‍112.4), respectively. The proportion of patients achieving efficacy outcomes (≥ 50% improvement from baseline in American College of Rheumatology [ACR] response criteria, 100% improvement from baseline in Psorisis Area and Severity Index [PASI], minimal disease activity [MDA]) was sustained in all patients from week 52 to week 104/100. Conclusions: Bimekizumab was well tolerated for up to 2 years of treatment and no new safety signals were observed. Sustained clinical efficacy was observed up to 2 years in bDMARD-naïve and TNFi-IR patients with active PsA. Patients switching from adalimumab to bimekizumab demonstrated further improvement in skin and nail symptoms, and sustained efficacy in joint symptoms. Trial Registration: BE OPTIMAL (NCT03895203), BE COMPLETE (NCT03896581), BE VITAL (NCT04009499).

Graphical abstract:

Corporate executive job demands may lead to poor sleep habits, increasing their risk for cardiometabolic disease. This study aimed to describe and explore associations between objectively measured habitual sleep characteristics and cardiometabolic disease risk of corporate executives, while accounting for occupational, psychological, and lifestyle factors.

Introduction: We evaluated the impact of gender on disease severity, health-related quality of life (HRQoL), treatment management, and patient–healthcare professional (HCP) interactions from the perspectives of patients with psoriatic arthritis (PsA). Methods: Data were collected from a global online patient survey conducted by The Harris Poll (November 2, 2017 to March 12, 2018). Eligible patients were aged ≥ 18 years, with a self-reported diagnosis of PsA for > 1 year, had visited a rheumatologist/dermatologist in the past 12 months, and had reported previously using ≥ 1 conventional synthetic or biologic disease-modifying antirheumatic drug. Data were stratified by gender and analyzed descriptively, inferentially by binomial (chi-square) tests, and by multivariate logistic regression models. Results: Data from 1286 patients who participated were included: 52% were female, 48% were male. Varying perceptions of disease severity between males and females were indicated by differences in symptoms leading to a diagnosis of PsA, and in symptoms reported despite treatment; more females than males reported joint tenderness, skin patches/plaques, and enthesitis. More females than males reported a major/moderate impact of PsA on their physical activity and emotional/mental well-being. Reasons for switching medication differed between genders, with more females switching because they perceived their medication to not be effective enough related to their joint symptoms. More females than males were very satisfied with their communication with their rheumatologist and were more likely to discuss the impact of PsA on their daily lives, their treatment satisfaction, and treatment goals with their rheumatologist. Conclusions: Patients’ perceptions of the impact of PsA on HRQoL, treatment management, and interactions with HCPs varied between males and females. More females than males reported major/moderate physical and emotional impacts of PsA. When treating patients, it is important for HCPs to consider the potential impact of gender on patients’ experience of PsA and its symptoms. Graphical Abstract:

Two heterometallic cyanometallate-driven Cu(II)/Co(III) coordination polymers, [{Cu2K(H2tipa)2(H2O)4}Co(CN)6]n·4nH2O (1) and [{Cu2(H2tea)2}3{Co(CN)6}2]n·10nH2O (2), were self-assembled from Cu(NO3)2, an aminoalcohol chelator (H3tipa, triisopropanolamine; or H3tea, triethanolamine), and K3[Co(CN)6]. The compounds were fully characterized by single-crystal and powder X-ray diffraction, FTIR spectroscopy, and thermogravimetric and elemental analyses, revealing 1D (1) and 2D (2) metal–organic architectures with 2C1 and hcbtopologies constructed from [Cu2K(H2tipa)2(H2O)2]3+or [Cu2(H2tea)2]2+blocks and [Co(CN)6]3–linkers. A detailed magnetic study of 1and 2was performed by variable-temperature magnetic susceptibility measurements and broken symmetry DFT calculations. These new compounds expand a family of heterometallic coordination polymers derived from hexacyanocobaltate(III) linkers, with compound 1also representing the first structurally characterized heterotrimetallic Cu/Co/K derivative.

Background: The incidence of oral cancer has exhibited a rise within the young population. Considering that oral potentially malignant disorders (OPMDs) can precede the development of oral cancer, it is imperative to conduct studies in this particular younger population. This study aimed to evaluate the frequency and conduct a comparative analysis of the clinical-demographic characteristics of OPMDs in two distinct age groups. Material and Methods: A retrospective analysis was conducted with patients diagnosed with leukoplakia, erythroplakia, and leukoerythroplakia between 1965 and 2020. The individuals were categorized into two groups: those aged up to 40 years (Group Younger) and those aged 41 years and above (Group Older). Results: A total of 640 lesions were subjected to analysis. Among these, patients aged up to 40 years constituted 10.63% of the sample, however, this proportion decreased significantly to 6.9% between 2010 and 2020. A predominant male representation was observed in both groups, with white lesions being the most common in both as well. However, the frequency of red or mixed lesions was significantly higher (p=0.034) in the older group, along with a higher prevalence of dysplastic lesions (26.9% versus 11.8%, p=0.01). Moreover, the older group exhibited a relatively higher percentage of smokers/ex-smokers (78.6%), compared to the younger group (61.5%, p=0.085) and alcohol consumers/ex-consumers (54.9% versus 22.7%, p=0.028). Elderly individuals exhibited an unfavorable progression (p=0.028). However, a logistic regression analysis identified as significant variables associated with malignant transformation, the presence of epithelial dysplasia, and red lesions diagnosed as erythroplakia. Conclusions: A declining frequency of OPMDs in young adults was observed over the years, whereas in older adults, these disorders exhibited an unfavorable progression. [ABSTRACT FROM AUTHOR]

AbstractScientific writing is a rewarding, challenging, and necessary part of research. Building skills in scientific writing is critical in graduate student training and provides the foundation for scientific communication at all professional levels. Despite the importance of writing in research, this skill remains a barrier to success for many students. We have developed a practical approach to minimize scientific writing barriers using student-driven, peer-exchange in combination with concrete project goals and dedicated writing group times for a graduate Scientific Writing course. Course topics were drawn from self-identified student challenge areas and presented using in-class activities and discussion. Students selected their semester-long project on which to work, including research proposals, thesis chapters, and manuscripts. Students exchanged two rounds of peer review that provided overview comments and detailed editorial feedback. At each stage of their project, students built on their previous work in response to peer and instructor feedback. All students made progress on their individual projects and the majority improved their skills in at least one challenge area. This student-directed approach to scientific writing offers an opportunity to empower students to improve their writing skills with an emphasis on establishing consistent writing habits that will benefit students throughout their professional careers.

Deucravacitinib, a tyrosine kinase 2 inhibitor, was assessed in a phase 2 trial in patients with active psoriatic arthritis (PsA). Here, we report effects of deucravacitinib from the patient perspective. This phase 2, double‐blind trial (NCT03881059) randomized patients with active PsA 1:1:1 to deucravacitinib 6 mg once daily (QD), 12 mg QD, or placebo, for 16 weeks. Key secondary end points were changes from baseline (CFBs) at week 16 in Health Assessment Questionnaire‐Disability Index (HAQ‐DI) and 36‐item Short‐Form Health Survey (SF‐36) physical component summary (PCS) scores. Additional patient‐reported outcomes (PROs) assessed disease impact, including fatigue, pain, and mental health. The mean CFBs in PROs and percentages of patients reporting improvements with minimum clinically important differences (MCIDs) or scores of greater than normal values were also assessed. This study comprised 203 patients (51.2% female; mean ± SD age, 49.8 ± 13.5 years). At week 16, the adjusted mean difference (95% confidence interval) versus placebo in HAQ‐DI and SF‐36 PCS CFB was significant for each deucravacitinib group (HAQ‐DI 6 mg, −0.26 [−0.42 to −0.10], P= 0.0020; HAQ‐DI 12 mg, −0.28 [−0.45 to −0.12], P= 0.0008; SF‐36 PCS 6 mg, 3.3 [0.9 to 5.7], P= 0.0062; SF‐36 PCS 12 mg, 3.5 [1.1 to 5.9], P= 0.0042). MCID at week 16 were reported for all PROs with either dose of deucravacitinib. Improvements of MCID or to normative values were reported by more patients receiving deucravacitinib than placebo. Deucravacitinib groups demonstrate significant and clinically meaningful improvements in PROs versus placebo in patients with active PsA, which warrants further study.

We sought to describe fluid cognition and its correlates among individuals with systemic lupus erythematosus (SLE). Participants (n = 199) were recruited from a population‐based cohort for a single study visit (October 2019 to May 2022). Fluid cognition was measured via the National Institutes of Health Toolbox Fluid Cognition Battery (including episodic memory, working memory, attention and inhibitory control, processing speed, and cognitive flexibility domains) and expressed as age‐corrected standard scores (mean 100, SD 15). Potential impairment was defined as a standard score >1.5 SD below the mean. Descriptive statistics were calculated and associations of various participant characteristics with the potential fluid cognition impairment were assessed with multivariable logistic regression. Participants’ mean age was 46.1 years; most were female (87.4%), Black (86.4%), and non‐Hispanic (95.0%). The mean overall fluid cognition score was 87.2; of the individual domains, the participants’ mean score was lowest on attention and inhibitory control (82.0). Working status (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.14–0.64) and higher self‐reported physical functioning (OR 0.46, 95% CI 0.28–0.75) and physical performance (OR 0.72, 95% CI 0.59–0.87) were associated with lower odds of fluid cognition impairment; lower educational attainment was associated with higher odds (OR 3.82, 95% CI 1.67–8.75). Self‐reported forgetfulness, neuropsychiatric damage, and depressive symptoms were not statistically significantly associated with potential impairment. Fluid cognition and, particularly, attention and inhibitory control were low in those with SLE relative to the general US population. Working status, higher physical functioning and performance, and higher educational attainment were associated with lower prevalence of potential impairment. Future work is needed to develop and implement interventions to help support cognition in individuals with SLE.

Some studies have shown that the incidence of type 2 diabetes increases after a diagnosis of COVID-19, although the evidence is not conclusive. However, the effects of the COVID-19 vaccine on this association, or the effect on other diabetes subtypes, are not clear. We aimed to investigate the association between COVID-19 and incidence of type 2, type 1, gestational and non-specific diabetes, and the effect of COVID- 19 vaccination, up to 52 weeks after diagnosis.

In this paper, we present an improved collision avoidance algorithm conceived to deal with zero-speed pedestrians in a crowd. A zero-speed pedestrian is a pedestrian who stops for a short, undefined period to rest, use a phone, or communicate with others, and then resumes walking later. Zero-speed pedestrians can be encountered in places such as shopping centers, sidewalks with retail stores, or public gatherings. When integrated into a crowd simulation, zero-speed pedestrians can cause blockages, particularly livelocks, as observed when using the Optimal Reciprocal Collision Avoidance (ORCA) algorithm. A livelock in a simulation is a situation where an agent is blocked but still has room to move. If the livelock is not handled properly, it will invalidate the simulation runs. We provide insight into the causes of livelocks and propose a modification of ORCA that successfully prevents livelocks from occurring in typical situations in which they can be observed using ORCA. Among other applications, this model can be used as a crowd management tool to evaluate the impact of zero-speed pedestrians on crowd flow.

The article examines the genesis of Prussian Conservatism in general and its models of representation rooting in a concept of ‘Protestant freedom’ in particular. By focusing on Conservatives’ adaption of concepts of party and freedom in the first half of the nineteenth century, the article shows that conservative adaption of contemporary political language and concepts was not a mere attempt of regaining dominance in public discourse but was rooted in specific concepts of Christian and Protestant thought. The article shows that conservative models of representation and participation are primarily not motivated by an opposition to liberal political thought but first of all the result of a politicisation of religious thought.

Because of their abundance and high emissions rates, small reservoirs (< 0.01 km2) can be important emitters of the greenhouse gases carbon dioxide and methane. However, emissions estimates from small reservoirs have lagged those of larger ones, and efforts to characterize small reservoir emissions have largely overlooked variations in emissions pathways, times, and locations. We intensively sampled four small reservoirs in Georgia, USA, during the summer to quantify the contribution and spatiotemporal variability of different emissions pathways (CO2and CH4diffusion, CH4ebullition). We used these data to evaluate the efficiency and accuracy of different sampling schemes. Every emissions pathway was dominant in one reservoir on one sampling day, and excluding ebullition caused misestimation between −89% and −15% of the total flux. Sampling only once daily caused misestimation between −78% and 45%, but sampling twice or just after dawn (07:00 h) reduced error. Sampling four or fewer locations caused misestimation between −85% and 366%, and our results indicated that 6–20 sampling locations may be needed for reasonable accuracy. The floating aquatic macrophyte Wolffiasp. (duckweed) appeared to exert control over emissions variability, and the consequences of not accounting for variability were greater in a duckweed‐covered reservoir. Our results indicate that sampling only at 10:00 h (modal sampling time of prior efforts) may lead to the erroneous conclusion that reservoirs with high photosynthetic biomass are CO2sinks rather than sources. Improving estimation accuracy by accounting for within‐reservoir variation in emissions will facilitate more strategic management of these abundant, anthropogenic ecosystems.

IMPORTANCE: Among women diagnosed with primary breast cancer (BC) at or younger than age 40 years, prior data suggest that their risk of a second primary BC (SPBC) is higher than that of women who are older when they develop a first primary BC. OBJECTIVE: To estimate cumulative incidence and characterize risk factors of SPBC among young patients with BC. DESIGN, SETTING, AND PARTICIPANTS: Participants were enrolled in the Young Women’s Breast Cancer Study, a prospective study of 1297 women aged 40 years or younger who were diagnosed with stage 0 to III BC from August 2006 to June 2015. Demographic, genetic testing, treatment, and outcome data were collected by patient surveys and medical record review. A time-to-event analysis was used to account for competing risks when determining cumulative incidence of SPBC, and Fine-Gray subdistribution hazard models were used to evaluate associations between clinical factors and SPBC risk. Data were analyzed from January to May 2023. MAIN OUTCOMES AND MEASURES: The 5- and 10- year cumulative incidence of SPBC. RESULTS: In all, 685 women with stage 0 to III BC (mean [SD] age at primary BC diagnosis, 36 [4] years) who underwent unilateral mastectomy or lumpectomy as the primary surgery for BC were included in the analysis. Over a median (IQR) follow-up of 10.0 (7.4-12.1) years, 17 patients (2.5%) developed an SPBC; 2 of these patients had cancer in the ipsilateral breast after lumpectomy. The median (IQR) time from primary BC diagnosis to SPBC was 4.2 (3.3-5.6) years. Among 577 women who underwent genetic testing, the 10-year risk of SPBC was 2.2% for women who did not carry a pathogenic variant (12 of 544) and 8.9% for carriers of a pathogenic variant (3 of 33). In multivariate analyses, the risk of SPBC was higher among PV carriers vs noncarriers (subdistribution hazard ratio [sHR], 5.27; 95% CI, 1.43-19.43) and women with primary in situ BC vs invasive BC (sHR, 5.61; 95% CI, 1.52-20.70). CONCLUSIONS: Findings of this cohort study suggest that young BC survivors without a germline pathogenic variant have a low risk of developing a SPBC in the first 10 years after diagnosis. Findings from germline genetic testing may inform treatment decision-making and follow-up care considerations in this population.