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A randomized controlled trial established initial efficacy of a novel parent training (PT) intervention for improving oral hygiene and oral health in underserved children with ASD (Fenning et al., 2022), a population at risk for unmet dental needs. The present study describes our emic approach to PT development alongside treatment outcome data examining feasibility, acceptability, and engagement. Families with Medicaid-eligible children with ASD ages 3 to 13 years (85% male, 62% with intellectual disability) were assigned to receive PT (n = 60) or a psychoeducational toolkit (n = 59). Results indicate strong retention, fidelity, and adherence, with quantitative and qualitative metrics revealing high treatment satisfaction and utilization. Discussion focuses on implications for individualizing treatment to optimize engagement of underrepresented families.

Abstract Background Epigenetic scores (EpiScores), reflecting DNA methylation (DNAm)-based surrogates for complex traits, have been developed for multiple circulating proteins. EpiScores for pro-inflammatory proteins, such as C-reactive protein (DNAm CRP), are associated with brain health and cognition in adults and with inflammatory comorbidities of preterm birth in neonates. Social disadvantage can become embedded in child development through inflammation, and deprivation is overrepresented in preterm infants. We tested the hypotheses that preterm birth and socioeconomic status (SES) are associated with alterations in a set of EpiScores enriched for inflammation-associated proteins. Results In total, 104 protein EpiScores were derived from saliva samples of 332 neonates born at gestational age (GA) 22.14 to 42.14 weeks. Saliva sampling was between 36.57 and 47.14 weeks. Forty-three (41%) EpiScores were associated with low GA at birth (standardised estimates |0.14 to 0.88|, Bonferroni-adjusted p-value

Abstract Background Pediatric-type diffuse high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (IHG) but also in other pHGG and are associated with devastating morbidity and mortality. Methods To identify new treatment options, we established and characterized two novel orthotopic mouse models harboring distinct MET fusions. These included an immunocompetent, murine allograft model and patient-derived orthotopic xenografts (PDOX) from a MET-fusion IHG patient who failed conventional therapy and targeted therapy with cabozantinib. With these models, we analyzed the efficacy and pharmacokinetic properties of three MET inhibitors, capmatinib, crizotinib and cabozantinib, alone or combined with radiotherapy. Results Capmatinib showed superior brain pharmacokinetic properties and greater in vitro and in vivo efficacy than cabozantinib or crizotinib in both models. The PDOX models recapitulated the poor efficacy of cabozantinib experienced by the patient. In contrast, capmatinib extended survival and induced long-term progression-free survival when combined with radiotherapy in two complementary mouse models. Capmatinib treatment increased radiation-induced DNA double-strand breaks and delayed their repair. Conclusions We comprehensively investigated the combination of MET inhibition and radiotherapy as a novel treatment option for MET-driven pHGG. Our seminal preclinical data package includes pharmacokinetic characterization, recapitulation of clinical outcomes, coinciding results from multiple complementing in vivo studies, and insights into molecular mechanism underlying increased efficacy. Taken together, we demonstrate the groundbreaking efficacy of capmatinib and radiation as a highly promising concept for future clinical trials.

Abstract Background Hepatitis B is endemic amongst the Australian Aboriginal population in the Northern Territory. A participatory action research project identified the lack of culturally appropriate education tools and led to the development of the “Hep B Story” app in the Aboriginal language Yolŋu Matha. This paper describes a formal evaluation of the app’s first version, which informed improvements and translation into a further ten Aboriginal languages. Methods The evaluation employed Participatory Action Research (PAR) principles to work within Indigenous research methodologies and prioritise Indigenous knowledge to improve the app iteratively. Semi-structured interviews and focus groups were conducted across the Northern Territory with 11 different language groups. Local Community Based Researchers and Aboriginal Research team members coordinated sessions. The recorded, translated conversations were transcribed verbatim and thematically analysed using an inductive and deductive approach. Results Between November 2018 and September 2020, 94 individuals from 11 language groups participated in 25 semi-structured interviews and 10 focus groups. All participants identified as Aboriginal. Most participants felt the app would be culturally appropriate for Aboriginal communities in the Northern Territory and improve knowledge surrounding hepatitis B. The information gathered from these interviews allowed for identifying five main themes: support for app, relationships, concept versus language, shame, and perceptions of images, along with errors that required modification. Conclusions A “real-life” evaluation of the app was comprehensively completed using a PAR approach blended with Indigenous research methods. This evaluation allowed us to develop an updated and enhanced version of the app before creating the additional ten language versions. An iterative approach alongside strong community engagement was pivotal in ensuring the app’s cultural safety and appropriateness. We recommend avoiding the use of knowledge-based evaluations in an Aboriginal setting to ensure relevant and culturally appropriate feedback is obtained.

Abstract Neoadjuvant cisplatin-based chemotherapy is standard of care for muscle-invasive bladder cancer (MIBC). Immune checkpoint inhibition (ICI) alone, and ICI in combination with chemotherapy, have demonstrated promising pathologic response (

Abstract Despite a wealth of studies documenting prey responses to perceived predation risk, researchers have only recently begun to consider how prey integrate information from multiple cues in their assessment of risk. We conduct a systematic review and meta-analysis of studies that experimentally manipulated perceived predation risk in birds and evaluate support for three alternative models of cue integration: redundancy/equivalence, enhancement, and antagonism. One key insight from our analysis is that the current theory, generally applied to study cue integration in animals, is incomplete. These theories specify the effects of increasing information level on mean, but not variance, in responses. In contrast, we show that providing multiple complementary cues of predation risk simultaneously does not affect mean response. Instead, as information richness increases, populations appear to assess risk more accurately, resulting in lower among-population variance in response to manipulations of perceived predation risk. We show that this may arise via a statistical process called maximum-likelihood estimation (MLE) integration. Our meta-analysis illustrates how explicit consideration of variance in responses can yield important biological insights.

AbstractUnderstanding the roles of land surface conditions and atmospheric circulation on continental daily temperature variance is key to improving predictions of temperature extremes. Evaporative resistance (rs, hereafter), a function of the land cover type, reflects the ease with which water can be evaporated or transpired and is a strong control on land–atmosphere interactions. This study explores the effects of rs perturbations on summer daily temperature variance using the Simple Land Interface Model (SLIM) by mimicking, for rs only, a global land cover conversion from forest to crop/grassland. Decreasing rs causes a global cooling. The cooling is larger in wetter areas and weaker in drier areas, and primarily results from perturbations in shortwave radiation (SW) and latent heat flux (LH). Decreasing rs enhances cloud cover due to greater land surface evaporation and thus reduces incoming SW over most land areas. When rs decreases, wetter areas experience strong evaporative cooling, while drier areas become more moisture-limited and thus experience less cooling. Thermal advection further shapes the temperature response by damping the combined impacts of SW and LH. Temperature variance increases in drier areas and decreases in wetter areas as rs decreases. The temperature variance changes can be largely explained from changes in the combined variance of SW and LH, including an important contribution of changes in the covariance of SW and LH. In contrast, the effects of changes in thermal advection variance mainly affect the Northern Hemisphere midlatitudes.Significance StatementThis study aims to better understand processes governing daily near-surface air temperature variance over land. We use an idealized modeling framework to explore the effects of land surface evaporative resistance (a parameter that controls how hard it is to evaporate water from the surface) on summer daily temperature variance. We find that a uniform decrease of evaporative resistance across the global land surface causes changes in the temperature variance that can be predicted from changes in the combined variance of shortwave radiation and latent heat flux. The variance of horizontal advection is important in altering the temperature variance in the Northern Hemisphere midlatitudes. Our findings shed light on predicting the characteristics of temperature variability as a function of surface conditions.

BACKGROUND: Given the highly stressful environment surrounding the SARS-CoV-2 pandemic, healthcare workers (HCW) and public safety personnel (PSP) are at an elevated risk for adverse psychological outcomes, including posttraumatic stress disorder (PTSD) and alcohol/substance use problems. As such, the study aimed to identify associations between PTSD severity, related dissociation and emotion dysregulation symptoms, and alcohol/substance use problems among HCWs and PSP. METHODS: A subset of data (N = 498; HCWs = 299; PSP = 199) was extracted from a larger study examining psychological variables among Canadian HCWs and PSP during the pandemic. Structural equation modelling assessed associations between PTSD symptoms and alcohol/substance use-related problems with dissociation and emotion dysregulation as mediators. RESULTS: Among HCWs, dissociation fully mediated the relation between PTSD and alcohol-related problems (indirect effect β = .133, p = .03) and emotion dysregulation partially mediated the relation between PTSD and substance-related problems (indirect effect β = .151, p = .046). In PSP, emotion dysregulation fully mediated the relation between PTSD and alcohol-related problems (indirect effects β = .184, p = .005). For substance-related problems among PSP, neither emotion dysregulation nor dissociation (ps >.05) had any effects. CONCLUSION: To our knowledge, this is the first study examining associations between PTSD severity and alcohol/substance use-related problems via mediating impacts of emotion dysregulation and dissociation among HCWs and PSP during the SARS-CoV-2 pandemic. These findings highlight dissociation and emotion dysregulation as important therapeutic targets for structured interventions aimed at reducing the burden of PTSD and/or SUD among Canadian HCWs or PSP suffering from the adverse mental health impacts of the SARS-CoV-2 pandemic.

BackgroundVeterans with post-traumatic stress disorder (PTSD) are more likely to report chronic pain than veterans without PTSD. Yoga has been shown to reduce both chronic pain and PTSD symptoms in clinical trials. The goal of our study was to assess the feasibility and acceptability of conducting a randomized controlled trial (RCT) that combined yoga and mantram repetition (Yoga + MR) into one program for military veterans with both chronic pain and PTSD.MethodsIn this feasibility RCT, 27 veterans were randomized to either Yoga + MR or a relaxation intervention. Due to the COVID-19 pandemic, in-person recruitment, assessments, and intervention attendance were re-evaluated. Although remote delivery of aspects of the study were utilized, interventions were delivered in-person. Feasibility benchmarks met included full recruitment in 12 months or less, 75%+ retention at initial follow-up assessment, 50%+ attendance rate, and 75%+ of participants satisfied with the interventions.ResultsThe sample was racially and ethnically diverse, and 15% of participants were women. Participant recruitment lasted approximately 11 months. Out of 32 participants initially randomized, two participants asked to be dropped from the study and three did not meet PTSD symptom criteria. For the remaining 27 participants, retention rates were 85% at 12 weeks and 81% at 18 weeks. Participants attended 66% of in-person yoga and 55% of in-person relaxation sessions. Satisfaction was high, with 100% of yoga participants and 75%/88% of relaxation participants agreeing or strongly agreeing they were satisfied with the intervention/instructors. After 12 weeks (end of intervention), Yoga + MR participants reported reduced back-pain related disability (primary outcome), reduced alcohol use, reduced fatigue, and increased quality of life, while relaxation group participants reported reductions in pain severity, PTSD symptoms, and fatigue.ConclusionsAmidst many research challenges during the pandemic, recruitment, retention, and efficacy results from this feasibility trial support advancement to a larger RCT to study Yoga + MR for chronic pain and PTSD.

ObjectiveThe presence of macroscopic residual disease after primary cytoreductive surgery (PCS) is an important factor influencing survival for patients with high-grade serous ovarian cancer (HGSC). More research is needed to identify factors associated with having macroscopic residual disease. We analyzed 12 lifestyle and personal exposures known to be related to ovarian cancer risk or inflammation to identify those associated with having residual disease after surgery.MethodsThis analysis used data on 2054 patients with advanced stage HGSC from the Ovarian Cancer Association Consortium. The exposures were body mass index, breastfeeding, oral contraceptive use, depot-medroxyprogesterone acetate use, endometriosis, first-degree family history of ovarian cancer, incomplete pregnancy, menopausal hormone therapy use, menopausal status, parity, smoking, and tubal ligation. Logistic regression models were fit to assess the association between these exposures and having residual disease following PCS.ResultsMenopausal estrogen-only therapy (ET) use was associated with 33% lower odds of having macroscopic residual disease compared to never use (OR = 0.67, 95%CI 0.46-0.97, p = 0.033). Compared to nulliparous women, parous women who did not breastfeed had 36% lower odds of having residual disease (OR = 0.64, 95%CI 0.43-0.94, p = 0.022), while there was no association among parous women who breastfed (OR = 0.90, 95%CI 0.65-1.25, p = 0.53).ConclusionsThe association between ET and having no macroscopic residual disease is plausible given a strong underlying biologic hypothesis between this exposure and diagnosis with HGSC. If this or the parity finding is replicated, these factors could be included in risk stratification models to determine whether HGSC patients should receive PCS or neoadjuvant chemotherapy.

Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8+ and CD4+ T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.

In this systematic evaluation of intervention research for transition-age autistic youth, we examined quality indicators in 193 group and single-case design intervention studies, which tested effects on 1258 outcomes. Behaviorally based interventions were the most common intervention type. We found significant threats to internal validity for the majority of studies, including inadequate randomization, unmasked assessors, and too few data points to infer functional relations. The majority of outcomes were measured in contexts similar to the intervention and were conceptualized as behaviors directly addressed by intervention procedures. As such, they are of unclear long-term utility for autistic people entering adulthood. Adverse events were rarely reported. We suggest several avenues for improving intervention research for this age group.

Parents are expected to exhibit intermediate levels of investment in parental care that reflect the trade-off between current versus future reproduction. Providing parents with supplemental food may allow for increased care to the current brood (additive model), re-allocation of parental effort to other behaviours such as self-maintenance (substitution model), or may provide parents with a buffer against provisioning shortfalls (insurance model). We investigated the impact of parental food supplementation on provisioning behaviour and breeding success in Arctic-breeding peregrine falcons (Falco peregrinus tundrius) over five successive breeding seasons (2013−2017). We found that supplemental feeding had no impact on mean provisioning rates, yet resulted in increased nestling survival probability, increased nestling body mass and decreased variance in nestling body mass and provisioning rates. These results are consistent with parents adopting a hybrid of the additive and substitution models. We suggest that food supplementation enables increased investment in other forms of parental care (e.g. nest defence, brooding) without altering mean provisioning rates. The lack of observed effects on mean provisioning rates, coupled with increased survival and body mass of offspring, suggests a potential reallocation of parental effort. The findings contribute to understanding the responses of peregrine falcons to food supplementation, highlighting the need for future studies to explore broader environmental contexts and potential long-term effects on parental survival and future reproduction.

Background Specialist forensic community teams for people with intellectual disability and/or autism have been developed, but little is known about their extent and delivery. Aims To describe specialist forensic community teams for people with intellectual disability and/or autism across the UK. Method An online survey was sent to representatives of each UK Trust/Health Board providing adult mental health and/or intellectual disability services. Questions covered the availability, structure and activities of specialist community forensic services. Quantitative data were summarised and associations between access to specialist forensic teams and care were tested with Chi-squared tests. Thematic analysis of free-text survey responses was used to understand the challenges of providing community forensic mental health services for this group. Results A total of 49 out of 78 (63%) eligible Trusts/Health Boards responded, of which 25 (51%) had access to a specialist forensic community team. Teams operated either as part of a single Trust/Board (n = 13) or over a larger regional footprint (n = 12). The availability of specialist forensic community teams was associated with better access to offence-related interventions (χ2 = 15.1002, P < 0.005) and co-production of patient care plans (χ2 = 7.8726, P = 0.005). Respondents reported a wide variation in availability, expertise and perceived quality of community services. The availability of secure and generic in-patient beds, commissioning and legal barriers were also significant challenges in providing appropriate care. Conclusions Coverage of specialist community forensic teams is not universal. There are indications that such teams are associated with improved care processes, but further work is needed to establish longer-term outcomes and the optimal model of care.

Background: Patients with multiple myeloma (MM) are at risk of venous thromboembolism (VTE), worsened by immunomodulatory drugs. Although antithrombotics are recommended for prophylaxis, existing guidelines are suboptimal and treatment outcomes remain unclear. Objectives: This study aimed to investigate adverse events, antithrombotic utilization, and their associations with survival outcomes in patients with MM initiating multi-drug immunomodulatory combinations. Design: A posthoc analysis of individual-participant level data (IPD). Methods: IPD from three daratumumab clinical trials (MAIA, POLLUX, and CASTOR) were pooled. Adverse events incidence and antithrombotic utilization were assessed. Logistic and Cox regression were utilized to examine associations between antithrombotics use with adverse events and survival outcomes at the baseline and 6-month landmark. Results: Among 1804 patients, VTE occurred in 10%, bleeding in 14%, ischemic heart disease in 4%, and stroke in 2%. Patients with these adverse events demonstrated elevated rates of any grade ⩾3 events. Antiplatelet (primarily aspirin) and anticoagulant (primarily LMWH and direct oral anticoagulants) prescriptions have seen an increase from baseline (25% and 14%, respectively) to 6 months (35% and 31%). The primary indication for their use was prophylaxis. Anticoagulant use within 6 months was associated with reduced VTE (OR (95% CI) = 0.45 (0.26–0.77), p = 0.004), while antiplatelet use showed no associations with any evaluated adverse events. Antithrombotics and survival outcomes had no significant associations. Conclusion: This study underscores the complexities of antithrombotic therapy and adverse events in MM and highlights the need for vigilant and proactive management due to increased grade ⩾3 adverse events. While anticoagulant use was associated with reduced VTE risk, further research is needed to optimize thromboprophylaxis guidelines and explore antithrombotic efficacy and safety in patients with MM. Trial registration: MAIA (NCT02252172), POLLUX (NCT02076009), CASTOR (NCT02136134).

Translocation of captive-bred animals is a widely used conservation strategy to support the recovery of imperiled wild populations. Identifying which factors enhance or limit survival after release can be important in adapting translocation strategies, particularly for species with low survival rates after release from captivity. Many translocation programs track post-translocation survival, but few complete spatial-statistical assessments of mortality risk associated with release environments. Typically, few animals are released from captive breeding programs, limiting the sample size available for analyses. We aimed to create a workflow that used limited datasets to evaluate the influence of spatial conditions and other factors on mortality risk. Greater sage-grouse (Centrocercus urophasianus) are endangered in Canada and of conservation concern throughout their range in the United States. After the species declined precipitously in Canada, a captive breeding program was initiated with subsequent releases in Alberta and Saskatchewan. Despite success in captive breeding, mortality rates of released sage-grouse were high. We used GPS- and VHF-based locations of released sage-grouse to determine how spatial features influence mortality risk of sage-grouse after release from captivity. We implemented a multistep approach to quantify and map risk relative to the environmental features associated with mortality. We also assessed whether the movement behaviors of sage-grouse correspond with environmental risk factors by using a combination of survival models and integrated step-selection functions. Mortality of sage-grouse in Alberta was hastened in areas close to anthropogenic disturbance. Although birds in Alberta avoided areas of higher mortality risk, those in Saskatchewan did not, perhaps due to environmental and selection constraints. This multistep approach allowed us to utilize small sample sizes to assess key risk factors in the landscape. This process supports the adaptive modification of translocation plans and can similarly support other data-limited scientists and managers in assessing environmental mortality risk and defining conservation actions for endangered species.

Background There is limited evidence regarding the optimal time to commence parenteral nutrition (PN) in term and late preterm infants.Design Single-centre, non-blinded, exploratory randomised controlled trial.Setting A level-3 neonatal unit in a stand-alone paediatric hospital.Patients Infants born ≥34 weeks of gestation and ≤28 days, who needed PN. Eligible infants were randomised on day 1 or day 2 of admission.Interventions Early (day 1 or day 2 of admission, N=30) or late (day 6 of admission, N=30) PN.Main outcome measures Plasma phenylalanine and F2-isoprostane levels on day 4 and day 8 of admission. Secondary outcomes were amino-acid and fatty-acid profiles on day 4 and day 8, and clinical outcomes.Results The postnatal age at randomisation was similar between the groups (2.3 (SD 0.8) vs 2.3 (0.7) days, p=0.90). On day 4, phenylalanine levels in early-PN infants were higher than in late-PN (mean (SD) 62.9 (26.7) vs 45.5 (15.3) µmol/L; baseline-adjusted percentage difference 25.8% (95% CI 11.6% to 39.9%), p

Abstract Objective To evaluate the cost‐effectiveness of various topical prophylaxis strategies against posttympanostomy otorrhea using a break‐even analysis. Study Design An economic decision analysis of data collected from purchasing records and the literature. Setting An academic center. Methods Costs of various strategies were calculated by querying our institution's pharmacy as well as GoodRX.com drug prices. Posttympanostomy otorrhea rates were acquired from a review of the literature. Costs for treatment of otorrhea were based upon our institution's self‐pay patient charges. A break‐even analysis was performed to determine the required absolute risk reduction (ARR) in otorrhea rate to make prophylactic treatment cost‐effective. Results The most expensive strategy ciprofloxacin/hydrocortisone otic ($626.83) was not cost‐effective unless the rate of postoperative otorrhea was greater than 92% or if the cost of otorrhea treatment exceeded $4477.36. The cheapest antibiotic/steroid combination, ciprofloxacin/dexamethasone otic ($72.25) was cost‐effective (ARR 10%). Using a conservative initial otorrhea rate (14%) and weighted cost of treatment ($683.39), the most expensive cost‐effective prophylactic intervention possible was $95.67. Conclusion Prophylaxis against posttympanostomy otorrhea can be cost‐effective. Physicians should consider the cost of prophylaxis at their institution as well as the patient's postoperative risk of otorrhea when making treatment decisions.

Editorial introducing a new special issue in the journal.

Background Ivacaftor approval was extended to people with cystic fibrosis (CF) with ≥1 of 28 additional ivacaftor-responsive mutations in the USA in 2017 based on preclinical in vitro data. This retrospective, observational study assessed real-world clinical response to ivacaftor in people with CF with ≥1 of these mutations, using data from the US Cystic Fibrosis Foundation Patient Registry.Methods Participants aged ≥2 years with ≥1 of 28 eligible mutations initiating ivacaftor between May 2017 and December 2018 were included. Clinical outcomes data were evaluated for ≤1 year before and ≤2 years after ivacaftor initiation. Participants initiating ivacaftor between May and December 2017 (2017 cohort) were used for the primary analysis because up to 2 years of post-ivacaftor-initiation data were available. Analyses were descriptive; key outcomes included percent predicted forced expiratory volume in 1 s (ppFEV1), body mass index (BMI) and BMI z-score, pulmonary exacerbations (PEx) and hospitalisations.Results The study included 1004 eligible participants. In the 2017 cohort (n=613), mean absolute change in ppFEV1 from pre-ivacaftor initiation was 1.9 (95% CI 1.4, 2.4) and 1.8 (95% CI 1.0, 2.7) percentage points in years 1 and 2 post-ivacaftor initiation, respectively; mean absolute change in BMI was 0.6 (95% CI 0.5, 0.7) and 1.0 (95% CI 0.8, 1.2) kg/m2 in years 1 and 2, respectively; BMI z-score was unchanged. Annualised event rates of PEx and hospitalisations per patient-year were lower with ivacaftor (0.24 (95% CI 0.21, 0.26) and 0.28 (95% CI 0.25, 0.31), respectively) compared with pre-ivacaftor initiation (0.41 (95% CI 0.37, 0.46) and 0.45 (95% CI 0.41, 0.49), respectively).Conclusions These real-world observational study findings support the effectiveness of ivacaftor in people with CF aged ≥2 years with selected CFTR mutations.

Summary: Background: The Northern Territory (NT) has the highest prevalence of chronic hepatitis B (CHB) in Australia. The Hep B PAST program aims to improve health outcomes for people living with CHB. Methods: This mixed methods study involves First Nations peoples living in the NT. We used participatory action research principles across three steps: 1. Foundation step: establishing hepatitis B virus (HBV) status and linkage to care; 2. Capacity building: training the health workforce; 3. Supported transition to primary healthcare: implementation of the “Hub and Spoke” model and in-language resources. Analysis occurred at three time points: 1. Pre-Hep B PAST (2018); 2. Foundation step (2020); and 3. Completion of Hep B PAST (2023). Evaluation focuses on four key indicators, the number of people: 1) with documented HBV status; 2) diagnosed with CHB; 3) receiving care; and 4) receiving treatment. Findings: Hep B PAST (2018–23) reached 40,555 people. HBV status was documented in 11% (1192/10,853), 79.2% (26,075/32,915) and 90.8% (28,675/31,588) of people at pre-Hep B PAST, foundation step, and completion respectively. An estimated 99.9% (821/822) of people were diagnosed, 86.3% (709/822) engaged in care, and 24.1% (198/822) on antiviral treatment at completion. CHB prevalence in the study population is 2.6%, decreasing from 6.1% to 0.4% in the pre- and post-vaccination cohorts. Interpretation: Hep B PAST is an effective model of care. Partner health services are exceeding elimination targets. This model could enable other countries to enhance the cascade of care and work towards eliminating HBV. Funding: National Health and Medical Research Council.

BackgroundChronic low back pain (cLBP) and chronic neck pain (cNP) are highly prevalent conditions and common reasons for disability among military personnel. Yoga and other mind-body interventions have been shown to safely decrease pain and disability in persons with cLBP and/or cNP but have not been adequately studied in active duty military personnel. The objective of this study was to examine the feasibility and acceptability of delivering 2 types of yoga (hatha and restorative) to a sample of active-duty military personnel with cLBP/cNP.MethodsMilitary personnel with cLBP and/or cNP (n = 49; 59% men) were randomized to either hatha or restorative yoga interventions. Interventions consisted of in-person yoga 1-2x weekly for 12 weeks. Feasibility and acceptability were measured by rates of recruitment, intervention attendance, attrition, adverse events, and satisfaction ratings. Health outcomes including pain and disability were measured at baseline, 12 weeks, and 6 months. Means and effect sizes are presented.ResultsRecruitment was completed ahead of projections. Over 90% of participants agreed or strongly agreed that they enjoyed participation, liked the instructor, and would like to continue yoga. Retention rates were 86% and 80% at 12 week and 6 month assessments, respectively. Intervention attendance was adequate but lower than expected. There were small to moderate reductions in back-pain related disability, pain severity and pain interference, and improvements in quality of life, grip strength, and balance. In general, effects were larger for those who attended at least 50% of intervention classes. Participants with cNP tended to have smaller outcome improvements, but conclusions remain tentative given small sample sizes.ConclusionsResults demonstrate feasibility for conducting a randomized controlled comparative effectiveness trial of yoga for cLBP and cNP among active duty military personnel. Acceptability was also established. Ongoing work will enhance the intervention for cNP and establish feasibility at another military facility in preparation for a fully-powered comparative effectiveness trial.ClinicalTrials #NCT03504085; registered April 20, 2018.

BACKGROUND: Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence. METHODS: We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples. RESULTS: We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1β, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here. CONCLUSIONS: Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.

Abstract Background Multiple studies have indicated that patients with high body mass index (BMI) may have favourable survival outcomes following treatment with an immune checkpoint inhibitor (ICI). However, this evidence is limited by several factors, notably the minimal evidence from randomised controlled trials (RCTs), the use of categorised BMI with inconsistent cut point definitions, and minimal investigation of contemporary combination ICI therapy. Moreover, whether overweight and obese patients gain a larger benefit from contemporary frontline chemoimmunotherapy in non-small cell lung cancer (NSCLC) is unclear. Methods This secondary analysis pooled individual patient data from the intention-to-treat population of the IMpower130 and IMpower150 RCTs comparing chemoimmunotherapy versus chemotherapy. Co-primary outcomes were overall survival (OS) and progression-free survival (PFS). The potentially non-linear relationship between BMI and chemoimmunotherapy treatment effect was evaluated using Multivariable Fractional Polynomial Interaction (MFPI). As a sensitivity analysis, chemoimmunotherapy treatment effect (chemoimmunotherapy versus chemotherapy) on survival was also estimated for each BMI subgroup defined by World Health Organisation classification. Exploratory analyses in the respective chemoimmunotherapy and chemotherapy cohort were undertaken to examine the survival outcomes among BMI subgroups. Results A total of 1282 patients were included. From the MFPI analysis, BMI was not significantly associated with chemoimmunotherapy treatment effect with respect to either OS (p = 0.71) or PFS (p = 0.35). This was supported by the sensitivity analyses that demonstrated no significant treatment effect improvement in OS/PFS among overweight or obese patients compared to normal weight patients (OS: normal BMI HR = 0.74 95% CI 0.59–0.93, overweight HR = 0.78 95% CI 0.61–1.01, obese HR = 0.84 95% CI 0.59–1.20). Exploratory analyses further highlighted that survival outcomes were not significantly different across BMI subgroups in either the chemoimmunotherapy therapy cohort (Median OS: normal BMI 19.9 months, overweight 17.9 months, and obese 19.5 months, p = 0.7) or the chemotherapy cohort (Median OS: normal 14.1 months, overweight 15.9 months, and obese 16.7 months, p = 0.7). Conclusion There was no association between high BMI (overweight or obese individuals) and enhanced chemoimmunotherapy treatment benefit in front-line treatment of advanced non-squamous NSCLC. This contrasts with previous publications that showed a superior treatment benefit in overweight and obese patients treated with immunotherapy given without chemotherapy.

Abstract Background Medication management capacity is a crucial component of medication adherence, particularly among older adults. Various factors, including physical abilities, cognitive functions, sensory capabilities, motivational, and environmental factors, influence older adults' ability to manage medications. It is, therefore, crucial to identify appropriate tools that allow clinicians to determine which factors may impact medication management capacity and, consequently, nonadherence to medications. Purpose 1)To identify tools that measure physical, cognitive, sensory (vision, hearing, touch), motivational, and environmental barriers to medication self-management in older adults, and 2) to understand the extent to which these tools assess various barriers. Methods The scoping review was conducted using Arksey and O'Malley's scoping review framework and the PRISMA Extension for Scoping Reviews checklist. In June 2022, the relevant literature was identified by searching PubMed (MEDLINE), Ovid Embase, Ovid IPA, EBSCOhost CINAHL, APA PsycINFO, and Scopus. Results and discussion In total, 7235 studies were identified. Following the removal of duplicates, 4607 articles were screened by title and abstract, of which 4253 did not meet the inclusion criteria. Three reviewers reviewed the full texts of the remaining 354 articles; among them, 41 articles, 4 theses and 1 conference abstract met the inclusion criteria. From the included studies, 44 tools were identified that measured a combination of physical, cognitive, sensory, motivational, and environmental barriers (n=19) or only cognition (n=13), vision (n=5), environmental factors (n=3), auditory (n=1), and motivational factors (n=1). The review also examined the psychometric properties of the identified tools and found that most of them had reported validity and reliability data. Several tools have demonstrated promise in assessing a combination of barriers with validity and reliability. These tools include the Self-Medication Assessment Tool (SMAT), ManageMed Screening (MMS), Self-Medication Risk Assessment Tool (RAT), HOME-Rx revised, and Medication Management Ability Assessment (MMAA). Conclusion This scoping review identified 44 validated tools to measure various challenges that older adults encounter with medication management. However, no tool measures all five barriers (physical, cognitive, sensory, motivational, and environmental) to medication-taking at home. Therefore, utilizing a combination of tools would be most appropriate to measure these different aspects comprehensively. Further research is needed to develop a new comprehensive tool that simultaneously measures various barriers to medication self-management.

Abstract Proton pump inhibitors (PPIs) are commonly used in cancer patients, but their impact on treatment outcomes in multiple myeloma (MM) patients remains unclear. This study investigated the association of PPI use with survival and adverse effects in MM patients across three randomized-control trials initiating daratumumab, lenalidomide, or bortezomib combination treatments. Cox proportional hazard analysis and logistic regression were employed to assess the associations with treatment outcomes, while adjusting for age, sex, weight, MM international staging system stage, ECOG-performance status, comorbidity count, and presence of gastrointestinal disorders. Pooled data involving 1804 patients revealed that 557 (32%) used PPIs at baseline. PPI use was independently associated with worse overall survival (adjusted HR [95% CI] 1.32 [1.08–1.62], P = 0.007) and grade ≥ 3 adverse events (adjusted OR [95% CI] 1.39 [1.03–1.88], P = 0.030). However, the association with progression-free survival did not reach statistical significance (adjusted HR [95% CI] 1.14 [0.97–1.33], P = 0.112). Findings were consistent across trials and treatment arms. PPI use was identified as a negative prognostic factor in MM patients, potentially enhancing clinical decisions regarding its use. Further research is needed to fully comprehend the impacts and safety of PPI use in MM patients.