Consultations about randomised controlled trials are shorter and less in-depth for socioeconomically disadvantaged patients compared to socioeconomically advantaged patients: qualitative analysis across three trials.

BACKGROUND: Patients from socioeconomically disadvantaged backgrounds are underserved in randomised controlled trials, yet they experience a much greater burden of disease compared with patients from socioeconomically advantaged areas. It is crucial to make trials more inclusive to ensure that treatments and interventions are safe and effective in real-world contexts. Improving how information about trials is verbally communicated is an unexplored strategy to make trials more inclusive. This study examined how trials are communicated verbally, comparing consultations involving patients from the most and least socioeconomically disadvantaged areas. METHODS: Secondary qualitative analysis of 55 trial consultation transcripts from 41 patients, sampled from 3 qualitative studies embedded in their respective UK multi-site, cancer-related randomised controlled trials. Patients living in the most and least socioeconomically disadvantaged areas, defined using English Indices of Multiple Deprivation decile scores, were purposively sampled. Analysis was largely thematic and drew on the constant comparison method. RESULTS: Recruiters communicated clinical uncertainty in a similar way for patients living in different socioeconomic areas. Consultations with disadvantaged patients were, on average, half the duration of those with advantaged patients, and tended to involve recruiters providing less in-depth explanations of trial concepts, used phrasing that softened trial arm risks, and described trial processes (e.g. randomisation) using informal or metaphorical phrasing. Disadvantaged and advantaged patients differed in the concerns they expressed; disadvantaged patients voiced fewer concerns and asked fewer questions but were also less likely to be invited to do so by recruiters. CONCLUSION: Interactions about trials unfolded in different ways between patients living in different socioeconomic areas, likely due to both patient- and recruiter-related factors. We present considerations for recruiters when discussing trials with patients from socioeconomically disadvantaged backgrounds, aimed at enhancing trial communication. Future research should examine disadvantaged patients' and recruiters' experiences of verbal trial communication to inform guidance that addresses the needs and preferences of underserved groups.

The indirect impact of infant negative emotionality on interparental conflict via perceptions of coparenting challenges: What prenatal resources mitigate this risk?

Research clearly demonstrates that conflictual interparental relationship dynamics can create a family context that contributes to child emotional insecurity and psychopathology. Significantly less research has examined familial factors that contribute to maladaptive conflict between parents. Scholars have alluded to the disruptive impacts of parenting a child with certain temperamental characteristics (e.g., negative emotionality). Yet, there is a lack of empirical research examining if and how child temperament contributes to later interparental conflict. Using an established multi-informant, multi-method sample of 150 families first assessed during pregnancy, and again when the child was 1, 2, and 3.5 years of age, the present study aimed to test an integrated conceptual model examining whether infants' negative emotionality assessed at age 1 predicts interparental conflict at age 3.5, as mediated through destructive coparenting dynamics in toddlerhood, and identifying prenatal protective factors mitigating this maladaptive pathway. Findings suggest that greater infant negative emotionality predicts worse interparental conflict management during preschool age by undermining the mother's (but not the father's) report of coparenting relationship quality during toddlerhood. However, these results were significant only to the extent that parents were lacking certain prenatal regulatory resources (i.e., low paternal self-compassion; less secure relationship between parents). Importantly, results point to the need for intervention and prevention efforts during pregnancy that might disrupt the deleterious impacts of parenting a child who is more reactive and prone to expressing negative emotions.

Evidence for within-species transition between drought response strategies in Nicotiana benthamiana.

Nicotiana benthamiana is predominantly distributed in arid habitats across northern Australia. However, none of six geographically isolated accessions shows obvious xerophytic morphological features. To investigate how these tender-looking plants withstand drought, we examined their responses to water deprivation, assessed phenotypic, physiological, and cellular responses, and analysed cuticular wax composition and wax biosynthesis gene expression profiles. Results showed that the Central Australia (CA) accession, globally known as a research tool, has evolved a drought escape strategy with early vigour, short life cycle, and weak, water loss-limiting responses. By contrast, a northern Queensland (NQ) accession responded to drought by slowing growth, inhibiting flowering, increasing leaf cuticle thickness, and altering cuticular wax composition. Under water stress, NQ increased the heat stability and water impermeability of its cuticle by extending the carbon backbone of cuticular long-chain alkanes from c. 25 to 33. This correlated with rapid upregulation of at least five wax biosynthesis genes. In CA, the alkane chain lengths (c. 25) and gene expression profiles remained largely unaltered. This study highlights complex genetic and environmental control over cuticle composition and provides evidence for divergence into at least two fundamentally different drought response strategies within the N. benthamiana species in < 1 million years.

Nature's Plastic Predators: A Comprehensive and Bibliometric Review of Plastivore Insects.

Unprecedented plastic production has resulted in over six billion tons of harmful waste. Certain insect taxa emerge as potential agents of plastic biodegradation. Through a comprehensive manual and bibliometric literature analysis, this review analyses and consolidates the growing literature related to insect-mediated plastic breakdown. Over 23 insect species, representing Coleoptera, Lepidoptera, and 4 other orders, have been identified for their capacity to consume plastic polymers. Natural and synthetic polymers exhibit high-level similarities in molecular structure and properties. Thus, in conjunction with comparative genomics studies, we link plastic-degrading enzymatic capabilities observed in certain insects to the exaptation of endogenous enzymes originally evolved for digesting lignin, cellulose, beeswax, keratin and chitin from their native dietary substrates. Further clarification is necessary to distinguish mineralisation from physicochemical fragmentation and to differentiate microbiome-mediated degradation from direct enzymatic reactions by insects. A bibliometric analysis of the exponentially growing body of literature showed that leading research is emerging from China and the USA. Analogies between natural and synthetic polymer's degradation pathways will inform engineering robust enzymes for practical plastic bioremediation applications. By aggregating, analysing, and interpreting published insights, this review consolidates our mechanistic understanding of insects as a potential natural solution to the escalating plastic waste crisis.

A population-based analysis of the management of symptoms of depression among patients with stage IV non-small cell lung cancer (NSCLC) in Ontario, Canada.

PURPOSE: Patients with lung cancer can experience significant psychological morbidities including depression. We characterize patterns and factors associated with interventions for symptoms of depression in stage IV non-small cell lung cancer (NSCLC). METHODS: We conducted a population-based cohort study using health services administrative data in Ontario, Canada of stage IV NSCLC diagnosed from January 2007 to September 2018. A positive symptom of depression score was defined by reporting at least one ESAS (Edmonton Symptom Assessment System) depression score ≥ 2 following diagnosis until the end of follow-up (September 2019). Patient factors included age, sex, comorbidity burden, rurality of residence, and neighbourhood income quintile. Interventions included psychiatry assessment, psychology referral, social work referral and anti-depressant medical therapy (for patients ≥ 65 years with universal drug coverage). Multivariable modified Poisson regression models were used to examine the association between patient factors and intervention use for patients who reported symptoms of depression. RESULTS: In the cohort of 13,159 patients with stage IV NSCLC lung cancer, symptoms of depression were prevalent (71.4%, n = 9,397). Patients who reported symptoms of depression were more likely to receive psychiatry assessment/psychology referral (7.8% vs 3.5%; SD [standardized difference] 0.19), social work referral (17.4% vs 11.9%; SD 0.16) and anti-depressant prescriptions (23.8% vs 13.8%; SD 0.26) when compared to patients who did not report symptoms of depression respectively. In multivariable analyses, older patients were less likely to receive any intervention. Females were more likely to obtain a psychiatry assessment/psychology referral or social work referral. In addition, patients from non-major urban or rural residences were less likely to receive psychiatry assessment/psychology referral or social work referral, however patients from rural residences were more likely to be prescribed anti-depressants. CONCLUSIONS: There is high prevalence of symptoms of depression in stage IV NSCLC. We identify patient populations, including older patients and rural patients, who are less likely to receive interventions that will help identifying and screening for symptoms of depression.

Quantitative ultrasound radiomics guided adaptive neoadjuvant chemotherapy in breast cancer: early results from a randomized feasibility study.

Background: In patients with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy (NAC), quantitative ultrasound (QUS) radiomics can predict final responses early within 4 of 16-18 weeks of treatment. The current study was planned to study the feasibility of a QUS-radiomics model-guided adaptive chemotherapy. Methods: The phase 2 open-label randomized controlled trial included patients with LABC planned for NAC. Patients were randomly allocated in 1:1 ratio to a standard arm or experimental arm stratified by hormonal receptor status. All patients were planned for standard anthracycline and taxane-based NAC as decided by their medical oncologist. Patients underwent QUS imaging using a clinical ultrasound device before the initiation of NAC and after the 1st and 4th weeks of treatment. A support vector machine-based radiomics model developed from an earlier cohort of patients was used to predict treatment response at the 4th week of NAC. In the standard arm, patients continued to receive planned chemotherapy with the treating oncologists blinded to results. In the experimental arm, the QUS-based prediction was conveyed to the responsible oncologist, and any changes to the planned chemotherapy for predicted non-responders were made by the responsible oncologist. All patients underwent surgery following NAC, and the final response was evaluated based on histopathological examination. Results: Between June 2018 and July 2021, 60 patients were accrued in the study arm, with 28 patients in each arm available for final analysis. In patients without a change in chemotherapy regimen (53 of 56 patients total), the QUS-radiomics model at week 4 of NAC that was used demonstrated an accuracy of 97%, respectively, in predicting the final treatment response. Seven patients were predicted to be non-responders (observational arm (n=2), experimental arm (n=5)). Three of 5 non-responders in the experimental arm had chemotherapy regimens adapted with an early initiation of taxane therapy or chemotherapy intensification, or early surgery and ended up as responders on final evaluation. Conclusion: The study demonstrates the feasibility of QUS-radiomics adapted guided NAC for patients with breast cancer. The ability of a QUS-based model in the early prediction of treatment response was prospectively validated in the current study. Clinical trial registration: clinicaltrials.gov, ID NCT04050228.

The Impact of COVID-19 on Breast Cancer Care: A Qualitative Analysis of Surgeons' Perspectives.

INTRODUCTION: While studies have documented delays in breast cancer (BC) care during the COVID-19 pandemic due to healthcare restrictions, there have been no studies on the experiences, and, particularly, the challenges with providing care faced by breast surgeons during this unprecedented time. This paper aims to understand the perspectives of breast surgeons regarding the impact of the COVID-19 pandemic on BC care. METHODS: We used purposeful and snowball sampling to identify breast surgeons in Ontario, Canada. One-on-one qualitative semi-structured interviews were conducted exploring the impact of the pandemic on BC treatment, psychosocial well-being of patients and providers, and the future state of BC care. Audio-recorded interviews were transcribed verbatim and analyzed using Thematic Analysis. RESULTS: A total of 10 breast surgeons (5 community and 5 academic) were interviewed. Breast surgeons reported that the pandemic led to increased multidisciplinary collaboration and innovations in delivery of BC surgery (e.g., increased use of regional anesthesia). Multiple surgeons identified that the pandemic created disparities in BC care based geographic location and that existing disparities in care based on ethnicity or marginalization were exacerbated. Last, surgeons identified that virtual care improved, but also created some challenges to how BC care was delivered, with many hoping for this to be continued after the pandemic was over. CONCLUSIONS: In this study, breast surgeons identified unique challenges and solutions to BC care delivery during the pandemic. Concerns regarding disparities in care based on geographic location and marginalized patients require further study to improve future BC care.

Surveillance evaluations in patients with stage I, II, III, or resectable IV melanoma who were treated with curative intent: A systematic review.

PURPOSE: Appropriate surveillance of patients with melanoma treated with curative intent is vital to improve patient outcomes. A systematic review was conducted to capture locoregional recurrence and metastatic disease, and to evaluate the effectiveness of various surveillance strategies. METHODS: MEDLINE, EMBASE, PubMed, Cochrane Database of Systematic Reviews, and National Cancer Institute Clinical Trials Database were searched. Randomized controlled trials (RCTs) and comparative studies reporting at least one patient-related outcome were included. Exclusion criteria included: published in non-English or recruited >20 % or an uncertain percentage of non-target patients without conducting a subgroup analysis for the target patients. This review was registered at PROSPERO (CRD42021246482). RESULTS: Among 17,978 publications from the literature search, one RCT and five non-randomized comparative studies were included and comprised 4016 patients. The aggregate evidence certainty was low for the RCT and very low for the comparative studies, as assessed by the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. For patients with stage IA-IIC melanoma, a reduced follow-up schedule with clinical follow-up strategies alone may be safe and cost-effective. For stage IIC-IIIC patients, at least two serial PET/CT or whole-body CT and brain MRI imaging within a median follow-up of 31.2 months may detect 50 % of recurrences that lead to additional management, such as surgery. PET/CT may have a higher positive predictive value and lower false positive rate compared with CT alone in detecting recurrence in stage I-III patients. CONCLUSION: Surveillance protocols should be based on individual risk of recurrence and established best practices when formulating follow-up strategies, as suggested by the studies reviewed. Future high-quality studies are needed to clarify the frequency of imaging follow-up strategies, especially in patients with high-risk stage II melanoma.

Neoadjuvant chemotherapy for triple-negative and Her2 +ve breast cancer: striving for the standard of care.

PURPOSE: Neoadjuvant chemotherapy (NAC) for triple-negative (TN) and Her2-positive (HER2) breast cancers is supported by international guidelines as it can decrease extent of surgery, provide prognostic information, and allow response-driven adjuvant therapies. Our goal was to describe practice patterns for patients with TN and HER2-positive breast cancer and identify the factors associated with the receipt of NAC versus surgery as initial treatment. METHODS: A retrospective population-based cohort study of adult women diagnosed with stage I-III TN or HER2-positive breast cancer (2012-2020) in Ontario was completed using linked administrative datasets. The primary outcome was NAC as first treatment. The association between NAC and patient, tumor, and practice-related factors was examined using multivariable logistic regression models. RESULTS: Of 14,653 patients included, 23.9% (n = 3500) underwent NAC as first treatment. Patients who underwent NAC were more likely to be younger and have larger tumors, node-positive disease, and stage 3 disease. Of patients who underwent surgery first, 8.8% were seen by a medical oncologist prior to surgery. On multivariable analysis, increasing tumor size (T2 vs T1/T0: 2.75 (2.31-3.28)) and node-positive (N1 vs N0: OR 3.54 (2.92-4.30)) disease were both associated increased odds of receiving NAC. CONCLUSION: A considerable proportion of patients with TN and HER2-positive breast cancer do not receive NAC as first treatment. Of those, most were not assessed by both a surgeon and medical oncologist prior to initiating therapy. This points toward potential gaps in multidisciplinary assessment and disparities in receipt of guideline-concordant care.

Bioactive metabolites of Asparagopsis stabilized in canola oil completely suppress methane emissions in beef cattle fed a feedlot diet.

Asparagopsis taxiformis (Asparagopsis) has been shown to be highly efficacious at inhibiting the production of methane (CH4) in ruminants. To date, Asparagopsis has been primarily produced as a dietary supplement by freeze-drying to retain the volatile bioactive compound bromoform (CHBr3) in the product. Steeping of Asparagopsis bioactive compounds into a vegetable oil carrier (Asp-Oil) is an alternative method of stabilizing Asparagopsis as a ruminant feed additive. A dose-response experimental design used 3 Asp-Oil-canola oil blends, low, medium, and high Asp-Oil which provided 17, 34, and 51 mg Asparagopsis derived CHBr3/kg dry matter intake (DMI), respectively (in addition to a zero CHBr3 canola oil control), in a tempered-barley based feedlot finisher diet, fed for 59 d to 20 Angus heifers (five replicates per treatment). On four occasions, live weight was measured and CH4 emissions were quantified in respiration chambers, and blood, rumen fluid, and fecal samples were collected. At the end of the experiment, all animals were slaughtered, with carcasses graded, and samples of meat and edible offal collected for testing of consumer sensory qualities and residues of CHBr3, bromide, and iodide. All Asp-Oil treatments reduced CH4 yield (g CH4/kg DMI, P = 0.008) from control levels, with the low, medium, and high Asp-Oil achieving 64%, 98%, and 99% reduction, respectively. Dissolved hydrogen increased linearly with increasing Asp-Oil inclusion, by more than 17-fold in the high Asp-Oil group (P = 0.017). There was no effect of Asp-Oil treatment on rumen temperature, pH, reduction potential, volatile fatty acid and ammonia production, rumen pathology, and histopathology (P > 0.10). There were no differences in animal production and carcass parameters (P > 0.10). There was no detectable CHBr3 in feces or any carcass samples (P > 0.10), and iodide and bromide residues in kidneys were at levels unlikely to lead to consumers exceeding recommended maximum intakes. Overall, Asp-Oil was found to be safe for animals and consumers of meat, and effective at reducing CH4 emissions and yield by up to 99% within the range of inclusion levels tested.

Red seaweed, Asparagopsis taxiformis (Asparagopsis), has been shown to be highly effective at inhibiting the production of methane (CH4) in ruminants. An alternative to feeding whole, freeze-dried Asparagopsis is steeping the biomass in vegetable oil to stabilize the bioactive compounds (Asp-Oil) and feeding Asp-Oil to ruminants as a component of their dietary intake. This experiment measured the CH4 reduction potential and safety of Asp-Oil in a trial with 20 Angus heifers, fed iso-fat feedlot diets containing one of the three levels of Asp-Oil, or a control oil. Compared to the control, bromoform inclusion levels of 17, 34, and 51 mg/kg of dry matter (DM; low, medium, high) reduced CH4 yield (g CH4/kg DM intake) by 64%, 98%, and 99%, respectively. There were no effects on animal production or carcass characteristics. There were no impacts on animal health, welfare, or rumen function. Carcasses were safe for human consumption, and there was no bromoform detected in any carcass samples. Overall, Asp-Oil was found to effectively reduce CH4 emissions and is safe for animals and consumers of meat and edible offal.

A scoping assessment of dental services at designated head and neck cancer centres in Ontario, Canada.

BACKGROUND: Dentists serve a crucial role in managing treatment complications for patients with head and neck cancer, including post-radiation caries and oral infection. To date, dental services for head and neck cancer patients in Ontario, Canada have not been well characterized and considerable disparities in allocation, availability, and funding are thought to exist. The current study aims to describe and assess the provision of dental services for head and neck cancer patients in Ontario. METHODS: A mixed methods scoping assessment was conducted. A purposive sample of dentist-in-chiefs at each of Ontario's 9 designated head and neck cancer centres (tertiary centres which meet provincially-set quality and safety standards) was invited to participate. Participants completed a 36-item online survey and 60-minute semi-structured interview which explored perceptions of dental services for head and neck cancer patients at their respective centres, including strengths, gaps, and inequities. If a centre did not have a dentist-in-chief, an alternative stakeholder who was knowledgeable on that centre's dental services participated instead. Thematic analysis of the interview data was completed using a mixed deductive-inductive approach. RESULTS: Survey questionnaires were completed at 7 of 9 designated centres. A publicly funded dental clinic was present at 5 centres, but only 2 centres provided automatic dental assessment for all patients. Survey data from 2 centres were not captured due to these centres' lack of active dental services. Qualitative interviews were conducted at 9 of 9 designated centres and elicited 3 themes: (1) lack of financial resources; (2) heterogeneity in dentistry care provision; and (3) gaps in the continuity of care. Participants noted concerning under-resourcing and limitations/restrictions in funding for dental services across Ontario, resulting in worse health outcomes for vulnerable patients. Extensive advocacy efforts by champions of dental services who have sought to mitigate current disparities in dentistry care were also described. CONCLUSIONS: Inequities exist in the provision of dental services for head and neck cancer patients in Ontario. Data from the current study will broaden the foundation for evidence-based decision-making on the allocation and funding of dental services by government health care agencies.

Cost-Effectiveness of Extracorporeal Photopheresis in Patients With Chronic Graft-vs-Host Disease.

Background: The mainstay first-line therapy for chronic graft-vs-host disease (cGVHD) is corticosteroids; however, for steroid-refractory patients, there is a distinct lack of cost-effective or efficacious treatment. The aim of this study was to assess the cost-effectiveness of extracorporeal photopheresis (ECP) compared with standard-of-care therapies for the treatment of cGVHD in Australia. The study formed part of an application to the Australian Government to reimburse ECP for these patients. Methods: A cost-utility analysis was conducted comparing ECP to standard of care, which modeled the response to treatment and disease progression of cGVHD patients in Australia. Mycophenolate, tacrolimus, and cyclosporin comprised second-line standard of care based on a survey of Australian clinicians. Health states in the model included treatment response, disease progression, and death. Transition probabilities were obtained from Australian-specific registry data and randomized controlled evidence. Quality-of-life values were applied based on treatment response. The analysis considered costs of second-line treatment and disease management including immunosuppressants, hospitalizations and subsequent therapy. Disease-specific mortality was calculated for treatment response and progression. Results: Over a 10-year time horizon, ECP resulted in an average cost reduction of $23 999 and an incremental improvement of 1.10 quality-adjusted life-years per patient compared with standard of care. The sensitivity analysis demonstrated robustness over a range of plausible scenarios. Conclusion: This analysis demonstrates that ECP improves quality of life, minimizes the harms associated with immunosuppressant therapy, and is a highly cost-effective option for steroid-refractory cGVHD patients in Australia. Based in part on this analysis, ECP was listed on the Medicare Benefits Schedule for public reimbursement.

How to Partner With Persons Living With Mental Health Conditions: A Guide for Meaningful Simulation Cocreation.

SUMMARY STATEMENT: Screen-based simulation is an effective educational strategy that can enhance health care students' engagement with content and critical thinking across various topics, including mental health. To create relevant and realistic simulations, best-practice guidelines recommend the involvement of experts in the development process. We collaborated with persons with lived experience and community partners to cocreate a mental health-focused screen-based simulation. Cocreating meant establishing a nonhierarchical partnership, with shared decision-making from start to finish.In this article, we present 8 principles developed to guide our cocreation with persons with lived experience: person-centeredness, trauma-informed approaches and ethical guidance, supportive environment, two-way partnership, mutual respect, choice and flexibility, open communication, and room to grow. These principles provide practical guidance for educators seeking to engage the expertise of persons who have been historically disadvantaged in society. By sharing these principles, we strive to contribute to a more equitable process in simulation development and promote meaningful, respectful, and safer collaborations.

Targeted screening of inflammatory mediators in spontaneous degenerative disc disease in dogs reveals an upregulation of the tumor necrosis superfamily.

Background: The regulation of inflammatory mediators in the degenerating intervertebral disc (IVD) and corresponding ligamentum flavum (LF) is a topic of emerging interest. The study aimed to investigate the expression of a broad array of inflammatory mediators in the degenerated LF and IVD using a dog model of spontaneous degenerative disc disease (DDD) to determine potential treatment targets. Methods: LF and IVD tissues were collected from 22 normal dogs (Pfirrmann grades I and II) and 18 dogs affected by DDD (Pfirrmann grades III and IV). A qPCR gene array was used to investigate the expression of 80 inflammatory genes for LF and IVD tissues, whereafter targets of interest were investigated in additional tissue samples using qPCR, western blot (WB), and immunohistochemistry. Results: Tumor necrosis factor superfamily (TNFSF) signaling was identified as a regulated pathway in DDD, based on the significant regulation (n-fold ± SD) of various TNFSF members in the degenerated IVD, including nerve growth factor (NGF; -8 ± 10), CD40LG (464 ± 442), CD70 (341 ± 336), TNFSF Ligand 10 (9 ± 8), and RANKL/TNFSF Ligand 11 (85 ± 74). In contrast, TNFSF genes were not significantly affected in the degenerated LF compared to the control LF. Protein expression of NGF (WB) was significantly upregulated in both the degenerated LF (4.4 ± 0.5) and IVD (11.3 ± 5.6) compared to the control group. RANKL immunopositivity was significantly upregulated in advanced stages of degeneration (Thompson grades IV and V) in the nucleus pulposus and annulus fibrosus of the IVD, but not in the LF. Conclusions: DDD involves a significant upregulation of various TNFSF members, with tissue-specific expression profiles in LF and IVD tissues. The differential involvement of TNFSF members within multiple spinal tissues from the same individual provides new insights into the inflammatory processes involved in DDD and may provide a basis to formulate hypotheses for the determination of potential treatment targets.

Age of onset of obsessive-compulsive disorder differentially affects white matter microstructure.

Previous diffusion MRI studies have reported mixed findings on white matter microstructure alterations in obsessive-compulsive disorder (OCD), likely due to variation in demographic and clinical characteristics, scanning methods, and underpowered samples. The OCD global study was created across five international sites to overcome these challenges by harmonizing data collection to identify consistent brain signatures of OCD that are reproducible and generalizable. Single-shell diffusion measures (e.g., fractional anisotropy), multi-shell Neurite Orientation Dispersion and Density Imaging (NODDI) and fixel-based measures, were extracted from skeletonized white matter tracts in 260 medication-free adults with OCD and 252 healthy controls. We additionally performed structural connectome analysis. We compared cases with controls and cases with early (<18) versus late (18+) OCD onset using mixed-model and Bayesian multilevel analysis. Compared with healthy controls, adult OCD individuals showed higher fiber density in the sagittal stratum (B[SE] = 0.10[0.05], P = 0.04) and credible evidence for higher fiber density in several other tracts. When comparing early (n = 145) and late-onset (n = 114) cases, converging evidence showed lower integrity of the posterior thalamic radiation -particularly radial diffusivity (B[SE] = 0.28[0.12], P = 0.03)-and lower global efficiency of the structural connectome (B[SE] = 15.3[6.6], P = 0.03) in late-onset cases. Post-hoc analyses indicated divergent direction of effects of the two OCD groups compared to healthy controls. Age of OCD onset differentially affects the integrity of thalamo-parietal/occipital tracts and the efficiency of the structural brain network. These results lend further support for the role of the thalamus and its afferent fibers and visual attentional processes in the pathophysiology of OCD.

A Feasibility Randomized Controlled Trial of Prehabilitation During Neoadjuvant Chemotherapy for Women with Breast Cancer: A Mixed Methods Study.

BACKGROUND: Limited data exist regarding the role of multimodal prehabilitation during neoadjuvant chemotherapy (NACT) for breast cancer. Determining large trial feasibility and identifying signals of prehabilitation benefit are needed. PATIENTS AND METHODS: We conducted a randomized controlled feasibility trial of multimodal prehabilitation versus usual care during NACT among women diagnosed with non-metastatic breast cancer. Intervention participants received an individualized exercise program, dietetic support, and stress management counseling during NACT. The trial assessed feasibility via rates of recruitment, attrition, adherence, and study-related adverse events. Physical fitness (Six Minute Walk Test, grip strength, anthropometrics) and patient-reported outcomes were assessed at baseline, after NACT completion, and 6 months after surgery as exploratory outcomes, and analyzed using linear mixed effects models. Qualitative data were collected from a subsample to understand feasibility and acceptability of prehabilitation. RESULTS: A total of 72 participants were enrolled from the 123 eligible patients (recruitment rate of 53%). There was a 13% attrition rate and no intervention-related adverse events. Participants in the prehabilitation group had better 6-min walk distance at the post-chemotherapy timepoint [between group difference of 49.43 m, 95% confidence interval (CI) - 118.1, 19.2] and at the post-surgery timepoint (27.3, 95% CI -96.8, 42.2) compared with the control group. Prehabilitation participants reported better quality of life, less fatigue, and improved physical activity levels compared with usual care participants. Interviews revealed that the intervention had a positive impact on the treatment experience. CONCLUSIONS: This study demonstrated feasibility and improvement in physical and psychosocial outcomes. Larger trials assessing intervention efficacy to confirm indications of prehabilitation benefit are warranted.

Enhancing Symptom Screening and Patient Education Among Patients with Metastatic Lung Cancer: a Qualitative Analysis.

We explored perspectives of patients with metastatic non-small cell lung cancer (mNSCLC) on symptom screening and population-level patient-reported outcome (PRO) data regarding common symptom trajectories in the year after diagnosis. A qualitative study of patients with mNSCLC was conducted at a Canadian tertiary cancer centre. English-speaking patients diagnosed ≥ 6 months prior to study invitation were recruited, and semi-structured one-on-one interviews were conducted. Patient and treatment characteristics were obtained via chart review. Anonymized interview transcripts underwent deductive-inductive coding and thematic content analysis. Among ten participants (5 (50%) females; median (range) age, 68 (56-77) years; median (range) time since diagnosis, 28.5 (6-72) months; 6 (60%) with smoking histories), six themes were identified in total. Two themes were identified regarding symptom screening: (1) screening is useful for symptom self-monitoring and disclosure to the healthcare team, (2) screening of additional quality-of-life (QOL) domains (smoking-related stigma, sexual dysfunction, and financial toxicity) is desired. Four themes were identified regarding population-level symptom trajectory PRO data: (1) data provide reassurance and motivation to engage in symptom self-management, (2) data should be disclosed after an oncologic treatment plan is developed, (3) data should be communicated via in-person discussion with accompanying patient-education resources, and (4) communication of data should include reassurance about symptom stabilization, acknowledgement of variability in patient experience, and strategies for symptom self-management. The themes and recommendations derived from the patient experience with mNSCLC provide guidance for enhanced symptom screening and utilization of population-level symptom trajectory data for patient education.

Defining Standards for Hepatopancreatobiliary Cancer Surgery in Ontario, Canada: A Population-Based Cohort Study of Clinical Outcomes.

BACKGROUND: In 2006, Cancer Care Ontario created Surgical Oncology Standards for the delivery of hepatopancreatobiliary (HPB) surgery including hepatectomy and pancreaticoduodenectomy (PD). Our objective was to identify the impact of standardization on outcomes after HPB surgery in Ontario, Canada. STUDY DESIGN: This study was a population-level analysis of patients undergoing hepatectomy or PD (2003 to 2019). Logistic regression models were used to compare 30- and 90-day mortality and length of stay (LOS) before (2003 to 2006), during (2007 to 2011), and after (2012 to 2019) standardization. Interrupted time series models were used to co-analyze secular trends. RESULTS: A total of 7,904 hepatectomies and 5,238 PDs were performed. More than 80% of all cases were performed at a designated center (DC) before standardization. This increased to >98% in the poststandardization era. Median volumes at DCs increased from 55 to 67 hepatectomies/year and from 22 to 50 PDs/year over time. In addition, 30-day mortality after hepatectomy was 2.6% before standardization and 2.3% after standardization (p = 0.9); 30-day mortality after PD was 3.6% before standardization and 2.4% after standardization (p = 0.1). Multivariable analyses revealed a significant difference in 90-day mortality following PD poststandardization (4.3% vs 6.3%; adjusted odds ratio, 0.7; p = 0.03). Median LOS was shorter for hepatectomy (6 days vs 8 days) and PD (9 days vs 14 days; p < 0.0001) after standardization. Immediate and late effects on mortality and LOS were likely attributable to secular trends, which predated standardization. CONCLUSIONS: Standardization was associated with a higher volume of hepatectomy and PDs with further concentration of care at DCs. Pre-existing quality initiatives may have attenuated the effect of standardization on quality outcomes. Our data highlight the merits of a multifaceted provincial system for enabling consistent access to high quality HPB care throughout a region of 15 million people over a 16-year period.