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Abstract Background The current study examined potential risk factors for experiencing a decline on the interRAI Cognitive Performance Scale (CPS). Methods This was a retrospective cohort study using secondary data collected with the Resident Assessment Instrument for Home Care (RAI-HC) for all assessments completed in Canada between 2001 and 2020. Eligible home care clients included individuals 65+, with at least two assessments completed within 12 months, and who had a CPS score of zero at baseline (n = 146,187). A decline on the CPS was defined as any increase (i.e., worsening) on the CPS score between the two assessments. Results The mean age of the sample was 80.6 years (standard deviation = 7.7), 67.9% were female and 44.5% were widowed. At the time of the second assessment, 25.2% experienced a decline on their CPS score. In the final multivariate model, age, having a diagnosis of Alzheimer’s dementia/other type of dementia, physical inactivity, and having a caregiver at risk of experiencing burden were the most significant predictors of experiencing the outcome. Conclusions Roughly one-quarter of Canadian home care clients experienced a cognitive decline, over an average of seven months. Since there are some modifiable risk factors for this outcome, it is important to identify and flag these factors as early as possible. Early identification of modifiable risk factors allows clinicians to create care plans that can optimize the well-being of the client and their family.

Objective To identify the types of conditions reported in peer-reviewed literature that result in chronic musculoskeletal lower limb pain in children and adolescents and explore the alignment of these conditions with the chronic pain reporting codes indexed in the International Classification of Diseases 11th Revision (ICD-11).Design This scoping review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data sources Five electronic databases were searched (Medline, EMBASE, PsycINFO, CINAHL and the Cochrane Library).Eligibility criteria Articles involving children and adolescents under 18 years and reporting on chronic musculoskeletal pain of the lower limb were included.Data extraction and synthesis We assigned an ICD-11 code to each condition based on details reported in the study. We recorded whether any of the presenting conditions were linked to an ICD-11 chronic pain manifestation code.Results From 12 343 records, 418 papers were included. There were 124 unique conditions associated with chronic lower limb pain, the most commonly reported being chronic widespread musculoskeletal pain (24 studies) and juvenile idiopathic arthritis (26 studies). Only 11.1% of presenting conditions were linked to an ICD-11 chronic pain manifestation code.Conclusion Most presenting conditions associated with chronic pain in the lower limb do not have a chronic pain manifestation code in the new global standard for recording health information. This means chronic pain associated with common lower limb conditions may remain invisible in global statistics.

Introduction: Breast cancer treatment includes neoadjuvant chemotherapy offered to patients with aggressive subtypes and locally advanced breast cancer. Black women receive neoadjuvant chemotherapy more frequently as they present more advanced stage tumors and triple negative subtype. Non-Hispanic Black women have the greatest prevalence of obesity in most states. Patients with higher body mass index (BMI) have lower rates of chemotherapy response. Whether obesity is a confounding factor requires investigation.Methods: A retrospective cohort study of patients diagnosed with non-metastatic breast cancer who completed neoadjuvant chemotherapy and had surgery at The Ohio State University Comprehensive Cancer Center between January 1 2005 and December 31 2019, was conducted. Demographic characteristics were compared using Pearson’s chi-square test, or Wilcoxon rank-sum test. Logistic regression models were used to assess associations between pathologic response and age, race, BMI, menopausal status, and insurance status.Results: More Black women had high grade tumors, triple negative advanced stage disease, and higher BMI. Race and BMI were not significant predictors of poor pathologic complete response, however patients aged

Introduction Brace treatment is common to address radiological dysplasia in infants with developmental dysplasia of the hip (DDH); however, it is unclear whether bracing provides significant benefit above careful observation by ultrasound. If observation alone is non-inferior to bracing for radiological dysplasia, unnecessary treatment may be avoided. Therefore, the purpose of this study is to determine whether observation is non-inferior to bracing for infants with radiological dysplasia.Methods and analysis This will be a multicentre, global, randomised, non-inferiority trial performed under the auspices of a global prospective registry for infants and children diagnosed with DDH. Patients will be included if they present with radiological dysplasia (centred hip, alpha angle 43–60°, percent femoral head coverage greater than 35% measured on ultrasound) of a clinically stable hip under 3 months old. Patients will be excluded if they present with clinical hip instability, have received prior treatment or have known/suspected neuromuscular, collagen, chromosomal or lower-extremity congenital abnormalities or syndromic-associated hip abnormalities. Patients will be enrolled and randomised to undergo observation alone or brace treatment with a Pavlik harness for a minimum of 6 weeks. Follow-up visits will occur at 6 weeks, 1 year and 2 years post-enrolment. The primary outcome will be the norm-referenced acetabular index measured on the 2-year radiograph with a 3° non-inferiority margin. A total of 514 patients will be included.The study is anticipated to start in April 2024 and end in September 2028.The primary outcome will be compared between arms with a mixed-effects model with a random intercept for study centre, and a single covariate for the treatment group. If the lower bound of the 95% CI lies within 3° of the mean, we will treat this as evidence for non-inferiority.Ethics and dissemination Ethics approval has been obtained from the lead site’s ethics board (University of British Columbia, Children’s and Women’s Research Ethics Board). Ethics approval will be obtained from the local ethics committees or institutional review boards at each institution prior to patient enrolment. It is intended that the results of this study shall be published in peer-reviewed journals and presented at suitable conferences.Trial registration number NCT05869851.

Abstract Background The optimal adjuvant endocrine therapy (ET) in hormone receptor positive (HR+) and human epidermal growth factor receptor 2 positive (HER2+) premenopausal breast cancer (BC) remains unclear. Moreover, the benefit and clinical indications of ovarian suppression (OS) is poorly elucidated. We described real‐world patterns surrounding choice of ET and clinicopathologic features which predicted treatment with OS in a contemporary cohort of premenopausal women with HR+/HER2+ BC. Methods This retrospective analysis included premenopausal patients with nonmetastatic HR+/HER2+ BC from the CancerLinQ Discovery database from January 2010 to May 2020. Women were less than 50 years and received chemotherapy, anti‐HER2 therapy, and ET. They were categorized into 1 of 4 groups based on type of ET prescribed at initiation: aromatase inhibitor (AI) + OS, OS, tamoxifen + OS, or tamoxifen. Multivariable logistic regression assessed associations between clinicopathologic features and OS use. Results Out of 360,540 patients with BC, 937 were included. The majority (n = 818, 87%) were prescribed tamoxifen, whereas 4 (0.4%), 50 (5.3%), and 65 (6.9%) received OS, tamoxifen + OS and AI + OS, respectively. No clinicopathologic features predicted OS use apart from age; patients

Abstract Background To develop and validate a prediction tool, or nomogram, for the risk of a decline in cognitive performance based on the interRAI Cognitive Performance Scale (CPS). Methods Retrospective, population-based, cohort study using Canadian Resident Assessment Instrument for Home Care (RAI-HC) data, collected between 2010 and 2018. Eligible home care clients, aged 18+, with at least two assessments were selected randomly for model derivation (75%) and validation (25%). All clients had a CPS score of zero (intact) or one (borderline intact) on intake into the home care program, out of a possible score of six. All individuals had to remain as home care recipients for the six months observation window in order to be included in the analysis. The primary outcome was any degree of worsening (i.e., increase) on the CPS score within six months. Using the derivation cohort, we developed a multivariable logistic regression model to predict the risk of a deterioration in the CPS score. Model performance was assessed on the validation cohort using discrimination and calibration plots. Results We identified 39,292 eligible home care clients, with a median age of 79.0 years, 62.3% were female, 38.8% were married and 38.6% lived alone. On average, 30.3% experienced a worsening on the CPS score within the six-month window (i.e., a change from 0 or 1 to 2, 3, 4, 5, or 6). The final model had good discrimination (c-statistic of 0.65), with excellent calibration. Conclusions The model accurately predicted the risk of deterioration on the CPS score over six months among home care clients. This type of predictive model may provide useful information to support decisions for home care clinicians who use interRAI data internationally.

Background: Developmental Dysplasia of the Hip (DDH) describes a spectrum of abnormalities that impact the normal function of the joint. These abnormalities are detectable during infancy using physical assessment, universal ultrasound, or a combination of both. In Australia, child health nurses predominantly screen for this disease using physical assessment. The aim of this study was to determine if child health nurses can accurately screen for DDH using physical assessment. Methods: This Australian study estimated the accuracy and utility of child health nurses using physical assessment to screen for DDH by comparing it to a handheld ultrasound device. Results: This study (N = 44) concluded that using a point prevalence study design, child health nurses in Australia are unable to accurately assess for DDH in infants using physical assessment; overall, clinicians had 50.5% sensitivity (95% CI, 15.7 to 84.3), a specificity of 75.0% (95% CI, 57.8 to 87.9), and 71.3% accuracy (95% CI, 55.6 to 83.9). Conclusion: This study suggests that child health nurses cannot screen for DDH using physical assessment. Understanding education, experience and what assessments are used suggests that the utility of nurses performing DDH screening requires further investigation.

Abstract Introduction The immunomodulatory impact of corticosteroids and concurrent chemotherapy is poorly understood within triple-negative breast cancer (TNBC). On a biochemical level, steroids have been linked to the signaling of chemotherapy-resistant pathways. However, on a clinical level, steroids play an essential role in chemotherapy tolerance through the prevention of chemotherapy-induced nausea and vomiting (CINV) and hypersensitivity reactions. Given these conflicting roles, we wanted to evaluate this interplay more rigorously in the context of early-stage TNBC. Methods We performed a retrospective analysis of patients with operable TNBC who received neoadjuvant chemotherapy (NAC) between January 2012 and November 2018, with the primary goal of examining the dose-dependent relationship between pathological complete response (pCR) rates and corticosteroid use. Secondary endpoints included the impact of steroid dosing on overall survival (OS) and recurrence-free survival (RFS), along with a breakdown in pCR rates based on steroid doses provided during each chemotherapy phase. Further adjusted analyses were performed based on patient age, diabetic status, and anatomical stage. Finally, we explored the relationship between tumor-infiltrating lymphocytes (TILs) seen on tissue samples at baseline and dexamethasone doses in terms of pCR rates. Results In total, of the 174 patients screened within this study period, 116 met full eligibility criteria. Of these eligible patients, all were female, with a median age of 51.5 years (27.0 to 74.0) and a mean body mass index (BMI) of 29.7 [standard deviation (SD) 7.04]. The majority were nondiabetic (80.2%). For cancer stage, 69.8% (n = 81) had stage 2 breast cancer. We found no statistically significant association between pCR rates and dexamethasone use, both in terms of the total dose (p = 0.55) and mean dose per NAC cycle (p = 0.74). Similarly, no difference was noted when adjusting for diabetic status, metformin use, or age at diagnosis, regardless of the total steroid dose provided (p = 0.72) or mean dose per cycle (p = 0.49). No meaningful changes to pCR rate were seen with higher mean or higher total steroid doses during the paclitaxel (T) phase (adjusted p = 0.16 and p = 0.76, respectively) or doxorubicin and cyclophosphamide (AC) phase (adjusted p = 0.83 and p = 0.77, respectively). Furthermore, we found no clinically significant association between dexamethasone dose and either RFS (p = 0.45) or OS (p = 0.89). Of the 56 patients who had available pre-treatment biopsy tissue samples, 27 achieved pCR, with higher TILs at baseline being associated with higher pCR rates, regardless of the mean dexamethasone dose used. Conclusion Our findings demonstrate that dexamethasone has no clinically significant impact on pCR, RFS, or OS when given concurrently with NAC in patients with curative TNBC, regardless of diabetic status.

Abstract Background The Respiratory Infection Intensity and Impact Questionnaire (RiiQ™) is a patient-reported outcome measure designed to assess symptoms and impacts of respiratory syncytial virus (RSV) infection. This study evaluated the construct validity, reliability, and responsiveness of the RiiQ™ Respiratory and Systemic Symptoms Scale scores. Methods Prospective data were analyzed from a total of 1795 participants, including from non-hospitalized patients with acute respiratory infection (ARI) and no coinfections enrolled in a Phase 2b RSV vaccine study (RSV-positive: n = 60; RSV-negative: n = 1615), and two observational studies of patients hospitalized with RSV (n = 20; n = 100). Descriptive statistics, confirmatory factor analysis (CFA), test–retest intraclass correlation coefficients (ICCs), construct validity correlations (between a clinician-assessed clinical questionnaire and the RiiQ™ symptoms scale), known-groups validity, and responsiveness (correlations of change scores) were evaluated. Results Mean patient age ranged from 66.5 to 71.5 years and the majority of patients were female. Initial assessments in the vaccine trial (ARI Day 1) were suggestive of less severe illness than in the observational studies with hospitalized patients. CFA loadings (> 0.40) supported summary scores. ICCs exceeding the recommended threshold of 0.70 supported test–retest reliability for Respiratory and Systemic Symptoms, except in the small observational study. At the scale level, correlations were moderate to strong (|r| ≥ 0.3) and positive between the Respiratory Symptoms Scale and the related clinical questionnaire scores, reflecting measurement of similar symptoms in support of convergent validity. Correlations with change in Patient Global Impression of Severity > 0.30 supported responsiveness. Conclusions Psychometric tests applied to the RiiQ™ Symptoms scales provide evidence of its reliability, construct validity, discriminating ability, and responsiveness for use in clinical studies to assess the onset and severity of RSV symptoms.

Inflammatory breast cancer (IBC) poses an ongoing challenge as rates of disease recurrence and mortality remain high compared to stage-matched controls. However, frontline therapy has evolved through the years, including the widespread use of neoadjuvant chemotherapy (NAC) given the prognostic importance of pathologic complete response (pCR). Due to these sweeping changes, we need new data to assess current recurrence and survival outcomes for locally advanced IBC in the context of matched non-inflammatory controls. We conducted a retrospective analysis of institutional IBC data from 2010 to 2016 with the primary objective of comparing overall survival (OS), relapse-free survival (RFS), and distant relapse-free survival (DRFS). We matched IBC patients to non-inflammatory controls based on age, receptor status, tumor grade, clinical stage, and receipt of prior NAC. Secondary objectives included assessing pCR rates and identifying prognostic factors. Among NAC recipients, we observed similar pCR rates (47.6 % vs. 49.4 %, p = 0.88) between IBC (n = 84) and matched non-IBC (n = 81) cohorts. However, we noted a significant worsening of OS (p = 0.0001), RFS (p = 0.0001), and DRFS (p = 0.001) in the IBC group. Specifically, 5-year OS in the IBC cohort was 58.9 % vs. 86.7 % for matched controls (p = 0.0003). Older age was a weak negative predictor for OS (HR 1.03, p = 0.001) and RFS (HR 1.02, p = 0.01). For DRFS, older age was also a weak negative predictor (HR 1.02, p = 0.02), whereas the use of NAC was a positive predictor (HR 0.47, p = 0.02). Despite no clear difference in pCR, survival outcomes remain poor for IBC compared to matched non-inflammatory controls.

Abstract Background In the general population, sensory impairments increase markedly with age in adults over 60 years of age. We estimated the prevalence of hearing loss only (HL), vision loss only (VL), and a combined impairment (i.e., dual sensory loss or DSL) in Canadians receiving home care (HC) or long-term care (LTC). Methods Annual cross-sectional analyses were conducted using data collected with one of two interRAI assessments, one used for the HC setting (n = 2,667,199), and one for LTC (n = 1,538,691). Items in the assessments were used to measure three mutually exclusive outcomes: prevalence of VL only, HL only, or DSL. Trends over time for each outcome were examined using the Cochran-Armitage trend test. A negative binomial model was used to quantify the trends over time for each outcome while adjusting for age, sex and province. Results In HC, there was a significant trend in the rate for all three outcomes (p < 0.001), with a small increase (roughly 1%) each year. In HC, HL was the most prevalent sensory loss, with a rate of roughly 25% to 29%, while in LTC, DSL was the most prevalent impairment, at roughly 25% across multiple years of data. In both settings, roughly 60% of the sample was female. Males in both HC and LTC had a higher prevalence of HL compared to females, but the differences were very small (no more than 2% in any given year). The prevalence of HL differed by province after adjusting for year, age and sex. Compared to Ontario, Yukon Territory had a 26% higher rate of HL in HC (relative rate [RR] = 1.26; 95% confidence interval [CI]:1.11, 1.43), but LTC residents in Newfoundland and Labrador had a significantly lower rate of HL (RR: 0.57; CI: 0.43, 0.76).When combined, approximately 60% of LTC residents, or HC clients, had at least one sensory impairment. Conclusions Sensory impairments are highly prevalent in both HC and LTC, with small sex-related differences and some variation across Canadian provinces. The interRAI assessments provide clinicians with valuable information to inform care planning and can also be used to estimate the prevalence of these impairments in specific population sub-groups.

Abstract Background Prognostic accuracy is important throughout all stages of the illness trajectory as it has implications for the timing of important conversations and decisions around care. Physicians often tend to over-estimate prognosis and may under-recognize palliative care (PC) needs. It is therefore essential that all relevant stakeholders have as much information available to them as possible when estimating prognosis. Aims The current study examined whether the interRAI Changes in Health, End-Stage Disease, Signs and Symptoms (CHESS) Scale is a good predictor of mortality in a known PC population and to see how it compares to the Palliative Performance Scale (PPS) in predicting 90-day mortality. Methods This retrospective cohort study used data from 2011 to 2018 on 80,261 unique individuals receiving palliative home care and assessed with both the interRAI Palliative Care instrument and the PPS. Logistic regression models were used to evaluate the relationship between the main outcome, 90-day mortality and were then replicated for a secondary outcome examining the number of nursing visits. Comparison of survival time was examined using Kaplan-Meier survival curves. Results The CHESS Scale was an acceptable predictor of 90-day mortality (c-statistic = 0.68; p

Antibody–drug conjugates (ADCs) constitute a rapidly expanding category of biopharmaceuticals that are reshaping the landscape of targeted chemotherapy. The meticulous process of selecting therapeutic targets, aided by specific monoclonal antibodies’ high specificity for binding to designated antigenic epitopes, is pivotal in ADC research and development. Despite ADCs’ intrinsic ability to differentiate between healthy and cancerous cells, developmental challenges persist. In this study, we present a rationalized pipeline encompassing the initial phases of the ADC development, including target identification and validation. Leveraging an in-house, computationally constructed ADC target database, termed ADC Target Vault, we identified a set of novel ovarian cancer targets. We effectively demonstrate the efficacy of Surface Plasmon Resonance (SPR) technology and in vitro models as predictive tools, expediting the selection and validation of targets as ADC candidates for ovarian cancer therapy. Our analysis reveals three novel robust antibody/target pairs with strong binding and favourable antibody internalization rates in both wild-type and cisplatin-resistant ovarian cancer cell lines. This approach enhances ADC development and offers a comprehensive method for assessing target/antibody combinations and pre-payload conjugation biological activity. Additionally, the strategy establishes a robust platform for high-throughput screening of potential ovarian cancer ADC targets, an approach that is equally applicable to other cancer types.

Objective As part of a quality improvement project, we developed and employed an observation checklist to measure patient-centered behaviors during daily rounds to assess the frequency of patient-centered behaviors among a patient-centered care (PCC) team and standard team (ST) rounds. Patients and Methods On four general medicine service (GMS) teaching teams at an urban academic medical center in which housestaff rotate, we utilized an observation checklist to assess the occurrence of eight behaviors on inpatient daily rounds. The checklist covered domains of patient-centered communication, etiquette-based behaviors, and shared decision-making. One GMS team is guided by a PCC curriculum that emphasizes patient-centered communication strategies, but not specifically behaviors during bedside rounds. Results Between August 2018 and May 2019 a trained observer completed 448 observations of patient rounding encounters using the checklist. Across all teams, 46.0% of the 8 behaviors were performed when possible, with more done on the PCC team (58.0%) than ST (42.0%), p

Objective:Leptomeningeal carcinomatosis (LMC), a common complication of advanced malignancies, is associated with high morbidity and mortality, yet diagnosis and treatment decisions remain challenging. This study describes the diagnostic and treatment modalities for LMC and identifies factors associated with overall survival (OS).Materials and Methods:We performed a single-institution retrospective study (registration #: OSU2016C0053) of 153 patients diagnosed with LMC treated at The Ohio State University, Comprehensive Cancer Center, (OSUCCC)-James between January 1, 2010 and December 31, 2015.Results:Median age at diagnosis was 55.7 years, and 61% had Eastern Cooperative Oncology Group baseline performance status ≤1. Most common primary tumors were breast (43%), lung (26%), and cutaneous melanoma (10%). At presentation, most patients were stage III-IV (71%) with higher grade tumors (grade III: 46%). Metastases to bone (36%), brain (33%), and lung (12%) were the most common sites with a median of 0.5 years (range, 0-14.9 years) between the diagnosis of first metastasis and of LMC. 153 (100%) patients had MRI evidence of LMC. Of the 67 (44%) who underwent lumbar puncture (LP), 33 (22%) had positive cerebrospinal fluid (CSF) cytology. Most patients received radiotherapy for LMC (60%) and chemotherapy (93%) for either the primary disease or LMC. 28 patients received intrathecal chemotherapy, 22 of whom had a primary diagnosis of breast cancer. 98% died with median OS of all patients was 1.9 months (95% CI: 1.3-2.5 months).Conclusion:Despite improved treatments and targeted therapies, outcomes of LMC remain extremely poor. Positive CSF cytology was associated with lower OS in patients who had cytology assessed and specifically in patients with breast cancer. CSF cytology serves as an important indicator for prognosis and helps aid in developing individualized therapeutic strategies for patients with LMC.

Abstract Background Most individuals who typically receive palliative care (PC) tend to have cancer and a relatively short prognosis (

Abstract Background The stressful nature of medical training and other work-related factors put postgraduate medical trainees at high risk of burnout and poor psychological wellbeing. This has negative implications for patient care and the effectiveness of the healthcare system. The structure of the healthcare system and postgraduate medical education in Australia is different to that of other countries. Whilst a significant body of research exists on burnout and wellbeing in trainees in the USA, evidence specific to Australian trainees is lacking. The aim of this review is to synthesise the current knowledge on the factors that impact burnout and psychological wellbeing in Australian postgraduate medical trainees. Methods/design A systematic review will be conducted across eight digital databases: Academic Search Complete, MEDLINE, Embase, Web of Science, PsychInfo, Scopus, CINAHL Plus and Informit Health Collection. Peer reviewed empirical studies and relevant grey literature published after 2000 that address an aspect of burnout or psychological wellbeing in Australian postgraduate medical trainees will be included. Two reviewers will independently review each article against the inclusion and exclusion criteria, with disagreements resolved via discussion and consensus. Data will be extracted using a standard form and quality will be assessed using the assessment tools available from the Joanna Briggs Institute. A thematic narrative synthesis of the studies will be presented, along with an assessment of current gaps in the literature and areas for future research. Discussion This review will be the first to integrate the evidence on burnout and psychological wellbeing specific to Australian postgraduate medical trainees. The findings will contribute to a better understanding of the factors that impact burnout and psychological wellbeing in this population and will lay the foundation for future research into appropriate strategic interventions. Systematic review registration This protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42020203195 ).

Abstract Background Canadian palliative care (PC) philosophy seeks to support individuals in a person-centered and sensitive manner. Unfortunately, philosophy does not necessarily translate into practice and this divide may leave patients without appropriate care at the end of life, causing distress for some families. The primary goal of the study was to identify key factors affecting perceptions of quality PC from the perspective of informal caregivers and decision makers (e.g., program managers) and to understand how their experiences within the health care system may have influenced their perceptions. Methods Nine caregivers and 11 decision makers from Yukon Territory, British Columbia, Alberta, Ontario, & Nova Scotia shared their experiences in PC via interview or focus group. Audio recordings were transcribed verbatim and qualitatively analyzed for themes. Results Three themes emerged, including the Caregiver as Anchor, Bewildering System, and Patient, Caregiver, and Family-Centered Care. While these results resembled other studies on caregivers and individuals receiving PC, the present study also uncovered systemic concerns. There was agreement between the two participant groups across most subthemes, however only caregivers reported feelings of being trapped by the health care system and a general lack of respect from health care professionals. Additionally, caregivers stressed the importance of preserving some sort of normalcy in daily life despite the individual’s illness. Conclusions Caregivers are critical. The health care system expects them to help a great deal, but they often do not feel supported or respected and the system is lacking the capacity and resources to meet their needs while they are grieving loss and struggling to meet demands.

BackgroundOvarian cancer (OC) is amongst the most lethal of common cancers in women. Lacking in specific symptoms in the early stages, OC is predominantly diagnosed late when the disease has undergone metastatic spread and chemotherapy is relied on to prolong life. Platinum-based therapies are preferred and although many tumors respond initially, the emergence of platinum-resistance occurs in the majority of cases after which prognosis is very poor. Upregulation of DNA damage pathways is a common feature of platinum resistance in OC with cyclin dependent kinases (CDKs) serving as key regulators of this process and suggesting that CDK inhibitors (CDKis) could be effective tools in the treatment of platinum resistant and refractory OC.AimThe aim of this study was to evaluate the efficacy of CDKis in platinum resistant OC models and serve as a predictor of potential clinical utility.MethodsThe efficacy of CDKi, dinaciclib, was determined in wildtype and platinum resistant cell line pairs representing different OC subtypes. In addition, dinaciclib was evaluated in primary cells isolated from platinum-sensitive and platinum-refractory tumors to increase the clinical relevance of the study.Results and conclusionsDinaciclib proved highly efficacious in OC cell lines and primary cells, which were over a thousand-fold more sensitive to the CDKi than to cisplatin. Furthermore, cisplatin resistance in these cells did not influence sensitivity to dinaciclib and the two drugs combined additively in both platinum-sensitive and platinum-resistant OC cells suggesting a potential role for pan-CDKis (CDKis targeting multiple CDKs), such as dinaciclib, in the treatment of advanced and platinum-resistant OC.

Introduction Proximal humerus fractures (PHFs) comprise

Abstract Background Triple-negative breast cancer (TNBC) is a heterogeneous disease and we have previously shown that rapid relapse of TNBC is associated with distinct sociodemographic features. We hypothesized that rapid versus late relapse in TNBC is also defined by distinct clinical and genomic features of primary tumors. Methods Using three publicly-available datasets, we identified 453 patients diagnosed with primary TNBC with adequate follow-up to be characterized as ‘rapid relapse’ (rrTNBC; distant relapse or death ≤2 years of diagnosis), ‘late relapse’ (lrTNBC; > 2 years) or ‘no relapse’ (nrTNBC: > 5 years no relapse/death). We explored basic clinical and primary tumor multi-omic data, including whole transcriptome (n = 453), and whole genome copy number and mutation data for 171 cancer-related genes (n = 317). Association of rapid relapse with clinical and genomic features were assessed using Pearson chi-squared tests, t-tests, ANOVA, and Fisher exact tests. We evaluated logistic regression models of clinical features with subtype versus two models that integrated significant genomic features. Results Relative to nrTNBC, both rrTNBC and lrTNBC had significantly lower immune signatures and immune signatures were highly correlated to anti-tumor CD8 T-cell, M1 macrophage, and gamma-delta T-cell CIBERSORT inferred immune subsets. Intriguingly, lrTNBCs were enriched for luminal signatures. There was no difference in tumor mutation burden or percent genome altered across groups. Logistic regression mModels that incorporate genomic features significantly outperformed standard clinical/subtype models in training (n = 63 patients), testing (n = 63) and independent validation (n = 34) cohorts, although performance of all models were overall modest. Conclusions We identify clinical and genomic features associated with rapid relapse TNBC for further study of this aggressive TNBC subset.

The naphthalene diimide compound QN-302, designed to bind to G-quadruplex DNA sequences within the promoter regions of cancer-related genes, has high anti-proliferative activity in pancreatic cancer cell lines and anti-tumor activity in several experimental models for the disease. We show here that QN-302 also causes downregulation of the expression of the S100P gene and the S100P protein in cells and in vivo. This protein is well established as being involved in key proliferation and motility pathways in several human cancers and has been identified as a potential biomarker in pancreatic cancer. The S100P gene contains 60 putative quadruplex-forming sequences, one of which is in the promoter region, 48 nucleotides upstream from the transcription start site. We report biophysical and molecular modeling studies showing that this sequence forms a highly stable G-quadruplex in vitro, which is further stabilized by QN-302. We also report transcriptome analyses showing that S100P expression is highly upregulated in tissues from human pancreatic cancer tumors, compared to normal pancreas material. The extent of upregulation is dependent on the degree of differentiation of tumor cells, with the most poorly differentiated, from more advanced disease, having the highest level of S100P expression. The experimental drug QN-302 is currently in pre-IND development (as of Q1 2023), and its ability to downregulate S100P protein expression supports a role for this protein as a marker of therapeutic response in pancreatic cancer. These results are also consistent with the hypothesis that the S100P promoter G-quadruplex is a potential therapeutic target in pancreatic cancer at the transcriptional level for QN-302.

BackgroundSpinal cord injury (SCI) in infancy halts typical development secondary to paralysis/paresis and the limited ability to engage with the environment. Traditional therapies further restrict a child via bracing, equipment, and medications. In contrast, activity-based restorative therapies (ABRT) promote activation of the neuromuscular system below the level of injury and affords a more typical sensorimotor experience.Case DescriptionA premature male infant exhibiting hypotonia, poor head control, and extremity weakness was diagnosed at age 5 months with a remote incomplete upper cervical SCI based on magnetic resonance imaging (MRI), presumed to have occurred perinatally. From 4 to 15 months of age, he received physical, occupational and speech therapies. Enrolled in an ABRT program at 15 months, he was unable to sit, pull-to-stand, stand, or walk and had upper extremity impairments. Results of the Bayley-III Scales of Infant and Toddler Development revealed gross and fine motor scores consistent with a 4-month-old.MethodsActivity-based restorative therapies was provided 5 day/week: 1.5 h of activity-based locomotor training and 1 h of activity-based occupational therapy.ResultsActivity-based restorative therapies are reported for 177 sessions and are on-going. Improvements are noted in trunk control, standing, walking, grasp, in-hand manipulation, and associated kinematics. Bayley-III fine motor score improved to that of a 16-month-old and gross motor score to that of a 7-month-old.DiscussionWhile the two treatment periods (i.e., 4–15 months old and 15–24 months) were each ∼9 months, the child’s accelerated progress toward typical development during the latter, ABRT period is noteworthy. In comparison to the period of traditional therapies in which paralysis was compounded by a restrictive environment and compensation, ABRT provided a potentially rich sensorimotor experience with an emphasis on active weight-bearing and proper kinematics to activate the neuromuscular system below the lesion in an age-appropriate, task-specific context of activities. Improved physical capacity enabled exploration more typically associated with development at this age expanding the positive impact to other developmental domains.

Abstract Background Trastuzumab-induced cardiotoxicity (TIC) can lead to early discontinuation of adjuvant therapy, however there is limited evidence on long-term survival outcomes in patients with operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) experiencing treatment interruption or discontinuation. Methods The primary objective of the study was to evaluate disease-free survival (DFS) in non-metastatic, HER2-positive, female BC patients who experienced treatment interruption or early discontinuation of trastuzumab therapy. Clinical and histopathological data were collected on 400 patients at The Ohio State University, an NCI-designated comprehensive cancer center between January 2005 and December 2015. Treatment interruption was defined as any delay of ≥2 weeks during trastuzumab therapy, including permanent cessation prior to completing planned therapy. TIC was defined as LVEF 15 points decline from baseline as evaluated by 2D echocardiogram after initiation of (neo) adjuvant therapy. DFS was defined as the time from diagnosis to first recurrence (loco-regional or distant recurrence) including second primary BC or death. Overall survival (OS) was defined as the time from diagnosis to death or last known follow up. OS/DFS estimates were generated using Kaplan-Meier methods and compared using Log-rank tests. Cox proportional hazard models were used to calculate adjusted hazard ratios (aHR) for OS/DFS. Results A total of 369 patients received trastuzumab therapy; 106 (29%) patients experienced treatment interruption at least once and 42 (11%) permanently discontinued trastuzumab prior to completing planned therapy. TIC was the most common reason for interruption (66 patients, 62%). The median duration of trastuzumab in patients with treatment interruption was 11.3 months (range: 0.5–16.9) with 24 (23%) patients receiving ≤6 months of therapy. This duration includes the time delay related to treatment interruption. Patients with any treatment interruption had worse DFS (aHR: 4.4, p = 0.001) and OS (aHR: 4.8, p

Objective: The primary objective of this study was to delineate differences in management, overall and distant disease-free survival in males diagnosed with breast cancer and treated at The Ohio State University Comprehensive Cancer Center as compared to comprehensively matched female subjects. Secondary objectives included assessment of clinical and histopathologic features and recurrence score, as measured by Oncotype DX and the modified Magee equation #2.Materials and Methods: This single institution retrospective study compared male and comprehensively matched female patients (1:2) with stage I-III breast cancer between 1994 and 2014. Recurrence risk was estimated using a modified Magee equation. Overall survival and distant disease-free survival were estimated and compared using Kaplan-Meier and Log-rank methods.Results: Forty-five male breast cancer patients were included (stage I: 26.7%; stage II: 53.3%; stage III: 20.0%; hormone receptor positive: 97.8%; human epidermal growth factor receptor 2 negative: 84.4%) with a median age of 63.8 (43.0-79.4) years at diagnosis. Intermediate and low recurrence scores were most common in male and female patients respectively; mean score was similar between groups (20.3 vs. 19.8). The proportion of male breast cancer patients treated with adjuvant chemotherapy and post-mastectomy radiation was lower compared to female patients (42.2% vs. 65.3%, p=0.013; 22.7% vs. 44.4%, p=0.030, respectively). Overall survival and distant disease-free survival between male and female patients were similar.Conclusion: Male breast cancer patient outcomes were similar compared to well-matched female patients suggesting that breast cancer specific factors are more prognostic than gender.

Abstract Background Evidence-based practice in geriatric oncology is growing, and national initiatives have focused on expanding cancer care and research to improve health outcomes for older adults. However, there are still gaps between knowledge and practice for older adults with cancer. Main text Here we provide a detailed methodology of geriatric oncology care delivery within a single institution. The Cancer and Aging Resiliency (CARE) clinic is a multidisciplinary approach for implementing geriatric-driven health care for older adults with cancer. The CARE clinic was developed as a direct response to recommendations targeting key multifactorial geriatric health conditions (e.g. falls, nutritional deficits, sensory loss, cognitive impairment, frailty, multiple chronic conditions, and functional status). The multidisciplinary team assesses and delivers a comprehensive set of recommendations, all in one clinic visit, to minimize burden on the patient and the caregiver. The CARE clinic consultative model is a novel approach integrating cancer subspecialties with geriatric oncology healthcare delivery. Conclusions Older adults with cancer have unique needs that are independent of routine oncology care. The CARE clinic model provides specific assessments and interventions to improve health outcomes among older adults with cancer.

Abstract Background While combinations of immune checkpoint (ICP) inhibitors and neo-adjuvant chemotherapy (NAC) have begun testing in patients with breast cancer (BC), the effects of chemotherapy on ICP expression in circulating T cells and within the tumor microenvironment are still unclear. This information could help with the design of future clinical trials by permitting the selection of the most appropriate ICP inhibitors for incorporation into NAC. Methods Peripheral blood samples and/or tumor specimens before and after NAC were obtained from 24 women with operable BC. The expression of CTLA4, PD-1, Lag3, OX40, and Tim3 on circulating T lymphocytes before and at the end of NAC were measured using flow cytometry. Furthermore, using multi-color immunohistochemistry (IHC), the expression of immune checkpoint molecules by stromal tumor-infiltrating lymphocytes (TILs), CD8+ T cells, and tumor cells was determined before and after NAC. Differences in the percentage of CD4+ and CD8+ T cells expressing various checkpoint receptors were determined by a paired Student’s t-test. Results This analysis showed decreased ICP expression by circulating CD4+ T cells after NAC, including significant decreases in CTLA4, Lag3, OX40, and PD-1 (all p values

Abstract Background To assess metastatic breast cancer (MBC) patient psychological factors, perceptions, and comprehension of tumor genomic testing. Methods In a prospective, single institution, single-arm trial, patients with MBC underwent next-generation sequencing at study entry with sequencing results released at progression. Patients who completed surveys before undergoing sequencing were included in the present secondary analysis (n = 58). We administered four validated psychosocial measures: Center for Epidemiologic Studies Depression Scale, Beck Anxiety Inventory, Trust in Physician Scale, and Communication and Attitudinal Self-Efficacy scale for Cancer. Genetic comprehension was assessed using 7-question objective and 6-question subjective measures. Longitudinal data were assessed (n = 40) using paired Wilcoxon signed rank and McNemar’s test of agreement. Results There were no significant differences between the beginning and end of study in depression, anxiety, physician trust, or self-efficacy (median time on study: 7.6 months). Depression and anxiety were positively associated with each other and both negatively associated with self-efficacy. Self-efficacy decreased from pre- to post-genomic testing (p = 0.05). Objective genetics comprehension did not significantly change from pre- to post-genomic testing, but patients expressed increased confidence in their ability to teach others about genetics (p = 0.04). Objective comprehension was significantly lower in non-white patients (p = 0.02) and patients with lower income (p = 0.04). Conclusions This is the only study, to our knowledge, to longitudinally evaluate multiple psychological metrics in MBC as patients undergo tumor genomic testing. Overall, psychological dimensions remained stable over the duration of tumor genomic testing. Among patients with MBC, depression and anxiety metrics were negatively correlated with patient self-efficacy. Patients undergoing somatic genomic testing had limited genomic knowledge, which varied by demographic groups and may warrant additional educational intervention. Clinical trial information NCT01987726 , registered November 13, 2013.

Abstract Background The purpose of this study is to highlight the experiences of women who are often hidden in what we know and understand about homelessness, and to make policy and practice recommendations for women-centred services including adaptations to current housing interventions. Methods Three hundred survey interviews were conducted with people experiencing homelessness in Calgary, Alberta, Canada. The survey instrument measured socio-demographics, adverse childhood experiences, mental and physical health, and perceived accessibility to resources. Eighty-one women participants were identified as a subsample to be examined in greater depth. Descriptive statistics and logistic regressions were calculated to provide insight into women respondents’ characteristics and experiences of homelessness and how they differed from men’s experiences. Results Women’s experiences of homelessness are different from their male counterparts. Women have greater mental health concerns, higher rates of diagnosed mental health issues, suicidal thoughts and attempts, and adverse childhood trauma. The results should not be considered in isolation, as the literature suggests, because they are highly interconnected. Conclusion In order to ensure that women who are less visible in their experiences of homelessness are able to access appropriate services, it is important that service provision is both gender specific and trauma-informed. Current Housing First interventions should be adapted to ensure women’s safety is protected and their unique needs are addressed.

Abstract Background Metaplastic breast cancer remains poorly characterized given its rarity and heterogeneity. The majority of metaplastic breast cancers demonstrate a phenotype of triple-negative breast cancer; however, differences in clinical outcomes between metaplastic breast cancer and triple-negative breast cancer in the era of third-generation chemotherapy remain unclear. Methods We compared the clinical outcomes between women with metaplastic breast cancer and women with triple-negative breast cancer diagnosed between 1994 and 2014. Metaplastic breast cancer patients were matched 1:3 to triple-negative breast cancer patients by stage and age at diagnosis. Distant disease-free survival (DDFS) and overall survival (OS) were estimated using Kaplan Meier methods and Cox proportional hazard regression models. Immune checkpoint markers were characterized by immunohistochemistry in a subset of samples. Results Forty-four metaplastic breast cancer patients (stage I 14%; stage II 73%; stage III 11%; stage IV 2%) with an average age of 55.4 (± 13.9) years at diagnosis. Median follow-up for the included metaplastic breast cancer and triple-negative breast cancer patients (n = 174) was 2.8 (0.1–19.0) years. The DDFS and OS between matched metaplastic breast cancer and triple-negative breast cancer patients were similar, even when adjusting for clinical covariates (DDFS: HR = 1.64, p = 0.22; OS: HR = 1.64, p = 0.26). Metaplastic breast cancer samples (n = 27) demonstrated greater amount of CD163 in the stroma (p = 0.05) and PD-L1 in the tumor (p = 0.01) than triple-negative breast cancer samples (n = 119), although more triple-negative breast cancer samples were positive for CD8 in the tumor than metaplastic breast cancer samples (p = 0.02). Conclusions Patients with metaplastic breast cancer had similar outcomes to those with triple-negative breast cancer based on DDFS and OS. The immune checkpoint marker profile of metaplastic breast cancers in this study may prove useful in future studies attempting to demonstrate an association between immune profile and survival.

BackgroundIndividuals receiving palliative care (PC) are generally thought to prefer to receive care and die in their homes, yet little research has assessed the quality of home- and community-based PC. This project developed a set of valid and reliable quality indicators (QIs) that can be generated using data that are already gathered with interRAI assessments-an internationally validated set of tools commonly used in North America for home care clients. The QIs can serve as decision-support measures to assist providers and decision makers in delivering optimal care to individuals and their families.MethodsThe development efforts took part in multiple stages, between 2017-2021, including a workshop with clinicians and decision-makers working in PC, qualitative interviews with individuals receiving PC, families and decision makers and a modified Delphi panel, based on the RAND/ULCA appropriateness method.ResultsBased on the workshop results, and qualitative interviews, a set of 27 candidate QIs were defined. They capture issues such as caregiver burden, pain, breathlessness, falls, constipation, nausea/vomiting and loneliness. These QIs were further evaluated by clinicians/decision makers working in PC, through the modified Delphi panel, and five were removed from further consideration, resulting in 22 QIs.ConclusionsThrough in-depth and multiple-stakeholder consultations we developed a set of QIs generated with data already collected with interRAI assessments. These indicators provide a feasible basis for quality benchmarking and improvement systems for care providers aiming to optimize PC to individuals and their families.

Brain metastases are a devastating sequela of common primary cancers (e.g., lung, breast, and skin) and have limited effective therapeutic options. Previously, systemic chemotherapy failed to demonstrate significant benefit in patients with brain metastases, but in recent decades, targeted therapies and more recently immune checkpoint inhibitors (ICIs) have yielded promising results in preclinical and clinical studies. Furthermore, there is significant interest in harnessing the immunomodulatory effects of radiotherapy (RT) to synergize with ICIs. Herein, we discuss studies evaluating the impact of RT dose and fractionation on the immune response, early studies supporting the synergistic interaction between RT and ICIs, and ongoing clinical trials assessing the benefit of combination therapy in patients with brain metastases.

Purpose: Tumor lysis syndrome (TLS) is a rare but life-threatening phenomenon that occurs mainly in patients with aggressive hematologic or highly chemotherapy sensitive solid tumors such as high-grade neuroendocrine carcinoma or testicular cancer. Tumor lysis syndrome is exceedingly rare in hormone receptor-positive, HER2-negative breast cancer. Furthermore, TLS following treatment with alpelisib, a novel phosphatidylinositol 3-kinase (PI3K) inhibitor used to treat PIK3CA -mutated (gene encoding p110α subunit of PI3K), hormone receptor positive advanced breast cancer, has never been described in patients with nonhematologic malignancies. Methods: In the following case, we present a patient with hormone receptor-positive, HER2-negative, PIK3CA -mutated metastatic breast cancer who developed TLS 12 days after starting fulvestrant and alpelisib. Results: Patient was promptly treated with improvement in her renal function to baseline without requiring renal replacement therapy. Alpelisib was resumed at a reduced dose with no further complications. Conclusion: Through this case, we discuss the potential complications of TLS and the importance of prompt recognition and treatment.

To discover DNA ligands against a predetermined receptor protein complex, we introduce a comprehensive version of ligand-guided selection (LIGS). LIGS is, itself, a variant of systematic evolution of ligands by exponential enrichment (SELEX). Herein, we have optimized LIGS to identify higher affinity aptamers with high specificity. In addition, we demonstrate the expandability of LIGS by performing specific aptamer elution at 25°C, utilizing multiple monoclonal antibodies (mAbs) against cultured cells and primary cells obtained from human donors expressing the same receptor. Eluted LIGS libraries obtained through Illumina high-throughput (HT) DNA sequencing were analyzed by bioinformatics tools to discover five DNA aptamers with apparent affinities ranging from 3.06 ± 0.485 nM to 325 ± 62.7 nM against the target, T cell receptor-cluster of differentiation epsilon (TCR-CD3ε) expressed on human T cells. The specificity of the aptamers was validated utilizing multiple strategies, including competitive binding analysis and a double-knockout Jurkat cell line generated by CRISPR technology. The cross-competition experiments using labeled and unlabeled aptamers revealed that all five aptamers compete for the same binding site. Collectively, the data in this report introduce a modified LIGS strategy as a universal platform to identify highly specific multiple aptamers toward multi-component receptor proteins in their native state without changing the cell-surface landscape. Keywords: Aptamers, SELEX, ligands, LIGS, CD3epsilon, T cells, nucleic acids

Estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) belong to a superfamily of nuclear receptors called steroid hormone receptors, which, upon binding ligand, dimerize and translocate to the nucleus where they activate or repress the transcription of a large number of genes, thus modulating critical physiologic processes. ERβ has multiple isoforms that show differing association with prognosis. Expression levels of the full length ERβ1 isoform are often lower in aggressive cancers as compared to normal tissue. High ERβ1 expression is associated with improved overall survival in women with breast cancer. The promise of ERβ activation, as a potential targeted therapy, is based on concurrent activation of multiple tumor suppressor pathways with few side effects compared to chemotherapy. Thus, ERβ is a nuclear receptor with broad-spectrum tumor suppressor activity, which could serve as a potential treatment target in a variety of human cancers including breast cancer. Further development of highly selective agonists that lack ERα agonist activity, will be necessary to fully harness the potential of ERβ.

Primary small cell carcinoma of the breast (SCCB) is a rare tumor subtype comprising

Abstract Background Pain is one of the most important domains affecting health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). Secukinumab has demonstrated rapid and sustained improvements in signs and symptoms, including HRQoL, among patients with active PsA. This analysis evaluates the effect of secukinumab on patient-reported pain in PsA through 104 weeks of treatment. Methods Pain was assessed through week 104 using clinically relevant measures, including change from baseline in a pain visual analog scale (VAS) and Short Form-36 (SF-36) bodily domain scores; proportion of patients reporting improvements equal to or better than minimum clinically meaningful differences in the pain VAS and SF-36 bodily pain domain scores; and proportion of patients with no, moderate, or extreme pain/discomfort measured by the EuroQoL 5-Dimension 3-Level Questionnaire (EQ-5D-3 L) pain item scores. Correlations of pain measures were analyzed using Pearson’s correlation coefficient. Pre-specified analyses of TNF-naïve patients and patients who stopped TNF-inhibitors (TNFis) due to inadequate responses or safety/tolerability (TNF-IR patients) were performed using “as-observed data.” Results Mean improvements from baseline in pain VAS scores were greater with secukinumab versus placebo by week 3 (− 16.9; P

The seeds of chronic homelessness, with the addictions and mental illness that often accompany it, are sown frequently in traumatic childhoods. A survey of 300 people experiencing chronic homelessness and those sleeping rough in Calgary reveals that these individuals have suffered childhood trauma at a rate five times higher than the general population. Those traumas include neglect, parents with addiction issues, domestic violence and abuse. Unfortunately for those seeking help, community-based services in Calgary have been unable to keep up since the prevailing philosophy became one of releasing these people from institutions into the community. A 62 per cent reduction in psychiatric beds some 30 years ago was accompanied by levels of funding that simply weren’t enough to provide all the resulting community services needed. People without families to turn to, and with no social supports, tended to end up homeless. It has become a vicious circle – while mental health issues can lead to homelessness, homelessness also puts people at greater risk for mental illness. Because childhood trauma plays such a key role in chronic homelessness, it needs to be figured into the kinds of housing and support programs that are put in place for people who are homeless. Psychiatric supports should be among the programs that homeless shelters offer and should also be provided on a priority basis for people using the intervention program called Housing First. There is no doubt about the link between adverse childhood experiences and future mental health problems. People who have experienced at least four types of childhood trauma are 12 times more likely to have attempted suicide, seven times more likely to be alcoholic, and 10 times more likely to have injected street drugs. They are also much more likely to be violent. Interaction with the health-care and justice systems started early for the individuals surveyed in Calgary, aged between 18 and 80. Forty-two per cent of them had been foster children. Within the past year, 59 per cent had slept rough, 31 per cent had spent time in detox, 23 per cent had served jail time and 31 per cent had been in hospital. Eighty-two per cent regularly used alcohol, with 32 per cent using it daily and 70 per cent using drugs other than alcohol. Yet, the help that is available for the chronically homeless population is at best scattershot. More than 50 per cent of those surveyed who had received help for mental health and addiction issues said they didn’t get enough assistance. A quarter of those who didn’t receive treatment said they’d asked for help and hadn’t received it, while a third said long waitlists prevented them from accessing help. Many were in and out of a patchwork of programs with little to show for it. Solutions are not out of reach. Funding should target housing and case management programs designed to address the psychiatric issues resulting from childhood trauma. And Calgary’s network of community-based health care, housing and support programs should be expanded to help people suffering from multiple disorders. Currently, homeless shelters are serving as ad hoc institutions of mental health care for far too many people. With adequate funding and supports, long-term shelter users can be prioritized for psychiatric care, and shelters can return to their original mandate of being places where people who are temporarily homeless and in transition can get the help they need.

Abstract Background There are no clinical outcome assessment (COA) tools developed in accordance with Food and Drug Administration (FDA) guidance suitable for the evaluation of symptoms associated with respiratory syncytial virus (RSV) infection among infants. The Gilead RSV Caregiver Diary (GRCD) is being developed to fulfill this need; the present research evaluates the GRCD and documents its reliability, validity, and responsiveness among children

There is inconsistent evidence demonstrating a relationship between task complexity and hand preference. However, analyzing the point at which task complexity overrides the decision to demonstrate a biomechanically efficient movement can enable complexity to be quantified. Young children (ages 3–7), adolescents (ages 8–12), young adults (ages 18–25), and older adults (ages 65+) performed a newly developed Hand Selection Complexity Task (HSCT) and completed the Waterloo Handedness Questionnaire (WHQ). The HSCT included a reciprocal Fitts’ tapping task performed in the contralateral space (i.e., same side as preferred hand), followed by ipsilateral space (i.e., opposite side of preferred hand). An alternating contralateral-ipsilateral pattern enabled the participant to progress through six levels of difficulty in three conditions (manipulating target amplitude, width, and combined factors). As participants were free to perform with whichever hand (i.e., preferred, non-preferred) they deemed most appropriate, the level of difficulty where a hand switch occurred was identified. HSCT completion time and error scores were also computed. Findings revealed age to be a significant predictor of dependent measures when considering significant effects and interactions. Combined with the covariate WHQ score as a significant predictor of HSCT time and errors (in some, but not all cases), it can be argued that age-related effects reflect the development of handedness, and changes in strength of handedness across the lifespan. Together, findings suggest that task complexity plays an important role in hand selection when performing a task of increasing difficulty. It appears that task complexity will take precedent over object proximity and biomechanical efficiency, at a certain point, in order to complete the movement with the preferred hand. This point ultimately changes throughout the lifespan.

The objective of the current study was to understand the added effects of having a sensory impairment (vision and/or hearing impairment) in combination with cognitive impairment with respect to health-related outcomes among older adults (65+ years old) receiving home care or residing in a long-term care (LTC) facility in Ontario, Canada.Cross-sectional analyses were conducted using existing data collected with one of two interRAI assessments, one for home care (n = 291,824) and one for LTC (n = 110,578). Items in the assessments were used to identify clients with single sensory impairments (e.g., vision only [VI], hearing only [HI]), dual sensory impairment (DSI; i.e., vision and hearing) and those with cognitive impairment (CI). We defined seven mutually exclusive groups based on the presence of single or combined impairments.The rate of people having all three impairments (i.e., CI+DSI) was 21.3% in home care and 29.2% in LTC. Across the seven groups, individuals with all three impairments were the most likely to report loneliness, to have a reduction in social engagement, and to experience reduced independence in their activities of daily living (ADLs) and instrumental ADLs (IADLs). Communication challenges were highly prevalent in this group, at 38.0% in home care and 49.2% in LTC. In both care settings, communication difficulties were more common in the CI+DSI group versus the CI-alone group.The presence of combined sensory and cognitive impairments is high among older adults in these two care settings and having all three impairments is associated with higher rates of negative outcomes than the rates for those having CI alone. There is a rising imperative for all health care professionals to recognize the potential presence of hearing, vision and cognitive impairments in those for whom they provide care, to ensure that basic screening occurs and to use those results to inform care plans.

The incidence of thyroid cancer has risen dramatically in the past few decades. The cause of this is unclear, but several lines of evidence indicate it is largely due to overdiagnosis, the diagnosis of tumors that would have never manifest clinically if untreated. Practices leading to overdiagnosis may relate to defensive medicine. In this study, we evaluated the association between malpractice climate and incidence of thyroid, breast, prostate, colon, and lung cancer in U.S. states from 1999-2012 using publicly available government data. State-level malpractice risk was quantified as malpractice payout rate, the number of malpractice payouts per 100,000 people per state per year. Associations between state-level cancer incidence, malpractice payout rate, and several cancer risk factors were evaluated. Risk factors included several social determinants of health, including factors predicting healthcare access. States with higher malpractice payout rate had higher thyroid cancer incidence, on both univariate analysis (r = 0.51, P = 0.009, Spearman) and multivariate analysis (P

The comprehensive geriatric assessment (CGA) is a versatile tool for the care of the older person diagnosed with cancer. The purpose of this article is to detail how a CGA can be tailored to Ambulatory Geriatric Oncology Programs (AGOPs) in academic cancer centers and to community oncology practices with varying levels of resources. The Society for International Oncology in Geriatrics (SIOG) recommends CGA as a foundation for treatment planning and decision-making for the older person receiving care for a malignancy. A CGA is often administered by a multidisciplinary team (MDT) composed of professionals who provide geriatric-focused cancer care. CGA can be used as a one-time consult for surgery, chemotherapy, or radiation therapy providers to predict treatment tolerance or as an ongoing part of patient care to manage malignant and non-malignant issues. Administrative support and proactive infrastructure planning to address scheduling, referrals, and provider communication are critical to the effectiveness of the CGA.