Risk Factors for Early Treatment Discontinuation Due to Toxicity Among Patients With Metastatic Castration-resistant Prostate Cancer Receiving Androgen Receptor-targeted Therapy.

BACKGROUND: Androgen receptor-targeted therapies (ARTs) improve survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC); however, a significant portion of patients discontinue treatment for various reasons including treatment-related toxicity. We aim to describe reasons for ART treatment discontinuation and identify predictors associated with increased risk of treatment discontinuation due to toxicity. METHODS: We performed a single-institution retrospective review of patients with mCRPC receiving ART between 2010 and 2021. Our primary aim was to identify risk factors for treatment discontinuation due to toxicity. Our secondary aim was to describe ART discontinuation patterns among patients with mCRPC. RESULTS: One hundred thirty-three patients with mCRPC started and discontinued ARTs. Fourteen patients (10.5%) discontinued treatment due to toxicity. Common reasons for treatment discontinuation include Prostate Specific Antigen test progression, radiographic progression, toxicity, and death. Significant predictors of treatment discontinuation due to toxicity on bivariate analysis and multivariate analysis included patient-reported falls (odds ratio [OR]: 7.67, CI: [1.31-40.42]; P=0.016), rash (OR: 13.4, CI: [1.35-134.81]; P=0.026), and weakness (OR: 4.16, CI: [1.15-15.0]; P=0.019). CONCLUSIONS: Our work presents the first description of ART treatment discontinuation and its causes in the real-world setting, as well as patient-reported side effects. Most patients with mCRPC discontinued treatment due to the progression of disease and a minority of patients discontinued secondary to treatment toxicity. Initial multivariable analysis suggests that patient-reported weakness, falls, and rash were associated with a higher likelihood of treatment discontinuation due to toxicity. Early monitoring of this population can prolong the duration of treatment and prevent unnecessary treatment burden.

Telehealth follow-up consultations for melanoma patients during the COVID-19 pandemic: Patient and clinician satisfaction.

INTRODUCTION: The COVID-19 pandemic caused rapid implementation of telehealth for melanoma follow-up care in Australia. This study explores Australian melanoma patients and clinicians' level of satisfaction with telehealth. METHODS: A cross-sectional study was conducted across three specialist melanoma centres in Sydney, Australia. Melanoma patients (all stages) and clinicians completed mixed methods surveys seeking socio-demographic and clinical information and questionnaires to assess satisfaction with telehealth. Additionally, patients completed measures of quality of life, fear of cancer recurrence and trust in their oncologist. Patients and clinicians provided open-ended responses to qualitative questions about their perceptions of telehealth. RESULTS: One hundred and fifteen patients and 13 clinicians responded to surveys. Telephone was used by 109 (95%) patients and 11 (85%) clinicians. Fifty-seven (50%) patients and nine (69%) clinicians preferred face-to-face consultations, 38 (33%) patients and 3 (23%) clinicians preferred a combination of face-to-face and telehealth consultations. Five (4%) patients and nil clinicians preferred telehealth consultations. Patients diagnosed with early-stage melanoma, using telehealth for the first time, who have lower trust in their oncologist, and having higher care delivery, communication and supportive care concerns were likely to report lower satisfaction with telehealth. Open-ended responses were consistent between patients and clinicians, who reported safety, convenience and improved access to care as major benefits, while identifying personal, interpersonal, clinical and system-related disadvantages. DISCUSSION: While telehealth has been widely implemented during COVID-19, the benefits identified by patients and clinicians may extend past the pandemic. Telehealth may be considered for use in conjunction with face-to-face consultations to provide melanoma follow-up care.

Impact of cystic fibrosis multidisciplinary virtual clinics on patient experience, time commitments and costs.

BACKGROUND AND AIMS: The experience of outpatient care may differ for select patient groups. This prospective study evaluates the adult patient experience of multidisciplinary outpatient cystic fibrosis (CF) care with videoconferencing through telehealth compared with face-to-face care the year prior. METHODS: People with CF without a lung transplant were recruited. Patient-reported outcomes were obtained at commencement and 12 months into the study, reflecting both their face-to-face and telehealth through videoconferencing experience, respectively. Three patient cohorts were analysed: (i) participants with a regional residence, (ii) participants with a nonregional including metropolitan residence and (iii) participants with colonised multiresistant microbiota. RESULTS: Seventy-four patients were enrolled in the study (mean age, 37 ± 11 years; 50% male; mean forced expiratory volume in the first second of expiration, 60% [standard deviation, 23]) between February 2020 and May 2021. No differences between models were observed in the participants' rating of the health care team, general and mental health rating, and their confidence in handling treatment plans at home. No between-group differences in the Cystic Fibrosis Questionnaire - Revised (CFQ-R) were observed. Travel duration and the cost of attending a clinic was significantly reduced, particularly for the regional group (4 h, AU$108 per clinic; P < 0.05). A total of 93% respondents preferred to continue with a hybrid approach. CONCLUSION: In this pilot study, participants' experience of care and quality of life were no different with face-to-face and virtual care between the groups. Time and cost-savings, particularly for patients living in regional areas, were observed. Most participants preferred to continue with a hybrid model for outpatient care.

Antemortem tooth loss as a biomarker of poverty: Dental evidence of "weathering" in a contemporary U.S. skeletal sample.

In societies where resources are unequally distributed, structural inequities can be physically embodied over lifetimes. Lived experiences including racism, sexism, classism, and poverty can lead to chronic stress that prematurely ages body systems. This study tests the hypothesis that members of structurally vulnerable groups will exhibit premature aging in the form of antemortem tooth loss (AMTL). Analyzing Black, Indigenous, and People of Color (BIPOC) and white skeletal donors from the University of Tennessee, we predict that individuals from structurally vulnerable groups will exhibit more AMTL than individuals with more social privilege. We find some evidence for increased AMTL in BIPOC individuals, but significantly more AMTL in low-socioeconomic-status white individuals than either BIPOC or high-SES white individuals. We maintain that high rates of AMTL provide evidence of embodied consequences of social policies and utilize the violence continuum to theorize the ways in which poverty and inequity are normalized in U.S. society.

Limits to the strain engineering of layered square-planar nickelate thin films.

The layered square-planar nickelates, Ndn+1NinO2n+2, are an appealing system to tune the electronic properties of square-planar nickelates via dimensionality; indeed, superconductivity was recently observed in Nd6Ni5O12 thin films. Here, we investigate the role of epitaxial strain in the competing requirements for the synthesis of the n = 3 Ruddlesden-Popper compound, Nd4Ni3O10, and subsequent reduction to the square-planar phase, Nd4Ni3O8. We synthesize our highest quality Nd4Ni3O10 films under compressive strain on LaAlO3 (001), while Nd4Ni3O10 on NdGaO3 (110) exhibits tensile strain-induced rock salt faults but retains bulk-like transport properties. A high density of extended defects forms in Nd4Ni3O10 on SrTiO3 (001). Films reduced on LaAlO3 become insulating and form compressive strain-induced c-axis canting defects, while Nd4Ni3O8 films on NdGaO3 are metallic. This work provides a pathway to the synthesis of Ndn+1NinO2n+2 thin films and sets limits on the ability to strain engineer these compounds via epitaxy.

Perspectives of postdoctoral fellows: A qualitative study of clinical supervision in psycho-oncology.

Given the prevalence and distress associated with a cancer diagnosis, the training of psycho-oncology providers to meet the mental health needs of cancer survivors warrants investigation. Clinical supervision is a key teaching strategy for psychology trainees, particularly during a postdoctoral fellowship when trainees are gaining specialized training and making important career decisions. This qualitative study examined how postdoctoral fellows in psycho-oncology used clinical supervision and the supervisory relationship for their personal and professional development. Interviews were conducted with 10 postdoctoral trainees in the United States; data were analyzed using consensual qualitative research methodology. Five themes emerged from the data: supervisees' learning experiences in supervision, foundations and features of support derived from supervision, ethical and social issues, unmet needs in current supervision, and strategies to enhance future supervision. Supervision was a space to learn about leadership and supervisory skills, professional identity, career preferences, multidisciplinary teamwork, knowledge about cancer, emotional responses, self-care practices, ethical dilemmas, social and cultural issues, and power dynamics. Participants also shared needs that were not met in supervision, which included both missed content (e.g., professional development issues and clinical concerns) and constraints of the supervisory relationship. Drawing on the study findings, recommendations are made to enhance the supervisory relationship for both trainees and supervisors in psycho-oncology and to ensure clinicians can thrive while competently and compassionately working with cancer survivors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Does physical activity mediate the associations between blue space and mental health? A cross-sectional study in Australia.

BACKGROUND: Research has begun to examine whether blue space is beneficial to mental health. While results are promising, it is difficult to know which aspects of mental health or mental ill-health may benefit most. Physical activity has been proposed as one potential mechanism via which blue space may be associated with better mental health. However, very few studies have examined mechanisms. We examined associations between blue space proximity and a range of mental health outcomes and examined which of these associations were mediated by physical activity. METHODS: 350 participants (M = 38.74, SD = 14.92, 70% female) self-reported their weekly physical activity and completed measures of depression, anxiety, and psychological wellbeing. We then used GIS software to calculate blue space proximity (i.e., coastal and inland), and structural equation modelling with mediation paths to determine the role of physical activity in the associations between bluespace and mental health. RESULTS: Physical activity partially mediated the associations between coastal proximity and depression (ß = 0.02, 95% CI = 0.001, 0.05), anxiety (ß = 0.03, 95% CI = 0.01, 0.06), and wellbeing (ß = - 0.03, 95% CI = - 0.08, - 0.01), and fully mediated the associations between inland water proximity and depression (ß = 0.02, 95% CI = 0.003, 0.05), anxiety (ß = 0.03, 95% CI = 0.01, 0.07), and wellbeing (ß = - 0.03, 95% CI = - 0.07, - 0.01). CONCLUSION: While physical activity appears to explain associations between inland blue space and mental health outcomes, it only partially explains the association between coastal blue space and mental health, suggesting other mechanisms may play a role and even inactive exposure may be beneficial.

NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer.

Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1)-blockade immunotherapies have limited efficacy in the treatment of bladder cancer. Here, we show that NKG2A associates with improved survival and responsiveness to PD-L1 blockade immunotherapy in bladder tumors that have high abundance of CD8+ T cells. In bladder tumors, NKG2A is acquired on CD8+ T cells later than PD-1 as well as other well-established immune checkpoints. NKG2A+ PD-1+ CD8+ T cells diverge from classically defined exhausted T cells through their ability to react to human leukocyte antigen (HLA) class I-deficient tumors using T cell receptor (TCR)-independent innate-like mechanisms. HLA-ABC expression by bladder tumors is progressively diminished as disease progresses, framing the importance of targeting TCR-independent anti-tumor functions. Notably, NKG2A+ CD8+ T cells are inhibited when HLA-E is expressed by tumors and partly restored upon NKG2A blockade in an HLA-E-dependent manner. Overall, our study provides a framework for subsequent clinical trials combining NKG2A blockade with other T cell-targeted immunotherapies, where tumors express higher levels of HLA-E.

Depressive Symptoms and Drinking to Cope in Relation to Alcohol Use Outcomes among White and Black/African American College Students.

OBJECTIVE: Prior research shows that Black/African American adults experience more negative alcohol use consequences than White adults, despite lower alcohol consumption. Research also shows that Black/African Americans experience higher rates of depression, which can increase risk for alcohol consumption and alcohol use disorder (AUD) through drinking to cope. We examined associations between depressive symptoms and drinking to cope with alcohol consumption and AUD symptoms among White and Black/African American college students. METHODS: Participants completed an online survey during the fall and spring semester of their first year of college (N = 2,168, 62.8% female, 75.8% White). Path analyses were conducted to examine whether depressive symptoms and drinking to cope mediated the association between race/ethnicity and alcohol use outcomes, and whether race/ethnicity moderated the associations between depressive symptoms, drinking to cope, and alcohol use outcomes. RESULTS: Results indicated that Black/African Americans had lower levels of depressive symptoms, which were associated with lower drinking to cope, and in turn associated with lower alcohol consumption and AUD symptoms. Multigroup analysis indicated that the pattern of associations between depressive symptoms, drinking to cope, and alcohol use outcomes were largely similar between White and Black/African American college students and between males and females, except that the association between depressive symptoms and drinking to cope appeared to be stronger for Whites than for Black/African American students. CONCLUSION: Depressive symptoms and drinking to cope are risk factors in relation to alcohol use outcomes among White and Black/African American college students and partially account for the link between race/ethnicity and alcohol use outcomes.Supplemental data for this article is available online at https://doi.org/10.1080/10826084.2022.2034871 .

Development of a psychosocial oncology core curriculum for multidisciplinary education and training: Initial content validation using the modified Delphi Method.

OBJECTIVE: Despite its four decade history, the multidisciplinary specialty of psychosocial oncology (PSO) has no official consensus on core content. In 2014, the American Psychosocial Oncology Society (APOS) Board charged the APOS Professional Education Committee with outlining curricular content needed for core competence. METHODS: Content validation was completed using a four-phase modified Delphi Method. During Phase I, a Professional Education Committee subgroup proposed domains and items, which were rated by the APOS Fellows and Board via online survey. During Phase II, Fellows completed a second, revised survey. Phase III incorporated early career members. Developmental and diversity items were integrated into each domain. In Phase IV, a larger group of subject matter experts were surveyed, with feedback incorporated. Validation across phases involved average rating thresholds, intraclass correlations, and final percent agreement. RESULTS: The Delphi Method supported 12 content domains: Cancer Basics, Psychosocial Oncology, Professional Development, Ethics, Emotional/Psychological Concerns, Sexuality and Relationship Concerns, Spiritual/Religious Concerns, Healthcare Communication and Decision Making, Social/Practical Problems, Caregiver Concerns, Cognitive Concerns, Physical Symptoms and Psychosocial Assessment/Treatment. High levels of agreement were achieved across domains (86%-100%) and items, with no significant rating differences by discipline. CONCLUSIONS: This proposed core content can enhance and standardize education and training in PSO including APOS' Virtual Psychosocial Oncology Core Curriculum, focused on broadly expanding the PSO workforce, particularly in underserved areas. Next steps include development of core competencies and establishment of online training modules based on this content validation.

A probable case of leprosy from colonial period St. Vincent and the Grenadines, Southeastern Caribbean.

OBJECTIVE: To document and differentially diagnose facial pathology found in an isolated skull from St. Vincent and the Grenadines, southeastern Caribbean. To directly date this individual using radiocarbon dating. MATERIALS: Isolated skull recovered from Petite Mustique Island. METHODS: Describe facial pathology occurring in this individual and compare with known diseases or disease processes that impact the craniofacial complex. RESULTS: Features of the rhinomaxillary syndrome are present, indicating a diagnosis of leprosy. Dating places the time of death to the late 18th or early 19th centuries. CONCLUSIONS: Analysis of the rhinomaxillary syndrome produces a diagnosis of early-stage leprosy in an individual that correlates with the apparent attempt to locate a leprosarium on Petite Mustique Island in the first decade of the 19th century. SIGNIFICANCE: Location and time corroborate historical records of at least one attempt to locate a leprosarium on Petite Mustique Island. Only directly dated individual with leprosy in the western hemisphere and possibly the earliest yet recorded. LIMITATIONS: This is an isolated find that is archaeologically unprovenienced. SUGGESTIONS FOR FURTHER RESEARCH: Professional archaeological survey of Petite Mustique.

Quality of home spirometry performance amongst adults with cystic fibrosis.

Spirometry is usually performed under the supervision of a trained respiratory scientist to ensure acceptability and repeatability of results. To evaluate the quality of spirometry performance by adult cystic fibrosis (CF) patients with and without observation by a trained respiratory scientist, an observational, single centre study was conducted between February to December 2020. 74 adults were recruited and instructed to perform spirometry without supervision within 24 h of their remote CF clinic consultation. Spirometry was repeated at their consultation, supervised by a respiratory scientist using video conferencing. The majority of patients achieved grade A (excellent) or B (very good) spirometry quality with (95%) and without supervision (93%) independent of lung function severity. Similarly, forced expiratory volume in 1 second demonstrated no significant differences with paired spirometry performed within a 24 hour period. For a large proportion of adult CF patients, unsupervised portable spirometry produces acceptable and repeatable results.

From Bench to Bedside: How the Tumor Microenvironment Is Impacting the Future of Immunotherapy for Renal Cell Carcinoma.

Immunotherapy has revolutionized the treatment landscape for many cancer types. The treatment for renal cell carcinoma (RCC) has especially evolved in recent years, from cytokine-based immunotherapies to immune checkpoint inhibitors. Although clinical benefit from immunotherapy is limited to a subset of patients, many combination-based approaches have led to improved outcomes. The success of such approaches is a direct result of the tumor immunology knowledge accrued regarding the RCC microenvironment, which, while highly immunogenic, demonstrates many unique characteristics. Ongoing translational work has elucidated some of the mechanisms of response, as well as primary and secondary resistance, to immunotherapy. Here, we provide a comprehensive review of the RCC immunophenotype with a specific focus on how preclinical and clinical data are shaping the future of immunotherapy.

Uncialamycin-based antibody-drug conjugates: Unique enediyne ADCs exhibiting bystander killing effect.

Antibody-drug conjugates (ADCs) have emerged as valuable targeted anticancer therapeutics with at least 11 approved therapies and over 80 advancing through clinical trials. Enediyne DNA-damaging payloads represented by the flagship of this family of antitumor agents, N-acetyl calicheamicin [Formula: see text], have a proven success track record. However, they pose a significant synthetic challenge in the development and optimization of linker drugs. We have recently reported a streamlined total synthesis of uncialamycin, another representative of the enediyne class of compounds, with compelling synthetic accessibility. Here we report the synthesis and evaluation of uncialamycin ADCs featuring a variety of cleavable and noncleavable linkers. We have discovered that uncialamycin ADCs display a strong bystander killing effect and are highly selective and cytotoxic in vitro and in vivo.

Sexual Health and the LGBTQ+ Community.

Expand at first use ("lesbian, gay, bisexual, transgender, queer (or questioning), and others"? Sexual health is a state of physical, emotional, mental, and social well-being in relation to sexuality. Factors that contribute to the sexual health of an LGBTQ+-identified patient include not only the physical state of the patient but also cultural and contextual factors that influence other aspects of well-being. To be effective in promoting sexual health, providers must maintain an attitude of accepting the patient's sexual orientation and gender identity as core aspects of sexual health. Providers need to examine paperwork, office space, and cultural competence in providing a safe medical home for the LGBTQ+ community.

Social Isolation Among Older Adults in Long-Term Care: A Scoping Review.

Objectives: A wealth of literature has established risk factors for social isolation among older people; however, much of this research has focused on community-dwelling populations. Relatively little is known about how risk of social isolation is experienced among those living in long-term care (LTC) homes. We conducted a scoping review to identify possible risk factors for social isolation among older adults living in LTC homes. Methods: A systematic search of five online databases retrieved 1535 unique articles. Eight studies met the inclusion criteria. Results: Thematic analyses revealed that possible risk factors exist at three levels: individual (e.g., communication barriers), systems (e.g., location of LTC facility), and structural factors (e.g., discrimination). Discussion: Our review identified several risk factors for social isolation that have been previously documented in literature, in addition to several risks that may be unique to those living in LTC homes. Results highlight several scholarly and practical implications.

Design, Synthesis, and Biological Evaluation of Tubulysin Analogues, Linker-Drugs, and Antibody-Drug Conjugates, Insights into Structure-Activity Relationships, and Tubulysin-Tubulin Binding Derived from X-ray Crystallographic Analysis.

Molecular design, synthesis, and biological evaluation of tubulysin analogues, linker-drugs, and antibody-drug conjugates are described. Among the new discoveries reported is the identification of new potent analogues within the tubulysin family that carry a C11 alkyl ether substituent, rather than the usual ester structural motif at that position, a fact that endows the former with higher plasma stability than that of the latter. Also described herein are X-ray crystallographic analysis studies of two tubulin-tubulysin complexes formed within the α/ß interface between two tubulin heterodimers and two highly potent tubulysin analogues, one of which exhibited a different binding mode to the one previously reported for tubulysin M. The X-ray crystallographic analysis-derived new insights into the binding modes of these tubulysin analogues explain their potencies and provide inspiration for further design, synthesis, and biological investigations within this class of antitumor agents. A number of these analogues were conjugated as payloads with appropriate linkers at different sites allowing their attachment onto targeting antibodies for cancer therapies. A number of such antibody-drug conjugates were constructed and tested, both in vivo and in vitro, leading to the identification of at least one promising ADC (Herceptin-LD3), warranting further investigations.

The Effect of an Adsorbent Matrix on Recovery of Microorganisms from Hydrocarbon-Contaminated Groundwater.

The microbial degradation of recalcitrant hydrocarbons is an important process that can contribute to the remediation of oil and gas-contaminated environments. Due to the complex structure of subsurface terrestrial environments, it is important to identify the microbial communities that may be contributing to biodegradation processes, along with their abilities to metabolize different hydrocarbons in situ. In this study, a variety of adsorbent materials were assessed for their ability to trap both hydrocarbons and microorganisms in contaminated groundwater. Of the materials tested, a porous polymer resin (Tenax-TA) recovered the highest diversity of microbial taxa in preliminary experiments and was selected for additional (microcosm-based) testing. Oxic and anoxic experiments were prepared with groundwater collected from a contaminated aquifer to assess the ability of Tenax-TA to adsorb two environmental hydrocarbon contaminants of interest (toluene and benzene) while simultaneously providing a surface for microbial growth and hydrocarbon biodegradation. Microorganisms in oxic microcosms completely degraded both targets within 14 days of incubation, while anoxically-incubated microorganisms metabolized toluene but not benzene in less than 80 days. Community analysis of Tenax-TA-associated microorganisms revealed taxa highly enriched in sessile hydrocarbon-degrading treatments, including Saprospiraceae, Azoarcus, and Desulfoprunum, which may facilitate hydrocarbon degradation. This study showed that Tenax-TA can be used as a matrix to effectively trap both microorganisms and hydrocarbons in contaminated environmental systems for assessing and studying hydrocarbon-degrading microorganisms of interest.

Publication outcomes of abstracts presented at 2013 North American Congress of Clinical Toxicology (NACCT) conference.

Introduction: Scientific conferences are useful in disseminating medical research and advancing the medical and scientific fields. An important measure of the success of such conferences is the proportion of research that is published in peer-reviewed journals. The conversion rates for toxicology abstracts to full-text publications at previous North American toxicology meetings were low. No study has assessed the publication rate from the 2013 North American Congress of Clinical Toxicology (NACCT) conference.Methods: We reviewed 316 abstracts presented at the 2013 NACCT Conference. We searched the PubMed, EMBASE, and Medline databases using the authors' names and keywords, through September 2019. We then identified and excluded cases and case reports to reanalyze the data.Results: Thirty-three of 316 abstracts (10.4%) subsequently appeared in 17 different peer-reviewed journals, led by Clinical Toxicology (13 out of 33, 3%). Leading countries of origin for abstract submission were the USA (285), Canada (9), and the UK (8). Excluding case reports, 25 out of 207 abstracts (12.0%) achieved publication in peer-reviewed journals.Conclusions: Fewer than one in eight abstracts reached publication within six years of the 2013 NACCT meeting, even after accounting for and excluding case reports. This rate is lower than in other specialty medical societies.