Quality of Life in Patients and Their Spouses and Cohabitating Partners in the Year Following a Cancer Biopsy (the Couples Cope Study): Protocol for a Prospective Observational Study.

BACKGROUND: Receiving a diagnosis of cancer is a profound and often very stressful experience. Few studies have prospectively recruited patients prior to receiving a new diagnosis of cancer and included spouses or partners. OBJECTIVE: The aim of the Couples Cope Study is to understand the impact of undergoing a diagnostic biopsy and receiving a new cancer diagnosis on quality of life (QoL) in both patients and their spouses or partners, as well as on the quality of their relationship. This protocol paper describes the study design and assesses the feasibility of recruitment and retention. METHODS: Study staff reviewed the schedules of collaborating physicians using specific encounter codes to identify patients scheduled for breast or prostate biopsies. Potential participants were prescreened via the electronic health record and sent a recruitment letter at least 2 to 3 weeks prior to their biopsy procedure. Patients subsequently underwent a phone screening to determine eligibility. Patients who enrolled provided study staff with contact information for their spouses or partners. All consent forms were completed online. Surveys were completed online prior to receiving the biopsy results (baseline), and at 1, 3, 6, and 9 months after the biopsy. Study staff engaged in ongoing, personalized contact with participants and sent assessment completion reminders via phone and email. RESULTS: A total of 2294 patients undergoing a breast or prostate biopsy were identified and 69% (n=1582) were eligible for phone screening following electronic health record prescreening. Of the 431 patients who underwent phone screening, 75% (n=321) were eligible to participate. Of the eligible patients, 72% (n=231) enrolled and 82% (n=190) of enrolled patients had an accompanying partner or spouse who also enrolled. A total of 77% (34/44) of patients who received a cancer diagnosis and 72% (26/36) of their spouses or partners were retained through 9 months, while 80% (53/66) of patients who received a benign diagnosis and 68% (42/62) of their partners were retained. CONCLUSIONS: Prospective recruitment of patients undergoing diagnostic biopsy and their partners is feasible and requires both strategic collaboration with providers and concerted prescreening and recruitment efforts by study staff. Importantly, this study was able to conduct all study activities online without disrupting clinical workflow and without requiring patients and their spouses or partners to come into the laboratory. Consideration should be given to the ratio of biopsies to cancer diagnoses, which can vary significantly by cancer type. Prospective studies are needed and can inform our ability to provide effective support earlier to couples facing a possible cancer diagnosis. Future studies should examine other tumor types that have received less attention in QoL studies, include behavioral and neurobiological assessments beyond self-report measures, and follow couples beyond 9 months in order to examine long-term effects on QoL. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52361.

Surgical release of the chest wall skin and fascia for sclerodermatous graft versus host disease causing restrictive lung disease: A case report.

INTRODUCTION: Graft versus host disease (GVHD) remains a significant source of morbidity and mortality in the setting of allogeneic stem cell transplantation. Skin involvement is reported to be as high as 70-95 % in this group with GVHD and the severity of the involvement varies widely. Surgical management of complications of severe cutaneous GVHD is uncommon and is rarely mentioned as a treatment option. CASE PRESENTATION: We present a case of severe sclerodermatous skin changes restricting chest expansion and exercise tolerance to the point of limiting basic activities of daily life. A 54-year-old male presents with severe restrictive lung disease from sclerodermatous graft versus host disease (GVHD) after stem cell transplant for Chronic Myeloid Leukaemia (CML). He experienced limited symptomatic relief from maximal medical therapy and photochemotherapy, and subsequently underwent a skin release and split skin grafting of his chest and abdomen in an effort to improve exercise tolerance and quality of life. CLINICAL DISCUSSION: Despite an initial improvement in functioning, the patient's spirometry and lung function continued to decline with time, possibly suggesting that he did not gain a sustained benefit from surgical release of his cutaneous GVHD. CONCLUSION: While delineating between disease progression and surgical outcome is difficult in this case, the patient would argue that by delaying or reducing further decline in function, the surgical release procedures led to improved quality of life in subsequent years. However further research is required to establish a clear role for surgery in the treatment of refractory cutaneous GVHD.

The Importance of Social Support in Recovery Populations: Toward a Multilevel Understanding.

Although social support is commonly investigated in the context of substance recovery, researchers have widely neglected its multilevel nature, thus limiting what we know about its measurement across levels of observation. The current study used multilevel confirmatory factor analyses (MCFA) on 229 individuals living in 42 recovery homes to investigate the structure of single factor of social support at the individual and house-levels. Multilevel structural equation model (MSEM) was then conducted to examine whether the social support factor was associated with stress at the individual and house-levels. MCFA results showed that within individuals, all social support measures were significant and positive while at the house-level, there were a few discrepancies (e.g., IP was negative). Stress was significantly negatively related to the social support factor at the individual-level, but this association was positive at the house-level. These findings suggest that on an individual-level, a person's perception and source of social support is particularly important -even if the source of support comes from someone who is not abstinent. On a house-level, social support is more sensitive to outside influences than within individuals. Implications for future research and substance use interventions targeting social support are discussed.

Journey to wellness: A socioecological analysis of veterans in recovery from substance use disorders.

Substance use disorders are increasingly prevalent among veterans in the United States. Veterans in recovery face unique challenges, such as high rates of psychiatric comorbidities, difficulties adjusting to civilian life, and inadequate housing and mental health services. While prior research has explored veterans' experiences in recovery, studies have not implemented a multilevel perspective in their analyses. The current qualitative study examined how individual veteran experiences intersect with interpersonal and systemic factors. Semistructured focus groups were conducted with veterans who were former or current residents of recovery homes (N = 20). Thematic analysis was utilized to explore veterans' personal experiences through the CHIME-D framework (connectedness, hope & optimism, identity, meaning in life, empowerment, and difficulties). The data were further analyzed within a socioecological model (intrapersonal, interpersonal, and community). Each component of the CHIME-D framework was salient across all focus groups, with connectedness, empowerment, and difficulties being the most prominent themes that occurred across all socioecological levels. Results suggest that recovery initiatives can effectively assist veterans by promoting empowerment, facilitating social connections, and addressing cooccurring difficulties across multiple socioecological contexts. Additionally, treatment programs should encourage veterans to take on meaningful roles in their communities. Future research should continue to explore veterans' recovery experiences using a socioecological model.

Treatment of Experimental Autoimmune Encephalomyelitis with an Inhibitor of Phosphodiesterase-8 (PDE8).

After decades of development, inhibitors targeting cyclic nucleotide phosphodiesterases (PDEs) expressed in leukocytes have entered clinical practice for the treatment of inflammatory disorders, with three PDE4 inhibitors being in clinical use as therapeutics for psoriasis, psoriatic arthritis, chronic obstructive pulmonary disease and atopic dermatitis. In contrast, the PDE8 family that is upregulated in pro-inflammatory T cells is a largely unexplored therapeutic target. We have previously demonstrated a role for the PDE8A-Raf-1 kinase complex in the regulation of myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55) activated CD4+ effector T cell adhesion and locomotion by a mechanism that differs from PDE4 activity. In this study, we explored the in vivo treatment of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS) induced in mice immunized with MOG using the PDE8-selective inhibitor PF-04957325. For treatment in vivo, mice with EAE were either subcutaneously (s.c.) injected three times daily (10 mg/kg/dose), or were implanted subcutaneously with Alzet mini-osmotic pumps to deliver the PDE8 inhibitor (15.5 mg/kg/day). The mice were scored daily for clinical signs of paresis and paralysis which were characteristic of EAE. We observed the suppression of the clinical signs of EAE and a reduction of inflammatory lesion formation in the CNS by histopathological analysis through the determination of the numbers of mononuclear cells isolated from the spinal cord of mice with EAE. The PDE8 inhibitor treatment reduces the accumulation of both encephalitogenic Th1 and Th17 T cells in the CNS. Our study demonstrates the efficacy of targeting PDE8 as a treatment of autoimmune inflammation in vivo by reducing the inflammatory lesion load.

A Rare Case of Castrate-Resistant Prostate Adenocarcinoma with a Unilateral Testicular Metastasis Mimicking a Primary Testicular Tumour.

Prostate adenocarcinoma with testicular metastasis is rare, present in up to 4% of autopsy diagnoses, and presents symptomatically in less than 0.5% of cases. We report an unusual case of a 55-year-old male who developed a symptomatic testicular metastasis from primary prostate cancer 4 years after initial diagnosis of metastatic castrate-sensitive prostate cancer with nodal and bone-only involvement. The patient had orchidectomy, histologically confirming the metastasis and revealing sparing of the spermatic cord. Prior treatment for his metastatic castrate-sensitive prostate cancer had included androgen deprivation therapy and upfront docetaxel chemotherapy. He had received palliative radiotherapy for symptomatic bone metastasis and managed on enzalutamide for castrate-resistant disease for the preceding 22 months with ongoing PSA response at the time of diagnosis of new testicular metastasis, with a further significant PSA response following his "testicular metastasectomy." At the time of diagnosis of testicular metastasis, he did not have any evidence of other visceral metastases, and his metastatic disease otherwise remained radiologically stable. We describe his disease course, treatment and outline the rare nature of his case of testicular metastasis from prostate cancer.

The Effects of Using the Sun Safe App on Sun Health Knowledge and Behaviors of Young Teenagers: Results of Pilot Intervention Studies.

BACKGROUND: A balanced approach toward sun exposure and protection is needed by young people. Excessive sun exposure increases their risk for skin cancers such as melanoma, whereas some exposure is necessary for vitamin D and healthy bones. We have developed a new iOS smartphone app-Sun Safe-through a co-design process, which aims to support healthy and balanced decision-making by young teenagers (aged 12-13 years). OBJECTIVE: The aim of this study was to test the capacity of Sun Safe to improve sun health knowledge and behaviors of young teenagers in 3 pilot intervention studies completed in 2020. METHODS: Young teenagers (aged 12-13 years; N=57) were recruited through the web or through a local school via an open-access website and given access to Sun Safe (29/57, 51%) or a placebo (SunDial) app (28/57, 49%). Participants completed sun health questionnaires and knowledge quizzes before and after the 6-week intervention (either on the web or in class) and rated the quality of the app they used via a survey. RESULTS: Of the 57 participants, 51 (89%) participants (26, 51% for placebo arm and 25, 49% for the Sun Safe arm) completed these studies, with most (>50%) reporting that they used a smartphone to access their designated app either "once a fortnight" or "once/twice in total." Improved sun health knowledge-particularly about the UV Index-was observed in participants who were given access to Sun Safe compared with those who used the placebo (-6.2 [percentage correct] difference in predicted means, 95% CI -12.4 to -0.03; P=.049; 2-way ANOVA). Unexpectedly, there were significantly more sunburn events in the Sun Safe group (relative risk 1.7, 95% CI 1.1-1.8; P=.02; Fisher exact test), although no differences in time spent outdoors or sun-protective behaviors were reported. COVID-19 pandemic-related community-wide shutdowns during April 2020 (when schools were closed) reduced the time spent outdoors by >100 minutes per day (-105 minutes per day difference in predicted means, 95% CI -150 to -59 minutes per day; P=.002; paired 2-tailed Student t test). Sun Safe was well-rated by participants, particularly for information (mean 4.2, SD 0.6 out of 5). CONCLUSIONS: Access to the Sun Safe app increased sun health knowledge among young teenagers in these pilot intervention studies. Further investigations with larger sample sizes are required to confirm these observations and further test the effects of Sun Safe on sun-protective behaviors.

The Effect of Limiting the Scan Range of Computed Tomography Pulmonary Angiography (to Reduce Radiation Exposure) on the Detection of Pulmonary Embolism: A Systematic Review.

(1) Background: Computed tomography pulmonary angiography (CTPA) is the standard imaging test for the evaluation of acute pulmonary embolism (PE), but it is associated with patients' exposure to radiation. Studies have suggested that radiation exposure can be reduced without compromising PE detection by limiting the scan range (the z-axis, going from up to down); (2) Methods: A literature search was conducted in MEDLINE and EMBASE on 17 July 2021. Studies were included if they enrolled patients who had undergone a CTPA and described the yield of PE diagnoses, number of missed filling defects and/or other diagnoses using a reduced z-axis in comparison to a full-length scan. To assess risk of bias, we modified an existing risk of bias tools for observational studies, the Newcastle-Ottawa Scale. Results were synthesized in a narrative review. Primary outcomes were the number of missed PE diagnoses (based on at least one filling defect) and filling defects; the secondary outcome was the number of other missed findings; (3) Results: Eleven cohort studies and one case-control study were included reporting on a total of 3955 scans including 1025 scans with a diagnosis of PE. Six different reduced scan ranges were assessed; the most studied was from the top of the aortic arch to below the heart, in which no PEs were missed (seven studies). One sub-segmental PE was missed when the scan coverage was 10 cm starting from the bottom of the aortic arch and 14.7 cm starting from the top of the arch. Five studies that reported on other findings all found that other diagnoses were missed with a reduced z-axis. Most of the included studies had a high risk of bias; (4) Conclusions: CTPA scan coverage reduction from the top of aortic arch to below the heart reduced radiation exposure without affecting PE diagnoses, but studies were generally at high risk of bias.

"This Program Helped Save Our Lives so We All Can Bond over That": A Preliminary Study of the First Oxford House Collegiate Recovery Home.

College settings can be challenging environments for students recovering from substance use disorder. Collegiate Recovery Programs (CRP) have emerged on college campuses across the United States to help mitigate the risks recovering students face and to promote academic and recovery success. The current article describes the first collegiate recovery home to follow an Oxford House [OH] model, established at the University of North Carolina at Chapel Hill. In the present preliminary study, qualitative data were utilized to explore the strengths and challenges of this recovery model and students' experiences in the OH collegiate recovery home. Key stakeholders in the creation of this collegiate recovery home (n =2), as well as current and former student participants (n = 6), were interviewed. The key stake-holders' interviews revealed insights on the home's creation, modifications made from the traditional OH model, and the challenges faced in implementing a collegiate recovery home. Rapid qualitative analysis of the interviews of residents revealed salient themes that describe students' experiences within the collegiate recovery home: (1) resident social support, (2) connection to the student body, (3) anonymous status of the house, (4) lifestyle, (5) optimism, (6) self-independence, (7) Collegiate OH is essential for sobriety, and (8) UNC involvement and oversight. The implications of these findings for collegiate recovery homes are discussed, as well as suggestions for future studies.

Developing an Online Tool to Promote Safe Sun Behaviors With Young Teenagers as Co-researchers.

Despite education about the risks of excessive sun exposure, teenagers in Australia are sun-seeking, with sunburn common in summer. Conversely, some regular (time-limited) exposure to sunlight (that avoids sunburn) is necessary for vitamin D and healthy bones and other molecules important for immune and metabolic health. New interventions are thus required to better support teenagers to make healthy and balanced decisions about their sun behaviors. This paper describes the development of a prototype online tool-a smartphone app-that aimed to foster safe sun practices in teenagers. We recruited young adolescents (aged 12-13 years, n = 24) as "co-researchers" to provide ongoing input into the nature and design of the online tool. This age group was selected, as it is a critical time when young people transition from primary education, where "SunSmart" behaviors are entrenched in Australian schools, to high school, where risky behaviors emerge. Through a series of interviews and workshops, we codesigned an Apple iOS smartphone app with the co-researchers, leading health promotion professionals, researchers, and app designers. The developed app, Sun Safe, contains educational content relevant to teenagers about safe sun behaviors, complemented by other features requested by co-researchers and stakeholders to help engage young people, including gamified quizzes to test their sun health knowledge, real-time weather data on the UV Index and temperature, a sunscreen application timer, and reminders to check the UV Index. The developed prototype app was rated well by co-researchers, suggesting it is suitable for further feasibility and efficacy testing as an intervention tool to improve knowledge and promote safe sun behaviors by young adolescents.

Sun-health behaviours and attitudes towards sun safety amongst Australian teenagers: a qualitative update.

OBJECTIVE: This study aimed to explore current attitudes towards sun protection, and sun-seeking behaviour among young Australian adolescents. It was done as part of a larger project aiming to develop a digital resource to support young people in making informed sun-health decisions. RESULTS: Ten (4 male, 6 female) adolescents (12-13 years of age) living in Perth (Western Australia) were recruited through a social media-based strategy. Each participant engaged in a semi-structured telephone interview which explored their sun-health decision-making, with interview transcripts assessed qualitatively using NVivo. Three major themes (and eight sub-themes) were identified: (1) 'personal sun health considerations'; (2) 'attitudes towards sun protection'; and (3) 'recommendations'. The importance of sun protection was appreciated by participants. However, females were more diligent in the use of sun protection while males were indifferent. Behaviours were influenced by parental input, the school environment and engagement in sport. Adolescents had limited knowledge of the UV Index and its implications for sun protection, and the health importance of sun-derived vitamin D. Overall, the importance of sun protection was acknowledged but did not consistently translate into sun protective behaviours.

A catalogue of tools and variables from crisis and routine care to support decision-making about allocation of intensive care beds and ventilator treatment during pandemics: Scoping review.

PURPOSE: This scoping review sought to identify objective factors to assist clinicians and policy-makers in making consistent, objective and ethically sound decisions about resource allocation when healthcare rationing is inevitable. MATERIALS AND METHODS: Review of guidelines and tools used in ICUs, hospital wards and emergency departments on how to best allocate intensive care beds and ventilators either during routine care or developed during previous epidemics, and association with patient outcomes during and after hospitalisation. RESULTS: Eighty publications from 20 countries reporting accuracy or validity of prognostic tools/algorithms, or significant correlation between prognostic variables and clinical outcomes met our eligibility criteria: twelve pandemic guidelines/triage protocols/consensus statements, twenty-two pandemic algorithms, and 46 prognostic tools/variables from non-crisis situations. Prognostic indicators presented here can be combined to create locally-relevant triage algorithms for clinicians and policy makers deciding about allocation of ICU beds and ventilators during a pandemic. No consensus was found on the ethical issues to incorporate in the decision to admit or triage out of intensive care. CONCLUSIONS: This review provides a unique reference intended as a discussion starter for clinicians and policy makers to consider formalising an objective a locally-relevant triage consensus document that enhances confidence in decision-making during healthcare rationing of critical care and ventilator resources.

"It's like a Brotherhood": Thematic analysis of veterans' identity processes in substance abuse recovery homes.

This exploratory study aimed to understand how veterans' social identity influenced their experiences living in Oxford Houses (OH)-the largest network of substance use recovery homes in the United States. We conducted three focus groups, with 20 veterans who were current or former OH residents. Thematic analysis revealed several ways in which participants' veteran identity influenced their experiences living in OH, including: (1) thriving through OH organizational similarities with the military, (2) relationships with other OH residents, and (3) and growth and reintegration. The themes were interpreted using the Social Identity Theory and the Social Identity Model of Identity Change perspectives. Social identity processes were found to play an influential role in veterans' experiences in their recovery homes and reintegration into civilian life. Findings highlight the importance of veterans developing a community within a culturally congruent setting to facilitate their recovery from substance use disorders and adjustment to life post-military service.

Developing a Latent Coping Resources Factor for Recovery from Substance Use Disorder.

It is crucial for individuals with substance use disorders, especially those with a co-occurring mental health disorder, to access effective coping resources. We quantify coping through four domains of individual resources (self-esteem, self-efficacy, perceived social support, and hope) to examine the extent to which individuals with varying psychiatric severity can access coping-related resources. Since sex is an additionally important consideration in treatment, we also explore both sexes' access to coping-related resources. We generate a multilevel latent variable of coping resources in class structures, one for males and one for females, to measure (1) the extent individuals with varying psychiatric presentations (types, symptoms, severity) are able to access this latent resource and (2) to control for house level effects. Our variables of self-esteem, self-efficacy, perceived social support, and hope all coalesced into a latent variable, named coping resources. Furthermore, we find that psychiatric severity is negatively related to coping resources at the individual level, but function differently for males and females at the house level. Treatment guidelines should address the nuanced needs of individuals and consider individual differences, such as sex, that impact access to coping resources.

Circadian control of brain glymphatic and lymphatic fluid flow.

The glymphatic system is a network of perivascular spaces that promotes movement of cerebrospinal fluid (CSF) into the brain and clearance of metabolic waste. This fluid transport system is supported by the water channel aquaporin-4 (AQP4) localized to vascular endfeet of astrocytes. The glymphatic system is more effective during sleep, but whether sleep timing promotes glymphatic function remains unknown. We here show glymphatic influx and clearance exhibit endogenous, circadian rhythms peaking during the mid-rest phase of mice. Drainage of CSF from the cisterna magna to the lymph nodes exhibits daily variation opposite to glymphatic influx, suggesting distribution of CSF throughout the animal depends on time-of-day. The perivascular polarization of AQP4 is highest during the rest phase and loss of AQP4 eliminates the day-night difference in both glymphatic influx and drainage to the lymph nodes. We conclude that CSF distribution is under circadian control and that AQP4 supports this rhythm.

Developing a smartphone application to support social connectedness and wellbeing in young people with cystic fibrosis.

BACKGROUND: Young people with cystic fibrosis (CF) may be at increased risk of social isolation and mental illness. This study aimed to design and evaluate the usability and acceptability of a smartphone application (app) to support the social connectedness and wellbeing of young people living with CF. METHODS: Young people with CF aged 12-17 years (N = 22) were recruited from two paediatric hospitals in Australia. Study participants tested the CF app for six weeks before responding to an online survey about the app's usability and acceptability. A subsample of participants (n = 20) discussed the app's strengths and weaknesses during 11 online group interviews. RESULTS: During the six-week testing period, 77% of participants used the app at least once a week and 82% accessed the app from a smartphone. Usability of the CF app was rated high. Most participants agreed the app was easy to use (86%) and felt comfortable using it (96%). Acceptability of the app was moderate. 77% of participants agreed they would recommend the app to others. Recommendations to improve the app's functionality and acceptability included locating the chatroom within the app rather than redirecting users to a web browser and allowing users to personalise images, wellness tips and videos. CONCLUSIONS: This study developed and tested a highly usable, and moderately acceptable, smartphone app to improve the psychosocial health of young people living with CF. Future research will test the efficacy of the CF app on users' social connectedness and wellbeing.

Programmed cell death 1 protein and programmed death-ligand 1 inhibitors in the treatment of nonmelanoma skin cancer: A systematic review.

BACKGROUND: Immunotherapy using programmed cell death 1 protein (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors has been increasingly reported in a variety of nonmelanoma skin cancers (NMSCs). OBJECTIVE: To analyze the evidence of PD-1 and PD-L1 inhibitors in the treatment of NMSC. METHODS: A primary literature search was conducted with the PubMed, Cochrane Library, EMBASE, Web of Science, and CINAHL databases through October 28, 2018, to include studies on the use of PD-1 or PD-L1 inhibitors in patients for NMSC. Two reviewers independently performed study selection, data extraction, and critical appraisal. RESULTS: This systematic review included 51 articles. The most robust evidence was in the treatment of Merkel cell carcinoma and cutaneous squamous cell carcinomas, as supported by phase 1 and 2 clinical trials. Treatment of basal cell carcinoma, cutaneous sarcoma, sebaceous carcinoma, and malignant peripheral nerve sheath tumor also showed benefit with PD-1/PD-L1 inhibitors, but data are limited. There does not appear to be efficacy for PD-1/PD-L1 inhibitors in cutaneous lymphomas. LIMITATIONS: More investigation is needed to determine the efficacy, tumor responsiveness, and the safety profile of PD-1 and PD-L1 inhibitors in NMSC. CONCLUSION: PD-1 and PD-L1 inhibitors exhibit treatment efficacy in a variety of NMSCs.

Association between ribociclib and changes in creatinine in patients with hormone receptor positive metastatic breast cancer.

Combination ribociclib and aromatase inhibitors are currently the preferred treatment in Australia for newly diagnosed hormone receptor positive metastatic breast cancer in the absence of visceral crisis. In our case series of 32 patients, 28% experienced grade 1 elevations in creatinine, a toxicity that was under-recognised in large phase III studies. Creatinine rise appears to be due to a reversible inhibition of renal efflux transporters rather than an acute kidney injury in the majority of cases.