Preoperative inflammatory biomarkers reveal renal involvement in postsurgical mortality in hip fracture patients: an exploratory study.

Background: Hip fractures in frail patients result in excess mortality not accounted for by age or comorbidities. The mechanisms behind the high risk of mortality remain undetermined but are hypothesized to be related to the inflammatory status of frail patients. Methods: In a prospective observational exploratory cohort study of hospitalized frail hip fracture patients, 92 inflammatory markers were tested in pre-operative serum samples and markers were tested against 6-month survival post-hip fracture surgery and incidence of acute kidney injury (AKI). After correcting for multiple testing, adjustments for comorbidities and demographics were performed on the statistically significant markers. Results: Of the 92 markers tested, circulating levels of fibroblast growth factor 23 (FGF-23) and interleukin-15 receptor alpha (IL15RA), both involved in renal disease, were significantly correlated with 6-month mortality (27.5% overall) after correcting for multiple testing. The incidence of postoperative AKI (25.4%) was strongly associated with 6-month mortality, odds ratio = 10.57; 95% CI [2.76-40.51], and with both markers plus estimated glomerular filtration rate (eGFR)- cystatin C (CYSC) but not eGFR-CRE. The effect of these markers on mortality was significantly mediated by their effect on postoperative AKI. Conclusion: High postoperative mortality in frail hip fracture patients is highly correlated with preoperative biomarkers of renal function in this pilot study. The effect of preoperative circulating levels of FGF-23, IL15RA, and eGFR-CYSC on 6-month mortality is in part mediated by their effect on postoperative AKI. Creatinine-derived preoperative renal function measures were very poorly correlated with postoperative outcomes in this group.

National survey of patient perspectives on cost discussions among recipients of copay assistance.

BACKGROUND: Individuals with cancer and other medical conditions often experience financial concerns from high costs-of-care and may utilize copay assistance programs (CAP). We sought to describe CAP recipients' experiences/preferences for cost discussions with clinicians. METHODS: We conducted a national, cross-sectional electronic-survey from 10/2022 to 11/2022 of CAP recipients with cancer or autoimmune conditions to assess patient perspectives on cost discussions. We used multivariable logistic regression models to explore associations of patient perspectives on cost discussions with patient characteristics and patient-reported outcomes (eg, financial toxicity, depression/anxiety, and health literacy). RESULTS: Among 1,566 participants, 71% had cancer and 29% had autoimmune conditions. Although 62% of respondents desired cost discussions, only 32% reported discussions took place. Additionally, 52% of respondents wanted their doctor to consider out-of-pocket costs when deciding the best treatment, and 61% of respondents felt doctors should ensure patients can afford treatment prescribed. Participants with depression symptoms were more likely to want doctors to consider out-of-pocket costs (OR = 1.54, P = .005) and to believe doctors should ensure patients can afford treatment (OR = 1.60, P = .005). Those with severe financial toxicity were more likely to desire cost discussions (OR = 1.65, P < .001) and want doctors to consider out-of-pocket costs (OR = 1.52, P = .001). Participants with marginal/inadequate health literacy were more likely to desire cost discussions (OR = 1.37, P = .01) and believe doctors should ensure patients can afford treatment (OR = 1.30, P = .036). CONCLUSIONS: In this large sample of CAP recipients with cancer and autoimmune conditions, most reported a desire for cost discussions, but under one-third reported such discussions took place.

Early administration of umbilical cord blood cells following brief high tidal volume ventilation in preterm sheep: a cautionary tale.

BACKGROUND: Umbilical cord blood (UCB) cells are a promising treatment for preterm brain injury. Access to allogeneic sources of UCB cells offer the potential for early administration to optimise their therapeutic capacities. As preterm infants often require ventilatory support, which can contribute to preterm brain injury, we investigated the efficacy of early UCB cell administration following ventilation to reduce white matter inflammation and injury. METHODS: Preterm fetal sheep (0.85 gestation) were randomly allocated to no ventilation (SHAM; n = 5) or 15 min ex utero high tidal volume ventilation. One hour following ventilation, fetuses were randomly allocated to i.v. administration of saline (VENT; n = 7) or allogeneic term-derived UCB cells (24.5 ± 5.0 million cells/kg; VENT + UCB; n = 7). Twenty-four hours after ventilation, lambs were delivered for magnetic resonance imaging and post-mortem brain tissue collected. Arterial plasma was collected throughout the experiment for cytokine analyses. To further investigate the results from the in vivo study, mononuclear cells (MNCs) isolated from human UCB were subjected to in vitro cytokine-spiked culture medium (TNFα and/or IFNγ; 10 ng/mL; n = 3/group) for 16 h then supernatant and cells collected for protein and mRNA assessments respectively. RESULTS: In VENT + UCB lambs, systemic IFNγ levels increased and by 24 h, there was white matter neuroglial activation, vascular damage, reduced oligodendrocytes, and increased average, radial and mean diffusivity compared to VENT and SHAM. No evidence of white matter inflammation or injury was present in VENT lambs, except for mRNA downregulation of OCLN and CLDN1 compared to SHAM. In vitro, MNCs subjected to TNFα and/or IFNγ displayed both pro- and anti-inflammatory characteristics indicated by changes in cytokine (IL-18 & IL-10) and growth factor (BDNF & VEGF) gene and protein expression compared to controls. CONCLUSIONS: UCB cells administered early after brief high tidal volume ventilation in preterm fetal sheep causes white matter injury, and the mechanisms underlying these changes are likely dysregulated responses of the UCB cells to the degree of injury/inflammation already present. If immunomodulatory therapies such as UCB cells are to become a therapeutic strategy for preterm brain injury, especially after ventilation, our study suggests that the inflammatory state of the preterm infant should be considered when timing UCB cells administration.

Temporal Trends in Severe Brain Injury and Associated Outcomes in Very Preterm Infants.

INTRODUCTION: Severe brain injury (SBI), including severe intraventricular haemorrhage (sIVH) and cystic periventricular leukomalacia, poses significant challenges for preterm infants, yet recent data and trends are limited. METHODS: Analyses were conducted using the Australian and New Zealand Neonatal Network data on preterm infants born <32 weeks' gestation admitted at Monash Children's Hospital, Australia, from January 2014 to April 2021. The occurrence and trends of SBI and sIVH among preterm infants, along with the rates and trends of death and neurodevelopmental impairment (NDI) in SBI infants were assessed. RESULTS: Of 1,609 preterm infants, 6.7% had SBI, and 5.6% exhibited sIVH. A total of 37.6% of infants with SBI did not survive to discharge, with 92% of these deaths occurring following redirection of clinical care. Cerebral palsy was diagnosed in 65.2% of SBI survivors, while 86.4% of SBI survivors experienced NDI. No statistically significant differences were observed in the temporal trends of SBI (adjusted OR [95% CI] 1.08 [0.97-1.20]; p = 0.13) or sIVH (adjusted OR [95% CI] 1.09 [0.97-1.21]; p = 0.11). Similarly, there was no statistically significant difference noted in the temporal trend of the composite outcome, which included death or NDI among infants with SBI (adjusted OR [95% CI] 0.90 [0.53-1.53]; p = 0.71). CONCLUSION: Neither the rates of SBI nor its associated composite outcome of death or NDI improved over time. A notable proportion of preterm infants with SBI faced redirection of care and subsequent mortality, while most survivors exhibited adverse neurodevelopmental challenges. The development of better therapeutic interventions is imperative to improve outcomes for these vulnerable infants.

Neuroprotective effects of maternal melatonin administration in early-onset placental insufficiency and fetal growth restriction.

BACKGROUND: Early-onset fetal growth restriction (FGR) is associated with adverse outcomes. We hypothesised that maternal melatonin administration will improve fetal brain structure in FGR. METHODS: Surgery was performed on twin-bearing ewes at 88 days (0.6 gestation), and FGR induced in one twin via single umbilical artery ligation. Melatonin was administered intravenously (6 mg/day) to a group of ewes commencing on day of surgery until 127 days (0.85 gestation), when the ewe/fetuses were euthanized, and fetal brains collected. RESULTS: Study groups were control (n = 5), FGR (n = 5), control+melatonin (control+MLT; n = 6) and FGR+melatonin (FGR + MLT; n = 6). Melatonin administration did not significantly alter fetal body or brain weights. Myelin (CNPase+) fibre density was reduced in FGR vs. control animals in most brain regions examined (p < 0.05) and melatonin treatment restored CNPase fibre density. Similar but less pronounced effect was seen with mature myelin (MBP+) staining. Significant differences in activated microglia (Iba-1) activity were seen between lamb groups (MLT mitigated FGR effect) in periventricular white matter, subventricular zone and external capsule (p < 0.05). Similar effects were seen in astrogliosis (GFAP) in intragyral white matter and cortex. CONCLUSIONS: Maternal melatonin administration in early onset FGR led to improved myelination of white matter brain regions, possibly mediated by decreased inflammation. IMPACT: Maternal melatonin administration might lead to neuroprotection in the growth-restricted fetus, possibly via dampening neuroinflammation and enhancing myelination. This preclinical study adds to the body of work on this topic, and informs clinical translation. Neuroprotection likely to improve long-term outcomes of this vulnerable infant group.

Attitudes About the Human Papillomavirus Vaccine Among Patients With and Without Cervical Dysplasia.

OBJECTIVES: The aims of the study are to examine the perception of the human papillomavirus (HPV) vaccine among those with and without a history of cervical dysplasia and to examine perceptions of the vaccine for their children. MATERIALS AND METHODS: Patients were recruited to complete a survey about the HPV vaccine for both themselves and their children. Patients in a colposcopy clinic with a history of abnormal cervical cytology and patients in a benign gynecology clinic without a history of abnormal cervical cytology were recruited. Participants' medical records were reviewed. Demographics and survey answers were described, and Fisher exact test was used to compare the groups. RESULTS: One hundred eighty-three patients participated: 73 in colposcopy clinic and 110 in benign clinic. The majority self-identified as Black (74% colposcopy, 71% benign, p = .588) and reported an income less than $39,000 a year (77% colposcopy, 65% benign, p = .089). Fifty-six percent in benign clinic agreed the HPV vaccine is a good way to protect oneself from disease compared with 48% in colposcopy clinic ( p = .022). When examining results based on cytology, fewer patients in the highest-grade cytology group agreed the vaccine was effective (30% high-grade, 48% normal, 57% low-grade, p = .027) or a good way to protect themselves from disease (29% high-grade, 53% normal, 62% low-grade, p = .002). There was otherwise no statistically significant difference between the groups on questions regarding self or child vaccination. CONCLUSIONS: In a majority Black, low-income population, patients without a history of abnormal cervical cytology have more favorable perceptions of the HPV vaccine's effectiveness in preventing disease. Those with the highest-grade cytology had more negative perceptions of the vaccine's effectiveness and protectability.

Chatbot-interfaced and cognitive-affective barrier-driven messages to improve colposcopy adherence after abnormal Pap test results in underserved urban women: A feasibility pilot study.

Challenges in ensuring adherence to colposcopy and follow-up recommendations, particularly within underserved communities, hinder the delivery of appropriate care. Informed by our established evidence-based program, we sought to assess the feasibility and acceptability of a novel cognitive-affective intervention delivered through a Chatbot interface, aimed to enhance colposcopy adherence within an urban inner-city population. We developed the evidence-based intervention, CervixChat, to address comprehension of colposcopy's purpose, human papillomavirus (HPV) understanding, cancer-related fatalistic beliefs, procedural concerns, and disease progression, offered in both English and Spanish. Females aged 21-65, with colposcopy appointments at an urban OBGYN clinic, were invited to participate. Enrolled patients experienced real-time counseling messages tailored via a Chatbot-driven barriers assessment, dispatched via text one week before their scheduled colposcopy. Cognitive-affective measures were assessed at baseline and through a 1-month follow-up. Participants also engaged in a brief post-intervention satisfaction survey and interview to capture their acceptance and feedback on the intervention. The primary endpoints encompassed study adherence (CervixChat response rate and follow-up survey rate) and self-evaluated intervention acceptability, with predefined feasibility benchmarks of at least 70% adherence and 80% satisfaction. Among 48 eligible women scheduled for colposcopies, 27 (56.3%) agreed, consented, and completed baseline assessments. Participants had an average age of 34 years, with 14 (52%) identifying as non-Hispanic White. Of these, 21 (77.8%) engaged with the CervixChat intervention via mobile phones. Impressively, 26 participants (96.3%) attended their diagnostic colposcopy within the specified timeframe. Moreover, 22 (81.5%) completed the follow-up survey and a brief interview. Barriers assessment revealed notable encodings in the Affect and Values/Goals domains, highlighting concerns and understanding around HPV, as well as its impact on body image and sexual matters. Persistent and relatively high intrusive thoughts and lowered risk perceptions regarding cervical cancer were reported over time, unaffected by the intervention. Post-intervention evaluations documented high satisfaction and perceived usefulness, with recommendations for incorporating additional practical and educational content. Our findings underscore the robust satisfaction and practicality of the CervixChat intervention among a diverse underserved population. Moving forward, our next step involves evaluating the intervention's efficacy through a Sequential Multiple Assignment Randomized Trial (SMART) design. Enhanced by personalized health coaching, we aim to further bolster women's risk perception, address intrusive thoughts, and streamline resources to effectively improve colposcopy screening attendance.

Our study focused on helping underserved women, especially from ethnic minorities, with abnormal Pap test results. We aimed to break down barriers preventing them from seeking necessary follow-up care. Using Chatbot-facilitated text messages, we reached out to offer timely support. Starting with a warm text, we asked participants to share their thoughts on their abnormal Pap results. We then sent targeted messages addressing concerns about colposcopy, cervical health, emotions, appointment importance, and coping strategies. Participants engaged actively, finding value in the messages for information and encouragement. Their responses highlighted concerns about the test and emotional challenges. We also identified the need to address worries about human papillomavirus (HPV), body image, and discomfort during the test. In conclusion, our study showcased the feasibility and acceptability of using Chatbot messages to provide tailored support after abnormal Pap tests. By addressing unique concerns, we aimed to alleviate distress and enhance adherence to follow-up care for better cervical cancer screening outcomes.

Perceived importance of weight loss and exercise among endometrial cancer survivors with overweight or obesity: Implications for lifestyle modification interventions.

Objective: Type 1 endometrial cancer (EC) survivors who are overweight or obese are at increased risk of comorbidities and reduced quality of life. Lifestyle modification interventions (e.g., healthy eating, exercise) may help these women reduce excess weight and improve their quality of life. However, existing interventions have shown limited success. Guided by Self-Determination Theory, the proposed study sought to identify factors associated with perceived importance of weight loss and exercise as well as interest in lifestyle modification interventions (components of extrinsic and intrinsic motivation) among EC survivors with overweight or obesity to inform future intervention development. Methods: One hundred type 1 EC survivors [body mass index (BMI) ≥ 25 kg/m2] completed a cross-sectional survey assessing sociodemographics, medical factors, exercise, risk perceptions and provider communication, quality of life, barriers to dieting and exercise, perceived importance of healthy lifestyles, and desired intervention content. Results: EC survivors who were aware obesity is a risk factor for EC were significantly more likely to perceive weight loss as important and were interested in weight loss programs and receiving information about exercise (ps < 0.05). Additionally, EC survivors who reported their provider discussed the importance of a healthy weight after their diagnosis were significantly more likely to perceive exercise as important and were interested in receiving dieting information. Conclusions: EC survivors expressed interest in lifestyle modification interventions. Increasing awareness about the risk of obesity and provider discussions about healthy weight during routine appointments may motivate EC survivors to engage in lifestyle modification interventions.

The lived experience of patients with breast cancer on adjuvant endocrine therapy: side effects and coping strategies during the first year of medication initiation.

PURPOSE: Adjuvant endocrine therapy (AET) is pivotal for hormone receptor-positive breast cancer patients, significantly enhancing survival rates. Yet, adherence to AET remains challenging due to side effects. This study delves into the lived experience of breast cancer survivors concerning AET-induced side effects and examines differences in symptom profiles between Tamoxifen and aromatase inhibitors (AIs). METHODS: We interviewed 35 breast cancer survivors on AET, conducting qualitative iterative analysis using grounded theory. A codebook was developed to aid data coding and interpretation. NVIVO software facilitated comprehensive transcript analysis. RESULTS: Survivors reported a spectrum of side effects like hot flashes, sexual issues, joint pain, stiffness, mood swings, and fertility concerns. Symptom profiles differed based on AET type. Tamoxifen users experienced more frequent sexual side effects and mood swings, while AIs were linked to joint pain, stiffness, and bone health worries. Those on AET for over 6 months expressed heightened concerns about side effects. CONCLUSION: Tailored patient education, aligned with AET type, empowers survivors to manage side effects using self-regulatory strategies. Acknowledging distinct symptom profiles enables informed decisions, improving adherence and quality of life. IMPLICATIONS: This study underscores tailored survivorship support, equipping patients with tools to manage side effects, enhancing adherence, and long-term outcomes. The findings inform the integration of comprehensive survivorship programs, emphasizing individualized strategies for managing side effects and promoting better adherence and improved quality of life.

Preference Elicitation and Treatment Decision-Making Among Men Diagnosed With Prostate Cancer: Randomized Controlled Trial Results of Healium.

BACKGROUND: Elicitation of patients' preferences is an integral part of shared decision-making, the recommended approach for prostate cancer decision-making. Existing decision aids for this population often do not specifically focus on patients' preferences. Healium is a brief interactive web-based decision aid that aims to elicit patients' treatment preferences and is designed for a low health literate population. OBJECTIVE: This study used a randomized controlled trial to evaluate whether Healium, designed to target preference elicitation, is as efficacious as Healing Choices, a comprehensive education and decision tool, in improving outcomes for decision-making and emotional quality of life. METHODS: Patients diagnosed with localized prostate cancer who had not yet made a treatment decision were randomly assigned to the brief Healium intervention or Healing Choices, a decision aid previously developed by our group that serves as a virtual information center on prostate cancer diagnosis and treatment. Assessments were completed at baseline, 6 weeks, and 3 months post baseline, and included decisional outcomes (decisional conflict, satisfaction with decision, and preparation for decision-making), and emotional quality of life (anxiety/tension and depression), along with demographics, comorbidities, and health literacy. RESULTS: A total of 327 individuals consented to participate in the study (171 were randomized to the Healium intervention arm and 156 were randomized to Healing Choices). The majority of the sample was non-Hispanic (272/282, 96%), White (239/314, 76%), married (251/320, 78.4%), and was on average 62.4 (SD 6.9) years old. Within both arms, there was a significant decrease in decisional conflict from baseline to 6 weeks postbaseline (Healium, P≤.001; Healing Choices, P≤.001), and a significant increase in satisfaction with one's decision from 6 weeks to 3 months (Healium, P=.04; Healing Choices, P=.01). Within both arms, anxiety/tension (Healium, P=.23; Healing Choices, P=.27) and depression (Healium, P=.001; Healing Choices, P≤.001) decreased from baseline to 6 weeks, but only in the case of depression was the decrease statistically significant. CONCLUSIONS: Healium, our brief decision aid focusing on treatment preference elicitation, is as successful in reducing decisional conflict as our previously tested comprehensive decision aid, Healing Choices, and has the added benefit of brevity, making it the ideal tool for integration into the physician consultation and electronic medical record. TRIAL REGISTRATION: ClinicalTrials.gov NCT05800483; https://clinicaltrials.gov/study/NCT05800483.

Allogeneic Cell Therapy Applications in Neonates: A Systematic Review.

BACKGROUND: Neonatal cell therapy applications are increasing; however, data on allogeneic cell therapy are limited. OBJECTIVE: To summarize evidence on allogeneic cell therapy in term and preterm neonates. METHODS: Cochrane Central Register of Controlled Trials, Embase, Ovid Medline, and various registries were searched for studies investigating the safety, feasibility, and efficacy of allogeneic cell therapy in neonates. Two authors independently selected the articles, extracted data, and assessed the risk of bias. RESULTS: Twelve published (153 infants) and 21 ongoing studies were included. These studies predominantly sourced allogeneic cells from umbilical cord blood (UCB). Mesenchymal stromal cells (MSCs) were the main cell type used (134 of 153 infants); others included UCB-derived total nucleated cells (TNCs) and human amnion epithelial cells (hAECs). Applications included bronchopulmonary dysplasia (BPD; 113 infants), Krabbe disease (13 infants), intraventricular haemorrhage (10 infants), perinatal arterial ischemic stroke (10 infants), hypoxic-ischaemic encephalopathy (6 infants), and necrotizing enterocolitis (1 infant). Nine out of 12 studies did not report any serious adverse events (SAEs) related to cell administration. Three studies reported SAEs, such as graft versus host disease (GVHD) in 5 infants (UCB-derived TNCs for Krabbe disease); and transient cardiorespiratory compromise in 1 infant (hAECs for BPD). Data on efficacy outcomes were limited. CONCLUSION: The safety and feasibility of allogeneic cell therapy applications in neonates are available, mainly from the use of MSCs. Further safety data for other cell types are required, and the risk of GVHD in different settings needs to be determined. Efficacy studies are largely lacking for all cell types. PROTOCOL REGISTRATION: The protocol was registered with PROSPERO (registration number CRD42023397876), the international prospective register for systematic reviews (https://www.crd.york.ac.uk/PROSPERO).

Feasibility and Acceptability of an Online Oncologist Training to Optimize Oncologist-Patient Communication and Value-Concordant Care in Advanced Cancer.

Introduction: This pilot study tested the feasibility and acceptability of a low-resource-intensive scalable online communication training designed to improve oncologists' skills in prognostic and value-concordant care discussions with advanced cancer patients. Methods: The training consisted of on-demand videos on how to convey prognostic information, manage patient emotions, and elicit patient values and incorporate these values into treatment decision making. Post-intervention, oncologists reported on their perceptions of the training. Results: Fifteen oncologists were enrolled, of whom, 13 completed the training, and 14 completed post-intervention interviews. Most oncologists reported the intervention was acceptable: 92.9% indicated the intervention was "moderately" to "very helpful"; 78.6% rated it as "somewhat" to "very much" impactful on their communication with patients. Conclusions: The present self-paced online communication training was acceptable to oncologists, supporting additional research, including evaluating intervention efficacy for improving oncologists' communication skills and value-concordant care in advanced cancer.

Examining the impact of a multimedia intervention on decisional conflict and psychological distress among early-stage breast cancer patients: results from a nationwide RCT.

We conducted a nationwide, randomized controlled trial to evaluate the impact of Healing Choices, a novel interactive education and treatment decision program rooted in the self-regulation theory framework, on decisional conflict and psychological distress at 2-month post-intervention in women with early-stage breast cancer. Patients were randomized to receive the National Cancer Institute's standard print material (control) or standard print material plus Healing Choices (the intervention). The final sample at 2-month post-intervention consisted of N = 388 participants (intervention: n = 197; control: n = 191). There were no significant differences in decisional conflict or its subscales; however, psychological distress was higher in the intervention group (16.09 ± 10.25) than in the control group (14.37 ± 8.73) at follow-up, B = 1.88, 95% CI [-0.03, 3.80], t(383) = 1.94, p = .05. Upon further examination, we found that engagement with the intervention was low-41%-prompting as-treated analyses, which showed no difference in distress between users and nonusers and a positive impact of Healing Choices on decisional conflict: decisional support subscale: users (35.36 ± 15.50) versus nonusers (39.67 ± 15.99), B = -4.31 (s.e. = 2.09), p = .04. Multiple recommendations for moving ahead stem from this work: (i) intent-to-treat analyses appeared to cause distress, cautioning against interventions that may lead to information overload; (ii) engagement with the intervention is low and future work needs to focus on increasing engagement and monitoring it throughout the study; and (iii) in studies with low engagement, as-treated analyses are critical.

Healing Choices is a multimedia software program that provides information and decision-making support for women with early-stage breast cancer. We present the results of a randomized controlled trial that evaluated the impact of Healing Choices, compared with standard of care (National Cancer Institute's standard print material), on decisional conflict and psychological distress. In total, 388 participants (197 in the intervention and 191 in the control group) completed the 2-month post-intervention assessment. Results indicated that Healing Choices did not help with treatment decision-making but was associated with higher levels of psychological distress. Use among women assigned to Healing Choices, however, was low, at 41%. When comparing women who used the program with those who did not, we found that the effect of elevated distress disappeared, while program users felt more support than nonusers during the decision-making process. In the future, interventions such as Healing Choices should be regulated so as not to cause distress via information overload, a focus on monitoring and increasing engagement with the intervention is necessary, and, when engagement is low, as-treated analyses are critical to explore the efficacy of the intervention.

Cancer Resource and Information Support (CRIS) for Bladder Cancer Survivors and Their Caregivers: Development and Usability Testing Study.

BACKGROUND: Bladder cancer survivors and their caregivers face profound practical (eg, use of stoma appliances and care for urinary diversion methods) and psychosocial (eg, depression and anxiety) challenges after surgical treatment with cystectomy. OBJECTIVE: To improve the health-related quality of life and postsurgical outcomes of both bladder cancer survivors and their caregivers, the team, in collaboration with Sourcetop, Inc (software design) and Dappersmith (graphic design), developed the Cancer Resource and Information Support (CRIS) software. The purpose of this manuscript is to report on the development and usability testing of the CRIS software. METHODS: The development of the CRIS software was guided by the Obesity-Related Behavioral Intervention Trials (ORBIT) model for developing behavioral treatments for chronic diseases. The ORBIT model is unique in that it proposes a flexible and progressive process with prespecific clinically significant milestones for forward movement and returns to earlier stages for refinement, and it facilitates communication among diverse groups by using terminology from the drug development model. This paper focuses on 2 phases of the ORBIT model: phase IA: define and IB: refine. During phase IA, the study team developed solutions for the stated clinical problem-adjustment to life post cystectomy-by reviewing the literature and collecting feedback from clinicians, professional organizations, bladder cancer survivors, and their caregivers. During Phase IB, the study team focused on tailoring content in the CRIS software to the user as well as usability testing with 7 participants. RESULTS: The finished product is CRIS, a web-based software for survivors of bladder cancer and their caregivers to serve as a health management and lifestyle resource after surgery. Overarching themes from phase IA (participant feedback) included how to use new medical equipment, tips and tricks for easier living with new medical equipment, questions about health maintenance, and questions about lifestyle modifications. To accommodate our target population, we also incorporated recommendations from the Americans with Disabilities Act for website design, such as large text size, large paragraph spacing, highly contrasting text and background colors, use of headings and labels to describe the purpose of the content, portrait orientation without the need for horizontal scrolling, multiple ways to access a web page within a set of pages, ability to navigate web pages in sequential order, and in-text links that are descriptive. Usability participants evaluated CRIS very positively, indicating that it was easy to use, the functions were well-integrated, and if available, they would use CRIS frequently. CONCLUSIONS: CRIS, developed over the course of 18 months by integrating feedback from experts, literature reviews, and usability testing, is the first web-based software developed for bladder cancer survivors and their caregivers to help them adjust to life following cystectomy. The efficacy of CRIS in improving patients' and caregivers' quality of life is currently being evaluated in a randomized controlled trial.

Confusion and anxiety in between abnormal cervical cancer screening results and colposcopy: "The land of the unknown".

OBJECTIVE: Attendance to colposcopy after abnormal cervical cancer screening is essential to cervical cancer prevention. This qualitative study explored patients' understanding of screening results, their experiences of the time leading up to the colposcopy appointment, and colposcopy. METHODS: We recruited women referred for colposcopy from two urban practices in an academic health system. Individual interviews (N = 15) with participants were conducted after colposcopy appointments about their cervical cancer screening histories, current results, and colposcopy experiences. A team analyzed and summarized interviews and coded transcripts in Atlas.ti. RESULTS: We found that most women were confused about their screening results, did not know what a colposcopy was before being referred for one, and experienced anxiety in the interval between receiving their results and having their colposcopy. Most women searched for information online, but found "misinformation," "worst-case scenarios" and generic information that did not resolve their confusion. CONCLUSION: Women had little understanding of their cervical cancer risk and experienced anxiety looking for information and waiting for the colposcopy. Educating patients about cervical precancer and colposcopy, providing tailored information about their abnormal screening test results and potential next steps, and helping women manage distress may alleviate uncertainty while waiting for follow-up appointments. PRACTICE IMPLICATIONS: Interventions to manage uncertainty and distress in the interval between receiving an abnormal screening test result and attending colposcopy are needed, even among highly adherent patients.

The lived experience of breast cancer patients on adjuvant endocrine therapy: Side effects and coping strategies during the first year of medication initiation.

Purpose: Breast cancer in women is the most commonly diagnosed cancer. Adjuvant endocrine therapy (AET) showed consistent improvements in recurrence and survival rates. Adherence to adjuvant endocrine therapy remains essential for improving overall survival in women with hormone receptor (HR) positive breast cancer. However, early discontinuation of medicine is reported to range from 20% to 50%. Poor adherence has been attributed to multiple factors including presence of adverse events. We aim to report the lived experience of breast cancer survivors specifically as regards to side effects, the most reported reason for lack of adherence. Methods: 35 breast cancer survivors on AET were interviewed. Qualitative iterative analysis was conducted using the grounded theory approach with the goal of identifying themes that emerge from the interviews and refining the question probes as needed. A codebook was developed and supplemented with interpretive codes generated through ongoing analysis of transcripts. All transcripts were coded using NVIVO qualitative data analysis software for data interpretations. Results: Reported side effects associated with AET medications include hot flashes, sexual side-effects, joint pain, stiffness, cognitive function, mood changes, bone mass density decrease and fertility concerns. Women who were on AET more than 6 months reported more side effect concerns. A variety of coping strategies using over the counter medications or alternative medicines and approaches were also discussed. Conclusion: Tailored and timely information on potential AET-induced side effects and strategies to manage them is needed. In particular, some side effects are more prevalent by medication (e.g., joint pain in those who were taking an aromatases inhibitor). Provision of information to prepare women for the potential side effects of type of AET they are prescribed for would be helpful. Implications for Cancer Survivors: As AET has been suggested for 10 years to improve surveillance and reduce recurrence, our results have implications for cancer survivors, especially the onsets of side effects and potential ways to manage them as they arise.

Endothelial colony forming cell administration promotes neurovascular unit development in growth restricted and appropriately grown fetal lambs.

BACKGROUND: Fetal growth restriction (FGR) is associated with deficits in the developing brain, including neurovascular unit (NVU) dysfunction. Endothelial colony forming cells (ECFC) can mediate improved vascular stability, and have demonstrated potential to enhance vascular development and protection. This investigation examined whether ECFCs from human umbilical cord blood (UCB) enhanced NVU development in FGR and appropriate for gestational age (AGA) fetal sheep. METHODS: Twin-bearing ewes had surgery performed at 88-90 days' gestation, inducing FGR in one fetus. At 113 days, ECFCs (1 × 107 cells) cultured from human UCB were administered intravenously to fetal sheep in utero. At 127 days, ewes and their fetuses were euthanised, fetal brains collected, and NVU components analysed by immunohistochemistry. RESULTS: Twenty-four fetal lambs, arranged in four groups: AGA (n = 7), FGR (n = 5), AGA + ECFC (n = 6), and FGR + ECFC (n = 6), were included in analyses. FGR resulted in lower body weight than AGA (P = 0.002) with higher brain/body weight ratio (P = 0.003). ECFC treatment was associated with increased vascular density throughout the brain in both AGA + ECFC and FGR + ECFC groups, as well as increased vascular-astrocyte coverage and VEGF expression in the cortex (P = 0.003, P = 0.0006, respectively) and in the subcortical white matter (P = 0.01, P = 0.0002, respectively) when compared with the untreated groups. CONCLUSIONS: ECFC administration enhanced development of NVU components in both the AGA and FGR fetal brain. Further investigation is required to assess how to optimise the enhanced angiogenic capabilities of ECFCs to provide a therapeutic strategy to protect the developing NVU against vulnerabilities associated with FGR.

Factors Influencing the Efficacy of Umbilical Cord Blood-Derived Cell Therapy for Perinatal Brain Injury.

INTRODUCTION: We have previously described preclinical literature which supports umbilical cord blood-derived cell (UCBC) therapy as an efficacious treatment for perinatal brain injury. However, efficacy of UCBCs may be influenced by different patient population and intervention characteristics. OBJECTIVES: To systematically review the effects of UCBCs on brain outcomes in animal models of perinatal brain injury across subgroups to better understand the contribution of model type (preterm versus term), brain injury type, UCB cell type, route of administration, timing of intervention, cell dosage, and number of doses. METHODS: A systematic search of MEDLINE and Embase databases was performed to identify studies using UCBC therapy in animal models of perinatal brain injury. Subgroup differences were measured by chi2 test where possible. RESULTS: Differential benefits of UCBCs were seen across a number of subgroup analyses including intraventricular hemorrhage (IVH) vs. hypoxia ischemia (HI) model (apoptosis white matter (WM): chi2 = 4.07; P = .04, neuroinflammation-TNF-α: chi2 = 5.99; P = .01), UCB-derived mesenchymal stromal cells (MSCs) vs. UCB-derived mononuclear cells (MNCs) (oligodendrocyte WM: chi2 = 5.01; P = .03, neuroinflammation-TNF-α: chi2 = 3.93; P = .05, apoptosis grey matter (GM), astrogliosis WM), and intraventricular/intrathecal vs. systemic routes of administration (microglial activation GM: chi2 = 7.51; P = .02, astrogliosis WM: chi2 = 12.44; P = .002). We identified a serious risk of bias and overall low certainty of evidence. CONCLUSIONS: Preclinical evidence suggests UCBCs to show greater efficacy in the injury model of IVH compared to HI, the use of UCB-MSCs compared to UCB-MNCs and the use of local administrative routes compared to systemic routes in animal models of perinatal brain injury. Further research is needed to improve certainty of evidence and address knowledge gaps.

Lack of Neuroprotection with a Single Intravenous Infusion of Human Amnion Epithelial Cells after Severe Hypoxia-Ischemia in Near-Term Fetal Sheep.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) around the time of birth results from loss of oxygen (hypoxia) and blood supply (ischemia). Exogenous infusion of multi-potential cells, including human amnion epithelial cells (hAECs), can reduce hypoxic-ischemic (HI) brain injury. However, there are few data on treatment of severe HI in large animal paradigms at term. The aim of the current study was to determine whether infusion of hAECs early after injury may reduce brain damage after ischemia in near-term fetal sheep. METHODS: Chronically instrumented fetal sheep (0.85 gestation) received 30 min of global cerebral ischemia followed by intravenous infusion of hAECs from 2 h after the end of ischemia (ischemia-hAEC, n = 6) or saline (ischemia-vehicle, n = 7). Sham control animals received sham ischemia with vehicle infusion (sham control, n = 8). RESULTS: Ischemia was associated with significant suppression of EEG power and spectral edge frequency until the end of the experiment and a secondary rise in cortical impedance from 24 to 72 h, which were not attenuated by hAEC administration. Ischemia was associated with loss of neurons in the cortex, thalamus, striatum and hippocampus, loss of white matter oligodendrocytes and increased microglial numbers in the white matter, which were not affected by hAEC infusion. CONCLUSIONS: A single intravenous administration of hAECs did not reduce electrographic or histological brain damage after 30 min of global cerebral ischemia in near-term fetal sheep.