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In EGFR-mutated lung cancer, the duration of response to tyrosine kinase inhibitors (TKIs) is limited by the development of acquired drug resistance. Despite the crucial role played by apoptosis-related genes in tumor cell survival, how their expression changes as resistance to EGFR-TKIs emerges remains unclear. Here, we conduct a comprehensive analysis of apoptosis-related genes, including BCL-2 and IAP family members, using single-cell RNA sequence (scRNA-seq) and spatial transcriptomics (ST). scRNA-seq of EGFR-mutated lung cancer cell lines captures changes in apoptosis-related gene expression following EGFR-TKI treatment, most notably BCL2L1 upregulation. scRNA-seq of EGFR-mutated lung cancer patient samples also reveals high BCL2L1 expression, specifically in tumor cells, while MCL1 expression is lower in tumors compared to non-tumor cells. ST analysis of specimens from transgenic mice with EGFR-driven lung cancer indicates spatial heterogeneity of tumors and corroborates scRNA-seq findings. Genetic ablation and pharmacological inhibition of BCL2L1/BCL-XL overcome or delay EGFR-TKI resistance. Overall, our findings indicate that BCL2L1/BCL-XL expression is important for tumor cell survival as EGFR-TKI resistance emerges.
Subject(s)
Apoptosis , ErbB Receptors , Lung Neoplasms , Mutation , Single-Cell Analysis , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Lung Neoplasms/drug therapy , ErbB Receptors/metabolism , ErbB Receptors/genetics , Humans , Apoptosis/genetics , Apoptosis/drug effects , Animals , Mice , Mutation/genetics , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , RNA-Seq , Transcriptome/genetics , Drug Resistance, Neoplasm/genetics , Protein Kinase Inhibitors/pharmacology , Mice, Transgenic , Gene Expression Profiling , bcl-X Protein/metabolism , bcl-X Protein/genetics , Single-Cell Gene Expression AnalysisABSTRACT
BACKGROUND: Regulatory and professional nursing associations have an important role in ensuring that nurses provide safe, competent, and ethical care and are capable of adapting to emerging phenomena that influence society and population health needs. Telehealth and more recently virtual care are 2 digital health modalities that have gained momentum during the COVID-19 pandemic. Telehealth refers to telecommunications and digital communication technologies used to deliver health care, support health care provider and patient education, and facilitate self-care. Virtual care facilitates the delivery of health care services via any remote communication between patients and health care providers and among health care providers, either synchronously or asynchronously, through information and communication technologies. Despite nurses' adaptability to delivering virtual care, many have also reported challenges. OBJECTIVE: This study aims to describe resources about virtual care, digital health, and nursing informatics (ie, practice guidelines and fact sheets) available to Canadian nurses through their regulatory and professional associations. METHODS: An environmental scan was conducted between March and July 2023. The websites of nursing regulatory bodies across 13 Canadian provinces and territories and relevant nursing and a few nonnursing professional associations were searched. Data were extracted from the websites of these organizations to map out educational materials, training opportunities, and guidelines made available for nurses to learn and adapt to the ongoing digitalization of the health care system. Information from each source was summarized and analyzed using an inductive content analysis approach to identify categories and themes. The Virtual Health Competency Framework was applied to support the analysis process. RESULTS: Seven themes were identified: (1) types of resources available about virtual care, (2) terminologies used in virtual care resources, (3) currency of virtual care resources identified, (4) requirements for providing virtual care between provinces, (5) resources through professional nursing associations and other relevant organizations, (6) regulatory guidance versus competency in virtual care, and (7) resources about digital health and nursing informatics. Results also revealed that practice guidance for delivering telehealth existed before the COVID-19 pandemic, but it was further expanded during the pandemic. Differences were noted across available resources with respect to terms used (eg, telenursing, telehealth, or virtual care), types of documents (eg, guideline vs fact sheet), and the depth of information shared. Only 2 associations provided comprehensive telenursing practice guidelines. Resources relative to digital health and nursing informatics exist, but variations between provinces were also noted. CONCLUSIONS: The use of telehealth and virtual care services is becoming mainstream in Canadian health care. Despite variations across jurisdictions, the existing nursing practice guidance resources for delivering telehealth and virtual care are substantial and can serve as a beginning step for developing a standardized set of practice requirements or competencies to inform nursing practice and the education of future nurses.
Subject(s)
COVID-19 , Telemedicine , Humans , Telemedicine/organization & administration , Canada , COVID-19/epidemiology , Pandemics , SARS-CoV-2ABSTRACT
This paper presents a novel information generation methodology to support safer cycling patterns in urban environments, leveraging for that Large Language Models (LLMs), AI-based agents, and open geospatial data. By processing multiple files containing previously computed urban risk levels and existing mobility infrastructure, which are generated by exploiting open data sources, our method exploits multi-layer data preprocessing procedures and prompt engineering to create easy-to-use, user-friendly assistive systems that are able to provide useful information concerning cycling safety. Through a well-defined processing pipeline based on Data Ingestion and Preparation, Agents Orchestration, and Decision Execution methodological steps, our method shows how to integrate open-source tools and datasets, ensuring reproducibility and accessibility for urban planners and cyclists. Moreover, an AI agent is also provided, which fully implements our method and acts as a proof-of-concept implementation. This paper demonstrates the effectiveness of our method in enhancing cycling safety and urban mobility planning.â¢A novel method that combines LLMs and AI agents is defined to enhance the processing of multi-domain open geospatial data, potentially promoting cycling safety.â¢It integrates urban risk data and cycling infrastructure for a more comprehensive understanding of cycling resources, which become accessible by textual or audio prompts.
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BACKGROUND: Clinical practice settings have increasingly become dependent on the use of digital or eHealth technologies such as electronic health records. It is vitally important to support nurses in adapting to digitalized health care systems; however, little is known about nursing graduates' experiences as they transition to the workplace. OBJECTIVE: This study aims to (1) describe newly qualified nurses' experiences with digital health in the workplace, and (2) identify strategies that could help support new graduates' transition and practice with digital health. METHODS: An exploratory descriptive qualitative design was used. A total of 14 nurses from Eastern and Western Canada participated in semistructured interviews and data were analyzed using inductive content analysis. RESULTS: Three themes were identified: (1) experiences before becoming a registered nurse, (2) experiences upon joining the workplace, and (3) suggestions for bridging the gap in transition to digital health practice. Findings revealed more similarities than differences between participants with respect to gaps in digital health education, technology-related challenges, and their influence on nursing practice. CONCLUSIONS: Digital health is the foundation of contemporary health care; therefore, comprehensive education during nursing school and throughout professional nursing practice, as well as organizational support and policy, are critical pillars. Health systems investing in digital health technologies must create supportive work environments for nurses to thrive in technologically rich environments and increase their capacity to deliver the digital health future.
Subject(s)
Nurses , Qualitative Research , Workplace , Humans , Canada , Workplace/psychology , Female , Nurses/psychology , Adult , Male , Attitude of Health Personnel , Interviews as Topic , Electronic Health Records , Digital HealthABSTRACT
BACKGROUND: As technology will continue to play a pivotal role in modern-day health care and given the potential impact on the nursing profession, it is vitally important to examine the types and features of digital health education in nursing so that graduates are better equipped with the necessary knowledge and skills needed to provide safe and quality nursing care and to keep abreast of the rapidly evolving technological revolution. OBJECTIVE: In this scoping review, we aimed to examine and report on available evidence about digital health education and training interventions for nursing students at the undergraduate and graduate levels. METHODS: This scoping review was conducted using the Joanna Briggs Institute methodological framework and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). A comprehensive search strategy was developed and applied to identified bibliographic databases including MEDLINE (Ovid; 1946 to present), Embase (Ovid; 1974 to present), CINAHL (EBSCOhost; 1936 to present), ERIC (EBSCOhost; 1966 to present), Education Research Complete (EBSCOhost; inception to present), and Scopus (1976 to present). The initial search was conducted on March 3, 2022, and updated searches were completed on January 11, 2023, and October 31, 2023. For gray literature sources, the websites of select professional organizations were searched to identify relevant digital health educational programs or courses available to support the health workforce development. Two reviewers screened and undertook the data extraction process. The review included studies focused on the digital health education of students at the undergraduate or graduate levels or both in a nursing program. Studies that discussed instructional strategies, delivery processes, pedagogical theory and frameworks, and evaluation strategies for digital health education; applied quantitative, qualitative, and mixed methods; and were descriptive or discussion papers, with the exception of review studies, were included. Opinion pieces, editorials, and conference proceedings were excluded. RESULTS: A total of 100 records were included in this review. Of these, 94 records were identified from database searches, and 6 sources were identified from the gray literature. Despite improvements, there are significant gaps and limitations in the scope of digital health education at the undergraduate and graduate levels, consequently posing challenges for nursing students to develop competencies needed in modern-day nursing practice. CONCLUSIONS: There is an urgent need to expand the understanding of digital health in the context of nursing education and practice and to better articulate its scope in nursing curricula and enforce its application across professional nursing practice roles at all levels and career trajectories. Further research is also needed to examine the impact of digital health education on improving patient outcomes, the quality of nursing care, and professional nursing role advancement. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.11124/JBIES-22-00266.
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Education, Nursing, Graduate , Students, Nursing , Humans , Students, Nursing/statistics & numerical data , Education, Nursing, Graduate/methods , Education, Nursing, Baccalaureate/methodsABSTRACT
The advent of targeted therapies revolutionized treatments of advanced oncogene-driven non-small cell lung cancer (NSCLC). Nonetheless, despite initial dramatic responses, development of drug resistance is inevitable. Although mechanisms underlying acquired resistance, such as on-target mutations, bypass pathways, or lineage transformation, have been described, overcoming drug resistance remains challenging. Recent evidence suggests that drug-tolerant persister (DTP) cells, which are tumor cells tolerant to initial drug exposure, give rise to cells that acquire drug resistance. Thus, the possibility of eradicating cancer by targeting DTP cells is under investigation, and various strategies are proposed. Here, we review overall features of DTP cells, current efforts to define DTP markers, and potential therapeutic strategies to target and eradicate DTP cells in oncogene-driven NSCLC. We also discuss future challenges in the field.
Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Drug Resistance, Neoplasm , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Drug Resistance, Neoplasm/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Molecular Targeted Therapy , Animals , Drug Tolerance , Biomarkers, Tumor/genetics , MutationABSTRACT
Trade-offs resulting from the high demand of offspring production are a central focus of many subdisciplines within the field of biology. Yet, despite the historical and current interest on this topic, large gaps in our understanding of whole-organism trade-offs that occur in reproducing individuals remain, particularly as it relates to the nuances associated with female reproduction. This volume of Integrative and Comparative Biology (ICB) contains a series of papers that focus on reviewing trade-offs from the female-centered perspective of biology (i.e., a perspective that places female reproductive biology at the center of the topic being investigated or discussed). These papers represent some of the work showcased during our symposium held at the 2024 meeting of the Society for Integrative and Comparative Biology (SICB) in Seattle, Washington. In this roundtable discussion, we use a question-and-answer format to capture the diverse perspectives and voices involved in our symposium. We hope that the dialogue featured in this discussion will be used to motivate researchers interested in understanding trade-offs in reproducing females and provide guidance on future research endeavors.
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The broad range of disease aggressiveness together with imperfect screening, diagnostic, and treatment options in prostate cancer (PCa) makes medical decision-making complex. The primary goal of a multidisciplinary conference is to improve patient outcomes by combining evidence-based data and expert opinion to discuss optimal management, including for those patients with challenging presentations. The primary purpose of the genitourinary imaging specialist in the prostate cancer multidisciplinary conference is to use imaging findings to reduce uncertainty by answering clinical questions. In this review, we discuss the role and the opportunities for an imaging specialist to add value in the care of men with prostate cancer discussed at multidisciplinary conferences.
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Prostate cancer (PCa) remains the leading malignancy affecting men, with over 3 million men living with the disease in the US, and an estimated 288,000 new cases and almost 35,000 deaths in 2023 in the United States alone. Over the last few decades, imaging has been a cornerstone in PCa care, with a crucial role in the detection, staging, and assessment of PCa recurrence or by guiding diagnostic or therapeutic interventions. To improve diagnostic accuracy and outcomes in PCa care, remarkable advancements have been made to different imaging modalities in recent years. This paper focuses on reviewing the main innovations in the field of PCa magnetic resonance imaging, including MRI protocols, MRI-guided procedural interventions, artificial intelligence algorithms and positron emission tomography, which may impact PCa care in the future.
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BACKGROUND: Anxiety is a common and disabling condition that significantly impacts quality of life. Subsyndromal anxiety (SSA) refers to anxiety symptoms that do not meet the full diagnostic criteria for an anxiety disorder but pose a risk for developing such disorders. We aimed to provide practical recommendations for the treatment of SSA in primary care settings. METHODS: A narrative review was conducted to identify strategies for recognizing and treating patients with SSA. RESULTS: The recommendations for treating SSA include lifestyle modifications such as exercise and stress reduction techniques, psychotherapy, and pharmacological treatments, including natural compounds like the lavender oil extract Silexan. Regular follow-up care is essential to monitor treatment response and address ongoing symptoms. Additionally, the use of the GAD-7 tool is recommended for accurately identifying patients with SSA. CONCLUSION: Implementing these recommendations in primary care can lead to effective treatment of SSA, preventing the development of more severe anxiety disorders. An integrative approach, combining lifestyle modifications, psychotherapy, and pharmacotherapy, including natural compounds, offers significant benefits for managing anxiety.
Anxiety is prevalent and disablingSubsyndromal anxiety is a risk factor for anxiety disordersSubsyndromal anxiety can be assessed with the GAD-7 (Generalised Anxiety Disorder-7 scale)Subsyndromal anxiety can be treated with life-style modification, psychotherapy and pharmacological treatment, including silexan, a natural compound.
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Data on routine childhood vaccination coverage can only tell us who is under-vaccinated; it cannot explain why vaccine coverage is low. Collecting data on the reasons behind under-vaccination is necessary to implement cost-effective strategies that address key barriers and target interventions appropriately. However, no instruments that measure both vaccine acceptance and access factors among parents of children <5 y have been validated in high-income countries. This study aims to develop and validate the Vaccine Barriers Assessment Tool (VBAT) for Australia. We applied three phases of mixed methods data collection and analysis. In Phase 1, we developed a comprehensive list of 80 items reflecting all potential parental barriers to childhood vaccination, derived from published literature and behavioral theory. Through cognitive interviews (n = 28), we refined this list to 45 items. In Phase 2, we conducted a two-wave online survey to test the reliability and validity of these items in an Australian sample of parents (n = 532) with structural equation modeling, further refining the list to 35 items. In Phase 3, we conducted a final parent survey (n = 156), administering these items along with the Parent Attitudes toward Childhood Vaccination (PACV) scale for comparison. We reviewed participants' immunization register data to assess the predictive validity of the proposed models. The final 6-item short form and 15-item long form Vaccine Barriers Assessment Tool assess access, communal benefit, personal risk, equity, commitment, social norms, and trust in health-care workers. It is being applied for national surveillance in Australia and will be adapted for additional populations and vaccines.
Subject(s)
Parents , Vaccination , Humans , Australia , Parents/psychology , Female , Infant , Child, Preschool , Male , Vaccination/psychology , Vaccination/statistics & numerical data , Surveys and Questionnaires , Adult , Vaccination Coverage/statistics & numerical data , Reproducibility of Results , Vaccination Hesitancy/statistics & numerical data , Vaccination Hesitancy/psychology , Health Knowledge, Attitudes, Practice , Patient Acceptance of Health Care/statistics & numerical data , Patient Acceptance of Health Care/psychology , Vaccines/administration & dosageABSTRACT
OBJECTIVE: Clinical fear of cancer recurrence (FCR) was recently defined by a group of experts during a Delphi study. Five criteria were agreed upon, namely: (a) high levels of preoccupation, (b) high levels of worry, (c) that are persistent, (d) hypervigilance and hypersensitivity to physical sensations that e) may result in functional impairment. No existing instruments comprehensively capture all these criteria for clinical FCR. METHODS: To remedy this gap, a set of three patient-reported outcome instruments including a one-item screener, self-report questionnaire, and semi-structured clinical interview, named the Ottawa Clinical Fear of Recurrence instruments, were developed. To do so, the research team first conducted a literature review of potential items. Additional FCR experts discussed the content of the screener and interview. The self-report's items were assessed for content validity by the same expert panel using Likert ratings and the Content Validity Index to narrow down the number of items. The three instruments were piloted with a group of cancer survivors to assess face validity following the European Organization for Research and Treatment of Cancer recommendations. RESULTS: The literature review and content validity assessment led to a final draft pre-pilot of 23 potential items for the self-report questionnaire. The instruments were piloted. Pilot study participants suggested changing wording and response options (particularly for the self-report) for greater clarity. CONCLUSIONS: Based on the feedback received, minor modifications were made, mostly for the self-report. In general, content and face validity for the three instruments were good for both experts and cancer survivors.
Subject(s)
Fear , Neoplasm Recurrence, Local , Self Report , Humans , Fear/psychology , Surveys and Questionnaires/standards , Female , Reproducibility of Results , Neoplasm Recurrence, Local/psychology , Middle Aged , Male , Psychometrics/instrumentation , Adult , Cancer Survivors/psychology , Aged , Pilot Projects , Interviews as Topic , Neoplasms/psychology , Patient Reported Outcome Measures , Anxiety/psychologyABSTRACT
Despite elite human free divers achieving incredible feats in competitive free diving, there has yet to be a study that compares consummate divers, (i.e. northern elephant seals) to highly conditioned free divers (i.e., elite competitive free-diving humans). Herein, we compare these two diving models and suggest that hematological traits detected in seals reflect species-specific specializations, while hematological traits shared between the two species are fundamental mammalian characteristics. Arterial blood samples were analyzed in elite human free divers (n = 14) during a single, maximal volitional apnea and in juvenile northern elephant seals (n = 3) during rest-associated apnea. Humans and elephant seals had comparable apnea durations (â¼6.5 min) and end-apneic arterial Po2 [humans: 40.4 ± 3.0 mmHg (means ± SE); seals: 27.1 ± 5.9 mmHg; P = 0.2]. Despite similar increases in arterial Pco2 (humans: 33 ± 5%; seals: 16.3 ± 5%; P = 0.2), only humans experienced reductions in pH from baseline (humans: 7.45 ± 0.01; seals: 7.39 ± 0.02) to end apnea (humans: 7.37 ± 0.01; seals: 7.38 ± 0.02; P < 0.0001). Hemoglobin P50 was greater in humans compared to elephant seals (29.9 ± 1.5 and 28.7 ± 0.6 mmHg, respectively; P = 0.046). Elephant seals overall had higher carboxyhemoglobin (COHb) levels (5.9 ± 2.6%) compared to humans (0.8 ± 1.2%; P < 0.0001); however, following apnea, COHb was reduced in seals (baseline: 6.1 ± 0.3%; end apnea: 5.6 ± 0.3%) and was slightly elevated in humans (baseline: 0.7 ± 0.1%; end apnea: 0.9 ± 0.1%; P < 0.0002, both comparisons). Our data indicate that during static apnea, seals have reduced hemoglobin P50, greater pH buffering, and increased COHb levels. The differences in hemoglobin P50 are likely due to the differences in the physiological environment between the two species during apnea, whereas enhanced pH buffering and higher COHb may represent traits selected for in elephant seals.NEW & NOTEWORTHY This study uses similar methods and protocols in elite human free divers and northern elephant seals. Using highly conditioned divers (elite free-diving humans) and highly adapted divers (northern elephant seals), we explored which hematological traits are fundamentally mammalian and which may have been selected for. We found differences in P50, which may be due to different physiological environments between species, while elevated pH buffering and carbon monoxide levels might have been selected for in seals.
Subject(s)
Apnea , Diving , Seals, Earless , Animals , Seals, Earless/blood , Humans , Diving/physiology , Apnea/blood , Apnea/physiopathology , Male , Adult , Female , Species Specificity , Hemoglobins/metabolism , Young Adult , Carbon Dioxide/blood , Oxygen/bloodABSTRACT
OBJECTIVE: To determine the prevalence of anterior uveitis in dogs and cats hospitalized with a diagnosis of systemic inflammatory response syndrome (SIRS). ANIMALS STUDIED: Dogs and cats hospitalized between May 2020 and January 2021 were prospectively included. PROCEDURES: Patients were categorized into two different groups: The first group included patients diagnosed with SIRS, and the second group included patients hospitalized without SIRS as a control group. Daily physical and ophthalmological examinations were conducted during hospitalization. Diagnosis of anterior uveitis was made based on the presence of aqueous flare, low intraocular pressure, and other associated ocular signs such as episcleral injection and miosis. A multinomial logistic regression analysis was conducted to investigate factors associated with SIRS and anterior uveitis development. RESULTS: The study comprised 42 patients with SIRS and 26 patients without SIRS. Among those with SIRS, 38% developed anterior uveitis, whereas only 7.7% of patients without SIRS showed signs of anterior uveitis. The prevalence of uveitis was significantly higher in animals with SIRS compared to those without SIRS (p < .05). CONCLUSION: Anterior uveitis is more prevalent in patients with SIRS than patients without SIRS. Therefore, complete ophthalmic examination is recommended in all patients presenting with this syndrome.
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Urban areas are undergoing significant changes with the rise of smart cities, with technology transforming how cities develop through enhanced connectivity and data-driven services. However, these advancements also bring new challenges, especially in dealing with urban emergencies that can disrupt city life and infrastructure. The emergency management systems have become crucial elements for enabling cities to better handle urban emergencies, although ensuring the reliability and detectability of such system remains critical. This article introduces a new method to perform reliability and detectability assessments. By using Fault Tree Markov chain models, this article evaluates their performance under extreme conditions, providing valuable insights for designing and operating urban emergency systems. These analyses fill a gap in the existing research, offering a comprehensive understanding of emergency management systems functionality in complex urban settings.
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INTRODUCTION: Expert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. METHODS: We conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. RESULTS: Individual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. CONCLUSION: While the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.
Subject(s)
Obsessive-Compulsive Disorder , Outcome Assessment, Health Care , Humans , Obsessive-Compulsive Disorder/therapy , Obsessive-Compulsive Disorder/drug therapy , Obsessive-Compulsive Disorder/diagnosis , Adult , Randomized Controlled Trials as Topic , Remission InductionABSTRACT
Purpose: To evaluate effects of aerobic and resistance exercises for cancer-related pain in adults with and surviving cancer. Secondary objectives were to a) evaluate the effect of exercise on fatigue, psychological function, physical function, b) assess fidelity to exercise. Design: A systematic search of MEDLINE, EMBASE, AMED, CINAHL and Cochrane Central Register of Controlled Trials was conducted to identify randomised controlled trials (RCTs) comparing aerobic and/or resistance exercise to control groups. The primary endpoint were changes in cancer-related pain intensity from baseline to post intervention. Meta-regression analysis evaluated predictors for heterogeneity between study findings. Tolerability was defined as reporting of exercise-induced adverse events while fidelity evaluated by reported intervention dropout. Results: Twenty-three RCTs including 1954 patients (age 58 ± 8.5 years; 78 % women); 1087 (56 %) and 867 (44 %) allocated to aerobic/resistance exercise therapy and control group, respectively. Exercise therapy was associated with small to moderate decreases in cancer-related pain compared to controls (SMD = 0.38, 95 % CI: 0.17, 0.58). Although there was significant heterogeneity between individual and pooled study effects (Q = 205.25, p < 0.0001), there was no publication bias. Meta-regression including supervision, age, duration and exercise type as moderators showed no significant differences in reported outcomes. Analysis of secondary outcomes revealed a moderate effect for improvements in physical function, fatigue and psychological symptoms. Conclusions: Aerobic and resistance exercises are tolerable and effective adjunct therapies to reduce cancer-related pain while also improving physical function, fatigue and mood. Future RCTs of dose, frequency, compliance and exercise type in specific cancer settings are required.
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INTRODUCTION: A variety of procedures for the endoscopic surgical treatment of symptomatic benign prostatic hyperplasia (BPH) refractory to medical therapy have existed for decades. The present study examined trends in surgeon compensation for these treatments within Canada. METHODS: The physician fee schedule for BPH surgery across 10 Canadian provinces for the years 2010 and 2023 were obtained. A descriptive study examined first the provincial reimbursement for transurethral resection of prostate (TURP) and laser ablative/enucleation surgery; second, the difference in TURP reimbursement between 2010 and 2023; and third, the annual change in TURP reimbursement juxtaposed with the annual change in the provincial Consumer Price Index (CPI) and annual salary for the working population aged 35-44. RESULTS: Seven of 10 Canadian provinces reimburse laser BPH surgery equally to TURP. The average provincial TURP reimbursement is $545, ranging from $451 in Ontario to $688 in Saskatchewan. Since 2010, TURP reimbursement has varied by province from a 0% net change in Ontario to an increase of 21% in Nova Scotia. Reimbursement for TURP has increased at a slower pace than the local CPI, and for half of the provinces at a slower pace than the annual salary for people aged 35-44. CONCLUSIONS: The compensation model for endoscopic BPH surgery does not have a unified structure in Canada that is consistent across provinces, nor does it keep up with inflation, possibly impacting future recruitment, increasing geographic disparities, and most importantly, limiting the adoption of new BPH therapies.
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Many animals and plants have species-typical annual cycles, but individuals vary in their timing of life-history events. Individual variation in fur replacement (moult) timing is poorly understood in mammals due to the challenge of repeated observations and longitudinal sampling. We examined factors that influence variation in moult duration and timing among elephant seals (Mirounga angustirostris). We quantified the onset and progression of fur loss in 1178 individuals. We found that an exceptionally rapid visible moult (7 days, the shortest of any mammals or birds), and a wide range of moult start dates (spanning 6-10× the event duration) facilitated high asynchrony across individuals (only 20% of individuals in the population moulting at the same time). Some of the variation was due to reproductive state, as reproductively mature females that skipped a breeding season moulted a week earlier than reproductive females. Moreover, individual variation in timing and duration within age-sex categories far outweighed (76-80%) variation among age-sex categories. Individuals arriving at the end of the moult season spent 50% less time on the beach, which allowed them to catch up in their annual cycles and reduce population-level variance during breeding. These findings underscore the importance of individual variation in annual cycles.