Immediate Breast Reconstruction Outcomes in Patients with Prior Mantle and Whole Breast Irradiation.

Background: Limited studies have detailed the risk of mastectomy with immediate breast reconstruction among women who previously received mantle field radiation. Methods: A single institution retrospective review from 2010 to 2020 of patients previously treated with mantle field radiation (MF-RT) and subsequent mastectomy with immediate breast reconstruction was performed. Patients with prior whole breast irradiation (WBI) were also included as a reference group. Demographic, comorbidity, and surgical factors were collected. The primary outcome was major complications, defined as those requiring reoperation, intravenous antibiotics, or debridement. Results: Fourteen patients with prior MF-RT (27 breasts) and 129 with prior WBI (132 breasts) underwent mastectomy with immediate reconstruction. Prior MF-RT patients were significantly younger (43.8 versus 57.5, P < 0.001) and had significantly lower body mass index (23.6 versus 26.8, P = 0.004) compared with prior WBI patients. Nipple-sparing mastectomy was significantly more common in the mantle than in the WBI patients (78.6% versus 35.9%, P = 0.03). Most (13, 92.9%) prior mantle patients underwent tissue expander/implant-based reconstruction. Three (21.4%) prior MF-RT patients had major complications at any point, but none required an alternative type of reconstruction. On multiple variable analysis, there was no significant difference in major complication risk among prior MF-RT versus WBI patients (HR 0.74, confidence interval 0.20-2.70, P = 0.74). Conclusion: Immediate tissue expander/implant-based reconstruction in prior MF-RT patients seems safe, with a complication risk similar to that of prior WBI patients.

Rapid normalization of vitamin D deficiency in PICU (VITdALIZE-KIDS): study protocol for a phase III, multicenter randomized controlled trial.

BACKGROUND: The rate of vitamin D deficiency (VDD) in critically ill children worldwide has been estimated at 50%. These children are at risk of multiple organ dysfunction, chronic morbidity, and decreased health related quality of life (HRQL). Pediatric and adult ICU clinical trials suggest that VDD is associated with worse clinical outcomes, although data from supplementation trials are limited and inconclusive. Our group's phase II multicenter dose evaluation pilot study established the efficacy and safety of an enteral weight-based cholecalciferol loading dose to rapidly restore vitamin D levels in critically ill children. METHODS: Our aim is to evaluate the impact of this dosing regimen on clinical outcomes. VITdALIZE-KIDS is a pragmatic, phase III, multicenter, double-blind RCT aiming to randomize 766 critically ill children from Canadian PICUs. Participants are randomized using a 1:1 scheme to receive a single dose at enrollment of enteral cholecalciferol (10,000 IU/kg, max 400,000 IU) or placebo. Eligibility criteria include critically ill children aged newborn (> 37 weeks corrected gestational age) to < 18 years who have blood total 25-hydroxyvitamin D < 50 nmol/L. The primary objective is to determine if rapid normalization of vitamin D status improves HRQL at 28 days following enrollment. The secondary objective is to evaluate the impact of rapid normalization of vitamin D status on multiple organ dysfunction. The study includes additional tertiary outcomes including functional status, HRQL and mortality at hospital discharge and 90 days, PICU and hospital length of stay, and adverse events related to vitamin D toxicity. Additionally, we are performing comprehensive vitamin D speciation and non-targeted metabolite profiling as part of a sub-study for the first 100 participants from whom an enrollment and at least one post-intervention blood and urine sample were obtained. DISCUSSION: The VITdALIZE-KIDS trial is the first phase III, multicenter trial to evaluate whether rapid normalization of vitamin D status could represent a simple, inexpensive, and safe means of improving outcomes following pediatric critical illness. Recruitment was initiated in June 2019 and is expected to continue to March 2026. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03742505. Study first submitted on November 12, 2018 https://clinicaltrials.gov/study/NCT03742505.

Dose de-intensified 3-day photon, proton, or brachytherapy: a nonrandomized controlled partial breast irradiation trial.

BACKGROUND: The optimal approach for partial breast irradiation (PBI) is unknown. We investigated a novel de-intensified 3-fraction PBI regimen for photons, protons, and brachytherapy. METHODS: A multicenter nonrandomized controlled trial with primary outcome of adverse cosmesis at 3 years versus pre-PBI. Eligibility criteria were ≥ age 50 years treated with breast-conserving surgery for node-negative estrogen receptor positive (ER+) invasive breast cancer or any ductal carcinoma in-situ (DCIS) measuring ≤ 2.5 cm. Photon and proton PBI were prescribed 21.9 Gy (RBE) and brachytherapy 21 Gy in 3 fractions. Radiotherapy technique and use of adjuvant endocrine therapy was selected at physician and patient discretion. RESULTS: Between June 17, 2015 and July 13, 2017, 161 eligible patients were treated with photons (56), protons (49), or brachytherapy (56). Median patient age was 66.8 years. 126 (78.3%) had invasive breast cancer (all ER+) and 35 (21.7%) had DCIS (88.6% ER+). 54.0% of patients with invasive breast cancer and 25.8% of patients with ER+ DCIS initiated and adhered to prescribed endocrine therapy. The proportion of patients with adverse cosmesis (by trained nurse assessment) was 14.5% at baseline, 2.3% at 3 years (difference -12.2%, 95% CI (-100%, -6.4%)). Adverse cosmesis at last-follow-up, with median follow-up 5 years, was 5.7% by nurse assessment, 5.6% by panel assessment of digital photographs, and 5.2% by patient self-report. There were no observed clinically meaningful changes in other patient reported outcomes, and just two grade 2 or higher adverse events, both grade 2, in the brachytherapy cohort. 5-year local recurrence-free and progression-free survival were 98.0% and 95.5%, respectively. There were no local recurrences amongst 60 patients with invasive breast cancer and Ki67 ≤ 13.25%. CONCLUSIONS: De-intensified 3-day PBI provided favorable disease control, tolerability, and cosmetic outcomes, meeting the pre-specified criteria for acceptability. This approach is an attractive option for small node-negative ER+ BC and DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02453737.

Family Medicine Resident Scholarly Activity Infrastructure, Output, and Dissemination: A CERA Survey.

PURPOSE: Meeting scholarly activity requirements continues to be a challenge in many family medicine (FM) residency programs. Studies comprehensively describing FM resident scholarship have been limited. We sought to identify institutional factors associated with increased scholarly output and meeting requirements of the Accreditation Council for Graduate Medical Education (ACGME). OBJECTIVES: Our goals were to: (1) describe scholarly activity experiences among FM residents compared with ACGME requirements; (2) classify experiences by Boyer's domains of scholarship; and (3) associate experiences with residency program characteristics and scholarly activity infrastructure. METHODS: This was a cross-sectional survey. The survey questions were part of an omnibus survey to FM residency program directors conducted by the Council of Academic Family Medicine Educational Research Alliance (CERA). All ACGME-accredited US FM residency program directors, identified by the Association of Family Medicine Residency Directors, were sampled. RESULTS: Of the 691 eligible program directors, 298 (43%) completed the survey. The respondents reported that 25% or more residents exceeded ACGME minimum output, 17% reported that 25% or more residents published their work, and 50% reported that 25% or more residents delivered conference presentations. Programs exceeding ACGME scholarship requirements exhibit robust infrastructure characterized by access to faculty mentorship, scholarly activity curricula, Institutional Review Board, medical librarian, and statistician. CONCLUSIONS: These findings suggest the need for codified ACGME requirements for scholarly activity infrastructure to ensure access to resources in FM residency programs. By fostering FM resident engagement in scholarly activity, programs help to create a culture of inquiry, and address discrepancies in funding and output among FM residency programs.

Addressing immortal time bias in precision medicine: Practical guidance and methods development.

OBJECTIVE: To compare theoretical strengths and limitations of common immortal time adjustment methods, propose a new approach using multiple imputation (MI), and provide practical guidance for using MI in precision medicine evaluations centered on a real-world case study. STUDY SETTING AND DESIGN: Methods comparison, guidance, and real-world case study based on previous literature. We compared landmark analysis, time-distribution matching, time-dependent analysis, and our proposed MI application. Guidance for MI spanned (1) selecting the imputation method; (2) specifying and applying the imputation model; and (3) conducting comparative analysis and pooling estimates. Our case study used a matched cohort design to evaluate overall survival benefits of whole-genome and transcriptome analysis, a precision medicine technology, compared to usual care for advanced cancers, and applied both time-distribution matching and MI. Bootstrap simulation characterized imputation sensitivity to varying data missingness and sample sizes. DATA SOURCES AND ANALYTIC SAMPLE: Case study used population-based administrative data and single-arm precision medicine program data from British Columbia, Canada for the study period 2012 to 2015. PRINCIPAL FINDINGS: While each method described can reduce immortal time bias, MI offers theoretical advantages. Compared to alternative approaches, MI minimizes information loss and better characterizes statistical uncertainty about the true length of the immortal time period, avoiding false precision. Additionally, MI explicitly considers the impacts of patient characteristics on immortal time distributions, with inclusion criteria and follow-up period definitions that do not inadvertently risk biasing evaluations. In the real-world case study, survival analysis results did not substantively differ across MI and time distribution matching, but standard errors based on MI were higher for all point estimates. Mean imputed immortal time was stable across simulations. CONCLUSIONS: Precision medicine evaluations must employ immortal time adjustment methods for unbiased, decision-grade real-world evidence generation. MI is a promising solution to the challenge of immortal time bias.

Review of skin grafting in equine wounds: indications and techniques.

Skin grafting is a simple technique that can be performed by equine practitioners to improve cosmetic outcomes in wounds with large skin defects that would not heal functionally or cosmetically with standard wound therapy interventions. Successful skin grafting is not difficult but relies upon appropriate preparation of the wound bed and effective immobilisation of the grafted area after skin graft placement. Prior to grafting, the wound bed should be treated with a moist wound healing dressing to prepare the granulation tissue bed to receive the graft. For best results, skin grafts should be placed in wounds free of infection with healthy granulation tissue, and motion should be reduced in the graft region in the early postoperative period. When successful, skin grafts cover granulation tissue and encourage wound contraction and epithelialisation while decreasing exuberant granulation tissue resulting in a more cosmetic result. This review will advance practitioners' understanding of skin grafting in horses, including graft classification and techniques, donor site selection, recipient site preparation, postoperative management strategies to optimise graft retention and ongoing research in this field.

Characterizing fluvial impact on the biochemical composition of particulate organic matter in the Laptev Sea and Western East Siberian Sea during the late summer of 2018.

The Laptev Sea (LS) and Western East Siberian Sea (W-ESS) are paradigmatic examples of seas dominated by terrestrial organic matter, attributed to substantial Siberian River discharges and coastal erosion. The influx of terrestrial organic matter significantly alters the biochemical composition of particulate organic matter (POM) in these Arctic coastal regions, potentially reducing the nutritional quality available to higher trophic levels. This study investigated the origin and qualitative characteristics of POM in the LS and W-ESS during the late summer of 2018 by analyzing elemental ratios (C/N ratio), stable carbon isotopes (δ13C), and biochemical compositions (biomolecular and amino acid (AA) compositions). The conspicuously depleted δ13C values (mean ± standard deviation (SD) = -30.2 ± 0.5 ‰) and alongside elevated molar C/N ratios (mean ± SD = 18.1 ± 6.2) suggest that terrestrial organic matter is the predominant source of POM in the study area. Although carbohydrates (CHO) were the dominant biomolecules, their prevalence was higher in the river-influenced W-ESS region (67.7 ± 6.6 %) than in the LS region (58.6 ± 13.9 %; p < 0.05). Furthermore, the CHO composition was closely associated with freshwater content and river fraction, suggesting that the heightened contribution of CHO may stem from terrestrial organic matter delivered by river inputs. Lower concentrations of particulate hydrolyzable AA (PAA) and carbon and nitrogen normalized yields of AAs (AA-POC% and AA-PON%) along with reduced contribution of glycine suggested a substantial contribution of terrestrial POM to both LS and W-ESS POM. Overall, this study provides valuable insights into the terrestrial influence on POM composition in Arctic marine ecosystems, emphasizing the need for continued monitoring of the consequences of terrestrial carbon inputs in the changing Arctic environment.

Determining the N-Glycan and Collagen/Extracellular Matrix Protein Compositions in a Novel Outcome Cohort of Prostate Cancer Tissue Microarrays Using MALDI-MSI.

Prostate cancer is a significant health concern, with metastasis posing major clinical challenges and resulting in poor patient outcome. Despite screening and treatment advances, a critical need for novel biomarkers to predict prostate cancer progression at the time of prostatectomy persists. Here, we assessed aberrant N-glycosylation patterns and alterations in extracellular matrix proteins as potential biomarkers of predicting prostate cancer severity in a unique patient outcome cohort. Tissue microarray slides were assembled from primary prostatectomy specimens that were categorized into "no evidence of disease (NED)" and "metastasis (MET)" designations based on >5-year disease progression outcomes. Serial mass spectrometry imaging techniques were performed to analyze N-glycans and extracellular matrix (ECM) components in formalin-fixed paraffin-embedded cores. The results revealed a significant upregulation of bisecting and multi-antennary core fucosylated N-glycans in MET tissues when compared to NED tissues. Alterations in ECM composition in both NED and MET cohorts were observed, particularly in collagen species and the amount of hydroxyproline content. Results suggest a coordinated alteration of ECM protein and glycosylation content in prostate cancer tissues can be predictive for post-prostatectomy disease progression.

A gut microbiota rheostat forecasts responsiveness to PD-L1 and VEGF blockade in mesothelioma.

Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive. Here, we report the outcomes of a multi-centre phase II clinical trial (MiST4, NCT03654833) evaluating atezolizumab and bevacizumab (AtzBev) in patients with relapsed mesothelioma. We also use tumour tissue and gut microbiome sequencing, as well as tumour spatial immunophenotyping to identify factors associated with treatment response. MIST4 met its primary endpoint with 50% 12-week disease control, and the treatment was tolerable. Aneuploidy, notably uniparental disomy (UPD), homologous recombination deficiency (HRD), epithelial-mesenchymal transition and inflammation with CD68+ monocytes were identified as tumour-intrinsic resistance factors. The log-ratio of gut-resident microbial genera positively correlated with radiological response to AtzBev and CD8+ T cell infiltration, but was inversely correlated with UPD, HRD and tumour infiltration by CD68+ monocytes. In summary, a model is proposed in which both intrinsic and extrinsic determinants in mesothelioma cooperate to modify the tumour microenvironment and confer clinical sensitivity to AtzBev. Gut microbiota represent a potentially modifiable factor with potential to improve immunotherapy outcomes for individuals with this cancer of unmet need.

"I Just Assumed This Was Already Being Done": Canadian Patient Preferences for Enhanced Data Sharing for Precision Oncology.

PURPOSE: In Canada, health data are siloed, slowing bioinnovation and evidence generation for personalized cancer care. Secured data-sharing platforms (SDSPs) can enable data analysis across silos through rapid concatenation across trial and real-world settings and timely researcher access. To motivate patient participation and trust in research, it is critical to ensure that SDSP design and oversight align with patients' values and address their concerns. We sought to qualitatively characterize patient preferences for the design of a pan-Canadian SDSP. METHODS: Between January 2022 and July 2023, we conducted pan-Canadian virtual focus groups with individuals who had a personal history of cancer. Following each focus group, participants were invited to provide feedback on early-phase analysis results via a member-checking survey. Three trained qualitative researchers analyzed data using thematic analysis. RESULTS: Twenty-eight individuals participated across five focus groups. Four focus groups were conducted in English and one in French. Thematic analysis generated two major and five minor themes. Analytic themes spanned personal and population implications of data sharing and willingness to manage perceived risks. Participants were supportive of increasing access to health data for precision oncology research, while voicing concerns about unintended data use, reidentification, and inequitable access to costly therapeutics. To mitigate perceived risks, participants highlighted the value of data access oversight and governance and informational transparency. CONCLUSION: Strategies for secured data sharing should anticipate and mitigate the risks that patients perceive. Participants supported enhancing timely research capability while ensuring safeguards to protect patient autonomy and privacy. Our study informs the development of data-governance and data-sharing frameworks that integrate real-world and trial data, informed by evidence from direct patient input.

Upgrading of Grade Group 1 Prostate Cancer at Prostatectomy: Germline Risk Factors in a Prospective Cohort.

BACKGROUND: Localized prostate tumors show significant spatial heterogeneity, with regions of high-grade disease adjacent to lower-grade disease. Consequently, prostate cancer biopsies are prone to sampling bias, potentially leading to underestimation of tumor grade. To study the clinical, epidemiologic and molecular hallmarks of this phenomenon, we conducted a prospective study of grade upgrading: differences in detected prostate cancer grade between biopsy and surgery. METHODS: We established a prospective, multi-institutional cohort of men with Grade Group 1 (GG1) prostate cancer on biopsy who underwent radical prostatectomy. Upgrading was defined as detection of GG2+ in the resected tumor. Germline DNA from 192 subjects was subjected to whole-genome sequencing to quantify ancestry, pathogenic variants in DNA damage response genes and polygenic risk. RESULTS: Of 285 men, 67% upgraded at surgery. PSA density and percent of cancer in pre-prostatectomy positive biopsy cores were significantly associated with upgrading. No assessed genetic risk factor was predictive of upgrading, including polygenic risk scores for prostate cancer diagnosis. CONCLUSIONS: In a cohort of low-grade prostate cancer patients, a majority upgraded at radical prostatectomy. PSA density and percent of cancer in pre-prostatectomy positive biopsy cores portended the presence of higher-grade disease, while germline genetics was not informative in this setting. Patients with low-risk prostate cancer, but elevated PSA density or percent cancer in positive biopsy cores, may benefit from repeat biopsy, additional imaging or other approaches to complement active surveillance. IMPACT: Further risk stratification of patients with low-risk prostate cancer may provide useful context for active surveillance decision-making.

Small towns limit dispersal and reduce genetic diversity in populations of Texas horned lizards.

There is a general expectation that urban populations will be fragmented and the movement of individuals will be restricted leading to low effective population sizes, low genetic diversity, higher inbreeding, and higher differentiation than populations living in more continuous habitat. In this study, we compare the genetic diversity and differentiation of Texas horned lizards that are found in four small towns (Kenedy, Karnes City, Rockdale, and Smithville) in Texas and at Tinker Air Force Base, Oklahoma to populations that occur in 16 natural areas and to an introduced population in South Carolina. We also present more detailed spatial genetic data and home range data for several of the towns. Texas horned lizards (Phrynosoma cornutum) living in small towns have lower genetic diversity, higher differentiation, and smaller effective population sizes than populations located in more natural areas. There was evidence for human-mediated movement of lizards into town; however, it has not been enough to counteract the effects of drift. Home range size is smaller in town than in more natural areas. Genetic patterns suggest dispersal occurs over short distances and is inhibited across areas with a high percent of impervious surface and major roads. These data suggest that effective planning to maintain suitable habitat and corridors to facilitate movement is critical to maintaining small terrestrial species like the Texas horned lizard and must be integrated into the early stages of urban development.

Clinical and Practice Innovation Improving the Practice of Family Medicine.

Quite a lineup showcasing JABFM's emphasis on research and information for family medicine to improve patients' lives. Articles cover many topics: telemedicine, a clinical decision support tool, control of cardiovascular risk factors, opioid dose reduction, cancer survivorship care, patient engagement with case management/navigation, primary care physician capacity and usual source of care, marketing practices of Medicare Advantage programs, review articles (new diabetes medicine and treatment CHF with reduced ejection fraction), and more.

Next-generation sequencing in oncology: challenges in economic evaluations.

INTRODUCTION: Next-generation sequencing (NGS) identifies genetic variants to inform personalized treatment plans. Insufficient evidence of cost-effectiveness impedes the integration of NGS into routine cancer care. The complexity of personalized treatment challenges conventional economic evaluation. Clearly delineating challenges informs future cost-effectiveness analyses to better value and contextualize health, preference-, and equity-based outcomes. AREAS COVERED: We conducted a scoping review to characterize the applied methods and outcomes of economic evaluations of NGS in oncology and identify existing challenges. We included 27 articles published since 2016 from a search of PubMed, Embase, and Web of Science. Identified challenges included defining the evaluative scope, managing evidentiary limitations including lack of causal evidence, incorporating preference-based utility, and assessing distributional and equity-based impacts. These challenges reflect the difficulty of generating high-quality clinical effectiveness and real-world evidence (RWE) for NGS-guided interventions. EXPERT OPINION: Adapting methodological approaches and developing life-cycle health technology assessment (HTA) guidance using RWE is crucial for implementing NGS in oncology. Healthcare systems, decision-makers, and HTA organizations are facing a pivotal opportunity to adapt to an evolving clinical paradigm and create innovative regulatory and reimbursement processes that will enable more sustainable, equitable, and patient-oriented healthcare.

Probability errors in children's judgements about the likelihood of social characteristics.

The studies reported here investigated mechanisms underlying children's tendency to commit the conjunction fallacy (judging that a conjunction of two events is more likely than one of the events in isolation) when judging people's characteristics. Study 1 investigated these errors in 4- and 5-year-olds (N = 58) using a newly developed social judgement task in which children judged whether a conjunction or one of its elements would apply to a protagonist. Children made conjunction fallacy errors at chance level. Study 2 (N = 71) replicated these findings using an adapted version of the task, in which children separately judged the likelihood of the conjunction and each of its events. Study 3 investigated age-related changes in conjunction fallacy errors in a sample of 148 children aged 4 to 11 years old and 130 adults. This study also investigated how providing background information on the protagonist influenced error rate. Unlike younger children, 10- and 11-year-olds committed the conjunction fallacy at chance level in the absence of background information, but providing information consistent with the likely component of the conjunction significantly increased their error rate. Adults' error rate also significantly increased after the introduction of background information. Across all three studies, conjunction fallacy errors were unrelated to cognitive and social-cognitive abilities, such as verbal ability, theory of mind, and inhibitory control (Studies 1 and 2), and prejudice and hindsight bias (Study 3). These findings suggest that it is only in the second decade of life that children use social information to inform their judgements about people and that social decision-making errors are not determined by core aspects of cognitive and social-cognitive development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Development of a Global Physical Literacy (GloPL) Action Framework: Study protocol for a consensus process.

BACKGROUND: The holistic concept of physical literacy (PL) has gained growing attention in recent research, policy, and practice. Many important policy documents of the physical activity and educational fields (e.g., Global Action Plan on Physical Activity 2018-2030 by the World Health Organization, UNESCO's Quality Physical Education guidelines for policymakers) have specified PL. However, a clear framework for action is needed, as most initiatives across the world are fragmented, lack a prospective orientation, can benefit from conceptual clarification, and are not linked to effective translation into practice. Therefore, we aim to consensually develop a Global Physical Literacy (GloPL) Action Framework to define goals and principles (asking what is needed) as well as actions and ways (asking how these can be achieved) to move PL forward. MATERIALS AND METHODS: We apply a three-stage group Delphi technique involving three representation groups: (a) geographical representatives to achieve global coverage of perspectives; (b) representatives of special thematic interest reflecting prominent gaps of current PL activities; and (c) representatives of societies from the broad field of physical activity and health to facilitate dissemination. The process will begin with an individual pre-Delphi exercise, in which experts generate initial ideas for the framework, followed by a four-eye document analysis to derive themes for the discussion. Subsequently, the experts will meet face-to-face in three online rounds to discuss and prioritize the themes. Interspersed formal voting with pre-defined agreement thresholds (via descriptive statistics) will inform the inclusion of themes within the final framework. CONCLUSIONS: A global consensus on goals, principles, actions, and ways for the development of PL has the potential to provide a largely accepted roadmap for future activities in research, policy, and practice. The co-production approach will help disseminate the GloPL Action Framework and benefit work in relevant application fields of physical activity and health worldwide.

Learning Networks: How Family Medicine Departments Are Meeting the Requirement.

BACKGROUND AND OBJECTIVES: In 2023, the Accreditation Council for Graduate Medical Education added participation within a "learning collaborative" or "learning network" (LN) as a requirement for family medicine residencies. The structure and scope of what makes an acceptable LN was only vaguely defined. The purpose of this study was to learn how many family medicine residencies associated with departments already belong to LNs, the purpose and funding of these existing LNs, and barriers to entering LNs. METHODS: An online survey was sent to family medicine department chairs through a Council of Academic Family Medicine Educational Research Alliance omnibus study from August to September 2023. Survey questions explored the purpose, structure, and funding of LNs that associated residency programs already belonged to as well as the chairs' beliefs and knowledge about LNs. RESULTS: Of the 227 chairs, 119 completed the survey (50.2%). About 53% reported that their department was part of an LN, with more than one-third belonging for 5 years or less; 47% had a low understanding of what an LN is; and 71% had little to no concern that collaborating in an LN would negatively affect residency recruitment. The purpose of most LNs was a mix of research, education, and clinical activities. Faculty's lack of knowledge about LNs and lack of time were the top barriers identified to joining an LN. Funding was varied, and departmental funding was positively associated with administrative control of the LN. CONCLUSIONS: About half of the residency programs associated with family medicine departments already belong to LNs. Wide variation among existing LNs may lead to significantly disparate outcomes for residents and residencies as they navigate this new requirement.

Planning for implementation success: insights from conducting an implementation needs assessment.

AIM: The aim of this paper is to provide insights into conducting an implementation needs assessment using a case example in a less-research-intensive setting. DESIGN AND METHODS: In the case example, an implementation needs assessment was conducted, including1 an environmental scan of the organization's website and preliminary discussions with key informants to learn about the implementation context, and2 a formal analysis of the evidence-practice gap (use of sedation interruptions) deploying a chart audit methodology using legal electronic reports. RESULTS: Our needs assessment was conducted over 5 months and demonstrated how environmental scans reveal valuable information that can inform the evidence-practice gap analysis. A well-designed gap analysis, using suitable indicators of best practice, can reveal compliance rates with local protocol recommendations, even with a small sample size. In our case, compliance with the prescribed practices for sedation interruptions ranged from 65% (n=53) to as high as 84% (n=69). CONCLUSIONS: Implementation needs assessments provide valuable information that can inform implementation planning. Such assessments should include an environmental scan to understand the local context and identify both current recommended best practices and local best practices for the intervention of interest. When addressing an evidence-practice gap, analyses should quantify the difference between local practice and desired best practice. IMPACT: The insights gained from the case example presented in this paper are likely transferrable to implementation research or studies conducted in similar, less-research-intensive settings. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A257.

Targeting DNA Damage Response Deficiency in Thoracic Cancers.

Thoracic cancers comprise non-small cell lung cancers (NSCLCs), small cell lung cancers (SCLCs) and malignant pleural mesotheliomas (MPM). Collectively, they account for the highest rate of death from malignancy worldwide. Genomic instability is a universal feature of cancer, which fuels mutations and tumour evolution. Deficiencies in DNA damage response (DDR) genes amplify genomic instability. Homologous recombination deficiency (HRD), resulting from BRCA1/BRCA2 inactivation, is exploited for therapeutic synthetic lethality with poly-ADP ribose polymerase (PARP) inhibitors in breast and ovarian cancers, as well as in prostate and pancreatic cancers. However, DDR deficiency and its therapeutic implications are less well established in thoracic cancers. Emerging evidence suggests that a subset of thoracic cancers may harbour DDR deficiency and may, thus, be effectively targeted with DDR agents. Here, we review the current evidence surrounding DDR in thoracic cancers and discuss the challenges and promise for achieving clinical benefit with such therapeutics.