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Background Disseminating care guidelines into clinical practice remains challenging, partly due to inadequate evidence on how best to help clinics incorporate new guidelines into routine care. This is particularly true in safety net community health centers (CHCs). Methods This pragmatic comparative effectiveness trial used a parallel mixed methods design. Twenty-nine CHC clinics were randomized to receive increasingly intensive implementation support (implementation toolkit (arm 1); toolkit + in-person training + training webinars (arm 2); toolkit + training + webinars + offered practice facilitation (arm 3)) targeting uptake of electronic health record (EHR) tools focused on guideline-concordant cardioprotective prescribing for patients with diabetes. Outcomes were compared across study arms, to test whether increased support yielded additive improvements, and with 137 non-study CHCs that share the same EHR as the study clinics. Quantitative data from the CHCs’ EHR were used to compare the magnitude of change in guideline-concordant ACE/ARB and statin prescribing, using adjusted Poisson regressions. Qualitative data collected using diverse methods (e.g., interviews, observations) identified factors influencing the quantitative outcomes. Results Outcomes at CHCs receiving higher-intensity support did not improve in an additive pattern. ACE/ARB prescribing did not improve in any CHC group. Statin prescribing improved overall and was significantly greater only in the arm 1 and arm 2 CHCs compared with the non-study CHCs. Factors influencing the finding of no additive impact included: aspects of the EHR tools that reduced their utility, barriers to providing the intended implementation support, and study design elements, e.g., inability to adapt the provided support. Factors influencing overall improvements in statin outcomes likely included a secular trend in awareness of statin prescribing guidelines, selection bias where motivated clinics volunteered for the study, and study participation focusing clinic staff on the targeted outcomes. Conclusions Efforts to implement care guidelines should: ensure adaptability when providing implementation support and conduct formative evaluations to determine the optimal form of such support for a given clinic; consider how study data collection influences adoption; and consider barriers to clinics’ ability to use/accept implementation support as planned. More research is needed on supporting change implementation in under-resourced settings like CHCs. Trial registration ClinicalTrials.gov , NCT02325531. Registered 15 December 2014.

To investigate how familial communication about prostate cancer (PCa) risk and screening affects sons of men with PCa. Qualitative grounded theory. Southern California. 17 Latino sons of PCa survivors. The team conducted semistructured interviews and follow-up interviews. Therefore, the sample includes 25 transcripts. Data were analyzed with a mix of a priori topical codes and grounded theory techniques. Sons were in need of information about familial risk and screening options. They became sensitized to PCa, desired information, and held protective intentions. Hopeful intentions came up against cultural taboos around sex, reproductive health, and intimacy that limited discussions between fathers and sons. Fathers were a valued source of information but play various roles, which affect sons' screening intentions. Open communication between father and son promoted awareness of screening and familial risk. Uncertainty about familial risk and screening options, especially early detection strategies, was exacerbated by cultural taboos around PCa. Fathers could have been primary and credible advocates for shared decision making, but sons had difficulty learning from their fathers' experience. FINDINGS from the study can help inform community-based interventions with Latino families, help to culturally tailor health messaging, and sensitize clinicians to a group that needs concerted counseling about PCa risk and screening.

Abstract There are currently 15.5 million cancer survivors in USA who are increasingly relying on primary care providers for their care. Patient-Centered Medical Homes (PCMHs) have the potential to meet the unique needs of cancer survivors; but, few studies have examined PCMH attributes as potential resources for delivering survivorship care. This study assesses the current care coordination infrastructure in advanced PCMHs, known to be innovative, and explores their capacity to provide cancer survivorship care. We conducted comparative case studies of a purposive sample (n = 9) of PCMHs to examine current care coordination infrastructure and capacity through a mixed- methods analysis. Data included qualitative interviews, quantitative surveys, and fieldnotes collected during 10- to 12-day onsite observations at each practice. Case studies included practices in five states with diverse business models and settings. Eight of the nine practices had National Committee for Quality Assurance Level 3 PCMH recognition. No practices had implemented a systematic approach to cancer survivorship care. We found all practices had a range of electronic population health management tools, care coordinator roles in place for chronic conditions, and strategies or protocols for tracking and managing complex disease groups. We identified potential capacity, as well as barriers, to provide cancer survivorship care using existing care coordination infrastructure developed for other chronic conditions. This existing infrastructure suggests the potential to translate care coordination elements within primary care settings to accelerate the implementation of systematic survivorship care. Innovative primary care practices have the care coordination infrastructure in place that could be adapted to meet the needs of patients with a history of cancer.

To accelerate data sharing and research on traumatic brain injury (TBI), several federal agencies have been collaborating to support the development and implementation of common data elements (CDEs). The first recommendations for CDEs were made in 2010, and were well suited for hospital-based studies of acute TBI in adults. To broaden the utility of the TBI CDEs, experts were asked to update the recommendations to make them relevant to all ages, levels of injury severity, and phases of recovery. The second version of the TBI CDEs (v.2) was organized around four major study types: 1) epidemiological research; 2) studies on acute, hospitalized patients; 3) studies of the rehabilitation for moderate/severe TBI; and 4) mild TBI/concussion research. Given the heterogeneity of TBI, only a small set of core CDEs were found to be relevant across all study types. However, within groups, a much larger set of highly relevant CDEs were identified, and these were called basic CDEs. In addition, an expanded number of supplemental CDEs were specified and recommended for use depending upon the study goals. Version 2 provides a rich data dictionary for TBI research with about 900 CDEs. Many of the CDEs overlap across the study types, which will facilitate comparisons and meta-analysis across studies. Further modifications of the CDEs should be based on evaluation of their usefulness following implementation across a range of studies.

Small cell lung cancer (SCLC) is characterized by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. We show that SCLC patients (37/38) have rare CTC subpopulations co-expressing vascular endothelial-cadherin (VE-cadherin) and cytokeratins consistent with vasculogenic mimicry (VM), a process whereby tumour cells form ‘endothelial-like’ vessels. Single-cell genomic analysis reveals characteristic SCLC genomic changes in both VE-cadherin-positive and -negative CTCs. Higher levels of VM are associated with worse overall survival in 41 limited-stage patients’ biopsies ( P <0.025). VM vessels are also observed in 9/10 CTC patient-derived explants (CDX), where molecular analysis of fractionated VE-cadherin-positive cells uncovered copy-number alterations and mutated TP53, confirming human tumour origin. VE-cadherin is required for VM in NCI-H446 SCLC xenografts, where VM decreases tumour latency and, despite increased cisplatin intra-tumour delivery, decreases cisplatin efficacy. The functional significance of VM in SCLC suggests VM regulation may provide new targets for therapeutic intervention. Small cell lung cancer (SCLC) is characterised by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. The authors show that SCLC patients have a rare CTC subset with a vasculogenic mimicry (VM) phenotype, and that VM is associated with worse overall survival, and alters tumour growth, chemotherapy delivery and efficacy.

To assess the national uptake of the Centers for Disease Control and Prevention's (CDC) core elements of antibiotic stewardship in nursing homes from 2016 to 2018 and the effect of infection prevention and control (IPC) hours on the implementation of the core elements. Retrospective, repeated cross-sectional analysis. US nursing homes. We used the National Healthcare Safety Network (NHSN) Long-Term Care Facility Component annual surveys from 2016 to 2018 to assess nursing home characteristics and percent implementation of the core elements. We used log-binomial regression models to estimate the association between weekly IPC hours and the implementation of all 7 core elements while controlling for confounding by facility characteristics. We included 7,506 surveys from 2016 to 2018. In 2018, 71% of nursing homes reported implementation of all 7 core elements, a 28% increase from 2016. The greatest increases in implementation from 2016 to 2018 were in education (19%), reporting (18%), and drug expertise (15%). In 2018, 71% of nursing homes reported pharmacist involvement in improving antibiotic use, an increase of 27% since 2016. Nursing homes that reported at least 20 hours of IPC activity per week were 14% (95% confidence interval, 7%-20%) more likely to implement all 7 core elements when controlling for facility ownership and affiliation. Nursing homes reported substantial progress in antibiotic stewardship implementation from 2016 to 2018. Improvements in access to drug expertise, education, and reporting antibiotic use may reflect increased stewardship awareness and resource use among nursing home providers under new regulatory requirements. Nursing home stewardship programs may benefit from increased IPC staff hours.

Familial hypercholesterolemia (FH) is characterised by elevated serum levels of low-density lipoprotein cholesterol (LDL-C) and a substantial risk for cardiovascular disease. The autosomal-dominant FH is mostly caused by mutations in LDLR (low density lipoprotein receptor), APOB (apolipoprotein B), and PCSK9 (proprotein convertase subtilisin/kexin). Recently, STAP1 has been suggested as a fourth causative gene. We analyzed STAP1 in 75 hypercholesterolemic patients from Berlin, Germany, who are negative for mutations in canonical FH genes. In 10 patients with negative family history, we additionally screened for disease causing variants in LDLRAP1 (low density lipoprotein receptor adaptor protein 1), associated with autosomal-recessive hypercholesterolemia. We identified one STAP1 variant predicted to be disease causing. To evaluate association of serum lipid levels and STAP1 carrier status, we analyzed 20 individuals from a population based cohort, the Cooperative Health Research in South Tyrol (CHRIS) study, carrying rare STAP1 variants. Out of the same cohort we randomly selected 100 non-carriers as control. In the Berlin FH cohort STAP1 variants were rare. In the CHRIS cohort, we obtained no statistically significant differences between carriers and non-carriers of STAP1 variants with respect to lipid traits. Until such an association has been verified in more individuals with genetic variants in STAP1 , we cannot estimate whether STAP1 generally is a causative gene for FH.

Given the critical role of fatherhood in child development and the significant challenges faced by fathers in underserved communities, there is a pressing need to better understand the specific barriers they encounter. This exploratory mixed-methods study examines the prevalence of adverse childhood experiences (ACEs) among fathers, including English, Spanish, and Creole speakers, and explores how social determinants of health exacerbate these barriers. Quantitative data were collected from June 2022–2023 using REDCap survey software. Additionally, three focus groups were conducted with 18 fathers residing in Palm Beach County (PBC), each group based on the primary language spoken at home. The focus groups were conducted in person via the Healthy Mothers Healthy Babies Coalition (HMHB) outreach team at community centers within the PBC. Stated barriers to fatherhood were thematically classified according into three main themes: (1) limited access to and knowledge of resources in the community; (2) challenges in navigating new roles, resources, and fatherhood responsibilities; and (3) important values in parenting. Over 40% of the fathers reported barriers to being involved in their child’s life. The most frequent barriers included work (35.4%) and lack of transportation distance (12.5%). Bivariate analysis using the fisher’s exact test showed a significant association between scoring greater than 4 on the ACE criteria checklist and experiencing barriers to being involved in the child’s life (p-value = 0.013). Findings from this study aim to inform the development of culturally tailored interventions that address disparities in fatherhood support, ultimately contributing to improved outcomes for both fathers and their children.

Purpose Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA , and more rarely in PPP2R1A . Here, we aimed to better understand the latter by characterizing 30 individuals with de novo and often recurrent variants in this PP2A scaffolding Aα subunit. Methods Most cases were identified through routine clinical diagnostics. Variants were biochemically characterized for phosphatase activity and interaction with other PP2A subunits. Results We describe 30 individuals with 16 different variants in PPP2R1A , 21 of whom had variants not previously reported. The severity of developmental delay ranged from mild learning problems to severe intellectual disability (ID) with or without epilepsy. Common features were language delay, hypotonia, and hypermobile joints. Macrocephaly was only seen in individuals without B55α subunit-binding deficit, and these patients had less severe ID and no seizures. Biochemically more disruptive variants with impaired B55α but increased striatin binding were associated with profound ID, epilepsy, corpus callosum hypoplasia, and sometimes microcephaly. Conclusion We significantly expand the phenotypic spectrum of PPP2R1A -related NDD, revealing a broader clinical presentation of the patients and that the functional consequences of the variants are more diverse than previously reported.

This study examined reading, math, writing, social, behavioral, and communication learning goals for a large, national sample of elementary students with complex support needs served in one of four types of educational placements. Each goal was coded for three quality characteristics: (1) strengths-focus; (2) inclusion of self-determination skills; and (3) description of the context and content of goals, and identification of needed supports. The findings suggest ongoing issues with the expectations in goals for students with complex support needs across placement types, consistent with past research. There was a general lack of focus on student-directed learning and activities as well as a lack of identification of student-initiated supports. Goal quality characteristics varied across goal domains and placements; descriptive findings suggest that goals aligned with academic standards and social-behavioral-communication competencies were more common for students in inclusive general education classrooms. Implications for research and practice are described.