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Background: Advance care planning (ACP) is the process of having conversations with patients to ensure preferences are known and support patient healthcare goals. ACP and the Age-Friendly Health Systems (AFHS) Initiative's, "What Matters," are synergistic approaches to patient-centered conversations. Implementation and measurement of ACP in primary care (PC) are variables in quality and consistency. We examined whether participation in an ACP learning collaborative (LC) would improve knowledge and ability to conduct ACP discussions and increase the frequency of documented ACP in participating practices., Methods: The WWAMI (Washington, Wyoming, Alaska, Montana, and Idaho) region Practice and Research Network (WPRN) and the Northwest Geriatrics Workforce Enhancement Center collaboratively organized a 9-month virtual LC. It consisted of 4 synchronous, 1.5-h sessions, technical support, and a panel of ACP experts. A Wilcoxon rank sum test assessed differences in knowledge from a pre-post survey. Documentation of ACP in the EHR was collected after at least one plan-do-study-act cycle., Results: We enrolled 17 participants from 6 PC practices (3 hospital-affiliated; 3 Federally Qualified Health Centers) from the WPRN. Two practices did not complete all LC activities. There was a trend toward increased ACP knowledge and skills overall especially in having discussions patients and families (pre-mean 2.9 [SD = 0.7]/post-mean 4.0[SD = 1.1], p < 0.05). 4/6 practices observed an increase in EHR documentation post-collaborative (median 16.3%, IQR 1.3%-36.9%)., Conclusions: The LC increased PC providers knowledge and skills of ACP and AFHS's What Matters, reported ACP EHR documentation, and contributed to practice change., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Background: Use of the Project ECHO® (Extension for Community Healthcare Outcomes) model in geriatrics has increased dramatically largely because of the Health Resources and Services Administration-funded Geriatrics Workforce Enhancement Programs (GWEP) utilizing it as a key tool for age-friendly, interprofessional workforce development. This manuscript describes the scope and impact of geriatrics ECHOs under the GWEP., Methods: A survey of GWEPs was conducted to measure the reach, foci, evaluation methods, and other characteristics of ECHO networks., Results: All 48 (100%) GWEPs responded to the survey, and 30 (63%) reported using ECHO. GWEP ECHOs have both rural and urban-underserved reach across the United States, and their hub teams include many health professions. Age-friendly care is incorporated through multiple methods and is taught across foci including primary care, dementia, long term care, and novel topics. GWEP ECHOs have many academic and community partners including Area Agencies on Aging, and reach varied health professions, trainees, and caregivers. Geriatrics ECHOs collect outcomes across the evidence continuum including the community-level outcome of Age-Friendly Health System designation., Conclusions: The ECHO model has been widely adopted by GWEPs as a key approach for workforce training in age-friendly care. Project ECHO is a valuable tool to expand interprofessional training for the geriatrics workforce, particularly for interprofessional teams in rural and underserved areas., (© 2024 The American Geriatrics Society.)

Epidemiological evidence links chemical exposure with type 2 diabetes (T2DM) risk and prevalence. Chemical exposure may therefore also limit success of weight loss or restoration of glycemic control during calorie restricted diets. Few human studies examine this hypothesis. This systematic review and clustered meta-analysis examines preclinical evidence that exposure to anthropogenic environmental contaminants impedes weight loss and resumption of glycemic control during calorie restriction. Of five eligible papers from 212 unique citations, four used C57BL/6 mice and one used Sprague Dawley rats. In four the animals received high fat diets to induce obesity and impaired glycemic control. All examined persistent organic pollutants (POPs). Polychlorinated biphenyl (PCB) 77 exposure did not affect final mass (standardised mean difference (SMD) = -0.35 [-1.09, 0.39]; n = 5 (experiments); n = 3 (papers)), or response to insulin in insulin tolerance tests (SMD = -1.54 [-3.25, 0.16] n = 3 (experiments); n = 2 (papers)), but impaired glucose control in glucose tolerance tests (SMD = -1.30 [-1.96, -0.63]; n = 6 (experiments); n = 3 (papers)). The impaired glycemic control following perfluoro-octane sulphonic acid (PFOS) exposure and enhanced mass loss following dichlorodiphenyltrichloroethane (DDT) exposure have not been replicated. Animal studies thus suggest some chemical groups, especially PCB and PFOS, could impair glucose control management during calorie restriction, similar to conclusions from limited existing clinical studies. We discuss the research that is urgently required to inform weight management services that are now the mainstay prevention initiative for T2DM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Cesarean hysterectomy is generally presumed to decrease maternal morbidity and mortality secondary to placenta accreta spectrum disorder. Recently, uterine-sparing techniques have been introduced in conservative management of placenta accreta spectrum disorder to preserve fertility and potentially reduce surgical complications. However, despite patients often expressing the intention for future conception, few data are available regarding the subsequent pregnancy outcomes after conservative management of placenta accreta spectrum disorder. Thus, we aimed to perform a systematic review and meta-analysis to assess these outcomes., Data Sources: PubMed, Scopus, and Web of Science databases were searched from inception to September 2022., Study Eligibility Criteria: We included all studies, with the exception of case studies, that reported the first subsequent pregnancy outcomes in individuals with a history of placenta accreta spectrum disorder who underwent any type of conservative management., Methods: The R programming language with the "meta" package was used. The random-effects model and inverse variance method were used to pool the proportion of pregnancy outcomes., Results: We identified 5 studies involving 1458 participants that were eligible for quantitative synthesis. The type of conservative management included placenta left in situ (n=1) and resection surgery (n=1), and was not reported in 3 studies. The rate of placenta accreta spectrum disorder recurrence in the subsequent pregnancy was 11.8% (95% confidence interval, 1.1-60.3; I 2 =86.4%), and 1.9% (95% confidence interval, 0.0-34.1; I 2 =82.4%) of participants underwent cesarean hysterectomy. Postpartum hemorrhage occurred in 10.3% (95% confidence interval, 0.3-81.4; I 2 =96.7%). A composite adverse maternal outcome was reported in 22.7% of participants (95% confidence interval, 0.0-99.4; I 2 =56.3%)., Conclusion: Favorable pregnancy outcome is possible following successful conservation of the uterus in a placenta accreta spectrum disorder pregnancy. Approximately 1 out of 4 subsequent pregnancies following conservative management of placenta accreta spectrum disorder had considerable adverse maternal outcomes. Given such high incidence of adverse outcomes and morbidity, patient and provider preparation is vital when managing this population., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In a typical G protein coupled receptor drug discovery campaign, an in vitro primary functional screening assay is often established in a recombinant system overexpressing the target of interest, which offers advantages with respect to overall throughput and robustness of compound testing. Subsequently, compounds are then progressed into more physiologically relevant but lower throughput ex vivo primary cell assays and finally in vivo studies. Here we describe a dynamic mass redistribution (DMR) assay that has been developed in a format suitable to support medium throughput drug screening in primary human neutrophils. Neutrophils are known to express both CXC chemokine receptor (CXCR) 1 and CXCR2 that are thought to play significant roles in various inflammatory disorders and cancer. Using multiple relevant chemokine ligands and a range of selective and nonselective small and large molecule antagonists that block CXCR1 and CXCR2 responses, we demonstrate distinct pharmacological profiles in neutrophil DMR from those observed in recombinant assays but predictive of activity in neutrophil chemotaxis and CD11b upregulation, a validated target engagement marker previously used in clinical studies of CXCR2 antagonists. The primary human neutrophil DMR cell system is highly reproducible, robust, and less prone to donor variability observed in CD11b and chemotaxis assays and thus provides a unique, more physiologically relevant, and higher throughput assay to support drug discovery and translation to early clinical trials. SIGNIFICANCE STATEMENT: Neutrophil dynamic mass redistribution assays provide a higher throughput screening assay to profile compounds in primary cells earlier in the screening cascade enabling a higher level of confidence in progressing the development of compounds toward the clinic. This is particularly important for chemokine receptors where redundancy contributes to a lack of correlation between recombinant screening assays and primary cells, with the coexpression of related receptors confounding results., (Copyright © 2024 by The Author(s).)

Objective: Somatostatin receptor ligands have come to play a pivotal role in the treatment of both ACTH- and GH-secreting pituitary adenomas. Clinical efficacy averages 30-50%, thus a considerable number of patients with Cushing's disease or acromegaly remain unresponsive to this therapeutic approach. HTL0030310 is a new somatostatin receptor ligand selective for subtype 5 over subtype 2, thus with a different receptor profile compared to clinical somatostatin receptor ligands., Design: Assessment of the effect of HTL0030310 on hormone secretion in human ACTH- and GH-secreting pituitary adenomas in vitro., Methods: Primary cultures from 3 ACTH-secreting and 5 GH-secreting pituitary adenomas were treated with 1, 10 and 100 nM HTL0030310 alone or with 10 nM CRH or GHRH, respectively. Parallel incubations with 10 nM pasireotide were also carried out. ACTH and GH secretion were assessed after 4 and 24 hour incubation; SSTR2, SSTR3, SSTR5, GH and POMC expression were evaluated after 24 hours., Results: HTL0030310 reduced unchallenged ACTH and POMC levels up to 50% in 2 ACTH-secreting adenomas and blunted CRH-stimulated ACTH/POMC by 20-70% in all 3 specimens. A reduction in spontaneous GH secretion was observed in 4 GH-secreting adenomas and in 2 specimens during GHRH co-incubation. SSTRs expression was detected in all specimens., Conclusions: This first study on a novel somatostatin receptor 5-preferring ligand indicates that HTL0030310 can inhibit hormonal secretion in human ACTH- and GH-secreting pituitary adenomas. These findings suggest a potential new avenue for somatostatin ligands in the treatment of Cushing's disease and acromegaly., Competing Interests: Conflict of interest: The following authors are employees for Sosei Heptares: C.P.M., E.S., D.H., A.G., K.A.B., A.J.H.B., and M.B. D.R., S.A., G.O., M.B., D.F., M.P.T., M.L., G.L., C.S., and F.P.G. have no conflicts of interest to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology.)