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1.
J Am Geriatr Soc ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822739

RESUMO

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.

2.
J Am Pharm Assoc (2003) ; : 102106, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38663533

RESUMO

BACKGROUND: Diabetes is the eighth leading cause of death and has a substantial impact on the United States (U.S.) health care system. Recent changes to major insurance formularies allow for increased access to continuous glucose monitors (CGM). Community pharmacists routinely assist and educate patients about diabetes care, including usage of CGM. OBJECTIVES: The purpose of this study was to evaluate the clinical impact of a community pharmacist remote CGM monitoring service on patients' glycemic metrics. Patient completion of comprehensive diabetes standards of care and pharmacist interventions and recommendations were assessed as secondary objectives. METHODS: This study was a prospective, feasibility study conducted at two pharmacies within one regional division of a large community pharmacy chain between November 2022 and June 2023. A pharmacist conducted patient enrollment visits and remotely monitored CGM glycemic metrics via cloud-based platforms per the study protocol. CGM glycemic metrics were evaluated for each patient three months pre- and post-study enrollment, including time above range (TAR), time in range (TIR), time below range (TBR), glucose management indicator (GMI), average glucose, CGM utilization rate, and glucose variability. Metrics were evaluated for statistical significance using the Wilcoxon signed-rank test and descriptive statistics. RESULTS: Pharmacists enrolled 36 patients in this study with 20 patients completing the full three-month study period per protocol. There was a statistically significant improvement in three of eight glycemic metrics (very high TAR, TIR, and average glucose). Specifically, TIR had the largest improvement from 61.8% pre-enrollment to 69.9% (p < 0.006) post-enrollment. All other pertinent glycemic metrics displayed improvements but were not statistically significant. CONCLUSION: The results demonstrate clinically and statistically significant improvements in several glycemic metrics for patients who participated in the community pharmacist-led remote CGM monitoring service, which may result in improved diabetes control and fewer long-term diabetes-related health complications.

3.
Cancers (Basel) ; 16(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38339293

RESUMO

PURPOSE: To assess the efficacy of various machine learning (ML) algorithms in predicting late-stage colorectal cancer (CRC) diagnoses against the backdrop of socio-economic and regional healthcare disparities. METHODS: An innovative theoretical framework was developed to integrate individual- and census tract-level social determinants of health (SDOH) with sociodemographic factors. A comparative analysis of the ML models was conducted using key performance metrics such as AUC-ROC to evaluate their predictive accuracy. Spatio-temporal analysis was used to identify disparities in late-stage CRC diagnosis probabilities. RESULTS: Gradient boosting emerged as the superior model, with the top predictors for late-stage CRC diagnosis being anatomic site, year of diagnosis, age, proximity to superfund sites, and primary payer. Spatio-temporal clusters highlighted geographic areas with a statistically significant high probability of late-stage diagnoses, emphasizing the need for targeted healthcare interventions. CONCLUSIONS: This research underlines the potential of ML in enhancing the prognostic predictions in oncology, particularly in CRC. The gradient boosting model, with its robust performance, holds promise for deployment in healthcare systems to aid early detection and formulate localized cancer prevention strategies. The study's methodology demonstrates a significant step toward utilizing AI in public health to mitigate disparities and improve cancer care outcomes.

6.
Fam Med ; 55(7): 452-459, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37450845

RESUMO

BACKGROUND AND OBJECTIVES: Opioid use and overdose remain a central and worsening public health emergency in the United States and abroad. Efforts to expand treatment have struggled to match the rising incidence of opioid use disorder (OUD), and treating patients in primary care settings represents one of the most promising opportunities to meet this need. Learning collaboratives (LCs) are one evidence-based strategy to improve implementation of medication treatment for opioid use disorder (MOUD) in primary care. METHODS: We developed and studied a multidisciplinary MOUD learning collaborative involving six underserved primary care clinics. We used a mixed-methods approach to assess needs, develop curriculum, and evaluate outcomes from these clinics. RESULTS: We recruited six clinics to participate in the collaborative. Half had an established MOUD program. Approximately 80% of participants achieved their organizational quality improvement goals for the collaborative. After the collaborative, participants also reported a significant increase in their perceived competence to implement/improve a MOUD program (pre-LC competence=2.80, post-LC competence=6.33/10, P=.02). The most consistent barrier we identified was stigma around OUD and its effects on patients' ability to access services and staff/provider ability to provide services. The most frequent enablers of program success were trainee interest, organizational leadership support, and a dedicated MOUD care team. CONCLUSIONS: Organizations used clinical and systems improvement knowledge to enhance their existing programs or to take steps to create new programs. All participants identified the need for additional staff/clinician training, especially to overcome stigma around OUD. The outcomes demonstrated the crucial importance of long-term organizational support for program success.


Assuntos
Overdose de Drogas , Transtornos Relacionados ao Uso de Opioides , Humanos , Aprendizagem , Currículo , Transtornos Relacionados ao Uso de Opioides/terapia , Atenção Primária à Saúde , Analgésicos Opioides
7.
Nurs Womens Health ; 27(3): 220-230, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37150210

RESUMO

Breast cancer is well recognized as a leading type of cancer affecting women in the United States. Although breast cancer screening is well supported in the literature, there is a lack of clear agreement regarding which breast cancer risk calculating tools should be used to develop personalized screening regimens. In this review of 11 primary articles published from 2017 through 2022, we assess current evidence on breast cancer risk assessment in outpatient clinic and mammography settings and the pivotal role of health care providers in influencing patients' choices regarding individualized screenings. Risk assessment is strongly recommended by multiple clinical practice guidelines, yet there is inadequate evidence to endorse one risk assessment tool as best practice. Further research is needed to integrate risk assessment within the clinic workflow and screening encounters. Patient-centered communication and shared decision-making are critical components for managing each woman's perceived risk and objective risk for breast cancer.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Estados Unidos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Tomada de Decisões , Mamografia , Medição de Risco , Tomada de Decisão Compartilhada , Detecção Precoce de Câncer , Programas de Rastreamento
8.
BMC Health Serv Res ; 23(1): 174, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36810066

RESUMO

BACKGROUND: In 2019-2020, with National Cancer Institute funding, seven implementation laboratory (I-Lab) partnerships between scientists and stakeholders in 'real-world' settings working to implement evidence-based interventions were developed within the Implementation Science Centers in Cancer Control (ISC3) consortium. This paper describes and compares approaches to the initial development of seven I-Labs in order to gain an understanding of the development of research partnerships representing various implementation science designs. METHODS: In April-June 2021, members of the ISC3 Implementation Laboratories workgroup interviewed research teams involved in I-Lab development in each center. This cross-sectional study used semi-structured interviews and case-study-based methods to collect and analyze data about I-Lab designs and activities. Interview notes were analyzed to identify a set of comparable domains across sites. These domains served as the framework for seven case descriptions summarizing design decisions and partnership elements across sites. RESULTS: Domains identified from interviews as comparable across sites included engagement of community and clinical I-Lab members in research activities, data sources, engagement methods, dissemination strategies, and health equity. The I-Labs use a variety of research partnership designs to support engagement including participatory research, community-engaged research, and learning health systems of embedded research. Regarding data, I-Labs in which members use common electronic health records (EHRs) leverage these both as a data source and a digital implementation strategy. I-Labs without a shared EHR among partners also leverage other sources for research or surveillance, most commonly qualitative data, surveys, and public health data systems. All seven I-Labs use advisory boards or partnership meetings to engage with members; six use stakeholder interviews and regular communications. Most (70%) tools or methods used to engage I-Lab members such as advisory groups, coalitions, or regular communications, were pre-existing. Think tanks, which two I-Labs developed, represented novel engagement approaches. To disseminate research results, all centers developed web-based products, and most (n = 6) use publications, learning collaboratives, and community forums. Important variations emerged in approaches to health equity, ranging from partnering with members serving historically marginalized populations to the development of novel methods. CONCLUSIONS: The development of the ISC3 implementation laboratories, which represented a variety of research partnership designs, offers the opportunity to advance understanding of how researchers developed and built partnerships to effectively engage stakeholders throughout the cancer control research lifecycle. In future years, we will be able to share lessons learned for the development and sustainment of implementation laboratories.


Assuntos
Laboratórios , Neoplasias , Humanos , Estudos Transversais , Atenção à Saúde , Comunicação
9.
Pharm Res ; 40(7): 1641-1656, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36720831

RESUMO

Administration of long-acting injectable suspensions is an increasingly common approach to increasing patient compliance and improving therapeutic efficacy through less frequent dosing. While several long-acting suspensions have recently been marketed, parameters modulating drug absorption from suspension-based formulations are not well understood. Further, methods for predicting clinical pharmacokinetic data from preclinical studies are not well established. Together, these limitations hamper compound selection, formulation design and formulation selection through heavy reliance on iterative optimization in preclinical and clinical studies. This article identifies key parameters influencing absorption from suspension-based formulations through compilation and analysis of preclinical and clinical pharmacokinetic data of seven compounds marketed as suspensions; achievable margins for predicting the clinical dose and input rate from preclinical studies as a function of the preclinical species, the clinical injection location and the intended therapeutic duration were also established.


Assuntos
Suspensões , Humanos , Estudos Retrospectivos , Injeções
10.
Dalton Trans ; 51(37): 14079-14087, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-35975743

RESUMO

Ion pair receptors typically contain two separate binding sites, for the metal and the anion respectively. Here we report a less synthetically demanding approach, whereby we prepared a family of ion pair sensors based on a rhodamine fluorescent scaffold containing a tunable cation binding motif. When exposed to ion pairs, a competition for the metal ion is established between these ligands and anions. Structural and spectroscopic evidence showed that anions bind through weaker secondary interactions in the metal's outer coordination sphere and their presence influences the optical spectroscopic properties of the coordination complex in distinctive ways. The relationship between the binding site's metal affinity and its tunable properties, and the sensors' discriminatory power for anions was explained as a function of the metal ion's binding preferences. These effects were also exploited to discriminate cations and anions concurrently through multivariate data analysis methods.


Assuntos
Metais , Ânions/química , Cátions , Ligantes , Metais/química , Rodaminas
11.
J Biol Chem ; 298(9): 102233, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35798139

RESUMO

A major physiological role of hERG1 (human Ether-á-go-go-Related Gene 1) potassium channels is to repolarize cardiac action potentials. Two isoforms, hERG1a and hERG1b, associate to form the potassium current IKr in cardiomyocytes. Inherited mutations in hERG1a or hERG1b cause prolonged cardiac repolarization, long QT syndrome, and sudden death arrhythmia. hERG1a subunits assemble with and enhance the number of hERG1b subunits at the plasma membrane, but the mechanism for the increase in hERG1b by hERG1a is not well understood. Here, we report that the hERG1a N-terminal region expressed in trans with hERG1b markedly increased hERG1b currents and increased biotin-labeled hERG1b protein at the membrane surface. hERG1b channels with a deletion of the N-terminal 1b domain did not have a measurable increase in current or biotinylated protein when coexpressed with hERG1a N-terminal regions, indicating that the 1b domain was required for the increase in hERG1b. Using a biochemical pull-down interaction assay and a FRET hybridization experiment, we detected a direct interaction between the hERG1a N-terminal region and the hERG1b N-terminal region. Using engineered deletions and alanine mutagenesis, we identified a short span of amino acids at positions 216 to 220 within the hERG1a "N-linker" region that were necessary for the upregulation of hERG1b. We propose that direct structural interactions between the hERG1a N-linker region and the hERG1b 1b domain increase hERG1b at the plasma membrane. Mechanisms regulating hERG1a and hERG1b are likely critical for cardiac function, may be disrupted by long QT syndrome mutants, and serve as potential targets for therapeutics.


Assuntos
Canais de Potássio Éter-A-Go-Go , Síndrome do QT Longo , Alanina/química , Alanina/genética , Biotina/química , Canais de Potássio Éter-A-Go-Go/química , Canais de Potássio Éter-A-Go-Go/genética , Canais de Potássio Éter-A-Go-Go/metabolismo , Humanos , Síndrome do QT Longo/genética , Síndrome do QT Longo/metabolismo , Mutagênese , Domínios Proteicos , Regulação para Cima
13.
J Am Pharm Assoc (2003) ; 62(4S): S35-S40.e1, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34930681

RESUMO

BACKGROUND: Opioid overdose deaths accounted for approximately 69.5% of the total drug overdoses in the United States in 2018. In the same year, the Centers for Disease Control and Prevention estimates that around 9 million opportunities to dispense naloxone to high-risk patients were missed. Community pharmacists are equipped to help all patients obtain naloxone to prevent opioid-related overdoses. OBJECTIVES: The purpose of this study was to determine the impact of mandatory alerts on the dispensing of naloxone by pharmacists using a physician-approved protocol. The primary objective of this study was to evaluate the change in the number of dispensed naloxone prescriptions via physician-approved protocol compared with the same time period in the previous year. The secondary objective was to evaluate the pharmacists' knowledge and confidence dispensing naloxone via physician-approved protocol. PRACTICE DESCRIPTION: A system-generated mandatory alert that prompted pharmacists to assess the need for naloxone and initiate and dispense as appropriate via a physician-approved protocol was implemented in 5 pharmacies of a large community pharmacy chain between June and July 2020. PRACTICE INNOVATION: A technology enhancement was designed that automatically created a mandatory alert in the pharmacy management system for all patients who were dispensed a long-acting opioid medication to prompt pharmacists to initiate and dispense naloxone as appropriate. EVALUATION METHODS: The impact of the mandatory alert was evaluated by assessing patients' medication fill history in the pharmacy management system to determine the change in naloxone prescriptions dispensed. RESULTS: During the intervention period, pharmacists initiated and dispensed 34 incremental naloxone prescriptions via a physician-approved protocol compared with the same time period in the previous year. CONCLUSION: The results illustrated that system-generated mandatory alerts prompting pharmacist intervention can effectively increase pharmacist utilization of a physician-approved protocol, resulting in increased naloxone prescriptions dispensed to high-risk patients.


Assuntos
Overdose de Drogas , Transtornos Relacionados ao Uso de Opioides , Farmácias , Analgésicos Opioides/uso terapêutico , Overdose de Drogas/tratamento farmacológico , Overdose de Drogas/prevenção & controle , Humanos , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Farmacêuticos , Prescrições , Estados Unidos
14.
Sci Rep ; 11(1): 24245, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930978

RESUMO

Systemic lupus erythematosus (SLE) is a devastating autoimmune disorder characterized by failure of self-tolerance with resultant production of autoreactive antibodies. The etiology of this syndrome is complex, involving perturbations in immune cell signaling and development. The NZBWF1 mouse spontaneously develops a lupus-like syndrome and has been widely used as a model of SLE for over 60 years. The NZBWF1 model represents the F1 generation of a cross between New Zealand Black (NZB) and New Zealand White (NZW) mice. In order to better understand the factors that contribute to the development of autoimmunity, single cell RNA sequencing was conducted using the bone marrow from female NZBWF1 mice prior to the development of overt disease. The results were contrasted with single cell RNA sequencing results from the two parental strains. The expected findings of B cell abundance and upregulation, and evidence of interferon signaling were validated in this model. In addition, several novel areas of inquiry were identified. Most notably, the data showed a marked upregulation of the ferritin light chain across all cell types in the NZBWF1 mice compared to parental controls. This data can serve as a gene expression atlas of all hematopoietic cells in the NZBWF1 bone marrow prior to the development of autoimmunity.


Assuntos
Doenças Autoimunes/imunologia , Sequência de Bases , Lúpus Eritematoso Sistêmico/imunologia , Animais , Autoanticorpos/imunologia , Autoimunidade , Linfócitos B , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Tolerância Imunológica , Funções Verossimilhança , Camundongos , Fenótipo , RNA/análise
15.
Am J Physiol Renal Physiol ; 320(6): F1093-F1105, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33843272

RESUMO

Hypertension and diabetes are the greatest factors influencing the progression of chronic kidney disease (CKD). Investigation into the role of nephron number in CKD alone or with hypertension has revealed a strong inverse relationship between the two; however, not much is known about the connection between nephron number and diabetic kidney disease. The heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, a novel model of nephron deficiency, provides a unique opportunity to study the association between nephron number and hypertension and diabetes on CKD. HSRA rats exhibit failure of one kidney to develop in 50-75% of offspring, whereas the remaining offspring are born with two kidneys. Rats born with one kidney (HSRA-S) develop significant renal injury with age compared with two-kidney littermates (HSRA-C). The induction of hypertension as a secondary stressor leads to significantly more renal injury in HSRA-S compared with HSRA-C rats and nephrectomized HSRA-C (HSRA-UNX) rats. The present study sought to address the hypothesis that nephron deficiency in the HSRA rat would hasten renal injury in the presence of a secondary stressor of hyperglycemia. HSRA animals did not exhibit diabetes-related traits at any age; thus, streptozotocin (STZ) was used to induce hyperglycemia in HSRA-S, HSRA-C, and HSRA-UNX rats. STZ- and vehicle-treated animals were followed for 15 wk. STZ-treated animals developed robust hyperglycemia, but in contrast to the response to hypertension, neither HSRA-S nor HSRA-UNX animals developed proteinuria compared with vehicle treatment. In total, our data indicate that hyperglycemia from STZ alone does not have a significant impact on the onset or progression of injury in young one-kidney HSRA animals.NEW & NOTEWORTHY The HSRA rat, a novel model of nephron deficiency, provides a unique opportunity to study the association between nephron number and confounding cardiovascular complications that impact kidney health. Although hypertension was previously shown to exacerbate renal injury in young HSRA animals, diabetic hyperglycemia did not lead to worse renal injury, suggesting that nephron number has limited impact on kidney injury, at least in this model.


Assuntos
Envelhecimento , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/patologia , Rim Único/metabolismo , Animais , Hiperglicemia , Rim/fisiopatologia , Masculino , Ratos , Ratos Endogâmicos
16.
Implement Sci Commun ; 2(1): 44, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33892822

RESUMO

BACKGROUND: Evidence-based interventions (EBIs) could reduce cervical cancer deaths by 90%, colorectal cancer deaths by 70%, and lung cancer deaths by 95% if widely and effectively implemented in the USA. Yet, EBI implementation, when it occurs, is often suboptimal. This manuscript outlines the protocol for Optimizing Implementation in Cancer Control (OPTICC), a new implementation science center funded as part of the National Cancer Institute Implementation Science Consortium. OPTICC is designed to address three aims. Aim 1 is to develop a research program that supports developing, testing, and refining of innovative, efficient methods for optimizing EBI implementation in cancer control. Aim 2 is to support a diverse implementation laboratory of clinical and community partners to conduct rapid, implementation studies anywhere along the cancer care continuum for a wide range of cancers. Aim 3 is to build implementation science capacity in cancer control by training new investigators, engaging established investigators in cancer-focused implementation science, and contributing to the Implementation Science Consortium in Cancer. METHODS: Three cores serve as OPTICC's foundation. The Administrative Core plans coordinates and evaluates the Center's activities and leads its capacity-building efforts. The Implementation Laboratory Core (I-Lab) coordinates a network of diverse clinical and community sites, wherein studies are conducted to optimize EBI implementation, implement cancer control EBIs, and shape the Center's agenda. The Research Program Core conducts innovative implementation studies, measurement and methods studies, and pilot studies that advance the Center's theme. A three-stage approach to optimizing EBI implementation is taken-(I) identify and prioritize determinants, (II) match strategies, and (III) optimize strategies-that is informed by a transdisciplinary team of experts leveraging multiphase optimization strategies and criteria, user-centered design, and agile science. DISCUSSION: OPTICC will develop, test, and refine efficient and economical methods for optimizing EBI implementation by building implementation science capacity in cancer researchers through applications with our I-Lab partners. Once refined, OPTICC will disseminate its methods as toolkits accompanied by massive open online courses, and an interactive website, the latter of which seeks to simultaneously accumulate knowledge across OPTICC studies.

17.
Pharmacy (Basel) ; 9(1)2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673541

RESUMO

BACKGROUND: Technology is increasingly used to enhance pharmacy education. We sought to evaluate student learning and preparedness for community introductory pharmacy practice experiences (IPPEs) after implementation of "MyDispense" into experiential education. METHODS: Both first-year pharmacy students and assigned community IPPE preceptors were eligible. Students were stratified based on previous community pharmacy experience (< or ≥ 50 h), then randomized to complete MyDispense exercises before IPPE (group A) or after 24-32 h of IPPE (group B). We evaluated preceptors' assessment of student readiness using a 6-item Likert scale survey and students' readiness and opinion of MyDispense using an anonymous 9-item survey. Descriptive statistics were used to characterize data. The Mann-Whitney U test was used to compare groups and a p-value < 0.05 was considered statistically significant. RESULTS: Of 177 eligible students, 155 were randomized and 56 completed study. Group A included 32 students; 56.3% had prior community practice experience. Group B included 24 students; 50% had prior community practice experience. Forty-eight preceptors were enrolled. Students who completed exercises before rotation received higher preceptor scores for patient counseling of self-care and of medications (p < 0.05 for both). Students self-assessed their counseling skills lower than all other skills; 30.4% and 42.9% of students felt mostly or always prepared to counsel for self-care and medications, respectively. Students found MyDispense straightforward, realistic, and appreciated the ability to practice in a safe, electronic, community pharmacy, patient-care environment. CONCLUSION: Simulation-based software, such as MyDispense, can enhance learner understanding of the prescription fill and counseling process in a community pharmacy practice setting.

18.
Sci Rep ; 11(1): 2071, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33483609

RESUMO

Chronic kidney disease (CKD), which can ultimately progress to kidney failure, is influenced by genetics and the environment. Genes identified in human genome wide association studies (GWAS) explain only a small proportion of the heritable variation and lack functional validation, indicating the need for additional model systems. Outbred heterogeneous stock (HS) rats have been used for genetic fine-mapping of complex traits, but have not previously been used for CKD traits. We performed GWAS for urinary protein excretion (UPE) and CKD related serum biochemistries in 245 male HS rats. Quantitative trait loci (QTL) were identified using a linear mixed effect model that tested for association with imputed genotypes. Candidate genes were identified using bioinformatics tools and targeted RNAseq followed by testing in a novel in vitro model of human tubule, hypoxia-induced damage. We identified two QTL for UPE and five for serum biochemistries. Protein modeling identified a missense variant within Septin 8 (Sept8) as a candidate for UPE. Sept8/SEPTIN8 expression increased in HS rats with elevated UPE and tubulointerstitial injury and in the in vitro hypoxia model. SEPTIN8 is detected within proximal tubule cells in human kidney samples and localizes with acetyl-alpha tubulin in the culture system. After hypoxia, SEPTIN8 staining becomes diffuse and appears to relocalize with actin. These data suggest a role of SEPTIN8 in cellular organization and structure in response to environmental stress. This study demonstrates that integration of a rat genetic model with an environmentally induced tubule damage system identifies Sept8/SEPTIN8 and informs novel aspects of the complex gene by environmental interactions contributing to CKD risk.


Assuntos
Túbulos Renais/patologia , Rim/patologia , Septinas/genética , Animais , Hipóxia Celular , Efeito Fundador , Haplótipos , Humanos , Masculino , Ratos
19.
J Am Pharm Assoc (2003) ; 61(4S): S154-S160, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33451969

RESUMO

BACKGROUND: Medication nonadherence is associated with increased morbidity and mortality, higher rates of hospital admissions, and increased health care costs. Nearly half of patients do not take their medications as prescribed leading to poor outcomes. Patients with chronic conditions, especially those with depression, demonstrate lower adherence to their medications. Community pharmacists routinely address demographic and sociocultural barriers and are equipped to screen for and assist with behavioral barriers to medication adherence. OBJECTIVES: The purpose of this study was to assess the feasibility and impact of conducting a depression screening as part of a holistic adherence assessment. The primary objective of this project was to evaluate the impact of a holistic adherence assessment on medication adherence. The secondary objectives evaluated patients' barriers to adherence, Patient Health Questionnaires 2 and 9 (PHQ-2 and 9) results, and pharmacist interventions. PRACTICE DESCRIPTION: Pharmacists conducted a holistic adherence assessment and performed a depression screening for patients who were nonadherent or at risk of becoming nonadherent to their chronic medications. PRACTICE INNOVATION: A pharmacist-led holistic adherence assessment implemented in 2 pharmacies of a large community pharmacy chain between January and May 2020. EVALUATION METHODS: The impact on medication adherence was evaluated by assessing if patients received the next fill of their chronic medication on time after the holistic adherence assessment. RESULTS: During the study period, 69 patients completed the holistic adherence assessment and were screened for depression. A total of 12 patients (17.4%) screened positive on the PHQ-2, and 6 patients (8.7%) screened positive on the PHQ-9. After the intervention, 42 patients (60.9%) received the next fill of their targeted chronic medication on time, and 27 patients (39.1%) were late to pick up their next fill. CONCLUSION: The results illustrated that community pharmacists can incorporate a depression screening into a holistic adherence assessment effectively to screen for behavioral barriers that may affect medication adherence.


Assuntos
Serviços Comunitários de Farmácia , Farmácias , Depressão/diagnóstico , Depressão/tratamento farmacológico , Custos de Cuidados de Saúde , Humanos , Adesão à Medicação , Farmacêuticos
20.
Physiol Genomics ; 53(3): 125-136, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33491590

RESUMO

Preeclampsia is a progressive hypertensive disorder of pregnancy affecting 2%-8% of pregnancies globally. Preexisting chronic hypertension is a major risk factor associated with developing preeclampsia, and growing evidence suggests a role for the gut microbiome in the development of preeclampsia. However, neither alterations in the gut microbiome associated with preeclampsia nor the mechanisms involved are fully understood. In this study, we tested the hypothesis that normal gestational maternal gut microbiome remodeling is impaired in the Dahl salt-sensitive (Dahl S) rat model of superimposed preeclampsia. Gut microbiome profiles of pregnant Dahl S, normal pregnant Sprague-Dawley (SD), and matched virgin controls were assessed by 16S rRNA gene sequencing at baseline; during early, middle, and late pregnancy; and 1-wk postpartum. Dahl S rats had significantly higher abundance in Proteobacteria, and multiple genera were significantly different from SD rats at baseline. The pregnant SD displayed a significant increase in Proteobacteria and genera such as Helicobacter, but these were not different between pregnant and virgin Dahl S rats. By late pregnancy, Dahl S rats had significantly lower α-diversity and Firmicutes compared with their virgin Dahl S controls. ß-diversity was significantly different among groups (P < 0.001). KEGG metabolic pathways including those associated with short-chain fatty acids were different in Dahl S pregnancy but not in SD pregnancy. These results reveal an association between chronic hypertension and gut microbiome dysbiosis which may hinder pregnancy-specific remodeling in the gut microbial composition during superimposed preeclampsia.


Assuntos
Modelos Animais de Doenças , Microbioma Gastrointestinal/fisiologia , Hipertensão/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Animais , Bactérias/classificação , Bactérias/genética , Doença Crônica , Disbiose/genética , Disbiose/microbiologia , Disbiose/fisiopatologia , Feminino , Microbioma Gastrointestinal/genética , Variação Genética , Humanos , Filogenia , Gravidez , RNA Ribossômico 16S/genética , Ratos , Ratos Endogâmicos Dahl , Ratos Sprague-Dawley , Especificidade da Espécie
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