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1.
MMWR Morb Mortal Wkly Rep ; 73(13): 286-290, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573866

RESUMO

The Federal Retail Pharmacy Program (FRPP) facilitated integration of pharmacies as partners in national efforts to scale up vaccination capacity during the COVID-19 pandemic emergency response. To evaluate FRPP's contribution to vaccination efforts across various sociodemographic groups, data on COVID-19 bivalent mRNA vaccine doses administered during September 1, 2022-September 30, 2023, were evaluated from two sources: 1) FRPP data reported directly to CDC and 2) jurisdictional immunization information systems data reported to CDC from all 50 states, the District of Columbia, U.S. territories, and freely associated states. Among 59.8 million COVID-19 bivalent vaccine doses administered in the United States during this period, 40.5 million (67.7%) were administered by FRPP partners. The proportion of COVID-19 bivalent doses administered by FRPP partners ranged from 5.9% among children aged 6 months-4 years to 70.6% among adults aged 18-49 years. Among some racial and ethnic minority groups (e.g., Hispanic or Latino, non-Hispanic Black or African American, non-Hispanic Native Hawaiian or other Pacific Islander, and non-Hispanic Asian persons), ≥45% of COVID-19 bivalent vaccine doses were administered by FRPP partners. Further, in urban and rural areas, FRPP partners administered 81.6% and 60.0% of bivalent vaccine doses, respectively. The FRPP partnership administered approximately two thirds of all bivalent COVID-19 vaccine doses in the United States and provided vaccine access for persons across a wide range of sociodemographic groups, demonstrating that this program could serve as a model to address vaccination services needs for routine vaccines and to provide health services in other public health emergencies.


Assuntos
COVID-19 , Farmácia , Adulto , Criança , Humanos , Estados Unidos/epidemiologia , Etnicidade , Vacinas contra COVID-19 , Pandemias , COVID-19/epidemiologia , COVID-19/prevenção & controle , Grupos Minoritários , Vacinação , Vacinas Combinadas
2.
Vaccine ; 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38302337

RESUMO

To support efforts to vaccinate millions of Americans across the United States (US) against COVID-19, the US federal government (USG) launched the Pharmacy Partnership for Long-Term Care Program (PPP) in December 2020 and the Federal Retail Pharmacy Program (FRPP) in February 2021. These programs consisted of a collaborative partnership with the USG and 21 pharmacy organizations, including large retail chains, coordinating pharmacy services administrative organizations (PSAOs) representing independent retail and long-term care pharmacies, and pharmacy network administrators. These pharmacy organizations represented over 46,000 providers and created a robust channel for far-reaching COVID-19 vaccination across 56 state and local jurisdictions. PPP reported more than 8 million COVID-19 doses administered to residents and staff in long-term care facilities (LTCFs) as of June 2021. In addition, FRPP was responsible for administering more than 304 million doses, accounting for approximately 49% of all COVID-19 doses administered as of June 2023. This unprecedented public-private partnership allowed USG to rapidly adapt, expand, and aim to provide equitable access to vaccines for adults and eligible-aged children during the COVID-19 pandemic. As the largest federal COVID-19 vaccination program, the FRPP exemplifies how public-private partnerships can expand access to immunizations during a public health emergency. End-to-end informatics support helped pharmacies meet critical national public health goals and served as convenient access points for sustained health services. This manuscript describes lessons learned regarding informatics coordination with participating pharmacy partners to support the rapid and safe administration of COVID-19 vaccines across the US. The processes of onboarding to CDC's complex data network, establishing connections to state and local immunization information systems (IIS), and monitoring the quality of data pharmacy partners submitted to the CDC Data Clearinghouse (DCH) in alignment with the COVID-19 Vaccine Reporting Specifications (CVRS) are highlighted.

3.
Vaccine ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38360476

RESUMO

During December 2020 through May 2023, the Centers for Disease Control and Prevention's (CDC) Immunization Services Division supported and executed the largest vaccine distribution effort in U.S. history, delivering nearly one billion doses of COVID-19 vaccine to vaccine providers in all 50 states, District of Columbia, Puerto Rico, Virgin Islands, Guam, Federated States of Micronesia, American Samoa, Marshall Islands, Northern Mariana Islands, and Palau. While existing infrastructure, ordering, and distribution mechanisms were in place from the Vaccines for Children Program (VFC) and experience had been gained during the 2009 H1N1 pandemic and incorporated into influenza vaccination pandemic planning, the scale and complexity of the national mobilization against a novel coronavirus resulted in many previously unforeseen challenges, particularly related to transporting and storing the majority of the U.S. COVID-19 vaccine at frozen and ultra-cold temperatures. This article describes the infrastructure supporting the distribution of U.S. government-purchased COVID-19 vaccines that was in place pre-pandemic, and the infrastructure, processes, and communications efforts developed to support the heightened demands of the COVID-19 vaccination program, and describes lessons learned.

4.
Vaccine ; 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38097453

RESUMO

Immunizations are an important tool to reduce the burden of vaccine preventable diseases and improve population health.1 High-quality immunization data is essential to inform clinical and public health interventions and respond to outbreaks of vaccine-preventable diseases. To track COVID-19 vaccines and vaccinations, CDC established an integrated network that included vaccination provider systems, health information exchange systems, immunization information systems, pharmacy and dialysis systems, vaccine ordering systems, electronic health records, and tools to support mass vaccination clinics. All these systems reported data to CDC's COVID-19 response system (either directly or indirectly) where it was processed, analyzed, and disseminated. This unprecedented vaccine tracking effort provided essential information for public health officials that was used to monitor the COVID-19 response and guide decisions. This paper will describe systems, processes, and policies that enabled monitoring and reporting of COVID-19 vaccination efforts and share challenges and lessons learned for future public health emergency responses.

5.
Public Health Rep ; 138(6): 870-877, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37503697

RESUMO

To help achieve the initial goal of providing universal COVID-19 vaccine access to approximately 258 million adults in 62 US jurisdictions, the federal government launched the Federal Retail Pharmacy Program (FRPP) on February 11, 2021. We describe FRPP's collaboration among the federal government, US jurisdictions, federal entity partners, and 21 national chain and independent pharmacy networks to provide large-scale access to COVID-19 vaccines, particularly in communities disproportionately affected by COVID-19 (eg, people aged ≥65 years, people from racial and ethnic minority groups). FRPP initially provided 10 000 vaccination sites for people to access COVID-19 vaccines, which was increased to >35 000 vaccination sites by May 2021 and sustained through January 31, 2022. From February 11, 2021, through January 31, 2022, FRPP vaccination sites received 293 million doses and administered 219 million doses, representing 45% of all COVID-19 immunizations provided nationwide (38% of all first doses, 72% of all booster doses). This unprecedented public-private partnership allowed the federal government to rapidly adapt and scale up an equitable vaccination program to reach adults, later expanding access to vaccine-eligible children, during the COVID-19 pandemic. As the largest federal COVID-19 vaccination program, FRPP exemplifies how public-private partnerships can expand access to immunizations during a public health emergency. Pharmacies can help meet critical national public health goals by serving as convenient access points for sustained health services. Lessons learned from this effort-including the importance of strong coordination and communication, efficient reporting systems and data quality, and increasing access to and demand for vaccine, among others-may help improve future immunization programs and support health system resiliency, emphasizing community-level access and health equity during public health emergencies.

6.
Nurse Educ ; 48(6): E191-E195, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37000901

RESUMO

BACKGROUND: Telenursing is a growing field in health care but remains underutilized as a clinical learning opportunity in the prelicensure nursing curriculum. PROBLEM: Prelicensure nursing students need exposure to telenursing as an educational modality, which can serve as an alternative opportunity for clinical hours where facilities and resources are limited. APPROACH: Using standardized patients and a web-based videoconferencing platform, faculty developed an innovative, simulated telenursing encounter to expose nursing students to virtual patient care scenarios. The effectiveness of this learning experience was evaluated through student-teacher satisfaction debriefing and student performance on content-related examinations. OUTCOMES: Students scored higher on targeted examination questions than students from the same cohort who did not participate in the telenursing encounter. In addition, students voiced increased comfort and confidence with conducting patient interviews, providing patient education, and debriefing. CONCLUSION: Using a simulated telenursing encounter is useful in prelicensure nursing education by exposing students to patient interaction outside of traditional clinical settings and reinforcing essential nursing concepts.


Assuntos
Bacharelado em Enfermagem , Educação em Enfermagem , Estudantes de Enfermagem , Telenfermagem , Humanos , Pesquisa em Educação em Enfermagem , Aprendizagem , Currículo
7.
Clin Infect Dis ; 76(10): 1753-1760, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-36750643

RESUMO

BACKGROUND: Small sample sizes have limited prior studies' ability to capture severe COVID-19 outcomes, especially among Ad26.COV2.S vaccine recipients. This study of 18.9 million adults aged ≥18 years assessed relative vaccine effectiveness (rVE) in three recipient cohorts: (1) primary Ad26.COV2.S vaccine and Ad26.COV2.S booster (2 Ad26.COV2.S), (2) primary Ad26.COV2.S vaccine and mRNA booster (Ad26.COV2.S+mRNA), (3) two doses of primary mRNA vaccine and mRNA booster (3 mRNA). METHODS: We analyzed two de-identified datasets linked using privacy-preserving record linkage (PPRL): insurance claims and retail pharmacy COVID-19 vaccination data. We assessed the presence of COVID-19 diagnosis during January 1-March 31, 2022 in: (1) any claim, (2) outpatient claim, (3) emergency department (ED) claim, (4) inpatient claim, and (5) inpatient claim with intensive care unit (ICU) admission. rVE for each outcome comparing three recipient cohorts (reference: two Ad26.COV2.S doses) was estimated from adjusted Cox proportional hazards models. RESULTS: Compared with two Ad26.COV2.S doses, Ad26.COV2.S+mRNA and three mRNA doses were more effective against all COVID-19 outcomes, including 57% (95% CI: 52-62) and 62% (95% CI: 58-65) rVE against an ED visit; 44% (95% CI: 34-52) and 54% (95% CI: 48-59) rVE against hospitalization; and 48% (95% CI: 22-66) and 66% (95% CI: 53-75) rVE against ICU admission, respectively. CONCLUSIONS: This study demonstrated that Ad26.COV2.S + mRNA doses were as good as three doses of mRNA, and better than two doses of Ad26.COV2.S. Vaccination continues to be an important preventive measure for reducing the public health impact of COVID-19.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Humanos , Adolescente , COVID-19/epidemiologia , COVID-19/prevenção & controle , Ad26COVS1 , Teste para COVID-19 , Vacinas contra COVID-19 , Vacinação , RNA Mensageiro
8.
Infect Control Hosp Epidemiol ; 44(4): 638-642, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35993573

RESUMO

OBJECTIVE: To determine how engagement of the hospital and/or vendor with performance improvement strategies combined with an automated hand hygiene monitoring system (AHHMS) influence hand hygiene (HH) performance rates. DESIGN: Prospective, before-and-after, controlled observational study. SETTING: The study was conducted in 58 adult and pediatric inpatient units located in 10 hospitals. METHODS: HH performance rates were estimated using an AHHMS. Rates were expressed as the number of soap and alcohol-based hand rub portions dispensed divided by the number of room entries and exits. Each hospital self-assigned to one of the following intervention groups: AHHMS alone (control group), AHHMS plus clinician-based vendor support (vendor-only group), AHHMS plus hospital-led unit-based initiatives (hospital-only group), or AHHMS plus clinician-based vendor support and hospital-led unit-based initiatives (vendor-plus-hospital group). Each hospital unit produced 1­2 months of baseline HH performance data immediately after AHHMS installation before implementing initiatives. RESULTS: Hospital units in the vendor-plus-hospital group had a statistically significant increase of at least 46% in HH performance compared with units in the other 3 groups (P ≤ .006). Units in the hospital only group achieved a 1.3% increase in HH performance compared with units that had AHHMS alone (P = .950). Units with AHHMS plus other initiatives each had a larger change in HH performance rates over their baseline than those in the AHHMS-alone group (P < 0.001). CONCLUSIONS: AHHMS combined with clinician-based vendor support and hospital-led unit-based initiatives resulted in the greatest improvements in HH performance. These results illustrate the value of a collaborative partnership between the hospital and the AHHMS vendor.


Assuntos
Infecção Hospitalar , Higiene das Mãos , Adulto , Criança , Humanos , Higiene das Mãos/métodos , Estudos Prospectivos , Unidades Hospitalares , Etanol
9.
Sensors (Basel) ; 22(8)2022 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-35458893

RESUMO

The Radiation and Dust Sensor is one of six sensors of the Mars Environmental Dynamics Analyzer onboard the Perseverance rover from the Mars 2020 NASA mission. Its primary goal is to characterize the airbone dust in the Mars atmosphere, inferring its concentration, shape and optical properties. Thanks to its geometry, the sensor will be capable of studying dust-lifting processes with a high temporal resolution and high spatial coverage. Thanks to its multiwavelength design, it will characterize the solar spectrum from Mars' surface. The present work describes the sensor design from the scientific and technical requirements, the qualification processes to demonstrate its endurance on Mars' surface, the calibration activities to demonstrate its performance, and its validation campaign in a representative Mars analog. As a result of this process, we obtained a very compact sensor, fully digital, with a mass below 1 kg and exceptional power consumption and data budget features.


Assuntos
Poeira , Meio Ambiente Extraterreno , Atmosfera
10.
J Am Assoc Nurse Pract ; 34(3): 537-541, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34678808

RESUMO

ABSTRACT: The educational preparation of nurse practitioner (NP) students includes didactic content and clinical experiences. These clinical experiences can be via clinical rotations or simulation. Although there is no specific list of clinical skills to prepare NP students for professional practice, the National Organization for Nurse Practitioner Faculties identifies core competencies for the basic education of NP students. These core competencies can be fulfilled through simulated clinical experiences. However, due to the COVID-19 pandemic, many institutions had to develop alternate methods of facilitating simulated clinical experiences for their NP students. Because of national, state, and university guidelines to transition all face-to-face educational activities to a virtual format, a Southeastern university simulation program developed and implemented virtual clinical skills experiences for psychiatric mental health NP students. Based on student survey results, the utilization of standardized patients in this virtual clinical skills experience proved beneficial and improved NP students' interviewing and communication skills via a telehealth format.

11.
Kidney Int Rep ; 6(7): 1764-1774, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34307973

RESUMO

A healthy eating pattern has proven to lower the risk of metabolic and cardiovascular diseases. However, there are sparse dietary recommendations for kidney transplant recipients, and the ones available focus only on single nutrients intake, such as sodium, potassium, and proteins, and not on the overall eating pattern. Considering that individuals do not typically consume nutrients in isolation, but as part of a complete dietary pattern, it is challenging for the average transplanted patient to understand and implement specific dietary recommendations. Also, single-nutrient interventions demonstrate largely inconclusive effects, and it seems improbable that they could have a strong enough impact on transplant outcomes. Dietary trends such as plant-based diets, intermittent fasting, low-carb diet/keto-diet, and juicing, have gained major attention from the media. Herein, we review the potential risks and benefits of these diets in kidney transplant recipients and provide an updated dietary recommendation for this population with consideration of current nutritional trends. Overall, the Mediterranean and DASH diets have demonstrated to be the most beneficial dietary patterns to the post kidney transplant population by focusing on less meat and processed foods, while increasing the intake of fresh foods and plant-based choices. We believe that to maintain a healthy lifestyle posttransplant, patients should be educated about the scientific evidence of different diets and choose a dietary pattern that is sustainable long-term.

13.
Curr Med Res Opin ; 37(5): 743-751, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33648384

RESUMO

Objective: The objective of this study was to describe the pattern of comorbidities in patients with type 2 diabetes mellitus with and without atherosclerotic cardiovascular disease.Methods: This was a retrospective, cross-sectional analysis of the IQVIA Commercial Data Delivery database. Patients were ≥18 years on their last encounter between 1 October 2014 and 30 September 2015 and had either a type 2 diabetes mellitus diagnosis or a prescription for an oral diabetes medication. Atherosclerotic cardiovascular disease was confirmed by diagnosis codes. Comorbidities were identified using diagnosis codes, clinical measurements, and/or medication use.Results: A total of 1,522,526 type 2 diabetes mellitus patients were included in the analysis, 25% of whom had atherosclerotic cardiovascular disease. The most common comorbidities were hypertension, hyperlipidemia, overweight/obesity, chronic kidney disease, congestive heart failure, and neuropathy. These were present, respectively, in the following percentages of patients with and without cardiovascular disease: 98.3 and 91.0%, 94.8 and 78.5%, 80.5 and 80.6%, 38.5 and 18.9, 20.2, and 4.3%, and 13.7 and 8.6%. Thus, the frequencies of hyperlipidemia, chronic kidney disease, and congestive heart failure were notably higher in patients with cardiovascular disease. This trend held true for patients grouped by sex, age, and race.Conclusions: Patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease have different rates of certain comorbidities compared to those without atherosclerotic cardiovascular disease.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Doenças Cardiovasculares/epidemiologia , Comorbidade , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Estudos Retrospectivos
14.
Am J Infect Control ; 49(1): 30-33, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32818577

RESUMO

BACKGROUND: Achieving high levels of hand hygiene compliance of health care personnel has been an ongoing challenge. The objective of this study was to examine the impact of the COVID-19 pandemic on hand hygiene performance (HHP) rates in acute care hospitals. METHODS: HHP rates were estimated using an automated hand hygiene monitoring system installed in 74 adult inpatient units in 7 hospitals and 10 pediatric inpatient units in 2 children's hospitals. A segmented regression model was used to estimate the trajectory of HHP rates in the 10 weeks leading up to a COVID-19-related milestone event (eg, school closures) and for 10 weeks after. RESULTS: Three effects emerged, all of which were significant at P < .01. Average HHP rates increased from 46% to 56% in the months preceding pandemic-related school closures. This was followed by a 6% upward shift at the time school closures occurred. HHP rates remained over 60% for 4 weeks before declining to 54% at the end of the study period. CONCLUSIONS: Data from an automated hand hygiene monitoring system indicated that HHP shifted in multiple directions during the early stages of the pandemic. We discuss possible reasons why HHP first increased as the pandemic began and then decreased as it progressed.


Assuntos
COVID-19/epidemiologia , Fidelidade a Diretrizes/tendências , Desinfecção das Mãos/tendências , Pessoal de Saúde , Controle de Infecções/tendências , Automação , COVID-19/prevenção & controle , Desinfecção das Mãos/normas , Higiene das Mãos/normas , Higiene das Mãos/tendências , Higienizadores de Mão , Hospitais , Humanos , Controle de Infecções/normas , SARS-CoV-2 , Sabões , Estados Unidos/epidemiologia
15.
Am J Infect Control ; 47(5): 585-587, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30528169

RESUMO

The objective of this study is to determine what percentage of patient room entries and exits (opportunities) are attributed to health care personnel (HCP) and non-HCP. A total of 14,876 opportunities were observed by clinicians in 29 units of 16 hospitals. HCP accounted for 83.6%; 95% confidence interval, 81.3%-87.6%. This finding provides hospitals an initial baseline for HCP room traffic when implementing community-based automated hand hygiene monitoring and compliance improvement efforts.


Assuntos
Pessoal de Saúde/normas , Quartos de Pacientes/normas , Cuidados Críticos/normas , Infecção Hospitalar/prevenção & controle , Fidelidade a Diretrizes/normas , Higiene das Mãos/normas , Humanos , Controle de Infecções/normas
16.
Nutr Health ; 24(4): 251-259, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30231801

RESUMO

BACKGROUND: Consumption of added sugars (AS) and sugar-sweetened beverages (SSB) may adversely affect adolescents' weight and cardiovascular disease risk. Reliance on self-reported dietary assessment methods is a common research limitation, which could be overcome by dietary intake biomarkers. AIM: The investigation was a proof-of-concept study to evaluate the proposed carbon isotope ratio (δ13C) biomarker of AS intake in adolescents, using a controlled feeding design. METHODS: Participants (n = 33, age 15.3 years, 53% female) underwent two seven-day controlled feeding periods in a randomly assigned order. Diets were matched in composition except for AS content (5% or 25% of total energy). Fasting fingerstick blood samples were collected daily during each diet period. RESULTS: Fingerstick δ13C values changed from day 1 to 8 by -0.05 ± 0.071‰ on 5% AS, and +0.03 ± 0.083‰ on 25% AS (p ≤ 0.001). Reliability was demonstrated between day 7 and 8 δ13C values on the 5% (ICC = 0.996, p ≤ 0.001) and 25% (ICC = 0.997, p ≤ 0.001) AS diets. CONCLUSIONS: Larger scale investigations are warranted to determine if this technique could be applied to population-level research in order to help assess the effectiveness of interventions aimed at reducing the consumption of AS or SSB intake.


Assuntos
Isótopos de Carbono/sangue , Dieta/métodos , Açúcares da Dieta/sangue , Açúcares da Dieta/farmacologia , Adolescente , Biomarcadores/sangue , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Tempo
17.
Eat Behav ; 30: 9-15, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29751193

RESUMO

BACKGROUND: High added sugar (AS) intake is associated with obesity and poor diet quality. Guidelines recommended limiting AS to 5-10% of total energy intake, but palatability and feasibility of this AS intake level is uncertain. OBJECTIVE: To compare adolescents' perceptions of hunger, fullness, and palatability in response to a low AS adequate fiber (LASAF; 5% total energy from AS and 13.5 g fiber/1000 kcal) and a high AS low fiber (HASLF; 25% total energy form AS and 8.2 g/1000 kcal) diet. DESIGN: Adolescents (n = 32, age: 15.3 ±â€¯1.6 yrs., BMI percentile: 47 ±â€¯4, 15 male) completed a randomized, crossover, controlled feeding study. Participants consumed calorie-matched LASAF and HASLF diets for 7 days, separated by a 4 week washout. Body weight was monitored daily on each diet. Hunger, fullness, and palatability were assessed via 100 mm visual analogue scales at the end of each feeding period. Differences were assessed with paired sample t-tests. Data are expressed as mean ±â€¯SD. RESULTS: Participants remained weight stable, and no difference in weight change between diet conditions was detected (LASAF: -0.06 ±â€¯0.7 vs. HASLF: -0.02 ±â€¯0.6 kg, p = 0.751). Less hunger (LASAF: 24.1 ±â€¯14.6 vs. HASLF: 32.1 ±â€¯17.6 mm, p = 0.024) and greater fullness (LASAF: 70.2 ±â€¯12.3 vs. HASLF: 61.3 ±â€¯18.1 mm, p = 0.006) were reported on the LASAF compared to the HASLF. Participants reported the diets to be equally palatable (LASAF: 39.6 ±â€¯12.9 vs. HASLF: 37.2 ±â€¯17.8 mm, p = 0.440). CONCLUSIONS: Adolescents perceive a LASAF diet to be as palatable as a HASLF diet, but more satiating. LASAF diets should be investigated as a strategy for weight control in adolescents.


Assuntos
Dieta/psicologia , Fibras na Dieta/administração & dosagem , Açúcares da Dieta/administração & dosagem , Saciação , Adolescente , Estudos Cross-Over , Dieta/estatística & dados numéricos , Feminino , Humanos , Masculino , Projetos Piloto
18.
J Ocul Pharmacol Ther ; 34(1-2): 40-51, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28609185

RESUMO

PURPOSE: Rho-associated protein kinase (ROCK) inhibitors lower intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM). The preclinical characterization of netarsudil, a new ROCK/norepinephrine transporter (NET) inhibitor currently in clinical development, is presented herein. METHODS: The kinase inhibitory activity of netarsudil was compared to its esterase metabolite, netarsudil-M1, and 3 other ROCK inhibitors using a commercially available kinase assay kit. Disruption of actin stress fibers was measured in primary porcine TM cells and disruption of focal adhesions in transformed human TM (HTM) cells. Induction of fibrosis markers after exposure to transforming growth factor-ß2 (TGF-ß2) was conducted in primary HTM cells. Ocular hypotensive activity and tolerability of topical formulations were evaluated in normotensive Dutch Belted rabbits and Formosan Rock monkeys. In vitro corneal metabolism assays were conducted using dog, pig, rabbit, monkey, and human corneas. In vivo ocular pharmacokinetics was studied in Dutch Belted rabbits. RESULTS: Netarsudil inhibited kinases ROCK1 and ROCK2 with a Ki of 1 nM each, disrupted actin stress fibers and focal adhesions in TM cells with IC50s of 79 and 16 nM, respectively, and blocked the profibrotic effects of TGF-ß2 in HTM cells. Netarsudil produced large reductions in IOP in rabbits and monkeys that were sustained for at least 24 h after once daily dosing, with transient, mild hyperemia observed as the only adverse effect. CONCLUSION: Netarsudil is a novel ROCK/NET inhibitor with high potency in biochemical and cell-based assays, an ability to produce large and durable IOP reductions in animal models, and favorable pharmacokinetic and ocular tolerability profiles.


Assuntos
Anti-Hipertensivos/uso terapêutico , Benzoatos/farmacologia , Descoberta de Drogas , Hipertensão Ocular/tratamento farmacológico , Soluções Oftálmicas/uso terapêutico , beta-Alanina/análogos & derivados , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/química , Benzoatos/administração & dosagem , Benzoatos/química , Modelos Animais de Doenças , Cães , Tolerância a Medicamentos , Haplorrinos , Humanos , Masculino , Estrutura Molecular , Hipertensão Ocular/patologia , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/química , Coelhos , Suínos , beta-Alanina/administração & dosagem , beta-Alanina/química , beta-Alanina/farmacologia
19.
J Nutr ; 147(12): 2364-2373, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28931586

RESUMO

Background: Objective indicators of dietary intake (e.g., biomarkers) are needed to overcome the limitations of self-reported dietary intake assessment methods in adolescents. To our knowledge, no controlled feeding studies to date have evaluated the validity of urinary sodium, nitrogen, or sugar excretion as dietary biomarkers in adolescents.Objective: This investigation aimed to evaluate the validity of urinary sodium, nitrogen, and total sugars (TS) excretion as biomarkers for sodium, protein, and added sugars (AS) intake in nonobese adolescents.Methods: In a crossover controlled feeding study design, 33 adolescents [12-18 y of age, 47 ± 25th percentile (mean ± SD) of body mass index (BMI; in kg/m2) for age] consumed 5% AS [low added sugars (LAS)] and 25% AS [high added sugars (HAS)] isocaloric, macronutrient-matched (55% carbohydrate, 30% fat, and 15% protein) diets for 7 d each, in a randomly assigned order, with a 4-wk washout period between diets. On the final 2 d of each diet period, 24-h urine samples were collected. Thirty-two adolescents completed all measurements (97% retention).Results: Urinary sodium was not different from the expected 90% recovery (mean ± SD: 88% ± 18%, P = 0.50). Urinary nitrogen was correlated with protein intake (r = 0.69, P < 0.001), although it was below the 80% expected recovery (62% ± 7%, P < 0.001). Urinary TS values were correlated with AS intake during the HAS diet (r = 0.77, P < 0.001) and had a higher R2 value of 0.28 than did AS intake (R2 = 0.36). TS excretion differed between LAS (0.226 ± 0.09 mg/d) and HAS (0.365 ± 0.16 mg/d) feeding periods (P < 0.001).Conclusions: Urinary sodium appears to be a valid biomarker for sodium intake in nonobese adolescents. Urinary nitrogen is associated with protein intake, but nitrogen excretion rates were less than previously reported for adults, possibly owing to adolescent growth rates. TS excretion reflects AS at 25% AS intake and was responsive to the change in AS intake. Thus, urinary biomarkers are promising objective indicators of dietary intake in adolescents, although larger-scale feeding trials are needed to confirm these findings. This trial was registered at clinicaltrials.gov as NCT02455388.


Assuntos
Carboidratos/urina , Carboidratos da Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Nitrogênio/urina , Sódio na Dieta/administração & dosagem , Sódio/urina , Adolescente , Biomarcadores , Criança , Estudos Cross-Over , Feminino , Humanos , Masculino
20.
Bioorg Med Chem Lett ; 26(10): 2475-2480, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-27072905

RESUMO

Inhibition of Rho kinase (ROCK) to improve fluid outflow through the trabecular meshwork and lower intraocular pressure is a strategy for the development of new anti-glaucoma agents. Alpha-aryl-beta-amino isoquinoline analogs were identified as potent ROCK inhibitors. Compounds that provided a longer duration of intraocular pressure reduction in Dutch Belted rabbits also inhibited norepinephrine transporter. Ester 60 improved bioavailability of its parent ROCK inhibitor, 29 (Ki=0.2nM) and demonstrated an effective and sustained IOP reduction for 24h after dosing. From these studies, netarsudil (a.k.a. AR-13324) was discovered and is currently in clinical trials for the treatment of glaucoma and ocular hypertension.


Assuntos
Benzoatos/farmacologia , Glaucoma de Ângulo Aberto/tratamento farmacológico , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , beta-Alanina/análogos & derivados , Quinases Associadas a rho/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Pressão Intraocular/efeitos dos fármacos , Estrutura Molecular , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/antagonistas & inibidores , Inibidores de Proteínas Quinases/síntese química , Coelhos , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Relação Estrutura-Atividade , Malha Trabecular/efeitos dos fármacos , beta-Alanina/farmacologia
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