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1.
Br J Clin Pharmacol ; 89(7): 2190-2200, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36740580

RESUMO

AIM: SWORD-1 and SWORD-2 phase 3 studies concluded that switching virologically suppressed participants with HIV-1 from their current three- or four-drug antiretroviral regimen (CAR) to the two-drug regimen of once-daily dolutegravir (DTG, 50 mg) and rilpivirine (RPV, 25 mg) was safe, well tolerated and noninferior for maintaining HIV-1 suppression at week 48 and highly efficacious to week 148. A secondary objective was to characterize drug exposure and exposure-efficacy/safety relationships. METHODS: Adults with plasma HIV-1 RNA <50 copies/mL were randomized to switch to once-daily DTG + RPV on day 1 or to continue CAR for 52 weeks before switching. Trough plasma concentrations (C0) of DTG and RPV, the proportion of participants with HIV-1 RNA <50 copies/mL and adverse events to week 100 were summarized and subjected to exposure-response analyses in the overall population, in the subset of participants who switched from CAR containing enzyme-inducing drugs and by age category (≥50 and <50 years). The relationship between C0avg (individual average C0 across visits) and efficacy/safety was investigated. RESULTS: Although week 2 DTG and RPV C0 were lower in participants switching from enzyme-inducing antiretroviral drugs, C0 and C0avg stayed above in vitro antiviral protein binding-adjusted IC90 and to week 100 with viral suppression >89%. DTG or RPV C0avg showed no relationship with virologic failures or safety. Participants ≥50 years had similar C0avg and safety response to younger participants. CONCLUSION: No clinically relevant relationship between DTG or RPV exposures and virologic or safety response was observed, confirming the DTG + RPV switch for participants as a safe and effective treatment.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adulto , Humanos , Pessoa de Meia-Idade , Infecções por HIV/tratamento farmacológico , Rilpivirina/efeitos adversos , Oxazinas , Piridonas/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Antirretrovirais/uso terapêutico , Resultado do Tratamento , RNA , Carga Viral
2.
Fam Community Health ; 46(3): 181-191, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37083718

RESUMO

Greenspace positively impacts mental health. Previous research has focused on the greenspace-mental health relationship in urban areas. Yet, little work has looked at rural areas despite rural communities reporting similar rates of poor mental health outcomes and higher rates of suicide mortality compared with urban areas. This ecological research study examined the following research questions: (1) Do public and/or private greenspaces affect the spatial distribution of mental health outcomes in North Carolina? (2) Does this relationship change with rurality? Emergency department data for 6 mental health conditions and suicide mortality data from 2009 to 2018 were included in this analysis. Spatial error and ordinary least squares regressions were used to examine the influence of public and private greenspace quantity on mental health in rural and urban communities. Results suggest greenspace benefits mental health in rural and urban communities. The strength of this relationship varies with urbanity and between public and private greenspaces, suggesting a more complex causal relationship. Given the high case counts and often lower density of mental health care facilities in rural areas, focusing attention on low-cost mental health interventions, such as greenspace, is important when considering rural mental health care.


Assuntos
Saúde Mental , População Rural , Humanos , Parques Recreativos , North Carolina/epidemiologia , Análise Espacial
3.
Dev Psychopathol ; 33(2): 493-505, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33955344

RESUMO

Over 50% of adoptions are transracial, involving primarily White parents and children of color from different ethnic or racial backgrounds. Transracial adoptive (TRA) parents are tasked with providing ethnic-racial socialization processes (ERS) to support TRA adoptees' ethnic-racial identity development and prepare them to cope with ethnic-racial discrimination. However, unlike nonadoptive families of color, TRA parents lack shared cultural history with adoptees and have limited experience navigating racial discrimination. Knowledge of ERS among TRA families has centered on unidirectional processes between parenting constructs, ERS processes, and children's functioning. However, ERS processes in this population have complexities and nuances that warrant more sensitive and robust conceptualization. This paper proposes a process-oriented dynamic ecological model of the system of ERS, situating transacting processes in and across multiple family levels (parent, adoptee, family) and incorporating developmental and contextual considerations. With its framing of the complexities in ERS among TRA families, the model offers three contributions: a conceptual organization of parenting constructs related to ERS, a more robust understanding of ERS processes that inform how parents provide ERS, and framing of transacting processes within and between parenting constructs, ERS processes, and children's functioning. Implications for research, policy, and practice are discussed.


Assuntos
Adoção , Socialização , Criança , Etnicidade , Humanos , Poder Familiar , Grupos Raciais
4.
Cochrane Database Syst Rev ; 7: CD013067, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31335963

RESUMO

BACKGROUND: Cough both protects and clears the airway. Cough has three phases: breathing in (inspiration), closure of the glottis, and a forced expiratory effort. Chronic cough has a negative, far-reaching impact on quality of life. Few effective medical treatments for individuals with unexplained (idiopathic/refractory) chronic cough (UCC) are known. For this group, current guidelines advocate the use of gabapentin. Speech and language therapy (SLT) has been considered as a non-pharmacological option for managing UCC without the risks and side effects associated with pharmacological agents, and this review considers the evidence from randomised controlled trials (RCTs) evaluating the effectiveness of SLT in this context. OBJECTIVES: To evaluate the effectiveness of speech and language therapy for treatment of people with unexplained (idiopathic/refractory) chronic cough. SEARCH METHODS: We searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, trials registries, and reference lists of included studies. Our most recent search was 8 February 2019. SELECTION CRITERIA: We included RCTs in which participants had a diagnosis of UCC having undergone a full diagnostic workup to exclude an underlying cause, as per published guidelines or local protocols, and where the intervention included speech and language therapy techniques for UCC. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of 94 records. Two clinical trials, represented in 10 study reports, met our predefined inclusion criteria. Two review authors independently assessed risk of bias for each study and extracted outcome data. We analysed dichotomous data as odds ratios (ORs), and continuous data as mean differences (MDs) or geometric mean differences. We used standard methods recommended by Cochrane. Our primary outcomes were health-related quality of life (HRQoL) and serious adverse events (SAEs). MAIN RESULTS: We found two studies involving 162 adults that met our inclusion criteria. Neither of the two studies included children. The duration of treatment and length of sessions varied between studies from four sessions delivered weekly, to four sessions over two months. Similarly, length of sessions varied slightly from one 60-minute session and three 45-minute sessions to four 30-minute sessions. The control interventions were healthy lifestyle advice in both studies.One study contributed HRQoL data, using the Leicester Cough Questionnaire (LCQ), and we judged the quality of the evidence to be low using the GRADE approach. Data were reported as between-group difference from baseline to four weeks (MD 1.53, 95% confidence interval (CI) 0.21 to 2.85; participants = 71), revealing a statistically significant benefit for people receiving a physiotherapy and speech and language therapy intervention (PSALTI) versus control. However, the difference between PSALTI and control was not observed between week four and three months. The same study provided information on SAEs, and there were no SAEs in either the PSALTI or control arms. Using the GRADE approach we judged the quality of evidence for this outcome to be low.Data were also available for our prespecified secondary outcomes. In each case data were provided by only one study, therefore there were no opportunities for aggregation; we judged the quality of this evidence to be low for each outcome. A significant difference favouring therapy was demonstrated for: objective cough counts (ratio for mean coughs per hour on treatment was 59% (95% CI 37% to 95%) relative to control; participants = 71); symptom score (MD 9.80, 95% CI 4.50 to 15.10; participants = 87); and clinical improvement as defined by trialists (OR 48.13, 95% CI 13.53 to 171.25; participants = 87). There was no significant difference between therapy and control regarding subjective measures of cough (MD on visual analogue scale of cough severity: -9.72, 95% CI -20.80 to 1.36; participants = 71) and cough reflex sensitivity (capsaicin concentration to induce five coughs: 1.11 (95% CI 0.80 to 1.54; participants = 49) times higher on treatment than on control). One study reported data on adverse events, and there were no adverse events reported in either the therapy or control arms of the study. AUTHORS' CONCLUSIONS: The paucity of data in this review highlights the need for more controlled trial data examining the efficacy of SLT interventions in the management of UCC. Although a large number of studies were found in the initial search as per protocol, we could include only two studies in the review. In addition, this review highlights that endpoints vary between published studies.The improvements in HRQoL (LCQ) and reduction in 24-hour cough frequency seen with the PSALTI intervention were statistically significant but short-lived, with the between-group difference lasting up to four weeks only. Further studies are required to replicate these findings and to investigate the effects of SLT interventions over time. It is clear that SLT interventions vary between studies. Further research is needed to understand which aspects of SLT interventions are most effective in reducing cough (both objective cough frequency and subjective measures of cough) and improving HRQoL. We consider these endpoints to be clinically important. It is also important for future studies to report information on adverse events.Because of the paucity of data, we can draw no robust conclusions regarding the efficacy of SLT interventions for improving outcomes in unexplained chronic cough. Our review identifies the need for further high-quality research, with comparable endpoints to inform robust conclusions.


Assuntos
Tosse/terapia , Terapia da Linguagem , Fonoterapia , Doença Crônica , Humanos , Modalidades de Fisioterapia , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Mayo Clin Proc Innov Qual Outcomes ; 8(3): 263-275, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38807973

RESUMO

Behavior change is the foundation for effective lifestyle prescriptions, yet such change is individualized, nonlinear and typically requires ongoing support. Health and wellness coaching (HWC) is a behavior change intervention with rapidly accruing evidence of positive impact on health behaviors such as exercise, nutrition and stress management. Furthermore, HWC enhances prevention and mitigates exacerbation of chronic lifestyle diseases, at least in the short-term (up to 6 months post intervention). Although the impact on long-term stability of behavior change remains unclear, it is evident that effective partnering with patients using key communication strategies, autonomy promotion, and flexible permissiveness can empower patients to develop healthy lifestyles. This partnership can be cultivated by clinicians as well as clinical team members including nationally board-certified coaches. Although much research is needed regarding the ongoing maintenance of lifestyle changes beyond 6 months, this article seeks to equip clinicians with current evidence, theoretical insights and practical strategies from a "coach approach" to foster more intrinsic forms of motivation which, in turn, empowers patients to adopt and maintain health-promoting behaviors.

6.
Open Forum Infect Dis ; 10(3): ofad101, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36968959

RESUMO

Background: We assessed the efficacy and safety of dolutegravir/lamivudine (DTG/3TC) in a US test-and-treat setting at a secondary 48-week time point of the multicenter, single-arm, phase IIIb STAT study. Methods: Participants were eligible adults newly diagnosed with human immunodeficiency virus (HIV)-1 and had started once-daily DTG/3TC within 14 days of diagnosis, before laboratory results were available. Antiretroviral therapy (ART) was modified if baseline testing indicated DTG or 3TC resistance, hepatitis B virus (HBV) coinfection, or creatinine clearance <30 mL/min per 1.73 m2, and these participants remained in the study. A proportion with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48 was calculated among all participants (intention-to-treat-exposed [ITT-E] missing = failure analysis) and those with available data (observed analysis). Results: At Week 48, 82% of all participants regardless of ART (107 of 131; ITT-E missing = failure) and 97% with available data (107 of 110; observed analysis) achieved HIV-1 RNA <50 copies/mL. High proportions of virologic response were seen overall, including in participants with high viral load (≥500 000 copies/mL; 89%) or low CD4+ cell count (<200 cells/mm3; 78%) at baseline. Ten participants had treatment modification (baseline HBV coinfection, n = 5; participant/proxy decision, n = 2; baseline M184V resistance mutation, adverse event [AE; rash], and pregnancy, n = 1 each) before Week 48. Two participants met confirmed virologic failure criteria. No treatment-emergent resistance was observed. Ten participants reported drug-related AEs (all grade 1-2); no serious drug-related AEs occurred. Conclusions: Results demonstrated high proportions of participants with sustained virologic suppression, no treatment-emergent resistance, and good safety over 48 weeks, supporting first-line use of DTG/3TC in a test-and-treat setting.

7.
Sci Total Environ ; 808: 152145, 2022 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-34871679

RESUMO

Greenspace may positively impact pregnancy health for racially and economically minoritized populations; few studies have examined local availability and accessibility of green/park space in reducing maternal morbidity. The objective of this retrospective birth cohort study was to examine the association between residential exposure to greenspace and adverse pregnancy health outcomes in a Southern US state characterized by high poverty and racial disparities in maternal health (2013-2017). National data from the Protected Area database - United States (PAD-US) and ParkServe estimated three publicly available and accessible residential greenspace measures-a more direct proxy than using remotely-sensed greenness indicators (e.g., normalized difference vegetation index (NDVI))-(a) percent area of greenspace (M1), (b) area of available greenspace per person (M2), (c) total population within a 10-minute walk (M3). Generalized Estimating Equations with logistic regression were used to examine the association between individual greenspace metrics and South Carolina hospital deliveries (n = 238,922 deliveries) for women with correlated maternal health outcomes for gestational hypertension (GHTN), gestational diabetes (GD), severe maternal morbidity (SMM), preeclampsia (PRE), mental disorders (MD), depressive disorders (DD), and preterm birth (PTB). Lowest compared to highest tertiles of all three metrics were associated with increased risk for MD, DD, and a monotonic increase in GD, particularly for black women. Women with the lowest access to M2 and M3 were more at risk for PRE, PTB, and MD. We observed that women in low-income, majority-black communities in the lowest versus highest tertile of M2 were more likely to experience a DD, MD, SMM, or PTB compared to primarily high-income majority-white communities. Available and accessible green/park space may present as an effective nature-based intervention to reduce maternal complications, particularly for gestational diabetes and other pregnancy health risks for which there are currently few known evidence-based primary prevention strategies.


Assuntos
Disparidades nos Níveis de Saúde , Complicações na Gravidez , Nascimento Prematuro , Coorte de Nascimento , Etnicidade , Feminino , Humanos , Recém-Nascido , Parques Recreativos , Gravidez , Grupos Raciais , Estudos Retrospectivos , Estados Unidos
8.
ISME J ; 16(3): 812-821, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34628478

RESUMO

The efficacy of antibiotic treatments targeting polymicrobial communities is not well predicted by conventional in vitro susceptibility testing based on determining minimum inhibitory concentration (MIC) in monocultures. One reason for this is that inter-species interactions can alter the community members' susceptibility to antibiotics. Here we quantify, and identify mechanisms for, community-modulated changes of efficacy for clinically relevant antibiotics against the pathogen Pseudomonas aeruginosa in model cystic fibrosis (CF) lung communities derived from clinical samples. We demonstrate that multi-drug resistant Stenotrophomonas maltophilia can provide high levels of antibiotic protection to otherwise sensitive P. aeruginosa. Exposure protection to imipenem was provided by chromosomally encoded metallo-ß-lactamase that detoxified the environment; protection was dependent upon S. maltophilia cell density and was provided by S. maltophilia strains isolated from CF sputum, increasing the MIC of P. aeruginosa by up to 16-fold. In contrast, the presence of S. maltophilia provided no protection against meropenem, another routinely used carbapenem. Mathematical ordinary differential equation modelling shows that the level of exposure protection provided against different carbapenems can be explained by differences in antibiotic efficacy and inactivation rate. Together, these findings reveal that exploitation of pre-occurring antimicrobial resistance, and inter-specific competition, can have large impacts on pathogen antibiotic susceptibility, highlighting the importance of microbial ecology for designing successful antibiotic treatments for multispecies communities.


Assuntos
Antibacterianos , Fibrose Cística , Antibacterianos/farmacologia , Fibrose Cística/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/genética , beta-Lactamases/genética
9.
J Acquir Immune Defic Syndr ; 91(1): 73-78, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35551149

RESUMO

BACKGROUND: Switching to the 2-drug regimen dolutegravir + rilpivirine demonstrated noninferiority vs continuing a 3-drug or 4-drug current antiretroviral regimen (CAR) at week 48 and maintained high levels of virologic suppression to week 148 in the SWORD studies. We report inflammation and atherogenesis biomarkers postswitch to dolutegravir + rilpivirine. SETTING: SWORD-1: 65 centers, 13 countries; SWORD-2: 60 centers, 11 countries. METHODS: Virologically suppressed adults were randomized to switch to dolutegravir + rilpivirine (early-switch group; n = 513) or continue CAR (n = 511). Participants continuing CAR switched to dolutegravir + rilpivirine at week 52 (late-switch group; n = 477). Biomarkers were evaluated from Baseline to week 48 for dolutegravir + rilpivirine and CAR and noncomparatively for dolutegravir + rilpivirine postswitch through 148 weeks (early-switch) and 96 weeks (late-switch). RESULTS: Through week 48, changes in biomarkers did not significantly differ between dolutegravir + rilpivirine and CAR groups, except for increases in soluble CD14 and decreases in fatty acid-binding protein-2, which favored dolutegravir + rilpivirine. For inflammation biomarkers through week 148, there was no marked change in C-reactive protein, inconsistent changes in soluble CD14 and interleukin-6, and increases in soluble CD163. For atherogenesis biomarkers through week 148, fatty acid-binding protein-2 and soluble vascular cell adhesion molecule-1 showed sustained reductions; D-dimer showed inconsistent increases between early-switch vs late-switch groups. CONCLUSIONS: No consistent pattern of change in biomarkers postswitch to dolutegravir + rilpivirine was observed through weeks 48 and 148 in SWORD-1/SWORD-2, suggesting no association of increased inflammation or atherogenesis with the 2-drug regimen while maintaining virologic suppression.


Assuntos
Fármacos Anti-HIV , Aterosclerose , Infecções por HIV , Adulto , Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/uso terapêutico , Aterosclerose/induzido quimicamente , Proteínas de Ligação a Ácido Graxo/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Inflamação/tratamento farmacológico , Receptores de Lipopolissacarídeos , Oxazinas/uso terapêutico , Piperazinas , Piridonas/uso terapêutico , Rilpivirina/uso terapêutico , Carga Viral
10.
AIDS ; 35(12): 1957-1965, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34115650

RESUMO

OBJECTIVES: Dolutegravir/lamivudine (DTG/3TC) is indicated for treatment-naive and experienced people with HIV; however, questions remain about its utility in a test-and-treat setting because of potential transmitted resistance and baseline hepatitis B virus (HBV) co-infection. We present feasibility and efficacy of DTG/3TC in newly diagnosed individuals in a test-and-treat setting. DESIGN: The single-arm STAT study evaluated DTG/3TC in a US test-and-treat setting. METHODS: Eligible adults initiated DTG/3TC 14 days or less after HIV-1 diagnosis without availability of baseline laboratory results. If baseline testing indicated DTG or 3TC resistance, HBV co-infection, or creatinine clearance less than 30 ml/min per 1.73 m2, participants remained on study with treatment modification. Efficacy endpoints included proportions of participants with HIV-1 RNA less than 50 copies/ml at Week 24, regardless of antiretroviral regimen, among all participants (intention-to-treat exposed) and those with available HIV-1 RNA data (observed). RESULTS: Of 131 participants enrolled, 8% were female and 50% were non-white. Through Week 24, treatment was modified in eight participants [five with HBV co-infection, one with baseline M184V, one for adverse event (rash), one participant decision]. At Week 24, 78% (102/131) of all participants and 92% (102/111) of those with available data achieved HIV-1 RNA less than 50 copies/ml. Incidence of drug-related adverse events was low (7%); no drug-related serious adverse events occurred. CONCLUSION: These data demonstrate the feasibility, efficacy, and safety of using DTG/3TC as a first-line regimen in a test-and-treat setting, with therapy adjustments for baseline resistance or HBV co-infection occurring safely via routine clinical care as needed [ClinicalTrials.gov, NCT03945981; see Supplemental Digital Content 1, video abstract (Video abstract summarizing the STAT study design and results), http://links.lww.com/QAD/C189].


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Adulto , Fármacos Anti-HIV/efeitos adversos , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Lamivudina/efeitos adversos , Masculino , Oxazinas/uso terapêutico , Piperazinas/uso terapêutico , Piridonas
11.
Toxicol Appl Pharmacol ; 244(2): 196-207, 2010 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-20045428

RESUMO

A novel physiologically based pharmacokinetic (PBPK) model structure, which includes submodels for the common metabolites (glyoxylate (GXA) and oxalate (OXA)) that may be involved in the toxicity or carcinogenicity of dibromoacetic acid (DBA), has been developed. Particular attention is paid to the representation of hepatic metabolism, which is the primary elimination mechanism. DBA-induced suicide inhibition is modeled by irreversible covalent binding of the intermediate metabolite alpha-halocarboxymethylglutathione (alphaH1) to the glutathione-S-transferase zeta (GSTzeta) enzyme. We also present data illustrating the presence of a secondary non-GSTzeta metabolic pathway for DBA, but not dichloroacetic acid (DCA), that produces GXA. The model is calibrated with plasma and urine concentration data from DBA exposures in female F344 rats through intravenous (IV), oral gavage, and drinking water routes. Sensitivity analysis is performed to confirm identifiability of estimated parameters. Finally, model validation is performed with data sets not used during calibration. Given the structural similarity of dihaloacetates (DHAs), we hypothesize that the PBPK model presented here has the capacity to describe the kinetics of any member or mixture of members of this class in any species with the alteration of chemical-and species-specific parameters.


Assuntos
Ácido Dicloroacético/farmacocinética , Modelos Biológicos , Animais , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Knockout , Ratos , Ratos Endogâmicos F344 , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/fisiologia
12.
Nitric Oxide ; 22(1): 30-6, 2010 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19914388

RESUMO

We report the therapeutic potential of S-nitroso-N-acetylpenicillamine-derivatized generation-4 polyamidoamine dendrimers (G4-SNAP) for reducing ischemia/reperfusion (I/R) injury in an isolated, perfused rat heart. The use of this dendrimer scaffold to deliver the nitrosothiol therapeutic did not inhibit NO donor activity as the required dose of G4-SNAP to minimize I/R injury (31nM corresponding to 2microM SNAP) was consistent with the optimum concentration of small molecule SNAP alone. An exploration of G4-SNAP NO release kinetics in the presence of physiologically relevant concentrations of glutathione (GSH) indicated enhanced NO release (t[NO]=1.28microM NO/mg) at 500microM GSH. Reperfusion experiments conducted with 500microM GSH further lowered the optimal therapeutic G4-SNAP dose to 230pM (i.e., 15nM SNAP). The unique combination of G4-SNAP dendrimer and glutathione trigger represents a novel strategy with possible clinical relevance toward salvaging ischemic tissue.


Assuntos
Dendrímeros/farmacologia , Glutationa/farmacologia , Óxido Nítrico/metabolismo , Poliaminas/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Células Cultivadas , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo
13.
Sci Total Environ ; 740: 140093, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32540744

RESUMO

Little is known about the environmental conditions that drive the spatiotemporal patterns of SARS-CoV-2. Preliminary research suggests an association with meteorological parameters. However, the relationship with temperature and humidity is not yet apparent for COVID-19 cases in US cities first impacted. The objective of this study is to evaluate the association between COVID-19 cases and meteorological parameters in select US cities. A case-crossover design with a distributed lag nonlinear model was used to evaluate the contribution of ambient temperature and specific humidity on COVID-19 cases in select US cities. The case-crossover examines each COVID case as its own control at different time periods (before and after transmission occurred). We modeled the effect of temperature and humidity on COVID-19 transmission using a lag period of 7 days. A subset of 8 cities were evaluated for the relationship with meteorological parameters and 5 cities were evaluated in detail. Short-term exposure to humidity was positively associated with COVID-19 transmission in 4 cities. The associations were small with 3 out of 4 cities exhibiting higher COVID19 transmission with specific humidity that ranged from 6 to 9 g/kg. Our results suggest that weather should be considered in infectious disease modeling efforts. Future work is needed over a longer time period and across different locations to clearly establish the weather-COVID19 relationship.


Assuntos
Infecções por Coronavirus , Umidade , Temperatura , Betacoronavirus , COVID-19 , Cidades , Infecções por Coronavirus/mortalidade , Humanos , Pandemias , Pneumonia Viral/mortalidade , SARS-CoV-2
14.
Transl Behav Med ; 10(3): 637-647, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32766868

RESUMO

Lifestyle-related diseases have common risk factors: physical inactivity, poor diet, inadequate sleep, high stress, substance use, and social isolation. Evidence is mounting for the benefits of incorporating effective methods that promote healthy lifestyle habits into routine health care treatments. Research has established that healthy habits foster psychological and physiological health and that emotional well-being is central to achieving total well-being. The Happiness Science and Positive Health Committee of the American College of Lifestyle Medicine aims to raise awareness about strategies for prioritizing emotional well-being. The Committee advocates for collaborative translational research to adapt the positive psychology and behavioral medicine evidence base into methodologies that address emotional well-being in nonmental health care settings. Another aim is to promote health system changes that integrate evidence-based positive-psychology interventions into health maintenance and treatment plans. Also, the Committee seeks to ameliorate health provider burnout through the application of positive psychology methods for providers' personal health. The American College of Lifestyle Medicine and Dell Medical School held an inaugural Summit on Happiness Science in Health Care in May 2018. The Summit participants recommended research, policy, and practice innovations to promote total well-being via lifestyle changes that bolster emotional well-being. These recommendations urge stakeholder collaboration to facilitate translational research for health care settings and to standardize terms, measures, and clinical approaches for implementing positive psychology interventions. Sample aims of joint collaboration include developing evidence-based, practical, low-cost behavioral and emotional assessment and monitoring tools; grants to encourage dissemination of pilot initiatives; medical record dashboards with emotional well-being and related aspects of mental health as vital signs; clinical best practices for health care teams; and automated behavioral programs to extend clinician time. However, a few simple steps for prioritizing emotional well-being can be implemented by stakeholders in the near-term.


Assuntos
Promoção da Saúde , Psicologia Positiva , Atenção à Saúde , Instalações de Saúde , Humanos , Saúde Mental , Estados Unidos
15.
J Acquir Immune Defic Syndr ; 85(3): 325-330, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32675772

RESUMO

BACKGROUND: The SWORD trials showed that in participants who achieved virologic suppression taking 3-drug or 4-drug regimens, switching to the 2-drug regimen dolutegravir plus rilpivirine was noninferior in maintaining HIV-1 RNA <50 copies/mL at the week 48 primary endpoint. We present pooled week 148 analysis results from both studies. SETTING: SWORD-1: 65 centers, 13 countries; SWORD-2: 60 centers, 11 countries. METHODS: SWORD-1 and SWORD-2 are identical, open-label, phase III studies. Participants with screening HIV-1 RNA <50 copies/mL for ≥6 months; no prior virologic failure; and no documented resistance-associated major protease inhibitor, integrase inhibitor, nucleoside reverse transcriptase inhibitor (NRTI), or non-NRTI mutations or integrase resistance-associated substitution R263K were randomly assigned 1:1 to switch to once-daily dolutegravir 50 mg plus rilpivirine 25 mg on day 1 (early-switch group) or to continue their current antiretroviral regimen and, if virologically suppressed at week 48, switch to dolutegravir plus rilpivirine at week 52 (late-switch group) until week 148. RESULTS: Using snapshot algorithm at week 148, 432 of 513 (84%) early-switch participants (148 weeks of exposure) and 428 of 477 (90%) late-switch participants (96 weeks of exposure) maintained HIV-1 RNA <50 copies/mL. Eleven participants (1%) on dolutegravir plus rilpivirine met the confirmed virologic withdrawal criterion through week 148 (early-switch group, n = 8; late-switch group, n = 3) with no integrase resistance identified. Non-NRTI resistance-associated mutations were identified in 6 participants (<1%). Drug-related adverse events (grades 2-4) were observed in 31 (6%) early-switch and 16 (3%) late-switch participants. Significant improvements in bone biomarkers were observed. Significant improvements were observed in renal biomarkers in participants taking tenofovir disoproxil fumarate pre-switch. CONCLUSION: Switching to the 2-drug regimen dolutegravir plus rilpivirine maintained virologic suppression for a high proportion of participants through 3 years, with low rates of virologic failure and a well-tolerated safety profile.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1 , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Rilpivirina/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Esquema de Medicação , Combinação de Medicamentos , Feminino , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Rilpivirina/administração & dosagem , Rilpivirina/efeitos adversos , Carga Viral
16.
Lancet HIV ; 6(9): e576-e587, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31307948

RESUMO

BACKGROUND: Primary analyses of the SWORD-1 and SWORD-2 trials at 48 weeks showed that switching to a two-drug regimen of dolutegravir plus rilpivirine was non-inferior to continuing a standard three-drug or four-drug antiretroviral regimen for maintenance of virological suppression in people with HIV-1. Here, we present efficacy and safety data from the 100-week analysis of the trials. METHODS: SWORD-1 and SWORD-2 are identically designed, randomised, open-label phase 3 studies at 65 centres in 13 countries and 60 centres in 11 countries, respectively. Adults aged 18 years or older who were on a standard three-drug or four-drug antiretroviral therapy (ART) and had had fewer than 50 HIV-1 RNA copies per mL of plasma for at least 6 months were randomly assigned (1:1) to 50 mg dolutegravir plus 25 mg rilpivirine orally once daily (early-switch group) or to continue their standard regimen for 52 weeks before switching to the dolutegravir plus rilpivirine combination (ie, the late-switch group). In this analysis of week 100 data, the efficacy endpoint of interest was the proportion of participants with fewer than 50 copies of HIV-1 RNA per mL of plasma (per the US Food and Drug Administration snapshot algorithm). This outcome was assessed in all randomly assigned participants who received at least one dose of the study drug. Data were analysed after the last participant completed week 100 (Sept 15, 2017) and verified through the data cutoff (Nov 21, 2017). SWORD-1 and SWORD-2 are registered with ClinicalTrials.gov, numbers NCT02429791 and NCT02422797, respectively. FINDINGS: 513 participants were randomly assigned to dolutegravir plus rilpivirine (ie, the early-switch group) and 511 to continue their standard ART regimen, 477 of whom then switched to dolutegravir plus rilpivirine at week 52 (ie, the late-switch group). At week 100, 456 (89% [95% CI 86-92]) of 513 participants in the early-switch group and 444 (93% [91-95]) of 477 in the late-switch group had fewer than 50 HIV-1 RNA copies per mL. Drug-related adverse events occurred in 103 (20%) participants in the early-switch group and 58 (12%) in the late-switch group. The most common drug-related adverse events were headache (11 participants in the early-switch group [2%] vs eight [2%] in the late-switch group) and nausea (eight [2%] vs five [1%]). INTERPRETATION: The combination of dolutegravir plus rilpivirine sustained virological suppression of HIV-1, was associated with a low frequency of virological failure, and had a favourable safety profile, which support its use as a nucleoside reverse transcriptase inhibitor-sparing and protease inhibitor-sparing alternative to three-drug regimens that reduces overall exposure to ART. FUNDING: ViiV Healthcare and Janssen Pharmaceutica.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Rilpivirina/uso terapêutico , Adolescente , Adulto , Quimioterapia Combinada , Feminino , Infecções por HIV/sangue , Infecções por HIV/virologia , Inibidores de Integrase de HIV/efeitos adversos , HIV-1/metabolismo , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Piridonas , Inibidores da Transcriptase Reversa/efeitos adversos , Rilpivirina/efeitos adversos , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Adulto Jovem
17.
J Clin Endocrinol Metab ; 93(12): 4810-7, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18812476

RESUMO

CONTEXT: Native glucagon-like peptide-1 increases insulin secretion, decreases glucagon secretion, and reduces appetite but is rapidly inactivated by dipeptidyl peptidase-4. Albiglutide is a novel dipeptidyl peptidase-4-resistant glucagon-like peptide-1 dimer fused to human albumin designed to have sustained efficacy in vivo. OBJECTIVES: The objectives were to investigate pharmacodynamics, pharmacokinetics, safety, and tolerability of albiglutide in type 2 diabetes subjects. METHODS: In a single-blind dose-escalation study, 54 subjects were randomized to receive placebo or 9-, 16-, or 32-mg albiglutide on d 1 and 8. In a complementary study, 46 subjects were randomized to a single dose (16 or 64 mg) of albiglutide to the arm, leg, or abdomen. RESULTS: Significant dose-dependent reductions in 24-h mean weighted glucose [area under the curve((0-24 h))] were observed, with placebo-adjusted least squares means difference values in the 32-mg cohort of -34.8 and -56.4 mg/dl [95% confidence interval (-54.1, -15.5) and (-82.2, -30.5)] for d 2 and 9, respectively. Placebo-adjusted fasting plasma glucose decreased by -26.7 and -50.7 mg/dl [95% confidence interval (-46.3, -7.06) and (-75.4, -26.0)] on d 2 and 9, respectively. Postprandial glucose was also reduced. No hypoglycemic episodes were detected in the albiglutide cohorts. The frequency and severity of the most common adverse events, headache and nausea, were comparable with placebo controls. Albiglutide half-life ranged between 6 and 7 d. The pharmacokinetics or pharmacodynamic of albiglutide was unaffected by injection site. CONCLUSIONS: Albiglutide improved fasting plasma glucose and postprandial glucose with a favorable safety profile in subjects with type 2 diabetes. Albiglutide's long half-life may allow for once-weekly or less frequent dosing.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Peptídeo 1 Semelhante ao Glucagon/fisiologia , Hipoglicemiantes/uso terapêutico , Adolescente , Adulto , Idoso , Área Sob a Curva , Glicemia/metabolismo , Relação Dose-Resposta a Droga , Feminino , Peptídeo 1 Semelhante ao Glucagon/efeitos adversos , Peptídeo 1 Semelhante ao Glucagon/farmacocinética , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Hemoglobinas Glicadas/metabolismo , Meia-Vida , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacocinética , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Mimetismo Molecular , Adulto Jovem
18.
J Fam Pract ; 71(Suppl 1 Lifestyle): eS93-eS99, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35389854
19.
Postgrad Med ; 128(4): 391-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27043162

RESUMO

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) vary in their structure, duration of action, efficacy, and safety. In order to optimize glycemic control, it is important to target both fasting (FPG) and postprandial plasma (PPG) glucose. Although phase 3 trials document the effect of GLP-1 RAs on glycated hemoglobin, few data are available to assess their effect on PPG. Albiglutide is a once-weekly GLP-1 RA with a half-life of ≈ 5 days. The goal of this review is to summarize the effects of albiglutide on PPG in four phase 2 trials and to describe the PPG-lowering effects of the GLP-1 RAs. At clinically relevant doses (30-64 mg), albiglutide consistently lowered PPG after each meal in addition to its effect on lowering FPG. Multiple weekly subcutaneous injections of albiglutide led to improvements in a variety of glycemic measures, including maximal reductions in PPG from baseline, postmeal glucose excursions, and FPG. Albiglutide, a longer-acting GLP-1 RAs, provides reductions in FPG, PPG following meals, and glucose over 24 hours.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Hipoglicemiantes/administração & dosagem , Período Pós-Prandial , Ensaios Clínicos Fase II como Assunto , Diabetes Mellitus Tipo 2/sangue , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Acad Emerg Med ; 11(6): 642-7, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15175202

RESUMO

OBJECTIVES: To evaluate the hypothesis that computed tomography (CT) angiography often yields a result interpreted as an alternative diagnosis to pulmonary embolism (PE) in emergency department (ED) patients. METHODS: This was a multicenter, retrospective, and secondary analysis of consecutive patients in three academic emergency departments. ED patients with symptoms suspicious for PE were included. CT angiography was ordered at the discretion of the treating physician; patients were identified by query of the electronic medical record. Board-certified radiologists gave CT readings, which were reviewed by two independent emergency physicians who categorized the non-PE findings into one of four acuity categories: A = requiring specific and immediate intervention, B = requiring specific action on follow-up, C = requiring no action, and D = indeterminate findings. RESULTS: The prevalence of PE among the 1,025 patients studied was 10% (95% CI = 8% to 12%). In the 921 patients without PE, the mean prevalences (ranges between sites) of concordant categorized non-PE findings were: A = 7% (range 3%-11%), B = 10% (7%-13%), C = 17% (10%-20%), D = 4% (0%-8%), and no ancillary finding = 41% (29% to 45%). The most common category A findings included infiltrate or consolidation suggesting pneumonia (81%), aortic aneurysm or dissection (7%), and mass suggesting undiagnosed malignancy (7%). The overall unweighted agreement was 80% (kappa = 0.72) and weighted agreement was 93% (kappa(w) = 0.84). CONCLUSIONS: In ED patients with suspected PE, the CT angiogram frequently provides evidence suggesting an important alternative diagnosis to PE. Pulmonary infiltrate suggesting pneumonia was the most common non-PE finding.


Assuntos
Serviços Médicos de Emergência/métodos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Embolia Pulmonar/diagnóstico por imagem , Radiografia Torácica/métodos , Radiografia Torácica/estatística & dados numéricos , Angiografia/métodos , Angiografia/estatística & dados numéricos , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/epidemiologia , Arizona/epidemiologia , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Humanos , Illinois/epidemiologia , Pneumopatias/diagnóstico por imagem , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Avaliação de Processos e Resultados em Cuidados de Saúde , Pneumonia/diagnóstico por imagem , Pneumonia/epidemiologia , Prevalência , Embolia Pulmonar/epidemiologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/estatística & dados numéricos
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