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1.
Pediatr Res ; 93(4): 990-995, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35854087

RESUMO

BACKGROUND: Examine the real-world clinical impact of adopting less invasive surfactant administration (LISA) as the primary surfactant administration method in extremely preterm infants. METHODS: Single-center pre-post cohort study conducted over a 4-year period comparing outcomes of spontaneously breathing inborn infants 24+0-28+6 weeks gestational age (GA) receiving surfactant via endotracheal tube (pre-cohort, n = 154) or LISA via thin catheter (post-cohort, n = 70). Primary outcome was need for invasive mechanical ventilation (IMV, ≥2 h) ≤72 h of age. Secondary outcomes were a composite of mortality, bronchopulmonary dysplasia, intraventricular hemorrhage ≥grade 3 or necrotizing enterocolitis, and its individual components. Groups were compared using propensity score methods, including covariates: GA, birth weight, sex, small for GA, SNAP II ≥20, premature rupture of membranes, maternal hypertension/diabetes, and C-section. RESULTS: GA and birth weight were 27.1 (26, 28.1) weeks and 914 (230) g, and 27.1 (26.1, 28.1) weeks and 920 (236) g for pre- and post-cohorts, respectively. Pre-cohort had higher C-section rates, (67% vs. 51%, p = 0.03). After adjustment for covariates, LISA was associated with reduced IMV exposure [AOR (95% CI) 0.07 (0.04, 0.11)], lower odds of the composite clinical outcome [0.49 (0.33, 0.73)], and most of its individual components. CONCLUSION: Real-world experience favors LISA as the primary method in extremely preterm infants with established spontaneous respiration. IMPACT: Less invasive surfactant administration (LISA) is associated with a reduction in respiratory morbidity, but real-world data of routine use among extremely preterm infants are limited. LISA is associated with reduced frequency of exposure to and duration of IMV in both ≤72 h after birth and during hospital stay. LISA is associated with a reduction in mortality, and most other major morbidities including bronchopulmonary dysplasia, and interventricular hemorrhage. Data from a large North American center providing real-world clinical outcomes following LISA as the primary method of surfactant administration.


Assuntos
Displasia Broncopulmonar , Surfactantes Pulmonares , Síndrome do Desconforto Respiratório do Recém-Nascido , Lactente , Feminino , Recém-Nascido , Humanos , Lactente Extremamente Prematuro , Tensoativos/uso terapêutico , Estudos de Coortes , Peso ao Nascer , Laringoscopia , Surfactantes Pulmonares/uso terapêutico , Respiração Artificial/métodos , Lipoproteínas , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico
2.
J Environ Manage ; 323: 116225, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36115245

RESUMO

Biogenic taste and odour (T&O) have become a global concern for water utilities, due to the increasing frequency of algal blooms and other microbial events arising from the combined effects of climate change and eutrophication. Microbially-produced T&O compounds impact source waters, drinking water treatment plants, and drinking water distribution systems. It is important to manage across the entire biogenic T&O pathway to identify key risk factors and devise strategies that will safeguard the quality of drinking water in a changing world, since the presence of T&O impacts consumer confidence in drinking water safety. This study provides a critical review of current knowledge on T&O-causing microbes and compounds for proactive management, including the identification of abiotic risk factors in source waters, a discussion on the effectiveness of existing T&O barriers in drinking water treatment plants, an analysis of risk factors for biofilm growth in water distribution systems, and an assessment of the impacts of T&O on consumers. The fate of biogenic T&O in drinking water systems is tracked from microbial production pathways, through the release of intracellular T&O by cell lysis, to the treatment of microbial cells and dissolved T&O. Based on current knowledge, five impactful research and management directions across the T&O pathway are recommended.


Assuntos
Água Potável , Purificação da Água , Água Potável/análise , Eutrofização , Odorantes/análise , Paladar , Abastecimento de Água
3.
J Sex Med ; 19(8): 1281-1289, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35780013

RESUMO

BACKGROUND: Genito-pelvic pain (GPP) affects a sizable minority of women and results of existing treatments can be variable. A method of general pain treatment that has not yet been extended to penetration-related GPP is Explicit Motor Imagery (EMI), which uses pain-related images to help individuals with pain alter their responses to pain, resulting in reduced pain, less pain-related anxiety, and improved function. AIM: As a first step toward determining if EMI is a feasible method for treating penetration-related GPP, this study examined whether images that potentially signal genital pain are sufficient to induce an anxiety or anticipated pain response in women. METHODS: Participants were 113 women (62 with genital pain, 51 pain-free) recruited to complete an online study. Participants viewed randomized images of women engaging in various activities that potentially cause pain for people with penetration-related GPP (sitting, walking, running, lifting, inserting a tampon, implied penetrative sex, actual penetrative sex, implied gynecological exam, actual gynecological exam). Participants then rated each image on how much anxiety they experienced viewing the picture (viewing anxiety), and how much anxiety (anticipated anxiety) and pain (anticipated pain) they expected to experience doing the activity in the picture. OUTCOMES: Outcomes were the self-reported viewing anxiety, anticipated anxiety, and anticipated pain of women with and without self-reported penetration-related GPP in response to the pain-related images. RESULTS: Women who experienced self-reported penetration-related GPP reported significantly higher levels of viewing anxiety, anticipated anxiety, and anticipated pain in almost all categories of images, compared to women who were free of pain. The key exception was that women with and without self-reported penetration-related GPP reported similar levels of viewing anxiety when looking at images of implied and actual penetrative sex. CLINICAL TRANSLATION: These results support that pelvic and genital imagery serve as a sufficient stimulus to generate anxiety and anticipated pain in our study sample. EMI, which targets desensitization of heightened anxiety warrants further research as a potential novel treatment option. STRENGTHS & LIMITATIONS: This study was the first to assess responses to a wide array of pain-eliciting images in women with and without self-reported penetration-related GPP. A key limitation was that the pain sample was self-reported and not clinically diagnosed. CONCLUSION: Images of pain-related stimuli were sufficient to induce anxiety and anticipated pain in women with self-reported penetration-related GPP. This first step suggests that EMI may be a useful treatment option for women with penetration-related GPP. Kelly KJM, Fisher BL, Rosen NO, et al. Anxiety and Anticipated Pain Levels of Women With Self-Reported Penetration-Related Genito-Pelvic Pain are Elevated in Response to Pain-related Images. J Sex Med 2022;19:1281-1289.


Assuntos
Ansiedade , Dor Pélvica , Transtornos de Ansiedade , Feminino , Humanos , Autoimagem , Autorrelato
6.
Telemed J E Health ; 27(12): 1409-1415, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33661708

RESUMO

Introduction: The unprecedented COVID-19 pandemic has thrust telehealth into the center stage of health care, leading to a dramatic increase in utilization of telehealth services. The impact of telehealth on patient satisfaction during the current pandemic is yet to be fully understood. Objective: This study aimed to identify patient perspectives and behaviors toward virtual primary care appointments at a telehealth-naïve institution during the COVID-19 pandemic and establish the rate of missed appointments to help guide future implementation of telehealth services. Methods: Patients at a primary and specialty care clinic, seen between March and May 2020, completed a survey analyzing nine commonly used satisfaction metrics. The rate of missed appointments was recorded and compared with analogous cohorts of in-person office visits. Results: The no-show rate of telehealth visits during the COVID-19 pandemic was 7.5% (14/186), lower than both the no-show rate of 36.1% for in-office visits (56/155) (p < 0.0001) and a pre-pandemic in-office no-show rate of 29.8% (129/433) (p < 0.0001). Surveyed patients who experienced telehealth visits (n = 65) had similar satisfaction compared with those surveyed who attended in-office visits (n = 36) in seven of nine metrics. No statistically significant differences were identified in the satisfaction metrics with telehealth visits performed on video (n = 26) versus the phone-only format (n = 38). Patients aged 65 years or over were less likely to have a video component to their virtual visit (1/12, 8.3%) than those under age 65 (25/44, 56.8%) (p = 0.0031). Discussion/Conclusions: Telehealth offers significant benefits for both patients and providers, strongly supporting its widespread utilization both during and following the COVID-19 pandemic.


Assuntos
COVID-19 , Telemedicina , Idoso , Instituições de Assistência Ambulatorial , Humanos , Pandemias , Satisfação do Paciente , SARS-CoV-2
7.
J Nutr Educ Behav ; 52(7): 742-746, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31932229

RESUMO

There is a documented substantial gap between the level of nutrition education for medical trainees and the need to provide nutrition counseling. Culinary medicine offers a solution, but there are multiple barriers and no guides to implementation. This article identifies core components and strategies to overcome barriers on the basis of experiences of multiple institutions. The outline forms a foundation to be built upon by future collaborators to empower more widespread implementation of culinary medicine education and improve medical nutrition education and ultimately, patient outcomes.


Assuntos
Culinária , Educação Médica , Educação em Saúde , Ciências da Nutrição/educação , Currículo , Humanos
9.
Clin Pharmacol Drug Dev ; 8(3): 281-289, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30676701

RESUMO

We evaluated the pharmacokinetics, pharmacodynamics, and safety of evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), in an open-label, parallel-design study in participants with normal renal function (n = 6), severe renal impairment (RI; n = 6), or end-stage renal disease (ESRD) receiving hemodialysis (n = 6) who received a single 140-mg dose of evolocumab. The effects of evolocumab treatment on low-density lipoprotein cholesterol (LDL-C) lowering and unbound PCSK9 concentrations were similar in the normal renal function group and the renally impaired groups. Geometric mean Cmax and AUClast values in the severe RI and ESRD hemodialysis groups compared with the normal renal function group were lower but within 37% of the normal renal function group (Jonckheere-Terpstra trend test; Cmax , P = .23; AUClast , P = .22) and within 26% after adjusting for body weight (mean body weight was approximately 9% higher in the renally impaired groups compared with the normal renal function group). No correlations were observed between exposure and baseline creatinine clearance. No adverse event was determined by the investigators to be related to evolocumab, and there were no trends indicative of clinically important effects on laboratory variables or vital signs. Overall, there were no meaningful differences in evolocumab exposure, as assessed by Cmax and AUClast , in patients with severe RI and ESRD hemodialysis compared with patients with normal renal function, and LDL-C-lowering effects were similar across groups. These results support the use of evolocumab without dose adjustment in patients who have severe RI or ESRD.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/farmacologia , LDL-Colesterol/sangue , Falência Renal Crônica/tratamento farmacológico , Rim/efeitos dos fármacos , Anticorpos Monoclonais Humanizados/farmacocinética , Anticolesterolemiantes/farmacocinética , Área Sob a Curva , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Injeções Subcutâneas , Rim/fisiopatologia , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Inibidores de PCSK9 , Pró-Proteína Convertase 9/sangue , Ligação Proteica , Diálise Renal
10.
J Ultrasound Med ; 38(4): 967-973, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30280401

RESUMO

OBJECTIVES: Chest radiography has been the preferred imaging study to assess pulmonary congestion. However, chest radiography interpretation is influenced by the level of expertise and high interobserver variability. Lung ultrasound (US) may produce more objective findings through evaluation of vertical comet tail artifacts known as B-lines, which are created by a decrease in the ratio of alveolar air to fluid pulmonary content. Few studies have directly compared chest radiography to bedside US against a reference standard for the diagnosis of pulmonary edema. This study compared the sensitivity and specificity of bedside US and chest radiography in diagnosing pulmonary edema. METHODS: This prospective observational cohort study involved adult patients presenting to the emergency department of an urban tertiary hospital with dyspnea. The primary outcome was the presence or absence of pulmonary edema, as indicated by B-lines on a bedside lung US examination or radiologist-interpreted chest radiography. Patients underwent a US examination within about 1 hour of chest radiography. The final diagnosis from the discharge summary served as the reference standard. RESULTS: Ninety-nine patients were enrolled; 32.3% had congestive heart failure, and 40.4% had chronic obstructive pulmonary disease. Bedside US showed significantly higher sensitivity (96%) compared to chest radiography (65%; P < .001). Of 18 patients with negative radiographic findings and a discharge diagnosis of pulmonary edema, 16 (89%) had positive US findings (P < .001). CONCLUSIONS: Bedside US has the potential to identify pulmonary edema more accurately than chest radiography. As current practice within the United States uses chest radiography, reflecting American College of Cardiology Foundation/American Heart Association guidelines for management of heart failure, the results of this study warrant further evaluation.


Assuntos
Sistemas Automatizados de Assistência Junto ao Leito , Edema Pulmonar/diagnóstico por imagem , Radiografia Torácica/métodos , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Sensibilidade e Especificidade
11.
Adv Ther ; 35(10): 1713-1728, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30191465

RESUMO

INTRODUCTION: Osteoporosis is characterized by low bone mineral density (BMD) and an increased risk of fracture. In randomized controlled trials, denosumab has been shown to significantly reduce the fracture risk in women with osteoporosis. However, little is known about the real-world management of women who are prescribed denosumab. METHODS: This multicenter, prospective, observational real-world study in the Czech Republic and Slovakia evaluated the baseline characteristics and clinical management of women with postmenopausal osteoporosis prescribed denosumab for 24 months. RESULTS: A total of 600 women were included (300 in each country). In the Czech Republic and Slovakia, respectively, mean age at enrollment was 69.0 and 64.3 years, 67.7% and 30.0% of patients had a previous osteoporotic fracture, and 85.0% and 48.7% had previously received osteoporosis medication. In both countries, 'low BMD T score' and 'a history of osteoporotic fracture' were the main reasons for prescribing denosumab. Most patients received all four post-baseline denosumab injections (Czech Republic, 82.0%; Slovakia, 81.0%), and more than 98% of patients in both countries received all injections at the prescribing center. At 24 months, most patients experienced an increase in BMD T score for the lumbar spine, total hip, or femoral neck (Czech Republic, 69.7-91.7%; Slovakia, 67.1-92.9%). Adverse drug reactions were consistent with the known safety profile of denosumab. CONCLUSION: Baseline characteristics of patients receiving denosumab in the Czech Republic and Slovakia reflect the reimbursement criteria for this agent in each country. The findings of our study in patients who are at high risk for fracture are consistent with the growing body of evidence demonstrating the effectiveness of denosumab in real-world clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01652690. FUNDING: Amgen Inc.


Assuntos
Denosumab , Osteoporose Pós-Menopausa , Fraturas por Osteoporose , Idoso , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , República Tcheca/epidemiologia , Denosumab/administração & dosagem , Denosumab/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/epidemiologia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Avaliação de Resultados em Cuidados de Saúde , Serviços Preventivos de Saúde/métodos , Serviços Preventivos de Saúde/estatística & dados numéricos , Estudos Prospectivos , Medição de Risco , Eslováquia/epidemiologia
12.
J Sex Marital Ther ; 44(1): 73-86, 2018 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-28441101

RESUMO

Pornography availability has increased in recent years, and while there is plenty of speculation about its effects, empirical investigation about how porn influences our lives has yielded mixed results. Additionally, few studies have addressed the effects of specific pornography characteristics. Past research has shown that male-centric pornography can be related to negative outcomes, while female-centric pornography is related to more positive outcomes, particularly in women. The present survey study examined the relationship between pornography characteristics (male- and female-centric) and the self-reported attitudes and sexual experiences of men and women. Participants in the full sample were 195 men and 310 women who completed an online questionnaire. Although effect sizes were small, women who reported viewing pornography with more female-centric features also reported more positive effects of pornography on sex life and perceptions of the other gender. While men were more likely than women to report negative effects relating to pornography use on these same measures, there were very few reported negative effects of pornography overall. These findings demonstrate a small association between the use of female-centric pornography and more positive outcomes, particularly for women.


Assuntos
Atitude Frente a Saúde , Comportamento Sexual/psicologia , Parceiros Sexuais/psicologia , Percepção Social , Literatura Erótica , Feminino , Heterossexualidade/psicologia , Humanos , Masculino , Fatores Sexuais , Comportamento Sexual/estatística & dados numéricos , Inquéritos e Questionários , Adulto Jovem
13.
Clin Pharmacol Ther ; 103(5): 815-825, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28736918

RESUMO

Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) signaling are being explored as prophylactic treatments for migraine. Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of the CGRP receptor. We report the data from two phase I studies assessing the safety, pharmacokinetics (PK), and pharmacodynamics of single and multiple administrations of erenumab in healthy subjects and patients with migraine. The results indicate that the PK profile of erenumab is nonlinear from 1 mg to 70 mg and the linear portion of the clearance from 70 mg to 210 mg is consistent with other human immunoglobulin G2 antibodies. Single doses of erenumab resulted in >75% inhibition of capsaicin-induced dermal blood flow, with no apparent dose-dependency for erenumab ≥21 mg. Erenumab was generally well tolerated, with an acceptable safety profile, supporting further clinical development of erenumab for migraine prevention.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Adolescente , Adulto , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adulto Jovem
14.
Arch Sex Behav ; 46(8): 2289-2299, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28905269

RESUMO

In non-human animal research, studies comparing socially monogamous and promiscuous species of voles (Microtus) have identified some key neural differences related to monogamy and non-monogamy. Specifically, densities of the vasopressin V1a receptor and dopamine D2 receptors in subcortical reward-related and limbic areas of the brain have been linked to monogamous behavior in prairie voles (Microtus ochrogaster). Similar brain areas have been shown to be correlated with feelings of romantic love in monogamously pair-bonded humans. Humans vary in the degree to which they engage in (non-)monogamous behaviors. The present study examined the differences in neural activation in response to sexual and romantic stimuli in monogamous (n = 10) and non-monogamous (n = 10) men. Results indicated that monogamous men showed more reward-related neural activity when viewing romantic pictures compared to non-monogamous men. Areas with increased activation for monogamous men were all in the right hemisphere and included the thalamus, accumbens, striatum, pallidum, insula, and orbitofrontal cortex. There were no significant differences between groups in activation to sexual stimuli. These results demonstrate that the neural processing of romantic images is different for monogamous and non-monogamous men. There is some overlap in the neural areas showing increased activation in monogamous men in the present study and the neural areas that show differences in the vole models of monogamy and affiliation. Future research will be needed to clarify whether similar factors are contributing to the neural differences seen in monogamous and non-monogamous humans and voles.


Assuntos
Comportamento Sexual/fisiologia , Parceiros Sexuais , Animais , Arvicolinae , Feminino , Humanos , Masculino
15.
Pharm Res ; 34(9): 1784-1795, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28593473

RESUMO

PURPOSE: Capsaicin-induced dermal blood flow (CIDBF) is a validated biomarker used to evaluate the target engagement of potential calcitonin gene-related peptide-blocking therapeutics for migraine. To characterize the pharmacokinetics (PK) and quantify the inhibitory effects of erenumab (AMG 334) on CIDBF, CIDBF data were pooled from a single- and a multiple-dose study in healthy and migraine subjects. METHODS: Repeated capsaicin challenges and DBF measurements were performed and serum erenumab concentrations determined. A population analysis was conducted using a nonlinear mixed-effects modeling approach. Effects of body weight, gender, and age on model parameters were evaluated. RESULTS: Two-compartment target-mediated drug disposition (TMDD) model assuming binding of erenumab in the central compartment best described the nonlinear PK of erenumab. Subcutaneous absorption half-life was 1.6 days and bioavailability was 74%. Erenumab produced a maximum inhibition of 89% (95% confidence interval: 87-91%). Erenumab concentrations required for 50% and 99% of maximum inhibition were 255 ng/mL and 1134 ng/mL, respectively. Increased body weight was associated with increased erenumab clearance but had no effect on the inhibitory effect on CIDBF. CONCLUSIONS: Our results show that erenumab pharmacokinetics was best characterized by a TMDD model and resulted in potent inhibition of CIDBF.


Assuntos
Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/farmacologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores , Capsaicina/farmacologia , Transtornos de Enxaqueca/tratamento farmacológico , Fármacos do Sistema Sensorial/farmacologia , Pele/irrigação sanguínea , Adulto , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Masculino , Transtornos de Enxaqueca/fisiopatologia , Modelos Biológicos , Adulto Jovem
16.
J Clin Pharmacol ; 57(4): 513-523, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27667740

RESUMO

Evolocumab binds PCSK9, increasing low-density lipoprotein cholesterol (LDL-C) receptors and lowering LDL-C. Target-mediated evolocumab elimination is attributable to PCSK9 binding. As circulating PCSK9 and LDL-C levels are primarily regulated by the liver, we compared evolocumab pharmacokinetics, pharmacodynamics, and safety in individuals with and without hepatic impairment. An open-label, parallel-group study evaluated the pharmacokinetics of evolocumab in hepatic-impaired (Child-Pugh Class A or B) or healthy adults. Participants were classified as having no, mild, or moderate hepatic impairment (n = 8/group) and received a single 140-mg evolocumab dose. Assessments of unbound evolocumab and PCSK9 were made predose and postdose. Adverse events were monitored throughout the study. No significant association was observed between baseline PCSK9 and increasing level of hepatic impairment. No difference in extent and time course of PCSK9 or LDL-C reduction was observed despite an apparent decrease in mean unbound evolocumab exposure with increasing hepatic impairment (Jonckheere-Terpstra trend test; maximum serum concentration P = .18; area under the curve P = .09). Maximum reductions were observed in moderately impaired subjects vs healthy individuals: mean maximum serum concentration -34%; mean area under the concentration-time curve (AUC) -47%. On average, unbound PCSK9 serum concentrations fell by >80% at 4 hours after a single evolocumab dose. Mean (95% confidence interval) maximum LDL-C reductions in the healthy, mild, and moderate groups were -57% (-64% to -48%), -70% (-75% to -63%), and -53% (-61% to -43%), respectively. No safety risks were identified. These results support evolocumab use without dose adjustment in patients with active liver disease and mild or moderate hepatic impairment.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/sangue , Imunoglobulina G/administração & dosagem , Imunoglobulina G/sangue , Hepatopatias/sangue , Pró-Proteína Convertase 9/sangue , Adulto , Anticorpos Monoclonais Humanizados , LDL-Colesterol/sangue , Feminino , Humanos , Injeções Subcutâneas , Hepatopatias/tratamento farmacológico , Masculino , Pessoa de Meia-Idade
17.
J Lipid Res ; 57(12): 2217-2224, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27707817

RESUMO

The effects of cholesterol-lowering drugs, including those that reduce cholesterol synthesis (statins) and those that reduce cholesterol absorption (ezetimibe), on cholesterol absorption and synthesis are well understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a novel class of cholesterol-lowering drugs that robustly reduce LDL-cholesterol (LDL-C), but little is known about their effects on cholesterol absorption and synthesis. We evaluated how treatment with evolocumab, a fully human monoclonal IgG2 antibody to PCSK9, affects markers of cholesterol synthesis and absorption by measuring these markers in patients from an evolocumab clinical trial. At 2 weeks, changes in ß-sitosterol/total cholesterol (TC) from baseline were 4% for placebo, 10% for evolocumab 140 mg (nonsignificant vs. placebo), and 26% for evolocumab 420 mg (P < 0.001 vs. placebo). Changes in campesterol/TC at week 2, relative to baseline between placebo and evolocumab, were all nonsignificant. Evolocumab had a modest effect on markers of cholesterol synthesis. At 2 weeks, changes in desmosterol/TC were 1% for placebo, 7% for evolocumab 140 mg (nonsignificant vs. placebo), and 15% for evolocumab 420 mg (P < 0.01 vs. placebo). Changes from baseline in lathosterol/TC at week 2 between placebo and evolocumab were nonsignificant. These results suggest that evolocumab has a modest effect on cholesterol synthesis and absorption despite significant LDL-C lowering.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Hipercolesterolemia/tratamento farmacológico , Absorção Intestinal/efeitos dos fármacos , Adulto , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Anticolesterolemiantes/farmacologia , LDL-Colesterol/biossíntese , Feminino , Humanos , Hipercolesterolemia/sangue , Masculino , Pessoa de Meia-Idade , Sitosteroides/sangue , Resultado do Tratamento
18.
Sci Total Environ ; 560-561: 101-9, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27096490

RESUMO

The impact of changes in influent load on the removal of endocrine disrupting chemicals (EDCs) by sewage treatment has not been fully characterised. This study assessed the efficacy of an advanced tertiary sewage treatment plant (STP) to remove EDCs during normal and peak flow events of sewage influent using trace chemical analysis of selected EDCs and four estrogenic in vitro bioassays. During the summer holiday season, influent volume increased by 68%, nutrient concentrations by at least 26% and hydraulic retention time was reduced by 40% compared with base flow conditions. Despite these pressures on the treatment system the concentrations and mass loading of estrone, 17ß-estradiol, estriol, Bisphenol A, 4-t-octylphenol and technical nonylphenol were not significantly higher (p>0.05) during the peak flow conditions compared with base flow conditions. Chemical analysis and in vitro bioassays showed that the efficacy of the STP in removing EDCs was not affected by the different loadings between baseline and peak flow regimes. This study demonstrates that large flow variations within the design capacity of advanced multi-stage STPs should not reduce the removal efficacy of EDCs.


Assuntos
Disruptores Endócrinos/análise , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Compostos Benzidrílicos/análise , Estradiol/análise , Estriol/análise , Fenóis/análise
19.
Br J Radiol ; 89(1058): 20150735, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26559441

RESUMO

OBJECTIVE: To compare the accuracy of standard supplementary views and GE digital breast tomosynthesis (DBT) for assessment of soft-tissue mammographic abnormalities. METHODS: Women recalled for further assessment of soft-tissue abnormalities were recruited and received standard supplementary views (typically spot compression views) and two-view GE DBT. The added value of DBT in the assessment process was determined by analysing data collected prospectively by radiologists working up the cases. Following anonymization of cases, there was also a retrospective multireader review. The readers first read bilateral standard two-view digital mammography (DM) together with the supplementary mammographic views and gave a combined score for suspicion of malignancy on a five-point scale. The same readers then read bilateral standard two-view DM together with two-view DBT. Pathology data were obtained. Differences were assessed using receiver operating characteristic analysis. RESULTS: The study population was 342 lesions in 322 patients. The final diagnosis was malignant in 113 cases (33%) and benign/normal in 229 cases (67%). In the prospective analysis, the performance of two-view DM plus DBT was at least equivalent to the performance of two-view DM and standard mammographic supplementary views-the area under the curve (AUC) was 0.946 and 0.922, respectively, which did not reach statistical significance. Similar results were obtained for the retrospective review-AUC was 0.900 (DBT) and 0.873 (supplementary views), which did not reach statistical significance. CONCLUSION: The accuracy of GE DBT in the assessment of screen detected soft-tissue abnormalities is equivalent to the use of standard supplementary mammographic views. ADVANCES IN KNOWLEDGE: The vast majority of evidence relating to the use of DBT has been gathered from research using Hologic equipment. This study provides evidence for the use of the commercially available GE DBT system demonstrating that it is at least equivalent to supplementary mammographic views in the assessment of soft-tissue screen-detected abnormalities.


Assuntos
Doenças Mamárias/diagnóstico por imagem , Mamografia , Intensificação de Imagem Radiográfica/métodos , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Imageamento Tridimensional , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade
20.
Psychooncology ; 25(7): 848-56, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26332203

RESUMO

OBJECTIVE: To assess the relationship between of androgen deprivation therapy (ADT) and the mood of prostate cancer (PCa) patients and partners of PCa patients. METHODS: PCa patients (n = 295) and partners of patients (n = 84) completed an online survey assessing the patients' current mood and mood prior to treatment, relationship adjustment, and sexual function. We compared men on ADT to men who received non-hormonal treatments for their PCa. RESULTS: Patients currently treated with ADT (n = 82) reported worsened mood as measured by the Profile of Mood States compared to those not on ADT (n = 213). The negative impact of ADT on mood, however, was reduced in older patients. Partners of patients on ADT (n = 42) reported similar declines in the patient's mood that patients reported, but to a greater degree than patient-reported levels. CONCLUSIONS: Our data support ADT's impact on PCa patients' mood and verify that partners concurrently see the effects. The psychological changes related to ADT can impact relationships and affect the quality of life of both PCa patients and partners. Patients and their partners are likely to benefit from being well informed about the psychological effects of androgen deprivation on men beginning ADT. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.


Assuntos
Afeto , Antagonistas de Androgênios/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/psicologia , Disfunções Sexuais Fisiológicas/psicologia , Cônjuges/psicologia , Idoso , Antineoplásicos Hormonais/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida/psicologia
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