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1.
Rev Esp Salud Publica ; 952021 Oct 08.
Artigo em Espanhol | MEDLINE | ID: mdl-34620826

RESUMO

OBJECTIVE: Frailty is an increasing problem among the elderly people and it is more frequent in women. Physical activity improves either the function and quality of life. Given the diferences reported by the literature about the quality of life perception and the physical activity practice between men and women, the aim of this study is to analyze the association between health related quality of life (HRQoL) and physical activity in a pre-frail population and to study its relationship with gender. METHODS: Descriptive study in pre-frail individuals over 70 years old assigned to twelve primary care health centers carried out between 2018 Jun and 2020 March in Madrid. The studied variables were registered by clinical interview: Physical activity (Yale), HRQoL (EQ-5D-3L), sociodemographic and clinical variables (comorbidity, depression and pain). Descriptive analysis and multiple linear regression for the whole population and stratified by gender, using the quality of life as dependent variable. RESULTS: The study involved 206 pre-frail individuals (152 women) wih an average age of 78 years. Women had less comorbidity (32.3% versus 55.6%) but more pain (60.5% versus 44.4%) than men. The median of physical activity was 40 points (55.9% of that score was attributable to relaxed walk). HRQoL was 0.74 in utility score and 68 in the EQ-VAS. No differences were found by gender. To walk more than 5 hours a week was found associated with better quality of life by EQ-5D utility score (0.08, IC95%: 0.03 to 0.14), and by EQ-VAS score (5.38, IC95%: 0.25 to 10.51). CONCLUSIONS: Physical activity was associated to better quality of life in a pre-frail population of individuals older than 70 years old.


Assuntos
Exercício Físico , Qualidade de Vida , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Atenção Primária à Saúde , Espanha , Inquéritos e Questionários
2.
Artigo em Inglês | MEDLINE | ID: mdl-34682462

RESUMO

Participation of pregnant women in clinical trials entails challenges mainly related to concerns about the risks for fetuses. We undertook a qualitative study from June to October 2020 to assess the acceptability of participating in COVID-19 clinical trials among pregnant women in Spain. Phenomenology and grounded theory were used as methodological approaches. Semi-structured interviews were conducted with 24 pregnant women and six healthcare providers. Women were unsure if pregnancy was a risk factor to acquire the infection or to develop severe disease and expressed the limited information they had received, which led to uncertainties and emotional suffering. They had concerns regarding participation in clinical trials on COVID-19, regardless of the drug under study. Healthcare providers alluded to the importance of involving pregnant women's relatives at the recruitment visit of the clinical trial. These findings may be useful to facilitate pregnant women's participation in clinical trials.

3.
Prostate ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34516663

RESUMO

BACKGROUND: Among men with metastatic prostate cancer, about 10% have germline alterations in DNA damage response genes. Most studies have examined BRCA2 alone or an aggregate of BRCA1/2 and ATM. Emerging data suggest that ATM mutations may have distinct biology and warrant individual evaluation. The objective of this study is to determine whether response to prostate cancer systemic therapies differs between men with germline mutations in ATM (gATM) and BRCA2 (gBRCA2). METHODS: This is an international multicenter retrospective matched cohort study of men with prostate cancer harboring gATM or gBRCA2. PSA50 response (≥50% decline in prostate-specific antigen) was compared using Fisher's exact test. RESULTS AND LIMITATIONS: The study included 45 gATM and 45 gBRCA2 patients, matched on stage and year of germline testing. Patients with gATM and gBRCA2 had similar age, Gleason grade, and PSA at diagnosis. We did not observe differences in PSA50 responses to abiraterone, enzalutamide, or docetaxel in metastatic castration resistant prostate cancer between the two groups; however, 0/7 with gATM and 12/14 with gBRCA2 achieved PSA50 response to PARPi (p < .001). Median (95% confidence interval) overall survival from diagnosis to death was 10.9 years (9.5-not reached) versus 9.9 years (7.1-not reached, p = .07) for the gATM and gBRCA2 cohorts, respectively. Limitations include the retrospective design and lack of mutation zygosity data. CONCLUSIONS: Conventional therapies can be effective in gATM carriers and should be considered before PARPi, which shows limited efficacy in this group. Men with gATM mutations warrant prioritization for novel treatment strategies.

4.
Eur J Obstet Gynecol Reprod Biol ; 265: 162-168, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34508989

RESUMO

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) transmitted primarily by Aedes mosquitoes. ZIKV can be transmitted to humans by non-vector borne mechanisms such as sexual intercourse, maternal-foetal transmission or blood transfusion. In 2015, ZIKV emerged in the Americas, and spread to 87 countries and territories with autochthonous transmission, distributed across four of the six WHO regions. Most ZIKV infections in pregnancy are asymptomatic, but mother to child transmission of the virus can occur in 20 to 30% of cases and cause severe foetal and child defects. Children exposed to ZIKV while in utero might develop a pattern of structural anomalies and functional disabilities secondary to central nervous system damage, known as congenital Zika syndrome, and whose most common clinical feature is microcephaly. Normocephalic children born to mothers with ZIKV infection in pregnancy, and with no observable Zika-associated birth defects, may also present with later neurodevelopmental delay or post-natal microcephaly. Screening and detection of ZIKV infection in pregnancy is essential, because most women with ZIKV infection are asymptomatic and clinical manifestations are non-specific. However, the diagnosis of ZIKV infection poses multiple challenges due to limited resources and scarce laboratory capabilities in most affected areas, the narrow window of time that the virus persists in the bloodstream, the large proportion of asymptomatic infections, and the cross-reactivity with other flaviviruses such as Dengue virus (DENV). Molecular methods (RT-PCR) are the most reliable tool to confirm ZIKV infection, as serodiagnosis requires confirmation with neutralization tests in case of inconclusive or positive serology results. Prenatal ultrasound assessment is essential for monitoring foetal development and early detection of possible severe anomalies. A mid- and long-term follow-up of children exposed to ZIKV while in utero is necessary to promptly detect clinical manifestations of possible neurological impairment. Tweetable abstract: Zika virus infection during pregnancy is a cause of pregnancy loss and disability in children. Protection against mosquito bites, access to sexual and reproductive health services, prompt screening and detection of ZIKV infection in pregnancy, and prenatal ultrasound monitoring are key control strategies whilst a vaccine is not available.


Assuntos
Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Animais , Criança , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Gestantes , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia
5.
Cancers (Basel) ; 13(18)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34572748

RESUMO

The treatment landscape of advanced prostate cancer has completely changed during the last decades. Chemotherapy (docetaxel, cabazitaxel), androgen-receptor signaling inhibitors (ARSi) (abiraterone acetate, enzalutamide), and radium-223 have revolutionized the management of metastatic castration-resistant prostate cancer (mCRPC). Lutetium-177-PSMA-617 is also going to become another treatment option for these patients. In addition, docetaxel, abiraterone acetate, apalutamide, enzalutamide, and radiotherapy to primary tumor have demonstrated the ability to significantly prolong the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Finally, apalutamide, enzalutamide, and darolutamide have recently provided impactful data in patients with nonmetastatic castration-resistant disease (nmCRPC). However, which is the best treatment sequence for patients with advanced prostate cancer? This comprehensive review aims at discussing the available literature data to identify the optimal sequencing approaches in patients with prostate cancer at different disease stages. Our work also highlights the potential impact of predictive biomarkers in treatment sequencing and exploring the role of specific agents (i.e., olaparib, rucaparib, talazoparib, niraparib, and ipatasertib) in biomarker-selected populations of patients with prostate cancer (i.e., those harboring alterations in DNA damage and response genes or PTEN).

6.
PLoS One ; 16(9): e0257546, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34587191

RESUMO

OBJECTIVE: To analyze trends in urinary tract infection hospitalization (cystitis, pyelonephritis, prostatitis and non-specified UTI) among patients over 65 years in Spain from 2000-2015. METHODS: We conducted a retrospective observational study using the Spanish Hospitalization Minimum Data Set (CMBD), with codifications by the International Classification of Diseases (ICD-9). We collected data on sex, age, type of discharge, main diagnosis, comorbid diagnosis, length of stay, and global cost. All the hospitalizations were grouped by age into three categories: 65-74 years old, 75-84 years old, and 85 years old and above. In the descriptive statistical analysis, crude rates were defined as hospitalizations per 1,000 inhabitants aged ≥65. To identify trends over time, we performed a Joinpoint regression. RESULTS: From 2000-2015, we found 387,010 hospitalizations coded as UTIs (54,427 pyelonephritis, 15,869 prostatitis, 2643 cystitis and 314,071 non-specified UTI). The crude rate of hospitalization for UTIs between 2000 and 2015 ranged from 2.09 in 2000 to 4.33 in 2015 Rates of hospitalization were higher in men than in women, except with pyelonephritis. By age group, higher rates were observed in patients aged 85 years or older, barring prostatitis-related hospitalizations. Joinpoint analyses showed an average annual percentage increase (AAPC) in incidence rates of 4.9% (95% CI 3.2;6.1) in UTI hospitalizations. We observed two joinpoints, in 2010 and 2013, that found trends of 5.5% between 2000 and 2010 (95% CI 4.7;6.4), 1.5% between 2010 and 2013 (95% CI -6.0;9.6) and 6.8% between 2013 and 2015 (95% CI -0.3;14.4). CONCLUSIONS: The urinary infection-related hospitalization rate in Spain doubled during the period 2000-2015. The highest hospitalization rates occurred in men, in the ≥85 years old age group, and in non-specified UTIs. There were increases in all types of urinary tract infection, with non-specified UTIs having the greatest growth. Understanding these changing trends can be useful for health planning.

7.
J Community Psychol ; 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34352131

RESUMO

Critical consciousness (CC) may promote well-being, particularly during the COVID-19 pandemic. In a national survey of 707 college students conducted in April 2020, we first validated the Short Critical Consciousness Scale (ShoCCS) among youth groups not often specifically examined in CC measurement (i.e., Asian, immigrant-origin, LGBQ+, and women youth). Next, we examined associations between ShoCCS subscales and validated measures of both anxiety (Generalized Anxiety Disorder-7) and hopefulness (The Individual-Differences Measure in Hopefulness). The ShoCCS achieved measurement invariance across racial/ethnic groups and immigrant-origin status, and partial invariance among LGBQ+ and women-identifying youth. We found critical reflection and action associated with anxiety for the full sample, but no evidence of moderation by sociodemographic factors. ShoCCS subscales were differentially associated with hopefulness for Asian youth and LGBQ+ youth. This study contributes to the evolution of CC measurement and extends the field by identifying well-being associations during the onset of the COVID-19 pandemic.

8.
Lancet Oncol ; 22(9): 1250-1264, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34388386

RESUMO

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors have antitumour activity against metastatic castration-resistant prostate cancers with DNA damage response (DDR) alterations in genes involved directly or indirectly in homologous recombination repair (HRR). In this study, we assessed the PARP inhibitor talazoparib in metastatic castration-resistant prostate cancers with DDR-HRR alterations. METHODS: In this open-label, phase 2 trial (TALAPRO-1), participants were recruited from 43 hospitals, cancer centres, and medical centres in Australia, Austria, Belgium, Brazil, France, Germany, Hungary, Italy, the Netherlands, Poland, Spain, South Korea, the UK, and the USA. Patients were eligible if they were men aged 18 years or older with progressive, metastatic, castration-resistant prostate cancers of adenocarcinoma histology, measurable soft-tissue disease (per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]), an Eastern Cooperative Oncology Group performance status of 0-2, DDR-HRR gene alterations reported to sensitise to PARP inhibitors (ie, ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C), had received one or two taxane-based chemotherapy regimens for metastatic disease, and progressed on enzalutamide or abiraterone, or both, for metastatic castration-resistant prostate cancers. Eligible patients were given oral talazoparib (1 mg per day; or 0·75 mg per day in patients with moderate renal impairment) until disease progression, unacceptable toxicity, investigator decision, withdrawal of consent, or death. The primary endpoint was confirmed objective response rate, defined as best overall soft-tissue response of complete or partial response per RECIST 1.1, by blinded independent central review. The primary endpoint was assessed in patients who received study drug, had measurable soft-tissue disease, and had a gene alteration in one of the predefined DDR-HRR genes. Safety was assessed in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, NCT03148795, and is ongoing. FINDINGS: Between Oct 18, 2017, and March 20, 2020, 128 patients were enrolled, of whom 127 received at least one dose of talazoparib (safety population) and 104 had measurable soft-tissue disease (antitumour activity population). Data cutoff for this analysis was Sept 4, 2020. After a median follow-up of 16·4 months (IQR 11·1-22·1), the objective response rate was 29·8% (31 of 104 patients; 95% CI 21·2-39·6). The most common grade 3-4 treatment-emergent adverse events were anaemia (39 [31%] of 127 patients), thrombocytopenia (11 [9%]), and neutropenia (ten [8%]). Serious treatment-emergent adverse events were reported in 43 (34%) patients. There were no treatment-related deaths. INTERPRETATION: Talazoparib showed durable antitumour activity in men with advanced metastatic castration-resistant prostate cancers with DDR-HRR gene alterations who had been heavily pretreated. The favourable benefit-risk profile supports the study of talazoparib in larger, randomised clinical trials, including in patients with non-BRCA alterations. FUNDING: Pfizer/Medivation.


Assuntos
Antineoplásicos/uso terapêutico , Reparo do DNA/genética , Ftalazinas/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Idoso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/patologia , Critérios de Avaliação de Resposta em Tumores Sólidos , Análise de Sobrevida
9.
Eur Urol ; 80(5): 641-649, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34373138

RESUMO

BACKGROUND: Most available prognostic nomograms in metastatic castration-resistant prostate cancer (mCRPC) are derived from datasets not representative of the current treatment landscape. A prognostic nomogram for first-line mCRPC treatment was developed from patients treated in the PREVAIL study. OBJECTIVE: To validate the Armstrong model in the COU-AA-302 trial. DESIGN, SETTING, AND PARTICIPANTS: A post hoc analysis of mCRPC patients treated in the COU-AA-302 trial was carried out (NCT00887198). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The Armstrong prognostic model was applied to patients treated in COU-AA-302. A continuous risk score was derived from coefficients from the original model. Time-dependent area under the curve (tAUC) was used to evaluate the overall predictive ability of the model. Patients were categorized according to the number of risk factors present into those at a low (three or fewer risk factors), intermediate (four to six risk factors), and high (seven to ten risk factors) risk. The association with survival was assessed with Cox regression models. Interaction tests were used to assess the impact of treatment arm in each of the prognostic groups. RESULTS AND LIMITATIONS: A total of 1088 patients were analyzed. The risk score was associated with overall survival (OS; tAUC 0.733). Most patients were at a low (49%) or intermediate (41%) risk. Risk category was significantly associated with OS (hazard ratio [HR]: 2.3; 95% confidence interval [CI]: 1.9-2.4; p < 0.001), radiographic progression-free survival (rPFS; HR: 1.7; 95% CI: 1.5-1.8; p < 0.001), and prostate-specific antigen progression-free survival (HR: 1.7; 95% CI: 1.5-1.9; p < 0.001). A significant interaction between risk group and OS (p = 0.007) and rPFS (p = 0.009) was observed. Survival was superior in low-risk patients (HR: 0.73; 95% CI: 0.59-0.89; p = 0.009), but similar in intermediate-risk (HR: 0.97; 95% CI: 0.79-1.21; p = 0.9) and high-risk (HR: 1.35; 95% CI: 0.80-2.28; p = 0.5) patients. Two-year OS rates in abiraterone versus placebo were 82% versus 74% in low-risk, 55% versus 52% in intermediate-risk, and 28% versus 31% in high-risk patients. CONCLUSIONS: We validate the prognostic value of the Armstrong risk model in patients treated with first-line androgen receptor signaling inhibitors. Abiraterone provided a greater benefit in low-risk patients with less aggressive disease. Further research is needed to establish the role of Armstrong risk groups for treatment selection in mCRPC patients. PATIENT SUMMARY: In this report, we validated the Armstrong nomogram in the COU-AA-302 trial population. We found a similar prognostic performance to that of the original model. Good-risk patients received the greatest benefit from abiraterone.

10.
Int J Mol Sci ; 22(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34445375

RESUMO

Fast and sustained antidepressant effects of ketamine identified the mammalian target of rapamycin (mTOR) signaling pathway as the main modulator of its antidepressive effects. Thus, mTOR signaling has become integral for the preclinical evaluation of novel compounds to treat depression. However, causality between mTOR and depression has yet to be determined. To address this, we knocked down mTOR expression in mice using an acute intracerebral infusion of small interfering RNAs (siRNA) in the infralimbic (IL) or prelimbic (PrL) cortices of the medial prefrontal cortex (mPFC), and evaluated depressive- and anxious-like behaviors. mTOR knockdown in IL, but not PrL, cortex produced a robust depressive-like phenotype in mice, as assessed in the forced swimming test (FST) and the tail suspension test (TST). This phenotype was associated with significant reductions of mTOR mRNA and protein levels 48 h post-infusion. In parallel, decreased brain-derived neurotrophic factor (BDNF) expression was found bilaterally in both IL and PrL cortices along with a dysregulation of serotonin (5-HT) and glutamate (Glu) release in the dorsal raphe nucleus (DRN). Overall, our results demonstrate causality between mTOR expression in the IL cortex and depressive-like behaviors, but not in anxiety.


Assuntos
Depressão/psicologia , Córtex Pré-Frontal/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/genética , Depressão/metabolismo , Modelos Animais de Doenças , Núcleo Dorsal da Rafe/metabolismo , Técnicas de Silenciamento de Genes , Ácido Glutâmico/metabolismo , Elevação dos Membros Posteriores , Masculino , Camundongos , Serotonina/metabolismo , Natação
11.
Front Nutr ; 8: 656730, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34235167

RESUMO

Sarcopenia is characterised by the presence of diminished skeletal muscle mass and strength. It is relatively common in older adults as ageing is associated with anabolic resistance (a blunted muscle protein synthesis response to dietary protein consumption and resistance exercise). Therefore, interventions to counteract anabolic resistance may benefit sarcopenia prevention and are of utmost importance in the present ageing population. There is growing speculation that the gut microbiota may contribute to sarcopenia, as ageing is also associated with [1) dysbiosis, whereby the gut microbiota becomes less diverse, lacking in healthy butyrate-producing microorganisms and higher in pathogenic bacteria, and [2) loss of epithelial tight junction integrity in the lining of the gut, leading to increased gut permeability and higher metabolic endotoxemia. Animal data suggest that both elements may impact muscle physiology, but human data corroborating the causality of the association between gut microbiota and muscle mass and strength are lacking. Mechanisms wherein the gut microbiota may alter anabolic resistance include an attenuation of gut-derived low-grade inflammation and/or the increased digestibility of protein-containing foods and consequent higher aminoacidemia, both in favour of muscle protein synthesis. This review focuses on the putative links between the gut microbiota and skeletal muscle in the context of sarcopenia. We also address the issue of plant protein digestibility because plant proteins are increasingly important from an environmental sustainability perspective, yet they are less efficient at stimulating muscle protein synthesis than animal proteins.

12.
Front Mol Neurosci ; 14: 582497, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093123

RESUMO

Research on microglia has established the differentiation between the so-called M1 and M2 phenotypes. However, new frameworks have been proposed attempting to discern between meaningful microglia profiles. We have set up an in vitro microglial activation model by adding an injured spinal cord (SCI) lysate to microglial cultures, obtained from postnatal rats, in order to mimic the environment of the spinal cord after injury. We found that under the presence of the SCI lysate microglial cells changed their phenotype, developing less ramified but longer processes, and proliferated. The SCI lysate also led to upregulation of pro-inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, downregulation of the anti-inflammatory cytokines IL-10 and IL-4, and a biphasic profile of iNOS. In addition, a latex beads phagocytosis assay revealed the SCI lysate stimulated the phagocytic capacity of microglia. Flow cytometry analysis indicated that microglial cells showed a pro-inflammatory profile in the presence of SCI lysate. Finally, characterization of the microglial activation in the spinal cord on day 7 after contusion injury, we showed that these cells have a pro-inflammatory phenotype. Overall, these results indicate that the use of SCI lysates could be a useful tool to skew microglia towards a closer phenotype to that observed after the spinal cord contusion injury than the use of LPS or IFNγ.

13.
Cancers (Basel) ; 13(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066080

RESUMO

Circulating tumor cell (CTC) enumeration and changes following treatment have been demonstrated to be superior to PSA response in determining mCRPC outcome in patients receiving AR signaling inhibitors but not taxanes. We carried out a pooled analysis of two prospective studies in mCRPC patients treated with docetaxel. CTCs were measured at baseline and 3-6 weeks post treatment initiation. Cox regression models were constructed to compare 6-month radiographical progression-free survival (rPFS), CTCs and PSA changes predicting outcome. Among the subjects, 80 and 52 patients had evaluable baseline and post-treatment CTC counts, respectively. A significant association of higher baseline CTC count with worse overall survival (OS), PFS and time to PSA progression (TTPP) was observed. While CTC response at 3-6 weeks (CTC conversion (from ≥5 to <5 CTCs), CTC30 (≥30% decline in CTC) or CTC0 (decline to 0 CTC)) and 6-month rPFS were significantly associated with OS (all p < 0.005), the association was not significant for PSA30 or PSA50 response. CTC and PSA response were discordant in over 50% of cases, with outcome driven by CTC response in these patients. The c-index values for OS were superior for early CTC changes compared to PSA response endpoints, and similar to 6-month rPFS. Early CTC declines were good predictors of improved outcomes in mCRPC patients treated with docetaxel in this small study, offering a superior and/or earlier estimation of docetaxel benefit in comparison to PSA or rPFS that merits further confirmation in larger studies.

14.
Eur J Cancer ; 152: 49-59, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34077818

RESUMO

BACKGROUND: Plasma AR status has been identified as a potential biomarker of response in metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel or AR-targeted therapies. However, the relevance of plasma AR in the overall management of CRPC patients receiving different docetaxel doses is unknown. PATIENTS AND METHODS: This was a multi-institution study of associations between baseline plasma AR copy number status, assessed by droplet digital PCR, and outcome in 325 mCRPC patients receiving docetaxel at standard or adapted regimen at the discretion of the treating physician. Upon analysis, patients were assigned randomly to either a training (n = 217) or validation (n = 108) cohort. RESULTS: In the training cohort, AR-gained patients treated with adapted docetaxel regimen had a significantly worse median progression-free survival (PFS) (3.8 vs 6.3 months, hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.34-4.95, p < 0.0001), median overall survival (10.8 vs 20.6 months, HR 1.98, 95% CI 1.09-3.62, p = 0.0064) and PSA response (PSA > -50%: odds ratio 4.88 95%CI 1.55-14.32, p = 0.013) as compared to plasma AR normal patients. These findings were all confirmed in the validation cohort. However, in patients treated with standard docetaxel regimen, these differences were not seen. The interaction between AR CN status and dose reduction of docetaxel was considered as independent factor for PFS in both the training and validation cohort (HR 2.84, 95% CI 1.41-5.73, p = 0.003, and HR 4.79, 95% CI 1.79-12.82, p = 0.002). CONCLUSION: Despite the retrospective non-randomised design of this study, our hypothesis-generating findings could suggest plasma AR as a potential biomarker for optimal docetaxel timing and dose in mCRPC patients. Prospective trials are warranted.

15.
ACS Chem Neurosci ; 12(11): 2036-2044, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-33974408

RESUMO

Clinical and preclinical studies report the implication of 5-hydroxytryptamine 4 receptors (5-HT4Rs) in depression and anxiety. Here, we tested whether the absence of 5-HT4Rs influences the response to the antidepressant fluoxetine in mice subjected to chronic corticosterone administration, an animal model of depression and anxiety. Therefore, the effects of chronic administration of fluoxetine in corticosterone-treated wild-type (WT) and 5-HT4R knockout (KO) mice were evaluated in the open-field and novelty suppressed feeding tests. As 5-HT1A receptor (5-HT1AR) and brain-derived neurotrophic factor (BDNF) are critically involved in depression and anxiety, we further evaluated 5-HT1A receptor functionality by [35S]GTPγS autoradiography and BDNF mRNA expression by in situ hybridization techniques. We found that 5-HT4R KO and WT mice displayed anxiety- and depressive-like behavior following chronic administration of corticosterone, as evidenced in the open-field and novelty suppressed feeding tests. In the open-field, a decreased central activity was observed in naïve and corticosterone-treated mice of both genotypes following chronic fluoxetine administration. In the novelty suppressed feeding test, a predictive paradigm of antidepressant activity, chronic treatment with fluoxetine reverted the latency to eat in both genotypes. The antidepressant also potentiated the corticosterone-induced desensitization of the 5-HT1AR in the dorsal raphe nucleus. Further, chronic fluoxetine increased BDNF mRNA expression in the dentate gyrus of the hippocampus in corticosterone-treated mice of both genotypes. Therefore, our findings indicate that the behavioral effects of fluoxetine in the corticosterone model of depression and anxiety appear not to be dependent on 5-HT4Rs.


Assuntos
Corticosterona , Fluoxetina , Animais , Ansiedade , Depressão/tratamento farmacológico , Fluoxetina/farmacologia , Hipocampo , Camundongos , Serotonina
16.
Cost Eff Resour Alloc ; 19(1): 27, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952285

RESUMO

BACKGROUND: The preferences of citizens are a basic element to incorporate into the decision-making process when planning health policies. Contingent valuation (CV) is a common method for calculating the value for citizens that new technologies, interventions, and the provision of services or policies have. However, choosing the correct CV tool may not be a neutral decision. This work aims to assess the substitution of a healthcare service by comparing valuation differences between the willingness to pay (WTP) for the maintenance of the service versus the willingness to accept compensation (WTA) for its substitution, both of which are related to subject characteristics, with a particular focus on trust in institutions and risk aversion. METHODS: A CV study was designed to study Dutch population preferences when physician assistants replace anaesthesiologists. Differences between the distributions of WTA and WTP were compared through full decomposition methods, and conditional quantile regression was performed. RESULTS: Nearly two-thirds of surveyed citizens expressed null values for WTA and WTP. The other third systematically reported a value of WTA higher than that of WTP, which increased further with lower income and the possible presence of a strategic bias. In contrast, being more than 65 years old, having trust in government, and preferring anaesthesiologists decreased the WTA-WTP difference. Risk aversion had no clear association with the WTA-WTP gap. CONCLUSIONS: Known differences between the perceived value of health services from the perspective of gains and losses could be related to people's characteristics. Trust in government but not aversion to risk was related to the WTA-WTP differences. Identifying a profile of citizens who are averse to losing health services should be considered when designing and implementing health services or interventions or making disinvestment decisions.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33956466

RESUMO

OBJECTIVES: In recent years, increased anti-immigrant hostility has trickled into school settings creating toxic climates for immigrant-origin (I-O) students (Rogers, School and society in the age of trump, 2019, UCLA's Institute for Democracy, Education, and Access). Through youth participatory action research (yPAR), this study qualitatively examined how a class of Emerging Bilingual (EB) students aimed to promote more inclusive learning environments by designing, implementing, and evaluating a school-wide program. Here, we consider how the students experienced growth in their civic development as well as how they contended with resistances encountered during the project. METHODS: The current study took place at a majority I-O, northeastern high school and was led by an EB class (n = 20) and its teacher. Participants were as follows: on average 16.5 years; 60% female; and 65% Latinx, 30% Black, and 5% mixed-race (Black-Latino). Multiple data sources documenting the students' experiences were collected (including weekly student reflections and ethnographic field notes) and then thematically analyzed using open coding. RESULTS: Participating students demonstrated civic development as evidenced through: growing confidence that the program could generate positive change; enhanced sense of connection toward their classmates; and increased commitment to future civic engagement. Nonetheless, some participants demonstrated initial trepidation in both disclosing their migration stories as well as the potential efficacy of engaging in the project. Furthermore, others were disappointed by the disinterest displayed by some of their peers and teachers. CONCLUSIONS: Collaborative research can support I-O youths' civic development, though, the resistances encountered and engendered illuminate possible challenges to ensure its benefits. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

18.
Rev Esp Salud Publica ; 952021 Apr 06.
Artigo em Espanhol | MEDLINE | ID: mdl-33820907

RESUMO

OBJECTIVE: Toxic oil syndrome is a multisystemic disease that arose in 1981 due to the ingestion of contaminated rapeseed oil. Previous studies have found a higher prevalence of cardiovascular risk factors in these patients. The aim of this study was to analyze the differences in the prevalence of chronic diseases among a population affected by Toxic oil syndrome compared with a reference population in the Community of Madrid. METHODS: Cross-sectional observational study of patients with a registry diagnosed with Toxic oil syndrome in the primary care medical record and a reference sample without Toxic oil syndrome matched by age group and sex. Sociodemographic variables, cardiovascular risk factors, cardiovascular and cerebrovascular disease, anxiety, depression, asthma, chronic obstructive pulmonary disease, and low back pain, and multimorbidity (≥2 chronic diseases) were assesed. Descriptive and multivariate analysis was performed to study the association between morbidity and Toxic oil syndrome. RESULTS: 3,527 patients (1,394 Toxic oil syndrome) were included with a mean age of 66 (SD14) years, 71% women. Patients with a diagnosis of SAT were more likely to present multimorbidity (OR 1.36; 95%CI: 1.10-1.45), diabetes (OR 1.55; 95%CI: 1.29-1.86), complicated hypertension (OR 1.77; IC95%: 1.31-2.39), heart attack (OR 2.23; 95%CI: 1.47-3.38), depression (OR 1.39; 95%CI: 1.17-1.66) and asthma (OR 1.56; 95%CI: 1.23-1.97). The prevalence of anxiety was lower in TOS (OR 0.35; 95% CI: 0.18-0.69) as well as low back pain (OR 0.77; 95%CI: 0.65-0.91). CONCLUSIONS: Patients with toxic oil syndrome have a higher frequency of chronic diseases and mutimorbidity compared to the general population of the same sex and age.


Assuntos
Doença Crônica/epidemiologia , Multimorbidade , Óleo de Brassica napus/toxicidade , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espanha/epidemiologia , Síndrome
19.
Am J Clin Nutr ; 113(6): 1411-1427, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33871558

RESUMO

BACKGROUND: Leucine-enriched protein (LEU-PRO) and long-chain (LC) n-3 (ω-3) PUFAs have each been proposed to improve muscle mass and function in older adults, whereas their combination may be more effective than either alone. OBJECTIVE: The impact of LEU-PRO supplementation alone and combined with LC n-3 PUFAs on appendicular lean mass, strength, physical performance and myofibrillar protein synthesis (MyoPS) was investigated in older adults at risk of sarcopenia. METHODS: This 24-wk, 3-arm parallel, randomized, double-blind, placebo-controlled trial was conducted in 107 men and women aged ≥65 y with low muscle mass and/or strength. Twice daily, participants consumed a supplement containing either LEU-PRO (3 g leucine, 10 g protein; n = 38), LEU-PRO plus LC n-3 PUFAs (0.8 g EPA, 1.1 g DHA; LEU-PRO+n-3; n = 38), or an isoenergetic control (CON; n = 31). Appendicular lean mass, handgrip strength, leg strength, physical performance, and circulating metabolic and renal function markers were measured pre-, mid-, and postintervention. Integrated rates of MyoPS were assessed in a subcohort (n = 28). RESULTS: Neither LEU-PRO nor LEU-PRO+n-3 supplementation affected appendicular lean mass, handgrip strength, knee extension strength, physical performance or MyoPS. However, isometric knee flexion peak torque (treatment effect: -7.1 Nm; 95% CI: -12.5, -1.8 Nm; P < 0.01) was lower postsupplementation in LEU-PRO+n-3 compared with CON. Serum triacylglycerol and total adiponectin concentrations were lower, and HOMA-IR was higher, in LEU-PRO+n-3 compared with CON postsupplementation (all P < 0.05). Estimated glomerular filtration rate was higher and cystatin c was lower in LEU-PRO and LEU-PRO+n-3 postsupplementation compared with CON (all P < 0.05). CONCLUSIONS: Contrary to our hypothesis, we did not observe a beneficial effect of LEU-PRO supplementation alone or combined with LC n-3 PUFA supplementation on appendicular lean mass, strength, physical performance or MyoPS in older adults at risk of sarcopenia. This trial was registered at clinicaltrials.gov as NCT03429491.


Assuntos
Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/farmacologia , Proteínas Musculares/metabolismo , Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Desempenho Físico Funcional , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Biomarcadores , Composição Corporal , Método Duplo-Cego , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Proteínas Musculares/genética , Estado Nutricional
20.
Aten Primaria ; 53(3): 101941, 2021 03.
Artigo em Espanhol | MEDLINE | ID: mdl-33592535

RESUMO

OBJECTIVE: To analyze the role of Family and Community Care Trainig Units as facilitators of the implementation of Clinical Practice Guidelines (CPG) and the factors associated with a greater effort in this task. MATERIAL AND METHODS: Design: Cross-sectional descriptive study with analytical approach. PARTICIPANTS: Training Units in Spain (N=94). MAIN MEASUREMENTS: Variables were collected through a self-completed survey into five domains: characteristics of Training Units, training activity directed at evidence-based clinical practice (EBPP), importance attributed to this activity, responsibility for EBPP implementation, perception of barriers and facilitators to its use. Descriptive and multivariate analysis with the dependent variable being the perceived effort of the training unit to implement CPG. RESULTS: 45 Training Units responded (47.9%). 42.2%(CI 95%: 27.8-56.6) of their coordinators have directed research projects and 31.1% (CI 95%:17.6-44.6) have participated in elaborating CPG. They organized an average of 51hours (SD 47.2) of training in PCBP. 97.7% (CI95%:93.3-100) considered it fundamental that the residents ow and apply PCBP and 93.3% (CI95%:86.0-100) considered that tutors are responsible for the implementation. The participation of the coordinator in CPG (coef: 0.58; IC 95%: 0.00-1.16), awareness of how important is that residents know about CPG (coef: 0.89; IC 95%: 0.24-1.54) and that CPG appear to be widely applicable. applicable (coef: 0.35; IC 95%: -0.01-0.70) were related to a greater effort by the training units. CONCLUSIONS: The training units recognize the importance of CPGs and consider that tutors are responsible for their implementation. Training Units effort to implement CPG was related to unit coordinators previous experience, the perception of applicability and residents needs.


Assuntos
Educação em Saúde , Estudos Transversais , Humanos , Espanha , Inquéritos e Questionários
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