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1.
Behav Sci Law ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39117993

RESUMO

Bullying remains a pervasive issue in educational settings worldwide. This study examined the effect of teacher training and self-efficacy on teachers' responses to school bullying with the moderating effect of age. Drawing on data from 585 Taiwanese primary and secondary school teachers, the study revealed six distinct response patterns to bullying among Taiwanese teachers. The results underscore the critical role of self-efficacy in enabling proactive responses to bullying, highlighting that training programs that boost teachers' self-efficacy can be effective across different age groups. Furthermore, the research points to the necessity of differentiated training approaches that consider teachers' age to enhance responses of mediating involvers. This study contributes to the broader discourse on bullying prevention, emphasizing the importance of teacher training and the need for further research into the nuanced relationships between teacher characteristics, self-efficacy, and intervention strategies in diverse cultural settings.

2.
Breast Cancer Res Treat ; 198(1): 113-122, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36586037

RESUMO

PURPOSE: Trastuzumab, a potent anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody, is conditionally reimbursed by the Taiwan National Health Insurance (NHI) for HER2-positive breast cancer (BC). Trastuzumab-induced cardiotoxicity studies have well characterized heart failure (HF) but fewer addressed arrhythmia, particularly the association of potential life threatening atrial fibrillation (Af) is poorly characterized. We aimed to study the trastuzumab-related risk of Af and HF using the claimed data of Taiwan NHI. METHODS: A nationwide retrospective cohort of patients with BC from the Taiwan NHI reimbursement database from January 2007 to December 2016 was analyzed. Propensity score matching and competing risk model analysis were used for adjusting confounding concurrent medication or comorbidities and competing events. The HF study was used to validate the method used. RESULTS: For Af, 12,472 trastuzumab users were matched with 12,472 non-trastuzumab users. For HF, 12,241 trastuzumab users and 12,241 non-users were enrolled. We found that trastuzumab users had significantly worse HF-free survival but not Af-free survival than non-trastuzumab users. In the competing risk analysis, the use of trastuzumab did not increase the risk of Af (hazard ratio [HR] 0.76, P = 0.0006) but was associated with HF (HR 1.19, P = 0.0052). The risk trends among stratifications by comorbidities and concurrent medication remained in similar directions for both Af and HF. CONCLUSION: Trastuzumab in real-world practice was associated with an increased risk of HF, but was not associated with an increased risk of Af in BC patients. Trastuzumab-induced arrhythmogenic effects may be masked by concurrent heart-protecting measures, more prominent roles of comorbidities or concurrent medications under real-world settings. Further studies are required.


Assuntos
Fibrilação Atrial , Neoplasias da Mama , Insuficiência Cardíaca , Humanos , Feminino , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Trastuzumab/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Estudos Retrospectivos , Pontuação de Propensão , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/epidemiologia , Medição de Risco
3.
Lung ; 201(2): 111-118, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36879087

RESUMO

PURPOSE: We evaluated gefapixant, a P2X3 receptor antagonist, in participants with recent-onset (≤ 12 months) refractory chronic cough (RCC) or unexplained chronic cough (UCC). METHODS: Participants (≥ 18 years of age; ≥ 40 mm on a 100-mm cough severity visual analog scale [VAS] at screening and randomization) with chronic cough for < 12 months were enrolled in this phase 3b, double-blind, placebo-controlled, parallel group, multicenter study (NCT04193202). Participants were randomized 1:1 to gefapixant 45 mg BID or placebo for 12 weeks with a 2-week follow-up. The primary efficacy endpoint was change from baseline at Week 12 in Leicester Cough Questionnaire (LCQ) total score. Adverse events were monitored and evaluated. RESULTS: There were 415 participants randomized and treated (mean age 52.5 years; median [range] duration 7.5 [1-12] months): 209 received placebo and 206 received gefapixant 45 mg BID. A statistically significant treatment difference of 0.75 (95% CI: 0.06, 1.44; p = 0.034) for gefapixant vs. placebo was observed for change from baseline in LCQ total score at Week 12. The most common AE was dysgeusia (32% gefapixant vs. 3% placebo participants); serious AEs were rare (1.5% gefapixant vs. 1.9% placebo participants). CONCLUSION: Gefapixant 45 mg BID demonstrated significantly greater improvement in cough-specific health status from baseline compared to placebo, in participants with recent-onset chronic cough. The most common AEs were related to taste and serious AEs were rare.


Assuntos
Tosse , Pirimidinas , Humanos , Pessoa de Meia-Idade , Tosse/tratamento farmacológico , Doença Crônica , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Método Duplo-Cego , Resultado do Tratamento
4.
Invest New Drugs ; 40(4): 789-797, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35477812

RESUMO

Lenvatinib, a multi-tyrosine kinase inhibitor that inhibits vascular endothelial growth factor and fibroblast growth factor receptors pathway, activated the immune response in tumor microenvironment. However, the combination of lenvatinib and anti-PD-1 has been reported in early phase studies. Hence, this study aims to explore the efficacy and toxicity of lenvatinib combined with nivolumab in the real-world setting. Advanced HCC patients who underwent lenvatinib combined with nivolumab (L + N group) treatment at Taipei Veterans General Hospital (Taipei, Taiwan) were reviewed between January 2016 and December 2020. Treatment response and outcomes were collected and analyzed. A control group with lenvatinib (L group) was also included for comparison. Forty patients were included in L + N group and 47 in L group. The L + N group demonstrated a higher objective response rate than L group (45.0% vs. 23.4%, p = 0.03). The L + N group also achieved longer PFS (7.5 vs. 4.8 months, p = 0.05) and OS (22.9 vs. 10.3 months, p = 0.01) than L group. Patients with HBV infection and REFLECT criteria fit demonstrated a trend of better prognosis. The PFS for those with PR, SD and PD groups were 11.2, 6.4, and 2.2 months and OS were non-reached, 14.6 and 4.7 months, respectively. Portal vein thrombosis (HR 4.3, 95% C.I. 1.5-12.8) and AFP > 400 ng/mL (HR 3.3, 95% C.I. 1.1-9.3) were poor prognostic factors and nivolumab used remained a protective factor (HR 0.2, 95% C.I. 0.1-0.7). Dermatitis (35.0%), pruritis (27.5%), and hypothyroidism (27.5%) were the common toxicities. Few patients developed grade 3/4 toxicities, including dermatitis (15%), gastrointestinal bleeding (7.5%), hypertension (5.0%), pneumonitis (2.5%) and stomatitis (2.5%). This is the first real-world data reporting the promising efficacy and tolerable toxicities of lenvatinib combined with nivolumab in advanced HCC. Further randomized trials are prompted.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Dermatite/etiologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Nivolumabe/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Quinolinas/efeitos adversos , Quinolinas/uso terapêutico , Microambiente Tumoral
5.
BMC Public Health ; 22(1): 1486, 2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927651

RESUMO

BACKGROUND: Truck drivers have difficulties participating in health education programs delivered at a fixed time and place due to the mobility of their workplace. Interventions conducted via social media can overcome these limitations of time and place. This study aimed to investigate the effect of a nutrition education intervention program delivered via a social media platform on the healthy eating behaviors of truck drivers. METHODS: This study adopted a quasi-experimental design. A 12-week intervention program was conducted for a social-media group (n = 125) and a conventional-teaching group (n = 117) from February to May 2020. The social-media group participated in a social-media-based health intervention on the LINE application. The intervention involved the provision of online messages, online instant responses, a picture-based food log, an audio e-book, and a loyalty e-card. The conventional-teaching group participated in a healthy diet course and a hygiene education manual. The generalized estimation equation (GEE) was applied to evaluate the intervention effects on the outcome measures derived from the Health Belief Model. RESULTS: The results of the GEE showed the social-media-based intervention strategies significantly decreased perceived barriers of consuming a healthy diet (p = < 0.001), increased willingness to follow cues of action (p = 0.036), improved the self-efficacy of healthy eating behaviors (p = 0.001), and increased the score of healthy eating behaviors (p < 0.001) compared with the conventional teaching strategies. For the social-media and conventional-teaching groups, no significant changes occurred in self-perceived health status, self-perceived susceptibility, or self-perceived severity after the intervention. More than 90% of the participants in the social-media group believed the social-media-based intervention strategies could help implement and maintain healthy eating behaviors. CONCLUSIONS: The results indicate social-media-based intervention strategies can facilitate approaching a population without a fixed workplace, such as truck drivers. Health promoters and planners focusing on occupational health can consider developing social-media-based intervention strategies for improving truck drivers' health status.


Assuntos
Veículos Automotores , Mídias Sociais , Dieta Saudável , Comportamento Alimentar , Humanos , Projetos de Pesquisa
6.
Am J Occup Ther ; 76(4)2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35727642

RESUMO

IMPORTANCE: Psychometric examinations for patients with stroke remain insufficient. The Center for Epidemiologic Studies Depression Scale (CES-D), Beck Depression Inventory-II (BDI-II), and Geriatric Depression Scale (GDS) are promising outcome measures. OBJECTIVE: To examine and compare the reliability and validity of three depression measures in a sample of patients with stroke. DESIGN: Repeated-measures design. SETTING: A hospital in southern Taiwan. PARTICIPANTS: Fifty-nine outpatients, who completed three depression measures. OUTCOMES AND MEASURES: Cronbach's α and intraclass correlation coefficients (ICCs) were used to examine the internal consistency and test-retest reliability, respectively, of the three measures. An independent-samples t test was conducted to compare two groups of patients with different levels of disability to investigate discriminative validity. Pearson's rs were calculated among the three measures to examine concurrent validity. RESULTS: The three measures had good internal consistency (α = .85-.92) and sufficient test-retest reliability (ICC = .84-.91). The minimal detectable change (percentage of minimal detectable change) was 10.6 (63.3%), 13.5 (98.3%), and 5.8 (49.9%) for the CES-D, BDI-II, and GDS, respectively. There was a statistically significant difference between the two groups in CES-D score (p = .032) and no significant differences on the other two measures (p = .095-.187). The correlations among the three measures ranged from .79 to .89. CONCLUSION AND RELEVANCE: All three depression measures had sound internal consistency, test-retest reliability, and concurrent validity in patients with stroke. What This Article Adds: Of the three measures, the CES-D had better discriminative validity, and the GDS demonstrated greater reliability and smaller random measurement error in patients with stroke.


Assuntos
Depressão , Acidente Vascular Cerebral , Idoso , Depressão/diagnóstico , Humanos , Psicometria , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/complicações , Inquéritos e Questionários , Taiwan
7.
Lung ; 199(2): 121-129, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33825965

RESUMO

PURPOSE: This analysis assesses clinical characteristics of patients with refractory chronic cough (RCC) or unexplained chronic cough (UCC) enrolled in a phase 2 study to better understand this patient population. METHODS: Patients with RCC/UCC lasting for ≥ 1 year and cough severity visual analog scale (VAS) score of > 40 mm at screening were eligible. Demographics, clinical characteristics, and medical history were collected at baseline. Cough-related measures included cough severity VAS, Cough Severity Diary (CSD), Leicester Cough Questionnaire (LCQ), and a structured cough-trigger questionnaire. Medication history included all medications 30 days before screening and chronic cough treatments within 1 year before screening. Data were summarized using descriptive statistics. RESULTS: Patients (N = 253; female, 76%; mean age, 60 years) had severe (mean cough severity VAS, 57.5 mm) and long-lasting (median duration, 11 years) cough. The most burdensome self-reported aspects included psychological and social factors (LCQ) and cough frequency and intensity (CSD). Patient-reported triggers were consistent with cough hypersensitivity (e.g., 95% to 96% reported irritation or tickle in throat). Common reported comorbidities included gastroesophageal reflux disease (GERD; 56%), allergic rhinitis (47%), and asthma (30%); 12% of patients had been diagnosed with all 3 conditions. The most common prior medications included inhaled or oral steroids (21%), antihistamines (15%), and antacids (15%). CONCLUSION: Patients with RCC/UCC had severe, long-lasting, and burdensome cough with clinical features of cough hypersensitivity. Many patients had been diagnosed with GERD, allergic rhinitis, and asthma but had a persistent cough despite treatment of these conditions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02612610; registered November 20, 2015.


Assuntos
Tosse/epidemiologia , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Asma/complicações , Doença Crônica , Tosse/psicologia , Tosse/terapia , Feminino , Refluxo Gastroesofágico/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Rinite Alérgica/complicações , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto Jovem
8.
BMC Med Res Methodol ; 20(1): 218, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854619

RESUMO

BACKGROUND: The data from immuno-oncology (IO) therapy trials often show delayed effects, cure rate, crossing hazards, or some mixture of these phenomena. Thus, the proportional hazards (PH) assumption is often violated such that the commonly used log-rank test can be very underpowered. In these trials, the conventional hazard ratio for describing the treatment effect may not be a good estimand due to the lack of an easily understandable interpretation. To overcome this challenge, restricted mean survival time (RMST) has been strongly recommended for survival analysis in clinical literature due to its independence of the PH assumption as well as a more clinically meaningful interpretation. The RMST also aligns well with the estimand associated with the analysis from the recommendation in ICH E-9 (R1), and the test/estimation coherency. Currently, the Kaplan Meier (KM) curve is commonly applied to RMST related analyses. Due to some drawbacks of the KM approach such as the limitation in extrapolating to time points beyond the follow-up time, and the large variance at time points with small numbers of events, the RMST may be hindered. METHODS: The dynamic RMST curve using a mixture model is proposed in this paper to fully enhance the RMST method for survival analysis in clinical trials. It is constructed that the RMST difference or ratio is computed over a range of values to the restriction time τ which traces out an evolving treatment effect profile over time. RESULTS: This new dynamic RMST curve overcomes the drawbacks from the KM approach. The good performance of this proposal is illustrated through three real examples. CONCLUSIONS: The RMST provides a clinically meaningful and easily interpretable measure for survival clinical trials. The proposed dynamic RMST approach provides a useful tool for assessing treatment effect over different time frames for survival clinical trials. This dynamic RMST curve also allows ones for checking whether the follow-up time for a study is long enough to demonstrate a treatment difference. The prediction feature of the dynamic RMST analysis may be used for determining an appropriate time point for an interim analysis, and the data monitoring committee (DMC) can use this evaluation tool for study recommendation.


Assuntos
Imunoterapia , Humanos , Modelos de Riscos Proporcionais , Análise de Sobrevida , Taxa de Sobrevida , Resultado do Tratamento
9.
BMC Public Health ; 20(1): 1639, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33138800

RESUMO

BACKGROUND: Extracurricular sport participation and exercise (ESPE) refers to regular exercise/sport participation in addition to the physical education in school among a school-aged population. Rather than general physical activity, ESPE is typically deliberately initiated and presents an efficient target for interventions. However, compared to physical activity, relatively few studies have investigated sex differences in the development of and factors associated with ESPE using a person-centered approach. This study aimed to examine the latent trajectories of ESPE from childhood to emerging adulthood across sexes, and to identify the associated sex-specific individual (i.e., body mass index, body dissatisfaction, stress, and screen behavior) and parental (i.e., parental exercise and parental screen behavior) factors. METHODS: This study used data from part of the Child and Adolescent Behavior in Long-term Evolution (CABLE) project, which comprised 2072 fourth graders (aged 9 years) in Northern Taiwan followed annually from 2001 to 2013 (13 waves). Repeated-measures latent class analysis was used to identify the trajectories of ESPE for males and females, respectively. Multinomial logistic regression was further used to identify sex-specific factors related to ESPE. RESULTS: Four trajectories of ESPE were identified for males and females. For males, these trajectories were Rarely-to-Never (20%), Often-to-Rarely (32%), Always-to-Never (21%), and Always (27%). For females, these trajectories were Rarely-to-Never (34%), Rarely (23%), Always-to-Rarely (33%), and Always (10%). We observed that the developmental patterns of ESPE varied by sex such that there was an earlier decline in the trajectories of ESPE in females than in males and that, compared with males, fewer females maintained exercise habits in young adulthood. Furthermore, we found several sex-specific factors related to ESPE, namely, stress, BMI, and parental exercise. Body dissatisfaction and individual screen behavior were associated with trajectories of ESPE for both sexes. CONCLUSIONS: We found distinct trajectories of ESPE from childhood to emerging adulthood for both sexes. The trajectories of ESPE for males and females, however, differ in terms of patterns and associated factors. Our findings suggest that efforts to increase ESPE should be initiated early, and may be made more effective by considering sex differences.


Assuntos
Caracteres Sexuais , Esportes , Adolescente , Adulto , Criança , Estudos de Coortes , Exercício Físico , Feminino , Humanos , Estudos Longitudinais , Masculino , Taiwan/epidemiologia , Adulto Jovem
10.
BMC Pediatr ; 20(1): 221, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414349

RESUMO

BACKGROUND: Relatively few studies have investigated the effects of diet on behavior problems among preschoolers, particularly, physical aggression. In addition, children raised by poorly educated mothers usually have a higher probability of developing negative outcomes. Additionally, highly educated mothers have a higher probability of providing more healthy foods for their children. Thus, mothers providing healthy foods might mitigate children's behavior problems. The study aims to examine whether preschoolers' dietary pattern, as a manipulable factor, mediates the association between maternal education level and physical aggression. METHODS: Data came from the Taiwan Birth Cohort Study (TBCS), a nationally representative population-based cohort study, which included 18,513 five-year-old Taiwanese children. Mothers and primary caregivers reported the information on preschoolers' physical aggression and food consumption at age 5 and maternal education level at age 6 months. Two dietary patterns, namely a healthy diet and a high-fat-sugar-salt (HFSS) diet, were retrieved by exploratory factor analysis. Mediation hypotheses were tested by a series of multiple regression models conducted using the PROCESS macro of SAS 9.4. All models were adjusted for children's sex, parental marital status, household income, mental distress at age 5 and children's physical aggression at age 3. RESULTS: Maternal education positively linked to healthy dietary patterns (B = 0.014, p = 0.002) which was negatively associated with preschoolers' physical aggression (B = -0.096, p = 0.013), and it is negatively related to the HFSS dietary pattern (B = -0.042, p = 0.002) which was directly positively associated with preschoolers' physical aggression (B = 0.123, p = 0.008). The association between maternal education and preschoolers' physical aggression was partially mediated by preschoolers' healthy (B = -0.001, p < .001) and HFSS (B = -0.005, p = <.001) dietary patterns, respectively. The R-square of the mediation model is 0.178. CONCLUSIONS: Preschoolers' dietary patterns directly associate with their physical aggression. In addition, mothers with poor education may provide less healthy foods and more unhealthy foods to their children, which may increase the level of physical aggression. The results imply partial mediating effects of dietary patterns between maternal education and physical aggression. It is suggested that a parent-based nutritional education program focusing on healthy meal preparation for poor educated mothers might be beneficial for preschoolers' healthy development.


Assuntos
Agressão , Mães , Criança , Pré-Escolar , Estudos de Coortes , Escolaridade , Feminino , Humanos , Lactente , Taiwan
11.
J Formos Med Assoc ; 119(8): 1274-1282, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31787488

RESUMO

BACKGROUND/PURPOSE: We examined the prevalence of probable common mental disorders (CMDs) in commercial low-dose computed tomography (LDCT) lung cancer screening consumers relative to the general population and to determine the correlates of probable CMDs among screening participants. METHODS: Commercial LDCT lung cancer screening consumers (N = 1323) were compared with a nationally representative sample from the Taiwan Social Change Survey (TSCS) (N = 2034). Respondents scoring ≥3 on the Chinese Health Questionnaire were classified as having a probable CMD. Logistic regression was used to investigate differences between the two groups and correlates of probable CMDs among LDCT lung cancer screening participants. RESULTS: The prevalence of probable CMDs was higher among LDCT lung cancer screening participants (25.47%) than among TSCS adults (21.56%). Compared with the TSCS sample, the screening participants had a higher probability of CMDs (OR = 1.40, 95% CI = 1.13-1.73), higher education levels (OR = 7.95, 95% CI = 6.00-10.53), and a history of drinking (OR = 11.85, 95% CI = 9.45-14.85) or betel-quid use (OR = 5.43, 95% CI = 3.98-7.42) but were less likely to smoke (OR = 0.52, 95% CI = 0.40-0.68). Among the screening participants, being female (OR = 1.37, 95% CI = 1.02-1.84) and a current smoker (OR = 1.74, 1.19-2.54) and living near ≥2 smoking family members (OR = 2.30, 95% CI 1.57-3.38) were associated with an increased likelihood of having CMDs. CONCLUSION: Commercial LDCT lung cancer screening users may have a positive association with probable CMDs compared to the general population. Screening programs should consider including criteria and providing psychoeducation to improve the physical and mental outcomes of participants. CLINICAL TRIAL REGISTRATION: Purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) do not require registration.


Assuntos
Neoplasias Pulmonares , Transtornos Mentais , Adulto , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Transtornos Mentais/epidemiologia , Fatores de Risco , Taiwan/epidemiologia
12.
J Youth Adolesc ; 49(9): 1897-1912, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32323094

RESUMO

Research indicates that externalizing and internalizing pathways emanated in childhood are connected to later drinking behaviors; however, no study has investigated the contemporaneous effects of the two pathways using a person-centered approach that categorizes individuals based on their various developmental patterns. This study examined the distinct patterns of concurrent development of aggression and depressive symptoms in childhood and their associations with later drinking behaviors using data from a 15-year Taiwanese cohort since age 8 (N = 2854, 49% females). Group-based multi-trajectory modeling identified four aggressive-depressive trajectory groups: Moderate, Aggressive, Depressive, and Comorbid, which manifested a sequential risk gradient in alcohol use. Comorbid group, characterized by persistently high levels of aggression and depressive symptoms, has the highest levels of alcohol use and drinking problems and the earliest onset of drinking. Aggressive and Depressive groups have higher levels of alcohol use and earlier onset of drinking than Moderate group. These findings imply the importance of monitoring aggression and depressive symptoms simultaneously and continually in childhood to prevent later drinking.


Assuntos
Agressão , Alcoolismo , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Criança , Estudos de Coortes , Comorbidade , Feminino , Humanos , Estudos Longitudinais , Masculino
13.
Eur Respir J ; 54(1)2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31023843

RESUMO

We evaluated the effect of gefapixant on cough reflex sensitivity to evoked tussive challenge.In this phase 2, double-blind, two-period study, patients with chronic cough (CC) and healthy volunteers (HV) were randomised to single-dose gefapixant 100 mg or placebo in a crossover fashion. Sequential inhalational challenges with ATP, citric acid, capsaicin and distilled water were performed 1, 3 and 5 h after dosing. Mean concentrations evoking ≥2 coughs (C2) and ≥5 coughs (C5) post dose versus baseline were co-primary endpoints. Objective cough frequency (coughs·h-1) over 24 h and a cough severity visual analogue scale (VAS) were assessed in CC patients. Adverse events were monitored.24 CC patients and 12 HV were randomised (mean age 61 and 38 years, respectively). The cough challenge threshold increased for ATP by 4.7-fold (C2, p≤0.001) and 3.7-fold (C5, p=0.007) for gefapixant versus placebo in CC patients; in HV, C2 and C5 increased 2.4-fold (C2, p=0.113; C5, p=0.003). The distilled water C2 and C5 thresholds increased significantly (p<0.001) by a factor of 1.4 and 1.3, respectively, in CC patients. Gefapixant had no effect on capsaicin or citric acid challenge. Median cough frequency was reduced by 42% and the least squares mean cough severity VAS was 18.0 mm lower for gefapixant versus placebo in CC patients. Dysgeusia was the most frequent adverse event (75% of HV and 67% of CC patients).ATP-evoked cough was significantly inhibited by gefapixant 100 mg, demonstrating peripheral target engagement. Cough count and severity were reduced in CC patients. Distilled water may also evoke cough through a purinergic pathway.


Assuntos
Tosse/tratamento farmacológico , Tosse/fisiopatologia , Antagonistas do Receptor Purinérgico P2X/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Antitussígenos/efeitos adversos , Antitussígenos/uso terapêutico , Testes de Provocação Brônquica , Doença Crônica , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas do Receptor Purinérgico P2X/efeitos adversos , Pirimidinas/efeitos adversos , Sulfonamidas/efeitos adversos , Reino Unido , Escala Visual Analógica
14.
J Immunol ; 195(7): 3284-92, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26297760

RESUMO

Impaired T cell responses are a defining characteristic of HIV infection, but the extent to which altered mononuclear phagocyte function contributes to this defect is unclear. We show that mononuclear phagocytes enriched from rhesus macaque lymph nodes have suppressed ability to stimulate CD4 T cell proliferation and IFN-γ release after acute SIV infection. When individual populations were isolated, myeloid dendritic cells (mDC) and macrophages but not plasmacytoid DC (pDC) had suppressed capacity to stimulate CD4 T cell proliferation, with macrophage function declining as infection progressed. Macrophages, but not pDC or mDC, had suppressed capacity to induce IFN-γ release from CD4 T cells in acute infection, even after stimulation with virus-encoded TLR7/8 ligand. Changes in expression of costimulatory molecules did not explain loss of function postinfection. Conversely, pDC and mDC had marked loss of IFN-α and IL-12 production, respectively, and macrophages lost production of both cytokines. In T cell cocultures without TLR7/8 ligand, macrophages were the primary source of IL-12, which was profoundly suppressed postinfection and correlated with loss of IFN-γ release by T cells. TLR7/8-stimulated pDC, mDC and macrophages all produced IL-12 in T cell cocultures, which was suppressed in chronic infection. Supplementing IL-12 enhanced mDC-driven IFN-γ release from T cells, and IL-12 and IFN-α together restored function in TLR7/8-activated macrophages. These findings reveal loss of macrophage and mDC T cell-stimulating function in lymph nodes of SIV-infected rhesus macaques associated with diminished IL-12 and IFN-α production that may be a factor in AIDS immunopathogenesis.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Ativação Linfocitária/imunologia , Macrófagos/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Animais , Proliferação de Células , Interferon-alfa/biossíntese , Interleucina-12/biossíntese , Linfonodos/citologia , Linfonodos/imunologia , Macaca mulatta , Masculino , Fagocitose/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/patologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/imunologia , Receptor 7 Toll-Like/imunologia , Receptor 8 Toll-Like/imunologia
15.
Acta Paediatr ; 106(6): 984-990, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28150460

RESUMO

AIM: Excessive television (TV) exposure has negative impacts on a child's development, health and behaviour. This study examined the under-researched area of what impact infant and parental TV viewing during a child's infancy had on the child's later viewing habits. METHODS: Data on 18 577 babies born in 2005 were collected from the Taiwan Birth Cohort Study, a prospective longitudinal study of a nationally representative cohort. Group-based trajectory analysis was conducted to identify childhood TV viewing trajectories at 18, 36 and 66 months of age. Multinomial logistic regression was used to examine the influence of parents' TV behaviour on their children's TV viewing trajectories. RESULTS: The percentage of children falling into the TV viewing trajectories that were identified were low (20%), increasing (46.5%) and high (33.5%). The child's TV viewing trajectory was significantly associated with the child's sex, parent's monthly household income, child's day care arrangements, maternal and paternal education, maternal and paternal TV viewing time and whether the child's TV viewing time was restricted. CONCLUSION: The amount of TV that children watched when they were older was associated with a range of factors, and the results particularly highlight the need to restrict child and parental viewing time in infancy.


Assuntos
Hábitos , Televisão/estatística & dados numéricos , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pais/psicologia
16.
Arch Phys Med Rehabil ; 97(11): 1917-1923, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27240434

RESUMO

OBJECTIVES: To examine the test-retest reliability, calculate minimal detectable change (MDC), and report internal consistency of the Test of Visual Perceptual Skills-Third Edition (TVPS-3) in patients with stroke. DESIGN: Repeated-measures design (at an interval of 2wk). SETTING: Medical center. PARTICIPANTS: Patients (N=50) with chronic stroke who completed the TVPS-3. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: TVPS-3 that contains 7 subscales, namely, visual discrimination, visual memory, spatial relations, form constancy, sequential memory, visual figure-ground, and visual closure. RESULTS: The intraclass correlation coefficient value of the overall scale was .92 and those of the 7 subscales were .53 to .82. The MDC values of the overall scale and the subscales were 18.1 and 5.4 to 7.1, respectively. The MDC% value of the overall scale was 16.2% (<30%), showing acceptable random measurement error. However, the MDC% values of the subscales were 33.7% to 44.1% (>30%), indicating substantial random measurement errors. The Cronbach α of the 7 subscales were .71 to .89, indicating good internal consistency. CONCLUSIONS: Our results showed that the overall scale of the TVPS-3 had satisfactory test-retest reliability. However, the subscales demonstrated insufficient test-retest reliability. Therefore, the subscales should be used cautiously to explain the test results over repeated assessments in patients with stroke.


Assuntos
Modalidades de Fisioterapia , Reabilitação do Acidente Vascular Cerebral/métodos , Testes Visuais , Percepção Visual , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
17.
Public Health Nutr ; 19(9): 1654-65, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26781068

RESUMO

OBJECTIVE: To investigate the reciprocal relationship between unhealthy eating behaviours and depressive symptoms from childhood to adolescence. DESIGN: Unhealthy eating behaviours were measured by the frequencies of eating foods with excess salt, sugar or fat in the past week. Depressive symptoms in the past two weeks were measured using a seven-item scale. Hierarchical linear growth models were used to analyse longitudinal associations between unhealthy eating behaviours and depressive symptoms. Time-fixed variables (sex, parents' education level and household monthly income) and time-varying variables (parents' marital status, family activities, body weight, vegetable or fruit consumption, exercising and smoking) were controlled for. SETTING: The Child and Adolescent Behaviors in Long-Term Evolution study, which commenced in 2001 and has annual follow-up. SUBJECTS: Students (n 2630) followed from 2nd grade (8 years old in 2002) to 11th grade. RESULTS: The frequency of unhealthy eating behaviours in the previous year and the difference between the frequency in the previous and successive year were positively associated with the initiation and growth rate of depressive symptoms. Depressive symptoms in the previous year and the difference in depressive symptoms between the previous and successive year were positively associated with the initial state and growth rate of unhealthy eating behaviours. CONCLUSIONS: Our results suggest a reciprocal relationship between depressive symptoms and unhealthy eating behaviours. This relationship should be considered when developing programmes targeting depressive symptoms and unhealthy diet in children and adolescents.


Assuntos
Comportamento do Adolescente , Comportamento Infantil , Depressão/epidemiologia , Dieta , Comportamento Alimentar , Adolescente , Criança , Feminino , Seguimentos , Humanos , Masculino
18.
BMC Public Health ; 16(1): 1066, 2016 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-27724881

RESUMO

BACKGROUND: Students should be encouraged to help prevent or stop bullying. However, defending victims of bullying can impact on mental health. It is not only bystanders who may defend victims, but bullies, victims and bully-victims can also have defending behaviors. Nevertheless, most studies of defending behaviors have been limited to an examination of the reactions of bystanders or those not involved in bullying and have ignored the other players. The aim of this study is to investigate the associations between defending behaviors and mental health among bullies, victims, bully-victims and bystanders. METHODS: Associations among defending behaviors, mental health (including depressive symptoms and social anxiety), and bullying experiences were cross-sectionally examined in 3441 students (13-15 years old.) from 20 randomly selected junior high schools in Taiwan using a self-report questionnaire. SAS 9.3 Survey Analysis procedures were used to conduct descriptive analysis and multiple regression models. RESULTS: Defending behaviors were associated with bullying roles and were higher in victims than in bullies or bystanders. Defending behaviors were positively associated with social anxiety and depressive symptoms. After stratifying by bullying roles, defending behaviors were positively associated with social anxiety in bystanders, and were positively associated with depressive symptoms in victims and bystanders. However, defending behaviors were not significantly associated with mental health indicators in bullies. CONCLUSIONS: The associations between defending behaviors and mental health varied according to bullying roles. The results suggest that bystanders and victims experience more mental health effects than bullies. Intervention programs aimed at preventing bullying should focus on strategies that minimize social anxiety and depression in victims and bystanders, and urge students to help vulnerable peers during bullying events.


Assuntos
Comportamento do Adolescente/psicologia , Bullying , Vítimas de Crime/psicologia , Transtornos Mentais/psicologia , Estudantes/psicologia , Adolescente , Estudos Transversais , Depressão/psicologia , Feminino , Humanos , Masculino , Grupo Associado , Fobia Social/psicologia , Análise de Regressão , Instituições Acadêmicas , Inquéritos e Questionários , Taiwan
20.
Ann Surg Oncol ; 22(13): 4402-10, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25905586

RESUMO

PURPOSE: Autophagy is a cell survival mechanism that plays a critical role in pancreatic carcinogenesis. Murine studies have previously demonstrated that treatment with the late-autophagy inhibitor chloroquine in combination with chemotherapy limited tumor growth. METHODS: In this phase 1/2 trial, we examined treatment with hydroxychloroquine (HCQ) and gemcitabine for patients with pancreatic adenocarcinoma. The primary endpoints were safety and tolerability, evaluated by Storer's dose escalation design. Secondary endpoints were CA 19-9 biomarker response, R0 resection rates, survival, and correlative studies of autophagy. RESULTS: Thirty-five patients were enrolled. There were no dose-limiting toxicities and no grade 4/5 events related to treatment. Nineteen patients (61 %) had a decrease in CA 19-9 after treatment. Twenty-nine patients (94 %) underwent surgical resection as scheduled, with a 77 % R0 resection rate. Median overall survival was 34.8 months (95 % confidence interval, 11.57 to not reached). Patients who had more than a 51 % increase in the autophagy marker LC3-II in circulating peripheral blood mononuclear cells had improvement in disease-free survival (15.03 vs. 6.9 months, p < 0.05) and overall survival (34.83 vs. 10.83 months, p < 0.05). No outcome differences were demonstrated in the 81 % of patients with abnormal p53 expression assessed by immunohistochemistry in the resected specimens. CONCLUSIONS: Preoperative autophagy inhibition with HCQ plus gemcitabine is safe and well tolerated. Surrogate biomarker responses (CA 19-9) and surgical oncologic outcomes were encouraging. p53 status was not associated with adverse outcomes.


Assuntos
Adenocarcinoma/tratamento farmacológico , Autofagia/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Hidroxicloroquina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Antirreumáticos/uso terapêutico , Biomarcadores/metabolismo , Antígeno CA-19-9/metabolismo , Desoxicitidina/uso terapêutico , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Prospectivos , Segurança , Taxa de Sobrevida , Gencitabina , Neoplasias Pancreáticas
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