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PURPOSE: Earlier studies suggest progression-free survival (PFS) may be used as a surrogate endpoint for overall survival (OS) in metastatic breast cancer, which could shorten follow-up duration and speed up assessment of treatment effects. However, to our knowledge, the association between them is still unclear in advanced or metastatic triple-negative breast cancer (TNBC). METHODS: A literature-based meta-analysis followed by correlation analysis was conducted in advanced or metastatic TNBC. Weighted multiple regression analysis was then used to test the strength of the association between medians of PFS and OS, and the association between HRPFS and HROS. RESULTS: Fourteen randomized clinical trials published between January 2007 and August 2019, 31 median pairs for PFS and OS, and 17 pairs for HRPFS and HROS from 3,880 patients were selected. The Pearson correlation coefficient between medians of PFS and OS was 0.84 (95% confidence interval (CI) 0.68-0.92, p < 0.001), and the correlation coefficient between HRPFS and HROS was 0.86 (95% CI 0.63-0.95, p < 0.001). Weighted multiple regression analysis showed HRPFS was the most significant predictor of HROS among covariates analyzed (p < 0.001). Both the medians of PFS and OS correlation, and the HRPFS and HROS correlation were 0.79 (p < 0.001), 0.80 (p = 0.001), respectively, in the 11 trials excluding immunotherapy and bevacizumab-based therapy trials. CONCLUSIONS: Our analysis suggests PFS can be strongly correlated with OS and considered a valid surrogate endpoint for OS in advanced or metastatic TNBC.
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Biomarcadores , Intervalo Livre de Progressão , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia , Progressão da Doença , Feminino , Humanos , Taxa de SobrevidaRESUMO
BACKGROUND: Reduction in neonatal deaths has been a major challenge globally. To prevent neonatal deaths, improvements in newborn care have been promoted worldwide. The World Health Organization Western Pacific Regional Office has been promoting the Early Essential Newborn Care (EENC), a package of specific simple and cost-effective interventions, in their region. However, mere introduction of EENC cannot reduce neonatal deaths unless quality of care is ensured. In Lao PDR, the government introduced self-managed continuous monitoring as a sustainable way to improve the quality of care described in the EENC. METHODS: A clustered randomized controlled trial was designed to compare the effectiveness of self-managed continuous monitoring with external supervisory visits to monitor health workers' satisfactory EENC performance and their knowledge and skills related to the EENC in Lao PDR. Determinants of EENC performance will be measured with a structured questionnaire developed based on the Theory of Planned Behaviour, which predicts future behaviour. During self-managed continuous monitoring activities, health workers in each district hospital will conduct periodical peer reviews and feedback sessions. Fifteen district hospitals will be randomly allocated into the self-managed continuous monitoring (intervention) and the supervision (control) groups. Fifteen health workers routinely involved in maternity and newborn care including physicians, midwives and other health staff will be recruited from each hospital (effect size 0.6, intra-cluster correlation coefficient 0.06, 5% alpha error and 80% power). We will compare the change in the mean score of the determinants before and one year after randomisation between the two groups. We will also compare the retention of knowledge and skills related to the EENC between the two groups. The expected enrolment period is July 20th, 2017 to July 20th, 2018. DISCUSSION: This is the first cluster randomized trial to evaluate a self-managed continuous monitoring system for quality maintenance of newborn care in a resource-limited country. This research is conducted in collaboration with the Ministry of Health and international organizations; therefore, if effective, this intervention would be applied in larger areas of the country and the region. TRIAL REGISTRATION: This trial was registered at UMIN-CTR on 15th of June, 2017. Registration number is UMIN000027794 .
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Pessoal de Saúde , Cuidado do Lactente/normas , Garantia da Qualidade dos Cuidados de Saúde/métodos , Análise Custo-Benefício , Atenção à Saúde/normas , Humanos , Cuidado do Lactente/economia , Recém-Nascido , Laos , Melhoria de Qualidade , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To determine the effectiveness of a personal support lifestyle education programme (PSMetS) for reducing risk factors in individuals with metabolic syndrome (MetS). DESIGN: A two-arm randomised controlled trial. SETTING: Companies in metropolitan Tokyo, Japan. SUBJECTS: Male workers with diagnosed MetS or a high risk for MetS according to the Counselling Guidance Program, Japan (n 193). RESULTS: The reduction in the number of risk factors for MetS (as defined according to the criteria published by the Japanese Ministry of Health, Labor and Welfare in April 2007 (MHLW-MetS)) in the PSMetS group was not significantly different from that in the usual care group by van Elteren's test (baseline-adjusted P=0·075) for intention-to-treat (ITT), while it was significant (baseline-adjusted P=0·038) for per-protocol set (PPS). The proportion of MHLW-MetS was significantly different between groups by van Elteren's test (baseline-adjusted P=0·031). Two components of MHLW-MetS showed significant reductions in the PSMetS group: waist circumference (baseline-adjusted P=0·001) and BMI (baseline-adjusted P=0·002). PPS and ITT analyses showed similar results. CONCLUSIONS: For male workers with MHLW-MetS or a high risk of MHLW-MetS, PSMetS reduced the number of risk factors for MHLW-MetS.
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Promoção da Saúde/métodos , Estilo de Vida , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/prevenção & controle , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Colesterol/sangue , Dislipidemias/diagnóstico , Dislipidemias/prevenção & controle , Comportamentos Relacionados com a Saúde , Educação em Saúde , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/prevenção & controle , Hipertensão/sangue , Hipertensão/diagnóstico , Japão , Masculino , Pessoa de Meia-Idade , Obesidade/prevenção & controle , Fatores de Risco , Tamanho da Amostra , Triglicerídeos/sangue , Circunferência da CinturaRESUMO
BACKGROUND: Blood alcohol concentration data that were previously obtained from 34 healthy Japanese subjects with limited sampling times were reanalyzed. Characteristics of the data were that the concentrations were obtained from only the early part of the time-concentration curve. OBJECTIVE: To explore significant covariates for the population pharmacokinetic analysis of alcohol by incorporating external data using a Bayesian method, and to estimate effects of the covariates. METHODS: The data were analyzed using a Markov chain Monte Carlo Bayesian estimation with NONMEM 7.3 (ICON Clinical Research LLC, North Wales, Pennsylvania). Informative priors were obtained from the external study. RESULTS: A 1-compartment model with Michaelis-Menten elimination was used. The typical value for the apparent volume of distribution was 49.3 L at the age of 29.4 years. Volume of distribution was estimated to be 20.4 L smaller in subjects with the ALDH2*1/*2 genotype than in subjects with the ALDH2*1/*1 genotype. CONCLUSIONS: A population pharmacokinetic model for alcohol was updated. A Bayesian approach allowed interpretation of significant covariate relationships, even if the current dataset is not informative about all parameters. This is the first study reporting an estimate of the effect of the ALDH2 genotype in a PPK model.
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OBJECTIVES: This study aimed to examine the association between subjective symptoms and lifestyle habits among junior high school students by using a cross-sectional survey. METHODS: The survey was conducted during May-November 2012. The study subjects were 1229 adolescents (527 boys and 702 girls, age 12-13 years) from 10 junior high schools in Kumamoto Prefecture, Japan. Data from 1182 students (500 boys and 682 girls; response rate 96.2%) were used for the analyses. School nurses measured students' body weights and heights. A self-administered questionnaire examining dietary intake (FFQW82), subjective symptoms (12 items), lifestyle habits (18 items), and diet- and health-related topics (9 items) was used. The 4 categories of each of the 12 subjective symptoms were classified into dichotomous variables (1=always or sometimes; 0=occasionally or never). The subjective symptom score was calculated as a total score by summing up the dichotomous variables for the 12 subjective symptoms. Associations were examined using a chi-square test, Student's t-test, Wilcoxon rank sum test, and a stepwise regression model. The structure of factors was examined by factor analysis (varimax rotation) and associations among the question items were examined by principal component analysis. A significance level of 5% (two-sided) was applied and SAS ver. 9.3 software was used for the analyses. RESULTS: Students' body weights and heights were mostly at or near national averages. The ratio of energy intake at breakfast, lunch, and dinner for the 1-day total energy intake (kcal) was respectively 2:3:4, indicating decreased energy intake at breakfast. The percent energy (%E) from fat of the 1-day total energy intake was 29%E for boys and 30%E for girls. Using regression models, we found that the following lifestyle factors were significantly related to fewer subjective symptoms: "balanced diet," and "sleeping 6 hours or more per day" were for boys and girls, "regularly eating three meals a day," "strong appetite," and "having relaxation time" for girls. However, the following factors were significantly related to more subjective symptoms: "eating hurriedly," and "2 hours or more of watching television or playing video games" were for boys and girls, "cooking meals or sweets" for boys, "eating snacks and nighttime meals," and "eating dinner after 9 p.m.," and "preparing bento (boxed lunches)" for girls. Dietary intake was not significantly related to subjective symptoms. CONCLUSION: Findings from this study suggest that subjective symptoms are associated with lifestyle habits among junior high school students.
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Comportamento Alimentar , Estilo de Vida , Adolescente , Criança , Estudos Transversais , Ingestão de Alimentos , Ingestão de Energia , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
The solution of sharing electronic health records (EHR) with patients has the potential to improve patients' understanding and remembering of their health information. We call this solution the patient open-EHR. In Japan, this solution is not yet widespread, and experiences of actual users are not known. Our aim is to explore the needs and satisfaction of patients who are actually using one patient open-EHR system in Japan that allows registered patients online access to part of their EHR. A cross-sectional study was done using an online questionnaire. Patients registered with our patient open-EHR system were invited to participate by posting an invitation message on the system login page and sending them invitation emails. We investigated their needs regarding the system and their views regarding the system's ability to improve their understanding, remembering, and other perspectives. Answers from 95 patients, collected between August 10 and October 20, 2019 were analyzed. The need to further understand and remember the information received from the doctor was among the top four reasons behind using the system. However, only 48% of patients agreed that the system improved their remembering and 68% agreed that it improved their understanding. Thirty-seven percent of respondents expressed dissatisfaction with access to only blood test results and prescriptions. Despite this dissatisfaction, respondents were positive about the future of the system. Hospitals need to recognize the needs of patients and to consider them when providing patient open-EHR service. The EHR has potential not only for hospitals but also for patients.
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Allowing patients to access their electronic health records (EHR) online, that we call the patient open- EHR, may help patients better understand and remember their health information, leading to improved health outcomes. In Japan, such solution is not yet widespread, and general patients' expectations for such solution are not known. The OpenNotes initiative in the United States of America (USA) had done various studies concerning the intervention of sharing doctors' notes, which are part of the EHR, with patients. Our study objective is to explore general patients' expectations toward potential benefits and risks of the patient open-EHR solution if given chance to use in Japan. A cross-sectional study was done using an online questionnaire. One hundred and eighty-three general patients without previous experience using the patient open-EHR service, responded to our survey after being recruited through SNS and posters at a university hospital not offering the solution. Comparison with the result of the OpenNotes original study, conducted in a similar setting, was also done. The results showed that participants were, similarly to the OpenNotes results, positive about the system's potential benefits; 90% agreed on the system ability to help them better understand their condition and remember their healthcare plan. On the other hand, they were much concerned about the potential risks especially privacy; 62% agreed they would be worried about their privacy. Adequate measures to provide highly secured systems and to allow patients to be better informed about the use of their personal health records should be taken to comfort future users.
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BACKGROUND: Many clinical trials have been conducted to verify the effects of interventions for prevention of type 2 diabetes (T2D) using different treatments and outcomes. The aim of this study was to compare the effectiveness of lifestyle modifications (LM) with other treatments in persons at high risk of T2D by a network meta-analysis (NMA). METHODS: Searches were performed of PUBMED up to January 2018 to identify randomized controlled trials. The odds ratio (OR) with onset of T2D at 1 year in the intervention group (LM, dietary, exercise, or medication) versus a control group (standard treatments or placebo) were the effect sizes. Frequentist and Bayesian NMAs were conducted. RESULTS: Forty-seven interventions and 12 treatments (20,113 participants) were used for the analyses. The OR in the LM was approximately 0.46 (95% CI: 0.33 to 0.61) times lower compared to the standard intervention by the Bayesian approach. The effects of LM compared to other treatments by indirect comparisons were not significant. CONCLUSIONS: This meta-analysis further strengthened the evidence that LM reduces the onset of T2D compared to standard and placebo interventions and appears to be at least as effective as nine other treatments in preventing T2D.
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Diabetes Mellitus Tipo 2/prevenção & controle , Estilo de Vida Saudável , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Comportamento de Redução do Risco , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Dieta Saudável , Exercício Físico , Humanos , Incidência , Metanálise em Rede , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: Self-extubation of tubes and catheters causes various adverse events in postoperative patients. We investigated preoperative risk factors associated with self-extubation. DESIGN: A matched case-control study. SETTING: Teikyo University Hospital. PARTICIPANTS: Postoperative patients over 50 years old. METHODS: Sixty-five patients with a comment in the incident report about self-extubation within 7 postoperative days were recruited for the case group. One hundred ninety-five matched patients in the control group were randomly recruited from an electronic medical record. This group was three times larger than the case group. The matching factors were age, sex, type of tube, duration of tube insertion, and year of the incident. Conditional multiple logistic regression analysis was performed. RESULTS: Sixty-five self-extubation events occurred, and constituted 6.5% of 996 postoperative incident reports. Three significant preoperative risk factors were abdominal operation (odds ratio [OR], 3.21; 95% confidence interval [95% CI], 1.05-10.83), history of dementia (OR, 10.71; 95% CI, 1.45-132.55), and preoperative hemoglobin level (OR, 0.77 per 1.0âg/dL increase; 95% CI, 0.62-0.96). CONCLUSIONS: Elderly patients with a history of dementia and low preoperative hemoglobin are at a risk of postoperative self-extubation, especially after an abdominal operation. These predictors can contribute to the more effective prevention of perioperative self-extubation.
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Extubação/métodos , Cuidados Pós-Operatórios/métodos , Cuidados Pré-Operatórios/métodos , Comportamento Autodestrutivo/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de TempoRESUMO
INTRODUCTION: Severe subjective psychosomatic symptoms (SPS) in adolescents are a major public health concern, and lifestyle modification interventions for reducing SPS are important topics. Recently, we developed a school-based lifestyle education involving parents for reducing SPS of adolescents (SPRAT), an improved version of the programme from our previous study Programme for adolescent of lifestyle education in Kumamoto (PADOK). This study aimed to evaluate the effectiveness of SPRAT in reducing SPS among adolescents. METHODS AND ANALYSIS: This is a 6-month, cluster randomised clinical trial with two intervention arms (SPRAT vs usual school education). The study population will be composed of middle school students (aged 12-14 years) with their parents/guardians in Japan. SPRAT is expected to be a more powerful programme than PADOK as it reinforces the role of parent participation. The primary endpoint will be the change from baseline SPS scores to those obtained after 6 months. Between-group differences will be analysed following the intention-to-treat principle. Crude and multivariate adjusted effects will be examined using a general linear mixed-effects model for continuous variables and a logistic regression model for dichotomous variables. The sample size required was determined based on the information needed to detect a difference in the primary outcome with a significance level of 5% and power of 80% under the assumptions of 40 students per cluster (assuming the same sample size for each cluster), an effect size of 0.3 and an intraclass correlation coefficient of 0.02. In total, participation by 28 schools (14 schools in each arm) (students: n=1120) will be needed. ETHICS AND DISSEMINATION: This study was approved by the Medical Ethical Committee of Minami Kyushu University in 2017 (number 137). The findings will be disseminated widely through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: UMIN000026715; Pre-results.
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Promoção da Saúde/métodos , Estilo de Vida , Relações Pais-Filho , Pais/educação , Transtornos Psicofisiológicos/prevenção & controle , Estudantes/psicologia , Adolescente , Comportamento do Adolescente , Criança , Feminino , Humanos , Japão , Modelos Logísticos , Masculino , Análise Multivariada , Projetos de Pesquisa , Serviços de Saúde Escolar , Instituições AcadêmicasRESUMO
BACKGROUND: It is known that beer accelerates gastrointestinal motility in humans. Our previous studies showed that beer congener stimulates gastrointestinal motility by directly stimulating the muscarinic M3 receptor. Further, we isolated 2 active compounds (compounds A and B) from beer by liquid chromatography. The objective of the present study was to identify the 2 active compounds that bind to the muscarinic M3 receptor in beer. METHODS: Structural analyses of the active compounds were performed by fast atom bombardment mass spectra, 1H-nuclear magnetic resonance (NMR), and 13C-NMR spectroscopy. Active compounds were chemically synthesized from p-coumaric acid and agmatine as starting materials. Binding activity to the muscarinic M3 receptor was used to confirm the activity of the synthetic compounds. RESULTS: It was identified that 2 active compounds had the same structural characteristics: stereoisomers (cis-isomer and trans-isomer), molecular weight=550 and molecular formula=C28H38N8O4. Trans-isomer (compound B) was identified as the known substance hordatine A, a kind of phytoalexin in barley, and cis-isomer (compound A) was found to be a novel compound (tentatively referred to as aperidine). Both naturally present and chemically synthesized aperidine (compound A) and hordatine A (compound B) were demonstrated to have potent binding activities to the muscarinic M3 receptor. CONCLUSIONS: The 2 active compounds isolated from beer, namely aperidine (compound A) and hordatine A (compound B), have structurally and functionally been identified as active entities of binding to the muscarinic M3 receptor.
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Cerveja/análise , Benzofuranos/isolamento & purificação , Guanidinas/isolamento & purificação , Receptor Muscarínico M3/efeitos dos fármacos , Terpenos/isolamento & purificação , Animais , Benzofuranos/síntese química , Benzofuranos/farmacologia , Células CHO , Cricetinae , Cricetulus , Motilidade Gastrointestinal/efeitos dos fármacos , Guanidinas/síntese química , Guanidinas/farmacologia , Espectroscopia de Ressonância Magnética , Peso Molecular , Sesquiterpenos , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Estereoisomerismo , Relação Estrutura-Atividade , Terpenos/síntese química , Terpenos/farmacologia , FitoalexinasRESUMO
INTRODUCTION: Hoarding disorder can cause problems with work performance, personal hygiene, health and well-being. The disorder is a growing social problem in Japan. Having difficulty discarding rubbish, decluttering and organising can signal a future hoarding disorder, and early intervention is important. We developed an educational workshop on decluttering and organising for teens and adults with difficulty organising. The objective of this study is to evaluate the effectiveness of a workshop for reducing clutter and improving quality of life among younger people with difficulty decluttering and organising. METHODS AND ANALYSIS: An open-label, parallel-group, randomised controlled trial will be conducted among volunteers aged 12-55 years with mild difficulty decluttering and organising. Those in the intervention group will attend the workshop and receive a visit from a professional cleaning company to declutter their living space. The control group will have only the latter. The primary outcome will be the score on the Japanese version of the Saving Inventory-Revised. Secondary outcomes will be scores on the Clutter Image Rating Scale, the Japanese version of the Rosenberg Self-Esteem Scale and the Roles of Private Space Scale. The results will be examined for differences between the two groups in changes from baseline to 7 months. We will examine crude effects and adjust for gender and age using a general linear model for continuous variables and a logistic regression model for dichotomous variables. Sample size was calculated assuming a significance level of 5% (two tailed), a power of 80% and an effect size of 0.75. In total, 60 subjects (30 in each group) will be required. ETHICS AND DISSEMINATION: The study protocol has been approved by the Medical Ethical Committee of Teikyo University (No. 15-065). The findings will be disseminated widely through peer-reviewed publication and conference presentations. TRIAL REGISTRATION NUMBER: UMIN000020568. Issue date: 16 January 2016.
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Transtorno de Acumulação/terapia , Educação de Pacientes como Assunto/métodos , Adolescente , Adulto , Feminino , Transtorno de Acumulação/psicologia , Humanos , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/normas , Qualidade de Vida , Adulto JovemRESUMO
INTRODUCTION: Type 2 diabetes (T2D) is a significant problem, and lifestyle modifications including self-management are important. We have developed a structured individual-based lifestyle education (SILE) programme for T2D. With attention now being paid to techniques to change behaviour, we recently developed a behavioural type-specific SILE (BETSILE) programme. We aimed to evaluate the effectiveness of the BETSILE programme compared with the SILE programme for reducing glycated haemoglobin (HbA1c) in patients with T2D and special behavioural types by a cluster randomised controlled trial. METHODS AND ANALYSIS: This is a 6-month cluster randomised controlled trial with two intervention arms (BETSILE vs SILE) provided in a medical care setting by randomising registered dietitians for patients with T2D aged 20-79 years. Patients' behavioural types were classified into four types (BT1 to BT4) using an assessment sheet. We will perform independent trials for BT1 and BT2. The primary endpoint is a change from the baseline HbA1c value at 6 months. Differences between the SILE and BETSILE groups will be primarily analysed following the intention-to-treat principle. Crude and multivariate adjusted effects will be examined after adjusting for covariates, using a general linear mixed-effects model for continuous variables and a logistic regression mixed-effects model for dichotomous variables. Sample sizes needed were calculated assuming effect sizes of 0.42 and 0.33 for BT1 and BT2, respectively, an intraclass correlation of 0.02, a significance level of 5% (two-sided), a power of 80%, and equal allocation of clusters to the two arms, with each cluster having three BT1 patients for the SILE and BETSILE arms and six BT2 patients for the SILE and BETSILE arms. We will need 16 dietitians for each arm, and a total 288 patients will be required. ETHICS AND DISSEMINATION: This study has been approved by the Medical Ethical Committee of Teikyo University (No.15-222). Findings will be disseminated widely through peer-reviewed publications, etc. TRIAL REGISTRATION NUMBER: UMIN 000023087; Pre-results.
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Diabetes Mellitus Tipo 2/terapia , Comportamentos Relacionados com a Saúde , Estilo de Vida , Adulto , Idoso , Feminino , Hemoglobinas Glicadas/análise , Humanos , Japão , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Autocuidado/métodos , Adulto JovemRESUMO
In this study, we aimed to assess the effectiveness of a school-based home-collaborative lifestyle education program for adolescents (PADOK) in reducing poor subjective psychosomatic symptoms (SPS). The study was designed as a two-armed parallel cluster randomised controlled trial and the study population comprised adolescent students (aged 12-14 years, n = 1,565) who were recruited from 19 middle schools in Japan. The PADOK intervention or usual school programme was provided in schools to all eligible participants. The primary outcome was the SPS score at 6 months, while secondary outcomes included lifestyle factors, BMI, and dietary intakes. Analyses were undertaken on an intention to treat (ITT) basis accounting for the clustered design. Nineteen schools were randomised to the PADOK group (10 schools) and control group (9 schools). The numbers of students used for analysis were 1,509 for ITT and 1,420 (94.1%) for PPS. At 6 months, the crude mean change from baseline of the SPS scores by ITT analysis showed a significantly greater reduction in the PADOK group compared to that in the control group (-0.95, 95% CI -1.70 to -0.20, P = 0.016), while those for baseline-adjusted and multivariate-adjusted values showed similar directionality but were not significant (P = 0.063 and P = 0.130). The results indicated that the PADOK program may improve poor SPS scores among adolescents.
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Estilo de Vida , Transtornos Psicofisiológicos/prevenção & controle , Adolescente , Índice de Massa Corporal , Dieta , Feminino , Humanos , Japão , Masculino , Razão de Chances , Avaliação de Programas e Projetos de Saúde , Instituições Acadêmicas , TraduçãoRESUMO
INTRODUCTION: The aim of this study was to investigate the diagnostic performance of measuring antibodies to the glycopeptidolipid (GPL) core antigen specific to Mycobacterium avium complex (MAC) in patients with rheumatoid arthritis (RA). METHODS: We cross-sectionally investigated anti-GPL antibodies and radiographs of 396 patients with RA. A diagnosis of MAC pulmonary disease (MAC-PD) was made according to the criteria by the American Thoracic Society and the Infectious Diseases Society of America. Serum immunoglobulin A antibodies to MAC-specific GPL core antigen were measured by an enzyme immunoassay. All patients with RA with abnormal shadows on chest x-rays underwent chest computed tomography (CT). Bronchoscopy was performed on patients with negative cultures for MAC by expectorated sputum and positive CT findings compatible with MAC-PD. RESULTS: Ten patients were newly diagnosed with MAC-PD. Eight individuals who already had diagnoses of MAC-PD at the time of enrollment and nineteen who had negative expectorated sputum cultures for MAC and positive CT images compatible with MAC-PD and who refused bronchoscopy were excluded from the following analysis. Anti-GPL antibodies were detected in 12 of 369 patients. Eight of the ten patients with MAC-PD and 4 of 359 patients without MAC-PD tested positive for the anti-GPL antibodies. The specificity and sensitivity were 99 % and 80 %, respectively. Positive and negative predictive values were 67 %, and 97 %, respectively. When we analyzed diagnostic performance of the antibodies in 57 patients with RA who had abnormal shadows on chest x-rays, the positive and negative predictive values were 100 %, and 96 %, respectively. Twelve patients underwent bronchoscopy. Bronchoalveolar lavage fluid (BALF) samples from six patients were positive for MAC, and BALF samples from the remainder were negative. Anti-GPL antibodies were detected in the sera of all six patients with positive results for MAC by BALF sampling, whereas the antibodies were not detected in the sera from the remainder with negative results for MAC by BALF sampling. CONCLUSIONS: The measurement of anti-GPL antibodies is useful as a supplementary diagnostic tool for MAC-PD in patients with RA and may provide a new strategy, in combination with chest x-ray and CT, for differentiating MAC-PD from other pulmonary comorbidities in patients with RA.
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Anticorpos Antibacterianos/imunologia , Artrite Reumatoide/imunologia , Glicolipídeos/imunologia , Complexo Mycobacterium avium/imunologia , Infecção por Mycobacterium avium-intracellulare/imunologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Artrite Reumatoide/microbiologia , Líquido da Lavagem Broncoalveolar/microbiologia , Broncoscopia , Estudos Transversais , Feminino , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Masculino , Pessoa de Meia-Idade , Complexo Mycobacterium avium/fisiologia , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Sensibilidade e Especificidade , Escarro/microbiologia , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologiaRESUMO
It is expected that the production of the cytoprotective heme oxygenase-1 (HO-1) protein in endothelial cells would reduce severity of vascular injuries, while phenolic compounds are known to induce HO-1 mRNA and protein in various cells. We investigated the activation of HO-1 by whisky, which contains various phenolic substances. The congeners of whisky stored from 4 to 18 y in oak barrels were shown to induce an increase of HO-1 protein in human umbilical vein endothelial cells, while those of freshly distilled whisky spirit exhibited no activity. To determine the compounds with potent HO-1-inducing activity among the whisky congeners, several chemicals that had been reported to exist in whisky or oak barrels were screened, and coniferyl aldehyde and sinapyl aldehyde showed the activity. Thus, compounds that emerged in whisky during barrel storage induced cytoprotective protein, HO-1, in human endothelial cells.