Association between socioeconomic status and prolonged television viewing time in a general Japanese population: NIPPON DATA2010.

BACKGROUND: It has been pointed out that prolonged television (TV) viewing is one of the sedentary behaviors that is harmful to health; however, the association between socioeconomic status (SES) and prolonged TV viewing time has not been sufficiently investigated in Japan. METHODS: The study population are the participants of NIPPON DATA2010, which is a prospective cohort study of the National Health and Nutrition Survey 2010 in Japan. They were residents in 300 randomly selected areas across Japan. This study included 2752 adults. SES was classified according to the employment status, educational attainment, living status, and equivalent household expenditure (EHE). Prolonged TV viewing time was defined as more than or equal to 4 h of TV viewing per day. Multivariable logistic regression analyses were conducted to examine the association of SES with prolonged TV viewing time. RESULTS: The mean TV viewing time was 2.92 h in all participants. Of 2752 participants, 809 (29.4%) prolonged TV viewing, and the mean TV viewing time of them was 5.61 h. The mean TV viewing time in participants without prolonged TV viewing time was 1.81 h. The mean TV viewing time was prolonged as age classes increased and significantly longer in aged ≥60 years. Prolonged TV viewing time was associated with not working for all age classes and sexes. Only among women, education attainment and living status were also associated with prolonged TV viewing time. For education attainment, the lower the received years of education, the higher odds ratios (OR) of prolonged TV viewing time. For living status, in women aged <60 years, living with others had a significantly higher OR compared to living with spouse. On the other hand, in women aged ≥60 years, living alone had a significantly higher OR. EHE did not have any significant associations with prolonged TV viewing time. CONCLUSIONS: In a general Japanese population, it should be noted that the association between SES and prolonged TV viewing time differed by age and sex. Particularly, it must draw attention to the prolonged TV viewing in elderly. The intervention in order to shorten TV viewing time needs to consider these attributes.

Exercise Habits Are Associated with Improved Long-Term Mortality Risks in the Nationwide General Japanese Population: A 20-Year Follow-Up of the NIPPON DATA90 Study.

Exercise habits are known as a protective factor for a variety of diseases and thus recommended worldwide; however, few studies have examined long-term effects of exercise habits on mortality. We continuously monitored death status in a nationwide population sample of 7,709 eligible persons from the National Integrated Project for Prospective Observation of Noncommunicable Disease and its Trends in the Aged in 1990 (NIPPON DATA90), for which baseline data were obtained in 1990. To investigate the long-term impact of baseline exercise habits, we calculated the relative risk of non-exercisers (participants without regular voluntary exercise habits) in reference to exercisers (those with these habits) for all-cause or cause-specific mortality using a Cox proportional hazard model, in which the following confounding factors were appropriately adjusted: sex, age, body mass index, total energy intake, smoking, drinking, and history of cardiovascular disease. During a median 20 years of follow-up, 1,747 participants died, 99 of heart failure. The risk for all-cause mortality was 12% higher in non-exercisers than in exercisers (95% confidence interval, 1%-24%), which was also observed for mortality from heart failure, as 68% higher in non-exercisers than in exercises (95% confidence interval, 3%-173%). These associations were similarly observed when the participants were divided to subgroups by sex, age, and the light, moderate, or vigorous intensity of physical activity, without any significant heterogeneities (P > 0.1). The present study has revealed significant impact of exercise habits on long-term mortality risks, supporting worldwide recommendations for improvement of exercise habits.

Socioeconomic and lifestyle factors associated with depressive tendencies in general Japanese men and women: NIPPON DATA2010.

BACKGROUND: The gender-specific characteristics of individuals at an increased risk of developing depression currently remain unclear despite a higher prevalence of depression in women than in men. This study clarified socioeconomic and lifestyle factors associated with an increased risk of subclinical depression in general Japanese men and women. METHODS: Study participants were residents not receiving psychiatric treatments in 300 sites throughout Japan in 2010 (1152 men, 1529 women). Multivariable-adjusted odds ratios (OR) and 95% confidence intervals (95%CIs) for socioeconomic factors and lifestyle factors were calculated using a logistic regression analysis. RESULTS: Risk of depressive tendencies was significantly higher in men who were single and living alone (OR, 3.27; 95% CI, 1.56-6.88) than those married. The risk was significantly lower in women who were not working and aged ≥ 60 years (OR, 0.39; 95% CI, 0.22-0.68) and higher in men who were not working and aged < 60 years (OR, 3.57; 95%CI, 1.31-9.72) compared with those who were working. Current smoking was also associated with a significantly increased risk of depressive tendencies in women (OR, 2.96; 95% CI, 1.68-5.22) but not in men. CONCLUSIONS: Socioeconomic and lifestyle factors were associated with an increased risk of depressive tendencies in general Japanese. Related factors were different by sex.

A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response.

Targeted therapies have demonstrated efficacy against specific subsets of molecularly defined cancers. Although most patients with lung cancer are stratified according to a single oncogenic driver, cancers harbouring identical activating genetic mutations show large variations in their responses to the same targeted therapy. The biology underlying this heterogeneity is not well understood, and the impact of co-existing genetic mutations, especially the loss of tumour suppressors, has not been fully explored. Here we use genetically engineered mouse models to conduct a 'co-clinical' trial that mirrors an ongoing human clinical trial in patients with KRAS-mutant lung cancers. This trial aims to determine if the MEK inhibitor selumetinib (AZD6244) increases the efficacy of docetaxel, a standard of care chemotherapy. Our studies demonstrate that concomitant loss of either p53 (also known as Tp53) or Lkb1 (also known as Stk11), two clinically relevant tumour suppressors, markedly impaired the response of Kras-mutant cancers to docetaxel monotherapy. We observed that the addition of selumetinib provided substantial benefit for mice with lung cancer caused by Kras and Kras and p53 mutations, but mice with Kras and Lkb1 mutations had primary resistance to this combination therapy. Pharmacodynamic studies, including positron-emission tomography (PET) and computed tomography (CT), identified biological markers in mice and patients that provide a rationale for the differential efficacy of these therapies in the different genotypes. These co-clinical results identify predictive genetic biomarkers that should be validated by interrogating samples from patients enrolled on the concurrent clinical trial. These studies also highlight the rationale for synchronous co-clinical trials, not only to anticipate the results of ongoing human clinical trials, but also to generate clinically relevant hypotheses that can inform the analysis and design of human studies.

Relationship Between Socioeconomic Status and the Prevalence of Underweight, Overweight or Obesity in a General Japanese Population: NIPPON DATA2010.

BACKGROUND: Socioeconomic status (SES) imbalances in developed and developing countries may result in individuals being overweight and obese. However, few studies have investigated this issue in Japan. We herein examined the relationship between SES and being underweight, overweight or obese according to sex and age groups (20-64 or ≥65 years) in Japan. METHODS: In 2010, we established a cohort of participants in the National Health and Nutrition Survey of Japan. We divided 2,491 participants (1,081 men and 1,410 women) according to the WHO definitions of underweight, overweight or obesity and performed multinomial logistic analyses using BMI <18.5 kg/m2 (underweight), BMI 25.0-29.9 kg/m2 (overweight), and BMI ≥30.0 kg/m2 (obese) versus BMI 18.5-24.9 kg/m2 (normal) as the outcome, with SES groups as the main explanatory variables. RESULTS: In adult men, a lower education level relative to a higher education level was inversely associated with obesity after adjustments for other SESs (odds ratio [OR] 0.41; 95% confidence interval [CI], 0.18-0.96). However, in adult women, lower education level was positively associated with being overweight and obese (OR 1.67; 95% CI, 1.07-2.49 for overweight and OR 2.66; 95% CI, 1.01-7.01 for obese). In adult women, a lower household income was positively associated with being overweight and obese (obese: OR 4.84; 95% CI, 1.36-17.18 for those with a household income <2 million JPY relative to those with ≥6 million JPY). CONCLUSIONS: In adult women, a lower education level and lower household income were positively associated with being overweight or obese. In contrast, in adult men, a lower education level was inversely associated with obesity. Gender and age differences in SESs affect the prevalence of being overweight or obese.

Safety and pharmacokinetics of imaradenant (AZD4635) in Japanese patients with advanced solid malignancies: a phase I, open-label study.

PURPOSE: Imaradenant is a novel potent and selective adenosine A2A receptor antagonist that is hypothesized to reduce immune suppression in the tumor microenvironment. This phase I, open-label, dose-escalation study evaluated the safety, pharmacokinetics, and anti-tumor activity of imaradenant. METHODS: Japanese patients with advanced solid malignancies received imaradenant 50 mg (n = 3) or 75 mg (n = 7) once daily (QD). The primary objective was safety and tolerability, and the secondary objectives were pharmacokinetics and anti-tumor activity. RESULTS: The median treatment duration was 2.10 months and 2.14 months for the 50- and 75-mg QD cohorts, respectively. The most common adverse events were nausea, malaise, decreased appetite, and vomiting. Five patients (50%) reported adverse events that were considered causally related to imaradenant; three patients had Grade 2 adverse events of malaise, nausea, and diarrhea. No deaths or serious adverse events occurred. The median times of maximum observed concentrations sampled after a single dose in the 50- and 75-mg QD cohorts were 1.08 h (range, 0.95-1.95) and 2.00 h (range, 0.92-5.52), respectively. There was little accumulation after multiple dosing, with geometric mean accumulation ratios of maximum concentration of 1.3 (50-mg QD) to 1.4 (75-mg QD) and area under the concentration-time curve 0-24 of 1.4 (50-mg QD) to 1.5 (75-mg QD). The best objective response was stable disease (3/10). CONCLUSION: No new or unexpected safety concerns were identified, and imaradenant had an acceptable safety profile at both 50- and 75-mg QD. CLINICALTRIALS: gov identifier NCT03980821 (June 10, 2019).

[Treatment indications for sarcopenia: a systematic review of exercise intervention effect].

OBJECTIVE: To evaluate exercise intervention efficacy for the prevention and treatment of sarcopenia in the elderly. METHODS: We conducted a systematic literature search of randomized controlled trials in the Physical Activity Guidelines Advisory Committee Report (before 2007), Pubmed, the Cochrane database, and Igaku Chuo Zasshi (January 2006 to August 2009). DATA EXTRACTION: Two authors independently extracted relevant data. A total of 951 articles were found by search engines, and 9 studies were finally selected after a review by 2 experts. The content of these studies, especially duration, sets, periods, frequency, and intensity of exercise intervention were extracted and summarized in a results table. Five of 6 articles concluded that high-intensity resistance training significantly increased soft lean tissue and muscle mass. The remaining 3 articles indicated that moderate-intensity resistance training did not affect soft lean tissue or muscle mass. CONCLUSION: This systematic review suggested that high-intensity resistance training with sufficient periods, frequency, repetitions, and sets is effective to counteract the loss of muscle mass associated with advancing age.

Association between socioeconomic status and physical inactivity in a general Japanese population: NIPPON DATA2010.

BACKGROUND: Lower socioeconomic status (SES) may be related to inactivity lifestyle; however, the association between SES and physical inactivity has not been sufficiently investigated in Japan. METHODS: The study population is the participants of NIPPON DATA2010, which is a prospective cohort study of the National Health and Nutrition Survey 2010 in Japan. They were residents in 300 randomly selected areas across Japan. This study included 2,609 adults. Physical activity was assessed by physical activity index (PAI) calculated from activity intensity and time. The lowest tertile of PAI for each 10-year age class and sex was defined as physical inactivity. Multivariable logistic regression analyses were conducted to examine the association of SES (employment status, educational attainment, living status, and equivalent household expenditure (EHE)) with physical inactivity. RESULTS: In the distribution of PAI by age classes and sex, the highest median PAI was aged 30-39 years among men (median 38.6), aged 40-49 years among women (38.0), and median PAI was decreased with increasing age. Multivariable-adjusted model shows that not working was significantly associated with physical inactivity after adjustment for age in all age groups and sexes. Not living with spouse for adult women and elderly men was significantly associated with physical inactivity compared to those who living with spouse. However, neither educational attainment nor EHE had any significant associations with physical inactivity. CONCLUSIONS: The result indicated that physical inactivity was associated with SES in a general Japanese population. SES of individuals need to be considered in order to prevent inactivity lifestyle.

Oncogenic switch and single-agent MET inhibitor sensitivity in a subset of EGFR-mutant lung cancer.

The clinical efficacy of epidermal growth factor receptor (EGFR)­targeted therapy in EGFR-mutant non­small cell lung cancer is limited by the development of drug resistance. One mechanism of EGFR inhibitor resistance occurs through amplification of the human growth factor receptor (MET) proto-oncogene, which bypasses EGFR to reactivate downstream signaling. Tumors exhibiting concurrent EGFR mutation and MET amplification are historically thought to be codependent on the activation of both oncogenes. Hence, patients whose tumors harbor both alterations are commonly treated with a combination of EGFR and MET tyrosine kinase inhibitors (TKIs). Here, we identify and characterize six patient-derived models of EGFR-mutant, MET-amplified lung cancer that have switched oncogene dependence to rely exclusively on MET activation for survival. We demonstrate in this MET-driven subset of EGFR TKI-refractory cancers that canonical EGFR downstream signaling was governed by MET, even in the presence of sustained mutant EGFR expression and activation. In these models, combined EGFR and MET inhibition did not result in greater efficacy in vitro or in vivo compared to single-agent MET inhibition. We further identified a reduced EGFR:MET mRNA expression stoichiometry as associated with MET oncogene dependence and single-agent MET TKI sensitivity. Tumors from 10 of 11 EGFR inhibitor­resistant EGFR-mutant, MET-amplified patients also exhibited a reduced EGFR:MET mRNA ratio. Our findings reveal that a subset of EGFR-mutant, MET-amplified lung cancers develop dependence on MET activation alone, suggesting that such patients could be treated with a single-agent MET TKI rather than the current standard-of-care EGFR and MET inhibitor combination regimens.

One-year weight loss maintenance outcomes following a worksite-based weight reduction program among Japanese men with cardiovascular risk factors.

OBJECTIVES: Worksite-based programs present a simple and effective approach to facilitate weight reduction in employees. Despite the importance of 1-year weight loss maintenance, studies have generally focused on the short-term effects of weight reduction programs. In addition, little is known about the long-term weight maintenance outcomes in Asian populations. We examined the long-term maintenance effects of a worksite-based weight reduction program among Japanese men with cardiovascular risk factors. METHODS: The study sample comprised 58 overweight men with cardiovascular risk factors who had voluntarily participated in a randomized crossover trial involving a 3-month weight reduction program. Participants were followed up for 1 year after the trial concluded, and both groups were merged for the analysis. We compared the changes in body weight before the post-trial follow-up and after 12 months to examine the long-term maintenance effects of the program. Changes in other cardiovascular risk factors (eg, waist circumference, blood pressure, lipid measures, and diabetes-related measures) were also examined. RESULTS: Both groups of study participants achieved weight loss during the weight reduction program. Total 53 participants (91.4%) completed the 12-month post-trial follow-up. There were no significant changes in mean body weight (mean: -0.11, 95% confidence interval: -0.7-0.49 kg) and other cardiovascular risk factors between the beginning and end of the follow-up period. CONCLUSIONS: This study showed that the worksite-based weight reduction program not only enabled short-term weight loss, but that the participants were able to successfully maintain their weight for 1 year after the program without any supplementary interventions.