[What we did and learnt in the care of the patients with dementia after the Great East Japan Earthquake in 2011].

Northeast Japan experienced an earthquake of magnitude 9.0, followed by enormous tsunamis on March 11th 2011. "The Great East Japan Earthquake" greatly affected health conditions of elderly people. Our group has reported that cognitive functions of elders were negatively influenced by this disaster. Several reasons of the cognitive deterioration could be considered such as (1) changes in the living circumstance, (2) loss of families, relatives, and friends, (3) loss of their daily activities such as farming and fishing, and (4) isolation from families and neighbors. We are now performing some anti-dementia programs including exercise, diet, and management for lifestyle-related disorders to prevent dementia.

Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR.

BACKGROUND: Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor (EGFR) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib, but little is known about how its efficacy and safety profile compares with that of standard chemotherapy. METHODS: We randomly assigned 230 patients with metastatic, non-small-cell lung cancer and EGFR mutations who had not previously received chemotherapy to receive gefitinib or carboplatin-paclitaxel. The primary end point was progression-free survival; secondary end points included overall survival, response rate, and toxic effects. RESULTS: In the planned interim analysis of data for the first 200 patients, progression-free survival was significantly longer in the gefitinib group than in the standard-chemotherapy group (hazard ratio for death or disease progression with gefitinib, 0.36; P<0.001), resulting in early termination of the study. The gefitinib group had a significantly longer median progression-free survival (10.8 months, vs. 5.4 months in the chemotherapy group; hazard ratio, 0.30; 95% confidence interval, 0.22 to 0.41; P<0.001), as well as a higher response rate (73.7% vs. 30.7%, P<0.001). The median overall survival was 30.5 months in the gefitinib group and 23.6 months in the chemotherapy group (P=0.31). The most common adverse events in the gefitinib group were rash (71.1%) and elevated aminotransferase levels (55.3%), and in the chemotherapy group, neutropenia (77.0%), anemia (64.6%), appetite loss (56.6%), and sensory neuropathy (54.9%). One patient receiving gefitinib died from interstitial lung disease. CONCLUSIONS: First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival, with acceptable toxicity, as compared with standard chemotherapy. (UMIN-CTR number, C000000376.)

Impact of the Tohoku earthquake and tsunami on pneumonia hospitalisations and mortality among adults in northern Miyagi, Japan: a multicentre observational study.

BACKGROUND: On 11 March 2011, the Tohoku earthquake and tsunami struck off the coast of northeastern Japan. Within 3 weeks, an increased number of pneumonia admissions and deaths occurred in local hospitals. METHODS: A multicentre survey was conducted at three hospitals in Kesennuma City (population 74 000), northern Miyagi Prefecture. All adults aged ≥18 years hospitalised between March 2010 and June 2011 with community-acquired pneumonia were identified using hospital databases and medical records. Segmented regression analyses were used to quantify changes in the incidence of pneumonia. RESULTS: A total of 550 pneumonia hospitalisations were identified, including 325 during the pre-disaster period and 225 cases during the post-disaster period. The majority (90%) of the post-disaster pneumonia patients were aged ≥65 years, and only eight cases (3.6%) were associated with near-drowning in the tsunami waters. The clinical pattern and causative pathogens were almost identical among the pre-disaster and post-disaster pneumonia patients. A marked increase in the incidence of pneumonia was observed during the 3-month period following the disaster; the weekly incidence rates of pneumonia hospitalisations and pneumonia-associated deaths increased by 5.7 times (95% CI 3.9 to 8.4) and 8.9 times (95% CI 4.4 to 17.8), respectively. The increases were largest among residents in nursing homes followed by those in evacuation shelters. CONCLUSIONS: A substantial increase in the pneumonia burden was observed among adults after the Tohoku earthquake and tsunami. Although the exact cause remains unresolved, multiple factors including population aging and stressful living conditions likely contributed to this pneumonia outbreak.

[Emergency medicine after a catastrophic disaster: from a view of geriatrics and gerontology].

The megathrust earthquake and the towering tsunami hit the east coast of Japan on March 11th of 2011 after intervals of 1,142 years. About 90 % of nearly 20,000 victims were drowned in devastating waves, while every town and city along the coast turned out to be a ruin. Over 400,000 people were forced to move to the evacuation centers where the evacuees slept on the floor without electricity, running water or heating systems at freezing nights. Emergency medicine, therefore, was more required during the evacuation phase than during the acute phase of the tsunami disaster. Here discussed is the phenomenon that the events happened mostly to the elderly evacuees especially in the swept area by silty polluted seawater.

Quality of life with gefitinib in patients with EGFR-mutated non-small cell lung cancer: quality of life analysis of North East Japan Study Group 002 Trial.

BACKGROUND: For non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, first-line gefitinib produced a longer progression-free survival interval than first-line carboplatin plus paclitaxel but did not show any survival advantage in the North East Japan 002 study. This report describes the quality of life (QoL) analysis of that study. METHODS: Chemotherapy-naïve patients with sensitive EGFR-mutated, advanced NSCLC were randomized to receive gefitinib or chemotherapy (carboplatin and paclitaxel). Patient QoL was assessed weekly using the Care Notebook, and the primary endpoint of the QoL analysis was time to deterioration from baseline on each of the physical, mental, and life well-being QoL scales. Kaplan-Meier probability curves and log-rank tests were employed to clarify differences. RESULTS: QoL data from 148 patients (72 in the gefitinib arm and 76 in the carboplatin plus paclitaxel arm) were analyzed. Time to defined deterioration in physical and life well-being significantly favored gefitinib over chemotherapy (hazard ratio [HR] of time to deterioration, 0.34; 95% confidence interval [CI], 0.23-0.50; p < .0001 and HR, 0.43; 95% CI, 0.28-0.65; p < .0001, respectively). CONCLUSION: QoL was maintained much longer in patients treated with gefitinib than in patients treated with standard chemotherapy, indicating that gefitinib should be considered as the standard first-line therapy for advanced EGFR-mutated NSCLC in spite of no survival advantage.

Frequency of and variables associated with the EGFR mutation and its subtypes.

Mutation in the epidermal growth factor receptor (EGFR) is frequently seen in non-small cell lung cancers (NSCLCs), especially in Asian females with adenocarcinoma. The frequency of mutation and the factors associated requires to be elucidated by analyzing a large number of consecutive clinical samples. We summarized the result of the EGFR mutation analysis for 1,176 patients performed at the time of diagnosis or relapse. The PNA-LNA PCR clamp, a highly sensitive detection method for the EGFR mutation, was employed. For fresh cases a portion of samples isolated to establish the diagnosis of lung cancer was used. For cases with a relapsed disease archival tissue were tested. The variables associated with the EGFR mutation after removing the confound factors were investigated by the logistic analysis using the samples collected in our university (n = 308) where detailed information on patients were available. The frequency of the EGFR mutation and its subtypes were investigated using all samples (n = 1,176). The EGFR mutation was significantly associated with adenocarcinoma (p = 0.006) and light-smoking (p < 0.0001), but not gender. The deletions in exon 19 were more frequently associated with male gender while exon 21 deletions were with female gender (p = 0.0011). The overall frequency of the EGFR mutation was 31%. Our result suggests that the female predominance in the EGFR mutation rate is a reflection of a higher frequency of adenocarcinoma in females. The gender difference in the mutation subtypes may provide a clue for the mechanism of the occurrence of the EGFR mutation.

Development of geriatric syndromes after taking countermeasures for polypharmacy: an overlooked issue of quitting semiregular single-dose medicine.

We report a case of an elderly woman on polypharmacy who developed appetite loss, general fatigue and muscle weakness mainly from secondary adrenal insufficiency caused by quitting one semiregular single-dose medicine. Because the degree of insufficiency was mild, her symptoms were eliminated after some time without additional treatment. The present case includes important lessons related to medication management in elderly patients. Additionally, the present case also warns us to be cautious while diagnosing geriatric syndromes as a part of the physiological aging process or additional disease symptoms. Drug-induced geriatric syndrome from quitting semiregular-use drugs should be investigated in future studies.

Could problem lists summarize comprehensive geriatric assessments? A nationwide cross-sectional survey on geriatricians' attitudes towards problem lists.

AIM: The use of problem lists is encouraged to overcome the inconsistency in reporting comprehensive geriatric assessment results. The present study aimed to identify the latent variables influencing the use of geriatrician problem lists. METHODS: Surveys were sent to all geriatricians registered with the Japan Geriatrics Society (n = 1439) as of November 2015, and responses (n = 204) were analyzed with univariate and exploratory factor analyses. To account for active, inactive and tentative items, the survey addressed "disease," "symptom" and "condition" separately. RESULTS: Most geriatricians (34.8%) composed problem lists for interdisciplinary information sharing. Nearly half of the respondents (46.6%) created problem lists for every patient. Information omissions were mainly due to the exclusion of information from other specialties (26% for omitted diseases and 12.3% for omitted symptoms), lack of time (25.5% for omitted diseases, 22.1% for omitted symptoms and 26.5% for omitted conditions), and lack of standardization of terminologies regarding observed diseases, symptoms and conditions (12.3% for omitted diseases, 19.6% for omitted symptoms and 16.7% for omitted conditions). An exploratory factor analysis, based on 20 predefined symptoms and conditions that are frequently omitted from problem lists, showed that considering the symptom "geriatric syndromes" and the condition "assistance needs in medication management" are crucial for improving problem list comprehensiveness. CONCLUSIONS: Geriatricians commonly use problem lists; however, there is considerable variation regarding the problems listed and their relationships. The listings of "geriatric syndrome" and "assistance needs in medication management" are crucial for improving problem list comprehensiveness. Geriatr Gerontol Int 2019; 19: 159-164.

Nitroglycerin treatment may enhance chemosensitivity to docetaxel and carboplatin in patients with lung adenocarcinoma.

PURPOSE: Nitroglycerin may improve the response to chemotherapy in advanced non-small cell lung cancer. The effects and mechanisms of nitroglycerin on the enhancement of chemosensitivity to docetaxel and carboplatin regimen (DCb) in patients with lung adenocarcinoma have not been reported. EXPERIMENTAL DESIGN: Seventeen patients with operable lung adenocarcinoma and stable angina pectoris were selected to investigate the effects of nitroglycerin on immunoreactivity for hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), P-glycoprotein (P-gp), the production of which is regulated by HIF-1, and p53 proteins in their resected tumor by semiquantitative immunohistochemical analyses. Eight of 17 patients were treated with nitroglycerin patches before operation, but 9 of 17 patients were not. Furthermore, to study the relationship between changes in plasma VEGF levels by nitroglycerin treatment and response to DCb, 29 patients with advanced lung adenocarcinoma were treated with nitroglycerin for 3 days before chemotherapy using DCb. RESULTS: The rates of immunoreactive cells for HIF-1alpha, VEGF, and P-gp in tumor tissues treated with nitroglycerin were lower than those without nitroglycerin, but those for p53 were not different between those treated with and without nitroglycerin. Furthermore, the rates of immunoreactive cells for VEGF and P-gp proteins were significantly associated with those for HIF-1alpha in tumor tissue. The magnitude of decrease in plasma VEGF levels after treatment with nitroglycerin was significantly associated with response to DCb in patients with advanced lung adenocarcinoma. CONCLUSIONS: Nitroglycerin treatment may improve response to DCb in patients with lung adenocarcinoma, partly through decreasing VEGF and P-gp production via reduction of HIF-1alpha.

Introduction and overview of the special issue "Brain imaging and aging": The new era of neuroimaging in aging research.

It is well known that the brain is one of the organs particularly affected by aging in terms of function, relative to the gastrointestinal tract and liver, which exhibit less functional decline. There is also a wide range of age-related neurological disorders such as stroke, Alzheimer's disease, and Parkinson's disease. Therefore, it is very important to understand the relationship between functional age-related change and neurological dysfunction. Neuroimaging techniques including magnetic resonance imaging and positron emission tomography have been significantly improved over recent years. Many physicians and researchers have investigated various mechanisms of age-related cerebral change and associated neurological disorders using neuroimaging techniques. In this special issue of Ageing Research Reviews, we focus on cerebral- and neuro-imaging, which are a range of tools used to visualize structure, functions, and pathogenic molecules in the nervous system. In addition, we summarize several review articles about the history, present values, and future perspectives of neuroimaging modalities.

Changes in Cognitive Functions in the Elderly Living in Temporary Housing after the Great East Japan Earthquake.

On March 11, 2011, Japan experienced an earthquake of magnitude 9.0 and subsequent enormous tsunamis. This disaster destroyed many coastal cities and caused nearly 20,000 casualties. In the aftermath of the disaster, many tsunami survivors who lost their homes were forced to live in small temporary apartments. Although all tsunami survivors were at risk of deteriorating health, the elderly people were particularly at a great risk with regard to not only their physical health but also their mental health. In the present study, we performed a longitudinal cohort study to investigate and analyze health conditions and cognitive functions at 28, 32, and 42 months after the disaster in the elderly people who were forced to reside in temporary apartments in Kesennuma, a city severely damaged by the tsunamis. The ratio of people considered to be cognitively impaired significantly increased during the research period. On the other hand, the mean scores of the Kessler Psychological Distress Scale-6 and Athens Insomnia Scale improved based on the comparison between the data at 24 and 42 months. The multiple logistic regression analysis revealed that frequency of "out-of-home activities" and "walking duration" were independently associated with an increase in the ratio of people with cognitive impairment. We concluded that the elderly people living in temporary apartments were at a high risk of cognitive impairment and "out-of-home activities" and "walking" could possibly maintain the stability of cognitive functions.

First-line gefitinib for elderly patients with advanced NSCLC harboring EGFR mutations. A combined analysis of North-East Japan Study Group studies.

OBJECTIVE: To assess outcomes of elderly patients with advanced NSCLC harboring an EGFR mutation treated with gefitinib, as well as safety and impact on quality of life (QoL). METHODS: We performed a retrospective analysis of pooled data from one Phase III and two Phase II studies of 71 patients aged ≥ 70 years with a performance status of 0 - 2. The main outcome measures were progression-free survival (PFS), overall survival (OS) and response rate (RR), as well as incidence of adverse events and time to 9.1% deterioration in QoL. RESULTS: Median PFS (14.3 vs 5.7 months, p < 0.001) and overall RR (73.2 vs 26.5%, p < 0.001) in the gefitinib group were superior to those in the standard chemotherapy group, whereas median OS was not significantly different (30.8 vs 26.4 months, p = 0.42). Elevation of aspartate transaminase and/or alanine transaminase (18.3%) was the most common adverse event, and one treatment-related death (pneumonitis) occurred. Time to 9.1% deterioration in the QoL domains of pain and dyspnea, anxiety, and daily functioning was similar between the two age groups. CONCLUSION: First-line gefitinib is efficacious with acceptable toxicity in relatively fit elderly patients with advanced NSCLC harboring an EGFR mutation.

Expression of nitric oxide synthase-2 in the lungs decreases airway resistance and responsiveness.

Individuals with asthma have increased levels of nitric oxide in their exhaled air. To explore its role, we have developed a regulatable transgenic mouse capable of overexpressing inducible nitric oxide synthase in a lung-specific fashion. The CC10-rtTA-NOS-2 mouse contains two transgenes, a reverse tetracycline transactivator under the control of the Clara cell protein promoter and the mouse nitric oxide synthase-2 (NOS-2) coding region under control of a tetracycline operator. Addition of doxycycline to the drinking water of CC10-rtTA-NOS-2 mice causes an increase in nitric oxide synthase-2 that is largely confined to the airway epithelium. The fraction of expired nitric oxide increases over the first 24 h from approximately 10 parts per billion to a plateau of approximately 20 parts per billion. There were no obvious differences between CC10-rtTA-NOS-2 mice, with or without doxycycline, and wild-type mice in lung histology, bronchoalveolar protein, total cell count, or count differentials. However, airway resistance was lower in CC10-rtTA-NOS-2 mice with doxycycline than in CC10-rtTA-NOS-2 mice without doxycycline or wild-type mice with doxycycline. Moreover, doxycycline-treated CC10-rtTA-NOS-2 mice were hyporesponsive to methacholine compared with other groups. These data suggest that increased nitric oxide in the airways has no proinflammatory effects per se and may have beneficial effects on pulmonary function.

First-line gefitinib in patients aged 75 or older with advanced non-small cell lung cancer harboring epidermal growth factor receptor mutations: NEJ 003 study.

INTRODUCTION: Recent studies have demonstrated that first-line treatment with gefitinib, an epidermal growth factor receptor (EFGR)-targeted tyrosine kinase inhibitor, is significantly superior to standard chemotherapy for advanced non-small-cell lung cancer (NSCLC) harboring EGFR sensitive mutations. Meanwhile, the efficacy of gefitinib therapy among elderly populations diagnosed with EGFR-mutated NSCLC has not yet been elucidated. The purpose of this study was to investigate the efficacy and feasibility of gefitinib for chemotherapy-naive patients aged 75 or older with NSCLC harboring EGFR mutations; generally, these patients have no indication for treatment with platinum doublets. METHODS: Chemotherapy-naive patients aged 75 years or older with performance status 0 to 1 and advanced NSCLC harboring EGFR mutations, as determined by the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method, were enrolled. The enrolled patients received 250 mg/day of gefitinib orally. RESULTS: Between January 2008 and May 2009, 31 patients were enrolled, all of whom were eligible. The median age was 80 (range, 75-87) years. Twenty-five patients (81%) were women, and 30 patients (97%) had adenocarcinoma. The overall response rate was 74% (95% confidence interval, 58%-91%), and the disease control rate was 90%. The median progression-free survival was 12.3 months. The common adverse events were rash, diarrhea, and liver dysfunction. One treatment-related death because of interstitial lung disease occurred. CONCLUSIONS: This is the first study that verified safety and efficacy of first-line treatment with gefitinib in elderly patients having advanced NSCLC with EGFR mutation. Considering its strong antitumor activity and mild toxicity, first-line gefitinib may be preferable to standard chemotherapy for this population.

First-line gefitinib for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy.

PURPOSE: This multicenter phase II study was undertaken to investigate the efficacy and feasibility of gefitinib for patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations without indication for chemotherapy as a result of poor performance status (PS). PATIENTS AND METHODS: Chemotherapy-naïve patients with poor PS (patients 20 to 74 years of age with Eastern Cooperative Oncology Group PS 3 to 4, 75 to 79 years of age with PS 2 to 4, and >or= 80 years of age with PS 1 to 4) who had EGFR mutations examined by the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method were enrolled and received gefitinib (250 mg/d) alone. RESULTS: Between February 2006 and May 2007, 30 patients with NSCLC and poor PS, including 22 patients with PS 3 to 4, were enrolled. The overall response rate was 66% (90% CI, 51% to 80%), and the disease control rate was 90%. PS improvement rate was 79% (P < .00005); in particular, 68% of the 22 patients improved from >or= PS 3 at baseline to