Deep learning-assisted (automatic) diagnosis of glaucoma using a smartphone.

BACKGROUND/AIMS: To validate a deep learning algorithm to diagnose glaucoma from fundus photography obtained with a smartphone. METHODS: A training dataset consisting of 1364 colour fundus photographs with glaucomatous indications and 1768 colour fundus photographs without glaucomatous features was obtained using an ordinary fundus camera. The testing dataset consisted of 73 eyes of 73 patients with glaucoma and 89 eyes of 89 normative subjects. In the testing dataset, fundus photographs were acquired using an ordinary fundus camera and a smartphone. A deep learning algorithm was developed to diagnose glaucoma using a training dataset. The trained neural network was evaluated by prediction result of the diagnostic of glaucoma or normal over the test datasets, using images from both an ordinary fundus camera and a smartphone. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AROC). RESULTS: The AROC with a fundus camera was 98.9% and 84.2% with a smartphone. When validated only in eyes with advanced glaucoma (mean deviation value < -12 dB, N=26), the AROC with a fundus camera was 99.3% and 90.0% with a smartphone. There were significant differences between these AROC values using different cameras. CONCLUSION: The usefulness of a deep learning algorithm to automatically screen for glaucoma from smartphone-based fundus photographs was validated. The algorithm had a considerable high diagnostic ability, particularly in eyes with advanced glaucoma.

Effects of Study Population, Labeling and Training on Glaucoma Detection Using Deep Learning Algorithms.

Purpose: To compare performance of independently developed deep learning algorithms for detecting glaucoma from fundus photographs and to evaluate strategies for incorporating new data into models. Methods: Two fundus photograph datasets from the Diagnostic Innovations in Glaucoma Study/African Descent and Glaucoma Evaluation Study and Matsue Red Cross Hospital were used to independently develop deep learning algorithms for detection of glaucoma at the University of California, San Diego, and the University of Tokyo. We compared three versions of the University of California, San Diego, and University of Tokyo models: original (no retraining), sequential (retraining only on new data), and combined (training on combined data). Independent datasets were used to test the algorithms. Results: The original University of California, San Diego and University of Tokyo models performed similarly (area under the receiver operating characteristic curve = 0.96 and 0.97, respectively) for detection of glaucoma in the Matsue Red Cross Hospital dataset, but not the Diagnostic Innovations in Glaucoma Study/African Descent and Glaucoma Evaluation Study data (0.79 and 0.92; P < .001), respectively. Model performance was higher when classifying moderate-to-severe compared with mild disease (area under the receiver operating characteristic curve = 0.98 and 0.91; P < .001), respectively. Models trained with the combined strategy generally had better performance across all datasets than the original strategy. Conclusions: Deep learning glaucoma detection can achieve high accuracy across diverse datasets with appropriate training strategies. Because model performance was influenced by the severity of disease, labeling, training strategies, and population characteristics, reporting accuracy stratified by relevant covariates is important for cross study comparisons. Translational Relevance: High sensitivity and specificity of deep learning algorithms for moderate-to-severe glaucoma across diverse populations suggest a role for artificial intelligence in the detection of glaucoma in primary care.

Validation of a Deep Learning Model to Screen for Glaucoma Using Images from Different Fundus Cameras and Data Augmentation.

PURPOSE: To validate a deep residual learning algorithm to diagnose glaucoma from fundus photography using different fundus cameras at different institutes. DESIGN: Cross-sectional study. PARTICIPANTS: A training dataset consisted of 1364 color fundus photographs with glaucomatous indications and 1768 color fundus photographs without glaucomatous features. Two testing datasets consisted of (1) 95 images of 95 glaucomatous eyes and 110 images of 110 normative eyes, and (2) 93 images of 93 glaucomatous eyes and 78 images of 78 normative eyes. METHODS: A deep learning algorithm known as Residual Network (ResNet) was used to diagnose glaucoma using a training dataset. The 2 testing datasets were obtained using different fundus cameras (different manufacturers) across multiple institutes. The size of the training data was artificially increased by adding minor alterations to the original data, known as "image augmentation." Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AROC). MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve. RESULTS: When image augmentation was not used, the AROC was 94.8% (90.3-96.8) in the first testing dataset and 99.7% (99.4-100.0) in the second dataset. These AROC values were significantly (P < 0.05) smaller without augmentation (87.7% [82.8-92.6] in the first testing dataset and 94.5% [91.3-97.6] in the second testing dataset). CONCLUSIONS: The previously developed deep residual learning algorithm achieved high diagnostic performance with different fundus cameras across multiple institutes, in particular when image augmentation was used.

Factors Associated with Potassium-Competitive Acid Blocker Non-Response in Patients with Proton Pump Inhibitor-Refractory Gastroesophageal Reflux Disease.

BACKGROUND/AIMS: Approximately 20-40% of patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI) treatment. The acid-inhibitory effect of vonoprazan, a novel potassium-competitive acid blocker (P-CAB), is significantly greater when compared to the effect of PPIs. We investigated the efficacy of vonoprazan treatment for PPI-refractory GERD and factors associated with P-CAB non-response. METHODS: We enrolled 277 GERD patients receiving continuous PPI therapy. Subjects completed a self-report questionnaire including the frequency scale for the symptoms of GERD (FSSG). Patients with PPI-refractory GERD received 20 mg of vonoprazan once daily for 8 weeks. After that, subjects completed the same questionnaire, and the results were used to identify P-CAB responders and non-responders. RESULTS: Twenty-eight patients were identified as P-CAB responders and 26 were non-responders. Vonoprazan treatment significantly decreased scores of FSSG, nighttime symptom, and Athens Insomnia Scale. Multivariate analysis demonstrated co-existing functional dyspepsia (FD; OR 4.94) and the presence of sleep disturbances (OR 4.34) was associated with P-CAB non-response, whereas alcohol consumption was inversely associated. CONCLUSIONS: Vonoprazan treatment might be appropriate as a promising new strategy for PPI-refractory GERD. Co-existing FD, sleep disturbances, and alcohol abstinence were significantly associated with P-CAB non-response. Other therapeutic options should be considered in patients with these factors.

Associations among gastroesophageal reflux disease, psychological stress, and sleep disturbances in Japanese adults.

BACKGROUND AND AIM: Gastroesophageal reflux disease (GERD) and psychological stress are associated with sleep disturbances. The aim of the present study was to examine the prevalence of sleep disturbances, anxiety, and depression by GERD subtypes and to identify factors associated with sleep disturbances in general population. METHODS: A total of 2002 Japanese subjects, who underwent annual health checkups, were enrolled and asked to fill out a questionnaire, including the frequency scale for the symptoms of GERD (FSSG), Athens Insomnia Scale (AIS), Rome III questionnaire, and Hospital Anxiety and Depression Scale (HADS). GERD was divided into asymptomatic erosive reflux disease (a-ERD), symptomatic ERD (s-ERD), and non-erosive reflux disease (NERD), according to the presence or absence of esophageal mucosal injury on endoscopy, and the FSSG scores. Sleep disturbances were diagnosed in subjects with AIS score ≥6. RESULTS: Prevalence of sleep disturbances was significantly higher in GERD subjects than in controls (35.9 and 14.7%, respectively), especially, in the NERD group (45.1%). Sleep duration was significantly shorter in the s-ERD group compared with other groups. Subjects in the NERD and s-ERD groups showed higher HADS scores, resulting in higher incidences of anxiety and depression than those in the control and a-ERD groups. Reflux symptoms, anxiety, depression, and coexisting functional dyspepsia, but not the presence of esophageal mucosal injury, were associated with an increased odds ratio for sleep disturbances. CONCLUSION: There were significant positive associations among reflux symptoms, psychological stress, and sleep disturbance in Japanese adults. Further studies investigating the efficacy of therapy are needed.

Additional surgical resection after endoscopic mucosal dissection for early gastric cancer: A medium-sized hospital's experience.

PURPOSE: In Japan, the majority of early gastric cancers (EGCs) are now treated with endoscopic submucosal dissection (ESD). Patients with non-curative lesions treated by ESD are advised to undergo additional surgical resection (ASR) based on guidelines from the Japan Gastroenterological Endoscopy Society (JGES) and Japanese Gastric Cancer Association (JGCA). However, many studies have demonstrated that residual cancer and lymph node metastasis are only rarely found in ASR specimens. Here we retrospectively analyzed the conditions that could enable the avoidance of unnecessary ASR. METHODS: The ESD data for 114 absolute indication lesions and 26 lesions of expanded indication lesions were analyzed. The indications and the curability were evaluated according to the JGES/JGCA guidelines. RESULTS: The rates of non-curative resection and ASR were significantly higher in the expanded indication group compared to the absolute indication group (26.9% and 19.2% vs. 7.9% and 0.9%, respectively). ASR was performed for six patients. Three of their ARS specimens contained neither residual cancer nor lymph node metastasis, and the pathological findings of the preceding ESD specimens deviated slightly from the curative criteria defined by the guidelines. The conditions of the lesions that did not meet the curative criteria were as follows: (1) sm1 invasion of undifferentiated-type lesion <10 mm dia., (2) 21-25 mm dia. mucosal undifferentiated-type lesion, or (3) peacemeal resection with a horizontal margin positive for the mucosal differentiated-type. CONCLUSIONS: These data suggest that a close follow-up without ASR might be appropriate for patients in the above-mentioned three categories after non-curative ESD for EGC.

GERD and sleep disturbances.

Gastroesophageal reflux disease(GERD) is strongly associated with sleep disturbances. Several studies have shown that gastroesophageal reflux disease is strongly associated with sleep disturbances. Proton pump inhibitor(PPI) therapy improves subjective sleep parameters in GERD patients; however, the effects of this therapy on objective sleep parameters remain controversial. Numerous factors such as stress, lifestyle, and surrounding circumstances affect sleep status in humans, it is hard to examine the direct effect of acid reflux on sleep in patients with GERD. In this paper, we show that acid reflux directly causes sleep disturbances in rats with chronic esophagitis and esomeprazole significantly improved some objective sleep parameters in Japanese GERD patients.

Rebamipide Alters the Esophageal Microbiome and Reduces the Incidence of Barrett's Esophagus in a Rat Model.

BACKGROUND: Barrett's esophagus (BE) is characterized by a distinct Th2-predominant cytokine profile. However, antigens that shift the immune response toward the Th2 profile are unknown. AIM: We examined the effects of rebamipide on the esophageal microbiome and BE development in a rat model. METHODS: BE was induced by esophagojejunostomy in 8-week-old male Wistar rats. Rats were divided into control and rebamipide-treated group receiving either a normal or a 0.225 % rebamipide-containing diet, respectively, and killed 8, 16, 24, and 32 weeks after the operation. PCR-amplified 16S rDNAs extracted from esophageal samples were examined by terminal-restriction fragment length polymorphism (T-RFLP) analysis to assess microbiome composition. The dynamics of four bacterial genera (Lactobacillus, Clostridium, Streptococcus, and Enterococcus) were analyzed by real-time PCR. RESULTS: The incidences of BE in the control and rebamipide group at 24 and 32 weeks were 80 and 100, and 20 and 33 %, respectively. T-RFLP analysis of normal esophagus revealed that the proportion of Clostridium was 8.3 %, while that of Lactobacillales was 71.8 %. The proportions of Clostridium increased and that of Lactobacillales decreased at 8 weeks in both groups. Such changes were consistently observed in the control but not in the rebamipide group. Clostridium and Lactobacillus expression was lower and higher, respectively, in the rebamipide group than in the control group. CONCLUSIONS: Rebamipide reduced BE development and altered the esophageal microbiome composition, which might play a role in BE development.

Acid reflux directly causes sleep disturbances in rat with chronic esophagitis.

BACKGROUND & AIMS: Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Proton pump inhibitor (PPI) therapy improves subjective but not objective sleep parameters in patients with GERD. This study aimed to investigate the association between GERD and sleep, and the effect of PPI on sleep by using a rat model of chronic acid reflux esophagitis. METHODS: Acid reflux esophagitis was induced by ligating the transitional region between the forestomach and the glandular portion and then wrapping the duodenum near the pylorus. Rats underwent surgery for implantation of electrodes for electroencephalogram and electromyogram recordings, and they were transferred to a soundproof recording chamber. Polygraphic recordings were scored by using 10-s epochs for wake, rapid eye movement sleep, and non-rapid eye movement (NREM) sleep. To examine the role of acid reflux, rats were subcutaneously administered a PPI, omeprazole, at a dose of 20 mg/kg once daily. RESULTS: Rats with reflux esophagitis presented with several erosions, ulcers, and mucosal thickening with basal hyperplasia and marked inflammatory infiltration. The reflux esophagitis group showed a 34.0% increase in wake (232.2±11.4 min and 173.3±7.4 min in the reflux esophagitis and control groups, respectively; p<0.01) accompanied by a reduction in NREM sleep during light period, an increase in sleep fragmentation, and more frequent stage transitions. The use of omeprazole significantly improved sleep disturbances caused by reflux esophagitis, and this effect was not observed when the PPI was withdrawn. CONCLUSIONS: Acid reflux directly causes sleep disturbances in rats with chronic esophagitis.

Significant association between hypolipoproteinemia(a) and lifetime risk of cancer: an autopsy study from a community-based Geriatric Hospital.

BACKGROUND: Our recent study showed that a low lipoproteinemia(a) [Lp(a)] level was a risk factor for cancer and all-cause deaths. The purpose of this study was to verify the role of the Lp(a) level on cancer among consecutive autopsy cases. METHODS: The subjects consisted of 1354 cases (775 men and 579 women). The average age at death was 79.9 years. Hypolipoproteinemia(a) was defined as an Lp(a) level of below 80 mg/L. Overall, 62.3% of the subjects had suffered from at least one to a maximum of five malignancies throughout their lives. The most frequent type of malignancy was gastric cancer, followed by leukemia, lung cancer, and colon cancer. RESULTS: The cancer-bearing status decreased linearly according to the Lp(a) level in both men and women (P=0.01 and P<0.001, respectively). The median Lp(a) level was significantly lower among the cases with hepato-biliary-pancreatic cancers or hematopoietic malignancy, but was higher among cases with lung cancer, especially lung adenocarcinoma. Hypolipoproteinemia(a) was a significant risk factor for any origins of cancer, with an odds ratio of 1.94 (95% CI, 1.45-2.60; P<0.001). It was also a risk factor for hepato-biliary cancers and leukemia, but it was a protective factor for lung cancer. CONCLUSIONS: Our findings suggested hypolipoproteinemia(a) would be a significant risk factor for cancer except lung cancer. This study complements our previous study showing that hypolipoproteinemia(a) would increase the lifetime risk of cancer other than lung cancer.

Low lipoprotein(a) concentration is associated with cancer and all-cause deaths: a population-based cohort study (the JMS cohort study).

BACKGROUND: Experimental studies support the anti-neoplastic effect of apo(a), but several clinical studies have reported contradictory results. The purpose of this study was to determine whether a low lipoprotein(a) [Lp(a)] concentration is related to mortality from major causes of death, especially cancer. METHODS: The subjects were 10,413 participants (4,005 men and 6,408 women) from a multi-center population-based cohort study in Japan (The Jichi Medical School cohort study). The average age at registration was 55.0 years, and the median observation period was 4,559 days. As the estimated hazard ratio was high for both the low and very high Lp(a) levels, we defined two Lp(a) groups: a low Lp(a) group [Lp(a)<80 mg/L] and an intermediate-to-high Lp(a) group [Lp(a) ≥ 80]. Participants who died from malignant neoplasms (n = 316), cardiovascular disease (202), or other causes (312) during the observation period were examined. RESULTS: Cumulative incidence plots showed higher cumulative death rates for the low Lp(a) group than for the intermediate-to-high Lp(a) group for all-cause, cancer, and miscellaneous-cause deaths (p<0.001, p = 0.03, and p = 0.03, respectively). Cox proportional hazards analyses with the sex and age of the participants, body mass index, and smoking and drinking histories as covariates showed that a low Lp(a) level was a significant risk for all-cause, cancer, and miscellaneous-cause deaths (p<0.001, p = 0.003, and p = 0.01, respectively). The hazard ratio (95% CI) [1.48, 1.15-1.92] of a low Lp(a) level for cancer deaths was almost the same as that for a male sex (1.46, 1.00-2.13). CONCLUSIONS: This is the first report to describe the association between a low Lp(a) level and all-cause or cancer death, supporting the anti-neoplastic effect of Lp(a). Further epidemiological studies are needed to confirm the present results.

Replication of the association between a chromosome 9p21 polymorphism and coronary artery disease in Japanese and Korean populations.

Coronary artery disease (CAD) has become a major health problem in many countries. Recent genome-wide association studies have identified the association between rs1333049 on chromosome 9p21 and susceptibility to CAD in Caucasoid populations. In this study, we evaluated the associations of rs1333049 with CAD in Japanese (604 patients and 1,151 controls) and Koreans (679 patients and 706 controls). We found a significant association in both Japanese [odds ratio (OR)=1.30, 95% confidence interval (CI); 1.13-1.49, p=0.00027, allele count model] and Koreans (OR=1.19, 95% CI; 1.02-1.38, p=0.025, allele count model). These observations demonstrated that chromosome 9p21 was the susceptibility locus for CAD also in East Asians.

Interaction of BMP10 with Tcap may modulate the course of hypertensive cardiac hypertrophy.

Elevated wall stress by hypertension induces an adaptive myocardial hypertrophy via releasing prohypertrophic hormones such as angiotensin II. In this study, we investigated the involvement of bone morphogenetic protein-10 (BMP10) in hypertension-induced cardiac hypertrophy. Expression of BMP10 was increased in the hypertrophied ventricles from hypertensive rats. BMP10 localized on cell surface and at stretch-sensing Z disc of cardiomyocytes, where BMP10 interacted with a protein called titin-cap (Tcap). A rare variant of the human BMP10 gene, Thr326Ile, was found to be associated with hypertensive dilated cardiomyopathy. The variant BMP10 demonstrated decreased binding to Tcap and increased extracellular secretion. Conditioned medium from cells transfected with wild-type or variant BMP10 induced hypertrophy in rat neonatal cardiomyocytes, except that medium from variant BMP10-carrying cells showed an enhanced effect reflecting the increased secretion. These observations suggested that hypertension induced expression of prohypertrophic BMP10, and the hypertrophic effect of BMP10 was modulated, at least in part, by its binding to Tcap at the Z disc.

Sustained progression and loss of the gender-related difference in atherosclerosis in the very old: a pathological study of 1074 consecutive autopsy cases.

INTRODUCTION: Epidemiological surveys show decrease or reversal of male predominance in cardiovascular mortality in the very old, but the actual condition of atherosclerosis in the very old is largely unknown. The objective of this paper is to reveal whether the atherosclerosis continues to progress, or the gender-related difference exists in the very old. METHODS: The subjects were 1074 consecutive autopsy cases of in-hospital death. The male:female ratio was 1.1:1 and the average age was 80 years. Macroscopic evaluation was performed on the degree of atherosclerosis in 10 arteries including the intracranial arteries, carotid artery, aorta, coronary artery, and femoral artery. RESULTS: The severity of atherosclerosis differed greatly among arteries. The age-related increase of the atherosclerotic degree was evident, even after 80 years of age. The atherosclerosis was more severe in males than in females in their 60s, but this male predominance decreased with ageing and finally disappeared in their 90s. CONCLUSION: The sustained progression of atherosclerosis and loss of the gender-related difference probably account for the increase of cardiovascular mortality in very old females. They also suggest that the prevention of the atherosclerotic progression is still important in the seventh and eighth decade of life.

Aortic pulse wave velocity and the degree of atherosclerosis in the elderly: a pathological study based on 304 autopsy cases.

INTRODUCTION: Studies examining the correlation between aortic pulse wave velocity (PWV) and atherosclerosis have reported conflicting results. The present paper verifies this correlation by conducting autopsy examination of elderly subjects. METHODS: A total of 3456 PWV examinations had been performed on 1538 elderly people, as a part of routine physical check-up. During long-term follow-up, many of these subjects died, and autopsy study could be conducted on 304 of these subjects. The average age at death of the subjects was 83 years and the male: female ratio was 6:5. The pathological atherosclerotic index (PAI) was defined as the average pathological degree of atherosclerosis in eight large arteries, including aorta. RESULTS: Significant positive correlations were observed between the age and PWV (gamma=0.273, P<0.001), and between the systolic blood pressure and PWV (gamma=0.478, P<0.001). There was a significantly positive correlation between the aortic atherosclerotic degree and mean PWV (rho=0.239, P<0.005), and between the PAI and mean PWV (gamma=0.323, P<0.001). The partial regression coefficient between the PAI and mean PWV was 0.209, after adjusting for the mean systolic blood pressure and age at death. CONCLUSION: The present study proved a weak correlation between the PWV and the pathologically verified degree of the aortic and systemic atherosclerosis.

Developments of geriatric autopsy database and Internet-based database of Japanese single nucleotide polymorphisms for geriatric research (JG-SNP).

To facilitate geriatric research on the roles of genetic polymorphisms of candidate genes, two databases were developed based on data obtained from autopsy examinations of elderly subjects: the geriatric autopsy database (GEAD) and the Japanese single nucleotide polymorphisms (SNP) database for geriatric research (JG-SNP) which is accessible on the Internet (http://www.tmgh.metro.tokyo.jp/jg-snp/english/E_top.html). The data for the GEAD were derived from 1074 consecutive autopsy cases (565 male and 509 female cases) with an average age of 80 years. The GEAD was installed on a stand-alone Windows 2000 server using Oracle 8i as the database application. The GEAD contains clinical diagnoses of 26 geriatric diseases, histories of smoking and alcohol consumption, pathological findings (720 items), severity of atherosclerosis, genetic polymorphism data, etc. On the JG-SNP website, case distribution corresponding to a specified SNP or disease can be searched or downloaded. Although there are several Internet-based SNP databases such as dbSNP, no databases are available at present on the web that contain both SNP data and phenotypic data. As autopsy studies can provide large amounts of accurate medical information, including the presence of undiagnosed diseases such as latent cancers, the GEAD is a unique and excellent database for research on genetic polymorphisms.

Association of estrogen receptor alpha gene polymorphisms with neurofibrillary tangles.

Estrogen receptor alpha (ERalpha) may be implicated in the pathogenesis of Alzheimer's disease (AD). The aim of this study was to clarify the association between ERalpha gene polymorphisms and AD-related pathologic changes. The staging of neurofibrillary tangles (NFT) and senile plaques (SP) was performed according to the method by Braak and Braak and two polymorphisms, PvuII (P or p) and XbaI (X or x), of the ERalpha gene were typed in 551 Japanese cadavers (294 men and 257 women; mean age, 80.8 years). Distributions of the NFT and SP stages significantly correlated with age (NFT: r = 0.306, p < 0.0001; SP: r = 0.237, p < 0.0001) and were significantly higher in patients with the apolipoprotein E epsilon4 allele (p < 0.0001). Possession of the P allele showed a trend to be associated with a more serious NFT stage, but had no relationship with the SP stage. In men, a significant association between PvuII polymorphism and the NFT stage (p = 0.002) was found, revealing a gene- dose effect of the P allele. Similar results were obtained in the men without the epsilon4 allele (p = 0.011). Multiple regression analyses demonstrated that age was the strongest determinant of the NFT stage, possession of the epsilon4 allele was the next strongest, and PvuII polymorphism was the third strongest (p < 0.0001, R(2) = 0.144). The XbaI polymorphism did affect neither the NFT stage nor the SP stage. In conclusion, the PvuII polymorphism of the ERalpha gene is associated with Braak NFT stages and possession of the P allele may act as a risk factor for AD in Japanese men, especially in those without the epsilon4 allele.

[Terminal care viewed from care-provider versus general population].

In an era of global aging, the care for the aged is one of the major societal concern. The comprehensive geriatric assessment (CGA) has proved to be a rational innovation to take care of the aged with impaired mental function and/or low activity of daily living. On the other hand, the reasonable attitude and philosophy for providing care for patients in terminal state is not settled. For example, there are least agreements on the terminal period, desirable place of death, living will of dementia patient, futile or under-therapy, and life support at death. In cancer patients, these problems have been practically resolved. Because there are many similarities between the management of elderly patients with CGA and that of patients with terminal state, CGA should be applied for all patients in terminal state with diseases besides malignancy. From the questionnaire to care-provider and general population, various opinions and many differences were observed between these two groups. Briefly, the opinions of care-provider were more reserved than that of general population. However, more than 70% of both groups were unanimous in that the present terminal care should be reformed. Otherwise, considering the diverse opinions for the terminal for the the aged, serious discussions and suitable studies on terminal care are required for fulfilling rest of life and peaceful death of aged people.