搜索结果：Internal medicine (Tokyo, Japan)

The coronavirus disease (COVID-19) pandemic has aggravated anxiety and depression worldwide, particularly in patients with chronic illnesses and mental disorders. Using validated questionnaires, in this paper, we examine the psychological effects of the pandemic in Japan in detail. The General Mental Health Scale (GHQ), the State-Trait Anxiety Inventory (STAI), and the Center for Epidemiologic Studies Depression Scale (CES-D) were used to assess mental health, state and trait anxiety, and depression, respectively. The survey was completed during the patients' first visits to the clinic of Psychosomatic Internal Medicine from November 2018 to April 2021. The Mann-Whitney U test was used to compare data from 226 participants before and during the COVID-19 pandemic. The GHQ total, GHQ subscales of "social dysfunction" and "anxiety and dysphoria", and state anxiety scores were significantly higher during than before the pandemic. The GHQ total, some GHQ subscales, and state anxiety scores were significantly higher among male than female participants during the pandemic. The GHQ total, some GHQ subscales, CES-D, and state anxiety scores in those aged 10-39 years were significantly higher. Thus, the COVID-19 pandemic may have caused mental health changes in many individuals based on their gender, age, and with time.

There have been few reports published in English on emergency medicine (EM) in Japan; the main reason for this is that the concept of EM was different in Japan from that in western countries. In the 1960s, legislation was passed in Japan that implemented emergency medical services, and emergency hospitals were designated by the government. There were no emergency medicine specialists, and so surgeons/physicians without specialist training in emergency medicine provided care to emergency patients (the multispecialist-type model). The Japanese Association for Acute Medicine (JAAM), an academic society for emergency physicians, was founded in 1973. In its pioneering days, this association focused mostly on trauma/burn care and also influenced policymaking. In 1977, the government built emergency medical service centers (the ICU-type model) and reorganized all emergency medical facilities into three levels. With the aging of society, the number of non-trauma patient! s presenting at hospitals, especially in the elderly population, has increased and has resulted in some cases of refusal by hospitals to accept emergency patients. A new postgraduate medical education curriculum was legislated in 2004 that mandated EM training for all postgraduates and encouraged reinforcement of emergency departments in teaching hospitals. The JAAM established a committee to promote the ER-type model of EM in 2003. By 2007, more than 150 JAAM-affiliated hospitals had implemented this type of EM. In conclusion, emergency medicine in Japan is currently based on a mixture of three models: the multispecialist-type, the ICU-type and the ER-type models.

This report is the collective product of word-leading experts working in the branches of integrative medicine by predictive, preventive and personalised medicine (PPPM) under the coordination of the European Association for Predictive, Preventive and Personalised Medicine. The general report has been prepared as the consortium document proposed at the EPMA World Congress 2011 which took place in Bonn, Germany. This forum analyzed the overall deficits and trends relevant for the top-science and daily practice in PPPM focused on the patient. Follow-up consultations resulted in a package of recommendations for consideration by research units, educators, healthcare industry, policy-makers, and funding bodies to cover the current knowledge deficit in the field and to introduce integrative approaches for advanced diagnostics, targeted prevention, treatments tailored to the person and cost-effective healthcare.

OBJECTIVE: The objective of this review was to update evidence-based medicine recommendations for treating motor symptoms of Parkinson's disease (PD). BACKGROUND: The Movement Disorder Society Evidence-Based Medicine Committee recommendations for treatments of PD were first published in 2002 and updated in 2011, and we continued the review to December 31, 2016. METHODS: Level I studies of interventions for motor symptoms were reviewed. Criteria for inclusion and quality scoring were as previously reported. Five clinical indications were considered, and conclusions regarding the implications for clinical practice are reported. RESULTS: A total of 143 new studies qualified. There are no clinically useful interventions to prevent/delay disease progression. For monotherapy of early PD, nonergot dopamine agonists, oral levodopa preparations, selegiline, and rasagiline are clinically useful. For adjunct therapy in early/stable PD, nonergot dopamine agonists, rasagiline, and zonisamide are clinically useful. For adjunct therapy in optimized PD for general or specific motor symptoms including gait, rivastigmine is possibly useful and physiotherapy is clinically useful; exercise-based movement strategy training and formalized patterned exercises are possibly useful. There are no new studies and no changes in the conclusions for the prevention/delay of motor complications. For treating motor fluctuations, most nonergot dopamine agonists, pergolide, levodopa ER, levodopa intestinal infusion, entacapone, opicapone, rasagiline, zonisamide, safinamide, and bilateral STN and GPi DBS are clinically useful. For dyskinesia, amantadine, clozapine, and bilateral STN DBS and GPi DBS are clinically useful. CONCLUSIONS: The options for treating PD symptoms continues to expand. These recommendations allow the treating physician to determine which intervention to recommend to an individual patient. © 2018 International Parkinson and Movement Disorder Society.

The Japanese traditional herbal medicine, Kampo, has gradually reemerged and 148 different formulations (mainly herbal extracts) can be prescribed within the national health insurance system. The objective of this article is to introduce Kampo and to present information from previous clinical studies that tested Kampo formulae. In addition, suggestions on the design of future research will be stated. The literature search was based on a summary, up until January 2009, by the Japanese Society of Oriental Medicine and included only those trials which were also available in either Pubmed or ICHUSHI (Japan Medical Abstracts Society). We included 135 studies, half of these studies (n = 68) used a standard control and 28 a placebo control. Thirty-seven trials were published in English [all randomized controlled trials (RCTs)] and the remaining articles were in Japanese only. The sample size for most studies was small (two-third of the studies included less than 100 patients) and the overall methodological quality appeared to be low. None of the studies used Kampo diagnosis as the basis for the treatment. In order to evaluate Kampo as a whole treatment system, certain aspects should be taken into account while designing studies. RCTs are the appropriate study design to test efficacy or effectiveness; however, within the trial the treatment could be individualized according to the Kampo diagnosis. Kampo is a complex and individualized treatment with a long tradition, and it would be appropriate for further research on Kampo medicine to take this into account.

Specific absorbed fraction (PHI's) in various organs of the body (target organs) from sources of monoenergetic photons in various other organs (source organs) are tabulated. In this volume PHI-values are tabulated for a newborn or 3.4-kg person. These PHI-values can be used in calculating the photon component of the dose-equivalent rate in a given target from a given radionuclide that is present in a given source organ. The International Commission on Radiological Protection recognizes that the endosteal, or bone surface, cells are the tissue at risk for bone cancer. We have applied the dosimetry methods that Spiers and co-workers developed for beta-emitting radionuclides deposited in bone to follow the transport of secondary electrons that were freed by photon interactions through the microscopic structure of the skeleton. With these methods we can estimate PHI in the endosteal cells and can better estimate PHI in the active marrow; the latter is overestimated with other methods at photon energies below 200 keV. 12 refs., 2 tabs.

BACKGROUND: The use of complementary and alternative medicine (CAM) has been increasing rapidly throughout the world during the past decade. The use of CAM in the general Japanese population has been previously reported to be as high as 76%. This study aims to investigate the patterns of CAM use, perceived effectiveness and disclosure of CAM use to orthodox medical practitioners amongst patients attending typical primary and secondary care clinics in a busy district general hospital in Tokyo, Japan. METHODS: The authors analysed data collected during March 2002 on patients attending general outpatient clinics held at Shiseikai Daini Hospital in Tokyo, Japan. Data was collected by use of self-completed questionnaires distributed to patients in the outpatient clinics waiting area. Statistical analysis was performed using chi-square tests of independence. RESULTS: 515 adults were approached to participate in this study and the overall response rate was 96% (n = 496). 50% of the patients were using or have used at least 1 CAM therapy within the last 12 months. The 5 most commonly used therapies were massage (n = 106, 43%), vitamins (n = 85, 35%), health foods including dietary supplements (n = 56, 23%), acupressure (n = 51, 21%) and kampo (n = 46, 19%). The majority of CAM users (75%, n = 145) found their CAM treatment to be effective (95% CI = 68-81%). Patients who were more likely to use CAM were females (p = 0.003) and those with a high number of medical conditions (p = < 0.0001). Only a small proportion of patients reported their CAM use to their physician (42%, n = 74). There was no significant difference in CAM use for the different age groups (p = 0.85), education level (p = 0.30) and financial status (p = 0.82). CONCLUSION: Patterns of CAM usage in the sample surveyed was high (50%). Despite this high prevalence rate and presumed acceptance of CAM in Japan, the reporting of CAM use by patients to their physicians was low (42%). It is therefore important that physicians are aware of the possibility that their patients may be using CAM and also increase their knowledge and understanding of these treatments.

In 2003, a lump-sum payment system based on Diagnosis Procedure Combinations (DPC) was introduced to 82 specific function hospitals in Japan. While the US DRG/PPS system is a "per case payment" system, the DPC based payment system adopts a "per day payment." It is generally believed that the Japanese system provides as much of an incentive as the DRG/PPS system to shorten the average length of stay (LOS). We performed an empirical analysis of the effect of LOS shortening on hospital revenue and expenditure under the DPC-based payment system, particularly in cardiovascular diseases. We also point out fundamentally controversial aspects of the current system. A total 109 cases were selected from patients hospitalized at the University of Tokyo Hospital from May to July, 2003 and classified into one of three categories: (1) cardiac catheter interventions, (2) cardiac catheter examinations, and (3) other conservative treatments. We analyzed the changes in profit per day in cases of a reduction in average LOS and an increase in the number of cases. In category (1) profit increased significantly in conjunction with reduced LOS. In category (2) profit increased only minimally. In category (3), profit increased rarely and sometimes decreased. In cases of conservative treatment, profits sometimes decreased because an increase in material costs exceeded the increase in revenue. It therefore became clear that the DPC-based payment system does not decisively provide an economic incentive to reduce LOS in cardiovascular medicine.

BACKGROUND: Rikkunshito, a traditional Japanese (Kampo) medicine, is widely prescribed as an oral preparation for the treatment of functional dyspepsia (FD). In our previous study, we reported that extracorporeal ultrasonography (US) is a useful technique for the assessment of the gastric accommodation reflex (AR) and duodenogastric motility. In this study, we examined the effects of Rikkunshito on the gastroduodenal function in patients with FD. METHODS: Sixteen FD patients (median age, 45 y) underwent US, before and after 14 days of treatment with Rikkunshito (7.5 g b.d.). For assessment of the AR, a cross-sectional area of the proximal stomach was measured after incremental ingestion of a liquid meal up to 400-mL. The expansion rate was used as the parameter to determine the AR. Then, the gastric emptying rate (GER), motility index (MI), and reflux index (RI) were evaluated using previously reported methods. RESULTS: Although no significant changes were observed in the total score of the Gastrointestinal Symptom Rating Scale (GSRS), the scores of 3 of the 15 symptoms of GSRS decreased significantly after treatment with Rikkunshito. The expansion rate of the proximal stomach was significantly greater after treatment with Rikkunshito than before the treatment. Although the GER and MI increased significantly, no significant differences in the RI were observed after treatment with Rikkunshito. CONCLUSION: These observations suggested that Rikkunshito may be beneficial for the treatment of FD patients with impaired AR and gastric motility. These results also suggested that Rikkunshito has a therapeutic potential for FD and GERD.

To the Editor: In 2010, the International Consensus Diagnostic Criteria (ICDC) for autoimmune pancreatitis (AIP) were proposed to address the pathogenesis, clinical features, and treatment of AIP on a global level.1 The ICDC were the first to enable the diagnosis and comparison of the 2 distinctive subtypes of AIP: type 1 and type 2. Because the diagnosis of AIP in Western countries was based mainly on pathological findings using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in contrast to the Japanese diagnostic procedures giving priority to image findings using endoscopic retrograde pancreatography (ERP) especially for differentiation from pancreatic cancer, the ICDC were exempt from the ERP procedure, whereas previous Japanese diagnostic criteria and Asian criteria required it.2–4 The ICDC also adopted the diagnostic item of steroid therapy effectiveness as a treatment option. However, the ICDC were somewhat complicated for general use, and extremely few cases of type 2 AIP have been confirmed in Japan. Accordingly, the Japan Pancreas Society (JPS) and the Research Program on Intractable Disease from the Ministry of Labor, Health, and Welfare of Japan (RPID-MLHWJ) amended the ICDC into the Japanese clinical diagnostic criteria for AIP 2011 (JPS2011), which adhered closely to the basic concepts of the ICDC.5,6 The JPS2011 incorporated elements of both the previous Japanese criteria and type 1 AIP in the ICDC as much as possible and was designed to be simple for general physician use. The JPS2011 included: (1) diffuse/segmental/focal classification on pancreatic imaging; (2) IgG4 alone as a serological marker; (3) sclerosing cholangitis, sclerosing sialadenitis, and retroperitoneal fibrosis as other organ involvement (OOI); (4) no classifications of level 1/2 in serum IgG4 or OOI; and (5) optional steroid trial only after excluding malignancy by EUS-FNA. Endoscopic retrograde pancreatography was basically required for focal/segmental type AIP, but not for the typical diffuse type. Magnetic resonance cholangiopancreatography (MRCP) was not an item in the JPS2011 due to inadequate resolution at the time. Because the diagnostic use of ERP is limited in Japan and the quality of MRCP images has improved recently, JPS and RPID-MLHWJ have proposed revision of the JPS2011 mainly to establish a procedure that includes MRCP and negative findings of malignancy by EUS-FNA to complement the diagnostic ability of ERP. In 2018, a report entitled “Japanese Clinical Diagnostic Criteria for Autoimmune Pancreatitis, 2018: Revision of Japanese Clinical Diagnostic Criteria for Autoimmune Pancreatitis 2011” was published in Suizo, the official journal of the JPS.7 To better understand the Japanese clinical picture in AIP diagnosis, we herein introduce the English version of the JPS2018: Revision of the JPS2011 (Supplemental Table 1, https://links.lww.com/MPA/A751) in Pancreas, the official journal of JPS and American Pancreas Association, with the permission of the respective Editors-in-Chief of Suizo and Pancreas, Professors Sata and Go. Because advancements in MRI, such as 3T units, have rendered the image quality of MRCP nearly equivalent to that of ERP, MRCP is now considered to complement ERP to some extent and has been included in diagnostic procedures. The diagnostic criteria of “II. Image findings showing irregular narrowing of the main pancreatic duct” have been divided into ERP and MRCP, and a statement on MRCP findings was added to the Explanations section as “Narrowing or invisibleness of the main pancreatic duct is seen on MRCP and is extended to a certain degree, sometimes appearing as a multiple skip lesion. No significant dilation is observed above the narrowed area upstream of the main duct. It is usually difficult to evaluate side branches arising from narrowed portions of the main pancreatic duct. Although image quality of MRCP depends on the MR unit and scan parameters, it is necessary to acquire sufficient good quality images for the detailed evaluation of the pancreatic duct.” In addition, the item of “No neoplastic cells detected by EUS-FNA” was added to the section of “IV. Pathological finding” to indicate negative findings of malignancy by EUS-FNA as IVc. Regarding diagnostic ability, ERP was adjusted to be equivalent to the combination of MRCP and IVc (negative findings of malignancy by EUS-FNA) in the diagnostic procedure. Many RPID-MLHWJ and JPS members have expressed difficulty in excluding malignancy by EUS-FNA. Even so, at the time of EUS-FNA, negative findings of malignancy combined with other results, such as elevated serum IgG4 and OOIs, are able to identify the possibility of AIP. To clarify this, we have added the following statement to the section “IV. Pathological findings of the pancreas”: “Although EUS-FNA is a useful tool to exclude cancer, the absence of neoplastic cells alone is insufficient; it is also important to exclude cancer using the image findings shown in I-2). Moreover, the diagnostic process should be done carefully, with comprehensive evaluation of serological findings and other organ involvement.” Additionally, useful image findings to differentiate between AIP and pancreatic cancer were proposed by a radiological committee and incorporated into the section of “I. Enlarged pancreas” as “Abdominal CT▪MRI: It is recommended to perform dynamic contrast-enhanced CT▪MRI with bolus injection of contrast medium wherever possible. Useful findings for differentiation from pancreatic cancer are speckled/dotted enhancement and capsule-like rim at the parenchymal phase as well as delayed homogeneous enhancement. Capsule-like rim is seen as a band-like low-intensity area on T2-weighed images. Duct-penetrating sign is another characteristic finding of focal AIP and is rarely seen,” as well as “Even when characteristic findings for AIP can be found, careful diagnostic procedures should be conducted to exclude the possibility of pancreatic cancer if concurrent findings suggestive of cancer are present, such as upstream dilation of the main pancreatic duct, heterogeneous delayed enhancement, or severe stenosis of involved arteries.” As kidney lesion was already included as an OOI in the ICDC, it seemed logical to add it to the OOI list of the JPS2011, which also contained sclerosing cholangitis, sclerosing dacryoadenitis/sialadenitis, and retroperitoneal fibrosis. The JPS2018 revisions are expected to improve diagnostic accuracy for AIP and enable earlier disease identification and treatment. Shigeyuki Kawa, MD, PhD Department of Internal Medicine Matsumoto Dental University Shiojiri, Japan [email protected]Terumi Kamisawa, MD, PhD Department of Internal Medicine Tokyo Metropolitan Komagome Hospital Tokyo, JapanKenji Notohara, MD, PhD Department of Anatomic Pathology Kurashiki Central Hospital Kurashiki, JapanYasunari Fujinaga, MD, PhD Department of Radiology Shinshu University School of Medicine Matsumoto, JapanDai Inoue, MD, PhD Department of Radiology Kanazawa University Graduate School of Medical Science Kanazawa, JapanTakashi Koyama, MD, PhD Department of Diagnostic Radiology Kurashiki Central Hospital Kurashiki, JapanKazuichi Okazaki, MD, PhD Department of Gastroenterology and Hepatology Kansai Medical University Osaka Osaka, Japan On behalf of the Working Group Members of the Japan Pancreas Society and The Research Program on Intractable Diseases from the Ministry of Labor and Welfare of Japan

// Shin Nishiumi 1, * , Takashi Kobayashi 1, * , Shuichi Kawana 2 , Yumi Unno 2 , Takero Sakai 2 , Koji Okamoto 3 , Yasuhide Yamada 4 , Kazuki Sudo 4 , Taiki Yamaji 5 , Yutaka Saito 6 , Yukihide Kanemitsu 7 , Natsuko Tsuda Okita 4 , Hiroshi Saito 8 , Shoichiro Tsugane 9 , Takeshi Azuma 1 , Noriyuki Ojima 2 , Masaru Yoshida 1, 10, 11 &ensp;1 Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo 650-0017, Japan &ensp;2 Analytical and Measuring Instruments Division, Shimadzu Corporation, Nakagyo-ku, Kyoto 604-8511, Japan &ensp;3 Division of Cancer Differentiation, National Cancer Center Research Institute, Tokyo 104-0045, Japan &ensp;4 Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan &ensp;5 Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan &ensp;6 Endoscopy Division, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan &ensp;7 Department of Colorectal Surgery, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan &ensp;8 Division of Screening Assessment and Management, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan &ensp;9 Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan 10 Division of Metabolomics Research, Department of Internal Related, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo 650-0017, Japan 11 AMED-CREST, AMED, Chuo-ku, Kobe, Hyogo 650-0017, Japan * These authors have contributed equally to this work Correspondence to: Masaru Yoshida, email: myoshida@med.kobe-u.ac.jp Keywords: metabolomics, colorectal cancer, biomarker, gas chromatography/triple-quadrupole mass spectrometry, metabolite Received: November 14, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: January 09, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: February 04, 2017 ABSTRACT In developed countries, the number of patients with colorectal cancer has been increasing, and colorectal cancer is one of the most common causes of cancer death. To improve the quality of life of colorectal cancer patients, it is necessary to establish novel screening methods that would allow early detection of colorectal cancer. We performed metabolome analysis of a plasma sample set from 282 stage 0/I/II colorectal cancer patients and 291 healthy volunteers using gas chromatography/triple-quadrupole mass spectrometry in an attempt to identify metabolite biomarkers of stage 0/I/II colorectal cancer. The colorectal cancer patients included patients with stage 0 (N=79), I (N=80), and II (N=123) in whom invasion and metastasis were absent. Our analytical system detected 64 metabolites in the plasma samples, and the levels of 29 metabolites differed significantly (Bonferroni-corrected p=0.000781) between the patients and healthy volunteers. Based on these results, a multiple logistic regression analysis of various metabolite biomarkers was carried out, and a stage 0/I/II colorectal cancer prediction model was established. The area under the curve, sensitivity, and specificity values of this model for detecting stage 0/I/II colorectal cancer were 0.996, 99.3%, and 93.8%, respectively. The model&rsquo;s sensitivity and specificity values for each disease stage were &gt;90%, and surprisingly, its sensitivity for stage 0, specificity for stage 0, and sensitivity for stage II disease were all 100%. Our predictive model can aid early detection of colorectal cancer and has potential as a novel screening test for cases of colorectal cancer that do not involve lymph node or distant metastasis.

// Shoji Yamada 1 , Yoko Takashina 2 , Mitsuhiro Watanabe 2 , Ryogo Nagamine 1 , Yoshimasa Saito 1, 3 , Nobuhiko Kamada 4 and Hidetsugu Saito 1, 3 1 Division of Pharmacotherapeutics, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan 2 Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-0882, Japan 3 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan 4 Division of Gastroenterology, Department of Internal Medicine, The University of Michigan Medical School, Ann Arbor, MI, 48109, USA Correspondence to: Hidetsugu Saito, email: hsaito@a2.keio.jp Keywords: deoxycholic acid; bile acid metabolites; mTOR; hepatocellular carcinoma Received: April 28, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: November 20, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: January 06, 2018 ABSTRACT Gut microbiota plays a significant role in the development of hepatocellular carcinoma (HCC) in non-alcoholic steatohepatitis (NASH). However, understanding of the precise mechanism of this process remains incomplete. A new class steatohepatitis-inducing high-fat diet (HFD), namely STHD-01, can promote the development of HCC without the administration of chemical carcinogens. Using this diet, we comprehensively analyzed changes in the gut microbiota and its metabolic functions during the development of HCC in NASH. Mice fed the STHD-01 developed NASH within 9 weeks. NASH further progressed into HCC by 41 weeks. Treatment with antibiotics significantly attenuated liver pathology and suppressed tumor development, indicating the critical role of the gut microbiota in tumor development in this model. Accumulation of cholesterol and bile acids in the liver and feces increased after feeding the mice with STHD-01. Treatment with antibiotics did not reverse these phenotypes. In contrast, accumulation of secondary bile acids was dramatically reduced after the treatment with antibiotics, suggesting the critical role of the gut microbiota in the conversion of primary bile acids to secondary bile acids. Secondary bile acids such as deoxycholic acid activated the mTOR, pathway in hepatocytes. Activation of mTOR was observed in the liver of mice fed STHD-01, and the activation was reduced when mice were treated with antibiotics. Collectively, bile acid metabolism by the gut microbiota promotes HCC development in STHD-01-induced NASH.

1First Department of Internal Medicine Tokyo Medical and Dental University Tokyo, Japan Reprint requests and correspondence: Ryuji Koike, MD, The First Department of Internal Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan Received June 28, 1999; accepted July 2, 1999.

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies. Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics. The 1000 Genomes Project has sought to comprehensively catalogue human genetic variation across populations, providing a valuable public genomic resource. The data obtained so far have found applications ranging from association studies and fine mapping studies to the filtering of likely neutral variants in rare-disease cohorts. The authors now report on the final phase of the project, phase 3, which covers previously uncharacterized areas of human genetic diversity in terms of the populations sampled and categories of characterized variation. The sample now includes more than 2,500 individuals from 26 global populations, with low coverage whole-genome and deep exome sequencing, as well as dense microarray genotyping. They find that while most common variants are shared across populations, rarer variants are often restricted to closely related populations. The authors also demonstrate the use of the phase 3 dataset as a reference panel for imputation to improve the resolution in genetic association studies.

Keio University Department of Plastic and Reconstructive Surgery School of Medicine 35 Shinanomachi, Shinjuku-ku Tokyo 160, Japan The blood supply of the nipple-areola complex was investigated radiographically in five fresh cadavers that had been systemically injected with lead oxide. The blood supply of the breast is derived from the external mammary, internal mammary, intercostal, and thoracoacromial arteries. We found that branches of the external and internal mammary arteries provided the dominant blood supply to the nipple-areola complex. These branches provide small vessels that traverse the subcutaneous tissue to the nipple-areola complex. Branches are given off to the areolar skin. These ascended, arborizing in the upper and middle thirds of the nipple. (Plast. Reconstr. Surg. 96: 843, 1995.)

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BACKGROUND: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. METHODS: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. FINDINGS: In 2019, there were 12·2 million (95% UI 11·0-13·6) incident cases of stroke, 101 million (93·2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6·55 million (6·00-7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8-12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1-6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0-73·0), prevalent strokes increased by 85·0% (83·0-88·0), deaths from stroke increased by 43·0% (31·0-55·0), and DALYs due to stroke increased by 32·0% (22·0-42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0-18·0), mortality decreased by 36·0% (31·0-42·0), prevalence decreased by 6·0% (5·0-7·0), and DALYs decreased by 36·0% (31·0-42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0-24·0) and incidence rates increased by 15·0% (12·0-18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5-3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5-3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57-8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97-3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01-1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7-90·8] DALYs or 55·5% [48·2-62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3-48·6] DALYs or 24·3% [15·7-33·2]), high fasting plasma glucose (28·9 million [19·8-41·5] DALYs or 20·2% [13·8-29·1]), ambient particulate matter pollution (28·7 million [23·4-33·4] DALYs or 20·1% [16·6-23·0]), and smoking (25·3 million [22·6-28·2] DALYs or 17·6% [16·4-19·0]). INTERPRETATION: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. METHODS: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). FINDINGS: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6-58·8) of global deaths and 41·2% (39·8-42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. INTERPRETATION: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. FUNDING: Bill & Melinda Gates Foundation.

Tokyo Metropolitan Komagome Hospital, Tokyo, Japan Reprint requests and correspondence: Terumi Kamisawa, MD, Tokyo Metropolitan Komagome Hospital, Department of Internal Medicine, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677 Tokyo, Japan. Received 12 August 2003; accepted 21 August 2003