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PubMed2026

Efficacy, Safety, and Pharmacokinetics of Upadacitinib Among Patients in East Asia With Moderately to Severely Active Ulcerative Colitis: A Post Hoc Subanalysis of Randomized Phase 3 Studies.

BACKGROUND AND AIM: Upadacitinib, a selective Janus kinase 1 inhibitor, is approved to treat moderately to severely active ulcerative colitis (UC). This post hoc subanalysis evaluated the efficacy, safety, and pharmacokinetics of upadacitinib in patients in East Asia. METHODS: U-ACHIEVE (UC1; NCT02819635) and U-ACCOMPLISH (UC2; NCT03653026) were Phase 3, multicenter, randomized, double-blind, induction studies evaluating upadacitinib 45 mg or placebo daily in adults with moderately to severely active UC. Clinical responders to 8 weeks of upadacitinib induction were eligible to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo daily in the 52-week U-ACHIEVE maintenance study (UC3; NCT02819635). Efficacy outcomes, safety, and pharmacokinetics were evaluated among East Asian patients. RESULTS: A higher proportion of East Asian patients achieved clinical remission with upadacitinib than placebo at induction Week 8 (UC1: n = 127, 31.4% vs. 7.3%; UC2: n = 114, 31.2% vs. 2.7%) and maintenance Week 52 (UC3: n = 184, upadacitinib 15 mg, 52.4%; upadacitinib 30 mg, 53.8%; placebo, 10.7%). Rates of endoscopic outcomes were higher with upadacitinib than with placebo across studies. No new safety signals were identified. Herpes zoster occurrences were low (UC1 and UC2: upadacitinib 45 mg, two events [in one patient]; placebo, zero events; UC3: upadacitinib 15 mg, five events; upadacitinib 30 mg, eight events; placebo, zero events). Pharmacokinetics and trends in the relationship between upadacitinib exposure and efficacy were consistent in the East Asian and global populations. CONCLUSION: Upadacitinib was generally well tolerated and effective for treating moderately to severely active UC in patients in East Asia, with a favorable benefit-risk profile consistent with the global population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02819635, NCT03653026.

Humans↗
PubMed2001

African origin of modern humans in East Asia: a tale of 12,000 Y chromosomes.

To test the hypotheses of modern human origin in East Asia, we sampled 12,127 male individuals from 163 populations and typed for three Y chromosome biallelic markers (YAP, M89, and M130). All the individuals carried a mutation at one of the three sites. These three mutations (YAP+, M89T, and M130T) coalesce to another mutation (M168T), which originated in Africa about 35,000 to 89,000 years ago. Therefore, the data do not support even a minimal in situ hominid contribution in the origin of anatomically modern humans in East Asia.

Africa↗
PubMed2005

Single, rapid coastal settlement of Asia revealed by analysis of complete mitochondrial genomes.

A recent dispersal of modern humans out of Africa is now widely accepted, but the routes taken across Eurasia are still disputed. We show that mitochondrial DNA variation in isolated "relict" populations in southeast Asia supports the view that there was only a single dispersal from Africa, most likely via a southern coastal route, through India and onward into southeast Asia and Australasia. There was an early offshoot, leading ultimately to the settlement of the Near East and Europe, but the main dispersal from India to Australia approximately 65,000 years ago was rapid, most likely taking only a few thousand years.

Africa↗
PubMed2004

Antimicrobial activities of garenoxacin (BMS 284756) against Asia-Pacific region clinical isolates from the SENTRY program, 1999 to 2001.

Between 1999 and 2001, 16,731 isolates from the Asia-Pacific Region were tested in the SENTRY Program for susceptibility to six fluoroquinolones including garenoxacin. Garenoxacin was four- to eightfold less active against Enterobacteriaceae than ciprofloxacin, although both drugs inhibited similar percentages at 1 microg/ml. Garenoxacin was more active against gram-positive species than all other fluoroquinolones except gemifloxacin. For Staphylococcus aureus, oxacillin resistance was high in many participating countries (Japan, 67%; Taiwan, 60%; Hong Kong, 55%; Singapore, 52%), with corresponding high levels of ciprofloxacin resistance (57 to 99%) in oxacillin-resistant S. aureus (ORSA). Of the ciprofloxacin-resistant ORSA isolates, the garenoxacin MIC was >4 microg/ml for only 9% of them. For Streptococcus pneumoniae, penicillin nonsusceptibility and macrolide resistance were high in many countries. No relationship was seen between penicillin and garenoxacin susceptibility, with all isolates being susceptible at <2 microg/ml. There was, however, a partial correlation between ciprofloxacin and garenoxacin MICs. For ciprofloxacin-resistant isolates for which garenoxacin MICs were 0.25 to 1 microg/liter, mutations in both the ParC and GyrA regions of the quinolone resistance-determining region could be demonstrated. No mutations conferring high-level resistance were detected. Garenoxacin shows useful activity against a wide range of organisms from the Asia-Pacific region. In particular, it has good activity against S. aureus and S. pneumoniae, although there is evidence that low-level resistance is present in those organisms with ciprofloxacin resistance.

Anti-Infective Agents↗
PubMed1983

Identification of enterotoxigenic Escherichia coli in patients with diarrhea in Asia with three enterotoxin gene probes.

A total of 984 enterotoxigenic Escherichia coli (ETEC) and 733 non-ETEC isolated from patients with diarrhea in Asia (one isolate per patient) were examined for homology with radiolabeled fragments of DNA encoding heat-labile toxin (LT) or heat-stable toxin of porcine (ST-P) or human (ST-H) origin. A total of 246 ETEC that produced LT and ST as determined by the Y-1 adrenal and suckling mouse assays were homologous with the LT probe. Of these 246 LTST ETEC, 156 (63%) were homologous with the ST-H, 46 (19%) were homologous with the ST-P, and 44 (18%) were homologous with both probes. A total of 401 LT ETEC were homologous with the LT probe. Of 337 ST ETEC identified by the suckling mouse assay, 244 (72%) were homologous with the ST-H, 84 (25%) were homologous with the ST-P, and 9 (3%) were homologous with both probes. None of the 733 isolates that were non-enterotoxigenic as determined by the Y-1 adrenal and suckling mouse assays was homologous with genes coding for enterotoxin. Four isolates (not included among the 984 ETEC examined) that were initially considered to produce LT because sterile culture supernatants produced rounding of Y-1 adrenal cells were not homologous with the LT probe. The sterile culture supernatants of these four isolates caused rounding after 8 h and subsequent destruction after 24 h of Y-1 adrenal tissue cultures. This effect was not inhibited by convalescent human cholera antiserum, Swiss Serum Institute cholera antitoxin, or antiserum to purified LT. These isolates were also negative in the Biken test previously used to identify LT-producing E. coli. The DNA hybridization technique with three enterotoxin gene probes was developed as a specific technique to identify ETEC in large numbers of specimens in Asia.

Animals↗
PubMed1995

Analysis of Salmonella typhi isolates from Southeast Asia by pulsed-field gel electrophoresis.

Pulsed-field gel electrophoresis (PFGE) revealed that multiple genetic variants of Salmonella typhi are simultaneously present in Southeast Asia and are associated with sporadic cases of typhoid fever and occasional outbreaks. Comparative analysis of PFGE patterns also suggested that considerable genetic diversity exists among S. typhi strains and that some PFGE patterns are shared between isolates obtained from Malaysia, Indonesia, and Thailand, implying movement of these strains within these regions of Southeast Asia, where they are endemic.

Asia, Southeastern↗
PubMed1996

Survey of type 6 group variants of hepatitis C virus in Southeast Asia by using a core-based genotyping assay.

Previous surveys of the prevalences of genotypes of hepatitis C virus (HCV) in different populations have often used genotyping assays based upon analysis of amplified sequences from the 5' noncoding region (5'NCR), such as restriction fragment length polymorphism (RFLP) or hybridization with type-specific probes (e.g., InnoLipa). Although highly conserved, this region contains several type-specific nucleotide polymorphisms that allow major genotypes 1 to 6 to be reliably identified. Recently, however, novel HCV variants found in Vietnam and Thailand that are distantly related to the type 6a genotype (type 6 group) by phylogenetic analysis of coding regions of the genome often have sequences in the 5'NCR that are similar or identical to those of type 1 and could therefore not be identified by an assay of sequences in this region. We developed a new genotyping assay based upon RFLP of sequences amplified from the more variable core region to investigate their distribution elsewhere in southeast (SE) Asia. Among 108 samples from blood donors in seven areas that were identified as type 1 by RFLP in the 5'NCR, type 6 group variants were found in Thailand (7 from 28 samples originally identified as type 1) and Burma (Myanmar) (1 of 3) but were not found in Hong Kong (n = 43), Macau (n = 8), Taiwan (n = 6), Singapore (n = 2), or Malaysia (n = 18). Although this small survey suggests a relatively limited distribution for type 6 group variants in SE Asia, larger studies will be required to explore their distribution in other geographical regions and the extent to which their presence would limit the practical usefulness of 5'NCR-based genotyping assays for clinical or epidemiological purposes.

Asia, Southeastern↗
PubMed1998

Epidemiological study of prevalence of genogroup II human calicivirus (Mexico virus) infections in Japan and Southeast Asia as determined by enzyme-linked immunosorbent assays.

Mexico virus (MXV) is a genogroup II human calicivirus (HuCV). We conducted an epidemiological study to determine the prevalence of MXV infection in infants and adults in Japan and Southeast Asia by enzyme-linked immunosorbent assays (ELISAs) developed by using baculovirus-expressed recombinant MXV (rMXV) capsids. Of 155 stool specimens obtained from children younger than 10 years old with acute clinical gastroenteritis (diarrhea and vomiting) associated with small, round-structured viruses in Japan from 1987 to 1989, only 2 were positive for MXV antigen. In 42 outbreaks of acute gastroenteritis in Japan from 1986 to 1994, 1 in an infant home and 1 among adults were positive for MXV antigen. The pattern of acquisition of antibody to rMXV was different from that of acquisition of antibody to group A rotavirus, the prototype HuCV Sapporo virus, and Norwalk virus. The prevalence of antibody to rMXV remained low for the first 3 years of life, showed a steep rise during nursery school age, reaching a prevalence of 50%, and another steep rise during adolescence, reaching 80%; and steadily increased thereafter. A high prevalence of antibody (82 to 88%) was observed in adult populations in Japan and Southeast Asia, suggesting that MXV infection is common in these areas. The discrepancy between the high prevalence of antibody to MXV and a low rate of detection of MXV antigen may be explained by a high specificity of the antigen ELISA for the prototype and closely related MXV strains while serological responses can detect responses to a broader group of viruses.

Adult↗
PubMed2004

Selection pressure-driven evolution of the Epstein-Barr virus-encoded oncogene LMP1 in virus isolates from Southeast Asia.

The geographically constrained distribution of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in southeast Asian populations suggests that both viral and host genetics may influence disease risk. Although susceptibility loci have been mapped within the human genome, the role of viral genetics in the focal distribution of NPC remains an enigma. Here we report a molecular phylogenetic analysis of an NPC-associated viral oncogene, LMP1, in a large panel of EBV isolates from southeast Asia and from Papua New Guinea, Africa, and Australia, regions of the world where NPC is and is not endemic, respectively. This analysis revealed that LMP1 sequences show a distinct geographic structure, indicating that the southeast Asian isolates have evolved as a lineage distinct from those of Papua New Guinea, African, and Australian isolates. Furthermore, a likelihood ratio test revealed that the C termini of the LMP1 sequences of the southeast Asian lineage are under significant positive selection pressure, particularly at some sites within the C-terminal activator regions. We also present evidence that although the N terminus and transmembrane region of LMP1 have undergone recombination, the C-terminal region of the gene has evolved without any history of recombination. Based on these observations, we speculate that selection pressure may be driving the LMP1 sequences in virus isolates from southeast Asia towards a more malignant phenotype, thereby influencing the endemic distribution of NPC in this region.

Amino Acid Sequence↗
PubMed2006

The epidemiology of age related eye diseases in Asia.

In the past decade, several large population based studies have provided new information on the prevalence of visual impairment and the major age related eye diseases in Asia. These include epidemiological studies from India, Taiwan, Mongolia, Singapore, and Japan. In particular, the epidemiology of refractive errors and glaucoma has been well characterised, providing insights not only into the public health implications of these conditions, but also into anatomical changes of the eye with ageing. In contrast, there are few well conducted population based studies on diabetic retinopathy and age related macular degeneration in Asia, two conditions that are likely to be important causes of blindness in the future.

Adult↗
PubMed1999

Retrospective analysis of census data on general practitioners who qualified in South Asia: who will replace them as they retire?

OBJECTIVES: To determine the number and geographical distribution of general practitioners in the NHS who qualified medically in South Asia and to project their numbers as they retire. DESIGN: Retrospective analysis of yearly data and projection of future trends. SETTING: England and Wales. SUBJECTS: General practitioners who qualified medically in the countries of Bangladesh, India, Pakistan, and Sri Lanka and who were practising in the NHS on 1 October 1992. MAIN OUTCOME MEASURES: Proportion and age of general practitioners who qualified in South Asia by health authority; the Benzeval and Judge measure of population need at the health authority level. RESULTS: 4192 of 25 333 (16.5%) of all unrestricted general practitioners practising full time on 1 October 1992 qualified in South Asian medical schools. The proportion varied by health authority from 0.007% to 56.5%. Roughly two thirds who were practising in 1992 will have retired by 2007; in some health authorities this will represent a loss of one in four general practitioners. The practices that these doctors will leave seem to be in relatively deprived areas as measured by deprivation payments and a health authority measure of population need. CONCLUSION: Many general practitioners who qualified in South Asian medical schools will retire within the next decade. The impact will vary greatly by health authority. Those health authorities with the greatest number of such doctors are in some of the most deprived areas in the United Kingdom and have experienced the most difficulty in filling vacancies. Various responses will be required by workforce planners to mitigate the impact of these retirements.

Asia↗
PubMed2004

Complicity in contraband: British American Tobacco and cigarette smuggling in Asia.

OBJECTIVES: To examine the complicity of British American Tobacco (BAT) in cigarette smuggling in Asia, and to assess the centrality of illicit trade to regional corporate strategy. METHODS: Analysis of previously confidential documents from BAT's Guildford depository. An iterative strategy combined searches based on geography, organisational structure, and key personnel, while corporate euphemisms for contraband were identified by triangulation. RESULTS: BAT documents demonstrate the strategic importance of smuggling across global, regional, national, and local levels. Particularly important in Asia, contraband enabled access to closed markets, created pressure for market opening, and was highly profitable. Documents demonstrate BAT's detailed oversight of illicit trade, seeking to reconcile the conflicting demands of control and deniability. CONCLUSIONS: BAT documents demonstrate that smuggling has been driven by corporate objectives, indicate national measures by which the problem can be addressed, and highlight the importance of a coordinated global response via WHO's Framework Convention on Tobacco Control.

Asia↗
PubMed1979

Geographical distribution of swine (Hsw1N1) and Hong Kong (H3N2) influenza virus variants in pigs in Southeast Asia.

Influenza viruses of the Hsw1N1 and H3N2 subtypes were isolated in Hong Kong from pigs originating from Hong Kong, People's Republic of China (PRC), Singapore, and Taiwan. The H3N2 isolates were from pigs from Hong Kong and PRC, whereas the Hsw1N1 isolates were from pigs from Hong Kong, PRC, Singapore and Taiwan. The hemagglutinins of the H3N2 isolates were similar to those of the earlier A/Hong Kong/1/68 and A/Port Chalmers/1/73 variants from man. The Hsw1N1 isolates were similar to the human A/New Jersey/8/76 virus. These studies extend the geographical range of Hsw1N1 influenza virus and suggest that pigs in southeast Asia, like those in North America, harbor Hsw1N1 influenza viruses. These findings underline the importance of pigs as potential reservoirs for future human pandemics by the continued isolation (in Asia) of H3N2 and Hsw1N1 influenza viruses.

Animals↗
PubMed2001

Mental health in Asia: social improvements and challenges.

Remarkable improvements in economic conditions and a considerable upgrade in the quality of life have been observed in many parts of Asia during the past several decades. At the same time, many mental health challenges face the people of Asia. Various social mental health indexes are reviewed here, with available data from China, Japan, Korea, Singapore, Malaysia, and other Asian societies. The data are compared with data from the United States, Australia in the Pacific Rim, and some other Western countries to examine patterns of similarity or difference between East and West in the process of modernization. Common trends in mental health issues associated with rapid sociocultural change observed in different Asian societies are discussed, as well as the relative shortage of mental health personnel available in many Asian societies. It is emphasized that, in addition to expanding psychiatric services, there is an even more urgent need to promote mental health knowledge and concern through education in the general population. Mental health needs to be cultivated and maintained by social forces and cultural strengths. It is stressed that there is a challenge for Asian people to advance mental health beyond economic development in the 21st century.

Asia↗
PubMed1992

The future of international migration within Asia.

"Data on flows from Asia to the Middle East and developing countries as well as on flows within Asia are presented, followed by a discussion of the growing importance of intraregional labor migration. Demographic pressures and widely varying economic growth rates will stimulate this movement and bring greater private and government agency participation. Female and family migration and settlement will be encouraged by geographic and cultural proximity. As intraregional labor migration becomes more institutionalized, governments face major policy challenges for planning, regulating and monitoring overseas employment; for the protection of migrant workers; and for stronger regional cooperation." Projections are made to the year 2025.

Asia↗
PubMed1998

The demographic underpinnings of current and future international migration in Asia.

"The present paper suggests that one element which needs to be considered in explaining contemporary international migration [in the Asia-Pacific region] but especially in anticipating trends over the next decade are the differential patterns of growth of population within the region. While population growth overall has slowed, the work force age groups will continue to grow rapidly in Asia over the next decade or so and the contrasts between individual countries will increase. The proportion in the peak mobility age groups will thus continue to grow rapidly in particular countries and will be one of the elements contributing to increased levels of international migration within and out of the region."

Asia↗
PubMed2002

Towards a comparative analysis of health systems reforms in the Asia-Pacific Region.

The paper will review a representative selection of health systems reforms throughout the Asia-Pacific region to summarise the regional experience, identify the key lessons learnt from innovative health reforms and propose policy recommendations for sustainable health systems development. Broad descriptive trends of health systems reforms will be compared across the Asia-Pacific region within the context of rapid demographic, health and socio-economic development. More specifically, the study will address the following questions: 1. What are the main features of innovative health systems reforms? 2. How have these reforms affected the health systems? 3. Are there lessons and other implications from these reforms? A common conceptual framework to compare health systems reforms is adopted, using a standardised format to report data of national health systems. A classification of health systems is constructed by categorising them according to the level of development of their respective economies: 1) Developed 2 )High Performing 3) Newly Industrialising 4) Transitional, and 5) Developing. A typology of common issues, challenges and responses are generalised for these health systems at different stages of socio-economic development of individual countries. Evaluative criteria are proposed to compare the long-term effects of these reforms on national health systems in terms of efficiency, equity, quality and sustainability.

Asia, Southeastern↗
PubMed2005

The Asia Pacific Academic Consortium for Public Heath (APACPH) the first ten years, from 1984 to 1994.

In January of 1984, five deans of schools of public health from Asia and the Pacific came together on the island of Kauai in Hawaii to formally establish the Consortium. The Consortium owes its cohesive strength through those first ten years of operation, to the dedicated faculty members in the fields of public health and community medicine whose overarching desire has been to seek representation of academic public health in the health decision making process affecting the positive promotion of health. By 1994 the Consortium found itself recognized on a world wide basis in the field of global health with what was described as having: "A great potential for extending the effectiveness of community and public health". "The author, a founding Dean feels that the Consortium's commitment is to shape rather than to await the future of health status improvement for the citizens of the Asia-Pacific region.

Asia↗