Epidemiology of Virus Infection and Human Cancer.

Seven viruses including the Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), Kaposi's sarcoma herpes virus (KSHV), human immunodeficiency virus, type-1 (HIV-1), human T cell lymphotrophic virus, type-1 (HTLV-1), and human papillomavirus (HPV) have been classified as Group 1 human carcinogens by the International Agency for Research on Cancer (IARC). The conclusions are based on the findings of epidemiological and mechanistic studies. EBV, HPV, HTLV-1, and KSHV are direct carcinogens; HBV and HCV are indirect carcinogens through chronic inflammation; and HIV-1 is an indirect carcinogen through immune suppression. Some viruses may cause more than one cancer, while some cancers may be caused by more than one virus. However, only a proportion of persons infected by these oncogenic viruses will develop specific cancers. A series of studies have been carried out to assess the viral, host, and environmental cofactors of EBV-associated nasopharyngeal carcinoma, HBV/HCV-associated hepatocellular carcinoma, and HPV-associated cervical carcinoma. Persistent infection, high viral load, and viral genotype are important risk predictors of these virus-caused cancers. Risk calculators incorporating host and viral risk predictors have been developed for the prediction of long-term risk of hepatocellular carcinoma, nasopharyngeal carcinoma and cervical cancer. These risk calculators are useful for the triage and clinical management of infected patients. Both clinical trials and national programs of immunization, antiviral therapy and screening have demonstrated a significant reduction in the incidence of cancers caused by HBV, HCV, and HPV. Future research on gene-gene and gene-environment interactions of oncogenic viruses and the human host using large-scale longitudinal studies with serial measurements of biosignatures are in urgent need.

The Postnatal Risk, Resuscitation Success Rate and Outcomes of Pediatric Sudden Death in Taiwan.

BACKGROUND: The epidemiology of pediatric potentially sudden death (SD) events and the rescue rate remain unclear. METHODS: We established a birth cohort (2000-2014) from a national database 2000-2015. RESULTS: Of 3,097,277 live births, we identified 3126 children (56.1% male) with potentially SD events, including 887 who were rescued. The cumulative risk of potentially SD events for each neonate was 0.30, 0.62, 0.91, 1.05, and 1.13 per 1000 by 2 months, 0, 5, 11 and 14 years of age, respectively. Overall, 28.3% of the children were rescued from SD events, with a higher rate in neonates (69.6%) but lower rate in postneonatal infants. A cardiac diagnosis was noted in 596 (19.1%) patients, including congenital heart disease (CHD) (388), cardiac arrest (151), cardiomyopathy (23), myocarditis (12), Kawasaki disease (7) and arrhythmia (36). Coexisting severe CHD and events in postneonatal infancy were associated with a lower chance of resuscitation, whereas events within 1 week of age had a higher chance of resuscitation. Anoxic brain damage was noted in 174 (19.7%) patients and late death occurred in 348 (39.3%) patients after being rescued from SD. Late death was more common in males, those with anoxic brain damage, those with coexisting severe CHD, and postneonatal infants. CONCLUSIONS: In this birth cohort study, the postnatal cumulative risk of potentially SD events was 1 in 885 newborns by 14 years of age. Postneonatal infants and those with coexisting severe CHD had the highest risk and worst outcomes.

Phthalate exposure and prostate cancer in a population-based nested case-control study.

BACKGROUND: Phthalic acid esters are established as endocrine disruptors. The study aimed to evaluate the association between urinary phthalate metabolites and prostate cancer occurrence. METHODS: The study was based on the Taiwan Community-Based Cancer Screening Program, which was set up in 1991-1992 and followed periodically. By 2010, 80 incident prostate cancer cases were identified in the 12,020 men. For each case, 2 controls were randomly selected, matched by age (±3 years), urine collection date (±3 months), and residential township. Frequently used phthalate metabolites from the urine samples were quantified by liquid chromatography/electrospray ionization tandem mass spectrometry. Logistic regression was conducted to assess the association between the exposure levels and prostate cancer occurrence. RESULTS: Exposure to di (2-ethylhexyl), butyl-benzyl and di-isobutyl phthalates (DEHP, BBzP, DiBP) was positively associated with prostate cancer in men with waist circumference (WC) ≥90 cm but not in the leans. Odds ratio for the DEHP metabolite summary score (upper tertile compared to the rest) and prostate cancer were 7.76 (95% CI = 1.95-30.9) for WC ≥ 90 cm. CONCLUSIONS: DEHP, BBzP, and DiBP exposure were associated with prostate cancer occurrence in abdominally obese men. The main limitation remains the lack of mechanistic experiments and comparable toxicological data.

Cumulative postnatal risk of pediatric sudden death and all-cause mortality in nationwide birth cohorts of Taiwan and the United States.

BACKGROUND: To investigate the cumulative postnatal risk of pediatric sudden death (SD) for each neonate and the temporal/regional differences which are still unclear. METHODS: We established a birth cohort (2000-2014) from our national database and obtained reference data about the United States (US) from the national website. RESULTS: Among 3,097,277 live births, we identified 1661 children with SD (56.8% male). The postnatal cumulative risk of SD was 0.35, 0.49, 0.56 and 0.59/1000 by age 0, 5, 11 and 14 years. Coexisting cardiac diagnosis was noted in 347 (20.9%) and non-cardiac diagnosis in 300 (18.1%) patients. Cumulative all-cause mortality was 5.3, 6.78, 7.63 and 8.06/1000 by age 0, 5, 11 and 14 years. Risks of SD and all-cause death decreased over birthyear. SD risk decreased particularly after the 2008 birthyear. Risks of SD and all-cause death were the highest in Eastern Taiwan, but SD/all-cause death ratio was high in Taipei metropolitan and Northern Taiwan. Cumulative risk of SD (0.54/1000 by age 14) and all-cause mortality (9.06/1000 by age 14) in the US decreased over time. African-Americans were at the highest risks of SD and all-cause mortality. However, American-Indians/Alaska-natives exhibited the highest SD/all-cause death ratio. CONCLUSION: This study provides the cumulative risk of SD (1 in 1694 newborns) by age 14 years. The time trend underlines the effect of medical advance and education on SD prevention. Distinct regional/ethnic differences in risks of SD and all-cause death in Taiwan and the US indicate the necessity of different strategies to diminish the disparity.

Incidence and Postnatal Profile of Fontan Patients by Adolescence from a Nationwide Birth Cohort.

BACKGROUND: Although the Fontan procedure is associated with a variety of long-term complications, it is the mainstay treatment for congenital heart disease with a functioning single ventricle. Data concerning the epidemiological profile are scarce. METHODS: We investigated the current epidemiological profile using a 2000-2008 nationwide birth cohort from a 2000-2014 database (1,967,991 live births), with complete postnatal data for at least 6 years. We identified 363 patients (2792 patient-years of follow-up) who had received the Fontan procedure, giving an incidence of 0.184/1000 live births. RESULTS: The overall Fontan surgical survival rate was 81.8%. In post-Fontan patients, the 10-year survival was 0.822 (±0.026). Causes of death included cardiac (43.8%), infection (20.8%), out-of-hospital death (16.7%), sudden death (8.3%), cerebral vascular accident (8.3%) and malignancy (2.1%). The risk of unexpected death (sudden death and out-of-hospital death) was 4.0%, or 0.55% per post-Fontan patient-year. Arrhythmias were common (12.1%). Supraventricular tachycardia was the most common type of arrhythmia, and occurred prior to the Fontan procedure in 22 patients, with a cumulative risk of 2.2%, 6.3%, and 11.6% by the age of 1, 5 and 10 years, respectively. Arrhythmia intervention was performed in 40.9% of those with arrhythmia, including electrophysiological studies/ablation in 12 and device therapy in 6 patients. CONCLUSIONS: In conclusion, the incidence of Fontan patients was 0.184/1000 live births. Their medical complexity included a high risk of supraventricular tachycardia and unexpected death by adolescence.

Postnatal Risk of Acquiring Kawasaki Disease: A Nationwide Birth Cohort Database Study.

OBJECTIVE: To investigate the postnatal risk of Kawasaki disease and coronary complications from a nationwide birth cohort in Taiwan, a country with the third-highest incidence of Kawasaki disease worldwide. STUDY DESIGN: We enrolled children born between 2000 and 2009 with complete postnatal medical care records for 2000-2014 in the Taiwan national database. RESULTS: Out of a total of 2 150 590 live births, we identified 6690 (62.6% boys) patients with Kawasaki disease. The onset was mostly (93.9%) within the first 5 years of life (median, 16 months; 38% during infancy), but was rare within the first 3 months of life. The overall cumulative incidence of Kawasaki disease by age 5 years was 2.78‰ (3.33‰ for boys and 2.17‰ for girls; P < .001) and exhibited an increasing trend with birth year (from 2.28‰ for 2000 to 3.67‰ for 2009). The incidence ratio was 1.535 in boys and 1.055 in each increasing year. Kawasaki disease recurred more often in younger patients (cumulative incidence, 2.3% in infants vs 1.7% in children aged 1-4 years). Coronary complications occurred in 16.2% of the patients, including 4 cases of acute myocardial infarction (3 occuring during the acute stage and 1 occurring 5 years later). The probability of a major cardiac event (infarction, undergoing percutaneous coronary intervention or coronary artery bypass grafting, or death) by adolescence was 1.9%. CONCLUSIONS: The postnatal risk of Kawasaki disease was 3‰-4‰ and increased with every birth year. Patients with Kawasaki disease are at substantial risk for a major cardiac events during childhood.

Optically driven full-angle sample rotation for tomographic imaging in digital holographic microscopy.

This study presents a novel tomographic imaging technique for living biomedical samples using an optically driven full-angle rotation scheme based on digital holographic microscopy, in which the three-dimensional refractive index distribution inside the sample can be measured and analyzed. To accomplish the full-angle sample rotation, two optical traps are driven by highly focused spots on the top and bottom of the sample. The rim image of the sample outside the focal depth at the different rotation angles and propagation distances can be corrected and compensated, respectively, via numerical focusing; therefore, tomographic imaging of the sample can be conducted. The proposed approach shows that an entire symmetric spectrum can be acquired for tomographic reconstruction without the missing apple core problem as in traditional sample-rotation schemes. The three-dimensional refractive index of living yeast in a fluid medium is measured and verified.

Contemporary Postnatal Incidence of Acquiring Acute Myocarditis by Age 15 Years and the Outcomes From a Nationwide Birth Cohort.

OBJECTIVES: Acute myocarditis can be lethal, but the incidence remains unclear because of its wide manifestation spectrum. We investigated the postnatal incidence of acute myocarditis and risk factors for morbidity and mortality. DESIGN: Retrospective derived birth cohort study. SETTING: Taiwan National Health Insurance Database for the period 2000-2014. PATIENTS: Children born between 2000 and 2009 with complete postnatal medical care data for at least 5 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From among 2,150,590 live births, we identified 965 patients (54.8% male) admitted with the diagnosis of acute myocarditis, accounting for an overall incidence of 0.45/1,000. The cumulative incidence rates were 0.19/1,000, 0.38/1,000, 0.42/1,000, and 0.48/1,000 by ages 1, 5, 10, and 15 years, respectively. Male predominance was noted in infants and school age children (age group 6-14 yr). Arrhythmias, including tachyarrhythmia (4.8%) and bradyarrhythmia (1.1%), occurred in 56 patients. Extracorporeal membrane oxygenation support was provided to 62 patients (6.4%) and additional left ventricular assist devices in six of them. The mortality at discharge was 6.3%. The presence of ventricular tachyarrhythmia, bradyarrhythmia, and an onset at school age (6-14 yr) were associated with increased odds for the need for extracorporeal membrane oxygenation, which was the only predictor for mortality at discharge (hazard ratio, 7.85; 95% CI, 3.74-9.29). In patients who survived the acute myocarditis, late mortality was relatively low (36/904 = 4.0%). The overall survival of children with acute myocarditis were 90.9%, 90.3%, and 89.8% by the intervals of 1, 5, and 10 years after the myocarditis, respectively. CONCLUSIONS: This birth cohort study determined the cumulative incidence of acute myocarditis for neonates by 15 years old to be one in 2,105. In an era of extracorporeal membrane oxygenation, the need of extracorporeal membrane oxygenation may reflect the severity of acute myocarditis and predict its outcome.

Risk of Respiratory Syncytial Virus Infection in Cyanotic Congenital Heart Disease in a Subtropical Area.

OBJECTIVE: To compare the risk of respiratory syncytial virus (RSV)-associated hospitalization and analyze the epidemiology of RSV infection in patients with cyanotic and acyanotic congenital heart disease (CHD), we analyzed the nationwide health insurance database from 2005-2010. STUDY DESIGN: This study included 1050 patients with cyanotic CHD and 7077 patients with acyanotic CHD. Patients with acyanotic CHD were further classified into hemodynamically significant (hs)-acyanotic and non-hs-acyanotic groups according to whether they underwent surgery or took at least 2 anticongestive medications. RESULTS: RSV-associated hospitalization was higher in the cyanotic group than in hs-acyanotic and non-hs-acyanotic groups both before 1 year of age (4.8% vs 2.1% vs 1.5%, P < .001) and between 1 and 2 years of age (0.9% vs 0.56% vs 0.14%, P = .003). The hospitalization duration, intensive care, ventilator support prevalence, hospitalization cost, and mortality rate were significantly higher in the cyanotic group than in the other 2 groups. Logistic regression revealed that cyanotic CHD was the most significant risk factor for the ventilator support and RSV-associated mortality. In both patients with cyanotic and acyanotic CHD, RSV-associated hospitalization rate was higher in patients aged younger than 1 year and in spring and autumn in Taiwan, a subtropical country. CONCLUSIONS: The results show that patients with cyanotic CHD have a higher risk of severe RSV infection than do those with acyanotic CHD. RSV prophylaxis is more important and may reduce costs more for patients with cyanotic CHD.

Ventricular Fibrillation in a General Population　- A National Database Study.

BACKGROUND: Ventricular fibrillation (VF) is a life-threatening disease that can be remedied by prompt defibrillation. However, data regarding such risk in a general population remain limited. This general population study was to explore the epidemiological profile of VF.Methods and Results:We investigated patients with VF younger than 60 years (average population, 19,725,031) using a national database spanning the period 2000-2010. We identified 3,971 (68.4% male) patients with VF (crude incidence rate: 1.83/100,000). Incidence rates were low in patients younger than 10 years and increased steadily after adolescence. Comorbidities were noted in 2,766 (69.7%) patients, with 2,431 (61%) having cardiac diseases. Over half of the adolescent and young adult patients did not have comorbidities. Among the 838 deaths (mortality rate 21.1%), approximately half (381/838, 45.5%) occurred after arrival at emergency services (ES). The proportion of deaths after arrival at ES relative to total deaths increased sharply to a peak in the 15-19-years age group and thereafter remained stationary. CONCLUSIONS: VF patients, with a male dominance, increased after adolescence and were likely to die at presentation to ES. Approximately half of young adults, with high mortality, did not have comorbidities, suggesting underdiagnosis of underlying primary electrical diseases and the need for implementing automated external defibrillator programs. (Circ J 2016; 80: 2310-2316).

Paradigm shift in the intervention for secundum atrial septal defect in an era of transcatheter closure: A national birth cohort study.

BACKGROUND: Secundum atrial septal defect (ASDII) is a common congenital heart defect, but the intervention, either transcatheter or surgical, needs are unclear. This study was to examine the paradigm shift in its intervention in an era of transcatheter closure. METHODS AND RESULTS: The study birth cohort 2000-2008 (2,070,145 live births) with complete postnatal medical data was derived from the national database (2000-2014) of Taiwan, a country with national health insurance and easily accessible high-standard medical care. We found 5,515 patients with simple ASDII (median follow-up 12.2 years, one-third diagnosed after age 6 years, incidence 2.66/1,000 live births). Excluding patients with coexisting ventricular septal defect, ASDII intervention was performed in 1,435 of 4,585 patients: transcatheter closure in 1,080 (23.6%) and surgery in 355 (7.8%). The interventional need is 0.69 per 1,000 live births: 0.52 per 1,000 for transcatheter closure and 0.17 per 1,000 for surgery. In the era of transcatheter closure (July 2004-December 2014), ASDII intervention increased to 3.56-fold, but the number of operations decreased to half. The freedom from intervention was lower, and the age at intervention was younger (freedom from intervention at age 6 years, 0.749 vs 0.805, P < .001). In patients born in the era of transcatheter closure, 19.5% (108/555) of the intervention was surgery. Atrioventricular block occurred in 1.12% of those patients after transcatheter closure and none after surgery (P = .149). CONCLUSIONS: In the era of catheter intervention, the interventional criteria for ASDII are less strict and one-third of the patients may receive intervention, mostly transcatheter closure, at the pediatric ages.

National database study of survival of pediatric congenital heart disease patients in Taiwan.

BACKGROUND/PURPOSE: The incidence of congenital heart disease (CHD) and severe CHD is 13.08 and 1.51/1000 live births, respectively, in Taiwan, which has had national health insurance since 1995 and child health indices similar to those in the US. This study sought to further elucidate the fatality of CHD patients and their survival from a national database. METHODS: From the national health insurance database 2000-2010, we retrieved data from CHD patients who were diagnosed at age <6 years. The survival status at discharge was ascertained for estimation of survival. RESULTS: In total, 18,843 pediatric CHD patients were identified. The overall prevalence of CHD was 1288 per 100 000 live-births. Severe CHD (tetralogy of Fallot (4.4%), transposition of the great arteries (1.6%) and double outlet right ventricle (1.1%)) accounted for 11.5% of all cases. The 1-month/5-year survival in simple and severe CHD was 99.1%/97.5% and 90.2%/76.4%, respectively (p < 0.0001). The Kaplan-Meier survival at 5 years of age was lowest for hypoplastic left heart syndrome (19.7%), followed by transposition of the great arteries (66.7%), double outlet right ventricle (69.0%), and common ventricle (66.0%). The 5-year survival of the birth cohort in the same study period was 99.3%. CONCLUSION: This national database study revealed that the survival of children with simple CHD was still slightly lower than that of the general population and the survival of severe CHD patients, though only accounting for one-tenth of CHD cases, remained unsatisfactory. Such survival profiles are similar to those from Western reports and warrant a refined and dedicated medical care program for children with CHD.

Severe bacterial infection in patients with heterotaxy syndrome.

OBJECTIVE: To determine the incidence of sepsis in patients with heterotaxy syndrome. STUDY DESIGN: From our institutional database, we identified patients with heterotaxy syndrome and other complex congenital heart disease (CHD) born between 2001 and 2011. Severe bacterial infection was defined as sepsis with positive culture result or infection with abscess formation. RESULTS: We enrolled 95 patients with heterotaxy syndrome (88 with right atrial isomerism and 7 with left atrial isomerism) and 142 patients with complex CHD. With 1026 person-years follow-up, the 5-year survival was 52% and 65.7% in heterotaxy and complex CHD groups, respectively (P = .239). Community-acquired severe bacterial infection occurred only in heterotaxy syndrome (13 episodes in 10 patients, 3 of whom had spleen noted at imaging study) with 2- and 5 years cumulative severe bacterial infection rate of 9.6% and 14.5%, respectively. The overall mortality rate of those with community-acquired severe bacterial infection was 31%. Pneumococcus and Citrobacter freundii were the most common pathogens. Nosocomial severe bacterial infection occurred in 33.3% of all patients and 12.5% of all procedures. The rates (0.59 and 0.52/100 hospitalization days in heterotaxy and complex CHD group) and the pathogens of nosocomial severe bacterial infection were similar between heterotaxy and complex CHD groups. CONCLUSIONS: Patients with heterotaxy syndrome are at high risk for community-acquired severe bacterial infection and also have high mortality rate whether the spleen is present or not. The risk of nosocomial severe bacterial infection seems similar to that of patients with other complex CHD.

Epidemiology of virus infection and human cancer.

The International Agency for Research on Cancer (IARC) has comprehensively assessed the human carcinogenicity of biological agents. Seven viruses including Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), Kaposi's sarcoma herpes virus (KSHV), human immunodeficiency virus, type-1 (HIV-1), human T cell lymphotrophic virus, type-1 (HTLV-1), and human papillomavirus (HPV) have been classified as Group 1 human carcinogens by IARC. The conclusions are based on the findings of epidemiological and mechanistic studies. EBV, HPV, HTLV-1, and KSHV are direct carcinogens; HBV and HCV are indirect carcinogens through chronic inflammation; HIV-1 is an indirect carcinogen through immune suppression. Some viruses may cause more than one cancer, while some cancers may be caused by more than one virus. However, only a proportion of persons infected by these oncogenic viruses will develop specific cancers. A series of studies have been carried out to assess the viral, host, and environmental cofactors of EBV-associated nasopharyngeal carcinoma, HBV/HCV-associated hepatocellular carcinoma, and HPV-associated cervical carcinoma. Persistent infection and high viral load are important risk predictors of these virus-caused cancers. Risk calculators incorporating host and viral factors have also been developed for the prediction of long-term risk of hepatocellular carcinoma. These risk calculators are useful for the triage and clinical management of infected patients. Both clinical trials and national programs of immunization or antiviral therapy have demonstrated a significant reduction in the incidence of cancers caused by HBV, HCV, and HPV. Future researches on gene-gene and gene-environment interaction of oncogenic viruses and human host are in urgent need.

Effectiveness of the Huddles in Improving the Patient Safety Attitudes Among Clinical Team Members.

BACKGROUND AND OBJECTIVES: Huddles among members of interdisciplinary medical teams involve short stand-up sessions and allow team members to focus on existing or emerging patient safety issues, thereby facilitating team communication. Hospital managers are able to recognize the current situation of the organization through patient safety attitudes, strengthen team members' awareness of patient safety, and improve the quality of health care. The purpose of this study was to determine the effects of huddles on improving team members' attitudes toward patient safety. METHODS: We used a quasi-experimental design and selected 2 adult wards with similar properties as the experimental and comparison groups by convenience sampling. Data collection was from December 1, 2021, to June 30, 2022, at a teaching hospital in central Taiwan. Team members of the ward performing huddles formed the experimental group, and they participated 2 times per week in 15-minute huddles from 8:15 to 8:30 am for a total of 4 weeks. The comparison group adopted the routine team care process. Both groups completed the Safety Attitudes Questionnaire during the pre- and post-tests of the study. RESULTS: The experimental group scored significantly higher in the post-test than in the pre-test in all aspects of safety attitudes, with the exception of stress recognition. These improved aspects were teamwork climate (76.47 ± 15.90 vs 83.29 ± 13.52, P < .001), safety climate (75.94 ± 16.14 vs 82.81 ± 13.74, P < .001), job satisfaction (74.34 ± 20.22 vs 84.40 ± 17.22, P <.001), perceptions of management (78.02 ± 19.99 vs 85.51 ± 15.97, P < .001), and working conditions (78.85 ± 17.87 vs 86.81 ± 14.74, P < .001). CONCLUSION: Through the huddles, clinical team members improved their understanding of different aspects of safety attitudes. Such a study provided ward units with real-time improvement and adjustment in terms of patient safety during their medical work processes with better patient safety.

Epidemiology of Kawasaki disease: prevalence from national database and future trends projection by system dynamics modeling.

OBJECTIVE: To update the epidemiologic trend in Kawasaki disease (KD) and develop models for projection. STUDY DESIGN: From our national databases 2000-2010 and previous studies, we obtained the epidemiologic data to develop and validate system dynamics models. Population model incorporated birth rate and mortality. KD model incorporated the population at risk, incidence, and risk of coronary complications. RESULTS: The average annual incidence in age group <5, 5-10, 10-15, and 15-20 years was 67.3, 5.75, 0.79, and 0.26 per 100,000. The KD population was 23,349 and the model estimated 20,254 patients with KD, and 25% of these patients received medical care or continued surveillance in 2010. Projection up to 2030 suggests an average of 725 new patients with KD annually and a KD population of 35,006 by 2030. In 2030, 1469 patients with KD will need medical care for coronary complications. Simulation on the model modified to US data is also effective and suggests an average of 6200 new patients annually and KD population of 161,776 by 2030, and 5664 patients will need coronary care in 2030. By 2030, there will be 1 per 700 people in Taiwan and 1 per 1600 in the US with a history of KD. CONCLUSION: Simulations on our system dynamics models tailored to any epidemiologic and outcome variables and any changes with medical advance can dynamically project the futures.

Intratypic variants of human papillomavirus type 16 and risk of cervical neoplasia in Taiwan.

The associations between variants of human papillomavirus (HPV) 16 and risk of cervical neoplasia have been reported, but nucleotide variations of HPV 16 in Asian populations and their association with cervical neoplasia have not been evaluated extensively. During 1991-1992, 11,923 women from seven townships in Taiwan were enrolled. The HPV DNA in cervical cells was detected and genotyped using EasyChip HPV blot. Nucleotide variations in the long control region (LCR), E6, and E7 genes were determined using DNA sequencing for 170 HPV 16-positive cervical samples. The Asian variant was the most prevalent variant (81.8%) of HPV 16 in Taiwan, and was also associated with increased prevalence of histologically confirmed cervical intraepithelial neoplasia grade 3 or worse, showing an age-adjusted odds ratio (exact confidence limits) of 10.70 (1.62-451.05; P = 0.0049) compared to the HPV 16 European variant. Similar significant associations with cervical intraepithelial neoplasia grade 3 or worse were also observed for distinct nucleotide substitutions, including T178A/G, A647G, A7730C/G, T7781C, G7842A, and C24T/G. These results demonstrate that non-European variants (non-E) of HPV 16, predominantly Asian variants, are associated with increased risk for severe cervical neoplasia, compared with European variants. Molecular mechanisms accounting for varied cervical neoplasia risk among different HPV 16 variants warrant further investigation.

Impacts of Huddle Intervention on the Patient Safety Culture of Medical Team Members in Medical Ward: One-Group Pretest-Posttest Design.

Objective: A huddle is a short, regular meetings to discuss existing or emerging patient safety issues. Hospital administrators can encourage healthcare staff to voluntarily examine the potential occurrence and severity of risks, thereby enhancing awareness of patient safety. The purpose of this study is to explore the effects of huddle intervention on patient safety culture among medical team members and related factors. Methods: We used a one-group pretest-posttest research design and convenience sampled 109 members of the general internal medicine ward team members from a medical center in central Taiwan. They participated 2 times per week in 15-min huddles from 08:15 to 08:30 in the morning, which lasted for a total of 4 weeks. The process was based on submitted ideas, approved ideas, research ideas and standardization, and data on the safety attitudes questionnaire (SAQ) were collected during the huddles' intervention pretest and posttest. Results: After the huddle intervention, we found significantly improved scores for safety attitude, teamwork climate (76.49±16.13 vs 83.26±13.39, p < 0.001), safety climate (75.07±16.07 vs 82.63±13.72, p < 0.001), job satisfaction (73.67±19.84 vs 83.39±17.21, p < 0.001), perceptions of management (77.87±19.99 vs 84.86±16.03, p < 0.001) and working conditions (78.96±18.16 vs 86.18±14.90, p < 0.001). Correlation analyses on the differences between pretest and posttest showed that age had a significant correlation with safety climate (r = 0.22, p = 0.022) and working conditions (r = 0.20, p = 0.035). The number of times to participate in a huddle had a significant correlation with teamwork climate (r = 0.33, p =<.001), safety climate (r = 0.30, p = 0.002), job satisfaction (r = 0.19, p = 0.043), and work conditions (r = 0.28, p = 0.003). Conclusion: Huddles improve clinical team members' understanding of different dimensions and relate factors of safety attitudes. Implementation of the huddles involved standardized process will help hospital administrators understand the steps to parallel expansion to other wards.

Associations of human leukocyte antigen class II genotypes with human papillomavirus 18 infection and cervical intraepithelial neoplasia risk.

BACKGROUND: Only a small proportion of women infected with human papillomavirus type 18 (HPV18) may progress to persistent infection and cervical neoplasia. This community-based cohort study aimed to assess associations with human leukocyte antigen (HLA) class II genotypes for natural infection of HPV18 and subsequent risk of cervical neoplasia. METHODS: Among 10,190 cytologically normal participants, 125 with HPV18 infection were identified by HPV blot kit. HPV18 viral load at study entry was examined by real-time polymerase chain reaction; persistent infection was defined as HPV18 infection at 2 consecutive examinations. RESULTS: There was a significant association between HLA-DRB1*0403 allele and high HPV18 viral load (>1000 copies in 50 ng of total DNA) at study entry (odds ratio [OR], 7.2; 95% confidence interval [CI], 2.0-25.2). After adjustment for age and viral load at study entry, haplotype HLA-DRB1*0405-DQA1*0301-DQB1*0302 was significantly associated with persistent HPV18 infection (OR, 13.3; 95% CI, 1.7-105.9). HLA-DRB1*0403 allele was also associated with a significantly increased risk of high-grade squamous intraepithelial lesion or cancer, showing a multivariate-adjusted hazard ratio (95% CI) of 18.1 (2.6-128.5). CONCLUSIONS: HLA-DRB1*0403 allele and HLA-DRB1*0405-DQA1*0301-DQB1*0302 haplotype may play important roles in determination of high viral load and persistent infection of HPV18 and subsequent cervical neoplasia risk.

Baseline human papillomavirus infection, high vaginal parity, and their interaction on cervical cancer risks after a follow-up of more than 10 years.

OBJECTIVES: Human papillomavirus (HPV) has been recognized as a major factor for cervical cancer causation. Other factors, relating to reproduction, are also important. This study aims to disentangle the roles of baseline HPV infection, high vaginal parity (defined as having ≥4 vaginal deliveries), and the interaction between the two in predicting cervical cancer risk. METHODS: The authors apply a newly developed causal-pie modeling technique to analyze a cohort of more than 10,000 women conducted in Taiwan with more than 10 years of follow-up. The rate ratios adjusted by age and menopausal status were further modeled by an additive Poisson regression with non-negative parameters. The index of causal-pie weight (CPW) was calculated to indicate the proportion of cervical cancer cases attributable to a particular class of causal pies. RESULTS: It was found that the CPWs are 36.3 % for baseline HPV infection, 35.6 % for baseline HPV infection and high vaginal parity, and 28.1 % for other factors. CONCLUSIONS: A causal-pie modeling based on a women cohort in Taiwan successfully disentangles the roles of virus factors and reproductive factors at study entry, independently or interactively, on subsequent cervical cancer risk.