Safety assessment of a proprietary fermented soybean solution, Symbiota®, as an ingredient for use in foods and dietary supplements: Non-clinical studies and a randomized trial.

A safety evaluation was performed of Symbiota®, which is made by a proprietary anaerobic fermentation process of soybean with multistrains of probiotics and a yeast. The battery of genotoxicity studies showed that Symbiota® has no genotoxic effects. Safety and tolerability were further assessed by acute or repeated dose 28- and 90-day rodent studies, and no alterations in clinical observations, ophthalmological examination, blood chemistry, urinalysis, or hematology were observed between the control group and the different dosing groups (1.5, 5, and 15 mL/kg/day). There were no adverse effects on specific tissues or organs in terms of weight and histopathology. Importantly, the Symbiota® treatment did not perturb hormones and other endocrine-related endpoints. Of note, the No-Observed-Adverse-Effect-Level was determined to be 15 mL/kg/day in rats. Moreover, a randomized, double-blind, placebo-controlled clinical trial was recently conducted with healthy volunteers who consumed 8 mL/day of placebo or Symbiota® for 8 weeks. Only mild adverse events were reported in both groups, and the blood chemistry and blood cell profiles were also similar between the two groups. In summary, this study concluded that the oral consumption of Symbiota® at 8 mL/day by the general population does not pose any human health concerns.

Longitudinal assessment of milestone development among internal medicine residents in Taiwan.

BACKGROUND/PURPOSE: The Accreditation Council for Graduate Medical Education (ACGME) milestones have been implemented in residency training worldwide. We investigated the development of individual competency in first-year residents (R1) and second-year postgraduate students (PGY2) who received internal medicine training in Taiwan. METHODS: A multicenter observational cohort study was conducted to evaluate the competency-based milestone evaluation designed by the Taiwan Society of Internal Medicine in 2019. The evaluation was based on the ACGME-accredited milestone ratings. Periodic evaluation of milestone achievements of R1 and PGY2, who entered the internal medicine residency training at six medical centers, was performed. Each resident was evaluated every 3 months. RESULTS: Among the 98 R1 enrolled in 2019, substantial improvement in sub-competencies, including skill in performing procedures (Patient Care 4), clinical knowledge (Medical Knowledge 1), knowledge of diagnostic testing and procedures (Medical Knowledge 2), and identify impact the cost of health care and practices cost-effective care (Systems Based Practice 3) during the two years of training. Among the 107 R1 and 46 PGY2 enrolled in 2020, no significant difference in baseline milestone ratings was observed. However, the milestone assessments of R1 in 2020 showed improvement in nearly all sub-competencies compared with the stationary status of PGY2 in 2020. CONCLUSION: We demonstrate the application of ACGME-based accredited milestone ratings to target the educational goals of internal medicine residency training in Taiwan. Differences in milestone ratings between different PGY training systems exist. The long-term impact of performance among different PGY training systems requires further investigation.

Impact of COVID-19 pandemic on fecal immunochemical test screening uptake and compliance to diagnostic colonoscopy.

BACKGROUND AND AIM: During this COVID-19 pandemic, Taiwan is one of the few countries where fecal immunochemical test and endoscopic activity for colorectal cancer screening keeps ongoing. We aimed to investigate how screening uptake and colonoscopy rate were affected in one of the biggest screening hubs in Northern Taiwan. METHODS: We conducted a prospective observational study tracing and analyzing the screening uptake and the trend of compliance to diagnostic colonoscopy in fecal immunochemical test-positive subjects in the National Taiwan University Hospital screening hub since the outbreak of COVID-19 and compared it with that of the corresponding periods in the past 3 years. Cancellation and rescheduling rates of colonoscopy and related reasons were also explored. RESULTS: Screening uptake during December 2019 to April 2020 was 88.8%, which was significantly lower than that in the corresponding period of the past 3 years (91.2-92.7%, P for trend < 0.0001). Colonoscopy rate in this period was 66.1%, which was also significantly lower than that in the past 3 years (70.2-77.5%, P for trend = 0.017). Rescheduling or cancellation rate was up to 10.9%, which was significantly higher than that in the past 3 years (P for trend = 0.023), and half of them was due to the fear of being infected. CONCLUSION: Fecal immunochemical test screening was significantly affected by COVID-19 pandemic. In order to resume the practice in COVID-19 era, screening organizers should consider various approaches to secure timely diagnosis of colorectal cancer.

Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus.

OBJECTIVE: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC). METHODS: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. RESULTS: Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori. CONCLUSION: Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

Planning mass eradication of Helicobacter pylori infection for indigenous Taiwanese peoples to reduce gastric cancer.

BACKGROUND AND AIM: The aim of this study is to identify gastric cancer burden in Indigenous Taiwanese peoples and conduct a project to evaluate how to reduce the disparities most effectively in Indigenous communities. METHODS: First, we quantified the health disparities in gastric cancer in Indigenous peoples using data from the cancer registries during the period of 2006-2014. Second, we identified parameters that might be associated with Helicobacter pylori infection or help identify a good eradication strategy. RESULTS: Gastric cancer incidence (24.4 vs 12.3 per 100 000 person-years) and mortality rates (15.8 vs 6.8 per 100 000 person-years) were higher in Indigenous than in non-Indigenous, with 2.19-fold (95% confidence interval [CI]: 2.06-2.33) and 2.47-fold (2.28-2.67) increased risk, respectively. In Indigenous communities, H. pylori infection was more prevalent in Indigenous than in non-Indigenous (59.4% vs 31.5%, P < 0.01). Regression analyses consistently showed that either the mountain or plain Indigenous had 1.89-fold (95% CI: 1.34-2.66) and 1.73-fold (95% CI: 1.24-2.41) increased risk for H. pylori infection, respectively, as compared with non-Indigenous, adjusting for other baseline characteristics. The high infection rates were similarly seen in young, middle-aged, and older adults. Program eradication rates using clarithromycin-based triple therapy were suboptimal (73.7%, 95% CI: 70.0-77.4%); the habits of smoking (1.70-fold, 95% CI: 1.01-2.39) and betel nut chewing (1.54-fold, 95% CI: 0.93-2.16) were associated with the higher risk of treatment failure. CONCLUSION: Gastric cancer burden is higher in Indigenous Taiwanese peoples than in their non-Indigenous counterparts. Eliminating the prevalent risk factor of H. pylori infection is a top priority to reduce this health disparity.

The Rise of Colorectal Cancer in Asia: Epidemiology, Screening, and Management.

PURPOSE OF REVIEW: Colorectal cancer (CRC) remains the third most commonly diagnosed cancer globally, and its incidence and mortality rates have been on the rise in Asia. In this paper, we summarize the recent trends and screening challenges of CRC in this region. RECENT FINDINGS: In 2018, Asia had the highest proportions of both incident (51.8%) and mortality (52.4%) CRC cases (all genders and ages) per 100,000 population in the world. In addition, there has been a rising trend of this disease across Asia with some regional geographic variations. This rise in CRC can be attributed to westernized dietary lifestyle, increasing population aging, smoking, physical inactivity, and other risk factors. In curbing the rising trend, Japan, South Korea, Singapore, and Taiwan have launched nationwide population-based screening programs. CRC screening across this region has been found to be effective and cost-effective compared with no screening at all. The emergence of new therapies has caused a reduction in case fatality; however, these new options have had a limited impact on cure rates and long-term survival due to the great disparity in treatment capacity/resources and screening infrastructures among Asian countries with different degrees of economic development. CRC is still rising in Asia, and implementation of screening is necessary for moderate- to high-incidence countries and construction of treatment capacity is the priority task in low-incidence and low-income countries. Unless countries in Asia implement CRC screening, the incidence and mortality rates of this disease will continue to rise especially with the rapidly rising population growth, economic development, westernized lifestyle, and increasing aging.

Personalized risk assessment for dynamic transition of gastric neoplasms.

BACKGROUND: To develop an individually-tailored dynamic risk assessment model following a multistep, multifactorial process of the Correa's gastric cancer model. METHODS: First, we estimated the state-to-state transition rates following Correa's five-step carcinogenic model and assessed the effect of risk factors, including Helicobacter pylori infection, history of upper gastrointestinal disease, lifestyle, and dietary habits, on the step-by-step transition rates using data from a high-risk population in Matsu Islands, Taiwan. Second, we incorporated information on the gastric cancer carcinogenesis affected by genomic risk factors (including inherited susceptibility and irreversible genomic changes) based on literature to generate a genetic and epigenetic risk assessment model by using a simulated cohort identical to the Matsu population. The combination of conventional and genomic risk factors enables us to develop the personalized transition risk scores and composite scores. RESULTS: The state-by-state transition rates per year were 0.0053, 0.7523, 0.1750, and 0.0121 per year from normal mucosa to chronic active gastritis, chronic active gastritis to atrophic gastritis, atrophic gastritis to intestinal metaplasia, and intestinal metaplasia to gastric cancer, respectively. Compared with the median risk group, the most risky decile had a 5.22-fold risk of developing gastric cancer, and the least risky decile around one-twelfth of the risk. The median 10-year risk for gastric cancer incidence was 0.77%. The median lifetime risk for gastric cancer incidence was 5.43%. By decile, the 10-year risk ranged from 0.06 to 4.04% and the lifetime risk ranged from 0.42 to 21.04%. CONCLUSIONS: We demonstrate how to develop a personalized dynamic risk assessment model with the underpinning of Correa's cascade to stratify the population according to their risk for progression to gastric cancer. Such a risk assessment model not only facilitates the development of an individually-tailored preventive strategy with treatment for H. pylori infection and endoscopic screening but also provides short-term and long-term indicators to evaluate the program effectiveness.

Vaccination coverage and associated factors for receipt of the 23-valent pneumococcal polysaccharide vaccine in Taiwan: A nation-wide community-based study.

Older adults, particularly those with chronic obstructive pulmonary disease, are advised to receive 23-valent pneumococcal polysaccharide vaccine (PPV23). However, the PPV23 vaccination rate in Taiwan and the determinants of receipt remain unclear.We analyzed the data of 1475 community-dwelling older adults aged ≥75 years who participated in the Healthy Aging Longitudinal Study in Taiwan. Each participant received assessments of PPV23 status, sociodemographic factors (age, sex, education level, marital status, living alone, and occupation), and health-related factors (chronic diseases, smoking status, alcohol intake, physical activities, cognitive status, and physical performance). PPV23 rate was defined as the number of participants who reported receiving free PPV23 divided by the total number of candidates for free PPV23. Multinomial logistic regression analysis was applied to investigate the sociodemographic and health-related determinants of PPV23 status.A PPV23 vaccination rate of 20.7% (305/1475) was observed. Participants who were female, current smokers, and had a low peak expiratory flow were associated with PPV23 nonreceipt (all P <.05). Of the participants who had a low peak expiratory flow, low education status, and physical inactivity were associated with PPV23 nonreceipt (all P <.05).The PPV23 vaccination rate among adults aged ≥75 years was low. Older adults who were women, current smokers, or who had a low PEF were less likely to receive the PPV23. These findings support continual efforts to improve the PPV23 coverage rate in vulnerable populations.

Determinants of influenza vaccination in older adults: A nationwide community-based study in Taiwan.

AIMS: Influenza vaccination (InVa) is an effective measure for preventing influenza infection, which is a major cause of morbidity and mortality in older adults. However, the determinants of InVa remain unclear. METHODS: The present study included 4756 adults aged 55 years and older who completed the baseline examination of the Healthy Aging Longitudinal Study in Taiwan. During the examination, each participant received assessments of InVa status. Comprehensive assessments of sociodemographic (age, sex, education level, marital status, living alone and occupation) and health-related factors (chronic diseases, smoking status, alcohol intake, physical activities, cognitive status and physical performance) were also carried out. The InVa rate was defined as the number of participants who reported receiving free InVa divided by the total number of candidates for free InVa. Multinomial logistic regression analysis was applied to investigate the sociodemographic and health-related determinants of InVa status. RESULTS: The coverage rate of InVa was 44.8% (2130/4756). Older age (adjusted odds ratio [OR; >75 years vs <65 years] 7.72, 95% CI 6.26-9.52), multiple chronic diseases (OR [≥2 vs 0)] 1.31, 95% CI 1.10-1.65) and physical activity (OR [yes vs no] 1.43, 95% CI 1.23-1.64) were positively associated with receiving InVa. A current smoking status (OR 0.67, 95% CI 0.55-0.82) was negatively associated with receiving InVa. CONCLUSIONS: Older adults who received InVa differed from non-receivers in multiple sociodemographic and health-related characteristics. These findings support continual efforts to improve the InVa coverage rate in vulnerable populations. Geriatr Gerontol Int 2017; 17: 2396-2402.

Revisit of field cancerization in squamous cell carcinoma of upper aerodigestive tract: better risk assessment with epigenetic markers.

We quantified field cancerization of squamous cell carcinoma in the upper aerodigestive tract with epigenetic markers and evaluated their performance for risk assessment. Methylation levels were analyzed by quantitative methylation-specific PCR of biopsied specimens from a training set of 255 patients and a validation set of 224 patients. We also measured traditional risk factors based on demographics, lifestyle, serology, genetic polymorphisms, and endoscopy. The methylation levels of four markers increased stepwise, with the lowest levels in normal esophageal mucosae from healthy subjects without carcinogen exposure, then normal mucosae from healthy subjects with carcinogen exposure, then normal mucosae from cancer patients, and the highest levels were in cancerous mucosae (P < 0.05). Cumulative exposure to alcohol increased methylation of homeobox A9 in normal mucosae (P < 0.01). Drinkers had higher methylation of ubiquitin carboxyl-terminal esterase L1 and metallothionein 1M (P < 0.05), and users of betel quid had higher methylation of homeobox A9 (P = 0.01). Smokers had increased methylation of all four markers (P < 0.05). Traditional risk factors allowed us to discriminate between patients with and without cancers with 74% sensitivity (95% CI: 67%-81%), 74% specificity (66%-82%), and 80% area under the curve (67%-91%); epigenetic markers in normal esophageal mucosa had values of 74% (69%-79%), 75% (67%-83%), and 83% (79%-87%); and both together had values of 82% (76%-88%), 81% (74%-88%), and 91% (88%-94%). Epigenetic markers done well in the validation set with 80% area under the curve (73%-85%). We concluded that epigenetics could improve the accuracies of risk assessment.

Socio-demographic and health-related factors associated with cognitive impairment in the elderly in Taiwan.

BACKGROUND: Cognitive impairment is an age-related condition as the rate of cognitive decline rapidly increases with aging. It is especially important to better understand factors involving in cognitive decline for the countries where the older population is growing rapidly. The aim of this study was to examine the association between socio-demographic and health-related factors and cognitive impairment in the elderly in Taiwan. METHODS: We analysed data from 2119 persons aged 65 years and over who participated in the 2005 National Health Interview Survey. Cognitive impairment was defined as having the score of the Mini Mental State Examination lower than 24. The χ2 test and multiple logistic regression models were used to evaluate the association between cognitive impairment and variables of socio-demography, chronic diseases, geriatric conditions, lifestyle, and dietary factors. RESULTS: The prevalence of cognitive impairment was 22.2%. Results of multivariate analysis indicated that low education, being single, low social support, lower lipid level, history of stroke, physical inactivity, non-coffee drinking and poor physical function were associated with a higher risk of cognitive impairment. CONCLUSION: Most of the characteristics in relation to cognitive impairment identified in our analysis are potentially modifiable. These results suggest that improving lifestyle behaviours such as regular exercise and increased social participation could help prevent or decrease the risk of cognitive impairment. Further investigations using longitudinal data are needed to clarify our findings.

A prospective evaluation of the feasibility of primary screening with unsedated colonoscopy.

BACKGROUND: Colonoscopy is the most effective screening tool for colorectal cancer. In Taiwan, colonoscopy is used much less than sigmoidoscopy for screening because sedation significantly increases the cost and is not readily available, and unsedated colonoscopy is considered to be poorly tolerated. However, unsedated colonoscopy has been shown to be well accepted and may improve the cost-effectiveness and access to colonoscopic screening. OBJECTIVES: To compare the feasibility of unsedated colonoscopy and sigmoidoscopy for primary screening and to analyze factors associated with acceptance of the procedures and need for sedation. DESIGN: Single center, prospective. SETTING: National Taiwan University Medical Center. POPULATION AND INTERVENTIONS: A consecutive series of 261 subjects without history of colonoscopy or sigmoidoscopy who underwent unsedated colonoscopy (n = 176) or sigmoidoscopy (n = 85) for primary screening. MAIN OUTCOME MEASUREMENTS: Pain scores, acceptance, and need for sedation. RESULTS: No significant differences in pain, acceptance, and need for sedation were found between the colonoscopy and sigmoidoscopy groups. Only 9.6% in the colonoscopy group and 10.1% in the sigmoidoscopy group considered sedation necessary. Multivariate analyses revealed that the examinee's sex and the endoscopist, but not the type of endoscopic examination, were associated with the severity of pain and need for sedation. LIMITATIONS: Nonrandomized study design. CONCLUSIONS: Unsedated colonoscopy for primary screening is well accepted in nine tenths of examinees who accept this option and is similar to sigmoidoscopy in pain, acceptance, and need for sedation. Primary screening with unsedated colonoscopy is feasible, as with sigmoidoscopy.

Is eradication of Helicobacter pylori the feasible way to prevent gastric cancer? New evidence and progress, but still a long way to go.

Epidemiological, animal and biological studies provide compelling evidence for the role of Helicobacter pylori infection in gastric carcinogenesis. The finding that H. pylori-induced chronic atrophic gastritis is the major cause of gastric cancer suggests that eradication of the bacterium may prevent this malignancy. Computer-simulation studies have confirmed the cost-effectiveness of eradication in high-risk subjects; however, unresolved issues complicate active testing for and treatment of H. pylori infection among asymptomatic carriers. Concerns include the enormous costs for developing countries to implement strategies, the inconclusiveness of data from randomized controlled studies, the potential induction of antimicrobial resistance, and the uncertain effect of eliminating this organism on the spectrum of modern disease. Although current evidence is insufficient to recommend universal testing and treatment, it is possible to identify highly susceptible individuals who are most likely to benefit from treatment. Novel biomarkers for predicting risk are under extensive investigation, including genetic, epigenetic and proteinomic factors. The emerging evidence suggests that treatment of H. pylori infection in asymptomatic carriers may decrease the burden of gastric cancer. However, confirmation of long-term benefits remains a long way off.

Screening for gastric cancer in Asia: current evidence and practice.

Gastric cancer is the second most common cause of death from cancer in Asia. Although surgery is the standard treatment for this disease, early detection and treatment is the only way to reduce mortality. This Review summarises the epidemiology of gastric cancer, and the evidence for, and current practices of, screening in Asia. Few Asian countries have implemented a national screening programme for gastric cancer; most have adopted opportunistic screening of high-risk individuals only. Although screening by endoscopy seems to be the most accurate method for detection of gastric cancer, the availability of endoscopic instruments and expertise for mass screening remains questionable--even in developed countries such as Japan. Therefore, barium studies or serum-pepsinogen testing are sometimes used as the initial screening tool in some countries, and patients with abnormal results are screened by endoscopy. Despite the strong link between infection with Helicobacter pylori and gastric cancer, more data are needed to define the role of its eradication in the prevention of gastric cancer in Asia. At present, there is a paucity of quality data from Asia to lend support for screening for gastric cancer.

Age and distal colonic findings determine the yield of advanced proximal neoplasia in Chinese patients with rectal bleeding.

BACKGROUND AND AIMS: Few data were available on the optimal diagnostic strategy for Chinese patients with hematochezia. We aimed to evaluate the impact of age and distal colonic findings on the yield of diagnostic strategies in young Chinese patients with hematochezia. METHODS: Consecutive outpatients aged less than 50 years were analyzed using a hypothesized mixed diagnostic strategy to determine the optimal cut-off age for the use of sigmoidoscopy and colonoscopy. The efficacy and cost of the diagnostic strategy and the number of colonoscopies needed to detect one advanced proximal neoplasm (APN) using different cut-off ages were assessed. RESULTS: In the hypothesized mixed diagnostic strategy for young patients, the sensitivities for the detection of APN were 100%, 92% and 75% if the cut-off ages were 30, 35 and 40 years, respectively. The cost needed to detect one APN would be $US 3155, $US 3179 and $US 3497 if the cut-off ages were 30, 35 and 40 years, respectively. Colonoscopy would be performed in 84%, 69% and 51% of patients if the cut-off ages were 30, 35 and 40 years, respectively. CONCLUSION: Colonoscopy should be considered for Chinese patients with rectal bleeding who are aged > or =35 years or those aged <35 years who have adenoma in the distal colon.

Cost-effectiveness analysis between primary and secondary preventive strategies for gastric cancer.

OBJECTIVE: The present study is done to assess the relative cost-effectiveness, optimal initial age, and interscreening interval between primary and secondary prevention strategies for gastric cancer. METHODS: Base-case estimates, including variables of natural history, efficacy of intervention, and relevant cost, were derived from two preventive programs targeting a high-risk population. Cost-effectiveness was compared between chemoprevention with (13)C urea breath testing followed by Helicobacter pylori (H. pylori) eradication and high-risk surveillance based on serum pepsinogen measurement and confirmed by endoscopy. The main outcome measure was cost per life-year gained with a 3% annual discount rate. RESULTS: The incremental cost-effectiveness ratio (ICER) for once-only chemoprevention at age 30 years versus no screening was U.S. $17,044 per life-year gained. Eradication of H. pylori at later age or with a periodic scheme yielded a less favorable result. Annual high-risk screening at age of 50 years versus no screening resulted in an ICER of U.S. $29,741 per life-year gained. The ICERs of surveillance did not substantially vary with different initial ages or interscreening intervals. Chemoprevention could be dominated by high-risk surveillance when the initial age was older than 44 years. Otherwise, chemoprevention was more cost-effective than high-risk surveillance, either at ceiling ratios of U.S. $15,762 or up to U.S. $50,000. The relative cost-effectiveness was most sensitive to the infection rate of H. pylori and proportion of early gastric cancer in all detectable cases. CONCLUSIONS: Early H. pylori eradication once in lifetime seems more cost-effective than surveillance strategy. However, the choice is still subject to the risk of infection, detectability of early gastric cancer, and timing of intervention.

A community-based study of Helicobacter pylori therapy using the strategy of test, treat, retest, and re-treat initial treatment failures.

BACKGROUND: Although eradication of Helicobacter pylori infection can decrease the risk of gastric cancer, the optimal regimen for treating the general population remains unclear. We report the eradication rate (intention-to-treat and per protocol) of a community-based H. pylori therapy using the strategy of test, treat, retest, and re-treat initial treatment failures. MATERIALS AND METHODS: In 2004, a total of 2658 residents were recruited for 13C-urea breath testing. Participants with positive results for infection received a standard 7-day triple therapy (esomeprazole 40 mg once daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily), and a 10-day re-treatment (esomeprazole 40 mg once daily, amoxicillin 1 g twice daily, and levofloxacin 500 mg once daily) if the follow-up tests remained positive. Both H. pylori status and side-effects were assessed 6 weeks after treatment. RESULTS: Among 886 valid reporters, eradication rates with initial therapy were 86.9% (95% confidence interval [CI]: 84.7-89.1%) and 88.7% (95%CI: 86.5-90.9%) by intention-to-treat and per protocol analysis, respectively. Re-treatment eradicated infection in 91.4% (95%CI: 86-96.8%) of 105 nonresponders. Adequate compliance was achieved in 798 (90.1%) of 886 subjects receiving the initial treatment and in all 105 re-treated subjects. Mild side-effects occurred in 24% of subjects. Overall intention-to-treat and per protocol eradication rates were 97.7% (95%CI: 96.7-98.7%) and 98.8% (95%CI: 98.5-99.3%), respectively, which were only affected by poor compliance (odds ratio, 3.3; 95%CI, 1.99-5.48; p < .0001). CONCLUSIONS: A comprehensive plan using drugs in which the resistance rate is low in a population combined with the strategy of test, treat, retest, and re-treat of needed can result in virtual eradication of H. pylori from a population. This provides a model for planning country- or region-wide eradication programs.