Comparative Effectiveness of Intra-Articular Hyaluronic Acid and Corticosteroid Injections on the Time to Surgical Knee Procedures.

BACKGROUND: Use of intra-articular hyaluronic acid (HA) injections to manage knee osteoarthritis (OA) remains controversial because of weak and conflicting evidence. The objective was to evaluate the effectiveness of intra-articular HA injections for knee OA management. METHODS: A nested cohort of persons with knee OA seeing a specialist was created using a 10% random sample of LifeLink Plus claims (2010-2015) to compare the risk of composite (any) knee surgical interventions, total (TKA)/unicompartmental knee arthroplasty (UKA) and TKA only among HA users and 2 comparison groups: corticosteroid (CS) users and HA/CS nonusers. A high-dimensional propensity score (hdPS) was used to match HA users with CS users and with HA/CS nonusers on background covariates. The risk of surgical interventions among HA users relative to the comparison groups was assessed using Cox proportional hazard models. RESULTS: Among 13,849 patients, 797 were HA users, 5327 were CS users, and 7725 were HA/CS nonusers. After hdPS matching, the risk of composite surgical interventions did not differ between HA users and HA/CS nonusers (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.67-1.16) and CS users (HR, 0.89; 95% CI, 0.65-1.12). Seven of the 8 sensitivity analyses demonstrated no significant benefit among HA users compared to CS users and HA/CS nonusers. A sensitivity analysis that restricted the study cohort to those who ultimately have knee surgery showed a lower risk of surgery of HA (HR, 0.87; 95% CI, 0.79-0.95). CONCLUSION: There were no significant differences in the risk of surgical interventions among HA users compared to HA/CS nonusers and CS users after accounting for residual confounding using an hdPS.

Comparison of Low-, Moderate-, and High-Molecular-Weight Hyaluronic Acid Injections in Delaying Time to Knee Surgery.

BACKGROUND: We compared the effectiveness of low-molecular-weight (MW) hyaluronic acid (HA) injections (LMWHA), moderate-MW HA injections (MMWHA), and high-MW HA injections (HMWHA) for prevention or delay of knee surgery in patients with knee osteoarthritis. METHODS: An observational cohort study using LifeLink Plus claims (2006-2015) was used. The primary outcome measure of the study included all surgical interventions of the knee. The secondary outcome measures were the following: (1) unicompartmental knee arthroplasty or total knee arthroplasty and (2) total knee arthroplasty only. A high-dimensional propensity score (hdPS) using 1:1 matching was used to adjust for confounding. The likelihood of each outcome was assessed using Cox proportional hazard models. RESULTS: A cohort of 30,417 incident HA users with knee osteoarthritis met our inclusion-exclusion criteria. There was no difference in the likelihood of composite surgical events between LMWHA users (hazard ratio, 0.939; 95% confidence interval, 0.870-1.013) and MMWHA users (hazard ratio, 1.032; 95% confidence interval, 0.952-1.119) when compared with HMWHA users in a matched hdPS analysis. However, a significantly lower likelihood for all outcome measures was demonstrated in LMWHA and MMWHA users compared with HMWHA users when hdPS was not used. CONCLUSION: There was no significant difference in the likelihood of surgical interventions between LMWHA, MMWHA, and HMWHA users after accounting for empirically derived confounders.

Association between Helicobacter pylori and Barrett's esophagus: a case-control study.

OBJECTIVES: The estimated association between Helicobacter pylori and Barrett's esophagus (BE) has been heterogenous across previous studies. In this study, we aimed to examine the association between H. pylori and BE and to identify factors that may explain or modify this association. METHODS: We conducted a case-control study in which we used screening colonoscopy controls recruited from primary care clinics as our primary control group in order to minimize selection bias. All participants underwent an esophagogastroduodenoscopy with gastric mapping biopsies. We used logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the association between H. pylori and BE while controlling for confounders. RESULTS: We identified 218 cases and 439 controls. The overall OR for the association between H. pylori and BE after controlling for age and white race was 0.55 (95% CI: 0.35-0.84). We observed an even stronger inverse association (OR: 0.28; 95% CI: 0.15, 0.50) among participants with corpus atrophy or antisecretory drug use ≥ 1 time per week (factors thought to lower gastric acidity), and no inverse association in patients without these factors (OR: 1.32; 95% CI: 0.66, 2.63). CONCLUSIONS: The association between H. pylori and a decreased risk for BE appears to occur in patients with factors that would likely lower gastric acidity (corpus atrophy or taking antisecretory drugs at least once a week).

Waist-to-hip ratio, but not body mass index, is associated with an increased risk of Barrett's esophagus in white men.

BACKGROUND & AIMS: Abdominal obesity increases the risk of gastroesophageal reflux disease (GERD) and also might contribute to the development of Barrett's esophagus (BE), although results are inconsistent. We examined the effects of waist-to-hip ratio (WHR) and body mass index (BMI) on the risk of BE and investigated whether race, GERD symptoms, or hiatus hernia were involved. METHODS: We conducted a case-control study using data from eligible patients who underwent elective esophagogastroduodenoscopy; 237 patients had BE and the other 1021 patients served as endoscopy controls. We also analyzed data and tissue samples from enrolled patients who were eligible for screening colonoscopies at a primary care clinic (colonoscopy controls, n = 479). All patients underwent esophagogastroduodenoscopy, completed a survey, and had anthropometric measurements taken. WHR was categorized as high if it was 0.9 or greater for men or 0.85 or greater for women. Data were analyzed with logistic regression. RESULTS: There was no association between BMI and BE. However, more patients with BE had a high WHR (92.4%) than endoscopy controls (79.5%) or colonoscopy controls (84.6%) (P < .001 and P = .008, respectively). In adjusted analysis, patients with BE were 2-fold more likely to have a high WHR than endoscopy controls (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.1-3.5), this association was stronger for patients with long-segment BE (OR, 2.81; 95% CI, 1.0-7.9). A high WHR was associated significantly with BE only in whites (OR, 2.5; 95% CI, 1.2-5.4), but not in blacks or Hispanics. GERD symptoms, hiatus hernia, or gastroesophageal valve flap grade could not account for the association. CONCLUSIONS: High WHR, but not BMI, is associated with a significant increase in the risk of BE, especially long-segment BE and in whites. The association is not caused by GERD symptoms or hiatus hernia.

The association between Barrett's esophagus and Helicobacter pylori infection: a meta-analysis.

OBJECTIVE: The effect of Helicobacter pylori on Barrett's esophagus is poorly understood. We conducted a meta-analysis to summarize the existing literature examining the effect that H. pylori has on Barrett's esophagus. DESIGN: We performed a comprehensive search to identify studies pertaining to the association between H. pylori and Barrett's esophagus. We conducted meta-regression analyses to identify sources of variation in the effect of H. pylori on Barrett's esophagus. RESULTS: Our analysis included a total of 49 studies that examined the effect of H. pylori on Barrett's esophagus and seven studies that examined the effect of cag A positivity on Barrett's esophagus. Overall, H. pylori, and even more so cag A, tended to be protective for Barrett's esophagus in most studies; however, there was obvious heterogeneity across studies. The effect of H. pylori on Barrett's esophagus varied by geographic location and in the presence of selection and information biases. Only four studies were found without obvious selection and information bias, and these showed a protective effect of H. pylori on Barrett's esophagus (Relative risk = 0.46 [95% CI: 0.35, 0.60]). CONCLUSIONS: Estimates for the effect of H. pylori on Barrett's esophagus were heterogeneous across studies. We identified selection and information bias as potential sources of this heterogeneity. Few studies without obvious selection and information bias have been conducted to examine the effect of H. pylori on Barrett's esophagus, but in these, H. pylori infection is associated with a reduced risk of Barrett's esophagus.

State-wide random seroprevalence survey of SARS-CoV-2 past infection in a southern US State, 2020.

The purpose of this cross-sectional study was to estimate the proportion of Arkansas residents who were infected with the SARS-CoV-2 virus between May and December 2020 and to assess the determinants of infection. To estimate seroprevalence, a state-wide population-based random-digit dial sample of non-institutionalized adults in Arkansas was surveyed. Exposures were age, sex, race/ethnicity, education, occupation, contact with infected persons, comorbidities, height, and weight. The outcome was past COVID-19 infection measured by serum antibody test. We found a prevalence of 15.1% (95% CI: 11.1%, 20.2%) by December 2020. Seropositivity was significantly elevated among participants who were non-Hispanic Black, Hispanic (prevalence ratio [PRs]:1.4 [95% CI: 0.8, 2.4] and 2.3 [95% CI: 1.3, 4.0], respectively), worked in high-demand essential services (PR: 2.5 [95% CI: 1.5, 4.1]), did not have a college degree (PR: 1.6 [95% CI: 1.0, 2.4]), had an infected household or extra-household contact (PRs: 4.7 [95% CI: 2.1, 10.1] and 2.6 [95% CI: 1.2, 5.7], respectively), and were contacted in November or December (PR: 3.6 [95% CI: 1.9, 6.9]). Our results indicate that by December 2020, one out six persons in Arkansas had a past SARS-CoV-2 infection.

Double-blind randomized trial of quadruple sequential Helicobacter pylori eradication therapy in asymptomatic infected children in El Paso, Texas.

OBJECTIVES: We assessed the efficacy of a novel quadruple sequential 10-day eradication therapy, its compliance, and reported adverse events in a sample of asymptomatically Helicobacter pylori-infected children in El Paso, Texas, as part of a study aiming to assess the influence of this infection on the levels of markers of iron stores. PATIENTS AND METHODS: Using a double-blind randomized trial design, 110 asymptomatic children ages 3 to 11 with H pylori infection were randomly assigned to receive either a 10-day course of sequential eradication therapy plus 6 weeks of iron supplementation, eradication therapy plus placebo, iron supplementation plus placebo, or placebo only. H pylori infection status was assessed ≥45 days after treatment using the urea breath test. Analyses compared the proportion of subjects cured according to assignment to and completion of the sequential eradication therapy. RESULTS: Intent-to-treat and per-protocol analyses indicated that 44.3% and 52.9%, respectively, of the children receiving the novel quadruple sequential therapy had their infection eradicated compared with 12.2% and 15.4% in the arms receiving iron or placebo only, respectively (P < 0.001 in both analyses). Study medications were taken with no or only mild adverse events in most children. CONCLUSIONS: A quadruple sequential regimen eradicated H pylori in only half the asymptomatic children receiving this treatment. There was no difference in the cure rates of those receiving iron supplementation and those receiving placebo.

Exposure to Helicobacter pylori-positive siblings and persistence of Helicobacter pylori infection in early childhood.

OBJECTIVES: Cross-sectional studies suggest that Helicobacter pylori may be transmitted between siblings. The present study aimed to estimate the effect of an H pylori-infected sibling on the establishment of a persistent H pylori infection. MATERIALS AND METHODS: The authors used data collected from a Texas-Mexico border population from 1998 to 2005 (the "Pasitos Cohort Study"). Starting at age 6 months, H pylori and factors thought to be associated with H pylori were ascertained every 6 months for participants and their younger siblings. Hazard ratios were estimated from proportional hazards regression models with household-dependent modeling. RESULTS: Persistent H pylori infection in older siblings always preceded persistent infection in younger siblings. After controlling for mother's H pylori status, breast-feeding, antibiotic use, and socioeconomic factors, a strong effect was estimated for persistent H pylori infection in an older sibling on persistent infection in a younger sibling (hazard ratio 7.6, 95% confidence interval 1.6-37], especially when the difference in the age of the siblings was less than or equal to 3 years (hazard ratio 16, 95% confidence interval 2.5-112). CONCLUSIONS: These results suggest that when siblings are close in age, the older sibling may be an important source of H pylori transmission for younger siblings.

Antibiotics taken for other illnesses and spontaneous clearance of Helicobacter pylori infection in children.

PURPOSE: Factors that determine persistence of untreated Helicobacter pylori (H. pylori) infection in childhood are not well understood. We estimated risk differences for the effect of incidental antibiotic exposure on the probability of a detected clearance at the next test after an initial detected H. pylori infection. METHODS: The Pasitos Cohort Study (1998-2005) investigated predictors of H. pylori infection in children from El Paso, Texas, and Juarez, Mexico. Children were screened for infection at 6-month target intervals from 6 to 84 months of age, using the 13C-urea breath test corrected for body-size-dependent variation in CO2 production. Exposure was defined as courses of any systemic antibiotic (systemic) or those with anti-H. pylori action (HP-effective) reported for the interval between initial detected infection and next test. Binomial regression models included country of residence, mother's education, adequacy of prenatal care, age at infection, and interval between tests. RESULTS: Of 205 children with a test result and antibiotic data following a detected infection, the number of children who took > or =1 course in the interval between tests was 74 for systemic and 33 for HP-effective. The proportion testing negative at the next test was 66% for 0 courses, 72% for > or =1 systemic course, and 79% for > or =1 HP-effective course. Adjusted risk differences (95%CI) for apparent clearance, comparing > or =1 to 0 courses were 10% (1-20%) for systemic and 11% (0-21%) for HP-effective. CONCLUSIONS: Incidental antibiotic exposure appears to influence the duration of childhood H. pylori infection but seems to explain only a small portion of spontaneous clearance.

The use of electronic nicotine delivery systems during pregnancy and the reproductive outcomes: A systematic review of the literature.

INTRODUCTION: Use of electronic nicotine delivery systems (ENDS) among pregnant women is of great concern. To our knowledge the current literature provides conflicting views regarding the uncertainties of the effects of ENDS use during pregnancy on the health of the fetus. METHODS: We searched PubMed, CINAHL, and EMBASE, for the period 2007 to October 2017 for terms to identify publications on ENDS use during pregnancy and the reproductive outcomes. We updated the search for the period November 2017 to November 2018 using Ovid Medline. We obtained full text of articles and present a summary of the contents. RESULTS: We found no studies of pregnant women exposed to ENDS use and its effect on their fetus or neonates. However, there is a growing body of experimental studies in animals that suggest that nicotine in ENDS alters DNA methylation, induces birth defects, reduces the birth weight, and affects the development of the heart and lungs of their offspring. A large population-based cohort study in the United States estimated that 5% of pregnant women were current ENDS users in 2014; most of them also smoked cigarettes. Surveys conducted among practitioners indicate that there is a need to screen and counsel pregnant women. Systematic reviews and meta-analysis of studies of women who used smokeless tobacco during pregnancy suggest that prenatal nicotine alone is a risk factor for low birth weight, premature delivery, and stillbirth. CONCLUSIONS: There were no previous studies assessing the reproductive effects of ENDS use during pregnancy. However, prenatal exposure to nicotine is known to be harmful to the fetus and the pregnancy.

Using Machine Learning to Predict Progression in the Gastric Precancerous Process in a Population from a Developing Country Who Underwent a Gastroscopy for Dyspeptic Symptoms.

BACKGROUND: Gastric cancer is the fourth most common cancer and the third most common cause of cancer deaths worldwide. Morbidity and mortality from gastric cancer may be decreased by identification of those that are at high risk for progression in the gastric precancerous process so that they can be monitored over time for early detection and implementation of preventive strategies. METHOD: Using machine learning, we developed prediction models for gastric precancerous progression in a population from a developing country with a high rate of gastric cancer who underwent gastroscopies for dyspeptic symptoms. In the data imputed for completeness, we divided the data into a training and a validation test set. Using the training set, we used the random forest method to rank potential predictors based on their predictive importance. Using predictors identified by the random forest method, we conducted best subset linear regressions with the leave-one-out cross-validation approach to select predictors for overall progression and progression to dysplasia or cancer. We validated the models in the test set using leave-one-out cross-validation. RESULTS: We observed for all models that complete intestinal metaplasia and incomplete intestinal metaplasia were the strongest predictors for further progression in the precancerous process. We also observed that a diagnosis of no gastritis, superficial gastritis, or antral diffuse gastritis at baseline was a predictor of no progression in the gastric precancerous process. The sensitivities and specificities were 86% and 79% for the general model and 100% and 82% for the location-specific model, respectively. CONCLUSION: We developed prediction models to identify gastroscopy patients that are more likely to progress in the gastric precancerous process, among whom routine follow-up gastroscopies can be targeted to prevent gastric cancer. Future external validation is needed.

The Association between Salt and Potential Mediators of the Gastric Precancerous Process.

BACKGROUND: The process by which salt affects the gastric precancerous process has not been adequately studied in humans. METHODS: We investigated the effects of salt on gastric inflammation, epithelial damage, the density of Helicobacter pylori infection, and gastric epithelial cell proliferation, all of which may be mediators between salt and gastric precancerous/cancerous lesions. These potential mediators were measured using gastric biopsies as: (a) the density of polymorphonuclear and mononuclear cells (gastric inflammation), (b) mucus depletion (gastric epithelial damage), and (c) the severity of H. pylori infection. Salt intake was measured with spot urine samples (using urinary sodium/creatinine ratios), self-reported frequency of adding salt to food, and as total added salt. RESULTS: The average sodium/creatinine ratio (at baseline and post-treatment at five months) was associated with increased epithelial damage over the 12-year follow-up period among those with a greater severity of chronic inflammation and among those with continued H. pylori infection after treatment at five months. This association was stronger when both severe gastric inflammation and H. pylori infection were present at five months (ß: 1.112, 95% CI: 0.377, 1.848). CONCLUSION: In humans, salt was associated with an increase in epithelial damage in stomachs with more severe previous H. pylori-induced chronic inflammation.

Association between Dietary Salt Intake and Progression in the Gastric Precancerous Process.

Gastric cancer is the third leading cause of cancer mortality worldwide. Studies investigating the effect of salt on gastric cancer have mainly used self-reported measures, which are not as accurate as sodium/creatinine ratios because individuals may not know the amount of salt in their food. Using data from a prospective cohort study, we investigated the effect of salt intake on progression to gastric precancerous lesions. Salt intake was estimated by urinary sodium/creatinine ratios, self-reported frequencies of adding salt to food, and total added table salt. We repeated the analyses among groups with and without Helicobacter pylori infection. We did not observe a positive association between salt intake, measured by urinary sodium/creatinine ratio, and overall progression in the gastric precancerous process (adjusted risk ratio (RR): 0.94; 95% confidence interval (CI) 0.76-1.15). We did observe an association between salt intake and increased risk for progression to dysplasia or gastric cancer overall (adjusted risk ratio (RR): 1.32; 95% confidence interval (CI): 0.96-1.81), especially among those who continued to have H. pylori infection at the five-month follow-up (adjusted RR: 1.53; 95% CI: 1.12-2.09), and among those who had persistent H. pylori infection over 12 years (adjusted RR: 1.49; 95% CI: 1.09-2.05). Salt intake may increase the risk of gastric dysplasia or gastric cancer in individuals with H. pylori infection.

Use of Electronic Nicotine Delivery Systems (ENDS) by pregnant women I: Risk of small-for-gestational-age birth.

INTRODUCTION: The 2016 US Surgeon General's Report suggests that the use of electronic nicotine delivery systems (ENDS) is a fetal risk factor. However, no previous study has estimated their effect on adverse pregnancy outcomes. We assessed the prevalence of current ENDS use in pregnant women and explored the effect on birth weight and smallness-for-gestational-age (SGA), correcting for misclassification from nondisclosure of smoking status. METHODS: We conducted a cohort study with 248 pregnant women using questionnaire data and biomarkers (salivary cotinine, exhaled carbon monoxide, and hair nicotine). We evaluated the association between birth weight and the risk of SGA by applying multivariate linear and log-binomial regression to reproductive outcome data for 232 participants. Participants who did not disclose their smoking status were excluded from the referent group. Sensitivity analysis corrected for misclassification of smoking/ENDS use status. RESULTS: The prevalence of current ENDS use among pregnant women was 6.8% (95% CI: 4.4-10.2%); most of these (75%) were concurrent smokers. Using self-reports, the estimated risk ratio of SGA for ENDS users was nearly two times the risk in the unexposed (RR=1.9, 95% CI: 0.6-5.5), and over three times that for ENDS-only users versus the unexposed (RR=3.1, 95% CI: 0.8-11.7). Excluding from the referent group smokers who did not disclose their smoking status, the risk of SGA for ENDS-only use was 5 times the risk in the unexposed (RR=5.1, 95% CI: 1.1- 22.2), and almost four times for all types of ENDS users (RR=3.8, 95% CI: 1.3-11.2). SGA risk ratios for ENDS users, corrected for misclassification due to self-report, were 6.5-8.5 times that of the unexposed. CONCLUSIONS: Our data suggest that ENDS use is associated with an increased risk of SGA.

Use of electronic nicotine delivery systems by pregnant women II: Hair biomarkers for exposures to nicotine and tobacco-specific nitrosamines.

INTRODUCTION: Public awareness of electronic nicotine delivery systems (ENDS) has increased over time, and the perception that ENDS offer a safer alternative to cigarettes may lead some pregnant women to use them to reduce cigarette smoking during pregnancy. No previous studies have used metabolite levels in hair to measure nicotine exposure for ENDS users during pregnancy. We aimed to measure and compare levels of nicotine, cotinine, and tobacco-specific nitrosamines (TSNAs) in hair samples from pregnant women who were current ENDS users, current smokers, and current non-smokers. We also aimed to estimate the association between ENDS use/smoking and smallness for gestational age (SGA). METHODS: We used hair specimens from pregnant women who were dual users (ENDS and cigarettes), smokers, and non-smokers from a prospective cohort study to estimate exposure to nicotine, cotinine, and TSNAs. The exposure biomarkers and self-reports of smoking and ENDS use were used in log-binomial regression models to estimate risk ratios (RRs) for SGA among offspring. RESULTS: Nicotine concentrations for pregnant dual users were not significantly different from those for smokers (11.0 and 10.6 ng/mg hair, respectively; p=0.58). Similarly, levels of cotinine, and TSNAs for pregnant dual users were not lower than those for smokers. The RR for SGA was similar for dual users and smokers relative to nonsmokers, (RR=3.5, 95% CI: 0.8-14.8) and (RR=3.3, 95% CI: 0.9-11.6), respectively. Using self-reports confirmed by hair nicotine, the RR values for dual ENDS users and smokers were 8.3 (95% CI: 1.0-69.1) and 7.3 (95% CI:1.0-59.0), respectively. CONCLUSIONS: We did not observe lower levels of nicotine, cotinine, and TSNAs for current dual users compared to smokers during pregnancy. The risk of SGA for offspring of pregnant dual users was similar to that for offspring of pregnant smokers. Future studies are needed to further estimate the magnitude of the association between ENDS use and smallness for gestational age.

Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial.

The Nutritional Prevention of Cancer Trial was a randomized, clinical trial designed to evaluate the efficacy of selenium as selenized yeast (200 microg daily) in preventing the recurrence of nonmelanoma skin cancer among 1312 residents of the Eastern United States. Original secondary analyses through December 31, 1993 showed striking inverse associations between treatment and the incidence of total [hazard ratio (HR) = 0.61, 95% confidence interval (CI) = 0.46-0.82], lung, prostate, and colorectal cancer and total cancer mortality. This report presents results through February 1, 1996, the end of blinded treatment. Effect modification by baseline characteristics is also evaluated. The effects of treatment overall and within subgroups of baseline age, gender, smoking status, and plasma selenium were examined using incidence rate ratios and Cox proportional hazards models. Selenium supplementation reduced total (HR = 0.75, 95% CI = 0.58-0.97) and prostate (HR = 0.48, 95% CI = 0.28-0.80) cancer incidence but was not significantly associated with lung (HR = 0.74, 95% CI = 0.44-1.24) and colorectal (HR = 0.46, 95% CI = 0.21-1.02) cancer incidence. The effects of treatment on other site-specific cancers are also described. The protective effect of selenium was confined to males (HR = 0.67, 95% CI = 0.50-0.89) and was most pronounced in former smokers. Participants with baseline plasma selenium concentrations in the lowest two tertiles (<121.6 ng/ml) experienced reductions in total cancer incidence, whereas those in the highest tertile showed an elevated incidence (HR = 1.20, 95% CI = 0.77-1.86). The Nutritional Prevention of Cancer trial continues to show a protective effect of selenium on cancer incidence, although not all site-specific cancers exhibited a reduction in incidence. This treatment effect was restricted to males and to those with lower baseline plasma selenium concentrations.

Sources of variation of Helicobacter pylori treatment success in adults worldwide: a meta-analysis.

BACKGROUND: A vast number of Helicobacter pylori treatment trials have been conducted. Regimens may vary in efficacy in different patient populations. METHODS: We identified sources of treatment effect variation from 618 treatment groups using weighted cross-classified multi-level meta-regression models. Summary effect estimates were calculated within groups that lacked identified heterogeneity. RESULTS: Overall, treatment was less successful with shorter treatment duration and dual drug (versus triple or quadruple drug) therapies. For nitroimidazole-based regimens, treatment was less successful in populations with frequent childhood H. pylori infection or metronidazole resistance and more successful in northeastern Asia. Non-nitroimidazole treatments of longer duration and those from less recent reports were most successful. Some one-week regimens--(nitroimidazole/ tetracycline/bismuth, ranitidine bismuth citrate/amoxicillin/clarithromycin, and clarithromycin/amoxicillin/proton pump inhibitor) were highly successful in northeastern Asia regardless of metronidazole resistance. The most successful regimen in populations with both a high prevalence of metrondiazole resistance and frequent infection in children (metronidazole/furazolidone/amoxicillin) eliminated fewer than 70% of infections. CONCLUSIONS: More effective treatments are needed for most populations of the world where H. pylori infection in children and drug resistance are common. Current treatment guidelines do not coincide with the best treatment regimens identified in this meta-analysis.