Tocilizumab Is Associated with Increased Risk of Fungal Infections among Critically Ill Patients with COVID-19 and Acute Renal Failure: An Observational Cohort Study.

RESEARCH QUESTION: Does treatment with tocilizumab increase the risk of a fungal infection in critically ill patients with coronavirus-19? BACKGROUND: Numerous therapies have been evaluated as possible treatments for coronavirus-2019 caused by severe acute respiratory syndrome coronavirus-2. Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 receptor that has found a role as a therapy for patients with severe coronavirus-19 pneumonia. The immunomodulatory effects of tocilizumab may have the unintended consequence of predisposing recipients to secondary infections. We sought to assess the risk of invasive fungal disease and the therapeutic impact of tocilizumab on the hospital length of stay, duration of mechanical ventilation, and intensive-care-unit length of stay in critically ill patients with severe coronavirus-19 pneumonia. METHODS: Records of critically ill patients with coronavirus-2019 admitted from March to September 2020 at our institution were reviewed. The risk for fungal infections, intensive-care-unit length of stay, hospital length of stay, and duration of mechanical ventilation in those that received tocilizumab in addition to standard coronavirus-2019 treatments was assessed. RESULTS: Fifty-six critically ill patients treated with dexamethasone and remdesivir for coronavirus-2019 were included, of which 16 patients also received tocilizumab. The majority of the cohort was African American, Asian, or of other ethnic minorities (53.6%). Invasive fungal infections occurred in 10.7% of all patients, and infection rates were significantly higher in the tocilizumab group than in the control group (31.2% vs. 2.5%, risk difference [RD] = 28.8%, p < 0.01). The increased risk in the tocilizumab group was strongly associated with renal replacement therapy. There was a dose-response relationship between the risk of fungal infection and number of tocilizumab doses received, with 2.5% of infections occurring with zero doses, 20% with a single dose (RD = 17.5%), and 50% with two doses (RD = 47.5%) (trend test p < 0.001). In addition, ICU LOS (23.4 days vs. 9.0 days, p < 0.01), the duration of mechanical ventilation (18.9 vs. 3.5 days, p = 0.01), and hospital length of stay (LOS) (29.1 vs. 15.5, p < 0.01) were increased in patients that received tocilizumab. CONCLUSIONS: Repurposed immunomodulator therapies, such as tocilizumab, are now recommended treatments for severe coronavirus-2019 pneumonia, but safety concerns remain. In this early pandemic cohort, the addition of tocilizumab to dexamethasone was associated with an increased risk of fungal infection in those that were critically ill and received renal replacement therapy. Tocilizumab use was also associated with increased ICU and hospital LOSs and duration of mechanical ventilation.

Temporal Variations in Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Infections by Race and Ethnicity in Arkansas.

Background: The aim of this study was to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates in the small rural state of Arkansas, using SARS-CoV-2 antibody prevalence as an indicator of infection. Methods: We collected residual serum samples from adult outpatients seen at hospitals or clinics in Arkansas for non-coronavirus disease 2019 (COVID-19)-related reasons. A total of 5804 samples were identified over 3 time periods: 15 August-5 September 2020 (time period 1), 12 September-24 October 2020 (time period 2), and 7 November-19 December 2020 (time period 3). Results: The age-, sex-, race-, and ethnicity-standardized SARS-CoV-2 seroprevalence during each period, from 2.6% in time period 1 to 4.1% in time period 2 and 7.4% in time period 3. No statistically significant difference in seroprevalence was found based on age, sex, or residence (urban vs rural). However, we found higher seroprevalence rates in each time period for Hispanics (17.6%, 20.6%, and 23.4%, respectively) and non-Hispanic Blacks (4.8%, 5.4%, and 8.9%, respectively) relative to non-Hispanic Whites (1.1%, 2.6%, and 5.5%, respectively). Conclusions: Our data imply that the number of Arkansas residents infected with SARS-CoV-2 rose steadily from 2.6% in August to 7.4% in December 2020. There was no statistical difference in seroprevalence between rural and urban locales. Hispanics and Blacks had higher rates of SARS-CoV-2 antibodies than Whites, indicating that SARS-CoV-2 spread disproportionately in racial and ethnic minorities during the first year of the COVID-19 pandemic.

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.

Bacillus of Calmette and Guérin (BCG) and the risk of leprosy in Ciudad del Este, Paraguay, 2016-2017.

OBJECTIVES: Paraguay has experienced a 35% reduction in the detected incidence of leprosy during the last ten years, as the vaccination coverage against tuberculosis (Bacillus of Calmette and Guérin [BCG] vaccine) reached ≥95% among infants. The objective of this case-control study was to evaluate the protective effect of BCG on the risk of leprosy. METHODS: We used a population-based case-control study of 20 leprosy confirmed cases reported among residents of Ciudad del Este, Paraguay, diagnosed in 2016-2017. Three controls were selected from a random sample of households from the city. We assessed vaccine effectiveness using 1- odds ratio [OR], and confounding for age, gender, education, occupation, and marital status using stratified and exact logistic regression, and explored if there was effect modification calculating the synergy factor (SF) and relative excess risk due to interaction (RERI). RESULTS: After controlling for age, gender, education, occupation and marital status, the OR of BCG scar on the risk of leprosy was 0.10 (95% confidence interval [CI], 0.02 to 0.45), for an estimate of vaccine effectiveness of 89.5% reduced risk of leprosy (95% CI, 55.2 to 98.1). There was evidence of heterogeneity by which the effectiveness of BCG seemed stronger among younger persons (Breslow-Day and Z-test of the SF had a p<0.05), and both the RERI and SF indicated a less then multiplicative and additive interaction of BCG and younger age. CONCLUSIONS: BCG vaccination was associated with a decreased risk of leprosy in the study population, particularly in persons born after 1980.

Helicobacter pylori, Vascular Risk Factors and Cognition in U.S. Older Adults.

Previous studies suggested that Helicobacter pylori infection could be a risk factor for stroke, dementia, and Alzheimer's disease (AD). The authors examined data from participants, 60 years old and older in the Third National Health and Nutrition Examination Survey (NHANES-III) to assess the relation between Helicobacter pylori infection and results of the Mini-Mental State Examination (n = 1860) using logistic regression analysis controlling for age, gender, race/ethnicity, education, poverty and history of medically diagnosed diabetes. Moreover, we examined performance on the digit-symbol substitution test (DSST) of 1031 participants in the 1999-2000 NHANES according to their H. pylori infection status controlling for potential confounders using multiple linear regression analyses. In 1988-1991, older adults infected with CagA strains of H. pylori had a 50% borderline statistically significant increased level of cognitive impairment, as measured by low Mini-Mental State Examination (MMSE) scores (age-education adjusted prevalence ratio: 1.5; 95% confidence interval: 1.0, 2.0). In 1999-2000, older US adults infected with H. pylori scored 2.6 fewer points in the DSST than those uninfected (mean adjusted difference: -2.6; 95% confidence interval -5.1, -0.1). The authors concluded that H. pylori infection might be a risk factor for cognitive decline in the elderly. They also found that low cobalamin and elevated homocysteine were associated with cognitive impairment.

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.

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.

Underreporting of Fatal Congenital Zika Syndrome, Mexico, 2016-2017.

To determine completeness of fatal congenital Zika syndrome reporting in Mexico, we examined data from the Mexican National Institute of Statistics and Geography. We found that an estimated 50% more infants died from microcephaly attributable to congenital Zika syndrome during 2016-2017 than were reported by the existing surveillance system.

The Use of Electronic Cigarettes in Pregnancy: A Review of the Literature.

IMPORTANCE: Electronic cigarette (e-cigarette) use in pregnancy has been steadily increasing and has been hyped as being a safe alternative to cigarette smoking during pregnancy. This review discloses what is currently known about e-cigarette use in pregnancy and the effects of its use on pregnancy outcomes. OBJECTIVE: To determine what is currently known about the prevalence of e-cigarette use in pregnancy and the effects of e-cigarette use on pregnancy and perinatal/neonatal outcomes. EVIDENCE ACQUISITION: A PubMed, CINAHL, and EMBASE search was undertaken using the search terms "pregnancy" OR "pregnancy complications" OR "pregnancy outcome" OR "newborn" OR "neonate" OR "birth" AND "electronic cigarettes" OR "e-cigarettes" OR "ecigarettes" OR "vaping" OR "vape." The search was limited to the English language and between 2007 and October 12, 2017. RESULTS: The search identified 91 articles, 40 of which are the basis for this review. The prevalence of e-cigarette use is 0.6% to 15%. The amount of nicotine consumed by e-cigarette users is comparable to that consumed by cigarette smokers. Most of the animal model studies suggest a potential danger to the developing fetus primarily because of the nicotine consumed and that consumption has multiple effects on the immune system, neural development, lung function, and cardiac function. There is a widespread flawed perception that e-cigarettes are safe to use during pregnancy. CONCLUSIONS: The marketing of e-cigarette use as a safer alternative to cigarette smoking has led to an increasing use even in pregnancy. The nicotine consumed by e-cigarettes is similar to that consumed by cigarette smoking. Animal studies confirm the dangers of nicotine to the developing fetus. More research needs to be done specifically assessing e-cigarette use, pregnancy, and pregnancy outcomes. RELEVANCE: The amount of nicotine consumed in cigarette smoking is similar to the amount of nicotine consumed with e-cigarettes. The effects of nicotine exposure during fetal development are well known and include effects on multiple organ systems.

Morbidity and mortality from farm tractor-related injuries in Arkansas.

This study applied a text string search algorithm to ascertain suspect farm tractor or agricultural machinery-related injuries in data sources available for 2000-2014 in the state of Arkansas. The occurrences of tractor or other agricultural machinery-related injuries were compared with data available from the Centers for Disease Control and Prevention's National Center for Health Statistics (NCHS) and the Bureau of Labor Statistics' Census of Fatal Occupational Injuries (CFOI). For death certificates that assigned an external cause of death, the authors first collected all those that were coded as related to agricultural machinery, based on search strings for occupation and industry and a description of how the injury occurred. They then inspected each case individually and removed those that were likely unrelated to agricultural machinery. This approach significantly increased (by 7.8 times) the number of suspect agricultural machinery-related fatalities compared to the number reported to CFOI, but there was only a 17% (not statistically significant) increase compared to NCHS. All hospital records with any discharge diagnosis coded as related to agricultural machinery were selected. Descriptive analysis of the fatalities and hospital records showed a significantly increased risk among men above retirement age, peaks during the summer, and an increased risk in the Mississippi delta region. About one-third of the agricultural machinery-related fatalities were due to overturns. The use of the algorithm can improve ascertainment of fatal agricultural machinery-related injuries in Arkansas. The death records were found to be rich in data on the circumstances of the injuries, which can be used to screen for tractor-related fatalities and, if confirmed, translated into action to improve the safety of Arkansas farmers.

Electronic Nicotine Delivery Systems and Smoking Cessation in Arkansas, 2014.

OBJECTIVES: As of October 2015, evidence needed to make a recommendation about the use of electronic nicotine delivery systems (ENDS) for smoking cessation was limited. We used the 2014 Arkansas Behavioral Risk Factor Surveillance System with additional state-specific questions to determine the prevalence of ENDS use, the impact of ENDS use on smoking cessation, and beliefs about ENDS use in Arkansas. Our objectives were to determine if (1) ENDS use was associated with lower odds of quitting smoking, (2) ENDS users believed that ENDS use was not harmful to their health, and (3) ENDS users believed that switching to ENDS reduced their tobacco-related health risks. METHODS: We conducted a cross-sectional study of 4465 respondents to the Arkansas Behavioral Risk Factor Surveillance System and used weighted analyses to account for the complex survey design. We used a subset of records formed by (1) formers smokers who quitted smoking in the last 5 years and (2) current smokers to assess the odds of quitting. RESULTS: In 2014, 6.1% (95% confidence interval [CI], 5.0%-7.4%) of Arkansas adults were currently using ENDS. Of the 1083 participants who were current smokers or had quit smoking within the past 5 years, 515 (54.1%) had used ENDS. Of the 515 ENDS users, 404 (80.3%) had continued smoking. ENDS use was significantly associated with reduced odds of quitting smoking (weighted odds ratio = 0.53; 95% CI, 0.34-0.83). Although 2437 of 3808 participants (62.5%) believed that it was harmful for nonsmokers to start using ENDS and 1793 of 3658 participants (47.0%) believed that switching to ENDS did not reduce tobacco-related health risks, only 80 of 165 (41.3%) and 50 of 168 (33.9%) ENDS users shared these same respective beliefs. CONCLUSIONS: Most smokers who indicated smoking in the past 5 years and who tried ENDS did not stop smoking. ENDS use was inversely associated with smoking cessation. Tobacco cessation programs should tell cigarette smokers that ENDS use may not help them quit smoking.

Use of electronic nicotine delivery systems and recent initiation of smoking among US youth.

OBJECTIVES: We assessed whether the prevalence of recent (within a year) initiation of cigarette smoking was associated with reports of ever using electronic delivery systems (ENDS) in the National Youth Tobacco Survey (NYTS) and whether the association varied by age. METHODS: Weighted cross-sectional analysis of use of ENDS, cigarette smoking, age at interview and age at initiation of smoking collected systematically through the 2011-2013 NYTS cycles. RESULTS: In multivariate analyses those who ever used ENDS were twice as likely as nonusers of ENDS to have tried cigarette smoking in the last year (multivariate PR: 2.3; 95 % CI 1.9, 2.7). This average hid significant variations by age: a 4.1-fold increase (95 %; 2.6, 6.4) among those 11-13 years of age, compared to a smaller increase among those 16-18 years: 1.4-fold (95 % CI 1.1, 1.8). CONCLUSIONS: Use of ENDS by adolescents was associated with initiation of cigarette smoking in the last year. This association was stronger in younger adolescents.

Why U.S. epilepsy hospital stays rose in 2006.

OBJECTIVE: We observed a substantial increase in age-adjusted hospitalization rates in the United States National Hospital Discharge Survey data from 1996 to 2010. We aimed to assess reasons for this increase. METHODS: The National Hospital Discharge Survey collected data on a national sample of short-term hospital stays in nonfederal hospitals. We determined epilepsy-related discharge diagnoses by age, gender, and region using weighted analysis, and estimated age-adjusted rates and annual percent changes using regression analysis. We also looked at epilepsy as the principal discharge diagnosis in the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project. RESULTS: In the United States, on average, nearly 110,000 more admissions were reported each year with epilepsy as the principal discharge diagnosis in 2006-2010 than in 1996-2005, a 2.7-fold increase in hospitalization rates from epilepsy. During this period, there were more hospitalizations with principal discharge diagnosis of epilepsy not otherwise specified, and among older patients. The number of discharges with seizure not otherwise specified dropped dramatically after 2006, and was more evident among pediatric patients. The age-adjusted rates of hospital stays combining discharges with any mention of epilepsy (345.XX) or seizures unspecified (780.39) in seven discharge diagnoses, were similar in 1996-2005 and 2006-2010. SIGNIFICANCE: We postulate that the excess in hospitalizations with epilepsy as first discharge diagnosis in 2006-2010 in the United States was related to the changes in coding in 2006. Any use of U.S. hospital discharge data with epilepsy-related diagnosis after that date will require further validation. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Greater than 95% success with 14-day bismuth quadruple anti- Helicobacter pylori therapy: a pilot study in US Hispanics.

BACKGROUND: A combination capsule of bismuth, metronidazole, and tetracycline plus omeprazole given as 10-day therapy has an overall effectiveness of 92-93% in per-protocol analysis (Grade B) with eradication of 86-91% of metronidazole-resistant Helicobacter pylori. This study aimed to explore whether extending the duration to 14 days would improve overall effectiveness per protocol to ≥95% (Grade A) in a population in which metronidazole resistance was anticipated to exist. METHODS: A one-arm, open-label pilot study of H. pylori-infected, asymptomatic/mildly dyspeptic adults, Hispanic residents of El Paso, Texas, received a 14-day course of omeprazole, plus the combination capsule. We cultured and Gram-stained specimens obtained using a minimally invasive orogastric brush. Helicobacter pylori status was determined by (13)C-urea breath test at 4 or more weeks post-therapy. RESULTS: Forty-seven subjects (7 men and 40 women, average age 42 years) were entered. The per-protocol effectiveness was 97.1% (33/34) (95% mid-P CI: 86.3, 99.9); 100% of metronidazole-resistant strains were eradicated. Side effects were mild and self-limited but contributed to nonadherence. Therapy taken for <10 days was more likely to result in eradication failure (p < .001). Office-based orogastric brushing was well tolerated; positive cultures were obtained in 95%. Gram staining showed H. pylori-like forms in all specimens. CONCLUSIONS: This pilot study supports the concept that 14-day OBMT therapy is likely to be more efficacious for H. pylori eradication (Grade A, PP basis) than a 10-day course where metronidazole resistance is suspected. If confirmed, 14 days should be recommended in populations where metronidazole resistance is common.

Yard flooding by irrigation canals increased the risk of West Nile disease in El Paso, Texas.

PURPOSE: To investigate the effects of use of water from irrigation canals to flood residential yards on the risk of West Nile disease in El Paso, Texas. METHODS: West Nile disease confirmed cases in 2009 through 2010 were compared with a random sample of 50 residents of the county according to access to and use of water from irrigation canals by subjects or their neighbors, as well as geo-referenced closest distance between their home address and the nearest irrigation canal. A windshield survey of 600 m around the study subjects' home address recorded the presence of irrigation canals. The distance from the residence of 182 confirmed cases of West Nile disease reported in 2003 through 2010 to canals was compared with that of the centroids of 182 blocks selected at random. RESULTS: Cases were more likely than controls to report their neighbors flooded their yards with water from canals. Irrigation canals were more often observed in neighborhoods of cases than of controls. Using the set of addresses of 182 confirmed cases and 182 hypothetical controls the authors found a significant, inverse relation with risk of West Nile disease. CONCLUSIONS: Flooding of yards with water from canals increased the risk of West Nile disease.

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.