Reductions in plasma and urine mercury concentrations following N,N'bis-(2-mercaptoethyl) isophthalamide (NBMI) therapy: a post hoc analysis of data from a randomized human clinical trial.

Environmental mercury exposure possesses a significant risk to many human populations. At present there are no effective treatments for acute mercury toxicity. A new compound, N,N'bis-(2-mercaptoethyl) isophthalamide (NBMI), a lipophilic chelating agent was created to tightly/irreversibly bind mercury. A post hoc dose-dependent analysis of NBMI therapy was undertaken on data from a randomized controlled NBMI human treatment trial on 36 Ecuadorian gold miners with elevated urinary mercury concentrations. Study subjects were randomly assigned to receive 100 milligram (mg) NBMI/day, 300 mg NBMI/day, or placebo for 14 days. For each study subject daily mg NBMI dose/Kilogram (Kg) bodyweight were determined and plasma and urine mercury concentrations (micrograms (µg)/Liter (L)) on study day 1 (pre-NBMI treatment), 15 (after 14 days of NBMI treatment) and 45 (30 days after NBMI treatment) were correlated with NBMI dosing using the linear regression statistic in SAS. Regression revealed significant inverse correlations between increasing per mg NBMI/Kg bodyweight/day and reduced concentrations of urinary and plasma mercury on study day 15 (reduced by in urine = 18-20 µg/L and plasma = 2 µg/L) and study day 30 (reduced by in urine = 15-20 µg/L and plasma = 4 µg/L) and significant correlations between reductions in mercury concentrations in urine and plasma. Significant 30% reductions in urinary mercury concentrations per mg NBMI/Kg bodyweight/day administered for 14 days were observed. This study supports the dose-dependent ability of NBMI therapy to significantly reduce mercury concentrations, particularly in the urine, in an acutely mercury exposed human population. NBMI therapy should be evaluated in other mercury exposed populations.

Childhood MMR vaccination and the incidence rate of measles infection: a ten year longitudinal cohort study of American children born in the 1990s.

BACKGROUND: Measles (rubeola) is a highly contagious disease with significant morbidity/mortality. Measles-Mumps-Rubella (MMR) is a live-attenuated vaccine used in the United States (US) since the early 1970s to prevent measles infection. This retrospective longitudinal cohort study examined childhood MMR vaccination effectiveness (VE) on preventing diagnosed measles cases. METHODS: The Independent Healthcare Research Database (IHRD) is composed of non-identifiable linked eligibility and claim healthcare records prospectively generated from the Florida Medicaid system. The SAS system was utilized to examine a cohort of 101,736 persons eligible for Florida Medicaid from 1990 to 2009 and continuously eligible with ≥10 outpatient office visits during the 120-month period following birth. There were 32,870 persons (224,492 person-years) in the cohort receiving a single dose of childhood MMR vaccine (vaccinated) and 43,538 persons (434,637 person-years) in an unvaccinated cohort (no exposures to measles-containing vaccine). The frequency of diagnosed measles (ICD-9 code: 055xxx) was examined. Cox proportional hazards models evaluated MMR vaccination and diagnosed measles over time. RESULTS: MMR vaccinated cohort members were at significantly reduced risk of measles in the unadjusted (VE = 83.6, 95% CI = 67.2-91.8%) and adjusted (VE = 80.7, 95% CI = 61.5-83.9%) models as compared to the unvaccinated cohort. VE = 80% among younger MMR recipients (12-15 months), whereas VE = 90% among older MMR recipients (16-20 months) as compared to the unvaccinated cohort. CONCLUSION: Routine childhood MMR vaccination significantly reduced the incidence rate of childhood measles infections, and the VE was greater in the older recipients (16-20 months) than in the younger recipients (12-15 months).

A cross-sectional study of the relationship between blood lead levels and reported attention deficit disorder: an assessment of the economic impact on the United States.

Attention deficit disorder (ADD) is characterized by a pattern of inattention and/or impulsivity that is inconsistent with developmental level and interferes with normal functioning in at least two settings. A recent meta-analysis suggested a significant relationship between lead (Pb) exposure and attention deficit symptoms. This study evaluated the potential relationship between increasing blood Pb levels and the risk of a reported ADD diagnosis. This cross-sectional study examined a sample of 2109 persons (32,762,158 weighted-persons) between 10 and 19 years-old from the 2003-2004 National Health and Nutritional Examination Survey (NHANES). This study analyzed demographic, socioeconomic, health related-questions, and laboratory tests using survey logistic and frequency modeling in SAS. On a microgram (µg)/deciliter (dL) basis, a significant dose-response relationship between increasing blood Pb levels and the risk of a reported ADD outcome was confirmed (odds ratio (OR) = 1.237, p = 0.0227). The relationship between increasing blood Pb levels and the risk of a reported ADD remained consistent when examining covariates such as gender, race, and socioeconomic status (OR = 1.292, p = 0.0301). Control outcomes selected on an a priori basis to not be biologically plausibly linked to blood Pb levels showed no relationship with increasing blood Pb levels. This NHANES analysis revealed an estimated 380,000 persons born in the United States (US) from 1984 to 1993 were reported to have an ADD outcome as a consequence of elevated blood Pb levels and the excess lifetime costs of these persons would be about US $100 billion. Every effort should be made to eliminate childhood Pb exposure.

Mercury-associated diagnoses among children diagnosed with pervasive development disorders.

Nelson and Bauman (Pediatrics 111:674-679, 2003) previously hypothesized that pervasive developmental disorder (PDD) was not associated with mercury (Hg) exposure because the medical conditions associated with Hg exposure were not associated with PDD. A hypothesis-testing longitudinal case-control study evaluated the frequency of medically diagnosed conditions previously associated with Hg poisoning, including: epilepsy, dysarthria, failure to thrive, cerebral palsy, or contact dermatitis and other eczema among children preceding their eventual PDD diagnosis (cases) compared to controls. A retrospective examination of medical records within the Vaccine Safety Datalink (VSD) was undertaken. Cases diagnosed with PDD (n = 534) were born from 1991 to 2000 and continuously enrolled until their PDD diagnosis. Controls (n = 26,367) were born from 1991 to 1993 and continuously enrolled from birth for 7.22 years. Within the first 5 years of life, cases compared to controls were significantly (p < 0.0001) more likely to be assigned a diagnosis of contact dermatitis and other eczema (odds ratio (OR) = 2.033), dysarthria (OR = 23.992), epilepsy (OR = 5.351), failure to thrive (OR = 25.3), and cerebral palsy (OR = 4.464). Similar results were observed when the data were separated by gender. Overall, the results of the present study and recently published studies provide direct evidence supporting a link in twelve of twelve categories (100%) of Hg poisoning associated symptoms as defined by Nelson and Bauman (Pediatrics 111:674-679, 2003) and symptoms observed in those with a PDD diagnosis. The results of this study support the biological plausibility of Hg poisoning to induce PDD diagnoses and rejection of the Nelson and Bauman (Pediatrics 111:674-679, 2003) hypothesis because those with a PDD diagnosis have an increased frequency of conditions previously associated with Hg poisoning.

Thimerosal exposure and disturbance of emotions specific to childhood and adolescence: A case-control study in the Vaccine Safety Datalink (VSD) database.

BACKGROUND: This study evaluated Thimerosal-containing childhood vaccines and the risk of a diagnosis called disturbance of emotions specific to childhood and adolescence (ED). Thimerosal is an organic-mercury (Hg)-containing compound used in some vaccines. METHODS: A hypothesis-testing prospective, longitudinal case-control study evaluated Hg exposure from Thimerosal in hepatitis B vaccines administered at specific times within the first 6 months of life and its association with medically diagnosed ED (313.xx) (n = 517) in children born between 1991-2000 in comparison to controls (n = 27 491) in the Vaccine Safety Datalink (VSD) database. RESULTS: Cases diagnosed with ED were significantly more likely than controls to have received increased Hg exposure within the first month of life (odds ratio (OR) = 1.3384), the first 2 months of life (OR = 1.3367) and the first 6 months of life (OR = 2.37). When the data were separated by gender, similar significant adverse effects were observed for males, but not females. On a per microgram Hg basis, cases diagnosed with ED were significantly more likely than controls to have received increased exposure within the first 6 months of life (OR = 1.025 per microgram Hg). CONCLUSIONS: The results show a significant relationship between Hg exposure from Thimerosal-containing childhood vaccines and the subsequent risk of an ED diagnosis.

Systematic Assessment of Research on Autism Spectrum Disorder (ASD) and Mercury Reveals Conflicts of Interest and the Need for Transparency in Autism Research.

Historically, entities with a vested interest in a product that critics have suggested is harmful have consistently used research to back their claims that the product is safe. Prominent examples are: tobacco, lead, bisphenol A, and atrazine. Research literature indicates that about 80-90% of studies with industry affiliation found no harm from the product, while only about 10-20% of studies without industry affiliation found no harm. In parallel to other historical debates, recent studies examining a possible relationship between mercury (Hg) exposure and autism spectrum disorder (ASD) show a similar dichotomy. Studies sponsored and supported by industry or entities with an apparent conflict of interest have most often shown no evidence of harm or no "consistent" evidence of harm, while studies without such affiliations report positive evidence of a Hg/autism association. The potentially causal relationship between Hg exposure and ASD differs from other toxic products since there is a broad coalition of entities for whom a conflict of interest arises. These include influential governmental public health entities, the pharmaceutical industry, and even the coal burning industry. This review includes a systematic literature search of original studies on the potential relationship between Hg and ASD from 1999 to August 2015, finding that of the studies with public health and/or industry affiliation, 86% reported no relationship between Hg and ASD. However, among studies without public health and/or industry affiliation, only 21% find no relationship between Hg and ASD. The discrepancy in these results suggests a bias indicative of a conflict of interest.

A Two-Phase Case-Control Study of Autism Risk Among Children Born From the Late 1990s Through the Early 2000s in the United States.

BACKGROUND This study evaluated the hypothesis that the 1999 recommendation by the American Academy of Pediatrics (AAP) and US Public Health Service (PHS) to reduce exposure to mercury (Hg) from Thimerosal in US vaccines would be associated with a reduction in the long-term risk of being diagnosed with autism. MATERIAL AND METHODS A two-phase assessment utilizing a case (n=73) -control (n=11,783) study in the Vaccine Adverse Event Reporting System (VAERS) database (for hypothesis generating) and a more rigorous, independent matched case (n=40) -control (n=40) study (hypothesis testing) was undertaken. RESULTS Analysis of the VAERS database using logistic regression revealed that the odds ratio (OR) for being an autism case in the VAERS database significantly decreased with a more recent year of vaccination in comparison to controls (OR=0.65) from 1998 to 2003. Sex-separated analyses revealed similar significant effects for males (OR=0.62) and females (OR=0.71). Analyses of the matched case-control data revealed, using the t-test statistic, that the mean date of birth among cases diagnosed with an autism spectrum disorder (ASD) (2000.5±1.2) was significantly more in the past than in controls (2001.1±1.3). Logistic regression also revealed that the OR for being diagnosed with ASD significantly decreased with a more recent date of birth in comparison to controls (OR=0.67) from 1998-2003. CONCLUSIONS This study reveals that the risk of autism during from the late1990s to early 2000s in the US significantly decreased with reductions in Hg exposure from Thimerosal-containing childhood vaccines, but future studies should examine this phenomenon in other US populations. Vaccine programs have significantly reduced the morbidity and mortality associated with infectious disease, but Thimerosal should be removed from all vaccines.

New science challenges old notion that mercury dental amalgam is safe.

Mercury dental amalgam has a long history of ostensibly safe use despite its continuous release of mercury vapor. Two key studies known as the Children's Amalgam Trials are widely cited as evidence of safety. However, four recent reanalyses of one of these trials now suggest harm, particularly to boys with common genetic variants. These and other studies suggest that susceptibility to mercury toxicity differs among individuals based on multiple genes, not all of which have been identified. These studies further suggest that the levels of exposure to mercury vapor from dental amalgams may be unsafe for certain subpopulations. Moreover, a simple comparison of typical exposures versus regulatory safety standards suggests that many people receive unsafe exposures. Chronic mercury toxicity is especially insidious because symptoms are variable and nonspecific, diagnostic tests are often misunderstood, and treatments are speculative at best. Throughout the world, efforts are underway to phase down or eliminate the use of mercury dental amalgam.

Evidence supporting a link between dental amalgams and chronic illness, fatigue, depression, anxiety, and suicide.

The purpose of this review is to examine the evidence for a relationship between mercury (Hg) exposure from dental amalgams and certain idiopathic chronic illnesses--chronic fatigue syndrome (CFS), fibromyalgia (FM), depression, anxiety, and suicide. Dental amalgam is a commonly used dental restorative material that contains approximately 50% elemental mercury (Hg0) by weight and releases Hg0 vapor. Studies have shown that chronic Hg exposure from various sources including dental amalgams is associated with numerous health complaints, including fatigue, anxiety, and depression--and these are among the main symptoms that are associated with CFS and FM. In addition, several studies have shown that the removal of amalgams is associated with improvement in these symptoms. Although the issue of amalgam safety is still under debate, the preponderance of evidence suggests that Hg exposure from dental amalgams may cause or contribute to many chronic conditions. Thus, consideration of Hg toxicity may be central to the effective clinical investigation of many chronic illnesses, particularly those involving fatigue and depression.

Constitutional chromosomal anomalies in children, fetal alcohol syndrome, and maternal toxicant exposures: A longitudinal cohort study.

DNA alterations in gametes, which may occur either spontaneously or as a result of exposure to genotoxicants, can lead to constitutional chromosomal anomalies in the offspring. Alcohol is an established genotoxicant. The goal of this hypothesis-testing longitudinal cohort study was to evaluate the effect of significant/sustained maternal alcohol exposure on clinically diagnosed constitutional chromosomal anomalies among children diagnosed with fetal alcohol syndrome (FAS). De-identified eligibility and claim healthcare records, prospectively generated from the 1990-2012 Florida Medicaid system within the Independent Healthcare Research Database (IHRD), were analyzed. Children examined were continuously eligible with ≥ 8 outpatient office visits during the 96-month period following birth. Among these children, 377 were diagnosed with FAS and 137,135 were not. The incidence rate of chromosomal anomalies involving segregation (trisomy 13, 18, or 21, n = 625), microdeletions (microdeletion syndromes, n = 39), and point mutations (sickle-cell anemia/cystic fibrosis, n = 2570) were examined using frequency risk ratio (RR) and logistic regression (adjusted odds ratio (aOR) for sex, race, residence, socioeconomic/environmental exposure status, and birth date) models. The incidence rates of chromosomal anomalies involving segregation (RR=5.92, aOR=5.85) and microdeletions (RR=41.6, aOR=34.1) were significantly increased in the FAS cohort as compared to the non-diagnosed cohort, but there was no difference in the incidence rate of point mutations (RR=1.14, aOR=1.29). Maternal toxicant exposure should be considered in the etiology of constitutional chromosomal anomaly in offspring.

Estimated mercury vapor exposure from amalgams among American pregnant women.

This study examined the impact of mercury (Hg) vapor exposure from amalgams among all American pregnant women. Amalgam-Hg vapor exposure among 1,665,890 weighted-pregnant women (n = 37) was examined in the 2015-2020 National Health and Nutrition Examination Survey (NHANES). Correlation coefficients between amalgam surfaces and daily micrograms (µg) of urinary Hg excretion and daily µg of Hg vapor exposure from amalgams per kilogram (Kg) bodyweight were calculated. Daily Hg vapor exposure from amalgams was compared to Hg vapor safety limits. About 600,000 pregnant women (∼36%) had at least one amalgam surface. Median daily urinary Hg excretion was ∼2.5-fold higher among pregnant women with amalgams as compared to pregnant women without amalgams. A significant correlation was observed between the number of amalgam surfaces and daily urinary Hg excretion. Among pregnant women with amalgams, it was estimated that the median daily Hg vapor dose from amalgams was 7.66 µg of Hg and 0.073 µg of Hg/Kg bodyweight. Among all pregnant women, ∼28% received daily Hg vapor doses from amalgams above the least restrictive United States (US) Environmental Protection Agency (EPA) safety limit and ∼36% received above the most restrictive California (CA) EPA safety limit. Given the potential for fetal toxicological effects from prenatal Hg vapor exposure, special emphasis needs to be placed on reducing/eliminating amalgams in pregnancy/women of reproductive age and future studies should evaluate adverse pregnancy outcomes.

L-carnitine exposure and mitochondrial function in human neuronal cells.

L-Carnitine is a naturally occurring substance required in mammalian energy metabolism that functions by facilitating long-chain fatty acid entry into cellular mitochondria, thereby delivering substrate for oxidation and subsequent energy production. It has been purposed that L-carnitine may improve and preserve cognitive performance, and may lead to better cognitive aging through the life span, and several controlled human clinical trials with L-carnitine support the hypothesis that this substance has the ability to improve cognitive function. We further hypothesized that, since L-carnitine is an important co-factor of mammalian mitochondrial energy metabolism, acute administration of L-carnitine to human tissue culture cells should result in detectable increases in mitochondrial function. Cultures of SH-SY-5Y human neuroblastoma and 1321N1 human astrocytoma cells grown in 96-well cell culture plates were acutely administered L-carnitine hydrochloride, and then, mitochondrial function was assayed using the colorimetric 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt cell assay kit in a VERSAmax tunable microplate reader. Significant increases in mitochondrial function were observed when human neuroblastoma or human astrocytoma cells were exposed to 100 nM (20 µg L-carnitine hydrochloride/L) to 100 µM (20 mg L-carnitine hydrochloride/L) concentrations of L-carnitine hydrochloride in comparison to unexposed cells, whereas no significant positive effects were observed at lower or higher concentrations of L-carnitine hydrochloride. The results of the present study provide insights for how L-carnitine therapy may significantly improve human neuronal function, but we recommend that future studies further explore different derivatives of L-carnitine compounds in different in vitro cell-based systems using different markers of mitochondrial function.

Handgrip strength in autism spectrum disorder compared with controls.

The study examined handgrip strength in participants diagnosed with an autism spectrum disorder (ASD) as compared with neurotypical children. Thirty-three children, aged 2-17 years, with an ASD and 33 gender-, race-, and age-matched neurotypical controls were tested using a handgrip dynamometer. The handgrip strength in participants with an ASD was significantly (p < 0.0001) lower than the neurotypical controls. The mean handgrip strength was 39.4 ± 17.7 kPa in children with ASD and 65.1 ± 26.7 kPa in controls. The results support the hypothesis that children with an ASD have significantly poorer handgrip strength as compared with neurotypical children. Because the handheld dynamometer has been shown to be a valid tool for measuring overall muscle strength, the results suggest that children with ASD have muscle weakness. Future studies are needed to determine the extent of muscle weakness in ASD, its ramifications, and the possible benefits of muscle strengthening. The present study provides support for the use of handgrip strength as a tool for the assessment of targeted treatment in ASD.

Urine glyphosate exposure and serum sex hormone disruption within the 2013-2014 National Health and Nutrition Examination survey (NHANES).

Glyphosate-based herbicides (GBHs) are one of the most commonly used herbicides worldwide. Numerous in vitro and in vivo model system studies have demonstrated endocrine-disrupting chemical (EDC) properties associated with glyphosate/GBH exposure. The present hypothesis-testing study evaluated the potential inverse dose-dependent relationship between increasing urinary glyphosate and decreasing concentrations of blood sex hormones. Demographic and newly available lab test data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) were analyzed with survey regression modeling (adjusted for age, gender, race, and country of birth) in Statistical Analysis System (SAS) software. A total of 225, 615, 858 weighted-persons (sample n = 2130 persons) were examined for concentrations of urinary glyphosate and serum sex hormones (including: total testosterone, total estradiol, and sex hormone binding globulin (SHBG)) among males and females, 6 years-old or older. This study revealed about 82% of the population of the United States examined had detectable urinary concentrations of glyphosate. A significant inverse correlation between concentrations of glyphosate and total estradiol and a trend towards an inverse correlation between concentrations of glyphosate and total testosterone were observed. Concentrations of SHBG and glyphosate did not correlate. Ratios of total testosterone:SHBG and total estradiol:SHBG (estimating the fraction of active sex hormones in the blood) were significantly inversely correlated with urinary concentrations of glyphosate. This epidemiological study associates widespread and ongoing glyphosate/GBH exposures with human endocrine-disruptions. Future studies should examine these phenomena in other databases and other endocrine-related disorders.

Colon Cancer Risk Following Intestinal Clostridioides difficile Infection: A Longitudinal Cohort Study.

Background: The gut microbiome may play an important role in the etiology and progression of colon cancer. The present hypothesis-testing study compared the colon cancer incidence rate among adults diagnosed with intestinal Clostridioides (formerly Clostridium) difficile (Cdiff) (the Cdiff cohort) to adults not diagnosed with intestinal Cdiff infection (the non-Cdiff cohort). Methods: De-identified eligibility and claim healthcare records within the Independent Healthcare Research Database (IHRD) from a longitudinal cohort of adults (the overall cohort) enrolled in the Florida Medicaid system between 1990 through 2012 were examined. Adults with ≥ 8 outpatient office visits over 8 years of continuous eligibility were examined. There were 964 adults in the Cdiff cohort and 292,136 adults in the non-Cdiff cohort. Frequency and Cox proportional hazards models were utilized. Results: Colon cancer incidence rate in the non-Cdiff cohort remained relatively uniform over the entire study period, whereas a marked increase was observed in the Cdiff cohort within the first 4 years of a Cdiff diagnosis. Colon cancer incidence was significantly increased (about 2.7-fold) in the Cdiff cohort (3.11 per 1,000 person-years) compared to the non-Cdiff cohort (1.16 per 1,000 person-years). Adjustments for gender, age, residency, birthdate, colonoscopy screening, family history of cancer, and personal history of tobacco abuse, alcohol abuse/dependence, drug abuse/dependence, and overweight/obesity, as well as consideration of diagnostic status for ulcerative and infection colitis, immunodeficiency, and personal history of cancer did not significantly change the observed results. Conclusions: This is the first epidemiological study associating Cdiff with an increased risk for colon cancer. Future studies should further evaluate this relationship.

A quantitative evaluation of brain dysfunction and body-burden of toxic metals.

BACKGROUND: Toxic metal exposure (e.g. Hg, Pb, As) exposure is known to induce significant adverse effects on human brain function. The aim this study was to assess toxic metal body-burden in relation to potential brain dysfunction in patients diagnosed with neurological disorders (NDs). MATERIAL/METHODS: The Liberty Institutional Review Board (Deland, FL) approved the present study. Quantitative, fractionated, random urinary porphyrin testing (µg/L) from the Clinical Laboratory Improvement Act/Amendment (CLIA)-approved Laboratory Corporation of America (LabCorp) and cortical perfusion index (CPi) values from single-photon-emission-computed-tomography (SPECT) brain scans were employed to evaluate a prospective cohort of qualifying patients with diagnosed NDs (n=52) presenting for medical care at an endocrinology practice in the Cincinnati, OH area. RESULTS: Patients with more severe in comparison to mild brain dysfunction had significant increases in the mean urinary concentration of uroporphyrins (uP), coproporphyrins I (cP I), and total cP (cP I + III), as well as a trend towards significantly increased mean urinary concentration of pentacarboxyporphyins (5cxP) and cP III. A significant positive correlation between Hg body-burden associated porphyrins (5cxP + cP I + cP III) and increased brain dysfunction was observed. CONCLUSIONS: The present study associated brain dysfunction with Hg body-burden in a cohort of patients diagnosed with NDs, but the contributions of other heavy metals or genetic factors cannot be ruled-out. Additional studies should be conducted to evaluate the consistency of the present findings with examinations of other populations.

The temporal relationship between RotaTeq immunization and intussusception adverse events in the Vaccine Adverse Event Reporting System (VAERS).

BACKGROUND: In August of 2006, the Advisory Committee on Immunization Practices (ACIP) recommended RotaTeq for routine vaccination of US infants. The hypothesis tested in the present study is that rotavirus vaccines are associated with an increased risk of intussusception adverse events (AEs) characterized by an onset in a biologically plausible a priori identified temporal period post-vaccination (days 3 to 7). MATERIAL/METHODS: The Vaccine Adverse Event Reporting System (VAERS) updated as of December 28, 2010 was analyzed. RESULTS: Following RotaTeq vaccination, a significantly (p<0.001) higher percentage of AEs were classified as serious, permanently disabling, resulted in hospitalizations, or were life-threatening among intussusception AEs in comparison to the total AE reports (removing intussusception AE reports) submitted to VAERS. A significantly greater portion of intussusception AEs in comparison to the portion of total AE reports (removing intussusception AE reports) were reported to VAERS in the onset interval from 3 to 7 days post-RotaTeq vaccination than within the onset interval from 1 to 2 days post-RotaTeq vaccination (78.7% vs. 29.1%, risk ratio=2.7, 95% CI=2.4-3.0, p<0.0001). It was assumed in our onset time-trend analyses of the distribution of AEs following Rota-Teq vaccination that the AE's should be equally likely to be reported with an onset time for each day, from 1 to 9 days post-vaccination or, alternatively, should follow similar daily proportions as observed for total AEs reports (removing intussusception AE reports). Results of this onset time-trend analyses of the distribution of intussusception AEs reported to VAERS following Rota-Teq vaccination revealed significant differences (p<0.001) from our expectations. Consistent and similarly remarkable trends were observed for intussusception AE reports associated with RotaShield vaccine. CONCLUSIONS: The present study significantly associates RotaTeq vaccination with intussusception AEs.

Childhood MMR Vaccination Effectiveness Against Rubella: A Longitudinal Cohort Study.

The vaccine effectiveness (VE) of childhood measles-mumps-rubella (MMR) vaccine to reduce childhood rubella infections in the US during the 1990s/2000s was undertaken in a retrospective longitudinal cohort study. SAS and StatsDirect software were utilized to examine non-identifiable linked eligibility and claim healthcare records prospectively generated from the Florida Medicaid system in the Independent Healthcare Research Database (IHRD). A total of 33 839 children received a single MMR vaccination (vaccinated) and 44 154 children never received a rubella-containing vaccine (unvaccinated) were continuously eligible from 1990 to 2009 for Florida Medicaid within the first 10 years following birth. Cox proportional hazards models determined VE against diagnosed rubella (ICD-9 code: 056.xx). Children receiving MMR were at significantly reduced risk of rubella in unadjusted (VE = 80.7%, 95% confidence interval = 73.7%-85.8%) and adjusted (VE = 78.6%, 95% confidence interval = 70.8%-84.3%) models as compared to unvaccinated children. Between 1991 and 2009, in the combined vaccinated-unvaccinated cohort examined on a yearly basis, a significant inverse correlation between increasing MMR vaccine population coverage and a decreasing incidence rate of diagnosed rubella was observed. This first large-scale population epidemiological study supports the routine use childhood MMR vaccination to significantly reduce childhood rubella infections and also supports its ability to induce "herd immunity." This study, coupled with a recently published epidemiological study showing childhood MMR vaccination significantly reduced measles infections, provide powerful epidemiological evidence strongly supporting MMR vaccination as an effective tool to improve public health.