Microbiological Investigations of ReNu Plastic Bottles and the 2004 to 2006 ReNu With MoistureLoc-Related Worldwide Fusarium Keratitis Event.

PURPOSES: The purposes of this study were to determine whether the contact lens solution RevitaLens Ocutec (containing the antimicrobial agents alexidine and polyquaternium-1) would inhibit Fusarium organisms when heated in ReNu plastic bottles; whether alexidine would inhibit Fusarium organisms when heated in non-ReNu plastic bottles; and whether an alexidine-neutralizing compound leaches from heated ReNu bottles. METHODS: RevitaLens and an alexidine solution (0.00045%), previously stored in ReNu bottles at room temperature (RT) and 56°C, were incubated with 7 different Fusarium organisms. The alexidine solution was similarly stored in seven non-ReNu plastic bottles and incubated with these same organisms. To determine if an alexidine-neutralizing compound might be leaching from heated ReNu bottles, phosphate-buffered saline (PBS) was incubated at RT and 56°C in ReNu bottles, combined with alexidine, and then tested for anti-Fusarium capability. RESULTS: After being heated in ReNu bottles, RevitaLens retained its anti-Fusarium capability, whereas the alexidine solution did not. The alexidine solution heated in seven non-ReNu plastic bottles retained its anti-Fusarium capability. The alexidine solution retained its anti-Fusarium capability when incubated with a PBS solution that had been heated in ReNu bottles, indicating, microbiologically, that an alexidine-neutralizing compound did not leach from the heated ReNu bottle. CONCLUSIONS: Alexidine uniquely fails to inhibit Fusarium organisms when heated in a plastic ReNu bottle, but not in seven other plastic bottles, whereas the anti-Fusarium capability of RevitaLens (containing the antimicrobial agents alexidine and polyquaternium-1) is unaffected by heating in a ReNu bottle. There does not seem to be an alexidine-neutralizing compound leaching from heated ReNu bottles. An interaction between alexidine and its heated ReNu bottle may have been a critical factor in the worldwide ReNu with MoistureLoc-related Fusarium keratitis event of 2004 to 2006.

The networks of human gut microbe-metabolite associations are different between health and irritable bowel syndrome.

The goal of this study was to determine if fecal metabolite and microbiota profiles can serve as biomarkers of human intestinal diseases, and to uncover possible gut microbe-metabolite associations. We employed proton nuclear magnetic resonance to measure fecal metabolites of healthy children and those diagnosed with diarrhea-predominant irritable bowel syndrome (IBS-D). Metabolite levels were associated with fecal microbial abundances. Using several ordination techniques, healthy and irritable bowel syndrome (IBS) samples could be distinguished based on the metabolite profiles of fecal samples, and such partitioning was congruent with the microbiota-based sample separation. Measurements of individual metabolites indicated that the intestinal environment in IBS-D was characterized by increased proteolysis, incomplete anaerobic fermentation and possible change in methane production. By correlating metabolite levels with abundances of microbial genera, a number of statistically significant metabolite-genus associations were detected in stools of healthy children. No such associations were evident for IBS children. This finding complemented the previously observed reduction in the number of microbe-microbe associations in the distal gut of the same cohort of IBS-D children.

Analysis of patterns of patient compliance after an abnormal Pap smear result: the influence of demographic characteristics on patient compliance.

OBJECTIVE: This study aimed to determine population characteristics that correlate to suboptimal follow-up after an abnormal cervical cytology result. MATERIALS AND METHODS: Nonpregnant women, ages 21 to 65 years, with newly diagnosed abnormal cervical cytology result between January 2009 and January 2012 at an urban clinic were eligible for inclusion in this retrospective chart review. Cervical cytology data and demographic characteristics such as age, ethnicity, employment, marital and smoking status, health insurance and number of pregnancies were abstracted from electronic medical record. A log-linear model was used to determine which factors influenced patient compliance. RESULTS: Of the total of 206 women, 78 (37.9%) had optimal follow-up and 128 (62.1%) had suboptimal follow-up. The 3 variables that were statistically significant in influencing patient follow-up after adjusted analyses included severity of cytology result (p = .0013), ethnicity (p = .02), and employment status (p = .0159). The risk ratio for optimal follow-up for those with severe cytology result was 1.81; for the non-whites, 1.77; and for the employed, 1.53. CONCLUSIONS: Ethnicity, severity of cervical cytology result, and employment status play an important role in patient follow-up after an abnormal cervical cytology result. Detecting trends in our patient population that influence adherence to follow-up will help health care providers formulate strategies that target this problem.

Quantitative profiling of gut microbiota of children with diarrhea-predominant irritable bowel syndrome.

OBJECTIVES: Human intestinal microbiota has a number of important roles in human health and is also implicated in several gastrointestinal disorders. The goal of this study was to determine the gut microbiota in two groups of pre- and adolescent children: healthy volunteers and children diagnosed with diarrhea predominant irritable bowel syndrome (IBS-D). METHODS: Phylogenetic Microbiota Array was used to obtain quantitative measurements of bacterial presence and abundance in subjects ' fecal samples. We utilized high-throughput DNA sequencing, quantitative PCR, and fluorescent in situ hybridization to confirm microarray findings. RESULTS: Both sample groups were dominated by the phyla Firmicutes, Bacteroidetes, and Actinobacteria, which cumulatively constituted 91 % of overall sample composition on average. A core microbiome shared among analyzed samples encompassed 55 bacterial phylotypes dominated by genus Ruminococcus ; members of genera Clostridium , Faecalibacterium, Roseburia, Streptococcus , and Bacteroides were also present. Several genera were found to be differentially abundant in the gut of healthy and IBS groups: levels of Veillonella , Prevotella , Lactobacillus , and Parasporo bacterium were increased in children diagnosed with IBS, whereas members of Bifidobacterium and Verrucomicrobium were less abundant in those individuals. By calculating a nonparametric correlation matrix among abundances of different genera in all samples, we also examined potential associations among intestinal microbes. Strong positive correlations were found between abundances of Veillonella and both Haemophilus and Streptococcus , between Anaerovorax and Verrucomicrobium , and between Tannerella and Anaerophaga . CONCLUSIONS: Although at the higher taxonomical level gut microbiota was similar between healthy and IBS-D children, specific differences in the abundances of several bacterial genera were revealed. Core microbiome in children was dominated by Clostridia. Putative relationships identified among microbial genera provide testable hypotheses of cross-species associations among members of human gut microbiota

Pan-antimicrobial failure of alexidine as a contact lens disinfectant when heated in Bausch & Lomb plastic containers: implications for the worldwide Fusarium keratitis epidemic of 2004 to 2006.

OBJECTIVE: ReNu with MoistureLoc (ReNuML), containing the antimicrobial agent alexidine 0.00045%, was associated with the Fusarium keratitis epidemic of 2004 to 2006. Although a single-point source contamination was ruled out, only Fusarium organisms were reported during the outbreak. This study investigated whether the reported loss of antimicrobial effectiveness toward Fusarium of ReNuML after exposure to heat in high-density polyethylene (HDPE) plastic containers could also be demonstrated with other common fungal and bacterial agents of keratitis. METHODS: A buffered solution of alexidine 0.00045% was incubated in glass and ReNu HDPE plastic containers at room temperature (RT) and 56°C for 4 weeks, serially diluted, and tested for its ability to inhibit the growth of 20 bacterial isolates, 12 non-Fusarium fungal isolates, and 7 Fusarium isolates originally involved in the keratitis epidemic. RESULTS: A statistically significant loss of antimicrobial capability was seen with all fungi, all gram-positive bacteria, and all isolates of Klebsiella when alexidine 0.00045% was incubated at 56°C in ReNu HDPE containers compared with RT or glass incubation (P≤0.0001). CONCLUSIONS: Heating of an alexidine solution in ReNu HDPE plastic (but not glass) containers results in the same loss of anti-Fusarium activity as reported when testing the original ReNuML solution. This loss of inhibitory activity is not specific to Fusarium and occurs with other fungi and bacteria that cause keratitis. The reasons for the lack of reports of bacterial and/or non-Fusarium fungal keratitis during the original Fusarium keratitis epidemic remain unclear at this time.

Distal gut microbiota of adolescent children is different from that of adults.

Human intestinal microbiota plays a number of important roles in human health and is also implicated in several gastrointestinal disorders. Although the diversity of human gut microbiota in adults and in young children has been examined, few reports of microbiota composition are available for adolescents. In this work, we used Microbiota Array for high-throughput analysis of distal gut microbiota in adolescent children 11-18 years of age. Samples obtained from healthy adults were used for comparison. Adolescent and adult groups could be separated in the principal components analysis space based on the relative species abundance of their distal gut microbiota. All samples were dominated by class Clostridia. A core microbiome of 46 species that were detected in all examined samples was established; members of genera Ruminococcus, Faecalibacterium, and Roseburia were well represented among core species. Comparison of intestinal microbiota composition between adolescents and adults revealed a statistically significantly higher abundance of genera Bifidobacterium and Clostridium among adolescent samples. The number of detected species was similar between sample groups, indicating that it was the relative abundances of the genera and not the presence or absence of a specific genus that differentiated adolescent and adult samples. In summary, contrary to the current belief, this study suggests that the gut microbiome of adolescent children is different from that of adults.

Effects of time, temperature, and storage container on the growth of Fusarium species: implications for the worldwide Fusarium keratitis epidemic of 2004-2006.

OBJECTIVE: To demonstrate the effects of time, temperature, and container properties on the ability of ReNu with MoistureLoc (ReNuML; contains the antimicrobial agent alexidine) to inhibit growth of Fusarium species. METHODS: ReNu with MoistureLoc was stored in its Bausch & Lomb (Rochester, New York) plastic or similarly sized glass containers for 1 and 4 weeks at room temperature, 42°C, and 56°C, and then tested for its ability to inhibit growth of 7 Fusarium isolates. RESULTS: ReNu with MoistureLoc stored in glass containers for 1 or 4 weeks at all 3 temperatures demonstrated no significant fungistatic deterioration. However, ReNuML stored at 56°C in its Bausch & Lomb plastic container demonstrated a statistically significant fungistatic deterioration compared with room temperature storage in its original plastic container or with glass container storage at any temperature. CONCLUSION: When exposed to elevated storage temperature, it appears that an interaction between ReNuML and its Bausch & Lomb plastic container adversely affects the fungistatic properties of ReNuML, which could have contributed to the Fusarium keratitis epidemic of 2004 through 2006.

A retrospective statistical analysis of the Fusarium keratitis epidemic of 2004-2006.

PURPOSE: A retrospective statistical analysis of the Fusarium keratitis epidemic of 2004-2006 was performed. METHODS: Poisson and binomial probability distributions were performed in conjunction with statistical data reported from Singapore's Fusarium keratitis outbreak in order to identify the earliest theoretical point in time that this outbreak and its cause could have been recognized. RESULTS: The outbreak in Singapore could, theoretically, have been recognized after only three months (three cases), P = 0.0067. The cause of the Singapore outbreak could, theoretically, have been determined after only four months (five cases), P = 0.0024. CONCLUSIONS: The worldwide Fusarium keratitis epidemic of 2004-2006 could, theoretically, have been recognized much earlier by the application of basic statistical methods to the outbreak in Singapore. The lessons learned from this analysis may help prevent future epidemics.

Matched samples logistic regression in case-control studies with missing values: when to break the matches.

Simulated data sets are used to evaluate conditional and unconditional maximum likelihood estimation in an individual case-control design with continuous covariates when there are different rates of excluded cases and different levels of other design parameters. The effectiveness of the estimation procedures is measured by method bias, variance of the estimators, root mean square error (RMSE) for logistic regression and the percentage of explained variation. Conditional estimation leads to higher RMSE than unconditional estimation in the presence of missing observations, especially for 1:1 matching. The RMSE is higher for the smaller stratum size, especially for the 1:1 matching. The percentage of explained variation appears to be insensitive to missing data, but is generally higher for the conditional estimation than for the unconditional estimation. It is particularly good for the 1:2 matching design. For minimizing RMSE, a high matching ratio is recommended; in this case, conditional and unconditional logistic regression models yield comparable levels of effectiveness. For maximizing the percentage of explained variation, the 1:2 matching design with the conditional logistic regression model is recommended.

Comparison of male and female breast cancer incidence trends, tumor characteristics, and survival.

PURPOSE: To compare male and female breast cancer and to determine the predictors of tumor characteristics and survival in both genders. METHODS: Male (n = 2923) and female breast cancer cases (n = 442,500) from the Surveillance, Epidemiology and End Results (SEER) registry were analyzed. Joinpoint regression was performed to detect changes in incidence trends from 1973 to 2001. Multiple logistic regression was used to regress each of four outcome variables (STAGE, LATERALITY, ESTROGEN, and PROGESTERONE RECEPTOR STATUS) on four demographic variables. Cox proportional hazards regression modeling was used to determine significant predictors of death of breast cancer after adjusting for demographic factors. RESULTS: Both men and women aged less than 50 years were at higher risk for advanced breast cancers. Males were at higher risk than females for advanced tumors among non-whites. The risk of breast cancer death among all cases was lower for each 10-year increase in age by 2%, higher for those who are unmarried than for those who are married by 12% and 13% higher for non-whites than for whites. CONCLUSIONS: Some important gender differences were detected with respect to factors associated with tumor characteristics, but gender was not a significant predictor of survival after adjusting for the other demographic variables.