The impact of monitoring techniques on progression to chronic breast cancer-related lymphedema: a meta-analysis comparing bioimpedance spectroscopy versus circumferential measurements.

BACKGROUND: Chronic breast cancer-related lymphedema (BCRL) is a potentially serious complication following treatment. Monitoring for progression to BCRL may allow for earlier detection and intervention, reducing the rate of progression to chronic BCRL. Therefore, the purpose of this meta-analysis is to evaluate the impact of monitoring techniques on the incidence of chronic BCRL among patients monitored by bioimpedance spectroscopy (BIS) and circumference as compared to background rates. METHODS: Eligible peer-reviewed studies from PubMed, CINHAL, or Google Scholar that were published in English from 2013 onward and conducted in North America, Europe, or Oceania. Incidence rates abstracted from studies were classified by BCRL monitoring method: background (no standardized BIS or circumference assessments), BIS or circumference. A random-effects model was used to calculate a pooled annualized estimate of BCRL incidence while accounting for clinical and methodological heterogeneity. Subgroup analyses examined differences in duration of follow-up as well as breast and axillary surgery. RESULTS: 50 studies were included, representing over 67,000 women. The annualized incidence of BCRL was 4.9% (95% CI: 4.3-5.5) for background studies (n = 35), 1.5% (95% CI: 0.6-2.4) for BIS-monitored studies (n = 7), and 7.7% (95% CI: 5.6-9.8) for circumference-monitored studies (n = 11). The cumulative BCRL incidence rate in BIS-monitored patients was 3.1% as compared to 12.9% with background monitoring (69% reduction) and 17.0% with circumference-monitored patients (81% reduction). CONCLUSIONS: Evidence suggests that monitoring with BIS allowing for early intervention significantly reduces the relative risk of chronic BCRL with a 69% and 81% reduction compared to background and circumference, respectively. Circumference monitoring did not appear to provide a benefit with respect to chronic BCRL incidence. Based on these results, BIS should be considered for BCRL screening in order to detect subclinical BCRL and reduce rates of chronic BCRL, particularly in high-risk patients.

The CHOICES Study: Facility Level Comparative Cost, Resource Utilization, and Outcomes Analysis of Myomectomy Compared to Transcervical Fibroid Ablation.

PURPOSE: The CHOICES study compared short-term resource utilization, facility costs, and perioperative patient outcomes between transcervical fibroid ablation (TFA) with the Sonata® system and myomectomy through a case-matched comparative trial design. This is the first facility-level comparative study conducted for TFA. PATIENTS AND METHODS: The study enrolled 88 patients from 4 centers equally divided among the two cohorts. The TFA arm consisted of 44 women who had enrolled in the SONATA Pivotal IDE trial, whereas the myomectomy arm included 44 patients who were identified through retrospective case-matching to the enrolled SONATA patients at the same 4 centers. RESULTS: TFA had a significantly lower mean operating room duration (90 minutes) and length of stay (5.2 hours) than myomectomy (143 minutes and 45.8 hours, respectively). The average total mean facility costs for TFA procedure ($7,563) were significantly lower than those associated with myomectomy ($11,425; p=0.002). TFA mean facility costs were also compared with other stratifications of myomectomy (inpatient or outpatient and surgical route). TFA facility costs were significantly lower than that associated with inpatient, abdominal, or laparoscopic myomectomy (all p<0.001). CONCLUSION: TFA using the Sonata system has a significantly shorter operating room time and length of stay than myomectomy for the treatment of symptomatic uterine fibroids. All procedure, anesthesia, laboratory, pathology, and pharmacy costs were significantly higher for myomectomy as compared to TFA. TFA was also associated with significantly lower facility procedure-related costs compared to myomectomy, including inpatient, abdominal, or laparoscopic myomectomy.

The INSPIRE Comparative Cost Study: 12-Month Health Economic and Clinical Outcomes Associated with Hysterectomy, Myomectomy, and Treatment with the Sonata System.

PURPOSE: The INSPIRE study compared perioperative and 12-month health economic and clinical outcomes associated with hysterectomy, myomectomy, and sonography-guided transcervical fibroid ablation (TFA) using the Sonata® system. PATIENTS AND METHODS: Cost and health care resource utilization (HCRU) data for TFA were obtained from a prospective, multicenter, single-arm clinical trial. Data for hysterectomy and myomectomy arms were derived from the Truven Health MarketScan commercial payer claims database. The Truven data was used to determine health economic outcomes and costs for the hysterectomy and myomectomy arms. For each arm, payer perspective costs were estimated from the available charge and HCRU data. RESULTS: TFA with Sonata had significantly lower mean length of stay (LOS) of 5 hrs versus hysterectomy (73 hrs) or myomectomy (79 hrs; all p< 0.001). The average payer cost for TFA treatment, including the associated postoperative HCRU was $8,941. This was significantly lower compared to hysterectomy ($24,156) and myomectomy ($22,784; all p< 0.001). In the TFA arm, there were no device- or procedure-related costs associated with complications during the peri- or postoperative time frame. TFA subjects had significantly lower costs associated with complications, prescription medications, and radiology. CONCLUSION: Compared to hysterectomy and myomectomy, TFA treatment with the Sonata system was associated with significantly lower index procedure cost, complication cost, and LOS, contributing to a lower total payer cost through 12 months.

First trimester ondansetron exposure and risk of structural birth defects.

This study investigates risk of specific structural birth defects associated with ondansetron exposure during the first trimester in a large US commercially-insured population. Medical claims data were obtained from Truven Health Analytics for 864,083 mother-infant pairs from 2000 to 2014. Logistic regression was used to measure the association between first trimester exposure to ondansetron and risk of cardiac defects, orofacial clefts and other specific structural defects in offspring. First trimester exposure to ondansetron was associated with increased risk of cardiac (OR: 1.52 95% CI: 1.35-1.70) and orofacial cleft defects (OR: 1.32 95% CI: 0.76-2.28) in offspring compared to women with no antiemetic exposure during pregnancy. This analysis addresses limitations of prior studies including limited power, exposure misclassification, and generalizability to the US population. In a large, US population we found a statistically significant association between early pregnancy ondansetron exposure and specific structural birth defects in offspring.

Meta-Analysis of Local Invasive Breast Cancer Recurrence After Electron Intraoperative Radiotherapy.

BACKGROUND: Electron intraoperative radiotherapy (IORT) can be used during breast conserving surgery to treat early-stage invasive breast cancer. Using data from current clinical and observational studies, this study aimed to assess the impact of single-fraction electron IORT on local recurrence rates. METHODS: Studies on single-fraction electron IORT during breast conserving surgery were identified through a search of PubMed and Google Scholar, as well as through secondary referencing. Local recurrence rate was the main outcome of interest. A meta-analysis of proportions using a binomial distribution to model the within-study variability and a random effects model was conducted to estimate a pooled local recurrence rate. To estimate a 5-year recurrence rate, a single-sample Poisson-normal model was applied to model the probability of events occurring during a fixed period (60 months). RESULTS: The study identified 13 publications. The analysis demonstrated a pooled monthly local recurrence rate of 0.02% per person-month (95% confidence interval CI 0.00-0.06%) for the studies with a follow-up period shorter than 5 years, 0.03% per person-month (95% CI 0.02-0.06%) for studies with a follow-up period of 5 years or longer, and 0.02% per person-month (95% CI 0.01-0.04%) overall. Based on this model, the predicted 5-year local recurrence rate was 2.7% (range 1.9-3.7%). CONCLUSIONS: According to the published literature, the rate of breast cancer local recurrence after electron IORT was 0.02% per person-month, with an adjusted 5-year recurrence rate of 2.7%. These findings support the recent guidelines from the American Society for Radiation Oncology (ASTRO) supporting the use of electron IORT for low-risk patients.

Building a basis for action: enhancing public health surveillance of vision impairment and eye health in the United States.

PURPOSE: To examine the ability of current surveillance systems to assess and monitor disparities in: (1) vision impairment, (2) eye disease, (3) vision-related functioning, (4) access to vision and eye care, and (5) access to supports and services for those needing vision rehabilitation. DESIGN: Review of surveillance systems and instruments. METHODS: We defined surveys and surveillance systems as data collection systems that used an active survey or data abstraction instrument, regardless of the sampling unit, and excluded strictly administrative data sources. We assessed 8 surveys against key surveillance attributes of representativeness, flexibility, and timeliness, as well as their contribution to establishing a national vision surveillance system. RESULTS: The key challenges facing a national vision surveillance system are: (1) the lack of consistent outcome data with adequate sample size and coverage to enable identification and tracking of vision health disparities, (2) lack of standardized data elements, and (3) a paucity of data that influence disability such as behavioral and environmental data. CONCLUSIONS: Current systems for assessing and monitoring vision health in the United States are limited and do not provide adequate information to guide interventions and policy decisions. Vision surveillance can help to document the burden of the condition, to identify high-risk populations, to develop strategies to reduce the individual and societal burden, and to guide public health programs and policies. Existing surveillance systems could be enhanced by integrating data and by periodically including patient-reported outcomes measurements including, but not limited to, specific barriers for people with vision impairment and related disabilities.

Disparities in adult vision health in the United States.

PURPOSE: To review the existing knowledge on vision health disparities in major adult vision health outcomes (age-related macular degeneration, diabetic retinopathy, glaucoma, cataract, refractive errors) and visual impairment and to identify knowledge gaps as related to the development of enhanced vision health surveillance in the United States. DESIGN: Literature review. METHODS: Analysis of relevant publications in the peer-reviewed literature. RESULTS: Prevalence data on vision health outcomes is limited to findings from a few key population-based studies. Study populations are not representative of all persons living in the United States. Vision loss and visual impairment are more common with age, and there is racial variation in the specific causes of vision loss (underlying health conditions). Women are at greater risk of vision loss than men (even after adjusting for age). Vision-related disability and disparities in visual outcomes are monitored poorly at present. CONCLUSIONS: Data to assess and monitor trends in vision health disparities in the United States are not collected presently in a systematic fashion. This lack of data limits public health efforts to overcome barriers to eye care use and to improve vision outcomes.

Polymorphisms in the novel gene acyloxyacyl hydroxylase (AOAH) are associated with asthma and associated phenotypes.

BACKGROUND: The gene encoding acyloxyacyl hydroxylase (AOAH), an enzyme that hydrolyzes secondary fatty acyl chains of LPS, is localized on chromosome 7p14-p12, where evidence for linkage to total IgE (tIgE) concentrations and asthma has been previously reported. OBJECTIVE: We hypothesized that variants in AOAH are associated with asthma and related phenotypes. Because both AOAH and soluble CD14 respond to LPS, we tested for gene-gene interaction. METHODS: We investigated the association between 28 single nucleotide polymorphisms throughout the AOAH gene and asthma, concentrations of tIgE, the ratio of IL-13/IFN-gamma, and soluble CD14 levels among 125 African Caribbean, multiplex asthmatic pedigrees (n = 834). Real-time PCR was used to assess whether AOAH cDNA expression differed with AOAH genotype. RESULTS: Significant effects were observed for all 4 phenotypes and AOAH markers in 3 distinct regions (promoter, introns 1-6, and the intron 12/exon 13 boundary/intron 13 region) by means of single-marker and haplotype analyses, with the strongest evidence for a 2-single-nucleotide-polymorphism haplotype and log[tIgE] (P = .006). There was no difference in AOAH expression levels by AOAH genotype for any of the markers. Comparing genotypic distributions at both the AOAH marker rs2727831 and CD14(-260)C >T raises the possibility of gene-gene interaction (P = .006-.036). CONCLUSION: Our results indicate that polymorphisms in markers within the AOAH gene are associated with risk of asthma and associated quantitative traits (IgE and cytokine levels) among asthmatic subjects and their families in Barbados, and there is an interactive effect on tIgE and asthma concentrations between an AOAH marker and the functional CD14(-260)C >T polymorphism. CLINICAL IMPLICATIONS: AOAH is a novel innate immunity candidate gene associated with asthma and related phenotypes in an African ancestry population.

Polymorphisms in the novel gene acyloxyacyl hydoxylase (AOAH) are associated with asthma and associated phenotypes

BACKGROUND: The gene encoding acyloxyacyl hydrolase (AOAH), an enzyme that hydrolyzes secondary fatty acyl chains of LPS, is localised on chromosome 7p14-p12, where evidence for linkage to total IgE (tIgE) concentrations and asthma has been previously reported. OBJECTIVE: We hypothesized that variants in AOAH are associated with asthma and related phenotypes. Because both AOAH and soluble CD14 respond to LPS, we tested for gene-gene interaction. METHODS: We investigated the association between 28 single nucleotide polymorphisms throughout the AOAH gene and asthma, concentrations of tIgE, the ratio of IL-13/IFN-y, and soluble CD14 levels among 125 African Caribbean, multiplex asthmatic pedigrees (n=834). Real-time PCR was used to assess whether AOAH cDNA expression differed with AOAH genotype. RESULTS: Significant effects were observed for all 4 phenotypes and AOAH markers in 3 distinct regions (promoter, introns 1-6, and the intron 12/exon 13 boundary/intron 13 region) by means of single-marker and haplotype analyses, with the strongest evidence for a 2-single-nucleotide-polymorphism haplotype and log [tIgE] (P=.006). There was no difference in AOAH expression levels by AOAH genotype for any of the markers. Comparing genotypic distributions at both the AOAH marker rs2727831 and CD14(-260)C>T raises the possibility of gene-gene interaction (P=.006-.036). CONCLUSION: Our results indicate that polymorphisms in markers within the AOAH gene are associated with risk of asthma and associated quantitative traits (IgE and cytokine levels) among asthmatic subjects and their families in Barbados, and there is an interactive effect on tIgE and asthma concentrations between an AOAH marker and the functional CD14(-260)C>T polymorphism. CLINICAL IMPLICATIONS: AOAH is a novel innate immunity candidate gene associated with asthma and related phenotypes in an African ancestry population.

Quantitative assessment of hard surface disinfectant activity against the foodborne pathogen Listeria monocytogenes.

Listeria monocytogenes is an important foodborne pathogen that must be controlled to ensure food safety. For the years 2003 and 2004, L. monocytogenes caused 20 deaths per 100 listeriosis cases and was responsible for most food recalls for pathogen contamination. The objective of this work was to develop a quantitative method to assess disinfectant activity against L. monocytogenes. Standard procedures for testing disinfectants against 3 bacteria are described in the AOAC Official Methods of Analysis as use-dilution methods. No standard methods are provided for L. monocytogenes. In this study, preliminary efficacy of a quaternary ammonium compound with hydroperoxide ion was determined for 25 bacterial strains. The zones of inhibition ranged from 7.0 to 12.5 mm, and the minimum inhibitory concentration ranged from 5 to 250 ppm. For final efficacy, stainless steel carriers were contaminated with L. monocytogenes and tested separately for 5, 10, and 15 min in disinfectant or phenol. After exposure, the carriers were placed into 2 series of D/E neutralization broth. For 3 replications with duplicate samples, the phenol coefficient was 3.3. This research presents a technique-sensitive method that provides quantitative data for comparison and analysis of disinfectant activity against L. monocytogenes.

Evaluation of the CD14/-260 polymorphism and house dust endotoxin exposure in the Barbados Asthma Genetics Study.

BACKGROUND: Both a functional promoter polymorphism in the gene encoding CD14 (C-260T) and exposure to endotoxin are believed to play key roles in modulating the immune response and expression of atopic disease. OBJECTIVE: We aimed to evaluate the role of the CD14 C-260T polymorphism in a population of African descent and to test for interaction between this genotype and house dust endotoxin (HDE) exposure on atopic phenotypes. METHODS: Asthmatic probands and their families were recruited as part of the Barbados Asthma Genetics Study. The C-260T polymorphism and two additional CD14 promoter markers (G-1461T, C-1721T) were genotyped. Endotoxin was measured in house dust samples. RESULTS: Using a Family-Based Association Test, the C-260T allele appeared to be protective against asthma ( z = -2.444; P = .015) and asthma severity ( z = -2.615; P = .009) under a recessive model. No significant associations were observed for the G-1461T and C-1721T markers both individually and in haplotypes. In a case-control analysis, the CD14 TT genotype was found to reduce risk of asthma compared with the CD14 CC/CT genotypes (odds ratio [OR], 0.26; 95% CI, 0.14-0.49) and was associated with lower asthma severity scores ( P < .002). The TT genotype might protect against asthma for individuals with low HDE (OR, 0.09; 95% CI, 0.03-0.24), but may be a risk factor for individuals with high HDE (OR, 11.66; 95% CI, 1.03-131.7), suggesting a gene-environment interaction. CONCLUSION: These data suggest that the CD14-260 polymorphism may play a role in controlling risk to atopic disease and underscore the importance of incorporating key environmental exposures into studies of genetic risk factors.

Evaluation of the CD14/-260 polymorphism and house dust entotoxin exposure in the Barbados Asthma Genetics Study

BACKGROUND: Both a functional promoter polymorphism in the gene encoding CD14 (C-260T) and exposure to endotoxin are believed to play key roles in modulating the immune response and expression of atopic disease. OBJECTIVE: We aimed to evaluate the role of the CD14 C-260T polymorphism in a population of African descent and to test for interaction between this genotype and house dust endotoxin (HDE) exposure on atopic phenotypes. METHODS: Asthmatic probands and their families were recruited as part of the Barbados Asthma Genetics Study. The C-260T polymorphism and two additional CD14 promoter markers (G-1461T, C-1721T) were genotyped. Endotoxin was measured in house dust samples. RESULTS: Using a Family-Based Association Test, the C-260T allele appeared to be protective against asthma (z=−2.444; P=.015) and asthma severity (z=−2.615; P=.009) under a recessive model. No significant associations were observed for the G-1461T and C-1721T markers both individually and in haplotypes. In a case-control analysis, the CD14 TT genotype was found to reduce risk of asthma compared with the CD14 CC/CT genotypes (odds ratio [OR], 0.26; 95% CI, 0.14-0.49) and was associated with lower asthma severity scores (P < .002). The TT genotype might protect against asthma for individuals with low HDE (OR, 0.09; 95% CI, 0.03-0.24), but may be a risk factor for individuals with high HDE (OR, 11.66; 95% CI, 1.03-131.7), suggesting a gene-environment interaction. CONCLUSION: These data suggest that the CD14-260 polymorphism may play a role in controlling risk to atopic disease and underscore the importance of incorporating key environmental exposures into studies of genetic risk factors.

Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung injury.

Although the pathogenic and genetic basis of acute lung injury (ALI) remains incompletely understood, the identification of novel ALI biomarkers holds promise for unique insights. Expression profiling in animal models of ALI (canine and murine) and human ALI detected significant expression of pre-B-cell colony-enhancing factor (PBEF), a gene not previously associated with lung pathophysiology. These results were validated by real-time polymerase chain reaction and immunohistochemistry studies, with PBEF protein levels significantly increased in both bronchoalveolar lavage fluid and serum of ALI models and in cytokine- or cyclic stretch-activated lung microvascular endothelium. We genotyped two PBEF single-nucleotide polymorphisms (SNPs) in a well characterized sample of white patients with sepsis-associated ALI, patients with severe sepsis, and healthy subjects and observed that carriers of the haplotype GC from SNPs T-1001G and C-1543T had a 7.7-fold higher risk of ALI (95% confidence interval 3.01-19.75, p < 0.001). The T variant from the SNP C-1543T resulted in a significant decrease in the transcription rate (1.8-fold; p < 0.01) by the reporter gene assay. Together, these results strongly indicate that PBEF is a potential novel biomarker in ALI and demonstrate the successful application of robust genomic technologies in the identification of candidate genes in complex lung disease.

Importance sampling method of correction for multiple testing in affected sib-pair linkage analysis.

Using the Genetic Analysis Workshop 13 simulated data set, we compared the technique of importance sampling to several other methods designed to adjust p-values for multiple testing: the Bonferroni correction, the method proposed by Feingold et al., and naïve Monte Carlo simulation. We performed affected sib-pair linkage analysis for each of the 100 replicates for each of five binary traits and adjusted the derived p-values using each of the correction methods. The type I error rates for each correction method and the ability of each of the methods to detect loci known to influence trait values were compared. All of the methods considered were conservative with respect to type I error, especially the Bonferroni method. The ability of these methods to detect trait loci was also low. However, this may be partially due to a limitation inherent in our binary trait definitions.