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1.  Upper Respiratory Tract Microbial Communities, Acute Otitis Media Pathogens, and Antibiotic Use in Healthy and Sick Children 
Applied and Environmental Microbiology  2012;78(17):6262-6270.
The composition of the upper respiratory tract microbial community may influence the risk for colonization by the acute otitis media (AOM) pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. We used culture-independent methods to describe upper respiratory tract microbial communities in healthy children and children with upper respiratory tract infection with and without concurrent AOM. Nasal swabs and data were collected in a cross-sectional study of 240 children between 6 months and 3 years of age. Swabs were cultured for S. pneumoniae, and real-time PCR was used to identify S. pneumoniae, H. influenzae, and M. catarrhalis. The V1-V2 16S rRNA gene regions were sequenced using 454 pyrosequencing. Microbial communities were described using a taxon-based approach. Colonization by S. pneumoniae, H. influenzae, and M. catarrhalis was associated with lower levels of diversity in upper respiratory tract flora. We identified commensal taxa that were negatively associated with colonization by each AOM bacterial pathogen and with AOM. The balance of these relationships differed according to the colonizing AOM pathogen and history of antibiotic use. Children with antibiotic use in the past 6 months and a greater abundance of taxa, including Lactococcus and Propionibacterium, were less likely to have AOM than healthy children (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25 to 0.85). Children with no antibiotic use in the past 6 months, a low abundance of Streptococcus and Haemophilus, and a high abundance of Corynebacterium and Dolosigranulum were less likely to have AOM (OR, 0.51; 95% CI, 0.31 to 0.83). An increased understanding of polymicrobial interactions will facilitate the development of effective AOM prevention strategies.
doi:10.1128/AEM.01051-12
PMCID: PMC3416608  PMID: 22752171
2.  Stigma Mediates the Relationship Between Self-Efficacy, Medication Adherence, and Quality of Life Among People Living with HIV/AIDS in China 
AIDS Patient Care and STDs  2011;25(11):665-671.
Abstract
Although the relationship between self-efficacy and health-related behaviors is well known, limited data are available describing the association between self-efficacy and HIV stigma. Specifically, it is not known if the relationship between self-efficacy and health outcomes is mediated by HIV stigma. This study aimed to test these relationships. Data were collected from 202 HIV/AIDS patients in China using questionnaires measuring self-efficacy for disease management, self-reported 7 day medication adherence, perceived HIV/AIDS stigma and quality of life. The total mean score for self-efficacy was 6.73 (range, 2.78–10.0), and the total mean score for HIV stigma was 102.24 (range, 57.0–148.0). Seventy-four percent (150/202) of subjects reported missing no medication doses during past 7 days, and 73% (148/202) subjects reported a quality of life score over 60. There was a moderate level of association between self-efficacy and HIV stigma (Pearson r=-0.43, p=0.000). High self-efficacy predicted better medication adherence (odds ratio [OR]=1.82, 95% confidence interval [CI]=1.40–2.36) and better quality of life (OR=1.28, 95% CI=1.03–1.60) after controlling for demographic and HIV related characteristics. HIV stigma partially mediated the relationship between self-efficacy and medication adherence (OR=1.64, 95% CI=1.26-2.15; Sobel test result Z=1.975, p=0.048). HIV stigma totally mediated the relationship between self-efficacy and quality of life (OR=1.15, 95% CI=0.91–1.46; Sobel test result Z=2.362, p=0.018). The results suggest that, although self-efficacy is an important predictor for medication adherence and quality of life, HIV stigma as a mediator should not be neglected. Health care providers should also evaluate HIV stigma conditions when seeking to improve self-efficacy through interventions.
doi:10.1089/apc.2011.0174
PMCID: PMC3279711  PMID: 22023316
3.  Unnecessary Arrhythmia Monitoring and Underutilization of Ischemia and QT Interval Monitoring in Current Clinical Practice: Baseline Results of the Practical Use of the Latest Standards for Electrocardiography (PULSE) Trial 
Journal of electrocardiology  2010;43(6):542-547.
Purpose
To examine the appropriate use of arrhythmia, ischemia, and QTc interval monitoring in the acute care setting.
Methods
We analyzed baseline data of the PULSE Trial, a multi-site randomized clinical trial evaluating the effect of implementing ECG monitoring practice standards. Research nurses reviewed medical records for indications for monitoring and observed if arrhythmia, ischemia, and QT interval monitoring were being done on 1,816 patients in 17 hospitals.
Results
Almost all (99%) patients with an indication for arrhythmia monitoring were being monitored, but 85% of patients with no indication were monitored. Of patients with an indication for ischemia monitoring, 35% were being monitored, but 26% with no indication were being monitored for ST-segment changes. Only 21% of patients with an indication for QT interval monitoring had a QTc documented, but 18% of patients with no indication had a QTc documented.
Conclusion
Our data show evidence of inappropriate monitoring: under-monitoring for ischemia and QTc prolongation and over-monitoring for all 3 types of monitoring, especially arrhythmia monitoring.
doi:10.1016/j.jelectrocard.2010.07.018
PMCID: PMC2970641  PMID: 20832819
4.  An Analysis of Electronically Monitored Adherence to Antiretroviral Medications 
AIDS and behavior  2008;14(4):755-768.
Medication adherence studies increasingly collect data electronically, often using Medication Event Monitoring System (MEMS) caps. Analyses typically focus on summary adherence measures, although more complete analyses are possible using adaptive statistical methods. These methods were used to describe individual-subject adherence patterns for MEMS data from a clinical trial. Subjects were adaptively clustered into groups with similar adherence patterns and clusters were compared on a variety of subject characteristics. There were seven different adherence clusters: consistently high, consistently moderately high, consistently moderate, consistently moderately low, consistently low, deteriorating starting early, and deteriorating late. Compared to other subjects, subjects with consistently high and consistently moderately high adherence were more likely to be male, White, and older and to maintain during study participation a CD4 cell count over 500 and an HIV viral load of at most 400 copies/ml. These results demonstrate the effectiveness of adaptive methods for comprehensive analysis of MEMS data.
doi:10.1007/s10461-008-9512-z
PMCID: PMC3155184  PMID: 19107587
Adaptive statistical methods; antiretroviral adherence; electronic monitoring; MEMS caps
5.  Streptococcus pneumoniae Clonal Complex 199: Genetic Diversity and Tissue-Specific Virulence 
PLoS ONE  2011;6(4):e18649.
Streptococcus pneumoniae is an important cause of otitis media and invasive disease. Since introduction of the heptavalent pneumococcal conjugate vaccine, there has been an increase in replacement disease due to serotype 19A clonal complex (CC)199 isolates. The goals of this study were to 1) describe genetic diversity among nineteen CC199 isolates from carriage, middle ear, blood, and cerebrospinal fluid, 2) compare CC199 19A (n = 3) and 15B/C (n = 2) isolates in the chinchilla model for pneumococcal disease, and 3) identify accessory genes associated with tissue-specific disease among a larger collection of S. pneumoniae isolates. CC199 isolates were analyzed by comparative genome hybridization. One hundred and twenty-seven genes were variably present. The CC199 phylogeny split into two main clades, one comprised predominantly of carriage isolates and another of disease isolates. Ability to colonize and cause disease did not differ by serotype in the chinchilla model. However, isolates from the disease clade were associated with faster time to bacteremia compared to carriage clade isolates. One 19A isolate exhibited hypervirulence. Twelve tissue-specific genes/regions were identified by correspondence analysis. After screening a diverse collection of 326 isolates, spr0282 was associated with carriage. Four genes/regions, SP0163, SP0463, SPN05002 and RD8a were associated with middle ear isolates. SPN05002 also associated with blood and CSF, while RD8a associated with blood isolates. The hypervirulent isolate's genome was sequenced using the Solexa paired-end sequencing platform and compared to that of a reference serotype 19A isolate, revealing the presence of a novel 20 kb region with sequence similarity to bacteriophage genes. Genetic factors other than serotype may modulate virulence potential in CC199. These studies have implications for the long-term effectiveness of conjugate vaccines. Ideally, future vaccines would target common proteins to effectively reduce carriage and disease in the vaccinated population.
doi:10.1371/journal.pone.0018649
PMCID: PMC3077395  PMID: 21533186
6.  Microbial Communities of the Upper Respiratory Tract and Otitis Media in Children 
mBio  2011;2(1):e00245-10.
Streptococcus pneumoniae asymptomatically colonizes the upper respiratory tract of children and is a frequent cause of otitis media. Patterns of microbial colonization likely influence S. pneumoniae colonization and otitis media susceptibility. This study compared microbial communities in children with and without otitis media. Nasal swabs and clinical and demographic data were collected in a cross-sectional study of Philadelphia, PA, children (6 to 78 months) (n = 108) during the 2008-2009 winter respiratory virus season. Swabs were cultured for S. pneumoniae. DNA was extracted from the swabs; 16S rRNA gene hypervariable regions (V1 and V2) were PCR amplified and sequenced by Roche/454 Life Sciences pyrosequencing. Microbial communities were described using the Shannon diversity and evenness indices. Principal component analysis (PCA) was used to group microbial community taxa into four factors representing correlated taxa. Of 108 children, 47 (44%) were colonized by S. pneumoniae, and 25 (23%) were diagnosed with otitis media. Microbial communities with S. pneumoniae were significantly less diverse and less even. Two PCA factors were associated with a decreased risk of pneumococcal colonization and otitis media, as follows: one factor included potentially protective flora (Corynebacterium and Dolosigranulum), and the other factor included Propionibacterium, Lactococcus, and Staphylococcus. The remaining two PCA factors were associated with an increased risk of otitis media. One factor included Haemophilus, and the final factor included Actinomyces, Rothia, Neisseria, and Veillonella. Generally, these taxa are not considered otitis media pathogens but may be important in the causal pathway. Increased understanding of upper respiratory tract microbial communities will contribute to the development of otitis media treatment and prevention strategies.
IMPORTANCE
Otitis media (middle ear infection) is the most common reason for pediatric sick visits in the United States. Streptococcus pneumoniae is a leading otitis media pathogen. S. pneumoniae must colonize the upper respiratory tract and compete with a complex community of nonpathogenic bacteria before infecting the middle ear. We compared microbial communities in the upper respiratory tract of children who had otitis media and those who did not. Members of the normal flora, i.e., Corynebacterium and Dolosigranulum, were protective for S. pneumoniae colonization and otitis media. As expected, the genera Haemophilus was associated with otitis media. Surprisingly, Actinomyces, Rothia, Neisseria, and Veillonella were associated with an increased risk of otitis media. These bacteria are not otitis media pathogens but may be associated with antibiotic use or involved in the causal pathway to disease. Increased understanding of upper respiratory tract microbial communities will lead to new ways to prevent middle ear infections, including probiotics.
doi:10.1128/mBio.00245-10
PMCID: PMC3031303  PMID: 21285435
7.  Variation in the Presence of Neuraminidase Genes among Streptococcus pneumoniae Isolates with Identical Sequence Types  
Infection and Immunity  2006;74(6):3360-3365.
Streptococcus pneumoniae frequently colonizes the upper respiratory tract of young children and is an important cause of otitis media and invasive disease. Carriage is more common than disease, yet the genetic factors that predispose a given clone for disease are not known. The relationship between capsule type, genetic background, and virulence is complex, and important questions remain regarding how pneumococcal clones differ in their ability to cause disease. Pneumococcal neuraminidase cleaves sialic acid-containing substrates and is thought to be important for pneumococcal virulence. We describe the distribution of multilocus sequence types (ST), capsule type, and neuraminidase genes among 342 carriage, middle ear, blood, and cerebrospinal fluid (CSF) pneumococcal strains from young children. We found 149 STs among our S. pneumoniae isolates. nanA was present in all strains, while nanB and nanC were present in 96% and 51% of isolates, respectively. The distribution of nanC varied among the strain collections from different tissue sources (P = 0.03). The prevalence of nanC was 1.41 (95% confidence interval, 1.11, 1.79) times higher among CSF isolates than among carriage isolates. We identified isolates of the same ST that differed in the presence of nanB and nanC. These studies demonstrate that virulence determinants, other than capsule loci, vary among strains of identical ST. Our studies suggest that the presence of nanC may be important for tissue-specific virulence. Studies that both incorporate MLST and take into account additional virulence determinants will provide a greater understanding of the pneumococcal virulence potential.
doi:10.1128/IAI.01442-05
PMCID: PMC1479257  PMID: 16714565
8.  Genomic Subtraction Followed by Dot Blot Screening of Streptococcus pneumoniae Clinical and Carriage Isolates Identifies Genetic Differences Associated with Strains That Cause Otitis Media  
Infection and Immunity  2005;73(5):2805-2811.
Streptococcus pneumoniae strains are the leading cause of bacterial otitis media, yet little is known about specific bacterial factors important for this disease. We utilized a molecular epidemiological approach involving genomic subtraction of the S. pneumoniae serogroup 19 middle ear strain 5093 against the laboratory strain R6. Resulting subtraction PCR (sPCR) products were used to screen a panel of 93 middle ear, 90 blood, 35 carriage, and 58 cerebrospinal fluid isolates from young children to identify genes found more frequently among middle ear isolates. Probe P41, similar to a hypothetical protein of Brucella melitensis, occurred among 41% of middle ear isolates and was found 2.8 (95% confidence interval [CI], 1.32 to 6.5), 3.3 (95% CI, 1.9 to 5.7), and 1.8 (95% CI, 1.1 to 3.0) times more frequently among middle ear strains than carriage, blood, or meningitis strains, respectively. sPCR fragment H10, similar to an unknown Streptococcus agalactiae protein, was present in 31% of middle ear isolates and occurred 3.6 (95% CI, 1.2 to 11.2), 2.8 (95% CI, 1.5 to 5.4), and 2.6 (95% CI, 1.2 to 5.5) times more often among middle ear isolates than carriage, blood, or meningitis strains, respectively. These studies have identified two genes of potential importance in otitis media virulence. Further studies are warranted to outline the precise role of these genes in otitis media pathogenesis.
doi:10.1128/IAI.73.5.2805-2811.2005
PMCID: PMC1087362  PMID: 15845484
9.  HIV as a chronic disease: Implications for long-term care at an AIDS-dedicated skilled nursing facility 
Objective
To describe the characteristics and outcomes of the first 3 years of admissions to a dedicated skilled nursing facility for people with acquired immunodeficiency syndrome (AIDS).
Methods
Systematic chart review of consecutive admissions to a 30-bed, AIDS-designated long-term care facility in New Haven, Connecticut, from October 1995 through December 1998.
Results
The facility has remained filled to 90% or more of its bed capacity since opening. Of 180 patients (representing 222 admissions), 69% were male; mean age was 41 years; 57% were injection drug users; 71% were admitted directly from a hospital. Leading reasons for admission were (1) the need for 24-hour nursing/medical supervision, (2) completion of acute medical treatment, and (3) terminal care. On admission, the median Karnofsky score was 40, and median CD4+ cell count was 24/mm3; 48% were diagnosed with serious neurologic disease, 44% with psychiatric illness; patients were receiving a median of 11 medications on admission. Of 202 completed admissions, 44% of patients died, 48% were discharged to the community, 8% were discharged to a hospital. Median length of stay was 59 days (range 1 to 1,353). Early (≤6 months) mortality was predicted by lower admission CD4+ count, impairments in activities of daily living, and the absence of a psychiatric history; long-term stay (>6 months) was predicted by total number of admission medications, neurologic disease, and dementia. Comparison of admissions from 1995 to 1996 to those in 1997 to 1998 indicated significantly decreased mortality rates and increased prevalence of psychiatric illness between the two periods (P<.01).
Conclusions
A dedicated skilled nursing facility for people with AIDS can fill an important service need for patients with advanced disease, acute convalescence, long-term care, and terminal care. The need for long-term care may continue to grow for patients who do not respond fully to current antiretroviral therapies and/or have significant neuropsychiatric comorbidities. This level of care may be increasingly important not only in reducing lengths of stay in the hospital, but also as a bridge to community-based residential options in the emerging chronic disease phase of the AIDS epidemic.
doi:10.1007/BF02390530
PMCID: PMC3456125  PMID: 10856000
AIDS; End-of-Life Care; Health Services; Long-Term Care; Palliative Care; Skilled Nursing Facilities

Results 1-9 (9)