Does discovery of differentially culturable M tuberculosis really demand a new treatment paradigm? Longitudinal analysis of DNA clearance from sputum.

BACKGROUND: According to the traditional tuberculosis (TB) treatment paradigm, the initial doses of treatment rapidly kill most Mycobacterium tuberculosis (Mtb) bacilli in sputum, yet many more months of daily treatment are required to eliminate a small, residual subpopulation of drug-tolerant bacilli. This paradigm has recently been challenged following the discovery that up to 90% of Mtb bacilli in sputum are culturable only with growth-factor supplementation. These "differentially culturable" bacilli are hypothesized to be more drug-tolerant than routinely culturable bacilli. This hypothesis implies an alternative paradigm in which TB treatment does not rapidly reduce the total Mtb population but only the small, routinely culturable subpopulation. To evaluate these competing paradigms, we developed a culture-independent method for quantifying the viable fraction of Mtb bacilli in sputum during treatment. METHODS: We used GeneXpert MTB/RIF to quantify Mtb DNA in sputa collected longitudinally from Ugandan adults taking standard 4-drug treatment for drug-susceptible pulmonary TB. We modeled GeneXpert cycle thresholds over time using nonlinear mixed-effects regression. We adjusted these models for clearance of DNA from killed-but-not-yet-degraded bacilli, assuming clearance half-lives ranging from 0 to 1.25 days. We used a convolution integral to quantify DNA from viable bacilli only, and converted cycle thresholds to Mtb genomic equivalents. We replicated our results in a South African cohort. RESULTS: We enrolled 41 TB patients in Uganda. Assuming a DNA-clearance half-life of 0 days, genomic equivalents of viable sputum bacilli decreased by 0.22 log/day until 8.8 days, then by 0.07 log/day afterwards. Assuming a DNA-clearance half-life of 1.25 days, genomic equivalents of viable bacilli decreased by 0.36 log/day until 5.0 days, then by 0.06 log/day afterwards. By day 7, viable Mtb had decreased by 97.2-98.8%. We found similar results for 19 TB patients in South Africa. DISCUSSION: Using a culture-independent method, we found that TB treatment rapidly eliminates most viable Mtb in sputum. These findings are incompatible with the hypothesis that differentially culturable bacilli are drug-tolerant. CONCLUSIONS: A culture-independent method for measuring viable Mtb in sputum during treatment corroborates the traditional TB treatment paradigm in which a rapid bactericidal phase precedes slow, elimination of a small, residual bacillary subpopulation.

The interaction between rural/urban status and dual use status among veterans with heart failure.

INTRODUCTION: Dual healthcare system use is associated with higher rates of healthcare utilization, but the influence of rurality on this phenomenon is unclear. This study aimed to determine the extent to which rurality in the USA modifies the likelihood for acute healthcare use among veterans with heart failure (HF). METHODS: Using merged Veterans Affairs (VA), Medicare, and state-level administrative data, a retrospective cohort study of 4985 veterans with HF was performed. Negative binomial regression with interaction term for dual use and geographic location was used to estimate and compare the associations between dual use (as compared to VA-only use) and emergency department (ED) visits, hospitalizations, and 30-day hospital readmissions in rural/highly rural veterans versus urban veterans. RESULTS: The association between dual use compared to VA-only use and ED visits was stronger in rural/highly rural veterans (RR=1.28 (95%CI: 1.21,1.35)) than in urban veterans (rate ratio (RR)=1.17 (95% confidence interval (CI): 1.11,1.22)) (interaction p-value=0.0109), while the association between dual use and all-cause hospitalizations was similar in rural/highly rural veterans (RR=2.00 (95%CI: 1.87, 2.14)) and in urban veterans (RR=1.87 (95%CI: 1.77,1.98)). The association between dual use and all-cause 30-day hospital readmission was also similar in rural/highly rural versus urban veterans. CONCLUSION: Rurality significantly modifies the likelihood of ED visits for HF, although this effect was not observed for hospitalizations or hospital readmissions. While other patient- or system-level factors may more heavily influence hospitalization and readmission in this population, dual use appears to be a marker for higher healthcare utilization and worse outcomes for both urban and rural veterans.

Dual health care system use is associated with higher rates of hospitalization and hospital readmission among veterans with heart failure.

BACKGROUND: Heart failure (HF) frequently causes hospital admission and readmission. Patients receiving care from multiple providers and facilities (dual users) may risk higher health care utilization and worse health outcomes. METHODS: To determine rates of emergency department (ED) visits, hospitalizations, and hospital readmissions relative to dual use among HF patients, we analyzed a retrospective cohort of 13,977 veterans with HF hospitalized at the Veterans Affairs (VA) or non-VA facilities from 2007 to 2011; we analyzed rates of acute health care utilization using zero-inflated negative binomial regression. RESULTS: Compared to VA-only users and dual users, individuals receiving all of their ED and hospital care outside the VA tended to be older, more likely to be non-Hispanic white and married, and less likely to have high levels of service connected disability. Compared to VA-only users, dual users had significantly higher rates of ED visits for HF as a primary diagnosis (adjusted rate ratio 1.15, 95% CI 1.04-1.27), hospitalization for HF (adjusted rate ratio 1.4, 95% CI 1.26-1.56), hospital readmission after HF hospitalization (all cause) (1.46, 95% CI 1.30-1.65), and HF-specific hospital readmission after HF hospitalization (1.46, 95% CI 1.31-1.63). With the exception of hospitalization for any primary diagnosis, non-VA-only users had significantly lower rates of ED visits, hospitalization, and readmission compared to VA-only users. CONCLUSIONS: Dual use is associated with higher rates of health care utilization among patients with HF. Interventions should be devised to encourage continuity of care where possible and to improve the effectiveness and safety of dual use in instances where it is necessary or desired.

Tuberculosis progression rates in U.S. Immigrants following screening with interferon-gamma release assays.

BACKGROUND: Interferon-gamma release assays may be used as an alternative to the tuberculin skin test for detection of M. tuberculosis infection. However, the risk of active tuberculosis disease following screening using interferon-gamma release assays in immigrants is not well defined. To address these uncertainties, we determined the incidence rates of active tuberculosis disease in a cohort of high-risk immigrants with Class B TB screened with interferon-gamma release assays (IGRAs) upon arrival in the United States. METHODS: Using a retrospective cohort design, we enrolled recent U.S. immigrants with Class B TB who were screened with an IGRA (QuantiFERON ® Gold or Gold In-Tube Assay) at the San Francisco Department of Public Health Tuberculosis Control Clinic from January 2005 through December 2010. We reviewed records from the Tuberculosis Control Patient Management Database and from the California Department of Public Health Tuberculosis Case Registry to determine incident cases of active tuberculosis disease through February 2015. RESULTS: Of 1233 eligible immigrants with IGRA screening at baseline, 81 (6.6 %) were diagnosed with active tuberculosis disease as a result of their initial evaluation. Of the remaining 1152 participants without active tuberculosis disease at baseline, 513 tested IGRA-positive and 639 tested IGRA-negative. Seven participants developed incident active tuberculosis disease over 7730 person-years of follow-up, for an incidence rate of 91 per 100,000 person-years (95 % CI 43-190). Five IGRA-positive and two IGRA-negative participants developed active tuberculosis disease (incidence rates 139 per 100,000 person-years (95 % CI 58-335) and 48 per 100,000 person-years (95 % CI 12-193), respectively) for an unadjusted incidence rate ratio of 2.9 (95 % CI 0.5-30, p = 0.21). IGRA test results had a negative predictive value of 99.7 % but a positive predictive value of only 0.97 %. CONCLUSIONS: Among high-risk immigrants without active tuberculosis disease at the time of entry into the United States, risk of progression to active tuberculosis disease was higher in IGRA-positive participants compared with IGRA-negative participants. However, these findings did not reach statistical significance, and a positive IGRA at enrollment had a poor predictive value for progressing to active tuberculosis disease. Additional research is needed to identify biomarkers and develop clinical algorithms that can better predict progression to active tuberculosis disease among U.S. immigrants.

Association of DDT and heptachlor epoxide in human blood with diabetic nephropathy.

Six organochlorine pesticides and pesticide metabolites in human blood were tested to determine their relationships with diabetic nephropathy. The data were derived from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 (unweighted, n=2992, population estimate=133,088,752). The six chemicals were p,p'-DDT (dichlorodiphenyltrichloroethane), p,p'-DDE (dichlorodiphenyltrichloroethylene), beta-hexachlorocyclohexane, oxychlordane, trans-nonachlor and heptachlor epoxide. In this research, total diabetes included diagnosed and undiagnosed diabetes (glycohemoglobin, A1c ≥6.5%), and nephropathy was defined as a urinary albumin to creatinine ratio >30 mg/g, representing microalbuminuria and macroalbuminuria. The pesticide p,p'-DDT and pesticide metabolite heptachlor epoxide were significantly associated with total diabetes with nephropathy, with odds ratios of 2.08 (95% CI 1.06-4.11) and 1.75 (95% CI 1.05-2.93), respectively. Organochlorine pesticides are thought to act through the constitutive androstane receptor/pregnane X receptor disease pathway, but this is not well established. When p,p'-DDT and heptachlor epoxide were both elevated, the odds ratio for diabetic nephropathy was 2.76 (95% CI 1.31-5.81), and when six of six organochlorine pesticides and pesticide metabolites, were elevated, the odds ratio for diabetic nephropathy was 3.00 (95% CI 1.08-8.36). The differences in the odds ratios for these groups appear to be due to differences in the mean heptachlor epoxide concentration of each category. Organochlorine pesticides and pesticide metabolites are known to have estrogenic, antiestrogenic or antiandrogenic activity. The constitutive androstane receptor/pregnane X receptor pathway is thought to interact with the aryl hydrocarbon receptor pathway, and the associations noted may be due to that interaction.

Dioxins, furans and dioxin-like PCBs in human blood: causes or consequences of diabetic nephropathy?

Nephropathy, or kidney disease, is a major, potential complication of diabetes. We assessed the association of 6 chlorinated dibenzo-p-dioxins, 9 chlorinated dibenzofurans and 8 polychlorinated biphenyls (PCBs) in blood with diabetic nephropathy in the 1999-2004 National Health and Nutrition Examination Survey (unweighted N=2588, population estimate=117,658,357). Diabetes was defined as diagnosed or undiagnosed (glycohemoglobin ≥ 6.5%) and nephropathy defined as urinary albumin to creatinine ratio >30 mg/g, representing microalbuminuria or macroalbuminuria. For the 8 chemicals analyzed separately, values above the 75th percentile were considered elevated, whereas for the other 15 compounds values above the maximum limit of detection were considered elevated. Seven of 8 dioxins and dioxin-like compounds, analyzed separately, were found to be associated with diabetic nephropathy. The chemicals associated with diabetic nephropathy were: 1,2,3,6,7,8-Hexachlorodibenzo-p-dioxin; 1,2,3,4,6,7,8,9-Octachlorodibenzo-p-dioxin; 2,3,4,7,8-Pentachlorodibenzofuran; PCB 126; PCB 169; PCB 118; and PCB 156. Three of the 8 dioxins and dioxin-like compounds; 1,2,3,4,6,7,8,9-Octachlorodibenzo-p-dioxin; 2,3,4,7,8-Pentachlorodibenzofuran and PCB 118; expressed as log-transformed continuous variables; were associated with diabetes without nephropathy. When 4 or more of the 23 chemicals were elevated the odds ratios were 7.00 (95% CI=1.80-27.20) for diabetic nephropathy and 2.13 (95% CI=0.95-4.78) for diabetes without nephropathy. Log-transformed toxic equivalency (TEQ) was associated with both diabetic nephropathy, and diabetes without nephropathy, the odds ratios were 2.35 (95% CI=1.57-3.52) for diabetic nephropathy, and 1.44 (95% CI=1.11-1.87) for diabetes without nephropathy. As the kidneys function to remove waste products from the blood, diabetic nephropathy could be either the cause or the consequence (or both) of exposure to dioxins, furans and dioxin-like PCBs.

Associations of dioxins, furans and dioxin-like PCBs with diabetes and pre-diabetes: is the toxic equivalency approach useful?

Toxic equivalency factors for dioxins and dioxin-like compounds have been established by the World Health Organization. Toxic equivalency (TEQ) was derived using 6 chlorinated dibenzo-p-dioxins, 9 chlorinated dibenzofurans and 8 polychlorinated biphenyls, in blood, from the 1999-2004 National Health and Nutrition Examination Survey. Relationships of 8 individual chemicals, the number of compounds elevated, and TEQ with pre-diabetes and total diabetes (diagnosed and undiagnosed) were investigated using logistic regressions. For the 8 chemicals analyzed separately, values above the 75th percentile were considered elevated, whereas for the other 15 compounds, values above the maximum limit of detection were considered elevated. Pre-diabetes with glycohemoglobin (A1c) 5.9-6.4% was associated with PCB 126, PCB 118 and having one or more compounds elevated (odds ratio 2.47, 95% CI 1.51-4.06). Pre-diabetes with A1c 5.7-5.8% was not associated with any individual chemical or the number of compounds elevated. Total diabetes was associated with 6 of the 8 individual compounds tested, and was associated with having 4 or more compounds elevated. Toxic equivalency ≥81.58 TEQ fg/g was associated with total diabetes (odds ratio 3.08, 95% CI 1.20-7.90), but was not associated with A1c 5.9-6.4%. Having multiple compounds elevated appeared to be important for total diabetes, whereas for pre-diabetes with A1c 5.9-6.4%, having a single compound elevated appeared most important. Diabetes plus A1c ≥5.9% was associated with 34.16-81.57 TEQ fg/g (odds ratio 2.00, 95% CI 1.06-3.77) and with ≥81.58 TEQ fg/g (odds ratio 2.48, 95% CI 1.21-5.11), indicating that half the population has elevated risk for this combination of conditions.

Interferon-γ release assays for active pulmonary tuberculosis diagnosis in adults in low- and middle-income countries: systematic review and meta-analysis.

BACKGROUND: The diagnostic value of interferon-γ release assays (IGRAs) for active tuberculosis in low- and middle-income countries is unclear. METHODS: We searched multiple databases for studies published through May 2010 that evaluated the diagnostic performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB (T-SPOT) among adults with suspected active pulmonary tuberculosis or patients with confirmed cases in low- and middle-income countries. We summarized test performance characteristics with use of forest plots, hierarchical summary receiver operating characteristic (HSROC) curves, and bivariate random effects models. RESULTS: Our search identified 789 citations, of which 27 observational studies (17 QFT-GIT and 10 T-SPOT) evaluating 590 human immunodeficiency virus (HIV)-uninfected and 844 HIV-infected individuals met inclusion criteria. Among HIV-infected patients, HSROC/bivariate pooled sensitivity estimates (highest quality data) were 76% (95% confidence interval [CI], 45%-92%) for T-SPOT and 60% (95% CI, 34%-82%) for QFT-GIT. HSROC/bivariate pooled specificity estimates were low for both IGRA platforms among all participants (T-SPOT, 61% [95% CI, 40%-79%]; QFT-GIT, 52% [95% CI, 41%-62%]) and among HIV-infected persons (T-SPOT, 52% [95% CI, 40%-63%]; QFT-GIT, 50% [95% CI, 35%-65%]). There was no consistent evidence that either IGRA was more sensitive than the tuberculin skin test for active tuberculosis diagnosis. CONCLUSIONS: In low- and middle-income countries, neither the tuberculin skin test nor IGRAs have value for active tuberculosis diagnosis in adults, especially in the context of HIV coinfection.

IRon Overload screeNing tool (IRON): development of a tool to guide screening in primary care.

Iron overload is associated with significant morbidity and mortality yet is easily treated. The objective of this study was to create a tool that could be easily adapted to clinical practice that indicates the likelihood of a patient having undetected iron overload. We used the National Health and Nutrition Examination Survey (NHANES) 1999-2002 for US adults aged 20 years and older to build a model (unweighted n=8,779). We chose potential variables for inclusion that could be gathered by self-report or measured without laboratory data and were suggested by past literature on hemochromatosis and iron overload. We computed logistic regressions to create the scores by initially evaluating the variables' relationship with elevated ferritin and elevated transferrin saturation and then using odds ratios to correspond to scores. The resulting score on the IRon Overload ScreeNing Tool (IRON) was then validated with data on 13,844 adults in the NHANES III, 1988-94. Predictors in the final tool were age, gender, previous diagnoses of liver condition, osteoporosis or thyroid disease. The IRON score yielded an area under the curve (AUC) in the NHANES 1999-02 of 0.720 and an AUC of 0.685 in the NHANES III validation sample. The IRON score is a tool to assist in identification of patients with iron overload that has several qualities that make it attractive for use in clinical practice with an undifferentiated patient population including brevity, easily collected information and predictive ability comparable to other tools that help in directing screening.

Tea and coffee consumption and MRSA nasal carriage.

PURPOSE: Hot tea and coffee have been found to have antimicrobial properties. The purpose of this study was to determine whether the consumption of tea, coffee, or both is associated with less frequent nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA). METHODS: We performed a secondary analysis of data from the 2003-2004 National Health and Nutrition Examination Survey to investigate the relationship between the consumption of coffee, hot tea, cold tea, and soft drinks, and MRSA nasal carriage among the noninstitutionalized population of the United States. RESULTS: An estimated 2.5 million persons (1.4% of the population) were MRSA nasal carriers. In an adjusted logistic regression analysis controlling for age, race, sex, poverty-income ratio, current health status, hospitalization in the past 12 months, and use of antibiotics in the past month, individuals who reported consuming hot tea were one-half as likely to have MRSA nasal carriage relative to individuals who drank no hot tea (odds ratio = 0.47; 95% confidence interval, 0.31-0.71). Similarly, individuals who reported consuming coffee had about a one-half reduction in the risk of MRSA nasal carriage relative to individuals who drank no coffee (odds ratio = 0.47; 95% confidence interval, 0.24-0.93). CONCLUSIONS: Consumption of hot tea or coffee is associated with a lower likelihood of MRSA nasal carriage. Our findings raise the possibility of a promising new method to decrease MRSA nasal carriage that is safe, inexpensive, and easily accessible.

Impact of insurance and hospital ownership on hospital length of stay among patients with ambulatory care-sensitive conditions.

PURPOSE Some studies suggest proprietary (for-profit) hospitals are maximizing financial margins from patient care by limiting therapies or decreasing length of stay for uninsured patients. This study examines the role of insurance related to length of stay once the patient is in the hospital and risk for mortality, particularly in a for-profit environment. METHODS We undertook an analysis of hospitalizations in the National Hospital Discharge Survey (NHDS) of the 5-year period of 2003 to 2007 for patients aged 18 to 64 years (unweighted n = 849,866; weighted n = 90 million). The analysis included those who were hospitalized with both ambulatory care-sensitive conditions (ACSCs), hospitalizations considered to be preventable, and non-ACSCs. We analyzed the transformed mean length of stay between individuals who had Medicaid or all other insurance types while hospitalized and those who were hospitalized without insurance. This analysis was stratified by hospital ownership. We also examined the relationship between in-hospital mortality and insurance status. RESULTS After controlling for comorbidities; age, sex, and race/ethnicity; and hospitalizations with either an ACSC or non-ACSC diagnosis, patients without insurance tended to have a significantly shorter length of stay. Across all hospital types, the mean length of stay for ACSCs was significantly shorter for individuals without insurance (2.77 days) than for those with either private insurance (2.89 days, P = .04) or Medicaid (3.19, P <.01). Among hospitalizations for ACSCs, in-hospital mortality rate for individuals with either private insurance or Medicaid was not significantly different from the mortality rate for those without insurance. CONCLUSIONS Patients without insurance have shorter lengths of stay for both ACSCs and non-ACSCs. Future research should examine whether patients without insurance are being discharged prematurely.

Impact of EHR-based clinical decision support on adherence to guidelines for patients on NSAIDs: a randomized controlled trial.

PURPOSE: Electronic health records (EHRs) with clinical decision support hold promise for improving quality of care, but their impact on management of chronic conditions has been mixed. This study examined the impact of EHR-based clinical decision support on adherence to guidelines for reducing gastrointestinal complications in primary care patients on nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: This randomized controlled trial was conducted in a national network of primary care offices using an EHR and focused on patients taking traditional NSAIDs who had factors associated with a high risk for gastrointestinal complications (a history of peptic ulcer disease; concomitant use of anticoagulants, anti-platelet medications [including aspirin], or corticosteroids; or an age of 75 years or older). The offices were randomized to receive EHR-based guidelines and alerts for high-risk patients on NSAIDs, or usual care. The primary outcome was the proportion of patients who received guideline-concordant care during the 1-year study period (June 2007-June 2008), defined as having their traditional NSAID discontinued (including a switch to a lower-risk medication), having a gastroprotective medication coprescribed, or both. RESULTS: Participants included 27 offices with 119 clinicians and 5,234 high-risk patients. Intervention patients were more likely than usual care patients to receive guideline-concordant care (25.4% vs 22.4%, adjusted odds ratio = 1.19; 95% confidence interval, 1.01-1.42). For individual high-risk groups, patients on low-dose aspirin were more likely to receive guideline-concordant care with the intervention vs usual care (25.0% vs 20.8%, adjusted odds ratio = 1.30; 95% confidence interval, 1.04-1.62), but there was no significant difference for patients in other high-risk groups. CONCLUSIONS: This study showed only a small impact of EHR-based clinical decision support for high-risk patients on NSAIDs in primary care offices. These results add to the growing literature about the complexity of EHR-based clinical decision support for improving quality of care.

Leukocyte telomere length and marital status among middle-aged adults.

BACKGROUND: being unmarried is associated with worse health and increased mortality risk. Telomere length has emerged as a marker for biological ageing but it is unclear how telomere length relates to marital status. OBJECTIVE: to examine the relationship between telomere length and marital status in a sample of middle-aged adults. DESIGN AND SUBJECTS: cross-sectional analysis among 321 adults aged 40-64 years. METHODS: telomere length was measured by PCR (T/S ratio). Participants provided information on healthy lifestyle activities including smoking, alcohol use, diet, exercise, obesity as well as social support. RESULTS: participants married or living with a partner had a mean T/S ratio of 1.70 and those widowed, divorced, separated or never married had a mean T/S ratio of 1.58 in a model adjusted for age, gender and race/ethnicity (P < 0.001). When the analysis was further adjusted for diet, alcohol consumption, exercise, smoking, social support, poverty and obesity, persons married or living with a partner had a higher mean T/S ratio of 1.69 than their unmarried counterparts (1.59) (P = 0.004). CONCLUSIONS: these results indicate that unmarried individuals have shorter telomeres. This relationship between marital status and telomere length is independent of presumed benefits of marriage such as social support and a healthier lifestyle.

Relationship of polychlorinated biphenyls with type 2 diabetes and hypertension.

Diabetes and hypertension are important contributors to morbidity and mortality worldwide. Both of these conditions are caused by some combination of genetic and environmental factors which may include exposure to persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs). Studies have shown an association between elevated serum PCBs and the metabolic syndrome, insulin sensitivity and insulin secretion. Cross-sectional studies have shown associations between diabetes or hypertension and certain PCB congeners or classes, while those same studies show no association between diabetes or hypertension and several other PCB congeners. In animal and human cell studies, various PCBs and dioxins appear to alter glucose and insulin metabolism. These studies specifically show effects on the glucose transporter (GLUT-4) gene and protein; insulin-like growth factor binding protein-1 (IGFBP-1); nuclear transcription factor kappa B (NFκB); tumor necrosis factor alpha (TNF-α); and insulin production. There are a few longitudinal studies examining the association of diabetes or hypertension and PCBs with no consensus conclusion. Some longitudinal studies have found there to be an association, others have not and a gender difference has also been noted. Prospective studies are needed to determine if PCBs and other POPs contribute to development of diabetes and hypertension.

Vitamin D and methicillin-resistant Staphylococcus aureus nasal carriage.

Studies have found that vitamin D plays an important role in mediating immune function via a number of pathways, including enhancing the release of antimicrobial peptides in the skin. Given these findings, we hypothesize that low serum vitamin D levels may increase the risk of nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA). A secondary data analysis of the National Health and Nutrition Examination Survey 2001-2004 was performed to investigate the association between serum vitamin D levels and MRSA nasal carriage for the non-institutionalized population of the USA. An estimated 2.7 million persons (1.2% of the population) are MRSA nasal carriers. An estimated 63.3 million persons (28.4% of the population) are vitamin D deficient (serum vitamin D <20 ng/ml). In an adjusted logistic regression analysis controlling for age, race, gender, poverty income ratio, current health status, hospitalization in the past 12 months, and antibiotic use in the past month, individuals with vitamin D deficiency had a statistically significant increased risk of MRSA carriage of 2.04 (95% CI 1.09-3.84). Vitamin D deficiency is associated with an increased risk of MRSA nasal carriage. Further trials may be warranted to determine whether vitamin D supplementation decreases the risk of MRSA colonization.

Association of urinary polycyclic aromatic hydrocarbons and serum C-reactive protein.

The association of 9 urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) with serum C-reactive protein (CRP) was investigated using the National Health and Nutrition Examination Survey (NHANES) 2003-2004. The unweighted number of participants included was 999, which represented 139,362,776 persons in the non-institutionalized US population. In adjusted logistic regressions, two OH-PAHs, 2-hydroxyphenanthrene and 9-hydroxyfluorene, were associated with elevated CRP (>3mg/l). Logistic regressions were adjusted for age, gender, race, exercise, body mass index, smoking status, diabetes, and hypertension. 2-Hydroxyphenanthrene >148ng/g creatinine had an odds ratio of 3.17 (95% CI 1.73-5.81) compared to 2-hydroxyphenanthrene < or =48ng/g creatinine, and 9-hydroxyfluorene >749ng/g creatinine had an odds ratio of 2.28 (95% CI 1.08-4.83) compared to 9-hydroxyfluorene < or =160ng/g creatinine. Intermediate levels of 2-hydroxyphenanthrene (49-148ng/g creatinine), and 9-hydroxyfluorene (161-749ng/g creatinine) were also significantly associated with elevated CRP compared to the respective reference categories. In a combined analysis, OH-PAHs were classified as low, medium, and high. Low OH-PAH was 2-hydroxyphenanthrene < or =48ng/g creatinine and 9-hydroxyfluorene < or =160ng/g creatinine. High OH-PAH was 2-hydroxyphenanthrene >148ng/g creatinine or 9-hydroxyfluorene >749ng/g creatinine. Participants not assigned to the low or high categories were classified as having medium OH-PAH concentrations. Compared to the low OH-PAH group, high OH-PAH had an odds ratio of 3.60 (95% CI 2.01-6.46) in an adjusted logistic regression. Given that inflammation (characterized here by CRP) is an important factor in the development of atherosclerosis and cardiovascular disease, these results suggest a role for OH-PAHs in the progression of atherosclerosis.

Impact of a policy allowing for over-the-counter statins.

BACKGROUND: allowing statins to be sold without a prescription has been widely debated in Great Britain, Canada and the USA. AIMS: To examine the impact of the recent policy in Great Britain allowing patients to purchase over-the-counter (OTC) 10 mg dose of a cholesterol-lowering drug (simvastatin) on meeting the needs of individuals at moderate risk of coronary heart disease (CHD). METHODS: we undertook an analysis of adults (aged >20 years) in the nationally representative 2006 Health Survey for England (HSE, n =10 007). We evaluated the proportion of individuals using OTC statins among all adults aged 20 years and over and among individuals eligible for them according to current guidelines. RESULTS: among adults in the HSE, 44.1% met the criteria for referral to a general practitioner for CHD risk, 9.7% were eligible for OTC statins and 46.1% did not meet the eligibility for prescribed or OTC statin therapy. Less than 1% (0.7%) were taking OTC statins. The proportion of individuals using OTC statins among those eligible for them was low and comparable to that in the overall population (0.2%). Among those taking OTC statins, 71.5% were also taking prescribed lipid lowering agents. CONCLUSION: these results suggest that the aim of addressing the treatment gap among individuals at moderate risk by offering access to OTC statins has not been achieved two years after the implementation of the policy.

An electronic medical record-based intervention to improve quality of care for gastro-esophageal reflux disease (GERD) and atypical presentations of GERD.

BACKGROUND: Gastro-esophageal reflux disease (GERD) is common in primary care but is often underdiagnosed and untreated. GERD can also present with atypical symptoms like chronic cough and asthma, and physicians may be unaware of this presentation. We aimed to implement and evaluate an intervention to improve diagnosis and treatment for GERD and atypical GERD in primary care. METHOD: This was a randomised controlled trial in primary care office practice using a national network of US practices (the Medical Quality Improvement Consortium - MQIC) that share the same electronic medical record (EMR). Thirteen offices with 53 providers were randomised to the intervention of EMR-based prompts and education, and 14 offices with 66 providers were randomised to the control group totalling over 67 000 patients and examining outcomes of GERD diagnosis and appropriate treatment. RESULTS: Among patients who did not have GERD at baseline, new diagnoses of GERD increased significantly in the intervention group (3.1%) versus the control group (2.3%) (P<0.01). This remained significant after controlling for clustering with an odds of diagnosis of 1.33 (95% CI 1.13-1.56) for the intervention group. For patients with atypical symptoms, those in the intervention group had both higher odds of being diagnosed with GERD (OR 2.02, 95% CI 1.41-2.88) and of being treated for GERD (OR 1.40, 95% CI 1.08-1.83) than those in the control group. CONCLUSIONS: GERD diagnosis and treatment in primary care, particularly among patients with atypical symptoms, can be improved through the use of an EMR-based tool incorporating decision support and education. However, significant room for improvement exists in use of appropriate treatment.

Availability of antibiotics for purchase without a prescription on the internet.

PURPOSE: Reducing inappropriate use of antibiotics is key to many antibiotic resistance initiatives. Most initiatives, however, focus almost exclusively on controlling prescribing by health care clinicians and do not focus on patient self-medication. The purpose of this study was to examine antibiotics available to patients without a prescription, a phenomenon on the Internet. METHODS: We conducted an Internet search using 2 major search engines (Google and Yahoo) with the key words "purchase antibiotics without a prescription" and "online (English only)." Vendors were compared according to the classes of antibiotics available, quantity, shipping locations, and shipping time. RESULTS: We found 138 unique vendors selling antibiotics without a prescription. Of those vendors, 36.2% sold antibiotics without a prescription, and 63.8% provided an online prescription. Penicillins were available on 94.2% of the sites, macrolides on 96.4%, fluoroquinolones on 61.6%, and cephalosporins on 56.5%. Nearly all, 98.6%, ship to the United States. The mean delivery time was 8 days, with 46.1% expecting delivery in more than 7 days. Among those selling macrolides (n = 133), 93.3% would sell azithromycin in quantities consistent with more than a single course of medication. Compared with vendors that require a medical interview, vendors who sell antibiotics without a prescription were more likely to sell quantities in excess of a single course, and the antibiotics were more likely to take more than 7 days to reach the customer. CONCLUSIONS: Antibiotics are freely available for purchase on the Internet without a prescription, a phenomenon that encourages self-medication and low quality of care.