Catherine W. Gillespie

Standard Treatment Regimens for Nongonococcal Urethritis Have Similar but Declining Cure Rates: A Randomized Controlled Trial

BACKGROUND Azithromycin or doxycycline is recommended for nongonococcal urethritis (NGU); recent evidence suggests their efficacy has declined. We compared azithromycin and doxycycline in men with NGU, hypothesizing that azithromycin was more effective than doxycycline. METHODS From January 2007 to July 2011, English-speaking males ≥16 years, attending a sexually transmitted diseases clinic in Seattle, Washington, with NGU (visible urethral discharge or ≥5 polymorphonuclear leukocytes per high-power field [PMNs/HPF]) were eligible for this double-blind, parallel-group superiority trial. Participants received active azithromycin (1 g) + placebo doxycycline or active doxycycline (100 mg twice daily for 7 days) + placebo azithromycin. Urine was tested for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Ureaplasma urealyticum biovar 2 (UU-2), and Trichomonas vaginalis (TV) using nucleic acid amplification tests. Clinical cure (<5 PMNs/HPF with or without urethral symptoms and absence of discharge) and microbiologic cure (negative tests for CT, MG, and/or UU-2) were determined after 3 weeks. RESULTS Of 606 men, 304 were randomized to azithromycin and 302 to doxycycline; CT, MG, TV, and UU-2 were detected in 24%, 13%, 2%, and 23%, respectively. In modified intent-to-treat analyses, 172 of 216 (80%; 95% confidence interval [CI], 74%-85%) receiving azithromycin and 157 of 206 (76%; 95% CI, 70%-82%) receiving doxycycline experienced clinical cure (P = .40). In pathogen-specific analyses, clinical cure did not differ by arm, nor did microbiologic cure differ for CT (86% vs 90%, P = .56), MG (40% vs 30%, P = .41), or UU-2 (75% vs 70%, P = .50). No unexpected adverse events occurred. CONCLUSIONS Clinical and microbiologic cure rates for NGU were somewhat low and there was no significant difference between azithromycin and doxycycline. Mycoplasma genitalium treatment failure was extremely common. Clinical Trials Registration.NCT00358462.

Bacterial vaginosis-associated bacteria in men: association of Leptotrichia/Sneathia spp. with nongonococcal urethritis.

Background Approximately 45% of nongonococcal urethritis cases have no identified etiology. Novel bacteria recently associated with bacterial vaginosis (BV) in women may be involved. We evaluated the association of idiopathic nongonococcal urethritis and 5 newly described BV-associated bacteria (BVAB). Methods Heterosexual men 16 years or older attending a sexually transmitted disease clinic in Seattle, Washington, from May 2007 to July 2011 and negative for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, and Ureaplasma urealyticum–biovar2 were eligible. Cases had urethral discharge or 5 or more polymorphonuclear leukocytes per high-power field in urethral exudates. Controls had no urethral discharge and less than 5 polymorphonuclear leukocytes per high-power field. Urine was tested for Atopobium spp., BVAB-2, BVAB-3, Megasphaera spp., and Leptotrichia/Sneathia spp. using quantitative taxon-directed polymerase chain reaction. Results Cases (n = 157) and controls (n = 102) were of similar age, education, and income, and most were white. Leptotrichia/Sneathia spp. was significantly associated with urethritis (24/157 [15.3%] vs. 6/102 [5.9%], P = 0.03). BVAB-2 was more common in cases than in controls (7/157 [4.5%] vs. 1/102 [1.0%], P = 0.15), and BVAB-3 (n = 2) and Megasphaera spp. (n = 1) were only detected in men with urethritis, but these bacteria were found only in men who also had Leptotrichia/Sneathia spp. Atopobium spp. was not associated with urethritis. The quantity of bacteria did not differ between cases and controls. Among treated cases, doxycycline was more effective than azithromycin for clinical cure of men with Leptotrichia/Sneathia spp. (9/10 vs. 7/12, P = 0.16) and BVAB-2 (3/3 vs. 0/3, P = 0.10). Conclusions Leptotrichia/Sneathia spp. may be urethral pathogens or contribute to a pathogenic microbiota that can also include BVAB-2, BVAB-3, and Megasphaera spp. Doxycycline may be more effective than azithromycin against these newly identified bacteria.

Sports Participation and Quality of Life in Adolescents and Young Adults with Congenital Heart Disease

BACKGROUND Adolescents and young adults with congenital heart disease (CHD) are often restricted from physical activity and sports participation, which may have adverse effects. OBJECTIVES To determine the amount of physical activity, type of sports participation, and reasons for sports restrictions, and to evaluate the effect of sports participation on quality of life (QoL) in a cohort of patients with CHD. METHODS Individuals with CHD aged 13-30 years were recruited at outpatient visits or via mailings. They completed a questionnaire addressing physical activity, sports participation, sports restrictions, and QoL (Pediatric Quality of Life Inventory). We also reviewed the patients medical record. RESULTS Of the 177 patients who responded (mean age 20 years), 31% have mild CHD, 40% have moderate CHD, and 29% have severe CHD. In the cohort, 52% participate in competitive sports, 25% recreational sports, and 23% no sports. Among patients with severe CHD, 29% participate in competitive sports that would be restricted by published guidelines (36th Bethesda Conference). After controlling for age, sex, CHD severity, residual hemodynamic disease, and comorbidities, participation in competitive sports and increased frequency of physical activity are independently associated with a higher QoL (P = .003 and P = .001, respectively). In an identical model, competitive sports participation and frequency of physical activity are associated with higher maximum predicted oxygen consumption (VO2 ) (n = 40; P = .002 and .02) and slightly lower body mass index (BMI) (P = .02 and .01). All findings were similar when analyses were stratified by recruitment method. CONCLUSIONS Patients with CHD commonly participate in competitive sports, and such participation is associated with higher QoL, improved exercise capacity, and lower BMI.

Suboptimal adherence to doxycycline and treatment outcomes among men with non-gonococcal urethritis: a prospective cohort study

Objective Doxycycline, one of two recommended therapies for non-gonococcal urethritis (NGU), consists of a 7-day course of therapy (100 mg BID). Since suboptimal adherence may contribute to poor treatment outcomes, we examined the association between self-reported imperfect adherence to doxycycline and clinical and microbiologic failure among men with NGU. Methods Men aged ≥16 years with NGU attending a Seattle, WA, sexually transmitted diseases clinic were enrolled in a double-blind, parallel-group superiority trial from January 2007 to July 2011. Men were randomised to active doxycycline/placebo azithromycin or placebo doxycycline/active azithromycin. Imperfect adherence was defined as missing ≥1 dose in 7 days. Urine was tested for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), and Ureaplasma urealyticum-biovar 2 (UU-2) using nucleic acid amplification tests. Clinical failure (symptoms and ≥5 PMNs/HPF or discharge) and microbiologic failure (positive tests for CT, MG, and/or UU-2) were determined after 3 weeks. Results 184 men with NGU were randomised to active doxycycline and provided data on adherence. Baseline prevalence of CT, MG and UU-2 was 26%, 13% and 27%, respectively. 28% of men reported imperfect adherence, and this was associated with microbiologic failure among men with CT (aRR=9.33; 95% CI 1.00 to 89.2) and UU-2 (aRR=3.08; 95% CI 1.31 to 7.26) but not MG. Imperfect adherence was not significantly associated with clinical failure overall or for any specific pathogens, but it was more common among imperfectly adherent men with CT (aRR=2.63; 0.93–7.41, p=0.07). Conclusions Adherence may be important for microbiologic cure of select pathogens. Factors other than adherence should be considered for CT-negative men with persistent NGU.

Asymptomatic urethritis is common and is associated with characteristics that suggest sexually transmitted etiology

We evaluated 236 asymptomatic men for urethritis, assessed sexual behaviors, and tested urine for pathogens. Asymptomatic urethritis was present in 38 (16.1%). Of these, nearly half (42.1%) had a previously unrecognized discharge on examination; only 18.4% had a known pathogen. Correlates included black race, anal intercourse, and number of sex partners.

Efficacy of standard therapies against Ureaplasma species and persistence among men with non-gonococcal urethritis enrolled in a randomised controlled trial

Objective Ureaplasma urealyticum biovar 2 (UU-2), but not Ureaplasma parvum (UP), has been associated with non-gonococcal urethritis (NGU), but little is known about species-specific responses to standard therapies. We examined species-specific treatment outcomes and followed men with treatment failure for 9 weeks. Methods From May 2007 to July 2011, men aged ≥16 attending a sexually transmitted disease (STD) clinic in Seattle, Washington, with NGU (urethral discharge or urethral symptoms plus ≥5 polymorphonuclear leucocytes /high-powered field) enrolled in a double-blind, randomised trial. Participants received active azithromycin (1 g) + placebo doxycycline or active doxycycline (100 mg twice a day ×7 days) + placebo azithromycin. Ureaplasma were detected in culture followed by species-specific PCR. Outcomes were assessed at 3, 6 and 9 weeks. At 3 weeks, men with persistent Ureaplasma detection received ‘reverse therapy’ (eg, active doxycycline if they first received active azithromycin). At 6 weeks, persistently positive men received moxifloxacin (400 mg×7 days). Results Of 490 men, 107 (22%) and 60 (12%) were infected with UU-2 and UP, respectively, and returned at 3 weeks. Persistent detection was similar for UU-2-infected men initially treated with azithromycin or doxycycline (25% vs 31%; p=0.53), but differed somewhat for men with UP (45% vs 24%; p=0.11). At 6 weeks, 57% of UU-2-infected and 63% of UP-infected men who received both drugs had persistent detection. Failure after moxifloxacin occurred in 30% and 36%, respectively. Persistent detection of UU-2 or UP was not associated with signs/symptoms of NGU. Conclusions Persistent detection after treatment with doxycycline, azithromycin and moxifloxacin was common for UU and UP, but not associated with persistent urethritis. Trial registration number NCT00358462.

Aspirin use and knowledge in the community: a population- and health facility based survey for measuring local health system performance.

BackgroundLittle is known about the relationship between cardiovascular risk, disease and actual use of aspirin in the community.MethodsThe Measuring Disparities in Chronic Conditions (MDCC) study is a community and health facility-based survey designed to track disparities in the delivery of health interventions for common chronic diseases. MDCC includes a survey instrument designed to collect detailed information about aspirin use. In King County, WA between 2011 and 2012, we surveyed 4633 white, African American, or Hispanic adults (45% home address-based sample, 55% health facility sample). We examined self-reported counseling on, frequency of use and risks of aspirin for all respondents. For a subgroup free of CAD or cerebral infarction that underwent physical examination, we measured 10-year coronary heart disease risk and blood salicylate concentration.ResultsTwo in five respondents reported using aspirin routinely while one in five with a history of CAD or cerebral infarction and without contraindication did not report routine use of aspirin. Women with these conditions used less aspirin than men (65.0% vs. 76.5%) and reported more health problems that would make aspirin unsafe (29.4% vs. 21.2%). In a subgroup undergoing phlebotomy a third of respondents with low cardiovascular risk used aspirin routinely and only 4.6% of all aspirin users had no detectable salicylate in their blood.ConclusionsIn this large urban county where health care delivery should be of high quality, there is insufficient aspirin use among those with high cardiovascular risk or disease and routine aspirin use by many at low risk. Further efforts are needed to promote shared-decision making between patients and clinicians as well as inform the public about appropriate use of routine aspirin to reduce the burden of atherosclerotic vascular disease.

Randomized trial of a health communication intervention for parents of children with asthma

Abstract Objective: To determine if a health communication intervention targeting parents of high-risk, urban, minority children with asthma could (i) improve parental perceptions of connectedness to and communication with their childs primary care providers (PCP) and (ii) decrease reliance on emergency departments (EDs) and other urgent care services for their childs asthma-related care. Methods: The design was a single blind, parallel groups, randomized controlled trial. Parents were recruited from an ED-based asthma clinic serving primarily low-income, minority children in Washington, DC. The intervention involved face-to-face education on effective communication followed by a single booster call. Standardized instruments were administered to assess primary care connectedness and healthcare utilization at baseline and 2- and 6-months post-enrollment. Results: A total of 150 parents of children 1–12 years old were randomized (77 intervention and 73 usual care), and 137 (91%) were successfully followed for six months. Only at the two-month follow-up time-point, parents in the intervention group were significantly more likely to identify a PCP as the main source of their childs asthma care (adjusted odds ratio: 12.6, 95% confidence interval: 1.1–142.1) and to report a significant reduction in ED visits for asthma care (adjusted incidence rate ratio: 0.3, 95% confidence interval: 0.1–0.8). There was no significant effect on parent communication self-efficacy or number of PCP visits. Conclusions: A brief, in-person health communication intervention for parents of high-risk children with asthma resulted in improved identification of PCPs as the usual source of asthma care and reduced reliance on EDs for asthma care, albeit only for two months post-intervention.

Health-care access and uptake of influenza vaccination among pregnant women in the USA: a cross-sectional survey

Abstract Background Due to the high risk of influenza-related complications, including severe illness and premature death, WHO recommends that pregnant women receive influenza vaccination. However, current seasonal influenza vaccination rates among pregnant women in the USA are still below the Healthy People 2020 target of 80%. We identified the predictors of the uptake of influenza vaccination among pregnant women. Methods Self-reported survey data from the 2011 Behavioral Risk Factor Surveillance System (BRFSS) were analysed. The study sample included 1931 pregnant women aged 18–44 years surveyed during seasonal influenza seasons from January to May and October to December, 2011. We examined three categories of predictors: sociodemographics, health status, and health-care access. We used stratified, weighted, multivariable logistic regression to compute the odds of receiving the influenza vaccine in the past 12 months and to adjust for potential confounders. Findings The influenza vaccination coverage level among pregnant women was 37·1% (95% CI 33·4–40·9). Those not college educated were less likely to report vaccination (adjusted odds ratio [aOR] 0·63, 95% CI 0·40–0·997). Adjusting for sociodemographics and health status, an indicator of health-care access, not seeing a doctor due to cost in the past year was significantly associated with lower odds of vaccine uptake (aOR 0·47, 95% CI 0·29–0·75). Reporting not having a general physical exam in the past year was marginally associated with lower odds of receipt of influenza vaccine (aOR 0·70, 95% CI 0·48–1·02). Age, ethnic origin, marital status, living with children less than 18 years of age, employment status, and physical and mental health status were not significantly associated with influenza vaccination among pregnant women. Interpretation Our results showed that health-care access and utilisation are strong predictors of influenza vaccination among pregnant women. Counselling on the importance of influenza vaccination should be routinely performed as part of prenatal care. Funding None.

Validation of a new predictive risk model: measuring the impact of the major modifiable risks of death for patients and populations.

BackgroundModifiable risks account for a large fraction of disease and death, but clinicians and patients lack tools to identify high risk populations or compare the possible benefit of different interventions.MethodsWe used data on the distribution of exposure to 12 major behavioral and biometric risk factors inthe US population, mortality rates by cause, and estimates of the proportional hazards of risk factor exposure from published systematic reviews to develop a risk prediction model that estimates an adult’s 10 year mortality risk compared to a population with optimum risk factors. We compared predicted risk to observed mortality in 8,241 respondents in NHANES 1988-1994 and NHANES 1999-2004 with linked mortality data up to the end of 2006.ResultsPredicted risk showed good discrimination with an area under the receiver operating characteristic (ROC) curve of 0.84 (standard error 0.01) for women and 0.84 (SE 0.01) for men. Across deciles of predicted risk, mortality was accurately predicted in men ((Χ2 statistic = 12.3 for men, p=0.196) but slightly overpredicted in the highest decile among women (Χ2 statistic = 22.8, p=0.002). Mortality risk was highly concentrated; for example, among those age 30-44 years, 5.1 % (95 % CI 4.1 % - 6.0 %) of the male and 5.9 % (95 % CI 4.8 % - 6.9 %) of the female population accounted for 25 % of the risk of death.ConclusionThe risk model accurately predicted mortality in a representative sample of the US population and could be used to help inform patient and provider decision-making, identify high risk groups, and monitor the impact of efforts to improve population health.