Biomedical subjects

James P Hughes

Publications and source records attributed to James P Hughes.

At least 19 recordsLinked to original sources

PubMed2007

Statistical methods for determining the accuracy of quantitative polymerase chain reaction-based tests.

Quantitative polymerase chain reaction (PCR)-based tests are used in several different scientific fields to determine levels of a target DNA sequence of interest (the target molecule). The accuracy of quantitative PCR-based tests can be assessed by using the assay to determine the number of copies of the target molecule in a sample with a known concentration of the target molecule. For example, a sample with a known concentration of a target DNA sequence is serially diluted into replicate aliquots and these are tested to determine if the observed quantity of the target is close to the expected quantity (given the concentration in the original sample and the dilution). Statistical methods that are conventionally used to assess the accuracy of these assays do not take into account the variability in the number of target molecules in each aliquot from the original sample. We develop methods that take into account this extra variation and which determine the accuracy of quantitative PCR-based tests in estimating the number of target molecules based on a set of assays of serial dilutions from an original sample with a known concentration of target molecules. These methods are applied to data from an experiment to test the accuracy of a real-time PCR assay at low HIV-1 DNA copy levels.

DNA, Viral↗

PubMed2007

Concordance of self-collected and clinician-collected swab samples for detecting human papillomavirus DNA in women 18 to 32 years of age.

OBJECTIVE: The objective of this study was to determine whether self- and clinician-collected samples are comparable for human papillomavirus (HPV) detection. STUDY DESIGN: Three hundred seventy-four women aged 23 to 32 (population 1) and 211 women aged 18 to 25 (population 2) contributed self-collected vaginal and clinician-collected cervical and vulvovaginal samples for HPV DNA testing. Eighty-six women mailed in self-collected samples. RESULTS: Agreement between self-collected vaginal and clinician-collected combined cervical/vulvovaginal samples was excellent (population 1:92.0%, kappa = 0.81; population 2: 96.4%, kappa = 0.88), but self-collected samples were more concordant with clinician-collected cervical samples in population 2 (kappa = 0.84) than population 1 (kappa = 0.65) (P = 0.01). Age-adjusted HPV prevalence was slightly lower in mailed-in (21.5%) than in-clinic self-collected samples (26.8%). CONCLUSIONS: The combined clinician-collected cervical/vulvovaginal sample is most sensitive for detecting all female genital tract HPV infections. HPV concordance between cervical and vaginal samples may be better for newer infections. Larger studies are needed to determine whether mailed-in self-samples are as effective as those collected in a clinical setting.

Adolescent↗

PubMed2006

Male circumcision, religion, and infectious diseases: an ecologic analysis of 118 developing countries.

BACKGROUND: Both religious practices and male circumcision (MC) have been associated with HIV and other sexually-transmitted infectious diseases. Most studies have been limited in size and have not adequately controlled for religion, so these relationships remain unclear. METHODS: We evaluated relationships between MC prevalence, Muslim and Christian religion, and 7 infectious diseases using country-specific data among 118 developing countries. We used multivariate linear regression to describe associations between MC and cervical cancer incidence, and between MC and HIV prevalence among countries with primarily sexual HIV transmission. RESULTS: Fifty-three, 14, and 51 developing countries had a high (>80%), intermediate (20-80%), and low (<20%) MC prevalence, respectively. In univariate analyses, MC was associated with lower HIV prevalence and lower cervical cancer incidence, but not with HSV-2, syphilis, nor, as expected, with Hepatitis C, tuberculosis, or malaria. In multivariate analysis after stratifying the countries by religious groups, each categorical increase of MC prevalence was associated with a 3.65/100,000 women (95% CI 0.54-6.76, p = 0.02) decrease in annual cervical cancer incidence, and a 1.84-fold (95% CI 1.36-2.48, p < 0.001) decrease in the adult HIV prevalence among sub-Saharan African countries. In separate multivariate analyses among non-sub-Saharan African countries controlling for religion, higher MC prevalence was associated with a 8.94-fold (95% CI 4.30-18.60) decrease in the adult HIV prevalence among countries with primarily heterosexual HIV transmission, but not, as expected, among countries with primarily homosexual or injection drug use HIV transmission (p = 0.35). CONCLUSION: Male circumcision was significantly associated with lower cervical cancer incidence and lower HIV prevalence in sub-Saharan Africa, independent of Muslim and Christian religion. As predicted, male circumcision was also strongly associated with lower HIV prevalence among countries with primarily heterosexual HIV transmission, but not among countries with primarily homosexual or injection drug use HIV transmission. These findings strengthen the reported biological link between MC and some sexually transmitted infectious diseases, including HIV and cervical cancer.

Africa South of the Sahara↗

PubMed2006

Design and analysis of stepped wedge cluster randomized trials.

Cluster randomized trials (CRT) are often used to evaluate therapies or interventions in situations where individual randomization is not possible or not desirable for logistic, financial or ethical reasons. While a significant and rapidly growing body of literature exists on CRTs utilizing a "parallel" design (i.e. I clusters randomized to each treatment), only a few examples of CRTs using crossover designs have been described. In this article we discuss the design and analysis of a particular type of crossover CRT - the stepped wedge - and provide an example of its use.

Adolescent↗

PubMed2006

Condom use and the risk of genital human papillomavirus infection in young women.

BACKGROUND: To evaluate whether the use of male condoms reduces the risk of male-to-female transmission of human papillomavirus (HPV) infection, longitudinal studies explicitly designed to evaluate the temporal relationship between condom use and HPV infection are needed. METHODS: We followed 82 female university students who reported their first intercourse with a male partner either during the study period or within two weeks before enrollment. Cervical and vulvovaginal samples for HPV DNA testing and Papanicolaou testing were collected at gynecologic examinations every four months. Every two weeks, women used electronic diaries to record information about their daily sexual behavior. Cox proportional-hazards models were used to evaluate risk factors for HPV infection. RESULTS: The incidence of genital HPV infection was 37.8 per 100 patient-years at risk among women whose partners used condoms for all instances of intercourse during the eight months before testing, as compared with 89.3 per 100 patient-years at risk in women whose partners used condoms less than 5 percent of the time (adjusted hazard ratio, 0.3; 95 percent confidence interval, 0.1 to 0.6, adjusted for the number of new partners and the number of previous partners of the male partner). Similar associations were observed when the analysis was restricted to high-risk and low-risk types of HPV and HPV types 6, 11, 16, and 18. In women reporting 100 percent condom use by their partners, no cervical squamous intraepithelial lesions were detected in 32 patient-years at risk, whereas 14 incident lesions were detected during 97 patient-years at risk among women whose partners did not use condoms or used them less consistently. CONCLUSIONS: Among newly sexually active women, consistent condom use by their partners appears to reduce the risk of cervical and vulvovaginal HPV infection.

Adolescent↗

PubMed2005

Comparison of oral fluid and serum ELISAs in the determination of IgG response to natural human papillomavirus infection in university women.

BACKGROUND: Venipuncture (phlebotomy) is an obstacle to subject recruitment and ongoing participation in cohort studies investigating human papillomavirus (HPV) infection. Anti-HPV antibodies are not only detected in serum but also in oral fluid. OBJECTIVES: To evaluate if oral fluid specimens can be used in lieu of blood specimens for determining HPV antibody status. STUDY DESIGN: One hundred and seven paired oral fluid and blood specimens from female university students were tested in a HPV16 ELISA and compared to sexual history and serial genital HPV16 DNA status. RESULTS: ELISA results were in agreement in 97% (104/107) of paired sera and oral fluid. Of six women with positive anti-HPV16 serum samples, only three had positive oral fluid specimens. However, the specificity of the oral fluid test was 100% compared to the blood test. CONCLUSIONS: Detection of antibodies in oral fluid correlated with antibodies but was less sensitive than sera. A larger validation study is required to fully characterize the oral fluid assay.

Antibodies, Viral↗

PubMed2005

Using baseline data to design a group randomized trial.

Group randomized trials (GRT) are often designed with relatively little preliminary data available to estimate key parameters. In this paper, however, the opposite situation is considered-very good baseline data are available on the primary outcome of interest. These data can then be used to inform key design and analysis decisions such as (i) should the trial be designed as an unmatched or pair-matched study, or stratified in some other fashion; (ii) is analysis of "change from baseline" preferable to using end-of-study data alone; and (iii) what power might be expected by pursuing these various strategies. The results are applied to a GRT for sexually transmitted diseases prevention in Peru.

Data Interpretation, Statistical↗

PubMed2005

Methods for assessing the accuracy of PCR-based tests: comparisons and extensions.

Polymerase chain reaction (PCR) based tests are commonly used to diagnose various infections. Such tests are assumed to be highly 'sensitive', however, no consensus definition of, or method for estimating, sensitivity exists. Hughes and Totten proposed that sensitivity be defined as a function of the number of target DNA molecules in the sample with specificity corresponding to the case where there is no target DNA molecule present. They then developed parametric, non-parametric and semi-parametric models for estimating the sensitivity curve. In this paper a general model is proposed that yields their three models as special cases when specificity is assumed to be 1.0. We also extend the general model to incorporate covariates. Simulation studies are used to compare the different estimators. The methods are applied to data from a PCR-based test for Mycoplasma genitalium.

Algorithms↗

PubMed2005

Effect of expedited treatment of sex partners on recurrent or persistent gonorrhea or chlamydial infection.

BACKGROUND: Many sex partners of persons with gonorrhea or chlamydial infections are not treated, which leads to frequent reinfections and further transmission. METHODS: We randomly assigned women and heterosexual men with gonorrhea or chlamydial infection to have their partners receive expedited treatment or standard referral. Patients in the expedited-treatment group were offered medication to give to their sex partners, or if they preferred, study staff members contacted partners and provided them with medication without a clinical examination. Patients assigned to standard partner referral were advised to refer their partners for treatment and were offered assistance notifying partners. The primary outcome was persistent or recurrent gonorrhea or chlamydial infection in patients 3 to 19 weeks after treatment. RESULTS: Persistent or recurrent gonorrhea or chlamydial infection occurred in 121 of 931 patients (13 percent) assigned to standard partner referral and 92 of 929 (10 percent) assigned to expedited treatment of sexual partners (relative risk, 0.76; 95 percent confidence interval, 0.59 to 0.98). Expedited treatment was more effective than standard referral of partners in reducing persistent or recurrent infection among patients with gonorrhea (3 percent vs. 11 percent, P=0.01) than in those with chlamydial infection (11 percent vs. 13 percent, P=0.17) (P=0.05 for the comparison of treatment effects) and remained independently associated with a reduced risk of persistent or recurrent infection after adjustment for other predictors of infection at follow-up (relative risk, 0.75; 95 percent confidence interval, 0.57 to 0.97). Patients assigned to expedited treatment of sexual partners were significantly more likely than those assigned to standard referral of partners to report that all of their partners were treated and significantly less likely to report having sex with an untreated partner. CONCLUSIONS: Expedited treatment of sex partners reduces the rates of persistent or recurrent gonorrhea or chlamydial infection.

Adult↗

PubMed2005

Development and duration of human papillomavirus lesions, after initial infection.

BACKGROUND: To determine the potential value of human papillomavirus (HPV) vaccines, information concerning the incidence and duration of clinically important lesions is needed. METHODS: A total of 603 female university students were followed for a mean duration of 38.8 months. Triannual gynecologic examinations included cervical and vulvovaginal specimen collection for Pap and HPV DNA testing. Women with cytologic evidence of a high-grade squamous intraepithelial lesion (SIL) were referred for colposcopically directed biopsy. RESULTS: Among women with incident HPV infection, the 36-month cumulative incidence of cervical SILs found by cytologic testing (47.2%; 95% confidence interval [CI], 38.9%-56.4%) was higher than that of vaginal SILs (28.8%; 95% CI, 21.3%-38.2%). The median time to clearance of cervical and vaginal SILs was 5.5 and 4.7 months, respectively. Among women with incident HPV-16 or HPV-18 infection, the 36-month cumulative incidence of cervical intraepithelial neoplasia (CIN) grade 2 was 20.0% (95% CI, 10.8%-35.1%), and that of CIN grade 3 was 6.7% (95% CI, 2.5%-17.0%). The 36-month cumulative incidence of clinically ascertained genital warts among women with incident HPV-6 or HPV-11 infection was 64.2% (95% CI, 50.7%-77.4%). CONCLUSIONS: Intraepithelial lesions are common early events among women with incident HPV infection, and the interval between incident HPV-16 or HPV-18 infection and biopsy-confirmed CIN grade 2-3 appears to be relatively short.

Adolescent↗

PubMed2004

Positive predictive value of Gen-Probe APTIMA Combo 2 testing for Neisseria gonorrhoeae in a population of women with low prevalence of N. gonorrhoeae infection.

We collected specimens from women who tested positive for Neisseria gonorrhoeae using the Gen-Probe APTIMA Combo 2 (AC2), and we performed confirmatory tests using a nucleic acid amplification test (NAAT) that targets alternate gonococcal nucleic acid sequences. Among 59,664 specimens, 280 (0.47%) had positive results using AC2; 265 of these specimens were tested using the confirmatory NAAT, of which 258 yielded positive results (positive predictive value, 97.4%; 95% confidence interval, 95.1%-98.8%). Routine confirmatory testing of specimens with positive AC2 gonorrhea test results is not indicated.

Diagnostic Tests, Routine↗

PubMed2004

Influence of study population on the identification of risk factors for sexually transmitted diseases using a case-control design: the example of gonorrhea.

The population prevalence of many sexually transmitted diseases (STDs) is low. Thus, most epidemiologic studies of STDs are conducted among STD clinic populations to maximize efficiency. However, STD clinic patients have unique sociobehavioral characteristics. To examine the potential effect of study population on identification of risk factors, the authors compared 1) STD clinic patients with a random digit dialing telephone sample, 2) general population cases with random digit dialing controls, and 3) STD clinic cases with STD clinic controls (Seattle, Washington, 1992-1995). Risk factors for gonorrhea identified among STD clinic patients formed a subset of those identified in the general population. In both populations, risk decreased with age (odds ratio for the general population (OR(GP)) = 0.4, 95% confidence interval (CI): 0.22, 0.59; odds ratio for the clinic population (OR(clinic)) = 0.5, 95% CI: 0.30, 0.81) and was increased among Blacks (OR(GP) = 15.5, 95% CI: 4.93, 49.0; OR(clinic) = 10.5, 95% CI: 4.51, 24.68) and persons whose partner had been jailed (OR(GP) = 5.4, 95% CI: 2.07, 13.9; OR(clinic )= 3.1, 95% CI: 1.32, 7.30). Additional factors associated with gonorrhea in the general population included secondary education (OR = 0.3, 95% CI: 0.11, 0.70), anal intercourse (OR = 10.5, 95% CI: 2.01, 54.7, STD history (OR = 5.9, 95% CI: 1.76, 19.5), meeting partners in structured settings (OR = 0.2, 95% CI: 0.09, 0.50), no condom use (OR = 3.2, 95% CI: 1.30, 7.89), and divorce (OR = 3.6, 95% CI: 1.07, 11.9). Risk factors identified in STD clinics will probably be confirmed in a general population sample, despite overcontrolling for shared behaviors; however, factors associated with both disease and STD clinic attendance may be missed.

Adolescent↗

PubMed2004

Higher concentration of HIV RNA in rectal mucosa secretions than in blood and seminal plasma, among men who have sex with men, independent of antiretroviral therapy.

High levels of human immunodeficiency virus (HIV) in rectal secretions and semen likely increase the risk of HIV transmission. HIV-infected men who have sex with men made 2-3 study visits, over 4 weeks, to assess rectal, seminal, and plasma levels of HIV RNA. Mixed-effects models estimated the effect of factors on HIV shedding. Twenty-seven (42%) of 64 men were receiving antiretroviral therapy (ART); regardless of ART use, median HIV RNA levels were higher in rectal secretions (4.96 log(10) copies/mL) than in blood plasma (4.24 log(10) copies/mL) or seminal plasma (3.55 log(10) copies/mL; P<.05, each comparison). ART was associated with a 1.3-log(10) reduction in rectal HIV RNA in a model without plasma HIV RNA; with and without plasma RNA in models, ART accounted for a >1-log(10) decrease in seminal HIV RNA levels. Thus, controlling for plasma HIV RNA, ART had an independent effect on seminal, but not rectal, HIV levels.

Adult↗

PubMed2004

Correlates of national HIV seroprevalence: an ecologic analysis of 122 developing countries.

BACKGROUND: Ecologic analyses of social and developmental correlates of country-level HIV seroprevalence may suggest strategies for combating the HIV/AIDS epidemic. METHODS: Regression analyses were performed for 81 variables obtained primarily from United Nation agencies for 122 developing countries. Variable measures were compared between highest and lowest tertiles of HIV seroprevalence. RESULTS: Geography, religion, and income inequality were independently associated with HIV seroprevalence. Countries with earlier ages at first sex, higher teenage birth rates, and higher fertility rates had higher HIV seroprevalence. Countries with high HIV seroprevalence had fewer women using contraceptives, more persons with casual sex partners, and higher herpes simplex virus 2 seroprevalence. Male circumcision and Muslim religion were colinearly associated with lower HIV seroprevalence. Countries with high HIV seroprevalence had fewer doctors, more midwives, and less access to essential medications, but health spending differences were minor. CONCLUSIONS: Ecologic analyses support population-level behavioral approaches, such as delaying sexual debut and discouraging casual sex partners, and reinforce biologic measures, such as controlling sexually transmitted infections and promoting male circumcision, for HIV prevention. Fewer births attended by skilled personnel, but more midwives, in countries with the highest HIV seroprevalence suggest potential strategies for reducing mother-to-child transmission. Correlations with selected health indicators suggest additional obstacles for implementing HIV treatment programs.

Adolescent↗

PubMed2004

Randomised treatment trial of bacterial vaginosis to prevent post-abortion complication.

OBJECTIVE: To evaluate the efficacy of metronidazole to reduce post-abortion complications among women with bacterial vaginosis. DESIGN: A randomised, double-blind placebo-controlled trial. SETTING: An American outpatient abortion facility between April 1999 and June 2000. SAMPLE: Women presenting for surgical abortion were screened for bacterial vaginosis using a pH and amines card test. METHODS: Women positive for elevated pH and amines on a self-collected vaginal discharge sample were randomised to 1000 mg oral metronidazole before abortion followed by 500 mg twice daily or placebo. All randomised women were also dispensed 100 mg doxycycline to take twice daily for seven days. MAIN OUTCOME MEASURES: Data were collected by phone, daily diary or visit and scored from 0 to 7 for post-abortion complications. Intention-to-treat analyses were completed prior to unblinding. RESULTS: Of 1764 women screened by card test, 638 (36%) were positive. Of these, 393 were randomised. Follow up data were available for 253 (64%) of these women. A complication score of 3 or more occurred in 21% of women assigned to metronidazole, compared with 19% in those assigned placebo (RR 1.1, 95% CI 0.7-1.9). Among 153 women with Gram stain confirmation for bacterial vaginosis, there was a similar lack of benefit with treatment (RR 1.6, 95% CI 0.9-3.0). No individual symptom or sign was statistically different between groups even for second trimester procedures. CONCLUSION: Among women undergoing abortion and diagnosed with bacterial vaginosis, oral metronidazole, in conjunction with doxycycline, did not reduce post-abortion complications.

Abortion, Induced↗

PubMed2003

Characterization of IgA response among women with incident HPV 16 infection.

Previous studies have characterized the prevalence and duration of serum IgG antibodies to human papillomavirus type 16 (HPV 16) in a well-studied cohort of college women, using viruslike particle- (VLP) based ELISAs. In this study IgA antibodies in cervical secretions and sera were examined using a newly developed capsomer-based ELISA and the patterns observed for serum IgG, serum IgA, and cervical IgA antibodies were compared. The median time to antibody detection from the first detection of HPV 16 DNA was 10.5 months for IgA in cervical secretions and 19.1 months for serum IgA. Serum IgA antibody conversion was observed less frequently and occurred later than IgA conversion in cervical secretions (P = 0.011) or serum IgG conversion (P = 0.051). The median time to antibody reversion, following seroconversion, was 12.0 months for IgA in cervical secretions and 13.6 months for serum IgA, whereas approximately 20% of women with serum IgG antibodies reverted within 36 months. Thus, the duration of IgA in cervical secretions and sera was shorter than the duration of serum IgG (P = 0.007 and 0.001).

Adult↗

PubMed2003

Factors associated with oropharyngeal human immunodeficiency virus shedding.

Orogenital transmission of human immunodeficiency virus (HIV) is considered to be inefficient, and infectious HIV is rarely detected in saliva. To evaluate the posterior oropharynx as a source of HIV shedding, we studied 64 HIV-infected men who have sex with men in Seattle, Washington, and Lima, Peru. In multivariate analysis, receipt of antiretroviral therapy, higher CD4 cell count, and history of tonsillectomy were predictors of lower pharyngeal HIV RNA levels.

Adult↗

PubMed2003

Applications of continuous time hidden Markov models to the study of misclassified disease outcomes.

Disease progression in prospective clinical and epidemiological studies is often conceptualized in terms of transitions between disease states. Analysis of data from such studies can be complicated by a number of factors, including the presence of individuals in various prevalent disease states and with unknown prior disease history, interval censored observations of state transitions and misclassified measurements of disease states. We present an approach where the disease states are modelled as the hidden states of a continuous time hidden Markov model using the imperfect measurements of the disease state as observations. Covariate effects on transitions between disease states are incorporated using a generalized regression framework. Parameter estimation and inference are based on maximum likelihood methods and rely on an EM algorithm. In addition, techniques for model assessment are proposed. Applications to two binary disease outcomes are presented: the oral lesion hairy leukoplakia in a cohort of HIV infected men and cervical human papillomavirus (HPV) infection in a cohort of young women. Estimated transition rates and misclassification probabilities for the hairy leukoplakia data agree well with clinical observations on the persistence and diagnosis of this lesion, lending credibility to the interpretation of hidden states as representing the actual disease states. By contrast, interpretation of the results for the HPV data are more problematic, illustrating that successful application of the hidden Markov model may be highly dependent on the degree to which the assumptions of the model are satisfied.

Adolescent↗