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ABSTRACT: OBJECTIVE: To evaluate the safety of semen washing with intrauterine insemination (SW-IUI) for achieving pregnancy when the man is HIV-infected and the woman is HIV-negative. STUDY DESIGN: We conducted a retrospective analysis of 635 HIV-discordant couples enrolled in a SW-IUI program, and followed back 367 Italian women. We computed pregnancy, live birth, and multiple delivery rates, and assessed the women's post-insemination HIV status. RESULTS: The retrospective analysis included 635 couples (2,113 SW-IUI cycles): 41% of the women (95% confidence interval (CI): 37%-45%) had a live birth (per-cycle live birth rate: 13%, CI: 11%-14%). HIV status after SW-IUI was negative when available but unknown for 26% of the women: missing HIV status was not associated with correlates of HIV risk. The follow-back study included 367 couples (1,365 cycles): 47% of the women (CI: 42%-52%) had a live birth (per-cycle rate: 14%, CI: 12%-16%). Ascertainment of post-insemination HIV status was complete and confirmed no HIV transmission attributable to SW-IUI. The upper 95% confidence limit of the HIV transmission rate was 1.8 per 1,000 cycles in the retrospective analysis and 2.7 per 1,000 cycles in the follow-back study. CONCLUSIONS: SW-IUI appears to be a safe and effective method for achieving pregnancy in HIV-discordant couples where the man is HIV-infected.
American journal of obstetrics and gynecology 02/2013; · 3.28 Impact Factor
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Clive Anderson,
Maria F Gallo,
Tina Hylton-Kong,
Markus J Steiner,
Marcia M Hobbs, Maurizio Macaluso,
J Peter Figueroa,
Denise J Jamieson,
Jennifer Legardy-Williams,
Jeffrey Wiener,
Lee Warner
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ABSTRACT: BACKGROUND: The effectiveness of counseling messages to avoid unprotected sex during short-term treatment for curable sexually transmitted infections is unknown. METHODS: We randomized 300 female STI clinic patients 18 years or older with cervicitis and/or vaginal discharge in Kingston, Jamaica, in 2010 to 2011, to 1 of 2 counseling messages for their course of syndromic treatment: abstinence only or abstinence backed up by condom use. At a follow-up visit 6 days afterward, we collected vaginal swabs to test for prostate-specific antigen (PSA), a biological marker of recent semen exposure, and administered a questionnaire assessing sexual behavior. RESULTS: No differences were found in the proportions of women testing positive for PSA at follow-up in the abstinence-plus-condom group (11.9%) and abstinence-only group (8.4%) (risk difference, 3.5; 95% confidence interval, -3.5 to10.5). There also was no significant difference in reporting of unprotected sex between groups. Reporting a history of condom use before enrollment significantly modified the effect of counseling arm on PSA positivity (P = 0.03). Among those reporting recent condom use, 10.3% in the abstinence-only arm and 4.8% in the abstinence-plus-condom arm tested positive for PSA. Conversely, among those not reporting recent condom use, 6.5% in the abstinence-only arm and 17.3% in the abstinence-plus-condom arm had PSA detected. CONCLUSIONS: We found no evidence to support the superiority of either counseling message. Post hoc analyses suggest that women with recent condom experience may benefit significantly more from abstinence-plus-condom messages, whereas women without such experience may benefit significantly more from abstinence-only messages. Providers should weigh individual condom use history when determining the most appropriate counseling message.
Sexually transmitted diseases 02/2013; 40(2):105-110. · 2.58 Impact Factor
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ABSTRACT: BACKGROUND: Prostate-specific antigen (PSA) is a biomarker of recent semen exposure. There is currently only limited information on whether topical vaginal products affect PSA assays. We investigated this question using various dilutions of several vaginal products (lubricants and spermicides) and the Abacus ABAcard for PSA detection. STUDY DESIGN: Pooled semen controls and various dilutions of nonoxynol-9 (N9), carboxymethyl cellulose (CMC), Replens, Gynol 2, K-Y jelly, Astroglide, Surgilube, combined with pooled semen dilutions, were tested for PSA using the Abacus ABAcard. RESULTS: N9 (2% with saline) and CMC did not appear to affect the results of testing with the ABAcard, but not all semen dilutions were tested. The other products (including Replens and Gynol, which is 2% N9 with propylene glycol, K-Y, Astroglide and Surgilube) at some of the dilutions tested either affected or gave invalid results with PSA testing using the ABAcard. Both Gynol 2 and K-Y at 1:10 dilution gave false-positive results. CONCLUSIONS: Some vaginal products affect PSA results obtained by using the semiquantitative ABAcard. In vivo confirmation is necessary to further optimize PSA detection when topical vaginal products are present.
Contraception 12/2012; · 2.72 Impact Factor
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ABSTRACT: BACKGROUND: Prostate-specific antigen (PSA) detected in vaginal fluid can be used in studies of HIV/sexually transmitted infection (STI) and pregnancy prevention as an alternative to relying on participant reports of exposure to semen. Optimal methods for collecting and storing specimens for this testing have not been determined. STUDY DESIGN: We conducted a controlled, in vitro experiment of 550 specimens spiked with semen to determine the effects of swab type (five types), storage conditions of the swabs (room temperature with or without desiccant or at -80°C without desiccant) and time from collection to testing (seven intervals over the course of 12 months) on the identification of PSA. We performed factorial analysis of variance to identify factors influencing PSA detection. RESULTS: Concentrations of PSA detected in the swabs declined with time of storage over the 1-year experiment (p<.01). The 1-mL, rayon-tipped swab stored immediately at -80°C following collection performed best. CONCLUSIONS: If immediate testing or freezer storage is not feasible, investigators should use a swab with 1-mL capacity with processing and testing as soon as possible after specimen collection.
Contraception 10/2012; · 2.72 Impact Factor
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ABSTRACT: Florida resident birth certificates for 2004-2006 were linked to the Centers for Disease Control and Prevention's National ART Surveillance System and were used to investigate 1) whether the association of assisted reproductive technology (ART) with preterm birth varies by prepregnancy body mass index and 2) whether the association varies by plurality. Preterm birth was defined as early preterm birth (gestation <34 weeks) and late preterm birth (gestation 34-36 weeks). Descriptive statistics and multinomial logistic regression were used to explore maternal and infant differences by ART status and plurality. Of 581,403 women included in the study, 24.0% were overweight, 18.6% were obese, 7.3% had late preterm birth, 2.6% had early preterm birth, and 0.67% conceived through ART. Among singleton births, ART was associated with increased early preterm birth risk among underweight (odds ratio (OR) = 2.94, 95% confidence interval (CI): 1.27, 6.81), overweight (OR = 1.75, 95% CI: 1.12, 2.72), and obese (OR = 2.37, 95% CI: 1.51, 3.71) women. Among twins, ART was significantly associated with increased risk among overweight (OR = 1.61, 95% CI: 1.12, 2.32) and obese (OR = 1.85, 95% CI: 1.18, 2.90) women. Differences in the associations between ART and early preterm birth by body mass index and plurality warrant further investigation.
American journal of epidemiology 10/2012; · 5.59 Impact Factor
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ABSTRACT: : To estimate trends in good perinatal outcomes (singleton live births at term with birthweight more than 2,500 g) among live births after assisted reproductive technology in the United States from 2000 to 2008, and associated factors among singletons in 2008.
: Using retrospective cohort data from the National Assisted Reproductive Technology Surveillance System from 2000 to 2008, we calculated relative change and χ tests for trend in the proportion of good perinatal outcomes among assisted reproductive technology live births (n=444,909) and liveborn singletons (n=222,500). We conducted univariable analyses followed by multiple logistic regression to estimate the effects of various characteristics on the outcome among singletons born in 2008 after fresh, nondonor assisted reproductive technology cycles (n=20,780).
: The proportion of good perinatal outcomes among all liveborn neonates increased from 38.6% in 2000 to 42.5% in 2008, whereas it declined marginally among singletons from 83.6% to 83.4%. One previous birth, transfer of fewer than three embryos, and the presence of fewer than three fetal hearts on 6-week ultrasound examination were associated with good perinatal outcome among singletons. Non-Hispanic black race, tubal factor infertility, uterine factor infertility, ovulatory disorder, and 5-day embryo culture were associated with reduced odds for a good outcome. The strongest association was the presence of one fetal heart compared with more than two (adjusted odds ratio 2.43, 95% confidence interval 1.73-3.42).
: From 2000 to 2008, good perinatal outcomes increased among assisted reproductive technology live births. Among singleton live births, odds for good outcome were greatest with the presence of a single fetal heart and lowest in women of non-Hispanic black race.
: II.
Obstetrics and Gynecology 10/2012; 120(4):843-51. · 4.73 Impact Factor
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ABSTRACT: We explored the use of qualitative interviews to discuss discrepancies between two sources of information on unprotected sex: biomarker results and self-reported survey data. The study context was a randomized trial in Kingston, Jamaica examining the effect of STI counseling messages on recent sexual behavior using prostate-specific antigen (PSA) as the primary study outcome. Twenty women were interviewed. Eleven participants were selected because they tested positive for PSA indicating recent semen exposure, yet reported no unprotected sex in a quantitative survey ("discordant"): 5 reported abstinence and 6 reported condom use. Nine participants who also tested positive for PSA but reported unprotected sex in the survey were interviewed for comparison ("concordant"). Qualitative interviews with 6 of the 11 discordant participants provided possible explanations for their PSA test results, and 5 of those were prompted by direct discussion of those results. Rapid PSA testing combined with qualitative interviews provides a novel tool for investigating and complementing self-reported sexual behavior.
AIDS and Behavior 08/2012; · 3.49 Impact Factor
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ABSTRACT: STUDY QUESTION: What characteristics are associated with a Day 5 embryo transfer? SUMMARY ANSWER: The use of the Day 5 embryo transfer has increased over time, with clinicians allowing women with typically 'poorer' prognostic characteristics to undergo a Day 5 embryo transfer. The mean number of embryos per Day 5 transfer decreased from 2001 to 2009, although the prevalence of the Day 5 single embryo transfer remains low and the rate of multiple births remains substantial. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Day 5 embryo transfer may reduce the rate of multiple gestation pregnancy. US trends over time in the prevalence of the Day 5 transfer, changes in characteristics of patients receiving Day 5 transfer, and number of embryos transferred are unknown. DESIGN: We used 2001-2009 US National assisted reproductive technology (ART) Surveillance System (NASS) data on 620,295 fresh IVF cycles derived from autologous oocytes with a Day 3 or 5 embryo transfer. Trends in the mean number of embryos transferred from 2001 to 2009 were assessed by the day of transfer. For 349,947 cycles from clinics performing both Days 3 and 5 embryo transfers, multivariable logistic regression was used to determine the characteristics associated with the Day 5 embryo transfer. We also compared the characteristics of the Day 5 embryo cycles in 2001 and 2009. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, the proportion of ART cycles using the Day 5 embryo transfer increased from 12% in 2001 to 36% in 2009 (P<0.0001), while the mean number of embryos transferred decreased from 2.4 to 2.1 (P<0.0001). Among Day 5 transfers, the rate of the single embryo transfer tripled from 4.5% in 2001 to 14.8% in 2009 (P<0.0001); and the rate of multiple births decreased from 44.8 to 41.1% (P<0.0001). In cycles initiated after 2001, maternal age<35 years, no prior ART cycles, ≥1 prior pregnancies, baseline follicle stimulating hormone<10 international units and ≥10 oocytes retrieved were associated with the Day 5 embryo transfer. Compared with 2001, in 2009, a broader range of candidates received the Day 5 transfer. BIAS Women undergoing multiple ART cycles over time are not linked. CONFOUNDING FACTORS AND OTHER REASONS FOR CAUTION: We ran multivariable logistic regression to lessen the effects of the confounding factors. Cycle cancelation rates by the day of embryo transfer are unknown. GENERALIZABILITY TO OTHER POPULATIONS: Generalizable to ART clinics included in NASS. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Centres for Disease Control. The authors have no competing interests to declare.
Human Reproduction 05/2012; 27(8):2325-31. · 4.47 Impact Factor
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ABSTRACT: Studies that evaluate condom effectiveness are affected by factors related to how the condom was used, and these factors may not be consistent between different types of condoms. Also, subjective assessments of the sexual act may be unreliable.
We performed a secondary data analysis of a randomized crossover trial of male and female condoms among 108 couples.
Self-reported duration and activeness of coital acts were significantly different for uses of the male condom compared to uses of the female condom. Fewer individuals reported ejaculation occurring with the female condom. Reliability of self-reports of ejaculation compared to a biological marker of semen detected inside the used male and female condoms was not strong.
We found that sexual behaviors appear to differ by the type of condom used for the coital act. Studies should consider sexual behavior when evaluating condom effectiveness. Furthermore, studies would be strengthened by the use of a biological marker of semen to determine whether ejaculation, and therefore a true risk of exposure, occurred.
Contraception 03/2012; 86(4):391-6. · 2.72 Impact Factor
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ABSTRACT: Interactions between bacterial vaginosis (BV) and inflammatory sexually transmitted infections, such as gonorrhea and chlamydial infection, are not well understood. Furthermore, evidence regarding the sexual transmission of BV is equivocal.
We assessed associations between incident BV and incidences of gonorrhea and/or chlamydial infection ("gonorrhea/chlamydia"), as well as similarities in associations for the two processes, among 645 female patients at a sexually transmitted disease clinic in Alabama followed prospectively for 6 months from 1995 to 1998. We identified predictors of both incident BV and gonorrhea/chlamydia and used bivariate logistic regression to determine whether these predictors differed.
Participants completed 3188 monthly, follow-up visits. Several factors associated with incident BV involved sexual intercourse: young age (<16 years) at first intercourse (adjusted odds ratio [aOR], 1.5; 95% confidence interval [CI], 1.1-1.9), recent drug use during sex (aOR, 1.7; 95% CI, 1.2-2.5), prevalent trichomoniasis (aOR, 2.8; 95% CI, 1.7-4.6) and incident syphilis (aOR, 9.7; 95% CI, 1.9-48.4). Few statistical differences between potential factors for BV and gonorrhea/chlamydia emerged. BV appeared to precede the acquisition of gonorrhea/chlamydia (pairwise odds ratio, 1.6; 95% CI, 1.1-2.3), and vice versa (pairwise odds ratio, 2.4; 95% CI, 1.7-3.5).
Findings are consistent with a causal role of sexual behavior in the acquisition of BV and confirm that BV facilitates acquisition of gonorrhea/chlamydia and vice versa independently from other risk factors.
Annals of epidemiology 12/2011; 22(3):213-20. · 2.95 Impact Factor
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ABSTRACT: Vasectomy has been found to be a highly cost-effective contraceptive method. For couples, tubal sterilization and vasectomy have the same result, but the two methods are used by different segments of the population.
We conducted an analysis of data from male and female samples of the 2006-2008 National Survey of Family Growth, nationally representative samples of men and women in the United States aged 15-44 years.
Among married men, 13.1% reported vasectomies (95% confidence interval 10.4%-16.3%), compared to 21.1% (17.8%-24.9%) of married women who reported tubal sterilizations. Men with higher education and income had greater prevalence of vasectomy than those less educated, while women with lower education and income had the highest prevalence of tubal sterilization.
Efforts to promote vasectomy use need to understand the reasons behind these differences. Increasing the availability and use of vasectomy will require education about its benefits.
Contraception 11/2011; 85(6):552-7. · 2.72 Impact Factor
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ABSTRACT: The prevalence of condom use at last intercourse, estimated from questions added to a national survey, was estimated to be 20.2%. Use of condom was significantly higher for sex outside ongoing relationships and among those with 2 or more past-year sex partners and its use increased slightly but significantly from 1996 to 2008.
Sexually transmitted diseases 10/2011; 38(10):919-21. · 2.58 Impact Factor
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ABSTRACT: To evaluate the determinants of intrauterine device (IUD) use and reasons for choosing IUDs over other reversible contraceptive methods.
Descriptive statistics and multinomial logistic regression were used to assess multiple factors associated with IUD use and the use of other reversible methods in the United States.
Not applicable.
Women at risk of pregnancy from the 2006 to 2008 National Survey of Family Growth and a 2004 Guttmacher Institute survey.
None.
Sociodemographic and reproductive characteristics, family background, and health insurance coverage.
IUD use was positively associated with women's parity and the highest education level of respondent's mother; it was less common among women who had ≥4 sexual partners in the last 12 months and those who were widowed, divorced, or separated. IUD users reported pregnancy prevention, provider recommendation, and no interruption of sex as the most important reasons for choosing the method and reported a high level of satisfaction.
IUD users differed substantially from users of other reversible contraceptives. IUD use was especially uncommon among nulliparae. Most current IUD users were satisfied with their choice.
Fertility and sterility 09/2011; 96(5):1138-44. · 3.97 Impact Factor
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ABSTRACT: To assess the validity of probabilistic linkage (PL) in combining national surveillance data on assisted reproductive technology (ART) with Massachusetts birth and infant death data, for the purpose of monitoring maternal and child health outcomes of ART. A study conducted in 2006 utilized direct identifiers to match Massachusetts birth records with records on ART procedures performed to Massachusetts residents in fertility clinics located in Massachusetts and Rhode Island, achieving a linkage rate of 87.5%. The present study employed PL using the program Link Plus, without access to direct identifiers. The primary linking variables were maternal and infant dates of birth, and plurality. Ancillary variables such as maternal ZIP code and gravidity helped resolve duplicate matches and capture additional matches. PL linked 5,390 (87.8%) of 6,139 deliveries, correctly identifying 96.4% of the matches previously obtained using deterministic linkage methods. PL yielded a high linkage rate with satisfactory validity; this method may be applied in other states to help monitor the maternal and child health outcomes of ART.
Maternal and Child Health Journal 09/2011; · 2.24 Impact Factor
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ABSTRACT: Use of the intrauterine device (IUD) in the United States has recently increased. New evidence for women with employer-sponsored health insurance permits analysis of variation and trends in such use.
A retrospective analysis of annual IUD insertion rates between 2002 and 2008 was conducted by evaluating claims from the MarketScan® Commercial Research Databases for US women insured by plans that covered IUD insertions. Estimates were weighted to be nationally representative.
IUD insertion rates increased from 1.6/1000 women of reproductive age to 9.8/1000 over 2002-2008 and varied substantially by state. Insertion rates of the levonorgestrel-releasing intrauterine system (LNG-IUS) increased from 0.4/1000 to 7.7/1000, whereas the insertion rates of copper T380A IUD (copper IUD) increased from 0.6/1000 to 1.5/1000. IUD insertions, which are most common among women aged 25-34 years, increased at roughly the same rate across all age groups.
The sixfold increase in IUD insertion rates between 2002 and 2008 was accompanied by an increase in the share IUD use with the LNG-IUS from 40% to 85%. Substantial geographic and age variations existed.
Contraception 07/2011; 85(2):155-9. · 2.72 Impact Factor
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ABSTRACT: The objective of the study was to evaluate LINE-1 methylation as an intermediate biomarker for the effect of folate and vitamin B12 on the occurrence of higher grades of cervical intraepithelial neoplasia (CIN ≥ 2).
This study included 376 women who tested positive for high-risk human papillomaviruses and were diagnosed with CIN ≥ 2 (cases) or CIN ≤ 1 (non-cases). CIN ≥ 2 (yes/no) was the dependent variable in logistic regression models that specified the degree of LINE-1 methylation of peripheral blood mononuclear cells (PBMCs) and of exfoliated cervical cells (CCs) as the independent predictors of primary interest. In analyses restricted to non-cases, PBMC LINE-1 methylation (≥ 70% versus <70%) and CC LINE-1 methylation (≥ 54% versus <54%) were the dependent variables in logistic regression models that specified the circulating concentrations of folate and vitamin B12 as the primary independent predictors.
Women in the highest tertile of PBMC LINE-1 methylation had 56% lower odds of being diagnosed with CIN ≥ 2 (odds ratio 0.44, 95% confidence interval 0.24-0.83, P = 0.011), whereas there was no significant association between degree of CC LINE-1 methylation and CIN ≥ 2 (odds ratio 0.86, 95% confidence interval 0.51-1.46, P = 0.578). Among non-cases, women with supraphysiologic concentrations of folate (>19.8 ng/mL) and sufficient concentrations of plasma vitamin B12 (≥ 200.6 ng/mL) were significantly more likely to have highly methylated PBMCs compared with women with lower folate and lower vitamin B12 (odds ratio 3.92, 95% confidence interval 1.06-14.52, P = 0.041). None of the variables including folate and vitamin B12 were significantly associated with CC LINE-1 methylation.
These results suggest that a higher degree of LINE-1 methylation in PBMCs, a one-carbon nutrient-related epigenetic alteration, is associated with a lower risk of developing CIN.
Nutrition 05/2011; 27(5):513-9. · 3.03 Impact Factor
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ABSTRACT: The objectives of this study were to determine risk factors for early (less than 34 weeks gestation) and late (34-36 weeks gestation) preterm singleton birth, by assisted reproductive technology (ART) status. We linked data from Massachusetts birth records and ART records representing singleton live births from 1997 through 2004. Using multinomial regression models, we assessed risk factors for early and late preterm birth by ART status. From 1997 to 2004 in Massachusetts, among non-ART births, risk factors for early and late preterm birth were similar and included women <15 and ≥ 35 years of age, those of non-white race or Hispanic ethnicity, those with ≤ 12 years of education, those with chronic diabetes, those with gestational diabetes, those with gestational hypertension, those who smoked during pregnancy, those who used fertility medications, and those who had not had a previous live birth. Among ART births, risk factors for early and late preterm birth differed and odds of early preterm birth were increased among women with ≤ 12 years of education while odds of late preterm birth were increased among women with gestational diabetes. Odds of both early and late preterm birth were increased among women of non-white race or Hispanic ethnicity and among women with gestational hypertension. Among non-ART births, increased risk for preterm birth was more strongly related to socioeconomic factors than among ART births. Medical conditions were associated with an increased risk for preterm birth regardless of women's ART status. Efforts to prevent preterm births should focus on reducing modifiable risk factors.
Maternal and Child Health Journal 04/2011; 16(4):807-13. · 2.24 Impact Factor
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ABSTRACT: It has not been well established whether common indices of male condom failure are valid predictors of biologically meaningful exposure during condom use.
To address this gap, the authors compared self-reported condom malfunctions (i.e., breakage and slippage) and incorrect condom practices to 2 following objective measures of failure: prostate-specific antigen (PSA) detected in vaginal swabs collected after condom use and structural integrity of used condoms. The study, conducted in 2000-2001, evaluated 635 male condoms used by 77 women attending an outpatient, reproductive-health clinic in Birmingham, AL.
Women reported breakage or slippage for 7.9% of condoms; 3.5% of postcoital swabs had moderate or high levels of PSA; and laboratory testing of used condoms revealed breaks (1.1%) and leaks (2.0%). Self-reported breakage and slippage was associated with moderate/high PSA concentrations in postcoital swabs only when the malfunctions were not accompanied by reports of corrective actions to reduce exposure (adjusted odds ratio [aOR], 6.9; 95% confidence interval [CI], 1.8-26.2). Defects observed in postcoital laboratory testing were related to PSA detection (aOR, 8.0; 95% CI, 1.5-42.6). Incorrect practices defined on the condom label were frequent, but not all types were associated with semen exposure. Furthermore, other practices not currently label-defined were associated with semen exposure: touching the tip of the penis with his hands (aOR, 6.2; 95% CI, 2.3-17.0) or with her hands (aOR, 2.8; 95% CI, 1.1-72) before donning the condom.
Used correctly, male condoms afforded good protection based on objective measures of failure.
Sexually transmitted diseases 01/2011; 38(7):580-6. · 2.58 Impact Factor
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ABSTRACT: Research on the determinants of condom use and condom non-use generally has relied on self-reported data with questionable validity. We identified predictors of recent, unprotected sex among 331 female sex workers in Madagascar using two outcome measures: self-reports of unprotected sex within the past 48 h and detection of prostate-specific antigen (PSA), a biological marker of recent semen exposure. Multivariable logistic regression revealed that self-reported unprotected sex was associated with three factors: younger age, having a sipa (emotional partner) in the prior seven days, and no current use of hormonal contraception. The sole factor related to having PSA detected was prevalent chlamydial infection (adjusted odds ratio, 4.5; 95% confidence interval, 2.0-10.1). Differences in predictors identified suggest that determinants of unprotected sex, based on self-reported behaviors, might not correlate well with risk of semen exposure. Caution must be taken when interpreting self-reported sexual behavior measures or when adjusting for them in analyses evaluating interventions for the prevention of HIV/STIs.
AIDS and Behavior 12/2010; 14(6):1279-86. · 3.49 Impact Factor
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ABSTRACT: Although HPV 16 is the most common HPV genotype associated with cancerous lesions of the cervix, only a fraction of HPV 16 infected women are diagnosed with precancerous lesions of the cervix. Therefore, molecular changes in HPV 16, rather than infections per se, may serve as better screening or diagnostic biomarkers. The purpose of the study was to evaluate whether methylation status of specific regions of the HPV E6 gene promoter and enhancer is independently associated with the likelihood of being diagnosed with higher grades of cervical intraepithelial neoplasia (CIN 2+).
The study included 75 HPV 16-positive women diagnosed with CIN 2+ or ≤CIN 1. Pyrosequencing technology was applied to quantify methylation at 6 cytosine guanine dinucleotide (CpG) sites of the HPV 16 E6 promoter and enhancer. CIN 2+ (yes/no) was the dependent variable in logistic regression models that specified the degree of methylation of the CpG sites of the HPV 16 E6 gene as the primary independent predictors. All models were adjusted for demographic, lifestyle, known risk factors for cervical cancer, and circulating concentrations of "cancer-protective" micronutrients.
The odds of being diagnosed with CIN 2+ were 79% lower when the degree of methylation of the HPV 16 enhancer and promoter sites was ≥9.5% (OR = 0.21; 95% CI, 0.06-0.79; P = .02).
Results suggested that CpG methylation is independently involved in the biology of HPV 16 as well as in the development of higher grades of CIN.
Cancer 10/2010; 117(5):957-63. · 4.77 Impact Factor
