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Background: Steroid-avoidance protocols have gained popularity in pediatric kidney transplant recipients at low immunologic risk. The long-term safety of steroid avoidance in children with immunologic risk factors remains unknown., Methods: Pediatric kidney transplant recipients from 2004 to 2014 in the Organ Procurement and Transplantation Network database who received tacrolimus and mycophenolate immunosuppression were investigated. Propensity score matching was used to compare graft survival in 1624 children who received steroid avoidance with 1624 children who received steroid-based immunosuppression. The effect of steroid avoidance on graft failure among immunologic risk strata was estimated using Cox proportional hazards regression in this propensity score-matched cohort., Results: It was observed that 5-year graft survival was mildly improved in children receiving steroid avoidance (84.8% versus 81.2%, P = 0.03). This improvement in graft survival occurred in the first 2 years following transplant, when the hazard ratio (HR) for allograft failure in children receiving steroid avoidance was 0.62 [95% confidence interval (CI) 0.45-0.86]. In contrast, steroid avoidance was not associated with improved allograft survival during Years 2-10 following transplant (HR = 0.93; 95% CI 0.75-1.15). During this time period, HRs (95% CIs) for allograft failure within immunologic risk strata were not significantly different from the null value of 1: repeat kidney transplants, 1.84 (0.84-4.05); African-Americans, 1.02 (0.67-1.56); sensitized recipients, 1.24 (0.63-2.43); recipients of deceased donor kidneys, 1.02 (0.79-1.32); recipients of completely human leukocyte antigen-mismatched kidneys, 0.80 (0.47-1.37); and recipients with pretransplant glomerular disease, 0.94 (0.71-1.23)., Conclusions: In pediatric kidney transplant recipients receiving tacrolimus- and mycophenolate-based immunosuppression, steroid avoidance can be safely practiced in children with immunologic risk factors., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: The role of adjunct systemic corticosteroid therapy in children with community-acquired pneumonia (CAP) is not known. The objective was to determine the association between adjunct systemic corticosteroid therapy and treatment failure in children who received antibiotics for treatment of CAP in the outpatient setting., Methods: The study included a retrospective cohort study of children, aged 1-18 years, with a diagnosis of CAP who were managed at an outpatient practice affiliated with Geisinger Health System from January 1, 2008 to January 31, 2010. The primary exposure was the receipt of adjunct corticosteroid therapy. The primary outcome was treatment failure defined as a respiratory-associated follow-up within 14 days of diagnosis in which the participant received a change in antibiotic therapy. The probability of receiving adjunct systemic corticosteroid therapy was calculated using a matched propensity score. A multivariable conditional logistic regression model was used to estimate the association between adjunct corticosteroids and treatment failure., Results: Of 2244 children with CAP, 293 (13%) received adjunct corticosteroids, 517 (23%) had underlying asthma, and 624 (28%) presented with wheezing. Most patients received macrolide monotherapy for their CAP diagnosis (n = 1329; 59%). Overall, treatment failure was not associated with adjunct corticosteroid treatment (odds ratio [OR], 1.72; 95% confidence interval [CI], 0.93 and 3.19), but the association was statistically significant among patients with no history of asthma (OR, 2.38; 95% CI, 1.03 and 5.52), with no statistical association among patients with a history of asthma., Conclusion: Adjunct corticosteroid therapy was associated with treatment failure among children diagnosed with CAP who did not have underlying asthma., (© The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that modifies histone tails. To help elucidate the biological function of PRMT6 in vivo, we generated transgenic mice that ubiquitously express PRMT6 fused to the hormone-binding portion of the estrogen receptor (ER*). The ER*-PRMT6 fusion is unstable and cytoplasmic, but upon systemic treatment with tamoxifen, it becomes stabilized and translocates into the nucleus. As a result, a dramatic increase in the H3R2me2a histone mark is observed. We found that one consequence of induced ER*-PRMT6 activation is increased IL-6 levels. IL-6 expression is regulated by the nuclear factor-kappa B (NF-κB) transcription factor, and PRMT6 functions as a coactivator of this pathway. We show that PRMT6 directly interacts with RelA, and that its overexpression enhances the transcriptional activity of an ectopic NF-κB reporter and endogenously regulates NF-κB target genes. PRMT6 is recruited, by RelA, to selective NF-κB target promoters upon TNF-α stimulation. Moreover, ER*-PRMT6 activation causes RelA accumulation in the nucleus. In summary, we observe that PRMT6 is recruited to chromatin at selective NF-κB target promoters, where it likely impacts the histone code and/or methylates other chromatin-associated proteins to facilitate transcription., (© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.)

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.

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.

Challenges in the accurate measurement of sexual behavior in human immunodeficiency virus (HIV) prevention research are well documented and have prompted discussion about whether valid assessments are possible. Audio computer-assisted self-interviewing (ACASI) may increase the validity of self-reported behavioral data. In 2006-2007, Zimbabwean women participated in a randomized, cross-sectional study that compared self-reports of recent vaginal sex and condom use collected through ACASI or face-to-face interviewing (FTFI) with a validated objective biomarker of recent semen exposure (prostate-specific antigen (PSA) levels). Of 910 study participants, 196 (21.5%) tested positive for PSA, an indication of semen exposure during the previous 2 days. Of these 196 participants, 23 (11.7%) reported no sex in the previous 2 days, with no difference in reported sexual activity between interview modes (12.5% ACASI vs. 10.9% FTFI; Fisher's exact test: P = 0.72). In addition, 71 PSA-positive participants (36.2%) reported condom-protected vaginal sex only; their reports also indicated no difference between interview modes (33.7% ACASI vs. 39.1% FTFI; P = 0.26). Only 52% of PSA-positive participants reported unprotected sex during the previous 2 days. Self-report was a poor predictor of recent sexual activity and condom use in this study, regardless of interview mode, providing evidence that such data should be interpreted cautiously.

Background: Male circumcision has received international attention as an intervention for reducing HIV infection among high-risk heterosexual men; however, few US studies have evaluated its association with the risk of HIV infection., Methods: We analyzed visit records for heterosexual African American men who underwent HIV testing while attending sexually transmitted disease (STD) clinics in Baltimore, Maryland, from 1993 to 2000. We used multivariable binomial regression to evaluate associations between circumcision and the risk of HIV infection among visits by patients with known and unknown HIV exposure., Results: Overall, 1096 (2.7%) of 40,571 clinic visits yielded positive HIV test results. Among 394 visits by patients with known HIV exposure, circumcision was significantly associated with lower HIV prevalence (10.2% vs. 22.0%; adjusted prevalence rate ratio [PRR], 0.49 [95% confidence interval [CI], 0.26-0.93]). Conversely, among 40,177 visits by patients with unknown HIV exposure, circumcision was not associated with reduced HIV prevalence (2.5% vs. 3.3%; adjusted PRR, 1.00 [95% CI, 0.86-1.15]), and age >or=25 years old and diagnosis of ulcerative STD were associated with increased prevalence., Conclusions: Circumcision was associated with substantially reduced HIV risk in patients with known HIV exposure, suggesting that results of other studies demonstrating reduced HIV risk for circumcision among heterosexual men likely can be generalized to the US context.

Background: Prostate-specific antigen (PSA) in vaginal fluid indicates exposure to semen, and was used to assess condom effectiveness, although validity and reliability have not been fully evaluated. Our objective was to compare PSA in self-collected samples with samples collected by a nurse., Methods: We conducted two studies, each with 100 women aged 18-48 years. In the first, a nurse exposed each participant to her partner's semen (10, 100 and 1000 microl), and nurse and participant collected samples. In the second, each participant sampled before and after using two male condoms (MC) and two female condoms (FC); a nurse collected another sample afterwards., Results: PSA concentration increased with semen exposure, but was lower in nurse-collected samples. Both procedures were sensitive, almost 100% after exposure to 100-1000 microl of semen. PSA detection rates with MC and FC were 13% and 28% in self-collected samples, 8% and 9% in nurse-collected samples. Concordance between sample types was 93% with the MC (95% CI: 89%; 96%), 78% with the FC (95% CI: 72%; 84%). PSA decay between sampling times may explain higher values in self-collected samples., Conclusions: PSA is a highly sensitive surrogate endpoint for condom effectiveness studies. Self-collected and nurse-collected samples are equivalent, but sample collection timing is critical.

Background: Approximately 18% of multiple births in the USA result from assisted reproduction technology (ART). Although many studies comparing ART and naturally conceived twins report no difference in risks for perinatal outcomes, others report slight to moderate positive or protective associations., Methods: We selected twin deliveries with and without indication of ART from Massachusetts live birth-infant death records from 1997 to 2000 linked to the US ART surveillance system. The sample was restricted to deliveries by mothers with increased socioeconomic status, private health insurance and intermediate/plus prenatal care use. Our final sample included 1446 and 2729 ART and non-ART twin deliveries, respectively. Odds ratios (OR) for associations between ART and perinatal outcomes were adjusted for maternal demographic factors, smoking, prenatal care and hospital care level., Results: ART twin deliveries were less likely than non-ART to be very preterm (adjusted OR 0.75; 95% confidence interval 0.58-0.97) or include a very low birthweight (<1500 g) infant (0.75; 0.58-0.95) or infant death (0.55; 0.35-0.88). In stratified analyses, these findings were observed among primiparous deliveries, but there were no risk differences among multiparous ART and non-ART twin deliveries., Conclusions: ART treatment was not a risk factor for adverse perinatal outcome, and risks for several outcomes were somewhat lower among ART twin deliveries. Nonetheless, ART is strongly associated with twinning and twins remain a high-risk group, relative to singletons. Promoting singleton gestation in assisted conception is an important strategy for reducing adverse outcomes.

In this 2000-2001 study, the authors compared the effectiveness of the male latex condom and the female polyurethane condom by assessing frequency and types of mechanical failure and by evaluating semen exposure during use. Eligible women from Birmingham, Alabama, were randomly assigned to begin the study with 10 male condoms and then switch to 10 female condoms (n = 55), or vice versa (n = 53), and were trained to use both types. Data collection included questionnaires for each condom use and measurement of prostate-specific antigen in specimens of vaginal fluid taken before and after intercourse. Participants returned 700 male condoms and 678 female condoms, and they reported mechanical problems for 9% and 34%, respectively. Moderate-high postcoital prostate-specific antigen levels (> or = 22 ng/ml) were detected in 3.5% of male condom uses and 4.5% of female condom uses (difference = 1%, 95% confidence interval: -1.6, 3.7). Moderate-high prostate-specific antigen values (> or = 22 ng/ml) were more frequent with mechanical problems (male condom, 9.6%; female condom, 9.4%) but less frequent with other problems (3.0% and 0.9%) or correct use with no problems (2.7% and 2.5%). This study indicates that although mechanical problems are more common with the female condom than with the male condom, these devices may involve a similar risk of semen exposure. Objectively assessed semen exposure is associated with self-reported mechanical problems.

This analysis examined how unmeasured confounding affects estimates of the effectiveness of condoms in preventing sexually transmitted infections. Data were analyzed from a prospective cohort study of 1,122 female sexually transmitted disease clinic patients in Alabama (1992-1995), wherein participants were evaluated for sexually transmitted infections at six 1-month intervals. Associations between condom use and incident gonorrhea and chlamydia infection were compared between case-crossover and cohort analyses. In a case-crossover analysis of 228 follow-up visits ending in gonorrhea/chlamydia ("case intervals") and 743 self-matched follow-up visits not ending in gonorrhea/chlamydia ("noncase intervals") (183 women), consistent condom use without breakage or slippage was associated with significantly reduced risk of infection relative to nonuse (adjusted risk odds ratio = 0.49, 95% confidence interval: 0.26, 0.92). Conversely, a cohort analysis of 245 case intervals and 3,896 noncase intervals (919 women) revealed no significant reduction in infection risk from consistent use of condoms (adjusted risk odds ratio = 0.79, 95% confidence interval: 0.53, 1.17). Dose-response relations between the number of unprotected sex acts and infection were stronger in the case-crossover analysis (p for trend = 0.009) than in the cohort analysis (p for trend = 0.18). These findings suggest that epidemiologic studies confounded by unmeasured differences between condom users and nonusers underestimate condom effectiveness against these infections. The case-crossover method provides an additional technique for reducing unmeasured confounding in studies of condom effectiveness.

This analysis examined the importance of differential exposure to infected partners in epidemiologic studies of latex condom effectiveness for prevention of sexually transmitted infections. Cross-sectional, enrollment visit data were analyzed from Project RESPECT, a trial of counseling interventions conducted at five publicly funded US sexually transmitted disease clinics between 1993 and 1997. The association between consistent condom use in the previous 3 months and prevalent gonorrhea and chlamydia (Gc/Ct) was compared between participants known to have infected partners and participants whose partner infection status was unknown. Among 429 participants with known Gc/Ct exposure, consistent condom use was associated with a significant reduction in prevalent gonorrhea and chlamydia (30% vs. 43%; adjusted prevalence odds ratio = 0.42, 95% confidence interval: 0.18, 0.99). Among 4,314 participants with unknown Gc/Ct exposure, consistent condom use was associated with a lower reduction in prevalent gonorrhea and chlamydia (24% vs. 25%; adjusted prevalence odds ratio = 0.82, 95% confidence interval: 0.66, 1.01). The number of unprotected sex acts was significantly associated with infection when exposure was known (p for trend < 0.01) but not when exposure was unknown (p for trend = 0.73). Restricting analyses to participants with known exposure to infected partners provides a feasible and efficient mechanism for reducing confounding from differential exposure to infected partners in condom effectiveness studies.

The objective of this study was to assess how characteristics of the intercourse and the couple relate to semen exposure during use of the female condom. From 1996 to 1998, 210 women in Birmingham, Alabama, were trained to use the female condom and follow study procedures during a group session and individually practiced inserting the device. The outcome was semen exposure as defined by comparing pre- and postcoital prostate-specific antigen levels in vaginal fluid. Women who had high income levels had lower rates of semen exposure (odds ratio (OR) = 0.3, 95% confidence interval (CI): 0.2, 0.7), while those in a relationship of less than 2 years were at greater risk (OR = 2.4, 95% CI: 1.3, 4.1). Couples with a large disparity in vaginal fundus size and penis size were at increased risk of semen exposure (OR = 2.7, 95% CI: 1.2, 6.0). Engaging in very active intercourse also increased the risk (OR = 1.7, 95% CI: 1.1, 2.6). Thus, the protective effect of the female condom appears to be a function of user- and intercourse-specific characteristics. Future studies of male condom efficacy should focus on collecting detailed data about the users and characteristics of intercourse to predict failure accurately.

In 1996-1998, the authors measured prostate-specific antigen (PSA) in vaginal fluid to assess the frequency of female condom failure and to evaluate the association of self-reported failure with semen exposure. Women at low risk of sexually transmitted diseases (n = 210) were recruited in Birmingham, Alabama. They were trained to use the female condom, sample vaginal fluid before and after condom use, and complete forms to report problems during each use. Semen exposure was assessed by comparing pre- and postcoital PSA levels in vaginal fluid. A total of 175 women used 2,232 condoms. The rate of semen exposure ranged from 7% to 21% of condom uses, depending on the exposure criterion. Exposure was more likely (21-34%) and more intense (mean postcoital PSA, 24.7 ng/ml) if participants reported a mechanical problem versus other problems or no problems (exposure rate, 5-20% in both instances; mean postcoital PSA, 9.6 and 7.8 ng/ml, respectively). In logistic regression analyses for repeated measurements, user-reported problems accounted for less than 59% of the instances of semen exposure. The female condom prevented semen exposure in 79-93% of condom uses. Exposure was associated with user-reported problems but also occurred in their absence. Reported problems and semen exposure decreased with user experience.

A total of 417 lung cancer cases and 849 controls were interviewed on their life-long tobacco usage and their current intake of four food items rich in retinol or carotene. The study was a hospital-based case control where 'cases' were lung cancer patients diagnosed during the period 1979/80 at seven hospitals in the Lombardy region (90% pathologically confirmed) and controls were patients admitted to the same hospitals for causes unrelated to tobacco smoking (epithelial cancers being excluded from present analysis). Odds ratios (OR) have been computed for increasing frequencies of consumption of liver, cheese, carrots and leafy green vegetables, having controlled for the confounding effects of tobacco usage, residence and birthplace. Current smokers who did not consume carrots showed a three-fold risk of developing lung cancer compared with those who ate them more than once a week (OR = 2.9 less than p less than 0.01); the ORs for consumers in the categories of 1-2 and 3-4 times per month were 1.8 and 2.0 respectively, with a significant test for linear trend (p less than 0.01). Among ex-smokers or non-smokers, no decrease of lung cancer risk is evident associated with carrot consumption. An excess risk was also associated with low intake of green vegetables although it was not significant, while no excess risk was evident for non-consumers of liver and cheese. The effect of carrots is independent of histological type of lung cancer while the effect of green vegetables was confined to epidermoid carcinomas: low versus high intake group OR = 1.3.