Anticipated pain as a predictor of discomfort with intrauterine device placement.

BACKGROUND: Intrauterine devices have been gaining popularity for the past 2 decades. Current data report that >10% of women who use contraception are using an intrauterine device. With <1% failure rates, the intrauterine device is one of the most effective forms of long-acting reversible contraception, yet evidence shows that fear of pain during intrauterine device placement deters women from choosing an intrauterine device as their contraceptive method. OBJECTIVES: The objective of this analysis was to estimate the association between anticipated pain with intrauterine device placement and experienced pain. We also assessed other factors associated with increased discomfort during intrauterine device placement. We hypothesized that patients with higher levels of anticipated pain would report a higher level of discomfort during placement. STUDY DESIGN: We performed a secondary analysis of the Contraceptive CHOICE Project. There were 9256 patients enrolled in Contraceptive CHOICE Project from the St. Louis region from 2007-2011; data for 1149 subjects who came for their first placement of either the original 52-mg levonorgestrel intrauterine system or the copper intrauterine device were analyzed in this study. Patients were asked to report their anticipated pain before intrauterine device placement and experienced pain during placement on a 10-point visual analog scale. We assessed the association of anticipated pain, patient demographics, reproductive characteristics, and intrauterine device type with experienced pain with intrauterine device placement. RESULTS: The mean age of Contraceptive CHOICE Project participants in this subanalysis was 26 years. Of these 1149 study subjects, 44% were black, and 53% were of low socioeconomic status. The median expected pain score was 5 for both the levonorgestrel intrauterine system and the copper intrauterine device; the median experienced pain score was 5 for the levonorgestrel intrauterine system and 4 for the copper intrauterine device. After we controlled for parity, history of dysmenorrhea, and type of intrauterine device, higher anticipated pain was associated with increased experienced pain (adjusted relative risk for 1 unit increase in anticipated pain, 1.19; 95% confidence interval, 1.14-1.25). Nulliparity, history of dysmenorrhea, and the hormonal intrauterine device (compared with copper) also were associated with increased pain with intrauterine device placement. CONCLUSION: High levels of anticipated pain correlated with high levels of experienced pain during intrauterine device placement. Nulliparity and a history of dysmenorrhea were also associated with greater discomfort during placement. This information may help guide and treat patients as they consider intrauterine device placement. Future research should focus on interventions to reduce preprocedural anxiety and anticipated pain to potentially decrease discomfort with intrauterine device placement.

Short Interpregnancy Intervals: Results from the First Baby Study.

BACKGROUND: Short interpregnancy interval (SIPI), defined as 18 months or fewer between delivery and subsequent conception, has become an independent marker of maternal and child health. METHODS: We performed a secondary analysis of 18 months of data from The First Baby Study, a prospective cohort of women followed from pregnancy through 3 years after their first birth. Women with SIPIs by 6, 6 to 12, and 12 to 18 months were compared with those without conceptions at those times. We then analyzed pregnancy intention of the subpopulation of women with a SIPI of 18 months or fewer. Logistic regression analyses determined associations between maternal characteristics, including sociodemographic and reproductive indicators, and SIPI incidence and intention. FINDINGS: Of 3,006 participants, 795 (26.5%) had a repeat pregnancy within 18 months: 58 (1.9%) occurred within 6 months, 242 (8.1%) between 6 and 12 months, and 495 (16.5%) between 12 and 18 months. Incidence of SIPI at each interval differed by maternal characteristics, including income, marital status, and intention. Most women (84%) with a SIPI of 6 months or less classified them as unintended. Less than 2% of women with SIPIs of 18 months or fewer reported any contraceptive use in the postpartum period and no pregnancies occurred with the use of very effective methods, including long-acting reversible contraception. CONCLUSIONS: The population of women at risk for SIPI is not homogenous. Among those with SIPIs, there is a stark contrast in intention between those who conceive early (≤6 months) versus later (≥12 months). Given that almost no pregnancies occurred when women used postpartum contraception, contraceptive counseling and unfettered access should be available for those at greatest risk for an early, repeat, unintended pregnancy.

Embryological exposure to valproic acid disrupts morphology of the deep cerebellar nuclei in a sexually dimorphic way.

Autism spectrum disorders (ASD) is diagnosed in males at a much higher rate than females. For this reason, the majority of autism research has used male subjects exclusively. However; more recent studies using genetic sex as a factor find that the development of the male and female brain is differentially affected by ASD. That is, the natural sex-specific differences that exist between male and female brains lead to sexually dimorphic expressions of autism. Here we investigate the putative sexual dimorphism that exists in the deep cerebellar nuclei of male and female rats exposed to valproic acid (VPA) on embryological day 12.5. We find natural sex-specific differences in adult nucleus area, length, and estimated cell populations. Therefore VPA exposure during embryology creates some sex-specific deficits such as higher cell counts in the VPA males and lower cell counts in the VPA females. At the same time, some effects of VPA exposure occur regardless of sex. That is, smaller nucleus area and length lead to truncated nuclei in both VPA males and females. These deficits are more pronounced in the VPA males suggesting that genetic sex could play a role in teratogenic susceptibility to VPA. Taken together our results suggests that VPA exposure induces sexually dimorphic aberrations in morphological development along a mediolateral gradient at a discrete region of the hindbrain approximate to rhombomere (R) 1 and 2. Sex-specific disruption of the local and long-range projections emanating from this locus of susceptibility could offer a parsimonious explanation for the brain-wide neuroanatomical variance reported in males and females with ASD.

Academic outcomes in childhood-onset systemic lupus erythematosus.

OBJECTIVE: To explore academic outcomes in childhood-onset systemic lupus erythematosus (cSLE) and their relationship to variables such as demographic and socioeconomic status, neurocognitive functioning, behavioral/emotional adjustment, and cSLE disease status. METHODS: Forty pairs of children diagnosed with cSLE and healthy best friend controls were rated by parents on a standardized scale of school competence. Information about participants' demographic and socioeconomic status was obtained, along with measures of cSLE disease activity and damage. All of the participants received formal neurocognitive testing and were also rated on standardized scales of behavioral/emotional adjustment and executive functioning. RESULTS: Compared to healthy controls, school competence was rated as lower in the cSLE group, although the groups did not differ significantly on indices of cognitive, behavioral, emotional, or executive functioning. School competence ratings were correlated with reading and mathematics achievement test scores in both groups, and with ratings of mental self-regulation in the cSLE group. School competence ratings were correlated with measures of cSLE disease activity and treatment intensity. CONCLUSION: cSLE is associated with inferior parent-rated academic outcomes compared to those noted in demographically-matched peers, despite similar neurocognitive function. The adverse academic outcomes that distinguish children with cSLE from their demographically-matched peers appear to be mediated by SLE disease activity and treatment.

Pharmacokinetics and pharmacodynamics of mycophenolic acid and their relation to response to therapy of childhood-onset systemic lupus erythematosus.

OBJECTIVES: Mycophenolic acid (MPA) is the active form of mycophenolate mofetil (MMF), which is currently used off-label as immunosuppressive therapy in childhood-onset SLE (cSLE). The objectives of this study were to (1) characterize the pharmacokinetics (MPA-PK) and pharmacodynamics (MPA-PD) of MPA and (2) explore the relationship between MPA-PK and cSLE disease activity. METHODS: MPA-PK [area under the curve from 0-12 hours (AUC(0-12))] and MPA-PD [inosine-monophosphate dehydrogenase (IMPDH) activity] were evaluated in cSLE patients on stable MMF dosing. Change in SLE disease activity while on MMF therapy was measured using the British Isles Lupus Assessment Group (BILAG) index. RESULTS: A total of 19 AUC(0-12) and 10 IMPDH activity profiles were included in the analysis. Large interpatient variability in MPA exposure (AUC(0-12)) was observed (mean ± SE: 32 ± 4.2 mg h/L; coefficient of variation: 57%). Maximum MPA serum concentrations coincided with maximum IMPDH inhibition. AUC(0-12) and weight-adjusted MMF dosing were only moderately correlated (r = 0.56, P = 0.01). An AUC(0-12) of ≥30 mg h/L was associated with decreased BILAG scores while on MMF therapy (P = 0.002). CONCLUSION: Weight-adjusted MMF dosing alone does not reliably allow for the prediction of exposure to biologically active MPA in cSLE. Individualized dosing considering MPA-PK appears warranted as this allows for better estimation of immunologic suppression (IMPDH activity). Additional controlled studies are necessary to confirm that an MPA AUC(0-12) of at least 30 mg h/L is required for cSLE improvement.