Teens' perspectives on yoga as a treatment for stress and depression.

OBJECTIVE: To understand adolescents' experiences and attitudes toward yoga, with a particular focus on acceptability and feasibility of a yoga intervention for depressed adolescents. DESIGN: Qualitative analysis of data from three focus groups and eight individual interviews, for a total of 22 teen participants. SETTING: Outpatient setting in a psychiatric hospital in the U.S. MAIN OUTCOME MEASURES: Teens were asked about their own and their peers' attitudes toward, and experiences with, hatha yoga; reactions to a study-created yoga video; and opinions on class logistics. RESULTS: Teens had both positive and negative attitudes toward, and experiences with, hatha yoga. They commented on "who does yoga;" many responses suggested a limited group (e.g., moms; people with money and time). Participants agreed that yoga could be potentially beneficial for depressed or stressed teens. Self-consciousness while being in a yoga class was a major concern. Overall, teens reacted favorably to the study-created yoga video. Teens had varied opinions about class logistics including class duration and size. Teens cited barriers to class, such as transportation, as well as barriers to home yoga practice. CONCLUSIONS: Key points for developing a yoga class that might be appealing to depressed or stressed teens include: creating a class with variety that teens will find interesting; taking concrete steps to decrease teen self-consciousness; incorporating messages relevant for teens and consistent with yoga philosophy; and actively countering stereotypes about who practices yoga. Limitations of this study include the lack of data from male teens.

Pregnancy registry: three-year follow-up of children conceived from letrozole, clomiphene, or gonadotropins.

OBJECTIVE: To study the development of children conceived from non-IVF infertility treatments consisting of gonadotropins, clomiphene, or letrozole. DESIGN: Prospective cohort study. SETTING: U.S. academic health centers. PATIENT(S): Children of women with polycystic ovary syndrome who conceived with letrozole (LTZ) or clomiphene (CC) in the PPCOS II study or women with unexplained infertility (AMIGOS study) who conceived with LTZ, CC, or gonadotropin (GN). INTERVENTION(S): Longitudinal annual follow-up from birth to age 3. MAIN OUTCOME MEASURE(S): Scores from Ages and Stages Developmental Questionnaire (ASQ), MacArthur-Bates Communicative Development Inventory (MCDI), and annual growth. RESULT(S): One hundred eighty-five children from 160 families participated in at least one follow-up evaluation from the two infertility trials. Most multiple gestations in the follow-up study resulted from GN treatment (n = 14) followed by CC (n = 6) and LTZ (n = 3). There were no significant differences among the three groups at any time point with respect to abnormal scores on the ASQ. On the MCDI Words and Gestures, the LTZ group scored significantly higher than the GN group for most items (phrases, early gestures, later gestures, and total gestures). Children in the CC group scored significantly higher than the GN group for the later gestures and total gestures items. CONCLUSION(S): Differences in growth and cognitive developmental rates among children conceived with first-line infertility therapies, including LTZ, are relatively minor and likely due to differences in multiple pregnancy rates.

Quality of life after mandibulectomy: the impact of the resected subsite.

The purpose of this study was to identify the factors that impact the quality of life (QOL) scores of patients undergoing mandibulectomy. All patients with a diagnosis of an oral cavity neoplasm involving the mandible who underwent a mandibulectomy between January 1, 2000 and December 31, 2015 and completed a University of Washington QOL questionnaire (UW-QOL) were included in the study. Fifty-eight patients fulfilled all inclusion criteria and completed the UW-QOL questionnaire. Forty patients (69%) underwent a segmental mandibulectomy and 18 patients underwent a marginal mandibulectomy. Forty-eight patients (82.7%) had a free flap reconstruction. There was no significant difference in the QOL scores between patients who underwent a marginal or a segmental mandibulectomy. In contrast, patients who underwent symphysial resection reported significantly worse scores in various domains compared to patients with body or ramus segmental mandibulectomy. Patients who underwent a segmental mandibulectomy that included the symphysis had worse outcomes in chewing, recreation, health-related and social QOL domains compared to those whose mandibulectomy did not include the symphysis.

Gestational Weight Gain in Women With Polycystic Ovary Syndrome: A Controlled Study.

Context: Women with polycystic ovary syndrome (PCOS) have increased risk for pregnancy complications, possibly related to pre-existing obesity and excessive gestational weight gain (GWG). Objectives: To assess the contributions of diagnosis and preconception weight on GWG and perinatal outcomes. Research Design and Methods: Prospective cohort study of singleton pregnancies in PCOS (n = 164) and ovulatory controls (n = 176) from infertility treatment. Main Outcome Measures: GWG, birthweight, pregnancy complications. Results: From preconception baseline, normal-weight women with PCOS gained 2.3 pounds more during the first trimester (95% CI, 0.3 to 4.3; P = 0.02), and by the end of the second trimester, 4.2 pounds more than controls (95% CI, 0.7 to 7.7; P = 0.02). Women who were overweight with PCOS gained significantly more weight than did controls by the end of the second trimester (5.2 pounds; 95% CI, 0.2 to 10.2; P = 0.04), whereas women with obesity and PCOS and control women had similar weight gain throughout pregnancy. Within normal-weight, overweight, and obese groups, prevalence of pre-eclampsia and gestational diabetes did not differ between the PCOS and control groups, nor was there a difference in birthweight. Preconception body mass index (BMI) was significantly associated with GWG; for every 1-kg/m2 increase in preconception BMI, GWG decreased by 0.62 pounds (95% CI, -0.85 to -0.40; P < 0.001). Conclusions: Women with PCOS who are of normal weight or are overweight before conception experience more GWG than do ovulatory controls. Within normal-weight, overweight, and obese groups, rates of perinatal complications do not significantly differ between women with PCOS and controls. Preconception BMI is the strongest predictor of GWG.

An ANMS-NASPGHAN consensus document on esophageal and antroduodenal manometry in children.

BACKGROUND: Upper gastrointestinal symptoms in children are common and motility disorders are considered in the differential diagnosis. High resolution esophageal manometry (HRM) has revolutionized the study of esophageal physiology, and the addition of impedance has provided new insights into esophageal function. Antroduodenal motility has provided insight into gastric and small bowel function. PURPOSE: This review highlights some of the recent advances in pediatric esophageal and antroduodenal motility testing including indications, preparation, performance, and interpretation of the tests. This update is the second part of a two part series on manometry studies in children (first part was on anorectal and colonic manometry [Neurogastroenterol Motil. 2016;29:e12944]), and has been endorsed by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and the American Neurogastroenterology and Motility Society (ANMS).

Vaginal film for prevention of HIV: using visual and tactile evaluations among potential users to inform product design.

Topical prevention of HIV and other STIs is a global health priority. To provide options for users, developers have worked to design safe, effective and acceptable vaginal dissolving film formulations. We aimed to characterize user experiences of vaginal film size, texture and color, and their role in product-elicited sensory perceptions (i.e. perceptibility), acceptability and willingness to use. In the context of a user-centered product evaluation study, we elicited users' 'first impressions' of various vaginal film formulation designs via visual and tactile prototype inspection during a qualitative user evaluation interview. Twenty-four women evaluated prototypes. Participants considered size and texture to be important for easy insertion. Color was more important following dissolution than prior to insertion. When asked to combine and balance all properties to arrive at an ideal film, previously stated priorities for individual characteristics sometimes shifted, with the salience of some individual characteristics lessening when multiple characteristics were weighted in combination. While first impressions alone may not drive product uptake, users' willingness to initially try a product is likely impacted by such impressions. Developers should consider potential users' experiences and preferences in vaginal film design. This user-focused approach is useful for characterizing user sensory perceptions and experiences relevant to early design of prevention technologies.

Intra- and interrater reliability of the Chicago Classification of achalasia subtypes in pediatric high-resolution esophageal manometry (HRM) recordings.

BACKGROUND: Subtyping achalasia by high-resolution manometry (HRM) is clinically relevant as response to therapy and prognosis have shown to vary accordingly. The aim of this study was to assess inter- and intrarater reliability of diagnosing achalasia and achalasia subtyping in children using the Chicago Classification (CC) V3.0. METHODS: Six observers analyzed 40 pediatric HRM recordings (22 achalasia and 18 non-achalasia) twice by using dedicated analysis software (ManoView 3.0, Given Imaging, Los Angeles, CA, USA). Integrated relaxation pressure (IRP4s), distal contractile integral (DCI), intrabolus pressurization pattern (IBP), and distal latency (DL) were extracted and analyzed hierarchically. Cohen's κ (2 raters) and Fleiss' κ (>2 raters) and the intraclass correlation coefficient (ICC) were used for categorical and ordinal data, respectively. RESULTS: Based on the results of dedicated analysis software only, intra- and interrater reliability was excellent and moderate (κ=0.89 and κ=0.52, respectively) for differentiating achalasia from non-achalasia. For subtyping achalasia, reliability decreased to substantial and fair (κ=0.72 and κ=0.28, respectively). When observers were allowed to change the software-driven diagnosis according to their own interpretation of the manometric patterns, intra- and interrater reliability increased for diagnosing achalasia (κ=0.98 and κ=0.92, respectively) and for subtyping achalasia (κ=0.79 and κ=0.58, respectively). CONCLUSIONS: Intra- and interrater agreement for diagnosing achalasia when using HRM and the CC was very good to excellent when results of automated analysis software were interpreted by experienced observers. More variability was seen when relying solely on the software-driven diagnosis and for subtyping achalasia. Therefore, diagnosing and subtyping achalasia should be performed in pediatric motility centers with significant expertise.

Sexual function in infertile women with polycystic ovary syndrome and unexplained infertility.

BACKGROUND: While female sexual dysfunction is a frequent occurrence, characteristics in infertile women are not well delineated. Furthermore, the impact of infertility etiology on the characteristics in women with differing androgen levels observed in women with polycystic ovary syndrome and unexplained infertility has not been assessed. OBJECTIVE: The objective of the study was to determine the characteristics of sexual dysfunction in women with polycystic ovary syndrome and unexplained infertility. STUDY DESIGN: A secondary data analysis was performed on 2 of Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Networks clinical trials: Pregnancy in Polycystic Ovary Syndrome Study II and Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation. Both protocols assessed female sexual function using the Female Sexual Function Inventory and the Female Sexual Distress Scale. RESULTS: Women with polycystic ovary syndrome had higher weight and body mass index than women with unexplained infertility (each P < .001), greater phenotypic (Ferriman-Gallwey hirsutism score, sebum score, and acne score; each P < .001), and hormonal (testosterone, free testosterone, and dehydroepiandrosterone; each P < .001) evidence of androgen excess. Sexual function scores, as assessed by the Female Sexual Function Inventory, were nearly identical. The Female Sexual Distress Scale total score was higher in women with polycystic ovary syndrome. The mean Female Sexual Function Inventory total score increased slightly as the free androgen index increased, mainly as a result of the desire subscore. This association was more pronounced in the women with unexplained infertility. CONCLUSION: Reproductive-age women with infertility associated with polycystic ovary syndrome and unexplained infertility, despite phenotypic and biochemical differences in androgenic manifestations, do not manifest clinically significant differences in sexual function.

Pediatric rumination subtypes: A study using high-resolution esophageal manometry with impedance.

BACKGROUND: The differential diagnosis of intractable reflux in children includes rumination syndrome, but confirming the diagnosis using antroduodenal manometry is invasive, is costly, and requires anesthesia. High-resolution esophageal manometry with impedance (HRM-MII) overcomes these limitations, and the goal of this study is to validate the use of HRM-MII as a diagnostic tool for rumination and to describe the subtypes of pediatric rumination. METHODS: We reviewed the HRM-MII tracings of 21 children presenting with symptoms of intractable reflux in whom rumination was being considered. Patients underwent a standard and post-prandial HRM-MII. Peak intraluminal esophageal pressures, baseline gastric and thoracic pressures, and the timing of the R wave relative to LES relaxations and bolus flow were recorded. Chi-square analyses were used for comparison of proportions and means were compared using t-tests or non-parametric equivalent. KEY RESULTS: Forty-one (55.5%) primary and 33 (44.5%) secondary rumination episodes were seen. Three types of primary rumination were identified: i) LES relaxation without retrograde flow preceding the R wave (51% of episodes); ii) LES relaxation after the R wave (20% of episodes); and iii) R waves with no LES relaxation (29% of episodes). Eleven patients had rumination episodes with a peak gastric pressure <30 mm Hg. A total of 44 (60%) rumination episodes occurred during the standard HRM-MII, and 30 (40%) occurred during or after the meal. CONCLUSIONS & INFERENCES: HRM-MII can accurately diagnose rumination in children. We identify three types of primary rumination which may provide insight into therapeutic response.

Longitudinal associations between post-traumatic stress disorder and metabolic syndrome severity.

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated with elevated risk for metabolic syndrome (MetS). However, the direction of this association is not yet established, as most prior studies employed cross-sectional designs. The primary goal of this study was to evaluate bidirectional associations between PTSD and MetS using a longitudinal design. METHOD: A total of 1355 male and female veterans of the conflicts in Iraq and Afghanistan underwent PTSD diagnostic assessments and their biometric profiles pertaining to MetS were extracted from the electronic medical record at two time points (spanning ~2.5 years, n = 971 at time 2). RESULTS: The prevalence of MetS among veterans with PTSD was just under 40% at both time points and was significantly greater than that for veterans without PTSD; the prevalence of MetS among those with PTSD was also elevated relative to age-matched population estimates. Cross-lagged panel models revealed that PTSD severity predicted subsequent increases in MetS severity (ß = 0.08, p = 0.002), after controlling for initial MetS severity, but MetS did not predict later PTSD symptoms. Logistic regression results suggested that for every 10 PTSD symptoms endorsed at time 1, the odds of a subsequent MetS diagnosis increased by 56%. CONCLUSIONS: Results highlight the substantial cardiometabolic concerns of young veterans with PTSD and raise the possibility that PTSD may predispose individuals to accelerated aging, in part, manifested clinically as MetS. This demonstrates the need to identify those with PTSD at greatest risk for MetS and to develop interventions that improve both conditions.

Sexual dysfunction and its impact on quality of life in Chinese patients with schizophrenia treated in primary care.

PURPOSE: Sexual dysfunction in schizophrenia patients is common. In China, maintenance treatment for clinically stable patients with schizophrenia is usually provided by primary care physicians. Illness- or treatment-related sexual dysfunction in this patient population has been never studied. This study describes the prevalence and correlates of sexual dysfunction and its impact on quality of life (QOL) in patients with schizophrenia treated in primary care in China. METHOD: A total of 607 patients with schizophrenia treated in 22 randomly selected primary care services in China formed the study sample. Patients' socio-demographic and clinical characteristics including sexual function and QOL were recorded using a standardized protocol and data collection. RESULTS: Sexual dysfunction was present in 69.9% of all patients; 60.7% in males and 80.6% in females. Multiple logistic regression analysis revealed that female gender, being single, older age and use of first-generation antipsychotics were independently and significantly associated with more sexual dysfunction accounting for 23.5% of its variance (P<0.001). Unexpectedly, sexual dysfunction was not associated with lower QOL. CONCLUSIONS: High rate of sexual dysfunction was reported in the majority of patients with schizophrenia treated in primary care in China. Given its negative impact on social adjustment, QOL and treatment adherence, efforts should be made to address sexual dysfunction in this patient population.

Do baseline estrogen and testosterone affect lower urinary tract symptoms (LUTS) prior to or after pharmacologic treatment with tadalafil?

Little is known about how total testosterone and estradiol-17ß influence lower urinary tract symptoms (LUTS) in men with benign prostatic hypertrophy (BPH). We analyzed data from a subset of men aged ≥18 years randomized to tadalafil 5 mg once-daily or placebo who had ≥6 month history of LUTS and an International Prostate Symptom Score (IPSS)≥13 enrolled in one of three randomized, placebo-controlled tadalafil clinical trials (N = 958). Three specific aims were addressed, as follows: (i) To characterize enrolled men by treatment randomization and testosterone level; (ii) to assess cross-sectional associations of estradiol-17ß, testosterone, and LUTS prior to treatment with tadalafil; and, (iii) to assess longitudinal associations between baseline estradiol-17ß and testosterone and improvements or worsening of LUTS during a 12-week period of tadalafil or placebo administration. LUTS were assessed by total IPSS, IPSS voiding sub-score (IPSS-V) and IPSS storage sub-score (IPSS-S) for cross-sectional analyses, and change in total IPSS (ΔIPSS), ΔIPSS-V, and ΔIPSS-S between baseline and 12-week visit for longitudinal analyses. Correlation analyses and linear regression examined associations. Baseline testosterone was not significantly associated with IPSS. In contrast, estradiol-17ß was inversely correlated with IPSS (r = -0.08; p < 0.05) and IPSS-S (r = -0.14; p < 0.05). Tadalafil treatment resulted in greater IPSS improvements in men with lower baseline estradiol-17ß versus those with higher baseline estradiol-17ß. Lower baseline estradiol-17ß was significantly associated with modestly improved ΔIPSS-V (p = 0.04) and Δtotal IPSS (p = 0.05) but not with ΔIPSS-S, following treatment which may substantiate the role of bladder dysfunction because of nerve and smooth muscle changes in the bladder in addition to benign prostatic enlargement in LUTS. Circulating baseline testosterone did not predict ΔIPSS. Men with lower baseline estradiol-17ß levels showed greater responsiveness to tadalafil 5 mg treatment than those with higher baseline estradiol-17ß levels when responsiveness was measured using total IPSS and IPSS-V.

Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility.

BACKGROUND: The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates. METHODS: We enrolled couples with unexplained infertility in a multicenter, randomized trial. Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were randomly assigned to ovarian stimulation (up to four cycles) with gonadotropin (301 women), clomiphene (300), or letrozole (299). The primary outcome was the rate of multiple gestations among women with clinical pregnancies. RESULTS: After treatment with gonadotropin, clomiphene, or letrozole, clinical pregnancies occurred in 35.5%, 28.3%, and 22.4% of cycles, and live birth in 32.2%, 23.3%, and 18.7%, respectively; pregnancy rates with letrozole were significantly lower than the rates with standard therapy (gonadotropin or clomiphene) (P=0.003) or gonadotropin alone (P<0.001) but not with clomiphene alone (P=0.10). Among ongoing pregnancies with fetal heart activity, the multiple gestation rate with letrozole (9 of 67 pregnancies, 13%) did not differ significantly from the rate with gonadotropin or clomiphene (42 of 192, 22%; P=0.15) or clomiphene alone (8 of 85, 9%; P=0.44) but was lower than the rate with gonadotropin alone (34 of 107, 32%; P=0.006). All multiple gestations in the clomiphene and letrozole groups were twins, whereas gonadotropin treatment resulted in 24 twin and 10 triplet gestations. There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications. CONCLUSIONS: In women with unexplained infertility, ovarian stimulation with letrozole resulted in a significantly lower frequency of multiple gestation but also a lower frequency of live birth, as compared with gonadotropin but not as compared with clomiphene. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01044862.).

Rural vs. urban disparities in association with lower urinary tract symptoms and benign prostatic hyperplasia in ageing men, NHANES 2001-2008.

OBJECTIVE: The objective of this study was to investigate rural/urban and socio-demographic disparities in lower urinary tract symptoms and benign prostatic hyperplasia (LUTS/BPH) in a nationally representative population of men. METHODS: Data on men age ≥40 years (N = 4,492) in the 2001-2008 National Health and Nutrition Examination Surveys were analysed. Self-report of physician-diagnosed enlarged prostate and/or BPH medication use defined recognised LUTS/BPH. Urinary symptoms without BPH diagnosis/medications defined unrecognised LUTS/BPH. Rural-Urban Commuting Area Codes assessed urbanisation. Unadjusted and multivariable associations (odds ratios (OR)) between LUTS/BPH and covariates were calculated using logistic regression. RESULTS: Recognised and unrecognised LUTS/BPH weighted-prevalence estimates were 16.5% and 9.6%. There were no significant associations between LUTS/BPH and rural/urban status. Significant predisposing factors for increased adjusted odds of recognised and unrecognised LUTS/BPH included age, hypertension (OR=1.4;1.4), analgesic use (OR=1.4;1.4) and PSA level >4 ng/mL (OR=2.3;1.9) when adjusted for rural/urban status, race, education, income, alcohol, health insurance, health care and proton pump inhibitor (PPI) use (all p ≤ 0.1). Restricting to urban men only (N = 3,371), healthcare use (≥4visits/year) and PPI's increased adjusted odds of recognised LUTS/BPH (OR=2.0;1.6); no health insurance and

Comparison of Macular Thickness in Patients with Keratoconus and Control Subjects Using the Cirrus HD-OCT.

PURPOSE: The aim of the present study was to compare macular thickness in patients with keratoconus (KC) with macular thickness in healthy subjects. SUBJECTS AND METHODS: Twenty-six patients with KC and 52 control subjects were included. The macular structure was evaluated using a Zeiss Cirrus HD-OCT. The scan pattern used was 512 × 128, which covers an area of approximately 6 × 6 mm of the retina. The cube volume was assessed as well as macular thickness in each of the 9 sectors defined by the software. RESULTS: The mean signal strength was significantly lower in the KC group (mean 8.4, range 6-10) compared with the control group (mean 9.7, range 7-10), P < 0.0001 (unpaired t-test). There were no significant differences in cube volume (unpaired t-test), cube average thickness, or macular thickness between the KC group and the control subjects in any of the retinal locations (one-way ANOVA). CONCLUSION: Macular structure as measured by OCT in KC subjects should be expected to lie within the range of age and sex matched controls.

Assessment of multiple intrauterine gestations from ovarian stimulation (AMIGOS) trial: baseline characteristics.

OBJECTIVE: To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications. DESIGN: Randomized, prospective clinical trial. SETTING: Multicenter university-based clinical practices. PATIENT(S): A total of 900 couples with unexplained infertility. INTERVENTION(S): Collection of baseline demographics, blood samples, and ultrasonographic assessments. MAIN OUTCOME MEASURE(S): Demographic, laboratory, imaging, and survey characteristics. RESULT(S): Demographic characteristics of women receiving clomiphene citrate (CC), letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7 ± 25.7 months, with 59% primary infertility. More than one-third of the women were current or past smokers. The mean body mass index (BMI) was 27 and mean antimüllerian hormone level was 2.6; only 11 women (1.3%) had antral follicle counts of <5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners. CONCLUSION(S): The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, antimüllerian hormone levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment groups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and CC treatment. CLINICAL TRIAL REGISTRATION NUMBER: NCT 01044862.

Female sexual function improved with ospemifene in postmenopausal women with vulvar and vaginal atrophy: results of a randomized, placebo-controlled trial.

BACKGROUND: Ospemifene is a non-estrogen, tissue selective estrogen receptor agonist/antagonist, or selective estrogen receptor modulator, recently approved for the treatment of dyspareunia, a symptom of vulvar and vaginal atrophy (VVA), due to menopause. Postmenopausal dyspareunia is often associated with female sexual dysfunction (FSD). In this report, we present data that demonstrate the effect of ospemifene 60 mg/day on FSD assessed by the Female Sexual Function Index (FSFI), a widely used tool with six domains (Arousal, Desire, Orgasm, Lubrication, Satisfaction, and Pain). METHODS: A phase-3, randomized, double-blind, 12-week trial (n = 919) compared the efficacy and safety of oral ospemifene 60 mg/day vs. placebo in postmenopausal women with VVA in two strata based on self-reported, most bothersome symptom of either dyspareunia or dryness. Primary data were published previously. We report herein pre-specified secondary efficacy endpoints analyses, including changes from baseline to Weeks 4 and 12 for FSFI total and domain scores as well as serum hormone levels. RESULTS: Ospemifene 60 mg/day demonstrated a significantly greater FSFI total score improvement vs. placebo at Week 4 (p < 0.001). Improvement in FSFI scores continued to Week 12 (p < 0.001). At Week 4, the FSFI domains of Sexual Pain, Arousal, and Desire were significantly improved with ospemifene vs. placebo; at Week 12, improvements in all domains were significant (p < 0.05). Changes in serum hormones were minor and uncorrelated with changes in sexual functioning. CONCLUSION: In a large, randomized, double-blind, placebo-controlled trial, ospemifene 60 mg/day significantly improved FSD in women with VVA. Consistent effects across FSFI domains were observed.

Inter- and intrarater reliability of the Chicago Classification in pediatric high-resolution esophageal manometry recordings.

BACKGROUND: The Chicago Classification (CC) facilitates interpretation of high-resolution manometry (HRM) recordings. Application of this adult based algorithm to the pediatric population is unknown. We therefore assessed intra and interrater reliability of software-based CC diagnosis in a pediatric cohort. METHODS: Thirty pediatric solid state HRM recordings (13M; mean age 12.1 ± 5.1 years) assessing 10 liquid swallows per patient were analyzed twice by 11 raters (six experts, five non-experts). Software-placed anatomical landmarks required manual adjustment or removal. Integrated relaxation pressure (IRP4s), distal contractile integral (DCI), contractile front velocity (CFV), distal latency (DL) and break size (BS), and an overall CC diagnosis were software-generated. In addition, raters provided their subjective CC diagnosis. Reliability was calculated with Cohen's and Fleiss' kappa (κ) and intraclass correlation coefficient (ICC). KEY RESULTS: Intra- and interrater reliability of software-generated CC diagnosis after manual adjustment of landmarks was substantial (mean κ = 0.69 and 0.77 respectively) and moderate-substantial for subjective CC diagnosis (mean κ = 0.70 and 0.58 respectively). Reliability of both software-generated and subjective diagnosis of normal motility was high (κ = 0.81 and κ = 0.79). Intra- and interrater reliability were excellent for IRP4s, DCI, and BS. Experts had higher interrater reliability than non-experts for DL (ICC = 0.65 vs ICC = 0.36 respectively) and the software-generated diagnosis diffuse esophageal spasm (DES, κ = 0.64 vs κ = 0.30). Among experts, the reliability for the subjective diagnosis of achalasia and esophageal gastric junction outflow obstruction was moderate-substantial (κ = 0.45-0.82). CONCLUSIONS & INFERENCES: Inter- and intrarater reliability of software-based CC diagnosis of pediatric HRM recordings was high overall. However, experience was a factor influencing the diagnosis of some motility disorders, particularly DES and achalasia.

The sensitivity of acoustic cough recording relative to intraesophageal pressure recording and patient report during reflux testing.

BACKGROUND: One of the primary indications for reflux testing with multichannel intraluminal impedance with pH (pH-MII) is to correlate reflux events with symptoms such as cough. Adult and pediatric studies have shown, using cough as a model, that patient report of symptoms is inaccurate. Unfortunately, intraesophageal pressure recording (IEPR) to record coughs is more invasive which limits its utility in children. The primary aim of this study was to validate the use of acoustic cough recording (ACR) during pH-MII testing. METHODS: We recruited children undergoing pH-MII testing for the evaluation of cough. We simultaneously placed IEPR and pH-MII catheters and an ACR device in each patient. Each 24 h ACR, pH-MII, and IEPR tracing was scored by blinded investigators. Sensitivities for each method of symptom recording were calculated. KEY RESULTS: A total of 2698 coughs were detected; 1140 were patient reported PR, 2425 were IEPR detected, and 2400 were ACR detected. The sensitivity of PR relative to ACR was 45.9% and the sensitivity of IEPR relative to ACR was 93.6%. There was strong inter-rater reliability (κ = 0.78) for the identification of cough by ACR. CONCLUSIONS & INFERENCES: Acoustic recording is a non-invasive, sensitive method of recording cough during pH-MII testing that is well suited for the pediatric population.

Application and interpretation of genome-wide association (GWA) studies for informing pharmacogenomic research - examples from the field of age-related macular degeneration.

Genome-wide association (GWA) studies apply broad DNA scans on hundreds-of-thousands of common sequence variants in thousands of people for the purpose of mapping trait- or disease-related loci. We provide examples of ligand- and target-based studies from the field of age-related macular degeneration (AMD) to demonstrate the value of the GWA approach in confirmatory and exploratory pharmacogenomics research. Complementing this genomic analysis, we used a simple biochemical retinal pigment epithelium (RPE) oxidative, apoptotic high throughput screening (HTS) assay to identify compounds. This ligand-to-targetto DNA sequence variant-to disease approach provided guidance on rational design of preclinical studies and identified associations between: 1) valproic acid and advanced AMD-associated genes with the capacity to alter GABA-succinate signaling (ALDH5A1, CACNA1C, SUCLA2, and GABBR2) and chromatin remodeling (HDAC9); and 2) Ropinirole and a geographic atrophy-associated gene (DRD3) with the capacity to alter systems involved in cAMP-PKA signaling. In both applications of our method, the breadth of GWA findings allowed efficient expansion of results to identify enriched pathways and additional ligands capable of targeting pathway constituents. A disease associated SNP-to gene-to target-to ligand approach provided guidance to inform preventive and therapeutic preclinical studies investigating roles of targets in: 1) PPAR-RXR transcription complex constituents for neovascular AMD; and 2) the stress activated MAPK signaling cascade constituents for advanced AMD. Our conclusion is that publically available data from GWA studies can be used successfully with open-access genomics, proteomics, structural chemistry, and pharmacogenomics databases in an efficient, rational approach to streamline the processes of planning and implementation for confirmatory and exploratory pre-clinical studies of preventive or therapeutic pharmacologic treatments for complex diseases.