Adolescents and Sexual Risk-Taking: The Interplay of Constraining Relationship Beliefs, Healthy Sex Attitudes, and Romantic Attachment Insecurity

Introduction: Although sexual exploration during adolescence may be perceived as normative, many adolescents who are sexually active are likely to engage in risky sexual behaviors detrimental to their well-being. The present study examined the influence of insecure attachment (anxious and avoidant dimensions), healthy sex attitudes, and constraining relationship beliefs on the following sexual risk indicators: age at first sex, number of sexual partners, condom use, length of time knowing sexual partners, seriousness of relationship, and frequency of sex. Methods: Cross-sectional data from two cohorts recruited one year apart for a five-year project were analyzed. Adolescents were public high school students from a Southern state in the USA (cohort 1: N = 878, 51.1% females, M = 16.50 years old; cohort 2: N = 759, 46.9% females, M = 15.78 years old). Results: Across both cohorts, healthy sex attitudes were related to having sex for the first time at an older age, having less sexual partners in a lifetime, and knowing one’s sexual partner longer. High scores on the avoidant attachment dimension were related to less commitment to the relationship. This dimension also was related to holding lower scores on healthy sex attitudes, which in turn was related to having more sexual partners and knowing one’s sexual partner for a shorter time. Although not replicated, higher endorsement of constraining relationship beliefs was associated with inconsistent condom use and greater sex frequency. Conclusion: Findings suggests that attachment insecurity, healthy sex attitudes, and constraining relationship beliefs work together to influence adolescent sexual risks

Simplification of the Finnegan Neonatal Abstinence Scoring System: Retrospective Study of Two Institutions in the USA

Objective To develop a simplified Finnegan Neonatal Abstinence Scoring System (sFNAS) that will highly correlate with scores ≥ 8 and ≥12 in infants being assessed with the FNAS. Design, setting and participants This is a retrospective analysis involving 367 patients admitted to two level IV neonatal intensive care units with a total of 40 294 observations. Inclusion criteria included neonates with gestational age ≥ 37 0/7 weeks, who are being assessed for neonatal abstinence syndrome (NAS) using the FNAS. Infants with a gestational age \u3c 37 weeks were excluded. Methods A linear regression model based on the original FNAS data from one institution was developed to determine optimal values for each item in the sFNAS. A backward elimination approach was used, removing the items that contributed least to the Pearson’s correlation. The sFNAS was then cross-validated with data from a second institution. Results Pearson’s correlation between the proposed sFNAS and the FNAS was 0.914. The optimal treatment cut-off values for the sFNAS were 6 and 10 to predict FNAS scores ≥ 8 and ≥ 12, respectively. The sensitivity and specificity of these cut-off values to detect FNAS scores ≥ 8 and ≥ 12 were 0.888 and 0.883 for a cut-off of 6, and 0.637 and 0.992 for a cut-off of 10, respectively. The sFNAS cross-validation resulted in a Pearson’s correlation of 0.908, sensitivity and specificity of 0.860 and 0.873 for a cut-off of 6, and 0.525 and 0.986 for a cut-off of 10, respectively. Conclusion The sFNAS has a high statistical correlation with the FNAS, and it is cross-validated for the assessment of infants with NAS. It has excellent specificity and negative predictive value for identifying infants with FNAS scores ≥ 8 and ≥ 12

Impact of mitochondrial alternative oxidase expression on the response of Nicotiana tabacum to cold temperature

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87094/1/j.1399-3054.2011.01471.x.pd

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Emotional and Social Cognitive Predictors of Sexual Risk Indicators among Adolescents in Committed and Noncommitted Partnerships

Introduction: Little is known about the risks of casual sexual partnerships during adolescence despite many adolescents having sex within noncommitted relationships. We applied theories of adult attachment, planned behavior, and problem behavior to examine emotional and social cognitive predictors of variability in sexual risk indicators among adolescents in committed and noncommitted partnerships. Method: Data were drawn from 801 adolescents (53.6% female; ages 14-20 (M = 16.25)) living in a southern state in the United States. Results: Findings showed that healthy sex attitudes were related to knowing one’s sexual partner longer; this association was stronger for females, particularly those in noncommitted sexual partnerships. Additionally, healthy sex attitudes predicted fewer sexual partners across adolescents, except for male adolescents in noncommitted sexual partnerships. Romantic attachment insecurity and constraining relationship beliefs had different associations with sexual risk indicators according to gender and relationship status. Conclusion: Findings contribute to current understanding of risks associated with adolescents\u27 sexual engagement and offer insights about adolescents’ casual sexual partnerships

Cost of non-alcoholic steatohepatitis in Europe and the USA: The GAIN study.

Non-alcoholic steatohepatitis (NASH) leads to cirrhosis and is associated with a substantial socioeconomic burden, which, coupled with rising prevalence, is a growing public health challenge. However, there are few real-world data available describing the impact of NASH. The Global Assessment of the Impact of NASH (GAIN) study is a prevalence-based burden of illness study across Europe (France, Germany, Italy, Spain, and the UK) and the USA. Physicians provided demographic, clinical, and economic patient information via an online survey. In total, 3,754 patients found to have NASH on liver biopsy were stratified by fibrosis score and by biomarkers as either early or advanced fibrosis. Per-patient costs were estimated using national unit price data and extrapolated to the population level to calculate the economic burden. Of the patients, 767 (20%) provided information on indirect costs and health-related quality of life using the EuroQOL 5-D (EQ-5D; n = 749) and Chronic Liver Disease Questionnaire - Non-Alcoholic Fatty Liver Disease (CLDQ-NAFLD) (n = 723). Mean EQ-5D and CLDQ-NAFLD index scores were 0.75 and 4.9, respectively. For 2018, the mean total annual per patient cost of NASH was €2,763, €4,917, and €5,509 for direct medical, direct non-medical, and indirect costs, respectively. National per-patient cost was highest in the USA and lowest in France. Costs increased with fibrosis and decompensation, driven by hospitalisation and comorbidities. Indirect costs were driven by work loss. The GAIN study provides real-world data on the direct medical, direct non-medical, and indirect costs associated with NASH, including patient-reported outcomes in Europe and the USA, showing a substantial burden on health services and individuals. There has been little research into the socioeconomic burden associated with non-alcoholic steatohepatitis (NASH). The GAIN study provides real-world data on the direct medical, direct non-medical, and indirect costs associated with NASH, including patient-reported outcomes in five European countries (UK, France, Germany, Spain, and Italy) and the USA. Mean total annual per patient cost of NASH was estimated at €2,763, €4,917, and €5,509 for the direct medical, direct non-medical, and indirect cost categories, respectively. [Abstract copyright: © 2020 The Author(s).

Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder mainly affecting females and is associated with mutations in MECP2, the gene encoding methyl CpG-binding protein 2. Mouse models suggest that recombinant human insulin-like growth factor 1 (IGF-1) (rhIGF1) (mecasermin) may improve many clinical features. We evaluated the safety, tolerability, and pharmacokinetic profiles of IGF-1 in 12 girls with MECP2 mutations (9 with RTT). In addition, we performed a preliminary assessment of efficacy using automated cardiorespiratory measures, EEG, a set of RTT-oriented clinical assessments, and two standardized behavioral questionnaires. This phase 1 trial included a 4-wk multiple ascending dose (MAD) (40–120 μg/kg twice daily) period and a 20-wk open-label extension (OLE) at the maximum dose. Twelve subjects completed the MAD and 10 the entire study, without evidence of hypoglycemia or serious adverse events. Mecasermin reached the CNS compartment as evidenced by the increase in cerebrospinal fluid IGF-1 levels at the end of the MAD. The drug followed nonlinear kinetics, with greater distribution in the peripheral compartment. Cardiorespiratory measures showed that apnea improved during the OLE. Some neurobehavioral parameters, specifically measures of anxiety and mood also improved during the OLE. These improvements in mood and anxiety scores were supported by reversal of right frontal alpha band asymmetry on EEG, an index of anxiety and depression. Our data indicate that IGF-1 is safe and well tolerated in girls with RTT and, as demonstrated in preclinical studies, ameliorates certain breathing and behavioral abnormalities.Rett Syndrome Foundation (Grant 2534)Autism Speaks (Organization) (Grant 5795)National Institutes of Health (U.S.) (Harvard Clinical and Translational Science Center, Grant 1 UL1 RR 025758-01)Boston Children’s Hospital (Translational Research Program)Boston Children’s Hospital (Intellectual and Developmental Disabilities Research Center P30 HD18655