Pain, fatigue, depressive symptoms and sleep disturbance in young adults with cerebral palsy

Purpose: Investigate pain, fatigue, depressive symptoms and sleep disturbance in young adults with cerebral palsy compared to references. Materials and methods: Young adults with cerebral palsy (n = 97, aged 21-34 years) and age-matched references from the general population (n = 190) rated pain using a numeric rating scale and fatigue, depressive symptoms, sleep disturbance and global health using Patient-Reported Outcomes Measurement Information System (R) short forms. Scores were compared between cerebral palsy subgroups and the reference population. Correlation coefficients and linear regression analyses assessed interrelationships of health issues and associations with global health. Results: Individuals with Gross Motor Function Classification System level I had less pain, fatigue and depressive symptoms, while individuals with levels II and III-V had more pain (53% and 56%, p <0.001) and those with levels III-V more fatigue (39%, p = 0.035) than references (pain: 26%, fatigue: 14%). Pain and fatigue were more interrelated (correlation coefficients: 0.71 vs. 0.41) and stronger associated with global mental health in individuals with cerebral palsy. Conclusions: Young adults with Gross Motor Function Classification System levels II-V report more pain and those with levels III-V report more fatigue than references. Pain and fatigue are highly interrelated and specifically relate to mental health in individuals with cerebral palsy

Level of Retinol Deposit and Cervical Cancer

Objective: To analyze level of retinol deposit sufficiency in the natural history of cervical cancer. Methods: Serum retinol level was measured by ELISA from peripheral blood of subjects with normal cervix, cleared and persistent high risk human papilloma virus (HR-HPV) subclinical infection, and cervical cancer who fulfilled the inclusion and exclusion criteria. The study was held in Dr. Cipto Mangunkusumo and Fatmawati Hospital, Jakarta, within 2 years (August 2013- 2015). Blood was taken twice, consisting of post-8-hour fasting blood and 2 hours after 6000 IU retinyl palmitate oral administration. Results: Of 47 total samples, sufficient level of retinol deposit in normal cervix, cleared and persistent HR-HPV subclinical infection, and cervical cancer group was 85.0% (reference), 75.0% (OR 1.89), 33.3% (OR 11.33), and 75% (OR 1.89); respectively. Statistically, there was no significant difference from sufficiency level of retinol deposit between normal cervix and clearance HR-HPV subclinical infection (p=0.628), normal cervix and persistent HR-HPV subclinical infection (p=0.078), normal cervix and cervical cancer (p=0.433), cervical cancer and clearance HR-HPV subclinical infection (p=1.000), cervical cancer and persistent HR-HPV subclinical infection (p=0.430), persistent and clearance HR-HPV subclinical infection group (p=0.740). Conclusion: This study proves that normal cervix group has the highest level of retinol deposit sufficiency; however, it cannot be stated that cervical cancer group has less sufficiency level. Persistent HR-HPV subclinical infection group has the lowest level of retinol deposit (OR 11.33). There is no association between sufficient level of retinol deposit and clearance of HR-HPV. [Indones J Obstet Gynecol 2017; 5-1: 46-54] Keywords: cervical cancer, HR-HPV clearance, retinol deposi

Continuous oral contraceptives versus long-term pituitary desensitization prior to IVF/ICSI in moderate to severe endometriosis:study protocol of a non-inferiority randomized controlled trial

STUDY QUESTIONS: The primary objective is to investigate if continuous use of oral contraceptives is non-inferior compared to long-term pituitary desensitization with a GnRH agonist prior to IVF/ICSI in patients with moderate to severe endometriosis with regard to treatment efficacy. Secondary objectives concern treatment safety and cost-effectiveness. WHAT IS KNOWN ALREADY: Long-term pituitary desensitization with a GnRH agonist for 3-6 months prior to IVF/ICSI improves clinical pregnancy rates in women suffering from endometriosis. However, discussion about this treatment strategy exists because of its uncomfortable side effects. Alternatively, IVF/ICSI pre-treatment with continuously administered oral contraceptives may offer fewer side-effects and lower (in)direct costs, as well as encouraging IVF outcomes in women with endometriosis. To date, these two different IVF/ICSI pre-treatment strategies in women with endometriosis have not been directly compared. STUDY DESIGN SIZE DURATION: An open-label, parallel two-arm randomized controlled multicenter trial is planned, including patients with moderate to severe endometriosis. To demonstrate an absolute difference of 13% (delta of 10% with non-inferiority margin of 3%) with a power of 80% 137 patients per group are sufficient. Taking into account a withdrawal of patients of 10% and a cancelation rate of embryo transfer after ovarian pick up of 10% (for instance due to fertilization failure), the sample size calculation is rounded off to 165 patients per group; 330 patients in total will be included. After informed consent, eligible patients will be randomly allocated to the intervention or reference group by using web based block randomization stratified per centre. Study inclusion is expected to be complete in 3-5 years. PARTICIPANTS/MATERIALS SETTING METHODS: The research population consists of patients with moderate to severe endometriosis (ASRM III/IV) who are scheduled for their first, second or third IVF/ICSI treatment attempt. Women aged over 41 years, younger than 18 years, with a known contraindication for the use of oral contraceptives and/or GnRH agonists or with severe male factor infertility will be excluded from participation. After informed consent patients are allocated to the intervention group (one-phase oral contraceptive continuously during three subsequent months) or the reference group (three Leuprorelin 3.75 mg i.m./s.c. depot injections during three subsequent months). Tibolon 2.5 mg can be given daily as add-back therapy in the reference group. After 3 months of pre-treatment the IVF/ICSI stimulation phase will be started. The primary outcome is live birth rate after fresh embryo transfer. Secondary outcomes are cumulative live birth rate after one IVF/ICSI treatment cycle (including fresh and frozen embryo transfers up to 15 months after randomization), ongoing pregnancy rate and time to pregnancy. In addition, treatment outcome parameters, adverse events, side-effects during the first 3 months, complications, recurrence of endometriosis (complaints), quality of life, patient preferences, safety and costs effectiveness will be reported. Measurements will be performed at baseline and at 3, 6, 9, 12 and 15 months after randomization. STUDY FUNDING/COMPETING INTERESTs: All authors have no conflict of interest related to this manuscript. The department of reproductive medicine of the Amsterdam UMC location VUmc has received several research and educational grants from Guerbet, Merck and Ferring not related to the submitted work. TRIAL REGISTRATION NUMBER: The trial is registered as the COPIE trial (Continuous use of Oral contraceptives as an alternative for long-term Pituitary desensitization with a GnRH agonist prior to IVF/ICSI in Endometriosis patients) in the Dutch Trial Register (Ref. No. NTR6357, http://www.trialregister.nl). TRIAL REGISTRATION DATE: 16 March 2017. DATE OF FIRST PATIENT’S ENROLMENT: Enrollment is planned for November 2018

Pain, fatigue, depressive symptoms and sleep disturbance in young adults with cerebral palsy

Purpose: Investigate pain, fatigue, depressive symptoms and sleep disturbance in young adults with cerebral palsy compared to references. Materials and methods: Young adults with cerebral palsy (n = 97, aged 21–34 years) and age-matched references from the general population (n = 190) rated pain using a numeric rating scale and fatigue, depressive symptoms, sleep disturbance and global health using Patient-Reported Outcomes Measurement Information System® short forms. Scores were compared between cerebral palsy subgroups and the reference population. Correlation coefficients and linear regression analyses assessed interrelationships of health issues and associations with global health. Results: Individuals with Gross Motor Function Classification System level I had less pain, fatigue and depressive symptoms, while individuals with levels II and III–V had more pain (53% and 56%, p < 0.001) and those with levels III–V more fatigue (39%, p = 0.035) than references (pain: 26%, fatigue: 14%). Pain and fatigue were more interrelated (correlation coefficients: 0.71 vs. 0.41) and stronger associated with global mental health in individuals with cerebral palsy. Conclusions: Young adults with Gross Motor Function Classification System levels II–V report more pain and those with levels III–V report more fatigue than references. Pain and fatigue are highly interrelated and specifically relate to mental health in individuals with cerebral palsy.Implications for rehabilitation Except for those in the highest level of motor function, young adults with cerebral palsy report higher levels of pain and fatigue compared to the general population of the same age. Pain and fatigue are strongly interrelated and associated with mental health in young adults with cerebral palsy. The present study recommends to monitor pain and fatigue in young adults with cerebral palsy with low levels of gross motor function. We advise rehabilitation professionals to consider combined treatment for both pain and fatigue

Development curves of communication and social interaction in individuals with cerebral palsy

Aim: To determine development curves of communication and social interaction from childhood into adulthood for individuals with cerebral palsy (CP). Method: This Pediatric Rehabilitation Research in the Netherlands (PERRIN)-DECADE study longitudinally assessed 421 individuals with CP, aged from 1 to 20 years at baseline, after 13 years (n=121 at follow-up). Communication and social interactions were assessed using the Vineland Adaptive Behavior Scales. We estimated the average maximum performance limit (level) and age at which 90% of the limit was reached (age90) using nonlinear mixed-effects modeling. Results: One-hundred individuals without intellectual disability were aged 21 to 34 years at follow-up (39 females, 61 males) (mean age [SD] 28y 5mo [3y 11mo]). Limits of individuals without intellectual disability, regardless of Gross Motor Function Classification System (GMFCS) level, approached the maximum score and were significantly higher than those of individuals with intellectual disability. Ages90 ranged between 3 and 4 years for receptive communication, 6 and 7 years for expressive communication and interrelationships, 12 and 16 years for written communication, 13 and 16 years for play and leisure, and 14 and 16 years for coping. Twenty-one individuals with intellectual disability were between 21 and 27 years at follow-up (8 females, 13 males) (mean age [SD] 24y 7mo [1y 8mo]). Individuals with intellectual disability in GMFCS level V showed the least favourable development, but variation between individuals with intellectual disability was large. Interpretation: Individuals with CP and without intellectual disability show developmental curves of communication and social interactions similar to typically developing individuals, regardless of their level of motor function. Those with intellectual disability reach lower performance levels and vary largely in individual development. What this paper adds: Communication and social interactions in individuals with cerebral palsy without intellectual disability develop similarly to typically developing individuals. Communication and social interactions of individuals with intellectual disability develop less favourably and show large variation

The ETS Family Member TEL Binds to Nuclear Receptors RAR and RXR and Represses Gene Activation

Retinoic acid receptor (RAR) signaling is important for regulating transcriptional activity of genes involved in growth, differentiation, metabolism and reproduction. Defects in RAR signaling have been implicated in cancer. TEL, a member of the ETS family of transcription factors, is a DNA-binding transcriptional repressor. Here, we identify TEL as a transcriptional repressor of RAR signaling by its direct binding to both RAR and its dimerisation partner, the retinoid x receptor (RXR) in a ligand-independent fashion. TEL is found in two isoforms, created by the use of an alternative startcodon at amino acid 43. Although both isoforms bind to RAR and RXR in vitro and in vivo, the shorter form of TEL represses RAR signaling much more efficiently. Binding studies revealed that TEL binds closely to the DNA binding domain of RAR and that both Helix Loop Helix (HLH) and DNA binding domains of TEL are mandatory for interaction. We have shown that repression by TEL does not involve recruitment of histone deacetylases and suggest that polycomb group proteins participate in the process

Age-related natural fertility outcomes in women over 35 years : a systematic review and individual participant data meta-analysis

STUDY FUNDING/COMPETING INTEREST(S) S.J.C. received funding from the University of Adelaide Summer Research Scholarship. B.W.M. is supported by a NHMRC Investigator grant (GNT1176437), B.W.M. reports consultancy for ObsEva, Merck, Merck KGaA, iGenomix and Guerbet. B.W.M. reports research support by Merck and Guerbet.Peer reviewedPostprin

Childhood factors predict participation of young adults with cerebral palsy in domestic life and interpersonal relationships: a prospective cohort study

Purpose: To determine childhood predictors of participation in domestic life and interpersonal relationships of young adults with cerebral palsy (CP). Materials and methods: This 13-year follow-up of an existing cohort (baseline age 9–13 years) included 67 young adults with CP (age 21–27 years). The Vineland adaptive behavior scales (VABS) and Life Habits questionnaire were used to assess attendance and difficulty in participation in domestic life and interpersonal relationships. Baseline factors were categorised according to the international classification of functioning, disability, and health. Stepwise multiple linear regression analyses determined significant predictors (p < 0.05). Results: Lower manual ability, intellectual disability (ID), epilepsy and lower motor capacity predicted decreased future participation in domestic life, and/or interpersonal relationships (explained variance R2 ¼ 67–87%), whereas no association was found with environmental and personal factors. Extending models with baseline fine motor skills, communication, and interpersonal relationships increased R2 to 79–90%. Conclusions: Childhood factors account for 79–90% of the variation in young adult participation in domestic life and interpersonal relationships of individuals with CP. Children with limited motor capacity, low manual ability, ID, or epilepsy are at risk for restrictions in participation in young adulthood. Addressing fine motor, communication, and social skills in paediatric rehabilitation might promote young adult participation

The randomised uterine septum transsection trial (TRUST) : Design and protocol

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