Low-dose AtropIne for Myopia Control in Children (AIM): protocol for a randomised, controlled, double-blind, multicentre, clinical trial with two parallel arms.

INTRODUCTION: Myopia is a major cause of degenerative eye disease and increases the risk of secondary visual impairment. Mitigating its progression therefore has great potential of clinically relevant benefit as shown by using highly diluted atropine eye drops in children of Asian origin. However, limited evidence is available regarding the efficacy and safety of low-dose atropine therapy in non-Asian populations. Hence, the Low-dose AtropIne for Myopia Control in Children (AIM) study will test the efficacy and safety of 0.02% atropine vs placebo in a German population. METHODS AND ANALYSIS: AIM is a national, multicentre, prospective, randomised, placebo-controlled, double-blind trial with two parallel arms. The primary objective is to assess the efficacy of atropine 0.02% eyedrops for myopia control in children of Caucasian origin. The primary outcome is the change in cycloplegic refraction after 1 year of treatment (D/year). Secondary and tertiary outcome measures comprise the change in axial length (mm/year) in children treated with 0.02% atropine compared with placebo, the myopic progression of participants treated with 0.01% compared with 0.02% atropine (D/year and mm/year), and the safety profile of both 0.02% and 0.01% atropine. Furthermore, the myopic progression 1 year after cessation of therapy with 0.02% atropine will be evaluated. Inclusion criteria are an age of 8-12 years and myopia of -1 D to -6 D with an estimated annual myopia progression of ≥0.5 D. After randomisation, patients will receive either atropine 0.02% (arm A) or placebo eye drops (arm B) in the first year of treatment. In the second year, they will continue to receive atropine 0.02% (arm A) or switch to atropine 0.01% (arm B). In the third year, they will switch to placebo (arm A) or continue with atropine 0.01% (arm B). To achieve a statistical power of 80%, the calculated sample size is 300. The trial has started in October 2021 with a planned recruitment period of 18 months. ETHICS AND DISSEMINATION: AIM has been approved by the Central Ethics Committee of the University Medical Center Freiburg (21-1106), local ethics committees of each participating centre and the German Federal Institute for Drugs and Medical Devices (61-3910-4044659). It complies with the Declaration of Helsinki, local laws and ICH-GCP. Results and underlying data from this trial will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03865160.

Comparison of Safety of RADial comPRESSion Devices: A Multi-Center Trial of Patent Hemostasis following Percutaneous Coronary Intervention from Conventional Radial Access (RAD-PRESS Trial).

Although radial access is the current gold standard for the implementation of percutaneous coronary interventions (PCI), post-procedural radial compression devices are seldom compared with each other in terms of safety or efficacy. Our group aimed to compare a cost effective and potentially green method to dedicated radial compression devices, with respect to access site complications combined in a device oriented complex endpoint (DOCE), freedom from which served as our primary endpoint. Patients undergoing PCI were randomized to receive either the cost effective or a dedicated device, either of which were removed using patent hemostasis. Twenty-four hours after the procedure, radial artery ultrasonography was performed to evaluate the access site. The primary endpoint was assessed using a non-inferiority framework with a non-inferiority margin of five percentage points, which was considered as the least clinically meaningful difference. The cost-effective technique and the dedicated devices were associated with a comparably low rate of complications (freedom from DOCE: 83.3% vs. 70.8%, absolute risk difference: 12.5%, one-sided 95% confidence interval (CI): 1.11%). Composition of the DOCE (i.e., no complication, hematoma, pseudoaneurysm, and radial artery occlusion) and compression time were also assessed in superiority tests as secondary endpoints. Both the cost-effective technique and the dedicated devices were associated with comparably low rates of complications: p = 0.1289. All radial compression devices performed similarly when considering the time to complete removal of the respective device (120.0 (inter-quartile range: 100.0-142.5) for the vial vs. 120.0 (inter-quartile range: 110.0-180) for the dedicated device arm, with a median difference of [95% CI]: 7.0 [-23.11 to 2.00] min, p = 0.2816). In conclusion, our cost-effective method was found to be non-inferior to the dedicated devices with respect to safety, therefore it is a safe alternative to dedicated radial compression devices, as well as seeming to be similarly effective.

Ranibizumab in retinopathy of prematurity - one-year follow-up of ophthalmic outcomes and two-year follow-up of neurodevelopmental outcomes from the CARE-ROP study.

PURPOSE: The primary endpoint results from the comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity (CARE-ROP) core study identified ranibizumab as an effective treatment to control acute retinopathy of prematurity (ROP). This study reports the 1- and 2-year follow-up data focusing on long-term functional outcomes and safety. METHODS: The CARE-ROP trial compared 0.12 mg versus 0.20 mg ranibizumab in 20 infants with ROP in a multicentric, prospective, randomized, double-blind, controlled study design. Sixteen patients entered the follow-up period. An ophthalmologic assessment at one year postbaseline was acquired from all 16 patients and a neurodevelopmental assessment at two years postbaseline was acquired from 15 patients. RESULTS: Fifteen of 16 infants were able to fixate and follow moving objects at one year postbaseline treatment. One child progressed to stage 5 ROP bilaterally between the end of the core study and the 1-year follow-up (first seen at PMA 75 weeks). Mean spherical equivalents were -1.9 diopters (D) and -0.75 D in the 0.12 mg and the 0.20 mg treatment arms. Strabismus was present in seven and nystagmus in five out of 16 infants. Mental development scores were within normal limits in six out of ten patients with available data. No statistically significant difference was observed between the two treatment arms. CONCLUSION: Neurodevelopmental and functional ocular outcomes 1 and 2 years after treatment with ranibizumab are reassuring regarding long-term safety. Late reactivation of ROP, however, represents a challenge during the follow-up phase and it is of utmost importance that regular follow-ups are maintained.

Who has the worst attitudes toward sexual minorities? Comparison of transphobia and homophobia levels in gender dysphoric individuals, the general population and health care providers.

PURPOSE: To date, few studies have addressed attitudes toward transgender individuals. In addition, little is known about health care providers' (HCP) attitudes toward sexual minorities. The aim of the present study is to compare attitudes toward homosexual and transgender individuals between gender dysphoric individuals (GDs), general population controls (C) and HCP. METHODS: A total of 310 subjects were considered, including 122 GDs (63 transwomen and 59 transmen), 53 heterosexual HCP (26 males and 27 females) and 135 C. Participants completed the Modern Homophobia Scale (MHS) and the Attitudes Toward Transgendered Individuals Scale (ATTI) in order to assess attitudes toward gay men and lesbian women and toward transgender individuals, respectively. In addition, GDs completed the Gender Identity/Gender Dysphoria Questionnaire (GIDYQ-AA) and ATTI to measure, respectively, gender dysphoria levels and internalized transphobia. Religious attitudes were evaluated by means of the Religious Fundamentalism Scale (RFS), and Discrimination and Stigma Scale (DISC-12) was used to measure perceived discrimination. RESULTS: (1) Men showed significantly higher levels of homophobia and transphobia when compared to women (p < 0.001); (2) perceived discrimination was higher in lesbian women compared to gay men and in transwomen compared to transmen (p < 0.001 and p < 0.05, respectively); and (3) religious fundamentalism was associated with both homophobia and transphobia (both p < 0.001). CONCLUSIONS: Our results underline the need to promote awareness and acceptance of the sexual minorities, who are more at risk of discriminatory attitudes, which are strongly dependent on religious precepts and dogma.

Which are the male factors associated with female sexual dysfunction (FSD)?

It has been generally assumed that partner's erectile dysfunction, premature, and delayed ejaculation play a significant role in determining female sexual dysfunction (FSD). This study aimed to evaluate the role of the male partner's sexual function, as perceived by women, in determining FSD. A consecutive series of 156 heterosexual women consulting our clinic for FSD was retrospectively studied. All patients underwent a structured interview and completed the Female Sexual Function Index (FSFI). FSFI total score decreased as a function of partner's age, conflicts within the couple, relationship without cohabitation and the habit of engaging in intercourse to please the partner; FSFI total score increased as a function of frequency of intercourse, attempts to conceive and fertility-focused intercourse. FSFI total score showed a negative, stepwise correlation with partner's perceived hypoactive sexual desire (HSD) (r = -0.327; p < 0.0001), whereas no significant correlation was found between FSFI and erectile dysfunction, premature and delayed ejaculation. In an age-adjusted model, partner's HSD was negatively related to FSFI total score (Wald = 9.196, p = 0.002), arousal (Wald = 7.893, p = 0.005), lubrication (Wald = 5.042, p = 0.025), orgasm (Wald = 9.293, p = 0.002), satisfaction (Wald = 12.764, p < 0.0001), and pain (Wald = 6.492, p = 0.011) domains. Partner's HSD was also significantly associated with somatized anxiety, low frequency of intercourse, low partner's care for the patient's sexual pleasure, and with a higher frequency of masturbation, even after adjusting for age. In patients not reporting any reduction in libido, FSFI total score was significantly lower when their partner's libido was low (p = 0.041); the correlation disappeared if the patient also experienced HSD. In conclusion, the presence of erectile dysfunction, premature, and delayed ejaculation of the partner may not act as a primary contributing factor to FSD, as determined by FSFI scores; conversely, women's sexuality seems to be mostly impaired by the perceived reduction in their partner's sexual interest.

Gender identity, gender assignment and reassignment in individuals with disorders of sex development: a major of dilemma.

INTRODUCTION: Disorders of Sex Development (DSD) are a wide range of congenital conditions characterized by an incongruence of components involved in sexual differentiation, including gender psychosexual development. The management of such disorders is complex, and one of the most crucial decision is represented by gender assignment. In fact, the primary goal in DSD is to have a gender assignment consistent with the underlying gender identity in order to prevent the distress related to a forthcoming Gender Dysphoria. Historically, gender assignment was based essentially on surgical outcomes, assuming the neutrality of gender identity at birth. This policy has been challenged in the past decade refocusing on the importance of prenatal and postnatal hormonal and genetic influences on psychosexual development. AIMS: (1) to update the main psychological and medical issues that surround DSD, in particular regarding gender identity and gender assignment; (2) to report specific clinical recommendations according to the different diagnosis. METHODS: A systematic search of published evidence was performed using Medline (from 1972 to March 2016). Review of the relevant literature and recommendations was based on authors' expertise. RESULTS: A review of gender identity and assignment in DSD is provided as well as clinical recommendations for the management of individuals with DSD. CONCLUSIONS: Given the complexity of this management, DSD individuals and their families need to be supported by a specialized multidisciplinary team, which has been universally recognized as the best practice for intersexual conditions. In case of juvenile GD in DSD, the prescription of gonadotropin-releasing hormone analogues, following the World Professional Association for Transgender Health and the Endocrine Society guidelines, should be considered. It should always be taken into account that every DSD person is unique and has to be treated with individualized care. In this perspective, international registries are crucial to improve the understanding of these challenging conditions and clinical practice, in providing a better prediction of gender identity.

Bringing the body of the iceberg to the surface: the Female Sexual Dysfunction Index-6 (FSDI-6) in the screening of female sexual dysfunction.

PURPOSE: Female Sexual Dysfunction (FSD) is a still poorly studied and underdiagnosed condition. The aim of the study was to produce an improved version of FSFI-6 (6-Item Version of the Female Sexual Function Index), entitled Female Sexual Dysfunction Index-6 (FSDI-6), and to estimate its accuracy as a screening instrument for FSD. METHODS: In the new version, an item related to the personal interest in having a satisfying sex life was added, while the item rating the entity of sexual arousal was removed. We administered FSDI-6 in a consecutive series of female adult patients not consulting for sexual problems (n = 120, Cohort 1), and in another series of patients specifically consulting for sexual problems, which were considered as the control group (n = 160, Cohort 2). RESULTS: FSDI-6 score was significantly higher in patients in Cohort 2 (p < 0.0001). Cronbach's alpha for FSDI-6 was 0.784, indicating a high level of reliability. The estimated area under the ROC curve for FSDI-6 was 0.657 (p < 0.0001, 95 % CI 0.584-0.730). The proportion of subjects with a pathological FSDI-6 score (≥16.5) was 29.9 (n = 32) and 59.4 % (n = 95) in Cohort 1 and 2, respectively (p < 0.0001). Among subjects with a pathological FSDI-6 (score ≥16.5), those consulting for FSD had been postmenopausal for fewer years, had a higher level of education, a lower BMI and a lower prevalence of chronic diseases than those not consulting for FSD (p < 0.05). CONCLUSIONS: Although a lower educational level, overweight/obesity, menopause and chronic diseases are risk factors for FSD, they are often associated with the failure in medical consultation for FSD. We propose that FSDI-6 should be performed by health care providers in non-specialist settings to detect potential FSD, which otherwise could remain under-diagnosed.

Childhood maltreatment in subjects with male-to-female gender identity disorder.

Childhood maltreatment (CM) is quite common and constitutes a nonspecific risk factor for a range of different psychiatric symptoms during lifespan. It has been demonstrated that sexual minorities are at higher risk of maltreatment and abuse, and a high proportion of transsexual subjects report CM. The aim of this study is to evaluate the prevalence of reported CM in a clinical sample of patients with male-to-female Gender Identity Disorder (MtF GID), and to explore the relationship between these early life events, body image and different psychopathological and clinical variables. A consecutive series of 162 patients with male genotype was evaluated from July 2008 to May 2010. A total of 109 subjects (mean age 36 ± 10 years) meeting the criteria for MtF GID and giving their informed consent were considered. The occurrence of CM experiences was evaluated through a face-to-face clinical interview. Patients were asked to complete the Body Uneasiness Test and Symptom Checklist-90 Revised. More than one-fourth of patients reported CM. Maltreated subjects reported a higher body dissatisfaction and display a worse lifetime mental health. The presence of reported CM in these patients has relevant psychopathological implications, and therefore should be carefully investigated.

Intrasession variability of the full-field ERG.

OBJECTIVES: (1) To document variability of the full-field ERG within single recording sessions under ISCEV standards. (2) To identify clinical factors contributing to the observed variability. METHODS: Nine volunteer subjects were studied, aged 19-32 with no history of retinal disease. ISCEV standard ERGs were recorded. Dark-adapted "standard combined" and light-adapted "cone" b-wave amplitudes and implicit times were measured. Multiple flashes were presented at different interflash intervals and after different periods of dark and light adaptation. The stability of the stimulus flash was measured with a photometer. RESULTS: The statistical coefficient of variability was roughly 2.5% for the standard combined b-wave amplitude and 4.5% for the cone b-wave. B-wave implicit times showed a coefficient of variability of 2% for standard combined responses and 1.25% for cone responses. Variation in interflash interval, dark and light adaptation times, and sporadic unusual waveforms influenced measured b-wave amplitudes. CONCLUSION: Intrasession variability is much lower than previously reported values for intersession variability. Nonetheless, it represents a baseline of variability that will affect results and that may be minimized by recognition and control of contributing factors.

Gene transfer to rabbit retina with electron avalanche transfection.

PURPOSE: Nonviral gene therapy represents a promising treatment for retinal diseases, given clinically acceptable methods for efficient gene transfer. Electroporation is widely used for transfection, but causes significant collateral damage and a high rate of cell death, especially in applications in situ. This study was conducted in the interest of developing efficient and less toxic forms of gene transfer for the eye. METHODS: A novel method for nonviral DNA transfer, called electron avalanche transfection, was used that involves microsecond electric plasma-mediated discharges applied via microelectrode array. This transfection method, which produces synchronized pulses of mechanical stress and high electric field, was first applied to chorioallantoic membrane as a model system and then to rabbit RPE in vivo. Gene transfer was measured by using luciferase bioluminescence and in vivo fluorescent fundus photography. Safety was evaluated by performing electroretinograms and histology. RESULTS: In chorioallantoic membrane, electron avalanche transfection was approximately 10,000-fold more efficient and produced less tissue damage than conventional electroporation. Also demonstrated was efficient plasmid DNA transfer to the rabbit retina after subretinal DNA injection and transscleral electron avalanche transfection. Electroretinograms and histology showed no evidence of damage from the procedure. CONCLUSIONS: Electron avalanche transfection is a powerful new technology for safe DNA delivery that has great promise as a nonviral system of gene transfer.