The relationship between adverse interpersonal experiences and self-esteem in people with intellectual disabilities: The role of shame, self-compassion and social support.

BACKGROUND: People with intellectual disabilities are reported to have low self-esteem and to experience high rates of adverse interpersonal experiences (AIEs). This study aimed to investigate whether shame and self-compassion mediate the relationship between AIEs and self-esteem for people with intellectual disabilities and whether perceived social support moderates this relationship. METHOD: This study employed a cross-sectional design, involving between-group comparisons. Forty-seven people with intellectual disabilities and 50 people without intellectual disabilities completed self-report questionnaires measuring shame, self-compassion, self-esteem, early AIEs and social support. RESULTS: Shame and self-compassion were found to mediate the relationship between AIEs and self-esteem for people with intellectual disabilities. There was no evidence for a moderating effect of social support and no difference between groups in shame or self-compassion. CONCLUSIONS: The findings suggest shame and self-compassion are important concepts for people with intellectual disabilities. Clinical and research implications are discussed.

Panel-Based Clinical Genetic Testing in 85 Children with Inherited Retinal Disease.

PURPOSE: To assess the clinical usefulness of genetic testing in a pediatric population with inherited retinal disease (IRD). DESIGN: Single-center retrospective case series. PARTICIPANTS: Eighty-five unrelated children with a diagnosis of isolated or syndromic IRD who were referred for clinical genetic testing between January 2014 and July 2016. METHODS: Participants underwent a detailed ophthalmic examination, accompanied by electrodiagnostic testing (EDT) and dysmorphologic assessment where appropriate. Ocular and extraocular features were recorded using Human Phenotype Ontology terms. Subsequently, multigene panel testing (105 or 177 IRD-associated genes) was performed in an accredited diagnostic laboratory, followed by clinical variant interpretation. MAIN OUTCOME MEASURES: Diagnostic yield and clinical usefulness of genetic testing. RESULTS: Overall, 78.8% of patients (n = 67) received a probable molecular diagnosis; 7.5% (n = 5) of these had autosomal dominant disease, 25.4% (n = 17) had X-linked disease, and 67.2% (n = 45) had autosomal recessive disease. In a further 5.9% of patients (n = 5), a single heterozygous ABCA4 variant was identified; all these participants had a spectrum of clinical features consistent with ABCA4 retinopathy. Most participants (84.7%; n = 72) had undergone EDT and 81.9% (n = 59) of these patients received a probable molecular diagnosis. The genes most frequently mutated in the present cohort were CACNA1F and ABCA4, accounting for 14.9% (n = 10) and 11.9% (n = 8) of diagnoses respectively. Notably, in many cases, genetic testing helped to distinguish stationary from progressive IRD subtypes and to establish a precise diagnosis in a timely fashion. CONCLUSIONS: Multigene panel testing pointed to a molecular diagnosis in 84.7% of children with IRD. The diagnostic yield in the study population was significantly higher compared with that in previously reported unselected IRD cohorts. Approaches similar to the one described herein are expected to become a standard component of care in pediatric ophthalmology. We propose the introduction of genetic testing early in the diagnostic pathway in children with clinical and/or electrophysiologic findings, suggestive of IRD.

High dose cefuroxime causing retinal toxicity in a patient undergoing trabeculectomy.

PURPOSE: To present a case of severe retinal toxicity secondary to high dose intracameral cefuroxime administered during trabeculectomy glaucoma surgery. We describe the clinical features and management, and describe serial multimodal imaging and electrophysiological findings. Intracameral cefuroxime (ICC) and subconjunctival cefuroxime (SCC) are routinely administered during ocular surgeries to prevent postoperative endophthalmitis. Cefuroxime toxicity with both standard (1mg/0.1mL) and high doses of ICC (2-100mg) and SCC (31.25mg) have been reported. To the best of our knowledge, this is the first report of cefuroxime retinal toxicity in trabeculectomy surgery, which is of particular significance because of the possible differences in pharmacokinetics within the eye. OBSERVATIONS: A 69-year-old male with primary open-angle glaucoma, underwent right trabeculectomy, augmented with mitomycin C (0.2mg/mL). The patient inadvertently received cefuroxime 12.5mg/0.1mL as an intracameral rather than a subconjunctival injection. Within 4 hours, the error was discovered and the patient underwent immediate anterior chamber (AC) washout. His right best-corrected visual acuity was hand movements, and he rapidly developed uveitis including AC cells and moderate vitritis and haze. Optical coherence tomography (OCT) demonstrated serous macular detachment, characteristic schisis-like changes in the outer nuclear layer and ellipsoid zone disruption. Multi-focal electroretinograms (ERG) identified deficits undetected by full-field ERG. He was successfully managed with intensive local topical corticosteroid, non-steroidal therapy and peri-ocular corticosteroid injection. CONCLUSIONS AND IMPORTANCE: As ICC and SCC are routinely used in intra-ocular surgery to prevent endophthalmitis, ophthalmologists need to be aware of this potential complication and consider this in patients with unexplained reduced vision post-operatively. Theatre teams need to be vigilant about potential dilution and administration errors to ensure that the correct concentration and volume of cefuroxime is given via the correct route. We highlight the risks of high dose intracameral injection, including uveitis and retinal toxicity, and the utility of serial OCT, and full-field and multi-focal ERGs in this condition. We report a favourable outcome with significant and rapid improvement in retinal structure and function observed during follow-up. A literature review of the condition is presented.

Constitutive cyclo-oxygenase-2 does not contribute to the development of human visceral pain hypersensitivity.

BACKGROUND AND AIMS: Central sensitisation (CS), contributes to the development and maintenance of gastrointestinal pain hypersensitivity. Constitutive cyclo-oxygenase-2 (COX-2) contributes to central sensitisation in somatic pain hypersensitivity but its role in mediating visceral pain hypersensitivity is unknown. We therefore conducted a study to determine if COX-2 inhibition with Valdecoxib attenuates the development or early maintenance of CS in a validated human oesophageal pain hypersensitivity model. METHODS: Healthy volunteers were studied in two randomised, double blind, crossover studies in which pain thresholds (PT) to electrical stimulation were assessed in the proximal oesophagus, chest wall and foot, prior to and following a distal oesophageal acid infusion. Protocol 1: Valdecoxib, (40 mg) or matching placebo was given orally for 4 days prior to oesophageal acid infusion. Protocol 2: IV Parecoxib (40 mg) or saline was given 120 min after oesophageal acid infusion. RESULTS: Valdecoxib did not prevent the induction of secondary allodynia in the proximal oesophagus nor did it attenuate it following its establishment. Chest wall PT fell following oesophageal acid but foot PT remained unchanged; highlighting the development viscero-somatic convergence due to CS. Valdecoxib had no analgesic or anti-hyperalgesic effect on chest wall or foot PT. CONCLUSIONS: Neither the induction nor initial maintenance of acid induced oesophageal pain hypersensitivity is prevented by Valdecoxib, suggesting that constitutive spinal COX-2 does not contribute to the development or early maintenance of acute visceral central sensitisation.

Effects of the concentration and frequency of acid infusion on the development and maintenance of esophageal hyperalgesia in a human volunteer model.

Previous studies have demonstrated that a single 30-min distal esophageal infusion of concentrated (0.15 M, pH 0.8) hydrochloric acid (HCl) induces hyperalgesia to an electrical stimulus in a human model. The aim of this study was to refine this model using physiological acid concentrations (pH 1.8-4) in repeated short exposures. Two different cohorts of 10 volunteers underwent two studies. Study 1: randomization to four 5-min distal esophageal infusions of acid (0.15 M) or saline, 1 h apart. Double-blind measurements of baseline and postexposure proximal esophageal and chest wall pain thresholds (PTs) were performed to electrical stimulation at 30-min intervals throughout the study. Study 2: randomization to four 15-min infusions of 0.15, 0.075, and 0.01 M HCl and saline. In study 1, with multiple acid infusions, a significant progressive drop in PTs was observed in both areas tested (P < or = 0.0001). In study 2, increasing acid concentrations had a significant effect over multiple time points, P < or = 0.0001. Similar initial reductions in PTs were observed for all acid concentrations compared with saline; however, hypersensitivity was shorter lasting with 0.01 M acid. In healthy subjects, esophageal hypersensitivity can be induced and maintained up to 4 h by repeated short-duration acid infusion and at physiological pH levels. This has implications for future model design and pathophysiological understanding of acid-related esophageal hypersensitivity.

The development and maintenance of human visceral pain hypersensitivity is dependent on the N-methyl-D-aspartate receptor.

BACKGROUND & AIMS: Visceral hypersensitivity is a common feature of functional gastrointestinal disorders. One speculated mechanism is an activity-dependent increase in spinal cord neuronal excitability (central sensitization), which is dependent on activation of the N-methyl-D-aspartate (NMDA) receptor. Our aims were to determine whether the development and maintenance of human visceral hypersensitivity is NMDA receptor mediated. METHODS: Healthy subjects were studied using a randomized, double-blind, placebo-controlled, crossover design. Pain thresholds to electrical stimulation were determined both in the proximal esophagus and in the foot (control) before and after a 30-minute distal esophageal infusion of 0.15 mol/L HCl acid. Ketamine (NMDA receptor antagonist) or saline (vehicle) was given intravenously either prior to or following acid infusion, and pain thresholds were measured for the following 120 minutes. Protocol 1: In 6 subjects, the effect of ketamine in the esophagus was assessed without acid infusion. Protocol 2: In 14 subjects, ketamine was given prior to esophageal acid. Protocol 3: In 12 subjects, ketamine was given after esophageal acid. RESULTS: Protocol 1: In the absence of esophageal acid, ketamine had no effect on either esophageal or foot pain thresholds (area-under-the-curve, [AUC] P = 0.36 esophagus, P = 0.34 foot, ANOVA) within 30 minutes of cessation of the infusion. Protocol 2: Acid-induced esophageal hypersensitivity was prevented by ketamine (AUC, P < 0.0001, ANOVA) without affecting foot pain thresholds (AUC, P = 0.06, ANOVA). Protocol 3: Ketamine delivered after acid reversed the induction of esophageal hypersensitivity induced by acid (AUC, P < 0.0001, ANOVA). CONCLUSIONS: The induction and maintenance of acid-induced esophageal hypersensitivity is prevented and reversed by ketamine. This finding strongly indicates that central sensitization is a mechanism of visceral hypersensitivity.