A meta-analysis of the prevalence of attention deficit hyperactivity disorder in incarcerated populations.

BACKGROUND: Studies report the variable prevalence of attention deficit hyperactivity disorder (ADHD) in incarcerated populations. The aim of this meta-analysis was to determine the prevalence of ADHD in these populations. METHOD: Primary research studies reporting the prevalence (lifetime/current) of ADHD in incarcerated populations were identified. The meta-analysis used a mixed log-binomial model, including fixed effects for each covariate and a random study effect, to estimate the significance of various risk factors. RESULTS: Forty-two studies were included in the analysis. ADHD prevalence was higher with screening diagnoses versus diagnostic interview (and with retrospective youth diagnoses versus current diagnoses). Using diagnostic interview data, the estimated prevalence was 25.5% and there were no significant differences for gender and age. Significant country differences were noted. CONCLUSIONS: Compared with published general population prevalence, there is a fivefold increase in prevalence of ADHD in youth prison populations (30.1%) and a 10-fold increase in adult prison populations (26.2%).

Co-morbid psychiatric disorders among incarcerated ADHD populations: a meta-analysis.

BACKGROUND: Rates of psychiatric disorders are highly prevalent among prison inmates, and recent evidence confirms over-representation of youths and adults with attention deficit hyperactivity disorder (ADHD). The risk for psychiatric co-morbidity may be greater among offenders with ADHD. We undertook a systematic review and meta-analysis of reported rates of co-existing psychiatric morbidity with ADHD in prison samples. METHOD: Studies published from 1980 to 2015 were identified using five bibliographic indexes, review articles and reference lists. Included studies had a defined ADHD group and provided additional prevalence on at least one of the following: conduct disorder, substance use disorder, mood disorder, anxiety disorder, or personality disorder. We performed meta-analytical estimates of the prevalence of each co-morbid disorder within ADHD, and estimated the risk for co-existing disorders among prisoners with ADHD by pooling odds ratios (OR) with 95% confidence intervals. RESULTS: Eighteen studies with data for 1615 with ADHD and 3128 without ADHD were included. The risk (OR) of all psychiatric morbidity is increased among adult inmates with ADHD. Associations in youths with ADHD were restricted to mood disorder (OR 1.89, 95% confidence interval 1.09-3.28). CONCLUSIONS: This study quantifies the extent of co-morbidity presented by offenders with ADHD, especially adults. The differences between risk estimates for youths and adults indicate an incremental effect in both frequency and severity for the development of further co-morbid pathology through adulthood. The findings have implications for clinical intervention and for criminal justice policy.

Diverticular disease in Scotland: 2000-2010.

AIM: Symptomatic diverticular disease (DD) may be increasing in incidence in western society particularly in younger age groups. This study aimed to describe hospital admission rates and management for DD in Scotland between 2000 and 2010. METHOD: Data were obtained from the Scottish Morbidity Records (SMR01). The study cohort included all patients with a hospital admission and a primary diagnosis of DD of the large intestine (ICD-10 primary code K57). RESULTS: Scottish NHS hospitals reported 90 990 admissions for DD (in 87 314 patients) from 2000 to 2010. The annual number of admissions increased by 55.2% from 6591 in 2000 to 10,228 in 2010, an average annual increase per year of 4.5%. Most of the increase attributable to DD was due to elective day cases (3618 in 2000; 6925 in 2010) a likely consequence of a greater proportion of the population accessing colonoscopy over that time period. There was an 11% increase in inpatient admissions (2973-3303), 60% of these patients being women. Admissions in younger age groups increased proportionally in the later years of the study, and there was an association between DD admissions and greater deprivation. Despite an increase in complicated DD from 22.9% in 2000 to 27.1% in 2010 and a 16.8% increase in emergency inpatient admissions, the rate of surgery fell during the period of study. CONCLUSION: This report supports findings of other population-based studies of western countries indicating that DD is an increasing burden on health service resources, particularly in younger age groups.

Hereditary hyperferritinemia cataract syndrome: ocular, genetic, and biochemical findings.

PURPOSE: To describe the cataract morphology and genetic and biochemical findings in a four-generation family with hereditary hyperferritinemia cataract syndrome (HHCS). METHODS: Family members of the proband with HHCS were investigated. DNA sequencing was carried out to identify the iron responsive element (IRE) of the L-ferritin gene in affected and non-affected family members. Molecular modeling allowed prediction of the structure of the mutant IRE in affected cases. Serum ferritin and transferrin saturation were determined using standard methods. All family members underwent slit lamp examination by an ophthalmologist to document presence of cataract or lens status. Cataract morphology was documented where present. RESULTS: This family with HHCS had the genetic heterozygous mutation G32C in the IRE of the L-ferritin mRNA. Lens opacities were detectable in young members of the family, and morphology of cataracts was consistent with previous reports. Biochemical testing demonstrated high serum ferritin levels in affected individuals. CONCLUSIONS: The morphology of cataracts in HHCS seems to be similar in all cases. In the heterozygous G32C mutation, the age at onset of cataracts is very early. Greater awareness of this condition among ophthalmologists will lead to effective family counseling of those affected, by genetic testing or simple biochemical tests. Serum ferritin levels can be effectively used to screen for this condition in suspected families.

Pseudopterygium arising in a patient with multiple keloids.

We describe an unusual case of mechanical restriction of the globe caused by pseudopterygium formation at the site of a minor ocular injury, which led to a possible link between Ebstein's anomaly and keloids.

Long-Term Outcomes of ADHD: A Systematic Review of Self-Esteem and Social Function.

OBJECTIVE: To compare the long-term self-esteem and social function outcomes of individuals with untreated and treated ADHD across childhood, adolescence, and adulthood. METHOD: A systematic search of 12 databases was performed to identify peer-reviewed, primary research articles, published January 1980 to December 2011, reporting long-term self-esteem and/or social function outcomes (≥2 years; life consequences distinct from symptoms) of individuals with untreated or treated ADHD. RESULTS: Overall, 127 studies reported 150 outcomes. Most outcomes were poorer in individuals with untreated ADHD versus non-ADHD controls (57% [13/23] for self-esteem; 73% [52/71] for social function). A beneficial response to treatment (pharmacological, nonpharmacological, and multimodal treatments) was reported for the majority of self-esteem (89% [8/9]) and social function (77% [17/22]) outcomes. CONCLUSION: Untreated ADHD was associated with poorer long-term self-esteem and social function outcomes compared with non-ADHD controls. Treatment for ADHD was associated with improvement in outcomes; however, further long-term outcome studies are needed.

Predicted effect size of lisdexamfetamine treatment of attention deficit/hyperactivity disorder (ADHD) in European adults: Estimates based on indirect analysis using a systematic review and meta-regression analysis.

BACKGROUND: There are few approved therapies for adults with attention-deficit/hyperactivity disorder (ADHD) in Europe. Lisdexamfetamine (LDX) is an effective treatment for ADHD; however, no clinical trials examining the efficacy of LDX specifically in European adults have been conducted. Therefore, to estimate the efficacy of LDX in European adults we performed a meta-regression of existing clinical data. METHODS: A systematic review identified US- and Europe-based randomized efficacy trials of LDX, atomoxetine (ATX), or osmotic-release oral system methylphenidate (OROS-MPH) in children/adolescents and adults. A meta-regression model was then fitted to the published/calculated effect sizes (Cohen's d) using medication, geographical location, and age group as predictors. The LDX effect size in European adults was extrapolated from the fitted model. Sensitivity analyses performed included using adult-only studies and adding studies with placebo designs other than a standard pill-placebo design. RESULTS: Twenty-two of 2832 identified articles met inclusion criteria. The model-estimated effect size of LDX for European adults was 1.070 (95% confidence interval: 0.738, 1.401), larger than the 0.8 threshold for large effect sizes. The overall model fit was adequate (80%) and stable in the sensitivity analyses. CONCLUSION: This model predicts that LDX may have a large treatment effect size in European adults with ADHD.

Rejoining of gamma-radiation-induced single-strand breaks in plasmid DNA by human cell extracts: dependence on the concentration of the hydroxyl radical scavenger, Tris.

The rejoining of single-strand breaks induced by gamma irradiation in plasmid DNA under different scavenging conditions is described using human cell extracts. As the scavenging capacity of the irradiated solution increases from 1.5 x 10(7) to 3 x 10(8) s-1 using Tris-HCl as a scavenger, the ratio of single- to double-strand breaks is reduced from approximately 70:1 to 40:1. After irradiation, a proportion of DNA molecules have no initial strand breaks but contain damage that is converted to strand breaks when incubated either at 37 degrees C or in the presence of cellular extract. Repair of damage by the extracts is dependent upon the scavenging capacity of the irradiated solution. Optimal rejoining is observed when the scavenging capacity is < 1.5 x 10(7) s-1, and results in the repair of some initial strand breaks. As the scavenging capacity increases to 3 x 10(8) s-1 the proportion of breaks repaired is significantly reduced. The relative increase in the yield of double-strand breaks and reduced repairability of single-strand breaks at a scavenging capacity of 3 x 10(8) s-1 is consistent with the concept that the severity of damage increases upon increasing the scavenger concentration.

The severity of alpha-particle-induced DNA damage is revealed by exposure to cell-free extracts.

The rejoining of single-strand breaks induced by alpha-particle and gamma irradiation in plasmid DNA under two scavenging conditions has been compared. At the two scavenger capacities used of 1.5 x 10(7) and 3 x 10(6) s-1 using Tris-HCl as the scavenger, the ratio of single- to double-strand breaks for alpha particles is fivefold less than the corresponding ratios for gamma irradiation. The repair of such radiation-induced single-strand breaks has been examined using a cell-free system derived from human whole-cell extracts. We show that the rejoining of single-strand breaks for both alpha-particle- and gamma-irradiated plasmid is dependent upon the scavenging capacity and that the efficiency of rejoining of alpha-particle-induced single-strand breaks is significantly less than that observed for gamma-ray-induced breaks. In addition, for DNA that had been irradiated under conditions that mimic the cellular environment with respect to the radical scavenging capacity, 50% of alpha-particle-induced single-strand breaks are converted to double-strand breaks, in contrast with only approximately 12% conversion of gamma-ray-induced single-strand breaks, indicating that the initial damage caused by alpha particles is more severe. These studies provide experimental evidence for increased clustering of damage which may have important implications for the induction of cancer by low-level alpha-particle sources such as domestic radon.

Reduced transferrin binding in Down syndrome: a route to senile plaque formation and dementia.

Plasma transferrin binding in Down syndrome and Alzheimer's disease is significantly reduced compared with age matched controls and it was thought this may help elucidate a pathological time sequence for the onset of dementia in Down syndrome. In Down syndrome, there was a reduction in gallium and aluminium transferrin binding both with age and the onset of dementia. Non-transferrin bound gallium species were identified as non-transportable phosphate or silicate. Thus, the route of entry of metals into the brain must be via a transferrin mediated complex only. A clear sequence of pathological events has been demonstrated in Down syndrome which shows the pathway to development of plaques and dementia and this is believed to have an immunological origin.

Gallium-transferrin binding in treated and untreated Parkinson's disease.

The binding of gallium (Ga) to transferrin (Tf) was studied in plasma from control patients, in patients with untreated Parkinson's disease (PD) and in patients with PD treated either with levodopa (L-dopa) alone or in combination with selegiline. Mean percentage Ga-Tf binding was significantly reduced in untreated and treated PD compared with controls. Binding, however, was significantly greater in treated than in untreated patients. There was no difference in binding between patients treated with L-dopa alone and those treated with L-dopa and selegiline. The data support the hypothesis that oxidation reactions may be of pathogenic significance in PD.

Subcutaneous tissue approximation in relation to wound disruption after cesarean delivery in obese women.

OBJECTIVE: To test the hypothesis that closure of the subcutaneous fat decreases the incidence of wound disruption after cesarean delivery. METHODS: Two hundred forty-five women with at least 2 cm of subcutaneous fat were randomized to closure of the Camper fascia or no closure with cesarean delivery. RESULTS: Complications leading to disruption or opening of the incision were classified as wound seromas in 28 women (11.4%) and as wound infections in 17 (7.0%). The relative risk (RR) of seroma formation in the subcutaneous closure group was 0.3 with a 95% confidence interval (CI) of 0.1-0.7 (5.1 versus 17.2%), a statistically significant difference. There was no significant difference in the incidence of wound infections in the two study groups. Overall, there was a significant difference in the incidence of wound disruption from all causes between the two groups: 14.5% in the subcutaneous closure group compared with 26.6% when the subcutaneous tissues were not reapproximated (RR 0.5, 95% CI = 0.3-0.9). CONCLUSION: Closure of the subcutaneous tissue can significantly reduce the rate of postoperative wound disruption in women with at least 2 cm of subcutaneous adipose tissue.

Indole-3-propionate: a potent hydroxyl radical scavenger in rat brain.

The hydroxyl radical scavenging activity of indole-3-propionate was evaluated by kinetic competition studies with the hydroxyl radical trapping reagent 2,2'-azino-bis-(3-ethyl-benz-thiazoline-6-sulfonic acid) (ABTS) and by measuring hydroxyl radical-initiated lipid peroxidation in the rat striatum. Using ABTS, the indole was shown to act as a potent hydroxyl radical scavenger with a rate constant of 7.8x1010 mol l-1 s-1. Hydroxyl radical-initiated lipid peroxidation, determined by measuring tissue malondialdehyde formation, was inhibited dose-dependently both in vitro and in vivo. Indole-3-propionate reacts with hydroxyl radicals at a diffusion controlled rate and can thereby provide on-site protection against the oxidative damage of biomolecules induced by these highly reactive and toxic oxygen intermediates. While it remains to be established if endogenous brain tissue levels of indole-3-propionate are sufficiently high to have a significant impact on total antioxidative capacity, the compound itself or a structurally related agent may be useful as an antioxidant adjuvant to combat hydroxyl radical-mediated oxidative stress.

Quantitative differences in the effects of de novo produced and exogenous kynurenic acid in rat brain slices.

Kynurenic acid (KYNA) is an antagonist of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors and it blocks the glycine site of the NMDA receptor preferentially (IC50 = 7.9 microM). KYNA is produced endogenously by transamination of its precursor L-kynurenine (L-KYN). We tested the hypothesis that effects of endogenous, de novo produced KYNA, following bath-application of L-KYN to slices, would be different than effects of commercially-synthesized (exogenous) KYNA. The ability to block spontaneous epileptiform activity, induced by lowering extracellular magnesium, was examined in area CA3 of hippocampus and the entorhinal cortex. At a concentration of 200 microM L-KYN, which produced 0.89 +/- 0.20 microM KYNA, there were fewer slices with spontaneous epileptiform activity than slices exposed to 2 microM exogenous KYNA. The results indicate a more potent neuromodulatory action of endogenous KYNA than has been previously realized.

The nanophthalmic macula.

AIMS: To define an unusual macular appearance found in association with nanophthalmos. METHODS: A case review. RESULTS: Seven children (aged 8 months to 17 years) with nanophthalmos were examined. They all exhibited the same clinical findings of an unusual yellow macula appearance with retinal folds and crowded optic discs. Visual electrophysiology performed in four cases was normal. CONCLUSION: A distinctive yellow macular pigmentation with associated chorioretinal folds and crowded optic discs is present in nanophthalmos. It is proposed that the retinal folds are due to a disparity between scleral and retinal growth while the macula discoloration is due to a congenital abnormality in arrangement or position of the luteal pigment and is not degenerative. Included in this case series is the second case in the literature of nanophthalmos associated with Kenny's syndrome. Inheritance of nanophthalmos appears to be autosomal recessive.

Neuroleptanalgesia and extracapsular cataract extraction.

Peribulbar and retrobulbar anaesthesia are commonly used techniques in cataract extraction. They offer satisfactory analgesia and akinesia but serious complications although uncommon are consistently reported. Intravenous sedation combined with a facial nerve block offers an alternative method of anaesthesia. This is a retrospective study of patients who underwent extracapsular cataract extraction using this technique between 1 January 1986 and 1 September 1990. The operating conditions were judged to be very suitable with minimal peroperative complications. The postoperative ocular complication rate was low (minimum follow-up 3 months) and no serious medical complications were noted: 93.8% of patients achieved 6/12 vision or better. This study demonstrates that it is possible to achieve satisfactory ocular analgesia and akinesia during cataract extraction under local anaesthesia without the use of a periocular injection.

Current practice of cataract extraction and anaesthesia.

A questionnaire regarding preferred methods of cataract extraction and anaesthesia was sent to 456 consultant ophthalmologists in England and Wales. Replies were received from 86% (n = 392), 83% (n = 380) having completed the questionnaire in full. The most frequently employed surgical approach was non-automated extracapsular cataract extraction. Only 2% of surgeons (n = 8) used phacoemulsification routinely and 2% (n = 7) used intracapsular extraction. Intraocular lens implantation was the standard practice of 99% of surgeons (n = 376). There has been a dramatic increase in the popularity of local anaesthesia, which was employed routinely (in more than three-quarters of their cases) by 20% of surgeons (n = 76). Retrobulbar infiltration remains the most common method of administration. Sedation was given routinely by 45% of surgeons (n = 171) when using local anaesthesia. Medical contraindications and patient preference were considered the most important reasons for selecting local anaesthesia rather than general. The exclusive use of general anaesthesia in cataract surgery appears to be diminishing.

The eye in epidermolysis bullosa.

AIMS: To describe the ophthalmic findings in a large cohort of epidermolysis bullosa (EB) patients managed in one large specialist centre. METHODS: A case note review of consecutive patients seen at Great Ormond Street Children's Hospital. Data on the dermatological disease, ophthalmic history, and examination were collected and coded onto a data sheet. RESULTS: 181 patients: 50 (28%) simplex EB; 15 (8%) junctional EB; 28 (15%) autosomal dominant dystrophic EB; 72 (40%) autosomal recessive dystrophic EB; nine patients (5%) with dystrophic EB whose inheritance could not be ascertained; and seven cases (4%) of EB that could not be classified. Ocular problems were found in 12% (n = 6) of simplex patients and 40% (n = 6) of those with junctional disease. One patient (of 28) in the autosomal dominant dystrophic group had ocular involvement and 51% (37/72) of patients in the autosomal recessive dystrophic group had ophthalmic complications: corneal (25/72), lid ectropions (3/72), lid blisters (5/72), and symblepharon (3/72). CONCLUSION: Ophthalmic complications are common in EB overall but the incidence varies widely with subtype. Ophthalmic complications are the most severe in the dystrophic recessive and junctional subtypes where there is a need for extra vigilance. The major treatment modality was use of ocular lubricants.

Optic disc anomalies and frontonasal dysplasia.

AIMS: To document the optic disc abnormalities in patients with frontonasal dysplasia in association with basal encephalocele. METHODS: Names and hospital numbers of patients with midline clefts were obtained from the ophthalmology and genetics database. Six patients were identified who had the following common findings: midline facial cleft with midline cleft lip and palate; hypertelorism; absent corpus callosum; basal (sphenoethmoidal) encephalocele; and pituitary deficiency (five out of six cases). Ophthalmic examination was performed with fundal photography where possible. RESULTS: Two patients had unilateral and one a bilateral peripapillary staphyloma. Two patients had bilateral optic disc hypoplasia and one appeared to have a peripapillary staphyloma in one eye and a morning glory disc in the other. CONCLUSION: Optic disc abnormalities were found in all patients with this constellation of clinical findings. This association appears to represent a distinct subgroup within the spectrum of frontonasal dysplasia. The presence of midline facial anomalies and any dysplastic disc should alert the physician as to the presence of an encephalocele.

Modulation and function of kynurenic acid in the immature rat brain.

Using in vivo and in vitro paradigms, the regulation and function of the brain metabolite kynurenic acid (KYNA) was examined in rats on postnatal days (PND) 7 and 14. As shown previously in adult rats, glucose removal and d-amphetamine (d-Amph) administration caused decreases in KYNA formation, while exposure to pyruvate up-regulated KYNA synthesis. The effect of glucose deprivation was substantially blunted in immature animals. In PND 14 rats, d-Amph pre-treatment exacerbated the excitotoxic effects of an intrastriatal N-methyl-D-aspartate (NMDA) injection. This potentiation was prevented by m-nitrobenzoylalanine, a kynurenine 3-hydroxylase inhibitor that also antagonized the KYNA reduction caused by d-Amph. These and additional experiments with the competitive NMDA receptor antagonist CGP 40116 indicate the existence of a functionally significant, novel high-affinity receptor for KYNA in the brain.