Health-related quality of life and burden of illness in adults with newly diagnosed attention-deficit/hyperactivity disorder in Sweden.

BACKGROUND: This observational, cross-sectional, retrospective chart review aimed to identify factors determining health-related quality of life (HRQoL) in adults with newly diagnosed attention-deficit/hyperactivity disorder (ADHD) in Sweden. METHODS: Adult participants with a new clinical diagnosis of ADHD were enrolled from two specialist outpatient clinics in Stockholm, Sweden, from 2013 to 2015. Data extracted from patient records included demographics, clinical characteristics and comorbid psychiatric diagnoses identified using the Mini International Neuropsychiatric Interview (MINI). Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale - Self-reported (MADRS-S). The self-rated five-dimension EuroQol questionnaire (EQ-5D) was used to measure HRQoL. Predictors of EQ-5D index score were identified using multivariate linear regression adjusting for age, sex, education level, and main income source. RESULTS: The mean age of the 189 enrolled patients was 35.2 years (standard deviation [SD], 12.3), and 107 (57%) were female. Psychiatric comorbidities were present in 92 patients (49%), with anxiety and depression being the most common diagnoses. The mean EQ-5D index score was 0.63 (SD, 0.28). Low EQ-5D index scores were significantly associated with high MADRS-S scores, multiple comorbid psychiatric disorders, low educational achievement, female sex, and not having a main income derived from employment or self-employment. CONCLUSIONS: These findings suggest that adults with newly diagnosed ADHD experience low HRQoL, which may often be exacerbated by psychiatric comorbidities such as anxiety and depression. Patients presenting with ADHD and psychiatric comorbidities in adulthood may require particular care and resources in the management of their ADHD.

Perinatal and long-term effects of maternal uterine artery adenoviral VEGF-A165 gene therapy in the growth-restricted guinea pig fetus.

Uterine artery application of adenoviral vascular endothelial growth factor A165 (Ad.VEGF-A165) gene therapy increases uterine blood flow and fetal growth in experimental animals with fetal growth restriction (FGR). Whether Ad.VEGF-A165 reduces lifelong cardiovascular disease risk imposed by FGR remains unknown. Here, pregnant guinea pigs fed 70% normal food intake to induce FGR received Ad.VEGF-A165 (1×1010 viral particles, n = 15) or vehicle ( n = 10), delivered to the external surface of the uterine arteries, in midpregnancy. Ad libitum-fed controls received vehicle only ( n = 14). Litter size, gestation length, and perinatal mortality were similar in control, untreated FGR, and FGR+Ad.VEGF-A165 animals. When compared with controls, birth weight was lower in male but higher in female pups following maternal nutrient restriction, whereas both male and female FGR+Ad.VEGF-A165 pups were heavier than untreated FGR pups ( P < 0.05, ANOVA). Postnatal weight gain was 10-20% greater in female FGR+Ad.VEGF-A165 than in untreated FGR pups, depending on age, although neither group differed from controls. Maternal nutrient restriction reduced heart weight in adult female offspring irrespective of Ad.VEGF-A165 treatment but did not alter ventricular wall thickness. In males, postnatal weight gain and heart morphology were not affected by maternal treatment. Neither systolic, diastolic, mean arterial pressure, adrenal weight, nor basal or challenged plasma cortisol were affected by maternal undernutrition or Ad.VEGF-A165 in either sex. Therefore, increased fetal growth conferred by maternal uterine artery Ad.VEGF-A165 is sustained postnatally in FGR female guinea pigs. In this study, we did not find evidence for an effect of maternal nutrient restriction or Ad.VEGF-A165 therapy on adult offspring blood pressure.

The use of ultrasound to assess fetal growth in a guinea pig model of fetal growth restriction.

Fetal growth restriction (FGR) is a common and potentially severe pregnancy complication. Currently there is no treatment available. The guinea pig is an attractive model of human pregnancy as placentation is morphologically very similar between the species. Nutrient restriction of the dam creates growth-restricted fetuses while leaving an intact uteroplacental circulation, vital for evaluating novel therapies for FGR. Growth-restricted fetuses were generated by feeding Dunkin Hartley guinea pig dams 70% of ad libitum intake from four weeks before and throughout pregnancy. The effect of maternal nutrient restriction (MNR) on dams and fetuses was carefully monitored, and ultrasound measurements of pups collected. There was no difference in maternal weight at conception, however by five weeks post conception MNR dams were significantly lighter ( P < 0.05). MNR resulted in significantly smaller pup size from 0.6-0.66 gestation. Ultrasound is a powerful non-invasive tool for assessing the effect of therapeutic interventions on fetal growth, allowing longitudinal measurement of fetuses. This model and method yield data applicable to the human condition without the need for animal sacrifice and will be useful in the translation of therapies for FGR into the clinic.

Long-term (1 year) safety and efficacy of methylphenidate modified-release long-acting formulation (MPH-LA) in adults with attention-deficit hyperactivity disorder: a 26-week, flexible-dose, open-label extension to a 40-week, double-blind, randomised, placebo-controlled core study.

INTRODUCTION: Previously, in a 40-week, randomised, double-blind, placebo-controlled core study comprising three phases (9-week dose confirmation, 5-week open-label dose optimisation and 6-month maintenance of effect) in adults with attention-deficit/hyperactivity disorder (ADHD), methylphenidate modified-release long-acting formulation (MPH-LA) at 40-80 mg/day controlled ADHD symptoms as well as decreased functional impairment with a good tolerability profile (NCT01259492). Here, we report the long-term efficacy and safety from a 26-week, open-label extension phase of the same study (NCT01338818). METHODS: Patients in the extension study (n = 298) initiated treatment with MPH-LA (20 mg/day), up-titrated in increments of 20 mg/week to reach individual patient's daily optimal dose of 40-80 mg. Adverse events (AEs) and serious adverse events (SAEs) were reported at the end of extension study for events monitored from (1) maintenance of effect phase baseline (core study; 12 months) and (2) extension study baseline (6 months). Mean changes in DSM-IV ADHD Rating Scale (DSM-IV ADHD RS) and Sheehan Disability Scale (SDS) total scores are reported for both the timelines. Efficacy was also evaluated using clinician-rated instruments, namely Clinical Global Impression-Improvement Scale (CGI-I) and Clinical Global Impression-Severity Scale (CGI-S). RESULTS: No unexpected AEs were reported in the extension study. Incidence of SAEs reported during 6 months and 12 months were similar (0.7 %), and no deaths were reported. No SAEs were considered attributable to the drug at the end of 12 months. There were no reports of patients with QT, QTcB or QTcF >500 ms. The mean improvement in DSM-IV ADHD RS and SDS total scores at the end of 12 months were 0.9 and 1.4 points, respectively; and at the end of 6 months were 7.2 and 4.8, respectively. The proportion of patients with improvement in CGI-S scale was 31.4 % and 52.1 % at the end of 12 and 6 months, respectively. Overall, 69.4 % of patients showed clinical improvement in CGI-I scale at the end of 6 months. CONCLUSIONS: In adult patients with ADHD, use of MPH-LA up to 1 year continued to be well tolerated while maintaining the clinical efficacy.

Maternal lipopolysaccharide alters the newborn oxidative stress and C-reactive protein levels in response to an inflammatory stress.

Maternal infection is associated with oxidative stress (OS) and inflammatory responses. We have previously shown that maternal exposure to lipopolysaccharide (LPS) at E18 alters the subsequent offspring immune response. As immune responses are mediated, in part, by OS, we sought to determine if maternal inflammation during pregnancy programs offspring OS and C-reactive protein (CRP) levels. Pregnant Sprague-Dawley rats received intraperitoneal (i.p.) injections of saline or LPS at 18 days' gestation (n = 4), and pups delivered spontaneously at term. At postnatal day 24, male and female offspring received i.p. injection of LPS. Serum lipid peroxides formation (PD) and CRP levels were determined before and at 4 h following the LPS injection. Pups of LPS-exposed dams had significantly higher basal OS (PD 29.4 ± 5.4 v. 10.1 ± 4.8 nmol/ml) compared with controls. In response to LPS, CRP levels (20.4 ± 2.8 v. 5.7 ± 1.0 ng/ml) were significantly higher among pups of LPS-exposed dams than controls. Prenatal maternal exposure to LPS increases baseline OS levels in neonates and CRP levels in response to LPS. These results suggest that maternal inflammation during the antenatal period may induce long-term sequelae in the offspring that may predispose to adult disease.

Fear of crime among elderly Jews in Boston and London.

This article deals with the impact of fear of crime on the daily behavior of elderly Jews in two racially mixed, deteriorating neighborhoods, one in Boston and the other in London. Although people in both places expressed their fears in a similar language, their behavior was different: the Boston elderly retreated behind locked doors, while the London elderly continued their daily routine almost uninterrupted. Three factors are discussed: crime rate in each neighborhood, the different ecological pattern of both cities, and the impact of racial change. Above all, it seems, the different effect of fear of crime on behavior can be explained by the way the elderly regarded themselves vis-a-vis the community. The London Jews still felt themselves to be a part of their community while the Boston Jews felt alienated from it.