Multiple traumatisation and subsequent psychopathology in people with intellectual disabilities and DSM-5 PTSD: a preliminary study.

BACKGROUND: Individuals with intellectual disability (ID) are at greater risk of exposure to traumatic life events compared with the non-ID population. Yet no study to date has examined the role of multiple traumatisation and subsequent psychopathology in people with ID. The aim of this study was to explore the association between multiple traumatisation and subsequent mental health. METHODS: A preliminary cross-sectional study involving 33 participants with DSM-5 post-traumatic stress disorder completed self-report questionnaires on exposure to traumatic life events and post-traumatic stress disorder symptoms, anxiety, depression and general distress. RESULTS: A proportion of 42.4% of the sample reported multiple traumatisation, including exposure to life events in both childhood and adulthood. Those who reported exposure to life events in childhood and adulthood reported significantly higher risk of harm, depression and general psychological distress compared with those who reported exposure to life events only in adulthood. CONCLUSIONS: Preliminary results indicate that more severe psychopathology is associated with multiple traumatisation in childhood and adulthood compared with trauma experienced solely in adulthood.

Improving diabetes care for people with intellectual disabilities: a qualitative study exploring the perceptions and experiences of professionals in diabetes and intellectual disability services.

BACKGROUND: Globally, diabetes is increasing with concerns about the impact on outcomes, including premature death and the costs associated with managing the condition. Research indicates that adults with intellectual disabilities (ID) are two to three times more likely to develop diabetes; however, there has been limited focus on diabetes service utilisation in this population. The aim of this study is to explore the perceptions and experiences of diabetes and ID practitioners. METHODS: A series of 1:1 semi-structured interviews were undertaken in one Scottish health service area. In total, 29 qualitative interviews were conducted: 10 with diabetes practitioners from primary and secondary care, 14 from ID services and 5 from community care services regarding diabetes service provision for this population. Thematic content analysis was undertaken to identify the themes and subthemes. RESULTS: Three main themes were identified: (1) enabling access to services to meet diabetes-related care needs of people with ID; (2) communication and service improvements between staff, patients and across services; and (3) providing person-centred diabetes care and developing adapted resources to increase patient self-care. CONCLUSIONS: The findings of this study have important international implications in how diabetes practitioners plan and deliver services for people with ID and other vulnerable groups with limited cognitive ability and communication skills and difficulties in self-management. The findings highlight that access to diabetes education and adapted resources is needed, and if 'reasonable adjustments' are made to service provision and practice, people with ID can benefit from improved healthcare. Developing joint clinics to share knowledge and resources between diabetes and ID practitioners may improve service delivery and continuity of care, and thereby diminish the costs of not providing quality care.

First-in-human trial of the safety, pharmacokinetics and immunogenicity of a PEGylated anti-CD40L antibody fragment (CDP7657) in healthy individuals and patients with systemic lupus erythematosus.

OBJECTIVE: The objective of this paper is to investigate the safety, pharmacokinetics (PK) and immunogenicity of CDP7657, a PEGylated anti-CD40L antibody fragment, in healthy individuals and patients with systemic lupus erythematosus (SLE). METHODS: This randomized, double-blind, single-dose, dose-escalation phase I study consisted of two parts. In part 1, 28 healthy individuals received CDP7657 IV (0.004-5 mg/kg) or placebo. In part 2, 17 patients with SLE received CDP7657 IV (5-60 mg/kg) or placebo. The CDP7657:placebo ratio was 3:1. RESULTS: Adverse events (AEs) were reported by 76% of healthy individuals and 100% of patients with SLE treated with CDP7657; most were mild or moderate in intensity. Two healthy individuals reported serious AEs (SAEs), one of which was considered treatment related (infusion-related reaction; 5 mg/kg cohort). One patient with SLE (60 mg/kg cohort) experienced three SAEs, one of which was considered treatment related (herpes zoster infection). No thromboembolic events were reported. CPD7657 exposure increased in a dose-proportional manner. Low anti-CDP7657 antibody titres were detected in the majority of CDP7657-treated participants with no apparent impact on the PK of CDP7657. CONCLUSION: Single doses of CDP7657 showed predictable PK in healthy individuals and patients with SLE and were well tolerated, with no safety signals of concern. These findings support further investigation of CDP7657 as a therapy for SLE.

An investigation of executive function abilities in adults with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a genetic disorder caused by the absence of expression of maternally imprinted genes on the long arm of chromosome 15 (15q 11-13). There are two main genetic sub-types: (1) deletion, caused by the absence of paternally derived genetic material; and (2) uniparental disomy (UPD), where two copies of maternally derived chromosome 15 are present. In addition to generally mild/borderline intellectual disability (ID) and the almost universal feature of hyperphagia, PWS is associated with high rates of behaviour problems including temper tantrums, compulsive behaviour, perseverative speech, skin picking and rigid thinking. The present study seeks to explore whether these behaviours are associated with relative deficits in executive function (EF), which comprises the set of non-automatic processes utilized by an individual when faced with a novel situation. METHODS: Eighteen adult participants with a clinical diagnosis of PWS (12 with deletion sub-type, 6 with UPD) were recruited from a UK Health Service PWS clinic, and compared with 15 participants of similar age and verbal ability on a series of EF tasks and also Digit Span Forwards. An informant completed two ratings of behaviour, the Aberrant Behavior Checklist (ABC) and the Dysexecutive Questionnaire (DEX). RESULTS: The PWS group had significantly higher scores on the ABC but not on the DEX. There were no significant differences between the whole PWS group and the comparison group on any of the EF tasks. The deletion sub-type group was significantly poorer at a non-executive task, Digit Span Forwards. There was an unexpected trend for the deletion sub-type group to show more efficient performance on a visuospatial planning task, the Tower of London (TOL), but this trend did not reach significance. CONCLUSIONS: The lack of relative deficits in EF task performance does not support the hypothesis that EF differences could account for the high levels of behaviour problems found in PWS. Applying the Baddeley and Hitch model of working memory it is suggested that the PWS group have a relatively intact central executive and visuospatial sketchpad but a relative impairment in the phonological loop, perhaps relating to the capacity of the phonological store. This latter finding seems to be particularly salient for those with a deletion. As differences in EF ability were not found, it is suggested that a region of the brain involved in the modulation of emotion but not particularly with EF, the orbitofrontal cortex (OFC), may be implicated in the behaviour problems reported in PWS.

A double-blind placebo controlled randomised trial of misoprostol and oxytocin in the management of the third stage of labour.

OBJECTIVE: To compare oral misoprostol 400 microg with intramuscular oxytocin 10 IU in the routine management of the third stage. DESIGN: Double-blind placebo controlled trial. SETTING: Main referral hospital and its associated polyclinics in Accra, Ghana. POPULATION: Four hundred and one low risk women, in the second stage of labour with anticipated vaginal delivery, who entered labour spontaneously. METHODS: After delivery of the anterior shoulder of the baby, the women were randomised to receive either: 1. misoprostol 400 microg powder in water orally and 1 mL normal saline intramuscular injection (placebo); or 2. powdered cellulose in water orally (placebo) and 1 mL oxytocin 10 IU intramuscular injection. MAIN OUTCOME MEASURES: Change in haemoglobin concentration from before delivery to 12 hours postpartum. Secondary outcomes included need for additional oxytocics, blood loss > 500 mL and > 1,000 mL, operative intervention for postpartum haemorrhage, and side effects, including nausea, vomiting, diarrhoea, shivering and elevated temperature. RESULTS: Demographic characteristics were similar. There was no significant difference in change in haemoglobin concentration between the two groups (0.60 g/dL for misoprostol and 0.55 g/dL for oxytocin; relative difference 9.6%; 95% CI 20.5-39.6%; P = 0.54). There were no significant differences in secondary outcomes with the exception of shivering, which occurred more frequently in the misoprostol group (22.2% vs 5.7%; relative risk 4.73; 95% CI 2.31-9.68; P < 0.0001). CONCLUSIONS: In low risk women oral misoprostol appears to be as effective in minimising blood loss in the third stage of labour as intramuscular oxytocin. Shivering was noted more frequently with misoprostol use, but no other side effects were noted. Misoprostol has great potential for use in the third stage of labour especially in developing countries.

Mild traumatic brain injury--the Fife perspective.

Results are reported from a study to identify patients residing in Fife with mild traumatic brain injury in the 16-65 year old age group, who attended an accident and emergency department following their brain injury. Over a two month period 161 such patients attended with minor head trauma, of which 33 entered our study. The major cause of mild traumatic brain injury was assault. We found that over two-thirds of patients in the study had persisting post-concussive symptoms six months post injury. Neuropsychological testing showed problems of concentration and memory, but not at a level that was significantly different from that expected in an average population. Other studies have shown that symptom rates are higher when patients get no explanation of their symptoms and we feel that better co-ordination of services for brain injured patients in Fife is required, to provide the necessary information, education and support.

Training traditional birth attendants in Nigeria--the pictorial method.

High maternal mortality and morbidity rates are a challenge for all involved in the care of mothers and babies. One response takes the form of an educational programme led by professional midwives to teach traditional birth attendants to recognize risk conditions and improve their care of mothers and babies. Such a programme was organized as part of a Canadian-Nigerian safe motherhood initiative, and carried out in Akwa Ibom State, Nigeria.

Effects of hydrochlorothiazide and captopril on the survival and heart weight of cardiomyopathic hamsters.

The current study investigated the effect of hydrochlorothiazide (HCTZ), and of captopril, on the survival and heart weight of cardiomyopathic hamsters (CMH). Groups of 51 CMH (about 200 days old) were orally treated with HCTZ (6 mg/kg), captopril (30 mg/kg), a combination of both drugs or vehicle alone (control group), for 217 days. Then survivors were sacrificed and the hearts weighed. The survival of the animals treated with HCTZ alone or in combination with captopril was similar, and was clearly increased when compared to controls (more than 70 days increase in median survival time). A more modest increase in survival occurred in animals treated with captopril alone. The efficacy of the diuretic therapy was consistent with fluid retention being the primary cause of death in CMH and demonstrated the usefulness of the model for the testing of new diuretics. HCTZ or captopril alone had no effect on the heart weight of survivors. However a reduction of cardiac hypertrophy (-18%) was seen when captopril and HCTZ were coadministered. This effect of the ACE inhibitor was considered to result from antagonism of the compensatory activation of the renin-angiotensin system occurring in response to diuretic therapy.

Early interference in a priming task with brief masked targets.

Priming effects were examined in two experiments using either a pronunciation or lexical decision task. The prime, either a strong associate of the target, an unrelated word, or a neutral prime, was presented for 200 ms. After an SOA of 200, 400, or 800 ms, a masked target was presented for 33.3, 50, or 66.7 ms. Attention was manipulated by varying the probability that prime and target would be strongly associated. Both experiments showed significant interference in the low attention condition and at the 200-ms SOA, presumably before the onset of consciously directed processing. Two subsequent experiments using a short SOA and the low attention condition attempted to determine the conditions under which this interference will occur by varying the interstimulus interval, target duration, and the mask. It was found that interference occurred only when targets were brief and masked. These results are discussed in terms of a model involving lateral inhibition between nodes in semantic memory. It is suggested that when the target is brief and masked, the node in memory corresponding to the target is much less strongly activated and therefore more susceptible to the inhibitory effects of other activated nodes.

Effect of low-intensity hippocampal stimulation on spatial versus working memory in rats.

A series of experiments was performed to investigate differing predictions from the spatial mapping hypothesis of hippocampal function proposed by O'Keefe and Nadel (1978) and the working memory hypothesis proposed more recently by Olton and his colleagues (Olton, Becker, & Handelmann, 1979). Each of two groups of rats was trained to use a different strategy to locate a submerged platform in a tank of opaque water. The MAP group used a spatial mapping strategy to reach a platform in a fixed location over trials; whereas the CUE group used a guidance strategy, which involved following a cue that signaled the location of a randomly placed platform on each trial. Following acquisition, one-half of each group was given low-level unilateral electrical stimulation of the dentate gyrus and immediately tested on the water maze task. The results of Experiment 1 showed that both the MAP and CUE groups were impaired by stimulation. However, it was observed that there was an inadvertent spatial element involved in the CUE task. When this element was eliminated in Experiment 3, the same CUE animals were not affected by a second series of stimulation trials, whereas the MAP animals continued to show impairment. These results are interpreted as strongly supporting the cognitive mapping hypothesis, while at the same time providing little support for the working memory hypothesis of hippocampal function.

Specific and nonspecific changes in visual evoked potentials during eyelid conditioning in the rabbit (Oryctolagus cuniculus).

Eye blinks were conditioned to either the visual or nonvisual element of a compound conditioned stimulus. The visual element consisted of a series of electrical pulses to the optic chiasma, and the averaged evoked potentials (AEPs) produced by this stimulus were recorded in the dorsal lateral geniculate nucleus and the visual cortex. The initial surface positive component of the cortical AEP was enhanced only when the eye blinks were conditioned to the visual stimulus, an effect that cannot be attributed to nonspecific mechanisms. The "postsynaptic" component of the geniculate AEP was also enhanced, but this occurred regardless of whether the eye blinks were conditioned to the visual or nonvisual stimulus, an effect that appears to be entirely nonspecific. Data from recovery cycles indicate that this enhancement effect cannot be attributed to an inhibition of inhibitory interneurons in the lateral geniculate nucleus.

Methylphenidate, amygdalectomy, and active avoidance performance in the rat.

Amygdalectomized and control rats were given 400 active avoidance training trials in a shuttle box. Control animals received 0, 4, 8, or 16 mg/kg of methylphenidate throughout acquisition. Amygdalectomized animals were given the first 200 trials without drug, followed by 200 trials with drug. The administration of methylphenidate produced an abrupt and large improvement in performance in the amygdalectomized animals. One month after acquisition under the drug, retraining without drug revealed a significant retention effect for the three amygdaloid-drug groups relative to the nondrug-amygdaloid group. These results indicate that although amygdalectomy impairs the performance of avoidance responses, it does not prevent the learning or retention of such responses. Since methylphenidate appears to act primarily on dopaminergic mechanisms, the possible influence of amygdalectomy on such mechanisms is discussed.

Ventilation and cardiovascular studies during mechanical control of ventilation in horses.

Eleven out of 12 horses were underventilating while breathing spontaneously during halothane anaesthesia with high arterial carbon dioxide tensions. In addition, large alveolar to arterial oxygen tension gradients were found to be present. Mechanically, controlled ventilation with an intermittent positive pressure of 20-30 cm H2O reduced arterial carbon dioxide levels to normal. The alveolar to arterial oxygen gradients did not increase and in some cases decreased. These (A - a) Po2 gradients were due mainly to true shunt of the order of 30 per cent and not to ventilation perfusion inequality.