Effects of video-feedback intervention on harmonious parent-child interaction and sensitive discipline of parents with intellectual disabilities: A randomized controlled trial.

BACKGROUND: This study tested whether video-feedback intervention based on attachment and coercion theory increased harmonious parent-child interaction and sensitive discipline of parents with mild intellectual disabilities or borderline intellectual functioning. METHODS: Observer ratings of video-recorded structured interaction tasks at home formed pretest, post-test, and 3-month follow-up outcome data in a randomized controlled trial with 85 families. Repeated measures analyses of variance and covariance were conducted to test for the intervention effect and possible moderation by IQ and adaptive functioning. RESULTS: The intervention effect on harmonious parent-child interaction was conditional on parental social adaptive behaviour at pretest, with lower adaptive functioning associated with stronger intervention benefit at post-test and follow-up compared to care as usual. Intervention effects were not conditional on parental IQ. Intervention effects for sensitive discipline were not found. CONCLUSION: Although the video-feedback intervention did not affect observed parenting for the average parent, it may benefit interaction between children and parents with lower parental adaptive functioning.

A brief psychological intervention for mothers of children with food allergy can change risk perception and reduce anxiety: Outcomes of a randomized controlled trial.

BACKGROUND: Mothers of children with food allergy have increased anxiety, which may be influenced by healthcare professionals' communication of risk. OBJECTIVE: To evaluate a brief psychological intervention for reducing anxiety in mothers of children with food allergy. METHODS: Two hundred mothers of children with food allergy were recruited from allergy clinics. A computer-generated randomization list was used to allocate participants to a single-session cognitive behavioural therapy intervention including a risk communication module, or standard care. Anxiety and risk perception were assessed at 6 weeks and 1 year. Primary outcome was state anxiety at 6 weeks. Secondary outcomes included state anxiety at 1 year, risk perception at 6 weeks and 1 year, and salivary cortisol response to a simulated anaphylaxis scenario at 1 year. RESULTS: We found no significant difference in the primary outcome state anxiety at 6 weeks, with mean 31.9 (SD 10.2) intervention, 34.0 (10.2) control; mean difference 2.1 (95% CI -0.9, 5.0; P=.17). There was significantly reduced state anxiety at 6 weeks in the intervention group, in the subgroup of participants with moderate/high anxiety at enrolment (103/200, 52%), with mean 33.0 (SD 9.3) intervention, 37.8 (SD 10.0) control; mean difference 4.8 (95% CI 0.9, 8.7; P=.016; Cohen's d effect size 0.50). The psychological intervention also reduced risk perception and salivary cortisol response (P=.032; effect size 0.36). CONCLUSION: We found evidence that a brief psychological intervention which incorporates accurate risk information may impact on anxiety, risk perception and physiological stress response in mothers of children with food allergy.

Incidence of food anaphylaxis in people with food allergy: a systematic review and meta-analysis.

BACKGROUND: Food allergy is a common cause of anaphylaxis, but the incidence of anaphylaxis in food allergic people is unknown. METHODS: We undertook a systematic review and meta-analysis, using the inverse variance method. Two authors selected studies by consensus, independently extracted data and assessed study quality using the Newcastle-Ottawa assessment scale. We searched Medline, Embase, PsychInfo, CINAHL, Web of Science, LILACS and AMED between January 1946 and September 2012 and recent conference abstracts. We included registries, databases or cohort studies which described the number of food anaphylaxis cases in a defined population and time period and applied an assumed population prevalence of food allergy. RESULTS: We included data from 34 studies. There was high heterogeneity between study results, possibly due to variation in study populations, anaphylaxis definition and data collection methods. In food allergic people, medically coded food anaphylaxis had an incidence rate of 0.14 per 100 person-years (95% CI 0.05, 0.35; range 0.01, 1.28). In sensitivity analysis using different estimated food allergy prevalence, the incidence varied from 0.11 to 0.21 per 100 person-years. At age 0-19, the incidence rate for anaphylaxis in food allergic people was 0.20 (95% CI 0.09, 0.43; range 0.01, 2.55; sensitivity analysis 0.08, 0.39). At age 0-4, an incidence rate of up to 7.00 per 100 person-years has been reported. In food allergic people, hospital admission due to food anaphylaxis had an incidence rate of 0.09 (95% CI 0.01, 0.67; range 0.02, 0.81) per 1000 person-years; 0.20 (95% CI 0.10, 0.43; range 0.04, 2.25) at age 0-19 and 0.50 (0.26, 0.93; range 0.08, 2.82) at age 0-4. CONCLUSION: In food allergic people, the incidence of food allergic reactions which are coded as anaphylaxis by healthcare systems is low at all ages, but appears to be highest in young children.

Patients' ability to treat anaphylaxis using adrenaline autoinjectors: a randomized controlled trial.

BACKGROUND: Previous work has shown patients commonly misuse adrenaline autoinjectors (AAI). It is unclear whether this is due to inadequate training, or poor device design. We undertook a prospective randomized controlled trial to evaluate ability to administer adrenaline using different AAI devices. METHODS: We allocated mothers of food-allergic children prescribed an AAI for the first time to Anapen or EpiPen using a computer-generated randomization list, with optimal training according to manufacturer's instructions. After one year, participants were randomly allocated a new device (EpiPen, Anapen, new EpiPen, JEXT or Auvi-Q), without device-specific training. We assessed ability to deliver adrenaline using their AAI in a simulated anaphylaxis scenario six weeks and one year after initial training, and following device switch. Primary outcome was successful adrenaline administration at six weeks, assessed by an independent expert. Secondary outcomes were success at one year, success after switching device, and adverse events. RESULTS: We randomized 158 participants. At six weeks, 30 of 71 (42%) participants allocated to Anapen and 31 of 73 (43%) participants allocated to EpiPen were successful - RR 1.00 (95% CI 0.68-1.46). Success rates at one year were also similar, but digital injection was more common at one year with EpiPen (8/59, 14%) than Anapen (0/51, 0%, P = 0.007). When switched to a new device without specific training, success rates were higher with Auvi-Q (26/28, 93%) than other devices (39/80, 49%; P < 0.001). CONCLUSIONS: AAI device design is a major determinant of successful adrenaline administration. Success rates were low with several devices, but were high using the audio-prompt device Auvi-Q.

Parenting stress and child behaviour problems among parents with intellectual disabilities: the buffering role of resources.

BACKGROUND: Parents with intellectual disabilities (ID) are at risk for high levels of parenting stress. The present study evaluated resources, including parental adaptive functioning, financial resources and access to a support network, as moderators of the association between child behaviour problems and parenting stress. METHOD: A total of 134 parents with ID and their children (ages 1-7 years) were recruited from 10 Dutch care organisations. Questionnaires were administered to the parents to obtain information on parenting stress in the parent and child domain, financial resources and their support network. Teachers and care workers reported on child behaviour problems and parental adaptive functioning, respectively. RESULTS: Parents experienced more stress with regard to their children than towards their own functioning and situation. Parenting stress was less in parents who were not experiencing financial hardship. Child behaviour problems were associated with high child-related parenting stress, not parent-related parenting stress. Large support networks decreased the association between child behaviour problems and child-related parenting stress. Financial resources did not significantly moderate the association. CONCLUSIONS: Parenting stress among parents with ID is focused on problems with the child, especially when little social support is available.

Incidence of fatal food anaphylaxis in people with food allergy: a systematic review and meta-analysis.

BACKGROUND: Food allergy is a common cause of anaphylaxis, but the incidence of fatal food anaphylaxis is not known. The aim of this study was to estimate the incidence of fatal food anaphylaxis for people with food allergy and relate this to other mortality risks in the general population. METHODS: We undertook a systematic review and meta-analysis, using the generic inverse variance method. Two authors selected studies by consensus, independently extracted data and assessed the quality of included studies using the Newcastle-Ottawa assessment scale. We searched Medline, Embase, PsychInfo, CINAHL, Web of Science, LILACS or AMED, between January 1946 and September 2012, and recent conference abstracts. We included registries, databases or cohort studies which described the number of fatal food anaphylaxis cases in a defined population and time period and applied an assumed population prevalence rate of food allergy. RESULTS: We included data from 13 studies describing 240 fatal food anaphylaxis episodes over an estimated 165 million food-allergic person-years. Study quality was mixed, and there was high heterogeneity between study results, possibly due to variation in food allergy prevalence and data collection methods. In food-allergic people, fatal food anaphylaxis has an incidence rate of 1.81 per million person-years (95%CI 0.94, 3.45; range 0.63, 6.68). In sensitivity analysis with different estimated food allergy prevalence, the incidence varied from 1.35 to 2.71 per million person-years. At age 0-19, the incidence rate is 3.25 (1.73, 6.10; range 0.94, 15.75; sensitivity analysis 1.18-6.13). The incidence of fatal food anaphylaxis in food-allergic people is lower than accidental death in the general European population. CONCLUSION: Fatal food anaphylaxis for a food-allergic person is rarer than accidental death in the general population.

Psychological distress and mental health service contact of unaccompanied asylum-seeking children.

BACKGROUND: Evidence is emerging that psychological problems, particularly symptoms of depression and post-traumatic stress disorder, are more prevalent in unaccompanied asylum-seeking children (UASC) than their accompanied peers. However, little is known about help seeking and mental health service (MHS) utilization in this group, and how this relates to their psychological needs. This study aims to describe the level of psychological distress among a group of UASC and the pattern of MHS contact. METHOD: Socio-demographic data on 71 UASC residing in London was obtained and self-report questionnaires were completed regarding trauma events (Harvard Trauma Questionnaire), general psychological distress [Strengths and Difficulties Questionnaire (SDQ)], post-traumatic stress symptoms (Impact of Event Scale), depressive symptoms (Birleson Depression Self-Rating Scale for Children) and contact with MHS (Attitudes to Health and Services Questionnaire). RESULTS: UASC were mainly male (n = 48, 67.6%), Black African (n = 39, 54.9%) and their median age was 17 years (interquartile range = 15; 17). They had been living in the UK for a median of 18 months. Eight (11.3%) scored on the SDQ borderline/abnormal range for total symptoms, but this was 21 (29.6%) using the SDQ emotional subscale. Forty-seven (66.2%) were at high risk for post-traumatic stress disorder and nine (12.7%) at high risk for depressive disorder. Only 12 (17%) had MHS contact. Predictors of MHS contact were depressive symptoms and duration of time in the UK. CONCLUSIONS: UASC had a high level of emotional symptoms, especially post-traumatic stress symptoms. However, only a small proportion of UASC were in contact with MHS. This suggests a high level of MHS under-utilization, and reasons for this are discussed.

Linkage of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease to the prion protein gene.

The Indiana kindred variant of Gerstmann-Sträussler-Scheinker disease has amyloid plaques that contain prion protein (PrP), but is atypical because neurofibrillary tangles like those of Alzheimer disease are present. To map the position of the disease causing gene, we used three markers for linkage analyses. A missense mutation at codon 198 of the PrP gene (PRNP) is found in all definitely affected individuals and yields a maximum lod score of 6.37 (theta = 0). The disease also is concordant with the two other PRNP-region markers. These results demonstrate tight linkage of the disease-causing gene to PRNP and support the hypothesis that the codon 198 mutation is the cause of IK-GSS. Our studies also suggest that methionine/valine heterozygotes at PRNP codon 129 have a later age of onset of the disease than codon 129 valine/valine homozygotes.

Mutant prion proteins in Gerstmann-Sträussler-Scheinker disease with neurofibrillary tangles.

Two families with Gerstmann-Sträussler-Scheinker disease (GSS) are atypical in possessing neocortical neurofibrillary tangles (NFTs), which are few or absent in other kindreds with GSS, in addition to amyloid plaques that react with prion protein (PrP) antibodies and protease-resistant PrP accumulation in the brain. A leucine substitution at PrP codon 102 has been genetically linked to GSS in some families. We examined the PrP gene in these families. A serine for phenylalanine substitution was found at codon 198 in the Indiana patients; arginine for glutamine substitution at codon 217 in the Swedish patients. These mutations in PrP are the first to be associated with the appearance of both PrP amyloid plaques and neocortical NFTs in GSS patients.

Ethnic factors in mental health service utilisation among people with intellectual disability in high-income countries: systematic review.

BACKGROUND: An emerging literature suggests that ethnic and cultural factors influence service utilisation among people with intellectual disability (ID), but this has not previously been reviewed. AIMS: To investigate possible ethnic variation in uptake of mental health services in children, adolescents and adults with ID in high-income countries. METHOD: A systematic review using main databases of studies that consider ethnic influences on mental health utilisation of people with ID. Methodological quality of studies was assessed. RESULTS: Nine studies that reached selection criteria were identified. Six studies that compared two or more ethnic groups found a variation in levels of mental health service utilisation. The most consistent finding was that South Asian children, adolescents and adults with ID in the UK had lower use of mental health services than White British comparison groups. CONCLUSION: Ethnic influences on mental health service utilisation were identified. Understanding their significance and potential negative consequences requires further investigation.

Ethnic variation in service utilisation among children with intellectual disability.

BACKGROUND: This study examined whether service utilisation among children with intellectual disability (ID) varied by ethnic cultural group. METHOD: Survey carried out in four special schools in London. Information was provided by school teachers using case files, and 242 children aged 7 to 17 years with mild and moderate ID were identified. Ethnic categories were derived from self-reported main categories. Service utilisation categorised as use of: child and adolescent mental health services (CAMHS), social services, physical health and education services. RESULTS: Child and adolescent mental health services uptake was lower for South Asians than for White British (P = 0.0487). There were statistically significant differences among ethnic groups for community-based social services uptake (being the highest for the Black groups and the lowest for South Asians, P = 0.015) and respite care uptake (being the highest for the Black and White European groups and the lowest for South Asians, P = 0.009). In regression analysis family structure predicted CAMHS service utilisation and social service community support. Ethnicity predicted use of respite care. CONCLUSIONS: Significant ethnic differences in service utilisation among children with ID were found for both CAMHS and social service contact. There was particularly low service use for the South Asian group. These differences might arise because of differences in family organisation, as more South Asian children lived in two-parent families, which may have been better able to provide care than single-parent families. Other factors such as variation in parental belief systems and variation in psychopathology may be relevant. Implications are discussed.

Proteolipid protein is necessary in peripheral as well as central myelin.

Alternative products of the proteolipid protein gene (PLP), proteolipid protein (PLP) and DM20, are major components of compact myelin in the central nervous system, but quantitatively minor constituents of Schwann cells. A family with a null allele of PLP has a less severe CNS phenotype than those with other types of PLP mutations. Moreover, individuals with PLP null mutations have a demyelinating peripheral neuropathy, not seen with other PLP mutations of humans or animals. Direct analysis of normal peripheral nerve demonstrates that PLP is localized to compact myelin. This and the clinical and pathologic observations of the PLP null phenotype indicate that PLP/DM20 is necessary for proper myelin function both in the central and peripheral nervous systems.

Shope papilloma virus. II. A comparison of several methods for purification of the virus.

Four methods for preparation of Shope papilloma virus have been compared. These comprise: (1) alternate centrifugation at low and high speed after grinding with alundum and saline, (2) purification with a fluorocarbon after similar extraction, (3) extraction with the aid of 2-mercaptoethanol and purification by alternate low- and high-speed centrifugation, and (4) extraction with 2-mercaptoethanol followed immediately by centrifugation to equilibrium in CsCI. It is necessary to remove CsCI before chemical analysis, and this has been accomplished by chromatography on Sephadex G-75. After banding, the virus from preparation (4) appears homogeneous in the electron microscope. The deoxyribonucleic acid (DNA) contents of the preparations were (1) 7.8, (2) 8.3, (3) 8.0, and (4) 11.9 percent of total nucleoprotein. At equal inputs of DNA, there was no significant difference in infectivity of any of the preparations. Method (4) is simpler than the others and results in a higher yield of a homogeneous preparation.

In situ hybridization analysis of Girk2 expression in the developing central nervous system in normal and weaver mice.

A mutation in the gene Girk2 that encodes an inwardly rectifying potassium channel is the genetic defect causing the behavioral and pathologic abnormalities of the weaver mutant mouse. Of the pathologic abnormalities, the best studied is the neuronal degeneration that occurs in the cerebellar cortex and in the midbrain dopaminergic neurons. A detailed characterization of the topographic and temporal expression of Girk2 is fundamental to elucidate the mechanisms underlying neurodegeneration in these mutant mice. In this study we utilized in situ hybridization to determine the expression of Girk2 mRNA during prenatal and postnatal development in the murine central nervous system (CNS). Girk2 expression was seen in multiple regions of embryonic CNS including the cerebellum and midbrain. During postnatal development, the highest expression was seen in the cerebellum, midbrain and hippocampus. However, since the developing cerebellum undergoes significant neuronal loss due to the degeneration of granule cell precursors, Girk2 mRNA expression in this area decreases progressively.

Coupled reverse transcription-polymerase chain reaction (RT-PCR) as a sensitive and rapid method for isozyme genotyping.

We have developed a highly sensitive and rapid coupled reverse transcription-polymerase chain reaction (RT-PCR) technique for detection of alpha-amylase-encoding gene transcripts and for distinguishing between the human salivary (AMY1) and pancreatic (AMY2) gene transcripts. The two genes are 93-94% homologous. However, the AMY1 gene has an additional exon known as exon S, and an extra 32 bp in exon 1. Genotyping of the different AMYs by RT-PCR was based on this unique feature of the AMY1 mRNA sequence. Detection of AMY gene (AMY1 and AMY2) transcripts in cellular RNA was achieved with a set of primers common to both human AMY1 and AMY2 genes and derived from the exon 3-4 regions. In contrast, AMY1 gene transcripts were distinguished from the pancreatic AMY2 gene transcripts by use of primers specific to the exon S-1 regions of the AMY1 gene. To distinguish AMY1 transcripts from a mixture of AMY1 and AMY2, use was made of the differences in the ethidium bromide-stained agarose gel patterns obtained after digestion of the amplified exon 3-4 fragments with TaqI. AMY gene transcripts were detectable by autoradiography in RT-PCR amplified DNA obtained from as little as 5 pg of human pancreatic or parotid total RNA. A comparison of sensitivity of Northern blotting vs. RT-PCR suggested that the RT-PCR method is about 3-6 x 10(3)-fold more sensitive than Northern blotting in detecting AMY gene transcripts in human pancreatic total RNA.

The weaver mutation changes the ion selectivity of the affected inwardly rectifying potassium channel GIRK2.

The weaver mutation in mice has recently been identified as a single base-pair mutation in the Girk2 gene, which encodes a G-protein-activated inwardly rectifying potassium channel, GIRK2. The mutation results in a Gly to Ser substitution at residue 156, in the putative pore-forming region of the potassium channel. In the present study, we used Xenopus oocytes to express mutant GIRK2, and to characterize the effects of the mutation on the channel. The mutation results in a loss of the normal high selectivity for K+ over Na+, with little effect on other channel properties such as activation by the mu opioid receptor. The resulting increase in basal Na+ permeability causes a marked depolarization of oocytes expressing the mutant GIRK2 protein. This result was observed even when the mutant GIRK2 was coexpressed with GIRK1, a situation more analogous to that seen in vivo. Thus, the increased Na+ permeability and resulting depolarization may contribute to the pathology of cerebellar granule cells and substantia nigra dopaminergic neurons observed in the weaver mice.

Motor changes in presymptomatic Huntington disease gene carriers.

OBJECTIVE: To determine whether changes in motor function and reaction time are present in presymptomatic individuals carrying the Huntington disease (HD) allele. DESIGN: A case-control, double-blind study comparing asymptomatic at-risk subjects, with or without the HD allele, and subjects clinically determined to have early manifest HD. SETTING: The Department of Medical and Molecular Genetics at Indiana University School of Medicine, Indianapolis. PARTICIPANTS: We studied 383 patients at risk for HD. Each subject was asymptomatic by self-report. MEASURES: Genotype for the HD allele was determined by polymerase chain reaction testing. A battery of 8 physiological tests measuring speed of movement and reaction time was performed with a computer-driven system. RESULTS: Following neurologic examination, 17 of the 120 gene carriers (GCs) had symptoms sufficient for a clinical diagnosis of manifest HD. The remaining 103 GCs were designated presymptomatic GCs. When the non-GCs were compared with the presymptomatic GCs (1-way analysis of covariance and the Fisher protected t test), results on 3 of the 8 physiological tests--movement time, movement time with decision, and auditory reaction time--were different. Additionally, the number of trinucleotide (CAG) repeats significantly correlated with test performance for movement time with decision and visual reaction time with decision when both the entire group of GCs and the presymptomatic GCs alone were considered. CONCLUSION: These results suggest that subtle subclinical changes in motor function are present in presymptomatic individuals who have inherited the HD allele.

Longitudinal cognitive and motor changes among presymptomatic Huntington disease gene carriers.

OBJECTIVE: To determine whether longitudinal changes in cognitive and motor function can be detected among clinically presymptomatic individuals carrying the Huntington disease (HD) allele. DESIGN: A longitudinal, case-control, double-blind study comparing presymptomatic gene carriers and non-gene carriers at risk for HD examined an average of 3.7 years apart. SETTING: The Department of Medical and Molecular Genetics at a general clinic research center in Indianapolis, Ind. PARTICIPANTS: A sample of 43 at-risk individuals consisting of presymptomatic gene carriers (n = 12) and non-gene carriers (n = 31). MEASURES: Huntington disease gene status was determined by molecular testing of the HD gene. Subscales from the Wechsler Adult Intelligence Scale-Revised and a quantified neurologic rating scale were administered. RESULTS: Scores on the digit symbol subscale of the Wechsler Adult Intelligence Scale-Revised (P<.05) and 2 neurologic variables-optokinetic nystagmus (P<.01) and rapid alternating movements (P<.005)-declined more rapidly among presymptomatic gene carriers than among non-gene carriers. At follow-up examination, compared with nongene carriers, presymptomatic gene carriers had significantly lower scores on the digit symbol subscale (P = .02) and for 4 neurologic variables-rapid alternating movements (P<.005), optokinetic nystagmus (P<.001), overall ocular movements (P<.02), and chorea of the trunk (P<.02). CONCLUSIONS: Psychomotor speed, optokinetic nystagmus, and rapid alternating movements demonstrated significant decline early in the pathological process of HD. These results suggest that subtle worsening of psychomotor, oculomotor, and motor functions occurs before the onset of signs sufficient to make a clinical diagnosis in individuals who have inherited the HD allele.

X-linked recessive inheritance of ataxia and adult-onset dementia: clinical features and preliminary linkage analysis.

Three generations of a family exhibit a unique syndrome of X-linked ataxia, pyramidal tract signs, and adult-onset dementia. Initial signs, manifested by 2 to 3 years of age, are delayed walking and tremor. During their teens, the patients develop mild but progressive ataxia and pyramidal tract signs. Memory problems in the third decade initiate a progressive dementia, leading to death in the sixth decade. Laboratory investigations failed to disclose a biochemical basis for the syndrome. Preliminary molecular linkage studies have been conducted, and although the specific position of the responsible gene on the X chromosome has not yet been determined, the q26-qter region and much of the p arm are unlikely sites for this gene. The linkage studies are continuing.

Adult-onset neurodegenerative disorder due to proteolipid protein gene mutation in the mother of a man with Pelizaeus-Merzbacher disease.

A 23-year-old man with Pelizaeus-Merzbacher disease had a novel mutation, C344A (Thr115Lys), in exon 3 of the proteolipid protein gene (PLP) His mother, heterozygous for the mutation, developed progressive personality change and a gait disorder in her mid-20s. Her MRI at age 53 showed a diffuse severe leukodystrophy. This report extends the phenotypic range of disease due to PLP gene mutations to include adult-onset dementia in females.