Doubling daily inhaled corticosteroid dose is ineffective in mild to moderately severe attacks of asthma in adults

Background: Asthma guidelines recommend increasing or doubling inhaled corticosteroid (ICS) dose to treat mild and moderate exacerbations of asthma in adults. Aim: To: (i) compare the effectiveness of doubling existing daily ICS dose (fluticasone) with maintaining usual ICS dose and usual daily ICS dose accompanied by oral steroids (OS) (dexamethasone) during mild and moderately severe exacerbations of asthma in adults; (ii) examine determinants of success and failure; and (iii) compare side-effect profiles. Methods: A randomized, double-blind, placebo-controlled (double-dummy), triple crossover trial. Participants acted as their own control. Outcome measures included treatment success/failure, peak expiratory flow (PEF) after 7 days therapy or at treatment failure, and side-effects. Results: From 22 participants (nine males and 13 females), 18 pairs of data were available for maintaining usual ICS versus doubling ICS and doubling ICS versus OS, and 19 for maintaining usual ICS versus OS. Median (fifth-95th percentile) age was 46.5 (32-64) years and forced expiratory volume in one second (FEV1) 73% (29-97%) predicted. The outcome after doubling ICS was not superior to maintaining usual ICS, with 11 (61%) failures in both arms (P = 0.66). OS, with only 5 (26%) failures, was superior to maintaining usual ICS with 12 (63%) failures (P = 0.04), and to doubling ICS with 5 (28%) versus 11 (61%) failures (P = 0.07). Median PEF (as percentage of run-in best) at end-points were 90.5% (57.1-177.1) for OS, 78.3% (39.5-103.1) for maintaining usual ICS and 77.9 (27.7-110.3) for doubling ICS. Neither gender nor PEF at exacerbation were predictive of failure. Although doubling ICS was not an effective therapy overall, ICS dose at exacerbation were predictive of success in the doubling ICS arm (P = 0.04). Treatment failures when doubling daily ICS dose were more common if achieved fluticasone dose was less than 2000 mu g (three of 11, 73%) compared to 2000 mu g or greater (eight of eight, 37.5%). Increasing age and the presence of an upper respiratory tract infection (URTI) were predictive of failure with OS. Side-effects were more commonly reported with OS (52.6%) than doubling ICS (42.1%) or maintaining usual ICS (19.1%) with the most common being mood changes (36.8%), sleep disturbance (31.6%) and changes in appetite (26.3%). Conclusions: Doubling daily ICS dose per se is not effective for the treatment of mild to moderately severe exacerbations of asthma in adults. Success may depend on achieved ICS dose. Oral steroids are effective, but side-effects are common. A review of current guidelines may be warranted.

The effectiveness of aphasia-friendly principles for printed health education materials for people with aphasia following stroke

Background: Provision of health information to people with aphasia is inadequate. Current practice in providing printed health education materials to people with aphasia does not routinely take into consideration their language and associated reading difficulties. Aims: This study aimed to investigate if people with aphasia can comprehend health information contained in printed health education materials and if the application of aphasia-friendly principles is effective in assisting them to comprehend health information. It was hypothesised that participants with aphasia would comprehend significantly more information from aphasia-friendly materials than from existing materials. Other aims included investigating if the effectiveness of the aphasia-friendly principles is related to aphasia severity, if people with aphasia are more confident in responding to health information questions after they have read the aphasia-friendly material, if they prefer to read the aphasia-friendly brochures, and if they prefer to read the brochure type that resulted in the greatest increase in their knowledge. Methods & Procedures: Twelve participants with mild to moderately severe aphasia were matched according to their reading abilities. A pre and post experimental design was employed with repeated measures ANOVA (p

Latent class and genetic analysis does not support migraine with aura and migraine without aura as separate entities

Latent class and genetic analyses were used to identify subgroups of migraine sufferers in a community sample of 6,265 Australian twins (55% female) aged 25-36 who had completed an interview based on International Headache Society UHS) criteria. Consistent with prevalence rates from other population-based studies, 703 (20%) female and 250 (9%) male twins satisfied the IHS criteria for migraine without aura (MO), and of these, 432 (13%) female and 166 (6%) male twins satisfied the criteria for migraine with aura (MA) as indicated by visual symptoms. Latent class analysis (LCA) of IHS symptoms identified three major symptomatic classes, representing 1) a mild form of recurrent nonmigrainous headache, 2) a moderately severe form of migraine, typically without visual aura symptoms (although 40% of individuals in this class were positive for aura), and 3) a severe form of migraine typically with visual aura symptoms (although 24% of individuals were negative for aura). Using the LCA classification, many more individuals were considered affected to some degree than when using IHS criteria (35% vs. 13%). Furthermore, genetic model fitting indicated a greater genetic contribution to migraine using the LCA classification (heritability, h(2) =0.40; 95% CI, 0.29-0.46) compared with the IHS classification (h(2)=0.36; 95% CI, 0.22-0.42). Exploratory latent class modeling, fitting up to 10 classes, did not identify classes corresponding to either the IHS MO or MA classification. Our data indicate the existence of a continuum of severity, with MA more severe but not etiologically distinct from MO. In searching for predisposing genes, we should therefore expect to find some genes that may underlie all major recurrent headache subtypes, with modifying genetic or environmental factors that may lead to differential expression of the liability for migraine. (C) 2004 Wiley-Liss, Inc.

The rellationship between specific features of aphasia-friendly written material and comprehension of written material for people with aphasia: An exploratory study

Background: Written material is often inaccessible fro people with aphasia. The format of written material needs to be adapted to enable people with aphasia to read with understanding. Aims: This study aimed to further explore some issues raised in Rose, Worrall, and MacKenna (2003) concerning the effects of aphasia-friendly formats on the reading comprehension of people with aphasia. It was hypothesised that people with aphasia would comprehend significantly more paragraphs that were formatted in an aphasia-friendly manner than control paragraphs. This study also aimed to investigate if each single aspect of aphasia-friendly formatting (i.e., simplified vocabulary and syntax, large print, increased white spacem and pictures) used in isolation would result in increased comprehension compared to control paragraphs. Other aims were to compare the effect of aphasia-friendly fromatting with the effects of each single adaptation, and to investigate if the effects of aphasia-friendly formates were related to aphasia severity. Methods & Procedures: Participants with mild to moderately severe aphasia (N = 9) read a battery of 90 paragraphs and selected the best word of phrase from a choice of four to complete each paragraph. A linear mixed model (p < .05) was used to analyse the differences in reading comprehension with each paragraph fromat across three reading grade levels. Outcomes & Results: People with aphasia comprehended significantly more aphasia-friendly paragraphs than control paragraphs. They also comprehended significantly more paragraphs with each of the following single adaptations: simplified vocabulary and syntax, large ptint, and increased white spaces. Although people with aphasia tended to comprehend more paragraphs with pictures added than control paragraphs, this difference was not significant. No significant correlation between aphasia severity and the effect of aphasia-friendly formatting was found. Conclusion: This study supports the idea that aphasia-friendly formats increase the reading comprehension of people with aphasia. It suggests that adding pictures, particularly Clip Art pictures, may not significantly improve the reading the reading comprehension of people with aphasia. These findings have implications for all written communication with people with aphasia, both in the clinical setting and in the wider community. Applying these findings may enable people with aphasia to have equal access to written information and to participate in society.

Migraine With Aura and Migraine Without Aura Are Not Distinct Entities: Further Evidence From a Large Dutch Population Study

It is often debated whether migraine with aura (MA) and migraine without aura (MO) are etiologically distinct disorders. A previous study using latent class analysis (LCA) in Australian twins showed no evidence for separate subtypes of MO and MA. The aim of the present study was to replicate these results in a population of Dutch twins and their parents, siblings and partners (N = 10,144). Latent class analysis of International Headache Society (IHS)-based migraine symptoms resulted in the identification of 4 classes: a class of unaffected subjects (class 0), a mild form of nonmigrainous headache (class 1), a moderately severe type of migraine (class 2), typically without neurological symptoms or aura (8% reporting aura symptoms), and a severe type of migraine (class 3), typically with neurological symptoms, and aura symptoms in approximately half of the cases. Given the overlap of neurological symptoms and nonmutual exclusivity of aura symptoms, these results do not support the MO and MA subtypes as being etiologically distinct. The heritability in female twins of migraine based on LCA classification was estimated at .50 (95% confidence intervals [0CI} .27 -.59), similar to IHS-based migraine diagnosis (h(2) = .49, 95% Cl .19-.57). However, using a dichotomous classification (affected-unaffected) decreased heritability for the IHS-based classification (h(2) = .33, 95% Cl .00-.60), but not the LCA-based classification (h(2) = .51, 95% Cl. 23-.61). Importantly, use of the LCA-based classification increased the number of subjects classified as affected. The heritability of the screening question was similar to more detailed LCA and IHS classifications, suggesting that the screening procedure is an important determining factor in genetic studies of migraine.

Clinical and molecular genetics of myoclonic-astatic epilepsy and severe myoclonic epilepsy in infancy (Dravet syndrome)

The majority of severe epileptic encephalopathies of early childhood are symptomatic where a clear etiology is apparent. There is a small subgroup, however, where no etiology is found on imaging and metabolic studies, and genetic factors are important. Myoclonic-astatic epilepsy (MAE) and severe myoclonic epilepsy in infancy (SMEI), also known as Dravet syndrome, are epileptic encephalopathies where multiple seizure types begin in the first few years of life associated with developmental slowing. Clinical and molecular genetic studies of the families of probands with MAE and SMEI suggest a genetic basis. MAE was originally identified as part of the genetic epilepsy syndrome generalized epilepsy with febrile seizures plus (GEFS(+)). Recent clinical genetic studies suggest that SMEI forms the most severe end of the spectrum of the GEFS(+). GEF(+) has now been associated with molecular defects in three sodium channel subunit genes and a GABA subunit gene. Molecular defects of these genes have been identified in patients with MAE and SMEI. Interestingly, the molecular defects in MAE have been found in the setting of large GEFS(+) pedigrees, whereas, more severe truncation mutations arising de novo have been identified in patients with SMEI. It is likely that future molecular studies will shed light on the interaction of a number of genes, possibly related to the same or different ion channels, which result in a severe phenotype such as MAE and SMEI. (C) 2001 Elsevier Science B.V. All rights reserved.

Sodium channel alpha 1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms

Background: Mutations in SCN1A, the gene encoding the alpha1 subunit of the sodium channel, have been found in severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS(+)). Mutations in SMEI include missense, nonsense, and frameshift mutations more commonly arising de novo in affected patients. This finding is difficult to reconcile with the family history of GEFS(+) in a significant proportion of patients with SMEI Infantile spasms (IS), or West syndrome, is a severe epileptic encephalopathy that is usually symptomatic. In some cases, no etiology is found and there is a family history of epilepsy. Method: The authors screened SCN1A in 24 patients with SMEI and 23 with IS. Results: Mutations were found in 8 of 24 (33%) SMEI patients, a frequency much lower than initial reports from Europe and Japan. One mutation near the carboxy terminus was identified in an IS patient. A family history of seizures was found in 17 of 24 patients with SMEI. Conclusions: The rate of SCN1A mutations in this cohort of SMEI patients suggests that other factors may be important in SMEI. Less severe mutations associated with GEFS(+) could interact with other loci to cause SMEI in cases with a family history of GEFS(+). This study extends the phenotypic heterogeneity of mutations in SCN1A to include IS.

A 1-year longitudinal study of severe traumatic brain injury in Australia using the Sickness Impact Profile

Objective: To document outcome and to investigate patterns of physical and psychosocial recovery in the first year following severe traumatic brain injury (TBI) in an Australian patient sample. Design: A longitudinal prospective study of a cohort of patients, with data collection at 3, 6, 9, and 12 months post injury. Setting: A head injury rehabilitation unit in a large metropolitan public hospital. Patients: A sample of 55 patients selected from 120 consecutive admissions with severe TBI. Patients who were more than 3 months post injury on admission, who remained confused, or who had severe communication deficits or a previous neurologic disorder were excluded. Interventions: All subjects participated in a multidisciplinary inpatient rehabilitation program, followed by varied participation in outpatient rehabilitation and community-based sen ices. Main Outcome Measures: The Sickness impact Profile (SIP) provided physical, psychosocial, and total dysfunction scores at each follow-up. Outcome at 1 year was measured by the Disability Rating Scale. Results: Multivariate analysis of variance indicated that the linear trend of recovery over time was less for psychosocial dysfunction than for physical dysfunction (F(1,51) = 5.87, P < .02). One rear post injury, 22% of subjects had returned to their previous level of employability, and 42% were able to live independently. Conclusions: Recovery from TBI in this Australian sample followed a pattern similar to that observed in other countries, with psychosocial dysfunction being more persistent. Self-report measures such as the SIP in TBI research are limited by problems of diminished self-awareness.

Effects of sampling opportunities on preference for adults with severe disabilities

A variable that appears to affect preference development is the exposure to a variety of options. Providing opportunities for systematically sampling different options is one procedure that can facilitate the development of preference, which is indicated by the consistency of selections. The purpose of this study was to evaluate the effects of providing sampling opportunities on the preference development for two adults with severe disabilities. Opportunities for sampling a variety of drink items were presented, followed by choice opportunities for selections at the site where sampling occurred and at a non-sampling site (a grocery store). Results show that the participants developed a definite response consistency in selections at both sites. Implications for sampling practices are discussed.

Moderately strong vorticity in a bathtub-type flow

Theoretical and numerical analysis is performed for an inviscid axisymmetric vortical bathtub-type flow. The level of vorticity is kept high so that the image of the flow on the radial-axial plane (r-z plane) is not potential. The most significant findings are: (1) the region of validity of the strong vortex approximation is separated from the drain by a buffer region, (2) the power-law asymptote of the stream function, specified by Delta Psi similar to r(4/3) Deltaz, appears near the axis when vorticity in the flow is sufficiently strong and (3) the local Rossby number in the region of the 4/3 power-law the initial vorticity level in the flow and the global Rossby number.