Generic utility health-related quality of life instruments are useful in assessing stroke outcome because they facilitate a broader description of the disease and outcomes, allow comparisons between ...diseases, and can be used in cost-benefit analysis. The aim of this study was to validate the Assessment of Quality of Life (AQoL) instrument in a stroke population.
Ninety-three patients recruited from the community-based North East Melbourne Stroke Incidence Study between July 13, 1996, and April 30, 1997, were interviewed 3 months after stroke. Validity of the AQoL was assessed by examining associations between the AQoL and comparator instruments: the Medical Outcomes Short-Form Health Survey (SF-36); London Handicap Scale; Barthel Index; National Institutes of Health Stroke Scale; and Irritability, Depression, Anxiety scale. Sensitivity of the AQoL was assessed by comparing AQoL scores from groups of patients categorized by severity of impairment and disability and with total anterior circulation syndrome (TACS) versus non-TACS. Predictive validity was assessed by examining the association between 3-month AQoL scores and outcomes of death or institutionalization 12 months after stroke.
Overall AQoL utility scores and individual dimension scores were most highly correlated with relevant scales on the comparator instruments. AQoL scores clearly differentiated between patients in categories of severity of impairment and disability and between patients with TACS and non-TACS. AQoL scores at 3 months after stroke predicted death and institutionalization at 12 months.
The AQoL demonstrated strong psychometric properties and appears to be a valid and sensitive measure of health-related QoL after stroke.
Abstract In this third and final part of our review of multiple sclerosis (MS) treatment we look at the practical day-to-day management issues that are likely to influence individual treatment ...decisions. Whilst efficacy is clearly of considerable importance, tolerability and the potential for adverse effects often play a significant role in informing individual patient decisions. Here we review the issues surrounding switching between therapies, and the evidence to assist guiding the choice of therapy to change to and when to change. We review the current level of evidence with regards to the management of women in their child-bearing years with regards to recommendations about treatment during pregnancy and whilst breast feeding. We provide a summary of recommended pre- and post-treatment monitoring for the available therapies and review the evidence with regards to the value of testing for antibodies which are known to be neutralising for some therapies. We review the occurrence of adverse events, both the more common and troublesome effects and those that are less common but have potentially much more serious outcomes. Ways of mitigating these risks and managing the more troublesome adverse effects are also reviewed. Finally, we make specific recommendations with regards to the treatment of MS. It is an exciting time in the world of MS neurology and the prospects for further advances in coming years are high.
Abstract In Part 2 of this three part review of multiple sclerosis (MS) treatment with a particular focus on the Australian and New Zealand perspective, we review the newer therapies that have ...recently become available and emerging therapies that have now completed phase III clinical trial programs. We go on to compare the relative efficacies of these newer and emerging therapies alongside the existing therapies. The effectiveness of β-interferon in the treatment of different stages and the different disease courses of MS is critically reviewed with the conclusion that the absolute level of response in term of annualised relapse rates (where relapses occur) and MRI activity are similar, but are disappointing in terms of sustained disability progression for progressive forms of the disease. Finally we review the controversial area of combination therapy for MS. Whilst it remains the case that we have no cure or means of preventing MS, we do have a range of effective therapies that when used appropriately and early in the disease course can have a significant impact on short term and longer term outcomes.
Abstract Multiple sclerosis (MS) is a potentially life-changing immune mediated disease of the central nervous system. Until recently, treatment has been largely confined to acute treatment of ...relapses, symptomatic therapies and rehabilitation. Through persistent efforts of dedicated physicians and scientists around the globe for 160 years, a number of therapies that have an impact on the long term outcome of the disease have emerged over the past 20 years. In this three part series we review the practicalities, benefits and potential hazards of each of the currently available and emerging treatment options for MS. We pay particular attention to ways of abrogating the risks of these therapies and provide advice on the most appropriate indications for using individual therapies. In Part 1 we review the history of the development of MS therapies and its connection with the underlying immunobiology of the disease. The established therapies for MS are reviewed in detail and their current availability and indications in Australia and New Zealand are summarised. We examine the evidence to support their use in the treatment of MS.
To evaluate the rate of return of disease activity after cessation of multiple sclerosis (MS) disease-modifying therapy.
This was a retrospective cohort study from 2 large observational MS ...registries: MSBase and OFSEP. Patients with relapsing-remitting MS who had ceased a disease-modifying therapy and were followed up for the subsequent 12 months were included in the analysis. The primary study outcome was annualized relapse rate in the 12 months after disease-modifying therapy discontinuation stratified by patients who did, and did not, commence a subsequent therapy. The secondary endpoint was the predictors of first relapse and disability accumulation after treatment discontinuation.
A total of 14,213 patients, with 18,029 eligible treatment discontinuation epochs, were identified for 7 therapies. Annualized rates of relapse (ARRs) started to increase 2 months after natalizumab cessation (month 2-4 ARR 0.47, 95% CI 0.43-0.51). Commencement of a subsequent therapy within 2-4 months reduced the magnitude of disease reactivation (mean ARR difference: 0.15, 0.08-0.22). After discontinuation of fingolimod, rates of relapse increased overall (month 1-2 ARR: 0.80, 0.70-0.89) and stabilized faster in patients who started a new therapy within 1-2 months (mean ARR difference: 0.14, -0.01 to 0.29). The magnitude of disease reactivation for other therapies was low but reduced further by commencement of another treatment 1-10 months after treatment discontinuation. Predictors of relapse were a higher relapse rate in the year before cessation, female sex, younger age, and higher EDSS score. Commencement of a subsequent therapy reduced both the risk of relapse (HR 0.76, 95% CI 0.72-0.81) and disability accumulation (0.73, 0.65-0.80).
The rate of disease reactivation after treatment cessation differs among MS treatments, with the peaks of relapse activity ranging from 1 to 10 months in untreated cohorts that discontinued different therapies. These results suggest that untreated intervals should be minimized after stopping antitrafficking therapies (natalizumab and fingolimod).
This study provides Class III that disease reactivation occurs within months of discontinuation of MS disease-modifying therapies. The risk of disease activity is reduced by commencement of a subsequent therapy.
A missense mutation of the γ2 subunit of the γ-aminobutyric acid A (GABAsubA) receptor has been linked to an inherited human generalized epilepsy. As synaptic inhibition in the human brain is largely ...mediated by the GABAsubA receptor, we tested the hypothesis that the GABRG2(R43Q) mutation alters cortical excitability. Fourteen subjects affected by the GABRG2(R43Q) mutation (5 males, mean age: 44 ± 15 years) and 24 controls (11 males, mean age: 38 ± 11 years) were studied with transcranial magnetic stimulation (TMS). To assess the specificity of the effect of the mutation, 4 additional family members unaffected by the GABRG2(R43Q) mutation (2 males, mean age: 41 ± 16 years) were included. Subjects affected by the GABRG2(R43Q) mutation demonstrated reduced net short-interval intracortical inhibition and increased intracortical facilitation assessed with paired-pulse stimulation. Subjects with the mutation had similar motor thresholds to controls both at rest and with weak voluntary activation. No significant differences were noted between groups in the cortical silent period. Our findings provide in vivo evidence for increased intracortical excitability in subjects affected by the GABRG2(R43Q) mutation. These findings are also likely to represent an important clue to the mechanisms linking this gene defect and the epilepsy phenotype.
Although a number of acute stroke interventions are of proven efficacy, there is uncertainty about their community benefits. We aimed to assess this within a defined population.
Eligibility for ...tissue plasminogen activator (tPA), aspirin, stroke unit management and neuroprotection were assessed among incident stroke cases within the community-based North East Melbourne Stroke Incidence Study.
Among 306,631 people, there were 645 incident strokes managed in hospital. When eligible patients were extrapolated to the Australian population, for every 1,000 cases, 46 (95% CI 17-69) could have been saved from death or dependency with stroke unit management, 6 (95% CI 1-11) by using aspirin, 11 (95% CI 5-17) or 10 (95% CI 3-16) by using tPA at 3 and 6 h, respectively.
Although tPA is the most potent intervention, management in stroke units has the greatest population benefit and should be a priority.
Handicap is rarely comprehensively examined after stroke. We examined handicap among 5-year stroke survivors from an 'ideal' stroke incidence study.
Survivors were assessed with the London Handicap ...Scale LHS, score range: 0 (greatest handicap) to 100 (least handicap). Multivariable regression was used to examine demographic, risk and stroke-related factors associated with handicap.
351 of 441 (80%) survivors were assessed. Those assessed were more often Australian born than those not assessed (p < 0.05). The mean LHS score was 73 (SD = 21). The greatest handicap was present for physical independence and occupation/leisure items. Handicap was associated with older age, manual occupations, smoking, initial stroke severity, recurrent stroke and mood disorders.
Reducing recurrent stroke, through better risk factor management, is likely to reduce handicap. The association between handicap and mood disorders, which are potentially modifiable, warrants further investigation.
Background
Specific information about the nature of recurrent events that occur after each subtype of index stroke may be useful for refining preventive therapies. We aimed to determine whether ...stroke recurrence rates, the pattern of subtype recurrence, and prescription of secondary prevention agents differed according to initial stroke subtype.
Methods
Multiple overlapping sources were used to recruit all first-ever stroke patients from a geographically defined region of Melbourne, Australia over a 3-year period from 1996 to 1999. Potential stroke recurrences (fatal and nonfatal) occurring within 2 years of the initial event were identified following patient interview and follow up of death records. Subjects were classified into the different Oxfordshire groups and the type of first-ever stroke was compared with recurrent stroke events.
Results
One thousand, three hundred and sixteen first-ever strokes were registered during the 3-year period (mean age 74·4 years). A total of 103 first recurrent stroke events (fatal and nonfatal) occurred among those with a first-ever ischemic stroke or intracerebral hemorrhage (ICH) during the 2-year follow-up period. The recurrent stroke subtype was different to the index stroke subtype in most (78%) patients. People with partial anterior circulation infarct had the greatest proportion of recurrences (13%), with a third of these being the more severe total anterior circulation infarct subgroup. The relative risk of ICH after an index lacunar infarct (LACI) compared with an index non-LACI was 4·06 (95% CI 1·10–14·97, P=0·038). Prescription of secondary prevention agents was greater at 2 years after stroke than at hospital discharge, and was similar between ischemic stroke subtypes.
Conclusion
Approximately 9% of people with first-ever stroke suffered a recurrent event, despite many being prescribed secondary prevention agents. This has implications for the uptake of current preventive strategies and the development of new strategies. The possibility that ICH is greater among index LACI cases needs to be confirmed.
Background
We studied the prevalence of neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) in Indigenous populations of Australia and New Zealand with the aim of assessing ...potential differences.
Methods
Cases of possible NMOSD and MS were collected from Australia and New Zealand. Clinical details, MR imaging, and serologic results were used to apply 2015 IPND diagnostic criteria for NMOSD and 2010 McDonald criteria for MS. Frequencies of self-determined ethnic ancestry were calculated for confirmed NMOSD, suspected NMOSD, and MS. Prevalence rates for NMOSD and MS according to ancestry were compared.
Results
There were 75 cases with NMOSD, 89 with suspected NMSOD, and 101 with MS. NMOSD cases were more likely to have Asian, Indigenous, or Other ancestry compared to suspected NMOSD or MS. There were no differences in the clinical phenotype of NMOSD seen in Indigenous compared to European ancestry populations. Per 100,000, the prevalence estimate for NMOSD in people with Māori ancestry was 1.50 (95% CI 0.52–2.49) which was similar to those with Asian ancestry 1.57 (95% CI 1.15–1.98). NMOSD prevalence in Australian Aboriginal and Torres Strait Islander populations was 0.38 (95% CI 0.00–0.80) per 100,000.
Conclusion
The prevalence of NMOSD in the Māori population is similar to South East Asian countries, reflecting their historical origins. The prevalence of MS in this group is intermediate between those with South East Asian and European ancestry living in New Zealand. Both NMOSD and particularly MS appear to be uncommon in the Indigenous populations of Australia.
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