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  1. 1. NEUROLOGICAL CONDITIONS UPDATE FOR FEBRUARY 2009 Ballard, C. et al. The dementia antipsychotic withdrawal trial (DART-AD) : long-term follow-up of a randomized placebo-controlled trial. The Lancet : Neurology. 2009, Feb : 8(2) : 151-157. Abstract : Data from 12-week placebo-controlled trials have led to mounting concerns about increased mortality in patients with Alzheimer's disease (AD) who are prescribed antipsychotics; however, there are no mortality data from long-term placebo-controlled trials. We aimed to assess whether continued treatment with antipsychotics in people with AD is associated with an increased risk of mortality. Methods : Between October, 2001, and December, 2004, patients with AD who resided in care facilities in the UK were enrolled into a randomised, placebo-controlled, parallel, two-group treatment discontinuation trial. Participants were randomly assigned to continue with their antipsychotic treatment (thioridazine, chlorpromazine, haloperidol, trifluoperazine, or risperidone) for 12 months or to switch their medication to an oral placebo. The primary outcome was mortality at 12 months. An additional follow-up telephone assessment was done to establish whether each participant was still alive 24 months after the enrolment of the last participant (range 24—54 months). Causes of death were obtained from death certificates. Analysis was by intention to treat (ITT) and modified intention to treat (mITT). This trial is registered with the Cochrane Central Registry of Controlled Trials/National Research Register, number ISRCTN33368770. Findings : 165 patients were randomised (83 to continue antipsychotic treatment and 82 to placebo), of whom 128 (78%) started treatment (64 continued with their treatment and 64 received placebo). There was a reduction in survival in the patients who continued to receive antipsychotics compared with those who received placebo. Cumulative probability of survival during the 12 months was 70% (95% CI 58—80%) in the continue treatment group versus 77% (64—85%) in the placebo group for the mITT population. Kaplan— Meier estimates of mortality for the whole study period showed a significantly increased risk of mortality for patients who were allocated to continue antipsychotic treatment compared with those allocated to placebo (mITT log rank p=0·03; ITT p=0·02). The hazard ratio for the mITT group was 0·58 (95% CI 0·35 to 0·95) and 0·58 (0·36 to 0·92) for the ITT population. The more pronounced differences between groups during periods of follow up longer than 12 months were evident at specific timepoints (24-month survival 46% vs 71%; 36-month survival 30% vs 59%). Interpretation : There is an increased long-term risk of mortality in patients with AD who are prescribed antipsychotic medication; these results further highlight the need to seek less harmful alternatives for the long-term treatment of neuropsychiatric symptoms in these patients. Bernhardt, J. et al. Very early versus delayed mobilisation after stroke. Cochrane Database of Systematic Reviews, 2009. Issue no.1. Abstract : Very early mobilisation is performed in some stroke units and recommended in acute stroke clinical guidelines. It is unclear whether very early mobilisation independently improves outcome after stroke. Objectives : To determine the benefits and harms of very early mobilisation (commenced within 48 hours of stroke) compared with conventional care. Search strategy :We searched the Cochrane Stroke Group Trials Register (last searched April 2008). In addition, we searched 25 databases including the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2007), MEDLINE (1950 to August 2007), EMBASE (1980 to September 2007), CINAHL (1982 to December 2006), and AMED (1985 to January 2007). We also searched relevant ongoing trials and research registers (searched January 2007) and the Chinese medical database Wanfangdata (searched March 2007), handsearched journals, searched reference lists and Neurological Conditions Update for February 2009 Library Service, Powys Teaching Local Health Board
  2. 2. contacted researchers in the field. Selection criteria : Unconfounded RCTs of acute stroke patients, comparing an intervention group that started out of bed mobilisation within 48 hours of stroke and aimed to reduce time to first mobilisation and/or increase the amount or frequency (or both) of mobilisation, with conventional care. Data collection and analysis :One review author eliminated obviously irrelevant records; two review authors independently applied selection criteria to remaining studies. The primary outcome was death or poor outcome (dependency or institutionalisation) at the end of scheduled follow up. Secondary outcomes included mortality, dependency, institutionalisation, activities of daily living (ADLs), quality of life, time to walking, adverse events (e.g. deep vein thrombosis) and patient mood. Main results : One study, involving 71 participants, was included. In this study the experimental group had earlier and more frequent mobilisation than the control group (median 18.1 hours post stroke for experimental group versus 30.8 hours control; 167 minutes of mobilisation (interquartile range (IQR) 62 to 305) during admission for experimental group versus 69 (IQR 31 to 115) minutes control). Fewer patients who received early and frequent mobilisation were dead or disabled at three months, but this was not statistically significant and the confidence intervals were wide (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.25 to 1.79, P = 0.42). No significant difference on any secondary outcomes of interest were found. Authors' conclusions : We found insufficient evidence to support or refute the efficacy of routine very early mobilisation after stroke, compared with conventional care. More research is required to determine the benefits and harms of very early mobilisation after stroke. (Copyright Cochrane Library, John Wiley & Sons, Inc., 2009). Bigal, M.E.; Lipton, R.B. Excessive acute migraine medication use and migraine progression. Neurology. 2008, Nov : 71(22) : 1821-8. Long considered a chronic disorder with a stable course, recent research demonstrates that, in a subgroup, migraine progresses to chronic migraine. Among the risk factors for migraine progression, acute symptomatic medication overuse (SMO) is regarded as one of the most important. Though SMO and chronic migraine are associated, several questions remain unanswered. First, the causal path is controversial (SMO as a cause or consequence). Second, it is unclear if specific classes of medication, as well as critical doses of exposures, are necessary. Herein we review this topic in the light of recent conducted research. Although several caveats exist and the data should be taken with caution, important findings are as follows: 1) Opiates are associated with migraine progression; critical dose of exposure is around 8 days per month, and the effect is more pronounced in men. 2) Barbiturates are also associated with migraine progression. Critical dose of exposure is around 5 days per month and the effect is more pronounced in women. 3) Triptans induced migraine progression in those with high frequency of migraine at baseline (10-14 days per month), but not overall. 4) Anti-inflammatory medications were protective in those with <10 days of headache at baseline, and, as triptans, induced migraine progression in those with high frequency of headaches. Accordingly, specific classes of medications are associated with migraine progression, and high frequency of headaches seems to be a risk factor for chronic migraine regardless of medication exposure. Loscher, W. et al. The clinical impact of pharmacogenetics on the treatment of epilepsy. Epilepsia. 2009, Jan : 50(1) : 1-23. Abstract : Drug treatment of epilepsy is characterized by unpredictability of efficacy, adverse drug reactions, and optimal doses in individual patients, which, at least in part, is a consequence of genetic variation. Since genetic variability in drug metabolism was reported to affect the treatment with phenytoin more than 25 years ago, the ultimate goal of pharmacogenetics is to Neurological Conditions Update for February 2009 Library Service, Powys Teaching Local Health Board
  3. 3. use the genetic makeup of an individual to predict drug response and efficacy, as well as potential adverse drug events. However, determining the practical relevance of pharmacogenetic variants remains difficult, in part because of problems with study design and replication. This article reviews the published work with particular emphasis on pharmacogenetic alterations that may affect efficacy, tolerability, and safety of antiepileptic drugs (AEDs), including variation in genes encoding drug target (SCN1A), drug transport (ABCB1), drug metabolizing (CYP2C9, CYP2C19), and human leucocyte antigen (HLA) proteins. Although the current studies associating particular genes and their variants with seizure control or adverse events have inherent weaknesses and have not provided unifying conclusions, several results, for example that Asian patients with a particular HLA allele, HLA-B*1502, are at a higher risk for Stevens-Johnson syndrome when using carbamazepine, are helpful to increase our knowledge how genetic variation affects the treatment of epilepsy. Although genetic testing raises ethical and social issues, a better understanding of the genetic influences on epilepsy outcome is key to developing the much needed new therapeutic strategies for individuals with epilepsy. Mohan, M. Rivastigmine for dementia in people with Down syndrome. Cochrane Database of Systematic Reviews, 2009. Issue no.1. Abstract : Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome (DS). Acetylcholine is a chemical found in the brain that has an important role in memory, attention, reason and language. Rivastigmine is a “pseudo-irreversible” inhibitor of acetylcholinesterase, which is thought to maintain levels of acetylcholine. Rivastigmine can improve cognitive function and slow the decline of AD in the general population over time. It is important to note that people with DS tend to present with AD at a much younger age than the normal population as well as having subtle differences in physiology (e.g. metabolism and heart rate) and may therefore have different requirements from the general population. Objectives : To determine the effectiveness and safety of rivastigmine for people with DS who develop AD. Search strategy : CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI and the NRR were searched up to October 2008. We contacted the manufacturers of rivastigmine as well as experts in the field, to ask about reports of unpublished or ongoing trials. Selection criteria : Randomised controlled trials of participants with DS and AD in which treatment with rivastigmine was administered compared with a placebo group. Data collection and analysis :No study was identified which met inclusion criteria for this review. Main results :No study was identified which met inclusion criteria for this review. Authors' conclusions :As there are no included trials, recommendations cannot be made about rivastigmine for AD in DS. Well-designed, adequately powered studies are required. (Copyright Cochrane Library, John Wiley & Sons, Inc., 2009). If you would like copies of any of the items listed above, please contact the Library Service at Bronllys Hospital or complete one of our request forms and send to the Library at Bronllys. Please note we are only able to supply material to eligible members of the Library Service – please see the Library’s website for details of who may join Powys Teaching LHB’s Library Service. Neurological Conditions Update for February 2009 Library Service, Powys Teaching Local Health Board
  4. 4. Neurological Conditions Update for February 2009 Library Service, Powys Teaching Local Health Board