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Biomedical subjects

R McShane

Publications and source records attributed to R McShane.

18 recordsLinked to original sources
PubMed2006

Memantine for dementia.

BACKGROUND: Memantine, a low affinity antagonist to glutamate NMDA receptors, may prevent excitatory neurotoxicity in dementia. OBJECTIVES: To determine efficacy and safety of memantine for people with Alzheimer's disease (AD), vascular (VD) and mixed dementia. SEARCH STRATEGY: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 8th February 2006. This register contains references from all major healthcare databases and many ongoing trial databases and is updated regularly. In addition, the search engines Copernic and Google were used to identify unpublished trials through inspection of the websites of licensing bodies like the FDA , EMEA and NICE and of companies' websites (Lundbeck, Merz, Forest, Suntori etc) and clinical trials registries. SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled, randomized trials of memantine in people with dementia. DATA COLLECTION AND ANALYSIS: Data were pooled where possible. Intention-to-treat (ITT) and observed case (OC) analyses are reported. MAIN RESULTS: 1. Moderate to severe AD. Two out of three six month studies show a small beneficial effect of memantine. Pooled data indicate a beneficial effect at six months on cognition (2.97 points on the 100 point SIB, 95% CI 1.68 to 4.26, P < 0.00001), activities of daily living (1.27 points on the 54 point ADCS-ADLsev, 95% CI 0.44 to 2.09, P = 0.003) and behaviour (2.76 points on the 144 point NPI, 95% CI 0.88 to 4.63, P=0.004), supported by clinical impression of change (0.28 points on the 7 point CIBIC+, 95% CI 0.15 to 0.41, P < 0.0001).2. Mild to moderate AD. Pooled data from three unpublished studies indicate a marginal beneficial effect at six months on ITT cognition (0.99 points on the 70 point ADAS-Cog, 95% CI 0.21 to 1.78, P = 0.01) which was barely detectable clinically (0.13 CIBIC+ points, 95% CI 0.01 to 0.25, P = 0.03) but no effect on behaviour, activities of daily living or OC analysis of cognition.3. Mild to moderate vascular dementia. Pooled data from two six month studies indicated a small beneficial effect of memantine on cognition (1.85 ADAS-Cog points, 95% CI 0.88 to 2.83, P = 0.0002), and behaviour (0.84 95% CI 0.06 to 0.91, P = 0.03) but this was not supported by clinical global measures.4. Patients taking memantine were slightly less likely to develop agitation (134/1739, 7.7% versus 175/1873, 9.3% OR 0.78, 95% CI 0.61 to 0.99, P = 0.04). This effect was slightly larger, but still small, in moderate to severe AD (58/506 [12%] vs 88/499 [18%]; OR = 0.6, 95% CI 0.42 to 0.86, P = 0.005). There is no evidence either way about whether it has an effect on agitation which is already present.5. Memantine is well tolerated. AUTHORS' CONCLUSIONS: Memantine has a small beneficial effect at six months in moderate to severe AD. In patients with mild to moderate dementia, the small beneficial effect on cognition was not clinically detectable in those with vascular dementia and was detectable in those with AD. Memantine is well tolerated.

Activities of Daily Living↗
PubMed2006

Clioquinol for the treatment of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) may result in senile plaques being formed outside the brain as accumulation of beta-amyloid (Ass). OBJECTIVES: To evaluate the efficacy of clioquinol for the treatment of cognitive impairment due to Alzheimer's disease. SEARCH STRATEGY: The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched on 20 May 2005 using the terms clioquinol and PBT1. The Register contains records from major health care databases and many ongoing trial databases and is updated regularly. The Internet was searched using the term: clioquinol PBT1 Alzheimer*. SELECTION CRITERIA: Randomised double-blind trials in which treatment with clioquinol was administered to participants with Alzheimer's disease in parallel group comparison with placebo are included. DATA COLLECTION AND ANALYSIS: Two reviewers (RM, LJ) independently assessed the quality of trials according to the Cochrane Collaboration Handbook. The primary outcome measures of interest were cognitive function (as measured by psychometric tests) and global impression. The secondary outcome measures of interest were in the following areas: quality of life, functional performance, effect on carer, safety and adverse effects, and death. MAIN RESULTS: There was one included trial of clioquinol compared with placebo in 36 patients. AUTHORS' CONCLUSIONS: It is not clear from the trial that clioquinol shows any positive clinical result on patients with AD. The two statistically significant positive results were seen for the more severely affected subgroup of patients. This effect was not maintained at the 36 week end-point. The sample size was small. Details of randomisation procedure or blinding were not reported. Further studies are needed to evaluate the potential for clioquinol as a treatment of AD. Trials of longer duration are also required, particularly because information about the side-effects of long-term use of clioquinol is limited.

Aged↗
PubMed2005

Memantine for dementia.

BACKGROUND: Memantine, a low affinity antagonist to glutamate NMDA receptors, may prevent excitatory neurotoxicity in dementia. OBJECTIVES: To determine efficacy and safety of memantine for people with Alzheimer's disease (AD), vascular (VD) and mixed dementia. SEARCH STRATEGY: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 20 May 2005. This register contains references from all major healthcare databases and many ongoing trial databases and is updated regularly. In addition the search engines Copernic and Google were used to identify unpublished trials through inspection of the websites of licensing bodies like the FDA , EMEA and NICE and of companies' websites (Lundbeck, Merz, Forest, Suntori etc) and clinical trials registries. SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled, randomized trials of memantine in people with dementia. DATA COLLECTION AND ANALYSIS: Data were pooled where possible. Intention-to-treat (ITT) and observed case (OC) analyses are reported. MAIN RESULTS: 1. Moderate to severe AD. Two out of three six month studies show a small beneficial effect of memantine. Pooled data indicate a beneficial effect at six months on cognition (4.12 points on the 100 point SIB , 95% CI 2.14 to 5.74, P < 0.00001), activities of daily living (1.27 points on the 54 point ADCS-ADLsev, 95% CI 0.44 to 2.09, P = 0.003) and behaviour (2.76 points on the 144 NPI, 95% CI 0.88 to 4.63, P = 0.004), supported by clinical impression of change (0.28 points on the 7 point CIBIC+, 95% CI 0.15 to 0.41, P < 0.0001).2. Mild to moderate AD. In a single six month trial, memantine had a beneficial effect on ITT analysis of cognition, (1.9 ADAS-Cog points, 95% CI 0.35 to 3.45, P = 0.02) and behaviour (3.50 NPI points 95% CI 0.15 to 6.85, P = 0.04) supported by clinical global impression of change (0.30 CIBIC+ points, 95% CI 0.09 to 0.51, P = 0.005), but no effect on activities of daily living or OC analysis of cognition. The statistical significance of these benefits could be overturned by data from two unpublished studies which are known to show no significant effect. 3. Mild to moderate vascular dementia. In two six month studies, memantine improved cognition (1.85 ADAS-Cog points, 95% CI 0.88 to 2.83, P = 0.0002), and behaviour (0.84 95% CI 0.06 to 0.91, P = 0.03) but this was not supported by clinical global measures.4. Patients taking memantine appeared to be less likely to develop agitation (93/1167 [8%] versus 134/1141 [12%] (Peto odds ratio (OR): 0.65, 95% CI 0.49 to 0.86, P = 0.002). This was consistently seen in moderate to severe dementia. There were no data which suggested an effect on agitation which is already present.5. Memantine is well tolerated. AUTHORS' CONCLUSIONS: Published data suggest a small beneficial effect of memantine at six months in moderate to severe AD. The beneficial effect on cognition in patients with mild to moderate vascular dementia was not detectable on global assessment at six months. Whether memantine has any effect in mild to moderate AD is unknown.

Activities of Daily Living↗
PubMed2005

Memantine for dementia.

BACKGROUND: Memantine, a low affinity antagonist to glutamate NMDA receptors, may prevent excitatory neurotoxicity in dementia. OBJECTIVES: To determine efficacy and safety of memantine for people with Alzheimer's disease (AD), vascular (VD) and mixed dementia. SEARCH STRATEGY: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 28 October 2004. This register contains references from all major healthcare databases and many ongoing trial databases and is updated regularly. In addition the search engines Copernic and Google were used to identify unpublished trials through inspection of the websites of licensing bodies like the FDA , EMEA an Nice and of companies' websites (Lundbeck, Merz, Forest, Suntori etc). SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled, randomized trials of memantine in people with dementia. DATA COLLECTION AND ANALYSIS: Data were pooled where possible. Intention-to-treat (ITT) and observed case (OC) analyses are reported. MAIN RESULTS: 1. Moderate to severe AD. A major study (MD-01) is unpublished. Published data from two six month studies show a small beneficial effect of memantine at six months on cognition (4.12 SIB points, 95% Confidence Interval (CI) 2.14 to 5.74, P < 0.00001), activities of daily living (1.70 ADCS-ADLsev19 points, 95% CI 0.63 to 2.76, p = 0.002) and behaviour (3.64 NPI points, 95% CI 1.38 to 5.90, p = 0.002), supported by clinical impression of change (0.27 CIBIC+ points, 95% CI 0.10 to 0.43, p = 0.002). The unpublished study would need to have found a detrimental effect of memantine to overturn the statistical significance of the benefits apparent in the two published studies. 2. Mild to moderate AD. In a single six month trial, memantine had a beneficial effect on ITT analysis of cognition, (1.9 ADAS-Cog points, 95% CI 0.35 to 3.43, p = 0.02) and behaviour (3.50 NPI points 95% CI 0.15 to 6.85, p = 0.04) supported by clinical global impression of change (0.30 CIBIC+ points, 95% CI 0.09 to 0.51, p = 0.005), but no effect on activities of daily living or OC analysis of cognition. The statistical significance of these benefits could be overturned by data from two unpublished studies which are known to show no significant effect. 3. Mild to moderate vascular dementia. In two six month studies, memantine improved cognition (1.85 ADAS-Cog points, 95% CI 0.88 to 2.83, p = 0.0002), and behaviour (Weighted Mean Difference (WMD) 0.84 95% CI 0.06 to 0.91, p = 0.03) but this was not supported by clinical global measures.4. Patients taking memantine were less likely to develop agitation (Odds Ratio (OR): 0.65, 95% CI 0.48 to 0.89, p = 0.007). The effect on agitation which is already present is unknown.5. Memantine is well tolerated. AUTHORS' CONCLUSIONS: Published data suggest a small beneficial effect of memantine at six months in moderate to severe AD. The beneficial effect on cognition in patients with mild to moderate vascular dementia was not clinically discernible at six months. Whether memantine has any effect in mild to moderate AD is unknown.

Activities of Daily Living↗
PubMed2004

Memantine for dementia.

BACKGROUND: Alzheimer's disease, vascular and mixed dementia are the three commonest forms of dementia affecting older people. There is evidence that the excitatory activity of L-glutamate plays a role in the pathogenesis of Alzheimer's disease and in the damage from an ischaemic stroke. A low affinity antagonist to N-Methyl-D-aspartate (NMDA) type receptors, such as memantine, may prevent excitatory amino acid neurotoxicity without interfering with the physiological actions of glutamate required for memory and learning. OBJECTIVES: To determine the clinical efficacy and safety of memantine for people with Alzheimer's disease, or vascular or mixed dementia. SEARCH STRATEGY: Trials were identified from a search of the Trial-based Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 April 2004 using the terms: memantin*, namenda*, ebixa*, axura*, D-145, DMAA, DRG-0267. All major health care databases and many ongoing trial databases are searched regularly to keep this Register up to date. SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled, randomised and unconfounded trials in which memantine was administered to people with dementia. DATA COLLECTION AND ANALYSIS: Data were extracted, pooled where possible, and weighted mean differences, standardized mean differences or odds ratios were estimated. Intention-to-treat (ITT) and observed cases (OC) analyses are reported, where data were available. MAIN RESULTS: The evidence suggests that memantine has a positive effect on cognition, mood and behaviour and the ability to perform activities of daily living in patients with moderate to severe Alzheimer's disease. The results in patients with mild to moderate vascular dementia, suggest a beneficial effect of 20mg/day of memantine on cognitive function measured at 28 weeks. However, these results are neither supported by an effect on ability to perform activities of daily living nor by an effect on the clinical impression of change. This suggests that, in patients with mild to moderate vascular dementia, the effect on cognitive function is not translated into clinically detectable changes. REVIEWERS' CONCLUSIONS: :Memantine 20 mg/day caused a clinically noticeable reduction in deterioration over 28 weeks in patients with moderate to severe Alzheimer disease. This was supported by less functional and cognitive deterioration. Patients taking memantine were less likely to become agitated. The effect in mild to moderate AD is unknown. Patients with mild to moderate vascular dementia receiving memantine 20 mg/day had less cognitive deterioration at 28 weeks but the effects were not clinically discernible. There is an early beneficial effect on cognition, mood, behaviour and clinical impression for memantine at 6 weeks. The drug is well tolerated in general and the incidence of adverse effects is low.

Activities of Daily Living↗
PubMed2004

Cold perfluorochemical-induced hypothermia protects lung integrity in normal rabbits.

To test the hypothesis that intrapulmonary perfluorochemical (PFC) liquid may induce hypothermia, and to compare the effects of internal (IC), external (EC), and combined cooling techniques (EC + IC), 14 juvenile rabbits were randomized to EC by a cold blanket (4 degrees C, n = 5), IC by intrapulmonary cold PFC liquid lavage (4 degrees C, n = 5), or combined IC with PFC and EC (n = 4). Arterial blood gas, blood pressure, and lung mechanics were monitored, and lung histology was examined by light microscopy. The results showed that cooling rates and the time needed to be cooled down to 30 degrees C were significantly faster in EC and EC + IC than IC (p < 0.05). Blood gas analysis and cardiopulmonary function were within the normal range in all groups. Histological assessment revealed varied atelectasis in all lung regions in EC, whereas PFC-filled lungs (IC and EC + IC) demonstrated more homogenous expansion and no evidence of atelectasis. The results indicate that intrapulmonary PFC may be an effective technique to induce and/or augment hypothermia while supporting gas exchange, lung volume and pulmonary architecture.

Animals↗
PubMed1999

Natural history of behavioural changes and psychiatric symptoms in Alzheimer's disease. A longitudinal study.

BACKGROUND: Alzheimer's disease and other types of dementia are characterised by numerous psychiatric and behavioural changes. Little is known of their natural history. AIMS: To investigate the sequence and pattern of these changes throughout the course of dementia. METHOD: One hundred people, initially living at home with carers, entered a prospective, longitudinal study. At four-monthly intervals, behavioural and psychiatric symptoms were assessed using the Present Behavioural Examination and Mini-Mental State Examination. Follow-up continued for up to nine years (mean 3.3 years; s.d. 2.4). Patterns of onset and disappearance of these symptoms, their sequence and association with time of death and cognitive decline were analysed. Autopsy confirmed a diagnosis of pure Alzheimer's disease in 48 subjects. Data for this subgroup are presented. RESULTS: Some changes tend to occur earlier than others but changes can occur at almost any time in the course of dementia. CONCLUSIONS: The natural history of behaviour changes in Alzheimer's disease shows great individual variation although some changes tend to follow a recognisable sequence.

Aged↗
PubMed1998

The feasibility of electronic tracking devices in dementia: a telephone survey and case series.

BACKGROUND: Patients with dementia who go out unaccompanied are at risk of accidents or getting lost. It is not known whether they could benefit from electronic tracking devices or whether such devices are practically feasible. METHOD: The likely demand for an electronic tracking device was assessed by means of a telephone survey of a convenience sample of 99 carers. The practical feasibility of a tracking system was assessed in 24 patients with dementia. RESULTS: The telephone survey suggested that 20% of patients were at continuing risk of traffic accidents and 45% were at continuing risk of getting lost. About 7% could have benefited from using the device at the time of survey and a further 11% could have benefited at an earlier point in their illness. In the feasibility study, only nine patients consistently used the device. In two patients, it was successfully used in a search. One patient was injured by a passing vehicle when he had got lost out of range of the device. A major barrier to using the device was recognizing the risk of getting lost before it happened. CONCLUSION: Significant numbers of patients are at risk. Electronic tracking devices may occasionally be useful in carefully selected cases.

Accidents, Traffic↗
PubMed1998

Psychiatric symptoms in patients with dementia predict the later development of behavioural abnormalities.

BACKGROUND: Cross-sectional studies of non-cognitive symptoms in dementia show that patients with psychotic symptoms tend to have more disturbed behaviour. However, it is not known whether individuals who experience psychiatric symptoms early in dementia are more prone to develop behavioural problems later in the illness. METHOD: The behaviour of 86 community-dwelling subjects with dementia was intensively studied for 4 years or until death, using an informant interview which was administered every 4 months on a median of eight occasions. The extent to which psychiatric symptoms, age, sex and cognitive function predicted clinically significant physical aggression or motor hyperactivity was assessed. RESULTS: Physical aggression was predicted by sad appearance and motor hyperactivity was predicted by persecutory ideas. These associations were robust, remaining significant over 2, 3 and 4 years of follow-up and were independent of cognitive function, age, sex and duration of illness. CONCLUSIONS: There may be two distinct longitudinal syndromes of non-cognitive symptoms in dementia. This suggests that important aberrant behaviours in late dementia may share pathophysiological mechanisms with psychiatric symptoms in early dementia.

Aged↗
PubMed1998

Getting lost in dementia: a longitudinal study of a behavioral symptom.

The occurrence of episodes of getting lost was examined in 104 subjects with dementia who were assessed every 4 months over 5 years. All subjects were initially living at home with a caregiver who could give good information. Forty-three subjects needed to be brought back home at least once. Five subjects repeatedly got lost. Forty-six subjects were kept behind locked doors at some point. Subjects who got lost were more likely to become permanently resident in institutions (odds ratio = 7.3; 95% confidence interval: 3.0 to 17.8). Patients who performed better on a behavioral test of topographical memory were less likely to get lost over the subsequent 5 years (negative predictive value: 90%). The risk of patients with dementia getting lost is substantial and requires frequent intervention by caregivers. This risk is a major reason for institutionalization. A simple test may help in assessing the risk of getting lost in patients with dementia.

Aged↗
PubMed1997

Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up.

OBJECTIVE: To investigate the contribution of neuroleptic drugs to cognitive decline in dementia. DESIGN: Two year prospective, longitudinal study consisting of interviews every four months, with necropsy follow up. SETTING: Community settings in Oxfordshire. SUBJECTS: 71 subjects with dementia, initially living at home with informant. MAIN OUTCOME MEASURES: Cognitive function (score from expanded minimental state examination); behavioural problems (physical aggression, hallucinations, persecutory ideas, and disturbance of diurnal rhythm); and postmortem neuropathological assessment (cortical Lewy body pathology). RESULTS: The mean (SE) decline in cognitive score in the 16 patients who took neuroleptics was twice that in the patients who did not (20.7 (2.9) v 9.3 (1.3), P = 0.002). An increased rate of decline was also associated with aggression, disturbed diurnal rhythm, and persecutory ideas. However, only use of neuroleptics and severity of persecutory ideas were independently associated with more rapid cognitive decline when all other variables were adjusted for. The start of neuroleptic treatment coincided with more rapid cognitive decline: median rate of decline was 5 (interquartile range 8.5) points per year before treatment and 11 (12) points per year after treatment (P = 0.02). Cortical Lewy body pathology did not account for association between neuroleptic use and more rapid decline. CONCLUSIONS: Neuroleptic drugs that are sometimes used to treat behavioural complications of dementia may worsen already poor cognitive function. Randomised controlled trials are needed to confirm a causal relation.

Aged↗
PubMed1997

Behaviour changes in dementia. 2: Are there behavioural syndromes?

OBJECTIVE: To establish whether robust behavioural 'syndromes' can be identified from among the widely heterogeneous behavioural changes which occur in dementia. DESIGN: Longitudinal, prospective study with follow-up at 4 and 8 months. SETTING: Community settings in Oxfordshire, UK. PARTICIPANTS: 97 elderly people with a diagnosis of Alzheimer's disease or vascular dementia (in many cases confirmed by postmortem examination) and who were living at home with a carer. MEASURES: Each subject's behaviour was assessed in detail at each interview using the Present Behavioural Examination to assess subject's behaviour over the preceding 4 weeks. Seventeen key behaviour items which were both common and clinically important were selected for further analysis. RESULTS: Three syndromes were identified: (a) overactivity (walking more, walking aimlessly, trailing the carer or checking where the carer was); (b) aggressive behaviour (physical aggression, aggressive resistance, verbal aggression); (c) psychosis (anxiety, persecutory ideas and hallucinations). The same syndromes were found using data collected at three different time points and by using a variety of statistical techniques, confirming their robustness. CONCLUSIONS: Overactivity, aggressive behaviour and psychosis form three distinct behavioural syndromes in dementia.

Aged↗
PubMed1995

Prospective study of relations between cortical Lewy bodies, poor eyesight, and hallucinations in Alzheimer's disease.

The presence of hallucinations is included in some, but not all, of the sets of clinical diagnostic criteria that have been proposed for dementia associated with cortical Lewy bodies. These criteria were developed from retrospective casenote analyses. This prospective, longitudinal study suggests that, in patients with Alzheimer's disease, cortical Lewy bodies are associated with more persistent and severe hallucinations, independently of any association with severity of cognitive decline. Poor eyesight contributes to the severity but not the persistence of the hallucinations.

Aged↗
PubMed1990

Use of Vicryl (polyglactin-910) mesh implant for correcting enophthalmos and hypo-ophthalmos. A study of 16 patients.

Vicryl mesh (polyglactin-910) implants were used to reconstruct the orbital floor to correct enophthalmos or hypo-ophthalmos (globe ptosis) in 16 patients. The main advantages of Vicryl mesh over other alloplastic implants is that (a) it is absorbed by host tissue, and, once absorbed, it will not cause long-term complications; (b) it is layered and is cut from folded sheets into the appropriate size, shape, and thickness for the treatment of enophthalmos or hypo-ophthalmos; and (c) it is soft and pliable and, therefore, is unlikely to erode orbital structures. We followed all patients for a minimum period of 6 months after surgery and observed no significant adverse reactions to the mesh; 15 of the patients had good surgical results with a mean improvement of 1.4 mm in enophthalmos and 0.6 mm in hypo-ophthalmos. After surgery, one patient with combined medial wall and floor fractures developed enophthalmos that was 2 mm more severe than the degree of preoperative enophthalmos. Vicryl mesh should be considered an alternative to both nonautogenous implants and autogenous grafts in orbital floor fracture repair especially for correction of mild and possibly moderate degrees of enophthalmos and hypo-ophthalmos.

Adolescent↗