Author Report for: Wilkinson DNo contact information in database for Wilkinson D
Bethell G, Wilkinson D, Fawkner-Corbett D, Mesa A, Shukla R, Edgar D, Kenny S Ref: J Pediatr Surg, 51:1581, 2016 : PubMed ESTHER: Bethell_2016_J.Pediatr.Surg_51_1581 PubMedSearch: Bethell 2016 J.Pediatr.Surg 51 1581 PubMedID: 27417341 Abstract BACKGROUND/PURPOSE: Despite current treatments patients with Hirschsprung's disease (HSCR) suffer significant long-term morbidity. Therefore, there is increasing interest in adjunctive therapies, such as using enteric nervous system stem cells (ENSSC), isolated from typical aganglionic bowel. The source of these cells is unclear however it is hypothesized that they are present in the thickened nerve trunks in aganglionic short and long segment HSCR gut. These cells should therefore be absent in total colonic and pan intestinal HSCR where these thickened fibers are absent. Title: Memantine in patients with Alzheimer's disease receiving donepezil: new analyses of efficacy and safety for combination therapy Atri A, Molinuevo JL, Lemming O, Wirth Y, Pulte I, Wilkinson D Ref: Alzheimers Res Ther, 5:6, 2013 : PubMed ESTHER: Atri_2013_Alzheimers.Res.Ther_5_6 PubMedSearch: Atri 2013 Alzheimers.Res.Ther 5 6 PubMedID: 23336974 Abstract ABSTRACT: INTRODUCTION: Memantine and cholinesterase inhibitors potentially offer additional benefits in Alzheimer's disease (AD) when used together. This study assessed the efficacy and safety of combination treatment with memantine added to stable donepezil in patients with moderate to severe AD, and a subset with moderate AD. Title: Memantine and brain atrophy in Alzheimer's disease: a 1-year randomized controlled trial Wilkinson D, Fox NC, Barkhof F, Phul R, Lemming O, Scheltens P Ref: J Alzheimers Dis, 29:459, 2012 : PubMed ESTHER: Wilkinson_2012_J.Alzheimers.Dis_29_459 PubMedSearch: Wilkinson 2012 J.Alzheimers.Dis 29 459 PubMedID: 22269160 Abstract The primary objective of this study was to evaluate the rate of total brain atrophy (TBA) with serial magnetic resonance imaging (MRI), using the Brain Boundary Shift Integral (BBSI), in patients with probable Alzheimer's disease (AD) over the course of 52 weeks of treatment with memantine or placebo. This was a multi-national, randomized, double-blind, placebo-controlled, fixed-dose 1-year study. Patients were randomized (1 : 1) to treatment with placebo or memantine. Patients randomized to memantine were up-titrated to the target dose of 20 mg/day over 4 weeks. MRI scans were collected at screening and at Weeks 4, 42, and 52. Secondary efficacy assessments included several cognitive and behavioral scales. 518 patients were screened, 278 patients were randomized, and 217 patients completed the study. In the primary efficacy analysis, the differences in TBA rates between memantine (15.2 mL/year) and placebo (15.3 mL/year) were not statistically significant (-0.04 mL/year [(95% CI: -2.60, 2.52), p = 0.98]). There was a statistically significant correlation between change in TBA and change in most cognitive and behavioral scale scores. Patients who were not treated with acetyl cholinesterase inhibitors (AChEIs) showed a significantly lower TBA rate than patients treated with AChEIs. Memantine had a placebo-level incidence of adverse events. There were no statistically significant differences between memantine and placebo in total brain or hippocampal atrophy rates in patients with probable AD treated for 1 year. The biological relevance of cerebral atrophy was supported by a significant correlation between rate of atrophy and decline in cognitive and behavioral outcomes. Title: A review of the effects of memantine on clinical progression in Alzheimer's disease Wilkinson D Ref: Int J Geriatr Psychiatry, 27:769, 2012 : PubMed ESTHER: Wilkinson_2012_Int.J.Geriatr.Psychiatry_27_769 PubMedSearch: Wilkinson 2012 Int.J.Geriatr.Psychiatry 27 769 PubMedID: 21964871 Abstract BACKGROUND: As Alzheimer's disease (AD) progresses, patients become increasingly dependent on others, placing a substantial impact on the daily lives of patients and caregivers. A treatment that slows clinical progression is a realistic and meaningful therapeutic goal for patients and caregivers. If given early, such a treatment would be expected to maximise any potential benefit. Memantine has shown clinical benefits in the key domains of AD, both as monotherapy and in combination with a cholinesterase inhibitor (ChEI). METHODS: Memantine now has a considerable database of published studies and is associated with benefits in aspects of behaviour, cognition and communication, and on clinical progression. The results of these clinical studies are reviewed. RESULTS: Short-term clinical studies (<=28 weeks) have shown that memantine reduces clinical worsening and has also demonstrated positive effects in aspects of cognition--language, memory, praxis, functional communication--and in activities of daily living. Furthermore, memantine has been shown to reduce the rate of emergence of troublesome behaviour in patients with AD who were asymptomatic at baseline. Long-term follow-up studies (>1 year) have shown that the benefits of memantine are sustained and increase over time, and that memantine can delay nursing home placement in patients with AD. CONCLUSIONS: These findings provide evidence for the benefits of memantine, either alone or in combination with a ChEI, in slowing clinical progression in AD, and indicate that early treatment initiation may maximise clinical success. The benefits of memantine increase over time, allowing patients to remain independent for longer, alleviating caregiver burden and delaying institutionalisation. Title: Modelling long-term effects of IGRs on honey bee colonies Thompson HM, Wilkins S, Battersby AH, Waite RJ, Wilkinson D Ref: Pest Manag Sci, 63:1081, 2007 : PubMed ESTHER: Thompson_2007_Pest.Manag.Sci_63_1081 PubMedSearch: Thompson 2007 Pest.Manag.Sci 63 1081 PubMedID: 17879960 Abstract Systems have been developed to monitor the direct effects of insect growth regulator (IGR) pesticide exposure on honey bee development, but there has been little work on the longer-term impact of exposure on the colony. A honey bee population model provided the opportunity to investigate the effects of short-term mortality of brood and of sublethal changes in behaviour of the surviving adults on honey bee populations. The model showed that brood mortality alone has limited effect on colony size. There were two mechanisms that could have greater influence on productivity. Precocious foraging in affected adult bees, and hence early loss of brood-rearing (nurse) capabilities, had a much larger effect than expected. Increasing mortality rates by 30% to simulate sublethal effects on lifespan, rather than reduced brood-rearing capability, gave a significantly smaller effect. In order to simulate an effect with the 'shortened lifespan' mechanism as large as that with the 'premature ageing' mechanism, the mortality rate of affected adults had to be increased by 500%. A significant finding from the model is that application of IGRs in spring and early summer could have substantial effects on colony size and viability. Sublethal effects such as precocious foraging can have worse effects than massive brood mortality, as it severely reduces the ability to rear the next generation of nurse bees. Title: Clinical practice with anti-dementia drugs: a consensus statement from British Association for Psychopharmacology Burns A, O'Brien J, Auriacombe S, Ballard C, Broich K, Bullock R, Feldman H, Ford G, Knapp M and Wilkinson D <13 more author(s)> Burns A, O'Brien J, Auriacombe S, Ballard C, Broich K, Bullock R, Feldman H, Ford G, Knapp M, McCaddon A, Iliffe S, Jacova C, Jones R, Lennon S, McKeith I, Orgogozo JM, Purandare N, Richardson M, Ritchie C, Thomas A, Warner J, Wilcock G, Wilkinson D (- 13) Ref: J Psychopharmacol, 20:732, 2006 : PubMed ESTHER: Burns_2006_J.Psychopharmacol_20_732 PubMedSearch: Burns 2006 J.Psychopharmacol 20 732 PubMedID: 17060346 Abstract The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review the evidence on the drug treatment for dementia. The level of evidence (types) was rated using a standard system: Types 1a and 1b (evidence from meta-analysis of randomised controlled trials or at least one controlled trial respectively); types 2a and 2b (one well-designed study or one other type of quasi experimental study respectively); type 3 (non-experimental descriptive studies); and type 4 (expert opinion). There is type 1a evidence for cholinesterase inhibitors (donepezil, rivastigmine and galantamine) for mild to moderate Alzheimer's disease; memantine for moderate to severe Alzheimer's disease; and for the use of bright light therapy and aromatherapy. There is type 1a evidence of no effect of anti inflammatory drugs or statins. There is conflicting evidence regarding oestrogens, with type 2a evidence of a protective effect of oestrogens but 1b evidence of a harmful effect. Type 1a evidence for any effect of B12 and folate will be forthcoming when current trials report. There is type 1b evidence for gingko biloba in producing a modest benefit of cognitive function; cholinesterase inhibitors for the treatment of people with Lewy body disease (particularly neuropsychiatric symptoms); cholinesterase inhibitors and memantine in treatment cognitive impairment associated with vascular dementia; and the effect of metal collating agents (although these should not be prescribed until more data on safety and efficacy are available). There is type 1b evidence to show that neither cholinesterase inhibitors nor vitamin E reduce the risk of developing Alzheimer's disease in people with mild cognitive impairment; and there is no evidence that there is any intervention that can prevent the onset of dementia. There is type 1b evidence for the beneficial effects of adding memantine to cholinesterase inhibitors, and type 2b evidence of positive switching outcomes from one cholinesterase inhibitor to another. There is type 2a evidence for a positive effect of reminiscence therapy, and type 2a evidence that cognitive training does not work. There is type 3 evidence to support the use of psychological interventions in dementia. There is type 2 evidence that a clinical diagnosis of dementia can be made accurately and that brain imaging increases that accuracy. Although the consensus statement dealt largely with medication, the role of dementia care in secondary services (geriatric medicine and old age psychiatry) and primary care, along with health economics, was discussed. There is ample evidence that there are effective treatments for people with dementia, and Alzheimer's disease in particular. Patients, their carers, and clinicians deserve to be optimistic in a field which often attracts therapeutic nihilism. Title: The effects of four insect growth-regulating (IGR) insecticides on honeybee (Apis mellifera L.) colony development, queen rearing and drone sperm production Thompson HM, Wilkins S, Battersby AH, Waite RJ, Wilkinson D Ref: Ecotoxicology, 14:757, 2005 : PubMed ESTHER: Thompson_2005_Ecotoxicology_14_757 PubMedSearch: Thompson 2005 Ecotoxicology 14 757 PubMedID: 16160749 Inhibitor(s) related to this paper: Fenoxycarb Abstract This study assessed the effects of exposure to IGRs on the long-term development of the honeybee colony, viability of queens and sperm production in drones and integrated the data into a honeybee population model. Colonies treated with diflubenzuron resulted in a short-term reduction in the numbers of adult bees and brood. Colonies treated with fenoxycarb declined during the season earlier and started the season slower. The number of queens that successfully mated and laid eggs was affected in the fenoxycarb treatment group but there were no significant differences in the drone sperm counts between the colonies. An existing honeybee population model was modified to include exposure to IGRs. In the model, fenoxycarb reduced the winter size of the colony, with the greatest effects following a June or an August application. Assuming a 'larvae per nurse bee' ratio of 1.5 for brood rearing capability, the reduction in winter size of a colony following a fenoxycarb application was at its worst about 8%. However, even if only those bees reared within 2 weeks of the IGR being applied are subject to premature ageing, this might significantly reduce the size of over-wintering colonies, and increase the chance of the bee population dwindling and dying in late winter or early spring. Title: AD2000: design and conclusions Holmes C, Burns A, Passmore P, Forsyth D, Wilkinson D Ref: Lancet, 364:1213, 2004 : PubMed Title: The safety and tolerability of donepezil in patients with Alzheimer's disease Jackson S, Ham RJ, Wilkinson D Ref: British Journal of Clinical Pharmacology, 58 Suppl 1:1, 2004 : PubMed ESTHER: Jackson_2004_Br.J.Clin.Pharmacol_58 Suppl 1_1 PubMedSearch: Jackson 2004 Br.J.Clin.Pharmacol 58 Suppl 1 1 PubMedID: 15496217 Abstract Cholinesterase (ChE) inhibitors, which prevent the hydrolysis of acetylcholine, have been approved for the symptomatic treatment of Alzheimer's disease (AD) for over a decade. However, the first ChE inhibitors were associated with a high incidence of side-effects and general tolerability concerns, including hepatotoxicity. Side-effects associated with increased cholinergic activity, particularly in the gastrointestinal (GI) system, can prevent patients from achieving effective doses of drug. In addition, the advanced age and frail nature of patients with AD mean that poor tolerability is a serious concern. The potential for drug-drug interactions is also an important consideration, due to the high prevalence of comorbid disease in these patients. Data both from clinical trials and studies in routine clinical practice have shown that donepezil is associated with a low incidence of GI adverse events (AEs) that is comparable with placebo. Donepezil is a potent, selective inhibitor of acetylcholinesterase, and selective inhibition of central as opposed to peripheral ChEs might be expected to reduce the incidence of AEs, thus this may explain the lower incidence of cholinergic AEs observed following treatment with donepezil, compared with nonselective ChE inhibitors. There are no differences in cardiovascular AEs, including bradycardia, between placebo and donepezil groups in the clinical trials published to date, even in a very sick vascular dementia population with high rates of comorbidity and concomitant medication use. Data from single- and multiple-dose studies of donepezil in patients with hepatic impairment and with moderately to severely impaired renal function indicate that donepezil is safe and well tolerated in these groups. Furthermore, both in vitro and clinical studies have shown that donepezil is not associated with drug-drug interactions. The incidence of weight loss is very similar between donepezil- and placebo-treated patients. Although insomnia and other sleep disorders have been reported following administration of donepezil, lengthening the time period before increasing the dose of donepezil from 5 to 10 mg day(-1) or switching to morning dosing can reduce these events to the levels of placebo-treated patients. Over 770 million days of patient use and an extensive publication database demonstrate that donepezil has a good tolerability and safety profile. Title: Long-Term use of rivastigmine in patients with dementia with Lewy bodies: an open-label trial Grace J, Daniel S, Stevens T, Shankar KK, Walker Z, Byrne EJ, Butler S, Wilkinson D, Woolford J and McKeith IG <1 more author(s)> Grace J, Daniel S, Stevens T, Shankar KK, Walker Z, Byrne EJ, Butler S, Wilkinson D, Woolford J, Waite J, McKeith IG (- 1) Ref: Int Psychogeriatr, 13:199, 2001 : PubMed ESTHER: Grace_2001_Int.Psychogeriatr_13_199 PubMedSearch: Grace 2001 Int.Psychogeriatr 13 199 PubMedID: 11495394 Abstract Patients with dementia with Lewy bodies (DLB) have progressive deficits in cognition, parkinsonism, and neuropsychiatric symptoms. Cholinesterase inhibitors have been used to ameliorate cognitive decline and neuropsychiatric symptoms in short-term trials. In this study, patients with DLB were treated with rivastigmine up to 96 weeks. Improvement from baseline was seen in cognitive function as measured by the Mini-Mental State Examination (MMSE), and neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI) over the first 24 weeks of treatment. By 96 weeks, neither the MMSE scores nor the NPI scores were significantly worse than at baseline. Title: Galantamine: a randomized, double-blind, dose comparison in patients with Alzheimer's disease Wilkinson D, Murray J Ref: Int J Geriatr Psychiatry, 16:852, 2001 : PubMed ESTHER: Wilkinson_2001_Int.J.Geriatr.Psychiatry_16_852 PubMedSearch: Wilkinson 2001 Int.J.Geriatr.Psychiatry 16 852 PubMedID: 11571763 Abstract OBJECTIVES To investigate whether Galantamine significantly improves the core symptoms of Alzheimer's disease (AD). BACKGROUND: Galantamine is a reversible, competitive, selective inhibitor of acetylcholinesterase (AChE) that also allosterically modulates nicotinic acetylcholine receptors. This dual mechanism of action provided the rationale for a phase II trial of galantamine in AD. METHOD: A multicentre, randomized, parallel, double-blind, placebo-controlled trial was carried out to evaluate the efficacy and tolerability of galantamine 18, 24 and 36 mg/day administered for 3 months in 285 patients with mild-to-moderate probable AD. The primary outcome measure was the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog); secondary outcome measures were the Clinical Global Impression of Change (CGIC) and the Progressive Deterioration Scale (PDS). RESULTS: Patients treated with galantamine 24 mg/day had a significantly better outcome than placebo on ADAS-cog; the treatment difference was 3 points on the intention-to-treat (ITT) analysis ( p = 0.01) and 4.2 points on per protocol analysis ( p = 0.001). Per protocol analysis showed that galantamine had a significantly better outcome than placebo on PDS ( 24-mg/day dose, p < 0.05) and CGIC (36-mg/day dose, p < 0.05). Galantamine was well tolerated at the lower doses of 18 and 24 mg/day where it produced mild, transient effects typical of cholinomimetic agents. CONCLUSION: This study shows that, relative to placebo, galantamine significantly improves the core symptoms of Alzheimer's disease. Title: Pharmacotherapy of Alzheimer's disease: is there a need to redefine treatment success? Winblad B, Brodaty H, Gauthier S, Morris JC, Orgogozo JM, Rockwood K, Schneider L, Takeda M, Tariot P, Wilkinson D Ref: Int J Geriatr Psychiatry, 16:653, 2001 : PubMed ESTHER: Winblad_2001_Int.J.Geriatr.Psychiatry_16_653 PubMedSearch: Winblad 2001 Int.J.Geriatr.Psychiatry 16 653 PubMedID: 11466744 Abstract The traditional aim of Alzheimer's disease treatment in clinical trials has been to improve cognitive abilities. It has become increasingly clear, however, that other aspects are important in assessing treatment responses. A group of 10 physicians recently gathered to review the current criteria for assessing treatment success in Alzheimer's disease. While cognition has been previously viewed as the primary measure of efficacy, areas such as functional abilities, behaviour, caregiver burden, quality of life and resource utilization all need to be comprehensively assessed to fully evaluate treatment effects in patients with Alzheimer's disease, as well as their impacts on caregivers and society. Postponing or slowing decline in any of these areas may represent an important benefit and should be considered as an outcome measure in clinical trials, clinical practice and decision-making about healthcare budgets. Accepted instruments are available for assessing outcomes in each aspect of Alzheimer's disease, but they need to be selected carefully to provide valid, meaningful data. Some of the most frequently used outcome measures in Alzheimer's disease are reviewed. Using expanded criteria for treatment success and clinically relevant outcome measures, data from currently available studies show that cholinesterase inhibitors produce clinically meaningful long-term benefits in multiple domains in patients with Alzheimer's disease. Title: Rivastigmine in the treatment of dementia with Lewy bodies: preliminary findings from an open trial McKeith IG, Grace JB, Walker Z, Byrne EJ, Wilkinson D, Stevens T, Perry EK Ref: Int J Geriatr Psychiatry, 15:387, 2000 : PubMed ESTHER: McKeith_2000_Int.J.Geriatr.Psychiatry_15_387 PubMedSearch: McKeith 2000 Int.J.Geriatr.Psychiatry 15 387 PubMedID: 10822236 Abstract The objective of this study was to assess the tolerability and efficacy of rivastigmine in a group of patients with probable dementia with Lewy bodies (DLB), using an open label study. Open label treatment was with rivastigmine up to maximum tolerated dose (mean 9.6 mg daily, range 3-12 mg). Eleven patients with DLB, mean age 78.5 years, were treated with this cholinesterase inhibitor. After 12 weeks of treatment, mean Neuropsychiatric Inventory scores fell by 73% for delusions, 63% for apathy, 45% for agitation and 27% for hallucinations. Five of the patients (45%) experienced very significant clinical improvements that had not been achieved with other treatments, including low dose neuroleptics. Medication was well tolerated and parkinsonian symptoms tended to improve. Cholinesterase inhibition may be a safe and effective alternative to neuroleptic treatment in DLB. Such effects may also prove to be applicable to the management of neuropsychiatric symptoms in Parkinson's disease and Alzheimer's disease. Title: The impact of metrifonate therapy on caregivers of patients with Alzheimer's disease: results from the MALT clinical trial. Metrifonate in Alzheimer's Disease Trial Shikiar R, Shakespeare A, Sagnier PP, Wilkinson D, McKeith I, Dartigues JF, Dubois B Ref: J Am Geriatr Soc, 48:268, 2000 : PubMed ESTHER: Shikiar_2000_J.Am.Geriatr.Soc_48_268 PubMedSearch: Shikiar 2000 J.Am.Geriatr.Soc 48 268 PubMedID: 10733052 Abstract OBJECTIVE To assess the impact on burden reported by caregivers of patients with mild to moderate Alzheimer's disease (AD) who were treated with metrifonate during a randomized double blind clinical trial. DESIGN: Randomized clinical trial, with a 2-week screening period and a 26-week double blind, placebo controlled, treatment phase. Caregivers were assessed at baseline, at 12 weeks, and at end of trial. SETTING: Caregivers were interviewed at clinics as part of the assessment of the patients. PARTICIPANTS: Six hundred and three caregivers of AD patients who were enrolled in the MALT trial; 591 (98%) provided data suitable for analysis at baseline, and 546 (91%) provided data allowing for inclusion in the analysis of change scores. MEASUREMENTS: The Caregiver Burden Assessment consisted of the Screen for Caregiver Burden, including both subjective (SCB-subj) and objective (SCB-obj) scores; the cognitive subscale of Poulshock and Deimling (PD); an abridged version of the Relatives Stress Scale (aRSS); assessments of time spent in providing care, including the Caregiver Activity Time Scale (CATS); and demographic and background variables on both the patient and caregiver. RESULTS: Treatment of mild to moderate AD patients with metrifonate for a duration of 26 weeks significantly reduced the psychological burden of care to the caregivers, as measured by the SCB-subj, the PD, and the aRSS. There were no statistically significant differences on the measures assessing the time spent in caregiving, except for the caregiver's subjective impression of the change in time spent providing care during the trial. When comparing individual dose groups, most of the measures of burden showed the largest benefits in burden for the 60/80 mg group, followed by the 40/50 mg group, and then the placebo group. However, there was no statistically significant dose effect. Title: Clinical experience with Donepezil (Aricept) in the UK Wilkinson D Ref: J Neural Transm Suppl, 54:311, 1998 : PubMed ESTHER: Wilkinson_1998_J.Neural.Transm.Suppl_54_311 PubMedSearch: Wilkinson 1998 J.Neural.Transm.Suppl 54 311 PubMedID: 9850940 Abstract Experience of the use of Donepezil (Aricept) in the UK since licensing is discussed. The results of a 30 week double blind parallel group study in the US of Donepezil 5 or 10 mg versus placebo show statistically significant improvements in cognitive and clinical global assessments. Beneficial effects were demonstrated in the absence of significant adverse effects on physical or laboratory values. The guidelines for use adopted in the UK are discussed with the emphasis on identifying non-cognitive behaviours, as significant improvements in these have been found and often have more impact on quality of life than cognitive improvements alone. Title: Advertisements for donepezil. Review of drug in Drug and Therapeutics Bulletin is uninformed Wilkinson D Ref: BMJ, 315:1625, 1997 : PubMed ESTHER: Wilkinson_1997_BMJ_315_1625 PubMedSearch: Wilkinson 1997 BMJ 315 1625 PubMedID: 9437307 Inhibitor(s) related to this paper: Aricept~Donepezil~E2020 | |||||||
|
