Betsi Cadwaladr University Health Board

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Betsi Cadwaladr University Health Board

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Hindle J.V.,Bangor University | Hindle J.V.,Betsi Cadwaladr University Health Board | Petrelli A.,University of Vechta | Petrelli A.,University of Cologne | And 3 more authors.
Movement Disorders | Year: 2013

Cognitive decline and dementia are frequent in patients with Parkinson's disease (PD). The evidence for nonpharmacological therapies in Alzheimer's disease and other dementias has been studied systematically, but the evidence is unclear for their efficacy in cognition and dementia in PD. An international collaboration produced a comprehensive, systematic review of the effectiveness and of nonpharmacological and noninvasive therapies in cognitively intact, cognitively impaired, and PD dementia groups. The interventions included cognitive rehabilitation, physical rehabilitation, exercise, and brain stimulation techniques but excluded invasive treatments, such as surgery and deep brain stimulation. The potential biases and evidence levels for controlled trials (CTs) were analyzed based on Cochrane and National Institute for Health and Clinical Excellence criteria. After exclusions, 18 studies were reviewed, including 5 studies of cognitive training, 4 of exercise and physical therapies, 4 of combined cognitive and physical interventions, and 5 of brain stimulation techniques. The methodology, study populations, interventions, outcomes, control groups, analyses, results, limitations, biases, and evidence levels of all reviewed studies were described. There were 9 CTs, including 6 randomized CTs (RCTs). Although 5 trials showed positive results, only 1 study of cognitive training achieved evidence grading of 1+ with a low risk of bias. There were no studies on PD dementia. Current research on nonpharmacological therapies for cognitive dysfunction and dementia in PD is very limited in quantity and quality. There is an urgent need for rigorous RCTs of nonpharmacological treatments for cognitive impairment and dementia in PD. © 2013 Movement Disorder Society.

Al-Rawi M.A.,Betsi Cadwaladr University Health Board | Jiang W.G.,University of Cardiff
Frontiers in Bioscience | Year: 2011

Lymphangiogenesis remains a fascinating biological process that plays a crucial role in both normal tissue development and several lymphatic diseases. The last few years have witnessed a rapid progression in understanding the development and regulation of the lymphatic system which provided insight on several pathological processes including cancer lymphatic metastasis. Lymphatic vasculature serves as a major route for tumour metastasis. The dissemination of malignant cells to the regional lymph nodes is an early step in the progression of many solid tumours and is an important determinant of staging and prognosis. Lymphangiogenesis is thought to play a pivotal role for cancer cells to metastasise to the regional lymph nodes. Several human solid tumours are now considered to be lymphangiogenic i.e. they have the ability to induce their own lymphatic vessels to establish metastasis. Hence, targeting lymphangiogenesis by developing anti-lymphangiogenic agents might constitute a novel way to prevent lymphatic progression in some tumours. Here, we have reviewed the development of the lymphatic system, the regulation of lymphangiogenesis and explored its relation to several human cancers.

Hassanein M.,Betsi Cadwaladr University Health Board | Abdallah K.,Alexandria University | Schweizer A.,Novartis
Vascular Health and Risk Management | Year: 2014

Background: Several observational studies were conducted with vildagliptin in patients with type 2 diabetes mellitus (T2DM) fasting during Ramadan, showing significantly lower incidences of hypoglycemia with vildagliptin versus sulfonylureas, including gliclazide. It was of interest to complement the existing real-life evidence with data from a randomized, double-blind, clinical trial. Clinical Trials Identifier: NCT01758380. Methods: This multiregional, double-blind study randomized 557 patients with T2DM (mean glycated hemoglobin [HbA1c], 6.9%), previously treated with metformin and any sulfonylurea to receive either vildagliptin (50 mg twice daily) or gliclazide plus metformin. The study included four office visits (three pre-Ramadan) and multiple telephone contacts, as well as Ramadan-focused advice. Hypoglycemic events were assessed during Ramadan; HbA1c and weight were analyzed before and after Ramadan. Results: The proportion of patients reporting confirmed (<3.9 mmol/L and/or severe) hypoglycemic events during Ramadan was 3.0% with vildagliptin and 7.0% with gliclazide (P=0.039; one-sided test), and this was 6.0% and 8.7%, respectively, for any hypoglycemic events (P=0.173). The adjusted mean change pre- to post-Ramadan in HbA1c was 0.05%±0.04% with vildagliptin and -0.03%±0.04% with gliclazide, from baselines of 6.84% and 6.79%, respectively (P=0.165). In both groups, the adjusted mean decrease in weight was -1.1±0.2 kg (P=0.987). Overall safety was similar between the treatments. Conclusion: In line with the results from previous observational studies, vildagliptin was shown in this interventional study to be an effective, safe, and well-tolerated treatment in patients with T2DM fasting during Ramadan, with a consistently low incidence of hypoglycemia across studies, accompanied by good glycemic and weight control. In contrast, gliclazide showed a lower incidence of hypoglycemia in the present interventional than the previous observational studies. This is suggested to be linked to the specific circumstances of this study, including frequent patient-physician contacts, Ramadan-focused advice, a recent switch in treatment, and very well-controlled patients, which is different from what is often seen in real life. © 2014 Hassanein et al.

Stutchfield P.R.,Betsi Cadwaladr University Health Board
Archives of disease in childhood. Fetal and neonatal edition | Year: 2013

To determine whether antenatal betamethasone prior to elective term caesarean section (CS) affects long term behavioural, cognitive or developmental outcome, and whether the risk of asthma or atopic disease is reduced. A questionnaire based follow-up of a multicentre randomised controlled trial (Antenatal Steroids for Term Elective Caesarean Section, BMJ 2005). Four UK study centres from the original trial. 862 participants from the four largest recruiting centres, 92% of the original study. 824 (96%) were traced and 799 (93%) were successfully contacted. Fifty-one percent (407/799) completed and returned the questionnaire. The children were aged 8-15 years (median 12.2 years, 52% girls). 386 gave consent to contact schools with 352 (91%) reports received. Questionnaires including a strengths and difficulties questionnaire, International Study of Asthma and Allergies in Childhood, general health and school performance. There were no significant differences between children whose mothers received betamethasone and controls for the mean total strengths and difficulties questionnaire scores and subscores for hyperactivity, emotional symptoms, prosocial behaviour, conduct or peer problems. 25 (12%) children whose mothers received betamethasone had reported learning difficulties compared with 27 (14%) control children. The proportion of children who achieved standard assessment tests KS2 exams level 4 or above for mathematics, English or science was similar as were the rates of ever reported wheeze (30% vs 30%), asthma (24% vs 21%), eczema (34% vs 37%) and hay fever (25% vs 27%). Antenatal betamethasone did not result in any adverse outcomes or reduction in asthma or atopy. It should be considered for elective CS at 37-38 weeks of gestation. : Original trial was preregistration, the trial publication is BMJ. 2005 Sep 24;331(7518):662.

Hindle J.V.,Bangor University | Hindle J.V.,Betsi Cadwaladr University Health Board
Journal of Neural Transmission | Year: 2013

Parkinson's disease (PD) has been described as an age-related disease. Ageing significantly increases the risk of psychosis and dementia. Older patients often have a complex mixture of delirium, psychosis, dementia, gait and balance problems and other comorbidities which can cause significant management problems. There are concerns about the safety and tolerability of the treatments for psychosis and dementia. Delirium is common in older Parkinson's patients and must be assessed and managed carefully. The aetiology of psychosis in Parkinson's is complex and often associated with the development of cognitive impairment. Initial adjustments of Parkinson's drugs should be considered if symptoms are intrusive. Where drug therapy is required, evidence suggests that quetiapine may be a safe initial option. There is no contraindication to the use of clozapine in older patients, with the required blood monitoring. Dementia is almost inevitable with very advanced disease and increasing age, and is associated with a marked cholinergic deficit in the brain. Cholinesterase inhibitors may be more effective in PD than in Alzheimer's disease and appear relatively safe with appropriate monitoring of the pulse. There is much less evidence for the use of memantine. There is no current evidence for the use of specific non-pharmacological therapies in the management of psychosis or dementia in PD. Due to the associated gait and balance problems, older Parkinson's patients benefit from comprehensive multi-disciplinary assessment. © 2013 Springer-Verlag Wien.

Hindle J.V.,Bangor University | Hindle J.V.,Betsi Cadwaladr University Health Board | Martyr A.,Bangor University | Clare L.,Bangor University
Parkinsonism and Related Disorders | Year: 2014

Background: The concept of cognitive reserve is proposed to explain the mismatch between the degree of pathological changes and their clinical manifestations and has been used to help understand the variation in the rate of cognitive decline and the development of dementias. It is not clear whether this concept applies to cognitive performance, cognitive decline and dementia in Parkinson's disease (PD). Methods: A systematic review was conducted using the most commonly described proxies for cognitive reserve of education, occupation and leisure activities. Thirty four papers were found on education and cognition in PD but there were no studies of the other proxies of reserve. A random effects meta-analysis was used to assess the associations between education and cross-sectional cognitive assessments, longitudinal global cognitive decline and a long term dementia diagnosis. Results: There was a significant association between higher education and cross-sectional performance of MMSE, global cognition, mild cognitive impairment, attention, executive function, visuospatial function and memory. There was a small but significant association between higher education and a reduced rate of cognitive decline. There was no association with a final dementia diagnosis. There was not enough information to perform an analysis on the rate and timing of transition to dementia. Conclusions: Higher levels of education are associated with significantly better cognitive performance and a small but significant slowing in cognitive decline but are not associated with a reduction in long-term dementia in PD. More detailed, standardized, longitudinal studies are required to study conclusively the effects cognitive reserve in PD. © 2013 Elsevier Ltd.

Kudlicka A.,Bangor University | Clare L.,Bangor University | Hindle J.V.,Bangor University | Hindle J.V.,Betsi Cadwaladr University Health Board
Movement Disorders | Year: 2011

Impairment of executive function (EF) is commonly reported as a feature of PD. However, the exact pattern of executive impairment remains unclear. Also, there is an ongoing discussion surrounding the definition and conceptualization of EF, which might affect the clarity of research evidence on cognition in PD. The aim of this systematic review was to describe the pattern of executive impairment in early-stage PD emerging from the research literature and to identify critical issues for improving consistency in this field. The PsychInfo, MEDLINE, Science Direct, CINAHL, and Cochrane Library databases were searched using the term "Parkinson's disease" combined with each of 14 cognitive abilities defined as representing aspects of EF. The review was limited to studies that investigated EF as the central variable in early-stage, nondemented PD patients. The review identified 33 studies of EF that were operationalized in terms of 30 abilities tested by 60 measures and variously interpreted. Many measures were used only once, so only a small part of the available research evidence could be synthesized in the meta-analysis. The meta-analysis was undertaken using data from five commonly used tests of EF drawn from 18 studies. This revealed consistent evidence for cognitive difficulties across all five EF tests. Research on EF in PD is characterized by a considerable lack of clarity with regard to measure selection and interpretation. The findings support the view that EF impairments are evident in PD. However, the clinical significance of the cognitive abnormalities reported has yet to be clarified. © 2011 Movement Disorder Society.

Davies K.E.,Betsi Cadwaladr University Health Board | Yesudian P.D.,Betsi Cadwaladr University Health Board
International Journal of Trichology | Year: 2012

Postoperative or pressure alopecia (PA) is an infrequently reported group of scarring and non-scarring alopecias. It has been reported after immobilization of the head during surgery and following prolonged stays on intensive care units, and may be analogous to a healed pressure ulcer. This review presents a summary of cases published in pediatrics and after cardiac, gynecological, abdominal and facial surgeries. PA may manifest as swelling, tenderness, and ulceration of the scalp in the first few postoperative days; in other cases, the alopecia may be the presenting feature with a history of scalp immobilization in the previous four weeks. The condition may cause considerable psychological distress in the long term. Regular head turning schedules and vigilance for the condition should be used as prophylaxis to prevent permanent alopecia. A multi-center study in high-risk patients would be beneficial to shed further light on the etiology of the condition.

Crossley D.R.,Betsi Cadwaladr University Health Board
Psychiatrist | Year: 2012

This article considers why whole-person care is often aspired to but remains problematic for psychiatry. One reason is that psychiatry wants to use ideas about the self in restricted senses rather than examine the idea as a whole. In particular, this includes wider issues that interconnect values to identity, which then ambiguously get raised in clinical practice, such as questions about who it is good to be. This issue is the context behind unresolved boundary disputes in mental health around well-being, spirituality, self-esteem and recovery, and reflects broader cultural tensions about the making of modern identity best understood in a historical context. It has impacts on service design, therapeutics and training. Suggestions are made about how the self can be approached in psychiatric practice.

Hobson P.,Betsi Cadwaladr University Health Board | Meara J.,Betsi Cadwaladr University Health Board
International Journal of Geriatric Psychiatry | Year: 2015

Objective Mild cognitive impairment in Parkinson's disease (PD-MCI) has been suggested to be a predictor for the development of PD dementia (PDD). This study explored the incidence and possible neuropsychological domain differences between PD patients with PD-MCI and without cognitive impairment (normal cognitive function with PD), on the basis of the Movement Disorders Task Force Guidelines for PD-MCI. Methods At baseline (T1), 4 years (T2) and 6 years (T3), 166 patients with PD were administered global neuropsychological assessments. At 16 years, case note and neuropsychological assessment review was employed to calculate the number of patients who had progressed to PDD. Results At baseline, 68 patients were classified as normal cognitive function with PD, 18 with PD-MCI and 80 with PDD. At T2, 12 of the PD-MCI cohort at T1 had progressed to PDD, and there were 15 incident cases of PD-MCI. At T3, nine PD-MCI cases at T2 had progressed to PDD. There were 10 incident cases of PD-MCI at T3. The incidence of progression from PD-MCI to PDD was 98.0 per 1000 person-years, with an annual conversion rate to PDD of 11%. Neuropsychological predictors for conversion from PD-MCI to PDD were semantic language, praxis (figure drawing/copying) and visuospatial deficits. At 16 years, 91% of the PD-MCI cohort had progressed to PDD. Conclusions Mild cognitive impairment in Parkinson's disease is an important predictor for the progression to PDD. This investigation also confirmed that if PD patients live long enough, they will develop cognitive impairment or dementia. Early detection of cognitive impairment in these individuals is possible with existing standardised global cognitive assessments, which include semantic language assessment. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

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