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1.
Front Neurol ; 14: 1277765, 2023.
Article in English | MEDLINE | ID: mdl-38073643

ABSTRACT

Background: Stroke, even when minor, increases the risk of dementia. We aimed to determine whether patients with transient ischaemic attack (TIA) exhibit higher rates of cerebral and regional atrophy 1-year after first stroke symptoms and evaluate the relationship with small vessel disease and cognitive performance. Methods: TIA patients and controls without cognitive symptoms underwent high-resolution T1-weighted MRI and cognitive testing at baseline and 1-year. Percent brain volume change (PBVC) was measured, and the location of regional atrophy and small vessel disease (CSVD) burden was evaluated. Neuropsychological testing assessed memory, processing speed, and executive function. Results: A total of 76 TIA patients and 53 controls of mean age 67 (SD = 8) and 68 years (SD = 8) were recruited. TIA patients demonstrated greater improvement of visual memory and executive function at 1-year. TIA patients had greater median PBVC/year compared to controls (-0.79% [(-1.22)-(-0.38)] vs. -0.41% [(-0.62)-0.19]; p < 0.001), and higher rates of volume loss (ml/year) in subcortical gray (-0.53 [(-1.09)-(-0.06)] vs. -0.13 [(-0.61)-0.31]; p < 0.05) and white matter (-2.21 [-5.47, 0.40] vs. -0.93 [(-3.43)-2.10]; p < 0.05). Linear regression showed that TIA, age, and systolic blood pressure (SBP) were associated with greater cerebral volume loss over 1-year. There was no significant relationship between PBVC and 1-year cognition. Conclusion: A near two-fold increase in rate of cerebral atrophy 1-year after TIA is associated with higher SBP emphasizing the need for improved treatment of SBP. Cerebral and regional atrophy rates may be used to select patients for vascular risk reduction trials or novel therapeutics in future dementia prevention trials.

2.
Cereb Circ Cogn Behav ; 4: 100164, 2023.
Article in English | MEDLINE | ID: mdl-37124951

ABSTRACT

Background and Aims: Patients with transient ischemic attack (TIA) have a substantially increased risk of early dementia. In this exploratory study, we aim to determine whether patients with TIA have 1) measurable regional cerebral hypoperfusion unrelated to the location of ischemia, and 2) determine the relationship of regional cerebral blood flow (rCBF) with their cognitive profiles. Methods: Patients with TIA (N = 49) and seventy-nine (N = 79) age and sex matched controls underwent formal neuropsychological testing and MRI. Quantitative arterial spin labelling rCBF maps (mL/min/100 g) were registered to the corresponding high resolution T1-weighted image. Linear regression was used to determine the association between demographic, clinical and cognitive variables and rCBF. Results: Patients with TIA had significantly (p < 0.05) lower cognitive scores in the MMSE, MOCA, ACE-R, WAIS-IV DS Coding and Trail Making Tests A and B compared to controls. TIA patients had significantly lower rCBF in the left entorhinal cortex (p = 0.03), right posterior cingulate (p = 0.04), and right precuneus (p = 0.05), after adjusting for age and sex, that were unrelated to the regional anatomical volume and DWI positivity. Regional hypoperfusion in the right posterior cingulate and right precuneus was associated with impaired visual memory (BVMT total, p = 0.05 for both regions) and slower processing speed (TMT A, p = 0.04 and p = 0.01), respectively after adjusting for age and sex. Conclusions: TIA patients have patterns of regional hypoperfusion in multiple cortical regions unrelated to the parcellated regional anatomical volume or the presence of a DWI lesion. Regional hypoperfusion in patients with TIA may be an early marker conferring risk of future cognitive decline that needs to be confirmed by future studies.

3.
Front Oncol ; 12: 887653, 2022.
Article in English | MEDLINE | ID: mdl-36505832

ABSTRACT

Introduction: The aim of this study is to conduct a meta-analysis to assess the efficacy of yttrium-90 selective internal radiation therapy (SIRT) in treating patients with breast cancer with hepatic metastasis. Method: PubMed and The Cochrane Library were queried from establishment to January 2021. The following keywords were implemented: "breast", "yttrium", and "radioembolization". The following variables and outcomes were collected: publication year, region, sample size, study design, presence of extrahepatic disease, tumor burden, infused radioactivity, breast cancer subtype, previous treatment, median survival time (MST), length of follow-up, adverse events, and radiographical response such as Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Results: A total of 24 studies from 14 institutions were included in the present meta-analysis. On the basis of the data from 412 patients, post-embolization MST was 9.8 [95% confidence interval (CI): 9.0-11.6] months. Patients with additional extrahepatic metastasis had a poorer survival rate compared with those with localized hepatic metastasis only (MST: 5.3 vs. 15 months, p < 0.0001). Patients with <25% liver tumor burden exhibited more promising survival than those with >25% (MST: 10.5 vs. 6.8 months, p < 0.0139). On the basis of RECIST, mRECIST, and PERCIST criteria, tumor response rate was 36% (95% CI: 26%-47%), 49% (95% CI: 34%-65%), and 47% (95% CI: 17%-78%), respectively, whereas tumor control rate was 85% (95% CI: 76%-93%), 73% (95% CI: 59%-85%), and 97% (95% CI: 91%-100%), respectively. Conclusion: On the basis of the available published evidence, SIRT is feasible and effective in treating patients with breast cancer with liver metastasis. Patients with lower hepatic tumor burden and without extrahepatic metastasis demonstrated more survival benefit. Future randomized controlled trials are warranted.

4.
BMC Psychol ; 10(1): 161, 2022 Jun 26.
Article in English | MEDLINE | ID: mdl-35754046

ABSTRACT

BACKGROUND: Newly-qualified doctors in the United Kingdom experience a great deal of stress and have poor wellbeing when compared to more senior counterparts. A number of interventions have been put in place to boost healthcare professionals' wellbeing, but little is known about interventions aimed to improve the wellbeing of newly-qualified doctors in the United Kingdom. This study aims to systematically review current evidence of interventions which improved the wellbeing of newly-qualified junior doctors in the United Kingdom. METHODS: Five key electronic databases were searched. Subsequently, reference scanning and citation search was performed. Studies were included if they were conducted from the commencement of the Foundation Programme in 2004, until 2019. In addition, studies had to be performed on junior doctors: working in the United Kingdom and within their first five years post-qualification and have a quantitative outcome. Studies which did not meet these criteria were excluded. Quality was assessed using the modified Newcastle-Ottawa scale. Bias was not formally assessed using a standardised tool. RESULTS: Seven papers met the inclusion criteria and identified three main types of interventions: mentorship, mindfulness and clinical preparation interventions. The majority of included studies reported a positive result from the performed intervention, suggesting these to be beneficial in improving junior doctor wellbeing, and thereby reducing anxiety and stress levels. However, most of the studies used small sample sizes. CONCLUSIONS: This review reveals that there is dearth of evidence on the effectiveness of intervention to improve the wellbeing of newly-qualified doctors in the United Kingdom. Most of the identified interventions focused on relieving stress and anxiety inherent within newly-qualified doctors' training programmes. However, wellbeing interventions need to take into cognisance all the factors which impact on wellbeing, particularly job-related factors. We recommend that future researchers implement large-scale holistic interventions using appropriate research methods. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019127341.


Subject(s)
Mindfulness , Physicians , Health Personnel , Humans , United Kingdom
5.
Nat Med ; 28(6): 1240-1248, 2022 06.
Article in English | MEDLINE | ID: mdl-35577964

ABSTRACT

The timely identification of patients who are at risk of a mental health crisis can lead to improved outcomes and to the mitigation of burdens and costs. However, the high prevalence of mental health problems means that the manual review of complex patient records to make proactive care decisions is not feasible in practice. Therefore, we developed a machine learning model that uses electronic health records to continuously monitor patients for risk of a mental health crisis over a period of 28 days. The model achieves an area under the receiver operating characteristic curve of 0.797 and an area under the precision-recall curve of 0.159, predicting crises with a sensitivity of 58% at a specificity of 85%. A follow-up 6-month prospective study evaluated our algorithm's use in clinical practice and observed predictions to be clinically valuable in terms of either managing caseloads or mitigating the risk of crisis in 64% of cases. To our knowledge, this study is the first to continuously predict the risk of a wide range of mental health crises and to explore the added value of such predictions in clinical practice.


Subject(s)
Electronic Health Records , Mental Health , Humans , Machine Learning , Prospective Studies , ROC Curve
6.
J Am Heart Assoc ; 10(23): e022060, 2021 12 07.
Article in English | MEDLINE | ID: mdl-34796720

ABSTRACT

Background Both drug-coated balloon (DCB) angioplasty and conventional plain balloon angioplasty (PBA) can be implemented to treat hemodialysis dysfunction. The present study aims to compare the safety and efficacy of these 2 approaches by conducting a meta-analysis of available randomized controlled trials. Methods and Results PubMed, Cochrane Library, and Embase databases were queried from establishment to January 2021. A total of 18 randomized controlled trials including 877 and 875 patients in the DCB and PBA groups, respectively, were included in the present meta-analysis. Target lesion primary patency, circuit patency, target lesion revascularization, and mortality were pooled. Odds ratios (ORs) were reported with 95% CIs. Publication bias was analyzed with funnel plot and Egger test. Target lesion primary patency was higher among patients who underwent DCB (OR, 2.93 [95% CI, 2.13-4.03], P<0.001 at 6 months; OR, 2.47 [95% CI, 1.53-3.99], P<0.001 at 1 year). Also, the DCB group had a higher dialysis circuit patency at 6 months (OR, 2.42; 95% CI, 1.56-3.77 [P<0.001]) and 1 year (OR, 1.91; 95% CI, 1.22-3.00 [P=0.005]). Compared with the PBA group, the DCB group had lower odds of target lesion revascularization during follow-up (OR, 0.43 [95% CI, 0.23-0.82], P=0.001 at 6 months; OR, 0.74 [95% CI, 0.32-1.73], P=0.490 at 1 year). The OR of mortality was comparable between 2 groups at 6 months (OR, 1.18; 95% CI, 0.42-3.33 [P=0.760]) and 1 year (OR, 0.93; 95% CI, 0.58-1.48 [P=0.750]). Conclusions Based on evidence from 18 randomized controlled trials, DCB angioplasty is superior to PBA in maintaining target lesion primary patency and circuit patency among patients with dialysis circuit stenosis. DCB angioplasty also reduces target lesion revascularization with a similar risk of mortality compared with PBA.


Subject(s)
Angioplasty, Balloon , Renal Dialysis , Angioplasty, Balloon/methods , Humans , Randomized Controlled Trials as Topic , Treatment Outcome
7.
Ann Surg ; 274(5): 821-828, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34334637

ABSTRACT

OBJECTIVE: To define "best possible" outcomes for secondary bariatric surgery (BS). BACKGROUND: Management of poor response and of long-term complications after BS is complex and under-investigated. Indications and types of reoperations vary widely and postoperative complication rates are higher compared to primary BS. METHODS: Out of 44,884 BS performed in 18 high-volume centers from 4 continents between 06/2013-05/2019, 5,349 (12%) secondary BS cases were identified. Twenty-one outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of centers. Benchmark cases had no previous laparotomy, diabetes, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, thromboembolic events, BMI> 50 kg/m2 or age> 65 years. RESULTS: The benchmark cohort included 3143 cases, mainly females (85%), aged 43.8 ±â€Š10 years, 8.4 ±â€Š5.3 years after primary BS, with a BMI 35.2 ±â€Š7 kg/m2. Main indications were insufficient weight loss (43%) and gastro-esophageal reflux disease/dysphagia (25%). 90-days postoperatively, 14.6% of benchmark patients presented ≥1 complication, mortality was 0.06% (n = 2). Significantly higher morbidity was observed in non-benchmark cases (OR 1.37) and after conversional/reversal or revisional procedures with gastrointestinal suture/stapling (OR 1.84). Benchmark cutoffs for conversional BS were ≤4.5% re-intervention, ≤8.3% re-operation 90-days postoperatively. At 2-years (IQR 1-3) 15.6% of benchmark patients required a reoperation. CONCLUSION: Secondary BS is safe, although postoperative morbidity exceeds the established benchmarks for primary BS. The excess morbidity is due to an increased risk of gastrointestinal leakage and higher need for intensive care. The considerable rate of tertiary BS warrants expertise and future research to optimize the management of non-success after BS.


Subject(s)
Bariatric Surgery/standards , Benchmarking/standards , Elective Surgical Procedures/standards , Laparoscopy/standards , Obesity, Morbid/surgery , Adult , Female , Follow-Up Studies , Humans , Male , Prospective Studies , Reoperation
8.
Int J Geriatr Psychiatry ; 36(9): 1415-1422, 2021 09.
Article in English | MEDLINE | ID: mdl-33860554

ABSTRACT

INTRODUCTION: The number of people over the age of 65 attending Emergency Departments (ED) in the United Kingdom (UK) is increasing. Those who attend with a mental health related problem may be referred to liaison psychiatry for assessment. Improving responsiveness and integration of liaison psychiatry in general hospital settings is a national priority. To do this psychiatry teams must be adequately resourced and organised. However, it is unknown how trends in the number and type referrals of older people to liaison psychiatry teams by EDs are changing, making this difficult. METHODS: We performed a national multi-centre retrospective service evaluation, analysing existing psychiatry referral data from EDs of people over 65. We described trends in the number, rate, age, mental health presentation, and time taken to assessment over a 7 years period. RESULTS: Referral data from 28 EDs across England and Scotland were analysed (n = 18,828 referrals). There was a general trend towards increasing numbers of people referred to liaison psychiatry year on year. Variability in referral numbers between different departments, ranged from 0.1 to 24.3 per 1000 ED attendances. The most common reasons for referral were mood disorders, self-harm and suicidal ideas. The majority of referrals were assessed within 60 min, however there is variability between departments, some recording waits over 11 h. DISCUSSION: The data suggests great inter-departmental variability in referral numbers. Is not possible to establish the cause of variability. However, the data highlights the importance of asking further questions about why the differences exist, and the impact that has on patient care.


Subject(s)
Mental Disorders , Psychiatry , Aged , Emergency Service, Hospital , Humans , Mental Disorders/diagnosis , Mental Disorders/therapy , Referral and Consultation , Retrospective Studies , United Kingdom
9.
Alzheimers Res Ther ; 13(1): 47, 2021 02 17.
Article in English | MEDLINE | ID: mdl-33597002

ABSTRACT

BACKGROUND: Type 2 diabetes is a risk factor for Alzheimer's disease (AD), and AD brain shows impaired insulin signalling. The role of peripheral insulin resistance on AD aetiopathogenesis in non-diabetic patients is still debated. Here we evaluated the influence of insulin resistance on brain glucose metabolism, grey matter volume and white matter lesions (WMLs) in non-diabetic AD subjects. METHODS: In total, 130 non-diabetic AD subjects underwent MRI and [18F]FDG PET scans with arterial cannula insertion for radioactivity measurement. T1 Volumetric and FLAIR sequences were acquired on a 3-T MRI scanner. These subjects also had measurement of glucose and insulin levels after a 4-h fast on the same day of the scan. Insulin resistance was calculated by the updated homeostatic model assessment (HOMA2). For [18F]FDG analysis, cerebral glucose metabolic rate (rCMRGlc) parametric images were generated using spectral analysis with arterial plasma input function. RESULTS: In this non-diabetic AD population, HOMA2 was negatively associated with hippocampal rCMRGlc, along with total grey matter volumes. No significant correlation was observed between HOMA2, hippocampal volume and WMLs. CONCLUSIONS: In non-diabetic AD, peripheral insulin resistance is independently associated with reduced hippocampal glucose metabolism and with lower grey matter volume, suggesting that peripheral insulin resistance might influence AD pathology by its action on cerebral glucose metabolism and on neurodegeneration.


Subject(s)
Alzheimer Disease , Diabetes Mellitus, Type 2 , Insulin Resistance , Alzheimer Disease/complications , Alzheimer Disease/diagnostic imaging , Brain/diagnostic imaging , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnostic imaging , Fluorodeoxyglucose F18 , Glucose , Humans , Magnetic Resonance Imaging , Positron-Emission Tomography
10.
BJPsych Bull ; 45(3): 140-145, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33183400

ABSTRACT

AIMS AND METHOD: This study explored the root causes of deaths by suicide among patients under the care of a mental health trust. Thematic analysis was carried out to identify themes from the serious incident reports for patients between 1 January 2017 and 31 July 2018. RESULTS: In total, 48 cases were reviewed. Three main themes emerged from this study: patient-, professional- and organisation-related factors. The majority of the deaths were caused by patient-related factors, particularly exacerbation of the patient's mental health condition. CLINICAL IMPLICATIONS: This study provides insight into perceived causes of death by suicide among mental health patients. It is hoped that this will, in turn, influence the manner in which decisions, policies and resource allocation are carried out to further prevent and reduce the incidence of suicide, particularly among mental health patients.

11.
BMC Psychiatry ; 20(1): 587, 2020 12 10.
Article in English | MEDLINE | ID: mdl-33302905

ABSTRACT

BACKGROUND: Mental health crisis requiring emergency access to psychiatric service can occur at any time. Psychiatric Emergency Service (PES) is described as one that provides an immediate response to an individual in crisis within the first 24 h. Presently, several types of PESs are available in the United Kingdom (UK) with the aim of providing prompt and effective assessment and management of patients. Therefore, this study aims to provide a detailed narrative literature review of the various types of Psychiatric Emergency Service (PES) currently available in the UK. METHOD: Electronic search of five key databases (MEDLINE, PsychINFO, EMBASE, AMED and PUBMED) was conducted. Studies were included if it described a mental health service in the UK that provides immediate response in mental health crisis within the first 24 h. Excluded studies did not describe a PES, non-English, and were not conducted in UK. RESULTS: Nine types of PESs were found. Amongst the 9 services, more papers described crisis resolution home treatment. Majority of the papers reported services within England than other countries within the UK. CONCLUSION: All types of PESs were described as beneficial, particularly to mental health service users, but not without some shortcomings. There is a need to continue carrying out methodological research that evaluate impact, cost-effectiveness as well as identify methods of optimising the beneficial outcomes of the various types of PESs. This may help inform researchers, policy makers and commissioners, service users and carers, service providers and many more on how to ensure current and future PESs meet the needs as well as aid recovery during crisis.


Subject(s)
Emergency Services, Psychiatric , Mental Health Services , Cost-Benefit Analysis , England , Humans , United Kingdom
12.
Trials ; 21(1): 820, 2020 Sep 30.
Article in English | MEDLINE | ID: mdl-32998761

ABSTRACT

BACKGROUND: Cognitive impairment is common in haemodialysis (HD) patients and is associated independently with depression and mortality. This association is poorly understood, and no intervention is proven to slow cognitive decline. There is evidence that cooler dialysis fluid (dialysate) may slow white matter changes in the brain, but no study has investigated the effect of cooler dialysate on cognition. This study addresses whether cooler dialysate can prevent the decline in cognition and improve quality of life (QOL) in HD patients. METHODS: This is a multi-site prospective randomised, double-blinded feasibility trial. SETTING: Four HD units in the UK. PARTICIPANTS AND INTERVENTIONS: Ninety HD patients randomised (1:1) to standard care (dialysate temperature 36.5 °C) or intervention (dialysate temperature 35 °C) for 12 months. PRIMARY OUTCOME MEASURE: Change in cognition using the Montreal Cognitive Assessment (MoCA). SECONDARY OUTCOME MEASURES: Recruitment and attrition rates, reasons for non-recruitment, frequency of intradialytic hypotension, depressive symptom scores, patient and carers burden, a detailed computerised cognitive test and QOL assessments. ANALYSIS: mixed method approach, utilising measurement of cognition, questionnaires, physiological measurements and semi-structured interviews. DISCUSSION: The results of this feasibility trial will inform the design of a future adequately powered substantive trial investigating the effect of dialysate cooling on prevention and/or slowing in cognitive decline in patients undergoing haemodialysis using a computerised battery of neuro-cognitive tests. The main hypothesis that would be tested in this future trial is that patients treated with regular conventional haemodialysis will have a lesser decline in cognitive function and a better quality of life over 1 year by using cooler dialysis fluid at 35 °C, versus a standard dialysis fluid temperature of 36.5 °C. This also should reflect in improvements in their abilities for activities of daily living and therefore reduce carers' burden. If successful, the treatment could be universally applied at no extra cost. TRIAL REGISTRATION: ClinicalTrials.gov NCT03645733 . Registered retrospectively on 24 August 2018.


Subject(s)
Kidney Failure, Chronic , Quality of Life , Activities of Daily Living , Cognition , Feasibility Studies , Humans , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Prospective Studies , Randomized Controlled Trials as Topic , Renal Dialysis/adverse effects , Retrospective Studies
14.
JMIR Res Protoc ; 9(7): e14637, 2020 Jul 24.
Article in English | MEDLINE | ID: mdl-32706699

ABSTRACT

BACKGROUND: In Egypt, the population of older adults is rapidly growing. The last census in 2017 indicated that older adults numbered 94.8 million, which is a 2.56% increase from the 2006 census. There is growing evidence that the older population is at greater risk for some forms of mental disorders such as depression, dementia, and many more. OBJECTIVE: This study aims to review the current evidence regarding the prevalence of mental disorders among older adults in Egypt. This will be achieved by estimating the current prevalence of mental disorders and identifying any sociodemographic correlations with mental disorders. METHODS: An electronic search of 5 key databases (MEDLINE, PsycINFO, EMBASE, AMED, and PubMed) from their date of inception was conducted. In addition, scans of reference lists and searches of key journals, citations, and relevant internet resources were conducted. Studies were included if they were published in English, point prevalence studies, conducted with older Egyptians aged ≥60 years, and conducted using a validated diagnostic tool to ascertain mental disorders. Studies that did not meet any of these criteria were excluded. RESULTS: This systematic review started in November 2018. The literature search of the 5 databases revealed 343 papers. After screening titles and abstracts, scanning citations and reference lists, and searching internet sources, a total of 38 full-text articles were accessed, of which 16 studies met the eligibility criteria and were included. We are currently in the process of data extraction and synthesis. CONCLUSIONS: This research will help bring the scale of mental disorders among older adults in Egypt to the forefront. This may help ensure evidence-based initiatives are established and that priority is given to resource allocation for geriatric mental health in Egypt. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Review CRD42018114831; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=114831. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14637.

15.
ERJ Open Res ; 5(2)2019 Apr.
Article in English | MEDLINE | ID: mdl-31149625

ABSTRACT

There is increasing evidence demonstrating an association between chronic obstructive pulmonary disease (COPD) and cognitive impairment. We present a narrative review of published studies on the subject and a cross-sectional study investigating domain-specific cognitive impairment in people with COPD compared to people with known Alzheimer's dementia, and controls without known COPD or cognitive impairment. The aim of the study was to compare prevalence and pattern of cognitive impairment between the three groups using the Addenbrooke's Cognitive Examination (ACE)-III tool. A total of 89 participants were recruited (44 with COPD, 17 with Alzheimer's and 28 controls). Patients with COPD had significantly lower total ACE-III scores than controls (p<0.001). When comparing the COPD group to the known Alzheimer's dementia group, overall ACE-III scores were significantly lower in the Alzheimer's dementia group than the COPD group (p=0.019). The domain-specific scores for attention (p<0.004), memory (p<0.004) and fluency (p<0.001) were significantly lower in the Alzheimer's dementia group than the COPD group. Our result suggest that the COPD group were significantly more likely to have cognitive impairment than the healthy control group. This was supported by the results of a narrative review of the published literature. Our results show that the pattern of impairment in the COPD group is different to the pattern of impairment shown in the known Alzheimer's dementia group, with significant differences in the cognitive domains affected. These results are in keeping with the findings of other previously published studies included in the narrative review.

16.
Trials ; 20(1): 191, 2019 04 03.
Article in English | MEDLINE | ID: mdl-30944040

ABSTRACT

BACKGROUND: Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue currently approved for type 2 diabetes and obesity. Preclinical evidence in transgenic models of Alzheimer's disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells. The primary objective of the study is to evaluate the change in cerebral glucose metabolic rate after 12 months of treatment with liraglutide in participants with Alzheimer's disease compared to those who are receiving placebo. METHODS/DESIGN: ELAD is a 12-month, multi-centre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild Alzheimer's dementia. A total of 206 participants will be randomised to receive either liraglutide or placebo as a daily injection for a year. The primary outcome will be the change in cerebral glucose metabolic rate in the cortical regions (hippocampus, medial temporal lobe, and posterior cingulate) from baseline to follow-up in the treatment group compared with the placebo group. The key secondary outcomes are the change from baseline to 12 months in z scores for clinical and cognitive measures (Alzheimer's Disease Assessment Scale-Cognitive Subscale and Executive domain scores of the Neuropsychological Test Battery, Clinical Dementia Rating Sum of Boxes, and Alzheimer's Disease Cooperative Study-Activities of Daily Living) and the incidence and severity of treatment-emergent adverse events or clinically important changes in safety assessments. Other secondary outcomes are 12-month change in magnetic resonance imaging volume, diffusion tensor imaging parameters, reduction in microglial activation in a subgroup of participants, reduction in tau formation and change in amyloid levels in a subgroup of participants measured by tau and amyloid imaging, and changes in composite scores using support machine vector analysis in the treatment group compared with the placebo group. DISCUSSION: Alzheimer's disease is a leading cause of morbidity worldwide. As available treatments are only symptomatic, the search for disease-modifying therapies is a priority. If the ELAD trial is successful, liraglutide and GLP-1 analogues will represent an important class of compounds to be further evaluated in clinical trials for Alzheimer's treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01843075 . Registration 30 April 2013.


Subject(s)
Alzheimer Disease/drug therapy , Brain/drug effects , Glucagon-Like Peptide-1 Receptor/agonists , Glucose/metabolism , Hypoglycemic Agents/therapeutic use , Liraglutide/therapeutic use , Neuroprotective Agents/therapeutic use , Activities of Daily Living , Alzheimer Disease/metabolism , Alzheimer Disease/physiopathology , Alzheimer Disease/psychology , Brain/metabolism , Brain/physiopathology , Clinical Trials, Phase II as Topic , Cognition/drug effects , Double-Blind Method , Glucagon-Like Peptide-1 Receptor/metabolism , Humans , Hypoglycemic Agents/adverse effects , Liraglutide/adverse effects , Memory/drug effects , Multicenter Studies as Topic , Neuroprotective Agents/adverse effects , Randomized Controlled Trials as Topic , Severity of Illness Index , Time Factors , Treatment Outcome , United Kingdom
17.
Postgrad Med J ; 95(1119): 6-11, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30765421

ABSTRACT

BACKGROUND: Busy emergency departments (EDs) are not the optimum environment for assessment of patients in mental health crisis. The Psychiatric Decisions Unit (PDU) was developed by the Birmingham and Solihull Mental Health Foundation Trust as an enhanced assessment service to ensure patients in mental health crisis receive optimal care. AIMS: To evaluate the activities of the PDU and its impact on the frequency of ED presentations and inpatient admissions, and to explore patient satisfaction. METHODS: Data were collected over a 6-month period during 2015 regarding patient demographics, referral sources, length of stay, and frequency of mental health-related ED presentations and inpatient psychiatric admissions. Comparison group data were used to evaluate the impact of the PDU. Patient satisfaction was measured using the 'Friends and Family Test' and structured feedback forms. RESULTS: In total, 385 patients were referred to the PDU during the study period. Implementation of the PDU was associated with a 39% decrease in the number of patients taken to the ED by Street Triage and a 26% fall in inpatient psychiatric admissions via the Trusts' in-hospital liaison psychiatry team. Ninety-eight per cent of patients surveyed felt that they were treated with respect and understanding, and 94% reported that they were likely or extremely likely to recommend the service to friends and family. CONCLUSIONS: Implementation of the PDU was associated with a reduction in the frequency of ED presentations and inpatient psychiatric admissions. This study suggests that patients are satisfied with the care provided at the PDU.


Subject(s)
Emergency Service, Hospital/organization & administration , Emergency Services, Psychiatric/organization & administration , Mental Disorders/diagnosis , Patient Admission/statistics & numerical data , Adolescent , Adult , Aged , Child , England , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Patient Satisfaction , Referral and Consultation/statistics & numerical data , Surveys and Questionnaires
18.
Blood Purif ; 45(4): 347-355, 2018.
Article in English | MEDLINE | ID: mdl-29455207

ABSTRACT

INTRODUCTION: Cognitive impairment (CI) is very common condition that occurs in haemodialysis patients and it is associated with reduced functional capacity and mortality. We assessed the change in cognitive function during haemodialysis and associated risk factors. METHODS: All patients ≥50 years, on haemodialysis for ≥3 months, no dementia from 2 dialysis centres were selected. Cognition was assessed before and after a haemodialysis session using parallel versions of the Montreal Cognitive Assessment (MOCA) tool. Multiple regression was used to examine potential confounders. RESULTS: Eight-two patients completed both tests - median age 73 (52-91) years, 59% male, dialysis vintage 41 (3-88) months. Sixty-two (76%) had CI at baseline. Cognition declined over dialysis (MOCA 21 ± 4.8 to 19.1 ± 4.1, p < 0.001) and domains affected were attention, language, abstraction and delayed recall. Age and dialysis vintage were independently associated with decline. CONCLUSION: Cognitive function declines over a haemodialysis session and this has significant clinical implications over health literacy, self-management and tasks like driving. More research is needed to find the cause for this decline in cognition.


Subject(s)
Cognition , Cognitive Dysfunction , Renal Dialysis/adverse effects , Aged , Aged, 80 and over , Cognitive Dysfunction/etiology , Cognitive Dysfunction/physiopathology , Female , Humans , Male , Middle Aged , Risk Factors
19.
BMJ Case Rep ; 20172017 Oct 25.
Article in English | MEDLINE | ID: mdl-29070624

ABSTRACT

This is a case report of a man in his 60s who presented to an English hospital following a significant lithium overdose. He was monitored for 24 hours, and then renal replacement therapy was initiated after assessment by the renal team. As soon as the lithium level returned to normal therapeutic levels (from 4.7 mEq/L to 0.67 mEq/L), lithium was restarted by the medical team. At this point, the patient developed new slurred speech and later catatonia. In this case report, we discuss the factors that could determine which patients are at risk of neurotoxicity following lithium overdose and the appropriate decision regarding when and how to consider initiation of renal replacement therapy and restarting of lithium.


Subject(s)
Depressive Disorder/drug therapy , Drug Overdose/complications , Lithium/therapeutic use , Neurotoxicity Syndromes/etiology , Renal Replacement Therapy/methods , Humans , Lithium/blood , Male , Middle Aged , Neurotoxicity Syndromes/diagnosis , Neurotoxicity Syndromes/therapy , Suicidal Ideation , Treatment Outcome
20.
BJPsych Bull ; 40(4): 195-8, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27512588

ABSTRACT

Service development is guided by outcome measures that inform service commissioners and providers. Those in liaison psychiatry should be encouraged to develop a positive approach that integrates the collection of outcome measures into everyday clinical practice. The Framework for Routine Outcome Measurement in Liaison Psychiatry (FROM-LP) is a very useful tool to measure service quality and clinical effectiveness, using a combination of clinician-rated and patient-rated outcome measures and patient-rated experience measures. However, it does not include measures of cost-effectiveness or training activities. The FROM-LP is a significant step towards developing nationally unified outcome measures.

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