A pharmacy led program to review anti-psychotic prescribing for people with dementia

Background: Anti-psychotics, prescribed to people with dementia, are associated with approximately 1,800 excess annual deaths in the UK. A key public health objective is to limit such prescribing of anti-psychotics. Methods: This project was conducted within primary care in Medway Primary Care Trust (PCT) in the UK. There were 2 stages for the intervention. First, primary care information systems including the dementia register were searched by a pharmacy technician to identify people with dementia prescribed anti-psychotics. Second, a trained specialist pharmacist conducted targeted clinical medication reviews in people with dementia initiated on anti-psychotics by primary care, identified by the data search. Results: Data were collected from 59 practices. One hundred and sixty-one (15.3%) of 1051 people on the dementia register were receiving low-dose anti-psychotics. People with dementia living in residential homes were nearly 3.5 times more likely to receive an anti-psychotic [25.5% of care home residents (118/462) vs. 7.3% of people living at home (43/589)] than people living in their own homes (p?dementia register receiving low-dose anti-psychotics. Of the 161 people with dementia prescribed low-dose anti-psychotics, 91 were receiving on-going treatment from local secondary care mental health services or Learning Disability Teams. Of the remaining 70 patients the anti-psychotic was either withdrawn, or the dosage was reduced, in 43 instances (61.4%) following the pharmacy-led medication review. Conclusions: In total 15.3% of people on the dementia register were receiving a low-dose anti-psychotic. However, such data, including the recent national audit may under-estimate the usage of anti-psychotics in people with dementia. Anti-psychotics were used more commonly within care home settings. The pharmacist-led medication review successfully limited the prescribing of anti-psychotics to people with dementia.

'He was like a zombie':off-label prescription of antipsychotic drugs in dementia

This paper explores the legal position of the off-label prescription of antipsychotic medications to people with dementia who experience behavioural and psychological symptoms of dementia (BPSD). Dementia is a challenging illness, and BPSD can be very difficult for carers to manage, with evidence that this contributes to carer strain and can result in the early institutionalisation of people with dementia. As a result, the prescription of antipsychotic and other neuroleptic medications to treat BPSD has become commonplace, in spite of these drugs being untested and unlicensed for use to treat older people with dementia. In recent years, it has become apparent through clinical trials that antipsychotic drugs increase the risk of cerebrovascular accident (stroke) and death in people with dementia. In addition, these types of medication also have other risk factors for people with dementia, including over-sedation and worsening of cognitive function. Drawing on recent questionnaire (n = 185), focus group (n = 15), and interview (n = 11) data with carers of people with dementia, this paper explores the law relating to off-label prescription, and the applicability of medical negligence law to cases where adverse events follow the use of antipsychotic medication. It is argued that the practice of off-label prescribing requires regulatory intervention in order to protect vulnerable patients. © The Author [2012]. Published by Oxford University Press; all rights reserved.

The predictive ability of clinical tests for contact lens induced dry eye

Approximately half of current contact lens wearers suffer from dryness and discomfort, particularly towards the end of the day. Contact lens practitioners have a number of dry eye tests available to help them to predict which of their patients may be at risk of contact lens drop out and advise them accordingly. This thesis set out to rationalize them to see if any are of more diagnostic significance than others. This doctorate has found: (1) The Keratograph, a device which permits an automated, examiner independent technique for measuring non invasive tear break up time (NITBUT) measured NITBUT consistently shorter than measurements recorded with the Tearscope. When measuring central corneal curvature the spherical equivalent power of the cornea was measured as being significantly flatter than with a validated automated keratometer. (2) Non-invasive and invasive tear break-up times significantly correlated to each other, but not the other tear metrics. Symptomology, assessed using the OSDI questionnaire, correlated more with those tests indicating possible damage to the ocular surface (including LWE, LIPCOF and conjunctival staining) than with tests of either tear volume or stability. Cluster analysis showed some statistically significant groups of patients with different sign and symptom profiles. The largest cluster demonstrated poor tear quality with both non-invasive and invasive tests, low tear volume and more symptoms. (3) Care should be taken in fitting patients new to contact lenses if they have a NITBUT less than 10s or an OSDI comfort rating greater than 4.2 as they are more likely to drop-out within the first 6 months. Cluster analysis was not found to be beneficial in predicting which patients will succeed with lenses and which will not. A combination of the OSDI questionnaire and a NITBUT measurement was most useful both in diagnosing dry eye and in predicting contact lens drop out.

Medication -related adverse events in older people with dementia:causes and possible solutions

This submission for a PhD by previously published work is based upon six publications in peer reviewed journals, reflecting a 9-year research programme. My research has shown, in a coherent and original way, the difficulty in treating people with dementia with safe and effective medication whilst providing research-founded guidance to develop mechanisms to optimise medication choice and minimise iatrogenic events. A wide range of methods, including systematic reviews, meta-analysis, randomised controlled trials (RCTs), quantitative research and mixed methods were used to generate the data, which supported the exploration of three themes. The first theme, to understand the incidence and causes of medication errors in dementia services, identified that people with dementia may be more susceptible to medication-related iatrogenic disease partly due to inherent disease-related characteristics. One particular area of concern is the use of anti-psychotics to treat the Behavioural and Psychological Symptoms of Dementia (BPSD). The second and third themes, respectively, investigated a novel pharmacological and health services intervention to limit anti-psychotic usage. The second phase found that whilst the glutamate receptor blocker memantine showed some promise, further research was clearly required. The third phase found that anti-psychotic usage in dementia may be higher than official figures suggest and that medication review linking primary and secondary care can limit such usage. My work has been widely cited, reflecting a substantial contribution to the field, in terms of our understanding of the causes of, and possible solutions to limit, medication-related adverse events in people with dementia. More importantly, this work has already informed clinical practice, patients, carers and policy makers by its demonstrable impact on health policy. In particular my research has identified key lines of enquiry for future work and for the development of my own personal research programme to reduce the risk associated with medication in this vulnerable population.

Clinical evaluation of a multifocal aspheric diffractive intraocular lens

Aim: To evaluate the performance of an aspheric diffractive multifocal acrylic intraocular lens (IOL), ZMB00 1-Piece Tecnis. Setting: Five sites across Europe. Methods: Fifty-two patients with cataracts (average age 68.5±10.5 years, 35 female) were bilaterally implanted with the aspheric diffractive multifocal IOL after completing a questionnaire regarding their optical visual symptoms, use of visual correction and their visual satisfaction. The questionnaire was completed again 4-6 months after surgery along with measures of uncorrected and best-corrected distance and near visual acuity, under photopic and mesopic lighting, reading ability, defocus curve testing and ocular examination for adverse events. Results: The residual refractive error was 0.01±0.47D with 56% of eyes within ±0.25D and 97% within ±1.0D. Uncorrected visual acuity was 0.02±0.10logMAR at distance and 0.15±0.30 logMAR at near, only reducing to 0.07±0.10logMAR at distance and 0.21±0.25logMAR at near in mesopic conditions.The defocus curve showed a near addition between 2.5-3.0 D allowing a reading acuity of 0.08±0.13 logMAR, with a range of clear vision <0.3 logMAR of ∼4.0 D. The average reading speed was 121.4±30.8 words per minute. Spectacle independence was 100% for distance and 88% for near, with high levels of satisfaction reported. Overall rating of vision without glasses could be explained (r=0.760) by preoperative best-corrected distance acuity, postoperative reading acuity and postoperative uncorrected distance acuity in photopic conditions (p<0.001). Only two minor adverse events occurred. Conclusions: The ZMB00 1-Piece Tecnis multifocal IOL provides a good visual outcome at distance and near with minimal adverse effects.

A review of studies describing the use of acetyl cholinesterase inhibitors in Parkinson's disease dementia

Objective:  To review the literature relating to the use of acetyl cholinesterase inhibitors in Parkinson's disease dementia (PDD). Method:  MEDLINE (1966 – December 2004), PsychINFO (1972 – December 2004), EMBASE (1980 – December 2004), CINHAL (1982 – December 2004), and the Cochrane Collaboration were searched in December 2004. Results:  Three controlled trials and seven open studies were identified. Efficacy was assessed in three key domains: cognitive, neuropsychiatric and parkinsonian symptoms. Conclusion:  Cholinesterase inhibitors have a moderate effect against cognitive symptoms. There is no clear evidence of a noticeable clinical effect against neuropsychiatric symptoms. Tolerability including exacerbation of motor symptoms – in particular tremor – may limit the utility of cholinesterase inhibitors.

Systematic review investigating the reporting of comorbidities and medication in randomized controlled trials of people with dementia

Objectives: dementia is a debilitating condition characterised by global loss of cognitive and intellectual functioning, which reduces social and occupational performance. This population frequently presents with medical co-morbidities such as hypertension, cardiovascular disease and diabetes. The CONSORT statement outlines recommended guidance on reporting of participant characteristics in clinical trials. It is, however, unclear how much these are adhered to in trials assessing people with dementia. This paper assesses the reporting of medical co-morbidities and prescribed medications for people with dementia within randomised controlled trial (RCT) reports. Design: a systematic review of the published literature from the databases AMED, CINAHL, MEDLINE, EMBASE and the Cochrane Clinical Trial Registry from 1 January 1997 to 9 January 2014 was undertaken in order to identify RCTs detailing baseline medical co-morbidities and prescribed medications . Eligible studies were appraised using the Critical Appraisal Skills Programme (CASP) RCT appraisal tool, and descriptive statistical analyses were calculated to determine point prevalence. Results: nine trials, including 1474 people with dementia, were identified presenting medical co-morbidity data. These indicated neurological disorders ( prevalence 91%), vascular disorders (prevalence 91%), cardiac disorders ( prevalence 74%) and ischaemic cerebrovascular disease ( prevalence 53%) were most frequently seen. Conclusions: published RCTs poorly report medical co-morbidities and medications for people with dementia. Future trials should include the report of these items to allow interpretation of whether the results are generalisable to frailer older populations.

Corticobasal degeneration and dementia

Corticobasal degeneration is a rare, progressive neurodegenerative disorder which significantly impairs movement. The most common initial symptom is asymmetric limb clumsiness with or without accompanying rigidity or tremor. Subsequently, the disease progresses to affect gait and there is a slow progression to influence ipsilateral arms and legs. Apraxia and dementia are the most common cortical signs. Clinical diagnosis of the disorder is difficult as the symptoms resemble those of related neurodegenerative disorders. Histopathologically, there is widespread neuronal and glial pathology including tau-immunoreactive neuronal cytoplasmic inclusions, neuropil threads, oligodendroglial inclusions, astrocytic plaques, together with abnormally enlarged ‘ballooned’ neurons. Corticobasal degeneration has affinities both with the parkinsonian syndromes including Parkinson’s disease, progressive supranuclear palsy, and multiple system atrophy and with the fronto-temporal dementias. Treatment of corticobasal degeneration involves managing and reducing the effect of symptoms.

Discovering biomarkers for antidepressant response:protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods: CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion: From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. Trial registration: ClinicalTrials.gov identifier NCT01655706. Registered July 27, 2012.

Investigating the utility of clinical assessments to predict success with presbyopic contact lens correction

PURPOSE: To determine the utility of a range of clinical and non-clinical indicators to aid the initial selection of the optimum presbyopic contact lens. In addition, to assess whether lens preference was influenced by the visual performance compared to the other designs trialled (intra-subject) or compared to participants who preferred other designs (inter-subject). METHODS: A double-masked randomised crossover trial of Air Optix Aqua multifocal, PureVision 2 for Presbyopia, Acuvue OASYS for Presbyopia, Biofinity multifocal and monovision was conducted on 35 presbyopes (54.3±6.2years). Participant lifestyle, personality, pupil characteristics and aberrometry were assessed prior to lens fitting. After 4 weeks of wear, high and low contrast visual acuity (VA) under photopic and mesopic conditions, reading speed, Near Activity Visual Questionnaire (NAVQ) rating, subjective quality-of-vision scoring, defocus curves, stereopsis, halometry, aberrometry and ocular physiology were quantified. RESULTS: After trialling all the lenses, preference was mixed (n=12 Biofinity, n=10 monovision, n=7 Purevision, n=4 Air Optix Aqua, n=2 Oasys). Lens preference was not dependent on personality (F=1.182, p=0.323) or the hours spent working at near (p=0.535) or intermediate (p=0.759) distances. No intersubject or strong intrasubject relationships emerged between lens preference and reading speed, NAVQ rating, halo size, aberrometry or ocular physiology (p>0.05). CONCLUSIONS: Participant lifestyle and personality, ocular optics, contact lens visual performance and ocular physiology provided poor indicators of the preferred lens type after 4 weeks of wear. This is confounded by the wide range of task visual demands of presbyopes and the limited optical differences between current multifocal contact lens designs.

Survival in the pre-senile dementia frontotemporal lobar degeneration with TDP-43 proteinopathy:effects of genetic, demographic and neuropathological variables

Factors associated with survival were studied in 84 neuropathologically documented cases of the pre-senile dementia frontotemporal dementia lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). Kaplan-Meier survival analysis estimated mean survival as 7.9 years (range: 1-19 years, SD = 4.64). Familial and sporadic cases exhibited similar survival, including progranulin (GRN) gene mutation cases. No significant differences in survival were associated with sex, disease onset, Braak disease stage, or disease subtype, but higher survival was associated with lower post-mortem brain weight. Survival was significantly reduced in cases with associated motor neuron disease (FTLD-MND) but increased with Alzheimer's disease (AD) or hippocampal sclerosis (HS) co-morbidity. Cox regression analysis suggested that reduced survival was associated with increased densities of neuronal cytoplasmic inclusions (NCI) while increased survival was associated with greater densities of enlarged neurons (EN) in the frontal and temporal lobes. The data suggest that: (1) survival in FTLD-TDP is more prolonged than typical in pre-senile dementia but shorter than some clinical subtypes such as the semantic variant of primary progressive aphasia (svPPA), (2) MND co-morbidity predicts poor survival, and (3) NCI may develop early and EN later in the disease. The data have implications for both neuropathological characterization and subtyping of FTLD-TDP.