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

Cholinesterase inhibitors for Parkinson's disease dementia

Background - The loss of cholinergic, dopaminergic and noradrenergic innervations seen in Parkinson's Disease Dementia (PDD) suggest a potential role for cholinesterase inhibitors. Concerns have been expressed about a theoretical worsening of Parkinson's disease related symptoms, particularly movement symptoms. Objectives - To assess the efficacy, safety, tolerability and health economic data relating to the use of cholinesterase inhibitors in PDD. Search methods - The trials were identified from the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 19 April 2005 using the search term parkinson*. This register contains records from major health care databases and many ongoing trial databases and is updated regularly. Comprehensive searches of abstracts from major scientific meetings were performed. Pharmaceutical companies were approached for information regarding additional and ongoing studies. Selection criteria - Randomized, double-blind, placebo-controlled studies assessing the effectiveness of cholinesterase inhibitors in PDD. Inclusion and exclusion criteria were stated to limit bias. Data collection and analysis - Two reviewers (IM, CF) independently reviewed the quality of the studies utilizing criteria from the Cochrane Collaboration Handbook. Medications were examined separately and as a group. The outcome measures assessed were in the following domains: neuropsychiatric features, cognition, global impression, daily living activities, quality of life, burden on caregiver, Parkinsonian related symptoms, treatment acceptability as determined by withdrawal from trials, safety as determined by the frequency of adverse events, institutionalisation, death and health economic factors. Main results - A detailed and systematic search of relevant databases identified one published randomized, double-blind, placebo-controlled study (Emre 2004) involving 541 patients that compared rivastigmine with placebo. Rivastigmine produced statistically significant improvements in several outcome measures. On the primary cognitive measure, the ADAS-Cog, rivastigmine was associated with a 2.80 point ADAS-Cog improvement [WMD -2.80, 95% Cl -4.26 to -1.34, P = 0.0002] and a 2.50 point ADCS-ADL improvement [95% Cl 0.43 to 4.57, P = 0.02] relative to placebo. Clinically meaningful (moderate or marked) improvement occurred in 5.3% more patients on rivastigmine, and meaningful worsening occurred in 10.1% more patients on placebo. Tolerability appeared to be a significant issue. Significantly more patients on rivastigmine dropped out of the study due to adverse events [62/362 versus 14/179, OR 2.44, 95% Cl 1.32 to 4.48, P = 0.004]. Nausea [20/179 versus 105/362, OR 3.25, 95% Cl 1.94 to 5.45, P < 0.00001], tremor [7/179 versus 37/362, OR 2.80, 95% Cl 1.22 to 6.41, P = 0.01] and in particular vomiting [3/179 versus 60/362, OR 11.66, 95% Cl 3.60 to 37.72, P < 0.0001] were significantly more common with rivastigmine. However, significantly fewer patients died on rivastigmine than placebo [4/362 versus 7/179, OR 0.27, 95% CI 0.08 to 0.95, P = 0.04] Authors' conclusions - Rivastigmine appears to improve cognition and activities of daily living in patients with PDD. This results in clinically meaningful benefit in about 15% of cases. There is a need for more studies utilising pragmatic measures such as time to residential care facility and both patient and carer quality of life assessments. Future trials should involve other cholinesterase inhibitors, utilise tools to analyse the data that limit any bias and measure health economic factors. It is unlikely that relying solely on the last observation carried forward (LOCF) is sufficient. Publication of the observed case data in the largest trial would assist (Emre 2004). Adverse events were associated with the cholinergic activity of rivastigmine, but may limit patient acceptability as evidenced by the high drop out rate in the active arm

Role of community pharmacists in the use of antipsychotics for behavioural and psychological symptoms of dementia (BPSD): A qualitative study

Objective This study aimed to use qualitative methodology to understand the current role of community pharmacists in limiting the use of antipsychotics prescribed inappropriately for behavioural and psychological symptoms of dementia. Design A qualitative study employing focus groups was conducted. Data were analysed using thematic analysis. Setting 3 different geographical locations in the England. Participants Community pharmacists (n=22). Results The focus groups identified an array of factors and constraints, which affect the ability of community pharmacists to contribute to initiatives to limit the use of antipsychotics. 3 key themes were revealed: (1) politics and the medical hierarchy, which created communication barriers; (2) how resources and remit impact the effectiveness of community pharmacy; and (3) understanding the nature of the treatment of dementia. Conclusions Our findings suggest that an improvement in communication between community pharmacists and healthcare professionals, especially general practitioners (GPs) must occur in order for community pharmacists to assist in limiting the use of antipsychotics in people with dementia. Additionally, extra training in working with people with dementia is required. Thus, an intervention which involves appropriately trained pharmacists working in collaboration with GPs and other caregivers is required. Overall, within the current environment, community pharmacists question the extent to which they can contribute in helping to reduce the prescription of antipsychotics

An exploratory study of the role of trust in medication management within mental health services

Objective - To develop understandings of the nature and influence of trust in the safe management of medication within mental health services. Setting - Mental health services in the UK. Method - Qualitative methods were applied through focus groups across three different categories of service user—older adult, adults living in the community and forensic services. An inductive thematic analysis was carried out, using the method of constant comparison derived from grounded theory. Main Outcome - Measure Participants’ views on the key factors influencing trust and the role of trust in safe medication management. Results - The salient factors impacting trust were: the therapeutic relationship; uncertainty and vulnerability; and social control. Users of mental health services may be particularly vulnerable to adverse events and these can damage trust. Conclusion - Safe management of medication is facilitated by trust. However, this trust may be difficult to develop and maintain, exposing service users to adverse events and worsening adherence. Practice and policy should be oriented towards developing trust

Medicines reconciliation in comparison with NICE guidelines across secondary care mental health organisations

Background Medicines reconciliation-identifying and maintaining an accurate list of a patient's current medications-should be undertaken at all transitions of care and available to all patients. Objective A self-completion web survey was conducted for chief pharmacists (or equivalent) to evaluate medicines reconciliation levels in secondary care mental health organisations. Setting The survey was sent to secondary care mental health organisations in England, Scotland, Northern Ireland and Wales. Method The survey was launched via Bristol Online Surveys. Quantitative data was analysed using descriptive statistics and qualitative data was collected through respondents free-text answers to specific questions. Main outcomes measure Investigate how medicines reconciliation is delivered, incorporate a clear description of the role of pharmacy staff and identify areas of concern. Results Forty-two (52 % response rate) surveys were completed. Thirty-seven (88.1 %) organisations have a formal policy for medicines reconciliation with defined steps. Results show that the pharmacy team (pharmacists and pharmacy technicians) are the main professionals involved in medicines reconciliation with a high rate of doctors also involved. Training procedures frequently include an induction by pharmacy for doctors whilst the pharmacy team are generally trained by another member of pharmacy. Mental health organisations estimate that nearly 80 % of medicines reconciliation is carried out within 24 h of admission. A full medicines reconciliation is not carried out on patient transfer between mental health wards; instead quicker and less exhaustive variations are implemented. 71.4 % of organisations estimate that pharmacy staff conduct daily medicine reconciliations for acute admission wards (Monday to Friday). However, only 38 % of organisations self-report to pharmacy reconciling patients' medication for other teams that admit from primary care. Conclusion Most mental health organisations appear to be complying with NICE guidance on medicines reconciliation for their acute admission wards. However, medicines reconciliation is conducted less frequently on other units that admit from primary care and rarely completed on transfer when it significantly differs to that on admission. Formal training and competency assessments on medicines reconciliation should be considered as current training varies and adherence to best practice is questionable

Medication management - the missing link in dementia interventions

Editoria

Medication management - the missing link in dementia interventions

Editoria