Rationalising antipsychotic prescribing in dementia: a mixed-methods investigation

Introduction: Antipsychotics are commonly prescribed to people with dementia, especially in nursing homes, despite limited benefits and significant harms. There have been calls to better understand the reasons why antipsychotics continue to be inappropriately prescribed to people with dementia, and to develop sustainable interventions. Hence the overarching aim of this thesis was to develop and assess the feasibility of a theoretically-informed, evidence-based and sustainable intervention to rationalise (or optimise) antipsychotic prescribing in nursing home residents with dementia. Methods: The overarching Medical Research Council (MRC) framework for developing and evaluating complex interventions guided our approach to this mixed-methods research. Firstly, a systematic review was undertaken to determine the effectiveness of pharmacists’ intervention in improving the appropriateness of prescribing in hospitalised older adults, with a particular focus on people with dementia. Secondly, a retrospective cross-sectional study was conducted examining prescribing differences between older adults with and without dementia, on admission to hospital. Next, a systematic review of qualitative evidence was undertaken to explore the influences on decision-making regarding antipsychotic prescribing in nursing home residents with dementia, which subsequently informed a semi-structured interview study exploring antipsychotic prescribing behaviours. The Behaviour Change Wheel (BCW) was then used to develop a complex intervention with Patient and Public Involvement (PPI) throughout. Finally, a feasibility study of the novel intervention was conducted in a nursing home setting. Results: Despite the fact that our cross-sectional study showed that hospitalised adults with dementia were prescribed significantly more antipsychotics, our systematic review found no pharmacist intervention existed which aimed to improve the quality of prescribing in this population. Our qualitative synthesis highlighted the complexity of decision-making with regards antipsychotic prescribing to nursing home residents with dementia. The interview study identified determinants influencing prescribing behaviours. Based on these findings, we developed the ‘Rationalising Antipsychotic Prescribing in Dementia’ (RAPID) complex intervention which consisted of academic detailing with general practitioners, education and training with nursing home staff, and an assessment tool. This intervention was found to be both feasible and acceptable, however limited uptake of the assessment tool compromised intervention implementation. Conclusion: This thesis has made a significant original contribution to knowledge, generating a much needed conceptual understanding of this complex issue and contributing towards intervention development. Further research is required to evaluate the effectiveness and sustainability of our novel intervention through larger scale evaluations

Patterns of psychotropic prescribing and polypharmacy in older hospitalized patients in Ireland: the influence of dementia on prescribing

Neuropsychiatric Symptoms (NPS) are ubiquitous in dementia and are often treated pharmacologically. The objectives of this study were to describe the use of psychotropic, anti-cholinergic, and deliriogenic medications and to identify the prevalence of polypharmacy and psychotropic polypharmacy, among older hospitalized patients in Ireland, with and without dementia. All older patients (≥ 70 years old) that had elective or emergency admissions to six Irish study hospitals were eligible for inclusion in a longitudinal observational study. Of 676 eligible patients, 598 patients were recruited and diagnosed as having dementia, or not, by medical experts. These 598 patients were assessed for delirium, medication use, co-morbidity, functional ability, and nutritional status. We conducted a retrospective cross-sectional analysis of medication data on admission for 583/598 patients with complete medication data, and controlled for age, sex, and co-morbidity. Of 149 patients diagnosed with dementia, only 53 had a previous diagnosis. At hospital admission, 458/583 patients experienced polypharmacy (≥ 5 medications). People with dementia (PwD) were significantly more likely to be prescribed at least one psychotropic medication than patients without dementia (99/147 vs. 182/436; p < 0.001). PwD were also more likely to experience psychotropic polypharmacy (≥ two psychotropics) than those without dementia (54/147 vs. 61/436; p < 0.001). There were no significant differences in the prescribing patterns of anti-cholinergics (23/147 vs. 42/436; p = 0.18) or deliriogenics (79/147 vs. 235/436; p = 0.62). Polypharmacy and psychotropic drug use is highly prevalent in older Irish hospitalized patients, especially in PwD. Hospital admission presents an ideal time for medication reviews in PwD

Influences on Decision-Making Regarding Antipsychotic Prescribing in Nursing Home Residents With Dementia: A Systematic Review and Synthesis of Qualitative Evidence.

BACKGROUND: Antipsychotic prescribing is prevalent in nursing homes for the management of behavioral and psychological symptoms of dementia (BPSD), despite the known risks and limited effectiveness. Many studies have attempted to understand this continuing phenomenon, using qualitative research methods, and have generated varied and sometimes conflicting findings. To date, the totality of this qualitative evidence has not been systematically collated and synthesized. AIMS: To synthesize the findings from individual qualitative studies on decision-making and prescribing behaviors for antipsychotics in nursing home residents with dementia, with a view to informing intervention development and quality improvement in this field. METHODS: A systematic review and synthesis of qualitative evidence was conducted (PROSPERO protocol registration CRD42015029141). Six electronic databases were searched systematically from inception through July 2016 and supplemented by citation, reference, and gray literature searching. Studies were included if they used qualitative methods for both data collection and analysis, and explored antipsychotic prescribing in nursing homes for the purpose of managing BPSD. The Critical Appraisal Skills Program assessment tool was used for quality appraisal. A meta-ethnography was conducted to synthesize included studies. The Confidence in the Evidence from Reviews of Qualitative research approach was used to assess the confidence in individual review findings. All stages were conducted by at least 2 independent reviewers. RESULTS: Of 1534 unique records identified, 18 met the inclusion criteria. Five key concepts emerged as influencing decision-making: organizational capacity; individual professional capability; communication and collaboration; attitudes; regulations and guidelines. A "line of argument" was synthesized and a conceptual model constructed, comparing this decision-making process to a dysfunctional negative feedback loop. Our synthesis indicates that when all stakeholders come together to communicate and collaborate as equal and empowered partners, this can result in a successful reduction in inappropriate antipsychotic prescribing. CONCLUSIONS: Antipsychotic prescribing in nursing home residents with dementia occurs in a complex environment involving the interplay of various stakeholders, the nursing home organization, and external influences. To improve the quality of antipsychotic prescribing in this cohort, a more holistic approach to BPSD management is required. Although we have found the issue of antipsychotic prescribing has been extensively explored using qualitative methods, there remains a need for research focusing on how best to change the prescribing behaviors identified

Identifying behavior change techniques for inclusion in a complex intervention targeting antipsychotic prescribing to nursing home residents with dementia

Nursing home residents with dementia are commonly prescribed antipsychotics despite the associated increased risk of harms. Interventions to optimize prescribing practice have been found to be effective in the short term, but there is a lack of evidence to support sustainability of effects, along with a lack of theory, public involvement, and transparency in the intervention development process. Using theory has been advocated as a means of improving intervention sustainability. The aim of this study was, therefore, to identify behavior change techniques (BCTs) for inclusion in a complex intervention targeting antipsychotic prescribing to nursing home residents with dementia. A comprehensive approach to identifying a long list of all potential BCTs from three different sources was undertaken. The most appropriate BCTs were then selected through a two-round Delphi consensus survey with a broad range of experts (n = 18 panelists). Advisory groups of people with dementia, family carers, and professional stakeholders provided feedback on the final BCTs included. After two Delphi survey rounds, agreement was reached on 22 BCTs. Further refinement of the selected BCTs based on advisory group and panelists' feedback, along with use of the APEASE criteria (Affordability, Practicability, Effectiveness, Acceptability, Side effects/safety, and Equity) resulted in a final list of 16 BCTs. The next step in intervention development will be to identify the most appropriate mode of delivery of the 16 BCTs identified for inclusion. The study provides a case example of a systematic approach to incorporating evidence with stakeholder views in the identification of appropriate BCTs

Stakeholders’ knowledge, attitudes and practices to pharmacovigilance and adverse drug reaction reporting in clinical trials: a mixed methods study

Purpose: The purpose of this study was to explore the knowledge, attitudes and practices of health professionals working in clinical trials, to pharmacovigilance and adverse drug reaction (ADR) reporting. Methods: A mixed methods study comprising an online questionnaire disseminated from September to November 2018, three semi-structured interviews and four focus groups. The qualitative components were conducted with a random sample of questionnaire participants who had provided their contact details (n = 24). The qualitative interviews were conducted at a location convenient to the participant’s place of work between October and December 2018. Results: One hundred forty-eight participants completed the questionnaire. Study coordinators/project managers represented the largest group of participants ( 28.6%, n = 38). Poor knowledge or understanding of ADR reporting was the most frequently cited barrier to ADR reporting (75%, n = 93). The most common enabler to reporting was having a clear understanding of an ADR definition (85.7%, n = 108). Focus group and interview participants described having limited staff as a barrier to reporting an ADR. They welcomed the prospect of pharmacovigilance training and indicated that face-to-face training would be preferred to provision of online training. Conclusion: This study highlights key factors that influence the reporting of ADRs in clinical trials. Although the findings are specifically related to the clinical trial environment in Ireland, they may provide a useful platform for optimising the future conduct of trials. This research suggests that ADR reporting may be improved through provision of enhanced pharmacovigilance training to clinical trial staff

Evaluation of an online interactive Diabetes Needs Assessment Tool (DNAT) versus online self-directed learning: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Methods for the dissemination, understanding and implementation of clinical guidelines need to be examined for their effectiveness to help doctors integrate guidelines into practice. The objective of this randomised controlled trial was to evaluate the effectiveness of an interactive online Diabetes Needs Assessment Tool (DNAT) (which constructs an e-learning curriculum based on individually identified knowledge gaps), compared with self-directed e-learning of diabetes guidelines.</p> <p>Methods</p> <p>Health professionals were randomised to a 4-month learning period and either given access to diabetes learning modules alone (control group) or DNAT plus learning modules (intervention group). Participants completed knowledge tests before and after learning (primary outcome), and surveys to assess the acceptability of the learning and changes to clinical practice (secondary outcomes).</p> <p>Results</p> <p>Sixty four percent (677/1054) of participants completed both knowledge tests. The proportion of nurses (5.4%) was too small for meaningful analysis so they were excluded. For the 650 doctors completing both tests, mean (SD) knowledge scores increased from 47.4% (12.6) to 66.8% (11.5) [intervention group (n = 321, 64%)] and 47.3% (12.9) to 67.8% (10.8) [control group (n = 329, 66%)], (ANCOVA p = 0.186). Both groups were satisfied with the usability and usefulness of the learning materials. Seventy seven percent (218/284) of the intervention group reported combining the DNAT with the recommended reading materials was "<it>very useful"/"useful"</it>. The majority in both groups (184/287, 64.1% intervention group and 206/299, 68.9% control group) [95% CI for the difference (-2.8 to 12.4)] reported integrating the learning into their clinical practice.</p> <p>Conclusions</p> <p>Both groups experienced a similar and significant improvement in knowledge. The learning materials were acceptable and participants incorporated the acquired knowledge into practice.</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN67215088">ISRCTN67215088</a></p

Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism.

BACKGROUND: The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. METHODS: We conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 μg daily, or 25 μg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points). RESULTS: The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 μg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% confidence interval [CI], -2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between-group difference, 0.4; 95% CI, -2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary-outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest. CONCLUSIONS: Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126 .)

Communicating complex ecological models to non-scientist end users

Complex computer models are used to predict how ecological systems respond to changing environ- mental conditions or management actions. Communicating these complex models to non-scientists is challenging, but necessary, because decision-makers and other end users need to understand, accept, and use the models and their predictions. Despite the importance of communicating effectively with end users, there is little guidance available as to how this may be achieved. Here, we review the challenges typically encountered by modellers attempting to communicate complex models and their outputs to managers and other non-scientist end users. We discuss the implications of failing to communicate effec- tively in each case. We then suggest a general approach for communicating with non-scientist end users. We detail the specific elements to be communicated using the example of individual-based models, which are widely used in ecology. We demonstrate that despite their complexity, individual-based models have characteristics that can facilitate communication with non-scientists. The approach we propose is based on our experiences and methods used in other fields, but which until now have not been synthesised or made broadly available to ecologists. Our aim is to facilitate the process of communicating with end users of complex models and encourage more modellers to engage in it by providing a structured approach to the communication process. We argue that developing measures of the effectiveness of communication with end users will help increase the impact of complex models in ecology

Group B streptococcus serotype prevalence in reproductive-age women at a tertiary care military medical center relative to global serotype distribution

<p>Abstract</p> <p>Background</p> <p>Group B <it>Streptococcus </it>(GBS) serotype (Ia, Ib, II-IX) correlates with pathogen virulence and clinical prognosis. Epidemiological studies of seroprevalence are an important metric for determining the proportion of serotypes in a given population. The purpose of this study was to evaluate the prevalence of individual GBS serotypes at Madigan Healthcare System (Madigan), the largest military tertiary healthcare facility in the Pacific Northwestern United States, and to compare seroprevalences with international locations.</p> <p>Methods</p> <p>To determine serotype distribution at Madigan, we obtained GBS isolates from standard-of-care anogenital swabs from 207 women of indeterminate gravidity between ages 18-40 during a five month interval. Serotype was determined using a recently described molecular method of polymerase chain reaction by capsular polysaccharide synthesis (cps) genes associated with pathogen virulence.</p> <p>Results</p> <p>Serotypes Ia, III, and V were the most prevalent (28%, 27%, and 17%, respectively). A systematic review of global GBS seroprevalence, meta-analysis, and statistical comparison revealed strikingly similar serodistibution at Madigan relative to civilian-sector populations in Canada and the United States. Serotype Ia was the only serotype consistently higher in North American populations relative to other geographic regions (p < 0.005). The number of non-typeable isolates was significantly lower in the study (p < 0.005).</p> <p>Conclusion</p> <p>This study establishes PCR-based serotyping as a viable strategy for GBS epidemiological surveillance. Our results suggest that GBS seroprevalence remains stable in North America over the past two decades.</p