Reducing economic burden through split-shared care model for people living with uncontrolled type 2 diabetes and polypharmacy: a multi-center randomized controlled trial.

BACKGROUND: Interprofessional collaborative care such as a split-shared care model involving family physicians and community pharmacists can reduce the economic burden of diabetes management. This study aimed to evaluate the economic outcome of a split-shared care model between family physicians and community pharmacists within a pharmacy chain in managing people with uncontrolled type 2 diabetes and polypharmacy. METHOD: This was a multi-center, parallel arm, open label, randomized controlled trial comparing the direct and indirect economic outcomes of people who received collaborative care involving community pharmacists (intervention) versus those who received usual care without community pharmacist involvement (control). People with uncontrolled type 2 diabetes, defined as HbA1c > 7.0% and taking ≥ 5 chronic medications were included while people with missing baseline economic data (such as consultation costs, medication costs) were excluded. Direct medical costs were extracted from the institution's financial database while indirect costs were calculated from self-reported gross income and productivity loss, using Work Productivity Activity Impairment Global Health questionnaire. Separate generalized linear models with log link function and gamma distribution were used to analyze changes in direct and indirect medical costs. RESULTS: A total of 175 patients (intervention = 70, control = 105) completed the trial and were included for analysis. The mean age of the participants was 66.9 (9.2) years, with majority being male and Chinese. The direct medical costs were significantly lower in the intervention than the control group over 6 months (intervention: -US$70.51, control: -US$47.66, p < 0.001). Medication cost was the main driver in both groups. There were no significant changes in productivity loss and indirect costs in both groups. CONCLUSION: Implementation of split-shared visits with frontline community partners may reduce economic burden for patient with uncontrolled type 2 diabetes and polypharmacy. TRIAL REGISTRATION: Clinicaltrials.gov Reference Number: NCT03531944 (Date of registration: June 6, 2018).

Applying narrative medicine to prepare empathetic healthcare providers in undergraduate pharmacy education in Singapore: a mixed methods study.

BACKGROUND: Narrative medicine demonstrated positive impact on empathy in medicine and nursing students. However, this pedagogical approach had not been evaluated in pharmacy education. This study sought to apply and evaluate the narrative medicine approach in extending empathy in Asian undergraduate pharmacy students. METHODS: Narrative medicine was applied through workshops which used narratives of people with different experiences and perspectives. First-year undergraduate pharmacy students who volunteered and attended these workshops formed the intervention group (N = 31) and the remaining first-year cohort formed the control group (N = 112). A sequential explanatory mixed methods approach was adopted in which quantitative methods were first used to measure impact on pharmacy students' empathy using the Jefferson Scale of Empathy- Health Professions Student (JSE-HPS), and qualitative methods (i.e. group interviews) were then used to assess pharmacy students' emotional responses to narratives, and the perspectives of pharmacy students and faculty of this pedagogical approach. RESULTS: There was no difference in JSE-HPS scores between intervention and control groups across baseline (i.e. upon matriculation), pre-intervention, and post-intervention timepoints. Pharmacy students in the intervention group had lower scores in Factor 3 ("Standing in People's Shoes") following the intervention. Five themes, guided by internal and external factors in cognition, emerged from the Group Interviews: (1) incongruence between students' motivation and faculty's perception, (2) learning context, (3) academic context, (4) cognitive system, and (5) affective system. Themes 1, 4 and 5 referred to internal factors such as students' motivation, perceived learnings, and feelings. Themes 2 and 3 referred to external factors including workshop materials, activities, content, and facilitation. CONCLUSION: This study is the first to demonstrate that pharmacy students engaged with the narrative medicine approach as narratives elicited emotional responses, exposed them to diverse perspectives, and deepened their appreciation of the importance of empathy and complexities of understanding patients' perspectives. Scaffolded educational interventions using narratives and real-life patient encounters, alongside longitudinal measurements of empathy, are necessary to bring about meaningful and sustained improvements in empathy.

Chorea and polycythaemia vera.

We report two patients with chorea associated with polycythaemia vera, in whom the haematocrit and haemoglobin were within the reference range. Polycythaemia vera is potentially easily treatable and so is important to consider in people developing late-onset chorea.

Evaluating the internalisation of the intrinsic role of health advocacy of student pharmacists in a new integrated Bachelor of Pharmacy curriculum: a mixed-methods study.

To keep up with the contemporary health landscape, there is an imperative need for healthcare professionals to practise health advocacy through health promotion on the individual, population, and systems levels. In the Academic Year of 2020/2021, the National University of Singapore (NUS) Department of Pharmacy implemented a new spiral curriculum integrating basic, clinical, and systems sciences with one of its aims to deepen students' health advocacy internalisation and prepare them as future health advocates. A mixed-methods approach was adopted. Questionnaires were disseminated across three time-points to elicit students' levels of internalisation of health advocacy, which were then categorised into levels, and a Mann-Whitney U test was conducted. In comparison with prematriculation, no significant difference was found after students underwent the first year of the curriculum, while a significant difference was found after students underwent two years of the curriculum. Semi-structured interviews were also conducted after each Academic Year to gain deeper insights into the questionnaire results. Thematic analysis of the interviews revealed that curricular integration in the first year was perceived to be lacking. However, with learnt knowledge constantly reinforced and more experiential learning opportunities incorporated throughout the second year, students found the integrated curriculum beneficial in instilling confidence to practise health advocacy. This study offers insights into the prospects of a spiral integrated curriculum in imparting health advocacy, and may even suggest its potential to be applied to other educational settings. Future follow-up studies can also be conducted on the same study population to evaluate long-term impacts and areas for improvement of the curriculum.

A survey of nurse practitioner perceptions of integration into acute care organisations across one region in Ireland.

AIM: The purpose of the study was to explore nurse practitioner perceptions of integration practices in acute hospitals across one health care region in Ireland. BACKGROUND: A recent Department of Health National policy towards developing a critical mass of nurse practitioners was implemented across Ireland. Successful integration of nurse practitioner roles is integral to the success of the service and sustainability of the roles for the long term. METHOD: An electronic survey was circulated to a convenience sample of 85 nurse practitioners across a single, acute health care region in Ireland. RESULTS: Sixty-six (78%) of nurse practitioners participated. A standardized governance structure was reported by 24 (36%) participants. Thirty-two (48%) participants expressed their job description clearly defined their role. Consultant physicians were identified as the most supportive stakeholder by participants. CONCLUSIONS: This research identifies that nurse practitioner integration is not currently structured. A framework to support nurse practitioner integration is required to ensure ongoing support for the role. This research identifies that integration is not currently optimized. IMPLICATIONS FOR NURSING MANAGEMENT: Failure to successfully integrate the nurse practitioner role risks the long-term sustainability of the role and is a missed opportunity to demonstrate the success of advanced clinical leadership to health care.

Nursing and midwifery workforce readiness during a global pandemic: A survey of the experience of one hospital group in the Republic of Ireland.

AIM: To explore the mobilization of nurses/midwives in a designated hospital group in Ireland during a global pandemic. BACKGROUND: The recent global pandemic has resulted in the large-scale worldwide mobilization of registered nurses and midwives working in the acute care sector. There is a dearth of literature reporting the mobilization of this professional workforce. METHOD: Mixed-methods design using an electronic survey and facilitated discussion across one Irish hospital group. RESULTS: Eight of 11 hospitals responded to the survey. There was a 2% vacancy rate prior to the pandemic. Mobilization included reconfiguration of clinical areas and redeployment of 9% of the nursing/midwifery workforce within 2 weeks of the pandemic. A total of 11% (n = 343) of nurses/midwives were redeployed in 3 months. Nurses/midwives required re-skilling in infection prevention control, enhancement of critical care skills and documentation. CONCLUSIONS: Three key areas were identified to enable the nursing workforce readiness. These are referred to as the three 'R's': Reconfiguration of specific resources, Redeployment of nurses to dedicated specialist areas and Re-skilling of nurses to safely care for the patients during the pandemic. IMPLICATIONS FOR NURSING MANAGEMENT: A centralized approach to reconfiguration of clinical areas. Redeployment is enabled by closing non-essential departments. Hands-on re-skilling and reorientating staff are essential.

Deprescribing in older people approaching end-of-life: development and validation of STOPPFrail version 2.

BACKGROUND: Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy (STOPPFrail) criteria were developed in 2017 to assist physicians with deprescribing decisions in older people approaching end-of-life. Updating was required to make the tool more practical, patient-centred and complete. METHODS: a thorough literature review was conducted to, first, devise a practical method for identifying older people who are likely to be approaching end-of-life, and second, reassess and update the existing deprescribing criteria. An eight-member panel with a wide-ranging experience in geriatric pharmacotherapy reviewed a new draft of STOPPFrail and were invited to propose new deprescribing criteria. STOPPFrail version 2 was then validated using Delphi consensus methodology. RESULTS: STOPPFrail version 2 emphasises the importance of shared decision-making in the deprescribing process. A new method for identifying older people who are likely to be approaching end-of-life is included along with 25 deprescribing criteria. Guidance relating to the deprescribing of antihypertensive therapies, anti-anginal medications and vitamin D preparations comprises the new criteria. CONCLUSIONS: STOPPFrail criteria have been updated to assist physicians in efforts to reduce drug-related morbidity and burden for their frailest older patients. Version 2 is based on an up-to-date literature review and consensus validation by a panel of experts.

In-hospital adverse drug reactions in older adults; prevalence, presentation and associated drugs-a systematic review and meta-analysis.

BACKGROUND: the prevalence of adverse drug reactions (ADRs) in hospitalised older patients, their clinical presentations, causative drugs, severity, preventability and measurable outcomes are unclear, ADRs being an increasing challenge to older patient safety. METHODS: we systematically searched PubMed, Embase, EBSCO-CINAHL, the Cochrane Library, 'rey' literature and relevant systematic review bibliographies, published from database inception to March 2020. We included any study reporting occurrence of in-hospital ADRs as primary or secondary outcomes in hospitalised older adults (mean age ≥ 65 years). Two authors independently extracted relevant information and appraised studies for bias. Study characteristics, ADR clinical presentations, causative drugs, severity, preventability and clinical outcomes were analysed. Study estimates were pooled using random-effects meta-analytic models. RESULTS: from 2,399 abstracts, we undertook full-text screening in 286, identifying 27 studies (29 papers). Final analysis yielded a pooled ADR prevalence of 16% (95%CI 12-22%, I2 98%,τ2 0.8585), in a population of 20,153 hospitalised patients aged ≥65 years of whom 2,479 patients experienced ≥ one ADR. ADR ascertainment was highly heterogeneous. Almost 48.3% of all ADRs involved five presentations: fluid/electrolyte disturbances (17.3%), gastrointestinal motility/defaecation disorders (13.3%), renal disorders (8.2%), hypotension/blood pressure dysregulation disorders/shock (5.5%) and delirium (4.1%). Four drug classes accounted for 57.8% of causative medications i.e. diuretics (19.8%), anti-bacterials (14.8%), antithrombotic agents (12.2%) and analgesics (10.9%). Pooled analysis of severity was not feasible. Four studies reported the majority of ADRs as preventable (55-95%). CONCLUSIONS: on average, 16% of hospitalised older patients experience significant ADRs, varying in severity and mostly preventable, with commonly prescribed drug classes accounting for most ADRs.

Prevention of adverse drug reactions in hospitalized older patients with multi-morbidity and polypharmacy: the SENATOR* randomized controlled clinical trial.

BACKGROUND: Multi-morbidity and polypharmacy increase the risk of non-trivial adverse drug reactions (ADRs) in older people during hospitalization. Despite this, there are no established interventions for hospital-acquired ADR prevention. METHODS: We undertook a pragmatic, multi-national, parallel arm prospective randomized open-label, blinded endpoint (PROBE) controlled trial enrolling patients at six European medical centres. We randomized 1,537 older medical and surgical patients with multi-morbidity and polypharmacy on admission in a 1:1 ratio to SENATOR software-guided medication optimization plus standard care (intervention, n = 772, mean number of daily medications = 9.34) or standard care alone (control, n = 765, mean number of daily medications = 9.23) using block randomization stratified by site and admission type. Attending clinicians in the intervention arm received SENATOR-generated advice at a single time point with recommendations they could choose to adopt or not. The primary endpoint was occurrence of probable or certain ADRs within 14 days of randomization. Secondary endpoints were primary endpoint derivatives; tertiary endpoints included all-cause mortality, re-hospitalization, composite healthcare utilization and health-related quality of life. RESULTS: For the primary endpoint, there was no difference between the intervention and control groups (24.5 vs. 24.8%; OR 0.98; 95% CI 0.77-1.24; P = 0.88). Similarly, with secondary and tertiary endpoints, there were no significant differences. Among attending clinicians in the intervention group, implementation of SENATOR software-generated medication advice points was poor (~15%). CONCLUSIONS: In this trial, uptake of software-generated medication advice to minimize ADRs was poor and did not reduce ADR incidence during index hospitalization.

Adverse Drug Reactions in an Oncological Population: Prevalence, Predictability, and Preventability.

BACKGROUND: Our goal was to determine (a) the prevalence of multimorbidity and polypharmacy in patients with cancer and (b) the prevalence, predictability, and preventability of adverse drug reactions (ADRs) causing/contributing to hospitalization. MATERIALS AND METHODS: We conducted a 12-month prospective observational study of patients aged ≥16 years admitted to an oncology center. Older adults were aged ≥70 years. RESULTS: We enrolled 350 patients: 52.3% (n = 183) female, mean age 63.6 years (SD 12.1), 36.6% (n = 121) aged ≥70 years. Multimorbidity (≥2 conditions) was identified in 96.9%; 68% had ≥5 conditions. The median number of medications was 6 (interquartile range [IQR] 4-8); 47% were prescribed ≥6 medications and 11.4% ≥11 medications. Older adults had higher numbers of comorbid conditions (7 [IQR 5-10] vs. 5 [IQR 3-7]) and were prescribed more medications (median 7 [IQR 4-9] vs. 4 [IQR 2-7]). ADRs caused/contributed to hospitalization in 21.5% (n = 75): 35.8% (n = 72) of emergency admissions and 4.7% (n = 3) of elective admissions. The most common ADRs were neutropenia with infection (25.3%), dyspepsia/nausea/vomiting (20%), and constipation (20%). Causative medications included systemic anticancer therapies (SACTs; 53.3%), opioids (17.3%), corticosteroids (6.7%), and nonsteroidal anti-inflammatory drugs (5.3%). ADR prevalence was similar in older and younger adults secondary to SACTs (8.3% vs. 13.1%), non-cancer medications (10.7% vs. 8.3%), and both (0% vs. 1.3%). ADRs were predictable in 89.3% (n = 67), definitely avoidable in 29.3% (n = 22), and possibly avoidable in 33.3% (n = 25). No association was identified between ADRs and age, gender, daily medication number, length of stay, or death. No ADR predictor variables were identified by logistic regression. CONCLUSION: More than 21% of admissions to an oncology service are ADR-related. ADRs are caused by both SACTs and non-cancer-specific medications. The majority are predictable; ≥60% may be preventable. Patients with cancer have high levels of multimorbidity and polypharmacy, which require vigilance for related adverse outcomes. IMPLICATIONS FOR PRACTICE: A diagnosis of cancer often occurs in patients with multimorbidity and polypharmacy. Cancer can cause an altered physiological environment, placing patients at risk of drug-drug interactions, drug-disease interactions, and adverse drug reactions (ADRs). This study identified that ADRs caused or contributed to one in five hospital admissions of patients with cancer. ADRs were caused by systemic anticancer therapies (SACTs) in 53.3% of cases and non-cancer medications in 45.4% of cases, and a combination of both in 1.3%. ADRs occurred in similar frequencies in older and younger patients secondary to SACTs (8.3% vs. 13.1%, p = .295), non-SACTs (10.7% vs. 8.3%, p = .107), and a combination of both (0% vs. 1.3%, p = .240). The majority of ADRs were predictable (89.3%) and potentially preventable (62.6%). These findings support the need for increased awareness of medication-related adversity in patients with cancer and interventions to minimize their occurrence, thus supporting the American Society of Clinical Oncology guidelines that recommend adults ≥65 years of age receiving chemotherapy have geriatric assessment to identify medical and medication issues.

The Effectiveness of α2 Agonists As Sedatives in Pediatric Critical Care: A Propensity Score-Matched Cohort Study.

OBJECTIVES: There is limited evidence supporting the widespread use of α2 agonists (clonidine and dexmedetomidine) in pediatric critical care sedation. This study sought to test the association between the use of α2 agonists and enhanced sedation. DESIGN: A retrospective observational cohort study was conducted. Noninferiority of time adequately sedated (COMFORT Behavior Score 11-16) while mechanically ventilated was assessed. Secondarily, dosing of opioids and benzodiazepines was examined. SETTING: Two tertiary PICUs. PATIENTS: Children were classified into an exposed group, who received an α2 agonist as part of their sedation regimen, and an unexposed group. Groups were matched using propensity score analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-thousand eighty-five patients were included. The exposed group were adequately sedated 74% (95% CI, 72-75%) of the study time compared with the unexposed group at 70% (95% CI, 67-72%) giving a ratio of 1.06 (95% CI, 1.02-1.10) and a noninferior time adequately sedated. A decrease in time oversedated was observed with 8.1% (95% CI, 4.3-11.9%) less time classified as oversedated in the exposed group. Reduction in morphine use of 0.25 µg/kg/hr (95% CI, -0.68 to 1.18 µg/kg/hr) was not statistically significant. Midazolam use did not decrease and was statistically higher. CONCLUSIONS: Use of α2 agonists was associated with similar time adequately sedated as a matched unexposed group although no reduction in morphine or benzodiazepine coadministration was observed. There was a shift toward lighter sedation with α2 agonist use.

STOPPFrail (Screening Tool of Older Persons' Prescriptions in Frail adults with a limited life expectancy) criteria: application to a representative population awaiting long-term nursing care.

PURPOSE: STOPPFrail criteria highlight instances of potentially inappropriate medications (PIMs) in frailer older adults with poor 1-year survival prognosis. The objectives of this study were to (i) determine the proportion of older adults requiring long-term nursing care in whom STOPPFrail criteria are applicable, (ii) measure the prevalence of STOPPFrail PIMs, and (iii) identify risk factors for PIMs in this cohort. METHODS: We retrospectively reviewed applications for long-term nursing care to nursing homes in the Cork area over a 6-month period. We recorded diagnoses, medications, functional status, cognitive ability, frailty status, and applied STOPPFrail criteria as appropriate. RESULTS: We reviewed 464 applications; 38 were excluded due to incomplete information and 274 patients (64.3%) met STOPPFrail eligibility criteria (median age 83 years (IQR 77.25-88); 233 (54.7%) female). Those STOPPFrail eligible were prescribed 2194 medications (mean 8, (SD 4)), of which 828 (37.7%) were PIMs. At least one PIM was identified in 250 eligible patients (91.2%). The median number of PIMs was 3 (IQR 2-4), the most common being (i) medications without clear indication identified in 47.0% (n = 129) of patients, (ii) long-term high-dose proton pump inhibitors in 31.4% (n = 86), and (iii) statins in 29.6% (n = 81). For every additional medication prescribed, the odds of identifying a PIM increased by 58% (odds ratio 1.58, 95% CI 1.32-1.89, p < 0.001). CONCLUSION: Almost 65% of patients awaiting long-term care are eligible for the application of STOPPFrail criteria with over 90% prescribed at least one PIM. Transition to nursing home care represents an opportunity to review therapeutic appropriateness and goals of prescribed medications.

Deprescribing in multi-morbid older people with polypharmacy: agreement between STOPPFrail explicit criteria and gold standard deprescribing using 100 standardized clinical cases.

PURPOSE: Older people with advanced frailty are among the highest consumers of medications. When life expectancy is limited, some of these medications are likely to be inappropriate. The aim of this study was to compare STOPPFrail, a concise, easy-to-use, deprescribing tool based on explicit criteria, with gold standard, systematic geriatrician-led deprescribing. METHODS: One hundred standardized clinical cases involving 1024 medications were prepared. Clinical cases were based on anonymized hospitalized patients aged ≥ 65 years, with advanced frailty (Clinical Frailty Scale ≥ 6), receiving ≥ 5 regular medications, who were selected from a recent observational study. Level of agreement between deprescribing methods was measured by Cohen's kappa coefficient. Sensitivity and positive predictive value of STOPPFrail-guided deprescribing relative to gold standard deprescribing was also measured. RESULTS: Overall, 524 medications (51.2%) of medications prescribed to this frail, elderly cohort were potentially inappropriate by gold standard criteria. STOPPFrail-guided deprescribing led to the identification of 70.2% of the potentially inappropriate medications. Cohen's kappa was 0.60 (95% confidence interval 0.55-0.65; p < 0.001) indicating moderate agreement between STOPPFrail-guided and gold standard deprescribing. The positive predictive value of STOPPFrail was 89.3% indicating that the great majority of deprescribing decisions aligned with gold standard care. CONCLUSIONS: STOPPFrail removes an important barrier to deprescribing by explicitly highlighting circumstances where commonly used medications can be safely deprescribed in older people with advanced frailty. Our results suggest that in multi-morbid older patients with advanced frailty, the use of STOPPFrail criteria to address inappropriate polypharmacy may be reasonable alternative to specialist medication review.

Longitudinal prevalence of potentially serious alcohol-medication interactions in community-dwelling older adults: a prospective cohort study.

PURPOSE: This study aims to estimate (i) the prevalence of potentially serious alcohol-medication interactions in a nationally representative sample of older adults using the Potentially Serious Alcohol-Medication Interactions in Older adults (POSAMINO) criteria, and (ii) whether POSAMINO prevalence changes over time. METHODS: A prospective cohort study of adults aged ≥ 65 years, using data from the first three waves of The Irish Longitudinal Study on Ageing (TILDA). All 38 POSAMINO criteria were applied at each wave using respondents' information on regular medications and alcohol consumption. Multilevel logistic regression and negative binomial models were used to investigate whether the prevalence of POSAMINO varied over time. RESULTS: The overall prevalence of POSAMINO was 18% at baseline, with 8% at risk of one potentially serious alcohol-medication interaction, and 10% at risk of two or more. The most common POSAMINO involved cardiovascular (CVS) agents (15% baseline; 11% wave 2; 14% wave 3), followed by central nervous system (CNS) agents (4% baseline; 4% wave 2; 5% wave 3). Prevalence of any POSAMINO (AOR 0.94, 95% CI 0.81, 1.08) or number of POSAMINO criteria (AIRR 0.97, 95% CI 0.91, 1.04) did not change over time. Any POSAMINO and number of POSAMINO were associated with younger age, male sex and number of medications and chronic conditions. CONCLUSIONS: Potentially serious alcohol-medication interactions occurred in 18% of older adults in this study. Alcohol screening and brief interventions should be considered for high-risk groups at the point of prescribing, particularly among younger older adults, men and as patients receive more medications or develop additional illnesses.

Detection and prevention of adverse drug reactions in multi-morbid older patients.

Adverse drug reactions (ADRs) are a recognised unintentional form of iatrogenic harm, which commonly occur in older adults who have high levels of multi-morbidity and associated polypharmacy. Previous studies estimate that at least one in 10 hospitalised older patients will experience an ADR. While recent research indicates that this could be as high as 39% in hospitalised multi-morbid, older adults, up to two-thirds of these ADRs can be considered preventable and therefore potentially avoidable. In addition to increasing patient morbidity and contributing to avoidable mortality, there is an associated cost implication with ADR occurrence. This commentary summarises current mainstream research in terms of ADR detection, prediction and prevention in multi-morbid older patients. At present, the biggest barrier to understanding and comparing ADRs in the literature is the large heterogeneity that exists in the population and study methods. Furthermore, there is the lack of standardised universally accepted methodology for ADR prediction, detection, causality assessment and subsequent prevention in older people. Standard available methods of ADR prediction applied to a heterogeneous multi-morbid population are generally unsatisfactory. Without an instrument that consistently and reliably predicts ADR risk in a reproducible manner, ADR prevention in multi-morbid older patients is challenging. Further attention should be focused on the culprit drugs that commonly lead to major ADRs in older multi-morbid hospitalised patients with polypharmacy. Risk associated with particular drug classes may possibly predict ADR occurrence better than patient characteristics alone. Current research is examining this drug class focus for ADR prevention in multi-morbid older people.

Potentially serious alcohol-medication interactions and falls in community-dwelling older adults: a prospective cohort study.

OBJECTIVE: To investigate the association between potentially serious alcohol-medication interactions (POSAMINO criteria), hypothesised to increase the risk of falls in older adults, and falls in community-dwelling older adults at two and 4 years follow-up. DESIGN: A prospective cohort study. SETTING: The Irish Longitudinal Study on Ageing. SUBJECTS: A total of 1,457 community-dwelling older adults aged ≥65 years, with a complete alcohol and regular medication data to allow for the application of the POSAMINO criteria. OUTCOMES: Self-reported falls at 2 and 4 years follow-up, any falls (yes/no), injurious falls (yes/no) and number of falls (count variable). RESULTS: The number of participants who reported falling since their baseline interview at 2 and 4 years were 357 (24%) and 608 (41.8%), respectively; 145 (10%) reported an injurious fall at 2 years and 268 (18%) at 4 years. Median (IQR) number of falls was 1 (1-2) at 2 years and 2 (1-3) at 4 years. Exposure to CNS POSAMINO criteria, hypothesised to increase the risk of falls due primarily to increased sedation, was associated with a significantly increased risk for falling (adjusted relative risk (RR) 1.50, 95% confidence interval (CI) 1.21-1.88) and for injurious falls (adjusted RR 1.62, 95% CI: 1.03-2.55) at 4 years. These equate to an absolute risk of 19% for falling (95% CI: 5-33%) and 8% for injurious falls (95% CI, 4-20%) at 4 years. CONCLUSIONS: Assessment and management strategies to prevent falls in community-dwelling older adults should consider patients' alcohol consumption alongside their assessment of patient medications, particularly among those receiving CNS agents.

The effect of SENATOR (Software ENgine for the Assessment and optimisation of drug and non-drug Therapy in Older peRsons) on incident adverse drug reactions (ADRs) in an older hospital cohort - Trial Protocol.

BACKGROUND: The aim of this trial is to evaluate the effect of SENATOR software on incident, adverse drug reactions (ADRs) in older, multimorbid, hospitalized patients. The SENATOR software produces a report designed to optimize older patients' current prescriptions by applying the published STOPP and START criteria, highlighting drug-drug and drug-disease interactions and providing non-pharmacological recommendations aimed at reducing the risk of incident delirium. METHODS: We will conduct a multinational, pragmatic, parallel arm Prospective Randomized Open-label, Blinded Endpoint (PROBE) controlled trial. Patients with acute illnesses are screened for recruitment within 48 h of arrival to hospital and enrolled if they meet the relevant entry criteria. Participants' medical history, current prescriptions, select laboratory tests, electrocardiogram, cognitive status and functional status are collected and entered into a dedicated trial database. Patients are individually randomized with equal allocation ratio. Randomization is stratified by site and medical versus surgical admission, and uses random block sizes. Patients randomized to either arm receive standard routine pharmaceutical clinical care as it exists in each site. Additionally, in the intervention arm an individualized SENATOR-generated medication advice report based on the participant's clinical and medication data is placed in their medical record and a senior medical staff member is requested to review it and adopt any of its recommendations that they judge appropriate. The trial's primary outcome is the proportion of patients experiencing at least one adjudicated probable or certain, non-trivial ADR, during the index hospitalization, assessed at 14 days post-randomization or at index hospital discharge if it occurs earlier. Potential ADRs are identified retrospectively by the site researchers who complete a Potential Endpoint Form (one per type of event) that is adjudicated by a blinded, expert committee. All occurrences of 12 pre-specified events, which represent the majority of ADRs, are reported to the committee along with other suspected ADRs. Participants are followed up 12 (+/- 4) weeks post-index hospital discharge to assess medication quality and healthcare utilization. This is the first clinical trial to examine the effectiveness of a software intervention on incident ADRs and associated healthcare costs during hospitalization in older people with multi-morbidity and polypharmacy. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT02097654 , 27 March 2014.

Optimizing clonidine dosage for sedation in mechanically ventilated children: A pharmacokinetic simulation study.

BACKGROUND: Clonidine is in widespread off-label use as a sedative in mechanically ventilated children, despite limited evidence of efficacy. A variety of dosage regimens have been utilized in clinical practice and in research studies. Within these studies, clonidine has inconsistently shown useful sedation properties. One of the reasons attributed to the inconsistent signs of efficacy is suboptimal clonidine dosing. AIMS: This study aims to propose a target plasma concentration and simulate clonidine pharmacokinetics (PK) in a cohort of mechanically ventilated children to evaluate the adequacy of clonidine dosage regimens used in clinical practice and research studies. METHODS: A literature search was undertaken to identify a clonidine pharmaockinetic-pharmacodynamics (PKPD) model, from which a target concentration for sedation was defined. Using a previously published PK model, the projected plasma concentrations of 692 mechanically ventilated children (demographics taken from a recent study) were generated. Doses from recently published clinical studies were investigated. Adequacy of each regimen to attain therapeutic clonidine plasma concentrations was assessed. RESULTS: A target plasma concentration of above 2 µg/L was proposed. Nine dosage regimens (four intravenous boluses, four intravenous infusions, and one nasogastric route boluses) were evaluated ranging from 1 µg/kg eight hourly intravenous boluses to a regimen up to 3 µg/kg/hr continuous intravenous infusion. Regimens with a loading dose of 2 µg/kg followed by variable continuous infusion of up to 2 µg/kg/hr titrated according to sedation score appear most suitable. Doses should be halved in neonates. CONCLUSION: The variety of dosage regimens in the previous studies of clonidine along with difficulties in the conduct of interventional studies may have contributed to the lack of efficacy data to support its use. Simulations of clonidine plasma concentrations based on known population pharmacokinetic parameters suggest a loading dose followed by higher than current practice maintenance dose infusion is required to achieve adequate steady-state concentrations early in treatment. Further PKPD studies will aid in the determination of the optimal clonidine dosage regimen.

Determinants of intentions to monitor antihypertensive medication adherence in Irish community pharmacy: a factorial survey.

BACKGROUND: Community pharmacy represents an important setting to identify patients who may benefit from an adherence intervention, however it remains unclear whether it would be feasible to monitor antihypertensive adherence within the workflow of community pharmacy. The aim of this study was to identify facilitators and barriers to monitoring antihypertensive medication adherence of older adults at the point of repeat dispensing. METHODS: We undertook a factorial survey of Irish community pharmacists, guided by a conceptual model adapted from the Theory of Planned Behaviour (TPB). Respondents completed four sections, 1) five factorial vignettes (clinical scenario of repeat dispensing), 2) a medication monitoring attitude measure, 3) subjective norms and self-efficacy questions, and 4) demographic and workplace questions. Barriers and facilitators to adherence monitoring behaviour were identified in factorial vignette analysis using multivariate multilevel linear modelling, testing the effect of both contextual factors embedded within the vignettes (section 1), and respondent-level factors (sections 2-4) on likelihood to perform three adherence monitoring behaviours in response to the vignettes. RESULTS: Survey invites (n = 1543) were sent via email and 258 completed online survey responses were received; two-thirds of respondents were women, and one-third were qualified pharmacists for at least 15 years. In factorial vignette analysis, pharmacists were more inclined to monitor antihypertensive medication adherence by examining refill-patterns from pharmacy records than asking patients questions about their adherence or medication beliefs. Pharmacists with more positive attitudes towards medication monitoring and normative beliefs that other pharmacists monitored adherence, were more likely to monitor adherence. Contextual factors also influenced pharmacists' likelihood to perform the three adherence monitoring behaviours, including time-pressures and the number of days late the patient collected their repeat prescription. Pharmacists' normative beliefs and the number of days late the patient collected their repeat prescription had the largest quantitative influence on responses. CONCLUSIONS: This survey identified that positive pharmacist attitudes and normative beliefs can facilitate adherence monitoring within the current workflow; however contextual time-barriers may prevent adherence monitoring. Future research should consider these findings when designing a pharmacist-led adherence intervention to be integrated within current pharmacy workflow.

Assessing the Multidimensional Relationship Between Medication Beliefs and Adherence in Older Adults With Hypertension Using Polynomial Regression.

Background: The Necessity-Concerns Framework (NCF) is a multidimensional theory describing the relationship between patients' positive and negative evaluations of their medication which interplay to influence adherence. Most studies evaluating the NCF have failed to account for the multidimensional nature of the theory, placing the separate dimensions of medication "necessity beliefs" and "concerns" onto a single dimension (e.g., the Beliefs about Medicines Questionnaire-difference score model). Purpose: To assess the multidimensional effect of patient medication beliefs (concerns and necessity beliefs) on medication adherence using polynomial regression with response surface analysis. Methods: Community-dwelling older adults >65 years (n = 1,211) presenting their own prescription for antihypertensive medication to 106 community pharmacies in the Republic of Ireland rated their concerns and necessity beliefs to antihypertensive medications at baseline and their adherence to antihypertensive medication at 12 months via structured telephone interview. Results: Confirmatory polynomial regression found the difference-score model to be inaccurate; subsequent exploratory analysis identified a quadratic model to be the best-fitting polynomial model. Adherence was lowest among those with strong medication concerns and weak necessity beliefs, and adherence was greatest for those with weak concerns and strong necessity beliefs (slope ß = -0.77, p<.001; curvature ß = -0.26, p = .004). However, novel nonreciprocal effects were also observed; patients with simultaneously high concerns and necessity beliefs had lower adherence than those with simultaneously low concerns and necessity beliefs (slope ß = -0.36, p = .004; curvature ß = -0.25, p = .003). The difference-score model fails to account for the potential nonreciprocal effects. Conclusion: Results extend evidence supporting the use of polynomial regression to assess the multidimensional effect of medication beliefs on adherence.