Adverse Outcomes of Polypharmacy in Older People: Systematic Review of Reviews

ObjectivePolypharmacy is widespread among older people, but the adverse outcomes associated with it are unclear. We aim to synthesize current evidence on the adverse health, social, medicines management, and health care utilization outcomes of polypharmacy in older people.DesignA systematic review, of systematic reviews and meta-analyses of observational studies, was conducted. Eleven bibliographic databases were searched from 1990 to February 2018. Quality was assessed using AMSTAR (A Measurement Tool to Assess Systematic Reviews).Setting and participantsOlder people in any health care setting, residential setting, or country.ResultsTwenty-six reviews reporting on 230 unique studies were included. Almost all reviews operationalized polypharmacy as medication count, and few examined medication classes or disease states within this. Evidence for an association between polypharmacy and many adverse outcomes, including adverse drug events and disability, was conflicting. The most consistent evidence was found for hospitalization and inappropriate prescribing. No research had explored polypharmacy in the very old (aged ≥85 years), or examined the potential social consequences associated with medication use, such as loneliness and isolation.Conclusions and implicationsThe literature examining the adverse outcomes of polypharmacy in older people is complex, extensive, and conflicting. Until polypharmacy is operationalized in a more clinically relevant manner, the adverse outcomes associated with it will not be fully understood. Future studies should work toward this approach in the face of rising multimorbidity and population aging.     

Deprescribing perceptions and practice reported by multidisciplinary hospital clinicians after,and by medical students before and after,viewing an e-learning module

BackgroundThere are many barriers to deprescribing in the routine care of older inpatients with polypharmacy. Implementation is limited by factors related to clinicians, patients, and the acute care setting. A short (11 min) e-learning module for multidisciplinary hospital clinicians was developed to address two commonly reported barriers: awareness of polypharmacy and self-efficacy in deprescribing.Objectives1) Describe the level of awareness of polypharmacy and self-efficacy of deprescribing in multi-disciplinary hospital clinicians following completion of an online e-learning module; and 2) describe the immediate impact of an online educational module in awareness and self-efficacy of polypharmacy and deprescribing in senior medical students.MethodsA questionnaire was developed and administered to hospital clinicians following completion of the e-learning module. Senior medical students undertook the questionnaire pre- and post-module.ResultsOverall, 99 hospital clinicians with diverse clinical roles, experience, and ages, and 30 medical students completed the questionnaire. Although most (≥80%) hospital clinicians reported a general awareness of polypharmacy and deprescribing, there was moderate to low current activity in medication review and deprescribing, a perceived lack of role in medication review by junior doctors, and minimal knowledge of deprescribing tools. Use of a previously validated self-efficacy questionnaire showed lowest self-efficacy in domains related to developing deprescribing plans and implementing them. Pre-post analysis of medical student responses found a small statistically significant improvement following viewing the module in awareness of polypharmacy, deprescribing and deprescribing tools, perception of their role in deprescribing, and self-efficacy in planning and implementation of deprescribing decisions.ConclusionsHospital clinicians and senior medical students had limited self-efficacy in deprescribing and hospital clinicians reported they did not deprescribe frequently. Targets for educational and behavioral interventions were identified. A short e-learning module on polypharmacy and deprescribing may be a useful component of a multi-strategic intervention to implement deprescribing into routine inpatient care.     

Biomarkers in pharmacology and drug discovery

Biomarkers, quantitatively measurable indicators of biological or pathogenic processes, once validated play a critical role in disease diagnostics, the prediction of disease progression, and/or monitoring of the response to treatment. They may also represent drug targets. A number of different methods can be used for biomarker discovery and validation, including proteomics methods, metabolomics, imaging, and genome wide association studies (GWASs) and can be analysed using receiver operating characteristic (ROC) plots. The relative utility of single biomarkers compared to biomarker panels is discussed, along with paradigms for biomarker development, the latter in the context of three large-scale biomarker consortia, the Critical Path Predictive Safety Testing Consortium (PSTC), the NCI Early Detection Research Network (EDRN) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). The importance of systematic optimization of many parameters in biomarker analysis, including validation, reproducibility, study design, statistical analysis and avoidance of bias are critical features used by these consortia. Problems including introduction of bias into study designs, data reporting or data analysis are also reviewed.     

Association between polypharmacy and dementia – A systematic review and metaanalysis

Objective: The association between polypharmacy and dementia is controversial. This systematic review and meta-analysis aims to summarize existing literature concerning the association between polypharmacy and dementia.

Methods: A systematic literature review was performed by searching the EMBASE, PubMed, Scopus and International Pharmaceutical Abstract databases using terms related to polypharmacy and dementia. A meta-analysis was performed using random effect models.

Results: Seven studies were included in this meta-analysis. The included studies were of medium to high quality with a potential for publication bias. A strong association between polypharmacy and dementia was found (pooled adjusted risk ratio (aRR)?=?1.30 (95% CI: 1.16–1.46), I²?=?68%). Excessive polypharmacy was also strongly associated with dementia (pooled aRR?=?1.52 (95% CI: 1.39–1.67), I²?=?24%).

Conclusion: Pooled risk estimates from this meta-analysis showed that polypharmacy was associated with dementia. Although the causality of the relationship cannot be concluded from this analysis, the finding encourages the use of multidimensional assessment tools for dementia that includes the number of medications as a component.     

Development,validation and evaluation of the Goal-directed Medication review Electronic Decision Support System (G-MEDSS)©

Objectives1) To understand and investigate the experiences of accredited clinical pharmacists (ACP) using computerised clinical decision support systems (CCDSS) during medication reviews for older people, including those living with dementia; 2) To design, develop, validate, and evaluate a CCDSS that incorporates pharmacological and other deprescribing tools to aid person-centred management of high-risk medications in older adults living with and without dementia.MethodsThis study consisted of three phases and was designed on scenario-based methodology: a) the development phase, which included an exploratory survey and prototype building; b) the validation phase, which included qualitative data collection and usability testing with ACPs, general practitioners (GPs) and carers for people living with dementia; and c) the evaluation phase, using mixed-methods analyses.ResultsThe exploratory survey found that ACPs required a flexible, and reliable CCDSS to support them with clinical decisions regarding high-risk medication use in older adults. The Goal-directed Medication review Electronic Decision Support System (G-MEDSS)© was developed and validated using quantitative and qualitative feedback received from ACPs, GPs and carers for people with dementia. The mean (SD) System Usability Scale score was 69.0 (12.9), which indicated fair-good usability.Discussion and conclusionsInvolving end-users in the design process refined and improved the design of G-MEDSS, allowing for a person-centred and goal-directed delivery of pharmaceutical care. G-MEDSS allows healthcare practitioners conducting medication reviews for older adults living with and without dementia to tailor pharmaceutical care to meet their goals and preferences. Future studies may explore integration of G-MEDSS with prescribing or dispensing software.     

Poisonings requiring admission to the pediatric intensive care unit: A 5-year review

Background. Poisonings represent a significant number of preventable admissions to the pediatric intensive care unit (PICU), but data about poisonings requiring PICU-level care are limited. Objectives. To identify the demographics of patients admitted with poisonings and characterize their clinical courses related to their poisoning. Methods. All poisonings over a 5-year period (2008–2012) at an academic medical center in New England were retrospectively reviewed using electronic medical records in an observational case series. Poisonings were identified using key search terms within an admissions database. Results. There were 273 admissions for poisonings, which represent 8% of total PICU admissions over this time period. The poisonings were unintentional in 148 (54%) cases and intentional in 125 (46%). The vast majority of poisonings occurred in patients either 3 years or below (N = 121, 44%) or 13 years or above (N = 124, 45%). Most (96%) admissions were for less than 48 h and 41% were for less than 24 h. Mean PICU length of stay was 1.2 + 0.7 days. A total of 468 substances were ingested in 54 different drug classes, with analgesics and antidepressants being the most common. Eighty-five (31%) poisonings were polypharmaceutical. The most commonly used therapies were naloxone, activated charcoal, and benzodiazepines. Twenty-seven patients (10%) received mechanical ventilation. There was one fatality, an adolescent with a polypharmacy overdose in a suicide attempt. Conclusion. Pediatric poisonings are a significant percentage of admissions to the PICU. The majority of poisonings are non-fatal, require supportive care, close monitoring, and some specific treatment. Drug classes causing poisonings have changed to a higher percentage of opioids in younger patients and atypical antidepressants in adolescents.     

Melatonin dispensing and polypharmacy rates for New Zealand children with autism or attention deficit hyperactivity disorders: A nationwide pharmacoepidemiological study

BackgroundChronic insomnia is common in children with autism and Attention Deficit Hyperactivity Disorder (ADHD). Melatonin is often used to treat childhood insomnia. However, it may interact with other medications being used to manage other symptoms. This pharmacoepidemiological study examined the rates of general and psychotropic polypharmacy among children with autism and/or ADHD, stratified by melatonin dispensing. The impact of sociodemographic and child characteristics on such dispensing was also examined.MethodLinked national health and pharmaceutical administrative data for children aged 0–18 years in 2019 was utilized. Overall and melatonin dispensing stratified polypharmacy rates were calculated. Ordinal logistic regression models were employed to compare groups and adjust for confounders.ResultsData were acquired for 10,209 children with autism (18.5% were dispensed melatonin), 5970 with ADHD (22.3% were dispensed melatonin), 2064 with autism and ADHD (29.9% were dispensed melatonin), and 1156,296 without a diagnosis of autism or ADHD (a control group; 0.5% dispensed melatonin). Relative to controls, rates of melatonin dispensing and polypharmacy were higher in children with autism and ADHD, and highest among those with both conditions. Children dispensed melatonin experienced the greatest rates of polypharmacy, especially if they had both autism and ADHD.ConclusionsChildren with autism and ADHD experience significant medication burden and potentially adverse interactions between psychotropic and sleep-related medication, raising important questions regarding their clinical care.