Drug Burden Research Articles

Associations between Drug Burden Index, medication appropriateness and patient-reported outcomes in the community pharmacy setting in Malaysia

The increasing complexity of drug regimens over time and the use of multiple medications exposes older patients to a greater risk of receiving inappropriate medications. This study investigated whether Drug Burden Index (DBI) and potentially inappropriate medications (PIMs) were associated with patient-reported health outcomes (PROs) in community-dwelling older adults (aged ≥ 60 years) in Malaysia. DBI was used to quantify patients’ exposure to anticholinergic and sedative medications in a cross-sectional sample of older individuals from the community pharmacy setting in Malaysia. PIMs (based on Beers criteria), potentially inappropriate prescribing (PIP; based on STOPP criteria) and polypharmacy (use of ≥ 5 concurrent medications) were used to quantify exposure to inappropriate medications. PROs were investigated using the Groningen Frailty Indicator (GFI) for frailty and older people’s quality of life-35 (OPQOL) for quality of life (QOL). The adjusted associations between DBI, medication inappropriateness and PROs were analyzed. More than half of the study participants received ≥ 1 anticholinergic or sedative medications (mean 0.47/participant; range 0.0–2.14). Prevalence of frailty was low (8.90% of patients), with a mean GFI score of 1.67 (range 1–8) and was significantly and positively correlated with DBI (r 0.253; p = 0.003). In multivariate logistic regression, frailty was found to be significantly associated with the odds of receiving DBI-associated medications (odds ratio 1.44; 95% CI 1.02–2.02, p = 0.039). Non-significant associations were found between DBI and QOL domains, except for a significant and positive correlation between the independence domain of OPQOL and PIP. This study indicates a significant relationship between drug burden measured by DBI and frailty measured by GFI. The prescribers managing various medical conditions of older people should consider frailty and other relevant physical health parameters as important health outcomes.

A Survey of Drug Burden in Patients Undergoing Maintenance Hemodialysis in Japan.

Objective This report presents a part of a survey pertaining to drug burden in maintenance hemodialysis patients in Japan. Methods A patient-reported questionnaire-based survey was conducted from September to November 2016 in six regions in Japan. Patients A total of 700 patients (50-79 years old) on maintenance hemodialysis for >3 years and members of the Japan Association of Kidney Disease Patients (JAKDP) were provided with the questionnaire. They were randomly selected using stratified sampling according to patient distribution observed from the Japanese Society for Dialysis Therapy Renal Data Registry (JSDT JRDR). Results A total of 524 (74.9%) patient questionnaires were evaluated [mean (standard deviation; SD) age, 66.6 (7.2) years; males, 63.4%; dialysis vintage, 16.9 (9.1) years]. Patients' age, gender, and regional distribution were similar to the JSDT JRDR. They were taking an average (SD) of 16.4 (8.34) and 16.3 (8.55) oral medications/day on dialysis and nondialysis days, respectively. A majority of the patients were taking ≥10 oral medications/day on dialysis (75.1%) and nondialysis (74.4%) days, with phosphate binders being the most taken (7.0 tablets/day). A similar proportion (74.4%, 72.9%, respectively) was taking ≥6 different types of oral medications/day. Most patients were taking oral medications 3 (31%, 33%), 4 (24%, 22%), and ≥5 times (31%, 30%) a day, respectively. The drug burden was similar on dialysis and nondialysis days and did not vary with dialysis vintage. Conclusion The number, type, and frequency of oral medications in maintenance hemodialysis patients are high in Japan. The proportion of phosphate binders was highest among the prescription medications.

Anticholinergic Drug Burden Tools/Scales and Adverse Outcomes in Different Clinical Settings: A Systematic Review of Reviews.

Cumulative anticholinergic exposure (anticholinergic burden) has been linked to a number of adverse outcomes. To conduct research in this area, an agreed approach to describing anticholinergic burden is needed. This review set out to identify anticholinergic burden scales, to describe their rationale, the settings in which they have been used and the outcomes associated with them. A search was performed using the Healthcare Databases Advanced Search of MEDLINE, EMBASE, Cochrane, CINAHL and PsycINFO from inception to October 2016 to identify systematic reviews describing anticholinergic burden scales or tools. Abstracts and titles were reviewed to determine eligibility for review with eligible articles read in full. The final selection of reviews was critically appraised using the ROBIS tool and pre-defined data were extracted; the primary data of interest were the anticholinergic burden scales or tools used. Five reviews were identified for analysis containing a total of 62 original articles. Eighteen anticholinergic burden scales or tools were identified with variation in their derivation, content and how they quantified the anticholinergic activity of medications. The Drug Burden Index was the most commonly used scale or tool in community and database studies, while the Anticholinergic Risk Scale was used more frequently in care homes and hospital settings. The association between anticholinergic burden and clinical outcomes varied by index and study. Falls and hospitalisation were consistently found to be associated with anticholinergic burden. Mortality, delirium, physical function and cognition were not consistently associated. Anticholinergic burden scales vary in their rationale, use and association with outcomes. This review showed that the concept of anticholinergic burden has been variably defined and inconsistently described using a number of indices with different content and scoring. The association between adverse outcomes and anticholinergic burden varies between scores and has not been conclusively established.

PIN55 - Estimating Health Outcomes in HIV Infected Patients Treated with a Dual Regimen of Dolutegravir and Rilpivirine in Europe

The long-term toxicity (LTT) of chronic human immunodeficiency virus (HIV) antiretroviral therapy (ART) is an important clinical consideration. A recent study has demonstrated that the fear of LTT (encompassing cardiovascular disease, renal disease and bone fractures) may also impact patient utility. Reducing drug burden via a streamlined 2-drug regimen (2DR), could ameliorate ART-associated LTT and improve patients’ quality of life (QoL), which traditionally is not the main endpoint in clinical trials. This study sought to estimate the impact of treatment with a streamlined 2DR of dolutegravir and rilpivirine (DTG/RPV) on LTT vs current triple ART (cART), regarding total life years (LYs), quality-adjusted life years (QALYs) and other health outcomes in a European setting. A lifetime analysis of DTG/RPV was undertaken using a previously published Markov model with health states reflecting CD4 cell count, viral load and death. The model was populated with efficacy and safety data derived from two phase III SWORD trials and DEXA sub-study. Patients were initiated in the model according to SWORD baseline characteristics under two scenarios: [A] no LTT; [B] LTT, and disutility associated with LTT, and with the fear of LTT, applied to cART based on baseline ART regimens. Discounting was applied as per French recommendations (4% up to 30 years, 2% thereafter). Under scenario A, LYs and QALYs for DTG/RPV were 15.01 (undiscounted: 25.79) and 11.30 (19.10), respectively, and 15.02 (25.80) and 11.31 (19.12) for cART, respectively. Under scenario B, LYs and QALYs for DTG/RPV were 15.01 (25.79) and 10.73 (17.79), respectively and 15.02 (25.80) and 9.96 (16.67) for cART, respectively. Reducing drug burden through the introduction of a streamlined 2DR with DTG/RPV may provide improved quality of life for those receiving long term ART for chronic HIV infection, through a reduction in LTT incidence and fear of toxicity outcomes.

Prevalence, risk factors and adverse outcomes of anticholinergic burden in patients with advanced chronic conditions at hospital admission.

To evaluate the anticholinergic burden (ACB), the risk factors associated with its onset and the clinical consequences for patients with advanced chronic conditions. A 10-month cross-sectional study was carried out in an acute hospital care geriatric unit. Patients with advanced chronic conditions were identified by the NECessity of PALliative care (NECPAL) test. The ACB was established using the Anticholinergic Drug Scale and Drug Burden Index (DBI) tools. Demographic, pharmacological and clinical patient data were collected with the objective of determining risk factors related to ACB. Measured clinical outcomes were the presence of acute confusional state, bone fractures, length of stay, mortality and 12-month survival rate. A total of 235 patients were recruited (mean age 86.80 years, SD 5.37 years; 65.50% women), and 82.10% (DBI) and 93.6% (Anticholinergic Drug Scale) of the patients were treated with anticholinergic medications. Excessive polypharmacy (≥10 drugs) was identified as a risk factor for the presence of anticholinergic medication (Anticholinergic Drug Scale: OR 6.26, 95% CI 1.38-28.42; DBI: OR 3.44, 95% CI 1.60-7.38). High anticholinergic burden (by DBI >2 points) was an independent risk factor for the presence of acute confusional state on hospital admission (OR 2.98, 95% CI 1.04-8.50). However, ACB was not related to bone fractures on admission, length of stay, mortality or survival. Patients with advanced chronic conditions are frequently treated with anticholinergic drugs, with excessive polypharmacy as a risk factor. Anticholinergic drugs are a risk factor for the presence of acute confusional state on hospital admission, but have no other effect in terms of morbimortality. Geriatr Gerontol Int 2018; 18: 1159-1165.

Interplay between adenosine receptor antagonist and cyclooxygenase inhibitor in haloperidol-induced extrapyramidal effects in mice.

Antipsychotic drugs are the mainstay of psychotic disorders. The 'typical' antipsychotic agents are commonly employed for the positive symptoms of schizophrenia, though at an expense of extrapyramidal side effects (EPS). In the present study, we employed haloperidol (HP)-induced catalepsy model in mice to evaluate the role of adenosine receptor antagonist and cyclooxygenase (COX) enzyme inhibitor in the amelioration of EPS. HP produced a full blown catalepsy, akinesia and a significant impairment in locomotion and antioxidant status. Pre-treatment with COX inhibitor; naproxen (NPx) and adenosine receptor antagonist; caffeine (CAF), showed a significant impact on HP-induced cataleptic symptoms. Adenosine exerts pivotal control on dopaminergic receptors and is also involved in receptor internalization and recycling. On the other hand, prostaglandins (PGs) are implicated as neuro-inflammatory molecules released due to microglial activation in both Parkinson's disease (PD) and antipsychotics-induced EPS. The involvement of these neuroeffector molecules has led to the possibility of use of CAF and COX inhibitors as therapeutic approaches to reduce the EPS burden of antipsychotic drugs. Both these pathways seem to be interlinked to each other, where adenosine modulates the formation of PGs through transcriptional modulation of COXs. We observed an additive effect with combined treatment of NPx and CAF against HP-induced movement disorder. These effects lead us to propose that neuromodulatory pathways of dopaminergic circuitry need to be explored for further understanding and utilizing the full therapeutic potential of antipsychotic agents.

The Association between Anticholinergic Drug Use and Rehabilitation Outcome in Post-Acute Hip Fractured Patients: A Retrospective Cohort Study.

Anticholinergic (AC) drugs are associated with significant impairment in cognitive and physical function which may affect rehabilitation in older people. We aimed to evaluate whether AC burden is associated with rehabilitation achievement in post-acute hip-fractured patients. A retrospective cohort study carried out in a post-acute geriatric rehabilitation center on 1019 hip-fractured patients admitted from January 2011 to October 2015. The Anticholinergic Cognitive Burden Scale (ACB) was used to quantify the AC burden. Main outcome measures included the Functional Independence Measure (FIM) instrument, motor FIM (mFIM), Montebello Rehabilitation Factor Score (MRFS) on the mFIM, and length of stay (LOS). The study population was divided into two groups: individuals with low admission AC burden (ACB≤1) and those with high admission AC burden (ACB≥2). The relationship between the admission AC burden and clinical, demographic and comorbidity variables was assessed using the Mann-Whitney and Chi square tests. A multiple linear regression model was used to estimate the association between admission AC burden and discharge FIM score after controlling for sociodemographic characteristics and chronic diseases. Patients with a high admission AC burden had a significantly higher rate of high education, a significantly lower rate reside at home, they waited a longer period of time from surgery to rehabilitation, were less independent pre-fracture, and presented with a higher rate of vascular disorders and depression compared with patients with a lower admission AC burden. These patients also exhibited a significantly lower FIM score on admission and at discharge, a lower FIM score change, and a lower achievement on the MRFS compared with patients with a lower admission AC burden. A multiple linear regression analysis showed that admission AC burden was significantly associated with the discharge FIM score after adjustment for confounding variables. High admission AC drug burden is significantly associated with less favorable discharge functional status in post-acute hip-fractured patients, independent of relevant risk factors.

A defined, plant-based diet utilized in an outpatient cardiovascular clinic effectively treats hypercholesterolemia and hypertension and reduces medications.

Cardiovascular disease (CVD) is a major economic burden in the United States. CVD risk factors, particularly hypertension and hypercholesterolemia, are typically treated with drug therapy. Five-year efficacy of such drugs to prevent CVD is estimated to be 5%. Plant-based diets have emerged as effective mitigators of these risk factors. The implementation of a defined, plant-based diet for 4 weeks in an outpatient clinical setting may mitigate CVD risk factors and reduce patient drug burden. Participants consumed a plant-based diet consisting of foods prepared in a defined method in accordance with a food-classification system. Participants consumed raw fruits, vegetables, seeds, and avocado. All animal products were excluded from the diet. Participant anthropometric and hemodynamic data were obtained weekly for 4 weeks. Laboratory biomarkers were collected at baseline and at 4 weeks. Medication needs were assessed weekly. Data were analyzed using paired-samples t tests and 1-way repeated-measures ANOVA. Significant reductions were observed for systolic (-16.6 mmHg) and diastolic (-9.1 mmHg) blood pressure (P < 0.0005), serum lipids (P ≤ 0.008), and total medication usage (P < 0.0005). Other CVD risk factors, including weight (P < 0.0005), waist circumference (P < 0.0005), heart rate (P = 0.018), insulin (P < 0.0005), glycated hemoglobin (P = 0.002), and high-sensitivity C-reactive protein (P = 0.001) were also reduced. A defined, plant-based diet can be used as an effective therapeutic strategy in the clinical setting to mitigate cardiovascular risk factors and reduce patient drug burden.

Low-dose NSAIDs reduce pain via macrophage targeted nanoemulsion delivery to neuroinflammation of the sciatic nerve in rat

Neuroinflammation involving macrophages elevates Prostaglandin E2, associated with neuropathic pain. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) inhibits cyclooxygenase, reducing PGE2. However, NSAIDs cause physiological complications. We developed nanoemulsions incorporating celecoxib and near infrared dye. Intravenous injected nanoemulsion is incorporated into monocytes that accumulate at the injury; revealed in live animals by fluorescence. A single dose (celecoxib 0.24 mg/kg) provides targeted delivery in chronic constriction injury rats, resulting in significant reduction in the visualized inflammation, infiltration of macrophages, COX-2 and PGE2. Animals exhibit relief from hypersensitivity persisting at least four-days. The total body burden of drug is reduced by >2000 fold over oral drug delivery.

In Memoriam: Darrell R. Abernethy 1949–2017

In Memoriam: Darrell R. Abernethy 1949–2017

In Memoriam: Darrell R. Abernethy, 1949–2017

In Memoriam: Darrell R. Abernethy, 1949–2017

Drug burden index to define the burden of medicines in older adults with intellectual disabilities: An observational cross-sectional study.

The drug burden index (DBI) is a dose-related measure of anticholinergic and sedative drug exposure. This cross-sectional study described DBI in older adults with intellectual disabilities (ID) and the most frequently reported therapeutic classes contributing to DBI and examined associations between higher DBI scores and potential adverse effects as well as physical function. This study analysed data from Wave 2 (2013/2014) of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA), a representative study on the ageing of people with ID in Ireland. Self- and objectively-reported data were collected on medication use and physical health, including health conditions. The Barthel index was the physical function measure. The study examined 677 individuals with ID, of whom 644 (95.1%) reported taking medication and 78.6% (n=532) were exposed to medication with anticholinergic and/or sedative activity. 54.2% (n=367) were exposed to high DBI score (≥1). Adjusted multivariate regression analysis revealed no significant association between DBI score and daytime dozing, constipation or falls. After adjusting for confounders (sex, age, level of ID, comorbidities, behaviours that challenge, history of falls), DBI was associated with significantly higher dependence in the Barthel index (P=0.002). This is the first time DBI has been described in older adults with ID. Scores were much higher than those observed in the general population and higher scores were associated with higher dependence in Barthel index activities of daily living.

Associations between the Drug Burden Index, Potentially Inappropriate Medications and Quality of Life in Residential Aged Care.

Inappropriate polypharmacy may negatively impact the quality of life of residents in aged care facilities, but it remains unclear which medications may influence this reduced quality of life. The objective of this study was to examine whether the Drug Burden Index and potentially inappropriate medications were associated with quality of life in older adults living in residential care with a high prevalence of cognitive impairment and dementia. We conducted cross-sectional analyses of 541 individuals recruited from 17 residential aged care facilities in Australia in the Investigating Services Provided in the Residential Environment for Dementia (INSPIRED) study. Quality of life was measured using the EuroQol Five Dimensions Questionnaire (a measure of generic quality of life) and the Dementia Quality of Life Questionnaire completed by the participant or a proxy. In the 100days prior to recruitment, 83.1% of the participants received at least one anticholinergic or sedative medication included in the Drug Burden Index and 73.0% received at least one potentially inappropriate medication according to the Beers Criteria. Multi-level linear models showed there was a significant association between a higher Drug Burden Index and lower quality of life according to the EuroQol Five Dimensions Questionnaire [β (standard error): -0.034 (0.012), p=0.006] after adjustment for potential confounding factors. Increasing numbers of potentially inappropriate medications were also associated with lower EuroQol Five Dimensions Questionnaire scores [-0.030 (0.010), p=0.003] and Dementia Quality of Life Questionnaire-Self-Report-Utility scores [-0.020 (0.009), p=0.029]. Exposure to both Drug Burden Index-associated medications and potentially inappropriate medications was associated with lower Dementia Quality of Life Questionnaire-Self-Report-Utility scores [-0.034 (0.017), p=0.049]. Exposure to anticholinergic and sedative medications and potentially inappropriate medications occurred in over three-quarters of a population of older adults in residential care and was associated with a lower quality of life.

Development and validation of an instrument for measuring the burden of medicine on functioning and well-being: the Medication-Related Burden Quality of Life (MRB-QoL) tool

ObjectiveMedication-related burden (MRB) is a negative experience with medicine, which may impact on psychological, social, physical and financial well-being of an individual. This study describes the development and initial validation...

Use of Anticholinergic Drugs and its Relationship With Psychological Well-Being and Mortality in Long-Term Care Facilities in Helsinki

ObjectivesTo assess the burden of drugs with anticholinergic properties (DAPs) and associated factors in long-term care facilities and to explore how psychological well-being and mortality are associated with the use of DAPs. DesignCross-sectional study and 1-year follow-up of all-cause mortality. Setting and ParticipantsAll 4449 older people (>65 years of age) living in nursing homes and assisted living facilities in Helsinki in 2011 were recruited. After refusals and excluding residents with severe dementia, 2432 participants remained. MeasurementsData on demographics, drug use, and medical history were collected by trained nurses using a structured assessment. Psychological well-being (PWB) of participants was assessed by 6 questions resulting in a validated PWB score (range 0–1). Mortality data were retrieved from central registers. The total number of anticholinergic drugs was determined according to the Anticholinergic Risk Scale. ResultsOf the participants, 51% used at least 1 DAP. DAP users were younger and had better cognition than nonusers. There was a linear relationship between the number of DAPs used and poorer PWB. A similar trend was present between the number of DAPs and poorer PWB both among those with and without depression and among those with and without functional dependency. No difference in mortality existed between DAP users and nonusers. ConclusionsDespite DAP users being younger and having better cognition, they had poorer PWB. Clinicians should carefully consider the potential benefits and harm when prescribing DAPs to older people.

Dolutegravir plus rilpivirine dual therapy in treating HIV-1 infection

ABSTRACTIntroduction: The HIV-infected population is aging and comorbidities and polypharmacological regimens are increasing. To reduce toxicity and drug burden researchers are evaluating the efficacy, safety and durability of dual therapies as a switch option in subjects who have achieved stable virologic suppression. Initially effective dual combinations relied on protease inhibitors but when dolutegravir, the first integrase inhibitor to display a high genetic barrier, became commercially available, many physicians began to use it in a variety of dual regimens, generating several observational cohorts.Areas covered: This review covers the most recent data from observational cohorts and randomized clinical trials concerning the switch to the dual combination of dolutegravir plus rilpivirine and the reasons that lead to consider this option. Also, viral failures, due to poor adherence or to other factors, and drug resistance are investigated. Articles which are searchable on MEDLINE/PubMed and from the main national/international congresses in the field of HIV therapy are reviewed.Expert opinion: The observation period for this regimen is getting longer and data showing its efficacy in maintaining HIV-1 RNA < 50 copies/mL are now consolidated. Metabolic data suggest some benefit in the lipid profile, improvement in bone mineral density and reduced bone reabsorption.

Assessment of geriatric predictors of adherence to Zoledronic acid treatment for osteoporosis: a prospective follow-up study

ABSTRACTObjectives Discontinuation of bisphosphonate treatment remains high even with the long acting parenteral options. Whether there are some unidentified causes of noncompliance more specific to aged individuals is unknown. The aim of this study was to investigate baseline predictors of adherence to Zoledronic acid (ZOL) infusions among non-demented older adults with osteoporosis.Methods Patients aged ≥ 65 years who received a first ever ZOL infusion for osteoporosis were prospectively enrolled. Risk factors for osteoporosis and fractures, comorbidities, geriatric assessment measures, including depression, and anticholinergic burden were determined at baseline. Adherence was defined as taking the next ZOL infusion at 12 months.Results A total of 187 participants were included (mean age: 75.7 ± 6.3 years, female: 77.5%). Adherence to the next ZOL infusion was 66.8% (n = 125). Non-adherent participants (n = 62, 33.2%) had significantly higher frequency of historical height decrease and depression at baseline. Poor adherence was associated with height decrease, presence of depression, and higher anticholinergic burden in univariate analysis. After adjustment for relevant confounders, fragility fracture history (OR: 0.38, 95%CI: 0.17–0.86, p = 0.020), depression (OR: 0.32, 95%CI: 0.12–0.82, p = 0.018), and higher anticholinergic burden (OR: 0.67, 95%CI: 0.49–0.93, p = 0.017) were the predictors of lower adherence to ZOL infusion.Conclusions The rate of adherence to the next ZOL infusion was still suboptimal among older women and men in this study. Past osteoporotic fractures, depression, and higher anticholinergic drug burden predicted poor ZOL adherence. It was a novel finding that drug-related anticholinergic side effects adversely influenced adherence to another medication without anticholinergic properties.

Drug Burden and its Association with Falls Among Older Adults in New Zealand: A National Population Cross-Sectional Study.

Adverse outcomes associated with advanced diseases are often exacerbated by polypharmacy. The current study investigated an association between exposure to anticholinergic and sedative medicines and falls in community-dwelling older people, after controlling for potential confounders. We conducted a retrospective cross-sectional study of a continuously recruited national cohort of community-dwelling New Zealanders aged 65 years and over. Participants had an International Resident Assessment Instrument-Home Care (interRAI-HC) assessment between 1 September 2012 and 31 January 2016. InterRAI-HC is a comprehensive, multi-domain, standardised assessment. This study captured 18 variables, including fall frequency, from the interRAI. These data were deterministically matched with the Drug Burden Index (DBI) for each participant, derived from an anonymised national dispensed pharmaceuticals database. DBI groupings were statistically ascertained, and ordinal regression models employed. Overall, there were 71,856 participants, with a mean age of 82.7years (range 65-106); 43,802 (61.0%) were female, and 63,578 (88.5%) were New Zealand European. In unadjusted and adjusted analyses, DBI groupings were related to falls (p<0.001). A DBI score >3 was associated with a 41% increase in falls compared with a DBI score of 0 (p<0.001). There was a 'dose-response' relationship between DBI levels and falls risk. DBI was found to be independently and positively associated with a greater risk of falls in this cohort after adjustment for 18 known confounders. We suggest that the DBI could be a valuable tool for clinicians to use alongside electronic prescribing to help reduce falls in older people.

The Delirium Drug Scale is associated to delirium incidence in the emergency department.

This study was an observational retrospective cross-sectional chart review study in patients aged 75 years and older. It was carried out in three emergency departments of a tertiary care university health center. Patients were included if a medication list was available. Delirium present upon admission was assessed during the first five days of admission. A total of 1,205 subjects were included in the analysis. The mean age was of 83.4 years, and 62.4% were female. The prevalence of delirium was 19.1%. A total of 745 patients (62%) were exposed to DDS medication. The relative risk for the low (1-2) and high (>2) exposure group according to the DDS score was of 1.26 (CI: 0.95; 1.66) and 2.18 (CI: 1.61; 2.96) compared to a score of 0. In the multivariate analysis, dementia, anxiety, insomnia, history of delirium, infection, and acute kidney failure were significantly associated to delirium. When adjusted for confounding variables, the DDS score was associated with the incidence of delirium with an odd ratio (OR) of 1.29 (CI: 1.16; 1.44). This study found that DDS score was associated with delirium incidence. The association persisted in the multivariate analysis adjusted for 26 known risks and precipitating factors for delirium.

Temporal Changes in Prescription of Neuropharmacologic Drugs and Utilization of Resources Related to Neurologic Morbidity in Mechanically Ventilated Children With Bronchiolitis.

Critically ill children with bronchiolitis may require neuropharmacologic medications and support for neuro-functional sequelae, but current practices are not well described. We aimed to describe recent trends in neuropharmacology and utilization of neuro-rehabilitation resources in mechanically ventilated children with bronchiolitis. Analysis of the multicenter Pediatric Health Information System database. Forty-seven U.S. children's hospitals. PICU patients less than 2 years old with bronchiolitis undergoing mechanical ventilation between 2006 and 2015. None. Annual rates of utilization of neuropharmacologic medications (sedatives, analgesics, etc) and of neuro-rehabilitation services (physical therapy, neurologic consultation, etc) over the 10-year study period were compared. Neuropharmacologic medications prescribed on greater than or equal to 2 days were extracted. Utilization of MRI of the brain, neurologic consultation, swallow evaluation, occupational therapy, and physical therapy was also extracted. Among 12,508 subjects, the median age was 2.8 months, ~50% had comorbid conditions, and the median duration of mechanical ventilation was 7 days. The percentage of children prescribed greater than or equal to five drugs/drug classes increased over the study period from 36.5% to 55.8% (p < 0.001). There were significant increases over time in utilization of 10 of the 15 individual drugs/drug classes analyzed. More than half of subjects (6,294 [50.3%]) received at least one service that evaluates/treats neurologic morbidity. There were significant increases in the use of greater than or equal to one service (36.3% in 2006 to 59.6% in 2015; p < 0.001) and in the use of greater than or equal to two services (20.8% to 34.8%; p < 0.001). Utilization of each of the five individual resources increased significantly during the study period, but use of vasoactive medications and mortality did not. Prescription of neuropharmacologic agents increased over time using metrics of both overall drug burden and specific drug usage. Concurrently, the utilization of services that evaluate and/or treat neurologic morbidity was common and also increased over time.