Delirium event and associated treatment modifications among older adults with Alzheimer's disease: An interrupted time-series analysis of Medicare data.

BACKGROUND: Both Alzheimer's disease (AD) and deliriogenic medications increase the risk of delirium in older adults. This study examined the association between delirium and the subsequent monthly use of anticholinergic, sedative, and opioid medications in the 1 year after delirium in older adults with AD. METHODS: This comparative interrupted time series analysis involved adults (aged 65 years and older) with a diagnosis of AD initiating on cholinesterase inhibitors (ChEIs) based on 2013-2017 Medicare data. Separate patient-level segmented regression models were used for each outcome to evaluate changes in the cumulative anticholinergic burden (CAB), sedative load, and opioid load after the delirium/index event using a 12-month baseline and follow-up period among patients who had a delirium event and those without delirium (control group). Propensity score-based stabilized weights were utilized to balance baseline factors in the delirium and control groups. RESULTS: The study included 80,019 older adults with AD with incident ChEI use; 17.11% had delirium. There was an immediate decline in monthly CAB after the delirium event (mean estimate -0.86, p-value: 0.01) compared to the control group. A similar decline was observed when examining the sedative load (-0.06, p-value: 0.002) after the delirium event. However, there was no decline in opioid load (-0.50, p-value: 0.18). In the long term, CAB (0.13; p-value: <0.0001), sedative load (0.01; p-value: <0.001), and opioid load (0.07; p-value: 0.006) increased over the 1-year post-delirium period in the delirium group compared to those without delirium. CONCLUSION: This study found the burden of deliriogenic medications over the 1-year follow-up showed increasing trends in older adults with AD, even though there was some level shift in CAB and sedative load after the delirium event.

Cumulative Anticholinergic Burden and its Predictors among Older Adults with Alzheimer's Disease Initiating Cholinesterase Inhibitors.

BACKGROUND: Cumulative anticholinergic burden refers to the cumulative effect of multiple medications with anticholinergic properties. However, concomitant use of cholinesterase inhibitors (ChEIs) and anticholinergic burden can nullify the benefit of the treatment and worsen Alzheimer's disease (AD). A literature gap exists regarding the extent of the cumulative anticholinergic burden and associated risk factors in AD. Therefore, this study evaluated the prevalence and predictors of cumulative anticholinergic burden among patients with AD initiating ChEIs. METHODS: A retrospective longitudinal cohort study was conducted using the Medicare claims data involving parts A, B, and D from 2013 to 2017. The study sample included older adults (65 years and older) diagnosed with AD and initiating ChEIs (donepezil, rivastigmine, or galantamine). The cumulative anticholinergic burden was calculated based on the Anticholinergic Cognitive Burden scale and patient-specific dosing using the defined daily dose over the 1 year follow-up period after ChEI initiation. Incremental anticholinergic burden levels were dichotomized into moderate-high (sum of standardized daily anticholinergic exposure over a year (TSDD) score ≥ 90) versus low-no (score 0-89). The Andersen Behavioral Model was used as the conceptual framework for selecting the predictors under the predisposing, enabling, and need categories. A multivariable logistic regression model was used to evaluate the predictors of high-moderate versus low-no cumulative anticholinergic burden. A multinomial logistic regression model was also used to determine the factors associated with patients having moderate and high burdens compared to low/no burdens. RESULTS: The study included 222,064 older adults with AD with incident ChEI use (mean age 82.24 ± 7.29, 68.9% females, 83.6% White). Overall, 80.48% had some anticholinergic burden during the follow-up, with 36.26% patients with moderate (TSDD scores 90-499), followed by 24.76% high (TSDD score > 500), and 19.46% with low (TSDD score 1-89) burden categories. Predisposing factors such as age; African American, Asian, or Hispanic race; and need factors included comorbidities such as dyslipidemia, syncope, delirium, fracture, pneumonia, epilepsy, and claims-based frailty index were less likely to be associated with the moderate-high anticholinergic burden. The factors that increased the odds of moderate-high burden were predisposing factors such as female sex; enabling factors such as dual eligibility and diagnosis year; and need factors such as baseline burden, behavioral and psychological symptoms of dementia, depression, insomnia, urinary incontinence, irritable bowel syndrome, anxiety, muscle spasm, gastroesophageal reflux disease, heart failure, and dysrhythmia. Most of these findings remained consistent with multinomial logistic regression.  CONCLUSION: Four out of five older adults with AD had some level of anticholinergic burden, with over 60% having moderate-high anticholinergic burden. Several predisposing, enabling, and need factors were associated with the cumulative anticholinergic burden. The study findings suggest a critical need to minimize the cumulative anticholinergic burden to improve AD care.

Risk of Serious Adverse Events Associated With Individual Cholinesterase Inhibitors Use in Older Adults With Dementia: A Population-Based Cohort Study.

BACKGROUND AND OBJECTIVE: Cholinesterase inhibitors (ChEIs) are used as first-line pharmacotherapy to manage dementia. However, there are limited data regarding their relative safety. This study evaluated the risk of serious adverse events (SAEs) associated with individual ChEIs in older adults with dementia and also examined sex-based and dose-based effects on this risk. METHODS: This was a retrospective cohort study using 2013-2015 US Medicare claims data involving Parts A, B, and D. Patients aged ≥ 65 years with a dementia diagnosis and incident use of the ChEIs, namely donepezil, galantamine, or rivastigmine, were included. The primary outcome of interest was SAEs defined as emergency department visits, inpatient hospitalizations, or death within 6 months of ChEI initiation. Multivariable Cox proportional hazards regression with propensity score (PS) as a covariate and inverse probability of treatment weighting generated using generalized boosted models was used to assess the risk of SAEs across individual ChEIs. RESULTS: The study included 767,684 older adults with dementia who were incident new users of ChEIs (donepezil 79.42%, rivastigmine 17.67%, galantamine 2.91%). SAEs were observed in 15.5% of the cohort within 6 months of ChEI prescription. Cox regression model with PS as covariate found that patients prescribed rivastigmine (adjusted hazard ratio [aHR] 1.12; 95% CI 1.03-1.33) and galantamine (aHR 1.51; 95% CI 1.24-1.84) were at increased risk of SAEs compared with patients on donepezil. Stratified analyses revealed that rivastigmine was associated with an 18% increased risk for SAEs in females (aHR 1.18; 95% CI 1.06-1.31), and galantamine was associated with a 71% increased risk in males (aHR 1.71; 95% CI 1.17-2.51) compared with donepezil. High and recommended index doses of rivastigmine and galantamine were associated with an increased risk of SAEs compared with donepezil. The findings were consistent in sensitivity analyses. CONCLUSION: The study found that the risk of SAEs varied across individual ChEIs, with sex and dose moderating these effects. Therefore, these moderating effects should be carefully considered in personalizing dementia care.

Risk of overactive bladder associated with cholinesterase inhibitors in dementia.

BACKGROUND: Although cholinesterase inhibitors (ChEIs) are the primary treatment for dementia, they are associated with overactive bladder (OAB), necessitating antimuscarinic use. Limited data exist regarding the risk of OAB across individual ChEIs in dementia. This study evaluated the risk of OAB associated with individual ChEIs in older adults with dementia. METHODS: This was a new user retrospective cohort study using Medicare claims data involving Parts A, B, and D claims dataset from 2013 to 2015. The study included older adults (aged 65 and older) with a diagnosis of dementia using donepezil, galantamine, or rivastigmine. New ChEI claims were identified with a 6-month baseline washout period. Patients with OAB diagnosis or any antimuscarinic or mirabegron use in the baseline period were excluded. The primary outcome of interest was OAB diagnosis or prescription of antimuscarinics or mirabegron within 6 months of ChEI initiation. Multivariable cox proportional hazards regression with propensity scores (PS) as covariates and inverse probability of treatment weighting generated using generalized boosted models was used to assess the risk of OAB among donepezil, galantamine, and rivastigmine users. RESULTS: The study included 524,975 older adults with dementia who were incident users of ChEIs (donepezil 80.72%, rivastigmine 16.41%, galantamine 2.87%). Overall, OAB diagnosis/antimuscarinic/mirabegron prescription was observed in 5.07% of the cohort within 6 months of ChEIs prescription. The Cox regression model with PS as covariate approach found that donepezil use increased the risk of OAB compared to rivastigmine (aHR, 1.13; 95% CI, 1.08-1.28; p < 0.0001). However, there was no differential risk of OAB between galantamine and rivastigmine. The findings were consistent with the generalized boosted models. CONCLUSIONS: The study found that the risk of OAB varies across individual ChEIs with an increased risk of OAB with donepezil compared to rivastigmine. The study findings suggest the need to understand and manage medication-related morbidity in older adults with dementia.

Antimuscarinic Cascade Across Individual Cholinesterase Inhibitors in Older Adults with Dementia.

BACKGROUND: Acetylcholinesterase inhibitors (AChEIs) have been associated with an increased risk of starting antimuscarinic treatment to treat overactive bladder (OAB)-an example of a prescribing cascade. Limited comparative data exist regarding the prescribing cascade of antimuscarinics across individual AChEIs in older adults with dementia. OBJECTIVE: This study examined the association between individual AChEI use and antimuscarinic cascade in older adults with dementia. METHODS: We conducted a new user retrospective cohort study from January 2005 to December 2018 using data from the TriNetX electronic medical record database, a federated electronic medical records network in the US. The cohort included patients 65 years or older with a diagnosis of dementia using AChEIs (donepezil, galantamine, or rivastigmine). Individual AChEIs were identified with index dates from 1 January 2006 to 31 June 2018, with a 1-year washout period. The study excluded patients with any antimuscarinic use and OAB diagnosis 1 year before the AChEI index date. The primary outcome of interest was the prescription of antimuscarinics within 6 months of the AChEI index date. A Cox proportional hazard model was used to assess the association between individual incident AChEI use and antimuscarinic prescribing cascade after controlling for several covariates. RESULTS: The study included 47,059 older adults with dementia who were incident users of AChEIs. Most of these patients were initiated with donepezil (83.1%), followed by rivastigmine (12.3%) and galantamine (4.6%). Overall, 8.16% of the study cohort had incident OAB diagnosis or antimuscarinic prescription. Antimuscarinics were initiated by 1725 (3.7%) older adults with dementia within 6 months of AChEI prescription, and cascade varied widely across individual agents-donepezil (3.9%), rivastigmine (2.6%), and galantamine (2.9%). Cox proportional hazard analyses revealed that donepezil users had an increased risk of receiving antimuscarinics (adjusted hazard ratio 1.55, 95% confidence interval 1.31-1.83) compared with rivastigmine. The findings were consistent in sensitivity analyses. CONCLUSION: This study found that donepezil use is more likely to lead to antimuscarinic cascade than rivastigmine. Future studies are needed to determine the potential consequences of this cascade in dementia.

Using the Theory of Planned Behavior to Evaluate Factors That Influence PharmD Students' Intention to Attend Lectures.

Objective. To use the theory of planned behavior (TPB) to evaluate the contribution of attitude, subjective norm, and perceived behavioral control in predicting students' intention to attend class lectures in a Doctor of Pharmacy (PharmD) curriculum in which lecture recordings were available. Methods. A survey instrument based on the TPB was developed from focus groups with PharmD students. The survey was then distributed to first through third year students at the conclusion of the 2017-2018 academic school year. Respondents were asked to evaluate their beliefs regarding lecture attendance and their intention to attend lectures during the upcoming fall semester. Predictors of intention were evaluated using descriptive statistics and multiple logistic regression analyses. Results. Responses from 198 of 383 students contained usable data (52% effective response rate). The TPB constructs of attitude and subjective norm were predictors of high intention to attend lectures. Students with a positive attitude towards lecture attendance (eg, believed that purposeful active learning is desirable and occurs during class) were nearly 30% more likely to have high intention to attend lectures. Students with a positive subjective norm (ie, perceived social pressure from professors and classmates to attend lectures) were 66% more likely to have high intention to attend lectures. Perceived behavioral control was not associated with high intention to attend lectures. Conclusion. Interventions aimed at improving students' attitudes and subjective norm may be beneficial in improving students' intention to attend class lectures.

Risk of Mortality Associated With Atypical Antipsychotic use: A National Cohort Study of Older Adults With Depression and Parkinson's Disease.

OBJECTIVES: This study examined the risk of all-cause-mortality in patients with Parkinson's Disease (PD) and comorbid depression using inappropriate atypical antipsychotics (AAPs), based on the 2015 American Geriatrics Society Beers criteria. METHODS: A retrospective analysis of 2007-2010 Minimum Data Set linked Medicare data was conducted using a propensity-matched approach. The cohort included PD patients aged 65 years or older without schizophrenia or bipolar disorder who started AAPs. All patients had a diagnosis of comorbid depression. Risk of 6-month all-cause-mortality was compared across appropriate AAPs (aripiprazole, clozapine, or quetiapine) and inappropriate AAPs (olanzapine, asenapine, brexpiprazole, iloperidone, lurasidone, paliperidone, risperidone, or ziprasidone) using robust Cox regression models involving the matched cohort. RESULTS: All-cause mortality rate was 15.65% in appropriate AAP group (n = 6,038) and 16.91% in inappropriate AAP group (n = 6,038) over 6-month follow-up in the matched cohort. The robust Cox proportional hazards models revealed increased risk of all-cause mortality (hazard ratio [HR] 1.13 [95% confidence interval {CI}: 1.01-1.28)] for patients who used inappropriate compared to appropriate AAPs. Risk of death was also higher for risperidone compared to quetiapine (HR: 1.20 [95% CI: 1.03-1.40]) in sensitivity analysis. However, there was a significant relationship between pneumonia and death in all analyses. The impact of inappropriate AAP use on mortality was not significant when pneumonia was modeled as a mediator. CONCLUSIONS: Inappropriate AAP use is associated with a higher risk of all-cause-mortality in older patients with PD which is mainly mediated by pneumonia. Therefore, inappropriate AAP use should be avoided to improve quality of care in PD.

Use of Atypical Antipsychotics in Long-Term Care Residents with Parkinson's Disease and Comorbid Depression.

PURPOSE: According to the 2015 American Geriatrics Society (AGS) Beers criteria, most antipsychotics are inappropriate in Parkinson's disease (PD) patients due to the risk of worsening Parkinsonian symptoms. This study examined the incidence and predictors of inappropriate antipsychotic use among long-term care residents with PD and comorbid depression. PATIENTS AND METHODS: This retrospective cohort study utilized 2007-2009 Minimum Data Set (MDS) linked to Chronic Condition Warehouse (CCW) Medicare data files involving patients with PD and comorbid depression. Using a 12-month baseline and a 24-month follow-up, the study examined incidence of inappropriate atypical antipsychotics, namely asenapine, brexpiprazole, iloperidone, lurasidone, olanzapine, paliperidone, risperidone, or ziprasidone as specified in the 2015 AGS Beers criteria. Appropriate atypical antipsychotic included aripiprazole, clozapine, or quetiapine. Multivariable logistic regression was used to examine various sociodemographic and clinical factors associated with inappropriate antipsychotic use in PD based on the Andersen Behavioral Model. RESULTS: The incidence of atypical antipsychotic use was 17.50% (13,352/76,294) among PD patients over a 2-year follow-up. The percentage of inappropriate use among atypical antipsychotic users was 36.32%. The likelihood of inappropriate antipsychotic use was higher for patients who had dementia (OR=1.22, 95% CI: 1.12-1.33) or Chronic Obstructive Pulmonary Disease ((OR=1.13, 95% CI: 1.03-1.24). However, patients who were taking levodopa (OR=0.62, 95% CI: 0.57-0.67), dopamine agonists (OR=0.90, 95% CI: 0.82-0.98), Catechol-O-methyltransferase (COMT) inhibitors (OR=0.77, 95% CI: 0.68-0.86), Monoamine Oxidase (MAO) inhibitors type B (OR=0.72, 95% CI: 0.60-0.86), or amantadine (OR=0.84, 95% CI: 0.71-0.98) were less likely to receive inappropriate antipsychotics. CONCLUSION: More than one-third of PD patients used inappropriate antipsychotics among those who were treated with atypical antipsychotic medications. Various socio-demographics and clinical factors were associated with inappropriate antipsychotic use in older patients with PD. Concerted efforts are needed to reduce inappropriate atypical antipsychotic use among PD patients.

Risk of pneumonia associated with atypical antipsychotic use in nursing home residents with Parkinson's disease.

According to the American Geriatrics Society (AGS) Beers criteria, most atypical antipsychotic (AAPs) are inappropriate in patients with Parkinson's disease (PD) due to the risk of worsening Parkinsonian symptoms. This study evaluated the risk of pneumonia associated with inappropriate AAP use in elderly nursing home residents with PD. The study population encompassed older adults aged 65 years or older with a diagnosis of PD and with comorbid depression who started the AAP medication. Appropriate AAPs were defined as aripiprazole, clozapine or quetiapine according to 2015 Beers criteria, and inappropriate AAPs included olanzapine, asenapine, brexpiprazole, iloperidone, lurasidone, paliperidone, risperidone, or ziprasidone. Cox regression analyses involved propensity score-matched users of inappropriate and appropriate AAPs to examine the association between AAP use and risk of pneumonia. The mean age of patients in propensity-matched cohort (n = 12,076) was 82.15 years (SD = 6.97). The pneumonia incidence rates were 37.19 and 45.92 per person-year in appropriate and inappropriate AAP groups, respectively. Multivariable Cox regression analyses revealed increased risk of pneumonia [Hazard Ratio (HR) 1.20 (1.08-1.34)] for nursing home residents who were taking inappropriate compared to those taking appropriate AAP. In sensitivity analyses, the pneumonia risk was 1.28 (1.12-1.47) for risperidone vs. quetiapine and 1.29 (1.06-1.57) for olanzapine vs. quetiapine. The risk of pneumonia was significantly higher for patients with PD who used inappropriate AAP in comparison to appropriate AAP group in all analyses. This investigation warrants further attention regarding safety of atypical antipsychotics in PD.

Care Provision and Prescribing Practices of Physicians Treating Children and Adolescents With ADHD.

OBJECTIVE: Care provision and prescribing practices of physicians treating children with attention-deficit hyperactivity disorder (ADHD) were compared. METHODS: A retrospective cohort study was conducted with the 1995-2010 General Electric Centricity Electronic Medical Record database. The sample included children (≤18 years) with newly diagnosed ADHD (ICD-9-CM code 314.XX) who received a prescription for a stimulant or atomoxetine. Identification of comorbid psychiatric disorders, duration from initial ADHD diagnosis to treatment, prescription of other psychotropic medications, and follow-up care during the ten months after the ADHD treatment initiation were compared across provider type (primary care physicians [PCPs], child psychiatrists, and physicians with an unknown specialty). The associations between provider type and practice variations were further determined by multivariate logistic regression accounting for patient demographic characteristics, region, insurance type, and prior mental health care utilizations. RESULTS: Of the 66,719 children identified, 75.8% were diagnosed by PCPs, 2.6% by child psychiatrists, and 21.6% by physicians whose specialty was unknown. Child psychiatrists were less likely than PCPs to initiate ADHD medication immediately after the diagnosis. However, once the ADHD treatment was initiated, they were more likely to prescribe psychotropic polytherapy even after analyses accounted for the comorbid psychiatric disorders identified. Only one-third of ADHD cases identified by both PCPs and child psychiatrists have met the HEDIS quality measure for ADHD medication-related follow-up visits. CONCLUSIONS: Differences were found by physician type in care of children with ADHD. Additional studies are needed to understand clinical consequences of these differences and the implications for care coordination across provider specialties.

Dispensing inhalers to patients with chronic obstructive pulmonary disease on hospital discharge: Effects on prescription filling and readmission.

PURPOSE: The effects of dispensing inhalers to patients with chronic obstructive pulmonary disease (COPD) on hospital discharge were evaluated. METHODS: Data were collected in 2011-12 for patients with COPD who had hospital orders for the study inhalers (preintervention group) and after implementation of the multidose medication dispensing on discharge (MMDD) service (2013-14) (postintervention group). The primary objective of this study was to assess inhaler adherence and readmission rates before and after MMDD implementation. Adherence was defined as filling the discharge prescription for the multidose inhaler at a Harris Health pharmacy within three days of discharge or having at least seven days of medication left in an inhaler from a previous prescription that was filled or refilled before hospital admission. All patients in the postintervention group were considered adherent, since every patient was given the remainder of his or her multidose inhaler when discharged. RESULTS: Data from 620 patients (412 in the preintervention group, 208 in the postintervention group) were collected. During the preintervention time period, 88 of 412 patients were readmitted within 30 days compared with 18 of 208 patients during the postintervention period (p < 0.001). The intervention was associated with a significant reduction in 30-day readmissions (p = 0.0016) and 60-day readmissions (p = 0.0056). CONCLUSION: A targeted pharmacy program to provide COPD patients being discharged from the hospital with the multidose inhalers they had used during hospitalization was associated with improved medication adherence, as measured by prescription filling behavior, and reduced rates of 30- and 60-day hospital readmissions.

Risk of manic switch associated with antidepressant therapy in pediatric bipolar depression.

OBJECTIVE: The purpose of this study was to assess the risk of manic switch associated with antidepressants in Medicaid-enrolled pediatric patients with bipolar depression. METHODS: This retrospective cohort study involved 2003-2007 Medicaid Analytic eXtract (MAX) data from four geographically diverse states. The study sample included children and adolescents (ages 6-18 years) who had received a diagnosis of bipolar disorder on two or more separate occasions or during a hospital discharge, followed by a diagnosis of depression. According to the pharmacotherapy received by these patients in the 30 days around the index bipolar depression diagnosis, patients were categorized into five mutually exclusive groups. Manic switch was defined as having received a diagnosis of mania within 6 weeks after the initiation of bipolar depression treatment. Relative risks of manic switch between antidepressant monotherapy/polytherapy and their alternatives were assessed using Cox proportional hazards model. The robustness of the conventional Cox proportional hazards model toward possible bias caused by unobserved confounders was tested using instrumental variable analysis, and the uncertainty regarding manic switch definition was tested by altering the duration of follow-up. RESULTS: After applying all the selection criteria, 179 antidepressant monotherapy, 1047 second-generation antipsychotic (SGA) monotherapy, 570 mood stabilizer monotherapy, 445 antidepressant polytherapy, and 1906 SGA-mood stabilizer polytherapy users were identified. In Cox proportional hazard analyses, both antidepressant monotherapy and polytherapy exhibited higher risk of manic switch than their alternatives (antidepressant monotherapy vs. SGA monotherapy, hazard ratio [HR]=2.87 [95% CI: 1.10-7.49]; antidepressant monotherapy vs. mood stabilizer monotherapy, HR=1.41 [95% CI: 0.52-3.80); antidepressant polytherapy vs. SGA-mood stabilizer polytherapy, HR=1.61 [95% CI: 0.90-2.89]). However, only the comparison between antidepressant monotherapy and SGA monotherapy was statistically significant. The instrumental variable analysis did not detect endogeneity of the treatment variables. Extending the follow-up period from 6 weeks to 8 and 12 weeks generated findings consistent with the main analysis. CONCLUSIONS: Study findings indicated a higher risk of manic switch associated with antidepressant monotherapy than with SGA monotherapy in pediatric patients with bipolar depression. The finding supported the clinical practice of cautious prescribing of antidepressants for brief periods.

The utilization of psychopharmacological treatment and medication adherence among Medicaid enrolled children and adolescents with bipolar depression.

BACKGROUND: To examine the psychotropic medication utilization and compare adherence to treatment regimens in pediatric bipolar depression patients. METHODS: 2003-2007 MAX data from four geographically diverse states were used. According to the regimen received by the patients (6-18 years) in the first month after the index bipolar depression diagnosis, patients were categorized into six mutually exclusive groups. The month to month change of treatment regimen in each group was then assessed during the 6 month post-index bipolar depression diagnosis. Adherence to each regimen was measured as continuation of the initial regimen, switch to a new regimen, augmentation with medication from a different therapeutic category, and discontinuation of all pharmacotherapies. Repeated measure analysis was conducted to compare the trend of each adherence measure across the study groups. RESULTS: Of the 5,460 subjects identified, 15.39% received antipsychotic monotherapy, 9.43% received mood stabilizer monotherapy, 5.77% received antidepressant monotherapy, 26.48% received mood stabilizer-antipsychotic polytherapy, 22.51% received antidepressant polytherapy, and 19.89% received antipsychotic-mood stabilizer-antidepressant polytherapy. At the end of the follow-up period, over 50% of the 1st month polytherapy users and less than 50% of the monotherapy users were continuing their initial regimen. Repeated measure analysis using antipsychotic monotherapy as the reference group suggested differences in trend slopes (p<0.05). LIMITATIONS: In absence of structured clinical evaluation, bipolar disorder diagnoses cannot be ascertained in this study. CONCLUSIONS: Bipolar depression patients were predominantly treated with combinations of psychotropic drugs. Potentially questionable practice, such as antidepressant monotherapy was used only in a small fraction of patients. Combination regimens had better adherence as compared to monotherapies.

The definition and prevalence of pediatric psychotropic polypharmacy.

OBJECTIVES: Using increasingly stringent criteria, this study evaluated the prevalence of psychotropic polypharmacy among children on the basis of duration of overlap between two or more psychotropic medications. METHODS: The prevalence of psychotropic polypharmacy was defined as receiving ≥ 14 days, ≥ 30 days, ≥ 60 days, and ≥ 90 days of overlapping psychotropic prescription fills. Descriptive analysis was used to compare the prevalence findings on the basis of multistate Medicaid data involving children six to 18 years of age. A sensitivity analysis was also conducted to explore the extent to which the cross-sectional operational definitions of polypharmacy used in the published literature identified patients who were prescribed psychotropic combinations on a long-term basis. RESULTS: The analysis revealed that 282,910 children had at least one psychotropic prescription fill in 2005. Of these patients, 28.8% received psychotropic combinations for at least 14 consecutive days. The observed rate of polypharmacy dropped to 27.2% with 30 days of overlap and to 20.9% with 60 days of overlap. Using a 60-day overlap in psychotropic drugs as a cutoff between short-term and long-term polypharmacy, analyses showed that 14%-46% of patients identified by cross-sectional definitions as receiving polypharmacy had likely received combination treatment on a temporary rather than on a long-term basis. In addition, cross-sectional definitions failed to identify 18%-44% of patients classified as receiving long-term polypharmacy (≥ 60-day overlap). CONCLUSIONS: The observed rate of polypharmacy dropped with increasingly stringent operational definitions for polypharmacy. The findings suggest that considerable differences arise when comparing rates of polypharmacy across studies with inconsistent operational definitions.

Prevalence and predictors of anticholinergic medication use in elderly nursing home residents with dementia: analysis of data from the 2004 National Nursing Home Survey.

BACKGROUND: Medications with anticholinergic properties are frequently used in the elderly population. However, evidence suggests that these medications are associated with significant adverse effects and may lead to worsening of cognitive impairment, particularly in elderly patients with dementia. OBJECTIVE: To examine the utilization of anticholinergic medications and factors associated with anticholinergic medication use in elderly nursing home patients with dementia. METHODS: The study examined anticholinergic medication utilization for patients aged ≥65 years with dementia, using the 2004 US National Nursing Home Survey (NNHS) data. Anticholinergic drugs were identified using the Anticholinergic Drug Scale (ADS), which classifies anticholinergic drugs into four levels in increasing order of their anticholinergic activity. Descriptive analysis was conducted using sampling weights to determine the prevalence of anticholinergic medication use. Multiple logistic regression within the conceptual framework of the Andersen Behavioral Model was used to examine the factors associated with anticholinergic medication use in the study population. Use of medications with marked anticholinergic activities (ADS level 2 or 3) was the dependent variable, and independent variables were the various predisposing, enabling and need factors. RESULTS: According to the 2004 NNHS, 509,931 (95% CI 490,160, 529,702) or 73.62% (95% CI 72.23, 75.00) of elderly patients with dementia used anticholinergic medications. The highest prevalence of anticholinergic medication use among elderly patients with dementia was seen for level-1 medications (67.96%; 95% CI 66.51, 69.41), and 21.27% (95% CI 19.93, 22.60) used ADS level-2 or level-3 medications. Multivariate regression analysis showed that the predisposing factor of age was negatively associated with the use of medications with marked anticholinergic activities (ADS level 2 or 3) and the enabling factor of Medicaid as the source of payment increased the likelihood of receiving these higher-level anticholinergics. Among the need factors, dependence in decision-making ability and behavioural symptoms decreased the likelihood of receiving higher-level anticholinergics, whereas factors such as total number of medications, depressed mood indicators and diagnoses of schizophrenia, anxiety and Parkinson's disease increased the likelihood of use of such medications. CONCLUSIONS: Over one in five elderly nursing home residents with dementia used medications with marked anticholinergic activities. The study findings suggest the need to optimize the use of anticholinergic medications in vulnerable patients with dementia given the potentially severe adverse cognitive effects of these agents.

Extent of functional impairment in children and adolescents with depression.

OBJECTIVE: Pediatric depression is often associated with clinically significant distress or impairment in school, home and social activities. However, very little is known about the extent of functional impairment in children with depression based on national level data. This study examined the extent of functional impairment in children and adolescents aged 5 to 17 years with depression based on 2005-2006 Medical Expenditure Panel Survey (MEPS) data. RESEARCH DESIGN AND METHODS: This study involved retrospective cross-sectional analysis of 2005-2006 MEPS data. Functional impairment in children was assessed using the parent-reported Columbia Impairment Scale (CIS). The CIS is a 13 item, lay-interviewer-administered global impairment scale. The analysis focused on children with depression. Functional impairment was ascertained using the mean summated scores of the CIS after conducting psychometric analysis. The Wilson and Cleary model was used to examine the factors associated with functional impairment in children and adolescents. RESULTS: Analysis of the CIS revealed that Cronbach's alpha of the parent-reported CIS was 0.90 with item-to-total correlations ranging from 0.51 to 0.77. The mean summated CIS score in children and adolescents with depression (CIS, 19.88) was higher (p < 0.05) than those without depression (CIS, 6.09). Multivariate linear regression revealed the interaction between age and depression was significant (p < 0.05) and therefore stratified regression analysis was performed by age. In both age groups, the diagnosis of depression was strongly associated (p < 0.01) with functional impairment (+7 units in 5-11 years, +11 units in 12-17 years). The presence of developmental, respiratory tract, attention deficit, and anxiety disorders also increased functional impairment in children and adolescents (p < 0.05). Family factors such as parents' psychiatric illness, their education and their living arrangement significantly contributed (p < 0.05) to impairment in children and adolescents. CONCLUSIONS: Functional impairment is significant in pediatric depression and understanding of personal and family factors can play an important role in the assessment, management and treatment of depression. The limitations of the study include cross-sectional study design and reliance on parent-reported data on medical condition and impairment.

Use of antipsychotics among elderly nursing home residents with dementia in the US: an analysis of National Survey Data.

BACKGROUND: Atypical antipsychotic agents are increasingly being used for the treatment of behavioural and psychological symptoms of dementia. However, recent data suggest that the risk of adverse effects may offset the benefits of atypical agents in patients with dementia. OBJECTIVES: To examine utilization of antipsychotic medications and the factors associated with use of atypical antipsychotics among elderly nursing home residents with dementia. METHODS: The study involved the analysis of prescription and resident files of a nationally representative sample of residents from the 2004 National Nursing Home Survey (NNHS). The study sample included an unweighted sample of 6103 elderly nursing home residents aged > or =65 years with dementia. The analysis focused on the use of six atypical antipsychotic agents and 11 typical agents. Descriptive weighted analysis was performed to examine the antipsychotic prevalence patterns in elderly nursing home residents with dementia. Multiple logistic regression analysis within the conceptual framework of Andersen's Behavioural Model was used to examine the predisposing, enabling and need characteristics associated with use of atypical antipsychotics. RESULTS: According to the 2004 NNHS, the overall prevalence of dementia among elderly nursing home residents was 52.58%. Most of the elderly with dementia were female (77%), aged > or =85 years (56%), non-Hispanic (97%) and White (88%). Antipsychotic medications were taken by 32.88% of elderly patients with dementia. More elderly residents received atypical agents (31.63%) than typical agents (1.75%). Among the predisposing characteristics, the odds of receiving atypical antipsychotics were lower for females than males. The enabling factor facility bed capacity was significantly associated with use of atypical antipsychotics. Among the need characteristics, the likelihood of receiving atypical antipsychotic agents increased with dependence in decision-making ability, indicators of depressed mood and behavioural symptoms. The likelihood of receiving atypical antipsychotic agents decreased with increasing dependence for out-of-bed mobility and increased total activities of daily living. The odds of receiving atypical antipsychotic treatment increased with the diagnosis of schizophrenia, bipolar mania and anxiety among dementia patients. CONCLUSION: Nearly one-third of elderly nursing home residents with dementia received antipsychotic medications, mainly atypical agents. Predisposing, enabling and need factors influenced the use of atypical agents in dementia patients. These findings suggest a need to optimize use of atypical antipsychotics in elderly dementia patients in nursing homes in the light of recent efficacy and safety data.

Outcomes of patients with prostate cancer receiving zoledronic acid or pamidronate for prevention of skeletal-related events.

STUDY OBJECTIVE: To determine the relative effectiveness of two bisphosphonates--pamidronate and zoledronic acid--for preventing skeletal-related events (SREs) in patients with prostate cancer metastatic to bone. DESIGN: Retrospective cohort study. SETTING: Large, tertiary care cancer center. PATIENTS: One hundred thirty-seven patients with a diagnosis of prostate cancer who received either pamidronate or zoledronic acid between January 1, 1998, and December 31, 2004, were identified in the electronic medical records; 24 of these patients met all prespecified eligibility criteria, and 105 patients met relaxed eligibility criteria. MEASUREMENTS AND MAIN RESULTS: Using a binary logistic regression model, we explored the effect of the bisphosphonate received on development of an SRE. Whether the patient was receiving chemotherapy as of the date of first receipt of a study drug, the number of bisphosphonate doses received, time since the diagnosis of prostate cancer, and the number of previous SREs were included as covariates. The odds ratio for developing an SRE after receiving zoledronic acid was 0.80 (95% confidence interval 0.08-7.50) compared with the reference group that received pamidronate. This difference did not reach statistical significance (p=0.84). Because of the limited number of patients who met all prespecified eligibility criteria, various post hoc analyses were performed in the 105 patients with use of relaxed eligibility criteria. None provided definitive evidence of the superiority of one agent versus the other. CONCLUSION: No definitive evidence of a difference in the efficacy for preventing the development of an SRE was found between pamidronate and zoledronic acid, although a smaller-than-expected sample size impairs the interpretability of this finding. In the absence of additional research, it seems reasonable to assume that no clinically important difference exists between the two agents.