The objectives of the study were as follows: to examine the national trend of pediatric atypical antipsychotic (AAP) use in the United States; to identify primary mental disorders associated with ...AAPs; to estimate the strength of independent associations between patient/provider characteristics and AAP use. Data are from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. First, average AAP prescription rates among 4 and 18-year-old patients between 1993 and 2010 were estimated. Second, data from 2007 to 2010 were combined and analyzed to identify primary mental disorders related to AAP prescription. Third, a multivariate logistic regression model was developed having the presence of AAP prescription as the dependent variable and patient/provider characteristics as explanatory variables. Adjusted odds ratios (AORs) with associated 95% confidence intervals (CIs) were estimated. Outpatient visits including an AAP prescription among 4 to 18-year-old patients significantly increased between 1993 and 2010 in the United States, and over 65% of those visits did not have diagnoses for US Food and Drug Administration-approved AAP indications. During 2007 to 2010, the most common mental disorder was attention-deficit hyperactivity disorder, accounting for 24% of total pediatric AAP visits. Among visits with attention-deficit hyperactivity disorder diagnosis, those with Medicaid as payer (AOR 1.66, 95% CI 1.01-2.75), comorbid mental disorders (e.g., psychoses AOR 3.34, 95% CI 1.35-8.26), and multiple prescriptions (4 or more prescriptions AOR 4.48, 95% CI 2.08-9.64) were more likely to have an AAP prescription. The off-label use of AAPs in children and adolescents is prevalent in the United States. Our study raises questions about the potential misuse of AAPs in the population.
Given the controversy around the effectiveness of opioid treatment for chronic pain and the lack of detailed guidance for prescribing opioids in older adults, the objectives of this study were to ...estimate the trajectories and predictors of opioid use in older adults.
Data were extracted from the National Alzheimer's Coordinating Center (2005-2017). Group-based trajectory modeling was used to identify the patterns of opioid use (any or strong) among participants age 65+. We used multivariable logistic regression with backward selection to evaluate demographics and comorbidities as potential predictors of trajectory membership.
Among 13,059 participants, four trajectories were identified for the use of both any opioids and strong opioids (minimal-users, incident chronic-users, discontinuing-users, and prevalent chronic-users). For any opioids, female sex (adjusted odds ratio = 1.23; 95% confidence interval = 1.03-1.46), black vs. white (1.47; 1.18-1.82), year of education (0.96; 0.94-0.99), type of residence (independent group vs. private: 1.77; 1.38-2.26, care facility vs. private: 1.89; 1.20-2.97), hypertension (1.44; 1.20-1.72), cardiovascular disease (1.30; 1.09-1.55), urinary incontinence (1.45; 1.19-1.78), dementia (0.73; 0.57-0.92), number of medications (1 to 4 vs. none: 0.48; 0.36-0.64, 5 or more vs. none: 0.67; 0.50-0.88), and antidepressant agent (1.38; 1.14-1.67) were associated with incident chronic-use vs. non-use. For strong opioids, female sex (1.27; 1.04-1.56), type of residence (independent group vs. private: 1.90; 1.43-2.53, care facility vs. private: 2.37; 1.44-3.90), current smoking (1.68; 1.09-2.60), hypertension (1.49; 1.21-1.83), urinary incontinence (1.45; 1.14-1.84), dementia (0.73; 0.55-0.97), number of medications (1 to 4 vs. none: 0.46; 0.32-0.65, 5 or more vs. none: 0.59; 0.42-0.83), and antidepressant agent (1.55; 1.24-1.93) were associated with incident chronic-use vs. non-use.
Given that chronic opioid use was more prevalent in participants who were more vulnerable (i.e., older age, with multiple comorbidities, and polypharmacy), further studies should evaluate the safety and efficacy of using opioids in this population.
Gabapentin is increasingly prescribed to older adults, which raises concerns about its potential to cause neurocognitive changes. Therefore, we aimed to examine the association of gabapentin use with ...neurocognitive changes (i.e., cognitive decline, functional status decline, and motor function change) in older adults.
We conducted a retrospective cohort study using the National Alzheimer's Coordinating Center Uniform Data Set (UDS; September 2005-March 2021 data freeze). From the eligible sample (≥age 65 years), we identified cognitively normal new-users of gabapentin and the visit they initiated gabapentin (i.e., index visit). Initiators were matched to randomly selected nonusers on year of UDS enrollment and visit number from enrollment to index. Cognitive decline was defined as any increase in the Clinical Dementia Rating global score (CDRGLOB) and as a 1-point increase in CDR sum of boxes (CDR-SB). Functional status decline was defined as a 3-point increase in the sum of the Functional Activities Questionnaire (FAQ) and as 0.3-point increase in mean FAQ. Decline in motor function was defined as new clinician reports of gait disorder, falls, and slowness. To mitigate confounding and selection bias, we used joint stabilized inverse probability of treatment weights and stabilized inverse probability of censoring weights. All analyses were conducted comparing index to index+1 and index+2 visits.
From the eligible UDS participants (N = 23,059), we included 480 initiators (mean age SD: 78.7 6.9; male 34.4%); 4,320 nonusers (78.3 7.0; 34.4%). Gabapentin initiation was significantly associated with cognitive/functional status decline: worsening CDRGLOB at index+1 visit (odds ratio 95% confidence interval: 1.55 1.07, 2.25); CDR-SB at index+1 visit (1.94 1.22, 3.09); and mean of FAQ at index+2 visit (1.78 1.12, 2.83). After excluding initiators with extant motor dysfunction (n = 21), we identified 459 initiators (78.7 6.9; 34.0%) and 4,131 nonusers (78.2 6.9; 34.7%); in this sample, gabapentin initiation was associated with increased falls at the index+2 visit (2.51 1.19, 5.31).
Gabapentin initiation was significantly associated with deleterious neurocognitive changes among older adults with initially normal cognition. Further studies are needed to examine the risk/benefit of prescribing gabapentin in older adults.
This study aimed to examine gabapentin utilization trends among older adults with different cognitive statuses and investigate concurrent medication use of potentially inappropriate medications. Data ...were extracted from the National Alzheimer's Coordinating Center Uniform Data Set (2006–2019). We estimated the yearly prevalence of gabapentin use, both overall and within subgroups defined by cognitive status (normal, mild cognitive impairment and dementia) and demographics (age and sex) for participants aged 65+. Additionally, we assessed the prevalence of concurrent use of gabapentin with opioids, combined opioids and benzodiazepine, antidepressant and antipsychotic. From 35 205 eligible older adults (mean age SD: 75.7 7.0; male: 43.1%), gabapentin use increased from 2006 to 2019 in both overall and every participant subgroup. About 10%–30% of gabapentin users reported to concurrently use opioids, and the concurrent use of gabapentin, opioid and benzodiazepine was up to 7.5% throughout the study period. The frequency of concurrent use with antipsychotics or antidepressants was higher in participants with dementia than those with normal cognition or those who were mildly cognitively impaired. Given increasing use among older adults, rigorous studies are needed to examine the safety of gabapentin in this population.
Objective
To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI).
Methods
Data were drawn from a large autopsy series (N = 1,337) of ...individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.
Results
Mean follow‐up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical diagnosis of MCI. In terms of non‐AD pathologies, both primary age‐related tauopathy (p < 0.05) and brain arteriolosclerosis pathology (p < 0.001) were more severe in MCI than cognitively intact controls. Among the group that remained MCI until death, mixed AD neuropathologic changes (ADNC; ≥1 comorbid pathology) were more frequent than “pure” ADNC pathology (55% vs 22%); suspected non‐Alzheimer pathology comprised the remaining 22% of cases. A majority (74%) of subjects who died with MCI were without “high”‐level ADNC, Lewy body disease, or hippocampal sclerosis pathologies; this group was enriched in cerebrovascular pathologies. Subjects who died with dementia and were without severe neurodegenerative pathologies tended to have cerebrovascular pathology and carry the MCI diagnosis for a longer interval.
Interpretation
MCI diagnosis usually was associated with comorbid neuropathologies; less than one‐quarter of MCI cases showed “pure” AD at autopsy. Ann Neurol 2017;81:549–559
The diagnostic accuracy of computer detection programs has been reported to be comparable to that of specialists and expert readers, but no computer detection programs have been validated in an ...independent cohort using an internationally recognized diabetic retinopathy (DR) standard.
To determine the sensitivity and specificity of the Iowa Detection Program (IDP) to detect referable diabetic retinopathy (RDR).
In primary care DR clinics in France, from January 1, 2005, through December 31, 2010, patients were photographed consecutively, and retinal color images were graded for retinopathy severity according to the International Clinical Diabetic Retinopathy scale and macular edema by 3 masked independent retinal specialists and regraded with adjudication until consensus. The IDP analyzed the same images at a predetermined and fixed set point. We defined RDR as more than mild nonproliferative retinopathy and/or macular edema.
A total of 874 people with diabetes at risk for DR.
Sensitivity and specificity of the IDP to detect RDR, area under the receiver operating characteristic curve, sensitivity and specificity of the retinal specialists' readings, and mean interobserver difference (κ).
The RDR prevalence was 21.7% (95% CI, 19.0%-24.5%). The IDP sensitivity was 96.8% (95% CI, 94.4%-99.3%) and specificity was 59.4% (95% CI, 55.7%-63.0%), corresponding to 6 of 874 false-negative results (none met treatment criteria). The area under the receiver operating characteristic curve was 0.937 (95% CI, 0.916-0.959). Before adjudication and consensus, the sensitivity/specificity of the retinal specialists were 0.80/0.98, 0.71/1.00, and 0.91/0.95, and the mean intergrader κ was 0.822.
The IDP has high sensitivity and specificity to detect RDR. Computer analysis of retinal photographs for DR and automated detection of RDR can be implemented safely into the DR screening pipeline, potentially improving access to screening and health care productivity and reducing visual loss through early treatment.
Abstract
Background
Treatment recommendations for patients with neuroendocrine tumors (NETs) include the use of octreotide long-acting release (LAR) for long-term therapy and immediate-release (IR) ...as rescue therapy to control the breakthrough symptoms of carcinoid syndrome (CS). High doses of LAR are commonly used in clinical practice. This study aimed to evaluate the real-world utilization of LAR and preceding IR use at the prescription and patient levels.
Methods
We used an administrative claims database (2009-2018) containing privately insured enrollees. We calculated the normalized LAR dose from pharmacy claims and the initial mean IR daily dose at the prescription level. At the patient level, we conducted a retrospective cohort study that included patients continuously enrolled with ≥1 pharmacy claim of LAR and evaluated the frequency and the clinical reason for dose escalation of LAR. The definition of the above-label maximum dose of LAR was ≥30 mg/4 weeks.
Results
Nineteen percent of LAR prescriptions had an above-label maximum dose. Only 7% of LAR prescriptions had preceding IR use. There were 386 patients with NETs or CS vs. 570 with an unknown diagnosis. Comparing patients with NETs or CS to those with an unknown diagnosis, 22.3% vs. 11.0 % experienced dose escalations and 29.0% vs. 26.6% had IR use before dose escalation, respectively. LAR dose escalation occurred in 50.9% vs. 39.2% for symptom control, 12.3% vs. 7.1% for tumor progression control, and 16.6% vs. 6.0% for both reasons in NETs/CS and unknown groups, respectively.
Conclusion
Octreotide LAR dosing above the label-maximum dose is common and IR rescue dosing appears to be underutilized.
Treatment recommendations for patients with neuroendocrine tumors (NETs) include the use of octreotide long-acting release (LAR) for long-term therapy and immediate-release (IR) as rescue therapy to control the breakthrough symptoms of carcinoid syndrome. This article evaluates the real-world utilization of LAR and preceding IR use at the prescription and patient levels.
Polypharmacy and inappropriate medications may be a modifiable risk factor for Alzheimer's Disease and Related Dementias (ADRD). Medication therapy management (MTM) interventions may mitigate ...medication-induced cognitive dysfunction and delay onset of symptomatic impairment. The objective of the current study is to describe an MTM protocol for a patient-centered team intervention (pharmacist and non-pharmacist clinician) in a randomized controlled trial (RCT) directed at delaying the symptomatic onset of ADRD.
Community dwelling adults 65 + years, non-demented, using ≥ 1 potentially inappropriate medications (PIM) were enrolled in an RCT to evaluate the effect of an MTM intervention on improving medication appropriateness and cognition (NCT02849639). The MTM intervention involved a three-step process: (1) pharmacist identified potential medication-related problems (MRPs) and made initial recommendations for prescribed and over-the-counter medications, vitamins, and supplements; (2) study team reviewed all initial recommendations together with the participants, allowing for revisions prior to the finalized recommendations; (3) participant responses to final recommendations were recorded. Here, we describe initial recommendations, changes during team engagement, and participant responses to final recommendations.
Among the 90 participants, a mean 6.7 ± 3.6 MRPs per participant were reported. Of the 259 initial MTM recommendations made for the treatment group participants (N = 46), 40% percent underwent revisions in the second step. Participants reported willingness to adopt 46% of final recommendations and expressed need for additional primary care input in response to 38% of final recommendations. Willingness to adopt final recommendations was highest when therapeutic switches were offered and/or with anticholinergic medications.
The evaluation of modifications to MTM recommendations demonstrated that pharmacists' initial MTM recommendations often changed following the participation in the multidisciplinary decision-making process that incorporated patient preferences. The team was encouraged to see a correlation between engaging patients and a positive overall response towards participant acceptance of final MTM recommendations.
Study registration number: clinicaltrial.gov NCT02849639 registered on 29/07/2016.
Potentially inappropriate anticholinergic medications (including over-the-counter products), polypharmacy, and the existence of communication barriers among members of the interprofessional team ...frequently contribute to clinical complexity in older adults. We present the case of a frail 86-year old female from the perspective of a community pharmacist managing outpatient medications and transitions of care. CD's past medical history is significant for dementia, multiple falls, recurrent urinary tract infections, depression, cardiac arrhythmia, macular degeneration, chronic pain, depression, and cerebrovascular disease.
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