Acceptability of patient-centered, multi-disciplinary medication therapy management recommendations: results from the INCREASE randomized study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: Study registration number: clinicaltrial.gov NCT02849639 registered on 29/07/2016.

Computing antimicrobial use/antimicrobial resistance ratios: A novel way to assess inpatient antimicrobial utilization using current National Healthcare Safety Network metrics.

BACKGROUND: Current methods for benchmarking inpatient antimicrobial use (AU) could benefit from combining AU with antimicrobial resistance (AR) information to provide metrics benchmarked to microbiological data; this may yield more instructive and better risk-adjusted measurements than AU and AR in isolation. METHODS: In this retrospective single-center study, we computed facility-wide AU/AR ratios from 2019 to 2020 for specific antimicrobial agents and corresponding AR events, and compared median monthly AU/AR ratios between March 2019 through December 2019 (pre-COVID period) and March 2020 through December 2020 (COVID period). Aggregate AU was expressed as a ratio to aggregate AR events for antimicrobials that typically have activity against the AR organism and are frequently used to treat the AR organism in clinical practice. We also computed AU/AR ratios in our surgical intensive care unit in the pre-COVID period. RESULTS: High-median facility-wide monthly AU/AR ratios were observed for intravenous vancomycin/methicillin-resistant Staphylococcus aureus, with 130.0 in the pre-COVID period and 121.3 in the COVID period (p =.520). Decreases in facility-wide median monthly AU/AR ratios were observed between periods for meropenem/ESBL Enterobacterales (20.9 vs. 7.9, p < .001), linezolid/vancomycin-resistant Enterococcus (48.5 vs. 15.8, p =.004), and daptomycin/vancomycin-resistant Enterococcus (32.2 vs. 4.8, p = .002). Increases in facility-wide median monthly AU/AR ratios were observed between periods for ceftazidime-avibactam/carbapenem-resistant Enterobacterales (0.0 vs. 3.2, p = .020) and ceftazidime-avibactam/multidrug-resistant Pseudomonas aeruginosa (0.0 vs. 4.0, p = .017). The AU/AR ratio for intravenous vancomycin/methicillin-resistant S. aureus in the surgical intensive care unit was 191.5 in the pre-COVID period. CONCLUSIONS: AU/AR ratios may be used to supplement current AU and AR metrics. Future directions should include the development of more AU metrics benchmarked to microbiological information. AU metrics more specific to transplant infectious diseases should be developed.

Internet-Based Cognitive Behavioral Therapy for Insomnia in Appalachian Women: A Pilot Study.

OBJECTIVE/BACKGROUND: Appalachian women are disproportionately affected by insufficient sleep but live in a healthcare shortage area with prevalent prescription drug abuse. A self-administered, non-pharmacologic intervention such as Internet-based cognitive behavioral therapy for insomnia (CBT-I) may be ideal in this population, but psycho-social characteristics (e.g., high depression rates) and cultural norms (e.g., suspicion of technology) necessitate a pilot study. We evaluated the effectiveness of Sleep Healthy Using the Internet (SHUTi) on insomnia severity, sleep quality, perceived stress, depression symptoms, and sleep aid use in Appalachian women ages 45 +. PARTICIPANTS: Forty-six women enrolled; 38 completed the six-week intervention in 2018 (mean age 55 years). METHODS: We employed a single group, pre/post-test, mixed-methods design. Participants completed an online survey and a qualitative interview pre- and post-intervention. Quantitative data were analyzed using one-way repeated measures ANOVA or generalized estimating equations. Interviews were qualitatively analyzed using a multi-stage coding process. RESULTS: Positive and statistically significant (p < .01) improvements were observed on mean scores for the Insomnia Severity Index (15.1 to 6.5), the Pittsburgh Sleep Quality Index (12.1 to 8.5), the Perceived Stress Scale (20 to 14.6), and the Center for Epidemiologic Studies Depression Scale Revised (9.8 to 5.2). The odds of reporting sleep medication use post-intervention were significantly lower than pre-intervention (OR 0.28 [95% CI 0.11-0.74]). Interviews highlighted most and least helpful intervention components and suggested that participants benefitted from SHUTi. CONCLUSIONS: Internet-based CBT-I may be a useful, non-pharmacologic treatment that reduces insomnia severity, perceived stress, depression symptoms, and sleep aid use in middle-aged Appalachian women.

Comparative antimicrobial use in coronavirus disease 2019 (COVID-19) and non-COVID-19 inpatients from 2019 to 2020: A multicenter ecological study.

OBJECTIVE: We sought to determine whether increased antimicrobial use (AU) at the onset of the coronavirus disease 2019 (COVID-19) pandemic was driven by greater AU in COVID-19 patients only, or whether AU also increased in non-COVID-19 patients. DESIGN: In this retrospective observational ecological study from 2019 to 2020, we stratified inpatients by COVID-19 status and determined relative percentage differences in median monthly AU in COVID-19 patients versus non-COVID-19 patients during the COVID-19 period (March-December 2020) and the pre-COVID-19 period (March-December 2019). We also determined relative percentage differences in median monthly AU in non-COVID-19 patients during the COVID-19 period versus the pre-COVID-19 period. Statistical significance was assessed using Wilcoxon signed-rank tests. SETTING: The study was conducted in 3 acute-care hospitals in Chicago, Illinois. PATIENTS: Hospitalized patients. RESULTS: Facility-wide AU for broad-spectrum antibacterial agents predominantly used for hospital-onset infections was significantly greater in COVID-19 patients versus non-COVID-19 patients during the COVID-19 period (with relative increases of 73%, 66%, and 91% for hospitals A, B, and C, respectively), and during the pre-COVID-19 period (with relative increases of 52%, 64%, and 66% for hospitals A, B, and C, respectively). In contrast, facility-wide AU for all antibacterial agents was significantly lower in non-COVID-19 patients during the COVID-19 period versus the pre-COVID-19 period (with relative decreases of 8%, 7%, and 8% in hospitals A, B, and C, respectively). CONCLUSIONS: AU for broad-spectrum antimicrobials was greater in COVID-19 patients compared to non-COVID-19 patients at the onset of the pandemic. AU for all antibacterial agents in non-COVID-19 patients decreased in the COVID-19 period compared to the pre-COVID-19 period.

Improvement in Post-traumatic Stress Symptoms Following an Internet-based Cognitive-Behavioral Intervention for Insomnia: An Open Trial among Rural Appalachian Women.

Appalachian women face significant health disparities and have limited access to health care. Mental health conditions and treatment-seeking are stigmatized in Appalachian communities. Appalachian women may benefit from web-based interventions targeting less stigmatized health complaints (e.g., insomnia), while simultaneously yielding benefit in associated mental health conditions including symptoms of post-traumatic stress disorder (PTSD). In this study, 37 trauma-exposed adult women aged 45 and older from rural Appalachian Kentucky completed a six-session online self-administered cognitive behavioral therapy for insomnia (CBT-I) intervention and completed measures of PTSD symptoms, insomnia, and depression at pre- and post-treatment. Participants reported a significant reduction in PTSD symptoms from pre- to post-intervention, and this remained significant after adjusting for severity of insomnia and depression pre-treatment. Pending replication in a randomized controlled trial, web-based CBT-I may offer an adjunctive mental health treatment option that circumvents cultural stigmas and reduces PTSD symptoms for trauma-exposed Appalachian women.

Hospital-acquired coronavirus disease 2019 (COVID-19) among patients of two acute-care hospitals: Implications for surveillance.

OBJECTIVES: We quantified hospital-acquired coronavirus disease 2019 (COVID-19) during the early phases of the pandemic, and we evaluated solely temporal determinations of hospital acquisition. DESIGN: Retrospective observational study during early phases of the COVID-19 pandemic, March 1-November 30, 2020. We identified laboratory-detected severe acute respiratory coronavirus virus 2 (SARS-CoV-2) from 30 days before admission through discharge. All cases detected after hospital day 5 were categorized by chart review as community or unlikely hospital-acquired cases, or possible or probable hospital-acquired cases. SETTING: The study was conducted in 2 acute-care hospitals in Chicago, Illinois. PATIENTS: The study included all hospitalized patients including an inpatient rehabilitation unit. INTERVENTIONS: Each hospital implemented infection-control precautions soon after identifying COVID-19 cases, including patient and staff cohort protocols, universal masking, and restricted visitation policies. RESULTS: Among 2,667 patients with SARS-CoV-2, detection before hospital day 6 was most common (n = 2,612; 98%); detection during hospital days 6-14 was uncommon (n = 43; 1.6%); and detection after hospital day 14 was rare (n = 16; 0.6%). By chart review, most cases after day 5 were categorized as community acquired, usually because SARS-CoV-2 had been detected at a prior healthcare facility (68% of cases on days 6-14 and 53% of cases after day 14). The incidence rates of possible and probable hospital-acquired cases per 10,000 patient days were similar for ICU- and non-ICU patients at hospital A (1.2 vs 1.3 difference, 0.1; 95% CI, -2.8 to 3.0) and hospital B (2.8 vs 1.2 difference, 1.6; 95% CI, -0.1 to 4.0). CONCLUSIONS: Most patients were protected by early and sustained application of infection-control precautions modified to reduce SARS-CoV-2 transmission. Using solely temporal criteria to discriminate hospital versus community acquisition would have misclassified many "late onset" SARS-CoV-2-positive cases.

Potentially Inappropriate Medication Use in Older Adults with Alzheimer's Disease and Related Dementias Living in the Community: A Cross-Sectional Analysis.

BACKGROUND: With the older adult population in the USA increasing, so is the population of those with Alzheimer's disease and related dementias (ADRD). Older adults are vulnerable to the effects of potentially inappropriate medications as established by the Beers Criteria; however, some medications continue to be prescribed against recommendations. OBJECTIVES: Our objectives were to describe potentially inappropriate medication (PIM) use linked to cognitive impairment or decline (referred to as Cog-PIM) in older adults with and without ADRD and to investigate whether the odds of Cog-PIM report differ by ADRD status in ambulatory care (i.e., outpatient care) in the USA. METHODS: A cross-sectional analysis was performed using a nationally representative sample of non-perioperative, office-based ambulatory care visits by adults aged ≥ 65 years in 2016 (n = 218,182,131). Data were collected from the National Ambulatory Medical Care Survey. Cog-PIMs were identified as defined in the 2015 Beers Criteria recommendations for medications that may be potentially inappropriate in older adults with cognitive impairment or dementia. ADRD status was determined by clinician report using free text, the ADRD flag, or the presence of a diagnosis code indicating dementia. Multivariable logistic regressions were used to estimate the odds of Cog-PIM use overall and by medication class. RESULTS: In 2016, 2.1% (n = 4,651,563) of outpatient visits were made by older adults with ADRD, 33.2% of which reported at least one Cog-PIM. Anticholinergic Cog-PIMs were noted in 20.5% of ADRD visits compared with 8.1% of non-ADRD visits. Antipsychotic PIMs were noted in 15.5% of ADRD visits compared with 0.8% of non-ADRD visits. Benzodiazepine and non-benzodiazepine receptor agonist hypnotic (Z drug) Cog-PIMs were reported in 10.9% of ADRD visits and 10.7% of non-ADRD visits. ADRD status was a significant predictor of Cog-PIM report overall (adjusted odds ratio [aOR] 2.74 [95% confidence interval {CI} 1.20-6.27]) and for anticholinergics and antipsychotics specifically (aOR 3.35 [95% CI 1.24-9.03] and aOR 22.80 [95% CI 5.80-89.50], respectively). CONCLUSION: This study demonstrated a high prevalence of Cog-PIM use and increased odds of Cog-PIM use in older adults with ADRD. Future work should investigate opportunities in the ambulatory care setting for safer prescribing and de-escalation of Cog-PIMs.

An investigation of new medications initiation during ambulatory care visits in patients with dementia.

Background: There is currently insufficient data describing how new medications are provided to older adult ambulatory patients with dementia in the United States (US). Objectives: To describe characteristics of ambulatory care visits for adults ≥65 years old and investigate differences in prescribing of new medications between patients with and without dementia. Methods: We conducted a population-based cross-sectional study using the 2016 National Ambulatory Medical Care Survey (NAMCS) in the US. Non-perioperative ambulatory care visits of patients ≥65 years old with sampling weights were used to provide national estimates of visits. Baseline characteristics were compared between visits for patients with and without dementia using Pearson's chi square or Student's t-tests. We used multivariable logistic regression to estimate the odds of receiving a new medication. Results: 218,182,131 non-perioperative ambulatory care visits of patients ≥65 years old were included, 2.1% of which were for patients with dementia; these patients were older on average and had more comorbidities and higher ambulatory care utilization than those without dementia. New medications were provided at 26.3% of visits for patients with dementia. After adjusting for confounders, there was no statistically significant difference in odds of a new medication being provided between visits for patients with and without dementia (odds ratio [OR], 0.555; 95% confidence interval [CI], 0.183-1.678). Differences were seen in the provision of cholinesterase inhibitors, antipsychotics, and central nervous system agents at visits for patients with dementia (p = 0.0011, <0.0001, and 0.0011 respectively). Conclusion: While fewer visits for patients with dementia provided new medications compared to patients without dementia, after adjusting for confounders no significant difference were identified. Significant differences were seen in the classes of new medications provided. Further investigation is needed to evaluate new medication usage and the utility of pharmacists in the care of patients with dementia at an outpatient setting.

Attitudes toward deprescribing in a middle-aged health disparities population.

BACKGROUND: Patients' attitudes toward deprescribing are crucial to understand before developing interventions, but no such data exists in the medically underserved, health disparities population of rural Appalachian United States. OBJECTIVE(S): Assess Appalachian women's openness to deprescribing medications and determine if polypharmacy influenced their attitudes toward deprescribing. METHODS: Before and after a cognitive behavioral therapy intervention, middle-aged Appalachian women self-reported medication use and completed the revised Patients' Attitudes Toward Deprescribing Questionnaire (rPATD). Responses were described, stratified by presence of polypharmacy. RESULTS: 30 women completed the rPATD pre- and post-intervention (mean [SD] age 55.8 [6.6] years; 96.7% white). Those with polypharmacy (n = 16) had higher burden and involvement scores (median 2.8 vs 2.0, p = 0.01; 4.9 vs 4.6, p = 0.06), and lower appropriateness scores (3.4 vs 3.9, p = 0.04). Burden, concerns about stopping, and involvement factor scores were similar before and after the intervention (p = 0.08, 0.86, and 0.41 respectively). ≥90% of participants were satisfied with their current medications yet would be willing to stop one or more. CONCLUSIONS: Middle-aged women in rural Appalachian United States are open to deprescribing; polypharmacy is associated with lower belief in the appropriateness of medications. Larger studies are needed to inform future deprescribing interventions for this and other similarly disadvantaged populations.

One-Year Evaluation of a Targeted Medication Therapy Management Intervention for Older Adults.

BACKGROUND: Older adults are especially susceptible to adverse effects of inappropriate medication therapy, and anticholinergic medications are common culprits for cognitive dysfunction due to their action on the central nervous system. Medication therapy management (MTM) interventions can aid in deprescribing and reducing inappropriate medication use in older adults. However, there is sparse literature on the long-term sustainability of these interventions. OBJECTIVES: To (a) investigate whether the deprescribing of anticholinergic medications during an 8-week randomized controlled trial (RCT) of a targeted MTM intervention is sustained at 1-year postintervention follow-up and (b) compare anticholinergic utilization trends in the study population with a large sample of similar individuals not exposed to the intervention. METHODS: Participants in the targeted MTM (tMTM) RCT had normal cognition or mild cognitive impairment and were recruited from enrollees in a longitudinal study at the University of Kentucky Alzheimer's Disease Center (ADC) and thus have pertinent medical information gathered approximately annually. In this posttrial observational follow-up, sustainability of the anticholinergic deprescribing intervention was assessed in participants in the RCT, and anticholinergic medication use trends were described from the RCT baseline (which occurred immediately following an ADC visit) to the next annual visit in all participants. Mean change in anticholinergic burden from RCT baseline to the next annual visit was estimated using analysis of covariance, and participants were compared with 2 external samples. Anticholinergic burden was measured using the Anticholinergic Drug Scale (ADS). The odds of decreasing baseline anticholinergic burden and number of total and strong anticholinergic medications at the follow-up study time point was assessed using logistic regression. RESULTS: Of the deprescribing changes made during the initial RCT, 50% were sustained after 1 year. Participants in the tMTM trial reported decreases in the use of anticholinergic antihistamines and bladder agents (-6.5 and -4.4%, respectively), but there was no change in the use of anticholinergic agents targeted at the central nervous system. While the anticholinergic burden of RCT participants decreased over 1 year (adjusted mean ADS change [95% CI] = -0.33 [-0.72, 0.07]), it was not different than the change observed in 2 external samples at the trial center (-0.20 [-0.42, 0.02]) and nationally (-0.33 [-0.39, -0.26]). There were no statistically significant differences between trial participants and external samples in the odds of decreasing anticholinergic burden nor in decreasing the number of total, or strongly anticholinergic, medications at the 1-year follow-up. CONCLUSIONS: This study demonstrates that the sustainability of deprescribing is limited to the period of intervention, rather than affording lasting effects even over periods as short as 1 year, which was demonstrated not only in the small group of RCT participants but also by comparison with external groups. Future work should extend the duration of intervention and follow-up periods for MTM interventions to allow further insights regarding the sustainability of deprescribing efforts in older adults. DISCLOSURES: The original trial was supported by a pilot study award from the University of Kentucky Center for Clinical and Translational Sciences (UL1TR000117). Additional support for this study was provided by the National Institutes of Health/National Institute on Aging (R01 AG054130). Jicha reports contract research for Esai, Biohaven, Alltech, Suven, Novartis, and Lilly. The other authors have nothing to disclose.

Statin Use and Gastrointestinal Hemorrhage: A Large Retrospective Cohort Study.

BACKGROUND: Nearly 70% of Americans with cardiovascular disease use statins, which have documented bleeding effects independent of their cholesterol-lowering activities. However, the literature is conflicting regarding the association between statin use and gastrointestinal hemorrhage. OBJECTIVES: The aim of this study was to investigate the risk of gastrointestinal hemorrhage in statin users. METHODS: In this retrospective cohort study, data from the Truven Health MarketScan® Research Database (2009-2015) were used to investigate the risk of gastrointestinal hemorrhage amongst statin users aged 30-65 years at the initial prescription claim. Statin users and a group of negative controls (i.e. other chronic medication users) were followed until first gastrointestinal hemorrhage event (both inpatient and outpatient, as well as restricted to inpatient), and were censored at treatment discontinuation, disenrollment from coverage, or the end of the study period. RESULTS: Statin users had an elevated risk of gastrointestinal hemorrhage, which was especially apparent in the first year of treatment (1-year adjusted hazard ratio 1.19; 95% confidence interval (CI) 1.15-1.23). The risk of gastrointestinal hemorrhage leading to hospitalization was even higher (1-year adjusted hazard ratio 1.38; 95% CI 1.30-1.69). High-intensity statin users had a greater rate of gastrointestinal hemorrhage than moderate-intensity users (incidence rates per 1000 subject-years 22.2 (95% CI 21.9-22.8) vs. 21.5 (95% CI 21.3-21.8), respectively). CONCLUSIONS: In a population of commercially insured subjects aged 30-65 years, statin users had a higher risk for gastrointestinal hemorrhage than other chronic medication users. These findings are important when treating patients at a high risk for bleeding events.

INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer's Symptomatic Expression (INCREASE), a randomized controlled trial: rationale, study design, and protocol.

BACKGROUND: The course of Alzheimer's disease (AD) includes a 10-20-year preclinical period with progressive accumulation of amyloid ß (Aß) plaques and neurofibrillary tangles in the absence of symptomatic cognitive or functional decline. The duration of this preclinical stage in part depends on the rate of pathologic progression, which is offset by compensatory mechanisms, referred to as cognitive reserve (CR). Comorbid medical conditions, psychosocial stressors, and inappropriate medication use may lower CR, hastening the onset of symptomatic AD. Here, we describe a randomized controlled trial (RCT) designed to test the efficacy of a medication therapy management (MTM) intervention to reduce inappropriate medication use, bolster cognitive reserve, and ultimately delay symptomatic AD. METHODS/DESIGN: Our study aims to enroll 90 non-demented community-dwelling adults ≥ 65 years of age. Participants will undergo positron emission tomography (PET) scans, measuring Aß levels using standardized uptake value ratios (SUVr). Participants will be randomly assigned to MTM intervention or control, stratified by Aß levels, and followed for 12 months via in-person and telephone visits. Outcomes of interest include: (1) medication appropriateness (measured with the Medication Appropriateness Index (MAI)); (2) scores from Trail Making Test B (TMTB), Montreal Cognitive Assessment (MoCA), and California Verbal Learning Test (CVLT); (3) perceived health status (measured with the SF-36). We will also evaluate pre- to post-intervention change in: (1) use of inappropriate medications as measured by MAI; 2) CR Change Score (CRCS), defined as the difference in scopolamine-challenged vs unchallenged cognitive scores at baseline and follow-up. Baseline Aß SUVr will be used to examine the relative impact of preclinical AD (pAD) pathology on CRCS, as well as the interplay of amyloid burden with inappropriate medication use. DISCUSSION: This manuscript describes the protocol of INCREASE ("INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer's Symptomatic Expression"): a randomized controlled trial that investigates the impact of deprescribing inappropriate medications and optimizing medication regimens on potentially delaying the onset of symptomatic AD and AD-related dementias. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02849639. Registered on 29 July 2016.