The impact of Alzheimer's disease risk factors on the pupillary light response.

Alzheimer's disease (AD) is the leading cause of dementia, and its prevalence is increasing and is expected to continue to increase over the next few decades. Because of this, there is an urgent requirement to determine a way to diagnose the disease, and to target interventions to delay and ideally stop the onset of symptoms, specifically those impacting cognition and daily livelihood. The pupillary light response (PLR) is controlled by the sympathetic and parasympathetic branches of the autonomic nervous system, and impairments to the pupillary light response (PLR) have been related to AD. However, most of these studies that assess the PLR occur in patients who have already been diagnosed with AD, rather than those who are at a higher risk for the disease but without a diagnosis. Determining whether the PLR is similarly impaired in subjects before an AD diagnosis is made and before cognitive symptoms of the disease begin, is an important step before using the PLR as a diagnostic tool. Specifically, identifying whether the PLR is impaired in specific at-risk groups, considering both genetic and non-genetic risk factors, is imperative. It is possible that the PLR may be impaired in association with some risk factors but not others, potentially indicating different pathways to neurodegeneration that could be distinguished using PLR. In this work, we review the most common genetic and lifestyle-based risk factors for AD and identify established relationships between these risk factors and the PLR. The evidence here shows that many AD risk factors, including traumatic brain injury, ocular and intracranial hypertension, alcohol consumption, depression, and diabetes, are directly related to changes in the PLR. Other risk factors currently lack sufficient literature to make any conclusions relating directly to the PLR but have shown links to impairments in the parasympathetic nervous system; further research should be conducted in these risk factors and their relation to the PLR.

A systematic review of the association between dementia risk factors and cerebrovascular reactivity.

Cumulative evidence suggests that impaired cerebrovascular reactivity (CVR), a regulatory response critical for maintaining neuronal health, is amongst the earliest pathological changes in dementia. However, we know little about how CVR is affected by dementia risk, prior to disease onset. Understanding this relationship would improve our knowledge of disease pathways and help inform preventative interventions. This systematic review investigates 59 studies examining how CVR (measured by magnetic resonance imaging) is affected by modifiable, non-modifiable, and clinical risk factors for dementia. We report that non-modifiable risk (older age and apolipoprotein ε4), some modifiable factors (diabetes, traumatic brain injury, hypertension) and some clinical factors (stroke, carotid artery occlusion, stenosis) were consistently associated with reduced CVR. We also note a lack of conclusive evidence on how other behavioural factors such as physical inactivity, obesity, or depression, affect CVR. This review explores the biological mechanisms underpinning these brain-behaviour associations, highlights evident gaps in the literature, and identifies the risk factors that could be managed to preserve CVR in an effort to prevent dementia.

Vascular smooth muscle cell dysfunction in neurodegeneration.

Vascular smooth muscle cells (VSMCs) are the key moderators of cerebrovascular dynamics in response to the brain's oxygen and nutrient demands. Crucially, VSMCs may provide a sensitive biomarker for neurodegenerative pathologies where vasculature is compromised. An increasing body of research suggests that VSMCs have remarkable plasticity and their pathophysiology may play a key role in the complex process of neurodegeneration. Furthermore, extrinsic risk factors, including environmental conditions and traumatic events can impact vascular function through changes in VSMC morphology. VSMC dysfunction can be characterised at the molecular level both preclinically, and clinically ex vivo. However the identification of VSMC dysfunction in living individuals is important to understand changes in vascular function at the onset and progression of neurological disorders such as dementia, Alzheimer's disease, and Parkinson's disease. A promising technique to identify changes in the state of cerebral smooth muscle is cerebrovascular reactivity (CVR) which reflects the intrinsic dynamic response of blood vessels in the brain to vasoactive stimuli in order to modulate regional cerebral blood flow (CBF). In this work, we review the role of VSMCs in the most common neurodegenerative disorders and identify physiological systems that may contribute to VSMC dysfunction. The evidence collected here identifies VSMC dysfunction as a strong candidate for novel therapeutics to combat the development and progression of neurodegeneration, and highlights the need for more research on the role of VSMCs and cerebrovascular dynamics in healthy and diseased states.

Perceptions of a virtual interview process for pharmacy residents during the COVID-19 pandemic: A multisite survey of residency candidates, preceptors, and residency program directors.

PURPOSE: To describe the perceptions of residency candidates, residency practitioners (current residents and preceptors), and residency program directors (RPDs) regarding a virtual interview process for pharmacy residency programs across multiple institutions. METHODS: In May 2021, an anonymous web-based questionnaire characterizing perceptions of the virtual interview process used during the coronavirus disease 2019 (COVID-19) pandemic was distributed to residency candidates, residency practitioners, and RPDs across 13 institutions. Quantitative responses measured on a 5-point Likert scale were summarized with descriptive statistics, and open-ended questions were analyzed using thematic qualitative methods. RESULTS: 236 residency candidates and 253 residency practitioners/RPDs completed the questionnaire, yielding response rates of 27.8% (236 of 848), and 38.1% (253 of 663), respectively. Overall, both groups perceived the virtual interview format positively. When asked whether virtual interviews should replace in-person interviews moving forward, 60.0% (18 of 30) of RPDs indicated they agreed or strongly agreed, whereas only 30.5% (61 of 200) of current preceptors/residents and 28.7% (66 of 230) of residency candidates agreed or strongly agreed. Thematic analysis of qualitative responses revealed that while virtual interviews were easier logistically, the lack of in-person interactions was a common concern for many stakeholders. Lastly, the majority (65.0%) of residency candidates reported greater than $1,000 in savings with virtual interviews. CONCLUSION: Virtual interviews offered logistical and financial benefits. The majority of RPDs were in favor of offering virtual interviews to replace in-person interviews, whereas the majority of residency candidates and practitioners preferred on-site interviews. As restrictions persist with the ongoing pandemic, our results provide insight into best practices for virtual pharmacy residency interviews.

Improved accuracy and precision with three-parameter simultaneous myocardial T1 and T2 mapping using multiparametric SASHA.

PURPOSE: To develop and validate a three-parameter model for improved precision multiparametric SAturation-recovery single-SHot Acquisition (mSASHA) cardiac T1 and T2 mapping with high accuracy in a single breath-hold. METHODS: The mSASHA acquisition consists of nine images of variable saturation recovery and T2 preparation in 11 heartbeats with T1 and T2 values calculated using a three-parameter model. It was validated in simulations and phantoms at 3 T with comparison to a four-parameter joint T1 -T2 technique. The mSASHA acquisition was compared with MOLLI, SASHA, and T2 -prepared balanced SSFP in 10 volunteers. RESULTS: The mSASHA technique had high accuracy in phantoms compared to spin echo, with -0.2 ± 0.3% T1 error and -2.4 ± 1.3% T2 error. The mSASHA coefficient of variation in phantoms for T1 was similar to MOLLI (0.7 ± 0.2% for both) and T2 -prepared balanced SSFP for T2 (1.3 ± 0.7% vs 1.4 ± 0.3%, adjusted p > .05 for both). In simulations, three-parameter mSASHA had higher precision than four-parameter joint T1 -T2 for both T1 and T2 (46% and 11% reductions in T1 and T2 interquartile range for native myocardium). In vivo myocardial mSASHA T1 was similar to SASHA (1523 ± 18 ms vs 1520 ± 18 ms) with similar coefficient of variation to both MOLLI and SASHA (3.3 ± 0.6% vs 3.1 ± 0.6% and 3.3 ± 0.5% respectively, adjusted p > .05 for all). Myocardial mSASHA T2 was 37.1 ± 1.1 ms with similar precision to T2 -prepared balanced SSFP (6.7 ± 1.7% vs 6.0 ± 1.6%, adjusted p > .05). CONCLUSION: Three-parameter mSASHA provides high-accuracy cardiac T1 and T2 quantification in a single breath-hold with similar precision to MOLLI and T2 -prepared balanced SSFP. Further study is required to both establish normative values and demonstrate clinical utility in patient populations.

Economic Evaluation of Changes in Reimbursement for Medications Purchased Through the 340B Drug Pricing Program.

Background: The Centers for Medicare and Medicaid Services (CMS) implemented changes to the reimbursement scheme for 340B-acquired medications on January 1, 2018, reducing payments by approximately 25%. It was recognized that these changes would have a significant fiscal impact to Medical University of South Carolina (MUSC) Health. The purpose of this assessment was to review the financial impact of changes in Medicare reimbursement for clinic-administered medications. Methods: This study was a single-center, retrospective, financial evaluation of closed outpatient encounters for Medicare beneficiaries in calendar year 2018. Actual reimbursement was calculated for 2018. To better characterize the margin obtained, exploratory analyses were completed to identify best- and worst-case reimbursement outcomes. This exploratory analysis was conducted for both the new (ASP-22.5%) and old (ASP+6%) reimbursement schemes. Results: Overall, 10 973 encounters were reviewed for inclusion. Ultimately, 8028 encounters were included in the final analysis. Of all encounters, 88 unique medications were administered. Most of the drugs (55%) were associated with oncologic indications. An unfavorable variance was found in 3761 encounters (47%). The actual reimbursement margin for 2018 was $3 193 525. Conclusion: Changes to reimbursement outlined by the CMS at the start of 2018 resulted in decreased reimbursement for 340B-eligible, clinic-administered medications. Most of the unfavorable variances were associated with 340B acquisition prices that exceeded reimbursement. Although the original intent of the 340B Drug Pricing Program was to stretch federal resources, decreased payments could reduce institutional ability to fund programs that support medically vulnerable populations.

Use of economic predictions to make formulary decisions.

PURPOSE: The accuracy of cost savings and reimbursement predictions for medications added to an academic medical center formulary was assessed. METHODS: Formulary changes over a 5-year period were reviewed by the investigators. Medications were included if the medication was added to formulary and the monograph included cost savings or reimbursement data that indicated a positive net margin. The primary endpoints were percent predicted cost savings and net margin per medication based on medication cost only. Secondary endpoints included the percent of medications with at least 100% predicted cost savings or net margin and evaluation of median percent predicted savings or net margin individually. RESULTS: The pharmacy and therapeutics committee reviewed 558 formulary agenda items, 184 of which were selected for further analysis. In total, 19 medications were identified as having a predicted monetary advantage. The endpoints of percent predicted cost savings and net margin yielded a median of 76.5% (range 72.9-188.71%) (n = 3) and 148.2% (IQR 108.9-543.3%) (n = 16), respectively. For 13 (68%) of 19 medications, the percent predicted cost savings or net margin was at least 100%. CONCLUSION: Economic predictions utilized for formulary management at an academic medical center generated net positive monetary value for medications where predicted cost savings or reimbursement factored into the decision to add a medication to the formulary.

Thiamine Prescribing and Wernicke's Encephalopathy Risk Factors in Patients With Alcohol Use Disorders at a Psychiatric Hospital.

BACKGROUND: Alcohol use disorder (AUD) is the leading cause of thiamine deficiency and can lead to Wernicke's encephalopathy (WE). WE has a higher prevalence of development in patients with AUD, and current recommendations emphasize parenteral administration of thiamine. Our objective was to characterize thiamine utilization in patients with AUD who were prescribed thiamine and evaluate if those who received oral thiamine had risk factors for the development of WE. METHODS: This retrospective chart review enrolled adults admitted to a psychiatric hospital from October 2014 through September 2015 diagnosed with AUD as per the International Classification of Diseases, Ninth Edition (ICD-9). The cohort was divided on the basis of route of thiamine administration (nonparenteral vs. parenteral) and was then screened retrospectively for risk factors for WE. Descriptive data and measures of central tendency were utilized to assess the objectives. RESULTS: The majority of patients were white male individuals, with a mean age of 48 years. Of the 226 patients, 201 (89%) were prescribed oral thiamine. Of the first 100 patients who received oral thiamine, 36% had risk factors for WE, with the most common risk factor being malnutrition. A χ analysis revealed that WE risk factors did not influence route of thiamine administration (χ=2.148, df=1, P=0.143). No patients were diagnosed with WE during their admission; however, 8 patients received parenteral thiamine at a treatment dose indicated for WE. CONCLUSIONS: Parenteral thiamine is underutilized in patients with AUD and risk factors for WE. Education is needed to enhance thiamine prescribing and evaluation of risk factors for WE in this population. A thiamine prescribing protocol has been developed for further thiamine optimization.

Assessment of venous thromboembolism risk and initiation of appropriate prophylaxis in psychiatric patients.

INTRODUCTION: Venous thromboembolism (VTE) prophylaxis is not included among the measures for the Inpatient Psychiatric Facilities Quality Reporting Program. Evidence suggests that antipsychotic agents may be an independent risk factor for the development of VTE; therefore, development of a VTE risk stratification tool would improve the quality and safety of care for the psychiatric inpatient population. This study aims to develop clinically relevant criteria to assess VTE risk upon admission to an inpatient psychiatric hospital. METHODS: This retrospective, single-center cohort study enrolled patients in 2 cohorts from an inpatient psychiatric hospital. Patients in cohort I with new-onset VTE diagnosis during admission were identified through international classification of diseases 9 and 10 coding. Cohort II consisted of a random sample of 100 patients in a 3-month period. The percentage meeting criteria for prophylaxis in each cohort was assessed utilizing both the Padua Prediction Score and a modified score. RESULTS: In cohorts I and II, 66.7% and 14% of patients, respectively, met criteria for VTE prophylaxis utilizing the modified Padua Prediction Score. One patient received VTE prophylaxis in each cohort, and the median time to VTE diagnosis in cohort I was 42 days. In cohort I, the rate of VTE was 0.08% based on estimated discharges in the 26-month period. This is less than the annual rate of 1% to 2.4% for nursing homes or postacute rehabilitation facilities. DISCUSSION: We recommend the implementation of clinical decision support to prompt individualized reassessment of VTE risk when length of stay exceeds 30 days.

Evaluation of a medication intensity screening tool used in malignant hematology and bone marrow transplant services to identify patients at risk for medication-related problems.

Background In 2014, a screening tool was implemented at Medical University of South Carolina (MUSC) Health to identify patients who are at risk for medication-related events. Patients are classified as high-risk if they meet one of the following criteria: receiving anticoagulation therapy, taking more than 10 scheduled medications upon admission, or readmission within the past 30 days. The goal of this study was to determine risk criteria specific to the malignant hematology (MH) and bone marrow transplant (BMT) patients. Methods A retrospective chart review of 114 patients admitted and discharged from the MH/BMT services between 1 September 2015 and 31 October 2015 was performed. A pharmacist-conducted medication history was completed and documented, and all interventions at admission and throughout hospitalization were categorized by severity and by value of service. The primary objective was to evaluate if patients in the MH/BMT services have more medication-related interventions documented upon admission compared with patients who are not screened as high risk. The secondary objectives were to evaluate the different types and severities of interventions made by pharmacists during the entire hospital stay, and to determine if there are certain characteristics that can help identify hematology/oncology high-risk patients. Results More interventions documented upon admission in the high-risk group as a whole when compared with the not high-risk group (73 vs. 31), but when normalized per patients in each group, there was an equal number of interventions (1.0). The most common interventions were to modify regimen (36%) and discontinue therapy (16%). The patient characteristics associated with high-risk included neutropenia, lower average platelet counts on admission, and longer length of stay. Conclusion The screening tool does not further differentiate an already complex MH/BMT patient population. Pharmacists may be more useful at capturing errors or changes during a patient's hospital stay instead of upon admission. Thrombocytopenia, neutropenia, and active infections may correlate with higher-risk status.

Effect of Subcutaneous Unfractionated Heparin Prophylaxis on Activated Partial Thromboplastin Time: A Retrospective Evaluation.

STUDY OBJECTIVE: Characterize the incidence of elevated aPTT results in patients treated with prophylactic, subcutaneous unfractionated heparin (UFH). DESIGN: Retrospective, cohort analysis. SETTING: Single-center, university hospital. MEASUREMENTS: Evaluation of 257 patients with activated partial thromboplastin time (aPTT) testing both prior to and following subcutaneous (SC) unfractionated heparin (UFH) therapy. MAIN RESULTS: Evaluated patients received UFH 5000 units every 8 hours. Baseline aPTT values were within the normal range (mean±SD, 32.0±8.5 seconds). After initiation of UFH, aPTT values increased (mean±SD, 37.6±15.2 seconds). After 24 hours of SC UFH, mean aPTT values (mean±SD, 38.6±15.5) exceeded the normal laboratory range (23.3-35.7 seconds). An elevated aPTT result after UFH was associated with baseline aPTT, length of therapy, and weight-based UFH dose. A significant association was not identified between aPTT elevation and age, race, sex, history of liver disease, type of admission, or transfusion of blood products. CONCLUSIONS: Treatment with UFH resulted in a small, but significant, increase in aPTT.

Clinical and Financial Impact of Pharmacist Involvement in Discharge Medication Reconciliation at an Academic Medical Center: A Prospective Pilot Study.

BACKGROUND: Medication reconciliation is one of the more challenging aspects of inpatient care, and its accuracy is paramount to safe transitions of care. Studies have shown that pharmacists have a role in medication reconciliation through improving patient safety and avoiding costs associated with medication errors. The wide-scale use of pharmacists in this process has been limited by time constraints, cost, and lack of resources. OBJECTIVE: This study evaluates the impact of pharmacists in resolving medication errors, decreasing readmission rates, and reducing institutional costs during the discharge medication reconciliation process. METHODS: Pharmacists evaluated discharge medication reconciliation documentation for patients to determine its accuracy, the accuracy of the admission reconciliation documentation, and any potential issues unrelated to accuracy. Analysis of these data determined the time required for pharmacist involvement, the number of errors identified by pharmacists, the quality of pharmacist interventions, the cost avoidance for each error, and the overall impact on hospital readmission. RESULTS: During the 7-week study period, pharmacists performed 67 discharge medication reviews and identified 84 errors. Seventy-five percent were considered to be significant and 6% were considered to be serious. The 30-day readmission rate in the study cohort was 18% compared with 20% in the control group. Based on the clinical severity scale and pharmacist salaries, pharmacist interventions resulted in $42,300 in cost avoidance. CONCLUSION: Pharmacists involved in this pilot discharge process identified and resolved significant errors on medication reconciliation orders that resulted in a financial benefit to the institution.

Evaluation of discharge medication orders following automatic therapeutic substitution of commonly exchanged drug classes.

OBJECTIVE: Automatic therapeutic substitution (ATS) is a mechanism that, upon patient hospitalization, prompts the pharmacist to exchange an equivalent formulary drug for a nonformulary medication, typically without prescriber contact. In facilities utilizing ATS, there is the possibility that physicians and patients may be unaware of the substitution, potentially leading to drug-drug interactions, therapeutic duplication, and/or increased patient expense following discharge should the original regimen not be resumed. The purpose of this study was to determine the frequency with which hospitalized patients subjected to an ATS protocol were not returned to outpatient drug therapy. METHODS: A retrospective chart review of adult patients admitted to an academic medical center between January 1 and June 30, 2011, was conducted. Patients were included if they were admitted on angiotensin-converting enzyme (ACE) inhibitors, antidepressants, nonsedating antihistamines, histamine (H2) receptor antagonists, or proton pump inhibitors (PPIs), and were then prescribed a different agent via ATS. Admission and discharge medication reconciliation documents, dictated discharge summaries, and patient education documentation reports were reviewed for drug therapies and doses, as well as medication counseling evidence. The primary endpoint was the percentage of patients not returned to original outpatient therapy following ATS. Secondary endpoints included prescribing events in patients not returned to original therapy, the rate and source of drug therapy counseling at discharge, and the number of patients discharged on a potentially cost-prohibitive drug, defined as any drug available only as a branded product during the study period. RESULTS: A total of 317 interventions were identified through review of pharmacy records. Of these, 47 patients (15%) were not returned to original outpatient therapy. Within this subsection, 15 patients (32%) were discharged on the substituted drug, eight patients (17%) resumed initial therapy but received a dosage adjustment from previous outpatient therapy, and three patients (6%) were discharged on a drug that was neither the substituted product nor the previous outpatient therapy. The remaining 21 patients had therapy discontinued (n = 12/47, 26%) or lacked documentation of discharge therapy (9/47, 19%). Nursing staff provided medication counseling to 288 of the 317 patients (91%). Overall, 51 patients (16%) were identified as receiving a cost-prohibitive drug. CONCLUSION: Patients subject to ATS of commonly substituted drug classes were returned to their original outpatient drug therapy more than 85% of the time following inpatient hospitalizations, with similar rates of medication counseling at discharge. The prescribing of cost-prohibitive drugs has been identified as a potential area for pharmacist intervention at discharge.

Nutritional supplements in critical illness.

Poor nutritional intake during critical illness can contribute to increased morbidity and mortality. Although nutrition strategies for critically ill patients attempt to provide essential macronutrients, recent evidence suggests that certain micronutrients and supplements may improve wound healing and decrease infectious and inflammatory complications. This review will focus on mechanism of action, adverse effects and drug interactions reported in the literature, and appropriate dosing and outcomes data for specific nutritional supplements in various critically ill adult populations.