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Background: During the COVID-19 pandemic, people have been required to follow preventive measures such as government policy including the closure of exercise facilities and movement restriction, can lead to an unhealthy lifestyle. We investigated the effect of these preventive measures on metabolic parameters in individuals with cardiometabolic disorders.Methods: In the current retrospective observational study of patients who visited the hospital at least twice a year for the past 4 years, changes in cardiometabolic factors from the COVID-19 pandemic (2019–2020) were compared with changes in the same cohort at the same annual time points during the previous seasons of 2016–2019.Results: A total of 1,485 individuals with a mean age of 61.8 ± 11.7 years were included in the analysis. During the COVID-19 pandemic, the number of patients whose metabolic syndrome worsened increased significantly by 21% compared with the 2018–2019 season. The body mass index increased by 0.09 ± 1.16 kg/m2 in the 2019–2020 pandemic period, whereas it decreased by –0.39 ± 3.03 kg/m2 in 2018–2019 and by –0.34 ± 2.18 kg/m2 in 2017–2018 (both p < 0.05). Systolic blood pressure increased by 2.6 ± 18.2 mmHg in the COVID-19 pandemic period, while it decreased in the three antecedent seasons (all p < 0.05). The lipid profiles worsened in the pandemic period compared with the previous years. The Framingham coronary heart disease risk score also increased significantly.Conclusions: With preventive procedures during the contagious disease pandemic, nationwide strategies to maintain cardiometabolic health are necessary.

Background The clinical implementation of pharmacogenomics (PGx) has often involved teams that include pharmacists. PGx laboratories often provide baseline information within the laboratory report that is based on Food and Drug Administration and Clinical Pharmacogenomics Implementation Consortium guidance, but information is often provided independent of concurrent disease states or medication use, among other clinical factors. Major challenges to widescale implementation of PGx include lack of physician experience or confidence in interpreting the data. The purpose of this paper is to describe how pharmacists can help further personalize PGx information and identify clinical recommendations for a given patient. Methods This work was performed as a secondary objective of a study evaluating genetic biomarkers of opioid addiction risk. This portion of the study utilized a descriptive analysis of pharmacist consult reports that consist of individualized, patient-level clinical recommendations that take into account current medications, current health conditions, and PGx data. A panel of 60 common PGx targets were tested among patients being treated for chronic pain or opioid use disorder (OUD). A pharmacist consult report was generated and compared with standard laboratory reporting of general PGx information. Results Of the 252 patients, PGx reports for 198 (78.6%) contained red and/or yellow clinical decision support flags for medications with actionable or informative PGx guidance for currently prescribed medications. Pharmacists recommended modifications to current prescriptions for 31 (53%) of the patients with actionable flags and 17 (12%) of the patients with informative flags. Drug classes most commonly included medications for cardiology, depression and anxiety, pain (opioids) and gastrointestinal management. Taken together, 24.2% of the actionable and informative flags had immediate clinical value based on the pharmacist's review. An additional 217 (86%) received one or more clinical recommendations not related to PGx. Conclusion While PGx provides another opportunity for pharmacotherapy personalization, PGx data must be considered within the context of other patient-specific factors. Pharmacists were able to streamline the PGx report flags and identify other pharmacotherapy interventions following application of patient-specific data, thereby developing a brief report of recommendations for the patient's prescriber(s). Engaging clinical pharmacists in the PGx clinical decision process may help to facilitate more widespread PGx implementation.

The rheological and physiological properties of red blood cells (RBCs) are affected by many factors in the vascular environment. Among them, membrane fluctuations (MFs), particularly dynamic fluctuations in RBC cell membrane thickness (RBC-MFs), are likely to be altered by the level of glycation of haemoglobin in patients with diabetes mellitus (DM). We investigated the associations of RBC-MFs with physiological variables associated with DM and cardiovascular diseases (CVDs). Forty-one healthy control subjects and 59 patients with DM were enrolled. Five-microliter samples of blood were collected and diluted 400 times. To measure the RBC-MFs, holotomography was used, which non-invasively and precisely analyses the optical characteristics of RBCs. Associations between the RBC-MFs and biochemical parameters related to glucose homeostasis and lipid profiles were investigated. Independent associations of the RBC-MFs with the presence of CVDs were also analysed. RBC-MFs were lower in patients with DM than in healthy participants (61.64 ± 7.49 nm vs 70.65 ± 6.65 nm, P = 1.4 × 10

(1) Background: The study aimed to analyze the effectiveness of clinical pharmacist services on drug-related problems (DRPs) and patient outcomes in inpatients with chronic kidney disease (CKD). (2) Methods: In a randomized controlled trial, the participants in the intervention group received pharmacist services, including medication reconciliation, medication evaluation and management, and discharge pharmaceutical care transition services. Participants in the control group received usual care. The primary outcome was the number of DRPs per patient at discharge. (3) Results: The baseline characteristics of 100 participants included the following: mean age, 52.5 years, median eGFR, 9.2 mL/min/1.73 m2. The number of DRPs in the intervention group during hospitalization increased significantly with decreasing eGFR (PR, 0.970, 95% CI, 0.951–0.989) and an increasing number of unintentional medication discrepancies at admission (PR, 1.294, 95% CI, 1.034–1.620). At discharge, the number of DRPs per patient was 0.94 ± 1.03 and 1.96 ± 1.25 in the intervention and control groups, respectively (p &lt, 0.001). The service had a significant effect on the reduction of the unintentional discrepancies at discharge (p &lt, 0.001). (4) Conclusion: Hospital pharmacists play an important role in the prevention of DRPs at discharge and unintentional medication discrepancies in inpatients with CKD.

The rheological and physiological properties of red blood cells (RBCs) are affected by many factors in the vascular environment. Among them, membrane fluctuations (MFs), particularly dynamic fluctuations in RBC cell membrane thickness (RBC-MFs), are likely to be altered by the level of glycation of haemoglobin in patients with diabetes mellitus (DM). We investigated the associations of RBC-MFs with physiological variables associated with DM and cardiovascular diseases (CVDs). Forty-one healthy control subjects and 59 patients with DM were enrolled. Five-microliter samples of blood were collected and diluted 400 times. To measure the RBC-MFs, holotomography was used, which non-invasively and precisely analyses the optical characteristics of RBCs. Associations between the RBC-MFs and biochemical parameters related to glucose homeostasis and lipid profiles were investigated. Independent associations of the RBC-MFs with the presence of CVDs were also analysed. RBC-MFs were lower in patients with DM than in healthy participants (61.64 ± 7.49 nm vs 70.65 ± 6.65 nm, P = 1.4 × 10−8). RBC-MFs correlated modestly with glycated haemoglobin level (ρ = − 0.47) and weakly with age (ρ = − 0.36), duration of diabetes (ρ = − 0.36), fasting plasma glucose level (ρ = − 0.37), and the 10-year Framingham risk score (ρ = − 0.38) (all P

The opioid epidemic has had a devastating impact on our country, with wide-ranging effects on healthcare, corrections, employment, and social systems. Programs have been put in place for monitoring prescriptions, initiating and expanding medications for opioid use disorder, and harm reduction (i.e., naloxone distribution, needle exchanges). However, opportunities for personalization of opioid therapy based on addiction risk have been limited. The goal of the present study was to develop an objective risk assessment algorithm based on genetic markers that are correlated with opioid use disorder (OUD). A total of 180 single-nucleotide polymorphisms (SNPs) were tested in patients with and without OUD. SNPs selected for testing were associated with opioid metabolism and drug reward pathways based on previous studies. Of the 394 patients recruited, 200 had OUD and 194 served as controls without OUD but with prior opioid exposure. Logistic regression analyses stratified by sex identified ten unique SNPs in females and nine unique SNPs in males that were significantly associated with OUD. A Genetics Opioid Risk Score (GenORs) was calculated by counting the number of OUD risk-associated SNPs/genotypes for each patient. To evaluate the discrimination of the GenORs, a receiver operating characteristic (ROC) curve for each sex was generated and determined to be sensitive and specific. This represents the first published example of a sex-based genetic risk score with potential to predict OUD, and the first OUD algorithm to include opioid-associated pharmacokinetic genes.

Objectives The objective of the study was to estimate the national rates of naloxone coprescribing with opioids in office-based practice and emergency department (ED) settings in the United States (US). Study design This study is a cross-sectional study. Methods We used the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS) datasets to estimate the national rates of naloxone coprescribing with opioids for the period 2014–2016. The analysis was stratified into office-based practice and ED settings. In ED settings, opioid and naloxone could be given to patients while they were in ED or as a prescription at discharge. Patients of all ages were considered for the analysis and sampling weights were applied to estimate national rates. Results In office-based settings, 7918 sample visits included one or more opioid prescriptions (10.67 per 100 office visits). Of those, one included naloxone as a coprescription. In ED settings, the opioid prescription was given at discharge in 6124 sample visits (9.68 per 100 ED visits). Of those, two included naloxone as a coprescription. On the other hand, opioid was given to patients in the ED in 8811 sample visits (13.57 per 100 ED visits). Of those, 30 included naloxone as a coprescription. Conclusions The rates of naloxone coprescribing with opioids were extremely low in office-based and ED settings in the US. Expanding access to naloxone is a key component of the public health response to the opioid crisis. Based on our study findings, promoting the coprescription of naloxone with opioids may provide greater access to naloxone for those who are at risk of opioid overdose.

Objective As uncontrolled hyperuricemia has been associated with an increased risk of cardiovascular disease and the progression of chronic kidney disease (CKD), management of serum uric acid levels is important. The aim of this study was to evaluate the effectiveness of febuxostat in regulating uncontrolled hyperuricemia in patients with renal dysfunction. Materials and methods We included patients with CKD and persistent uncontrolled hyperuricemia despite treatment with allopurinol. The primary outcome of the study, which was the overall response rate of febuxostat, was defined as the proportion of patients that achieved a serum uric acid level l 7.0 mg/dL. The secondary outcomes included the change in renal function and factors that might influence treatment outcomes. The safety outcome was evaluated based on the incidence of adverse reactions. Results A total of 111 patients who switched medication to febuxostat were included. Febuxostat treatment significantly lowered serum uric acid level and the response rates were above 70% at all the time points for 1 year. Febuxostat-treated patients demonstrated no significant change in renal function during the study period. A history of gout attack decreased the response rate of febuxostat (odds ratio (OR): 3.13, 95% confidence interval (CI): 1.08 - 9.06), whereas low-dose aspirin use significantly increased response rate (OR: 0.29, 95% CI: 0.09 - 0.92) in the first month. No patients experienced any severe adverse events. Conclusions Febuxostat effectively lowered serum uric acid levels and was well tolerated in patients with CKD and allopurinol-refractory hyperuricemia. .

BACKGROUND AND OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) medication use and psychotherapeutic polypharmacy is increasing. This study was designed to assess annual rates of ADHD medication prescribing and psychotherapeutic polypharmacy among patients 2 to 24 years old in the United States, identify commonly prescribed ADHD medications and concomitant psychotropic agents, and assess if specific characteristics are associated with polypharmacy. METHODS: In this cross-sectional study, we used publicly available ambulatory health care data sets to evaluate ADHD and psychotropic polypharmacy use in patients 2 to 24 years old from 2006 to 2015. National rates were estimated by using sampling weights, and common ADHD and psychotropic drugs prescribed were identified. Multivariate logistic regression models were developed to assess the strength of association between polypharmacy and patient or provider characteristics. RESULTS: Between 2006 and 2015, ADHD medication prescribing increased from 4.8% to 8.4%. ADHD polypharmacy increased from 16.8% to 20.5%, whereas psychotropic polypharmacy increased from 26.0% to 40.7%. The most common ADHD combinations were stimulants and α-2 agonists (67.1%), whereas the most common concomitant psychotropic agents were selective serotonin reuptake inhibitors (14.4%) and second-generation antipsychotics (11.8%). Factors associated with polypharmacy were age, female sex (psychotropic), nonprivate insurance, northeast and south regions (ADHD), receipt of mental health counseling or psychotherapy, and calendar year. CONCLUSIONS: ADHD and psychotropic polypharmacy use is increasing and associated with specific patient characteristics. These patterns should spark further inquiry about the appropriateness, efficacy, and safety of psychotherapeutic polypharmacy in children and young adults, particularly within subgroups in which the use is high.

OBJECTIVE: To test whether Medicaid expansion is associated with (a) a greater number of naloxone prescriptions dispensed and (b) a higher proportion of naloxone prescriptions paid by Medicaid. DATA SOURCES/STUDY SETTING: We used the IQVIA National Prescription Audit to obtain data on per state per quarter naloxone prescription dispensing for the period 2011‐16. STUDY DESIGN: In this quasi‐experimental design study, the impact of Medicaid expansion on naloxone prescription dispensing was examined using difference‐in‐difference estimation models. State‐level covariates including pharmacy‐based naloxone laws (standing/protocol orders and direct authority to dispense naloxone), third‐party prescribing laws, opioid analgesic prescribing rates, opioid‐involved overdose death rates, and population size were controlled for in the analysis. PRINCIPAL FINDINGS: Medicaid expansion was associated with 38 additional naloxone prescriptions dispensed per state per quarter compared to nonexpansion controls, on average (P = .030). Also, Medicaid expansion resulted in an average increase of 9.86 percent in the share of naloxone prescriptions paid by Medicaid per state per quarter (P

Key Points Question Are legal mandates for naloxone coprescription associated with increases in naloxone prescription dispensing? Findings In this population-based, state-level cohort study using data from retail pharmacies in all 50 states and the District of Columbia, having a legal mandate for naloxone coprescription was associated with approximately 7.75 times more dispensed naloxone prescriptions compared with not having the requirements. This equates to an estimated 214 additional naloxone prescriptions dispensed per month in the period following the mandates, holding all other variables constant. Meaning State legal interventions that mandate naloxone coprescription for potentially at-risk patients may be associated with increases in naloxone prescription dispensing in retail pharmacies, and this strategy may be useful to improve naloxone availability and reduce opioid-related harm., Importance To mitigate the opioid overdose crisis, states have implemented a variety of legal interventions aimed at increasing access to the opioid antagonist naloxone. Recently, Virginia and Vermont mandated the coprescription of naloxone for potentially at-risk patients. Objective To assess the association between naloxone coprescription legal mandates and naloxone dispensing in retail pharmacies. Design, Setting, and Participants This was a population-based, state-level cohort study. The sample included all prescriptions dispensed for naloxone in the retail pharmacy setting contained in IQVIA’s national prescription audit, which represents 90% of all retail pharmacies in the United States. The unit of observation was state-month and the study period was January 1, 2011, to December 31, 2017. Exposures State legal intervention mandating naloxone coprescription. Main Outcomes and Measures Number of naloxone prescriptions dispensed. State rates of naloxone prescriptions dispensed per month per 100 000 standard population were calculated. Results The rate of naloxone dispensing increased after implementation of legal mandates for naloxone coprescription. An estimated 88 naloxone prescriptions per 100 000 were dispensed in Virginia and 111 prescriptions per 100 000 were dispensed in Vermont during the first full month the legal requirement was effective. In comparison, 16 naloxone prescriptions per 100 000 were dispensed in the 10 states (including the District of Columbia) with the highest opioid overdose death rates and 6 prescriptions per 100 000 were dispensed in the 39 remaining states. The number of naloxone prescriptions dispensed was associated with the legal mandate for naloxone coprescription (incidence rate ratio [IRR], 7.75; 95% CI, 1.22-49.35). Implementation of the naloxone coprescription mandate was associated with an estimated 214 additional naloxone prescriptions dispensed per month in the period following the mandates, holding all other variables constant. Among covariates, naloxone access laws (IRR, 1.37; 1.05-1.78), opioid overdose death rates (IRR, 1.06; 95% CI, 1.04-1.08), the percentage of naloxone prescriptions paid by third-party payers (IRR 1.009; 1.008-1.010), and time (IRR, 1.06; 95% CI, 1.05-1.07) were significantly associated with naloxone prescription dispensing. Conclusions and Relevance These study findings suggest that legally mandated naloxone prescription for those at risk for opioid overdose may be associated with substantial increases in naloxone dispensing and further reduction in opioid-related harm., This population-based cohort study examines the rates of naloxone coprescription since implementation of state laws mandating coprescription for persons at risk for opioid overdose.

The purpose of this study was to identify genotypes associated with dose-adjusted tacrolimus trough concentrations (C0/D) in kidney transplant recipients using whole-exome sequencing (WES). This study included 147 patients administered tacrolimus, including seventy-five patients in the discovery set and seventy-two patients in the replication set. The patient genomes in the discovery set were sequenced using WES. Also, known tacrolimus pharmacokinetics-related intron variants were genotyped. Tacrolimus C0/D was log-transformed. Sixteen variants were identified including novel CYP3A7 rs12360 and rs10211 by ANOVA. CYP3A7 rs2257401 was found to be the most significant variant among the periods by ANOVA. Seven variants including CYP3A7 rs2257401, rs12360, and rs10211 were analyzed by SNaPshot in the replication set and the effects on tacrolimus C0/D were verified. A linear mixed model (LMM) was further performed to account for the effects of the variants and clinical factors. The combined set LMM showed that only CYP3A7 rs2257401 was associated with tacrolimus C0/D after adjusting for patient age, albumin, and creatinine. The CYP3A7 rs2257401 genotype variant showed a significant difference on the tacrolimus C0/D in those expressing CYP3A5, showing its own effect. The results suggest that CYP3A7 rs2257401 may serve as a significant genetic marker for tacrolimus pharmacokinetics in kidney transplantation.

Objective The purpose of this study was to examine the association between mental disorder comorbidity and in-hospital mortality, and whether subgroups of mental disorder comorbidity have differential impacts on in-hospital mortality in acute myocardial infarction (AMI) patients. Methods A cross-sectional study was conducted using the 2010 Nationwide Inpatient Sample (NIS) database of the Healthcare Cost and Utilization Project (HCUP). The study sample included discharges for which the primary diagnosis was AMI. As the primary exposure, the presence of any mental disorder comorbidity was identified as discharges for which one or more mental disorders listed as the non-primary diagnosis. The secondary exposure was subgroups of the mental disorder comorbidity (schizophrenia, major affective disorder, substance abuse, and other). The outcome of interest was in-hospital mortality. Logistic regression and resulting odds ratios (ORs) with associated 95% confidence intervals (CIs) were used to estimate the impact of mental disorder comorbidity on in-hospital death. Results A total of 42,416 discharges were included in the analysis. Of these, 16,140 (38%) had at least one diagnosis of a mental disorder. No significant differences were observed in in-hospital mortality between patients with and without mental disorder comorbidity. However, when the mental disorder comorbidity is specified into subgroups, the impact differentiated depending on the subgroup. More specifically, patients with schizophrenia were associated with increased in-hospital mortality (OR 1.72, 95% CI 1.02–2.90) and patients with substance abuse disorder were associated with decreased in-hospital mortality (OR 0.80, 95% CI 0.70–0.91). Major affective disorder and other mental disorders were not statistically significant. Conclusions Mental disorder comorbidity has a differential impact on post-AMI in-hospital mortality depending on the subgroup of mental disorders. We argue that mental disorder comorbidity should not be treated as a single category when assessing its impact on a health outcome.

The purpose of the study was three-fold: (1) to estimate the national trends in antipsychotic (AP) polypharmacy among 6- to 24-year-old patients in the U.S.; (2) to identify frequently used AP agents and mental disorder diagnoses related to AP polypharmacy; and (3) to assess the strength of association between AP polypharmacy and patient/provider characteristics. We used publicly available ambulatory health care datasets to evaluate AP polypharmacy in office-based or hospital outpatient department settings to conduct a cross-sectional study. First, national visit rates between 2007 and 2011 were estimated using sampling weights. Second, common diagnoses and drugs used in AP polypharmacy were identified. Third, a multivariate logistic regression model was developed to assess the strength of association between AP polypharmacy and patient and provider characteristics. Between 2007 and 2011, approximately 2% of office-based or hospital outpatient department visits made by 6- to 24-year-old patients included one or more AP prescriptions. Of these visits, 5% were classified as AP polypharmacy. The most common combination of AP polypharmacy was to use two or more second-generation APs. Also, bipolar disorder and schizophrenia were the two most frequent primary mental disorder diagnoses among AP polypharmacy visits. The factors associated with AP polypharmacy were: older age (young adults), black, having one or more non-AP prescriptions, and having schizophrenia or ADHD.

Fenofibrate activates not only peroxisome proliferator-activated receptor-α (PPARα) but also adenosine monophosphate-activated protein kinase (AMPK). AMPK-mediated cellular responses protect kidney from high-fat diet (HFD)-induced injury, and autophagy resulting from AMPK activation has been regarded as a stress-response mechanism. Thus the present study examined the role of AMPK and autophagy in the renotherapeutic effects of fenofibrate. C57BL/6J mice were divided into three groups: normal diet (ND), HFD, and HFD + fenofibrate (HFD + FF). Fenofibrate was administered 4 wk after the initiation of the HFD when renal injury was initiated. Mouse proximal tubule cells (mProx24) were used to clarify the role of AMPK. Feeding mice with HFD for 12 wk induced insulin resistance and kidney injury such as albuminuria, glomerulosclerosis, tubular injury, and inflammation, which were effectively inhibited by fenofibrate. In addition, fenofibrate treatment resulted in the activation of renal AMPK, upregulation of fatty acid oxidation (FAO) enzymes and antioxidants, and induction of autophagy in the HFD mice. In mProx24 cells, fenofibrate activated AMPK in a concentration-dependent manner, upregulated FAO enzymes and antioxidants, and induced autophagy, all of which were inhibited by treatment of compound C, an AMPK inhibitor. Fenofibrate-induced autophagy was also significantly blocked by AMPKα1 siRNA but not by PPARα siRNA. Collectively, these results demonstrate that delayed treatment with fenofibrate has a therapeutic effect on HFD-induced kidney injury, at least in part, through the activation of AMPK and induction of subsequent downstream effectors: autophagy, FAO enzymes, and antioxidants.

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.