The Application of Knowledge-Based Clinical Decision Support Systems to Detect Antibiotic Allergy.

Prevention of drug allergies is important for patient safety. The objective of this study was to evaluate the outcomes of antibiotic allergy-checking clinical decision support system (CDSS), K-CDSTM. A retrospective chart review study was performed in 29 hospitals and antibiotic allergy alerts data were collected from May to August 2022. A total of 15,535 allergy alert cases from 1586 patients were reviewed. The most frequently prescribed antibiotics were cephalosporins (48.5%), and there were more alerts of potential cross-reactivity between beta-lactam antibiotics than between antibiotics with the same ingredients or of the same class. Regarding allergy symptoms, dermatological disorders were the most common (38.8%), followed by gastrointestinal disorders (28.4%). The 714 cases (4.5%) of immune system disorders included 222 cases of anaphylaxis and 61 cases of severe cutaneous adverse reactions. Alerts for severe symptoms were reported in 6.4% of all cases. This study confirmed that K-CDS can effectively detect antibiotic allergies and prevent the prescription of potentially allergy-causing antibiotics among patients with a history of antibiotic allergies. If K-CDS is expanded to medical institutions nationwide in the future, it can prevent an increase in allergy recurrence related to drug prescriptions through cloud-based allergy detection CDSSs.

Sodium-glucose cotransporter-2 inhibitors and their potential role in dementia onset and cognitive function in patients with diabetes mellitus: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to determine the association between the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and dementia onset as well as cognitive function in patients with diabetes mellitus. We comprehensively searched the MEDLINE, Embase, and CENTRAL databases to select relevant studies published up to August 2023. The use of SGLT-2 inhibitors significantly lowers dementia risk compared to SGLT-2i non-users (Hazard ratio: 0.68, 95 % CI: 0.50-0.92). Furthermore, our findings indicated a positive effect of SGLT-2 inhibitor use on cognitive function score improvement, as demonstrated by the standardized mean difference of 0.88 (95 % CI: 0.32-1.44), particularly among populations with mild cognitive impairment or dementia. This systematic review and meta-analysis indicate a potential role of SGLT-2 inhibitors in reducing the risk of dementia in patients with diabetes mellitus. These findings underscore the need for well-controlled large clinical trials and future research in this field.

Intracoronary antithrombotic therapy during primary percutaneous coronary intervention in patients with STEMI: A systematic review and network meta-analysis.

INTRODUCTION: The efficacy of intracoronary (IC) antithrombotic therapy, which may best prevent the no-reflow phenomenon during percutaneous coronary intervention (PCI), remains unclear. Therefore, we compared the efficacy and safety of different IC antithrombotic agents. MATERIALS AND METHODS: This systematic review and network meta-analysis of randomized controlled trials (RCTs) compared IC fibrinolytic agents (recombinant tissue plasminogen activators [rtPAs] and non-rtPAs) or glycoprotein IIb/IIIa inhibitors (small molecules and monoclonal antibodies) with placebo by searching the relevant studies published before September 21, 2022. Bayesian network meta-analyses were performed using random-effects models. RESULTS: Twenty-five RCTs with 4546 patients were included. Non-rtPAs and small molecules were significantly more effective in achieving thrombolysis in myocardial infarction (TIMI) grade 3 flow than placebo (odds ratio [OR] 2.28, 95 % credible intervals [CrI] 1.24-4.13; OR 2.06, 95 % CrI 1.17-3.46). Moreover, these agents' efficacy was observed in other microcirculation-related outcomes, including TIMI myocardial perfusion grade 3, complete ST-segment resolution, and corrected TIMI frame counts. Within 6 months, small molecules were associated with both an improved left ventricular ejection fraction (MD 3.90, 95 % CrI 0.48-7.46) and major adverse cardiac events (MACE) reduction (OR 0.36, 95 % CrI 0.20-0.61). Non-rtPAs demonstrated a reduced MACE incidence within 6 months (OR 0.51, 95 % CrI 0.31-0.81). The results were consistent in the subgroup with a total ischemic time > 6 h. No significant differences in mortality or bleeding events were observed. CONCLUSIONS: IC non-rtPAs and small molecules may be effective for adjunctive therapy to PCI, particularly in patients with longer ischemia periods.

Association between selective serotonin reuptake inhibitor use and developing irritable bowel syndrome through retrospective analysis.

BACKGROUND AND AIM: Serotonin affects the balance and integrity of the gut microbiome; however, studies have confirmed the influence of selective serotonin reuptake inhibitors (SSRIs) on irritable bowel syndrome (IBS). We evaluated the association between SSRI use and subsequent IBS occurrence in a real-world setting. METHODS: A multivariate Cox proportional hazard model was adopted, and the National Health Insurance Service cohort claims database between 2010 and 2019 was used. Non-SSRI users were selected using the propensity score matching method. Subgroup analyses were performed using the point of use, cumulative dose, and duration of SSRI use. Additional analysis was performed using a control group without psychiatric medications. RESULTS: We included 2901 SSRI users and 2727 non-SSRI users. After adjusting covariates, the risk of developing IBS in SSRI users was 1.54 times that in non-SSRI users (95% confidence interval [CI]: 1.01-2.33). The hazard ratio (HR) of the recent, heavy, and short-term user groups were 3.19 (95% CI: 2.03-4.99), 2.22 (95% CI: 1.50-3.29), and 4.83 (95% CI: 3.02-7.73), respectively, compared with that of non-users. In patients without a history of psychiatric medications, the risk of IBS incidence after SSRI use increased significantly (HR: 1.61, 95% CI: 1.06-2.42), whereas HR was insignificant in patients with a history of psychiatric medications (HR: 1.25, 95% CI: 0.98-1.60). CONCLUSIONS: The risk of subsequent IBS occurrence following SSRI use was high in patients who initially took a heavy SSRI dose and those who did not have a history of psychiatric drug use.

Aneurysm and Artery Dissection After Oral VEGFR-TKI Use in Adults With Cancer.

Importance: The association of tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR-TKIs) with aneurysm and artery dissection (AAD) has been frequently reported in spontaneous reporting databases. Objective: To investigate the risk and incidence of AAD occurrence in patients with cancer treated with oral VEGFR-TKIs, with capecitabine as an active comparator. Design, Setting, and Participants: This national, historical cohort study was conducted using national claims data from the National Health Insurance Service in Korea from 2007 to 2020, with a 1-year follow-up. Patients with cancer aged 40 years or older prescribed oral VEGFR-TKIs or capecitabine were enrolled. Data were analyzed from September 2022 through April 2023. Exposure: Oral VEGFR-TKIs (sorafenib, regorafenib, vandetanib, sunitinib, lenvatinib, axitinib, and pazopanib) or capecitabine as a comparator. Main Outcomes and Measures: Hazard ratios (HRs) were used to investigate the association between VEGFR-TKI use and AAD after propensity score matching. The primary outcome was AAD, and secondary outcomes were aortic aneurysm and dissection and AAD with rupture. Outcomes were defined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes. Results: Among 127 710 patients with cancer eligible for the study (80 386 males [62.9%]; mean [SD] age, 62.6 [10.9] years), 37 308 patients received VEGFR-TKIs and 90 402 patients received capecitabine. Among 27 535 matched patients receiving VEGFR-TKIs, the incidence of AAD within 1 year of treatment initiation was 6.0 per 1000 person-years. The median (IQR) time to AAD onset in the matched AAD group was 114 (67-257) days after treatment initiation, with the highest incidence observed during the first 3 months (45 incidents vs 31, 17, and 16 incidents during 3- to 6-month, 6- to 9-month, and 9- to 12-month periods, respectively). Cox regression modeling showed that the risk of AAD occurrence was significantly higher among patients prescribed VEGFR-TKIs than those receiving capecitabine (HR, 1.48; 95% CI, 1.08-2.02); similar results were obtained among females (HR, 2.08; 95% CI, 1.26-3.42), older adults (aged ≥65 years; HR, 1.42; 95% CI, 1.01-1.99), and patients with dyslipidemia (HR, 1.58; 95% CI, 1.11-2.24). Conclusions and Relevance: In this study, the use of oral VEGFR-TKIs was associated with an increased risk of AAD occurrence. These findings elucidate vascular toxic effects and may provide a substantial reference for reducing the socioeconomic burden of adverse events associated with VEGFR-TKI use.

An indirect comparison of efficacy including histologic assessment and safety in biologic therapy in ulcerative colitis: Systemic review and network meta-analysis.

BACKGROUNDS AND AIMS: There are currently no studies comparing histologic remission of FDA-approved biologics for moderate to severe ulcerative colitis (UC), except for one head-to-head VARSITY trial. The current study employs a network meta-analysis to compare the efficacy, including histologic remission and safety of biologic agents for UC. METHODS: Using four electronic databases, including Pubmed, EMBASE, The Cochrane Library, and ClinicalTrials.gov, a search was conducted of all literature published until September 2022. Included were studies of randomized controlled trials with adult patients with moderate to severe UC using biologics approved by the FDA. An odd ratio with a 95 percent credible interval and ranking information was calculated for each endpoint. RESULTS: The results of the network meta-analysis did not reveal statistically significant differences among biological agents. However, the ranking information for each biological agent exhibited the following patterns. Vedolizumab was ranked first for overall efficacy endpoints in the maintenance phase, including histologic remission. Except for histologic remission, Ustekinumab was identified as the top-ranked drug for induction phase efficacy endpoints other than histologic remission. Adalimumab was identified as the top-ranked drug for maintenance phase corticosteroid-free remission. Vedolizumab was identified as the top-ranked drug in the induction phase for Treatment Emergent Adverse Events (TEAE). Adalimumab was identified as the top-ranked drug in the induction phase for infection. For TEAE and infection in the maintenance phase and Treatment Emergent Severe Adverse Events (TESAE) in both the induction and maintenance phases, Ustekinumab was determined to be the top-ranked medication. CONCLUSIONS: Including histologic remission, for the overall efficacy endpoints in the maintenance phase, VDZ was identified as the first rank drug, but there was no statistically significant difference between biologics. Therefore, the generalization of the results of this study is bounded due to the intrinsic limitations of the study provided.

Vitamin D supplementation for depression in older adults: a meta-analysis of randomized controlled trials.

Background: In older adults, depression is associated with several other clinical problems such as cognitive impairment and low quality of life. Several studies have evaluated the relationship between vitamin D and depression in older adults; however, the results have been controversial thus far. Objective: This study aimed to investigate the effects of vitamin D supplementation on depressive symptom improvement among individuals aged ≥60 years with or without a diagnosis of depression or depressive symptoms based on a meta-analysis of randomized controlled trials (RCTs). Methods: RCTs were identified to analyze the relationship between vitamin D supplementation and depressive symptoms. MEDLINE, CENTRAL, Embase, and PsycINFO were systematically searched for relevant articles published from inception to November 2022. RCTs that evaluated the effect of vitamin D supplementation in participants aged ≥60 years compared to placebo were included. A random effects model was used in this meta-analysis because of the differences between the included RCTs. The quality of the RCTs was assessed using Risk of Bias 2. Results: Seven trials were included in the analyses. The primary outcome of pre-post score changes included five trials with a total of 752 participants. The secondary outcome of post-intervention score included all seven trials with a total of 4,385 participants. No significant improvement in depressive symptoms in either pre-post score changes [standardized mean difference (SMD) = -0.49; 95% confidence interval (CI) -1.07-0.09; p = 0.10] or post-intervention score (SMD = -0.10; 95% CI -0.28-0.07; p = 0.25) was found. Conclusion: Vitamin D supplementation in older adults was not associated with an improvement in depressive symptoms. More studies in older adults are needed to evaluate the association between vitamin D supplementation and depression.

Intracoronary versus intravenous glycoprotein IIb/IIIa inhibitors during primary percutaneous coronary intervention in patients with STEMI: a systematic review and meta-analysis.

BACKGROUND: Intracoronary (IC) administration of glycoprotein IIb/IIIa inhibitors (GPIs) has been studied as an adjunctive therapy to improve outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of IC administration of GPIs compared with those of intravenous (IV) administration in patients with STEMI. METHODS: We searched the MEDLINE, Embase, and Cochrane CENTRAL databases for relevant studies published before September 21, 2022. In total, 22 randomized controlled trials involving 7,699 patients were included. RESULTS: The proportions of patients achieving thrombolysis in myocardial infarction grade 3 flow, myocardial blush grade 2/3, and complete ST-segment resolution were significantly higher in the IC group than in the IV group. Major adverse cardiac events (MACE) (RR: 0.54, 95% CI: 0.37-0.80) and heart failure (RR: 0.48, 95% CI: 0.25-0.91) within 1 month were significantly lower in the IC group than in the IV group; however, after 6 months, no difference was observed in MACE risk. Additionally, the risks of death and bleeding did not differ between the two routes of administration. CONCLUSIONS: When considering adjunctive GPI administration for patients with STEMI, the IC route may offer greater benefits than the IV route in terms of myocardial reperfusion and reduced occurrence of MACE and heart failure within 1 month. Nonetheless, when making decisions for IC administration of GPIs, the absence of a benefit for bleeding risk and difficulty accessing the administration route should be considered.

Effect of Pharmacist-Led Intervention in Elderly Patients through a Comprehensive Medication Reconciliation: A Randomized Clinical Trial.

PURPOSE: Polypharmacy can cause drug-related problems, such as potentially inappropriate medication (PIM) use and medication regimen complexity in the elderly. This study aimed to investigate the feasibility and effectiveness of a collaborative medication review and comprehensive medication reconciliation intervention by a pharmacist and hospitalist for older patients. MATERIALS AND METHODS: This comprehensive medication reconciliation study was designed as a prospective, open-label, randomized clinical trial with patients aged 65 years or older from July to December 2020. Comprehensive medication reconciliation comprised medication reviews based on the PIM criteria. The discharge of medication was simplified to reduce regimen complexity. The primary outcome was the difference in adverse drug events (ADEs) throughout hospitalization and 30 days after discharge. Changes in regimen complexity were evaluated using the Korean version of the medication regimen complexity index (MRCI-K). RESULTS: Of the 32 patients, 34.4% (n=11/32) reported ADEs before discharge, and 19.2% (n=5/26) ADEs were reported at the 30-day phone call. No ADEs were reported in the intervention group, whereas five events were reported in the control group (p=0.039) on the 30-day phone call. The mean acceptance rate of medication reconciliation was 83%. The mean decreases of MRCI-K between at the admission and the discharge were 6.2 vs. 2.4, although it was not significant (p=0.159). CONCLUSION: As a result, we identified the effect of pharmacist-led interventions using comprehensive medication reconciliation, including the criteria of the PIMs and the MRCI-K, and the differences in ADEs between the intervention and control groups at the 30-day follow-up after discharge in elderly patients. TRIAL REGISTRATION: (Clinical trial number: KCT0005994).

Neuroprotective effect of angiotensin II receptor blockers on the risk of incident Alzheimer's disease: A nationwide population-based cohort study.

Background: Recent studies on renin-angiotensin system (RAS) inhibitors have reported a reduced risk of Alzheimer's disease (AD). Nevertheless, the effect of RAS inhibitor type and blood-brain barrier (BBB) permeability on the risk of AD is still unknown. Objectives: To assess the effects of RAS inhibitors on the risk of AD based on the type and BBB permeability and investigate the cumulative duration-response relationship. Methods: This was a population-based retrospective cohort study using the Korean Health Insurance Review and Assessment database records from 2008 to 2019. The data of patients diagnosed with ischemic heart disease between January 2009 and June 2009 were identified for inclusion in the analyses. Propensity score matching was used to balance RAS inhibitor users with non-users. The association between the use of RAS inhibitors and incident AD was evaluated using a multivariate Cox proportional hazard regression model. The results are presented in adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Results: Among the 57,420 matched individuals, 7,303 developed AD within the follow-up period. While the use of angiotensin-converting enzyme inhibitors (ACEIs) was not significantly associated with AD risk, the use of angiotensin II receptor blockers (ARBs) showed a significant association with reduced risk of incident AD (aHR = 0.94; 95% CI = 0.90-0.99). Furthermore, the use of BBB-crossing ARBs was associated with a lower risk of AD (aHR = 0.83; 95% CI = 0.78-0.88) with a cumulative duration-response relationship. A higher cumulative dose or duration of BBB-crossing ARBs was associated with a gradual decrease in AD risk (P for trend < 0.001). No significant association between the use of ACEIs and the risk of AD was observed regardless of BBB permeability. Conclusion: Long-term use of BBB-crossing ARBs significantly reduced the risk of AD development. The finding may provide valuable insight into disease-modifying drug options for preventing AD in patients with cardiovascular diseases.

Risk of major adverse events associated with gabapentinoid and opioid combination therapy: A systematic review and meta-analysis.

Background: The use of opioid-gabapentinoid combinations has increased, raising several safety concerns. However, meta-analysis studies focusing on this issue are limited. Objective: To evaluate the risk of central nervous system (CNS) depression, gastrointestinal (GI) adverse events, and mortality of combination therapy compared with those of opioid therapy and to explore the differences in the results according to study design and indications. Methods: Relevant studies were selected (published before 30 January 2022) by searching the MEDLINE, Embase, and CENTRAL databases. The pooled odds ratios (OR) with 95% confidence intervals (CI) of the outcomes were estimated using the Mantel-Haenszel method. Subgroup and meta-regression analyses were performed according to study characteristics. Quality assessment was conducted using the Risk of Bias 2 tool for randomized controlled trials (RCTs) and Cochrane Collaboration's Risk of Bias in non-RCTs tool for non-randomized trials. Results: Adverse events were reported in 26 RCTs and 7 non-RCTs, and mortality was reported in 10 non-RCTs. Compared to opioid therapy, dizziness, cognitive dysfunction, and respiratory depression in combination therapy significantly increased in non-RCTs (OR 3.26, 95% CI 1.82-5.85; OR 3.13, 95% CI 1.51-6.50; OR 1.71, 95% CI 1.31-2.24, respectively), and a similar trend for dizziness and cognitive dysfunction was also identified in the RCT analysis, although the difference was not significant. Combination therapy for cancer pain was associated with the highest risk of sedation in subgroup analysis. Combination therapy significantly decreased the risk of GI adverse events, including nausea, vomiting, and constipation. The mortality risk associated with combination therapy was higher than that associated with opioid therapy (OR 2.76, 95% CI 1.26-6.05). Conclusion: Opioid-gabapentinoid combination therapy could be associated with an increased risk of CNS depression and mortality, despite tolerable GI adverse events. These data suggest that combination therapy requires close monitoring of CNS depression, especially in cancer patients. Caution is needed in interpreting the clinical meanings owing to the lack of risk difference in respiratory depression in the RCT-only analysis and the absence of RCT or prospective studies investigating mortality.

Prevalence and patterns of the concurrent use of anticholinergics for the motor symptoms of Parkinson's disease and acetylcholinesterase inhibitors in Parkinson's disease patients with dementia: a cross-sectional study using Korea National Health Insurance claims data.

BACKGROUND: The concurrent use of anticholinergics and acetylcholinesterase inhibitors (ACHEIs) in Parkinson's disease (PD) patients with dementia should be avoided because the opposing pharmacological actions of both drugs reduce the treatment efficacy. We aimed to investigate the prevalence of the concurrent use of these two types of drugs in Korean patients. METHODS: In the 2017 Health Insurance Review and Assessment Service-National Aged Patient Sample data, comprising insurance claims records for a 10% random sample of patients aged ≥ 65 years in Korea, "concurrent use" was defined as the overlapping of anticholinergic and ACHEI doses for at least 2 months. RESULTS: Among 8,845 PD patients with dementia, 847 (9.58%) were co-administered anticholinergics, used to treat the motor symptoms of PD, and ACHEIs for a mean duration of 7.7 months. A total of 286 (33.77% of all co-administered) patients used both drug types concurrently all year. About 80% of concurrent users were prescribed each drug by the same prescriber, indicating that coadministration may not be due to a lack of information sharing between providers. Logistic regression analysis showed that patients mainly treated at clinics (odds ratio (OR), 1.541; 95% confidence interval (CI), 1.158-2.059), hospitals (OR, 2.135; 95% CI, 1.586-2.883), and general hospitals (OR, 1.568; 95% CI, 1.221-2.028) were more likely to be co-prescribed anticholinergics and ACHEIs than those mainly treated at tertiary-care hospitals. PD patients with dementia treated at healthcare organizations located in areas other than the capital city had an approximately 22% higher risk of concurrent use (OR: 1.227, 95% CI: 1.046-1.441). CONCLUSIONS: The concurrent use of anticholinergics for the motor symptoms of PD and ACHEIs in elderly Korean PD patients with dementia cannot be ignored, and strategies that mitigate potentially inappropriate concurrent drug use are required.

Trends in potentially inappropriate opioid prescribing and associated risk factors among Korean noncancer patients prescribed non-injectable opioid analgesics.

Introduction: The aim of this study was to investigate trends in the prevalence of potentially inappropriate opioid prescribing (PIOP) and identify potential risk factors among Korean noncancer patients. Methods: We conducted a cross-sectional study of annual national patient sample data from the Korean Health Insurance Review and Assessment Service (HIRA-NPS) for the period 2012-2018. Noncancer patients who were prescribed non-injectable opioid analgesics (NIOAs) at least once were included. The proportion of patients with at least one PIOP in terms of concurrent use of benzodiazepines or gabapentinoids, substance use disorder, treatment duration, and dosage was evaluated. Multivariable logistic regression was performed to identify the risk factors associated with PIOP. Results: Of the 9,772,503 noncancer patients, 1,583,444 (16.2%) were prescribed NIOAs at least once. Among them, 15.7% were exposed to PIOP, and the prevalence was much higher (31.6%) in the elderly group (age: ⩾65 years). The prevalence of PIOP increased 1.1-fold over 7 years (14.8-16.8%) among the total NIOA users and was more pronounced in non-tramadol NIOA users (a 1.5-fold increase, from 13.2% to 19.4%). Multivariable logistic regression indicated that older age, beneficiaries of medical aid or national meritorious service, exposure to polypharmacy, psychological disorder, chronic pain indication, and concomitant sedative use were independently associated with higher odds of PIOP. Discussion and Conclusion: We found that the prevalence of PIOP was 15.7% among Korean noncancer patients, and it increased over the 7-year study period. This increasing trend is alarming because it was more drastic with non-tramadol NIOAs compared with that with tramadol. Several patient-level risk factors associated with PIOP would be useful in targeted management strategies for the safe use of opioids. Plain Language Summary: Potentially inappropriate opioid prescribing and related risk factors among noncancer patients prescribed non-injectable opioids in Korea In Korea, the prevalence of non-injectable opioid analgesic (NIOA) use in noncancer patients steadily increased from 15.3% in 2012 to 17.1% in 2018.Also, the prevalence of potentially inappropriate opioid prescribing (PIOP) increased from 14.8% in 2012 to 16.8% in 2018.The following factors were associated with a markedly increased risk of PIOP: age, beneficiaries of medical aid or national meritorious service, polypharmacy, psychological disorder, chronic pain, and concomitant medications.

Protective Effect of Renin-Angiotensin System Inhibitors on Parkinson's Disease: A Nationwide Cohort Study.

Background: Renin-angiotensin system (RAS) inhibitors have been suggested as protective agents in Parkinson's disease (PD). However, epidemiological evidence on the association between RAS inhibitors and the development of PD is inconsistent. Objectives: To investigate the effect of RAS inhibitors on PD risk in patients with ischemic heart disease (IHD) by type and cumulative duration of RAS inhibitors and their degree of blood-brain barrier (BBB) penetration ability. Methods: This was a propensity score-matched retrospective cohort study using 2008-2019 healthcare claims data from the Korean Health Insurance Review and Assessment database. The association between RAS inhibitor use and PD in patients with IHD was evaluated using multivariate Cox proportional hazard regression analysis. The risks are presented as adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Results: Over a 10-year follow-up, 1,086 of 62,228 IHD patients developed PD. The Cox regression model showed that the use of RAS inhibitors was significantly associated with a lower risk of PD (aHR = 0.75; 95% CI 0.66-0.85) than the non-use of RAS inhibitors. Specifically, this reduced risk of PD only remained with the use of BBB-crossing angiotensin II receptor blockers (ARBs) (aHR = 0.62; 95% CI = 0.53-0.74), and this association was more definite with an increasing cumulative duration. A significantly reduced risk of PD was not observed with the use of BBB-crossing angiotensin-converting enzyme inhibitors. Conclusions: The use of ARBs with BBB-penetrating properties and a high cumulative duration significantly reduces the risk of PD in IHD patients. This protective effect could provide insight into disease-modifying drug candidates for PD.

Improvement in Medication Adherence after Pharmacist Intervention Is Associated with Favorable Clinical Outcomes in Patients with Ulcerative Colitis.

Background/Aims: Although pharmacist intervention for patients with chronic diseases has been shown to improve medication adherence, few studies have evaluated its effects on the objective clinical outcomes. We investigated the impact of pharmacist intervention on medication adherence and clinical outcomes in patients with ulcerative colitis (UC). Methods: Patients with UC and low medication adherence were divided into two groups, based on pharmacist intervention. Their medication possession ratio and nonadherence rate for 6 months before and after the baseline were investigated. The partial Mayo score, flare-up incidence, and factors influencing flare-up events for 1 year after the baseline were analyzed. Results: Of 99 patients, 33 and 66 were included in the intervention and control groups, respectively. The nonadherence rate significantly declined in the intervention group 6 months after the baseline (60.6% before vs 30.3% after; p=0.013). The groups showed a significant difference regarding time-related partial Mayo scores (p=0.002). Intervention was significantly negatively correlated with time and the partial Mayo score (r2=0.035, p=0.013). A significant difference was observed in the flare-up incidence (33.3% in the intervention group vs 54.6% in the control group; p=0.046). Multivariate logistic regression indicated that pharmacist intervention (adjusted odds ratio, 0.370; 95% confidence interval, 0.145 to 0.945; p=0.038) independently reduced the flareup risk. Conclusions: Pharmacist intervention significantly decreased the nonadherence rate, improved the partial Mayo score, and reduced the flare-up incidence compared with the control group in a cohort of UC patients identified to have low medication adherence.

Efficacy and Safety of Clinically Driven Low-Dose Treatment with Direct Oral Anticoagulants in Asians with Atrial Fibrillation: a Systematic Review and Meta-analysis.

PURPOSE: Although clinically driven low-dose (CDLD) treatment with direct oral anticoagulants (DOACs) is frequently administered to Asian patients with atrial fibrillation, clinical evidence confirming its efficacy remains insufficient. We evaluated the clinical efficacy and safety of CDLD treatment with DOACs compared to on-label dose treatment in Asian patients with atrial fibrillation and assessed the differences in the baseline characteristics between patients receiving these treatments. METHODS: We searched the MEDLINE, CENTRAL, EMBASE, Web of Science, and Scopus databases for articles from inception through July 2020. RESULTS: Thirteen studies were included in this meta-analysis. The baseline characteristics of the CDLD group were significantly different from those of the standard dose (STD) and standard low-dose (SLD) groups. The incidences of thromboembolic events (risk ratio [RR] 0.46, 95% confidence interval [CI] 0.29-0.73, p < 0.001) and major bleeding (RR 0.55, 95% CI 0.35-0.87, p = 0.01) in the CDLD group were lower than those in the SLD group; however, they were comparable with those in the STD group. The incidence of a composite endpoint in the CDLD group was not significantly different from that in the STD group but was significantly lower than that in the SLD group (RR 0.50, 95% CI 0.38-0.65, p < 0.001). CONCLUSION: The clinical outcomes of CDLD treatment showed no difference compared to those of the STD treatment despite the vulnerable baseline characteristics of the CDLD group for thromboembolic and major bleeding events.

Efficacy and tolerability of infliximab retreatment in patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: A large proportion of patients with inflammatory bowel disease (IBD) relapse after drug discontinuation despite achieving a stable state of infliximab-induced clinical remission. Resuming the use of the same tumor necrosis factor-alpha (TNF-α) inhibitors in patients who relapse following TNF-α inhibitor discontinuation was suggested as a treatment strategy. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of infliximab retreatment in patients with IBD. METHODS: A systematic literature search to shortlist relevant studies was conducted using the MEDLINE, Embase, CINAHL, and SCOPUS databases for studies published from inception to August 2020. RESULTS: Nine studies were included in the meta-analysis. The pooled clinical remission rate of infliximab retreatment in patients with IBD was 85% (95% confidence interval (CI), 81-89%) for induction treatment and 73% (95% CI, 66-80%) for maintenance treatment. A clinical remission rate following infliximab reintroduction was achieved in a greater proportion of patients with Crohn's disease (87%; 95% CI, 83-91%) than in those with ulcerative colitis (78%; 95% CI, 61-91%) for induction treatment, but the difference was not statistically significant. Infusion-related reactions after infliximab retreatment occurred in 9% of patients with IBD (95% CI, 3-16%). CONCLUSION: Infliximab retreatment showed high clinical remission rates with tolerable infusion-related reactions in patients with IBD who achieved remission with initial infliximab treatment but relapsed after its discontinuation. We suggest infliximab as a viable alternative in patients with IBD who previously responded well to infliximab treatment.

Interrupted Time Series Analysis of Changes in Zolpidem Use Due to Media Broadcasts.

Media has become a major source of information on health and plays a role in the decision-making process on health topics. We aimed to evaluate the association between zolpidem use and media broadcasts that reported the suicide risk. We obtained the data of adult outpatients who have been prescribed zolpidem or other hypnotics from the National Patient Sample database (2015-2017). We evaluated the change in zolpidem or other hypnotic prescription trends based on the prescription rate and average daily prescribed dose before and after July 2016, using interrupted time series analysis. A total of 129,787 adult patients had at least one zolpidem prescription in 3 years. The prescription rate of zolpidem after the broadcast decreased significantly by 0.178% (95% confidence interval (CI): -0.214, -0.142), whereas that of other hypnotic users did not differ from that before the broadcast (-0.020%, 95% CI: -0.088, 0.047). However, the trends in the prescription rate before and after the broadcast did not differ for zolpidem and other hypnotics. Broadcasting medication safety through major public media could have an effect on medication use. After broadcasting about the suicide risk of zolpidem, its overall prescription rate decreased immediately, but the trend was not changed.

Assessing the effects of National Health Insurance reimbursement policy revisions for anti-osteoporotic drugs in Korean women aged 50 or older.

INTRODUCTION: The Korean National Health Insurance revised its reimbursement criteria to expand coverage for anti-osteoporotic drug treatments in 2011 (expanding diagnostic criteria and the coverage period for anti-osteoporotic therapy) and 2015 (including osteoporotic fracture patients regardless of bone mineral density). We examined whether the two revisions contributed to an increase in the prescription rates of anti-osteoporotic drugs in Korea. METHODS: We used the Health Insurance Review and Assessment Service-National Patient Sample data from 2010 through 2016. A segmented regression analysis of interrupted time series was performed to assess changes in the monthly prescription rates of anti-osteoporotic drugs among women aged 50 or older, defined as the proportion of elderly women prescribed with anti-osteoporotic drugs. RESULTS: Both the levels (i.e., abrupt jump or drop) and the trends (i.e., slope) of the prescription rates of anti-osteoporotic drugs in the general population, osteoporotic patients, and osteoporotic fracture patients showed no significant changes after the first revision. However, there was a significant increase in the trends in the general population (ß = 0.0166, p = 0.0173) and in osteoporotic patients (ß = 0.1128, p = 0.0157) after the second revision. Women aged 65 to 79 years were the most significantly increased group in terms of the treatment proportion after the second revision because the trend was significant after the second revision in all three study populations (ß = 0.0300, 0.1212, 0.1392, respectively; p < 0.05). CONCLUSIONS: Although the two revisions expanded reimbursement coverage, only the second revision on reimbursing based on osteoporotic fracture regardless of bone mineral density was associated with increasing the proportion of post-menopausal women being treated with anti-osteoporotic drugs.

Trimetazidine Use and the Risk of Parkinsonism: A Nationwide Population-Based Study.

An association between trimetazidine (TMZ), an anti-anginal drug, and parkinsonism has been reported in a number of studies. However, evidence from studies with long-term follow-up and better validity is lacking. We investigated the risk of TMZ-associated parkinsonism, specifically the incidence rate, cumulative dose-response relationship, and combined effects with other parkinsonism-inducing medications. This propensity score-matched retrospective cohort study was conducted using 14-year health insurance claims data in South Korea. The risk of parkinsonism was evaluated using multivariate Cox proportional hazard regression analysis, adjusted for comorbidities and concurrent medications. A total of 9712 TMZ users and 29,116 matched non-TMZ users were included. TMZ users had a significantly higher incidence rate of parkinsonism than non-TMZ users (9.34 vs. 6.71 per 1000 person-years; p < 0.0001). TMZ use significantly increased the risk of parkinsonism (adjusted hazard ratio = 1.38; 95% confidence interval = 1.26-1.51). Increased risks were observed with accumulated doses of TMZ, as well as concurrent use of other parkinsonism-inducing medications. The findings indicate that TMZ use significantly increases the risk of parkinsonism in the South Korean population. Closer monitoring should be considered for TMZ users, especially for those who are older, using TMZ at high cumulative doses and other parkinsonism-inducing medications.