Comparative effects of glucose-lowering agents on endothelial function and arterial stiffness in patients with type 2 diabetes: A network meta-analysis.

BACKGROUND AND AIMS: Despite accumulating evidence on the potential of glucose-lowering agents (GLAs) to prevent cardiovascular events, the comparative effects of GLAs on vascular function remain unclear. This study utilized validated indicators such as flow-mediated dilation (FMD; positive value favors) and pulse wave velocity (PWV; negative value favors) to uncover the comparative effects of GLAs on vascular function. METHODS: Randomized controlled trials (RCTs) comparing the effects of GLAs on FMD or PWV with placebo or other GLAs in patients with type 2 diabetes (T2DM) were searched through PubMed and Embase. The frequentist method of network meta-analysis (NMA) was conducted using a random effects model, and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. RESULTS: The NMA included 38 RCTs with 2,065 patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium glucose cotransporter-2 inhibitors (SGLT-2Is) had significantly more positive effects on FMD improvement and PWV reduction than placebo. Thiazolidinedione (TZD) treatment resulted in significantly improved FMD compared to other GLAs as well as placebo (SMD: 1.14; 95% CI: 0.84 to 1.43). Both pioglitazone and rosiglitazone were discovered to have considerably more favorable effects on improving FMD and reducing PWV compared to placebo and other GLAs, as a result of the analysis incorporating each drug in the TZD class. The sensitivity analysis results corroborated the main findings. CONCLUSIONS: This NMA showed more favorable effects of GLP-1RAs and SGLT-2Is than placebo in improving both arterial stiffness and endothelial function in patients with T2DM. In addition, TZDs showed superior effects in improving endothelial function as compared with the other GLAs and placebo.

Association Between Migraine and Gastrointestinal Disease in Pediatric Patients: A Propensity Score Weighting Approach.

Purpose: Migraine is a neurological disorder affecting pediatric patients of all age groups, with a prevalence ranging from approximately 5% to 15%. It significantly impacts the quality of life in children and adolescents, potentially hampering their learning abilities, school performance, and daily activities. This study investigated the association between migraine and several prevalent gastrointestinal (GI) diseases in pediatric patients. Patients and Methods: We analyzed the Health Insurance Review and Assessment Service Pediatric Patient Sample (HIRA-PPS) dataset from South Korea. Propensity scores based on patient characteristics (age, sex, and insurance type) were employed through the inverse probability of treatment weighting (IPTW) in binary logistic regression. We included gastroesophageal disease (GERD), peptic ulcer disease (PUD), gastritis, dyspepsia, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) as GI diseases. Results: A total of 683,347 patients from the HIRA dataset were included in the study. After IPTW adjustment, the prevalence of GI diseases among pediatric patients with migraine remained significantly increased (OR 4.15; 95% CI 4.12-4.18). Migraine patients showed higher prevalence rates for all six individual GI diseases, with GERD (OR 4.11; 95% CI 4.05-4.16) and IBS (OR 3.79; 95% CI 3.74-3.84) showing the highest associations. We also confirmed a progressively increasing association between the presence of diagnosed migraine and GI diseases. Conclusion: This study highlights a strong association between pediatric migraine and GI diseases, even after adjusting for patient characteristics. The elevated prevalence of various GI diseases in migraine patients suggests the need for comprehensive approaches to their prevention and treatment.

The In Vitro and In Vivo Anticancer Effect of Photomed for Photodynamic Therapy: Comparison with Photofrin and Radachlorin.

To overcome the limitation of conventional cancer treatments, photodynamic therapy (PDT) has been introduced as another treatment option. PDT provides a non-invasive, non-surgical way with reduced toxicity. To improve the antitumor efficacy of PDT, we synthesized a novel photosensitizer, a 3-substituted methyl pyropheophorbide-a derivative (Photomed). The purpose of the study was to evaluate the antitumor effect of PDT with Photomed comparing with the clinically approved photosensitizers Photofrin and Radachlorin. The cytotoxicity assay against SCC VII cells (murine squamous cell carcinoma) was performed to determine whether Photomed is safe without PDT and whether Photomed is effective against cancer cells with PDT. An in vivo anticancer efficacy study was also performed using SCC VII tumor-bearing mice. The mice were divided into small-tumor and large-tumor groups to identify whether Photomed-induced PDT is effective for not only small tumors but also large tumors. From in vitro and in vivo studies, Photomed was confirmed to be (1) a safe photosensitizer without laser irradiation, (2) the most effective photosensitizer with PDT against cancers compared to Photofrin and Radachlorin and (3) effective with PDT in treating not only small tumors but also large tumors. In conclusion, Photomed may contribute as a novel, potential photosensitizer for use in PDT cancer treatment.

Increased Risk of Anemia in Patients with Asthma.

Purpose: Asthma can cause a systemic inflammatory response, and anemia of chronic disease (ACD) is known to be caused by other disorders with a chronic inflammatory state. However, it is unclear whether the incidence of anemia is increased in patients with asthma. The objective of this study was to compare the incidence of anemia in patients with asthma and healthy adults. Patients and Methods: This retrospective cohort study included patients newly diagnosed with asthma at Seoul National University Hospital from 2010 to 2017. Patients with comorbidities before the first visit (index date) that may increase anemia risk were excluded. Cox regression models adjusting for patient age, sex, and obesity were used to compare anemia hazard ratios (HRs) between asthma patients (n=1354) and healthy adults (n=1731). Results: This study included 3085 patients. During 5-y follow-up, anemia occurred in 203 (15.0%) patients with asthma and 79 (4.6%) healthy adults. Compared with healthy adults, the HR for anemia after adjusting for age, sex, and obesity was 4.06 (95% CI: 2.70-6.09) in patients with asthma. In patients aged 18-64.9 y, the adjusted HR of anemia was 3.27 (95% CI: 2.12-5.04) in patients with asthma, compared to healthy patients. In patients >65 y, this adjusted HR was 5.56 (95% CI: 1.31-23.67). Conclusion: The risk of anemia was increased in patients with asthma after adjusting for sex, age, and obesity and excluding comorbidities that can cause anemia. These results suggest the need for regular monitoring for anemia in patients with asthma.

Association between Gastrointestinal Diseases and Migraine.

Migraine is a common disease worldwide, and recent studies showed that the incidence of migraine was increased in patients with gastrointestinal (GI) diseases. In addition, preclinical evidence suggested a bidirectional relationship between the GI nervous system and the central nervous system called the gut−brain axis. This study aimed to determine the association between several high-prevalence GI diseases and migraine. Patients diagnosed with migraine or GI diseases were classified as the patient group at least twice a year. We included peptic ulcer disease, dyspepsia, inflammatory bowel disease, irritable bowel syndrome, and gastroesophageal disease as GI diseases. A total of 781,115 patients from the HIRA dataset were included in the study. The prevalence of migraine was about 3.5 times higher in patients with one or more GI diseases after adjusting for age, gender, and insurance type (adjusted odds ratio (ORadj = 3.46, 95% CI: 3.30−3.63, p < 0.001). In addition, the prevalence of migraine was increased as the number of comorbid GI diseases increased. The prevalence of GI disease was also higher in patients with medication for migraine, both preventive and acute treatment, compared to patients with either acute preventive or acute treatment. There was a statistically significant association between the prevalence of GI diseases and migraine, and the higher the number of accompanying GI diseases, the higher the correlation was in patients using both preventive and acute treatment drugs for migraine.

Status of Medications Prescribed for Psychiatric Disorders in Korean Pediatric and Adolescent Patients.

While mental health services for children are increasing, few psychiatric drugs have been approved for such use. We analyzed claim data from 19,557 South Korean pediatric and adolescent patients (<20 years) who were diagnosed with schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, attention deficit-hyperactivity disorder (ADHD), or a tic disorder. Among these diseases, depressive episodes were the most common, followed by an anxiety disorder, ADHD, bipolar disorder, tic disorder, and schizophrenia. For each disease, prescriptions were categorized as full-label (approved indication with pediatric dosing in the package insert (PI)), partial-label (approved indication without pediatric dosing in the PI), and contraindication (contraindicated for the specific pediatric age in the PI). For schizophrenia, major depressive disorder, and anxiety disorder, more than 50% of the patients were prescribed partial-labeled medications. Additionally, more than 5% of patients with major depressive disorder were prescribed medications that were contraindicated for their age group. Our findings reveal that children with full-labeled psychiatric conditions are commonly administered drugs that are not explicitly approved for either their disease state or age, including off-label and unlicensed drugs. To use pharmaceuticals more safely, expanding drug indications using real-world data are needed.

A Knowledge, Attitude, and Practice Survey on Medication Safety in Korean Older Adults: An Analysis of an Ageing Society.

BACKGROUND: Older adults have certain limitations in acquiring and understanding information regarding medication safety. This study surveyed their medication habits and analysed the importance of relevant education to improve knowledge, attitudes, and practice (KAP). METHODS: Our survey included adults aged 65 years or older. We developed a questionnaire on medication safety based on the KAP model. To identify the interrelationships among KAP, we calculated the correlation coefficients using Pearson's correlation analysis. A t-test was performed to verify the differences in KAP associated with the respondents' medication safety education experience. RESULTS: We found that 79.4% of respondents self-administered their medications. Of the respondents, 28.2% had received medication safety education. Overall, the respondents had typical levels of knowledge, attitude responses, and behavioural practices associated with medication safety. The results showed significant differences between knowledge and practice; those who were educated on medication safety performed higher levels of safe practice than those who were not (p < 0.05). CONCLUSION: The KAP survey confirmed that knowledge about the safe use of medication positively affected older adults' attitudes and practices. To improve their medication usage habits, older adults should receive well-organised medication safety education.

Prevalence of Anemia in Pediatric Patients According to Asthma Control: Propensity Score Analysis.

PURPOSE: To investigate whether the degree of asthma control is associated with anemia in pediatric patients. PATIENTS AND METHODS: A cross-sectional study was performed using a dataset from the Health Insurance Reviews & Assessment Service (HIRA) of South Korea in 2016, which included children and adolescent patients diagnosed with asthma. Binary logistic regression was used to assess the association between asthma control and the prevalence of anemia. RESULTS: A total of 236,429 patients under 18 years old were included in the study, including 233,975 patients with controlled and 2454 with uncontrolled asthma. Binary logistic regression after adjustment for confounding factors showed that patients with uncontrolled asthma had a 2.64-fold higher prevalence of anemia than those with well-controlled asthma (OR = 2.64, 95% CI: 2.16-3.22). While there was no effect of gender on the results, there was a statistically significant association between the prevalence of anemia and asthma control in patients under 13 years old. CONCLUSION: These findings suggest that the prevalence of anemia is inversely correlated with asthma control in pediatric patients. Further studies are necessary to obtain pathophysiological insight into the relationship between severe inflammatory diseases and anemia.

Acid-suppressive agents and survival outcomes in patients with cancer: a systematic review and meta-analysis.

BACKGROUND: Patients with cancer often receive acid-suppressive agents (ASAs) to treat common gastroesophageal reflux and peptic ulcer diseases. Our systematic review addresses the association between ASAs and survival outcomes in these patients. METHODS: We searched MEDLINE, EMBASE, and Cochrane until December 2019, including randomized controlled trials (RCTs), quasi-RCTs, and observational studies concerning ASAs that reported progression-free survival (PFS) and/or overall survival (OS). We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) using the random-effects model, and assessed heterogeneity with I2 statistic. RESULTS: We included 45,626 patients from 7 RCTs and 18 observational studies, including esophageal/gastric, colorectal, pancreatic, lung, breast, prostate, kidney, and other cancers. Five studies showed that ASAs in lung cancer patients received tyrosine kinase inhibitors (TKIs) had significantly worse PFS (HR 1.64, 95% CI 1.14 - 2.37, I2 = 57%) and OS (HR 1.13, 95% CI 1.05 - 1.21, I2 = 0%) than nonusers. Each of five studies found no significant association between ASAs and OS in esophageal/gastric (HR 0.91, 95% CI 0.77 - 1.09, I2 = 32%) or colorectal cancer patients (HR 1.33, 95% CI 0.96- 1.85, I2 = 0%). ASAs were not significantly associated with an OS in patients with kidney cancer (HR 1.04, 95% CI 0.96 - 1.13, I2 = 28%). CONCLUSIONS: Meta-analysis showed that ASAs significantly associated with an increased mortality risk in lung cancer patients treated TKIs, but not in patients with esophageal/gastric, colorectal, or kidney cancer. Until further studies confirm these results, caution should be used when administering ASAs and TKIs to patients with lung cancer.

Domperidone prescribing patterns in pediatric patients before and after safety warning in South Korea.

OBJECTIVE: In 2014, the Korean Ministry of Food and Drug Safety (MFDS) issued a safety warning to carefully consider adverse cardiac effects when prescribing domperidone for children. We conducted this study to compare the trends of domperidone prescription in pediatrics before and after the MFDS safety warning. MATERIALS: This study included patients < 18 years old who used national health insurance services within the year 2011 and the year 2016, sampled from Health Insurance Review Agency data. METHODS: We analyzed domperidone prescribing patterns including prescribed daily dosage, maximum period of continuous prescription, and number and types of co-prescribed medications and compared two different years pre and post safety warning. RESULTS: A total of 16,614 pediatric patients (1.74%) received domperidone prescriptions in 2011, and 11,317 patients (1.23%) in 2016. The probability of receiving at least one prescription in 2016 has been reduced by 30% compared to 2011. Gastritis was the most common indication in both years. The number of prescriptions containing a maximum daily dosage of over 30 mg was significantly lower in 2016. In the same time period, the number of cases with a maximum continuous prescription period of more than 7 days significantly decreased (p < 0.001). In addition, from 2011 to 2016, comorbid diseases of domperidone-treated patients were similar, but the number of co-prescriptions of interacting medication to domperidone decreased (p < 0.001). CONCLUSION: After the 2014 safety letter was released, the pattern of prescribing domperidone in pediatrics has enhanced drug safety for children in terms of frequency of prescriptions, maximum duration of domperidone use, and the prescription of drugs interacting with domperidone.

Atopic Disease and Anemia in Korean Patients: Cross-Sectional Study with Propensity Score Analysis.

Atopic disease is associated with chronic inflammation, and anemia has been reported in patients with inflammatory disorders such as rheumatoid arthritis, chronic obstructive pulmonary disease, and irritable bowel disease. The objective of this study was to determine whether atopic disease is associated with an increased risk of anemia. A cross-sectional study with propensity score weighting was conducted using a health insurance review agency claims dataset comprised of randomized patients who used the Korean national health system at least once in 2016. The association between atopic disease (asthma, atopic dermatitis, allergic rhinitis) and anemia (iron deficiency anemia (IDA) and/or anemia of inflammation (AI)) was examined. A total of 1,468,033 patients were included in this study. The IDA/AI prevalence was 3.1% (45,681 patients). After propensity score weighting, there were 46,958 and 45,681 patients in the non-anemic and anemic groups, respectively. The prevalence of IDA/AI in patients with atopic dermatitis, allergic rhinitis, or asthma had an odds ratio (OR) of 1.40 (95% confidence interval (CI), 1.33-1.48; p < 0.001), 1.17 (95% CI, 1.14-1.21; p < 0.001), and 1.32 (95% CI, 1.28-1.36; p < 0.001), respectively. In addition, the prevalence of IDA increased with higher numbers of atopic diseases. In conclusion, the prevalence of IDA/AI was higher in patients with atopic disease, even after adjusting for demographic characteristics and other risk factors. Further study is needed to distinguish between IDA and AI and to enhance understanding of the etiology of anemia in patients with inflammatory conditions.

Appropriateness of Otic Quinolone Use among Privately Insured US Patients.

OBJECTIVE: Considering emerging safety concerns involving otic quinolones, we assessed the extent of otic quinolone use for questionable indications. STUDY DESIGN: Descriptive cross-sectional study of a national sample of privately insured patients. SETTING: Outpatient encounters in the United States. SUBJECTS AND METHODS: Children and adults with outpatient pharmacy-dispensing claims for new prescriptions of otic or ophthalmic quinolones in 2017 were identified within the IBM MarketScan Commercial Claims & Encounters and the Medicare Supplemental Database. Each dispensing ≥30 days apart constituted a unique episode. Only claims with supporting ear-related diagnoses on outpatient encounters ±3 days of dispensing were considered. Ophthalmic drops were excluded if eye-related diagnoses were found ±30 days. Prescribing was classified as appropriate, questionable, or undetermined. RESULTS: We found 214,897 episodes in 200,270 patients. Adults were twice as likely as children to have otic treatment with questionable indications (6.2% vs 3.0%). Sensitivity analyses with broader time windows to ascertain diagnoses showed similar proportions of questionable use. Otalgia and cerumen impaction constituted 90% of questionable indications. Family physicians (6.8%) and internists (8.0%) had higher percentages of questionable use than other specialties. CONCLUSION: Based on the demonstrated risks of quinolone ear drops, opportunities exist to decrease otic quinolone use, especially in adults.

Association between atopic disease and anemia in pediatrics: a cross-sectional study.

BACKGROUND: Atopic diseases, such as atopic dermatitis, allergic rhinitis, and asthma, are inflammatory diseases common in pediatric patients. This study investigated whether these inflammatory atopic diseases were associated with anemia in pediatrics. METHODS: A cross-sectional study was conducted using a pediatric dataset from the Health Insurance Review and Assessment Service (HIRA) of South Korea in 2016. Multivariable logistic regression, adjusting for demographic covariates was used for analyse the association between atopic disease and iron deficiency anemia (IDA). RESULTS: A total of 846,718 pediatric patients were included in the study. Of these, 19,594 (2.31%) had a diagnosis of IDA. The logistic regression analyses including covariates revealed there were association between atopic disease and IDA. The adjusted OR (aOR) of IDA was 1.42 (95% CI, 1.37-1.47) for atopic dermatitis, 1.25 (95% CI, 1.21-1.29) for allergic rhinitis, and 1.71 (95% CI, 1.65-1.76) for asthma. IDA was more prevalent in patients with multiple comorbid atopic diseases, with aOR of 1.30 (95% CI, 1.25-1.35), 1.81 (95% CI, 1.73-1.89), and 2.58 (95% CI, 2.43-2.73) for 1, 2, or 3 atopic diagnoses. There was no evidence of multicollinearity among covariates. CONCLUSIONS: Our findings suggest that atopic disease was associated with IDA. Further study is needed to clarify the distinction between IDA and/or AI to better understand the cause of anemia in patients with inflammatory diseases.

Impact of Safety Warning on Domperidone Prescribing for Geriatric Patients in South Korea: Analysis of National Insurance Claim Data.

Domperidone is a dopamine antagonist used for the symptomatic management of nausea and vomiting. Many countries banned or add a black box warning due to an increased risk of serious adverse cardiac effects. In 2014, the Korea Ministry of Food and Drug Safety also released a safety warning to carefully consider adverse cardiac effects when prescribing domperidone. Therefore, we conducted this study to analyze the impact of the safety warning on domperidone prescribing. This study included patients 65 years or older who used national health insurance services in the years 2011 and 2016, using the national patient sample dataset in South Korea. We analyzed the characteristics of domperidone prescribing and compared on pre- and post-safety warning. Prescribing frequency of domperidone was significantly reduced from 603,962 cases in 2011 to 24,623 cases in 2016. In 2011, 53,272 (8.8%) prescriptions were for greater than 30 mg/day, whereas only 200 (0.8%) prescriptions were in 2016. The number of patients with one or more comorbidities and electrocardiogram monitoring showed positive changes after the safety warning. In conclusion, after the 2014 safety letter was issued, domperidone was more safely prescribed in various aspects in elderly patients, including frequency of prescribing, maximum daily dose, and duration of continuous prescription.

Satisfaction and expressed needs of pharmaceutical care services and challenges recognized by patients in South Korea.

PURPOSE: To assess the degree of satisfaction and expressed needs of pharmaceutical care services in patients with chronic diseases and explore the factors related to the needs from patients' perspectives for the further development of pharmaceutical care service models. PATIENTS AND METHODS: A cross-sectional survey of 220 patients (mean age ± SD: 61.3±13.1, male:female: 104:116) was conducted. The questionnaire was structured to measure patients' degree of satisfaction and expressed needs using a 5-point Likert scale. Additionally, preferred duration, methods of service delivery, and willingness to pay were surveyed. Responses were analyzed using an ordinal regression method to predict factors that were related to pharmaceutical care services. RESULTS: Sixty-seven patients had experienced pharmaceutical care services. Their satisfaction levels were high in all categories; however, there were no significant differences between categories. The levels of expressed needs were similar among categories without significant differences. The preferred delivery method was a face-to-face conversation combined with being provided with written information (53.2%). The preferred duration was ≤10 min (70.5%). About 48% of the patients showed willingness to pay for the service. Education level and region influenced patients' needs. CONCLUSION: The satisfaction and needs of pharmaceutical care services was very positive; however, noticing only a third of patients experienced pharmaceutical care services, this may indicate a lack of awareness and less appreciation of pharmacists by patients. Details concerning patients' awareness and the value of pharmaceutical care services require further investigation.

Prioritization of diseases for the development of a pharmaceutical care service model in South Korea using the analytic hierarchy process
.

OBJECTIVE: Drug therapy plays a critical role in most chronic diseases. Effectiveness of pharmaceutical care services in the improvement of clinical, social, or economic outcomes has been scientifically proven through numerous studies. In South Korea, to optimize and standardize pharmaceutical care for patients with chronic metabolic diseases, the development of a pharmaceutical care service model is needed. MATERIALS: To determine the priority of diseases in developing pharmaceutical care service models, analytic hierarchny process (AHP)analysis was used. A survey questionnaire standardized with detailed evaluation areas and an index, to ensure sufficient understanding and identical standards of evaluators, was designed. It was prepared for pair-wise comparisons of individual criteria of candidate diseases. METHODS: Medical specialists and pharmacists who have clinical experience and expertise in chronic metabolic diseases or at least 10 years of experience in pharmacy practice were recruited. They responded to a survey consisting of nine sections by using the pair-wise comparison method. RESULTS: A total of seven candidate diseases were selected for prioritization. Diabetes mellitus was given the highest score of 0.2695, cardiovascular disease (0.2598) being the next, followed by chronic kidney disease (0.2000), and cerebrovascular diseases (0.1087). The criteria were weighted as follows: disease characteristics (0.4964), patient-oriented care (0.3649), and improvement in services (0.1386). CONCLUSION: Diabetes, cardiovascular diseases, and chronic kidney disease were found to have high priority in developing a pharmaceutical care service model in South Korea. In the future, further research for the development and application of pharmaceutical care services models for different types of diseases is required.
.