A Comparative Study on the Clinical Efficacy and Safety between Combination Therapy with CDK 4/6 Inhibitor and AI Versus AI Monotherapy in HR+/HER type2- Advanced Breast Cancer: Updated Meta-analysis

Objective@#The aim of the study was to perform a meta-analysis of randomized clinical trials to compare the clinical efficacy and safety between combination of cyclin-dependent kinase (CDK) 4/6 inhibitors with aromatase inhibitors (AIs) and AIs alone in patients with hormone receptor+/human epidermal growth factor receptor type2-(HR+/HER2-) advanced breast cancer. @*Methods@#Published clinical studies were identified through electronic database searches until February 2019. Literature qualities were assessed by the Scottish Intercollegiate Guidelines Network Checklist. Key endpoints of efficacy were progression-free survival (PFS), objective response rate (ORR), and clinical benefit (CB). Endpoints of safety were adverse events (AEs) (neutropenia, leukopenia, any grade 3/ 4 AEs, and serious AEs) and on-treatment death. Meta-analysis was performed using the RevMan 5.3 software. @*Results@#The selected five studies were evaluated as “good” in quality assessment. Compared to AIs alone, the combination therapy significantly improved PFS (pooled hazard ratio=0.55; 95% confidence interval (CI) 0.49-0.62), ORR (odds ratio=1.78; 95% CI=1.49-2.13), and CB (odds ratio=1.86; 95% CI=1.51-2.28). The prevalence of AEs was significantly higher in the combination group than in the AIs alone group. On-treatment death was greater in the combination group than in the AIs alone group, although insignificant. @*Conclusion@#The combination therapy of CDK4/6 inhibitors with AIs was more effective for the treatment of HR+/HER2- advanced breast cancer, but less safe than AIs alone. The combination therapy should be effectively managed through patient monitoring, and further studies are needed to reduce AEs in the combination therapy of CDK4/6 inhibitors with AIs.

A Comparative Study on the Clinical Efficacy and Safety between Combination Therapy with CDK 4/6 Inhibitor and AI Versus AI Monotherapy in HR+/HER type2- Advanced Breast Cancer: Updated Meta-analysis

Objective@#The aim of the study was to perform a meta-analysis of randomized clinical trials to compare the clinical efficacy and safety between combination of cyclin-dependent kinase (CDK) 4/6 inhibitors with aromatase inhibitors (AIs) and AIs alone in patients with hormone receptor+/human epidermal growth factor receptor type2-(HR+/HER2-) advanced breast cancer. @*Methods@#Published clinical studies were identified through electronic database searches until February 2019. Literature qualities were assessed by the Scottish Intercollegiate Guidelines Network Checklist. Key endpoints of efficacy were progression-free survival (PFS), objective response rate (ORR), and clinical benefit (CB). Endpoints of safety were adverse events (AEs) (neutropenia, leukopenia, any grade 3/ 4 AEs, and serious AEs) and on-treatment death. Meta-analysis was performed using the RevMan 5.3 software. @*Results@#The selected five studies were evaluated as “good” in quality assessment. Compared to AIs alone, the combination therapy significantly improved PFS (pooled hazard ratio=0.55; 95% confidence interval (CI) 0.49-0.62), ORR (odds ratio=1.78; 95% CI=1.49-2.13), and CB (odds ratio=1.86; 95% CI=1.51-2.28). The prevalence of AEs was significantly higher in the combination group than in the AIs alone group. On-treatment death was greater in the combination group than in the AIs alone group, although insignificant. @*Conclusion@#The combination therapy of CDK4/6 inhibitors with AIs was more effective for the treatment of HR+/HER2- advanced breast cancer, but less safe than AIs alone. The combination therapy should be effectively managed through patient monitoring, and further studies are needed to reduce AEs in the combination therapy of CDK4/6 inhibitors with AIs.

Meta-analysis on the Efficacy of Glutamate Receptor Antagonists for Acute Migraine Treatment

BACKGROUND@#Glutamate is implicated in the pathophysiology of migraine, a common neurological disorder. Therefore, glutamate receptor antagonists (GluRAs) have been suggested as a novel migraine treatment that are able to overcome the limitations of triptans.@*OBJECTIVE@#The aim of this study was to perform a meta-analysis to assess the efficacy of GluRAs for patients with migraine. Method: The PubMed, Cochrane Library, CINAHL, and Clinical Trial.gov databases were searched for randomized placebo-controlled trials of the efficacy of GluRAs for patients with migraine conducted up to August 2019. Two independent reviewers screened the literature according to inclusion and exclusion criteria and performed quality assessment and data extraction. Review Manager 5.3 software was used for the meta-analysis.@*RESULTS@#Three studies involving a total of 206 patients were included in the final analysis. Compared with placebo, GluRAs significantly improved the pain-free response at 2 hours (odds ratio [OR]=3.85, 95% confidence intervals [CIs]=1.63–9.09) and the 24-hour sustained pain freedom (OR=7.40; 95% CIs=2.36–23.20). The use of rescue medications with GluRAs was lower compared to that with placebo, but the difference was not significant (OR=0.39, 95% CI=0.10–1.47).@*CONCLUSION@#Our meta-analysis showed that GluRAs were more effective than placebo for patients with migraine.

PI3Kδ contributes to ER stress-associated asthma through ER-redox disturbances: the involvement of the RIDD–RIG-I–NF-κB axis

Hyperactivation of phosphoinositol 3-kinase (PI3K) has been suggested to be a potential mechanism for endoplasmic reticulum (ER) stress-enhanced airway hyperresponsiveness, and PI3K inhibitors have been examined as asthma therapeutics. However, the regulatory mechanism linking PI3K to ER stress and related pathological signals in asthma have not been defined. To elucidate these pathogenic pathways, we investigated the influence of a selective PI3Kδ inhibitor, IC87114, on airway inflammation in an ovalbumin/lipopolysaccharide (OVA/LPS)-induced asthma model. In OVA/LPS-induced asthmatic mice, the activity of PI3K, downstream phosphorylation of AKT and activation of nuclear factor-κB (NF-κB) were all significantly elevated; these effects were reversed by IC87114. IC87114 treatment also reduced the OVA/LPS-induced ER stress response by enhancing the intra-ER oxidative folding status through suppression of protein disulfide isomerase activity, ER-associated reactive oxygen species (ROS) accumulation and NOX4 activity. Furthermore, inositol-requiring enzyme-1α (IRE1α)-dependent degradation (RIDD) of IRE1α was reduced by IC87114, resulting in a decreased release of proinflammatory cytokines from bronchial epithelial cells. These results suggest that PI3Kδ may induce severe airway inflammation and hyperresponsiveness by activating NF-κB signaling through ER-associated ROS and RIDD–RIG-I activation. The PI3Kδ inhibitor IC87114 is a potential therapeutic agent against neutrophil-dominant asthma.

A Comparison of International Guidelines for Pediatric Asthma Pharmacotherapy

OBJECTIVE: International institutes such as Global institute for Asthma(GINA), KAAACI(Republic of Korea), NHLBI(USA), BTS(UK) and JSA(Japan) have published guidelines for asthma treatment. The aim of this study was to compare the representatives' international guidelines of pharmacotherapy for pediatric asthma. METHODS: The recommendations related to pharmacotherapy for pediatric asthma were extracted from the latest representatives' international guidelines, and comprehensive comparisons were conducted. RESULTS: Major comparison outcomes between international guidelines were evaluated as follows: classification system on severity and pediatric age group, recommendation for inhaled corticosteroid dose, recommendation for pediatric age group of theophylline in mild asthma, and recommendation for pediatric age group of tiotropium in severe asthma. Clinical trials emphasized the adverse effects of theophylline, whereas tiotropium demonstrated beneficial actions for pediatric asthma. Therefore, theophylline was recommended for older patients with persistent asthma, and tiotropium was considered to be suitable for younger patients with severe asthma according to GINA guidelines. CONCLUSION: These findings address the requirement to harmonize international guidelines of pharmacotherapy in pediatric asthma. In addition, the findings suggest that KAAACI needs to update its pharmacotherapy guidelines of theophylline, tiotropium and other medicines recently approved.

Comparative Study of First-in-Human Dose Estimation Approaches using Pharmacometrics

OBJECTIVE: First-in-human dose estimation is an essential approach for successful clinical trials for drug development. In this study, we systematically compared first-in-human dose and human pharmacokinetic parameter estimation approaches. METHODS: First-in-human dose estimation approaches divided into similar drug comparison approaches, regulatory guidance based approaches, and pharmacokinetic based approaches. Human clearance, volume of distribution and bioavailability were classified for human pharmacokinetic parameter estimation approaches. RESULTS: Similar drug comparison approaches is simple and appropriate me-too drug. Regulatory guidance based approaches is recommended from US Food and Drug Administration (FDA) and European Medicines Agency (EMA) regarding no-observed-adverse-effect level (NOAEL) or minimum anticipated biological effect level (MABEL). Pharmacokinetic based approaches are 8 approaches for human clearance estimation, 5 approaches for human volume of distribution, and 4 approaches for human bioavailability. CONCLUSION: This study introduced and compared all methods for first-in-human dose estimation. It would be useful practically to estimate first-in-human dose for drug development.

A Comparative Study of USA and Europe Guidelines of Rate and Rhythm Control Pharmacotherapy in Atrial Fibrillation

OBJECTIVE: Atrial fibrillation (AF) guidelines have been published in the USA and Europe. Recently, the USA and Europe have updated their guidelines, respectively. These new AF guidelines help in addressing key management issues in clinical situations. This study, therefore, systematically compared guidelines for rate and rhythm control pharmacotherapy of patients with AF between the USA (American College of Cardiology and American Heart Association, ACC/AHA) and Europe (European Society of Cardiology, ESC). METHODS: This study investigated and compared American guidelines (2014) and European guidelines (2010 and 2012). RESULTS: Generally, there are four meaningful differences between ACC/AHA and ESC guidelines. Important differences are treatment classification system, level of recommendation, drug list, and dosage. In addition, ACC/AHA described pharmacokinetic drug interactions for antiarrhythmic drugs. ESC emphasized ECG and atrioventricular nodal slowing as feature of antiarrhythmic drugs. CONCLUSION: This research addresses important use of anti-arrhythmic drugs and movement to accept recent recommendations in Korea. For the successful application of the guidelines, a role of pharmacists is crucial in clinical situation.

A Comparative Study the USA, Europe and Korea Guidelines of Antiplatelet Therapy for Patients with Acute Coronary Syndrome

OBJECTIVE: Patients with acute coronary syndrome (ACS) are typically managed with dual antiplatelet therapy of acetylsalicylic acid (aspirin) and P2Y12 receptor inhibitor. In this study, we discussed current and previous antiplatelet therapy guidelines and compared with guidelines of the USA (ACC/AHA), Europe (ESC) and Korea (KSC). METHOD: This study investigated from ACC/AHA Joint Guidelines (the USA), ESC Clinical Practice Guidelines (Europe) and Korea Society of Interventional Cardiology (Korea) web site, respectively. RESULTS: It is significant that difference between the current and the previous guidelines was integration of terminology from clopidogrel to P2Y12 receptor inhibitors since prasugrel and ticagrelor, new antiplatelet drugs, has been added. The other difference was all three guidelines has differences in dose of aspirin. The most notable difference was class of recommendation (COR) in P2Y12 receptor inhibitors. ACC/AHA and Korean guidelines recommend clopidogrel, prasugrel, and ticagrelor with COR IB; whereas, ESC recommend prasugrel and ticagrelor with IB which is higher than clopidogrel with IC. CONCLUSION: This research addresses important movement to revise the Korean existing guideline recommendations. New Korean antiplatelet therapy guideline should be avoiding obvious differences in ACC/AHA and ESC guidelines and harmonizing international guidelines.

Clinical Features of Marriage Immigrant Women and Their Babies in Perinatal Period: Comparison with Native Parturient Women and Neonates / 대한주산의학회잡지

PURPOSE: Nowadays, the population of foreign women who are married to Korean men is increasing. This study was undertaken to get clinical data for perinatal care of marriage immigrant women and their babies. METHODS: Retrospective analysis of medical records was conducted on marriage immigrant women and their babies who were admitted at Dongsan Medical Center, Keimyung University over a 5-year period (Jan. 2005-Dec. 2009). Additionally, birth year-, gestational age-, number (s) of fetus-, and gender-matched native parturient women and their babies were selected by random sampling with twice the number as the control group. RESULTS: Total 5,158 babies were born during the study period (male: 52.7%, female: 47.3%). The number of babies born from native mothers was 5,046 (97.8%). Babies born from immigrant women and other foreign mothers were 66 (1.3%) and 48 (0.9%), respectively. The most common nationality of immigrant women was Vietnam (n=43, 65.2%), and the others were China (n=13, 19.7%) and Philippines (n=6, 9.1%). Immigrant women (24.1+/-4.6 yr) were younger than native parturients (32.7+/-4.0 yr), and spouses were older in immigrant group (42.3+/-7.1 yr) than the control (35.1+/-4.5 yr) (P<0.001). The body weight of the immigrant women (59.2+/-10.5 kg) were lighter than the control (69.1+/-9.1 kg) around delivery (P<0.001). In maternal morbidity, the incidence of hepatitis B surface (HBs) antigenemia was higher in immigrant women (13.8%) than the control (3.8%) (P<0.05). Intrauterine growth retardation was more frequently developed in immigrant women, whereas hypertension and diabetes were more frequent in the control, but not significant. In babies born from immigrant women, birth weight (2,680+/-630 g) and head circumference (32.4+/-2.3 cm) were less than that (2,870+/-590 g and 33.2+/-2.1 cm) of native mothers' babies (P<0.05). Birth height was similar in two groups (47.3+/-3.3 cm vs. 47.8+/-3.3 cm). There were no differences between two groups in terms of presence of perinatal diseases in babies. CONCLUSIONS: Marriage immigrant women have a higher incidence of HBs antigenemia and their spouses tend to be elders. Babies born from immigrant women may show significant differences in physical measures including birth weight and head circumference in comparison with native mothers' babies. Therefore follow-up evaluation of growth and development during infancy is necessary.

Congenital Lipoid Adrenal Hyperplasia Developed in a Brother and Sister / 대한주산의학회잡지

Congenital lipoid adrenal hyperplasia (lipoid CAH) is an autosomal recessive disorder characterized by severe adrenal insufficiency. Clinical findings of patients are salt loss, hypoglycemia, pigmentation and male sex reversal. And also the baby with inadequate treatment may result in sudden death from adrenal crisis. We report the case of lipoid CAH developed in siblings with a brief review of associated literatures.