Investigation of Factors Affecting Adherence to Adjuvant Hormone Therapy in Early-Stage Breast Cancer Patients: A Comprehensive Systematic Review.

PURPOSE: Adherence and persistence to adjuvant hormone therapy (AHT) are seldom maintained among early-stage hormone receptor-positive breast cancer (BC) survivors, despite the significant clinical benefits of long-term AHT. As the factors influencing adherence to AHT remain unclear, this study aimed to comprehensively identify such factors and classify them into specific dimensions. METHODS: PubMed, Cochrane Library, Embase, PsycINFO, and CINAHL were searched for qualified articles. The search mainly focused on three components: early-stage (0-III) BC, oral AHT administration, and adherence to AHT, with keywords derived from MeSH and entry terms. The factors identified were then classified into six categories based on a modified WHO multidimensional model. RESULTS: Overall, 146 studies were included; the median sample size was 651 (range, 31-40,009), and the mean age of the population was 61.5 years (standard deviation, 8.3 years). Patient- and therapy-related factors were the most frequently investigated factors. Necessity/concern beliefs and self-efficacy among patient-related factors were consistently related to better adherence than depression. Although drug side effects and medication use cannot be modified easily, a refined prescription strategy for the initiation and switching of AHT is likely to increase adherence levels. CONCLUSION: An effective psychological program that encourages positive views and beliefs about medication and management strategies for each therapy may be necessary to improve adherence to AHT. Social support and a sense of belonging can be enhanced through community participation and social media for better adherence to AHT. Patient-centered communication and appropriate recommendations by physicians may be attributable to better adherence outcomes. Findings from systematically organized factors that influence adherence to AHT may contribute to the establishment of intervention strategies to benefit patients with early-stage BC to achieve optimal health.

Mobile Health Apps for Breast Cancer: Content Analysis and Quality Assessment.

BACKGROUND: The number of mobile health apps is rapidly increasing. This means that consumers are faced with a bewildering array of choices, and finding the benefit of such apps may be challenging. The significant international burden of breast cancer (BC) and the potential of mobile health apps to improve medical and public health practices mean that such apps will likely be important because of their functionalities in daily life. As the app market has grown exponentially, several review studies have scrutinized cancer- or BC-related apps. However, those reviews concentrated on the availability of the apps and relied on user ratings to decide on app quality. To minimize subjectivity in quality assessment, quantitative methods to assess BC-related apps are required. OBJECTIVE: The purpose of this study is to analyze the content and quality of BC-related apps to provide useful information for end users and clinicians. METHODS: Based on a stepwise systematic approach, we analyzed apps related to BC, including those related to prevention, detection, treatment, and survivor support. We used the keywords "breast cancer" in English and Korean to identify commercially available apps in the Google Play and App Store. The apps were then independently evaluated by 2 investigators to determine their eligibility for inclusion. The content and quality of the apps were analyzed using objective frameworks and the Mobile App Rating Scale (MARS), respectively. RESULTS: The initial search identified 1148 apps, 69 (6%) of which were included. Most BC-related apps provided information, and some recorded patient-generated health data, provided psychological support, and assisted with medication management. The Kendall coefficient of concordance between the raters was 0.91 (P<.001). The mean MARS score (range: 1-5) of the apps was 3.31 (SD 0.67; range: 1.94-4.53). Among the 5 individual dimensions, functionality had the highest mean score (4.37, SD 0.42) followed by aesthetics (3.74, SD 1.14). Apps that only provided information on BC prevention or management of its risk factors had lower MARS scores than those that recorded medical data or patient-generated health data. Apps that were developed >2 years ago, or by individuals, had significantly lower MARS scores compared to other apps (P<.001). CONCLUSIONS: The quality of BC-related apps was generally acceptable according to the MARS, but the gaps between the highest- and lowest-rated apps were large. In addition, apps using personalized data were of higher quality than those merely giving related information, especially after treatment in the cancer care continuum. We also found that apps that had been updated within 1 year and developed by private companies had higher MARS scores. This may imply that there are criteria for end users and clinicians to help choose the right apps for better clinical outcomes.

Development of a home health care service platform for ostomy patient management.

Purpose: The use of an ostomy for urination and defecation leads to reduced quality of life. Although many ostomy management strategies are needed, such strategies are often implemented by patients. Thus, there is a need for a home health care service platform that can be used in ostomy patient management. Methods: We developed an ostomy patient management platform by identifying the needs of patients and medical staff through the Chronic Care Ostomy Self-Management Training Program in the United States and from studies conducted in Korea. Results: The platform encompassed physical management, psychological management, maintenance of social function, spiritual stability, and home medical care. These components were implemented through monitoring, self-care guidance, and a community platform. For the monitoring function, a patient entered their health status in a mobile application (app); the medical staff at the affiliated hospital then monitored the stoma status through a web interface. Conclusion: Our platform allows medical staff to monitor ostomy patients through a web interface and help such patients to fully manage their ostomy at home using an app. We expect that the continued development of patient-oriented functions in our app will allow ostomy patients to experience quality of life improvements.

Comparison of risk of cardiovascular disease related adverse events between selective serotonin reuptake inhibitor users and serotonin norepinephrine reuptake inhibitor users in Korean adult patients with depression: retrospective cohort study.

Serotonin norepinephrine reuptake inhibitor (SNRI) has been increasingly administered, but the associated cardiovascular disease (CVD) related adverse events risk is not clearly understood. So, we conducted a cohort study to identified CVD-related adverse events risk of SNRI comparing to selective serotonin reuptake inhibitor (SSRI). We used Korea Health Insurance Review and Assessment data. During the period from April 2009 to March 2011, patients who were prescribed SSRI or SNRI for depression, who were followed up till March 2018, were the subjects. Hemorrhagic stroke, ischemic stroke, and myocardial infarction were selected as the outcomes. High-dimensional propensity scores were used to adjust the unmeasured confounders. the cox proportional hazard model was used for the statistical analysis. A total of 1,016,136 patients diagnosed with depression over the age of 20 were screened and there were 64,739 SSRI users and 3,711 SNRI users in the group of patients. The adjusted hazard ratio did not differ between the two groups, but the subgroup analysis according to comorbidities showed a high risk of hemorrhagic stroke in SNRI users with hypertension or diabetes mellitus.

Duloxetine and cardiovascular adverse events: A systematic review and meta-analysis.

Duloxetine has been increasingly administered, but the associated cardiovascular adverse event risk is not clearly understood. Therefore, we identified the association between duloxetine and cardiovascular adverse events through an analysis of heart rate and blood pressure change. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and psycINFO in June 2019. The title, abstract, and full text were checked in order to obtain articles. A meta-analysis was conducted with random effect model and quality of articles was evaluated using Cochrane Risk of Bias 2.0. The manuscript has been written according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) harm checklist. A total of 4009 studies were screened by the title and abstract. After reviewing 186 full texts, 17 studies were finally selected for the meta-analysis. Nine of the 17 studied duloxetine given for mood disorders and 8 for pain control. The duration of 14 studies was under 13 weeks. Cardiovascular adverse events (hypertension, myocardial infarction, transient ischemic attack, tachycardia atrial fibrillation, and cerebrovascular accident) were reported. The meta-analysis demonstrated that duloxetine increased heart rate by 2.22 beats/min (95% confidence intervals [CIs]: 1.53, 2.91) and diastolic blood pressure by 0.82 mmHg (95% CI: 0.17, 1.47). Our findings may be the signal for the safety of cardiovascular disease for short-term use of duloxetine. Well-designed pharmaco-epidemiological studies evaluating the causal relationship between long-term use of duloxetine and cardiovascular disease is still necessary.

Comparison of bleeding risks among non-vitamin K antagonist oral anticoagulants using the Korea adverse event reporting system database.

BACKGROUND: In order to ensure safer use of non-vitamin K antagonist oral anticoagulants (NOACs), continuously detecting unexpected adverse drug reactions (ADRs) after market approval is necessary. METHODS: We performed disproportionality analysis to evaluate association between ADRs and NOACs including apixaban, dabigatran, and rivaroxaban using data from the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System database (KIDS-KD) between 2012 and 2016. There was no significant signal other than bleeding when considering quantity, signal strength, seriousness, and causality. In order to evaluate the NOAC reports about bleeding, we selected 62 WHO-ART diagnostic codes associated with bleeding. Among the 26 codes that referred to major bleeding, 18 codes referred to gastrointestinal bleeding and 8 were referred to intracranial bleeding. We evaluated the significance of the signals using reporting odds ratios (RORs) adjusted for age and sex. RESULTS: Treatments with apixaban, dabigatran, and rivaroxaban were associated with 1989, 1668, and 2960 adverse events, respectively. Any type of bleeding with apixaban, dabigatran, rivaroxaban, and warfarin was reported in 174 (8.8%), 209 (12.5%), 523 (17.8%), and 620 (9.5%) events, respectively. For any bleeding, adjusted RORs of apixaban, dabigatran, and rivaroxaban were 0.99 [95% confidence interval (CI): 0.83-1.17], 1.47 (95% CI: 1.25-1.75), and 2.48 (95% CI: 2.16-2.84), respectively. With respect to major bleeding, the adjusted RORs of apixaban, dabigatran, and rivaroxaban were 1.08 (95% CI: 0.82-1.41), 1.46 (95% CI: 1.10-1.90), and 1.82 (95% CI: 1.43-2.32), respectively. CONCLUSION: Rivaroxaban might have stronger association with bleeding than apixaban and dabigatran.

Fluoxetine and Risk of Bleeding in Patients Aged 60 Years and Older Using the Korea Adverse Event Reporting System Database: A Case/Noncase Study.

BACKGROUND: Depression, the leading cause of nonfatal disease burden, has a strong correlation with suicide and affects approximately 7% of the general elderly population. Adverse drug reactions in older patients are particularly important because of reduced drug metabolism, polypharmacy, drug-drug interactions, and drug-disease interactions. Fluoxetine is the first representative selective serotonin reuptake inhibitor but is associated with the possibility of hemorrhage based on its mechanism of action. Serious cases of gastrointestinal bleeding and cerebral hemorrhage have been reported, raising concerns about the safety of this drug. METHODS: We detected signals of bleeding risk associated with fluoxetine in an elderly population using the Korea Adverse Event Reporting System database. Reporting odds ratios and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 16,517 adverse events related to antidepressants were reported. The reporting odds ratios for fluoxetine were 2.34 (95% CI, 1.03-5.34) for total bleeding, 4.41 (95% CI, 1.60-12.15) for major bleeding, 2.06 (95% CI, 0.28-15.03) for gastrointestinal bleeding, and 6.12 (95% CI, 2.14-22.60) for brain hemorrhage compared with those of all other antidepressants. CONCLUSIONS: We detected safety signals with total bleeding, major bleeding, and brain hemorrhage related to fluoxetine. For patients with a high risk of bleeding, such as the elderly population, prescribing antidepressants other than fluoxetine can be considered. The results of this study provide preliminary evidence of a relationship between fluoxetine and hemorrhage but have wide 95% CIs. Further pharmacoepidemiological studies will be needed to confirm the risk of bleeding associated with fluoxetine.

Impact of the Health Insurance Coverage Policy on Oral Anticoagulant Prescription among Patients with Atrial Fibrillation in Korea from 2014 to 2016.

BACKGROUND: To evaluate oral anticoagulant (OAC) utilization in patients with atrial fibrillation after the changes in the health insurance coverage policy in July 2015. METHODS: We used the Health Insurance Review and Assessment Service-National Patient Samples (HIRA-NPS) between 2014 and 2016. The HIRA-NPS, including approximately 1.4 million individuals, is a stratified random sample of 3% of the entire Korean population using 16 age groups and 2 sex groups. The HIRA-NPS comprises personal and medical information such as surgical or medical treatment provided, diagnoses, age, sex, region of medical institution, and clinician characteristics. The studied drugs included non-vitamin K antagonist OACs (NOACs) such as apixaban, dabigatran, edoxaban, and rivaroxaban, and were compared with warfarin. We analyzed drug utilization pattern under three aspects: person, time, and place. RESULTS: The number of patients with atrial fibrillation who were prescribed OACs was 3,114, 3,954, and 4,828; and the proportions of prescribed NOACs to total OACs were 5.1%, 36.2%, and 60.8% in 2014, 2015, and 2016, respectively. The growth rate of OACs prescription increased from 61.4 patients/quarter before June 2015 to 147.7 patients/quarter thereafter. These changes were predominantly in elderly individuals aged more than 70 years. The proportion of NOACs to OACs showed significant regional difference. CONCLUSION: The change of health insurance coverage policy substantially influenced OACs prescription pattern in whole Korean region. But the impact has been significantly different among regions and age groups, which provides the evidence for developing standard clinical practice guideline on OACs use.

High Level Physical Activity and Prevalence of Cardiovascular Disease Using the Korea National Health and Nutrition Examination Survey Data, 2007-2013.

OBJECTIVES: The purpose of our study was to evaluate the association between the intensity of physical activity (PA) and prevalence of cardiovascular disease (CVD) using Korean representative data. METHODS: We analyzed 39 804 participant data from the Korea National Health and Nutrition Examination Survey, 2007-2013. Exposure variable was three levels of PA (low, medium, and high) in a week, and outcome variable was prevalence of CVD based on patient self-recognition and doctor's diagnosis. Complex logistic regression analysis was performed to evaluate the relationship between level of PA and CVD adjusted by body mass index, hypertension, hypercholesterolemia, diabetes mellitus, stress recognition, household income, smoking, and current drinking. The indices of association w ere estimated as crude prevalence odds ratio (POR), adjusted POR, and their 95% confidence interval (CI). All statistical analyzes were performed using complex sample analysis procedure of the SPSS version 23.0. RESULTS: When all variables were adjusted, only high level PA in women showed a significant association with stroke (adjusted POR by patient's self-recognition, 0.57; 95% CI, 0.32 to 0.99, adjusted POR by doctor's diagnosis, 0.55; 95% CI, 0.34 to 0.87) and CVD (adjusted POR by doctor's diagnosis, 0.68; 95% CI, 0.48 to 0.96). CONCLUSIONS: High level PA in women has a significant reverse association with prevalence of stroke and CVD in Korea. Further study for elucidating the mechanism will be needed.

Data-mining for detecting signals of adverse drug reactions of fluoxetine using the Korea Adverse Event Reporting System (KAERS) database.

Selective serotonin reuptake inhibitors (SSRIs) have become one of the most broadly used medications in psychiatry. Fluoxetine is the first representative antidepressant SSRI drug approved by the Food and Drug Administration (FDA) in 1987. Safety information on fluoxetine use alone was less reported than its combined use with other drugs. There were no published papers on adverse drug reactions (ADRs) of fluoxetine analyzing spontaneous adverse events reports. We detected signals of the adverse drug reactions of fluoxetine by data mining using the Korea Adverse Events Reporting System (KAERS) database. We defined signals in this study by the reporting odds ratios (ROR), proportional reporting ratios (PRR), and information components (IC) indices. The KAERS database included 860,224 AE reports, among which 866 reports contained fluoxetine. We compared the labels of fluoxetine among the United States, UK, Germany, France, China, and Korea. Some of the signals, including emotional lability, myositis, spinal stenosis, paradoxical drug reaction, drug dependence, extrapyramidal disorder, adrenal insufficiency, and intracranial hemorrhage, were not labeled in the six countries. In conclusion, we identified new signals that were not known at the time of market approval. However, certain factors should be required for signal evaluation, such as clinical significance, preventability, and causality of the detected signals.

Association between body size, weight change and depression: systematic review and meta-analysis.

BackgroundThe association between body size, weight change and depression has not been systematically summarised, especially for individuals who are underweight.AimsTo conduct a systematic review and a meta-analysis to examine the association between indices of body size, weight change and depression.MethodA total of 183 studies were selected. Fully adjusted hazard ratios (HRs) or odds ratios (ORs) were extracted. A total of 76 studies contributed to data synthesis with a random-effect model, and subgroup analyses were conducted to evaluate the effect of potential moderators.ResultsIn cohort studies, underweight at baseline increased the risk of subsequent depression (OR = 1.16, 95% CI 1.08-1.24). Overweight (BMI 25-29.9 kg/m2) showed no statistically significant relationship with depression overall; however, the subgroup analyses found different results according to gender (men: OR = 0.84, 95% CI 0.72-0.97, women: OR = 1.16, 95% CI 1.07-1.25). In cross-sectional designs, obesity with BMI >40 kg/m2 showed a greater pooled odds ratio than obesity with BMI >30 kg/m2ConclusionsBoth underweight and obesity increase the risk of depression. The association between overweight and depression differs by gender.

Signal Detection of Imipenem Compared to Other Drugs from Korea Adverse Event Reporting System Database.

PURPOSE: To detect signals of adverse drug events after imipenem treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD). MATERIALS AND METHODS: We performed data mining using KIDS-KD, which was constructed using spontaneously reported adverse event (AE) reports between December 1988 and June 2014. We detected signals calculated the proportional reporting ratio, reporting odds ratio, and information component of imipenem. We defined a signal as any AE that satisfied all three indices. The signals were compared with drug labels of nine countries. RESULTS: There were 807582 spontaneous AEs reports in the KIDS-KD. Among those, the number of antibiotics related AEs was 192510; 3382 reports were associated with imipenem. The most common imipenem-associated AE was the drug eruption; 353 times. We calculated the signal by comparing with all other antibiotics and drugs; 58 and 53 signals satisfied the three methods. We compared the drug labelling information of nine countries, including the USA, the UK, Japan, Italy, Switzerland, Germany, France, Canada, and South Korea, and discovered that the following signals were currently not included in drug labels: hypokalemia, cardiac arrest, cardiac failure, Parkinson's syndrome, myocardial infarction, and prostate enlargement. Hypokalemia was an additional signal compared with all other antibiotics, and the other signals were not different compared with all other antibiotics and all other drugs. CONCLUSION: We detected new signals that were not listed on the drug labels of nine countries. However, further pharmacoepidemiologic research is needed to evaluate the causality of these signals.

Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database.

We conducted pharmacovigilance data mining for a ß-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability.

IFN-gamma down-regulates TGF-beta1-induced IgA expression through Stat1 and p300 signaling.

IFN-gamma has been shown to either up- or down-regulate the expression of specific TGF-beta1-induced target genes. We investigated the effect of IFN-gamma on TGF-beta1-induced IgA isotype expression. We found that IFN-gamma inhibited not only TGF-beta1-induced germ-line (GL) alpha transcription, but also IgA secretion by TGF-beta1-stimulated murine B cells. Overexpression of Stat1 diminished TGF-beta1-induced, Smad3/4-and Runx3-mediated GL alpha promoter activity. Overexpression of p300 also increased the promoter activity, while its effect was abrogated by co-transfected Stat1. Stat1 interfered with the Smad3:p300 interaction, likely due to a stronger Stat1:p300 binding affinity. These results indicate that Stat1 can inhibit GL alpha transcription through binding to p300. Further, overexpression of SOCS1, a JAK inhibitor, diminished the antagonistic effect of IFN-gamma on TGF-beta1-induced GL alpha transcription and IgA secretion. These results indicate that JAK/Stat1-mediated IFN-gamma signaling antagonizes TGF-beta1-induced GL alpha transcription, mainly through deprivation of p300 from Smad3, resulting in decreased IgA synthesis.

Tiul1 and TGIF are Involved in Downregulation of TGFbeta1-induced IgA Isotype Expression.

TGF-beta1 is well known to induce Ig germ-line alpha (GLalpha) transcription and subsequent IgA isotype class switching recombination (CSR). Homeodomain protein TG-interacting factor (TGIF) and E3-ubiquitin ligases TGIF interacting ubiquitin ligase 1 (Tiul1) are implicated in the negative regulation of TGF-beta signaling. In the present study, we investigated the roles of Tiul1 and TGIF in TGFbeta1-induced IgA CSR. We found that over-expression of Tiul1 decreased TGFbeta1-induced GLalpha promoter activity and strengthened the inhibitory effect of Smad7 on the promoter activity. Likewise, overexpression of TGIF also diminished GLalpha promoter activity and further strengthened the inhibitory effect of Tiul1, suggesting that Tiul1 and TGIF can down-regulate TGFbeta1-induced GLalpha expression. In parallel, overexpression of Tiul1 decreased the expression of endogenous IgA CSR-predicitive transcripts (GLT(alpha), PST(alpha), and CT(alpha)) and TGFbeta1-induced IgA secretion, but not GLT(gamma3) and IgG3 secretion. Here, over-expressed TGIF further strengthened the inhibitory effect of Tiul1. These results suggest that Tiul1 and TGIF act as negatively regulators in TGFbeta1-induced IgA isotype expression.