Prediction of medication-related osteonecrosis of the jaws using machine learning methods from estrogen receptor 1 polymorphisms and clinical information.

Objective: The purpose of this study was to evaluate the effect of estrogen receptor 1 (ESR1) polymorphisms on the development of medication-related osteonecrosis of the jaws (MRONJ) in women with osteoporosis. Methods: A total of 125 patients taking bisphosphonates was evaluated the relationship between MRONJ occurrence and single nucleotide polymorphisms (SNPs) of ESR1. Clinical information was collected, including current age, treatment duration, and comorbidity. Univariate and Multivariable regression analyzes were performed to evaluate the independent predictive factors for MRONJ occurrence. Predictive models were constructed using machine learning methods such as Lasso regression, Random forest (RF), and Support vector machine (SVM). The area under the receiver-operating curve (AUROC) was used to evaluate the performance of a binary classifier. Result: Two SNPs of ESR1 (rs4870056 and rs78177662) were significantly associated with MRONJ development. Patients with variant allele (A) of rs4870056 showed 2.45 times (95% CI, 1.03-5.87) the odds of MRONJ occurrence compared to those with wild-type homozygote (GG) after adjusting covariates. Additionally, carriers with variant allele (T) of rs78177662 had higher odds than those with wild-type homozygote (CC) (adjusted odds ratio (aOR), 2.64, 95% CI, 1.00-6.94). Among demographic variables, age ≥ 72 years (aOR, 3.98, 95% CI, 1.60-9.87) and bisphosphonate exposure ≥48 months (aOR, 3.16, 95% CI, 1.26-7.93) were also significant risk factors for MRONJ occurrence. AUROC values of machine learning methods ranged between 0.756-0.806 in the study. Conclusion: Our study showed that the MRONJ occurrence was associated with ESR1 polymorphisms in osteoporotic women.

Nutrition Therapy by Nutrition Support Team: A Comparison of Multi-Chamber Bag and Customized Parenteral Nutrition in Hospitalized Patients.

This study aimed to investigate the activity of a nutrition support team (NST) and the trends of multi-chamber bag (MCB) and customized parenteral nutrition (PN) with NST consultations in South Korea. Data were obtained from the National Inpatient Sample Cohort between 2015 and 2020. Three datasets were constructed for NST consultation, MCB-PN product prescriptions, and aseptic preparation of total PN. The intersections of the NST consultation and each PN dataset were compiled into MCB-PN with NST or customized PN with a NST sub-dataset, respectively. Using personal identifiers, the patients' characteristics were evaluated in the NST cohort. A total of 91,384 reimbursements and 70,665 patients were included. The NST activity had increased by more than 50% over 6 years. Approximately 70% and 11%, respectively, of the NST cohort were classified into two subgroups: MCB-PN with NST (M-NST) and customized PN with NST (C-NST). M-NST had many elderly patients with cancer and showed a higher in-hospital mortality than C-NST (12.6% vs. 9.5%). C-NST included a larger number of patients under the age of 5 years, and the hospitalization period was more extended than M-NST (26.2 vs. 21.2 days). The present study showed that NST activities and the proportion of PN with NST consultation are gradually increasing in South Korea.

Comparative associations between anticholinergic burden and emergency department visits for anticholinergic adverse events in older Korean adults: a nested case-control study using national claims data for validation of a novel country-specific scale.

BACKGROUND: Considering the limited generalizability of previous anticholinergic burden scales, the Korean Anticholinergic Burden Scale (KABS) as a scale specific to the Korean population was developed. We aimed to validate the KABS by detecting the associations between high anticholinergic burden, measured with the KABS, and emergency department (ED) visits compared to the pre-existing validated scales in older Korean adults. METHODS: A nested case-control study was conducted using national claims data. The cases included the first anticholinergic ED visits between July 1 and December 31, 2016. Anticholinergic ED visits were defined as ED visits with a primary diagnosis of constipation, delirium, dizziness, fall, fracture, or urinary retention. Propensity score-matched controls were identified. Average daily AB scores during 30 days before the index date were measured. Multivariate logistic regression analyses were performed. RESULTS: In total, 461,034 were included. The highest proportion of those with high AB was identified with KABS (5.0%). Compared with those who had a KABS score of 0, older adults with a score ≥ 3 were at higher risk for overall anticholinergic ED visits (aOR, 1.62, 95% CI, 1.53-1.72), as well as visits for falls/fractures (aOR: 1.54, 95% CI: 1.40-1.69), dizziness (aOR: 1.44, 95% CI: 1.30-1.59), delirium (aOR: 2.96, 95% CI: 2.28-3.83), constipation (aOR: 1.84, 95% CI: 1.68-2.02), and urinary retention (aOR: 2.13, 95% CI: 1.79-2.55). High AB by KABS showed a stronger association with overall anticholinergic ED visits and visits due to delirium and urinary retention than those by other scales. CONCLUSIONS: In conclusion, KABS is superior to pre-existing scales in identifying patients with high AB and predicting high AB-related ED visits in older Korean adults.

Prevalence of anticholinergic burden and risk factors amongst the older population: analysis of insurance claims data of Korean patients.

Background Despite growing interest in the negative clinical outcomes of multiple anticholinergic use, limited studies have evaluated anticholinergic burden in the geriatric population nationally. Objective To evaluate the prevalence of high anticholinergic burden using the newly developed Korean Anticholinergic Burden Scale in comparison with previous tools and to identify associated factors. Setting National insurance data from a cross section (20%) of older Koreans (2016). Methods Anticholinergic burden was measured using the Korean scale in comparison to the Anticholinergic Drug Scale, Anticholinergic Cognitive Burden, and Anticholinergic Risk Scale. High anticholinergic burden was defined as a summed score of ≥ 3 for concurrent medications or a dose-standardized average daily score of ≥ 3, using each anticholinergic scale. Main outcomes measured Prevalence and predictors of high anticholinergic burden. Results Data of 1,292,323 patients were analyzed. According to the Korean scale, the prevalence of high anticholinergic burden was 25.5%. This result was similar to that from the Anticholinergic Drug Scale (24.9%) and Anticholinergic Cognitive Burden (22.2%). Factors associated with an increased likelihood of anticholinergic burden include: age, gender (female), high Charlson comorbidity index score, polypharmacy, medical aid beneficiary, co-morbidities (such as schizophrenia, depression, urinary incontinence, and Parkinson's disease), frequent healthcare visits, various healthcare facilities utilized, and predominantly visiting hospital-level facilities. According to the Korean Anticholinergic Burden Scale, the major drugs contributing to the anticholinergic burden were ranitidine, chlorpheniramine, tramadol, and dimenhydrinate. Conclusion This study showed that 1 in 4 older Koreans are exposed to high anticholinergic burden. The predictors identified in this research might assist pharmacists in early interventions for their patients.

Health Behaviors Associated with Aggression in Korean Adolescents: Data from 2 Cross-sectional Studies.

Objectives: In this study, we identified the health-related behaviors associated with aggression and examined the trends in both aggression and health-related behaviors among adolescents in the Republic of Korea. Methods: We used 2 cross-sectional samples of adolescents collected from the same geographic region 10 years apart. We measured aggression using the Aggression Questionnaire. Subject characteristics of the questionnaire included age, sex, caffeine intake, alcohol consumption, smoking, regular exercise, use of medications, and unstable mood. Results: Data pertaining to 1316 and 894 students were extracted from 2006 and 2016 surveys, respectively. Based on the multivariate results, sex and smoking were associated with physical aggression in both surveys, whereas sex and unstable mood were linked to verbal aggression. Alcohol consumption, unstable mood, and use of pain medications were related to anger; indigestion and unstable mood were associated with hostility in both years. The total aggression score was significantly related to alcohol consumption and unstable mood in both years after adjusting for other confounders. Conclusions: Health-related behaviors such as alcohol consumption and unstable mood showed meaningful relations with aggression. Accordingly, we should increase public awareness of factors associated with aggression, and government agencies and schools should implement comprehensive prevention efforts.

Association between preoperative use of antithrombotic medications and intraoperative transfusion in older patients undergoing cancer surgery.

BACKGROUND: Management of antiplatelet agents and other chronic anticoagulation medications in patients scheduled for surgery can reduce intraoperative bleeding complications. However, few studies on the association of antithrombotics, relative to their duration of action, with intraoperative transfusion have been conducted. We aimed to determine the association of recent use of antithrombotics, relative to their duration of action, with intraoperative transfusion in elderly people undergoing cancer surgery. METHODS: The study subjects were patients aged 65 years or older who were scheduled for cancer surgery and presented for comprehensive geriatric assessment. We reviewed the baseline patient characteristics obtained from electronic medical records and the patients' preoperative medication history, including anticoagulants, antiplatelet agents, and streptokinase/streptodornase. RESULTS: A total of 475 cancer patients were included. Multivariate analysis showed that long-acting anticoagulant therapy before surgery was a significant risk factor for intraoperative transfusion. Long-acting anticoagulants increased the risk of transfusion approximately 15.9-fold (95% CI 1.9-136.2). The attributable risk of long-acting anticoagulants to transfusion was approximately 93.7%. Also, low body mass index (BMI) and hepato-pancreato-biliary (HPB) surgery were significantly associated with intraoperative transfusion. The adjusted odds ratios for low BMI (<18.5 kg/m2) and HPB surgery (reference: lower gastrointestinal surgery) were 5.3 (95% CI 1.8-15.4) and 4.9 (95% CI 1.9-12.5), respectively. CONCLUSIONS: It was found that the perioperative use of long-acting anticoagulants was associated with an increased risk of intraoperative transfusion, further highlighting the importance of medication optimization for elderly patients with cancer surgery.

Association of pre-operative medication use with unplanned 30-day hospital readmission after surgery in oncology patients receiving comprehensive geriatric assessment.

BACKGROUND: This study aimed to determine whether pre-operative medication use is associated with unplanned 30-day readmission in elderly people undergoing cancer surgery. METHODS: Patients aged 65 years or older who were scheduled for cancer surgery and presented for comprehensive geriatric assessment were included. Comparisons of variables between patients with readmission and those without readmission were performed by univariate and multivariate analyses. RESULTS: A total of 473 patients were included. Multivariate analysis showed that pre-operative discontinuation-requiring medications (PDRMs) and gastrointestinal/hepato-pancreato-biliary (GI/HPB) cancer were significant factors for 30-day readmission. PDRM increased the risk of readmission by about 2.2-fold. Attributable risk of PDRM to readmission was around 55%. The adjusted odds ratio and attributable risk for GI/HPB surgery was 3.4 (95% CI 1.0-11.5) and 70.8%, respectively. CONCLUSIONS: Medication use has an impact on unplanned 30-day readmission in geriatric oncology patients, further highlighting the importance of medication optimization for elderly patients with cancer surgery.

Effects of Polymorphisms in Myc-Related Genes on Bleeding Complications in Patients with Stable Warfarin Responses.

OBJECTIVES: This study aimed to identify the possible effects of Myc and 8q24 polymorphisms on bleeding complications in patients who maintained international normalized ratio (INR) of 2.0-3.0 with warfarin therapy after cardiac valve replacement. METHODS: Twenty-five single nucleotide polymorphisms were analyzed, including VKORC1, CYP2C9, Myc, and 8q24. Univariate and multivariate analyses were conducted to evaluate the associations between genetic polymorphisms and bleeding complications. Attributable risk and the number needed to genotype (NNG) were also calculated to evaluate the potential clinical value of genotyping. RESULTS: We included 142 patients, among whom 21 experienced bleeding complications. Multivariate models showed that patients carrying the CC genotype of rs6983561 and the A allele of rs13281615 at 8q24 had 27.6- and 10.0-fold higher bleeding complications, compared with patients with the A allele and the GG genotype, respectively. For rs6983561, the attributable risk and NNG were 96.4% and 36.8, respectively, whereas, for rs13281615, the attributable risk and NNG were 90.0% and 8.3, respectively. Atrial fibrillation was associated with a 5.5-fold increased risk of bleeding complications. The AUROC value was 0.761 (95% CI 0.659-0.863, p<0.001), and the Hosmer-Lemeshow test showed that the fitness of the multivariate analysis model was satisfactory (χ 2=0.846; 3 degrees of freedom; p=0.838). CONCLUSIONS: Bleeding complications during warfarin therapy were associated with 8q24 polymorphisms and atrial fibrillation in patients with mechanical heart valves.

Comparisons of doxycycline solution with talc slurry for chemical pleurodesis and risk factors for recurrence in South Korean patients with spontaneous pneumothorax.

PURPOSE: Talc slurry (TS) has been commonly used with high success rates in managing spontaneous pneumothroax (SP), but there were concerns of post-procedural complications. Alternatively, doxycycline solution (DS) was used successfully. This retrospective study aims to compare the effectiveness and safety between talc and doxycycline as a sclerosing agent and to investigate risk factors for recurrence in patients with SP. METHODS: The review of medical records between January 2011 and December 2014 was conducted on 83 patients with SP who underwent pleurodesis with either TS (n=16) or DS (n=67). Recurrence and complications were compared between the DS and TS groups. Associations between recurrence after DS treatment and various factors were analysed. RESULTS: Recurrence was significantly higher in the DS group than in the TS group (P=0.033), whereas complications were higher in the TS group than the DS group: fever was significantly higher in the TS group (P=0.001). Recurrences associated with doxycycline use were found significantly more often in patients with recurrent diagnosis of SP, height/weight ≥3.25 cm/kg and weight <55 kg. CONCLUSION: Talc was more effective without recurrence compared with doxycycline. Clinically insignificant fever associated with pleurodesis was more common with talc. Low weight, high height to weight ratio and recurrent diagnosis of SP were associated with higher recurrence after doxycycline treatment.

Association between VEGFA gene polymorphisms and bleeding complications in patients maintaining therapeutic international normalized ratio.

Aim: This study was designed to identify the possible effects of VEGFA polymorphisms on the occurrence of bleeding complications in patients with mechanical heart valves who have achieved therapeutic international normalized ratio (INR). Materials & methods: 13 SNPs of VEGFA were analyzed. Uni- and multi-variate analyses were conducted to identify associations between polymorphisms and bleeding complications. Results & conclusion: Patients with the CC genotype of rs35410204 had an approximately tenfold higher bleeding complication than those with the T allele. For rs866236, patients who had wild-type homozygotes showed an approximately 2.9-fold higher bleeding complication than C allele carriers. This study demonstrated that bleeding complications during warfarin therapy are associated with VEGFA polymorphisms in patients with mechanical heart valves.

Association of pre-operative medication use with post-surgery mortality and morbidity in oncology patients receiving comprehensive geriatric assessment.

BACKGROUND: Comprehensive geriatric assessment (CGA) has become a predictor for elderly cancer patients in post-surgical complications, including post-discharge institutionalization and mortality. AIMS: To determine whether pre-operative medication use is associated with post-operative morbidity and mortality in oncology patients receiving CGA. METHODS: Patients aged 65 years or older who were scheduled for cancer surgery and presented for CGA were included in the present study. Baseline characteristics of patients were collected from electrical medical records, and pre-operative medication review was performed. The primary outcome was death within 30 days after surgery and post-discharge institutionalization. RESULTS: A total of 475 cancer patients were included. Among them, three patients died within 30 days after surgery and 14 patients were discharged to another institution. All patients who died within 30 days after surgery had polypharmacy with marginal significance (P = 0.087). Multivariate analysis models were constructed using significant factors for post-surgery institutionalization from univariate analysis: Model I (polypharmacy and transfusion), Model II (polypharmacy and infection), and Model III (polypharmacy, transfusion, and infection). Infection was the most significant factor. Its adjusted odds ratio was as large as 11.1 and attributable risk was almost 91%. In pre-surgery medication use, only polypharmacy showed significant association with post-discharge institutionalization. Attributable risk of polypharmacy was around 75%. CONCLUSIONS: It is possible that pre-operative medication use has impact on death and post-discharge institutionalization in geriatric oncology patients, further highlighting the importance of medication optimization for elderly patients with cancer surgery.

Preoperative medication use and its association with postoperative length of hospital stay in surgical oncology patients receiving comprehensive geriatric assessment.

AIM: The present study aimed to investigate whether preoperative medication use is associated with postoperative length of hospital stay in older adults undergoing cancer surgery. METHODS: Patients aged ≥65 years who were scheduled for cancer surgery and presented for preoperative comprehensive geriatric assessment were included in the present study. Cognitive function evaluation and preoperative medication review were carried out, as well as baseline characteristics of participants collected from electronic medical records. The primary efficacy variable was the postoperative length of stay (LOS) in hospital. RESULTS: A total of 475 cancer patients were included for the analysis. Baseline characteristics of participants including older age, lower body mass index (BMI) and male sex were associated with longer postoperative stay. Among the clinical variables, cancer type, number of medications, potentially inappropriate medication (PIM) and delirium-inducing medication were found as statistically significant factors for postoperative LOS. In multivariate analysis, variables independently associated with postoperative LOS were cancer type, PIM use, BMI, and the number of medications after controlling for age, BMI, sex, cancer type, the number of medications, PIM, and delirium-inducing medication. In subgroup analysis of gastrointestinal cancer, multiple linear regression analysis showed that PIM use and BMI were significantly associated with LOS after adjustment for age, sex, and number of medication. CONCLUSIONS: The present study supports the impact of medication use on postoperative LOS in geriatric oncology patients. The results add a further aspect to medication optimization in older patients undergoing cancer surgery. Geriatr Gerontol Int 2018; 18: 12-19.

Association between CACNA1C gene polymorphisms and ritodrine-induced adverse events in preterm labor patients.

PURPOSE: As a tocolytic agent, ritodrine has been used in European and Asian countries but has lost popularity due to safety concerns. This study aimed to investigate the relationship between adverse drug events caused by ritodrine and the CACNA1C polymorphisms in preterm labor patients. METHODS: Data were collected from medical records including maternal age, gestational age, body mass index, dilation score, effacement score, modified Bishop score, maximum infusion rate, and adverse drug events. Five single-nucleotide polymorphisms of the CACNA1C gene (rs10774053, rs215994, rs215976, rs2239128, and rs2041135) were analyzed. RESULTS: One hundred eighty-six patients were included, 33 of whom had adverse drug events. A allele carriers of rs10774053 showed about 0.293-fold lower adverse drug events than GG genotype carriers (p = 0.012, absolute risk reduction = 16.5%) after adjusting for other confounding variables; the number needed to genotype for preventing one patient with GG genotype from suffering higher incidence of adverse drug events was calculated to be 14.6. Increase in maximum infusion rate of 1 mL/h was associated with a 1.03-fold (95% CI 1.01~1.06, p = 0.005) increased risk of adverse drug events. None of the patients with a CC genotype of rs215994 had adverse drug events, whereas 22.1% of the T allele carriers had adverse drug events. CONCLUSION: This study showed that CACNA1C gene polymorphisms could alter the probability of adverse drug event risk when ritodrine is used in preterm labor.

Association of pre-operative medication use with post-operative delirium in surgical oncology patients receiving comprehensive geriatric assessment.

BACKGROUND: Older patients undergoing surgery tend to have a higher frequency of delirium. Delirium is strongly associated with poor surgical outcomes. This study evaluated the association between pre-operative medication use and post-operative delirium (POD) in surgical oncology patients receiving comprehensive geriatric assessment (CGA). METHODS: A total of 475 patients who were scheduled for cancer surgery and received CGA from January 2014 to June 2015 were included. Pre-operative medication review through CGA was conducted on polypharmacy (≥5 medications), delirium-inducing medications (DIMs), fall-inducing medications (FIMs), and potentially inappropriate medications (PIMs). POD was confirmed by psychiatric consultation, and DSM-V criteria were used for diagnosing delirium. The model fit of the prediction model was assessed by computing the Hosmer-Lemeshow goodness-of-fit test. Effect size was measured using the Nagelkerke R(2). Discrimination of the model was assessed by an analysis of the area under receiver operating curve (AUROC). RESULTS: Two models were constructed for multivariate analysis based on univariate analysis; model I included dementia and DIM in addition to age and sex, and model II included PIM instead of DIM of model I. Every one year increase of age increased the risk of POD by about 1.1-fold. DIM was a significant factor for POD after adjusting for confounders (AOR 12.78, 95 % CI 2.83-57.74). PIM was also a significant factor for POD (AOR 5.53, 95 % CI 2.03-15.05). The Hosmer-Lemeshow test results revealed good fits for both models (χ(2) = 3.842, p = 0.871 for model I and χ(2) = 8.130, p = 0.421 for model II). The Nagelkerke R(2) effect size and AUROC for model I was 0.215 and 0.833, respectively. Model II had the Nagelkerke R(2)effect size of 0.174 and AUROC of 0.819. CONCLUSIONS: These results suggest that pharmacists' comprehensive review for pre-operative medication use is critical for the post-operative outcomes like delirium in older patients.

Association of inflammatory gene polymorphisms with mechanical heart valve reoperation.

BACKGROUND: Various complications lead to reoperation in patients who undergo prosthetic valve replacement where inflammatory process could be involved. The goals of this study were to identify risk factors that correlate with reoperation in patients with prosthetic heart valves and to investigate the relationship between reoperation and inflammatory gene polymorphisms. RESULTS: The study included 228 patients from the EwhA-Severance Treatment Group of Warfarin. Single nucleotide polymorphisms of c-reactive protein (CRP), interferon-gamma, interleukin 1 beta, interleukin 6, interleukin 10, transforming growth factor beta 1, and tumor necrosis factor genes were genotyped by means of SNaPshot and TaqMan assays. Thirty-nine patients (17.1 %) underwent more than one heart valve operation. A threefold increased risk for heart valve reoperation was evident in homozygous variant-type (TT) carriers as compared with ancestral allele carriers of CRP rs1205. Logistic regression analysis revealed that CRP rs1205 (OR 2.68, 95 % CI 1.22-5.90, p = 0.014), valve position (mitral valve OR 2.80, 95 % CI 1.01-7.80, p = 0.048; tricuspid valve OR 9.24, 95 % CI 2.46-34.70, p = 0.001; reference: aortic valve) and time after first operation (OR 1.13, 95 % CI 1.06-1.20, p < 0.001) affected the risk of reoperation. CONCLUSIONS: Inflammatory gene polymorphisms could be a possible marker of risk for reoperation in patients with prosthetic heart valve surgery.