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BACKGROUND: Hospitalization of nursing home (NH) residents impose a significant healthcare burden. However, there is still a lack of information regarding the risk of hospitalization from inappropriate prescribing in NH residents. We aimed to estimate the nationwide prevalence of potentially inappropriate medication (PIM) use among NH residents using the Korean tool and 2019 Beers criteria and to assess their associations with hospitalization or emergency department (ED) visits. METHODS: We included older adults aged 65 years or above who were admitted to NHs between July 2008 and December 2018 using national senior cohort database. The prevalence of PIM use based on the Korean medication review tool and Beers criteria on the date of admission to NH was estimated. And the adjusted hazard ratios (aHRs) of polypharmacy, numbers of PIM, each PIM category for hospitalization/ED visits within 30 days of admission to NH was calculated using Cox proportional hazard model to show the association. RESULTS: Among 20,306 NH residents, the average number of medications per person was 7.5 ± 4.7. A total of 89.3% and 67.9% of the NH residents had at least one PIM based on the Korean tool and 2019 Beers criteria, respectively. The risk of ED visits or hospitalization significantly increased with the number of PIMs based on the Korean tool (1-3: aHR = 1.24, CI 1.03-1.49; ≥4: aHR = 1.46, CI 1.20-1.79). Having four or more PIMs based on the Beers criteria increased the risk significantly (aHR = 1.30, CI 1.06-1.53) while using 1-3 PIMs was not significantly associated (aHR = 1.07, CI 0.97-1.19). Residents with any potential medication omission according to the Korean criteria, were at 23% higher risk of hospitalization or ED visits (aHR = 1.23, CI 1.07-1.40). CONCLUSIONS: This study demonstrated that PIMs, based on the Korean tool and Beers criteria, were prevalent among older adults living in NHs and the use of PIMs were associated with hospitalization or ED visits. The number of PIMs based on the Korean tool showed dose-response increase in the risk of hospitalization or ED visits.
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Casas de Saúde , Lista de Medicamentos Potencialmente Inapropriados , Humanos , Idoso , Prescrição Inadequada , Hospitalização , Instituições de Cuidados Especializados de Enfermagem , Polimedicação , Estudos RetrospectivosRESUMO
BACKGROUND: An effective test mechanism to evaluate clinical knowledge and skills of the entry-level healthcare professionals is important for providing clinical competency and improving patient care. This study aimed to develop novel, innovative computer-based test (Inno-CBT) item types for application in the national examination of Korean healthcare professionals. METHODS: This exploratory study was conducted from May 2021 to March 2022 by a team of faculty members from pharmacy schools in South Korea. A literature search using PubMed, Google Scholar, RISS, Web of Science, and KoreaMed was performed. Forum presentations, media articles, and previous reports by the Korea Health Personnel Licensing Examination Institute (KHPLEI) were included. Workshops were held, information and ideas were collected and conceptualized, and item types were designed, drafted, and refined. By repeating this process, the Inno-CBT item types were finalized. RESULTS: Forty-one Inno-CBT item types with 28 subtypes were developed. New digital technologies, such as a reactive responsive media interface, an animation insertion, multimedia embedding, and network surfing, were utilized in these novel types. It was anticipated that these Inno-CBT item types would effectively measure abilities in healthcare knowledge, problem-solving skills, and professional behaviors. Some potential barriers to implementing the Inno-CBT item types include item difficulty, operational unfamiliarity, complexity in scoring protocols, and network security. CONCLUSIONS: A variety of styles of novel Inno-CBT item types were developed to evaluate the multifaceted and in-depth professional abilities required for healthcare professionals. Prior to implementing these item types in the national examination, item validation and technical support should be conducted.
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Pessoal de Saúde , Licenciamento , Humanos , República da Coreia , Docentes , ComputadoresRESUMO
Purpose: Tacrolimus (Tac) is a widely used immunosuppressive agent in kidney transplantation. Cytochrome P450 (CYP), especially CYP3A4 enzymes are responsible for the metabolism of drugs. However, the correlation between plasma Tac concentration and CYP3A4*22 gene variants is controversial. This meta-analysis aims to evaluate the association between CYP3A4*22 polymorphism and the dose-adjusted trough concentration (C0/D) of Tac in adult kidney transplant patients. Methods: We conducted a literature review for qualifying studies using the PubMed, Web of Science, and Embase databases until July 2023. For the continuous variables (C0/D and daily dose), mean difference (MD) and corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between the CYP3A4 * 22 and Tac pharmacokinetics. We performed an additional analysis on the relationship of CYP3A5*3 with Tac PKs and analyzed the effects of CYP3A4*22 in CYP3A5 non-expressers. Results: Overall, eight eligible studies with 2,683 renal transplant recipients were included in this meta-analysis. The CYP3A4*22 allele was significantly associated with a higher C0/D (MD 0.57 ng/mL/mg (95% CI: 0.28 to 0.86; p = 0.0001) and lower mean daily dose requirement (MD -2.02 mg/day, 95% CI: -2.55 to -1.50; p < 0.00001). An additional meta-analysis demonstrated that carrying the CYP3A5*3 polymorphism greatly impacted Tac blood concentration. From the result with CYP3A5 non-expressers, CYP3A4*22 showed significant effects on the Tac C0/D and dose requirement even after adjusting the effect of CYP3A5*3. Conclusion: Patients with CYP3A4*22 allele showed significantly higher plasma C0/D of Tac and required lower daily dose to achieve the therapeutic trough level after kidney transplantation. These findings of our meta-analysis may provide further evidence for the effects of genetic polymorphism in CYP3A4 on the PKs of Tac, which will improve individualized treatment in a clinical setting.
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Safety and efficacy are essential in the process of disease treatment. However, off-label medication use is inevitable because various medications do not contain regulatory labels for pediatric use. We aimed to examine off-label medication use and analyze the risk factors correlated with adverse drug reactions (ADRs). This study was performed retrospectively using electronic medical data from a pediatric intensive care unit (PICU) of a tertiary hospital in Korea from July 2019 to June 2020. A total 6,183 prescribed medications from 502 PICU patients were examined in the present study. A total of 80% were infants or children, and 96.0% of them were treated with off-label medications. It was discovered that 4,778 off-label cases (77.2%) of the top 100 drugs had prescriptions with dosage (67.8%). Drugs prescribed to patients admitted to the cardiothoracic department (odds ratio [OR], 3.248; p = 0.019), total number of medications (OR, 1.116; p = 0.001), and length of PICU stay of ≥ 7 days (OR, 4.981; p = 0.008) were significantly associated with ADRs. ADRs were noted to be more severe in off-label use (p = 0.0426). For appropriate medication use, evidence regarding the safety of off-label medications is required and ultimately reflected in the official regulation.
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Pharmacogenomics, which is defined as the study of changes in the properties of DNA and RNA associated with drug response, enables the prediction of the efficacy and adverse effects of drugs based on patients' specific genetic mutations. For the safe and effective use of drugs, it is important that pharmacogenomic information is easily accessible to clinical experts and patients. Therefore, we examined the pharmacogenomic information provided on drug labels in Korea, Europe, Japan, and the United States (US). The selection of drugs that include pharmacogenomic information was based on the drug list that includes genetic information from the Korea Ministry of Food and Drug Safety (MFDS) and US Food and Drug Administration (FDA) websites. Drug labels were retrieved from the sites of MFDS, FDA, European Medicines Agency, and Japanese Pharmaceuticals and Medical Devices Agency. Drugs were classified as per the Anatomical Therapeutic Chemical code, and the biomarkers, labeling sections, and necessity of genetic tests were determined. In total, 348 drugs were selected from 380 drugs with available pharmacogenomic information in Korea and the US after applying the inclusion and exclusion criteria. Of these drugs, 137, 324, 169, and 126 were with pharmacogenomics information in Korea, the US, Europe, and Japan, respectively. The most commonly represented drug class was antineoplastic and immunomodulating agents. Regarding the classification as per the mentioned biomarkers, the cytochrome P450 enzyme was the most frequently mentioned information, and the targeted anticancer drugs most commonly required genetic biomarker testing. The reasons for differences in drug labeling information based on country include differences in mutant alleles according to ethnicity, frequencies at which drug lists are updated, and pharmacogenomics-related guidelines. Clinical experts must continuously strive to identify and report mutations that can explain drug efficacy or side effects for safe drug use.
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Executive functioning (EF) is a cognitive process used to perform various daily activities throughout one's lifespan. Autistic adults without intellectual disabilities (ID) also experience difficulties with EF, which is closely associated with adaptive behaviors. For this reason, it is important to improve adaptive behaviors through enhanced use of EF for autistic adults to transition into adulthood successfully. This study aims to conduct a randomized controlled trial to evaluate the effectiveness of a newly developed and modified intervention program. Thirty autistic adults without ID were randomly assigned to the treatment or waitlist group. The participants and caregivers completed various assessments and self-report questionnaires to measure everyday EF and adaptive behaviors. We performed linear mixed-effect modeling to compare the two groups. Data collected at pre-, middle, post-, and follow-up based on participants who completed the program were used to explore changes across time. While there were significant differences in the EF utility-scale (F=5.46, p = .027) between the treatment and waitlist groups, no group x time interactions were detected in other measures. Everyday EF and adaptive behaviors improved when comparing measurements at different time points (p < .001). Our program is Korea's first evidence-based intervention to improve everyday EF and adaptive behaviors for autistic adults without ID.
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Transtorno Autístico , Deficiência Intelectual , Humanos , Adulto , Função Executiva , Transtorno Autístico/terapia , Inquéritos e Questionários , Adaptação PsicológicaRESUMO
INTRODUCTION: We aimed to estimate the nationwide prevalence of potentially inappropriate medication (PIM) use in patients with terminal cancer according to two deprescribing criteria for patients with a limited lifespan. MATERIALS AND METHODS: This cross-sectional study evaluated the prevalence of PIM use using two datasets: national claims data and single-tertiary hospital data. In the claims data, patients with terminal cancer were defined as patients with cancers who died between April and June 2018 and were prescribed opioid analgesics or megestrol or were hospitalized for >90 days before the date of death. Using hospital data, patients who were enrolled in hospice care in 2019 were identified. PIM was defined according to the adjusted criteria from the Screening Tool for Older Persons' Prescriptions in frail adults with limited life expectancy (STOPPFrail) versions 1 and 2 and oncological palliative care deprescribing guidelines (OncPal) guidelines. RESULTS: From the national claims data and single-tertiary hospital data, 1,558 patients and 1,243 patients were included in the analysis, respectively. In both datasets, over 60% of patients used five or more medications (claims data: 67.7%; hospital data: 63.9%), and approximately half of them used at least one PIM (claims data: 51.5%; hospital data: 43.2%). Lipid-lowering agents, acid suppressors, and hypoglycemics were common PIMs. Polypharmacy, age, and comorbid conditions, including diabetes, were associated with PIM use. DISCUSSION: Approximately two-thirds and half of the patients with terminal cancer were exposed to polypharmacy and at least one PIM based on the STOPPFrail and OncPal criteria, respectively; therefore, deprescribing PIM in patients with terminal cancer is an urgent issue.
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Desprescrições , Neoplasias , Humanos , Idoso , Idoso de 80 Anos ou mais , Lista de Medicamentos Potencialmente Inapropriados , Prescrição Inadequada/prevenção & controle , Estudos Transversais , Neoplasias/tratamento farmacológico , Centros de Atenção TerciáriaRESUMO
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.
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Introduction: This study aimed to investigate the association between polymorphisms in fibrinogen genes and bleeding risk in patients receiving direct oral anticoagulants (DOACs). Method: Patients treated with DOACs from June 2018 to December 2021 were enrolled in the study. Genotyping was done for rs2070011, rs6050, and rs2070022 in fibrinogen alpha chain (FGA); rs1800788, rs4220, and rs4463047 in fibrinogen beta chain (FGB); and rs2066865 and rs1800792 in fibrinogen gamma chain (FGG), along with F2 rs5896 and F10 rs5960. Multivariable logistic regression analysis was performed to investigate the risk factors for bleeding and to develop a risk scoring system. Results: A total of 468 patients were included in the analysis, 14 of whom experienced major bleeding and 36 experienced clinically relevant non-major bleeding. In the multivariable analysis, overdose, anaemia, F2 rs5896, and FGG rs1800792 were found to be significantly associated with bleeding risk. Specifically, patients with the TT genotype of F2 rs5896 and the CC genotype of FGG rs1800792 had 2.1 times (95% confidence interval [CI] 1.1-3.9) and 2.7 times (95% CI 1.2-5.9) higher bleeding risk than the C allele and T allele carriers, respectively. Based on the risk scoring system, patients with 0, 1, 2, 3, 4, and 5 points were predicted to have 5.2%, 10.8%, 22.4%, 32.3%, 42.3%, and 61.8% of bleeding risk, respectively. Conclusion: To our knowledge, this is the first study to investigate the effects of polymorphisms in fibrinogen genes on DOAC response. After validation, these results will be useful for personalised DOAC therapy.
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Fibrinogênio , Hemorragia , Humanos , Fibrinogênio/genética , Feminino , Masculino , Hemorragia/induzido quimicamente , Hemorragia/genética , Idoso , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Administração Oral , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , Genótipo , Idoso de 80 Anos ou mais , Inibidores do Fator Xa/efeitos adversos , Anemia/genéticaRESUMO
Reports on the association between the solute carrier organic anion transporter 1B1 (SLCO1B1) T521C polymorphism and methotrexate-induced hepatotoxicity in patients with malignancies are inconsistent. This meta-analysis evaluated the association between the SLCO1B1 T521C polymorphism and methotrexate-induced hepatotoxicity. We performed a systematic review of previous reports from the PubMed, Web of Science, and EMBASE databases, and a meta-analysis was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated to evaluate the effect of the SLCO1B1 T521C polymorphism on the occurrence of methotrexate-induced hepatotoxicity. In total, data from five studies including 465 patients were analyzed. Patients had received a high-dose methotrexate regimen (1-5 g/m2). The SLCO1B1 variant allele (C allele) carriers had a 1.9-fold higher risk of hepatotoxicity than wild-type homozygote carriers (TT; OR, 1.94; 95% CI, 1.14-3.31). This meta-analysis demonstrated that C allele carriers of the SLCO1B1 polymorphism had a higher risk of hepatotoxicity than patients with the TT genotype. The SLCO1B1 T521C polymorphism may be a useful predictor for methotrexate-induced hepatotoxicity in patients with malignancies.
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Antimetabólitos Antineoplásicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/genética , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Metotrexato/efeitos adversos , Alelos , Antimetabólitos Antineoplásicos/uso terapêutico , Relação Dose-Resposta a Droga , Humanos , Metotrexato/uso terapêutico , Neoplasias/tratamento farmacológico , Polimorfismo Genético , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
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.
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Background: Although nilotinib hepatotoxicity can cause severe clinical conditions and may alter treatment plans, risk factors affecting nilotinib-induced hepatotoxicity have not been investigated. This study aimed to elucidate the factors affecting nilotinib-induced hepatotoxicity. Methods: This retrospective cohort study was performed on patients using nilotinib from July of 2015 to June of 2020. We estimated the odds ratio and adjusted odds ratio from univariate and multivariate analyses, respectively. Several machine learning models were developed to predict risk factors of hepatotoxicity occurrence. The area under the curve (AUC) was analyzed to assess clinical performance. Results: Among 353 patients, the rate of patients with grade I or higher hepatotoxicity after nilotinib administration was 40.8%. Male patients and patients who received nilotinib at a dose of ≥300 mg had a 2.3-fold and a 3.5-fold increased risk for hepatotoxicity compared to female patients and compared with those who received <300 mg, respectively. H2 blocker use decreased hepatotoxicity by 11.6-fold. The area under the curve (AUC) values of machine learning methods ranged between 0.61-0.65 in this study. Conclusion: This study suggests that the use of H2 blockers was a reduced risk of nilotinib-induced hepatotoxicity, whereas male gender and a high dose were associated with increased hepatotoxicity.
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Fígado/efeitos dos fármacos , Aprendizado de Máquina , Pirimidinas/efeitos adversos , Medição de Risco/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Área Sob a Curva , Doença Hepática Induzida por Substâncias e Drogas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/farmacologia , Estudos Retrospectivos , Risco , Fatores de Risco , Adulto JovemRESUMO
Although hepatotoxicity induced by immune checkpoint inhibitors (ICPIs) can cause severe clinical complications, the risk factors associated with hepatotoxicity have rarely been investigated. The purpose of this study was to determine the potential risk factors for the incidence of hepatotoxicity and for time to ICPI-induced hepatotoxicity. Patients who received ICPIs (atezolizumab, nivolumab, pembrolizumab, and ipilimumab) were included in this retrospective 2-center study. Collected data included sex, age, body weight, body surface area, Eastern Cooperative Oncology Group performance status, underlying disease, liver metastasis, programmed cell death ligand-1 expression, interval from previous chemotherapy, and concomitant drug use. Among the 194 patients, patients who experienced hepatotoxicity after ICPI administration was 64.4% (n=125) in all grade and 10.8% (n=21) in grade III or higher. Multivariate analysis showed that patients aged 30-50 and 50-70 years had increased risks of hepatotoxicity by 4.9-fold (95% confidence interval, 1.3-18.0) and 2.7-fold (95% confidence interval, 1.3-5.5), respectively, compared with those older than 70 years. The use of acetaminophen increased the occurrence of hepatotoxicity by 2.1 times; the attributable risk was 53.2%. Male patients and patients younger than 65 years had around 1.5-fold increased hazard of time to reach hepatotoxicity. Patients treated with 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors had a 4.7-fold higher risk of grade III-IV hepatotoxicity compared with those without HMG-CoA reductase inhibitors; the attributable risk was 78.8%. In conclusion, close monitoring of liver function is recommended, especially in male patients, patients younger than 65 years old, and when there is concomitant use of hepatotoxic drugs including acetaminophen and HMG-CoA reductase inhibitors.
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Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Fatores Sexuais , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Hepáticas , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: The dose response relationship of nine-year cumulative anticholinergic exposure and dementia onset was investigated using the Korean version anticholinergic burden scale (KABS) in comparison with the Anticholinergic Cognitive Burden Scale (ACB). We also examined the effect of weak anticholinergics in the prediction of dementia. METHODS: A retrospective case-control study was conducted comprising 86,576 patients after 1:2 propensity score matching using the longitudinal national claims database. For cumulative anticholinergic burden estimation, average daily anticholinergic burden score during the 9 years prior to dementia onset was calculated using KABS and ACB and categorized as minimal, < 0.25; low, 0.25-1; intermediate, 1-2; and high, ≥ 2. Adjusted odds ratio (aOR) between cumulative anticholinergic burden and incident dementia was estimated. RESULTS: Patients with high exposure according to KABS and ACB comprised 3.2 and 3.4% of the dementia cohort and 2.1 and 2.8% of the non-dementia cohort, respectively. Dose-response relationships were observed between anticholinergic burden and incident dementia. After adjusting covariates, compared with minimal exposure, patients with high exposure according to KABS and ACB had a significantly higher risk for incident dementia with aOR of 1.71 (95% confidence interval (CI) 1.55-1.87) and 1.22 (CI 1.12-1.33), respectively. With the exclusion of weak anticholinergics, the association became stronger, i.e., 1.41 (CI 1.14-1.75) with ACB whereas the association became slightly weaker with KABS, i.e., 1.60 (CI 1.38-1.86). CONCLUSION: This study confirmed the dose response relationship for cumulative anticholinergic burden measured using the Korean specific anticholinergic burden scale with incident dementia.
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Antagonistas Colinérgicos , Demência , Estudos de Casos e Controles , Antagonistas Colinérgicos/efeitos adversos , Demência/induzido quimicamente , Demência/diagnóstico , Demência/epidemiologia , Humanos , República da Coreia/epidemiologia , Estudos RetrospectivosRESUMO
Background and Objectives: Recent evidence suggests that oral health is associated with various systemic diseases including psychiatric illnesses. This study examined the association between depression and access to dental care in Korean adults. Materials and Methods: A cross-sectional evaluation was performed using data from the Sixth Korea National Health and Nutrition Examination Survey 2014. The general characteristics of the participants, the current depression status, and issues with access to dental care were collected to evaluate the factors for not being able to make dental visits according to care needs. Results: The study population comprised a total of 5976 participants who were 19 years of age and older and represented 40.7 million Koreans. A multivariable logistic regression analysis with weighted observations revealed that participants with current depressive illness were about two times more likely to express that they could not make dental visits in spite of their perceived care needs (adjusted odds ratio (OR) = 2.097; 95% confidence interval (CI) 1.046-4.203). The reasons for not making dental visits included financial problems, perceived importance of the dental problem, and fear of visiting dental professionals. Conclusions: Korean adults with current depressive illness were less likely to make dental visits when they had dental care needs. To improve dental health accessibility for patients with depressive illness, coordinated efforts can be considered involving multidisciplinary health care professionals.
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Assistência Odontológica/estatística & dados numéricos , Depressão/epidemiologia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Adulto , Idoso , Estudos Transversais , Assistência Odontológica/psicologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Bucal/estatística & dados numéricos , República da Coreia/epidemiologiaRESUMO
Emerging studies suggest that microRNAs (miRNAs) play multiple roles in cancer malignancy, including proliferation and acquisition of metastatic potential. Differentially expressed miRNAs responsible for the malignancy of lung cancer were searched by miRNA microarray using a previously established brain metastatic lung cancer model. Twenty-five miRNAs were down-regulated in brain metastatic lung cancer cells. Among those, miR-193b-3p and -5p were chosen for further studies. Their function in metastatic potential and proliferation was examined using Transwell invasion, wound healing, and colony forming assays. The underlying mechanism of tumor-suppressor miR-193b-3p and -5p was explored using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), Western blot, Argonaute 2-RNA immunoprecipitation (Ago2-RIP), and reporter assays. Both strands of miR-193b were down-regulated in brain metastatic lung cancer cells and in tissues from lung cancer patients. Overexpression of miR-193b-3p and -5p inhibited invasive and migratory activities and diminished clonogenic ability. Conversely, inhibition of miR-193b-3p or -5p increased the metastatic potential and colony forming ability. Cyclin D1 (CCND1), Ajuba LIM Protein (AJUBA), and heart development protein with EGF like domains 1 (HEG1) were identified as common target genes of miR-193b-3p and -5p. A reporter assay and an Ago2-RIP experiment showed that both miRNAs directly bind to the 3' untranslated region (3'UTR) of the target mRNA. Knockdown of target gene reduced the proliferative and metastatic potential of primary and metastatic lung cancer cells. Our results demonstrate miR-193b is a dual-strand tumor suppressor and a novel therapeutic target for lung cancer.
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Genes Supressores de Tumor , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , RNA Neoplásico/metabolismo , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Linhagem Celular Tumoral , Ciclina D1/genética , Ciclina D1/metabolismo , Humanos , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Metástase Neoplásica , RNA Neoplásico/genéticaRESUMO
BACKGROUND: Hematological abnormalities after transplantation are complications that may arise after renal transplantation, of which thrombocytopenia is associated with increased risk of bleeding and other complications. The development of thrombocytopenia is affected by various clinical conditions, and the stromal-derived factor 1 (SDF1) and platelet factor 4 (PF4) genes are known to be involved in the production or destruction of platelets. The purpose of this study was to investigate the prevalence of posttransplant thrombocytopenia and its association with other clinical conditions and genetic polymorphisms of SDF1 and PF4 genes a long time after transplantation. METHODS: This is a retrospective study that includes a total of 305 kidney transplant (KT) recipients between 2008 and 2012 at St. Vincent Medical Center, Los Angeles, CA. In this study, posttransplant thrombocytopenia was defined as a 30% reduction in platelet count from the baseline in the first week or a decrease of <100 (×103/µL) within 1â¯year after KT. The subjects were divided into posttransplant thrombocytopenia and control groups. The chi-square test, t-test, and logistic regression were used for the analyses. RESULTS: In the first week, 65 patients had a 30% reduction in platelet count (21.3%). Gender, simultaneous kidney-pancreas transplantation, induction therapy (IT), and only alleles of rs2297630 of SDF1, among the SDF1 and PF4 genes, showed statistically significant differences. The rs2297630 alleles were consistently significant risk factors (non G vs. G: odds ratioâ¯=â¯0.445; 95% confidence interval, 0.224-0.884; pâ¯=â¯.021) in the multiple logistic regression. In the 1-year study, 61 patients (20.0%) had platelet counts of <100â¯×â¯103/µL and had statistically significant differences in patients who had delayed graft function and induction therapy. CONCLUSIONS: In this study, non-G group of rs2297630 in SDF1 significantly increased the risk of post-transplant thrombocytopenia in the first week of kidney transplantation.
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Alelos , Quimiocina CXCL12/genética , Transplante de Rim , Fator Plaquetário 4/genética , Polimorfismo Genético , Trombocitopenia/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia , Fatores de TempoRESUMO
This study aimed to determine the level of pharmacovigilance (PV) education in pharmacy programmes and to evaluate the predictive factors for the intent to report adverse drug reactions (ADRs) by pharmacy students in South Korea. Self-administered questionnaires were collected from a regionally stratified nationwide convenience sample of pharmacy students in September 2017. The association between students' intent to report ADRs and their knowledge and attitude was evaluated by using multivariate logistic regression analysis. In total, 303 pharmacy students participated in the survey; the average age of students was 26.7 (standard deviation 2.9) years and 40.6% were males. Eighty-eight students (29%) marked the degree of their intent as "strongly high." Increased knowledge of ADR reporting methods and positive attitude towards the need for ADR reporting were significant predictors of the intent to report ADRs. Further, witnessing reporting by the preceptor (adjusted odds ratio, 2.37; 95% confidence interval, 1.26-4.46; P < 0.01) was significantly correlated with the knowledge on and attitude towards ADR reporting of pharmacy students. The findings of our study indicated the need for improvements in PV curriculum, such as educational content focused on ADR reporting methods and demonstration of a preceptor's reporting in pharmacy practice experiential rotation, within Korean college of pharmacy curriculum.
Assuntos
Educação em Farmácia/métodos , Farmacovigilância , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Atitude do Pessoal de Saúde , Estudos Transversais , Currículo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Masculino , República da Coreia , Estudantes de Farmácia , Inquéritos e Questionários , Adulto JovemRESUMO
The aim of this study was to introduce the newly developed micro-locking implant prosthetic system and to evaluate the resulting its characteristics. To evaluate load-bearing capacity, 25 implants were divided into five groups: external-hexagon connection (EH), internal-octagon connection (IO), internal-hexagon connection (IH), one-body implant (OB), micro-locking implant system (ML). The maximum compressive load was measured using a universal testing machine (UTM) according to the ISO 14801. Retention was evaluated in two experiments: (1) a tensile test of the structure modifications of the components (attachment and implant) and (2) a tensile test after cyclic loading (total 5,000,000 cycles, 100 N, 2 Hz). The load-bearing capacity of the ML group was not significantly different from the other groups (p > 0.05). The number of balls in the attachment and the presence of a hexagonal receptacle did not show a significant correlation with retention (p > 0.05), but the shape of the retentive groove in the implant post had a statistically significant effect on retention (p < 0.05). On the other hand, the retention loss was observed during the initial 1,000,000 cycles, but an overall constant retention was maintained afterward. Various preclinical studies on this novel micro-locking implant prosthetic system should continue so that it can be applied in clinical practice.