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OBJECTIVE: Previous research using the National Health and Aging Trends Study showed that a claims-based frailty index (CFI) could be useful for identifying moderate-to-severe dementia in Medicare claims data. This study aims to validate the findings in an independent cohort. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: The study included 658 fee-for-service beneficiaries with dementia who participated in the 2016-2020 Medicare Current Beneficiary Survey in the community-dwelling. METHODS: We operationalized the Functional Assessment Staging Test (FAST) scale (range: 1-7, stages 5-7 indicate moderate-to-severe dementia) using survey information. CFI (range: 0-1, higher scores indicate greater frailty) was calculated using Medicare claims 12 months before the participants' interview date. Using the previously proposed cut point of 0.280, we calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying moderate-to-severe dementia. Survey procedures were used to account for survey design and weighted to reflect national estimates. RESULTS: The population had a mean age (SD) of 80.7 (8.9) years, 58.5% female, and 101 beneficiaries (14.8%) had moderate-to-severe dementia. The CFI cut point of 0.280 demonstrated sensitivity 0.49 (95% CI, 0.38-0.59), specificity 0.80 (0.77-0.84), PPV 0.30 (0.23-0.38), and NPV 0.90 (0.87-0.93). Compared with those with a CFI <0.280, beneficiaries with a CFI ≥0.280 had an elevated risk of mortality (2.9% vs 4.1%) over 1 year. CONCLUSIONS AND IMPLICATIONS: These results confirm our previous findings that CFI among beneficiaries with a dementia diagnosis is a useful measure of moderate-to-severe dementia for Medicare claims data.
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BACKGROUND AND OBJECTIVES: A comprehensive survey of congenital heart disease (CHD) prevalence has not yet been conducted in South Korea. This study aimed to investigate the prevalence of CHDs in Korean children and lay the foundation for national CHD epidemiology. METHODS: Target patients were infantile crucial CHDs, which include critical CHDs (requiring urgent procedures after birth with common hypoxemic defects) and diverse categorical defects excluding simple shunt defects. Data were obtained from the National Health Insurance Service over a 5-year period (2014-2018). Birth prevalence (new cases per 1,000 live births) of CHDs in Korea was analyzed and compared with that of other countries. RESULTS: The birth prevalences of right heart obstructive defects (pulmonary valve stenosis and pulmonary atresia), conus anomalies (tetralogy of Fallot and double outlet right ventricle), and total anomalous pulmonary venous return showed significant increases in the East Asian group (P < 0.001), whereas those of left heart obstructive defects (coarctation of aorta, aortic stenosis, and hypoplastic left heart syndrome), truncus anomalies (D-transposition of great artery and persistent truncus arteriosus), atrioventricular septal defect, and hypoplastic right heart syndrome were significantly decreased in the East Asian group (P < 0.001). CONCLUSIONS: The overall birth prevalence of crucial CHDs in Korea was similar to that of critical CHDs in previous studies from other countries. Some subtypes of right heart obstructive defects, left heart obstructive defects, and conotruncal anomalies showed significant differences between East Asian and Western populations. This study contributes to a foundation for national CHD epidemiology in Korean children.
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The objective of this review is to summarize and appraise the research methodology, emerging findings, and future directions in pharmacoepidemiologic studies assessing the benefits and harms of pharmacotherapies in older adults with different levels of frailty. Older adults living with frailty are at elevated risk for poor health outcomes and adverse effects from pharmacotherapy. However, current evidence is limited due to the under-enrollment of frail older adults and the lack of validated frailty assessments in clinical trials. Recent advancements in measuring frailty in administrative claims and electronic health records (database-derived frailty scores) have enabled researchers to identify patients with frailty and to evaluate the heterogeneity of treatment effects by patients' frailty levels using routine health care data. When selecting a database-derived frailty score, researchers must consider the type of data (e.g., different coding systems), the length of the predictor assessment period, the extent of validation against clinically validated frailty measures, and the possibility of surveillance bias arising from unequal access to care. We reviewed 13 pharmacoepidemiologic studies published on PubMed from 2013 to 2023 that evaluated the benefits and harms of cardiovascular medications, diabetes medications, anti-neoplastic agents, antipsychotic medications, and vaccines by frailty levels. These studies suggest that, while greater frailty is positively associated with adverse treatment outcomes, older adults with frailty can still benefit from pharmacotherapy. Therefore, we recommend routine frailty subgroup analyses in pharmacoepidemiologic studies. Despite data and design limitations, the findings from such studies may be informative to tailor pharmacotherapy for older adults across the frailty spectrum.
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Fragilidade , Farmacoepidemiologia , Humanos , Farmacoepidemiologia/métodos , Idoso , Idoso Fragilizado , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologiaRESUMO
BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) introduced chronic care management (CCM) services in 2015 for patients with multiple chronic diseases. Few studies examine the utilization of CCM services by geographic region, sociodemographic, and clinical characteristics. METHODS: We used 2014-2019 Medicare claims data from a 5% random sample of fee-for-service beneficiaries aged 65 years or over. We included beneficiaries potentially eligible for CCM services because they had multiple chronic conditions (1,073,729 in 2015 and 1,130,523 in 2019). We calculated the proportion of potentially eligible beneficiaries receiving CCM service each year for the total population and by geographic region, sociodemographic, and clinical characteristics. RESULTS: The proportion of beneficiaries with two or more chronic conditions receiving CCM services increased from 1.1% in 2015 to 3.4% in 2019. The increase in CCM use was higher in the southern region, among dually eligible beneficiaries and beneficiaries with a greater burden of chronic conditions (2-5 conditions vs ≥10 conditions: 0.7% vs 2.0% in 2015; 2.1% vs 7.0% in 2019) and frailty (robust vs severely frail: 0.6% vs 3.3% in 2015; 1.9% vs 9.4% in 2019). Nearly one out of five recipients did not continue CCM service after the initial service. CONCLUSION: We found that CCM service is being used by a very small fraction of eligible patients. Barriers and facilitators to more effective CCM adoption should be identified and incorporated into strategies that encourage more widespread use of this Medicare benefit.
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Perillyl alcohol (POH) is a secondary metabolite of plants. POH and its derivatives are known to be effective as an anticancer treatment. In this study, oxidative derivatives of POH, which are difficult to synthesize chemically, were synthesized using the engineered bacterial cytochrome P450 BM3 (CYP102A1) as a biocatalyst. The activity of wild-type (WT) CYP102A1 and 29 engineered enzymes toward POH was screened using a high-performance liquid chromatography. They produced one major product. Among them, the engineered CYP102A1 M601 mutant with seven mutations (R47L/F81I/F87V/E143G/L150F/L188Q/E267V) showed the highest conversion, 6.4-fold higher than the WT. Structure modeling using AlphFold2 and PyMoL suggests that mutations near the water channel may be responsible for the increased catalytic activity of the M601 mutant. The major product was identified as a POH-8,9-epoxide by gas chromatography-mass spectrometry and nuclear magnetic resonance analysis. The optimal temperature and pH for the product formation were 35 °C and pH 7.4, respectively. The kcat and Km of M601 were 540â¯min-1 and 2.77â¯mM, respectively. To improve POH-8,9-epoxide production, substrate concentration and reaction time were optimized. The optimal condition for POH-8,9-epoxide production by M601 was 5.0â¯mM POH, pH 7.4, 35 â, and 6â¯h reaction, which produced the highest concentration of 1.72â¯mM. Therefore, the biosynthesis of POH-8,9-epoxide using M601 as a biocatalyst is suggested to be an efficient and sustainable synthetic process that can be applied to chemical and pharmaceutical industries.
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BACKGROUND: Sleep aids are commonly prescribed to treat sleep disturbance, a modifiable risk factor for postoperative delirium in older patients. The use of melatonin receptor agonists in the postoperative period has been increasing. The comparative safety of melatonin receptor agonists, zolpidem, and temazepam remains uncertain. METHODS: This retrospective study included 22,083 patients ≥65 years old who initiated melatonin receptor agonists, zolpidem, or temazepam after major surgery in the Premier Healthcare Database 2009-2018. We performed propensity score-based overlap weighting and estimated the risk ratio (RR) and risk difference (RD) of postoperative delirium as the primary outcome and a composite of delirium or new antipsychotic initiation, pneumonia, and in-hospital mortality as secondary outcomes. RESULTS: The mean age of the study population was 78 (SD, 7) years and 50% were female. There was no significant difference in the risk of postoperative delirium among patients treated with melatonin receptor agonists (3.4%, reference group), zolpidem (2.9%; RR [95% CI], 0.9 [0.7-1.2]; RD [95% CI] per 100 persons, -0.3 [-1.1 to 0.6]), and temazepam (3.1%; 0.9 [0.7-1.1]; RD [95% CI] per 100 persons, -0.5 [-1.2 to 0.3]). The risks of delirium or new antipsychotic initiation, pneumonia, and in-hospital mortality were also similar among all groups. CONCLUSIONS: Melatonin receptor agonists were not associated with a lower risk of postoperative delirium and other adverse outcomes compared with zolpidem and temazepam in older adults after major surgery.
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PURPOSE: This study aimed to identify research trends related to emotional leadership among nurse managers by conducting a systematic literature review and meta-analysis. This study sought to derive insights that could contribute to improving emotional leadership in nursing practice. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Databases including PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, Web of Science, Research Information Sharing Service, Koreanstudies Information Service System, Korean Medical Database, KoreaMed, ScienceON, and DBpia were searched to obtain papers published in English and Korean. Literature searches and screenings were conducted for the period December 1, 2023 to December 17, 2023. The effect size correlation (ESr) was calculated for each variable and the meta-analysis was performed using the statistical software SPSS 29.0, R 4.3.1. RESULTS: Twenty-five (four personal, six job, and fifteen organizational) relevant variables were identified through the systematic review. The results of the meta-analysis showed that the total overall effect size was ESr = .33. Job satisfaction (ESr = .40) and leader-member exchange (ESr = .75) had the largest effect size among the job and organizational-related factors. CONCLUSION: Emotional leadership helps promote positive changes within organizations, improves organizational effectiveness, and increases member engagement and satisfaction. Therefore, it is considered an important strategic factor in improving organizational performance.
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Emoções , Satisfação no Emprego , Liderança , Enfermeiros Administradores , Humanos , Bases de Dados Factuais , Enfermeiros Administradores/psicologiaRESUMO
BACKGROUND: Understanding how patients' frailty and the physiological stress of surgical procedures affect postoperative outcomes may inform risk stratification of older patients undergoing surgery. The objective of the study was to examine the association of peri-operative frailty with mortality, 30-day readmission and days at home after non-cardiac surgical procedures of different physiological stress. METHODS: This retrospective study used Medicare claims data from a 7.125% random sample of Medicare fee-for-service beneficiaries from 2015 to 2019 who were aged ≥ 65 years and underwent non-cardiac surgical procedure listed in the Operative Stress Score categories. The exposure of the study was claims-based frailty index (robust, < 0.15; pre-frail, 0.15 to < 0.25; mildly frail, 0.25 to < 0.35; and moderate-to-severely frail, ≥ 0.35) with Operative Stress Score categories being 1, very low stress to 5, very high stress. The primary outcome was all-cause mortality at 30 days and 365 days after the surgical procedure. RESULTS: In total, 1,019,938 patients (mean (SD) age of 76.1 (7.3) years; 52.3% female; 16.8% frail) were included. The cumulative incidence of mortality generally increased with Operative Stress Score category, ranging from 5.0% (Operative Stress Score 2) to 24.9% (Operative Stress Score 4) at 365 days. Within each category, increasing frailty was associated with mortality at 30 days (hazard ratio comparing moderate-to-severe frailty vs. robust ranged from 1.59-3.91) and at 365 days (hazard ratio 1.30-4.04). The variation in postoperative outcomes by patients' frailty level was much greater than the variation by the operative stress category. CONCLUSIONS: These results emphasise routine frailty screening before major and minor non-cardiac procedures and the need for greater clinician awareness of postoperative outcomes beyond 30 days in shared decision-making with older adults with frailty.
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Fragilidade , Medicare , Readmissão do Paciente , Humanos , Feminino , Idoso , Masculino , Estados Unidos/epidemiologia , Estudos Retrospectivos , Readmissão do Paciente/estatística & dados numéricos , Fragilidade/mortalidade , Idoso de 80 Anos ou mais , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Alta do Paciente/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/mortalidade , Estresse Fisiológico , Idoso Fragilizado/estatística & dados numéricosRESUMO
Medication is a potential factor influencing frailty. However, the relationship between pharmaceutical treatments and frailty remains unclear. Therefore, we conducted the present systematic review to summarize the association between drug therapy and the risk of incident frailty in older adults. We systematically searched the MEDLINE electronic database for articles indexed between January 1, 2000, and December 31, 2021, for randomized controlled trials (RCTs) and cohort studies reporting frailty changes associated with drug therapy. A total of 6 RCTs and 13 cohort studies involving 211,948 participants were identified, and their treatments were categorized into six medication classes: analgesics, cardiometabolic medication, chemotherapy, central nervous system (CNS)-active medication, hormonal therapy, and nutritional supplements. While the analysis revealed that only CNS-active medications were associated with an elevated risk of frailty, other medication classes also affected frailty; however, this is not conclusively attributable to a class-wide effect.
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CYP102A1 from Bacillus megaterium is an important enzyme in biotechnology, because engineered CYP102A1 enzymes can react with diverse substrates and produce human cytochrome P450-like metabolites. Therefore, CYP102A1 can be applied to drug metabolite production. Terpinen-4-ol is a cyclic monoterpene and the primary component of essential tea tree oil. Terpinen-4-ol was known for therapeutic effects, including antibacterial, antifungal, antiviral, and anti-inflammatory. Because terpenes are natural compounds, examining novel terpenes and investigating the therapeutic effects of terpenes represent responses to social demands for eco-friendly compounds. In this study, we investigated the catalytic activity of engineered CYP102A1 on terpinen-4-ol. Among CYP102A1 mutants tested here, the R47L/F81I/F87V/E143G/L188Q/N213S/E267V mutant showed the highest activity to terpinen-4-ol. Two major metabolites of terpinen-4-ol were generated by engineered CYP102A1. Characterization of major metabolites was confirmed by liquid chromatography-mass spectrometry (LC-MS), gas chromatography-MS, and nuclear magnetic resonance spectroscopy (NMR). Based on the LC-MS results, the difference in mass-to-charge ratio of an ion (m/z) between terpinen-4-ol and its major metabolites was 16. One major metabolite was defined as 1,4-dihydroxy-p-menth-2-ene by NMR. Given these results, we speculate that another major metabolite is also a mono-hydroxylated product. Taken together, we suggest that CYP102A1 can be applied to make novel terpene derivatives.
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Sistema Enzimático do Citocromo P-450 , Terpenos , Humanos , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Terpenos/química , Monoterpenos , NADPH-Ferri-Hemoproteína Redutase/genética , NADPH-Ferri-Hemoproteína Redutase/metabolismoRESUMO
BACKGROUND: Professional society guidelines recommend limiting the use of antipsychotics in older patients with postoperative delirium. How these recommendations affected the use of antipsychotics and other psychoactive drugs in the postoperative period has not been studied. METHODS: This retrospective cohort study included patients 65 years or older without psychiatric diagnoses who underwent major surgery in community hospitals (CHs) and academic medical centers (AMCs) in the United States. The outcome was the rate of hospital days exposed to antipsychotics, antidepressants, antiepileptics, benzodiazepines, hypnotics, and selective alpha-2 receptor agonist dexmedetomidine in the postoperative period by hospital type. RESULTS: The study included 4,098,431 surgical admissions from CHs (mean age 75.0 [standard deviation, 7.1] years; 50.8% female) during 2008-2018 and 2,310,529 surgical admissions from AMCs (75.0 [7.4] years; 49.4% female) during 2009-2018. In the intensive care unit (ICU) setting, the number of exposed days per 1000 hospital-days declined for haloperidol (CHs: 33-21 days [p < 0.01]; AMCs: 24-15 days [p < 0.01]) and benzodiazepines (CHs: 261-136 days [p < 0.01]; AMCs: 150-77 days [p < 0.01]). The use of atypical antipsychotics, antidepressants, antiepileptics, and dexmedetomidine increased, while hypnotic use varied by the hospital type. In the non-ICU setting, the rate declined for haloperidol in CHs but not in AMCs (CHs: 10-6 days [p < 0.01]; AMCs: 4-3 days [p = 0.52]) and for benzodiazepines in both settings (CHs: 126-56 days [p < 0.01]; AMCs: 30-27 days [p < 0.01]). The use of antiepileptics and antidepressants increased, while the use of atypical antipsychotics and hypnotics varied by the hospital type. CONCLUSIONS: The use of haloperidol and benzodiazepines in the postoperative period declined at both CHs and AMCs. These trends coincided with the increasing use of other psychoactive drugs.
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Antipsicóticos , Dexmedetomidina , Humanos , Feminino , Estados Unidos , Idoso , Masculino , Antipsicóticos/uso terapêutico , Haloperidol , Estudos Retrospectivos , Anticonvulsivantes , Psicotrópicos/uso terapêutico , Benzodiazepinas/efeitos adversos , Hipnóticos e Sedativos , AntidepressivosRESUMO
BACKGROUND: Intensive blood pressure lowering prevents major adverse cardiovascular events, but some patients experience serious adverse events. Examining benefit-harm profiles may be more informative than analyzing major adverse cardiovascular events and serious adverse events separately. METHODS: We analyzed data from the Systolic Blood Pressure Intervention Trial (n = 9361), comparing intensive treatment (systolic blood pressure target <120 mm Hg) to standard treatment (<140 mm Hg). A 4-year hierarchical outcome profile was defined for each participant: 1) alive with neither major adverse cardiovascular events nor serious adverse events (most desirable); 2) alive with serious adverse events only; 3) alive with major adverse cardiovascular events only; 4) alive with both events; and 5) deceased (least desirable). We compared 4-year outcome profiles between the treatment groups in the entire population and by frailty subgroups defined using physical frailty phenotype (non-frail, pre-frail, and frail). RESULTS: The proportion who died were lower with intensive treatment than standard treatment (5% vs 6%). A higher proportion of the intensive treatment group was alive with serious adverse events and no major adverse cardiovascular events (36% vs 33%), and a lower proportion were alive with both events (6% vs 5%) than the standard treatment group. The outcome profiles were more favorable among those with physical frailty phenotype who were treated with intensive treatment vs standard treatment, but outcome profiles were similar between the treatment groups among non-frail or pre-frail participants. CONCLUSIONS: This post hoc proof-of-concept analysis demonstrates the utility of the outcome profile analysis that simultaneously examines the benefit and harm of the treatment.
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Fragilidade , Hipertensão , Humanos , Pressão Sanguínea , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/efeitos adversos , Determinação da Pressão ArterialRESUMO
BACKGROUND: Antipsychotics are commonly used to manage postoperative delirium. Recent studies reported that haloperidol use has declined, and atypical antipsychotic use has increased over time. OBJECTIVE: To compare the risk for in-hospital adverse events associated with oral haloperidol, olanzapine, quetiapine, and risperidone in older patients after major surgery. DESIGN: Retrospective cohort study. SETTING: U.S. hospitals in the Premier Healthcare Database. PATIENTS: 17 115 patients aged 65 years and older without psychiatric disorders who were prescribed an oral antipsychotic drug after major surgery from 2009 to 2018. INTERVENTIONS: Haloperidol (≤4 mg on the day of initiation), olanzapine (≤10 mg), quetiapine (≤150 mg), and risperidone (≤4 mg). MEASUREMENTS: The risk ratios (RRs) for in-hospital death, cardiac arrhythmia events, pneumonia, and stroke or transient ischemic attack (TIA) were estimated after propensity score overlap weighting. RESULTS: The weighted population had a mean age of 79.6 years, was 60.5% female, and had in-hospital death of 3.1%. Among the 4 antipsychotics, quetiapine was the most prescribed (53.0% of total exposure). There was no statistically significant difference in the risk for in-hospital death among patients treated with haloperidol (3.7%, reference group), olanzapine (2.8%; RR, 0.74 [95% CI, 0.42 to 1.27]), quetiapine (2.6%; RR, 0.70 [CI, 0.47 to 1.04]), and risperidone (3.3%; RR, 0.90 [CI, 0.53 to 1.41]). The risk for nonfatal clinical events ranged from 2.0% to 2.6% for a cardiac arrhythmia event, 4.2% to 4.6% for pneumonia, and 0.6% to 1.2% for stroke or TIA, with no statistically significant differences by treatment group. LIMITATION: Residual confounding by delirium severity; lack of untreated group; restriction to oral low-to-moderate dose treatment. CONCLUSION: These results suggest that atypical antipsychotics and haloperidol have similar rates of in-hospital adverse clinical events in older patients with postoperative delirium who receive an oral low-to-moderate dose antipsychotic drug. PRIMARY FUNDING SOURCE: National Institute on Aging.
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Antipsicóticos , Delírio do Despertar , Ataque Isquêmico Transitório , Humanos , Feminino , Idoso , Masculino , Antipsicóticos/efeitos adversos , Fumarato de Quetiapina/efeitos adversos , Haloperidol/efeitos adversos , Olanzapina , Risperidona , Estudos de Coortes , Mortalidade Hospitalar , Estudos Retrospectivos , HospitaisRESUMO
Purpose: This study aims to identify unmet needs and barriers for improving inpatient care for older adults at an academic hospital in Korea by using a qualitative focus group design and the Age-Friendly Health Systems (AFHS) framework. Patients and Methods: A total of 14 healthcare providers and employees participated in focus group interviews. Participants included medical doctors, registered nurses, a receptionist, a patient transporter, a pharmacist, a physical therapist, and a social worker. The data were analyzed qualitatively, as per the Consolidated Criteria for Reporting Qualitative Research guidelines. The analysis method encompassed a thematic framework analysis via the AFHS 4Ms framework, consisting of the four domains "What Matters", "Medication", "Mentation", and "Mobility". Results: Multiple barriers and unmet needs were identified using the AFHS 4Ms framework in the provision of inpatient care for older adults at the hospital. The main barriers identified in the "What matters" domain are a lack of shared decision-making and individualized care plans, as well as economic and safety-conscious preferences among some older patients. In the "Medications" domain, the main barriers to providing adequate and safe pharmacotherapy include patient and caregiver-related factors, increased complexity of medication use, and lack of institutional support systems. In the "Mentation" domain, the main issues identified are communication barriers related to patients, caregiver factors, and insufficient delirium management due to a lack of adequate processes/environments such as delirium identification. In the "Mobility" domain, the main challenges include reduced mobility and geriatric complications, unnecessary mobility restrictions, and the increased risk of falls due to lack of resources and environmental factors. Conclusion: The study highlighted the need for improvements in inpatient care for older adults at an academic hospital in Korea. Identified unmet needs and barriers can be used to guide a more patient-centered approaches for an age-friendly inpatient environment.
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Delírio , Pessoal de Saúde , Humanos , Idoso , Pesquisa Qualitativa , Grupos Focais , HospitaisRESUMO
BACKGROUND: Dementia severity is unavailable in administrative claims data. We examined whether a claims-based frailty index (CFI) can measure dementia severity in Medicare claims. METHODS: This cross-sectional study included the National Health and Aging Trends Study Round 5 participants with possible or probable dementia whose Medicare claims were available. We estimated the Functional Assessment Staging Test (FAST) scale (range: 3 [mild cognitive impairment] to 7 [severe dementia]) using information from the survey. We calculated CFI (range: 0-1, higher scores indicating greater frailty) using Medicare claims 12 months prior to the participants' interview date. We examined C-statistics to evaluate the ability of the CFI in identifying moderate-to-severe dementia (FAST stage 5-7) and determined the optimal CFI cut-point that maximized both sensitivity and specificity. RESULTS: Of the 814 participants with possible or probable dementia and measurable CFI, 686 (72.2%) patients were ≥75 years old, 448 (50.8%) were female, and 244 (25.9%) had FAST stage 5-7. The C-statistic of CFI to identify FAST stage 5-7 was 0.78 (95% confidence interval: 0.72-0.83), with a CFI cut-point of 0.280, achieving the maximum sensitivity of 76.9% and specificity of 62.8%. Participants with CFI ≥0.280 had a higher prevalence of disability (19.4% vs 58.3%) and dementia medication use (6.0% vs 22.8%) and higher risk of mortality (10.7% vs 26.3%) and nursing home admission (4.5% vs 10.6%) over 2 years than those with CFI <0.280. CONCLUSIONS: Our study suggests that CFI can be useful in identifying moderate-to-severe dementia from administrative claims among older adults with dementia.
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Demência , Fragilidade , Humanos , Feminino , Idoso , Estados Unidos/epidemiologia , Masculino , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Estudos Transversais , Medicare , Idoso Fragilizado , Demência/diagnóstico , Demência/epidemiologia , Demência/tratamento farmacológicoRESUMO
Introduction: The study aimed to demonstrate the risk factors for fractures and to develop prediction models for major osteoporotic and hip fractures in osteopenic patients using the nationwide cohort study in South Korea. Methods: The study was a retrospective nationwide study using the national screening program for transitional ages from the National Health Insurance Services database in Korea from 2008 to 2019. Primary outcomes were incident fracture events of major osteoporotic and hip fractures. Major osteoporotic and hip fracture events were defined as diagnostic and procedural codes. Patients were followed until the fragility fractures, death, or 2019, whichever came first. Results: All participants were 66-year-old females, with a mean body mass index was 25.0 ± 3.1 kg/m2. During a median follow-up of 10.5 years, 26.9% and 6.7% of participants experienced major osteoporotic and hip fractures. In multivariate analysis, a history of fracture, chronic airway disease, falls, diabetes mellitus and cerebrovascular diseases were significant risk factors for major osteoporotic (hazard ratio [HR] 2.35 for a history of fracture; 1.17 for chronic airway disease; 1.10 for falls; 1.12 for diabetes mellitus; 1.11 for cerebrovascular disease) and hip fractures (HR 1.75 for a history of fracture; 1.54 for diabetes mellitus; 1.27 for cerebrovascular disease; 1.17 for fall; 1.15 for chronic airway disease). The performances of the prediction models were area under the receiver operating curve of 0.73 and 0.75 for major osteoporotic and hip fractures. Conclusion: The study presented prediction models of major osteoporotic and hip fractures for osteopenia patients using simple clinical features.
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Fraturas do Quadril , Fraturas por Osteoporose , Humanos , Feminino , Idoso , Estudos de Coortes , Estudos Retrospectivos , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Fatores de Risco , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologiaRESUMO
BACKGROUND: The objective of this study is to identify predictors for recurrent appendicitis in patients with appendicitis previously treated nonoperatively. METHODS: This is a prospective cohort study of all adult patients with appendicitis treated at a tertiary care hospital. Patient demographics, radiographic information, management, and clinical outcomes were recorded. The primary outcome was recurrent appendicitis within 6 months after discharge from the index admission. Given the competing risk of interval appendectomy, a time-to-event competing-risk analysis was performed. RESULTS: Of the 699 patients presenting with appendicitis, 74 were treated nonoperatively (35 [47%] were women; median [IQR] age, 48 [33,64] years), and 21 patients (29%) had recurrent appendicitis. On univariate and multivariate analysis, presence of an appendicolith on imaging was the only factor associated with a higher risk of recurrent appendicitis (p = 0.02). CONCLUSIONS: The presence of appendicolith was associated with an increased risk of developing recurrent appendicitis within 6 months.
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Apendicite , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Apendicite/complicações , Apendicite/cirurgia , Estudos Prospectivos , Apendicectomia/métodos , Medição de Risco , Antibacterianos/uso terapêutico , Resultado do Tratamento , Estudos RetrospectivosRESUMO
CYP102A1 is a promiscuous bacterial cytochrome P450 (CYP or P450) known for its diverse substrates and comparable activity with human P450 enzymes. The development of CYP102A1 peroxygenase activity can contribute significantly to human drug development and drug metabolite production. Peroxygenase has recently emerged as an alternative to a dependency of P450 on NADPH-P450 reductase and NADPH cofactor and gives more opportunity for practical application. However, the H2O2 dependency also leads to challenges regarding its practical application, in which the excessive H2O2 concentration causes the activation of the peroxygenases. Therefore, we need the optimization of H2O2 production to minimize oxidative inactivation. In this study, we report the CYP102A1 peroxygenase-catalyzed atorvastatin hydroxylation reaction with an enzymatic H2O2 generation using glucose oxidase. Random mutagenesis at the CYP102A1 heme domain was used to generate mutant libraries with high throughput screening of highly active mutants, which can pair with the in situ H2O2 generation. The setup of the CYP102A1 peroxygenase reaction was also possible for other statin drugs and could be developed to produce drug metabolites. We also found a relationship between enzyme inactivation and product formation during the catalytic reaction, supported by enzymatic in situ H2O2 supply. It can be suggested that the low product formation is due to enzyme inactivation.
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Sistema Enzimático do Citocromo P-450 , Peróxido de Hidrogênio , Humanos , Sistema Enzimático do Citocromo P-450/metabolismo , Oxirredução , Catálise , Proteínas de Bactérias/químicaRESUMO
BACKGROUND: Recent studies raise concerns that arthroscopic meniscectomy (AM) for degenerative tear may be detrimental to the maintenance of the joint structure. This study was performed to examine the rate of total knee replacement (TKR) among patients with knee osteoarthritis (OA) who underwent AM for meniscal tears and compare this rate with those who did not. METHODS: A retrospective cohort study was conducted using the National Health Insurance Database of South Korea. Among knee OA patients aged 50-79, those who were treated with AM due to meniscal damage from 2007 to 2009 were selected as the AM group while those not treated with AM despite the presence of meniscal damage were selected as control group. Both were matched based on a propensity score and followed-up until the earliest occurrence of: TKR, death, or 10 years. Cox proportional hazards models were used to compare the outcome. RESULTS: A total of 36,974 patients were included in AM groups and non-AM group after 1:1 matching. TKR occurred in 9.62% and 7.64% in AM and non-AM groups with the average duration after meniscectomy of 5.88 ± 2.77 and 5.50 ± 2.94 years, respectively. After adjustment for baseline confounders, the TKR rate in the AM group was calculated to be 25% higher than that in the non-AM group (subdistribution hazard ratio, 1.25; 95% confidence interval, 1.16-1.34). The mortality rate was 5.20%, which did not significantly differ between groups. CONCLUSION: OA patients who underwent AM for the meniscal injury had higher incidence of TKR up to 10 years of follow-up than the non-operated group. The greater TKR utilization observed in patients undergoing AM merits caution when treating OA patients with meniscal injury.