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A fracture liaison services (FLSs) and its modified services reduce refractures and mortality and can be cost-effective. Limited studies have addressed whether urban-rural differences exist in vertebral fracture outcomes and management. Therefore, the aims of the study were to investigate any urban-rural differences in refracture, mortality, prescription pattern, and associated factors of vertebral fractures after receiving assistance from an FLSs.Baseline characteristics and osteoporosis medication prescription patterns of participants were collected. After 1-year follow-up, mortality, refracture rate, and osteoporosis medication switching and adherence were evaluated. Multivariate logistic regressions were performed to identify baseline correlates on one-year mortality.There was higher mortality rate in the rural group but no urban-rural difference in the 1-year refracture rate after implementation of FLSs and medication management services (MMSs). The types of osteoporosis medications prescribed for both groups were similar, but participants in the rural group were less likely to change their osteoporosis medications during the 1-year follow-up timeframe and with lower adherence rate. The likelihood of being older and having chronic kidney disease, osteoarthritis, and neurological disease was higher in the rural group.Our multicomponent services have similar effectiveness in osteoporosis treatment between urban and rural areas. The overall adherence rate was lower in the rural group with higher mortality but no difference in the refracture rate in one year.

Due to the huge gap in the care of patients with osteoporosis and fragility fractures, we aimed to explore the effectiveness of the osteoporosis liaison service (OLS) in osteoporosis care. We found that OLS can improve osteoporosis care, including increasing medication compliance, increasing calcium/vitamin D/protein intake, and reducing fall rate. A significant gap exists in the care of patients with osteoporosis and fragility fractures. This study aimed to evaluate 1-year outcomes of an osteoporosis liaison service (OLS) program that includes two independent components: medication management services (MMS) to improve medication adherence and fracture liaison services (FLS) for secondary prevention. Patients with new hip fracture or untreated vertebral fractures enrolled in the FLS program (n = 600), and those with osteoporosis medication management issues but not necessarily fragility fractures enrolled in the MMS program (n = 499) were included. To evaluate outcomes, care coordinators assessed baseline items adapted from the 13 Best Practices Framework (BPF) standards of the International Osteoporosis Foundation, with telephone follow-up every 4 months for 1 year. Mean age of this cohort was 76.2 ± 10.3 years, 78.8% were female. After 1-year participation in the program, all patients had received bone mineral density tests, and medication adherence for the entire cohort at 12 months was 91.9 ± 19.6%, with significant improvement in fall rates (23.4% reduction), exercise rates (16.8% increase), calcium intake (26.5% increase), vitamin D intake (26.4% increase), and adequate protein intake (17.3% increase) (all p < 0.05). After 1-year OLS program, the overall rates of mortality, incident fracture, and falls were 6.6%, 4.0%, and 24.3%, respectively. The OLS program is associated with improved osteoporosis care, including increased medication adherence, calcium/vitamin D and protein intake, and reduced fall rate.

Background/Purpose We examined the prevalence of probable common mental disorders (CMDs) in commercial low-dose computed tomography (LDCT) lung cancer screening consumers relative to the general population and to determine the correlates of probable CMDs among screening participants. Methods Commercial LDCT lung cancer screening consumers (N = 1323) were compared with a nationally representative sample from the Taiwan Social Change Survey (TSCS) (N = 2034). Respondents scoring ≥3 on the Chinese Health Questionnaire were classified as having a probable CMD. Logistic regression was used to investigate differences between the two groups and correlates of probable CMDs among LDCT lung cancer screening participants. Results The prevalence of probable CMDs was higher among LDCT lung cancer screening participants (25.47%) than among TSCS adults (21.56%). Compared with the TSCS sample, the screening participants had a higher probability of CMDs (OR = 1.40, 95% CI = 1.13–1.73), higher education levels (OR = 7.95, 95% CI = 6.00–10.53), and a history of drinking (OR = 11.85, 95% CI = 9.45–14.85) or betel-quid use (OR = 5.43, 95% CI = 3.98–7.42) but were less likely to smoke (OR = 0.52, 95% CI = 0.40–0.68). Among the screening participants, being female (OR = 1.37, 95% CI = 1.02–1.84) and a current smoker (OR = 1.74, 1.19–2.54) and living near ≥2 smoking family members (OR = 2.30, 95% CI 1.57–3.38) were associated with an increased likelihood of having CMDs. Conclusion Commercial LDCT lung cancer screening users may have a positive association with probable CMDs compared to the general population. Screening programs should consider including criteria and providing psychoeducation to improve the physical and mental outcomes of participants. Clinical trial registration Purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) do not require registration.

Osteoporosis medication in fragility fracture patients is associated with better outcomes. However, limited studies have investigated whether fracture types affect outcomes among patients undergoing treatment. We performed a secondary data analysis on participants from a fracture liaison service and an osteoporosis medication management service. Participants (n = 974) were regrouped into hip fracture (HF), vertebral fracture (VF), HF + VF, and NO HF/VF groups at baseline. Bivariate and multivariate logistic regressions were performed to identify baseline correlates on one-year mortality, incident refractures, and falls. Baseline characteristics were different among fracture groups. The HF group was oldest, with the lowest body mass index (BMI), lowest FRAX® T-score and had the highest 10-year fracture risk. After intervention, the HF group still had the highest mortality, but the HF + VF group had the highest refracture and incident fall rates. In the multivariate regression analysis, prevalent HF and VF, lower BMI and albumin level, and having chronic kidney disease or cancer were associated with higher mortality rates. HF + VF patients had the highest refracture risk. Prevalent HF and VF, older age and higher BMI, and having cancer or osteoarthritis were associated with a greater fall risk. HF and VF are associated with adverse outcomes, even under an optimal fracture care.

Background: PIM-Taiwan criteria were first established in 2010 for potentially inappropriate medications (PIMs). Currently, updating of PIM criteria is mandatory because of newly established evidence and newly developed medications. This study aims to evaluate the prevalence of PIM based on country-specific PIM criteria and factors associated with PIM use by applying 2010 version and newly updating PIM-Taiwan criteria in a cohort with polypharmacy. Methods: The baseline data of Medication Safety Review Clinic Taiwan (MSRC–Taiwan) study were used to investigate the prevalence of PIMs. Older patients (aged ⩾65 years) who were either having polypharmacy or visited ⩾3 different physicians were enrolled between August and October 2007. Bivariate analysis and multivariate logistic regressions were used to evaluate the factors associated with PIM use. Results: The prevalence of having at least one PIM was 46.1% for 2010 version and increased to 74.6% for 2018 version. The average number of PIMs generally to be avoided per patient also increased for 2018 version (0.2 versus 1.2, p < 0.0001). In contrast, the average number of PIMs considering chronic conditions per patient decreased (0.6 versus 0.3, p < 0.001). The associated chronic conditions of PIM users were distinct between 2010 and 2018 version. The major leading PIMs were benzodiazepines (BZDs) in both versions of criteria. Conclusions: As there were significant differences in medication lists between PIM-Taiwan version 2010 and 2018, the prevalence of PIM and factors associated with PIM users varied accordingly. Physicians should pay special attention before prescribing BZDs which keep being the major leading PIM.

Potentially inappropriate medication (PIM) was associated with adverse clinical outcomes and higher healthcare resource utilization among older patients. In order to investigate the prevalence of PIM use based on three different sets of criteria and their associated factors among older patients in the emergency department (ED) in Taiwan. The National Health Insurance Research Database was used for this cross-sectional study. Older patients who visited the ED at least once in 2009 were enrolled. PIMs were identified based on the Beers Criteria, PIM-Taiwan criteria, and PRISCUS criteria. Average patient age was 76.7 ± 7.4 years and patients visited the ED 1.8 ± 2.1 times in 2009. The prevalence and frequency of being prescribed at least one PIM at each visit were high according to all three sets of criteria. Performance of the PIM-Taiwan criteria was only inferior to that of the Beers Criteria. The most important factor associated with PIM was the number of medications prescribed in the ED, and PIM use was associated with higher annual health resource utilization in the ED. PIM use was a significant issue and was associated with higher annual emergency care resource utilization in the ED.

The absorption, action, and metabolism characteristics of drugs change in older adults due to factors including the normal process of aging and the impacts of disease on organ functions. Changes in the profile and proportions of drug use among older adults increase with increases in the severity of functional decline and the prevalence of chronic diseases. Drugs that are classified as "potentially inappropriate medications" (PIMs) carry a higher risk of causing adverse reactions in older adults, provide uncertain therapeutic benefits, or may be substituted by alternative drugs that are generally safer to use. Researchers have developed criteria for PIMs in geriatric medicine that are applicable to clinical practice and research. This article introduces the development and application of the PIM-Taiwan criteria to help nurses better understand the current knowledge related to medication use among older adults and the results of related research in Taiwan.臺灣潛在性不適當用藥評估工具的發展與應用.老年人因器官老化或疾病影響，對於藥物的吸收、作用與代謝也隨之改變。且隨著年齡增加身體功能下降與慢性病盛行比例增加，老年人使用藥物的機會與比例也隨之增加。特定一些藥物稱為「潛在性不適當藥物」，它們對於老年人較容易產生不良反應，且治療效果不明確或有其他較安全的替代藥物。隨著老年醫學的發展，各國陸續發展「潛在性不適當藥物」準則給予臨床人員參考、進行研究等運用。本篇文章主要介紹臺灣版準則的發展與應用，期能讓護理師了解老年用藥的相關知識與臺灣本土研究結果。.

Background Exercise, nutrition, and psychological interventions may all have positive impacts on frailty and sarcopenia. However, it is not known whether an integrated care programme with all three components can be beneficial and the intensity of such programme is also not certain. In this study, we aim to determine the effectiveness of two levels of integrated care on frailty and sarcopenia. Methods A randomized control trial was conducted at two community hospitals in Taiwan. Older adults (65–79 years of age, N = 289) who scored ≥1 on the Cardiovascular Health Study Phenotypic Classification of Frailty (CHS_PCF) were enrolled in the trial. Low-level care (LLC) participants received a 2 h education course on frailty, sarcopenia, coping strategy, nutrition, and demonstration of study exercise programme. Educational multimedia material was distributed as reference for home practice with bi-monthly telephone follow-ups on adherences. High-level care (HLC) participants, in addition to LLC instructions, received six sessions of on-site problem solving therapy and 48 exercise sessions within 6 months. Brief nutrition consultation was also provided during the exercise sessions. Primary outcome was improvement of the CHS_PCF by at least one category (from pre-frail to robust, or from frail to pre-frail or robust) from baseline. Secondary outcomes included changes of individual frailty, and sarcopenia indicators. Assessments were done at 3, 6, and 12 months by trained research assistants blinded to randomization status. Intention-to-treat analysis was applied. Results Mean age was 71.6 ± 4.3 years, with 53% females. For the entire cohort, improvement of primary outcome was 35% at 3 months, increased to 40% at 6 months, and remained stable at 39% at 12 months. Improvement rates were similar in both groups. Compared with the LLC group, HLC participants had greater improvements in the following indices: energy expenditure of walking, 5 m walking time, dominant hand grip strength, timed-up-and-go-test, and one-leg-stand time — mainly at 6 and 12 month assessments. Conclusions The 6 month integrated care improved frailty and sarcopenia status among community-dwelling elders, with high-intensity training yielding greater improvements. Low-level care could be promoted as a basic intervention, while HLC could be reserved for those at high risk and with high motivation.

Background Anticoagulants are used to reduce the risk of stroke in patients with atrial fibrillation (Af) and chronic kidney disease (CKD). Warfarin is one of the commonly used anticoagulants; however, its effect on renal function remains unclear. Methods In a retrospective cohort study (January 2001 - July 2013), we surveyed data charts from 2,450 patients with stage 3 - 5 CKD, and enrolled 159 patients with Af. In total, 104 patients had a CHADS2 score of >= 2 (congestive heart failure, hypertension, >= 75 years old, diabetes, 1 point; prior stroke or transient ischemic attack or thromboembolism, 2 points). These patients were categorized into groups A and B based on warfarin treatment. Group A included 73 patients and was not undergoing warfarin treatment and group B included 31 patients undergoing warfarin treatment. The baseline demographic and biochemical data as well as changes in estimated glomerular filtration rate (eGFR) after 6, 12, and 18 months of warfarin treatment were analyzed. We also studied censored patient survival over 12 years using Kaplan-Meier model. Results The mean international normalization ratio (INR) of warfarin treatment in group B was 1.92 ± 1.04. Moreover, group B showed a significant increase in eGFR. The maximum improvement was at 6 months (mean eGFR increased from 25.97 to 31.12 mL/min; p = 0.01) and lasted for up to 18 months (eGFR 28.65 mL/min). Despite higher initial CHADS2 scores, group B showed a superior survival rate compared with group A (p = 0.02). Conclusion Lower doses of warfarin may protect against renal dysfunction and could be beneficial for treatment of stage 3 - 5 CKD with Af.

Background Explicit criteria for potentially inappropriate medications (PIMs) developed from other regions were often difficult to apply to a specific territory without significant modifications. Purpose To describe a process of developing a country-specific explicit PIM criteria from quality review of several published PIM criteria, followed by consensus among regional experts in Taiwan. Methods After a review of the literature, we selected seven sets of published PIM criteria. Medications/medication classes listed in at least three of the seven sets of criteria were selected as preliminary core PIMs. We asked a group of 21 experts from various specialties to rate how appropriate they found inclusion of each medication/medication class in final PIM criteria after two rounds of modified Delphi methods. Results Table 1 of the instrument included 24 medication/medication classes to be generally avoided in older adults irrespective of comorbidities, and Table 2 included 12 chronic conditions with six medication/medication classes that patients with these conditions should avoid. The Taiwan criteria contained only half the number of statements that were included in the Beers criteria (36 vs 68 statements) but detected nearly 70–75% as many PIMs in older patients with polypharmacy in a secondary data analysis. Features included straightforward statement arrangements, suggestions of alternatives, and clear definitions of long-acting benzodiazepine and anticholinergic drugs for Table 1 PIMs. Conclusion A user-friendly instrument was developed to detect PIMs for Taiwanese older adults. Further prospective studies are needed to validate its use in clinical and research settings. Copyright © 2012 John Wiley & Sons, Ltd. key words—potentially inappropriate medications; explicit criteria; aged; pharmacoepidemiology

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Many different criteria have been developed to detect potentially inappropriate medications (PIMs), with wide variations in prevalence estimates and inconsistent associations with health outcomes. • Without head-to-head comparisons, it is difficult to know whether some PIM criteria systematically detect more or fewer PIMs than others in the same cohorts. WHAT THIS STUDY ADDS • Six sets of PIM criteria were applied to a single cohort, with PIM prevalence ranging from 24 to 73%. • Criteria with a higher number of statements and a higher percentage of local market/institution drug availability tended to detect more PIMs. • Caution should be exercised in applying PIM criteria developed in other regions when medication availability in the local market is limited. AIM Our aim was to compare the practicability of six different potentially inappropriate medication (PIM) criteria in geriatric outpatients with polypharmacy. METHODS We analysed baseline data from the Medication Safety Review Clinic in Taiwanese Elders (MSRC-Taiwan) study. The prevalence and correlates of PIMs were determined on the basis of criteria developed in the USA, Canada, France, Norway, Ireland and Thailand. The percentage of PIMs considered as drug-related problems and the problem-solving rate are reported. RESULTS In the 193 participants, the prevalence of PIM varied from 24 to 73%. Application of the criteria revealed that a high number of chronic medications was a common risk factor for having at least one PIM. Of the 1713 medications reviewed, 5.6–14.8% were considered PIMs. Only 30–40% of the identified PIMs were reported as drug-related problems by the MSRC team experts. Criteria with a higher number of statements and a higher percentage of local market/institution drug availability tended to detect more PIMs. CONCLUSIONS The prevalence of PIM varied significantly when different criteria were applied. Caution should be exercised in applying PIM criteria developed in other regions when medication availability in the local market is limited.

Several sets of explicit criteria for potentially inappropriate medications (PIMs) have been developed by expert consensus. The purpose of this review is to summarize and compare existing criteria to enable more informed choices about their use. After a systematic literature search was conducted, seven examples of criteria published between 1991 and 2009 were included in the review and their individual characteristics are presented. Common medications listed in the majority of these criteria are also summarized. PIMs listed regardless of co-morbidities in all seven criteria sets were long-acting benzodiazepines and tricyclic antidepressants. PIMs regardless of co-morbidities were most similar among the Beers, Rancourt and Winit-Watjana criteria. Several drug-disease interactions such as benzodiazepines and falls were cited in most criteria. With respect to drug-drug interactions, most criteria agreed that concomitant use of warfarin and NSAIDs should be avoided. The prevalence of PIMs varied with patient population, availability of medications in local markets, the specialties of the prescribing physicians and the assessment instruments used. The associations between PIMs use and health outcomes were largely inconclusive because of limited data. Further research is necessary to validate these published criteria in terms of reducing the incidence of adverse drug reactions and improving health outcomes among older adults. Incorporation of these criteria into computer-assisted order entry systems would increase their utilization in daily practice.

The Taiwanese FRAXUsing previous data from Taiwan and literature, we determined cost-effectiveness thresholds for prevention of osteoporotic fractures by alendronate with a Markov model, as well as using two other translational approaches. Sensitivity analysis was applied using different alendronate prices. A clinical sample was used to test these Taiwan-specific thresholds by determining the percentages of high-risk patients who would be qualified for current National Health Insurance reimbursement.With the Markov model, the intervention threshold for hip fracture was 7% for women and 6% for men; for major osteoporotic fracture, it was 15% for women and 12.5% for men. Both translational approach models were cost effective only for certain age groups. However, if branded alendronate was reimbursed at 60% of the current price, they became cost effective in almost all age groups. This clinical screening study showed that the National Health Insurance Administration model identified the highest proportion (44%) of patients qualified for National Health Insurance reimbursements, followed by the Markov model (30%), and the United States model (22%).Three FRAX

Emphysematous cystitis is a relatively rare infectious condition of the urinary bladder. The mortality rate is high if the diagnosis is delayed or if the treatment is inadequate. We present an uncommon case of emphysematous cystitis and highlight the risk factors for this disease. An 81-year-old man with a past medical history of type 2 diabetes and a central pontine infarction presented to the Emergency Department due to gross hematuria. Computed tomography (CT) and plain radiography revealed localized gas within the bladder that was compatible with the diagnosis of emphysematous cystitis. A Foley catheter was inserted. Urine culture grew Klebsiella pneumoniae; 2 g cefotaxime daily was initiated. Subsequent plain radiography and CT scan showed regression of intraluminal gas. We recommend CT for the definitive diagnosis of emphysematous cystitis. Adequate antibiotic therapy, strict blood glucose control, adequate drainage of urine, and early goal-directed therapy for suspected sepsis are suggested to prevent the complications of emphysematous cystitis.

Background Endotoxemia is exaggerated and contributes to systemic inflammation and atherosclerosis in patients requiring continuous ambulatory peritoneal dialysis (CAPD). The risk of mortality is substantially increased in patients requiring CAPD for >2 years. However, little is known about the effects of long-term CAPD on circulating endotoxin and cytokine levels. Therefore, the present study evaluated the associations between plasma endotoxin levels, cytokine levels, and clinical parameters with the effects of a short-dwell exchange on endotoxemia and cytokine levels in patients on long-term CAPD. Methods A total of 26 patients were enrolled and divided into two groups (short-term or long-term CAPD) according to the 2-year duration of CAPD. Plasma endotoxin and cytokine levels were measured before and after a short-dwell exchange (4-h dwell) during a peritoneal equilibration test (a standardized method to evaluate the solute transport function of peritoneal membrane). These data were analyzed to determine the relationship of circulating endotoxemia, cytokines and clinical characteristics between the two groups. Results Plasma endotoxin and monocyte chemotactic protein-1 (MCP-1) levels were significantly elevated in the long-term group. PD duration was significantly correlated with plasma endotoxin (r = 0.479, P = 0.016) and MCP-1 (r = 0.486, P = 0.012). PD duration was also independently associated with plasma MCP-1 levels in multivariate regression. Plasma MCP-1 levels tended to decrease (13.3% reduction, P = 0.077) though endotoxin levels did not decrease in the long-term PD group after the 4-h short-dwell exchange. Conclusion Long-term PD may result in exaggerated endotoxemia and elevated plasma MCP-1 levels. The duration of PD was significantly correlated with circulating endotoxin and MCP-1 levels, and was an independent predictor of plasma MCP-1 levels. Short-dwell exchange seemed to have favorable effects on circulating MCP-1 levels in patients on long-term PD.

OBJECTIVES: Taiwanese National Health Insurance (TNHI) provides home healthcare services to patients with skilled nursing needs who were homebound or lived in nursing homes. Studies on potentially inappropriate medications (PIMs) for older home healthcare service recipients (HHSRs) are growing, but comparisons among newer criteria of PIMs have not been applied. The aim of this study was to explore the prevalence and correlates of PIMs based on three different instruments published after 2010 among older HHSRs. MATERIALS AND METHODS: We performed cross-sectional analysis of the TNHI Research Database. A total of 25,187 HHSRs aged more than 65 years in 2009 were included. Medication lists independent of chronic conditions from the 2012 Beers criteria, PIM-Taiwan criteria, and the PRISCUS (Latin for "old and venerable") criteria were used. Analysis was performed separately at patient and clinic-visit level. T-tests, chi-square analysis, and multivariate logistic regressions were used where appropriate. RESULTS: The prevalence of having at least one PIM at patient and clinic-visit level was highest with the Beers (82.67%, 36.14% respectively), followed by the PRISCUS (68.49%, 25.13%) and PIM-Taiwan (63.04%, 19.21%) criteria. At patient level, polypharmacy (odds ratio (OR) 2.53 to 4.90), higher number of clinic (OR 1.15 to 1.41), hospital (OR 1.24 to 1.64), and physician (OR 1.15 to 1.41) visits were associated with PIM use for all 3 sets of criteria. At clinic-visit level, internist/family physicians (OR 1.26 to 1.72) and neurologists/psychiatrists (OR 1.73 to 5.87) were more likely to prescribe PIMs than others. Psychotropic drugs and first generation antihistamines accounted for most of the top ten PIMs. CONCLUSION: The prevalence of PIMs was high among older Taiwanese HHSRs. Polypharmacy and certain medical specialties were associated with a higher likelihood of PIM prescriptions. Provider education and medication review and reconciliation should be considered.

Purpose In our previous study, type 2 diabetic chronic kidney disease (CKD) patients with glomerular filtration rates of 9 days, Group B) groups. The differences in the continuous and categorical variables of the two groups were assessed separately. The mean glucose levels and their variability (using the standard deviation and the coefficient of standard deviation) were compared at the fasting, midday pre-meal, evening pre-meal, and evening post-meal time points during hospitalization. We have organized the manuscript in a manner compliant with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement. Results Acute kidney injury occurred within the two groups (p = 0.007 and p = 0.001, respectively). The early-morning blood glucose levels (149.7±44.0 mg/dL) and average blood glucose levels (185.6±52.0 mg/dL) were better in Group A (p = 0.01, p = 0.02). Group A patients also had lower glucose variability than Group B at the different time points (p

The effects of calcium, calmodulin, protein kinase C (PKC) and protein tyrosine kinase (PTK) modulators were examined on the volume-activated taurine efflux in the erythroleukemia cell line K562. Exposure to hypoosmotic solution significantly increased taurine efflux and intracellular calcium concentration ([Ca2+]i). The Ca2+ channel blockers La3+ (1 mM), verapamil (200 microM) and nifedipine (100 microM) inhibited the hypoosmotically-induced [Ca2+]i increase by more than 90%, while the volume-activated taurine efflux was inhibited by 61.3 +/- 9.5, 74.1 +/- 9.3 and 38.0 +/- 1.5%, respectively. Furthermore, the calmodulin inhibitors W7 (50 microM) and trifluoperazine (10 microM) and the Ca2+/calmodulin-dependent protein kinase II inhibitor KN-62 (2 microM) significantly blocked the volume-activated taurine efflux by 93.4 +/- 2.7, 77.9 +/- 3.5 and 61.3 +/- 15.8%, respectively. In contrast, the PKC inhibitor staurosporine (200 nM) or the PKC activator phorbol 12-myristate 13-acetate (100 nM) did not have significant effects on the volume-activated taurine efflux. However, pretreatment with PTK inhibitors genistein, tyrphostin A25, and tyrphostin A47 blocked the volume-activated taurine efflux. These results suggest that the volume-activated taurine efflux in K562 cells may not directly involve Ca2+, but may require the presence of calmodulin and/or PTK.

Purpose : Crosstalk between Aurora-A kinase and p53 has been proposed. While the genetic amplification of Aurora-A has been observed in many human cancers, how p53 is regulated by Aurora-A remains ambiguous. In this study, Aurora-A-mediated phosphorylation of p53 was analyzed by mass spectrometry in order to identify a new phosphorylation site. Subsequently, the functional consequences of such phosphorylation were examined. Experimental design : In vitro phosphorylation of p53 by Aurora-A was performed and the phosphorylated protein was then digested with trypsin and enriched for phosphopeptides by immobilized metal affinity chromatography. Subsequently, a combination of β-elimination and Michael addition was applied to the phosphopeptides in order to facilitate the identification of phosphorylation sites by MS. The functional consequences of the novel phosphorylation of p53 on the protein–protein interactions, protein stability and transactivation activity were then examined using co-immunoprecipitation, Western blotting and reporter assays. Results : Ser-106 of p53 was identified as a novel site phosphorylated by Aurora-A. A serine-to-alanine mutation at this site was found to attenuate Aurora-A-mediated phosphorylation in vitro . In addition, phosphate-sensitive Phos-tag SDS-PAGE was used to confirm that the Ser-106 of p53 is in vivo phosphorylated by Aurora-A. Finally, co-immunoprecipitation studies suggested that Ser-106 phosphorylation of p53 decreases its interaction with MDM2 and prolongs the half-life of p53. Conclusions : The inhibition of the interaction between p53 and MDM2 by a novel Aurora-A-mediated p53 phosphorylation was identified in this study and this provides important information for further investigations into the interaction between p53 and Aurora-A in terms of cancer biology.

Nephrotic syndrome complicated by necrotizing fasciitis is rare. Necrotizing fasciitis is a skin and soft tissue infection with a rapid progression and difficult diagnosis. Moreover, the early presentation of necrotizing fasciitis is similar to that of cellulitis. Serratia marcescens is a rare pathogenic cause of necrotizing fasciitis, even in skin and soft tissue infection. We present a patient with nephrotic syndrome complicated by necrotizing fasciitis caused by Serratia marcescens. A 49-year-old Chinese woman presented with minimal change disease and nephritic syndrome. She was admitted for pain in her right leg, for which she received cefazolin and clindamycin. However, 3 days later, a sanguineous bulla developed over her left calf, and she developed septic shock. After an emergency fasciotomy and broad-spectrum antibiotic administration, this patient died 12 h after fasciotomy. The blood culture and deep tissue culture collected during surgery both yielded Serratia marcescens. This unusual case reminds physicians that gramnegative bacilli can be pathogenic in soft tissue, especially in immunocompromised patients.

Explicit criteria for potentially inappropriate medications (PIMs) developed from other regions were often difficult to apply to a specific territory without significant modifications.To describe a process of developing a country-specific explicit PIM criteria from quality review of several published PIM criteria, followed by consensus among regional experts in Taiwan.After a review of the literature, we selected seven sets of published PIM criteria. Medications/medication classes listed in at least three of the seven sets of criteria were selected as preliminary core PIMs. We asked a group of 21 experts from various specialties to rate how appropriate they found inclusion of each medication/medication class in final PIM criteria after two rounds of modified Delphi methods.Table 1 of the instrument included 24 medication/medication classes to be generally avoided in older adults irrespective of co-morbidities, and Table 2 included 12 chronic conditions with six medication/medication classes that patients with these conditions should avoid. The Taiwan criteria contained only half the number of statements that were included in the Beers criteria (36 vs 68 statements) but detected nearly 70-75% as many PIMs in older patients with polypharmacy in a secondary data analysis. Features included straightforward statement arrangements, suggestions of alternatives, and clear definitions of long-acting benzodiazepine and anticholinergic drugs for Table 1 PIMs.A user-friendly instrument was developed to detect PIMs for Taiwanese older adults. Further prospective studies are needed to validate its use in clinical and research settings.

Chia-Chu Chang,1,2 Hung-Hsiang Liou,1 Chia-Lin Wu,1 Chirn-Bin Chang,1,2 Yu-Jun Chang,3 Ping-Fang Chiu,1,2 Ching-Hui Huang41Division of Nephrology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 2School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 3Epidemiology and Biostatistics Center, 4Division of Cardiology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, TaiwanBackground: The purpose of this study was to examine whether long-term use of anticoagulants in elderly patients with atrial fibrillation (AF) and chronic kidney disease (CKD) influences renal function.Methods: In this retrospective observational study, we reviewed the records of 2023 patients who attended our institution for treatment of CKD between January 2001 and September 2012. Inclusion criteria were having been under review for three months or more, age older than 60 years, permanent AF, a CHADS2 score > 2, and National Kidney Foundation Kidney Disease Outcomes Quality Initiative CKD stage 3–5. Sixty-one patients fulfilled these criteria, and were divided into those receiving antiplatelet anticoagulation (group A) and those receiving warfarin (group B). The results of laboratory investigations and estimated glomerular filtration rate (GFR) were recorded at months 3, 6, 12, and 18 from treatment initiation. We also recorded the occurrence of serious cardiovascular and neurological events, significant bleeding, and survival beyond 12 years.Results: Of the 61 patients enrolled, 35 were in group A and 26 were in group B. The mean international normalized ratio (INR) was 1.95 ± 1.01 (goal < 3.0). After adjustment for potential confounding variables, we found that patients in group B had a higher estimated GFR (6.06 ± 2.36 mL per minute, P = 0.01). Over a 12-year observation period, group B patients had significantly (P = 0.013) better survival than group A, with an adjusted hazard ratio for mortality of 0.318 (P = 0.022).Conclusion: Warfarin therapy may delay deterioration in renal function and improve survival of elderly patients with CKD and AF.Keywords: aged, atrial fibrillation, chronic kidney disease, vitamin K antagonists, warfarin

Background/purpose: The Taiwanese FRAX® calculator was launched in 2010. However, cost-effectiveness thresholds for the prescription of antiosteoporosis medications were not established. This study aims to establish and evaluate FRAX®-based probability thresholds in Taiwan. Methods: Using previous data from Taiwan and literature, we determined cost-effectiveness thresholds for prevention of osteoporotic fractures by alendronate with a Markov model, as well as using two other translational approaches. Sensitivity analysis was applied using different alendronate prices. A clinical sample was used to test these Taiwan-specific thresholds by determining the percentages of high-risk patients who would be qualified for current National Health Insurance reimbursement. Results: With the Markov model, the intervention threshold for hip fracture was 7% for women and 6% for men; for major osteoporotic fracture, it was 15% for women and 12.5% for men. Both translational approach models were cost effective only for certain age groups. However, if branded alendronate was reimbursed at 60% of the current price, they became cost effective in almost all age groups. This clinical screening study showed that the National Health Insurance Administration model identified the highest proportion (44%) of patients qualified for National Health Insurance reimbursements, followed by the Markov model (30%), and the United States model (22%). Conclusion: Three FRAX®-based models of alendronate use were established in Taiwan to help optimize treatment strategies. The government is encouraged to incorporate FRAX®-based approaches into the reimbursement policy for antiosteoporosis medicines.

Background Glyphosate is an herbicide considered to be of low toxicity to humans because its effects are specific to plants. However, fatal reactions to glyphosate have been reported after the ingestion of large amounts. Pulmonary edema, shock, and arrhythmia were the reported causes of mortality. Case presentation We present the case of a 57-year-old woman who was admitted to the emergency department unconsciousness after ingestion of glyphosate surfactant in a suicide attempt. Metabolic acidosis, refractory respiratory failure, and shock developed during hospitalization. Despite aggressive supportive care, the patient died in the hospital. Conclusion The toxicokinetics of glyphosate surfactant is complicated. Respiratory failure, metabolic acidosis, tachycardia, elevated creatinine, and hyperkalemia are poor prognostic factors if presented. Physicians should consider using hemodialysis early to improve the outcome of patients with glyphosate surfactant intoxication.