Incidence of low back pain and potential risk factors among pharmacists: A population-based cohort study in Taiwan.

ABSTRACT: Low back pain (LBP) is one of the most common symptoms of work-related musculoskeletal disorders in pharmacists. This can impede the physical functions of the body and lead to incapacitation, resulting in significant social and economic burden. This study aimed to investigate the incidence and risk factors that correlate with LBP in Taiwanese pharmacists.A retrospective cohort study was conducted among all registered pharmacists aged 20 to 40 years using the National Health Insurance Research Database (2000-2013) in Taiwan. The LBP diagnosis was confirmed with one episode of hospitalization or at least three claimed outpatient visits for LBP. Data on workplace characteristics as well as comorbidities were also collected for the analyses. A Cox proportional hazard regression was used to estimate the risk factors for LBP.The incidence rate of LBP among pharmacists was 16.60% in this study. Older pharmacists (28.49%; P < .01) and those who worked at district hospitals (23.51%; P < .01) showed a higher proportion of LBP. Furthermore, after adjustment for selected potential confounding factors, female pharmacists [adjusted hazard ratio (aHR): 1.12, 95% confidence interval (95% CI): 1.01-1.24, P = .0354] and pharmacists with diabetes (aHR: 1.55; 95% CI: 1.20-2.01; P = .0008) and gout (aHR: 1.70; 95% CI: 1.37-2.09; P < .0001) had significantly higher risks of LBP.In conclusion, age was positively correlated with LBP, and the workplace was an important factor in the development of LBP in pharmacists. We suggest that pharmacists who work in district hospitals should pay more attention to the development of LBP.

Risk Factors in and Long-Term Survival of Patients with Post-Transplantation Diabetes Mellitus: A Retrospective Cohort Study.

Post-transplant diabetes mellitus (PTDM) is associated with infection, cardiovascular morbidity, and mortality. A retrospective cohort study involving patients who underwent renal transplantation in a transplantation center in Taiwan from January 2000 to December 2018 was conducted to investigate the incidence and risk factors of PTDM and long-term patient and graft survival rates. High age (45-65 vs. <45 years, adjusted odds ratio (aOR) = 2.90, 95% confidence interval (CI) = 1.64-5.13, p < 0.001), high body mass index (>27 vs. <24 kg/m2, aOR = 5.35, 95% CI = 2.75-10.42, p < 0.001), and deceased organ donor (cadaveric vs. living, aOR = 2.01, 95% CI = 1.03-3.93, p = 0.04) were the three most important risk factors for the development of PTDM. The cumulative survival rate of patients and allografts was higher in patients without PTDM than in those with PTDM (p = 0.007 and 0.041, respectively). Concurrent use of calcineurin inhibitors and mammalian target of rapamycin inhibitors (mTORis) decreased the risk of PTDM (tacrolimus vs. tacrolimus with mTORi, aOR = 0.28, 95% CI = 0.14-0.55, p < 0.001). Investigating PTDM risk factors before and modifying immunosuppressant regimens after transplantation may effectively prevent PTDM development.

Incidence and relative risk factors in posttransplant diabetes mellitus patients: a retrospective cohort study.

Background: Posttransplant diabetes mellitus (PTDM) has a long-term impact on kidney transplantation outcomes, such as graft and patient survival. The incidence and risk factors of PTDM are well studied, but long-term follow-up results remain unavailable. We examined the long-term incidence and relative risk factors of PTDM. Methods: A hospital information system database for kidney transplant recipients (KTRs) for a transplantation center between 1983 and 2018 was used to perform this retrospective cohort study. KTRs with DM diagnosis and continuous use of hypoglycemic agents for more than 3 months were defined as having PTDM. Demographics and comorbidities before transplantation were also collected. Kaplan-Meier analyses were used to determine the cumulative incidence and relative risk factors. Results: A total of 296 PTDM cases were confirmed (28.46%) in this study. An increased cumulative incidence associated with age was noted, which was significantly increased in those aged ≥40 years. Male sex, hypertension, hyperlipidemia before transplantation, cytomegalovirus (CMV) infection, and tacrolimus-based regimens were also risk factors. No significant correlation was found between the development of PTDM and the increase of human leukocyte antigen mismatches, the primary causes of end-stage renal disease, and acute rejection. Conclusions: PTDM incidence was high in this cohort study. Characteristics such as age ≥40 years, tacrolimus use, comorbidity of hypertension and hyperlipidemia before transplantation, and CMV infection were associated with a high risk of PTDM. Monitoring and adjusting preventable risk factors such as CMV infection might be useful to prevent PTDM.

Association between Potentially Inappropriate Medication Use and Chronic Diseases in the Elderly.

Long-term continuous exposure to potentially inappropriate medications (PIMs) can lead to adverse events in the elderly. However, the effects of long-term exposure of the elderly to PIM and the relationship between PIM and chronic diseases remain unclear. The objective of this study was to investigate the continuous use of PIMs in a community-dwelling elderly population. A cross-sectional population-based study was conducted using community pharmacy-filed dispensing records from the Hcare system. Twenty-three community pharmacies were sampled from 2013 to 2015 to obtain records of patients above 65 years-old with continuous prescriptions. PIM were identified according to the 2015 Beers Criteria. The prevalence of patients using PIM was highest in patients with co-morbid mental disorders (40.05%), followed by neurological system disorders (28.91%). Patients who were prescribed a PIM were more than three times as likely to have a mental disorder as those (odds ratio 3.16, 95% confidence interval: 3.06-3.28) with non-chronic diseases. The most prescribed PIM agents were central nervous system drugs (53.16%), and benzodiazepines (35.15%). Patients with mental disorders had the highest rate of long-term persistent PIM exposure, with benzodiazepines being the most frequently dispensed. Drug safety concerns should be closely monitored in elderly patients with the abovementioned conditions.

Hazards of Stroke in Renal Transplant Recipients and Patients With End-Stage Renal Disease.

BACKGROUND: Several comparison studies have suggested that kidney transplant (KT) could reduce stroke risk in patients with end-stage renal disease (ESRD). To avoid the selection criteria bias of using dialysis patients as control groups, we compared the risk of stroke between KT recipients and comparable propensity score-matched dialysis patients. METHODS: We used Taiwan's National Health Insurance Research Database to identify patients with newly diagnosed ESRD between 2000 and 2009. We separated them into 2 groups: a KT group and a non-KT dialysis-only group. To evaluate the stroke outcome, we compared each patient with KT to a patient on dialysis without KT using propensity score matching. RESULTS: In total, 2735 KT recipients and 10,940 propensity score-matched dialysis patients were identified. The incidence rates of overall stroke were 9.1 and 23.4 per 1000 person-years in KT recipients and non-KT dialysis patients. Compared with the propensity score-matched dialysis patients, the patients who received KT exhibited significantly lower overall stroke risk, hemorrhagic stroke, and ischemic stroke, the adjusted hazard ratios were 0.37 (95% CI, 0.31-0.45), 0.19 (95% CI, 0.12-0.29), and 0.46 (95% CI, 0.37-0.56), respectively (all P < .001). CONCLUSIONS: Through a propensity score-matched cohort, this study confirms that KT is associated with a reduced risk of stroke more than dialysis alone in patients with newly diagnosed ESRD.

Cross-sectional investigation of drug-related problems among adults in a medical center outpatient clinic: application of virtual medicine records in the cloud.

PURPOSE: To analyze and characterize data regarding the prevalence and types of outpatient drug-related problems (DRPs) found by clinical pharmacists after implementation of the Virtual Medicine Record in Cloud System (VMRCS). METHODS: A cross-sectional study regarding outpatient pharmaceutical care was conducted at a medical center in Taiwan. Patients aged >20 years old with multiple chronic diseases and polypharmacy were enrolled. In Stage I (1 October-31 December 2014), patients received pharmaceutical care according to prescription data accessed online in the VMRCS. In Stage II (1 June-31 August 2015), the VMRCS were pre-download and arranged to the institute's required format, facilitated DRP detection. Clinical pharmacists then reviewed and evaluated the prescription data through pre-downloaded VMRCS. Overall, 1539 and 1600 prescriptions were evaluated in these two stages, respectively. DRPs were recorded using the Pharmaceutical Care Network Europe (PCNE)-DRP. RESULTS: DRPs were found for 50.2% of patients in Stage I and 55.2% in Stage II (p < 0.05) and were most frequently encountered for "Drugs for the cardiovascular system" and caused by "Inappropriate duplication of therapeutic group or active ingredient." In terms of problems, incidence of "Unnecessary drug treatment" was highest. Duplicate medications were most frequently seen for "Drugs for acid-related disorders." The efficiency to identify DRPs was at least 2.4 times higher with pre-downloaded prescription data than with real-time online queries. CONCLUSIONS: With VMRCS, DRPs were more easily identified whether patients received medical care in the same hospital or not. DRPs could be efficiently prevented through the use of pre-downloaded patient prescription data. Copyright © 2016 John Wiley & Sons, Ltd.

WAY208466 inhibits glutamate release at hippocampal nerve terminals.

Evidence suggests that the glutamatergic system plays a crucial role in the pathophysiology and treatment of depression. This study investigates the effect of WAY208466, a 5-HT6 receptor agonist exhibiting an antidepressant effect, on glutamate release from rat hippocampal nerve terminals (synaptosomes). WAY208466 inhibited the Ca(2+)-dependent release of glutamate that was evoked by exposing the synaptosomes to the potassium channel blocker 4-aminopyridine, and the selective 5-HT6 receptor antagonist SB258585 blocked this phenomenon. The WAY208466-mediated inhibition of glutamate release was associated with a reduction of 4-aminopyridine-induced increase in the cytosolic free Ca(2+) concentration ([Ca(2+)]C) mediated via Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels. WAY208466 did not alter the resting synaptosomal membrane potential or 4-aminopyridine-mediated depolarization; thus, the inhibition of the Ca(2+) influx could not be attributed to the decrease in synaptosomal excitability caused by 5-HT6 receptor activation. Furthermore, the effect of WAY208466 on 4-aminopyridine-evoked glutamate release was prevented by a Gi/Go-protein inhibitor pertussis toxin, adenylate cyclase inhibitor SQ22536, and a protein kinase A inhibitor H89. These results suggest that WAY208466 acts at the 5-HT6 receptors present in the hippocampal nerve terminals to suppress the Gi/Go-protein-coupled adenylate cyclase/protein kinase A cascade, which subsequently reduces the Ca(2+) influx via N- and P/Q-type Ca(2+) channels to inhibit the evoked glutamate release. This finding implicated a potential therapeutic role of 5-HT6 receptor agonist in the treatment of depression and other neurological diseases associated with glutamate excitotoxicity.

Human cancer cells retain modest levels of enzymatically active matriptase only in extracellular milieu following induction of zymogen activation.

The type 2 transmembrane serine protease matriptase is broadly expressed in human carcinomas and hematological cancers. The proteolytic activity of matriptase is a potential target of drugs and imaging probes. We assessed the fate of active matriptase following the induction of matriptase zymogen activation. Exposing eight human carcinoma cells to pH 6.0 buffer induced robust matriptase zymogen activation followed by rapid inhibition of the nascent active matriptase by hepatocyte growth factor activator inhibitor (HAI)-1. Consequently, no enzymatically active matriptase was detected in these cells. Some active matriptase is, however, rapidly shed to the extracellular milieu by these carcinoma cells. The lack of cell-associated active matriptase and the shedding of active matriptase were also observed in two hematological cancer lines. Matriptase shedding is correlated closely with the induction of matriptase activation, suggesting that matriptase activation and shedding are kinetically coupled. The coupling allows a proportion of active matriptase to survive HAI-1 inhibition by rapid shedding from cell surface. Our study suggests that cellular free, active matriptase is scarce and might not be an effective target for in vivo imaging and drug development.

Blockade of reactive oxygen species and Akt activation is critical for anti-inflammation and growth inhibition of metformin in phosphatase and tensin homolog-deficient RAW264.7 cells.

CONTEXT: Metformin is widely used for treatment of type 2 diabetes and has a potential application on the treatment of inflammation and cancer. Phosphatase and tensin homolog (PTEN) plays a critical role in cancer cell growth and inflammation; however, precise mechanisms remain unclear. OBJECTIVE: We aimed to investigate the possible mechanisms of how PTEN regulates metformin against cell growth and inflammation. MATERIALS AND METHODS: We established PTEN knockdown in RAW264.7 murine macrophages (shPTEN cells) to detect inflammatory mediators using commercial kits, production of reactive oxygen species (ROS) by flow cytometry, cell growth by MTT assay and phosphorylated levels of signal molecules by western blot. RESULTS: The shPTEN cells had a significant large amount of inflammatory mediators, such as inducible nitric oxide synthase (iNOS)/nitric oxide (NO) and cyclooxygenase-2 (COX-2)/prostaglandin E(2) (PGE(2)); and also elevated the production of ROS and increased cell proliferation. These effects were accompanied with the activation of Akt and p38 mitogen-activated protein kinase (MAPK), and the inactivation of an AMP-activated protein kinase (AMPK) activator and extracellular signal-regulated kinase 1/2. Pretreatment with metformin not only blocked these inflammatory mediators, but also caused growth inhibition induced by significant apoptosis. Furthermore, inactivation of Akt, blockade of ROS generation and independence of activations of AMPK and MAPK by metformin were also observed. CONCLUSION: Macrophages with PTEN deficiency developed a continuous inflammatory microenvironment, which further aggravated tumor cell growth. Moreover, metformin affected PTEN-deficient cells dependent of inhibition of ROS production and Akt activation against enlarged inflammatory mediators and/or cell growth in shPTEN cells.

Leuconostoc mesenteroides growth in food products: prediction and sensitivity analysis by adaptive-network-based fuzzy inference systems.

BACKGROUND: An adaptive-network-based fuzzy inference system (ANFIS) was compared with an artificial neural network (ANN) in terms of accuracy in predicting the combined effects of temperature (10.5 to 24.5°C), pH level (5.5 to 7.5), sodium chloride level (0.25% to 6.25%) and sodium nitrite level (0 to 200 ppm) on the growth rate of Leuconostoc mesenteroides under aerobic and anaerobic conditions. METHODS: THE ANFIS AND ANN MODELS WERE COMPARED IN TERMS OF SIX STATISTICAL INDICES CALCULATED BY COMPARING THEIR PREDICTION RESULTS WITH ACTUAL DATA: mean absolute percentage error (MAPE), root mean square error (RMSE), standard error of prediction percentage (SEP), bias factor (Bf), accuracy factor (Af), and absolute fraction of variance (R (2)). Graphical plots were also used for model comparison. CONCLUSIONS: The learning-based systems obtained encouraging prediction results. Sensitivity analyses of the four environmental factors showed that temperature and, to a lesser extent, NaCl had the most influence on accuracy in predicting the growth rate of Leuconostoc mesenteroides under aerobic and anaerobic conditions. The observed effectiveness of ANFIS for modeling microbial kinetic parameters confirms its potential use as a supplemental tool in predictive mycology. Comparisons between growth rates predicted by ANFIS and actual experimental data also confirmed the high accuracy of the Gaussian membership function in ANFIS. Comparisons of the six statistical indices under both aerobic and anaerobic conditions also showed that the ANFIS model was better than all ANN models in predicting the four kinetic parameters. Therefore, the ANFIS model is a valuable tool for quickly predicting the growth rate of Leuconostoc mesenteroides under aerobic and anaerobic conditions.

Effectiveness of an integrated CPOE decision-supporting system with clinical pharmacist monitoring practice in preventing antibiotic dosing errors.

OBJECTIVE: Computer-prescriber order entry (CPOE) systems that lack clinical decision components actually increase errors and cause harm rather than the opposite. Recent studies have also demonstrated that dosing errors, typing errors, or miscommunication with other systems are the most common CPOE errors. Our objective was to develop an antibiotic dosing calculator and implement it in the CPOE system while integrating the role of the clinical pharmacist in the CPOE in order to minimize dosing errors in the prescription of antibiotics. METHODS: A database was prepared using dosage information for 13 renal function-related antibiotics. The dosages in the database ranged from the standard to the maximum dosage based on various creatinine clearance (CL(cr) levels. The antibiotic dosage monitoring system was developed to screen the entire inpatient database for inappropriate antibiotic dosage regimens and record the results as an Excel document. MAIN OUTCOME MEASURE: We tracked the frequency of calculator utilization by physicians, the acceptance rate of recommendations from the calculator and pharmacists, the inappropriate antibiotic dosage regimen prescriptions, and the antibiotic-related renal function deterioration. The relative risk (RR) with 95% confidence intervals (CI) was used to calculate the risk of inappropriate antibiotic dosage prescription, the deterioration in renal function when antibiotics were used. RESULTS: From 2005 to 2008, 38,647 antibiotic prescriptions were recorded in the CPOE system. The instances of inappropriate antibiotic dosage prescriptions were decreased by ~ 80% after the calculator was implemented (RR, 0.18 ­ 0.23; p < 0.001), and the incidence rates of renal function deterioration were lowered from 12.39% to 9.47%. The frequency of antibiotic calculator utilization by physicians (from 239 times/ year in 2005 to 3,480 times/year in 2008) and the acceptance rate of the calculator's dosage recommendations (from 68.2% in 2005 to 94.7% in 2008) both increased during the study period. The average acceptance rates of pharmacist recommendations by physicians were 97.65%. CONCLUSIONS: Integration of the CPOE decision-supporting system and the clinical pharmacist monitoring practice can help physicians provide appropriate antibiotic dosage regimens and decrease the incidence of dosing errors that could be decreased concerned patients with impaired renal function.

Pharmacoeconomic assessment of clinical pharmacist interventions for patients with moderate to severe asthma in outpatient clinics : experience in taiwan.

OBJECTIVE: To assess the economic and humanistic outcomes of clinical pharmacist interventions for patients with asthma and to assess the effect on patients' quality of life. STUDY DESIGN: A prospective cohort study was conducted at a medical centre in southern Taiwan. PATIENTS AND METHODS: Seventy patients with moderate to severe asthma were enrolled in the study from July 2003 to December 2003. Patients who were 17-53 years of age and were attending the outpatient clinic were referred to the pharmacist intervention programme. Patients were educated about their disease, pharmacotherapy, self-management and inhalation and peak flow meter techniques to use during the intervention period. A modified Asthma Quality-of-Life Questionnaire (AQLQ) was given to the patients at the first intervention (baseline) and 3 months later (intervention period) to assess quality of life. An asthma general knowledge questionnaire and an asthma diary chart were also used to assess patients' knowledge about asthma and the improvement in their symptoms. The cost effectiveness was evaluated based on the reduction in total costs/mean cost at each visit. RESULTS: Of the 70 asthmatic patients enrolled in the study; 55 completed the questionnaires at baseline and after the intervention period. Only 25 of 55 (45.5%) patients completed the asthma diary chart. After the pharmacist intervention period, the patients' quality of life, common knowledge about asthma, and peak expiratory flow rate (PEFR) were significantly improved as compared with baseline (p < 0.001). The frequency of use of beta(2)-agonists and corticosteroids were also reduced, although the reduction was not statistically significant. Total cost per patient at baseline was statistically different from that after the 3-month intervention period (New Taiwanese dollars [$NT] 2880 vs $NT1683, respectively; costings are costs during the study period). CONCLUSION: For patients with moderate to severe asthma, pharmacist intervention can be a cost-effective addition to the management of patients at an outpatient clinic by improving PEFR and patient quality of life, and saving medical resources.