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Zhan-Miao Yi,1–3 Cheng Wen,1,2 Ting Cai,4 Lu Xu,4 Xu-Li Zhong,5 Si-Yan Zhan,4,6 Suo-Di Zhai1,3 1Department of Pharmacy, Peking University Third Hospital, Beijing, China; 2Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Science, Peking University Health Science Center, Beijing, China; 3Institute for Drug Evaluation, Peking University Health Science Center, Beijing, China; 4Department of Epidemiology and Bio-statistics, School of Public Health, Peking University Health Science Center, Beijing, China; 5Department of Pharmacy, Children’s Hospital Affiliated to Capital Institute of Pediatrics, Beijing, China; 6Center for Clinical Epidemiology, Peking University Third Hospital, Beijing, China Objective: To evaluate the efficacy, safety and economics of levetiracetam (LEV) for epilepsy. Materials and methods: PubMed, Scopus, the Cochrane Library, OpenGrey.eu and ClinicalTrials.gov were searched for systematic reviews (SRs), meta-analyses, randomized controlled trials (RCTs), observational studies, case reports and economic studies published from January 2007 to April 2018. We used a bubble plot to graphically display information of included studies and conducted meta-analyses to quantitatively synthesize the evidence. Results: A total of 14,803 records were obtained. We included 30 SRs/meta-analyses, 34 RCTs, 18 observational studies, 58 case reports and 2 economic studies after the screening process. The included SRs enrolled patients with pediatric epilepsy, epilepsy in pregnancy, focal epilepsy, generalized epilepsy and refractory focal epilepsy. Meta-analysis of the included RCTs indicated that LEV was as effective as carbamazepine (CBZ; treatment for 6 months: 58.9% vs 64.8%, OR=0.76, 95% CI: 0.50–1.16; 12 months: 54.9% vs 55.5%, OR=1.24, 95% CI: 0.79–1.93), oxcarbazepine (57.7% vs 59.8%, OR=1.34, 95% CI: 0.34–5.23), phenobarbital (50.0% vs 50.9%, OR=1.20, 95% CI: 0.51–2.82) and lamotrigine (LTG; 61.5% vs 57.7%, OR=1.22, 95% CI: 0.90–1.66). SRs and observational studies indicated a low malformation rate and intrauterine death rate for pregnant women, as well as low risk of cognitive side effects. But psychiatric and behavioral side effects could not be ruled out. LEV decreased discontinuation due to adverse events compared with CBZ (OR=0.52, 95% CI: 0.41–0.65), while no difference was found when LEV was compared with placebo and LTG. Two cost-effectiveness evaluations for refractory epilepsy with decision-tree model showed US$ 76.18 per seizure-free day gained in Canada and US$ 44 per seizure-free day gained in Korea. Conclusion: LEV is as effective as CBZ, oxcarbazepine, phenobarbital and LTG and has an advantage for pregnant women and in cognitive functions. Limited evidence supports its cost-effectiveness. Registered number: PROSPERO (No CRD 42017069367). Keywords: seizure freedom, responder rate, quality of life, malformations, neurological development, psychiatric side effects, cost-effectiveness

Zhan-Miao Yi,1–3 Ting-Ting Qiu,1,4 Yuan Zhang,5 Na Liu,6 Suo-Di Zhai1,3 1Department of Pharmacy, Peking University Third Hospital, 2Department of Pharmacy Administration and Clinical Pharmacy, Peking University School of Pharmaceutical Science, 3Institute for Drug Evaluation, Peking University Health Science Center, Beijing, China; 4Public Health Department, Aix-Marseille University, Marseille, France; 5Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; 6Department of Neurology, Peking University Third Hospital, Beijing, China Aims: To review the evidence for efficacy, safety, and cost-effectiveness of levodopa/carbidopa/entacapone (LCE) compared with levodopa/dopa-decarboxyiase inhibitor (DDCI) for Parkinson’s disease (PD).Methods: PubMed, Embase, the Cochrane Library, and Chinese databases WangFang Data, Chinese Sci-tech Journals Database and China National Knowledge Infrastructure, as well as ClinicalTrials.gov, were searched for randomized controlled trials with “levodopa/carbidopa/entacapone” as keywords. The search period was from inception to August 2017. We conducted meta-analyses to synthesize the evidence quantitatively.Results: A total of 5,693 records were obtained. We included seven randomized controlled trials and one cost-effectiveness study after the screening process. Compared with levodopa–DDCI, LCE improved patient Unified Parkinson’s Disease Rating Scale (UPDRS) II score (mean difference [MD] -1.17, 95% CI -1.64 to -0.71), UPDRS III score (MD -1.55, 95% CI -2.29 to -0.81), and Schwab and England daily activity rating (MD 2.05, 95% CI 0.85–3.26). There was no statistically significant difference in the risk of serious adverse events (AEs) or discontinuation due to AEs in patients with LCE, and the risk of total AEs was higher in the LCE group (risk ratio [RR] 1.33, 95% CI 1.05–1.70). The incremental cost-effectiveness ratio of LCE was £3,105 per quality-adjusted life-year (QALY) gained in the UK.Conclusion: LCE can improve PD patients’ motor symptoms and daily living functioning when compared with levodopa/DDCI. Keywords: Unified Parkinson’s Disease Rating Scale, quality of life, wearing off, adverse events, cost-effectiveness, health technology assessment

Zhan-Miao Yi,1 Xiao-Jie Zhi,2 Ling Yang,3 Shu-Sen Sun,4 Zhuo Zhang,2 Zhi-Ming Sun,2 Suo-Di Zhai1 1Department of Pharmacy, Peking University Third Hospital, Beijing, People’s Republic of China; 2School of Pharmaceutical Science, 3School of Public Health, Peking University, Beijing, People’s Republic of China; 4College of Pharmacy, Western New England University, Springfield, MA, USA Background: Effective communication and education formats between health care providers and patients about medication use are associated with patients’ satisfaction, recall of information, and eventually their health status. Limited research exists on physician-delivered education interventions, as well as on whether the current content of medication education and delivery formats satisfies the needs of both patients and physicians. Our objective was to identify the practice gaps regarding medication education content and delivery.Methods: Separate surveys were obtained from ambulatory care patients presenting to the outpatient pharmacy for medication pickups, and physicians working at the hospital clinics.Results: A total of 108 patients completed the patient survey, and 116 hospital clinic physicians completed the physician survey. Female patients had a higher degree of concern regarding medication information compared with male patients (4.04±0.65 versus 3.58±0.66, P=0.001). Physicians were less likely to educate patients regarding their medications’ on drug–drug interactions (24.3%), drug–food interactions (24.3%), and what to do about their prescriptions if an adverse reaction is experienced (24.3%) during physician–patient encounters. Patients’ most desired education format was physician counseling (82.4%) and the second most desired education format was pharmacist counseling (50.9%). Medication device demonstration (7.0%) was the least used educational format delivered to patients by physicians, and patients would like to see an increased education delivery format through medication device demonstration (Method desired [MD] – Method received [MR] =12.0%). Patients would like to see expanded roles of patient focused handout (MD-MR=22.2%), telephone consultation (21.2%), pharmacist counseling (12.9%), the use of medication database embedded within the hospital information system (12.2%) and device demonstration (12.0%).Conclusion: This study illustrates that there are practice gaps in current medication education both in terms of content and delivery format. The study provided valuable information in designing and implementing future education activities that are drivers of good medication use and adherence. Keywords: medication education, medication adherence, degree of concern, education content, education format

Background: With the progress of therapeutic drug monitoring (TDM) technology and the development of evidence-based medicine, many guidelines were developed and implemented in recent decades., Objective: The aim was to evaluate the current status of TDM guidelines and provide suggestions for their development and updates based on Appraisal of Guidelines for Research and Evaluation (AGREE) II., Methods: The TDM guidelines were systematically searched for among databases including PubMed, Embase, China National Knowledge Infrastructure, Wanfang Data, and the Chinese biomedical literature service system and the official websites of TDM-related associations. The search period was from inception to 6 April 2023. Four researchers independently screened the literature and extracted data. Any disagreement was discussed and reconciled by another researcher. The quality of guidelines was assessed using the AGREE II instrument., Results: A total of 92 guidelines were included, including 57 technical guidelines, three management guidelines, and 32 comprehensive guidelines. The number of TDM guidelines has gradually increased since 1979. The United States published the most guidelines (20 guidelines), followed by China (15 guidelines) and the United Kingdom (ten guidelines), and 23 guidelines were developed by international organizations. Most guidelines are aimed at adult patients only, while 28 guidelines include special populations. With respect to formulation methods, there are 23 evidence-based guidelines. As for quality evaluation results based on AGREE II, comprehensive guidelines scored higher (58.16%) than technical guidelines (51.36%) and administrative guidelines (50.00%)., Conclusion: The number of TDM guidelines, especially technical and comprehensive ones, has significantly increased in recent years. Most guidelines are confronted with the problems of unclear methodology and low quality of evidence according to AGREE II. More evidence-based research on TDM and high-quality guideline development is recommended to promote individualized therapy., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: This meta-analysis was designed to investigate the associations between  SLCO1B1 , APOE  and CYP2C9  and the lipid-lowering effects and pharmacokinetics of fluvastatin. Methods: Studies were searched from inception to March 2023, including three SNPs related to fluvastatin, SLCO1B1 , CYP2C9 and  APOE . Weighted mean differences and corresponding 95% CIs were analyzed to evaluate the associations between SNPs and outcomes. Results: SLCO1B1 521T>C was associated with lower total cholesterol and low-density lipoprotein reduction. Patients carrying 521CC or total cholesterol had a significantly higher area under the curve than those carrying 521TT, but no significant difference existed. Conclusion: CYP2C9 and SLCO1B1 may be associated with the efficacy and pharmacokinetics of fluvastatin.

Background: In April 2009, the Chinese government launched Zero Markup Drug Policy (ZMDP) to adjust medical institutions' revenue and expenditure structures., Objective: This study evaluated the impact of implementing ZMDP (as an intervention) on the drug costs for managing Parkinson's disease (PD) and its complications from the healthcare providers' perspective., Methods: The drug costs for managing PD and its complications per outpatient visit or inpatient stay were estimated using electronic health data from a tertiary hospital in China from January 2016 to August 2018. An interrupted time series analysis was conducted to evaluate the immediate change following the intervention (step change, β 1 ) and the change in slope, comparing post-intervention with the pre-intervention period (trend change, β 2 ). Subgroup analyses were conducted in outpatients within the strata of age, patients with or without health insurance, and whether drugs were listed in the national Essential Medicine List (EML)., Results: Overall, 18,158 outpatient visits and 366 inpatient stays were included. Outpatient (β 1 = -201.7, 95%CI: -285.4, -117.9) and inpatient (β 1 = -372.1, 95% CI: -643.6, -100.6) drug costs for managing PD significantly decreased when implementing ZMDP. However, for outpatients without health insurance, the trend change in drug costs for managing PD (β 2 = 16.8, 95% CI: 8.0, 25.6) or PD complications (β 2 = 12.6, 95% CI: 5.5, 19.7) significantly increased. Trend changes in outpatient drug costs for managing PD differed when stratifying drugs listed in EML (β 2 = -1.4, 95% CI: -2.6, -0.2) or not (β 2 = 6.3, 95%CI: 2.0, 10.7). Trend changes of outpatient drug costs for managing PD complications significantly increased in drugs listed in EML (β 2 = 14.7, 95% CI 9.2, 20.3), patients without health insurance (β 2 = 12.6, 95% CI 5.5, 19.7), and age under 65 (β 2 = 24.3, 95% CI 17.3, 31.4)., Conclusions: Drug costs for managing PD and its complications significantly decreased when implementing ZMDP. However, the trend in drug costs increased significantly in several subgroups, which may offset the decrease at the implementation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Li, Gu, Cai, Wang, Yi and Chen.)

Aims: Infections are common complications after stroke and associated with unfavourable outcomes. We aimed to evaluate the efficacy and safety of prophylactic antibiotics for post-acute stroke infection., Methods: We searched PubMed, Embase, the Cochrane Library, SinoMed, China National Knowledge Infrastructure, WanFang Data, China Science and Technology Journal Database, and clinical trial register platforms from inception to 15 February 2022. We included randomized clinical trials that evaluated the efficacy and safety of prophylactic antibiotics. Primary outcomes were mortality rate and incidence of pneumonia. The pooled risk ratio (RR) and mean differences with 95% confidence interval (CI) were calculated using the random or fixed-effect model depending on heterogeneity. The quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations., Results: Twelve studies (4809 participants) were included. There was no significant difference in the mortality rate (12 trials, n = 4740, RR 1.03 [95% Cl: 0.91-1.16], high-quality evidence), incidence of pneumonia (7 trials, n = 4352, RR 0.94 [95% CI: 0.79-1.11], high-quality evidence) and the incidence of adverse events between the prophylactic antibiotics and control groups. Prophylactic antibiotics significantly reduced the incidence of infections (8 trials, n = 4517, RR 0.72 [95% CI: 0.58-0.89], moderate-quality evidence) and urinary tract infections (7 trials, n = 4352, RR 0.39 [95% CI: 0.3-0.49], moderate-quality evidence). None of the subgroup analyses showed a significant difference in mortality or the incidence of pneumonia., Conclusion: For acute stroke patients, prophylactic antibiotics were significantly associated with fewer incidences of any infections and urinary tract infections without significant differences in mortality rate and pneumonia., (© 2022 British Pharmacological Society.)

Background: With long-term pharmacotherapy, Parkinson's disease (PD) is expectedly to incur a significant healthcare burden. However, drug utilization and costing study is limited, so is the cost composition and its impact on resource allocation. This study took a healthcare provider's perspective to quantify medical and drug expenses and the utilization of drugs for managing PD and its complications., Methods: Medical resources use and associated cost of outpatient visits and inpatient admission episodes for PD patients were extracted from electronic medical records at a tertiary hospital in China from 1 January 2016 to 15 August 2018. Total and average direct medical (costs of outpatient visits and inpatient admission episodes) and drug costs were calculated during the study period and each calendar year. Drug cost was quantified by defined daily dose cost (DDDc) and levodopa equivalent dose cost (LEDc) per outpatient visit or inpatient admission episode for PD in Chinese yuan (¥), stratified by medication categories, and presented in descriptive statistics., Results: Overall, 18,158 outpatient visits and 366 inpatient admissions were incurred by 2,640 outpatients and 330 inpatients, with a median age of 71.0 and 73.5 years, respectively. Drug cost accounted for 97.82% and 23.33% of outpatient and inpatient medical expenditure. The average cost of drugs for managing PD accounted for 60.48% (¥952.50) and 2.70% (¥564.90) of cost per outpatient visit and inpatient episode, while drugs for managing PD complications was 11.38% and 0.70%, respectively. The highest DDDc and LEDc of drugs for managing PD per outpatient visit or inpatient episode were incurred by pramipexole (¥56.90-72.70 and ¥227.48-290.67) and entacapone (¥37.70-45.70 and ¥228.64-276.77). The DDDc and LEDc of pramipexole is more than 10 times that of levodopa/benserazide (DDDc: ¥4.90-5.70; LEDc: ¥10.14-11.98) and carbidopa/levodopa (DDDc: ¥4.00-5.00; LEDc: ¥11.02-13.95)., Conclusions: The outpatient direct medical cost for patients with PD was predominantly attributed to drug cost for managing PD, but drug cost weighed less of the inpatient cost. After adjusting the dose and number of patients, drugs with indirect dopamine effects had an excessively higher cost than dopamine precursors. Their long-term cost-effectiveness in real-world settings warrants further studies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-1014/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Objective: To identify the impact of a collaborative pharmaceutical care service (CPCS) on medication safety and establish the impact of the CPCS on patient reported outcomes for Parkinson's disease (PD) patients. Methods: Initially, PD outpatients receiving the CPCS between March 2017 and March 2019 were compared with PD patients receiving standard of care to identify differences in management. Pharmacist interventions data were coded and patients with PD receiving the CPCS were compared with those receiving standard of care to determine differences in medicines prescribed and dosage associated with these. Following this, data of patients receiving CPCS at baseline and 3-months follow-up were collected using a questionnaire consisting of validated measures of two patient-reported outcomes [adherence and quality of life (QoL)]. Mean scores for continuous variables were calculated, with descriptive analysis of categorical variables consisting of frequency counts and percentages. Change in adherence score before and after CPCS was investigated using a Wilcoxon sign rank sum test, spearman correlation analysis was used to correlate the changes in QoL before and after CPCS with the number of interventions, and p < 0.05 indicates that the difference is statistically significant. Results: A total of 331 PD outpatients received CPCS over 490 outpatient visits with an average age of 71.83 (±12.54). Five hundred and forty-five drug related problems were recorded as pharmacist interventions, of which most involved change to dosage ( n = 226, 41.47%), adverse drug reactions ( n = 135, 24.77%), and change in a medication ( n = 102, 18.72%). Compared with those receiving standard of care, patients receiving CPCS were significantly less likely to have been prescribed pramipexole (18.52 versus 23.77%, p < 0.001) and more likely to have been prescribed amantadine (5.40 versus 3.70%, p = 0.02) and selegiline (17.36 versus 11.64%, p < 0.001). Lower dosages of levodopa/benserazide (0.51 ± 0.31 g versus 0.84 ± 0.37 g, p < 0.001), levodopa/carbidopa (0.33 ± 0.23 g versus 0.66 ± 0.47 g, p < 0.001), pramipexole (1.14 ± 1.63 mg versus 1.27 ± 0.69 mg, p = 0.01), and entacapone (130.00 ± 79.76 mg versus 173.09 ± 97.86 mg, p < 0.001) were also recorded. At baseline 119 PD outpatients with an average age of 69.98 (±9.90) were recruited for the longitudinal study. At 3-month follow-up, participants reported improvement in bodily pain subscale (baseline versus 3-months follow-up, 30.04 ± 22.21 versus 23.01 ± 20.98, p = 0.037) and medication adherence (6.19 ± 1.50 versus 6.72 ± 1.73, p = 0.014). Frequency of CPCS use was related to activity of daily living subscale ( p = 0.047), the bodily pain subscale ( p = 0.026), and medication adherence ( p = 0.011). Total score of PDQ-39 was associated with patient education ( p = 0.005) and usage and dosage combined with patient education ( p = 0.006), while medication adherence score was associated with usage and dosage ( p = 0.005). Conclusion: The CPCS was effective in resolving drug-related problems and in improving patients' medication regimens, medication adherence, and QoL through patient education and dosage adjustments. This is the first step in the development and feasibility testing of pharmacy services for PD patients in China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yi, Willis, Zhang, Liu, Tang and Zhai.)

Background: The International Pharmaceutical Federation (FIP) has established an interim guidance of coronavirus disease 2019 (COVID-19) for pharmacists worldwide. The aim of this study was to identify the implementation of FIP guidance in China and provide applicable strategies for further actions., Methods: A nationwide cross-sectional survey on Chinese pharmacists was distributed electronically through groups of WeChat between 9 December 2020 and 18 December 2020. The 29-item questionnaire for the survey was designed based on the FIP guidance and knowledge, attitudes, and practices (KAP) framework., Results: A total of 237 responses from 237 pharmacists (69.20% females) were received. Most pharmacists (81.86%) participated in work related to COVID-19. Respondents referred to other guidelines or consensus more than they did to FIP guidance. Most participants were qualified for the knowledge-based questions regarding COVID-19 (67.51%), had positive attitudes towards pharmacists' roles and actions (61.18%), and were qualified in the practices of prevention measures, infection risk monitoring, and pharmacists' advice (50.63%). Several factors were revealed as having impact on pharmacists' KAP, such as the relevance of participating in work related to COVID-19, work entailments, and information source., Conclusions: The FIP guidance has a certain degree of dissemination and implementation in China, which can be improved through effective actions directed towards impact factors., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-4157). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Objective: To explore the role of pharmacists and innovation of pharmacy interventions for COVID-19 patients in China., Methods: We comprehensively searched PubMed and Chinese databases Sinomed, China National Knowledge Infrastructure to identify articles reporting pharmacist interventions and pharmacy services for COVID-19 patients using a predefined search strategy. The search period was from inception to April 7 th 2020. We also manually searched the reference list of included articles and websites of important journals with special issues for COVID-19., Results: A total of 156 articles were identified by applying the search criteria. After screening, 91 articles, with the majority are literature reviews (n = 77, 84.62%) published in Chinese (n = 83, 91.2%), were included. Pharmacist interventions for COVID-19 patients most commonly related to guidelines or consensus development for the treatment of disease and practice procedure to prevent the spread of COVID-19 (n = 10, 10.98%), the supply of medicines to treat patients with severe respiratory or systematic symptoms related to COVID-19 (n = 10, 10.98%), formulating infections prevention and control strategies related to COVID-19 for pharmaceutical personnel/pharmacy staff (n = 14, 15.39%), new way of delivery pharmacy services and the implementation of new pharmacy services for COVID-19 outbreak (n = 14, 15.39%), routine pharmacy services under the restrict limit of COVID-19 outbreak (n = 39, 42.86%), and case series analysis of treatment regimens using existing, routinely collected data (n = 4, 4.40%)., Conclusion: Pharmacy services have a role in the COVID-19 pandemic control, and there were many rapid changes in response to the pandemic., (Copyright © 2020 Yi, Hu, Wang and Zhao.)

Globalization has attracted much attention to universities over the past decade. The aim of this study was to evaluate the effect of the United States-China international pharmacy education programs (IPEP) in China.Kirkpatrick's model of evaluation was used to evaluate IPEP from reaction and learning levels. In the reaction level, a questionnaire survey with a Likert scale was used. In the learning level, data from "Assessment Record of Advanced Clinical Pharmacy Practice of Peking University" were collected. Cronbach' α coefficient of reliability was calculated, principal component analysis and independent t-test were conducted.All of the students who attended IPEP (n = 36) completed the questionnaire survey. The scores of benefits were increased in 4 categories, including "Clinical practice competency improvement" (mean ranking [MR] = 3.11 points), "Understanding of doctor of Pharmacy education mode" (MR = 3.48 points), "English competency improvement" (MR = 3.64 points) and "International collaboration" (MR = 3.92 points). Meanwhile, the overall satisfaction was relatively high with the IPEP (MR = 4.22 points). In the learning level, a total of 22 records was obtained. Students who attended (n = 5) the IPEP achieved higher scores than those did not attend (n = 17) in the assessment records, although no statistical significant differences were observed. Personal in-depth interviews further supported the overall benefit of IPEP.The Kirkpatrick model of evaluation can be used for IPEP. The benefit and satisfaction of students attended the IPEP were high in the reaction level; even though no statistically significant difference was shown in the learning level, higher scores were still demonstrated.

Background: Medicines optimisation is important for the management of Parkinson's disease (PD). As many patients with PD have other long-term conditions, treatment is complex and risk of adverse events for these patients is high., Objective: To explore the role of pharmacists and impact of pharmacy interventions for PD patients., Methods: We comprehensively searched PubMed, Embase, the Cochrane Library and Chinese databases Sinomed, China National Knowledge Infrastructure to identify studies reporting pharmacist interventions and pharmacy services for PD patients using a predefined search strategy. The search period was from inception to March 2019. We also manually searched the reference list of included studies and ClinicalTrials.gov. We conducted meta-analyses to synthesize the evidence quantitatively., Results: A total of 1607 studies were identified by applying the search criteria. After screening, 19 cross-sectional and case-controlled studies with 1458 PD patients from 9 countries were included. Pharmacist interventions for PD patients most commonly related to adverse drug reactions (ADRs) (13 studies), adherence assessment (12 studies), medication review (12 studies), identification of drug interactions (11 studies), monitoring response to medication therapy (11 studies), identification of inappropriate medication (11 studies), and patient education (10 studies). Most pharmacy services were provided in outpatient settings (13 studies). Reported impact measures included adherence (8 studies), quality of life (7 studies), and identification of drug-related problems (6 studies) such as ADRs (393 times out of 1760 times, 22.33%, 6 studies), inappropriate drug choice (349 times, 19.83%, 6 studies), inappropriate dosage (335 times, 19.03%, 6 studies), inappropriate drug use (257 times, 14.60%, 3 studies) and drug-drug interactions (146 times, 8.3%, 4 studies). Pooled results from 3 studies indicated no statistically significant impact of pharmacy services on all subscales of PD Questionnaire-39., Conclusion: ADRs were the most widely reported drug-related problems for PD patients; pharmacy services may have a role to play in medication adherence but were not found to impact on quality of life.

Background: Both amisulpride and olanzapine are leading treatments for schizophrenia in China. This study aimed to investigate the long-term cost-effectiveness of amisulpride and olanzapine in the treatment of schizophrenia in China., Methods: A decision-analytic Markov model was developed to simulate the lifetime clinical and economic outcomes of schizophrenia treatment from the healthcare payer perspective. The long-term costs and QALYs were estimated. Sensitivity analyses were performed to explore the impact of variance of parameters on the results., Results: Treatment with amisulpride provided an effectiveness gain of 16.59 QALYs at an average cost of USD 25,884 whereas olanzapine resulted in 16.38 QALYs at a cost of USD 34,839 over a lifetime horizon. One-way sensitivity analysis suggested that the most sensitive variable was the unit cost of olanzapine. In a probabilistic sensitivity analysis based on a Monte Carlo simulation with a lifetime horizon, the probability of amisulpride being cost-effective was 99.8% at a willingness-to-pay threshold of USD 9,322, the GDP per capita in China 2018. A scenario analysis with updated olanzapine unit cost suggested an ICER of 7,857 USD/QALY., Conclusions: Amisulpride is likely to be a cost-effective option with increased effectiveness compared with olanzapine in the treatment of schizophrenia patients in China.

Fulminant type 1 diabetes mellitus (FT1DM) has received clinical attention for its low incidence and poor prognosis. Currently, few cases of FT1DM are associated with pregnancy in clinical practice, but it poses a great threat to the life of mothers and infants. Here, we present two cases of FT1DM in pregnancy. In Case 1, the patient was a 26-year-old woman who was admitted to the hospital with reduced fetal movement. She was diagnosed with FT1DM and delivered a dead female fetus. Lispro and lantus were administered to control blood glucose, and lipoic acid for antioxidant therapy. In Case 2, the patient was a 28-year-old woman who developed nausea, vomiting, diarrhea, and polydipsia, which later proved to be FT1DM. An abortion was induced and blood glucose levels were controlled using an insulin pump. All physicians should be aware of this disease in order to provide prompt diagnosis and emergency treatment, thus improving maternal prognosis. We suggest that plasma glucose/hemoglobin A1C ratio be adopted as a new clinical parameter in predicting FT1DM.

Objectives : We aimed to conduct a modelling study to estimate and predict the economic burden of AD to support the healthcare management of AD in China. Methods : The economic burden of AD was estimated with an evaluation of the prevalence of AD patients and a simulation of annual resource use and cost per AD patient in China using a published model. Percentage of AD patients being treated was assumed to be 5% from 2010 to 2050, with three scenarios testing the value of this parameter of 10%, 20% and 40% throughout 2020 to 2050. Results : The costs of AD were estimated to be from around 91 billion RMB in 2010 to 332 billion in 2050. Most of the current burden was related to private caregivers paid by families. With the percentage of patients being treated changing from 5% to 40%, costs were estimated to double. This was related to more hospitalisations and more use of care facilities, while the burden for families would decrease. Conclusion : A high economic burden related to AD is predicted. The burden would be driven mainly by indirect costs related to the social support of the patients. Investment in improving awareness and care of AD patients is needed and worth it., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Backgroud: Evidence on the efficacy and safety of sertraline in patients with premature ejaculation (PE) was inconsistent. The objective of this article is to evaluate the efficacy and safety of sertraline for the treatment of PE., Methods: We searched Medline (OVID), Embase, the Cochrane Library, and 2 Chinese databases for randomized controlled trials (RCTs) and randomized crossover trials (RTs) that evaluated the efficacy and safety of sertraline in patients with PE. A meta-analysis was performed to calculate their pooled estimates with 95% confidence interval., Results: Of the 645 records obtained, we included 12 RCTs and 2 RTs (n = 977). Meta-analysis showed that sertraline prolonged intravaginal ejaculation latency time (IELT) in PE patients ((standard mean difference (SMD) = 2.14, 95% CI 1.20 to 3.08). Subgroup analyses indicated a prolonged IELT for different treatment courses: 4 weeks (SMD = 2.66, 1.06 to 4.26), 6 weeks (SMD = 0.95, 0.31 to 1.58), and 8 weeks (SMD = 1.81, 0.78 to 2.85). The sexual satisfaction rates of patients (SMD = 2.20, 1.57 to 2.84) and spouses (SMD = 2.27, 1.44 to 3.09) were also improved. We observed a significant increased risk of gastrointestinal upset (risk ratio = 2.71, 1.39 to 5.28) in the sertraline group., Conclusion: Sertraline can prolong IELT of PE patients, improve sexual satisfaction rates of patients and spouses, but increase risk of gastrointestinal upset.

Background: The high prevalence of transfusion-transmitted infections (TTIs) is causing serious harm to human health worldwide. The aim of this research was to assess the prevalence and influencing factors of TTIs in Southwest China., Methods: A retrospective study of blood donor records from January 2008 to December 2015 was conducted. All samples were screened for HBV, HCV, HIV and syphilis. The donor's data was recorded and analyzed statistically using SPSS software., Results: We revealed that the prevalence of TTIs showed a decreasing trend from 2.39 to 1.98%, and this was slightly lower than that in other regions of China. Syphilis infection was the most serious issue among blood donors in Southwest China, which demonstrated a significantly higher rate than that in other areas of China. The high infection rate of the female and farmer groups in rural regions is worth noting. The logistic regression model showed that age, occupation and donor category was the influential factors for TTIs., Conclusions: The overall prevalence of TTIs demonstrated a decreasing trend from 2008 to 2015 in Southwest China, but there is still a sufficient threat to blood safety, and more efforts are needed to further guarantee blood safety in China., (© The Author(s) 2018. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: We compared prophylactic effects of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H 2 RAs) on upper gastrointestinal bleeding (UGIB) associated with dual antiplatelet therapy (DAPT) and explored this influence on platelet function., Methods: Randomized controlled trials and cohort studies comparing PPIs with H 2 RAs in adults receiving DAPT were collected from PubMed, EMBASE and Cochrane databases. Dichotomous data were pooled to obtain risk ratios (RRs) for UGIB, major adverse cardiovascular events (MACEs), poor responders to clopidogrel and rehospitalization, and continuous data were pooled to obtain mean differences (MDs) for P2Y 12 reaction units (PRUs), with 95% confidence intervals (CIs)., Results: Twelve clinical trials (n=3,301) met the inclusion criteria. Compared to H 2 RAs, PPIs lessened UGIB (RR =0.16, 95% CI: 0.03-0.70), and there was no significant difference in the incidence of PRUs (MD =18.21 PRUs, 95% CI: -4.11-40.54), poor responders to clopidogrel (RR =1.21, 95% CI: 0.92-1.61), incidence of MACEs (RR =0.89, 95% CI: 0.45-1.75) or rehospitalization (RR =1.76, 95% CI: 0.79-3.92). Subgroup analysis confirmed fewer PRUs in the H 2 RAs group compared to the omeprazole group (2 studies, n=189, MD =31.80 PRUs, 95% CI: 11.65-51.96). However, poor responder data for clopidogrel and MACEs might be unreliable because few studies of this kind were included., Conclusion: Limited evidence indicates that PPIs were better than H 2 RAs for prophylaxis of UGIB associated with DAPT and had no effect on platelet function. Further study is needed to confirm these observations., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Medications used to treat neurological diseases may result in adverse effects. Research is needed to demonstrate pharmacist value and their roles in patient care., Objective: To categorize the types and severities of the prescribing errors intercepted and to describe clinical activities conducted by neurology ward pharmacists., Method: Pharmacists prospectively reviewed medication orders over an 18-month period with inventions documented and categorized., Results: A total of 341 prescribing errors in 1183 patients were intercepted. The most common error types were dosing frequency (35.8 %) and medication selection (21.5 %). The top five most detected error medications were those indicated for hyperhomocysteinemia (22.0 %), stress ulcer prophylaxis (12.3 %), poor circulation (10.9 %), hyperglycemia (6.5 %), and infections (5.9 %). Although 67.5 % of the detected errors having the potential causing no harm, 26.4 % of the errors may require intervention, and 6.2 % may increase the length of stay. The number of errors decreased from 19 to 10 per month during the study period. Clinical pharmacists also actively engaged in medication use evaluation, clinical decision support system optimization, and education to patients and providers., Conclusion: Presence of clinical pharmacists at the neurology unit may help in early detection of prescribing errors with increased patient safety.

Prophenoloxidase (PPO) is an essential enzyme in insect innate immunity because of its role in humoral defense. In this study, we have cloned a full-length cDNA of Antheraea pernyi prophenoloxidase (ApPPO) with an open-reading frame encoding 683 amino acids, and the deduced amino acid sequence of ApPPO exhibited a high similarity with those of lepidoptera. The expression of ApPPO was inducible so that the mRNA level was significantly upregulated in the microbial challenged tissues, including fat body, hemocytes, and midgut. To better investigate the enzymatic and immunological properties of ApPPO, recombinant ApPPO (rApPPO) was produced in Escherichia coli. Several functional verification experiments were performed after studying the enzymatic properties. It was found that rApPPO could be stimulated by the microbial challenged larvae hemolymph and then killed bacteria in the radial diffusion assay. Furthermore, rApPPO also induced the transcription of cecropins after injected into the larvae 24 h later., (© 2014 Wiley Periodicals, Inc.)

Unlabelled: Entecavir is a potent antiviral agent with high genetic barrier to resistance, hence it is currently recommended as first-line antiviral therapy for chronic hepatitis B (CHB). The aim of this study was to investigate the efficacy of entecavir on clinical outcomes and deaths. It was a retrospective-prospective cohort study based on two cohorts of patients. The entecavir cohort included consecutive CHB patients who had received entecavir 0.5 mg/day for at least 12 months. The historical control cohort included untreated patients recruited since 1997 who underwent routine clinical care. The primary outcome was the 5-year cumulative probability of hepatic events, defined as any cirrhotic complications, hepatocellular carcinoma (HCC), and/or liver-related mortality. A total of 1,446 entecavir-treated patients (72% men; age, 51 ± 12 years; follow-up, 36 ± 13 months) and 424 treatment-naïve patients (65% men; age, 41 ± 13 years; follow-up, 114 ± 31 months) were studied. Overall, there was no difference in hepatic events between the entecavir and control cohorts. Among patients with liver cirrhosis (482 entecavir-treated, 69 treatment-naïve), entecavir-treated patients had reduced risks of all clinical outcomes when compared with treatment-naïve patients with cirrhosis after adjusted for model for end-stage liver disease score: hepatic events (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.34-0.78; P = 0.002), HCC (HR, 0.55; 95% CI, 0.31-0.99; P = 0.049), liver-related mortality (HR, 0.26; 95% CI, 0.13-0.55; P < 0.001), and all-cause mortality (HR, 0.34; 95% CI, 0.18-0.62; P < 0.001). Entecavir-treated patients with cirrhosis who failed to achieve undetectable hepatitis B virus DNA (105/482 [22%]) had comparable risk of hepatic events as the untreated patients., Conclusion: Entecavir therapy reduces the risks of hepatic events, HCC, liver-related and all-cause mortality of CHB patients with liver cirrhosis in 5 years, particularly among those who had maintained viral suppression., (Copyright © 2013 American Association for the Study of Liver Diseases.)

Background & Aims: Little is known about the validity of hepatocellular carcinoma (HCC) risk scores derived from treatment-naïve patients with chronic hepatitis B for patients treated with entecavir., Methods: We performed a retrospective-prospective cohort study of 1531 patients with chronic hepatitis B (age, 51 ± 12 years; 1099 male; 332 with clinical cirrhosis) who were treated with entecavir 0.5 mg daily for at least 12 months at Prince of Wales Hospital in Hong Kong from December 2005 to August 2012. The patients were assessed once every 3 to 6 months for symptoms, drug history, and adherence; blood samples were collected for biochemical analyses. We validated 3 HCC risk scores (CU-HCC, GAG-HCC, and REACH-B scores) based on data collected when patients began treatment with entecavir and 2 years later., Results: After 42 ± 13 months of follow-up, 47 patients (2.9%) developed HCC. The 5-year cumulative incidence of HCC was 4.3% (95% confidence interval [CI], 3.6%-5.0%). Older age, presence of cirrhosis, and virologic remission after 24 months or more of therapy were independently associated with HCC in the entire cohort; advanced age and hypoalbuminemia were associated with HCC in patients without cirrhosis. The area under the receiver operating characteristic curves (AUCs) for baseline CU-HCC, GAG-HCC, and REACH-B scores for HCC were 0.80 (95% CI, 0.75-0.86), 0.76 (95% CI, 0.70-0.82), and 0.71 (95% CI, 0.62-0.81), respectively; the time-dependent AUCs 1 to 4 years after patients started treatment were comparable to those at baseline. The cutoff value of the baseline CU-HCC score identified patients who would develop HCC with 93.6% sensitivity and 47.8% specificity, the baseline GAG-HCC score with 55.3% sensitivity and 78.9% specificity, and the baseline REACH-B score with 95.2% sensitivity and 16.5% specificity. Compared with patients with CU-HCC scores <5 at baseline, those with CU-HCC scores that either decreased from ≥5 to <5 or remained ≥5 had a higher risk of HCC (5-year cumulative incidences, 0% vs 3.9% and 7.3%; P = .002 and P < .001, respectively)., Conclusions: The CU-HCC, GAG-HCC, and REACH-B HCC risk scores accurately predict which patients with chronic hepatitis B treated with entecavir will develop HCC., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Data concerning the extent of off-label prescriptions for adult neurological patients are limited, and the method of assessing supporting evidence in previous studies has some limitations., Objective: To improve the method of assessing supporting evidence, determine the status of off-label prescriptions for adult neurological patients, and evaluate the varying levels of supporting evidence., Setting: Single, 1,264-bed, tertiary care university hospital in Beijing, China., Method: This was a pilot retrospective observational study for adult neurological patients during the period of March 22nd-28th, 2010. Off-label prescriptions were defined according to package inserts. The DRUGDEX system was used to evaluate supporting evidence initially; when information was not available, PubMed/CBM was searched and the grading system proposed by Oxford Centre for Evidence-Based Medicine (OCEBM) was used for categorizing supporting evidence alternatively., Main Outcome Measure: Types, main therapeutic classes and main neurological diseases involved, evidence and recommendation strengths of off-label prescriptions., Results: A total of 418 off-label prescriptions were identified from 3,187 prescriptions for 966 patients, 193 from 759 inpatient (25.4%) and 225 from 2,428 outpatient care (9.3%). Most off-label prescriptions were related to unapproved indications. These off-label prescriptions mainly included drugs labeled for nervous system diseases, cerebrovascular diseases, anemia and ophthalmic conditions; and the medication orders were mostly for cerebrovascular diseases. A total of 155 (37.1%) were initially searched and evaluated in the DRUGDEX system; the remaining 263 (62.9%) prescriptions were found in PubMed/CBM search and evaluated by the OCEBM grading system. Sixty-six (34.2%) off-label prescriptions from inpatients and 103 (45.8%) from outpatients were categorized as Class III or Grade D recommendations., Conclusions: The improved method provided a supplementary way to study off-label uses. Off-label prescriptions for adult neurological patients mainly concerned unapproved indications, nervous system agents and cerebrovascular diseases, and many of them had inferior level of evidence.

Background: Depression may affect patients' recovery and even their survival rate after stroke, but it is often overlooked or inadequately managed; data regarding the prophylactic efficacy and safety of fluoxetine are inconsistent in this setting., Objective: The objective of the study is to systematically assess the prophylactic efficacy and safety of fluoxetine for poststroke depression in patients with stroke., Methods: We searched electronic databases up to December 2009 for studies evaluating the prophylactic efficacy of fluoxetine in patients with stroke. The pooled odds ratio (OR), weighted mean difference (WMD), incremental efficiency and 95% confidence intervals (95% CI) were calculated., Results: We collected and evaluated a total of 385 patients identified from six trials. Meta-analysis demonstrated that fluoxetine reduced the incidence of poststroke depression (PSD) (OR = 0.25, 95% CI 0.11 to 0.56), helped recovery in neurological function (WMD = -4.72, 95% CI -8.31 to -1.13) and improved independence in activities of daily living (WMD = -8.04, 95% CI -13.40 to -2.68); fluoxetine is relatively safe in spite of the adverse events (OR = 0.88, 95% CI 0.31 to 2.49, p = 0.82). However, fluoxetine groups and control groups did not differ in change of scores for depression (WMD = -3.97, 95% CI -9.85 to 1.90, p = 0.19)., Conclusions: Fluoxetine was beneficial for the prophylaxis of poststroke depression in patients with stroke but not in reducing symptom severity of PSD.

Objective: To investigate the characteristics of bacteriology and the drug resistance in the patients with chronic obstructive disease (COPD) combined with pneumonia at our respiratory intensive care unit(RICU) in 2001., Methods: The sputum of 543 patients with COPD combined with pneumonia was collected with a regular method, the bacteria were cultured, and then the drug sensitivity was analyzed with K-B method., Results: There were 181 positive samples in the 543 patients with the positive rate 33.9%. The main bacteria in the G- bacillus were Pseudomonas (21.55%), Haemophilus influenza (14.36%), Enteric bacilli (13.26%), and Klebsiella (11.60%) which were sensitive to impipenem, amikacin, and ceftazidime. The main bacteria in G+ bacteria were Staphylococcus aureus (7.18%) and Staphylococcus epidermindis (4.42%) which were sensitive to vancomycin, imipenem, ceftazidime, and amikacin., Conclusion: The bacteria in the patients with COPD combined with pneumonia at RICU of the hospital in 2001 are mainly made up of G- bacillus and secondarily of G+ bacteria which are sensitive to imipenem, amikacin, and ceftazidime. The G+ bacteria are highly sensitive to vancomycin.