Status and Quality of Guidelines for Therapeutic Drug Monitoring Based on AGREE II Instrument.

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.

Associations between SLCO1B1, APOE and CYP2C9 and lipid-lowering efficacy and pharmacokinetics of fluvastatin: a meta-analysis.

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.

The impact of China's zero markup drug policy on drug costs for managing Parkinson's disease and its complications: an interrupted time series analysis.

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, ß1) and the change in slope, comparing post-intervention with the pre-intervention period (trend change, ß2). 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 (ß1 = -201.7, 95%CI: -285.4, -117.9) and inpatient (ß1 = -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 (ß2 = 16.8, 95% CI: 8.0, 25.6) or PD complications (ß2 = 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 (ß2 = -1.4, 95% CI: -2.6, -0.2) or not (ß2 = 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 (ß2 = 14.7, 95% CI 9.2, 20.3), patients without health insurance (ß2 = 12.6, 95% CI 5.5, 19.7), and age under 65 (ß2 = 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.

Efficacy and safety of selegiline for the treatment of Parkinson's disease: A systematic review and meta-analysis.

Background: Drug efficacy generally varies with different durations. There is no systematic review analyzing the effect of selegiline for Parkinson's disease (PD) on different treatment duration. This study aims to analyze how the efficacy and safety of selegiline changes for PD over time. Methods: PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure and Wanfang Database were systematically retrieved for randomized controlled trials (RCTs) and observational studies of selegiline for PD. The search period was from inception to January 18th, 2022. The efficacy outcomes were measured by the mean change from baseline in the total and sub Unified Parkinson's Disease Rating Scale (UPDRS), Hamilton Depression Rating Scale (HAMD) and Webster Rating Scale (WRS) scores. The safety outcomes were measured by the proportion of participants having any adverse events overall and that in different system organ classes. Results: Among the 3,786 studies obtained, 27 RCTs and 11 observational studies met the inclusion criteria. Twenty-three studies reported an outcome which was also reported in at least one other study, and were included in meta-analyses. Compared with placebo, selegiline was found with a stronger reduction of total UPDRS score with increasing treatment duration [mean difference and 95% CIs in 1 month: -3.56 (-6.67, -0.45); 3 months: -3.32 (-3.75, -2.89); 6 months: -7.46 (-12.60, -2.32); 12 months: -5.07 (-6.74, -3.41); 48 months: -8.78 (-13.75, -3.80); 60 months: -11.06 (-16.19, -5.94)]. A similar trend was also found from the point estimates in UPDRS I, II, III, HAMD and WRS score. The results of observational studies on efficacy were not entirely consistent. As for safety, compared with placebo, selegiline had higher risk of incurring any adverse events [rate: 54.7% vs. 62.1%; odd ratio and 95% CIs: 1.58 (1.02, 2.44)], with the excess adverse events mainly manifested as neuropsychiatric disorders [26.7% vs. 31.6%; 1.36 (1.06, 1.75)] and no significant change over time. The statistically difference in overall adverse event between selegiline and active controls was not found. Conclusion: Selegiline was effective in improving total UPDRS score with increasing treatment duration, and had a higher risk of incurring adverse events, especially the adverse events in the neuropsychiatric system. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: PROSPERO CRD42021233145.

The efficacy and safety of prophylactic antibiotics for post-acute stroke infection: A systematic review and meta-analysis.

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.

Evaluating the direct medical cost, drug utilization and expenditure for managing Parkinson's disease: a costing study at a medical center in China.

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.

The implementation of a FIP guidance for COVID-19: insights from a nationwide survey.

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.

Impact of a Collaborative Pharmaceutical Care Service for Patients With Parkinson's Disease.

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.

Mapping Evidence of Pharmacy Services for COVID-19 in China.

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 7th 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.

Effect of the international pharmacy education programs: A pilot evaluation based on Kirkpatrick's model.

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.

Efficacy, Safety, and Economics of Intravenous Levetiracetam for Status Epilepticus: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate efficacy, safety, and economics profiles of intravenous levetiracetam (LEV) for status epilepticus (SE). METHODS: We searched PubMed, Embase, the Cochrane Library, Clinicaltrials.gov, and OpenGrey.eu for eligible studies published from inception to June 12th 2019. Meta-analyses were conducted using random-effect model to calculate odds ratio (OR) of included randomized controlled trials (RCTs) with RevMan 5.3 software. RESULTS: A total of 478 studies were obtained. Five systematic reviews (SRs)/meta-analyses, 9 RCTs, 1 non-randomized trial, and 27 case series/reports and 1 economic study met the inclusion criteria. Five SRs indicated no statistically significant difference in rates of seizure cessation when LEV was compared with lorazepam (LOR), phenytoin (PHT), or valproate (VPA). Pooled results of included RCTs indicated no statistically significant difference in seizure cessation when LEV was compared with LOR [OR = 1.04, 95% confidence interval (CI) 0.37 to 2.92], PHT (OR = 0.90, 95% CI 0.64 to 1.27), and VPA (OR = 1.47, 95% CI 0.81 to 2.67); and no statistically significant difference in seizure freedom within 24 h compared with LOR [OR = 1.83, 95% CI 0.57 to 5.90] and PHT (OR = 1.08, 95% CI 0.63 to 1.87). Meanwhile, LEV did not increase the risk of mortality during hospitalization compared with LOR (OR = 1.03, 95% CI 0.31 to 3.39), PHT (OR = 0.89, 95% CI 0.37 to 2.10), VPA (OR = 1.28, 95% CI 0.32 to 5.07), and placebo (plus clonazepam, OR = 0.73, 95% CI 0.16 to 3.38). LEV had lower need for artificial ventilation (OR = 0.23, 95% CI 0.06 to 0.92) and a lower risk of hypotension (OR = 0.15, 95% CI 0.03 to 0.84) compared to LOR. A trend of lower risk of hypotension and higher risk of agitation was found when LEV was compared with PHT. Case series and case report studies indicated psychiatric and behavioral adverse events of LEV. Cost-effectiveness evaluations indicated LEV as the most cost-effective non-benzodiazepines anti-epileptic drug (AED). CONCLUSIONS: LEV has a similar efficacy as LOR, PHT, and VPA for SE, but a lower need for ventilator assistance and risk of hypotension, thus can be used as a second-line treatment for SE. However, more well-conducted studies to confirm the role of intravenous LEV for SE are still needed.

Content and impact of pharmacy services for patients with Parkinson's disease: A systematic review and meta-analysis.

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.

Comparative cost-effectiveness of amisulpride and olanzapine in the treatment of schizophrenia in China.

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.

Economic burden for Alzheimer's disease in China from 2010 to 2050: a modelling study.

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.

Efficacy and safety of sertraline for the treatment of premature ejaculation: Systematic review and meta-analysis.

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.

Levetiracetam for epilepsy: an evidence map of efficacy, safety and economic profiles.

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).

Levodopa/carbidopa/entacapone versus levodopa/dopa-decarboxyiase inhibitor for the treatment of Parkinson's disease: systematic review, meta-analysis, and economic evaluation.

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.

Comparison of prophylactic effect of UGIB and effects on platelet function between PPIs and H2RAs combined with DAPT: systematic review and meta-analysis.

OBJECTIVE: We compared prophylactic effects of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) 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 H2RAs 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 P2Y12 reaction units (PRUs), with 95% confidence intervals (CIs). RESULTS: Twelve clinical trials (n=3,301) met the inclusion criteria. Compared to H2RAs, 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 H2RAs 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 H2RAs for prophylaxis of UGIB associated with DAPT and had no effect on platelet function. Further study is needed to confirm these observations.

An evaluation of clinical pharmacist service on a neurology care unit.

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.