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.

Efficacy and Safety Profile of Novel Oral Anticoagulants in the Treatment of Left Atrial Thrombosis: A Systematic Review and Meta-Analysis.

Background: The presence of left atrial/left atrial appendage thrombosis is associated with a higher risk of thromboembolic events in patients with atrial fibrillation. The optimal antithrombotic strategy is not established to date. Objective: Our aim was to compare the efficacy and safety profile of novel oral anticoagulants with warfarin in the treatment of left atrial/left atrial appendage thrombosis. Methods: We conducted a systematic search in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and 3 Chinese databases for all randomized controlled trials and cohort studies (PROSPERO, CRD42021238952) from inception to 7 May 2021. Two authors independently performed the articles selection, data extraction, and quality assessment. The efficacy outcome was the resolution of left atrial/left atrial appendage thrombosis, and the safety outcomes were bleeding and stroke/transient ischemic attack. Results: One randomized controlled trial and 5 cohort studies were included, with a total of 353 patients. Compared with warfarin, novel oral anticoagulants were associated with increased probability of left atrial/left atrial appendage thrombosis resolution (OR = 2.20; 95% CI, 1.35-3.60; I 2 = 0%). Compared with warfarin, novel oral anticoagulants had a similar risk of bleeding (OR = 0.91; 95% CI, 0.39-2.13; I 2 = 0%). There was no evidence of increased risk of stroke/transient ischemic attack (OR = 0.42; 95% CI, 0.12-1.45; I 2 = 0%). Conclusions: Novel oral anticoagulants were more effective than warfarin in promoting the resolution of left atrial/left atrial appendage thrombosis, without increased risks of bleeding and stroke/transient ischemic attack. Our study provides valuable insight into clinical practice. Further well-designed randomized controlled trials are needed to fully evaluate the benefits and risks in these patients. PROSPERO Registration No.: CRD42021238952.

Dopamine agonists for preventing ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism, and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Dopamine agonists were introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment.  OBJECTIVES: To assess the effectiveness and safety of dopamine agonists in preventing OHSS in women at high risk of developing OHSS when undergoing ART treatment. SEARCH METHODS: We searched the following databases from inception to 4 May 2020: Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO for randomised controlled trials (RCTs) assessing the effect of dopamine agonists on OHSS rates. We also handsearched reference lists and grey literature. SELECTION CRITERIA: We considered RCTs for inclusion that compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in ART. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary outcomes were rates of clinical pregnancy, multiple pregnancy, miscarriage, and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts, and full texts of publications; selected studies; extracted data; and assessed risk of bias. We resolved disagreements  by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. We applied GRADE criteria to judge overall quality of the evidence. MAIN RESULTS: The search identified six new RCTs, resulting in 22 included RCTs involving 3171 women at high risk of OHSS for this updated review. The dopamine agonists were cabergoline, quinagolide, and bromocriptine. Dopamine agonists versus placebo or no intervention Dopamine agonists probably lowered the risk of moderate or severe OHSS compared to placebo/no intervention (OR 0.32, 95% CI 0.23 to 0.44; 10 studies, 1202 participants; moderate-quality evidence). This suggests that if the risk of moderate or severe OHSS following placebo/no intervention is assumed to be 27%, the risk following dopamine agonists would be between 8% and 14%. We are uncertain of the effect of dopamine agonists on rates of live birth (OR 0.96, 95% CI 0.60 to 1.55; 3 studies, 362 participants; low-quality evidence). We are also uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy, miscarriage  or adverse events (very low to low-quality evidence). Dopamine agonists plus co-intervention versus co-intervention Dopamine agonist plus co-intervention (hydroxyethyl starch, human albumin, or withholding ovarian stimulation 'coasting') may decrease the risk of moderate or severe OHSS compared to co-intervention (OR 0.48, 95% CI 0.28 to 0.84; 4 studies, 748 participants; low-quality evidence). Dopamine agonists may improve rates of live birth (OR 1.21, 95% CI 0.81 to 1.80; 2 studies, 400 participants; low-quality evidence). Dopamine agonists may improve rates of clinical pregnancy and miscarriage, but we are uncertain if they improve rates of multiple pregnancy  or adverse events (very low to low-quality evidence). Dopamine agonists versus other active interventions We are uncertain if cabergoline improves the risk of moderate or severe OHSS compared to human albumin (OR 0.21, 95% CI 0.12 to 0.38; 3 studies, 296 participants; very low-quality evidence), prednisolone (OR 0.27, 95% CI 0.05 to 1.33; 1 study; 150 participants; very low-quality evidence), hydroxyethyl starch (OR 2.69, 95% CI 0.48 to 15.10; 1 study, 61 participants; very low-quality evidence), coasting (OR 0.42, 95% CI 0.18 to 0.95; 3 studies, 320 participants; very low-quality evidence), calcium infusion (OR 1.83, 95% CI 0.88 to 3.81; I² = 81%; 2 studies, 400 participants; very low-quality evidence), or diosmin (OR 2.85, 95% CI 1.35 to 6.00; 1 study, 200 participants; very low-quality evidence). We are uncertain of the effect of dopamine agonists on rates of live birth (OR 1.08, 95% CI 0.73 to 1.59; 2 studies, 430 participants; low-quality evidence). We are uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy or miscarriage (low to moderate-quality evidence). There were no adverse events reported. AUTHORS' CONCLUSIONS: Dopamine agonists probably reduce the incidence of moderate or severe OHSS compared to placebo/no intervention, while we are uncertain of the effect on adverse events and pregnancy outcomes (live birth, clinical pregnancy, miscarriage). Dopamine agonists plus co-intervention may decrease moderate or severe OHSS rates compared to co-intervention only, but we are uncertain whether dopamine agonists affect pregnancy outcomes. When compared to other active interventions, we are uncertain of the effects of dopamine agonists on moderate or severe OHSS and pregnancy outcomes.

[Patent Traditional Chinese Medicine for idiopathic male infertility: A bibliometrical study].

OBJECTIVE: To survey the current status of clinical studies on patent Traditional Chinese Medicine (TCM) for idiopathic male infertility in China. METHODS: Using the keywords "oligospermia", "azoospermia", "asthenozoospermia", "infertility" and "sperm", we searched China National Knowledge Internet (CNKI), Wanfang Database and SinoMed for randomized clinical trials (RCT), cohort studies, case-control studies and case series studies focusing on the treatment of male idiopathic infertility using TCM from January 2001 to May 2017. Two individual reviewers screened the literature, extracted the information separately, recorded the titles, authors, related institutions and regions, journals and years of publication, medication studied, and outcomes. The collected data was analyzed using Microsoft Excel and SPSS. RESULTS: Totally, 307 publications were included in this study, including 243 RCTs (79%), 57 case series studies (19%) and 7 retrospective cohort studies (2%). Fifty one patent TCM and in 146 journals were involved. The number of publications gradully increased from 2001 to 2017. The authors were from 243 institutions in 29 provinces, independent municipalities or autonomous regions, mostly in Guangdong, Guangxi, Henan, Beijing and Jiangsu. Majority of the studies focused on the evaluation of the efficacy and safety of the drugs, among which the most studied medication Wuziyanzong Pills (114/307, 37.13%), Fufangxuanju Capsules, Shengjing Capsules, Huangjingzanyu Capsules, and Liuweidihuang Pills. Chinese Journal of Andrology had the highest number of publications. CONCLUSIONS: A rapid progress has been achieved in China in the studies of patent TCM for the treatment of male infertility. However, limitatiors stiu exist, ragarding inbalance among regions, low sample sizes, low quality of studies, poor involvement of phamacisis.

Therapeutic drug monitoring of vancomycin: a guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

BACKGROUND: Guideline development should be based on the quality of evidence, balance of benefits and harms, economic evaluation and patients' views and preferences. Therefore, these factors were considered in the development of a new guideline for therapeutic drug monitoring (TDM) of vancomycin. OBJECTIVES: To develop an evidence-based guideline for vancomycin TDM and to promote standardized vancomycin TDM in clinical practice in China. METHODS: We referred to the WHO Handbook for Guideline Development and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to rate the quality of evidence and grade the strength of recommendations, according to economic evaluation and patients' views and preferences. We used the GRADE Grid method to formulate the recommendations. RESULTS: The guideline presents recommendations about who should receive vancomycin TDM, how to monitor vancomycin efficacy and renal safety, therapeutic trough concentrations, time to start initial vancomycin TDM, loading dose and how to administer and adjust the vancomycin dose. CONCLUSIONS: We developed an evidence-based guideline for vancomycin TDM, which provides recommendations for clinicians and pharmacists to conduct vancomycin TDM in China.

Dopamine agonists for preventing ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. The dopamine agonist cabergoline was introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment. As cabergoline seemed to be effective in preventing OHSS, other types of dopamine agonists, such as quinagolide and bromocriptine, have since been studied in ART to prevent OHSS. OBJECTIVES: To assess the effectiveness and safety of dopamine agonists in preventing OHSS in high-risk women undergoing ART treatment. SEARCH METHODS: We searched several databases from inception to August 2016 (Cochrane Gynaecology and Fertility Specialised Register of trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, PsycINFO, Clinicaltrials.gov and the World Health Organization International Trials Registry Platform (ICTRP)) for randomised controlled trials (RCTs) assessing the effect of dopamine agonist in preventing OHSS. We handsearched the reference lists of relevant studies. SELECTION CRITERIA: We considered RCTs which compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in high-risk women for inclusion. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary endpoints were clinical pregnancy rate, multiple pregnancy rate, miscarriage rate and any other adverse effects of the treatment. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles, abstracts and full texts of publications, selected studies, extracted data and assessed risk of bias. We resolved any disagreements by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (95% CI) by the Mantel-Haenszel method. In addition, we graded the overall quality of the evidence using GRADE criteria. MAIN RESULTS: The search identified 14 new RCTs since the last published version of this review, resulting in 16 included RCTs involving 2091 high-risk women for this updated review. They evaluated three types of dopamine agonists: cabergoline, quinagolide and bromocriptine.When compared with placebo or no intervention, dopamine agonists seemed effective in the prevention of moderate or severe OHSS (OR 0.27, 95% CI 0.19 to 0.39; 1022 participants; 8 studies; I2 = 0%; moderate quality evidence). This suggests that if 29% of women undergoing ART experience moderate or severe OHSS, the use of dopamine agonists will lower this to 7% to 14% of women. There was no evidence of a difference in live birth rate, clinical pregnancy rate, multiple pregnancy rate or miscarriage rate (very low to moderate quality evidence). However, taking dopamine agonists (especially quinagolide) may increase the incidence of adverse events such as gastrointestinal adverse effects (OR 4.54, 95% CI 1.49 to 13.84; 264 participants; 2 studies; I2 = 49%, very low quality evidence).When we compared dopamine agonist plus co-intervention with co-intervention, there was no evidence of a difference in the outcomes of moderate or severe OHSS, live birth rate, clinical pregnancy rate, miscarriage rate or adverse events. The co-interventions were hydroxyethyl starch (two RCTs) and albumin (one RCT).Cabergoline was associated with a lower risk of moderate or severe OHSS compared with human albumin (OR 0.21, 95% CI 0.12 to 0.38; 296 participants; 3 studies; I2 = 72%). However, there was no evidence of a difference between cabergoline and hydroxyethyl starch, coasting (withholding any more ovarian stimulation for a few days) or prednisolone. There was an increased clinical pregnancy rate in the cabergoline group when cabergoline was compared with coasting (OR 2.65, 95% CI 1.13 to 6.21; 120 participants; 2 studies; I2 = 0%). In other respects, there was no evidence of a difference in clinical pregnancy rate, multiple pregnancy rate or miscarriage rate between cabergoline and other active interventions.The quality of the evidence between dopamine agonist and placebo or no intervention ranged from very low to moderate, mainly due to poor reporting of study methods (mostly a lack of details on randomisation or blinding) and serious imprecision for some comparisons. AUTHORS' CONCLUSIONS: Dopamine agonists appear to reduce the incidence of moderate or severe OHSS in women at high risk of OHSS (moderate quality evidence). If a fresh embryo transfer is performed, the use of dopamine agonists does not affect the pregnancy outcome (live birth rate, clinical pregnancy rate and miscarriage rate) (very low to moderate quality evidence). However, dopamine agonists might increase the risk of adverse events, such as gastrointestinal symptoms. Further research should focus on dose-finding, comparisons with other effective treatments and consideration of combination treatments. Therefore, large, well-designed and well-executed RCTs that involve more clinical endpoints (e.g., live birth rate) are necessary to further evaluate the role of dopamine agonists in OHSS prevention.

[Pharmaceutical care of serious bleeding induced by tramadol-warfarin interaction: a case report].

Warfarin is a high-alert medication, which may result in bleeding if used improperly. In our case, one elderly female with atrial fibrillation had taken warfarin for more than half a year, and her international normalized ratio (INR) was maintained within the therapeutic range. The patient began to take tramadol to alleviate her shoulder pain. Three days later she presented hematuresis and had ecchymosis in her right upper arm, and in the meantime her INR rose to 10.04. Clinical pharmacists analyzed the cause for bleeding by searching relevant literature, and finally discovered the interaction between warfarin and tramadol. On the basis of that, the clinical pharmacists provided pharmaceutical care, offered specific medication education, as well as assisted the physicians to establish the medication plan for warfarin reuse. Eventually, her INR declined to reference ranges, and her hematuresis and ecchymosis were alleviated significantly. This successful case reveals that clinical pharmacy services contribute to better treatment outcomes. Clinical pharmacists can play an active role in anticoagulation management in healthcare team.

Tetrandrine alleviates oxaliplatin-induced mechanical allodynia via modulation of inflammation-related genes.

Oxaliplatin, a platinum-based chemotherapy drug, causes neuropathic pain, yet effective pharmacological treatments are lacking. Previously, we showed that tetrandrine (TET), with anti-inflammatory properties, reduces mechanical allodynia in nerve-injured mice. This study explores the effect of TET on oxaliplatin-induced mechanical allodynia and gene changes in mice. Male C57BL/6J mice received oxaliplatin intraperitoneally to induce mechanical allodynia. Post-treatment with TET or vehicle, the mechanical withdrawal threshold (WMT) was assessed using von Frey filaments. TET alleviated oxaliplatin-induced mechanical allodynia. RNA sequencing identified 365 differentially expressed genes (DEGs) in the Control vs. Oxaliplatin group and 229 DEGs in the Oxaliplatin vs. TET group. Pearson correlation analysis of co-regulated DEGs and inflammation-related genes (IRGs) revealed 104 co-regulated inflammation-related genes (Co-IRGs) (|cor| > 0.8, P < 0.01). The top 30 genes in the PPI network were identified. Arg2, Cxcl12, H2-Q6, Kdr, and Nfkbia were highlighted based on ROC analysis. Subsequently, Arg2, Cxcl12, Kdr, and Nfkbia were further verified by qRCR. Immune infiltration analysis indicated increased follicular CD4 T cell infiltration in oxaliplatin-treated mice, reduced by TET. Molecular docking showed strong binding affinity between TET and proteins encoded by Arg2, Cxcl12, Kdr, and Nfkbia. In summary, TET may alleviate oxaliplatin-induced peripheral neuropathy in clinical conditions.

Tetrandrine attenuates SNI-induced mechanical allodynia by inhibiting spinal CKLF1.

Neuropathic pain (NP) is a prevalent clinical problem for which satisfactory treatment options are unavailable. Tetrandrine (TET), a bisbenzylisoquinoline alkaloid extracted from Stephania tetrandra S. Moore, possesses anti-inflammatory and immune-modulatory properties. Chemokine-like factor 1 (CKLF1) is known to play a crucial role in both peripheral and central inflammatory processes. This study aimed to investigate the potential anti-NP effects of TET and the involvement of CKLF1 in the action of TET. A male C57BL/6J mice model of NP caused by spared nerve injury (SNI) was established and mechanical withdrawal thresholds were measured using von Frey filaments. The results showed that TET improved mechanical allodynia in SNI mice and the propofol-induced sleep assay demonstrated that the TET group did not exhibit central inhibition, while the pregabalin (PGB) group showed significant central inhibition. Western blotting and immunofluorescence staining showed that TET significantly inhibited spinal protein expression levels of CKLF1, p-NF-κB/NF-κB, p-IKK/IKK, pro-inflammatory cytokines IL-1ß and TNF-α, and increased protein expression levels of the anti-inflammatory cytokine IL-10, while inhibiting the expression levels of microglia and astrocyte markers IBA-1 and GFAP of SNI mice. Moreover, immunofluorescence double-labeling results revealed that CKLF1 was predominantly colocalized with microglia of the spinal cord (SC) in SNI mice. C19 (an antagonism peptide of CKLF1) alleviated SNI-induced mechanical pain hypersensitivity, while C27 (an analog peptide of CKLF1) induced mechanical allodynia in normal mice. TET significantly attenuated mechanical allodynia induced by C27 in mice. TET may effectively alleviate NP by reducing neuroinflammation and decreasing CKLF1.

Sotalol permeability in cultured-cell, rat intestine, and PAMPA system.

PURPOSE: To clarify sotalol's classification in the BCS versus BDDCS systems through cellular, rat everted sac and PAMPA permeability studies. METHODS: Studies were carried out in Madin Darby canine kidney (MDCK) and MDR1-transfected MDCK (MDCK-MDR1) cell lines, rat everted gut sacs and the Parallel Artificial Membrane Permeability Assay (PAMPA) system. Three-hour transport studies were conducted in MDCK cell lines (with apical pH changes) and MDCK-MDR1 cells (with and without the P-glycoprotein inhibitor GG918); male Sprague-Dawley rats (300~350 g) were used to prepare everted sacs. In the PAMPA studies, drug solutions at different pH's were dosed in each well and incubated for 5 h. Samples were measured by LC-MS/MS, or liquid scintillation counting and apparent permeability (P(app)) was calculated. RESULTS: Sotalol showed low permeability in all of the cultured-cell lines, everted sacs and PAMPA systems. It might be a border line P-glycoprotein substrate. The PAMPA study showed that sotalol's permeability increased with a higher apical pH, while much less change was found in MDCK cells. CONCLUSION: The low permeability rate for sotalol correlates with its Class 3 BDDCS assignment and lack of in vivo metabolism.

Cabergoline for preventing ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a complication resulting from administration of human chorionic gonadotrophin (hCG) in assisted reproduction technology (ART) treatment. Most case are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Recently, the dopamine agonist cabergoline has been introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS who are undergoing ART treatment. OBJECTIVES: To assess the effectiveness and safety of cabergoline in preventing ovarian hyperstimulation syndrome (OHSS) in high-risk women undergoing ART treatment. SEARCH METHODS: Major medical databases (Cochrane Menstrual Disorders and Subfertility Group Specialised Register of trials, CENTRAL (The Cochrane Library), MEDLINE, EMBASE and PsycINFO) were systematically searched for randomised controlled trials (RCTs) assessing the effect of cabergoline in preventing OHSS. Databases were searched up to September 2011. Registers of clinical trials, abstracts of scientific meetings and reference lists of included studies were searched. No language restrictions were applied. SELECTION CRITERIA: RCTs which compared cabergoline with placebo, no treatment or another intervention for preventing OHSS in high-risk women were considered for inclusion. Primary outcome measures included incidence of moderate or severe OHSS and live birth rate. Secondary endpoints were clinical pregnancy rate, multiple pregnancy rate, miscarriage rate and any other adverse effects of the treatment. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles, abstracts and the full text of publications; extracted data; and assessed risk of bias. Any disagreements were resolved by consensus. Pooled results were reported as odds ratio (OR) and 95% confidence interval (95% CI) by the Mantel-Haenszel method. MAIN RESULTS: Only two trials involving 230 women met the inclusion criteria. Both studies had a moderate risk of bias. Oral cabergoline, 0.5 mg daily, was given as an intervention and compared with a matched placebo. A statistically significant reduction in OHSS was observed in the cabergoline treated group (OR 0.40, 95% CI 0.20 to 0.77; 2 RCTs, 230 women) with a number needed to treat (NTT) of 7. There was a statistically significant difference in the incidence of moderate OHSS, favouring cabergoline (OR 0.38, 95% CI 0.19 to 0.78; 2 RCTs, 230 women) but not in severe OHSS (OR 0.77, 95% CI 0.24 to 2.45; 2 RCTs, 230 women). There was no significant difference in the clinical pregnancy rate (OR 0.94, 95% CI 0.56 to 1.59; 2 RCTs, 230 women), miscarriage rate (OR 0.31, 95% CI 0.03 to 3.07; 1 RCT, 163 women) or any other adverse effects of the treatment (OR 2.07, 95% CI 0.56 to 7.70; 1 RCT, 67 women). However, no data on multiple pregnancy rate or live birth rate were reported in either trial. AUTHORS' CONCLUSIONS: Cabergoline appears to reduce the risk of OHSS in high-risk women, especially for moderate OHSS. The use of cabergoline does not affect the pregnancy outcome (clinical pregnancy rate, miscarriage rate), nor is there an increased risk of adverse events. Further research should consider the risk of administering cabergoline and the comparison between cabergoline and established treatments (such as intravenous albumin and coasting). Large, well-designed and well-executed RCTs that involve more clinical endpoints are necessary to further evaluate the role of cabergoline in OHSS prevention.

[Pharmacokinetics of meropenem administered with prolonged infusion time in patients receiving continuous veno-venous hemofiltration].

OBJECTIVE: To demonstrate the pharmacokinetic profile of meropenem when administered by 3-hour infusion in patients undergoing continuous veno-venous hemofiltration (CVVH). METHODS: The study was conducted in 10 patients, who were treated with CVVH. Each subject received meropenem in 3-hour infusion of 500 mg every 6 hours. Blood samples were collected before infusion (0 hour) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6 hours (just before the infusion of the next dose) after the beginning of the fourth infusion. The concentrations of meropenem in plasma were measured by high-performance liquid chromatography method, and mean serum meropenem concentration-time curve was plotted. RESULTS: Peak plasma drug concentrations measured 3 hours post-infusion were (25.05 ± 5.64) mg/L, and trough levels after 6 hours of infusion were (13.03 ± 3.01) mg/L. The area under the plasma concentration-time curve (AUC) was (118.42 ± 26.78) mg x h⁻¹ x L⁻². The elimination half-life (T1/2) was (3.74 ± 0.55) hours. The mean residence time (MRT) was (4.99 ± 0.84) hours. The volume of distribution (Vb) was (22.85 ± 9.85) L and clearance of meropenem (CL) was (4.49 ± 1.32) L/h. The percentage of time that the serum drug concentration was above the minimum inhibitory concentration (MIC) accounting for the interval time of infusion (%T>MIC) was 100% (MIC 8 mg/L) in all the 10 patients. CONCLUSION: Based on these data, we concluded that satisfactory pharmacodynamic parameters could be attained in CVVH patients treated with meropenem by a prolonged infusion time of 3 hours with a dosage of 500 mg for every 6 hours.

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.

Risk of Liver Injury Associated with Intravenous Lipid Emulsions: A Prescription Sequence Symmetry Analysis.

Aims: To determine the risk of liver injury associated with the use of different intravenous lipid emulsions (LEs) in large populations in a real-world setting in China. Methods: A prescription sequence symmetry analysis was performed using data from 2015 Chinese Basic Health Insurance for Urban Employees. Patients newly prescribed both intravenous LEs and hepatic protectors within time windows of 7, 14, 28, 42, and 60 days of each other were included. The washout period was set to one month according to the waiting-time distribution. After adjusting prescribing time trends, we quantify the deviation from symmetry of patients initiating LEs first and those initiating hepatic protectors first, by calculating adjusted sequence ratios (ASRs) and relevant 95% confidence intervals. Analyses were further stratified by age, gender, and different generations of LEs developed. Results: In total, 416, 997, 1,697, 2,072, and 2,342 patients filled their first prescriptions with both drugs within 7, 14, 28, 42, and 60 days, respectively. Significantly increased risks of liver injury were found across all time windows, and the strongest effect was observed in the first 2 weeks [ASR 6.97 (5.77-8.42) ∼ 7.87 (6.04-10.61)] in overall patients. In subgroup analyses, female gender, age more than 60 years, and soybean oil-based and alternative-LEs showed higher ASRs in almost all time windows. Specially, a lower risk for liver injury was observed in the first 14 days following FO-LEs administration (ASR, 3.42; 95% CI, 0.81-14.47), but the risk started to rise in longer time windows. Conclusion: A strong association was found between LEs use and liver injury through prescription sequence symmetry analysis in a real-world setting, which aligns with trial evidence and clinical experience. Differences revealed in the risks of liver injury among various LEs need further evaluation.

Tolerability and effectiveness of (S)-amlodipine compared with racemic amlodipine in hypertension: a systematic review and meta-analysis.

BACKGROUND: Amlodipine is a calcium channel blocker prescribed for the management of angina and hypertension. As a racemic mixture, amlodipine contains (R)- and (S)-amlodipine isomers, but only (S)-amlodipine as the active moiety possesses therapeutic activity. Based on pharmacologic research, it remains uncertain if (S)-amlodipine alone has similar efficacy and fewer associated adverse events (AEs) compared with the racemic mixtures. OBJECTIVE: The aim of this systematic review and meta-analysis was to determine the effectiveness and tolerability of (S)-amlodipine compared with that of racemic amlodipine. METHODS: A systematic literature search was performed using MEDLINE (1966-2009), EMBASE (1966-2009), the Cochrane Central Register of Controlled Trials (issue 3, 2009), the Chinese Biomedical Database (1978-2009), and the China National Knowledge Internet (1980-2009). All randomized controlled trials (RCTs) comparing (S)-amlodipine 2.5 mg and racemic amlodipine 5.0 mg in the treatment of hypertension were included in the review. The outcome measures to be collected were cardiovascular events, systolic blood pressure (SBP), diastolic BP (DBP), and AEs. Quality assessments of clinical trials were conducted using a modified Jadad Scale, with trials being rated as low quality (score 0-3) or high quality (score 4-7). Meta-analysis of the included studies was performed using RevMan software. RESULTS: Of the 229 references identified, 214 were excluded after screening the titles, abstracts, or full texts. Fifteen RCTs were included, of which 13 were in Chinese and 2 in English. Based on the Jadad Scale score, 3 of the RCTs were classified as high quality (score 5 or 6) and the remaining 12 as low quality (score 1-3). None of the trials evaluated cardiovascular events beyond 40 weeks. Meta-analysis of the 15 trials indicated that (S)-amlodipine was not significantly different from racemic amlodipine in the effect on BP. When only high-quality studies were included, after 4 weeks' treatment, the weighted mean difference (WMD) of SBP and DBP decrease (1 study) was -2.84 (95% CI, -6.42 to 0.74) with (S)-amlodipine and -1.71 (95% CI, -3.48 to 0.06) with racemic amlodipine. After 8 weeks' treatment, the WMD of SBP and DBP decrease (2 studies) was -1.13 (95% CI, -5.29 to 3.03) and -1.34 (95% CI, -2.67 to -0.01), respectively. The risk difference (RD) for the number of patients who experienced AEs with (S)-amlodipine and racemic amlodipine was found to be -0.04 (95% CI, -0.06 to -0.02). When all the trials were included, (S)-amlodipine treatment was associated with significantly less edema than racemic amlodipine (RD, -0.02; 95% CI, -0.03 to 0.00); however, when only high-quality studies (2 studies) were included, no difference was found between the 2 groups (RD, 0.01; 95% CI, -0.02 to 0.03). One high-quality study found significant differences in increases in aspartate and alanine aminotransferase activities in the 2 groups (RD, 0.08; 95% CI, 0.01 to 0.05). No significant differences between the 2 groups were found in the incidence of headache (RD, 0.00; 95% CI, -0.02 to 0.01) or flushing (RD, -0.01; 95% CI, -0.02 to 0.00). CONCLUSIONS: The majority of the clinical trials comparing (S)-amlodipine and racemic amlodipine treatment were low quality (12/15 [80%]). According to the limited evidence, there were no significant differences between (S)-amlodipine 2.5 mg and racemic amlodipine 5.0 mg in controlling BP. When all the trials were considered, (S)-amlodipine treatment was associated with significantly less edema than racemic amlodipine; however, when only high-quality trials were included, no significant difference was found. More long-term, high-quality RCTs with cardiovascular events as the primary outcome are needed to compare the safety and efficacy of (S)-amlodipine and racemic amlodipine.

[A meta-analysis of aprepitant for prevention of chemotherapy-induced nausea and vomiting].

OBJECTIVE: To assess the efficacy and safety of aprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) after moderately or highly emetogenic chemotherapy. METHODS: Studies were identified by searching PubMed (1980 to March, 2010), EMbase (1980 to March, 2010), Cochrane Libraries (Issue 2, 2010), CNKI (1980 to March, 2010), CBMdisc (1980 to March, 2010), and WanFang Data (1982 to March, 2010). Randomized controlled trials of aprepitant for the prevention of CINV were included. The quality of included studies was assessed and meta-analysis was performed for the results of homogeneous studies by RevMan 5.0.23 software. RESULTS: Ten studies involving 4 376 oncology patients were included. They were all high quality studies, with Jadad scores more than 5. The results of meta-analysis were as follows: (1) Acute CINV: The overall complete response rate was improved by 14.21% when aprepitant was combined with ondansetron and dexamethasone (83.33% vs 72.96%; P<0.001). Subgroup analysis showed the patients receiving AC (anthracycline/cyclophosphamide) regimen benefited less than the patients receiving cisplatin chemotherapy. The rate of no significant nausea was only improved by 3.92% (P=0.04). (2) Delayed CINV: Compared with ondansetron, aprepitant could improve vomiting by 14.98% (P=0.004). When aprepitant was added with dexamethasone, the response rate of vomiting and nausea was improved by 37.72% (P<0.001) and 11.24% (P=0.008) respectively. (3) Adverse reactions: The incidence of fatigue/asthenia was higher in the aprepitant regimen (P=0.001), while the incidence of constipation was lower (P=0.002). CONCLUSION: Aprepitant can improve the control of vomiting, but has slight effect on nausea. Patients receiving AC regimen benefit less than patients receiving cisplatin chemotherapy. In view of its high cost, pharmacoeconomics researches of aprepitant should be considered.

[A case report of monitoring on carbamazepine in breast feeding woman].

To evaluate the safety of oral cabamazepine during breast milk feeding. The carbamazepine concentration in breast milk of one epilepsy maternal patient was assayed by high performance liquid chromatography, and the literature was reviewed to find the nursing evidence in the use of cabamazepine. The carbamazepine concentration in breast milk ranged from 0.34-0.86 mg/L. The neonate daily dose intake was estimated ranging from 0.34 mg to 0.86 mg through breast-feeding in theory. The literature showed that carbamazepine was generally considered safe for use during breast feeding; however, adverse effects should be monitored as recommended. It is better to avoid feeding at high concentration level to minimize the harm of carbamazepine to the baby.

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.

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.

Cost-effectiveness of Dabigatran Compared With Rivaroxaban for Prevention of Stroke and Systemic Embolism in Patients With Atrial Fibrillation in China.

PURPOSE: In China, dabigatran and rivaroxaban are the only approved non-vitamin K antagonist oral anticoagulants for the treatment of atrial fibrillation (AF). The goal of this article was to assess the cost-effectiveness of dabigatran versus rivaroxaban for the prevention of stroke and systemic embolism in Chinese patients with AF from the perspective of the Chinese health care system. METHODS: A Markov model was constructed to estimate the cost-effectiveness of dabigatran versus rivaroxaban. Clinical events were modeled for a lifetime horizon, based on clinical efficacy data from indirect treatment comparisons. The weighted average of the most recent prices of these 2 drugs was used as the drug acquisition cost. Other costs, including follow-up costs and event costs, were collected by using a survey from a panel of local experts. Utility inputs (health state utilities, clinical event disutilities, and event history utility) were obtained from published literature. Sensitivity analyses that included scenario analyses and a probabilistic sensitivity analysis were conducted to examine the robustness of the economic model. FINDINGS: Over a lifetime, patients treated with dabigatran experienced fewer ischemic strokes (2.14 dabigatran vs 2.61 rivaroxaban) and fewer intracranial hemorrhage (0.48 vs 0.94) per 100 patient-years. In the base case analysis, dabigatran had an incremental cost of ¥28,128 but with higher life years (10.38 vs 10.14) and quality-adjusted life years (QALYs) (7.95 vs 7.70). The resulting incremental cost-effectiveness ratio of ¥112,910 per QALY gained and net monetary benefit of ¥12,214 versus rivaroxaban showed that dabigatran was a cost-effective alternative to rivaroxaban. Extensive sensitivity analyses indicated that the results were robust over a wide range of inputs. The probabilistic sensitivity analysis indicated that dabigatran was cost-effective in 84.2% of the 10,000 Monte Carlo simulations compared with rivaroxaban. IMPLICATIONS: Dabigatran reduced the occurrence of clinical events and increased QALYs compared with rivaroxaban. The use of dabigatran for the prevention of stroke and systemic embolism is a cost-effective option compared with rivaroxaban among patients with AF in China.