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Objective. Programmed cell death-1 (PD-1) inhibitors have shown potency for neoadjuvant therapy in several cancers, while their administration combined with concurrent chemoradiotherapy (CCRT) as a neoadjuvant therapy for locally advanced esophageal squamous-cell carcinoma (ESCC) is seldom reported. The current study aimed to investigate the pathological response, survival, and safety of neoadjuvant PD-1 inhibitor plus CCRT in locally advanced ESCC patients. Methods. Twenty-five locally advanced ESCC patients who underwent PD-1 inhibitor plus CCRT neoadjuvant therapy were retrospectively reviewed. Data regarding radiological response, pathological response, disease-free survival (DFS), overall survival (OS), and adverse events were retrieved. Results. Two (8.0%), 14 (56.0%), 9 (36.0%), and 0 (0.0%) patients had a clinical response of complete response, partial response, stable disease, and progressive disease after neoadjuvant therapy by radiological evaluations, respectively. Notably, 25 (100.0%) patients had successful tumor resections, 24 (96.0%) patients realized R0 resection, and 13 (52.0%) patients achieved pathological complete response (pCR) by pathological evaluations. Regarding survival profiles, the 1-year and 2-year accumulating DFS rates were 90.0% and 74.6%, respectively; then, the 1-year and 2-year accumulating OS rates were 95.5% and 90.4%, respectively. The top prevalent adverse events were fatigue (48.0%), nausea and vomiting (40.0%), leukopenia (36.0%), neutropenia (36.0%), and peripheral neuropathy (36.0%). In addition, grades 3-4 adverse events included peripheral neuropathy (12.0%), nausea and vomiting (4.0%), leukopenia (4.0%), neutropenia (4.0%), anemia (4.0%), and pruritus (4.0%). Conclusion. Neoadjuvant PD-1 inhibitor plus CCRT shows a good efficacy and acceptable tolerance for locally advanced ESCC treatment, but further large-scale study validation is needed. [ABSTRACT FROM AUTHOR]

Purpose. Hypertension (HTN) is one of the most common adverse drug reactions to tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF), but little is known about its clinical risk factors. The aim of this study was to elucidate the association between baseline clinical characteristics and the occurrence of HTN in advanced gastric cancer (GC) patients prescribed apatinib, a commonly used VEGF-TKI in China, in a real-world setting. Patients and Methods. Fifty-five GC patients treated with apatinib from December 1st, 2016, to December 1st, 2020, were retrospectively included in electronic medical records. Adverse drug reactions were defined according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Univariate and multivariable logistic regression analyses were used to investigate potential clinical risk factors for apatinib-related HTN. Results. The incidence of apatinib-related HTN of all grades was 45.45%, and grade 3 HTN occurred in 16.36% of patients. The median maximal systolic blood pressure (SBP) during apatinib treatment was 153 mm·Hg, and the median time to event was 25 days. New-onset HTN occurred in 10/33 (30.30%) patients. Preexisting HTN (odds ratio [OR]: 4.155; 95% confidence interval [CI]: 1.252, 13.787; p = 0.020) was the key independent risk factor associated with apatinib-related HTN. Conclusion. The incidence of HTN was high in patients treated with apatinib, and preexisting HTN was an independent risk factor. It is important to provide thorough and close monitoring of patients during treatment with apatinib, especially for those with preexisting HTN. This trial is registered with ChiCTR1900024531. [ABSTRACT FROM AUTHOR]

Background. NUDT15 gene polymorphisms have been identified to predispose Asian patients with an inflammatory bowel disease (IBD) to thiopurine-induced leukopenia. This study predicted the influence of NUDT15 haplotypes and diplotypes on azathioprine (AZA)-induced leukopenia as well as the long-term influence of AZA on hematologic parameters in IBD. Methods. 194 IBD patients were tested for NUDT15 genotypes. We collected clinical data of 80 patients with AZA treatment including adverse events, dosage, white blood cell (WBC) count, platelet (PLT) count, and mean corpuscular volume (MCV) after AZA initiation. Patients without adverse events and drug withdrawal were followed up for at least one year. The relationship between NUDT15 haplotypes and diplotypes and leukopenia was analyzed. Results. The haplotypes NUDT15 c.415C > T and c.36_37insGGAGTC as well as the diplotypes NUDT15 ∗ 1/ ∗ 2, ∗ 3/ ∗ 3, and ∗ 3/ ∗ 5 were significantly associated with AZA-induced leukopenia. Only one patient with NUDT15 c.52G > A experienced leukopenia. NUDT15 ∗ 1/ ∗ 3 was not associated with leukopenia. After AZA initiation, the WBC count showed a downward trend in both wild types and mutants. The mean of WBC count in the mutant group at 1st month after AZA initiation was lower than that in the wild-type group (P = 0.006). The MCV increased gradually in mutant cases (P = 0.039), and the differences were obvious at 6th and 12th months compared with the baseline (P = 0.014 a n d P = 0.042 , respectively). The PLT count showed a decreasing trend in the mutant group, but there was no difference until 11 months after initiating treatment (P = 0.023). The final dose of AZA in the NUDT15 mutant group was significantly lower than that in the wild-type group (P = 0.006). Conclusion. NUDT15 polymorphisms may be an appropriate predictor of AZA abnormal hematologic indices in IBD patients. It is necessary for IBD patients to monitor hematological indices and optimize AZA therapy. [ABSTRACT FROM AUTHOR]

What Is Known and Objective: Only a few studies about polymyxin B (PMB) against multidrug‐resistant gram‐negative bacteria (MDR GNB) infection were conducted in liver transplantation recipients (LTRs). The purpose of this study was to investigate the efficacy and safety of PMB in the treatment of MDR‐GNB in liver transplant recipients and to determine the risk factors affecting clinical cure and 30‐day all‐cause mortality. Methods: Data of LTRs receiving PMB from January 2016 to February 2020 were collected. Clinical cure and 30‐day all‐cause mortality were the main efficacy outcomes, while the incidence of nephrotoxicity, neurotoxicity, and hyperpigmentation of PMB was the main safety outcome. Results and Discussion: Data of 42 LTRs were included. Clinical cure with PMB was observed in 27 recipients (64.3%), and the 30‐day all‐cause mortality rate was 31.0% (13/42). The incidence of acute kidney injury (AKI), neurotoxicity, and hyperpigmentation was 57.1% (16/28), 4.8% (2/42), and 16.7% (7/42), respectively. Logistic regression analysis showed that Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR, 1.203; 95% CI, 1.016–1.423, p = 0.032) was an independent risk factor for 30‐day all‐cause mortality, whereas renal replacement therapy (OR, 0.128; 95% CI, 0.019–0.860, p = 0.034) was an independent risk factor for clinical cure with PMB. What Is New and Conclusions: This is the first study to evaluate the application of PMB in LTRs. If there were no better therapeutic options left for LTRs other than PMB, it can be used against MDR GNB infection in LTRs. We should closely observe adverse events or reactions, and adjust the dose based on the balance of efficacy and safety. [ABSTRACT FROM AUTHOR]

What Is Known and Objective: Hypertension (HP) is associated with heart failure (HF). Sacubitril/valsartan (sac/val) has been approved for primary HP by China Food and Drug Administration (CFDA) in June 2021. The present study aimed to provide evidence on the effectiveness and safety of sac/val in Chinese patients complicated with HP and HF. Methods: This retrospective study was conducted on adult patients diagnosed with HP and HF and treated with sac/val between July 2020 and December 2020. The potential risk factors for the discontinuation events caused by sac/val‐related adverse events (AEs) were explored. The data, including blood pressure (BP), cardiac indicators, corresponding values on echocardiographic parameters, unplanned visits, and AEs throughout 3–12 months, were collected. Results and Discussion: A total of 446 eligible patients were included in this study. The discontinuation events of sac/val were mainly attributed to its AEs (hypotension, hyperkalemia, and deterioration in kidney function). Univariate analysis revealed that history of chronic kidney disease, atrial fibrillation, higher values of serum creatinine, serum uric acid, serum N‐terminal pro B‐type natriuretic peptide, and lower estimated glomerular filtration rate were potential risk factors for discontinuation. Patients who maintained sac/val therapy throughout 3–12 months showed significantly improved values of clinical BP, cardiac indicators, and echocardiographic parameters compared to those at baseline (p < 0.0001). What Is New and Conclusion: Sac/val was effective on BP and improved cardiac function in patients complicated with HP and HF. The physicians should focus on patients with renal dysfunction to take timely precautions to improve tolerability for sac/val. [ABSTRACT FROM AUTHOR]

What is known and objective: MTX pharmacology and toxicity involve several metabolizing enzymes and transporters whose functions have been suggested to be altered by genetic polymorphisms. The current study is to investigate the relationship between the genetic variation and MTX‐induced adverse drug effects. Methods: A total of 80 paediatric patients (aged 1–14 years) were enrolled in this study. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 scoring system. Genotyping was performed by MassARRAY Assay method. Data were analysed using Spss statistical package version 17.0 and Plink v1.07 software. The HWE was tested by a chi‐square test. The Fisher's exact test (chi‐squaretest) was used to compare the distributions of genotypes between cases and controls. OR and 95%CI were applied to evaluate the association of genetic variants with the presence of mucositis using unconditional logistic regression. Results and discussion: Mucosal inflammatory injuries were found in 28 children. SNPs of rs1128503 (p = 0.0022, OR = 3.04, 95%CI = 1.39–6.64) and rs1045642 (p = 0.0052, OR = 2.38, 95%CI = 1.15–5.00) located in the gene of ABCB1 and SNPs of rs1801133 (p = 0.040, OR = 2.50, 95%CI = 1.06–5.88) located in the gene of MTHFR show marked impacts on the risk of developing mucositis. What is new and conclusion: SNPs of ABCB1 rs1128503, rs1045642 and MTHFR rs1801133 can be risk predictor for MTX‐induced mucositis in Chinese paediatric patients diagnosed with acute lymphoblastic leukaemia, lymphoma or osteosarcoma. [ABSTRACT FROM AUTHOR]

What is known and objective: The primary adverse reaction of linezolid is haematological toxicity, leading to thrombocytopenia and anaemia. This study aimed to investigate the risk factors of linezolid‐induced anaemia (LI‐AN) and establish a predictive model by multivariate logistic regression model analysis to predict LI‐AN risks in Chinese adult patients. Methods: Demographic and clinical data of patients who underwent linezolid therapy for more than three days between January 2014 and December 2020 in Zhongshan Hospital, Fudan University, were retrieved from the hospital's electronic medical record for analysis. Multivariate logistic regression analysis was employed to establish a predictive model, whose predictability was further evaluated by the area under the receiver operating characteristic (ROC) curve. Results and discussion: The study comprised 298 patients among the 2322 patients who underwent linezolid treatment between 2014 and 2020. Among the 298 patients, 32 (10.7%) developed anaemia with an average of 11.4 (SD 6.2) days after the initiation of linezolid therapy. Multivariate logistic analysis revealed that age ≥60 years (odds ratio [OR] 2.815, 95% confidence interval [CI] 1.242–6.379), higher total bilirubin (TBi) (OR 1.031, 95% CI 1.011–1.051), eGFR < 60 ml/(min·1.73 m2) (OR 2.537, 95% CI 1.054–6.106), duration of linezolid therapy (DLT) (OR 1.091, 95% CI 1.023–1.163) and intensive care unit (ICU) admittance (OR 2.664, 95% CI 1.150–6.174) were the independent risk factors for anaemia occurrence among patients receiving linezolid therapy. A logistic regression equation based on the five risk factors was subsequently established and transformed to obtain the calculation formula of the combined predictor: Y(Combined predictor) = XTBi + 34.5 × XAge≥60 + 31.1 × XeGFR<60 + 32.7 × XICU + 2.9 × XDLT, (where Age ≥60 years, yes = 1, no = 0; eGFR < 60 ml/(min·1.73 m2), yes = 1, no = 0; ICU admittance, yes = 1, no = 0). The area under the ROC curve of the combined predictors equation was 0.773 with an optimal cut‐off point value of 92.4, corresponding to a 75.0% sensitivity and 76.7% specificity. What is new and conclusion: LI‐AN is associated with age (≥60 years), higher TBi, eGFR < 60 ml/(min·1.73 m2), DLT and ICU admittance. Physicians should thus calculate the combined predictor value at the beginning of linezolid treatment to predict and evaluate the risk of LI‐AN. An optimal cut‐off value larger than 92.4 indicates that the patient has a higher LI‐AN risk. As such, Hb levels should be monitored regularly, and dosage regimens adjusted accordingly to prevent anaemia occurrence. This study provides an evidence‐based logistic model that reduces LI‐AN incidences and promotes the safe clinical use of linezolid. [ABSTRACT FROM AUTHOR]

What is known and objective: Vancomycin therapeutic guidelines suggest a loading dose of 25‐30 mg/kg for seriously ill patients. However, high‐quality data to guide the use of loading doses are lacking. We aimed to evaluate whether a loading dose (a) achieved a target trough concentration at steady state and (b) improved early clinical response. Methods: Patients with an estimated glomerular filtration rate ≥ 90 mL/min/1.73 m2 were included. A loading dose of 25 mg/kg vancomycin followed by 15 mg/kg twice daily was compared with traditional dosing. A Cmin sample was obtained before the fifth dose. An early clinical response 48‐72 hours after the start of therapy and clinical success at end of therapy (EOT) was evaluated in patients with methicillin‐resistant Staphylococcus aureus (MRSA), methicillin‐resistant coagulase‐negative Staphylococci or Enterococcus faecium. Results: There was no significant difference in Cmin between the regimen with and without a loading dose (median: 10.4 and 10.2 µg/mL, P =.54). Proportions of patients achieving 10‐20 and 15‐20 µg/mL were 56.9% and 5.6%, respectively, in patients with a loading dose. Although there was no significant difference in success rate at EOT between groups, a loading dose was associated with increased early clinical response for all infections (adjusted odds ratio [OR]: 4.588, 95% confidence interval [CI]: 1.373‐15.330) and MRSA infections (OR: 12.065, 95% CI: 1.821‐79.959). Study limitations included no Cmin measurements within 24 hours and the inclusion of less critically ill patients. What is new and conclusion: A loading dose of 25 mg/kg followed by 15 mg/kg twice daily did not achieve the optimal Cmin at steady state in patients with normal renal function. However, more early clinical responses were obtained with a loading dose compared with traditional dosing, possibly because of a prompt albeit temporary achievement of a more effective concentration. [ABSTRACT FROM AUTHOR]

What is known and objective: With the ageing of the population also comes increasing comorbidities and the use of multiple medications and administration methods, along with greater susceptibility to adverse drug reactions. Dosage form modification to facilitate drug administration in older adults can be potentially problematic as altering the original licensed formulation can affect medication safety and efficacy. The reporting of adverse drug reactions and medication incidents is a key strategy in avoiding preventable adverse drug events for aged care residents. This study evaluated the effect of an on‐site clinical pharmacist on reducing inappropriate dosage form modification and staff time spent on medication administration, and optimizing the documentation of drug allergies, adverse drug reactions and medication incidents. Methods: A pilot‐controlled trial was performed in a purposive sample of two residential aged care homes. Both homes belonged to the same organization; the study site had 104 beds and the control site had 100 beds. All permanent residents were eligible for inclusion in the study if written consent was provided. A residential care pharmacist position was implemented at the study site for six months, with a focus on performing medication reviews and quality improvement activities. Observational audits of medication rounds were performed, and documentation relating to allergies, adverse drug reactions, and medication incidents was obtained from both sites before and after the pharmacist trial period. Results: At the study site, there was a significant reduction over the trial in the proportion of inappropriate dosage form modification (from 24% to 0% of all dosage form modifications; P < 0.01). Mean time spent on medication rounds per resident reduced from 4.8 minutes per resident (SD 1.1) to 3.2 minutes per resident (SD 1.7) per round (P < 0.05). The incidence of previous allergy and adverse drug reaction documentation significantly improved from 77% of residents pre‐study to 100% of residents post‐study (P < 0.01). Mean monthly medication incident reports significantly improved from 13.3 (SD 7.4) pre‐study to 25.7 (SD 10.8) post‐study (P < 0.05). There was no change in these outcomes at the control site. What is new and conclusion: Including a pharmacist in a residential aged care home can improve medication administration practices by reducing inappropriate dosage form modification and staff time spent on medication administration rounds, and increasing the documentation of resident allergies, adverse drug reactions and medication incidents. These findings warrant further exploration in a large randomized controlled trial. [ABSTRACT FROM AUTHOR]

What is known and objective Current treatments for depressive disorders are far from optimum. This study was planned to evaluate possible antidepressant effects and safety of memantine, a selective N-methyl- d-aspartate receptor antagonist, in humans. Methods Sixty-six outpatients with the diagnosis of moderate-to-severe major depressive disorder, based on DSM-V diagnostic criteria, were recruited to participate in a parallel, randomized, controlled trial. Sixty-two participants completed 6 weeks of treatment with either memantine (20 mg/day) plus sertraline (200 mg/day) or placebo plus sertraline (200 mg/day). Patients were evaluated using the Hamilton Depression Rating Scale ( HDRS) at baseline and at weeks 2, 4 and 6. Comparison of treatment efficacy in improving depressive symptoms between the two groups was the principal outcome measure. Results and discussion A repeated-measures analysis demonstrated significant time × treatment interaction on HDRS score [F (2·09, 125·67) = 5·09, P = 0·007]. Significantly greater improvement was seen at all three follow-up sessions as well as significantly greater response rates at weeks 4 and 6 ( P = 0·018 and P < 0·001, respectively) in the memantine group. Significantly more early improvers and more rapid response to treatment were observed in the memantine group ( P = 0·001 and P < 0·001, respectively). A significant reduction was observed in HDRS score from baseline to the study endpoint in both memantine ( P < 0·001, Cohen's d = 12·71) and placebo groups ( P < 0·001, Cohen's d = 5·13). No serious adverse event occurred. No significantly greater remission rate was seen in the adjunctive memantine therapy. What is new and conclusion A 6-week course of treatment with memantine as adjunct to sertraline showed a favourable safety and efficacy profile in patients with major depressive disorder. Nonetheless, larger controlled studies of longer duration are necessary to assess long-term safety, efficacy and optimal dosing. [ABSTRACT FROM AUTHOR]

What is known and objective Various factors contribute to the high rate of readmission among patients hospitalized with heart failure ( HF). Determination of these factors is fundamental to identify potential targets for intervention in hospitalized patients. Methods The retrospective cohort study used a large national insurance database to identify episodes of HF. Clinical information up to 12 months from the index hospitalization was obtained. Depending on their outcome, eligible patients were classified into a 30-day readmission group after discharge or a non-readmission group. Potential predictors of 30-day readmission were categorized by patient, drug therapy and health system utilization factors. Results and discussion Heart failure was identified in 19 128 inpatients. Of these, 27·6% were readmitted within 30 days after discharge. The mean Charlson comorbidity index ( CCI) score was 5·2 ± 2·9 for the readmission group and 4·3 ± 2·5 for the non-readmission group. The strongest predictors included paralysis [adjusted odds ratio ( AOR) 2·27, 95% confidence interval ( CI) 1·97-2·62], followed by metastatic cancer ( AOR 2·22, 95% CI 1·81-2·72) and loop diuretic therapy ( AOR 1·52, 95% CI 1·29-1·79). A prescription of ACE inhibitor or angiotensin receptor blocker at discharge was associated with a 17% decreased risk ( AOR 0·83, 95% CI 0·77-0·89). What is new and conclusions Hospitalized patients with HF have a 30-day all-cause readmission rate exceeding a quarter. Post-discharge care should focus on patients with advanced age, acuity of admission, enrolled medical aid, hospitalization exceeding 14 days, higher CCI score, more than 10 prescription drugs at discharge, presence of several comorbidities and loop diuretic therapy, which are independent predictors for 30-day readmission. [ABSTRACT FROM AUTHOR]

What is known and objective Tacrolimus is a widely used immunosuppressive drug with marked pharmacokinetic variability partly due to CYP3A5 polymorphism. Our study aimed to investigate the dynamic effects of CYP3A5 genotypes on dose requirement and trough concentration ( C0) of tacrolimus in renal transplant recipients. Methods A total of 194 Chinese renal transplant recipients received oral tacrolimus twice daily. Whole-blood C0 of tacrolimus were measured on the 3rd day, 7th day, 14th day, 1st month, 3rd month and 6th month post-transplantation. CYP3A5 genotypes were determined and the recipients were categorized as CYP3A5 expressers ( CYP3A5*1 allele carriers) and non-expressers (homozygous CYP3A5*3). The correlated serum creatinine, haematocrit and albumin were also detected. Results The allele frequencies for CYP3A5*1/*1, *1/*3 and *3/*3 were 7·7%, 44·8% and 47·4%, respectively. There were no significant variability in serum creatinine, haematocrit and albumin values between CYP3A5 expressers and non-expressers. Larger doses were administered to CYP3A5 expressers than to non-expressers after surgery except the initial dose. C0 were much lower in CYP3A5 expressers than in non-expressers on the 3rd day, 7th day, 14th day and 1st month post-transplantation ( P < 0·01); however, no significant differences were found on the 3rd and 6th months post-transplantation. All of the dose-adjusted C0 in CYP3A5 expressers were significantly lower than non-expressers ( P < 0·01). Less of the recipients achieving target C0 (4-8 ng/mL) were found in CYP3A5 expressers than in non-expressers after initial dose (35·7% vs. 50%). Meanwhile, CYP3A5 non-expressers were detected having higher C0 (>8 ng/mL) during 3 months post-transplantation. Besides, the proportions in the two groups both increased gradually over time and up to 91·8% and 94% on the 6th month, respectively. What is new and conclusion There are no significant differences in serum creatinine, haematocrit and albumin values between CYP3A5 expressers and non-expressers. CYP3A5 expressers have decreased dose-adjusted tacrolimus C0 when compared to non-expressers. Dose-adjusted C0 of tacrolimus increases in a time-dependent manner in both groups. [ABSTRACT FROM AUTHOR]

What is known and objective Vancomycin is one of the most widely used antibiotics for treating serious Gram-positive infections in children. Few clinical studies have examined the potential risk factors for treatment failure in children receiving vancomycin. The objectives of this study were to evaluate the relationships between vancomycin trough concentration and treatment outcomes in Chinese paediatric patients with suspected Gram-positive infections and to identify baseline characteristics that may affect treatment failure associated with vancomycin use. Methods A retrospective cohort study was conducted from April 2007 to October 2015. Patients were included in this study if they were <18 years old, had received vancomycin for at least 72 h and had at least one bacterial culture and one serum steady-state vancomycin trough concentration. Treatment outcomes were defined as success or failure. Nephrotoxicity was defined as a serum creatinine (Scr) increase ≥44·2 μmol/L or a ≥50% increase in baseline Scr for at least two consecutive days. Univariate and multivariate logistic regression analyses were performed to identify risk factors for treatment failure with vancomycin. Results and discussion One hundred and eighty-two patients were included. Vancomycin treatment failure occurred in 52 patients (28·6%), and the incidence of nephrotoxicity was low. No significant difference was observed in the vancomycin trough concentrations between the treatment success and failure groups. Multivariate logistic regression analyses showed that the vancomycin trough concentration [odds ratio ( OR), 1·046; 95% confidence interval ( CI), 0·979-1·118; P = 0·179, statistical power: 62·04%)] was not associated with treatment outcome, and only intensive care unit ( ICU) admission ( OR, 3·808; 95% CI, 1·714-8·465; P = 0·001, statistical power: 90·40%) was found to be independently associated with vancomycin treatment failure. What is new and conclusion Our findings suggest that the vancomycin trough concentration is not associated with treatment outcome. ICU admission is an independent predictor of treatment failure. [ABSTRACT FROM AUTHOR]

What is known and objective Dyslipidaemia is the key risk factor for arthrosclerosis, leading to myocardial infarctions and strokes. Achieving LDL cholesterol (LDL-C) treatment goals using lipid-lowering therapy (LLT) mitigates such cardiovascular risks. This study aimed to determine the proportions and factors influencing patients with dyslipidaemia on LLT who achieved their recommended LDL-C treatment goals. Methods Adult Asian patients with dyslipidaemia, aged 31-80 years, were enrolled in a questionnaire survey. Using simplified Framingham risk scores, these patients were classified into low (LR), medium (MR) and high (HR) cardiovascular risk groups. Their lipid-lowering therapy was classified into low-intensity (LI), medium-intensity (MI) and high-intensity (HI) groups according to the 2013 American College of Cardiology and American Heart Association (ACC/AHA) Blood Cholesterol Guidelines. Data on their demographic, clinical, self-reported attitude and adherence to LLT were correlated with their latest lipid profiles from their electronic health records. These data were analysed using chi-square test, or independent t-test where appropriate for categorical variables and continuous data. Logistic regression was used to identify factors relating to LDL-C goal attainment. Results and discussion Amongst the 917 patients treated with LLT, 60·9% were females and 56·2% aged >60 years. The commonest statins prescribed were simvastatin (77·7%), atorvastatin (15·3%), rosuvastatin (4·3%) and lovastatin (3·4%). Those who attained LDL-C treatment goals included 89·4%, 77·4% and 70% of the LR, MR and HR groups. Overall, 72·4% of the patients achieved LDL-C treatment goals. Despite 98·4% of them self-reported LLT adherence, only 85·5%, 69·5% and 50% of the LI, MI and HI subgroups attained the desired outcomes, respectively. What is new and conclusion Overall, 27·6% of patients with dyslipidaemia, including 30% of the HR group, did not achieve LDL-C treatment goals, despite on LLT. Addressing their concerns and adjusting medication doses of their LLT are needed for better outcomes. [ABSTRACT FROM AUTHOR]

What is known and objective The correct management of high-alert medications is a priority issue in expert recommendations for improving the clinical safety of patients. Objectives were to assess the impact of the implementation of vasoactive drug ( VAD) protocols on safety and efficacy in the treatment of critically ill patients. Methods A prospective before-and-after study on the implementation of different VAD protocols, comparing medication errors ( MEs) rates, mean intensive care unit ( ICU) stay, mean blood pressure ( MAP), heart rate ( HR) and oxygen saturation. Results and discussion The study included 432 patients. There was a statistically significant decrease in prescribing errors (55·9%), validation errors (68·1%) and medication administration records ( MAR) errors (78·8%). No differences were found between the two phases in ICU stay, MAP, HR and oxygen saturation. What is new and conclusion Implementation of protocols decreases variability in clinical practice, reduces the incidence of MEs and maintains the effectiveness of VAD therapy in critically ill patients. [ABSTRACT FROM AUTHOR]

What is known and objective Patients admitted to general medical units and emergency short-stay units are often complex with multiple comorbidities, polypharmacy and at risk for drug-related problems associated with increased morbidity and mortality. The aim of this study was to evaluate the effectiveness of a partnered pharmacist charting model completed at the time of admission to prevent medication errors. Methods We conducted an unblinded cluster randomized controlled trial comparing partnered pharmacist charting to standard medical charting among patients admitted to general medical units and emergency short-stay units with complex medication regimens or polypharmacy. This trial was conducted at an adult major referral hospital in metropolitan Melbourne, Australia, with an annual emergency department attendance of approximately 60 000 patients. The evaluation included patients' medication charts written in the period of 16 March 2015 to 27 July 2015. Patients randomized to the intervention were managed using the partnered pharmacist charting model. The primary outcome variable was a medication error identified by an independent assessor within 24 h of admission, who was not part of the patient's admission process. Results Of the 473 patients who received standard medical staff charting during the study period, 372 (78·7%) had at least one medication error identified compared to 15 patients (3·7%) on the partnered pharmacist charting arm ( P < 0·001). The relative risk of an error with standard medical charting was 21·4 (95% CI: 13·0-35·0) with a number needed to treat ( NNT) to prevent one error of 1·3 (95% CI: 1·3-1·4), and the relative risk of a high or extreme risk error with standard medical charting was 150·9 (95% CI: 21·2-1072·9) with a NNT to prevent one high or extreme error of 2·7 (95% CI 2·4-3·1). What is new and conclusion Partnering between medical staff and pharmacists to jointly chart initial medications on admission significantly reduced inpatient medication errors (including errors of high and extreme risk) among general medical and emergency short-stay patients with complex medication regimens or polypharmacy. [ABSTRACT FROM AUTHOR]

What is known and objective Antibiotic therapy aimed at eradicating Pseudomonas aeruginosa ( Pa), and improved regimens to treat chronic Pa infection have played a major role in increasing the median survival of patients with cystic fibrosis ( CF). However, different clinical centres use varying eradication regimens. The aim of this study was to evaluate the efficacy of multiple eradication treatments against initial Pa infection and to determine the factors affecting the treatment success. Methods This study was conducted at the Hacettepe University Department of Pediatric Pulmonology. We examined the demographic, clinical and microbiological data of 146 CF patients with first Pa isolation in sputum culture from all 630 patients with CF studied. We aimed to identify the factors that affected the eradication of Pa infection and assessed the success rates of the different eradication protocols used. Results and discussion The mean age of the patients was 71·5 months (2 months-29 years) when Pa was first isolated; the mean duration from CF diagnosis to first Pa isolation was 40 months. The most common treatment choices consisted of 2 weeks of intravenous ceftazidim-amikacin for severe exacerbation or 3 months of inhaled gentamycin combined with 3 weeks of oral ciprofloxacin for mild exacerbation in asymptomatic patients. With these treatment regimens, eradication was observed in 47 patients (32%), intermittent colonization in 42 patients (28%) and chronic colonization in 57 patients (40%). Forced expiratory volume in 1 s decline was statistically significant in patients with chronic colonization ( P = 0·006). Being older than 2 years of age or having symptoms at the first Pa isolation was negatively associated with the treatment success. What is new and conclusion Early antibiotic treatment for Pa can eradicate the bacteria, prevent or delay the development of chronic colonization and improve the general health status. The acquisition of Pa at an older age and having symptoms at first isolation negatively affected the success of eradication. The use of intravenous antibiotics may increase the efficacy of therapy. Inhaled tobramycin for Pa eradication was approved for reimbursement in Turkey from August 2014. The relatively low eradication rate may be explained by a lack of reimbursement for inhaled tobramycin and colistin in our country during the study period. [ABSTRACT FROM AUTHOR]

What is known and objective: N-acetylcysteine (NAC) has been proposed as a potential therapy for obsessive-compulsive disorder (OCD) as it may regulate the exchange of glutamate and prevent its pre-oxidant effects. The aim of the present double-blind, placebo-controlled trial was to assess the efficacy and tolerability of NAC augmentation in moderate-to-severe (OCD) treatment. Methods: In this randomized, double-blind, two-centre, placebo-controlled, 10-week trial, patients with moderate-to-severe OCD were enrolled. Patients were randomized into two parallel groups to receive fluvoxamine (200 mg daily) plus placebo or fluvoxamine (200 mg daily) plus NAC (2000 mg daily). A total of 44 patients (22 in each group) were visited to evaluate response to therapy using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) at baseline, and at weeks 4, 8 and 10. Side effects were recorded using predesigned checklists upon each visit. Results and discussion: Repeated-measures ANOVA showed a significant effect for time × treatment interaction (Greenhouse-Geisser corrected: F = 5.14, d.f. = 1.64, P = 0.012) in the Y-BOCS total score and a significant effect for time × treatment interaction (Greenhouse-Geisser corrected: F = 5.44, d.f. = 1.54, P = 0.011) in the Y-BOCS obsession subscale between the two groups. What is new and conclusion: Our results showed that NAC might be effective as an augmentative agent in the treatment of moderate-to-severe OCD. Trial registration: Iranian Registry of Clinical Trials (www.irct. ir): IRCT201405271556N60 [ABSTRACT FROM AUTHOR]

What is known and objective Cytochrome P450 1A2 ( CYP1A2), CYP2B6 and inducible nitric oxide synthase ( iNOS) are involved in the metabolism and action of many important therapeutic drugs, and genetic variants have been associated with interethnic differences in response to treatment, including chemotherapy. Methods Eight hundred and forty-two unrelated Chinese healthy subjects (323 Tibetan, 134 Mongolian, 162 Uygur and 223 Han) were recruited for genotyping. Frequencies of CYP1A2 -163C>A, CYP2B6 516G>T and iNOS -954G>C were determined by the polymerase chain reaction-restriction fragment length polymorphism ( PCR- RFLP) methods. Results and discussion The frequency of CYP1A2-163A was higher in Chinese Mongolian (0·698) than in Chinese Tibetan (0·633), Uygur (0·633) and Han populations (0·608, P < 0·05), respectively. The frequency of CYP1A2-163A in the Chinese population (total, 0·636) was intermediate between those reported in Caucasians (0·682, P < 0·05) and Africans (0·549, P < 0·01). The frequency of CYP2B6 516T in Chinese Uygur (0·287) was significantly higher than those in Chinese Tibetan (0·147, P < 0·01) and Mongolian (0·179, P < 0·01), respectively, but was similar to the frequency in Chinese Han (0·226). The frequencies of CYP2B6 516T were in the order of Africans (0·500) > Caucasians (0·286) > Chinese (0·200). The variant iNOS-954C was rare in Chinese Tibetan (0·005), Mongolian (0·004), Uygur (0·000) and Han (0·007), respectively, but showed higher frequencies in African ethnic groups. The frequencies of iNOS-954C were in the order of Africans (0·098) > Chinese (0·004) > Caucasians (0·000). What is new and conclusion This is the first report of the distribution frequencies of functional CYP1A2, CYP2B6 and iNOS genes among mainland Chinese Tibetan, Mongolian, Uygur and Han populations. These results should help inform studies of interethnic differences in disease susceptibility or drug responses. [ABSTRACT FROM AUTHOR]

What is known and objective Adjustment of drug dosage in patients with end-stage renal disease prevents serious adverse effects, which occur due to the accumulation of drugs or other toxic metabolites. Nevertheless, dosing errors occur most commonly among patients with end-stage renal disease. The aim of this study was to assess the quality of care for end-stage renal disease outpatients using their renal dosing adjustment status. Methods A cross-sectional study was performed using the data collected from 43 South Korean medical institutions via questionnaires. A total of 2428 patients on haemodialysis, who were at least 18 years of age, were included. Among these patients, the study population was confined to patients who were taking medications and required renal dosing adjustments from three therapeutic classes: antihypertensives, antihyperglycaemics and lipid-modifying agents. The study population ( n = 828) was prescribed a total of 1097 drug orders for the target drugs. Determination of appropriate dosage adjustment was based on GFR (glomerular filtration rate) using the Modification of Diet in Renal Disease revised 4-variable equation. The primary outcome was non-adherence to drug dosing requirements for end-stage renal disease patients with consideration to their renal function. Results and discussion Among the study population ( n = 828), 469 haemodialysis patients were identified as having drug orders that were adherent to renal dosing recommendations. There were significant differences between the patient groups who received recommendation-adherent and non-adherent drug orders in the characteristics of the medical institutions they visited, causes of chronic renal failure and prevalence of concurrent diabetes mellitus. The primary factor of non-adherence to renal dosing adjustment recommendations was characteristics of medical institutions. Compared to tertiary hospitals, secondary hospitals and primary care clinics were 1·16 and 1·22 times, respectively, more non-adherent in accordance with the multivariate analysis ( OR: 1·16, 95% CI: 1·02-1·20, OR: 1·22, 95% CI: 1·00-1·36, respectively). What is new and conclusions Dosing error is one of the most common problems among patients with renal failure. To decrease the dosing errors, an improvement needs to be made in medical institutions. This can be accomplished by implementing the clinical decision support systems that educate physicians on appropriate renal dosing and help them prescribe appropriate drug dosages. [ABSTRACT FROM AUTHOR]

What is new and objectives Trends in the care of glioblastoma in actual practice settings are poorly described. In a previous pharmacoepidemiologic study, we highlighted changes in the management of patients with glioblastoma ( GBM) newly diagnosed between 2004 and 2008. Our aim was to complete and to extend the previous report with a study of a cohort of patients diagnosed in 2011 to emphasize the trends in the pharmacotherapy of GBM over the last decade. Methods A single-centre study was undertaken of three historic cohorts of GBM patients newly diagnosed during years 2004, 2008 and 2011 (corresponding to groups 1, 2 and 3, respectively) but limited to patients eligible for radiotherapy after initial diagnosis. The type of medical management was described and compared, as well as overall survival and total cost from diagnosis to death or the last follow-up date. Cost analysis was performed from the French sickness fund perspective using tariffs from 2014. Results Two hundred and seventeen patients (49 in Group 1, 73 in Group 2, 95 in Group 3) were selected with similar baseline characteristics. Fluorescence-guided surgery using 5- ALA was increasingly used over the three periods. There was a strong trend towards broader use of temozolomide radiochemotherapy (39%, 73% and 83% of patients, respectively) as first-line treatment as well as bevacizumab regimen at recurrence (6%, 48% and 58% of patients, respectively). The increase in overall survival between Group 2 and Group 1 was confirmed for patients in Group 3 (17·5 months vs. 10 months in Group 1). The mean total cost per patient was 53368 € in Group 1, 70 201 € in Group 2 and 78355 € in Group 3. Hospital care represented the largest expenditure (75%, 59% and 60% in groups 1, 2 and 3, respectively) followed by chemotherapy drug costs (11%, 30% and 29%, respectively). What is new and conclusion This is the first study to report on changes in the management of GBM in real-life practice. The ten-year study indicates an improvement in overall survival but also an increase in total cost of care. The data should be useful for informing the care of GBM patients in settings similar to ours. [ABSTRACT FROM AUTHOR]

What is known and objective Regular blood transfusions in the management of myelodysplastic syndrome (MDS) often lead to iron overload. The main objective of this study was to evaluate the impact of medication adherence on the effectiveness of deferasirox for the treatment of transfusional iron overload in patients with MDS. Secondary objectives were to describe treatment effectiveness and safety in daily clinical practice. Methods A longitudinal, retrospective, observational study was carried out in a university hospital. The inclusion criteria were age over 18 years, MDS diagnosis and treatment with deferasirox for transfusion-dependent iron overload during the period of study (from January 2011 to April 2015). Treatment effectiveness was estimated by serum ferritin (SF), and adherence was measured by medication possession ratio (MPR). Clinically relevant analytical alterations during the treatment and reasons for treatment discontinuation were also assessed. Results Thirty-five patients were included in the study. Median SF at baseline was 1636 μg/L, and it decreased to 1399 μg/L during follow-up. The median adherence rate was 92%, although only 54·8% of the patients maintained deferasirox adherence ≥90% during the whole duration of treatment. Adherence rate was inversely correlated to SF ( r = −0·288, P = 0·004). The median (p25, p75) duration of treatment was 11 (3·0, 37·8) months. The most common reasons for treatment discontinuation were renal toxicity (35%) and patient′s death (25%). What is new and conclusion Deferasirox's effectiveness, measured by the decrease in SF, was significantly better in adherent patients. The most frequent reason for treatment discontinuation was renal toxicity. Developing strategies to improve deferasirox treatment adherence and monitoring renal function in those patients should be key points in pharmaceutical care. [ABSTRACT FROM AUTHOR]

What is known and objective The dofetilide label recommends using actual body weight ( ABW) to calculate the Cockcroft-Gault creatinine clearance (CrCl) for the determination of the initial dose; however, few studies have attempted to evaluate this dosing recommendation in overweight and obese patients. We evaluated whether the current dofetilide dosing recommendation based on ABW is appropriate in overweight and obese patients. Methods This is a retrospective cohort study conducted at two large academic medical centres in the United States on overweight and obese patients (body mass index ≥ 25 kg/m2) who were newly started on dofetilide based on ABW. Patients were categorized into (i) the different-dose group if their CrCl calculated based on the ideal body weight ( IBW) resulted in a lower initial dofetilide dose compared with ABW-based CrCl and (ii) the same-dose group if they would have the same initial dose based on IBW and ABW. The primary outcome was dofetilide dose reduction or discontinuation due to prolongation of the corrected QT interval during the first 3 days of dofetilide therapy. Multivariable logistic regression analysis was performed to identify factors predicting the risk of primary outcome. Results and discussion Of the 132 patients included in the study, 29 (22·0%) were in the different-dose group and 40 (30·3%) had the primary outcome. The per cent of patients with the primary outcome was not statistically significantly different between the different-dose and same-dose groups (37·9% vs. 28·2%; P = 0·31). Diabetes mellitus was a significant predictor for the primary outcome (odds ratio 2·54; 95% confidence interval 1·05-6·15). What is new and conclusion Our study provides the evidence on the safety of the current dofetilide dosing recommendation in overweight and obese populations in clinical practice. Current ABW-based dofetilide dosing is reasonable in overweight and obese patients. [ABSTRACT FROM AUTHOR]

What is known and objective Vancomycin is still the first-line treatment for resistant gram-positive infections, particularly for methicillin-resistant Staphylococcus aureus (MRSA) infections. The vancomycin treatment guideline is based on the association between vancomycin trough concentration and clinical outcome. We here present a retrospective analysis of whether the trough level of vancomycin is associated with clinical outcome in Chinese patients with gram-positive infections. Methods Clinical data were collected retrospectively from patients under vancomycin therapeutic drug monitoring in Huashan Hospital from March 2004 to September 2014. Results and discussion A total of 148 inpatients with gram-positive infection were identified and data on their corresponding vancomycin serum trough concentration retrieved. A total of 113 strains of gram-positive bacteria were isolated from 111 patients, including 90 strains of MRSA. Vancomycin was used for 11 to 13 days on average. The overall bacterial eradication rate was 67·3% (76/113), including 61·1% (55/90) for MRSA and 91·3% (21/23) for Enterococcus. Multivariate logistic model analysis showed that vancomycin trough concentration was not associated with clinical outcome (OR: 1·0; 95% CI: 0·92, 1·08, P = 0·9613). The incidence of adverse drug reactions was low and not related to vancomycin trough concentration. What is new and conclusion This retrospective analysis failed to demonstrate an association between vancomycin trough concentration and the clinical and microbiological response. Prospective controlled studies are necessary to further establish the need for the higher trough concentrations normally cited for clinical efficacy. [ABSTRACT FROM AUTHOR]

What is known and objective Clostridium difficile infection ( CDI) represents a spectrum of disease and is a significant concern for healthcare institutions. Our study objective was to assess whether implementation of a regional CDI management policy with Clinical Pharmacy and Medical Microbiology and Infection Control involvement would lead to an improvement in concordance in prescribing practices to an evidence-based CDI disease severity assessment and pharmacological treatment algorithm. Methods Conducted at a tertiary care teaching hospital, this two-phase quality assurance study consisted of a baseline retrospective healthcare record review of patients with CDI prior to the implementation of a regional CDI management policy followed by a prospective evaluation post-implementation. Results and discussion One hundred and forty-one CDI episodes in the pre-implementation group were compared to 283 episodes post-implementation. Overall treatment concordance to the CDI treatment algorithm was achieved in 48 of 141 cases (34%) pre-implementation compared with 136 of 283 cases (48·1%) post-implementation ( P = 0·01). The median time to treatment with vancomycin was reduced from five days to one day ( P < 0·01), with median length of hospital stay decreasing from 30 days to 21 days ( P = 0·01) post-implementation. There was no difference in 30-day all-cause mortality. What is new and conclusion A comprehensive approach with appropriate stakeholder involvement in the development of clinical pathways, education to healthcare workers and prospective audit with intervention and feedback can ensure patients diagnosed with CDI are optimally managed and prescribed the most appropriate therapy based on CDI disease severity. [ABSTRACT FROM AUTHOR]

What is known and objective Anecdotally, topical kunzea oil has been used to treat various skin conditions, including psoriasis and eczema, with good results. This study compared the clinical efficacy of kunzea oil (20%)-containing formulations in mild to moderate psoriasis. Methods A randomized, comparative, double-blind, 8-week study was undertaken. Thirty patients (age range: 25-74 years and mean ± SD: 52·8 ± 13·6 years) with mild to moderate psoriasis (affecting at least 10% of one or more body regions: arms, head, legs and trunk) randomly received ointment and/or scalp lotion containing 20% kunzea oil (test group) or control medications not containing kunzea oil (control group). Formulations in both treatment arms also contained 5% liquor carbonis detergens ( LCD) and 3% salicylic acid. The clinical responses to the test and control formulations were evaluated using the Psoriasis Area and Severity Index ( PASI). Results and discussion After 8 weeks of treatment, both test and control groups demonstrated a significant ( P < 0·05) improvement in PASI scores. Subjects in the test group had a decrease in mean± SD PASI score from 12·7 ± 7·9 to 6·7 ± 7·2, whereas the control group showed a decrease in PASI score from 8·1 ± 4·6 to 3·5 ± 4·7. Comparative efficacy analysis between the test and control groups did not reveal any significant difference ( P > 0·05). What is new and conclusions The inclusion of kunzea oil made no difference to the efficacy of topical formulations containing LCD and salicylic acid for the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

What is known and objective Esophagogastroduodenoscopy ( EGD) is a common diagnostic procedure which requires sedation for most patients. We undertook a prospective, randomized, double-blinded study to compare the effect of propofol vs. dexmedetomidine on the sedation of outpatients during EGD. Methods Prior to the procedure, outpatients received either propofol at 0·6 mg/kg, with additional doses of 10-20 mg until the Observer's Assessment of Alertness/Sedation Scale ( OAA/S) score reached 2-4, or dexmedetomidine at a loading dose of 1 μg/kg over a 10-min period followed by a 0·5 μg/kg/h infusion until the OAA/S score reached 2-4. Vital signs, sedation level, adverse events, patients' and endoscopist's satisfaction score, and an evaluation of the recovery time were assessed. Results and discussion Negligible haemoglobin oxygen saturation (SpO2) and respiratory rate variations were observed in both groups, although respiratory depression occurred in two cases (5·9%) in the propofol group. Mean arterial pressure ( MAP) in the propofol group decreased during the procedure compared with baseline ( P < 0·05) and was also lower in comparison with the dexmedetomidine group ( P < 0·05). Heart rate ( HR) decreased after the loading dose in the dexmedetomidine group ( P < 0·05). More patients in the propofol group underwent deeper sedation at the beginning of the procedure ( P < 0·05), although the recovery time was comparable between the two groups ( P > 0·05). Three cases (9·1%) in the dexmedetomidine group were delayed because of dizziness, bradycardia and nausea. There was a higher satisfaction score among patients in the propofol group ( P < 0·05), although the endoscopist's satisfaction score was comparable between the two groups ( P > 0·05). What is new and conclusion Propofol and dexmedetomidine provide a relatively satisfactory level of sedation without clinically notable adverse effects during EGD. In addition, patients preferred propofol administration for the deeper sedation and rapid recovery, and dexmedetomidine exhibited minimal adverse effects on respiratory function. [ABSTRACT FROM AUTHOR]

What is known and objective Depression is a debilitating complication of brucellosis and how best to treat this is a matter of debate. Inflammatory processes are involved in the pathogenesis of both brucellosis and depression. Therefore, we hypothesized that celecoxib could be beneficial for the treatment of depression due to brucellosis. Methods Forty outpatients with depression due to brucellosis with a Hamilton Depression Rating Scale score ( HDRS) <19 participated in a randomized, double-blind, placebo-controlled trial and underwent 8 weeks of treatment with either celecoxib (200 mg bid) or placebo as an adjunctive to antibiotic therapy. Patients were evaluated using HDRS at baseline and weeks 4 and 8. Result and discussion Repeated-measures analysis demonstrated significant effect for time × treatment interaction on the HDRS score [ F (1·43, 57·41) = 37·22, P < 0·001]. Significantly greater response to treatment occurred in the celecoxib group than in the placebo group at the study end [10 patients (50%) vs. no patient (0%), respectively, P < 0·001]. No serious adverse event was observed. What is new and conclusion Celecoxib is a safe and effective treatment for depression due to brucellosis when compared with placebo. [ABSTRACT FROM AUTHOR]

What is known and objective Since their introduction, tyrosine kinase inhibitors ( TKIs) have been increasingly used in clinical practice. We describe the prescribing and the clinical and biological consequences of two such inhibitors, imatinib and erlotinib, in patients with chronic myeloid leukaemia ( CML) in a practice setting over a period of more than 10 years. Methods All patients who received at least one TKI for chronic phase CML between 2001 and 2012 in our university hospital were included in the study. Results and discussion Of the 139 patients, with a median age of 57 years, who were surveyed, imatinib and nilotinib were prescribed as the first TKI in 131 (94%) and 8 (6%) patients, respectively. With a median follow-up of 6 years, 342 treatment modifications were observed: 113 (33%) increased doses, 109 (32%) decreased doses, 89 (26%) TKI changes, 14 (4%) definitive discontinuations, 13 (4%) temporary discontinuations and 4 (1%) additions of IFN-α. The main reasons for the 342 treatment modifications were adverse events ( n = 112, 33%), long-term optimal response ( n = 58, 17%) and failure ( n = 57, 17%). Eighty-five (61%), 31 (22%), 18 (13%) and 5 (4%) patients had no, 1, 2 and 3 TKI changes, respectively. Imatinib was the most prescribed TKI (75%). Adverse events resulting in treatment modifications occurred in 18% of patients for imatinib, 49% for nilotinib and 41% for dasatinib ( P < 0·001). Median time to TKI change whatever the reason was >50 months (not achieved) for imatinib, 22 months for nilotinib and 27 months for dasatinib (log-rank test, P < 0·001). What is new and conclusion Imatinib was the most prescribed TKI both in the first and in subsequent therapeutic lines for chronic phase CML. Our study showed a very good efficacy-safety profile for imatinib at a median follow-up of 6 years in an unselected French population. [ABSTRACT FROM AUTHOR]

What is known and objective: The Food and Drug Administration (FDA) instituted a risk evaluation mitigation strategy (REMS) for erythropoiesis-stimulating agent (ESA) use in patients with cancer in February 2010. Implementation of REMS was considered likely to reduce ESA use and increase red blood cell transfusions. We aimed to quantify ESA and transfusion use pre- and post-REMS. Methods: A retrospective data analysis was conducted using the Medicare 5% Sample Database from 2008 through 2011. Patients were 66 years of age or older and had lung and/or breast cancers along with chemotherapy-induced anaemia. Patients initiated chemotherapy in pre-REMS and post-REMS periods (1Q2008 through 4Q2009 and 1Q2010 through 4Q2011, respectively). Logistic regression was used to evaluate differences in proportions of patients receiving ESAs and transfusions pre-REMS and post-REMS. Results and discussion: The pre-REMS group included 1526 patients and the post-REMS group included 1689 patients. ESA use in patients with lung cancer decreased 302%from pre- to post- REMS and 331% in patients with breast cancer. Both decreases were statistically significant. Transfusion rates increased 221% from the pre-REMS period to the pre-REMS period in patients with breast cancer (P < 00001), but there was no statistically significant change over time in patients with lung cancer. What is new and conclusion: Erythropoiesis-stimulating agent use decreased in patients with both lung and breast cancer (P < 00001), and transfusion rates increased significantly post- REMS in patients with breast cancer (P < 00001) but not in those with lung cancer. [ABSTRACT FROM AUTHOR]

What is known and objective: Linezolid (LZD) is an oxazolidinone antibiotic that is active against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus and vancomycin- resistant enterococci. The major adverse effect related to its use in humans is reversible myelosuppression, which mostly manifests as thrombocytopenia. This retrospective study was conducted to identify risk factors that might contribute towards the development of thrombocytopenia due to intravenous administration of LZD. Method: Patients who were administered LZD between January 2008 and March 2013 were included. Thrombocytopenia was defined as a decrease in platelet count of =10 3 104 cell/lL from baseline or of =30%. Results: A total of 47 patients were included in this study. These patients were divided into two groups: 22 patients (468%) were assigned to a non-thrombocytopenia group and 25 patients (532%) to a thrombocytopenia group. Multivariate logistic regression analysis revealed significant intergroup differences in duration of LZD treatment [odds ratio (OR) = 1278; 95% confidence interval (CI) = 1068-1529; P = 0007] and white blood cell (WBC) count (>12000 cells/lL; OR = 10399; 95% CI = 1667-64882; P = 0012). What is new and conclusions: This finding suggests that duration of LZD treatment and WBC count (>12000 cells/lL) are risk factors associated with thrombocytopenia resulting from LZD administration. [ABSTRACT FROM AUTHOR]

What is known and objectives The French Society of Clinical Pharmacy has developed a website, named Act-IP©, enabling hospital pharmacists to document and analyse pharmacists' interventions (PIs) proposed during medication order review when a drug-related problem is detected. This study analyses PIs documented in Act-IP© and assesses factors associated with physicians' acceptance of PIs. Methods PIs documented into Act-IP© over a 30-month period were analysed. Independent predictors of physicians' acceptance were assessed using multiple logistic regression. Results and discussion A total of 34 522 PIs were registered by 201 pharmacists working in 59 hospitals. PIs were mostly related to 'dose adjustment' (25%), 'drug discontinuation' (20%) and 'drug switch' (19%). Of the 43 343 medications involved, 28% targeted drugs acting on the central nervous system, 17% anti-infective drugs and 16% cardiovascular drugs. Sixty-eight per cent of PIs were accepted by physicians (15% refusals and 17% non-assessable). Physicians' acceptance was significantly associated with 1/ drug group: antineoplastics and immunomodulators (OR = 2·29, CI 95[1·94-2·69]), anti-infectives (OR = 1·19, CI 95 [1·11-1·28]); 2/ type of intervention: drug switch (OR = 1·54, CI 95 [1·43-1·65]), drug discontinuation (OR = 1·38, CI 95 [1·29-1·48]), administration modality optimization (OR = 1·19, CI 95 [1·11-1·29]), addition of a new drug (OR = 1·12, CI 95 [1·00-1·24]); 3/ ward specialty: paediatrics (OR = 1·83, CI 95 [1·24-2·70]) and intensive care (OR = 1·34, CI 95 [1·10-1·64]); 4/ level of pharmacist integration in the ward: higher when the pharmacist is regularly in the ward compared with occasionally (OR = 0·74, CI 95 [0·70-0·79]) or never (OR = 0·68, CI 95 [0·60-0·75]) present. What is new and conclusion This study highlights the role of routine pharmacist review of medication orders to prevent drug-related problems and gives new insights for a successful collaboration between physicians and pharmacists. [ABSTRACT FROM AUTHOR]

What is known and objectives Patients undergoing Roux-en-Y gastric bariatric ( RYGB) surgery present a reduced absorption site, and special attention should therefore be taken when prescribing oral-dosage forms. This study was carried out to investigate the extent to which non-bariatric clinicians are aware of this issue when prescribing medicines for this population, and what type of information is available to aid them in their decision-making. Methods Two questionnaires were created, one for non-bariatric clinicians and another for their patients who had undergone RYGB surgery, to gather information about the prescription practices for this population. Additionally, a literature search of pharmacokinetic studies on bariatric patients and recommended prescription practices was carried out. Results and discussion Of the 62 non-bariatric clinicians surveyed, 50% believed RYGB surgery interferes with drug absorption; however, 68% still prescribed tablets as the first choice form of dosage. Young clinicians (35%) were less likely to believe that RYGB surgery could affect drug absorption than experienced clinicians (43%). The main reasons for changing dosage forms were patient complaints about efficacy or difficulty in swallowing tablets. Of the 73 patients, 43 were taking drugs in tablet form after the surgery, 24 of whom had health issues unrelated to the surgery. None of the journals read by the clinicians contained pharmacokinetics ( PK) studies involving bariatric surgery patients or presented recommendations for the prescription of oral-dosage forms for this population. The literature search revealed a total of 22 drugs that had undergone PK studies in RYGB patients. Fifteen of them were reported to have decreased effects, 12 of which were administered as tablets. What is new and conclusion There is still a relative lack of clinical evidence to guide clinicians when prescribing medicines for bariatric patients. It is therefore recommended that pharmacists should have greater participation in the prescription process to advise non-bariatric clinicians and educate RYGB surgery patients to help avoid therapeutic failure. [ABSTRACT FROM AUTHOR]

What is known and objective Drug eluting beads ( DEBs) theoretically improve the efficacy and safety of transarterial chemoembolization ( TACE) in hepatocellular carcinoma ( HCC). Nonetheless, their economic profile has not been assessed. Our retrospective before/after study aimed to compare efficacy, safety and economic profile of two strategies of TACE without (Period 1) or with the possibility of using DEBs (Period 2). Methods All HCC patients treated by TACE in our hospital between March 2006 and May 2013 were included. Economic analyses were performed from the French Public Health Insurance point of view according to the French Diagnosis-Related Group prospective payment system and from the analytic accountability. Results and discussion One hundred and sixty-one patients were included. Median time to treatment failure and overall survival were 13·1 and 23·8 months in Period 1 vs. 14·1 and 30·2 months in Period 2 ( P = 0·45 and P = 0·40). Mean hospital durations and tariffs were 14·9 ± 7·7 days and € 11 472 ± 5901 in Period 1 vs. 12·4 ± 8·4 days and € 7654 ± 4625 in Period 2 ( P = 0·03 and P < 10−4). What is new and conclusion The possibility of using DEBs did not improve the prognosis in HCC patients treated by TACE. Nonetheless, it had a better medico-economic profile. [ABSTRACT FROM AUTHOR]

What is known and objective The risk of dosage Prescription Medication Error ( PME) among manually written prescriptions within 'mixed' prescribing system (computerized physician order entry ( CPOE) + manual prescriptions) has not been previously assessed in neonatology. This study aimed to evaluate the rate of dosage PME related to manual prescriptions in the high-risk population of very preterm infants ( GA < 33 weeks) in a mixed prescription system. Methods The study was based on a retrospective review of a random sample of manual daily prescriptions in two neonatal intensive care units ( NICU) A and B, located in different French University hospitals ( Dijon and La Reunion island). Daily prescription was defined as the set of all drugs manually prescribed on a single day for one patient. Dosage error was defined as a deviation of at least ±10% from the weight-appropriate recommended dose. Results and discussion The analyses were based on the assessment of 676 manually prescribed drugs from NICU A (58 different drugs from 93 newborns and 240 daily prescriptions) and 354 manually prescribed drugs from NICU B (73 different drugs from 131 newborns and 241 daily prescriptions). The dosage error rate per 100 manually prescribed drugs was similar in both NICU: 3·8% (95% CI: 2·5-5·6%) in NICU A and 3·1% (95% CI: 1·6-5·5%) in NICU B ( P = 0·54). Among all the 37 identified dosage errors, the over-dosing was almost as frequent as the under-dosing (17 and 20 errors, respectively). Potentially severe dosage errors occurred in a total of seven drug prescriptions. None of the dosage PME was recorded in the corresponding medical files and information on clinical outcome was not sufficient to identify clinical conditions related to dosage PME. Overall, 46·8% of manually prescribed drugs were off label or unlicensed, with no significant differences between prescriptions with or without dosage error. The risk of a dosage PME increased significantly if the drug was included in the CPOE system but was manually prescribed ( OR = 3·3; 95% CI: 1·6-7·0, P < 0·001). What is new and conclusion The presence of dosage PME in the manual prescriptions written within mixed prescription systems suggests that manual prescriptions should be totally avoided in neonatal units. [ABSTRACT FROM AUTHOR]

What is known and objective Therapeutic options for the management of glioblastoma ( GBM) have greatly evolved over the last decade with the emergence of new regimens combining radiotherapy plus temozolomide and the use of bevacizumab at recurrence. Our aim was to assess the clinical and economic impacts of those novel strategies in our center. Methods A single-center retrospective chart review was conducted on patients newly diagnosed with a GBM over two periods (year 2004, group 1 or year 2008, group 2) with limitations to those eligible to radiotherapy after initial diagnosis. The type of medical management was described and compared, as well as overall survival and total costs from diagnosis to death or the last follow-up date. Cost analysis was performed under the French Sickness Fund perspective using tariffs from 2012. Results One hundred twenty-two patients were selected (49 in group 1 and 73 in group 2) with similar baseline characteristics within the two groups. Patients from group 2 received more frequently temozolomide radiochemotherapy (71% vs. 39%, P < 0·05) as first-line treatment as well as bevacizumab regimen at recurrence (48% vs. 6%, P < 0·05); the median overall survival was increased between the two periods (respectively 17 vs. 10 months, P < 0·05). The mean total cost per patient was 54 388 € in group 1 and 71 148 € in group 2 ( P < 0·05). Hospital care represented the largest expenditure (76% and 58% in groups 1 and 2 respectively) followed by chemotherapy drugs costs (11% and 30% respectively). The total cost difference between the two groups was explained by the increasing use of temozolomide and bevacizumab. The incremental cost-effectiveness ratio was estimated at 54 355 € per life-year gained. What is new and conclusion As far as we know, this is the first study reporting the total cost of GBM management based on the French perspective, as well as the cost-effectiveness of clinical practices in term of cost per life-year gained. Those novel strategies have contributed to improve overall survival while inducing a substantial, but acceptable, increase of total costs. [ABSTRACT FROM AUTHOR]

What is known and objective Drug lag is a major public concern in Japan. During the development of new drugs, some factors related to clinical trials in the marketing application package, such as trial design and the number of trials, can affect drug approval. The aim of this study was to determine whether those clinical trial factors were associated with drug lag in Japan. Methods We investigated new drug applications for new molecular entities that were approved in Japan between April 2009 and March 2012. We collected information on clinical trials in the marketing application package from review reports. Results and discussion We constructed a multiple regression model to predict drug lag using the review period, use of foreign clinical trial data, the number of confirmatory trials, the design of the pivotal trial, failures of confirmatory trials and the death rate ( n = 59). No use of foreign trial data was significantly associated with a longer drug lag (84% increase; 95% confidence interval [ CI], 1·03-3·29). Compared to the open-label, one-armed design, drugs that underwent pivotal trials of placebo-controlled superiority, active-controlled superiority and active-controlled non-inferiority designs had a significantly shorter drug lag (74% decrease, 95% CI: 0·08-0·83; 74% decrease, 95% CI: 0·07-0·99; and 85% decrease, 95% CI: 0·04-0·58, respectively). What is new and conclusion Our findings suggest that new drug application packages that do not use data from foreign clinical trials and that involve pivotal trials of open-label, one-armed design contribute to drug lag in Japan. To reduce this lag, improved strategies for the development of new drugs should be identified. [ABSTRACT FROM AUTHOR]

What is known and objective The CHOP regimen with rituximab (R- CHOP) remains the standard for chemotherapy in patients with aggressive non-Hodgkin's lymphoma ( NHL). The cardiotoxicity of doxorubicin appears to be a key problem in clinical practice. We studied the cardiotoxicity of CHOP/R- CHOP regimen in a retrospective series. The prognostic factors of congestive heart failure ( CHF) were investigated, including the impact of empirical cardioprotection by dexrazoxane. Methods Patients with an aggressive NHL between 1994 and 2005 were included. Cardiac events were defined as either a decline in resting left ventricular ejection fraction ( LVEF) <50%, a decline in LVEF of ≥20% from baseline or as clinical evidence of CHF. The risk of cardiotoxicity was explored by the Kaplan-Meier method. Results The study included 180 consecutive patients. During the second period of the survey, cardioprotective therapy by dexrazoxane was administered to 45% of patients. The 5-year cumulative risks of cardiac events (29% vs. 8%) and clinical CHF (17% vs. 1·5%) varied significantly between the two periods of study (1994-2000 vs. 2001-2005). In multivariate analysis, use of dexrazoxane ( HR = 0·1 [0·01-0·75], P = 0·02) and age < 60 years ( HR = 0·4 [0·17-0·9], P = 0·03) appeared as protective factors of cardiac events. What is new and conclusion Our study confirmed the weight of cardiac toxic effect of CHOP ± R regimen. Even if the use of dexrazoxane is highly debatable in curative situations, it may be an effective prevention of cardiotoxicity in aggressive NHL patients. [ABSTRACT FROM AUTHOR]

What is known and objective Probiotic therapy has been shown to reduce morbidity and mortality of necrotizing enterocolitis ( NEC) in premature infants in several international studies using various probiotic agents. The purpose of this study* is to describe our experience of using probiotic therapy in preventing NEC in infants with very low birth weight ( VLBW) in a neonatal intensive care unit ( NICU) and to evaluate whether our records provide evidence of effectiveness for probiotic therapy. Methods In a retrospective cohort study, the efficacy of probiotic therapy in preventing NEC in VLBW infants was investigated via chart review. A probiotic administration protocol using a three-strain ( Streptococcus thermophilus, Bifidobacterium infantis and Bifidobacterium bifidum) supplement was implemented in August 2007. Patients admitted to the NICU from August 2003 through July 2011 were screened. Primary outcomes are the morbidity and mortality of NEC. The secondary outcomes were severity of NEC and incidence of where infant feeds were stopped but NEC was not diagnosed ( NEC scare). Results and Discussion There was a significant increased baseline risk of NEC development in the probiotics group, including younger gestational age, higher incidence of patent ductus arteriosus ( PDA) and use of indomethacin. The incidence of NEC is similar between the control group (2·8%) and probiotics group (2·4%) (hazard ratio, 1·15; 95% confidence interval [ CI], 0·42, 3·12). Mortality of NEC is also not statistically different. Incidence of NEC scare was decreased from 2·8% in control group to 1·4% in probiotics group, although the difference was not statistically significant ( P = 0·38). What is known and conclusion Our findings suggest that probiotics are safe in NEC prevention in VLBW infants. We had no cases of infection related to the strains of bacteria used in our product. With the low incidence of NEC (2·8%) and NEC scare (2·8%) in our cohort, we do not have enough power to detect any change in outcome, particularly as our study was observational. However, it is hoped that our data give useful information for others on probiotic prophylactic therapy in the routine clinical management of VLBW infants. [ABSTRACT FROM AUTHOR]

What is known and objective Although the long-term infusion of ANP has proved effective to treat heart failure, no published randomized controlled study has been reported to confirm the efficacy of the short-term ANP infusion in congestive heart failure ( CHF) patients. This study was designed to assess the efficacy and safety of short-term infusion of recombinant human atrial natriuretic peptide (rh ANP) in CHF patients. Methods A total of 48 patients with CHF were enrolled and randomized into four groups, treated with standard therapy or rh ANP (0·05, 0·1 or 0·2 μg/kg/min) for 1-hour infusion in addition to standard therapy. The hemodynamics were assessed for 12 h by Swan-Ganz catheter. Results and discussion The effect of the 0·05 μg/kg/min rh ANP dose group on CO was modest and transient. The 0·2 μg/kg/min rh ANP dose group tended to be associated with better effect on SV, CO and dyspnoea improvement, but modest effect on PCWP and more adverse events probably attributed to the study drug. However, the 0·1 μg/kg/min rh ANP infusion was well tolerated and effective both on PCWP decrease (maximum:−9·46 ± 5·81 mmHg compared with baseline ( P = 0·0002) and −6·75 mmHg compared with standard therapy, the 95% confidential interval [−13·43, −0·06 mmHg] at 1 h) and CO increase (maximum: 1·02 ± 1·43 L/min [ P = 0·0308] at 1 h). What is new and conclusion In this small-sample study, 1-hour infusion of rh ANP produced beneficial hemodynamic effects in CHF patients compared with standard therapy, and it was well tolerated. 0·1 μg/kg/min may be the optimum dose for short-term rh ANP infusion to treat CHF for the further large sample trial before clinical application. [ABSTRACT FROM AUTHOR]

SUMMARY What is known and Objective: Somatostatin (SST) is used for the treatment of acute variceal bleeding based on its ability to decrease portal pressure and collateral blood flow. To date, no studies have focused on the immediate-early effects (between 1 and 30 min) of SST. The aim of this study was to compare the efficacy of different schedules of SST therapy with placebo on portal pressure in patients with portal hypertension treated with portal-azygous disconnection and to test whether an increase in bolus or infusion dose can improve the clinical efficacy of SST therapy. Methods: Patients were treated with four different schedules: (a) standard dose ( n = 11): one 250 μg bolus + a continuous infusion of 250 μg/h; (b) medium dose ( n = 10): 500 μg bolus + a continuous infusion of 250 μg/h; (c) high dose ( n = 10): 250 μg bolus + a continuous infusion of 500 μg/h; (d) control ( n = 10): an injection of placebo (saline) followed by a placebo infusion. Following SST or placebo administration, portal pressure, central venous pressure (CVP), systemic blood pressure and heart rate (HR) were measured at 1, 3, 5, 7, 10 and 30 min. Results and Discussion: The three schedules of SST induced a marked, rapid and highly significant decrease in portal pressure. The decline in portal pressure was moderate at 1 min ( P < 0·040), achieved a peak effect at 5 min ( P < 0·009) and remained decreased at 30 min. The effect of SST on portal pressure was significantly greater than placebo from 1 min after administration. There were no significant differences in portal pressure decrease between the three schedules of SST. The three schedules of SST and the placebo schedule did not induce significant changes in HR, systemic blood pressure and CVP. What is new and Conclusion: This study shows that SST is effective in decreasing portal pressure within 30 min of administration in patients with liver cirrhosis. The clinical schedule used in this study was reasonable and safe. [ABSTRACT FROM AUTHOR]

What is known and objective: High costs of novel agents increasingly put pressure on limited healthcare budgets. Demonstration of their real-world costs and cost-effectiveness is often required for reimbursement. However, few published economic evaluations of novel agents for multiple myeloma exist. Moreover, existing cost analyses were heavily based on conventionally treated patients. We investigated real-world health care costs of relapsed/refractory multiple myeloma in Dutch daily practice. Methods: A retrospective medical chart review was conducted for 139 patients treated between January 2001 and May 2009. Total monthly costs attributable to each cost component were described across all regimens and for bortezomib-, thalidomide- and lenalidomide-based treatment regimens. Results: Mean monthly total costs (€3,981) varied depending on the sequence of therapy (range: €442-€31,318). Significant cost drivers across all regimens included costs of therapy and hospital admissions. The acquisition costs for novel agents in particular accounted for 32% of mean total monthly costs. Prognostic factors associated with increased mean total monthly costs in multivariate regression analysis included low platelet counts ( P = 0·01) and worsening performance status ( P < 0·001). Mean total monthly costs of bortezomib- and lenalidomide-based regimens were significantly higher than those for thalidomide-based regimens in second, third and fourth treatment line. What is new and conclusions: Real-world costs during treatment of relapsed/refractory multiple myeloma vary greatly. Cost drivers include hospital admissions and acquisition costs of novel agents. Costs also vary by prognostic factors and treatment-related resource use. Future studies assessing the costs of combination therapy consisting of two or more novel agents are encouraged. [ABSTRACT FROM AUTHOR]

What is known and Objective: Hyperglycaemia in trauma patients admitted to the intensive care unit (ICU) is associated with increased morbidity and mortality. Our pilot study is a prospective randomized controlled trial comparing the impact of two glucose control regimens on outcomes in non-diabetic trauma patients admitted with hyperglycaemia to the ICU. Methods: Trauma patients with blood glucose levels (BGLs) ≥7·8 m m within the first 48 h of the hospital admission were randomized to receive intermittent SQ or continuous IV insulin to maintain BGLs between 4·4 and 6·1 mm. We excluded diabetics on the basis of history, or a glycosylated haemoglobin ≥6% on admission. We compared the effect of SQ vs. IV insulin therapy on the ICU length of stay (ILOS). Results and Discussion: A total of 58 patients were included in the study. The SQ and IV groups were comparable in terms of age, gender, injury severity, revised trauma, Glasgow coma scores and type of trauma (blunt vs. penetrating). There was no significant difference between the two treatment groups in the ILOS (3 vs. 2 days, P = 0·084), hospital length of stay (8 vs. 6, P = 0·09), ventilator support days (6 vs. 3, P = 0·98), requirement for blood transfusion ( P = 0·66), rates of infections ( P = 0·70), acute kidney injury ( P = 0·99) and mortality ( P = 0·61). What is new and Conclusion: There was no difference between SQ and IV insulin therapy in the ILOS in non-diabetic trauma patients. [ABSTRACT FROM AUTHOR]

What is known and Objective: Anti-tuberculosis drugs (ATD), although highly effective, often cause liver injury. Glutathione S-transferases (GST) play a crucial protective role in the detoxifying mechanisms of drugs. Several studies have investigated the genetic null variants of GSTM1 and GSTT1 as possible risk factors for ATD-induced liver injury; however, those findings are inconsistent. We investigated GSTM1 and GSTT1 null genotypes in Brazilian patients with tuberculosis (TB), adjusting for other possible predictors of ATD-induced liver injury. Methods: This was a prospective cohort study with patients who were treated for TB from 2006 to 2011. GSTM1 and GSTT1 gene deletions were analysed from genomic DNA by polymerase chain reaction (PCR). Demographic, clinical and laboratory data were extracted from medical records and possible predictors of liver injury were evaluated. Results and Discussion: This study enrolled 177 patients. Anti-tuberculosis drugs-induced liver injury incidence was 33·3%. Hepatitis B infection (HBV) and increased alanine aminotransferase (ALT) baseline were significant predictors. Neither GSTM1 nor GSTT1 null genotypes were associated with ATD-induced liver injury; nevertheless, the comparison among four different liver toxicity grades showed that GSTM1 non-null genotype was significant more frequent among the higher grades of liver toxicity. What is new and Conclusion: GSTM1 and GSTT1 null genotypes do not seem to play important roles in ATD-induced liver injury in Brazilians. However, there was evidence that GSTM1 polymorphisms were possibly related to the intensity of toxicity. Active HBV and initial high ALT could predict ATD-induced liver injury. [ABSTRACT FROM AUTHOR]

What is known and objective: Interventions involving medication reconciliation and review by clinical pharmacists can reduce drug-related problems and improve therapeutic outcomes. The objective of this study was to examine the impact of routine admission medication reconciliation and inpatient medication review on emergency department (ED) revisits after discharge. Secondary outcomes included the combined rate of post-discharge hospital revisits or death. Methods: This prospective, controlled study included all patients hospitalized in three internal medicine wards in a university hospital, between 1 January 2006 and 31 May 2008. Medication reconciliation on admission and inpatient medication review, conducted by clinical pharmacists in a multiprofessional team, were implemented in these wards at different times during 2007 and 2008 (intervention periods). A discharge medication reconciliation was undertaken in all the study wards, during both control and intervention periods. Patients were included in the intervention group ( n = 1216) if they attended a ward with medication reconciliation and review, whether they had received the intervention or not. Control patients ( n = 2758) attended the wards before implementation of the intervention. Results and Discussion: No impact of medication reconciliation and reviews on ED revisits [hazard ratio (HR), 0·95; 95% confidence interval (CI), 0·86-1·04]or event-free survival (HR, 0·96; 95% CI, 0·88-1·04) was demonstrated. In the intervention group, 594 patients (48·8%) visited the ED, compared with 1416 (51·3%) control patients. In total, 716 intervention (58·9%) and 1688 (61·2%) control patients experienced any event (ED visit, hospitalization or death). Because the time to a subsequent ED visit was longer for the control as well as the intervention groups in 2007 than in 2006 ( P < 0·05), we re-examined this cohort of patients; the proportion of patients revisiting the ED was similar in both groups in 2007 ( P = 0·608). What is new and conclusion: Routine implementation of medication reconciliation and reviews on admission and during the hospital stay did not appear to have any impact on ED revisits, re-hospitalizations or mortality over 6-month follow-up. [ABSTRACT FROM AUTHOR]

What is known and Objective: Some antimicrobial agents are active in vitro against Leptospiras. The use of penicillins at the late stage of leptospirosis is still controversial. We aimed to evaluate the use of penicillin in patients with leptospirosis-associated acute kidney injury (AKI). Methods: A retrospective study was conducted of patients with leptospirosis admitted to two hospitals in Fortaleza city, Brazil, between 1985 and 2008. AKI was defined according to the RIFLE and AKIN classifications. Patients were divided in two groups according to whether they were treated with a penicillin or not. Results: Two hundred and eighty-seven patients were included, with an average age of 36·8 ± 15·6 years and mostly male (80·8%). One hundred and twelve patients (39%) received a penicillin. Patients treated with a penicillin were younger (32 ± 14 years vs. 39 ± 16 years, P = 0·0002) and had a shorter hospital stay (8·4 ± 5·0 vs. 11 ± 7·7 days, P < 0·0001). There was no difference in the onset of symptoms before hospital admission between the two groups (6·5 ± 3·0 vs. 7·7 ± 4·7, P = 0·33). Systolic blood pressure was lower in the penicillin group (111 ± 21 vs. 119 ± 22 mmHg, P = 0·04). AKI, need of dialysis and renal recovery at the time of hospital discharge were more frequent in patients who did not use a penicillin ( P < 0·05). Mortality was similar in both groups (11·6% vs. 13·7%, P = 0·60). Conclusion: Treatment of leptospirosis with antibiotics, including the penicillin, remains controversial. The main benefit of using penicillin in the present study was a reduction in the length of hospital stay and fewer complications, such as AKI, but its use was not associated with a decrease in mortality. On balance of risks and benefits, we recommend the use of penicillin in late-stage leptospirosis. [ABSTRACT FROM AUTHOR]

What is known and Objective: CYP2C19*17 allele increases the metabolic activity of CYP2C19 resulting in decreased therapeutic levels of CYP2C19 substrates. There exist inter-ethnic differences in the distribution of this allele. The present study was aimed at establishing the allele and genotype frequencies of CYP2C19*17 in a South Indian Tamilian population. Furthermore, we describe the haplotype structure of the three common variant alleles of CYP2C19 in the Tamilian population. Methods: Two hundred and six subjects of South Indian Tamilian origin were genotyped for CYP2C19*17 allele by nested polymerase chain reaction and restriction fragment length polymorphism. A subset of 87 subjects were also genotyped for CYP2C19*2 and CYP2C19*3 alleles. After ascertaining linkage disequilibrium (LD), haplotypes were constructed. Allele and genotype frequencies, LD pattern and haplotype frequency were compared with those of the HapMap populations. Results and Discussion: The CYP2C19*17 allele frequency in the Tamilian population ( n = 206) was found to be 19·2% (95% CI: 15·4 - 20·3). The CYP2C19*2 allele frequency ( n = 87) was found to be 40·2% (95% CI: 32·9 - 47·5), whereas the CYP2C19*3 allele was not detected in the study subjects ( n = 97). The high frequency of the CYP2C19*17 allele in the study population has resulted in a revision of frequencies for CYP2C19*1/*2 (31·0%) and CYP2C19*1/*1 (16·1%) genotypes in the Tamilian population. We also observed significant differences in haplotype structure and frequencies of these variant alleles in the HapMap population compared to Tamilian population. What is new and conclusion: CYP2C19*17 allele is present at high frequency in the Tamilian population. This study also demonstrates the need for reassessment of wild-type allele frequencies in view of CYP2C19*17 allele. The estimated high frequency of CYP2C19*17 allele will aid in genotype-phenotype association studies in the Tamilian population. Further genotype-phenotype association studies are required to evaluate the clinical utility of this allele in South Indians. [ABSTRACT FROM AUTHOR]

What is known and Objective: Cytochrome P450 2C19 (CYP2C19) and CYP2D6 are important xenobiotic metabolic enzymes and both show considerable genetic variability between Orientals and Caucasians. There are known marked heterogeneity in susceptibility to various cancers and hypertension among Chinese Mongolian, Hui and Han ethnic groups, but the molecular mechanisms are unknown. Our objective was to investigate the patterns of distribution of CYP2C19 and CYP2D6 polymorphisms among healthy Chinese subjects to determine whether any observed inter-ethnic variability might be worth further investigation as possible contributors to the known differences in disease prevalence. Methods: Blood samples were collected from 454 unrelated Chinese healthy subjects (214 Han, 111 Hui, 129 Mongolian) for genotyping analysis. The single nucleotide polymorphisms (SNPs) CYP2C19*2 (681G>A in exon 5), CYP2C19*3 (636G>A in exon 4) and CYP2D6*10 (188C>T in exon 1) were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results and Discussion: Significantly higher frequencies of the CYP2C19 poor metabolic genotypes were observed in Chinese Han (18·7%), Chinese Hui (25·0%) and Chinese Mongolian (10·9%) subjects than has been reported for Caucasians (1·7-3·0%, P < 0·01). The prevalent defective allele CYP2C19*2 occurred more frequently in both Chinese Hui (32·4%) and Han (29·7%) than in Chinese Mongolian (18·2%, P < 0·01) subjects. The CYP2C19*2 and CYP2C19*3 defective alleles were significantly more frequent in Chinese Han and Chinese Hui ethnic groups than have been reported for Caucasians (11·1-16·3% and 0-0·2%, P < 0·01). CYP2D6*1/*10 heterozygotes and CYP2D6*10/*10 homozygotes were observed more frequently in Chinese Han (43·1% and 27·2%), Hui (40·6% and 30·7%) and Mongolian subjects (31·3% and 9·6%, both P < 0·01) than have been reported for Caucasians (5·5% and 0·3%, P < 0·01). In Chinese Mongolians, the CYP2D6*10 allele occurred at a frequency (25·2%, P < 0·01) intermediate between those reported for Caucasians and the other two Chinese ethnic populations. What is new and Conclusions: This is first report of interethnic differences in frequencies of functional CYP2C19 and CYP2D6 genes among Chinese Mongolian, Hui and Han populations. These differences may be important in explaining reported inter-ethnic differences in disease prevalence and response to drugs. [ABSTRACT FROM AUTHOR]

Summary What is known and Objective: Interindividual variability in drug responses may be attributable to genetically determined alteration in enzyme activity. In this study, we investigated the association between cytochrome P450 3A4 ( CYP3A4) genetic polymorphisms and post-operative fentanyl requirements. Methods: Patients ( n = 94) scheduled for gynaecological laparotomy received i.v. fentanyl infusion (3 μg/kg/h) after induction of general anaesthesia. Post-operative fentanyl requirements were quantified by using a patient-controlled analgesia and the number of i.v. fentanyl rescue analgesia required were recorded. Pain control was assessed using visual analogue scores (VAS) and fentanyl's adverse effects were documented. CYP3A4*4, CYP3A4*5 and CYP3A4*18 alleles of cytochrome P450 3A4 were identified by polymerase chain reaction-restriction fragment length polymorphism. Differences in fentanyl requirements, VAS scores and adverse effects among the various genotypes were compared. Results and Discussion: No CYP3A4*4 and CYP3A4*5 alleles were detected. Eighty-nine patients (94·7%) were wild-type, five (5·3%) were heterozygous and none was homozygous. No significant difference was demonstrated between the genotype groups in terms of fentanyl consumption, pain control and adverse effects. What is new and Conclusion: CYP3A4*4 and CYP3A4*5 are rare in the Malaysian Malay population. Genetic polymorphism of CYP3A4*18 may not play an important role in influencing postoperative fentanyl requirements. [ABSTRACT FROM AUTHOR]

Summary What is known and Objective: Bone-cancer pain is a common and refractory cancer pain. Opioids, on their own, do not control this type of pain well enough, and co-analgesics are necessary. Methods: Patients with bone metastasis-related pain at Numeric Rating Scale ≥4 were enrolled to this randomized placebo-controlled trial. They had also received morphine or transdermal fentanyl patches for at least 1 week. During the 3-day efficacy phase, patients received placebo or 1-3 tablets of oxycodone/paracetamol (5/325 mg), four times daily for 3 days. All patients kept a daily pain diary. The primary endpoint was the Pain Intensity Difference (PID). Secondary endpoints were cases of breakthrough pain and rescue morphine consumption. Additional analyses included the Short Form-6 Dimensions (SF-6D) quality-of-life scale and a general impression (GI) of patient satisfaction with treatment at the end of the phase. Results and Discussion: Of the 246 patients in the intent-to-treat set, 89·4% completed the 3-day efficacy phase. PIDs were 0·9 and 0·3 in the oxycodone/paracetamol and placebo groups respectively, on day 1 ( P < 0·001), and 1·5 and 0·3 respectively on day 3 ( P < 0·001). Thirty-eight patients in the treatment group, and 58 in the placebo group, suffered breakthrough pain on day 3 ( P < 0·001). The SF-6D score decreased to 21·2 ± 2·5 in the oxycodone/paracetamol group at the end of the phase ( P = 0·001). In the oxycodone/paracetamol group, 67% rated GI as good, very good, or excellent. What is new and Conclusion: Patients with bone-cancer pain, already on opioids, obtain clinically important, additional pain-control, with regular oxycodone/paracetamol dosing. [ABSTRACT FROM AUTHOR]