Comparison of entecavir and lamivudine in preventing HBV reactivation in lymphoma patients undergoing chemotherapy: a meta-analysis

Background Multiple studies have compared the efficacy of entecavir with lamivudine in preventing hepatitis B virus (HBV) reactivation among HBV-carrying lymphoma patients with chemotherapy treatment. However, the results were slightly varied. Aim of the review to combine the findings of independent studies assessing the clinical efficacy of the two drugs using a systematic review and meta-analysis. Methods PubMed, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Chongqing VIP and WanFang Data were retrieved. Two independent reviewers evaluated the study eligibility and extracted eight studies, with 770 patients in total. The meta-analysis was conducted using RevMan 5.3 and STATA software. Results HBV-carrying lymphoma patients receiving lamivudine during chemotherapy had a statistically significantly higher odds of HBV reactivation compared to those receiving entecavir (OR 5.0, 95 % CI 2.85–8.78, P < 0.001). The odds of hepatitis, HBV-Reactivation caused hepatitis and chemotherapy disruption was statistically significantly elevated in the patient group receiving lamivudine compared to the entecavir group (OR 4.12, 95 % CI 1.70–9.98, P = 0.002; OR 11.44, 95 % CI 2.70–48.52, P < 0.001; OR 6.71, 95 % CI 2.34–19.26, P < 0.001, respectively). Furthermore, the HBV reactivation rate in Ann Arbor stages I - II patient group was statistically significantly lower than the one in Ann Arbor stages III–IV group, with an overall pooled value of 0.37 (95 % CI 0.17–0.82, P = 0.01). Conclusion The metaanalysis result suggested that among HBV-carrying lymphoma patients undergoing chemotherapy, entecavir is more effective than lamivudine in preventing HBV reactivation.     

Preventive effect of pre-warming,hot compress,and pH adjustment in oxaliplatin-induced venous pain

Background Venous pain induced by peripheral intravenous administration of oxaliplatin remains clinically unresolved. Objective The aim of this study was to determine the efficacy of comprehensive intervention care for venous pain in colorectal cancer patients receiving oxaliplatin. Setting A Japanese tertiary hospital. Method We treated all outpatients after April 2012 with comprehensive intervention care including pre-warming of the oxaliplatin solution, use of a hot compress, and pH adjustment by combination with dexamethasone. We retrospectively reviewed the electronic medical records from colorectal cancer patients who had received oxaliplatin via a peripheral vein between December 2009 and June 2014. Main outcome measures The primary endpoint of this study was the incidence of venous pain at the administration site during oxaliplatin infusion, according to injection site reaction grade ≥ 2. Results We evaluated 271 treatment courses in 59 patients. Venous pain occurred in 42 courses (15.5%) among 26 patients. Multivariate logistic regression analysis revealed that female gender and body mass index ≥ 25 kg/m² were significantly associated with an increased risk of venous pain during all courses (adjusted odds ratio [OR]: 3.18, 95% confidence interval [CI] 1.35–7.92; P < 0.01; and adjusted OR: 3.37, 95% CI 1.26–9.40; P = 0.02, respectively), whereas comprehensive intervention care were significantly associated with reduced risk of venous pain during all courses (adjusted OR: 0.10, 95% CI 0.02–0.44; P < 0.01). Conclusion Comprehensive intervention care is a clinical treatment option for oxaliplatin-induced peripheral venous pain in patients with colorectal cancer, especially females with obesity.     

Impact of pharmaceutical care on cardiovascular risk among older HIV patients on antiretroviral therapy

Background Advances in the treatment of HIV infection have enabled better control of the disease, allowing patients to enjoy a longer life expectancy. However, the ageing of patients leads to an increased prevalence of cardiovascular disease. Various studies have found that pharmaceutical care results in better control of cardiovascular risk factors. Objective To measure the impact of pharmaceutical care on cardiovascular risk in patients older than 50 years receiving combination antiretroviral therapy. Setting Outpatient pharmacy service of a tertiary hospital, Spain. Methods A pre/post-intervention quasi-experimental clinical study was conducted in which health education and pharmacist interventions to reduce cardiovascular risk factors were carried out in a single patient cohort using the Dader method of pharmacotherapy, with a 12-month follow-up period per patient. Patients included were older than 50 years, with moderate/elevated cardiovascular risk. Data were obtained from patient clinical histories, dispensing records and patient interviews, and were subjected to statistical analysis. Main outcome measure Cardiovascular risk estimated by SCORE and REGICOR equations. Results Forty-two patients completed the study. Of these, 93 % were men, with an average age of 57 years and 15 years since diagnosis of HIV. A reduction was observed in the mean values (baseline vs. 12 months) of the following cardiovascular risk factors: systolic blood pressure (P = 0.009), diastolic blood pressure (P = 0.010), total cholesterol (P = 0.006), low-density lipoprotein cholesterol (LDL-c; P = 0.039), triglycerides (P = 0.010) and total cholesterol/high-density lipoprotein cholesterol (HDL-c; P < 0.001). An increase in HDL-c (P = 0.037) was also observed. The average cardiovascular risk estimated by the SCORE instrument was reduced from 7.6 % at the beginning of the study to 6.4 % after 12 months (P = 0.039). The risk estimate according to REGICOR also decreased (P = 0.002). Over the 12-month period, 6.3 ± 3.4 interventions were carried out per patient. Quantitative ineffectiveness was the most prevalent negative outcome associated with medication throughout the study, and noncompliance was the most frequent cause. Interventions on health education were the most common, followed by interventions on improving adherence. Conclusion Pharmaceutical care, delivered as a combination of health education and pharmacotherapy follow-up to outpatients at a tertiary hospital, had a positive impact on cardiovascular risk in patients older than 50 years receiving combination antiretroviral therapy.     

Safety of an injection with a mixture of extracts from <Emphasis Type="Italic">Herba Artemisiae annuae</Emphasis>, <Emphasis Type="Italic">Fructus Gardeniae</Emphasis> and <Emphasis Type="Italic">Flos Lonicerae</Emphasis>

Objective This study aimed to evaluate the safety for an injection with a mixture of extracts from Herba Artemisiae annuae, Fructus Gardeniae and Flos Lonicerae and to determine the risk factors that may affect its adverse drug reactions. Methods A drug-oriented prospective observational study was performed. Physicians filled in clinical observation forms with detailed information of the patients including general information, drug information, therapeutic effects and adverse drug events. The adverse drug reaction factors were analyzed by both mono-factor and multiple-factor logistic regression methods. Results From April to July 2007, we collected 12,427 observation forms from 46 hospitals in Jiangsu Province of China. Among the 11,707 observation forms we analyzed, 8,074 patients were children younger than 14 years old (69%). Among 51 reported adverse drug events, 45 cases were adverse drug reactions. The total adverse drug reaction incidence of the injection was 0.38%. While most adverse drug reactions were previously known (e.g., rash, pruritus, vomiting and diarrhea), we observed three new ADR symptoms: shiver, phlebitis and anhelation. All the adverse drug reactions were controlled very well through the follow-up therapy, and none of them was life threatening. The mono-factor analysis showed that adverse drug reactions of the injection were significantly correlated with total medication dose (P = 0.0049) and combination medication (P = 0.0143), especially with antimicrobial drugs (P = 0.0079) and macrolides (P = 0.0017). The multiple factor analysis confirmed these results: medication dosage and combination medication had a crucial impact on adverse drug reactions of the injection; the risk was increased by 24.8% (the estimated value of relative risk was 1.248, 95% confidence interval: 1.054–1.479) and 89% (1.890, 1.001–3.566), respectively. Conclusion The total adverse drug reaction incidence of the injection was 0.38% and lower than we expected. Moreover, we observed three new adverse drug reactions, none of which was severe.     

<Emphasis Type="Italic">CYP2D6*4</Emphasis>, <Emphasis Type="Italic">CYP3A5*3</Emphasis> and <Emphasis Type="Italic">ABCB1 3435T</Emphasis> polymorphisms and drug-related falls in elderly people

Objective The objective of this study is to investigate the association between CYP2D6*4, CYP3A5*3 and ABCB1 3435T polymorphisms and drug-related falls. Method Multivariate logistic regression was performed in an existing database in order to study the association between falls history and CYP2D6*4, CYP3A5*3, ABCB1 3435T polymorphisms in patients using fall-risk-increasing CYP2D6, CYP3A5 and P-glycoprotein (gene product of ABCB1) substrates. Results No statistically significant increased fall risk was found in ‘poor metabolizers’ compared to ‘extensive’ and ‘intermediate metabolizers’ using fall-risk-increasing CYP2D6 substrates (Odds ratio (OR) = 2.2; 95% confidence interval (CI) 0.2–25.0), CYP3A5 substrates (OR = 0.9; 95% CI 0.2–3.3) and P-glycoprotein substrates (OR = 2.1; 95% CI 0.2–17.2). Conclusion The hypothesis that ‘poor metabolizers’ have an increased fall risk was not confirmed. A larger study population is needed to confirm the potential association that was seen between CYP2D6*4 and ABCB1 3435T polymorphisms and drug-related falls.     

Factors that affect adverse drug reaction reporting among hospital pharmacists in Western China

Background Hospital pharmacists can make a considerable contribution to the spontaneous reporting system of adverse drug reactions. The factors that influence adverse drug reaction reporting among hospital pharmacists remain largely unknown in China. Objective This study aims to identify factors that affect hospital pharmacist-led adverse drug reaction reporting in Xi’an, and to obtain suggestions from pharmacists about how to improve the current adverse drug reaction reporting system. Setting Hospital settings throughout Xi’an, a region of Western China. Method A matched case–control study was conducted on a population of 2,814 hospital pharmacists in Xi’an during 2011. Cases included all pharmacists who had reported at least one adverse drug reaction between 2008 and 2010 and agreed to participate in the study (186/204; 91.2 %); controls (n = 372) were pharmacists who had not reported any adverse drug reaction during the same period. A self-administered questionnaire was distributed to the participants. Logistic regression was performed to evaluate the association between indicator variables and the outcome of having reported at least one adverse drug reaction. Main outcome measure Pharmacists’ knowledge, attitude and practice towards adverse drug reaction reporting and factors affecting reporting. Results Higher professional title (adjusted OR 1.44; 95 % CI 1.07–1.94; p = 0.018), having received training about adverse drug reaction reporting (1.64; 1.04–2.57; p = 0.032), better knowledge about reporting (1.53; 1.12–2.08; p = 0.007), “lack of access to adverse drug reaction reporting form” (0.29; 0.12–0.72; p = 0.008) was independently associated with adverse drug reaction reporting. Clinical pharmacists were more likely to report an adverse drug reaction than dispensary pharmacists (1/adjusted OR 5.26; p < 0.001), pharmacy administrators (5.00; p = 0.003), and other technicians (5.56; p = 0.001). Conclusions Higher professional title, having received training, mastering knowledge about reporting, and being a clinical pharmacist were positive predictors of pharmacist-led adverse drug reaction reporting. Lack of access to reporting forms was a negative predictor. Continuous training and establishing incentive mechanisms are needed to promote adverse drug reaction reporting among hospital pharmacists.     

Effects of <Emphasis Type="Italic">CYP2C9</Emphasis> genetic polymorphisms on the pharmacokinetics of celecoxib and its carboxylic acid metabolite

Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, is used for the treatment of rheumatoid arthritis and osteoarthritis. The predominant hepatic metabolism of celecoxib to celecoxib carboxylic acid (CCA) is mediated mainly by CYP2C9. We investigated the effects of the major CYP2C9 genetic variants in Asian populations, CYP2C9*3 and CYP2C9*13, on the pharmacokinetics of celecoxib and its carboxylic acid metabolite in healthy Korean subjects. A single 200-mg oral dose of celecoxib was given to 52 Korean subjects with different CYP2C9 genotypes: CYP2C9EM (n = 26; CYP2C9*1/*1), CYP2C9IM (n = 24; CYP2C9*1/*3 and *1/*13), and CYP2C9PM (n = 2; CYP2C9*3/*3). Celecoxib and CCA concentrations in plasma samples collected up to 48 or 96 h after drug intake were determined by HPLC–MS/MS. The mean area under the plasma concentration–time curve (AUC_0–∞) of celecoxib was increased 1.63-fold (P < 0.001), and the apparent oral clearance (CL/F) of celecoxib was decreased by 39.6% in the CYP2C9IM genotype group compared with that of CYP2C9EM (P < 0.001). The overall pharmacokinetic parameters for celecoxib in CYP2C9*1/*13 subjects were similar to those in CYP2C9*1/*3 subjects. Two subjects with CYP2C9PM genotype both showed markedly higher AUC_0–∞, prolonged half-life, and lower CL/F for celecoxib than did subjects with CYP2C9EM and IM genotypes. CYP2C9*3 and CYP2C9*13 variant alleles significantly affected the plasma concentration of celecoxib.     

Levetiracetam versus phenytoin for seizure prophylaxis in brain injured patients: a systematic review and meta-analysis

Background The onset of early and/or late seizures in brain injured patients is associated with worse outcome. So far, phenytoin is the most commonly used antiepileptic drug to prevent seizures in this group of patients. Objective In the current metaanalysis, we aimed to compare the efficacy and safety of phenytoin versus levetiracetam for seizure prophylaxis in brain injured patients. Methods A systematic search was conducted in PubMed and Cochrane Library Database by 2 investigators. Four randomized controlled trials (RCTs) were included (295 patients). Data were extracted and the quality of each RCT was assessed. Results Levetiracetam was found to be more effective than phenytoin in seizure prophylaxis (OR = 0.23; CI 95% [0.09–0.56]; Q test p value = 0.18 and I² = 38%). A trend toward less serious side effects was also found in patients treated with levetiracetam (OR = 0.27; CI 95% [0.07–1.07]; Q test p value = 0.72 and I² = 0%). Conclusion Levetiracetam is more effective and safer than phenytoin for seizure prophylaxis in brain injured patients.     

Chemical composition and bioactivities of the essential oil from different organs of <Emphasis Type="Italic">Ferula communis</Emphasis> L. growing in Tunisia

The essential oils obtained by the hydrodistillation from the fresh flowers, leaves, stems, and roots of Ferula communis L., growing in Tunisia were analyzed by GC and GC/MS. Thirty-two components were identified in the oil of flowers with camphor (18.3 %), α-pinene (15.3 %), and β-eudesmol (9.3 %) as the main constituents. Twenty-nine compounds were identified in the oil of stems with β-eudesmol (28.1 %), δ-eudesmol (11.1 %), and α-eudesmol (9.6 %) as the main compounds. Twenty compounds were characterized in the oil of roots with dillapiole (7.9 %), guaiol (7.3 %), and spathulenol (6.8 %). In the oil of leaves, α-eudesmol (25.2 %), β-eudesmol (20.7 %), δ-eudesmol (10.1 %), and caryophyllene oxide (7.2 %) were found as the main constituents. This study was undertaken to evaluate the antioxidant activity using DPPH (2,2′-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid), reducing power, and catalase activity. We tested also the antibacterial, cytotoxic, and cholinesterase inhibition properties of the essential oil of different organs of F. communis. The essential oil of the stems showed the highest antioxidant activity (IC₅₀ = 0.03 ± 0.001 mg mL^?1), in DPPH assay and the important result of catalase (303.03 µmol H₂O₂ degraded/min/protein) of F. communis. The antibacterial activity of the oil was determined by micro-well dilution assay. The best results (MIC = 0.156 ± 0.02 mg mL^?1) were exhibited by the essential oil of the leaves of F. Communis against Pseudomonas aeruginosa. Besides, the strongest cytotoxic activity against Hela cells was shown with essential oils’ leaves with an inhibition percentage of 79.05 % at the concentration of 500 µg mL^?1. However, the best inhibition percentage of A 549 cells was detected for essential oils’ leaves with an inhibition percentage of 54.56 % at 250 µg mL^?1. Our finding showed that the essential oil of the flowers was the most active, with 64.623 % of inhibition against butyrylcholinesterase at 10 mg mL^?1 from the incubation time of 30 min.     

Effect of Cd<Superscript>+2</Superscript> on phosphate solubilizing abilities and hydrogen peroxide production of soil-borne micromycetes isolated from <Emphasis Type="Italic">Phragmites australis</Emphasis>-rhizosphere

The aims of this work were to evaluate the phosphate-solubilization and hydrogen peroxide (H₂O₂) production by the soil-borne micromycetes, Aspergillus japonicus, Penicillium italicum and Penicillium dipodomyicola, isolated from Phragmites australis rhizosphere and to study the effect of several concentrations of Cadmium (Cd²⁺) on both variables. Our results showed that P. italicum achieved a higher P-solubilization and H₂O₂ production than A. japonicus and P. dipodomyicola, as only P. italicum showed a positive correlation (R² = 0.71) between P-solubilization and H₂O₂ production. In dose–response assays, P. italicum was also more tolerant to Cd²⁺ (0.31 mM) in comparison to A. japonicus (0.26 mM). Analysis of the 2⁴ factorial experimental design showed that P-solubilization by P. italicum was negatively affected by increases in Cd²⁺ (p = 0.04) and yeast extract (p = 0.02) in the culture medium. The production of H₂O₂ was positively affected only by glucose (p = 0.002). Fungal biomass production was reduced significantly (p = 0.0009) by Cd²⁺ and increased (p = 0.0003) by high glucose concentration in the culture medium. The tolerance and correlation between P-solubilization and H₂O₂ production in the presence of Cd²⁺ was strain and species dependent. The effects of Cd²⁺, glucose, ammonium sulfate and yeast extract on those variables were evaluated through a two-level factorial design. P. italicum is promising for P-solubilization in soils contaminated with Cd²⁺ and may be an alternative for manufacture of biofertilizers to replace chemical fertilizers.     

Bacterial Meningitis in Patients using Immunosuppressive Medication: a Population-based Prospective Nationwide Study

We studied occurrence, presentation, disease course, effect of adjunctive dexamethasone, and prognosis of bacterial meningitis in patients using immunosuppressive medication. Patients were selected from our nationwide, prospective cohort on community-acquired bacterial meningitis performed from March 1, 2006 through October 31, 2014. Eighty-seven of 1447 episodes (6 %) of bacterial meningitis occurred in patients using immunosuppressive medication, and consisted of corticosteroids in 82 %. Patients with bacterial meningitis using immunosuppressive medication were less likely to present with headache (P = 0.02) or neck stiffness (P = 0.005), as compared those not on immunosuppressive medication. In 46 % of episodes CSF leukocyte count was below 1000/mm³. CSF cultures revealed S. pneumoniae in 41 % and L. monocytogenes in 40 % of episodes. Outcome was unfavorable in 39 of 87 episodes (45 %) and death occurred in 22 of 87 episodes (25 %). Adjunctive dexamethasone was administered in 52 of 87 (60 %) episodes, and mortality tended to be lower in those on adjunctive dexamethasone therapy as compared to those without dexamethasone therapy (10 of 52 [19 %] vs 12 of 35 [34 %], P = 0.14). We conclude that bacterial meningitis in patients using immunosuppressive medication is likely to present with atypical clinical and laboratory features, and is often caused by atypical bacteria, mainly L. monocytogenes. Adjunctive dexamethasone is widely prescribed in these patients and was not associated with harm in this study.     

Multivessel Revascularization Does Not Increase Contrast-Induced Acute Kidney Injury Incidence in Acute Myocardial Infarction: A Meta-Analysis

Background

Recent studies and meta-analysis have shown that complete revascularization (CR) compared with infarct-related artery revascularization (IRA) during percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI) is associated with decreased mortality. However, it is unclear if CR versus IRA in STEMI during indexed hospitalization is associated with risk of contrast-induced acute kidney injury (CI-AKI).

Methods

A database search was conducted for all randomized controlled trials that enrolled STEMI patients and compared CR versus IRA and reported CI-AKI. Comprehensive Meta-Analysis Version 2.0 (Wiley, Chichester) was used to determine summary effect size with a fixed-effect model and expressed as a risk ratio with 95 % confidence intervals.

Results

A total of four trials were identified and had a mean follow-up of 24.5 ± 9.9 months, a total sample size of 1537, a mean age of 63.8 ± 1.2 versus 64.2 ± 2.1 years, 31.2 ± 5.3 versus 30.1 ± 4.7 % three-vessel disease, and 33.7 ± 4.1 versus 37.2 ± 4.5 % anterior STEMI in the CR versus IRA groups, respectively. A total of 276.7 ± 25.2 versus 186.7 ± 15.3 mL contrast was used in the CR versus IRA respectively (p = 0.006). There were no statistical significant differences between the two groups in the reported incidence of CI-AKI (1.3 % CR vs. 1.9 % IRA; p = 0.4), major bleeding (1.7 % CR vs. 2.5 % IRA; p = 0.4) and stroke (1.1 % CR vs. 0.4 % IRA; p = 0.24). However, there was a significantly increased incidence of cardiovascular death (2.0 % CR vs. 4.7 % IRA; p = 0.01) and ischemia-driven revascularization (6.2 % CR vs. 18.3 % IRA; p < 0.01).

Conclusion

In the index hospitalization, CR in STEMI patients is associated with significant risk reduction in cardiac death and revascularization and a non-significant reduced trend of CI-AKI, despite increased use of contrast when compared with IRA.

     

Fosinopril improves the electrophysiological characteristics of left ventricular hypertrophic myocardium in spontaneously hypertensive rats

This study investigated the effects of fosinopril on the electrophysiological characteristics of the left ventricular hypertrophic myocardium in spontaneously hypertensive rats (SHRs). Twenty-four 10-week-old male SHRs were divided into fosinopril and non-fosinopril groups (n?=?12 each). Twelve 10-week-old Wistar–Kyoto rats were used a control group. Left ventricular mass index and ventricular fibrillation threshold (VFT) were measured after 8 weeks of fosinopril or saline treatment. L-type calcium current (I _CaL), sodium current (I _Na), and transient outward potassium current (I _to) were measured in left ventricular myocytes after 8 weeks of fosinopril or saline treatment using the whole-cell patch-clamp technique. VFT was higher in the fosinopril group than in the non-fosinopril group (17.5?±?1.2 mA vs. 15.6?±?1.1 mA, P?<?0.01). The density of I _CaL was lower in the fosinopril group than in the non-fosinopril group (?7.17?±?0.13 pA/pF vs. ?7.87?±?0.13 pA/pF, P?<?0.05). The density of I _to was higher in the fosinopril group than in the non-fosinopril group (14.46?±?0.28 pA/pF vs. 12.66?±?0.25 pA/pF, P?<?0.05). I _to was positively correlated with VFT (r?=?0.90, P?<?0.001) and was found to be associated independently with VFT (P?<?0.001). Fosinopril improves the electrophysiological characteristics of the left ventricular hypertrophic myocardium in SHRs.