International Pharmaceutical Abstracts Research Articles

Timing is important in medication administration: a timely review of chronotherapy research

Chronotherapy involves altering the timing of medication administration to improve the overall control of a disease and to minimise treatment side-effects, and is an emerging concept in the field of therapeutics. The aim of this review is to conduct an in-depth analysis of the recent literature in order to identify and evaluate the evidence base for drug chronotherapy. A literature search was conducted in three databases (Medline, Embase, International Pharmaceutical Abstracts) using the search terms "Chronotherapy", "Chronopharmacology", "Chronopharmacokinetics", "Chronopharmacodynamics", "Chronoefficacy", "Chronoformulation", "Morning and Evening", "Morning and Bedtime" and their combinations. The selection criteria for the inclusion of articles in the review included currency (years 2008-Aug 2011), publication in English language, studies done in Humans and non-review articles that pertained to 'drug' therapy. Our search revealed a total of 192 journal articles, of which 41 articles were selected for review. The specific hypothesis for the effectiveness of chronotherapy that was tested in these 41 studies was chronoeffectiveness (n = 34), followed by chronopharmacokinetics (n = 5), chronomodulation (n = 3) and chronopharmacodynamics (n = 2). The findings from two-thirds (n = 27) of the reviewed studies, support the notion of chronotherapy. The review presents the scope of chronotherapy in drug utilization. We believe that the knowledge of chronotherapy is growing and the current research for chronotherapy is promisingly in the conceptualization or early experimental phase. Going forward, chronotherapy studies should also explore genetic, gender and age related differences. Preliminary screening of new drugs for chronotherapeutic potential may be a way of enhancing quality use of medicines.

Alcohol withdrawal and delirium tremens in the critically ill: a systematic review and commentary

Alcohol withdrawal is common among intensive care unit (ICU) patients, but no current practice guidelines exist. We reviewed published manuscripts for prevalence, risk factors, screening tools, prophylactic and treatment strategies, and outcomes for alcohol withdrawal syndrome (AWS) and delirium tremens (DT) in the critically ill. The following databases: PubMed, MEDLINE, Embase, Cochrane Database of Systematic Reviews and Central Register of Controlled Trials, CINAHL, Scopus, Web of Knowledge, pain, anxiety and delirium (PAD) Guidelines REFWORKS, International Pharmaceutical Abstracts and references for published papers were searched. Publications with high or moderate Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Oxford levels of evidence were included. Reported AWS rates range from <1 % in 'all ICU comers' to 60 % in highly selected alcohol-dependent ICU patients. Alcohol dependence and a history of withdrawal are significant risk factors for AWS occurrence. No screening tools for withdrawal have been validated in the ICU. The benefit of alcohol withdrawal prophylaxis is unproven, and proposed regimens appear equivalent. Early and aggressive titration of medication guided by symptoms is the only feature associated with improved treatment outcome. Treatment of AWS is associated with higher ICU complication rates and resource utilization. The optimal means of identification, prevention and treatment of AWS in order to establish evidence-based guidelines remain to be determined.

Medicine use and medicine-related problems experienced by ethnic minority patients in the United Kingdom: a review

The aim of this review was to establish type(s) and possible cause(s) of medicine-related problems (MRPs) experienced by ethnic minorities in the UK and to identify recommendations to support these patients in the effective use of medicines. A systematic search of studies related to problems with medicine use experienced by ethnic minorities in the UK was performed using the following databases: PubMed, Embase, International Pharmaceutical Abstract and Scopus from 1990 to 2011. A hand search for relevant citations and key journals was also performed. Fifteen studies were found. The MRPs identified across studies included lack of information, problems with not taking medicines as advised, concern of dependency or side effects, lack of regular monitoring and review, risk of adverse drug reactions, adverse events and problems in accessing healthcare services. Many problems are common in other groups, however, studies examining possible explanatory factors discussed how the cultural and religious beliefs, previous experiences, different expectations, language and communication barriers, lack of knowledge of the healthcare services and underestimating patients' desire for information may contribute to the problems. Some of the recommendations were made based on the problems that were found, but these have not been evaluated. Little evidence is known of what influences MRPs among ethnic minorities, despite the increased diversification of populations in countries throughout the world. To support their entire populations in the use of medicines, we have to ensure that we understand their different perspectives and needs regarding the effective use of medicines.

Black cohosh (Cimicifuga spp.) for menopausal symptoms.

Menopause can be a distressing and disruptive time for many women, with many experiencing hot flushes, night sweats, vaginal atrophy and dryness. Postmenopausal women are also at increased risk of osteoporosis. Interventions that decrease the severity and frequency of these menopausal symptoms are likely to improve a woman's well-being and quality of life. Hormone therapy has been shown to be effective in controlling the symptoms of menopause; however, many potentially serious adverse effects have been associated with this treatment. Evidence from experimental studies suggests that black cohosh may be a biologically plausible alternative treatment for menopause; even so, findings from studies investigating the clinical effectiveness of black cohosh have, to date, been inconsistent. To evaluate the clinical effectiveness and safety of black cohosh (Cimicifuga racemosa or Actaea racemosa) for treating menopausal symptoms in perimenopausal and postmenopausal women. Relevant studies were identified through AARP Ageline, AMED, AMI, BioMed Central gateway, CAM on PubMed, CINAHL, CENTRAL, EMBASE, Health Source Nursing/Academic edition, International Pharmaceutical Abstracts, MEDLINE, Natural medicines comprehensive database, PsycINFO, TRIP database, clinical trial registers and the reference lists of included trials; up to March 2012. Content experts and manufacturers of black cohosh extracts were also contacted. All randomised controlled trials comparing orally administered monopreparations of black cohosh to placebo or active medication in perimenopausal and postmenopausal women. Two review authors independently selected trials, extracted data and completed the 'Risk of bias' assessment. Study authors were contacted for missing information. Sixteen randomised controlled trials, recruiting a total of 2027 perimenopausal or postmenopausal women, were identified. All studies used oral monopreparations of black cohosh at a median daily dose of 40 mg, for a mean duration of 23 weeks. Comparator interventions included placebo, hormone therapy, red clover and fluoxetine. Reported outcomes included vasomotor symptoms, vulvovaginal symptoms, menopausal symptom scores and adverse effects. There was no significant difference between black cohosh and placebo in the frequency of hot flushes (mean difference (MD) 0.07 flushes per day; 95% confidence interval (CI) -0.43 to 0.56 flushes per day; P=0.79; 393 women; three trials; moderate heterogeneity: I(2) = 47%) or in menopausal symptom scores (standardised mean difference (SMD) -0.10; 95% CI -0.32 to 0.11; P = 0.34; 357 women; four trials; low heterogeneity: I(2) = 21%). Compared to black cohosh, hormone therapy significantly reduced daily hot flush frequency (three trials; data not pooled) and menopausal symptom scores (SMD 0.32; 95% CI 0.13 to 0.51; P=0.0009; 468 women; five trials; substantial heterogeneity: I(2) = 69%). These findings should be interpreted with caution given the heterogeneity between studies. Comparisons of the effectiveness of black cohosh and other interventions were either inconclusive (because of considerable heterogeneity or an insufficient number of studies) or not statistically significant. Similarly, evidence on the safety of black cohosh was inconclusive, owing to poor reporting. There were insufficient data to pool results for health-related quality of life, sexuality, bone health, vulvovaginal atrophic symptoms and night sweats. No trials reported cost-effectiveness data. The quality of included trials was generally unclear, owing to inadequate reporting. There is currently insufficient evidence to support the use of black cohosh for menopausal symptoms. However, there is adequate justification for conducting further studies in this area. The uncertain quality of identified trials highlights the need for improved reporting of study methods, particularly with regards to allocation concealment and the handling of incomplete outcome data. The effect of black cohosh on other important outcomes, such as health-related quality of life, sexuality, bone health, night sweats and cost-effectiveness also warrants further investigation.

Effect of Therapeutic Doses of Acetaminophen (up to 4 g/day) on Serum Alanine Aminotransferase Levels in Subjects Consuming Ethanol: Systematic Review and Meta‐analysis of Randomized Controlled Trials

To quantify the effect of therapeutic doses of acetaminophen on serum alanine aminotransferase (ALT) levels in subjects who consumed ethanol. Systematic review of six randomized placebo-controlled trials, of which five were included in a meta-analysis. Subjects included in the meta-analysis were those who consumed ethanol and received acetaminophen in doses up to 4 g/day (551 subjects) or placebo (350 subjects). A comprehensive literature search of the MEDLINE, EMBASE, and International Pharmaceutical Abstracts databases and the Cochrane Central Register of Controlled Trials was performed to identify randomized, placebo-controlled trials that enrolled subjects who consumed ethanol, received acetaminophen in therapeutic doses up to 4 g/day, and had serum ALT level measurements. A total of 184 articles were identified; six articles met all criteria. Five of the six articles reported ALT levels on study day 4 for both groups of subjects who received acetaminophen or placebo. Thus, for the meta-analysis, we used the primary outcome of mean change in serum ALT level from baseline to day 4 in the acetaminophen groups compared with the placebo groups. We found that the difference in mean change from baseline ALT levels between the acetaminophen and placebo groups on day 4 was 0.0 U/L (95% confidence interval -0.2-0.1 U/L). There were no reports of liver dysfunction, liver failure, or death in any of the trials. In randomized, placebo-controlled trials of subjects who consumed ethanol, no elevation of ALT level on study day 4 was noted when subjects ingested up to 4 g/day of acetaminophen.

DARU Journal of Pharmaceutical Sciences; The 2012 report of Editor-in-Chief

DARU Journal of Pharmaceutical Sciences (DARU) is one of the 47 scientific journals of Tehran University of Medical Sciences (TUMS). When the journal was launched in 1991, articles were published in the Persian language; English abstracts were then added in 1995, and finally it completed the transition to publishing in the English language for both abstracts and full-text in early 1999. The main scope of this journal is to serve as a platform for all areas of drug conception, design, manufacturing, classification and assessment. DARU welcomes outstanding studies from basic research to clinical investigations as original papers, systematic reviews, meta-analyses, general reviews, mini-reviews, short communications, and editorials from the global scientific community. DARU considers guidelines provided by International Committee of Medical Journal Editors (http://www.icmje.org), Committee on Publication Ethics (COPE; http://www.publicationethics.org), World Association of Medical Editors (WAME; http://wame.org), and European Association of Science Editors (EASE; http://www.ease.org.uk) and request authors to meet these guidelines in submitting their manuscripts. For clinical trials, this journal requires registration in a public trials registry also. The Editor-in-Chief and the journal DARU are members of these three ethical organizations. The journal is a favorite of many researchers in the field of pharmacy and has been free to all readers in the world since its launch. Initiatives to extend the reach of the journal to readers outside the academic community, framed by DARU policy to promote the discipline of drug fields have been successful, judged by rate of highly cited papers and contribution of scientists in different fields from various departments. Scopus® data (Figures ​(Figures11 and ​and2,2, Table ​Table11 ) indicate that this journal has had both immediate impact and an enduring quality. The 2011 impact factor and h-index of DARU according to ISI Web of Science is 0.625 and 8, respectively. Figure 1 Growth of DARU published papers in Scopus®. Figure 2 Number of citations to DARU published papers in Scopus®. Table 1 List of top 10 most cited articles according to Scopus In early 2012, DARU moved to Springer BioMed Central for publication as an Open Access journal. In the new Open Access model, all articles are freely and permanently accessible online immediately upon publication, without subscription charges or its barriers. Authors of articles published in DARU are the copyright holders of their articles. Following publication in DARU the full-text of each article is deposited immediately and permanently in repositories in e-Depot, the National Library of the Netherlands' digital archive of electronic publications. In Open Access journals, authors are asked to pay article processing charges, of course in DARU, TUMS as the owner of the journal will pay on behalf of authors for the first 3 years of its publishing with Springer BioMed Central and thus all authors are waived in this period of time. The editorial policy of this journal is that all submitted manuscripts are initially examined by the Editor-in-Chief and if passed initial requirements, then one of the Section Editors will be assigned to handle its peer review process. Main initial requirements include novelty of the study and paper, fitting in scope of journal, and full adherence to instruction guideline and ethical principles. Statistics for the year 2012 indicates that until May 24, 2012, a total of 272 submissions were received, of which, 73 entered to peer review process, 32 (44%) were accepted and 41 (56%) were rejected. The average review time has been 23 days. DARU is indexed and abstracted in many abstracting and indexing databases such as ISI Web of Science, PubMed Central, Scopus, Excerpta Medica/EMBASE, Scirus, Directory of Open Access Journals (DOAJ), Biological Abstracts (BIOSIS), EBSCO, Asian Science Citation Network (ASCN), CAB Abstracts, Chemical Abstracts Service (CAS), Free Medical Journals, Global Health, Google Scholar, HINARI, Index Copernicus, Index Medicus for WHO Eastern Mediterranean Region (IMEMR), International Pharmaceutical Abstracts (IPA), Natural Product Extracts (NAPRALERT), Open J-Gate, SIR. Publication as the final important stage of any scientific research is necessary for development of sciences and knowledge of the world. By publication, world scientists talk to each other and share their idea, thoughts, findings, and opinions. The science of pharmacy is not an exclusive and thus we need all scientists of the world to consider this journal as one of their favorite to share their studies with others. The editorial board and managers of this journal try their best to develop knowledge and technology in the field of pharmacy in the globe by adhering higher standards of editing and publication to meet the needs of academics, researchers and professionals.

Frequency of adverse drug reactions in hospitalized patients: a systematic review and meta‐analysis

To perform a comprehensive systematic review of prospective studies about frequency of adverse drug reactions (ADRs) occurring during hospitalization (ADR(In) ), including a thorough study quality assessment, meta-analysis and heterogeneity evaluation. Systematic review of several databases: Pubmed, EMBASE, CINAHL, Cochrane, ISI, International Pharmaceutical Abstracts, Scirus, NHS economic, and others, as well as manual search. Inclusion criteria were: prospective studies (assessing all patients before discharge, by a specialized team, at least once a week); with data about ADRs occurring during hospitalization, using WHO's or similar definition of ADR. Two independent reviewers assessed eligibility criteria, extracted data, and evaluated risk of bias. From 4139 studies initially found, 22 were included. Meta-analysis indicate that ADRs may occur in 16.88% (CI95%: 13.56,20.21%) of patients during hospitalization; however, this estimate has to be viewed with caution because there was significant heterogeneity (I² = 99%). The most significant moderators of heterogeneity were risk of bias, population, ward, and methodology for ADR identification. Low risk of bias studies adjusted for population (pediatric versus adult) had I² = 0%. These data are useful as a broad characterization of in-hospital ADRs and their frequency. However, due to heterogeneity, our estimates are crude indicators. The wide variation in methodologies was one of the most important moderators of heterogeneity (even among studies using intensive monitoring). We suggest criteria to standardize methodologies and reduce the risk of bias.

Shortened Interval between Tetanus Vaccines

To identify the minimum safe interval between tetanus-diphtheria (Td) and tetanus-diphtheria-acellular pertussis (Tdap) vaccines. Literature was retrieved through a review of ImmunoFacts, the Centers for Disease Control and Prevention (CDC) Web site, MEDLINE (1966-February 2012) and International Pharmaceutical Abstracts (1970-February 2012) using the terms Tdap, Td, and interval. In addition, reference citations from publications identified were reviewed. All English-language articles identified from the data sources were evaluated. Studies addressing an interval of 2 years or less between Td and Tdap vaccines were included. Two observational noninferiority studies have evaluated the safety of an interval of 2 years or less. The first involved a school-based immunization program to compare the safety of a single dose of Tdap given 18 months to 9 years after a tetanus and diphtheria toxoid-containing vaccine versus an interval of 10 or more years. Injection site erythema and swelling were increased among participants with shortened intervals between vaccines; however, no serious adverse events, entire limb swelling, or Arthus-like reactions were reported. The second study involved health care workers who received Tdap during a pertussis outbreak with the objective to compare safety of intervals less than 2 years between prior tetanus vaccination and Tdap with intervals 2 years or more. Criteria for noninferiority were met overall between the 2 intervals in terms of moderate and severe injection site reactions. Fever was more common with the shortened interval, as was any redness or any swelling. No serious adverse events were reported among the group with an interval of less than 2 years between vaccine administration. Although well-designed randomized controlled trials are lacking, the current observational evidence and CDC provisional recommendations support a shortened interval between Td and Tdap vaccines to protect health care workers from pertussis. Intervals less than 2 years may be associated with an increased incidence of local injection site reactions.

Tocilizumab for the Treatment of Juvenile Idiopathic Arthritis

To evaluate the pharmacology, clinical efficacy, safety, and role of tocilizumab for the treatment of juvenile idiopathic arthritis. A literature search via MEDLINE through PubMed (1970-December 2011) and International Pharmaceutical Abstracts (1970-December 2011) was performed to identify clinical trials and review articles. The key search terms tocilizumab, anti-interleukin 6, and juvenile idiopathic arthritis were used, with several combinations of terms. Bibliographies of selected articles were examined to identify additional references, and ongoing trials were identified through a review of www.clinicaltrials.gov. Articles were limited to those published in English and studies in humans. Studies included in the review examined pediatric data in systemic and polyarticular juvenile idiopathic arthritis. Background information was obtained through reviews of literature on a wide variety of autoimmune disease states in both adult and pediatric populations. Tocilizumab is Food and Drug Administration-approved for use in patients aged 2 years and older with systemic juvenile idiopathic arthritis. Tocilizumab was superior to placebo in triggering a symptomatic response during Phase 2 and 3 clinical trials. Tocilizumab was determined to be safe, with only a small number of serious adverse drug events occurring within studies. Tocilizumab provides expansion of the available options for the treatment of systemic juvenile idiopathic arthritis, specifically in patients who have not responded to conventional therapies. Tocilizumab is relatively well tolerated and has proven efficacy for up to 52 weeks. Further studies are warranted to determine its utility as a first-line option for systemic juvenile idiopathic arthritis as well as its role within the treatment of polyarticular juvenile idiopathic arthritis.

Assessing the Potential Adverse Consequences of Supplemental Calcium on Cardiovascular Outcomes: Should We Change Our Approach to Bone Health?

To assess cardiovascular risks associated with supplemental calcium use to assist clinicians with evidence-based recommendations for patients who have, or who are at risk for, osteoporosis or osteopenia. Literature was accessed through December 2011 using MEDLINE, Cochrane Library, and International Pharmaceutical Abstracts using the terms calcium compounds and cardiovascular disease. In addition, reference citations from the publications identified were reviewed. All English-language articles were evaluated. Randomized controlled trials, observational studies, and meta-analyses were included. While supplemental calcium and vitamin D have been demonstrated to improve bone mineral density and decrease the risk of fractures, there have been recent reports that calcium supplements may increase the risk for cardiovascular events. Nine clinical trials and/or meta-analyses were reviewed; 3 documented increases in cardiovascular risk associated with calcium supplements, and 6 did not. No studies were designed to assess cardiovascular outcomes as primary end points. Balancing the evidence from these analyses with the results of randomized controlled trials assessing the effect of calcium on fracture prevention suggests that the benefits of calcium outweigh the cardiovascular risk. At this time, there is no cause to change routine practice surrounding supplemental calcium use in patients who have, or are at risk for, osteoporosis or osteopenia.

A systematic review of simulated-patient methods used in community pharmacy to assess the provision of non-prescription medicines

To explore the use of simulated-patient methods in community pharmacy for non-prescription medicines. The databases IPA (International Pharmaceutical Abstracts), EMBASE and MEDLINE were searched for articles published between 1990 and 2010 outlining studies using simulated-patient methods. Thirty studies from 31 articles were reviewed. The majority used simulated-patient methods to purely assess counselling behaviour of pharmacy staff, rather than as an opportunity to provide educational feedback to improve counselling behaviour. Few simulated-patient studies have incorporated performance feedback to encourage behavioural change and improve counselling skills. Studies that incorporated feedback did not provide sufficient detail, and few studies have explored participant perceptions. Additionally, very few studies have employed scenarios involving children's medicines. Future studies should test the feasibility of using the simulated-patient method, with appropriate performance feedback and describe participant perceptions of the value and acceptability of this training method.

An analysis of quality of systematic reviews on pharmacist health interventions

In the past 20 years, many studies have evaluated the impact of pharmaceutical practices on clinical, humanistic and economic outcomes. However, few studies have critically analysed the primary studies and published reviews regarding pharmaceutical practices. The aim of this review is to assess the quality of systematic reviews and meta-analysis on pharmacist health interventions published from 1990 to 2009. The data sources used were MEDLINE, Cochrane Library, International Pharmaceutical Abstracts, Latin American and Caribbean Health Sciences, Scientific Electronic Library Online, and Scopus. Studies in which interventions were done by a pharmacist or in which the pharmacist was a health team member were included. There were no restrictions based on the type of intervention, country or languages. The data extracted by two independent reviewers were the following: publication journal, language, publication year, search strategy, study design, quality assessment of the included studies, disease, study settings, intervention description, and outcome measures. The methodological quality of systematic reviews was accessed with AMSTAR. A total of 151 articles were found from which 31 were included. An increase in the number of publications occurred after 2005. Nineteen reviews evaluated the quality of primary studies, and 6 of these reviews performed meta-analyses. The methodological quality of reviews was considered to be moderate (52.8 ± 22.3% for reviewer #1 and 54.8 ± 16.5% for reviewer #2); of the 31 included reviews, 7, 18 and 6 reviews had high, moderate and poor quality, respectively. The quality of published reviews varies from moderate to poor. Improvements in the study design can be achieved by following specific recommendations, such as clearly describing the methods, performing the data extraction in duplicate, researching at least two databases, listing the included and excluded studies, employing tables with the main studies data and evaluating and reporting the scientific quality of the included articles.

Takotsubo Cardiomyopathy as a Complication of Electroconvulsive Therapy

To examine the evidence regarding takotsubo cardiomyopathy as a complication of electroconvulsive therapy (ECT). Searches in MEDLINE, EMBASE, and International Pharmaceutical Abstracts (1966-August 2011) were conducted. Published studies and case reports that mentioned takotsubo cardiomyopathy following ECT were reviewed. Twelve case reports were available for review. There were 7 documented cases of takotsubo cardiomyopathy, 4 cases of myocardial stunning, and 1 case of cardiogenic shock following ECT. Although takotsubo cardiomyopathy was not mentioned in 5 of the cases, some clinical characteristics were consistent with this diagnosis. Left ventricular ejection fraction and the electrocardiogram returned to normal within a few days in the majority of the cases. All cases were in women, the majority of whom were postmenopausal (average age 64 years). Takotsubo cardiomyopathy developed after a single course of ECT in 6 of the cases, while the syndrome developed after more than 1 course in the other 6 cases. ECT was successfully readministered without syndrome recurrence in 4 of the cases, but only after 3 of the 4 patients received a β-adrenergic receptor blocking agent prior to each subsequent therapy session. The β-adrenergic blocking agents used were esmolol in 1 case and labetolol in the other 2. Takotsubo cardiomyopathy is a serious but transient potential complication of electroconvulsive therapy. Limited evidence indicates that β-adrenergic receptor blocking agents may help prevent its reoccurrence in patients needing further electroconvulsive treatment. Health care providers in psychiatry should be aware of this potential complication of electroconvulsive therapy, especially in postmenopausal women. However, many questions remain regarding this issue.

Drug-Induced Yawning—A Review

To review the current literature on drug-induced yawning. Literature was accessed through MEDLINE/PubMed (1996-July 2011), International Pharmaceutical Abstracts (1997-July 2011), and EMBASE, using the search terms yawning, drug-induced yawning, and adverse drug reactions. Relevant clinical trials and case reports were selected and included to present background information. Bibliographies of all relevant articles were reviewed for additional citations. Yawning is a common stereotype behavior with unknown physiologic function that occurs in most vertebrates and humans as early as 15 weeks of intrauterine life. Yawning is under the control of several neurotransmitters and neuropeptides, including dopamine, serotonin, oxytocin, and acetylcholine. Among drugs, antidepressants, opioids, dopaminergic agents, benzodiazepines, and induction agents are the main pharmacologic classes associated with yawning. Yawning is rarely a serious adverse reaction and is not frequently listed in the drug summary. Most available data are based on case reports, small studies, and older literature. Clinicians should be aware of the agents commonly triggering this behavior.

Association of HLA-B*5801 allele and allopurinol-induced stevens johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis

BackgroundDespite some studies suggesting a possible association between human leukocyte antigen, HLA-B*5801 and allopurinol induced Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), the evidence of association and its magnitude remain inconclusive. This study aims to systematically review and meta-analyze the association between HLA-B*5801 allele and allopurinol-induced SJS/TEN.MethodsA comprehensive search was performed in databases including MEDLINE, Pre-MEDLINE, Cochrane Library, EMBASE, International Pharmaceutical s (IPA), CINAHL, PsychInfo, the WHO International, Clinical Trial Registry, and ClinicalTrial.gov from their inceptions to June 2011. Only studies investigating association between HLA-B*5801 with allopurinol-induced SJS/TEN were included. All studies were extracted by two independent authors. The primary analysis was the carrier frequency of HLA-B*5801 comparison between allopurinol-induced SJS/TEN cases and each comparative group. The pooled odds ratios were calculated using a random effect model.ResultsA total of 4 studies with 55 SJS/TEN cases and 678 matched-controls (allopurinol-tolerant control) was identified, while 5 studies with 69 SJS/TEN cases and 3378 population-controls (general population) were found. SJS/TEN cases were found to be significantly associated with HLA-B*5801 allele in both groups of studies with matched-control (OR 96.60, 95%CI 24.49-381.00, p < 0.001) and population-control (OR 79.28, 95%CI 41.51-151.35, p < 0.001). Subgroup analysis for Asian and Non-Asian population yielded similar findings.ConclusionWe found a strong and significant association between HLA-B*5801 and allopurinol-induced SJS/TEN. Therefore, HLA-B*5801 allele screening may be considered in patients who will be treated with allopurinol.

Cochrane Review: Minocycline for acne vulgaris: efficacy and safety

Cochrane Review: Minocycline for acne vulgaris: efficacy and safety

Assessing Evidence of Interaction Between Smoking and Warfarin: A Systematic Review and Meta-analysis

Chronic smoking, theoretically, can interfere with warfarin metabolism through enzyme-inducing effects of polycyclic aromatic hydrocarbons. However, clinical evidence of interactions between warfarin and smoking are inconclusive. This study aimed to systematically review all relevant clinical evidence of this interaction. We performed a systematic search using computerized databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, CINAHL, Allied and Complementary Medicine, PsycINFO, International Pharmaceutical Abstracts, and ClinicalTrials.gov from 1966 to December 2008. Keywords included "warfarin" with "smoking," "tobacco," "cigarette," and "polycyclic aromatic hydrocarbons." Original articles reporting interaction between warfarin and smoking were included. All articles were reviewed independently by two investigators for study design, population, outcomes, and quality of evidence. Of the 1,240 studies retrieved, one experimental pharmacokinetic study and 12 cross-sectional studies were included. The pooled analyses of multivariate studies suggested that smoking was associated with a 12.13% (95% CI, 6.999-17.265; P < .001) increase in warfarin dosage requirement and an additional 2.26 mg (95% CI, 2.529-7.042; P = .355) per week compared with nonsmoking. Additional sensitivity analysis of four multivariate studies with adjustment for pharmacogenomic factors suggested that smoking was associated with a 13.21% (95% CI, 8.59%-17.83%; P < .001) increase in warfarin dosage requirement compared with nonsmokers. Results of an experimental pharmacokinetic study lend theoretical support to the findings. Evidence suggests that smoking may potentially cause significant interaction with warfarin by increasing warfarin clearance, which leads to reduced warfarin effects. Close monitoring of warfarin therapy should be instituted when there is a change in smoking status of patients requiring warfarin therapy.

Ceftaroline Fosamil&amp;mdash;A New Broad-Spectrum Cephalosporin with Significant Activity against Methicillin-Resistant Staphylococci

Ceftaroline fosamil (PPI-0903, TAK-599, Teflaro®, Forest Pharmaceuticals) is the prodrug for ceftaroline (T-91825), a broad-spectrum parenteral (IM/IV) cephalosporin with potent in vitro and in vivo activity against methicillin- and vancomycin-resistant staphylococci as well as other common pathogens of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CAP). Although more active than other cephalosporins against enterococci, the potency of this agent is still modest against E. faecalis (inactive vs. E. faecium). It is also active against Enterobacteriaceae with the exceptions of strains producing extended-spectrum beta-lactamases or carbapenemases. It is also active against anaerobic organisms with the exceptions of Bacteroides and Prevotella species and Clostridium difficile. Ceftaroline fosamil is non-inferior compared with regimens of vancomycin with/without aztreonam (ABSSSI) and ceftriaxone (CAP). The usual dosage regimen is 600 mg every 12 hours, as a 1-hour IV infusion, with dosage adjustment in moderate renal impairment (creatinine clearance [CrCl] of 31–50 mL/min) to 400 mg every 12 hours, in severe renal impairment (CrCl 15–30 mL/min) to 300 mg every 12 hours, and in end-stage renal impairment/hemodialysis (CrCl < 15 mL/min) to 200 mg every 12 hours. Further studies continue with a combination product of ceftaroline fosamil with NXL104 (a beta-lactamase inhibitor). This paper will review the chemistry, mechanism of action, in vitro and in vivo (animal) antibacterial activity, pharmacokinetics, clinical efficacy, tolerability, dosing and administration, and role of this agent. Medline/PubMed, International Pharmaceutical Abstracts, and EMBASE databases were searched for relevant articles using the search terms “ceftaroline”, “PPI-0903”, “TAK-599”, and “T-91825”. All English and French language articles identified in the searches were reviewed for their relevance to this review. In addition, the bibliographies of retrieved articles were reviewed to identify any relevant articles not identified in the initial searches. Also, the proceedings of all Interscience Conferences on Antimicrobial Agents and Chemotherapy (American Society for Microbiology) from 2000 through 2010 were searched for relevant abstracts.

Clinical applications of pharmacogenomics guided warfarin dosing

To assess the state of the literature concerning pharmacogenomic testing in patients requiring vitamin K antagonists, specifically warfarin. We conducted a literature search of MEDLINE and International Pharmaceutical Abstracts using the following words: warfarin, pharmacogenetic, and pharmacogenomic. The search results were reviewed by the authors and papers concerning pharmacogenomic testing in warfarin dosing were procured and reviewed. Additionally bibliographies of papers procured were also examined for other studies. The authors focused on clinical trials concerning the use of pharmacogenomic testing in warfarin dosing. Although numerous studies have demonstrated that a significant portion of warfarin dosing variability can be explained by genetic polymorphisms, few prospective studies have been conducted that examine the integration of this information in practical dosing situations. Those that have, have shown that using pharmacogenomic information improves initial dosing estimates and decreases the need for frequent clinic visits and laboratory testing. Data showing a reduction in serious bleeding events is sparse. Cost-effectiveness analyses have generally shown a small but positive effect with pharmacogenomic testing in patients receiving warfarin. Several studies have shown that pharmacogenomic testing for warfarin dosing is more accurate that other dosing schemes. Pharmacogenomic testing improves time to a therapeutic international normalized ratio while requiring fewer dosing adjustments. Patients who require higher or lower than usual doses seem to benefit the most. The cost-effectiveness of pharmacogenomic testing as well as preventing of outcomes such as bleeding or thrombosis are not yet elucidated. Pharmacists, especially those in a community setting can play a role in this new technology by educating prescribers and patients concerning pharmacogenomic testing, and by developing and using dosing protocols that incorporate its use.

Risk of Hepatic Events in Patients Treated with Vancomycin in Clinical Studies

Routine surveillance of spontaneous reporting data and subsequent disproportionality analyses have indicated that the use of vancomycin might be associated with an increased risk of hepatic events. To conduct a meta-analysis of published randomized controlled clinical trials (RCTs) to better understand if the use of vancomycin is potentially associated with an increased risk of hepatic events. A comprehensive search and review of published clinical studies indexed in MEDLINE, PubMed, International Pharmaceutical Abstracts and the Cochrane Library from 1950 to June 2010 was conducted. The inclusion criteria consisted of (i) published RCTs comparing vancomycin with/without other additional treatments to other comparators; and (ii) studies that reported hepatic events. The data related to any hepatic events reported in RCTs were extracted and examined. The quality of selected studies was assessed based on the Jadad scale. The effect size was presented as a risk ratio (RR) with a 95% CI and number needed to harm. The pooled RRs were calculated by using both fixed-effects and random-effects models. The impact of publication bias was assessed by funnel plot and the Egger's test. A total of 20 RCTs, including 7419 patients, met the study inclusion criteria and were selected. An increased incidence of hepatic events, specifically elevated serum aminotransferase levels, was observed in patients receiving vancomycin, when compared with other comparators (pooled RR=1.95; 95% CI 1.62, 2.36; p<0.001), but the majority of the events were mild to moderate in nature. No evidence is currently available suggesting that the use of vancomcycin confers a risk of progressive or severe drug-induced liver injury. Continuous monitoring of hepatic events on a routine basis among patients with the use of vancomycin is suggested.