Multifaceted Pharmacist‐led Interventions in the Hospital Setting: A Systematic Review

Clinical pharmacy services often comprise complex interventions. In this MiniReview, we conducted a systematic review aiming to evaluate the impact of multifaceted pharmacist‐led interventions in a hospital setting. We searched MEDLINE, Embase, Cochrane Library and CINAHL for peer‐reviewed articles published from 2006 to 1 March 2018. Controlled trials concerning hospitalized patients in any setting receiving patient‐related multifaceted pharmacist‐led interventions were considered. All types of outcome were accepted. Inclusion and data extraction were performed. Study characteristics were collected, and risk of bias assessment was conducted utilizing the Cochrane Risk of Bias tools. All stages were conducted by at least two independent reviewers. The review was registered in PROSPERO (CRD42017075808). A total of 11,896 publications were identified, and 28 publications were included. Of these, 17 were conducted in Europe. Six of the included publications were multi‐centre studies, and 16 were randomized trials. Usual care was the comparator. Significant results on quality of medication use were reported as positive in eleven studies (n = 18; 61%) and negative in one (n = 18, 6%). Hospital visits were reduced significantly in seven studies (n = 16; 44%). Four studies (n = 12; 33%) reported a positive significant effect on either length of stay or time to revisit, and one study reported a negative effect (n = 12; 6%). All studies investigating mortality (n = 6), patient‐reported outcome (n = 7) and cost‐effectiveness (n = 1) showed no significant results. This MiniReview indicates that multifaceted pharmacist‐led interventions in a hospital setting may improve the quality of medication use and reduce hospital visits and length of stay, while no effect was seen on mortality, patient‐reported outcome and cost‐effectiveness.     

Global Research Trends in Lithium Toxicity from 1913 to 2015: A Bibliometric Analysis

Lithium salts have been used to treat psychiatric disorders since the 1940s and are currently used in prophylaxis and treatment of depression and bipolar disorder. Therefore, we conducted this study to assess lithium toxicity‐related publications using bibliometric approaches from a health point of view to assess global research trends in the lithium toxicity field to offer guidance to future research in this field. The data were retrieved from the online version of Scopus database on 6 August 2016. All records with the term ‘lithium’ in the title were retrieved, and those related to lithium toxicity were evaluated. There were a total of 1241 publications related to lithium toxicity published from 1913 to 2016. Articles (971 or 78.2%) were the most common type, followed by letters (179 or 14.4%) and reviews (61 or 4.9%). The annual publication of articles increased slightly after 1950 and the total number of publications related to lithium toxicity fluctuated with three peaks occurred in 1978, 1985 and 2014. The USA was the predominant country (25.38%), followed by the UK (7.82%), France (6.85%) and Canada (3.55%). Denmark had the highest productivity of publication after standardization by gross domestic product and population size. The average number of citations per article was 9.24, and the h‐index for all publications in the field of lithium toxicity was 46. The highest h‐index value was achieved by the USA (31) followed by the UK (21) and Canada (13). The Lancet was the highest ranked journal with 27 articles, followed by American Journal of Psychiatry with 23 articles. This study provides a bibliometric analysis on the global research trends in lithium toxicity studies during 1913–2015. There has been a progressive increase in the number of publications related to lithium toxicity published in the last decade, and most of the studies related to lithium toxicity arose from the USA and the UK.     

Improving linkage with substance abuse treatment using brief case management and motivational interviewing

BACKGROUND: Poor linkage with substance abuse treatment remains a problem, negating the benefits that can accrue to both substance abusers and the larger society. Numerous behavioral interventions have been tested to determine their potential role in improving linkage. METHODS: A randomized clinical trial of 678 substance abusers compared the linkage effect of two brief interventions with the referral standard of care (SOC) at a centralized intake unit (CIU). Interventions included five sessions of strengths-based case management (SBCM) or one session of motivational interviewing (MI). A priori hypotheses predicted that both interventions would be better than the standard of care in predicting linkage and that SBCM would be more effective than MI. We analyzed the effect of the two interventions on overall treatment linkage rates and by treatment modality. Logistic regression analysis examined predictors of treatment linkage for the sample and each group. RESULTS: Two hypotheses were confirmed in that SBCM (n=222) was effective in improving linkage compared to the SOC (n=230), 55.0% vs. 38.7% (p<.01). SBCM improved linkage more than MI (55.0% vs. 44.7%, p<.05). Motivational interviewing (n=226) was not significantly more effective in improving linkage than the standard of care (44.7% vs. 38.7%; p>.05). The three trial groups differed only slightly on the client characteristics that predicted linkage with treatment. CONCLUSIONS: The results of this study confirm a body of literature that supports the effectiveness of case management in improving linkage with treatment. The role of motivational interviewing in improving linkage was not supported. Results are discussed in the context of other case management and motivational interviewing linkage studies.     

QT prolongation and Torsades de Pointes in patients previously treated with anthracyclines

Anthracyclines reduce myocardial repolarization reserve and might increase the risk for Torsades de Pointes a long time after treatment. We studied all the publications concerning Torsades de Pointes in patients previously treated with anthracyclines to investigate the clinical circumstances leading to this rare life-threatening complication. Our literature search yielded nine reports of 11 patients who had developed Torsades de Pointes anywhere from weeks to years following treatment with anthracyclines. One of the patients was hospitalized in our medical center. Risk factors and triggers for Torsades de Pointes, among other clinical aspects, were analyzed in each report. Most patients (n=10; 90.9%) were previously treated with anthracyclines owing to acute leukemias: acute myelogenous leukemia (n=5), acute lymphocytic leukemia (n=3) and acute promyelocytic leukemia (n=2). One patient was previously treated with anthracyclines owing to Hodgkin's lymphoma. Most patients were women (n=9; 81.8%). The most prevalent triggers for Torsades de Pointes were the administration of a QT-prolonging agent (n=10; 90.9%) and hypokalemia (n=9; 81.8%). Azole derivatives were the most prevalent of the QT-prolonging agents that triggered Torsades de Pointes (n=5; 45.5%). Although four patients suffered from anthracycline-induced left ventricular dysfunction and five other patients had only one or two questionable triggers for Torsades de Pointes, in only two of these cases the authors considered previous treatment with anthracyclines as a risk factor for Torsades de Pointes. Previous treatment with anthracycline is an underestimated risk factor for Torsades de Pointes. Possible triggers includes azole derivatives, other QT-prolonging agents and hypokalemia. Women patients are particularly at risk.     

Early antibiotic treatment of pseudomonas aeruginosa colonisation in cystic fibrosis: a critical review of the literature

Aim To assess the evidence supporting early antibiotic treatment in asymptomatic cystic fibrosis (CF) patients colonised by Pseudomonas aeruginosa (PA).Methods We carried out a computerised (Medline, Embase) and hand search of journals for suitable publications. All English-language clinical studies regarding the efficacy of early antibiotic treatment on PA colonisation in asymptomatic patients were considered. Each eligible publications fitting these criteria were assessed for the following outcome measures: frequency of positive PA cultures; serum level of precipitating antibodies; lung function; survival; number of hospitalisations; adverse effects and resistance to antibiotics.Results Of the 11 studies eventually considered, 3 were randomised—2 versus placebo— and 8 were cohort studies—2 of which had historical controls. Overall, 309 patients (population range 7–91 patients) were recruited. There was a high variability between the individual studies for age, outcome measures, duration of follow-up (1 to 44 months) and treatment (three studies used only aerosol tobramycin, one colistin, four aerosol colistin plus oral ciprofloxacin, one used intravenous treatment and two miscellaneous therapy). An overall evaluation indicated that early antibiotic treatment can reduce the number of positive cultures and the anti-PA antibody titre. In one study, FEV1 was better in the treated group (oral ciprofloxacin and nebulised colistin) than in historical controls, while in one placebo-controlled trial, no effect on lung function was shown after 1 year of tobramycin inhalation. Collateral effects and bacterial resistance were not increased. The short follow-up did not allow definite conclusions with regard to the long-term progression of respiratory insufficiency or survival.Conclusions Evidence was found that antibiotic treatment can reduce the rate of positive cultures and of anti-PA antibody titres in asymptomatic CF patients with newly isolated PA. Different therapeutic options have not been directly compared: a multi-centre comparative study needs to be carried out.     

Effect of the Na+-channel modulator BDF 9148 on Ca2+-sensitivity and force of contraction of hypertrophic myocardium from transgene rats harboring the mouse Renin gene (TG(mREN2)27)

The present study aimed to investigate the inotropic effect of the Na⁺-channel modulator BDF 9148 in hypertrophic myocardium compared to control tissue. Thus, TG(mREN2)27 rats (TGR), a model with hypertension induced cardiac hypertrophy, was compared with age matched Sprague-Dawley rats (SPDR). The effect of BDF 9148 (0.01–10 μM) on force of contraction (1 Hz, 37°C), the force-frequency relationship (0.5–7 Hz) and the frequency-dependent diastolic tension (0.5–7 Hz) was studied on leftventricular papillary muscles from SPDR and TGR. Chemically skinned muscle fibers of the same hearts were used to examine the influence of BDF 9148 on the Ca²⁺-sensitivity of the contractile proteins. For control the Ca²⁺-sensitizer EMD 57033 was examined. In addition the Na⁺/K⁺-ATPase activity was measured in both, SPDR and TGR. BDF 9148 showed a concentration dependent positive inotropic effect in SPDR and TGR cardiac preparations. Comparing SPDR and TGR, a higher effectiveness of BDF 9148 on TGR was found, while the potency was unchanged. With increasing stimulation rates a significant higher decrease in force of contraction in TGR compared to SPDR was observed. In addition, a significant higher increase in diastolic tension was found in TGR. After exposure to 1 μM BDF 9148 the decrease in force of contraction was significantly reduced in both SPDR and TGR, while only in TGR the increase in diastolic tension was reduced. BDF 9148 had no effect on the Ca²⁺-sensitivity or maximal developed tension of skinned fiber preparations from SPDR or TGR. In contrast, the Ca²⁺-sensitizer EMD 57033 increased the Ca²⁺-sensitivity. The activity of the Na⁺/K⁺-ATPase was significantly reduced in TGR compared to controls. Conclusions: The Na⁺-channel modulator BDF 9148 was more effective in hypertrophic compared to control myocardium in increasing force of contraction, enhancing frequency-dependent force generation and reducing diastolic tension. These effects were not mediated via interaction with the contractile apparatus. The enhanced effectiveness of Na⁺-channel modulation in hypertrophic myocardium could result from alterations of the Na⁺ homeostasis, i. e. a reduced Na⁺/K⁺-ATPase activity. Received: 13 August 1997 / Accepted: 4 February 1998     

l‐arginine and l‐NMMA for assessing cerebral endothelial dysfunction in ischaemic cerebrovascular disease: A systematic review

Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l ‐arginine and N^G‐monomethyl‐l ‐arginine (l ‐NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l ‐arginine or l ‐NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible according to inclusion and exclusion criteria. Studies investigated the effect of age (n=2), type 2 diabetes mellitus (DM) (n=1), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (n=1), leukoaraiosis (n=1), and prior ischaemic stroke or transient ischaemic attack (TIA) (n=2) on cerebral ED. Most studies applied transcranial Doppler to quantify cerebral ED. Endothelium‐dependent vasodilatation (EDV) induced by l ‐arginine was impaired in elderly and subjects with leukoaraiosis, but enhanced in CADASIL patients. Studies including subjects with prior ischaemic stroke or TIA reported both enhanced and impaired EDV to l ‐arginine. Responses to l ‐NMMA deviated between subjects with type 2 DM and the elderly. We found only few studies investigating cerebral endothelial responses to l ‐arginine and l ‐NMMA in subjects with vascular risk factors or ischaemic cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease.     

Effectiveness and cost effectiveness of pharmacist input at the ward level: a systematic review and meta-analysis

BackgroundPharmacists play important role in ensuring timely care delivery at the ward level. The optimal level of pharmacist input, however, is not clearly defined.ObjectiveTo systematically review the evidence that assessed the outcomes of ward pharmacist input for people admitted with acute or emergent illness.MethodsThe protocol and search strategies were developed with input from clinicians. Medline, EMBASE, Centre for Reviews and Dissemination, The Cochrane Library, NHS Economic Evaluations, Health Technology Assessment and Health Economic Evaluations databases were searched.Inclusion criteria specified the population as adults and young people (age >16 years) who are admitted to hospital with suspected or confirmed acute or emergent illness. Only randomised controlled trials (RCTs) published in English were eligible for inclusion in the effectiveness review. Economic studies were limited to full economic evaluations and comparative cost analysis. Included studies were quality-assessed. Data were extracted, summarised. and meta-analysed, where appropriate.ResultsEighteen RCTs and 7 economic studies were included. The RCTs were from USA (n = 3), Sweden (n = 2), Belgium (n = 2), China (n = 2), Australia (n = 2), Denmark (n = 2), Northern Ireland, Norway, Canada, UK and Netherlands. The economic studies were from UK (n = 2), Sweden (n = 2), Belgium and Netherlands. The results showed that regular pharmacist input was most cost effective. It reduced length-of-stay (mean = −1.74 days [95% CI: 2.76, −0.72], and increased patient and/or carer satisfaction (Relative Risk (RR) = 1.49 [1.09, 2.03] at discharge). At £20,000 per quality-adjusted life-year (QALY)-gained cost-effectiveness threshold, it was either cost-saving or cost-effective (Incremental Cost Effectiveness Ratio (ICER) = £632/QALY-gained). No evidence was found for 7-day pharmacist presence.ConclusionsPharmacist inclusion in the ward multidisciplinary team improves patient safety and satisfaction and is cost-effective when regularly provided throughout the ward stay. Research is needed to determine whether the provision of 7-day service is cost-effective.     

Global Trends in Aspirin Resistance‐Related Research from 1990 to 2015: A Bibliometric Analysis

Aspirin resistance can be defined as the inability of the usual dose of aspirin medication to produce its antithrombotic effect. Patients with diabetes or cardiovascular disease are at higher risk of stroke, myocardial infarction or cardiovascular death due to aspirin resistance. The aim of this bibliometric study was to identify and analyse the status and trends of aspirin resistance research production at global level through publications indexed in the Scopus database; this will shed new light on future research trends and help researchers predict dynamic direction of research. Literature search using the Scopus database was conducted to assess publications related to aspirin resistance. The selected publications included the terms related to aspirin resistance in the title, abstract or keywords. The searching was accomplished on 20 March 2016 and can be considered to include all publications up to 31 December 2015. Global cumulative publication output on aspirin resistance consists of 986 papers during 1990–2015. Among the 986 documents, 19 (1.9%) were published before 2000, 567 (57.5%) were published from 2000 to 2009 and 400 (40.6%) were published from 2010 to 2015, with peak of publications on this topic in 2008. The leading country in the field of aspirin resistance was the United States, which had the greatest counts of independent articles (165) and international collaboration articles (44). Turkey was in the second rank with 78 articles, followed by Italy (68), the UK (62) and Poland (60). The total number of citations for all documents was 26,342, and the average citations per document were 26.7. The h‐index for all aspirin resistance publications was 82. This study presents the results of the first bibliometric study (including quantitative and qualitative analysis) of scientific publications in the field of aspirin renitence at global level. Aspirin resistance‐related researches have notably increased in the last years, especially from 2000 to 2015. The United States is the most prolific country, not only in research quantity but also in quality. Furthermore, Turkey and European countries provided more research related to aspirin resistance than other regions such as the developing countries.     

Meta-analysis: role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users

Aim : To evaluate whether eradication of Helicobacter pylori prevents peptic ulcer in non‐steroidal anti‐inflammatory drug users by means of a meta‐analysis. Material and methods : A systematic search was performed in MEDLINE, EMBASE, the Cochrane Controlled Trials Register and the AGA congress. Randomized trials comparing H. pylori eradication vs. non‐eradication or eradication vs. a proton pump inhibitor in patients receiving a non‐steroidal anti‐inflammatory drug were selected. Results : Five studies and 939 patients were included in the analysis; 34 of 459 (7.4%) patients developed a peptic ulcer in the eradicated group vs. 64 of 480 (13.3%) in the control group. The odds ratio was 0.43 (95% confidence interval: 0.20–0.93). Sub‐analyses showed a significant reduction of risk for non‐steroidal anti‐inflammatory drug‐naive (odds ratio = 0.26; 95% confidence interval: 0.14–0.49) but not for previously treated patients (odds ratio = 0.95, 95% confidence interval: 0.53–1.72). Two studies with a total of 385 patients compared eradication vs. a proton pump inhibitor; five of 196 (2.6%) developed a peptic ulcer in the eradicated group vs. zero of 189 (0%) in the proton pump inhibitor group (odds ratio = 7.43; 95% confidence interval: 1.27–43.6). Conclusion : Helicobacter pylori eradication reduces the incidence of peptic ulcer in the overall population receiving non‐steroidal anti‐inflammatory drugs. It appears to be especially effective when performed in non‐steroidal anti‐inflammatory drug‐naïve patients. Nonetheless, eradication seems less effective than treatment with a maintenance proton pump inhibitor for preventing non‐steroidal anti‐inflammatory drug‐associated ulcers.     

Serial pharmacological prescribing practices for tic management in Tourette syndrome

Pharmacological treatments for Tourette syndrome (TS) vary in efficacy between different patients. The evidence base is limited as even high quality controlled studies tend to be of relatively short duration which may lose relevance in clinical usage. Patients are frequently treated with serial agents in the search for efficacy and tolerability. The success of this strategy has not been previously documented. We examined 400 consecutive TS patients seen over a 10‐year period, some with a longer prior history in other clinics; 255/400 (64%) were prescribed medication. We present this heterogeneous cohort in terms of the number of drugs they had tried, and as a proxy measure of some benefit of the last drug used, whether it had been prescribed under our supervision for ≥5 months. The most commonly prescribed medications were aripiprazole (64%), clonidine (40%), risperidone (30%) and sulpiride (29%) with changes in prescribing practises over the period examined. The number of different drugs tried were one (n = 155), two (n = 69), three (n = 36), four (n = 14), five (n = 15), six (n = 5), seven (n = 2) and eight (n = 1). The data illustrate the difficulty in drug treatment of tics and suggest that even after trials of several agents there is potential benefit in trying further options. Copyright © 2015 John Wiley & Sons, Ltd.     

Do antipsychotics increase diabetes risk in children and adolescents?

Introduction: Glucose dysregulation and type 2 diabetes mellitus (T2DM) are feared antipsychotic drug adverse effects. Despite increasing utilization, data about antipsychotic risk of T2DM in youth are scarce.

Areas covered: We conducted a systematic PubMed/MEDLINE search until 15 May 2014 focusing on studies with ≥ 20 youths aged ≤ 24 years, reporting quantitative data on: i) change in fasting glucose, hemoglobin A1c, insulin or insulin resistance after antipsychotic initiation (studies = 19, n = 2123,age = 13.3 years, follow up = 28.8 weeks); or ii) prevalence (studies = 4) or incidence (studies = 8, follow up = 1.57 years) of T2DM in antipsychotic-exposed youth (studies = 10, n = 65,486, age = 14.2 years) versus healthy controls (studies = 4, n = 246,828), psychiatric controls (studies = 5, n = 61,784) or without control groups (studies = 2).

Expert opinion: Antipsychotics are associated with early adverse changes in glucose metabolism that are greater with all analyzable antipsychotics compared to controls, being highest with olanzapine, followed by quetiapine, aripiprazole and risperidone; but data were scarce. Although T2DM is fortunately rare in antipsychotic-treated youth, its prevalence (odds ratio [OR] = 8.176, 95% CI = 7.139 – 9.362) and incidence (OR = 1.450, 95% CI = 1.101 – 1.911, p = 0.006) were higher than in healthy controls. Similarly, T2DM prevalence (OR = 3.475, 95% CI = 3.019 – 4.001, p < 0.0001) and incidence (OR = 5.376, 95% CI = 4.004 – 7.233, p < 0.0001, excluding one outlying study) were higher than in psychiatric controls. Antipsychotics should only be used after lower-risk interventions failed, and inappropriately low clinical metabolic monitoring must be remedied.     

Meta-analysis: the diagnostic accuracy of lactose breath hydrogen or lactose tolerance tests for predicting the North European lactase polymorphism C/T-13910

Aliment Pharmacol Ther 2012; 35: 429–440

Summary

Background The diagnostic accuracy of two indirect tests of lactose digestion, lactose breath hydrogen and lactose tolerance tests, have not been systematically reviewed for comparison with available publications on genotype. Aim To perform a meta‐analysis of available studies that compares the north‐European genetic polymorphism C/T‐13910 with the lactose breath hydrogen and the lactose tolerance tests, to determine their ability to predict geno/phenotype relationships. We examine the effects of lactose loading dose, inclusion of children and latitudes of study centre on comparative outcome. Methods An electronic database of the literature as well as individual references in articles were searched with the theme of genetics of lactase and comparisons with breath or lactose tolerance tests were carried out. Random effect and fixed effect models were used for breath and lactose tolerance tests respectively, to report summary accuracy measures with 95% confidence intervals (CI). Results The search revealed 19 studies: 17 evaluated breath hydrogen, five lactose tolerance test (3/17 overlapped). Overall sensitivity was 0.88 (CI, 0.85–0.90), specificity was 0.85 (CI, 0.82–0.87) for breath test. Heterogeneity was explored by adjusting for studies including children, high or low dose lactose and to some extent by site of study. The lactose tolerance test showed sensitivity of 0.94 (0.9–0.97) and specificity of 0.90 (0.84–0.95) with a nonsignificant heterogeneity. Conclusion The diagnostic accuracy of both tests individually reflects expected geno/phenotypes when the populations are well defined.     

Predictors of publication productivity among hospital pharmacists in France and Quebec

Objective

To describe publications by hospital pharmacists in France and Quebec and evaluate factors predictive of publication productivity.

Method

Variables related to scientific publication productivity were identified through a search of the literature and organized into 4 themes (ie, personal and professional characteristics, hospital activities, research and publishing activities, publication-related motivations and perceptions). A questionnaire was developed that included short-answer items and 58 multiple-choice questions to determine respondents'' level of agreement with statements about their motivations and perceptions surrounding publishing.

Results

Four hundred twenty-two hospital pharmacists (218 respondents from France and 204 from Quebec) were recruited. Respondents from France were more prolific than those from Quebec, even when considering factors such as time worked and gender. Furthermore, the percentage of respondents working in a university health center was lower in France than Quebec (46% vs. 70%, p = 0.001), as was the percentage of respondents indicating a mastery of English (43% vs. 88%, p = 0.001).

Conclusion

Seven factors were predictive of the number of publications per respondent in France and Quebec: practicing hospital pharmacy in France, being male, having academic duties or a PhD, having participated in a clinical trial, having secured funding in one''s own name for a research project, and allocating a greater number of hours per week to research.     

Application of Bayes theorem to aminoglycoside-associated nephrotoxicity: comparison of extended-interval dosing, individualized pharmacokinetic monitoring, and multiple-daily dosing

The objective of this study was to examine the incidence of aminoglycoside-associated nephrotoxicity related to extended-interval dosing, individualized pharmacokinetic monitoring, and multiple-daily dosing by applying Bayes theorem. An electronic literature search of MEDLINE (1966-2003) and a manual search of references from published meta-analyses and review articles were performed. Studies using extended-interval dosing, individualized pharmacokinetic monitoring, or multiple-daily dosing and reported aminoglycoside-associated nephrotoxicity for patients > or = 16 years of age were included. Quality scores were assigned based on the rigor of definition of aminoglycoside-associated nephrotoxicity, duration of therapy, and length of follow-up of renal function after completion of therapy. Inclusion criteria were then based on these quality scores. Quantitative data on the incidence of aminoglycoside-associated nephrotoxicity were abstracted. Twelve extended-interval dosing studies (n = 916), 10 individualized pharmacokinetic monitoring studies (n = 2066), and 27 multiple-daily dosing studies (n = 4251) met the inclusion criteria. Prior probabilities of aminoglycoside-associated nephrotoxicity were derived from a combination of a review of published studies and expert judgment. The maximum densities for the final posterior probabilities of aminoglycoside-associated nephrotoxicity for extended-interval dosing, individualized pharmacokinetic monitoring, and multiple-daily dosing were located at 12% to 13%, 10% to 11%, and 13% to 14%, respectively. Application of Bayes theorem demonstrates that aminoglycoside dosing by individualized pharmacokinetic monitoring results in less aminoglycoside-associated nephrotoxicity than extended-interval dosing or multiple-daily dosing.     

Letter from the Editor

Antibacterials are frequently associated with idiosyncratic drug‐induced liver injury (DILI). The objective of this study was to estimate the risk of macrolides and amoxicillin/clavulanate (AMC) on DILI. We conducted a systematic review (SR) and meta‐analysis (MA) with studies retrieved from PubMed, Cochrane Library Plus, Web of Knowledge, clinicaltrials.gov, Livertox and Toxline (1980–2014). We searched for macrolides, AMC and MeSH and synonym terms for DILI. We included all study designs except case reports/series, all population ages and studies with a placebo/non‐user comparator. We summarized the evidence with a random‐effects MA. Quality of the studies was appraised with a checklist developed for SR of adverse effects. Heterogeneity and publication bias were assessed with different exploratory tools. We finally included 10 (two randomized clinical trials, six case–control, one cohort and one case–population studies) and 9 (case–population excluded) articles in the SR and MA, respectively. The overall summary relative risk of DILI for macrolides was 2.85 [95% confidence interval (CI) 1.81–4.47], p < 0.0001, I² = 57%. Three studies were perceived to be missing in the area of low statistical significance. Year of study and selected exposure window partly explained the variability between studies. For AMC, the risk of DILI was 9.38 (95% CI 0.65–135.41) p = 0.3, I2 = 95%. In conclusion, although spontaneous reports and case series have long established an association between macrolides and AMC with acute liver injury, these SR and MA have assessed the magnitude of this association. The low incidence of DILI and the therapeutic place of these antibiotics might tilt the balance in favour of their benefits.     

Alcohol use disorders in EU countries and Norway: an overview of the epidemiology.

Based on a systematic literature search and an expert survey, publications after 1990 on prevalence of alcohol use disorders (AUD) in EU countries and Norway were reviewed. The search was restricted to studies using the DSM-IIIR or DSM-IV, or ICD-10, plus validated instruments to assess AUD. Using only representative general population surveys, the weighted median estimates for 12-month prevalence rates for dependence alone are 6.1% for males (arithmetic mean 5.0%; interquartile range 0.4% to 7.5%) and 1.1% for females (arithmetic mean 1.4%; interquartile range 0.1% to 2.1%). Results thus showed, that AUD constitute a high burden of disease in Europe, but there was high variability of prevalence. Men have higher prevalence rates of AUD than women. No clear pictures emerged with respect to age and AUD prevalence, or with respect to urban vs. rural and AUD prevalence. The discussion highlights potential explanations for the high variability of prevalence between countries, and the fact, that AUD constitute only a small part of all alcohol-related harm.     

The impact of influenza on working days lost: a review of the literature

Seasonal influenza is a prevalent and highly contagious acute respiratory disease that, year on year, results in increased morbidity and mortality on a global scale. Because of the widespread and debilitating nature of the disease, annual influenza epidemics result in substantial workplace absenteeism, and the associated cost of lost productivity is a significant component of the substantial financial burden of the disease to society. The objective of this review was to identify studies that had attempted to quantify the impact of influenza upon otherwise healthy adults in terms of working days lost associated with an episode of influenza.Studies were included if they reported estimates of working days lost due to clinical, physician and/or self-diagnosis in adult patients or their dependants, or where this figure could be estimated from the data. Searches were conducted in MEDLINE, EMBASE, BIOSIS and the Cochrane Collaboration for articles published since 1995 in English, French or German. Of the 289 papers identified in the search, 28 (9.7%) met the inclusion criteria. The studies, involving study sites in North America, Western Europe, Asia and Australia, were categorized into three groups: (i) those reporting influenza diagnoses confirmed by laboratory testing, i.e. studies where influenza was the unambiguous cause of the working days lost (n = 7 studies reported in ten publications); (ii) those where influenza was confirmed by a physician without an accompanying laboratory test (n = 4 studies); and (iii) those where influenza was self-reported by study participants (n = 14 studies). Qualitative reporting of results was performed because of the large degree of heterogeneity observed between studies, potentially complicating the interpretation of any meta-analysis.The results from studies involving a laboratory-confirmed influenza diagnosis suggested that the mean number of working days lost ranged between 1.5 and 4.9 days per episode. Those papers that detailed working days lost per episode following physician diagnosis of influenza reported a range of 3.7-5.9 days per episode. Finally, estimates from papers reporting working days lost per episode of self-reported influenza ranged from <1 day to 4.3 days per episode.Influenza imposes a significant burden on society, and this review highlights the significant economic impact it causes, i.e. the loss of productivity caused by both absenteeism and by staff functioning at reduced capacity even after they have returned to work. A number of prophylaxis and treatment options exist for influenza and should be given serious consideration in an attempt to reduce the economic burden on society.