Differences in the Volume of Pharmaceutical Advertisements between Print General Medical Journals

Background

Pharmaceutical advertisements have been argued to provide revenue that medical journals require but they are intended to alter prescribing behaviour and they are known to include low quality information. We determined whether a difference exists in the current level of pharmaceutical advertising in print general medical journals, and we estimated the revenue generated from print pharmaceutical advertising.

Methods

Six print general medical journals in Canada, the United States, and the United Kingdom were sampled between 2007 and 2012. The number of advertisements and other journal content in selected issues of the Canadian Medical Association Journal (CMAJ), Canadian Family Physician (CFP), Journal of the American Medical Association (JAMA), New England Journal of Medicine (NEJM), British Medical Journal (BMJ), and Lancet were determined. Revenue gained from pharmaceutical advertising was estimated using each journal''s 2013 advertising price list.

Findings

The two Canadian journals sampled (CMAJ, CFP) contained five times more advertisements than the two American journals (JAMA, NEJM), and two British journals (BMJ, Lancet) (p<0.0001). The estimated annual revenue from pharmaceutical advertisements ranged from £0.025 million (for Lancet) to £3.8 million (for JAMA). The cost savings due to revenue from pharmaceutical advertising to each individual subscriber ranged from £0.02 (for Lancet) to £3.56 (for CFP) per issue.

Conclusion

The volume of pharmaceutical advertisements differs between general medical journals, with the two Canadian journals sampled containing the most advertisements. International and temporal variations suggest that there is an opportunity for all general medical journals to reduce the number of pharmaceutical advertisements, explore other sources of revenue, and increase transparency regarding sources of revenue.     

Quality Assessment of TPB-Based Questionnaires: A Systematic Review

Objective

This review is aimed at assessing the quality of questionnaires and their development process based on the theory of planned behavior (TPB) change model.

Methods

A systematic literature search for studies with the primary aim of TPB-based questionnaire development was conducted in relevant databases between 2002 and 2012 using selected search terms. Ten of 1,034 screened abstracts met the inclusion criteria and were assessed for methodological quality using two different appraisal tools: one for the overall methodological quality of each study and the other developed for the appraisal of the questionnaire content and development process. Both appraisal tools consisted of items regarding the likelihood of bias in each study and were eventually combined to give the overall quality score for each included study.

Results

8 of the 10 included studies showed low risk of bias in the overall quality assessment of each study, while 9 of the studies were of high quality based on the quality appraisal of questionnaire content and development process.

Conclusion

Quality appraisal of the questionnaires in the 10 reviewed studies was successfully conducted, highlighting the top problem areas (including: sample size estimation; inclusion of direct and indirect measures; and inclusion of questions on demographics) in the development of TPB-based questionnaires and the need for researchers to provide a more detailed account of their development process.     

Quality Indicators for Safe Medication Preparation and Administration: A Systematic Review

Background

One-third of all medication errors causing harm to hospitalized patients occur in the medication preparation and administration phase, which is predominantly a nursing activity. To monitor, evaluate and improve the quality and safety of this process, evidence-based quality indicators can be used.

Objectives

The aim of study was to identify evidence-based quality indicators (structure, process and outcome) for safe in-hospital medication preparation and administration.

Methods

MEDLINE, EMBASE and CINAHL were searched for relevant studies published up to January 2015. Additionally, nine databases were searched to identify relevant grey literature. Two reviewers independently selected studies if (1) the method for quality indicator development combined a literature search with expert panel opinion, (2) the study contained quality indicators on medication safety, and (3) any of the quality indicators were applicable to hospital medication preparation and administration. A multidisciplinary team appraised the studies independently using the AIRE instrument, which contains four domains and 20 items. Quality indicators applicable to in-hospital medication preparation and administration were extracted using a structured form.

Results

The search identified 1683 studies, of which 64 were reviewed in detail and five met the inclusion criteria. Overall, according to the AIRE domains, all studies were clear on purpose; most of them applied stakeholder involvement and used evidence reasonably; usage of the indicator in practice was scarcely described. A total of 21 quality indicators were identified: 5 structure indicators (e.g. safety management and high alert medication), 11 process indicators (e.g. verification and protocols) and 5 outcome indicators (e.g. harm and death). These quality indicators partially cover the 7 rights.

Conclusion

Despite the relatively small number of included studies, the identified quality indicators can serve as an excellent starting point for further development of nursing specific quality indicators for medication safety. Especially on the right patient, right route, right time and right documentation there is room future development of quality indicators.     

An Assessment of the Methodological Quality of Published Network Meta-Analyses: A Systematic Review

ObjectiveTo assess the methodological quality of published network meta-analysis.DesignSystematic review.MethodsWe searched the medical literature for network meta-analyses of pharmaceuticals. We assessed general study characteristics, study transparency and reproducibility, methodological approach, and reporting of findings. We compared studies published in journals with lower impact factors with those published in journals with higher impact factors, studies published prior to January 1^st, 2013 with those published after that date, and studies supported financially by industry with those supported by non-profit institutions or that received no support.ResultsThe systematic literature search identified 854 citations. Three hundred and eighteen studies met our inclusion criteria. The number of network meta-analyses has grown rapidly, with 48% of studies published since January 2013. The majority of network meta-analyses were supported by a non-profit institution or received no support (68%). We found considerable inconsistencies among reviewed studies. Eighty percent reported search terms, 61% a network diagram, 65% sufficient data to replicate the analysis, and 90% the characteristics of included trials. Seventy percent performed a risk of bias assessment of included trials, 40% an assessment of model fit, and 56% a sensitivity analysis. Among studies with a closed loop, 69% examined the consistency of direct and indirect evidence. Sixty-four percent of studies presented the full matrix of head-to-head treatment comparisons. For Bayesian studies, 41% reported the probability that each treatment was best, 31% reported treatment ranking, and 16% included the model code or referenced publicly-available code. Network meta-analyses published in higher impact factors journals and those that did not receive industry support performed better across the assessment criteria. We found few differences between older and newer studies.ConclusionsThere is substantial variation in the network meta-analysis literature. Consensus among guidelines is needed improve the methodological quality, transparency, and consistency of study conduct and reporting.     

A Systematic Review of High Quality Diagnostic Tests for Chagas Disease

Background

There is significant heterogeneity in reported sensitivities and specificities of diagnostic serological assays for Chagas disease, as might be expected from studies that vary widely according to setting, research design, antigens employed, and reference standard. The purpose of this study is to summarize the reported accuracy of serological assays and to identify sources of heterogeneity including quality of research design. To avoid associated spectrum bias, our analysis was limited to cohort studies.

Methods

We completed a search of PubMed, a bibliographic review of potentially relevant articles, and a review of articles identified by a study author involved in this area of research. Studies were limited to prospective cohort studies of adults published since 1985. Measures of diagnostic accuracy were pooled using a Der Simonian Laird Random Effects Model. A subgroup analysis and meta regression were employed to identify sources of heterogeneity. The QUADAS tool was used to assess quality of included studies and Begg''s funnel plot was used to assess publication bias.

Results

Eighteen studies and 61 assays were included in the final analysis. Significant heterogeneity was found in all pre-determined subgroups. Overall sensitivity was 90% (95% CI: 89%–91%) and overall specificity was 98% (95% CI: 98%–98%).

Conclusion

Sensitivity and specificity of serological assays for the diagnosis of Chagas disease appear less accurate than previously thought. Suggestions to improve the accuracy of reporting include the enrollment of patients in a prospective manner, double blinding, and providing an explicit method of addressing subjects that have an indeterminate diagnosis by either the reference standard or index test.     

Dissemination Bias in Systematic Reviews of Animal Research: A Systematic Review

Background

Systematic reviews of preclinical studies, in vivo animal experiments in particular, can influence clinical research and thus even clinical care. Dissemination bias, selective dissemination of positive or significant results, is one of the major threats to validity in systematic reviews also in the realm of animal studies. We conducted a systematic review to determine the number of published systematic reviews of animal studies until present, to investigate their methodological features especially with respect to assessment of dissemination bias, and to investigate the citation of preclinical systematic reviews on clinical research.

Methods

Eligible studies for this systematic review constitute systematic reviews that summarize in vivo animal experiments whose results could be interpreted as applicable to clinical care. We systematically searched Ovid Medline, Embase, ToxNet, and ScienceDirect from 1^st January 2009 to 9^th January 2013 for eligible systematic reviews without language restrictions. Furthermore we included articles from two previous systematic reviews by Peters et al. and Korevaar et al.

Results

The literature search and screening process resulted in 512 included full text articles. We found an increasing number of published preclinical systematic reviews over time. The methodological quality of preclinical systematic reviews was low. The majority of preclinical systematic reviews did not assess methodological quality of the included studies (71%), nor did they assess heterogeneity (81%) or dissemination bias (87%). Statistics quantifying the importance of clinical research citing systematic reviews of animal studies showed that clinical studies referred to the preclinical research mainly to justify their study or a future study (76%).

Discussion

Preclinical systematic reviews may have an influence on clinical research but their methodological quality frequently remains low. Therefore, systematic reviews of animal research should be critically appraised before translating them to a clinical context.     

Toxocariasis in North America: A Systematic Review

Toxocariasis is an important neglected tropical disease that can manifest as visceral or ocular larva migrans, or covert toxocariasis. All three forms pose a public health problem and cause significant morbidity in areas of high prevalence. To determine the burden of toxocariasis in North America, we conducted a systematic review of the literature following PRISMA guidelines. We found 18 articles with original prevalence, incidence, or case data for toxocariasis. Prevalence estimates ranged from 0.6% in a Canadian Inuit community to 30.8% in Mexican children with asthma. Commonly cited risk factors included: African-American race, poverty, male sex, and pet ownership or environmental contamination by animal feces. Increased prevalence of Toxocara spp. infection was linked in a group of case control studies conducted in Mexico to several high risk groups including waste pickers, asthmatic children, and inpatient psychiatry patients. Further research is needed to determine the true current burden of toxocariasis in North America; however the prevalence estimates gathered in this review suggest that the burden of disease is significant.     

Case-Only Designs in Pharmacoepidemiology: A Systematic Review

Background

Case-only designs have been used since late 1980’s. In these, as opposed to case-control or cohort studies for instance, only cases are required and are self-controlled, eliminating selection biases and confounding related to control subjects, and time-invariant characteristics. The objectives of this systematic review were to analyze how the two main case-only designs – case-crossover (CC) and self-controlled case series (SCCS) – have been applied and reported in pharmacoepidemiology literature, in terms of applicability assumptions and specificities of these designs.

Methodology/Principal Findings

We systematically selected all reports in this field involving case-only designs from MEDLINE and EMBASE up to September 15, 2010. Data were extracted using a standardized form. The analysis included 93 reports 50 (54%) of CC and 45 (48%) SCCS, 2 reports combined both designs. In 12 (24%) CC and 18 (40%) SCCS articles, all applicable validity assumptions of the designs were fulfilled, respectively. Fifty (54%) articles (15 CC (30%) and 35 (78%) SCCS) adequately addressed the specificities of the case-only analyses in the way they reported results.

Conclusions/Significance

Our systematic review underlines that implementation of CC and SCCS designs needs to be more rigorous with regard to validity assumptions, as well as improvement in results reporting.     

Medical Student Research: An Integrated Mixed-Methods Systematic Review and Meta-Analysis

Importance

Despite the rapidly declining number of physician-investigators, there is no consistent structure within medical education so far for involving medical students in research.

Objective

To conduct an integrated mixed-methods systematic review and meta-analysis of published studies about medical students'' participation in research, and to evaluate the evidence in order to guide policy decision-making regarding this issue.

Evidence Review

We followed the PRISMA statement guidelines during the preparation of this review and meta-analysis. We searched various databases as well as the bibliographies of the included studies between March 2012 and September 2013. We identified all relevant quantitative and qualitative studies assessing the effect of medical student participation in research, without restrictions regarding study design or publication date. Prespecified outcome-specific quality criteria were used to judge the admission of each quantitative outcome into the meta-analysis. Initial screening of titles and abstracts resulted in the retrieval of 256 articles for full-text assessment. Eventually, 79 articles were included in our study, including eight qualitative studies. An integrated approach was used to combine quantitative and qualitative studies into a single synthesis. Once all included studies were identified, a data-driven thematic analysis was performed.

Findings and Conclusions

Medical student participation in research is associated with improved short- and long- term scientific productivity, more informed career choices and improved knowledge about-, interest in- and attitudes towards research. Financial worries, gender, having a higher degree (MSc or PhD) before matriculation and perceived competitiveness of the residency of choice are among the factors that affect the engagement of medical students in research and/or their scientific productivity. Intercalated BSc degrees, mandatory graduation theses and curricular research components may help in standardizing research education during medical school.     

Predictive Markers for Postsurgical Medical Management of Acromegaly: A Systematic Review and Consensus Treatment Guideline

Objective: To clarify the selection of medical therapy following transsphenoidal surgery in patients with acromegaly, based on growth hormone (GH)/insulin-like growth factor 1 (IGF-1) response and glucometabolic control.Methods: We carried out a systematic literature review on three of the best studied and most practical predictive markers of the response to somatostatin analogues (SSAs): somatostatin receptor (SSTR) expression, tumor morphologic classification, and T2-weighted magnetic resonance imaging (MRI) signal intensity. Additional analyses focused on glucose metabolism in treated patients.Results: The literature survey confirmed significant associations of all three factors with SSA responsiveness. SSTR expression appears necessary for the SSA response; however, it is not sufficient, as approximately half of SSTR2-positive tumors failed to respond clinically to first-generation SSAs. MRI findings (T2-hypo-intensity) and a densely granulated phenotype also correlate with SSA efficacy, and are advantageous as predictive markers relative to SSTR expression alone. Glucometabolic control declines with SSA monotherapy, whereas GH receptor antagonist (GHRA) monotherapy may restore normoglycemia.Conclusion: We propose a decision tree to guide selection among SSAs, dopamine agonists (DAs), and GHRA for medical treatment of acromegaly in the postsurgical setting. This decision tree employs three validated predictive markers and other clinical considerations, to determine whether SSAs are appropriate first-line medical therapy in the postsurgical setting. DA treatment is favored in patients with modest IGF-1 elevation. GHRA treatment should be considered for patients with T2-hyperintense tumors with a sparsely granulated phenotype and/or low SSTR2 staining, and may also be favored for individuals with diabetes. Prospective analyses are required to test the utility of this therapeutic paradigm.Abbreviations: DA = dopamine agonist; DG = densely granulated; GH = growth hormone; GHRA = growth hormone receptor antagonist; HbA1c = glycated hemoglobin; IGF-1 = insulin-like growth factor-1; MRI = magnetic resonance imaging; SG = sparsely granulated; SSA = somatostatin analogue; SSTR = somatostatin receptor     

Safety of Levetiracetam in Paediatrics: A Systematic Review

Objective

To identify adverse events (AEs) associated with Levetiracetam (LEV) in children.

Methods

Databases EMBASE (1974-February 2015) and Medline (1946-February 2015) were searched for articles in which paediatric patients (≤18 years) received LEV treatment for epilepsy. All studies with reports on safety were included. Studies involving adults, mixed age population (i.e. children and adults) in which the paediatric subpopulation was not sufficiently described, were excluded. A meta-analysis of the RCTs was carried out and association between the commonly reported AEs or treatment discontinuation and the type of regimen (polytherapy or monotherapy) was determined using Chi² analysis.

Results

Sixty seven articles involving 3,174 paediatric patients were identified. A total of 1,913 AEs were reported across studies. The most common AEs were behavioural problems and somnolence, which accounted for 10.9% and 8.4% of all AEs in prospective studies. 21 prospective studies involving 1120 children stated the number of children experiencing AEs. 47% of these children experienced AEs. Significantly more children experienced AEs with polytherapy (64%) than monotherapy (22%) (p<0.001). Levetiracetam was discontinued in 4.5% of all children on polytherapy and 0.9% on monotherapy (p<0.001), the majority were due to behavioural problems.

Conclusion

Behavioural problems and somnolence were the most prevalent adverse events to LEV and the most common causes of treatment discontinuation. Children on polytherapy have a greater risk of adverse events than those receiving monotherapy.     

Patient-Reported Outcomes for Quality of Life Assessment in Atrial Fibrillation: A Systematic Review of Measurement Properties

BackgroundAtrial fibrillation is a large and growing burden across all types of healthcare. Both incidence and prevalence are expected to double in the next 20 years, with huge impact on hospital admissions, costs and patient quality of life. Patient wellbeing determines the management strategy for atrial fibrillation, including the use of rhythm control therapy and the clinical success of heart rate control. Hence, evaluation of quality of life is an emerging and important part of the assessment of patients with atrial fibrillation. Although a number of questionnaires to assess quality of life in atrial fibrillation are available, a comprehensive overview of their measurement properties is lacking.InterpretationGiven the low ratings for many measurement properties, no single questionnaire can be recommended, although AFEQT performed strongest. Further studies to robustly assess reliability, validity and responsiveness of AF-specific quality of life questionnaires are required. This review consolidates the current evidence for quality of life assessment in patients with atrial fibrillation and identifies priority areas for future research.     

Current Soviet Psychology: A Systematic Review

Scope and Nature of the Present Report: This presentation is based on materials, primarily books, that have become available since the completion of the chapter on "Recent Developments in Soviet Psychology," published in Vol. 15 of the Annual Review of Psychology (Brozek, 1964, pp. 493-594). It is closer to a commentary on Soviet contributions that are of potential interest to American psychologists (a "bibliography with comment") than to a critical appraisal. The latter is the task of topical reviews and monographic presentations.     

Electroacupuncture for Tinnitus: A Systematic Review

Background

Treatment effects of electroacupuncture for patients with subjective tinnitus has yet to be clarified.

Objectives

To assess the effect of electroacupuncutre for alleviating the symptoms of subjective tinnitus.

Methods

Extensive literature searches were carried out in three English and four Chinese databases (PubMed, EMBASE, Cochrane Library, CNKI, Wanfang Chinese Digital Periodical and Conference Database, VIP, and ChiCTR).The date of the most recent search was 1 June 2014. Randomized controlled trials (RCTs) or quasi-RCTs were included. The titles, abstracts, and keywords of all records were reviewed by two authors independently. The data were collected and extracted by three authors. The risk of bias in the trials was assessed in accordance with the Cochrane Handbook, version 5.1.0. (http://www.handbook.cochrane.org). Eighty-nine studies were retrieved. After discarding 84 articles, five studies with 322 participants were identified. Assessment of the methodological quality of the studies identified weaknesses in all five studies. All studies were judged as having a high risk of selection and performance bias. The attrition bias was high in four studies. Incompleteness bias was low in all studies. Reporting bias was unclear in all studies. Because of the limited number of trials included and the various types of interventions and outcomes, we were unable to conduct pooled analyses.

Conclusions

Due to the poor methodological quality of the primary studies and the small sample sizes, no convincing evidence that electroacupuncture is beneficial for treating tinnitus could be found. There is an urgent need for more high-quality trials with large sample sizes for the investigation of electroacupuncture treatment for tinnitus.     

A Systematic Review of Scope and Quality of Health Economic Evaluation Studies in Vietnam

Introduction

The application of health economic evaluation (HEE) evidence can play an important role in strategic planning and policy making. This study aimed to assess the scope and quality of existing research, with the goal of elucidating implications for improving the use of HEE evidence in Vietnam.

Methods

A comprehensive search strategy was developed to search medical online databases (Medline, Google Scholar, and Vietnam Medical Databases) to select all types of HEE studies except cost-only analyses. Two researchers assessed the quality of selected studies using the Quality of Health Economic Studies (QHES) instrument.

Results

We selected 26 studies, including 6 published in Vietnam. The majority of these studies focused on infectious diseases (14 studies), with HIV being the most common topic (5 studies). Most papers were cost-effectiveness studies that measured health outcomes using DALY units. Using QHES, we found that the overall quality of HEE studies published internationally was much higher (mean score 88.7+13.3) than that of those published in Vietnam (mean score 67.3+22.9). Lack of costing perspectives, reliable data sources and sensitivity analysis were the main shortcomings of the reviewed studies.

Conclusion

This review indicates that HEE studies published in Vietnam are limited in scope and number, as well as by several important technical errors or omissions. It is necessary to formalize the process of health economic research in Vietnam and to institutionalize the links between researchers and policy-makers. Additionally, the quality of HEE should be enhanced through education about research techniques, and the implementation of standard HEE guidelines.     

Neurobiological Correlates in Forensic Assessment: A Systematic Review

Background

With the increased knowledge of biological risk factors, interest in including this information in forensic assessments is growing. Currently, forensic assessments are predominantly focused on psychosocial factors. A better understanding of the neurobiology of violent criminal behaviour and biological risk factors could improve forensic assessments.

Objective

To provide an overview of the current evidence about biological risk factors that predispose people to antisocial and violent behaviour, and determine its usefulness in forensic assessment.

Methods

A systematic literature search was conducted using articles from PsycINFO, Embase and Pubmed published between 2000 and 2013.

Results

This review shows that much research on the relationship between genetic predisposition and neurobiological alterations with aggression is performed on psychiatric patients or normal populations. However, the number of studies comparing offenders is limited. There is still a great need to understand how genetic and neurobiological alterations and/or deficits are related to violent behaviour, specifically criminality. Most studies focus on only one of the genetic or neurobiological fields related to antisocial and/or violent behaviour. To reliably correlate the findings of these fields, a standardization of methodology is urgently needed.

Conclusion

Findings from the current review suggest that violent aggression, like all forms of human behaviour, both develops under specific genetic and environmental conditions, and requires interplay between these conditions. Violence should be considered as the end product of a chain of life events, during which risks accumulate and potentially reinforce each other, displaying or triggering a specific situation. This systematic review did not find evidence of predispositions or neurobiological alterations that solely explain antisocial or violent behaviour. With better designed studies, more correlation between diverse fields, and more standardisation, it might be possible to elucidate underlying mechanisms. Thus, we advocate maintaining the current case-by-case differentiated approach to evidence-based forensic assessment.     

Cytocompatibility of Medical Biomaterials Containing Nickel by Osteoblasts: a Systematic Literature Review

The present review is based on a survey of 21 studies on the cytocompatibility of medical biomaterials containing nickel, as assessed by cell culture of human and animal osteoblasts or osteoblast-like cells. Among the biomaterials evaluated were stainless steel, NiTi alloys, pure Ni, Ti, and other pure metals. The materials were either commercially available, prepared by the authors, or implanted by various techniques to generate a protective layer of oxides, nitrides, acetylides. The observation that the layers significantly reduced the initial release of metal ions and increased cytocompatibility was confirmed in cell culture experiments. Physical and chemical characterization of the materials was performed. This included, e.g., surface characterization (roughness, wettability, corrosion behavior, quantity of released ions, microhardness, and characterization of passivation layer). Cytocompatibility tests of the materials were conducted in the cultures of human or animal osteoblasts and osteoblast-like cells. The following assays were carried out: cell proliferation and viability test, adhesion test, morphology (by fluorescent microscopy or SEM). Also phenotypic and genotypic markers were investigated. In the majority of works, it was found that the most cytocompatible materials were stainless steel and NiTi alloy. Pure Ni was rendered and less cytocompatible. All the papers confirmed that the consequence of the formation of protective layers was in significant increase of cytocompatibility of the materials. This indicates the possible further modifications of the manufacturing process (formation of the passivation layer).     

Cognition of and Demand for Education and Teaching in Medical Statistics in China: A Systematic Review and Meta-Analysis

BackgroundAlthough a substantial number of studies focus on the teaching and application of medical statistics in China, few studies comprehensively evaluate the recognition of and demand for medical statistics. In addition, the results of these various studies differ and are insufficiently comprehensive and systematic.ObjectivesThis investigation aimed to evaluate the general cognition of and demand for medical statistics by undergraduates, graduates, and medical staff in China.MethodsWe performed a comprehensive database search related to the cognition of and demand for medical statistics from January 2007 to July 2014 and conducted a meta-analysis of non-controlled studies with sub-group analysis for undergraduates, graduates, and medical staff.ResultsThere are substantial differences with respect to the cognition of theory in medical statistics among undergraduates (73.5%), graduates (60.7%), and medical staff (39.6%). The demand for theory in medical statistics is high among graduates (94.6%), undergraduates (86.1%), and medical staff (88.3%). Regarding specific statistical methods, the cognition of basic statistical methods is higher than of advanced statistical methods. The demand for certain advanced statistical methods, including (but not limited to) multiple analysis of variance (ANOVA), multiple linear regression, and logistic regression, is higher than that for basic statistical methods. The use rates of the Statistical Package for the Social Sciences (SPSS) software and statistical analysis software (SAS) are only 55% and 15%, respectively.ConclusionThe overall statistical competence of undergraduates, graduates, and medical staff is insufficient, and their ability to practically apply their statistical knowledge is limited, which constitutes an unsatisfactory state of affairs for medical statistics education. Because the demand for skills in this area is increasing, the need to reform medical statistics education in China has become urgent.     

The Jarisch-Herxheimer Reaction in Leptospirosis: A Systematic Review

Background

Leptospirosis is an endemo-epidemic zoonotic disease associated with potentially fatal renal, cardiovascular or pulmonary failure. Recommended treatment includes antibiotics, which may induce a Jarisch-Herxheimer reaction (JHR). Since little information on the importance of this adverse event is available, we performed this review to quantify frequency and impact of JHR in leptospirosis management.

Methodology/Principal Findings

This review systematically summarizes the literature on the JHR in leptospirosis. To approach the broader aspects of the subject, articles considering the treatment of leptospirosis, national leptospirosis guidelines and textbook and technical reports of the World Health Organisation were reviewed. Publications describing JHR in leptospirosis are very limited and consist mainly of single case reports and small case series. A single randomized control trial specifically assessed the JHR occurrence, but it has never been systematically investigated in large trials. Not all guidelines and not all literature on leptospirosis mention this reaction which can be fatal.

Conclusions/Significance

Although generally assumed to be a rare event, the true prevalence of JHR in leptospirosis is unknown and the awareness of this event is insufficient. All leptospirosis guidelines and local leptospirosis protocols should stress on systematic monitoring for clinical status early after antibiotic administration. Large well designed studies are required to precise the incidence and the impact of JHR as well as the severity and rates between various antibiotics.