Introducing the Library of Guidance for Health Scientists (LIGHTS): A Living Database for Methods Guidance.

Importance: Improving methodological quality is a priority in the health research community. Finding appropriate methods guidance can be challenging due to heterogeneous terminology, poor indexing in medical databases, and variation in formats. The Library of Guidance for Health Scientists (LIGHTS) is a new searchable database for methods guidance articles. Observations: Journal articles that aim to provide guidance for performing (including planning, design, conduct, analysis, and interpretation), reporting, and assessing the quality of health-related research involving humans or human populations (ie, excluding basic and animal research) are eligible for LIGHTS. A team of health researchers, information specialists, and methodologists continuously identifies and manually indexes eligible guidance documents. The search strategy includes focused searches of specific journals, specialized databases, and suggestions from researchers. A current limitation is that a keyword-based search of MEDLINE (and other general databases) and manual screening of records were not feasible because of the large number of hits (n = 915 523). As of September 20, 2022, LIGHTS included 1246 articles (336 reporting guidelines, 80 quality assessment tools, and 830 other methods guidance articles). The LIGHTS website provides a user-oriented search interface including filters for study type, specific methodological topic, research context, guidance type, and development process of the guidance. Automated matching of alternative methodological expressions (eg, enter loss to follow-up and find articles indexed with missing data) enhances search queries. Conclusions and Relevance: LIGHTS is a peer-supported initiative that is intended to increase access to and use of methods guidance relevant to health researchers, statisticians, methods consultants, methods developers, ethics boards, peer reviewers, journal editors, and funding bodies.

HLA-associated adverse drug reactions - scoping review.

Alleles of the human leukocyte antigen (HLA) system have been associated with the occurrence of idiosyncratic adverse drug reactions (ADRs). Accordingly, it is assumed that pre-emptive testing for the presence of certain HLA alleles (HLA-typing) could prevent these ADRs in carriers. In order to perceive the current evidence for HLA-associated ADRs, we conducted a scoping review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The literature search on PubMed and on Embase was carried out on the July 8 and 9, 2020, respectively. To be included in the scoping review, the studies had to investigate an association of any HLA-associated ADR with any small molecule approved and available on the Swiss market. We considered English and German primary literature published since 2002. A total of 149 studies were included, whereof most were retrospective, whereas one was a prospective randomized controlled trial. The majority of the studies (n = 33) described the association of HLA-B*15:02 with carbamazepine. It was not possible to directly compare the studies, as they were too heterogeneous in terms of the ADR definition, the HLA alleles, the number of participants, and the study types. Therefore, we summarized the results in a descriptive manner. Even if an interpretation of the outcomes remains open, the descriptive overview revealed the prevailing complexity and uncertainty in the field. For the future, consistent definitions on the different phenotypes need to be established and applied and the reporting of association studies should follow a harmonized structure.

[Four numbers and a bit more basic knowledge of mathematics]. / Vier Zahlen und noch ein bisschen mehr Mathe. Der Unterschied zwischen Chance und Risiko.

In addition to relative risk, relative risk reduction and absolute risk reduction there circulates another effect size for binary endpoints in the scientific medical literature: the odds ratio. Relative risk and odds ratio are alternative ways of reflecting study results. Both, relative risk (RR) and odds ratio (OR), can easily be calculated from the "2 x 2-table". Advantage of OR: odds ratios can be calculated in every type of controlled study design, including retrospective studies. Furthermore, odds ratios--the biostatisticians are swarming--offer beautiful mathematical properties and therefore are often used in meta-analysis as an effect size for calculating a pooled estimate of the results of different studies with the same clinical question. Disadvantage of OR: In clinical studies the presentation of the results as "odds ratios" may result in an overestimation of the intervention effect. This article shows the difference between ""chance" and "risk" and how odds ratio and relative risk are associated.

[Four numbers and basic knowledge of mathematics]. / Vier Zahlen und ein bisschen Mathe. Das Einmaleins zum Berechnen von Effektmassen.

Results of clinical trials are presented in different expressions of risks: baseline risk, relative risk (RR), relative risk reduction (RRR), absolute risk reduction (ARR), or risk difference (RD). In this article of our series about the basics of evidence-based medicine we show how results of clinical trials are calculated based on the 2 x 2-table. The 2 x 2-table usually contains all information needed to calculate the main study results. Adequate interpretation of the results/treatment effects is the basis for evidence-based advices in pharmaceutical practice.

[About the certainty of study results. What p-value and confidence intervalls tell us on it]. / Uber die Sicherheit von Studenergebnossen. Was uns p-Wert und Konfidenzintervall verraten.

In clinical trials data of individuals are collected, who are subjected to different treatments under controlled conditions. These studies investigate differences between interventions, and their results--provide the basis for clinical decision making in individuals or for policy decisions concerning entire patient populations. This requires reliable results. How confident a result of the study actually is, is illustrated by using various statistical parameters: p-value or confidence interval. What these parameters are and how to interpret them, is the objective of this article.

[The number needed to treat (NNT) and the number needed to harm (NNH)]. / Number needed to treat (NNT) und Number needed to harm (NNH). Weitere Abkömmlinge der Vier-Felder-Tafel.

In our previous articles we introduced the relative and absolute expressions of risk: baseline risk, relative risk (RR), relative risk reduction (RRR), absolute risk reduction (ARR), or risk difference (RD). The "number needed to xy" is another concept to describe the results of a clinical trial. Depending on the investigated problem the "number needed to xy" is the "number needed to treat", the "number needed to harm", the "number needed to vaccinate", or the "number needed to screen". In this article of our series we introduce the number needed to treat (NNT) and the number needed to harm (NNH) as a method to characterize the difference of two compared therapy options. As the other effect sizes the NNT and NNH can be used to inform patients about the expected benefit (or harm) of different therapy options.

[The information flood--a multicomponent mixture. Analytical methods for the extraction of valid information]. / Die Informationsflut--ein Vielstoffgemisch. Die analytischen Methoden zur Extraktion valider Informationen.

Over the centuries some individual scientists have challenged their knowledge, believes and behaviour. The common knowledge developed very fast, but the challenge still remains to ask the question "what do we really know"? And "what is the basis of our decisions and recommendations?" The scattered individual efforts finally advanced to a consolidated methodology--known as "evidence based medicine". This is the first article of a series to get German speaking pharmacists familiar with the basic concepts of evidence based methodology. The series gives some examples how the concept of evidence based medicine can be implemented in pharmaceutical practice.

Effect of drug reminder packaging on medication adherence: a systematic review revealing research gaps.

BACKGROUND: This was a systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Evidence mapping was used to reveal the effect of drug reminder packaging on medication adherence, to identify research gaps and to make suggestions for future research. METHODS: PubMed, Embase, CINAHL and PsycINFO were searched with an end date of September 2013 using the Medical Subject Headings (MeSH) term 'medication adherence' and 20 different search terms for 'drug reminder packaging', limited to the English and German languages. Additional references were identified through cross-referencing. All prospective controlled trials with an intervention using drug reminder packaging for patients taking at least one medication without the assistance of a health-care professional were included in the evidence mapping of the effect of drug reminder packaging on adherence and outcomes according to the Economic, Clinical and Humanistic Outcomes (ECHO) model. RESULTS: A total of 30 studies met the inclusion criteria: 10 randomized controlled trials, 19 controlled clinical trials and 1 cohort study. Drug reminder packaging had a significant effect on at least one adherence parameter in 17 studies (57%). The methodological quality was strong in five studies. Two studies provided complete information. Clear research gaps emerged. CONCLUSIONS: Overall, the studies showed a positive effect of drug reminder packaging on adherence and clinical outcomes. However, poor reporting and important gaps like missing humanistic and economic outcomes and neglected safety issues limit the drawing of firm conclusions. Suggestions are made for future research.

[Evidence-based pharmacy--assessment of study quality]. / Qualitätsbewertung klinischer Studien. Wie man die Spreu vom Weizen trennt.

After having identified relevant studies through a literature search for a specific question, it is now necessary to consider the trustworthiness of the publications found. This article deals with the quality assessment of the raw material "information". The focus is based on the following questions: (a) Why is the randomized controlled trial (RCT) the gold standard for proving a cause-effect relationship? (b) What types of biases exist? To identify the risk of bias, it is necessary to become familiar with some terms. The aim of the current paper is to clarify and explain the key points for the assessment of internal validity of RCTs. The underlying question is: Can I trust the results of this study at all? And: Is it worthwhile to read further? In addition, an example of how to structure a "critical appraisal" will be shown. For this purpose, checklists are helpful to systematize and document the procedure.

[Navigation aid through the information overload]. / Navigationshilfe durch die Informationsfluten.

We live in the modern information society. "To be informed" has a crucial impact on the personal, professional, economic and social development. The knowledge of things and their relationships is essential for acute decisions as well as for long-term planning. And at no time it was easier to get the information required within shorter time periods--no matter to whatsoever. The offer of information of the World Wide Web is inexhaustible. This also applies to information about all possible therapeutic and pharmaceutical issues. But is the information found reliable, too? And are easily accessible sources credible? Can we deal with the information overload at these days or do we actually risk paddling only on the surface of the "information-sea", without ever perceiving the actual information depth and width, less to use it? How can we protect being taken in by marketing strategies? The present article describes a structured proceed when seeking literature to find useful medical and pharmaceutical information in a time saving manner.

[Evidence-based pharmacy - Assessement of quality and clinical relevance of study results]. / Qualitätsbewertung klinischer Studien. Ergebnisqualität: Wie man die Spreu vom Weizen trennt (Teil 2).

The critical appraisal of a study publication includes several steps: quality inspection of the study methodology, examination of the results, assessments of benefit and harm for the individual patient. If the first step of the "critical appraisal" determines, that different sources of bias were successfully eliminated or minimized in the study conduct, it is worthwhile to work through the article completely. In the second step, the size and confidence of the study results have to be examined in detail. Different outcome measures are used to describe the effect of an intervention in clinical trials. However, not all endpoints studied, or differences that are found between treatment groups, are important for the decision making of a patient. In the last step, the study results are interpreted for the individual patient in terms of the expected ben- efits and possible harms. While the control of methodical quality and the effect size of study outcomes may be based on formal criteria, professional value judgement is necessary for the transfer of study results to an individual patient, by which a recommendation can be made, adapted to the individual circumstances, needs and expectations of the patient.

How can we teach EBM in clinical practice? An analysis of barriers to implementation of on-the-job EBM teaching and learning.

INTRODUCTION: Evidence-based medicine (EBM) improves the quality of health care. Courses on how to teach EBM in practice are available, but knowledge does not automatically imply its application in teaching. We aimed to identify and compare barriers and facilitators for teaching EBM in clinical practice in various European countries. METHODS: A questionnaire was constructed listing potential barriers and facilitators for EBM teaching in clinical practice. Answers were reported on a 7-point Likert scale ranging from not at all being a barrier to being an insurmountable barrier. RESULTS: The questionnaire was completed by 120 clinical EBM teachers from 11 countries. Lack of time was the strongest barrier for teaching EBM in practice (median 5). Moderate barriers were the lack of requirements for EBM skills and a pyramid hierarchy in health care management structure (median 4). In Germany, Hungary and Poland, reading and understanding articles in English was a higher barrier than in the other countries. CONCLUSION: Incorporation of teaching EBM in practice faces several barriers to implementation. Teaching EBM in clinical settings is most successful where EBM principles are culturally embedded and form part and parcel of everyday clinical decisions and medical practice.

How are "teaching the teachers" courses in evidence based medicine evaluated? A systematic review.

BACKGROUND: Teaching of evidence-based medicine (EBM) has become widespread in medical education. Teaching the teachers (TTT) courses address the increased teaching demand and the need to improve effectiveness of EBM teaching. We conducted a systematic review of assessment tools for EBM TTT courses. To summarise and appraise existing assessment methods for teaching the teachers courses in EBM by a systematic review. METHODS: We searched PubMed, BioMed, EmBase, Cochrane and Eric databases without language restrictions and included articles that assessed its participants. Study selection and data extraction were conducted independently by two reviewers. RESULTS: Of 1230 potentially relevant studies, five papers met the selection criteria. There were no specific assessment tools for evaluating effectiveness of EBM TTT courses. Some of the material available might be useful in initiating the development of such an assessment tool. CONCLUSION: There is a need for the development of educationally sound assessment tools for teaching the teachers courses in EBM, without which it would be impossible to ascertain if such courses have the desired effect.

Pharmacokinetics and pharmacodynamics of nasally delivered midazolam.

AIMS: To investigate the pharmacokinetics and pharmacodynamics of nasal formulations containing midazolam (5-30 mg ml(-1)) complexed with cyclodextrin. METHODS: An open-label sequential trial was conducted in eight healthy subjects receiving single doses of 1 mg and 3 mg intranasally and 1 mg midazolam intravenously. Pharmacokinetic parameters were obtained by non-compartmental and two-compartmental models. Pharmacodynamic effects of midazolam were assessed using VAS and a reaction time test. RESULTS: Mean bioavailability of midazolam after nasal administration ranged from 76 +/- 12% to 92 +/- 15%. With formulations delivering 1 mg midazolam, mean C(max) values between 28.1 +/- 9.1 and 30.1 +/- 6.6 ng ml(-1) were reached after 9.4 +/- 3.2-11.3 +/- 4.4 min. With formulations delivering 3 mg midazolam, mean C(max) values were between 68.9 +/- 19.8 and 80.6 +/- 15.2 ng ml(-1) after 7.2 +/- 0.7-13.0 +/- 4.3 min. Chitosan significantly increased C(max) and reduced t(max) of midazolam in the high-dose formulation. Mean ratios of dose-adjusted AUC after intranasal and intravenous application for 1'-hydroxymidazolam were between 0.97 +/- 0.15 and 1.06 +/- 0.24, excluding relevant gastrointestinal absorption of intranasal midazolam. The pharmacodynamic effects after the low-dose nasal formulations were comparable with those after 1 mg intravenous midazolam. The maximum increase in reaction time by the chitosan-containing formulation delivering 3 mg midazolam was greater compared with 1 mg midazolam i.v. (95 +/- 78 ms and 19 +/- 22 ms, mean difference 75.5 ms, 95% CI 15.5, 135.5, P < 0.01). Intranasal midazolam was well tolerated but caused reversible irritation of the nasal mucosa. CONCLUSIONS: Effective midazolam serum concentrations were reached within less than 10 min after nasal application of a highly concentrated midazolam formulation containing an equimolar amount of the solubilizer RMbetaCD combined with the absorption enhancer chitosan.

Teaching trainers to incorporate evidence-based medicine (EBM) teaching in clinical practice: the EU-EBM project.

BACKGROUND: Evidence based medicine (EBM) is considered an integral part of medical training, but integration of teaching various EBM steps in everyday clinical practice is uncommon. Currently EBM is predominantly taught through theoretical courses, workshops and e-learning. However, clinical teachers lack confidence in teaching EBM in workplace and are often unsure of the existing opportunities for teaching EBM in the clinical setting. There is a need for continuing professional development (CPD) courses that train clinical trainers to teach EBM through on-the-job training by demonstration of applied EBM real time in clinical practice. We developed such a course to encourage clinically relevant teaching of EBM in post-graduate education in various clinical environments. METHODS: We devised an e-learning course targeting trainers with EBM knowledge to impart educational methods needed to teach application of EBM teaching in commonly used clinical settings. The curriculum development group comprised experienced EBM teachers, clinical epidemiologists, clinicians and educationalists from institutions in seven European countries. The e-learning sessions were designed to allow participants (teachers) to undertake the course in the workplace during short breaks within clinical activities. An independent European steering committee provided input into the process. RESULTS: The curriculum defined specific learning objectives for teaching EBM by exploiting educational opportunities in six different clinical settings. The e-modules incorporated video clips that demonstrate practical and effective methods of EBM teaching in everyday clinical practice. The course encouraged focussed teaching activities embedded within a trainer's personal learning plan and documentation in a CPD portfolio for reflection. CONCLUSION: This curriculum will help senior clinicians to identify and make the best use of available opportunities in everyday practice in clinical situations to teach various steps of EBM and demonstrate their applicability to clinical practice. Once fully implemented, the ultimate outcome of this pilot project will be a European qualification in teaching EBM, which will be used by doctors, hospitals, professional bodies responsible for postgraduate qualifications and continuing medical education.

How far did we get? How far to go? A European survey on postgraduate courses in evidence-based medicine.

BACKGROUND: Over the past decade, evidence-based medicine (EBM) has gained recognition as a means to improve the quality of health care provision. However, little is known about learning opportunities to acquire EBM-associated skills. The EUebm-Unity partnership explored current educational activities for EBM practice for doctors across Europe. METHODS: We surveyed organizations offering postgraduate EBM courses across Europe inquiring about their course programme, teaching content and strategies, and interest in a Europe-wide curriculum in EBM. RESULTS: One hundred and fifty-six organizers in eight European countries reported 403 courses that had started first-time from 1996 to 2006. Despite a steady increase, in absolute terms, the frequency of courses was low and varied from 1 first-time offering of a course per 640 doctors (Spain) to 1 first-time offering per 5600 doctors (Austria) over 10 years. Most adopted the McMaster EBM teaching concept of small group, problem-based learning focussing on interventions, diagnostic tests and guidelines, and included efforts to link EBM to patient care. Teaching staff consisted of doctors from academic and non-academic settings, supported by methodologists. Efforts to formally integrate EBM in postgraduate activities were only partially successful. Most organizations welcomed a standardized European qualification in EBM. A limitation of the survey is the lack of follow-up information about the continuation of courses following the first-time offering. CONCLUSIONS: All countries offer some EBM courses with varying teaching intensity. Learning opportunities are insufficient to ensure widespread dissemination of knowledge and skills. Most countries welcome more efforts to develop inexpensive and feasible educational activities at a postgraduate level.

Multicenter trial: comparison of two different formulations and application systems of low-dose nasal midazolam for routine magnetic resonance imaging of claustrophobic patients.

PURPOSE: To prospectively assess and compare two formulations and methods of administration of low-dose nasal midazolam for the treatment of claustrophobic patients undergoing magnetic resonance imaging (MRI) as part of a multicenter Phase III trial. MATERIALS AND METHODS: In all, 108 consecutive adult claustrophobic patients were randomly assigned to one of two treatment groups (multidose group: MDG, unit-dose group: UDG). MDG encompassed 55 patients who received intranasally a 0.5% midazolam formulation into each nostril (total dose, 1.0 mg), whereas the 53 patients in UDG received a 1% midazolam formulation into only one nostril (total dose, 1.0 mg). This initial dose could be repeated once. Patient tolerance and anxiety were assessed using a questionnaire and a visual analog scale immediately before and after MRI. Image quality was evaluated using a five-point scale. RESULTS: In all, 53/55 MR examinations (96%) with MDG and 52/53 (98%) with UDG were completed successfully. The dose of 1 mg had to be repeated significantly less often in UDG compared to MDG (4/53, 8% vs. 13/55, 24%; P = 0.003). The image quality of all MR examinations was rated good to excellent, and slightly better in UDG (P = 0.045). CONCLUSION: Nasally applied low-dose midazolam is a patient-friendly solution to facilitate MRI of claustrophobic patients. The nasal spray of UDG is superior to that of MDG with a necessity of additional dosing.

Preservative-free triamcinolone acetonide suspension developed for intravitreal injection.

OBJECTIVES: All commercially available triamcinolone acetonide (TACA) suspensions, used for intravitreal treatment, contain retinal toxic vehicles (e.g., benzyl alcohol, solubilizer). Our aim was to find a convenient and reproducible method to compound a completely preservative-free TACA suspension, adapted to the intraocular physiology, with consistent quality (i.e., proven sterility and stability, constant content and dose uniformity, defined particle size, and 1 year shelf life). METHODS: We evaluated two published (Membrane-filter, Centrifugation) and a newly developed method (Direct Suspending) to compound TACA suspensions for intravitreal injection. Parameters as TACA content (HPLC), particle size (microscopy and laser spectrometry), sterility, and bacterial endotoxins were assessed. Stability testing (at room temperature and 40 degrees C) was performed: color and homogeneity (visually), particle size (microscopically), TACA content and dose uniformity (HPLC) were analyzed according to International Conference on Harmonisation guidelines. RESULTS: Contrary to the known methods, the direct suspending method is convenient, provides a TACA suspension, which fulfills all compendial requirements, and has a 2-year shelf life. CONCLUSIONS: We developed a simple, reproducible method to compound stable, completely preservative-free TACA suspensions with a reasonable shelf-life, which enables to study the effect of intravitreal TACA--not biased by varying doses and toxic compounds or their residues.