Dirk Moßhammer

Mechanisms and assessment of statin-related muscular adverse effects.

Statin‐associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life‐threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin‐related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450‐mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers.

Cooperation between general practitioners and occupational health physicians in Germany: how can it be optimised? A qualitative study

PurposeGeneral practitioners (GPs) and occupational health physicians (OPs) have several overlapping work fields, such as important functions in prevention, rehabilitation and reintegration into the workplace. In Germany, however, cooperation between GP and OP is often lacking or suboptimal. In this article, we analysed the suggestions for optimisation of cooperation.MethodsThree focus groups were interviewed: GP, OP and medical doctors working in both fields. A qualitative content analysis was performed.ResultsCategories of suggestions could be assigned to five issues: the “Systemic View” concerning the state and/or employer (e.g. the system of remuneration for GPs), “Inter-collegial Contact” (e.g. fostering “friendly exchanges” between both groups), “Medical Education” (e.g. introducing joint quality circles), “Contents of both Specialities” (e.g. necessity of communicating respective contents and competences), and “Patient-centred Care” (e.g. reintegration into workplace after longer periods of illness). The optimisation of cooperation was considered necessary by the OPs, whereas its necessity was sometimes questioned in the GPs’ group.ConclusionIn many aspects, the present data agree with results of studies from other countries addressing the cooperation between GPs and OPs and/or other specialists. Many suggestions obtained in this study are practical and could be implemented into daily routine. Future quantitative research is required to better assess the relative weight of the suggestions presented here.

Research tasks as part of the general practice clerkship in undergraduate medical education - a pilot project on feasibility and acceptance.

Abstract Objective: To assess the integration of a research task performed by students during their two-week clerkship in general practice. Methods: Students were assigned to interview five patients with coronary heart disease using a standardised questionnaire focusing on potential interaction of medications with statins. Acceptance and feasibility was assessed by means of a questionnaire survey of teaching physicians (n = 20) and students (n = 20). Results: According to most teaching physicians and students the recruitment of patients during the two-week clerkship was possible, and the practice work flow was not disturbed by the project. Both groups considered the research task on the documentation of potential drug interactions with statins as suitable. According to the teaching physicians the project had a learning effect for the students. In contrast, the students graded their learning effect less highly between ‘satisfactory’ and ‘sufficient’. The overall assessment of the project by the students was on average ‘satisfactory’ and differed from the assessment by the teaching physicians (‘good’). Conclusions: Adequate informing of students and participating physicians about the nature of the project and presenting preliminary results of the data in a plenary session at the end of the clerkship are essential for the acceptance of such projects.

Students' performing of practical research tasks for their scientific qualification - an approach within the family practice internship in undergraduate education.

Background: Future physicians should be educated in evidence-based medicine. So it is of growing importance for medical students to acquire both practical medical and basic research competencies. However, possibilities and concepts focusing on the acquisition of basic practical research competencies during undergraduate medical studies in Germany are rare. Therefore the aim of this article is to develop a didactic and methodological concept for research-based teaching and learning based on the initial results from the block placement in general practice. Methods: Connecting medical didactic approaches with classic educational control measures (knowledge, acceptance and transfer evaluation, process evaluation, and outcome evaluation). Results: We describe the steps for implementing a research task into the block placement in general practice. Also stressed is the need to develop didactic material and the introduction of structural changes. Furthermore, these steps are integrated with the individual educational control measures. A summary serves to illustrate the learning and teaching concept (Block Placement Plus). Conclusion: The conceptualisation of the Block Placement Plus leads to changes in the daily life routine of medical education during the undergraduate block placement in general practice. The concept can in principle be transferred to other courses. It may serve as an instrument for teachers within the framework of a longitudinal curriculum for the scientific qualification of medical students.

Pairs of Creatine Kinase Serum Activity

Background: For patients with an increased risk of developing myopathy with statin treatment, guidelines rec- ommend to measure CK before and 6-12 weeks after initiating statin treatment. Further, in clinical trials of statins, the number of patients experiencing elevated creatine kinase (CK) serum activity is commonly reported as a safety parameter. Usually exceeding the upper limit of normal (ULN) is used as the basis of description to characterize muscular damage potentially caused by statins. Therefore, basic data on both, proportions of patients with specific CK increases, and abso- lute and relative CK increases, would be helpful to assess potential CK chances in patients. However, no such data are available so far. Methods: CK activity was measured in a group of blood donors (n=40) at two occasions 10 weeks apart. The 95 th percen- tile of absolute and relative CK increases was selected to separate true from irrelevant changes. A CK difference was de- fined to be true if a random measurement error of 10% was exceeded. The numbers of subjects with true CK differences were characterised by both measurements being under, crossing, or being above ULN, and twice ULN, respectively. Results: Five percent of subjects (95 th percentile) had an increase of CK more than 139% (men) or 120% (women), re- spectively, as compared with the first measurement. Five percent of subjects had an absolute difference of at least 94 U/l (men) and 16 U/l (women), respectively. Thirty-one percent of subjects had both CK activities below 2 times the ULN. Six percent of them had the first measurement under and the second above ULN. In three percent, the first measurement was under and the second above 2 times the ULN. In no subject, the first and the second measurement was above 2 times the ULN. Conclusion: It is concluded that CK serum activity substantially varies between two measurements. The present data pro- vide the basis for developing reference ranges of CK activity pairs by simple variables that can be useful for practitioners and trialists.

Der feste Patientenstamm als potentielle Fallgrube prospektiver Studien im primärärztlichen Sektor

ZusammenfassungHintergrund und Ziel:Die Transparent- und Bekanntmachung von Studienproblemen können die Planung und Durchführung von Hausarztstudien enorm bereichern. Unter Einbeziehung der Studienteilnehmer ist es möglich, etwaige Studienproblempunkte genauer zu eruieren. Ziel der vorliegenden qualitativen Untersuchung war es deshalb, anhand einer Nachbefragung der beteiligten Hausärzte die Ursachen unerwarteter Studienergebnisse einer longitudinalen Interventionsstudie mit zwei Erhebungszeitpunkten herauszufinden. Zu beiden Zeitpunkten jener Studie wurden jeweils 2 400 Patienten einer Screeninguntersuchung zu alkoholbezogenen Gesundheitsstörungen unterzogen.Methodik:Es wurden retrospektiv Telefoninterviews mit 39 der insgesamt 43 an obiger Studie beteiligten Hausärzte durchgeführt. Die Auswertung erfolgte inhaltsanalytisch nach der Qualitativen Inhaltsanalyse von Philipp Mayring.Ergebnisse:Die Hausärzte erwähnten aus der Literatur bekannte Problempunkte als Ursachen für die unerwarteten Ergebnisse: der hohe Dokumentationsaufwand, das tabuisierte Studienthema und die Motivationsminderung zum Studienende. Eine weitere Ursache wurde aufgegriffen: der wiederholte Rekrutierungsablauf dieser Interventionsstudie. Es herrschte Unklarheit darüber, ob Patienten vom ersten Erhebungszeitpunkt auch beim zweiten eingeschlossen werden durften. Zudem scheint der sich wenig verändernde Patientenstamm in der Hausarztpraxis ein Hauptgrund gewesen zu sein; demnach konnten zum zweiten Erhebungszeitpunkt der Studie nur wenige neue Patienten eingeschlossen werden.Schlussfolgerung:Für die Planung von Studien mit wiederholten Durchläufen sowie chronischen und tabuisierten Erkrankungen muss die spezielle Situation in der Hausarztpraxis mit bekanntem und festem Patientenstamm, der sich sogar innerhalb von Jahren nur wenig ändert, berücksichtigt werden. Die hier erörterten Ursachen für Rekrutierungsprobleme von Patienten können wichtig sein, um selektionsbedingte Fehler bei hausärztlichen Studien zu vermeiden.AbstractBackground and Purpose:Transparency and disclosure of problems in primary health-care studies can add enormous information to the planning and conduction of such studies. By means of the inquiry of study participants, important data on study problems can be found out. Therefore, the aim of this qualitative study was to identify the causes of unexpected results of an intervention study in general practitioners’ (GPs) practices by means of an inquiry of the participating GPs. The very study was about diagnosing alcohol- related health disorders at two points of time 1 year apart each with 2,400 primary health-care patients.Methods:39 of the 43 participating GPs of the study mentioned were asked by telephone about the possible causes of the unexpected study results. Data analysis was conducted according to the Qualitative Content Analysis of Philipp Mayring.Results:The GPs mentioned problems that are already described in the international literature: the high expenses for study documentation, tabooed health topics, and declining participation motivation at the end of the study. A further cause of the unexpected study results was picked up: the repeated patient recruitment of this intervention study. It was unclear for the GPs whether they could include the same patients at the first and second recruitment point of time. Moreover, one main reason for the unexpected study results seems to be the stable patient collective of GPs’ practices; according to that, only few new patients could be included at the second time point of recruitment.Conclusion:In primary health-care research requiring several time points for patient recruitment, one has to consider potential tabooed health topics and the special situation in primary health-care practices. This situation is characterized by a stable amount of known patients, even over years. The here-discussed causes of recruitment problems might be essential to avoid selection bias in primary health-care studies.

Physical examination in undergraduate medical education in the field of general practice – a scoping review

BackgroundPhysical examination (PE) is an essential clinical skill and a central part of a physician’s daily activity. Teaching of PE has been integrated into medical school by many clinical disciplines with respective specific examination procedures. For instance, PE teaching in general practice may include a full-body examination approach. Studies show that PE-skills of medical students often need enhancement. The aim of this article was to scope the literature regarding the teaching and research of PE within general practice during undergraduate medical education. We evaluated a wide breadth of literature relating to the content, study design, country of research institution and year of publication.MethodsLiterature search in Medline along the PRISMA-P protocol was performed by search syntax (“physical examination” AND “medical education” AND “undergraduate” AND general practice) considering Medline MeSH (Medical Subject Heading)-Terms and Medline search term tree structure. Independent title, abstract and full-text screening with defined inclusion and exclusion criteria was performed. Full texts were analyzed by publication year, country of origin, study design and content (by categorizing articles along their main topic according to qualitative content analysis of Mayring).ResultsOne-hundred seven articles were included. The annual number of publications ranged from 4 to 14 and had a slightly rising trend since 2000. Nearly half of the publications originated from the United States (n = 54), 33 from Canada and the United Kingdom. Overall, intervention studies represented the largest group (n = 60, including uncontrolled and controlled studies, randomized and non-randomized), followed by cross-sectional studies (n = 29). The 117 studies could be assigned to five categories “teaching methods (n = 53)”, “teaching quality (n = 33)”, “performance evaluation and examination formats (n=19)”, “students’ views (n = 8)” and “patients’ and standardized patients’ views (n=4)”.ConclusionsThe present work shows a wide spectrum of teaching and research activities and a certain level of evidence for the effectiveness of individual teaching methods. It can be used as orientation and impulse generator for the further development of medical education in the field of PE.

Der feste Patientenstamm als potentielle Fallgrube prospektiver Studien im primärärztlichen SektorThe Stable Patient Collective as a Potential Pitfall of Prospective Primary Health-Care Studies. A Qualitative Inquiry among General Practitioners

ZusammenfassungHintergrund und Ziel:Die Transparent- und Bekanntmachung von Studienproblemen können die Planung und Durchführung von Hausarztstudien enorm bereichern. Unter Einbeziehung der Studienteilnehmer ist es möglich, etwaige Studienproblempunkte genauer zu eruieren. Ziel der vorliegenden qualitativen Untersuchung war es deshalb, anhand einer Nachbefragung der beteiligten Hausärzte die Ursachen unerwarteter Studienergebnisse einer longitudinalen Interventionsstudie mit zwei Erhebungszeitpunkten herauszufinden. Zu beiden Zeitpunkten jener Studie wurden jeweils 2 400 Patienten einer Screeninguntersuchung zu alkoholbezogenen Gesundheitsstörungen unterzogen.Methodik:Es wurden retrospektiv Telefoninterviews mit 39 der insgesamt 43 an obiger Studie beteiligten Hausärzte durchgeführt. Die Auswertung erfolgte inhaltsanalytisch nach der Qualitativen Inhaltsanalyse von Philipp Mayring.Ergebnisse:Die Hausärzte erwähnten aus der Literatur bekannte Problempunkte als Ursachen für die unerwarteten Ergebnisse: der hohe Dokumentationsaufwand, das tabuisierte Studienthema und die Motivationsminderung zum Studienende. Eine weitere Ursache wurde aufgegriffen: der wiederholte Rekrutierungsablauf dieser Interventionsstudie. Es herrschte Unklarheit darüber, ob Patienten vom ersten Erhebungszeitpunkt auch beim zweiten eingeschlossen werden durften. Zudem scheint der sich wenig verändernde Patientenstamm in der Hausarztpraxis ein Hauptgrund gewesen zu sein; demnach konnten zum zweiten Erhebungszeitpunkt der Studie nur wenige neue Patienten eingeschlossen werden.Schlussfolgerung:Für die Planung von Studien mit wiederholten Durchläufen sowie chronischen und tabuisierten Erkrankungen muss die spezielle Situation in der Hausarztpraxis mit bekanntem und festem Patientenstamm, der sich sogar innerhalb von Jahren nur wenig ändert, berücksichtigt werden. Die hier erörterten Ursachen für Rekrutierungsprobleme von Patienten können wichtig sein, um selektionsbedingte Fehler bei hausärztlichen Studien zu vermeiden.AbstractBackground and Purpose:Transparency and disclosure of problems in primary health-care studies can add enormous information to the planning and conduction of such studies. By means of the inquiry of study participants, important data on study problems can be found out. Therefore, the aim of this qualitative study was to identify the causes of unexpected results of an intervention study in general practitioners’ (GPs) practices by means of an inquiry of the participating GPs. The very study was about diagnosing alcohol- related health disorders at two points of time 1 year apart each with 2,400 primary health-care patients.Methods:39 of the 43 participating GPs of the study mentioned were asked by telephone about the possible causes of the unexpected study results. Data analysis was conducted according to the Qualitative Content Analysis of Philipp Mayring.Results:The GPs mentioned problems that are already described in the international literature: the high expenses for study documentation, tabooed health topics, and declining participation motivation at the end of the study. A further cause of the unexpected study results was picked up: the repeated patient recruitment of this intervention study. It was unclear for the GPs whether they could include the same patients at the first and second recruitment point of time. Moreover, one main reason for the unexpected study results seems to be the stable patient collective of GPs’ practices; according to that, only few new patients could be included at the second time point of recruitment.Conclusion:In primary health-care research requiring several time points for patient recruitment, one has to consider potential tabooed health topics and the special situation in primary health-care practices. This situation is characterized by a stable amount of known patients, even over years. The here-discussed causes of recruitment problems might be essential to avoid selection bias in primary health-care studies.

Der feste Patientenstamm als potentielle Fallgrube prospektiver Studien im primärärztlichen Sektor@@@The Stable Patient Collective as a Potential Pitfall of Prospective Primary Health-Care Studies. A Qualitative Inquiry among General Practitioners: Eine qualitative Erhebung unter Studienhausärzten

ZusammenfassungHintergrund und Ziel:Die Transparent- und Bekanntmachung von Studienproblemen können die Planung und Durchführung von Hausarztstudien enorm bereichern. Unter Einbeziehung der Studienteilnehmer ist es möglich, etwaige Studienproblempunkte genauer zu eruieren. Ziel der vorliegenden qualitativen Untersuchung war es deshalb, anhand einer Nachbefragung der beteiligten Hausärzte die Ursachen unerwarteter Studienergebnisse einer longitudinalen Interventionsstudie mit zwei Erhebungszeitpunkten herauszufinden. Zu beiden Zeitpunkten jener Studie wurden jeweils 2 400 Patienten einer Screeninguntersuchung zu alkoholbezogenen Gesundheitsstörungen unterzogen.Methodik:Es wurden retrospektiv Telefoninterviews mit 39 der insgesamt 43 an obiger Studie beteiligten Hausärzte durchgeführt. Die Auswertung erfolgte inhaltsanalytisch nach der Qualitativen Inhaltsanalyse von Philipp Mayring.Ergebnisse:Die Hausärzte erwähnten aus der Literatur bekannte Problempunkte als Ursachen für die unerwarteten Ergebnisse: der hohe Dokumentationsaufwand, das tabuisierte Studienthema und die Motivationsminderung zum Studienende. Eine weitere Ursache wurde aufgegriffen: der wiederholte Rekrutierungsablauf dieser Interventionsstudie. Es herrschte Unklarheit darüber, ob Patienten vom ersten Erhebungszeitpunkt auch beim zweiten eingeschlossen werden durften. Zudem scheint der sich wenig verändernde Patientenstamm in der Hausarztpraxis ein Hauptgrund gewesen zu sein; demnach konnten zum zweiten Erhebungszeitpunkt der Studie nur wenige neue Patienten eingeschlossen werden.Schlussfolgerung:Für die Planung von Studien mit wiederholten Durchläufen sowie chronischen und tabuisierten Erkrankungen muss die spezielle Situation in der Hausarztpraxis mit bekanntem und festem Patientenstamm, der sich sogar innerhalb von Jahren nur wenig ändert, berücksichtigt werden. Die hier erörterten Ursachen für Rekrutierungsprobleme von Patienten können wichtig sein, um selektionsbedingte Fehler bei hausärztlichen Studien zu vermeiden.AbstractBackground and Purpose:Transparency and disclosure of problems in primary health-care studies can add enormous information to the planning and conduction of such studies. By means of the inquiry of study participants, important data on study problems can be found out. Therefore, the aim of this qualitative study was to identify the causes of unexpected results of an intervention study in general practitioners’ (GPs) practices by means of an inquiry of the participating GPs. The very study was about diagnosing alcohol- related health disorders at two points of time 1 year apart each with 2,400 primary health-care patients.Methods:39 of the 43 participating GPs of the study mentioned were asked by telephone about the possible causes of the unexpected study results. Data analysis was conducted according to the Qualitative Content Analysis of Philipp Mayring.Results:The GPs mentioned problems that are already described in the international literature: the high expenses for study documentation, tabooed health topics, and declining participation motivation at the end of the study. A further cause of the unexpected study results was picked up: the repeated patient recruitment of this intervention study. It was unclear for the GPs whether they could include the same patients at the first and second recruitment point of time. Moreover, one main reason for the unexpected study results seems to be the stable patient collective of GPs’ practices; according to that, only few new patients could be included at the second time point of recruitment.Conclusion:In primary health-care research requiring several time points for patient recruitment, one has to consider potential tabooed health topics and the special situation in primary health-care practices. This situation is characterized by a stable amount of known patients, even over years. The here-discussed causes of recruitment problems might be essential to avoid selection bias in primary health-care studies.