[Qualitative Research in Health Services Research - Discussion Paper, Part 3: Quality of Qualitative Research]. / Qualitative Studien in der Versorgungsforschung - Diskussionspapier, Teil 3: Qualität qualitativer Studien.

The third and final discussion paper of the German Network of Health Services Research's (DNVF) "Qualitative Methods Working Group" demonstrates methods for the evaluation and quality of qualitative research in health services research. In this paper we discuss approaches described in evaluating qualitative studies, including: an orientation to the general principles of empirical research, an approach-specific course of action, as well as procedures based on the research-process and criteria-oriented approaches. Divided into general and specific aspects to be considered in a qualitative study quality evaluation, the central focus of the discussion paper undertakes an extensive examination of the process and criteria-oriented approaches. The general aspects include the participation of relevant groups in the research process as well as ethical aspects of the research and data protection issues. The more specific aspects in evaluating the quality of qualitative research include considerations about the research interest, research questions, and the selection of data collection methods and types of analyses. The formulated questions are intended to guide reviewers and researchers to evaluate and to develop qualitative research projects appropriately. The intention of this discussion paper is to ensure a transparent research culture, and to reflect on and discuss the methodological and research approach of qualitative studies in health services research. With this paper we aim to initiate a discussion on high quality evaluation of qualitative health services research.

[The Preventive Home Visit as a Preventive Intervention to Reach the Elderly--Effectiveness and Cost-Effectiveness of Different Ways of Approach]. / Der präventive Hausbesuch als zugehende Präventionsmaßnahme im Alter--Effektivität und Kosteneffektivität von Zugangswegen.

The aim of the study was a systematical further development of targeted approaches. Research questions were how elderly women and men could be motivated to participate in a preventive intervention and by which approaches elderly with different health risks could be reached. In several stages a specific motivational material was developed. Afterwards two different approaches to the elderly (general practice, health insurance) were tested and evaluated considering its (cost) effectiveness.

[Qualitative research in health services research - discussion paper, Part 1: What is the idea?]. / Qualitative Studien in der Versorgungsforschung - Diskussionspapier, Teil 1: Gegenstandsbestimmung.

In this first part of a 3-part discussion paper the working group "Qualitative Methods" in the German Network of Health Services Research (DNVF) identifies the potentials and opportunities qualitative research methods provide for health services research. Many research questions relevant for health services research require the use of qualitative methods. However, the potential of and need for qualitative research in health services research has not yet received sufficient attention from funding bodies. We discuss the applicability and importance of qualitative research for the field of health services research. We then move on to describe the key characteristics of qualitative research that need to be taken into account in health services research. We discuss characteristics such as open-ended (qualitative) data, interpretation of meanings, the search for contradictions, closeness to everyday life, openness towards change or modification of the research question and processes in the context of health services research. To ensure a high-quality approach in qualitative methods for the health services research, sufficient competency in methods and appropriate settings that account for the peculiarities of qualitative methods need to be developed. These include an appropriate time frame and sufficient and qualified personnel to conduct qualitative research. Qualitative research is not a research paradigm in itself rather it comprises of many different and diverging approaches. The goal of this paper is to show the diversity of qualitative research methods, its importance for health services research, and to open up the discussion on strategies for integrating qualitative methods into health services research.

[Qualitative research in health services research - discussion paper, Part 2: Qualitative research in health services research in Germany - an overview]. / Qualitative Studien in der Versorgungsforschung - Diskus-sionspapier, Teil 2: Stand qualitativer Versorgungsforschung in Deutschland - ein exemplarischer Überblick.

BACKGROUND: This is the second part of a 3-part discussion paper by the working group on "Qualitative Methods" in the German network of health services research (DNVF) that shall contribute to the development of a memorandum concerning qualitative health services research. It aims to depict the different types of qualitative research that are conducted in health services research in Germany. In addition, the authors present a specific set of qualitative data collection and analysis tools to demonstrate the potential of qualitative research for health services research. QUALITATIVE RESEARCH IN HEALTH SERVICES RESEARCH - AN OVERVIEW: To give an overview of the types of qualitative research conducted in German health services research, the abstracts of the 8th German Conference on Health Services Research were filtered to identify qualitative or mixed-methods studies. These were then analysed by looking at the context which was studied, who was studied, the aims of the studies, and what type of methods were used. Those methods that were mentioned most often for data collection and analysis are described in detail. QUALITATIVE RESEARCH AT THE CONFERENCE FOR HEALTH SERVICES RESEARCH 2009: Approximately a fifth of all abstracts (n=74) had a qualitative (n=47) or a mixed-methods approach combining quantitative and qualitative methods (n=27). Research aims included needs assessment (41%), survey development (36%), evaluation (22%), and theorizing (1%). Data collection mostly consisted of one-on-one interviews (n=45) and group discussions (n=29). Qualitative content analysis was named in 35 abstracts, 30 abstracts did not reference their method of analysis. In addition to a quantitative summary of the abstract findings, the diversity of fields addressed by qualitative methods is highlighted. CONCLUSION: Although drawing conclusions on the use of qualitative methods in German health services research from the analysis of conference abstracts is not possible, the overview we present demonstrates the diversity of methods used for data collection and analysis and showed that a few select methods are extensively used. One of the tasks a memorandum of qualitative health services research should accomplish is to highlight underutilized research methods, which may help to develop the potential of qualitative methodology in German health services research.

[Prediction models on return to work of rehabilitants following vocational training programme participation]. / Prognosemodelle zur beruflichen Wiedereingliederung von Rehabilitanden nach beruflichen Bildungsmassnahmen.

PURPOSE: Vocational rehabilitation aims at vocational reintegration of disabled persons. Three different types of rehabilitative vocational training programmes - i. e., vocational retraining in Berufsförderungswerken (vocational rehabilitation centres), in-plant vocational retraining according to the German dual system of initial vocational training, and vocational continuation courses - were explored concerning subsequent vocational reintegration of the participants. METHODS: The rehabilitants were given standardized questionnaires at the beginning (T1) and 1 year after their vocational training (T5). Between 61% and 64% of those rehabilitants who had completed their vocational training took part in the final postal survey 1 year after the vocational rehabilitation (T5). Data of the T1-questionnaires were used for prediction models concerning successful vocational reintegration of the rehabilitants one year after their vocational training. RESULTS: Important differences were found between the participants of the three rehabilitation programmes in socio-demographic, health-related and psychological characteristics, due to specific statutory criteria for assignment of disabled persons to the different forms of vocational rehabilitation. 1 year after the vocational training, 55% of the rehabilitants of both forms of vocational retraining (external, in-plant) and 31% of the participants of vocational continuation courses were employed in the first labour market. For all 3 forms of vocational rehabilitation programmes, 3 significant predictors were found concerning successful vocational reintegration of the rehabilitants: the local job market at the participants' residence, specific health complaints (pain or sleep disturbances) and social support. Other significant predictors were a number of psychological, sociological, and occupation-related biographical variables. DISCUSSION: A set of variables proved to be relevant predictors for vocational reintegration of rehabilitants 1 year after the end of vocational retraining and continuation measures. Some of these variables could be used practically for specific interventions to increase chances of vocational reintegration for participants of vocational rehabilitation measures.

Inhibition by ethanol of excitatory amino acid receptors and nicotinic acetylcholine receptors at rat locus coeruleus neurons.

The frequency of spontaneous action potentials of locus coeruleus (LC) neurons was recorded extracellularly in pontine slices of the rat brain. Ethanol (1-100 mM) elevated the firing rate in most neurons; this effect was concentration-dependent. (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; 0.03-1 microM), kainate (0.1-3 microM), N-methyl-D-aspartate (NMDA; 1-30 microM), substance P (0.01-1 microM), nicotine (0.1-10 microM) and alpha,beta-methylene ATP (alpha,beta-meATP; 0.3-30 microM), all increased the firing. Application of ethanol (10-100 mM) to the superfusion medium for 10 min, reproducibly and concentration-dependently inhibited the facilitatory effect of NMDA (10 microM). However, the inhibitory effect of ethanol (100 mM) decreased during a 30-min superfusion period and after the wash-out of ethanol the sensitivity of LC neurons to NMDA (10 microM) tended to overshoot above their initial level. Although NMDA was more potent in the absence than in the presence of external Mg2+, ethanol (100 mM) continued to depress the facilitatory effect of a low concentration of NMDA (3 microM) in a Mg(2+)-free medium. By contrast, in a medium containing normal Mg2+, ethanol (100 mM) failed to significantly interfere with the increase in firing rate induced by a high concentration of NMDA (30 microM). The effects of kainate (0.5 microM), AMPA (0.3 microM) and nicotine (1 microM) were also depressed by ethanol (100 mM), while the effects of substance P (0.03 microM) and alpha,beta-meATP (30 microM) were not changed.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential inhibitory action of cationic amino acids on protein synthesis in pancreatic rat islets.

The effect of cationic amino acids, i.e. L-arginine and L-lysine, on protein synthesis in isolated rat islets of Langerhans has been investigated. Except for prosomatostatin, the formation of islet proteins is strongly depressed by these amino acids. This effect can be demonstrated within a few minutes and is rapidly reversible. For proglucagon, efficient concentrations of arginine are in the range of 1 to 10 mmol/l. The sensitivity of proinsulin formation to arginine is glucose-dependent: at 2.5 mmol/l, inhibitory concentrations of arginine are 10-fold lower than in the case of proglucagon. High glucose (20 mmol/l) almost completely protects proinsulin synthesis from this inhibition. The proteolytic conversion steps in hormonal precursor processing are not influenced by cationic amino acids as studied in intact islets and in a cell-free translational system. It is concluded that arginine and lysine inhibit protein synthesis in islet cells at the translational level. The release of these amino acids by prohormone conversion may exert a feed-back control on proinsulin formation that is modulated by glucose.

Early O-glycosidic glycosylation of proglucagon in pancreatic islets: an unusual type of prohormonal modification.

Proglucagon from rat islets is identified as a glycoprotein by its binding to soybean lectin and by the biosynthetic incorporation of [14C]galactosamine. Glycosylation can be demonstrated for both forms of proglucagon, i.e. the primary translation product which is detectable as early as 30 s after incubation of isolated islets with radioactive amino acids (proglucagon a), and its conversion product of slightly higher electrophoretic mobility which is formed after 5-10 min of incubation (proglucagon b). This glycosylation is determined to be of the O-glycosidic type by the following criteria: rat proglucagon has previously been shown to lack an acceptor sequence for N-glycosidic linkage of sugars, the sugar bond in rat proglucagon is labile under mild alkaline conditions, glycosylated serine is demonstrated in proteolytic lysates of both the early and the late form of this prohormone. O-glycosidic linkage of sugars has not been reported for other prohormones. Its early formation and the apparent absence of N-glycosidically bound sugars in proglucagon give evidence for an unusual type of protein glycosylation.

Conversion of proglucagon in pancreatic alpha cells: the major endproducts are glucagon and a single peptide, the major proglucagon fragment, that contains two glucagon-like sequences.

It has previously been shown by biosynthetic labeling studies that glucagon is synthesized in mammalian islets via an 18-kDa precursor, proglucagon, that during processing gives rise to glucagon and a secreted peptide of 10 kDa (the major proglucagon fragment, MPGF). We have now developed a simple procedure for the isolation of this peptide from rat pancreatic islets and have characterized it more fully. On the basis of its amino acid composition, MPGF is identified as the COOH-terminal portion of proglucagon that contains two glucagon-related sequences. These sequences do not appear to be liberated from MPGF in alpha cells of the islets of Langerhans but MPGF may be processed further elsewhere in the body or in other cells of the gastrointestinal tract that produce glucagon precursors.

Formation of biologically active peptides.

Many small biologicaly active peptides are derived from larger precursor forms which fulfil a variety of roles in the synthesis, segregation and intracellular migration of secretory products. Limited proteolysis may occur at several stages during this process, giving rise to products that are either degraded (e.g. the prepeptides) or discharged coordinately from their cells of origin during exocytosis (e.g. insulin and C-peptide). Molecular defects have recently been found to occur at cleavage sites in proinsulin as well as in other proproteins, and these point mutations may, in some instances, be responsible for familial metabolic disorders. The nature and cell specificity of the proteolytic enzymes involved in the conversion of the various precursor forms remains unresolved. Recent studies in our laboratory have led to the identification of precursors of glucagon and somatostatin in rat islets of Langerhans. Analysis of tryptic maps of these precursors has shown that a trypsin-like enzyme would be sufficient to cleave the C-terminally located somatostatin sequence from its precursor (relative molecular mass 12,500), but that both trypsin-like and carboxypeptidase B-like enzymes would be necessary to cleave the internal glucagon sequence from its prohormone (relative molecular mass 18,000). Molecular cloning techniques have provided valuable new approaches to analysing the structures of a variety of precursor forms, including those for insulin, gastrin, growth hormone, adrenocorticotropic hormone and the endorphins, and in the future will undoubtedly shed more light on the structures of their chromosomal genes, the mechanisms regulating their expression, and their evolutionary origins.

Identification of prosomatostatin in pancreatic islets.

A 12.5-kilodalton protein not related to insulin or glucagon was detected in pulse-chase-labeled rat islets of Langerhans. Although this protein reacted poorly with various somatostatin antisera, analysis of two-dimensional peptide maps showed that it contains all of the tryptic fragments of somatostatin, which is located at its COOH terminus. Proteolytic conversion of the putative prosomatostatin, which took place parallel to the processing of proinsulin and proglucagon in pulse-chase experiments, coincided with the appearance of newly synthesized somatostatin and proceeded without the apparent involvement of major intermediate forms.

Identification and processing of proglucagon in pancreatic islets.

Immunoprecipitation and tryptic peptide analysis of newly synthesized proteins from rat islets have identified an 18,000 molecular weight (MW) protein as proglucagon. Conversion of this precursor was kinetically similar to the conversion of proinsulin and resulted in the formation of both pancreatic glucagon and a 10,000-MW protein lacking this hormonal sequence.

Detection and kinetic behavior of preproinsulin in pancreatic islets.

Newly synthesized rat islet proteins have been analyzed by polyacrylamide slab gel electrophoresis and fluorography. A minor component having an apparent molecular weight of 11,100 was identified as preproinsulin by the sensitivity of its synthesis to glucose, the pattern of NH2-terminal leucine residues, and the rapidity of its appearance and disappearance during incubation of islets or islet cell tumors. A small amount of labeled peptide material which may represent the excised NH2-terminal extension of preproinsulin or its fragment was also detected. The kinetics of formation and processing of the preproinsulin fraction were complex, consisting of a rapidly turning over component having a half-life of about 1 min and a slower minor fraction that may have bypassed the normal cleavage process. The electrophoretic resolution of the preproinsulin and proinsulin fractions into two bands each is consistent with the presence of two closely related gene products in rat islets rather than intermediate stages in the processing of these peptides.

Inhibitory effect of colchicine on amylase secretion by rat parotid glands. Possible localization in the Golgi area.

Colchicine inhibited amylase secretion by isolated rat parotid glands only 6 h after administration of the drug in vivo. This delayed effect was not the result of the inability of the drug to reach its reaction site. When parotid glands were emptied of their secretory granules by isoproterenol treatment, the subsequent replenishment of cells with granules was inhibited by colchicines. Colchicine concomitantly produced alterations of the Golgi complexes, the cisternae of which were reduced in size and surrounded by clusters of microvesicles. Incubation of parotid glands with colchicines for prolonged durations failed to alter stored amylase secretion as stimulated by isoproterenol, but it inhibited the release of de novo synthesized enzyme. Another colchicines-binding activity, firmly bound to the particular fraction of homogenates, was found, of which a part may represent membrane located microtubular protein. An assembly-disassembly cycle of microtubules appears to exist in the parotid gland, as in the liver. However, only 14 percent of tubulin was found to be polymerized as microtubules in parotid glands as opposed to 40 percent in the liver. The present data suggest that colchicine primarily inhibits the transfer of secretory material towards or away from the Golgi complexes but not the hormone-stimulated secretion of stored amylase.