The laboratory approach to the diagnosis of autoimmune diseases: is it time to change?

Array technology and proteomics are about to launch the era of multiplexed analysis, which allows simultaneous detection of numerous autoantibody specificities and the possibility of defining broad autoantibody profiles. This will probably improve disease staging, risk stratification, prognosis and treatment. However, although these technologies are very promising, they are still in their infancy, and therefore need to undergo strict analytical and clinical validation processes. The latter should involve clinicians and pathologists in prospective, multicentric studies conducted on large numbers of patients to define the specific significance of the various autoantibody profiles. Establishing common standards for the publication and sharing of microarray-generated data will be important for this purpose. Only when these studies have been completed will these new technologies find a place in clinical laboratories. Although we are entering a decade which will probably see a radical change in the diagnostic approach to autoimmune diseases, we do not yet have sufficient knowledge to apply proteomic technologies on a large scale. For the time being, therefore, it is advisable to continue using well-established approaches and diagnostic algorithms such as those reported in the international guidelines, which have been prepared in accordance with the principles of appropriateness and evidence-based medicine.     

The German medical dissertation--time to change?

German medical students must conduct a research project and write a dissertation in order to receive the title "Doctor." However, the dissertation is not required to graduate, enter a residency, or practice medicine. About 90% of practicing physicians hold the title "Doctor"; a career in academic medicine almost always requires it. Although no convincing evidence supports the usefulness of the dissertation, many regard its completion as important to maintaining a high level of scientific competence and patient care. In recent years, the number of successfully completed dissertations has declined. Lack of time during medical school, the perceived irrelevance of the dissertation to medical practice, and the poor design of many projects may be at least part of the problem. There is also increasing evidence that conducting research frequently delays graduation and may affect clinical skills because students working on projects attend fewer classes, ward rounds, and clinical tutorials and do not spent sufficient time preparing for examinations. The scientific value of students' research has also been criticized; critics point out that students do not have enough time or experience to critically analyze methods and data, and they often are not properly supervised. European unification will probably lead to standardized requirements for medical education and research. The authors hope this will eliminate the dissertation requirement in Germany.     

The quality of evidence in health informatics: how did the quality of healthcare IT evaluation publications develop from 1982 to 2005?

OBJECTIVE: To obtain an overview of study designs and study methods used in research evaluating IT in health care, to present a list of quality criteria by which all kinds of reported evaluation studies on IT systems in health care can be assessed, and to assess the quality of reported evaluation studies on IT in health care and its development over time (1982-2005). METHODS: A generic 10-item list of quality indicators was developed based on existing literature on quality of medical and medical informatics publications. It is applicable to all kind of IT evaluation papers and not restricted to randomized controlled trials. One hundred and twenty explanatory papers evaluating the effects of an IT system in health care published between 1982 and 2005 were randomly selected from PubMed, the study designs and study methods were extracted, and the quality indicators were used to assess the quality of each paper by two independent raters. RESULTS: The inter-rater variability of scoring the 10 quality indicators as assessed by a pre-test with nine papers was good (K=0.87). There was a trend towards more multi-centre studies and authors coming more frequently from various departments. About 70% of the studies used a design other than a randomized controlled trial (RCT). Forty percent of the studies combined at least two different data acquisition methods. The quality of IT evaluation papers, as defined by the quality indicators, was only slightly improving in time (Spearman correlation coefficient [rs]=0.19). The quality of RCTs publications was significantly higher than the quality of non-RCT studies (p<0.001). CONCLUSION: The continuous and dominant number of non-RCT studies reflects the various approaches applicable to evaluate IT systems in health care. Despite the increasing discussion on evidence-based health informatics, the quality of published evaluation studies on IT interventions in health care is still insufficient in some aspects. Journal editors and referees should take care that reports of evaluation on IT systems contain all aspects needed for a sufficient understanding and reproducibility of a paper. Publication guidelines should be developed to support more complete and better publications of IT evaluation papers.     

How did the ancestral HIV-1 group M retrovirus get to Leopoldville from southeastern Cameroon?

In previous papers in this journal, I have described and elaborated a hypothesis for the origin and evolution of a strain of HIV that has produced a lethal pandemic. Here I address the provocative question of how the ancestral HIV-1 group M retrovirus got to Leopoldville (Kinshasa, where the pandemic clearly spawned) from southeastern Cameroon (where the HIV-1 strains all seemed to originate from transfer of SIV(cpz) to humans). Consistent with the phylogenetic history of HIV-1 group M (e.g., by Korber et al.), I place the critical relocation of the ancestral HIV-1 in the timeframe 1920-1927. However, unlike other hypotheses, I believe that the ancestral retrovirus was already well adapted to humans and can be identified as HIV-1 Group M subtype A(pre)-1927. Based on documents from that time period (1920-1928), it can be shown that it was not unusual for native Africans to be brought as far as 500 miles for treatment at the Leopoldville clinic (national borders were no issue because health agencies had mandate to work throughout Cameroon and Congo-Brazzaville). Specifically, sleeping sickness (trypanosomiasis) was one of the diseases of most concern at the Leopoldville clinic; in the period 1926-1928 there was an outbreak of sleeping sickness in Cameroon; and one of the native African children in the pamaquine (plasmoquineTM) study that I believe selected for the major HIV-1 group M subgroups had trypanosomiasis. Thus, this child (or other patients/relatives from Cameroon) could have brought the ancestral HIV-1 group M retrovirus to the Leopoldville laboratory and spread it among the group of children who were undergoing treatment for malaria between February and August 1927. The diagnosis and monitoring of these protozoan diseases (trypanosomiasis and malaria) involved repetitive sampling of blood, which provides many opportunities for spreading the ancestral HIV-1 infection.     

The “Truman Show” delusion: Psychosis in the global village

Introduction. We report a novel delusion, primarily persecutory in form, in which the patient believes that he is being filmed, and that the films are being broadcast for the entertainment of others.

Methods. We describe a series of patients who presented with a delusional system according to which they were the subjects of something akin to a reality television show that was broadcasting their daily life for the entertainment of others. We then address three questions, the first concerning how to characterise the delusion, the second concerning the role of culture in delusion, and the third concerning the implications of cultural studies of delusion for the cognitive theory of delusion.

Results. Delusions are both variable and stable: Particular delusional ideas are sensitive to culture, but the broad categories of delusion are stable both across time and culture. This stability has implications for the form a cognitive theory of delusion can take.

Conclusions. Cultural studies of delusion have important contributions to make to the cognitive theory of delusion.     

The not-for-profit form and translational research: Kerr revisited?

Translational research conducted in academic health centers is confounded by the organizational structure in which the work is performed. Investigators must obtain research funding and appropriate recognition as a part of a research team in a not-for-profit environment which has more readily rewarded basic work, and individual accomplishments. What results is a unique form of conflict of interest, best understood by relating the basic principles underlying the not-for-profit form to the conduct of translational research in the AHC setting.     

Can variables from the transtheoretical model predict dietary change?

The present study was designed to see whether variables from the transtheoretical model could account for changes in behavior, as opposed to changes of stage. A broadly representative sample (N = 356) completed measures of transtheoretical model constructs and dietary intake at baseline; dietary intake was measured at follow-up. One of the processes of change, self-reevaluation, predicted changes in behavior and significantly mediated the effect of past behavior on future behavior. It is rare that social cognitive variables mediate the effects of past behavior on future behavior meaning that self-reevaluation provides a potential avenue for promoting dietary change.     

Bridging the transmission gap: An end to an important mystery of attachment research?

Abstract

The authors provide a context for this special section by arguing that the attachment relationships of infancy fulfil an evolutionary role in ensuring that the brain structures that come to subserve social cognition are appropriately organised and prepared to equip the individual for the collaborative existence with other people for which his or her brain was designed. Processes as fundamental as gene expression or changes in receptor densities can be seen as direct functions of the extent of understanding of mental states provided by the caregiving environment. If the attachment relationship is indeed a major organiser of brain development, it is even more important to understand the processes that underpin the transgenerational transmission of attachment patterns. The contributions of the papers in the special section to understanding the role of reflective function in the development of attachment and social cognition are reviewed, and the implications for the development of both theory and practice are explored.     

Bridging the transmission gap: an end to an important mystery of attachment research?

The authors provide a context for this special section by arguing that the attachment relationships of infancy fulfil an evolutionary role in ensuring that the brain structures that come to subserve social cognition are appropriately organised and prepared to equip the individual for the collaborative existence with other people for which his or her brain was designed. Processes as fundamental as gene expression or changes in receptor densities can be seen as direct functions of the extent of understanding of mental states provided by the caregiving environment. If the attachment relationship is indeed a major organiser of brain development, it is even more important to understand the processes that underpin the transgenerational transmission of attachment patterns. The contributions of the papers in the special section to understanding the role of reflective function in the development of attachment and social cognition are reviewed, and the implications for the development of both theory and practice are explored.     

Was isolation of Veillonella from spinal osteomyelitis possible due to poor tissue perfusion?

From a needle biopsy of the body of the 12th thoracic vertebra in a 74-year-old man with spinal osteomyelitis a Veillonella parvula was isolated. The significance of this bacterium as lactic acid indicator has been considered and discussed. Since this strictly anaerobic bacterium mainly uses lactic acid for energy generation, lactic acid must continuously and sufficiently have been produced in or near to the vertebrate body to permit outgrowth of this bacterium. Since neither microbial infections nor tumours could be demonstrated, we finally hypothesised that in this patient poor tissue perfusion has been the primary cause of lactic acid production.     

Cytopathology: Why did it take so long to thrive?

Lionel S. Beale of London made some of the earliest contributions to Cytopathology in the 1850–1860s. Cytopathology then experienced a 60+ year hiatus during which few advances were made. In 1927, Londoner Leonard S. Dudgeon published his wet film method for rapid intraoperative diagnosis and in 1928 Greek‐American George Papanicolaou and Romanian Aurel A. Babe? independently discovered that cervical cancer can be diagnosed using vaginal smears; these were huge advancements. Yet, there was another hiatus where little progress was made which lasted until the publications of Papanicolaou and Trout in the early 1940s. After that, the field of exfoliative Cytopathology immediately flourished. None of the standard histories of Cytopathology explain these two gaps. Primary and secondary historical sources were examined to explain this pattern. The author concludes that the first hiatus is explained by the 19th Century pathology establishment's strong opposition to the doctrine of the uniqueness of cancer cells that was being pushed by only a few maverick pathologists; in fact, for many mainstream pathologists, cancer was rigidly defined by cell behavior (metastases and invasion) and not cell morphology well into the 20th Century. Biopsy‐based diagnosis faced similar opposition but advanced more rapidly as it was possible to examine increased numbers of cells in a pattern that partially maintained their normal adjacencies and architecture. The second hiatus is explained by economic pressures supporting intraoperative frozen section diagnoses and, in the instance of vaginal smears, the embryonic state of the public campaign supporting the importance of early cancer diagnosis. Diagn. Cytopathol. 2015;43:257–263. © 2015 Wiley Periodicals, Inc.