Low rate of rhesus immunization from rh- incompatible blood transfusions during liver and heart transplant surgery

Transfusion of one unit or more of Rh-positive red blood cells normally causes circulating anti-D antibody to appear 2-6 months later in 80-95% of Rh persons. We asked whether transplant immunosuppression with cyclosporine and corticosteroids affects Rh immuniza¬tion. Nineteen Rh" liver, heart, and heart-lung transplant recipients received 3—153 (median: 10) units of Rh+ RBCs at surgery and were tested for anti-D >2 months later. Three patients developed anti-D at 11—15 days; one may have had an unusually rapid primary immune response and two were secondary to previous exposure by pregnancy. None of the other 16 patients had anti-D when tested 2.5-51 months later (13 patients, >11.5 months). This low rate of Rhesus immunization in association with cyclosporine immunosuppression allows greater flexibility in meeting the transfusion needs of Rh- liver and heart transplant patients. Caution is still advised in young females and in patients who may have been previously exposed to Rh+ RBCs by transfusion or by pregnancy prior to the availability of perinatal Rh immune globulin twenty years ago. Other humoral immune responses to some vaccines or infectious agents may also be impaired in transplant patients© 1989 by The Williams and Wilkins Co

Stoicism, the physician, and care of medical outliers

BACKGROUND: Medical outliers present a medical, psychological, social, and economic challenge to the physicians who care for them. The determinism of Stoic thought is explored as an intellectual basis for the pursuit of a correct mental attitude that will provide aid and comfort to physicians who care for medical outliers, thus fostering continued physician engagement in their care. DISCUSSION: The Stoic topics of good, the preferable, the morally indifferent, living consistently, and appropriate actions are reviewed. Furthermore, Zeno's cardinal virtues of Justice, Temperance, Bravery, and Wisdom are addressed, as are the Stoic passions of fear, lust, mental pain, and mental pleasure. These concepts must be understood by physicians if they are to comprehend and accept the Stoic view as it relates to having the proper attitude when caring for those with long-term and/or costly illnesses. SUMMARY: Practicing physicians, especially those that are hospital based, and most assuredly those practicing critical care medicine, will be emotionally challenged by the medical outlier. A Stoic approach to such a social and psychological burden may be of benefit

Rationale, design and conduct of a randomised controlled trial evaluating a primary care-based complex intervention to improve the quality of life of heart failure patients: HICMan (Heidelberg Integrated Case Management) : study protocol

Background: Chronic congestive heart failure (CHF) is a complex disease with rising prevalence, compromised quality of life (QoL), unplanned hospital admissions, high mortality and therefore high burden of illness. The delivery of care for these patients has been criticized and new strategies addressing crucial domains of care have been shown to be effective on patients' health outcomes, although these trials were conducted in secondary care or in highly organised Health Maintenance Organisations. It remains unclear whether a comprehensive primary care-based case management for the treating general practitioner (GP) can improve patients' QoL. Methods/Design: HICMan is a randomised controlled trial with patients as the unit of randomisation. Aim is to evaluate a structured, standardized and comprehensive complex intervention for patients with CHF in a 12-months follow-up trial. Patients from intervention group receive specific patient leaflets and documentation booklets as well as regular monitoring and screening by a prior trained practice nurse, who gives feedback to the GP upon urgency. Monitoring and screening address aspects of disease-specific selfmanagement, (non)pharmacological adherence and psychosomatic and geriatric comorbidity. GPs are invited to provide a tailored structured counselling 4 times during the trial and receive an additional feedback on pharmacotherapy relevant to prognosis (data of baseline documentation). Patients from control group receive usual care by their GPs, who were introduced to guidelineoriented management and a tailored health counselling concept. Main outcome measurement for patients' QoL is the scale physical functioning of the SF-36 health questionnaire in a 12-month follow-up. Secondary outcomes are the disease specific QoL measured by the Kansas City Cardiomyopathy questionnaire (KCCQ), depression and anxiety disorders (PHQ-9, GAD-7), adherence (EHFScBS and SANA), quality of care measured by an adapted version of the Patient Chronic Illness Assessment of Care questionnaire (PACIC) and NTproBNP. In addition, comprehensive clinical data are collected about health status, comorbidity, medication and health care utilisation. Discussion: As the targeted patient group is mostly cared for and treated by GPs, a comprehensive primary care-based guideline implementation including somatic, psychosomatic and organisational aspects of the delivery of care (HICMAn) is a promising intervention applying proven strategies for optimal care. Trial registration: Current Controlled Trials ISRCTN30822978

Principled Selection of Baseline Covariates to Account for Censoring in Randomized Trials with a Survival Endpoint

The analysis of randomized trials with time-to-event endpoints is nearly always plagued by the problem of censoring. As the censoring mechanism is usually unknown, analyses typically employ the assumption of non-informative censoring. While this assumption usually becomes more plausible as more baseline covariates are being adjusted for, such adjustment also raises concerns. Pre-specification of which covariates will be adjusted for (and how) is difficult, thus prompting the use of data-driven variable selection procedures, which may impede valid inferences to be drawn. The adjustment for covariates moreover adds concerns about model misspecification, and the fact that each change in adjustment set, also changes the censoring assumption and the treatment effect estimand. In this paper, we discuss these concerns and propose a simple variable selection strategy that aims to produce a valid test of the null in large samples. The proposal can be implemented using off-the-shelf software for (penalized) Cox regression, and is empirically found to work well in simulation studies and real data analyses

Einflussfaktoren auf Gründungsdispositionen und Entrepreneurship-Merkmalen von Studierenden – Ein Vergleich von Russland und Deutschland

Dieser Beitrag geht mit dem internationalen Forschungsprojekt „Gründungen und Entrepreneurship bei Studierenden“ (GESt-Studie) einher, das zum Ziel hat, Gründungsneigungen und Entrepreneurship-Merkmale von Studierenden aus verschiedenen Ländern zielgruppendifferenziert zu analysieren, um daraus bedarfsorientierte Handlungsempfehlungen für eine adäquate Konzeptionierung von Gründungsausbildung und Gründungsförderung abzuleiten. Die Ergebnisse dieses Ländervergleiches veranschaulichen, dass die befragten Studierenden in Russland ein höheres Gründungsinteresse repräsentieren und sich insgesamt deutlich stärker mit Entrepreneurship beschäftigen als die in Deutschland befragten Studierenden. Allerdings basiert diese in Russland positivere Ausgangsbasis für eine Gründungsrealisierung stärker auf der Gründungsmotivation aus ökonomischer Notwendigkeit, die oftmals nicht auf innovativen Geschäftsideen beruht, heraus. Insgesamt betrachtet sind sowohl den Studierenden in Deutschland, von denen sich etwa jeder Zweite noch gar nicht mit der Gründungsthematik auseinandergesetzt hat, als auch den Studierenden in Russland, die stärker durch fehlende unternehmerische Qualifikationen von der Gründung abgehalten werden, insbesondere gründungsspezifische Grundkenntnisse und unternehmerische Fähigkeiten zu vermitteln, was fächerübergreifend und während des gesamten Studiums zu erfolgen hat.

A distinct metabolic signature predicts development of fasting plasma glucose

ABSTRACT: BACKGROUND: High blood glucose and diabetes are amongst the conditions causing the greatest losses in years of healthy life worldwide. Therefore, numerous studies aim to identify reliable risk markers for development of impaired glucose metabolism and type 2 diabetes. However, the molecular basis of impaired glucose metabolism is so far insufficiently understood. The development of so called `omics' approaches in the recent years promises to identify molecular markers and to further understand the molecular basis of impaired glucose metabolism and type 2 diabetes. Although univariate statistical approaches are often applied, we demonstrate here that the application of multivariate statistical approaches is highly recommended to fully capture the complexity of data gained using high-throughput methods. METHODS: We took blood plasma samples from 172 subjects who participated in the prospective Metabolic Syndrome Berlin Potsdam follow-up study (MESY-BEPO Follow-up). We analysed these samples using Gas Chromatography coupled with Mass Spectrometry (GC-MS), and measured 286 metabolites. Furthermore, fasting glucose levels were measured using standard methods at baseline, and after an average of six years. We did correlation analysis and built linear regression models as well as Random Forest regression models to identify metabolites that predict the development of fasting glucose in our cohort. RESULTS: We found a metabolic pattern consisting of nine metabolites that predicted fasting glucose development with an accuracy of 0.47 in tenfold cross-validation using Random Forest regression. We also showed that adding established risk markers did not improve the model accuracy. However, external validation is eventually desirable. Although not all metabolites belonging to the final pattern are identified yet, the pattern directs attention to amino acid metabolism, energy metabolism and redox homeostasis. CONCLUSIONS: We demonstrate that metabolites identified using a high-throughput method (GC-MS) perform well in predicting the development of fasting plasma glucose over several years. Notably, not single, but a complex pattern of metabolites propels the prediction and therefore reflects the complexity of the underlying molecular mechanisms. This result could only be captured by application of multivariate statistical approaches. Therefore, we highly recommend the usage of statistical methods that seize the complexity of the information given by high-throughput methods

Isoforms of Retinol binding protein 4 (RBP4) are increased in chronic diseases of the kidney but not of the liver

<p>Abstract</p> <p>Background</p> <p>The levels of retinol-binding protein 4 (RBP4) – the carrier protein for Vitamin A in plasma – are tightly regulated under healthy circumstances. The kidney, the main site of RBP4 catabolism, contributes to an elevation of RBP4 levels during chronic kidney disease (CKD) whereas during chronic liver disease (CLD) RBP4 levels decrease. Little is known about RBP4 isoforms including apo-RBP4, holo-RBP4 as well as RBP4 truncated at the C-terminus (RBP4-L and RBP4-LL) except that RBP4 isoforms have been reported to be increased in hemodialysis patients. Since it is not known whether CLD influence RBP4 isoforms, we investigated RBP4 levels, apo- and holo-RBP4 as well as RBP4-L and RBP4-LL in plasma of 36 patients suffering from CKD, in 55 CLD patients and in 50 control subjects. RBP4 was determined by ELISA and apo- and holo-RBP4 by native polyacrylamide gel electrophoresis (PAGE). RBP4-L and RBP4-LL were analyzed after immunoprecipitation by mass spectrometry (MALDI-TOF-MS).</p> <p>Results</p> <p>RBP4 isoforms and levels were highly increased in CKD patients compared to controls (P < 0.05) whereas in CLD patients RBP4 isoforms were not different from controls. In addition, in hepatic dysfunction RBP4 levels were decreased whereas the amount of isoforms was not affected.</p> <p>Conclusion</p> <p>The occurrence of RBP4 isoforms is not influenced by liver function but seems to be strongly related to kidney function and may therefore be important in investigating kidney function and related disorders.</p

Development of genomic resources for the prairie vole (Microtus ochrogaster): construction of a BAC library and vole-mouse comparative cytogenetic map

<p>Abstract</p> <p>Background</p> <p>The prairie vole (<it>Microtus ochrogaster</it>) is a premier animal model for understanding the genetic and neurological basis of social behaviors. Unlike other biomedical models, prairie voles display a rich repertoire of social behaviors including the formation of long-term pair bonds and biparental care. However, due to a lack of genomic resources for this species, studies have been limited to a handful of candidate genes. To provide a substrate for future development of genomic resources for this unique model organism, we report the construction and characterization of a bacterial artificial chromosome (BAC) library from a single male prairie vole and a prairie vole-mouse (<it>Mus musculus</it>) comparative cytogenetic map.</p> <p>Results</p> <p>We constructed a prairie vole BAC library (CHORI-232) consisting of 194,267 recombinant clones with an average insert size of 139 kb. Hybridization-based screening of the gridded library at 19 loci established that the library has an average depth of coverage of ~10×. To obtain a small-scale sampling of the prairie vole genome, we generated 3884 BAC end-sequences totaling ~2.8 Mb. One-third of these BAC-end sequences could be mapped to unique locations in the mouse genome, thereby anchoring 1003 prairie vole BAC clones to an orthologous position in the mouse genome. Fluorescence in situ hybridization (FISH) mapping of 62 prairie vole clones with BAC-end sequences mapping to orthologous positions in the mouse genome was used to develop a first-generation genome-wide prairie vole-mouse comparative cytogenetic map. While conserved synteny was observed between this pair of rodent genomes, rearrangements between the prairie vole and mouse genomes were detected, including a minimum of five inversions and 16 inter-chromosomal rearrangements.</p> <p>Conclusions</p> <p>The construction of the prairie vole BAC library and the vole-mouse comparative cytogenetic map represent the first genome-wide modern genomic resources developed for this species. The BAC library will support future genomic, genetic and molecular characterization of this genome and species, and the isolation of clones of high interest to the vole research community will allow for immediate characterization of the regulatory and coding sequences of genes known to play important roles in social behaviors. In addition, these resources provide an excellent platform for future higher resolution cytogenetic mapping and full genome sequencing.</p

Nursing brain drain from India

In response to recent findings regarding migration of health workers out of Africa, we provide data from a survey of Indian nurses suggesting that up to one fifth of the nursing labour force may be lost to wealthier countries through circular migration