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1.  Expression of CD11b (MAC-1) and CD162 (PSGL-1) on monocytes is decreased under conditions of deep hypothermic circulatory arrest 
Deep hypothermic circulatory arrest (DHCA) is a common technique used to protect vital organs during surgical interventions on the thoracic aorta or during surgery for complex congenital heart disease. Activated leukocytes are key mediators of inflammatory responses during ischemia. Intercellular crosstalk between leukocytes, platelets and endothelial cells is mediated by cell adhesion molecules. These molecules trigger complex cell-cell interaction mechanisms and initiate the release of proinflammatory molecules. One parameter that is known to have a significant impact on inflammatory cell activation and the production of proinflammatory markers is temperature. However, to the best of our knowledge, no data have yet been published on the effect of hypothermia on leukocyte surface markers during DHCA. Thus, the aim of the present study was to investigate the effect of hypothermia on the expression of cell adhesion molecules on monocytes under DHCA conditions in vitro. Blood samples collected from 11 healthy volunteers were incubated in a well-established model simulating circulatory arrest at 36°C and 18°C for 30 min. The expression of cluster of differentiation (CD) molecule 11B (CD11b), CD54 and CD162 on monocytes was measured as the mean fluorescence intensity (MFI) using flow cytometry. The expression level of CD11b on monocytes was significantly decreased following the incubation of the blood samples at 18°C compared with the level in blood samples incubated at 36°C (P<0.001). After 30 min of blood stasis in the circulatory arrest model, the expression level of CD162 on monocytes was significantly lower in the blood samples incubated at 18°C than in those incubated at 36°C (P<0.001). No association was identified between temperature and the surface expression of CD54 on monocytes following 30 min of stasis. These findings demonstrate that deep hypothermia decreases the expression of CD11b and CD162 on monocytes in an experimental setup simulating the conditions of DHCA. This may be the result of the inhibition of leukocyte-endothelial and leukocyte-platelet interactions, which may be a beneficial aspect of deep hypothermia that affects the inflammatory response and tissue damage during DHCA.
doi:10.3892/etm.2014.1737
PMCID: PMC4079448
CD11b; CD162; CD54; deep hypothermic circulatory arrest; leukocytes
2.  Colorectal cancer stage at diagnosis in migrants versus non-migrants (KoMigra): study protocol of a cross-sectional study in Germany 
BMC Cancer  2014;14:123.
Background
In Germany, about 20% of the total population have a migration background. Differences exist between migrants and non-migrants in terms of health care access and utilisation. Colorectal cancer is the second most common malignant tumour in Germany, and incidence, staging and survival chances depend, amongst other things, on ethnicity and lifestyle. The current study investigates whether stage at diagnosis differs between migrants and non-migrants with colorectal cancer in an area of high migration and attempts to identify factors that can explain any differences.
Methods/Design
Data on tumour and migration status will be collected for 1,200 consecutive patients that have received a new, histologically verified diagnosis of colorectal cancer in a high migration area in Germany in the previous three months. The recruitment process is expected to take 16 months and will include gastroenterological private practices and certified centres for intestinal diseases. Descriptive and analytical analysis will be performed: the distribution of variables for migrants versus non-migrants and participants versus non-participants will be analysed using appropriate χ2-, t-, F- or Wilcoxon tests. Multivariable, logistic regression models will be performed, with the dependent variable being the dichotomized stage of the tumour (UICC stage I versus more advanced than UICC stage I). Odds ratios and associated 95%-confidence intervals will be calculated. Furthermore, ordered logistic regression models will be estimated, with the exact stage of the tumour at diagnosis as the dependent variable. Predictors used in the ordered logistic regression will be patient characteristics that are specific to migrants as well as patient characteristics that are not. Interaction models will be estimated in order to investigate whether the effects of patient characteristics on stage of tumour at the time of the initial diagnosis is different in migrants, compared to non-migrants.
Discussion
An association of migration status or other socioeconomic variables with stage at diagnosis of colorectal cancer would be an important finding with respect to equal health care access among migrants. It would point to access barriers or different symptom appraisal and, in the long term, could contribute to the development of new health care concepts for migrants.
Trial registration
German Clinical Trials Register DRKS00005056.
doi:10.1186/1471-2407-14-123
PMCID: PMC3939398  PMID: 24559172
Colorectal cancer; Cross-sectional; Observational study; Ethnicity; Hard-to-reach population; Health care access; Migrants
3.  How to improve drug dosing for patients with renal impairment in primary care - a cluster-randomized controlled trial 
BMC Family Practice  2012;13:91.
Background
Patients with chronic kidney disease (CKD) are at increased risk for inappropriate or potentially harmful prescribing. The aim of this study was to examine whether a multifaceted intervention including the use of a software programme for the estimation of creatinine clearance and recommendation of individual dosage requirements may improve correct dosage adjustment of relevant medications for patients with CKD in primary care.
Methods
A cluster-randomized controlled trial was conducted between January and December 2007 in small primary care practices in Germany. Practices were randomly allocated to intervention or control groups. In each practice, we included patients with known CKD and elderly patients (≥70 years) suffering from hypertension. The practices in the intervention group received interactive training and were provided a software programme to assist with individual dose adjustment. The control group performed usual care. Data were collected at baseline and at 6 months. The outcome measures, analyzed across individual patients, included prescriptions exceeding recommended maximum daily doses, with the primary outcome being prescriptions exceeding recommended standard daily doses by more than 30%.
Results
Data from 44 general practitioners and 404 patients are included. The intervention was effective in reducing prescriptions exceeding the maximum daily dose per patients, with a trend in reducing prescriptions exceeding the standard daily dose by more than 30%.
Conclusions
A multifaceted intervention including the use of a software program effectively reduced inappropriately high doses of renally excreted medications in patients with CKD in the setting of small primary care practices.
Trial registration
Current Controlled Trials ISRCTN02900734
doi:10.1186/1471-2296-13-91
PMCID: PMC3515431  PMID: 22953792
4.  Primary care practice-based care management for chronically ill patients (PraCMan): study protocol for a cluster randomized controlled trial [ISRCTN56104508] 
Trials  2011;12:163.
Background
Care management programmes are an effective approach to care for high risk patients with complex care needs resulting from multiple co-occurring medical and non-medical conditions. These patients are likely to be hospitalized for a potentially "avoidable" cause. Nurse-led care management programmes for high risk elderly patients showed promising results. Care management programmes based on health care assistants (HCAs) targeting adult patients with a high risk of hospitalisation may be an innovative approach to deliver cost-efficient intensified care to patients most in need.
Methods/Design
PraCMan is a cluster randomized controlled trial with primary care practices as unit of randomisation. The study evaluates a complex primary care practice-based care management of patients at high risk for future hospitalizations. Eligible patients either suffer from type 2 diabetes mellitus, chronic obstructive pulmonary disease, chronic heart failure or any combination. Patients with a high likelihood of hospitalization within the following 12 months (based on insurance data) will be included in the trial.
During 12 months of intervention patients of the care management group receive comprehensive assessment of medical and non-medical needs and resources as well as regular structured monitoring of symptoms. Assessment and monitoring will be performed by trained HCAs from the participating practices. Additionally, patients will receive written information, symptom diaries, action plans and a medication plan to improve self-management capabilities. This intervention is addition to usual care.
Patients from the control group receive usual care.
Primary outcome is the number of all-cause hospitalizations at 12 months follow-up, assessed by insurance claims data. Secondary outcomes are health-related quality of life (SF12, EQ5D), quality of chronic illness care (PACIC), health care utilisation and costs, medication adherence (MARS), depression status and severity (PHQ-9), self-management capabilities and clinical parameters. Data collection will be performed at baseline, 12 and 24 months (12 months post-intervention).
Discussion
Practice-based care management for high risk individuals involving trained HCAs appears to be a promising approach to face the needs of an aging population with increasing care demands.
Trial registration
Current Controlled Trials ISRCTN56104508
doi:10.1186/1745-6215-12-163
PMCID: PMC3141533  PMID: 21714883
5.  Development of a primary care-based complex care management intervention for chronically ill patients at high risk for hospitalization: a study protocol 
Background
Complex care management is seen as an approach to face the challenges of an ageing society with increasing numbers of patients with complex care needs. The Medical Research Council in the United Kingdom has proposed a framework for the development and evaluation of complex interventions that will be used to develop and evaluate a primary care-based complex care management program for chronically ill patients at high risk for future hospitalization in Germany.
Methods and design
We present a multi-method procedure to develop a complex care management program to implement interventions aimed at reducing potentially avoidable hospitalizations for primary care patients with type 2 diabetes mellitus, chronic obstructive pulmonary disease, or chronic heart failure and a high likelihood of hospitalization. The procedure will start with reflection about underlying precipitating factors of hospitalizations and how they may be targeted by the planned intervention (pre-clinical phase). An intervention model will then be developed (phase I) based on theory, literature, and exploratory studies (phase II). Exploratory studies are planned that entail the recruitment of 200 patients from 10 general practices. Eligible patients will be identified using two ways of 'case finding': software based predictive modelling and physicians' proposal of patients based on clinical experience. The resulting subpopulations will be compared regarding healthcare utilization, care needs and resources using insurance claims data, a patient survey, and chart review. Qualitative studies with healthcare professionals and patients will be undertaken to identify potential barriers and enablers for optimal performance of the complex care management program.
Discussion
This multi-method procedure will support the development of a primary care-based care management program enabling the implementation of interventions that will potentially reduce avoidable hospitalizations.
doi:10.1186/1748-5908-5-70
PMCID: PMC2949784  PMID: 20858242
6.  Cardiovascular magnetic resonance of myocardial infarction after blunt chest trauma: a heartbreaking soccer-shot 
Cardiac injury occasionally occurs as a result of blunt chest trauma. Most cardiac complications in chest trauma are due to myocardial contusion rather than direct damage to the coronary arteries. However, traumatic coronary injury has been reported, and a variety of underlying pathophysiological mechanisms have been proposed. We present a 26 year old patient presenting with an acute coronary syndrome as a consequence of a soccer-shot impact to the chest. CMR showed apical inferior infarction, as well as multiple small septal lesions which were presumed to have resulted from embolization. The culprit lesion was a proximal 75% LAD stenosis with a prominent plaque-rupture and thrombus-formation, and the distal LAD was occluded by thromboembolic material.
doi:10.1186/1532-429X-11-39
PMCID: PMC2770538  PMID: 19818151
7.  The Systematic Guideline Review: Method, rationale, and test on chronic heart failure 
Background
Evidence-based guidelines have the potential to improve healthcare. However, their de-novo-development requires substantial resources – especially for complex conditions, and adaptation may be biased by contextually influenced recommendations in source guidelines. In this paper we describe a new approach to guideline development – the systematic guideline review method (SGR), and its application in the development of an evidence-based guideline for family physicians on chronic heart failure (CHF).
Methods
A systematic search for guidelines was carried out. Evidence-based guidelines on CHF management in adults in ambulatory care published in English or German between the years 2000 and 2004 were included. Guidelines on acute or right heart failure were excluded. Eligibility was assessed by two reviewers, methodological quality of selected guidelines was appraised using the AGREE instrument, and a framework of relevant clinical questions for diagnostics and treatment was derived. Data were extracted into evidence tables, systematically compared by means of a consistency analysis and synthesized in a preliminary draft. Most relevant primary sources were re-assessed to verify the cited evidence. Evidence and recommendations were summarized in a draft guideline.
Results
Of 16 included guidelines five were of good quality. A total of 35 recommendations were systematically compared: 25/35 were consistent, 9/35 inconsistent, and 1/35 un-rateable (derived from a single guideline). Of the 25 consistencies, 14 were based on consensus, seven on evidence and four differed in grading. Major inconsistencies were found in 3/9 of the inconsistent recommendations. We re-evaluated the evidence for 17 recommendations (evidence-based, differing evidence levels and minor inconsistencies) – the majority was congruent. Incongruity was found where the stated evidence could not be verified in the cited primary sources, or where the evaluation in the source guidelines focused on treatment benefits and underestimated the risks. The draft guideline was completed in 8.5 man-months. The main limitation to this study was the lack of a second reviewer.
Conclusion
The systematic guideline review including framework development, consistency analysis and validation is an effective, valid, and resource saving-approach to the development of evidence-based guidelines.
doi:10.1186/1472-6963-9-74
PMCID: PMC2698839  PMID: 19426504
8.  Health-related quality of life among general practice patients with differing chronic diseases in Germany: Cross sectional survey 
BMC Public Health  2008;8:246.
Background
This study was carried out to compare the HRQoL of patients in general practice with differing chronic diseases with the HRQoL of patients without chronic conditions, to evaluate the HRQoL of general practice patients in Germany compared with the HRQoL of the general population, and to explore the influence of different chronic diseases on patients' HRQoL, independently of the effects of multiple confounding variables.
Methods
A cross-sectional questionnaire survey including the SF-36, the EQ-5D and demographic questions was conducted in 20 general practices in Germany. 1009 consecutive patients aged 15–89 participated. The SF-36 scale scores of general practice patients with differing chronic diseases were compared with those of patients without chronic conditions. Differences in the SF-36 scale/summary scores and proportions in the EQ-5D dimensions between patients and the general population were analyzed. Independent effects of chronic conditions and demographic variables on the HRQoL were analyzed using multivariable linear regression and polynomial regression models.
Results
The HRQoL for general practice patients with differing chronic diseases tended to show more physical than mental health impairments compared with the reference group of patients without. Patients in general practice in Germany had considerably lower SF-36 scores than the general population (P < 0.001 for all) and showed significantly higher proportions of problems in all EQ-5D dimensions except for the self-care dimension (P < 0.001 for all). The mean EQ VAS for general practice patients was lower than that for the general population (69.2 versus 77.4, P < 0.001). The HRQoL for general practice patients in Germany seemed to be more strongly affected by diseases like depression, back pain, OA of the knee, and cancer than by hypertension and diabetes.
Conclusion
General practice patients with differing chronic diseases in Germany had impaired quality of life, especially in terms of physical health. The independent impacts on the HRQoL were different depending on the type of chronic disease. Findings from this study might help health professionals to concern more influential diseases in primary care from the patient's perspective.
doi:10.1186/1471-2458-8-246
PMCID: PMC2515099  PMID: 18638419
9.  Unimolecular Reactions of Dihydrated Alkaline Earth Metal Dications M2+(H2O)2, M = Be, Mg, Ca, Sr, and Ba: Salt-Bridge Mechanism in the Proton-Transfer Reaction M2+(H2O)2 → MOH+ + H3O+ 
The unimolecular reactivity of M2+(H2O)2, M = Be, Mg, Ca, Sr, and Ba, is investigated by density functional theory. Dissociation of the complex occurs either by proton transfer to form singly charged metal hydroxide, MOH+, and protonated water, H3O+, or by loss of water to form M2+(H2O) and H2O. Charge transfer from water to the metal forming H2O+ and M+(H2O) is not favorable for any of the metal complexes. The relative energetics of these processes are dominated by the metal dication size. Formation of MOH+ proceeds first by one water ligand moving to the second solvation shell followed by proton transfer to this second-shell water molecule and subsequent Coulomb explosion. These hydroxide formation reactions are exothermic with activation energies that are comparable to the water binding energy for the larger metals. This results in a competition between proton transfer and loss of a water molecule. The arrangement with one water ligand in the second solvation shell is a local minimum on the potential energy surface for all metals except Be. The two transition states separating this intermediate from the reactant and the products are identified. The second transition state determines the height of the activation barrier and corresponds to a M2+–OH−–H3O+ “salt-bridge” structure. The computed B3LYP energy of this structure can be quantitatively reproduced by a simple ionic model in which Lewis charges are localized on individual atoms. This salt-bridge arrangement lowers the activation energy of the proton-transfer reaction by providing a loophole on the potential energy surface for the escape of H3O+. Similar salt-bridge mechanisms may be involved in a number of proton-transfer reactions in small solvated metal ion complexes, as well as in other ionic reactions.
doi:10.1021/ja982653+
PMCID: PMC1409760  PMID: 16554906
10.  Case management for the treatment of patients with major depression in general practices – rationale, design and conduct of a cluster randomized controlled trial – PRoMPT (Primary care Monitoring for depressive Patient's Trial) [ISRCTN66386086] – Study protocol 
BMC Public Health  2005;5:101.
Background
Depression is a disorder with high prevalence in primary health care and a significant burden of illness. The delivery of health care for depression, as well as other chronic illnesses, has been criticized for several reasons and new strategies to address the needs of these illnesses have been advocated. Case management is a patient-centered approach which has shown efficacy in the treatment of depression in highly organized Health Maintenance Organization (HMO) settings and which might also be effective in other, less structured settings.
Methods/Design
PRoMPT (PRimary care Monitoring for depressive Patients Trial) is a cluster randomised controlled trial with General Practice (GP) as the unit of randomisation. The aim of the study is to evaluate a GP applied case-management for patients with major depressive disorder. 70 GPs were randomised either to intervention group or to control group with the control group delivering usual care. Each GP will include 10 patients suffering from major depressive disorder according to the DSM-IV criteria. The intervention group will receive treatment based on standardized guidelines and monthly telephone monitoring from a trained practice nurse. The nurse investigates the patient's status concerning the MDD criteria, his adherence to GPs prescriptions, possible side effects of medication, and treatment goal attainment. The control group receives usual care – including recommended guidelines. Main outcome measure is the cumulative score of the section depressive disorders (PHQ-9) from the German version of the Prime MD Patient Health Questionnaire (PHQ-D). Secondary outcome measures are the Beck-Depression-Inventory, self-reported adherence (adapted from Moriskey) and the SF-36. In addition, data are collected about patients' satisfaction (EUROPEP-tool), medication, health care utilization, comorbidity, suicide attempts and days out of work.
The study comprises three assessment times: baseline (T0) , follow-up after 6 months (T1) and follow-up after 12 months (T2).
Discussion
Depression is now recognized as a disorder with a high prevalence in primary care but with insufficient treatment response. Case management seems to be a promising intervention which has the potential to bridge the gap of the usually time-limited and fragmented provision of care. Case management has been proven to be effective in several studies but its application in the private general medical practice setting remains unclear.
doi:10.1186/1471-2458-5-101
PMCID: PMC1262729  PMID: 16207375
11.  Gas-Phase Reactions of Cationic Vanadium-Phosphorus Oxide Clusters with C2Hx (x=4, 6): A DFT-Based Analysis of Reactivity Patterns 
The reactivities of the adamantane-like heteronuclear vanadium-phosphorus oxygen cluster ions [VxP4−xO10].+ (x=0, 2–4) towards hydrocarbons strongly depend on the V/P ratio of the clusters. Possible mechanisms for the gas-phase reactions of these heteronuclear cations with ethene and ethane have been elucidated by means of DFT-based calculations; homolytic C–H bond activation constitutes the initial step, and for all systems the P–O. unit of the clusters serves as the reactive site. More complex oxidation processes, such as oxygen-atom transfer to, or oxidative dehydrogenation of the hydrocarbons require the presence of a vanadium atom to provide the electronic prerequisites which are necessary to bring about the 2e− reduction of the cationic clusters.
doi:10.1002/chem.201203050
PMCID: PMC3743165  PMID: 23322620
C–H activation; cluster compounds; density functional calculations; gas-phase reactions; reaction mechanisms

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