Beyond image defined risk factors (IDRFs): a delphi survey highlighting definition of the surgical complexity index (SCI) in neuroblastoma.

PURPOSE: Preoperative evaluation of Image Defined Risk Factors (IDRFs) in neuroblastoma (NB) is crucial for determining suitability for upfront resection or tumor biopsy. IDRFs do not all carry the same weighting in predicting tumor complexity and surgical risk. In this study we aimed to assess and categorize a surgical complexity (Surgical Complexity Index, SCI) in NB resection. METHODS: A panel of 15 surgeons was involved in an electronic Delphi consensus survey to identify and score a set of shared items predictive and/or indicative of surgical complexity, including the number of preoperative IDRFs. A shared agreement included the achievement of at least 75% consensus focused on a single or two close risk categories. RESULTS: After 3 Delphi rounds, agreement was established on 25/27 items (92.6%). A severity score was established for each item ranging from 0 to 3 with an overall SCI range varying from a minimum score of zero to a maximum score of 29 points for any given patient. CONCLUSIONS: A consensus on a SCI to stratify the risks related to neuroblastoma tumor resection was established by the panel experts. This index will now be deployed to critically assign a better severity score to IDRFs involved in NB surgery.

Selective use of Peptide Receptor Radionuclide Therapy following comparative imaging of Ga-68 DOTATATE PET/CT against I-131 MIBG scintigraphy in a small Asian cohort of Adult Neuroblastoma.

Adult neuroblastoma (AN) is rare with an extremely poor prognosis. No standard therapy exists for this entity and treatment options are limited in recurrent or refractory disease. 131I-MIBG has been used in combination with myeloablative therapy before autologous bone marrow transplantation or in a salvage therapy setting. However, myelotoxicity is a dose-limiting factor in heavily pre-treated patients and response is not always sustained. Somatostatin receptor scintigraphy and theranostics with radiolabelled somatostatin receptor analogues are becoming more commonplace with the recognition of these receptors in over 90% of neuroblastoma cells. We describe three AN patients assessed for somatostatin receptor status and the novel use of 177Lu-based peptide recep-tor radionuclide therapy (PRRT) in two of them and a literature review.

Electric Single-Molecule Hybridization Detector for Short DNA Fragments.

By combining DNA nanotechnology and high-bandwidth single-molecule detection in nanopipets, we demonstrate an electric, label-free hybridization sensor for short DNA sequences (<100 nucleotides). Such short fragments are known to occur as circulating cell-free DNA in various bodily fluids, such as blood plasma and saliva, and have been identified as disease markers for cancer and infectious diseases. To this end, we use as a model system an 88-mer target from the RV1910c gene in Mycobacterium tuberculosis, which is associated with antibiotic (isoniazid) resistance in TB. Upon binding to short probes attached to long carrier DNA, we show that resistive-pulse sensing in nanopipets is capable of identifying rather subtle structural differences, such as the hybridization state of the probes, in a statistically robust manner. With significant potential toward multiplexing and high-throughput analysis, our study points toward a new, single-molecule DNA-assay technology that is fast, easy to use, and compatible with point-of-care environments.

Feasibility of a real-time hand hygiene notification machine learning system in outpatient clinics.

BACKGROUND: Various technologies have been developed to improve hand hygiene (HH) compliance in inpatient settings; however, little is known about the feasibility of machine learning technology for this purpose in outpatient clinics. AIM: To assess the effectiveness, user experiences, and costs of implementing a real-time HH notification machine learning system in outpatient clinics. METHODS: In our mixed methods study, a multi-disciplinary team co-created an infrared guided sensor system to automatically notify clinicians to perform HH just before first patient contact. Notification technology effects were measured by comparing HH compliance at baseline (without notifications) with real-time auditory notifications that continued till HH was performed (intervention I) or notifications lasting 15 s (intervention II). User experiences were collected during daily briefings and semi-structured interviews. Costs of implementation of the system were calculated and compared to the current observational auditing programme. FINDINGS: Average baseline HH performance before first patient contact was 53.8%. With real-time auditory notifications that continued till HH was performed, overall HH performance increased to 100% (P < 0.001). With auditory notifications of a maximum duration of 15 s, HH performance was 80.4% (P < 0.001). Users emphasized the relevance of real-time notification and contributed to technical feasibility improvements that were implemented in the prototype. Annual running costs for the machine learning system were estimated to be 46% lower than the observational auditing programme. CONCLUSION: Machine learning technology that enables real-time HH notification provides a promising cost-effective approach to both improving and monitoring HH, and deserves further development in outpatient settings.

[What do medical students think of family medicine? Results of an online cross-sectional study in the federal state of Baden-Wuerttemberg]. / Wie sehen Medizinstudierende die Allgemeinmedizin? Ergebnisse einer onlinebasierten Querschnittstudie in Baden-Württemberg.

BACKGROUND: In the context of physician shortages, critical factors influencing career choice need to be better understood. The aim of this study was to explore experiences students have had with family medicine in order to develop additional strategies for recruiting family medicine trainees. METHODS: Students from the five medical faculties in the federal state of Baden-Wuerttemberg were invited to participate in an online-survey via email. A purpose-built questionnaire was used. In addition to descriptive statistics, analysis included linear partial correlations controlled for age, gender, and semester, which were calculated between the variable "I believe family medicine is an attractive job" and the 31 variables of the survey. Linear regression was used to analyze the influence of experiences with family medicine and statements about family medicine to the perception of family medicine as an attractive specialty. RESULTS: 1299 students participated in the survey. About half of the participants (49.7 %) considered working as a primary care physician to be attractive or partly attractive. 49.6 % of students reported positive experiences with family medicine as a patient and 33.1 % as a family member. 24.3 % reported positive experiences during the compulsory 1-2 weeks general practice internship and 18.1 % during a four weeks elective placement. For 302 participants (23.3 %), family medicine is presented positively in the media. 178 (13.7 %) consider family medicine to have high importance in both undergraduate and postgraduate education. Positive influences on judging attractiveness of family medicine were: own experience with family medicine as a clinical elective (rpart= + 0.450), own experience with family medicine as a patient (rpart= + 0.218), perception that family medicine offers a diversified working day (rpart= + 0.259), and perception that family medicine offers a good salary (rpart= + 0.242). CONCLUSION: To enable students during undergraduate studies to have practical experience with family medicine seems to be an important influence on judging family medicine attractive.

[Development, factor-analytical control and psychometric evaluation of a questionnaire on specialty choices among medical students]. / Entwicklung, faktorenanalytische Überprüfung und psychometrische Evaluierung eines Fragebogens zur Gebietswahl von Medizinstudierenden.

AIM OF THE STUDY: A questionnaire was developed and validated which assesses factors influencing career choices of medical students and their perception of possibilities in general practice. METHODS: The first questionnaire version, which was developed based on a systematic literature review, was checked for comprehensibility and redundancy using concurrent think aloud. The revised version was filled out by a pilot sample of medical students and the factor structure was assessed using principal component analysis (PCA). The final version was filled out in an online survey by medical students of all 5 Medical Faculties in the federal state of Baden-Wuerttemberg. The factor structure was validated with a confirmatory factor analysis (CFA). Reliability was assessed as internal consistency using Cronbach's α. RESULTS: The questionnaire comprises 2 parts: ratings of (A) the individual importance and of (B) the possibilities in general practice on 5-point scales. The first version comprising 118 items was shortened to 63 items after conducting interviews using concurrent think aloud. A further 3 items giving no information were removed after piloting the questionnaire on 179 students. The 27 items of part A were structured in 7 factors (PCA): image, personal ambition, patient orientation, work-life balance, future perspectives, job-related ambition, and variety in job. This structure had a critical fit in the CFA applied to the final version filled out by 1 299 students. Internal consistency of the factors was satisfactory to very good (Cronbach's α=0.55-0.81). CONCLUSION: The questionnaire showed good psychometric properties. Further, not assessed factors influence career choice resulting in unexplained variance in our dataset and the critical fit of the model.

Swelling in the upper arm: the presentation and management of an isolated brachial artery aneurysm.

True aneurysms of the brachial artery are uncommon. We describe the presentation and surgical management of an isolated, brachial artery aneurysm in a 64-year-old woman. Excision of the aneurysm and long saphenous venous interposition grafting was performed with no postoperative complications and histology demonstrated true aneurysmal degeneration.

Multiple indomethacin-induced colonic perforations in an adolescent.

Colonic perforation is an uncommon cause of acute abdomen in paediatric patients, and can present a diagnostic enigma as well as management challenge to the paediatric surgeon. An adolescent developed multiple colonic perforations following a short course of oral indomethacin, requiring emergency hemicolectomy. This is the youngest known case of enteral non-steroidal anti-inflammatory drug (NSAID)-mediated large bowel injury. We review current evidence on NSAID-related enteropathy, and postulate potentiating mechanisms that may have accounted for the unusually rapid clinical course of our patient.

[Aspirations of medical students: "planning for a secure career" - results of an online-survey among students at five medical schools in Germany]. / Berufswunsch "planungssicherer Arbeitsplatz" - Ergebnisse einer Online-Befragung unter Medizinstudierenden.

BACKGROUND: In times of shortage of doctors, expectations and interests of the future generation of doctors towards their career aspiration is of major importance. The aim of this study was to analyze expectations of medical students at the five medical schools in the State of Baden-Wuerttemberg (Germany) concerning their career choice and factors influencing it. METHODS: Between January and February 2010, 1299 medical students (out of 12 062 medical students at the five medical schools) participated in an online-survey. In addition to sociodemographic items, career choice and aspects of planning reliability were raised. RESULTS: Three quarters of the students assign a medical profession for their future occupation. There is a dominance of internal medicine (n = 152), gynaecology (n = 127), paediatrics (n = 125), surgery (n = 115), anaesthesiology (n = 101), and family medicine (n = 88). The time point of decision varies between the different undergraduate years of medical school and specialty. Students at the beginning of their studies seem to be interested mostly in surgery. During medical school the interests towards internal medicine grows. Regarding planning dependability important aspects for medical students were to work in a job that has a future (61.2 % fully agree), to have a safe job (57.7 %), and to have a safe income (57.1 %). Less important seems to be to have good opportunity to earn money (29.6 %). CONCLUSIONS: Interest in a certain specialty changes markedly at during medical school. Factors such as economical guarantee, good future prospects and also the studies itself have an essential impact for students on choosing a specific career. Strategies to face physicians' shortage in different specialties need to be close to the needs and expectations of future physicians. This is not only valid for the undergraduate time period but also for the work circumstances of their future.

Delayed diagnosis of pseudoaneurysm formation in a patient with diaphyseal aclasis.

A 15 year old boy, with known diaphyseal aclasis, presented with a swollen left leg. The diagnosis of popliteal pseudoaneurysm, a known and well understood vascular complication, was delayed due to presentation suggestive of a chondrosarcoma. In this age group, sarcomatous change is more common and a potentially sinister complication of diaphyseal aclasis. Following a sarcoma MDT referral, the correct diagnosis was confirmed by ultrasound and CT angiogram. This case identifies one of the largest, non-ruptured popliteal pseudoaneurysms reported and illustrates an unusual complication of a rare orthopaedic genetic condition, which is potentially limb threatening.

Contribution of functional variation in the IL13 gene to allergy, hay fever and asthma in the NSHD longitudinal 1946 birth cohort.

BACKGROUND: Genetic variants of the two adjacent genes, IL13 and IL4 have frequently been reported as being associated with susceptibility to atopy and asthma, both in adults and children, and some studies also suggest association with lung function and chronic obstructive pulmonary disease. METHODS: In this study, we examined for the first time the effect of these variants in 2918 adults in a longitudinal birth cohort, the British National Survey of Health and Development, where there are extensive life style, developmental and environmental data. We examine two IL13 single nucleotide polymorphisms (SNPs) IL13 rs20541 (R110Q) and rs1800925 (-1024C>T) and one IL4 SNP, rs2070874 (-33C>T) with likely function. RESULTS: We show that IL13 rs20541 and rs1800925 are each significantly associated with self-reported asthma and allergy, and that this association is not confounded by any of the known developmental and environmental risk factors for asthma and atopy, including in particular place of birth. IL13 rs20541 does however act as a confounder for the IL13 rs1800925 associations, meaning that there is no statistical support for rs1800925 having an independent effect. There is nevertheless evidence for interaction between smoking and rs1800925, with allergy as outcome. None of the SNPs showed association with measures of lung function, nor any interaction with the effect of smoking on lung function. CONCLUSION: In a longitudinal population cohort we have established a role for polymorphism of IL13 in determining susceptibility to both atopy and asthma.

A simple effective clean practice protocol significantly improves hand decontamination and infection control measures in the acute surgical setting.

BACKGROUND: The Hand Hygiene Liaison Group and Epic Projects (Pratt et al., J Hosp Infect 47[Suppl A], 2001) have asked specifically for further trials of educational interventions to improve hand decontamination compliance and infection control in the hospital setting. This study investigates the efficacy of a 'clean practice protocol' (CPP), derived from international guidelines, to improve compliance of infection-control practices by surgical teams in a large UK teaching hospital. METHODS: The key infection-control activities were summated to form the CPP presented here. An undisclosed infection-control audit of consultant-led ward-rounds from breast, gastrointestinal, vascular, urological, and intensive care departments was performed. The audit results were presented to the surgical teams, after which an education/awareness program was implemented. A repeat undisclosed audit was performed 3 months later. In both audits, infection-control activities were recorded together with consultation time and any patient infective complications. RESULTS: The surgical teams performed as follows in the initial audit: hand decontamination (28% of consultations), correct use of gloves (2%), instrument cleaning (0%), garment contamination (49%), and notes contamination (34%). Introduction of the CPP education program significantly improved hand decontamination to 87% (p < 0.0001), the correct use of gloves/aprons to 50% (p < 0.0001), and overall infection-control practice from 63% to 89% (p < 0.05). CONCLUSIONS: The introduction of the CPP significantly improved compliance of hand decontamination, correct usage of gloves and aprons, and overall infection-control in a large teaching hospital. The CPP is a highly effective auditing and educational tool that can be readily adapted for use in hospitals globally to monitor and improve infection-control practices.

Orbital fibrous dysplasia with soft tissue hamartoma--a variant of Mazabraud's syndrome.

BACKGROUND: Mazabraud's syndrome was first described, by Mazabraud et al. as a rare disease, associated with single or multiple intramuscular myxomas with monostotic or polyostotic forms of fibrous dyplasia, PURPOSE: Reports of this syndrome is rare and usually associated with myoxomatas. The authors would want to report the occurrence of this rare case associated with a hamartoma as basis for record and future studies. METHOD: An adult male came to the institution 4 years ago complaining of a right unilateral proptosis that he had since childhood. However, proptosis progressed in a month's time accompanied by right eye redness. Right eye was congested with a palpable firm mass on the right lower lid. Best corrected visual acuity was 6/15-2. Pupillary examination revealed the presence of RAPD on the right eye. Exophthalmometry revealed a 10 mm proptosis. EOMS were restricted on the right eye and diplopia was noted in all gazes. Ishihara test showed 14/15 for the right eye. CT SCAN and MRI confirmed a mild inflammatory extraconal or intramuscular mass in the right obito-retrobulbar region. Bony changes seen in the right zygoma, sphenoid bone and squamous part of the temporal bone with extensive bone mineralization. The patient underwent a right lateral orbitotomy with biopsy and debulking of the inferior orbital mass. Histopathology revealed a hamartomatous lesion. CONCLUSION: Due to the associated soft tissue lesion with multiple craniofacial bone changes, this case may be considered a variant of Mazabraud's Syndrome. The associated hamatomatous lesion may be a rare occurrence that should be noted.

MUC4 and MUC5AC are highly specific tumour-associated mucins in biliary tract cancer.

Alterations in epithelial mucin expression are associated with carcinogenesis, but there are few data in biliary tract cancer (BTC). In pancreatic malignancy, MUC4 is a diagnostic and prognostic tumour marker, whereas MUC5AC has been proposed as a sensitive serological marker for BTC. We assessed MUC4 and MUC5AC expression in (i) prospectively collected bile and serum specimens from 72 patients with biliary obstruction (39 BTC) by real-time reverse transcriptase-PCR (qPCR) and western blot analysis, and (ii) 79 archived biliary tissues (69 BTC) by immunohistochemistry. In bile, MUC4 protein was detected in 27% of BTC and 29% of primary sclerosing cholangitis (PSC) cases, but not in other benign and malignant biliary diseases (P<0.01 and P=0.06). qPCR revealed a 1.9-fold increased MUC4 mRNA expression in BTC patients' bile compared with benign disease. In archived tissues, MUC4 protein was detected in 37% of BTC but in none of the benign samples (P=0.03). In serum, MUC5AC was found exclusively in BTC and PSC sera (44% and 13%, respectively; P<0.001 for BTC vs non-BTC) and correlated negatively with BTC survival. Biliary MUC4 and serum MUC5AC are highly specific tumour-associated mucins that may be useful in the diagnosis and formulation of therapeutic strategies in BTC.

[Foundations of shared decision making and examples of its application in rehabilitation]. / Grundlagen der partizipativen Entscheidungsfindung und Beispiele der Anwendung in der Rehabilitation.

Enhanced patient participation in health care is demanded due to better knowledge of patients about diseases and their treatment, due to more treatment strategies in the course of scientific progress, due to ethical and legal considerations, and due to study results. With shared decision-making (SDM) a method was defined for the medical interview to involve patients in treatment decisions. Process steps for orientation are available for the procedure of the medical encounter. Transfer of shared decision-making into health care can be realized through three strategies, i. e., by physician training to enhance physicians' competencies in medical encounter, by decision aids for better information and preparation for decision making, and by patient education. For examination and fostering of SDM in German health care the German Ministry of Health initiated a research consortium in the years 2001 to 2007 called "Patient as a partner in medical decision making". In an additional research consortium of the German Ministry of Education and Research, the German Pension Insurance scheme as well as the associations of statutory and private health insurance, various projects for health services research on the subject of "Chronic Diseases and Patient Orientation" will be funded starting in 2008. This initiative with a focus on rehabilitation will foster studies about need-specific patient information, training programmes for chronically ill patients, and about the organisation of a more participative structure of health care delivery.

Genetic regulation of MUC1 alternative splicing in human tissues.

The membrane mucin MUC1 is aberrantly expressed in a variety of cancers, and in stomach, it is a ligand for Helicobacter pylori where it plays a role in gastric carcinogenesis. Splicing variation, leading to a 9-amino acid insertion in the signal peptide region, was proposed to be because of a single-nucleotide polymorphism (rs4072037) at the 5' end of exon 2, but is also reported to be cancer-associated. However, the effect of rs4072037 on this splicing event in healthy non-cancer tissues and on the additional spliceoforms ofMUC1, including those lacking the polymorphic tandem repeat (TR) domain, has never been investigated. Here we show that in both foetal and adult tissues of known genotype, there is clear evidence for the role of rs4072037 in controlling alternative splicing of the 5' exon 2 region of both full-length transcripts and those lacking the TR domain. Although there is some evidence for additional genetic and epigenetic influences, there is no indication of an effect of the TR domain on the proportions of the spliceoforms. In conclusion, over-representation of certain transcripts in tumour material cannot be evaluated without information on the SNP genotype as well.