Implementing an interfaculty series of courses on interprofessional collaboration in prelicensure health science curriculums.

Introduction: Interprofessional collaborative practices are increasingly recognized as an effective way to deal with complex health problems. However, health sciences students continue to be trained in specialized programs and have little occasion for learning in interdisciplinary contexts. Program Development: The project's purpose was to develop content and an educational design for new prelicensure interfaculty courses on interprofessional collaboration in patient and family-centered care which embedded interprofessional education principles where participants learn with, from and about each other. Implementation: Intensive training was part of a 45-hour program, offered each semester, which was divided into three 15-hour courses given on weekends, to enhance accessibility. Evaluation: A total of 215 students completed questionnaires following the courses, to assess their satisfaction with the educational content. Pre/post measures assessed perception of skills acquisition and perceived benefits of interprofessional collaboration training. Results showed a significant increase from the students' point of view in the knowledge and benefits to be gained from interprofessional collaboration training.

Decreased Probability of Initial Pain Cessation in Classic Trigeminal Neuralgia Treated With Gamma Knife Surgery in Case of Previous Microvascular Decompression: A Prospective Series of 45 Patients With >1 Year of Follow-up.

BACKGROUND: Microvascular decompression (MVD) is the reference technique for pharmacoresistant trigeminal neuralgia (TN). OBJECTIVE: To establish whether the safety and efficacy of Gamma Knife surgery for recurrent TN are influenced by prior MVD. METHODS: Between July 1992 and November 2010, 54 of 737 patients (45 of 497 with >1 year of follow-up) had a history of MVD (approximately half also with previous ablative procedure) and were operated on with Gamma Knife surgery for TN in the Timone University Hospital. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range, 3.9-11.9 mm) anterior to the emergence of the nerve. A median maximum dose of 85 Gy (range, 70-90 Gy) was delivered. RESULTS: The median follow-up time was 39.5 months (range, 14.1-144.6 months). Thirty-five patients (77.8%) were initially pain free in a median time of 14 days (range, 0-180 days), much lower compared with our global population of classic TN (P = .01). Their actuarial probabilities of remaining pain-free without medication at 3, 5, 7, and 10 years were 66.5%, 59.1%, 59.1%, and 44.3%. The hypoesthesia actuarial rate at 1 year was 9.1% and remained stable until 12 years (median, 8 months). CONCLUSION: Patients with previous MVD showed a significantly lower probability of initial pain cessation compared with our global population with classic TN (P = .01). The toxicity was low (only 9.1% hypoesthesia); furthermore, no patient reported bothersome hypoesthesia. However, the probability of maintaining pain relief without medication was 44.3% at 10 years, similar to our global series of classic TN (P = .85). ABBREVIATIONS: BNI, Barrow Neurological InstituteCI, confidence intervalCTN, classic trigeminal neuralgiaGKS, Gamma Knife surgeryHR, hazard ratioMVD, microvascular decompressionTN, trigeminal neuralgia.

Bilateral extraperitoneal uterosacral vaginal vault suspension: a 2-year follow-up longitudinal case series of 123 patients.

INTRODUCTION AND HYPOTHESIS: The objective of this study is to assess anatomical and functional results of the extraperitoneal uterosacral ligament suspension (USL) in women with post-hysterectomy vaginal vault prolapse. METHODS: One hundred and twenty-three consecutive women were included. Concurrent procedures were anterior colporraphy with fascial repair (20%) and mesh reinforcement (49%), posterior colporraphy with fascial repair (38%) and mesh reinforcement (56%) and a sling procedure (29%). Women were assessed using Baden and Walker and pelvic organ prolapse quantification classification pre- and post-operatively. RESULTS: One hundred and ten patients (89%) were available for follow-up. Mean follow-up was 2 years. Objective success rate regarding the vaginal cuff is 95.4%. Global anatomical success rate was 85.5%. Urinary, coital and bowel symptoms were improved following surgery. Mesh exposure rate was 19.3%, with all cases managed conservatively or with minor interventions. CONCLUSION: Bilateral extraperitoneal USL is an effective operation to restore apical support with low morbidity, which avoids potential risks associated with opening the peritoneal cavity.

Changes in the use of broad-spectrum antibiotics after withdrawal of cefepime from the market: an interrupted time series analysis

Background and objective: Cefepime was one of the most used broad-spectrum antibiotics in Swiss public acute care hospitals. The drug was withdrawn from market in January 2007, and then replaced by a generic since October 2007. The goal of the study was to evaluate changes in the use of broad-spectrum antibiotics after the withdrawal of the cefepime original product. Design: A generalized regression-based interrupted time series model incorporating autocorrelated errors assessed how much the withdrawal changed the monthly use of other broad-spectrum antibiotics (ceftazidime, imipenem/cilastin, meropenem, piperacillin/ tazobactam) in defined daily doses (DDD)/100 bed-days from January 2004 to December 2008 [1, 2]. Setting: 10 Swiss public acute care hospitals (7 with\200 beds, 3 with 200-500 beds). Nine hospitals (group A) had a shortage of cefepime and 1 hospital had no shortage thanks to importation of cefepime from abroad. Main outcome measures: Underlying trend of use before the withdrawal, and changes in the level and in the trend of use after the withdrawal. Results: Before the withdrawal, the average estimated underlying trend (coefficient b1) for cefepime was decreasing by -0.047 (95% CI -0.086, -0.009) DDD/100 bed-days per month and was significant in three hospitals (group A, P\0.01). Cefepime withdrawal was associated with a significant increase in level of use (b2) of piperacillin/tazobactam and imipenem/cilastin in, respectively, one and five hospitals from group A. After the withdrawal, the average estimated trend (b3) was greatest for piperacillin/tazobactam (+0.043 DDD/100 bed-days per month; 95% CI -0.001, 0.089) and was significant in four hospitals from group A (P\0.05). The hospital without drug shortage showed no significant change in the trend and the level of use. The hypothesis of seasonality was rejected in all hospitals. Conclusions: The decreased use of cefepime already observed before its withdrawal from the market could be explained by pre-existing difficulty in drug supply. The withdrawal of cefepime resulted in change in level for piperacillin/tazobactam and imipenem/cilastin. Moreover, an increase in trend was found for piperacillin/tazobactam thereafter. As these changes generally occur at the price of lower bacterial susceptibility, a manufacturers' commitment to avoid shortages in the supply of their products would be important. As perspectives, we will measure the impact of the changes in cost and sensitivity rates of these antibiotics.

Multi-well fungal co-culture for de novo metabolite-induction in time-series studies based on untargeted metabolomics.

The induction of fungal metabolites by fungal co-cultures grown on solid media was explored using multi-well co-cultures in 2 cm diameter Petri dishes. Fungi were grown in 12-well plates to easily and rapidly obtain the large number of replicates necessary for employing metabolomic approaches. Fungal culture using such a format accelerated the production of metabolites by several weeks compared with using the large-format 9 cm Petri dishes. This strategy was applied to a co-culture of a Fusarium and an Aspergillus strain. The metabolite composition of the cultures was assessed using ultra-high pressure liquid chromatography coupled to electrospray ionisation and time-of-flight mass spectrometry, followed by automated data mining. The de novo production of metabolites was dramatically increased by nutriment reduction. A time-series study of the induction of the fungal metabolites of interest over nine days revealed that they exhibited various induction patterns. The concentrations of most of the de novo induced metabolites increased over time. However, interesting patterns were observed, such as with the presence of some compounds only at certain time points. This result indicates the complexity and dynamic nature of fungal metabolism. The large-scale production of the compounds of interest was verified by co-culture in 15 cm Petri dishes; most of the induced metabolites of interest (16/18) were found to be produced as effectively as on a small scale, although not in the same time frames. Large-scale production is a practical solution for the future production, identification and biological evaluation of these metabolites.

Epibulbar osseous choristoma: a clinicopathological case series and review of the literature [Epibulbäre knöcherne Choristome: eine klinisch-pathologische Fallserie und Überblick der Literatur]

BACKGROUND: Choristomas are benign, congenital tumours composed of normal tissue in an abnormal location. Osseous choristomas represent the rarest form of epibulbar choristomas, with now 65 cases reported in the literature. We did a retrospective clinicopathological study of all patients with epibulbar osseous choristoma observed at our institution since 1982 and updated the last review of the literature. HISTORY AND SIGNS: Three Caucasian male patients, aged between 3 months and 11 years, were identified. All osseous choristomas were located under the superotemporal bulbar conjunctiva of the right eye. THERAPY AND OUTCOME: All lesions were managed with surgical excision. Histopathology revealed the presence of lamellar bone in all cases, one of which was associated with a dermolipoma. CONCLUSIONS: We report a small rare case series of 3 epibulbar osseous choristomas and did a review of the literature. In one patient, the osteoma was associated with a dermolipoma, corresponding to the fourth reported complex choristoma of this type, in an otherwise normal eye, in the literature.

Paralyzed neonatal larynx in adduction. Case series, systematic review and analysis.

OBJECTIVE: Bilateral vocal cord abductor paralysis (BVCAbP) is considered a rare cause of stridor in the newborn. The goal of this work is to present a case series and to review systematically the literature on bilateral vocal cord abductor paralysis in the newborn to better characterize the current knowledge on this entity. METHODS: We performed a systematic literature review with Medline (1950-2011). The authors screened all cases of BVCAbP reported and selected those affecting newborns. RESULTS: Out of the 129 articles screened, 16 were included. A total of 69 cases could be retrieved and analyzed. Associated co-morbidities were found in 54% of the patients, most notably malformative conditions (intracranial or other), or a positive perinatal history (trauma/asphyxia, prematurity). Tracheostomy placement was required in 59% of children, and of these 44% were successfully decannulated. In terms of functional outcome full recovery or improvement were seen in 61% of patients. Major underlying co-morbidities affected negatively the functional outcome (p=.004), but not the need for tracheostomy (p=.604) or the decannulation success rate (p=.063). CONCLUSION: BVCAbP in the newborn is a serious cause of airway obstruction. It can be seen either in a context of multisystem anomalies or as an isolated finding. Newborns with major co-morbidities affecting their normal development are more likely to have poor functional outcomes and to remain tracheostomy-dependant.

Effect of long-term climbing training on cerebellar ataxia: a case series.

Background. Efficient therapy for both limb and gait ataxia is required. Climbing, a complex task for the whole motor system involving balance, body stabilization, and the simultaneous coordination of all 4 limbs, may have therapeutic potential. Objective. To investigate whether long-term climbing training improves motor function in patients with cerebellar ataxia. Methods. Four patients suffering from limb and gait ataxia underwent a 6-week climbing training. Its effect on ataxia was evaluated with validated clinical balance and manual dexterity tests and with a kinematic analysis of multijoint arm and leg pointing movements. Results. The patients increased their movement velocity and achieved a more symmetric movement speed profile in both arm and leg pointing movements. Furthermore, the 2 patients who suffered the most from gait ataxia improved their balance and 2 of the 4 patients improved manual dexterity. Conclusion. Climbing training has the potential to serve as a new rehabilitation method for patients with upper and lower limb ataxia.

Epibulbar osseous choristomaa clinicopathological case series and review of the literature

Background:¦Choristomas are benign, congenital tumours composed of normal tissue in an¦abnormal location. Osseous choristomas represent the rarest form of epibulbar choristomas,¦with now 65 cases reported in the literature. We did a retrospective clinicopathological study¦of all patients with epibulbar osseous choristoma observed at our institution since 1982 and¦updated the last review of the literature.¦History and Signs:¦Three Caucasian male patients, aged between 3 months and 11 years,¦were identified. All osseous choristomas were located under the superotemporal bulbar¦conjunctiva of the right eye.¦Therapy and Outcome:¦All lesions were managed with surgical excision. Histopathology¦revealed the presence of lamellar bone in all cases, one of which was associated with a¦dermolipoma.¦Conclusions:¦We report a small rare case series of 3 epibulbar osseous choristomas and did a¦review of the literature. In one patient, the osteoma was associated with a dermolipoma,¦corresponding to the fourth reported complex choristoma of this type, in an otherwise normal¦eye, in the literature.

Expression of MYC, IgM, As Well As Non-Germinal Centre B-Cell Like Immunophenotype and Positive Immunofish Index Predict a Worse Progression Free Survival and Overall Survival in a Series of 670 De Novo Diffuse Large B-Cell Lymphomas Included in Clinical Trials: A GELA Study of the 2003 Program

Introduction: Diffuse large B-cell lymphomas (DLBCL) represent a heterogeneous disease with variable clinical outcome. Identifying phenotypic biomarkers of tumor cells on paraffin sections that predict different clinical outcome remain an important goal that may also help to better understand the biology of this lymphoma. Differentiating non-germinal centre B-cell-like (non-GCB) from Germinal Centre B-cell-like (GCB) DLBCL according to Hans algorithm has been considered as an important immunohistochemical biomarker with prognostic value among patients treated with R-CHOP although not reproducibly found by all groups. Gene expression studies have also shown that IgM expression might be used as a surrogate for the GCB and ABC subtypes with a strong preferential expression of IgM in ABC DLBCL subtype. ImmunoFISH index based on the differential expression of MUM-1, FOXP1 by immunohistochemistry and on the BCL6 rearrangement by FISH has been previously reported (C Copie-Bergman, J Clin Oncol. 2009;27:5573-9) as prognostic in an homogeneous series of DLBCL treated with R-CHOP. In addition, oncogenic MYC protein overexpression by immunohistochemistry may represent an easy tool to identify the consequences of MYC deregulation in DLBCL. Our aim was to analyse by immunohistochemistry the prognostic relevance of MYC, IgM, GCB/nonGCB subtype and ImmunoFISH index in a large series of de novo DLBCL treated with Rituximab (R)-chemotherapy (anthracyclin based) included in the 2003 program of the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials. Methods: The 2003 program included patients with de novo CD20+ DLBCL enrolled in 6 different LNH-03 GELA trials (LNH-03-1B, -B, -3B, 39B, -6B, 7B) stratifying patients according to age and age-adjusted IPI. Tumor samples were analyzed by immunohistochemistry using CD10, BCL6, MUM1, FOXP1 (according to Barrans threshold), MYC, IgM antibodies on tissue microarrays and by FISH using BCL6 split signal DNA probes. Considering evaluable Hans score, 670 patients were included in the study with 237 (35.4%) receiving intensive R-ACVBP regimen and 433 (64.6%) R-CHOP/R-mini-CHOP. Results: 304 (45.4%) DLBCL were classified as GCB and 366 (54.6%) as non-GCB according to Hans algorithm. 337/567 cases (59.4%) were positive for the ImmunoFISH index (i.e. two out of the three markers positive: MUM1 protein positive, FOXP1 protein Variable or Strong, BCL6 rearrangement). Immunofish index was preferentially positive in the non-GCB subtype (81.3%) compared to the GCB subtype (31.2%), (p<0.001). IgM was recorded as positive in tumor cells in 351/637 (52.4%) DLBCL cases with a preferential expression in non-GCB 195 (53.3%) vs GCB subtype 100(32.9%), p<0.001). MYC was positive in 170/577 (29.5%) cases with a 40% cut-off and in 44/577 (14.2%) cases with a cut-off of 70%. There was no preferential expression of MYC among GCB or non-GCB subtype (p>0.4) for both cut-offs. Progression-free Survival (PFS) was significantly worse among patients with high IPI score (p<0.0001), IgM positive tumor (p<0.0001), MYC positive tumor with a 40% threshold (p<0.001), ImmunoFISH positive index (p<0.002), non-GCB DLBCL subtype (p<0.0001). Overall Survival (OS) was also significantly worse among patients with high IPI score (p<0.0001), IgM positive tumor (p=0.02), MYC positive tumor with a 40% threshold (p<0.01), ImmunoFISH positive index (p=0.02), non-GCB DLBCL subtype (p<0.0001). All significant parameters were included in a multivariate analysis using Cox Model and in addition to IPI, only the GCB/non-GCB subtype according to Hans algorithm predicted significantly a worse PFS among non-GCB subgroup (HR 1.9 [1.3-2.8] p=0.002) as well as a worse OS (HR 2.0 [1.3-3.2], p=0.003). This strong prognostic value of non-GCB subtyping was confirmed considering only patients treated with R- CHOP for PFS (HR 2.1 [1.4-3.3], p=0.001) and for OS (HR 2.3 [1.3-3.8], p=0.002). Conclusion: Our study on a large series of patients included in trials confirmed the relevance of immunohistochemistry as a useful tool to identify significant prognostic biomarkers for clinical use. We show here that IgM and MYC might be useful prognostic biomarkers. In addition, we confirmed in this series the prognostic value of the ImmunoFISH index. Above all, we fully validated the strong and independent prognostic value of the Hans algorithm, daily used by the pathologists to subtype DLBCL.

Prenatal diagnosis of urinary malformations: results in a series of 93 consecutive cases.

OBJECTIVE: To evaluate the pertinence of prenatal diagnosis in cases of congenital uropathy. STUDY DESIGN: Retrospective evaluation over a period of 6.5 years. METHOD: 93 cases were involved in the comparison of prenatal ultrasonographic diagnosis with neonatal findings, autopsy results, and follow-up data. RESULTS: 33 fetuses had renal parenchymal lesions, 44 had excretory system lesions, and 6 had bladder and/or urethral lesions. Seventy-three pregnancies lead to live births. Eighteen terminations of pregnancy were performed on the parents' request for extremely severe malformations. Two intrauterine deaths were observed, and two infants died in the postnatal period. Prenatal diagnosis was obtained at an average of 27 weeks gestation. Diagnostic concordance was excellent in 82% and partial in 12% of cases with renal parenchymal lesions; the false-positive rate was 6%. For excretory system lesions, concordance was excellent in 87% and partial in 7.4% of cases, with a false-positive rate of 5.6%. Finally, concordance was excellent in 100% of cases of bladder and/or urethral lesions. The overall rate of total concordance was 86%. Partial concordance cases consisted of malformations different from those previously diagnosed, but prenatal diagnosis nevertheless lead to further investigations in the neonatal period and to proper management. The false-positive diagnoses (5.4%) never lead to termination of pregnancy. CONCLUSION: Prenatal diagnosis of congenital uropathy is effective. A third-trimester ultrasonographic examination is necessary to ensure proper neonatal management, considering that the majority of cases are diagnosed at this gestational age.

Inverse metamorphic zonation in very low-grade Tibetan zone series of SE Zanskar and its tectonic consequences (NW India, Himalaya)

The metamorphism of the carbonate rocks of the SE Zanskar Tibetan zone has been studied by `'illite crystallinity'' and calcite-dolomite thermometry. The epizonal Zangla unit overlies the anchizonal Chumik unit. This discontinuous inverse zonation demonstrates a late to post-metamorphic thrust of the first unit over the second. The studied area underwent a complex tectonic history: - The tectonic units were stacked from the NE to the SW, generating recumbent folds, NE dipping thrusts and the regional metamorphism. The compressive movements were active under lower temperature conditions, resulting in late thrusts that disturbed the metamorphic zonation. The discontinuous inverse metamorphic zonation dates from this phase. - A NE vergent backfolding phase occurred at lower temperature conditions. It caused the uplift of more metamorphic levels. - A late extensional phase is revealed by the presence of NE dipping low angle normal faults, and a major high angle fault, the Sarchu fault. The low angle normal faults locally run along earlier thrusts (composite tectonic contacts). Their throw has been sufficient to reset a normal stratigraphic superposition (young layers overlying old ones), but insufficient to erase the inverse metamorphic relationship. However, the combined action of backfolding and normal faulting can locally lessen, or even cancel, the inverse metamorphic superposition. After deduction of the normal fault translation, the vertical component of the original thrust displacement through stratigraphy is 400 m, which is a value far too low to explain the temperature difference between the two units. The horizontal component of displacement is therefore far more important than the vertical one. The regional distribution of metamorphism within the Zangla unit points out to an anchizonal front and an epizonal inner part. This fact is in agreement with nappe tectonics.

Highly diverse T cell recognition of a single Plasmodium berghei peptide presented by a series of mutant H-2Kd molecules.

We have tested 21 independent CTL clones for recognition of a single peptide derived from the Plasmodium berghei circumsporozoite protein in the context of 13 mutants of the murine MHC class I molecule H-2Kd. In this series of Kd mutants, amino acid residues located on the upper surface of the alpha-helices were individually substituted by alanine. Remarkably, most clones displayed individual recognition patterns on the Kd mutants. We had previously found that this series of CTL clones was likewise highly diverse in terms of both TCR primary structure and peptide fine specificity. Our data thus reinforce the concept that multiple T cell epitopes are available on the surface of a single peptide-MHC class I complex for recognition by specific TCR.