Characterisation of subchondral bone repair following transplantation of bioreactor-manufactured autologous osteochondral graft in a sheep model.

To date, no single approach to the treatment of osteochondral defects has resulted in satisfactory long-term outcomes, especially in a young and active human population. Emerging innovative tissue engineering strategies, including the use of composite scaffolds, novel cell sources and bioreactors, have shown promising results. However, these techniques need to be validated in translational animal models before they can be implemented in clinical practice. The aim of the present study was to analyse morphological and microarchitectural parameters during subchondral bone repair following transplantation of bioreactor-manufactured autologous osteochondral grafts in a sheep model. Animals were divided into 4 treatment groups: nasal chondrocyte (NC) autologous osteochondral grafts, articular chondrocyte (AC) autologous osteochondral grafts, cell-free scaffolds (CFS) and empty defects (EDs). After 6 weeks, 3 months and 12 months, bone remodelling was assessed by histology and micro-computed tomography (µCT). Although gradual remodelling and subchondral bone repair were seen in all groups across the time points, the best results were observed in the NC group. This was evidenced by the extent of new tissue formation and its best integration into the surrounding tissue in the NC group at all time points. This also suggested that nasal septum chondrocyte-seeded grafts adapted well to the biomechanical conditions of the loaded joint surface.

Proteomic analysis of peritoneal fluid identified COMP and TGFBI as new candidate biomarkers for endometriosis.

Endometriosis is a common non-malignant gynecological disease that significantly compromises fertility and quality of life of the majority of patients. The gold standard for diagnosis is visual inspection of the pelvic organs by surgical laparoscopy and there are no biomarkers that would allow non-invasive diagnosis. The pathogenesis of endometriosis is not completely understood, thus analysis of peritoneal fluid might contribute in this respect. Our prospective case-control study included 58 patients undergoing laparoscopy due to infertility, 32 patients with peritoneal endometriosis (cases) and 26 patients with unexplained primary infertility (controls). Discovery proteomics using antibody microarrays that covered 1360 proteins identified 16 proteins with different levels in cases versus the control patients. The validation using an ELISA approach confirmed significant differences in the levels of cartilage oligomeric matrix protein (COMP) and transforming growth factor-ß-induced protein ig-h3 (TGFBI) and nonsignificant differences in angiotensinogen (AGT). A classification model based on a linear support vector machine revealed AUC of > 0.83, sensitivity of 0.81 and specificity of 1.00. Differentially expressed proteins represent candidates for diagnostic and prognostic biomarkers or drug targets. Our findings have brought new knowledge that will be helpful in the understanding of the pathophysiology of endometriosis and warrant further studies in blood samples.

Deliberate practice as an educational method for learning to interpret the prepubescent female genital examination.

BACKGROUND: Correct interpretation of the prepubescent female genital examination is a critical skill; however, physician skill in this area is limited. OBJECTIVE: To complement the bedside learning of this examination, we developed a learning platform for the visual diagnosis of the prepubescent female genital examination and examined the amount and rate of skill acquisition. PARTICIPANTS AND SETTING: Medical students, residents, and fellows and attendings participated in an on-line learning platform. METHODS: This was a multicenter prospective cross-sectional study. Study participants deliberately practiced 158 prepubescent female genital examination cases hosted on a computer-based learning and assessment platform. Participants assigned the case normal or abnormal; if abnormal, they identified the location of the abnormality and the specific diagnosis. Participants received feedback after every case. RESULTS: We enrolled 107 participants (26 students, 31 residents, 24 fellows and 26 attendings). Accuracy (95 % CI) increased by 10.3 % (7.8, 12.8), Cohen's d-effect size of 1.17 (1.14, 1.19). The change in specificity was +16.8 (14.1, 19.5) and sensitivity +2.4 (-0.9, 5.6). It took a mean (SD) 46.3 (32.2) minutes to complete cases. There was no difference between learner types with respect to initial (p = 0.2) or final accuracy (p = 0.4) scores. CONCLUSIONS: This study's learning intervention led to effective and feasible skill improvement. However, while participants improved significantly with normal cases, which has relevance in reducing unnecessary referrals to child protection teams, learning gains were not as evident in abnormal cases. All levels of learners demonstrated a similar performance, emphasizing the need for this education even among experienced clinicians.

Factors influencing medical student attrition and their implications in a large multi-center randomized education trial.

Participant attrition may be a significant threat to the generalizability of the results of educational research studies if participants who do not persist in a study differ from those who do in ways that can affect the experimental outcomes. A multi-center trial of the efficacy of different computer-based instructional strategies gave us the opportunity to observe institutional and student factors linked to attrition from a study and the ways in which they altered the participation profile. The data is from a randomized controlled trial conducted at seven US medical schools investigating the educational impact of different instructional designs for computer-based learning modules for surgical clerks. All students undertaking their surgical clerkships at the participating schools were invited participate and those that consented were asked to complete five study measures during their surgery clerkship. Variations in study attrition rates were explored by institution and by participants' self-regulation, self-efficacy, perception of task value, and mastery goal orientation measured on entry to the study. Of the 1,363 invited participants 995 (73 %) consented to participate and provided baseline data. There was a significant drop in the rate of participation at each of the five study milestones with 902 (94 %) completing at least one of two module post-test, 799 (61 %) both module post-tests, 539 (36 %) the mid-rotation evaluation and 252 (25 %) the final evaluation. Attrition varied between institutions on survival analysis (p < 0.001). Small but statistically significant differences in self-regulation (p = 0.01), self-efficacy (p = 0.02) and task value (p = 0.04) were observed but not in mastery or performance goal orientation measures (p = NS). Study attrition was correlated with lower achievement on the National Board of Medical Examiners subject exam. The results of education trials should be interpreted with the understanding that students who persist may be somewhat more self-regulated, self-efficacious and higher achievers than their peers who drop out and as such do not represent the class as a whole.

The effect of certain biochemical factors on well clogging under suboxic and mildly anoxic conditions.

Research conducted at the Belgrade Groundwater Source in Serbia has shown that significant well screen clogging processes take place under reduced oxic and initial anoxic conditions. Criteria for the prevention, or deceleration, of clogging are becoming more relevant to well ageing, compared with classical, mechanical clogging criteria and the permissible entrance velocities derived from them. The research project was later expanded to encompass other alluvial sources, which feature distinct oxic conditions. This paper presents some of the outcomes of this project, which shed light on the correlation between certain important indicators of well screen clogging (such as the redox potential and iron concentration) and the rate of increase in local hydraulic resistance at the wells.

Water quality as an indicator of hydrogeological conditions: a case study of the Belgrade Groundwater Source (Sava/Danube confluence area).

The City of Belgrade receives most of its drinking water supply from the alluvial aquifer of the Sava River. The wells are radial, placed in the lower part of the aquifer, so they partly run below the Sava riverbed. However, the groundwater quality of the wells in one part of the source (near the confluence of the Sava and Danube rivers) is found to differ somewhat from the groundwater quality of the other wells. The finding gave rise to additional investigations. The results revealed the existence of a deeper, limestone aquifer which is isolated from upper alluvial sediments by a thick layer of clay in most of the terrain. The naturally potential hydraulic contact of the two aquifers was additionally maintained by well operation in this part of the source. According to multiple analyses of groundwater flow using a hydrodynamic mathematical model, a hydrogeological and hydraulic system of groundwater flow was defined. Although the wells are situated adjacent to the river, and some well laterals are below the riverbed, most of the groundwater that flows to the wells is partly from the wider zone of the alluvial aquifer, and partly from the deeper aquifer. The initial results of hydrochemical investigations also showed an unexpected, inverse oxic character of the groundwater in these two aquifers.

Unusual consecutive sacral stress fractures in a female distant runner: a case report.

Sacral stress fractures are rare overuse injuries predominantly perceived in female long-distance runners. Our case report describes left-sided sacral wing stress fracture followed by contralateral sacral wing fracture after return to running. A 21-year-old female amateur long-distance runner presented with nonspecific low back and left buttock pain. Plain radiograph at presentation was unremarkable. Magnetic resonance imaging (MRI) revealed extensive bone marrow oedema in the cranial part of the left sacral wing and oblique fracture line. After six weeks of moderate training and two months of tailored running program she felt sharp pain in her right buttock during landing on her right leg. MRI confirmed contralateral sacral wing stress fracture. Additional two-month program to correct lumbar hyperlordotic posture with relaxation techniques and stretching of quadratus lumborum, psoas, multifidus and rectus femoris muscles was carried out. Strengthening of the abovementioned muscles was also done together with abdominal wall muscles and gluteals to stabilize the lumbar spine. She regained full level of training six months after the second fracture. Two years after the second stress fracture of the sacral wing she is free of pain, running about 60 to 70 km per week. Despite rapid rehabilitation program after first sacral stress fracture, contralateral stress fracture occurred. After a few months of additional conditional training and strengthening of lumbar, abdominal and pelvic muscles she regains her long-distance running including four marathons without obstacles. From this case we can assume that following proper rehabilitation program with correction of hyperlordotic posture sacral stress fractures can be avoided.

Several natural indicators of radial well ageing at the Belgrade groundwater source, part 1.

Over time, the radial collector wells of the Belgrade Groundwater Source, located in the alluvial sediments of the Sava River, exhibit a decline in discharge and a reduction in operating efficiency due to well ageing. An increase in hydraulic losses at the lateral screens, due to chemical and biochemical clogging, has been identified as the primary cause. Certain hydrogeological, hydrochemical and microbiological parameters reflect the well-ageing process and can, therefore, be considered as its indicators. An indicator-based determination of scale is an important aspect in the selection of appropriate well locations, structural characteristics, and maintenance approaches. Well ageing was studied over a period of 5 years (2005-2009). The objective was to investigate the causes of well ageing. The correlations established between the groundwater redox potential, the total iron concentration in groundwater, the grain-size distribution of the aquifer, and well discharge, are presented in the paper.

Several natural indicators of radial well ageing at the Belgrade groundwater source, part 2.

From 2005 to 2009, research was conducted at the Belgrade Groundwater Source (BGWS) to investigate the process of clogging of wells with horizontal lateral screens (radial wells). The clogging process was monitored via the kinetics of the increase in hydraulic losses at the laterals. A correlation of this process with the redox potential, the iron concentration in water, and the microbial population growth at the laterals and in their immediate vicinity was established. Research outcomes are presented here from a study of five wells where laterals were replaced between 2006 and 2008. Derived dependencies were later used to define the preferred approach to the installation and maintenance of well laterals at the BGWS. Results contribute to the study of well ageing caused by biochemical clogging.

Effect of a clinical pathway on the hospitalisation rates of children with asthma: a prospective study.

AIM: To determine the effect of implementing a clinical pathway, using evidence-based clinical practice guidelines, for the emergency care of children and adolescents with asthma. METHODS: A prospective, before-after, controlled trial was conducted, which included patients aged 1-18 years who had acute exacerbations of asthma treated in a tertiary care paediatric emergency department. Data were collected for identical 2-month seasonal periods before and after implementation of the clinical pathway to determine hospitalisation rate and other outcomes. For 2 weeks after emergency visits, the rate at which patients returned to emergency care for worsening asthma was evaluated. A multidisciplinary panel, using national guidelines and a systematic review, developed the pathway. RESULTS: 267 patients were studied. The rate of hospitalisation was significantly lower in the post-implementation group (10/74; 13.5%) than in the pre-implementation control group (53/193; 27.5%; p = 0.02; number needed to treat 7.1). All reduction in hospitalisation occurred in children with moderate to severe asthma exacerbation. After implementation of the clinical pathway, the rate of administration of oral corticosteroids to patients with moderate or severe exacerbations increased from 71% to 92% (p = 0.01), and significantly more patients received beta2-agonists in the first hour (p = 0.02). No significant change in relapse to acute care occurred within 2 weeks (p = 0.19). CONCLUSIONS: An evidence-based clinical pathway for children and adolescents with moderate to severe exacerbations of acute asthma markedly decreases their rate of hospitalisation without increased return to emergency care.

E-mail amplification of a mock code teaching round.

To determine whether e-mail could be used to supplement a teaching round, we implemented the following educational intervention: each Monday, a mock code was presented. Two e-mails were then sent the same day to all residents. One summarized the main teaching points whereas the second solicited discussion. Each Friday, a third e-mail was sent that summarized the discussion. We collected all e-mails and surveyed the residents. Fifteen of 18 residents completed the questionnaire; two were not participants in the e-round. Forty percent (7/15) of the residents attended fewer than half of the mock codes but most participants (10/13) reported reading >95% of the e-mails. A majority reported storing (11/13), printing (7/13), and reading e-mails a second time (12/13). Seven of 13 reported learning as much or more from the e-mails as from the mock code itself. We conclude that e-mail can increase learning from a traditional mock code teaching round.

Utilization of a pediatric emergency department education computer.

OBJECTIVE: To describe the use of a computer education station placed within a pediatric emergency department. DESIGN: Prospective tracking of computer tutorial use. SETTING: A tertiary care pediatric emergency department. METHODS: A computer with two 30-minute multimedia computer tutorials was installed in the emergency department. The tutorials were designed for residents to use on a voluntary basis but were available to medical students and allied health professionals as well. Software tracked time, date, duration of use, and the user's path through each tutorial. Data were collected from July 15, 1996, through April 30, 1997. RESULTS: Twenty-eight residents interacted 71 times with the computer during the study. The mean duration of interactions was 22 minutes (SD, 18 minutes; range, 0-75 minutes), but many lasted less than 5 minutes (15 [21%] of 71). Twenty-four (34%) of the interactions led to tutorial completion. Residents were more likely to complete a tutorial during the day shift (22 [40%] of 55) compared with the evening shift (1 [7%] of 14) (P =.02). A third of the interactions were during evenings and weekends. The education station delivered 26.1 hours of instruction in total. Of 32 first-year pediatric and emergency medicine residents, 22 attempted the tutorials; 4 completed both, and 10 completed one. Allied health professionals were responsible for 28% of the total interactions. They were significantly more likely than medical trainees to have brief interactions, but they were no less likely to complete the tutorials (10 [22%] of 46 vs 31 [27%] of 115; P =.44). CONCLUSIONS: Pediatric residents are willing to use an educational computer placed in the emergency department. Choice of form and content should take into account the likelihood of short interactions and the demonstrated interest of allied health professionals.

Ipratropium bromide added to asthma treatment in the pediatric emergency department.

OBJECTIVE: To determine if the addition of ipratropium bromide to the emergency department (ED) treatment of childhood asthma reduces time to discharge, number of nebulizer treatments before discharge, and the rate of hospitalization. METHODS: Patients >12 months of age were eligible if they were to be treated according to a standardized ED protocol for acute asthma with nebulized albuterol (2.5 mg/dose if weight <30 kg, otherwise 5 mg/dose) and oral prednisone or prednisolone (2 mg/kg up to 80 mg). Subjects were randomized to receive either ipratropium (250 microg/dose) or normal saline (1 mL/dose) with each of the first three nebulized albuterol doses. Further treatment after the first hour was determined by physicians blinded to subject group assignment. Records were reviewed to determine the length of time to discharge home from the ED, number of doses of albuterol given before discharge, and the number of patients admitted to the hospital. RESULTS: Four hundred twenty-seven patients were randomized to ipratropium or control groups; these groups were similar in all baseline measures. Among patients discharged from the ED, ipratropium group subjects had 13% shorter treatment time (mean, 185 minutes, vs control, 213 minutes) and fewer total albuterol doses (median, three, vs control, four). Admission rates did not differ significantly (18%, vs control, 22%). CONCLUSIONS: The addition of three doses of ipratropium to an ED treatment protocol for acute asthma was associated with reductions in duration and amount of treatment before discharge.

Pediatric residents: are they ready to use computer-aided instruction?

OBJECTIVE: To assess pediatric residents' readiness to use computer-aided instruction (CAI). DESIGN: Survey. SETTING: Pediatric residency program based in a tertiary care children's hospital. PARTICIPANTS: Four pediatric residency classes. ASSESSMENT INSTRUMENT: Self-administered questionnaire. MAIN OUTCOME MEASURES: Residents' access to computers and the Internet, experience with CD-ROM and World Wide Web computer tutorials, and attitudes toward CAI. Responses were stratified by age, training level, sex, and previous computer education. RESULTS: Fifty-one (69%) of the residents owned a computer. Men were more likely than women to own a computer (20 [87%] of 23 men vs 31 [61%] of 51 women; P=.02). Medical education software was used by 18 (28%) of 65, but only 2 (4%) of 74 had ever purchased CAI. Twenty-seven (36%) of 74 regularly accessed medical education World Wide Web sites. Nineteen (26%) of 74 had never accessed the Internet. Of those who had, 50 (91%) of 55 continued to do so at least weekly. Eighteen (95%) of the 19 residents who had never accessed the Internet were female (P=.005). Men were twice as likely to have Internet access at home (P=.01) and were more likely to regularly visit medical education World Wide Web sites (P=.02). Attitudes toward CAI were positive. Most respondents would be willing to use CAI developed at their institution. Most residents ranked CAI ahead of printed teaching materials but behind personal teaching by a pediatrician. Attitudes did not differ by sex. CONCLUSION: Despite positive attitudes toward CAI, pediatric residents are not yet universally ready to use CAI.

Mycobacterial brain abscess possibly due to bacille Calmette-Guérin in an immunocompromised child.

Disseminated infection with bacille Calmette-Guérin (BCG) is rare, even in immunocompromised patients who receive BCG injections as immunotherapy or immunization. When such infection occurs, it is usually in patients with decreased cellular immunity. A 6-year-old Caucasian girl who was receiving maintenance chemotherapy for acute lymphoblastic leukemia presented with symptoms of meningitis. A temporal-lobe biopsy revealed acid-fast bacilli that were identified as Mycobacterium bovis BCG. Neither the patient nor any family members had been immunized previously. Appropriate therapy resulted in a complete recovery.