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Perioperative antibiotic prophylaxis has been a mainstay of orthopaedic trauma care for decades. Despite ongoing controversy regarding the optimal number of doses required, established guidelines for use have been in place for years. A retrospective quality assurance project was conducted in Calgary, Alberta, Canada, to review local practice regarding perioperative antibiotic administration in orthopaedic trauma and compare that to what is suggested in the literature.

Background Laparoscopic surgery (LS) is contemplated during long duration space flight, but it typically necessitates intraabdominal hypertension (IAH) from insufflation to create a surgical domain. Because there are spontaneous changes in abdominal wall behavior in weightlessness (0g) that have been previously suggested to increase LS visualization, we studied the comparative laparoscopic visualization between gasless (noGAS), abdominal wall retraction (AWR), and standard 15 mmHg gas insufflation (GAS) during weightlessness. Study Design In-flight LS was performed on four anesthetized pigs during weightlessness obtained through parabolic flight in a research aircraft. GAS was studied during 27 parabolas and compared with 20 parabolas using AWR-LS and 12 with noGAS. Pelvic visualization was scored in real time during flight by 2 or 3 surgeons per parabola and postflight through review of compiled digital video disk (DVD) images by 29 independent reviewers. Physical measurements of the sagittal (anterior-posterior) and transverse dimensions of anesthetized pigs were recorded during 39 parabolas. Results Despite consistent increases in the sagittal abdominal dimension in weightlessness (GAS and noGAS), on-board scored visualization in 0g was unchanged for noGAS (p=0.78) and decreased during AWR (p=0.09), compared with 1g. Although AWR was considered feasible in 1g, spontaneous visceral movements reduced the surgical domain in 0g. Neither AWR nor noGAS was believed safe. But visualization during GAS in 0g was increased over that in 1g (p Conclusions Both noGAS and AWR are impractical in weightlessness. Gas insufflation will be required. With insufflation, visualization and perceived ability to perform LS was improved by weightlessness.

Laparoscopic surgery (LS) is envisioned as an option for spaceflight, but requires intra-abdominal hypertension (IAH) to create the surgical domain. Prolonged weightlessness induces physiologic deconditioning that questions the ability of ill or injured astronauts to tolerate IAH. On earth, IAH results in marked ventilatory embarrassment. As there has been no previous study of physiologic changes related to LS in weightlessness, we studied anesthetized pigs in parabolic flight.Parabolic flight research laboratory.Five anesthetized Yorkshire pigs.Subjects were transported from an animal care facility and secured aboard an aircraft capable of generating hypergravity and weightlessness. Mechanical ventilation was performed using pressure control and positive end-expiratory pressure at 15 and 2 cm H2O, respectively; rate 12 breaths/min. Three abdominal conditions were used during LS: insufflation to produce IAH, abdominal wall retraction (AWR), and no abdominal wall manipulation (baseline). During each parabola breath by breath-tidal volumes (Vt) were recorded by a transport ventilator (HT-50 Newport Medical).Least square means (LS-means) of weight corrected Vt (milliliter per kilogram) by gravity (g) and abdominal condition were determined using a mixed effects model for repeated measures analysis. Increasing gravity (g) consistently reduced Vt (p = 0.0011) as did insufflation (p0.0001). In 1g, Vt (LS-mean 13.7, 95% confidence interval [CI]: 12.4-15.0) was relatively unaffected by AWR (LS-mean 12.8, 95% CI: 11.5-14.00), but markedly decreased by IAH (LS-mean 10.00, 95% CI: 8.9-11.1), an effect accentuated in hypergravity (LS-mean 8.1, 95% CI: 6.4-9.8). In weightlessness, Vt reduction during insufflation was near obviated (LS-mean 12.3, 95% CI: 10.6-14.1), and AWR regularly but inconsistently increased the Vt above 1g baseline (LS-mean 13.7, 95% CI: 11.7-15.8).Weightlessness protects against thoracic compliance changes that are inherent in IAH during induced pneumoperitoneum in gravity. The technique-related physiologic cost of performing LS in space deconditioned astronauts should be incorporated into design concepts for space surgery systems.

Objective. To evaluate the influence of average family income in a geographic area on the effectiveness of helmet legislation on observed helmet use by children (5–14 years).Methods. The study was conducted in East York, a health district of Metropolitan Toronto, in collaboration with the East York Health Unit. In 1996, the total population was 107 822, 11 340 of which were children 5 to 14 years. Census data were used to group the 21 census tracts in East York into 7 geographically distinct areas. The boundaries of these areas are natural barriers to travel, such as expressways, ravines, railway tracks, and hydroelectric power lines. The areas were also ranked according to average family income (based on Statistics Canada data). For analytical purposes, areas were defined as low-, mid-, and high-income areas. Census data profiles of the areas have been previously described. For each consecutive year from 1990 to 1997 inclusive, direct observations of children riding bicycles in East York during the months of April through October were made. In 1995, observations were completed before the introduction of the law on October 1, 1995. Only children who were between 5 and 14 years of age and riding a 2-wheeled bicycle were included in the study. In total, 111 sites across all 7 areas were selected for observation. Observational sites included school yards of all elementary and middle schools (kindergarten to grade 8) and all parks in East York. In addition, 5 major intersections and 5 residential streets from each area were randomly selected. Observers were trained and used a standardized data collection form. A pilot study showed that the data collected by observers were reliable and valid. Observers remained at each site for 1 hour and collected data on helmet use and sex. Ethical approval for the study was obtained from the Hospital for Sick Children Research Ethics Board, the East York Board of Education, and the Metropolitan Separate School Board. The proportion of children who were wearing a bicycle helmet was estimated by year (1990–1997, inclusive), sex (male, female), location (school, park, major intersection, residential street), and income area (low, mid, high). For estimating the effect of legislation on helmet use, data from the year immediately after legislation (1996) were compared with data from the year preceding legislation (1995). The relative risk (RR) of helmet use (after vs before legislation) was calculated along with a 95% confidence interval (CI). Logistic regression analysis was used to adjust for potential confounding variables (sex and location).Results. During the 8-year study period, 9768 observations were made (range: 914-1879 observations per year). The proportion of child cyclists who wore a bicycle helmet increased steadily during the first 4 years of the study period, from 4% in 1990 (34 of 914), to 16% in 1991 (303 of 1879), to 25% in 1992 (383 of 1563), and to 45% in 1993 (438 of 984). During 1994 (460 of 1083) and 1995 (568 of 1227), helmet use remained relatively stable at approximately 44%. Helmet use rose markedly in 1996 (the first year after helmet legislation was introduced) to 68% (818 of 1202) and remained stable at 66% (609 of 916) in 1997. Throughout the study period, girls were consistently more likely to wear helmets than were boys. In total, 47% (1420 of 3047) of girls wore helmets, compared with 33% (2193 of 6721) of boys (RR: 1.43; 95% CI: 1.36–1.50). In addition, children who were riding to school were more likely to use helmets, compared with children who were riding on residential streets, major intersections, and parks. Overall, 48% (1497 of 3129) of children who were riding to school wore bicycle helmets, compared with 32% (2116 of 6639) of children who were riding at other locations (RR: 1.50; 95% CI: 1.43–1.58). Children in the high-income areas were consistently more likely to wear helmets, compared with children in the mid- and low-income areas. Helmet legislation was associated with a significant increase in helmet use by children in East York. In 1995, 46% (568 of 1227) of children wore bicycle helmets, compared with 68% (818 of 1202) of children in 1996 (RR: 1.47; 95% CI: 1.37–1.58). The effect of legislation, however, varied by income area. In low-income areas, helmet use increased by 28% after legislation, from 33% (213 of 646) in 1995 to 61% (442 of 721) in 1996 (RR: 1.86; 95% CI: 1.64–2.11). In mid-income areas, helmet use increased by 29% after legislation, from 50% (150 of 300) in 1995 to 79% (185 of 234) in 1996 (RR: 1.58; 95% CI: 1.39–1.80). In high-income areas, helmet use increased by only 4%, from 73% (205 of 281) in 1995 to 77% (191 of 247) in 1996 (RR: 1.06; 95% CI: 0.96–1.17). This finding of a significant increase in helmet use after legislation in low- and mid-income areas but not in high-income areas remained even after logistic regression analysis adjusted for sex and location.Conclusions. This study showed that bicycle helmet use by children increased significantly after helmet legislation. In this urban area with socioeconomic diversity and in the context of prelegislation promotion and educational activities, the legislative effect was most powerful among children who resided in low-income areas.

Background The management of pneumothoraces detected on CT but not on supine chest radiographs remains controversial, especially in those undergoing positive pressure ventilation (PPV) who are at risk for complications with both observation and treatment. Previous limited study yielded confusion regarding the need for routine drainage of these occult pneumothoraces (OPTXs). We conducted a pilot study at 2 trauma centers to address the feasibility and safety of randomizing traumatized patients undergoing PPV to drainage or observation. Methods Stable mechanically ventilated (or en route to surgery) adults with OPTXs were identified at 2 centers (Calgary and Quebec). Patients were randomized to observation (unless drainage became clinically indicated) or to chest drainage. Episodes of respiratory distress (need for thoracostomy tube, acute/sustained increase in oxygen requirements, difficulty in achieving adequate ventilation and self-reported distress) and subsequent imaging abnormalities were recorded until discharge. Results From August 2006 to April 2008, 24 trauma patients were enrolled (17 Calgary and 7 Quebec), with 2 later exclusions (final CT found no OPTX). Thirteen patients (59%) were randomized to observation, 9 to drainage (41%). Four observed (31%) later had chest tubes placed nonurgently for worsening OPTXs/effusions; none with increased morbidity. Overall rates of respiratory distress (drainage: 33%, observation: 41%) and mortality (drainage: 22%, observation: 15%) were similar across groups, as were median intensive care unit (drainage: 3, observation: 4) and in-hospital days (drainage: 10, observation: 16). Conclusions With no important differences in morbidity, the OPTICC pilot lays the foundation for a future definitive trial comparing drainage or observation in posttraumatic OPTXs requiring PPV.

Background: Deletion of chromosome 13 (del13) and t(4;14) in multiple myeloma (MM) predicts poor response and shortened survival. Combination of Lenalidomide and Dexamethasone (Len/Dex) in two large randomized trials demonstrated superior activity and outcomes in relapsed and refractory MM patients when compared to dexamethasone monotherapy. Here we report the efficacy (response rate RR and 6 mos event free survival EFS) of Lenalidomide in MM patients, according to their del13 and t(4;14) status. Methods: The MM016 trial is a multicenter single-arm open label expanded access program for Lenalidmide in previously treated MM. Pts received Dex 40 mg orally days 1–4, 9–12, 17–20 and Len 25 mg daily orally on days 1–21 of 28Day cycle. Beginning with cycle 5, Dex was reduced to 40 mg days 1–4 only. Fluorescence in situ hybridization (FISH) detected the presence or absence of deletion 13 and t(4;14) on interphase bone marrow aspirates obtained either at the time of initial diagnosis or relapse. Commercially available FISH probes were used to detect of del13q (D13S15 and D13S319) and t(4;14)(p16;q32) (LSI FGFR3 and LSI IGH). EBMT/IBMTR criteria were used to define RR. EFS was defined as the time from initiation of treatment with Len/Dex to the first occurrence of disease relapse, progression, death from any cause as of the date of this analysis (July 4, 2006). Results: To date 36 patients were enrolled at our site: median age was 61 yrs (41–76), median time from diagnosis was 77.5 months (range: 19.5–3018) median β2 microglobulin 4.1 mg/dl (1.3–17.5), median number of prior treatments of 2 (2–4) with 11 patients (31%) previously treated with Thalidomide, 23 (64%) with Bortezomib and 44.5 % had ASCT. Del 13 and t(4;14) were detected in 16(44.5%) and 7(19.4%) patients respectively. 6/16 (37.5%) with del13 also had t(4;14) as opposed to only 1 patient (5%) in the no del13 group. The del13 vs no del13 groups were balanced with respect to major prognostic factors (age, albumin, DS stage, and lines of prior therapy); β2 microglobulin was higher in the del 13 group (median 5.2 vs 3.3). The overall response RR (CR+PR) to Len/Dex was 83%, 90% for the no del13 group and 75% in the del 13 group. At the time of this analysis 8 events (6 deaths, 2 relapses) have occurred (22%), 5 in the non del13 group. EFS estimates at 6 months were similar in the 2 groups [non del13: 73% vs 81% with del13; p=0.61]. The RR (CR+PR) for t(4;14) and non t(4;14) groups were also identical (71.5% and 86% respectively) with similar 6 mos EFS [71.4% vs. 72.4%; p=0.66]. EFS was also similar when results were analyzed according to age (< or > 65), prior transplant or prior thalidomide. Conclusion: Treatment with Lenalidomide with Dexamethasone may overcome the poor prognosis conferred by deletion 13 and/or t (4; 14) relative to event free survival and response rate. Updated results from a longer follow-up will be presented at the meeting.

Myeloablative conditioning with FLUBUP (fludarabine 50mg/m2 i.v. days -6 to -2 and busulfan 3.2mg/kg i.v. once daily days -5 to -2) is convenient to administer and relatively well tolerated. The addition of ATG (Thymoglobulin 4.5mg/kg over 3 days) to cyclosporine and short course methotrexate appears to decrease the incidence and severity of graft-versus-host disease (GVHD) but may contribute to a still unacceptable relapse rate when this regimen is used in AML. We have added low dose TBI (200cGy x 2 day -1 or 0) to our standard FLUBUP/ATG conditioning regimen in all patients with AML in an effort to enhance cytotoxicity and reduce relapse rate. 135 patients (pts) received allogeneic stem cell transplants at our centre between 07/99 and 05/05. Ninety pts (66.7%), transplanted between 07/99 and 04/04 received FLUBUP/ATG while the remaining 45 (33.3%) received FLUBUP/ATG+TBI. Patient age was 16–65, median 42, in the FLUBUP/ATG group and 20–63, median 46, in the group with additional TBI. 71.1% of pts receiving TBI were in CR1 or CR2 compared to 62.2% of those not receiving TBI (p=ns). The remainder had more advanced disease. The distribution into standard cytogenetic risk groups between the two groups was also not statistically significant. More pts received peripheral blood stem cells in the TBI group (73.3% vs. 91.1%, p=0.02). In the TBI group 17 pts (37.8%) received a matched related donor transplant as opposed to 50 (55.6%) in the non-TBI group. The others were transplanted from mismatched related or volunteer unrelated donors. There was no difference between the groups with respect to neutrophil and platelet engraftment, rates of severe acute GVHD (6.6% Grade III-IV in the TBI group vs 7.8% for the non-TBI group) or chronic GVHD (51.1% in the TBI group vs 50.0 in the non TBI group). At one year non-relapse mortality was 12.2% vs.16.7% (p=ns) and relapse was 37.8% vs.13.3% (p=0.003) in the groups with and without TBI respectively. Overall survival (OS) at one year was 82% (95% CI 68%-91%) in the TBI group versus 61% (95% CI 50%-70%) in the non-TBI group (p=0.015). After adjusting for risk group, donor type and patient age the Cox proportional hazards ratio was 0.41 (0.19–0.90) in favour of the addition of TBI. Pts receiving FLUBUP/ATG+TBI were therefore 60% less likely to die within the first year than those receiving FLUBUP/ATG. When OS was assessed including all available observation time the statistical difference by log-rank test persisted, p=0.0237. Relapse-free survival was also improved by the addition of TBI (80% (65%-89% vs. 50% (39%-60%), p=0.001). After adjusting for risk group, donor type, patient age as well as cytogenetic risk group the Cox proportional hazards ratio was 0.23 (0.11–.0.50) in favour of additional TBI suggesting that pts receiving TBI were about 77% less likely to die or relapse within the first year compared to pts who did not receive TBI. The addition of TBI was well tolerated and helped overcome the risk of relapse associated with increased immunosuppression from ATG.

Historically myeloablative hematopietic stem cell transplants (SCT) from donors other than genotypically identical siblings (MRD) have had worse outcomes when the same conditioning and GVHD prevention is used. It is important to know if this is still the case when all patients receive better tolerated regimens, using i.v. rather than oral busulfan for example, and more aggressive GVHD prophyaxis. We have compared outcomes of pateints (pts) receiving myeloablative fludarabine/busulfan based conditioning (FLUBUP) between 05/99 and 05/05 according to donor. All pts received fludarabine 50mg/m2 on days -6 to -2 and IV busulfan (Busulfex, PDL Pharma) at a myeloablative dose of 3.2 mg/kg daily days -5 to -2 inclusive +/− TBI 200cGy × 2 on day -1 or 0. Prophylaxis for GVHD was cyclosporine A, methotrexate with folinic acid and Thymoglobulin (Genzyme) 4.5 mg/kg in divided doses over 3 consecutive days pretransplant finishing D0. Patients were divided into four groups depending on donor - MRD, genotypically mismatched family members (MMRD), unrelated donors matched for HLA-A, -B, C, DR & DQ (MUD) and MMUD. Of 40 MMUD 32 were mismatched for one antigen, 7 for 2 and one for 3 at least at the allelic level. Baseline and transplant characteristics MRD MMRD MUD MMUD Number 201 22 81 40 Pt age (yrs) range/mean (SD) 18–66/45 (11.0) 19–63/44 (14.9) 16–61/40 (12.3) 19–64/40 (12.2) Donor age (yrs) range/mean (SD) 15–71/44 (11.1) 10–65/35 (19.1) 19–57/32 (8.5) 21–54/33 (8.2) Male pt % 63.7 54.6 58.0 65.0 Low risk (Acute leukemia CR1/2, CML CP1) % 41.8 54.6 55.6 32.5 TBI % (not risk factor for TRM) 23.9 31.8 42.0 47.5 Blood cell SCT % 87.6 90.9 43.2 65.0 Female to male SCT % 26.9 27.3 19.8 30.0 CMV+ve donor or recipient % 77.1 54.6 69.1 55.0 CD34+ cell dose/kg - range/median (IQR) 0.8–13.6/4.7(3.4–6.0) 2.0–10.3/4.1(3.3–6.9) 0.4–23.9/3.7(2.4–7.7) 0.9–17.7/5.0(3.0–7.0) Five-year survival (OS) estimates (95% CI) were MRD 60% (52%–67%), MMRD 58% (34%–75%), MUD 57% (45%–67%), MMUD 38% (23%–53%). By Cox regression analysis MRD, MMRD and MUD SCT had similar outcomes and were combined for a more robust analysis. The hazard ratio for OS for MMUD vs all others was 2.03 (95% CI 1.31–3.16, p = 0.002). After adjusting for gender, risk group, patient age (continuous), donor age (continuous), TBI, stem cell source, female donor to male recipient, CMV status and CD34+ cell dose (continuous) the hazard ratio was 1.69 (1.04–2.74) (p = 0.03). The cumulative incidence of relapse mortality was silmiar across all 4 groups, the difference in outcome was mostly attributable to TRM. Thus the cumulative incidence of TRM at 3 years was 31.6% (17.5%–46.7%) for MMUD vs 14.5% (10.8%–18.8%) for all others. We conclude that the FLUBUP protocol +/− TBI with Thymoglobulin gives comparable OS for recipients of SCT from all donors apart from MMUD and patients should be advised of the increased risk when the latter donors are the only ones available.