Robin High

Safety, efficacy, and cost-effectiveness of common laparoscopic procedures

BackgroundLaparoscopic surgery has been shown to offer superior surgical outcomes for most abdominal surgical procedures. However, there is hardly any evidence on surgical outcomes with patient risk stratification. This study aimed to compare outcomes of common laparoscopic and open surgical procedures for varying illness severity.MethodsA retrospective analysis of surgical outcomes for six commonly performed surgical procedures including cholecystectomy, appendectomy, reflux surgery, gastric bypass surgery, ventral hernia repair, and colectomy was performed using the University HealthSystem Consortium (UHC) Clinical Database/Resource Manager (CDB/RM). The 3-year discharge data for the six commonly performed laparoscopic surgical procedures were analyzed for outcome measures including observed mortality, overall patient morbidity, intensive care unit (ICU) admissions, 30-day readmissions, length of hospital stay, and hospital costs.ResultsIn this study, 208,314 patients underwent one of six common surgical procedures by either the open or the laparoscopic approach. Overall, the laparoscopic approach showed significantly lower mortality, reduced morbidity, fewer ICU admissions and 30-day readmissions, shorter hospital stay, and significantly reduced hospital costs for all the procedures. At stratification by illness severity, the laparoscopic group showed better or comparable surgical outcomes across all the illness severity groups. However, the observed mortality was comparable for the minor and moderate severity patients between laparoscopic and open surgery for most procedures. The 30-day readmission rate for major/extreme severity patients was comparable between the two groups for most surgical procedures.ConclusionsThis study demonstrated the superiority of laparoscopy over conventional open surgery across all illness severity risk groups for common surgical procedures. The results in general show that laparoscopic surgery is safe, efficacious, and cost-effective compared with open surgery and suggest that laparoscopic surgery should be the procedure of choice for all common surgical procedures, regardless of illness severity.

A theory-driven, longitudinal evaluation of the impact of team training on safety culture in 24 hospitals

Background Effective teamwork facilitates collective learning, which is integral to safety culture. There are no rigorous evaluations of the impact of team training on the four components of safety culture—reporting, just, flexible and learning cultures. We evaluated the impact of a year-long team training programme on safety culture in 24 hospitals using two theoretical frameworks. Methods We used two quasi-experimental designs: a cross-sectional comparison of hospital survey on patient safety culture (HSOPS) results from an intervention group of 24 hospitals to a static group of 13 hospitals and a pre-post comparison of HSOPS results within intervention hospitals. Dependent variables were HSOPS items representing the four components of safety culture; independent variables were derived from items added to the HSOPS that measured the extent of team training, learning and transfer. We used a generalised linear mixed model approach to account for the correlated nature of the data. Results 59% of 2137 respondents from the intervention group reported receiving team training. Intervention group HSOPS scores were significantly higher than static group scores in three dimensions assessing the flexible and learning components of safety culture. The distribution of the adoption of team behaviours (transfer) varied in the intervention group from 2.8% to 31.0%. Adoption of team behaviours was significantly associated with odds of an individual reacting more positively at reassessment than baseline to nine items reflecting all four components of safety culture. Conclusions Team training can result in transformational change in safety culture when the work environment supports the transfer of learning to new behaviour.

Cyclin-Dependent Kinase 5 Is Amplified and Overexpressed in Pancreatic Cancer and Activated by Mutant K-Ras

Purpose: To evaluate the nature of cyclin-dependent kinase 5 (CDK5) hyperactivity in pancreatic cancer progression. Experimental Design: We used genetic, biochemical, and molecular biology methods to investigate the nature and function of overexpression of CDK5 and its activators p35 and p39 during the progression of pancreatic cancer. Results: Amplification of the CDK5 gene or either of its main activators, p35 and p39, was observed in 67% of human pancreatic ductal adenocarcinoma (PDAC). CDK5, p35, and p39 were rarely expressed in pancreatic ducts whereas more than 90% of PDACs had increased levels of CDK5 and p35. Increased levels of CDK5, p35, and p39 protein were observed in several pancreatic cancer cell lines. Inhibition of CDK5 kinase activity using a CDK5 dominant-negative mutant or the drug roscovitine significantly decreased the migration and invasion of pancreatic cancer cells in vitro. Increased CDK5 kinase activity was also observed in immortalized human pancreatic nestin-expressing (HPNE) cells expressing a mutant form of K-Ras (G12D) compared with HPNE cells expressing native K-Ras. G12D K-Ras increased cleavage of p35 to p25, a stable and greater activator of CDK5, thus implicating a role for CDK5 in early progression of PDAC. Inhibition of the signaling cascade downstream of mutant K-Ras (G12D) that involves mitogen-activated protein/extracellular signal–regulated kinase, phosphoinositide 3-kinase, or CDK5 decreased p25 protein levels. Conclusion: These results suggest that mutant K-Ras acts in concert with CDK5 and its activators to increase malignant progression, migration, and invasion of pancreatic cancer cells. Clin Cancer Res; 17(19); 6140–50. ©2011 AACR.

Malfunction of the da Vinci Robotic System During Robot-Assisted Laparoscopic Prostatectomy: An International Survey

PURPOSE To determine how urologists manage technical malfunction of the Da Vinci robotic system during robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS A web-based survey was sent to urologists performing RARP. The survey questions were related to the stage of operation during which robotic malfunction occurred, management of malfunctions, and most common types of robotic malfunction. In addition, data were collected concerning surgical volume and training. RESULTS One hundred (56.8%) of the 176 responding surgeons had experienced an irrecoverable intraoperative malfunction. Eighty respondents experienced mechanical failure before starting RARP, of which 46 (57.5%) rescheduled, 15 (18.8%) performed an open radical approach, 12 (15%) performed standard laparoscopic prostatectomy, and 4 (4.9%) docked another robot. Sixty-three respondents experienced mechanical failure before starting urethrovesical anastomosis, of which 26 (41.2%) converted to an open procedure, 20 (31.7%) converted to standard laparoscopy, 10 (15.8%) finished with one less arm, and 3 (4.7%) aborted the procedure. Thirty-two respondents experienced malfunction before completion of the anastomosis, of which 20 (62.5%) converted to standard laparoscopy, while 12 (37.5%) converted to open surgery. Fellowship trained surgeons were more likely to complete the prostatectomy using standard laparoscopy (P = 0.05). No significant differences existed between surgeons performing a high volume or low volume of prostatectomies in regard to management of malfunctions. CONCLUSION Intraoperative breakdown of the Da Vinci robot is uncommon, but patients should be counseled preoperatively and a plan devised on how breakdown will be managed. Intracorporeal suturing skills allow conversion to a pure laparoscopic approach, if necessary. Consequently, standard laparoscopic suturing skills should remain in the residency curriculum.

Bone presence between the central peg's radial fins of a partially cemented pegged all poly glenoid component suggest few radiolucencies.

BACKGROUND Cement penetration problems and/or cement-induced bone necrosis may contribute to glenoid component failures. An all polyethylene component was developed that promotes biologic fixation between radial fins of its central peg and utilizes minimal cement fixation for its peripheral pegs, but it has little published data. We hypothesized better bone presence between the radial fins would be associated with less overall radiolucencies. This studys purpose was to utilize computed tomography (CT) and plain films to assess for bone between the central pegs radial fins and to assess overall component radiolucencies. MATERIALS AND METHODS Thirty-five of 48 consecutively performed total shoulder arthroplasties (TSA) for primary glenohumeral osteoarthritis were in patients able to participate a minimum 2 years after surgery. All had reamed humeral head bone packed between radial fins of the central peg and minimal cement for the peripheral pegs. Thin cut (0.625 mm) CT scans, standardized plain films, Simple Shoulder Tests (SST), and Constant scores were obtained. A musculoskeletal radiologist calculated Yian CT scores, bone presence between fins on CT, and Lazarus radiolucency scores. RESULTS At a mean of 43 months, by CT: 1) better Yian scores correlated with more bone between fins, and 2) bone was present in 6/6 inter-fin compartments in 23/35 shoulders, averaging 4.5/6 overall. Mean Lazarus radiolucency score was 0.45. Mean SST and Constant scores were 10.3 and 81.3, respectively. CONCLUSION TSA utilizing autologous bone in inter-fin compartments of the central peg and minimal peripheral peg cement maintained bone presence a minimum 2 years post-op. More bone imparted fewer overall component radiolucencies.

Issues in accelerometer methodology: the role of epoch length on estimates of physical activity and relationships with health outcomes in overweight, post-menopausal women

BackgroundCurrent accelerometer technology allows for data collection using brief time sampling intervals (i.e., epochs). The study aims were to examine the role of epoch length on physical activity estimates and subsequent relationships with clinically-meaningful health outcomes in post-menopausal women.MethodsData was obtained from the Woman On the Move through Activity and Nutrition Study (n = 102). Differences in activity estimates presented as 60s and 10s epochs were evaluated using paired t-tests. Relationships with health outcomes were examined using correlational and regression analyses to evaluate differences by epoch length.ResultsInactivity, moderate- and vigorous-intensity activity (MVPA) were significantly higher and light-intensity activity was significantly lower (all P < 0.001) when presented as 10s epochs. The correlation between inactivity and self-reported physical activity was stronger with 10s estimates (P < 0.03); however, the regression slopes were not significantly different. Conversely, relationships between MVPA and body weight, BMI, whole body and trunk lean and fat mass, and femoral neck bone mineral density was stronger with 60s estimates (all P < 0.05); however, regression slopes were similar.ConclusionThese findings suggest that although the use of a shorter time sampling interval may suggestively reduce misclassification error of physical activity estimates, associations with health outcomes did not yield strikingly different results. Additional studies are needed to further our understanding of the ways in which epoch length contributes to the ascertainment of physical activity in research studies.Trial RegistrationClinical Trials Identifier: NCT00023543

Girls on the Run: A Quasi-Experimental Evaluation of a Developmentally Focused Youth Sport Program

BACKGROUND Evidence supporting the effectiveness of a developmental-focused youth sport (DYS) program designed exclusively for elementary school aged girls is mounting. The purpose of this study was to evaluate the impact of on the Girls on the Run program on psychological and physical assets among 3rd- to 5th-grade girls. METHODS A longitudinal quasi-experimental study was conducted to evaluate intervention effects among 877 participants categorized into 1 of 3 groups (never, newly, and previously exposed). A 64-item self-report survey measured developmental assets at 3 time-points. Nested random effects ANOVA models were used to compare demographic factors and psychological and physical assets between exposure groups and to compare longitudinal differences in these assets. RESULTS After adjustment for multiple comparisons, previous program participants had significantly higher physical activity commitment (P = .006) and physical activity levels (P = .047) at preintervention than never exposed. From pre- to postintervention body image improved in newly exposed participants (P = .03). Physical activity increased from preintervention to follow-up among never and newly exposed participants (all P < .05). CONCLUSIONS Although we were unable to fully confirm the study hypotheses, the results of the current study provide new evidence to support future long-term studies examining the effectiveness of an innovative DYS program for 3rd- to 5th-grade girls.

Outcomes Following Distal Humeral Fracture Fixation with an Extensor Mechanism-On Approach

BACKGROUND Distal humeral fractures have traditionally been managed with surgical approaches that disrupt the extensor mechanism. We hypothesized that an extensor mechanism-on approach for operative fixation of distal humeral fractures with parallel or orthogonal plate constructs would allow excellent healing, a motion arc of the elbow exceeding 100°, and maintenance of extensor mechanism strength. METHODS Distal humeral open reduction and internal fixation (ORIF) was performed with either orthogonal or parallel plate constructs in seventy-nine elbows. Thirty-seven elbows were fixed via an extensor mechanism-on surgical approach, and twenty-four of them were available for additional evaluation. Radiographs as well as MEPI (Mayo Elbow Performance Index), DASH (Disabilities of the Arm, Shoulder and Hand), and SF-36 (Short Form-36) scores were obtained. RESULTS All thirty-seven fractures healed primarily. Three elbows underwent later release because of stiffness. The median arc of elbow motion was 126° (range, 60° to 141°). The mean MEPI was 91.5 points and the mean DASH score was 15.9 points, indicating excellent scores with mild impairment. The median percent loss of triceps strength was 10% (range, 0% to 49%) compared with the contralateral, normal elbow. CONCLUSIONS Open treatment of distal humeral fractures with an extensor mechanism-on approach results in excellent healing, a mean elbow flexion-extension arc exceeding 100°, and maintenance of 90% of elbow extension strength compared with that of the contralateral, normal elbow.

Rapid Detection of Coronary Artery Stenoses With Real-Time Perfusion Echocardiography During Regadenoson Stress

Background— Real-time myocardial contrast echocardiography permits the detection of myocardial perfusion abnormalities during stress echocardiography, which may improve the accuracy of the test in detecting coronary artery stenoses. We hypothesized that this technique could be used after a bolus injection of the selective A2A receptor agonist regadenoson to rapidly and safely detect coronary artery stenoses. Methods and Results— In 100 patients referred for quantitative coronary angiography, real-time myocardial contrast echocardiography was performed during a continuous intravenous infusion of 3% Definity at baseline and at 2-minute intervals for up to 6 minutes after a regadenoson bolus injection (400 &mgr;g). Myocardial perfusion was assessed by examination of myocardial contrast replenishment after brief high mechanical index impulses. A perfusion defect was defined as a delay (>2 seconds) in myocardial contrast replenishment in 2 contiguous segments. Wall motion was also analyzed. The overall sensitivity/specificity/accuracy for myocardial perfusion analysis in detecting a >50% diameter stenosis was 80%/74%/78%, whereas for wall motion analysis it was 60%/72%/66% (P<0.001 for differences in sensitivity). Sensitivity for myocardial perfusion analysis was highest on images obtained during the first 2 minutes after regadenoson bolus (P<0.001 compared with wall motion), whereas wall motion sensitivity was highest at the 4-to-6–minute period after the bolus. No significant side effects occurred after regadenoson bolus injection. Conclusions— Regadenoson real-time myocardial contrast echocardiography appears to be a feasible, safe, and rapid noninvasive method for the detection of significant coronary artery stenoses. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT0087369.

Combinatorial assessments of brain tissue metabolomics and histopathology in rodent models of human immunodeficiency virus infection

Metabolites are biomarkers for a broad range of central nervous system disorders serving as molecular drivers and byproducts of disease pathobiology. However, despite their importance, routine measures of brain tissue metabolomics are not readily available based on the requirements of rapid tissue preservation. They require preservation by microwave irradiation, rapid freezing or other methods designed to reduce post mortem metabolism. Our research on human immunodeficiency virus type one (HIV-1) infection has highlighted immediate needs to better link histology to neural metabolites. To this end, we investigated such needs in well-studied rodent models. First, the dynamics of brain metabolism during ex vivo tissue preparation was shown by proton magnetic resonance spectroscopy in normal mice. Second, tissue preservation methodologies were assessed using liquid chromatography tandem mass spectrometry and immunohistology to measure metabolites and neural antigens. Third, these methods were applied to two animal models. In the first, immunodeficient mice reconstituted with human peripheral blood lymphocytes then acutely infected with HIV-1. In the second, NOD scid IL2 receptor gamma chain knockout mice were humanized with CD34+ human hematopoietic stem cells and chronically infected with HIV-1. Replicate infected animals were treated with nanoformulated antiretroviral therapy (nanoART). Results from chronic infection showed that microgliosis was associated with increased myoinostitol, choline, phosphocholine concentrations and with decreased creatine concentrations. These changes were partially reversed with nanoART. Metabolite responses were contingent on the animal model. Taken together, these studies integrate brain metabolomics with histopathology towards uncovering putative biomarkers for neuroAIDS.