bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality Associated with Implantation and Management of Intrathecal Opioid Drug Infusion Systems to Treat Noncancer Pain
Authors: Coffey Robert J. , Owens Mary L. , Broste Steven K. , Dubois Michel Y. , Ferrante F Michael , Schultz David M. , Stearns Lisa J. , Turner Michael S. 
Published: September 2009

Background
In 2006, the authors observed a cluster of three deaths, which circumstances suggested were opioid-related, within 1 day after placement of intrathecal opioid pumps for noncancer pain. Further investigation suggested that mortality among such patients was higher than previously appreciated. The authors performed investigations to quantify that mortality and compare the results to control populations, including spinal cord stimulation and low back surgery.

Methods
After analyzing nine index cases--three sentinel cases and six identified by a prospective strategy--the authors used epidemiological methods to investigate whether mortality rates reflected patient- or therapy-related differences. Mortality rates after intrathecal opioid therapy and spinal cord stimulation were derived by correlating Medtronic device registration data with de-identified data from the Social Security Death Master File. Aggregate demographic and comorbidity data were obtained from Medicare and United Healthcare population databases to examine the influence of demographics and comorbidities on mortality.

Results
Device registration and Social Security analyses revealed an intrathecal opioid therapy mortality rate of 0.088% at 3 days after implantation, 0.39% at 1 month, and 3.89% at 1 yr-a higher mortality than after spinal cord stimulation implants or after lumbar diskectomy in community hospitals. Demographic, illness profile, and mortality analyses of large databases suggest, despite limitations, that excess mortality was related to intrathecal opioid therapy, and could not be fully explained by other factors. These findings were consistent with the nine index cases that revealed that respiratory arrest caused or contributed to death in all patients. No device malfunctions associated with overinfusion were identified among cases where data were available.

Conclusions
Patients with noncancer pain treated with intrathecal opioid therapy experience increased mortality compared to similar patients treated by using other therapies. Respiratory depression as a consequence of intrathecal drug overdosage or mixed intrathecal and systemic drug interactions is one plausible, but hypothetical mechanism. The exact causes for patient deaths and the proportion of those deaths attributable to intrathecal opioid therapy remain to be determined. These findings, although based on incomplete information, suggest that it may be possible to reduce mortality in noncancer intrathecal opioid therapy patients.
Operation Timing Does Not Affect Outcome after Coronary Artery Bypass Graft Surgery
Authors: Tan Paul J. , Xu Meng , Sessler Daniel I. , Bashour C Allen 
Published: September 2009

Background
Human factors such as fatigue, circadian rhythms, scheduling, and staffing may have an impact on patient care over the course of a day across all medical specialties. Research by the transportation industry concludes that human performance is degraded by shift work, circadian rhythm disturbances, and prolonged duty. This study investigated whether the timing of coronary artery bypass graft surgery affects outcomes.

Methods
The outcomes of coronary artery bypass graft surgery patients were analyzed according to the hour of the day, day of the workweek, month, and moon phase in which the surgery started. All patients who underwent isolated coronary artery bypass graft surgery between January 1, 1993 and July 1, 2006 were considered for the study.The primary outcome measurement was a compound morbidity outcome of six variables defined by the Society of Thoracic Surgeons. These outcomes included (1) in-hospital death, (2) acute postoperative myocardial infarction, (3) neurologic morbidity, including focal or global neurologic deficits or death without awakening, (4) serious infection morbidity consisting of sepsis syndrome or septic shock, (5) new-onset renal failure requiring dialysis, and (6) postoperative ventilatory support exceeding 72 h.

Results
The composite morbidity and in-hospital mortality rates were 4.8% and 1.4%, respectively. The number of cases each weekday, each month of the year, and during each phase of the moon were consistent. None of the time factors significantly affected the composite morbidity outcome.

Conclusions
Elective coronary artery bypass graft surgery can be scheduled throughout the workday, any day of the work week and in any month of the year without compromising outcome.
Effect of β-blocker Prescription on the Incidence of Postoperative Myocardial Infarction after Hip and Knee Arthroplasty
Authors: van Klei Wilton A. , Bryson Gregory L. , Yang Homer , Forster Alan J. 
Published: September 2009

Background
American College of Cardiology/American Heart Association guidelines recommend beta-blockade for selected low- and intermediate-risk noncardiac surgery patients. The authors evaluated the effect of perioperative beta-blockade on postoperative myocardial infarction (POMI) in low-risk patients undergoing intermediate-risk surgery.

Methods
Patients who underwent elective hip or knee arthroplasty between January 1, 2002 and June 30, 2006 were identified. POMI was defined as a Troponin T value of more than 0.1 ng . ml(-1). Patients were divided into three groups: those prescribed a beta-blocker on the day of surgery and throughout their hospital stay (or 7 days, whichever came first), those prescribed a beta-blocker on the day of surgery but discontinued during the first 7 days, and those not prescribed a beta-blocker on the day of surgery. Propensity analysis and logistic regression were used to determine the independent association of beta-blocker exposure on POMI.

Results
Of the 5,158 arthroplasty patients, 992 (18%) were treated with beta-blockers on the day of surgery. This beta-blocker was discontinued in 252 patients (25%). POMI occurred in 77 patients (1.5%). Discontinuation of beta-blocker prescription was significantly associated with POMI (odds ratio 2.0; 95% CI 1.1-3.9) and death (odds ratio 2.0; 95% CI 1.0-3.9).

Conclusion
After adjustment for confounders, discontinuation of beta-blocker prescription during the first week after surgery was significantly associated with POMI and death. These findings confirm the American College of Cardiology/American Heart Association Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery, which recommend not to withdraw beta-blocker therapy.
Mechanical Ventilation Induces a Toll/Interleukin-1 Receptor Domain-containing Adapter-inducing Interferon β–dependent Inflammatory Response in Healthy Mice
Authors: Vaneker Michiel , Heunks Leo M. A. , Joosten Leo A. , van Hees Hieronymus W. H. , Snijdelaar Dirk G. , Halbertsma Feico J. , van Egmond Jan , Netea Mihai G. , van der Hoeven Johannes G. , Scheffer Gert Jan 
Published: September 2009

Background
Mechanical ventilation (MV) can induce lung injury. Proinflammatory cytokines have been shown to play an important role in the development of ventilator-induced lung injury. Previously, the authors have shown a role for Toll-like receptor 4 signaling. The current study aims to investigate the role of Toll/interleukin-1 receptor domain-containing adapter-inducing interferon-beta (TRIF), a protein downstream of Toll-like receptors, in the development of the inflammatory response after MV in healthy mice.

Methods
Wild-type C57BL6 and TRIF mutant mice were mechanically ventilated for 4 h. Lung tissue and plasma was used to investigate changes in cytokine profile, leukocyte influx, and nuclear factor-kappaB activity. In addition, experiments were performed to assess the role of TRIF in changes in cardiopulmonary physiology after MV.

Results
MV significantly increased messenger RNA expression of interleukin (IL)-1beta in wild-type mice, but not in TRIF mutant mice. In lung homogenates, MV increased levels of IL-1alpha, IL-1beta, and keratinocyte-derived chemokine in wild-type mice. In contrast, in TRIF mutant mice, only a minor increase in IL-1beta and keratinocyte-derived chemokine was found after MV. Nuclear factor-kappaB activity after MV was significantly lower in TRIF mutant mice compared with wild-type mice. In plasma, MV increased levels of IL-6 and keratinocyte-derived chemokine. In TRIF mutant mice, no increase of IL-6 was found after MV, and the increase in keratinocyte-derived chemokine appeared less pronounced. TRIF deletion did not affect cardiopulmonary physiology after MV.

Conclusions
The current study supports a prominent role for TRIF in the development of the pulmonary and systemic inflammatory response after MV.
Tidal Volume Lower than 6 ml/kg Enhances Lung Protection
Authors: Terragni Pier Paolo , Del Sorbo Lorenzo , Mascia Luciana , Urbino Rosario , Martin Erica L. , Birocco Alberto , Faggiano Chiara , Quintel Michael , Gattinoni Luciano , Ranieri V Marco 
Published: September 2009

Background
Tidal hyperinflation may occur in patients with acute respiratory distress syndrome who are ventilated with a tidal volume (VT) of 6 ml/kg of predicted body weight develop a plateau pressure (PPLAT) of 28 < or = PPLAT < or = 30 cm H2O. The authors verified whether VT lower than 6 ml/kg may enhance lung protection and that consequent respiratory acidosis may be managed by extracorporeal carbon dioxide removal.

Methods
PPLAT, lung morphology computed tomography, and pulmonary inflammatory cytokines (bronchoalveolar lavage) were assessed in 32 patients ventilated with a VT of 6 ml/kg. Data are provided as mean +/- SD or median and interquartile (25th and 75th percentile) range. In patients with 28 < or = PPLAT < or = 30 cm H2O (n = 10), VT was reduced from 6.3 +/- 0.2 to 4.2 +/- 0.3 ml/kg, and PPLAT decreased from 29.1 +/- 1.2 to 25.0 +/- 1.2 cm H2O (P < 0.001); consequent respiratory acidosis (Paco2 from 48.4 +/- 8.7 to 73.6 +/- 11.1 mmHg and pH from 7.36 +/- 0.03 to 7.20 +/- 0.02; P < 0.001) was managed by extracorporeal carbon dioxide removal. Lung function, morphology, and pulmonary inflammatory cytokines were also assessed after 72 h.

Results
Extracorporeal assist normalized Paco2 (50.4 +/- 8.2 mmHg) and pH (7.32 +/- 0.03) and allowed use of VT lower than 6 ml/kg for 144 (84-168) h. The improvement of morphological markers of lung protection and the reduction of pulmonary cytokines concentration (P < 0.01) were observed after 72 h of ventilation with VT lower than 6 ml/kg. No patient-related complications were observed.

Conclusions
VT lower than 6 ml/Kg enhanced lung protection. Respiratory acidosis consequent to low VT ventilation was safely and efficiently managed by extracorporeal carbon dioxide removal.
Epidural Cooling Minimizes Spinal Cord Injury after Aortic Cross-clamping through Induction of Nitric Oxide Synthase
Authors: Ishikawa Akiko , Mori Atsuo , Kabei Nobuyuki , Yoshitake Akihiro , Suzuki Takeshi , Katori Nobuyuki , Morisaki Hiroshi , Yozu Ryohei , Takeda Junzo 
Published: September 2009

Background
By using a U-shaped lumen catheter, the authors examined the effects of epidural cooling on spinal cord injury after aortic cross-clamping (ACC), with a focus on changes of spinal cord blood flow and expression of inducible nitric oxide synthase.

Methods
Sixteen pigs were randomized into two groups: Control group (n = 8) or Cooling group (n = 8). In the latter, epidural cooling started at 30 min (baseline) before 45 min of ACC and persisted for the next 30 min of reperfusion period. Spinal cord blood flow and somatosensory-evoked potentials were assessed during peri-ACC period. At 48 h, we evaluated hind limb function by using Tarlov score and expression of inducible nitric oxide synthase on spinal cord using immunohistochemistry.

Results
After ACC, spinal cord blood flow dropped to a similar extent in both groups. During the reperfusion period, spinal cord blood flow increased up to 113% (103-124%), median (interquartile range), level transiently and decreased to 32% (22-47%) level versus baseline in the Control group, whereas it increased and remained at 92% (86-97%) level in the Cooling group. Simultaneously, somatosensory-evoked potentials showed that onset of loss time was delayed and recovery time was shortened in the Cooling group. Tarlov scores in the Cooling group were significantly higher and accompanied by normal-appearing motor neurons and significantly greater expression of inducible nitric oxide synthase on spinal cord versus the Control group.

Conclusions
This study shows that epidural cooling during ACC minimized the risk of spinal cord injury, possibly by preventing delayed hypoperfusion and upregulating inducible nitric oxide synthase expression.
A Population-based Analysis of Outpatient Colonoscopy in Adults Assisted by an Anesthesiologist
Authors: Alharbi Othman , Rabeneck Linda , Paszat Lawrence F. , Wijeysundera Duminda N. , Sutradhar Rinku , Yun Lingsong , Vinden Christopher M. , Tinmouth Jill 
Published: September 2009

Background
The use of propofol to sedate patients for colonoscopy, generally administered by an anesthesiologist in North America, is increasingly popular. In the United States, regional use of anesthesiologist-assisted endoscopy appears to correlate with local payor policy. This study's objective was to identify nonpayor factors (patient, physician, institution) associated with anesthesiologist assistance at colonoscopy.

Methods
The authors performed a population-based cross-sectional analysis using Ontario health administrative data, 1993-2005. All outpatient colonoscopies performed on adults were identified. Hierarchical multivariable modeling was used to identify patient (age, sex, income quintile, comorbidity), physician (specialty, colonoscopy volume), and institution (type, volume) factors associated with receipt of anesthesiologist-assisted colonoscopy.

Results
During the study period, 1,838,879 colonoscopies were performed on 1,202,548 patients. The proportion of anesthesiologist-assisted colonoscopies rose from 8.4% in 1993 to 19.1% in 2005 (P < 0.0001). In the hierarchical model, patients in low-volume community hospitals were five times more likely to receive anesthesiologist-assisted colonoscopy than patients in high-volume community hospitals (odds ration 4.9; 95% confidence interval 4.4-5.5). Less than 1% of colonoscopies in academic hospitals were anesthesiologist-assisted. Compared to gastroenterologists, surgeons were more likely to perform anesthesiologist-associated colonoscopy (odds ratio 1.7; 95% confidence interval 1.1-2.6).

Conclusions
In Ontario, rates of anesthesiologist-assisted colonoscopy have risen dramatically. Institution type was most strongly associated with this practice. Further investigation is needed to determine the most appropriate criteria for the use of anesthesiology services during colonoscopy.
Early Phase Pharmacokinetics but Not Pharmacodynamics Are Influenced by Propofol Infusion Rate
Authors: Masui Kenichi , Kira Marimo , Kazama Tomiei , Hagihira Satoshi , Mortier Eric P. , Struys Michel M. R. F. 
Published: September 2009

Background
Conventional compartmental pharmacokinetic models wrongly assume instantaneous drug mixing in the central compartment, resulting in a flawed prediction of drug disposition for the first minutes, and the flaw affects pharmacodynamic modeling. This study examined the influence of the administration rate and other covariates on early phase kinetics and dynamics of propofol by using the enlarged structural pharmacokinetic model.

Methods
Fifty patients were randomly assigned to one of five groups to receive 1.2 mg/kg propofol given with the rate of 10 to 160 mg . kg(-1). h(-1). Arterial blood samples were taken frequently, especially during the first minute. The authors compared four basic pharmacokinetic models by using presystemic compartments and the time shift of dosing, LAG time. They also examined a sigmoidal maximum possible drug effect pharmacodynamic model. Patient characteristics and dose rate were obtained to test the model structure.

Results
Our final pharmacokinetic model includes two conventional compartments enlarged with a LAG time and six presystemic compartments and includes following covariates: dose rate for transit rate constant, age for LAG time, and weight for central distribution volume. However, the equilibration rate constant between central and effect compartments was not influenced by infusion rate.

Conclusions
This study found that a combined pharmacokinetic-dynamic model consisting of a two-compartmental model with a LAG time and presystemic compartments and a sigmoidal maximum possible drug effect model accurately described the early phase pharmacology of propofol during infusion rate between 10 and 160 mg . kg(-1). h(-1). The infusion rate has an influence on kinetics, but not dynamics. Age was a covariate for LAG time.
Response Surface Modeling of the Interaction between Propofol and Sevoflurane
Authors: Schumacher Peter M. , Dossche Jan , Mortier Eric P. , Luginbuehl Martin , Bouillon Thomas W. , Struys Michel M. R. F. 
Published: September 2009

Background
Propofol and sevoflurane display additivity for gamma-aminobutyric acid receptor activation, loss of consciousness, and tolerance of skin incision. Information about their interaction regarding electroencephalographic suppression is unavailable. This study examined this interaction as well as the interaction on the probability of tolerance of shake and shout and three noxious stimulations by using a response surface methodology.

Methods
Sixty patients preoperatively received different combined concentrations of propofol (0-12 microg/ml) and sevoflurane (0-3.5 vol.%) according to a crisscross design (274 concentration pairs, 3 to 6 per patient). After having reached pseudo-steady state, the authors recorded bispectral index, state and response entropy and the response to shake and shout, tetanic stimulation, laryngeal mask airway insertion, and laryngoscopy. For the analysis of the probability of tolerance by logistic regression, a Greco interaction model was used. For the separate analysis of bispectral index, state and response entropy suppression, a fractional Emax Greco model was used. All calculations were performed with NONMEM V (GloboMax LLC, Hanover, MD).

Results
Additivity was found for all endpoints, the Ce(50, PROP)/Ce(50, SEVO) for bispectral index suppression was 3.68 microg. ml(-1)/ 1.53 vol.%, for tolerance of shake and shout 2.34 microg . ml(-1)/ 1.03 vol.%, tetanic stimulation 5.34 microg . ml(-1)/ 2.11 vol.%, laryngeal mask airway insertion 5.92 microg. ml(-1) / 2.55 vol.%, and laryngoscopy 6.55 microg. ml(-1)/2.83 vol.%.

Conclusion
For both electroencephalographic suppression and tolerance to stimulation, the interaction of propofol and sevoflurane was identified as additive. The response surface data can be used for more rational dose finding in case of sequential and coadministration of propofol and sevoflurane.
Epitope mapping of canine distemper virus phosphoprotein by monoclonal antibodies
Authors: Sugai Akihiro , Kooriyama Takanori , Sato Hiroki , Yoneda Misako , Kai Chieko 
Published: September 2009

ABSTRACTThe gene for phosphoprotein (P) of CDV encodes three different proteins, P, V, and C. The P protein is involved in viral gene transcription and replication. In the present study, we produced MAbs against a unique domain of the CDV‐P protein, from aa 232 to 507, and determined their antigenic sites. By immunizing BALB/c mice with the recombinant P protein‐specific fragment, we obtained six MAbs. Competitive binding inhibition assays revealed that they recognized two distinct regions of the P protein. Western blot analysis and immunofluorescence assays using deletion mutants of the unique C‐terminus of the CDV‐P protein revealed that all MAbs recognized a central short region (aa 233–303) of the CDV‐P protein. In addition, linear and conformational epitopes have been determined, and at least four antigenic sites exist in the P protein central region. Furthermore, four of the MAbs were found to react with the P protein of recent Japanese field isolates but not with that of the older CDV strains, including a vaccine strain. Thus, these MAbs could be clinically useful for quick diagnosis during the CDV outbreaks.
Mudstone compaction curves in basin modelling: a study of Mesozoic and Cenozoic Sediments in the northern North Sea
Authors: Marcussen Ø. , Faleide J. I. , Jahren J. , Bjørlykke K. 
Published: September 2009

ABSTRACTBasin modelling studies are carried out in order to understand the basin evolution and palaeotemperature history of sedimentary basins. The results of basin modelling are sensitive to changes in the physical properties of the rocks in the sedimentary sequences. The rate of basin subsidence depends, to a large extent, on the density of the sedimentary column, which is largely dependent on the porosity and therefore on the rate of compaction. This study has tested the sensitivity of varying porosity/depth curves and related thermal conductivities for the Cenozoic succession along a cross‐section in the northern North Sea basin, offshore Norway. End‐member porosity/depth curves, assuming clay with smectite and kaolinite properties, are compared with a standard compaction curve for shale normally applied to the North Sea. Using these alternate relationships, basin geometries of the Cenozoic succession may vary up to 15% from those predicted using the standard compaction curve. Isostatic subsidence along the cross‐section varies 2.3–4.6% between the two end‐member cases. This leads to a 3–8% difference in tectonic subsidence, with maximum values in the basin centre. Owing to this, the estimated stretching factors vary up to 7.8%, which further gives rise to a maximum difference in heat flow of more than 8.5% in the basin centre. The modelled temperatures for an Upper Jurassic source rock show a deviation of more than 20 °C at present dependent on the thermal conductivity properties in the post‐rift succession. This will influence the modelled hydrocarbon generation history of the basin, which is an essential output from basin modelling analysis. Results from the northern North Sea have shown that varying compaction trends in sediments with varying thermal properties are important parameters to constrain when analysing sedimentary basins.