Does a first-case on-time-start initiative achieve its goal by starting the entire process earlier or by tightening the distribution of start times?

BACKGROUND: We explored whether a previously successful initiative to improve first-case on-time starts succeeded because (i) preoperative steps started earlier (but the process did not necessarily improve) or (ii) the process was brought into better control. METHODS: We analysed 35 months of data comprising 28 882 first cases to calculate the difference of the time a patient entered the operating room (OR) vs the scheduled entry time. Median and inter-quartile range were used to evaluate changes in distribution parameters. A statistical process-control methodology was used to compare the differences in performance between the pre- and post-intervention phases. RESULTS: Post-intervention first cases entered the OR on average within 4 min [95% confidence interval (CI): 4-5 min] of the scheduled start time, as opposed to within 8 min (95% CI: 8-8 min) in the pre-intervention period. The median delay decreased from 5 min (95% CI: 5-5 min) to 2 min (95% CI: 2-2 min). The inter-quartile range of the difference between the scheduled start time and the first case in room time decreased from 13 min (95% CI: 13-13 min) to 10 min (95% CI: 9-10 min). CONCLUSIONS: The reduction in inter-quartile range demonstrates that improvement in on-time starts resulted from the process being in better control. The start time of preoperative preparatory activities did not move earlier, which means that OR and preoperative staff do not need to arrive at work earlier. Improvements resulting from the process being in control were sustained.

13-Year experience in external fixation of the pelvis: complications, reduction and removal.

PURPOSE: To evaluate the complications associated with anterior pelvic external fixation and the success of this device in maintaining reduction when used in conjunction with sacroiliac screws. METHODS: Through a retrospective clinical study at an academic Level I Trauma Center, 129 patients fit the criteria for inclusion with a mean duration of anterior pelvic external fixation of 62 days and mean follow-up of 360 days. Charts were reviewed for complications postoperatively. The symphysis diastasis, vertical displacement and posterior displacement of each hemipelvis were quantified from pelvic radiographs. RESULTS: Of the 129 patients receiving anterior pelvic external fixation, 14 (10.9 %) presented to an emergency department for problems with their anterior pelvic external fixation. Of these 14 patients, 7 (5.4 %) required readmission, all for infectious concerns necessitating IV antibiotics. 6 (4.7 %) required formal operative debridement and device removal. 13 patients (10.1 %) had superficial pin site infections successfully treated with oral antibiotics. Reduction was maintained (rated as fair, good or excellent) in all patients with radiographic follow-up (n = 74, average radiographic follow-up of 216 days) following removal of their anterior pelvic external fixation. 38 patients (30.4 %) had their anterior pelvic external fixation removed in clinic, while 87 (69.6 %) had formal removal in the operating room. CONCLUSION: While previous data suggest high complication rates in definitive anterior pelvic external fixation, we present the largest cohort of patients receiving anterior pelvic external fixation and sacroiliac screws, demonstrating a low complication rate while maintaining reduction of the pelvic ring. In addition, we found that these devices could be reliably removed in a clinic setting.

Open distal tibial shaft fractures: a retrospective comparison of medial plate versus nail fixation.

PURPOSE: Studies comparing open reduction internal fixation (ORIF) vs. intramedullary nailing (IMN) for distal tibia shaft fractures focus upon closed injuries containing small patient series with open fractures. As such, complication rates for open fractures are unknown. To characterize complications associated with ORIF vs. IMN, we compared complications based on surgical approach in a large patient series of open distal tibia shaft fractures. METHODS: Through retrospective analysis at an urban level I trauma center, 180 IMN and 36 ORIF patients with open distal tibia fractures from 2002 to 2012 were evaluated. Patient charts were reviewed to identify patient demographics, fracture grade (G), patient comorbidities, and postoperative complications including nonunion, malunion, infection, hardware-related pain, and wound dehiscence. Fisher's exact tests compared complications between ORIF and IMN groups. Multivariate regression identified risk factors with statistical significance for the development of a postoperative complication. RESULTS: One hundred and eighty IMN (G1 22, G2 79, and G3 79) and 36 ORIF (G1 10, G2 16, and G3 10) patients were included for analysis. ORIF patients had a higher rate of nonunion (25.0 %, n = 9) compared with IMN patients (10.6 %, n = 20, p = 0.03). No additional complication had a significant statistical difference between groups. Multivariable analysis shows only surgical method influenced the development of complications: ORIF patients had 2.52 greater odds of developing complications compared with IMN patients (95 % CI 1.05-6.02; p = 0.04). CONCLUSIONS: ORIF leads to higher rates of nonunion and significantly increases the odds of developing a complication compared with IMN for open distal tibia fractures. This is the first study investigating complication rates based on surgical approach in a large cohort of patients with exclusively open distal tibia fractures.

Variability in practice and factors predictive of total crystalloid administration during abdominal surgery: retrospective two-centre analysis.

BACKGROUND: Variation in clinical practice in the perioperative environment and intensive care unit is a major challenge facing modern medicine. The objective of the present study was to analyse intraoperative crystalloid administration practices at two academic medical centres in the USA. METHODS: We extracted clinical data from patients undergoing intra-abdominal procedures performed at UC Irvine (UCI) and Vanderbilt University (VU) Medical Centres. Limiting data to uncomplicated elective surgery with minimal blood loss, we quantified variability in fluid administration within individual providers, between providers, and between types of procedures using a corrected coefficient of variation (cCOV). Regression was performed using a general linear model to determine factors most predictive of fluid administration. RESULTS: For provider analysis and model building, 1327 UCI and 4585 VU patients were used. The average corrected crystalloid infusion rate across all providers at both institutions was 7.1 (sd 4.9) ml kg(-1) h(-1), an overall cCOV of 70%. Individual providers ranged from 2.3 (sd 3.7) to 14 (sd 10) ml kg(-1) h(-1). The final regression model strongly favoured personnel as predictors over other patient predictors. CONCLUSIONS: Wide variability in crystalloid administration was observed both within and between individual anaesthesia providers, which might contribute to variability in surgical outcomes.

Using Visual Analytics to Determine the Utilization of Preoperative Anesthesia Assessments.

BACKGROUND: Preoperative assessments are a required and essential element of anesthetic care, yet little is known about the utilization of these documents by clinicians who are not part of the anesthesia care team. As part of perioperative workflow restructuring, we implemented a data visualization technique of electronic medical record audit log data to understand the utilization of preoperative anesthesia assessments by non-anesthesia personnel. METHODS: An audit log cache containing 140 days of data was queried for all accesses of preoperative anesthesia assessment documents for any patient who had a preoperative anesthesia assessment that was accessed during that period. User roles were aggregated into categories. Descriptive statistics and data visualization were generated using R (R Software Foundation, Vienna, Austria). Comparisons were performed with the Wilcoxon signed rank test with continuity correction. RESULTS: During the study period, 73 802 (0.015%) of the 485 062 902 audit log accesses were preoperative anesthesia assessments representing 412 departments, 302 user roles, and 3 916 distinct users who accessed preoperative anesthesia assessments from 14 235 surgical cases. Each assessment was accessed 2.9 times on average. Assessments performed in the preoperative anesthesia assessment clinic were accessed more frequently than those created on the day of surgery in the preoperative holding room (3.58 ± 5.18 v. 1.98 ± 1.76 average views; p<0.0001). We observed accesses of these documents by pathology and general surgery researchers, as well as orthopedics attending physicians accessing documents that were two years old. CONCLUSIONS: This approach revealed patterns of utilization that had not been previously identified, including usage by surgical residents, surgical faculty, and pathology researchers both before and after the surgical event for which the documents are generated. Knowledge of these dependencies directly informed perioperative workflow restructuring efforts. This visual analytic approach could be broadly utilized to understand documentation dependencies in a variety of clinical contexts.

Safety of midazolam for sedation of HIV-positive patients undergoing colonoscopy.

OBJECTIVES: Because of concerns regarding interactions between midazolam and antiretroviral therapy (ART), alternative sedatives are sometimes used during procedural sedation. Our objective was to compare outcomes in patients on ART who received intravenous (iv) midazolam vs. iv diazepam, a second-line agent, during colonoscopy. METHODS: We conducted a retrospective analysis of adult HIV-positive patients who underwent colonoscopy over a 3.5-year period. Primary outcomes were sedation duration, nadir systolic blood pressure (SBP), nadir oxygen saturation, abnormal cardiac rhythm, and change in level of consciousness using a standardized scale. We calculated rates of adverse events according to benzodiazepine use and identified risk factors for complications using univariate and multivariate analyses. RESULTS: We identified 136 patients for this analysis: 70 received midazolam-based sedation and 66 received a diazepam-based regimen. There were no significant differences between the two groups with respect to sedation duration (mean 48.0 vs. 45.7 minutes for the midazolam and diazepam groups, respectively; P = 0.68), nadir SBP (mean 97.0 vs. 101.6 mmHg; P = 0.06), nadir oxygen saturation (mean 94.6 vs. 94.8%; P = 0.72) or rate of abnormal cardiac rhythm (11.4 vs. 19.7%; P = 0.18). More patients in the midazolam group experienced a depressed level of consciousness (91% vs. 74% in the diazepam group; P = 0.0075), but no patient required reversal of sedation or became unresponsive. CONCLUSIONS: We did not find evidence that patients who received midazolam for procedural sedation had clinical outcomes statistically different from those who received diazepam. These findings should be confirmed in prospective studies or in a randomized controlled trial.

Modulation of calcium-dependent chloride secretion by basolateral SK4-like channels in a human bronchial cell line.

The human bronchial cell line16HBE14o- was used as a model of airway epithelial cells to study the Ca(2+)-dependent Cl(-) secretion and the identity of K(Ca) channels involved in the generation of a favorable driving force for Cl(-) exit. After ionomycin application, a calcium-activated short-circuit current ( I(sc)) developed, presenting a transient peak followed by a plateau phase. Both phases were inhibited to different degrees by NFA, glybenclamide and NPPB but DIDS was only effective on the peak phase. (86)Rb effluxes through both apical and basolateral membranes were stimulated by calcium, blocked by charybdotoxin, clotrimazole and TPA. 1-EBIO, a SK-channel opener, stimulated (86)Rb effluxes. Block of basolateral K(Ca) channels resulted in I(sc) inhibition but, while reduced, I(sc) was still observed if mucosal Cl(-) was lowered. Among SK family members, only SK4 and SK1 mRNAs were detected by RT-PCR. KCNQ1 mRNAs were also identified, but involvement of K(cAMP) channels in Cl(-) secretion was unlikely, since cAMP application had no effect on (86)Rb effluxes. Moreover, chromanol 293B or clofilium, specific inhibitors of KCNQ1 channels, had no effect on cAMP-dependent I(sc). In conclusion, two distinct components of Cl(-) secretion were identified by a pharmacological approach after a Cai2+ rise. K(Ca) channels presenting the pharmacology of SK4 channels are present on both apical and basolateral membranes, but it is the basolateral SK4-like channels that play a major role in calcium-dependent chloride secretion in 16HBE14o- cells.

Characterization of the taurine transport pathway in A6 kidney cells.

We investigated the role of taurine in cell homeostasis and characterized the taurine transport pathway in cultured kidney cells (A6). The taurine concentration in A6 cells varies with the osmolarity of the culture medium, suggesting that taurine participates in cell osmolarity. Under isosmotic conditions, 14C-taurine efflux through the apical membranes (aJtaur) was 6-7 times lower than that through the basolateral membranes (bJtaur). Under hyposmotic conditions, aJtaur remained almost unchanged. On the contrary, bJtaur increased 8 times in comparison with isosmotic conditions. In hyposmotic conditions, bJtaur was inhibited by 500 microM DIDS, 50 microM NPPB, 10 microM of the two oxonol derivatives DISBAC(2)3 and WW-791, and 100 microM ketoconazole. Conversely, 100 microM 1,9-dideoxyforskolin, 10 microM tamoxifen, 100 microM niflumic acid and 50 microM verapamil had no inhibitory effects. Cell volume regulation upon hyposmotic stress was also found to be inhibited by DISBAC(2)3 (K0.5 of 5+/-1 microM) and by ketoconazole. Nystatin was used to permeabilize the apical membranes with the aim to further characterize bJtaur. 14C-taurine transepithelial fluxes in nystatin-treated cells were found to be linear over taurine concentrations ranging from 3.5 microM to 35 mM. Clamping the transepithelial voltage at positive values (serosal side) slightly stimulated the 14C-taurine transport. Similar time courses of 14C-taurine, 36Cl and 86Rb transepithelial fluxes were found under osmotic stimulation followed by DIDS inhibition in nystatin-treated cells. In whole cell patch-clamp experiments, DISBAC(2)3 application resulted in a strong and reversible decrease of the global Cl- current which was stimulated by hyposmotic stress. Our study indicates that taurine participates in the control of A6 cell osmolarity and that the transporting taurine pathway (efflux) is on the basolateral membranes. In addition to usual chloride channel blockers, oxonol was found to be a potent blocker of the taurine transport and of the swelling-activated chloride current. Using a pharmacological approach, we could not distinguish between a common or different pathway for Cl- and taurine.

Cloning and characterisation of amphibian ClC-3 and ClC-5 chloride channels.

Amphibians have provided important model systems to study transepithelial transport, acid-base balance and cell volume regulation. Several families of chloride channels and transporters are involved in these functions. The purpose of this review is to report briefly on some of the characteristics of the chloride channels so far reported in amphibian epithelia, and to focus on recently cloned members of the ClC family and their possible physiological roles. The electrophysiological characterisation, distribution, localisation and possible functions are reviewed and compared to their mammalian orthologs.

Tissue-specific N-glycosylation of the ClC-3 chloride channel.

A commercially available polyclonal antibody against a rClC-3/GST fusion protein was used in order to investigate the tissue distribution of the ClC-3 chloride channel protein. The antibody appeared to be specific to rClC-3 since no cross-reaction could be observed with rClC-4 or rClC-5 proteins when overexpressed in Xenopus oocytes. In mouse, mClC-3 was preferentially expressed in the central nervous system, intestine, and kidney. To a lower extent, mClC-3 protein was also detected in liver, lung, skeletal muscle, and heart. Surprisingly, the electrophoretic mobility of mClC-3 differed in the various tissues. After enzymatic digestion of N-linked oligosaccharide residues of membrane proteins from brain, intestine, and kidney, mClC-3 was found to migrate at its calculated molecular mass. This study provides important information regarding the specificity of the used antibody, indicates that ClC-3 is widely expressed in mouse, and that mClC-3 undergoes differential tissue-specific N-glycosylation.

Animal plasma membrane energization by proton-motive V-ATPases.

Proton-translocating, vacuolar-type ATPases, well known energizers of eukaryotic, vacuolar membranes, now emerge as energizers of many plasma membranes. Just as Na(+) gradients, imposed by Na(+)/K(+) ATPases, energize basolateral plasma membranes of epithelia, so voltage gradients, imposed by H(+) V-ATPases, energize apical plasma membranes. The energized membranes acidify or alkalinize compartments, absorb or secrete ions and fluids, and underwrite cellular homeostasis. V-ATPases acidify extracellular spaces of single cells such as phagocytes and osteoclasts and of polarized epithelia, such as vertebrate kidney and epididymis. They alkalinize extracellular spaces of lepidopteran midgut. V-ATPases energize fluid secretion by insect Malpighian tubules and fluid absorption by insect oocytes. They hyperpolarize external plasma membranes for Na(+) uptake by amphibian skin and fish gills. Indeed, it is likely that ion uptake by osmotically active membranes of all fresh water organisms is energized by V-ATPases. Awareness of plasma membrane energization by V-ATPases provides new perspectives for basic science and presents new opportunities for medicine and agriculture.

Control of apical membrane chloride permeability in the renal A6 cell line by nucleotides.

1. The effect of extracellular nucleotides applied on the apical side of polarised A6 cells grown on permeant filters was investigated by measuring the changes in (i) the 36Cl efflux through the apical membranes, (ii) the intracellular chloride concentrations (aCli, measured with N-(6-methoxyquinolyl) acetoethyl ester, MQAE), (iii) ICl, the short-circuit current in the absence of Na+ transport and (iv) the characteristics of the apical chloride channels using a patch-clamp approach. 2. ATP or UTP (0.1-500 microM) transiently stimulated ICl. The sequence of purinergic agonist potencies was UTP = ATP > ADP >> the P2X-selective agonist beta,gamma-methylene ATP = the P2Y-selective agonist 2-methylthioATP. Suramin (100 microM) as the P2Y antagonist Reactive Blue 2 (10 microM) had no effect on the UTP (or ATP)-stimulated current. These findings are consistent with the presence of P2Y2-like receptors located on the apical membranes of A6 cells. Apical application of adenosine also transiently increased ICl. This effect was blocked by theophylline while the UTP-stimulated ICl was not. The existence of a second receptor, of the P1 type is proposed. 3. ATP (or UTP)-stimulated ICl was blocked by apical application of 200 microM N-phenylanthranilic acid (DPC) or 100 microM niflumic acid while 100 microM glibenclamide was ineffective. 4. Ionomycin and thapsigargin both transiently stimulated ICl; the nucleotide stimulation of ICl was not suppressed by pre-treatment with these agents. Chlorpromazin (50 microM), a Ca2+-calmodulin inhibitor strongly inhibited the stimulation of ICl induced either by apical UTP or by ionomycin application. BAPTA-AM pre-treatment of A6 cells blocked the UTP-stimulated ICl. Niflumic acid also blocked the ionomycin stimulated ICl. 5. A fourfold increase in 36Cl effluxes through the apical membranes was observed after ATP or UTP application. These increases of the apical chloride permeability could also be observed when following aCli changes. Apical application of DPC (1 mM) or 5-nitro-2(3-phenylpropylamino)benzoic acid (NPPB; 500 microM) produced an incomplete inhibition of 36Cl effluxes through the apical membranes in ATP-stimulated and in untreated monolayers. 6. In single channel patch-clamp experiments, an apical chloride channel with a unitary single channel conductance of 7.3 +/- 0.6 pS (n = 12) was usually observed. ATP application induced the activation of one or more of these channels within a few minutes. 7. These results indicate that multiple purinergic receptor subtypes are present in the apical membranes of A6 cells and that nucleotides can act as modulators of Cl- secretion in renal cells.

Regulation of Cl- secretion in seawater fish (Dicentrarchus labrax) gill respiratory cells in primary culture.

1. Primary cultures of sea bass (Dicentrarchus labrax) gill cells grown on permeable membranes form a highly differentiated tight epithelium composed of respiratory-like cells. This preparation was also found to provide a functional model for investigating the hormonal regulation of Cl- secretion. 2. In control conditions, i.e. in the absence of hormones or other stimuli, the cultured epithelium showed a short-circuit current (Isc) of 8.8 +/- 0.4 microA cm-2, a transepithelial potential (Vt) of 28.6 +/- 0.6 mV (serosal side positive), and a transepithelial resistance (Rt) of 5026 +/- 127 Omega cm2. Addition of 50 nM PGE2 caused a stimulation of Isc, Vt and transepithelial conductance, Gt. The increase in Isc was probably due to the elevation in Cl- secretion, since it could be correlated with the stimulation of serosal to mucosal 36Cl- flux. Application of the neurohypophyseal peptide arginine vasotocin (AVT; 50 nM) or the beta-adrenergic agonist isoproterenol (isoprenaline; 0. 5 microM) evoked a stimulation in Cl- secretion, as was shown by the increases in Isc and Gt. The excitatory effect of isoproterenol followed by the inhibitory action of propranolol, a beta-adrenergic antagonist, suggested the presence of beta-adrenergic receptors. Noradrenaline (0.1 microM) elicited a reduction in Isc, Vt and Gt, which was counterbalanced by the addition of phentolamine, an alpha-adrenergic antagonist. This suggested an activation of alpha-adrenergic receptors. 3. This study provides evidence for hormonal control of the Cl- secretion in sea bass gill respiratory cells in culture, involving AVT, prostaglandin (PGE2), and beta- and alpha-adrenergic receptors.

Characterization of the putative chloride channel xClC-5 expressed in Xenopus laevis oocytes and comparison with endogenous chloride currents.

1. We recently cloned a putative chloride channel (xClC-5) from the renal cell line A6, which induced the appearance of a Cl- conductance not found in control oocytes after homologous expression in Xenopus oocytes. With the aim of increasing the Xenopus oocyte xClC-5 expression, we constructed a new plasmid in which the native 5' and 3' non-coding regions of xClC-5 were replaced by the non-coding regions of the Xenopus beta-globin sequence and in which a Kozak consensus site was introduced before the initiator ATG. 2. We then compared the induced currents Inative (induced by injection of cRNA presenting the native non-coding regions of xClC-5) and Ibeta-globin (induced by injection of cRNA presenting the non-coding regions of the Xenopus beta-globin sequence) investigating anion selectivity and anion blocker sensitivity. Several differences were found: (1) expression yield and oocyte surviving rate were largely increased by injecting (beta) xClC-5 cRNA, (2) the Ibeta-globin outward rectification score was 2.6 times that of Inative, (3) the anion conductivity sequence was nitrate > bromide > chloride > iodide >> gluconate for Ibeta-globin and iodide > bromide > nitrate > chloride >> gluconate for Inative, (4) 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), anthracene-9-carboxylic acid (9-AC), DIDS, lanthanum ions, cAMP and ionomycin-induced [Ca2+]i increase inhibited Inative but had no effect on Ibeta-globin, and (5) Inative showed considerable similarity to the previously reported endogenous current appearing after ClC-6 or pICln cRNA injection. 3. Comparison of Inative with the endogenous chloride current ICl,swell which develops under hyposmotic conditions demonstrated several similarities in their electrophysiological and pharmacological characteristics but were nevertheless distinguishable. 4. In vitro translation assays demonstrated that protein synthesis was much greater using the (beta) xClC-5 construct than that of xClC-5. Furthermore, immunoreactivity of membrane preparations of Xenopus oocytes was only observed with the (beta) xClC-5 construct, its intensity being positively correlated with Ibeta-globin levels. 5. In addition, the current induced in (beta) xClC-5 cRNA-injected oocytes presented a very marked pH dependence (inhibition by acid external media) with a pKa value (negative log of the acid dissociation constant) of 5.67. 6. In conclusion, Ibeta-globin may be due to the presence of xClC-5 in the oocyte plasma membrane playing a role as an anion channel whereas Inative may represent an endogenous current induced by xClC-5 cRNA injection. The use of antibodies will facilitate the tissue and subcellular localization of xClC-5 and the identification of its physiological role.