Perioperative dexmedetomidine and 5-year survival in patients undergoing cardiac surgery.

BACKGROUND: Dexmedetomidine sedation has been associated with favourable outcomes after surgery. We aimed to assess whether perioperative dexmedetomidine use is associated with improved survival after cardiac surgery. METHODS: This retrospective cohort study included 2068 patients undergoing on-pump coronary artery bypass grafting and/or valve surgery. Among them, 1029 patients received dexmedetomidine, and 1039 patients did not. Intravenous dexmedetomidine infusion of 0.007 µg kg-1 min-1 was initiated before or immediately after cardiopulmonary bypass and lasted for < 24 h. The primary outcome was 5-year survival after cardiac surgery. The propensity scores matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting approaches were used to minimise bias. Survival analyses were performed with Cox proportional-hazard models. RESULTS: The median age was 63 yr old and the male to female ratio was 71:29 in both groups. Baseline covariates were balanced between groups after adjustment using PSM, IPTW, or overlap weighting. Patients receiving dexmedetomidine in cardiac surgical procedures had higher survival during postoperative 5 yr in unadjusted analysis (hazard ratio [HR]=0.63; 95% confidence interval [CI], 0.51-0.78; P<0.001), and after adjustment with PSM (HR=0.63; 95% CI, 0.45-0.89; P=0.009), IPTW (HR=0.70; 95% CI, 0.51-0.95; P=0.023), or overlap weighting (HR=0.67; 95% CI, 0.51-0.89; P=0.006). The 5-yr mortality rate after cardiac surgery was 13% and 20% in the dexmedetomidine and non-dexmedetomidine groups, respectively (PSM adjusted odds ratio=0.61; 95% CI, 0.42-0.89; P=0.010). CONCLUSION: Perioperative dexmedetomidine infusion was associated with improved 5-yr survival in patients undergoing cardiac surgery.

Effect of Dexmedetomidine on Cardiac Surgery-Associated Acute Kidney Injury: A Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials.

OBJECTIVE: Cardiac surgery-associated acute kidney injury (CS-AKI) is associated with high mortality rates. This study aimed to determine the effects of perioperative dexmedetomidine (DEX) administration on CS-AKI in adult patients. DESIGN: A meta-analysis with trial sequential analysis of randomized controlled trials. SETTING: PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases were searched up to March 11, 2019 for relevant articles. The study protocol was registered at the International Prospective Register of Systematic Reviews (registration number: CRD42019128139). PARTICIPANTS: Adult patients undergoing cardiac surgery. INTERVENTIONS: Dexmedetomidine compared with controls. MEASUREMENTS AND MAIN RESULTS: Nine randomized controlled trials with a total of 1,308 patients were included. Use of DEX significantly reduced the incidence of CS-AKI (risk ratio = 0.60, 95% confidence interval = 0.41-0.87, p = 0.008, I2 = 30%), without significant publication bias. The trial sequential analysis result suggested that there was enough evidence for this outcome. Sensitivity analysis confirmed the robustness of the result. The improvement of CS-AKI was primarily significant in preoperative and/or intraoperative administration of DEX with or without postoperative continuation, patients with age ≥60 years, and studies with low risk of bias. The subgroup analysis did not show statistical differences. Dexmedetomidine use also was associated with less prolonged ventilation and lower incidences of pulmonary complications and delirium postoperatively. The level of evidence was high for the incidence of CS-AKI on the Grading of Recommendations Assessment, Development and Evaluation profile. CONCLUSION: Perioperative DEX administration provided protective effects against CS-AKI, especially when initiated before and during surgery in elderly patients.

Ryanodine Receptor to Mitochondrial Reactive Oxygen Species Pathway Plays an Important Role in Chronic Human Immunodeficiency Virus gp120MN-Induced Neuropathic Pain in Rats.

BACKGROUND: Chronic pain is one of the most common complaints in patients with human immunodeficiency virus (HIV)-associated sensory neuropathy. Ryanodine receptor (RyR) and mitochondrial oxidative stress are involved in neuropathic pain induced by nerve injury. Here, we investigated the role of RyR and mitochondrial superoxide in neuropathic pain induced by repeated intrathecal HIV glycoprotein 120 (gp120) injection. METHODS: Recombinant HIV glycoprotein gp120MN was intrathecally administered to induce neuropathic pain. Mechanical threshold was tested using von Frey filaments. Peripheral nerve fiber was assessed by the quantification of the intraepidermal nerve fiber density in the skin of the hindpaw. The expression of spinal RyR was examined using Western blots. Colocalization of RyR with neuronal nuclei (NeuN; neuron marker), glial fibrillary acidic protein (GFAP; astrocyte marker), or ionizing calcium-binding adaptor molecule 1 (Iba1; microglia marker) in the spinal cord was examined using immunohistochemistry. MitoSox-positive profiles (a mitochondrial-targeted fluorescent superoxide indicator) were examined. The antiallodynic effects of intrathecal administration of RyR antagonist, dantrolene (a clinical drug for malignant hyperthermia management), or selective mitochondrial superoxide scavenger, Mito-Tempol, were evaluated in the model. RESULTS: We found that repeated but not single intrathecal injection of recombinant protein gp120 induced persistent mechanical allodynia. Intraepidermal nerve fibers in repeated gp120 group was lower than that in sham at 2 weeks, and the difference in means (95% confidence interval) was 8.495 (4.79-12.20), P = .0014. Repeated gp120 increased expression of RyR, and the difference in means (95% confidence interval) was 1.50 (0.504-2.495), P = .007. Repeated gp120 also increased mitochondrial superoxide cell number in the spinal cord, and the difference in means (95% confidence interval) was 6.99 (5.99-8.00), P < .0001. Inhibition of spinal RyR or selective mitochondrial superoxide scavenger dose dependently reduced mechanical allodynia induced by repeated gp120 injection. RyR and mitochondrial superoxide were colocalized in the neuron, but not glia. Intrathecal injection of RyR inhibitor lowered mitochondrial superoxide in the spinal cord dorsal horn in the gp120 neuropathic pain model. CONCLUSIONS: These data suggest that repeated intrathecal HIV gp120 injection induced an acute to chronic pain translation in rats, and that neuronal RyR and mitochondrial superoxide in the spinal cord dorsal horn played an important role in the HIV neuropathic pain model. The current results provide evidence for a novel approach to understanding the molecular mechanisms of HIV chronic pain and treating chronic pain in patients with HIV.

Hospitals with greater diversities of physiologically complex procedures do not achieve greater surgical growth in a market with stable numbers of such procedures.

STUDY OBJECTIVE: Although having a large diversity of types of procedures has a substantial operational impact on the surgical suites of hospitals, the strategic importance is unknown. In the current study, we used longitudinal data for all hospitals and patient ages in the State of Florida to evaluate whether hospitals with greater diversity of types of physiologically complex major therapeutic procedures (PCMTP) also had greater rates of surgical growth. DESIGN: Observational cohort study. SETTING: 1479 combinations of hospitals in the State of Florida and fiscal years, 2008-2015. MEASUREMENTS: The types of International Classification of Diseases, Ninth revision, Clinical Modification (ICD-9-CM) procedures studied were PCMT, defined as: a) major therapeutic procedure; b) >7 American Society of Anesthesiologists base units; and c) performed during a hospitalization with a Diagnosis Related Group with a mean length of stay ≥4.0days. The number of procedures of each type of PCMTP commonly performed at each hospital was calculated by taking 1/Herfindahl index (i.e., sum of the squares of the proportions of all procedures of each type of PCMTP). MAIN RESULTS: Over the 8 successive years studied, there was no change in the number of PCMTP being performed (Kendall's τb=-0.014±0.017 [standard error], P=0.44; N=1479 hospital×years). Busier and larger hospitals commonly performed more types of PCMTP, respectively categorized based on performed PCMTP (τ=0.606±0.017, P<0.0001) or hospital beds (τ=0.524±0.017, P<0.0001). There was no association between greater diversity of types of PCMTP commonly performed and greater annual growth in numbers of PCMTP (τ=0.002±0.019, P=0.91; N=1295 hospital×years). Conclusions were the same with multiple sensitivity analyses. Post hoc, it was recognized that hospitals performing a greater diversity of PCMTP were more similar to the aggregate of other hospitals within the same health district (τ=0.550±0.017, P<0.0001). CONCLUSIONS: During a period with no overall growth in PCMTP, hospitals with greater diversities of types of PCMTP had growth that was, at most, minimally larger than that of the smaller hospitals, and vice-versa. Diversity is important operationally. From the perspective of delivering surgical care within a market, the unique contributions of each large teaching hospital performing many different types of PCMTP needs to be considered relative to the combined capabilities of other hospitals in its region.

Phosphorylated CCAAT/Enhancer Binding Protein ß Contributes to Rat HIV-Related Neuropathic Pain: In Vitro and In Vivo Studies.

Chronic pain is increasingly recognized as an important comorbidity of HIV-infected patients, however, the exact molecular mechanisms of HIV-related pain are still elusive. CCAAT/enhancer binding proteins (C/EBPs) are expressed in various tissues, including the CNS. C/EBPß, one of the C/EBPs, is involved in the progression of HIV/AIDS, but the exact role of C/EBPß and its upstream factors are not clear in HIV pain state. Here, we used a neuropathic pain model of perineural HIV envelope glycoprotein gp120 application onto the rat sciatic nerve to test the role of phosphorylated C/EBPß (pC/EBPß) and its upstream pathway in the spinal cord dorsal horn (SCDH). HIV gp120 induced overexpression of pC/EBPß in the ipsilateral SCDH compared with contralateral SCDH. Inhibition of C/EBPß using siRNA against C/EBPß reduced mechanical allodynia. HIV gp120 also increased TNFα, TNFRI, mitochondrial superoxide (mtO2·-), and pCREB in the ipsilateral SCDH. ChIP-qPCR assay showed that pCREB enrichment on the C/EBPß gene promoter regions in rats with gp120 was higher than that in sham rats. Intrathecal TNF soluble receptor I (functionally blocking TNFα bioactivity) or knockdown of TNFRI using antisense oligodeoxynucleotide against TNFRI reduced mechanical allodynia, and decreased mtO2·-, pCREB and pC/EBPß. Intrathecal Mito-tempol (a mitochondria-targeted O2·-scavenger) reduced mechanical allodynia and decreased pCREB and pC/EBPß. Knockdown of CREB with antisense oligodeoxynucleotide against CREB reduced mechanical allodynia and lowered pC/EBPß. These results suggested that the pathway of TNFα/TNFRI-mtO2·--pCREB triggers pC/EBPß in the HIV gp120-induced neuropathic pain state. Furthermore, we confirmed the pathway using both cultured neurons treated with recombinant TNFα in vitro and repeated intrathecal injection of recombinant TNFα in naive rats. This finding provides new insights in the understanding of the HIV neuropathic pain mechanisms and treatment.SIGNIFICANCE STATEMENT Painful HIV-associated sensory neuropathy is a neurological complication of HIV infection. Phosphorylated C/EBPß (pC/EBPß) influences AIDS progression, but it is still not clear about the exact role of pC/EBPß and the detailed upstream factors of pC/EBPß in HIV-related pain. In a neuropathic pain model of perineural HIV gp120 application onto the sciatic nerve, we found that pC/EBPß was triggered by TNFα/TNFRI-mtO2·--pCREB signaling pathway. The pathway was confirmed by using cultured neurons treated with recombinant TNFα in vitro, and by repeated intrathecal injection of recombinant TNFα in naive rats. The present results revealed the functional significance of TNFα/TNFRI-mtO2·--pCREB-pC/EBPß signaling in HIV neuropathic pain, and should help in the development of more specific treatments for neuropathic pain.

Large Variability in the Diversity of Physiologically Complex Surgical Procedures Exists Nationwide Among All Hospitals Including Among Large Teaching Hospitals.

BACKGROUND: Multiple previous studies have shown that having a large diversity of procedures has a substantial impact on quality management of hospital surgical suites. At hospitals with substantial diversity, unless sophisticated statistical methods suitable for rare events are used, anesthesiologists working in surgical suites will have inaccurate predictions of surgical blood usage, case durations, cost accounting and price transparency, times remaining in late running cases, and use of intraoperative equipment. What is unknown is whether large diversity is a feature of only a few very unique set of hospitals nationwide (eg, the largest hospitals in each state or province). METHODS: The 2013 United States Nationwide Readmissions Database was used to study heterogeneity among 1981 hospitals in their diversities of physiologically complex surgical procedures (ie, the procedure codes). The diversity of surgical procedures performed at each hospital was quantified using a summary measure, the number of different physiologically complex surgical procedures commonly performed at the hospital (ie, 1/Herfindahl). RESULTS: A total of 53.9% of all hospitals commonly performed <10 physiologically complex procedures (lower 99% confidence limit [CL], 51.3%). A total of 14.2% (lower 99% CL, 12.4%) of hospitals had >3-fold larger diversity (ie, >30 commonly performed physiologically complex procedures). Larger hospitals had greater diversity than the small- and medium-sized hospitals (P < .0001). Teaching hospitals had greater diversity than did the rural and urban nonteaching hospitals (P < .0001). A total of 80.0% of the 170 large teaching hospitals commonly performed >30 procedures (lower 99% CL, 71.9% of hospitals). However, there was considerable variability among the large teaching hospitals in their diversity (interquartile range of the numbers of commonly performed physiologically complex procedures = 19.3; lower 99% CL, 12.8 procedures). CONCLUSIONS: The diversity of procedures represents a substantive differentiator among hospitals. Thus, the usefulness of statistical methods for operating room management should be expected to be heterogeneous among hospitals. Our results also show that "large teaching hospital" alone is an insufficient description for accurate prediction of the extent to which a hospital sustains the operational and financial consequences of performing a wide diversity of surgical procedures. Future research can evaluate the extent to which hospitals with very large diversity are indispensable in their catchment area.

Gene therapy with HSV encoding p55TNFR gene for HIV neuropathic pain: an evidence-based mini-review.

While effective antiretroviral treatment makes human immunodeficiency virus (HIV)-related death decreased dramatically, neuropathic pain becomes one of the most common complications in patients with HIV/acquired immunodeficiency syndrome (AIDS). The exact mechanisms of HIV-related neuropathic pain are not well understood yet, and no effective therapy is for HIV-pain. Evidence has shown that proinflammatory factors (e.g., tumor necrosis factor alpha (TNFα)) released from glia, are critical to contributing to chronic pain. Preclinical studies have demonstrated that non-replicating herpes simplex virus (HSV)-based vector expressing human enkephalin reduces inflammatory pain, neuropathic pain, or cancer pain in animal models. In this review, we describe recent advances in the use of HSV-based gene transfer for the treatment of HIV pain, with a special focus on the use of HSV-mediated soluble TNF receptor I (neutralizing TNFα in function) in HIV neuropathic pain model.

Intraoperative Handoffs Among Anesthesia Providers Increase the Incidence of Documentation Errors for Controlled Drugs.

BACKGROUND: When electronic anesthesia records are compared to pharmacy transactions, discrepancies in total doses of controlled drugs are commonly found (≈16% of cases), potentially affecting patient safety and placing hospitals at risk for regulatory action. Errors (≈5%) persisted even with near real-time drug reconciliation feedback to providers. A study was conducted to test the hypothesis of greater risks of discrepancy for longer-duration cases and for intraoperative handoff involving a permanent handoff of care. METHODS: Anesthesia drug documentation and pharmacy transaction data were examined for all anesthetics between May 2014 and September 2015 at an academic medical center, and discrepancies between the two systems were determined. Nine logistic regression models were constructed to evaluate the influence of covariates (for example, case duration, general anesthesia vs. sedation, and handoff involving a permanent transfer of patient care) on the presence of a discrepancy. Linear regression was also performed between case duration decile and the logit (discrepancy rate), stratified by anesthesia type and handoff. RESULTS: For all models, handoffs were associated with higher discrepancy rates (p <10-6; odds ≥ 1.38). There was a progressive increase in discrepancy rates as a function of the case duration. CONCLUSIONS: Handoffs involving a permanent transfer of patient care during cases increase the risk of controlled drug discrepancies. Staff scheduling and assignment decisions to decrease the chance of a handoff occurring should help mitigate this. In addition, future studies should examine ways to improve the handoff process related to controlled drugs (for example, a formal, structured processes in the anesthesia information management system).

Readmissions to Different Hospitals After Common Surgical Procedures and Consequences for Implementation of Perioperative Surgical Home Programs.

BACKGROUND: We consider whether there should be greater priority of information sharing about postacute surgical resources used: (1) at skilled nursing facilities or inpatient rehabilitation hospitals to which patients are transferred upon discharge (when applicable) versus (2) at different hospitals where readmissions occur. Obtaining and storing data electronically from these 2 sources for Perioperative Surgical Home initiatives are dissimilar; both can be challenging depending on the country and health system. METHODS: Using the 2013 US Nationwide Readmissions Database, we studied discharges of surgical diagnosis-related group (DRG) with US national median length of stay (LOS) ≥ 3 days and ≥ 10 hospitals each with ≥ 100 discharges for the Medicare Severity DRG. RESULTS: Nationwide, 16.15% (95% confidence interval [CI], 15.14%-17.22%) of discharges were with a disposition of "not to home" (ie, transfer to a skilled nursing facility or an inpatient rehabilitation hospital). Within 30 days, 0.88% of discharges (0.82%-0.95%) were followed by readmission and to a different hospital than the original hospital where the surgery was performed. Among all discharges, disposition "not to home" versus "to home" was associated with greater odds that the patient would have readmission within 30 days and to a different hospital than where the surgery was performed (2.11, 95% CI, 1.96-2.27; P < .0001). In part, this was because disposition "not to home" was associated with greater odds of readmission to any hospital (1.90, 95% CI, 1.82-1.98; P < .0001). In addition, among the subset of discharges with readmission within 30 days, disposition "not to home" versus "to home" was associated with greater odds that the readmission was to a different hospital than where the surgery was performed (1.20, 95% CI, 1.11-1.31; P < .0001). There was no association between the hospitals' median LOS for the DRG and the odds that readmission was to a different hospital (P = .82). The odds ratio per each 1 day decrease in the hospital median LOS was 1.01 (95% CI, 0.91-1.12). CONCLUSIONS: Departments and hospitals wishing to demonstrate the value of their Perioperative Surgical Home initiatives, or to calculate risk assumption contracts, should ensure that their informatics priorities include obtaining accurate data on resource use at postacute care facilities such as skilled nursing facilities. Although approximately a quarter of readmissions are to different hospitals than where surgery was performed, provided that is recognized, obtaining those missing data is of less importance.

Inhibition of Mitochondrial Fission Protein Reduced Mechanical Allodynia and Suppressed Spinal Mitochondrial Superoxide Induced by Perineural Human Immunodeficiency Virus gp120 in Rats.

BACKGROUND: Mitochondria play an important role in many cellular and physiologic functions. Mitochondria are dynamic organelles, and their fusion and fission regulate cellular signaling, development, and mitochondrial homeostasis. The most common complaint of human immunodeficiency virus (HIV)-sensory neuropathy is pain on the soles in patients with HIV, but the exact molecular mechanisms of HIV neuropathic pain are not clear. In the present study, we investigated the role of mitochondrial dynamin-related protein 1 (Drp1, a GTPase that mediates mitochondrial fission) in the perineural HIV coat glycoprotein gp120-induced neuropathic pain state. METHODS: Neuropathic pain was induced by the application of recombinant HIV-1 envelope protein gp120 into the sciatic nerve. Mechanical threshold was tested using von Frey filaments. The mechanical threshold response was assessed over time using the area under curves. Intrathecal administration of antisense oligodeoxynucleotide (ODN) against Drp1, mitochondrial division inhibitor-1 (mdivi-1), or phenyl-N-tert-butylnitrone (a reactive oxygen species scavenger) was given. The expression of spinal Drp1 was examined using western blots. The expression of mitochondrial superoxide in the spinal dorsal horn was examined using MitoSox imaging. RESULTS: Intrathecal administration of either antisense ODN against Drp1 or mdivi-1 decreased mechanical allodynia (a sensation of pain evoked by nonpainful stimuli) in the gp120 model. Intrathecal ODN or mdivi-1 did not change basic mechanical threshold in sham surgery rats. Intrathecal Drp1 antisense ODN decreased the spinal expression of increased Drp1 protein induced by peripheral gp120 application. Intrathecal phenyl-N-tert-butylnitrone reduced mechanical allodynia. Furthermore, both intrathecal Drp1 antisense ODN and mdivi-1 reversed the upregulation of mitochondrial superoxide in the spinal dorsal horn in the gp120 neuropathic pain state. CONCLUSIONS: These data suggest that mitochondrial division plays a substantial role in the HIV gp120-related neuropathic pain state through mitochondrial reactive oxygen species and provides evidence for a novel approach to treating chronic pain in patients with HIV.

The impact of anesthesia providers on major morbidity following screening colonoscopies.

BACKGROUND AND AIMS: Few studies evaluate the impact of anesthesia providers during procedures, such as colonoscopy, on low-risk patients. The objective of this study was to compare the effect of anesthesia providers on several outcome variables, including major morbidity, following screening colonoscopies. METHODS: A propensity-matched cohort study of 14,006 patients who enrolled with a national insurer offering health maintenance organization (HMO), preferred provider organization (PPO), and Medicare Advantage plans for a screening colonoscopy between July 1, 2005 and June 30, 2007 were studied. Records were evaluated for completion of the colonoscopy, new cancer diagnosis (colon, anal, rectal) within 6 months of the colonoscopy, new primary diagnosis of myocardial infarction (MI), new primary diagnosis of stroke, hospital admission within 7 days of the colonoscopy, and adherence to guidelines for use of anesthesia providers. RESULTS: The presence of an anesthesia provider did not affect major morbidity or the percent of completed exams. Overall morbidity within 7 days was very low. When an anesthesia provider was present, a nonsignificant trend toward greater cancer detection within 6 months of the procedure was observed. Adherence to national guidelines regarding the use of anesthesia providers for low-risk patients was poor. CONCLUSION: A difference in outcome associated with the presence or absence of an anesthesia provider during screening colonoscopy in terms of MI, stroke, or hospital admission within 7 days of the procedure was not observed. Adherence to published guidelines for the use of anesthesia providers is low. The incidence of completed exams was unaffected by the presence of an anesthesia provider. However, a nonstatistically significant trend toward increased cancer detection requires further study.

A matrix model for valuing anesthesia service with the resource-based relative value system.

BACKGROUND: The purpose of this study was to propose a new crosswalk using the resource-based relative value system (RBRVS) that preserves the time unit component of the anesthesia service and disaggregates anesthesia billing into component parts (preoperative evaluation, intraoperative management, and postoperative evaluation). The study was designed as an observational chart and billing data review of current and proposed payments, in the setting of a preoperative holing area, intraoperative suite, and post anesthesia care unit. In total, 1,195 charts of American Society of Anesthesiology (ASA) physical status 1 through 5 patients were reviewed. No direct patient interventions were undertaken. RESULTS: Spearman correlations between the proposed RBRVS billing matrix payments and the current ASA relative value guide methodology payments were strong (r=0.94-0.96, P<0.001 for training, test, and overall). The proposed RBRVS-based billing matrix yielded payments that were 3.0%±1.34% less than would have been expected from commercial insurers, using standard rates for commercial ASA relative value units and RBRVS relative value units. Compared with current Medicare reimbursement under the ASA relative value guide, reimbursement would almost double when converting to an RBRVS billing model. The greatest increases in Medicare reimbursement between the current system and proposed billing model occurred as anesthetic management complexity increased. CONCLUSION: The new crosswalk correlates with existing evaluation and management and intensive care medicine codes in an essentially revenue neutral manner when applied to the market-based rates of commercial insurers. The new system more highly values delivery of care to more complex patients undergoing more complex surgery and better represents the true value of anesthetic case management.

IL-10 mediated by herpes simplex virus vector reduces neuropathic pain induced by HIV gp120 combined with ddC in rats.

BACKGROUND: HIV-associated sensory neuropathy affects over 50% of HIV patients and is a common peripheral nerve complication of HIV infection and highly active antiretroviral therapy (HAART). Evidence shows that painful HIV sensory neuropathy is influenced by neuroinflammatory events that include the proinflammatory molecules, MAP Kinase, tumor necrosis factor-α (TNFα), stromal cell-derived factor 1-α (SDF1α), and C-X-C chemokine receptor type 4 (CXCR4). However, the exact mechanisms of painful HIV sensory neuropathy are not known, which hinders our ability to develop effective treatments. In this study, we investigated whether inhibition of proinflammatory factors reduces the HIV-associated neuropathic pain state. RESULTS: Neuropathic pain was induced by peripheral HIV coat protein gp120 combined with 2',3'-dideoxycytidine (ddC, one of the nucleoside reverse transcriptase inhibitors (NRTIs)). Mechanical threshold was tested using von Frey filament fibers. Non-replicating herpes simplex virus (HSV) vectors expressing interleukin 10 (IL10) were inoculated into the hindpaws of rats. The expression of TNFα, SDF1α, and CXCR4 in the lumbar spinal cord and L4/5 dorsal root ganglia (DRG) was examined using western blots. IL-10 expression mediated by the HSV vectors resulted in a significant elevation of mechanical threshold. The anti-allodynic effect of IL-10 expression mediated by the HSV vectors lasted more than 3 weeks. The area under the effect-time curves (AUC) in mechanical threshold in rats inoculated with the HSV vectors expressing IL-10, was increased compared with the control vectors, indicating antinociceptive effect of the IL-10 vectors. The HSV vectors expressing IL-10 also concomitantly reversed the upregulation of p-p38, TNFα, SDF1α, and CXCR4 induced by gp120 in the lumbar spinal dorsal horn and/or the DRG at 2 and/or 4 weeks. CONCLUSION: The blocking of the signaling of these proinflammatory molecules is able to reduce HIV-related neuropathic pain, which provide a novel mechanism-based approach to treating HIV-associated neuropathic pain using gene therapy.

Interleukin 10 mediated by herpes simplex virus vectors suppresses neuropathic pain induced by human immunodeficiency virus gp120 in rats.

BACKGROUND: Human immunodeficiency virus (HIV)-associated sensory neuropathy is a common neurological complication of HIV infection affecting up to 30% of HIV-positive individuals. However, the exact neuropathological mechanisms remain unknown, which hinders our ability to develop effective treatments for HIV-related neuropathic pain (NP). In this study, we tested the hypothesis that inhibition of proinflammatory factors with overexpression of interleukin (IL)-10 reduces HIV-related NP in a rat model. METHODS: NP was induced by the application of recombinant HIV-1 envelope protein gp120 into the sciatic nerve. The hindpaws of rats were inoculated with nonreplicating herpes simplex virus (HSV) vectors expressing anti-inflammatory cytokine IL-10 or control vector. Mechanical threshold was tested using von Frey filaments before and after treatments with the vectors. The mechanical threshold response was assessed over time using the area under curves. The expression of phosphorylated p38 mitogen-activated kinase, tumor necrosis factor-α, stromal cell-derived factor-1α, and C-X-C chemokine receptor type 4 in both the lumbar spinal cord and the L4/5 dorsal root ganglia (DRG), was examined at 14 and 28 days after vector inoculation using Western blots. RESULTS: We found that in the gp120-induced NP model, IL-10 overexpression mediated by the HSV vector resulted in a significant elevation of the mechanical threshold that was apparent on day 3 after vector inoculation compared with the control vector (P < 0.001). The antiallodynic effect of the single HSV vector inoculation expressing IL-10 lasted >28 days. The area under curve in the HSV vector expressing IL-10 was increased compared with that in the control vector (P < 0.0001). HSV vectors expressing IL-10 reversed the upregulation of phosphorylated p38 mitogen-activated kinase, tumor necrosis factor-α, stromal cell-derived factor-1α, and C-X-C chemokine receptor type 4 expression at 14 and/or 28 days in the DRG and/or the spinal dorsal horn. CONCLUSIONS: Our studies demonstrate that blocking the signaling of these proinflammatory molecules in the DRG and/or the spinal cord using the HSV vector expressing IL-10 is able to reduce HIV-related NP. These results provide new insights on the potential mechanisms of HIV-associated NP and a proof of concept for treating painful HIV sensory neuropathy with this type of gene therapy.

Frequency of interactions and hand disinfections among anesthesiologists while providing anesthesia care in the operating room: induction versus maintenance.

We evaluated the behaviors of anesthesiologists during induction and maintenance of anesthesia. Contacts with surfaces occurred a mean (±standard error) of 154.8 ± 7.7 and 60 ± 3.1 times per hour during induction and maintenance, respectively (P < .0001). Hand hygiene events were 1.8 ± 0.27 per hour during induction versus 1.19 ± 0.27 during maintenance (P = .018).

Mechanical allodynia induced by nucleoside reverse transcriptase inhibitor is suppressed by p55TNFSR mediated by herpes simplex virus vector through the SDF1α/CXCR4 system in rats.

BACKGROUND: In the human immunodeficiency virus (HIV)-associated sensory neuropathy, neuropathic pain associated with the use of nucleoside reverse transcriptase inhibitors (NRTIs) in patients with HIV/acquired immunodeficiency syndrome is clinically common. While evidence demonstrates that neuropathic pain is influenced by neuroinflammatory events that include the proinflammatory molecules, tumor necrosis factor-α (TNF-α), stromal cell-derived factor 1-α (SDF1-α), and C-X-C chemokine receptor type 4 (CXCR4), the detailed mechanisms by which NRTIs contribute to the development of neuropathic pain are not known. In this study, we investigated the role of these proinflammatory molecules in the dorsal root ganglion (DRG) and the spinal dorsal horn in NRTIs-mediated neuropathic pain state. METHODS: Neuropathic pain was induced by intraperitoneal administration of 2',3'-dideoxycytidine (ddC, one of the NRTIs). Mechanical threshold was tested using von Frey filament fibers. Nonreplicating herpes simplex virus (HSV) vectors expressing p55 TNF soluble receptor (p55TNFSR) were inoculated into hindpaw of rats. The expression of TNF-α, SDF1-α, and CXCR4 in both the lumbar spinal cord and the L4/5 DRG was examined using Western blots. Intrathecal CXCR4 antagonist was administered. RESULTS: The present study demonstrated that (1) systemic ddC induced upregulation of TNF-α, SDF1-α, and CXCR4 in both the lumbar spinal cord and the L4/5 DRG; (2) p55TNFSR mediated by a nonreplicating HSV vector reversed mechanical allodynia induced by systemic ddC; (3) intrathecal administration of the CXCR4 antagonist AMD3100 increased mechanical threshold; and (4) HSV vector expressing p55TNFSR reversed upregulation of TNF-α, SDF1-α, and CXCR4 induced by ddC in the lumbar spinal dorsal horn and the DRG. CONCLUSIONS: Our studies demonstrate that TNF-α through the SDF1/CXCR4 system is involved in the NRTIs-related neuropathic pain state and that blocking the signaling of these proinflammatory molecules is able to reduce NRTIs-related neuropathic pain. These results provide a novel mechanism-based approach (gene therapy) to treating HIV-associated neuropathic pain.

Decreasing operating room environmental pathogen contamination through improved cleaning practice.

OBJECTIVE: Potential transmission of organisms from the environment to patients is a concern, especially in enclosed settings, such as operating rooms, in which there are multiple and frequent contacts between patients, provider's hands, and environmental surfaces. Therefore, adequate disinfection of operating rooms is essential. We aimed to determine the change in both the thoroughness of environmental cleaning and the proportion of environmental surfaces within operating rooms from which pathogenic organisms were recovered. DESIGN: Prospective environmental study using feedback with UV markers and environmental cultures. SETTING: A 1,500-bed county teaching hospital. PARTICIPANTS: Environmental service personnel, hospital administration, and medical and nursing leadership. RESULTS: The proportion of UV markers removed (cleaned) increased from 0.47 (284 of 600 markers; 95% confidence interval [CI], 0.42-0.53) at baseline to 0.82 (634 of 777 markers; 95% CI, 0.77-0.85) during the last month of observations ([Formula: see text]). Nevertheless, the percentage of samples from which pathogenic organisms (gram-negative bacilli, Staphylococcus aureus, and Enterococcus species) were recovered did not change throughout our study. Pathogens were identified on 16.6% of surfaces at baseline and 12.5% of surfaces during the follow-up period ([Formula: see text]). However, the percentage of surfaces from which gram-negative bacilli were recovered decreased from 10.7% at baseline to 2.3% during the follow-up period ([Formula: see text]). CONCLUSIONS: Feedback using Gram staining of environmental cultures and UV markers was successful at improving the degree of cleaning in our operating rooms.

An economic evaluation of a systems-based strategy to expedite surgical treatment of hip fractures.

BACKGROUND: A recent systematic review has indicated that mortality within the first year after hip fracture repair increases significantly if the time from hospital admission to surgery exceeds forty-eight hours. Further investigation has shown that avoidable, systems-based factors contribute substantially to delay in surgery. In this study, an economic evaluation was conducted to determine the cost-effectiveness of a hypothetical scenario in which resources are allocated to expedite surgery so that it is performed within forty-eight hours after admission. METHODS: We created a decision tree to tabulate incremental cost and quality-adjusted life years in order to evaluate the cost-effectiveness of two potential strategies. Several factors, including personnel cost, patient volume, percentage of patients receiving surgical treatment within forty-eight hours, and mortality associated with delayed surgery, were considered. One strategy focused solely on expediting preoperative evaluation by employing personnel to conduct the necessary diagnostic tests and a hospitalist physician to conduct the medical evaluation outside of regular hours. The second strategy added an on-call team (nurse, surgical technologist, and anesthesiologist) to staff an operating room outside of regular hours. RESULTS: The evaluation-focused strategy was cost-effective, with an incremental cost-effectiveness ratio of $2318 per quality-adjusted life year, and became cost-saving (a dominant therapeutic approach) if =93% of patients underwent expedited surgery, the hourly cost of retaining a diagnostic technologist on call was <$20.80, or <15% of the hospitalist's salary was funded by the strategy. The second strategy, which added an on-call surgical team, was also cost-effective, with an incremental cost-effectiveness ratio of $43,153 per quality-adjusted life year. Sensitivity analysis revealed that this strategy remained cost-effective if the odds ratio of one-year mortality associated with delayed surgery was >1.28, =88% of patients underwent early surgery, or =339.9 patients with a hip fracture were treated annually. CONCLUSIONS: The results of our study suggest that systems-based solutions to minimize operative delay, such as a dedicated on-call support team, can be cost-effective. Additionally, an evaluation-focused intervention can be cost-saving, depending on its success rate and associated personnel cost.