Timeliness of data entry in Wisconsin Immunization Registry by Wisconsin pharmacies.

OBJECTIVE: To assess the association of various immunization- and pharmacy-related factors with the timeliness of pharmacy data entry in a state immunization information system. DESIGN: A cross-sectional study was conducted. SETTING AND PARTICIPANTS: Data for 2,040,248 immunizations administered by pharmacies in Wisconsin during 2012-2017 were collected from the Wisconsin Immunization Registry (WIR). Variables, including the submission method, immunization administration year, vaccine type, and recipient age, were analyzed through multivariate logistic regression to determine if they had a relationship with data entry timeliness. Pharmacists were surveyed on immunization data entry practices to corroborate analysis findings. OUTCOME MEASURES: Timeliness of immunization data entry in WIR was measured as a binary variable: 7 days or fewer or more than 7 days after immunization. RESULTS: Influenza immunizations were statistically significantly less likely to be timely compared with noninfluenza immunizations (odds ratio [OR] 0.719 [95% CI 0.712-0.726]; P < 0.0001). Immunizations administered to individuals aged more than 18 years were less timely compared with immunizations administered to individuals aged 6-18 years. The magnitude showed a slight difference in timeliness but without statistical significance (0.989 [95% CI 0.972-1.006]; P > 0.05). For submission method, flat-file submission was less likely to be timely compared with manual entry (0.48 [95% CI 0.475-0.486]; P < 0.0001). Health Level-7 submission, involving the electronic exchange of information with electronic health systems, was much more likely to be timely compared with manual entry (1.989 [95% CI 1.972-2.007]; P < 0.0001). With each successive year, from 2012 to 2017, immunizations were entered in a less timely manner (0.981 [95% CI 0.979-0.983]; P < 0.0001). CONCLUSIONS: Timeliness of pharmacy data entry in WIR was associated with entry method, vaccine type, and immunization administration year. We hope to identify ways to help pharmacies improve immunization data entry in WIR and facilitate the communication of immunization information among providers.

Factors influencing treatment team recommendations to review tribunals for forensic psychiatric patients.

It is the responsibility of forensic psychiatric hospitals to detain and treat patients, gradually reintegrating them into society; decisions to release patients must balance risk to the public with maintaining the least restrictive environment for patients. Little is known about the factors considered when making such decisions and whether these factors have been empirically linked to future risk of violence. The current study explores the factors predictive of forensic treatment teams' recommendations for patients under the care of the Ontario Review Board (ORB). Factors differ depending on level of security; decisions on medium secure units were influenced by the presence of active symptoms and patients' overall violence risk level and decisions made on minimum secure units were influenced by the number of critical incidents that occurred within the recommendation year. Understanding the factors used to make recommendations to the ORB tribunal helps treatment teams to reflect on their own decision-making practices. Furthermore, the results serve to inform us about factors that influence length of stay for forensic psychiatric patients. Copyright © 2016 John Wiley & Sons, Ltd.

Tracheostomy in mechanical ventilation.

Airway access for mechanical ventilation (MV) can be provided either by orotracheal intubation (OTI) or tracheostomy tube. During episodes of acute respiratory failure, patients are commonly ventilated through an orotracheal tube that represents an easy and rapid initial placement of the airway device. OTI avoids acute surgical complications such as bleeding, nerve and posterior tracheal wall injury, and late complications such as wound infection and tracheal lumen stenosis that may emerge due to tracheostomy tube placement. Tracheostomy is often considered when MV is expected to be applied for prolonged periods or for the improvement of respiratory status, as this approach provides airway protection, facilitates access for secretion removal, improves patient comfort, and promotes progression of care in and outside the intensive care unit (ICU). The aim of this review is to assess the frequency and performance of different surgical or percutaneous dilational tracheostomy and timing and safety procedures associated with the use of fiberoptic bronchoscopy and ultrasounds. Moreover, we analyzed the performance based on National European surveys to assess the current tracheostomy practice in ICUs.

Articaine: dental practitioner use, basis of perception and evidence-based dentistry-a cross-sectional study.

BACKGROUND: Limited data exist on dental practitioner use and perceptions of articaine. This study is a cross-sectional survey of dental practitioners from January, 2021 to ascertain the extent of their use of the dental local anaesthetic, articaine, the basis of their perceptions about articaine and whether current practices are in line with recent evidence regarding articaine safety and efficacy. METHOD: An anonymous survey was designed using the SAP Qualtrics Core XM software platform and a survey link was disseminated from December 2020 to January 2021 via social media. The survey was designed as a five minute, anonymous, online questionnaire including a plain language information sheet, request for participant consent and 14 questions. Data were entered onto a Microsoft™ Excel spreadsheet and analysed qualitatively, isolating the answers into recurrent themes. RESULTS: Sixty percent of the surveyed dental practitioner used articaine as their preferred dental anaesthetic. Twenty-three percent of the dental practitioner surveyed used articaine for all of their dental procedures including inferior alveolar nerve blocks, while 40% of respondents used articaine for all their dental procedures except inferior alveolar nerve blocks. The predominant basis of dental practitioner uses and perception of articaine were their countries dental guidelines. CONCLUSION: Despite the latest findings that articaine is as safe and more efficacious as lidocaine for all routine dental treatment, 40% of survey respondents avoided articaine use for inferior alveolar blocks. Our study recognises a discrepancy between reported clinical practice and current research evidence. Further research and clarifications are needed to achieve ubiquitous practice of evidence-based dentistry.

Phosphoinositide-3 kinase gamma activity contributes to sepsis and organ damage by altering neutrophil recruitment.

RATIONALE: Sepsis is a leading cause of death in the intensive care unit, characterized by a systemic inflammatory response (SIRS) and bacterial infection, which can often induce multiorgan damage and failure. Leukocyte recruitment, required to limit bacterial spread, depends on phosphoinositide-3 kinase γ (PI3Kγ) signaling in vitro; however, the role of this enzyme in polymicrobial sepsis has remained unclear. OBJECTIVES: This study aimed to determine the specific role of the kinase activity of PI3Kγ in the pathogenesis of sepsis and multiorgan damage. METHODS: PI3Kγ wild-type, knockout, and kinase-dead mice were exposed to cecal ligation and perforation-induced sepsis and assessed for survival; pulmonary, hepatic, and cardiovascular damage; coagulation derangements; systemic inflammation; bacterial spread; and neutrophil recruitment. Additionally, wild-type mice were treated either before or after the onset of sepsis with a PI3Kγ inhibitor and assessed for survival, neutrophil recruitment, and bacterial spread. MEASUREMENTS AND MAIN RESULTS: Both genetic and pharmaceutical PI3Kγ kinase inhibition significantly improved survival, reduced multiorgan damage, and limited bacterial decompartmentalization, while modestly affecting SIRS. Protection resulted from both neutrophil-independent mechanisms, involving improved cardiovascular function, and neutrophil-dependent mechanisms, through reduced susceptibility to neutrophil migration failure during severe sepsis by maintaining neutrophil surface expression of the chemokine receptor, CXCR2. Furthermore, PI3Kγ pharmacological inhibition significantly decreased mortality and improved neutrophil migration and bacterial control, even when administered during established septic shock. CONCLUSIONS: This study establishes PI3Kγ as a key molecule in the pathogenesis of septic infection and the transition from SIRS to organ damage and identifies it as a novel possible therapeutic target.

Articaine in dentistry: an overview of the evidence and meta-analysis of the latest randomised controlled trials on articaine safety and efficacy compared to lidocaine for routine dental treatment.

OBJECTIVES: To comprehensively review the existing studies of articaine in dentistry and conduct a systematic review and meta-analysis to answer the following Population, Intervention, Comparison and Outcome question: "Is articaine a safe and efficacious local anaesthetic for routine dental treatment compared to lidocaine?" METHODS: Database searches were conducted in Medline Ovid, Medline Pubmed, Scopus, Emcare, Proquest and the Cochrane Central register of Controlled Trials. Inclusion criteria were all existing English, human, randomised controlled trials of interventions involving 4% articaine and 2% lidocaine in routine dental treatment. Twelve studies were included for meta-analysis using Cochrane Review Manager 5 software. Anaesthetic success odds ratios were calculated using a random-effects model. RESULTS: Articaine had a higher likelihood of achieving anaesthetic success than lidocaine overall and in all subgroup analyses with varying degrees of significance. Overall (OR: 2.17, 95% CI: 1.50, 3.15, I2 = 62%) articaine had 2.17 times the likelihood of anaesthetic success of lidocaine (P < 0.0001). For mandibular blocks (OR: 1.50, 95% CI: 1.14, 1.98, I2 = 0%) articaine had 1.5 times the likelihood of anaesthetic success of lidocaine (P = 0.004). For all infiltrations, maxillary and mandibular (OR: 2.78, 95% CI: 1.61, 4.79, I2 = 66%) articaine had 2.78 times the likelihood of anaesthetic success of lidocaine (P = 0.0002). None of the studies reported any major local anaesthetic-related adverse effects as a result of the interventions. CONCLUSIONS: Articaine is a safe and efficacious local anaesthetic for all routine dental procedures in patients of all ages, and more likely to achieve successful anaesthesia than lidocaine in routine dental treatment. Neither anaesthetic has a higher association with anaesthetic-related adverse effects.

Improving intravenous-to-oral antibiotic switch in children: a team-based audit and implementation approach.

Children in hospital are frequently prescribed intravenous antibiotics for longer than needed. Programmes to optimise timely intravenous-to-oral antibiotic switch may limit excessive in-hospital antibiotic use, minimise complications of intravenous therapy and allow children to go home faster. Here, we describe a quality improvement approach to implement a guideline, with team-based education, audit and feedback, for timely, safe switch from intravenous-to-oral antibiotics in hospitalised children. Eligibility for switch was based on evidence-based guidelines and supported by education and feedback. The project was conducted over 12 months in a tertiary paediatric hospital. Primary outcomes assessed were the proportion of eligible children admitted under paediatric and surgical teams switched within 24 hours, and switch timing prior to and after guideline launch. Secondary outcomes were hospital length of stay, recommencement of intravenous therapy or readmission. The percentage of children switched within 24 hours of eligibility significantly increased from 32/50 (64%) at baseline to 203/249 (82%) post-implementation (p=0.006). The median time to switch fell from 15 hours 42 min to 4 hours 20 min (p=0.0006). In addition, there was a 14-hour median reduction in hospital length of stay (p=0.008). Readmission to hospital and recommencement of intravenous therapy did not significantly change postimplementation. This education, audit and feedback approach improved timely intravenous-to-oral switch in children and also allowed for more timely discharge from hospital. The study demonstrates proof of concept for this implementation with a methodology that can be readily adapted to other paediatric inpatient settings.

Serum calcium levels are elevated among women with untreated postmenopausal breast cancer.

OBJECTIVE: Reports of an association between primary hyperparathyroidism in women and risk of breast cancer suggest an etiologic role for high serum calcium. However, data on the association between serum calcium levels and breast cancer in women without clinical hyperparathyroidism are limited. METHODS: We conducted a hospital-based case-control study among postmenopausal women in Fargo, ND. Cases were women aged 65 and older with newly diagnosed, histologically confirmed breast cancer. Controls were aged 65 and older without clinical cancer who were seen at the same hospital. RESULTS: We obtained data on 190 white cases and 172 white controls. Primary hyperparathyroidism (an abnormally high calcium level confirmed by an abnormally high serum PTH) was found in 3/190 cases and in 0/172 controls (p = 0.25). After excluding the women with primary hyperparathyroidism, the mean calcium levels among cases was 9.6 mg/dL (range, 7.5-11.0, SD = 0.47) vs. 9.4 mg/dL (7.7-10.5, 0.43) among the controls (p < 0.0001). Comparing women in the top with women in the bottom tertile of serum calcium, the multivariable-adjusted odds ratio (OR) for breast cancer was 5.21 (95% CI: 2.59-10.48). There was no relationship between serum calcium and tumor size or stage. CONCLUSION: The distribution of serum calcium levels among postmenopausal women with incident breast cancer was shifted significantly toward the right. These findings are consistent with an effect of early breast tumors on calcium homeostasis. However, the lack of association between serum calcium levels and tumor size or stage supports the hypothesis that subclinical hyperparathyroidism may increase the risk for breast cancer.

Effect of a lung protective strategy for organ donors on eligibility and availability of lungs for transplantation: a randomized controlled trial.

CONTEXT: Many potential donor lungs deteriorate between the time of brain death and evaluation for transplantation suitability, possibly because of the ventilatory strategy used after brain death. OBJECTIVE: To test whether a lung protective strategy increases the number of lungs available for transplantation. DESIGN, SETTING, AND PATIENTS: Multicenter randomized controlled trial of patients with beating hearts who were potential organ donors conducted at 12 European intensive care units from September 2004 to May 2009 in the Protective Ventilatory Strategy in Potential Lung Donors Study. Interventions Potential donors were randomized to the conventional ventilatory strategy (with tidal volumes of 10-12 mL/kg of predicted body weight, positive end-expiratory pressure [PEEP] of 3-5 cm H(2)O, apnea tests performed by disconnecting the ventilator, and open circuit for airway suction) or the protective ventilatory strategy (with tidal volumes of 6-8 mL/kg of predicted body weight, PEEP of 8-10 cm H(2)O, apnea tests performed by using continuous positive airway pressure, and closed circuit for airway suction). MAIN OUTCOME MEASURES: The number of organ donors meeting eligibility criteria for harvesting, number of lungs harvested, and 6-month survival of lung transplant recipients. RESULTS: The trial was stopped after enrolling 118 patients (59 in the conventional ventilatory strategy and 59 in the protective ventilatory strategy) because of termination of funding. The number of patients who met lung donor eligibility criteria after the 6-hour observation period was 32 (54%) in the conventional strategy vs 56 (95%) in the protective strategy (difference of 41% [95% confidence interval {CI}, 26.5% to 54.8%]; P <.001). The number of patients in whom lungs were harvested was 16 (27%) in the conventional strategy vs 32 (54%) in the protective strategy (difference of 27% [95% CI, 10.0% to 44.5%]; P = .004). Six-month survival rates did not differ between recipients who received lungs from donors ventilated with the conventional strategy compared with the protective strategy (11/16 [69%] vs 24/32 [75%], respectively; difference of 6% [95% CI, -22% to 32%]). CONCLUSION: Use of a lung protective strategy in potential organ donors with brain death increased the number of eligible and harvested lungs compared with a conventional strategy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00260676.

Advancing Community Pharmacy Practice - A Technician Product Verification Pilot to Optimize Care.

Elevating the technical role of pharmacy technicians to perform Technician Product Verification (TPV) is one strategy that has shown promise to optimize pharmacy practice models. This is done by better positioning pharmacists to provide clinical care, in line with their education and expertise. TPV permits a Validated Pharmacy Technician, as defined by the Wisconsin Pharmacy Examining Board, to verify the accuracy of a product filled by another technician. The pharmacist maintains responsibility for assessing the clinical appropriateness of the prescription, including drug utilization review, data entry, and patient counseling. During the study period, 12,891 pharmacist-verified prescriptions (baseline) and 27,447 Validated Pharmacy Technician-verified prescriptions were audited for accuracy. The aggregate verification error rate for pharmacist-verified prescriptions was 0.16% and 0.01% for Validated Pharmacy Technician-verified prescriptions. The mean error rate was significantly less for Validated Pharmacy Technician-verified prescriptions than for pharmacist-verified prescriptions (0.19 ± 0.174 % vs 0.03 ± 0.089 %, p=0.020) (Figure 3). This suggests TPV in the community pharmacy setting maintained patient safety. In this study, Validated Pharmacy Technicians were shown to be more accurate than pharmacists at performing product verification. The ability to delegate the product verification task holds the potential to free up pharmacist time for increased direct patient care. Increasing direct patient care by pharmacists in community pharmacies may have significant implications for improving patient outcomes and pharmacy quality.

Comparison of Attitudes of Wisconsin Health Care Providers and Pharmacists Toward Vaccine Administration and Perceived Barriers.

OBJECTIVE: To measure the attitudes of pharmacists and other health care providers towards vaccine administration, overall acceptance of pharmacists as immunization providers, and perceived immunization barriers in Wisconsin. METHODS: The authors conducted a cross-sectional study utilizing an online survey to assess the attitudes of pharmacists and other health care providers toward their role as immunization providers and perceived barriers to providing immunizations. The survey was distributed between November 2018 and February 2019. RESULTS: Two hundred thirty-six pharmacists and 51 other health care providers completed the survey. Of the pharmacists who responded, 203 (86%) provided immunizations. Most respondents (97.9% of pharmacists and 90.2% of other health care providers) see vaccinations as a shared professional responsibility. Both pharmacists (82.6%) and other health care providers (79.6%) believe pharmacists have adequate training to administer vaccines to patients. Immunizing pharmacists identified 2 primary barriers to providing immunizations: patients refusing vaccines for financial reasons (55%) and patients not having insurance coverage for vaccines received in a pharmacy (55%). In contrast, the primary barrier identified by non-immunizing pharmacists is other responsibilities taking precedence over vaccinating (75%). Other health care providers identified determining whether their patients' insurance will reimburse for a vaccine (52%) as their primary barrier toward providing immunizations. CONCLUSION: These surveys provide a baseline measure of the attitudes of Wisconsin pharmacists and other health care providers toward immunization provision and offer opportunities for comparison. Our findings highlight barriers, such as insurance coverage for immunizations, that may prevent pharmacists from increasing vaccination rates in Wisconsin.

Immunizations at Wisconsin Pharmacies: Results of a statewide vaccine registry analysis and pharmacist survey.

BACKGROUND: There is currently limited data in the United States on the proportion of immunization doses given at pharmacies outside the influenza vaccine. This study aims to obtain baseline information on the percentage of vaccine doses administered at pharmacies in Wisconsin and to understand the immunization barriers for Wisconsin pharmacists, to inform interventions to increase immunization access at pharmacies. METHODS: Aggregated data from the Wisconsin Immunization Registry (WIR) was obtained for all vaccines administered at pharmacies to patients over the age of six from July 2017 through June 2018. In addition, a survey on attitudes towards and barriers to vaccination was sent to 2000 Wisconsin pharmacists with 236 respondents yielding a 12% response rate. RESULTS: WIR data demonstrates that zoster and influenza vaccines have the highest proportion of doses administered at pharmacies (39% and 20%, respectively). Human papillomavirus (HPV) vaccines have the lowest proportion of doses at 0.2%. Pharmacy survey shows that 86% provide immunizations. Most stock influenza vaccines (84%), whereas much fewer stock HPV vaccines (21%). The greatest immunization barriers for the pharmacy respondents include billing and reimbursement challenges and competing demands for staff. CONCLUSIONS: Despite the barriers, community pharmacies have significant potential to address vaccination gaps. Physicians, patients, and legislative bodies are generally well-accepting of pharmacists as immunizers. Pharmacists, in order to be fully utilized as immunizers, must engage in active communication with patients and be willing to collaborate with physicians. Legislative policy and health insurance reimbursement reforms are also necessary to facilitate further pharmacist participation in immunization.

Pulmonary atelectasis during low stretch ventilation: "open lung" versus "lung rest" strategy.

OBJECTIVE: Limiting tidal volume (VT) may minimize ventilator-induced lung injury (VILI). However, atelectasis induced by low VT ventilation may cause ultrastructural evidence of cell disruption. Apoptosis seems to be involved as protective mechanisms from VILI through the involvement of mitogen-activated protein kinases (MAPKs). We examined the hypothesis that atelectasis may influence the response to protective ventilation through MAPKs. DESIGN: Prospective randomized study. SETTING: University animal laboratory. SUBJECTS: Adult male 129/Sv mice. INTERVENTIONS: Isolated, nonperfused lungs were randomized to VILI: VT of 20 mL/kg and positive end-expiratory pressure (PEEP) zero; low stretch/lung rest: VT of 6 mL/kg and 8-10 cm H2O of PEEP; low stretch/open lung: VT of 6 mL/kg, two recruitment maneuvers and 14-16 cm H2O of PEEP. Ventilator settings were adjusted using the stress index. MEASUREMENT AND MAIN RESULT: Both low stretch strategies equally blunted the VILI-induced derangement of respiratory mechanics (static volume-pressure curve), lung histology (hematoxylin and eosin), and inflammatory mediators (interleukin-6, macrophage inflammatory protein-2 [enzyme-linked immunosorbent assay], and inhibitor of nuclear factor-kB[Western blot]). VILI caused nuclear swelling and membrane disruption of pulmonary cells (electron microscopy). Few pulmonary cells with chromatin condensation and fragmentation were seen during both low stretch strategies. However, although cell thickness during low stretch/open lung was uniform, low stretch/lung rest demonstrated thickening of epithelial cells and plasma membrane bleb formation. Compared with the low stretch/open lung, low stretch/lung rest caused a significant decrease in apoptotic cells (terminal deoxynucleotidyl transferase mediated deoxyuridine-triphosphatase nick end-labeling) and tissue expression of caspase-3 (Western blot). Both low stretch strategies attenuated the activation of MAPKs. Such reduction was larger during low stretch/open lung than during low stretch/lung rest (p < 0.001). CONCLUSION: Low stretch strategies provide similar attenuation of VILI. However, low stretch/lung rest strategy is associated to less apoptosis and more ultrastructural evidence of cell damage possibly through MAPKs-mediated pathway.

Tidal volume lower than 6 ml/kg enhances lung protection: role of extracorporeal carbon dioxide removal.

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.

The effects of long-term conventional mechanical ventilation on the lungs of adult rats.

BACKGROUND: Ventilation-induced lung injury is often studied in animal models by using ventilation strategies with high-tidal volumes and high-oxygen concentration over a relatively short period of time. The injury induced by these ventilation strategies includes alterations to the surfactant system and up-regulation of inflammatory markers. Whether these responses to ventilation occur with more clinically relevant ventilation strategies is not known. OBJECTIVE: To assess how healthy adult rats respond to 24 hrs of conventional mechanical ventilation with respect to lung physiology, markers of inflammation, and alterations to pulmonary surfactant, and how this is affected by the oxygen concentration. INTERVENTIONS: Adult rats were mechanically ventilated for 24 hrs with a tidal volume of 8 mL/kg, 5 cm H2O positive end-expiratory pressure, at 60 breaths/min with either 21% or 100% oxygen. Animals were monitored for blood oxygenation and other physiologic parameters. After ventilation, lungs were lavaged and analyzed for inflammatory markers and pulmonary surfactant. These outcomes were compared with measurements obtained from spontaneously breathing rats exposed to either 21% or 100% oxygen for 24 hrs. MAIN RESULTS: Twenty-four hours of ventilation did not result in significant changes in blood oxygenation. Inflammatory markers, such as interleukin-6 concentration and the number of neutrophils in the lavage, were increased in ventilated animals compared with the nonventilated controls, regardless of the level of inspired oxygen. The amount of active surfactant was increased after ventilation; however, the surface activity of this material was impaired as compared with controls. CONCLUSION: Prolonged mechanical ventilation of health lungs with a physiologically benign strategy can contribute to the inflammatory response and cause alterations to pulmonary surfactant.

Polymyxin-B hemoperfusion inactivates circulating proapoptotic factors.

OBJECTIVE: To test the hypothesis that extracorporeal therapy with polymyxin B (PMX-B) may prevent Gram-negative sepsis-induced acute renal failure (ARF) by reducing the activity of proapoptotic circulating factors. SETTING: Medical-Surgical Intensive Care Units. PATIENTS AND INTERVENTIONS: Sixteen patients with Gram-negative sepsis were randomized to receive standard care (Surviving Sepsis Campaign guidelines) or standard care plus extracorporeal therapy with PMX-B. MEASUREMENTS AND RESULTS: Cell viability, apoptosis, polarity, morphogenesis, and epithelial integrity were evaluated in cultured tubular cells and glomerular podocytes incubated with plasma from patients of both groups. Renal function was evaluated as SOFA and RIFLE scores, proteinuria, and tubular enzymes. A significant decrease of plasma-induced proapoptotic activity was observed after PMX-B treatment on cultured renal cells. SOFA and RIFLE scores, proteinuria, and urine tubular enzymes were all significantly reduced after PMX-B treatment. Loss of plasma-induced polarity and permeability of cell cultures was abrogated with the plasma of patients treated with PMX-B. These results were associated to a preserved expression of molecules crucial for tubular and glomerular functional integrity. CONCLUSIONS: Extracorporeal therapy with PMX-B reduces the proapoptotic activity of the plasma of septic patients on cultured renal cells. These data confirm the role of apoptosis in the development of sepsis-related ARF.

Normoxic resuscitation after cardiac arrest protects against hippocampal oxidative stress, metabolic dysfunction, and neuronal death.

Resuscitation and prolonged ventilation using 100% oxygen after cardiac arrest is standard clinical practice despite evidence from animal models indicating that neurologic outcome is improved using normoxic compared with hyperoxic resuscitation. This study tested the hypothesis that normoxic ventilation during the first hour after cardiac arrest in dogs protects against prelethal oxidative stress to proteins, loss of the critical metabolic enzyme pyruvate dehydrogenase complex (PDHC), and minimizes subsequent neuronal death in the hippocampus. Anesthetized beagles underwent 10 mins ventricular fibrillation cardiac arrest, followed by defibrillation and ventilation with either 21% or 100% O2. At 1 h after resuscitation, the ventilator was adjusted to maintain normal blood gas levels in both groups. Brains were perfusion-fixed at 2 h reperfusion and used for immunohistochemical measurements of hippocampal nitrotyrosine, a product of protein oxidation, and the E1alpha subunit of PDHC. In hyperoxic dogs, PDHC immunostaining diminished by approximately 90% compared with sham-operated dogs, while staining in normoxic animals was not significantly different from nonischemic dogs. Protein nitration in the hippocampal neurons of hyperoxic animals was 2-3 times greater than either sham-operated or normoxic resuscitated animals at 2 h reperfusion. Stereologic quantification of neuronal death at 24 h reperfusion showed a 40% reduction using normoxic compared with hyperoxic resuscitation. These results indicate that postischemic hyperoxic ventilation promotes oxidative stress that exacerbates prelethal loss of pyruvate dehydrogenase and delayed hippocampal neuronal cell death. Moreover, these findings indicate the need for clinical trials comparing the effects of different ventilatory oxygen levels on neurologic outcome after cardiac arrest.

Cerebrospinal fluid from patients with subarachnoid haemorrhage and vasospasm enhances endothelin contraction in rat cerebral arteries.

INTRODUCTION: Previous studies have suggested that cerebrospinal fluid from patients with subarachnoid hemorrhage (SAH) leads to pronounced vasoconstriction in isolated arteries. We hypothesized that only cerebrospinal fluid from SAH patients with vasospasm would produce an enhanced contractile response to endothelin-1 in rat cerebral arteries, involving both endothelin ETA and ETB receptors. METHODS: Intact rat basilar arteries were incubated for 24 hours with cerebrospinal fluid from 1) SAH patients with vasospasm, 2) SAH patients without vasospasm, and 3) control patients. Arterial segments with and without endothelium were mounted in myographs and concentration-response curves for endothelin-1 were constructed in the absence and presence of selective and combined ETA and ETB receptor antagonists. Endothelin concentrations in culture medium and receptor expression were measured. RESULTS: Compared to the other groups, the following was observed in arteries exposed to cerebrospinal fluid from patients with vasospasm: 1) larger contractions at lower endothelin concentrations (p<0.05); 2) the increased endothelin contraction was absent in arteries without endothelium; 3) higher levels of endothelin secretion in the culture medium (p<0.05); 4) there was expression of ETA receptors and new expression of ETB receptors was apparent; 5) reduction in the enhanced response to endothelin after ETB blockade in the low range and after ETA blockade in the high range of endothelin concentrations; 6) after combined ETA and ETB blockade a complete inhibition of endothelin contraction was observed. CONCLUSIONS: Our experimental findings showed that in intact rat basilar arteries exposed to cerebrospinal fluid from patients with vasospasm endothelin contraction was enhanced in an endothelium-dependent manner and was blocked by combined ETA and ETB receptor antagonism. Therefore we suggest that combined blockade of both receptors may play a role in counteracting vasospasm in patients with SAH.