ARF6 is a host factor for SARS-CoV-2 infection in vitro.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged beta-coronavirus that enter cells via two routes, direct fusion at the plasma membrane or endocytosis followed by fusion with the late endosome/lysosome. While the viral receptor, ACE2, multiple entry factors and the mechanism of fusion of the virus at the plasma membrane have been investigated extensively, viral entry via the endocytic pathway is less understood. By using a human hepatocarcinoma cell line, Huh-7, which is resistant to the antiviral action of the TMPRSS2 inhibitor camostat, we discovered that SARS-CoV-2 entry is not dependent on dynamin but on cholesterol. ADP-ribosylation factor 6 (ARF6) has been described as a host factor for SARS-CoV-2 replication and is involved in the entry and infection of several pathogenic viruses. Using CRISPR/Cas9 genetic deletion, a modest reduction in SARS-CoV-2 uptake and infection in Huh-7 was observed. In addition, pharmacological inhibition of ARF6 with the small molecule NAV-2729 showed a dose-dependent reduction of viral infection. Importantly, NAV-2729 also reduced SARS-CoV-2 viral loads in more physiological models of infection: Calu-3 cells and kidney organoids. This highlighted a role for ARF6 in multiple cell contexts. Together, these experiments point to ARF6 as a putative target to develop antiviral strategies against SARS-CoV-2.

Psoriatic arthritis, axial spondyloarthritis and rheumatoid arthritis in Norway: nationwide prevalence and use of biologic agents.

OBJECTIVE: To estimate the prevalence of psoriatic arthritis (PsA), axial spondyloarthritis (axSpA) and rheumatoid arthritis (RA) and the use of biologic agents in these diseases in Norway. METHODS: From the Norwegian Patient Registry (NPR), we identified as PsA, axSpA and RA patients ≥18 years those with ≥2 recorded episodes with diagnostic coding for index disease (L40.5, M07.0-M07.3 for PsA; M45, M46.0, M46.1, M46.8 and M46.9 for axSpA; M05-M06 for RA). We calculated the point prevalence of PsA, axSpA and RA as per the 1st of January 2017 in the Norwegian adult population (age ≥18). Dispensed disease-modifying antirheumatic drug (DMARD) prescriptions were obtained from the Norwegian Prescription Database and biologic DMARDs given in hospitals from the NPR. RESULTS: The point prevalence of PsA, axSpA, RA, and any of these diseases in total was 0.46%, 0.41%, 0.78%, and 1.56%, respectively. Among women, the prevalence of PsA, axSpA, and RA was 0.50%, 0.37%, and 1.10%, and among men 0.43%, 0.45%, and 0.46%, respectively. In 2017, 27.3% of RA patients, 25.7% of PsA patients and 35.1% of axSpA patients used biologic DMARDs. Treatment with biologics was more frequent in younger age groups in all three diseases, and became more infrequent especially after age ≥55 years. CONCLUSION: In Norway, the combined prevalence of PsA, axSpA, and RA was over 1.5%. Reflecting the good overall access to highly effective but costly biologic treatments, more than a fourth of these patients used biologic agents, which corresponds to over 0.4% of Norwegian adult population.

ARF6 is a host factor for SARS-CoV-2 infection in vitro.

SARS-CoV-2 is a newly emerged beta-coronavirus that enter cells via two routes, direct fusion at the plasma membrane or endocytosis followed by fusion with the late endosome/lysosome. While the viral receptor, ACE2, multiple entry factors, and the mechanism of fusion of the virus at the plasma membrane have been extensively investigated, viral entry via the endocytic pathway is less understood. By using a human hepatocarcinoma cell line, Huh-7, which is resistant to the antiviral action of the TMPRSS2 inhibitor camostat, we discovered that SARS-CoV-2 entry is not dependent on dynamin but dependent on cholesterol. ADP-ribosylation factor 6 (ARF6) has been described as a host factor for SARS-CoV-2 replication and it is involved in the entry and infection of several pathogenic viruses. Using CRISPR-Cas9 genetic deletion, we observed that ARF6 is important for SARS-CoV-2 uptake and infection in Huh-7. This finding was corroborated using a pharmacologic inhibitor, whereby the ARF6 inhibitor NAV-2729 showed a dose-dependent inhibition of viral infection. Importantly, NAV-2729 reduced SARS-CoV-2 viral loads also in more physiologic models of infection: Calu-3 and kidney organoids. This highlighted the importance of ARF6 in multiple cell contexts. Together, these experiments points to ARF6 as a putative target to develop antiviral strategies against SARS-CoV-2.

Personal and Professional Factors Associated With Work-Life Integration Among US Physicians.

Importance: Poor work-life integration (WLI) occurs when career and personal responsibilities come in conflict and may contribute to the ongoing high rates of physician burnout. The characteristics associated with WLI are poorly understood. Objective: To identify personal and professional factors associated with WLI in physicians and identify factors that modify the association between gender and WLI. Design, Setting, and Participants: This cross-sectional study was based on electronic and paper surveys administered October 2017 to March 2018 at private, academic, military, and veteran's practices across the US. It used a population-based sample of US physicians across all medical specialties. Data analysis was performed from November 2019 to July 2020. Main Outcomes and Measures: WLI was assessed using an 8-item scale (0-100 point scale, with higher scores indicating favorable WLI), alongside personal and professional factors. Multivariable linear regressions evaluated independent associations with WLI as well as factors that modify the association between gender and WLI. Results: Of 5197 physicians completing surveys, 4370 provided complete responses. Of the physicians who provided complete responses, 2719 were men, 3491 were White/Caucasian (80.8%), 3560 were married (82.4%), and the mean (SD) age was 52.3 (12.0) years. The mean (SD) WLI score was 55 (23). Women reported lower (worse) mean (SD) WLI scores than men overall (52 [22] vs 57 [23]; mean difference, -5 [-0.2 SDs]; P < .001). In multivariable regression, lower WLI was independently associated with being a woman (linear regression coefficient, -6; SE, 0.7; P < .001) as well as being aged 35 years or older (eg, aged 35 to 44 years: linear regression coefficient, -7; SE, 1.4; P < .001), single (linear regression coefficient, -3 vs married; SE, 1.1; P = .003), working more hours (eg, 50 to 59 hours per week vs less than 40 hours per week: linear regression coefficient, -9; SE, 1.0; P < .001) and call nights (linear regression coefficient, -1 for each call night per week; SE, 0.2; P < .001), and being in emergency medicine (linear regression coefficient, -18; SE, 1.6, P < .001), urology (linear regression coefficient, -11; SE, 4.0; P = .009), general surgery (linear regression coefficient, -4; SE, 2.0; P = .04), anesthesiology (linear regression coefficient, -4; SE, 1.7; P = .03), or family medicine (linear regression coefficient, -3; SE, 1.4; P = .04) (reference category, internal medicine subspecialties). In interaction modeling, physician age, youngest child's age, and hours worked per week modified the associations between gender and WLI, such that the largest gender disparities were observed in physicians who were aged 45 to 54 years (estimated WLI score for women, 49; 95% CI, 47-51; estimated WLI score for men, 57, 95% CI, 55-59; P < .001), had youngest child aged 23 years or older (estimated WLI score for women, 51; 95% CI, 48-54; estimated WLI score for men, 60; 95% CI, 58-62; P < .001), and were working less than 40 hours per week (estimated WLI score for women, 61; 95% CI, 59-63; estimated WLI score for men; 70; 95% CI, 68-72; P < .001). Conclusions and Relevance: This study found that lower WLI was reported by physicians who are women, single, aged 35 years or older, and who work more hours and call nights. These findings suggest that systemic change is needed to improve WLI among physicians.

Serum golimumab concentration and anti-drug antibodies are associated with treatment response and drug survival in patients with inflammatory joint diseases: data from the NOR-DMARD study.

Objectives: This study aimed to identify the therapeutic target concentration and frequency of anti-drug antibodies (ADAbs) in golimumab-treated patients with inflammatory joint disease (IJD).Method: Associations between golimumab concentration, ADAbs, and treatment response were examined in 91 patients with IJD [41 axial spondyloarthritis (axSpA), 20 rheumatoid arthritis (RA), and 30 psoriatic arthritis (PsA)] included in the NOR-DMARD study. Treatment response was defined by Ankylosing Spondylitis Disease Activity Score (ASDAS) clinically important improvement in axSpA, European League Against Rheumatism (EULAR) good/moderate response in RA, and improvement of ≥ 50% in modified Disease Activity index for PSoriatic Arthritis (DAPSA) (28 swollen/tender joint counts) in PsA. Serum drug concentrations and ADAbs were analysed using automated in-house assays.Results: At inclusion, 42% were biological disease-modifying anti-rheumatic drug naïve and 42% used concomitant synthetic disease-modifying anti-rheumatic drug. The median golimumab concentration was 2.2 (interquartile range 1.0-3.5) mg/L. The proportions of responders after 3 months among patients with golimumab concentration < 1.0, 1.0-3.9, and ≥ 4.0 mg/L were 19%, 49%, and 74%, respectively. A higher rate of treatment discontinuation was seen in patients with serum golimumab concentration < 1.0 compared to ≥ 1.0 mg/L (hazard ratio 3.3, 95% confidence interval 1.8-6.0, p < 0.05). ADAbs were detected in 6%, and were associated with lower drug concentrations and both reduced treatment response and drug survival.Conclusions: Golimumab concentrations ≥ 1.0 mg/L were associated with improved treatment response and better drug survival, although some patients may benefit from higher concentrations. This study suggests a rationale for dosing guided by therapeutic drug monitoring in golimumab-treated patients with IJD. The results should be confirmed in larger studies including trough samples, and the efficacy of such a strategy must be examined in randomized controlled trials.

Histologic and Immunohistochemical Analyses of Soft Tissue Sarcomas From brca2-Mutant/ tp53-Mutant Zebrafish Are Consistent With Neural Crest (Schwann Cell) Origin.

The zebrafish ( Danio rerio) provides a powerful model for analyzing genetic contributors to cancer. Multiple zebrafish lines with cancer-associated genetic mutations develop soft tissue sarcomas that are histologically consistent with malignant peripheral nerve sheath tumor (MPNST). The goal of this study was to determine the phenotype of soft tissue sarcomas in a brca2-mutant/ tp53-mutant zebrafish line using immunohistochemical markers that are commonly expressed in mammalian MPNST. We classified 70 soft tissue sarcomas from a brca2-mutant/ tp53-mutant zebrafish cohort as MPNST, undifferentiated sarcoma, or other tumor based on histologic features. The expression of S100, CD57, and glial fibrillary acidic protein (GFAP) was analyzed in nonneoplastic neural tissues and tumor specimens by immunohistochemistry. Each marker was expressed in nonneoplastic neural tissues. In MPNST, S100 and CD57 were widely expressed in neoplastic cells, with greater consistency observed for CD57 expression. In undifferentiated sarcomas, results were variable and correlated to anatomic location. Coelomic undifferentiated sarcomas often exhibited widespread CD57 expression but limited S100 expression. In comparison, ocular undifferentiated sarcomas exhibited limited expression of both CD57 and S100. Overall, CD57 and S100 expression was significantly higher in MPNST than in undifferentiated sarcomas. GFAP was not expressed in any of the tumors. This study identified commercially available antibodies that are useful for analyzing S100, CD57, and GFAP expression in zebrafish. This study further shows a correlation between degree of histologic differentiation and expression of these markers in soft tissue sarcomas from brca2-mutant/ tp53-mutant zebrafish and suggests that these cancers are derived from the neural crest with differentiation toward myelinating Schwann cells.

A closer look at associations between hospital leadership walkrounds and patient safety climate and risk reduction: a cross-sectional study.

Leadership walkrounds (WRs) are widely used in health care organizations to improve patient safety. This retrospective, cross-sectional study evaluated the association between WRs and caregiver assessments of patient safety climate and patient safety risk reduction across 49 hospitals in a nonprofit health care system. Linear regression analyses using units' participation in WRs were conducted. Survey results from 706 hospital units revealed that units with ≥ 60% of caregivers reporting exposure to at least 1 WR had a significantly higher safety climate, greater patient safety risk reduction, and a higher proportion of feedback on actions taken as a result of WRs compared with those units with <60% of caregivers reporting exposure to WRs. WR participation at the unit level reflects a frequency effect as a function of units with none/low, medium, and high leadership WR exposure.

Beneficial effects of polyphenol-rich olive oil in patients with early atherosclerosis.

PURPOSE: Diets rich in plant-derived polyphenols such as olive oil (OO) and/or catechins such as epigallocatechin 3-gallate (EGCG) have been shown to reduce the incidence of cardiovascular diseases, potentially by improving endothelial function, an important surrogate for atherosclerosis. The possible augmentation of endothelial function with the combined efforts of OO and EGCG is intriguing, yet unknown. METHODS: Eighty-two patients with early atherosclerosis (presence of endothelial dysfunction) were enrolled in this double-blind, randomized trial with 52 completing the study. The aim of the study was to compare the effect of a daily intake of 30 ml simple OO, with 30 ml of EGCG-supplemented OO, on endothelial function as well as on inflammation and oxidative stress after a period of 4 months. Endothelial function was assessed noninvasively via peripheral arterial tonometry (Endo-PAT®). RESULTS: After 4 months, when OO and EGCG-supplemented OO groups were combined, OO significantly improved endothelial function (RHI, 1.59 ± 0.25-1.75 ± 0.45; p < 0.05). However, there were no significant differences in results between the two olive oil groups. Interestingly, with OO supplementation there was a significant reduction in inflammatory parameters: sICAM (196 to 183 ng/mL, p = < 0.001); white blood cells (WBCs) (6.0 × 109/L-5.8 × 109/L, p < 0.05); monocytes (0.48 × 109/L to 0.44 × 109/L, p = 0.05); lymphocytes (1.85 × 109/L to 1.6 × 109/L, p = 0.01); and platelets (242-229 × 109/L, p = 0.047). CONCLUSIONS: Improvement in endothelial dysfunction in patients with early atherosclerosis in association with significant reduction in leukocytes may suggest an important role of early cellular inflammatory mediators on endothelial function. The current study supports one potential mechanism for the role of olive oil, independent of EGCG, modestly supplemented to a healthy cardiovascular diet.

Targeting GLI1 expression in human inflammatory breast cancer cells enhances apoptosis and attenuates migration.

BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive subtype of breast cancer with distinct molecular profiles. Gene expression profiling previously identified sonic hedgehog (SHH) as part of a gene signature that is differentially regulated in IBC patients. METHODS: The effects of reducing GLI1 levels on protein expression, cell proliferation, apoptosis and migration were determined by immunoblots, MTT assay, Annexin-V/PI assay and conventional and automated cell migration assays. RESULTS: Evaluation of a panel of breast cancer cell lines revealed elevated GLI1 expression, typically a marker for hedgehog-pathway activation, in a triple-negative, highly invasive IBC cell line, SUM149 and its isogenic-derived counterpart rSUM149 that has acquired resistance to ErbB1/2 targeting strategies. Downregulation of GLI1 expression in SUM149 and rSUM149 by small interfering RNA or a small molecule GLI1 inhibitor resulted in decreased proliferation and increased apoptosis. Further, GLI1 suppression in these cell lines significantly inhibited cell migration as assessed by a wound-healing assay compared with MCF-7, a non-invasive cell line with low GLI1 expression. A novel high-content migration assay allowed us to quantify multiple effects of GLI1 silencing including significant decreases in cell distance travelled and linearity of movement. CONCLUSION: Our data reveal a role for GLI1 in IBC cell proliferation, survival and migration, which supports the feasibility of targeting GLI1 as a novel therapeutic strategy for IBC patients.

Cancer family history characterization in an unselected cohort of 121 patients with uveal melanoma.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. The extent of the contribution of familial/hereditary predisposition to the development of uveal melanoma is largely unknown. Thus we sought to ascertain the frequency of cancers in patients with UM and their family members to identify the prevalence of hereditary/familial predisposition to cancer in these patients. An unselected series of 121 patients with UM seen in a university-based tertiary referral program were consented to the study. Cancer histories (site and age of diagnosis) were obtained for all first- and second-degree relatives. Patients/families were classified as being potentially at high risk for hereditary predisposition if they met any of the following criteria: (1) Diagnosis of UM at age 30 or under, (2) Two or more cases of UM in the family, (3) UM plus at least one other primary cancer in the same patient (excluding non-melanoma skin and cervix cancers due to their strong environmental etiological link). (4) Family history meeting high risk criteria for a known hereditary cancer predisposition syndrome as defined by Hampel et al. (J Med Genet 41(2): 81-91, 2004). One patient had a family history of UM (0.8%). Ten patients (8.3%) had a personal and/or family history consistent with predisposition to a known hereditary cancer syndrome including six with possible hereditary breast, two with hereditary colon and two with hereditary melanomas. Twenty three patients (19%) had a personal history of a second cancer after exclusion of non-melanoma skin and cervical cancers. The frequency of cutaneous melanomas was significantly higher in UM patients than the general population (RR: 2.97, 95% CI: 1.00-6.94). Patients with a family history suggestive of a high risk predisposition to a known cancer syndrome had a significantly higher risk for having a second cancer than the remaining UM patients (P = 0.02). Our results indicate that the frequency of UM patients with high risk for a hereditary cancer predisposition is much higher than earlier estimates (0.6%) and that it could be as high as 11.6%. Our results suggest that cancer phenotypes in these patients are diverse and include cancers other than UM. Thus, alerting ophthalmologists to the need for expanding their cancer family history intake to include other cancers is warranted. It also suggests that patients with a hereditary predisposition to UM have a higher risk for the development of other cancers and that characterization of the germline genetic alterations in these patients is highly warranted.

Reducing health care hazards: lessons from the commercial aviation safety team.

The movement to improve quality of care and patient safety has grown, but examples of measurable and sustained progress are rare. The slow progress made in health care contrasts with the success of aviation safety. After a tragic 1995 plane crash, the aviation industry and government created the Commercial Aviation Safety Team to reduce fatal accidents. This public-private partnership of safety officials and technical experts is responsible for the decreased average rate of fatal aviation accidents. We propose a similar partnership in the health care community to coordinate national efforts and move patient safety and quality forward.

Measurement of quality and assurance of safety in the critically ill.

The global health care community has worked tirelessly for nearly a decade to make medical care safer for patients, but it still has limited ability to evaluate whether safety has improved. While there is a universal push to measure safety outcomes, the main barrier has been poor investment in the basic science of patient safety. This science would allow us to comprehend the causes of harm, design and pilot test interventions to reduce harm, and robustly evaluate their impact. This article describes several dilemmas in measuring patient safety, outlines a conceptual model and presents a framework for measuring patient safety, and offers future directions. Future research should seek to create a scientifically sound and feasible safety scorecard and improve performance.

Surgical team behaviors and patient outcomes.

BACKGROUND: Little evidence exists that links teamwork to patient outcomes. We conducted this study to determine if patients of teams with good teamwork had better outcomes than those with poor teamwork. METHODS: Observers used a standardized instrument to assess team behaviors. Retrospective chart review was performed to measure 30-day outcomes. Multiple logistic regressions were calculated to assess the independence of the association between teamwork with patient outcome after adjusting for American Society of Anesthesiologists (ASA) score. RESULTS: In univariate analyses, patients had increased odds of complications or death when the following behaviors were exhibited less frequently: information sharing during intraoperative phases, briefing during handoff phases, and information sharing during handoff phases. Composite measures of teamwork across all operative phases were significantly associated with complication or death after adjusting for ASA score (odds ratio 4.82; 95% confidence interval, 1.30-17.87). CONCLUSION: When teams exhibited infrequent team behaviors, patients were more likely to experience death or major complication.

Impact of preoperative briefings on operating room delays: a preliminary report.

HYPOTHESIS: Preoperative briefings have the potential to reduce operating room (OR) delays through improved teamwork and communication. DESIGN: Pre-post study. SETTING: Tertiary academic center. PARTICIPANTS: Surgeons, anesthesiologists, nurses, and other OR personnel. INTERVENTION: An OR briefings program was implemented after training all OR staff in how to conduct preoperative briefings through in-service training sessions. During the preoperative briefings, the attending surgeon led OR personnel in a 2-minute discussion using a standardized format designed to familiarize caregivers with each other and the operative plan before each surgical procedure. MAIN OUTCOME MEASURES: The OR Briefings Assessment Tool was distributed to OR personnel at the end of each operation. Survey items questioned OR personnel about unexpected delays during each procedure and the relationship between communication breakdowns and delays. Responses were compared before and after the initiation of the preoperative briefings program. RESULTS: The use of preoperative briefings was associated with a 31% reduction in unexpected delays; 36% of OR personnel reported delays in the preintervention period, and 25% reported delays in the postintervention period (P<.04). Among surgeons alone, an 82% reduction in unexpected delays was observed (P<.001). A 19% reduction in communication breakdowns leading to delays was also associated with the use of briefings (P<.006). CONCLUSIONS: Preoperative briefings reduced unexpected delays in the OR by 31% and decreased the frequency of communication breakdowns that lead to delays. Preoperative briefings have the potential to increase OR efficiency and thereby improve quality of care and reduce cost.

Developing process-support tools for patient safety: finding the balance between validity and feasibility.

The Johns Hopkins Quality and Safety Research Group, which has developed many process-support tools--three of which are reported in this issue--describes its approach to tool development.

Measuring safety culture in the ambulatory setting: the safety attitudes questionnaire--ambulatory version.

BACKGROUND: Provider attitudes about issues pertinent to patient safety may be related to errors and adverse events. We know of no instruments that measure safety-related attitudes in the outpatient setting. OBJECTIVE: To adapt the safety attitudes questionnaire (SAQ) to the outpatient setting and compare attitudes among different types of providers in the outpatient setting. METHODS: We modified the SAQ to create a 62-item SAQ-ambulatory version (SAQ-A). Patient care staff in a multispecialty, academic practice rated their agreement with the items using a 5-point Likert scale. Cronbach's alpha was calculated to determine reliability of scale scores. Differences in SAQ-A scores between providers were assessed using ANOVA. RESULTS: Of the 409 staff, 282 (69%) returned surveys. One hundred ninety (46%) surveys were included in the analyses. Cronbach's alpha ranged from 0.68 to 0.86 for the scales: teamwork climate, safety climate, perceptions of management, job satisfaction, working conditions, and stress recognition. Physicians had the least favorable attitudes about perceptions of management while managers had the most favorable attitudes (mean scores: 50.4 +/- 22.5 vs 72.5 +/- 19.6, P < 0.05; percent with positive attitudes 18% vs 70%, respectively). Nurses had the most positive stress recognition scores (mean score 66.0 +/- 24.0). All providers had similar attitudes toward teamwork climate, safety climate, job satisfaction, and working conditions. CONCLUSION: The SAQ-A is a reliable tool for eliciting provider attitudes about the ambulatory work setting. Attitudes relevant to medical error may differ among provider types and reflect behavior and clinic operations that could be improved.

Operating room briefings and wrong-site surgery.

BACKGROUND: Wrong-site surgery can be a catastrophic event for a patient, caregiver, and institution. Although communication breakdowns have been identified as the leading cause of wrong-site surgery, the efficacy of preventive strategies remains unknown. This study evaluated the impact of operating room briefings on coordination of care and risk for wrong-site surgery. STUDY DESIGN: We administered a case-based version of the Safety Attitudes Questionnaire (SAQ) to operating room (OR) staff at an academic medical center, before and after initiation of an OR briefing program. Items questioned overall coordination and awareness of the surgical site. Response options ranged from 1 (disagree strongly) to 5 (agree strongly). MANOVA was used to compare caregiver assessments before and after the implementation of briefings, and the percentage of OR staff agreeing or disagreeing with each question was reported. RESULTS: The prebriefing response rate was 85% (306 of 360 respondents), and the postbriefing response rate was 75% (116 of 154). Respondents included surgeons (34.9%), anesthesiologists (14.0%), and nurses (44.4%). Briefings were associated with caregiver perceptions of reduced risk for wrong-site surgery and improved collaboration [F (6,390)=10.15, p < 0.001]. Operating room caregiver assessments of briefing and wrong-site surgery issues improved for 5 of 6 items, eg, "Surgery and anesthesia worked together as a well-coordinated team" (67.9% agreed prebriefing, 91.5% agreed postbriefing, p < 0.0001), and "A preoperative discussion increased my awareness of the surgical site and side being operated on" (52.4% agreed prebriefing, 64.4% agreed postbriefing, p < 0.001). CONCLUSIONS: OR briefings significantly reduce perceived risk for wrong-site surgery and improve perceived collaboration among OR personnel.

Toward learning from patient safety reporting systems.

PURPOSE: To evaluate the frequency and type of factors involved in incidents reported to a patient safety reporting system and answer specific questions to enhance the value of PSRS data to improve patient safety. MATERIALS AND METHODS: Prospective cohort study of incidents reported from adult and pediatric intensive care units (ICUs) in the United States to the web-based, voluntary, and anonymous Intensive Care Unit Safety Reporting System. Results from July 1, 2002, to June 30, 2004. Main outcome variables were incidents that could or did lead to patient harm. RESULTS: Analysis includes 2075 incidents from 23 ICUs. Median number of reports/ICU/month was 3; 5 hospitals submitted 58% of reports. Harm was reported in 42% of incidents with 18 deaths. Common event types: medication/therapeutics (42%) and incorrect/incomplete care delivery (20%); 48% of line/tube/drain incidents led to physical harm. Deficiencies in training/education contributed to 49% of incidents and teamwork issues 32%; 42% of incidents had 2 or more contributing factors. As the number of contributing factors per incident increased, so did risk of harm. CONCLUSIONS: The Intensive Care Unit Safety Reporting System provides a mechanism for multiple ICUs to identify hazards. Data trends show a correlation between multiple contributing factors and higher rates of harm. Further research is needed to help determine how to use PSRS data to improve patient safety.

Operating room debriefings.

This tool helps assess factors that positively and negatively contributed to an adverse event, near miss, or inefficiency during an operation-or any procedure.