Root Cause Analysis of Delayed Emergency Department Computed Tomography Scans.

Introduction: A solution for emergency department (ED) congestion remains elusive. As reliance on imaging grows, computed tomography (CT) turnaround time has been identified as a major bottleneck. In this study we sought to identify factors associated with significantly delayed CT in the ED. Methods: We performed a retrospective analysis of all CT imaging completed at an urban, tertiary care ED from May 1-July 31, 2021. During that period, 5,685 CTs were performed on 4,344 patients, with a median time from CT order to completion of 108 minutes (Quartile 1 [Q1]: 57 minutes, Quartile 3 [Q3]: 182 minutes, interquartile range [IQR]: 125 minutes). Outliers were defined as studies that took longer than 369 minutes to complete (Q3 + 1.5 × IQR). We systematically reviewed outlier charts to determine factors associated with delay and identified five factors: behaviorally non-compliant or medically unstable patients; intravenous (IV) line issues; contrast allergies; glomerular filtration rate (GFR) concerns; and delays related to imaging protocol (eg, need for IV contrast, request for oral and/or rectal contrast). We calculated confidence intervals (CI) using the modified Wald method. Inter-rater reliability was assessed with a kappa analysis. Results: We identified a total of 182 outliers (4.2% of total patients). Fifteen (8.2%) cases were excluded for CT time-stamp inconsistencies. Of the 167 outliers analyzed, 38 delays (22.8%, 95% confidence interval [CI] 17.0-29.7) were due to behaviorally non-compliant or medically unstable patients; 30 (18.0%, 95% CI 12.8-24.5) were due to IV issues; 24 (14.4%, 95% CI 9.8-20.6) were due to contrast allergies; 21 (12.6%, 95% CI 8.3-18.5) were due to GFR concerns; and 20 (12.0%, 95% CI 7.8-17.9) were related to imaging study protocols. The cause of the delay was unknown in 55 cases (32.9%, 95% CI 26.3-40.4). Conclusion: Our review identified both modifiable and non-modifiable factors associated with significantly delayed CT in the ED. Patient factors such as behavior, allergies, and medical acuity cannot be controlled. However, institutional policies regarding difficult IV access, contrast administration in low GFR settings, and study protocols may be modified, capturing up to 42.6% of outliers.

[Implementation and Effectiveness of Measures to Prevent Recurrence of Incidents Developed through Root Cause Analysis Using Work Flowchart].

PURPOSE: Incidents are recommended to be analyzed by root cause analysis (RCA). Our institution also conducts RCA for incidents and takes measures to prevent recurrence. The purpose of this study was to evaluate the effectiveness of countermeasures against the root causes analyzed by RCA in order to prevent recurrence of incidents. METHODS: Since the treatment planning CT scanner was replaced, incidents of failure to zero adjustment the coordinates of the bed position occurred four times during a three-month period. The RCA was used to investigate the root causes of these incidents and to formulate measures to prevent recurrence. To evaluate the effectiveness of the recurrence prevention measures, we collected the number of recurrence of incidents during the first year after the effectiveness of the recurrence prevention measures, and used the chi-square test to determine the significant difference in the probability of an incident occurring at a significance level of 5% or less. RESULTS: The measures to prevent the recurrence of incidents were to double-check that the coordinates of the bed position were adjusted to zero and to simulate operations based on a work flow that incorporated this double-check. During the first year period following the implementation of these recurrence prevention measures, the number of recurrence incidents was zero, and the probability of their occurrence decreased statistically significantly (p<0.05). CONCLUSION: Thorough double-checks and work simulation based on the work flow are effective methods for preventing the recurrence of incidents.

Learning from Non-Routine Events and Teamwork in Intensive Care Units: Challenges and Opportunities.

Patients admitted to intensive care units (ICUs) have profound and complex illnesses, often fraught with uncertainties in diagnoses, treatments, and care decisions. Clinicians often deviate from best practices to handle ICUs' myriad complexities and uncertainties. Non-routine events (NREs), defined as any aspect of care perceived by clinicians as deviations from optimal care, are latent and frequent safety threats that, if left unchecked, can be precursors to adverse events. Proper identification and analysis of NREs that represent latent safety threats have been proposed as a feasible and more effective approach for performance improvement than traditional root cause analysis for patient safety events. However, NRE studies to date have yet to show the holistic picture of NREs in the contexts of teamwork and time-dependent tasks that are frequently associated with NREs. NREs, an upstream interventional area to understand root causes, team performance, and human-computer interaction, still needs to be expanded. This article presents concepts of NREs, and the use of real-world data (RWD) and informatics methodology to investigate NREs in contexts and discusses the opportunities and challenges to enhance NREs research in teamwork and time-dependent tasks.

Root cause analysis of medication errors of the most frequently involved active substances in paediatric patients.

BACKGROUND: Use of medicinal products in paediatric patients is identified as a risk factor for the occurrence of medication errors. OBJECTIVES: To describe and identify root causes of medication errors in children and adolescents spontaneously reported to Agency for Medicinal Products and Medical Devices of Croatia (Agency). METHOD: Agency's adverse drug reaction database was searched by using the Standardised MedDRA Query: medication errors (Broad) with data lock point set at 30th June 2022. Cases in which medication errors occurred in patients up to 18 years of age were analysed according to the patients' age group and gender, reporter's qualification, seriousness, reported preferred terms and active substances. For the first 30 most frequently reported active substances, an in-depth analysis was performed to identify the root cause of medication errors. RESULTS: Altogether, 6254 reports were spontaneously reported to the Agency, out of which 1947 (31 %) contained at least one preferred term belonging to Standardised MedDRA Query medication errors. More than half of patients experiencing medication errors belonged to the age group 2-11 years (66 %) and male gender (53 %). The most frequently reported ME PTs included accidental exposure to product by a child (64 %) and accidental overdose (17 %). Medication error root causes for the first 30 most frequently involved active substances included misinterpretation of prescribed dosage due to a very small volume resulting in salbutamol overdose; replacing millilitre and milligram units resulting in paracetamol solution overdose; interchange between medicinal products due to primary package similarities resulting in cholecalciferol overdose and interchange between oral solution and syrup resulting in valproate overdose. CONCLUSIONS: Healthcare professionals should counsel caregivers about the importance of keeping medicinal products out of children's reach and provide detailed instructions on how to appropriately use medicinal products.

Team experiences of the root cause analysis process after a sentinel event: a qualitative case study.

BACKGROUND: Root cause analysis (RCA) is a systematic approach, typically involving several stages, used in healthcare to identify the underlying causes of a medical error or sentinel event. This study focuses on how members of a Norwegian RCA team experience aspects of an RCA process and whether it complies with the Norwegian RCA method. METHOD: Based on a sentinel event in which a child died unexpectedly during childbirth in a Norwegian hospital in 2021, the following research questions are addressed: 1. What was the RCA team's experience of the RCA process? 2. Was there compliance with the Norwegian RCA method in this case? A case study was chosen out of the desire to understand complex social phenomena and to allow in-depth focus on a case. RESULTS: The result covered three main themes. The first theme related to the hospital's management system and aspects of the case that made it challenging to follow all recommendations in the Norwegian RCA guidelines. The second theme encompassed external and internal assessment. The RCA team was composed of members with methodological and medical expertise. However, the police's involvement in the case made it complex for the team to carry out the process. The third and final theme covered intrapersonal challenges RCA team members faced. Team members experienced various challenges during the RCA process, including being neutral, dealing with role-related challenges, grappling with ambivalence, and managing the additional time burden and resource constraints. As anticipated in the RCA guidelines, the team's ability to remain neutral was tested. CONCLUSION: The findings of this study can help stakeholders better comprehend how an inter-professional RCA teamwork intervention can affect a healthcare organization and enhance the teamwork experience of healthcare staff while facilitating improvements in work processes and patient safety. Additionally, these results can guide stakeholders in creating, executing, utilizing, and educating others about RCA processes.

Characterization and root cause analysis of immunogenicity to pasotuxizumab (AMG 212), a prostate-specific membrane antigen-targeting bispecific T-cell engager therapy.

Introduction: In oncology, anti-drug antibody (ADA) development that significantly curtails response durability has not historically risen to a level of concern. The relevance and attention ascribed to ADAs in oncology clinical studies have therefore been limited, and the extant literature on this subject scarce. In recent years, T cell engagers have gained preeminence within the prolific field of cancer immunotherapy. These drugs whose mode of action is expected to potently stimulate anti-tumor immunity, may potentially induce ADAs as an unintended corollary due to an overall augmentation of the immune response. ADA formation is therefore emerging as an important determinant in the successful clinical development of such biologics. Methods: Here we describe the immunogenicity and its impact observed to pasotuxizumab (AMG 212), a prostate-specific membrane antigen (PSMA)-targeting bispecific T cell engager (BiTE®) molecule in NCT01723475, a first-in-human (FIH), multicenter, dose-escalation study in patients with metastatic castration-resistant prostate cancer (mCRPC). To explain the disparity in ADA incidence observed between the SC and CIV arms of the study, we interrogated other patient and product-specific factors that may have explained the difference beyond the route of administration. Results: Treatment-emergent ADAs (TE-ADA) developed in all subjects treated with at least 1 cycle of AMG 212 in the subcutaneous (SC) arm. These ADAs were neutralizing and resulted in profound exposure loss that was associated with contemporaneous reversal of initial Prostate Surface Antigen (PSA) responses, curtailing durability of PSA response in patients. Pivoting from SC to a continuous intravenous (CIV) administration route remarkably yielded no subjects developing ADA to AMG 212. Through a series of stepwise functional assays, our investigation revealed that alongside a more historically immunogenic route of administration, non-tolerant T cell epitopes within the AMG 212 amino acid sequence were likely driving the high-titer, sustained ADA response observed in the SC arm. Discussion: These mechanistic insights into the AMG 212 ADA response underscore the importance of performing preclinical immunogenicity risk evaluation as well as advocate for continuous iteration to better our biologics.

What are the experiences of team members involved in root cause analysis? A qualitative study.

BACKGROUND: Conducting root cause analysis (RCA) is complex and challenging. The aim of this study was to better understand the experiences of RCA team members and how they value their involvement in the RCA to inform future recruitment, conduct and implementation of RCA findings into clinical practice. METHODS: The study was set in a health network in Adelaide, South Australia. A qualitative exploratory descriptive approach was undertaken to provide an in-depth understanding of team member's experience in participating in an RCA. Eight of 27 RCA team members who conducted RCAs in the preceding 3-year period were included in one of three semi-structured focus groups. Thematic analysis was used to synthesise the transcribed data into themes. RESULTS: We derived four major themes: Experiences and perceptions of the RCA team, Limitations of RCA recommendations, Facilitators and barriers to conducting an RCA, and Supporting colleagues involved in the adverse event. Participants' mixed experience of RCAs ranged from enjoyment and the perception of worth and value to concerns about workload and lack of impact. Legislative privilege protecting RCAs from disclosure was both a facilitator and a barrier. Concern and a desire to better support their colleagues was widely reported. CONCLUSIONS: Clinicians perceived value in reviewing significant adverse events. Improvements can be made in sharing learnings to make effective improvements in health care. We have proposed a process to better support interviewees and strengthen post interview follow up.

Root Cause Analysis of An Inverse Relationship Between The Ice Nucleation Temperature, Process Efficiency And Quality of A Lyophilized Product.

The aim of this study was to probe an unexpected relationship between the ice nucleation temperature (TIN), process efficiency and product attributes in a controlled ice nucleation (CIN) lyophilization process. An amorphous product was lyophilized with (CIN-5 °C, CIN-7 °C or CIN-10 °C) or without (NOCIN) control of ice nucleation. Process parameters and product attributes were monitored and compared using a series of advanced in-line and off-line process analytical technology (PAT) tools. Unexpectedly, an indirect relationship was observed between TIN and primary drying efficiency for the CIN processes. Further, the CIN-5 °C process was associated with higher product resistance to mass flow than corresponding CIN-7 °C and CIN-10 °C processes. Surprisingly, the air voids in some NOCIN products were larger than CIN-5 °C products but comparable to CIN-7 °C. Heat flux analysis revealed an indirect relationship between TIN and the minimum hold time required to complete solidification. The heat flux analysis also revealed all products underwent complete solidification prior to primary drying. The order of homogeneity in water activity of the products was CIN-5 °C ≥NOCIN>CIN-7 °C. The higher homogeneity in water activity of CIN-5 °C than corresponding CIN-7 °C processes indicated that the lower process efficiency of CIN-5 °C could not be attributed to unsuccessful induction of ice nucleation during CIN-5 °C. High resolution micro-CT imaging and Artificial Intelligence Image analysis revealed cake wall deformation in CIN-7 °C and NOCIN products but not in CIN-5 °C. In addition, NOCIN products had bimodal distribution in air voids with median size range of 4-5 µm and 151.9-309 µm, respectively, hence the lower process efficiency of NOCIN despite the higher D90. Thus, the observed relationship between TIN and process efficiency may be attributed to microstructural changes post freezing. This hypothesis was corroborated by visible macroscopic cake collapse in NOCIN products but not in CIN products after lyophilization at a higher shelf temperature. In conclusion, the advantages of controlling the ice nucleation temperature of a lyophilization process may only be attained through a robust process design that takes into consideration the primary and secondary drying process parameters. Further, combined use of advanced in-line and off-line PAT tools for process and product characterization may hasten the at scale adoption of advance techniques such as CIN.

Qualitative study on experience of healthcare staff who have undergone a hybrid root cause analysis training programme.

BACKGROUND: Root cause analysis (RCA) is a structured investigation methodology aimed at identifying systems factors to prevent recurrence of incidents. To enhance staff's knowledge and skills, a hybrid RCA training course was conducted in February 2021. Overseas instructors conducted training online and local participants attended the training together physically with onsite facilitator support. This study aimed at understanding the experiences of trainees who have undergone the training, evaluated its effectiveness and identified opportunities to enhance RCA training quality in the future. METHODS: A qualitative study using virtual synchronous focus group interviews was conducted. Purposive sampling was adopted to invite all trainees from the RCA training course to join. A semistructured interview was used to guide the study participants to share their experiences. All groups were audio-recorded, transcribed verbatim and anonymised for data analysis. RESULTS: Overall, 6 focus groups with 19 participants were held between July and November 2021. Five key themes were identified including: (1) training contents, (2) perceptions of RCA, (3) challenges in RCA, (4) hybrid training and (5) future perspectives. Participants felt the RCA training was useful and broadened their understanding in incident investigation. More in-depth training in interviewing skills, report writing with practical sessions could further enhance their competencies in RCA. Participants accepted the use of hybrid online-offline training well. Most participants would welcome an independent organisation to conduct RCA as findings would be more objective and recommendations more effective. CONCLUSIONS: This study provided an evaluation on the effectiveness of a hybrid RCA training course. Healthcare and training organisations can consider this training mode as it could reduce the cost of training and enhance flexibility in course arrangement while preserving quality and effectiveness. Virtual focus groups to interview participants were found to be convenient as it minimised travelling time and onsite arrangement while maintaining the quality of discussion.

Investigation of urology intraoperative events leading to root cause analysis at national VA medical centers.

INTRODUCTION: Adverse events in urologic procedures are poorly studied. This study analyzes the Veterans Health Administration (VHA) Root Cause Analysis (RCA) data for patient safety adverse events during urologic procedures performed in a VHA operating room (OR). MATERIALS AND METHODS: The VHA National Center for Patient Safety RCA database was queried for fiscal years 2015-2019 using urologic terms including vasectomy, prostatectomy, nephrectomy, cystectomy, cystoscopy, lithotripsy, ureteroscopy, urethral, TURBT, etc. RCAs for events outside a VHA OR were excluded. Cases were categorized based on type of event. RESULTS: Sixty-eight RCAs were identified for 319,713 urologic procedures. The most common pattern identified was equipment or instrument issue, including broken scopes or smoking light cords, with 22 cases. Eighteen RCAs involved a sentinel event, including 12 retained surgical items (RSI) (surgical sponge, retained guidewire) and 6 wrong site surgeries (WSS) (incorrect laterality, wrong procedure) representing a serious safety event rate of 1 in 17,762 procedures. In addition, 8 RCAs pertained to medical or anesthesia events (incorrect dosing, postoperative myocardial infarction), 7 to pathology errors (missing or mislabeled specimen), 4 to incorrect patient information or consent, and 4 to surgical complications (hemorrhage, duodenal injury). In 2 cases there was inappropriate work up. One case caused a delay in treatment, one case had an incorrect count, and one case identified lack of credentialing. CONCLUSIONS: RCAs of patient safety adverse events occurring during urologic OR procedures highlight the need for targeted quality improvement projects to prevent WSS events, prevent RSI events, and maintain properly functioning equipment.

Identifying Contributing Factors Associated With Dental Adverse Events Through a Pragmatic Electronic Health Record-Based Root Cause Analysis.

OBJECTIVE: This study assessed contributing factors associated with dental adverse events (AEs). METHODS: Seven electronic health record-based triggers were deployed identifying potential AEs at 2 dental institutions. From 4106 flagged charts, 2 reviewers examined 439 charts selected randomly to identify and classify AEs using our dental AE type and severity classification systems. Based on information captured in the electronic health record, we analyzed harmful AEs to assess potential contributing factors; harmful AEs were defined as those that resulted in temporary moderate to severe harm, required hospitalization, or resulted in permanent moderate to severe harm. We classified potential contributing factors according to (1) who was involved (person), (2) what were they doing (tasks), (3) what tools/technologies were they using (tools/technologies), (4) where did the event take place (environment), (5) what organizational conditions contributed to the event? (organization), (6) patient (including parents), and (7) professional-professional collaboration. A blinded panel of dental experts conducted a second review to confirm the presence of an AE. RESULTS: Fifty-nine cases had 1 or more harmful AEs. Pain occurred most frequently (27.1%), followed by nerve injury (16.9%), hard tissue injury (15.2%), and soft tissue injury (15.2%). Forty percent of the cases were classified as "temporary not moderate to severe harm." Person (training, supervision, and fatigue) was the most common contributing factor (31.5%), followed by patient (noncompliance, unsafe practices at home, low health literacy, 17.1%), and professional-professional collaboration (15.3%). CONCLUSIONS: Pain was the most common harmful AE identified. Person, patient, and professional-professional collaboration were the most frequently assessed factors associated with harmful AEs.

Identifying and Decreasing Sharps Injuries Through Root Cause Analysis in a Large Urban Hospital System.

BACKGROUND: Despite safety mandates and interventions, sharps injuries remain an occupational risk for registered nurses (RNs). Sharps and needlestick injuries increase the risk of exposure to blood-borne pathogens. Post-exposure direct and indirect costs of these percutaneous injuries have been estimated at about US$700 per incident. The goal of this quality improvement project was to identify root causes of sharps injuries for RNs at a large urban hospital system. METHODS: A retrospective evaluation of sharps injuries sustained by RNs, identification epsication of themes or root causes, and the development of a fishbone diagram to sort the causes into categories to identify workable solutions were conducted. Fisher's exact tests were performed to identify association between variables and root causes. FINDINGS: A total of 47 sharps injuries were reported from January 2020 through June 2020. Among sharps injuries sustained by nurses, 68.1% were among nurses 19 to 25 years of age and 57.4% reported job tenure of 1 to 2 years. There was a statistically significant association between root causes and tenure range, gender, and procedure type (p < .05) with moderate effect size (Cramer's V = 0.35-0.60). Technique also was a primary cause of sharps injuries for blood draw (77%), discontinuing line (75%), injection (46%), intravenous (IV) start (100%), and suturing (50%). CONCLUSIONS/APPLICATIONS TO PRACTICE: Technique and patient behavior were primary root causes of sharps injuries in this study. More sharps injuries caused by technique occurred among nurses with job tenure of 1 to 10 years, female, blood draw, discontinuing line, injection, IV start, and suturing procedures. The root cause analysis identified tenure, technique, and behavior as potential root causes of sharps injuries specifically occurring most during blood draw and injections at a large urban hospital system. These findings will inform nurses, especially new nurses in the proper use of safety devices and behaviors to prevent injury.

Application of the International System for Reporting Serous Fluid Cytopathology to pericardial fluid: Root cause analysis of indeterminate diagnoses, cytohistological correlation, and assessment of malignancy risk.

BACKGROUND: This study investigates the utility of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) in the categorization of pericardial fluid and assesses the diagnostic performance and risk of malignancy (ROM) for each of the diagnostic categories. METHODS: All pericardial fluid cases at the Yale School of Medicine between January 1, 2017, and December 31, 2020, were reviewed. The diagnoses were reclassified into five categories according to the ISRSFC: nondiagnostic (ND), negative for malignancy (NFM), atypia of uncertain significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). ROM and performance parameters of each category were calculated. RESULTS: After reclassification, the distribution of 465 pericardial fluid cases in each category was as follows: ND, 19 (4.1%); NFM, 332 (71.4%); AUS, 21 (4.5%); SFM, 11 (2.4%); and MAL, 82 (17.6%). Confirmatory follow-ups were available for 16 ND (66.7%), 299 NFM (90%), 15 AUS (71%), 5 SFM (45.5%), and 30 MAL cases (36.6%). The ROM was 0% for ND, 1.3% for NFM (4 of 332), 20% for AUS (3 of 15), and 100% for both SFM (5 of 5) and MAL (27 of 27). The diagnostic performance was as follows: sensitivity, 87% (27 of 31); specificity, 100% (292 of 292); positive predictive value (PPV), 100% (27 of 27); negative predictive value (NPV), 98.6% (292 of 296); and diagnostic accuracy, 98.8% (319 of 323). CONCLUSIONS: The ISRSFC is a highly useful system for the reporting of pericardial fluid and risk assessment, given that it offers high sensitivity, specificity, PPV, NPV, and diagnostic accuracy. The application of this system may help to better categorize pericardial fluid and facilitate the standardization of cytopathology reporting.

Competency-Based Medical Education in a Norm-Referenced World: A Root Cause Analysis of Challenges to the Competency-Based Paradigm in Medical School.

Competency-based medical education (CBME) requires a criterion-referenced approach to assessment. However, despite best efforts to advance CBME, there remains an implicit, and at times, explicit, demand for norm-referencing, particularly at the junction of undergraduate medical education (UME) and graduate medical education (GME). In this manuscript, the authors perform a root cause analysis to determine the underlying reasons for continued norm-referencing in the context of the movement toward CBME. The root cause analysis consisted of 2 processes: (1) identification of potential causes and effects organized into a fishbone diagram and (2) identification of the 5 whys. The fishbone diagram identified 2 primary drivers: the false notion that measures such as grades are truly objective and the importance of different incentives for different key constituents. From these drivers, the importance of norm-referencing for residency selection was identified as a critical component. Exploration of the 5 whys further detailed the reasons for continuation of norm-referenced grading to facilitate selection, including the need for efficient screening in residency selection, dependence upon rank-order lists, perception that there is a best outcome to the match, lack of trust between residency programs and medical schools, and inadequate resources to support progression of trainees. Based on these findings, the authors argue that the implied purpose of assessment in UME is primarily stratification for residency selection. Because stratification requires comparison, a norm-referenced approach is needed. To advance CBME, the authors recommend reconsideration of the approach to assessment in UME to maintain the purpose of selection while also advancing the purpose of rendering a competency decision. Changing the approach will require a collaboration between national organizations, accrediting bodies, GME programs, UME programs, students, and patients/societies. Details are provided regarding the specific approaches required of each key constituent group.

Validity of root cause analysis in investigating adverse events in psychiatry.

Root cause analysis (RCA), imported from high-reliability industries into health two decades ago, is the mandated methodology to investigate adverse events in most health systems. In this analysis, we argue that the validity of RCA in health and in psychiatry must be established, given the impact of these investigations on mental health policy and practice.

A root cause analysis to identify the mechanistic drivers of immunogenicity against the anti-VEGF biotherapeutic brolucizumab.

Immunogenicity against intravitreally administered brolucizumab has been previously described and associated with cases of severe intraocular inflammation, including retinal vasculitis/retinal vascular occlusion (RV/RO). The presence of antidrug antibodies (ADAs) in these patients led to the initial hypothesis that immune complexes could be key mediators. Although the formation of ADAs and immune complexes may be a prerequisite, other factors likely contribute to some patients having RV/RO, whereas the vast majority do not. To identify and characterize the mechanistic drivers underlying the immunogenicity of brolucizumab and the consequence of subsequent ADA-induced immune complex formation, a translational approach was performed to bridge physicochemical characterization, structural modeling, sequence analysis, immunological assays, and a quantitative systems pharmacology model that mimics physiological conditions within the eye. This approach revealed that multiple factors contributed to the increased immunogenic potential of brolucizumab, including a linear epitope shared with bacteria, non-natural surfaces due to the single-chain variable fragment format, and non-native drug species that may form over prolonged time in the eye. Consideration of intraocular drug pharmacology and disease state in a quantitative systems pharmacology model suggested that immune complexes could form at immunologically relevant concentrations modulated by dose intensity. Assays using circulating immune cells from treated patients or treatment-naïve healthy volunteers revealed the capacity of immune complexes to trigger cellular responses such as enhanced antigen presentation, platelet aggregation, endothelial cell activation, and cytokine release. Together, these studies informed a mechanistic understanding of the clinically observed immunogenicity of brolucizumab and associated cases of RV/RO.

Priorities and root cause analysis of quality and safety problems in chilean hospitals / Prioridades y análisis de las causas de los problemas de calidad y seguridad en hospitales chilenos

BACKGROUND: Quality improvement is an important component of hospital operations. AIM: To prioritise clinical quality and safety problems in Chilean hospitals according to their severity, frequency, and detectability. MATERIAL AND METHODS: The study was conducted between December 2018 and June 2019. To identify quality and safety problems, an exploratory study was conducted using an online survey aimed to those responsible for clinical quality and safety in Chilean hospitals. The survey was sent to 94 hospitals and completed by quality management personnel at 34 hospitals, yielding a total of 25 valid surveys for analysis. Based on the information gathered, a risk priority score was computed to rank the problems surveyed. Focus groups were held to find the root causes of the quality and safety problem with the highest risk priority score. RESULTS: The three highest risk priorities were:1 ineffective interprofessional communication,2 lack of leadership for addressing frequently recurring safety issues, and3 antimicrobial resistance due to inappropriate use of antibiotics. For the communication problem, the focus group found two main root causes: those due to personnel and those relating to the hospitals themselves. CONCLUSIONS: Hospitals can systematically use the proposed approach to categorize their main clinical quality and safety problems, analyze their causes, and then design solutions.

ANTECEDENTES: La mejora continua de la calidad es un componente importante en las actividades hospitalarias. OBJETIVO: Priorizar los problemas de calidad y seguridad en hospitales chilenos de acuerdo a su severidad, frecuencia y detectabilidad. MATERIAL Y MÉTODOS: Se efectuó un estudio exploratorio con una encuesta en línea para detectar problemas de calidad y seguridad, dirigida a quienes están a cargo de los problemas de calidad y seguridad en los hospitales. La encuesta fue enviada a 94 hospitales y respondida por los encargados de calidad y seguridad en 34 de ellos, lográndose 25 encuestas válidas para análisis. El estudio se llevó a cabo entre diciembre de 2018 y junio de 2019. Se diseñó una escala de prioridades de riesgo para determinar la importancia relativa de los problemas detectados. Se llevaron a cabo grupos focales para determinar las causas del problema más importante. RESULTADOS: En Chile, los problemas de calidad y seguridad más importantes son la falta de comunicación interprofesional, falta de liderazgo para abordar los problemas de seguridad y calidad, y resistencia a antibióticos debido a su uso inapropiado. Problemas relacionados al personal y relacionados al hospital fueron las causas primarias de la falta de comunicación. CONCLUSIONES: Los hospitales podrían utilizar este enfoque de forma sistemática para categorizar sus principales problemas de calidad y seguridad, analizar las causas y diseñar soluciones.