Kaiser Permanente South Sacramento Medical Center

PURPOSE BRAF V600E mutations are rarely associated with objective responses to the BRAF inhibitor vemurafenib in patients with metastatic colorectal cancer (CRC). Blockade of BRAF V600E by vemurafenib causes feedback upregulation of EGFR, whose signaling activities can be impeded by cetuximab. METHODS One hundred six patients with BRAF V600E -mutated metastatic CRC previously treated with one or two regimens were randomly assigned to irinotecan and cetuximab with or without vemurafenib (960 mg PO twice daily). RESULTS Progression-free survival, the primary end point, was improved with the addition of vemurafenib (hazard ratio, 0.50, P = .001). The response rate was 17% versus 4% ( P = .05), with a disease control rate of 65% versus 21% ( P < .001). A decline in circulating tumor DNA BRAF V600E variant allele frequency was seen in 87% versus 0% of patients ( P < .001), with a low incidence of acquired RAS alterations at the time of progression. RNA profiling suggested that treatment benefit did not depend on previously established BRAF subgroups or the consensus molecular subtype. CONCLUSION Simultaneous inhibition of EGFR and BRAF combined with irinotecan is effective in BRAF V600E -mutated CRC.

BACKGROUND: Sporadic vascular malformations (VMs) are complex congenital anomalies of blood vessels that lead to stroke, life-threatening bleeds, disfigurement, overgrowth, and/or pain. Therapeutic options are severely limited, and multidisciplinary management remains challenging, particularly for high-flow arteriovenous malformations (AVM). METHODS: To investigate the pathogenesis of sporadic intracranial and extracranial VMs in 160 children in which known genetic causes had been excluded, we sequenced DNA from affected tissue and optimized analysis for detection of low mutant allele frequency. RESULTS: We discovered multiple mosaic-activating variants in 4 genes of the RAS/MAPK pathway, KRAS, NRAS, BRAF, and MAP2K1, a pathway commonly activated in cancer and responsible for the germline RAS-opathies. These variants were more frequent in high-flow than low-flow VMs. In vitro characterization and 2 transgenic zebrafish AVM models that recapitulated the human phenotype validated the pathogenesis of the mutant alleles. Importantly, treatment of AVM-BRAF mutant zebrafish with the BRAF inhibitor vemurafinib restored blood flow in AVM. CONCLUSION: Our findings uncover a major cause of sporadic VMs of different clinical types and thereby offer the potential of personalized medical treatment by repurposing existing licensed cancer therapies. FUNDING: This work was funded or supported by grants from the AVM Butterfly Charity, the Wellcome Trust (UK), the Medical Research Council (UK), the UK National Institute for Health Research, the L'Oreal-Melanoma Research Alliance, the European Research Council, and the National Human Genome Research Institute (US).

We conduct an empirical investigation of the impact of queue management on patients’ average wait time and length of stay (LOS). Using an emergency department’s (ED) patient-level data from 2007 to 2010, we find that patients’ average wait time and LOS are longer when physicians are assigned patients under a pooled queuing system with a fairness constraint compared to a dedicated queuing system with the same fairness constraint. Using a difference-in-differences approach, we find the dedicated queuing system is associated with a 17% decrease in average LOS and a 9% decrease in average wait time relative to the control group—a 39-minute reduction in LOS and a four-minute reduction in wait time for an average patient of medium severity in this ED. Interviews and observations of physicians suggest that the improved performance stems from the physicians’ increased ownership over patients and resources that is afforded by a dedicated queuing system, which enables physicians to more actively manage the flow of patients into and out of ED beds. Our findings suggest that the benefits from improved flow management in a dedicated queuing system can be large enough to overcome the longer wait time predicted to arise from nonpooled queues. We conduct additional analyses to rule out alternate explanations for the reduced average wait time and LOS in the dedicated system, such as stinting and decreased quality of care. Our paper has implications for healthcare organizations and others seeking to reduce patient wait time and LOS without increasing costs. This paper was accepted by Serguei Netessine, operations management.

OBJECTIVE: To identify the sensitivity of several readily available diagnostic tests for onychomycosis. DESIGN: Cross-sectional study. SETTING: Dermatology and podiatry departments at a teaching hospital. PATIENTS: Sixty-three adult men and women with a clinical examination highly suggestive of onychomycosis. MAIN OUTCOME MEASURES: Sensitivity of each test and of several test combinations. RESULTS: Nail samples underwent 6 diagnostic tests. Routine histopathologic examination with periodic acid-Schiff stain (PAS) (PATHPAS) was 85% sensitive. Sensitivities for potassium hydroxide dissolution and centrifugation combined with PAS, fluorescent brightener, or chlorazol black E were 57%, 53%, and 53%, respectively. Culture on Sabouraud agar withchloramphenicol and cycloheximide (Mycosel agar) was 32% sensitive; on Littman-oxgall agar, 23% sensitive. The most sensitive combination of tests, both culture methods plus PATHPAS, was 94% sensitive (not statistically different from the sensitivity of PATHPAS alone [P = .26]). CONCLUSIONS: When onychomycosis is suspected clinically, PATHPAS of the nail is the single most sensitive of the diagnostic tests we evaluated. Because it is quickly performed and relatively operator independent, PATHPAS is practical for clinical and research purposes. Further study is needed to determine if sensitivity may be enhanced by combining PATHPAS with cultures obtained by several collection methods (clipping, curettage, and shaving). Such combinations may serve as sensitive and efficient strategies for diagnosing onychomycosis.

PURPOSE: Nonventilator hospital-acquired pneumonia (NV-HAP) is an underreported and unstudied disease, with potential for measurable outcomes, fiscal savings, and improvement in quality of life. The purpose of our study was to (a) identify the incidence of NV-HAP in a convenience sample of U.S. hospitals and (b) determine the effectiveness of reliably delivered basic oral nursing care in reducing NV-HAP. DESIGN: A descriptive, quasi-experimental study using retrospective comparative outcomes to determine (a) the incidence of NV-HAP and (b) the effectiveness of enhanced basic oral nursing care versus usual care to prevent NV-HAP after introduction of a basic oral nursing care initiative. METHODS: We used the International Statistical Classification of Diseases and Related Problems (ICD-9) codes for pneumonia not present on admission and verified NV-HAP diagnosis using the U.S. Centers for Disease Control and Prevention diagnostic criteria. We completed an evidence-based gap analysis and designed a site-specific oral care initiative designed to reduce NV-HAP. The intervention process was guided by the Influencer Model (see Figure) and participatory action research. FINDINGS: We found a substantial amount of unreported NV-HAP. After we initiated our oral care protocols, the rate of NV-HAP per 100 patient days decreased from 0.49 to 0.3 (38.8%). The overall number of cases of NV-HAP was reduced by 37% during the 12-month intervention period. The avoidance of NV-HAP cases resulted in an estimated 8 lives saved, $1.72 million cost avoided, and 500 extra hospital days averted. The extra cost for therapeutic oral care equipment was $117,600 during the 12-month intervention period. Cost savings resulting from avoided NV-HAP was $1.72 million. Return on investment for the organization was $1.6 million in avoided costs. CONCLUSIONS: NV-HAP should be elevated to the same level of concern, attention, and effort as prevention of ventilator-associated pneumonia in hospitals. CLINICAL RELEVANCE: Nursing needs to lead the way in the design and implementation of policies that allow for adequate time, proper oral care supplies, ease of access to supplies, clear procedures, and outcome monitoring ensuring that patients are protected from NV-HAP.

Background: Many low-risk patients with acute pulmonary embolism (PE) in the emergency department (ED) are eligible for outpatient care but are hospitalized nonetheless. One impediment to home discharge is the difficulty of identifying which patients can safely forgo hospitalization. Objective: To evaluate the effect of an integrated electronic clinical decision support system (CDSS) to facilitate risk stratification and decision making at the site of care for patients with acute PE. Design: Controlled pragmatic trial. (ClinicalTrials.gov: NCT03601676). Setting: All 21 community EDs of an integrated health care delivery system (Kaiser Permanente Northern California). Patients: Adult ED patients with acute PE. Intervention: Ten intervention sites selected by convenience received a multidimensional technology and education intervention at month 9 of a 16-month study period (January 2014 to April 2015); the remaining 11 sites served as concurrent controls. Measurements: The primary outcome was discharge to home from either the ED or a short-term (<24-hour) outpatient observation unit based in the ED. Adverse outcomes included return visits for PE-related symptoms within 5 days and recurrent venous thromboembolism, major hemorrhage, and all-cause mortality within 30 days. A difference-in-differences approach was used to compare pre-post changes at intervention versus control sites, with adjustment for demographic and clinical characteristics. Results: Among 881 eligible patients diagnosed with PE at intervention sites and 822 at control sites, adjusted home discharge increased at intervention sites (17.4% pre- to 28.0% postintervention) without a concurrent increase at control sites (15.1% pre- and 14.5% postintervention). The difference-in-differences comparison was 11.3 percentage points (95% CI, 3.0 to 19.5 percentage points; P = 0.007). No increases were seen in 5-day return visits related to PE or in 30-day major adverse outcomes associated with CDSS implementation. Limitation: Lack of random allocation. Conclusion: Implementation and structured promotion of a CDSS to aid physicians in site-of-care decision making for ED patients with acute PE safely increased outpatient management. Primary Funding Source: Garfield Memorial National Research Fund and The Permanente Medical Group Delivery Science and Physician Researcher Programs.

N-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated. We identified three different novel and one known missense mutation in NAA10, de novo in 11 females, and due to maternal germ line mosaicism in another girl and her more severely affected and deceased brother. In vitro enzymatic assays for the novel, recurrent mutations p.(Arg83Cys) and p.(Phe128Leu) revealed reduced catalytic activity. X-inactivation was random in five females. The core phenotype of X-linked NAA10-related N-terminal-acetyltransferase deficiency in both males and females includes developmental delay, severe intellectual disability, postnatal growth failure with severe microcephaly, and skeletal or cardiac anomalies. Genotype-phenotype correlations within and between both genders are complex and may include various factors such as location and nature of mutations, enzymatic stability and activity, and X-inactivation in females.

OBJECTIVES: We determined whether implementing the Pediatric Emergency Care Applied Research Network (PECARN) traumatic brain injury (TBI) prediction rules and providing risks of clinically important TBIs (ciTBIs) with computerized clinical decision support (CDS) reduces computed tomography (CT) use for children with minor head trauma. METHODS: Nonrandomized trial with concurrent controls at 5 pediatric emergency departments (PEDs) and 8 general EDs (GEDs) between November 2011 and June 2014. Patients were <18 years old with minor blunt head trauma. Intervention sites received CDS with CT recommendations and risks of ciTBI, both for patients at very low risk of ciTBI (no Pediatric Emergency Care Applied Research Network rule factors) and those not at very low risk. The primary outcome was the rate of CT, analyzed by site, controlling for time trend. RESULTS: < .05) but modestly (2.3%-3.7%) at 2 of 4 intervention PEDs for children at very low risk. The other 2 PEDs had small (0.8%-1.5%) nonsignificant decreases. CT rates did not decrease consistently at the intervention GEDs, with low baseline CT rates (2.1%-4.0%) in those at very low risk. The control PED had little change in CT use in similar children (from 1.6% to 2.9%); the control GED showed a decrease in the CT rate (from 7.1% to 2.6%). For all children with minor head trauma, intervention sites had small decreases in CT rates (1.7%-6.2%). CONCLUSIONS: The implementation of TBI prediction rules and provision of risks of ciTBIs by using CDS was associated with modest, safe, but variable decreases in CT use. However, some secular trends were also noted.

BACKGROUND: High-fidelity patient simulation has been praised for its ability to recreate lifelike training conditions. The degree to which high fidelity simulation elicits acute emotional and physiologic stress among participants - and the influence of acute stress on clinical performance in the simulation setting - remain areas of active exploration. We examined the relationship between residents' self-reported anxiety and a proxy of physiologic stress (heart rate) as well as their clinical performance in a simulation exam using a validated assessment of non-technical skills, the Ottawa Crisis Resource Management Global Rating Scale (Ottawa GRS). METHODS: This was a prospective observational cohort study of emergency medicine residents at a single academic center. Participants managed a simulated clinical encounter. Anxiety was assessed using a pre- and post-simulation survey, and continuous cardiac monitoring was performed on each participant during the scenario. Performance in the simulation scenario was graded by faculty raters using a critical actions checklist and the Ottawa GRS instrument. RESULTS: Data collection occurred during the 2011 academic year. Of 40 eligible residents, 34 were included in the analysis. The median baseline heart rate for participants was 70 beats per minute (IQR: 62 - 78). During the simulation, the median maximum heart rate was 140 beats per minute (IQR: 137 - 151). The median minimum heart rate during simulation was 81 beats per minute (IQR: 72 - 92), and mean heart rate was 117 beats per minute (95% CI: 111 - 123). Pre- and post-simulation anxiety scores were equal (mean 3.3, IQR: 3 to 4). The minimum and maximum Overall Ottawa GRS scores were 2.33 and 6.67, respectively. The median Overall score was 5.63 (IQR: 5.0 to 6.0). Of the candidate predictors of Overall performance in a multivariate logistic regression model, only PGY status showed statistical significance (P = 0.02). CONCLUSIONS: Simulation is associated with physiologic stress, and heart rate elevation alone correlates poorly with both perceived stress and performance. Non-technical performance in the simulation setting may be more closely tied to one's level of clinical experience than to perceived or actual stress.

OBJECTIVE: Breast pumping or hand expression may be recommended when newborns latch or suck poorly. A recent trial found worse outcomes among mothers who used a breast pump in the early postpartum period. The objective of this study was to compare bilateral electric breast pumping to hand expression among mothers of healthy term infants feeding poorly at 12-36 h after birth. DESIGN: Randomised controlled trial. SETTING: Well-baby nursery and postpartum unit. PATIENTS: 68 mothers of newborns 12-36 h old who were latching or sucking poorly were randomly assigned to either 15 min of bilateral electric pumping or 15 min of hand expression. MAIN OUTCOME MEASURES: Milk transfer, maternal pain, breastfeeding confidence and breast milk expression experience (BMEE) immediately after the intervention, and breastfeeding rates at 2 months after birth. RESULTS: The median volume of expressed milk (range) was 0.5 (0-5) ml for hand expressing mothers and 1 (0-40) ml for pumping mothers (p=0.07). Maternal pain, breastfeeding confidence and BMEE did not differ by intervention. At 2 months, mothers assigned to hand expression were more likely to be breastfeeding (96.1%) than mothers assigned to breast pumping (72.7%) (p=0.02). CONCLUSIONS: Hand expression in the early postpartum period appears to improve eventual breastfeeding rates at 2 months after birth compared with breast pumping, but further research is needed to confirm this. However, in circumstances where either pumping or hand expression would be appropriate for healthy term infants 12-36 h old feeding poorly, providers should consider recommending hand expression.

There are limited data on the longitudinal frequency and severity of the symptoms and complications of achondroplasia. We undertook a retrospective electronic chart review of 114 patients to develop a more thorough understanding of the lifetime impact of achondroplasia. Craniocervical stenosis (involving the foramen magnum with or without cervical vertebrae C1 and/or C2) was noted in nearly 50% of patients with craniovertebral junction imaging; however, corrective decompression surgery was only needed in 6% of patients. No children in our cohort died at 4 years of age or under. Kyphosis was present in most patients but usually resolved in early childhood. Cervical and lumbar stenosis were diagnosed in children and adults while, genu varum, elbow contractures, and radial head dislocations were identified during childhood. Central sleep apnea and obstructive sleep apnea were present in children, while the diagnosis of obstructive sleep apnea was shown to recur in adulthood. Cardiovascular risk factors were present in only 7% of patients. A range of mental health disorders were identified, with most diagnoses being made before 18 years of age. Our data show that achondroplasia has a significant impact on patients' physical health, and complications continue to be reported and require intervention throughout patients' lifetimes. This highlights the need for continuous support beyond pediatric care, by adult care clinicians experienced with managing the long-term complications of achondroplasia.

The association of Crohn's disease (CD) and Sweet's syndrome is rare and the presence of Sjögren's syndrome in Crohn's disease is even rarer, with only three reports found in the literature. We describe two cases of Crohn's disease associated with Sweet's syndrome, one of which is the first case of CD and Sweet's concomitantly associated with Sjogren's syndrome. Both cases responded rapidly to Infliximab therapy with complete resolution of the skin lesions.

OBJECTIVES: Appropriate use of cranial computed tomography (CT) scanning in patients with mild blunt head trauma and preinjury anticoagulant or antiplatelet use is unknown. The objectives of this study were: 1) to identify risk factors for immediate traumatic intracranial hemorrhage (tICH) in patients with mild head trauma and preinjury warfarin or clopidogrel use and 2) to derive a clinical prediction rule to identify patients at low risk for immediate tICH. METHODS: This was a prospective, observational study at two trauma centers and four community hospitals that enrolled adult emergency department (ED) patients with mild blunt head trauma (initial ED Glasgow Coma Scale [GCS] score 13 to 15) and preinjury warfarin or clopidogrel use. The primary outcome measure was immediate tICH, defined as the presence of ICH or contusion on the initial cranial CT. Risk for immediate tICH was analyzed in 11 independent predictor variables. Clinical prediction rules were derived with both binary recursive partitioning and multivariable logistic regression. RESULTS: A total of 982 patients with a mean (± standard deviation [SD]) age of 75.4 (±12.6) years were included in the analysis. Sixty patients (6.1%; 95% confidence interval [CI] = 4.7% to 7.8%) had immediate tICH. History of vomiting (relative risk [RR] = 3.53; 95% CI = 1.80 to 6.94), abnormal mental status (RR = 2.85; 95% CI = 1.65 to 4.92), clopidogrel use (RR = 2.52; 95% CI = 1.55 to 4.10), and headache (RR = 1.81; 95% CI = 1.11 to 2.96) were associated with an increased risk for immediate tICH. Both binary recursive partitioning and multivariable logistic regression were unable to derive a clinical prediction model that identified a subset of patients at low risk for immediate tICH. CONCLUSIONS: While several risk factors for immediate tICH were identified, the authors were unable to identify a subset of patients with mild head trauma and preinjury warfarin or clopidogrel use who are at low risk for immediate tICH. Thus, the recommendation is for urgent and liberal cranial CT imaging in this patient population, even in the absence of clinical findings.

Field triage guidelines recommend transport of head-injured patients on anticoagulants or antiplatelets to a higher-level trauma center based on studies suggesting a high incidence of traumatic intracranial hemorrhage (tICH). We compared the incidence of tICH in older adults transported by emergency medical services (EMS) with and without anticoagulation or antiplatelet use and evaluated the accuracies of different sets of field triage criteria to identify tICH. This was a prospective, observational study at five EMS agencies and 11 hospitals. Older adults (≥55 years) with head trauma and transported by EMS from August 2015 to September 2016 were eligible. EMS providers completed standardized data forms and patients were followed through emergency department (ED) or hospital discharge. We enrolled 1304 patients; 1147 (88%) received a cranial computed tomography (CT) scan and were eligible for analysis. Four hundred thirty-four (33%) patients had anticoagulant or antiplatelet use and 112 (10%) had tICH. The incidence of tICH in patients with (11%, 95% confidence interval [CI] 8%-14%) and without (9%, 95% CI 7%-11%) anticoagulant or antiplatelet use was similar. Anticoagulant or antiplatelet use was not predictive of tICH on adjusted analysis. Steps 1-3 criteria alone were not sensitive in identifying tICH (27%), whereas the addition of anticoagulant or antiplatelet criterion improved sensitivity (63%). Other derived sets of triage criteria were highly sensitive (>98%) but poorly specific (<11%). The incidence of tICH was similar between patients with and without anticoagulant or antiplatelet use. Use of anticoagulant or antiplatelet medications was not a risk factor for tICH. We were unable to identify a set of triage criteria that was accurate for trauma center need.

We report 13 new individuals with duplications in Xp11.22-p11.23. The index family has one male and two female members in three generations with mild-severe intellectual disability (ID), speech delay, dysmorphic features, early puberty, constipation, and/or hand and foot abnormalities. Affected individuals were found to have two small duplications in Xp11.22 at nucleotide position (hg19) 50,112,063-50,456,458 bp (distal) and 53,160,114-53,713,154 bp (proximal). Collectively, these two regions include 14 RefSeq genes, prompting collection of a larger cohort of patients, in an attempt to delineate critical genes associated with the observed phenotype. In total, we have collected data on nine individuals with duplications overlapping the distal duplication region containing SHROOM4 and DGKK and eight individuals overlapping the proximal region including HUWE1. Duplications of HUWE1 have been previously associated with non-syndromic ID. Our data, with previously published reports, suggest that duplications involving SHROOM4 and DGKK may represent a new syndromic X-linked ID critical region associated with mild to severe ID, speech delay +/- dysarthria, attention deficit disorder, precocious puberty, constipation, and motor delay. We frequently observed foot abnormalities, 5th finger clinodactyly, tapering fingers, constipation, and exercise intolerance in patients with duplications of these two genes. Regarding duplications including the proximal region, our observations agree with previous studies, which have found associations with intellectual disability. In addition, expressive language delay, failure to thrive, motor delay, and 5th finger clinodactyly were also frequently observed in patients with the proximal duplication.

Abstract Cardiac arrest has many implications for morbidity and mortality. Few interventions have been shown to improve return of spontaneous circulation (ROSC) and long‐term outcomes after cardiac arrest. Ischemic‐reperfusion injury upon achieving ROSC creates an imbalance between oxygen supply and demand. Multiple events occur in the postcardiac arrest period, including excitotoxicity, mitochondrial dysfunction, and oxidative stress and inflammation, all of which contribute to ongoing brain injury and cellular death. Given that complex pathophysiology underlies global brain hypoxic ischemia, neuroprotective strategies targeting multiple stages of the neuropathologic cascade should be considered as a means of mitigating secondary neuronal injury and improving neurologic outcomes and survival in cardiac arrest victims. In this review article, we discuss a number of different pharmacologic agents that may have a potential role in targeting these injurious pathways following cardiac arrest. Pharmacologic therapies most relevant for discussion currently include memantine, perampanel, magnesium, propofol, thiamine, methylene blue, vitamin C, vitamin E, coenzyme Q 10 , minocycline, steroids, and aspirin.

BACKGROUND: Capsule endoscopy (CE) is a new technology that has been shown to have superior diagnostic yield compared with other methods of evaluating the small bowel. However, there have not been many studies supporting capsule endoscopy's impact on clinical outcomes. This study is a chart review evaluating the diagnostic yield and the impact of CE on management and clinical outcomes. METHODS: Retrospective chart review was performed on 145 patients who had undergone capsule endoscopy. Demographic characteristics, indication, prior diagnostic tests, capsule findings, interventions, and clinical outcomes up to 8 months following CE were evaluated. Indications included five main categories that were overt gastrointestinal (GI) bleed, occult GI bleed, abdominal pain, Crohn's disease, and iron deficiency anemia. Findings on capsule endoscopy were classified into angiodysplasias, ulcers, gastritis and/or duodenitis, ulcers suggestive of Crohn's and normal findings. Interventions performed based on capsule findings were recorded, which included the discontinuation of nonsteroidal anti-inflammatory drugs (NSAIDS), further diagnostic or therapeutic studies, increase in medications, and surgery. Positive outcomes including stabilization or improvement of hemoglobin, decreased need for transfusions, improved symptoms of pain, and a decrease in medications based on interventions were assessed. RESULTS: There were 145 patients who underwent CE. The indications for CE were overt GI bleed (38%), occult GI bleed (22%), abdominal pain (20%), Crohn's (12%), iron deficiency anemia (2.7%), and miscellaneous (4%). Eighty percent achieved completion and 6 patients had complications of capsule retention with 4 requiring surgery. The overall diagnostic yield was 69% and included findings of angiodysplasias (24%), intestinal ulcers (13%) gastritis or duodenitis (13.8%), ulcers suggestive of Crohn's disease (8.9%), and mass or polyp (3.4%). Based on capsule findings, 35.8% of patients had an intervention. Of the patients who received intervention, 71.7% had a positive clinical outcome (P= 0.032). CONCLUSIONS: The high diagnostic yield of CE influences clinical management leading to improved outcomes. However, the utility of CE may be greater in patients who are referred for certain indications or have specific findings. Additional studies are needed to clarify the role of capsule endoscopy in the evaluation of various indications as well as identify factors associated with positive outcomes.

OBJECTIVE: Emergency department (ED) crowding creates issues with patient satisfaction, long wait times and leaving the ED without being seen by a doctor (LWBS). Our objective was to evaluate how applying Lean principles to develop a Rapid Triage and Treatment (RTT) system affected ED metrics in our community hospital. METHODS: Using Lean principles, we made ED process improvements that led to the RTT system. Using this system, patients undergo a rapid triage with low-acuity patients seen and treated by a physician in the triage area. No changes in staffing, physical space or hospital resources occurred during the study period. We then performed a retrospective, observational study comparing hospital electronic medical record data six months before and six months after implementation of the RTT system. RESULTS: ED census was 30,981 in the six months prior to RTT and 33,926 after. Ambulance arrivals, ED patient acuity and hospital admission rates were unchanged throughout the study periods. Mean ED length of stay was longer in the period before RTT (4.2 hours, 95% confidence interval [CI] = 4.2-4.3; standard deviation [SD] = 3.9) than after (3.6 hours, 95% CI = 3.6-3.7; SD = 3.7). Mean ED arrival to physician start time was 62.2 minutes (95% CI = 61.5-63.0; SD = 58.9) prior to RTT and 41.9 minutes (95% CI = 41.5-42.4; SD = 30.9) after. The LWBS rate for the six months prior to RTT was 4.5% (95% CI = 3.1-5.5) and 1.5% (95% CI = 0.6-1.8) after RTT initiation. CONCLUSION: Our experience shows that changes in ED processes using Lean thinking and available resources can improve efficiency. In this community hospital ED, use of an RTT system decreased patient wait times and LWBS rates.

Importance: The risk of adverse events from ascending thoracic aorta aneurysm (TAA) is poorly understood but drives clinical decision-making. Objective: To evaluate the association of TAA size with outcomes in nonsyndromic patients in a large non-referral-based health care delivery system. Design, Setting, and Participants: The Kaiser Permanente Thoracic Aortic Aneurysm (KP-TAA) cohort study was a retrospective cohort study at Kaiser Permanente Northern California, a fully integrated health care delivery system insuring and providing care for more than 4.5 million persons. Nonsyndromic patients from a regional TAA safety net tracking system were included. Imaging data including maximum TAA size were merged with electronic health record (EHR) and comprehensive death data to obtain demographic characteristics, comorbidities, medications, laboratory values, vital signs, and subsequent outcomes. Unadjusted rates were calculated and the association of TAA size with outcomes was evaluated in multivariable competing risk models that categorized TAA size as a baseline and time-updated variable and accounted for potential confounders. Data were analyzed from January 2018 to August 2021. Exposures: TAA size. Main Outcomes and Measures: Aortic dissection (AD), all-cause death, and elective aortic surgery. Results: Of 6372 patients with TAA identified between 2000 and 2016 (mean [SD] age, 68.6 [13.0] years; 2050 female individuals [32.2%] and 4322 male individuals [67.8%]), mean (SD) initial TAA size was 4.4 (0.5) cm (828 individuals [13.0% of cohort] had initial TAA size 5.0 cm or larger and 280 [4.4%] 5.5 cm or larger). Rates of AD were low across a mean (SD) 3.7 (2.5) years of follow-up (44 individuals [0.7% of cohort]; incidence 0.22 events per 100 person-years). Larger initial aortic size was associated with higher risk of AD and all-cause death in multivariable models, with an inflection point in risk at 6.0 cm. Estimated adjusted risks of AD within 5 years were 0.3% (95% CI, 0.3-0.7), 0.6% (95% CI, 0.4-1.3), 1.5% (95% CI, 1.2-3.9), 3.6% (95% CI, 1.8-12.8), and 10.5% (95% CI, 2.7-44.3) in patients with TAA size of 4.0 to 4.4 cm, 4.5 to 4.9 cm, 5.0 to 5.4 cm, 5.5 to 5.9 cm, and 6.0 cm or larger, respectively, in time-updated models. Rates of the composite outcome of AD and all-cause death were higher than for AD alone, but a similar inflection point for increased risk was observed at 6.0 cm. Conclusions and Relevance: In a large sociodemographically diverse cohort of patients with TAA, absolute risk of aortic dissection was low but increased with larger aortic sizes after adjustment for potential confounders and competing risks. Our data support current consensus guidelines recommending prophylactic surgery in nonsyndromic individuals with TAA at a 5.5-cm threshold.

BACKGROUND: Lithium overdose primarily results in neurologic toxicity; however, cardiac effects have also been reported. Our aim was to describe a large cohort of hospitalized lithium overdose patients. Specifically we were interested in reported cardiac complications, frequency of hemodialysis (HD), and mortality. METHODS: This is a retrospective, observational case series of admitted isolated lithium exposure cases reported to the California Poison Control System (CPCS) from 2003 through 2007. Reported lithium exposure cases were identified by a search of our CPCS database. Only those cases resulting in hospital admission were included in this study. Cases with concomitant toxic exposures were excluded. Primary outcome variables were reported cardiac complications (defined as bradycardia with a heart rate < or =50 bpm, atrioventricular (AV) block, ventricular tachycardia, and ventricular fibrillation), administration of cardiovascular intervention (resuscitation, vasopressor medications, or cardiac pacing), and death. RESULTS: In the 5-year-study period 629 lithium cases were reported to the CPCS and 502 hospitalized cases were included in this study. There were 44 [8.8%; 95% confidence intervals (CI) 6.3, 11.2] cases of acute lithium exposure, 124 (24.7%; 95% CI 20.9, 28.5) cases of acute on chronic (AC) overdose, and 282 (56.2%; 95% CI 51.8, 60.5) cases of chronic overdose. Sixty-nine patients received hemodialysis. This includes 6 (13.6%) acute, 12 (9.7%) AC, and 45 (16.0%) chronic cases. There were four deaths (0.8%, 95% CI 0.2, 1.6). Cardiac complications were reported in 29 cases (5.7%, 95% CI 3.7, 7.7%) with 18 of these cases (18/29; 62%) being isolated bradycardias (without hypotension). Only seven patients with reported cardiac complication (7/29; 24.1%; 95% CI = 8.6, 39.7) required cardiovascular intervention and all of these were cases of chronic lithium toxicity. Two bradycardic arrests occurred in chronic lithium exposure cases, including one who died. CONCLUSION: In this cohort of hospitalized lithium exposure patients, death was rare. Reported cardiac complications were unusual with instances requiring cardiovascular intervention occurring only in cases of chronic lithium overdose. The majority of lithium toxicity cases were managed without HD.