Rhabdomyolysis and pancytopenia secondary to an unexpected interaction between ledipasvir/sofosbuvir, atorvastatin and colchicine

Case Presentation: A 65-year-old woman with hepatitis C-induced liver cirrhosis status-post liver transplantation, coronary artery disease and gout, presents with one week of progressive fatigue, weakness, and severe pain in her right leg and left shoulder. She was on atorvastatin for cardiac disease and had recently started Ledipasvir/Sofosbuvir for hepatitis C two months prior. She also reported sporadic colchicine use for gout and in the three weeks prior had been taking it daily. On exam, she had tenderness of her right thigh and left shoulder, but had no rashes, ecchymosis or bleeding. Joint examination was unremarkable. Labs were significant for creatine phosphokinase (CPK) 3146 IU/L (normal \u3c170), creatinine 1.25 mg/dl (\u3c1.16, at her baseline), urine myoglobulin of 19,700 ng/ml (\u3c45). Complete blood count revealed hemoglobin 8.3 g/dL, white blood cell count 1.6 K/uL and platelets 97 K/uL, which were all reduced from three weeks prior. The patient was diagnosed with rhabdomyolysis and pancytopenia, admitted to the hospital, and treated with aggressive intravenous fluids. Upon admission, atorvastatin and colchicine were discontinued, while Ledipasvir/Sofosbuvir were continued. The patient clinically improved and the CPK and pancytopenia resolved within one week and one month, respectively. Discussion: Rhabdomyolysis is a common condition requiring hospitalization. The focus of treatment is hydration and discontinuation of any offending agents. Patients taking Ledipasvir/Sofosbuvir are increasingly encountered in hospitals as this treatment for hepatitis C becomes more widespread. Ledipasvir/Sofosbuvir have been reported to cause asymptomatic elevations in CPK and concurrent usage with rosuvastatin can lead to increased risk of statin-related myopathy. This did not appear to translate to other statins, except for a single case suggesting atorvastatin to also be a culprit. Ledipasvir inhibits P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP), both of which are drug transporters. Inhibition of P-gp increases colchicine absorption, while inhibition of BCRP increases rosuvastatin, and theoretically atorvastatin absorption. Atorvastatin also acts as a P-gp inhibitor and colchicine has been shown to independently and in conjunction with statins, cause rhabdomyolysis and pancytopenia. Our case proposes that colchicine may have been the underlying trigger of rhabdomyolysis, suggested by the timing of drug initiation, concurrent pancytopenia and laboratory normalization following cessation of the offending medications. Conclusions: Patients on Ledipasvir/Sofosbuvir should be closely monitored while on combined atorvastatin and colchicine therapy due to the increased risk of rhabdomyolysis and pancytopenia, among other potential adverse effects of polypharmacy

Pathway for early sepsis identification and treatment in the skilled nursing facility

Background: Following hospitalization, a reported 20% of all Medicare patients are discharged to skilled nursing facilities (SNFs). Sepsis was the cause of 25-68% of readmissions from SNFs based on a review of Medicare readmissions from patients at 96 SNFs in southeast Michigan. Sepsis is also the most common all-cause admission diagnosis and represents over $20 billion in hospital-related costs. There is limited literature on processes for the identification and treatment of sepsis in the post-acute care setting, and nearly all interventions implemented in SNFs were designed for acute care. Appropriate treatment of sepsis in early stages for all patients, but importantly those at SNFs, is a clear opportunity to improve patient care and cost. Purpose: The purpose of the project is to develop a protocol for the early identification and treatment of sepsis that fits into the clinical resources available at SNFs to reduce hospital transfers. Description: The pathway was designed to include evidence-based interventions to fit within resources easily available at SNFs. A resource assessment was performed by interviewing SNF nurses to identify barriers to effective implementation, which included different staffing models, complex interventions, and limited access to critical care. A model was built on three main activities of screen, treat, and transfer (Figure 1). An initial assessment tool was based on easy to collect patient variables: temperature, white blood cell count, and mental status. Treatment and monitoring steps were based on recommendations from the Surviving Sepsis Campaign. Transfer criteria were clearly defined to include end-organ dysfunction or vital sign instability. The entire pathway is encapsulated into a two-page worksheet for easy use at the facility (Figure 2). Implementation at the SNFs was completed in a train-the-trainer style session. Initial education sessions at pilot sites were completed to develop presentation style, which included a variety of learning modalities, simulated cases, and workflow demonstrations. Throughout the training, key stakeholders were identified and their unique roles within the pathway were more clearly defined. Initial data collection at each SNF will include facility census, number of hospital transfers, and number of patients who received care through the pathway. Conclusions: To implement a complex protocol in a specialized clinical setting, SNFs, requires a deep understanding of the available resources and identification and engagement of key stakeholders: certified nursing aids, nurses, and post-acute care physicians

Code blue outcomes: Relation to the modified early warning score

Background: The Modified Early Warning Score (MEWS) is a physiological scoring system developed to identify patients in early stages of clinical deterioration and prevent delays in proper care. It consists of systolic blood pressure, heart rate, respiratory rate, temperature and level of consciousness. Higher MEWS are associated with greater mortality and need for intensive care. The relation of the MEWS to outcomes of in-hospital patient arrests, or codes, has not been extensively evaluated. If a clear relationship is established, it would provide a crucial tool in assisting doctors, patients, and families in goals of care discussions and clinical decisions. The intent of this study was to assess the relationship between the pre-code MEWS and the post-code outcome of patients on general inpatient units. Methods: This study sample included all adult general practice unit inpatients sustaining an arrest, classified as requiring CPR and/or intubation at a 802-bed tertiary care, urban, teaching hospital from July 2014 through June 2015. Data extracted included MEWS variables at 4 hours (hr) and 24hr before an event. Time windows of 2-6hr and 20-28hr were used for the 4hr and 24hr windows respectively. For missing points, the closest retrospective value was taken, even if outside the desired range. Level of consciousness (Alert, Verbal, Pain, Unresponsive) was inferred based on the nursing, therapy, nutritional notes or if the recorded pain score was \u3e0. The primary outcome was survival to hospital discharge. Univariate and multiple binary logistic regression models were used to assess the relationship between patient status at discharge and pre-code MEWS, adjusted for age, Charlson Comorbidity Index (CCI), and gender. Results: A total of 216 patients experienced arrests during the study period. At discharge, 53.1% of patients survived. Baseline demographics and MEWS are summarized in Table 1 for each outcome group. The odds ratio of death for the MEWS at 4hr was 0.89 (95% CI 0.75-1.07; p-value 0.24) (Figure 1). In a binary logistic regression model using 4hr MEWS, CCI, age, and gender, the outcome of death was not associated with the 4hr MEWS, but was with age (OR 0.98, 95% CI 0.96-1, p = 0.041). Conclusions: The MEWS has been associated with acute patient decompensation in the hospital, but in our study population, we did not find a relationship between the MEWS and patient survival at discharge following a code, even when adjusting for age and comorbidities. Events during the actual code event are known to affect survival, but were not evaluated in our study, which may contribute the negative result

The Applicability of New Orleans Criteria for Head Computed Tomography in Inpatient Falls With Injury

Background: Inpatient falls are a patient safety concern. Limited data exist on the utility of head computed tomography (CT) for inpatient falls. The New Orleans Criteria (NOC) is a validated tool to determine the appropriateness of neuroimaging in the emergency department for falls with minor head injury. This study aimed to evaluate whether the NOC could be applied to inpatient falls. Methods: This retrospective cohort study assessed 1 year of inpatient falls with injury at 5 inpatient facilities. Records were reviewed for demographic data, fall circumstances, laboratory results, components of the NOC, and head CT results. Cohorts included positive NOC (≥1 NOC finding) and negative NOC. Sensitivity and specificity were calculated for the NOC alone, NOC plus coagulopathy, and NOC or coagulopathy for acute intracranial process. Results: Of 332 inpatient falls with injury, 188 (57%) received a head CT. Of the 250 (75.3%) NOC-positive cases, 159 (63.6%) received a head CT. Of all patients who received a head CT, 7 (2.1%) showed a significant acute intracranial process. The NOC was positive in 6 of the 7 cases (sensitivity 85.7% and specificity 23.8%); the other case had a significant coagulopathy. New Orleans Criteria or coagulopathy had 100% sensitivity and 23.4% specificity. Conclusions: Our findings show that use of the NOC to evaluate potential intracranial injury in inpatient falls is limited. Adding criteria to the NOC may improve its test characteristics, with a sensitivity of 100% for the NOC or coagulopathy, suggesting potential clinical utility

Is the new orleans criteria for head ct useful for inpatient falls?

Background: Inpatient falls are a patient safety concern in all healthcare facilities. There is currently limited data on the utility of head computed tomography (CT) for inpatient falls. The New Orleans Criteria (NOC) is a validated tool used to determine the appropriateness of neuroimaging in the emergency department after sustaining a fall with minor head injury. The NOC include minor head injury with one of the following; headache, vomiting, age above 60, drug or alcohol intoxication, anterograde amnesia, trauma above the clavicles, and seizure activity. The aim of this study was to evaluate the significance of inpatient falls and determine if the NOC could be applied to triage these patients. Methods: This study is a retrospective review of inpatient falls from a multi-center health system, which includes an urban tertiary teaching hospital, 3 suburban community hospitals, 1 inpatient psychiatric facility and 1 inpatient rehab. Patient safety data was queried for all inpatient falls, classified as with injury, from May 1, 2015 through April 30, 2016. Encounters were manually reviewed for demographic data, circumstances of fall, laboratory results, components of NOC, CT head orders and results. Outcomes of interest include a head CT with any abnormal findings or an acute intracranial process. Results: Inpatient falls over the 1-year period totaled 332. Of the cases reviewed, 57% received a head CT after sustaining a fall. There were 12 (3.6%) CTs that showed a significant finding, and of those 7 (2.1%) had an acute intracranial process. No patients required surgical intervention or had a fatality related to the fall. Details of each fall case with an acute intracranial process are listed in Table 1. 250 (75.3%) patients met at least 1 component of the NOC, with 161 (64.6% of NOC positive) receiving a head CT. The NOC was positive in 6 of the 7 cases, with the missing case having a significant coagulopathy. Test characteristics of the NOC with and without the addition of coagulopathy for acute intracranial process are listed in Table 2. Conclusions: The NOC has been demonstrated as an effective tool in the emergency room; however, based on our findings its utility to evaluate potential intracranial injury in patients with in-hospital falls is limited. Adding additional criteria to the NOC can improve its test characteristics, but was unable to achieve both high specificity and sensitivity. Further investigation is required to develop a method to appropriately triage patients with in-hospital falls for significant neurological injury

Padua to improve: Matching VTE risk stratificaiton tool to the ehr

Background: Risk stratifying patients for potential development of hospital-related venous thromboembolism (VTE) is an important aspect of inpatient safety and is recommended by current guidelines. Many risk stratification tools are cumbersome and require significant time to complete. Developments have been made to partially or fully automate risk stratification tools, however there are restrictions within the electronic health records (EHR) that can limit these opportunities or slightly skew the tools to not accurately represent the population. It is increasingly important to determine which tool fits with the information available if it is to be automated. Purpose: The aim of our project was to compare two different VTE risk stratification tools, Padua and IMPROVE, for their accuracy of predicting in-hospital VTE events to determine which would be most appropriate to incorporate in our electronic health record EHR. Description: A multidisciplinary team, including physicians, nurses, quality specialists, data analysts, and information technologists, was assembled to develop and verify an EHR embedded, automated VTE risk score. Padua was initially selected and built into the EHR, however, on validation, multiple data points of the tool were difficult to consistently confirm, such as mobility and recent trauma or surgery. To improve the use of the selected tool prior to hospital-wide implementation, the test characteristics of the IMPROVE score were subsequently evaluated using a retrospective review of information available in the EHR. A summary of the risk factors included in each score are listed in Table 1. The study population included patients admitted to general medicine units at an urban tertiary referral center and suburban community hospital between January 2014 and August 2016. Padua and IMPROVE scores were calculated for each patient and in-hospital VTE events were identified based on an internally validated diagnosis algorithm. Of 51,417 hospitalizations reviewed, 60.8% of the patients were categorized as low risk for VTE using the Padua score compared to 72.3% for IMPROVE. There was a total of 667 VTE events (1.3%). For both risk tools, the rate of in-hospital VTE events for the low risk population was 0.3%. The specificity for IMPROVE was significantly higher than the Padua (72.9% vs. 61.4%,

Missed and refused chemoprophylaxis: What is the impact on VTE?

Background: Chemoprophylaxis with subcutaneous heparin or low-molecular weight heparin is recommended for venous thromboembolism (VTE) prevention in appropriate medical patients. However, all doses are not always administered and the consequences are unclear. We sought to determine if there is a relationship between missed and/or refused doses and development of in-hospital VTEs. Methods: The study is a retrospective analysis of patients discharged from general medicine units at an 800-bed urban tertiary referral center and an affiliated 200-bed suburban hospital from January 1, 2014 through August 10, 2016. Patients with a length of stay of at least 2 days were included in the analysis. Chemoprophylaxis doses were subcutaneous heparin 5000 units twice or three times daily and subcutaneous enoxaparin 40 mg or 30 mg daily. Doses that the patient did not received were categorized as either refused, which required explicit documentation of refusal, or missed. In-hospital VTE events were identified by a validated diagnosis algorithm using medication administration records and problem list documentation within the electronic health record. Patients with VTE receiving anticoagulation at time of presentation or within the first 24 hours of hospitalization were also excluded. Baseline VTE risk was calculated using the IMPROVE risk assessment model where scores of \u3e1 represent high risk, which includes age \u3e60 years (1), active cancer (1), prior VTE (2), and hypercoagulable condition (2). Other potential VTE risk factors of length of stay and central venous catheters, including peripherally inserted central catheters, were also evaluated. Univariate and multivariate regression analyses were performed using SAS. Results: 460 in-hospital VTE events occurred in 32,358 hospitalizations (1.42%). 51.3% received all doses, 23.7% only refused, and 25.0% missed a dose for any other reason. In univariate analysis, patients with any missed heparin or enoxaparin had higher odds of VTE than those who received all doses (1.73, 95% CI 1.43-2.10), and those who only refused had lower odds (0.26, 95% CI 0.18-0.39). The relationship between chemoprophylaxis administration and outcomes persisted across the spectrum of IMPROVE scores (Figure 1). On multivariate analysis, including the additional risk factors, the odds of VTE with missed doses was no longer significant, however, the significance remained for refused (Table 1).Conclusions: Administration of prescribed VTE chemoprophylaxis is an important step in VTE prevention, however patient who missed at least one dose during their hospitalization did not have a higher incidence of in-hospital VTE, when adjusted for risk factors, while patients who only refused doses were actually at a significantly lower risk. The mechanism for lower VTE rates in refusal patient remains unclear

Putting the shm key principles into practice: Direct objective clinical evaluation of new-hire hospitalists to improve physician communication and engagement while fulfilling fppe

Background: SHM Key Characteristic 9.1 on patient centered care encourages using guidelines/checklists to reinforce effective communication. Focused practice performance evaluations (FPPE) are a required regulatory hospital process for new medical staff members. In cognitive specialties, such as hospital medicine, completing an objective assessment of clinical skills can be difficult, with most initial evaluations based on more subjective performance assessments completed by peers or ancillary staff, which can be inconsistent across environments and personnel. Purpose: We sought to develop and implement an objective clinical assessment tool for initial FPPE of new hires in a multi-site hospital medicine group to reinforce clinical communication guidelines. Description: After developing divisional evidence based clinical communication guidelines for hospitalists in 2015, an assessment tool was designed based on the already validated SEGUE framework, a communication checklist commonly used in medical education, containing the domains of Set the stage, Elicit information, Give information, Understand the patient’s perspective, and End the encounter. The core SEGUE tool was selected for use in the inpatient environment along with a general comment area to evaluate other observed communication/safety behaviors as it aligned with the hospital medicine group’s clinical communication guidelines reinforcing AIDET (Acknowledge, Introduce, Duration, Explain, Thank You). Using an online survey service, the tool was available electronically, so that it could be used remotely by all authorized users on a variety of devices, including smartphones (Figure 1). After a 2 hour training session of observers, assessments were conducted at the bedside primarily in the direct care clinical environment. A majority of the observations were made on all new hires by the division head to create a level of inter-subject reliability for ratings, and so the division head could directly interact with all new staff. Additional observations were made by the section head at each specific clinical campus. A total of at least 5 observations were made for each subject. Formative feedback was given immediately to the subject hospitalist after each encounter and a summative feedback on the experience was provided to the new hire. The results were also reviewed in the new hire’s formal performance evaluation within approximately 6 months with the division head. Informal feedback from new hires on the observation process was positive, and it also helped to identify opportunities for workflow improvement as divisional leadership was able to more closely observe bedside activities. After successful completion of the first cohort in 2015, a second cohort is being evaluated during the latter half of 2016. To date, over 140 assessments have been performed on over 30 new hire hospitalists. Information from these assessments allowed our group to assess opportunities for continued training and improvement. We plan to correlate observation assessment results with patient experience scores, physician engagement, and staff retention.Conclusions: The use of a modified SEGUE framework adapted for the inpatient setting and operationalized on an online survey service, allowed for an objective evaluation of new hire hospitalists across multiple clinical settings, with completion of requirements for FPPE and generation of meaningful feedback to the hospitalists on their communication with patients