Retrospective Comparative Analysis of Opioid Use and Intra-Articular Corticosteroid Injections Before and After Initial Treatment of Knee Osteoarthritis with Hylan G-F 20.

BACKGROUND: Knee osteoarthritis (OA) is a painful condition affecting >250 million people worldwide and is a leading cause of disability. Intra-articular (IA) corticosteroids and/or oral opioids are often recommended for the management of knee OA pain. There are, however, concerns regarding their safety and tolerability. STUDY QUESTION: Do patients diagnosed with knee OA show a decrease in opioids or IA corticosteroid injections prescribed/administered in hospitals following hylan G-F 20 treatment? STUDY DESIGN: This case-crossover, retrospective study using Health Facts®, a de-identified electronic health records database, enrolled patients ≥18 years with knee OA treated with hylan G-F 20 between January 1, 2000 and March 31, 2016, with data within 6 months before/after treatment. MEASURES AND OUTCOMES: Primary endpoints compared days on opioids, amounts of opioids, and number of IA corticosteroid injections before/after hylan G-F 20 treatment via paired t-tests. RESULTS: A total of 513 patients were qualified for analysis. In the opioid cohort, the average total number of days on opioids (N = 50; 5.0 vs 13.5 days; P = 0.007) and average total amount of opioids (N = 44; 165.4 morphine mg equivalents [MME] vs 493.7 MME; P = 0.013) were lower 6 months after hylan G-F 20 treatment than 6 months before treatment. In the IA corticosteroid cohort, the average number of IA corticosteroid injections decreased after hylan G-F 20 treatment (N = 36; 0.56 in the 6-month follow-up vs 1.39 before treatment; P < 0.0001). Additional time frames of 1-5 months before and after treatment were examined; similar conclusions were drawn for patients with >2 months of data. CONCLUSION: Patients with knee OA previously treated with opioids or IA corticosteroid injections who received hylan G-F 20 demonstrated statistically significant decreases in these medications >2 months following hylan G-F 20 treatment versus >2 months before treatment.

Analysis of predictors of opioid-free analgesia for management of acute post-surgical pain in the United States.

OBJECTIVES: Utilization of opioid-free analgesia (OFA) for post-surgical pain is a growing trend to counter the risks of opioid abuse and opioid-related adverse drug events (ORADEs). However, utilization patterns of OFA have not been examined. In this study, we investigated the utilization patterns and predictors of OFA in a surgical population in the United States. METHODS: Analysis of the Cerner Health Facts database (January 2011 to December 2015) was conducted to describe hospital and patient characteristics associated with OFA. Baseline characteristics, such as age, gender, race, discharge status, year of admission and chronic comorbidities at index admission were collected. Hospital characteristics and payer type at index admission were collected as reported in the electronic health record database. Descriptive statistics and logistic regression were used to identify statistically significant predictors of OFA on patient and institutional levels. RESULTS: The study identified 10,219 patients, from 187 hospitals, who received post-surgical OFA and 255,196 patients who received post-surgical opioids. OFA rates varied considerably by hospital. Patients more likely to receive OFA were older (OR = 1.06, 95% CI [1.03, 1.10]; p < .001), or had neurological disorders (OR = 1.24, 95% CI [1.10, 1.39]; p < .001), diabetes (OR = 1.20, 95% CI [1.08, 1.33]; p = .001) or psychosis (OR = 1.18, 95% CI [1.01, 1.37]; p = .030). Patients with obesity and depression were less likely to receive OFA (OR = 0.80, 95% CI [0.67, 0.95]; p = .010 OR = 0.85, 95% CI [0.73, 0.98]; p = .030, respectively). CONCLUSIONS: Use of post-surgical OFA was limited overall and was not favored in some patient groups prone to ORADEs, indicating missed opportunities to reduce opioid use and ORADE incidence. A substantial proportion of OFA patients was contributed by a few hospitals with especially high rates of OFA, suggesting that hospital policies, institutional structure and cross-functional departmental commitment to reducing opioid use may play a large role in the implementation of OFA.

The relationship between ICU hypotension and in-hospital mortality and morbidity in septic patients.

PURPOSE: Current guidelines recommend maintaining a mean arterial pressure (MAP) ≥ 65 mmHg in septic patients. However, the relationship between hypotension and major complications in septic patients remains unclear. We, therefore, evaluated associations of MAPs below various thresholds and in-hospital mortality, acute kidney injury (AKI), and myocardial injury. METHODS: We conducted a retrospective analysis using electronic health records from 110 US hospitals. We evaluated septic adults with intensive care unit (ICU) stays ≥ 24 h from 2010 to 2016. Patients were excluded with inadequate blood pressure recordings, poorly documented potential confounding factors, or renal or myocardial histories documented within 6 months of ICU admission. Hypotension exposure was defined by time-weighted average mean arterial pressure (TWA-MAP) and cumulative time below 55, 65, 75, and 85 mmHg thresholds. Multivariable logistic regressions determined the associations between hypotension exposure and in-hospital mortality, AKI, and myocardial injury. RESULTS: In total, 8,782 patients met study criteria. For every one unit increase in TWA-MAP < 65 mmHg, the odds of in-hospital mortality increased 11.4% (95% CI 7.8%, 15.1%, p < 0.001); the odds of AKI increased 7.0% (4.7, 9.5%, p < 0.001); and the odds of myocardial injury increased 4.5% (0.4, 8.7%, p = 0.03). For mortality and AKI, odds progressively increased as thresholds decreased from 85 to 55 mmHg. CONCLUSIONS: Risks for mortality, AKI, and myocardial injury were apparent at 85 mmHg, and for mortality and AKI risk progressively worsened at lower thresholds. Maintaining MAP well above 65 mmHg may be prudent in septic ICU patients.

Reduction in laboratory turnaround time decreases emergency room length of stay.

OBJECTIVE: Laboratory tests are an important contributor to treatment decisions in the emergency department (ED). Rapid turnaround of laboratory tests can optimize ED throughout by reducing the length of stay (LOS) and improving patient outcomes. Despite evidence supporting the effect of shorter turnaround time (TAT) on LOS and outcomes, there is still a lack of large retrospective studies examining these associations. Here, we evaluated the effect of a reduction in laboratory TAT on ED LOS using retrospective analysis of Electronic Health Records (EHR). MATERIALS AND METHODS: Retrospective analysis of ED encounters from a large, US-based, de-identified EHR database and a separate analysis of ED encounters from the EHR of an ED at a top-tier tertiary care center were performed. Additionally, an efficiency model calculating the cumulative potential LOS time savings and resulting financial opportunity due to laboratory TAT reduction was created, assuming other factors affecting LOS are constant. RESULTS: Multivariate regression analysis of patients from the multisite study showed that a 1-minute decrease in laboratory TAT was associated with 0.50 minutes of decrease in LOS. The single-site analysis confirmed our findings from the multisite analysis that a positive correlation between laboratory TAT and ED LOS exists in the ED population as a whole, as well as across different patient acuity levels. In addition, based on the calculations from the efficiency model, for a 5-, 10- and 15-minute TAT reduction, the single-site ED can potentially admit a total of 127, 256 and 386 additional patients, respectively, annually. CONCLUSION: A positive correlation between laboratory TAT and ED LOS was observed in a broad patient population and across distinct acuity levels.

Improved Outcomes Associated With the Use of Intravenous Acetaminophen for Management of Acute Post-Surgical Pain in Cesarean Sections and Hysterectomies.

BACKGROUND: Post-surgical pain impacts many patient outcomes. Effective pain management increasingly relies on multimodal analgesia regimens in which acetaminophen (APAP) is a key component. The aim of our study was to examine the impact of oral APAP versus intravenous (IV) APAP as a component of post-surgical pain management after Cesarean sections and hysterectomies. METHODS: A retrospective analysis of the Cerner HealthFacts® database (from January, 2011 to December, 2015) was conducted to compare outcomes of Cesarean section and hysterectomy surgery patients who received oral APAP to those who received IV APAP post-surgically. Length of stay (LOS), daily morphine milligram equivalent (MME) consumption, the presence of potential opioid-related adverse events (ORADEs), and total pharmacy costs were assessed. Adjusted results were derived using inverse probability weighted regression adjustment (IPW-RA) estimators based on covariates that included demographics, comorbidities, patient clinical characteristics, and hospital characteristics. RESULTS: The study identified 29,124 Cesarean section patients (24,612 oral APAP; 4,512 IV APAP) and 9,767 hysterectomy surgery patients (5,586 oral APAP; 4,181 IV APAP). Compared to the oral APAP group, the IV APAP group had reductions in adjusted LOS (Cesarean section: -11.7% days (P < 0.001), hysterectomy: -11.8% days (P = 0.005)), lowered adjusted daily MME consumption from day 0 to day 3 (Cesarean section: -1.6 mg (P < 0.001), hysterectomy: -1.7 mg (P = 0.014)), and reduced risk of ORADEs for Cesarean sections (relative risk of 0.45, P < 0.001). Total pharmacy costs were not significantly different between the two APAP groups. CONCLUSIONS: Post-surgical pain managed with IV APAP in patients undergoing Cesarean section or hysterectomy was associated with shorter LOS, reduced risk of ORADEs, and lower opioid consumption compared to patients managed with oral APAP, without adversely impacting total pharmacy costs.

Impact of Fluid Choice in Systemic Inflammatory Response Syndrome Patients on Hospital Cost Savings.

BACKGROUND: There is growing evidence of the benefits of intravenous fluid therapy with balanced crystalloids over 0.9% 'normal' saline. This analysis evaluated the economic impact of increasing usage of a calcium-free balanced crystalloid solution (BAL) in patients with systemic inflammatory response syndrome (SIRS) on an annual hospital budget. METHODS: An Excel®-based economic model was developed to estimate costs associated with increased BAL usage (i.e., use in a greater proportion of patients), from the US hospital perspective, over a 5-year time horizon. Clinical inputs were based on the results of a retrospective Electronic Health Record (EHR) database analysis identifying significantly fewer complications among SIRS patients receiving predominantly BAL versus saline. Complication-associated costs, adjusted to 2015, were obtained from published reports. Scenario analyses examined cost impacts for hospitals of various sizes, with different BAL adoption levels and rates. RESULTS: Base-case scenario analysis (300-bed hospital, 80% occupancy, current and year 5 BAL usage in 5 and 75% of SIRS patients, respectively, exponential year-over-year adoption) showed year 1 hospital savings of US$29,232 and cumulative 5-year savings of US$1.16M. Cumulative 5-year pharmacy savings were US$172,641. Scenario analyses demonstrated increasing cumulative 5-year savings with increasing hospital size, year 5 BAL usage in greater proportions of patients, and rapid/early BAL adoption. CONCLUSIONS: Increased BAL usage represents an opportunity for hospitals and pharmacy departments to reduce complication-related costs associated with managing SIRS patients. The model suggests that savings could be expected across a range of scenarios, likely benefiting hospitals of various sizes and with different adoption capabilities.

The economic impact of poor sample quality in clinical chemistry laboratories: results from a global survey.

Background Despite advances in clinical chemistry testing, poor blood sample quality continues to impact laboratory operations and the quality of results. While previous studies have identified the preanalytical causes of lower sample quality, few studies have examined the economic impact of poor sample quality on the laboratory. Specifically, the costs associated with workarounds related to fibrin and gel contaminants remain largely unexplored. Methods A quantitative survey of clinical chemistry laboratory stakeholders across 10 international regions, including countries in North America, Europe and Oceania, was conducted to examine current blood sample testing practices, sample quality issues and practices to remediate poor sample quality. Survey data were used to estimate costs incurred by laboratories to mitigate sample quality issues. Results Responses from 164 participants were included in the analysis, which was focused on three specific issues: fibrin strands, fibrin masses and gel globules. Fibrin strands were the most commonly reported issue, with an overall incidence rate of ∼3%. Further, 65% of respondents indicated that these issues contribute to analyzer probe clogging, and the majority of laboratories had visual inspection and manual remediation practices in place to address fibrin- and gel-related quality problems (55% and 70%, respectively). Probe maintenance/replacement, visual inspection and manual remediation were estimated to carry significant costs for the laboratories surveyed. Annual cost associated with lower sample quality and remediation related to fibrin and/or gel globules for an average US laboratory was estimated to be $100,247. Conclusions Measures to improve blood sample quality present an important step towards improved laboratory operations.

Impact of intravenous fluid composition on outcomes in patients with systemic inflammatory response syndrome.

INTRODUCTION: Intravenous (IV) fluids may be associated with complications not often attributed to fluid type. Fluids with high chloride concentrations such as 0.9 % saline have been associated with adverse outcomes in surgery and critical care. Understanding the association between fluid type and outcomes in general hospitalized patients may inform selection of fluid type in clinical practice. We sought to determine if the type of IV fluid administered to patients with systemic inflammatory response syndrome (SIRS) is associated with outcome. METHODS: This was a propensity-matched cohort study in hospitalized patients receiving at least 500 mL IV crystalloid within 48 hours of SIRS. Patient data was extracted from a large multi-hospital electronic health record database between January 1, 2009, and March 31, 2013. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay, readmission, and complications measured by ICD-9 coding and clinical definitions. Outcomes were adjusted for illness severity using the Acute Physiology Score. Of the 91,069 patients meeting inclusion criteria, 89,363 (98%) received 0.9% saline whereas 1706 (2%) received a calcium-free balanced solution as the primary fluid. RESULTS: There were 3116 well-matched patients, 1558 in each cohort. In comparison with the calcium-free balanced cohort, the saline cohort experienced greater in-hospital mortality (3.27% vs. 1.03%, P <0.001), length of stay (4.87 vs. 4.38 days, P = 0.016), frequency of readmission at 60 (13.54 vs. 10.91, P = 0.025) and 90 days (16.56 vs. 12.58, P = 0.002) and frequency of cardiac, infectious, and coagulopathy complications (all P < 0.002). Outcomes were defined by administrative coding and clinically were internally consistent. Patients in the saline cohort received more chloride and had electrolyte abnormalities requiring replacement more frequently (P < 0.001). No differences were found in acute renal failure. CONCLUSIONS: In this large electronic health record, the predominant use of 0.9% saline in patients with SIRS was associated with significantly greater morbidity and mortality compared with predominant use of balanced fluids. The signal is consistent with that reported previously in perioperative and critical care patients. Given the large population of hospitalized patients receiving IV fluids, these differences may confer treatment implications and warrant corroboration via large clinical trials. TRIAL REGISTRATION: NCT02083198 clinicaltrials.gov; March 5, 2014.

Structural reorganization triggered by charging of Lys residues in the hydrophobic interior of a protein.

Structural consequences of ionization of residues buried in the hydrophobic interior of proteins were examined systematically in 25 proteins with internal Lys residues. Crystal structures showed that the ionizable groups are buried. NMR spectroscopy showed that in 2 of 25 cases studied, the ionization of an internal Lys unfolded the protein globally. In five cases, the internal charge triggered localized changes in structure and dynamics, and in three cases, it promoted partial or local unfolding. Remarkably, in 15 proteins, the ionization of the internal Lys had no detectable structural consequences. Highly stable proteins appear to be inherently capable of withstanding the presence of charge in their hydrophobic interior, without the need for specialized structural adaptations. The extent of structural reorganization paralleled loosely with global thermodynamic stability, suggesting that structure-based pK(a) calculations for buried residues could be improved by calculation of thermodynamic stability and by enhanced conformational sampling.

The 1.75 Å resolution structure of fission protein Fis1 from Saccharomyces cerevisiae reveals elusive interactions of the autoinhibitory domain.

Fis1 mediates mitochondrial and peroxisomal fission. It is tail-anchored to these organelles by a transmembrane domain, exposing a soluble cytoplasmic domain. Previous studies suggested that Fis1 is autoinhibited by its N-terminal region. Here, a 1.75 Å resolution crystal structure of the Fis1 cytoplasmic domain from Saccharomyces cerevisiae is reported which adopts a tetratricopeptide-repeat fold. It is observed that this fold creates a concave surface important for fission, but is sterically occluded by its N-terminal region. Thus, this structure provides a physical basis for autoinhibition and allows a detailed examination of the interactions that stabilize the inhibited state of this molecule.

Molecular determinants of the pKa values of Asp and Glu residues in staphylococcal nuclease.

Prior computational studies of the acid-unfolding behavior of staphylococcal nuclease (SNase) suggest that the pK(a) values of its carboxylic groups are difficult to reproduce with electrostatics calculations with continuum methods. To examine the molecular determinants of the pK(a) values of carboxylic groups in SNase, the pK(a) values of all 20 Asp and Glu residues were measured with multidimensional and multinuclear NMR spectroscopy in an acid insensitive variant of SNase. The crystal structure of the protein was obtained to describe the microenvironments of the carboxylic groups. Fourteen Asp and Glu residues titrate with relatively normal pK(a) values that are depressed by less than 1.1 units relative to the normal pK(a) of Asp and Glu in water. Only six residues have pK(a) values shifted by more than 1.5 units. Asp-21 has an unusually high pK(a) of 6.5, which is probably the result of interactions with other carboxylic groups at the active site. The most perturbed pK(a) values appear to be governed by hydrogen bonding and not by Coulomb interactions. The pK(a) values calculated with standard continuum electrostatics methods applied to static structures are more depressed than the measured values because Coulomb effects are exaggerated in the calculations. The problems persist even when the protein is treated with the dielectric constant of water. This can be interpreted to imply that structural relaxation is an important determinant of the pK(a) values; however, no major pH-sensitive conformational reorganization of the backbone was detected using NMR spectroscopy.