Validation of a Screening Risk Index for Serious Prescription Opioid-Induced Respiratory Depression or Overdose in a US Commercial Health Plan Claims Database.

Objective: To validate a risk index that estimates the likelihood of overdose or serious opioid-induced respiratory depression (OIRD) among medical users of prescription opioids. Subjects and Methods: A case-control analysis of 18,365,497 patients with an opioid prescription from 2009 to 2013 in the IMS PharMetrics Plus commercially insured health plan claims database (CIP). An OIRD event occurred in 7,234 cases. Four controls were selected per case. Validity of the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (RIOSORD), developed previously using Veterans Health Administration (VHA) patient data, was assessed. Multivariable logistic regression was used within the CIP study population to develop a slightly refined RIOSORD. The composition and performance of the CIP-based RIOSORD was evaluated and compared with VHA-based RIOSORD. Results: VHA-RIOSORD performed well in discriminating OIRD events in CIP (C-statistic = 0.85). Additionally, re-estimation of logistic model coefficients in CIP yielded a 0.90 C-statistic. The resulting comorbidity and pharmacotherapy variables most highly associated with OIRD and retained in the CIP-RIOSORD were largely concordant with VHA-RIOSORD. These variables included neuropsychiatric and cardiopulmonary disorders, impaired drug excretion, opioid characteristics, and concurrent psychoactive medications. The average predicted probability of OIRD ranged from 2% to 83%, with excellent agreement between predicted and observed incidence across risk classes. Conclusions: RIOSORD had excellent predictive accuracy in a large population of US medical users of prescription opioids, similar to its performance in VHA. This practical risk index is designed to support clinical decision-making for safer opioid prescribing, and its clinical utility should be evaluated prospectively.

In-vitro characterization of canine multipotent stromal cells isolated from synovium, bone marrow, and adipose tissue: a donor-matched comparative study.

BACKGROUND: The dog represents an excellent large animal model for translational cell-based studies. Importantly, the properties of canine multipotent stromal cells (cMSCs) and the ideal tissue source for specific translational studies have yet to be established. The aim of this study was to characterize cMSCs derived from synovium, bone marrow, and adipose tissue using a donor-matched study design and a comprehensive series of in-vitro characterization, differentiation, and immunomodulation assays. METHODS: Canine MSCs were isolated from five dogs with cranial cruciate ligament rupture. All 15 cMSC preparations were evaluated using colony forming unit (CFU) assays, flow cytometry analysis, RT-PCR for pluripotency-associated genes, proliferation assays, trilineage differentiation assays, and immunomodulation assays. Data were reported as mean ± standard deviation and compared using repeated-measures analysis of variance and Tukey post-hoc test. Significance was established at p < 0.05. RESULTS: All tissue samples produced plastic adherent, spindle-shaped preparations of cMSCs. Cells were negative for CD34, CD45, and STRO-1 and positive for CD9, CD44, and CD90, whereas the degree to which cells were positive for CD105 was variable depending on tissue of origin. Cells were positive for the pluripotency-associated genes NANOG, OCT4, and SOX2. Accounting for donor and tissue sources, there were significant differences in CFU potential, rate of proliferation, trilineage differentiation, and immunomodulatory response. Synovium and marrow cMSCs exhibited superior early osteogenic activity, but when assessing late-stage osteogenesis no significant differences were detected. Interestingly, bone morphogenic protein-2 (BMP-2) supplementation was necessary for early-stage and late-stage osteogenic differentiation, a finding consistent with other canine studies. Additionally, synovium and adipose cMSCs proliferated more rapidly, displayed higher CFU potential, and formed larger aggregates in chondrogenic assays, although proteoglycan and collagen type II staining were subjectively decreased in adipose pellets as compared to synovial and marrow pellets. Lastly, cMSCs derived from all three tissue sources modulated murine macrophage TNF-α and IL-6 levels in a lipopolysaccharide-stimulated coculture assay. CONCLUSIONS: While cMSCs from synovium, marrow, and adipose tissue share a number of similarities, important differences in proliferation and trilineage differentiation exist and should be considered when selecting cMSCs for translational studies. These results and associated methods will prove useful for future translational studies involving the canine model.

Combined tibial plateau levelling osteotomy and tibial tuberosity transposition for treatment of cranial cruciate ligament insufficiency with concomitant medial patellar luxation.

OBJECTIVES: To describe the surgical technique and report short-term outcome for combined tibial plateau levelling osteotomy and tibial tuberosity transposition (TPLO-TTT) as an option in the treatment of cranial cruciate ligament insufficiency with concomitant medial patellar luxation. METHODS: Medical records were reviewed (2011-2013) of dogs that underwent a standard tibial plateau levelling osteotomy followed by a tibial tuberosity transposition in the frontal plane and stabilized with pin and tension-band wire fixation as a component of surgical treatment for combined cranial cruciate ligament insufficiency and medial patellar luxation. Signalment, fixation method together with any ancillary procedures, function at the in-hospital follow-up examinations, and any complications were recorded. Healing was assessed retrospectively based on the grading criteria of the International Society Of Limb Salvage. RESULTS: Fifteen stifle joints in 11 dogs were identified; 13 stifles were available for in-hospital follow-up. All 13 achieved union (3 with grade III/IV and 10 with grade IV/IV radiographic healing scores); mean time to healing was 10.6 (± 2.9) weeks. Patellar ligament thickening was also identified radiographically in seven of the 13 of stifle joints. All dogs were reported to have mild or no lameness at their last follow-up examination. No catastrophic or major postoperative complications occurred that required additional surgery. Patellar re-luxation did not occur in any of the 13 stifles available for in-hospital follow-up. CLINICAL SIGNIFICANCE: The TPLO-TTT was found to be a reliable and effective technique when used as a part of the treatment of combined cranial cruciate ligament insufficiency with concomitant medial patellar luxation in this series of dogs.

Real-world glycemic outcomes in patients with type 2 diabetes initiating exenatide once weekly and liraglutide once daily: a retrospective cohort study.

AIM: The glucagon-like peptide-1 receptor agonists exenatide once weekly (QW) and liraglutide once daily (QD) have demonstrated improvements in glycemic outcomes in patients with type 2 diabetes mellitus in randomized clinical trials. However, little is known about their real-world comparative effectiveness. This retrospective cohort study used the Quintiles Electronic Medical Record database to evaluate the 6-month change in glycated hemoglobin (A1C) for patients initiating exenatide QW or liraglutide QD. METHODS: Patients with type 2 diabetes mellitus prescribed exenatide QW (n=664) or liraglutide QD (n=3,283) between February 1, 2012 and May 31, 2013 were identified. Baseline A1C measures were from 75 days before to 15 days after initiating exenatide QW or liraglutide QD, with follow-up measures documented at 6 months (±45 days). Adjusted linear regression models compared the difference in mean A1C change. A priori defined sensitivity analysis was performed in the subgroup of patients with baseline A1C ≥7.0% and no prescription for insulin during the 12-month pre-index period. RESULTS: For exenatide QW and liraglutide QD, respectively, mean (SD) age of the main study cohort was 58.01 (10.97) and 58.12 (11.05) years, mean (SD) baseline A1C was 8.4% (1.6) and 8.4% (1.6), and 48.2% and 54.2% of patients were women. In adjusted models, change in A1C did not differ between exenatide QW and liraglutide QD during 6 months of follow-up. Results were consistent in the subgroup analyses. CONCLUSION: In a real-world setting, A1C similarly improves in patients initiating exenatide QW or liraglutide QD.

Patient Perceptions of Patient-Centered Medical Home Characteristics and Satisfaction with Free Clinic Services.

The patient-centered medical home (PCMH) is a model of health care delivery designed to improve patient health outcomes by increasing the effectiveness of primary care. The effectiveness of PCMH on vulnerable populations is still largely unknown. The purpose of this study was to examine the relationship between patient perceptions of PCMH characteristics and patient satisfaction among Spanish-speaking and non-Spanish-speaking patients receiving health care at free clinics. A self-administered survey was used to collect data in 2 free clinics in the United States in 2013. Patients were primarily young and female; 44% were Spanish speaking. Patient perceptions of PCMH characteristics were assessed using multi-item Consumer Assessment of Healthcare Providers and Systems scales developed by the Agency for Healthcare Research and Quality. Patient satisfaction was assessed as satisfaction with care received at the clinic and willingness to recommend the provider. Multivariate logistic regression modeled the association between PCMH components and these 2 patient satisfaction measures. In adjusted analyses among Spanish speakers, satisfaction with clinic care was associated with staff helpfulness (OR = 6.03, 95% CI = 1.87-19.46) and no perceived discrimination (OR = 2.55, 95% CI = 1.22-5.33). For non-Spanish speakers, provider communication and politeness significantly increased odds of satisfaction with clinic services. Provider communication was strongly associated with patients' intention to recommend the provider to others for both Spanish speakers and non-Spanish speakers (OR = 4.83, 95% CI = 1.35-17.24; OR = 5.42, 95% CI = 1.54-19.09, respectively). Findings suggest that interpersonal characteristics of providers and clinic staff are critical to patient satisfaction among vulnerable populations served by free clinics. Future studies should examine PCMH components and clinical outcomes among this population.

Impact of surgical site infections on length of stay and costs in selected colorectal procedures.

BACKGROUND: Length of stay (LOS) and inpatient costs for open-abdomen colorectal procedures have not been examined recently. The aim of this study was to determine LOS and costs for several colorectal procedures in the context of factors potentially associated with surgical site infection (SSI). METHODS: We used a large U.S. hospital database to identify the variables associated with longer LOS and higher costs for colorectal procedures from January 1, 2005, through June 30, 2006. The study population consisted of all patients >18 years, identified via International Classification of Disease, Ninth Revision, procedural codes for elective colorectal surgery. Patient demographics, surgical procedure, and a modified Study of the Efficacy of Nosocomial Infection Control (SENIC) infection risk score were examined using logistic regression as predictors of LOS >or=1 week and cost >or=$15,000. Patients given cefotetan as surgical prophylaxis were compared with patients given cefazolin/metronidazole. Superficial and deep SSIs were considered; intra-abdominal infection was not. RESULTS: The 25,825 patients were of average age 63 years, with 53% being female and 75% being Caucasian. The overall infection rate was 3.7%. The mean LOS was 7.25 days, and the mean +/- standard deviation total cost per patient $13,746 +/- $13,330. Rates of infection, LOS, and mean hospital costs were all greater for patients with a high SENIC score and increasing disease acuity. Values for these outcome variables were highest for procedures involving stoma formation, followed by operations on the small bowel and large bowel. Variables independently predictive of longer LOS were SSI (odds ratio [OR] 11.74; 95% confidence interval [CI] 9.67, 14.26), age >or=65 years (OR 1.90; 95% CI 1.81, 2.01), and high SENIC score (OR 1.79; 95% CI 1.67, 1.92), whereas Caucasian race (OR 0.86; 95% CI 0.81, 0.91) was predictive of a shorter LOS. Cefazolin/metronidazole was not predictive of a shorter LOS compared with cefotetan (OR 1.06; 95% CI 0.96, 1.17) but was associated with significantly more hospitalizations with costs >or=$15,000 (OR 1.39; 95% CI 1.23, 1.56). CONCLUSIONS: Length of stay and cost rise proportionally with SENIC score, disease acuity, and patient characteristics such as age. Surgical site infections are significantly and independently associated with LOS and cost and contribute to inpatient morbidity and expense. Cefotetan has limited availability, and substitutions are utilized increasingly. Although equally efficacious in elective colon procedures, cefotetan used as surgical prophylaxis was associated with lower hospitalization costs than cefazolin plus metronidazole.

Economic burden of postoperative ileus associated with colectomy in the United States.

BACKGROUND: Postoperative ileus, a transient impairment of gastrointestinal motility, is a common cause of delay in return to normal bowel function after abdominal surgery. Colectomy surgery patients who develop postoperative ileus could have greater health care resource utilization, including prolonged hospitalization, compared with those who do not develop postoperative ileus. Very few studies have assessed the impact of postoperative ileus on resource utilization and costs using retrospective analysis of administrative databases. OBJECTIVE: To assess health care utilization and costs in colectomy surgery patients who developed postoperative ileus versus those who did not. METHODS: A retrospective cohort study design was used. Adult patients with a principal procedure code for colectomy (ICD-9-CM procedure codes 45.71-45.79), discharged between January 1, 2004, and December 31, 2004, were identified from the Premier Perspective database of inpatient records from more than 500 hospitals in the United States. The colectomy patients were further classified for the presence of postoperative ileus, identified by the presence, in any diagnosis field on the administrative patient records, of a code for paralytic ileus (ICD-9-CM code 560.1) and/or digestive system complications (ICD-9-CM code 997.4) during the inpatient stay. Code 997.4 was used to account for cases in which postoperative ileus would be reported as a complication of anastomosis, as could be the case in colectomy surgeries. Hospital length of stay (LOS) and hospitalization costs were compared using t-tests. Multivariate analyses were performed with log-transformed LOS and log-transformed cost as the dependent variables. Patient demographics, mortality risk, disease severity, admission source, payment type (retrospective/prospective), and hospital characteristics were used as covariates. RESULTS: A total of 17,876 patients with primary procedure code for colectomy were identified, of whom 3115 (17.4%) patients were classified for presence of postoperative ileus (including paralytic ileus only [n=1216; 6.8%], digestive system complications only [n=383; 2.1%], or both [n=1516; 8.5%]). A majority of the colectomy patients with and without postoperative ileus, respectively, were male (54.1% vs. 50.3%, P < 0.001), Caucasian (70.5% vs. 69.3%, P = 0.170), and aged 51-64 years (51.1% vs. 49.7%, P = 0.143). The mean [SD] hospital LOS was significantly longer in patients with postoperative ileus (13.8 [13.3] days) compared with patients without postoperative ileus (8.9 [9.5] days; P < 0.001). Presence of postoperative ileus was found to be a significant predictor of LOS (P < 0.001) in the regression model, controlling for covariates. Female gender (P = 0.002), greater severity level (P < 0.001), and hospital bed size of more than 500 (P = 0.013) were other significant predictors of hospital LOS. Presence of postoperative ileus was found to be a significant predictor of hospitalization costs (P < 0.001), controlling for covariates. CONCLUSION: Postoperative ileus in colectomy patients is a significant predictor of hospital resource utilization.

Burden of blood transfusion in knee and hip surgery in the US and Belgium.

OBJECTIVE: Transfusion services in orthopaedic surgery can lead to unnecessary complications and increased healthcare costs. The objective of this study was to assess treatments and costs associated with blood and blood product transfusions in a historical cohort of 189,457 inpatients in the US and 34,987 inpatients in Belgium undergoing knee or hip surgery. METHODS: Descriptive analysis, logistic regression and ordinary least squares regression were used to describe the factors associated with the use and cost of allogeneic blood transfusion. RESULTS: Hospitalisation costs for joint replacement surgery totalled $12,718 (SD=6,356) and averaged 4.33 days in the US, while costs in Belgium were $6,526 (SD=3,192) and averaged 17.1 days. The use of low molecular weight heparin and tranexamic acid was much higher in Belgium than the US (36% and 99% compared to 0% and 40%, respectively). Patients in the US spent 12.7 (p<0.0001) fewer days in the hospital, 0.3 (p<0.0001) fewer days in the intensive care unit and were 88% less likely to have allogeneic blood transfusions (OR=0.22, 95% CI 0.22-0.23), but incurred $6,483 (p<0.0001) more costs per hospitalisation than patients in Belgium. CONCLUSIONS: While hospital costs for patients were greater in the US, length of stay was shorter and patients were less likely to have transfusion services than those patients in Belgium. While this study is limited by factors inherent to observational studies, such as omitted variable bias, misclassification, and disease comorbidity, there are substantial differences in the use of blood products between Belgium and the US.

Comparison between spinal surgery blood transfusion services costs and associated treatment practices in the United States and Belgium.

OBJECTIVE: This study assessed utilization and cost of allogeneic blood transfusion (ABT) associated with spinal surgery in the United States (US) and Belgium. METHODS: A retrospective cohort of 292,864 spinal surgery inpatients in US hospitals was pooled with a cohort of 27,952 inpatients who had similar procedures in Belgian hospitals. Utilization and cost data were derived from hospital accounting systems. Costs were converted to US dollars. Descriptive and multivariate statistics were used to describe the factors associated with the use and cost of ABT. Missing data, confounding, and variable measurement error were addressed using standard approaches for observational studies. RESULTS: US hospitalizations cost $12,044 (SD = 15,920) over 3.6 days compared to $4010 (SD = 3586) over 10.3 days in Belgium. Low molecular weight heparin was used by 78% of Belgian patients and 4% of US patients. Red blood cell utilization occurred in approximately 7% of patients from both countries; however US patients received 6 units compared to 3 units by Belgian patients. US patients spent 3.5 (p < 0.0001) less days in hospital, 1.0 (p < 0.0001) more days in an intensive care unit, used 64% more allogeneic blood (OR = 1.64, 95% CI 1.53-1.75), and incurred $13,647 (p < 0.0001) more per hospitalization than Belgian patients. CONCLUSIONS: US patients used more blood products, had shorter hospital stays, and incurred greater costs than Belgian patients. Specialists as attending physicians were associated with lower utilization of ABT; this may be an administrative change that hospitals can implement to reduce utilization and costs.

Effects of ECT on Polysomnographic Sleep: A Prospective Investigation.

The authors describe a pilot investigation using ambulatory polysomnography (PSG) to assess rapid eye movement (REM) latency in 11 depressed inpatients before and after a course of electroconvulsive therapy (ECT). Prior to beginning ECT, all subjects had REM latencies of 56 minutes or less (mean 22 min). A course of ECT was associated with clinical improvement in every patient and a statistically significant (p < 0.0002) increase of 67% in mean REM latency (37 min). However, individual patients showed marked variability in REM latency both during and after the course of ECT, and 7 of the 11 responders continued to exhibit shortened REM latencies of 34 min or less. Technical considerations related to PSG studies during ECT are reviewed and the clinical and theoretical implications of our findings are discussed.