Perioperative Fluid Utilization Variability and Association With Outcomes: Considerations for Enhanced Recovery Efforts in Sample US Surgical Populations.

OBJECTIVES: To study current perioperative fluid administration and associated outcomes in common surgical cohorts in the United States. BACKGROUND: An element of enhanced recovery care protocols, optimized perioperative fluid administration may be associated with improved outcomes; however, there is currently no consensus in the United States on fluid use or the effects on outcomes of this use. METHODS: The study included all inpatients receiving colon, rectal, or primary hip or knee surgery, 18 years of age or older, who were discharged from a hospital between January 1, 2008 and June, 30 2012 in the Premier Research Database. Patient outcomes and intravenous fluid utilization on the day of surgery were summarized for each surgical cohort. Regression models were developed to evaluate associations of high or low day-of-surgery fluids with the likelihood of increased hospital length of stay (LOS), total costs, or postoperative ileus. RESULTS: The study showed significant associations between high fluid volume given on the day of surgery with both increased LOS (odds ratio 1.10-1.40) and increased total costs (odds ratio 1.10-1.50). High fluid utilization was associated with increased presence of postoperative ileus for both rectal and colon surgery patients. Low fluid utilization was also associated with worse outcomes. CONCLUSIONS: According to results from this review of current practice in US hospitals, fluid optimization would likely lead to decreased variability and improved outcomes.

Patient Outcomes on Day 4 of Intravenous Antibiotic Therapy in Non-Intensive Care Unit Hospitalized Adults With Community-Acquired Bacterial Pneumonia.

BACKGROUND: Community-acquired bacterial pneumonia (CABP) is a leading cause of morbidity and mortality especially in hospitalized patients. In place of clinical end points traditionally used to evaluate antimicrobial efficacy for its treatment, Food and Drug Administration guidelines now require all registration trials to assess clinical response at day 4. The primary objective of this study was to assess health outcomes (length of stay [LOS] and hospital charges) between responders and nonresponders at this time point. METHODS: The Premier database was used to identify adult patients from 4 participating hospitals with a principal diagnosis of CABP (International Classification of Diseases, Ninth Revision, Clinical Modification, codes 481, 482.0, 483.8, 484.3, 484.5, 485, 486, or 487.0) hospitalized between July 1, 2010, and June 30, 2011. Only non-intensive care unit patients with hospital stays exceeding 2 days and receiving intravenous antibiotic agents within 24 hours of admission were included. After institutional review board approvals, a retrospective chart review extracted data for patient demographics, clinical efficacy variables at day 4, LOS, and total hospital charges. Data analysis included multivariable gamma regression models to control for patient demographics and clinical differences between responders and nonresponders. RESULTS: A total of 666 patients met study the criteria. Mean (SD) age was 70.7 (17.9) years, and 42.5% were males. Among these patients, 277 (41.6%) achieved clinical response by day 4 of initial antibiotic therapy. The unadjusted mean (SD) LOS was 6.3 (2.8) days for responders and 7.4 (5.6) days for nonresponders (P = 0.0009). Respective unadjusted total hospital charges were $22,827 (SD, $17,724) and $26,403 ($36,882) (P = 0.0031). Adjusted for demographics and clinical factors, nonresponders compared with responders had an increased LOS of 0.9 days (8.4 vs 7.5 days; P = 0.0008), resulting in associated charges of approximately $2500 ($34,139 vs $36,629; P = 0.0768). CONCLUSIONS: In this real-world chart study, less than half of hospitalized patients with CABP achieved clinical response at day 4 of initial intravenous antibiotic therapy. The observed clinical response was associated with a significantly shorter hospital stay and trended toward lower total hospital charges. These findings corroborate the Food and Drug Administration guidance for assessing antimicrobial therapy at day 4 because responder is associated with improved health outcomes.

Advanced Multi-Layer Watertight Closure versus Conventional Closure in Total Hip and Knee Replacement Surgery.

Background: In total joint replacement procedures, surgeons have increasingly adopted advanced multi-layer, watertight closure. The objective of the study was to compare the clinical and economic outcomes for advanced multi-layer, watertight closure patients to those with conventional closure with sutures and skin staples. Methods: Patients aged ≥18 years were included in the study if they underwent total joint arthroplasty of the hip or knee as an elective, primary, inpatient procedure between January 2014 and March 2019. Cohorts having advanced multi-layer, watertight closure or conventional closure were compared using multivariable regression analysis of surgical site infections, length of stay, operating room time, procedure time, discharge status, readmissions, reoperations, and hospital emergency department visits. Results: A total of 1828 patients received at least one total hip or knee replacement, of which 434 (23.7%) had advanced multi-layer, watertight closure and 1394 (76.3%) had conventional closure. Unadjusted time to readmission, when occurring, was considerably longer following advanced multi-layer, watertight closure (89.9 vs 51.1 days, p < 0.0001), and a lower proportion of the advanced multi-layer, watertight closure cohort required reoperation within 90 days (0.0% vs 2.6%, p < 0.0001). Adjusted mean hospital length of stay was approximately half of a day shorter for advanced multi-layer, watertight closure patients (1.10 vs 1.65 days; p < 0.001), and they were also more likely to be discharged to home (Odds Ratio: 4.61; p = 0.002). Conclusion: Among patients undergoing total hip and knee arthroplasty in a highly optimized real-world clinical practice, advanced multi-layer, watertight closure was associated with significantly shorter inpatient length of stay and increased likelihood of being discharged to home compared with conventional closure. These findings suggest that advanced multi-layer, watertight closure is a valuable component of an optimal workflow for total hip or knee replacement, and may be especially valuable for high-risk patients.

Use of analgesic, anesthetic, and sedative medications during pediatric hospitalizations in the United States 2008.

BACKGROUND: The wide need for analgesia, anesthesia, and sedation in children and the lack of pediatric labeling leads to widespread off-label use of medications for pain and sedation in children. Any attempt to address the lack of labeling will require national estimates of the numbers of children using each medication, their ages, and other factors, to understand the overall use of these medications. We describe use of analgesics, anesthetics, and sedatives in pediatric inpatients by result of conducting a statistical analysis of medication data from >800,000 pediatric hospitalizations in the United States. The purpose was to provide national estimates for the percentage of hospitalized children receiving specific analgesics, anesthetics, and sedatives and their use by age group. METHODS: Data from the Premier Database, the largest hospital-based, service-level comparative database in the country, were used. We identified all uses of a given medication, selected the first use for each child, and calculated the prevalence of use of specific medications among hospitalized children in 2008 as the number of hospitalizations in which the drug was used per 100 hospitalizations. Dose and number of doses were not considered in these analyses. RESULTS: The dataset contained records for 877,201 hospitalizations of children younger than 18 years of age at the time of admission. Thirty-three medications and an additional 11 combinations were administered in this population, including nonsteroidal antiinflammatory drugs, local and regional anesthetics, opioids, benzodiazepines, sedative-hypnotics, barbiturates, and others. The 10 most frequently administered analgesic, anesthetic, or sedative medications used in this population were acetaminophen (14.7%), lidocaine (11.0%), fentanyl (6.6%), ibuprofen (6.3%), morphine (6.2%), midazolam (4.5%), propofol (4.1%), lidocaine/prilocaine (2.5%), hydrocodone/acetaminophen (2.1%), and acetaminophen/codeine (2.0%). Use changed with age, and the direction of change (increases and decreases) and the type of change (linear, u-shaped, or other) appeared to be specific to each drug. CONCLUSIONS: A variety of drug classes and individual medications were used to manage pain and sedation in hospitalized children. The variation in patterns of use reflects the heterogeneity of the dataset, comprising a wide range of ages and conditions in which analgesia, anesthesia, and sedation might be required. It was not possible to assess whether use of a specific medication was clinically appropriate, except to note use of medications in age subgroups without pediatric labeling.

Ultrasonography guidance reduces complications and costs associated with thoracentesis procedures.

PURPOSE.: We performed an analysis of hospitalizations involving thoracentesis procedures to determine whether the use of ultrasonographic (US) guidance is associated with differences in complications or hospital costs as compared with not using US guidance. METHODS.: We used the Premier hospital database to identify patients with ICD-9 coded thoracentesis in 2008. Use of US guidance was identified using CPT-4 codes. We performed univariate and multivariable analyses of cost data and adjusted for patient demographics, hospital characteristics, patient morbidity severity, and mortality. Logistic regression models were developed for pneumothorax and hemorrhage adverse events, controlling for patient demographics, morbidity severity, mortality, and hospital size. RESULTS.: Of 19,339 thoracentesis procedures, 46% were performed with US guidance. Mean total hospitalization costs were $11,786 (±$10,535) and $12,408 (±$13,157) for patients with and without US guidance, respectively (p < 0.001). Unadjusted risk of pneumothorax or hemorrhage was lower with US guidance (p = 0.019 and 0.078, respectively). Logistic regression analyses demonstrate that US is associated with a 16.3% reduction likelihood of pneumothorax (adjusted odds ratio 0.837, 95% CI: 0.73-0.96; p= 0.014), and 38.7% reduction in likelihood of hemorrhage (adjusted odds ratio 0.613, 95% CI: 0.36-1.04; p = 0.071). CONCLUSIONS.: US-guided thoracentesis is associated with lower total hospital stay costs and lower incidence of pneumothorax and hemorrhage. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound, 2011.

Estimating pediatric inpatient medication use in the United States.

PURPOSE: We demonstrated the feasibility of developing national estimates of pediatric inpatient medication use by analyzing data from a large administrative database. METHODS: Pediatric inpatient data were extracted from Premier Perspective® database to calculate the prevalence of use of specific medications among hospitalized children in 2008. The database was validated by comparing characteristics to the HCUP KID sample of pediatric hospitalizations for 2006. Prevalence was calculated by categorizing patients as ever or never having received a specific drug. RESULTS: The 10 drugs administered in the most pediatric hospitalizations were acetaminophen, lidocaine, ampicillin, gentamicin, fentanyl, ibuprofen, morphine, ondansetron, ceftriaxone, and albuterol. CONCLUSIONS: Although the database is not a probability-based sample, it bears sufficient similarity to a probability-based sample of pediatric hospitalizations (HCUP KID) to serve as a starting point in developing national estimates of inpatient pediatric medication use. Over 500 drug entities were administered to hospitalized children, but most are used by small percentages of hospitalized patients. The small numbers of children using any one drug has implications for efforts to study efficacy and safety, describe off-label use, monitor adverse events, describe practice, and conduct comparative effectiveness research.

Resource utilization and costs associated with chemotherapy-induced nausea and vomiting (CINV) following highly or moderately emetogenic chemotherapy administered in the US outpatient hospital setting.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV), common adverse events of chemotherapy, may be associated with considerable healthcare resource utilization. This study was conducted to describe CINV-associated healthcare visits and costs following a first cycle of highly or moderately emetogenic chemotherapy (HEC or MEC). METHODS: This retrospective cohort study used the Premier Perspective™ Database to identify adult patients who received their first HEC or MEC and at least one antiemetic agent from 2003 to 2007 at US hospital-based outpatient facilities. Hospital visits with a CINV-related ICD-9 diagnosis were included from the chemotherapy administration date to 30 days later or 1 day before the second chemotherapy, whichever was first. CINV costs were hospital-reported costs. RESULTS: Of 19,139 patients (HEC, 16%; MEC, 84%), mean (SD) age was 59 (14) years; 59% were female; 66% were white. CINV prophylaxis included 5-HT3 antagonists (85%), dexamethasone (76%), and NK-1 antagonists (2%). Overall, 13.8% of patients had a CINV-associated visit (HEC, 18%; MEC, 13%): 0.2% for acute CINV (day of chemotherapy, excluding chemotherapy administration visit) and 13.7% for delayed CINV. CINV-associated visits included inpatient (IP, 64%), outpatient (OP, 26%), and emergency room (ER, 10%) visits. Mean (SD) costs of CINV visits were $5,299 ($6,639); for IP, $7,448 ($7,271); OP, $1,494 ($2,172); and ER, $918 ($1,071). Mean per-patient CINV-associated costs across all patients were $731 ($3,069). Sensitivity analysis excluding visits where CINV was a secondary diagnosis code resulted in a CINV incidence of 4.4%, a mean CINV visit cost of $4,043, and a mean per-patient CINV-associated cost across all patients of $176. CONCLUSIONS: CINV visits in the first HEC or MEC cycle were common and costly, especially inpatient hospitalizations in the delayed phase. Strategies to reduce CINV in the delayed phase could reduce healthcare utilization and costs.

Integrated clinical pathways with watertight, multi-layer closure to improve patient outcomes in total hip and knee joint arthroplasty.

The number of primary total hip and knee replacement surgeries is increasing primarily due to an aging population. There is also a concomitant increase in the number of complications which could be attributed to high variation in arthroplasty techniques, peri-operative methods and the absence of integrated clinical pathways (ICP) to mitigate risks such as surgical site infections (SSIs). The implementation of ICPs incorporating watertight, multi-layer closure could increase the preventative effectiveness against joint prosthetic adverse events. The objective of this review is to describe the ICPs implemented by one US facility to help address ten adverse events synergistically.

Budget Impact of a Steroid-Eluting Sinus Implant Versus Sinus Surgery for Adult Chronic Sinusitis Patients with Nasal Polyps.

BACKGROUND: A corticosteroid-eluting sinus implant was recently approved by the FDA as a drug to treat adult patients with nasal polyps who have undergone previous endoscopic sinus surgery (ESS) of the ethmoid sinuses. ESS is performed in an operating room under general anesthesia, whereby diseased tissue and bone are removed to provide improved drainage. ESS typically involves dissection of 1 or more of the 4 paired sinus cavities (maxillary, ethmoid, sphenoid, or frontal). The implant, containing 1,350 mcg of mometasone furoate, is inserted by a physician in an office setting and offers controlled localized release of corticosteroid to the polypoid sinus tissue. The implant has demonstrated significant improvements in clinical testing; however, little research has been conducted on its economic impact. OBJECTIVE: To evaluate and quantify the budget impact to a commercial payer of using this implant instead of ESS in patients with nasal polyps after a previous ESS. Since essentially all patients with recurrent nasal polyps after ESS are patients with chronic sinusitis (CS) diagnosis, this study also identified patients with CS with nasal polyposis (CSwNP) for consistency with the patient population studied in clinical trials evaluating the implant. METHODS: A budget impact analysis was conducted from a U.S. commercial payer perspective over a 1-year time horizon with patients who received the implant or revision ESS. Primary outcomes of interest were annual total and per-member per-month (PMPM) direct health care costs. Costs were estimated using a decision analysis model, assuming 50% implant utilization as an alternative to revision ESS in eligible patients, with other levels (25%, 75%) also considered. The model utilized the results of a recently published analysis of 86,052 patients in the Blue Health Intelligence database, results from published clinical trials evaluating the implant, a literature review, and published Medicare national payment amounts. RESULTS: A commercial health plan with 1 million members could anticipate 1,000 CSwNP patients as candidates for receiving the implant or revision ESS. Estimated direct treatment costs for refractory CSwNP using only revision ESS are $11.03 million ($0.92 PMPM). If the implant replaced surgery in 50% of cases and if 63% those patients received a second treatment with the implant during the year, the estimated total cost savings would be $2.56 million ($0.21 PMPM). Cost savings associated with using the implant changed to $0.11 PMPM and $0.32 PMPM with implant adoption of 25% and 75%, respectively. CONCLUSIONS: In a large commercially insured U.S. population, annual revision ESS costs are substantial. Using the implant instead of revision ESS could result in considerable cost savings for payers at various levels of adoption. DISCLOSURES: This study was sponsored by Intersect ENT, which was involved in study design and manuscript review. Ernst and Imhoff are employed by CTI Clinical Trial and Consulting Services, which contracted with Intersect ENT to conduct this study. Ernst and Imhoff also report other financial support from Intersect ENT during the conduct of the study. DeConde reports personal fees from Intersect ENT during the conduct of the study, as well as personal fees from Optinose, Stryker Endoscopy, and Olympus, outside the submitted work. Manes reports grants from Intersect ENT during the conduct of the study, as well as grants from Optinose and Sanofi outside the submitted work.

Health Economics and Outcomes of Surfactant Treatments for Respiratory Distress Syndrome Among Preterm Infants in US Level III/IV Neonatal Intensive Care Units.

OBJECTIVE: To compare length of stay (LOS), costs, mechanical ventilation (MV), and mortality in preterm infants treated in the Neonatal Intensive Care Unit (NICU) with beractant (BE), calfactant (CA), and poractant alfa (PA) for Respiratory Distress Syndrome (RDS). METHODS: This study evaluated preterm infants born between 2010 and 2013 with RDS diagnosis, gestational age of 25 to 36 weeks, birthweight of ≥500 g, and age of ≤2 days on first surfactant administration. Multivariable regression was used to evaluate all NICU outcomes. RESULTS: Of 13,240 infants meeting the study criteria, 4136 (31.2%) received BE, 2502 (18.9%) received CA, and 6602 (49.9%) received PA. Adjusted analyses estimated similar mean LOS (BE 26.7 days, CA 27.8 days, and PA 26.2 days) and hospital costs (BE: $50,929; CA: $50,785; and PA: $50,212). Compared to PA, BE and CA were associated with greater odds of MV use on day 3 (OR = 1.56 and 1.60, respectively) and day 7 (OR = 1.39 and 1.28, respectively; all p < 0.05). Adjusted NICU mortality was significantly higher only with CA vs PA (OR = 1.51; p = 0.015). CONCLUSION: Adjusted NICU LOS and costs were similar among BE, CA, and PA. Infants receiving PA were less likely to be on MV at 3 and 7 days, and PA treatment was associated with lower odds of NICU mortality when compared to CA.

The 3-year clinical and functional course of schizophrenia among individuals with and without diabetes at study entry.

OBJECTIVE: This prospective observational study compared the 3-year clinical and functional course of schizophrenia among individuals with and without diabetes at study entry. METHOD: Data were drawn from a large, 3-year, multisite, prospective, naturalistic study of treatment for schizophrenia-related disorders. The study was conducted in the United States between July 1997 and September 2003 and represented treatment practices in diverse systems of care. Participants were diagnosed with schizophrenia or schizoaffective or schizophreniform disorders based on DSM-IV criteria. Clinical and functional outcomes were assessed at study enrollment and at 12-month intervals using standard psychiatric measures, medical records, and a validated patient-reported questionnaire. Diabetes status was determined by participant interview at enrollment. Statistical analyses used mixed models with repeated measures. RESULTS: Of 594 participants queried about comorbid medical conditions at enrollment, 76 (12.8%) reported having diabetes. Other comor-bid conditions were reported by 79% of the diabetes group (N = 60) and 50% of the nondiabetes group (N = 259). Across the 3-year study, participants with diabetes differed significantly from participants without diabetes on 2 of 36 outcome measures: more contacts with nonpsychiatrist physicians (p < .001) and poorer physical health (p = .015). Groups did not differ significantly on mental health symptomatology, mental health resource utilization, legal and safety issues, substance use, productivity, activities and relationships, or quality of life. CONCLUSIONS: In this 3-year, prospective, naturalistic study, the course of schizophrenia did not differ significantly between participants with and without diabetes, although persons with diabetes did have poorer physical health and more contacts with nonpsychiatrist physicians. Findings highlight the need for better medical treatment for people with schizophrenia, both with and without comorbid diabetes.

Relapse outcomes, safety, and treatment patterns in patients diagnosed with relapsing-remitting multiple sclerosis and initiated on subcutaneous interferon ß-1a or dimethyl fumarate: a real-world study.

OBJECTIVE: To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) ß-1a (Rebif) vs dimethyl fumarate (DMF; Tecfidera), to treat relapsing-remitting multiple sclerosis (RRMS). METHODS: A US retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN ß-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN ß-1a or DMF, or (b) previously treated, switching to sc IFN ß-1a or DMF. Two years' follow-up data were captured. Patient characteristics, persistence, and adverse events between treatment groups were compared using t-tests or Chi-square tests. Kaplan-Meier curves with log-rank tests and Cox proportional hazards models were used to compare time to, and risk of non-persistence. Annualized Relapse Rates (ARR) were calculated using a robust variance Poisson model adjusting for covariates. Propensity scores were used to address possible selection bias. RESULTS: One hundred and twelve patients became non-persistent, most commonly due to an adverse event (n = 37). No difference was observed in time to overall non-persistence between sc IFN ß-1a and DMF patients. Among treatment-naïve patients, those receiving DMF had 2.4-times the risk (HR = 2.439, 95% CI = 1.007-5.917, p = .0483) of experiencing a discontinuation than patients receiving sc IFN ß-1a. Non-persistent patients receiving DMF had 2.3-times the risk (HR = 2.311, 95% CI = 1.350-3.958, p = .0023) of experiencing an adverse event at a given time point than patients prescribed sc IFN ß-1a. No differences in relapse risk or ARR between sc IFN ß-1a- and DMF-treated patients were observed. CONCLUSIONS: sc IFN ß-1a-treated patients had comparable persistence and relapse outcomes, and better safety outcomes vs DMF-treated patients across 2 years.

Retrospective Study of Patients Switched from Tablet Formulations to a Gel Cap Formulation of Levothyroxine: Results of the CONTROL Switch Study.

INTRODUCTION: Medication changes involving levothyroxine-either dose titrations or switching formulations-occur frequently in patients with erratic thyroid-stimulating hormone (TSH) levels and persistent hypothyroid symptoms. We investigated whether switching patients from levothyroxine tablets to a gel cap formulation of levothyroxine might reduce dose adjustments and improve tolerability and efficacy outcomes. OBJECTIVES: Primary study objectives included quantifying the percentage of patients achieving TSH levels within a pre-specified range, median dose changes experienced, and the percentage of patients with improved hypothyroid symptom control after switching from levothyroxine tablets to levothyroxine gel caps. METHODS: A retrospective medical chart review was conducted among 99 randomly selected hypothyroid patients who were switched from a tablet to a gel cap formulation of levothyroxine. Patients were required to have been on levothyroxine monotherapy for ≥1 year prior to the medication switch. Data was collected for 6 months pre-switch and up to 6 months post-switch. RESULTS: Of the 99 patients studied, the majority (51.5%) experienced no documented change in TSH status after the switch (P < 0.0001). However, there was a decrease in the mean number of dose changes experienced (1.61 ± 0.96 vs. 0.73 ± 0.96; P < 0.0001). Improved hypothyroid symptom control was reported among 61.6% of patients (61 of 99; P < 0.0001). CONCLUSION: The results of CONTROL Switch support a strategy of switching patients who may experience tolerability or efficacy problems with standard levothyroxine tablets to the levothyroxine gel cap formulation.

The Economic Impact of Levothyroxine Dose Adjustments: the CONTROL HE Study.

BACKGROUND: In general, hypothyroidism can be adequately treated with a consistent daily dose of levothyroxine. However, the need for levothyroxine dose adjustments is frequent in clinical practice. The extent to which levothyroxine dose adjustments increase the utilization of healthcare resources has not previously been described in the clinical literature. OBJECTIVE: The primary objective of our study was to measure the effect of levothyroxine dose adjustments in terms of their utilization of healthcare resources including direct and indirect costs. A secondary goal was to identify any differences in patient characteristics that may be responsible for levothyroxine dose adjustments. METHODS: A retrospective medical chart review was conducted among patients of selected healthcare providers in the USA. Patients who were recently started on levothyroxine therapy (<6 months) were excluded to avoid situations that were more likely attributable to treatment initiation than inadequate therapeutic effect. Trained nurses extracted data from patient charts and electronic medical record systems for review. We analyzed the cost of resources consumed by the frequency of levothyroxine dose changes over 24 months: 0 dose changes (no dose adjustment group); one dose change, two dose changes, three or more dose changes (≥1 dose adjustment group). RESULTS: The study included 454 patients. Overall estimated resource utilization was higher per patient in the ≥1 dose adjustment group (US$5824) vs. the no dose adjustment group (US$3166) during the 24-month study period. When direct and indirect costs were combined, overall costs of care were greatest in patients requiring three or more dose adjustments (US$8220/patient). Patients in this cohort incurred 2.5-fold greater total costs compared with patients requiring no dose adjustments (US$8220 vs. US$3166). Among the 58 patients in the group requiring three or more dose adjustments, mean direct medical costs were significantly higher than in the patients requiring no dose adjustments (US$6387 vs. US$2182). Patients with at least one dose adjustment experienced a 40.3% increase in lost productivity vs. patients who had no dose adjustments (US$1381 vs. US$984). Loss of productivity was highest among patients with three or more levothyroxine dose adjustments. Among this cohort, there was an 86.4% increase in lost productivity vs. patients who had no levothyroxine dose adjustments (US$1833 vs. US$984). CONCLUSIONS: Patients experiencing multiple levothyroxine dose adjustments were shown to consume more healthcare resources, resulting in higher costs than those who required no dose adjustments. Each care episode contributed to lost time and wages with total estimated lost productivity escalating with increasing levothyroxine dose adjustments over a 24-month period.

Medication adherence and long-term functional outcomes in the treatment of schizophrenia in usual care.

BACKGROUND: Relatively little is known about the relationships between medication adherence and long-term functional outcomes in the treatment of schizophrenia. To extend previous research, we prospectively examined the relationships between adherence with any antipsychotic medication and functional outcomes among schizophrenia patients treated over a 3-year period, assessed the stability of adherence over time, and examined whether adherence in the first year predicts changes in functional outcomes over the following 2 years. METHOD: Analyses included 1906 participants with DSM-IV diagnoses of schizophrenia or schizoaffective or schizophreniform disorder in a multi-site, 3-year, prospective, naturalistic study conducted in the United States between July 1997 and September 2003. Outcome measures were assessed at 6-month intervals using systematic medical record abstraction and structured interview of patients. Adherence with antipsychotic regimen was assessed using patient-reported adherence and the medication possession ratio (percent days with prescription for any antipsychotic), dichotomized into adherence and non-adherence. Analyses employed generalized estimating equations and mixed models with repeated measures. RESULTS: Nonadherence was associated with poorer functional outcomes, including greater risks of psychiatric hospitalizations, use of emergency psychiatric services, arrests, violence, victimizations, poorer mental functioning, poorer life satisfaction, greater substance use, and more alcohol-related problems (all p < .001). Adherence was relatively stable, with 77.3% of patients maintaining the same adherence status from the first year to the second year. Nonadherence in the first year predicted significantly poorer outcomes in the following 2 years. CONCLUSIONS: Findings highlight the importance of adherence with antipsychotic medication in the long-term treatment of schizophrenia and its potential beneficial impact on the mental health and criminal justice delivery systems.

Use of drotrecogin alfa (activated) in older patients with severe sepsis.

Drotrecogin alfa (activated) has been approved by the United States Food and Drug Administration for treatment of patients at high risk of death from severe sepsis. Severe sepsis is common, and its occurrence increases dramatically with age. Clinical use data, however, suggest that drotrecogin alfa (activated) may be underused in older patients, possibly due to concern over the drug's anticoagulant effects and perceived high cost. In addition, clinicians often treat older patients less aggressively than younger patients. We reviewed a subgroup analysis of patients aged 75 years and older from a large clinical trial evaluating efficacy and safety of drotrecogin alfa (activated), as well as cost-effectiveness data from real-world clinical use of the drug in older patients. We also explored ethical dilemmas of treating older patients with sepsis. Drotrecogin alfa (activated) is safe, effective, and cost-effective in older patients with severe sepsis and should be considered for elderly intensive care patients who are high risk of death and who have no contraindications to treatment.

Analysis of Diagnoses Associated with Multiple Sclerosis-Related In-Hospital Mortality Using the Premier Hospital Database.

BACKGROUND: We sought to compare mortality rates and related diagnoses in hospitalized patients with multiple sclerosis (MS), those with diabetes mellitus (DM), and the general hospitalized population (GHP). METHODS: Patients who died between 2007 and 2011 were identified in the US hospital-based Premier Healthcare Database. Demographic information was collected, mortality rates calculated, and principal diagnoses categorized. RESULTS: Of 55,152 unique patients with MS identified, 1518 died. Mean age at death was 10 years younger for the MS group (63.4 years) than for the DM (73.3 years) and GHP (73.1 years) groups. Age-adjusted mortality rates, based on the 2000 US Standard Million Population, were 1077, 1248, and 1133 per 100,000, respectively. Infection was the most common principal diagnosis at the hospital stay during which the patient died in the MS cohort (43.1% vs. 26.3% and 24.0% in the DM and GHP groups, respectively). Other common principal diagnoses in the MS group included pulmonary (17.5%) and cardiovascular (12.1%) disease. Septicemia/sepsis/septic shock was a secondary diagnosis for 50.7% of patients with MS versus 36.0% and 31.0% of patients in the DM and GHP cohorts, respectively. CONCLUSIONS: Patients with MS had a shorter life span than patients with DM or the GHP and were more likely to have a principal diagnosis of infection at their final hospital stay. However, the database was limited to codes recorded in the hospital; diagnoses received outside the hospital were not captured.

Value of Propensity Score Matching for Equalizing Comparator Groups in Observational Database Studies: A Case Study in Anti-infectives.

PURPOSE: Propensity score methodologies can reduce bias and confounding in nonrandomized studies, including pharmaceutical comparative effectiveness studies. An observational case study was developed to demonstrate the impact of propensity score adjustments on outcomes (ie, discharge status) of patients hospitalized for complicated intra-abdominal infections. METHODS: Two cohorts were examined: intensive care unit (ICU) (vs non-ICU) patients and tigecycline-treated patients (vs patients receiving other antibiotics). Discharge status was captured before propensity scoring. FINDINGS: The impact of propensity scoring on discharge outcome was greater when comparing ICU patients versus non-ICU patients than when comparing tigecycline recipients versus nonrecipients. IMPLICATIONS: Propensity scoring should be examined carefully to optimize its effects. Moreover, propensity scoring only addresses bias and confounding in nonrandomized studies that are attributable to variables contained within the dataset (ie, so called "observables") and not to other variables that may influence the relationship between outcomes and other independent variables.

Comparative resource utilization and costs for patients with acute coronary syndrome managed with percutaneous coronary intervention and treated with clopidogrel or prasugrel.

PURPOSE: Results of a study of bleeding events and other inhospital outcomes with the use of clopidogrel versus prasugrel in patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) are reported. METHODS: Demographic and clinical data on adults hospitalized for ACS, managed with PCI, and treated with clopidogrel or prasugrel during a two-year period were extracted from a large hospital claims database. Bleeding rates, hospital length of stay (LOS), and total hospital costs during the index hospitalization were evaluated. RESULTS: The study sample consisted of 75,297 patients who received clopidogrel and 9,477 who received prasugrel. The unadjusted bleeding rates were 5.7% with clopidogrel use and 3.2% with prasugrel use (p < 0.0001). After propensity score stratification to adjust for selection bias, rates of bleeding events were not significantly different between clopidogrel- and prasugrel-treated patients (odds ratio, 0.90; 95% confidence interval [CI], 0.80-1.02; p = 0.0949). The adjusted mean ± S.D. hospital LOS was 0.22 day lower (95% CI, 0.15-0.28; p < 0.001) with the use of prasugrel versus clopidogrel, and adjusted total mean hospital costs were $375 less for prasugrel-treated patients (p = 0.003). CONCLUSION: After adjustments for demographic and clinical characteristics, rates of inhospital bleeding in patients who received prasugrel and those who received clopidogrel were not significantly different. The adjusted analyses showed that the mean hospital LOS was shorter and total mean hospital costs were lower for patients treated with prasugrel.

Treatment for Multiple Acute Cardiopulmonary Conditions in Older Adults Hospitalized with Pneumonia, Chronic Obstructive Pulmonary Disease, or Heart Failure.

OBJECTIVES: To determine how often hospitalized older adults principally diagnosed with pneumonia, chronic obstructive pulmonary disease (COPD), or heart failure (HF) are concurrently treated for two or more of these acute cardiopulmonary conditions. DESIGN: Retrospective cohort study. SETTING: 368 U.S. hospitals in the Premier research database. PARTICIPANTS: Individuals aged 65 and older principally hospitalized with pneumonia, COPD, or HF in 2009 or 2010. MEASUREMENTS: Proportion of diagnosed episodes of pneumonia, COPD, or HF concurrently treated for two or more of these acute cardiopulmonary conditions during the first 2 hospital days. RESULTS: Of 91,709 diagnosed pneumonia hospitalizations, 32% received treatment for two or more acute cardiopulmonary conditions (18% for HF, 18% for COPD, 4% for both). Of 41,052 diagnosed COPD hospitalizations, 19% received treatment for two or more acute cardiopulmonary conditions (all of which involved additional HF treatment). Of 118,061 diagnosed HF hospitalizations, 38% received treatment for two or more acute cardiopulmonary conditions (34% for pneumonia, 9% for COPD, 5% for both). CONCLUSION: Hospitalized older adults diagnosed with pneumonia, COPD, or HF are frequently treated for two or more acute cardiopulmonary conditions, suggesting that clinical syndromes often fall between traditional diagnostic categories. Research is needed to evaluate the risks and benefits of real-world treatment for the many older adults whose presentations elicit diagnostic uncertainty or concern about coexisting acute conditions.