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Background While CRE and DAT are both associated with worse outcomes, their relative impact to the clinical and economic burden among patients with infections due to Enterobacteriaceae is not well understood. This study assessed the independent and combined effect of these two items on selected outcomes among patients with these infections. Methods Hospitalized adults between July 2011 and September 2014 were identified from Premier Hospital Database. Patients were diagnosed with complicated urinary tract infection, complicated intra-abdominal infection, hospital-associated pneumonia, or bloodstream infection, and had a positive culture for Enterobacteriaceae from a site consistent with infection type (date of culture draw was index date). Patients were required to receive antibiotics on this date or ≤2 days after. Delayed therapy was defined as no receipt of an antibiotic with microbiologic activity during this period. CRE was defined as resistant to ≥1 carbapenems. Inverse probability weighting and multivariate regression analyses were used to estimate the associations between CRE status, DAT and outcomes. Logistic models were used for composite mortality (in-hospital death or discharge to hospice), in-hospital mortality, and discharge to home (reference group was timely therapy plus non-CRE); generalized linear models, for post-index duration of antibiotic therapy, hospital length of stay (LOS), and costs. Results A total of 50,069 patients were included in the analyses; 514 had CRE and 16,414 received DAT. A gradient effect was observed across strata as the burden of serious infections was least among the reference group, and greatest among patients with CRE infection who received DAT (Figure). For example, as compared with the reference group, the risk of composite mortality increased nearly fourfold in patients with CRE infection who received DAT; total in-hospital costs more than doubled. Conclusion DAT has a stronger association than CRE on outcomes, and their effects are synergistic. Given these findings, better methods of early pathogen identification (especially organisms such as CRE) should reduce time to appropriate therapy, thereby improving outcomes in this patient population. Disclosures T. Lodise, Allergan plc: Consultant, Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium; A. Berger, Allergan plc: Consultant, Consulting fee; A. Altincatal, Evidera: Consultant, Salary; R. Wang, Evidera: Employee, Salary; T. Bhagnani, Allergan plc: Consultant, Consulting fee; P. Gillard, Allergan plc: Employee, Salary; N. G. Bonine, Allergan plc: Employee, Salary

The incidence and consequences of post-operative infections in patients undergoing major elective surgery is not well understood.Using a large U.S. healthcare claims database, we identified all patients who underwent major elective surgery between January 1, 2007, and December 31, 2009. For each such patient, date of the first-noted surgery during this period was designated as the index date. Patients who developed infections within 30 d of their index date were matched to those who did not using propensity score matching. We compared hospital readmissions, mortality, and total healthcare cost during the 30-d period following index date between patients who developed post-operative infections versus those who did not.A total of 327,618 patients met all selection criteria. At 30 d following major elective surgery, 10.9% of patients had evidence of post-operative infections, 39% of which occurred during the index admission. In propensity-matched analyses, patients with post-operative infections were about five times as likely to be readmitted to hospital (11.3% vs. 2.1%) and more than twice as likely to die (0.8% vs. 0.3%) in the 30-d period following surgery; their average total healthcare cost was $8,417 higher ($29,229 vs. $20,812) (all comparisons, p0.01).Approximately one in 10 patients undergoing major elective surgery develop post-operative infections by day 30. Post-operative infections are associated with significantly worse clinical outcomes and higher total healthcare cost.

Consequences of initial antibiotic failure in patients hospitalized for complicated skin and skin-structure infections (cSSSI) are not well understood.Using data from100 hospitals in the United States, we identified all adults hospitalized for cSSSI between January 1, 2000 and June 30, 2009. We defined "initial therapy" as all parenteral antibiotics administered24 h of admission, and such therapy was assumed to have failed if the patient (1) received new antibiotic(s) subsequently (excluding similar/narrower spectrum antibiotics or those begun at discharge), or (2) underwent drainage/debridement/amputation72 h after admission. We limited attention to the 40 most commonly used antibiotic regimens in 2009. We compared clinical and economic outcomes of patients who experienced initial treatment failure and those who did not.The rate of initial treatment failure was 16.6% in acute infections (n=13,498), 34.1% in chronic/ulcerative infections (n=1,116), and 26.7% in surgical site infections (SSIs) (n=2,929). Treatment failure was associated with 4.1-7.3 additional days in the hospital and $11,995-$23,655 in additional inpatient charges; the case fatality rate was from 4- to 12-fold higher in patients who experienced treatment failure than in those who did not (all comparisons, p0.01).Initial treatment failure in patients hospitalized for cSSSI is associated with significantly worse clinical outcomes, longer hospital stays, and higher hospital charges than with successful initial treatment.

To identify risk factors for initial treatment failure in patients with community-acquired pneumonia (CAP) in non-intensive care unit (non-ICU) settings, and to characterize the association between initial treatment failure and length of stay, total hospital charges, and mortality.Retrospective cohort study. Using data from100 US hospitals, this study identified all adults (age ≥18 years) hospitalized for pneumonia between January 1, 2000 and June 30, 2009 who began antibiotic therapy within 24 h of admission and were treated for at least 48 h if alive; patients admitted to intensive care within the first 24 h in hospital were excluded. Initial therapy was defined as all parenteral antibiotics administered within the first 24 h in hospital. Treatment failure was assessed based on subsequent receipt of new antibiotic(s), excluding agents of similar/narrower spectrum and those begun at discharge. Multivariate logistic regression was used to identify risk factors for treatment failure, and multivariate linear and logistic regression to compare length of stay, total hospital charges, and in-hospital mortality between patients experiencing initial treatment failure and those who did not.Among 32,324 patients with non-ICU CAP, 4695 (14.6%) experienced initial treatment failure, most often within 72 h of hospital admission. Significant predictors of initial treatment failure included malnourishment (OR = 1.87; 95% CI = 1.60-2.18), receipt of vasoactive medications within 24 h of admission (1.51 [1.17-1.94]), and renal failure (1.45 [1.32-1.59]). Treatment failure was associated with higher case fatality (8.5% vs 3.3%), longer hospital stays (mean [SD] = 10.1 [8.1] days vs 4.9 [3.3] days), and higher total hospital charges ($37,602 [$71,876] vs $14,371 [$21,633]) (all comparisons, p0.01). Study limitations include possible inclusion of patients with healthcare-associated pneumonia (HCAP) in the study sample, our focus on the 40 most commonly used antibiotic regimens, and indirect measurement of treatment failure.Approximately one in seven non-ICU CAP patients experience failure of initial antibiotic therapy. Risk of failure is higher for patients with significant comorbidities and/or severe infections. Non-ICU patients who experience initial treatment failure have significantly longer hospital stays, higher total hospital charges, and higher rates of mortality.

Background: Allogeneic HCT is a potentially curative procedure for many hematologic malignancies, but is associated with several complications. Acute GvHD is a condition that affects 35-50% of allogeneic HCT recipients, typically occurs within 100 days after transplant, and can be life-threatening. Existing treatments are poorly tolerated and frequently ineffective. While the clinical consequences of acute GvHD are understood, the economic burden of the condition has not been well characterized. Methods: Using a large US healthcare claims database (Truven MarketScan® Commercial Claims and Encounters Database), patients aged ≥2 years old were identified who underwent allogeneic HCT between October 2009 and March 2013. Patients without continuous health plan enrollment or evidence of hematologic malignancy in the 6-month period prior to the "Index Admission" (hospital admission during which HCT was performed) were excluded. Patients were followed from the first day of the Index Admission until death, plan disenrollment, or one year; whichever occurred first ("Follow-Up"). Patients were classified into two cohorts: "Acute GvHD" based on ICD-9 CM diagnosis codes within first 100 days of Follow Up, or "No Acute GvHD". Total healthcare costs (inpatient care, outpatient care, outpatient pharmacy) and hospital length of stay (LOS) at discharge from Index Admission, the 100th day of Follow-Up, and the 365th day of Follow-Up were determined. Reimbursed amounts (plan payment plus patient liability) were used as a proxy for healthcare costs. Total healthcare costs and LOS between the two cohorts were compared for each of the three evaluation periods using Student's t-tests (unadjusted analyses), and analyses of covariance (ANCOVA; adjusting for differences in age, sex, plan type, geography, year of Index Admission, type of malignancy, Charlson Comorbidity Index score, and pre-admission healthcare cost). Results: 1,635 patients underwent HCT and met all selection criteria (mean age was 48 years, 56% were men, acute myeloid leukemia was the most common malignancy); 42% met the criteria for inclusion in the Acute GvHD cohort. Univariate mean total healthcare costs for the Acute GvHD cohort (vs No Acute GvHD) were $36,651 greater during Index Admission, $83,322 greater at the 100th day of Follow-Up, and $123,220 greater at the end of the 1-year Follow-Up (all p Conclusions: Over the one-year period following allogeneic HCT, patients who develop Acute GvHD experience over $100,000 more in total healthcare costs-and nearly three additional weeks in hospital-relative to those who do not. While healthcare claims appear to represent a good source with which to assess the impact of complications of HCT, confirmation with prospective clinical studies is recommended. Given that nearly one-half of patients develop Acute GvHD, our findings suggest that therapeutic strategies that prevent this complication may confer substantial savings to the healthcare system. Disclosures Grubb: Fate Therapeutics: Employment, Equity Ownership. Huse:Evidera: Employment; Fate Therapeutics: Consultancy. Alam:Evidera: Employment; Fate Therapeutics: Consultancy. Dychter:Fate Therapeutics: Employment, Equity Ownership. Wingard:Merck: Consultancy; Ansun: Consultancy; Fate Therapeutics: Consultancy; Gilead: Consultancy; Astellas: Consultancy. Berger:Evidera: Employment; Fate Therapeutics: Consultancy.

Background Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and benzodiazepine anxiolytics are used in the US to treat generalized anxiety disorder (GAD). While benzodiazepines typically provide rapid symptomatic relief, long-term use is not recommended due to risks of dependency, sedation, falls, and accidents. Methods Using a US health insurance database, we identified all persons with GAD (ICD-9-CM diagnosis code 300.02) who began a long-term course of treatment (≥90 days) with a benzodiazepine anxiolytic between 1/1/2003 and 12/31/2007, We compared healthcare utilization and costs over the six-month periods preceding and following the date of treatment initiation (“pretreatment” and “post-treatment”, respectively), and focused attention on accident-related encounters (e.g., for treatment of fractures) and care received for other reasons possibly related benzodiazepine use (e.g., sedation, dizziness). Results A total of 866 patients met all study entry criteria; 25% of patients began treatment on an add-on basis (i.e., adjunctive to escitalopram, paroxetine, sertraline, or venlafaxine), while 75% of patients did not receive concomitant therapy. Mean total healthcare costs increased by $2334 between the pretreatment and post-treatment periods (from $4637 [SD=$9840] to $6971 [$17,002]; p Conclusions Healthcare costs increase in patients with GAD beginning long-term (≥90 days) treatment with a benzodiazepine anxiolytic; a substantial proportion of this increase is attributable to care associated with accidents and other known sequelae of long-term benzodiazepine use.

Background Clinical characteristics and patterns of healthcare utilization in patients with painful neuropathic disorders (PNDs) who are under the care of general practitioners (GPs) in the UK are not well understood. Methods Using a large electronic UK database, we identified all adults (age ≥ 18 years) with any GP encounters between 1 January 2006 - 31 December 2006 at which a diagnosis of PND was noted ("PND patients"). An age-and gender-matched comparison group also was constituted consisting of randomly selected patients with one or more GP encounters-but no mention of PNDs-during this period. Characteristics and patterns of healthcare utilization of patients in the two groups were then examined over the one-year study period. Results The study sample consisted of 31,688 patients with mention of PNDs and an equal number of matched comparators; mean age was 56 years, and 62% were women. The prevalence of various comorbidities was higher among patients in the PND group, including digestive disorders (31% vs. 17% for comparison group), circulatory disorders (29% vs. 22%), and depression (4% vs. 3%) (all p < 0.01). Receipt of prescriptions for pain-related pharmacotherapy also was higher among PND patients, including nonsteroidal anti-inflammatory drugs (56% of PND patients had one or more such prescriptions vs. only 22% in the comparison group), opioids (49% vs. 12%), tricyclic antidepressants (20% vs. 1%), and antiepileptics (12% vs. 1%) (all p < 0.01). PND patients also averaged significantly more GP visits (22.8 vs. 14.2) and referrals to specialists (2.8 vs. 1.4) over one year (both comparisons p < 0.01). Conclusions Patients with PNDs under the care of GPs in the UK have relatively high levels of use of healthcare services and pain-related pharmacotherapy.

Background In 2005, the mean weekly dose ratio of epoetin alfa (EA) to darbepoetin alfa (DA) in clinical practice was estimated to be ∼400 to 1. In 2006, a 500-μg dose and new dosing schedule was approved for DA in the United States. In 2007, the warnings and dosing/administration sections were modified for both agents. All of these factors may have changed the way that physicians use EA and DA. Previous studies of the use of erythropoiesis-stimulating agents (ESAs) in patients with anemia concomitant with chemotherapy may thus not reflect current clinical practice. Objective The goal of this study was to examine the use and costs of ESAs in clinical practice in patients with anemia concomitant with chemotherapy. Methods Using 2 large US health care claims databases, all adults (aged ≥18 years) were identified who received ESAs in 2008 and had evidence of receipt of chemotherapy ≤42 days before initial ESA receipt (ie, the index date). Episodes of care were defined as beginning on the index date and ending on the date of the last ESA claim that was followed by a ≥42-day gap without any receipt of ESAs, to which was added an assumed duration of clinical benefit (in days) based on the ESA and corresponding dose received. DA- and EA-treated patients were matched using propensity scoring. The mean weekly dose and cost of DA and EA during episodes of care was calculated using all information from relevant claims noted during such episodes. Each database was analyzed separately. Results In the first database, 475 patients with DA episodes of care were matched to an equal number of patients with EA episodes; in the second database, there were 424 matched pairs. In the first database, the mean (95% CI) weekly dose was 37,444 U (35,942 U–39,001 U) during EA episodes and 110 μg (108 μg–113 μg) during DA episodes; the mean weekly EA/DA dose ratio was 340 to 1. In the second database, the mean (95% CI) weekly dose was 37,047 U (35,944 U–38,175 U) during EA episodes and 121 μg (117 μg–125 μg) during DA episodes; the mean weekly EA/DA dose ratio was 306 to 1. Conclusions The mean weekly EA/DA dose ratio during episodes of ESA care has declined in patients with anemia concomitant with chemotherapy, due at least in part to the availability and use of a new dose/dosing schedule for DA without similar changes for EA.

Invasive meningococcal disease (IMD) is under-reported in countries that do not employ polymerase-chain reaction for surveillance because culture-negative cases are omitted. To evaluate a clinically based, case-finding method, we developed case definitions for "probable," "compatible with," and "possible, but unlikely" IMD, respectively, based on supportive documentation (e.g., discharge diagnosis of meningococcal infection, culture-negative bacterial meningitis, petechiae/purpura, Gram-negative diplococci on Gram stain) and weight of clinical evidence, which we then applied to electronic health records for all children aged ≤5 y who were admitted to approximately 100 US hospitals between January 2000 and June 2009. Among 47,863 qualifying admissions, 16 children had culture-positive IMD, 5 had "probable" IMD, and 5 had illness "compatible with" IMD. Five additional children had disease considered "possible but unlikely" IMD. Our case-finding methods suggest that culture-based ascertainment may underestimate the number of IMD cases by 31-63%, supporting findings in other nations that culture-based reporting provides incomplete information on disease incidence and therefore underestimates the potential benefits of routine vaccination of young children against meningococcal disease.

To characterize adherence with antidepressants, antiepileptic drugs, and beta blockers as prophylaxis against migraine in typical clinical practice.Using a large US health insurance claims database (calendar years 2003 to 2005), we identified all patients with migraine who began prophylaxis with selected antidepressants, antiepileptic drugs, or beta blockers ("study agents"). Patients not continuously enrolled for 6 months prior to start of prophylaxis ("pretreatment") and for 6 months subsequently ("follow-up") were excluded. Treatment cohorts were constituted based on the type of prophylaxis received. Adherence with migraine prophylaxis was examined by type of agent received using medication possession ratios (MPRs), defined as total days with medication divided by total follow-up days. MPR0.80 was considered indicative of nonadherence.A total of 4,634 patients met all entry criteria and received antidepressants (n = 1,803), antiepileptics (n = 1,896), or beta blockers (n = 935) on their index date. Over the next 6 months, the mean (SD) number of prescriptions for study agents was 2.7 (1.9) for antidepressants, 2.9 (2.0) for antiepileptics, and 2.8 (2.0) for beta blockers, totaling 91.0 (71.4), 98.7 (75.6), and 96.7 (73.0) therapy-days, respectively. Mean MPR at 6 months was 0.48 for antidepressants, 0.51 for antiepileptics, and 0.51 for beta blockers. By the end of the follow-up, 73.4%, 70.2%, and 67.6% of patients who initiated migraine prophylaxis with antidepressants, antiepileptics, and beta blockers, respectively, were designated nonadherent (ie, MPR0.80).Our findings suggest that many patients who begin migraine prophylaxis with antidepressants, antiepileptics, or beta blockers are no longer taking these medications at 6 months.

Background The purpose of this study was to compare pre- and post-surgical healthcare costs in commercially insured total joint arthroplasty (TJA) patients with osteoarthritis (OA) in the United States (U.S.). Methods Using a large healthcare claims database, we identified patients over age 39 with hip or knee OA who underwent unilateral primary TJA (hip or knee) between 1/1/2006 and 9/30/2007. Utilization of healthcare services and costs were aggregated into three periods: 12 months "pre-surgery," 91 days "peri-operative," and 3 to 15 month "follow-up," Mean total pre-surgery costs were compared with follow-up costs using Wilcoxon signed-rank test. Results 14,912 patients met inclusion criteria for the study. The mean total number of outpatient visits declined from pre-surgery to follow-up (18.0 visits vs 17.1), while the percentage of patients hospitalized increased (from 7.5% to 9.8%) (both p < 0.01). Mean total costs during the follow-up period were 18% higher than during pre-surgery ($11,043 vs. $9,632, p < 0.01), largely due to an increase in the costs of inpatient care associated with hospital readmissions ($3,300 vs. $1,817, p < 0.01). Pharmacotherapy costs were similar for both periods ($2013 [follow-up] vs. $1922 [pre-surgery], p = 0.33); outpatient care costs were slightly lower in the follow-up period ($4338 vs. $4571, p < 0.01). Mean total costs for the peri-operative period were $36,553. Conclusions Mean total utilization of outpatient healthcare services declined slightly in the first year following TJA (exclusive of the peri-operative period), while mean total healthcare costs increased during the same time period, largely due to increased costs associated with hospital readmissions. Further study is necessary to determine whether healthcare costs decrease in subsequent years.

OBJECTIVE To estimate direct and indirect economic costs among private-sector employees with osteoarthritis (OA). METHODS Using a large US employer benefits database, we identified all employees with evidence of OA during calendar year 2007, and compared their costs of health care and work loss to age-and-sex-matched employees without evidence of OA in that year. RESULTS Private-sector employees with OA (n = 2399) averaged 62.9 days of absenteeism versus 36.7 days among matched comparators (n = 2399) (P < 0.01). Mean total direct costs among these persons were $17,751 and $5057, respectively (P < 0.01); 34% of health care costs among persons with OA arose from medical encounters with listed diagnoses of OA. Mean total indirect costs were two-fold higher among persons with OA ($5002 versus $2120 for those without OA; P < 0.01). CONCLUSIONS Private-sector employees with OA have higher direct and indirect costs than those without this condition.

To compare healthcare utilization and costs in the year preceding and following initial diagnosis of fibromyalgia (FM).Using a large US health insurance claims database, we identified all persons with newly diagnosed FM (International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 729.1) between January 1, 2003, and December 31, 2005 ("FM patients"). Each patient's first-noted claim with a diagnosis of FM was designated the "index date," and all pharmacy, outpatient, and inpatient claims were compiled over the 12-month periods preceding and following this date ("prediagnosis" and "postdiagnosis," respectively). Patients with incomplete pre- or postdiagnosis data were excluded. Healthcare utilization and costs were compared between the 2 periods.A total of 1803 patients met all study inclusion criteria; mean (SD) age was 50.4 (9.4) years; 91% were women. Comorbidities were common, including arthritis (21% of study subjects), back pain (20%), and painful neuropathic disorders (16%). The percentage of study subjects receiving various pain-related medications increased from pre- to postdiagnosis, including opioids (51.3% vs 55.9%), antiepileptics (22.6% vs 28.6%), and tricyclic antidepressants (15.5% vs 21.2%) (all P.01). Mean total healthcare costs also increased by $1725 between these periods (mean [95% confidence interval]: $9324 [$8655, $10,092] vs $11,049 [$10,245, $11,973], respectively; P.01).Patients with FM are often seen for other medical problems prior to initial diagnosis. Levels of healthcare utilization and costs are high during both the pre- and postdiagnosis periods.

Tacrolimus 0.1% and pimecrolimus 1.0% are used for short-term and noncontinuous treatment of atopic dermatitis (AD) in patients unresponsive to conventional therapies.To assess the cost-effectiveness of tacrolimus versus pimecrolimus in adults with AD.Using a Markov cohort model, the authors projected clinical and economic outcomes over six weeks in adults receiving tacrolimus versus pimecrolimus. Cost-effectiveness was assessed in terms of the ratio of the expected cost of AD-related care to the expected number of days with resolved AD.Patients receiving tacrolimus had an estimated 4.9 fewer days with active AD over six weeks (30.0 versus 34.9 for pimecrolimus). Expected costs (per patient) of AD-related care also were lower for tacrolimus patients ($501.27 versus $546.14, respectively).While pimecrolimus is indicated for use solely in patients with mild-to-moderate AD, the trial on which this study was based included some patients with severe AD.In adults with AD, tacrolimus 0.1% may yield better clinical outcomes and lower costs of care than pimecrolimus 1.0%.

To compare healthcare utilization and costs in patients with end-stage renal disease (ESRD) beginning peritoneal dialysis (PD) or hemodialysis (HD).Retrospective cohort study.Using a US health insurance database, we identified all patients with ESRD who began dialysis between January 1, 2004, and December 31, 2006. Patients were designated as PD patients or as HD patients based on first-noted treatment. Patients with less than 6 months of pretreatment data and those with less than 12 months of data following initiation of dialysis ("pretreatment" and "follow-up," respectively) were dropped from the study sample. The PD patients were matched to HD patients using propensity scoring to control for differences in pretreatment characteristics. Healthcare utilization and costs were then compared over 12 months between propensity-matched PD patients and HD patients using paired t tests and Wilcoxon signed rank tests for continuous variables and using Bowker and McNemar tests for categorical variables, as appropriate.A total of 463 patients met all study entrance criteria; 56 (12%) began treatment with PD, and 407 (88%) began treatment with HD. Fifty PD patients could be propensity matched to an equal number of HD patients. The HD patients were more than twice as likely as matched PD patients to be hospitalized over the subsequent 12 months (hazard ratio, 2.17; 95% confidence interval, 1.34-3.51; P.01). Their median healthcare costs over the 12-month follow-up period were $43,510 higher ($173,507 vs $129,997 for PD patients, P = .03).Among patients with ESRD, PD patients are less likely than HD patients to be hospitalized in the year following initiation of dialysis. They also have significantly lower total healthcare costs.

Background Several medications commonly used to treat generalized anxiety disorder (GAD) have been designated "potentially inappropriate" for use in patients aged ≥65 years because their risks may outweigh their potential benefits. The actual extent of use of these agents in clinical practice is unknown, however. Methods Using a database with information from encounters with general practitioners (GP) in Germany, we identified all patients, aged ≥65 years, with any GP office visits or dispensed prescriptions with a diagnosis of GAD (ICD-10 diagnosis code F41.1) between 10/1/2003 and 9/30/2004 ("GAD patients"). Among GAD-related medications (including benzodiazepines, tricyclic antidepressants [TCAs], selective serotonin reuptake inhibitors, venlafaxine, hydroxyzine, buspirone, pregabalin, and trifluoperazine), long-acting benzodiazepines, selected short-acting benzodiazepines at relatively high dosages, selected TCAs, and hydroxyzine were designated "potentially inappropriate" for use in patients aged ≥ 65 years, based on published criteria. Results A total of 975 elderly patients with GAD were identified. Mean age was 75 years, and 72% were women; 29% had diagnoses of comorbid depression. Forty percent of study subjects received potentially inappropriate agents – most commonly, bromazepam (10% of all subjects), diazepam (9%), doxepin (7%), amitriptyline (5%), and lorazepam (5%). Twenty-three percent of study subjects received long-acting benzodiazepines, 10% received short-acting benzodiazepines at relatively high doses, and 12% received TCAs designated as potentially inappropriate. Conclusion GPs in Germany often prescribe medications that have been designated as potentially inappropriate to their elderly patients with GAD – especially those with comorbid depressive disorders. Further research is needed to ascertain whether there are specific subgoups of elderly patients with GAD for whom the benefits of these medications outweigh their risks.

Background and Objectives: To describe patterns of healthcare utilization among patients with generalized anxiety disorder (GAD) in general practitioner (GP) settings in Germany. Methods: Using a large computerized database with information from GP practices across Germany, we identified all patients, aged > 18 years, with diagnoses of, or prescriptions for, GAD (ICD-10 diagnosis code F41.1) between October 1, 2003 and September 30, 2004 ("GAD patients"). We also constituted an age- and sex-matched comparison group, consisting of randomly selected patients without any GP encounters or prescriptions for anxiety or depression (a common comorbidity in GAD) during the same period. GAD patients were then compared to those in the matched comparison group over the one-year study period. Results: The study sample consisted of 3340 GAD patients and an equal number of matched comparators. Mean age was 53.2 years; 66.3% were women. Over the 12-month study period, GAD patients were more likely than matched comparators to have encounters for various comorbidities, including sleep disorders (odds ratio [OR] = 6.75 [95% CI = 5.31, 8.57]), substance abuse disorders (3.91 [2.89, 5.28]), and digestive system disorders (2.62 [2.36, 2.91]) (all p < 0.01). GAD patients averaged 5.6 more GP encounters (10.5 [SD = 8.8] vs 4.9 [5.7] for comparison group) and 1.4 more specialist referrals (2.3 [2.9] vs 0.9 [1.7]) (both p < 0.01). Only 58.3% of GAD patients received some type of psychotropic medication (i.e., benzodiazepines, antidepressants, and/or sedatives/hypnotics). Conclusions: Patients with GAD in GP practices in Germany have more clinically recognized comorbidities and higher levels of healthcare utilization than patients without anxiety or depression.

Using a large database with information from general practitioners (GP) throughout Germany, we identified all adults (age > or = 18 years) with encounters for painful neuropathic disorders (PNDs) between August 1, 2005 and July 31, 2006 (PND patients). We also constituted an age- and sex-matched comparison group, consisting of randomly selected patients without any GP encounters for PNDs during the same period. Selected characteristics were then compared between PND patients and those in the comparison group over the 1-year study period. The study sample consisted of 275,685 PND patients and a similar number in the matched comparison group; mean age was 53.7 years, and 57% were women. PND patients were more likely than matched comparators to have encounters for various comorbidities, including circulatory system disorders (47% vs. 20%, respectively), depression (9% vs. 2%), and anxiety (4% vs. 1%) (all P < 0.01). They also were more likely to have received pain-related medications (57% vs. 13% for comparison group; P < 0.01)--most commonly, nonsteroidal anti-inflammatory drugs, benzodiazepines, and opioids, and less often, tricyclic antidepressants and anti-epileptics. PND patients averaged 7.3 more GP visits during the year (mean [95% CI] = 9.9 [9.9, 9.9] vs. 2.6 [2.6, 2.7] for comparison group); they also had significantly more specialist referrals and physician-excused absences from work (all P < 0.01). Patients with PNDs under the care of GPs in Germany have comparatively more comorbidities and higher levels of use of healthcare services. The pain-related medications that these patients receive raise concerns that PNDs may not be optimally treated in these settings.

Objective.To estimate the consequences of failure of initial antibiotic therapy for patients with complicated skin and skin-structure infections.Design.Retrospective cohort study.Setting.Large US multihospital database.Patients.We identified a total of 47,219 patients (age 18 years or older) who were admitted to the hospital for complicated skin and skin-structure infections from April 1, 2003, through March 31, 2004, and who received intravenous antibiotics during the first 2 hospital-days (ie, initial antibiotic therapy). Failure of therapy was defined as drainage, debridement, or receipt of other intravenous antibiotics at any subsequent time (except for changes to narrower-spectrum agents or any therapy change immediately before discharge). Predictors of failure of antibiotic therapy and mortality were examined using multivariate logistic regression. Analysis of covariance was used to estimate the impact of treatment failure on duration of intravenous antibiotic therapy, length of stay, and total inpatient charges.Results.For 10,782 admitted patients (22.8%), there was evidence of failure of initial antibiotic therapy. In multivariate analyses, treatment failure was associated with receipt of vasoactive medications during the first 2 hospital-days (odds ratio [OR], 1.66 [95% confidence interval {CI}, 1.19-2.31]), initiation of antibiotic therapy in the intensive care unit (OR, 1.53 [95% CI, 1.28-1.84]), and the patient's Charlson comorbidity index (OR per 1-point increase, 1.06 [95% CI, 1.04-1.08]); treatment failure was also was associated with a 3-fold increase in mortality (OR, 2.91 [95% CI, 2.34-3.62]). Compared with patients for whom initial treatment was successful, patients who experienced treatment failure received intravenous antibiotic therapy for a mean of 5.7 additional days, were hospitalized for a mean of 5.4 additional days, and incurred a mean of $5,285 (in 2003 dollars) in additional inpatient charges (all P Conclusion.Failure of initial antibiotic therapy in the treatment of complicated skin and skin-structure infections is associated with significantly worse clinical and economic outcomes.

Purpose To describe patterns of use of tricyclic antidepressants (TCAs) (eg, amitriptyline, nortriptyline) among older patients with diabetic peripheral neuropathy (DPN). Materials and methods Using a large, integrated, US health-insurance claims database, we identified all patients who received TCAs between January 1, 1999 and June 30, 2001 ("study period"). Among these persons, we then selected those who: (1) were aged >or=65 years as of the date of first receipt of a TCA during the study period; and (2) had one or more healthcare encounters with a diagnosis of DPN in the 30-day period immediately preceding date of first receipt of a TCA. We then examined the prevalence of selected comorbidities and concurrent use of medications which might render inappropriate the prescribing of TCAs, based on a listing of contraindications, warnings, and precautions found in the package inserts for these medications. Patterns of TCA prescribing were examined, based on information on paid claims. Results There were 349 DPN patients, aged >or=65 years, who received TCAs. Mean age was 73.8 years, 55.9% were women, and 17.9% had diagnoses of depression. Most patients (84.0%) began therapy with amitriptyline. Almost one-half of study patients had indicators of potentially inappropriate TCA use, primarily cardiovascular comorbidities. Mean TCA dose among patients with and without these indicators was 23.3 (+/-13.4) mg and 25.4 (+/-15.3) mg, respectively (P=0.42). Conclusions The high prevalence of contraindications, warnings, or precautions and the low level of TCA exposure suggest that many older patients with DPN who receive TCAs may be inappropriately treated.

Background: Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option for many hematologic malignancies, but is associated with numerous complications, including infection. While the clinical consequences of infection post-HCT have been well characterized, details of their economic burden have not. Methods: Using a large US healthcare claims database, we identified patients aged ≥2 years who underwent allogeneic HCT between October 2009 and March 2013. The hospital admission during which HCT was performed was deemed the "Index Admission". We excluded patients without continuous health plan enrollment and evidence of a hematologic malignancy in the 6-month period prior to the Index Admission. Patients were followed from discharge of the Index Admission until death, plan disenrollment, or one year, whichever occurred first ("Follow-Up"). We ascertained the incidence of infections during the Index Admission through 100 days after discharge ("Early Infections"), and examined by etiology (bacterial, viral, fungal, other/unknown) using relevant ICD-9-CM diagnosis codes. We then ascertained total healthcare costs (inpatient care, outpatient care, outpatient pharmacy) and hospital length of stay (LOS) during the Index Admission and Follow-Up. Reimbursed amounts (plan payment plus patient liability) were used as a proxy for healthcare costs. We compared total healthcare costs and LOS during the Index Admission, Follow-Up, and Overall (Index Admission + Follow-Up) between patients who did versus did not experience an Early Infection using Student's t-tests (unadjusted analyses), and analyses of covariance (ANCOVA) to adjust for differences in age, sex, plan type, geography, year of Index Admission, type of malignancy, and comorbidities. Results: A total of 1,635 patients were identified who underwent allogeneic HCT and met all selection criteria; mean age was 48.4 years, 55.6% were men, and acute myeloid leukemia was the most common malignancy (41.8%). A total of 77.7% of patients (n=1,270) experienced ≥1 Early Infections: bacterial (45.5%), viral (33.2%), fungal (19.5%), and other/unknown (54.1%). Univariate findings are presented in the table. Compared to patients without Early Infections, multivariate-adjusted mean total healthcare costs among patients with Early Infection were $69,044 greater during Index Admission, $74,307 greater during Follow-Up, and $143,351 greater Overall; corresponding increases in LOS were 8 days, 10 days, and 18 days, respectively (all p Conclusions: Nearly four-in-five patients who undergo allogeneic HCT experience Early Infections. These infections are associated with significant increases in healthcare costs and hospital LOS. Our findings suggest new therapies capable of preventing infection - especially across etiologies- could be impactful from an economic perspective. Table 1. Mean (SD) Total LOS and Healthcare Costs, by Time Since Allogeneic HCT and Early Infection Status Type of Infection Overall Index Admission Follow-Up Period WITHInfection WITHOUT Infection p-value WITH Infection WITHOUT Infection p-value WITH Infection WITHOUT Infection p-value Total LOS, days Any Infection 56.9 (41.8) 38.0 (25.2) Disclosures Berger: Evidera: Employment; Fate Therapeutics, Inc: Research Funding. Grubb:Fate Therapeutics, Inc: Employment, Equity Ownership. Huse:Fate Therapeutics, Inc: Research Funding; Evidera: Employment. Mohanty:Evidera: Employment; Fate Therapeutics, Inc: Research Funding. Ferraro:Fate Therapeutics, Inc: Employment, Equity Ownership. Daniels:Fate Therapeutics, Inc: Employment, Equity Ownership. Levin:Fate Therapeutics, Inc: Employment, Equity Ownership.

Using a large US health insurance claims database, we identified all persons aged > or =18 years with > or =2 medical encounters with diagnoses of cancer and > or =2 medical encounters with diagnoses of painful neuropathies in calendar year (CY) 2000; persons with seizure disorders or depression were excluded. We then examined the use of antiepileptics (AEDs), tricyclic antidepressants (TCAs) and other pain-related pharmacotherapy among these selected persons, as proxied by pharmacy dispenses. A total of 956 persons were identified who met all entry criteria; 17% received AEDs in CY2000 and 14% received TCAs. Gabapentin was the most widely used AED (92% of all AED patients); amitriptyline was the most widely used TCA (79% of all TCA patients). Patients who received AEDs and/or TCAs were similar in age, gender and the presence of metastases to those who had not received these medications; they were more likely to have received other pain-related therapies, however, including short-acting opioids (73% vs. 53%; P < 0.01) and long-acting opioids (23% vs. 8%; P < 0.01). Use of AEDs and TCAs appears to be relatively low among cancer patients with painful neuropathies. Further research is needed to better understand reasons for this finding, as well as its potential implications for pain management in this patient population.

To describe patterns of use of tricyclic antidepressants (TCAs) (e.g., amitriptyline, nortriptyline) in older patients with painful neuropathies.Using a large US health insurance claims database, we identified all persons who: (1) received a TCA between 1 January 1999 and 30 June 2001, (2) were agedor =65 years as of the date of their first prescription for a TCA during this period, and (3) had one or more health care encounters for the treatment of a painful neuropathy in the 30-day period immediately preceding their initial receipt of a TCA. We then examined the prevalence of selected comorbidities and/or concurrent use of medications that might render the prescribing of a TCA inappropriate, based on a listing of contraindications, warnings, and precautions found in the package inserts for these agents. Patterns of TCA use also were examined, based on information on paid claims.A total of 1,732 patients met all inclusion and exclusion criteria for the study. Their mean age was 74.6 years; 60.3% were women. Amitriptyline was the most frequently prescribed TCA (79.4% of patients). Forty-one percent of study subjects receiving TCAs had conditions--primarily cardiovascular--that render the use of such agents potentially inappropriate. The mean daily dose of TCAs was universally low (about 23 mg).The high prevalence of conditions rendering the use of TCAs potentially inappropriate, along with relatively low daily dosages, suggest that many older patients with painful neuropathies who are prescribed these agents may be suboptimally treated.

BACKGROUND Infliximab, in combination with methotrexate, is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA). While there is anecdotal evidence that many patients beginning infliximab therapy have their dose and/or frequency of infusions increased over time (“dose intensification”), relatively little is known about actual patterns of use in clinical practice. OBJECTIVE To examine patterns of infliximab use in patients with RA. METHODS Using a large US healthcare claims database, all patients with RA who initiated infliximab therapy between January 1, 2000, and September 30, 2001, were identified. The date of each patient's first claim for infliximab was identified and designated as the index date; attention was limited to patients who received infliximab for at least one year. Patterns of infliximab use were then examined over the 12-month period following the index date, based on information on paid claims. RESULTS Fifty-three patients met all entry criteria; the mean age was 61 years, and 81% were women. Twenty-eight percent of patients received >8 infusions over 12 months. The mean dose of infliximab at initial infusion was 296.2 mg; at final infusion, it was 401.9 mg (36% increase). One-half of study subjects had their dose of infliximab increased by ≥30% between the initial and final infusions; one-third had their dose increased by ≥50%. CONCLUSIONS Many patients with RA beginning treatment with infliximab have their frequency of infusions and/or medication dose increased within the first 12 months.

Although older adults with painful neuropathic disorders (PNDs) would appear to be at elevated risk for receiving potentially inappropriate pain-related medications, the extent of such drug use in this population is unknown.The goal of this study was to assess the use of potentially inappropriate pain-related medications among patients with PNDs agedor=65 years.Using a large, integrated US health insurance database, we identified all persons agedor=65 years withor=2 medical encounters involving diagnoses of PNDs during calendar year 2000. Patients with30 days of continuous eligibility for health benefits during the study year were excluded from the sample. Use of potentially inappropriate pain-related medications (as defined by the 1997 Beers criteria) was then examined based on information contained in paid pharmacy claims for all remaining patients.We identified 22,668 patients with PNDs agedor=65 years (mean [SD] age, 73.9 [6.0] years; 58.6% female). Almost one half (11,233 [49.6%]) of patients receivedor=1 potentially inappropriate pain-related medication, including propoxyphene (26.7%) and amitriptyline (10.2%). Women were more likely than men to receive these medications (54.2% vs 43.0%, respectively; P0.01), and use increased with age (47.6%, 51.8%, and 52.8% in those aged 65-74 years, 75-84 years, andor=85 years, respectively; overall comparison, P0.01). Among patients with only 1 PND, the use of potentially inappropriate medications was highest among those with postherpetic neuralgia (70.1%).Use of potentially inappropriate pain-related medications among older adults with PNDs is common. Further research is needed to ascertain whether the benefits of these agents outweigh their risks in this population.

Opioid use and health care charges during the final year of life in patients with metastatic cancer who received controlled-release oxycodone (CRO), transdermal fentanyl (TF), or controlled-release morphine sulfate (CRM) were examined in the following study. A total of 704 patients were identified who met study entry criteria; CRO, TF, or CRM was the first-received long-acting opioid (LAO) during the last year of life for 36% (N = 250), 29% (N = 203), and 36% (N = 251) of study subjects, respectively. On average, patients initiated LAO therapy three to four months before death. One-half of patients received less than 60 days of LAO therapy. Mean total health care charges in the final year of life were dollars 84,572 for patients receiving CRO, dollars 90,935 for patients receiving TF, and dollars 76,446 for patients receiving CRM. Patients receiving TF started LAO therapy closer to their date of death, and had significantly higher hospitalization charges than did patients receiving CRO and CRM.

BACKGROUND Patterns of therapy switching in patients receiving long-acting opioids have not been well documented. OBJECTIVE To compare therapy switching among patients beginning treatment with controlled-release (CR) oxycodone, transdermal fentanyl, or CR morphine sulfate. METHODS Using a US healthcare claims database, we identified patients beginning treatment with CR oxycodone, transdermal fentanyl, or CR morphine sulfate between July 1, 1998, and December 31, 1999. We compiled claims for each patient for 6 months following therapy initiation and compared the incidence of therapy switching among the 3 groups. We also estimated total healthcare charges for patients who switched therapy versus those who did not. RESULTS We identified 1931, 668, and 449 patients beginning therapy with CR oxycodone, transdermal fentanyl, and CR morphine sulfate, respectively; 16.7%, 25.0%, and 35.9%, respectively, had cancer. For patients without cancer, rates of therapy switching at 6 months were 10.6% (CR oxycodone), 19.0% (transdermal fentanyl), and 26.0% (CR morphine sulfate); for those with cancer, rates were 23.8%, 24.6%, and 29.8%, respectively. Multivariate hazard ratios (vs CR morphine sulfate) for therapy switching in patients without cancer were 0.36 (95% CI, 0.27 to 0.47) for CR oxycodone and 0.69 (0.51 to 0.94) for transdermal fentanyl; for those with cancer, corresponding hazard ratios were 0.72 (0.50 to 1.03) and 0.76 (0.50 to 1.16). Total healthcare charges were significantly (p < 0.01) higher for patients who switched therapy than those who did not ($23 965 vs $14 299 in pts. without cancer; $58 259 vs $39 618 for those with cancer). CONCLUSIONS Patients without cancer who receive CR oxycodone or transdermal fentanyl are less likely to switch therapy than those receiving CR morphine sulfate. Total healthcare charges are higher for patients who switch therapy.

This study documents the use of oral and transdermal opioids among patients with metastatic cancer during their final year of life. Using a large, integrated health-insurance claims database, we identified all patients who had metastatic lung, breast, colorectal, prostate, or breast cancer and who also died in 1998 or 1999. We then examined all pharmacy claims for these patients over their final 12 months of life. A total of 2,132 patients were identified who met study entrance criteria. Among patients with bone metastases (n=717), 86.9% received opioids at some point during their final year of life; 71.2% of those without bone metastases (n=1,415) received them. Corresponding figures for long-acting opioids were 52.9% and 23.5%. Coverage ratios (total days supplied/total noninstitutionalized days) for any opioids and long-acting opioids were 25.1% and 12.5%, respectively, among patients with bone metastases, and 13.9% and 4.2% for those without bone metastases. During the final month of life, these ratios were 50.8% and 31.3%, and 28.7% and 13.1%. These relatively low rates of opioid use among patients with metastatic cancer in their final year of life suggest that pain in many cases may be suboptimally treated.

Introduction The efficacy and safety of the novel agents, lenalidomide and bortezomib, in previously untreated MM has been demonstrated in several randomized controlled trials (Online-OnlyTs). In this study, we examine the cost-effectiveness of lenalidomide-melphalan–prednisone induction followed by lenalidomide maintenance (MPR-R), and bortezomib-melphalan-prednisone (VMP), respectively, versus melphalan-prednisone (MP), in patients with previously untreated MM. Methods We developed a partitioned-survival model to estimate expected clinical outcomes and costs in newly diagnosed MM patients receiving MPR-R, VMP, or MP as first-line therapy. The model had 3 mutually exclusive health states: (1) “progression-free, alive”; (2) “post-progression, alive”; and (3) “death.” Progression-free survival (PFS) for MP was estimated by aggregating data across five Online-OnlyTs (Palumbo 2012, San Miguel 2008, Facon 2007, Hulin 2009, Palumbo 2006). Estimates of PFS for MPR-R and VMP were based on an adjusted indirect treatment comparison with MP, using data from MM-015 for MPR-R (Palumbo 2012) and VISTA for VMP (San Miguel 2008). Since many MP patients in both MM-015 and VISTA “crossed over” to lenalidomide and bortezomib following disease progression in these trials, we estimated post-progression survival (PPS) for MPR-R and VMP based on a review of novel agents in MM (Messori 2011), which reported mean PPS of 30.9 months. Costs of MPR-R and VMP were estimated based on actual use of study drug in Online-OnlyTs; costs of adverse events as well as other disease-related costs were estimated based on published data. Health-state utilities also were estimated using published data. All costs were expressed in 2012 US$. Cost-effectiveness of MPR-R and VMP versus MP was examined in terms of cost per life-year (LY) gained, cost per quality-adjusted life-year (QALY) gained, and cost per progression-free life-year gained. Future costs and benefits were discounted at 3% annually. Results Mean estimated PFS was 3.4 years for MPR-R, 2.6 years for VMP, and 1.7 years for MP; corresponding estimates for OS were 6.0 years, 5.2 years, and 4.3 years, respectively (Table 1). Mean total expected lifetime costs (discounted) are reported in the Table. The incremental cost per life-year (LY) gained versus MP was $75,392 for MPR-R and $86,213 for VMP; corresponding estimates of the incremental cost per QALY gained were $91,794 and $106,211, respectively (Figure 1). The incremental cost per progression-free LY (PFLY) gained versus MP was $70,666 for MPR-R and $80,565 for VMP. Conclusions In patients with previously untreated MM, cost-effectiveness ratios for MPR-R and VMP are well within the range reported for other well-accepted novel therapies in oncology. $/LY: Incremental cost per life-year gained; $/QALY: Incremental cost per quality-adjusted life-year gained; $/PFLY: Incremental cost per progression-free life-year gained Support Funded by Celgene Corporation Disclosures: Oster: Celgene: Research Funding. Off Label Use: Lenalidomide (immunomodulatory agent), bortezomib (proteosome inhibitor), melphalan (alkylator), and prednisone (steroid), are all treatments for multiple myeloma. Berger:Celgene: Research Funding. Bornheimer:Celgene: Research Funding. Binder:Celgene: Employment, Equity Ownership. Nagarwala:Celgene: Employment, Equity Ownership.

17082 Background: mTC is relatively rare and little is known about treatment patterns or HC costs in patients with newly diagnosed disease. Methods: Retrospective longitudinal cohort study. Using a large (∼14 million covered lives) US health-insurance claims database, we identified a cohort of pts with diagnoses of thyroid cancer (ICD-9-CM diagnosis codes 193.XX) and distant metastatic disease (197.XX-198.XX) between 1/1/2003 and 12/31/2005 (“study period”); the date of first mention of metastatic disease was designated the “index date”. All pts were required to be =18 years of age as of their index date and to have been continuously enrolled in the database for =6 months prior to this date. Pts were followed from their index date until health plan disenrollment (for any reason) or end of the study period, whichever occurred first. Utilization of HC services and costs (total reimbursed amount including pt liability) were then examined during each quarter of follow-up (eg, first 3 months of follow-up=Q1). Results: 183 pts met all study entry criteria. Mean (±SD) age was 51.5 (11.8) years; mean duration of follow-up was 344 days (median=275 days). Most common management/treatment strategies during Q1 included: imaging [eg, US/CT of the neck (49.7%)], thyroglobulin/thyroglobulin antibody testing (25.7%); radiation therapy (23.0%); I131 therapy (19.1%); thyroid surgery (12.6%); chemotherapy (10.9%); lymphadenectomy (8.7%); and bisphosphonate therapy (3.8%). In addition, during Q1, pts averaged 9.5 office visits (95% CI, 8.2, 10.9) and 0.6 hospitalizations (95% CI, 0.5, 0.7); for pts hospitalized during Q1, average length of stay was 6.6 (95% CI, 4.9, 8.4). Costs during the first 2 years of follow-up are presented in the table ; inpt care represented 43% of total HC costs. Conclusions: Many different treatment modalities are used in pts with newly diagnosed mTC; the cost of such care is substantial. [Table: see text] [Table: see text]