Large Retrospective Database Research Articles

Pediatric reduction mammaplasty: A retrospective analysis of the Kids' Inpatient Database (KID)

Pediatric breast reduction mammaplasty is a procedure commonly performed in children suffering from excess breast tissue, back pain, and social anxiety. Minimal information exists regarding demographics, epidemiology, and complications in adolescents. As health care reform progresses, investigating the socioeconomic and patient-related factors affecting cost and operative outcomes is essential. The Kids' Inpatient Database (KID) was used from 2000 to 2009. Patients with an International Classification of Diseases, 9th Revision code of macromastia and procedure code of reduction mammaplasty 20 and less were included. Demographic data, including age, sex, payer mix, and location, were collected. Significant independent variables associated with complications and duration of stay were identified with bivariate and multiple regression analysis. A total of 1,345 patients between the ages 12 and 20 were evaluated. The majority of patients were white (64%), from a zip code with greatest income (36%), and had private insurance (75%). Overall comorbidity and complication rates were 30% and 3.2%, respectively. Duration of stay was associated with race, income quartile, insurance type, having complications, and hospital type. African-American race, Medicaid, lower income, and private-investor owned hospitals were predictive of greater hospital charges. In this large retrospective database analysis, pediatric reduction mammaplasty had a relatively low early complication rate and short duration of stay. Complications, total charges, and duration of stay discrepancies were associated with race, location, and socioeconomic status. Although demonstrably safe, this is the first study demonstrating the negative effect of race and socioeconomic status on a completely elective procedure involving children. These results demonstrate the intricate association between socioeconomic and patient-related factors influencing overall outcomes in the pediatric population.

PC138. Revised Cardiac Risk Index: An Effective Prognostic Tool for Vascular Postoperative Outcomes

The Revised Cardiac Risk Index (RCRI) is a tool clinicians use for preoperative risk stratification and predicting the likelihood of cardiac complications. This study looked at the role of the RCRI for postoperative outcomes in vascular patients undergoing lower extremity bypass surgery. National Surgical Quality Improvement Program data from 2005 to 2011 of patients undergoing lower extremity revascularization based on Current Procedural Terminology codes were analyzed looking at demographics, revised cardiac risk index variables (coronary heart disease, congestive heart failure, creatinine >2, insulin-dependent diabetes, high-risk surgery, cerebrovascular disease), and outcomes including operative time, days until graft failure, hospital length of stay (LOS), return to operating room, and death. Data were analyzed using single and multivariable linear and logistical regression. A total of 70,440 patients were included, with 25,176 female and 45,264 male patients. Of the 70,400 patients 40,893 (58%) were aged >65 years, with 27,576 (39%) aged between 46 and 65 years. Linear regression showed that with each point increase of the RCRI, operative time increases 5.4 minutes (P < .0001), LOS increases 3.23 days (P < .0001), and graft patency decreases by 0.5 days (P < .05). Through logistic regression, with each point increase in the RCRI the risk of returning to operating room increases 1.4 times (odds ratio, 1.449; 95% confidence interval, 1.412-1.486) and the risk of death increases 1.97 times (odds ratio, 1.972; 95% confidence interval, 1.867-2.083). Using a large retrospective national database, preoperative RCRI can be a useful measure for predicting postoperative outcomes in patients undergoing lower extremity bypass surgery.

Interpreting outcome data in hematopoietic cell transplantation for leukemia: tackling common biases.

Although patient outcomes after allogeneic hematopoietic cell transplantation (allo-HCT) have significantly improved in recent years, complications and associated mortality remain substantial. Although many transplants are performed worldwide, the number of patients enrolled prospectively into clinical trials is small. Patient and physician preferences often override treatment assignments in randomized transplant trials, biasing the common intention-to-treat analyses. Large retrospective and observational database studies are likely to detect the real effect of allo-HCT. However, they may be subject to immortal time and other biases derived from heterogeneity of allo-HCT indications and approaches and differences in referral or institutional policies affecting patient selection. Timing of the transplant procedure may be fundamental but studies commencing at start of transplant may neglect the influence of pretransplant therapies. Conversely, a prolonged lag period between the decision and execution of transplant may artificially 'improve' the outcome by 'natural' selection weeding out patients relapsing or dying before transplant. Finally, comparative nonrandomized transplantation trials often suffer from unbalanced assignment for therapy arms. We herein present common clinical dilemmas discussing proper application of available evidence in daily clinical practice. Pitfalls and caveats frequent in clinical studies of allo-SCT are highlighted to promote a balanced interpretation of available data.

Acute acalculous cholecystitis in the critically ill: risk factors and surgical strategies.

Acute acalculous cholecystitis (AAC) is characterized by severe gallbladder inflammation without cystic duct obstruction. Critical illness and neurological deficits are often associated with AAC, and early radiologic imaging is necessary for the detection and timely treatment of AAC. In critically ill patients, effective surgical management is difficult. This review examines the three common surgical treatments for AAC (open cholecystectomy (OC), laparoscopic cholecystectomy (LC), or percutaneous cholecystostomy (PC)), their prevalence in current literature, and the perioperative outcomes of these different approaches using a large retrospective database. This review examined literature gathered from PubMed and Google Scholar to select more than 50 sources with data pertinent to AAC; of which 20 are described in a summary table. Outcomes from our previous research and several updated results were obtained from the University HealthSystem Consortium (UHC) database. LC has proven effective in treating AAC when the risks of general anesthesia and the chance for conversion to OC are low. In critically ill patients with multiple comorbidities, PC or OC may be the only available options. Data in the literature and an examination of outcomes within a national database indicate that for severely ill patients, PC may be safer and met with better outcomes than OC for the healthier set of AAC patients. We suggest a three-pronged approach to surgical resolution of AAC. Patients that are healthy enough to tolerate LC should undergo LC early in the course of the disease. In critically ill patients, patients with multiple comorbidities, a high conversion risk, or who are poor surgical candidates, PC may be the safest and most successful intervention.

The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: Proposal for an Evidence-Based Stage Classification System for the Forthcoming (8th) Edition of the TNM Classification of Malignant Tumors

A universal and consistent stage classification system, which describes the anatomic extent of a cancer, provides a foundation for communication and collaboration. Thymic epithelial malignancies have seen little progress, in part because of the lack of an official system. The International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group assembled a large retrospective database, a multispecialty international committee and carried out extensive analysis to develop proposals for the 8th edition of the stage classification manuals. This tumor, node, metastasis (TNM)-based system is applicable to all types of thymic epithelial malignancies. This article summarizes the proposed definitions of the T, N, and M components and describes how these are combined into stage groups. This represents a major step forward for thymic malignancies.

PDB64 - Comparative cost-effectiveness of becaplermin gel on wound healing and amputation in patients with diabetic foot ulcer

Determine the cost-effectiveness of becaplermin gel* on wound healing and amputation for the treatment of diabetic foot ulcers (DFUs). A 4-stage Markov model was used to predict the expected costs and outcomes of wound healing and amputation rates for becaplermin and non-becaplermin DFU cohorts over a 1-year time period. Outcome data used in the analysis were derived from a propensity score matched cohort of 24,898 subjects with DFU from the Curative Health Services database from 1998-2004 who were followed for 20 weeks. Primary outcomes of interest were ulcer-free weeks and rates of amputation. Costs for amputation and becaplermin gel*were derived from standard cost references and medical supply wholesalers. Total weekly costs per episode of DFU care were estimated from a large retrospective claims database. Transition probabilities for healing and amputation were derived from the aforementioned propensity score matched cohorts. Ulcer recurrence was estimated from the medical literature. Utilization for becaplermin was calculated using the manufacturer’s recommended dosing algorithm. The economic perspective taken was that of the payer. Costs are reported in 2013 US dollars. Overall, 2,394 (9.6%) received becaplermin. Of those who received becaplermin, 33.5% healed at 20 weeks compared to 26.5% who did not receive becaplermin (p<0.0001). In addition, the percent of patients requiring amputation were significantly (p<0.0001) lower in the becaplermin cohort (4.9% versus 6.4%, respectively). Patients treated with becaplermin had substantially higher ulcer-free weeks compared to non-becaplermin patients (16.1 versus 12.5 weeks, respectively). Expected annual direct costs for DFU were $20,885 for becaplermin and $23,506 for non-becaplermin. Becaplermin was economically dominant over standard therapy, providing better outcomes at a lower cost in patients with DFU. In addition, becaplermin is more effective in wound healing and preventing amputation, thereby decreasing long-term costs for DFU. *Regranex®, Smith & Nephew Biotherapeutics, Fort Worth, Texas

Sentinel Events in Cervical Spine Surgery

Retrospective cohort. A national population-based database was queried to investigate the incidence of sentinel events in cervical spine surgery as well as the associated perioperative outcomes. Sentinel events in cervical spine surgery are potentially catastrophic complications. The incidence and perioperative outcomes associated with sentinel events in cervical spine surgery have not been well characterized. The Nationwide Inpatient Sample was queried from 2002 to 2011. Patients who underwent elective cervical spinal surgery were identified. Sentinel events including esophageal perforation, vascular injury, nerve injury, retention of foreign objects, and wrong-site surgery were identified. Patient demographics, comorbidities (Charlson Comorbidity Index), surgical procedures, length of stay, total hospital costs, and postoperative outcomes were assessed. The risk for in-hospital mortality associated with each complication was calculated using a 95% confidence interval (CI). Statistical analysis was performed with SPSS version 20, and a P ≤ 0.001 denoted significance. A total of 251,318 cervical spine procedures were identified between 2002 and 2011, of which 123 patients (0.5 per 1000 cases) incurred sentinel events. Circumferential cervical fusion (anterior-posterior cervical fusion) demonstrated an increased risk of vascular injury (odds ratio [OR], 4.5; CI, 1.8-11.2), whereas cervical total disc replacement was associated with an increased risk of esophageal perforation (OR, 10.9; CI, 1.4-85.2) and nerve injury (OR, 36.4; CI, 1.5-892.3). Posterior cervical fusions were associated with an increased risk of wrong-site surgery (OR, 3.9; CI, 1.5-10.5). The sentinel event cohort incurred longer hospitalization, greater costs, mortality, and greater incidence of postoperative complications. This database analysis demonstrates that sentinel events are associated with a significant increase in hospital resource utilization and worsened perioperative outcomes. The type of cervical spine procedure and the number of fusion levels significantly impact the risk of sentinel events. Further research is warranted to understand the etiology of sentinel events in cervical spine surgery and to implement protocols to mitigate the associated risk factors. 4.

Prediction of Survival in Resected Non–Small Cell Lung Cancer Using a Protein Expression–Based Risk Model: Implications for Personalized Chemoprevention and Therapy

Patients with resected non-small cell lung cancer (NSCLC) are at risk for recurrence of disease, but we do not have tools to predict which patients are at highest risk. We set out to create a risk model incorporating both clinical data and biomarkers. We assembled a comprehensive database with archival tissues and clinical follow-up from patients with NSCLC resected between 2002 and 2005. Twenty-one proteins identified from our preclinical studies as related to lung carcinogenesis were investigated, including pathways related to metabolism, DNA repair, inflammation, and growth factors. Expression of proteins was quantified using immunohistochemistry. Immunohistochemistry was chosen because it is widely available and can be performed on formalin-fixed paraffin-embedded specimens. Cox models were fitted to estimate effects of clinical factors and biomarkers on recurrence-free survival (RFS) and overall survival (OS). A total of 370 patients are included in our analysis. With median follow-up of 5.3 years, median OS is 6.4 years. A total of 209 cases with recurrence or death were observed. Multicovariate risk models for RFS and OS were developed including relevant biomarkers, age, and stage. Increased expression of phospho-adenosine monophosphate-activated protein kinase (pAMPK), phospho-mTOR (pmTOR), epithelial cell adhesion molecule (EpCAM), and calcium/calmodulin-dependent serine protein kinase were significant (P < 0.05) predictors for favorable RFS; insulin receptor, chemokine (C-X-C motif) receptor 2 (CXCR2), and insulin-like growth factor-1 receptor predicted for unfavorable RFS. Significant (P < 0.05) predictors for favorable OS include pAMPK, pmTOR, and EpCAM; CXCR2 and flap structure-specific endonuclease-1 predicted unfavorable OS. We have developed a comprehensive risk model predictive for recurrence in our large retrospective database, which is one of the largest reported series of resected NSCLC.

General Adherence to Guideline Recommendations on Initial Diagnosis of Bladder Cancer in the United States and Influencing Factors

BackgroundBecause international guidelines recommend best practices regarding staging of incident bladder cancer, we determined the adherence to such recommendations in the United States, performing a large retrospective database analysis. Patients and MethodsPatients with the diagnosis of urothelial cancer were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between 1992 and 2007. Staging procedures were identified and analyzed. As reference for published recommendations, we used the American Urological Association (AUA), European Association of Urology (EAU), and National Comprehensive Cancer Network (NCCN) guidelines. Based on these sources, recommended initial staging of bladder cancer was analyzed. Of all 56,130 patients, 6148 (10.9%) had a cytologic examination, 29,677 (52.9%) had a standard urinalysis, 2882 (5.1%) underwent intravenous pyelography (IVP), 6950 (12.4%) underwent retrograde pyelography (RPG), and 8145 (14.5%) had computed tomography/magnetic resonance imaging (CT/MRI). ResultsThere was a significant trend over the years to a higher use of cytologic analysis, standard urinalysis, and CT/MRI. We observed a significant trend toward a lower rate of IVP and a stable use of RPG. The limitation of our study is that claims data are designed for payment processing, not quality measurement. ConclusionDespite published recommendations on the initial diagnosis of bladder cancer, our data show that less than half of the included patients received all the elements thought to be required for an initial diagnosis of bladder cancer as recommended by guidelines. Greater adherence to recommendations may ensure optimal treatment strategies. Appropriate treatment is critical to patient outcomes, because evidence-based therapeutic management can be practiced only if an accurate assessment of the disease takes place at the time of initial diagnosis.

1764 COMPARATIVE ONCOLOGIC EFFECTIVENESS BETWEEN ROBOT-ASSISTED AND OPEN RADICAL CYSTECTOMY

1764 COMPARATIVE ONCOLOGIC EFFECTIVENESS BETWEEN ROBOT-ASSISTED AND OPEN RADICAL CYSTECTOMY

Recursive Partitioning Analysis for the Prediction of Stereotactic Radiosurgery Brain Metastases Lesion Control

The objective of this investigation was to identify independent pretreatment factors that predict for control of local brain metastases (BM) in a large single-institution series of patients receiving stereotactic radiosurgery (SRS). Recursive partitioning analysis was used to potentially identify a class of patients with durable lesion control characteristics. A retrospective SRS database containing baseline characteristics, treatment details, and follow-up data of newly diagnosed patients with 1-3 BM (on magnetic resonance imaging) treated with linear accelerator-based SRS was created. Three study endpoints were used: time to progression (primary endpoint, individual lesion progression; n = 536), time to first progression (secondary endpoint, first lesion progression on an individual patient basis; n = 380), and overall survival (secondary endpoint; n = 380). Recursive partitioning analysis (RPA) was performed to identify predictors of time to progression. Multivariable analysis demonstrated that lesion aspect/phenotype and radiotherapy schedule were independent factors associated with both progression outcomes. Presence of tumor necrosis was found to be associated with a significant hazard of progression (hazard ratio >3), whereas use of the most intense radiotherapy fractionation schedule (21 Gy in one fraction) was associated with significant reductions in progression (hazard ratio <0.3). RPA using SRS dose and lesion aspect/phenotype was created and described three distinct prognostic groups. RPA of a large retrospective database of patients receiving SRS confirmed previous observations regarding the importance of SRS dose and lesion aspect/phenotype in lesion control and overall survival. The SRS lesion analysis may help to stratify future clinical trials and better define patient care options and prognosis.

Antimicrobial therapeutic determinants of outcomes from septic shock among patients with cirrhosis

It is unclear whether practice-related aspects of antimicrobial therapy contribute to the high mortality from septic shock among patients with cirrhosis. We examined the relationship between aspects of initial empiric antimicrobial therapy and mortality in patients with cirrhosis and septic shock. This was a nested cohort study within a large retrospective database of septic shock from 28 medical centers in Canada, the United States, and Saudi Arabia by the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group between 1996 and 2008. We examined the impact of initial empiric antimicrobial therapeutic variables on the hospital mortality of patients with cirrhosis and septic shock. Among 635 patients with cirrhosis and septic shock, the hospital mortality was 75.6%. Inappropriate initial empiric antimicrobial therapy was administered in 155 (24.4%) patients. The median time to appropriate antimicrobial administration was 7.3 hours (interquartile range, 3.2-18.3 hours). The use of inappropriate initial antimicrobials was associated with increased mortality (adjusted odds ratio [aOR], 9.5; 95% confidence interval [CI], 4.3-20.7], as was the delay in appropriate antimicrobials (aOR for each 1 hour increase, 1.1; 95% CI, 1.1-1.2). Among patients with eligible bacterial septic shock, a single rather than two or more appropriate antimicrobials was used in 226 (72.9%) patients and was also associated with higher mortality (aOR, 1.8; 95% CI, 1.0-3.3). These findings were consistent across various clinically relevant subgroups. Conclusion: In patients with cirrhosis and septic shock, inappropriate and delayed appropriate initial empiric antimicrobial therapy is associated with increased mortality. Monotherapy of bacterial septic shock is also associated with increased mortality. The process of selection and implementation of empiric antimicrobial therapy in this high-risk group should be restructured. (Hepatology 2012;56:2305–2315)

Abstract 18820: Estimating Time In Therapeutic Range Using The Percentage of Visits in International Normalized Ratio Range Among Patients with Nonvalvular Atrial Fibrillation

OBJECTIVES: Time in therapeutic range (TTR) has been a quality indicator for level of anticoagulation even though it is not readily available for practitioners to estimate level of anticoagulation for patients. A simpler measure that is based on the number of visits, percentage of visits in international normalized ratio (INR) range (PVIR), may estimate the anticoagulant control. This measure is examined for correlation with TTR levels achieved among patients with nonvalvular atrial fibrillation (NVAF) in a large retrospective database. METHODS: We analyzed longitudinal patient-level anticoagulation management records collected between 2006 and 2010 by decision support software, CoagClinic™. Adult patients with NVAF with at least 2 anticoagulation clinic visits and no gap &gt;180 days between visits were identified. The Rosendaal method was used to calculate TTR. Anticoagulation visits with 2.0≤ INR≤3.0 was defined as visits within INR range. PVIR was calculated by dividing the number of visits within INR range by the total number of visits. PVIR was stratified by the increment of 10%, and then compared to corresponding TTR. Pearson correlation coefficient between TTR and PVIR was calculated. RESULTS: We identified 36,978 patients who met all inclusion criteria. The mean (±SD) age was 72.3±10.6 years, with 78.4% ≥65 years. The mean (±SD) TTR was 62.2±20.7. On average, patients had 39 visits, of which 23 were in INR range. The average PVIR was 59%. A substantial proportion of patients (79%) had PVIR ≤70%; 18% of patients had PVIR between ≤71% and ≤90%; only about 3% had PVIR ≥91%. PVIR and TTR showed a strong linear relationship (Table 1; Pearson correlation coefficient=0.87). CONCLUSIONS: Percentage of visits in INR range (PVIR) offers a simplified measure for daily practitioners to estimate level of anticoagulation control and help identify patients with poor control.

Benefit of an early and systematic imaging procedure after cardiac arrest: Insights from the PROCAT (Parisian Region Out of Hospital Cardiac Arrest) registry

AimsIdentification of the cause of out-of-hospital cardiac arrest (OHCA) is of paramount importance. We investigated the ability of our imaging strategy to provide an early etiological diagnosis of OHCA and the influence of this strategy on ICU survival. MethodsRetrospective review of a prospectively acquired ICU database (01/2000–12/2010) including all OHCA patients without obvious extracardiac cause, for which an early diagnosis research was conducted (coronary angiography and/or brain and chest CT scan) within 24h after resuscitation. These procedures could be performed separately or be combined, according to a decision algorithm. ResultsOf the 1274 patients admitted after OHCA during this 10-year period, the imaging strategy was applied in 896 patients. Patients who benefited from coronary angiography and/or CT scan were admitted to our ICU after a median delay of 180 [130–220]min after resuscitation. Seven hundred and forty-five coronary angiographies were performed, of which 452 (61%) identified at least one significant coronary lesion deemed responsible for the OHCA. CT-scan was performed in 355 patients and provided a diagnosis in 72 patients (20%), mainly stroke (n=38) and pulmonary embolism (n=19). Overall, this strategy allowed early diagnosis in 524 patients (59%). ICU survival was significantly higher for patients with a diagnosis identified by coronary angiography as compared with CT-scan (43% vs 10%, p<0.001). ConclusionThe use of an early diagnosis protocol with immediate coronary angiography and/or CT scan provided the etiology of nearly two thirds of OHCA cases. In this large retrospective database, coronary angiography yielded a better diagnostic value than brain and/or chest CT-scan.

The economic burden of pleural effusions in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors

Objective:Tyrosine kinase inhibitors (TKI), the standard of care for patients with chronic myeloid leukemia (CML) patients, may in some cases lead to the development of pleural effusion (PE). The purpose of this study is to compare healthcare resource utilization and costs associated with PE among CML patients treated with a TKI therapy.Methods:Two large retrospective claims databases (1999–2009) were combined to identify adult CML patients who received ≥1 TKI prescription before the index date, which was defined as 30 days before the first PE diagnosis for patients with PE and a randomly selected date for PE-free patients. Patients were followed for 6 months after the index date. PE and PE-free patients were matched on a 1:1 ratio. PE-related resource utilization and costs (measured in 2009 US dollars) were estimated for PE patients. All-cause and CML-related resource utilization and costs were compared between PE and PE-free patients. Multivariate regression models were used to control for confounding factors.Results:The study included 186 matched pairs. PE-free and PE patients were on average 65.4 and 63.6 years old and 39.8% and 48.9% were female, respectively. PE patients had a significantly higher number of inpatient (IP) days, IP admissions, outpatient (OP) visits and emergency room (ER) visits than PE-free patients (all p < 0.01). All-cause medical services costs were $88,526 and $30,434 for PE and PE-free patients, respectively. After adjusting for confounding factors, the PE-related total medical costs were $47,288 (p < 0.01), which was mostly accounted for by higher IP (difference: $34,123, p < 0.01) and OP (difference: $9563, p < 0.05) costs. PE patients also incurred higher CML-related medical costs compared to PE-free patients (difference: $39,599; p < 0.01).Conclusion:PE presents a substantial economic burden for CML patients treated with TKI.

Biologic risk model for recurrence in resected early-stage non-small cell lung cancer (ES NSCLC).

7053 Background: Patients (pts) with resected ES NSCLC are at risk for recurrence of disease and mortality but we do not have tools to predict which pts are at highest risk. Risk models have been proposed but have not included predictive biomarkers for recurrence. Methods: We assembled a large comprehensive database with archival tissues and clinical follow-up from pts with resected ES NSCLC between 2002-2005. 21 biomarkers identified from our preclinical studies as related to pathogenesis of NSCLC were investigated, including pathways related to apoptosis, metabolism, DNA repair, inflammation and growth factors. Tissue microarrays were constructed from archived specimens. Cox models were fitted to estimate effects of clinical factors and biomarkers on recurrence free survival (RFS) and overall survival (OS). Predictive accuracy was quantified by C-index. Results: 370 pts are included in our analysis, 50.3% (186 pts) male, 89% (330) white. Smoking status: 44% (162) current, 46% (170) former, 10% (38) never. Stage IA 28% (103), IB 35% (131), II 20% (75), IIIA 17% (61). Adenocarcinoma 61% (227), squamous 34% (126). 45% (160) received chemotherapy or radiation as well as surgery. With median follow-up of 5.3 yrs, median OS is 6.4 yrs. 209 cases with recurrence or death were observed. The biologic risk model included relevant biomarkers, age and stage. See table for significant (p<.05) predictive markers after adjusting for age and stage. C-index is 0.66 for both models indicating adequate prediction accuracy. Conclusions: We have developed a biologic risk model predictive for recurrence in our large retrospective database. This is the first report of a risk model incorporating biomarkers and will be validated in our ongoing prospective study. DoD W81XWH-04-1-0142, NCIP01 91844. Hazard ratio RFS Hazard ratio OS Pathway Negative cytoplasmic(c-) pAMPK 1.54 1.49 Metabolism Positive membrane (m-) insulin receptor 1.44 n/a Proliferation Negative c-EpCAM 1.41 1.54 Differentiation Negative c- pmTOR 1.44 1.51 Metabolism High c-CXCR2 1.36 1.57 Inflammation High c- IGF1R (continuous variable) 1.004 n/a Proliferation Low m-CASK (continuous variable) 1.004 n/a Extracellular matrix interaction High nuclear FEN1 n/a 1.42 DNA repair

Retrospective real-world comparison of medical visits, costs, and adherence between nilotinib and dasatinib in chronic myeloid leukemia

Objective:To compare healthcare resource utilization, costs, and treatment adherence associated with dasatinib versus nilotinib treatment as second-line therapies in chronic myeloid leukemia (CML) patients.Methods:Two large retrospective claims databases (01/1999–06/2009) were combined to identify CML patients (ICD-9 code 205.1x) who received one or more prescriptions of dasatinib or nilotinib. Studied patients had continuous enrollment ≥1 month prior to and after the index date, defined as the first prescription for dasatinib or nilotinib. Patients were followed for up to 6 months from the index date to the earliest of the termination of healthcare plan enrollment or end of data availability. Patients with bone marrow or stem cell transplant during the study period were excluded. Poisson regression models were used to compare healthcare resource utilization between the two groups. Results were reported as incidence rate ratios (IRR). Healthcare cost differences were estimated for each cost component using generalized linear models or two-part models. Treatment adherence was measured by the proportion of days covered (PDC) and compared using generalized linear models. Multivariate regressions were used to control for potential confounding factors.Results:A total of 521 CML patients receiving second-line tyrosine kinase inhibitors (TKI) (452 dasatinib and 69 nilotinib) were studied. During the study period, dasatinib patients were estimated to have more than twice as many inpatient days (IRR = 2.44; p < 0.001) and nearly double the number of inpatient admissions (IRR = 1.99; p = 0.047) compared to nilotinib patients. Over the follow-up period, dasatinib patients incurred $8828 more in total medical service costs (p < 0.001); cost differences were mainly driven by an adjusted inpatient cost difference of $8520 (p = 0.003). Dasatinib patients were less adherent, with a PDC value approximately 13% lower compared to nilotinib patients (p = 0.009).Conclusions:Among CML patients treated with second-line TKIs, nilotinib patients were more adherent and experienced lower healthcare resource utilization, resulting in medical service cost savings compared to dasatinib patients.

The Impact of Morbid Obesity and Bariatric Surgery on Comorbid Conditions: A Comprehensive Examination of Comorbidities in an Employed Population

Find conditions with significantly different prevalence among employees diagnosed with morbid obesity (DMO). Examine the effect of bariatric surgery on the prevalence of all categories of comorbid conditions after surgery. This large employer retrospective database analysis used matching to create two cohorts: Those with a DMO and those without. The DMO cohort had higher diagnosis rates in every Agency for Healthcare Research and Quality major diagnostic category except pregnancy, and it had significantly higher prevalence in 147 of 261 Agency for Health care Research and Quality specific categories. Those electing to undergo bariatric surgery experienced significant prevalence decreases in 26 of 261 specific categories. Employees DMO are at higher risk for many serious diseases. Bariatric surgery has been effective in promoting weight loss and decreasing the rates of many serious comorbidities.

The Association of Insulin Medication Possession Ratio, Use of Insulin Glargine, and Health Benefit Costs in Employees and Spouses With Type 2 Diabetes

Measure the impact of insulin utilization on health costs and absenteeism. Compare outcomes between users of insulin glargine and other insulin. Using a large retrospective database, this regression analysis examined annual health costs and absenteeism among employees and spouses with type 2 diabetes who used insulin. The analysis studied impacts of medication possession ratio (MPR) and glargine use, controlling for demographic factors, salary, and prior health care. Higher MPR was associated with significantly lower health costs for patients with high prior costs. Glargine users' MPR was higher than other insulin users' MPR (66% vs 54%, P < 0.0001). Among all insulin users, those using glargine had significantly lower total ($6771 vs $7969, P = 0.0046) and circulatory-specific ($312 vs $636, P < 0.0001) costs. Insulin MPR and the use of insulin glargine were associated with lower health care costs.

Stochastic modelling of genotypic drug-resistance for human immunodeficiency virus towards long-term combination therapy optimization

Several mathematical models have been investigated for the description of viral dynamics in the human body: HIV-1 infection is a particular and interesting scenario, because the virus attacks cells of the immune system that have a role in the antibody production and its high mutation rate permits to escape both the immune response and, in some cases, the drug pressure. The viral genetic evolution is intrinsically a stochastic process, eventually driven by the drug pressure, dependent on the drug combinations and concentration: in this article the viral genotypic drug resistance onset is the main focus addressed. The theoretical basis is the modelling of HIV-1 population dynamics as a predator-prey system of differential equations with a time-dependent therapy efficacy term, while the viral genome mutation evolution follows a Poisson distribution. The instant probabilities of drug resistance are estimated by means of functions trained from in vitro phenotypes, with a roulette-wheel-based mechanisms of resistant selection. Simulations have been designed for treatments made of one and two drugs as well as for combination antiretroviral therapies. The effect of limited adherence to therapy was also analyzed. Sequential treatment change episodes were also exploited with the aim to evaluate optimal synoptic treatment scenarios. The stochastic predator-prey modelling usefully predicted long-term virologic outcomes of evolved HIV-1 strains for selected antiretroviral therapy combinations. For a set of widely used combination therapies, results were consistent with findings reported in literature and with estimates coming from analysis on a large retrospective data base (EuResist).