Costs of Newborn Care Following Complications During Pregnancy and Delivery.

The aim of this study is examine the impact of pregnancy and delivery complications on the healthcare costs of newborns during the first 3 months of life. We conducted a retrospective cohort study of newborns born to women ages 15-49 using de-identified medical and pharmacy claims from the Truven Health MarketScan Commercial Claims and Encounters database incurred between January 1, 2007 and December 31, 2011. Total healthcare costs and resource utilization were examined and compared for the first 3 months of life between cohorts of newborns either with or without evidence of categorized maternal complications. Incremental costs were also determined using multivariable analysis for the conditions found to be the most prevalent in the study population. A total of 137,040 infants were studied, 75.4% of which were born to mothers who had experienced at least one complication during pregnancy or delivery. Fetal abnormalities (26.2%), early or threatened labor (16.6%), and hemorrhage (10.8%) were the most frequently observed complications. Diabetes (8.0%) and hypertension (7.7%) were also common, with the majority of other conditions present in 1% or less of the study population. Adjusted analyses found significant differences for seven conditions where incremental costs ranged from $987 to $10,287. Complications are common during pregnancy and delivery and some complications may lead to increased healthcare costs for newborns immediately following birth.

Inflammation plays a causal role in fatigue-like behavior induced by pelvic irradiation in mice.

Fatigue is a persistent and debilitating symptom following radiation therapy for prostate cancer. However, it is not well-understood how radiation targeted to a small region of the body can lead to broad changes in behavior. In this study, we used targeted pelvic irradiation of healthy male mice to test whether inflammatory signaling mediates changes in voluntary physical activity levels. First, we tested the relationship between radiation dose, blood cell counts, and fatigue-like behavior measured as voluntary wheel-running activity. Next, we used oral minocycline treatments to reduce inflammation and found that minocycline reduces, but does not eliminate, the fatigue-like behavioral changes induced by radiation. We also used a strain of mice lacking the MyD88 adaptor protein and found that these mice also showed less fatigue-like behavior than the wild-type controls. Finally, using serum and brain tissue samples, we determined changes in inflammatory signaling induced by irradiation in wild-type, minocycline treated, and MyD88 knockout mice. We found that irradiation increased serum levels of IL-6, a change that was partially reversed in mice treated with minocycline or lacking MyD88. Overall, our results suggest that inflammation plays a causal role in radiation-induced fatigue and that IL-6 may be an important mediator.

Development of a mouse model of induced Staphylococcus aureus infective endocarditis.

We developed a mouse model of Staphylococcus aureus infective endocarditis to evaluate the efficacy of experimental antibacterial compounds for this disease. Experimental infective endocarditis was produced in CD1 mice by intravenous challenge with approximately 6 log10 colony-forming units (CFU) of methicillin-sensitive (MSSA) SA-3529 or -resistant (MRSA) SA-2015 S. aureus 1 d after aortic valve trauma. Valve trauma was produced by introduction of an indwelling 32-gauge polyurethane catheter into the aortic valve via the left carotid artery. Histologic examination of MSSA- and MRSA-infected and catheterized aortic valve sections revealed neutrophilic inflammation and vegetative bacterial colonies encapsulated within fibrin along the aortic valves 1 d after infection. The MSSA or MRSA endocarditis was determined to be catheter-dependent based on catheterized mice exhibiting heart bacterial counts 4 orders of magnitude greater than those seen for noncatheterized mice. The model was validated by using a 3-d regimen of vancomycin at exposures comparable to human dosing (500 microg x h/ml). Vancomycin treatment produced statistically significant reductions of 3.4 and 3.1 log10 CFU/heart for MSSA and MRSA, respectively, relative to controls. This mouse model of endocarditis shows promise in evaluating the predictive efficacy of antibiotics for S. aureus infective endocarditis.

The Additional Cost Burden of Preexisting Medical Conditions During Pregnancy and Childbirth.

OBJECTIVES: To identify the prevalence of comorbidities in pregnant women and examine the incremental costs of these conditions on the care for mothers and their newborns. METHODS: This was a retrospective comparative cohort study of women ages 15-49 years with a documented live-birth delivery using de-identified claims from the MarketScan Research Commercial Claims and Encounters database incurred between January 1, 2007, and December 31, 2011. Total health care costs from date of first pregnancy-related claim through 3 months postdelivery were reported; pregnancy-related comorbidities prior to the pregnancy diagnosis were identified and categorized in the 12 months prior to the pregnancy diagnosis, and costs associated with each condition were compiled. A subset of newborns was matched to their mothers using a unique family identifier and their costs were captured for the three months following birth. Comparisons of costs for both mothers and newborns were made using both unadjusted and multivariate analyses between mothers with and without each condition. RESULTS: A total of 322,141 women with live births were identified; 135,572 of these mothers were linked to their newborn(s). Prevalent conditions included back disorders (8.9%), mental disorders (6.5%), headache (5.5%), allergic rhinitis (5.5%), and osteoarthritis (4.8%). Diabetes (0.97%) and hypertension (1.9%) were associated with the highest adjusted incremental costs of care in both mothers ($6,211 [95% confidence interval 5,720-6,702] and $3,367 [95% CI 2,935-3,799] respectively) and newborns ($2,067 [95% CI 1,515-2618]; and $1,210 [95% CI 725-1,695] respectively). The two most common conditions, back disorders and mental disorders, were associated with unadjusted costs of $1,895/$978 (mothers/infants) and $2,097/$1,902 (mothers/infants) respectively. CONCLUSION: Preexisting conditions common in pregnant women may result in additional resource utilization and costs for both mothers and newborns.

Persistance and Compliance with Osteroporosis Therapies Among Women in a Commercially Insured Population in the United States.

BACKGROUND: Prior research has shown that rates of persistence and compliance with osteoporosis therapies are associated with significantly fewer vertebral, nonvertebral, and hip fractures. A number of studies have examined medication-taking behavior with oral bisphosphonates and teriparatide, and these 1-year persistence rates have ranged from 39.9% to 56.7%. Limited real-world data are available regarding persistence and compliance rates with newer therapies such as denosumab, a RANK ligand inhibitor administered every 6 months as a subcutaneous injection.  OBJECTIVE: To assess persistence and compliance rates over 1 year with newly initiated osteoporosis therapies, including denosumab, alendronate, ibandronate, risedronate, raloxifene, and teriparatide, within a cohort of commercially insured women.  METHODS: Health insurance claims data derived from Truven Health Analytics MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases (2010-2013) were used to conduct this retrospective cohort study. Adult females aged 18 years and older newly initiated on denosumab, raloxifene, teriparatide, or oral bisphosphonates (alendronate, ibandronate, or risedronate) between January 1, 2012, and March 31, 2012, were identified for inclusion. The date of the first qualifying osteoporosis prescription claim was defined as the index date. Patients were required to have at least 24 months of pre-index and at least 12 months of post-index continuous enrollment with medical and pharmacy benefits. Outcomes of patients initiating zoledronic acid (administered intravenously once yearly) were not assessed because a 12-month follow-up period would be insufficient for tracking persistence and compliance for this medication. Patients with Paget's disease of the bone, osteogenesis imperfecta, hypercalcemia, malignant cancer and metastasis, human immunodeficiency virus, and patients receiving preventive treatment for risk of breast cancer or denosumab in the pre-index period were excluded from the study. A subcohort of women aged 50 years and older at high risk for fracture (indicated by 1 or more of the following: aged ≥ 70 years, a pre-index fracture, or pre-index use of osteoporosis therapy that was discontinued at least 3 months prior to index) was analyzed separately. Propensity score weighting was used to adjust for differences in baseline demographic and clinical characteristics. Persistence, indicated by continuous use of the index therapy without a gap of 60 days or more; medication coverage ratio (MCR), the proportion of days covered by the index therapy; and compliance, defined as an MCR ≥ 0.80, were assessed during the 12-month follow-up. Logistic regression was used to estimate the odds of persistence and compliance for the treatment groups of interest. RESULTS: 10,863 female patients newly initiating osteoporosis medications (mean [SD] age: 66.2 [11.5] years) were identified. In the pre-index period, 35.8% of patients had a diagnosis of osteoporosis, while 11.5% had a diagnosis of osteopenia. Pre-index osteoporosis treatment was identified in 29.1% of patients, and 13.6% had an osteoporosis-related fracture in the pre-index period. Propensity score weight-adjusted 12-month persistence with the index medication varied from 28.9% to 35.1% for oral bisphosphonate users, 42.0% for raloxifene users, 59.1% for teriparatide users, and 68.3% for denosumab users (P less than 0.0001). The adjusted mean [SD] MCR was highest among patients treated with denosumab (0.83 [0.21]), followed by teriparatide (0.67 [0.31]), raloxifene, (0.57 [0.34]), ibandronate (0.54 [0.32]), alendronate (0.51 [0.33]), and risedronate (0.46 [0.33]; P less than 0.0001). The odds of being persistent and compliant across treatments favored denosumab (OR = 1.59 to 5.56, P less than 0.05 for persistence; OR = 2.44 to 7.69, P less than 0.0001 for compliance). Results were similar in the subcohort of women aged 50 years and older at high risk for fracture (n = 6,187; mean [SD] age: 71.9 [10.9] years). The odds of being persistent and compliant across treatments also favored denosumab (OR = 1.62 to 5.75, P less than 0.0001 for persistence; OR = 2.36 to 7.25, P less than 0.0001 for compliance). CONCLUSIONS: In a U.S. setting, rates of persistence and compliance over 12 months were higher among women initiating denosumab compared with those initiating other osteoporosis therapies.

The prevalence of complications and healthcare costs during pregnancy.

OBJECTIVE: To study the economic burden of pregnancy in the US, common complications during pregnancy, and the incremental costs attributable to these complications. METHODS: A retrospective comparative cohort study was conducted of pregnant women aged 15-49 years using de-identified medical and pharmacy claims from the Truven Health MarketScan Commercial Claims and Encounters database incurred between January 1, 2007 and December 31, 2011. The total healthcare costs are reported (adjusted to 2011 dollars) from the date of the first pregnancy-related claim through to 3 months post-delivery and these costs were compared to matched controls of non-pregnant women. Pregnancy-related complications were categorized, and the incremental costs associated with each complication were estimated using multivariate analyses. RESULTS: A total of 322,141 eligible women with live births were studied. Compared to matched controls, the average costs of care for pregnant women were nearly $13,000 higher through 3 months post-delivery. A total of 46.9% of women had at least one pre-specified pregnancy complication; the most commonly observed were fetal abnormality (24.7%) and early or threatened labor (16.3%). Multiple gestation (1.9%) resulted in the highest adjusted incremental cost ($12,212; 95% CI = 11,298, 13,216); hypertension ($6152; 95% CI = 5312, 6992) and diabetes ($5081; 95% CI = 4244, 5918) were also among those complications that led to high incremental costs of care. CONCLUSION: Pregnancy and delivery are frequently compounded by complications that lead to increased costs and resource utilization.

Predictors of medication adherence in patients with type 2 diabetes mellitus.

OBJECTIVE: Medical professionals are often challenged by lack of patient compliance with pharmaceutical treatments. Research has shown that patients with diabetes have one of the lowest medication adherence rates at 65% to 85%. Some causes have been identified in the literature, but the influence of type of medication is unknown. This study assessed the impact of a broad range of factors on medication adherence and persistence among adult patients with type 2 diabetes mellitus. METHODS: Patients were selected from the Truven Health MarketScan Research Databases of healthcare administrative claims (2009 through 2012), assigned to mutually exclusive cohorts based on initiation of saxagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor), or a glucagon-like peptide 1 (GLP-1) receptor agonist (daily or twice daily formulation), sulfonylurea (SU), or thiazolidinedione (TZD), and screened for continuous enrollment 1 year before and after drug initiation. Adherence and persistence were measured using proportion of days covered and time to discontinuation, respectively. Multivariate models were used to examine the impact of study drug and demographic and clinical factors. RESULTS: Overall, 45.1% of patients were adherent with their study drug over the 1 year follow-up period. Adherence was higher among patients who were male, older, or residing in non-Southern states. Adherence was better with mail-order use and lower levels of cost sharing. Patients taking a GLP-1 (OR = 0.40, 95% CI = 0.37, 0.42), SU (OR = 0.49, 95% CI = 0.46, 0.52), or TZD (OR = 0.54, 95% CI = 0.51, 0.57) were less likely to be adherent compared with those taking saxagliptin. Results were mixed regarding the impact of comorbidities and polypharmacy on medication adherence. Influencing factors may be the type of comorbidity, overall health level, number of drugs, and complexity of the drug regimen. KEY LIMITATIONS: Adherence was measured using data for prescriptions dispensed and it is not known whether patients actually took the medications, hence adherence may be overestimated. Whether patients who discontinued the study drugs switched to other diabetes medications or discontinued treatment completely was not measured. CONCLUSION: Identified risk factors can guide medical professionals in their attempts to increase the likelihood of patient adherence to drug treatment regimens.

Assessment of ex vivo pharmacodynamic markers during inhibition of thrombosis by CI-1031 (ZK-807834), a novel direct factor Xa inhibitor.

CI-1031 (ZK-807834) is a novel, synthetic factor Xa (FXa) inhibitor with a Ki of 0.11 nM against human FXa. In human plasma in vitro, CI-1031 doubled PT and aPTT at 0.23 and 0.49 microM, respectively. The in vivo antithrombotic effect of CI-1031 was evaluated in a veno-venous shunt model of thrombosis in anesthetized rabbits. After thrombus formation was verified in the first shunts, rabbits received either vehicle or CI-1031 intravenously (bolus injection of 60, 240, or 480 microg/kg followed by an infusion of 2, 8, or 16 microg/kg/min for 140 min, respectively). The second shunts were inserted after 20 min of infusion of CI-1031 or vehicle. CI-1031 dose-dependently prolonged time to occlusion (TTO) in the second shunts (35 +/- 21, 62 +/- 24, and 120 +/- 0 min for the three dose groups, respectively, vs. 10 +/- 1 min for vehicle). Thrombus mass (TM) was reduced in a dose-dependent manner by CI-1031 (42 +/- 7, 27 +/- 6, and 18 +/- 4 mg vs. 50 +/- 4 mg for vehicle). Maximal TM reduction was 70% with an IC(50) of 0.6 microg/ml. Among all the coagulation parameters tested, PT had the best correlation with plasma CI- 1031 concentration (r = 0.97). Ex vivo plasma anti-FXa activity was also well correlated with plasma concentration of CI-1031 and with PT (r = 0.96 and 0.98, respectively). These results indicate that CI-1031, which is currently undergoing clinical evaluation, is an effective antithrombotic compound with a favorable efficacy-to-bleeding ratio. In addition, CI-1031 concentration in plasma can be monitored using PT or anti-Xa assays, thereby providing reliable methods to ensure safe and accurate dose titration of CI-1031.