Utilization and Adherence Patterns of Subcutaneously Administered Anti–Tumor Necrosis Factor Treatment Among Rheumatoid Arthritis Patients

AbstractBackgroundAdherence to therapy is a key requirement underlying achievement of clinical outcomes in randomized controlled drug registration trials. In postmarketing studies, comparison of adherence among therapies can become more complicated when drug dosing and administration schedules differ or when methods used to measure adherence are not consistently applied.ObjectiveThe objective of this exploratory study was to investigate a broad range of utilization and adherence outcomes associated with subcutaneous biologic treatments for rheumatoid arthritis (RA).MethodsAdult patients (aged ≥18 years) exhibiting ≥2 claims with an RA diagnosis (code 714.x), at least 24 months of continuous medical and pharmacy eligibility, and 30-day supplies of adalimumab, etanercept, or golimumab were selected from the Optum Insight Clinformatics database. Adherence and utilization measures were calculated and compared across treatment groups.ResultsA total of 1532 adalimumab, 2099 etanercept, and 261 golimumab patients met inclusion criteria. Compared with both adalimumab and etanercept patients, golimumab patients were significantly more likely to have a medication possession ratio of ≥0.80 (82% vs 71% vs 62%; P < 0.001) and significantly less likely to have ≥4 late medication refills (6.9% vs 17.7% vs 26.1%; P < 0.001 for all). Etanercept patients had significantly greater refill intervals (37.7 vs 34.9 and 35.1 days) and had the lowest proportion of adherent fills (70% vs 77% and 75%) compared with both golimumab and adalimumab patients (P < 0.001 for all). Bivariate effects were reproduced in multivariate models that controlled for treatment duration.ConclusionsA number of statistically significant medication adherence differences were observed among golimumab, adalimumab, and etanercept patients in treatment for RA. Overall, golimumab patients appeared to be the most adherent group. Findings may be partially attributable to golimumab patients’ likely increased disease severity, their prior experience with biologic medication, or golimumab’s once-monthly dosing schedule, which requires fewer administrations than both adalimumab and etanercept

Differential Cerebral Cortex Transcriptomes of Baboon Neonates Consuming Moderate and High Docosahexaenoic Acid Formulas

BACKGROUND: Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (ARA, 20:4n-6) are the major long chain polyunsaturated fatty acids (LCPUFA) of the central nervous system (CNS). These nutrients are present in most infant formulas at modest levels, intended to support visual and neural development. There are no investigations in primates of the biological consequences of dietary DHA at levels above those present in formulas but within normal breastmilk levels. METHODS AND FINDINGS: Twelve baboons were divided into three formula groups: Control, with no DHA-ARA; “L”, LCPUFA, with 0.33%DHA-0.67%ARA; “L3”, LCPUFA, with 1.00%DHA-0.67%ARA. All the samples are from the precentral gyrus of cerebral cortex brain regions. At 12 weeks of age, changes in gene expression were detected in 1,108 of 54,000 probe sets (2.05%), with most showing <2-fold change. Gene ontology analysis assigns them to diverse biological functions, notably lipid metabolism and transport, G-protein and signal transduction, development, visual perception, cytoskeleton, peptidases, stress response, transcription regulation, and 400 transcripts having no defined function. PLA2G6, a phospholipase recently associated with infantile neuroaxonal dystrophy, was downregulated in both LCPUFA groups. ELOVL5, a PUFA elongase, was the only LCPUFA biosynthetic enzyme that was differentially expressed. Mitochondrial fatty acid carrier, CPT2, was among several genes associated with mitochondrial fatty acid oxidation to be downregulated by high DHA, while the mitochondrial proton carrier, UCP2, was upregulated. TIMM8A, also known as deafness/dystonia peptide 1, was among several differentially expressed neural development genes. LUM and TIMP3, associated with corneal structure and age-related macular degeneration, respectively, were among visual perception genes influenced by LCPUFA. TIA1, a silencer of COX2 gene translation, is upregulated by high DHA. Ingenuity pathway analysis identified a highly significant nervous system network, with epidermal growth factor receptor (EGFR) as the outstanding interaction partner. CONCLUSIONS: These data indicate that LCPUFA concentrations within the normal range of human breastmilk induce global changes in gene expression across a wide array of processes, in addition to changes in visual and neural function normally associated with formula LCPUFA

TCRβ Feedback Signals Inhibit the Coupling of Recombinationally Accessible Vβ14 Segments with DJβ Complexes

Ag receptor allelic exclusion is thought to occur through monoallelic initiation and subsequent feedback inhibition of recombinational accessibility. However, our previous analysis of mice containing a V(D)J recombination reporter inserted into Vβ14 (Vβ14[superscript Rep]) indicated that Vβ14 chromatin accessibility is biallelic. To determine whether Vβ14 recombinational accessibility is subject to feedback inhibition, we analyzed TCRβ rearrangements in Vβ14[superscript Rep] mice containing a preassembled in-frame transgenic Vβ8.2Dβ1Jβ1.1 or an endogenous Vβ14Dβ1Jβ1.4 rearrangement on the homologous chromosome. Expression of either preassembled VβDJβC β-chain accelerated thymocyte development because of enhanced cellular selection, demonstrating that the rate-limiting step in early αβ T cell development is the assembly of an in-frame VβDJβ rearrangement. Expression of these preassembled VβDJβ rearrangements inhibited endogenous Vβ14-to-DJβ rearrangements as expected. However, in contrast to results predicted by the accepted model of TCRβ feedback inhibition, we found that expression of these preassembled TCR β-chains did not downregulate recombinational accessibility of Vβ14 chromatin. Our findings suggest that TCRβ-mediated feedback inhibition of Vβ14 rearrangements depends on inherent properties of Vβ14, Dβ, and Jβ recombination signal sequences

Intra-Operative Anastomotic Leak Rates and Testing Methodology in Colorectal Resection Surgery

Purpose: Anastomotic leak following colorectal resection surgery is associated with high rates of morbidity, infection, and escalated healthcare expenditures. One method to prevent leaks includes early detection through intra-operative testing. This study employed systematic review of the literature to estimate the rate of intra-operative anastomotic leaks in colorectal resection surgery.Method: The Medline and Embase databases were searched to identify articles published between January 1st, 2003 and August 8th, 2015 reporting on intra-operative leaks in colorectal resection. The rate of intra-operative testing, intra- and post-operative anastomotic leaks, and surgical methodology were extracted from the final sample of 13 articles.Results: A total of 167 intra-operative leaks were reported within 2,598 colorectal resection surgeries that used intra-operative testing, yielding an average leak rate of 6.4%. Use of laparoscopic techniques was significantly associated with a reduced rate of intra-operative leak (p&lt;0.001). Eight articles reported on the rate of post-operative anastomotic leak in relation to intra-operative testing. Within this sample of 2,098 cases a non-significant trend towards a lower leak rate in the tested population was identified (4.3% v. 6.8%, p=0.051); cases whose leak test was initially positive exhibited a significantly higher rate of post-operative leaks compared to cases with a negative leak test (p=0.006).Conclusion: Intra-operative anastomotic leak testing allows surgeons to address leaks at the time of surgery, and may help to prevent complications in colorectal resection surgery. This study identified a mean intra-operative leak rate of 6.4% in colorectal resection surgery.</p

Estimated Rate of Post-Operative Anastomotic Leak Following Colorectal Resection Surgery: A Systematic Review

Purpose: Anastomotic leak following colorectal resection surgery is associated with short and long-term negative patient outcomes, prolonged hospitalization, and increased healthcare costs. Various patient related and surgical factors are known to contribute to the development of postoperative anastomotic leaks. This study systematically reviewed the literature to assess the incidence of post-operative leak and identify patient factors associated with the development of leaks.Methods: Articles published from 1/1/2003 – 8/8/2015 reporting on post-operative anastomotic leak following colorectal resection surgery were identified in the Medline and Embase databases. The rate of post-operative leak, as well as patient and surgical characteristics, were extracted.Results: Forty-three articles met study inclusion criteria. Within the 14,102 cases, 867 patients experienced anastomotic leak, yielding an average leak rate of 6.1%. Patients were primarily male (57.0%) and had a mean age of 60.2 years. The majority of patients received a stapled anastomosis (70.9%), and most resection surgeries were performed for a diagnosis of cancer (80.7%). Comparison of patient characteristics with and without a post-operative leak revealed male gender, diabetes, open surgical procedures, and sutured anastomoses to be risk factors of anastomotic leak. Patients with anastomotic leak had a longer length of stay in the hospital and higher mortality rate than patients without a leak.Conclusions: Anastomotic leak remains a major concern in colorectal resection surgery and occurs in approximately 6.1% of cases. Both patient and surgical factors are associated with the development of post-operative anastomotic leak, which is linked to negative patient outcomes and increased mortality.</p

Diagnosis and management of a heterotopic pregnancy and ruptured rudimentary uterine horn

Abstract Background Heterotopic pregnancies implanted in a rudimentary uterine horn account for 1 in 2–3 million gestations, and confer significant risk of morbidity due to uterine rupture and hemorrhage. Case presentation A 34-year-old nullipara presented with acute pelvic pain at 17 weeks of gestation with dichorionic-diamniotic twins, one in each horn of an anomalous uterus first diagnosed in pregnancy as bicornuate. Three-dimensional ultrasound and MRI revealed myometrial disruption in the left rudimentary uterine horn, and the patient underwent an uncomplicated abdominal hemi-hysterectomy. Fourteen days later, an uncomplicated dilation and curettage was performed for a fetal anomaly in the remaining twin in the right unicornuate uterus. Conclusion This case demonstrates the utility of magnetic resonance imaging and three-dimensional ultrasound in the assessment of myometrial integrity in a gravid patient with a heterotopic pregnancy and ruptured rudimentary uterine horn. This case demonstrates the importance of pre-pregnancy diagnosis and management of mullerian anomalies