Economic Evaluation of Tocilizumab Monotherapy Compared to Adalimumab Monotherapy in the Treatment of Severe Active Rheumatoid Arthritis

AbstractObjectivesTo estimate the cost-effectiveness of tocilizumab (TCZ) monotherapy (Mono) versus adalimumab (ADA) Mono from the US payer perspective in patients with rheumatoid arthritis for whom methotrexate is inappropriate.MethodsWe compared TCZ Mono (8 mg/kg monthly) with ADA Mono (40 mg every other week), using efficacy results from a head-to-head study, ADalimumab ACTemrA (ADACTA). We calculated the incremental cost per responder (achievement of American College of Rheumatology [ACR] 20% improvement criteria, ACR 50% improvement criteria, ACR 70% improvement criteria, or low disease activity score) for TCZ versus ADA at 6 months. A patient-level simulation was used to estimate the lifetime incremental cost per quality-adjusted life-year (QALY) of initiating treatment with TCZ Mono versus ADA Mono. Both drugs are followed by an etanercept-certolizumab-palliative care sequence. Nonresponders discontinue at 6 months; responders experience a constant probability of discontinuation. Discontinuers move to the next treatment. ACR responses produce changes in the Health Assessment Questionnaire (HAQ) score. We mapped the HAQ score to utility to estimate QALYs. Costs include those related to hospitalization and those related to treatment (drug acquisition, administration, and monitoring). Probabilistic and one-way sensitivity analyses were conducted, along with several scenario analyses.ResultsCompared with ADA, TCZ was more effective, with an estimated 6-month incremental cost ranging from $6,570 per additional low disease activity score achiever to$14,265 per additional ACR 70% improvement criteria responder. The lifetime incremental cost-effectiveness ratio was $36,944/QALY.ConclusionsTCZ Mono is projected to be cost-effective compared with ADA Mono in patients with severe rheumatoid arthritis for whom methotrexate is not appropriate, from a US payer perspective

Building a Bicycle-Powered Centrifuge

Centrifuges are very common instruments utilized in research and clinical settings. The purpose of a centrifuge is to separate the components of a mixture using centrifugal force. An example of a process that utilizes centrifugation is the acquisition of a hematocrit, where red blood cells are separated from blood plasma and the other cellular components. Industrial centrifuges are expensive and generally employed in academic or clinical contexts. A bicycle centrifuge, on the contrary, may be designed and implemented in more generalized settings. Moreover, a bicycle centrifuge affords the opportunity to relate principles in physics to concepts specific to other scientific disciplines, such as biology and kinesiology

Interaction of urea with frequency and amount of distillers grains supplementation for growing steers on a high forage diet

Two studies were conducted to determine interactions of urea inclusion to a dried distillers grains plus solubles (DDGS; 29.4% crude protein, 5.48% ether extract) supplement fed at two amounts and two frequencies to steers on a high forage diet. In Exp. 1, 120 (247 kg; SD = 20) steers were fed individually for 84 d. Steers received ad libitum grass hay (6.8% crude protein) and one of eight treatments. Treatment design was a 2 × 2 × 2 factorial. Supplement was fed daily or three times per week, amount of supplement fed was 6.36 kg dry matter (DM)/week [0.37% body weight (BW); LO] or 12.73 kg DM/week (0.74% BW; HI) and contained either no urea or 1.3% urea on a DM basis. Steer BW was measured at the start and end of the trial and hay DM intake (DMI) was measured weekly. In Exp. 2, ruminally cannulated steers (310 kg; SD = 25) were used in a row-column design with eight steers and six 14-d periods. Treatments assigned were the same as Exp. 1, except that supplement was fed at 0.4% of BW (LO) or 0.8% of BW (HI) and supplement was fed either daily (DY) or every other day (ALT). Hay DMI, rumen ammonia-N, rumen pH, in situ neutral detergent fiber (NDF) disappearance, and rumination were measured. In Exp. 1, average daily gain (ADG) was affected by amount of supplement with steers on HI gaining 0.30 kg/d more (P \u3c 0.01) than LO. Hay DMI was reduced by increased amount of supplement (0.39 kg/d; P \u3c 0.01) and by decreased frequency of supplementation (0.54 kg/d; P \u3c 0.01). In Exp. 2, hay DMI was also reduced due to increased amount of supplement and decreased frequency of supplementation (P \u3c 0.01). Rumen pH was decreased on the day of supplement feeding for steers on ALT (P \u3c 0.01) and reduced for steers fed HI vs. LO. There was no difference in NDF digestibility between DY and ALT (P \u3e 0.05). For ALT steers, there was reduction (P \u3c 0.01) in in situ NDF disappearance for the HI compared to LO amount of supplementation on the day of supplementation. Infrequent supplementation of DDGS results in no difference in ADG but decreased hay DMI compared to daily supplementation. Urea had no effect on digestion or ADG, suggesting rumen degradable protein was not deficient when supplementing DDGS. There is little change in rumen fermentation parameters between frequency of supplement feeding, indicating that forage digestion is not impacted by supplementation frequency. Dried distillers grains can be supplemented infrequently without a reduction in animal performance

Case Report Malignant Catatonia Warrants Early Psychiatric-Critical Care Collaborative Management: Two Cases and Literature Review

Malignant catatonia (MC) is a life-threatening manifestation which can occur in the setting of an underlying neuropsychiatric syndrome or general medical illness and shares clinical and pathophysiological features and medical comorbidities with the Neuroleptic Malignant Syndrome (NMS). The subsequent diagnosis and definitive therapy of MC are typically delayed, which increases morbidity and mortality. We present two cases of MC and review recent literature of MC and NMS, illustrating factors which delay diagnosis and management. When clinical features suggest MC or NMS, we propose early critical care consultation and stabilization with collaborative psychiatric management

Cost‐effectiveness analysis of low‐dose direct oral anticoagulant (DOAC) for the prevention of cancer‐associated thrombosis in the United States

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154607/1/cncr32724.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154607/2/cncr32724_am.pd

Design and Implementation of an Underwater Sound Recording Device

To monitor the underwater sound and pressure waves generated by anthropogenic activities such as underwater blasting and pile driving, an autonomous system was designed to record underwater acoustic signals. The underwater sound recording device (USR) allows for connections of two hydrophones or other dynamic pressure sensors, filters high frequency noise out of the collected signals, has a gain that can be independently set for each sensor, and allows for 2 h of data collection. Two versions of the USR were created: a submersible model deployable to a maximum depth of 300 m, and a watertight but not fully submersible model. Tests were performed on the USR in the laboratory using a data acquisition system to send single-frequency sinusoidal voltages directly to each component. These tests verified that the device operates as designed and performs as well as larger commercially available data acquisition systems, which are not suited for field use. On average, the designed gain values differed from the actual measured gain values by about 0.35 dB. A prototype of the device was used in a case study to measure blast pressures while investigating the effect of underwater rock blasting on juvenile Chinook salmon and rainbow trout. In the case study, maximum positive pressure from the blast was found to be significantly correlated with frequency of injury for individual fish. The case study also demonstrated that the device withstood operation in harsh environments, making it a valuable tool for collecting field measurements

Inhibition of angiogenesis and suppression of colorectal cancer metastatic to the liver using the Sleeping Beauty Transposon System

<p>Abstract</p> <p>Background</p> <p>Metastatic colon cancer is one of the leading causes of cancer-related death worldwide, with disease progression and metastatic spread being closely associated with angiogenesis. We investigated whether an antiangiogenic gene transfer approach using the <it>Sleeping Beauty </it>(SB) transposon system could be used to inhibit growth of colorectal tumors metastatic to the liver.</p> <p>Results</p> <p>Liver CT26 tumor-bearing mice were hydrodynamically injected with different doses of a plasmid containing a transposon encoding an angiostatin-endostatin fusion gene (Statin AE) along with varying amounts of SB transposase-encoding plasmid. Animals that were injected with a low dose (10 μg) of Statin AE transposon plasmid showed a significant decrease in tumor formation only when co-injected with SB transposase-encoding plasmid, while for animals injected with a higher dose (25 μg) of Statin AE transposon, co-injection of SB transposase-encoding plasmid did not significantly affect tumor load. For animals injected with 10 μg Statin AE transposon plasmid, the number of tumor nodules was inversely proportional to the amount of co-injected SB plasmid. Suppression of metastases was further evident in histological analyses, in which untreated animals showed higher levels of tumor cell proliferation and tumor vascularization than animals treated with low dose transposon plasmid.</p> <p>Conclusion</p> <p>These results demonstrate that hepatic colorectal metastases can be reduced using antiangiogenic transposons, and provide evidence for the importance of the transposition process in mediating suppression of these tumors.</p

Integrating value of research into NCI Clinical Trials Cooperative Group research review and prioritization: A pilot study

BackgroundThe Institute of Medicine has called for approaches to help maximize the return on investments (ROI) in cancer clinical trials. Value of Research (VOR) is a health economics technique that estimates ROI and can inform research prioritization. Our objective was to evaluate the impact of using VOR analyses on the clinical trial proposal review process within the SWOG cancer clinical trials consortium.MethodsWe used a previously developed minimal modeling approach to calculate VOR estimates for 9 phase II/III SWOG proposals between February 2015 and December 2016. Estimates were presented to executive committee (EC) members (N = 12) who determine which studies are sent to the National Cancer Institute for funding consideration. EC members scored proposals from 1 (best) to 5 based on scientific merit and potential impact before and after receiving VOR estimates. EC members were surveyed to assess research priorities, proposal evaluation process satisfaction, and the VOR process.ResultsValue of Research estimates ranged from −$2.1B to$16.46B per proposal. Following review of VOR results, the EC changed their score for eight of nine proposals. Proposal rankings were different in pre‐ vs postscores (P value: 0.03). Respondents had mixed views of the ultimate utility of VOR for their decisions with most supporting (42%) or neutral (41%) to the idea of adding VOR to the evaluation process.ConclusionsThe findings from this pilot study indicate use of VOR analyses may be a useful adjunct to inform proposal reviews within NCI Cooperative Clinical Trials groups.The Instiztute of Medicine has called for approaches to help maximize the return on investments in cancer clinical trials. The findings from this pilot study indicate use of value of research analyses may be a useful adjunct to inform proposal reviews within NCI Cooperative Clinical Trials groups.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146484/1/cam41657.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146484/2/cam41657_am.pd