The Clinical and Economic Implications of Different Treatment Pathways for Patients With Rapidly Recurrent Malignant Pleural Effusion.

BACKGROUND: Malignant pleural effusion (MPE) is a common cancer complication. Clinical and economic implications of different recurrent MPE treatment pathways have not been evaluated fully. RESEARCH QUESTION: What clinical outcomes, complications, health care resource use, and costs are associated with various rapidly recurrent MPE treatment pathways? STUDY DESIGN AND METHODS: This retrospective cohort study using Surveillance, Epidemiology and End Results Medicare data (2011-2015) included patients 66 to 90 years of age with rapidly recurrent MPE. Rapid recurrence was defined as receipt of a second pleural procedure within 14 days of the first thoracentesis, including nondefinitive repeated thoracentesis or a definitive treatment option including chest tube, indwelling pleural catheter (IPC), or thoracoscopy. RESULTS: Among 8,378 patients with MPE, 3,090 patients (36.9%) had rapidly recurrent MPE (mean ± SD age, 75.9 ± 6.6 years; 45.6% male; primary cancer, 62.9% lung and 37.1% other). Second pleural procedures were nondefinitive thoracentesis (62.3%), chest tube (17.1%), IPC (13.2%), or thoracoscopy (7.4%). A third pleural procedure was required more frequently if the second pleural procedure was nondefinitive thoracentesis vs chest tube placement, IPC placement, or thoracoscopy (70.3% vs 44.1% vs 17.9% vs 14.4%, respectively). The mean number of subsequent pleural procedures over the patient's lifetime varied significantly among the procedures (1.74, 0.82, 0.31, and 0.22 procedures for patients receiving thoracentesis, chest tube, IPC, and thoracoscopy, respectively; P < .05). Average total costs after the second pleural procedure to death adjusted for age at primary cancer diagnosis, race, year of second pleural procedure, Charlson comorbidity index, cancer stage at primary diagnosis, and time from primary cancer diagnosis to diagnostic thoracentesis were lower with IPC ($37,443; P < .0001) or chest tube placement ($40,627; P = .004) vs thoracentesis ($47,711). Patients receiving thoracoscopy ($45,386; P = .5) incurred similar costs as patients receiving thoracentesis. INTERPRETATION: Early definitive treatment was associated with fewer subsequent procedures and lower costs in patients with rapidly recurrent MPE.

Economic burden of needlestick injuries among healthcare workers in China.

Objective: To estimate the economic burden of needlestick injuries (NSIs) among healthcare workers (HCWs) in China.Design: A model was built to evaluate the economic burden of NSIs.Methods: The cost model was developed from a societal perspective, including both direct and indirect costs, with lifetime horizon. The direct costs were categorized into infection prevention and treatment of infections. The indirect cost included productivity loss of both HCWs and his/her family members due to the blood-borne infections. Sub-group analyses were conducted to estimate the cost per NSI when the source patient (SP) was confirmed with hepatitis B virus/hepatitis C virus/human immunodeficiency virus (HBV/HCV/HIV) infection. One-way and probabilistic sensitivity analyses were conducted for all parameters to examine the robustness of the result.Results: The model projected a total cost of ¥699 for each NSI (direct and indirect cost were ¥553 and ¥146, respectively). The cost per NSI when the SP was confirmed with HBV/HCV/HIV was ¥4,238, ¥18,404, and ¥6,152, respectively. The total economic burden of NSIs among HCWs in China was estimated to be ¥5.8 billion, and about half of the cost was associated with NSIs in nurses, at ¥2.8 billion.Limitations: This study did not incorporate the costs of litigation/psychological, and the prevalence of the infections was based on the general population, so the actual costs per NSI may be underestimated. More real-world studies of treatment cost about HBV/HCV are needed to further supporting this study.Conclusions: The economic burden of NSIs among HCWs in China is substantial. Comprehensive NSI prevention programs, including implementation of safety needles and devices, have high potential for healthcare institutions to achieve downstream cost savings and cost offsets.

The economic impact of poor sample quality in clinical chemistry laboratories: results from a global survey.

Background Despite advances in clinical chemistry testing, poor blood sample quality continues to impact laboratory operations and the quality of results. While previous studies have identified the preanalytical causes of lower sample quality, few studies have examined the economic impact of poor sample quality on the laboratory. Specifically, the costs associated with workarounds related to fibrin and gel contaminants remain largely unexplored. Methods A quantitative survey of clinical chemistry laboratory stakeholders across 10 international regions, including countries in North America, Europe and Oceania, was conducted to examine current blood sample testing practices, sample quality issues and practices to remediate poor sample quality. Survey data were used to estimate costs incurred by laboratories to mitigate sample quality issues. Results Responses from 164 participants were included in the analysis, which was focused on three specific issues: fibrin strands, fibrin masses and gel globules. Fibrin strands were the most commonly reported issue, with an overall incidence rate of ∼3%. Further, 65% of respondents indicated that these issues contribute to analyzer probe clogging, and the majority of laboratories had visual inspection and manual remediation practices in place to address fibrin- and gel-related quality problems (55% and 70%, respectively). Probe maintenance/replacement, visual inspection and manual remediation were estimated to carry significant costs for the laboratories surveyed. Annual cost associated with lower sample quality and remediation related to fibrin and/or gel globules for an average US laboratory was estimated to be $100,247. Conclusions Measures to improve blood sample quality present an important step towards improved laboratory operations.

Hydroxyethylene isosteres of selective neuronal nitric oxide synthase inhibitors.

Nitric oxide (NO) is an important second messenger molecule for blood pressure homeostasis, as a neurotransmitter, and in the immune defense system. Excessive NO can lead to neurodegeneration and connective tissue damage. Three different isozymes of the enzyme nitric oxide synthase regulate NO production in endothelial (eNOS), neuronal (nNOS), and macrophage (iNOS) cells. Whereas creating a lower level of NO in some cells could be beneficial, it also could be detrimental to the protective effects that NO has on other cells. Therefore, it is essential that therapeutic NOS inhibitors be made that are subtype selective. Previously, we reported a series of nitroarginine-containing dipeptide amides as potent and selective nNOS inhibitors. Here we synthesize peptidomimetic hydroxyethylene isosteres of these dipeptide amides for potential increased bioavailability. None of the compounds is as potent or selective as the dipeptide amides, but they exhibit good inhibition and selectivity. When the terminal amino group was converted to a hydroxyl group, potency and selectivity greatly diminished, supporting the importance of the terminal amino group for binding.

Exploring the binding conformations of bulkier dipeptide amide inhibitors in constitutive nitric oxide synthases.

A series of L-nitroarginine-based dipeptide inhibitors are highly selective for neuronal nitric oxide synthase (nNOS) over the endothelial isoform (eNOS). Crystal structures of these dipeptides bound to both isoforms revealed two different conformations, curled in nNOS and extended in eNOS, corresponding to higher and lower binding affinity to the two isoforms, respectively. In previous studies we found that the primary reason for selectivity is that Asp597 in nNOS, which is Asn368 in eNOS, provides greater electrostatic stabilization in the inhibitor complex. While this is the case for smaller dipeptide inhibitors, electrostatic stabilization may no longer be the sole determinant for isoform selectivity with bulkier dipeptide inhibitors. Another residue farther away from the active site, Met336 in nNOS (Val106 in eNOS), is in contact with bulkier dipeptide inhibitors. Double mutants were made to exchange the D597/M336 pair in nNOS with N368/V106 in eNOS. Here we report crystal structures and inhibition constants for bulkier dipeptide inhibitors bound to nNOS and eNOS that illustrate the important role played by residues near the entry to the active site in isoform selective inhibition.

Selective neuronal nitric oxide synthase inhibitors.

This review includes the non-patent literature up to October 2004 that deals with selective neuronal nitric oxide synthase inhibitors (highest potency is for the neuronal isozyme). Some non-selective inhibitors or selective inducible nitric oxide synthase inhibitors are mentioned if they are related to compounds that are discussed; structures of these compounds generally are not given. In vitro inhibition constants are given either as IC(50) values or as K(i)values. An IC(50) value, the inhibitor concentration that produces 50% inhibition in the presence of a constant concentration of substrate, is obtained by extrapolation of several rate data points to 50% inhibition. K(i) values are derived from several types of plots that relate the concentration of inhibitor with enzyme velocity in the presence of a variety of substrate concentrations [1]. The K(i) value can be estimated from the IC(50) value [2]. Although the two inhibition constants are related, they are not the same; generally, the reported K(i) values tend to be lower than the IC(50) values. If specifics are desired about how the data were collected, then the reader will have to look in the literature cited. No attempt was made to be exhaustive in citing all references related to specific inhibitors; rather, examples of literature references are given for each inhibitor described.