Biomedical subjects

Deborah A Marshall

Publications and source records attributed to Deborah A Marshall.

7 recordsLinked to original sources

PubMed2026

Complement Activation Linked to Type II Interferon Signaling in Still Disease.

OBJECTIVE: Still disease (SD) is an autoinflammatory syndrome characterized by innate immune dysregulation. Although complement can drive inflammation, its involvement in SD remains to be defined. Thus, we aimed to assess complement activation in SD. METHODS: Complement was assessed using transcriptomic, proteomic, and in vitro approaches. RNA sequencing of monocytes was performed in healthy donors (n = 15), those with nonsystemic juvenile idiopathic arthritis (JIA; n = 8), patients with SD at onset (n = 19) and remission (n = 18), and those with macrophage activation syndrome (n = 2). Whole-blood NanoString analysis of complement and interferon (IFN)-related gene expression was conducted in patients with SD (active n = 41, inactive n = 33) and JIA (n > 600). Complement products and inflammatory mediators were measured by Luminex and enzyme-linked immunosorbent assay. Functional complement activity was evaluated in SD (active n = 30, inactive n = 67) and JIA sera (n = 12). In vitro assays examined monocytic C1q induction and complement-mediated CD8+ T cell activation. RESULTS: Transcriptomic analysis of monocytes from patients with SD at onset revealed enrichment of the complement cascade compared with patients in remission (adjusted P = 3.7 × 10-36), ranking among the top 10 up-regulated pathways. Classical complement genes (C1QB/C1QC) were markedly up-regulated in onset SD compared with patients with remission SD and JIA. Patients with active SD showed increased C1q, C3a, C5a, and terminal complement complex protein levels, with enhanced functional classical complement activity. Whole-blood C1QB/C1QC expression correlated with IFN-related markers, including interleukin-18, CXCL9, and CXCL10. Recombinant IFN-γ induced monocytic C1q, whereas C1q enhanced IFN-γ production by CD8+ T cells, supporting a feed-forward loop. CONCLUSION: SD is characterized by complement activation with marked up-regulation of C1q, which is closely linked to IFN-γ/type II signaling.

Journal Article↗

PubMed2026

Effect of Time to Start of Biologic Therapy on Treatment Response in Childhood Arthritis: Results From the UCAN CAN-DU Cohort.

OBJECTIVE: To estimate the effect of time from symptom onset to start of biologic treatment on achieving inactive arthritis within six months in a cohort of patients with juvenile idiopathic arthritis (JIA). METHODS: The international UCAN CAN-DU study prospectively enrolled patients with JIA across Canada and the Netherlands. A nested cohort study was performed and biologic-naive patients with nonsystemic JIA were included at the start of biologic therapy. The primary outcome was inactive arthritis at six months. Demographics, disease-related parameters, and treatment response were compared using (non)parametric tests among early (time symptom onset to biologic start: 0-6 months), intermediate (7-12 months), and late (13-24 months) treatment groups. A logistic regression model analyzed the effect of time to biologic start on the response at six months, adjusting for active joint count and physician global assessment. A graphical representation of the model was created. RESULTS: One hundred and thirty children with JIA were included (early: n = 35; intermediate: n = 46; late: n = 49), 66% were female, and the median age at symptom onset was 11.0 years. The proportion of patients that reach inactive arthritis in the early starters (83%) was significantly higher than in late starters (57%). For each month of delay to the start of biologic treatment, the adjusted odds of having active arthritis after six months of therapy was 1.09 (interquartile range: 1.02-1.17, P = 0.009). CONCLUSION: Early start of biologic therapies in patients with JIA was associated with a higher proportion of patients reaching inactive arthritis within six months, suggesting a window of opportunity to control disease activity.

Humans↗

PubMed2006

Using and interpreting cost-effectiveness acceptability curves: an example using data from a trial of management strategies for atrial fibrillation.

BACKGROUND: The cost-effectiveness acceptability curve (CEAC) is a method for summarizing the uncertainty in estimates of cost-effectiveness. The CEAC, derived from the joint distribution of costs and effects, illustrates the (Bayesian) probability that the data are consistent with a true cost-effectiveness ratio falling below a specified ceiling ratio. The objective of the paper is to illustrate how to construct and interpret a CEAC. METHODS: A retrospective cost-effectiveness analysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) randomized controlled trial with 4060 patients followed for 3.5 years. The target population was patients with atrial fibrillation who were 65 years of age or had other risk factors for stroke or death similar to those enrolled in AFFIRM. The intervention involved the management of patients with atrial fibrillation with antiarrhythmic drugs (rhythm-control) compared with drugs that control heart rate (rate-control). Measurements of mean survival, mean costs and incremental cost-effectiveness were made. The uncertainty surrounding the estimates of cost-effectiveness was illustrated through a cost-effectiveness acceptability curve. RESULTS: The base case point estimate for the difference in effects and costs between rate and rhythm-control is 0.08 years (95% CI: -0.1 years to 0.24 years) and -5,077 US dollars (95% CI: -1,100 dollars to -11,006 dollars). The CEAC shows that the decision uncertainty surrounding the adoption of rate-control strategies is less than 1.7% regardless of the maximum acceptable ceiling ratio. Thus, there is very little uncertainty surrounding the decision to adopt rate-control compared to rhythm-control for patients with atrial fibrillation from a resource point of view. CONCLUSION: The CEAC is straightforward to calculate, construct and interpret. The CEAC is useful to a decision maker faced with the choice of whether or not to adopt a technology because it provides a measure of the decision uncertainty surrounding the choice.

Aged↗

PubMed2006

Economic evaluation of controlled-release oxycodone vs oxycodone-acetaminophen for osteoarthritis pain of the hip or knee.

OBJECTIVE: To examine, in routine practice, the effectiveness and cost-effectiveness of oxycodone (OxyContin) compared with standard therapy for osteoarthritis pain. STUDY DESIGN: Open-label active-controlled randomized naturalistic 4-month study of oxycodone vs a combination of oxycodone-acetaminophen (Percocet). METHODS: Outcomes and health resource utilization data were collected by telephone interview. Effectiveness was measured among 485 patients as the proportion having at least 20% improvement from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index pain score. Quality-adjusted life-years (QALYs) were calculated from the Health Utilities Index 3 score. Cost-effectiveness was measured as cost per patient improved and the QALYs gained, using generic oxycodone-acetaminophen in the base case for the healthcare and societal perspectives. Uncertainty was evaluated using multiple 1-way sensitivity analyses and cost-effectiveness acceptability curves. RESULTS: Improvement occurred in 62.2% of patients with oxycodone and in 45.9% of patients with oxycodone-acetaminophen (P < .001). After adjustment for baseline differences, 0.0105 QALYs were gained with oxycodone compared with oxycodone-acetaminophen (P = .17). The mean societal costs per patient during 4 months were 7379 US dollars and 7528 US dollars for oxycodone and oxycodone-acetaminophen, respectively (P = .33). Oxycodone was more effective and less costly than oxycodone-acetaminophen based on the societal perspective (including costs associated with time lost). Based on the healthcare perspective (excluding costs associated with time lost), the cost-effectiveness of oxycodone was 4883 US dollars per patient improved and 75,810 US dollars per QALY gained. The base-case results were robust. CONCLUSIONS: From the societal perspective, oxycodone was more effective and less costly than oxycodone-acetaminophen. From the healthcare perspective, oxycodone (compared with generic oxycodone-acetaminophen) fell within the acceptable range of cost-effectiveness between 50,000 US dollars and 100,000 US dollars per QALY gained.

Acetaminophen↗

PubMed2004

Cost-effectiveness of rhythm versus rate control in atrial fibrillation.

BACKGROUND: Atrial fibrillation is the most common type of sustained cardiac arrhythmia, but recent trials have identified no clear advantage of rhythm control over rate control. Consequently, economic factors often play a role in guiding treatment selection. OBJECTIVE: To estimate the cost-effectiveness of rhythm-control versus rate-control strategies for atrial fibrillation in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM). DESIGN: Retrospective economic evaluation. Nonparametric bootstrapping was used to estimate the distribution of incremental costs and effects on the cost-effectiveness plane. DATA SOURCES: Data on survival and use of health care resources were obtained for all 4060 AFFIRM participants. Unit costs were estimated from various U.S. databases. TARGET POPULATION: Patients with atrial fibrillation who were 65 years of age or who had other risk factors for stroke or death, similar to those enrolled in AFFIRM. TIME HORIZON: Mean follow-up of 3.5 years. PERSPECTIVE: Third-party payer. INTERVENTIONS: Management of patients with atrial fibrillation with antiarrhythmic drugs (rhythm control) compared with drugs that control heart rate (rate control). OUTCOME MEASURES: Mean survival, resource use, costs, and cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: A mean survival gain of 0.08 year (P = 0.10) was observed for rate control. Patients in the rate-control group used fewer resources (hospital days, pacemaker procedures, cardioversions, and short-stay and emergency department visits). Rate control costs 5077 dollars less per person than rhythm control. RESULTS OF SENSITIVITY ANALYSIS: Cost savings ranged from 2189 dollars o 5481 dollars per person. Rhythm control was more costly and less effective than rate control in 95% of the bootstrap replicates over a wide range of cost assumptions. LIMITATIONS: Resource use was limited to key items collected in AFFIRM, and the results are generalizable only to similar patient populations with atrial fibrillation. CONCLUSION: Rate control is a cost-effective approach to the management of atrial fibrillation compared with maintenance of sinus rhythm in patients with atrial fibrillation similar to those enrolled in AFFIRM.

Anti-Arrhythmia Agents↗

PubMed2004

Resistance to antibiotics: administrative response to the challenge.

The authors discuss antibiotic resistance within a conceptual framework that illustrates the dynamic relationships among antibiotic, patient, and population factors. The complexity of these interactions makes it unlikely that any single intervention or approach will adequately address the problem of increasing rates of antibiotic resistance. A case study focused on Streptococcus pneumoniae in the context of community-acquired pneumonia provides a detailed examination of the manner in which antibiotic use, expenditures, and microbial resistance are affected by an administrative reimbursement restriction implemented by a single government payer.

Drug Costs↗

PubMed2003

Review of economic evaluations of radiofrequency catheter ablation for cardiac arrhythmias.

A systematic review of current studies on the cost effectiveness of catheter ablation for treatment of tachycardia in adults was undertaken. The results are summarized based on a predefined framework of principles for economic evaluation. Of 192 abstracts identified, only three cost effectiveness studies were identified. Each focused on a different and specific patient group with selected target disorders, and used decision analysis modelling to estimate cost effectiveness. Radiofrequency catheter ablation is likely to be economically attractive compared with drug therapy in adult patients with frequently symptomatic paroxysmal supraventricular tachycardia (radiofrequency catheter ablation dominates drug therapy options) or in ventricular tachycardia patients with pre-existing ischemic coronary disease (cost effectiveness ratio of about US $21,000 per quality adjusted life year), but not in the treatment of asymptomatic Wolff-Parkinson-White syndrome patients. However, these studies evaluated different types of tachycardias in differing patient populations and all are based on United States data, so decision-makers must be cautious when applying these results to a general population with tachycardia in the Canadian context.

Adult↗