Cost-Utility Analysis of Rituximab vs Mycophenolate Mofetil for the Treatment of Pemphigus Vulgaris.

Importance: There is an increasing body of literature that supports the use of rituximab as a first-line steroid-sparing agent in pemphigus vulgaris. However, the cost of rituximab is substantial compared with conventional agents, and there are limited health economic data to justify its use. Objective: To evaluate the cost-effectiveness of rituximab biosimilars relative to mycophenolate mofetil as a first-line steroid-sparing agent for moderate to severe pemphigus vulgaris. Design, Setting, and Participants: A cost-utility analysis over a 24-month time horizon was conducted from the perspective of the Australian health care sector using a modeled cohort of treatment-naive adult patients with moderate to severe pemphigus vulgaris. A Markov cohort model was constructed to simulate disease progression following first-line treatment with rituximab biosimilars or mycophenolate mofetil. The simulated cohort transitioned between controlled disease, uncontrolled disease, and death. Efficacy and utility data were obtained from available published literature. Cost data were primarily obtained from published government data. One-way and probabilistic sensitivity analyses were performed to assess uncertainty. Primary outcomes were the changes in cost and quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) over the 24 months. Interventions: Rituximab biosimilars and mycophenolate mofetil. Results: The simulated cohort of treatment-naive patients had a mean age of 50.8 years, a female-to-male ratio of 1.24, and moderate to severe disease as classified by the Harman criteria. First-line rituximab biosimilars were associated with a cost reduction of AU$639 and an improvement of 0.07 QALYs compared with mycophenolate mofetil, resulting in an ICER of -AU$8818/QALY. Rituximab biosimilars were therefore more effective and less costly compared with mycophenolate mofetil. Sensitivity analyses demonstrated that rituximab biosimilars remained cost-effective across a range of values for cost, utility, and transition probability input parameters and willingness-to-pay thresholds. Conclusions and Relevance: In this cost-utility analysis, rituximab biosimilars were cost-effective compared with mycophenolate mofetil for moderate to severe pemphigus vulgaris. Further investigation into its cost-effectiveness over a longer time horizon is necessary, but the favorable results of this study suggest that the high acquisition costs of rituximab biosimilars may be offset by its effectiveness and provide economic evidence in support of its listing on the Pharmaceutical Benefits Scheme for pemphigus vulgaris.

Responsiveness and convergent validity of QLU-C10D and EQ-5D-3L in assessing short-term quality of life following esophagectomy.

AIM: This study assessed the responsiveness and convergent validity of two preference-based measures; the newly developed cancer-specific EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D) relative to the generic three-level version of the EuroQol 5 dimensions (EQ-5D-3L) in evaluating short-term health related quality of life (HRQoL) outcomes after esophagectomy. METHODS: Participants were enrolled in a multicentre randomised controlled trial to determine the impact of preoperative and postoperative immunonutrition versus standard nutrition in patients with esophageal cancer. HRQoL was assessed seven days before and 42 days after esophagectomy. Standardized Response Mean and Effect Size were calculated to assess responsiveness. Ceiling effects for each dimension were calculated as the proportion of the best level responses for that dimension at follow-up/post-operatively. Convergent validity was assessed using Spearman's correlation and the level of agreement was explored using Bland-Altman plots. RESULTS: Data from 164 respondents (mean age: 63 years, 81% male) were analysed. HRQoL significantly reduced on both measures with large effect sizes (> 0.80), and a greater mean difference (0.29 compared to 0.16) on QLU-C10D. Both measures had ceiling effects (> 15%) on all dimensions at baseline. Following esophagectomy, ceiling effects were observed with self-care (86%), mobility (67%), anxiety/depression (55%) and pain/discomfort (19%) dimensions on EQ-5D-3L. For QLU-C10D ceiling effects were observed with emotional function (53%), physical function (16%), nausea (35%), sleep (31%), bowel problems (21%) and pain (20%). A strong correlation (r = 0.71) was observed between EQ-5D-3L anxiety and QLU-C10D emotional function dimensions. Good agreement (3.7% observations outside the limits of agreement) was observed between the utility scores. CONCLUSION: The QLU-C10D is comparable to the more widely applied generic EQ-5D-3L, however, QLU-C10D was more sensitive to short-term utility changes following esophagectomy. Cognisant of requirements by policy makers to apply generic utility measures in cost effectiveness studies, the disease-specific QLU-C10D should be used alongside the generic measures like EQ-5D-3L. TRIAL REGISTRATION: The trial was registered with the Australian New Zealand Clinical Trial Registry (ACTRN12611000178943) on the 15th of February 2011.

Outsourcing robotic-assisted operations to private hospitals: cost analysis of a retrospective cohort.

BACKGROUND: The Lyell McEwin Hospital entered into a public-private collaborative agreement in 2019 in order to access Da Vinci® Xi Surgical Systems (Intuitive Surgical, Sunnyvale, CA, USA) in private hospitals. This study aimed to examine the costs associated with usage of robot surgical systems under the agreement, and the potential for acquisition in the public hospital. METHODS: Retrospective data on robotic-assisted and equivalent operations performed between 1 May 2019 and 30 April 2020 were collected and formed subsequent model inputs. Cost data were from hospital records and the local Da Vinci® Xi distributor. Clinical workflow of operations was simulated with a decision-analytic model, with output being costs incurred. The model's base case scenario assumed 5% of cases were robotically assisted. RESULTS: A total of 35 robotic-assisted, 101 laparoscopic and 34 open operations were performed. Patients were predominantly male and overweight with multiple comorbidities. Length of stay and duration of operation were associated with increased costs (p < 0.001, r2 0.72). In the base case scenario, there was a cost of AU$26 424 per patient, with an open conversion rate of 11%. Increasing robotic-assisted case percentage resulted in reduced cost, open conversion rates and length of stay. Extrapolation of cost model data indicated if 50% were robotic-assisted cases, then the initial capital investment (assumed at AU$4 000 000) could be recovered in 10 years. CONCLUSION: Our model highlights potential advantages of performing greater numbers of robotic-assisted operations in a collaborative environment. Cost-effective analysis with prospective data could evaluate if these results are translatable and potentially support acquisition of robotic systems in the public sector.

Improving cost-effectiveness of endoscopic surveillance for Barrett's esophagus by reducing low-value care: a review of economic evaluations.

BACKGROUND: Individuals with Barrett's esophagus are believed to be at 30-120× risk of developing esophageal adenocarcinoma (EAC). Early detection and endoscopic treatment of dysplasia/early cancer confers a significant advantage to patients under surveillance; however, most do not progress past the non-dysplastic state of Barrett's esophagus (NDBE), which is potentially an inefficient distribution of health care resources. OBJECTIVES: This article aimed to review the outcomes of cost-effectiveness studies reducing low-value care in the context of endoscopic surveillance for non-dysplastic Barrett's esophagus (NDBE). METHODS: A systematic search was conducted by two reviewers in accordance with PRISMA guidelines. INCLUSION CRITERIA: cost-utility analyses of endoscopic surveillance of NDBE patients with at least one treatment strategy focused on reduction of surveillance. A narrative synthesis of economic evaluations was undertaken, along with an in-depth analysis of input parameters contributing to stated Incremental cost-effectiveness ratios (ICER). Study appraisal was performed using the consolidated health economic evaluation reporting standards (CHEERS) tool. RESULTS: 10 Studies met inclusion criteria. There was significant variation in cost-model structures, input parameters, ICER values, and willingness-to-pay thresholds between studies. All studies except one concluded guideline-specified endoscopic surveillance for NDBE patients was not cost-effective. Studies that explored a modified surveillance by deselection of low-risk NDBE patients found it to be a cost-effective strategy. CONCLUSION: Guideline specified endoscopic surveillance for NDBE was not found to be cost-effective in the studies examined. A modified endoscopic surveillance strategy removing individuals with the lowest risk for progression from NDBE to adenocarcinoma is likely to be cost-effective but is dependent on risk profile of patients excluded from surveillance.

Cost-effectiveness in surgery: concepts of cost-utility analysis explained.

Economic evaluations are increasingly becoming part of the surgical evidence base. With health and research guidelines emphasizing both clinical and economic benefits, surgeons will need to consider the impact of economic evaluations in the future. It seems reasonable that surgical costs in the public healthcare sector should be justified by the benefits that clinical interventions offer. Thus, it is vital to understand the methodological differences, reported outcomes and limitations of economic evaluations pertinent to surgical practice as well. As terminology and concepts can be unfamiliar to surgeons, understanding results from these studies can seem difficult. This article aims to inform surgical readers of the processes involved in performing economic evaluations to determine and compare the cost-effectiveness of treatments. The various types of economic evaluations, their uses, design characteristics, model parameters, interpretation of outputs, uncertainty analyses and notable limitations are considered. Through a hypothetical clinical example that compares costs and effects of surgical versus medical treatment for cancer, key concepts in economic evaluations are considered.

Embryonic periventricular endothelial cells demonstrate a unique pro-neurodevelopment and anti-inflammatory gene signature.

Brain embryonic periventricular endothelial cells (PVEC) crosstalk with neural progenitor cells (NPC) promoting mutual proliferation, formation of tubular-like structures in the former and maintenance of stemness in the latter. To better characterize this interaction, we conducted a comparative transcriptome analysis of mouse PVEC vs. adult brain endothelial cells (ABEC) in mono-culture or NPC co-culture. We identified > 6000 differentially expressed genes (DEG), regardless of culture condition. PVEC exhibited a 30-fold greater response to NPC than ABEC (411 vs. 13 DEG). Gene Ontology (GO) analysis of DEG that were higher or lower in PVEC vs. ABEC identified "Nervous system development" and "Response to Stress" as the top significantly different biological process, respectively. Enrichment in canonical pathways included HIF1A, FGF/stemness, WNT signaling, interferon signaling and complement. Solute carriers (SLC) and ABC transporters represented an important subset of DEG, underscoring PVEC's implication in blood-brain barrier formation and maintenance of nutrient-rich/non-toxic environment. Our work characterizes the gene signature of PVEC and their important partnership with NPC, underpinning their unique role in maintaining a healthy neurovascular niche, and in supporting brain development. This information may pave the way for additional studies to explore their therapeutic potential in neuro-degenerative diseases, such as Alzheimer's and Parkinson's disease.

Evolving role of biomaterials in diagnostic and therapeutic radiation oncology.

Radiation therapy to treat cancer has evolved significantly since the discovery of x-rays. Yet, radiation therapy still has room for improvement in reducing side effects and improving control of cancer. Safer and more effective delivery of radiation has led us to novel techniques and use of biomaterials. Biomaterials in combination with radiation and chemotherapy have started to appear in pre-clinical explorations and clinical applications, with many more on the horizon. Biomaterials have revolutionized the field of diagnostic imaging, and now are being cultivated into the field of theranostics, combination therapy, and tissue protection. This review summarizes recent development of biomaterials in radiation therapy in several application areas.

Halitosis and Pain Post Electrocautery Adenoidectomy.

Background and Objectives: Electrocautery adenoidectomy (ECA) is a common procedure performed in paediatric otolaryngology. ECA has been preferred over curettage adenoidectomy due to its lower intraoperative bleeding rates, decreased procedure time, and higher subjective success. However, post-ECA symptoms of pain and halitosis have never been studied. The objective of our study was to identify the pattern of post-ECA halitosis and pain in the paediatric population. Materials and Methods: This is a single centre, prospective observational study that uses visual analogue scales (VAS) by parent proxy to assess post-ECA pain and halitosis in paediatric patients (age < 18) in South Australia. A total of 19 patients were enrolled in the study and followed for seven days. Results: Postoperative pain and halitosis reaches a peak 3 days post-ECA (median = 2 for pain; median = 6 for halitosis) but resolves 7 days post-ECA (median = 0 for both). Conclusions: Our study demonstrates that halitosis and pain occur over a seven-day period in patients undergoing ECA and will resolve post-operatively with simple analgesia and without antibiotics.

Challenges in Translating from Bench to Bed-Side: Pro-Angiogenic Peptides for Ischemia Treatment.

We describe progress and obstacles in the development of novel peptide-hydrogel therapeutics for unmet medical needs in ischemia treatment, focusing on the development and translation of therapies specifically in peripheral artery disease (PAD). Ischemia is a potentially life-threatening complication in PAD, which affects a significant percentage of the elderly population. While studies on inducing angiogenesis to treat PAD were started two decades ago, early results from animal models as well as clinical trials have not yet been translated into clinical practice. We examine some of the challenges encountered during such translation. We further note the need for sustained angiogenic effect involving whole growth factor, gene therapy and synthetic growth factor strategies. Finally, we discuss the need for tissue depots for de novo formation of microvasculature. These scaffolds can act as templates for neovasculature development to improve circulation and healing at the preferred anatomical location.

ABO blood group related venous thrombosis risk in patients with peripherally inserted central catheters.

OBJECTIVE: To investigate the association between ABO blood group and upper limb venous thrombosis (VT) risk in patients with peripherally inserted central catheters (PICC). METHODS: Single centre retrospective cohort study. A cohort of patients who underwent PICC insertion from September 2010 to August 2014 were followed up for symptomatic VT presentations diagnosed by ultrasound. Blood group status was identified from hospital information systems. RESULTS: 2270 participants had 3020 PICCs inserted. There were 124 cases of symptomatic VT, an incident rate of 4% [95% confidence interval, CI (3-5%)]. Univariate analysis adjusting for the clustered sample showed that having chemotherapy, two or more previous PICCs, a larger catheter size, a diagnosis of cancer and having a blood group B were all associated with an increased risk of a VT. In the multivariate analysis, PICC diameter, cancer diagnosis and blood group B were all independently associated with increased risk of VT. CONCLUSION: Patients undergoing PICC insertion with a blood group B appear to have a higher risk of VT, independent of risks attached to the PICC procedure and cancer diagnosis. Without any existing guidelines for PICC-related VT, this investigation creates a platform for further research to be conducted in order to establish guidelines. Advances in knowledge: Previous studies investigating VT risk associated with blood group status related to large heterogeneous populations. In this article, we look at patients specifically with PICC, which reduces the heterogeneity in the cohort. In addition, due to the substantial number of patients enrolled, we had a chance to perform multivariate analyses with statistical significance.

Bidirectional crosstalk between periventricular endothelial cells and neural progenitor cells promotes the formation of a neurovascular unit.

Interactions between neural progenitor cells (NPC) and endothelial cells (EC) from adult vascular beds have been well explored previously. However, the factors and signaling mechanisms that regulate neurogenesis and angiogenesis are most prevalent during embryonic development. This study aimed to determine whether embryonic brain endothelial cells from the periventricular region (PVEC) present an advantage over adult brain EC in supporting NPC growth and differentiation. PVEC were isolated from E15 mouse brains, processed, and sorted with immunomagnetic beads using antibodies against CD31/PECAM. On immunofluorescence (IF) staining, nearly all cells were positive for EC markers CD31 and CD144/VE-Cadherin. In proliferation studies, NPC proliferation was highest in transwell co-culture with PVEC, approximately 2.3 fold increase compared to baseline versus 1.4 fold increase when co-cultured with adult brain endothelial cells (ABEC). These results correlated with the PVEC mediated delay in NPC differentiation, evidenced by high expression of progenitor marker Nestin evaluated by IF staining. Upon further characterization of PVEC in an angiogenesis assay measuring cord length, PVEC exhibited a high capacity to form cords in basal conditions compared to ABEC. This was enhanced in the presence of NPC, with both cell types displaying a preferential structural alignment resembling neurovascular networks. PVEC also expressed high Vegfa levels at baseline in comparison to NPC and ABEC. Vegfa levels increased when co-cultured with NPC. We demonstrate that PVEC and NPC co-cultures act synergistically to promote the formation of a neurovascular unit through dynamic and reciprocal communication. Our results suggest that PVEC/NPC could provide promising neuro-regenerative therapies for patients suffering brain injuries.

Analysis of venous drainage in three patients with extradural spinal arteriovenous fistulae at the craniovertebral junction with potentially benign implication.

BACKGROUND: Extradural arteriovenous fistulae (AVFs) are vascular malformations that result from a direct connection between an extradural artery and vein, resulting in a high flow fistula that drains into the epidural venous system. Extradural AVFs may cause myelopathy when distended epidural veins compress the cord or when venous hypertension causes venous stasis within the spinal cord, and are uncommon causes of subarachnoid hemorrhage (SAH), although the presence of intracranial drainage is a risk factor for SAH. There are numerous reports of SAH and AVF with rostral intracranial venous drainage, implying an intradural drainage pathway. To our knowledge, a cervical spinal AVF at the craniovertebral junction (occurring between the occiput and C2) with exclusively extradural drainage and without a significant epidural component has not been described previously. METHODS: A retrospective review was performed identifying three patients treated at our hospital with cervical spinal AVF and extradural venous drainage. RESULTS: We present three cases of cervical spinal AVF with exclusive extradural venous drainage without accompanying intradural drainage--cranial or spinal. All three patients with exclusively extradural drainage have done well after 24 months of follow-up. The anatomical, clinical, and radiologic features are presented. CONCLUSIONS: Patients with cervical AVF and exclusively extradural drainage pathways form a separate entity, representing a subset with a less ominous natural history.