Real-World Patient Experience of Pexidartinib for Tenosynovial Giant-Cell Tumor.

BACKGROUND: Pexidartinib (Turalio) is the only systemic therapy approved by the FDA for the treatment of adult patients with symptomatic tenosynovial giant-cell tumor (TGCT) associated with severe morbidity or functional limitations, and not amenable to improvement with surgery. This study assessed patient-reported treatment experiences and symptom improvement among patients receiving pexidartinib. METHODS: A cross-sectional, web-based survey collected data on demographics, disease history, pexidartinib dosing, and symptoms before and after pexidartinib use. RESULTS: Of 288 patients enrolled in the Turalio REMS program in May 2021, 83 completed the survey: mean age was 44.2 years, 62.7% were female, and most common tumor sites were in knee (61%) and ankle (12%). Mean initial dose was 622 mg/day: 29 patients reported reduction from initial dose and 8 had dose reduction after titrating up to a higher dose. At the time of survey completion, median time on pexidartinib was 6.0 months; 22 (26.5%) patients discontinued pexidartinib due to physician suggestion, abnormal laboratory results, side effect, or symptom improvement. Compared with before pexidartinib initiation, most patients reported improvement in overall TGCT symptom (78.3%) and physical function (77.2%) during pexidartinib treatment. Significant improvement was reported during pexidartinib treatment in worst stiffness numeric rating scale (NRS) (3.0 vs. 6.2, P < .05) and worst pain NRS (2.7 vs. 5.7, P < .05). CONCLUSION: Findings from this cross-sectional survey confirmed the benefit of pexidartinib in improving symptoms and functional outcomes among patients with symptomatic TGCTs from the patients' perspective. Future research is warranted to examine the long-term benefit and risk of pexidartinib.

Barriers to the universal adoption of bilateral internal mammary artery grafting.

The left internal mammary artery (LIMA) graft is considered the "gold standard" of coronary artery bypass grafting (CABG). This conduit provides increased survival, symptomatic relief, increased freedom from myocardial infarction, and increased freedom from re-intervention when compared to saphenous venous grafting. It has a remarkable long term patency rate with clinical and angiographic outcomes that are unmatched by other conduits. Given the fact that patients often require more than one graft during a coronary revascularization procedure, the prospect of bilateral internal mammary artery (BIMA) grafting has been very appealing to some surgeons. BIMA grafting has been extensively studied via multiple retrospective and prospective cohort studies and findings have indicated that BIMA grafting can have an increased survival benefit when compared to LIMA grafting alone. As a result, this technique has accrued increasing popularity over the course of the last decade. Yet, questions still remain on whether BIMA grafting is the optimal treatment modality for patients in terms of long-term prognosis. There is limited data at the present time from randomized controlled trials and only 4-12% of CABGs performed today utilize BIMA grafting. Concerns regarding perioperative complications, which patient subsets are at higher risks for complications from the technique, and the technical challenges involved in utilizing and teaching the technique have limited its widespread use.

A randomized clinical trial of selective laser trabeculoplasty versus argon laser trabeculoplasty in patients with pseudoexfoliation.

PURPOSE: To evaluate the efficacy of selective laser trabeculoplasty (SLT) versus argon laser trabeculoplasty (ALT) in lowering the intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension secondary to pseudoexfoliation. DESIGN: Multicentered randomized clinical trial. PARTICIPANTS: A total of 76 eyes from 60 patients with pseudoexfoliation and uncontrolled IOP were recruited from 5 Canadian academic institutions. Patients with prior laser trabeculoplasty, ocular surgery within 6 months, previous glaucoma surgery, an advanced visual field defect, current steroid use, and monocular patients were excluded. METHODS: Eyes were randomized to receive either 180-degree SLT or 180-degree ALT by a nonblocked randomization schedule stratified by center. MAIN OUTCOME MEASUREMENT: The primary outcome was the change in IOP at 6 months versus baseline and secondary outcomes included change in number of glaucoma medications after laser. Baseline variables included age, sex, angle grade, angle pigmentation, and number of glaucoma medications. RESULTS: Of the 76 eyes, 45 eyes received SLT and 31 eyes received ALT. The overall age was 72.9 years (65% females). The baseline IOPs in the SLT and ALT groups were 23.1 and 25.2 mm Hg, respectively (P=0.03). The IOP reduction 6 months after SLT was -6.8 mm Hg and post-ALT was -7.7 mm Hg (P>0.05). The SLT group had reduced glaucoma medications by 0.16 medications at 6 months and the ALT group had no decrease in medications over the same time period (P=0.59). There were no postlaser IOP spikes in either group. DISCUSSION: ALT and SLT are equivalent in lowering IOP at 6 months posttreatment in patients with PXF.

An investigation of the relationship between cataract surgery wait times and rates of surgery.

OBJECTIVE: The relationship between cataract surgery wait times and rates of surgery was investigated to determine whether wait times correlate with rates of surgery. DESIGN: Cross-sectional study. PARTICIPANTS: We collected 2 Ontario registries for cataract surgeries: (i) Cancer Care Ontario wait time registry; and (ii) The Ontario Health Insurance Plan billing records. METHODS: Both registries were used to determine whether wait times correlated with rates of surgery, and the data were then stratified by region of the province, priority (severity) of cases, age, and sex. RESULTS: The total number of surgeries performed between April 2, 2007, and March 31, 2008, was 65,520. The overall mean number of wait days was 69.8 days; the mean patient age was 72.5 years; and the surgery rate was 540.3 per 100,000 members of the population. For high-priority cases (priorities 1 and 2), there was a very weak inverse correlation (p = -0.27 and -0.21) between wait time and surgery rate, whereas the overall correlation between wait time and surgical rate was close to zero in both databases, regardless of the region, the patients' ages, and the patients' genders. CONCLUSIONS: This study demonstrates a very weak correlation between wait times for and rates of cataract surgery, and this should be a concern for policy makers. Further study is needed to see whether this null relationship persists over time and whether it exists for other monitored wait time procedures. Reasons for this null relationship will have to be determined and remedied as the use of wait times becomes a more widespread outcome in Canadian Healthcare.

Pharmacologic management of neovascular age-related macular degeneration: systematic review of economic evidence and primary economic evaluation.

OBJECTIVE: To examine the economic implications for the Canadian health system of pharmacologic treatment of neovascular age-related macular degeneration (AMD). DESIGN: Systematic review of economic literature and a primary economic evaluation. PARTICIPANTS: Economic literature search identified 392 potentially relevant articles, 12 of which were included for final review. METHODS: Studies were included if they met the following criteria: (i) provision of a summary measure of the trade-off between costs and consequences; (ii) participants of 40 years and older with neovascular AMD; (iii) interventions and comparators: comparison of photodynamic therapy using verteporfin (V-PDT), pegaptanib, bevacizumab, ranibizumab, anecortave acetate, intravitreal triamcinolone, placebo, or clinically relevant combinations; and (iv) outcome reported as an incremental measure of the implication of moving from the comparator to the intervention. The following databases were searched through the OVID interface: MEDLINE, EMBASE, BIOSIS Previews, CINAHL, PubMed, Health Economic Evaluations Database (HEED), and the Cochrane Library. For the economic evaluation, we took a decision analytic approach and modeled a cost-utility analysis, conducting it as a microsimulation of a Markov model. RESULTS: In general, V-PDT is more cost effective than conventional macular laser, and pegaptanib is likely more cost effective than V-PDT. The primary economic analysis revealed ranibizumab to be effective but at an unacceptably high cost per quality-adjusted life year (QALY)(>$50,000 per QALY). CONCLUSIONS: Although ranibizumab is effective for wet AMD, its cost is unacceptably high based on cost-utility theory.

Endoscopic goniotomy: early clinical experience in congenital glaucoma.

PURPOSE: To review the technique and early outcomes of endoscopic goniotomy (EG) in children with opaque corneas and primary congenital glaucoma (PCG) or developmental glaucoma with ocular or systemic anomalies (DG). METHODS: EG was performed for approximately 300 degrees of the angle through temporal and superonasal corneal incisions. We retrospectively reviewed consecutive cases from 2003 to 2007. Primary outcome was intraocular pressure (IOP) change from baseline to last postoperative visit. Success was defined as IOP < or=21 mm Hg with or without medication but no further surgical intervention. RESULTS: Fourteen eyes of 8 patients (4 PCG, 4 DG) were included. Mean age at surgery was 3.88+/-3.72 months. The reduction in IOP from baseline to the last follow-up visit was -16.7+/-16.7 mm Hg. Success was achieved in 6 of the 16 eyes (Total=43%, PCG=50%, DG=30%). Corneal diameter and axial length remained stable in all eyes. Two patients with DG needed additional surgery after 8 to 9 months. Complications included cataract and zonular dialysis both in 2 patients with aniridia. CONCLUSIONS: This pilot study indicates that EG shows reasonable potential for IOP control in congenital glaucoma. The safety and efficacy of EG needs to be further studied with a larger sample size and comparison to other angle surgery techniques.

Consequences of testing for celiac disease.

Population screening studies have identified that up to two thirds of celiac disease (CD) cases are asymptomatic. The aim of this study was to conduct a systematic review of the expected consequences of testing for CD in the following populations: (1) patients with symptoms suggestive of CD, (2) asymptomatic at-risk populations, and (3) general population. Standard systematic review methodology was used. A comprehensive literature search was conducted in MEDLINE (1996-2003), EMBASE (1974-2003), CAB (1972 forward), PsychINFO (1840-2003), AGRICOLA (1970-2003), and Sociological Abstracts (1963 forward); searches were conducted in December 2003. Pooled summary estimates were not calculated. The majority of the included studies were before-after studies, case control, or retrospective cohorts. The quality of evidence for the before-after studies is weaker. The overall strength of the evidence for this issue was fair to good. This area of research is relatively new, and further high-quality studies are required. The consequences of testing for celiac disease in symptomatic individuals appears to have a positive impact on patient-relevant outcomes. The data are less clear for those with silent CD or those with lower grade histologic lesions in small bowel biopsy. The literature suggests that compliance is less than ideal in these individuals, especially if diagnosed when adults. Long-term outcomes have not been extensively studied in those with silent CD.