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Background: Invasive mold infections (IMI) directly impact life expectancy, especially with delayed therapy. Among IMI, aspergillosis (IA) is more common than mucormycosis (IM), resulting in IA-targeted empirical treatment with voriconazole for suspected invasive pulmonary aspergillosis (IPA), despite IM ineffectiveness. Recently, isavuconazole was approved in Canada for IA and IM. The primary objective was to assess the cost-effectiveness of isavuconazole compared to voriconazole for suspected IPA in Canada. A secondary objective was to assess the impact of varying time horizons to address the wide spectrum of life expectancies, according to patients underlying diseases., Research Design and Methods: A 5-year decision-tree was developed from the Canadian Ministry of Health (MoH) and societal perspectives. Efficacy parameters were extracted from SECURE/VITAL trials. Costs included treatment acquisition, hospitalization, adverse events and productivity loss. 3- and 10-year time horizon alternative scenarios and extensive sensitivity analyses were also conducted., Results: From a MoH perspective, isavuconazole compared to voriconazole resulted in an incremental cost-utility ratio (ICUR) of $C30,160/QALY. 3- and10-year ICURs were also cost-effective, relative to a willingness-to-pay threshold of $C50,000/QALY., Conclusions: This study demonstrates that, in comparison to voriconazole, isavuconazole is a cost-effective strategy for the treatment of patients with suspected IPA, regardless of their life expectancy.

Background: Vismodegib is a novel Hedgehog pathway inhibitor that has revolutionized the treatment of patients with advanced basal cell carcinoma (BCC) who are poor candidates for surgery or radiation. Few studies have explored the use of vismodegib to facilitate further surgery or radiotherapy, and the optimal treatment duration to balance outcomes with adverse effects., Objectives: To characterize the disease response, progression, and recurrence outcomes of BCC patients, and to report the impact of subsequent therapies., Methods: We performed a retrospective study of 46 adult patients with advanced basal cell carcinoma (aBCC), including both locally advanced (laBCC) and metastatic (mBCC) disease, treated with vismodegib at a single center from 2012 to 2019., Results: Thirty-six had laBCC, and 10 had mBCC. Treatment was given over a mean of 21.9 months. Twenty-three (50%) had a complete response (CR), and 19 (41.3%) achieved partial response (PR). Median time to maximal response was 5.3 months. Eleven (23.9%) had resected disease at median 17.2 months, and 11 patients (23.9%) received radiotherapy. Thirty-two (69.6%) experienced progressive disease after achievement of CR or PR. Among 17 CR patients, who stopped treatment, 14 (82.3%) experienced subsequent relapse; 6 (85%) attained a repeat response. Twenty (43.5%) discontinued treatment at least once due to adverse effects., Conclusions: With a response rate of 91%, London Regional Cancer Center's (LRCP)'s experience with vismodegib supports its effectiveness in treatment of aBCC. Moreover, a significant number of patients treated with vismodegib became amenable to surgery or radiotherapy. Toxicity remained an important factor that limited treatment duration.

Objective/background: Lemborexant is a dual orexin receptor antagonist approved in the United States, Japan, and Canada for the treatment of insomnia in adults. We report effectiveness and safety outcomes in subjects with insomnia who received up to twelve months of continuous lemborexant treatment in Study E2006-G000-303 (Study 303; SUNRISE-2)., Patients/methods: Study 303 was a twelve-month, global, multicenter, randomized, double-blind, parallel-group, Phase 3 study divided into two treatment periods. In Treatment Period 1 (first six months), subjects (n = 949, Full Analysis Set) were randomized to daily placebo, lemborexant 5 mg (LEM5) or lemborexant 10 mg (LEM10). In Treatment Period 2 (second six months), placebo subjects were rerandomized to LEM5 or LEM10, and subjects randomized to lemborexant continued their assigned treatment (LEM5, n = 251; LEM10, n = 226). Sleep onset and sleep maintenance endpoints were analyzed from daily electronic sleep diary data. Treatment-emergent adverse events (TEAEs) were monitored., Results: For all sleep parameters, the significant benefits observed with LEM5 and LEM10 versus placebo over six months were maintained at twelve months in subjects who received twelve continuous months of treatment. There was no evidence of rebound insomnia or withdrawal in either lemborexant group following treatment discontinuation. Over twelve months of lemborexant treatment, most TEAEs were mild/moderate; the most common TEAEs were nasopharyngitis, somnolence and headache., Conclusions: LEM5 and LEM10 had significant benefit on sleep onset and sleep maintenance compared with placebo, and importantly, lemborexant effectiveness persisted at twelve months, suggesting that lemborexant may provide long-term benefits for subjects with insomnia., Clinical Trial Registration: ClinicalTrials.gov, NCT02952820; ClinicalTrialsRegister.eu, EudraCT Number 2015-001463-39., (Copyright © 2021 Eisai Inc. Published by Elsevier B.V. All rights reserved.)

Background: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2- ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study (NCT03159195) collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada., Methods: This retrospective chart review included women with HR+/HER2- ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan-Meier analysis., Results: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%., Conclusions: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.

Objective: The management of advanced basal cell carcinoma (BCC) in the periocular region remains a clinical challenge. Vismodegib (Erivedge TM ) has been approved in 2013 by Health Canada for adult patients with "histologically confirmed metastatic BCC or locally advanced BCC inappropriate for surgery or radiation." An expert consensus was sought to create a standardised approach in the use of this novel treatment., Methods: Fourteen practicing oculoplastic surgeons across Canada were involved in formulating and reviewing guidelines until consensus was reached. A consultancy meeting was followed by further ratification of guidelines over email. Two voting surveys were performed of the group to objectively assess agreement over each statement within the guidelines. Ratification continued until at least two-thirds of the group agreed on every guideline statement., Results: The guidelines summarize 21 statements in a major and minor criteria format. A multidisciplinary team review is suggested for each patient with the involvement of recommended specialists. The internal survey revealed 100% agreement over 9 statements, 91.7% agreement over 8 statements, 83.3% agreement over 4 statements, and 2 statements had 66.7% and 58.7% agreement each. All statements with less than 91.7% agreement were surveyed again, and they were kept, modified, or removed on the basis of a consensus of over 66.7%., Conclusions: These guidelines serve to act as a framework for physicians considering vismodegib for the medical management of patients with advanced or metastatic periocular BCC. Future applications, including neoadjuvant uses of the drug, may become apparent through further research., (Copyright © 2019 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

The use of sulfonylurea herbicides (SU) has increased greater than 100 times over the past 30 years in both Europe and North America. Applied at low rates, their presence, persistence and potential impacts on aquatic ecosystems remain poorly studied. During late-spring to early fall in 2009-2011, concentrations of 9 SU were assessed in two agricultural streams and their receiving wetland, an enlargement of the St. Lawrence River (Canada). Six SU in concentrations >LOQ (10 ng L(-1)) were detected in 10% or less of surface water samples. Rimsulfuron was detected each year, sulfosulfuron and nicosulfuron in two years and the others in one year only, suggesting that application of specific herbicides varied locally between years. Detection frequency and concentrations of SU were not significantly associated with total precipitation which occurred 1 to 5d before sampling. Concentrations and fate of SU differed among sites due to differences in stream dynamics and water quality characteristics. The persistence of SU in catchment basin streams reflected the dissipation effects associated with stream discharge. Maximum concentrations of some SU (223 and 148 ng L(-1)) were occasionally above the baseline level (100 ng L(-1)) for aquatic plant toxicity, implying potential toxic stress to flora in the streams. Substantially lower concentrations (max 55 ng L(-1)) of SU were noted at the downstream wetland site, likely as a result from dilution and mixing with St. Lawrence River water, and represent less toxicological risk to the wetland flora. Sporadic occurrence of SU at low concentrations in air and rain samples indicated that atmospheric deposition was not an important source of herbicides to the study area., (Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.)

This study represents the first national survey of optometrists in Canada. A mailed questionnaire was designed and implemented in order to discover how optometrists have reacted to the introduction of diagnostic pharmaceutical agent (DPA) legislation in Canada and to determine what variables are important predictors of DPA use. The data collected were also used to test the null hypothesis that DPA legislation does not affect the use of mydriatic/cycloplegic agents by optometrists. A stratified random sampling procedure was used to select 230 optometrists (roughly 10% of the practicing profession) for inclusion in the study. Over 90% of the subjects completed and returned the questionnaire. A statistically significant and important association was found between mydriatic/cycloplegic drug use and legislation (p less than 0.05 and odds ratio = 2.18). Legislation, type of practice, age, and optometry school attended were all found to be associated with DPA use.