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Canada is known to have a complex pathway for new drug approval and reimbursement, resulting in delayed access for patients with serious and life-threatening diseases, such as cancer. Several recent publications from key stakeholders, including patients, physicians and policymakers, highlight patient helplessness, physician frustrations and policymakers entangled in a massive network of bureaucracy unable to make headway. Several quantitative and qualitative assessments using time from regulatory approvals to successful reimbursements confirm long review times and high rejection rates for oncology drugs, especially those receiving conditional approvals. A consensus forum of 18 Canadian oncology clinicians recently voiced frustration with the process and inability to deliver guideline-supported efficacious therapies to their patients. This manuscript compares data extracted from publicly available data sources from 2019 to June 2024 to previous publications. Methods: Public databases from Health Canada, the Canadian Agency for Drugs and Technologies in Health (CADTH), which is in the process of changing to Canada's Drug Agency, and the pan-Canadian Pharmaceutical Alliance (pCPA) were reviewed and the data collected were analyzed with descriptive statistics. Results: From the data, three trends emerge, (i) an increasing number of oncology drugs are receiving conditional approvals from Health Canada, (ii) the percentage of conditionally approved oncology drugs receiving positive reimbursement recommendations from CADTH is still low but appears to be improving, but delays in access are now contingent upon pCPA deciding whether to negotiate price and then the duration of any negotiation, and (iii) real-world evidence is no longer part of the decision-making for conditional approvals. A slight increase in the positive endorsement of RWE used to support CADTH recommendations was observed. Conclusions: The lack of timely access to oncology drugs hurts Canadian patients. While a small trend of improvement appears to be emerging, longer-term data collection is required to ensure sustained patient benefits. [ABSTRACT FROM AUTHOR]

Background: The dichotomy between the hypo- versus hyperkinetic nature of Parkinson’s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. In this study, we investigated differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections. Methods: Using microelectrode recording data collected from the GPi during deep brain stimulation surgery, we compared neuronal spiketrain features between people with PD and those with dystonia, as well as correlated neuronal features with respective clinical scores. Additionally, we characterized and compared readouts of short- and long-term synaptic plasticity using measures of inhibitory evoked field potentials. Results: GPi neurons were slower, burstier, and less regular in dystonia. In PD, symptom severity positively correlated with the power of low-beta frequency spiketrain oscillations. In dystonia, symptom severity negatively correlated with firing rate and positively correlated with neuronal variability and the power of theta frequency spiketrain oscillations. Dystonia was moreover associated with less long-term plasticity and slower synaptic depression. Conclusions: We substantiated claims of hyper- versus hypofunctional GPi output in PD versus dystonia, and provided cellular-level validation of the pathological nature of theta and low-beta oscillations in respective disorders. Such circuit changes may be underlain by disease-related differences in plasticity of striato-pallidal synapses. Funding: This project was made possible with the financial support of Health Canada through the Canada Brain Research Fund, an innovative partnership between the Government of Canada (through Health Canada) and Brain Canada, and of the Azrieli Foundation (LM), as well as a grant from the Banting Research Foundation in partnership with the Dystonia Medical Research Foundation (LM). [ABSTRACT FROM AUTHOR]

Drug repurposing has gained significant interest in recent years due to the high costs associated with de novo drug development; however, comprehensive pharmacological information is needed for the translation of pre‐existing drugs across clinical applications. In the present study, we explore the current pharmacological understanding of the orphan drug, hemin, and identify remaining knowledge gaps with regard to hemin repurposing for the treatment of cardiovascular disease. Originally approved by the United States Food and Drug Administration in 1983 for the treatment of porphyria, hemin has attracted significant interest for therapeutic repurposing across a variety of pathophysiological conditions. Yet, the clinical translation of hemin remains limited to porphyria. Understanding hemin's pharmacological profile in health and disease strengthens our ability to treat patients effectively, identify therapeutic opportunities or limitations, and predict and prevent adverse side effects. However, requirements for the pre‐clinical and clinical characterization of biologics approved under the U.S. FDA's Orphan Drug Act in 1983 (such as hemin) differed significantly from current standards, presenting fundamental gaps in our collective understanding of hemin pharmacology as well as knowledge barriers to clinical translation for future applications. Using information extracted from the primary and regulatory literature (including documents submitted to Health Canada in support of hemin's approval for the Canadian market in 2018), we present a comprehensive case study of current knowledge related to hemin's biopharmaceutical properties, pre‐clinical/clinical pharmacokinetics, pharmacodynamics, dosing, and safety, focusing specifically on the drug's effects on heme regulation and in the context of acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Titanium dioxide (TiO2), also known as E171, is commonly used as a white colorant in food, pharmaceuticals, cosmetics, and toothpaste. However, in May 2021, the European Food Safety Authority (EFSA) expert panel, in evaluating the safety of titanium dioxide (E171) as a food additive, concluded that a concern for genotoxicity could not be ruled out. This occurred several years after EFSA had previously considered titanium dioxide to be safe as a food additive. EFSA based this new interpretation on the results of genotoxicity tests of TiO2 nanomaterials. EFSA noted that available data are insufficient to define threshold doses/concentrations of TiO2 particles below which genotoxicity will not occur in tissues containing these particles. Here, it is argued that EFSA made a manifest error regarding the safety of titanium dioxide (E171) particles as a food additive for humans. First, the notion of particle size distribution of TiO2 particles is explained. Second, the changing opinions from the various EFSA evaluations in 2016, 2018, 2019 vs. 2021 are discussed. Third, the low toxicity of TiO2 particles is described in rats exposed by oral gavage and feeding studies in rats and mice. Fourth, the importance of low absorption rates from the gastrointestinal tract vs. circulation in rats and humans but not in mice is identified. Fifth, other international health scientists have weighed in on the EFSA (EFSA J, 2021, 19 (5), 6585) decision and generally disagreed with EFSA's opinion on the safety of E171 TiO2. A common theme voiced by the United Kingdom, Canada, Australia, and New Zealand agencies is that it is inappropriate to compare nanoparticle toxicity studies of dispersed/sonicated nanoparticles with the content of E171 TiO2 in foods because the test materials used in key studies considered by EFSA (EFSA J, 2021, 19 (5), 6585) are not representative of E171 TiO2 particles. Finally, a group of experts recently considered the genotoxicity of TiO2 and could not find support for a direct DNA damaging mechanism of TiO2 (nano and other forms). For these reasons, it is suggested that EFSA made a manifest error on the safety of E171 as a food additive. [ABSTRACT FROM AUTHOR]

DAVID died. He was 14 years old and the youngest of five boys. He missed the front step of the family's old and dilapidated house, and fell into the thick [...]

Globally, national regulatory authorities are both responsible and accountable for health and environmental decisions related to diverse products and risk decision contexts. These authorities provided regulatory oversight and expedited market authorizations of vaccines and other therapeutic products during the COVID-19 pandemic. Regulatory decisions regarding such products and situations depend upon well-established risk assessment and management steps. The underlying processes supporting such decisions were outlined in frameworks describing the complex interactions between factors including risk assessment and management steps as well as principles which help guide risk decision-making. In 2022, experts in risk science proposed a set of 10 guiding principles, further examining the intersection and utility of these principles using 10 diverse risk contexts, and inviting a broader discourse on the application of these principles in risk decision-making. To add to this information, Canadian regulatory practitioners responsible for evaluating health and environmental risks and establishing policies convened at a Health Canada workshop on Principles for Risk Decision-Making. This review reports the results derived from this interactive engagement and provides a first pragmatic analysis of the relevance, importance, and feasibility of such principles for health and environmental risk decision-making within the Canadian regulatory context. [ABSTRACT FROM AUTHOR]

The absence of a definitive cure for amyotrophic lateral sclerosis (ALS) emphasizes the crucial need to explore new and improved treatment approaches for this fatal, progressive, and disabling neurodegenerative disorder. As at the end of 2023, five treatments – riluzole, edaravone, dextromethorphan hydrobromide + quinidine sulfate (DHQ), tofersen, and sodium phenylbutyrate-tauroursodeoxycholic acid (PB-TUDCA) – were FDA approved for the treatment of patients with ALS. Among them PB-TUDCA has been shown to impact DNA processing impairments, mitochondria dysfunction, endoplasmic reticulum stress, oxidative stress, and pathologic folded protein agglomeration defects, which have been associated with ALS pathophysiology. The Phase 2 CENTAUR trial demonstrated significant impact of PB-TUDCA on the ALS Functional Rating Scale-Revised (ALSFRS-R) risk of death, hospitalization, and the need for tracheostomy or permanent assisted ventilation in patients with ALS based on post hoc analyses. More recently, contrasting with the CENTAUR trial results, results from the Phase 3 PHOENIX trial (NCT05021536) showed no change in ALSFRS-R total score at 48 weeks. Consequently, the sponsor company initiated the process with the US FDA and Health Canada to voluntarily withdraw the marketing authorizations for PB-TUDCA. In the present article, we review ALS pathophysiology, with a focus on PB-TUDCA's proposed mechanisms of action and recent clinical trial results and discuss the implications of conflicting trial data for ALS and other neurological disorders. [ABSTRACT FROM AUTHOR]

Canary seed flour is a new food ingredient that the United States Food and Drug Administration (FDA) and Health Canada recently granted Generally Regarded as Safe (GRAS) status. Stability in nutritional composition and functional properties is an essential characteristic of food ingredients for consistency in nutritional quality and performance in processing. This work assessed the effect of genotypic and environmental variation on the nutritional (protein, starch, amylose, oil, dietary fiber, minerals and fat-soluble vitamins) and pasting (as measured in viscosity (peak, trough, breakdown, final, and setback), peak time, and pasting temperatures) properties of Canary seed. The samples included four Canary seed varieties grown in randomized complete block design experiments at one location for two growing seasons. In general, the nutritional composition of Canary seed flour was not affected by genotype, growing year, and their interaction except for starch content, which was significantly affected by the growing year (p < 0.0001), and iron content, which was affected by genotypic variation (p < 0.0001). The pasting properties of Canary seed flour were significantly (p < 0.001) affected by both genotypic and growing year variation but not their interaction. Our results suggest that the food industry should measure starch and iron content prior to processing to ensure consistency in nutritional labeling. Also, for those applications where starch pasting properties are essential, the manufacturer should consider measuring the RVA pasting viscosities for every batch of raw material. The results have provided the baseline knowledge of which nutritional or functional properties of Canary seed flour can be improved through breeding and agronomy programs to ensure the reliability of Canary seed as an ingredient. [ABSTRACT FROM AUTHOR]

Introduction: The rates of gonorrhea and chlamydia have been increasing in the years preceding the COVID19 pandemic. Because most gonorrhea and chlamydia infections are located in the oropharynx and rectum for men who have sex with men (MSM), and because at-home self-collected swabs for these infections are not licensed by Health Canada or the United States Food and Drug Administration, decreased accessed to in-person care during and since the COVID19 pandemic potentially means missed case findings. Objectives: To evaluate the performance of at-home self-collected pharyngeal and rectal swabs for gonorrhea and chlamydia nucleic acid amplification testing. Methodology: All persons who contacted our Sexual Health Clinic and who had a clinical indication to complete oral and/or rectal swabs for gonorrhea and chlamydia were invited to complete at-home swabs in advance of their scheduled appointments. We mailed swabs and instructions to those who consented. Participants brought these swabs to their scheduled in clinic appointments, where we repeated the same swabs. All matching swabs were sent to the laboratory for analysis to determine concordance. Results: From September 8, 2022 to July 18, 2023, we enrolled 296 eligible participants who provided 1184 swabs. For analysis, cancelled specimens and specimens with invalid results were excluded, leaving 1032 swabs for comparison. We identified 66 STI diagnoses in 47 unique participants. Overall accuracy was high (exceeding 99%), except for rectal chlamydia, which was 96.0%. While the performance of self-swabs for chlamydia was lower compared to gonorrhea, at-home swabs identified six chlamydia infections that were missed by in-clinic collected swabs (two pharyngeal, four rectal). Removing these six cases as "false positives" increased overall accuracy for chlamydia detection to 99.7% (pharyngeal) and 97.8% (rectal). Conclusion: Self-collected at-home swabs had good performance acceptable for gonorrhea and chlamydia nucleic acid amplification testing. [ABSTRACT FROM AUTHOR]

This letter published in the Journal of General Internal Medicine discusses the therapeutic value of orphan drugs approved by Health Canada. The study compares the therapeutic benefits of orphan and non-orphan drugs for oncology and non-oncology indications. The results show no significant differences in therapeutic benefits for orphan and non-orphan drugs in oncology indications, but significant differences in various areas for non-oncology indications. The study suggests that orphan drugs may offer major therapeutic benefits for certain non-orphan indications and emphasizes the need for clear criteria and evidence generation when allocating funding for orphan drugs. [Extracted from the article]

Background: In October 2019, cannabis edibles were legalized for sale in Canada for non-medical use. This move was intended to improve public safety by regulating contents (including a maximum 10 mg tetrahydrocannabinol (THC) per package) and packaging to prevent accidental ingestion or over consumption. This study aimed to explore consumer preferences for cannabis edibles to inform cannabis policy. Methods: We explored the relative importance and trade-offs consumers make for attributes of cannabis edibles using a discrete choice experiment. Attributes included type of edible, price, THC content, cannabis taste, package information, product consistency, product recommendations, and Health Canada regulation. Participants lived in Canada, were 19 years of age or older, and purchased a cannabis edible in the last 12 months. A multinomial logit (MNL) model was used for the base model, and latent class analysis to assess preference sub-groups. This study was approved by the institutional ethics committee. Results: Among 684 participants, the MNL model showed that potency was the most relevant attribute, followed by edible type. A two-group latent class model revealed two very distinct preference patterns. Preferences for group 1 (~65% of sample) were driven primarily by edible type, while for group 2 (~35% of sample) were driven almost entirely by THC potency. Conclusion: This study found that consumer preferences for ~65% of consumers of cannabis edibles are being met through regulated channels. The remaining ~35% are driven by THC potency at levels that are not currently available on the licensed market. Attracting this market segment will require reviewing the risks and benefits of restricting THC package content. [ABSTRACT FROM AUTHOR]

E-cigarette use among youth in Canada has risen to epidemic proportions. E-cigarettes are also moderately useful smoking cessations aids. Restricting e-cigarettes to prescription only smoking cessation aids could help limit youth's access to them while keeping them available as therapies for patients who smoke conventional cigarettes. In Canada, drugs or devices must be approved by regulatory bodies such as Health Canada in order to become licensed prescription medications. A similar situation is underway in Australia, where e-cigarettes have been restricted to prescription only. This commentary explores the feasibility of a similar regulation for e-cigarettes in Canada as prescription smoking cessation aids. [ABSTRACT FROM AUTHOR]

Reactive skin decontamination lotion (RSDL) is a Health Canada approved product used by the Canadian Armed Forces for removal and inactivation of toxic chemicals on skin. Although it is considered very safe when used as directed, questions have been raised regarding whether topical RSDL in the medical setting will react exothermically with antiseptic compounds on the casualty's epidermis that could result in thermal burns. Benchtop experiments were conducted to investigate reactivity of RSDL with various antiseptic compounds or hemostatic agents. Temperature changes were closely monitored in three different volume ratios, 1:10, 1:1, and 10:1 over a time course of 16 minutes. Chlorine based bleaches versus RSDL were included as a positive control and were the only combination that exhibited a significant exothermic reaction capable of causing minor thermal burns. RSDL was also evaluated with antiseptic solution applied to swine epidermal tissue without observation of visual irritation; then in lacerated skeletal muscle tissue which resulted in no measured temperature change. The conclusion of this study is that antiseptics and hemostatic agents can be used as required on a patient decontaminated with RSDL as no exothermic reaction will occur. • RSDL does not undergo exothermic chemical reaction with antiseptics. • RSDL does not undergo exothermic chemical reaction with hemostatic agents. • Preliminary use of RSDL and antiseptic in physiological conditions do not increase risk of thermal burns. [ABSTRACT FROM AUTHOR]

Introduction: A subset of interstitial cystitis/bladder pain syndrome (IC/BPS) patients experience recurrent urinary tract infection (rUTI) associated with symptom flares. Recurrent UTI subjects with associated IC/BPS were enrolled in the first North American early clinical experience trial evaluating a new sublingual UTI preventative vaccine, MV140. It has been shown that women with rUTI develop an imbalance in the T helper 1 and 2 (Th2 over-expression) in the bladder mucosa. Our hypothesis-generating secondary analysis will suggest that this infection subcategory of IC/BPS patients develop a similar imbalance of Th1-Th2 response type to bacteria present in their urinary microbiome, leading to a bladder hypersensitivity that responds to mucosal immune modulation. Methods: Female participants with ≥3 documented UTI/year underwent a 3-month vaccination treatment period with a 9-month efficacy period after completion of vaccine treatment (total 12 months). There were no exclusion criteria for subjects in relation to baseline urinary symptoms and/or discomfort/pain. Primary outcome was no UTI following vaccination. Secondary outcomes included change in UTI incidence, overall patient-reported subjective global assessment (SGA responder defined as moderately or markedly improved on 7-point scale), and safety. Results: Sixteen subjects with IC/BPS-related symptoms and rUTI (mean age 47; range 23–74 years; mean number of UTI episodes in previous year 6.1 +/− 4.2) were eligible to be included in the Health Canada-approved MV140 vaccine study for prevention of rUTI. All subjects completed the 3-month vaccination period. One subject was lost to follow-up after their 6-month visit. Six subjects were UTI-free, while all 16 subjects had a reduction in UTI episodes compared to the year pre-vaccination. The total post-vaccination reduction in UTI episodes compared to pre-vaccination was 80% (0.1 UTI/subject/month from 0.5 UTI/subject/month, respectively). At 12 months, 13 subjects (81%) were SGA responders (moderately or markedly improved), and the responders reported a reduction in IC/BPS symptoms, with 8 subjects reporting significant or almost complete resolution of their specific long-term bladder discomfort/pain and bothersome urinary frequency or urgency. Four subjects reported mild and self-limited adverse events during vaccination period, but none were related to MV140 vaccine. Conclusion: Sublingual MV140 vaccine in IC/BPS patients with rUTI not only achieved UTI-free or reduced UTI incidence status but also, after approximately 9 months post vaccination, resolution of patients' long-term treatment-refractory IC/BPS symptoms. This suggests some cases of IC/BPS may be etiologically based on Th2-driven hypersensitivity to bacteria within or entering the urinary microbiome that responds to a vaccine whose mechanism of action is to normalize or balance the bladder Th1/Th2 mucosal immune system. [ABSTRACT FROM AUTHOR]

In the event of a widespread radiological incident, thousands of individuals will require rapid assessment of exposure using validated biodosimetry assays to inform clinical triage. In this scenario, multiple biodosimetry laboratories may be necessary for large-volume sample processing. To meet this need, we have developed a high-throughput assay for the rapid measurement of intracellular protein biomarkers in human peripheral blood samples using an Imaging Flow Cytometry (IFC) platform. The objective of this work was to harmonize and validate the reproducibility of our blood biomarker assay for radiation exposure across three IFC instruments, two located at Columbia University (CU) and the third at Health Canada. The Center for Radiological Research (CRR) at CU served as the central laboratory and reference instrument, where samples were prepared in triplicate, labeled with two radiation responsive leukocyte biomarkers (BAX and phosphor-p53 (Ser37)), and distributed for simultaneous interrogation by each IFC. Initial tests showed that significantly different baseline biomarker measurements were generated on each instrument when using the same acquisition settings, suggesting that harmonization of signal intensities is necessary. Subsequent tests harmonized biomarker measurements after irradiation by modulating laser intensity using two reference materials: unstained samples and standardized rainbow beads. Both methods generated measurements on each instrument without significant differences between the new and references instruments, allowing for the use of one master template to quantify biomarker expression across multiple instruments. Deming regression analyses of 0–5 Gy dose-response curves showed overall good correlation of BAX and p53 values across new and reference instruments. While Bland-Altman analyses indicated low to moderate instrument biases, ROC Curve analyses ultimately show successful discrimination between exposed and unexposed samples on each instrument (AUC values > 0.85). [ABSTRACT FROM AUTHOR]

Salmonellosis is one of the leading causes of gastrointestinal infections in humans. In Canada, it is estimated that approximately 87,500 cases of salmonellosis occur every year in humans, resulting in 17 deaths. In the United States, it is estimated that 26,500 hospitalizations and 420 deaths occur every year. In dairy cattle, infections caused by nontyphoidal Salmonella enterica can cause mild to severe disease, including enteritis, pneumonia, and septicemia. Our study objectives were to determine the proportion of fecal samples positive for Salmonella in dairy cattle in Canada and determine the resistance pattern of these isolates. We used data collected through the Canadian Dairy Network for Antimicrobial Stewardship and Resistance (CaDNetASR). Pooled fecal samples from preweaning calves, postweaning heifers, lactating cows, and manure storage were cultured for Salmonella, and the isolates were identified using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Antimicrobial susceptibilities were determined using the minimum inhibitory concentration test, and resistance interpretation was made according to the Clinical and Laboratory Standards Institute. A 2-level, multivariable logistic regression model was built to determine the probability of recovering Salmonella from a sample, accounting for province, year, and sample source. The proportion of farms with at least one positive sample were 12% (17/140), 19% (28/144), and 17% (24/144) for the sampling years 2019, 2020, and 2021, respectively. Out of the 113 Salmonella isolates, 23 different serovars were identified. The occurrence of Salmonella appeared to be clustered by farms and provinces. The most common serovars identified were Infantis (14%) and Typhimurium (14%). Overall, 21% (24/113) of the Salmonella isolates were resistant to at least one antimicrobial. Resistance to tetracycline was commonly observed (17%); however, very limited resistance to category I antimicrobials (categorization according to Health Canada that includes third-generation cephalosporins, fluoroquinolones, polymyxins, and carbapenems) was observed, with one isolate resistant to amoxicillin and clavulanic acid. The proportion of Salmonella isolates resistant to 2 and 3 antimicrobial classes was 3.5% and 8.8%, respectively. Our study provided valuable information on the proportion of fecal samples positive for Salmonella , the serovars identified, and the associated resistance patterns across CaDNetASR herds, at regional and national levels. [ABSTRACT FROM AUTHOR]

[177Lu]Lu-PSMA-617 has recently been successfully approved by the FDA, the MHRA, Health Canada and the EMA as Pluvicto®. However, salivary gland (SG) and kidney toxicities account for its main dose-limiting side-effects, while its corresponding uptake and retention mechanisms still remain elusive. Recently, the presence of different ATP-binding cassette (ABC) transporters, such as human breast cancer resistance proteins (BCRP), multidrug resistance proteins (MDR1), multidrug-resistance-related proteins (MRP1, MRP4) and solute cassette (SLC) transporters, such as multidrug and toxin extrusion proteins (MATE1, MATE2-K), organic anion transporters (OAT1, OAT2v1, OAT3, OAT4) and peptide transporters (PEPT2), has been verified at different abundances in human SGs and kidneys. Therefore, our aim was to assess whether [177Lu]Lu-PSMA-617 and [225Ac]Ac-PSMA-617 are substrates of these ABC and SLC transporters. For in vitro studies, the novel isotopologue ([α,β-3H]Nal)Lu-PSMA-617 was used in cell lines or vesicles expressing the aforementioned human ABC and SLC transporters for inhibition and uptake studies, respectively. The corresponding probe substrates and reference inhibitors were used as controls. Our results indicate that [177Lu]Lu-PSMA-617 and [225Ac]Ac-PSMA-617 are neither inhibitors nor substrates of the examined transporters. Therefore, our results show that human ABC and SLC transporters play no central role in the uptake and retention of [177Lu]Lu-PSMA-617 and [225Ac]Ac-PSMA-617 in the SGs and kidneys nor in the observed toxicities. [ABSTRACT FROM AUTHOR]

Maskwio'mi (Mi'kmaw language for "oil made from birch bark") is a traditional topical skin medicine of the Mi'kmaq people of Atlantic Canada and is produced in a torrefaction process by heating birch bark (Betula papyrifera, paper birch) inside a metal container in a fire. The resulting viscous, oily mixture is traditionally mixed with goose fat or bear grease to create a topical salve that is subsequently applied to affected skin areas. When birch bark is exposed to high temperatures, pyrolytic chemical processes produce a complex mixture of pharmacologically active compounds, including potentially harmful side products such as ortho-, meta-, and para-cresol. This study discusses the qualitative and quantitative GC-MS analysis of cresols found in maskwio'mi and the challenges of the complex organic matrix. Using caffeine as an internal standard, ortho-, meta-, and para-cresol in birch bark extract were determined to be in the approximate order of 50–1500 ppm range with 3.24 ± 0.09 × 102 ng mg−1 (324 ppm), 8.7 ± 1.0 × 102 ng mg−1 (87 ppm), and 12.4 ± 1.6 × 102 ng mg−1 (1240 ppm), respectively, and thus suitable by Health Canada and FDA cosmetics regulation standards when the extract is co-formulated in creams to concentrations of 0.1–5 wt.% for topical use. [ABSTRACT FROM AUTHOR]

Two prefusion F protein-based vaccines, Arexvy and Abrysvo, have been approved by Health Canada for protecting older adults against respiratory syncytial virus (RSV)-associated lower respiratory tract disease. We estimated the health benefits and cost-effectiveness of these vaccines under a publicly funded single-dose vaccination program in Ontario that targets residents of long-term care homes (LTCHs). Additionally, we evaluated an extended program that broadens vaccination to include community-dwelling older adults. A discrete-event simulation model was parameterised with the burden of RSV disease including outpatient care, hospitalisation, and death among adults aged 60 years or older in Ontario, Canada. Accounting for direct and indirect costs (in 2023 Canadian dollars) associated with RSV-related outcomes, we calculated the net monetary benefit using quality-adjusted life-year (QALY) gained, and determined the range of price-per-dose (PPD) for vaccination programs to be cost-effective from both healthcare and societal perspectives over two RSV seasons. The incremental cost-effectiveness ratio (ICER) was calculated to estimate the additional costs required to gain one QALY. Using a willingness-to-pay of $50,000 per QALY gained, we found that vaccinating 90% of residents in LTCHs with Arexvy would be cost-effective from a societal perspective for a PPD up to $163, producing a mean ICER value of $49,984 (95% CI: $47,539 to $52,704) per QALY gained with a two-year budget impact of $463,468 per 100,000 older adults. The reduction of hospitalizations was estimated at 7.0% compared to the no-vaccination scenario. Extending the program to include community-dwelling older adults with a 74% coverage akin to influenza vaccination, Arexvy remains cost-effective for a PPD up to $139, with a mean ICER value of $49,698 (95% CI: 48,022 to 51,388) per QALY gained and a two-year budget impact of $8.63 million. Compared to the no-vaccination scenario, the extended program resulted in a 57.3% reduction in RSV-related hospitalisations. Vaccinating residents of LTCHs against RSV disease would be cost-effective depending on PPD; extending the program to community-dwelling older adults would provide substantial health benefits, averting significant direct healthcare costs and productivity losses. [ABSTRACT FROM AUTHOR]

Consumption of cosmetic products in daily life in order to improve skin quality or appearance is becoming quite common. Over time, it may expose consumers to skin problems and effects caused by the absorption of chemical elements. Clean cosmetic production is important for our health. However, heavy metals can be found as impurities in raw materials or as by-products of the cosmetic production process. Women's ingestion and exposure to organic and inorganic contaminants in cosmetics through dermal absorption, due to reasons such as personal habits and characteristics of the living environment, may contribute to carcinogenic risks following daily dietary exposure. NCS ZC 81002b (Human Hair) was performed as a certified reference material in method validation. This work was conducted to evaluate element concentrations of selected elements (Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Hg, Cd and Pb) in 3 different brands of children's cosmetic products such as bright and colorful 22 eye shadows (7 different colour) 4 lipsticks (3 different colour) and 4 nail polishes (3 different colour) used by children in Turkey. The sample solutions were analyzed with the inductively coupled plasma mass spectrometry (ICP-MS) technique after the microwave digestion system. Consequently, the highest concentration of Al used as pigment was found in the eye shadow, lipstick and nail polish samples for the 3 brands, while the Se concentrations were the lowest in lipstick samples. The results of As, Cd, Hg, Pb, which are restricted or banned for use in cosmetic products in most countries, are below the limits set by the Food and Drug Administration (FDA) and Health Canada Product Safety Laboratory (PSL). [ABSTRACT FROM AUTHOR]

New sources of proteins are essential to meet the demands of the growing world population and evolving food trends. Assessing the allergenicity of proteins in novel food (NF) poses a significant food safety regulatory challenge. The Codex Alimentarius Commission presented an allergenicity assessment protocol for genetically modified (GM) foods, which can also be adapted for NF. Since no single laboratory test can adequately predict the allergenic potential of NF, the protocol follows a weight‐of‐evidence approach, evaluated by experts, as part of a risk management process. Regulatory bodies worldwide have adopted this safety protocol, which, among other things, promotes global harmonization. This review unravels the reliability and various motivations, terms, concepts, and approaches of allergenicity assessments, aiming to enhance understanding among manufacturers and the public. Health Canada, Food Safety Commission JAPAN, and Food Standards Australia New Zealand were surveyed, focusing on the European Food Safety Authority and the US Food Safety Administration for examples of scientific opinions regarding allergenicity assessments for novel and GM foods, from 2019 to 2023. According to our findings, current regulatory allergenicity assessments for NF approval primarily rely on literature reviews. Only a few of the NF assessments proactively presented additional tests. We recommend conducting bioinformatic analyses on NF when a panel of experts deems that there is insufficient prior scientific research. [ABSTRACT FROM AUTHOR]

The present study was conducted to investigate the concentration of nitrate in drinking water resources and its carcinogenic risk in the southern provinces of Iran in 2020. Raw data of nitrate concentrations were obtained from wastewater and water Company of each province, and Mont Carlo Simulation (MCS) was considered 10‐5 for estimating human carcinogenic risk. Our results demonstrated that in the drinking water resources of Khuzestan and Fars provinces, the nitrate level was 59 and 72 mg/L, respectively, higher than the World Health Organization (WHO) recommendation. The calculated carcinogenic risk of nitrate for Khuzestan and Fars provinces were higher than the range set by WHO and Health Canada, 8.8 × 10−5 and 1.3 × 10−5, respectively. Exposure to an unacceptable nitrate level through drinking water can affect blood carrying oxygen and cause methemoglobinemia and a significant relationship with gastrointestinal cancer spread. [ABSTRACT FROM AUTHOR]

Background: Hereditary angioedema due to C1 inhibitor deficiency is a rare genetic condition that causes recurrent swelling with consequent functional impairment and decreased quality of life. Long-term prophylaxis (LTP) to prevent angioedema episodes is a key component of disease management. Berotralstat, an oral, once-daily plasma kallikrein inhibitor, was approved for LTP by Health Canada in 2022. Methods: We conducted a retrospective, real-world study investigating the effectiveness and adverse effects of berotralstat. Data on angioedema frequency, disease control, and adverse events were tabulated. Patient satisfaction with treatment was scored on a 5-point Likert scale, with 1 representing very unsatisfied and 5 representing very satisfied with therapy. Results: From June, 2022 and May, 2023, 8 patients with HAE type 1 or type 2 received berotralstat. Effectiveness data were available for 7 patients who continued the drug for at least 3 months, 4 of whom switched to berotralstat from plasma-derived C1 inhibitor LTP. In these 7 patients, the average number of attacks per month decreased from 3.3 to 1.6 (p<0.05), representing a ~52% reduction in attack frequency. Median angioedema control test score numerically improved from 8 to 13 (p=0.0781). Of the 8 patients who received berotralstat, 3 reported no adverse effects and 5 experienced gastrointestinal side effects, which were mild and transient in 3 and led to discontinuation in 1. Average treatment satisfaction was between satisfied and very satisfied at 4.3. Conclusion: Berotralstat is an effective agent for long-term prophylaxis in HAE. Most patients experienced no adverse effects or mild, transient gastrointestinal symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is one of the most important, modifiable risk factors for cardiovascular disease. The popularity of wearable devices provides an opportunity to test whether device guided slow mindful breathing may serve as a non-pharmacological treatment in the management of hypertension. Methods: Fitbit Versa-3 and Sense devices were used for this study. In addition, participants were required to own an FDA or Health Canada approved blood pressure measuring device. Advertisements were shown to 655,910 Fitbit users, of which 7,365 individuals expressed interest and filled out the initial survey. A total of 1,918 participants entered their blood pressure readings on at least 1 day and were considered enrolled in the study. Participants were instructed to download a guided mindful breathing app on their smartwatch device, and to engage with the app once a day prior to sleep. Participants measured their systolic and diastolic blood pressure prior to starting each mindful breathing session, and again after completion. All measurements were self reported. Participants were located in the United States or Canada. Results: Values of systolic and diastolic blood pressure were reduced following mindful breathing. There was also a decrease in resting systolic and diastolic measurements when measured over several days. For participants with a systolic pressure ≥ 130 mmHg, there was a decrease of 9.7 mmHg following 15 min of mindful breathing at 6 breaths per minute. When measured over several days, the resting systolic pressure decreased by an average of 4.3 mmHg. Discussion: Mindful breathing for 15 min a day, at a rate of 6 breaths per minute is effective in lowering blood pressure, and has both an immediate, and a short term effect (over several days). This large scale study demonstrates that device guided mindful breathing with a consumer wearable for 15 min a day is effective in lowering blood pressure, and a helpful complement to the standard of care. [ABSTRACT FROM AUTHOR]

Background: Dupilumab is approved for moderate‐severe atopic dermatitis (AD) in patients aged ≥6 months by the US Food and Drug Administration and Health Canada; however, there are little real‐world data because providers have limited practical experience with this recently approved therapy. Objectives: To describe the real‐world effectiveness and safety in patients aged <12 years with moderate‐severe AD currently receiving or previously having received dupilumab. Methods: A multicenter retrospective study was conducted at six Canadian sites. Cases were divided into Group 1 ≤2 years old, Group 2 >2 to <6 years old, and Group 3 ≥6 to <12 years old. Medical history and details of dupilumab treatment were collected. The primary outcome was to measure the improvement in eczema area and severity index. Secondary outcomes examined included the children's dermatology life quality index/infant's dermatitis quality of life, peak pruritus numerical rating scale, and delay to dupilumab access for patients who were considered off‐label for dupilumab due to their age. Results: Sixty three pediatric patients (37 males) with moderate‐to‐severe AD were included; the mean age was 6.4 years old (range: 2–11) when dupilumab treatment was started. Overall, 75% (36/48) achieved EASI‐75% and 71% (34/48) achieved EASI‐90. EASI‐75 and EASI‐90 were achieved in 90% (17/19) and 73% (12/19) in patients <6 years old, and 76% (22/29) and 59% (17/29) in patients >6 years old, respectively. No serious adverse events were reported. Conclusions: Dupilumab is safe and effective for patients under the age of 12. However, even for experienced providers, access to the medication was challenging. [ABSTRACT FROM AUTHOR]

Background: To curb the growing impact of drug shortages, Health Canada developed the Tiered Notification and Communication Framework which assigns potential shortages a corresponding tiered status. Tier-3 is assigned to shortages with the greatest potential impact on the healthcare system. This study aims to describe drug purchasing trends in response to Tier-3 shortages using three case-examples. Methods: We conducted a time-series analysis of monthly purchasing data for three out of 17 Tier-3 drug shortages (hydralazine, sarilumab, and medroxyprogesterone acetate) with publicly available reports in July 2021 and available IQVIA MIDAS data from January 2016 to December 2021. We assessed percent changes in purchasing at 1-, 3-, and 6-months after the onset of each Tier-3 drug shortage and interventional ARIMA modelling was used to assess the statistical significance. Results: Medroxyprogesterone acetate experienced a significant shift (p = 0.0370) in purchasing following its shortage, and the 1-, 3-, and 6-month percent changes were +14.9%, +6.8% and -3.1%, respectively. Hydralazine and sarilumab did not show a significant shift. The 1-, 3-, and 6-month percent changes for hydralazine were +15.5%, +10.2%, and +9.6% respectively and +25.2%, +45.1% and +39.2 for sarilumab. Conclusions: These results indicate that drugs assigned a Tier-3 status may not show declines in purchasing in the months following status assignment, which may be due to policy responses following the assignment. However, more insight is needed into the mechanisms through which these policy measures impact shortages and whether they are functioning as intended. [ABSTRACT FROM AUTHOR]

• Health Canada's Fixed Point Surveillance network can respond to cosmic radiation. • Forbush decrease events and the GLE69 event have been observed in the network. • The network response to these events is similar to the global muon/neutron detectors. • The network is readily available for real-time space weather monitoring. This work presents a feasibility study of utilizing Health Canada's terrestrial radiation monitoring network, the Fixed Point Surveillance (FPS) network, for space weather monitoring through demonstrating detections of Forbush decrease and ground level enhancement events. The network is currently comprised of more than eighty sodium iodide spectrometers distributed across Canada. It was designed for terrestrial radiation monitoring but is also capable of registering cosmic radiation in a high-energy channel. Data from fourteen FPS stations for the period from 2003 to 2018 were analyzed and compared with data obtained by other ground-level cosmic radiation monitoring systems. The level of atmospheric impacts on measurements can be well explained, and signatures of both long-term solar cycle variations and sporadic solar events have been detected in the FPS network. The Forbush decrease amplitudes in FPS were found to be comparable to those obtained in the global muon detector network but about 2–3 times lower than those recorded by the global neutron monitoring network. This study suggests that the 20 years of cosmic ray data from the FPS network can be used for climatological space weather studies. In addition, the network can be readily available for real-time space weather monitoring. [ABSTRACT FROM AUTHOR]

Boronic acids/esters have recently emerged in the field of medicinal and pharmaceutical research due to their exceptional oxophilicity, low toxicity, and unique structure. They are known as potent enzyme inhibitors, cancer therapy capture agents, and can mimic certain types of antibodies to fight infections. They have been designed and developed into drugs, and this approach has emerged in the last 20 years. Five boronic acid drugs have been approved by the FDA and Health Canada, two of which are used to treat cancer, specifically multiple myeloma. The purpose of this review is to investigate boronic acid/ester derivatives as potential pharmaceutical agents as well as the mechanism of action. It will concentrate on six types of cancer: multiple myeloma, prostate cancer, breast cancer, lung cancer, cervical cancer, and colon cancer. Some newly developed boron-containing compounds have already demonstrated highly promising activities, but further investigation is required before final conclusions can be drawn. [ABSTRACT FROM AUTHOR]

Background: Globally, pharmaceutical companies offer patient support programs in tandem with their products, which aim to enhance medication adherence and patient experience through education, training, support and financial assistance. We sought to identify the proportion and characteristics of such patient support programs in Canada and to describe the nature of supports provided. Methods: We conducted a crosssectional study to identify and characterize all marketed prescription drugs available in Canada as of Aug. 23, 2022, using the Health Canada Drug Product and CompuScript databases. To describe the nature of supports provided, we conducted a content analysis of publicly available patient support program websites and Web-based documents. Using logistic regression, we identified characteristics of drugs associated with having a patient support program including brand-name or branded generic (generic medications with a proprietary name), orphan (medications for rare diseases) or biologic drug status; estimated total cost of prescriptions dispensed at retail pharmacies; and price per unit. Results: Of the 2556 prescription drugs marketed by 89 companies in the study period, 256 (10.0%) had a patient support program in Canada. Many of the 89 drug manufacturers (n = 55, 61.8%) offered at least 1 patient support program, frequently relying on third-party administrators for delivery. Brandname and branded generic medications, biologic agents and drugs with orphan status were more likely to have a patient support program than generic drugs. Compared with drugs priced $1.01–$10.00 per unit, drugs priced $10.01–$100.00 per unit were nearly 8 times more likely to have a patient support program (adjusted odds ratio 7.54, 95% confidence interval 4.07– 14.64). Most sampled patient support programs included reimbursement navigation (n = 231, 90.2%) and clinical case management (n = 223, 87.1%). Interpretation: About 1 in 10 drugs marketed in Canada has a manufacturersponsored patient support program, but these are concentrated around brand-name, branded generic, biologic and high-cost drugs, often for rare diseases. To understand the impact of patient support programs on health outcomes and sustainable access to cost-effective medicines, greater transparency and independent evaluation of patient support programs is necessary. [ABSTRACT FROM AUTHOR]

The number of cigarette capsule users is increasing; however, a comprehensive epidemiological investigation comparing the harmfulness of capsule and non-capsule cigarettes, particularly concerning the composition of flavor components and mainstream smoke, is lacking. The present study aimed to investigate the effect of capsule burst on the compound composition of mainstream smoke by quantifying the Hoffmann list and flavor (geraniol, eugenol, menthofuran, and pulegone) in mainstream smoke with and without crushing the capsules. The findings indicate that while tar values tended to increase when the capsules were burst, there was no significant change observed in the other Hoffmann list components, such as nicotine, benzo[α]pyrene, tobacco-specific nitrosamines, aromatic amines, and phenolics. However, when the capsules burst, menthofuran and pulegone, which were present in the capsule and could cause toxicity, were found in the mainstream smoke via the International Standard Organization (1.5–4.0 μg/cig and 5.13–6.00 μg/cig smoking regime) and Health Canada Intense (12.8–18.2 μg/cig and 22.77–24.67 μg/cig smoking regime). Therefore, understanding the capsule composition is important, as the toxic components of the capsules can be inhaled as smoke, posing a potential health risk. [ABSTRACT FROM AUTHOR]

Heavy metal pollution in agricultural soil is a threat to people's health and sustainable development. However, there is currently no nationwide health risk assessment in China. In this study, we performed a preliminary assessment of heavy metals in agricultural soils of the Chinese mainland, and found obvious carcinogenic risks (total lifetime carcinogenic risk (TLCR) > 1 × 10–5). A similar spatial distribution pattern was found in soil heavy metal and the mortality of esophagus and stomach cancers. Combining the potential carcinogenic risk assessed by LCR for individual heavy metal with Pearson correlation, Geographical Detector (q statistic > 0.75 for TLCR, p < 0.05), and redundancy analysis (RDA), it was found that long-term exposure and intake route of heavy metals exceeding the maximum safety threshold (Health Canada standard) may induce digestive system (esophagus, stomach, liver, and colorectum) cancers in rural populations. Through Partial Least Squares Path Model (PLS-PM), it was also revealed that the LCR of heavy metals was closely related to the soil environmental background (path coefficients = 0.82), which in turn was affected by factors such as economic development and pollution discharge. The current research results highlight the potential carcinogenic risk to the digestive system associated with low-dose and long-term exposure to heavy metals in agricultural soils, and policymakers should propose countermeasures and solutions according to the local conditions. [ABSTRACT FROM AUTHOR]

This study investigates the ex‐ante effects of the front‐of‐package (FoP) nutrition labeling for food products high in saturated fat, sugar, and/or sodium, which is a new regulation recently announced by Health Canada to combat obesity. The Canadian food industry has until January 1, 2026, to comply with the new regulations. To examine the ex‐ante effects of this policy, an incentivized experiment is conducted in a lab that replicates a grocery store. The results at the product level indicate a significant decrease in the probability of choosing a product with a "high in" label compared to those without "high in" labels. Basket‐level results demonstrate that FoP labeling is significantly associated with a lower quantity share and dollar value share of products high in one of the mentioned nutrients selected in a grocery basket, as well as fewer grams of sugar and sodium in a grocery basket. Furthermore, the study reveals that individuals with higher educational attainment, a risk‐averse nature, and a lower level of self‐reported nutrition knowledge tend to react more to the labeling. The insights from eye‐tracking data further support these results, revealing that product choices are deterred by a fixation on "high in" labels. This study contributes to an improved understanding of the pathway in which labeling schemes influence food choices. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the association between past infertility and the type and timing of menopause in midlife women? SUMMARY ANSWER Women with a history of infertility were more likely to experience surgical menopause overall and had elevated risk of earlier surgical menopause until age 43 years but experienced no differences in the timing of natural menopause. WHAT IS KNOWN ALREADY Infertility is experienced by 12–25% of women and is thought to reveal a propensity for poor health outcomes, such as chronic illness, later in life. However, little is known about whether infertility is linked with characteristics of the menopausal transition as women age, despite possible shared underlying pathways involving ovarian function and gynecologic disease. STUDY DESIGN, SIZE, DURATION Secondary analysis of a prospective cohort study of 13 243 midlife females recruited in Phase 1 of the Alberta's Tomorrow Project (Alberta, Canada) and followed approximately every 4 years (2000–2022). PARTICIPANTS/MATERIALS, SETTING, METHODS Data were collected through standardized self-report questionnaires. History of infertility, defined as ever trying to become pregnant for more than 1 year without conceiving, was measured at baseline. Menopause characteristics were measured at each study follow-up. Menopause type was defined as premenopause, natural menopause, surgical menopause (bilateral oophorectomy), or indeterminate menopause (premenopausal hysterectomy with ovarian conservation). Timing of natural menopause was defined as the age at 1 full year after the final menstrual period, and timing of surgical and indeterminate menopause was defined as the age at the time of surgery. We used flexible parametric survival analysis for the outcome of menopause timing with age as the underlying time scale and multinomial logistic regression for the outcome of menopause type. Multivariable models controlled for race/ethnicity, education, parity, previous pregnancy loss, and smoking. Sensitivity analyses additionally accounted for birth history, menopausal hormone therapy, body mass index, chronic medical conditions, and age at baseline. MAIN RESULTS AND THE ROLE OF CHANCE Overall, 18.2% of women reported a history of infertility. Past infertility was associated with earlier timing of surgical menopause exclusively before age 43 years (age 35: adjusted hazard ratio 3.13, 95% CI 1.95–5.02; age 40: adjusted hazard ratio 1.83, 95% CI 1.40–2.40; age 45: adjusted hazard ratio 1.13, 95% CI 0.87–1.46) as well as greater odds of experiencing surgical menopause compared to natural menopause (adjusted odds ratio 1.40, 95% CI 1.18–1.66). Infertility was not associated with the timing of natural or indeterminate menopause. LIMITATIONS, REASONS FOR CAUTION Information on the underlying cause of infertility and related interventions was not collected, which precluded us from disentangling whether associations differed by infertility cause and treatment. Residual confounding is possible given that some covariates were measured at baseline and may not have temporally preceded infertility. WIDER IMPLICATIONS OF THE FINDINGS Women with a history of infertility were more likely to experience early surgical menopause and may therefore benefit from preemptive screening and treatment for gynecologic diseases to reduce bilateral oophorectomy, where clinically appropriate, and its associated health risks in midlife. Moreover, the lack of association between infertility and timing of natural menopause adds to the emerging knowledge that diminishing ovarian reserve does not appear to be a primary biological mechanism of infertility nor its downstream implications for women's health. STUDY FUNDING/COMPETING INTEREST(S) Alberta's Tomorrow Project is only possible due to the commitment of its research participants, its staff and its funders: Alberta Health, Alberta Cancer Foundation, Canadian Partnership Against Cancer and Health Canada, and substantial in-kind funding from Alberta Health Services. The views expressed herein represent the views of the author(s) and not of Alberta's Tomorrow Project or any of its funders. This secondary analysis is funded by Project Grant Priority Funding in Women's Health Research from the Canadian Institutes of Health Research (Grant no. 491439). N.V.S. is supported by a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research. H.K.B. is supported by the Canada Research Chairs Program. E.A.B. is supported by an Early Career Investigator Award in Maternal, Reproductive, Child and Youth Health from the Canadian Institutes of Health Research. A.K.S. has received honoraria from Pfizer, Lupin, Bio-Syent, and Eisai and has received grant funding from Pfizer. N.V.S. H.K.B. and E.A.B. have no conflicts of interest to report. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic led to major changes in public policies to address supply chain disruption and escalated the price of consumer disinfectant products. To address market demands on alcohol‐based hand rubs and disinfectants, Health Canada implemented major changes to the regulations regarding composition, handling, transportation, and packaging to insure product availability. Furthermore, accelerated licensing of ingredients and packaging did not meet standard medical quality guidelines yet were authorized for manufacturing and packaging of alcohol‐based hand rubs and disinfectants. The accountability associated with these policy changes were reactive, including industry self‐reporting, consumer reporting, and Health Canada advisories and recalls that were responsive to products after they were available in the market. Nonetheless, Canadian public health policy increased hand sanitizers availability. However, some of the interim policies have raised major public health concerns associated with ethanol quality, packaging, and labeling, and enforcement of regulations. In this paper, we review the changes in the Canadian regulations amid the current pandemic and we evaluate the unintended health risks that might arise from these changes. [ABSTRACT FROM AUTHOR]

With the recent Health Canada approval of olaparib for high-risk, HER2-negative early breast cancer, physicians are now facing the practical challenges of integrating olaparib into current management of triple-negative breast cancer (TNBC) and HR-positive, HER2-negative (HR+/HER2−) early breast cancer. This review provides perspectives on some of the challenges related to identification of olaparib candidates, with a focus on the latest guidance for germline BRCA testing and considerations regarding high-risk disease definitions. Updated treatment pathways are explored for both disease states, including other adjuvant treatment options such as pembrolizumab, capecitabine, and abemaciclib. Gaps in the current literature regarding the sequential or combined use of these adjuvant therapies are noted and future, potentially informative, studies are briefly examined. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is one of the leading causes of death in Canada and worldwide, and there is ongoing discovery of new cancer medicines. However, before these drugs are publicly funded, they undergo a rigorous review process. In a single-payer health system, additional reviews are necessary to balance clinical benefit with cost effectiveness, which can cause delays in the public availability of these lifesaving treatments. Our study aimed to examine the factors that impact these drug review times and, ultimately, public funding recommendations. Interestingly, we found that longer drug review times (time from Health Canada approval to pCODR final recommendations) were associated with negative funding recommendations, with drugs for lung and gastrointestinal cancers undergoing more lengthy review processes. New oncology drugs undergo detailed review prior to public funding in a single-payer healthcare system. The aim of this study was to assess how cancer drug review times impact funding recommendations. Drugs reviewed by the pan-Canadian Oncology Drug Review (pCODR) between the years 2012 and 2020 were included. Data were collected including Health Canada approval dates, initial and final funding recommendations, treatment intent, drug class, clinical indications, and incremental cost-effectiveness ratios (ICER). Univariable and multivariable analyses were used to determine the association between funding recommendations and review times. Of the 164 applications submitted, 130 received a positive final recommendation. Median time from Health Canada (HC) approval to final recommendation was longer for drugs indicated for the treatment of gastrointestinal (GI) and lung cancer compared to breast, genitourinary (GU), and other tumours (205 vs. 198 vs. 111 vs. 129 vs. 181 days, respectively; Kruskal–Wallis p = 0.0312). Drugs with longer review times were more likely to receive a negative pCODR recommendation, even when adjusting for tumour type, drug class, and intent of therapy (157 vs. 298 days; Wilcoxon p = 0.0003, OR 1.002 95% CI [1.000–1.004].). There was no association between funding recommendation and tumour type or class of drug. The exploration of factors associated with variance in review times will be important in ensuring timely patient access to cancer drugs. [ABSTRACT FROM AUTHOR]

Purpose: The National Institutes of Health's policy for the inclusion of females in clinical research was a pivotal step towards the consideration of sex as a biological variable, which is of particular importance in oncology, given differential incidence and outcomes of cancer between the sexes, and known pharmacodynamic, pharmacokinetic, and immunological differences. Therefore, we aim to investigate if such biological sex-based differences translate to clinically meaningful outcome differences from recently approved systemic oncology therapies. Methods: A systematic review of randomized control trials (RCTs) cited in Food and Drug Administration, European Medicines Agency, and Health Canada approvals was conducted. Chemotherapy, targeted agents, and immunotherapy RCTs reporting sex-based sub-group analyses for overall/progression-free survival (OS/PFS) were considered. Hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized. Sensitivity analyses for survival endpoints, drug type, and cancer site were conducted. Results: Ninety-nine RCTs were included, representing 62,384 patients (23,574 (38%) female). Pooled OS HRs [95% CIs] were 0.77 [0.72–0.81] and 0.76 [0.72–0.79] for females and males, respectively (P = 0.73), and 0.51 [0.47–0.56] and 0.57 [0.53–0.61] (P = 0.08) for PFS. Sensitivity analyses yielded similar results. No RCTs reported sex-based toxicity or quality-of-life (QOL) data. Conclusion: Female and male patients appear to derive comparable benefits from recently approved systemic oncology therapies. Future RCTs are encouraged to report sex-based toxicity and QOL data. [ABSTRACT FROM AUTHOR]

Activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS), in particular, a point mutation leading to a glycine-to-cysteine substitution at codon 12 (G12C), are among the most frequent genomic alterations in non-small cell lung cancer (NSCLC). Several agents targeting KRAS G12C have recently entered clinical development. Sotorasib, a first-in-class specific small molecule that irreversibly inhibits KRAS G12C, has since obtained Health Canada approval. The emergence of novel KRAS-targeted therapies warrants the development of evidence-based consensus recommendations to help clinicians better understand and contextualize the available data. A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on recommendations for the treatment of advanced KRAS G12C-mutated NSCLC. The panel agreed that testing for KRAS G12C should be performed as part of a comprehensive panel that includes current standard-of-care biomarkers. Sotorasib, the only approved KRAS G12C inhibitor in Canada, is recommended for patients with advanced KRAS G12C-mutated NSCLC who progressed on guideline-recommended first-line standard of care for advanced NSCLC without driver alterations (immune-checkpoint inhibitor(s) [ICIs] +/− chemotherapy). Sotorasib could also be offered as second-line therapy to patients who progressed on ICI monotherapy that are not candidates for a platinum doublet and those that received first-line chemotherapy with a contraindication to ICIs. Preliminary data indicate the activity of KRAS G12C inhibitors in brain metastases; however, the evidence is insufficient to make specific recommendations. Regular liver function monitoring is recommended when patients are prescribed KRAS G12C inhibitors due to risk of hepatotoxicity. [ABSTRACT FROM AUTHOR]

The pharmaceutical industry's promotion of opioids in North America has been well-documented. Yet despite the clear consequences of improperly classifying pharmaceutical company messaging and frequently permissive approaches that allow the pharmaceutical industry to self-regulate its own advertising, there has been scarce investigation to date of how pharmaceutical industry stakeholders interpret definitions of "advertising." This study explores how variations of "marketing" and "advertising" are strategically framed by the different actors involved in the manufacturing and distribution of pharmaceutical opioids. We employed a framing analysis of industry responses to Health Canada's letter to Canadian manufacturers and distributors of opioids requesting their commitment to voluntarily cease all marketing and advertising of opioids to health care professionals. Our findings highlight companies' continuing efforts to frame their messaging as "information" and "education" rather than "advertising" in ways that serve their interests. This study also calls attention to the industry's continual efforts to promote self-regulation and internal codes of conduct within a highly permissive federal regulatory framework with little concern for violations or serious consequences. While this framing often occurring out of public sight, this study highlights the subtle means through which the industry attempts to frame their promotion strategies away from "marketing". These framing strategies have significant consequences for the pharmaceutical industry's capacity to influence healthcare professionals, patients, and the general public. [ABSTRACT FROM AUTHOR]

Background: In May 2022, Health Canada approved a three-year exemption from the Controlled Drugs and Substances Act decriminalizing possession of certain illegal substances for personal use among adults in the province of British Columbia. The exemption explicitly includes a cumulative threshold of 2.5 g of opioids, cocaine, methamphetamine, and MDMA. Threshold quantities are commonly included in decriminalization policies and justified within law enforcement systems to delineate personal use among people who use drugs versus drug dealers who are carrying for trafficking purposes. Understanding the impact of the 2.5g threshold can help define the extent to which people who use drugs will be decriminalized. Methods: From June-October 2022, 45 people who use drugs from British Columbia were interviewed to gain an understanding of their perceptions on decriminalization, particularly on the proposed threshold of 2.5 g. We conduced descriptive thematic analyses to synthesize common interview responses. Results: Results are displayed under two categories: 1) Implications for substance use profiles and purchasing patterns, including implications on the cumulative nature of the threshold and impacts on bulk purchasing, and 2) Implications of police enforcement, including distrust of police use of discretion, potential for net widening and jurisdictional discrepancies in enforcing the threshold. Results illustrate the need for the decriminalization policy to consider diversity in consumption patterns and frequency of use among people who use drugs, the inclination to purchase larger quantities of substances for reduced costs and to guarantee a safe and available supply, and the role police will play in delineating between possession for personal use or trafficking purposes. Conclusions: The findings underscore the importance of monitoring the impact of the threshold on people who use drugs and whether it is countering the goals of the policy. Consultations with people who use drugs can help policymakers understand the challenges they may face when trying to abide by this threshold. [ABSTRACT FROM AUTHOR]

Background: Health Canada posts the outcomes of all New Drug Submissions. In some cases, companies have withdrawn submissions or submissions have been rejected by Health Canada for new active substances (NAS). This study explores the reasons for those decisions and compares them with decisions made by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Methods: This is a cross-sectional analysis. Submissions for NAS between December 2015 and December 2022 were identified along with the original indications for the NAS, the information that Health Canada had available and the reasons for its decisions. Similar information was sourced from the FDA and the EMA. Their decisions were compared to those made by Health Canada. The time between decisions by Health Canada, the FDA and the EMA were calculated in months. Results: Health Canada considered 272 NAS and approved 257. Sponsors withdrew 14 submissions for 13 NAS and Health Canada rejected submissions for 2 NAS. The FDA approved 7 of these NAS and the EMA approved 6, rejected 2 and submissions were withdrawn by 2 companies. Health Canada and the FDA considered similar information in 4 of 7 cases. Indications were the same except in one case. The FDA made decisions a mean of 15.5 months (interquartile range 11.4, 68.2) before companies withdrew their submissions from Health Canada. There were 5 cases where Health Canada and the EMA considered the same information and in 2 of those the outcome was different. Health Canada and EMA decisions were generally made within 1–2 months of each other. Indications were the same in all cases. Conclusions: Differences in decision making by regulators are due to more than the data which with they are presented, the timing of the presentations and the indications for the drugs. Regulatory culture may have influenced decision making. [ABSTRACT FROM AUTHOR]

Because we are not aware of any study that has scrutinized drugs not launched in Canada, we sought to take a first step in assessing these drugs and determining whether their limited access warrants concern. Only 2 of the PMPRB11 countries, Japan and Australia, are not represented in the EMA and, like Canada, have their own drug approval body. An assessment of drugs approved internationally between 2016 and 2020 and not submitted for Health Canada review Sources: Meds Entry Watch 2016, 2017, 2018, 5th and 6th editions;[6]-[10] Health Canada's Notice of Compliance database; Health Canada's New Drug Submissions Completed website; and Health Canada's New Drug Submissions Under Review website. [Extracted from the article]

Health Canada approved pembrolizumab in the first-line setting for advanced non-small-cell lung cancer with PD-L1 ≥ 50% and no EGFR/ALK aberration. The keynote 024 trial showed 55% of such patients progress with pembrolizumab monotherapy. We propose that the combination of baseline CT and clinical factors can help identify those patients who may progress. In 138 eligible patients from our institution, we retrospectively collected their baseline variables, including baseline CT findings (primary lung tumor size and metastatic site), smoking pack years, performance status, tumor pathology, and demographics. The treatment response was assessed via RECIST 1.1 using the baseline and first follow-up CT. Associations between the baseline variables and progressive disease (PD) were tested by logistic regression analyses. The results showed 46/138 patients had PD. The baseline CT "number of involved organs" by metastasis and smoking pack years were independently associated with PD (p < 0.05), and the ROC analysis showed a good performance of the model that integrated these variables in predicting PD (AUC: 0.79). This pilot study suggests that the combination of baseline CT disease and smoking PY can identify who may progress on pembrolizumab monotherapy and can potentially facilitate decision-making for the optimal first-line treatment in the high PD-L1 cohort. [ABSTRACT FROM AUTHOR]

A solid formulation of the pesticide TFM (4-nitro-3-(trifluoromethyl)-phenol) was developed in the 1980s for application in small tributaries during treatments to control invasive sea lamprey (Petromyzon marinus Linnaeus, 1758). Several initial inert ingredients were discontinued and substituted, culminating with an interim formulation that unacceptably softens and rapidly decays in warm conditions. A new TFM bar formulation was developed to resolve poor thermal stability and it was registered with the U.S. Environmental Protection Agency and Health Canada Pesticide Management Regulatory Agency in 2020. Laboratory studies compared the thermostability and dissolution (i.e., TFM release) of the interim and new formulation of TFM bars that were held at 20 °C or 45 °C for 24 hours prior to evaluation. Field tests compared the dissolution of the interim and new formulation of TFM bars when applied in three small tributaries in Michigan. Laboratory tests show that the new formulation bars remain usable when held at 45 °C for 24 hours; whereas, the interim formulation bars partially liquify and are not usable. Field tests indicate the new formulation bars have superior characteristics including a near consistent release of TFM for 10-13 hours when applied in waters with a velocity of < 0.06 m/sec. A near consistent release of TFM was observed for a maximum of about 6 hours in one field application of the interim formulation bars. Water temperature and water velocity influenced both formulations; however, the greatest effects were observed with interim formulation bars where higher initial TFM concentrations were followed by precipitous TFM concentration decreases in tributaries with the highest water temperature or velocity. Field treatment applications will provide data for refining application parameters such as the number of bars required per unit discharge at various water temperatures and the acceptable water velocity range for applications. [ABSTRACT FROM AUTHOR]

The Morone saxatilis (Striped Bass) population in Saint John River (SJR), NB, Canada, collapsed in the 1970s concurrent with dam construction, overfishing, and chemical pollution that may have impeded reproduction. To assess whether a chemical threat to Striped Bass or a health threat to fish consumers persists, we examined DDT and total mercury (THg) levels from 29 Striped Bass captured in the SJR including 16 genomically typed as SJR natives. DDT and DDD in female gonads were below detectable levels, and DDE averaged 0.08 ± 0.09 mg/kg wet weight (ww) but was considered too low to threaten reproduction. Total mercury in muscle and liver varied from 0.68 to 2.10 mg/kg and 0.35 to 3.27 mg/kg ww, respectively and exceeded Health Canada guidelines in all samples. We suggest regulators should update advisories for consumption including actively informing the public of the risk. [ABSTRACT FROM AUTHOR]

The multidrug-resistant (MDR) human immunodeficiency virus 1 (HIV-1) infection is an unmet medical need. HIV-1 capsid plays an important role at different stages of the HIV-1 replication cycle and is an attractive drug target for developing therapies against MDR HIV-1 infection. Lenacapavir (LEN) is the first-in-class HIV-1 capsid inhibitor approved by the USFDA, EMA, and Health Canada for treating MDR HIV-1 infection. This article highlights the development, pharmaceutical aspects, clinical studies, patent literature, and future directions on LEN-based therapies. The literature for this review was collected from PubMed, authentic websites (USFDA, EMA, Health Canada, Gilead, and NIH), and the free patent database (Espacenet, USPTO, and Patent scope). LEN has been developed by Gilead and is marketed as Sunlenca (tablet and subcutaneous injection). The long-acting and patient-compliant LEN demonstrated a low level of drug-related mutations, is active against MDR HIV-1 infection, and does not reveal cross-resistance to other anti-HIV drugs. LEN is also an excellent drug for patients having difficult or limited access to healthcare facilities. The literature has established additive/synergistic effects of combining LEN with rilpivirine, cabotegravir, islatravir, bictegravir, and tenofovir. HIV-1 infection may be accompanied by opportunistic infections such as tuberculosis (TB). The associated diseases make HIV treatment complex and warrant drug interaction studies (drug–drug, drug–food, and drug–disease interaction). Many inventions on different aspects of LEN have been claimed in patent literature. However, there is a great scope for developing more inventions related to the drug combination of LEN with anti-HIV/anti-TB drugs in a single dosage form, new formulations, and methods of treating HIV and TB co-infection. Additional research may provide more LEN-based treatments with favorable pharmacokinetic parameters for MDR HIV-1 infections and associated opportunistic infections such as TB. [ABSTRACT FROM AUTHOR]

The combination of mid-infrared and photoacoustic spectroscopy has shown promising developments as a substitute for invasive glucose detection technology. A dual single-wavelength quantum cascade laser system has been developed using photoacoustic spectroscopy for noninvasive glucose monitoring. Biomedical skin phantoms with similar properties to human skin have been prepared with blood components at different glucose concentrations as test models for the setup. The detection sensitivity of the system has been improved to ± 12.5 mg/dL in the hyperglycemia blood glucose ranges. An ensemble machine learning classifier has been developed to predict the glucose level in the presence of blood components. The model, which was trained with 72,360 unprocessed datasets, achieved a 96.7% prediction accuracy with 100% of the predicted data located in zones A and B of Clarke's error grid analysis. These findings fulfill both the US Food and Drug Administration and Health Canada requirements for glucose monitors. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases (CVDs) are the second leading cause of total deaths in Canada. High blood pressure is the main metabolic risk factor for developing CVDs. It has been well established that excess consumption of sodium adversely affects blood pressure. Canadians' mean sodium intakes are well above recommended levels. Reducing dietary sodium intake through food reformulation has been identified as a cost-effective intervention, however, dietary sodium intake and the potential health impact of meeting recommended sodium intake levels due to food reformulation have not been determined in Canada. Objective: This study aimed to 1) obtain robust estimates of Canadians' usual sodium intakes, 2) model sodium intakes had foods been reformulated to align with Health Canada's sodium reduction targets, and 3) estimate the number of CVD deaths that could be averted or delayed if Canadian adults were to reduce their mean sodium intake to recommended levels under three scenarios: A) 2,300 mg/d–driven by a reduction of sodium levels in packaged foods to meet Health Canada targets (reformulation); B) 2,000 mg/d to meet the World Health Organization (WHO) recommendation; and C) 1,500 mg/d to meet the Adequate Intake recommendation. Methods: Foods in the University of Toronto's Food Label Information Program 2017, a Canadian branded food composition database, were linked to nationally representative food intake data from the 2015 Canadian Community Health Survey–Nutrition to estimate sodium intakes (and intakes had Health Canada's reformulation strategy been fully implemented). The Preventable Risk Integrated ModEl (PRIME) was used to estimate potential health impact. Results: Overall, mean sodium intake was 2758 mg/day, varying by age and sex group. Based on 'reformulation' scenario A, mean sodium intakes were reduced by 459 mg/day, to 2299 mg/day. Reducing Canadians' sodium intake to recommended levels under scenarios A, B and C could have averted or delayed 2,176 (95% UI 869–3,687), 3,252 (95% UI 1,380–5,321), and 5,296 (95% UI 2,190–8,311) deaths due to CVDs, respectively, mainly from ischaemic heart disease, stroke, and hypertensive disease. This represents 3.7%, 5.6%, and 9.1%, respectively, of the total number of CVDs deaths observed in Canada in 2019. Conclusion: Results suggest that reducing sodium intake to recommended levels could prevent or postpone a substantial number of CVD deaths in Canada. Reduced sodium intakes could be achieved through reformulation of the Canadian food supply. However, it will require higher compliance from the food industry to achieve Health Canada's voluntary benchmark sodium reduction targets. [ABSTRACT FROM AUTHOR]

Background: Children are frequently exposed to marketing on food packaging. This study evaluated the presence, type and power of child-appealing marketing and compared the nutritional quality of child-appealing vs. non-child-appealing Canadian packaged foods and examined the relationship between nutrient composition and marketing power. Methods: Child-relevant packaged foods (n = 5,850) were sampled from the Food Label Information Program 2017 database. The presence and power (# of techniques displayed) of child-appealing marketing were identified. Fisher's Exact test compared the proportion of products exceeding Health Canada's nutrient thresholds for advertising restrictions and Mann Whitney U tests compared nutrient composition between products with child- /non-child-appealing packaging. Pearson's correlation analyzed the relationship between nutrient composition and marketing power. Results: 13% (746/5850) of products displayed child-appealing marketing; the techniques used, and the power of the marketing varied (x¯ 2.2 techniques; range: 0–11). More products with child-appealing packaging than with non-child appealing packaging exceeded Health Canada's thresholds (98% vs. 94%; p <.001). Products with child-appealing packaging (vs. non-child-appealing) were higher in total sugars (median: 14.7 vs. 9 g/RA; p <.001) and free sugars (11.5 vs. 6.2 g/RA; p <.001), but lower in all other nutrients. There was weak overall correlation between marketing power and nutrient levels. Results varied by nutrient and food category. Conclusions: Unhealthy products with powerful child-appealing marketing displayed on package are prevalent in the food supply. Implementing marketing restrictions that protect children should be a priority. [ABSTRACT FROM AUTHOR]

Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare, life-threatening, genetic condition characterized by markedly elevated levels of low-density lipoprotein cholesterol (LDL-C). Standard lipid-lowering therapies minimally reduce LDL-C in these patients, and lifelong serial apheresis is the mainstay of treatment. Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 that lowers LDL-C levels via a novel LDL receptor–independent mechanism, and is US Food and Drug Administration approved for HoFH in the United States. We present a pediatric HoFH patient from Ontario who has been receiving evinacumab through special access from Health Canada. A 17-year-old boy was diagnosed with severe HoFH due to compound heterozygous LDLR pathogenic variants. Treatment has included a statin, ezetimibe, and LDL apheresis every 2 weeks, with minimal overall effect on LDL-C levels. He remains asymptomatic from a cardiovascular perspective. At age 16, evinacumab infused intravenously every 4 weeks was added to his treatment. After 12 months, his time-averaged LDL-C decreased by 53.4% from 8.75 mmol/L (338.4 mg/dL) to 4.08 mmol/L (157.8 mg/dL), despite reduced frequency of LDL apheresis from biweekly to monthly. He has experienced no adverse events. Overall, treatment has increased quality of life for him and his family. Evinacumab shows great promise for patients with HoFH, a difficult-to-treat and potentially life-threatening condition. [ABSTRACT FROM AUTHOR]