Proceedings of the immune thrombocytopenia summit: new concepts in mechanisms, diagnosis, and management.

The inaugural McMaster Immune Thrombocytopenia (ITP) Summit was held virually in 2021. The objectives of the Summit were to recognize the difficulties in establishing the diagnosis of ITP and to understand gaps in current knowledge of ITP mechanisms that might lead to better diagnostic approaches and treatments. The half-day program consisted of virtual educational sessions targeting clinicians and basic scientists. The planning committee chose 8 topics to review that would cover current knowledge and inform future research priorities. In this report, we summarized the presentations delivered at the 2021 McMaster ITP Summit and the discussions. Based on the information presented at the Summit, the following research priorities were identified: 1) investigation of platelet production as a target for ITP treatments; 2) characterization of antigen processing and antigen presentation on platelets; 3) interaction between megakaryocytes and the immune system; 4) the role for ITP gene panels; 5) the need for better methods for platelet antibody testing; 6) the role of prediction models for diagnosis and prognosis; 7) new treatment strategies, including intensification of initial therapy; and 8) personalized treatment algorithms.

Unique features of vaccine-induced immune thrombotic thrombocytopenia; a new anti-platelet factor 4 antibody-mediated disorder.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a highly prothrombotic disorder caused by anti-PF4 antibodies that activate platelets and neutrophils, leading to thrombosis. Heparin-induced thrombocytopenia (HIT) is a related anti-PF4 mediated disorder, with similar pathophysiology and clinical manifestations but different triggers (i.e., heparin vs adenoviral vector vaccine). Clinically, both HIT and VITT typically present with thrombocytopenia and thrombosis, although the risk of thrombosis is significantly higher in VITT, and the thromboses occur in unusual anatomical sites (e.g., cerebral venous sinus thrombosis and hepatic vein thrombosis). The diagnostic accuracy of available laboratory testing differs between HIT and VITT; for VITT, ELISAs have better specificity compared to HIT and platelet activation assays require the addition of PF4. Treatment of VITT and HIT is anticoagulation non-heparin anticoagulants; however, heparin may be considered for VITT if no other option is available.

Development and internal validation of a clinical prediction model for the diagnosis of immune thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (ITP) is a diagnosis of exclusion that can resemble other thrombocytopenic disorders. OBJECTIVES: To develop a clinical prediction model (CPM) for the diagnosis of ITP to aid hematogists in investigating patients presenting with undifferentiated thrombocytopenia. METHODS: We designed a CPM for ITP diagnosis at the time of the initial hematology consultation using penalized logistic regression based on data from patients with thrombocytopenia enrolled in the McMaster ITP registry (n = 523) called the Predict-ITP Tool. The case definition for ITP was a platelet count less than 100 × 109 /L and a platelet count response after high-dose corticosteroids or intravenous immune globulin, defined as the achievement of a platelet count above 50 × 109 /L and at least a doubling of baseline. Internal validation was done using bootstrap resampling. Model discrimination was assessed by the c-statistic, and calibration was assessed by the calibration slope, calibration-in-the-large, and calibration plot. RESULTS: The final model included the following variables: (1) platelet count variability (based on three or more platelet count values), (2) lowest platelet count value, (3) maximum mean platelet volume, and (4) history of major bleeding (defined by the ITP bleeding scale). The optimism-corrected c-statistic was 0.83, the calibration slope was 0.88, and calibration-in-the-large for all performance measures was <0.001 with standard error <0.001, indicating good discrimination and excellent calibration. CONCLUSIONS: The Predict-ITP Tool can estimate the likelihood of ITP for a given patient with thrombocytopenia at the time of the initial hematology consultation. The tool had high predictive accuracy for the diagnosis of ITP.

Nicotine content, labelling and flavours of e-liquids in Canada in 2020: a scan of the online retail market. / Teneur en nicotine, étiquetage et arômes des liquides à vapoter au Canada en 2020 : un survol du marché de la vente au détail en ligne.

INTRODUCTION: The e-cigarette market in Canada has rapidly evolved following the implementation of the Tobacco and Vaping Products Act in May 2018, which liberalized the promotion and sale of vaping products. To date, there is little data on the market profile of key product attributes, including nicotine content, labelling practices and flavours. METHODS: An online scan of vaping product retailers (manufacturer, two national, five provincial) was conducted in 2020 to assess the e-liquids available on the Canadian market. Data were extracted from websites and product images regarding the nicotine content, labelling and flavours of e-liquids. RESULTS: We identified 1746 e-liquids, with a total of 4790 different nicotine concentrations. Approximately half of the e-liquids were offered with salt-base nicotine (46.6%) and half with freebase nicotine (53.2%); the remainder were hybrids (0.2%). The mean nicotine concentration of salt-base e-liquids (3.4%) was higher than freebase e-liquids (0.5%) (p < 0.001). Labels indicating the presence of nicotine were visible on twothirds of e-liquid packaging displayed online (63.2%) while three-quarters of packaging displayed the nicotine concentration (73.7%), and more than half of packaging displayed health warnings (58.9%). A variety of flavours were also identified, with fruit being the most common (43.6%), followed by candy/desserts (27.6%) and non-alcoholic drinks (12.5%). CONCLUSION: Findings demonstrate the diversity of the online e-cigarette market in Canada, including the availability of higher-concentration salt-base nicotine products. Flavour restrictions have the potential to dramatically reduce the number of e-liquid flavours on the market, while restricting nicotine concentrations to < 20 mg/mL will predominantly restrict salt-based e-liquids.

Availability, retail price and potency of legal and illegal cannabis in Canada after recreational cannabis legalisation.

INTRODUCTION AND AIMS: There is little objective market data on the price or potency of legal and illegal cannabis products following recreational cannabis legalisation. DESIGN AND METHODS: In the 2 months post-legalisation in Canada (November-December 2018), legal and illegal cannabis retailers were identified from government lists and online directories. The store location, price and Δ9-tetrahydrocannabinol (THC) and cannabidiol levels of dried herb and cannabis cookies were collected from retailer websites or Weedmaps. RESULTS: We identified 185 legal retailers (22 online stores, 163 storefronts; 65 government-run stores, 120 private stores) and 944 illegal retailers (791 delivery-only services, 157 storefronts). Relative to legal dried herb, illegal dried herb was lower in price (1 g: $10.23 vs. $11.08, ⅛ oz: $9.37/g vs. $10.88/g, ½ oz: $8.18/g vs. $8.85/g; P < 0.05 for all) and higher in potency (THC: 20.5% vs. 16.1%, cannabidiol: 2.4% vs. 1.7%; P < 0.05 for both). Legal private stores had higher prices for dried herb than government-run stores (1 g: $13.08 vs. $10.89, ⅛ oz: $12.75/g vs. $10.45/g, ½ oz: $10.85/g vs. $8.71/g, 1 oz: $8.54/g vs. $7.22/g; P < 0.05 for all). On average, one cannabis cookie in the illegal market contained 96 mg of THC and cost $1.57 per 10 mg of THC. DISCUSSION AND CONCLUSIONS: In the 2 months post-legalisation, illegal cannabis was less expensive, with higher labelled THC content than legal cannabis, although the scope of these differences was more modest than estimates from other crowdsourced and self-reported data. Direct monitoring of cannabis price and potency from legal and illegal retailers is needed to examine the impact of legalisation over time.

Retail price and availability of illicit cannabis in Canada.

INTRODUCTION: This study sought to estimate the number of illicit retailers and the average price of cannabis in the largest municipality in each province and territory in Canada by obtaining information from retailers. METHODS: Online search engines were used to identify retailers in each municipality. The advertised prices for various volumes of the least expensive, most expensive, and most popular dry herb were determined using the retailer's website, Weedmaps, or Leafly. Data was collected between October 2017 and May 2018, including two waves in Toronto to examine changes over a five-month period. RESULTS: Across the 13 municipalities, 997 cannabis retailers were identified, including 215 physical storefronts. The average price per gram of cannabis was $10.02, $7.80, and $12.30 for the most popular, least expensive, and most expensive strains, respectively. The price-per-gram decreased as purchase volume increased: purchasing one-eighth of an ounce and one ounce of cannabis led to savings of up to 9% and 27%, respectively. Prices were consistent across municipalities, although the number of outlets varied greatly. Prices were similar between storefronts and delivery-only services; however, delivery services offered larger discounts for cannabis purchased by the ounce. The five-month comparison in Toronto revealed modest changes in the number of retailers and more pronounced changes in the price of the most popular and least expensive strains. CONCLUSION: The findings depict a well-established retail cannabis market in Canada in the year prior to legalization. The average advertised price of the most popular cannabis varieties was approximately $10, which aligns with the projected retail price of cannabis from licensed sources following legalization in Canada.

Exploring the effect of factor Xa inhibitors on rotational thromboelastometry: a case series of bleeding patients.

Direct oral anticoagulants (DOACs) have become the standard for thromboembolic risk management. In cases of major bleeding, trauma, or urgent surgery, accurate monitoring of DOAC activity is desirable; however, there is often no rapid, readily available test. We therefore explored the degree to which DOAC activity correlated with two coagulation assays: rotational thromboelastometry (ROTEM) and a standard coagulation assay in bleeding patients. We conducted a retrospective review of patients who experienced bleeding while on DOAC therapy from 2015 to 2017 at a Level 1 trauma center. ROTEM (EXTEM-clotting time {CT} in seconds), activated partial thromboplastin time (aPTT) (in seconds), prothrombin time (PT) (in seconds), DOAC specific drug test (anti-Xa and Hemoclot in ng/mL), and relevant clinical parameters were recorded. Descriptive statistics (median, range) and Spearman correlation coefficients were estimated. Differences between correlations were tested using Williams' t test. Twelve cases were reviewed (13 separate bleeding episodes). Sixteen measurements of DOAC activity, EXTEM-CT, and PT were obtained. The correlations with rivaroxaban activity were 0.96 and 0.86 (p = 0.2062) for PT and EXTEM-CT, respectively. The correlations with apixaban activity were 0.63 and 0.56 (p = 0.7175) for PT and EXTEM-CT, respectively. Analyses were not conducted for dabigatran due to limited data. Although not statistically significant, PT appears to have a higher correlation with direct Xa inhibitor activity than EXTEM-CT. Further research with larger samples is necessary to clarify the differences between ROTEM and standard assays in detecting DOAC activity.

The Impact of Front-of-Package Label Design on Consumer Understanding of Nutrient Amounts.

A between-groups experiment examined the salience of front-of-package (FOP) symbols. Adults from Canada, the US, Australia, and the UK completed an online survey (n = 11,617). Respondents were randomized to view cereal boxes displaying one of 11 FOP label conditions for 'high' levels of sugar and saturated fat: control (no FOP symbol), red circle, red 'stop sign', magnifying glass, magnifying glass + exclamation mark, and 'caution' triangle + exclamation mark, plus each of these five conditions accompanied by a 'high in' text descriptor. Participants identified the amount of saturated fat and sugar in the product ('low'/'moderate'/'high'). Participants were more likely to correctly identify the product as 'high' in saturated fat or sugar when shown the stop sign, triangle + exclamation mark, red circle, or magnifying glass + exclamation mark symbols incorporating 'high in' text (p < 0.01). The magnifying glass was the least effective symbol. The stop sign (37.7%) and triangle + exclamation mark (22.0%) were most frequently selected as the best symbol for indicating high nutrient amounts. Overall, FOP labels with 'high in' descriptions, red color and intuitive 'warning' symbols (e.g., stop signs, exclamation marks, 'caution' triangles) were more effective at communicating high levels of nutrients of public health concern in a time-limited environment.