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The rapid proliferation of businesses engaged in direct-to-consumer advertising of unproven stem cell interventions has raised troubling questions about whether government bodies can regulate this health market effectively. Recent developments in Australia and Canada suggest that such fears are unfounded and that targeted regulatory action can have meaningful effects., Competing Interests: Declaration of interests J.E.J.R. has advisory roles in the Gene Technology Technical Advisory Committee, Office of the Gene Technology Regulator, Australian Government; in the Human Research Ethics Committee, Genea; and as a member of the Data Safety Monitoring Board for a Fanconi anemia trial. He has shareholdings with Rarecyte and Woke and receives grant/research support from the NHMRC (GNT1177305), the NSWCC, the CINSW, the MRFF, Therapeutic Innovation Australia, and philanthropic foundations. J.E.J.R. receives supply of material (MTA), consultancy, or honoraria from Rarecyte; Novartis; bluebird bio; Spark Therapeutics, Inc.; Cynata Therapeutics; Pfizer; and CRISPRTx. He is a member of the board of directors or an advisory committee for these bodies: AAVec Bio, cofounder, and Kennerton Capital, non-executive director. He is employed by the Sydney Local Health District at Royal Prince Alfred Hospital. L.T. served as a compensated expert witness for the US government in a criminal case and as a pro bono expert witness in a class action lawsuit. He is a member of the International Society for Cell & Gene Therapy and its Ethics of Cell and Gene Therapy Committee. He is also a member of the International Society for Stem Cell Research and its Ethics Committee. L.T.’s research program has received funding from the Pew Charitable Trusts and the University of California, Irvine. L.I. served as a pro bono expert witness in a class action lawsuit. He is a member of the International Society for Cell & Gene Therapy and its Ethics of Cell and Gene Therapy Committee. He is also a member of the International Society for Stem Cell Research. L.I.’s research program has received funding from the US National Institutes of Health and the University at Buffalo. M.M. serves on the board of the International Society for Stem Cell Research and is a member of its Ethics and Public Policy Committees. She is the President of the Australasian Society for Stem Cell Research and a board member of the National Stem Cell Foundation of Australia. M.M.’s research program receives funding from reNEW, the Novo Nordisk Foundation Center for Stem Cell Medicine (NNF21CC0073729), and the Australian Government Medical Research Future Fund (APP2007623)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Generating rigorous evidence to inform care for rare diseases requires reliable, sustainable, and longitudinal measurement of priority outcomes. Having developed a core outcome set for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, we aimed to assess the feasibility of prospective measurement of these core outcomes during routine metabolic clinic visits., Methods: We used existing cohort data abstracted from charts of 124 children diagnosed with MCAD deficiency who participated in a Canadian study which collected data from birth to a maximum of 11 years of age to investigate the frequency of clinic visits and quality of metabolic chart data for selected outcomes. We recorded all opportunities to collect outcomes from the medical chart as a function of visit rate to the metabolic clinic, by treatment centre and by child age. We applied a data quality framework to evaluate data based on completeness, conformance, and plausibility for four core MCAD outcomes: emergency department use, fasting time, metabolic decompensation, and death., Results: The frequency of metabolic clinic visits decreased with increasing age, from a rate of 2.8 visits per child per year (95% confidence interval, 2.3-3.3) among infants 2 to 6 months, to 1.0 visit per child per year (95% confidence interval, 0.9-1.2) among those ≥ 5 years of age. Rates of emergency department visits followed anticipated trends by child age. Supplemental findings suggested that some emergency visits occur outside of the metabolic care treatment centre but are not captured. Recommended fasting times were updated relatively infrequently in patients' metabolic charts. Episodes of metabolic decompensation were identifiable but required an operational definition based on acute manifestations most commonly recorded in the metabolic chart. Deaths occurred rarely in these patients and quality of mortality data was not evaluated., Conclusions: Opportunities to record core outcomes at the metabolic clinic occur at least annually for children with MCAD deficiency. Methods to comprehensively capture emergency care received at outside institutions are needed. To reduce substantial heterogeneous recording of core outcome across treatment centres, improved documentation standards are required for recording of recommended fasting times and a consensus definition for metabolic decompensations needs to be developed and implemented., (© 2024. The Author(s).)

Background: Despite advances in defibrillation technology, shock-refractory ventricular fibrillation remains common during out-of-hospital cardiac arrest. Double sequential external defibrillation (DSED; rapid sequential shocks from two defibrillators) and vector-change (VC) defibrillation (switching defibrillation pads to an anterior-posterior position) have been proposed as defibrillation strategies to improve outcomes in patients with refractory ventricular fibrillation., Methods: We conducted a cluster-randomized trial with crossover among six Canadian paramedic services to evaluate DSED and VC defibrillation as compared with standard defibrillation in adult patients with refractory ventricular fibrillation during out-of-hospital cardiac arrest. Patients were treated with one of these three techniques according to the strategy that was randomly assigned to the paramedic service. The primary outcome was survival to hospital discharge. Secondary outcomes included termination of ventricular fibrillation, return of spontaneous circulation, and a good neurologic outcome, defined as a modified Rankin scale score of 2 or lower (indicating no symptoms to slight disability) at hospital discharge., Results: A total of 405 patients were enrolled before the data and safety monitoring board stopped the trial because of the coronavirus disease 2019 pandemic. A total of 136 patients (33.6%) were assigned to receive standard defibrillation, 144 (35.6%) to receive VC defibrillation, and 125 (30.9%) to receive DSED. Survival to hospital discharge was more common in the DSED group than in the standard group (30.4% vs. 13.3%; relative risk, 2.21; 95% confidence interval [CI], 1.33 to 3.67) and more common in the VC group than in the standard group (21.7% vs. 13.3%; relative risk, 1.71; 95% CI, 1.01 to 2.88). DSED but not VC defibrillation was associated with a higher percentage of patients having a good neurologic outcome than standard defibrillation (relative risk, 2.21 [95% CI, 1.26 to 3.88] and 1.48 [95% CI, 0.81 to 2.71], respectively)., Conclusions: Among patients with refractory ventricular fibrillation, survival to hospital discharge occurred more frequently among those who received DSED or VC defibrillation than among those who received standard defibrillation. (Funded by the Heart and Stroke Foundation of Canada; DOSE VF ClinicalTrials.gov number, NCT04080986.)., (Copyright © 2022 Massachusetts Medical Society.)

Introduction: End-tidal carbon dioxide (ETCO2) has been suggested to have prognostic implications during out-of-hospital cardiac arrest (OHCA). Our objective was to determine if the change in ETCO2 (delta ETCO2) during resuscitation was predictive of future return of spontaneous circulation (ROSC) in patients with pulseless electrical activity (PEA) arrests., Methods: We performed a retrospective, observational study of adult (≥18 years of age) non-traumatic PEA OHCAs in two Canadian EMS systems over a two-year time frame beginning on January 1, 2018. Cases were excluded if there was a Do Not Resuscitate order (DNR), had no advanced airway, or had less than two ETCO2 recordings. We performed multivariable logistic regression to examine the association between ETCO2 measures and ROSC. Second, we examined the prognostic performance (sensitivity, specificity, NPV, PPV) for ETCO2 at specific thresholds for predicting ROSC., Results: A total of 208 OHCA met inclusion criteria of which 67 (32%) obtained ROSC. After adjusting for pre-determined confounders, there was an association between delta ETCO2 and ROSC (odds ratio [OR] per 10 mmHg increase in ETCO2 of 1.74 (95% confidence interval [CI] 1.35 to 2.24); P value < 0.001). We also found significant associations between both initial ETCO2 and final ETCO2 with ROSC., Conclusion: Our analysis indicates that there is a positive linear relationship between delta ETCO2 and ROSC with values of delta ETCO2 > 20 mmHg being highly specific for ROSC in PEA patients. As such, patients with up-trending ETCO2 values should have resuscitation continued unless there is overwhelming clinical evidence to the contrary., Competing Interests: Declaration of Competing Interest Dr. Cheskes has received a speaking honorarium for educational events on CPR quality from Zoll Medical and Stryker Corporation. Dr. Cheskes has received grant funding from the Laerdal Foundation for the DOSE VF pilot RCT. Dr. Cheskes has received grant funding from HSF Canada for the DOSE VF RCT. Dr. Cheskes has received grant funding from Zoll Medical for AED on the Fly, Community Responder Program for Peel Region and Monitoring Ventilation during OHCA research studies. Dr. Cheskes sits on the Advisory Board of Drone Delivery Canada. No other authors have any conflicts of interest to declare., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: The primary objective was to determine the feasibility and safety of a cluster randomized controlled trial (RCT) with crossover comparing vector change defibrillation (VC) or double sequential external defibrillation (DSED) to standard defibrillation for patients experiencing refractory ventricular fibrillation (VF). Secondary objectives were to assess the rates of VF termination (VFT) and return of spontaneous circulation (ROSC)., Methods: We conducted a pilot cluster RCT with crossover in four Canadian paramedic services including all treated adult OHCA patients who presented in VF and received a minimum of three successive defibrillation attempts. Each EMS service was randomly assigned to provide standard defibrillation, VC or DSED. Agencies crossed over to an alternate defibrillation strategy after six months., Results: 152 patients were enrolled. With respect to feasibility, 89.5% of cases received the defibrillation strategy they were randomly allocated to, and 93.1% of cases received a VC or DSED shock prior to the sixth defibrillation attempt. There were no safety concerns reported. In the standard group, 66.6% of cases resulted in VFT, compared to 82.0% in VC and 76.3% in the DSED group. ROSC was achieved in 25.0%, 39.3% and 40.0% of standard, VC and DSED groups, respectively., Conclusions: Our findings suggest the DOSE-VF protocol is feasible and safe. Rates of VFT and ROSC were higher in the VC and DSED than standard defibrillation. The results of this pilot trial will allow us to inform a multicenter cluster RCT with crossover to determine if alternate defibrillation strategies for refractory VF may impact clinical outcomes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The Canadian Inherited Metabolic Diseases Research Network (CIMDRN) is a pan-Canadian practice-based research network of 14 Hereditary Metabolic Disease Treatment Centres and over 50 investigators. CIMDRN aims to develop evidence to improve health outcomes for children with inherited metabolic diseases (IMD). We describe the development of our clinical data collection platform, discuss our data quality management plan, and present the findings to date from our data quality assessment, highlighting key lessons that can serve as a resource for future clinical research initiatives relating to rare diseases., Methods: At participating centres, children born from 2006 to 2015 who were diagnosed with one of 31 targeted IMD were eligible to participate in CIMDRN's clinical research stream. For all participants, we collected a minimum data set that includes information about demographics and diagnosis. For children with five prioritized IMD, we collected longitudinal data including interventions, clinical outcomes, and indicators of disease management. The data quality management plan included: design of user-friendly and intuitive clinical data collection forms; validation measures at point of data entry, designed to minimize data entry errors; regular communications with each CIMDRN site; and routine review of aggregate data., Results: As of June 2019, CIMDRN has enrolled 798 participants of whom 764 (96%) have complete minimum data set information. Results from our data quality assessment revealed that potential data quality issues were related to interpretation of definitions of some variables, participants who transferred care across institutions, and the organization of information within the patient charts (e.g., neuropsychological test results). Little information was missing regarding disease ascertainment and diagnosis (e.g., ascertainment method - 0% missing)., Discussion: Using several data quality management strategies, we have established a comprehensive clinical database that provides information about care and outcomes for Canadian children affected by IMD. We describe quality issues and lessons for consideration in future clinical research initiatives for rare diseases, including accurately accommodating different clinic workflows and balancing comprehensiveness of data collection with available resources. Integrating data collection within clinical care, leveraging electronic medical records, and implementing core outcome sets will be essential for achieving sustainability.

Objective: Limited evidence supports primary care paramedic (PCP) direct transport of ST-segment elevation myocardial infarction (STEMI) patients for percutaneous coronary intervention (PCI). The goal of this study was to evaluate an urban-based PCP STEMI bypass guideline., Methods: We reviewed consecutive Toronto Paramedic Services call reports between April 7, 2015, and May 31, 2016, regarding STEMI patients identified by PCPs. The primary outcome was patient assignment (stable versus unstable) according to guideline criteria. Secondary outcomes were the proportion of PCP-transported patients who had an indication for an advanced care intervention (ACI) or who received an ACI when PCPs rendezvoused with an advanced care paramedic (ACP). Lastly, we reviewed prehospital outcomes of cardiac arrest patients and calculated the difference in transport intervals between direct PCP bypass and a PCI-centre and predicted transport interval to the closest emergency department (ED)., Results: Of 361 patients, 232 were PCP transports and 129 were ACP-rendezvous transports. There was a significant difference in the distribution of stable and unstable patients between PCPs and ACPs (p<0.001). For PCP patients, 21/232 (9.1%) had indications for an ACI, whereas 34/129 (26.4%) ACP patients received an ACI. Eleven patients experienced cardiac arrest; 10 were successfully resuscitated (5 of these by PCPs). The median difference between direct PCP bypass and a PCI-centre versus transport to the closest ED was 5.53 minutes (IQR=6.71)., Conclusions: We found a significant difference in the distribution of stable and unstable patients and fewer patients with indications for an ACI in PCP patients. This PCP STEMI bypass guideline appears feasible.

Aim: This study examines marketing claims of Canadian businesses engaged in direct-to-consumer advertising of putative stem cell treatments., Methods: Internet searches were used to locate Canadian businesses selling stem cell interventions. Company websites were subjected to detailed analysis., Results: In total, 30 Canadian businesses sell stem cell interventions provided at 43 clinics. Autologous stem cells are the most common types of products promoted by such businesses. Company websites minimize risks while making strong claims about benefits of stem cell interventions., Discussion: Businesses' representations could result in patients making health-related decisions informed by marketing claims rather than best available scientific evidence., Conclusion: Although there is absent development of new regulations and guidance, the Canadian direct-to-consumer marketplace for stem cell interventions appears poised for expansion.

Background/aim: Youth with physical disabilities experience restrictions to participation in community-based leisure activities; however, there is little evidence about how to improve their involvement. This study examined whether an intervention to remove environmental barriers and develop strategies using a coaching approach improved youth participation in leisure activities., Methods: An Interrupted Time Series design was employed, where replication of the intervention effect was examined across individualised participation goals and across participants. Six adolescents with a physical disability participated in a 12-week intervention. An occupational therapist worked with each youth and his/her family to set three leisure goals based on problems identified using the Canadian Occupational Performance Measure (COPM). A coaching approach was used to collaboratively identify and implement strategies to remove environmental barriers. Interventions for each goal were introduced at different time points. Outcomes were evaluated using the COPM., Results: Improvements in COPM performance scores were clinically significant for 83% of the identified activities; an average change of 4.5 points in the performance scale (SD = 1.95) was observed. Statistical analysis using the celeration line demonstrated that the proportion of data points falling above the line increased in the intervention phase for 94% of the activities, indicating a significant treatment effect., Conclusions: This study is the first to examine an intervention aimed at increasing leisure participation by changing only the environment. The results indicate that environment-focussed interventions are feasible and effective in promoting youth participation. Such findings can inform the design of a larger study and guide occupational therapy practice., (© 2015 Occupational Therapy Australia.)

Background: Despite having access to medically necessary care available through publicly funded provincial health care systems, some Canadians travel for treatment provided at international medical facilities as well as for-profit clinics found in several Canadian provinces. Canadians travel abroad for orthopaedic surgery, bariatric surgery, ophthalmologic surgery, stem cell injections, "Liberation therapy" for multiple sclerosis, and additional interventions. Both responding to public interest in medical travel and playing an important part in promoting the notion of a global marketplace for health services, many Canadian companies market medical travel., Methods: Research began with the goal of locating all medical tourism companies based in Canada. Various strategies were used to find such businesses. During the search process it became apparent that many Canadian business promoting medical travel are not medical tourism companies. To the contrary, numerous types of businesses promote medical travel. Once businesses promoting medical travel were identified, content analysis was used to extract information from company websites. Company websites were analyzed to establish: 1) where in Canada these businesses are located; 2) the destination countries and health care facilities that they market; 3) the medical procedures they promote; 4) core marketing messages; and 5) whether businesses market air travel, hotel accommodations, and holiday tours in addition to medical procedures., Results: Searches conducted from 2006 to 2011 resulted in identification of thirty-five Canadian businesses currently marketing various kinds of medical travel. The research project began with what seemed to be the straightforward goal of establishing how many medical tourism companies are based in Canada. Refinement of categories resulted in the identification of eighteen businesses fitting the category of what most researchers would identify as medical tourism companies. Seven other businesses market regional, cross-border health services available in the United States and intranational travel to clinics in Canada. In contrast to medical tourism companies, they do not market holiday tours in addition to medical care. Two companies occupy a narrow market niche and promote testing for CCSVI and "Liberation therapy" for multiple sclerosis. Three additional companies offer bariatric surgery and cosmetic surgery at facilities in Mexico. Four businesses offer health insurance products intended to cover the cost of obtaining privately financed health care in the U.S. These businesses also help their clients arrange treatment beyond Canada's borders. Finally, one medical travel company based in Canada markets health services primarily to U.S. citizens., Conclusions: This article uses content analysis of websites of Canadian companies marketing medical travel to provide insight into Canada's medical travel industry. The article reveals a complex marketplace with different types of companies taking distinct approaches to marketing medical travel.

When Canadian researchers examine the subject of medical tourism, they typically focus on ethical, social, public health and health policy issues related to Canadians seeking health services in other countries. They emphasize study of Canada as a departure point for medical tourists rather than as a potential destination for international patients. Several influential voices have recently argued that provincial healthcare systems in Canada should market health services to international patients. Proponents of marketing Canada as a destination for medical tourists argue that attracting international patients will generate revenue for provincial healthcare systems. Responding to such proposals, I argue that there are at least seven reasons why provincial health systems in Canada should not dedicate institutional, financial and health human resources to promoting themselves as destinations for medical tourists.

The practice of medical tourism depends on successfully informing potential patients about procedure options, treatment facilities, tourism opportunities, travel arrangements, and destination countries. The promotion of medical tourism includes a wide range of marketing materials such as flyers, booklets, and websites. Yet, there is a paucity of knowledge about the dissemination, content, and reception of these promotional materials. Drawing on a thematic content analysis of the promotional print material distributed at the first medical tourism trade show in Canada in 2009, the main purpose of this article is to identify and understand the messages and images that companies use to market India as a global destination. While researchers and news media frequently cite low cost procedures as a key determinant for international patient travel, particularly to developing nations, our analysis reveals few low cost-related images or messages in the promotional materials distributed at the trade show. To help explain this surprising disjuncture, we consider four related issues: (1) promotional materials may be designed to be circulated amongst potential patients' concerned family and friends who privilege knowing about things such as the use of advanced technologies; (2) developing nations need to portray safe and advanced treatment facilities in order to dispel potential patients' suspicions that their medical care is inferior; (3) companies may avoid making cost saving claims that cannot be fulfilled for all of their international patients, especially those traveling from developing nations; and (4) messages of low cost may detract from and even undermine messages about quality. We conclude by identifying numerous avenues for future research by social and health scientists, and by considering the implications of our findings for existing knowledge gaps and debates within health geography specifically., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Health-related travel, also referred to as "medical tourism" is historically well-known. Its emerging contemporary form suggests the development of a form of globalised for-profit healthcare. Medical tourism to India, the focus of a recent conference in Canada, provides an example of the globalisation of healthcare. By positioning itself as a low-cost, high-tech, fast-access and high-quality healthcare destination country, India offers healthcare to medical travellers who are frustrated with waiting lists and the limited availability of some procedures in Canada. Although patients have the right to travel and seek care at international medical facilities, there are a number of dimensions of medical tourism that are disturbing. The diversion of public investments in healthcare to the private sector, in order to serve medical travellers, perversely transfers public resources to international patients at a time when the Indian public healthcare system fails to provide primary healthcare to its own citizens. Further, little is known about patient safety and quality care in transnational medical travel. Countries that are departure points as well as destination countries need to carefully explore the ethical, social, cultural, and economic consequences of the growing phenomenon of for-profit international medical travel.

Chloroform has been assessed as a Priority Substance under the Canadian Environmental Protection Act. The general population in Canada is exposed to chloroform principally through inhalation of indoor air, particularly during showering, and through ingestion of tap water. Data on concentrations of chloroform in various media were sufficient to serve as the basis for development of deterministic and probabilistic estimates of exposure for the general population in Canada. On the basis of data acquired principally in studies in experimental animals, chloroform causes hepatic and renal tumors in mice and renal tumors in rats. The weight of evidence indicates that chloroform is likely carcinogenic only at concentrations that induce the obligatory precursor lesions of cytotoxicity and proliferative regenerative response. Since this cytotoxicity is primarily related to rates of formation of reactive, oxidative metabolites, dose response has been characterized in the context of rates of formation of reactive metabolites in the target tissue. Results presented here are from a "hybrid" physiologically based pharmacokinetic (PBPK) animal model that was revised to permit its extension to humans. The relevant measure of exposure response, namely, the mean rate of metabolism in humans associated with a 5% increase in tumor risk (TC05), was estimated on the basis of this PBPK model and compared with tissue dose measures resulting from 24-h multimedia exposure scenarios for Canadians based on midpoint and 95th percentiles for concentrations in outdoor air, indoor air, air in the shower compartment, air in the bathroom after showering, tap water, and food. Nonneoplastic effects observed most consistently at lowest concentrations or doses following repeated exposures of rats and mice to chloroform are cytotoxicity and regenerative proliferation. As for cancer, target organs are the liver and kidney. In addition, chloroform has induced nasal lesions in rats and mice exposed by both inhalation and ingestion at lowest concentrations or doses. The mean rate of metabolism associated with a 5% increase in fatty cysts estimated on the basis of the PBPK model was compared with tissue dose measures resulting from the scenarios already described, and lowest concentrations reported to induce cellular proliferation in the nasal cavities of rats and mice were compared directly with midpoint and 95th percentile estimates of concentrations of chloroform in indoor air in Canada. The degree of confidence in the underlying database and uncertainties in estimates of exposure and in characterization of hazard and dose response are delineated.