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1.
PLoS One ; 19(5): e0299085, 2024.
Article in English | MEDLINE | ID: mdl-38718060

ABSTRACT

INTRODUCTION: Substance use is common among youth which can adversely affect youth health. Despite the legalization of cannabis in Canada and much of the United States, there is a lack of harm reduction cannabis education in schools. In addition, educators may not feel prepared to teach students about cannabis. METHODS: A cross-sectional survey explored educator perceptions toward teaching harm reduction substance use education to students in grades 4-12. Data analysis included descriptive statistics to evaluate demographic variables, ANOVAs to identify subgroup differences, and inductive thematic analysis to establish themes from open-ended responses. From the sample of 170 educators, the majority were female (77%) and worked as classroom teachers (59%). RESULTS: Ninety-two percent of educators felt harm reduction was an effective approach to substance use education, and 84% stated that they would feel comfortable teaching cannabis harm reduction education to students. While 68% of educators believed they would be able to recognize if a student was under the influence of cannabis, only 39% felt certain about how to respond to student cannabis use, and just 8% felt that their current teacher training allowed them to intervene and prevent cannabis-related harms. Most educators (89%) expressed interest in harm reduction training, particularly interactive training (70%) and instructor-led lessons (51%). Online curriculum resources were preferred by 57%. Responses differed by gender and age group, with females of any age and educators under 40 reporting greater support of harm reduction approaches and more interest in training. CONCLUSION: Educators expressed considerable support for harm reduction substance use education, but many felt unprepared to address this topic with students. The findings identified a need for educator training on harm reduction substance use education, so that educators can help students make informed choices around substance use, thereby promoting youth health and safety.


Subject(s)
Harm Reduction , Humans , Female , Male , Cross-Sectional Studies , Surveys and Questionnaires , Adult , Cannabis , Adolescent , Middle Aged , Students/psychology , Young Adult , Health Education/methods , Curriculum , Canada
2.
J Cannabis Res ; 6(1): 4, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38331901

ABSTRACT

BACKGROUND: With the legalization of cannabis in Canada, consumers are presented with numerous purchase options. Licensed retailers are limited by the Cannabis Act and provincial regulations with respect to offering sales, advertising, location, maximum quantities, and information sharing in an effort to protect public health and safety. The degree these policies influence consumer purchase behavior will help inform regulatory refinement. METHODS: A discrete choice experiment within a cross-sectional online survey was used to explore trade-offs consumers make when deciding where to purchase cannabis. Attributes included availability of sales/discounts, proximity, product information, customer service, product variety, and provincial regulation. Participants ≥ 19 years old who lived in Canada and purchased cannabis in the previous 12 months were recruited through an online market research survey panel. A multinomial logit (MNL) model was used for the base model, and latent class analysis was used to assess preference sub-groups. Key limitations included ordering effect, hypothetical bias, and framing effect. RESULTS: The survey was completed by 1626 people, and the base model showed that customer service carried the most weight in purchase decisions, followed by proximity and availability of sales and discounts. There was considerable heterogeneity in preference patterns, with a five-group latent class model demonstrating best fit. Only one group (15% of sample) placed a high value on the store being provincially regulated, while three groups were willing to make a trade-off with regulation to access better customer service, product information, or closer proximity. One group preferred non-regulated sources (24% of sample); this group was also primarily driven by the availability of sales and discounts. Three groups (60.5% of sample) preferred online stores. CONCLUSION: This study highlighted that there exists significant diversity with respect to the influence of consumer experiences on cannabis purchase behaviors. Modifications to cannabis retail regulations that focus on improving access to product information as well as reviewing limitations on sales and discounts could have the most impact for shifting customers to licensed retailers.

3.
Health Educ J ; 82(7): 766-778, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37927456

ABSTRACT

Background: The 2018 legalisation of cannabis in Canada sparked concern and conversation about the potential negative impacts of youth cannabis use. It is clear that young people are already engaging in cannabis use for a variety of reasons; therefore, youth cannabis education is desirable to promote harm reduction and reduce the risk of adverse physical and mental health outcomes. Objective: To identify and categorise Canadian cannabis education resources using a social-ecological approach informed by the youth health literacy framework, considering multiple factors at the micro-, meso- and macro-levels that influence health literacy and impact behaviour. Methods: In line with scoping review methodology, database searches and an environmental scan of materials were completed. Specific inclusion criteria were identified to encompass all Canadian cannabis education resources directed towards young people aged 9-18 years and adults in contact with youth. Results: A total of 60 resources were identified and categorised using the youth health literacy framework in terms of their focus on (1) micro influences (resources for youth); (2) meso influences (resources for teachers, parents, mentors); and (3) macro influences (resources for indigenous communities and medical professionals). Conclusions: While many resources were identified, issues exist with the accessibility, quality and multicultural considerations of such resources, warranting the development of comprehensive, evidence-based and harm reduction-focused cannabis education for youth.

4.
Int J Drug Policy ; 120: 104193, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37716112

ABSTRACT

BACKGROUND: Emerging adults (EAs) have the highest rates of cannabis consumption in Canada and are vulnerable to the potential impacts of frequent cannabis consumption. This study assessed EAs' perceived risk of cannabis consumption across multiple domains of potential harm based on the age (14-year-old, 21-year-old, or 28-year-old) and sex (male or female) of the vignette character, time-point (pre- or post-legalization), and participant's gender. METHODS: Secondary analyses were conducted on data from a pre-legalization study and post-legalization replication. Participants included EAs between 18 and 25 years of age and living in Newfoundland and Labrador. Participants from the pre- and post-legalization studies were matched based on demographic variables and the assigned vignette character. Participants responded to seven items of perceived risk based on their assigned vignette character's (varied by age or sex) almost daily cannabis consumption. RESULTS: Participants (N = 689) viewed cannabis consumption to have greater risks for a 14-year-old compared to a 21- or 28-year-old in all domains except for social life. Prior to legalization, participants who identified as a woman felt that cannabis had more detrimental impacts on social life than participants who identified as a man. Findings also suggested that pre-legalization cannabis consumption by a female was perceived as more detrimental to their social life than pre-legalization consumption by a male and post-legalization consumption by a female. CONCLUSION: EAs do not fully appreciate the risks of cannabis consumption, suggesting that it is imperative for public health strategies to promote increased awareness of the risks of frequent cannabis consumption, and improve cannabis health literacy in this population.

5.
J Stud Alcohol Drugs ; 84(5): 744-753, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37219026

ABSTRACT

OBJECTIVE: Cannabis was legalized for nonmedical use in Canada in 2018. However, with a long-established illegal market, it is important to understand cannabis consumers' preferences in order to create a market that encourages purchasing cannabis through legalized channels. METHOD: A survey including a discrete choice experiment was conducted to estimate preference weights for seven attributes of dried flower cannabis purchases (price, packaging, moisture level, potency, product recommendations, package information, and regulation by Health Canada). Participants were at least 19 years of age, lived in Canada, and purchased cannabis in the last 12 months. A multinomial logit (MNL) model was used for the base model, and latent class analyses to identify subgroups preference profiles. RESULTS: A total of 891 participants completed the survey. The MNL model showed that all attributes significantly influenced choice, except product recommendations. Potency and package information were most important. A three-group latent class model showed that about 30% of the sample were most concerned with potency, whereas two groups--jointly making up the remaining 70%--were most concerned with package type (about 40% preferred bulk packaging, and about 30% preferred pre-rolled joints). CONCLUSIONS: Consumer purchase preferences for dried flower cannabis were influenced by different attributes. Preference patterns can be grouped into three categories. About 30% of the population appeared to have their preferences met by the legalized market, whereas another 30% appeared to be more loyal to the unlicensed market. The remaining 40% represented a group that may be influenced through regulatory changes to simplify packaging and increase availability of product information.

6.
Appl Health Econ Health Policy ; 21(4): 651-659, 2023 07.
Article in English | MEDLINE | ID: mdl-37060511

ABSTRACT

BACKGROUND: Phase two of cannabis legalisation in Canada brought cannabis vaping products to the market. This decision was controversial due to an outbreak of vaping cannabis use-associated lung injury. This resulted in three provinces banning the sale of cannabis vaping products causing inequitable access. This study sought to explore consumer preferences for cannabis vaping products to inform cannabis policy. METHODS: We used a discrete choice experiment to explore consumer preferences for attributes of cannabis vaping products. Attributes included type of device, price, tetrahydrocannabinol (THC) potency, vape liquid content, product recommendations and Health Canada regulation. Participants lived in Canada, were aged ≥ 19 years, and had purchased a cannabis vape 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. RESULTS: In total, 384 participants completed the survey; the MNL model showed that price and potency were the most important attributes. A three-group latent class model showed that ~ 40% of the sample was driven primarily by Health Canada Regulation and were willing to pay $56 more for a product that was regulated compared to one that was not. About 33% of the sample was driven by price, and 26% was driven by type of device. CONCLUSION: While regulated status by Health Canada was most important to some consumers (~ 40%), nearly 60% of the sample were willing to make trade-offs in regulated status for products with a lower price. Therefore, policymakers need to consider the broader public health implications of banning cannabis vapes in some regions.


Subject(s)
Cannabis , Vaping , Humans , Consumer Behavior , Dronabinol , Health Policy
7.
J Adolesc Health ; 72(3): 404-411, 2023 03.
Article in English | MEDLINE | ID: mdl-36476394

ABSTRACT

PURPOSE: Increased access to legalized non-medical cannabis has led to growing concern over the potential adverse health impacts of cannabis consumption among youth and emerging adults. This study explored emerging adult perceptions of cannabis consumption and if perceptions changed based on the age and sex of the cannabis consumer. METHODS: Canadian emerging adults between the ages of 18 and 25 years (N = 1,424, Mean = 21.23) were randomly assigned to one of six vignettes that varied by age (14 years, 21 years, and 28 years) or sex (male, female) of the cannabis consumer. Participants were asked to rate seven single-item measures on perceived dangerousness, problematic consumption, negative impacts, and level of disapproval related to the vignette character's almost daily cannabis consumption. RESULTS: The results of seven 2 × 3 factorial analyses of variance revealed a main effect of age on six of seven items, no main effects of sex, and no interactions. Except for social life, participants noted significant differences in harms of cannabis consumption by 14-year-olds, compared to 21-year-olds and 28-year-olds. There were no significant differences in overall perceived dangerousness, problematic consumption, or impact on mental or cognitive health between 21-year-olds and 28-year-olds. Participants perceived cannabis consumption by a 21-year-old to be more harmful to brain development and reported greater disapproval than consumption by a 28-year-old. DISCUSSION: Emerging adults may appreciate the impacts of cannabis consumption within their age cohort on brain development and perceive greater risks for youth. Further education should focus on the potential cognitive and mental health impacts of cannabis in emerging adults.


Subject(s)
Cannabis , Adolescent , Humans , Adult , Male , Female , Young Adult , Cannabis/adverse effects , Sex Characteristics , Canada , Mental Health , Legislation, Drug
8.
BMC Public Health ; 22(1): 2384, 2022 12 19.
Article in English | MEDLINE | ID: mdl-36536347

ABSTRACT

BACKGROUND: Cannabis legalization is intended to protect the public from potential harm by restricting access and promoting greater awareness of cannabis-related risks. Youth are at a greater risk for experiencing road-related harms due to their own or others' use of cannabis. This qualitative research explored youths' perceptions about cannabis and road safety. METHODS: A qualitative study using focus groups (FG) was conducted with youth (age 13-18) and young adults (age 19-25) who resided in Newfoundland and Labrador. Using semi-structured interview questions, the facilitator asked participants to share their opinions about cannabis and road safety. All sessions were hosted virtually using Zoom with recruitment until saturation was met. All sessions were audio recorded, de-identified, and transcribed. Analysis utilized an inductive thematic approach informed by Braun and Clarke's (2006) method and inductive coding was facilitated using NVivo. RESULTS: Six youth (n = 38) and five young adult (n = 53) FG were conducted. Five prominent themes emerged throughout discussions across both age groups including: a) normalization of driving under the influence of cannabis, b) knowledge and awareness, c) perceptions of risk, d) modes of transportation, and e) detection. Variation in perceptions appeared to be influenced by lack of awareness of the impact of cannabis on driving ability, residence in urban versus rural locations, type of vehicle driven (e.g., car vs. off-road vehicles), and gender. CONCLUSION: The themes uncovered from this research will help inform future enhancement of cannabis policy to ensure the safety of all citizens. These findings will also support the inclusion of youth-focused education that will equip youth with informed decision-making strategies regarding road safety. Furthermore, these findings can be utilized to inform the refinement of cannabis driving policies to ensure the safety of all citizens on or off the road.


Subject(s)
Automobile Driving , Cannabis , Driving Under the Influence , Young Adult , Humans , Adolescent , Adult , Canada , Newfoundland and Labrador
9.
Can J Diabetes ; 44(1): 6-13, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31311729

ABSTRACT

OBJECTIVES: To estimate the strength of preferences, relative importance and trade-offs that patients with type 2 diabetes make between characteristics of antihyperglycemic medications. METHODS: We conducted a discrete choice experiment with a sample of Canadians with type 2 diabetes. Respondents completed 14 choice tasks and choose between 2 hypothetical drug alternatives, described by 8 characteristics (cost, efficacy, life expectancy, risk of macrovascular event, risk of microvascular event, risk of severe hypoglycemia, risk of minor side effects and risk of rare but serious side effects). An opt-out option was also provided. Characteristics used to describe the 2 drugs were identified using a literature review, focus groups and interviews. A multinomial mixed logit model was used to estimate choice probabilities. Willingness to pay (WTP) was used to assess trade-offs between characteristics. RESULTS: A total of 502 survey responses were included. The average age of participants was 59±12 years. Participants were 59% men, and 62% had diabetes for at least 6 years. All characteristics were found to significantly influence choice. On average, patients were willing to pay a monthly cost for their therapy of $134 to achieve 3 additional years of life; $49 and $36 for a 20% reduction in their risk of macrovascular and microvascular events, respectively; $34 for a 1% drop in glycated hemoglobin; $29 for a 50% less risk of severe hypoglycemia over 10 years; $29 for a 50% less risk of a minor side effect and $17 for a 50% less risk of a rare but serious side effect over 10 years. CONCLUSIONS: All 8 characteristics were shown to significantly influence choice, with cost and life expectancy carrying the most weight and serious and minor side effects carrying the least weight.


Subject(s)
Choice Behavior , Cost-Benefit Analysis , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/psychology , Hypoglycemic Agents/therapeutic use , Patient Preference/psychology , Patient Preference/statistics & numerical data , Adolescent , Adult , Aged , Diabetes Mellitus, Type 2/economics , Female , Follow-Up Studies , Humans , Hypoglycemia/prevention & control , Male , Middle Aged , Patient Acceptance of Health Care , Prognosis , Risk Assessment , Surveys and Questionnaires , Young Adult
10.
BMJ Open ; 9(1): e022577, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30813108

ABSTRACT

OBJECTIVE: To estimate the association between the use of sodium glucose co-transporter-2 (SGLT2) inhibitors and postmarket harms as identified by drug regulatory agencies. DESIGN: We conducted a systematic review and meta-analysis of randomised controlled trials (RCT). Six large databases were searched from inception to May 2018. Random effects models were used to estimate pooled relative risks (RRs). INTERVENTION: SGLT2 inhibitors, compared with placebo or active comparators. PRIMARY OUTCOMES: Acute kidney injury (AKI), diabetic ketoacidosis (DKA), urinary tract infections (UTI), bone fractures and lower limb amputations. RESULTS: We screened 2418 citations of which 109 were included. Most studies included one of four SGLT2 inhibitors, dapagliflozin, canagliflozin, empagliflozin and ipragliflozin. When compared with placebo, SGLT2 inhibitors were found to be significantly protective against AKI (RR=0.59; 95% CI 0.39 to 0.89; I2=0.0%), while no difference was found for DKA (RR 0.66; 95% CI 0.30 to 1.45, I2=0.0%), UTI (RR 1.02; 95% CI 0.95 to 1.09, I2=0.0%) or bone fracture (RR 0.87; 95% CI 0.69 to 1.09, I2=1.3%). Three studies reported on amputation, with one finding a significant increase risk. No increased risk for either outcome was found when compared with active controls. Subgroup analysis did show an increased risk of UTI with dapagliflozin only (RR 1.21; 95% CI 1.02 to 1.43, I2=0.0%), but no other analysis supported an increased risk of AKI, DKA, UTI or fracture. CONCLUSIONS: Current evidence from RCTs does not suggest an increased risk of harm with SGLT2 inhibitors as a class over placebo or active comparators with respect to AKI, DKA, UTI or fracture. However, wide CIs for many comparisons suggest limited precision, and therefore clinically important adverse events cannot be ruled out. Dapagliflozin, appears to independently increase the risk of UTI, although the mechanism for this intraclass variation in risk is unclear. PROSPERO REGISTRATION NUMBER: CRD42016038715.


Subject(s)
Acute Kidney Injury/chemically induced , Diabetic Ketoacidosis/chemically induced , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Urinary Tract Infections/chemically induced , Amputation, Surgical , Benzhydryl Compounds , Canagliflozin , Fractures, Bone/chemically induced , Glucosides , Humans , Randomized Controlled Trials as Topic , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Thiophenes
11.
CMAJ Open ; 6(4): E594-E602, 2018.
Article in English | MEDLINE | ID: mdl-30530719

ABSTRACT

BACKGROUND: The sodium glucose cotransporter-2 (SGLT2) inhibitors are a novel group of drugs for treatment of type 2 diabetes mellitus. We investigated whether there is a dose-response relation between SGLT2 inhibitors and urinary tract infections (UTIs) in patients with type 2 diabetes, relative to other diabetes therapies or placebo. METHODS: We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) of SGLT2 inhibitors in patients with type 2 diabetes. We searched 6 databases and the reference lists of key papers. We included studies with placebo or active antidiabetic comparators that reported the outcome of UTI, and established thresholds for high and low doses of SGLT2 inhibitors. We used a random-effects model to estimate the pooled effect estimates and 95% credible intervals. RESULTS: We screened 2418 citations and included 105 references for studies of 8 unique SGLT2 inhibitors, representing 60 082 individuals (with a total of 4348 UTIs). Most mixed-treatment comparisons showed no significant difference in risk of UTI, with the exception of high-dose dapagliflozin (≥ 10 mg) compared with placebo (odds ratio [OR] 1.30, 95% credible interval 1.09-1.57), with active comparators (OR 1.44, 95% credible interval 1.15-1.79), with empagliflozin at both low (OR 1.30, 95% credible interval 1.04-1.60) and high (OR 1.39, 95% credible interval 1.12-1.72) doses, and with low-dose ertugliflozin (OR 1.43, 95% credible interval 1.01-2.01). When the analysis was restricted to RCTs with a low risk of bias, the results were nonsignificant. INTERPRETATION: Current RCT evidence does not suggest a dose-response relation between most SGLT2 inhibitors and UTIs, with the exception of dapagliflozin. Further research is needed to quantify the relation between SGLT2 inhibitors and more serious infections. TRIAL REGISTRATION: PROSPERO registration no. CRD42016038715.

12.
Sci Rep ; 8(1): 15142, 2018 10 11.
Article in English | MEDLINE | ID: mdl-30310100

ABSTRACT

Although the glucose lowering effect of dipeptidyl peptidase-4 (DPP4) inhibitors is well established, several potential serious acute safety concerns have been raised including acute kidney injury, respiratory tract infections, and acute pancreatitis. Using the UK-based Clinical Practice Research Datalink (CPRD), we identified initiators (365-day washout period) of DPP4 inhibitors and relevant comparators including initiators of sulfonylureas, metformin, thiazolidinediones, and insulin between January 2007 and January 2016 to quantify the association between DPP4 inhibitors and three acute health events - acute kidney injury, respiratory tract infections, and acute pancreatitis. The associations between drug and study outcomes were estimated using Cox proportional hazard models adjusted for deciles of high-dimensional propensity scores and number of additional glucose lowering agents. After controlling for potential confounders, the risk was not significantly increased or decreased for initiators of DPP4 inhibitors compared to sulfonylureas (hazard ratio (HR) [95% confidence interval (CI)] for acute kidney injury: 0.81 [0.56-1.18]; HR for respiratory tract infections: 0.93 [0.84-1.04]; HR for acute pancreatitis 1.03 [0.42-2.52], metformin (HR for respiratory tract infection 0.91 [0.65-1.27]), thiazolidinediones (HR for acute kidney injury: 1.12 [0.60-2.10]; HR for respiratory tract infections: 1.02 [0.86-1.21]; HR for acute pancreatitis: 1.21 [0.25-5.72]), or insulin (HR for acute kidney injury: 1.40 [0.77-2.55]; HR for respiratory tract infections: 0.74 [0.60-0.92]; HR for acute pancreatitis: 1.01 [0.24-4.19]). Initiators of DPP4 inhibitors were associated with an increased risk of acute kidney injury when compared to metformin initiators (HR [95% CI] for acute kidney injury: 1.85 [1.10-3.12], although this association was attenuated when DPP4 inhibitor monotherapy was compared to metformin monotherapy exposure as a time-dependent variable (HR 1.39 [0.91-2.11]). Initiation of a DPP4 inhibitor was not associated with an increased risk of acute kidney injury, respiratory tract infections, or acute pancreatitis compared to sulfonylureas or other glucose-lowering therapies.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Hypoglycemic Agents/adverse effects , Sulfonylurea Compounds/adverse effects , Aged , Blood Glucose , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Female , Humans , Hypoglycemic Agents/therapeutic use , Infections/etiology , Male , Middle Aged , Proportional Hazards Models , Sulfonylurea Compounds/therapeutic use
13.
J Am Med Inform Assoc ; 25(9): 1240-1247, 2018 09 01.
Article in English | MEDLINE | ID: mdl-29982512

ABSTRACT

Objective: To identify and describe clinical drug data sources that have the potential to serve as a repository of information for developing drug knowledge translation products. Methods: Two reviewers independently screened citations from PubMed and Embase, websites from the web search engine Google, and references from selected journals. Publicly licensed or non-proprietary data sources containing clinical drug information accessible in a machine-readable format were eligible. Data sources were assessed for their coverage across 18 pre-specified domains and 74 elements of clinical drug information. Results: Of the 3369 unique citations or webpages screened, 44 drug information data sources were identified. Of these, 22 data sources met the study inclusion criteria. There was a mean of 4.5 (SD = 5.19) domains covered by each source and a mean of 10.9 (SD = 18) elements covered by each source. None of the data sources covered all domains and eight elements were not addressed by any source. All of the data sources identified by the study are government or academic databases. Conclusion: Our study demonstrated the availability of machine-readable clinical drug data that could help facilitate the creation of novel drug knowledge translation products. However, we identified clinical content gaps in the available non-proprietary drug information sources. Further evaluation of the quality of each data source would be necessary prior to incorporating these sources into any knowledge translation products intended for clinical use.


Subject(s)
Databases, Factual , Drug Therapy , Pharmaceutical Preparations , Translational Research, Biomedical/methods , Drug Interactions , Drug-Related Side Effects and Adverse Reactions , Humans
14.
Diabetes Res Clin Pract ; 136: 159-167, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29258886

ABSTRACT

AIMS: Mixed evidence exists for the effect of incretin-based therapies on osteoporosis in type-2 diabetes. Therefore, we conducted a cohort study to determine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and common osteoporotic "fragility fractures" (upper extremity, hip, spine). METHODS: The UK-based Clinical Practice Research Datalink was used to identify adults without prior fractures receiving a new anti-diabetic drug or a new type-2 diabetes diagnosis between 2007 and 2016. The primary aim was to compare new-users of DPP-4 inhibitors versus new-users of sulfonylureas (SU). The association between DPP-4 inhibitors and incident fractures was estimated using Cox proportional hazards models. Deciles of high-dimensional propensity scores and other anti-diabetic drugs were used as covariates. RESULTS: We identified 7993 and 26,636 new-users of DPP-4 inhibitors and SUs, respectively. At cohort entry, the mean age was 58.8, 40% were female, mean diabetes duration was 1.3 years, and 42% had A1c > 9%. Over 9 years (mean follow-up = 1.2 years), the incident rate of fragility fractures was lower among DPP-4 versus SU users (3.0/1000 vs. 5.2/1000 person-years; P-value = 0.007). After adjustment, there was no statistically significant difference in fracture risk (hazard ratio adjusted, aHR = 0.80, 95%CI 0.51-1.24; P-value = 0.3125). In a secondary analysis, DPP-4 inhibitors were not associated with a difference in fracture risk compared to insulin (aHR = 0.91, 95%CI 0.40-2.09); however were associated with a lower fracture risk versus thiazolidinediones (aHR = 0.47, 95%CI 0.26-0.83). Sensitivity analyses supported findings. CONCLUSIONS: DPP-4 inhibitors are not associated with an increased risk of fragility fractures compared with SUs or insulin; however, are associated with a lower risk versus thiazolidinediones.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Fractures, Bone/chemically induced , Cohort Studies , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Female , Humans , Male , Middle Aged , Risk
15.
Pediatr Blood Cancer ; 57(2): 231-9, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21344614

ABSTRACT

BACKGROUND: An increased understanding of the genetic basis of disease creates a demand for personalized medicine and more genetic testing for diagnosis and treatment. The objective was to assess the incremental cost-effectiveness per life-month gained of thiopurine methyltransferase (TPMT) genotyping to guide doses of 6-mercaptopurine (6-MP) in children with acute lymphoblastic leukemia (ALL) compared to enzymatic testing and standard weight-based dosing. PROCEDURE: A cost-effectiveness analysis was conducted from a health care system perspective comparing costs and consequences over 3 months. Decision analysis was used to evaluate the impact of TPMT tests on preventing myelosuppression and improving survival in ALL patients receiving 6-MP. Direct medical costs included laboratory tests, medications, physician services, pharmacy and inpatient care. Probabilities were derived from published evidence. Survival was measured in life-months. The robustness of the results to variable uncertainty was tested in one-way sensitivity analyses. Probabilistic sensitivity analysis examined the impact of parameter uncertainty and generated confidence intervals around point estimates. RESULTS: Neither of the testing interventions showed a benefit in survival compared to weight-based dosing. Both test strategies were more costly compared to weight-based dosing. Incremental costs per child (95% confidence interval) were $277 ($112, $442) and $298 ($392, $421) for the genotyping and phenotyping strategies, respectively, compared to weight-based dosing. CONCLUSIONS: The present analysis suggests that screening for TPMT mutations using either genotype or enzymatic laboratory tests prior to the administration of 6-MP in pediatric ALL patients is not cost-effective.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Clinical Enzyme Tests/economics , Genetic Testing/economics , Mercaptopurine/administration & dosage , Methyltransferases/deficiency , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/enzymology , Antimetabolites, Antineoplastic/adverse effects , Bone Marrow Diseases/chemically induced , Bone Marrow Diseases/prevention & control , Child, Preschool , Cost-Benefit Analysis , Decision Trees , Drug Dosage Calculations , Genotype , Humans , Mercaptopurine/adverse effects , Methyltransferases/genetics , Models, Econometric , Ontario , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Sensitivity and Specificity , Survival Analysis
16.
Ther Drug Monit ; 33(2): 192-9, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21240057

ABSTRACT

BACKGROUND: An increased understanding of the genetic basis of disease creates a demand for personalized medicine and more accurate testing for diagnosis and treatment. Thiopurine methyltransferase (TPMT) plays an important role in the metabolism of thiopurine drugs used in pediatric leukemia, rheumatoid arthritis, and inflammatory bowel disease. The objective was to review the literature systematically to ascertain the performance characteristics of current genotype and enzymatic testing technologies for TPMT. METHODS: A systematic review of the literature was conducted to describe TPMT testing technologies. Eligible studies evaluated either a TPMT genotype or TPMT phenotype technology in comparison to a reference standard and expressed results in terms of sensitivity and specificity or positive/negative predictive value. The laboratory technique was recorded, and the quality of the identified studies was assessed using a modified Critical Appraisal Skills Program tool. RESULTS: Seventeen studies were reviewed. The sensitivity and specificity of the genotype test ranged from 55% to 100% and from 94% to 100%, respectively. The sensitivity and specificity of the phenotype test ranged from 92% to 100% and from 86% to 98%, respectively. A variety of laboratory techniques were employed. Reviewed studies were of low methodological quality. CONCLUSIONS: The systematic review of TPMT test strategies found that available technologies demonstrated high values for sensitivity and specificity, however, there was a lack of a single gold standard and most studies were of poor quality. Disregard for study sample size and confounding factors such as concurrent medications and blood transfusions were the main contributors to low quality. There were also inconsistencies in the selection of a reference standard which complicated the interpretation of the findings.


Subject(s)
Methyltransferases/deficiency , Methyltransferases/metabolism , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/genetics , Child , Clinical Enzyme Tests , Genotype , Humans , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/genetics , Leukemia/drug therapy , Leukemia/genetics , Methyltransferases/genetics , Research Design , Sensitivity and Specificity
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