Comparative efficacy of sodium-glucose co-transporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists in chronic kidney disease and type 2 diabetes: A systematic review and network meta-analysis.

AIM: To compare the relative efficacy of sodium-glucose co-transporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs) and non-steroidal mineralocorticoid receptor antagonists (nsMRAs) in improving the cardiovascular and renal outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). MATERIALS AND METHODS: We searched PubMed, Embase and Cochrane Library from inception through 25 November 2022. We selected randomized controlled trials that studied patients with CKD and T2D with a follow-up of at least 24 weeks and compared SGLT-2is, GLP-1RAs and nsMRAs with each other and with placebo. Primary outcomes were major adverse cardiovascular events (MACE) and composite renal outcomes (CRO). Secondary outcomes were cardiovascular death, all-cause death, stroke, myocardial infarction and heart failure hospitalization (HFH). A frequentist approach was used to pool risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Twenty-nine studies with 50 938 participants for MACE and 49 965 participants for CRO were included. SGLT-2is did not significantly reduce MACE but were associated with significantly lower risks of CRO compared with GLP-1RAs (RR, 0.77; 95% CI, 0.64-0.91; P = .003) and nsMRAs (RR, 0.78; 95% CI, 0.68-0.90; P = .001). Compared with GLP-1RAs and nsMRAs, SGLT-2is significantly reduced risks of HFH by 31% (RR, 0.69; 95% CI, 0.55-0.88; P = .002) and 22% (RR, 0.78; 95% CI, 0.63-0.95; P = .016), respectively, but did not significantly reduce other secondary outcomes. There were no significant differences between GLP-1RAs and nsMRAs in lowering all outcomes. CONCLUSIONS: SGLT-2is were associated with better cardiorenal protection than GLP-1RAs and nsMRAs in patients with CKD and T2D.

Cost-effectiveness of canagliflozin and dapagliflozin for treatment of patients with chronic kidney disease and type 2 diabetes.

AIM: To examine the cost-effectiveness of adding canagliflozin or dapagliflozin to standard of care (SoC) versus SoC alone in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). MATERIALS AND METHODS: We used a Markov microsimulation model to assess the cost-effectiveness of canagliflozin plus SoC (canagliflozin + SoC), dapagliflozin plus SoC (dapagliflozin + SoC) and SoC alone. Analyses were conducted from a healthcare system perspective. Costs were measured in 2021 Canadian dollars (C$), and effectiveness was measured in quality-adjusted life-years (QALYs). RESULTS: Over a patient's lifetime, canagliflozin + SoC and dapagliflozin + SoC yielded cost savings of C$33 460 and C$26 764 and generated 1.38 and 1.44 additional QALYs compared with SoC alone, respectively. While QALY gains with dapagliflozin + SoC were higher than those with canagliflozin + SoC, this strategy was also more costly with the incremental cost-effectiveness ratio exceeding the willingness to pay threshold of C$50 000 per QALY. Dapagliflozin + SoC, however, generated cost savings and QALY gains compared with canagliflozin + SoC over shorter time horizons of 5 or 10 years. CONCLUSIONS: Dapagliflozin + SoC was not cost-effective versus canagliflozin + SoC in patients with CKD and T2D over the lifetime horizon. However, adding canagliflozin or dapagliflozin to SoC was less costly and more effective relative to SoC alone for treatment of CKD and T2D.

Cost-effectiveness of using artificial intelligence versus polygenic risk score to guide breast cancer screening.

BACKGROUND: Current guidelines for mammography screening for breast cancer vary across agencies, especially for women aged 40-49. Using artificial Intelligence (AI) to read mammography images has been shown to predict breast cancer risk with higher accuracy than alternative approaches including polygenic risk scores (PRS), raising the question whether AI-based screening is more cost-effective than screening based on PRS or existing guidelines. This study provides the first evidence to shed light on this important question. METHODS: This study is a model-based economic evaluation. We used a hybrid decision tree/microsimulation model to compare the cost-effectiveness of eight strategies of mammography screening for women aged 40-49 (screening beyond age 50 follows existing guidelines). Six of these strategies were defined by combinations of risk prediction approaches (AI, PRS or family history) and screening frequency for low-risk women (no screening or biennial screening). The other two strategies involved annual screening for all women and no screening, respectively. Data used to populate the model were sourced from the published literature. RESULTS: Risk prediction using AI followed by no screening for low-risk women is the most cost-effective strategy. It dominates (i.e., costs more and generates fewer quality adjusted life years (QALYs)) strategies for risk prediction using PRS followed by no screening or biennial screening for low-risk women, risk prediction using AI or family history followed by biennial screening for low-risk women, and annual screening for all women. It also extendedly dominates (i.e., achieves higher QALYs at a lower incremental cost per QALY) the strategy for risk prediction using family history followed by no screening for low-risk women. Meanwhile, it is cost-effective versus no screening, with an incremental cost-effectiveness ratio of $23,755 per QALY gained. CONCLUSIONS: Risk prediction using AI followed by no breast cancer screening for low-risk women is the most cost-effective strategy. This finding can be explained by AI's ability to identify high-risk women more accurately than PRS and family history (which reduces the possibility of delayed breast cancer diagnosis) and fewer false-positive diagnoses from not screening low-risk women.

Too young for Cannabis? Choice of minimum legal age for legalized non-medical Cannabis in Canada.

BACKGROUND: Choice of minimum legal age (MLA) for cannabis use is a critical and contentious issue in legalization of non-medical cannabis. In Canada where non-medical cannabis was recently legalized in October 2018, the federal government recommended age 18, the medical community argued for 21 or even 25, while public consultations led most Canadian provinces to adopt age 19. However, no research has compared later life outcomes of first using cannabis at these different ages to assess their merits as MLAs. METHODS: We used doubly robust regression techniques and data from nationally representative Canadian surveys to compare educational attainment, cigarette smoking, self-reported general and mental health associated with different ages of first cannabis use. RESULTS: We found different MLAs for different outcomes: 21 for educational attainment, 19 for cigarette smoking and mental health and 18 for general health. Assuming equal weight for these individual outcomes, the 'overall' MLA for cannabis use was estimated to be 19 years. Our results were robust to various robustness checks. CONCLUSION: Our study indicated that there is merit in setting 19 years as MLA for non-medical cannabis.

Incremental Cost-Effectiveness of Aspiration Therapy vs Bariatric Surgery and No Treatment for Morbid Obesity.

INTRODUCTION: Despite its recent approval by the US Food and Drug Administration and Health Canada, aspiration therapy-one of the latest weight loss treatments-remains controversial. Critics have expressed concerns that the therapy could lead to bulimia and other binge eating disorders. Meanwhile, proponents argue that the therapy is less invasive, reversible, and cheaper than bariatric surgery. Cost-effectiveness of this therapy, however, is not yet established. METHODS: We developed a Markov model to estimate the incremental cost-effectiveness of aspiration therapy relative to 2 most common bariatric surgery procedures (gastric bypass and sleeve gastrectomy) and no treatment over a lifetime horizon. Costs were estimated from the health system's perspective using US data. Effectiveness was measured in terms of quality-adjusted life-years (QALYs). RESULTS: Despite being a cheaper procedure than bariatric surgery, aspiration therapy costs more than bariatric surgery in the long term because of its high maintenance costs (i.e., periodic replacement of device parts). It also yields lower QALYs than bariatric surgery because of its smaller weight loss effects. Thus, the therapy is dominated by bariatric surgery. In particular, compared with gastric bypass, it costs US$5,318 more and yields 1.31 fewer QALYs. However, aspiration therapy is cost-effective relative to no treatment with an incremental cost-effectiveness ratio of US$17,532 per QALY gained. DISCUSSION: Given its high lifetime costs and its modest weight loss effects, aspiration therapy is not cost-effective relative to bariatric surgery. However, it is a cost-effective treatment option for patients who lack access to bariatric surgery.

Incremental cost-effectiveness of algorithm-driven genetic testing versus no testing for Maturity Onset Diabetes of the Young (MODY) in Singapore.

BACKGROUND: Offering genetic testing for Maturity Onset Diabetes of the Young (MODY) to all young patients with type 2 diabetes has been shown to be not cost-effective. This study tests whether a novel algorithm-driven genetic testing strategy for MODY is incrementally cost-effective relative to the setting of no testing. METHODS: A decision tree was constructed to estimate the costs and effectiveness of the algorithm-driven MODY testing strategy and a strategy of no genetic testing over a 30-year time horizon from a payer's perspective. The algorithm uses glutamic acid decarboxylase (GAD) antibody testing (negative antibodies), age of onset of diabetes (<45 years) and body mass index (<25 kg/m2 if diagnosed >30 years) to stratify the population of patients with diabetes into three subgroups, and testing for MODY only among the subgroup most likely to have the mutation. Singapore-specific costs and prevalence of MODY obtained from local studies and utility values sourced from the literature are used to populate the model. RESULTS: The algorithm-driven MODY testing strategy has an incremental cost-effectiveness ratio of US$93 663 per quality-adjusted life year relative to the no testing strategy. If the price of genetic testing falls from US$1050 to US$530 (a 50% decrease), it will become cost-effective. CONCLUSION: Our proposed algorithm-driven testing strategy for MODY is not yet cost-effective based on established benchmarks. However, as genetic testing prices continue to fall, this strategy is likely to become cost-effective in the near future.

Association between asthma control and asthma cost: Results from a longitudinal study in a primary care setting.

BACKGROUND AND OBJECTIVE: Asthma control can be assessed with the Asthma Control Test (ACT) and a score of 20 or higher indicates good asthma control. Patients pay for their consultation and treatment in the fee-for-service primary healthcare system in Singapore. We hypothesized that achieving asthma control would result in lower asthma costs through reduced acute exacerbations, fewer physician consultations and lower lost productivity. The study compared the healthcare costs of patients who achieved asthma control and those with suboptimal asthma control based on ACT scores. Factors influencing asthma control and healthcare expenditure over time were also examined. METHODS: A total of 736 patients were enrolled into an asthma care programme in two polyclinics during 2008 and 2013. Direct costs of asthma management were derived from the frequency of polyclinic consultations, medication costs and hospitalization. Indirect costs were estimated from lost workdays due to exacerbations. The generalized estimating equation (GEE) approach was used to longitudinally model the factors associated with total healthcare expenditure. RESULTS: Patients with asthma control spent S$48 (US$36) more per doctor visit on asthma drugs (P < 0.01) but incurred S$65 (US$48) less per doctor visit in total costs (P < 0.01) than those with suboptimal asthma control. The savings from achieving asthma control for obese patients were greater than for normal-weight patients (S$42 or the equivalent of US$31; P < 0.05). CONCLUSION: Optimal asthma control was associated with reduced healthcare costs. An effective treatment regimen should also consider other modifiable factors such as weight control to achieve asthma control and eventually reduce asthma costs.

Is bronchial thermoplasty cost-effective as treatment for problematic asthma patients? Singapore's perspective on a global model.

BACKGROUND AND OBJECTIVE: Bronchial thermoplasty (BT) has been shown to be effective at reducing asthma exacerbations and improving asthma control for patients with severe persistent asthma but it is also expensive. Evidence on its cost-effectiveness is limited and inconclusive. In this study, we aim to evaluate the incremental cost-effectiveness of BT combined with optimized asthma therapy (BT-OAT) relative to OAT for difficult-to-treat and severe asthma patients in Singapore, and to provide a general framework for determining BT's cost-effectiveness in other healthcare settings. METHODS: We developed a Markov model to estimate the costs and quality-adjusted life years (QALYs) gained with BT-OAT versus OAT from the societal and health system perspectives. The model was populated using Singapore-specific costs and transition probabilities and utilities from the literature. Sensitivity analyses were conducted to identify the main factors determining cost-effectiveness of BT-OAT. RESULTS: BT-OAT is not cost-effective relative to OAT over a 5-year time horizon with an incremental cost-effectiveness ratio (ICER) of $US138 889 per QALY from the societal perspective and $US139 041 per QALY from the health system perspective. The cost-effectiveness of BT-OAT largely depends on a combination of the cost of the BT procedure and the cost of asthma-related hospitalizations and emergency department (ED) visits. CONCLUSION: Based on established thresholds for cost-effectiveness, BT-OAT is not cost-effective compared with OAT in Singapore. Given its current clinical efficacy, BT-OAT is most likely to be cost-effective in a setting where the cost of BT procedure is low and costs of hospitalization and ED visits are high.

Cost-effectiveness of a National Telemedicine Diabetic Retinopathy Screening Program in Singapore.

PURPOSE: To determine the incremental cost-effectiveness of a new telemedicine technician-based assessment relative to an existing model of family physician (FP)-based assessment of diabetic retinopathy (DR) in Singapore from the health system and societal perspectives. DESIGN: Model-based, cost-effectiveness analysis of the Singapore Integrated Diabetic Retinopathy Program (SiDRP). PARTICIPANTS: A hypothetical cohort of patients aged 55 years with type 2 diabetes previously not screened for DR. METHODS: The SiDRP is a new telemedicine-based DR screening program using trained technicians to assess retinal photographs. We compared the cost-effectiveness of SiDRP with the existing model in which FPs assess photographs. We developed a hybrid decision tree/Markov model to simulate the costs, effectiveness, and incremental cost-effectiveness ratio (ICER) of SiDRP relative to FP-based DR screening over a lifetime horizon. We estimated the costs from the health system and societal perspectives. Effectiveness was measured in terms of quality-adjusted life-years (QALYs). Result robustness was calculated using deterministic and probabilistic sensitivity analyses. MAIN OUTCOME MEASURES: The ICER. RESULTS: From the societal perspective that takes into account all costs and effects, the telemedicine-based DR screening model had significantly lower costs (total cost savings of S$173 per person) while generating similar QALYs compared with the physician-based model (i.e., 13.1 QALYs). From the health system perspective that includes only direct medical costs, the cost savings are S$144 per person. By extrapolating these data to approximately 170 000 patients with diabetes currently being screened yearly for DR in Singapore's primary care polyclinics, the present value of future cost savings associated with the telemedicine-based model is estimated to be S$29.4 million over a lifetime horizon. CONCLUSIONS: While generating similar health outcomes, the telemedicine-based DR screening using technicians in the primary care setting saves costs for Singapore compared with the FP model. Our data provide a strong economic rationale to expand the telemedicine-based DR screening program in Singapore and elsewhere.

Changes in Medical Cannabis Use After Recreational Cannabis Legalization in Canada.

Background: As part of its recreational cannabis legalization in October 2018, Canada imposed an excise tax of 10% (or $1 a gram, whichever is higher) on both recreational and medical cannabis. There is little evidence to inform the ongoing debate on whether the legalization had adverse impacts on medical cannabis use. Methods: We used an interrupted time series design and data on medical cannabis shipments (i.e., mail-order deliveries of cannabis from a licensed producer to a patient authorized to obtain medical cannabis) in Canada between quarter 1 of 2014 and quarter 1 of 2020. We examined changes in medical cannabis shipments after Canada's recreational cannabis legalization both across Canada and for each province. As this study used publicly available, province-level aggregate data, ethics approval was not required. Results: Recreational cannabis legalization was associated with significant reductions in medical cannabis use in 7 out of 10 Canadian provinces. Compared with the counterfactual estimated from prelegalization trends, the reduction in quarter 1 of 2020 varied from 500 shipments per 100,000 population (95% CI=312-688 shipments per 100,000 population) or 32% (95% CI=22-43%) in Newfoundland and Labrador to 3,778 shipments per 100,000 population (95% CI=2,972-4,585 shipments per 100,000 population) or 74% (95% CI=68-79%) in Alberta. At the national level, the number of medical cannabis shipments decreased by 823 per 100,000 population (95% CI=725-921 shipments per 100,000 population) or 48% (95% CI=45-52%). Conclusions: Recreational cannabis legalization was associated with reductions in medical cannabis use. Our findings call for policy attention to address possible adverse impacts of recreational cannabis legalization on medical cannabis users.

Recreational and Medical Cannabis Legalization and Opioid Prescriptions and Mortality.

Importance: While some have argued that cannabis legalization has helped to reduce opioid-related morbidity and mortality in the US, evidence has been mixed. Moreover, existing studies did not account for biases that could arise when policy effects vary over time or across states or when multiple policies are assessed at the same time, as in the case of recreational and medical cannabis legalization. Objective: To quantify changes in opioid prescriptions and opioid overdose deaths associated with recreational and medical cannabis legalization in the US. Design, Setting, and Participants: This quasiexperimental, generalized difference-in-differences analysis used annual state-level data between January 2006 and December 2020 to compare states that legalized recreational or medical cannabis vs those that did not. Intervention: Recreational and medical cannabis law implementation (proxied by recreational and medical cannabis dispensary openings) between 2006 and 2020 across US states. Main Outcomes and Measures: Opioid prescription rates per 100 persons and opioid overdose deaths per 100 000 population based on data from the US Centers for Disease Control and Prevention. Results: Between 2006 and 2020, 13 states legalized recreational cannabis and 23 states legalized medical cannabis. There was no statistically significant association of recreational or medical cannabis laws with opioid prescriptions or overall opioid overdose mortality across the 15-year study period, although the results also suggested a potential reduction in synthetic opioid deaths associated with recreational cannabis laws (4.9 fewer deaths per 100 000 population; 95% CI, -9.49 to -0.30; P = .04). Sensitivity analyses excluding state economic indicators, accounting for additional opioid laws and using alternative ways to code treatment dates yielded substantively similar results, suggesting the absence of statistically significant associations between cannabis laws and the outcomes of interest during the full study period. Conclusions and Relevance: The results of this study suggest that, after accounting for biases due to possible heterogeneous effects and simultaneous assessment of recreational and medical cannabis legalization, the implementation of recreational or medical cannabis laws was not associated with opioid prescriptions or opioid mortality, with the exception of a possible reduction in synthetic opioid deaths associated with recreational cannabis law implementation.

Cost-Effectiveness of Lecanemab for Individuals With Early-Stage Alzheimer Disease.

BACKGROUND AND OBJECTIVES: Little is known regarding the cost-effectiveness of lecanemab (Leqembi), a monoclonal antibody approved by the US Food and Drug Administration in January 2023 for the treatment of mild cognitive impairment (MCI) or mild dementia due to Alzheimer disease (AD). This study aims to quantify the cost-effectiveness of lecanemab and how it varies based on the accuracy of AD testing and individuals' APOE ε4 status. METHODS: Seven alternative test-treat-target strategies defined by combinations of testing approaches (PET, CSF, or plasma assay), treatment choices (standard of care [SoC] alone or lecanemab in addition to SoC), and targeting strategies (targeting APOE ε4 noncarriers or heterozygous patients or not) were compared. A hybrid decision tree-Markov cohort model was constructed with 5 states: (1) MCI (Clinical Dementia Rating-Sum of Boxes [CDR-SB] 0-4.5); (2) mild dementia (CDR-SB 4.6-9.5); (3) moderate dementia (CDR-SB 9.6-16); (4) severe dementia (CDR-SB >16); and (5) death. Effectiveness was measured by quality-adjusted life years and costs from third-party and societal perspectives were estimated in 2022 US dollars over a lifetime horizon. RESULTS: Among the 7 test-treat-target strategies, SoC alone was the optimal strategy from a cost-effectiveness perspective. Neither targeted lecanemab treatment nor treatment unrestricted by APOE ε4 genotype was cost-effective vs SoC alone, regardless of the test used to diagnose patients with early-stage AD. However, CSF assay followed by targeted treatment would become cost-effective if lecanemab is priced below $5,100 per year. These results were robust to the accuracy of diagnostic testing and rates of lecanemab discontinuation and adverse events. DISCUSSION: Neither targeted lecanemab treatment nor treatment unrestricted by APOE ε4 genotype is cost-effective vs SoC alone for patients with MCI or mild dementia due to AD. Lecanemab would be cost-effective in some settings if priced below $5,100 per year.

Association between non-medical cannabis legalization and alcohol sales: Quasi-experimental evidence from Canada.

BACKGROUND: There is increasing interest in understanding the impact of non-medical cannabis legalization on use of other substances, especially alcohol. Evidence on whether cannabis is a substitute or complement for alcohol is both mixed and limited. This study provides the first quasi-experimental evidence on the impact of Canada's legalization of non-medical cannabis on beer and spirits sales. METHODS: We used the interrupted time series design and monthly data on beer sales between January 2012 and February 2020 and spirits sales between January 2016 and February 2020 across Canada to investigate changes in beer and spirits sales following Canada's cannabis legalization in October 2018. We examined changes in total sales, nationally and in individual provinces, as well as changes in sales of bottled, canned and kegged beer. RESULTS: Canada-wide beer sales fell by 96 hectoliters per 100,000 population (p=0.011) immediately after non-medical cannabis legalization and by 4 hectoliters per 100,000 population (p>0.05) each month thereafter for an average monthly reduction of 136 hectoliters per 100,000 population (p<0.001) post-legalization. However, the legalization was associated with no change in spirits sales. Beer sales reduced in all provinces except the Atlantic provinces. By beer type, the legalization was associated with declines in sales of canned and kegged beer but there was no reduction in sales of bottled beer. CONCLUSIONS: Non-medical cannabis legalization was associated with a decline in beer sales in Canada, suggesting substitution of non-medical cannabis for beer. However, there was no change in spirits sales following the legalization.

British Columbia's Safer Opioid Supply Policy and Opioid Outcomes.

Importance: In March 2020, British Columbia, Canada, became the first jurisdiction globally to launch a large-scale provincewide safer supply policy. The policy allowed individuals with opioid use disorder at high risk of overdose or poisoning to receive pharmaceutical-grade opioids prescribed by a physician or nurse practitioner, but to date, opioid-related outcomes after policy implementation have not been explored. Objective: To investigate the association of British Columbia's Safer Opioid Supply policy with opioid prescribing and opioid-related health outcomes. Design, Setting, and Participants: This cohort study used quarterly province-level data from quarter 1 of 2016 (January 1, 2016) to quarter 1 of 2022 (March 31, 2022), from British Columbia, where the Safer Opioid Supply policy was implemented, and Manitoba and Saskatchewan, where the policy was not implemented (comparison provinces). Exposure: Safer Opioid Supply policy implemented in British Columbia in March 2020. Main Outcomes and Measures: The main outcomes were rates of prescriptions, claimants, and prescribers of opioids targeted by the Safer Opioid Supply policy (hydromorphone, morphine, oxycodone, and fentanyl); opioid-related poisoning hospitalizations; and deaths from apparent opioid toxicity. Difference-in-differences analysis was used to compare changes in outcomes before and after policy implementation in British Columbia with those in the comparison provinces. Results: The Safer Opioid Supply policy was associated with statistically significant increases in rates of opioid prescriptions (2619.6 per 100 000 population; 95% CI, 1322.1-3917.0 per 100 000 population; P < .001) and claimants (176.4 per 100 000 population; 95% CI, 33.5-319.4 per 100 000 population; P = .02). There was no significant change in prescribers (15.7 per 100 000 population; 95% CI, -0.2 to 31.6 per 100 000 population; P = .053). However, the opioid-related poisoning hospitalization rate increased by 3.2 per 100 000 population (95% CI, 0.9-5.6 per 100 000 population; P = .01) after policy implementation. There were no statistically significant changes in deaths from apparent opioid toxicity (1.6 per 100 000 population; 95% CI, -1.3 to 4.5 per 100 000 population; P = .26). Conclusions and Relevance: Two years after its launch, the Safer Opioid Supply policy in British Columbia was associated with higher rates of safer supply opioid prescribing but also with a significant increase in opioid-related poisoning hospitalizations. These findings will help inform ongoing debates about this policy not only in British Columbia but also in other jurisdictions that are contemplating it.

Cost-Effectiveness of Antiobesity Drugs for Adolescents With Severe Obesity.

Importance: Although the American Academy of Pediatrics has recommended treatment with antiobesity drugs for adolescents, the cost-effectiveness of antiobesity drugs for this population is still unknown. Objective: To quantify cost-effectiveness of different antiobesity drugs available for pediatric use. Design, Setting, and Participants: This economic evaluation used a Markov microsimulation model with health states defined by obesity levels. Effectiveness was measured by quality-adjusted life-years (QALYs) and costs were calculated from third-party payer perspective, estimated in 2023 US dollars over a 10-year horizon. Data were obtained from the published literature. Intervention: Antiobesity drugs orlistat, liraglutide, semaglutide, and phentermine-topiramate vs no treatment. Metformin hydrochloride and 2 types of bariatric surgical procedures (sleeve gastrectomy and gastric bypass) were considered in sensitivity analysis. Main Outcomes and Measures: Incremental cost-effectiveness ratio. Results: Among the 4 antiobesity drugs currently approved for pediatric use, phentermine-topiramate was the most cost-effective with an incremental cost-effectiveness ratio of $93 620 per QALY relative to no treatment in this simulated cohort of 10 000 adolescents aged 12 to 17 years (mode, 15 years) with severe obesity (62% female). While semaglutide offered more QALYs than phentermine-topiramate, its higher cost resulted in an incremental cost-effectiveness ratio ($1 079 480/QALY) that exceeded the commonly used willingness-to-pay threshold of $100 000 to $150 000/QALY. Orlistat and liraglutide cost more and were less effective than phentermine-topiramate and semaglutide, respectively. Sleeve gastrectomy and gastric bypass were more effective than phentermine-topiramate but were also more costly, rendering them not cost-effective compared with phentermine-topiramate at the willingness-to-pay threshold of $100 000 to $150 000/QALY. Conclusions and Relevance: In this economic evaluation of weight loss drugs for adolescents with severe obesity, we found phentermine-topiramate to be a cost-effective treatment at a willingness-to-pay threshold of $100 000 to $150 000/QALY. Further research is needed to determine long-term drug efficacy and how long adolescents continue treatment.

Short-Term Effects of Recreational Cannabis Legalization on Youth Cannabis Initiation.

PURPOSE: As recreational cannabis is legalized, it is critical to know the impacts of legalization on youth cannabis use. Existing research generates conflicting results and does not shed light on channels of effects. This study investigates the impacts of legalization on youth cannabis initiation and overall cannabis use prevalence. METHODS: We used Interrupted Time Series design and data from nationally-representative repeated cross-sectional Canadian surveys spanning 16 years. The primary outcomes were cannabis initiation rates and cannabis use prevalence among youths. The secondary outcomes were self-reported age of first cannabis use, ease of cannabis access, and perception of cannabis harm among youths. RESULTS: After legalization, cannabis initiation rate among youths was 2.7 percentage points (95% confidence interval: 1.7-3.7; p < .01) or 69% higher, although there was no significant increase in the overall prevalence of cannabis use. Furthermore, there was a 4-month delay in the average age of first cannabis use among youths aged 17-18 years (95% confidence interval: 2.6-5.5 months; p < .01). The legalization was associated with greater perception of cannabis harm but also easier access to cannabis. DISCUSSION: The impacts of legalization on youth cannabis use after 1 year are mixed. Although we observed an increase in cannabis initiation among youths who had never used cannabis, there was no change in the overall prevalence of cannabis use, implying a possible offsetting increase in cannabis cessation among existing users. To achieve legalization's goal of reducing youth cannabis use, policy measures are needed to curb youth cannabis access and initiation.

Cost-effectiveness of dapagliflozin and empagliflozin for treatment of heart failure with reduced ejection fraction.

BACKGROUND: The differences in cost and efficacy between dapagliflozin and empagliflozin in combination with standard of care (SoC) raise the question of which regimen would be cost-effective in treating heart failure with reduced ejection fraction (HFrEF). This study evaluates the cost-effectiveness of dapagliflozin plus SoC (dapagliflozin-SoC) versus empagliflozin plus SoC (empagliflozin-SoC) or SoC alone for treatment of HFrEF. METHODS: We developed a Markov model to estimate the cost-effectiveness of dapagliflozin-SoC, empagliflozin-SoC, and SoC alone from the healthcare system perspective over a lifetime horizon. Data on efficacy of dapagliflozin-SoC, empagliflozin-SoC, and SoC were obtained from randomized controlled trials. Costs were measured in 2022 US dollars, and effectiveness was measured in quality-adjusted life years (QALYs). RESULTS: Among three strategies, dapagliflozin-SoC was the most cost-effective strategy and dominated empagliflozin-SoC in an extended sense. Compared with SoC alone, dapagliflozin-SoC and empagliflozin-SoC had incremental cost-effectiveness ratios (ICER) of $56,782 and $89,258 per QALY, respectively. Dapagliflozin-SoC cost more $5524 but yielded more 0.20 QALYs than empagliflozin-SoC, with the ICER of $27,861 per QALY. The cost-effectiveness of dapagliflozin-SoC, empagliflozin-SoC, and SoC alone did not depend on diabetic status. However, empagliflozin-SoC was no longer cost-effective versus SoC alone in HFrEF patients without CKD, and dapagliflozin-SoC was not cost-effective versus empagliflozin-SoC in HFrEF patients with CKD. CONCLUSION: Dapagliflozin-SoC was cost-effective versus empagliflozin-SoC or SoC alone for treatment of HFrEF.

Estimated cost-effectiveness of point-of-care testing in community pharmacies vs. self-testing and standard laboratory testing for HIV.

OBJECTIVE: Point-of-care-testing (POCT) for HIV at community pharmacies can enhance care linkage compared with self-tests and increase testing uptake relative to standard lab testing. While the higher test uptake may increase testing costs, timely diagnosis and treatment can reduce downstream HIV treatment costs and improve health outcomes. This study provides the first evidence on the cost-effectiveness of pharmacist-led POCT vs. HIV self-testing and standard lab testing. DESIGN: Dynamic transmission model. METHODS: We compared three HIV testing strategies: POCT at community pharmacies; self-testing using HIV self-test kits; and standard lab testing. Analyses were conducted from the Canadian health system perspective over a 30-year time horizon for all individuals aged 15-64 years in Canada. Costs were measured in 2021 Canadian dollars and effectiveness was captured using quality-adjusted life-years (QALYs). RESULTS: Compared with standard lab testing, POCT at community pharmacies would save $885 million in testing costs over 30 years. Though antiretroviral treatment costs would increase by $190 million with POCT as more persons living with HIV are identified and treated, these additional costs would be partly offset by their lower downstream healthcare utilization (savings of $150 million). POCT at community pharmacies would also yield over 5000 additional QALYs. Compared with HIV self-testing, POCT at community pharmacies would generate both higher costs and higher QALYs and would be cost-effective with an incremental cost-effectiveness ratio of $47 475 per QALY gained. CONCLUSIONS: Offering POCT at community pharmacies can generate substantial cost savings and improve health outcomes compared with standard lab testing. It would also be cost-effective vs. HIV self-testing.

Effects of e-cigarette use on mental health among youths: quasi-experimental evidence from Canada.

BACKGROUND AND AIMS: Existing research on mental health comorbidities of youth e-cigarette use is subject to confounding bias and reverse causality. This study aimed to measure the effects of e-cigarette use on youth mental health, using e-cigarette minimum legal age (MLA) law in Canada as a natural experiment. DESIGN: We used difference-in-differences (DD), difference-in-differences-in-differences (DDD) and two-sample instrumental variables (TSIV) methods. SETTING: Data were from nationally representative Canadian Community Health Surveys 2008-2019 and Canadian Student Tobacco Alcohol and Drugs Surveys 2008-2019. PARTICIPANTS: The study sample comprised of respondents aged 15 to 18 (in DD analysis; n = 33 858) and aged 15 to 24 (in DDD analysis; n = 78 689). MEASUREMENTS: Primary outcomes were self-reported mood disorders and anxiety disorders. Secondary outcomes were cannabis use, illicit drug use, cigarette use and strength of peer relationships at schools. FINDINGS: After the e-cigarette MLA laws, risks of mood disorders declined by 1.9 percentage points (95% CI, 0.0-3.8; P = 0.05) in the DD analysis and by 2.6 percentage points (95% CI, 0.2-5.0; P = 0.03) in the DDD analysis. For anxiety disorders, while the DD estimate was negative but imprecisely estimated, the MLA law reduced risks of anxiety disorder by 3.6 percentage points (95% CI, 0.9-6.2; P = 0.01) in the DDD analysis. Youths in provinces with MLA laws were also less likely to report cannabis use and illicit drug use and more likely to feel being part of schools. TSIV analysis indicates that youth e-cigarette use increased the likelihood of mood and anxiety disorders by 44% and 37%, respectively. CONCLUSION AND RELEVANCE: In Canada, the e-cigarette minimum legal age law appears to have reduced risks of mood and anxiety disorders, lowered substance use and improved peer relationships at schools. Combined with previous evidence of lower e-cigarette use following the minimum legal age law, our findings indicate that youth e-cigarette use increases risks of mood and anxiety disorders.