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Despite advances in understanding the genetic abnormalities in myeloproliferative neoplasms (MPN) and the development of JAK2 inhibitors, there is an urgent need to devise new treatment strategies, particularly for patients with triple-negative (TN) myelofibrosis (MF) who lack mutations in the JAK2 kinase pathway and have very poor clinical outcomes. Here we report that MYC copy number gain and increased MYC expression frequently occur in TN-MF and that MYC-directed activation of S100A9, an alarmin protein that plays pivotal roles in inflammation and innate immunity, is necessary and sufficient to drive development and progression of MF. Notably, the MYC-S100A9 circuit provokes a complex network of inflammatory signaling that involves numerous hematopoietic cell types in the bone marrow microenvironment. Accordingly, genetic ablation of S100A9 or treatment with small molecules targeting the MYC-S100A9 pathway effectively ameliorates MF phenotypes, highlighting the MYC-alarmin axis as a novel therapeutic vulnerability for this subgroup of MPNs. Significance: This study establishes that MYC expression is increased in TN-MPNs via trisomy 8, that a MYC-S100A9 circuit manifest in these cases is sufficient to provoke myelofibrosis and inflammation in diverse hematopoietic cell types in the BM niche, and that the MYC-S100A9 circuit is targetable in TN-MPNs.
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Calgranulina B , Cromossomos Humanos Par 8 , Transtornos Mieloproliferativos , Proteínas Proto-Oncogênicas c-myc , Trissomia , Cromossomos Humanos Par 8/genética , Humanos , Trissomia/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Calgranulina B/genética , Calgranulina B/metabolismo , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/metabolismo , Transtornos Mieloproliferativos/patologia , Animais , Camundongos , Mielofibrose Primária/genética , Mielofibrose Primária/patologia , Mielofibrose Primária/metabolismo , Transdução de Sinais/genéticaRESUMO
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.
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Cannabis , Humanos , Bebidas Alcoólicas , Etanol , Canadá/epidemiologia , Cerveja , Legislação de MedicamentosRESUMO
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.
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Doença de Alzheimer , Anticorpos Monoclonais Humanizados , Disfunção Cognitiva , Demência , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Doença de Alzheimer/tratamento farmacológico , Análise Custo-Benefício , Apolipoproteína E4/genética , Demência/diagnóstico , Disfunção Cognitiva/genética , Disfunção Cognitiva/diagnósticoRESUMO
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 100â¯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 100â¯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.
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Uso da Maconha , Maconha Medicinal , Overdose de Opiáceos , Humanos , Analgésicos Opioides/efeitos adversos , Legislação de Medicamentos , Maconha Medicinal/efeitos adversos , Maconha Medicinal/uso terapêutico , Overdose de Opiáceos/mortalidade , Prescrições , Uso da Maconha/efeitos adversosRESUMO
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 100â¯000 population; 95% CI, 1322.1-3917.0 per 100â¯000 population; P < .001) and claimants (176.4 per 100â¯000 population; 95% CI, 33.5-319.4 per 100â¯000 population; P = .02). There was no significant change in prescribers (15.7 per 100â¯000 population; 95% CI, -0.2 to 31.6 per 100â¯000 population; P = .053). However, the opioid-related poisoning hospitalization rate increased by 3.2 per 100â¯000 population (95% CI, 0.9-5.6 per 100â¯000 population; P = .01) after policy implementation. There were no statistically significant changes in deaths from apparent opioid toxicity (1.6 per 100â¯000 population; 95% CI, -1.3 to 4.5 per 100â¯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.
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Overdose de Drogas , Transtornos Relacionados ao Uso de Opioides , Humanos , Analgésicos Opioides/uso terapêutico , Colúmbia Britânica/epidemiologia , Estudos de Coortes , Padrões de Prática Médica , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Overdose de Drogas/epidemiologia , Overdose de Drogas/prevenção & controleRESUMO
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.
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Cannabis , Maconha Medicinal , Humanos , Maconha Medicinal/efeitos adversos , Cannabis/efeitos adversos , Terra Nova e Labrador , Alberta , Agonistas de Receptores de CanabinoidesRESUMO
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 $93â¯620 per QALY relative to no treatment in this simulated cohort of 10â¯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 ($1â¯079â¯480/QALY) that exceeded the commonly used willingness-to-pay threshold of $100â¯000 to $150â¯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 $100â¯000 to $150â¯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 $100â¯000 to $150â¯000/QALY. Further research is needed to determine long-term drug efficacy and how long adolescents continue treatment.
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Fármacos Antiobesidade , Obesidade Mórbida , Humanos , Feminino , Adolescente , Criança , Masculino , Fármacos Antiobesidade/uso terapêutico , Obesidade Mórbida/tratamento farmacológico , Obesidade Mórbida/cirurgia , Análise Custo-Benefício , Orlistate/uso terapêutico , Topiramato/uso terapêutico , Liraglutida/uso terapêutico , Obesidade/tratamento farmacológico , Fentermina/uso terapêuticoRESUMO
Background The coronavirus disease 2019 (COVID-19) pandemic caused changes in surgical practice. For acute appendicitis (AA), measures to control the pandemic might hinder patients from seeking medical care timely, resulting in increasing severity, postoperative complications, and mortality. This study aimed to investigate whether the COVID-19 pandemic had a negative impact on the severity and postoperative outcomes of patients with AA. Methodology We retrospectively reviewed medical records of AA patients treated operatively at Nhan Dan Gia Dinh Hospital hospital from June 1st to September 30th in three consecutive years: pre-pandemic (2019)/Group 1, minor waves (2020)/Group 2, and major wave (2021)/Group 3 (2021). Data were collected focusing on the duration of symptoms, severity of AA, time from admission to operation, postoperative complications, and mortality. Results There were 1,055 patients, including 452 patients in Group 1, 409 in Group 2, and 194 in Group 3. The overall number of patients decreased mainly in non-complicated AA. The percentages of hospital admission after 24 hours gradually increased (20.8%, 27.9%, and 43.8%, p < 0.05). The percentages of complicated AA in Group 2 and Group 3 were statistically higher than in Group 1 (39% and 55% vs. 31%, p < 0.05). Waiting time for operation increased to five hours during the major wave. Laparoscopic appendectomy was performed in 98-99% of AA patients during the pandemic, with an early postoperative complication rate of 5-9% and a mortality rate of 0.2-1%. Conclusions Although the percentages of hospital admission after 24 hours and complicated AA increased, laparoscopic appendectomy was still feasible and effective and should be maintained as the standard management for AA during the COVID-19 pandemic.
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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.
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Canagliflozina/uso terapêutico , Análise Custo-Benefício , Quimioterapia Combinada , Canadá/epidemiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Anos de Vida Ajustados por Qualidade de VidaRESUMO
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 15-64âyears 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 30âyears. 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.
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Infecções por HIV , Farmácias , Humanos , Infecções por HIV/diagnóstico , Análise Custo-Benefício , Autoteste , Canadá , Testes Imediatos , Anos de Vida Ajustados por Qualidade de VidaRESUMO
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.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Simportadores , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Glucose/uso terapêutico , Hipoglicemiantes/efeitos adversos , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Metanálise em Rede , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/induzido quimicamente , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Simportadores/uso terapêuticoRESUMO
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.
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Insuficiência Cardíaca , Insuficiência Renal Crônica , Humanos , Compostos Benzidrílicos , Análise Custo-Benefício , Anos de Vida Ajustados por Qualidade de Vida , Volume SistólicoRESUMO
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.
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Cannabis , Fumar Maconha , Adolescente , Humanos , Fumar Maconha/epidemiologia , Estudos Transversais , Canadá/epidemiologia , Legislação de MedicamentosRESUMO
PURPOSE: Direct oral anticoagulants (DOACs) have a better safety and efficacy profile than warfarin and are currently recommended for stroke prevention in non-valvular atrial fibrillation (AF) and treatment of venous thromboembolism (VTE). Given that DOACs do not require regular laboratory monitoring compared to warfarin, patients' interactions with the health care system is reduced. Adequate adherence to DOACs is important and reported adherence to anticoagulation is unclear in clinical practice. This study aims to assess self-reported adherence to oral anticoagulants in a specialized Adult Outpatient Thrombosis Service (TS).  METHODS: This cross-sectional study included patients aged ≥ 18 years who were prescribed an oral anticoagulant and had attended at least one appointment with an Adult Outpatient Thrombosis Service (TS) between October 10, 2017, and May 31, 2019. Adherence to oral anticoagulant therapy was assessed using the 12-item validated Adherence to Refills and Medications Scale (ARMS) score. Logistic regression analyses were used to evaluate association between patient characteristics and medication adherence. Adherence rates in DOACs and warfarin were compared. RESULTS: Three hundred and ninety-nine patients completed and returned the survey. Of the 399 who completed the survey, 74% were prescribed DOACs and 26% received warfarin. Most of the patients (89.3%) were ≥ 50 years of age and half (57.3%) were male. About two-thirds (67%) had at least post-secondary education. The duration of anticoagulation use differed between patients on DOAC and warfarin; a greater proportion of those who had used anticoagulants for less than 1 year was on DOACs compared to warfarin (20.9% vs 4.9%, p = 0.001). For patients who had been on anticoagulation for > 5 years, the proportion of warfarin patients was greater than DOAC (57.8% vs 20.5%, p = 0.001). Self-reported adherence to oral anticoagulant therapy using the 12-item ARMS scale for warfarin and DOACs were 87.3% and 90.9%, respectively. Among the warfarin users, patient satisfaction with TS was associated with medication adherence (OR = 0.22; 95% CI: 0.05-0.89). CONCLUSIONS: Self-reported medication adherence was similar between warfarin and DOACs. Since suboptimal adherence is associated with poor clinical outcomes and increased costs, various stakeholders should emphasize the importance of medication adherence to oral anticoagulants at each patient encounter.
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Fibrilação Atrial , Acidente Vascular Cerebral , Trombose , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Varfarina/uso terapêutico , Estudos Transversais , Autorrelato , Administração Oral , Canadá , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Acidente Vascular Cerebral/prevenção & controleRESUMO
OBJECTIVES: Family caregivers play a fundamental role in the care of the older blunt trauma patient. We aim to identify risk factors for negative and positive experiences of caregiving among family caregivers. DESIGN: Prospective, nationwide, multi-center cohort study. SETTING AND PARTICIPANTS: 110 family caregivers of Singaporeans aged≥55 admitted for unintentional blunt trauma with an Injury Severity Score (ISS) or New Injury Severity Score (NISS)≥10 were assessed for caregiving-related negative (disturbed schedule and poor health, lack of family support, lack of finances) and positive (esteem) experiences using the modified-Caregiver Reaction Assessment (m-CRA) three months post-injury. METHODS: The association between caregiver and patient factors, and the four m-CRA domains were evaluated via linear regression. RESULTS: Caregivers of retired patients and caregivers of functionally dependent patients (post-injury Barthel score <80) reported a worse experience in terms of disturbed schedule and poor health (ß-coefficient 0.42 [95% Confidence Interval 0.10, 0.75], p = .01; 0.77 [0.33, 1.21], p = .001), while male caregivers and caregivers who had more people in the household reported a better experience (-0.39 [-0.73, -0.06], p = .02; -0.16 [-0.25, -0.07], p = .001). Caregivers of male patients, retired patients, and patients living in lower socioeconomic housing were more likely to experience lack of family support (0.28, [0.03, -0.53], p = .03; 0.26, [0.01, 0.52], p = .05; 0.34, [0.05, -0.66], p = .02). In the context of lack of finances, caregivers of male patients and caregivers of functionally dependent patients reported higher financial strain (0.74 [0.31, 1.17], p = .001; 0.84 [0.26, 1.43], p = .01). Finally, caregivers of male patients reported higher caregiver esteem (0.36 [0.15, 0.57], p = .001). CONCLUSIONS AND IMPLICATIONS: Negative and positive experiences of caregiving among caregivers of older blunt trauma patients are associated with pre-injury disability and certain patient and caregiver demographics. These factors should be considered when planning the post-discharge support of older blunt trauma patients.
Assuntos
Cuidadores , Ferimentos não Penetrantes , Assistência ao Convalescente , Estudos de Coortes , Família , Humanos , Masculino , Alta do Paciente , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
Importance: In January 2020, Quebec raised the minimum legal age (MLA) for cannabis from 18 to 21 years. Evidence is needed to inform the ongoing debate on this policy. Although proponents believe that a higher MLA will protect youths from the harms of cannabis use, critics argue that it will push them back to the illegal market. Objective: To investigate changes in youth cannabis use after an increase in MLA for cannabis in Quebec. Design, Setting, and Participants: This cross-sectional study with difference-in-differences analysis compared changes in cannabis use among youths aged 15 to 20 years in Quebec vs all other Canadian provinces before and after Quebec's increase in MLA. All estimates in descriptive and regression analyses were weighted. Nationally representative data from the National Cannabis Surveys 2018-2020 were used. Intervention: Increase in MLA for cannabis in Quebec implemented in January 2020. Main Outcomes and Measures: Past-3-month cannabis use. Results: The study sample included 1005 respondents (mean [SD] age, 17.5 [1.7] years; 50.2% [SD, 50.0%] male). After policy implementation, the increase in past-3-month cannabis use among youths aged 18 to 20 was 16.4 percentage points (95% CI, -27.3 to -5.5 percentage points; P = .01), or 51%, lower in Quebec than in other provinces. Meanwhile, no significant change in cannabis use among youths aged 15 to 17 years was found. The results were robust to several checks, including accounting for possible confounding effects of the COVID-19 pandemic on cannabis use. Conclusions and Relevance: In this study, an increase in the MLA from 18 to 21 years in Quebec was associated with a significantly lower increase in cannabis use among youths aged 18 to 20 years but no change in cannabis use among those aged 15 to 17 years. These findings can help to alleviate concerns that youths would switch to illegal markets in response to a higher MLA.
Assuntos
COVID-19 , Cannabis , Adolescente , Canadá/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pandemias , Quebeque/epidemiologiaRESUMO
BACKGROUND: In October 2017 we opened a multidisciplinary Adult Outpatient Thrombosis Service (Thrombosis Service) in a regional health authority servicing over 300 000 people. The Thrombosis Service is a comprehensive thrombosis and anticoagulation management program with unique, interrelated clinics providing a broad spectrum of care for this patient group. Evaluation of patient satisfaction with this new model of patient care is an important quality measurement. METHODS: We conducted a cross-sectional survey of patients who attended the Thrombosis Service between October 2017 and May 2019. We measured patient satisfaction with the seven-item Short Assessment of Patient Satisfaction (SAPS) which uses a 5 point scale (0-4) for responses. The continuous score range for SAPS is 0 to 28. Categorical responses for SAPS are defined as 0-10 very dissatisfied, 11-18 dissatisfied, 19-26 satisfied, and 27-28 very satisfied. We used linear regression analysis to examine the associations between patients' characteristics and their satisfaction with the Thrombosis Service. RESULTS: Of the 1058 surveys distributed, 563 were returned. The mean score for the SAPS was 22.1 (SD 4.1, range 8 to 28). For the categorical response, 85% were satisfied or very satisfied with the Thrombosis Service. The multivariate analysis showed patients with post-secondary education were more satisfied with the Thrombosis Service (ß-coefficient 1.6153, p = 0.024), and patients taking warfarin were less likely to be satisfied with the Thrombosis Service (ß-coefficient -1.5832, p = 0.0390). CONCLUSIONS: The majority of survey participants (85%) who attended an appointment in one of the Thrombosis Service clinics were satisfied or very satisfied with the care they received. This information may benefit other centres who are interested in developing a program to manage thrombosis and anticoagulation.
Assuntos
Satisfação do Paciente , Trombose , Adulto , Anticoagulantes/uso terapêutico , Estudos Transversais , Humanos , Inquéritos e Questionários , Trombose/terapiaRESUMO
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.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Drogas Ilícitas , Transtornos Relacionados ao Uso de Substâncias , Vaping , Adolescente , Canadá/epidemiologia , Estudos Transversais , Humanos , Saúde Mental , Vaping/epidemiologiaRESUMO
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.