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1.
Value Health ; 26(7): 1107-1129, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36842717

RESUMEN

OBJECTIVES: In Canada, public insurance for physician and hospital services, without cost-sharing, is provided to all residents. Outpatient prescription drug coverage, however, is provided through a patchwork system of public and private plans, often with substantial cost-sharing, which leaves many underinsured or uninsured. METHODS: We conducted a systematic review to examine the association of drug insurance and cost-sharing with drug use, health services use, and health in Canada. We searched 4 electronic databases, 2 grey literature databases, 5 specialty journals, and 2 working paper repositories. At least 2 reviewers independently screened articles for inclusion, extracted characteristics, and assessed risk of bias. RESULTS: The expansion of drug insurance was associated with increases in drug use, individuals who reported drug insurance generally reported higher drug use, and increases in and higher levels of drug cost-sharing were associated with lower drug use. Although a number of studies found statistically significant associations between drug insurance or cost-sharing and health services use, the magnitudes of these associations were generally fairly small. Among 5 studies that examined the association of drug insurance and cost-sharing with health outcomes, 1 found a statistically significant and clinically meaningful association. We did not find that socioeconomic status or sex were effect modifiers; there was some evidence that health modified the association between drug insurance and cost-sharing and drug use. CONCLUSIONS: Increased cost-sharing is likely to reduce drug use. Universal pharmacare without cost-sharing may reduce inequities because it would likely increase drug use among lower-income populations relative to higher-income populations.


Asunto(s)
Medicamentos bajo Prescripción , Humanos , Canadá , Seguro de Servicios Farmacéuticos , Seguro de Costos Compartidos , Servicios de Salud , Seguro de Salud
2.
J Med Chem ; 67(11): 9173-9193, 2024 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-38810170

RESUMEN

While in the process of designing more effective synthetic opioid rescue agents, we serendipitously identified a new chemotype of potent synthetic opioid. Here, we report that conformational constraint of a piperazine ring converts a mu opioid receptor (MOR) antagonist into a potent MOR agonist. The prototype of the series, which we have termed atoxifent (2), possesses potent in vitro agonist activity. In mice, atoxifent displayed long-lasting antinociception that was reversible with naltrexone. Repeated dosing of atoxifent produced antinociceptive tolerance and a level of withdrawal like that of fentanyl. In rats, while atoxifent produced complete loss of locomotor activity like fentanyl, it failed to produce deep respiratory depression associated with fentanyl-induced lethality. Assessment of brain biodistribution demonstrated ample distribution of atoxifent into the brain with a Tmax of approximately 0.25 h. These results indicate enhanced safety for atoxifent-like molecules compared to fentanyl.


Asunto(s)
Analgésicos Opioides , Fentanilo , Receptores Opioides mu , Insuficiencia Respiratoria , Animales , Ratones , Receptores Opioides mu/agonistas , Receptores Opioides mu/metabolismo , Insuficiencia Respiratoria/inducido químicamente , Insuficiencia Respiratoria/tratamiento farmacológico , Analgésicos Opioides/farmacología , Analgésicos Opioides/síntesis química , Analgésicos Opioides/química , Ratas , Masculino , Fentanilo/farmacología , Fentanilo/síntesis química , Fentanilo/química , Relación Estructura-Actividad , Piperazinas/farmacología , Piperazinas/química , Piperazinas/síntesis química , Piperazinas/uso terapéutico , Piperazinas/farmacocinética , Humanos , Ratas Sprague-Dawley , Distribución Tisular , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Naltrexona/farmacología , Naltrexona/análogos & derivados , Naltrexona/síntesis química , Naltrexona/química , Naltrexona/uso terapéutico
3.
PLOS Glob Public Health ; 3(9): e0002342, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37756265

RESUMEN

There is indisputable evidence that increases in taxes that raise tobacco prices reduce tobacco use. Consumption taxes on manufactured tobacco products, however, can be regressive in socioeconomic status (e.g., when the ratio of tax paid to income is lower for higher-income groups than for lower-income groups). Nevertheless, if the poor or less educated are more price responsive, a change in tobacco tax may be progressive in socioeconomic status. Existing reviews clearly indicate that populations with lower income or education are more responsive to tobacco tax and price changes than higher-income and more educated populations in high-income countries. Research pertaining to low- and middle-income countries was, however, limited and inconclusive. We conducted a review of quantitative studies that examined if socioeconomic status modified the association between prices and taxes and tobacco use in low- and middle-income countries. We searched two electronic databases, two search engines, and two working paper repositories. At least two reviewers independently screened articles for inclusion, extracted detailed characteristics, and assessed the risk of bias of each included study. Thirty-two studies met our inclusion criteria. Overall, we found that the evidence in low- and middle-income countries was too limited and methodologically weak to make any conclusive statements. Our review highlights a number of data and methodological limitations in existing studies. The most important limitation was the lack of formal assessment of socioeconomic differences in price responsiveness. Only seven of 32 studies assessed statistically whether own-price effects were modified by socioeconomic status. Many modelling studies have examined the distributional effect of a tax increase on tobacco use, while assuming a strong own-price elasticity gradient in income. The poor were generally assumed to be more responsive to price by a factor of two to five, relative to the wealthy. Although there are theoretical reasons to expect poorer individuals to be more responsive to monetary prices than wealthy ones in low- and middle-income countries, our review provides little empirical support.

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