Cigarette packaging, warnings, prices, and contraband: A discrete choice experiment among smokers in Ontario, Canada.

In Canada, despite substantial decline, tobacco use remains the leading risk factor responsible for mortality and morbidity. There is overwhelming evidence that higher tobacco taxes reduce tobacco use, even if high taxes create an incentive to avoid or evade tobacco taxes. Recently, in addition to taxes, plain and standardized packaging and printing a warning on each cigarette have been lauded to reduce tobacco use. In November 2019, Canada became the country with the most comprehensive cigarette packaging regulations; and in June 2022, Canada proposed to print health warnings on individual cigarettes, the first jurisdiction to ever do so. The regulations came into force on August 1, 2023, and are being implemented through a stepwise approach. Our objective was to examine the effects of plain and standardized packaging, warning on cigarettes, price, and the availability of illicit cigarettes on intention to purchase and risk perceptions. We conducted a discrete choice experiment, and examined heterogeneity in preferences using latent class models among smokers in Ontario, Canada. We found that using latent class analyses was essential in quantifying preferences for attributes of cigarettes and cigarette packs. First, nearly half of smokers stated a preference for cheaper illicit cigarettes in a branded pack without any health warnings, regardless of the licit cigarette alternatives. For about 20% of respondents, plain packaging and especially warning on cigarette sticks decreased the probability of stating a purchasing preference for these alternatives. Third, about a third of respondents chose competing alternatives with mostly one attribute in mind, price. Lastly, none of the products and attributes seem to have significantly influenced risk perception. Our findings attest to the importance of prices and taxes, to the potential of warnings on cigarette sticks to control tobacco use, and indicate that efforts to restrict the availability of illicit cigarettes may yield substantial benefits.

Would plain packaging and health warning labels reduce smoking in the presence of informal markets? A choice experiment in Colombia.

BACKGROUND: Despite progress made by many countries on the adoption of plain tobacco packaging laws over the last years, low- and middle-income countries, with a large supply of loose cigarettes via informal vendors, remain far behind. AIM: To study the potential effectiveness of plain tobacco packaging and dissuasive cigarette sticks, via willingness-to-pay estimates, when illicit cigarette options are available. METHODS: We conducted a discrete choice experiment (DCE) in which respondents chose licit and illicit products with three attributes: packaging (standard vs. plain packaging), stick design (branded stick vs. stick with warning), and price level. The sample, collected on 12/2021, consisted of 1761 respondents from an internet panel involving smokers and nonsmokers. Conditional logit and latent class models were used to estimate the willingness-to-pay (WTP) to avoid restrictive packaging elements. RESULTS: Nonsmokers are willing to pay USD $5.63 for a pack of cigarettes to avoid plain packaging, which is higher than the actual commercial price of illicit cigarettes (USD $2.40). The WTP increases to USD $12.14 in the presence of illicit alternatives. Smokers are also willing to pay to avoid illicit options, which they also deem riskier, and the presence of such options increases the WTP to avoid plain packaging. However, nonsmokers do not perceive the illicit option as riskier. The dissuasive stick (stick with warning) does not affect perceptions of risk and plays a small role in terms of choice for both smokers and nonsmokers. CONCLUSIONS: Even in the presence of illicit tobacco alternatives, plain packaging seems to be as effective in reducing the attractiveness of tobacco products in Colombia as in other countries that have already adopted it. Given conflicting results on the case for dissuasive sticks, there is a need for more research.

Governance of mental healthcare: Fragmented accountability.

Within international healthcare systems the neglect of mental health and challenge in shifting from institutional to community care have been recurrent themes. In analysing the challenges, we focus on the case study of Canada by exploring the manner in which health law and policy evolved to inhibit community-based mental healthcare, and compare the resulting funding landscape from an international perspective. The historical institutionalist analysis draws on the literature and healthcare finance data. As a spending statute, the Canada Health Act defines the terms on which the federal government finances publicly insured provincial healthcare. Despite the goal to support physical and mental well-being by removing financial barriers to access health services, exclusion of community care offered by non-physicians (such as psychotherapy) from the terms of the Act inhibited its fulfilment. Diminished federal transfers deepened the disincentive for provinces to establish community care: mental health declined from 11 to 7 percent of provincial healthcare spending from 1979 to 2014. Governance oversight was passed to provinces whose competing demands on diminished resources limited their capacity to extend care. Accountability was found fragmented as neither government stepped-in to ensure the continuum of care, even as federal transfers were restored and evidence of cost-effectiveness grew. Although American and Canadian funding patterns are similar, other OECD countries invest between 13 and 18 percent of healthcare expenditures on mental health. Lessons from the Canadian case are the manner in which its federal structure and intergovernmental dynamics shaped health policy, and the importance of ensuring representation from a range of perspectives in policy development. Federal financial incentives were also found to profoundly impact the expansion of community-based mental healthcare. Evidence shows that public insurance for community supports would reduce healthcare expenditures and employer productivity loss, resulting in savings of $255 billion over 30 years.

Grassland songbird survival and recruitment in agricultural landscapes: implications for source-sink demography.

Population growth and decline are particularly sensitive to changes in three key life-history parameters: annual productivity, juvenile survival, and adult survival. However, for many species these parameters remain unknown. For example, although grassland songbirds are imperiled throughout North America, for this guild, only a small number of studies have assessed these parameters. From 2002 to 2006, in the agricultural landscape of the Champlain Valley of Vermont and New York, USA, we studied Savannah Sparrow (Passerculus sandwichensis) and Bobolink (Dolichonyx oryzivorus) demography on four grassland treatments: (1) early-hayed fields cut before 11 June and again in early- to mid-July; (2) middle-hayed fields cut once between 21 June and 10 July; (3) late-hayed fields cut after 1 August; and (4) rotationally grazed pastures. We assessed whether these treatments affected adult apparent survival (phi) and recruitment (f), how sensitive these parameters were to the presence of nonbreeders and local dispersal, and the populations' ability to persist in these four habitats. On average, birds using late-hayed fields had > 25% higher apparent survival than those on the more intensively managed early-hayed, middle-hayed, and grazed fields. Overall male phi was 35% higher than female phi, and Savannah Sparrow phi was 44% higher than Bobolink phi. Across all analyses and treatments, apparent survival estimates were 0.58-0.85 for male and 0.48-0.71 for female Savannah Sparrows, and 0.52-0.70 for male and 0.19-0.55 for female Bobolinks. For males of both species, potential nonbreeders decreased the precision of and lowered apparent survival estimates by 25%; female estimates showed little variation with the inclusion of nonbreeders. Inclusion of local dispersal observations increased apparent survival estimates and, in many cases, increased precision, though the effect was stronger for Savannah Sparrows than for Bobolinks, and also stronger for males than for females. High Savannah Sparrow apparent survival rates resulted in stable or near stable populations (lambda approximately 1), particularly in late-hayed and grazed fields, while low Bobolink apparent survival rates resulted in strongly declining populations (lambda < 1) in all treatments.

Grassland songbirds in a dynamic management landscape: behavioral responses and management strategies.

In recent decades, earlier and more frequent harvests of agricultural grasslands have been implicated as a major cause of population declines in grassland songbirds. From 2002 to 2005, in the Champlain Valley of Vermont and New York, USA, we studied the reproductive success of Savannah Sparrows (Passerculus sandwichensis) and Bobolinks (Dolichonyx oryzivorus) on four grassland treatments: (1) early-hayed fields cut before 11 June and again in early- to mid-July; (2) middle-hayed fields cut once between 21 June and 10 July; (3) late-hayed fields cut after 1 August; and (4) rotationally grazed pastures. Both the number of fledglings per female per year and nest success (logistic-exposure method) varied among treatments and between species. Although birds initiated nests earlier on early-hayed fields compared to others, haying caused 99% of active Savannah Sparrow and 100% of active Bobolink nests to fail. Both the initial cutting date and time between cuttings influenced renesting behavior. After haying, Savannah Sparrows generally remained on early-hayed fields and immediately renested (clutch completion 15.6 +/- 1.28 days post-haying; all values are reported as mean +/- SE), while Bobolinks abandoned the fields for at least two weeks (mean clutch completion 33 +/- 0.82 days post-haying). While female Savannah Sparrows fledged more offspring per year (1.28 +/- 0.16) than female Bobolinks (0.05 +/- 0.05), reproductive success on early-hayed fields was low. The number of fledglings per female per year was greater on middle-hayed fields (Savannah Sparrows, 3.47 +/- 0.42; Bobolinks, 2.22 +/- 0.26), and late-hayed fields (Savannah Sparrows, 3.29 +/- 0.30; Bobolinks, 2.79 +/- 0.18). Reproductive success was moderate on rotationally grazed pastures, where female Savannah Sparrows and female Bobolinks produced 2.32 +/- 0.25 and 1.79 +/- 0.33 fledgling per year, respectively. We simultaneously conducted cutting surveys throughout the Champlain Valley and found that 3-8% of hayfield habitat was cut by 1-4 June, 25-40% by 12-16 June, and 32-60% by 28 June-2 July. Thus, the majority of grassland habitat was cut during the breeding season; however, late-hayed fields served as high-quality reserves for late-nesting female Bobolinks that were displaced from previously hayed fields. For fields first cut in May, a 65-day interval between cuts could provide enough time for both species to successfully fledge young.

Fosphenytoin may cause hemodynamically unstable bradydysrhythmias.

The prodrug fosphenytoin (FOS) was recently introduced as an alternative to phenytoin (PTN) and has since become a first line therapy for status epilepticus. Unlike PTN, FOS generally has been considered to be safe from cardiac toxicity. To better characterize cardiac toxicity associated with FOS administration, we performed a review of the Food and Drug Administration's Adverse Event Reporting System databank for reports of possible FOS toxicity from 1997-2002. There were 29 applicable reports of adverse cardiac events likely related to FOS infusion, including 10 cardiac deaths. Among survivors, there were four cases of high-grade atrioventricular block, and five cases of transient sinus arrest. Our data suggest that FOS may produce more cardiac toxicity than previously thought. Clinicians should consider administering intravenous FOS in a monitored setting for selected high-risk patients.

A Semiempirical Study of the Effect of Geometry and Methyl Substituents on the Stabilities of Protonated Cyclopropylcarbinyl Ketones: Resolution of the 7-Nortricyclanone Anomaly.

A long-standing anomaly regarding the difference in stabilities of a series of protonated cyclopropylcarbinyl ketones has been resolved. The enthalpies of protonation of the ketones to the oxocarbenium ions (DeltaH(i)) were calculated from the PM3 heats of formation of the ketones and ions using isodesmic cycles. The values of DeltaH(i) correlate well with the experimentally determined values of pK(R+) for the ketones in concentrated sulfuric acid. Methyl substitution on the cyclopropyl ring uniformly stabilizes the resulting ions. Orientation of the -OH(+) to the cyclopropyl affects stability as well: a syn (periplanar) orientation lowers stability, while an anti (antiperiplanar) orientation increases it, apparently because of charge repulsion between the protonated carbonyl and the partial positive charges on the ring carbons caused by carbinyl "resonance" stabilization. Decreasing the angle about the carbonyl carbon leads to a decrease in stability for all systems tested and appears to be a major source of destabilization of the nortricycle system relative to skeletal analogs with more open carbonyl bond angles. The more stable ions have pi HOMOs, while the nortricycle and related ions have sigma HOMOs, which is another source of destabilization of the nortricycle system. For comparison, the corresponding hydrocarbon carbenium ions were examined; similar orders of stability were identified.

Reactions of Charged Substrates. 5. The Solvolysis and Sodium Azide Substitution Reactions of Benzylpyridinium Ions in Deuterium Oxide.

Second-order rate constants and activation values were measured for the reactions with NaN(3) of a series of 4-Y-substituted (Y = MeO, Me, H, Cl, and NO(2)) benzyl 3'-Z-substituted (Z = CN, CONH(2), H, F, Ac) pyridinium chlorides in deuterium oxide. 3'-Cyanopyridine substrates reacted much faster than nicotinamide and pyridine substrates; in the pyridine series the 4-Me, 4-H, and 4-Cl benzyl analogs did not react for up to 6 months at 96()() degrees C in 1.7 M NaN(3). The 3'-cyanopyridine substrates do not exhibit borderline kinetic behavior, but the nicotinamide substrates do. The Hammett plot is flat for the NaN(3) reaction of 3'-cyanopyridine substrates and increasingly V-shaped for the nicotinamide and pyridine substrates. The values of beta(LG) (four-point plot) for the NaN(3) reaction of the 4-MeO benzyl substrates is -1.45, which is usually interpreted as being a very "late" activated complex. Two-point Brønsted "plots" for the other benzyl derivatives and for two N-methylpyridinium ions give values of beta(LG) in the same range. The second-order rate constant and activation values for N-methyl-3'-cyanopyridinium iodide are within the same range as those for the benzyl substrates. For the hydrolysis reaction, the Hammett plot is linear for 3'-cyanopyridine substrates (rho(+) = -1.24) and flat for the nicotinamide substrates. The extent of hydrolysis of 0.005-0.05 M solutions of the 3'-cyanopyridinie substrates depended on the initial concentration of substrate, and hydrolysis was slowed significantly or stopped completely in the presence of exogenous 3-cyanopyridine. These results show that an equilibrium is established among the products for the 4-MeO, 4-Me, 4-H, and 4-Cl substrates; the 4-NO(2) substrate reacted too slowly to discern any difference. Data for the extent of hydrolysis were fitted by an equation derived assuming the equilibrium. Despite this limitation on a classic test of mechanism, the rates and rho values are consistent with direct displacement by solvent and not with a unimolecular process. These results, which are rationalized in terms of the Pross-Shaik model, suggest that there are no ion-dipole complex intermediates in the benzyl series and show that borderline kinetic behavior is a function of leaving group ability and is not necessarily related to a change in mechanism. A computational approach was used to evaluate anomalous beta(LG) values for the hydrolysis and nucleophilic substitution reactions of the methypyridinium ion substrates. It was found that neither the Nu-substrate bond lengths nor the difference in charge matched the beta(LG) values. The value of DeltaDeltaS() of -15 gibbs/mol between (4-methoxybenzyl)-3'-cyanopyridinium chloride and the corresponding dimethylsulfonium chloride in the NaN(3) reaction, which is the result of the solvation of the pyridine at the transition state and the lack of solvation of SMe(2), is used to argue that the source of NAD(+) glycohydrolase "catalysis" of NAD(+) bond cleavage is the result of desolvation of the leaving group upon binding.

Reactions of Charged Substrates. 6. The Methoxymethyl Carbenium Ion Problem. 1. A Semiempirical Study of the Kinetic and Thermodynamic Stabilities of Linear and Cyclic Oxo- and Thiocarbenium Ions Generated from Pyridinium and Dimethylanilinium Ions.

AM1-calculated energy profiles for dissociation of (methoxymethyl)pyridinium and dimethylanilinium ion substrates show that the methoxymethyl carbenium ion is not sufficiently stable to exist as an intermediate on the reaction coordinate for this model reaction. [(Thiomethoxy)methyl]pyridinium ion, however, has a distinct transition state because of the stability of the resulting ion-neutral complex. The complete potential energy surfaces for water displacement on the methoxymethyl substrate with either pyridine or dimethylaniline as the leaving group show distinct transition states and very flat surfaces for the ion-neutral complexes in which interaction of the carbenium ion with both leaving group and nucleophile is stabilizing. Secondary systems studied, including linear methoxy and thiomethoxy substrates, 5- and 6-membered cyclic oxo and thio substrates, and ribosyl-, xylopyranosyl-, and glucopyranosylpyridinium ions yield ion-neutral complexes with sufficient intrinsic stability to exist as intermediates. Comparison with solution data, primarily activation entropy and Brønsted coefficients, suggests that the sugar oxocarbenium ions, either as distinct, solvent-equilibrated intermediates or elements of ion-neutral complexes, are formed by unimolecular dissociation of the respective substrates in solution.

Reactions of Charged Substrates. 7. The Methoxymethyl Carbenium Ion Problem. 2. A Semiempirical Study of the Kinetic and Thermodynamic Stabilities of Linear and Cyclic Oxo- and Thiocarbenium Ions Generated from Aldehyde Hydrates, Hemiacetals, Acetals, and Methyl Ribosides and Glucosides.

Factors affecting the cleavage of the carbon-oxygen bond in linear and cyclic aldehyde hydrates, heimacetals, acetals, and methyl ribosides and glucosides have been investigated using semiempirical calculations (AM1 and PM3). (For some systems, low- and high-level ab initio energies are available for comparison with the semiempirical results. With one exception, the results obtained by the two methods show excellent agreement in relative energies and trends in reactivity.) The effects on reactivity and stability caused by substituting a sulfur for the alpha oxygen in the oxocarbenium ion were also studied. In general, systems that can have an antiperiplanar alignment of lone pairs on the leaving group and potential oxocarbenium ion oxygens undergo spontanteous cleavage. An examination of various conformers of the leaving group relative to the potential oxocarbenium oxygen shows, however, that lone pair repulsion and steric factors for MeOH as the leaving group are more important than the antiperiplanar effect for bond cleavage. All compounds in which the alpha-oxygen in the potential carbenium ion is replaced by sulfur undergo spontaneous cleavage regardless of the leaving group or structure of the compound. Energy profiles, DeltaH(), and DeltaH(R) values show that linear and cyclic thiocarbenium ions are much more stable than the corresponding oxocarbenium ions. Comparison of results for methyl ribosides and glucosides with results for corresponding pyridinium substrates suggests that both should hydrolyze through an A-1 mechanism. General-acid catalysis with hydronium as the acid was studied. With solution results, the computations suggest that substrates with either a good leaving group or stable oxocarbenium ion react with rate-limiting proton transfer from the acid to the leaving group but that substrates with both a good leaving group and stable carbenium ion react with concerted proton transfer and bond cleavage.

Reactions of Charged Substrates. 8. The Nucleophilic Substitution Reactions of (4-Methoxybenzyl)dimethylsulfonium Chloride.

Displacement reactions on the title compound (1) occur only for nucleophiles with intermediate hardness. Nucleophiles that react display a range of mechanisms. 1 reacts with the neutral nucleophile pyridine-d(5) through a mixed S(N)1/S(N)2 mechanism; salt added to control ionic strength affects the rate for the unimolecular process, but has no effect on the bimolecular rate constant. The mechanism of displacement by N(3)(-) and SO(3)(2)(-) depends on the presence or absence of exogenous salt. At constant ionic strength, the mechanism is mixed S(N)1/S(N)2 over most of the range of [Nu]. With nucleophile only present, plots of k(obsd) vs [Nu] exhibit severe breaks that are not the result of salt effects. Analysis of rate constants and product ratios suggests that at low [Nu] reaction occurs simultaneously through concerted Hughes-Ingold S(N)2 and preassociation-concerted mechanisms. At high [Nu], displacement occurs only through the preassociation-concerted mechanism. Comparison of these results with data for gas-phase dissociation of benzyl dimethylsulfoniums and with solution results for benzyl pyridiniums suggests that the intrinsic stability of the intermediate does not necessarily determine the mechanism.

Reactions of Charged Substrates. 4. The Gas-Phase Dissociation of (4-Substituted benzyl)dimethylsulfoniums and -pyridiniums.

The relative rates for the gas-phase dissociation RX(+) --> R(+) + X degrees of five (4-Y-substituted benzyl)dimethysulfoniums (Y = MeO, Me, H, Cl, and NO(2)) and 24 (4-Y-substituted benzyl)-3'-Z-pyridiniums (complete series for Z = CN, Cl, CONH(2), and H, and 4-methoxy- and 4-nitrobenzyls for Z = F and CH(3)CO) were measured using liquid secondary ion mass spectrometry. The Hammett plot (vs deltaDeltaG degrees or sigma(+)) is linear for the sulfoniums, but plots for the four pyridinium series have a drastic break between the 4-Cl and 4-NO(2) substrates. Brønsted-like plots for the pyridiniums show a strong leaving group effect only for 4-nitrobenzyls. An analysis of these linear free energy relations with supporting evidence from semiempirical computations suggests that collisionally activated pyridinium substrates dissociate by two pathways, direct dissociation and through an ion-neutral complex intermediate. Comparison of these results with results for the solution reactions of some of these compounds shows that the mechanism is different in the gas and solution phases. Sufficient experimental data are not available to assign a mechanism for dissociation to the sulfonium series, but computational results show characteristics of a direct dissociative mechanism.

The transition from good to poor health: an econometric study of the older population.

This is a study of the influence of socioeconomic factors on the state of health of older Canadians. Three years of panel data from the Survey of Labour and Income Dynamics are used to model the transition probabilities between good and poor health. Care is taken to avoid the problem of endogeneity of income in modelling its effects, and to adjust reported income to free it from its strong association with age at the time of the survey. Of particular note are the significant effects found for income, in spite of universal public health care coverage. Significant effects are found also for age, education, and other variables.

Healthy aging at older ages: are income and education important?

Being higher on the socio-economic scale is correlated with being in better health, but is there is a causal relationship? Using 3 years of longitudinal data for individuals aged 50 and older from the Canadian Survey of Labour and Income Dynamics, we study the health transitions for those who were in good health in the first year, focusing especially on income and education. The initial good health restriction removes from the sample those whose incomes may have been affected by a previous history of poor health, thus avoiding a well-known problem of econometric endogeneity. We then ask, for those in good health, whether later transitions in health status are related to socio-economic status. We find that they are-that changes in health status over the subsequent 2 years are related, in particular, to income and education.