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AbstractAimsTo examine how standard analytical approaches to model mortality outcomes of alcohol use compare to the true results using the impact of the March 2017 alcohol taxation increase in Lithuania on all-cause mortality as an example.MethodsFour methodologies were used: two direct methodologies: (a) interrupted time-series on mortality and (b) comparing predictions based on time-series modeling with the real number of deaths for the year following the implementation of the tax increase; and two indirect methodologies: (c) combining a regression-based estimate for the impact of taxation on alcohol consumption with attributable-fraction methodology and (d) using price elasticities from meta-analyses to estimate the impact on alcohol consumption before applying attributable-fraction methodology.Results and ConclusionsWhile all methodologies estimated reductions in all-cause mortality, especially for men, there was substantial variability in the level of mortality reductions predicted. The indirect methodologies had lower predictions as the meta-analyses on elasticities and risk relations seem to underestimate the true values for Lithuania. Directly estimated effects of taxation based on the actual mortalities seem to best represent the true reductions in alcohol-attributable mortality. A significant increase in alcohol excise taxation had a marked impact on all-cause mortality in Lithuania.

Alcohol and nicotine (in the form of tobacco) are often taken together, with increased negative health consequences. Co-use may modify intake of one or both of the drugs, or the effects of drugs used to treat nicotine or alcohol addiction. Varenicline is commonly prescribed as an aid to enhance quitting smoking. More recently it has been shown to reduce alcohol intake in humans and laboratory animals. There is little work investigating the role of co-exposure to alcohol and nicotine in the effects of varenicline. In pilot clinical studies, it has been reported that smoking enhances varenicline's effectiveness as a treatment for alcohol misuse, but this relationship has not been systematically investigated. To help resolve this, we examined if the effects of varenicline on alcohol and nicotine self-administration (SA) in rats are modified when the two drugs are taken together. Rats were trained on alcohol SA, and some were implanted with i.v. catheters for nicotine SA. Groups of animals then lever pressed for alcohol or nicotine alone, and another group lever pressed for alcohol and nicotine, using a two lever choice procedure. Varenicline did not affect alcohol SA. Varenicline reduced nicotine SA modestly. Access to both alcohol and nicotine reduced self-administration of either drug, but did not change the effects of varenicline. We found that in rats with a history of alcohol SA, varenicline reduced reinstatement of extinguished alcohol seeking induced by exposure to an alcohol prime combined with cues previously associated with alcohol.

Most cost of illness studies are based on models where information on exposure is combined with risk information from meta-analyses, and the resulting attributable fractions are applied to the number of cases.This study presents data on alcohol and tobacco use for 2011 and 2012 obtained from a routine medical practice in Catalonia of 606 947 patients, 18 years of age and older, as compared with health care costs for 2013 (all costs from the public health care system: primary health care visits, hospital admissions, laboratory and medical tests, outpatient visits to specialists, emergency department visits and pharmacy expenses). Quasi-Poisson regressions were used to assess the association between alcohol consumption and smoking status and health care costs (adjusted for age and socio-economic status).Resulting health care costs per person per year amounted to 1290 Euros in 2013, and were 20.1% higher for men than for women. Sex, alcohol consumption, tobacco use and socio-economic status were all associated with health care costs. In particular, alcohol consumption had a positive dose-response association with health care costs. Similarly, both smokers and former smokers had higher health care costs than did people who never smoked.Alcohol and tobacco use had modest and large impacts respectively on health care costs, confirming the results of previous ecological modelling analyses. Reductions of alcohol consumption and smoking through public policies and via early identification and brief interventions would likely be associated with reductions in health care costs.

The role of the dopamine D1 receptor subtype in alcohol-seeking behaviors was studied in mice genetically deficient in dopamine D1 receptors (D1 -/-). In two-tube free choice limited (1-5 h) and continuous (24 h) access paradigms, mice were exposed to water and increasing concentrations of ethanol (3%, 6% and 12% w/v). Voluntary ethanol consumption and preference over water were markedly reduced in D1 -/- mice as compared to heterozygous (D1 +/-) and wild-type (D1 +/+) controls, whereas overall fluid consumption was comparable. When offered a single drinking tube containing alcohol as their only source of fluid for 24 h, D1 -/- mice continued to drink significantly less alcohol than D1 +/+ and D1 +/- mice. Dopamine D2 receptor blockade with sulpiride caused a small but significant reduction in alcohol intake and preference in D1 +/+ mice and attenuated residual alcohol drinking in D1 -/- mice. Dopamine D1 receptor blockade with SCH-23390 very effectively reduced alcohol intake in D1 +/+ and D1 +/- mice to the level seen in untreated D1 -/- mice. These findings suggest involvement of both dopamine D1 and D2 receptor mechanisms in alcohol-seeking behavior in mice; however, these implicate D1 receptors as having a more important role in the motivation for alcohol consumption.

The choroid plays an important role in various ocular pathologies and retinal blood supply. There is a knowledge gap on how the choroid is affected by systemic and topical medications. Systemic medications that affect microvasculature elsewhere in the body can also affect the microvasculature of the choroid. This review summarizes current knowledge on associations between systemic and topical medications and changes in choroidal thickness (CT). This review included 71 studies on mydriatics/cycloplegics, intraocular pressure (IOP)‐lowering therapies, antihypertensives, adrenergic antagonists, statins, corticosteroids, hydroxychloroquine, isotretinoin, hormonal contraceptives, phosphodiesterase inhibitors, antipsychotics, antineoplastic agents, ethanol, caffeine and nicotine. IOP‐lowering therapies, atropine eye drops, and systemic administration of β blockers and ethanol are associated with a significant increase in CT. Cyclopentolate and phenylephrine are associated with a CT reduction. Systemic medications that decrease CT include caffeine and nicotine. Tropicamide, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, statins, corticosteroids, hydroxychloroquine and hormonal contraceptives have mixed findings. CT increase associated with IOP‐lowering therapies is possibly achieved by enhancing aqueous humour flow to the choroid thus elevating choroidal blood flow and thickness. CT changes appear to be independent from systemic blood pressure changes, suggesting that a significant association with an antihypertensive could be due to an idiosyncratic drug property. Statins and candesartan decrease macrophage accumulation and intercellular adhesion molecule 1 expression in the choroid. The choroid and its response to various disease processes and systemic medication can be further investigated to improve patient care, particularly in patients with choroid and retina pathologies.

The evolving epidemiological literature, including improved methodology for assessing causality in observational studies, is raising doubts about whether moderate alcohol consumption has a protective effect on health.