To smoke or not to smoke: Does delay discounting affect the proximal choice to smoke?

Background: Delay discounting rate shows robust predictive validity for tobacco use behaviors and is a new therapeutic target in the treatment of tobacco use. Identifying factors that influence relations between delay discounting and the choice to smoke cigarettes is key to the development of effective interventions that target delay discounting to reduce cigarette consumption. Objective: To examine relations between delay discounting, motivational factors, self-efficacy, nicotine dependence level, and the proximal choice to smoke in the context of other commonly rewarding activity choices. Methods: In this cross-sectional design, daily smokers (n?=?480) from Amazon Mechanical Turk completed a questionnaire that assessed delay discounting rate; motivation, intention, and self-efficacy to quit smoking; nicotine dependence level, and the preference for immediately engaging in multiple commonly rewarding activities. We hypothesized that 1) greater motivation to quit would be associated with lower priority given to smoking; 2) the relation between delay discounting and the priority given to smoking would be mediated by motivation, self-efficacy, and nicotine dependence level. Results: Greater motivation to quit was significantly associated with a lower priority given to smoking. The relation between delay discounting and the priority given to smoking was marginally mediated by nicotine dependence level (p > .057). Conclusions: Motivation to quit influences decision-making by impacting the prioritization of choices. Nicotine dependence is likely to mediate the relation between delay discounting and the choice to smoke. Interventions that target delay discounting to reduce cigarette consumption or prevent relapse need to account for motivation to quit and nicotine dependence level.     

Euphoriant effects of nicotine in smokers: fact or artifact?

Rationale The claim that nicotine in cigarettes is euphoriant to smokers is largely based on two studies (Pomerleau and Pomerleau, Psychopharmacology, 108:460–465, 1992; Tobacco Control, 3:374, 1994) in which smokers were instructed to respond to sensations of rush, buzz, or high while smoking low-nicotine or regular cigarettes. However, the assumption that these sensations are pleasurable was not tested and may have biased the results. Objectives The aim of this study was to re-examine the claim that smoked nicotine is euphoriant to smokers. Methods Study 1 surveyed the frequency and pleasantness of the smoking-related sensations of rush, buzz, and high in a sample of smokers. Study 2 replicated Pomerleau and Pomerleau (Psychopharmacology, 108:460–465, 1992) with two sets of instruction. One set, as in the original study, defined these sensations as pleasurable, whereas the other defined them as unpleasant. Results Study 1 found that whereas rush and high were perceived as pleasant, buzz was unpleasant to most smokers. Study 2 found that under both sets of instructions, smokers reported more sensations when smoking the regular, as compared to the low-nicotine cigarette. Additionally, the sensations of rush, buzz, and high were rated as more pleasant under the pleasant instructions as compared to the unpleasant instructions. Finally, in the pleasant instructions condition, many participants reported having pressed the button to indicate a pleasurable sensation despite having actually experienced that sensation as unpleasant. Conclusions Our results suggest that the findings of Pomerleau and Pomerleau (Psychopharmacology, 108:460–465, 1992; Tobacco Control, 3:374, 1994) may have been biased by the experimental instructions and cannot be taken as evidence that smoked nicotine is euphoriant to smokers.     

Lithium and cognitive enhancement: leave it or take it?

Rationale

Lithium is established as an effective treatment of acute mania, bipolar and unipolar depression and as prophylaxis against bipolar disorder. Accumulating evidence is also delineating a neuroprotective and neurotrophic role for lithium. However, its primary effects on cognitive functioning remain ambiguous.

Objectives

The aim of this paper is to review and combine the relevant translational studies, focusing on the putative cognitive enhancement properties of lithium, specifically on learning, memory, and attention.

Discussion

These properties are also discussed in reference to research demonstrating a protective action of lithium against cognitive deficits induced by various challenges to the nervous system, such as stress, trauma, neurodegenerative disorders, and psychiatric disorders.

Conclusions

It is suggested on the basis of the evidence that the cognitive effects of lithium are best expressed and should, therefore, be sought under conditions of functional or biological challenge to the nervous system.     

To sequence or not to sequence?

There is now incontrovertible evidence that a combination of two nucleoside analogues is superior to AZT monotherapy for the treatment of HIV infection. There is also evidence that a range of antiretroviral combinations can produce profound drops in plasma HIV viral load, often below the detectable limits of the assay. A lower rate of viral replication is associated with delays in the selection of viral mutants resistant to drugs; the principal reason for therapeutic failure. These highly effective combinations are likely to delay clinical events and considerably improve the prognosis in HIV-infected individuals. Using mathematical modelling techniques to assess the half-life of plasma virus infectious cells and proviral DNA, one group has gone so far as to suggest it may be possible to stop therapy after several years, as the virus will have been eliminated. More sanguine investigators, however, believe that this is unlikely, as some infected cellular compartments may have long half-lives and the virus may persist, or even continue to replicate slowly, in sanctuary sites, such as the CNS and genital tract, poorly penetrated by drugs. Thus, some virologists and clinicians believe that it is crucially important to give initial therapy with the strongest possible combination of drugs to achieve an 'undetectable' plasma viral load and that, providing compliance is good, this will lead to a prolonged therapeutic effect. In these circumstances no sequencing issues arise. Others, however, continue to believe that, in due course, the virus is likely to evade drug pressure. In these circumstances, consideration of a sequence of drugs, to avoid initial and subsequent therapy from squandering future therapy options through, principally, cross-resistance, becomes an important issue. None of the issues discussed in this review has been tested by controlled clinical trials but they generate hypotheses requiring urgent evaluation.     

Akathisia with Erythromycin: Induced or precipitated?

Objective: A 28-year-old male diagnosed with schizophrenia, maintaining well on Olanzapine, developed akathisia soon after addition of Erythromycin for Pityriasis Rosea. This prompted us to evaluate the relationship of Erythromycin and akathisia. Method: We report the case and the literature focusing on akathisia as a possible adverse event of Erythromycin. Results: Akathisia resolved after Erythromycin was stopped following 5 days of treatment. Akathisia was possibly induced or precipitated with use of Erythromycin. Possible etiological reasons of this clinically significant association are discussed. Conclusion: Erythromycin, by itself, may induce akathisia or precipitate akathisia in individuals by interfering with metabolism of other culprit drugs.     

Hardcore smokers: What do we know?

Aims

The existence of smokers who are resistant to smoking cessation treatment has long been noted in the literature. There has been ongoing debate as to whether the proportion of these smokers is increasing as smoking prevalence rates stagnate. Studies define hardcore smokers inconsistently and within the context of specific illnesses, addiction, population, and/or theoretical paradigms. This review examines the existing literature related to hardcore smokers to develop a better understanding of what is known and not known about this group to guide smoking cessation treatment.

Methods

PubMed MESH search and review of research publications from 1998 to 2012 (N = 61).

Results

Inconsistent definitions of hardcore smoking make it difficult to estimate prevalence rates and to identify specific characteristics of persistent smokers. Generally, persistent smokers have higher levels of nicotine dependence, are disproportionately from lower socioeconomic groups, start smoking at an earlier age, and are more likely to have a psychological co-morbidity.

Discussion

Defining some smokers as hardcore is limiting. Targeted and tailored interventions for smoking cessation for persistent smoking have demonstrated effectiveness in a small number of studies. Treatment access barriers need to be addressed to improve the reach and effectiveness of cessation with persistent smokers. Efforts to limit early age initiation of tobacco use are a critical element in averting persistent smoking.     

NSAIDs: take with food or after fasting?

Objective Published and regulatory advice is to take NSAIDs with fluids and/or food irrespective whether NSAIDs are taken over the counter or long‐term. The basis for this recommendation is not clear and we sought to establish the reasons for it through a search of published literature and personal files. Results Results from experimental animals show that fasting increases the gastric side effects of NSAIDs while food increases small bowel damage, but this has not been tested in humans. The possible effects of food in modifying the gastric damage caused by NSAIDs are complex, as food quantity and composition modify the responses substantially. Food usually delays peak levels of NSAIDs (and hence onset of action) without affecting total bioavailability. This may not be important when a steady state is achieved, but rapid onset of action is highly relevant for over‐the‐counter use of NSAIDs. The safety of over‐the‐counter use of ibuprofen and naproxen appears to be excellent and comparable with paracetamol. Conclusion The rapid onset of action of NSAIDs is most important during over‐the‐counter use, in which case it may be more appropriate to take the drugs on a fasting stomach.     

Chemical databases: curation or integration by user-defined equivalence?

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The threat represented by toxins: myth or reality?

The reasons underlying our fear of the use of toxins as new weapons different from chemical agents are discussed together with the conditions required for their use on the battlefield. The undeniable scientific contribution of toxins as pharmacological tools for the study of neurosciences and disease genesis and their prophylaxis is emphasized. In conclusion, the threat for mankind constituted by proliferation of this novel class of agents is stressed.     

To treat or not to treat cancer patients with chemotherapy at the end of life?

An interesting prospective British study examined clinical and laboratory data from about 600 patients who died within 30 days of receiving cytotoxic cancer chemotherapy. The vast majority of patients had been treated with palliative rather than curative intent. For about one-quarter of the patients who received palliative chemotherapy, the therapy was considered to have caused or hastened their death. 40% of the patients who died within 30 days following chemotherapy had experienced a serious adverse effect related to the cytotoxic treatment, sometimes requiring hospitalisation. These adverse effects included infections, coagulation disorders, gastrointestinal disorders and renal impairment. Nearly one-quarter of the patients had a poor performance status when chemotherapy was instituted. In particular, more than half of them already had a cancer-related complication when they started the cycle, such as impaired kidney or liver function, hypoalbuminaemia, ascites or pleural effusion. Only 16% of the deaths were discussed with the medical team in a morbidity and mortality meeting. In practice, not administering cytotoxic chemotherapy is sometimes the best solution for patients. Healthcare teams would be well advised to prepare for the (ideally shared) decision on whether or not to treat a terminally ill cancer patient with cytotoxic drugs; by conducting a systematic analysis of the causes of death of other patients treated in the same manner.     

Using motivational interviewing with smokers: Do therapist behaviors relate to engagement and therapeutic alliance?

This study examined whether therapist behaviors consistent with motivational interviewing (MI) were associated with within-session working alliance and client engagement. Forty-six audiotaped counseling sessions were drawn from a group-randomized comparison-controlled smoking cessation trial for public housing residents. Separate raters coded therapist behaviors and client behaviors. Therapist behaviors were coded using the Motivational Interviewing Skill Code. Results indicated that an MI-consistent style (average of the global ratings of collaboration, egalitarianism, and empathy) was positively associated with alliance and engagement, whereas confrontation was negatively related to alliance. Small to moderate effect sizes were found for affirming, asking open-ended questions, confronting, reflecting, and summarizing. Significant covariates include treatment condition, session sequence, and session date. Findings empirically support Miller and Rollnick's [Miller, W. R., & Rollnick, S. (2002). Motivational interviewing: Preparing people for change (2nd ed.). New York: Guilford Press] emphasis on the importance of MI spirit for enhancing alliance and engagement and their findings that any tears/ruptures in the alliance through the use of confrontation could significantly relate to poor outcomes.     

Comparison of Several Multiple Imputation Strategies for Repeated Measures Analysis of Clinical Scales: To Truncate or Not To?

We evaluated via a simulation study several strategies for imputing missing ordinal outcomes in a longitudinal clinical trial, contrasting methods that involve truncation of imputed values outside plausible ranges with those that do not. Our aim was to identify a preferred imputation strategy for estimating treatment difference at study endpoint. Plausible data were simulated via resampling of existing placebo data sets and adding treatment effect; then different imputation strategies were evaluated under missingness at random (MAR) and varying dropout rates. Our conclusion is that imputation methods based on rounding and truncation lead to larger bias than strategies based on simple methods based on (nontruncated) multivariate normal distribution.     

Biological oxidative damage by carbon nanotubes: fingerprint or footprint?

Carbon nanotubes (CNTs) have received much attention for performance and toxicity, but vary substantially in terms of impurity type and content, morphology, and surface activity. This study determined the decrease of antioxidant capacity, defined as biological oxidative damage (BOD), of CNTs-exposed serum. The variability in several physicochemical properties of CNTs and their links to BOD elicited in human serum were explored. Tremendous variation in transition metal type and content (104-fold), specific surface area (SSA, nine-fold), and BOD were observed. Mass specific BOD (mBOD) varied from 0.006-0.187 μmol TEU mg(-1), whereas surface area specific BOD (sBOD) varied from 0.068-0.42 μmol TEU m(-2). The sBOD increased in a stepwise fashion from ～0.1-0.32 μmol TEU m(-2) for tubes with outer diameter less than 10 nm. The mBOD and sBOD may be useful denominators of surface activity and impurity content and assist in designing safer CNTs.     

Brain drain or OE? Characteristics of young New Zealanders who leave.

AIMS: To characterise the emigration patterns of young New Zealanders. METHODS: The 980 members of the Dunedin Multidisciplinary Health and Development Study participating in the "age-26" (1998-1999) assessment provided information about emigration behaviour, qualifications, aspects of physical and mental health and personality. RESULTS: 26% of the sample had moved overseas to live between the ages of 18 and 26, with the United Kingdom and Australia being the most common destinations. Compared to non-emigrants, emigrants had higher IQ scores, were better qualified, leaner and fitter, and had happier and less stress-prone personalities. Based on their planned return date, 63% of emigrants were considered to be on their OE overseas experience (OE, return in <5 years), 18% were defined as brain-drain emigrants (return in >5 years or never) and 18% were uncertain about their return. Brain-drain emigrants were more likely than OE emigrants to leave for better work opportunities, and they were also more likely to go to Australia. However, there were no differences in terms of qualifications, intelligence and personality between OE and brain-drain emigrants. CONCLUSIONS: Most young New Zealanders in this cohort who left for overseas were embarking on their OE. Brain-drain emigrants make up a sizeable minority of emigrants, but appear to possess no more skills than those who plan or choose to return.