A systematic review of barriers and facilitators to participation in randomized controlled trials by Indigenous people from New Zealand, Australia, Canada and the United States.

ISSUE: Many randomized controlled trials (RCTs) are conducted each year but only a small proportion is specifically designed for Indigenous people. In this review we consider the challenges of participation in RCTs for Indigenous peoples from New Zealand, Australia, Canada and the United States and the opportunities for increasing participation. APPROACH: The literature was systematically searched for published articles including information on the barriers and facilitators for Indigenous people's participation in health-related RCTs. Articles were identified using a key word search of electronic databases (Scopus, Medline and EMBASE). To be included, papers had to include in their published work at least one aspect of their RCT that was either a barrier and/or facilitator for participation identified from, for example, design of intervention, or discussion sections of articles. Articles that were reviews, discussions, opinion pieces or rationale/methodology were excluded. Results were analysed inductively, allowing themes to emerge from the data. KEY FINDINGS: Facilitators enabling Indigenous people's participation in RCTs included relationship and partnership building, employing Indigenous staff, drawing on Indigenous knowledge models, targeted recruitment techniques and adapting study material. Challenges for participation included both participant-level factors (such as a distrust of research) and RCT-level factors (including inadequately addressing likely participant barriers (phone availability, travel costs), and a lack of recognition or incorporation of Indigenous knowledge systems. IMPLICATION: The findings from our review add to the body of knowledge on elimination of health disparities, by identifying effective and practical strategies for conducting and engaging Indigenous peoples with RCTs. Future trials that seek to benefit Indigenous peoples should actively involve Indigenous research partners, and respect and draw on pertinent Indigenous knowledge and values. This review has the potential to assist in the design of such studies.

Does extended telephone callback counselling prevent smoking relapse?

This randomized controlled trial tested whether extended callback counselling that proactively engaged ex-smokers with the task of embracing a smoke-free lifestyle (four to six calls delivered 1-3 months after quitting, i.e. when craving levels and perceived need for help had declined) could reduce relapse compared with a revised version of Quitline's standard service (four calls in the first month after quitting which focused primarily on the task of helping ex-smokers deal with daily cravings and now also systematically alerted clients to the upcoming task of adapting to life as a non-smoker). One thousand and four hundred and forty-four smokers or recent ex-smokers were randomized at recruitment: 734 usual care and 710 intervention. An inclusion criterion of subsequently quitting for at least 1 week gave 346 usual care and 352 intervention participants. Seventy-four per cent of intervention participants accepted extra calls and received 4.3 on average but only 1.7 more post-quitting calls than usual care group. No significant differences were found between extended contact and usual care groups on continuous abstinence (both 27% at 12 months) or any other cessation outcome. The tasks of quitting framework introduced in preparation for the trial might have contributed to service improvement in relapse prevention (10% increased quit rate compared with an earlier trial). However, the extra sessions did not provide any benefit.

The challenge of embracing a smoke-free lifestyle: a neglected area in smoking cessation programs.

Relapse prevention theory and practice has focussed on teaching coping skills to deal with withdrawal and temptations to relapse with the result that treatments appear to be effective in reducing relapse over the short term, but not over the longer term. Once cravings subside ex-smokers face a further task of adjusting to a smoke-free lifestyle that involves learning to think and act like a non-smoker. To highlight this task, we operationalized a new conceptual framework that describes three tasks of quitting (the 3Ts): (i) making a quit attempt; (ii) learning to effectively deal with cravings and withdrawal; and (iii) adapting to a smoke-free lifestyle. This was introduced to the Quitline service in Victoria, Australia, in preparation for a randomized controlled trial aimed at testing whether a program of four to six extra callbacks could help ex-smokers with the third task and as a result reduce rates of relapse compared with Quitline's standard callback program. This paper describes the conceptual framework (focussing on the third task) and initial reactions to it from both Quitline advisors and callers. The conceptual framework is now integrated in the service and appears to have changed the way Quitline operates and the apparent expectations of its clients.

CXCL16 is a marker of inflammation, atherosclerosis, and acute coronary syndromes in humans.

OBJECTIVES: This study was designed to determine the association of CXCL16 with inflammation, atherosclerosis, and acute coronary syndromes. BACKGROUND: Vascular inflammation coincides with uptake of modified lipoproteins in the pathogenesis of atherosclerosis. CXCL16 is a protein that shares scavenger receptor function, promoting uptake of modified lipids, with the activities of an inflammatory chemokine. However, the role of CXCL16 in atherosclerosis remains uncertain. METHODS: The effect of inflammatory stimuli on CXCL16 gene and protein expression was studied in macrophages, mice, and humans, and the association of sol-CXCL16 with risk factors, atherosclerosis, and acute coronary syndromes was determined in humans. RESULTS: Endotoxin induction of CXCL16 in human macrophages was attenuated by aspirin, nuclear factor (NF)-kappa-B inhibition and peroxisome proliferator-activated receptor (PPAR)-gamma agonists. Experimental human endotoxemia (n = 6) led to an 8-fold increase in whole-blood CXCL16 messenger ribonucleic acid (p < 0.001) and a 1.7-fold increase in soluble (sol)-CXCL16 (p < 0.001), a cleaved active chemokine. Rosiglitazone-blocked endotoxin induced sol-CXCL16 in mice (p = 0.001), and pioglitazone (n = 28), compared to placebo (n = 28), lowered plasma sol-CXCL16 in metabolic syndrome subjects (p < 0.05). In a nested case-control study of acute and chronic coronary artery disease (n = 699), sol-CXCL16 levels correlated with inflammatory and metabolic risk factors and were associated with chronic coronary artery disease (odds ratio [OR] [95% confidence interval], above vs. below median; 1.60 [1.01 to 2.58]; p = 0.04) and acute coronary syndromes (OR 2.52 [1.32 to 4.82], p = 0.005) following adjustment for established risk factors, medications, and C-reactive protein levels. CONCLUSIONS: Our findings suggest that CXCL16 may play a pro-inflammatory role in human atherosclerosis, particularly in acute coronary syndrome.

Diet-dependent cardiovascular lipid metabolism controlled by hepatic LXRalpha.

The high-cholesterol/high-fat Western diet has abetted an epidemic of atherosclerotic cardiovascular disease, the leading cause of death in industrialized nations. Liver X receptors (LXRs) are oxysterol sensors that are required for normal cholesterol and triglyceride homeostasis, yet synthetic LXR agonists produce undesirable hypertriglyceridemia. Here we report a previously unrecognized role for hepatic LXRalpha in the links between diet, serum lipids, and atherosclerosis. A modest increase in hepatic LXRalpha worsened serum lipid profiles in LDL-receptor null mice fed normal chow but had the opposite effect on lipids and afforded strong protection against atherosclerosis on a Western diet. The beneficial effect of hepatic LXRalpha was abrogated by a synthetic LXR agonist, which activated SREBP-1c and its target genes. Thus, the interplay between diet and hepatic LXRalpha is a critical determinant of serum lipid profiles and cardiovascular risk, and selective modulation of LXR target genes in liver can ameliorate hyperlipidemia and cardiovascular disease.

An inflammatory cascade leading to hyperresistinemia in humans.

BACKGROUND: Obesity, the most common cause of insulin resistance, is increasingly recognized as a low-grade inflammatory state. Adipocyte-derived resistin is a circulating protein implicated in insulin resistance in rodents, but the role of human resistin is uncertain because it is produced largely by macrophages. METHODS AND FINDINGS: The effect of endotoxin and cytokines on resistin gene and protein expression was studied in human primary blood monocytes differentiated into macrophages and in healthy human participants. Inflammatory endotoxin induced resistin in primary human macrophages via a cascade involving the secretion of inflammatory cytokines that circulate at increased levels in individuals with obesity. Induction of resistin was attenuated by drugs with dual insulin-sensitizing and anti-inflammatory properties that converge on NF-kappaB. In human study participants, experimental endotoxemia, which produces an insulin-resistant state, causes a dramatic rise in circulating resistin levels. Moreover, in patients with type 2 diabetes, serum resistin levels are correlated with levels of soluble tumor necrosis factor alpha receptor, an inflammatory marker linked to obesity, insulin resistance, and atherosclerosis. CONCLUSIONS: Inflammation is a hyperresistinemic state in humans, and cytokine induction of resistin may contribute to insulin resistance in endotoxemia, obesity, and other inflammatory states.

The effectiveness of callback counselling for smoking cessation: a randomized trial.

AIMS: The development of acceptable, widely available and effective smoking cessation methods is central to public health strategy for tobacco control. We examined the effectiveness of a telephone callback counselling intervention, compared to the provision of self-help resources alone. METHODS: Participants were 998 smokers calling a state-wide "Quitline" service randomly allocated to either callback counselling or ordinary care. The callback condition consisted of a series of brief counselling calls at strategic times in addition to ordinary care. The number of calls varied according to caller needs, and most occurred generally just before the person's quit day and in the week or two after it. The service was delivered by trained telephone counsellors. RESULTS: At the 3-month follow-up, significantly more participants in the callback group (24%) reported that they were quit, compared to those in the usual care comparison group (13%). The difference in point prevalence of smoking declined to 6% by the 12-month follow-up. Using sustained abstinence there was a significant benefit of callback counselling at 12-month follow-up. Treating dropouts as smokers reduced the overall magnitude of the effects somewhat. The benefit of callbacks was to marginally increase quit attempts and to significantly reduce relapse. CONCLUSION: Our findings are consistent with those of other studies demonstrating benefits of callback telephone counselling to facilitate cessation. Such counselling provides a flexible, relatively inexpensive and widely available form of cessation service. It appears to encourage a greater proportion of quit attempts and to reduce the rate of relapse among those quitting. Further research is required to determine ways to enhance effectiveness, particularly studies of how to reduce relapse.

Public reaction to Victoria's "2 Fruit 'n' 5 Veg Every Day" campaign and reported consumption of fruit and vegetables.

BACKGROUND: The Victorian "2 Fruit 'n' 5 Veg Every Day" campaign was aimed at increasing awareness of the need to eat more fruit and vegetables and encouraging increased consumption of these foods in the Australian state of Victoria. The demand-side component of the campaign, which had television advertising as a centerpiece, ran from 1992 to 1995. METHODS: Annual postcampaign telephone surveys of approximately 500 Victorians ages 20 and over were conducted with the aim of examining public awareness of the campaign, beliefs about desirable eating habits for fruit and vegetables, and reported consumption of these foods. RESULTS: Over the years, patterns in the level of public awareness, reported consumption, and beliefs about appropriate levels of consumption have tended to parallel changes in the level of mass media investment. During the campaign's most intense period of promotional activity, significant increases in all of these variables occurred. CONCLUSIONS: The results suggest that significant achievements can be made with relatively small-budget mass media promotion of dietary recommendations, especially when part of a more comprehensive program. However, campaigns may need to be adequately resourced for several years if sustained change is to be achieved.

Alcohol use among Australian secondary students in 1993.

The prevalence of alcohol consumption among Australian secondary students in 1993 was estimated from a survey of 22 696 students aged between 12 and 17 years. A random, representative sample of schools from all education systems (government, Catholic and independent) was selected and a sample of 80 students from each school was randomly selected from predetermined year levels. Students completed an anonymous, self-administered survey on their drinking behaviours. Results showed that drinking was common, with 46% of female and 50% of male 17-year-olds having drunk on at least one of the 7 days prior to the survey (defined as current drinkers). Among 12-17-year-olds who were current drinkers, 27% of males had five or more alcoholic drinks on at least one drinking ("heavy drinking") while 43% of girls had had three or more drinks ("heavy drinking"). Among current drinkers aged 12-15 years, 10% of boys and 12% of girls had "binged" (for boys drinking eight or more drinks in one session, for girls having six or more drinks at one session) while among current drinkers aged 16 and 17 years the corresponding proportions were 33% of boys and 30% of girls. After controlling for age, sex, school type and state, the proportion of 12-15-year-olds who were current drinkers rose from 24% to 26% between 1990 and 1993. Among 16 and 17-year-olds, the proportion of current drinkers in 1993 (47%) was the same as that found in 1990, although there were more heavy drinkers and binge drinkers in 1993 than in 1990.

Prevalence of cigarette smoking among Australian secondary school students in 1993.

The prevalence of cigarette smoking in Australian secondary school students in 1993 was estimated from a survey of 22 696 12- to 17-year-old students from 332 secondary schools (and feeder schools) in all states and the Northern Territory. Self-administered questionnaires were answered anonymously by groups of up to 20 students selected randomly from school rolls, a method that replicated previous surveys in 1984, 1987 and 1990. Current smoking (smoking at least one cigarette in the week preceding the survey) at 12 years of age was 8 per cent in boys and 7 per cent in girls, but in those 17 years of age the prevalence was much higher (28 per cent of boys, 31 per cent of girls). Age was also associated with the mean number of cigarettes smoked per week by current smokers (8.6 in boys and 7.0 in girls at age 12 and 43.8 in boys and 32.0 in girls at age 17). After controlling for sex, age, school type and state of residence, the percentage of 12- to 15-year-olds who were current smokers rose from 15.7 per cent to 17.5 per cent between 1990 and 1993, an effect that was more pronounced in boys. On the other hand, the mean number of cigarettes smoked by 12- to 15-year-old current smokers dropped from 23 per week to 19.5, and the reduced consumption was greatest in boys. Furthermore, there was no increase in the proportion of students who smoked on three or more days per week, which suggests the increase was limited to occasional, casual or social smoking.