Does schizophrenia influence cannabis use? How to report the influence of disease liability on outcomes in Mendelian randomization studies

Posted on by kz.davey-smith

The recent Nature Neuroscience paper by Pasman et al entitled “GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia” (see below) provides important and novel insights into the aetiology of cannabis use and its relationship with mental health. However – in its title and elsewhere – it subtly misrepresents what the Mendelian randomization (MR) [1] analyses it presents actually show. MR analyses are increasingly being reported as demonstrating the effect of a disease (in this case schizophrenia) on the outcome, through using genome wide significant variants associated with risk of the disease on the outcome (which can be a behavior, such as cannabis smoking in the present paper, a measured trait or a second disease).

MR analyses are often carried out using summary data, where the exposure and outcome GWAS come from separate samples. In such analyses interpretation is not to apparent effects of the disease itself, but to the phenotypic effects of genetic liability to that disease. Typically, only a tiny proportion of participants in the outcome GWAS datasets will actually have experienced the disease – in this case particularly so given the low participation rate of people with schizophrenia in most studies in the general population. Indeed, MR studies can be carried out in datasets where there are no individuals with the outcome (e.g. datasets collected amongst an age group in whom the outcome will have occurred very rarely, if ever). Such analysis may reveal apparent, but impossible, effects of the disease on outcome phenotypes. To use MR analyses to investigate the causal effect of a disease on outcomes would require individual-level data with recorded disease events and subsequent follow-up. Analytical approaches to such data have, as yet, not been published.

The widespread misrepresentations of such MR studies have important implications, not just in terms of how the results are interpreted, but also how they are applied. One valuable contribution of MR studies is that they can identify modifiable exposures that can be the target of interventions. If it is recognized that what is being shown is an effect of liability to disease on an outcome, then interventions targeting the mechanisms of this liability would have benefits even in individuals who are unlikely to go on to develop the disease, including those at low risk of the disease for other reasons. For example, targeting breast cancer liability may have benefits in men if this liability influenced diseases that are common in men. If, however, it is the disease itself which has the effect, then the interventions would be targeted at those likely to develop disease: only women, in the case of breast cancer liability. It may be that schizophrenia does indeed lead to cannabis use, but the analyses reported by Pasman et al show only that liability to schizophrenia leads to cannabis use.

The point is a subtle one – we have both used similar language in the past in articles reporting MR analyses on which we are authors. Indeed, one of us (MM) was an author on the Pasman et al paper (and contributed principally to the MR analyses and their interpretation) but failed to suggest the correct phrasing.  Fortunately, the title and discussion will be changed to address this problem so that the enduring version of the paper captures this importance nuance (unfortunately, the original headline has already been repeated elsewhere [2]). However, it is a widespread and underappreciated point of interpretation in MR studies, and we feel that this presents a useful opportunity to highlight it. It also illustrates that methodologies, and the interpretation of the results they generate, continue to evolve, illustrating the need to interpret past work (including our own!) through the lens of current approaches.

[1] Davey Smith G, Ebrahim S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease?  Int J Epidemiology 2003;32:1-22.

[2] Andrae LC. Cannabis use and schizophrenia: Chicken or egg?  Sci Transl Med 2018;10:eaav0342.

The House of Commons Science and Technology Committee reports on e-cigarettes

Posted on by Sarah Burrows-Weeks

Written by Jasmine Khouja, PhD Student, Tobacco and Alcohol Research Group

Today sees the publication of a report on electronic cigarettes (e-cigarettes) by the House of Commons Science and Technology Committee. This compiles evidence from over 100 pieces of written submissions and five oral sessions, and highlights key issues around reducing harm, promoting smoking cessation and effectively regulating e-cigarettes. Since the report is quite long, we’ve tried to extract the main messages.

The report takes a relatively positive stance on e-cigarettes, encouraging use for smoking cessation and suggesting a more accepting approach to e-cigarettes in public spaces. This is in contrast to other countries, such as Australia, where a ban is in place due to the lack of long-term research on the health impact of using e-cigarettes.

Reducing harm

The general consensus from a variety of sources is that e-cigarettes are less harmful than combustible cigarettes. However, a frequent theme is that this does not mean that e-cigarettes are ‘safe’, and the report is careful to emphasise that e-cigarettes are not completely harmless. The relative harm of heat-not-burn tobacco products compared to combustible cigarettes is less clear. There is a lack of independent evidence as the majority of data on the safety and emissions of these product has come from Philip Morris, a major tobacco company.

The long-term effects of using e-cigarettes are currently unknown. It is difficult to assess the comparative harm of e-cigarettes without also measuring the effects of prior smoking, since there are very few long-term e-cigarette users who have never smoked. Exposure to second-hand e-cigarette vapour has been similarly difficult to assess, but since potentially harmful compounds emitted are present only at very low levels second-hand vapour is unlikely to be harmful.

E-cigarettes have become a popular tool for quitting smoking and an estimated 16,000 to 22,000 people who would not have quit using alternative products or willpower alone have successfully quit each year by using e-cigarettes. Although these figures are promising, there is a lack of high-quality evidence from randomised control trials showing how effective e-cigarettes are when quitting smoking. Other evidence has been inconclusive due to the low quality of some studies.

Despite fears that e-cigarettes may act as a ‘gateway’ to smoking, current evidence does not show that using e-cigarettes causes people to start smoking. Although there is a link between e-cigarette use and subsequent smoking initiation, very few never smokers regularly use e-cigarettes, so any causal link would have a limited impact on smoking rates.

Smoking cessation

Providing e-cigarettes on prescription could encourage smokers to try e-cigarettes without barriers such as money as well as give them more confidence in the product being less harmful than cigarettes. The report concludes that e-cigarettes should be available to those in NHS mental health services given high rates of smoking in this group.

NHS England were unable to provide evidence for how they were addressing this issue. They were unable to provide a representative because there is no one individual responsible centrally with ‘oversight’ of e-cigarette policies across NHS mental health trusts. The report criticises this, stating it was concerning and that a position should be created as a matter of urgency.

E-cigarettes are generally prohibited in closed spaces such as workplaces, public transport and restaurants and vapers are usually encouraged to vape outside within designated ‘smoking’ areas. Since second-hand vapour is unlikely to be harmful, these policies may be more harmful than beneficial; frequently exposing vapers to cigarettes and cigarette smoke may increase the likelihood that they will relapse to smoking.

Regulation

E-cigarettes are currently regulated under the Tobacco Products Directive (TPD; see our previous blog) if you want to learn more about these regulations). As part of this directive, the Medicines and Healthcare products Regulatory Agency must be notified before any e-cigarette or e-liquid can be sold in the UK.

Four key criticisms of the TPD were identified in the report: i) unnecessary limits on nicotine strength of refill liquids which may lead to failed quit attempts, ii) unnecessary tank size restrictions which may lead to failed quit attempts, iii) blocking advertising the relative harm-reduction of e-cigarettes which may discourage quit attempts, and iv) the ineffective notification scheme for e-cigarette ingredients which slows innovation.

Some TPD regulations are optional and give freedom to governments to be as restrictive as they feel necessary. Scotland has been more restrictive than England in their regulations by banning certain advertising of vapour products. Currently, health claims are banned from all media advertising of e-cigarettes without a medical license (of which none is currently available). The Advertising Standards Authority is currently reviewing the legislation on e-cigarette advertising and health claims and are considering allowing this in the future.

Unsurprisingly, there is uncertainty about the future regulation of e-cigarettes due to Brexit. Regulation of e-cigarettes may change after leaving the European Union and it is unclear what these changes may be or what potential impact increased flexibility in regulating e-cigarettes could have.

Conclusions

The report is comprehensive and raises some interesting questions particularly about the lack of NHS involvement in developing strategies for smoking cessation that utilise e-cigarettes. It will be interesting to see if the NHS responds to these criticisms by taking action. I am also interested to see what Brexit will mean for the regulation of e-cigarettes in the UK, given the criticisms of TPD regulations.

The full report can be accessed here: [The House of Commons Science and Technology Committee reports on e-cigarettes]

 

Why I took part in the “Preregistration Challenge”

Posted on by annablackwell

By Sarah Peters

The preregistration of study protocols has a long history in clinical trials, but is a more recent innovation in many other areas. The hope is that it will help counter the “reproducibility crisis” in psychological science – the failure of many published findings to replicate reliably. Here I discuss my experience with the Open Science Framework “Preregistration challenge”, and argue for more widespread adoption of preregistering reports.

There is an ongoing methodological crisis in psychological science – the reproducibility crisis refers to the failure of many scientific findings to be replicated. The Reproducibility Project, a recent initiative led by Professor Brian Nosek at the University of Virginia, aimed to identify the scale of this crisis. A large collaboration between 270 project members reran 100 published psychological experiments, and found that just 36% of the initial findings were replicated. Similarly, some classic textbook experiments have proven difficult to replicate, and publication bias – whereby positive findings are more likely to be published and negative findings to be dismissed – plagues the field.

Given this, scientists are exploring how to improve the way we conduct research and thereby improve the quality of what we produce. One suggestion is to preregister our research question, methods and analysis plan in advance of data collection. It is hoped that public preregistration will limit analytical flexibility and post hoc hypothesising, thereby improving the transparency and robustness of research findings.

Curious about the benefits of preregistration, and to see how it differed from the way I’d previously conducted my research, my colleagues and I published a preregistration for a recent study on Open Science Framework (OSF). We were interested in whether Cognitive Bias Modification, a psychological intervention designed to shift the emotional interpretation of faces, would impact clinically-relevant outcomes. We also entered the study into OSF’s (ongoing!) Preregistration Challenge, which offers the chance to win a $1,000 prize to 1,000 researchers who go from preregistration to publication.

Preregistering our study did require a greater time commitment prior to running it, but thinking about our predictions, design, and analyses meant that we could spot any potential issues and improve our experimental design before we collected data (i.e., before it was too late!). As a preregistration is public and cannot be changed after it’s published, it forced us to think more carefully about our decisions. For example, thinking more carefully about whether our data would truly answer our question made us wonder whether the emotional biases we wanted to study might be more prominent when an individual is under stress, so we decided to include another task to measure this. Also, by knowing which statistical analyses we would conduct before recruiting participants we could ensure that our study was adequately powered and would meet the assumptions of the planned analyses.

Initially I was concerned that this approach could be limiting. What if we found something interesting that we hadn’t expected and wanted to run additional analyses to probe it? But a preregistered report doesn’t prevent that – it simply means that you would (honestly and transparently!) report those analyses as exploratory. This protection against HARKing (hypothesising after the results are known) is important; separating analyses as planned versus exploratory can prevent overconfidence in weaker findings and the publication of attractive, but uncertain, positive findings.

Following data collection, we went back to our preregistration. It was here that our earlier time investment paid off; once our data were cleaned we could immediately run our planned analyses, and much of the manuscript writing (introduction and methods) was already done. We also ran a number of exploratory analyses, such as whether our results were moderated by participants’ anxiety scores. We subsequently published our findings in the academic journal Royal Society Open Science, and were thrilled to receive one of the latest $1,000 Preregistration Challenge prizes for bringing our study from preregistration to publication!

While interpreting findings and making discoveries is an important aim of scientific research, it is just as important to continuously scrutinise the scientific method. As a scientist, there is no question that seeing data can influence my decisions and interpretations. However, the adoption of preregistration can eliminate this, make the process easier in the long term, and improve research quality overall.

Professor Nosek and other members of the Reproducibility Project argue that, “Progress in science is marked by reducing uncertainty about nature”. But, if scientific findings have not or cannot be replicated, we can’t be certain that they exist. Preregistration is a simple change to the way we do research that can help to halt the reproducibility crisis and produce effective and credible science.

Read more about how to take part in the Preregistration Challenge here.

See Peters et al.’s preregistration here, and the published study here.

Sarah Peters can be contacted via email at: s.peters@bristol.ac.uk.

Can cognitive interventions change our perception from negative to positive, and might that be useful in treating depression?

Posted on by annablackwell

By Sarah Peters

Have you ever walked away from a social interaction feeling uncomfortable or anxious? Maybe you felt the person you were talking to disliked you, or perhaps they said something negative and it was all you could remember about the interaction. We all occasionally focus on the negative rather than the positive, and sometimes ruminate over a negative event, but a consistent tendency to perceive even ambiguous or neutral words, faces, and interactions as negative (a negative bias), may play a causal role in the onset and rate of relapse in depression.

A growing field of psychological interventions known as cognitive bias modification (CBM) propose that by modifying these negative biases it may be possible to intervene prior to the onset of depression, or prevent the risk of subsequent depressive episodes for individuals in remission. Given that worldwide access to proven psychological and pharmacological treatments for mood disorders is limited, and that in countries like the UK public treatment for depression is plagued by long waiting lists, high costs, side effects, and low overall response rates, there is a need for effective treatments which are inexpensive, and both quick and easy to deliver. We thought that CBM might hold promise here, so we ran a proof of principle trial for a newly developed CBM intervention that shifts the interpretation of faces from negative to positive (a demonstration version of the training procedure can be seen here). Proof of principle trials test an intervention in a non-patient sample, which is important to help us understand a technique’s potential prior to testing it in a clinical population – we need to have a good idea that an intervention is going to work before we give it to people seeking treatment!

In this study, we had two specific aims. Firstly, we aimed to replicate previous findings to confirm that this task could indeed shift the emotional interpretation of faces. Secondly, we were interested in whether this shift in interpretation would impact on clinically-relevant outcomes: a) self-reported mood symptoms, and b) a battery of mood-relevant cognitive tasks. Among these were self-report questionnaires of depressive and anxious symptoms, the interpretation of ambiguous scenarios, and an inventory of daily stressful events (e.g., did you “wait too long in a queue,” and “how much stress did this cause you on a scale of 0 to 7”). The cognitive tasks included a dot probe task to measure selective attention towards negative (versus neutral) emotional words, a motivation for rewards task which has been shown to measure anhedonia (the loss of pleasure in previously enjoyed activities), and a measure of stress-reactivity (whereby individuals complete a simple task under two conditions: safe and under stress). This final task was included because it is thought that the negative biases we were interested in modifying are more pronounced when an individual is under stress.

We collected all of our self-report and cognitive measures at baseline (prior to CBM), after which participants underwent eight sessions (in one week) of either CBM or a control version of the task (which does not shift emotional interpretation). We then collected all of our measures again (after CBM). In order to be as sure of our results as possible, there were a number of critical study design features we used. Our design, hypotheses, and statistical analyses were pre-registered online prior to collecting data (this meant that we couldn’t fish around in our data until we found something promising, then re-write our hypotheses to make that result seem stronger). We also powered our study to be able to detect an effect of our CBM procedure. This meant running a statistical calculation to ensure we had enough participants to be convinced by any significant findings, and their potential to be clinically useful. This told us we needed 104 individuals split evenly between groups. Finally, our study was randomised (participants were randomly allocated to the intervention group or the control group), controlled (one group underwent an identical “placebo” procedure), and double-blind (only an individual who played no role in recruitment or participant contact knew which group any one participant was in).

So, what did we actually find? While the intervention successfully shifted the interpretation of facial expressions (from negative to positive), there was only inconclusive evidence of improved mood and the CBM procedure failed to impact most measures. There was some evidence in our predicted direction that daily stressful events were perceived as less stressful by those in the intervention group post-CBM, and weaker evidence for decreased anhedonia in the intervention group. In an exploratory analysis, we also found some evidence that results in the stress-reactivity task were moderated by baseline anxiety scores – for this task, the effects of CBM were only seen in individuals who had higher baseline anxiety scores. However, exploratory findings like this need to be treated with caution.

Therefore, as is often the case in scientific research, our results were not entirely clear. However, there are a few limitations and directions for future research that might explain and help us to interpret our findings. Our proof of principle study only considered effects in healthy individuals. Although these individuals were clearly amenable to training, and may indeed have symptoms of depression or anxiety without a clinical diagnosis, our observation that more anxious individuals appeared to be more affected by the intervention warrants research in clinical populations. In fact, a reasonable parallel to the effects observed in this study may be working memory training, which does not transfer well to other cognitive operations in healthy samples, but shows promise as a tool for general cognitive improvement in impaired populations.

Future research is also needed to disambiguate the tentative self-report stress and cognitive anhedonia effects observed here. One possibility, for example, is that the 104 participants we recruited were not enough to detect an effect of transference from CBM training to other measures (the size of which is unknown). Given the complexity of any mechanism through which a computerised task could shift the perception of faces and then influence behaviour, it is likely that a larger sample is necessary. While it could be argued that if such a large group of individuals is warranted to detect an effect, that effect is likely too small to be clinically useful, we would argue that even tiny effects can indeed be meaningful (e.g., cancer intervention studies often identify very small effects which can have a meaningful impact at a population level).

Another explanation for our small effects is that while one week was long enough to induce a change in bias, it may not have been long enough to observe corresponding changes in mood. For instance, positive interpretation alone may not be enough – it may be that individuals need to go out into the world and use this new framework to have personal, positive experiences that gradually improve mood, and this process may take longer than one week.

Overall, this CBM procedure may have limited impact on clinically-relevant symptoms. However, the small effects observed still warrant future study in larger and clinical samples. Given the large impact and cost of mood disorders on the one hand, and the relatively low cost of providing CBM training on the other, clarifying whether even small effects exist is likely worthwhile. Even if this procedure fails to result in clinical improvement, documenting and understanding the different steps in going from basic scientific experimentation to intervening in clinical samples is crucial for both the scientific field and the general public to know. The current study is part of a body of research which should encourage all individuals who are directly or indirectly impacted by depression or other mood disorders. Novel approaches towards understanding, preventing, and treating these disorders are constantly being investigated, meaning that we can be hopeful for a reduction in the devastating impact they currently have in the not so distant future.

Read the published study here

Sarah Peters can be contacted via email at: s.peters@bristol.ac.uk 

Does calorie and unit information influence our drinking behaviour?

Posted on by annablackwell

By Olivia Maynard

Over the past two years we’ve invited hundreds of people into the lab to drink beer. Unfortunately, we weren’t there to socialise; this was in the name of science. We wanted to know whether giving people information about the number of units and or calories in their beer influenced how much they drank and their perceptions of drinking.

There are strong arguments for including this information: providing unit information may increase knowledge about alcohol consumption and calorie information may help drinkers choose lower calorie (and as a result lower unit) beverages. However, we also wondered whether there might be some unintended consequences of providing this information, particularly for those who are highly motivated to drink. What if unit information simply allows these drinkers to choose higher strength drinks and calorie information only discourages them from eating more, not drinking less? What if discussion around mandatory unit and calorie labelling is distracting us from the bigger issues: health warnings, minimum unit pricing, improving treatment for alcohol dependence and stopping alcohol advertising to young people, to name a few?

So, with this healthy level of scepticism, we set about inviting 264 regular alcohol consumers (mostly undergraduate students) to attend a lab session where they were given some beer and completed some taste ratings. What participants didn’t know was that they had been randomly assigned to one of four conditions. One group had information about the calorie and unit content of the beers, one group just got calorie information, another had just unit information, and the final group got no information at all. As well as measuring how much beer they drank, we also asked participants to reflect on the likely impact of unit and calorie information on their drinking behaviour.

You can read all the results in our (open access) paper that was published this week in the journal Alcohol and Alcoholism. If you want the concise version: we found no evidence that either unit or calorie information influenced how much beer people consumed and we found a lot of variation in the amount people drank.

However, it was our analysis of participants’ thoughts on unit and calorie information that proved vital to understanding what was going on here. Our participants told us that their main motivation for drinking alcohol was usually to get drunk; where unit information was perceived as being helpful, this was to help them choose the highest strength drink. Unit and calorie information was seen as distracting from the social aspect of drinking, and although some participants felt that calorie information might reduce consumption, most thought it would affect others, not themselves. Some people thought that calorie information could be misused by encouraging people to eat less (to compensate), rather than drink less.

It’s interesting that even though the unit and calorie information was very visible in our study (on a piece of paper, presented for 10 minutes), those who had received this information were still very inaccurate when it came to reporting how many units and calories were in their drinks. They basically didn’t seem to have read or engaged with it. If they’re not reading it in this context, is it likely that drinkers will read this information when it’s printed in tiny font on the back of the bottle?

So, what does this all mean for any plans to introduce unit and calorie information? Our study only really tells us about the potential impact of unit and calorie information among young adults (many of whom were students) who tend to drink to get drunk. However, our findings do call into question whether mandatory unit and calorie labelling on its own would reduce how much people drink, and also highlights potential negative unintended consequences of providing this information.

Despite some of these potential unintended consequences, there are still reasons to include unit and calorie information, if only because it’s a consumer right (you know how many calories are in just about everything else you consume). However, perhaps more effort needs to be placed on making this information more engaging and embedding it into public understanding of recommended drinking levels. Coincidentally, an analysis of the public’s awareness of new national alcohol guidelines was also published yesterday. This report argues that although the public have a relatively high awareness of what the guidelines are, they should be put into context by increasing the public’s awareness of the links between alcohol and cancer. Perhaps using health messages such as ‘Drinking alcohol regularly is linked to long-term risks such as cancer’, alongside unit and calorie information, might result in more meaningful changes in attitudes and behaviours around drinking. I feel another study coming on….

Olivia Maynard can be found on Twitter at @OliviaMaynard17

A Summary of the E-cigarette Summit US 2017

Posted on by annablackwell

By Jasmine Khouja

The first E-cigarette Summit US was held in Washington DC on the 8th May 2017. The one-day event brought together researchers, medical professionals and members of industry from all over the US as well as many from the UK (where the organisers have held E-cigarette Summits successfully for the past four years). A review of the safety of e-cigarettes was followed by a review of the regulations that have been proposed in the US. Throughout the day, comparisons were made between the UK and US, particularly in the approaches taken to health messages and regulation of e-cigarettes. In Professor Kenneth Warner’s opening address, he suggested that there are two types of researcher in the field of e-cigarette research: sceptics, who are focussed on potential harm and protecting children regardless of the potential harm reduction for adult smokers, and enthusiasts, who are focussed on potential benefits to public health due to smoking cessation which could outweigh the potential risk to children. By this definition, the majority of researchers who presented evidence appeared to be enthusiasts.

Here are some highlights from the summit:

Evidence Updates

The majority of presentations suggested that previous research has overestimated the health risks of e-cigarettes by using inappropriate methods such as testing the toxicants produced from vaping using temperatures which are not used by vapers. Recently, Dr Konstantinos Farsalinos and his team have attempted to replicate such findings with maximum temperatures used by vapers and are yet to find evidence that supports the previous findings.

Dual use was also a common theme in the presentations; dual use is the use of e-cigarettes alongside smoking (or other tobacco product use depending on the definition used). However, as Dr Andrea Villanti pointed out, context is key when researching dual use; two people defined as dual users may be extremely different. For example, one dual user may smoke one cigarette a week and vape daily and another may vape once a week and smoke 20 cigarettes a day. With this in mind, Dr Robin Mermelstein’s research focussed on dual users and found that common reasons for using e-cigarettes were using e-cigarettes as a substitute for cigarettes, to cut down their cigarette consumption, to curb their cravings in places they were not allowed to smoke and because they were trying to quit smoking.

Public health

Professor Linda Bauld provided evidence that public health messages can impact the effectiveness of e-cigarettes as a smoking cessation tool. In the UK, there is generally a positive stance taken towards the use of e-cigarettes for smoking cessation among the public health community, however this stance has not been adopted in the US. It was suggested numerous times that consensus among the public health community could help smokers to quit and could help the medical community to provide accurate advice.

Regulations

New regulations for e-cigarettes are being proposed for the US in the Cole-Bishop proposal. Under these regulations, the e-cigarette market would essentially be frozen, preventing improvements to devices in safety and efficacy according to Deborah Arnott. However, Matthew Myers would disagree and sees flexibility in the FDA regulations which he believes are absolutely necessary.

Overall, the summit was extremely informative and highlighted the need to clearly communicate the findings of well-designed research to the public in order to maximise the potential for reducing smoking rates with use of e-cigarettes.

Action for Brain Injury Week

Posted on by annablackwell

By Eleanor Kennedy

It’s Action for Brain Injury Week this week (8th – 14th May), a campaign run by the non-profit brain injury association Headway.  This year the campaign is all about “A New Me”, giving a platform to survivors and their families to discuss how life-changing a brain injury can be. In honour of the campaign, I’m writing a summary about my PhD research on mild traumatic brain injury.

Traumatic brain injury (TBI) is an injury to the head that results in an alteration in consciousness. My work focuses on mild TBI, which injury involves symptoms such as confusion/disorientation, loss of consciousness of less than 30 minutes and/or memory loss around the event that led to the injury.

I’m interested in how mild TBI in youth may be associated with later behaviour. Initially I conducted a systematic review of the literature and found that there was evidence for an association between childhood mild TBI and behaviours such as substance use, committing crimes and behavioural issues. However, this was based on a small number of studies and there were some limitations to be addressed.

A key issue was the use of appropriate control participants. In this kind of research, the behaviour of participants with mild TBI has been compared to that of participants with no injuries. These control participants are usually similar to the mild TBI group in terms of demographic factors such as age, gender and socioeconomic background. However, these similarities do not consider injury factors that could also have an impact on behaviour, for example pain, absence from school, and the trauma of having an injury. A second control group that includes participants with a non-head-related injury addresses this issue.

In my own research, I use data from the Avon Longitudinal Study of Children and Adolescents (ALSPAC). This is a birth cohort that began in the early nineties when over 14, 000 pregnant women were recruited; biological, genetic, environmental and psychological information has been gathered on participating families ever since. Participants and their parents have answered questions relating to head injury and fractures at many time points across the children’s life time. It is possible to have a group with mild TBI, a group with broken bone history and a group with neither injury.

So far, we have explored the association between mild TBI from birth to age 16 years and risk behaviour at age 17 years. We found that participants with a mild TBI were more likely to use alcohol to a hazardous level than participants with a broken bone and participants with no injury. This is in line with previous research, and has important implications for recurrent TBI and recovery from TBI. Another finding was that participants with either a mild TBI or a broken bone were more likely to commit offences – suggesting that there may be common risk factors for acquiring an injury and criminal behaviour. For example, an individual who has the personality trait of sensation seeking could potentially be more likely to get into risky situations leading to injuries and to commit offences.

I recently presented these findings at the International Brain Injury Association’s 12th World Congress in New Orleans. At the conference, there was an exhibition of masks created as part of a project called ‘Unmasking Brain Injury’. Each mask was designed and decorated by a survivor of brain injury to share their experience; each mask was as unique as the individuals’ story. Projects that give a voice to people living with a brain injury, such as ‘A New Me’ campaign, are a reminder of the challenges that are faced when dealing with a brain injury. It’s a privilege to contribute research to this field and to listen to the voices of those experiencing it to promote awareness and compassion.

A Summary of the E-cigarettes Summit 2016

Posted on by rebeccalawn

by Jasmine Khouja @jasmine_khouja

On the 17th November I attended the E-cigarette Summit 2016 at the Royal Society in London. The summit brought together researchers, policy-makers, smoking cessation services and industry members to hear about the latest research, developments and challenges in the e-cigarette domain.

The summit was a one-day event packed full of information with 20 fast-paced (10-20 minutes) talks and 4 panel discussions. My five take home points from the summit were:

  1. Communication

One point which was raised on multiple occasions was that good communication of the research into e-cigarettes is key to the public understanding the risks and benefits of e-cigarette use. Unfortunately, the consensus was that the communication of e-cigarette research to the public is poor. Astonishingly, one speaker commented that someone had asked their daughter: “Is your dad still selling e-cigarettes and killing people?” This demonstrates how badly e-cigarettes have been portrayed, despite general consensus that they are much less harmful than cigarettes. Researchers are trying to communicate their research but face hurdles; some journals may be less likely to publish articles that are positive about vaping, meaning that it is harder to publish evidence that vaping is not as bad for you as cigarettes. The media are also hampering researchers’ efforts as they prefer stories which are anti-vaping and sometimes draw inaccurate conclusions from the evidence, which makes for more interesting stories. However, effective communication of the research is possible: Professor Peter Hajek and Dr Alex Freeman provided some useful advice to researchers which included not inferring human risks from animal studies, ensuring risks are directly compared to those of smoking, being a trustworthy source by being competent, honest and reliable, and providing neutral information without recommendations allowing the public to make their own informed decisions.

  1. The British Medical Association’s Guidelines

Communication of the benefits and risks of e-cigarettes isn’t limited to publications and the media; doctors are being asked about e-cigarettes by patients. Despite the evidence that the research community has provided that e-cigarettes are less harmful than cigarettes, the British Medical Association are yet to update their guidelines to encourage smokers to switch to e-cigarettes. There seemed to be apprehension stemming from the lack of known long-term effects, despite the fact that we know there are vastly fewer and reduced amounts of toxicants in e-cigarettes compared to cigarettes meaning the likelihood of long-term effects as bad as or worse than smoking are extremely unlikely.

  1. Recent Research

Many new studies were presented but the study that really caught my attention was discussed by Dr Lynne Dawkins. Lynne provided evidence for increased puffing behavior when participants are given lower doses of nicotine in their e-cigarettes [1]. She concluded that inhaling more vapour to receive the same amount of nicotine exposes vapers to unnecessary amounts of toxicants. This is very topical as the regulations set out by the Tobacco Products Directive (TPD) which will be fully implemented by May 2017 limit doses to 20 mg/mL meaning that some higher dosage (36 mg/mL) users may expose themselves to extra toxicants to receive the levels of nicotine they need when the higher dosage product become unavailable in the next six months.

  1. The Tobacco Products Directive

The TPD provides some form of regulation for e-cigarette manufacturers and distributors. The inclusion of e-cigarettes in the TPD was controversial due to e-cigarettes not containing tobacco and the restrictive nature of the regulations which were seen as unnecessary by some users and industry members. Part of the regulations included the thorough testing of e-cigarette products to ensure they were safe and the publication of the contents (including toxicants) so that the public could make informed decisions. To my dismay, I was informed that the information submitted by the e-cigarette companies so far will not be made publically accessible for roughly six months due to a system error. I was also informed that compliance with the regulations was low and that age of sale restrictions in particular did not seem to be being enforced. The system and enforcement of the TPD in relation to e-cigarettes needs improving so that consumers can access the information which the TPD states they should have access to and to protect young people whose brain development may be adversely affected by consuming nicotine.

  1. New Systems

As restrictive as the TPD is, new products are still being developed. A new type of e-cigarette is emerging onto the market called pods. These devices are small and similar in size to older less effective designs of e-cigarettes (cigalikes) but have the power and nicotine delivery of the newer more effective tank systems. The sleek, compact designs combined with the improved nicotine delivery systems which prevent overheating (which is associated with harmful byproducts such as formaldehyde) are likely to be very popular. These systems can also record information on how the devices are used (how long individuals puff for and how many puffs they take etc.) which could provide essential information to researchers on how e-cigarettes are used in real life situations.

The day culminated in a key note speech by the Attorney General for Iowa, Tom Miller. He commended the UK’s focus on e-cigarette research and the general positive stance our public health officials have taken in terms of e-cigarettes. He concluded his speech by asking for help from the UK to bring the US up to the same standards.

References

  1. PMID: 27650300

Alcohol brief interventions: how can content, provider and setting reduce alcohol consumption?

Posted on by rebeccalawn
by Olivia Maynard @OliviaMaynard17
This blog originally appeared on the Mental Elf site on 23rd September 2016.
screen-shot-2016-09-23-at-10-11-24 

Alcohol brief interventions (ABIs) provide structured advice on alcohol use. They involve an assessment of individual risk with feedback and advice, brief motivational interviewing, or a combination of these techniques.

While the Government’s Alcohol Strategy (HM Government, 2012) recommends that ABIs be implemented increasingly inprimary care settings and accident and emergency (A&E) departments, the National Institute for Health and Care Excellence (NICE) calls for alcohol brief interventions to be offered by a range of practitioners and in a range of different settings.

Given national-level support for increasing and wider use of ABIs, this systematic review and multi-level meta-regression by Platt and colleagues assessed the effectiveness of ABIs on alcohol consumption and how effectiveness of ABIs differs by:

  1. Content of intervention,
  2. Provider group and
  3. Setting.
Alcohol brief interventions usually involve a combination of risk assessment, feedback, advice and brief motivational interviewing.

Alcohol brief interventions usually involve a combination of risk assessment, feedback, advice and brief motivational interviewing.

Methods

Studies were peer-reviewed randomised controlled trials (RCTs) where participants were randomly allocated to a control group (such as treatment as usual) or a group which received an alcohol brief intervention.

Brief interventions were defined as person-to-person discussions on alcohol, with between 1 and 4 sessions and a total of 2 hours intervention time. ABIs which were delivered in groups or via a computer were excluded as were those which included participants with complex health problems where it is difficult to generalise findings to the general population.

The primary outcome measure was a quantitative continuous measure of total alcohol consumption, reported as the standardised mean difference between ABI group and control group measured at follow-up. The authors also examined how ABIs influenced the frequency of alcohol consumption.

Different types of setting, provider and content were examined and these are shown (along with the number of studies in each category) in the Results section below.

A multi-level meta-analysis method was used, which allowed the authors to include a number of different effect sizes from individual studies (i.e. amount of alcohol consumed per unit of time and/or amount of alcohol consumed per drinking occasion) rather than just trying to selecting one comparable effect size for each study).

Results

Study characteristics

50 studies were included in the analyses, with 29,891 individuals contributing data. 45% of studies were conducted in the USA and 22% in the UK.

The percentage of studies which examined alcohol brief interventions with different types of content, providers and settings are shown below:

Intervention content:

  1. Motivational interviewing (MI) (48%)
  2. Enhanced motivational interviewing (MI+) (40%)
  3. Brief advice approaches (24%)

Intervention providers:

  1. Counselors (44%)
  2. General practitioners (22%)
  3. Nurses (18%)
  4. Different providers (12%)
  5. Peer-delivered (4%)

Setting of intervention delivery:

  1. Primary or ambulatory care in clinical settings such as outpatient services (38%)
  2. A&E services (20%)
  3. University (20%)
  4. Community-based delivery (12%)
  5. Hospital inpatient services (10%)

Quality of the evidence

71% of studies were classified as having a low risk of bias regarding randomisation and allocation concealment strategies. However, the method of allocation concealment was unclear in most of the studies. An intention-to-treat analysis was conducted in 47% of the studies and loss to follow-up was assessed in 80% of studies.

The overall impact of ABIs as compared with control conditions

ABIs reduced alcohol consumption by -0.15 SDs (95% confidence interval (CI) = -0.20 to -0.10) a result the authors describe as a ‘small but statistically significant effect’. However, the extent to which this is clinically meaningful is less clear.

Note: The authors present the effect sizes as SDs because they have summarised their data as standardised mean differences. This method is used when included studies all assess the same outcome, but measure it in a variety of ways. Although this makes sense statistically, it does make understanding how important these effects are clinically a little more difficult.

The authors found that this effect persisted after controlling for covariates and when conducting sensitivity analyses. The studies included in this analysis were found to have a small to medium level of heterogeneity (I2 = 37%; this figure is the percentage of variation between trials which is due to actual variation between studies as opposed to variation due to chance. A small I2 value means that the majority of the differences observed between studies was due to chance).

ABIs reduced frequency of alcohol consumed by a similar amount (-0.15 SDs, 95% CI = -0.20 to -0.11).

Content

Splitting studies by ABI content didn’t reduce the heterogeneity between studies (I2 = 39%: no, or little change in this I2 value from when all studies are considered together (I2 = 37%) indicates that this categorisation by content does not adequately explain the heterogeneity between studies).

However, it did appear that all content types were effective at reducing amount of alcohol consumed, and there was some evidence that while brief advice is more effective than MI or MI+ for amount of alcohol consumed, brief advice did not appear to reduce the frequency of consumption while MI and MI+ did.

Providers

Splitting studies by ABI provider was not found to reduce the heterogeneity between studies (I2 = 34%).

ABIs delivered by a range of different providers or by peers were not found to be effective at reducing amount consumed or frequency of consumption (although it’s important to note that very few studies were included in these categories).

There was evidence that interventions delivered by counselors, physicians and nurses were effective, with those delivered by nurses the most effective (-0.23 SDs amount consumed, 95% CI = -0.33 to -0.13).

Setting

Splitting studies by ABI setting didn’t reduce the heterogeneity between studies (I2 = 34%).

There was no evidence that ABIs delivered in hospital inpatient services and in community settings were effective in reducing either amount or frequency of alcohol consumed.

Interventions delivered in A&E, ambulatory care settings and in universities were found to reduce alcohol both amount and frequency of alcohol consumed.

This review suggests that alcohol brief interventions have a ‘small but statistically significant effect’, but it's unclear whether or not this is clinically meaningful.

This review suggests that alcohol brief interventions have a ‘small but statistically significant effect’, but it’s unclear whether or not this is clinically meaningful.

Conclusions

The authors conclude that their study provides:

important new evidence on how the effectiveness of brief alcohol interventions differs by setting, provider and content.

While this analysis does show that ABIs reduce amount of alcohol consumed and frequency of consumption, the size of this effect is small. It will be important to determine to what extent this is a clinically meaningful effect.

Although the authors claim that their findings suggest that the “provider of interventions may matter” (with nurses providing the best results) there is only weak evidence for this. As the categorisation of studies by provider (and setting and content for that matter) didn’t really have any impact on the heterogeneity (as measured by I2) between studies, there is little evidence that the effectiveness of ABIs differed meaningfully across providers.

Interventions delivered by nurses appeared the most effective, although further work is needed to confirm this finding.

Interventions delivered by nurses appeared the most effective, although further work is needed to confirm this finding.

Strengths and limitations

Strengths

As the authors used a multi-level meta-analysis, they were able to include all relevant outcomes into their analysis, rather than just picking one outcome (and consequently having to exclude studies which did not assess this outcome). This is also likely to have reduced study level heterogeneity.

Limitations

As the authors were interested in the difference in effectiveness of a range of different ABI settings, providers and contents, the number of studies included within each of these categories was small. This makes drawing firm conclusions regarding the effectiveness of particular forms of ABIs difficult.

Implications

Given that there is little evidence to suggest that the effectiveness of alcohol brief interventions differs meaningfully according to setting, provider or content, the authors do note that this indicates that resources should be allocated to those settings, providers and contents where ABIs are likely to be most cost-effective and feasible.

For example, A&E may not be the best setting for ABIs given the lack of privacy, the brevity of the visit and the fact that the patient is likely to be suffering from a severe injury at the time.

Nurses are likely to be well placed to provide ABIs given their repeated contact with patients, although appropriate training should be provided to nurses so that they can embed these practices into their care.

Focusing on interventions that are feasible and cost-effective seems like the biggest practical advice from this evidence.

Focusing on interventions that are feasible and cost-effective seems like the biggest practical advice from this evidence.

Links

Primary paper

Platt L, Melendez-Torres GJ, O’Donnell A, Bradley J, Newbury-Birch D, Kaner E, et al. (2016) How effective are brief interventions in reducing alcohol consumption: do the setting, practitioner group and content matter? Findings from a systematic review and metaregression analysis. BMJ Open. 2016;6(8).

Other references

HM Government (2012) The Government’s Alcohol Strategy PDF. CM 8336, March 2012.

Photo credits

Teaming up to improve the Psychology PhD

Posted on by rebeccalawn

by David Troy @DavidTroy79 and Jim Lumsden @jl9937

Human beings are social creatures; we evolved to work together. Our education system is built around this fact; and throughout school and university we encourage students to team up to solve problems, discuss concepts and answer questions. At the same time, as science advances into the 21st century, we find ourselves trying to answer increasingly difficult questions. These new problems cannot be effectively addressed by one person working alone, and academia and industry are increasingly embracing ‘Team Science’, with many articles ssbeing authored by large groups of individuals with a range of specialisms. As experts in disparate fields, these scientists combine their strengths to triangulate evidence and build robust theories. However, in our experience, the field of experimental psychology has yet to adapt to this model of working, and we suspect this has its root at the very beginning of a psychologist’s career: the solo nature of the psychology PhD. This final stage of training to be a scientist consists of a 3-4 year long solo project which, by its very nature, does not foster close collaboration between researchers. A PhD is a course in independent working – it might teach determination, motivation and self-confidence, but it does not teach teamwork. We believe this needs to change.

A new model:

We would like to see a new model of PhD, based on the kind of team environment found in the software development world. Under this model, a research group would be subdivided into several small teams of scientists, with perhaps 3 or 4 PhD students and a postdoc working very closely together. The group would be located in the same office and tackle research questions collaboratively. Overall supervision would come from multiple senior academics, but the post-doc would act as team-leader on a day-to-day basis. Other stakeholders such as clinicians, policy makers and industry-partners may be invited to work within the group to improve the translatability and relevance of the research.

The main purpose of a team-PhD would be to work towards publishable projects much like a conventional company works towards product release deassssdlines or software updates. However, this increased emphasis on publications should not come at the cost of rigour and integrity with the primary focus remaining the adequate training of the candidate in scientific best practice during their PhD. By pooling resources and effort, such a team would be able to tackle the questions addressed by a traditional PhD thesis in less time. Joint 1st authorships would be common, with each team member’s contribution made explicit, rather than recognised implicitly via authorship order. A common theme of research chosen by team members (with direction from the post-doc team leader and supervisors) would be apparent from the team’s output over several years, but the studies and directions chosen should not need to be as cohesive as a traditional PhD. Given that a PhD is supposed to be training there is currently far too much focus on producing a coherent output (the “narrative arc”), rather than developing essential skills (not intending to diminish the important skill of clear, concise scientific writing). We are scientists, not novelists, and should be free to move around various fields to where our skills are needed most.

Let’s imagine a typical working day: You’re busy handling the response letter to the reviewers of your team’s latest paper. Every now and again you turn around to ask your teammates “How should we handle this question? Should we run some extra analysis?”. Your colleague beside you is writing the protocol for your group’s next project. She’s writing in Google Docs, so any member of the team can chip in whenever they want to. The experiment is designed collaboratively, and you will collect the data together. When the data are in, two team members handle the analysis, while the others write the introduction and methods. The team leader allocates different roles on each project, so you’re always learning new skills, but never far from help. Each day starts with a 10-minute meeting, discussing the plan for the day and flagging up any new papers that people have read and any good ideas that have arisen in the last 24 hours.

We believe that working together in a small group would bring many benefits: individuals can read papers and report back summarised findings, they can discuss theories, bounce ideas off each other, cross-check analysis and spot mistakes. Together they can run larger samples, read more widely, attempt more complex analyses, discuss more deeply, and so on. This sort of introspection and group effort leads to rigour, improved quality control, and ultimately higher throughput. Working in a team in this way would be motivating, with more camaraderie and positive peer-pressure, compared to the current PhD experience. Expertise would be shared between team members with the end result being a team of researchers competent in essential scientific skills (e.g., programming, statistics, study design, etc.). A team-PhD would also help to combat the isolation so many postgraduate students feel.

In order to accommodate this change to the nature of the PhD, the existing application process, whereby the candidate prepares a research proposal describing their own project, would need to be replaced with a more general application in which the applicant describes their research skills, areas of interest and motivations for long-term study. Successful applicants would be added to the research team most in need of their skillset: if a team is already strong in statistical methods then perhaps a psychologist could add a new perspective, for example.

A change in the PhD structure would also require a change to the assessment process. It is often said that PhD theses ends up in university libraries, never to be read again. Given that PhDs are often publically funded, the time spent altering a publication to fit the narrative arc of a thesis would be better spent dedicated to science that can have tangible impact. University of Bristol, alongside other universities, offers an alternative, if rarely used, PhD by published work. In this format candidates do not submit a thesis, but rather must publish a series of “coherent” works, alongside a commentary on the general direction of their research, its scope and aims. Currently, it takes ~10 years to amass enough publications to qualify for this route; however, it is plausible to alter this to the timeframe of a normal PhD. This format of PhD is more likely to produce high quality scientific output, published in academic journals, rather than rotting on a library shelf. Additionally, a PhD-by-publication still requires an oral examination. This exam would be used to ensure that team-PhD candidates are still capable, independent scientists with a sound understanding of their field, even though the bulk of their research was conducted as part of a team.

The teaming up of researchers with different competencies working on publications may have unintended consequences. It may be difficult to find one person to adequately review such work as is currently the case in neurogenetics for example. A possible remedy would be to restructure the review process to include teams of reviewers, where each member of the team specialises in addressing one of the specialisms described in the paper.ssssssssss

So, how can we move from solo training to team-based training? We suggest it is possible to trial the addition of team science to the PhD process by mandating that new PhD candidates work in a team, as part of their 1st year of study. In recent years, the 1+3 year PhD has become more common, whereby candidates carry out solo mini-projects in their 1st year to acquire experience and training in disparate fields. This could be altered to incorporate close teamwork in the execution of these mini-projects. This would provide an opportunity to examine the everyday benefits and challenges of this new mode of working. This way, students would not be overly disadvantaged when emerging from their PhD into a world of academia still concentrated around the principal investigator model, as the majority of their training would still be focused on generating and implementing their own ideas and developing their own “brand” or intellectual identity as a scientist.

Conclusion

The current model of attaining a PhD in psychology is too focused on solo work. We argue that introducing a more collaborative and cohesive framework to the PhD would aid in the development of research skills and produce more well-rounded PhD graduates equipped to tackle complex research questions. We hope this blog post will spark debate about the suitability of current training for psychological research and generate further ideas on how it can be improved to produce researchers with the skillset necessary for science in the 21st century.

 

Photo credits:

  1. http://dk.hjernekraft.org/turnering/279/lillestrom/lag.aspx?id=5602
  2. https://fbs.admin.utah.edu/research-corner/2015/07/28/enhancing-the-effectiveness-of-team-science/
  3. http://deevybee.blogspot.co.uk/2016/10/on-incomprehensibility-of-much.html