Defining and conceptualising the commercial determinants of health.

Although commercial entities can contribute positively to health and society there is growing evidence that the products and practices of some commercial actors-notably the largest transnational corporations-are responsible for escalating rates of avoidable ill health, planetary damage, and social and health inequity; these problems are increasingly referred to as the commercial determinants of health. The climate emergency, the non-communicable disease epidemic, and that just four industry sectors (ie, tobacco, ultra-processed food, fossil fuel, and alcohol) already account for at least a third of global deaths illustrate the scale and huge economic cost of the problem. This paper, the first in a Series on the commercial determinants of health, explains how the shift towards market fundamentalism and increasingly powerful transnational corporations has created a pathological system in which commercial actors are increasingly enabled to cause harm and externalise the costs of doing so. Consequently, as harms to human and planetary health increase, commercial sector wealth and power increase, whereas the countervailing forces having to meet these costs (notably individuals, governments, and civil society organisations) become correspondingly impoverished and disempowered or captured by commercial interests. This power imbalance leads to policy inertia; although many policy solutions are available, they are not being implemented. Health harms are escalating, leaving health-care systems increasingly unable to cope. Governments can and must act to improve, rather than continue to threaten, the wellbeing of future generations, development, and economic growth.

Early pharmacological interventions for prevention of post-traumatic stress disorder (PTSD) in individuals experiencing acute traumatic stress symptoms.

BACKGROUND: Acute traumatic stress symptoms may develop in people who have been exposed to a traumatic event. Although they are usually self-limiting in time, some people develop post-traumatic stress disorder (PTSD), a severe and debilitating condition. Pharmacological interventions have been proposed for acute symptoms to act as an indicated prevention measure for PTSD development. As many individuals will spontaneously remit, these interventions should balance efficacy and tolerability. OBJECTIVES: To assess the efficacy and acceptability of early pharmacological interventions for prevention of PTSD in adults experiencing acute traumatic stress symptoms. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trial Register (CCMDCTR), CENTRAL, MEDLINE, Embase and two other databases. We checked the reference lists of all included studies and relevant systematic reviews. The search was last updated on 23 January 2023. SELECTION CRITERIA: We included randomised controlled trials on adults exposed to any kind of traumatic event and presenting acute traumatic stress symptoms, without restriction on their severity. We considered comparisons of any medication with placebo, or with another medication. We excluded trials that investigated medications as an augmentation to psychotherapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Using a random-effects model, we analysed dichotomous data as risk ratios (RR) and calculated the number needed to treat for an additional beneficial/harmful outcome (NNTB/NNTH). We analysed continuous data as mean differences (MD) or standardised mean differences (SMD). Our primary outcomes were PTSD severity and dropouts due to adverse events. Secondary outcomes included PTSD rate, functional disability and quality of life. MAIN RESULTS: We included eight studies that considered four interventions (escitalopram, hydrocortisone, intranasal oxytocin, temazepam) and involved a total of 779 participants. The largest trial contributed 353 participants and the next largest, 120 and 118 participants respectively. The trials enrolled participants admitted to trauma centres or emergency departments. The risk of bias in the included studies was generally low except for attrition rate, which we rated as high-risk. We could meta-analyse data for two comparisons: escitalopram versus placebo (but limited to secondary outcomes) and hydrocortisone versus placebo. One study compared escitalopram to placebo at our primary time point of three months after the traumatic event. There was inconclusive evidence of any difference in terms of PTSD severity (mean difference (MD) on the Clinician-Administered PTSD Scale (CAPS, score range 0 to 136) -11.35, 95% confidence interval (CI) -24.56 to 1.86; 1 study, 23 participants; very low-certainty evidence), dropouts due to adverse events (no participant left the study early due to adverse events; 1 study, 31 participants; very low-certainty evidence) and PTSD rates (RR 0.59, 95% CI 0.03 to 13.08; NNTB 37, 95% CI NNTB 15 to NNTH 1; 1 study, 23 participants; very low-certainty evidence). The study did not assess functional disability or quality of life. Three studies compared hydrocortisone to placebo at our primary time point of three months after the traumatic event. We found inconclusive evidence on whether hydrocortisone was more effective in reducing the severity of PTSD symptoms compared to placebo (MD on CAPS -7.53, 95% CI -25.20 to 10.13; I2 = 85%; 3 studies, 136 participants; very low-certainty evidence) and whether it reduced the risk of developing PTSD (RR 0.47, 95% CI 0.09 to 2.38; NNTB 14, 95% CI NNTB 8 to NNTH 5; I2 = 36%; 3 studies, 136 participants; very low-certainty evidence). Evidence on the risk of dropping out due to adverse events is inconclusive (RR 3.19, 95% CI 0.13 to 75.43; 2 studies, 182 participants; low-certainty evidence) and it is unclear whether hydrocortisone might improve quality of life (MD on the SF-36 (score range 0 to 136, higher is better) 19.70, 95% CI -1.10 to 40.50; 1 study, 43 participants; very low-certainty evidence). No study assessed functional disability. AUTHORS' CONCLUSIONS: This review provides uncertain evidence regarding the use of escitalopram, hydrocortisone, intranasal oxytocin and temazepam for people with acute stress symptoms. It is therefore unclear whether these pharmacological interventions exert a positive or negative effect in this population. It is important to note that acute traumatic stress symptoms are often limited in time, and that the lack of data prevents the careful assessment of expected benefits against side effects that is therefore required. To yield stronger conclusions regarding both positive and negative outcomes, larger sample sizes are required. A common operational framework of criteria for inclusion and baseline assessment might help in better understanding who, if anyone, benefits from an intervention. As symptom severity alone does not provide the full picture of the impact of exposure to trauma, assessment of quality of life and functional impairment would provide a more comprehensive picture of the effects of the interventions. The assessment and reporting of side effects may facilitate a more comprehensive understanding of tolerability.

Cognitive behavioural therapy and third-wave approaches for anxiety and related disorders in older people.

BACKGROUND: Cognitive behavioural therapy (CBT) is the most researched psychological therapy for anxiety disorders in adults, and known to be effective in this population. However, it remains unclear whether these results apply to older adults, as most studies include participants between 18 and 55 years of age. This systematic review aims to provide a comprehensive and up-to-date synthesis of the available evidence on CBT and third wave approaches for older adults with anxiety and related disorders. OBJECTIVES: To assess the effects of Cognitive Behavioural Therapy (CT, BT, CBT and third-wave CBT interventions) on severity of anxiety symptoms compared with minimal management (not providing therapy) for anxiety and related disorders in older adults, aged 55 years or over. To assess the effects of CBT and related therapies on severity of anxiety symptoms compared with other psychological therapies for anxiety and related disorders in older adults, aged 55 years or over. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled studies Register (CCMDCTR), CENTRAL, Ovid MEDLINE, Ovid Embase and Ovid PsycINFO to 21 July 2022. These searches were updated on 2 February 2024. We also searched the international studies registries, including Clinicalstudies.gov and the WHO International Clinical Trials Registry Platform (ICTRP), to identify additional ongoing and unpublished studies. These sources were manually searched for studies up to 12 February 2024. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in older adults (≥ 55 years) with an anxiety disorder, or a related disorder, including obsessive compulsive disorder (OCD), acute stress disorder and post-traumatic stress disorder (PTSD), that compared CBT to either minimal management or an active (non-CBT) psychological therapy. Eligible studies had to have an anxiety-related outcome. DATA COLLECTION AND ANALYSIS: Several authors independently screened all titles identified by the searches. All full texts were screened for eligibility according to our prespecified selection criteria. Data were extracted and the risk of bias was assessed using the Cochrane tool for RCTs. The certainty of evidence was evaluated using GRADE. Meta-analyses were performed for outcomes with quantitative data from more than one study. MAIN RESULTS: We included 21 RCTs on 1234 older people allocated to either CBT or control conditions. Ten studies focused on generalised anxiety disorder; others mostly included a mix of clinical diagnoses. Nineteen studies focused on the comparison between CBT and minimal management. Key issues relating to risk of bias were lack of blinding of participants and personnel, and participants dropping out of studies, potentially due to treatment preference and allocation. CBT may result in a small-to-moderate reduction of anxiety post-treatment (SMD -0.51, 95% CI -0.66 to -0.36, low-certainty evidence). However, compared to this benefit with CBT immediately after treatment, at three to six months post-treatment, there was little to no difference between CBT and minimal management (SMD -0.29, 95% CI -0.59 to 0.01, low-certainty evidence). CBT may have little or no effect on clinical recovery/ improvement post-treatment compared to minimal management, but the evidence is very uncertain (RR 1.56, 95% CI 1.20 to 2.03, very low-certainty evidence). Results indicate that five people would need to receive treatment for one additional person to benefit (NNTB = 5). Compared to minimal management, CBT may result in a reduction of comorbid depression symptoms post-treatment (SMD -0.57, 95% CI -0.74 to -0.40, low-certainty evidence). There was no difference in dropout rates post-treatment, although the certainty of the evidence was low (RR 1.19, 95% CI 0.80 to 1.78). Two studies reported adverse events, both of which related to medication in the control groups (very low-certainty evidence, no quantitative estimate). Only two studies compared CBT to other psychological therapies, both of which only included participants with post-traumatic stress disorder. Low-certainty evidence showed no difference in anxiety severity post-treatment and at four to six months post-treatment, symptoms of depression post-treatment, and dropout rates post-treatment. Other outcomes and time points are reported in the results section of the manuscript. AUTHORS' CONCLUSIONS: CBT may be more effective than minimal management in reducing anxiety and symptoms of worry and depression post-treatment in older adults with anxiety disorders. The evidence is less certain longer-term and for other outcomes including clinical recovery/improvement. There is not enough evidence to determine whether CBT is more effective than alternative psychological therapies for anxiety in older adults.

A Qualitative Analysis of the Experiences of People Who Resumed Smoking Following Exclusive Electronic Nicotine Delivery Systems Use.

INTRODUCTION: For electronic nicotine delivery systems (ENDS) to reduce harms caused by smoking, people who smoke must be able to switch to exclusive ENDS use without subsequently returning to smoking. Identifying factors prompting a return to smoking among former exclusive ENDS users is crucial, yet few qualitative studies have probed experiences of this process. AIMS AND METHODS: We conducted in-depth, semi-structured interviews with 20 people (seven indigenous Maori and 13 non-Maori) who smoked tobacco at least weekly, had smoked at least 100 cigarettes in their lifetime, and reported using ENDS to stop smoking cigarettes for at least 30 days (ideally, within the preceding 6 months). We explored their experiences of ENDS use, probed critical return-to-smoking settings and triggers, and analyzed strategies that could promote sustained smoking abstinence. We managed data using NVivo12 and used a reflexive thematic analysis approach to interpret the transcripts. RESULTS: We identified three themes that explained participants' experiences. ENDS performed a functional role by mimicking some aspects of smoking. Yet participants experienced ENDS as inauthentic and unsatisfying across physical, social, and affectual domains, including in the most common return-to-smoking situations. Furthermore, fewer constraints on ENDS usage led participants to feel they could perpetuate addiction and risk of harm. CONCLUSIONS: Return to smoking reflected two factors: ENDS' failure to replicate core smoking attributes that remained appealing, and the burden of self-regulation required when using ENDS. Understanding and informing people about the challenges involved in transitioning to ENDS, beyond obtaining sufficient nicotine, could help support informed ENDS use and may potentially prevent people returning to smoking. IMPLICATIONS: Our study extends our understanding of the satisfaction people seek when attempting to transition from smoking to exclusive ENDS use, and how ENDS' failure to replicate that satisfaction, in addition to uncertainty about ENDS-related risks, contributes to smoking resumption. Satisfaction went beyond nicotine delivery, and included affective experiences, maintenance of rituals, rewards, and social connections. Conceptualizing satisfaction more broadly could support a richer understanding of factors that prompt return to smoking. People might manage challenges more effectively if they understood these before attempting to switch from smoking to ENDS, and if they are advised to monitor and regulate their ENDS use. Educational resources and behavioral support could provide more guidance on these points.

An Analysis of Arguments Advanced via Twitter in an Advocacy Campaign to Promote Electronic Nicotine Delivery Systems.

INTRODUCTION: Advocates of electronic nicotine delivery systems (ENDS) increasingly use Twitter to promote liberal ENDS policies. "World Vape Day" (WVD) is an annual campaign organized by pro-ENDS advocacy groups, some of which have links to the nicotine industry (eg, via funding from the "Foundation for a Smoke-Free World"). In 2020, the campaign used dedicated social media accounts to disseminate WVD-branded images and campaign messages. We examined tweets posted as part of WVD 2020 to identify and analyze pro-ENDS policy arguments. AIMS AND METHODS: We extracted tweets posted between 26 May and 3 June 2020 that included the hashtag #WorldVapeDay. We used qualitative thematic analysis to code a random sample (n = 2200) of approximately half the original English language tweets (n = 4387) and used descriptive analysis to identify the most frequently used co-hashtags. RESULTS: Arguments related to four themes: harm reduction, smoking cessation, rights and justice, and opposition to ENDS restrictions. Tweets criticized individuals and groups perceived as opposing liberal ENDS regulation, and used personal testimonials to frame ENDS as a harm reduction tool and life-saving smoking cessation aid. Tweets also advanced rights-based arguments, such as privileging adults' rights over children's rights, and calling for greater recognition of consumers' voices. Tweets frequently used hashtags associated with the WHO and World No Tobacco Day (WNTD). CONCLUSIONS: The WVD campaign presented a series of linked pro-ENDS arguments seemingly aimed at policy-makers, and strategically integrated with the WHO's WNTD campaign. Critically assessing pro-ENDS arguments and the campaigns used to promote these is vital to helping policy actors develop proportionate ENDS policy. IMPLICATIONS: Social media platforms have considerable potential to influence policy actors. Tweets are easily generated and duplicated, creating an impression of sizeable and influential stakeholders. Evidence that the "World Vape Day" campaign was supported by groups with industry links, and targeted-at least in part-at WHO officials and those who follow the WHO World No Tobacco Day campaign, highlights the importance of critically reviewing such campaigns. Further research could examine how health advocates could engage in pro-ENDS campaigns to support balanced messaging and informed policy-making.

Ethics and ENDS.

As debate persists over regulating electronic nicotine delivery systems (ENDS), those favouring liberal ENDS policies have advanced rights-based arguments privileging harm reduction to people who smoke over harm prevention to children and never-smokers. Recent ethical arguments advocate regulating ENDS to prioritise their harm reduction potential for people who currently smoke over any future harm to young never-smokers. In this article, we critically assess these arguments, in particular, the assumption that ethical arguments for prioritising the interests of young people do not apply to ENDS. We argue that, when the appropriate comparators are used, it is not clear the weight of ethical argument tips in favour of those who currently smoke and against young never-smokers. We also assert that arguments from a resource prioritisation context are not appropriate for analysing ENDS regulation, because ENDS are not a scarce resource. Further, we reject utilitarian arguments regarding maximising net population health benefits, as these do not adequately consider vulnerable groups' rights, or address the population distribution of benefits and harms. Lastly, we argue that one-directional considerations of harm reduction do not recognise that ENDS potentially increase harm to those who do not smoke and who would not otherwise have initiated nicotine use.

Framing the policy debate over tobacco control legislation and tobacco taxation in South Africa.

BACKGROUND: In 2018, South Africa opened public consultations on its newly proposed tobacco control bill, resulting in substantial public debate in which a range of arguments, either in favour of or against the Bill, was advanced. These were accompanied by the recurring discussions about the annual adjustments in tobacco taxation. This study uses the concept of framing to examine the public debate in South African print media on the potential effects of the legislation, as well as tobacco tax regulations, between their proponents and detractors. METHODS: A systematic search of news articles using multiple data sources identified 132 media articles published between January 2018 and September 2019 that met the inclusion criteria. RESULTS: Seven overarching frames were identified as characterising the media debate, with the three dominant frames being Economic, Harm reduction and vaping, and Health. The leading Economic frame consisted primarily of arguments unsupportive of tobacco control legislation. Economic arguments were promoted by tobacco industry spokespeople, trade unions, organisations of retailers, media celebrities and think tanks-several of which have been identified as front groups or third-party lobbyists for the tobacco industry. CONCLUSION: The dominance of economic arguments opposing tobacco control legislation risks undermining tobacco control progress. Local and global tobacco control advocates should seek to build relationships with media, as well as collate and disseminate effective counterarguments to those advanced by the industry.

Mental Health First Aid as a tool for improving mental health and well-being.

BACKGROUND: The prevalence of mental health problems is high, and they have a wide-ranging and deleterious effect on many sectors in society. As well as the impact on individuals and families, mental health problems in the workplace negatively affect productivity. One of the factors that may exacerbate the impact of mental health problems is a lack of 'mental health literacy' in the general population. This has been defined as 'knowledge and beliefs about mental disorders, which aid their recognition, management, or prevention'. Mental Health First Aid (MHFA) is a brief training programme developed in Australia in 2000; its aim is to improve mental health literacy and teach mental health first aid strategies. The course has been adapted for various contexts, but essentially covers the symptoms of various mental health disorders, along with associated mental health crisis situations. The programmes also teach trainees how to provide immediate help to people experiencing mental health difficulties, as well as how to signpost to professional services. It is theorised that improved knowledge will encourage the trainees to provide support, and encourage people to actively seek help, thereby leading to improvements in mental health. This review focuses on the effects of MHFA on the mental health and mental well-being of individuals and communities in which MHFA training has been provided. We also examine the impact on mental health literacy. This information is essential for decision-makers considering the role of MHFA training in their organisations. OBJECTIVES: To examine mental health and well-being, mental health service usage, and adverse effects of MHFA training on individuals in the communities in which MHFA training is delivered. SEARCH METHODS: We developed a sensitive search strategy to identify randomised controlled trials (RCTs) of MHFA training. This approach used bibliographic databases searching, using a search strategy developed for Ovid MEDLINE (1946 -), and translated across to Ovid Embase (1974 -), Ovid PsycINFO (1967 -), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Common Mental Disorders Group's Specialised Register (CCMDCTR). We also searched online clinical trial registries (ClinicalTrials.gov and WHO ICTRP), grey literature and reference lists of included studies, and contacted researchers in the field to identify additional and ongoing studies. Searches are current to 13th June 2023. SELECTION CRITERIA: We included RCTs and cluster-RCTs comparing any type of MHFA-trademarked course to no intervention, active or attention control (such as first aid courses), waiting list control, or alternative mental health literacy interventions. Participants were individuals in the communities in which MHFA training is delivered and MHFA trainees. Primary outcomes included mental health and well-being of individuals, mental health service usage and adverse effects of MHFA training. Secondary outcomes related to individuals, MHFA trainees, and communities or organisations in which MHFA training has been delivered DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We analysed categorical outcomes as risk ratios (RRs) and odds ratios (ORs), and continuous outcomes as mean differences (MDs) or standardised mean differences (SMDs), with 95% confidence intervals (CIs). We pooled data using a random-effects model. Two review authors independently assessed the key results using the Risk of Bias 2 tool and applied the GRADE criteria to assess the certainty of evidence MAIN RESULTS: Twenty-one studies involving a total of 22,604 participants were included in the review. Fifteen studies compared MHFA training with no intervention/waiting list, two studies compared MHFA training with an alternative mental health literacy intervention, and four studies compared MHFA training with an active or an attention control intervention. Our primary time point was between six and 12 months. When MHFA training was compared with no intervention, it may have little to no effect on the mental health of individuals at six to 12 months, but the evidence is very uncertain (OR 0.88, 95% CI 0.61 to 1.28; 3 studies; 3939 participants). We judged all the results that contributed to this outcome as being at high risk of bias. No study measured mental health service usage at six to 12 months. We did not find published data on adverse effects. Only one study with usable data compared MHFA training with an alternative mental health literacy intervention. The study did not measure outcomes in individuals in the community. It also did not measure outcomes at our primary time point of six to 12 months. Four studies with usable data compared MHFA training to an active or attention control. None of the studies measured outcomes at our primary time point of six to 12 months. AUTHORS' CONCLUSIONS: We cannot draw conclusions about the effects of MHFA training on our primary outcomes due to the lack of good quality evidence. This is the case whether it is compared to no intervention, to an alternative mental health literacy intervention, or to an active control. Studies are at high risk of bias and often not sufficiently large to be able to detect differences.

Pharmacological treatments in panic disorder in adults: a network meta-analysis.

BACKGROUND: A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines. OBJECTIVES: To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses. MAIN RESULTS: Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low. AUTHORS' CONCLUSIONS: In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.

The in vitro biomechanics of anterior arch expansion using fixed lingual appliances with coil springs or archwire stops.

INTRODUCTION: The presented study investigates differences in the biomechanics of straight and mushroom fixed lingual appliances when implementing coil springs and stops for anterior arch expansion. MATERIALS AND METHODS: An in vitro orthodontic simulator was used to measure three-dimensional forces and moments on each tooth of a simulated maxillary arch. Mushroom and straight archwire forms of 0.016″ NiTi round archwire were considered, using 0.010″ × 0.030″ NiTi open coils and 0.016″-0.018″ archwire stops (n = 44 per group). Teeth in the anterior dental arch were moved from a neutral to crowded position to replicate anterior crowding of central and lateral incisors. Forces and moments of interest for lateral incisors and first premolars were compared using repeated measures mixed multivariate analysis of variance (α = 0.05). RESULTS: Three comparisons between straight versus mushroom archwires and two comparisons of coil springs vs. stops were not statistically significant. Overall, it was found that the use of a straight lingual archwire produced larger differences in forces and moments between using stops and coil springs than when using a mushroom archwire. Using stops produced larger forces and moments for both types of archwires as compared to using coil springs. The largest expansion forces were produced using straight archwires with stops, exceeding 3.0 N of force. Straight archwires with coil springs produced the lowest expansion forces on lateral incisors, just exceeding 1.5 N. CONCLUSIONS: The findings of this study have elucidated significant differences in the biomechanics of transverse arch expansion using straight or mushroom fixed lingual appliances with coil springs or stops.

Exploring the Twitter activity around the eighth meeting of the Conference of the Parties to the WHO Framework Convention on Tobacco Control.

BACKGROUND: Tobacco companies' intentions to influence the WHO Framework Convention on Tobacco Control (FCTC) via the Conference of Parties (COP; the official biannual meeting where Parties review the Convention) are well documented. We aimed to analyse Twitter data to gain insights into tobacco industry tactics, arguments and allies. METHODS: We retrieved 9089 tweets that included #COP8FCTC between 1 and 9 October 2018. We categorised the tweets' content and sentiment through manual coding and machine learning. We used an investigative procedure using publicly available information to categorise the most active Twitter users and investigate tobacco industry links. Network analysis was used to visualise interactions and detect communities. RESULTS: Most tweets were about next-generation products (NGPs) or 'harm reduction' (54%) and tended to argue in support of NGPs; around one-quarter were critical of tobacco control (24%). The largest proportion of most active tweeters were NGP advocates, and slightly over half of those had either links to the Philip Morris International (PMI) funded Foundation for a Smoke-Free World (FSFW) and/or to the International Network of Nicotine Consumer Organisations, a network to whom the FSFW granted US$100 300 in 2018. PMI was the most active transnational tobacco company during COP8. CONCLUSIONS: The nature of the activity on Twitter around COP8, including a substantial online presence by PMI executives and NGP advocates with links to organisations funded directly and indirectly by PMI, is highly consistent with PMI's 2014 corporate affairs strategy, which described engaging tobacco harm reduction advocates to 'amplify and leverage the debate on harm reduction' around events such as the COP.

Is the tobacco 'footfall' argument justified for tobacco purchases in New Zealand convenience stores?

INTRODUCTION: New Zealand's Smokefree 2025 goal aims to greatly decrease the availability of tobacco. One option is to cease the sale of tobacco from convenience stores. However, tobacco companies and retail trade associations oppose this move and have argued that customers who purchase tobacco drive footfall and spend more than non-tobacco customers. The aim of this study is to test the validity of industry claims about the importance of tobacco to convenience stores. METHODS: During November and December 2019, immediate postpurchase surveys were undertaken with customers on exit from a random sample of 100 convenience stores in two New Zealand cities. We estimated the mean number of items purchased, including tobacco and non-tobacco items, and mean expenditure on non-tobacco items. RESULTS: Of the 3399 transactions recorded, 13.8% included tobacco, of which 8.3% comprised tobacco only and 5.5% included tobacco and non-tobacco items. The mean number of transactions containing both tobacco and non-tobacco items was 1.98, and 1.87 for those containing non-tobacco items only. Customers who purchased tobacco and non-tobacco items spent on average NZ$6.99 on non-tobacco items, whereas customers who purchased non-tobacco items only, spent on average NZ$5.07. CONCLUSIONS: Our results do not support claims that tobacco drives one-quarter of footfall into stores or that customers who purchase tobacco spend almost twice as much as non-tobacco customers. Combined purchases of tobacco and non-tobacco items constituted 5.5% of transactions; the impact on a store's profitability of removing tobacco sales is unknown and could be the focus of future research.

Early pharmacological interventions for universal prevention of post-traumatic stress disorder (PTSD).

BACKGROUND: Post-traumatic stress disorder (PTSD) is a severe and debilitating condition. Several pharmacological interventions have been proposed with the aim to prevent or mitigate it. These interventions should balance efficacy and tolerability, given that not all individuals exposed to a traumatic event will develop PTSD. There are different possible approaches to preventing PTSD; universal prevention is aimed at individuals at risk of developing PTSD on the basis of having been exposed to a traumatic event, irrespective of whether they are showing signs of psychological difficulties. OBJECTIVES: To assess the efficacy and acceptability of pharmacological interventions for universal prevention of PTSD in adults exposed to a traumatic event. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trial Register (CCMDCTR), CENTRAL, MEDLINE, Embase, two other databases and two trials registers (November 2020). We checked the reference lists of all included studies and relevant systematic reviews. The search was last updated on 13 November 2020. SELECTION CRITERIA: We included randomised clinical trials on adults exposed to any kind of traumatic event. We considered comparisons of any medication with placebo or with another medication. We excluded trials that investigated medications as an augmentation to psychotherapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. In a random-effects model, we analysed dichotomous data as risk ratios (RR) and number needed to treat for an additional beneficial/harmful outcome (NNTB/NNTH). We analysed continuous data as mean differences (MD) or standardised mean differences (SMD). MAIN RESULTS: We included 13 studies which considered eight interventions (hydrocortisone, propranolol, dexamethasone, omega-3 fatty acids, gabapentin, paroxetine, PulmoCare enteral formula, Oxepa enteral formula and 5-hydroxytryptophan) and involved 2023 participants, with a single trial contributing 1244 participants. Eight studies enrolled participants from emergency departments or trauma centres or similar settings. Participants were exposed to a range of both intentional and unintentional traumatic events. Five studies considered participants in the context of intensive care units with traumatic events consisting of severe physical illness. Our concerns about risk of bias in the included studies were mostly due to high attrition and possible selective reporting. We could meta-analyse data for two comparisons: hydrocortisone versus placebo, but limited to secondary outcomes; and propranolol versus placebo. No study compared hydrocortisone to placebo at the primary endpoint of three months after the traumatic event. The evidence on whether propranolol was more effective in reducing the severity of PTSD symptoms compared to placebo at three months after the traumatic event is inconclusive, because of serious risk of bias amongst the included studies, serious inconsistency amongst the studies' results, and very serious imprecision of the estimate of effect (SMD -0.51, 95% confidence interval (CI) -1.61 to 0.59; I2 = 83%; 3 studies, 86 participants; very low-certainty evidence). No study provided data on dropout rates due to side effects at three months post-traumatic event. The evidence on whether propranolol was more effective than placebo in reducing the probability of experiencing PTSD at three months after the traumatic event is inconclusive, because of serious risk of bias amongst the included studies, and very serious imprecision of the estimate of effect (RR 0.77, 95% CI 0.31 to 1.92; 3 studies, 88 participants; very low-certainty evidence). No study assessed functional disability or quality of life.  Only one study compared gabapentin to placebo at the primary endpoint of three months after the traumatic event, with inconclusive evidence in terms of both PTSD severity and probability of experiencing PTSD, because of imprecision of the effect estimate, serious risk of bias and serious imprecision (very low-certainty evidence). We found no data on dropout rates due to side effects, functional disability or quality of life. For the remaining comparisons, the available data are inconclusive or missing in terms of PTSD severity reduction and dropout rates due to adverse events. No study assessed functional disability. AUTHORS' CONCLUSIONS: This review provides uncertain evidence only regarding the use of hydrocortisone, propranolol, dexamethasone, omega-3 fatty acids, gabapentin, paroxetine, PulmoCare formula, Oxepa formula, or 5-hydroxytryptophan as universal PTSD prevention strategies. Future research might benefit from larger samples, better reporting of side effects and inclusion of quality of life and functioning measures.

A Qualitative Analysis of Maori and Pacific people's Experiences of Using Electronic Nicotine Delivery Systems (ENDS).

INTRODUCTION: If electronic nicotine delivery systems (ENDS) are to bring public health benefits, members of population groups most affected by smoking must find them an easily adopted and satisfying replacement for smoking. We explored experiences of ENDS uptake and use among Maori and Pacific peoples living in New Zealand and probed factors that assisted transitions from smoking to vaping. METHODS: We recruited 16 participants using whanaungatanga and community advertising. All were aged 18 or over, identified as Maori or Pacific (or both), had smoked at least 100 cigarettes, and were current ENDS users. We undertook in-depth interviews and analyzed the data using a thematic analysis approach. RESULTS: We identified two key challenges that participants reported facing: their search for a satisfying ENDS experience and resisting social cues that could trigger relapse. Two supportive factors facilitated and reinforced smoking to vaping transitions: improved financial and physical well-being, and feeling connected to vaping communities. CONCLUSION: Learning about ENDS devices from those who had successfully switched from smoking to vaping provided much-needed information, reinforced the financial benefits of switching, and could inspire those making this transition to persist until they too become smoke free. IMPLICATIONS: Measures to support transitions from smoking to ENDS use could reduce inequities in smoking prevalence that indigenous people experience. Collective cessation interventions that draw on communities' knowledge and connections may enable smokers to access support that helps them navigate the potentially complex pathway from smoking to vaping.

It's Just Steam: a qualitative analysis of New Zealand ENDS users' perceptions of secondhand aerosol.

INTRODUCTION: Many smokers who begin using electronic nicotine delivery systems (ENDS) report vaping in settings where they would not have smoked and believe secondhand aerosol (SHA) is simply steam. However, current understanding of how ENDS users differentiate between secondhand smoke and SHA, or how vaping norms develop, is limited. METHODS: We conducted in-depth, semi-structured interviews with 39 current ENDS users (dual users and former smokers, now exclusive ENDS users) from New Zealand to explore participants' perceptions of SHA. We probed how these perceptions arose and examined implications for vaping practices and policy. We managed the data using NVivo V.11 and used a thematic analysis approach to interpret the transcripts. RESULTS: Participants had limited understanding of SHA, its constituents or its possible effects on others. They drew on the absence of harm information, and their sensory experiences and perceptions of others' views of vaping, to support the conclusion that SHA posed few, if any, risks to bystanders. Yet despite this perception, some felt they should recognise others' rights to clean air and most would not vape around children to avoid setting an example. CONCLUSIONS: In the absence of trusted information, participants used sensory heuristics to rationalise their ENDS practices. Policy-makers face the challenge of correcting misperceptions about SHA without deterring full transition from smoking to ENDS use. They could consider including vaping in current smoke-free area policies; this measure would signal that SHA is not harmless, and could protect clean-air settings and reduce potential normalisation of vaping among non-smokers.

Graduated compression stockings for the initial treatment of varicose veins in people without venous ulceration.

BACKGROUND: Compression hosiery or stockings are often the first line of treatment for varicose veins in people without either healed or active venous ulceration. Evidence is required to determine whether the use of compression stockings can effectively manage and treat varicose veins in the early stages. This is the second update of a review first published in 2011. OBJECTIVES: To assess the effectiveness of compression stockings for the only and initial treatment of varicose veins in people without healed or active venous ulceration. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and AMED databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 12 May 2020. We also checked references of studies identified from the literature searches. SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving people diagnosed with primary trunk varicose veins without healed or active venous ulceration (Clinical, Etiology, Anatomy, Pathophysiology (CEAP) classification C2 to C4). Included trials assessed compression stockings versus no treatment or placebo stockings, or compression stockings plus drug intervention versus drug intervention alone. We also included trials comparing different lengths and pressures of stockings. We excluded trials involving other types of treatment for varicose veins (either as a comparator to stockings or as an initial non-randomised treatment), including sclerotherapy and surgery. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. Two review authors independently assessed trials for inclusion, extracted data, assessed risk of bias and assessed the certainty of the evidence using GRADE. Outcomes of interest were change in symptoms; physiological measures; complications; compliance; comfort, tolerance and acceptability of wearing stockings; and quality of life. MAIN RESULTS: We included 13 studies with 1021 participants with varicose veins without healed or active venous ulceration. One study included pregnant women while other studies included participants who had sought medical intervention for their varicose veins by being on surgical waiting lists, or attending vascular surgery or dermatology clinics or outpatient departments. The stockings used in the studies exerted different levels of pressure, ranging from 10 mmHg to 50 mmHg. Five studies assessed compression stockings versus no compression stockings or placebo stockings. Three of these studies used knee-length stockings, one used full-length stockings and one used full tights. Eight studies compared different types or pressures of knee-length stockings. The risk of bias of many included trials was unclear, mainly because of inadequate reporting. We were unable to pool studies as they did not report the same outcomes or used different ways to assess them. Many studies were small and there were differences in the populations studied. The certainty of the evidence was therefore low to very low. Compression stockings compared with no treatment or placebo stockings All four studies that reported change in symptoms found a subjective improvement by the end of the study. However, change in symptoms was not always analysed by comparing the randomised arms of the studies and was therefore subject to bias. Two studies assessed physiological measures using either ankle circumference or duplex sonography to measure oedema. Ankle circumference showed no clear difference between baseline and follow-up while oedema was reduced in the stocking group compared with the placebo stocking group. Three studies reported complications or side effects with itching and irritation the main side effects reported. None of the trials reported severe side effects. Reports of compliance varied between studies. One study reported a high dropout rate with low levels of compliance due to discomfort, application and appearance; two studies reported generally good levels of compliance in the stocking group compared to placebo/no treatment. Two studies reported comfort, tolerance and acceptability with outcomes affected by the study population. Compression tights were increasingly rejected by pregnant women as their pregnancy progressed, while in one study of non-pregnant women, the stockings group showed no more hindrance of normal activities and daytime discomfort when compared with placebo stockings. One study reported quality of life showing no clear differences between the stocking and placebo stocking groups. Compression stockings compared with different compression stockings All five studies that reported change in symptoms found a subjective improvement in symptoms by the end of the study. Change in symptoms was not always analysed comparing the randomised arms of the trials and was therefore subject to bias. Five studies reported a variety of physiological measures such as foot volumetry, volume reduction and change in diameter. Generally, there were no clear differences between study arms. Four studies reported complications or side effects, including sweating, itching, skin dryness, and constriction and tightness. None of the trials reported severe side effects. Two studies reported compliance showing no difference in compliance rates between stockings groups, although one study reported high initial levels of dropout due to discomfort, appearance, non-effectiveness and irritation. Four studies reported comfort, tolerance and acceptability. Two studies reported similar levels of tolerance and discomfort between groups. Discomfort was the main reason for indicating a preference for one type of stocking over another. None of the studies assessed quality of life. No conclusions regarding the optimum length or pressure of compression stockings could be made as there were no conclusive results from the included studies. AUTHORS' CONCLUSIONS: There is insufficient high-certainty evidence to determine whether or not compression stockings are effective as the sole and initial treatment of varicose veins in people without healed or active venous ulceration, or whether any type of stocking is superior to any other type. Future research should consist of large RCTs of participants with trunk varices either wearing or not wearing compression stockings to assess the efficacy of this intervention. If compression stockings are found to be beneficial, further studies assessing which length and pressure is the most efficacious could then take place.

Effect of testing for cancer on cancer- or venous thromboembolism (VTE)-related mortality and morbidity in people with unprovoked VTE.

BACKGROUND: Venous thromboembolism (VTE) is a collective term for two conditions: deep vein thrombosis (DVT) and pulmonary embolism (PE). A proportion of people with VTE have no underlying or immediately predisposing risk factors and the VTE is referred to as unprovoked. Unprovoked VTE can often be the first clinical manifestation of an underlying malignancy. This has raised the question of whether people with an unprovoked VTE should be investigated for an underlying cancer. Treatment for VTE is different in cancer and non-cancer patients and a correct diagnosis would ensure that people received the optimal treatment for VTE to prevent recurrence and further morbidity. Furthermore, an appropriate cancer diagnosis at an earlier stage could avoid the risk of cancer progression and lead to improvements in cancer-related mortality and morbidity. This is the third update of the review first published in 2015. OBJECTIVES: To determine whether testing for undiagnosed cancer in people with a first episode of unprovoked VTE (DVT of the lower limb or PE) is effective in reducing cancer- or VTE-related mortality and morbidity and to determine which tests for cancer are best at identifying treatable cancers early. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 5 May 2021. We also undertook reference checking to identify additional studies. SELECTION CRITERIA: Randomised and quasi-randomised trials in which people with an unprovoked VTE were allocated to receive specific tests for identifying cancer or clinically indicated tests only were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. We assessed the certainty of the evidence using GRADE criteria. We resolved any disagreements by discussion. The main outcomes of interest were all-cause mortality, cancer-related mortality and VTE-related mortality. MAIN RESULTS: No new studies were identified for this 2021 update. In total, four studies with 1644 participants are included. Two studies assessed the effect of extensive tests including computed tomography (CT) scanning versus tests at the physician's discretion, while the other two studies assessed the effect of standard testing plus positron emission tomography (PET)/CT scanning versus standard testing alone. For extensive tests including CT versus tests at the physician's discretion, the certainty of the evidence, as assessed according to GRADE, was low due to risk of bias (early termination of the studies). When comparing standard testing plus PET/CT scanning versus standard testing alone, the certainty of evidence was moderate due to a risk of detection bias. The certainty of the evidence was downgraded further as detection bias was present in one study with a low number of events. When comparing extensive tests including CT versus tests at the physician's discretion, pooled analysis on two studies showed that testing for cancer was consistent with either benefit or no benefit on cancer-related mortality (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.15 to 1.67; 396 participants; 2 studies; low-certainty evidence). One study (201 participants) showed that, overall, malignancies were less advanced at diagnosis in extensively tested participants than in participants in the control group. In total, 9/13 participants diagnosed with cancer in the extensively tested group had a T1 or T2 stage malignancy compared to 2/10 participants diagnosed with cancer in the control group (OR 5.00, 95% CI 1.05 to 23.76; low-certainty evidence). There was no clear difference in detection of advanced stages between extensive tests versus tests at the physician's discretion: one participant in the extensively tested group had stage T3 compared with four participants in the control group (OR 0.25, 95% CI 0.03 to 2.28; low-certainty evidence). In addition, extensively tested participants were diagnosed earlier than control group (mean: 1 month with extensive tests versus 11.6 months with tests at physician's discretion to cancer diagnosis from the time of diagnosis of VTE). Extensive testing did not increase the frequency of an underlying cancer diagnosis (OR 1.32, 95% CI 0.59 to 2.93; 396 participants; 2 studies; low-certainty evidence). Neither study measured all-cause mortality, VTE-related morbidity and mortality, complications of anticoagulation, adverse effects of cancer tests, participant satisfaction or quality of life. When comparing standard testing plus PET/CT screening versus standard testing alone, standard testing plus PET/CT screening was consistent with either benefit or no benefit on all-cause mortality (OR 1.22, 95% CI 0.49 to 3.04; 1248 participants; 2 studies; moderate-certainty evidence), cancer-related mortality (OR 0.55, 95% CI 0.20 to 1.52; 1248 participants; 2 studies; moderate-certainty evidence) or VTE-related morbidity (OR 1.02, 95% CI 0.48 to 2.17; 854 participants; 1 study; moderate-certainty evidence). Regarding stage of cancer, there was no clear difference for detection of early (OR 1.78, 95% 0.51 to 6.17; 394 participants; 1 study; low-certainty evidence) or advanced (OR 1.00, 95% CI 0.14 to 7.17; 394 participants; 1 study; low-certainty evidence) stages of cancer. There was also no clear difference in the frequency of an underlying cancer diagnosis (OR 1.71, 95% CI 0.91 to 3.20; 1248 participants; 2 studies; moderate-certainty evidence). Time to cancer diagnosis was 4.2 months in the standard testing group and 4.0 months in the standard testing plus PET/CT group (P = 0.88). Neither study measured VTE-related mortality, complications of anticoagulation, adverse effects of cancer tests, participant satisfaction or quality of life. AUTHORS' CONCLUSIONS: Specific testing for cancer in people with unprovoked VTE may lead to earlier diagnosis of cancer at an earlier stage of the disease. However, there is currently insufficient evidence to draw definitive conclusions concerning the effectiveness of testing for undiagnosed cancer in people with a first episode of unprovoked VTE (DVT or PE) in reducing cancer- or VTE-related morbidity and mortality. The results could be consistent with either benefit or no benefit. Further good-quality large-scale randomised controlled trials are required before firm conclusions can be made.

Pre-deployment programmes for building resilience in military and frontline emergency service personnel.

BACKGROUND: Military personnel and frontline emergency workers may be exposed to events that have the potential to precipitate negative mental health outcomes such as depression, symptoms of post-traumatic stress and even post-traumatic stress disorder (PTSD). Programmes have been designed to build psychological resilience before staff are deployed into the field. This review presents a synthesis of the literature on these "pre-deployment resilience-building programmes". OBJECTIVES: The objective of this review was to assess the effectiveness of programmes that seek to build resilience to potentially traumatic events among military and frontline emergency service personnel prior to their deployment. These resilience programmes were compared to other interventions, treatment as usual or no intervention. SEARCH METHODS: Studies were identified through searches of electronic databases including Ovid MEDLINE, Embase, PsycINFO, Web of Science and Google Scholar. The initial search took place in January 2019, with an updated search completed at the end of September 2020. SELECTION CRITERIA: Only studies that used a randomised controlled trial (RCT)/cluster-RCT methodology were included. The programmes being evaluated must have sought to build resilience prior to exposure to trauma. Study participants must have been 18 years or older and be military personnel or frontline emergency workers. DATA COLLECTION AND ANALYSIS: Studies that met the inclusion criteria were assembled. Data extracted included methods, participants' details, intervention details, comparator details, and information on outcomes. The primary outcomes of interest were resilience, symptoms of post-traumatic stress and PTSD. Secondary outcomes of interest included acute stress disorder, depression, social support, coping skills, emotional flexibility, self-efficacy, social functioning, subjective levels of aggression, quality of sleep, quality of life and stress. Assessment of risk of bias was also completed. A total of 28 studies were included in a narrative synthesis of results. MAIN RESULTS: All 28 included studies compared an experimental resilience building intervention versus a control or no intervention. There was a wide range of therapeutic modalities used, including cognitive behavioural therapy (CBT) informed programmes, biofeedback based programmes, stress-management programmes, mindfulness and relaxation programmes, neuropsychological-based programmes, and psychoeducational-informed programmes. The main outcomes are specified here, secondary outcomes such as depression, social support, coping skills, self-efficacy, subjective levels of aggression and stress are reported in text. No studies reported on the following pre-specified outcomes; acute stress disorder, emotional flexibility, social functioning, quality of sleep and quality of life. Resilience Eight studies reported resilience as an outcome. We narratively synthesised the data from these studies and our findings show that five of these interventions had success in building resilience in their respective samples. Two of the studies that reported significant results utilised a CBT approach to build resilience, while the other three successful programmes were mindfulness-based interventions. Symptoms of post-traumatic stress Our narrative synthesis of results included eight studies. Two of the eight studies produced significant reductions in symptoms of post traumatic stress compared to controls. These interventions used neuropsychological and biofeedback intervention models respectively. PTSD caseness Four studies reported PTSD caseness as an outcome. Our narrative synthesis of results suggests that evidence is mixed as to the effectiveness of these interventions in reducing clinical diagnosis of PTSD. One study of a neuropsychology-orientated Attention Bias Modification Training (AMBT) programme had success in reducing both symptoms of post-traumatic stress and numbers of participants receiving a diagnosis of PTSD. A stress-management programme reported that, when baseline differences in rates of pre-deployment mental health issues were controlled for, participants in the control condition were at 6.9 times the risk of a diagnosis of PTSD when compared to the intervention group. Given the diversity of intervention designs and theoretical orientations used (which included stress-management, neuropsychological and psychoeducational programmes), a definitive statement on the efficacy of pre-deployment programmes at reducing symptoms of post-traumatic stress and PTSD cannot be confidently offered. AUTHORS' CONCLUSIONS: While a number of evaluations of relevant programmes have been published, the quality of these evaluations limits our ability to determine if resilience-building programmes 'work' in terms of preventing negative outcomes such as depression, symptoms of post-traumatic stress and diagnoses of PTSD. Based on our findings we recommend that future research should: a) report pre-/post-means and standard deviation scores for scales used within respective studies, b) take the form of large, RCTs with protocols published in advance, and c) seek to measure defined psychological facets such as resilience, PTSD and stress, and measure these concepts using established psychometric tools. This will provide more certainty in future assessments of the evidence base. From a clinical implications point of view, overall there is mixed evidence that the interventions included in this review are effective at safe guarding military personnel or frontline emergency workers from experiencing negative mental health outcomes, including PTSD, following exposure to potentially traumatic events. Based on this, practitioners seeking to build resilience in their personnel need to be aware of the limitations of the evidence base. Practitioners should have modest expectations in relation to the efficacy of resilience-building programmes as a prophylactic approach to employment-related critical incident traumas.

Internet-based cognitive and behavioural therapies for post-traumatic stress disorder (PTSD) in adults.

BACKGROUND: Therapist-delivered trauma-focused psychological therapies are effective for post-traumatic stress disorder (PTSD) and have become the accepted first-line treatments. Despite the established evidence-base for these therapies, they are not always widely available or accessible. Many barriers limit treatment uptake, such as the number of qualified therapists available to deliver the interventions; cost; and compliance issues, such as time off work, childcare, and transportation, associated with the need to attend weekly appointments. Delivering Internet-based cognitive and behavioural therapy (I-C/BT) is an effective and acceptable alternative to therapist-delivered treatments for anxiety and depression. OBJECTIVES: To assess the effects of I-C/BT for PTSD in adults. SEARCH METHODS: We searched MEDLINE, Embase, PsycINFO and the Cochrane Central Register of Controlled Trials to June 2020. We also searched online clinical trial registries and reference lists of included studies and contacted the authors of included studies and other researchers in the field to identify additional and ongoing studies. SELECTION CRITERIA: We searched for RCTs of I-C/BT compared to face-to-face or Internet-based psychological treatment, psychoeducation, wait list, or care as usual. We included studies of adults (aged over 16 years), in which at least 70% of the participants met the diagnostic criteria for PTSD, according to the Diagnostic and Statistical Manual (DSM) or the International Classification of Diseases (ICD). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed abstracts, extracted data, and entered data into Review Manager 5. The primary outcomes were severity of PTSD symptoms and dropouts. Secondary outcomes included diagnosis of PTSD after treatment, severity of depressive and anxiety symptoms, cost-effectiveness, adverse events, treatment acceptability, and quality of life. We analysed categorical outcomes as risk ratios (RRs), and continuous outcomes as mean differences (MD) or standardised mean differences (SMDs), with 95% confidence intervals (CI). We pooled data using a fixed-effect meta-analysis, except where heterogeneity was present, in which case we used a random-effects model. We independently assessed the included studies for risk of bias and we evaluated the certainty of available evidence using the GRADE approach; we discussed any conflicts with at least one other review author, with the aim of reaching a unanimous decision. MAIN RESULTS: We included 13 studies with 808 participants. Ten studies compared I-C/BT delivered with therapist guidance to a wait list control. Two studies compared guided I-C/BT with I-non-C/BT. One study compared guided I-C/BT with face-to-face non-C/BT. There was substantial heterogeneity among the included studies. I-C/BT compared with face-to-face non-CBT Very low-certainty evidence based on one small study suggested face-to-face non-CBT may be more effective than I-C/BT at reducing PTSD symptoms post-treatment (MD 10.90, 95% CI 6.57 to 15.23; studies = 1, participants = 40). There may be no evidence of a difference in dropout rates between treatments (RR 2.49, 95% CI 0.91 to 6.77; studies = 1, participants = 40; very low-certainty evidence). The study did not measure diagnosis of PTSD, severity of depressive or anxiety symptoms, cost-effectiveness, or adverse events. I-C/BT compared with wait list Very low-certainty evidence showed that, compared with wait list, I-C/BT may be associated with a clinically important reduction in PTSD post-treatment (SMD -0.61, 95% CI -0.93 to -0.29; studies = 10, participants = 608). There may be no evidence of a difference in dropout rates between the I-C/BT and wait list groups (RR 1.25, 95% CI 0.97 to 1.60; studies = 9, participants = 634; low-certainty evidence). I-C/BT may be no more effective than wait list at reducing the risk of a diagnosis of PTSD after treatment (RR 0.53, 95% CI 0.28 to 1.00; studies = 1, participants = 62; very low-certainty evidence). I-C/BT may be associated with a clinically important reduction in symptoms of depression post-treatment (SMD -0.51, 95% CI -0.97 to -0.06; studies = 7, participants = 473; very low-certainty evidence). Very low-certainty evidence also suggested that I-C/BT may be associated with a clinically important reduction in symptoms of anxiety post-treatment (SMD -0.61, 95% CI -0.89 to -0.33; studies = 5, participants = 345). There were no data regarding cost-effectiveness. Data regarding adverse events were uncertain, as only one study reported an absence of adverse events. I-C/BT compared with I-non-C/BT There may be no evidence of a difference in PTSD symptoms post-treatment between the I-C/BT and I-non-C/BT groups (SMD -0.08, 95% CI -0.52 to 0.35; studies = 2, participants = 82; very low-certainty evidence). There may be no evidence of a difference between dropout rates from the I-C/BT and I-non-C/BT groups (RR 2.14, 95% CI 0.97 to 4.73; studies = 2, participants = 132; I² = 0%; very low-certainty evidence). Two studies found no evidence of a difference in post-treatment depressive symptoms between the I-C/BT and I-non-C/BT groups (SMD -0.12, 95% CI -0.78 to 0.54; studies = 2, participants = 84; very low-certainty evidence). Two studies found no evidence of a difference in post-treatment symptoms of anxiety between the I-C/BT and I-non-C/BT groups (SMD 0.08, 95% CI -0.78 to 0.95; studies = 2, participants = 74; very low-certainty evidence). There were no data regarding cost-effectiveness. Data regarding adverse effects were uncertain, as it was not discernible whether adverse effects reported were attributable to the intervention. AUTHORS' CONCLUSIONS: While the review found some beneficial effects of I-C/BT for PTSD, the certainty of the evidence was very low due to the small number of included trials. This review update found many planned and ongoing studies, which is encouraging since further work is required to establish non-inferiority to current first-line interventions, explore mechanisms of change, establish optimal levels of guidance, explore cost-effectiveness, measure adverse events, and determine predictors of efficacy and dropout.

Pharmacological treatment for psychotic depression.

BACKGROUND: Evidence is limited regarding the most effective pharmacological treatment for psychotic depression: monotherapy with an antidepressant, monotherapy with an antipsychotic, another treatment (e.g. mifepristone), or combination of an antidepressant plus an antipsychotic. This is an update of a review first published in 2005 and last updated in 2015. OBJECTIVES: 1. To compare the clinical efficacy of pharmacological treatments for patients with an acute psychotic depression: antidepressant monotherapy, antipsychotic monotherapy, mifepristone monotherapy, and the combination of an antidepressant plus an antipsychotic versus placebo and/or each other. 2. To assess whether differences in response to treatment in the current episode are related to non-response to prior treatment. SEARCH METHODS: A search of the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR); Ovid MEDLINE (1950-); Embase (1974-); and PsycINFO (1960-) was conducted on 21 February 2020. Reference lists of all included studies and related reviews were screened and key study authors contacted. SELECTION CRITERIA: All randomised controlled trials (RCTs) that included participants with acute major depression with psychotic features, as well as RCTs consisting of participants with acute major depression with or without psychotic features, that reported separately on the subgroup of participants with psychotic features. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias in the included studies, according to criteria from the Cochrane Handbook for Systematic Reviews of Interventions. Data were entered into RevMan 5.1. We used intention-to-treat data. Primary outcomes were clinical response for efficacy and overall dropout rate for harm/tolerance. Secondary outcome were remission of depression, change from baseline severity score, quality of life, and dropout rate due to adverse effects. For dichotomous efficacy outcomes (i.e. response and overall dropout), risk ratios (RRs) with 95% confidence intervals (CIs) were calculated.  Regarding the primary outcome of harm, only overall dropout rates were available for all studies. If the study did not report any of the response criteria as defined above, remission as defined here could be used as an alternative. For continuously distributed outcomes, it was not possible to extract data from the RCTs.  MAIN RESULTS: The search identified 3947 abstracts, but only 12 RCTs with a total of 929 participants could be included in the review. Because of clinical heterogeneity, few meta-analyses were possible. The main outcome was reduction in severity (response) of depression, not of psychosis. For depression response, we found no evidence of a difference between antidepressant and placebo (RR 8.40, 95% CI 0.50 to 142.27; participants = 27, studies = 1; very low-certainty evidence) or between antipsychotic and placebo (RR 1.13, 95% CI 0.74 to 1.73; participants = 201, studies = 2; very low-certainty evidence). Furthermore, we found no evidence of a difference in overall dropouts with antidepressant (RR 1.24, 95% CI 0.34 to 4.51; participants = 27, studies = 1; very low-certainty evidence) or antipsychotic monotherapy (RR 0.79, 95% CI 0.57 to 1.08; participants = 201, studies = 2; very low-certainty evidence). No evidence suggests a difference in depression response (RR 2.09, 95% CI 0.64 to 6.82; participants = 36, studies = 1; very low-certainty evidence) or overall dropouts (RR 1.79, 95% CI 0.18 to 18.02; participants = 36, studies = 1; very low-certainty evidence) between antidepressant and antipsychotic. For depression response, low- to very low-certainty evidence suggests that the combination of an antidepressant plus an antipsychotic may be more effective than antipsychotic monotherapy (RR 1.83, 95% CI 1.40 to 2.38; participants = 447, studies = 4), more effective than antidepressant monotherapy (RR 1.42, 95% CI 1.11 to 1.80; participants = 245, studies = 5), and more effective than placebo (RR 1.86, 95% CI 1.23 to 2.82; participants = 148, studies = 2). Very low-certainty evidence suggests no difference in overall dropouts between the combination of an antidepressant plus an antipsychotic versus antipsychotic monotherapy (RR 0.79, 95% CI 0.63 to 1.01; participants = 447, studies = 4), antidepressant monotherapy (RR 0.91, 95% CI 0.55 to 1.50; participants = 245, studies = 5), or placebo alone (RR 0.75, 95% CI 0.48 to 1.18; participants = 148, studies = 2). No study measured change in depression severity from baseline, quality of life, or dropouts due to adverse events. We found no RCTs with mifepristone that fulfilled our inclusion criteria. Risk of bias is considerable: we noted differences between studies with regards to diagnosis, uncertainties around randomisation and allocation concealment, treatment interventions (pharmacological differences between various antidepressants and antipsychotics), and outcome criteria. AUTHORS' CONCLUSIONS: Psychotic depression is heavily under-studied, limiting confidence in the conclusions drawn. Some evidence indicates that combination therapy with an antidepressant plus an antipsychotic is more effective than either treatment alone or placebo. Evidence is limited for treatment with an antidepressant alone or with an antipsychotic alone. Evidence for efficacy of mifepristone is lacking.