Reducing smoking in adolescents: cost-effectiveness results from the cluster randomized ASSIST (A Stop Smoking In Schools Trial)

Introduction: School-based smoking prevention programmes can be effective, but evidence on cost-effectiveness is lacking. We conducted a cost-effectiveness analysis of a school-based “peer-led” intervention.<p></p> Methods: We evaluated the ASSIST (A Stop Smoking In Schools Trial) programme in a cluster randomized controlled trial. The ASSIST programme trained students to act as peer supporters during informal interactions to encourage their peers not to smoke. Fifty-nine secondary schools in England and Wales were randomized to receive the ASSIST programme or usual smoking education. Ten thousand seven hundred and thirty students aged 12–13 years attended participating schools. Previous work has demonstrated that the ASSIST programme achieved a 2.1% (95% CI = 0%–4.2%) reduction in smoking prevalence. We evaluated the public sector cost, prevalence of weekly smoking, and cost per additional student not smoking at 24 months.<p></p> Results: The ASSIST programme cost of £32 (95% CI = £29.70–£33.80) per student. The incremental cost per student not smoking at 2 years was £1,500 (95% CI = £669–£9,947). Students in intervention schools were less likely to believe that they would be a smoker at age 16 years (odds ratio [OR] = 0.80; 95% CI = 0.66–0.96).<p></p> Conclusions: A peer-led intervention reduced smoking among adolescents at a modest cost. The intervention is cost-effective under realistic assumptions regarding the extent to which reductions in adolescent smoking lead to lower smoking prevalence and/or earlier smoking cessation in adulthood. The annual cost of extending the intervention to Year 8 students in all U.K. schools would be in the region of £38 million and could result in 20,400 fewer adolescent smokers.<p></p&gt

Ealing brighter futures intensive engagement model: working with adolescents in and on the edge of care

Ealing’s Brighter Futures Intensive Engagement Model is a complex, whole system intervention that was launched in June 2015. Its implementation was intended to support and enable the children’s social care workforce to build effective, consistent relationships with adolescents, families, communities and carers, and to use those successful relationships to bring about positive change

HOPE: Help fOr People with money, employment, benefit or housing problems: study protocol for a randomised controlled trial

Background: Self-harm and suicide increase in times of economic recession. Factors including job loss, austerity measures, financial difficulties and house repossession contribute to the risk. Vulnerable individuals commonly experience difficulties in navigating the benefits system and in accessing the available sources of welfare and debt advice, and this contributes to their distress. Our aim is to determine the feasibility and acceptability of a brief psychosocial intervention (the “HOPE” service) for people presenting to hospital emergency departments (ED) following self-harm or in acute distress because of financial, employment, or welfare (benefit) difficulties. Method: A pilot study including randomisation will be employed to determine whether it is possible to undertake a full-scale trial. Twenty people presenting to the ED who have self-harmed, have suicidal thoughts and depression and/or are in crisis and where financial, employment or benefit problems are cited as contributory factors will be asked to consent to random allocation to the intervention or control arm on a 2:1 basis. People who require secondary mental health follow-up will be excluded. Those randomised to the intervention arm will receive up to six sessions with a mental health worker who will provide practical help with financial and other problems. The mental health worker will use the motivational interviewing method in their interactions with participants. Control participants will receive one session signposting them to existing relevant support organisations. Participants will be followed up after 3 months. Participants and the mental health workers will take part in qualitative interviews to enable refinement of the intervention. The acceptability of outcome measures including the PHQ-9, GAD-7, repeat self-harm, EQ5D-5L and questions about debt, employment and welfare benefits will be explored. Discussion: This study will assess whether a full-scale randomised trial of this novel intervention to prevent self-harm among those distressed because of financial difficulties is feasible, including the acceptability of randomisation, potential rate of recruitment and the acceptability of outcome measures. Trial registration: ISRCTN5853124

Cannabidiol interactions with voltage-gated sodium channels

Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, and electrophysiology to show the functional effects of binding CBD to these channels. CBD binds at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition. Modelling studies suggest why the closely-related psychoactive compound tetrahydrocannabinol may not have the same effects on these channels. Finally, comparisons are made with the TRPV2 channel, also recently proposed as a target site for CBD. In summary, this study provides novel insight into a possible mechanism for CBD interactions with sodium channels

KH domains with impaired nucleic acid binding as a tool for functional analysis

In eukaryotes, RNA-binding proteins that contain multiple K homology (KH) domains play a key role in coordinating the different steps of RNA synthesis, metabolism and localization. Understanding how the different KH modules participate in the recognition of the RNA targets is necessary to dissect the way these proteins operate. We have designed a KH mutant with impaired RNA-binding capability for general use in exploring the role of individual KH domains in the combinatorial functional recognition of RNA targets. A double mutation in the hallmark GxxG loop (GxxG-to-GDDG) impairs nucleic acid binding without compromising the stability of the domain. We analysed the impact of the GDDG mutations in individual KH domains on the functional properties of KSRP as a prototype of multiple KH domain-containing proteins. We show how the GDDG mutant can be used to directly link biophysical information on the sequence specificity of the different KH domains of KSRP and their role in mRNA recognition and decay. This work defines a general molecular biology tool for the investigation of the function of individual KH domains in nucleic acid binding proteins

Cannabidiol interactions with voltage-gated sodium channels

Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for the treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high-resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, and electrophysiology to show the functional effects of binding CBD to these channels. CBD binds at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition. Modelling studies suggest why the closely-related psychoactive compound tetrahydrocannabinol may not have the same effects on these channels. Finally, comparisons are made with the TRPV2 channel, also recently proposed as a target site for CBD. In summary, this study provides novel insight into a possible mechanism for CBD interactions with sodium channels

Results of an international survey on the investigation and endovascular management of cerebral vasospasm and delayed cerebral ischemia

Background: Delayed cerebral ischemia (DCI) is a major cause of morbidity and mortality in aneurysmal subarachnoid hemorrhage. Endovascular management of this condition offers a new hope in preventing adverse outcome; however, a uniform standard of practice is lacking owing to a paucity of clinical trials. We conducted an international survey on the use of investigative and endovascular techniques in the treatment of DCI to assess the variability of current practice. Methods: Neurovascular neurosurgeons and neuroradiologists were contacted through professional societies from America, United Kingdom, Europe, and Australasia. Members were invited to complete a 13-item questionnaire regarding screening techniques, first-line and second-line therapies in endovascular intervention, and the role of angioplasty. Answers were compared using χ2 testing for nonparametric data. Results: Data from 344 respondents from 32 countries were analyzed: 167 non-United States and 177 U.S. respondents. More than half of all clinicians had 10+ years of experience in units with a mixture of higher and lower case volumes. Daily transcranial Doppler ultrasonography was the most commonly used screening technique by both U.S. (70%) and non-U.S. (53%) practitioners. Verapamil was the most common first-line therapy in the United States, whereas nimodipine was most popular in non-U.S. countries. Angioplasty was performed by 83% of non-U.S. and 91% of U.S. clinicians in the treatment of vasospasm; however, more U.S. clinicians reported using angioplasty for distal vasospasm. Conclusions: Treatment practices for DCI vary considerably, with the greatest variability in the choice of agent for intra-arterial therapy. Our data demonstrate the wide variation of approaches in use at present. However, without further clinical trials and development of a uniform standard of best practice, variability in treatment and outcome for DCI is likely to continue

Randomized clinical trial of postoperative chewing gum versus standard care after colorectal resection

Background Chewing gum may stimulate gastrointestinal motility, with beneficial effects on postoperative ileus suggested in small studies. The primary aim of this trial was to determine whether chewing gum reduces length of hospital stay (LOS) after colorectal resection. Secondary aims included examining bowel habit symptoms, complications and healthcare costs. Methods This clinical trial allocated patients randomly to standard postoperative care with or without chewing gum (sugar-free gum for at least 10 min, four times per day on days 1–5) in five UK hospitals. The primary outcome was LOS. Cox regression was used to calculate hazard ratios for LOS. Results Data from 402 of 412 patients, of whom 199 (49·5 per cent) were allocated to chewing gum, were available for analysis. Some 40 per cent of patients in both groups had laparoscopic surgery, and all study sites used enhanced recovery programmes. Median (i.q.r.) LOS was 7 (5–11) days in both groups (P = 0·962); the hazard ratio for use of gum was 0·94 (95 per cent c.i. 0·77 to 1·15; P = 0·557). Participants allocated to gum had worse quality of life, measured using the EuroQoL 5D-3L, than controls at 6 and 12 weeks after operation (but not on day 4). They also had more complications graded III or above according to the Dindo–Demartines–Clavien classification (16 versus 6 in the group that received standard care) and deaths (11 versus 0), but none was classed as related to gum. No other differences were observed. Conclusion Chewing gum did not alter the return of bowel function or LOS after colorectal resection