No abstract

The neurobiology of tobacco use is poorly understood, possibly in part because the relevant mechanisms might differ depending on past nicotine exposure and degree of addiction. In the present study we investigated whether these factors might affect the role of dopamine (DA). Using the acute phenylalanine/tyrosine depletion method (APTD), DA synthesis was transiently decreased in three groups of abstinent smokers (n=47): (1) early low-frequency smokers, who had smoked a maximum of five cigarettes per day for less than one year, (2) stable low-frequency smokers smoking at the same level as early low-frequency smokers for at least 3 years, and (3) stable high-frequency smokers, who smoked a minimum of 10 or more cigarettes per day for at least 5 years. Motivation to obtain tobacco was measured using a progressive ratio breakpoint schedule for nicotine-containing and de-nicotinized cigarettes. Compared with a nutritionally balanced control mixture, APTD decreased the self-administration of nicotine-containing cigarettes, and this occurred in all three groups of smokers. The results suggest that DA influenced the willingness to sustain effort for nicotine reward, and this was seen in participants at all three levels of cigarette addiction. In the transition from sporadic to addicted use, the role of DA in the motivation to seek drug may change less than previously proposed.

ObjectiveThe Fluids in Shock (FiSh) Trial proposes to evaluate whether restrictive fluid bolus therapy (10 mL/kg) is more beneficial than current recommended practice (20 mL/kg) in the resuscitation of children with septic shock in the UK. This qualitative feasibility study aimed to explore acceptability of the FiSh Trial, including research without prior consent (RWPC), potential barriers to recruitment and participant information for a pilot trial.DesignQualitative interview study involving parents of children who had presented to a UK emergency department or been admitted to a paediatric intensive care unit with severe infection in the previous 3 years.ParticipantsTwenty-one parents (seven bereaved) were interviewed 16 (median) months since their child’s hospital admission (range: 1–41).ResultsAll parents said they would have provided consent for the use of their child’s data in the FiSh Trial. The majority were unfamiliar with RWPC, yet supported its use. Parents were initially concerned about the change from currently recommended treatment, yet were reassured by explanations of the current evidence base, fluid bolus therapy and monitoring procedures. Parents made recommendations about the timing of the research discussion and content of participant information. Bereaved parents stated that recruiters should not discuss research immediately after a child’s death, but supported a personalised postal ‘opt-out’ approach to consent.ConclusionsFindings show that parents whose child has experienced severe infection supported the proposed FiSh Trial, including the use of RWPC. Parents’ views informed the development of the pilot trial protocol and site staff training.Trial registration number ISRCTN15244462—results.

ObjectiveTo determine the feasibility of Fluids in Shock, a randomised controlled trial (RCT) of restricted fluid bolus volume (10 mL/kg) versus recommended practice (20 mL/kg).DesignNine-month pilot RCT with embedded mixed-method perspectives study.Setting13 hospitals in England.PatientsChildren presenting to emergency departments with suspected infection and shock after 20 mL/kg fluid.InterventionsPatients were randomly allocated (1:1) to further 10 or 20 mL/kg fluid boluses every 15 min for up to 4 hours if still in shock.Main outcome measuresThese were based on progression criteria, including recruitment and retention, protocol adherence, separation, potential trial outcome measures, and parent and staff perspectives.ResultsSeventy-five participants were randomised; two were withdrawn. 23 (59%) of 39 in the 10 mL/kg arm and 25 (74%) of 34 in the 20 mL/kg arm required a single trial bolus before the shock resolved. 79% of boluses were delivered per protocol in the 10 mL/kg arm and 55% in the 20 mL/kg arm. The volume of study bolus fluid after 4 hours was 44% lower in the 10 mL/kg group (mean 14.5 vs 27.5 mL/kg). The Paediatric Index of Mortality-2 score was 2.1 (IQR 1.6–2.7) in the 10 mL/kg group and 2.0 (IQR 1.6–2.5) in the 20 mL/kg group. There were no deaths. Length of hospital stay, paediatric intensive care unit (PICU) admissions and PICU-free days at 30 days did not differ significantly between the groups. In the perspectives study, the trial was generally supported, although some problems with protocol adherence were described.ConclusionsParticipants were not as unwell as expected. A larger trial is not feasible in its current design in the UK.Trial registration numberISRCTN15244462.

Both treatments have value as outpatient interventions for patients with AN. © 2016 Crown copyright. International Journal of Eating Disorders. (Int J Eat Disord 2016; 49:793-800).