Chris Speed

Many primary care patients with raised blood pressure or depression drink potentially hazardous levels of alcohol. Brief interventions (BI) to reduce alcohol consumption may improve comorbid conditions and reduce the risk of future alcohol problems. However, research has not established their effectiveness in this patient population. This study aimed to establish the feasibility of definitive trials of BI to reduce excessive drinking in primary care patients with hypertension or mild to moderate depression. Thirteen general practices in North East England were randomized to the intervention or control arm of one of two parallel pilot trials. Adult patients drinking excessively and diagnosed with hypertension or mild-to-moderate depression received the Alcohol Use Disorders Identification Test (AUDIT) by postal survey. Consenting respondents scoring more than 7 on AUDIT (score range 0 to 40) received brief alcohol consumption advice plus an information leaflet (intervention) or an information leaflet alone (control) with follow-up at six months. Measurements included the numbers of patients eligible, recruited, and retained, and the AUDIT score and systolic/diastolic blood pressure of each patient or the nine-item Patient Health Questionnaire (PHQ-9) score. Acceptability was assessed via practitioner feedback and patient willingness to be screened, recruited, and retained at follow-up. In the hypertension trial, 1709 of 33,813 adult patients (5.1%) were eligible and were surveyed. Among the eligible patients, 468 (27.4%) returned questionnaires; 166 (9.6% of those surveyed) screened positively on AUDIT and 83 (4.8% of those surveyed) were recruited (50.0% of positive screens). Sixty-seven cases (80.7% of recruited patients) completed follow-up at six months. In the depression trial, 1,044 of 73,146 adult patients (1.4%) were eligible and surveyed. Among these eligible patients, 215 (20.6%) responded; 104 (10.0% of those surveyed) screened positively on AUDIT and 29 (2.8% of those surveyed) were recruited (27.9% of positive screens). Nineteen cases (65.5% of recruited patients) completed follow-up at six months. Recruitment and retention rates were higher in the hypertension trial than in the depression trial. A full brief intervention trial appears feasible for primary care patients with hypertension who drink excessively. High AUDIT scores in the depression trial suggest the importance of alcohol intervention in this group. However, future work may require alternative screening and measurement procedures. Current Controlled Trials ISRCTN89156543 ; registered 21 October 2013.

Some patients with depression do not respond to first and second line conventional antidepressants and are therefore characterised as suffering from treatment refractory depression (TRD). On-going psychosocial stress and dysfunction of the hypothalamic-pituitary-adrenal axis are both associated with an attenuated clinical response to antidepressants. Preclinical data shows that co-administration of corticosteroids leads to a reduction in the ability of selective serotonin reuptake inhibitors to increase forebrain 5-hydroxytryptamine, while co-administration of antiglucocorticoids has the opposite effect. A Cochrane review suggests that antiglucocorticoid augmentation of antidepressants may be effective in treating TRD and includes a pilot study of the cortisol synthesis inhibitor, metyrapone. The Antiglucocorticoid augmentation of anti-Depressants in Depression (The ADD Study) is a multicentre randomised placebo controlled trial of metyrapone augmentation of serotonergic antidepressants in a large population of patients with TRD in the UK National Health Service. Patients with moderate to severe treatment refractory Major Depression aged 18 to 65 will be randomised to metyrapone 500 mg twice daily or placebo for three weeks, in addition to on-going conventional serotonergic antidepressants. The primary outcome will be improvement in Montgomery-Åsberg Depression Rating Scale score five weeks after randomisation (i.e. two weeks after trial medication discontinuation). Secondary outcomes will include the degree of persistence of treatment effect for up to 6 months, improvements in quality of life and also safety and tolerability of metyrapone. The ADD Study will also include a range of sub-studies investigating the potential mechanism of action of metyrapone. Strengths of the ADD study include broad inclusion criteria meaning that the sample will be representative of patients with TRD treated within the UK National Health Service, longer follow up, which to our knowledge is longer than any previous study of antiglucocorticoid treatments in depression, and the range of mechanistic investigations being carried out. The data set acquired will be a rich resource for a range of research questions relating to both refractory depression and the use of antiglucocorticoid treatments. Current Controlled Trials: ISRCTN45338259 ; EudraCT Number: 2009-015165-31.

Randomised controlled trials (RCTs) are generally regarded as the gold standard for evaluating health care interventions. The level of uncertainty around a trial's estimate of effect is, however, frequently linked to how successful the trial has been in recruiting and retaining participants. As recruitment is often slower or more difficult than expected, with many trials failing to reach their target sample size within the timescale and funding originally envisaged, the results are often less reliable than they could have been. The high number of trials that require an extension to the recruitment period in order to reach the required sample size potentially delays the introduction of more effective therapies into routine clinical practice. Moreover, it may result in less research being undertaken as resources are redirected to extending existing trials rather than funding additional studies.

Background: Uncertainties surrounding the effectiveness and cost-effectiveness of childhood tonsillectomy for recurrent sore throat led the NHS Health Technology Assessment Programme to commission this research to evaluate the effectiveness and cost-effectiveness of tonsillectomy and adeno-tonsillectomy in comparison with standard non-surgical management in children aged under 16 with recurrent throat infections. The aim is to evaluate if tonsillectomy and adeno-tonsillectomy reduces the number of episodes of sore throats among children to a clinically significant extent.Methods/design: A simple prospective pragmatic randomised controlled trial with economic analysis and prospective cohort study of non-trial participants comparing surgical intervention with conventional medical treatment. The treatment arm will receive tonsillectomy and adeno-tonsillectomy while in the control arm non-surgical conventional medical treatment only will be used. The primary outcome measure will be reported number of episodes of sore throat over two years with secondary outcomes measures of reported number of episodes of sore throat, otitis media and upper respiratory tract infection which invoke a GP consultation; reported number of symptom-free days; reported severity of sore throats and surgical and anaesthetic morbidity. The study will take place in five hospitals in the UK. The trial population will be 406 children aged 4–15 on their last birthday with recurrent sore throat referred by primary care to the 5 otolaryngology departments. The duration of the study is seven years (July 2001- July 2008).Discussion: As with all pragmatic randomised controlled trials it is impossible to control the external environment in which the research is taking place. Since this trial began a number of factors have arisen which could affect the outcome including; a reduction in the incidence of respiratory tract infections, marked socio-economic differences in consultation rates, the results from the National Prospective Tonsillectomy Audit and the Government's waiting list initiatives.