Sampling in epidemiological research: issues, hazards and pitfalls.

Surveys of people's opinions are fraught with difficulties. It is easier to obtain information from those who respond to text messages or to emails than to attempt to obtain a representative sample. Samples of the population that are selected non-randomly in this way are termed convenience samples as they are easy to recruit. This introduces a sampling bias. Such non-probability samples have merit in many situations, but an epidemiological enquiry is of little value unless a random sample is obtained. If a sufficient number of those selected actually complete a survey, the results are likely to be representative of the population. This editorial describes probability and non-probability sampling methods and illustrates the difficulties and suggested solutions in performing accurate epidemiological research.

Memantine for dementia in adults older than 40 years with Down's syndrome (MEADOWS): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Prevalence of Alzheimer's disease in people with Down's syndrome is very high, and many such individuals who are older than 40 years have pathological changes characteristic of Alzheimer's disease. Evidence to support treatment with Alzheimer's drugs is inadequate, although memantine is beneficial in transgenic mice. We aimed to assess safety and efficacy of memantine on cognition and function in individuals with Down's syndrome. METHODS: In our prospective randomised double-blind trial, we enrolled adults (>40 years) with karyotypic or clinically diagnosed Down's syndrome, with and without dementia, at four learning disability centres in the UK and Norway. We randomly allocated participants (1:1) to receive memantine or placebo for 52 weeks by use of a computer-generated sequence and a minimisation algorithm to ensure balanced allocation for five prognostic factors (sex, dementia, age group, total Down's syndrome attention, memory, and executive function scales [DAMES] score, and centre). The primary outcome was change in cognition and function, measured with DAMES scores and the adaptive behaviour scale (ABS) parts I and II. We analysed differences in DAMES and ABS scores between groups with analyses of covariance or quantile regression in all patients who completed the 52 week assessment and had available follow-up data. This study is registered, number ISRCTN47562898. FINDINGS: We randomly allocated 88 patients to receive memantine (72 [82%] had DAMES data and 75 [85%] had ABS data at 52 weeks) and 85 to receive placebo (74 [87%] and 73 [86%]). Both groups declined in cognition and function but rates did not differ between groups for any outcomes. After adjustment for baseline score, there were non-significant differences between groups of -4·1 (95% CI -13·1 to 4·8) in DAMES scores, -8·5 (-20·1 to 3·1) in ABS I scores, and 2·0 (-7·2 to 11·3) in ABS II scores, all in favour of controls. 10 (11%) of 88 participants in the memantine group and six (7%) of 85 controls had serious adverse events (p=0·33). Five participants in the memantine group and four controls died from serious adverse events (p=0·77). INTERPRETATION: There is a striking absence of evidence about pharmacological treatment of cognitive impairment and dementia in people older than 40 years with Down's syndrome. Despite promising indications, memantine is not an effective treatment. Therapies that are effective for Alzheimer's disease are not necessarily effective in this group of patients. FUNDING: Lundbeck.

Comparison of short and long versions of the Prudhoe Cognitive Function Test and the K-BIT in participants with intellectual impairment.

The Prudhoe Cognitive Function Test (PCFT) directly measures the cognitive abilities of people with intellectual impairment. This study examined the relationship between this instrument and the Kaufman Brief Intelligence Test (K-BIT) and two shorter versions of the same scale. High correlations between the verbal and performance sections of the K-BIT and the Long PCFT were found with correlation coefficients of 0.85 and 0.78, respectively. Extremely high correlations between the Short versions of the PCFT and the Long version were obtained at 0.97 for Form A and 0.98 for Form B, illustrating that both Short forms and the Long form are essentially interchangeable. The PCFT is a reliable and robust schedule in the assessment of cognitive function in this population.

An Intron 7 Polymorphism in APP Affects the Age of Onset of Dementia in Down Syndrome.

People with Down syndrome (DS) develop Alzheimer's disease (AD) with an early age of onset. A tetranucleotide repeat, attt(5-8), in intron 7 of the amyloid precursor protein has been associated with the age of onset of AD in DS in a preliminary study. The authors examine the impact of this polymorphism in a larger cohort of individuals with DS. Adults with DS were genotyped for attt(5-8) and APOE. The results were analysed with respect to the age of onset of dementia. The presence of three copies of the six-repeat allele resulted in onset of dementia seven years earlier than in the presence of other genotypes. Further study is essential to elucidate the mechanism by which this polymorphism functions, with an exciting opportunity to identify novel treatment targets relevant for people with DS and AD.

Is the content of confabulation positive? An experimental study.

There has been little experimental work investigating the emotional content of confabulation, despite clinical descriptions of self-serving and affectively positive biases. False memories were elicited in 10 amnesic confabulating patients, 10 healthy controls and four amnesic control patients without confabulation. Memory protocols of the interviews with these groups were presented to naïve raters who were asked to rate the emotional valence of the listed confabulations. The false memories of the confabulating patients were found to distort previous experiences in ways significantly more pleasant and self-enhancing than those of controls. It was also found paradoxically that the more depressed the patients' mood the more positive the content of their confabulations. These findings suggest that the content of confabulation is mostly positive. The results have implications for the role of emotion and motivation in confabulation, as well as for the clinical management of confabulating patients.

Self-serving confabulation in prose recall.

Recent studies suggest that the content of confabulation is mainly positive and self-enhancing. In this group study, we aimed to investigate whether this positive bias is specific to self-referent information. Confabulating amnesic patients, amnesic non-confabulating patients and healthy controls were asked to reproduce a series of short stories. We manipulated the emotional valence of the material by including positive, negative and neutral story plots. We also manipulated the self-reference of the material by including self-referent versus other-referent encoding instructions. Confabulating patients were as impaired as a group of amnesic patients in the amount of information they recalled, both groups being worse than healthy controls. Importantly, confabulating patients showed a selective bias in the negative self-referent condition, in that they recalled such information in a manner which portrayed a more positive image of themselves. This positive bias was not present in stories that were not encoded in a self-referent manner and it was not significantly correlated to patients' self-reported mood. We propose that both confabulation and its motivated content result from a deficit in the control and regulation of memory retrieval, which allows motivational factors to acquire a greater role than usual in determining which memories are selected for retrieval. To this extent, the self-enhancing content of confabulation could be explained as a neurogenic exaggeration of normal self-serving memory distortion.

A double blind randomised controlled clinical trial on the effect of transcutaneous spinal electroanalgesia (TSE) on low back pain.

A double blind randomised controlled clinical trial on the effect of transcutaneous spinal electroanalgesia (TSE) on low back pain was carried out in 58 patients attending a Pain Management Unit. Four TSE instruments, two active and two sham, were used and each patient was assigned randomly to one of these. Low back pain was rated by each patient using a visual analogue scale (VAS) immediately before and immediately after a single 20 min treatment of TSE and also daily for the week prior to, and the week following, the treatment. No significant difference in mean pain score was detected between the active and sham treated groups immediately after treatment or during the subsequent week. The Hospital, Anxiety and Depression scale (HAD) and the General Health Questionnaire (GHQ) were completed by each patient and there was a positive correlation between the scores achieved on these scales and the mean pain scores in both the active and sham treated groups. A post-trial problem was the discovery that the specification of the two active TSE machines differed from the manufacturer's specification. Thus, the output frequencies were either more (+10%) or less (-17%) while the maximum output voltages were both less (-40% and -20%), respectively. However, additional statistical analysis revealed no significant differences between the results obtained with the two active machines.

Self-enhancing confabulation: revisiting the motivational hypothesis.

We report a patient who developed spontaneous confabulation following surgical clipping of an anterior communicating artery aneurysm. An autobiographical memory test was used to measure the emotional valence of the patient's self-representations in true and false memories. We found that his confabulations included significantly more positive self-representations than his true memories and that the overall valence of his confabulations was more positive than that of his true memories and than that of the memories of five healthy control participants of the same age and educational attainment. It is proposed that while cognitive dysfunction may explain how confabulations are formed, emotional factors may explain which specific confabulations are constructed.

What does history teach us about factors associated with relapse in bipolar affective disorder? Presentation at Hilton hotel, Gateshead, 2 September 2005 at Symposium entitled managing The aftermath of mania.

When investigating treatments for any chronic condition it is essential to know the usual course of the illness concerned. The natural history of bipolar affective disorder has only been established relatively recently. This review examines the factors that affect the course of bipolar disorder from an historical perspective. These include the affective nature of the episodes and the influence of psychotic symptoms, age at onset of illness, length of episodes and cycles, gender, ethnicity, concurrent drug and alcohol use, occupational status and factors leading to chronicity. The pioneering work of Kraepelin and Angst established that episodes of illness in bipolar disorder increased in frequency over time and that earlier age of onset predicted more frequent episodes. More recent work has established that female subjects have a later onset of illness, that the frequency of episodes often decreases over time and that rapid cycling has a poorer response to treatment. Suggested criteria for inclusion of subjects into trials examining manic relapse are listed based on the findings from earlier work.

Pain following traumatic brain injury: Assessment and management.

Traumatic brain injury is frequently associated with painful complaints immediately after injury and subsequently. Early assessment of possible painful conditions can be made at the time of physical examination in those who are unable to give a history. Non-verbal signs of pain, including withdrawal of a painful limb or body part, irritability or tears should draw the attention of the assessing physician to a peripheral painful site. Treatment of conditions giving rise to pain can be made at this stage. Persistent pain may arise from a combination of physical and psychological factors and is best managed in a multidisciplinary pain clinic. Contributions from physicians in pain management, psychologists, physiotherapists and clinical nurse specialists enable a rehabilitation programme to take place. Treatments include analgesic drugs, graded exercise, cognitive-behavioural therapy, and transcutaneous electrical nerve stimulation. Rehabilitation of people who have ahead injury and pain takes longer than usual and separate pain management facilities should be developed for this population.

The detection of psychiatric illness and psychological handicaps in a British pain clinic population.

Ninety-seven successive patients attending the Newcastle Pain Relief Clinic completed a battery of psychiatric, psychological and pain questionnaires, and an extensive personal information form. All patients were seen by a physician who evaluated the extent of the pain arising from physical, psychiatric and psychological causes, and by a psychiatrist, who administered a structured interview schedule. Thirty-two percent of the patients had sufficient symptoms to be classified as psychiatric cases on the Present State Examination (PSE), a further 22% had minor neurotic symptoms and features of illness behaviour, 35% were categorized as organic, and 11% were unclassified. The Leeds General Depression Scale for Depression and Anxiety and the Beck Depression Inventory were the most effective of the psychiatric questionnaires used in separating the psychiatric patients from the remainder, and can be recommended as screening instruments for psychiatric illness in this population. Factors associated with a psychiatric diagnosis included female sex, larger number of present medications, greater reduction in activities compared to the period before the pain developed and increasing subjective pain from the onset of this.