Exploratory review of placebo characteristics reported in randomised placebo controlled antidepressant drug trials.

INTRODUCTION: Systematic reviews of randomised placebo controlled trials of antidepressants have found small and decreasing differences in outcome between pharmacological and placebo arms. Increased knowledge of placebo characteristics may provide greater understanding of antidepressant pharmacological effect. We conducted a systematic review to identify the presence of key placebo characteristics in a sample of antidepressant clinical trials. METHODS: 82 randomised placebo controlled trials of antidepressants, selected in 2 previous systematic reviews (Walsh et al. 2002; NICE 2009), were examined. Presence of placebo characteristics documented using detailed standardised form, with 5 domains: health care environment, practitioner characteristics, patient characteristics, practitioner-patient interaction, and non-pharmaceutical drug characteristics. First authors contacted where possible, and further clarification sought on placebo characteristics within trials. RESULTS: Percentage of trials reporting placebo characteristics within the 5 domains: health care setting 100%, environment 5%; practitioner profession 18%, status 0%, incentives 0%, gender 10%, age 4%, beliefs 6%; patient age 85%, gender 91%, ethnicity 41%, diagnosis and severity 100%, recruitment 16%, incentives 12%, co-morbidity 12%, expectation 0%, beliefs 0%; patient-practitioner interaction type of care 10%, number of visits 94%, empathy and congruence 2%; drug form 45% and frequency 57%. DISCUSSION: Placebo characteristics represent confounding variables which, if not adequately controlled for, could distort findings and conclusions about efficacy. The lack of systematic recording of many placebo characteristics in antidepressant drug trials is a cause for concern. To reduce imprecision and increase generalisability, future antidepressant clinical trials should consider the impact of key placebo characteristics and record their presence when disseminating findings.

Accidental discharge of brodifacoum baits into a freshwater lake: a case study.

Approximately 700 kg of cereal bait containing 20 ppm of the anticoagulant rodenticide brodifacoum was spilled into a southern New Zealand lake in 2010 from a helicopter being used to transport containers of brodifacoum bait for an aerial baiting operation. In the month after the spill no residual brodifacoum was detected in samples of lake water, sediment, benthic invertebrates, eels, and two birds.

A screening instrument for language in older people (Barnes Language Assessment).

This paper describes the development of a clinically viable tool for the assessment of language and associated cognitive skills in the older population which was instigated by the SIG Psychiatry of Old Age (South of England). A series of sub-tests is described. Data from normal older people is used to establish preliminary means and lower normal limits as a guide to distinguishing performance associated with normal age-related change from performance associated with pathology. The importance of allowing for the effects of normal age-related changes on language processing is illustrated. Data from older people with pathology attending clinics and hospital departments is also presented. Quantitative and qualitative language profiling is outlined. Data analysis suggests that the Barnes Language Assessment is able to profile language skills and difficulties. Indications for further research are discussed.

Learning multiplication facts: a study of children taught by discovery methods in England.

The development of multiplication skills was examined in a group of children ages 8 to 12 years who were taught by discovery methods. Strategies used by the children included direct retrieval, retrieval + calculation, and counting-in-series. Repeated addition was not observed. Retrieval was the fastest and least error-prone strategy; counting-in-series was the slowest and most error prone. Children ages 8 and 9 years used mainly mixed strategies. Children ages 10 to 12 years used mainly retrieval or retrieval and calculation for low operands, but reverted to back-up strategies for high operands based on the strategies available for low operands. There was a general shift away from less effective strategies across ages 8 to 12 years but, by the end of the primary school (age 11 years), relatively few children used the most effective strategy of retrieval for all operands. The development of effective strategies was related to nonverbal reasoning ability and to working memory capacity. The results are considered with reference to experiential and pedagogical models of multiplication.

Evidence for scripts in semantic dementia: Implications for theories of semantic memory.

This paper presents evidence that the breakdown of semantic memory in semantic dementia reveals the influence of two properties of script theory (Schank, 1982; Schank & Abelson, 1977). First, the physical and personal context of specific scripts supports meaning for words, objects, and locations that are involved in the script. Second, meaning is updated or transformed by a dynamic memory system that learns continuously from personal experience. In severe cases, semantic dementia exposes the basic level of this learning system from which all knowledge normally develops. It will be argued that the evidence supports a theory of semantic memory that represents meaning in a continuum of levels of meaning from the most specific and context-bound to the most generalisable and context-free. This contrasts with current theories of semantic memory that represent meaning as a collection of abstracted properties entirely removed from the context of events and activities.

Development of a screening instrument for language in older people (Barnes Language Assessment).

Language changes are associated with several types of age-related degenerative processes and are known to be particularly stressful for carers. Managing language and communication difficulties in older people has been shown to be an important aspect of dementia care. A test such as the one described here, might be a useful tool for health professionals planning care for older people with possible diagnoses of dementia. The information gained could be used as part of multi-disciplinary team assessment. This paper describes the development of a clinically viable assessment tool for the assessment of language and associated cognitive skills in the older population. Data on 43 normal older people were used to establish preliminary means and lower normal limits, as a guide to distinguishing performance associated with normal age-related change from performance associated with pathology. In the next phase data was collected from 43 older people with possible dementia who were attending clinics and hospital departments. The results suggest that the Barnes Language Assessment can profile language skills and difficulties and may be a useful diagnostic tool to contribute to language assessment of older people. Indications for further research are discussed.

Semantic representation and ease of predication.

Jones' (1985) Ease of Predication hypothesis, which states that underlying differences in the semantic representation of concrete and abstract words can be explained in terms of disproportionate numbers of semantic predicates, is explored in two experiments. The results suggest that (1) the advantage shown by concrete words in terms of greater number of predicates is only apparent for words of low frequency, and (2) Jones' case of predication variable does not accurately reflect predicate distributions, or differences in imageability. Rather, it appears to represent differences in concreteness. As such, the validity of this concept as the basis of theories of semantic representation is questioned. Models based on the assumption of a "richer" semantic representation for concrete words are therefore not supported.

Response biases in oral reading: an account of the co-occurrence of surface dyslexia and semantic dementia.

This paper reports a case study of a subject (EP) with a progressive impairment of semantic memory and a coincident surface dyslexia. These two disorders frequently occur together, but their association is not readily explained within current models of reading. This study investigated two theories that offer different principled accounts of this association, the "semantic glue hypothesis" (Patterson & Hodges, 1992) and the "summation hypothesis" (Hillis & Caramazza, 1991) and found both hypotheses wanting. Instead it was shown that when vestiges of word meaning remained, a lexical response was preferred, but when meaning was lost entirely, the evidence derived from sublexical processing appeared to bias selection of the response towards the regularized form.

Objects and properties: a study of the breakdown of semantic memory.

This paper reports a study of the breakdown of semantic memory in the case of a subject with semantic dementia. The first experiment shows that the subject failed to comprehend words of low familiarity and word frequency, even though the spoken word forms were recognised as familiar. Experiments 2 and 3 showed (a) that the recall of word meanings in definition tasks did not vary with the generality of the word meaning (e.g. category, basic level, or subordinate property) but varied instead with the concept familiarity and frequency of the name; (b) that the ability to verify properties of basic-level objects was not affected by the ability to comprehend the property name, but depended instead on the degree of knowledge demonstrated for the object name in definition tasks; (c) that properties were frequently verified correctly when the object had been defined only to the superordinate level. It is argued that the results do not support the widely held view that, in general, specific information is lost first when semantic memory breaks down. The selective failure to recall specific information for some word meanings is discussed with reference to two theoretical accounts.

Semantic dementia. Progressive fluent aphasia with temporal lobe atrophy.

We report five patients with a stereotyped clinical syndrome characterized by fluent dysphasia with severe anomia, reduced vocabulary and prominent impairment of single-word comprehension, progressing to a stage of virtually complete dissolution of the semantic components of language. A marked reduction in the ability to generate exemplars from restricted semantic categories (e.g. animals, vehicles, etc.) was a consistent and early feature. Tests of semantic memory demonstrated a radically impoverished knowledge about a range of living and man-made items. In contrast, phonology and grammar of spoken language were largely preserved, as was comprehension of complex syntactic commands. Reading showed a pattern of surface dyslexia. Autobiographical and day-to-day (episodic) memory were relatively retained. Non-verbal memory, perceptual and visuospatial abilities were also strikingly preserved. In some cases, behavioural and personality changes may supervene; one patient developed features of the Kluver-Bucy Syndrome. Radiological investigations have shown marked focal temporal atrophy in all five patients, and functional imaging by single positron emission tomography and positron emission tomography (one case) have implicated the dominant temporal lobe in all five. In the older literature, such cases would have been subsumed under the rubric of Pick's disease. Others have been included in series with progressive aphasia. We propose the term semantic dementia, first coined by Snowden et al. (1989), to designate this clinical syndrome.

Progressive loss of semantic memory in a case of Alzheimer's disease.

The breakdown of semantic memory in a patient with Alzheimer's disease was monitored by using a word-picture matching task. Performance deteriorated from a time when target pictures were selected virtually without error to a time when targets and semantically related distractor pictures were selected equally often. From this point, selection deteriorated rapidly to random. Knowledge of category membership and semantic features declined together over the same period. No consistency in item selection could be discerned, and successful selection in early tests was not influenced by either the name frequency or the familiarity of the target. The findings are argued to support a theory of access to semantic memory which is non-hierarchical.

Progressive loss of access to spoken word forms in a case of Alzheimer's disease.

We report the results of a longitudinal study of a progressive anomia in a patient with dementia of the Alzheimer type (DAT). The anomia cannot be attributed to a deficit within the semantic system, but appears instead to arise from impaired access to the phonological lexicon at a post-semantic stage of the naming process: a deficit that hitherto has not been reported in DAT. Specific naming responses were affected consistently by the disorder, showing that disorders of access are not invariably associated with inconsistent responding. Before specific responses disappeared from spontaneous use, there appeared to be an intervening stage at which some responses could be elicited by an initial phoneme cue, suggesting a low level of spontaneous activity of insufficient strength to elicit a response unaided. The frequency of the name affected naming performance, but did not appear to interact with the severity of the naming disorder, suggesting that the parameters of the normal naming system were unaffected. It is claimed that important new insights into the characteristics of progressive anomia have been obtained by taking a longitudinal approach.

Lexical capture: a developmental disorder of reading and spelling.

We report a case of a 35-year-old teacher, Louise, with a history of learning difficulties and current evidence of developmental phonological dyslexia and dysgraphia. Her reading, spelling, and remembering of novel stimuli written in conventional alphabetic script was poor, but she performed significantly better when the same items were written in the International Phonetic Alphabet, a system that she learned when studying linguistics. Her impaired performance in tasks of phonemic segmentation and short-term memory, which are generally associated with impaired reading and spelling of unfamiliar material, could not account for her specific difficulty with alphabetic stimuli. Instead, her problems appear to result from a lexical strategy, which we have called "lexical capture".

Phonological processes in reading: new evidence from acquired dyslexia.

This paper investigates the reading performance of two patients with acquired dyslexia. The first patient read aloud all classes of word (85-95 per cent correct), including affixed words, but failed to read aloud non-words. In addition, semantic judgments about written words were shown to be significantly impaired, relative to the ability to read the words aloud. These dissociations support the view that two independent lexical routes are available for reading aloud familiar words, a semantic route and a lexical phonological route. While unable to read aloud non-words, this patient retained the ability to segment orthographic and phonological stimuli. The reading of non-lexical material, therefore, does not appear to be mediated by lexical analogy procedures. Instead, it is suggested that a non-lexical phonological route exists that is clearly independent of lexical phonological procedures. This patient could process isolated written suffixes orthographically, but could only access complete phonological word forms. Suffixed words (but not isolated suffixes) appear to be represented in the phonological word store. The second patient read aloud non-words, but could not give phonetic sounds appropriate to single letters. This dissociation suggests that the reading aloud of non-words is not reliant upon grapheme-phoneme rules.