Assessing the potential of upper respiratory tract point-of-care testing: a systematic review of the prognostic significance of upper respiratory tract microbes.

OBJECTIVES: Microbial point-of-care testing (POCT) has potential to revolutionize clinical care. Understanding the prognostic value of microbes identified from the upper respiratory tract (a convenient sampling site) is a necessary first step to understand potential for upper respiratory tract POCTs in assisting antimicrobial treatment decisions for respiratory infections (RTIs). The aim was to investigate the relationship between upper respiratory tract microbial detection and disease prognosis, including effects of antimicrobial use. METHODS: Data sources were the MEDLINE and Embase databases. Study eligibility criteria consisted of quantitative studies reporting microbiological and prognostic data from patients of all age groups presenting with RTI. Patients presenting to healthcare or research settings with RTI participated. Interventions included upper respiratory tract swab. The methods used were systematic review and meta-analysis. RESULTS: Searches identified 5156 articles, of which 754 were duplicates and 4258 excluded on title or abstract. A total of 144 full texts were screened; 21 articles were retained. Studies reported data for 15 microbes and 26 prognostic measures (390 potential associations). One hundred and seven (27%) associations were investigated statistically, of which 38 (36%) were significant. Most studies reported only prognostic value of test positive results. Meta-analyses suggested hospitalization duration was longer for patients with respiratory syncytial virus than adenovirus and influenza, but significant heterogeneity was observed between studies. CONCLUSIONS: A quarter of potential prognostic associations have been investigated. Of these, a third were significant, suggesting considerable potential for POCT. Future research should investigate prognostic value of positive and negative tests, and interactions between test results, use of antimicrobials and microbial resistance.

Cognitive changes in alcohol-induced psychotic disorder.

AIMS: This study aimed to explore the neuro-cognitive deficits of alcohol-induced psychotic disorder as compared to the cognitive deficits of uncomplicated alcohol dependence. METHODS: Participants were recruited from the acute psychiatric admission wards of the Department of Psychiatry, University of Stellenbosch and Stikland and Tygerberg Academic Hospitals in the Western-Cape, South Africa. Participants who met DSM IV TR criteria (American Psychiatric Association. Diagnostic and statistical manual of mental disorders. American Psychiatric Association, Washington, DC, 2000) for Alcohol Dependence and for alcohol-induced psychotic disorder, respectively, were included. Participants who met criteria for another current DSM IV TR Axis I disorder were excluded. A structured interview was done prior to neuropsychological assessment to ascertain current mental state and to obtain relevant demographic detail and history. Neuropsychological assessments were performed and supervised by clinical psychologists at either Tygerberg or Stikland Hospital. RESULTS: The groups were matched demographically with similar period of abstinence prior to assessment. The alcohol-induced psychotic disorder group experienced first psychotic symptoms at age 35. The results reflected statistically significant differences on tasks measuring immediate memory; recall upon delay; exaggeration of memory difficulty and abstract thinking. CONCLUSION: This study concurs with earlier literature that some cognitive deficits are greater in alcohol-induced psychotic disorder compared to uncomplicated alcohol dependence.

Proof of concept for a novel insecticide bioassay based on sugar feeding by adult Aedes aegypti (Stegomyia aegypti).

Aedes aegypti L. (Stegomyia aegypti) (Diptera: Culicidae) is the principal vector of dengue and yellow fever viruses in tropical and subtropical regions of the world. Disease management is largely based on mosquito control achieved by insecticides applied to interior resting surfaces and through space sprays. Population monitoring to detect insecticide resistance is a significant component of integrated disease management programmes. We developed a bioassay method for assessing insecticide susceptibility based on the feeding activity of mosquitoes on plant sugars. Our prototype sugar-insecticide feeding bioassay system was composed of inexpensive, disposable components, contained minimal volumes of insecticide, and was compact and highly transportable. Individual mosquitoes were assayed in a plastic cup that contained a sucrose-permethrin solution. Trypan blue dye was added to create a visual marker in the mosquito's abdomen for ingested sucrose-permethrin solution. Blue faecal spots provided further evidence of solution ingestion. With the sugar-insecticide feeding bioassay, the permethrin susceptibility of Ae. aegypti females from two field-collected strains was characterized by probit analysis of dosage-response data. The field strains were also tested by forced contact of females with permethrin residues on filter paper. Dosage-response patterns were similar, indicating that the sugar-insecticide feeding bioassay had appropriately characterized the permethrin susceptibility of the two strains.

Hypervigilance for fear after basolateral amygdala damage in humans.

Recent rodent research has shown that the basolateral amygdala (BLA) inhibits unconditioned, or innate, fear. It is, however, unknown whether the BLA acts in similar ways in humans. In a group of five subjects with a rare genetic syndrome, that is, Urbach-Wiethe disease (UWD), we used a combination of structural and functional neuroimaging, and established focal, bilateral BLA damage, while other amygdala sub-regions are functionally intact. We tested the translational hypothesis that these BLA-damaged UWD-subjects are hypervigilant to facial expressions of fear, which are prototypical innate threat cues in humans. Our data indeed repeatedly confirm fear hypervigilance in these UWD subjects. They show hypervigilant responses to unconsciously presented fearful faces in a modified Stroop task. They attend longer to the eyes of dynamically displayed fearful faces in an eye-tracked emotion recognition task, and in that task recognize facial fear significantly better than control subjects. These findings provide the first direct evidence in humans in support of an inhibitory function of the BLA on the brain's threat vigilance system, which has important implications for the understanding of the amygdala's role in the disorders of fear and anxiety.

Regulatory T cells expressing granzyme B play a critical role in controlling lung inflammation during acute viral infection.

The inflammatory response to lung infections must be tightly regulated, enabling pathogen elimination while maintaining crucial gas exchange. Using recently described "depletion of regulatory T cell" (DEREG) mice, we found that selective depletion of regulatory T cells (Tregs) during acute respiratory syncytial virus (RSV) infection enhanced viral clearance but increased weight loss, local cytokine and chemokine release, and T-cell activation and cellular influx into the lungs. Conversely, inflammation was decreased when Treg numbers and activity were boosted using interleukin-2 immune complexes. Unexpectedly, lung (but not draining lymph node) Tregs from RSV-infected mice expressed granzyme B (GzmB), and bone marrow chimeric mice with selective loss of GzmB in the Treg compartment displayed markedly enhanced cellular infiltration into the lung after infection. A crucial role for GzmB-expressing Tregs has not hitherto been described in the lung or during acute infections, but may explain the inability of children with perforin/GzmB defects to regulate immune responses to infection. The effects of RSV infection in mice with defective immune regulation closely parallel the observed effects of RSV in children with bronchiolitis, suggesting that the pathogenesis of bronchiolitis may involve an inability to regulate virus-induced inflammation.

Clinical trials--a brave new partnership: a new doctor-patient working relationship in research.

An outline of the development of a "brave new partnership" in clinical trials is provided in this specific personal account. This paper was one of several delivered in November 2007 by colleagues deemed to have contributed to the distinguished career of Professor Michael Baum, at a Festschrift convened to honour him. This account describes this strange, new doctor-patient relationship in the research process that we developed, both in our dialogues and in the work of the Consumers' Advisory Group for Clinical Trials (CAG-CT) that we jointly founded. This work formed but one facet of his outstanding contribution to society and academe, in the fields of medicine, ethics and science.

Interventions to improve risk communication in clinical genetics: systematic review.

OBJECTIVE: Effective risk communication may enable clients to participate effectively in decision-making about their health and health care. A systematic review of existing literature on risk communication in genetics, and its effects on key outcomes for clients, was undertaken. METHOD: Systematic searching of six electronic databases and data extraction from included studies; narrative synthesis of results. RESULTS: Twenty-eight studies were included, principally from cancer genetics. Sixteen communication interventions have been evaluated, generally showing improvements in cognitive outcomes for users, such as knowledge, understanding and risk perception, and without adverse effects on anxiety, cancer-related worry and depression. However, often it was the supportive or emotional elements of counselling that provided benefits to users, rather than the informational or educational elements. Similar results were found in 12 further studies of decision aids which also appear to achieve shorter consultations that can focus more on the supportive elements of counselling. CONCLUSION: For both communication models and decision aids, the supportive or emotional elements of counselling provided more benefits to users than the informational or educational elements. PRACTICE IMPLICATIONS: Debate is required on how to strike a balance between the medical model, its agenda and perceived requirements to disclose or discuss a range of issues and the sometimes competing goals of addressing users' concerns, needs for support, issues of loss and relationship problems.

Clinical and molecular characterization of lipoid proteinosis in Namaqualand, South Africa.

BACKGROUND: Lipoid proteinosis (LiP) is a rare autosomal recessive disorder characterized by a hoarse voice, warty skin infiltration and scarring. Mutations within the extracellular matrix protein 1 (ECM1) gene cause LiP. Since the early 1970s it has been recognized that South Africa has one of the largest groups of LiP patients worldwide, suggesting a probable founder effect. As LiP patients present with considerable clinical variability, this group of patients offers a unique opportunity for genotype-phenotype correlation. OBJECTIVES: To assess the clinical features and the molecular basis of LiP in patients from the Namaqualand area of the Northern Cape province of South Africa and to examine molecular evidence for a founder effect. SUBJECTS AND METHODS: The LiP patient cohort consisted of 29 Coloured patients from Namaqualand and a further seven Caucasoid patients from other areas of South Africa. The control group included 100 healthy geographically and ethnically matched individuals from Namaqualand. Samples were collected after informed consent and with ethics committee approval from the University of the Witwatersrand. LiP patients were examined clinically and a structured recording sheet was completed. A brief neurological evaluation was also performed. The LiP founder effect was investigated at the molecular level by ECM1 mutation detection and haplotype analysis. RESULTS: The most consistent clinical signs for a diagnosis of LiP in this group were a hoarse voice and thickened sublingual frenulum leading to restricted tongue movement. Homozygosity for a nonsense mutation in exon 7 of the ECM1 gene, Q276X, was identified in all patients (Coloured and Caucasoid). Despite this genetic homogeneity, considerable clinical variability in skin presentation and psychiatric involvement was observed. Haplotype analysis using markers from a 9.98-Mb region around the ECM1 locus confirmed the founder effect with a founder core haplotype, 19-Q276X-12 (ND1-ECM1-D1S2343), in all but four LiP-associated alleles (n = 58). A LiP carrier rate of 1 in 9 was observed among the 100 Namaqualand controls, predicting a LiP incidence of 1 in 324 in this community. CONCLUSIONS: Although several consistent clinical features in LiP patients homozygous for the Q276X mutation in the ECM1 gene were observed, there remains considerable clinical variability. This suggests the action of genetic and environmental modifiers of disease severity. Strong molecular evidence supports a single founder effect for the high prevalence of LiP in South Africans, both Coloured and Caucasoid.

A survey of breast cancer patients' views on entry into several clinical studies.

During the course of their treatment and follow-up, women with breast cancer are likely to be asked to join a number of different clinical studies. Some local research ethics committees have expressed concerns about entry of individual patients into multiple research studies. A survey was undertaken to improve understanding of patients' own perceptions of participation in several clinical studies. A total of 96 patients who had previously undergone surgery for breast cancer from January to June 2000 were sent a questionnaire 6-12 months after completion of primary treatment. Eighty four per cent of questionnaires were returned of which 62% were from patients who had been approached to enter at least one clinical study. Sixty-four per cent of patients believed that there should not be a limit on the number of clinical studies offered to patients. Furthermore, three quarters of all patients would have considered entering more than one study if adequate explanation and written information were provided. Most patients felt that their participation in a clinical study was worthwhile and no patients surveyed regretted their decision to take part in a study. Almost two-thirds of patients who returned questionnaires believed there should not be a maximum number of studies offered to them. This survey suggests that the majority of patients are prepared to participate in more than one clinical study when adequate information and explanation are provided.

Consumers' views of quality in the consultation and their relevance to 'shared decision-making' approaches.

BACKGROUND: There is a recognized need to assess the effects of shared decision-making and other communication interventions. However, the outcomes usually assessed for evidence of 'effectiveness' are determined by researchers and have not been based on consumers' views. AIM: This study aimed to identify the important outcomes of consultations for consumers, and to compare with those reported in the current literature. SETTING AND PARTICIPANTS: Forty-seven participants attending six focus group interviews. Most interviews took place in and all were orientated towards the UK primary care setting. METHODS: Focus group study. RESULTS: Many affective outcomes were identified, consistent with the current literature trends. However, many cognitive and behavioural outcomes that are assessed in the current literature were not noted by participants as important. Furthermore, a broader range of outcomes than is evident in the current literature was viewed as important to these participants. CONCLUSIONS: There is a need to revisit the outcomes which are assessed in decision-making and communication research. The outcomes of greatest importance to consumers must be identified and confirmed by new research which is based directly on the views of consumers themselves.

Pairing accountability with responsibility--the consequences of screening 'promotion'.

The chain of accountability, beginning with the inadequate information provision to women being invited for mammographic screening over the last decade, against a background of changing attitudes in women and increased understanding of DCIS, and the consequences and effectiveness of mammographic screening, is explored. In particular, an example is used of family repercussions arising from facile, unjustified extrapolation by insurance brokers of genetic risk by use of the 'breast cancer' label in a case of diagnosis of screen-detected ductal carcinoma in situ (DCIS) to seek to unjustly deny, restrict or withhold. The question posed is: where does the responsibility lie for such a serious, previously unadvised repercussion in a public health programme imposed on 'healthy' women, promoted to them in a coercive manner with unbalanced, inadequate information, and still not revised in the light of recent findings and GMC guidelines?

Accuracy of prediction of walking for young stroke patients by use of the FIM.

BACKGROUND AND PURPOSE: Clinical prediction of walking outcome after a stroke is essential for effective discharge planning. However, its accuracy has hardly been explored. This study took place in a regional unit admitting patients with complex neurological disabilities for specialist inpatient rehabilitation. The aim was to compare predicted outcome (goal score) with achieved outcome (discharge score) on the seven-point locomotion subscale of the Functional Independence Measure (FIM), to evaluate its precision and identify factors influencing accuracy. METHOD: Admission, goal and discharge scores were analysed retrospectively for 141 subjects (90 M; 51 F) admitted consecutively to the Unit with median age 54 years (range 15-68 years) with median length of stay 13.6 weeks (range 3-35 weeks). RESULTS: Ninety subjects (64%) gained from two to six points; 50 subjects (35%) gained one point or showed no change. One patient deteriorated by two points. Excluding patients admitted with the highest score (FIM level 7), the overall level of agreement between predicted and discharge scores was moderate (weighted kappa 0.47). Prediction was accurate to +/- 1 point in 113 subjects (80%). Overprediction by > or = 2 points occurred in 16 subjects (11%) and underprediction by > or = 2 points in 12 subjects (9%). Analysis of the most-disabled cohort, admitted with FIM levels 1 or 2 scores, revealed a higher sensitivity for predicting 'independence' (FIM levels 5-7) (78%) than 'dependence' (FIM levels 1-4) (65%). Accuracy was not affected by age, gender or side of stroke. Inaccurate predictions were associated with lower admission FIM level scores (p = -0.26; p = 0.002) and a greater length of stay (p = 0.36; p < 0.001). Subjects with quadriplegia were more likely to have inaccurate outcome predictions made than those with hemiplegia (p = 0.025) and those with neglect were more likely to have inaccurate outcome predictions made than those without neglect (p = 0.017). CONCLUSION: Further investigation into clinical prediction and the variables which confound accuracy is needed for effective planning.

Information and involvement.

This article discusses the beliefs that provision of good quality information is the key to (a) successful and satisfying involvement of patients in their own decision-making and (b) involvement of lay people in the research process, in debate and other involvement in wider health issues. Education of children, health professionals, the public and the media is advocated, enabling critical appraisal skills and good quality health information to lead to improved involvement of citizens in health-care decisions of all kinds, both individual and societal. Examples of individual, group and specific group involvement through research projects, debates about screening, Citizens' Juries, etc. are used to illustrate benefits to patients and to health provision in general.

The effect of a hinged ankle foot orthosis on hemiplegic gait: objective measures and users' opinions.

OBJECTIVE: To assess the effect of a hinged ankle foot orthosis (AFO) on functional mobility and gait impairments in people with a severe hemiplegia undergoing rehabilitation, and to investigate the patients' views of the hinged AFO. DESIGN: With/without group comparison, and face-to-face questionnaire. SUBJECTS AND SETTING: Twenty-five subjects over 18 years, with a hemiplegia following cerebrovascular accident (CVA) undergoing rehabilitation in a regional rehabilitation unit. OUTCOME MEASURES: Functional Ambulation Categories as a measure of disability. Paper walkways to measure gait impairments--stride length, step length, symmetry, cadence and velocity. Face-to-face questionnaire to determine the users' opinion of the hinged AFO. RESULTS: Comparison of gait with and without the hinged AFO showed significant improvements in functional mobility (p = 0.000) and in some gait impairments; stride length of the weak (p < 0.005, 95% CI -8.1, -1.6) and sound legs (p < 0.014, 95% CI -8, -1), velocity (p = 0.00, 95% CI -0.1, -0.03) and cadence (p < 0.002, 95% CI -15.1, -3.8). No effect was found for step length in the weak or sound leg or symmetry. The subjects' response was positive, 24 (96%) felt they walked better with the AFO and found it comfortable. Twenty-three (92%) were unbothered by the appearance and 16 (64%) could doff and don it. CONCLUSION: The hinged AFO improved objective measures of gait impairments and disability and patients were positive about it.

Can young severely disabled stroke patients regain the ability to walk independently more than three months post stroke?

OBJECTIVE: To investigate the acquisition of ability to walk independently in young severely disabled stroke patients unable to walk three months after onset. SETTING: A regional rehabilitation unit providing post-acute neurorehabilitation mainly for patients aged 16-65 years. SUBJECTS AND METHODS: A retrospective analysis of records was undertaken for 152 stroke patients admitted consecutively over a three-year period. All had a combination of physical, cognitive and language impairments; male/female 98/54; median age 54 (IQR 47-60) years. MAIN OUTCOME MEASURES: Time taken from stroke onset to regain the ability to walk safely and independently at least 5 metres around the hospital bay. RESULTS: Seventy-five (49%) regained the ability to walk independently between 3 and 11 months post onset. Patients with cognitive impairments and neglect took longer to walk. Time from stroke onset to admission was longer in patients who did not walk (median 16.3 weeks), than in those who regained walking (median 12.7 weeks; p = 0.009). Independent positive associations were found between the time taken to walk and time from onset to referral for rehabilitation (p = 0.55; p < 0.001), and time from acceptance to admission (p = 0.30; p = 0.008). CONCLUSION: With intensive specialist input, significant numbers of severely disabled young stroke patients can regain independent walking many months after onset, though late walkers may follow a slower recovery course. These results argue for investment in appropriate rehabilitation for these patients. Waiting list delays may prolong rehabilitation and potentially compromise cost effectiveness.