Tackling the written paper.
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Education, Medical, Graduate↗
Biomedical subjects
Andrew Wilson
Publications and source records attributed to Andrew Wilson.
The inter-observer agreement of examining pre-school children with acute cough: a nested study.
BACKGROUND: The presence of clinical signs have implications for diagnosis, prognosis and treatment. Therefore, the aim of this study was to examine the inter-observer agreement of clinical signs in pre-school children presenting to primary care. METHODS: A nested study comparing two clinical assessments within a prospective cohort of 256 pre-school children with acute cough recruited from eight general practices in Leicestershire, UK. We examined agreement (using kappa statistics) between unstandardised and standardised clinical assessments of tachypnoea, chest signs and fever. RESULTS: Kappa values were poor or fair for all clinical signs (range 0.12 to 0.39) with chest signs the most reliable. CONCLUSIONS: Primary care clinicians should be aware that clinical signs may be unreliable when making diagnosis, prognosis and treatment decisions in pre-school children with cough. Future research should aim to further our understanding of how best to identify abnormal clinical signs.
Acute Disease↗
Predicting complications from acute cough in pre-school children in primary care: a prospective cohort study.
BACKGROUND: There is uncertainty about which children with cough are most and least likely to experience complications. AIM: To derive a clinical prediction rule for complications in pre-school children presenting to primary care with acute cough. DESIGN OF STUDY: Prospective cohort study. SETTING: Eight general practices in Leicestershire, United Kingdom. METHOD: Pre-school children with cough for < or =28 days and without asthma were recruited. Sociodemographic, clinical history, and examination data were collected and univariable logistic regression used to explore the associations with complications. These were defined as any new symptom, sign or diagnosis identified by a primary care clinician at a parent initiated reconsultation, or hospital admission, before cough resolution. Those factors with stronger relationships (P< 0.2) were then modelled using multivariable logistic regression to identify the factors independently associated with complications. RESULTS: The pre-test probability of complications was 10%. On univariable analysis, fever (odds ratio [OR] = 4.86; 95% confidence interval [CI] = 1.74 to 13.6), chest signs (OR = 2.72; CI = 1.06 to 6.96), and tachypnoea (OR = 3.80; CI = 1.22 to 11.8) were associated with complications. On multivariable analysis, only fever (OR = 5.56; CI = 1.75 to 17.6) and chest signs (OR = 2.88; CI = 1.02 to 8.05) were independently associated with complications. These ORs translate into post-test probabilities of complications of 6% for children with neither fever nor chest signs, 18% for children with chest signs, 28% for children with fever, and 40% for children with fever and chest signs. CONCLUSIONS: If validated, this clinical prediction rule could be used to individualise the management of acute cough in pre-school children.
Acute Disease↗
The use of infrared thermometry for the detection of fever.
The use of tympanic thermometry is attractive in primary care, but a recent systematic review highlighted the paucity of data comparing tympanic thermometry with conventional methods. We report a study of 94 preschool children presenting to primary care in the United Kingdom (UK) with acute cough in whom tympanic infrared and axillary mercury thermometry are compared. Infrared thermometry showed poor agreement, poor sensitivity and high specificity. Infrared thermometry is too insensitive to be used as a screening test for fever, but when fever is already suspected, for example by touch, it may be useful as a 'rule in' test.
Axilla↗
Clozapine inhibits isolated N-methyl-D-aspartate receptors expressed in xenopus oocytes in a subunit specific manner.
Antipsychotic agents have typically been viewed as acting through dopaminergic targets, although mounting evidence suggests that drugs such as clozapine may act on glutamatergic systems. In order to explore the effects of clozapine on the NMDA class of glutamate receptors, oocytes expressing the NMDA receptor NR1 subunit, coupled with different NR2 subunits, were exposed to clozapine and NMDA induced current was measured with two electrode voltage-clamp techniques. Our results indicate that clozapine inhibits the NMDA receptor, but that this inhibition is subunit specific, being significantly greater for receptors containing NR2A and NR2B than for those containing NR2C. Interestingly, the inhibition required pretreatment with clozapine before activation of the receptor with NMDA. In addition to providing mechanistic insights, this finding may help to explain divergent results in the literature regarding the effects of antipsychotic agents on glutamate receptors.
Animals↗
Reduced arterial elasticity in rheumatoid arthritis and the relationship to vascular disease risk factors and inflammation.
OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased rates of cardiovascular disease. Reduced small artery elasticity (SAE) and large artery elasticity (LAE) and increased systemic vascular resistance (SVR) have been found in other high-risk groups. In the present study, we sought to determine whether arterial elasticity was reduced and SVR was increased in RA patients compared with controls matched for coronary artery disease (CAD) status, and to relate the results to vascular disease risk factors, including measures of inflammation. METHODS: Arterial elasticity was assessed by pulse wave analysis in RA patients with (n = 15) and without (n = 38) CAD, and in controls matched 1:1 for age, sex, and CAD status. Vascular risk factors, including high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule 1 (sVCAM-1), and serum amyloid A (SAA) levels, were assessed. RESULTS: SAE and LAE were significantly lower and SVR was significantly higher in RA patients than in controls. RA patients also had higher levels of hsCRP, SAA, and sVCAM-1. SAE and LAE values were inversely correlated with markers of inflammation. Associations of SAE and LAE with RA were independent of conventional risk factors, but were dependent on markers of inflammation. CONCLUSION: Vascular function is abnormal in RA, with reduced SAE and LAE and increased SVR relative to controls. Arterial elasticity is inversely associated with measures of inflammation. These measures may be clinically useful in the detection and monitoring of vascular disease in RA.
Aged↗
Providing a seamless service for children with life-limiting illness: experiences and recommendations of professional staff at the Diana Princess of Wales Children's Community Service.
The Diana Children's Community Teams (DCCTs), a new nurse-led service funded by the Department of Health, were established to provide care in the community as an alternative to hospital for children with life-threatening/life-limiting illnesses and their families. This paper presents selected findings highlighting the professionals' experiences which formed part of the evaluation of the Diana, Princess of Wales Children's Community Service in Leicester, Leicestershire and Rutland. The Diana Service in Leicestershire attempts to encompass both parental empowerment and interagency collaboration. By working in partnership with the children and their families, the team provides an integrated and multiprofessional community-based service. This paper particularly concentrates on the perceptions and recommendations from the Diana team itself. Three independently managed Community Nursing Services existed in Leicestershire prior to the Diana teams; a Paediatric Macmillan Service, a Children's Community Nursing Service and a Respite Service. The Leicestershire DCCT integrated the three nursing services into a single team. This team has moved away from a traditional uniprofessional service structure by encompassing a wider team of multiprofessionals, including a cultural link worker, an occupational therapist, a physiotherapist, a play specialist and a team of trained counsellors, working in partnership to provide a quality service for families. * The evaluation, which used a longitudinal multimethod process analysis based on an action research framework, suggests that children with complex and life-limiting illnesses and their families benefit greatly from an effective seamless service. This paper recommends a framework of care that may be relevant to other teams of children's community services across the country. This service has been judged by the impact it has had on the families who use it and the professionals employed within it.
Catastrophic Illness↗
Coronary artery stent thrombosis associated with exercise testing.
Chest pain following coronary artery stenting is common, yet finding the cause can be difficult. Exercise testing has long been used in the assessment of chest pain, but its usefulness in patients who have recently undergone coronary artery stenting is in doubt. A case of exercise testing appearing to precipitate acute stent thrombosis in a patient several weeks post-coronary artery stenting is reported and compared to a similar case in the literature. The role of exercise testing in the assessment of chest pain early after coronary artery stenting is then reviewed.
Journal Article↗
The use and effectiveness of an emergency department observation unit for elderly patients.
STUDY OBJECTIVE: Emergency department observation units are cost-effective alternatives to hospital admission for selected patients. However, the use and effectiveness of these units in the elderly population is unclear. We sought to describe the use of an ED observation unit by elderly patients (>or=65 years), to determine whether the ED observation unit is effective for them in terms of ED observation unit length of stay and hospital admission rates, and to compare efficacy and return visit rates between younger and older patients. METHODS: This is a retrospective observational cohort study of consecutive adult patients sent to an ED observation unit from 1996 to 2000 at a high-volume tertiary care suburban teaching hospital. ED observation unit length of stay of less than 18 hours and admittance rates of less than 30% were used as indicators of efficacy. Diagnosis, length of stay, hospital admission rates, and 30-day return visit rates were compared between younger and older patients. RESULTS: Twenty-two thousand five hundred and thirty adult patients were observed, with 37.2% older than 65 years of age. The most common diagnoses in elderly patients were chest pain (24.0%), dehydration (11.7%), syncope (6.5%), back pain (4.6%), and chronic obstructive pulmonary disease (3.8%). Length of stay in the ED observation unit was longer for the elderly than younger patients but still averaged less than 18 hours (15.8 hours [95% confidence interval (CI) 15.7 to 16.0] versus 14.4 hours [95% CI 14.3 to 14.5], respectively). Elderly patients were more likely to be admitted from the ED observation unit than younger patients (26.1% versus 18.5%); however, their overall admission rate remained less than 30%. Compared with younger patients, the odds ratios for inpatient admission of elderly patients was highest for back pain (2.10; 95% CI 1.62 to 2.73), pyelonephritis (1.78; 95% CI 1.16 to 2.71), and chest pain (1.65; 95% CI 1.44 to 1.89). Thirty-day related return visit rates between age groups were similar (9.4% versus 7.6%). CONCLUSION: Elderly ED observation unit patients had ED observation unit lengths of stay and hospital admission rates that were effective for an ED observation unit setting and ED return visits rates that were comparable with those of younger patients.
Adult↗
Discussion of NRT and other antismoking interventions in UK general practitioners' routine consultations.
Nicotine replacement therapy (NRT) is an effective smoking cessation treatment, but little information is available about how primary care physicians use the therapy. We investigated the quality of UK general practitioners' (GPs') advice against smoking, including how frequently they recommend NRT to smokers. We compared the characteristics of smokers whom GPs recommended use NRT with smokers who did not receive GP recommendations. We conducted a cross-sectional survey of 3,525 adult patients attending 35 UK GPs over a 16-month period. Of those surveyed, 2,955 eligible patients (83.8%) completed preconsultation questionnaires, and 1,026 (34.7%) were regular smokers, with 927 (90.4%) of the regular smokers completing postconsultation questionnaires. Of those completing the questionnaires, 20.2% (95% CI, 17.7% to 22.9%) or 187 recalled discussion of smoking with their GPs and of these, 66.3% (95% CI, 60.1% to 74.1%) or 124 perceived that they had been given an unequivocal message to stop smoking. Although 60.4% of smokers (606 of 1,004) (95% CI, 57.3% to 63.3%) or smoked more than 10 cigarettes daily, only 17.6% (95% CI, 12.9% to 23.7%) or 33 of those recalling antismoking advice reported discussion of NRT. Accordingly, GPs discussed NRT with only a minority of smokers who might benefit from the therapy. Intending to give up smoking in the next 4 weeks was the only variable independently associated with smokers' recall of discussing NRT (OR=2.58 [95% CI 1.20% to 5.57%]). The study findings thus provide only limited information to support the notion that UK GPs recommend NRT in an evidence-based manner. Now that NRT is available by prescription from UK GPs, further research is needed to monitor whether this effective antismoking therapy is being prescribed appropriately.
Administration, Cutaneous↗
Comparison of the smoking behaviour and attitudes of smokers who believe they have smoking-related problems with those who do not.
BACKGROUND: Motivation to stop smoking is associated with smokers' possessing substantial smoking-related morbidity or believing that they have symptoms caused by smoking, but it is not clear if this holds for smokers attending general practice consultations. OBJECTIVE: Our aim was to compare the attitudes and behaviour of smokers attending their GP with symptoms that they believe are smoking related with those who do not. METHOD: A cross-sectional, pre-consultation survey of patients attending GPs in Leicester, UK was carried out. RESULTS: A total of 83.8% (2955/3525) of people attending GPs completed the questionnaire and 34.7% were smokers. Multiple logistic regression showed that where smokers perceived that their problems were smoking related they were more likely to have tried stopping in the past [odds ratio (OR) 1.78, 95% confidence interval (CI) 1.26-2.67], to want to stop smoking (OR 1.83, CI 1.15-2.9) or to intend to stop in the near future (OR 1.58, CI 1.03-2.43). CONCLUSION: Smokers who attend GPs' routine consultations and believe that they have smoking-related problems are more motivated to stop than others. This suggests that it is important for GPs to ascertain patients' views about the aetiology of their symptoms before discussing smoking with them.
Adult↗
The duration of acute cough in pre-school children presenting to primary care: a prospective cohort study.
BACKGROUND: Professional and parental uncertainty about the natural history of cough in pre-school children may in part be responsible for the high consultation and reconsultation rates and widespread antibiotic use in primary care. A recent systematic review of the natural history of cough included studies of unrepresentative, selected patients with heterogeneous measures and definitions of cough duration. OBJECTIVES: The aim of the present study was to describe the post-consultation duration of cough, compare this with clinician and parental prediction of cough duration, and to determine the clinical factors associated with prolonged cough. METHODS: A prospective cohort study of children aged 0-4 years with cough < or =28 days without asthma presenting to eight general practices in Leicestershire, UK was carried out. Socio-demographic and clinical data were collected, and parents and clinicians were asked to predict the proportion recovering within 7, 14, 21 and 28 days. Parents used a symptom diary to record cough and five other symptoms. Survival analysis was used to describe cough duration, and multivariable Cox regression was used to identify the factors independently associated with prolonged cough. RESULTS: Fifty percent of the children had recovered at 10 days and 90% at 25 days. Cough was associated with fever, breathlessness, disrupted sleep and reduced activity in a high proportion of children. Longer post-consultation cough was associated with longer pre-consultation cough and use of day care facilities. Clinicians overestimated how quickly children recovered from acute cough. Parents' predictions were accurate within 2 weeks, but they underestimated the proportion recovering in weeks 3 and 4. CONCLUSIONS: Clinicians should be aware that from the parental perspective, acute cough is not a trivial illness and that some children remain unwell at 3-4 weeks. For health professionals negotiating the use of antibiotics, this information may enable parental self-care, reduce medicalization and displace the need to prescribe.
Child, Preschool↗
Application of gene expression profiling to colon cell maturation, transformation and chemoprevention.
Methods for high-throughput analysis of profiles of gene expression that assay thousands of genes simultaneously are powerful approaches for understanding and classifying cell and tissue phenotype. This includes analysis of normal pathways of cell maturation and their perturbation in transformation, the sensitivity and mechanism of response of normal and tumor cells to physiological and pharmacological agents, and modulation of tumor risk and progression by nutritional factors. However, the complex data generated by such approaches raise difficulties in analysis. We will describe some of the methods we have used in analyzing databases generated in a number of projects in our laboratories. These include: the role of k-ras mutations in colon cell transformation; the role of p21(WAF1/cip1) in intestinal tumor formation and response to sulindac; the development of the absorptive and goblet cell lineages; sensitivity of colonic cells to chemotherapeutic agents; mechanisms that regulate c-myc expression utilizing novel methods of transcriptional imaging; and interaction of nutritional and genetic factors in modulation of intestinal tumor formation.
Animals↗
Performance of hospital-at-home after a randomised controlled trial.
OBJECTIVE: To compare the performance of an admission-avoidance hospital-at-home scheme one year after the end of a randomised trial with its performance during the trial. METHODS: Observational study of patients admitted to the scheme during a period of 12-19 months after the trial ended. In addition to routine data from service records, patients were interviewed at three days, two weeks and three months after admission, using the same instruments as used in the trial. RESULTS: All 78 patients admitted to hospital-at-home during the follow-up period were included, and compared with the 95 patients admitted during the trial. The referral rate to hospital-at-home was the same (11 per month) as during the trial. During the trial, patients were randomised to hospital-at-home or hospital, meaning that hospital-at-home worked at about double the trial volume in the post-trial period. Baseline characteristics showed no statistically significant differences except that post-trial patients were less cognitively impaired. There were no statistically significant differences between the groups in survival at two weeks and three months, or in Barthel index, Sickness Impact Profile 68 and Philadelphia Geriatric Morale Scale. Length of stay in hospital-at-home was significantly shorter in the post-trial period (median of five days versus seven, P < 0.001), and more patients received a visit from their general practitioner during the period of admission (54% versus 38%, P = 0.04); otherwise there were no significant differences in process measures. CONCLUSION: Apart from working at higher volume and achieving a shorter length of stay, performance of the hospital-at-home scheme a year after the trial ended was little different from that reported during the trial. This is an example of an observational study providing evidence to support the generalisability of trial findings.
Aged↗
Evolving general practice consultation in Britain: issues of length and context.
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Family Practice↗
Research and development at the health and social care interface in primary care: a scoping exercise in one National Health Service region.
The present project aimed to identify research activity at the health and social care interface in primary care within one National Health Service region, and to determine levels of research capacity and support within social services. The study was commissioned by a primary care research network (PCRN) in order to assess opportunities to increase research capacity within social services. Data were collected in two phases from 61 managers, team leaders and senior practitioners in social care, and six public health representatives in health authorities, using telephone interviews and focus groups. The findings highlighted a lack of infrastructure and support for research and development in social care. However, many social care respondents wanted opportunities to develop research skills with healthcare colleagues. Despite poor support, many small-scale projects were described, and many respondents showed an enthusiasm for engaging with research. Methods in use included surveys, action research, needs analysis and evaluation of service developments. Many examples of user involvement were given. Interface projects were usually instigated by interagency forums and funded from multiple sources. Most project work was motivated by service improvement or development, rather than aiming to produce generalisable knowledge. Barriers to conducting research included lack of confidence, research skills and time, as well as workload demands, lack of cover to release staff for research and lack of supervision. Research was not seen as legitimate work in some social care environments or as part of a career path. Existing joint working initiatives (such as the National Service Frameworks) were highlighted as flashpoints for potential research and evaluation activity. The findings suggest clear opportunities for PCRNs to develop research capacity at the interface with social care; for example, by signposting available resources, providing training grants and secondments for social care staff, and supporting interagency networks with a focus on evaluation. In turn, experience in promoting user involvement in social services could add value to research expertise at the primary care-social care interface.
Cooperative Behavior↗
A new method for describing smokers' consulting behaviours which indicate their motivation to stop smoking: an exploration of validity and reliability.
BACKGROUND: Smokers vary in their readiness to try stopping smoking, but there currently are no objective tools for identifying smokers' consulting behaviours which indicate their level of motivation to try stopping smoking. OBJECTIVE: The aim of this study was to investigate the construct validity and inter-observer reliability of the Smokers' Motivation Code (SMC). METHODS: General practice consultations between 29 different Leicestershire GPs and their patients were video-recorded. In 47 consultations, regular or occasional smokers discussed smoking with their GPs and their consulting behaviour was coded using the SMC. The reliability of three different observers' codings was investigated. Construct validity was also investigated by comparing smokers' consulting behaviours coded using the SMC with measures of motivation to stop smoking recorded on pre-consultation questionnaires. RESULTS: Two pairs of observers achieved good reliability when using the SMC to code smokers' consulting behaviours during a subset of 11 video-recorded consultations. For readiness behaviours (indicating motivation to stop smoking), kappas were 0.82 and 0.65, and for resistance behaviours (indicating little motivation to stop smoking), kappas were 0.74 and 1.0. For the 37 consultations attended by regular smokers, complete pre-consultation questionnaires were obtained. Smokers displaying readiness behaviours were significantly more likely than others to report having tried to stop in the past year, thinking about or trying to stop and to agree that their health would improve if they stopped smoking. Smokers displaying resistant behaviours were significantly less likely to report thinking about stopping/trying to stop smoking. CONCLUSION: We have provided some evidence to support the construct validity and inter-observer reliability of the SMC and have identified some consulting behaviours which might indicate smokers' motivation to stop smoking. Further work is needed to determine whether smokers' consulting behaviour can be used to predict future quit attempts.
Adult↗
Short chain fatty acids and colon cancer.
The development of intestinal cancer involves complex genetic and epigenetic alterations in the intestinal mucosa. The principal signaling pathway responsible for the initiation of tumor formation, the APC-beta-catenin-TCF4 pathway, regulates both cell proliferation and colonic cell differentiation, but many other intrinsic and extrinsic signals also modulate these cell maturation pathways. The challenge is to understand how signaling and cell maturation are also modulated by nutritional agents. Through gene expression profiling, we have gained insight into the mechanisms by which short chain fatty acids regulate these pathways and the differences in response of gene programs, and of the specific regulation of the c-myc gene, to physiological regulators of intestinal cell maturation, such as butyrate, compared with pharmacological regulators such as the nonsteroidal antiinflammatory drug sulindac. Moreover, we used a combination of gene expression profiling of the response of cells in culture to sulindac and the response of the human mucosa in subjects treated with sulindac for 1 month, coupled with a mouse genetic model approach, to identify the cyclin dependent kinase inhibitor p21(WAF1/Cip1) as an important suppressor of Apc-initiated intestinal tumor formation and a necessary component for tumor inhibition by sulindac. Finally, the mucous barrier, secreted by intestinal goblet cells, is the interface between the luminal contents and the intestinal mucosa. We generated a mouse genetic model with a targeted inactivation of the Muc2 gene that encodes the major intestinal mucin. These mice have no recognizable goblet cells due to the failure of cells to synthesize and store mucin. This leads to perturbations in intestinal crypt architecture, increased cellular proliferation and rates of cell migration, decreased apoptosis and development of adenomas and adenocarcinomas in the small and large intestine and the rectum.
Animals↗