Senior house officer training. Impact of existing peer review visits needs to be increased.
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Biomedical subjects
Publications and source records attributed to P Little.
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OBJECTIVE: To assess three prescribing strategies for sore throat. DESIGN: Randomised follow up study. SETTING: 11 general practices in the South and West region. SUBJECTS: 716 patients aged 4 years and over with sore throat and an abnormal physical sign in the throat; 84% had tonsillitis or pharyngitis. Patients were randomised to three groups: prescription for antibiotics for 10 days (group 1,246 patients); no prescription (group 2,230 patients); or prescription for antibiotics if symptoms were not starting to settle after three days (group 3; 238 patients). MAIN OUTCOME MEASURES: Duration of symptoms; satisfaction and compliance with and perceived efficacy of antibiotics; time off school or work. Outcomes were documented in 582 subjects (81%). RESULTS: Median duration of antibiotic use differed significantly in the three groups (10 v 0 v 0 days, P < 0.001); 69% of patients in group 3 did not use their prescription. The proportion of patients better by day 3 did not differ significantly (37% v 35% v 30%, P = 0.28), nor did the duration of illness (median 4 v 5 v 5 days, P = 0.39), days off work or school (median 2 v 2 v 1, P = 0.13), or proportion of patients satisfied (96% v 90% v 93%, P = 0.09), although group 1 had fewer days of fever (median 1 v 2 v 2 days, P = 0.04). More patients in group 1 thought the antibiotics were effective (87% v 55% v 60%, P < 0.001) and intended coming to the doctor in future attacks (79% v 54% v 57%, P < 0.001). "Legitimation" of illness-to explain to work or school (60%) or family or friends (37%)-was an important reason for consultation. Patients who were more satisfied got better more quickly, and satisfaction related strongly to how well the doctor dealt with patient's concerns. CONCLUSION: Prescribing antibiotics for sore throat only marginally affects the resolution of symptoms but enhances belief in antibiotics and intention to consult in future when compared with the acceptable strategies of no prescription or delayed prescription. Psychosocial factors are important in the decision to see a general practitioner and in predicting the duration of illness.
Here we describe the cloning of the human Achaete Scute Homologue 2 (HASH2) gene, officially designated ASCL2 (Achaete Scute complex like 2), a homologue of the Drosophila Achaete and Scute genes. In mouse, this gene is imprinted and maps to chromosome 7. We mapped the human homologue close to IGF2 and H19 at 11p15.5, the human region syntenic with mouse chromosome 7, indicating that this imprinted region is highly conserved in mouse and man. HASH2 is expressed in the extravillus trophoblasts of the developing placenta only. The lack of HASH2 expression in non-malignant hydatidiform (androgenetic) moles indicates that HASH2 is also imprinted in man.
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OBJECTIVE: To compare general practitioners' reported management of acute back pain with 'evidence based' guidelines for its management. DESIGN: Confidential postal questionnaire. SETTING: One health district in the South and West region. SUBJECTS: 236 general practitioners; 166 (70%) responded. OUTCOME MEASURES: Examination routinely performed, 'danger' symptoms and signs warranting urgent referral, advice given, and satisfaction with management. RESULTS: A minority of general practitioners do not examine reflexes routinely (27%, 95% confidence interval 20% to 34%), and a majority do not examine routinely for muscle weakness or sensation. Although most would refer patients with danger signs, some would not seek urgent advice for saddle anaesthesia (6%, 3% to 11%), extensor plantar response (45%, 37% to 53%), or neurological signs at multiple levels (15%, 10% to 21%). A minority do not give advice about back exercises (42%, 34% to 49%), fitness (34%, 26% to 41%), or everyday activities. A minority performed manipulation (20%) or acupuncture (6%). One third rated their satisfaction with management of back pain as 4 out of 10 or less. CONCLUSIONS: The management of back pain by general practitioners does not match the guidelines, but there is little evidence from general practice for many of the recommendations, including routine examination, activity modification, educational advice, and back exercises. General practitioners need to be more aware of danger symptoms and of the benefits of early mobilisation and possibly of manipulation for persisting symptoms. Guidelines should reference each recommendation and discuss study methodology and the setting of evidence.
The Beckwith-Wiedemann syndrome (BWS) is an overgrowth malformation syndrome that occurs with an incidence of 1:13,700 births. There is a striking incidence of childhood tumors found in BWS patients. Various lines of investigation have localized "imprinted" genes involved in BWS and associated childhood tumors to 11p15. High resolution mapping of 8 rare balanced chromosomal BWS rearrangements enabled us to identify three distinct regions on chromosome 11p15 that might harbor genes involved in the above-mentioned disorders. These results suggest genetic heterogeneity that correlates with the clinical heterogeneity seen in the patients studied. Expressed candidate gene sequences from these regions have been cloned and partly sequenced. These transcripts are either disrupted by or are at least within a few kb of these BWS chromosome breakpoints. So far, zinc-finger sequences and one Kruppel-associated box (KRAB) domain were found in independent candidate genes which are compatible with a regulating function of growth promoting genes. The abundance of expression of these genes varies from low abundant in all adult and fetal tissues tested to detectable on Northern blots of adult tissues. In addition to our 11p15 studies we have analyzed additional chromosome regions, in particular 1p. Cytogenetic, loss of heterozygosity (LOH) and comparative genomic hybridization (CGH) studies have identified 1p35 as a region of interest. A positional cloning effort to identify a balanced 1p35 translocation found in a Wilms tumor has led to the isolation of a YAC, crossing this breakpoint.
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This paper discusses primary care management of sore throat in the context of recent national 'consensus' guidelines from the Drugs and Therapeutics Bulletin. The guidelines advise taking a throat swab, using typical clinical features where swabs are not available, and suggest that antibiotics shorten the duration of symptoms and prevent complications. Systematic reviews and individual studies indicate that the evidence for prescribing antibiotics for most presentations of sore throat in general practice is marginal, and the benefits are probably outweighed by the likely costs of antibiotics. Using clinical scorecards or symptom clusters to identify individuals who would benefit from treatment is insensitive with low predictive value, although inexpensive. Using throat swabs as a gold standard for diagnosis is inappropriate since they are neither very specific nor sensitive, and will greatly increase costs of management. The relative lack of evidence for the efficacy of antibiotics and for the use of throat swabs from primary care research, and also an unbalanced perspective of dangers and complications related predominantly to a secondary care setting, underlines the problem of achieving valid consensus guidelines. Guidelines not firmly based on evidence appropriate to the intended setting are more likely to be received sceptically and hinder getting research into practice.
BACKGROUND: Diet and physical activity are important in many conditions managed in primary care. Dietary and physical activity assessment is complex, has inherent inaccuracies related to self-reporting, and is only a small part of a larger context of developing effective intervention in primary care. However, for personalized assessment in routine clinical care, and for the assessment of different intervention strategies in a general practice research setting, validated life-style assessment tools are needed. OBJECTIVE: We aimed to discuss the requirements for assessment tools and to identify feasible validated assessment instruments for use in primary care. METHOD: Potential tools were identified from a Medline search, UK Research Intelligence, and contact with groups known to be working in the area. RESULTS: Several brief instruments assess mainly fat in the US diet, but the limited range of foods covered and the setting of studies limits their generalizability. Only one tool developed for UK use--'DINE', which scores total fat, fibre and unsaturated fat--was identified which is both feasible and has documented reasonable validated characteristics. Even for this tool there are doubts about the validation "standard'. No diet or physical activity validation studies have used both subjects and health professionals from general practice settings. CONCLUSION: There are very few feasible and validated dietary or physical activity assessment tools for use in clinical care or research in general practice, and doubts about the design and settings of published validation studies. Further research is needed to validate and develop a range of feasible life-style assessment tools with specified time and training requirements for use in primary care.
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Evidence from meta-analyses, physiological data and individual studies suggests that diet and exercise are important in the aetiology and treatment of many of the conditions that are managed predominantly in primary care (hypercholesterolaemia, hypertension, diabetes, obesity and excess alcohol intake). However, much of the evidence comes from outside primary care, and it is doubtful whether those studies done in primary care used optimal intervention strategies. A priority for future research should be to demonstrate the feasibility, efficacy and efficiency of lifestyle interventions in a general practice setting.
Beckwith-Wiedemann syndrome (BWS) involves fetal overgrowth and predisposition to a wide variety of embryonal tumors of childhood. We have previously found that BWS is genetically linked to 11p15 and that this same band shows loss of heterozygosity in the types of tumors to which children with BWS are susceptible. However, 11p15 contains > 20 megabases, and therefore, the BWS and tumor suppressor genes could be distinct. To determine the precise physical relationship between these loci, we isolated yeast artificial chromosomes, and cosmid libraries from them, within the region of loss of heterozygosity in embryonal tumors. Five germ-line balanced chromosomal rearrangement breakpoint sites from BWS patients, as well as a balanced chromosomal translocation breakpoint from a rhabdoid tumor, were isolated within a 295- to 320-kb cluster defined by a complete cosmid contig crossing these breakpoints. This breakpoint cluster terminated approximately 100 kb centromeric to the imprinted gene IGF2 and 100 kb telomeric to p57KIP2, an inhibitor of cyclin-dependent kinases, and was located within subchromosomal transferable fragments that suppressed the growth of embryonal tumor cells in genetic complementation experiments. We have identified 11 transcribed sequences in this BWS/tumor suppressor coincident region, one of which corresponded to p57KIP2. However, three additional BWS breakpoints were > 4 megabases centromeric to the other five breakpoints and were excluded from the tumor suppressor region defined by subchromosomal transferable fragments. Thus, multiple genetic loci define BWS and tumor suppression on 11p15.
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