Promoting clinically effective practice: general practitioners' awareness of sources of research evidence

BACKGROUND: Practitioners are being encouraged to base their clinical practice on research evidence. In order to do this, they must be aware of and use the sources of evidence. METHODS: A questionnaire survey was undertaken to establish GPs' awareness of research evidence in their clinical practice and, in fundholding practices, its influence on purchasing plans. Questionnaires were sent to 360 lead fundholders in North Thames Region and 440 of a random sample of the remaining general practitioners in the region for comparison. RESULTS: Questionnaires were returned by 62% of lead fundholders and 63% of GPs in the random sample. There was limited use of the electronic sources of clinical effectiveness. There was greater reported awareness of published sources of research evidence and fundholding GPs were significantly more likely to have referred to publications summarizing research evidence. CONCLUSIONS: GPs seem to make more use of published clinical effectiveness sources than the electronic databases. Consequently, they need educational and technical support if they are to make full use of the available sources of research evidence available in other media.      

Enhanced tyrosine phosphorylation of striatal NMDA receptor subunits: effect of dopaminergic denervation and l-DOPA administration

Sensitization of striatal N-methyl- -aspartate receptors (NMDAR) has been linked to events leading to the motor response changes associated with the administration of dopaminomimetics to parkinsonian animals and patients. To determine whether tyrosine phosphorylation of NMDAR subunits contributes to the apparent long-term enhancement in synaptic efficacy of these receptors, we examined the effect of unilateral nigrostriatal dopamine system ablation with 6-hydroxydopamine followed by twice-daily treatment with -DOPA on the phosphorylation state of rat striatal NR2A and NR2B subunits. Three weeks of intermittent -DOPA administration produced a shortening in the duration of the rotational response to dopaminergic challenge and other changes mimicking those occurring in patients with Parkinson's disease. Concurrently, tyrosine phosphorylation of NR2A and especially of NR2B subunits increased ipsilateral to the lesion (20±5% and 46±7% of intact striatum, respectively; p<0.01) without attendant changes in subunit protein levels. Selective blockade of NR2B subunits with ACEA 10-1244, but not of NR2A subunits with MDL 100,453, reversed the -DOPA-induced response alterations. The intrastriatal injection of a tyrosine kinase inhibitor, genistein, at a dose (2.0 μg) that normalized the response shortening, attenuated the NR2A and NR2B phosphorylation increase by about 12% and 24%, respectively (p<0.01). Taken together, these results suggest that augmented tyrosine phosphorylation of NR2B subunits, alone or in combination with the smaller rise in NR2A subunit phosphorylation, contributes to the apparent enhancement in striatal NMDAR sensitivity and thus to the plastic alterations in dopaminergic responses in -DOPA-treated parkinsonian rats.     

Genetic determinants of statin intolerance

Background  

Statin-related skeletal muscle disorders range from benign myalgias – such as non-specific muscle aches or joint pains without elevated serum creatinine kinase (CK) concentration – to true myositis with >10-fold elevation of serum CK, to rhabdomyolysis and myoglobinuria. The genetic basis of statin-related muscle disorders is largely unknown. Because mutations in the COQ2 gene are associated with severe inherited myopathy, we hypothesized that common, mild genetic variation in COQ2 would be associated with inter-individual variation in statin intolerance. We studied 133 subjects who developed myopathy on statin monotherapy and 158 matched controls who tolerated statins without incident or complaint.     

Bilateral versus unilateral sudden sensorineural hearing loss.

OBJECTIVES: To analyze the clinical characteristics and treatment results between bilateral (bi-) and unilateral (uni-) sudden sensorineural hearing loss (SSNHL). STUDY DESIGN AND SETTING: A retrospective study. METHODS: Three hundred twenty-four patients with SSNHL were classified into two groups; simultaneous bi-SSNHL (n = 16) and uni-SSNHL (n = 308). We compared clinical characteristics, medical history, hearing level, and treatment results between the 2 groups. RESULTS: The incidence of bi-SSNHL was 4.9 percent of overall patients with SSNHL. Bi-SSNHL occurs more commonly in patients of older age, with preexisting diabetes mellitus, and lipid panel abnormalities compared with uni-SSNHL. Ten patients (62.5%) in the bi-SSNHL group showed hearing recovery in 1 or both ears compared with 56.5 percent of patients with uni-SSNHL. Only 12 (37.5%) of all 32 ears recovered in bi-SSNHL, which was significantly lower than in uni-SSNHL. CONCLUSION: Bi-SSNHL has a very low incidence and lower recovery rate than uni-SSNHL. Recognition of similarities and differences between bilateral and unilateral SSNHL can help in counseling and managing the patients.     

Disturbances of bone growth and development

"What is growth anyway? Can one talk about positive growth in childhood, neutral growth in maturity, and negative growth in old age?" Our goal is to help promote normal positive growth in infants and children. To achieve this, we must be cognizant of the morphologic changes of both normal and abnormal bone formation as they are reflected in the radiographic image of the skeleton. The knowledge of the various causes and the pathophysiologic mechanisms of the disturbances of bone growth and development allows us to recognize the early radiographic manifestations. Endocrine and metabolic disorders affect the whole skeleton, but the early changes are best seen in the distal ends of the femurs, where growth rate is most rapid. In skeletal infections and in some vascular injuries two-or three-phase bone scintigraphy supercedes radiography early in the course of the disease. MRI has proved to be very helpful in the early detection of avascular bone necrosis, osteomyelitis, and tumor. Some benign bone tumors and many bone dysplasias have distinct and diagnostic radiographic findings that may preclude further studies. In constitutional diseases of bone, including chromosomal aberrations, skeletal surveys of the patient and all family members together with biochemical and cytogenetic studies are essential for both diagnosis and genetic counseling. Our role is to perform the least invasive and most informative diagnostic imaging modalities that corroborate the biochemical and histologic findings to establish the definitive diagnosis. Unrecognized, misdiagnosed, or improperly treated disturbance of bone growth can result in permanent deformity usually associated with disability.