Documenting asthma severity: do we get it right?

BACKGROUND: The 1997 National Asthma Education and Prevention Program (NAEPP) recommends a severity classification scheme to optimize the use of anti-inflammatory therapy for persistent asthma. Physician documentation of asthma severity is often used as a quality assurance measure. OBJECTIVE: To test the hypothesis that physician documentation of asthma severity is associated with appropriate use of anti-inflammatory therapy. DESIGN/METHODS: Setting: inner-city academic health center. First, we reviewed a consecutive sample of charts of scheduled pediatric patients. Then, we administered a structured parent survey regarding the child's asthma symptoms and current asthma therapy. We used NAEPP guidelines to classify patients' severity of asthma. The main outcome measure was appropriate use of anti-inflammatory therapy. Appropriate therapy was defined as: (1) mild persistent asthmatics using anti-inflammatory therapy, and (2) moderate-severe persistent asthmatics using inhaled steroids. Chart classification of asthma severity was compared with the NAEPP-applied classification. RESULTS: Of 784 charts, 214 (27%) were asthmatic. Of these, 176 (82%) were surveyed. The mean age was 7.4 years; 61% were males. Severity classification was documented in 77% of charts. Chart documentation differed significantly from survey classification for the same patients: (mild intermittent 54% vs. 40%, mild persistent 21% vs. 14%, moderate persistent 24% vs. 36%, severe persistent 1% vs. 10%; all p < .001). Correctly classified patients were more likely to be on appropriate therapy. CONCLUSIONS: Physicians underestimated the severity classification of asthmatic patients. Incorrect classification was associated with inappropriate asthma therapy. These findings have implications for the institution of asthma quality improvement programs.     

Diagnostic accuracy of the Retinal Thickness Analyser: differentiation between normal eyes and eyes with glaucoma or macular pathologies

Background The Retinal Thickness Analyser (RTA) is intended to detect glaucomatous changes as well as macular pathologies at the posterior pole. We determined the diagnostic accuracy for eyes with manifest glaucoma or macular diseases.Methods We examined 71 eyes with long-term, established eye conditions. Included were 28 eyes with glaucoma, 21 with different macular diseases and 22 normal eyes. All examinations were evaluated in a blind-test by RTA experts without any clinical information on the patients. After comparison of the RTA interpretation with the clinical diagnosis, we determined sensitivity, specificity, positive and negative predictive values.Results Of 71 examinations, 15 (21%) were not interpretable. If these results are excluded, the following diagnostic accuracy values were calculated for glaucoma and macular disorders respectively: sensitivity 75 and 59%, specificity 55 and 97%, positive predictive value 48 and 90% and negative predictive value 80 and 84%. These values were not significantly different when both eyes of each patient were included in the final analysis (n=133).Conclusion The diagnostic values of the RTA determined in this case control study were not satisfactory. However, no clinical information was used in the assessment. The extent to which additional clinical information increases the diagnostic value remains to be determined.     

Effects of acute administration of d-amphetamine and haloperidol on procedural learning in man

The effects of an indirect dopamine-agonist, d-amphetamine, and a non-selective dopamine receptor antagonist, haloperidol, were investigated in normal male volunteers using a between-subjects double-blind design in a procedural learning task, thought mainly to involve unconscious/automatic learning. The results showed: (1) d-amphetamine facilitated response speed, whereas haloperidol inhibited it, in comparison to placebo; (2) the linear increase in procedural learning corresponded with pharmacological manipulation of degree of dopaminergic activity, i.e. subjects given haloperidol showed the least, and subjects given d-amphetamine the greatest, procedural learning. The implications of these findings are discussed in relation to investigation of abnormalities of procedural learning processes in schizophrenia. Received: 28 June 1996/Final version: 2 October 1996     

Characterization of gp 50, a major glycoprotein present in rat brain synaptic membranes, with a monoclonal antibody

Several cell lines secreting monoclonal antibodies (Mabs) against a major forebrain synaptic membrane (SM) glycoprotein, gp 50, have been raised. Western blots show that the Mabs react with a polypeptide doublet of Mrs 49 and 45 kDa. These polypeptides exist solely in a concanavalin A (Con A) binding form. Removal of the Con A receptors by digestion with endo-beta-N-acetylglucosaminidase H (endo H) lowers the Mrs of the glycoprotein doublet to 36.5 and 34 kDa. Western blots of 2D polyacrylamide gels indicate that gp 50 exists in several isoforms. Solid phase radioimmunoassay (RIA) and Western blots of brain subcellular fractions show the antigenic material to be concentrated in the SM fraction, but to be present in much lower amounts in synaptic junctions and postsynaptic densities. Gp 50 appears to be brain specific. Regional distribution studies show that it is present in all brain regions but is two-fold concentrated in cerebellum, brainstem and midbrain compared to forebrain. Immunocytochemical studies of several brain regions show that gp 50-like immunoreactivity is neuron specific and is concentrated in selected neuronal species, particularly granule cells. In both cerebellar and hippocampal granule cells gp 50-like immunoreactivity is localized in the perikarya and primary dendrites. Though immunocytochemistry did not show staining of synaptic regions this may be due to masking of the reactive epitope. The results are discussed in terms of the molecular properties of gp 50 and its subcellular localization in brain tissue.     

Diacetyl-Induced Lung Disease

Diacetyl is a diketone flavouring agent that is commonly employed for buttery taste as well as other purposes. Industrial exposure to flavouring agents, particularly diacetyl, has recently been associated with bronchiolitis obliterans, a severe respiratory illness producing fibrosis and obstruction of the small airways. This has been most commonly reported in the microwave popcorn production industry, but it has occurred elsewhere. In addition to bronchiolitis obliterans, spirometry abnormalities (fixed airflow obstruction) and respiratory symptoms have been associated with exposure. A direct effect on the respiratory epithelium with the disorganised fibrotic repair appears most likely as the underlying mechanism. Current data suggest that diacetyl is the agent responsible, although it is possible that diacetyl is simply a marker for another causative agent.     

The bioethics of preterm labour

Until recently, bioethics (ethics related to biology or, more specifically, in the context of preterm labour, medical ethics) was considered mainly to relate to the active treatment or investigation of patients. Collection of data, excised specimens or even whole organs was considered to be relatively uncontentious as it did not impinge directly upon the health of the individual concerned. However, in the UK in particular, the practice of collecting data, tissues or even whole organs has recently come under the spotlight of public scrutiny, particularly following the Alder Hey Enquiry. Coincidentally with a decline in public confidence in the probity of authority, medical scientists increasingly have to justify the accumulation of data about individuals.     

Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.

Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.