(Correcting) misdiagnoses of asthma: A cost effectiveness analysis

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: The prevalence of physician-diagnosed-asthma has risen over the past three decades and misdiagnosis of asthma is potentially common. Objective: to determine whether a secondary-screening-program to establish a correct diagnosis of asthma in those who report a physician diagnosis of asthma is cost effective.Method: Randomly selected physician-diagnosed-asthmatic subjects from 8 Canadian cities were studied with an extensive diagnostic algorithm to rule-in, or rule-out, a correct diagnosis of asthma. Subjects in whom the diagnosis of asthma was excluded were followed up for 6-months and data on asthma medications and heath care utilization was obtained. Economic analysis was performed to estimate the incremental lifetime costs associated with secondary screening of previously diagnosed asthmatic subjects. Analysis was from the perspective of the Canadian healthcare system and is reported in Canadian dollars.Results: Of 540 randomly selected patients with physician diagnosed asthma 150 (28%; 95%CI 19-37%) did not have asthma when objectively studied. 71% of these misdiagnosed patients were on some asthma medications. Incorporating the incremental cost of secondary-screening for the diagnosis of asthma, we found that the average cost savings per 100 individuals screened was $35,141 (95$4,588-$69,278).Conclusion: Cost savings primarily resulted from lifetime costs of medication use averted in those who had been misdiagnosed.This work was funded by the Canadian Institute of Health Research, Canada and the University Of Ottawa Division Of Respiratory Medicine

The added value of C-reactive protein to clinical signs and symptoms in patients with obstructive airway disease: results of a diagnostic study in primary care

BACKGROUND: To evaluate the diagnostic accuracy of clinical signs and symptoms, C-reactive protein (CRP) and spirometric parameters and determine their interrelation in patients suspected to have an obstructive airway disease (OAD) in primary care. METHODS: In a cross sectional diagnostic study, 60 adult patients coming to the general practitioner (GP) for the first-time with complaints suspicious for obstructive airway disease (OAD) underwent spirometry. Peak expiratory flow (PEF)-variability within two weeks was determined in patients with inconspicuous spirometry. Structured medical histories were documented and CRP was measured. The reference standard was the Tiffeneau ratio (FEV(1)/VC) in spirometry and the PEF-variability. OAD was diagnosed when FEV(1)/VC ≤ 70% or PEF-variability > 20%. RESULTS: 37 (62%) patients had OAD. The best cut-off value for CRP was found at 2 mg/l with a diagnostic odds ratio (OR) of 4.4 (95% CI 1.4–13.8). Self-reported wheezing was significantly related with OAD (OR 3.4; CI 1.1–10.3), whereas coughing was inversely related (OR 0.2; CI 0.1–0.7). The diagnostic OR of CRP increased when combined with dyspnea (OR 8.5; 95% CI 1.7–42.3) or smoking history (OR 8.4; 95% CI 1.5–48.9). CRP (p = 0.004), FEV(1 )(p = 0.001) and FIV(1 )(p = 0.023) were related with the severity of dyspnea. CRP increased with the number of cigarettes, expressed in pack years (p = 0.001). CONCLUSION: The diagnostic accuracy of clinical signs and symptoms was low. The diagnostic accuracy of CRP improved in combination with dyspnea and smoking history. Due to their coherence with the severity of dyspnea and number of cigarettes respectively, CRP and spirometry might allow risk stratification of patients with OAD in primary care. Further studies need to be done to confirm these findings

A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11

We report the cloning of a gene, intronless in its coding region, which we have named APJ. This gene was cloned using the polymerase chain reaction (PCR), with a set of primers designed on the basis of the conservation that members of G protein-coupled receptors (GPCR) have in their transmembrane (TM) regions. The putative receptor protein, APJ, shares closest identity to the angiotensin receptor (AT1) ranging from 40 to 50% in the hydrophobic TM regions of these receptors. The transcripts for this gene were detected in many regions of the brain. PCR analysis of somatic cell lines found APJ-related sequences to be only present on chromosome 11, and high-resolution mapping by fluoresence in situ hybridization (FISH) sublocalized APJ on band q12.link_to_subscribed_fulltex

Cloning of human genes encoding novel G protein-coupled receptors

We report the isolation and characterization of several novel human genes encoding G protein-coupled receptors. Each of the receptors contained the familiar seven transmembrane topography and most closely resembled peptide binding receptors. Gene GPR1 encoded a receptor protein that is intronless in the coding region and that shared identity (43% in the transmembrane regions) with the opioid receptors. Northern blot analysis revealed that GPR1 transcripts were expressed in the human hippocampus, and the gene was localized to chromosome 15q21.6. Gene GPR2 encoded a protein that most closely resembled an interleukin-8 receptor (51% in the transmembrane regions), and this gene, not expressed in the six brain regions examined, was localized to chromosome 17q21.1-q21.3. A third gene, GPR3, showed identity (56% in the transmembrane regions) with a previously characterized cDNA clone from rat and was localized to chromosome 1p35-p36.1.link_to_subscribed_fulltex

Isolation of three novel human genes encoding G protein-coupled receptors

We have cloned and mapped the chromosomal location of three novel human genes encoding G protein-coupled receptors that we have named GPR6, GPR5, and GPR4. The entire coding region for each of these genes was contained on single exons. Gene GPR6 encoded a receptor that shared closest identity (71% in the transmembrane regions) with the human orphan receptor GPR3 and was localized to chromosome 6 (q21-q22.1). Northern blot analysis revealed that GPR6 transcripts were abundant in the human putamen and to a lesser extent in the frontal cortex, hippocampus, and hypothalamus. Gene GPR5 encoded a receptor that most closely resembled the orphan receptor RBS11 (48% in the transmembrane regions) and the MIP Iα/RANTES receptor (45% in the transmembrane regions) and was localized to chromosome 3 (p21.3-p21.1). Gene GPR4 shared identity (40% in the transmembrane regions) with the human platelet-activating factor receptor and was localized to chromosome 19 (q13.2-q13.3).link_to_subscribed_fulltex

Cloning and chromosomal mapping of three novel genes, GPR9, GPR10, and GPR14, encoding receptors related to interleukin 8, neuropeptide Y, and somatostatin receptors

We employed the polymerase chain reaction and genomic DNA library screening to clone novel human genes, GPR9 and GPR10, and a rat gene, GPR14. GPR9, GPR10, and GPR14 each encode G protein-coupled receptors. GPR10 and GPR14 are intronless within their coding regions, while GPR9 contains at least one intron. The receptor encoded by GPR9 shares the highest identity with human IL-8 receptor type B (38% overall and 53% in the transmembrane regions), followed by IL-8 receptor type A (36% overall and 51% in the transmembrane domains). GPR10 encodes a receptor that shares highest identity with the neuropeptide Y receptor (31% overall and 46% in the transmembrane domains). The receptor encoded by GPR14 shares highest identity with the somatostatin receptor SSTR 4 (27% overall and 41% in the transmembrane domains). Fluorescence in situ hybridization analysis localized GPR9 to chromosome 8p11.2-p12 and GPR10 to chromosome 10q25.3-q26.link_to_subscribed_fulltex

The cloning and chromosomal mapping of two novel human opioid- somatostatin-like receptor genes, GPR7 and GPR8, expressed in discrete areas of the brain

Following the cloning of the opioid receptors μ, κ, and δ, we conducted a search for related receptors. Using oligonucleotides based on the opioid and also the structurally related somatostatin receptors, we amplified genomic DNA using the polymerase chain reaction and isolated fragments of novel G protein-coupled receptor genes. Two of these gene fragments designated clones 12 and 11 were used to isolate the full-length genes. The intronless coding sequences of these genes, named GPR7 and GPR8, shared 70% identity with each other, and each shared significant similarity with the sequences encoding transmembrane regions of the opioid and somatostatin receptors. GPR7 was mapped to chromosome 10q11.2-q21.1 and GPR8 to chromosome 20q13.3. Northern blot analysis using human mRNA demonstrated expression of GPR7 mainly in cerebellum and frontal cortex, while GPR8 was located mainly in the frontal cortex. In situ hybridization revealed expression of GPR7 in the human pituitary. A partial sequence of the mouse orthologue of GPR7 was obtained, and in situ hybridization demonstrated expression in discrete nuclei of brain, namely suprachiasmatic, areuate, and ventromedial nuclei of hypothalamus. A stable cell line expressing the GPR7 gene was created, but expression levels of the receptor were low. The available pharmacology indicated binding to several opioid drugs such as bremazocine, levorphanol, and β-FNA, but not to the opioid receptor subtype-selective μ, δ, or κ agonists.link_to_subscribed_fulltex

Estudo comparativo entre o manejo da asma em uma unidade de referência da rede pública de Porto Alegre (RS) e as proposições do III Consenso Brasileiro no Manejo da Asma Asthma management in a public referral center in Porto Alegre in comparison with the guidelines established in the III Brazilian Consensus on Asthma Management

OBJETIVO: Avaliar se as diretrizes do III Consenso Brasileiro no Manejo da Asma estão sendo aplicadas em uma população de asmáticos em um hospital de referência da rede pública de Porto Alegre (RS). MÉTODOS: Todos os pacientes adultos que iniciaram tratamento entre 1999 e 2002 foram avaliados. O tratamento recebido foi classificado em concordante ou discordante do Consenso. As características clínicas da asma e a freqüência do tratamento por especialista foram comparadas entre os grupos. RESULTADOS: Foram avaliados os prontuários de 357 pacientes, com média de idade de 41 anos, sendo 106 homens (29,7%) e 251 mulheres (70,3%), 33 tabagistas (9,2%). O tratamento foi considerado discordante em 246 pacientes (70%), sendo que, neste grupo, houve ausência de tratamento com corticóide inalatório em pacientes com asma persistente em 174 deles (71%). Volume expiratório forçado no primeiro segundo normal, idade entre doze e dezoito anos e asma intermitente foram observados com maior freqüência entre os pacientes com tratamento concordante (p < 0,01). Tratamento discordante não teve correlação com tratamento por pneumologista, gravidade da asma persistente ou número de visitas à emergência. CONCLUSÃO: A maioria dos pacientes com asma tratados em uma unidade de referência da rede pública em Porto Alegre não faz o tratamento preconizado pelos consensos e o subtratamento com corticóide inalatório é a principal causa de discordância.<br>OBJECTIVE: To determine whether the guidelines put forth in the III Brazilian Consensus on Asthma Management are being applied in a population of asthma patients treated at a public hospital that is a referral center for asthma in the city of Porto Alegre, Brazil. METHODS: All adult asthma patients who began their treatment between 1999 and 2002 were evaluated. The treatment given was classified as consistent or inconsistent with the Consensus guidelines. The clinical features of asthma and the frequency of treatment provided by a specialist were compared between the two groups (those receiving guideline-consistent treatment and those receiving guideline-inconsistent treatment). RESULTS: The charts of 357 patients were evaluated. The study sample consisted of 106 males (29.9%) and 251 females (70.3%). The mean age was 41 years, and 33 (9.2%) of the patients were smokers. The treatment was considered inconsistent with the Consensus guidelines in 246 cases (70%). Of those 246, 174 (71%) had presented persistent asthma and were not treated with an inhaled corticosteroid. Normal forced expiratory volume in one second, being from 12 to 18 years of age, and having intermittent asthma were more frequently observed among the patients receiving guideline-consistent treatment (p < 0.01). No correlations were found between guideline-inconsistent treatment and being treated by a pulmonologist, severity of persistent asthma or number of emergency room visits. CONCLUSION: Most of the asthma patients treated at the public referral center in Porto Alegre did not receive treatment that was consistent with the Consensus guidelines. Undertreatment with inhaled corticosteroids was the principal source of that inconsistency