Ethnic minorities and prescription medication; concordance between self-reports and medical records

BACKGROUND: Ethnic differences in health care utilisation are frequently reported in research. Little is known about the concordance between different methods of data collection among ethnic minorities. The aim of this study was to examine to which extent ethnic differences between self-reported data and data based on electronic medical records (EMR) from general practitioners (GPs) might be a validity issue or reflect a lower compliance among minority groups. METHODS: A cross-sectional, national representative general practice study, using EMR data from 195 GPs. The study population consisted of Dutch, Turks, Surinamese, Antilleans and Morrocans. Self-reported data were collected through face-to-face interviews and could be linked to the EMR of GPs. The main outcome measures were the level of agreement between annual prescribing rate based on the EMRs of GPs and the self-reported receipt and use of prescriptions during the preceding 14 days. RESULTS: The pattern of ethnic differences in receipt and use of prescription medication depended on whether self-reported data or EMR data were used. Ethnic differences based on self-reports were not consistently reflected in EMR data. The percentage of agreement above chance between EMR data and self-reported receipt was in general relative low. CONCLUSION: Ethnic differences between self-reported data and EMR data might not be fully perceived as a cross-cultural validity issue. At least for Moroccans and Turks, compliance with the prescribed medication by the GP is suggested not to be optimal

Reproducibility and responsiveness of the Symptom Severity Scale and the hand and finger function subscale of the Dutch arthritis impact measurement scales (Dutch-AIMS2-HFF) in primary care patients with wrist or hand problems

BACKGROUND: To determine the clinimetric properties of two questionnaires assessing symptoms (Symptom Severity Scale) and physical functioning (hand and finger function subscale of the AIMS2) in a Dutch primary care population. METHODS: The first 84 participants in a 1-year follow-up study on the diagnosis and prognosis of hand and wrist problems completed the Symptom Severity Scale and the hand and finger function subscale of the Dutch-AIMS2 twice within 1 to 2 weeks. The data were used to assess test-retest reliability (ICC) and smallest detectable change (SDC, based on the standard error of measurement (SEM)). To assess responsiveness, changes in scores between baseline and the 3 month follow-up were related to an external criterion to estimate the minimal important change (MIC). We calculated the group size needed to detect the MIC beyond measurement error. RESULTS: The ICC for the Symptom Severity Scale was 0.68 (95% CI: 0.54–0.78). The SDC was 1.00 at individual level and 0.11 at group level, both on a 5-point scale. The MIC was 0.23, exceeding the SDC at group level. The group size required to detect a MIC beyond measurement error was 19 for the Symptom Severity Scale. The ICC for the hand and finger function subscale of the Dutch-AIMS2 was 0.62 (95% CI: 0.47–0.74). The SDC was 3.80 at individual level and 0.42 at group level, both on an 11-point scale. The MIC was 0.31, which was less than the SDC at group level. The group size required to detect a MIC beyond measurement error was 150. CONCLUSION: In our heterogeneous primary care population the Symptom Severity Scale was found to be a suitable instrument to assess the severity of symptoms, whereas the hand and finger function subscale of the Dutch-AIMS2 was less suitable for the measurement of physical functioning in patients with hand and wrist problems

Common ADRB2 Haplotypes Derived from 26 Polymorphic Sites Direct β2-Adrenergic Receptor Expression and Regulation Phenotypes

The beta2-adrenergic receptor (beta2AR) is expressed on numerous cell-types including airway smooth muscle cells and cardiomyocytes. Drugs (agonists or antagonists) acting at these receptors for treatment of asthma, chronic obstructive pulmonary disease, and heart failure show substantial interindividual variability in response. The ADRB2 gene is polymorphic in noncoding and coding regions, but virtually all ADRB2 association studies have utilized the two common nonsynonymous coding SNPs, often reaching discrepant conclusions.We constructed the 8 common ADRB2 haplotypes derived from 26 polymorphisms in the promoter, 5'UTR, coding, and 3'UTR of the intronless ADRB2 gene. These were cloned into an expression construct lacking a vector-based promoter, so that beta2AR expression was driven by its promoter, and steady state expression could be modified by polymorphisms throughout ADRB2 within a haplotype. "Whole-gene" transfections were performed with COS-7 cells and revealed 4 haplotypes with increased cell surface beta2AR protein expression compared to the others. Agonist-promoted downregulation of beta2AR protein expression was also haplotype-dependent, and was found to be increased for 2 haplotypes. A phylogenetic tree of the haplotypes was derived and annotated by cellular phenotypes, revealing a pattern potentially driven by expression.Thus for obstructive lung disease, the initial bronchodilator response from intermittent administration of beta-agonist may be influenced by certain beta2AR haplotypes (expression phenotypes), while other haplotypes may influence tachyphylaxis during the response to chronic therapy (downregulation phenotypes). An ideal clinical outcome of high expression and less downregulation was found for two haplotypes. Haplotypes may also affect heart failure antagonist therapy, where beta2AR increase inotropy and are anti-apoptotic. The haplotype-specific expression and regulation phenotypes found in this transfection-based system suggest that the density of genetic information in the form of these haplotypes, or haplotype-clusters with similar phenotypes can potentially provide greater discrimination of phenotype in human disease and pharmacogenomic association studies

The clinical global impression scale and the influence of patient or staff perspective on outcome

<p>Abstract</p> <p>Background</p> <p>Since its first publication, the Clinical Global Impression Scale (CGI) has become one of the most widely used assessment instruments in psychiatry. Although some conflicting data has been presented, studies investigating the CGI's validity have only rarely been conducted so far. It is unclear whether the improvement index CGI-I or a difference score of the severity index CGI-S_difis more valid in depicting clinical change. The current study examined the validity of these two measures and investigated whether therapists' CGI ratings correspond to the view the patients themselves have on their condition.</p> <p>Methods</p> <p>Thirty-one inpatients of a German psychotherapeutic hospital suffering from a major depressive disorder (age M = 45.3, SD = 17.2; 58.1% women) participated. Patients filled in the Beck Depression Inventory (BDI). CGI-S and CGI-I were rated from three perspectives: the treating therapist (THER), the team of therapists involved in the patient's treatment (TEAM), and the patient (PAT). BDI and CGI-S were filled in at admission and discharge, CGI-I at discharge only. Data was analysed using effect sizes, Spearman's <it>ρ </it>and intra-class correlations (ICC).</p> <p>Results</p> <p>Effect sizes between CGI-I and CGI-S _difratings were large for all three perspectives with substantially higher change scores on CGI-I than on CGI-S _dif. BDI_difcorrelated moderately with PAT ratings, but did not correlate significantly with TEAM or THER ratings. Congruence between CGI-ratings from the three perspectives was low for CGI-S _dif(ICC = .37; Confidence Interval [CI] .15 to .59; <it>F</it>_30,60= 2.77, <it>p </it>< .001; mean <it>ρ </it>= 0.36) and moderate for CGI-I (ICC = .65 (CI .47 to .80; <it>F</it>_30,60= 6.61, <it>p </it>< .001; mean <it>ρ </it>= 0.59).</p> <p>Conclusions</p> <p>Results do not suggest a definite recommendation for whether CGI-I or CGI-S _difshould be used since no strong evidence for the validity of neither of them could be found. As congruence between CGI ratings from patients' and staff's perspective was not convincing it cannot be assumed that CGI THER or TEAM ratings fully represent the view of the patient on the severity of his impairment. Thus, we advocate for the incorporation of multiple self- and clinician-reported scales into the design of clinical trials in addition to CGI in order to gain further insight into CGI's relation to the patients' perspective.</p

Three dimensional evaluation of posture in standing with the PosturePrint: an intra- and inter-examiner reliability study

Abstract Background Few digitizers can measure the complexity of upright human postural displacements in six degrees of freedom of the head, rib cage, and pelvis. Methods In a University laboratory, three examiners performed delayed repeated postural measurements on forty subjects over two days. Three digital photographs (left lateral, AP, right lateral) of each of 40 volunteer participants were obtained, twice, by three examiners. Examiners placed 13 markers on the subjects before photography and chose 16 points on the photographic images. Using the PosturePrint® internet computer system, head, rib cage, and pelvic postures were calculated as rotations (Rx, Ry, Rz) in degrees and translations (Tx, Tz) in millimeters. For reliability, two different types (liberal = ICC3,1 & conservative = ICC2,1) of inter- and intra-examiner correlation coefficients (ICC) were calculated. Standard error of measurements (SEM) and mean absolute differences within and between observers' measurements were also determined. Results All of the "liberal" ICCs were in the excellent range (> 0.84). For the more "conservative" type ICCs, four Inter-examiner ICCs were in the interval (0.5–0.6), 10 ICCs were in the interval (0.61–0.74), and the remainder were greater than 0.75. SEMs were 2.7° or less for all rotations and 5.9 mm or less for all translations. Mean absolute differences within examiners and between examiners were 3.5° or less for all rotations and 8.4 mm or less for all translations. Conclusion For the PosturePrint® system, the combined inter-examiner and intra-examiner correlation coefficients were in the good (14/44) and excellent (30/44) ranges. SEMs and mean absolute differences within and between examiners' measurements were small. Thus, this posture digitizer is reliable for clinical use

Risk factors and myocardial infarction in patients with obstructive sleep apnea: impact of β2-adrenergic receptor polymorphisms

BACKGROUND: The increased sympathetic nervous activity in patients with obstructive sleep apnea (OSA) is largely responsible for the high prevalence of arterial hypertension, and it is suggested to adversely affect triglyceride and high-density lipoprotein (HDL) cholesterol levels in these patients. The functionally relevant polymorphisms of the β2-adrenergic receptor (Arg-47Cys/Arg16Gly and Gln27Glu) have been shown to exert modifying effects on these risk factors in previous studies, but results are inconsistent. METHODS: We investigated a group of 429 patients (55 ± 10.7 years; 361 men, 68 women) with moderate to severe obstructive sleep apnea (apnea/hypopnea index (AHI) 29.1 ± 23.1/h) and, on average, a high cardiovascular risk profile (body mass index 31.1 ± 5.6, with hypertension in 60.1%, dyslipidemia in 49.2%, and diabetes in 17.2% of patients). We typed the β2-adrenergic receptor polymorphisms and investigated the five most frequent haplotypes for their modifying effects on OSA-induced changes in blood pressure, heart rate, and lipid levels. The prevalence of cardiovascular risk factors and coronary heart disease (n = 55, 12.8%) and survived myocardial infarction (n = 27, 6.3%) were compared between the genotypes and haplotypes. RESULTS: Multivariate linear/logistic regressions revealed a significant and independent (from BMI, age, sex, presence of diabetes, use of antidiabetic, lipid-lowering, and antihypertensive medication) influence of AHI on daytime systolic and diastolic blood pressure, heart rate, prevalence of hypertension, and triglyceride and HDL levels. The β2-adrenergic receptor genotypes and haplotypes showed no modifying effects on these relationships or on the prevalence of dyslipidemia, diabetes, and coronary heart disease, yet, for all three polymorphisms, heterozygous carriers had a significantly lower relative risk for myocardial infarction (Arg-47Cys: n = 195, odds ratio (OR) = 0.32, P = 0.012; Arg16Gly: n = 197, OR = 0.39, P = 0.031; Gln27Glu: OR = 0.37, P = 0.023). Carriers of the most frequent haplotype (n = 113) (haplotype 1; heterozygous for all three polymorphisms) showed a five-fold lower prevalence of survived myocardial infarction (OR = 0.21, P = 0.023). CONCLUSION: Our study showed no significant modifying effect of the functionally relevant β2-adrenergic receptor polymorphisms on OSA-induced blood pressure, heart rate, or lipid changes. Nevertheless, heterozygosity of these polymorphisms is associated with a lower prevalence of survived myocardial infarction in this group with, on average, a high cardiovascular risk profile

Agonist-Directed Desensitization of the β2-Adrenergic Receptor

The β2-adrenergic receptor (β2AR) agonists with reduced tachyphylaxis may offer new therapeutic agents with improved tolerance profile. However, receptor desensitization assays are often inferred at the single signaling molecule level, thus ligand-directed desensitization is poorly understood. Here we report a label-free biosensor whole cell assay with microfluidics to determine ligand-directed desensitization of the β2AR. Together with mechanistic deconvolution using small molecule inhibitors, the receptor desensitization and resensitization patterns under the short-term agonist exposure manifested the long-acting agonism of salmeterol, and differentiated the mechanisms of agonist-directed desensitization between a full agonist epinephrine and a partial agonist pindolol. This study reveals the cellular mechanisms of agonist-selective β2AR desensitization at the whole cell level

Unpredictable environments lead to the evolution of parental neglect in birds

A nest of begging chicks invites an intuitive explanation: needy chicks want to be fed and parents want to feed them. Surprisingly, however, in a quarter of species studied, parents ignore begging chicks. Furthermore, parents in some species even neglect smaller chicks that beg more, and preferentially feed the biggest chicks that beg less. This extreme variation across species, which contradicts predictions from theory, represents a major outstanding problem for the study of animal signalling. We analyse parent–offspring communication across 143 bird species, and show that this variation correlates with ecological differences. In predictable and good environments, chicks in worse condition beg more, and parents preferentially feed those chicks. In unpredictable and poor environments, parents pay less attention to begging, and instead rely on size cues or structural signals of quality. Overall, these results show how ecological variation can lead to different signalling systems being evolutionarily stable in different species

Polymorphisms in the ADRB2 gene and Graves disease: a case-control study and a meta-analysis of available evidence

<p>Abstract</p> <p>Background</p> <p>The beta-2-Adrenergic receptor (<it>ADRB2</it>) gene on chromosome 5q33.1 is an important immunoregulatory factor. We and others have previously implicated chromosomal region 5q31-33 for contribution to the genetic susceptibility to Graves disease (GD) in East-Asian populations. Two recent studies showed associations between the single nucleotide polymorphism (SNP) rs1042714 in the <it>ADRB2 </it>gene and GD. In this study, we aimed to fully investigate whether the <it>ADRB2 </it>gene conferred susceptibility to GD in Chinese population, and to perform a meta-analysis of association between <it>ADRB2 </it>and GD.</p> <p>Methods</p> <p>Approximately 1 kb upstream the transcription start site and the entire coding regions of the <it>ADRB2 </it>gene were resequenced in 48 Han Chinese individuals to determine the linkage disequilibrium (LD) patterns. Tag SNPs were selected and genotyped in a case-control collection of 1,118 South Han Chinese subjects, which included 428 GD patients and 690 control subjects. A meta-analysis was performed with the data obtained in the present samples and those available from prior studies.</p> <p>Results</p> <p>Fifteen SNPs in the <it>ADRB2 </it>gene were identified by resequencing and one SNP was novel. Ten tag SNPs were investigated further to assess association of <it>ADRB2 </it>in the case-control collection. Neither individual tag SNP nor haplotypes showed association with GD in Han Chinese population (P > 0.05). Our meta-analysis of the <it>ADRB2 </it>SNP rs1042714 measured heterogeneity between the ethnic groups (I²= 53.1%) and no association to GD was observed in the overall three studies with a random effects model (OR = 1.13, 95% CI, 0.95 to 1.36; P = 0.18). However, significant association was found from the combined data of Caucasian population with a fixed effects model (OR = 1.18, 95% CI, 1.06 to 1.32; P = 0.002; I²= 5.9%).</p> <p>Conclusion</p> <p>Our study indicated that the <it>ADRB2 </it>gene did not exert a substantial influence on GD susceptibility in Han Chinese population, but contributed to a detectable GD risk in Caucasian population. This inconsistency resulted largely from between-ethnicity heterogeneity.</p

Airway smooth muscle relaxation results from a reduction in the frequency of Ca(2+ )oscillations induced by a cAMP-mediated inhibition of the IP(3 )receptor

BACKGROUND: It has been shown that the contractile state of airway smooth muscle cells (SMCs) in response to agonists is determined by the frequency of Ca(2+ )oscillations occurring within the SMCs. Therefore, we hypothesized that the relaxation of airway SMCs induced by agents that increase cAMP results from the down-regulation or slowing of the frequency of the Ca(2+ )oscillations. METHODS: The effects of isoproterenol (ISO), forskolin (FSK) and 8-bromo-cAMP on the relaxation and Ca(2+ )signaling of airway SMCs contracted with methacholine (MCh) was investigated in murine lung slices with phase-contrast and laser scanning microscopy. RESULTS: All three cAMP-elevating agents simultaneously induced a reduction in the frequency of Ca(2+ )oscillations within the SMCs and the relaxation of contracted airways. The decrease in the Ca(2+ )oscillation frequency correlated with the extent of airway relaxation and was concentration-dependent. The mechanism by which cAMP reduced the frequency of the Ca(2+ )oscillations was investigated. Elevated cAMP did not affect the re-filling rate of the internal Ca(2+ )stores after emptying by repetitive exposure to 20 mM caffeine. Neither did elevated cAMP limit the Ca(2+ )available to stimulate contraction because an elevation of intracellular Ca(2+ )concentration induced by exposure to a Ca(2+ )ionophore (ionomycin) or by photolysis of caged-Ca(2+ )did not reverse the effect of cAMP. Similar results were obtained with iberiotoxin, a blocker of Ca(2+)-activated K(+ )channels, which would be expected to increase Ca(2+ )influx and contraction. By contrast, the photolysis of caged-IP(3 )in the presence of agonist, to further elevate the intracellular IP(3 )concentration, reversed the slowing of the frequency of the Ca(2+ )oscillations and relaxation of the airway induced by FSK. This result implied that the sensitivity of the IP(3)R to IP(3 )was reduced by FSK and this was supported by the reduced ability of IP(3 )to release Ca(2+ )in SMCs in the presence of FSK. CONCLUSION: These results indicate that the relaxant effect of cAMP-elevating agents on airway SMCs is achieved by decreasing the Ca(2+ )oscillation frequency by reducing internal Ca(2+ )release through IP(3 )receptors