Subtype-specific inherited predisposition to pemphigus in the Chinese population.

BACKGROUND: Pemphigus is a group of rare life-threatening mucocutaneous autoimmune diseases, presenting mainly as two subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Inherited predispositions to pemphigus have long been speculated but they remain poorly understood. OBJECTIVES: To identify common and specific nongenetic and genetic factors associated with pemphigus and its subtypes in the Chinese population. METHODS: A genome-wide association study (GWAS) was performed in 496 unrelated patients with pemphigus (including 365 with PV and 104 with PF) and 1105 controls without pemphigus. RESULTS: A sex preference was observed only in PV (57·5% female) and not in PF (47·1% female). For male patients only, the mean age at diagnosis was significantly lower for PV than for PF (P < 0·001). The strongest associated single-nucleotide polymorphisms are in the human leucocyte antigen (HLA) region: rs70993900 (PV; P = 1·5 × 10-45 ) and rs9469220 (PF; P = 1·1 × 10-8 ). HLA-DQB1*05:03 ranks at the top (P = 4·7 × 10-40 ; odds ratio 12·4) in both subtypes, with significantly different risk allele frequency (RAFPV = 34·2% vs. RAFPF = 18·8% vs. RAFcontrol = 4·4%), whereas HLA-DRB1*14:01 and HLA-DRB1*04:06 are PV specific. HLA-DQB1*03:03 and HLA-DQB1*03:02 show significant subtype specificity in opposite directions. All of these associations were validated in the replication series with 147 cases of pemphigus and 604 controls. Multiple novel non-HLA susceptibility loci were also identified in the GWAS. CONCLUSIONS: This study represents the largest GWAS on pemphigus in the Chinese population published to date, and has allowed us to identify HLA haplotypes significantly shared between or specific to the two main subtypes of pemphigus.

High tetramethylpyrazine production by the endophytic bacterial Bacillus subtilis isolated from the traditional medicinal plant Ligusticum chuanxiong Hort.

Tetramethylpyrazine (TMP) with significant protective effects on cardiovascular is the active ingredient of traditional Chinese medicine Rhizoma Chuanxiong (RC). However, many studies have reported the low content of TMP in RC. The endophytes of medicinal plants have the biosynthetic potential to produce the same or similar active metabolites as the host, while few reports were conducted to explore the endophytic bacteria of Ligusticum chuanxiong Hort. and its productive capacity for the important ingredient TMP. The present paper focuses on the isolation and identification of TMP producing endophytic bacteria from RC. In this study, the endophytic bacteria were isolated from the rhizome of Ligusticum chuanxiong Hort. (Umbelliferae). Yeast extract peptone glucose medium (YP) was used for fermentation medium (37 °C, 220 rpm agitation, 144 h). GC and GC/MS were performed to determine and verify the product, the fermentation characteristics were investigated. Morphological observation, physiological and biochemical indexes combining with 16S rRNA sequence analysis were carried out to identify the endophytic bacteria. As a result, five strains of endophytic Bacillus subtilis were firstly isolated and identified from RC, named as LB3, LB3-2-1, LB6-2, LB4, LB5 respectively. All five strains of endophytic B. subtilis produced TMP, while LB5 had the highest production of 10.69 g/L at the 144 h fermentation. This work demonstrates the fact that the endophytic B. subtilis of RC can produce a high level of TMP, indicating the endophytic B. subtilis might play a role in the accumulation of TMP during the growth period of RC.

Relationship between the flavonoid composition and flower colour variation in Victoria.

Victoria (Nymphaeaceae), an annual or perennial aquatic plant genus, contains only two species: V. amazonica (Poepp.) J. C. Sowerby and V. cruziana A. D. Orb. Both species have large floating leaves and variable flower colour. Both Victoria species are night bloomers, which have white petals on the first blooming night that then turn pink or ruby red on the second blooming day. The mechanism of the colour change of Victoria petals during anthesis is still unclear. In this study, flavonoids in Victoria petals of both species were evaluated and quantified by high-performance liquid chromatography with photodiode array detection (HPLC-DAD) and by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) for the first time. In total, 14 flavonoids were detected in Victoria petals, including 4 anthocyanins and 10 flavonols. The flavonoid compositions differed across the two species, resulting in different colours between the inner and outer petals. With increased anthocyanin content across blooming days, the colour of Victoria flowers changed over time. The results of this study will improve understanding of the chemical mechanism of colour formation and lay the foundation for selective colour breeding in Victoria.

The use of lncRNA analysis for stratification management of prognostic risk in patients with NSCLC.

OBJECTIVE: Lung cancer is the most frequent cancer in China and worldwide. Long noncoding RNAs (lncRNAs) have been shown to play important regulatory roles in human cancer biology. The aim of the present study was to investigate the relationship between genomics and prognosis among lung cancer patients. PATIENTS AND METHODS: We collected specimens from non-small cell lung cancer (NSCLC) patients after surgery. Q-PCR was performed to investigate the expression level of lncRNAs in cancerous and adjacent normal tissue. Patients were divided into different risk groups according to lncRNA expression levels and then follow-up. RESULTS: The lncRNAs HOTAIR, H19 and MALAT1 were up-regulated, while PANDAR and TUG1 were down-regulated in NSCLC cancer tissues compared with the corresponding adjacent normal tissue. After two years of follow-up time, the disease-free survival time (DFS) curves were significantly different between the high-risk, moderate-risk and low-risk patient groups. CONCLUSIONS: Our results suggest that lncRNAs are involved in the process of NSCLC and that the use of genetic analysis for stratification management of prognostic risk could help us to implement individualized treatment for patients with NSCLC and ultimately to improve the patient prognosis.

Low expression of long noncoding RNA PANDAR predicts a poor prognosis of non-small cell lung cancer and affects cell apoptosis by regulating Bcl-2.

Recently, a novel class of transcripts, long noncoding RNAs (lncRNAs), is involved in diseases including cancer. Here, we investigated the the role of lncRNA PANDAR in the progression of non-small cell lung carcinoma (NSCLC). PANDAR, interacting with NF-YA, was generally downregulated in NSCLC tissues. In a cohort of 140 NSCLC patients, decreased PANDAR expression was negatively correlated with greater tumor size (P<0.001) and advanced TNM stage (P=0.002). Moreover, PANDAR could serve as an independent predictor for overall survival in NSCLC (P=0.015). Further experiments demonstrated that PANDAR expression was induced by p53, and chromatin immunoprecipitation (ChIP) assays confirmed that PANDAR was a direct transcriptional target of p53 in NSCLC cells. PANDAR overexpression significantly repressed the proliferation in vitro and in vivo. We also showed that PANDAR-mediated growth regulation is in part due to the transcriptional modulation of Bcl-2 by interacting with NF-YA, thus affecting NSCLC cell apoptosis. To our knowledge, this is the first report which showed the role of PANDAR in the progression of NSCLC. The p53/PANDAR/NF-YA/Bcl-2 interaction might serve as targets for NSCLC diagnosis and therapy.

P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression.

Recently, a novel class of transcripts, long non-coding RNAs (lncRNAs), is being identified at a rapid pace. These RNAs have critical roles in diverse biological processes, including tumorigenesis. Here we report that taurine-upregulated gene 1 (TUG1), a 7.1-kb lncRNA, recruiting and binding to polycomb repressive complex 2 (PRC2), is generally downregulated in non-small cell lung carcinoma (NSCLC) tissues. In a cohort of 192 NSCLC patients, the lower expression of TUG1 was associated with a higher TNM stage and tumor size, as well as poorer overall survival (P<0.001). Univariate and multivariate analyses revealed that TUG1 expression serves as an independent predictor for overall survival (P<0.001). Further experiments revealed that TUG1 expression was induced by p53, and luciferase and chromatin immunoprecipitation (ChIP) assays confirmed that TUG1 was a direct transcriptional target of p53. TUG1 knockdown significantly promoted the proliferation in vitro and in vivo. Moreover, the lncRNA-mediated regulation of the expression of HOX genes in tumorigenesis and development has been recently receiving increased attention. Interestingly, inhibition of TUG1 could upregulate homeobox B7 (HOXB7) expression; ChIP assays demonstrated that the promoter of HOXB7 locus was bound by EZH2 (enhancer of zeste homolog 2), a key component of PRC2, and was H3K27 trimethylated. This TUG1-mediated growth regulation is in part due to specific modulation of HOXB7, thus participating in AKT and MAPK pathways. Together, these results suggest that p53-regulated TUG1 is a growth regulator, which acts in part through control of HOXB7. The p53/TUG1/PRC2/HOXB7 interaction might serve as targets for NSCLC diagnosis and therapy.

Impact of concurrent macrovascular co-morbidities on healthcare utilization in patients with type 2 diabetes in Europe: a matched study.

AIM: To examine and to quantify the impact of concurrent macrovascular co-morbidities (MVC) on healthcare resource utilization among patients with type 2 diabetes mellitus (T2DM) in Europe. METHODS: This is a matched cohort study based on the Real-Life Effectiveness and Care Patterns of Diabetes Management study, a multicentre, observational study with retrospective medical chart reviews of T2DM patients in Spain, France, UK, Norway, Finland, Germany and Poland. Included patients were aged > or =30 years at time of diagnosis of T2DM who added a sulfonylurea or a PPARgamma agonist to failing metformin monotherapy (index date) and had concurrent MVC (cases). A control cohort with T2DM but without concurrent MVC was identified using 1:1 propensity score matching. Logit models were used to identify the relationship between concurrent MVC and the likelihood of emergency room admission, receiving medical/surgical procedures, and hospitalization during the study period after controlling for baseline demographics, clinical information and baseline treatment. Negative binomial models were used to predict the number of office visits and length of hospital stay per year attributable to the concurrent MVC. RESULTS: Relative to controls, patients with MVC were significantly more likely to have emergency department admissions [odds ratio (OR) 2.69; 95% CI: 1.56-4.65], receiving medical/surgical procedures (OR 2.57; 95% CI: 1.56-4.21) and hospitalizations (OR 2.58; 95% CI: 1.64-4.07) after controlling for other predictors. Similarly, MVC were associated with 1.49 additional office visits per year (p = 0.036) and 0.32 days of hospital stay per year (p = 0.023). CONCLUSIONS: Within a seven-country European sample, this study showed that T2DM patients with MVC were more likely to use healthcare resources compared with T2DM patients without MVC.

Time to insulin treatment and factors associated with insulin prescription in Swedish patients with type 2 diabetes.

AIMS: The purpose of this study was to investigate the time between the start of OAD treatment and the initiation of insulin therapy and to identify the factors associated with insulin prescription among Swedish patients with type 2 diabetes in Uppsala County. METHODS: Retrospective, population-based, primary-care data gathered within the Swedish RECAP-DM study were used to identify type 2 diabetic patients who initiated OAD treatment. A Kaplan-Meier survival estimate for time to initiation of insulin therapy was generated and factors associated with insulin prescription were tested using a Cox proportional-hazards model. RESULTS: Within 6 years of starting OAD treatment, an estimated 25% of Swedish patients with type 2 diabetes will be prescribed insulin (95% CI: 0.23-0.26) and, within 10 years, this figure will rise to 42% (95% CI: 0.39-0.45). The probability of insulin prescription was increased in patients aged less than 65 years (HR=1.24, 95% CI: 1.03-1.50) and in those who initiated OAD treatment with more than one agent (HR=2.71, 95% CI: 2.15-3.43). HbA(1c) at the time of starting OAD treatment was also related to the probability of insulin prescription (HR=1.20, 95% CI: 1.146-1.25). CONCLUSION: Many type 2 diabetic patients who begin treatment with an OAD will eventually be prescribed insulin. Age, disease severity and the type of prior treatment may affect the rate of the transition.

Treatment choice and effectiveness of adding sulphonylurea or glitazones to metformin for the treatment of type 2 diabetes mellitus.

AIM: This study investigates the treatment choice between, and the effectiveness of, adding sulphonylurea or glitazone to ongoing metformin therapy for patients with type 2 diabetes mellitus in the clinical practice setting. METHODS: A multicentre observational study using data from clinical records was conducted in Finland, France, Germany, Norway, Poland, Spain and the UK. Data were collected for patients who added sulphonylurea or glitazone to metformin. Effectiveness was defined as a change in haemoglobin A1c (HbA(1c)) from baseline to approximately 1 year after the initiation of additional therapy. To allow for comparisons between the two medication regimens, propensity score matching was employed. Treatment choice was analysed using a probit regression model. We hypothesized that treatment choice was associated with factors reflecting patient's characteristics, patient's experience with diabetes, patient's health or to physician's characteristics at baseline. RESULTS: Compared with baseline, adding sulphonylurea to metformin reduced HbA(1c) by 0.8% (p < 0.0001), while adding glitazone to metformin reduced HbA(1c) by 0.9% (p < 0.0001). Percentage at HbA(1c) goal (6.5%) increased from 6.9 to 23.8% for the sulphonylurea group and 8.3 to 33.3% for the glitazone group. Both groups had similar changes in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides. In the probit regression model, age, HbA(1c), weight, treatment for weight reduction, history of macrovascular complications and type of physician were significant factors associated with treatment choice. CONCLUSIONS: This study is consistent with the results of long-term randomized clinical trials in a clinical practice setting. Both regimens were able to reduce HbA(1c) by about 1%.

Prevalence and incidence of Type 2 diabetes and its complications 1996-2003--estimates from a Swedish population-based study.

AIMS: To determine the prevalence and incidence of Type 2 diabetes and its complications in Uppsala county, Sweden between 1996 and 2003. METHODS: Retrospective population-based study of patients with Type 2 diabetes identified in computerized medical records at 26 county primary care centres. Prevalence and incidence of Type 2 diabetes were estimated in the population aged 30-39, 40-49, 50-59, 60-69, 70-79 and > or = 80 years. Mortality, prevalence and incidence of complications in patients with Type 2 diabetes were determined through linkage to national inpatient, uraemia and cause-of-death registers. RESULTS: Crude prevalence of Type 2 diabetes increased from 2.2 to 3.5% between 1996 and 2003. In the population aged > or = 30 years, the age- and sex-adjusted period increase was 53%[odds ratio (OR) 1.53, 95% confidence interval (CI) 1.47-1.58]. Crude population incidence was approximately stable after 1997 (3.7 cases/1000 residents in 1997 compared with 3.8/1000 in 2003). Age- and sex-adjusted mortality rates in Type 2 diabetic patients decreased by 4% per year (OR 0.96, 95% CI 0.94-0.97). Prevalence rates of cardiovascular disease in Type 2 diabetic patients were essentially stable, affecting 13.8% of females and 18.0% of males in 2003. No trend was detected for prevalence of renal failure or incidence of acute myocardial infarction, stroke and amputation. CONCLUSIONS: Prevalence of Type 2 diabetes increased in Uppsala county between 1996 and 2003 as a consequence of approximately stable incidence since 1997 and declining mortality. Rates of diabetes-related complications, notably cardiovascular disease, continued to impose a substantial burden.

Resource use and costs of type 2 diabetes in Sweden - estimates from population-based register data.

AIMS: To examine medical resource use of Swedish patients with type 2 diabetes during 2000-2004 and to estimate annual costs of care. METHODS: Retrospective population-based cohort study of patients with type 2 diabetes identified in computerised medical records at 26 primary care centres in Uppsala county, Sweden. Annual quantities of medical resources were determined for prevalent cases during 2000-2004 using register data from outpatient primary care, outpatient hospital care, the National Inpatient Register and a national register for treatment of uraemia. Average costs of care of patients with type 2 diabetes were estimated based on year 2004 resource quantities of 8230 prevalent study cases. RESULTS: Annual quantities of medical resource use were stable in outpatient primary care and outpatient hospital care, with patients making an average of two General Practitioner visits and 3.5 outpatient hospital visits each year. Higher rates of hospitalisation [12% in 2000 (n = 6711) compared with 16% in 2004 (n = 8230)] led to an increase in the mean (SD) number of inpatient days from 2.3 (11.8) to 2.7 (11.9) (p = 0.040) between 2000 and 2004. Mean (SD) total costs of care in 2004 were EUR 3602 (EUR 9537). Inpatient care was the major contributor to costs, accounting for 57% of total costs while drug costs accounted for an average 7%. CONCLUSIONS: Swedish type 2 diabetic patients in this large sample from Uppsala county required steady annual amounts of outpatient care and increasing amounts of inpatient care during 2000-2004. The associated costs in 2004 were substantial, with inpatient care identified as the most important component.

End-stage renal disease risk equations for Hong Kong Chinese patients with type 2 diabetes: Hong Kong Diabetes Registry.

AIMS/HYPOTHESIS: The objective of the study was to investigate risk factors and develop risk equations for end-stage renal disease (ESRD) in Chinese patients with type 2 diabetes. SUBJECTS AND METHODS: A prospective cohort of 4,438 patients with type 2 diabetes mellitus and without ESRD (median observation period 2.9 years, interquartile range 1.6-4.1 years) was included in the analysis. The end-point (ESRD) was defined by: (1) death due to diabetes with renal manifestations or renal failure; (2) hospitalisation due to renal failure; (3) estimated GFR (eGFR) <15 ml min(-1) 1.73 m(-2). Cox proportional hazards regression was used to develop risk equations. The data were randomly and evenly divided into the training data for development of the risk equations and the test data for validation. The validation was performed using the area under the receiver operating characteristic curve (aROC), which takes into account follow-up time and censoring. RESULTS: During the observation period, 159 patients or 12.45 per 1,000 person-years (95% CI 10.52-14.37 per 1,000 person-years) developed ESRD. Known duration of diabetes, systolic blood pressure, log(10) total cholesterol:HDL cholesterol ratio and retinopathy were significant predictors of ESRD. After further adjusting for eGFR, log(10) spot albumin:creatinine ratio (ACR) and haematocrit, only eGFR, haematocrit and log(10) ACR remained as independent predictors of ESRD. The risk equation derived from these three independent predictors had good discrimination, with an aROC of 0.97. CONCLUSIONS/INTERPRETATION: Estimated GFR, haematocrit and ACR were independent predictors of ESRD and the derived risk equation performed well in Chinese patients with type 2 diabetes.

Asthma-related resource use and cost by GINA classification of severity in three European countries.

BACKGROUND: This study assessed the relationship between asthma burden and asthma severity in France, Italy, and Spain. METHODS: Adult asthmatics, 18-55 years of age, completed a questionnaire while visiting a respiratory physician in 1998 and 1999. Asthma severity was categorized by physicians as intermittent, mild persistent, moderate persistent, or severe persistent according to Global Initiative for Asthma (GINA) guidelines. RESULTS: Totals of 282 patients in France, 500 in Italy, and 296 in Spain entered the study. There were few differences between the three countries in the asthma symptom burden. Most patients with persistent asthma had used inhaled corticosteroids in the previous 14 days. Unexpectedly, 35% (Italy) to 83% (Spain) of patients with intermittent asthma also had used inhaled corticosteroids. In Spain, visits to the emergency department were more frequent (OR 7.0, 95% CI 4.9-10.0 with Italy as reference) and the costs of emergency care in all asthma severity categories were up to 10 times higher than in Italy and France. The frequency of hospitalizations did not differ systematically between the three countries. CONCLUSIONS: Inadequate control of asthma symptoms among patients with severe persistent asthma could not be entirely explained by under-prescribing of asthma medications. The use of inhaled corticosteroids by patients with intermittent asthma might reflect misclassification of asthma severity, possibly due to difficulty in interpreting the GINA guidelines. The relatively high cost of emergency care in Spain does not appear to be related to greater asthma severity or poorer symptom control, but may be a feature of the Spanish health care system.

Increased risk of asthma attacks and emergency visits among asthma patients with allergic rhinitis: a subgroup analysis of the investigation of montelukast as a partner agent for complementary therapy [corrected].

BACKGROUND: Inadequately controlled allergic rhinitis (AR) in asthmatic patients can contribute towards increased asthma exacerbations and poorer symptom control, which may increase medical resource use. We assessed asthma-related medical resource use and attacks in asthmatic patients who did and did not have concomitant AR and were adding montelukast or salmeterol to baseline treatment with inhaled fluticasone. METHODS: A post hoc resource use analysis of a 52-week, double-blind multicentre clinical trial (Investigation of Montelukast as a Partner Agent for Complementary Therapy) [corrected] including 1490 adults with chronic asthma, aged 15-72 years, with FEV(1) 50-90% of predicted and > or =12% increase in FEV(1) after salbutamol administration, treated with either montelukast 10 mg daily or salmeterol 50 microg twice daily in addition to fluticasone 200 microg, was undertaken. Asthma-related medical resource use included medical visits (defined as either an unscheduled visit [to a general practitioner, a specialist or a non-medical provider] or a specialist visit), emergency room visits and hospitalizations during follow-up. Asthma attacks were defined as the worsening of asthma requiring unscheduled visit, emergency visit, hospitalization or oral/intravenous/intramuscular corticosteroids. RESULTS: A self-reported history of concomitant AR was identified in 60% of the patients (n=893). Univariate analysis suggests that significantly more patients with concomitant AR experienced emergency room visits (3.6% vs. 1.7%, P=0.029) and asthma attacks (21.3% vs. 17.1%, P=0.046). Multivariate analysis adjusting for treatment group, age and baseline asthma severity confirmed these results since the presence of concomitant AR in patients with asthma increases the likelihood of emergency room visit (odds ratio (OR)=2.35, 95% confidence interval (CI)=1.12-4.80) and asthma attack (OR=1.35, 95% CI=1.03-1.77). Patients with asthma alone compared with patients with both conditions did not differ in terms of unscheduled or specialist visits and hospitalizations. CONCLUSIONS: Presence of self-reported concomitant AR in patients with asthma resulted in a higher rate of asthma attacks and more emergency room visits compared with asthma patients without concomitant AR.

Effect of a concomitant diagnosis of allergic rhinitis on asthma-related health care use by adults.

BACKGROUND: Asthma and allergic rhinitis (AR) frequently coexist, but have usually been studied separately in health economic analyses. OBJECTIVE: To determine the incremental effect of documented AR on health care resource use in adults with asthma. METHODS: A retrospective cohort study using data from a UK general practice database for the period 1998-2001 enrolled subjects 16-55 years of age, with one or more asthma-related general practitioner (GP) visits during a 12-month follow-up period. The study outcomes were asthma-related hospitalizations, GP visits, and prescription drug costs during the 12-month follow-up period for patients with and without physician-diagnosed AR. RESULTS: Concomitant AR was documented in 4,611 (16.9%) of the total sample of 27,303 adults with asthma. Compared with those with asthma alone, patients with concomitant AR experienced more GP visits (5.2 vs. 4.2; P<0.0001) and more of them were hospitalized for asthma (0.76% vs. 0.45%; P<0.01) during the 12-month follow-up period. In multi-variable regression analyses, AR was predictive of hospitalization for asthma (odds ratio 1.52, 95% confidence interval (CI) 1.03-2.24) and was associated with an increase in the annual number of asthma-related GP visits (mean increase per patient 0.42, 95% CI 0.42-0.43) and annual asthma-related drug costs (mean increase GBP 5.1, 95% CI 5.0-5.3). CONCLUSION: Adults with asthma and documented concomitant AR experienced more asthma-related hospitalizations and GP visits, and incurred higher asthma drug costs than did adults with asthma alone. A unified treatment strategy for asthma and AR might reduce the costs of treating these conditions.

Association between allergic rhinitis and hospital resource use among asthmatic children in Norway.

BACKGROUND: Preliminary evidence suggests that inadequately controlled allergic rhinitis in asthmatic patients can contribute towards increased asthma exacerbations and poorer symptom control, which may increase medical resource use. The objective of this study was therefore to assess the effect of concomitant allergic rhinitis on asthma-related hospital resource utilization among children below 15 years of age with asthma in Norway. METHODS: A population-based retrospective cohort study of children (aged 0-14 years) with asthma was conducted using data from a patient-specific public national database of hospital admissions during a 2-year period, 1998-1999. Multivariate linear regression, adjusting for risk factors including age, gender, year of admission, urban/rural residence and severity of asthma episode, estimated the association between allergic rhinitis and total hospital days. A multivariate Cox proportional-hazards model estimated relative hazard of readmission according to concomitant allergic rhinitis status. RESULTS: Among 2961 asthmatic children under 15 years of age with at least one asthma-related hospital admission over a 2-year period, 795 (26.8%) had a recorded history of allergic rhinitis. Asthmatic children with allergic rhinitis had a 1.72-times greater hazard of asthma-related readmissions than asthmatic children without allergic rhinitis. Multivariate analysis revealed that history of concomitant allergic rhinitis was a significant predictor of increased number of hospital days per year (least-squares mean difference 0.23 days, P < 0.05). CONCLUSIONS: Concomitant allergic rhinitis in asthmatic children was associated with increased likelihood of asthma-related hospital readmissions and greater total hospital days.

Asthma severity and medical resource utilisation.

Asthma represents a growing public health problem and the cost of asthma has been rising in many countries. The aim of this study was to estimate the direct and indirect cost of asthma among adult patients in Italy, and to assess the relationship between healthcare resource use and asthma severity according to the Global Initiative for Asthma (GINA) classification system. A multicentre cross-sectional study was conducted in 16 Italian hospital-based specialised asthma clinics. Data collection was based on self-administered questionnaires and took place during the period May 1-November 30, 1999, and 500 consecutive patients with asthma, aged 18-55 yrs, were enrolled during regularly scheduled visits. Direct costs (drugs, physician visits, emergency service use and hospitalisation), indirect costs (loss of paid workdays) and total costs were determined in euros (Euros) for 1999. Patients with more severe disease, as classified by the GINA guideline, exhibited more night-time and daytime symptoms and were more limited in performing normal daily activities. The mean total cost of asthma per patient per year was estimated to be Euros 1,260; drug costs accounted for 16%, physician costs 12%, emergency service and hospitalisation costs 20% and indirect costs 52% of the mean cost. Stratified by severity, the total annual cost per patient amounted to Euros 720, Euros 1,046, Euros 1,535 and Euros 3,328 for patients with intermittent, mild persistent, moderate persistent and severe persistent asthma, respectively. Asthma severity, as determined by the Global Initiative for Asthma classification, is significantly associated with symptoms, limitations in normal daily activities, asthma-related medical resource utilisation and both direct and indirect costs. Asthma control is not only a clinical but also an economic imperative.

Cost of care for inpatients with community-acquired intra-abdominal infections.

Few studies have assessed the actual costs associated with failure of initial empiric antibiotic therapy administered to patients with community-acquired intra-abdominal infections. The goals of this study were (i) to determine the frequency of unsuccessful initial empiric therapy in a real-world setting and (ii) to determine the associated impact on medical costs. Thus, a retrospective chart review was performed at four acute-care university hospitals in France. A total of 292 patients hospitalized for community-acquired intra-abdominal infection were included. The mean age of the cohort was 51 years, and 42% of the patients were female. The most commonly administered empiric regimens were intravenous amoxicillin/clavulanate alone (69 patients) or in combination with other antibiotics ( n=87) and piperacillin/tazobactam alone ( n=24) or in combination ( n=48). Other regimens included broad-spectrum penicillin, cephalosporins, and fluoroquinolones administered alone or in combination ( n=64). Empiric therapy was successful in 189 (65%) patients and unsuccessful in 103 (35%). Among the 292 patients with community-acquired infection, 15 died of the infection, 8 required reoperation and 80 required second-line antibiotic therapy. Patients with unsuccessful initial empiric therapy had significantly more parenteral antibiotic days (10.3 vs. 7.6 days) and a longer length of stay (16.2 vs. 12.8 days) compared to those with successful initial empiric therapy. A better selection of initial empiric antibiotic therapy may significantly influence the medical costs associated with patients who are hospitalized with community-acquired intra-abdominal infections.

Economic costs of HIV infection: an employer's perspective.

The introduction of highly active antiretroviral therapy has proven highly effective in treating patients with HIV/AIDS. However, the high cost of the advanced antiretroviral therapy has led to increased financial constraints on both patients and payers. From business firms'perspective, especially those with operations in developing countries, it is crucial to determine the long-term economic cost implications of alternative employment and benefit policies for HIV-infected workers or those at high risk for the disease. A simulation model is developed to predict the comprehensive lifetime economic costs of HIV-infected workers to an employer. This model employs age,CD4(+) cell counts,and plasma HIV-1 RNA level as major predictors of the disease progression and patient survival in the determination of various cost functions. Major cost components considered include direct expenses on health insurance premium,life insurance premium, short-term disability benefits, long-term disability benefits, hiring/training expenses, and indirect costs resulting from reduced or lost productivity at work. An individual model and a group model are derived to estimate the costs of an individual and a group of HIV-infected patients, respectively. Over a 10-year period, following the nonadvanced antiretroviral treatment regimen, the group model predicts that the total lifetime cost of an HIV-infected worker can be as high as U.S. 90,000 dollars to his/her employer, of which 60,000 dollars would be various explicit costs and 30,000 dollars lost work productivity. Sensitivity analysis further demonstrated that changes in the initial level of age,CD4(+) cell count, HIV-1 RNA viral load,CD4(+) cell decline rate, and the costs of medical care influence the dynamics of the cost functions. HIV infection can result in sizable economic costs to an employer over the lifetime course of an infected employee if not treated with the advanced antiretroviral therapy. These cost estimates provide a rational economic basis for an employer to optimally assess the longrun costs and benefits of alternative employment and insurance policies in the care of employees with HIV infection.