bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival analysis and prognostic indicators of systemic lupus erythematosus in Pakistani patients
Authors: Rabbani MA , Habib HB , Islam M , Ahmad B , Majid S , Saeed W , Shah SMA , Ahmad A
Published: July 2009

To aim of this study is to analyse the survival rate and prognostic indicators of systemic lupus erythematosus (SLE) in Pakistani population. A total of 198 patients with SLE diagnosed between 1992 and 2005 were reviewed retrospectively. Clinical features at presentation, subsequent evolving features, autoantibody profile, damage scores and mortality data were obtained. Prognostic factors for survival were studied by statistical analysis. Of 198 SLE patients studied, 174 were women and 24 were men. The women to men ratio was 7.2:1. Mean age at presentation was 31 years (range 14–76). Mean duration of symptoms before diagnosis was 2.8 years. Mean duration of follow-up was 34.21 months (±33.69). Mean disease duration was 15.6 years. At diagnosis, arthritis, malar rash, oral ulcers and alopecia were the commonest features. During the follow-up, the prevalence of nephritis, arthritis, neurological and hematological disease increased significantly. About 76% ( n = 151) of the patients had organ damage at the time of data analysis, and renal disease was the commonest cause. Univariate analysis revealed that renal disease ( P = 0.000), seizures ( P = 0.048), pleural involvement ( P = 0.019), alopecia ( P = 0.000) and discoid lesions ( P = 0.005) were predictors for damage. Multivariate model, however, revealed that only renal disease was independent risk factor for damage ( P = 0.002). During the study period, 47 patients (24%) died (five due to disease-related complications and rest as a result of infections). The 3-, 5-, 10-, 15- and 20-year survival rates of our cohort were 99, 80, 77, 75 and 75%, respectively. Cox regression analysis revealed that renal involvement ( P = 0.002) and infections ( P = 0.004) were independent risk factors for mortality. The survival of our Pakistani SLE patients was significantly lower compared to that of the Caucasian series reported in last decade. Nephritis not only contributes to organ damage but also acts a major determinant for survival. Infection remains the commonest cause of death. Renal involvement and infections are independent risk factors for mortality. Judicious use of immunosuppressive agents is necessary to improve the short-term survival of lupus patients.
Adipocytokines in systemic lupus erythematosus: relationship to inflammation, insulin resistance and coronary atherosclerosis
Authors: Chung CP , Long AG , Solus JF , Rho YH , Oeser A , Raggi P , Stein CM
Published: July 2009

We tested the hypothesis that concentrations of adipocytokines are altered in SLE and associated with coronary atherosclerosis, insulin resistance and inflammation. Concentrations of resistin, leptin, adiponectin and visfatin were measured in 109 patients with SLE and 78 control subjects. Coronary calcification was measured using electron beam-computed tomography, and insulin resistance was defined by the homeostasis model assessment index. Concentrations of adiponectin (28.7 ± 17.9 vs 22.0 ± 15.3 μg/mL, P = 0.003), leptin (41.1 ± 49.9 vs 19.8 ± 24.6 ng/mL, P < 0.001) and visfatin (7.5 ± 10.5 vs 4.5 ± 2.8 ng/mL, P < 0.001) were higher in patients with SLE than in controls. These differences remained significant after adjustment for age, race, sex and body mass index (BMI; all P values < 0.02). Concentrations of resistin (10.7 ± 7.6 vs 9.1 ± 5.1 ng/mL, P = 0.41) did not differ in patients and controls. In patients with SLE, leptin was positively associated with BMI ( ρ = 0.80, P < 0.001), insulin resistance ( ρ = 0.46, P < 0.001) and C-reactive protein (CRP) ( ρ = 0.30, P = 0.002), whereas adiponectin was negatively associated with the same factors ( ρ = –0.40, P < 0.001; ρ = −0.38, P < 0.001; ρ = –0.22, P = 0.02, respectively). None of the adipocytokines were associated with coronary atherosclerosis in SLE. In conclusion, patients with SLE have increased concentrations of adiponectin, leptin and visfatin. Lower concentrations of adiponectin and higher concentrations of leptin are associated with insulin resistance, BMI and CRP in patients with SLE.
The causes and clinical significance of fever in systemic lupus erythematosus: a retrospective study of 487 hospitalised patients
Authors: Zhou WJ , Yang CD
Published: July 2009

The causes of fever in systemic lupus erythematosus (SLE) are complicated. Differential diagnosis of fever in SLE is crucial for optimal management of these patients. To better understand the causes and characteristics of fever in SLE, the medical records of 1949 consecutive patients hospitalised for SLE from January 2002 to May 2007 were reviewed. A total of 487 SLE-hospitalised patients with fever were identified and retrospectively analysed. Among them, 265 patients had fever from infection, 206 had fever related to SLE, 8 had fever caused by both SLE activity and infections, 4 had fever caused by malignancies and 4 had fever ascribed to miscellaneous causes. The most common sites of infection were the respiratory tract (62.6%), urinary tract (8.6%), skin and mucosa (8.3%). A prednisone dose of ≤100 mg/d was able to suppress SLE fever in 80.6% of the patients, usually within 1–5 days. Compared to patients with infection fever, those with SLE fever were more likely to have lower serum complement C3 and a higher SLE Disease Activity Index score. Infection fever was found to be associated with the use of azathioprine within the last six months. In conclusion, infection and disease activity are the most common causes of fever in SLE. Those patients for whom SLE fever could not be suppressed by a higher dose of steroids usually had severe lupus encephalopathy or hemophagocytic syndrome.
Long-term follow-up after non-myeloablative transplant of bone and marrow in BXSB mice
Authors: Jones OY , Lacson A , Zeng X , Jones JM , Katti K , Cahill RA , Ahmed AA
Published: July 2009

We present long-term outcomes of BXSB mice after non-myeloablative bone marrow transplants using major histocompatability complex (MHC)-matched cells. Groups differed in sources of donor lymphocytes or mesenchymal stromal cells (MSC). Unfractionated marrow cells from green fluorescent protein (GFP) transgenic (Tg) mice (BMT group) or from RAG1−/− B6 mice (RAG group) were injected intravenously (i.v.) into irradiated (550 cGy) hosts. As a source of mesenchymal cells, bone chips from GFP-Tg were injected intraperitoneally alone (MSC group) or along with i.v. bone marrow cells (BMT + MSC group). Controls were untreated mice (UnTx) or mice exposed to radiation only (Rad Cont). At 62 weeks post-transplant, surviving mice were harvested for histopathology, flow cytometry and real time polymerase chain reaction (RT-PCR). The mice from BMT + MSC group had the best outcomes for survival rates (71.4% vs. 43.8%), renal scores (2.9% vs. 28.8% glomerular sclerosis) and percent splenic monocytes (4.2 vs. 11.3%) compared with mice from Rad Cont. Improvement in RAG and BMT groups was less prominent but were comparable with one another. Although MSC alone were not sufficient to control the renal pathology, it limited the expansion of CD4−CD8− T cell populations without a change in Foxp3 expression. The results suggest the importance of the innate immune system in disease pathogenesis and a role for MSC in immunomodulation.
Time to neuropsychiatric damage occurrence in LUMINA (LXVI): a multi-ethnic lupus cohort
Authors: González LA , Pons-Estel GJ , Zhang J , Vilá LM , Reveille JD , Alarcón GS ,   for the LUMINA study group
Published: July 2009

The aims of this study were to examine the predictors of time to neuropsychiatric (NP) damage and its impact on mortality in 632 systemic lupus erythematosus African-American, Hispanic and Caucasian LUpus in MInorities: NAture versus Nurture (LUMINA) patients, age ≥ 16 years and disease duration ≤5 years at baseline (T0). Time-to-NP damage and its impact on mortality were examined by Cox proportional hazards regressions. A total of 185 (29.3%) patients developed NP damage over a mean (SD) disease duration of 5.6 (3.7) years. After adjusting for NP manifestations present, older age [Hazard ratio (HR) = 1.02; 95% Confidence interval (CI) 1.00–1.04], Caucasian ethnicity (HR = 1.87; 95% CI, 1.22–2.87), disease activity over the disease course (HR = 1.16; 95% CI, 1.12–1.21), diabetes (HR = 3.47; 95% CI, 1.44–8.38) and abnormal illness-related behaviours (HR = 1.05; 95% CI, 1.02–1.08) were associated with a shorter time-to-NP damage. Photosensitivity (HR = 0.65; 95% CI, 0.44–0.95), anaemia (HR = 0.56; 95% CI, 0.31–0.98), Raynaud’s phenomenon (HR = 0.49; 95% CI, 0.34–0.72), a medium dose of prednisone (HR = 0.56; 95% CI, 0.35–0.92) and hydroxychloroquine use (HR = 0.58; 95% CI, 0.36–0.93) were associated with a longer time. NP damage did not contribute to mortality. Older age, Caucasian ethnicity, disease activity and abnormal illness-related behaviours are associated with a shorter time-to-NP damage; hydroxychloroquine and a medium dose of prednisone with a longer time.
Dyspnoea in a young woman with active systemic lupus erythematosus
Authors: Todd DJ , Costenbader KH
Published: July 2009

Diffuse alveolar haemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). We present the case of a 24-year-old Cambodian woman with SLE followed in the Brigham and Women’s Hospital Lupus Center in Boston, Massachusetts. She presented with dyspnoea and chest pain and was found to have DAH that required a prolonged hospitalization that was complicated by recurrent DAH episodes and multiple infections. We discuss the diagnostic approach and management of patients with SLE-associated DAH as well as treatment options for refractory disease. Emerging therapies include plasmapheresis, the anti-CD20 monoclonal antibody rituximab and recombinant activated Factor VII therapy. In addition, we review the literature to date and compile what is known about the epidemiology, presenting features, diagnostic findings, management and outcomes in this condition. We found that DAH has been reported in 1.9% of patients with SLE. These patients were mostly female (88%) and young (mean age 30.2 years). Common presenting features included dyspnoea (94%), anaemia (97%) and new radiographic chest infiltrate (99%). Bronchoscopy, when performed, identified DAH in 90% of cases. Corticosteroids were the mainstay of care, and usage of cyclophosphamide varied by report. Despite recent advances in therapy, mortality has not improved substantially (48% overall survival versus 53% survival in reports published since 1993).
Rituximab in systemic lupus erythematosusA systematic review of off-label use in 188 cases
Authors: Ramos-Casals M , Soto MJ , Cuadrado MJ , Khamashta MA
Published: July 2009

The complexity of the therapeutic approach in systemic lupus erythematosus (SLE) is increased by the large number of patients who do not respond to the first-line therapies and by relapses after initial clinical remission. In these patients, second-line drugs are often prescribed according to individual clinical decisions. The emergence of biological therapies has increased the therapeutic armamentarium available in these complex situations, but their use is limited by the lack of licensing. Available data on the use of rituximab in SLE rely on a large number of case reports and some observational studies. We analyzed current evidence on the therapeutic use of rituximab in adult SLE patients by a systematic review of reports included in the PubMed database between 2002 and 2007. A total of 188 SLE patients treated with rituximab were identified; 171 (91%) patients showed a significant improvement in one or more of the systemic SLE manifestations. There were 103 patients with lupus nephritis, with an overall rate of therapeutic response of renal involvement of 91%. Adverse events were reported in 44 (23%) patients; the most frequent were infections (19%). Although it is not yet possible to make definite recommendations, the global analysis of all cases reported to date support the off-label use of rituximab in severe, refractory SLE cases, whereas its use as a first-line therapy or in patients with a predominantly mild form of the disease is not advised.
Raising Chicanos in the Great White North
Authors: Fordham-Hernández Traci
Published: July 2009

This article1 explores paradoxes in being the White mother of Mexican American children and discusses how some of its attendant issues contrast one another. The author, an American scholar, believes she is taught to think and to write, not from the heart, but from a detached and “objective,” cerebral cortex, and she sees the places, the prism through which the world is seen, are constantly shifting. The author writes of liminality and simultaneity, “I’m ‘swimming in the sea’ as both the swimmer, struggling, and part of the sea, itself, pulling myself under, drowning in between-ness . . .” The headings, “From the Shore,” provide a detached, theoretical reflection upon the author’s experiences as a White mother of mixed-race children: “I’m standing on the banks, looking into my experiences and speaking from my ’head’,” and the headings, “In the Sea,” provide stories: “I’m immersed in the depths of my experiences and reflecting from my ‘heart’.”
In the Dark: Young Men’s Stories of Sexual Initiation in the Absence of Relevant Sexual Health Information
Authors: Kubicek Katrina , Beyer William J. , Weiss George , Iverson Ellen , Kipke Michele D.
Published: July 2009

A growing body of research has investigated the effectiveness of abstinence-only sexual education. There remains a dearth of research on the relevant sexual health information available to young men who have sex with men (YMSM). Drawing on a mixed-methods study with 526 YMSM, this study explores how and where YMSM receive relevant information on sexual health/behavior. Findings indicate that information related to gay men’s sexuality is not readily available from family, friends, or schools. At initiation of anal intercourse, respondents generally had limited information about HIV and sexually transmitted infections (STIs). In some cases, this resulted in the perception that activities such as unprotected sex were “low risk.” Many mentioned they first learned about anal sex during their sexual debut, describing painful and/or unpleasant experiences. Some relied on older/more experienced partners, the Internet, and pornography for information. Findings are discussed in relation to how providers can help YMSM build solid foundations of sexual education to protect them from STI and HIV infection.
Environmental risk factors and health outcomes in selected communities of the Niger delta area, Nigeria
Authors: Ana Godson REE , Sridhar Mynepalli KC , Bamgboye Elijah A
Published: July 2009

Aims: The main aim of this study was to assess the prevalence of various health outcomes associated with exposure to environmental risk factors including industrial pollution in selected communities of Nigeria's oil-rich Niger delta area (NDA).

Methods: The study involved both laboratory experiments and community health surveys using questionnaires and hospital records. A total of 14 air samples, 16 grab soil samples and 18 surface water samples were collected and analyzed for physicochemical parameters including heavy metals and polycyclic aromatic hydrocarbons (PAHs) using standard methods. A 77-item questionnaire was administered on randomly selected 349 subjects. A five-year record was collected from health facilities located in the two communities.

Results: The laboratory results indicated that the median PAH level at Eleme as compared to Ahoada East was higher than the guideline limit 50 ng/l for surface waters. The mean TSP level at Eleme was higher than the level at Ahoada East and the guideline limit 100 µg/m3. The median PAH level at Eleme was higher than the level at Ahoada East and the guideline limit < 100 ng/m3 for air. The survey results showed that at Eleme air pollution in the community was significantly associated with painful body outgrowths ( p = 0.027) and the effect the air contaminants has was significantly associated with respiratory health problem ( p = 0.044). At Ahoada East commonly consumed aquatic food was highly significantly associated with painful body outgrowth ( p < 0.0001) while use of domestic cooking fuel types was also highly significantly associated with child deformities ( p < 0.0001). Hospital records showed high proportions of respiratory disorder among males (3.85%) and females (4.39%) at Eleme as compared to the proportion of respiratory disorder among males (3.68%) and females (4.18%) at Ahoada East.

Conclusions: The study shows that industrial communities such as Eleme, which are exposed to higher levels of air pollution, are more predisposed to respiratory morbidities, skin disorders and other related health risks.
The impact of well-developed preventative strategies on the eradication of head lice
Authors: Ibarra Joanna , Fry Frances , Wickenden Clarice , Jenner Maryan , Franks Andrea
Published: July 2009

In the 1970s Donaldson applied the principles of infectious disease surveillance to pediculosis capitis infestation with head lice. This provided a lasting insight into an effective strategy for prevention. Research in Teesside, UK, proved that the first step in breaking the chain of transmission is the engagement of parents in an intensive detection/treatment campaign. United action halved the infestation rate, even though failing lindane treatments were in use. Subsequently although effective malathion treatment was introduced, it became clear that the late detection of light cases of head lice still undermines eradication.

This paper analyzes the development by the health charity, Community Hygiene Concern, of the Bug Busting programme based on this solid evidence. In the 1990s the charity solved the problem of detecting asymptomatic lice using a specially designed Bug Buster louse comb in wet, conditioned hair. It undertook the popularization of this method and the co-ordination of national detection days (Bug Busting Days) through primary schools.

In 2004 this structured approach to prevention was adopted in Chester. It produced a 24% reduction in health authority spending on treatment products in the first year and appreciable savings in professional time.

It is concluded that participation in the Bug Busting programme benefits community health providers and schools. Provision of dependable detection combs with the correct instructions to families at risk, empowers them to gain sustainable, cost-effective control of head lice.
Sport, health and drugs: a critical re-examination of some key issues and problems
Authors: Vidar Hanstad Dag , Waddington Ivan
Published: July 2009

One of the major justifications for the ban on the use of performance-enhancing drugs in sport has been that relating to the protection of the health of athletes. This paper subjects this argument to critical analysis by putting it in the context of the broader relationship between sport and health. More particularly, the paper seeks to unravel some of the complexities of this relationship by an examination of: (i) some aspects of sports sponsorship, particularly with alcohol and tobacco companies; (ii) the health risks associated with elite level sport; and (iii) the widespread and legal use within the sporting context of drugs that can have dangerous side effects. The paper concludes with an examination of some aspects of anti-doping policies within sport and it is suggested that a more imaginative approach to athlete education is needed to prevent the misuse of drugs.
Crowdsourcing the Public Participation Process for Planning Projects
Authors: Brabham Daren C.
Published: July 2009

Public involvement is a central concern for urban planners, but the challenge for planners is how best to implement such programs, given many difficulties inherent in the typical public involvement process. The medium of the Web enables us to harness collective intellect among a population in ways face-to-face planning meetings cannot. This article argues that the crowdsourcing model, a successful, Web-based, distributed problem solving and production model for business, is an appropriate model for enabling the citizen participation process in public planning projects. This article begins with an exploration of the challenges of public participation in urban planning projects, particularly in the harnessing of creative solutions. An explanation of the theories of collective intelligence and crowd wisdom follows, arguing for the medium of the Web as an appropriate technology for harnessing far-flung genius. An exploration of crowdsourcing in a hypothetical neighborhood planning example, along with a consideration of the challenges of implementing crowdsourcing, concludes the article.
Democratic Anchorage of Infrastructural Governance Networks: the Case of the Femern Belt Forum
Authors: Torfing Jacob , Sørensen Eva , Fotel Trine
Published: July 2009

Governance networks are often praised for their contribution to making public governance and spatial planning more effective. However, the democratic performance of governance networks is heavily disputed. In order to make a more precise assessment of the democratic quality of governance networks, we need to develop normative criteria that permit us to measure the democratic quality of governance networks on different dimensions. Such criteria are developed and brought together in our model for the democratic anchorage of governance networks. This article aims to improve the democratic anchorage model in two different ways: by offering operational definitions of the basic dimensions of the model and by demonstrating how the assessment criteria can be applied in an empirical case study of a long-lasting, multilevel governance network involved in the recent decision to build a bridge between Denmark and Germany. The democratic anchorage model helps to assess the democratic performance of specific governance networks and to gain knowledge about the critical factors determining their degree of democratic anchorage. Such knowledge is crucial for developing pro-active strategies for enhancing the democratic performance of specific governance networks.
Planning Craft: How Planners Compose Plans
Authors: Hoch Charles
Published: July 2009

Conceiving urban plan making as practical judgment shifts theoretical attention from questions of belief to questions of meaning. How do we make urban plans that combine intelligent coordination with savvy communication to anticipate and cope with urban complexity? Consider adopting a pragmatic approach that relies on coherence to inform the appraisal, comparison and selection that accompany practical judgment. Plans compose the meaning and consequence of future actions. Pragmatic composition combines representation and interpretation to frame problems of urban complexity. Four orientations are described using plan examples: protocol, precedent, prototype and policy.
Glycaemic control and restenosis after percutaneous coronary interventions in patients with diabetes mellitus: a report from the Insulin Diabetes Angioplasty study
Authors: Hage Camilla , Norhammar Anna , Grip Lars , Malmberg Klas , Sarkar Nondita , Svane Bertil , Rydén Lars
Published: July 2009

Objective: We investigated the impact of glucose control on target lesion restenosis after PCI in patients with type 2 diabetes.

Methods: Ninety-three consecutive patients with type 2 diabetes accepted for PCI were randomised to intensified glucose control based on insulin (I-group; n=44) or to continue ongoing glucose-lowering treatment (C-group; n=49).The treatment target was a FBG of 5—7 mmol/L and HbA1c <6.5%. Information on target lesion restenosis after six months was available in 82 patients.

Results: At baseline HbA1c and FBG did not differ between the I- and C-groups, respectively (HbA1c: 6.5 vs. 6.5%; p=1.0 and FBG: 7.0 vs. 7.3 mmol/L; p=0.3). After six months there was no significant change in HbA1c or FBG in either group (change in HbA1c: -0.2 vs.-0.1%; p=0.3 and in FBG: +0.2 vs. -0.3 mmol/L; p=0.3 in the I- and C-groups, respectively). Target lesion restenosis at six months did not differ, I vs. C = 41 and 44% (p=0.8). Independent predictors for restenosis were previous myocardial infarction (OR 8.0, 95% CI 2.5—25.7; p=<0.001) and FBG at baseline (OR for an increase by 1 mmol/L = 1.4, 95% CI 1.1—1.9; p=0.015).

Conclusions: Restenosis was predicted by baseline FBG suggesting that it would be of interest to target glucose normalisation in future trials. Intensified insulin treatment did not influence the rate of restenosis indicating that the main focus should be on lowering glucose rather than the tool to normalise glucose.
Prevalence and risk factors for peripheral artery disease in an Asian population with diabetes mellitus
Authors: Tavintharan S. , Ning Cheung  , Su Chi Lim  , Tay Wanting , Shankar Anoop , Shyong Tai E. , Wong Tien Y.
Published: July 2009

We describe the prevalence and risk factors for PAD in Asian Malays with diabetes. A population-based study of 3,280 (78.7% response) Malay persons aged 40—80 years in Singapore was conducted. ABI was measured in all participants with a history of diabetes (N=634). PAD was defined to be present if ABI ≤ 0.9. All participants had standardised interviews, clinical examinations and laboratory investigation for risk factor assessment. The crude prevalence of PAD was 10.4% (95% CI: 8.3%—13.0%). After age standardisation to the 2000 Singapore Census population, the prevalence was 5% (95% CI: 3.8—8.6). In multivariate analyses, the presence of PAD was associated with older age (OR 1.05; 95% CI: 1.01—1.09, per year increase), female gender (OR 4.18; 95% CI: 1.67—10.43), cigarette smoking (OR 2.55; 95% CI: 1.05—6.20), higher systolic blood pressure (OR 1.28; 95% CI: 1.13—1.45), a history of myocardial infarction (OR 3.69; 95% CI: 1.79—7.61) and stroke (OR 3.06 95% CI: 1.25—7.50). In this Asian Malay population with diabetes, we found a high prevalence of PAD.The major risk factors for PAD among persons with diabetes are similar to studies in Caucasian populations, suggesting that strategies aimed at controlling the modifiable factors may reduce the prevalence of PAD in Asian populations.
Apo-B/AI ratio identifies cardiovascular risk in childhood:The Australian Aboriginal Birth Cohort study
Authors: Sellers Elizabeth A.C. , Singh Gurmeet R. , Sayers Susan M.
Published: July 2009

We describe the lipoprotein and apolipoprotein profiles and their relationship to cardiovascular risk factors in Australian Aboriginal children. This cross-sectional study within a longitudinal birth cohort study involved Australian Aboriginal children born between 1987 and 1990 and re-examined between 1998 and 2001. Height, weight, blood pressure, waist circumference, body fat percentage, cholesterol, triglycerides, HDL-c, LDL-c, apolipoprotein B and A1 were measured. Mean age was 11.4 years (52% male). Mean cholesterol, triglyceride, HDL-c and LDL-c did not differ from reference data. Measures of obesity, blood pressure and prevalence of the metabolic syndrome did not differ in those children with lipoproteins in the upper quartile of the cohort (lower quartile for HDL-c). Boys with an Apo-B/A1 ratio in the upper quartile of the cohort had higher BMI z-score, waist z-score, % body fat, diastolic blood pressure and frequency of the metabolic syndrome (p<0.05). In girls, waist circumference, % body fat and the prevalence of the metabolic syndrome was higher in those with an Apo-B/A1 ratio in the upper quartile (p<0.05).The Apo-B/A1 ratio may be useful to identify cardiovascular risk in Australian Aboriginal children and is suited to clinical practice as the assays are standardised, accurate, automated and a fasting sample is not required.
Stroke and cardiovascular morbidity and mortality associated with rosiglitazone use in elderly diabetic patients
Authors: Vanasse Alain , Carpentier André C. , Courteau Josiane , Asghari Shabnam
Published: July 2009

The objective was to evaluate the cardiovascular risks associated with rosiglitazone in diabetic patients. We conducted matched nested case—control studies in a retrospective population-based cohort of all elderly diabetic patients living in Quebec throughout 2001 and 2002. Study end-points were: all-cause and cardiovascular death, hospital admission for AMI, CHF and stroke.Twenty controls per case, matched for age, gender and date of cohort entry, were randomly drawn from each case's risk set. Conditional logistic regressions were adjusted for co-morbidities and other drug exposures. The risk of hospital admission for AMI (HR 1.41, 95% CI 1.21—1.65) and CHF (HR 1.94, 95% CI 1.71—2.19) was increased by the use of rosiglitazone. However, exposure to rosiglitazone was not associated with an increased risk of cardiovascular mortality (HR 0.88, 95% CI 0.69—1.12) and all-causes mortality (HR 0.87, 95% CI 0.76—0.99).The risk of hospital admission for stroke was not significantly affected by rosiglitazone use. Further studies are needed to better understand the mechanisms explaining these associations.
Coadministration of muraglitazar plus glyburide: Improvement of glycaemic and lipid profiles in patients with type 2 diabetes
Authors: Rubin Cindy J. , De Pril Veerle , Fiedorek Fred T.
Published: July 2009

In this trial we evaluated the efficacy and safety of muraglitazar, a dual (α/γ) peroxisome proliferator-activated receptor activator, plus glyburide in patients with type 2 diabetes not controlled with sulphonylurea monotherapy. After 2 weeks of open-label glyburide (15 mg/day), 583 patients were randomised to additionally receive muraglitazar 2.5 mg, 5 mg, or placebo. End points included changes in HbA1C and fasting plasma glucose (FPG) at weeks 24 and 102, and changes in lipid parameters at weeks 11/12 and 102.At week 24, mean changes from baseline in HbA1C and FPG were significantly greater with glyburide plus muraglitazar 2.5 mg or 5 mg than with glyburide plus placebo (p<0.0001). At week 11/12, triglyceride levels were significantly reduced with muraglitazar (p<0.0001). During the extension phase, muraglitazar demonstrated long-term glycaemic and lipid effects through week 102. Although generally well tolerated, muraglitazar was associated with higher rates of congestive heart failure, cardiovascular events, weight gain and oedema.
Long-term effect of metformin on metabolic parameters in the polycystic ovary syndrome
Authors: Cheang Kai I. , Huszar Jessica M. , Best Al M. , Sharma Susmeeta , Essah Paulina A. , Nestler John E.
Published: July 2009

Insulin resistance is a central feature of the PCOS and may increase cardiovascular risk. Owing to insulin resistance, the metabolic syndrome is more prevalent in women with PCOS compared with unaffected women. Metformin improves the metabolic profile in PCOS in short-term studies. In this study, we evaluated the long-term effect of metformin on metabolic parameters in women with PCOS during routine care without a controlled diet.We performed a retrospective medical chart review of 70 women with PCOS receiving metformin from an academic endocrine clinic. Metabolic risk factors were compared before and after metformin treatment. Time trends of these metabolic parameters were also analysed. After a mean follow-up of 36.1 months with metformin treatment, improvements were observed for BMI (—1.09 ± 3.48 kg/m2, p = 0.0117), diastolic blood pressure (—2.69 ± 10.35 mmHg, p = 0.0378), and HDL cholesterol (+5.82 ± 11.02 mg/dL, p <0.0001).The prevalence of metabolic syndrome decreased from 34.3% at baseline to 21.4% (p = 0.0495). The course of BMI reduction during metformin treatment was significantly more pronounced in women with PCOS with metabolic syndrome at baseline, compared with those without the metabolic syndrome (p = 0.0369 for interaction). In conclusion, metformin improved the metabolic profile of women with PCOS over 36.1 months, particularly in HDL cholesterol, diastolic blood pressure and BMI.
A gluco-metabolic risk index with cardiovascular risk stratification potential in patients with coronary artery disease
Authors: Anselmino Matteo , Malmberg Klas , Rydén Lars , Öhrvik John
Published: July 2009

The primary objective of this study was to classify patients with CAD as regards their gluco-metabolic state by easily available clinical variables. A secondary objective was to explore if it was possible to identify CAD patients at a high cardiovascular risk due to metabolic perturbations. The 1,867 patients with CAD were gluco-metabolically classified by an OGTT. Among these, 990 patients had complete data regarding all components of the metabolic syndrome, BMI, HbA1c and medical history. Only FPG and HDL-c adjusting for age significantly impacted OGTT classification. Based on these variables, a neural network reached a cross-validated misclassification rate of 37.8% compared with OGTT. By this criterion, 1,283 patients with complete one-year follow-up concerning all-cause mortality, myocardial infarction and stroke (CVE) were divided into low- and high-risk groups within which CVE were, respectively, 5.1 and 9.4% (p=0.016).Adjusting for confounding variables the relative risk for a CVE based on the neural network was 2.06 (95% CI: 1.18—3.58) compared with 1.37 (95% CI: 0.79—2.36) for OGTT. Conclusions:The neural network, based on FPG, HDL-c and age, showed useful risk stratification capacities; it may, therefore, be of help when stratifying further risk of CVE in CAD patients.
Subjective Fatigue, Mental Effort, and Attention Deficits After Severe Traumatic Brain Injury
Authors: Belmont Angelique , Agar Nathalie , Azouvi Philippe
Published: July 2009

Objective. Although fatigue is one of the most frequent complaints of individuals with traumatic brain injury (TBI), its mechanisms remain poorly understood. The objective of this study was to assess the relationships between subjective mental fatigue, mental effort, attention deficits, and mood after severe TBI. Methods and participants. A total of 27 patients with subacute/chronic severe TBI were compared with matched controls. Patients first rated their baseline subjective fatigue on the Fatigue Severity Scale (FSS) and on the Visual Analog Scale for Fatigue (VAS-F). Mood was assessed with the Montgomery and Asberg Depression Rating Scale (MADRS). Then, they performed a long-duration selective attention task, separated in 2 parts. Fatigue on the VAS-F was assessed again between the 2 parts and at the end of the attention task. Patients were also asked to rate on the VAS the level of subjective mental effort devoted to the task. Results. Patients reported a higher baseline fatigue than controls. They performed significantly poorer on the selective attention task. Significant correlations were found in the group with TBI between attention performance, mental effort, and subjective fatigue. Depression did not significantly correlate with fatigue. Discussion and conclusions. These findings suggest that patients with more severe attention deficits have to produce higher levels of mental effort to manage a complex task, which may increase subjective fatigue, in line with the coping hypothesis.
Some mechanical aspects of arterial aging: physiological overview based on pulse wave analysis
Authors: Hashimoto Junichiro , Ito Sadayoshi
Published: July 2009

Aging has a striking impact on the arterial structure and function. The principal structural change with age is medial degeneration that leads to a progressive stiffening of the large elastic arteries. Large artery stiffening increases aortic systolic and pulse pressures through an increase in the forward incident wave and an early return of the backward reflected wave. Peripheral muscular arteries/arterioles are only minimally affected in structure by aging itself, but impaired vasomotor function can alter their impedance properties and thereby increase reflection magnitude. An augmented aortic pressure due to enhanced wave reflection increases wasted left ventricular effort and causes cardiac hypertrophy. Increased pulsatile pressure and flow stresses extend to the vulnerable microcirculation of vasodilated organs such as the brain and kidneys, and can predispose to cerebral lacunar infarction and albuminuria. Although most currently available vasodilators appear to have little direct effect on degenerated elastic arteries, they can act instead on less-degenerated muscular arteries to markedly reduce peripheral wave reflection magnitude and central aortic pressure, and thus contribute to the regression of left ventricular hypertrophy. Further studies are necessary to examine whether the effect of vasodilator therapy on reducing wave reflection contributes similarly to the prevention of microvascular damage in the brain and kidneys.
“Self”-reflection by KIR
Authors: Cooley Sarah , Miller Jeffrey S.
Published: July 2009

Significant debate exists over the proposed mechanisms by which NK receptor expression coordinates with the acquisition of function and titration of responsiveness, a process called NK-cell education. In this issue of Blood, Andersson and colleagues provide new insights into the mechanisms underlying NK-cell repertoire formation and the modulation of NK-cell function.1
Transcutaneous carbon dioxide profile during sleep reveals metabolic risk factors in post-menopausal females
Authors: Aittokallio J. , Saaresranta T. , Virkki A. , Karppinen N. , Heinonen O. J. , Aittokallio T. , Polo O.
Published: July 2009

The risks of metabolic syndrome and sleep-disordered breathing increase around the time of the menopause. We have previously shown that features of the nocturnal transcutaneous carbon dioxide (TcCO2) profile are associated with metabolic variables such as cholesterol, glycosylated haemoglobin A1C (GHbA1C) and blood pressure in patients with sleep apnoea. In the present study, we investigated whether these metabolic variables can be predicted using noninvasive TcCO2measurements during sleep in generally healthy post-menopausal females.

22 post-menopausal females underwent an overnight polygraphic sleep study that involved the continuous monitoring of arterial oxygen saturation (Sa,O2) and TcCO2. Body composition, GHbA1C, plasma cholesterol and blood pressure were measured prior to the sleep study.

Nocturnal TcCO2features were the most important predictors of lipoprotein cholesterols, triglycerides and blood pressure levels. A longer sleep period and higher TcCO2levels were linked with lower GHbA1C, and fragmented sleep with lower high-density lipoprotein cholesterol. Neither nocturnalSa,O2indices nor the apnoea/hypopnoea index had a predictive power.

The results suggest that nocturnal TcCO2events revealed metabolic risk factors already present in healthy post-menopausal females.
Airflow obstruction and metabolic syndrome: the Guangzhou Biobank Cohort Study
Authors: Lam K-B. H. , Jordan R. E. , Jiang C. Q. , Thomas G. N. , Miller M. R. , Zhang W. S. , Lam T. H. , Cheng K. K. , Adab P.
Published: July 2009

There is some evidence that chronic obstructive pulmonary disease (COPD) and metabolic syndrome may be related, perhaps through systemic inflammation, which is common to both. However, the association between the two conditions has not yet been clearly shown.

The present study involved 7,358 adults aged ≥50 yrs from a population-based survey who underwent spirometry, a structured interview and measurement of fasting metabolic marker levels.

Airflow obstruction (forced expiratory volume in 1 s/forced vital capacity ratio of less than the lower limit of normal) was present in 6.7%, and the International Diabetes Federation metabolic syndrome criteria were met by 20.0%. The risk of metabolic syndrome was higher in those with airflow obstruction than in those without (odds ratio (OR) 1.47; 95% confidence interval (CI) 1.12–1.92), after controlling for potential confounders. Of the five components of metabolic syndrome, only central obesity was significantly associated with airflow obstruction (OR 1.43; 95% CI 1.09–1.88) after adjusting for body mass index. A similar association was observed in both never and current smokers.

In this Chinese sample, airflow obstruction was associated with metabolic syndrome, and, in particular, its central obesity component. This may help explain the increased risk of cardiovascular diseases in COPD, and so could guide future clinical practice.
Is INTERdisciplinary COMmunity-based COPD management (INTERCOM) cost-effective?
Authors: Hoogendoorn M. , van Wetering C. R. , Schols A. M. , Rutten-van Mölken M. P. M. H.
Published: July 2009

The study aimed to estimate the cost-effectiveness of interdisciplinary community-based chronic obstructive pulmonary disease (COPD) management in patients with COPD.

We conducted a cost-effectiveness analysis alongside a 2-yr randomised controlled trial, in which 199 patients with less advanced airflow obstruction and impaired exercise capacity were assigned to the INTERCOM programme or usual care. The INTERCOM programme consisted of exercise training, education, nutritional therapy and smoking cessation counselling offered by community-based physiotherapists and dieticians and hospital-based respiratory nurses. All-cause resource use during 2 yrs was obtained by self-report and from hospital and pharmacy records. Health outcomes were the St George's Respiratory Questionnaire (SGRQ), exacerbations and quality-adjusted life years (QALYs).

The INTERCOM group had 30% (95% CI 3–56%) more patients with a clinically relevant improvement in SGRQ total score, 0.08 (95% CI -0.01–0.18) more QALYs per patient, but a higher mean number of exacerbations, 0.84 (95% CI -0.07–1.78). Mean total 2-yr costs were €2,751 (95% CI -€632–€6,372) higher for INTERCOM than for usual care, which resulted in an incremental cost-effectiveness ratio of €9,078 per additional patient with a relevant improvement in SGRQ or €32,425 per QALY.

INTERCOM significantly improved disease-specific quality of life, but did not affect exacerbation rate. The cost per QALY ratio was moderate, but within the range of that generally considered to be acceptable.
Long-term time-course of nocturnal breathing disorders in heart failure patients
Authors: Pinna G. D. , Maestri R. , Mortara A. , Johnson P. , Andrews D. , Ponikowski P. , Witkowski T. , La Rovere M. T. , Sleight P.
Published: July 2009

Some important aspects of clinical manifestations of nocturnal breathing disorders in heart failure (HF) patients are still unknown. We questioned whether the severity of these disorders, first, is stable over time; secondly, shows any systematic trend; and, thirdly, can be predicted over time by a single baseline measurement.

We studied 79 stable, optimally treated, moderate-to-severe HF patients who performed a monthly cardiorespiratory recording during 1-yr follow-up. According to their behaviour over time, nocturnal breathing disorders were classified as persistent, absent or occasional.

During follow-up, clinically relevant breathing disorders were persistent in ∼50% of the patients, absent in <20% and occasional in ∼30%. Increasing/decreasing trends were rarely observed. The positive and negative predictive value of baseline measurement for persistent behaviour over time ranged, respectively, from 71% to 91% and from 91% to 95%, depending on different levels of severity of breathing disorders.

A large portion of HF patients experience persistent clinically significant nocturnal breathing disorders over long periods of time. Breathing disorders occur irregularly in about one-third of the patients and are negligible in a minority of them. Rarely do they show a steady increase or decrease over time. A single baseline recording predicts a persistent behaviour with moderate-to-high accuracy.
Interleukin-8 activates coagulation and correlates with survival after talc pleurodesis
Authors: Montes-Worboys A. , Rodriguez-Portal J. A. , Arellano-Orden E. , Digón-Pereiras J. , Rodriguez-Panadero F.
Published: July 2009

The aim of our study was to investigate whether interleukin (IL)-8 activates systemic coagulation after talc pleurodesis in malignant pleural effusion (MPE), and whether levels of IL-8 in plasma are related to early death after talc pleurodesis.

IL-8 and tumour necrosis factor (TNF)-α were measured in samples from 231 MPE patients before and after talc pleurodesis. Whole blood from 31 healthy volunteers was incubated with IL-8, TNF-α and thromboplastin for 3 hin vitro, and thrombin-antithrombin (TAT) levels were measured. The same stimulation of blood samples was repeated using doses of calibrated talc.

Nine, 12 and 17 patients died within 7, 10 and 15 days respectively. IL-8 was elevated in 102 patients within 48 h, and thrombotic events were observed in six of those patients. Survival correlated inversely with IL-8 at 24 and 48 h, and a significant correlation was also found between IL-8 and TAT. A positive dose–dependent correlation with TAT production was observed when blood was stimulated with IL-8in vitro. However, there was no significant response to stimulation with talc, as compared with control blood samples.

IL-8 is involved in the activation of coagulation that may occur after talc pleurodesis, and might also be implicated in early death of patients with MPE.
Quality of randomised trials in COPD
Authors: Bausch B. , Spaar A. , Kleijnen J. , Puhan M. A.
Published: July 2009

Randomised trials can provide high-level evidence to inform treatment decisions. Since their quality in respiratory medicine is largely unknown, we assessed the quality of a large set of chronic obstructive pulmonary disease (COPD) trials.

As a marker of trial quality, we assessed the procedure and concealment of random allocation, and the conduct of an intention-to-treat-analysis in 344 randomised trials published between 1957 and 2006. We used ordered logistic regression to assess the association between trial quality and type of intervention, type of journal, journal impact factor and year of publication.

257 (75%) trials assessed pharmacological and 87 (25%) assessed nonpharmacological interventions. The generation of appropriate randomisation was reported in 27.0% of the trials, concealment of random allocation in 11.6% and an intention-to-treat analysis in 21.8% of trials. Significantly higher quality was found in trials on nonpharmacological interventions (OR 2.49, 95% CI 1.56–3.99), and in trials published in general medical journals (versusspecialised journals; OR 2.25, 95% CI 1.30–3.90) and after 2000 (versus1957–2000; OR 2.28, 95% CI 1.45–3.58). The association of quality with a high impact factor was of borderline significance (p = 0.06).

The quality of many COPD trials is low but tends to become better since the adoption of the CONSORT (Consolidated Standards of Reporting Trials) statement.
Bronchial nitric oxide is related to symptom relief during fluticasone treatment in COPD
Authors: Lehtimäki L. , Kankaanranta H. , Saarelainen S. , Annila I. , Aine T. , Nieminen R. , Moilanen E.
Published: July 2009

High levels of exhaled nitric oxide (NO) predict favourable response to inhaled corticosteroids in asthma, but the ability of exhaled NO or inflammatory markers in exhaled breath condensate (EBC) to predict steroid responsiveness in chronic obstructive pulmonary disease (COPD) is not known.

We measured alveolar and bronchial NO output, levels of leukotriene B4(LTB4), cysteinyl leukotrienes (cysLTs) and 8-isoprostane in EBC, spirometry, body plethysmography and symptoms in 40 subjects with COPD before and after 4 weeks of treatment with inhaled fluticasone (500 μgb.i.d.).

Five subjects (12.5%) with COPD had significant improvement in lung function during fluticasone treatment, whereas 20 subjects (50%) had significant decrease in symptoms. High baseline bronchial NO flux was associated with higher increase in forced expiratory volume in 1 s to forced vital capacity ratio (r = 0.334, p = 0.038) and more symptom relief (r =  -0.317, p = 0.049) during the treatment. Baseline EBC levels of LTB4, cysLTs or 8-isoprostane were not related to response to fluticasone treatment. Inhaled fluticasone decreased bronchial NO flux but not alveolar NO concentration or markers in EBC.

High levels of bronchial NO flux are related to symptom relief and improvement of airway obstruction during treatment with inhaled fluticasone in COPD. Markers of inflammation or oxidative stress in EBC are not related to steroid responsiveness in COPD.