Infection rates in patients from five rheumatoid arthritis (RA) registries: contextualising an RA clinical trial programme.

Objective: Patients with rheumatoid arthritis (RA) have an increased risk of serious infections. Comparing infection rates across RA populations is complicated by differences in background infection risk, population composition and study methodology. We measured infection rates from five RA registries globally, with the aim to contextualise infection rates from an RA clinical trials population.

Association of faecal elastase 1 with non-fasting triglycerides in type 2 diabetes.

Aims: Intestinal absorption of esterified fatty acids depends on exocrine pancreatic function and influences plasma triglycerides levels. The aim was to investigate the association of reduced exocrine pancreatic function (low fecal elastase-1; FE1) with plasma triglycerides in type 2 diabetes and controls without diabetes.

Methods: FE1 (μg/g stool) and non-fasting plasma triglyceride measurements were undertaken in 544 type 2 diabetes patients (age: 63 ± 8 years) randomly selected from diabetes registers in Cambridgeshire (UK), and 544 matched controls (age, sex, practice) without diabetes.

Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease.

Background: We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality.

Methods: Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions.

How comparable are rates of malignancies in patients with rheumatoid arthritis across the world? A comparison of cancer rates, and means to optimise their comparability, in five RA registries.

Background: The overall incidence of cancer in patients with rheumatoid arthritis (RA) is modestly elevated. The extent to which cancer rates in RA vary across clinical cohorts and patient subsets, as defined by disease activity or treatment is less known but critical for understanding the safety of existing and new antirheumatic therapies. We investigated comparability of, and means to harmonise, malignancy rates in five RA registries from four continents.

Inverse association of HbA1c with faecal elastase 1 in people without diabetes.

Background/objectives: Faecal elastase 1 (FE1) was inversely correlated with diabetes duration and HbA1c in type 2 diabetes. The association of FE1 and HbA1c has not been investigated in people without diabetes.

Methods: Type 2 diabetes patients (oral antidiabetic drugs or insulin: n = 391; medically untreated: n = 145) and matched (age, sex, practice) people without diabetes (n = 529) from general practices in Cambridgeshire (UK) were included.

Using epidemiological registry data to provide background rates as context for adverse events in a rheumatoid arthritis drug development program: a coordinated approach.

Purpose: Observational studies can provide context for adverse events observed in clinical trials, especially for infrequent events or long-term risks. We developed methods to improve safety contextualization for a rheumatoid arthritis drug development program through coordinated analyses of multiple registries.

Methods: We identified and characterized differences and similarities across five registries (Swedish Rheumatology Quality of Care Register, Consortium of Rheumatology Researchers of North America [CORRONA], Norfolk Arthritis Register, Institute of Rheumatology Rheumatoid Arthritis, and the new CORRONA International), harmonized outcome definitions, and investigated whether restricted subcohorts improved comparability with trial populations.

Methodological Challenges When Comparing Demographic and Clinical Characteristics of International Observational Registries.

Objective: Comparisons of data from different registries can be helpful in understanding variations in many aspects of rheumatoid arthritis (RA). The study aim was to assess and improve the comparability of demographic, clinical, and comorbidity data from 5 international RA registries.

Methods: Using predefined definitions, 2 subsets of patients (main cohort and subcohort) from 5 international observational registries (Consortium of Rheumatology Researchers of North America Registry [CORRONA], the Swedish Rheumatology Quality of Care Register [SRR], the Norfolk Arthritis Register [NOAR], the Institute of Rheumatology Rheumatoid Arthritis cohort [IORRA], and CORRONA International) were evaluated and compared.

Long-term 4-year safety of saxagliptin in drug-naive and metformin-treated patients with Type 2 diabetes.

Aims: To evaluate the safety of saxagliptin ± metformin over 4 years in patients with Type 2 diabetes mellitus.

Methods: Drug-naive (n = 401; study 11) or metformin-treated (n = 743; study 14) adults with HbA(1c) of 53-86 mmol/mol (7.0-10%) were enrolled in two randomized, placebo-controlled, double-blind trials of saxagliptin 2.

The efficacy and safety of the dipeptidyl peptidase-4 inhibitor saxagliptin in treatment-naïve patients with type 2 diabetes mellitus: a randomized controlled trial.

Background: The aim of this study was to assess efficacy and safety of saxagliptin monotherapy for up to 76 weeks in patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control, with main efficacy assessment at 24 weeks.

Methods: 365 treatment-naïve patients with T2DM (HbA1c 7.0%-10.

Saxagliptin and metformin XR combination therapy provides glycemic control over 24 hours in patients with T2DM inadequately controlled with metformin.

Objective: To assess 24-hour glycemic control with saxagliptin compared with placebo as add-on treatment to metformin in patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control.

Research Design And Methods: This was a 4-week, multicenter, randomized, double-blind, placebo-controlled Phase IIIb trial comparing the antihyperglycemic activity of saxagliptin 5 mg once daily in combination with a stable dose of metformin extended release (XR) vs. placebo in combination with metformin XR in patients with T2DM inadequately controlled (screening glycated hemoglobin [HbA(1c)] 7-10%) with stable doses of metformin immediate release or metformin XR ≥ 1500 mg/day.

Air pollution exposure--a trigger for myocardial infarction?

The association between ambient air pollution exposure and hospitalization for cardiovascular events has been reported in several studies with conflicting results. A case-crossover design was used to investigate the effects of air pollution in 660 first-time myocardial infarction cases in Stockholm in 1993-1994, interviewed shortly after diagnosis using a standard protocol. Air pollution data came from central urban background monitors.

A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for type 2 diabetes.

Objective: The objective was to assess the relative risk (RR) for cardiovascular (CV) events across all 8 randomized phase 2/3 trials evaluating saxagliptin in patients with type 2 diabetes mellitus.

Methods: Cardiovascular events (death, myocardial infarction [MI], stroke, revascularization procedures, and cardiac ischemia) were reported by investigators through standard adverse event reporting procedures and were systematically identified. Post hoc blinded adjudication of all deaths, MIs, and strokes was performed using prespecified endpoint definitions by an independent clinical events committee (CEC).

Clival chordomas: clinical management, results, and complications in 71 patients.

Object: Chordomas are rare malignant neoplasms arising predominantly at the sacrum and skull base. They are uniformly lethal unless treated with aggressive resection and proton beam irradiation. The authors present results of the surgical management of a large number of patients with clivus chordomas.

Rapid effects of air pollution on ventricular arrhythmias.

Aims: Air pollution has been associated with ventricular arrhythmias in patients with implantable cardioverter defibrillators (ICDs) for exposure periods of 24-48 h. Only two studies have investigated exposure periods <24 h. We aimed to explore such effects during the 2 and 24 preceding hours as well as in relation to distance from the place of the event to the air pollution monitor.

Ambient air pollution and daily mortality among survivors of myocardial infarction.

Background: Certain subgroups in the general population, such as persons with existing cardiovascular or respiratory disease, may be more likely to experience adverse health effects from air pollution.

Methods: In this European multicenter study, 25,006 myocardial infarction (MI) survivors in 5 cities were recruited from 1992 to 2002 via registers, and daily mortality was followed for 6 to 12 years in relation to ambient particulate and gaseous air pollution exposure. Daily air pollution levels were obtained from central monitor sites, and particle number concentrations were measured in 2001 and estimated retrospectively based on measured pollutants and meteorology.

Interactions between glutathione S-transferase P1, tumor necrosis factor, and traffic-related air pollution for development of childhood allergic disease.

Background: Air pollutants may induce airway inflammation and sensitization due to generation of reactive oxygen species. The genetic background to these mechanisms could be important effect modifiers.

Objective: Our goal was to assess interactions between exposure to air pollution and single nucleotide polymorphisms (SNPs) in the beta2-adrenergic receptor (ADRB2), glutathione S-transferase P1 (GSTP1), and tumor necrosis factor (TNF) genes for development of childhood allergic disease.

Traffic-related air pollution and childhood respiratory symptoms, function and allergies.

Background: Urban air pollution can trigger asthma symptoms in children, but there is conflicting evidence on effects of long-term exposure on lung function, onset of airway disease and allergic sensitization.

Methods: The spatial distribution of nitrogen oxides from traffic (traffic-NOx) and inhalable particulate matter from traffic (traffic-PM10) in the study area was assessed with emission databases and dispersion modeling. Estimated levels were used to assign first-year exposure levels for children in a prospective birth cohort (n = 4089), by linking to geocoded home addresses.

Air pollution and inflammation (interleukin-6, C-reactive protein, fibrinogen) in myocardial infarction survivors.

Background: Numerous studies have found that ambient air pollution has been associated with cardiovascular disease exacerbation.

Objectives: Given previous findings, we hypothesized that particulate air pollution might induce systemic inflammation in myocardial infarction (MI) survivors, contributing to an increased vulnerability to elevated concentrations of ambient particles.

Methods: A prospective longitudinal study of 1,003 MI survivors was performed in six European cities between May 2003 and July 2004.

Road traffic noise and hypertension.

Background: It has been suggested that noise exposure increases the risk of hypertension. Road traffic is the dominant source of community noise exposure.

Objective: To study the association between exposure to residential road traffic noise and hypertension in an urban municipality.

Aldosterone-to-renin ratio as a marker for disease severity in 21-hydroxylase deficiency congenital adrenal hyperplasia.

Context: Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21 OHD) is classified clinically in decreasing order of severity into salt-wasting, simple-virilizing, and nonclassical forms. Causative mutations in the CYP21A2 gene dictate the degrees of adrenal enzyme defect. Salt-wasting crises due to aldosterone deficiency are clinically apparent in the salt-wasting form but not in other forms of 21 OHD.

Associations of traffic related air pollutants with hospitalisation for first acute myocardial infarction: the HEAPSS study.

Background: Acute myocardial infarction (AMI) is the leading cause of death attributed to cardiovascular diseases. An association between traffic related air pollution and AMI has been suggested, but the evidence is still limited.

Objectives: To evaluate in a multicentre study association between hospitalisation for first AMI and daily levels of traffic related air pollution.

Comparison of different methods in analyzing short-term air pollution effects in a cohort study of susceptible individuals.

Background: Short-term fluctuations of ambient air pollution have been associated with exacerbation of cardiovascular disease. A multi-city study was designed to assess the probability of recurrent hospitalization in a cohort of incident myocardial infarction survivors in five European cities. The objective of this paper is to discuss the methods for analyzing short-term health effects in a cohort study based on a case-series.

Long-term exposure to urban air pollution and myocardial infarction.

Background: Cohort studies have reported increased risks of cardiopulmonary mortality from long-term air pollution exposure, but the evidence is limited and inconclusive. We studied the association between long-term exposure to source-specific air pollution and myocardial infarction (MI) in a case-control study of first-time MI cases and population controls age 45 to 70 years in Stockholm county in 1992 to 1994.

Methods: Home addresses during several decades were combined with historical emission databases and dispersion models to obtain annual mean levels of pollutants from traffic and heating during 30 years for 1397 cases and 1870 controls.

Ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in five European cities.

Background: Ambient air pollution has been associated with increases in acute morbidity and mortality. The objective of this study was to evaluate the short-term effects of urban air pollution on cardiac hospital readmissions in survivors of myocardial infarction, a potentially susceptible subpopulation.

Methods And Results: In this European multicenter cohort study, 22,006 survivors of a first myocardial infarction were recruited in Augsburg, Germany; Barcelona, Spain; Helsinki, Finland; Rome, Italy; and Stockholm, Sweden, from 1992 to 2000.

Aerosol particle number concentration measurements in five European cities using TSI-3022 condensation particle counter over a three-year period during health effects of air pollution on susceptible subpopulations.

In this study, long-term aerosol particle total number concentration measurements in five metropolitan areas across Europe are presented. The measurements have been carried out in Augsburg, Barcelona, Helsinki, Rome, and Stockholm using the same instrument, a condensation particle counter (TSI model 3022). The results show that in all of the studied cities, the winter concentrations are higher than the summer concentrations.