The economic burden of preventable adverse drug reactions: a systematic review of observational studies

Introduction: Adverse drug reactions (ADRs) are an important cause of morbidity and mortality worldwide. They are associated with healthcare costs due to hospital admissions or prolonged length of stay, as well as additional interventions. The aim of this study was to conduct a systematic review of observational studies to evaluate the economic impact of preventable ADRs.

Areas covered: Published observational research investigating the cost of preventable ADRs in Western countries (limited to the USA and European countries).

Expert opinion: Several reviews have been carried out in the field of the ADR epidemiology but fewer reviews have investigated the economic impact of ADRs, and at the time of writing, none has focused on preventable ADRs. The reason why future research should focus on the costs of preventable ADRs is that both the costs and the negative clinical outcomes are preventable, and as such, are a key point of public health policy action. Nevertheless, the present review highlights an important and sobering limitation of published research on the cost of preventable ADRs, of which the major limitation is the heterogeneity in methods and in reporting which limit what can be known through the summarizing work of a systematic review.     

The effects of recombinant-DNA-derived interferons on the growth of myeloid progenitor cells

Interferons (IFNs) have been shown to have significant effects on hematopoietic cell growth. Previous studies defining these effects have utilized mouse and human alpha-, beta-, and gamma-IFN isolated from supernatants of stimulated cells. Despite purification, the possible presence of other lymphokines and soluble factors remains a concern. In this study, the effects of gene-cloned alpha- and gamma-IFN on colony- forming units of granulocyte/macrophage (CFU-GM) progenitors cultured from the peripheral blood of normal volunteers were examined. In addition, blast cell colonies from one patient with acute myelogenous leukemia (AML) were studied. The growth of normal CFU-GM and AML blast cell colonies was inhibited in a dose-dependent manner by gamma- and alpha-IFN. gamma-IFN was ten to 100 times more potent than alpha-IFN in that this species of IFN reduced colony formation by greater than 50% at concentrations of less than 15 antiviral U/mL. The effects of gamma- IFN were neutralized by a monoclonal antibody specific for gamma-IFN. These in vitro studies indicate that human gamma-IFN may be an important modulator of myelopoiesis. Although these data indicate a possible efficacy of gamma-IFN in the treatment of AML, the in vitro results should be considered for their in vivo significance.     

Ischemic heart disease in patients from Northwest Spain with biopsy proven giant cell arteritis. A population based study

OBJECTIVE: To assess the incidence, mortality, and predictors of ischemic heart disease (IHD) in patients from the Lugo region of Northwest Spain with biopsy-proven giant cell arteritis (GCA). METHODS: Retrospective study of patients with biopsy-proven GCA diagnosed from 1981 to 2001 at the single hospital for a population of 250,000 people. A survival analysis was performed. Hazard ratios and standardized mortality ratio (SMR) as well as predictors of IHD in patients with biopsy-proven GCA were also assessed. RESULTS: Nineteen (9%) of the 210 patients with biopsy-proven GCA diagnosed during the period of study had IHD. The incidence of IHD in patients with GCA was 12.6/1000 person-years at risk (95% CI 6.9-21.0). During the study period 1981-2000 the population aged > or = 50 years in Lugo was roughly 100,000, and the mortality rate due to IHD in patients with GCA for that population was 8/100,000. The SMR in patients with GCA due to IHD was 1.62 (95% CI 0.70-3.20). Mortality in patients with GCA who had IHD was higher than in those patients without IHD (age and sex adjusted hazard ratio 2.81, 95% CI 1.51-5.21; p = 0.001). Age (hazard ratio 1.15), hypertension (hazard ratio 2.51), and abnormal temporal artery on physical examination (hazard ratio 0.36) at the time of diagnosis of GCA were the best predictors of IHD over the followup period in patients with biopsy-proven GCA. CONCLUSION: Our observations suggest that mortality due to IHD in patients from Lugo with GCA is not much higher than that reported in the Spanish population aged 50 years and older. However, mortality in patients with GCA with IHD is higher than in GCA patients without IHD.     

High-grade C-reactive protein elevation correlates with accelerated atherogenesis in patients with rheumatoid arthritis

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at greater risk of developing cardiovascular events compared with individuals without RA. Increased risk for cardiovascular disease in these patients is a consequence of atherosclerosis. Case-control studies have shown that increased intima-media thickness (IMT) of the common carotid artery is an indicator of generalized atherosclerosis. Some investigators have suggested that the development of atherosclerosis in RA may be related to the magnitude and chronicity of the systemic inflammation. We examined the relationship between carotid IMT to C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), which are the most commonly assessed markers of inflammatory response in patients with RA. METHODS: Retrospective review of CRP and ESR values in 47 patients with longterm actively treated (at least 5 years) RA without clinically evident atherosclerosis or its complications, who had been studied for carotid IMT with high resolution B-mode ultrasound. RESULTS: No correlation between ESR and carotid IMT was observed. However, a correlation was found between the maximum CRP values and the carotid IMT (p = 0.009). The distribution of patients in 4 quartiles according to the average CRP values showed significant differences in the carotid IMT (p = 0.03). Those exhibiting the highest mean CRP values (quartile 4) had greater carotid IMT. There was no correlation between CRP at the time of disease diagnosis or at the time of the ultrasound study and the carotid IMT. CONCLUSION: Our study confirms that the magnitude and chronicity of the inflammatory response measured by CRP correlates directly with the presence of atherosclerosis in patients with RA.