180 research outputs found
Reanalysis of two studies with contrasting results on the association between statin use and fracture risk: the General Practice Research Database
No full textBACKGROUND: Two recent case-control studies by Meier et al. and van Staa et al. used the UK General Practice Research Database (GPRD) to examine the association between the use of statins and the risk of fractures, with different results. The objective of the present study was to examine methodological explanations for the discrepant results. METHODS: We created two datasets, which mimicked the previous study designs: a 'selected population' (SP) case-control dataset, with fracture cases matched to controls nested within a selected cohort (Meier et al.), and an 'entire population' (EP) case-control dataset, with both cases and controls sampled from the total GPRD population (van Staa et al.). Cases and controls were matched by gender, age (year of birth or 5 year age bands), and general practice. RESULTS: The study included 131 855 fracture cases. The crude odds ratio (OR) for hip fracture in statin users was 0.37 (95% CI 0.27-0.52) in the SP and 0.54 (95% CI 0.39-0.74) in the EP dataset. This difference was reduced when matching by year of birth, rather than by 5 year age bands: crude ORs were 0.58 (95% CI 0.43-0.79) and 0.61 (95% CI 0.44-0.88), respectively. In the SP dataset, 37% of the cases could be matched by year of birth, while this was achieved for 99% in the 'EP' dataset. The exposure time-window, the selection of confounders, and exclusion of high-risk patients also influenced results. CONCLUSION: Residual confounding by a matching variable and different definitions of the exposure time window explained differences in results. In case-control studies of drug use and fracture risk, broad matching criteria for age should be avoided and the selection of the time-window for exposure should be carefully considered
Risk of fractures in patients with multiple sclerosis: a population-based cohort study.
No full textOBJECTIVE: To examine the risk of fracture in patients with multiple sclerosis (MS) compared with population-based controls. METHODS: A population-based cohort study was performed in the Dutch PHARMO Record Linkage System (1998-2008). Patients with MS (n = 2,415) were matched by year of birth, sex, and practice to up to 6 patients without MS (controls). We used Cox proportional hazards models to estimate the hazard ratio (HR) of fracture in MS. Time-dependent adjustments were made for age, history of disease, and drug use. RESULTS: During follow-up, there were 59 fractures among patients with MS (2.4%) and 227 fractures among controls (1.8%). Patients with MS had a 1.7-fold increased risk of osteoporotic fracture (HR 1.73 [95% confidence interval (CI) 1.18-2.53]) and a 4-fold increased risk of hip fracture (HR 4.08 [95% CI 2.21-7.56]). The risk of osteoporotic fracture was significantly greater for patients with MS who had been prescribed antidepressants (HR 3.25 [95% CI 1.77-5.97]) or hypnotics/anxiolytics (HR 3.40 [95% CI 2.06-5.63]) in the previous 6 months, compared with controls. CONCLUSIONS: Increased awareness of the risk of hip fracture is warranted in patients with MS, especially in those who have recently been prescribed antidepressants or hypnotics/anxiolytics
Update on the Epidemiology of Paget's Disease of Bone
No full textPaget's disease of bone (PDB) is characterized by rapid bone remodeling and the formation of bone that is structurally abnormal. Recent studies have confirmed that both genetic and environmental factors are important in its etiology. Epidemiological studies in Europe and North America have revealed that PDB shows an increasing frequency of occurrence with age and is more prevalent among men than women. There is marked geographic variation in the prevalence of PDB throughout western nations, with the highest rates reported during the 1970s in Britain. Recent studies of the secular trends in PDB suggest declining rates in both prevalence and severity at diagnosis. Thus, the overall age/sex standardized prevalence rate in Britain during the period 1993-1995 was found to be 2.5% among men and 1.6% among women >/=55 years of age. Prevalence rates had fallen by approximately 50% in several of the centers studied, suggesting an environmental contribution to the etiology of this disorder. Similar findings have been reported from other European countries and New Zealand. Recent study of the incidence and clinical manifestations of PDB have emerged from large cohort studies in primary care record linkage resources, such as the General Practice Research Database. Over the period 1988-1999, the incidence rate of clinically diagnosed PDB was found to be 5 per 10,000 person-years among men and 3 per 10,000 person-years among women 75 years of age. The disorder was associated with an increased risk of back pain (RR, 2.1; 95% CI, 1.9-2.3); osteoarthritis (RR, 1.7; 95% CI, 1.5-1.9); and fracture (RR, 1.2; 95% CI, 1.0-1.5). Using life table methodology, the estimated proportion of patients dying within 5 years of follow-up was 32.7% among the cohort with PDB compared with 28.0% among control patient
A review of the methods used to define glucocorticoid exposure and risk attribution when investigating the risk of fracture in a rheumatoid arthritis population
No full textBackground: Glucocorticoid therapy is used widely in patients with rheumatoid arthritis (RA) with good efficacy but concerns about safety including fractures. Estimates of fracture risk for any given patient are complicated by the dynamic pattern of glucocorticoid use, where patients vary in their dose, duration and timing of glucocorticoid use.Objective: To investigate which methods are currently used to attribute fractures to glucocorticoid exposure and investigate whether such methods can consider individual treatment patterns.Results: Thirty-eight studies used five common definitions of risk attribution to glucocorticoid exposure: “current use”, “ever use”, “daily dose”, “cumulative dose” and “time variant”. One study attempted to combine multiple definitions where “cumulative dose” was nested within “daily dose”, covering the effects of dose and duration but not timing. The majority of results demonstrated an equivocal or increased risk of fracture with increased exposure, although there was wide variation, with odds ratios, hazard ratios and relative risks ranging from 0.16 to 8.16. Within definitions there was also variability in the results with the smallest range for “time variant”, 1.07 to 2.8, and the largest for “cumulative dose”, ranging from risk estimates of 0.88 to 8.12.Conclusion: Many studies have looked into the effect of glucocorticoids on fracture risk in patients with RA. Despite this, there is no clear consensus about the magnitude of risk. This is a consequence of the varied analysis models and their different assumptions. Moreover, no current analysis method allows consideration of dose, duration and timing of glucocorticoid therapy, preventing a clear understanding of fracture risk for patients and their individual treatment patterns
Individual fracture risk and the cost-effectiveness of bisphosphonates in patients using oral glucocorticoids
No full textOBJECTIVES: There are few data on the cost-effectiveness of bisphosphonates with oral glucocorticoids (GCs). An individual patient-based pharmaco-economic model was developed. METHODS: Data were obtained from a cohort of oral GC users aged 40+ (n = 190 000) in the UK General Practice Research Database. Individualized fracture and mortality risks were calculated specific for age, sex, daily and cumulative GC dose, indication and other clinical risk factors. UK costs of medication and direct costs of fracture were obtained from National Institute for Clinical Excellence and used to estimate costs per quality-adjusted life-year (QALY) gained and fracture prevented for bisphosphonates in patients treated for 5 yrs with GCs. RESULTS: With the use of 5 mg GCs daily, the cost per one QALY gained with bisphosphonates was 41k UK pounds (95% confidence intervals 22-72k) in women aged <60 [men 40k pounds (29-54k)], 17k pounds (13-24k) in women aged 60-79 [men 43k pounds (31-60k)], 5k pounds(3-6k) in women aged 80+ [men 35k pounds (25-46k)]. With 15 mg GC, these figures were 17k pounds (14-21k), 13k pounds (10-16k) and 15k pounds (9-26k) in women and 22k pounds (17-26k), 34 pounds (23-53k) and 33k pounds (27-42k) in men, respectively. When stratifying by overall fracture risk and life expectancy at the start of GC therapy, cost per QALY increased with decreasing life expectancy. Patients with rheumatoid arthritis had comparatively better cost-effectiveness, given higher fracture risk and better life expectancy. CONCLUSIONS: The cost-effectiveness of bisphosphonates varied substantially. Bisphosphonates can be considered cost-effective in patients with higher fracture risks, such as elderly patients (with a life expectancy over 5 yrs), and younger patients with a fracture history, low body mass index, rheumatoid arthritis or using high GC doses
The use of inhaled corticosteroids in the United Kingdom and the Netherlands
No full textThis study examined the utilisation patterns of inhaled corticosteroids in England/Wales and the Netherlands. Computerised medical records from the GPRD (U. K.) and PHARMO (the Netherlands) databases were used. It included 284 733 English/Welsh and 27 761 Dutch adult patients who were prescribed inhaled corticosteroids during the 10-year study period. Our results showed that, in both study populations, overall use of inhaled corticosteroids increased over the period studied, with its prevalence rising steeply with age and declining in extreme old age. Decreased use of bronchodilators and oral corticosteroids in the early treatment of asthma was noted in our findings. In addition, a trend towards the decreasing use of oral corticosteroids concomitant with inhaled corticosteroid therapy was also observed for both groups. Our study found that only 42.1% of the GPRD and 31.1% of the PHARMO patients received a repeat prescription within the expected duration of the preceding inhaled corticosteroid prescription. In conclusion, our study found many similarities in the prescribing and use of inhaled corticosteroids between the two study populations. The observation of irregular use of inhaled corticosteroid among a substantial number of patients highlights a need for further study into the reasons for irregular use and its consequences on the effectiveness of treatment
Antipsychotic use and the risk of hip/femur fracture: a population-based case-control study
No full textSummary: this case–control study showed that current use of conventional antipsychotics, but not atypical antipsychotics, seems to be associated with an increased risk of a hip/femur fracture, possibly related to the pharmacological properties of conventional antipsychotics. Furthermore, no evidence for a dose effect was found.Introduction: the aim of this study was to assess the risk of hip/femur fracture associated with antipsychotic use, with particular reference to any difference in risk with conventional versus atypical antipsychotics, dose, and pharmacological properties.Methods: a case–control study was conducted using data from the PHARMO Record Linkage System among individuals aged 18 years and older between 1991 and 2002. Cases had a record of a hip or femur fracture, while controls had no evidence of ever having sustained any fracture.Results: most cases were elderly (77.6% aged ?70 years). We found an increased risk for hip/femur fracture associated with the use of antipsychotic drugs. The risk for current users (ORadj 1.68 [1.43, 1.99]) was significantly greater than with past use (ORadj 1.33 [1.14, 1.56]; p?=?0.036). Current use of conventional antipsychotics (ORadj 1.76 [1.48, 2.08]) but not atypical antipsychotics (ORadj 0.83 [0.42, 1.65]) was associated with an increased risk. We did not find evidence for a dose effect.Conclusion: the use of conventional, but not atypical antipsychotics, seems to be associated with an increased risk of hip/femur fracture, possibly related to the pharmacological properties of conventional antipsychotics. However, the numbers of atypical antipsychotic users were small, and therefore this observation needs further attention in other study population
Incidence of fractures among epilepsy patients: a population-based retrospective cohort study in the General Practice Research Database
No full textSummary: Purpose: To compare the incidence of various fractures in a cohort of patients with epilepsy with a reference cohort of patients not having epilepsy.Methods: Patients were included in the epilepsy cohort if they had at least one diagnosis of epilepsy in their medical history and had sufficient evidence of "active" epilepsy (use of antiepileptic drugs, diagnoses) after the practice was included in the General Practice Research Database (GPRD). Two reference patients were sampled for each patient with epilepsy from the same practice. Primary outcome was the occurrence of any fracture during follow-up. Poisson regression analysis was used to estimate incidence density ratios (IDRs).Results: The study population comprised 40,485 and 80,970 patients in the epilepsy and reference cohorts, respectively. The median duration of follow-up was 3 years. The overall incidence rate in the epilepsy cohort was 241.9 per 10,000 person-years. This rate was about twice as high as that in reference cohort: age- and sex-adjusted IDR, 1.89 (95% CI, 1.81–1.98). When comparing IDRs among the different groups of fractures, the highest relative-risk estimate was found for hip and femur fractures (adjusted IDR, 2.79; 95% CI, 2.41–3.24). IDRs were consistently elevated across age and sex groups and across fracture subtypes.Conclusions: The overall risk of fractures was nearly twice as high among patients with epilepsy compared with the general population. The relative fracture risk was highest for hip and femur. Further study is necessary to elucidate whether this elevated risk is due to the disease, the use of antiepileptic drugs, or both
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