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1.
Osteoporos Int ; 33(7): 1579-1589, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35138412

ABSTRACT

The aim of this study was to evaluate the risk of acute myocardial infarction in patients taking osteoporosis medication. Patients were taken from the SIDIAP or CPRD database and were matched using propensity scores. Patients with diabetes and chronic kidney disease taking SERMs were at an increased risk. The results favour the cardiovascular safety of alendronate as a first-line choice for osteoporosis treatment. INTRODUCTION: This study aims to evaluate the comparative safety of anti-osteoporosis drugs based on the observed risk of acute myocardial infarction while on treatment in a primary care setting. METHODS: This is a propensity-matched cohort study and meta-analysis. This study was conducted in two primary care record databases covering UK NHS (CPRD) and Catalan healthcare (SIDIAP) patients during 1995-2014 and 2006-2014, respectively. The outcome was acute myocardial infarction while on treatment. Users of alendronate (reference group) were compared to those of (1) other oral bisphosphonates (OBP), (2) strontium ranelate (SR), and (3) selective oestrogen receptor modulator (SERM), after matching on baseline characteristics (socio-demographics, fracture risk factors, comorbidities, and concomitant drug use) using propensity scores. Multiple imputation was used to handle missing data on confounders and competing risk modelling for the calculation of relative risk (sub-distribution hazard ratios (SHR)) according to therapy. Country-specific data were analysed individually and meta-analysed. RESULTS: A 10% increased risk of acute myocardial infarction was found in users of other bisphosphonates as compared to alendronate users within CPRD. The meta-analysis of CPRD and SIDIAP results showed a 9% increased risk in users of other bisphosphonate as compared to alendronate users. Sensitivity analysis showed SERMS users with diabetes and chronic kidney disease were at an elevated risk. CONCLUSIONS: This study provides additional data on the risk of acute myocardial infarction in patients receiving osteoporosis treatment. The results favour the cardiovascular safety of alendronate as a first-line choice for osteoporosis treatment.


Subject(s)
Bone Density Conservation Agents , Myocardial Infarction , Osteoporosis , Alendronate/adverse effects , Bone Density Conservation Agents/adverse effects , Cohort Studies , Databases, Factual , Diabetes Mellitus/epidemiology , Diphosphonates/adverse effects , Humans , Myocardial Infarction/chemically induced , Myocardial Infarction/epidemiology , Osteoporosis/drug therapy , Primary Health Care , Renal Insufficiency, Chronic/epidemiology , Risk Assessment , Selective Estrogen Receptor Modulators/adverse effects , Thiophenes/adverse effects , United Kingdom/epidemiology
2.
Osteoporos Int ; 31(8): 1487-1497, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32266436

ABSTRACT

Chronic kidney disease (CKD) is a risk factor for fractures. However, in hip fracture patients, CKD G3-G5 was associated with a higher mortality risk and not associated with a higher risk of subsequent non-hip fractures compared to eGFR > 60 ml/min. The higher mortality risk may, as competing risk, explain our findings. INTRODUCTION: Chronic kidney disease (CKD) is a known risk factor for fragility fractures. Patients aged 50+ with a recent fragility fracture have an increased risk of subsequent fractures. Our aim was to evaluate the association between CKD stages G3-G5 versus estimated glomerular filtration rate (eGFR) > 60 ml/min and the risk of a new non-hip fracture or fragility fracture in patients with a first hip fracture. METHODS: Population-based cohort study using the UK general practices in the Clinical Practice Research Datalink. Associations between CKD stage and first subsequent fracture were determined using Cox proportional hazard analyses to estimate hazard ratios (HRs). To explore the potential competing risk of mortality, cause-specific (cs) HRs for mortality were estimated. RESULTS: CKD G3-G5 was associated with a lower risk of any subsequent non-hip fracture (HR: 0.90, 95%CI: 0.83-0.97), but not with the risk of subsequent major non-hip fragility fracture. CKD G3-G5 was associated with a higher mortality risk (cs-HR: 1.05, 95%CI: 1.01-1.09). Mortality risk was 1.5- to 3-fold higher in patients with CKD G4 (cs-HR: 1.50, 95%CI: 1.38-1.62) and G5 (cs-HR: 2.93, 95%CI: 2.48-3.46) compared to eGFR > 60 ml/min. CONCLUSIONS: The risk of a subsequent major non-hip fragility fractures following hip fracture was not increased in patients with CKD G3-G5 compared to eGFR > 60 ml/min. Mortality risk was higher in both hip fracture and non-hip fracture patients with CKD G4 and G5. The higher mortality risk may, as competing risk, explain our main finding of no increased or even decreased subsequent fracture risk after a hip fracture in patients with CKD G3-G5.


Subject(s)
Fractures, Bone , Hip Fractures , Renal Insufficiency, Chronic , Cohort Studies , Female , Fractures, Bone/epidemiology , Frailty , Glomerular Filtration Rate , Hip Fractures/complications , Hip Fractures/epidemiology , Hip Fractures/etiology , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Risk Factors , United Kingdom/epidemiology
3.
Osteoporos Int ; 29(2): 467-478, 2018 02.
Article in English | MEDLINE | ID: mdl-29199359

ABSTRACT

The venous thromboembolism risk among anti-osteoporotics is unknown. In this primary care study, the risk with other bisphosphonates [1.05 (0.94-1.18) and 0.96 (0.78-1.18)], strontium [0.90 (0.61-1.34) and 1.19 (0.82-1.74)], in the UK and Spain respectively, and denosumab [1.77 (0.25-12.66)] and teriparatide [1.27 (0.59-2.71)] in Spain, did not differ versus alendronate. INTRODUCTION: Most of the known adverse drug reactions described for anti-osteoporosis medication (AOM) have been described in studies comparing AOM users to non-users. We aimed to compare the risk of venous thromboembolism (VTE) among incident users of different AOM compared to alendronate (first line therapy). METHODS: Two cohort studies were performed using data from the UK (CPRD) and Spain (BIFAP) primary care records separately. All patients aged ≥ 50 years with at least 1 year of data available and a new prescription or dispensation of AOM (date for therapy initiation) during 2000-2014 (CPRD) or 2001-2013 (BIFAP) were included. Users of raloxifene/bazedoxifene were excluded from both databases. Five exposure cohorts were identified according to first treatment: (1) alendronate, (2) other bisphosphonates, (3) strontium ranelate, (4) denosumab, and (5) teriparatide. Participants were followed from the day after therapy initiation to the earliest of a treated VTE (cases), end of AOM treatment (defined by a refill gap of 180 days), switching to an alternative AOM, drop-out, death, or end of study period. Incidence rates of VTE were estimated by cohort. Adjusted hazard ratios (HR 95%CI) were estimated according to drug used. RESULTS: Overall, 2035/159,209 (1.28%) in CPRD and 401/83,334 (0.48%) in BIFAP had VTE. Compared to alendronate, adjusted HR of VTE were 1.05 (0.94-1.18) and 0.96 (0.78-1.18) for other bisphosphonates, and 0.90 (0.61-1.34) and 1.19 (0.82-1.74) for strontium in CPRD and BIFAP, respectively; 1.77 (0.25-12.66) for denosumab and 1.27 (0.59-2.71) for teriparatide in BIFAP. CONCLUSIONS: VTE risk during AO therapy did not differ by AOM drug use. Our data does not support an increased risk of VTE associated with strontium ranelate use in the community.


Subject(s)
Bone Density Conservation Agents/adverse effects , Venous Thromboembolism/chemically induced , Aged , Aged, 80 and over , Alendronate/adverse effects , Cohort Studies , Denosumab/adverse effects , Diphosphonates/adverse effects , Female , Humans , Male , Middle Aged , Primary Health Care/methods , Risk Assessment/methods , Spain/epidemiology , Teriparatide/adverse effects , Thiophenes/adverse effects , United Kingdom/epidemiology , Venous Thromboembolism/epidemiology
4.
Osteoporos Int ; 28(1): 161-168, 2017 01.
Article in English | MEDLINE | ID: mdl-27722838

ABSTRACT

One-year mortality following a fracture was greater for men compared to women, varied markedly between regions in England with the lowest rates in the London region, and was higher among black women compared to white women. The excess in mortality did not change during the study period. INTRODUCTION: Fractures are associated with increased mortality. With the shift towards an increasingly elderly demography, and so increasing numbers of fractures, the impact of such events on mortality is of key public health importance. Therefore, we aimed to present up-to-date mortality rates following fracture in England. METHODS: This was a population-based study within the Clinical Practice Research Datalink, linked to death certificates (1 January 2001 to 31 December 2011). Subjects were followed from their first fracture (hip, wrist, humerus, clinical spine, ribs, or pelvis) until death for up to 1 year. Rate ratios (RRs) were estimated for 1-year mortality, stratified by sex, 5-year age categories, ethnicity, and geographical region. Excess mortality was presented as standardized mortality ratios (SMRs). RESULTS: One-year mortality following fracture increased with age and was higher for men than women. Black women (RR 1.77; 95 % CI 1.00-3.12) and women of "other" ethnicity (RR 1.59, 95 % CI 1.16-2.16) were at higher risk of death when compared to white women. Mortality was higher among women in almost all regions when compared to the London region, with the highest risk in the East Midlands (37 % higher). The 1-year mortality risk was more than 3-fold higher after fracture as compared to the general population (adjusted SMR: 3.15, 95 % CI 3.09-3.26) and did not change during the study period. Major causes of death were neoplasms, respiratory diseases, and circulatory diseases. CONCLUSION: This study provides up-to-date mortality outcomes following fracture in England and will aid allocation of healthcare provision to those at greatest need.


Subject(s)
Osteoporotic Fractures/mortality , Age Distribution , Aged , Aged, 80 and over , Black People/statistics & numerical data , Cause of Death , Comorbidity , England/epidemiology , Female , Humans , Male , Middle Aged , Sex Distribution , Social Class
5.
Bone ; 94: 50-55, 2017 01.
Article in English | MEDLINE | ID: mdl-27742502

ABSTRACT

INTRODUCTION: Given the expected increase in the number of patients with osteoporosis and fragility fractures it is important to have concise information on trends in prescription rates of anti-osteoporosis drugs (AOD). METHODS: We undertook a retrospective observational study using the UK Clinical Practice Research Datalink (CPRD) in the UK between 1990 and 2012 in subjects 50years or older, stratified by age, sex, geographic region and ethnicity. Yearly prescription incidence rates of any AOD and of each specific AOD were calculated as the number of patients first prescribed these AODs per 10,000person-years (py). RESULTS: In women, yearly rates of first prescription of any AOD increased from 1990 to 2006 (from 2.3 to 169.7 per 10,000py), followed by a plateau and a 12% decrease in the last three years. In men, a less steep increase from 1990 to 2007 (from 1.4 to 45.3 per 10,000py) was followed by a plateau from 2008 onwards. Yearly rates of first prescription of any AOD increased up to the age of 85-89years (248.9 per 10,000py in women and 119.3 in men). There were marked differences between ethnic groups and regions. Bisphosphonates were the most frequently prescribed AODs: etidronate till 2000, and then subsequently alendronate. CONCLUSION: We have demonstrated marked secular changes in rates of anti-osteoporosis drug prescription over the last two decades. The plateau (and decrease amongst women) in rates in recent years, set against an ever ageing population, is worrying, suggesting that the well-documented care gap in osteoporosis treatment persists. The differences in prescription rates by geographic location and ethnicity raise intriguing questions in relation to underlying fracture rates, provision of care and health behaviour. SUMMARY: We studied the prescription incidence of anti-osteoporosis drugs (AOD) from 1990 to 2012 in the UK CPRD. Overall AOD prescription incidence showed a strong increase from 1990 to 2006, followed by a plateau in both sexes and a decrease amongst women in the last three years.


Subject(s)
Bone Density Conservation Agents/administration & dosage , Drug Prescriptions/statistics & numerical data , Ethnicity , Geography , Osteoporosis/drug therapy , Osteoporosis/epidemiology , Sex Characteristics , Administration, Oral , Age Factors , Bone Density Conservation Agents/therapeutic use , Female , Humans , Incidence , Male , United Kingdom/epidemiology
6.
Osteoporos Int ; 27(11): 3197-3206, 2016 11.
Article in English | MEDLINE | ID: mdl-27283403

ABSTRACT

We studied sex-specific incidence rates in a population 50 years or older in the UK. In the period of 1990-2012, the overall rate of fracture did not change, but there were marked secular alterations in the rates of individual fracture types, particularly hip and spine fractures in the elderly. INTRODUCTION: There is increasing evidence of secular changes in age- and sex- adjusted fracture incidence globally. Such observations broadly suggest decreasing rates in developed countries and increasing rates in transitioning populations. Since altered fracture rates have major implications for healthcare provision and planning, we investigated secular changes to age- and sex-adjusted fracture risk amongst the UK population aged 50 years or above from 1990 till 2012. METHODS: We undertook a retrospective observational study using the Clinical Practice Research Datalink (CPRD), which contains the health records of 6.9 % of the UK population. Site-specific fracture incidence was calculated by calendar year for men and women separately, with fracture type categorised according to ICD-9 classification. Linear regression analysis was used to calculate mean annualised change in absolute incidence. For presentational purposes, mean rates in the first 5 years and last 5 years of the period were calculated. RESULTS: Overall fracture incidence was unchanged in both women and men from 1990 to 2012. The incidence of hip fracture remained stable amongst women (1990-1994 33.8 per 10,000 py; 2008-2012 33.5 per 10,000 py; p trend annualised change in incidence = 0.80) but rose in men across the same period (10.8 to 13.4 per 10,000 py; p = 0.002). Clinical vertebral fractures became more common in women (8.9 to 11.8 per 10,000 py; p = 0.005) but remained comparable in men (4.6 to 5.9 per 10,000 py; p = 0.72). Similarly, the frequency of radius/ulna fractures did not change in men (9.6 to 9.6 per 10,000 py; p = 0.25), but, in contrast, became less frequent in women (50.4 to 41.2 per 10,000 py; p = 0.001). Secular trends amongst fractures of the carpus, scapula, humerus, foot, pelvis, skull, clavicle, ankle, patella, and ribs varied according to fracture site and sex. CONCLUSION: Although overall sex-specific fracture incidence in the UK population 50 years or over appears to have remained stable over the last two decades, there have been noticeable changes in rates of individual fracture types. Given that the impact of a fracture on morbidity, mortality, and health economy varies according to fracture site, these data inform the provision of healthcare services in the UK and elsewhere.


Subject(s)
Age Distribution , Fractures, Bone/epidemiology , Sex Distribution , Aged , Aged, 80 and over , Female , Hip Fractures/epidemiology , Humans , Incidence , Male , Middle Aged , Patella , Retrospective Studies , Spinal Fractures/epidemiology , United Kingdom/epidemiology
7.
Bone ; 90: 107-15, 2016 09.
Article in English | MEDLINE | ID: mdl-27268854

ABSTRACT

BACKGROUND: 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.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Fractures, Bone/epidemiology , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Risk Assessment/methods , Confidence Intervals , Dose-Response Relationship, Drug , Humans , Odds Ratio , Risk Factors
8.
Osteoporos Int ; 27(4): 1603-1610, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26630976

ABSTRACT

UNLABELLED: In this retrospective cohort study using the Clinical Practice Research Datalink (CPRD), patients with sarcoidosis have an increased risk of clinical vertebral fractures and when on recent treatment with oral glucocorticoids, also an increased risk of any fractures and osteoporotic fractures. INTRODUCTION: Sarcoidosis is a chronic inflammatory disease, in which fragility fractures have been reported despite normal BMD. The aim of this study was to assess whether patients with sarcoidosis have an increased risk of clinical fractures compared to the general population. METHODS: A retrospective cohort study was conducted using the CPRD. All patients with a CPRD code for sarcoidosis between January 1987 and September 2012 were included. Cox proportional hazards models were used to derive adjusted relative risks (RRs) of fractures in all sarcoidosis patients compared to matched controls, and within the sarcoidosis group according to use and dose of systemic glucocorticoids. RESULTS: Five thousand seven hundred twenty-two sarcoidosis patients (mean age 48.0 years, 51 % females, mean follow-up 6.7 years) were identified. Compared to 28,704 matched controls, the risk of any fracture was not different in patients with sarcoidosis. However, the risk of clinical vertebral fractures was significantly increased (adj RR 1.77; 95 % CI 1.06-2.96) and the risk of non-vertebral fractures was decreased although marginally significant (adj RR 0.87; 95 % CI 0.77-0.99). Compared to sarcoidosis patients not taking glucocorticoids, recent use of systemic glucocorticoids was associated with an increased risk of any fracture (adj RR 1.50; 95 % CI 1.20-1.89) and of an osteoporotic fracture (adj RR 1.47; 95 % CI 1.07-2.02). CONCLUSIONS: Patients with sarcoidosis have an increased risk of clinical vertebral fractures, and when using glucocorticoid therapy, an increased risk of any fractures and osteoporotic fractures. In contrast, the risk of non-vertebral fractures maybe decreased. Further investigation is needed to understand the underlying mechanisms of these contrasting effects on fracture risk.


Subject(s)
Osteoporotic Fractures/etiology , Sarcoidosis/complications , Spinal Fractures/etiology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Cohort Studies , Databases, Factual , Dose-Response Relationship, Drug , Female , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Humans , Male , Middle Aged , Osteoporotic Fractures/epidemiology , Retrospective Studies , Risk Assessment/methods , Sarcoidosis/epidemiology , Sex Distribution , Spinal Fractures/epidemiology , United Kingdom/epidemiology , Young Adult
9.
Osteoporos Int ; 26(7): 1919-28, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25963232

ABSTRACT

UNLABELLED: The probability of initiating with anti-osteoporosis therapy increased from 7 % in 2000 to 46 % in 2010. This improvement was greater for patients over the age of 75 years. Men, those overweight, having dementia or exposed to antipsychotics, sedatives/hypnotics or opioid analgesics were significantly less likely to receive anti-osteoporosis drugs. INTRODUCTION: The objective of this study was to examine trends and determinants of anti-osteoporosis drug prescribing after hip fracture in the UK between 2000 and 2010. METHODS: Data were extracted from the UK Clinical Practice Research Datalink for patients ≥50 years who had a first hip fracture between 2000 and 2010 and who did not currently (≤6 months prior) receive anti-osteoporosis drugs (bisphosphonates, strontium ranelate, parathyroid hormone, calcitonin and raloxifene) (n = 27,542). The cumulative incidence probability of being prescribed anti-osteoporosis drugs within 1 year after hip fracture was estimated by Kaplan-Meier life-table analyses. Determinants for treatment initiation were estimated by Cox proportional hazards models. RESULTS: The probability of being prescribed any anti-osteoporosis drug after hip fracture increased from 7 % in 2000 to 46 % in 2010. This trend was more marked in patients ≥75 years. The increase in prescribing of anti-osteoporosis drugs was complemented by a similar increase in vitamin D/calcium provision. Cumulative incidence of receiving anti-osteoporosis therapy was greater at any given point in time in women (8 % in 2000, 51 % in 2010) compared to men (4 % in 2000, 34 % in 2010). In addition to male gender, multivariable Cox regression identified reduced likelihood of receiving anti-osteoporosis drugs for those being overweight, having dementia and exposed to psychotropic drugs (antipsychotics, sedatives/hypnotics) or opioid analgesics. CONCLUSION: Although the prescribing of anti-osteoporosis drugs after hip fracture has increased substantially since 2000, the overall rate remained inadequate, particularly in men. With the continuing increase in the absolute number of hip fractures, further research should be made into the barriers to optimise osteoporosis management.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Hip Fractures/prevention & control , Osteoporosis/drug therapy , Osteoporotic Fractures/prevention & control , Aged , Aged, 80 and over , Drug Prescriptions/statistics & numerical data , Drug Utilization/statistics & numerical data , Drug Utilization/trends , Female , Hip Fractures/epidemiology , Hip Fractures/etiology , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Osteoporosis/complications , Osteoporosis/epidemiology , Osteoporotic Fractures/epidemiology , Practice Patterns, Physicians'/trends , Primary Health Care/methods , Primary Health Care/trends , Recurrence , Secondary Prevention/methods , Secondary Prevention/trends , United Kingdom/epidemiology
10.
Occup Environ Med ; 72(1): 42-8, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25146191

ABSTRACT

OBJECTIVES: The role of outdoor air pollution in the incidence of chronic obstructive pulmonary disease (COPD) remains unclear. We investigated this question using a large, nationally representative cohort based on primary care records linked to hospital admissions. METHODS: A cohort of 812 063 patients aged 40-89 years registered with 205 English general practices in 2002 without a COPD diagnosis was followed from 2003 to 2007. First COPD diagnoses recorded either by a general practitioner (GP) or on admission to hospital were identified. Annual average concentrations in 2002 for particulate matter with an aerodynamic diameter <10 µm (PM10) and <2.5 µm (PM2.5), nitrogen dioxide (NO2), ozone and sulfur dioxide (SO2) at 1 km(2) resolution were estimated from emission-based dispersion models. Hazard ratios (HRs) per interquartile range change were estimated from Cox models adjusting for age, sex, smoking, body mass index and area-level deprivation. RESULTS: 16 034 participants (1.92%) received a COPD diagnosis from their GP and 2910 participants (0.35%) were admitted to hospital for COPD. After adjustment, HRs for GP recorded COPD and PM10, PM2.5 and NO2 were close to unity, positive for SO2 (HR=1.07 (95% CI 1.03 to 1.11) per 2.2 µg/m(3)) and negative for ozone (HR=0.94 (0.89 to 1.00) per 3 µg/m(3)). For admissions HRs for PM2.5 and NO2 remained positive (HRs=1.05 (0.98 to 1.13) and 1.06 (0.98 to 1.15) per 1.9 µg/m(3) and 10.7 µg/m(3), respectively). CONCLUSIONS: This large population-based cohort study found limited, inconclusive evidence for associations between air pollution and COPD incidence. Further work, utilising improved estimates of air pollution over time and enhanced socioeconomic indicators, is required to clarify the association between air pollution and COPD incidence.


Subject(s)
Air Pollutants/toxicity , Air Pollution/adverse effects , Pulmonary Disease, Chronic Obstructive/epidemiology , Adult , Aged , Aged, 80 and over , Anacardic Acids/toxicity , Cohort Studies , England/epidemiology , Female , General Practice/statistics & numerical data , Hospitalization/statistics & numerical data , Humans , Incidence , Male , Middle Aged , Nitrogen Dioxide/toxicity , Particle Size , Particulate Matter/toxicity , Pulmonary Disease, Chronic Obstructive/etiology , Risk Factors , Sulfur Dioxide/toxicity , Time Factors
11.
Osteoporos Int ; 25(11): 2555-63, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25001987

ABSTRACT

UNLABELLED: The risk of a subsequent major or any fracture after a hip fracture and secular trends herein were examined. Within 1 year, 2.7 and 8.4% of patients sustained a major or any (non-hip) fracture, which increased to 14.7 and 32.5% after 5 years. Subsequent fracture rates increased during the study period both for major and any (non-hip) fracture. INTRODUCTION: Hip fractures are associated with subsequent fractures, particularly in the year following initial fracture. Age-adjusted hip fracture rates have stabilised in many developed countries, but secular trends in subsequent fracture remain poorly documented. We thus evaluated secular trends (2000-2010) and determinants for the risk of a subsequent major (humerus, vertebral, or forearm) and any (non-hip) fracture after hip fracture. METHODS: Patients ≥50 years with a hip fracture between 2000 and 2010 were extracted from the UK Clinical Practice Research Datalink (n = 30,516). Incidence rates, cumulative incidence probabilities, and adjusted hazard ratios (aHRs) were calculated. RESULTS: Within 1 year following hip fracture, 2.7 and 8.4% of patients sustained a major or any (non-hip) fracture, which increased to 14.7 and 32.5% after 5 years, respectively. The most important risk factors for a subsequent major fracture within 1 year were the female gender [aHR 1.90, 95% confidence interval (CI) 1.51-2.40] and a history of secondary osteoporosis (aHR 1.54, 95% CI 1.17-2.02). The annual risk increased during the study period for both subsequent major (2009-2010 vs. 2000-2002: aHR 1.44, 95% CI 1.12-1.83) and any (non-hip) facture (2009-2010 vs. 2000-2002: aHR 1.80, 95% CI 1.58-2.06). CONCLUSION: The risk of sustaining a major or any (non-hip) fracture after hip fracture is small in the first year. However, given the recent rise in secondary fracture rates and the substantial risk of subsequent fracture in the longer term, fracture prevention is clearly indicated for patients who have sustained a hip fracture.


Subject(s)
Hip Fractures/epidemiology , Osteoporotic Fractures/epidemiology , Age Distribution , Aged , Aged, 80 and over , Comorbidity , Female , Humans , Incidence , Male , Middle Aged , Osteoporosis/epidemiology , Recurrence , Risk Assessment/methods , Risk Factors , Sex Distribution , United Kingdom/epidemiology
12.
Eur J Clin Pharmacol ; 70(7): 849-57, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24793010

ABSTRACT

PURPOSE: Drug utilization studies have applied different methods to various data types to describe medication use, which hampers comparisons across populations. The aim of this study was to describe the time trends in antidepressant prescribing in the last decade and the variation in the prevalence, calculated in a uniform manner, in seven European electronic healthcare databases. METHODS: Annual prevalence per 10,000 person-years (PYs) was calculated for 2001-2009 in databases from Spain, Germany, Denmark, the United Kingdom (UK), and the Netherlands. Prevalence data were stratified according to age, sex, antidepressant type (selective serotonin re-uptake inhibitors [SSRIs] or tricyclic antidepressants [TCAs]) and major indications. RESULTS: The age- and sex-standardized prevalence was lowest in the two Dutch (391 and 429 users per 10,000 PYs) and highest in the two UK (913 and 936 users per 10,000 PYs) populations in 2008. The prevalence in the Danish, German, and Spanish populations was 637, 618, and 644 users per 10,000 PY respectively. Antidepressants were prescribed most often in 20- to 60-year-olds in the two UK populations compared with the others. SSRIs were prescribed more often than TCAs in all except the German population. In the majority of countries we observed an increasing trend of antidepressant prescribing over time. Two different methods identifying recorded indications yielded different ranges of proportions of patients recorded with the specific indication (15-57% and 39-69% for depression respectively). CONCLUSION: Despite applying uniform methods, variations in the prevalence of antidepressant prescribing were obvious in the different populations. Database characteristics and clinical factors may both explain these variations.


Subject(s)
Antidepressive Agents/therapeutic use , Practice Patterns, Physicians'/trends , Adult , Aged , Aged, 80 and over , Drug Prescriptions , Drug Utilization Review , Europe , Female , Humans , Male , Middle Aged , Time Factors
13.
Osteoporos Int ; 25(7): 1845-51, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24760245

ABSTRACT

UNLABELLED: The aim of this study was to evaluate fracture risk in patients with Guillain-Barré syndrome (GBS). No association with risk of fracture was observed for GBS patients compared with controls. Only GBS patients using pain treatment had a doubled risk of fracture. INTRODUCTION: Symptoms of Guillain-Barré syndrome (GBS) may vary from mild difficulty in walking to complete paralysis, which may increase the risk of fractures. Therefore, the aim of this study was to evaluate fracture risk in patients with GBS. METHODS: We conducted a retrospective cohort study using the UK Clinical Practice Research Datalink (1987-2012). Each patient with GBS was matched by year of birth, sex, and practice, up to six patients without a history of GBS. Outcome measure was any fracture. RESULTS: There were no associations between GBS and any fracture, adjusted hazard ratio (AHR) 1.01 (95 % confidence interval [CI] 0.77-1.33), or osteoporotic fracture, AHR 0.76 (95 % CI 0.50-1.17), compared with controls. Stratification to gender, age, and duration since diagnosis did not show an association either. Only for GBS patients using pain treatment, risk of fracture was doubled AHR 1.97 (95 % confidence CI 1.21-3.21) compared with controls. The risk of fracture in GBS patients exposed to pain treatment was equivalent to risk of fracture among controls exposed to pain treatment. CONCLUSIONS: No association with risk of fracture was observed for GBS patients compared with controls. Only GBS patients using pain treatment had a doubled risk of fracture, but their risk was equivalent to fracture risk among controls exposed to pain treatment.


Subject(s)
Fractures, Bone/epidemiology , Guillain-Barre Syndrome/epidemiology , Adolescent , Adult , Aged , Analgesics/adverse effects , Analgesics/therapeutic use , Case-Control Studies , Comorbidity , Female , Fractures, Bone/chemically induced , Guillain-Barre Syndrome/drug therapy , Humans , Male , Middle Aged , Osteoporotic Fractures/chemically induced , Osteoporotic Fractures/epidemiology , Risk Assessment/methods , Risk Factors , United Kingdom/epidemiology , Young Adult
14.
J Intern Med ; 275(6): 562-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24635449

ABSTRACT

A solid foundation of evidence of the effects of an intervention is a prerequisite of evidence-based medicine. The best source of such evidence is considered to be randomized trials, which are able to avoid confounding. However, they may not always estimate effectiveness in clinical practice. Databases that collate anonymized electronic health records (EHRs) from different clinical centres have been widely used for many years in observational studies. Randomized point-of-care trials have been initiated recently to recruit and follow patients using the data from EHR databases. In this review, we describe how EHR databases can be used for conducting large-scale simple trials and discuss the advantages and disadvantages of their use.


Subject(s)
Electronic Health Records/organization & administration , Evidence-Based Medicine/methods , Randomized Controlled Trials as Topic , Confounding Factors, Epidemiologic , Documentation/methods , Documentation/standards , Humans , Needs Assessment , Randomized Controlled Trials as Topic/methods , Randomized Controlled Trials as Topic/standards , Research Design
15.
J Intern Med ; 275(6): 590-604, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24581153

ABSTRACT

Inter-individual variability in drug responses is a common problem in pharmacotherapy. Several factors (non-genetic and genetic) influence drug responses in patients. When aiming to obtain an optimal benefit-risk ratio of medicines and with the emergence of genotyping technology, pharmacogenetic studies are important for providing recommendations on drug treatments. Advances in electronic healthcare information systems can contribute to increasing the quality and efficiency of such studies. This review describes the definition of pharmacogenetics, gene selection and study design for pharmacogenetic research. It also summarizes the potential of linking pharmacoepidemiology and pharmacogenetics (along with its strengths and limitations) and provides examples of pharmacogenetic studies utilizing electronic health record databases.


Subject(s)
Electronic Health Records/statistics & numerical data , Genetic Association Studies/methods , Genetic Research , Pharmacogenetics/methods , Humans , Pharmacoepidemiology/methods , Research Design
16.
Osteoporos Int ; 25(1): 385-92, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24221450

ABSTRACT

UNLABELLED: The aim of this study was to determine whether feedback by pharmacists to prescribers of patients eligible for glucocorticoid-induced osteoporosis prophylaxis would stimulate the prescribing of osteoporosis prophylaxis. The intervention did not significantly increase the prescribing of bisphosphonates in the total study population, but a significant increase was seen in men and in the elderly. However, the proportion of bisphosphonate-treated patients remained low. INTRODUCTION: The aim of this study was to determine whether feedback by pharmacists to prescribers of patients eligible for glucocorticoid-induced osteoporosis prophylaxis (GIOP) would stimulate the implementation of the Dutch GIOP guideline. METHODS: This randomised controlled trial included 695 patients who were dispensed ≥675 mg prednisone equivalents without a concomitant bisphosphonate prescription within 6 months before baseline. Pharmacists were asked to contact the physicians of GIOP-eligible patients in the intervention group to suggest osteoporosis prophylaxis. The primary endpoint was a bisphosphonate prescription. Secondary endpoints were a prescription of calcium supplements, vitamin D or any prophylactic osteoporosis drug (bisphosphonate, calcium supplements, vitamin D). RESULTS: The group assigned to the intervention was slightly younger than the control group (68.7 ± 15.4 vs. 65.9 ± 16.9 years, p = 0.02) and used hydrocortisone more often (7.0% vs. 3.1%, p = 0.02). Within 6 months, the intervention did not significantly increase the prescribing of bisphosphonates (11.4% after intervention vs. 8.0% for controls; hazard ratio [HR] 1.47, 95% confidence interval [CI] 0.91-2.39). However, subgroup analyses showed a significant increase for the primary endpoint in men (12.8% vs. 5.1%, HR 2.53, 95% CI 1.11-5.74) and patients ≥70 years (13.4% vs. 4.9%, HR 2.88, 95% CI 1.33-6.23). The prescribing of calcium and vitamin D was not significantly altered. CONCLUSION: This study showed that active identification of patients eligible for GIOP by pharmacists did not significantly increase the prescribing of bisphosphonates in the total study population, but there was an increase in men and the elderly. However, the proportion of GIOP-treated patients remained low.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Diphosphonates/therapeutic use , Feedback , Glucocorticoids/adverse effects , Osteoporosis/prevention & control , Pharmacists/psychology , Aged , Drug Prescriptions/statistics & numerical data , Drug Utilization/statistics & numerical data , Female , Guideline Adherence , Humans , Interprofessional Relations , Male , Middle Aged , Netherlands , Osteoporosis/chemically induced , Pharmacies/organization & administration , Practice Guidelines as Topic
17.
Osteoporos Int ; 25(4): 1275-83, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24297094

ABSTRACT

UNLABELLED: The incidence of clinical fractures and the associated factors were assessed in patients with systemic lupus erythematosus (SLE) versus matched controls. We found an increased fracture risk in SLE patients compared to controls. Glucocorticoid use, longer disease duration, neuropsychiatric disease complications and previous osteoporotic fractures were identified as associated factors. INTRODUCTION: The aims of this study were to estimate the risk of clinical fractures in patients with SLE versus matched controls and to evaluate the risk factors associated with clinical fractures in SLE. METHODS: This is a population-based cohort study using the Clinical Practice Research Datalink (from 1987-2012). Each SLE patient (n = 4,343) was matched with up to six controls (n = 21,780) by age and sex. Clinical fracture type was stratified according to the WHO definitions into osteoporotic and non-osteoporotic fracture. Cox proportional hazards calculated relative rates (RR) of clinical fracture and time interaction terms to evaluate the timing patterns of fracture. Clinical fracture rates in SLE patients, stratified by age, gender, type of fracture, disease duration and therapy variables, were compared with those rates in controls. RESULTS: Follow-up durations were 6.4 years in SLE patients and 6.6 years in controls. SLE patients had a 1.2-fold increased clinical fracture risk compared to controls (adjusted RR = 1.22, 95% CI = 1.05-1.42), and the risk further increased with a longer disease duration. Glucocorticoid (GC) use in the previous 6 months raised the risk of clinical fracture (adjusted RR = 1.27, 95% CI = 1.02-1.58). Cerebrovascular events, seizures and previous osteoporotic fractures were identified as predictors of clinical fractures. CONCLUSIONS: We found an increased risk of clinical fracture in SLE patients compared to controls. GC use in the previous 6 months and longer disease duration are associated with the increased fracture risk in SLE. Patients with neuropsychiatric organ damage or previous osteoporotic fractures are also at increased risk of the occurrence of clinical fractures.


Subject(s)
Fractures, Bone/etiology , Lupus Erythematosus, Systemic/complications , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Case-Control Studies , Databases, Factual , Drug Administration Schedule , Female , Fractures, Bone/epidemiology , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Humans , Incidence , Lupus Erythematosus, Systemic/epidemiology , Male , Middle Aged , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/etiology , Risk Factors , Sex Distribution , United Kingdom/epidemiology , Young Adult
18.
J Thromb Haemost ; 11(4): 642-50, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23387806

ABSTRACT

BACKGROUND: Long-term risk of venous thromboembolism (VTE) following total hip or knee replacement (THR/TKR) compared with controls has not been studied extensively, and the long-term influence of outpatient anticoagulant use on VTE risk remains unknown. The objectives were to evaluate long-term VTE risk following THR/TKR compared with matched controls, and to investigate effect modification by prolonged outpatient vitamin K antagonist use. METHODS: A Danish retrospective nationwide cohort study was conducted. All patients undergoing primary THR/TKR (n = 95,227) between 1998 and 2007 were selected, each matched by age, sex and region with three controls (no THR/TKR). Patients were stratified by prolonged outpatient vitamin K antagonist use in the previous 3 months (in a time-dependent manner). All subjects were followed for VTE, and Cox models were used to calculate disease and medication history adjusted hazard ratios (HRs). RESULTS: Within 6 weeks following surgery, a 13-fold increased risk of VTE was found for THR (adj. HR 12.9; 95% CI 11.2-14.7), and a 14-fold elevated risk for TKR (adj. HR 13.6; 95% CI 11.0-16.7), compared with matched controls. The risk remained substantially increased for at least 4 months following THR/TKR. Within this period, prolonged outpatient vitamin K antagonist use reduced the increase in VTE risk by 69% for THR and 54% for TKR. CONCLUSION: The risk of VTE remains substantially elevated for at least 4 months following THR/TKR; this is well beyond the recommended duration of anticoagulant use. The increase in VTE risk is less pronounced in prolonged outpatient vitamin K antagonist users.


Subject(s)
Anticoagulants/adverse effects , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Knee/adverse effects , Outpatients , Venous Thromboembolism/etiology , Vitamin K/antagonists & inhibitors , Aged , Aged, 80 and over , Anticoagulants/administration & dosage , Case-Control Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors
19.
J Thromb Haemost ; 11(1): 107-15, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23088617

ABSTRACT

BACKGROUND: Anticoagulation control is often summarized using the percentage of time spent in a therapeutic range (TTR). This method does not describe the timing and severity of fluctuations in the International Normalised Ratio (INR). OBJECTIVE: To evaluate whether the TTR method can be improved by considering the patterns of INR over time. METHODS: The cohort included adults aged 40+ years with atrial fibrillation (AF) and laboratory records of INR as recorded in the UK Clinical Practice Research Datalink. Statistical clustering techniques based on simple INR measures were used to describe the patterns of INR. Nested case-control studies calculated the odds ratios (ORs) for the risk of stroke, bleeding and mortality with TTR and different INR patterns. It was also evaluated whether cluster analyses improved the prediction of outcomes over TTR. RESULTS: A number of 27 381 patients were studied with a mean age of 73 years. The OR for mortality was 3.76 (95% confidence interval [CI] 3.03-4.68) in patients with < 30% TTR compared with patients with 100% TTR. INR patterns were found to be best described by six different clusters. The cluster with the most unstable pattern was associated with the largest risk of mortality (OR 10.7, 95% CI 8.27-13.85) and stroke (OR 3.42, 95% CI 2.08-5.63). INR measures that predicted death independent of the TTR-included absolute difference between two subsequent INR measurements and change relative to the mean over time. CONCLUSION: Cluster analysis of INR patterns improved the prediction of clinical outcomes over TTR and may help to identify warfarin users who need additional anticoagulation monitoring.


Subject(s)
Anticoagulants/adverse effects , Atrial Fibrillation/drug therapy , Blood Coagulation/drug effects , Hemorrhage/chemically induced , Stroke/drug therapy , Adult , Aged , Aged, 80 and over , Atrial Fibrillation/blood , Atrial Fibrillation/complications , Atrial Fibrillation/mortality , Case-Control Studies , Cluster Analysis , Drug Monitoring/methods , Female , Hemorrhage/blood , Hemorrhage/mortality , Humans , International Normalized Ratio , Logistic Models , Male , Middle Aged , Odds Ratio , Predictive Value of Tests , Registries , Risk Assessment , Risk Factors , Stroke/blood , Stroke/etiology , Stroke/mortality , Time Factors , Treatment Outcome , United Kingdom
20.
Neurology ; 78(24): 1967-73, 2012 Jun 12.
Article in English | MEDLINE | ID: mdl-22592374

ABSTRACT

OBJECTIVE: 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.


Subject(s)
Fractures, Bone/complications , Multiple Sclerosis/complications , Adolescent , Adult , Aged , Cohort Studies , Databases, Factual , Female , Hip Fractures/complications , Humans , Male , Middle Aged , Netherlands , Osteoporotic Fractures/complications , Risk , Risk Factors
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