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1.
Osteoporos Int ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31418061

RESUMO

We investigated the incidence trend in all major osteoporotic fractures for the whole country of Denmark between 1995 and 2010. Hip and other osteoporotic fractures declined for the general population and especially among women. But, we observed some increasing trend among men which needs more attention. PURPOSE: The trend in osteoporotic fractures is varied across the globe, and there is no updated information in the case of Denmark for all major osteoporotic fractures (MOF). Thus, we investigated the incidence rates (IRs) of MOF among 50+ adults in Denmark over the period 1995-2010. METHODS: A series of cross-sectional analyses was done using the Danish National Health Service Register. Participants were 50+ adults in the full country Denmark with a MOF between 1995 and 2010. Gender- specific IRs of MOF per 10,000 person years (PYs) were estimated, in addition to IRs of individual fracture sites (hip, vertebrae, humerus, and radius/ulna), and women-to-men IR ratios for MOF. RESULTS: A general decline was observed in IRs of MOF for the whole population (from 169.8 per 10,000 PYs in 1995, to 148.0 in 2010), which was more pronounced among women. Thirty-one and nineteen percent of decline was observed in hip fracture rates among women and men, respectively. The trend in clinical vertebral fracture was slightly decreasing for women and increasing for men. The women-to-men rate ratio of MOF decreased noticeably from 2.93 to 2.72 during study period. CONCLUSIONS: We observed declining trends in MOF and hip fracture for both sexes. However, a lower rate of decrease of hip fracture and an increasing trend in vertebral fracture was noticed among men. Considering our observations and the major economic burden that accompanies this devastating disease, more attention should be paid to MOF, especially in men.

2.
Arch Osteoporos ; 14(1): 77, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286270

RESUMO

The publisher has retracted this article [1] from Archives of Osteoporosis in order to publish in Osteoporosis International as originally intended by the authors and the Editors of Osteoporosis International. Springer Nature apologizes to readers and the authors.

3.
Pharmacoepidemiol Drug Saf ; 27(11): 1191-1199, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30264901

RESUMO

PURPOSE: It remains unclear whether eosinophilia is useful for in guiding inhaled corticosteroid (ICS) therapy in chronic obstructive pulmonary disease (COPD) patients. The goal of this study is to evaluate the risk of acute exacerbations, COPD-related hospitalisations/accident and emergency visits, and all-cause mortality with various levels of eosinophil counts among COPD patients using ICS. METHODS: A cohort study was conducted using the UK Clinical Practice Research Datalink. Patients were aged 40+ and had COPD (n = 32 693). Current users of ICS were stratified by relative and absolute eosinophil counts to determine the risk of outcomes with blood eosiniphilia using Cox regression analysis. RESULTS: Among COPD patients, current use of ICS was not associated with a reduced risk of acute COPD exacerbations, COPD-related hospitalisations/accident and emergency visits, and all-cause mortality. Stratification of ICS use by absolute or relative eosinophil counts did not result in significant differences in risk of COPD exacerbations or hospitalisations/accident and emergency visits. However, all-cause mortality was reduced by 12% to 24% among patients with eosinophilia. CONCLUSIONS: COPD-related acute exacerbations or hospitalisations/accident and emergency visits were not reduced with eosinophilia among users of ICS with COPD. However, all-cause mortality was reduced by 12% to 24%. These findings are potentially important and require further evaluation in prospective studies.

4.
Arch Osteoporos ; 13(1): 91, 2018 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-30151659

RESUMO

We investigated the incidence trend in all major osteoporotic fractures for the whole country of Denmark between 1995 and 2010. Hip and other osteoporotic fractures declined for the general population and especially among women. But, we observed some increasing trend among men which needs more attention. PURPOSE: The trend in osteoporotic fractures is varied across the globe, and there is no updated information in the case of Denmark for all major osteoporotic fractures (MOF). Thus, we investigated the incidence rates (IRs) of MOF among 50+ adults in Denmark over the period 1995-2010. METHODS: A series of cross-sectional analyses was done using the Danish National Health Service Register. Participants were 50+ adults in the full country Denmark with a MOF between 1995 and 2010. Gender- specific IRs of MOF per 10,000 person years (PYs) were estimated, in addition to IRs of individual fracture sites (hip, vertebrae, humerus, and radius/ulna), and women-to-men IR ratios for MOF. RESULTS: A general decline was observed in IRs of MOF for the whole population (from 169.8 per 10,000 PYs in 1995, to 148.0 in 2010), which was more pronounced among women. Thirty-one and nineteen percent of decline was observed in hip fracture rates among women and men, respectively. The trend in clinical vertebral fracture was slightly decreasing for women and increasing for men. The women-to-men rate ratio of MOF decreased noticeably from 2.93 to 2.72 during study period. CONCLUSIONS: We observed declining trends in MOF and hip fracture for both sexes. However, a lower rate of decrease of hip fracture and an increasing trend in vertebral fracture was noticed among men. Considering our observations and the major economic burden which accompanies this devastating disease, more attention should be paid to MOF, especially in men.

5.
Br J Clin Pharmacol ; 84(11): 2551-2561, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29975795

RESUMO

AIMS: Domperidone is used to treat gastrointestinal symptoms in patients with Parkinson's disease (PD) and is linked to an increased risk of mortality. We sought to examine the risk of all-cause mortality associated with domperidone exposure in PD. METHODS: We conducted a cohort study using data from the Clinical Practice Research Datalink database (1987-2011). The first recorded PD diagnosis defined index date. Time-dependent Cox proportional hazards models estimated hazard ratios (HRs) of all-cause mortality associated with domperidone use. PD patients were stratified by domperidone use (current/recent/past), with never used as the referent. Current domperidone users were stratified by daily dose, domperidone duration and other anti-Parkinson's medications. A secondary analysis compared PD patients to matched (1:1) non-PD patients. RESULTS: A total of 5114 PD patients were identified. Current use of domperidone among PD patients was associated with a two-fold increase in all-cause mortality (HRadj  = 2.00, 95% confidence interval [CI]: 1.64-2.45), as compared to patients never exposed to domperidone. All-cause mortality risk was highest in those starting domperidone in the previous month [HRadj  = 2.97, 95% CI: 2.06-4.27]. When compared to matched non-PD patients, PD was associated with a 43% increased risk of all-cause mortality, yet this increased to a 2.4-fold increased risk among PD patients currently using domperidone. CONCLUSION: Current use of domperidone was associated with a two-fold increased mortality risk in PD patients, as compared to PD patients that never used domperidone. The risk is highest in the first month of use and does not appear to be attributable to PD alone.

6.
Rheumatology (Oxford) ; 57(9): 1641-1650, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29893941

RESUMO

Objectives: When urate lowering therapy is indicated in patients with gout, medication adherence is essential. This study assesses non-persistence and non-adherence in patients with newly diagnosed gout, and identifies factors associated with poor medication adherence. Methods: A retrospective data analysis was performed within the UK Clinical Practice Research Datalink (1987-2014) among incident gout patients, aged ⩾40 years and starting allopurinol (n = 48 280). The proportion of patients non-persistent (a first medication gap of ⩾90 days) after 1 and 5 years, and median time until a first 90-day gap was estimated using Kaplan-Meier statistics in those starting allopurinol and restarting after a first interruption. Non-adherence (proportion of days covered <80%) over the full observation period was calculated. Multivariable Cox- or logistic regressions assessed factors associated with non-persistence or non-adherence, respectively. Results: Non-persistence increased from 38.5% (95% CI: 38.1, 38.9) to 56.9% (95% CI: 56.4, 57.4) after 1 and 5 years of initiation. Median time until a first 90-day gap was 1029 days (95% CI: 988, 1078) and 61% were non-adherent. After a first gap, 43.3% (95% CI: 42.7, 43.9) restarted therapy within 1 year, yet only 52.3% (95% CI: 51.4, 53.1) persisted for 1 year. Being female and a current smoker increased the risk for non-persistence and non-adherence, while older age, overweight, receiving anti-hypertensive medication or colchicine and suffering from dementia, diabetes or dyslipidaemia decreased the risk. Conclusion: Medication adherence among gout patients starting allopurinol is poor, particularly among females and younger patients and patients with fewer comorbidities. Medication adherence remains low in those reinitiating after a first gap.


Assuntos
Alopurinol/uso terapêutico , Gota/tratamento farmacológico , Adesão à Medicação , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Feminino , Seguimentos , Gota/metabolismo , Supressores da Gota/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Ácido Úrico/metabolismo
7.
Cancer Epidemiol ; 54: 104-111, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29705628

RESUMO

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have been shown to have higher incidences of liver, pancreatic, and colorectal cancer compared to non-diabetic individuals. Current evidence is conflicting for other gastrointestinal (GI) cancers. Therefore, we aimed to determine incidence rates (IRs) of all GI cancers in patients with and without T2DM. METHODS: A cohort study was performed using the UK Clinical Practice Research Datalink (1988-2012). A cohort of antidiabetic drug users was matched at baseline to a non-diabetic cohort, by age, sex, and practice. Crude IRs and 95% confidence intervals (95% CI) of GI cancers per 100,000 person-years were calculated stratified by age, sex, and calendar year. RESULTS: 333,438 T2DM and 333,438 non-diabetic individuals were analyzed. IRs of liver (IR 26, 95% CI 24-28 vs. 8.9, 95% CI 7.7-10), pancreatic (IR 65, 95% CI 62-69 vs. 31, 95% CI 28-34), and colon cancer (IR 119, 95% CI 114-124 vs. 109, 95% CI 104-114) were significantly higher in the diabetic compared to the non-diabetic cohort, whereas the IR of oesophageal cancer was significantly lower (IR 41, 95% CI 39-44 vs. 47, 95% CI 44-51). Sex-specific IRs of colon cancer remained significantly higher in men with T2DM, and IRs of esophageal cancer remained significantly lower in women with T2DM. CONCLUSION: In this study, T2DM patients were shown to have higher crude IRs of liver, pancreatic and colon cancer, but not of gastric, biliary, and rectal cancer. Moreover, the lower observed IRs of oesophageal cancer in diabetic patients warrants further investigation.

8.
Arch Osteoporos ; 13(1): 30, 2018 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-29552730

RESUMO

We examined the effect of cumulative exposure to high doses of oral glucocorticoids on fracture risk. Compared to short-course users (daily dose ≥ 15 mg + cumulative < 1 g), heavy users (daily dose ≥ 15 mg + cumulative dose ≥ 1 g) had the highest risk of fracture. These patients should be monitored for fracture management strategies. PURPOSE: The effect of cumulative exposure to high daily doses of oral glucocorticoids on fracture risk remains debated. We therefore aimed to examine the hip fracture risk associated with short courses and heavy use of high-dosed oral glucocorticoids. METHODS: We conducted a population-based case-control study using the Danish National Health Service data, 1996-2011. Cases were those aged ≥ 18 years who sustained a hip (primary outcome) fracture (n = 81,342). Vertebral and forearm fractures were considered in secondary analyses. Controls (matched 1:1) were those without a fracture. Average daily dose (DD) and total cumulative dose (CD) were calculated among current oral glucocorticoid users. Among patients with a high daily dose (DD ≥ 15 mg), we identified short-course users as those with a CD < 1 g and heavy users as those with a CD ≥ 1 g. We estimated adjusted odds ratio (adj.OR) of fracture with current glucocorticoid use compared to never-use, using conditional logistic regression. RESULTS: A high DD (≥ 15 mg) and high CD (≥ 1 g) were independently associated with an increased hip fracture risk (adj.OR 2.5; 95% CI 2.2-2.9; adj.OR 1.6; 95% CI 1.5-1.8, respectively). However, the risk was substantially increased among heavy users (DD ≥ 15 mg and CD ≥ 1 g: adj.OR 2.9; 95% CI 2.5-3.4) as compared to short-course users (DD ≥ 15 mg and CD < 1 g: adj.OR 1.4; 95% CI 1.1-1.9). Associations were stronger for vertebral fractures, yet little association was identified for forearm fractures. CONCLUSION: Among patients receiving a high DD (≥ 15 mg), heavy users (≥ 1 g CD) showed the most substantial increase in hip fracture risk. Among those receiving high DD, a threshold of 1 g CD may identify heavy users that are candidates for focused fracture management services.

9.
Bone ; 110: 238-243, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29462672

RESUMO

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is characterised by persistent airflow obstruction and respiratory symptoms. While short course systemic GCs are prescribed in patients with acute COPD exacerbations, little is known of the risk of fractures with intermittent exposure to high-dose GC and the effect of proxies of disease severity. METHODS: A case-control study was conducted using the Danish National Hospital Discharge Registry (NHDR) between January 1996 to December 2011. Conditional logistics regression models were used to derive adjusted odds ratios (OR) risk of fractures in subjects with COPD stratified by intermittent high-dose, and proxies of disease severity. RESULT: A total of 635,536 cases and the same number of controls were identified (mean age 67.5±13.8, 65% female). COPD patients with intermittent use of high average daily dose oral glucocorticoids did not have an increased risk of any, osteoporotic, hip or clinically symptomatic vertebral fracture compared to non-COPD patients (adj. OR 0.65; 95% CI: 0.50-0.86, 0.70; 95% CI: 0.70-0.99, 1.17; 95% CI: 0.59-2.32, 1.98; 95% CI: 0.59-6.65 respectively). We identified an elevated risk of osteoporotic fracture among patients who visited the emergency unit (adj. OR 1.47; 95% CI 1.20-1.79) or were hospitalised in the past year for COPD (adj. OR 1.76; 95% CI 1.66-1.85). Current GC use among COPD patients was associated with an increased risk of osteoporotic, hip and clinically symptomatic vertebral fractures compared to patients without COPD. CONCLUSION: Intermittent high-dose GCs was not associated with an increased risk of any, osteoporotic, hip or clinically symptomatic vertebral fractures in patients with COPD. Current GC use was however associated with an increased risk of hip and clinically symptomatic vertebral fractures. Therefore, emphasis on prophylactic treatment of fractures may not be essential in patients with COPD receiving intermittent dose of GCs, whereas this should be considered for high-dose long-term users with advanced COPD disease stage, postmenopausal women and men over 40years.

10.
Diabetes Obes Metab ; 20(4): 1056-1060, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29171906

RESUMO

We investigated the association between the current use of individual sulphonylureas and the risk of a first-ever acute myocardial infarction (AMI) and all-cause mortality, in a population-based cohort study, using primary care data from the Clinical Practice Research Datalink database (2004-2012). New users (N = 121 869), aged ≥18 years, with at least one prescription for a non-insulin antidiabetic agent were included. The first prescription defined start of follow-up. Time-dependent Cox proportional hazard models were used to estimate the risk of a first-ever AMI and all-cause mortality associated with the use of individual sulphonylureas, and other non-insulin glucose-lowering drugs. No differences in risk of a first-ever AMI (adjusted hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.70-1.50) or all-cause mortality (adjusted HR 0.97, 95% CI 0.80-1.17) were observed when comparing gliclazide use with non-gliclazide sulphonylurea use. Similar results were found for each individual sulphonylurea. As evidence is accumulating that gliclazide is no safer than other sulphonylureas, current guidelines suggesting superiority should be carefully evaluated.

11.
Cancer Prev Res (Phila) ; 10(5): 290-297, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28274936

RESUMO

Previous studies on metformin use and gastrointestinal (GI) cancer risk have yielded inconclusive results on metformin's chemoprotective effects. We aimed to evaluate GI cancer risk in users of metformin in The Netherlands using a time-varying approach in a large population-based database. A cohort study was performed using the NCR-PHARMO database. Patients using ≥1 non-insulin antidiabetic drug (NIAD) during 1998 to 2011 were included (N = 57,621). Exposure to NIADs was modeled time-varyingly. Cox regression analysis estimated HRs of GI cancers in current metformin users versus current users of other NIADs. Covariables included age, sex, drugs known to impact cancer risk, history of hospitalization, and starting year of follow-up. A sensitivity analysis was performed, applying a new-user design. Current use of metformin was not associated with a decreased risk of GI cancer [HR, 0.97; 95% confidence interval (CI), 0.82-1.15] or specific GI cancer sites. The sensitivity analysis yielded comparable results. No decreasing trends were observed with increasing cumulative dose of metformin [HR 1.05, 95% CI, 0.85-1.28; HR 0.89, 95% CI, 0.73-1.10; HR 0.96, 95% CI, 0.77-1.19 for dose tertiles low (<405 g), medium (405-999 g), and high (≥999 g)]. In contrast, an increased risk of pancreatic cancer was found in current users of metformin plus insulin (HR, 4.90; 95% CI, 2.64-9.10). In conclusion, no decreased risk of GI cancer was found in current metformin users compared with current users of other NIADs. Variations in the exposure definition of metformin use may be one of the explanations of previously found reduced cancer risks in metformin users. Cancer Prev Res; 10(5); 290-7. ©2017 AACR.


Assuntos
Neoplasias Gastrointestinais/epidemiologia , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Adulto , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos
12.
Br J Clin Pharmacol ; 83(8): 1835-1843, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28326589

RESUMO

AIM: Direct-acting oral anticoagulants (DOACs) have become available for the prevention of stroke in patients with atrial fibrillation (AF). Conflicting results have been published on the risk of acute myocardial infarction (AMI) with the use of DOACs in comparison with vitamin K antagonists (VKAs). The objective of the present study was to evaluate the risk of AMI in patients with AF who are exposed to either VKAs, DOACs or low-dose (< 325 mg) aspirin. METHODS: We conducted a population-based cohort study using data from the Clinical Practice Research Datalink (2008-2014). The study population (n = 30 146) consisted of all patients ≥18 years with a diagnosis of AF who were new users of VKAs, DOACs (rivaroxaban and dabigatran) or aspirin. Cox proportional hazards models were used to estimate the hazard ratio (HR) of AMI for users of DOACs or aspirin vs. VKA. Adjustments were made for age, gender, lifestyle, risk factors, comorbidity and other drugs. RESULTS: The risk of AMI was doubled when we compared current use of DOACs with current use of VKAs [adjusted HR 2.11; 95% confidence interval (CI) 1.08, 4.12] and for current users of aspirin vs. current VKA users (adjusted HR 1.91; 95% CI 1.45, 2.51). CONCLUSIONS: There is a twofold increase in the risk of AMI for users of DOACs, in comparison with VKAs, in AF therapy. In addition, the results suggested that in patients with AF, the incidence of AMI is higher during aspirin monotherapy than during the use of VKAs.


Assuntos
Anticoagulantes/farmacologia , Fibrilação Atrial/tratamento farmacológico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação de Plaquetas/farmacologia , Administração Oral , Idoso , Anticoagulantes/uso terapêutico , Aspirina/farmacologia , Aspirina/uso terapêutico , Dabigatrana/farmacologia , Dabigatrana/uso terapêutico , Feminino , Fibrinolíticos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Rivaroxabana/farmacologia , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Vitamina K/antagonistas & inibidores
14.
Br J Clin Pharmacol ; 83(8): 1844-1859, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28205318

RESUMO

AIMS: Nonvitamin K antagonist oral anticoagulants (NOACs) are now available for the prevention of stroke in patients with atrial fibrillation (AF) as an alternative to vitamin K antagonists (VKA) and aspirin. The comparative effectiveness and safety in daily practice of these different drug classes is still unclear. The objective of this study was to evaluate the risk of major bleeding and stroke in AF patients using NOACs, VKAs or aspirin. METHODS: A retrospective cohort study was conducted among AF patients using the UK Clinical Practice Research Datalink (March 2008-October 2014). New users of VKAs, NOACs and low dose aspirin were followed from the date of first prescription of an antithrombotic drug until the occurrence of stroke or major bleeding. Analyses were adjusted for a history of comorbidities and drug use with Cox regression analysis. RESULTS: A total of 31 497 patients were eligible for the study. The hazard ratio (HR) of major bleeding was 2.07 [95% confidence interval (CI) 1.27-3.38] for NOACs compared with VKAs, which was mainly attributed by the increased risk of gastrointestinal bleeding (HR 2.63, 95% CI 1.50-4.62). This increased bleeding risk was restricted to women (HR 3.14, 95% CI 1.76-5.60). Aspirin showed a similar bleeding risk as VKAs. NOACs showed equal effectiveness as VKA in preventing ischaemic stroke (HR 1.22, 95% CI 0.67-2.19). VKAs were more effective than aspirin (HR 2.18, 95% CI 1.83-2.59). CONCLUSIONS: NOACs were associated with a higher risk on gastrointestinal bleeding, particularly in women. The use of NOACs in patients who are vulnerable for this type of bleeding should be carefully considered. NOACs and VKAs are equally effective in preventing stroke. Aspirin was not effective in the prevention of stroke in AF.


Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Hemorragia Gastrointestinal/epidemiologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Vitamina K/antagonistas & inibidores , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Feminino , Seguimentos , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento , Adulto Jovem
15.
BMJ ; 354: i3625, 2016 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-27413017

RESUMO

OBJECTIVE:  To determine the association between use of sulphonylureas and risk of hypoglycaemia in relation to renal function and sulphonylurea metabolic group compared with use of metformin. DESIGN:  Population based cohort study using routinely collected data from general practices in England. SETTING:  Clinical Practice Research Datalink (CPRD) database, 2004-12. PARTICIPANTS:  120 803 new users of a non-insulin antidiabetic agent with at least one prescription and aged 18 years or more. The first prescription defined start of follow-up. Patients were followed until the end of data collection, a record for hypoglycaemia, or a blood glucose level of less than 3.0 mmol/L. MAIN OUTCOME MEASURES:  Associations between sulphonylurea dose, renal impairment, type of sulphonylurea used, and risk of hypoglycaemia, were determined using Cox proportional hazard models. Adjustments were made for age, sex, lifestyle, comorbidity, and drug use. RESULTS:  The risk of hypoglycaemia in current users of sulphonylureas only was significantly increased compared with current users of metformin only (adjusted hazard ratio 2.50, 95% confidence interval 2.23 to 2.82). The higher risk in current users of sulphonylureas only was further increased in patients with an estimated glomerular filtration rate of less than 30 mL/min/1.73 m(2) (4.96, 3.76 to 6.55). The risk of hypoglycaemia was also significantly higher in patients with a high sulphonylurea dose (3.12, 2.68 to 3.62) and in current users of glibenclamide (7.48, 4.89 to 11.44). Gliclazide, the sulphonylurea of first choice, showed a similar risk of hypoglycaemia compared with other sulphonylureas. CONCLUSIONS:  Sulphonylurea treatment in patients with a renal function of less than 30 mL/min/1.73 m(2) should be considered with caution. Moreover, an increased risk of hypoglycaemic events was observed among all users of sulphonylureas. This contrasts with several guidelines that recommend gliclazide as first choice sulphonylurea, and therefore requires further investigation.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Metformina/efeitos adversos , Compostos de Sulfonilureia/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/epidemiologia , Inglaterra/epidemiologia , Feminino , Humanos , Hipoglicemiantes , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Compostos de Sulfonilureia/administração & dosagem , Adulto Jovem
18.
Pharmacoepidemiol Drug Saf ; 24(10): 1017-25, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26183226

RESUMO

INTRODUCTION: Dipeptidyl peptidase-4 inhibitors (DPP4-Is) are a new class of anti-hyperglycemic drugs which might have a potential beneficial effect on bone metabolism. Data on the effect of DPP4-I use and fracture risk is limited and conflicting. The aim of the present study was to investigate the association between use of DPP4-Is and fracture risk. METHODS: A case-control study was conducted using data from the Danish National Health Service. Cases were those who sustained a fracture, and controls were those without a fracture during the study period (2007-2011), all aged 18 years and older. Conditional logistic regression estimated the odds ratios of fracture with current use of DPP4-I use. Analyses were adjusted for comorbidities and recent drug use. RESULTS: Among the cases there were 6993 current non-insulin anti-diabetic drug (NIAD) users (excluding incretin users) and 643 DPP4-I users. There were 7209 NIAD users (excluding incretin users) among the controls and 707 DPP4-I users. Current DPP4-I use was not associated with risk of any fracture (adjusted [adj.] OR: 0.97, 95% CI: 0.79-1.18) or major osteoporotic fracture (adj. OR: 0.96, 95% CI: 0.72-1.28). Stratification of current DPP4-I use to cumulative and average daily dose did not show an association. CONCLUSIONS: In a population-based case-control study we identified that short-term use of DPP4-I was not associated with fracture risk as compared to users of other anti-hyperglycemic drugs. Additionally, results suggest that increasing daily dose and cumulative DPP4-I exposure were not associated with fracture risk. However, more research is needed to assess the effect of long-term DPP4-I use on the risk of fracture.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Fraturas Ósseas/epidemiologia , Hipoglicemiantes/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Fatores de Confusão (Epidemiologia) , Dinamarca/epidemiologia , Diabetes Mellitus/epidemiologia , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Fraturas Ósseas/etiologia , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Risco , Fatores de Tempo , Adulto Jovem
19.
Calcif Tissue Int ; 97(5): 506-15, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26184119

RESUMO

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a new class of drugs that might have a potential beneficial effect on bone metabolism. Data on the effect of GLP-1 RAs and fracture risk are lacking. The aim of the present study was to investigate the association between the use of GLP-1 and the risk of fracture. A case-control study was performed using Danish National Health Service data. Cases were those who sustained a fracture and controls were those without a fracture during the study period (2007-2011), all aged 18 years and above. Conditional logistic regression estimated the odds ratios (OR) of fracture with current use of DPP4-I use. Analyses were adjusted for comorbidities and recent drug use. Among cases (n = 229,114), there were 6993 current non-insulin anti-diabetic drug (NIAD) users (excluding incretin users) and 255 GLP-1 RA users. Similarly, among controls (n = 229,114), 7209 were NIAD users (excluding incretin users) and 220 were GLP-1 RA users. Current GLP-1 RA use was not associated with a decreased risk of fracture [adjusted (adj.) OR 1.16; 95% CI 0.83-1.63]. Osteoporotic fracture risk was also not associated with current GLP-1 RA use (adj. OR 0.78; 95% CI 0.44-1.39). In our nation-wide case-control study, we identified that the use of GLP-1 RA was not associated with fracture risk as compared to the use of other anti-hyperglycemic drugs. Additionally, current GLP-1 RA use, stratified by cumulative or average daily dose, is not associated with fracture risk. Further research should focus on long-term use of GLP-1 RA and fracture risk.


Assuntos
Fraturas Ósseas/epidemiologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Fraturas Ósseas/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
20.
CMAJ Open ; 3(1): E91-6, 2015 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25844376

RESUMO

BACKGROUND: Bisphosphonates are the first-line therapy for the treatment of osteoporosis. In the province of Ontario, the Ontario Drug Benefit Program funds medications for patients aged 65 years and older. The Ontario Drug Benefit Program has a generic substitution policy that requires lower-cost generic drugs to be dispensed when they are available. However, there is controversy surrounding the efficacy and tolerability of generic bisphosphonates. The objective of this study was to describe patterns in the use of brand-name versus generic formulations when dispensing oral bisphosphonate over a 13-year period. METHODS: We identified all osteoporotic preparations for alendronate and risedronate that were dispensed through the Ontario Drug Benefit Program from 2001 to 2014. We stratified our sample into community-dwelling residents and residents in long-term care facilities. The number of prescriptions dispensed per month were plotted to illustrate trends over time. RESULTS: We found a rapid switch from brand-name to generic bisphosphonate equivalents immediately after the generic became available on the Ontario Drug Benefit formulary, with generics accounting for > 88% of dispensed drug within 2 months. We also observed a reduction in the number of generic drugs dispensed each time a new brand-name alternative (e.g., monthly risedronate, weekly alendronate plus vitamin D) was introduced to the formulary. The dispensing trends were similar in the community and long-term care settings. INTERPRETATION: The Ontario Drug Benefit Program generic substitution policy resulted in rapid uptake of generic oral bisphosphonates among seniors in Ontario. However, there was a switch away from generic medications to new brand-name alternatives whenever they were introduced to the formulary. Therefore, some patients continued to use brand-name bisphosphonate despite the availability of generic options.

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