Lars Hougaard Nielsen

IT University of Copenhagen, København, Capital Region, Denmark

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Publications (15)84.39 Total impact

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    O. Lidegaard · L.H. Nielsen · C.W. Skovlund
    Journal of Vascular Surgery 10/2012; 56(4):1181. DOI:10.1016/j.jvs.2012.08.056 · 2.98 Impact Factor
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    ABSTRACT: AimsThe benefit of extending clopidogrel treatment beyond the 12-month period recommended in current guidelines after myocardial infarction (MI) is debated. We analysed the risk of adverse cardiovascular outcomes after discontinuation of 12 months of clopidogrel treatment.Methods and resultsThis Danish retrospective nationwide study included all patients treated with clopidogrel after discharge from a first-time MI during 2004-09. The risk of death or recurrent MI after the discontinuation of clopidogrel was studied by multivariable Poisson regression models. Patients treated with and without percutaneous coronary intervention (PCI) were analysed separately. The follow-up was 18 months. Of the 29 268 patients included, 3214 (11.0) experienced death or recurrent MI. There were 9819 (33.6) patients treated only medically and 19 449 (66.4) patients treated with PCI. Twelve months after the index MI, for patients treated only medically, the risk of death or recurrent MI in the first 90-day period of clopidogrel discontinuation was 1.07 (0.65-1.76; P 0.79) [adjusted incidence rate ratio (IRR) and 95 confidence interval] compared with the next 90-day period of discontinuation. For patients treated with PCI, the corresponding IRR was 1.59 (1.11-2.30; P 0.013). The risk of recurrent MI yielded an IRR of 0.77 (0.36-1.67; P 0.51) for patients treated only medically and 1.87 (1.11-3.15; P 0.019) for PCI-treated patients.Conclusion Discontinuation of clopidogrel 12 months after MI is associated with an increased risk of death or recurrent MI in the first 90 days of discontinuation compared with the next 90-day period of discontinuation for patients treated with PCI, but not for patients not treated with PCI.
    European Heart Journal 07/2012; 33(20):2527-34. DOI:10.1093/eurheartj/ehs202 · 14.72 Impact Factor
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    ABSTRACT: To assess the risk of venous thrombosis in current users of non-oral hormonal contraception. Historical national registry based cohort study. Four national registries in Denmark. All Danish non-pregnant women aged 15-49 (n=1,626,158), free of previous thrombotic disease or cancer, were followed from 2001 to 2010. Incidence rate of venous thrombosis in users of transdermal, vaginal, intrauterine, or subcutaneous hormonal contraception, relative risk of venous thrombosis compared with non-users, and rate ratios of venous thrombosis in current users of non-oral products compared with the standard reference oral contraceptive with levonorgestrel and 30-40 µg oestrogen. Diagnoses were confirmed by at least four weeks of anticoagulation therapy after the diagnosis. Within 9,429,128 woman years of observation, 5287 first ever venous thrombosis events were recorded, of which 3434 were confirmed. In non-users of hormonal contraception the incidence rate of confirmed events was 2.1 per 10,000 woman years. Compared with non-users of hormonal contraception, and after adjustment for age, calendar year, and education, the relative risk of confirmed venous thrombosis in users of transdermal combined contraceptive patches was 7.9 (95% confidence interval 3.5 to 17.7) and of the vaginal ring was 6.5 (4.7 to 8.9). The corresponding incidences per 10,000 exposure years were 9.7 and 7.8 events. The relative risk was increased in women who used subcutaneous implants (1.4, 0.6 to 3.4) but not in those who used the levonorgestrel intrauterine system (0.6, 0.4 to 0.8). Compared with users of combined oral contraceptives containing levonorgestrel, the adjusted relative risk of venous thrombosis in users of transdermal patches was 2.3 (1.0 to 5.2) and of the vaginal ring was 1.9 (1.3 to 2.7). Women who use transdermal patches or vaginal rings for contraception have a 7.9 and 6.5 times increased risk of confirmed venous thrombosis compared with non-users of hormonal contraception of the same age, corresponding to 9.7 and 7.8 events per 10,000 exposure years. The risk was slightly increased in women using subcutaneous implants but not in those using the levonorgestrel intrauterine system.
    BMJ (online) 05/2012; 344(may10 3):e2990. DOI:10.1136/bmj.e2990 · 16.38 Impact Factor
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    ABSTRACT: To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose. National historical registry based cohort study. Four registries in Denmark. Non-pregnant Danish women aged 15-49 with no history of thrombotic disease and followed from January 2001 to December 2009. Relative and absolute risks of first time venous thromboembolism. Within 8,010,290 women years of observation, 4307 first ever venous thromboembolic events were recorded and 4246 included, among which 2847 (67%) events were confirmed as certain. Compared with non-users of hormonal contraception, the relative risk of confirmed venous thromboembolism in users of oral contraceptives containing 30-40 µg ethinylestradiol with levonorgestrel was 2.9 (95% confidence interval 2.2 to 3.8), with desogestrel was 6.6 (5.6 to 7.8), with gestodene was 6.2 (5.6 to 7.0), and with drospirenone was 6.4 (5.4 to 7.5). With users of oral contraceptives with levonorgestrel as reference and after adjusting for length of use, the rate ratio of confirmed venous thromboembolism for users of oral contraceptives with desogestrel was 2.2 (1.7 to 3.0), with gestodene was 2.1 (1.6 to 2.8), and with drospirenone was 2.1 (1.6 to 2.8). The risk of confirmed venous thromboembolism was not increased with use of progestogen only pills or hormone releasing intrauterine devices. If oral contraceptives with desogestrel, gestodene, or drospirenone are anticipated to increase the risk of venous thromboembolism sixfold and those with levonorgestrel threefold, and the absolute risk of venous thromboembolism in current users of the former group is on average 10 per 10,000 women years, then 2000 women would need to shift from using oral contraceptives with desogestrel, gestodene, or drospirenone to those with levonorgestrel to prevent one event of venous thromboembolism in one year. After adjustment for length of use, users of oral contraceptives with desogestrel, gestodene, or drospirenone were at least at twice the risk of venous thromboembolism compared with users of oral contraceptives with levonorgestrel.
    BMJ (online) 10/2011; 343:d6423. DOI:10.1136/bmj.d6423 · 16.38 Impact Factor
  • Lars Hougaard Nielsen · Niels Keiding
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    ABSTRACT: Prescription databases are increasingly used in epidemiological studies concerning the use and the effects of drugs. However, this source of data does not provide direct observations of the time of initiation and discontinuation of drug treatment, and these time points therefore need to be estimated. The paper investigates the validity of methods that are used in the literature to identify discontinuation of treatment from prescription data, and we consider the example of post-menopausal hormone therapy. Validation is investigated in terms of a simulation study based on a multistate model for the relationship between episodes of treatment with hormone therapy and occurrence of prescription refills. The multistate model that is introduced is estimated from joint observations of a prescription registry and a cross-sectional survey, involving techniques from the analysis of backward recurrence times. We demonstrate that estimated time points of discontinuation of treatment are highly uncertain, and this may influence studies concerning the immediate effect of discontinuation of treatment. Despite this limitation, we find that a valid assessment of current treatment status (never, current or previous drug use) can be obtained from prescription data. Copyright (c) 2010 Royal Statistical Society.
    Applied Statistics 05/2010; 59(4):707-722. DOI:10.1111/j.1467-9876.2010.00712.x · 1.42 Impact Factor
  • Lise Aagaard · Lars Hougaard Nielsen · Ebba Holme Hansen
    Drug Safety 10/2009; DOI:10.2165/00002018-200932110-1131668 · 2.62 Impact Factor
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    ABSTRACT: Many studies which investigate the effect of drugs categorize the exposure variable into never, current, and previous use of the study drug. When prescription registries are used to make this categorization, the exposure variable possibly gets misclassified since the registries do not carry any information on the time of discontinuation of treatment.In this study, we investigated the amount of misclassification of exposure (never, current, previous use) to hormone therapy (HT) when the exposure variable was based on prescription data. Furthermore, we evaluated the significance of this misclassification for analysing the risk of breast cancer. Prescription data were obtained from Danish Registry of Medicinal Products Statistics and we applied various methods to approximate treatment episodes. We analysed the duration of HT episodes to study the ability to identify discontinuation of therapy from prescription data. Furthermore, we compared to results based on self-reported duration of HT from the Danish Nurse Cohort.Finally, we analysed the effect of HT exposure on time to breast cancer for the different prescription based exposure variables as well as for self-reported HT use. The results of time to discontinuation varied strongly across the different HT assessments. However, misclassification of HT exposure at baseline was limited and hence analysis of the effect of HT on time to breast cancer showed stability across the different exposure assessments with Hazard Ratios ranging from 1.68 to 1.78 for current use compared to never use. The findings suggest that it is possible to estimate the effect of never, current and previous use of HT on breast cancer using prescription data.
    Pharmacoepidemiology and Drug Safety 02/2009; 18(2):147-53. DOI:10.1002/pds.1693 · 3.17 Impact Factor
  • Lise Aagaard · Lars Hougaard Nielsen · Ebba Holme Hansen
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    ABSTRACT: Background: Reporting adverse drug reactions (ADRs) has traditionally been the sole province of healthcare professionals. Since 2003 in Denmark, consumers have been able to report ADRs directly to the authorities. The objective of this study was to compare ADRs reported by consumers with ADRs reported from other sources, in terms of their type, seriousness and the suspected medicines involved. Methods: The number of ADRs reported to the Danish ADR database from 2004 to 2006 was analysed in terms of category of reporter, seriousness, category of ADRs by system organ class (SOC) and the suspected medicines on level 1 of the anatomical therapeutic chemical (ATC) classification system. ADR reports from consumers were compared with reports from other sources (physicians, pharmacists, lawyers, pharmaceutical companies and other healthcare professionals). Chi-square and odds ratios (ORs) were calculated to investigate the dependence between type of reporter and reported ADRs (classified by ATC or SOC). Findings: We analysed 6319 ADR reports corresponding to 15 531 ADRs. Consumers reported 11% of the ADRs. Consumers? share of ?serious? ADRs was comparable to that of physicians (approximately 45%) but lower than that of pharmacists and other healthcare professionals. When consumer reports were compared with reports from other sources, consumers were more likely to report ADRs from the following SOCs: ?nervous system disorders? (OR = 1.27; 95% CI 1.05, 1.53); ?psychiatric disorders? (OR = 1.70; 95% CI 1.31, 2.20) and ?reproductive system and breast disorders? (OR = 2.02; 95% CI 1.13, 3.61) than other sources. Compared with other sources, consumers reported fewer ADRs from the SOCs ?blood and lymphatic system disorders? (OR = 0.22; 95% CI 0.08, 0.59) and ?hepatobiliary system disorders? (OR = 0.14; 95% CI 0.04, 0.57). Consumers were more likely to report ADRs.
    Drug Safety 01/2009; 32(11):1067-74. DOI:10.2165/11316680-000000000-00000 · 2.62 Impact Factor
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    ABSTRACT: There was a discrepancy between data in the Women's Health Initiative (WHI) showing increased risk of coronary artery disease and stroke associated with continuous combined hormone therapy (HT), and prior observational studies suggesting that HT would have a primary preventive effect on cardiovascular disease. A previous study suggested that WHI data and observational results would be more in agreement if time since initiation of HT was controlled. Some investigators believed that the WHI data may not be applicable for healthy younger peri-menopausal women. This population-based observational study evaluated the influence of age, various regimens, routes of administration, duration of use, progestagen types, and estrogen dose on the risk of myocardial infarction (MI) associated with HT. National registry information on 698,098 healthy Danish women, aged 51-69, were followed from 1995 to 2001. Exposure to HT was recorded on a daily basis from a central prescription registry. Relative risk (RR) estimates were analyzed by Poisson regression analysis. A total of 4957 MI events were identified within the 6 year study period. Compared to women who never used HT, current use of hormones did not increase the overall risk of MI (RR, 1.03; 95% confidence interval [CI], 0.95-1.11). Among women in the youngest age group (51-54 years), however, there was an increased risk of MI (adjusted RR, 1.24; 95% CI, 1.02-1.51). The adjusted RR was 0.92 with a 95% CI of 0.80-1.06 in the older age groups. Increased risk of MI was also associated among women in the youngest age group with longer duration of HT (>4 years); this association was not found in the older age groups. The highest risk of MI among all age groups was found with the continuous combined regimen (adjusted RR, 1.35; 95% CI, 1.18-1.53). No significant risk was associated with cyclic combined therapy, unopposed estrogen, or tibolone. The risk associated with the dermal route for unopposed estrogen was significantly lower than for oral delivery (P ≤ .04). No overall indication of increased risk of MI was found with increasing doses of estrogen or progestagen type. These data did not show any overall association between HT and risk of MI among older women who currently used HT; increased risk was found in younger women. Longer duration of HT also increased the risk among younger women, but not older women.
    Obstetrical and Gynecological Survey 12/2008; 64(1):33-35. DOI:10.1097/01.ogx.0000340777.01689.44 · 2.36 Impact Factor
  • L. Aagaard · L. H. Nielsen · E. H. Hansen
    Drug Safety 10/2008; 31(10). DOI:10.2165/00002018-200831100-00189 · 2.62 Impact Factor
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    ABSTRACT: To assess the risk of myocardial infarction (MI) as a result of hormone therapy (HT), with focus on the influence of age, duration of HT, various regimens and routes, progestagen type, and oestrogen dose. All healthy Danish women (n = 698,098, aged 51-69) were followed during 1995-2001. On the basis of a central prescription registry, daily updated national capture on HT was determined. National Registers identified 4947 MI incidents. Poisson regression analyses estimated rate ratios (RRs). Overall, we found no increased risk [RR 1.03 (95% CI: 0.95-1.11)] of MI with the current HT compared with women who never used HT; age-stratified RR among women aged 51-54, 55-59, 60-64, and 65-69 years were 1.24 (1.02-1.51), 0.96 (0.82-1.12), 1.11 (0.97-1.27), and 0.92 (0.80-1.06), respectively. An increasing risk with longer duration was found for younger women, which was not observed with older age groups. In all age groups, the highest risk of MI was found with continuous HT regimen. No increased risk was found with unopposed oestrogen, cyclic combined therapy, or tibolone. Significantly lower risk was found with dermal route than oral unopposed oestrogen therapy (P = 0.04). No associations were found with progestagen type or oestrogen dose. In a National cohort study, we found that HT regimen and route of application could modify the influence of HT on the risk of MI.
    European Heart Journal 10/2008; 29(21):2660-8. DOI:10.1093/eurheartj/ehn408 · 14.72 Impact Factor
  • Astin Bulletin 06/2008; 38(1):137-146. DOI:10.2143/AST.38.1.2030406 · 0.61 Impact Factor
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    Lars Hougaard Nielsen · Ellen Løkkegaard · Anne Helms Andreasen · Niels Keiding
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    ABSTRACT: Pharmacoepidemiological studies often use prescription registries to assess patients' drug episodes. The databases usually provide information on the date of the redemption of the prescription as well as on the dispensed amount, and this allows us to define episodes of drug use. However, when patients take less medication than prescribed, apparent gaps between prescriptions occur, and most studies handle this issue by allowing for small gaps when defining continuous drug use. This paper argues that it becomes crucial whether gaps are 'filled' prospectively or retrospectively. In the latter case the inferred exposure status depends on the patient's future dispensing behaviour and this can lead to severe bias in the findings of the study. In this paper we investigate this potential bias in a study of the risk of acute myocardial infarction (AMI) for women using hormone therapy (HT), and we show that the retrospective exposure definition introduces an artificially protective effect of HT.
    Pharmacoepidemiology and Drug Safety 04/2008; 17(4):384-8. DOI:10.1002/pds.1549 · 3.17 Impact Factor
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    ABSTRACT: We investigate a concept of multivariate pricing, which includes claim history for more than one line of business and is a generalization of the Bühlmann- Straub model. The multivariate credibility model is extended to allow for the age of claims to influence the estimation of future claims. The model is applied to data from a portfolio of commercial lines of business.
    Astin Bulletin 01/2008; 38(1). DOI:10.2139/ssrn.871441 · 0.61 Impact Factor
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    Bent Nielsen · Jens Perch Nielsen · Lars Hougaard Nielsen
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    ABSTRACT: Some times time series experts choose to filter their data before carrying out their final analysis and some times regression experts fit a calendar effect to their data and apply time series techniques afterwards to understand the volatility of their estimated calendar effect. In both these cases only some features of the model have been formally specified. In this paper we introduce a new concept -time series regression. We consider the linear regression case combined with a time series that we formulate as an added latent time series. We give a complete theoretical analyses of this full model and apply it on real data from a business planning problem.