Danish National Hospital Discharge Register Research Articles

Multimorbidity clusters potentially superior to individual diseases for stratifying fracture risk in older people: a nationwide cohort study.

Comorbidities are common in fracture patients, but the interaction between fracture and comorbidities remains unclear. This study aimed to define specific multimorbidity clusters in older adults and quantify the association between the multimorbidity clusters and fracture risk. This nationwide cohort study includes 1.7 million adults in Denmark aged ≥50years who were followed from 2001 through 2014 for an incident low-trauma fracture. Chronic diseases and fractures were identified from the Danish National Hospital Discharge Register. Latent class analysis and Cox's regression were conducted to define the clusters and quantify fracture risk, respectively. The study included 793815 men (age: 64 ± 10) and 873524 women (65.5 ± 11), with a third having ≥1 chronic disease. The pre-existent chronic diseases grouped individuals into low-multimorbidity (80.3% in men, 83.6% in women), cardiovascular (12.5%, 10.6%), malignant (4.1%, 3.8%), diabetic (2.4%, 2.0%) and hepatic clusters (0.7%, men only). These clusters distinguished individuals with advanced, complex, or late-stage disease from those having earlier-stage disease. During a median follow-up of 14years (IQR: 6.5, 14), 95372 men and 212498 women sustained an incident fracture. The presence of multimorbidity was associated with a significantly greater risk of fracture, independent of age and sex. Importantly, the multimorbidity clusters had the highest discriminative performance in assessing fracture risk, whereas the strength of their association with fracture risk equalled or exceeded that of both the individual chronic diseases most prevalent in each cluster and of counts-based comorbidity indices. Future fracture prevention strategies should take comorbidities into account. Multimorbidity clusters may provide greater insight into fracture risk than individual diseases or counts-based comorbidity indices.

'Skeletal Age' for mapping the impact of fracture on mortality.

Fragility fracture is associated with an increased risk of mortality, but mortality is not part of doctor-patient communication. Here, we introduce a new concept called 'Skeletal Age' as the age of an individual's skeleton resulting from a fragility fracture to convey the combined risk of fracture and fracture-associated mortality for an individual. We used the Danish National Hospital Discharge Register which includes the whole-country data of 1,667,339 adults in Denmark born on or before January 1, 1950, who were followed up to December 31, 2016 for incident low-trauma fracture and mortality. Skeletal age is defined as the sum of chronological age and the number of years of life lost (YLL) associated with a fracture. Cox's proportional hazards model was employed to determine the hazard of mortality associated with a specific fracture for a given risk profile, and the hazard was then transformed into YLL using the Gompertz law of mortality. During the median follow-up period of 16 years, there had been 307,870 fractures and 122,744 post-fracture deaths. A fracture was associated with between 1 and 7 years of life lost, with the loss being greater in men than women. Hip fractures incurred the greatest loss of life years. For instance, a 60-year-old individual with a hip fracture is estimated to have a skeletal age of 66 for men and 65 for women. Skeletal Age was estimated for each age and fracture site stratified by gender. We propose 'Skeletal Age' as a new metric to assess the impact of a fragility fracture on an individual's life expectancy. This approach will enhance doctor-patient risk communication about the risks associated with osteoporosis. National Health and Medical Research Council in Australia and Amgen Competitive Grant Program 2019.

Association of Multimorbidity and Excess Mortality After Fractures Among Danish Adults

Limited knowledge about interactions among health disorders impedes optimal patient care. Because comorbidities are common among patients 50 years and older with fractures, these fractures provide a useful setting for studying interactions among disorders. To define multimorbidity clusters at the time of fracture and quantify the interaction between multimorbidity and fracture in association with postfracture excess mortality. This nationwide cohort study included 307 870 adults in Denmark born on or before January 1, 1951, who had an incident low-trauma fracture between January 1, 2001, and December 31, 2014, and were followed up through December 31, 2016. Data were analyzed from February 1 to March 31, 2022. Fracture and 32 predefined chronic diseases recorded within 5 years before the index fracture were identified from the Danish National Hospital Discharge Register. Death was ascertained from the Danish Register on Causes of Death. Latent class analysis was conducted to identify multimorbidity clusters. Relative survival analysis was used to quantify excess mortality associated with the combination of multimorbidity and fractures at specific sites. Among the 307 870 participants identified with incident fractures, 95 372 were men (31.0%; mean [SD] age at fracture, 72.3 [11.2] years) and 212 498 were women (69.0%; mean [SD] age at fracture, 74.9 [11.2] years). During a median of 6.5 (IQR, 3.0-11.0) years of follow-up, 41 017 men (43.0%) and 81 727 women (38.5%) died. Almost half of patients with fractures (42.9%) had at least 2 comorbidities. Comorbidities at fracture were categorized as low-multimorbidity (60.5% in men and 66.5% in women), cardiovascular (23.7% in men and 23.5% in women), diabetic (5.6% in men and 5.0% in women), malignant (5.1% in men and 5.0% in women), and mixed hepatic and/or inflammatory (5.1% in men only) clusters. These clusters distinguished individuals with advanced, complex, or late-stage disease from those with earlier-stage disease. Multimorbidity and proximal or lower leg fractures were associated with increased mortality risk, with the highest excess mortality found in patients with hip fracture in the malignant cluster (1-year excess mortality: 40.8% [95% CI: 38.1%-43.6%]). The combination of multimorbidity and fracture compounded the association with mortality, conferring much greater risk than either alone. Concomitant illnesses were common and clustered into distinct multimorbidity clusters that were associated with excess postfracture mortality. The compound contribution of multimorbidity to postfracture excess mortality highlights the need for more comprehensive approaches in these high-risk patients. The analytical approach applied to fracture could also be used to examine other sentinel health events.

A greater awareness of children with glucose-6-phosphate dehydrogenase deficiency is imperative in western countries.

This national retrospective Danish study described the characteristics of children diagnosed with glucose-6-phosphate dehydrogenase (G6PD) deficiency, an inherited X-linked recessive disorder that often affects children of Middle Eastern descent. We studied children born between 1 January 2000 and 31 December 2017 and diagnosed with G6PD deficiency. They were identified from the Danish National Hospital Discharge Register and the Danish Database of Extreme Neonatal Hyperbilirubinaemia. There were 113 children diagnosed with G6PD deficiency, 67% were of Middle Eastern descent and they were frequently diagnosed before the onset of symptoms, based on known heredity. Of the 67 infants born in Denmark, 10% had extreme neonatal hyperbilirubinaemia and one developed kernicterus spectrum disorder, as did one child born in the Middle East. Most (61%) of the 33 children with jaundice received phototherapy, 12% had exchange transfusions and 18% received whole blood transfusions. After the neonatal period, 23% of the cohort had blood transfusions and 4% needed intensive care for acute haemolytic anaemia. The incidence of G6PD deficiency appeared to be severely underestimated. Many families from countries where G6PD deficiency is endemic move to Denmark and other Western countries. Greater awareness is essential to avoid chronic and potentially lethal, consequences.

The epidemiology of fractures in Denmark in 2011.

SummaryIn the present study, we used national health care databases to estimate fracture incidence rates (IRs) and compared these IRs based on imputed data. We showed that imputation could lead to both over- and underestimation of IRs, and future research should therefore focus on how to improve those imputations.IntroductionOsteoporosis is a major public health burden through associated (osteoporotic) fractures. In Denmark, the incidence rates (IRs) of hip fracture are widely available. However, there is limited data about other fracture sites. A recent report could only provide imputed IRs, although nationwide data is readily available in electronic healthcare databases. Therefore, our aim was to estimate fracture site-specific IRs for Denmark in 2011 and to compare those to the previously reported imputed data.MethodsData from the Danish National Hospital Discharge Register was used to estimate age- and gender-specific IRs for any fracture as well as for different fracture sites in the Danish population aged 20 years and older in 2011. Hip fracture IRs were stratified to sub-sites, and IRs were determined for all hip fractures which were confirmed by surgery.ResultsThe total number of incident fractures in 2011 was 80,760 (IR 191, 95 % confidence interval (CI) 190–192 (per 10,000 person-years)), of which 35,398 (43.8 %, IR 171, 95 % CI 169–173) occurred in men and 45,362 (56.2 %, IR 211, 95 % CI 209–213) in women. The majority of the fractures occurred in the population aged 50 years and older (n = 50,470, IR 249, 95 % CI 247–251). The numbers of any hip fracture were lower than the previously imputed estimates, whereas the number of forearm fractures was higher.ConclusionWe showed age- and gender-specific fracture rates for any fracture as well as for different fracture sites. The IRs of most fracture sites increased with age. Estimating the number of fractures for Denmark based on imputation of data from other countries led to both over- and underestimation. Future research should therefore focus on how to improve those imputations as not all countries have nationwide registry data.

Use of Antiepileptic Drugs During Pregnancy and Risk of Spontaneous Abortion and Stillbirth

Objective To determine whether use of antiepileptic drugs during pregnancy may increase the risk of spontaneous abortion or stillbirth. Design Population based cohort study. Setting Register based study in Denmark, 1997-2008. Participants 983 305 pregnancies identified in the Danish medical birth register and the Danish national hospital discharge register from 1 February 1997 to 31 December 2008 were linked to the Danish Register of Medicinal Product Statistics to obtain information on use of antiepileptic drugs. Main outcome measures Risk ratio of spontaneous abortion and stillbirth after use of antiepileptic drugs during pregnancy, estimated by using binomial regression adjusting for potential confounders of maternal age, cohabitation, income, education, history of severe mental disorder, and history of drug misuse. Results Antiepileptic drugs were used in a total of 4700 (0.5%) pregnancies. 16 out of 100 pregnant women using antiepileptics and 13 out of 100 pregnant women not using antiepileptics experienced a spontaneous abortion. After adjusting for potential confounders pregnant women using antiepileptics had a 13% higher risk of spontaneous abortions than pregnant women not using antiepileptics (adjusted risk ratio 1.13, 95% confidence interval 1.04 to 1.24). However, the risk of spontaneous abortion was not increased in women with an epilepsy diagnosis (0.98, 0.87 to 1.09), only in women without a diagnosis of epilepsy (1.30, 1.14 to 1.49). In an analysis including women with at least two pregnancies with discordant antiepileptic drug use (for example, use in the first pregnancy but not in the second), the adjusted hazard ratio for spontaneous abortion was 0.83 (0.69 to 1.00) for exposed pregnancies compared with unexposed pregnancies. Stillbirth was identified in 18 women who used antiepileptic drugs (unadjusted risk ratio 1.29, 0.80 to 2.10). Conclusion Among women with epilepsy and when analysing the risk in antiepileptic drug discordant pregnancies in the same woman, we found no overall association between the use of antiepileptic drugs during pregnancy and spontaneous abortions. Therefore unmeasured confounding may explain the slight increased risk for spontaneous abortion with any antiepileptic drug use (among women both with and without epilepsy). We found no association between antiepileptic drug use during pregnancy and stillbirth, but the statistical precision was low.

Predictors of mortality subsequent to a fracture in diabetes mellitus patients.

Type-1 and type-2 diabetes mellitus (DM) are associated with an increased fracture risk and possibly an increased risk of death following a fracture. To investigate the association between diabetes-related drugs and mortality following a fracture. A nested case-control study was conducted. Cases were patients with DM who died following a fracture; controls were DM patients not dying after a fracture. We identified DM patients using the Danish National Hospital Discharge Register (1977-2011) and included information on date of DM diagnosis, date of fracture, and comorbidities. From the Danish Cause of Death Register, the date of death was collected (2008-2011). From the Central Region of Jutland, Denmark, medication use was collected (2008-2011). Analysis was performed by unconditional logistic regression. Two thousand six hundred twenty one diabetes patients with a fracture following the diabetes diagnosis and with information on medication use were included. Of these, 229 died. In a multivariate analysis, statin use [n = 1,106 (42%) statin users, odds ratio (OR) = 0.60, 95% confidence interval, p = 0.012] decreased the risk of dying subsequent to a fracture. Male gender (OR = 1.57, p = 0.005), increasing age (OR = 1.08, p < 0.001), a diagnosis of retinopathy (OR = 2.12, p = 0.008), heart failure (OR = 1.68, p = 0.004), and use of glucocorticoids (OR = 2.22, p = 0.001) were associated with an increased risk of death. None of the antidiabetics: biguanides, glucagon-like receptor agonists, β-cell stimulants, glitazones, and insulin were associated with mortality. Co-morbidity reflected by late onset complications, heart failure, and glucocorticoid use was associated with an increased risk of mortality subsequent to a fracture. Statin use may reduce mortality subsequent to a fracture in diabetes patients. Clinical trials are needed to determine whether diabetes patients with a fracture should initiate statin treatment.

Risk of cardiovascular disease: The effects of diabetes and anti-diabetic drugs — A nested case–control study

AimsType 2 diabetes (DM) increases the risk of cardiovascular disease. We investigated the effects of antidiabetic drugs on the composite endpoint (CE) of ischemic heart disease, heart failure or stroke in DM patients. MethodsWe conducted a nested case–control study. Cases were DM patients who subsequently suffered from CE; controls were DM patients with no history of CE after DM diagnosis. Using the Danish National Hospital Discharge Register, we included DM patients with information on date of DM diagnosis, date of CE, and comorbidities. From the Central Region of Jutland, Denmark, medication use and biochemical parameters were collected. Logistic regression analyses were conducted and mutually adjusted for comorbidities, pharmaceutical use, and biochemical parameters. Results10,073 DM patients were included (65,550person-years). 1947 suffered from a subsequent CE. CE prior to DM diagnosis (OR=20.18, 95% CI: 16.88–24.12), neuropathy (OR=1.39, 95% CI: 1.05–1.85) and peripheral artery disease (OR=1.31, 95% CI: 1.02–1.69) increased the risk of CE. Biguanides (OR=0.62 95% CI; 0.54–0.71) and liraglutide (OR=0.48 95% CI; 0.38–0.62) significantly decreased the risk of CE as did statin treatment (OR=0.63, 95% CI: 0.54–0.72). DPP-4 inhibitors, insulin and β-cell stimulating agents had neutral effect. When results were adjusted for biochemical risk markers (1103 patients, 7271person-years, 189 cases), biguanides (OR=0.54, 95% CI: 0.34–0.87) and liraglutide (OR=0.32, 95% CI: 0.14–0.70) treatment retained a significant risk reduction. The effect of liraglutide was dose and duration dependent (p<0.05). ConclusionWe have shown an association between the use of biguanides and liraglutide and a reduced risk of CE in DM patients.

Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth: population based cohort study

Objective To determine whether use of antiepileptic drugs during pregnancy may increase the risk of spontaneous abortion or stillbirth. Design Population based cohort study. Setting Register based study in Denmark,...

Sibship structure and risk of infectious mononucleosis: a population-based cohort study.

Present understanding of increased risk of Epstein-Barr virus (EBV)-related infectious mononucleosis among children of low birth order or small sibships is mainly based on old and indirect evidence. Societal changes and methodological limitations of previous studies call for new data. We used data from the Danish Civil Registration System and the Danish National Hospital Discharge Register to study incidence rates of inpatient hospitalizations for infectious mononucleosis before the age of 20 years in a cohort of 2,543,225 Danes born between 1971 and 2008, taking individual sibship structure into account. A total of 12,872 cases of infectious mononucleosis were observed during 35.3 million person-years of follow-up. Statistical modelling showed that increasing sibship size was associated with a reduced risk of infectious mononucleosis and that younger siblings conferred more protection from infectious mononucleosis than older siblings. In addition to this general association with younger and older siblings, children aged less than 4 years transiently increased their siblings’ infectious mononucleosis risk. Our results were confirmed in an independent sample of blood donors followed up retrospectively for self-reported infectious mononucleosis. Younger siblings, and to a lesser degree older siblings, seem to be important in the transmission of EBV within families. Apparently the dogma of low birth order in a sibship as being at the highest risk of infectious mononucleosis is no longer valid.

Pregnancy outcomes in women with primary hyperparathyroidism.

To study pregnancy and pregnancy outcomes in women with primary hyperparathyroidism (PHPT) and in controls. Register-based retrospective cohort study of women aged 16-44 years with a diagnosis of PHPT with age- and gender-matched non-exposed controls in Denmark. The patients and controls were identified using the Danish National Hospital Discharge Register for the period 1977-2010. The outcomes were determined using the Birth Register, the Abortion Register and the LPR (National Hospital Discharge Register). The primary outcome was the relative risk of abortions in patients compared with controls. A total of 1057 women with PHPT and 3171 controls were identified. The number of women giving birth and experiencing abortions did not differ between the two groups (live births, P=0.21 and abortions, P=0.12). Also birth weight, length, Apgar score, and gestation length at abortion did not differ. Within the first year after the diagnosis was made, gestation length was lower in women with PHPT than that in controls. However, this was linked to more deliveries by caesarian sections. A diagnosis of PHPT did not seem to increase the rate of abortions in our study. Reducing the abortion risk may therefore not be an indication for parathyroidectomy during pregnancy in patients with mild PHPT. The PHPT diagnosis does not seem to affect birth weight, length and Apgar score. The higher number of deliveries by cesarean section after the diagnosis was made may be associated with lower gestation age. The strategy for delivery should be carefully considered in pregnant women with PHPT.

A Genetic Basis for Infectious Mononucleosis: Evidence From a Family Study of Hospitalized Cases in Denmark

Circumstantial evidence from genome-wide association and family studies of various Epstein-Barr virus-associated diseases suggests a substantial genetic component in infectious mononucleosis (IM) etiology. However, familial aggregation of IM has scarcely been studied. We used data from the Danish Civil Registration System and the Danish National Hospital Discharge Register to study rate ratios of IM in a cohort of 2 823 583 Danish children born between 1971 and 2011. Specifically, we investigated the risk of IM in twins and in first-, second-, and third-degree relatives of patients with IM. In the analyses, IM was defined as a diagnosis of IM in a hospital contact. Effects of contagion between family members were dealt with by excluding follow-up time the first year after the occurrence of IM in a relative. A total of 16 870 cases of IM were observed during 40.4 million person-years of follow-up from 1977 to 2011. The rate ratios and the associated 95% confidence intervals were 9.3 (3.0-29) in same-sex twins, 3.0 (2.6-3.5) in siblings, 1.9 (1.6-2.2) in children, 1.4 (1.3-1.6) in second-degree relatives, and 1.0 (0.9-1.2) in third-degree relatives of IM patients. The rate ratios were very similar for IM in children (aged 0-6 years) and older children/adolescents (aged 7-19 years). We found evidence of familial aggregation of IM that warrants genome-wide association studies on IM disease etiology, especially to examine commonalities with causal pathways in other Epstein-Barr virus-related diseases.

Liraglutide and Insulin are Associated with a Decreased Risk of Acute Myocardial Infarction in Type 2 Diabetes Mellitus Patients

Objective: Type 2 Diabetes Mellitus (DM) is associated with an increased risk of cardiovascular events. Glycemic control is beneficial to reduce acute myocardial infarction (AMI), however little is known whether a specific antidiabetic treatment is superior to another. This study aims at examining antidiabetic drugs and their association with a subsequent AMI in patients with DM. Methods: A nested case-control study was conducted. Cases were patients with DM who subsequently suffered from AMI; controls were DM patients with no subsequent AMI after DM diagnosis. Using the Danish National Hospital Discharge Register, we included DM patients with information on date of DM diagnosis, date of AMI, and comorbidities. From the Central Region of Jutland, Denmark, medication use and biochemical parameters were collected. Multivariate logistic regression analyses were conducted. Results: 10,727 DM patients were included. In multivariate analysis liraglutide (OR= 0.386, 95%CI 0.218-0.682) decreased the risk of AMI. An AMI prior to DM diagnosis (OR=36.004, 95%CI: 24.441-53.038), increasing age (1.027, 95%CI 1.016-1.039), increasing diabetes duration (1.060, 95%CI 1.043-1.077), male gender (OR=1.310, 95%CI 1.025-1.676), a diagnosis of heart failure (OR=2.083, 95%CI: 1.459-2.973), and peripheral artery disease (OR=1.506, 95%CI: 1.032-2.198) were all significantly associated with the risk of subsequent AMI. Neither insulin, β- cell stimulans, biguanides, antihypertensive treatment nor usage of statins or antiarrhythmic drugs showed any significance. When additional adjustment by biochemical risk markers was done insulin was significantly associated with a reduced risk of AMI (OR=0.235, 95%CI 0.073-0.757). .Furthermore, liraglutide and biguanides both showed a significant dose- and exposure time effects on OR for AMI. Conclusion: We have found a strong association between the use of liraglutide and insulin, and a reduced risk of AMI in patients with DM when taking general risk factors into account.

Mapping the prescriptiome to fractures in men—a national analysis of prescription history and fracture risk

A nationwide case-control study was performed in 62,865 men aged 50+ using fracture data from the national hospital discharge register to screen all redeemed prescriptions in the past 5 years for significant mapping to fracture risk, employing measures to control for false discovery rate. Osteoporosis in men is frequently related to alcohol abuse, hypogonadism, hypercalciuria, or the use of glucocorticoids. Very limited information is available on the impact of other medications on fracture risk in men. We conducted a nationwide population-based case-control study collecting fracture data from the Danish National Hospital Discharge Register and prescriptions from the National Prescriptions Database (1995-2000). We included men aged 50+ years, with hospital-treated fractures in the year 2000 (n = 15,716), and age- and sex-matched controls (n = 47,149). We identified 3.2 million redemptions of prescriptions for 1,073 different drugs. The analysis confirmed associations between fracture risk and use of sedatives, anti-epileptics, anti-psychotics, anxiolytics, SSRI, opioids and other analgesics, loop diuretics, and glucorticoids. New associations were also found. We observed an odds ratio (OR [95% CI] for any fracture) for fracture in users of dopaminergic agents (1.6 [1.3-1.9]) and iron compounds (1.2 [1.1-1.5]). The largest impact on fracture risk at population level was exerted by loop diuretics and analgesics. An array of drugs is associated with fracture risk in men. The "prescriptiome" analysis can be used as a surveillance tool for drug-induced osteoporosis and in the planning of preventive measures.

Fracture risk in Danish men with prostate cancer: a nationwide register study

To assess the risk of fracture attributable to prostate cancer, and the impact of exposure to prescribed gonadotrophin-releasing hormone agonists and antiandrogens on this risk in a nationwide, population-based case-control study. Data from the Danish National Hospital Discharge Register, the National Bureau of Statistics, and the National Prescriptions Database were merged. The analysis covered 15 716 men aged >50 years presenting with a fracture at any hospital in Denmark in 2000, and 47 149 age-matched control men. A previous diagnosis of prostate cancer had been recorded in 1.3% of controls and 2.5% of those with a fracture. Prostate cancer was associated with an increased odds ratio (95% confidence interval) for all fractures of 1.8 (1.6-2.1), for hip fractures of 3.7 (3.1-4.4), but no increased risk of vertebral fractures. The increased fracture risk became apparent early after diagnosis and remained pronounced even in long-term survivors. Androgen deprivation therapy (ADT) with an odds ratio of 1.7 (1.2-2.5; P < 0.01) and orchidectomy, at 1.7 (1.2-2.4; P < 0.01) added to the overall fracture risk. In all, 3.1% of hip fractures in Danish men aged >50 years are attributable to prostate cancer. Prostate cancer, orchidectomy and the use of ADT are associated with a markedly greater risk of fractures, especially of the hip. The risk of hip fracture is not confined to the very old, neither is the risk made negligible by the excess mortality in patients with advanced prostate cancer.

Are fractures due to anticoagulants or the disease necessitating the treatment?

Assessing potential adverse effects of drugs is not an easy task. Iyisoy et al. raises relevant methodological questions and advise clinician to be cautious on using data from non-randomised trials in clinical practice. Unfortunately, randomised controlled trails (RCT) performed prior to the acceptance of new drugs do not always reveal all adverse effects [ [1] Stricker B.H. Psaty B.M. Detection, verification, and quantification of adverse drug reactions. BMJ. 2004; 329: 44-47 Crossref PubMed Scopus (154) Google Scholar ]. Moreover, post-marketing's RCT are not always an option due to ethical concerns. A good example is whether treatment with vitamin K antagonists (VKA) increases the risk of fracture. Due to the well-documented beneficial effect of VKA in e.g. atrial fibrillation (AFLI), it is not an option to randomise patients with AFLI to treatment with either VKA or placebo. Neither is it feasible to randomise healthy subjects in order to study potential harmful effects. Thus, other methodological approaches are needed. In our pharmaco-epidemiological study, we took advantages of the uniformly organized Danish health care system [ [2] Rejnmark L. Vestergaard P. Mosekilde L. Fracture risk in users of oral anticoagulants: A nationwide case–control study. Int J Cardiol. 2007; 118: 338-344 Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar ]. In Denmark, it is not possible to redeem a prescription for a drug, without registration in the national prescription database. Moreover, the Danish National Hospital Discharge Register covers all contacts (on in- or out-patient basis) to the hospitals with an almost 100% completeness of recordings and a high precision of diagnoses, especially of fracture diagnoses [ [3] Vestergaard P. Mosekilde L. Fracture risk in patients with celiac Disease, Crohn's disease, and ulcerative colitis: a nationwide follow-up study of 16,416 patients in Denmark. Am. J. Epidemiol. 2002; 156: 1-10 Crossref PubMed Scopus (273) Google Scholar ]. Using these registers it is possible to identify, with an almost 100% certainty, all patients who have sustained a fracture (cases), as well as subject who have not fractured (controls). As Denmark has a Civil Registration System, which has electronic records on all citizens it is possible to make a valid link between these registers. Iyisoy et al. state that our study is a “retrospective” case–control study. It is true, that case–control studies by design are retrospective, meaning that they are comparing previous risk factors between cases and controls. They may therefore typically be at risk of i.e. recall bias. However, all data have been registered prospectively in our study i.e., data on exposure and confounders were collected before the date of hospitalization for fracture. Therefore, recall bias did not influence data collection. However, all study designs have drawbacks e.g., our analysis may be influenced by potential confounding factors not included in the analyses.

Seasonal variation in hospital discharge diagnosis of atrial fibrillation: a population-based study.

Cardiovascular events such as acute myocardial infarction and stroke vary seasonally, with a peak incidence during the winter and a trough during the summer. Few data exist on the seasonal variation of atrial fibrillation. We examined the association among season, outdoor temperature, and risk of atrial fibrillation. We identified 32,992 subjects, age 50-89 years, in a random sample of half the people with an incident hospital discharge diagnosis of atrial fibrillation in the Danish National Hospital Discharge Register from 1980 to 1993. We used a periodic regression model to evaluate any seasonal distribution. We found a winter peak and a summer trough in the incidence of atrial fibrillation. The relative incidence of atrial fibrillation during winter as compared with summer, estimated as the ratio of the incidence in the month of the peak relative to the incidence in the month of the trough, was small (relative risk = 1.20; 95% confidence interval = 1.12-1.29). Stratification by sex, age, and the presence or absence of diabetes and underlying cardiovascular diseases did not affect the seasonal pattern. We also found an inverse relation between mean outdoor temperature and incidence of atrial fibrillation. The risk of atrial fibrillation was modestly higher during the winter and was inversely associated with outdoor temperature.

Clinical trends in atrial fibrillation at the turn of the millenium

Clinical trends in atrial fibrillation at the turn of the millenium

Incident thromboembolism in the aorta and the renal, mesenteric, pelvic, and extremity arteries after discharge from the hospital with a diagnosis of atrial fibrillation.

The impact of atrial fibrillation (AF) on risk of peripheral arterial thromboembolism is unknown. We analyzed the risk of thromboembolism (embolus and/or thrombosis) in the aorta and the renal, mesenteric, pelvic, and extremity arteries in a cohort of patients discharged from the hospital with an incident diagnosis of AF relative to the risk of thromboembolism in these vessels in the Danish population. In a random sample of half of the Danish population, 14 917 men and 14 945 women aged 50 to 89 years were identified in the Danish National Hospital Discharge Register with a diagnosis of AF from January 1, 1980, through December 31, 1993. Patients were followed up from diagnosis of AF in the Danish National Hospital Discharge Register and the Causes of Death Register until the first diagnosis of a thromboembolic event, death, or the end of 1993. Risk of a thromboembolic event relative to the risk in the Danish population was analyzed by means of Poisson regression modeling. Patients with a hospital diagnosis of AF had an increased risk of thromboembolic events in the aorta and the renal, mesenteric, pelvic, and extremity arteries (relative risk, 4.0 [95% confidence interval, 3.5-4.6] in men; and relative risk, 5.7 [95% confidence interval, 5.1-6.3] in women) compared with the Danish population. A hospital diagnosis of AF is an important risk factor for peripheral arterial thromboembolic complications.

Decrease in mortality in patients with a hospital diagnosis of atrial fibrillation in Denmark during the period 1980-1993.

Atrial fibrillation is associated with increased mortality. We hypothesized that the death rate in atrial fibrillation patients in Denmark has diminished during the period 1980-1993. In a random sample of half of the Danish population, 30 330 patients were found to have a diagnosis of incident atrial fibrillation in the Danish National Hospital Discharge Register 1980-1993. Information on previous and concomitant cardiovascular and metabolic diseases during the period 1977-1993 was sought in the register. The temporal trend in total and cardiovascular mortality in the cohort of atrial fibrillation patients was analysed. A significant decrease in total and cardiovascular mortality was seen, 12-13% for total mortality and 17-18% for cardiovascular mortality. By adjusting for the decreasing cardiovascular mortality rate in the general population, a decrease in the relative risk of total mortality of 8-13% with time was seen for the atrial fibrillation cohort, compared with the population risk, while no reduction in the relative risk of cardiovascular death was seen. A significant decrease in mortality with calendar period occurred in the cohort of atrial fibrillation patients.