Treatment patterns of antidepressants in children and adolescents in Scandinavia.

The aim of this study was to examine variations in use of antidepressants among children and adolescents in the three Scandinavian countries (Sweden, Norway, and Denmark). We identified new users of antidepressants (5-17 years) during 2007-2018 and described the annual incidence rate, treatment duration, concomitant psychotropic drug use, and the clinical setting of the prescribing physician (in Sweden and Denmark). Incident use of antidepressants increased by a factor 1.9 in Sweden, 1.3 in Norway and decreased by a factor 0.6 in Denmark during the study period. In Sweden, 58% of antidepressant users were covered by a prescription 12 months after initiation compared to 40% in Norway and 49% in Denmark. Also, 34% of Swedish antidepressant users were in continuous treatment after 12 months compared to 26% in Norway and 31% in Denmark. Concomitant use of other psychotropics was more common in Sweden (57%) than in Norway (37%) and Denmark (27%). During 2007-2018, clinicians from psychiatry settings initiated 75% of antidepressant treatments in Sweden, while this was the case for 50% of prescriptions in Denmark, although the proportion increased over time. The number of new antidepressant users is high and still rising in Sweden compared to Norway and Denmark. Swedish antidepressant users are more likely to use other psychotropics and to be covered by an antidepressant prescription after one year. Most antidepressants in Sweden are prescribed by physicians within psychiatric settings suggesting that they are based on specialized psychiatric evaluation.

Validation of Obstetric Diagnosis and Procedure Codes in the Danish National Patient Registry in 2017.

Purpose: This study aimed to systematically evaluate the validity of variables related to pregnancy, delivery, and key characteristics of the infant in the Danish National Patient Register using maternal medical records as the reference standard. Patients and Methods: We reviewed medical records of 1264 women giving birth in the Region of Southern Denmark during 2017. We calculated positive (PPV) and negative (NPV) predictive values, sensitivity, and specificity to estimate the validity of 49 selected variables. Results: The PPV was ≥0.90 on most pregnancy-related variables including parity, pre-gestational BMI, diabetes disorders, and previous cesarean section, while it was lower for hypertensive disorders, especially mild to moderate preeclampsia (0.49, 95% CI 0.32-0.66). Sensitivity ranged from 0.80 to 1.00 on all pregnancy-related variables, except hypertensive disorders (sensitivity 0.38-0.71, lowest for severe preeclampsia). On most delivery-related variables including obstetric surgical procedures (eg cesarean section and induction of labor), pharmacological pain-relief, and gestational age at delivery, PPV's ranged from 0.98 to 1.00 and the corresponding sensitivities from 0.87 to 1.00. Regarding infant-related variables, both the APGAR score registered five minutes after delivery and birthweight yielded a PPV of 1.00. Conclusion: Obstetric coding in the Danish National Patient Register shows very high validity and completeness making it a valuable source for epidemiologic research.

Use of molnupiravir: A Danish nationwide drug utilization study.

PURPOSE: To describe utilization patterns, characteristics of users and prescribers of the new oral antiviral medication, molnupiravir, indicated for mild-to-moderate COVID-19. METHODS: Using nationwide registries, we identified all Danish adults who filled a prescription for molnupiravir from December 16th, 2021, to August 31st, 2022. We described weekly incidence rates and patient characteristics over time, prescriber characteristics as well as time between molnupiravir initiation and a positive SARs-CoV-2 test. Patient characteristics were compared to matched, untreated SARS-CoV-2 positive reference groups. RESULTS: By August 31st, 2022, 5847 individuals had filled a prescription for molnupiravir. The incidence rate gradually increased to 16 weekly prescriptions per 1000 RT-PCR SARS-CoV-2 positives. Users of molnupiravir were most often men (55% vs. 45% women). The majority (81%) had a positive RT-PCR SARS-CoV-2 test and few (2.9%) redeemed molnupiravir outside the recommended window of 5 days from the positive test result. Compared to matched, untreated SARS-CoV-2 positive reference groups, users of molnupiravir had a median age of 74 years versus 49 years, a higher proportion resided in a nursing home (12% vs. 1.5%) and had a higher number of comorbidities (median of 3 vs. 0); most commonly hypertension (38%), chronic lung disease (35%), diabetes (20%) and mood disorders (20%). General practitioners were the primary prescribers of molnupiravir (91%). CONCLUSIONS: Molnupiravir was mainly prescribed by general practitioners to RT-PCR SARS-CoV-2 positive individuals who had a potentially increased risk of severe COVID-19. Though some off-label prescribing occurred, our study indicates a high level of adherence to contemporary guidelines.

Valsartan, Losartan and Irbesartan use in the USA, UK, Canada and Denmark after the nitrosamine recalls: a descriptive cohort study.

OBJECTIVES: To examine valsartan, losartan and irbesartan usage and switching patterns in the USA, UK, Canada and Denmark before and after July 2018, when the first Angiotensin-Receptor-Blocker (ARB) (valsartan) was recalled. DESIGN: Retrospective cohort study. SETTING: USA, Canadian administrative healthcare data, Danish National Prescription Registry and UK primary care electronic health records. PARTICIPANTS: Patients aged 18 years and older between January 2014 and December 2020. INTERVENTION: Valsartan, losartan and irbesartan. MAIN OUTCOME: Monthly percentages of individual ARB episodes, new users and switches to another ARB, ACE inhibitors (ACEI) or calcium channel blockers containing products. RESULTS: We identified 10.8, 3.2, 1.8 and 1.2 million ARB users in the USA, UK, Canada and Denmark, respectively. Overall proportions of valsartan, losartan and irbesartan use were 18.4%, 67.9% and 5.2% in the USA; 3.1%, 48.3% and 10.2% in the UK, 16.3%, 11.4% and 18.3% in Canada, 1%, 93.5% and 0.6% in Denmark. In July 2018, we observed an immediate steep decline in the proportion of valsartan use in the USA and Canada. A similar trend was observed in Denmark; however, the decline was only minimal. We observed no change in trends of ARB use in the UK. Accompanying the valsartan decline was an increase in switching to other ARBs in the USA, Canada and Denmark. There was a small increase in switching to ACEI relative to the valsartan-to-other-ARBs switch. We also observed increased switching from other affected ARBs, losartan and irbesartan, to other ARBs throughout 2019, in the USA and Canada, although the usage trends in the USA remained unchanged. CONCLUSION: The first recall notice for valsartan resulted in substantial decline in usage due to increased switching to other ARBs. Subsequent notices for losartan and irbesartan were also associated with increased switching around the time of the recall, however, overall usage trends remained unchanged.

Methodology of the brodalumab assessment of hazards: a multicentre observational safety (BRAHMS) study.

INTRODUCTION: Safe and effective pharmacological treatment is of paramount importance for treating severe psoriasis. Brodalumab, a monoclonal antibody against interleukin (IL) 17 receptor A, was granted marketing authorisation in the EU in 2017. The European Medicines Agency requested a postauthorisation safety study of brodalumab to address potential safety issues raised during drug development regarding major adverse cardiovascular events, suicidal conduct, cancer and serious infections. METHODS AND ANALYSIS: BRodalumab Assessment of Hazards: A Multinational Safety is a multicentre observational safety study of brodalumab running from 2017 to 2029 using population-based healthcare databases from Denmark, Sweden, Norway, Netherlands, Germany and three different centres in Italy. A distributed database network approach is used, such that only aggregate data are exchanged between sites.Two types of designs are used: a case-time-control design to study acute effects of transient treatment and a variation of the new user active comparator design to study the effects of transient or chronic treatment. As comparators, inhibitors of TNF-α, inhibitors of IL-12 and IL-23, and other inhibitors of cytokine IL-17A are included.In the self-controlled case-time-control design, the risk of developing the outcome of interest during periods of brodalumab use is compared within individuals to the risk in periods without use.In the active comparator cohort design, new users of brodalumab are identified and matched to new users of active comparators. Potential baseline confounders are adjusted for by using propensity score modelling. For outcomes that potentially require large cumulative exposure, an adapted active comparator design has been developed. ETHICS AND DISSEMINATION: The study is approved by relevant authorities in Denmark, Norway, Sweden, the Netherlands, Germany and Italy in line with the relevant legislation at each site. Data confidentiality is secured by the distributed network approach. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EUPAS30280.

Psychotropic Medication Use and Psychiatric Disorders During the COVID-19 Pandemic Among Danish Children, Adolescents, and Young Adults.

Importance: The direct and indirect implications of the COVID-19 pandemic have been associated with the mental health of children and adolescents, but it is uncertain whether these implications have been associated with changes in prescribing and diagnosis patterns. Objective: To examine psychotropic medication use and rates of psychiatric disorders in Danish children, adolescents, and young adults during the COVID-19 pandemic. Design, Setting, and Participants: This population-based, descriptive register-based cohort study included all Danish individuals aged 5 to 24 years from January 1, 2017, until June 30, 2022. Main Outcomes and Measures: Rates of filled prescriptions of psychotropic medications, including antipsychotics, anxiolytics, hypnotics, sedatives, antidepressants, and psychostimulants, and all inpatient and outpatient contacts with mental and behavioral disorders. Rates of new (incident) and total (prevalent) psychotropic medication use and psychiatric diagnoses were estimated. Rate ratios (RRs) were assessed between observed and expected numbers of incident psychotropic medication use or psychiatric diagnoses from March 2020 to June 30, 2022, comparing observed numbers with expected numbers predicted from the modeled prepandemic trend. Results: The study identified 108 840 (58 856 female individuals [54%]; median [IQR] age, 18 [14-22] years) incident psychotropic medication users. From March 2020 (first national lockdown) to June 2022, the rate of incident users of any psychotropic medication showed a relative increase of 18% (RR, 1.18; CI, 1.17-1.20) compared with expected numbers, which was primarily associated with an increase among those aged 12 to 17 years of 37% (RR, 1.37; 95% CI, 1.34-1.41). Similarly, there was an overall relative increase of incident psychiatric disorders of 5% (incidence rate, 1.05; CI, 1.04-1.07) (incident cases, 114 048 [58 708 female individuals (51%)]), which was associated with an increase in hyperkinetic disorders (RR, 1.13; CI, 1.09-1.18) and anxiety disorders (RR, 1.04; CI, 1.02-1.06). Prevalence patterns showed similar trends of an overall increase in psychotropic medication use and psychiatric disorders. One of 3 new users of an individual drug group had filled a prescription for a drug from another psychotropic medication group within the prior 6 months. Conclusions and Relevance: The results of this cohort study suggest that Danish youths experienced an increase in rates of psychotropic treatment and psychiatric disorder diagnoses during the COVID-19 pandemic, which was most pronounced among those aged 12 to 17 years. The increase was observed for children and adolescents with and without a psychiatric history within the last 5 years.

Development and Validation of a Nordic Multimorbidity Index Based on Hospital Diagnoses and Filled Prescriptions.

Purpose: To develop the Nordic Multimorbidity Index (NMI), a multimorbidity measure specifically suited to the Nordic health and administrative registry data based on current diagnosis, treatment, and coding practices. Methods: The NMI was developed to predict 5-year mortality in a population-based cohort of randomly sampled Danish residents aged ≥40 years (n = 425,087) followed from 2013 to 2018. Included predictors were selected from hospital diagnoses and filled drug prescriptions based on a combination of subject matter knowledge and a data-driven approach using backwards elimination. The performance of the NMI was assessed in a temporal validation cohort of Danish residents followed from 2007 to 2012 and in six cohorts of new users of selected drugs. The discriminative performance of the NMI, Charlson Comorbidity Index (CCI) and the Elixhauser Comorbidity Index (ECI) was assessed using the c-statistic from logistic regression models with 5-year mortality as dependent variable and the multimorbidity index score, age, and sex as independent variables. Results: The NMI included 50 predictors. In the temporal validation cohort, the c-statistic of the NMI (0.887, 95% CI 0.883-0.890) exceeded that of the CCI (0.871, 95% CI 0.868-0.874) and ECI (0.866, 95% CI 0.863-0.870). In all new user cohorts, the NMI outperformed the other indices with c-statistics ranging from 0.781 (95% CI 0.779-0.784) to 0.838 (95% CI 0.834-0.842). Conclusion: The NMI predicted 5-year mortality in a general Danish population and six cohorts of new users of selected drugs and was superior to the CCI and ECI. The NMI could be preferred over these indices to quantify the level of multimorbidity for, eg, descriptive purposes or confounding control. The NMI should be validated in other patient populations and other Nordic countries.

Use of hypnotic drugs among children, adolescents, and young adults in Scandinavia.

BACKGROUND: Hypnotic use in children and adolescents is controversial. OBJECTIVE: To describe the use of hypnotic drugs (melatonin, z-drugs, and sedating antihistamines) among 5- to 24-year-old Scandinavians during 2012 to 2018. METHODS: Aggregate-level data were obtained from public data sources in Sweden, Norway, and Denmark. We calculated annual prevalence (users/1000 inhabitants) stratified by age group, sex, and country. Quantity of use (Defined Daily Dose (DDD)/user/day) was estimated for Norway and Denmark. RESULTS: Melatonin was the most commonly used hypnotic, and its use increased markedly from 2012 to 2018, particularly among females and 15- to 24-year-old individuals. Sweden had the highest increase in use (6.5 to 25/1000) compared with Norway (10-20/1000) and Denmark (5.7-12/1000). The annual prevalence of sedating antihistamine use was also highest in Sweden, reaching 13/1000 in 2018 in comparison to 7.5/1000 in Norway and 2.5/1000 in Denmark. Z-drug use decreased in all countries toward 2018, dropping to 3.5/1000 in Sweden, 4.4/1000 in Norway, and 1.7/1000 in Denmark. The quantity of hypnotic use in Norway and Denmark was 0.8-1.0 DDD/user/day for melatonin in 2018, as compared to 0.1-0.3 for z-drugs and antihistamines. CONCLUSION: The use of melatonin and sedating antihistamines increased among young Scandinavians during 2012-2018, and the increase was twice as high in Sweden compared with Norway and Denmark. In addition, Sweden had the highest use of sedating antihistamines. The Scandinavian variation of hypnotic use could reflect differences in frequency of sleep problems between populations or variation of healthcare access or clinical practice between countries.

Validity of Antineoplastic Procedure Codes in the Danish National Patient Registry: The Case of Colorectal Cancer.

BACKGROUND: Procedure codes in the Danish National Patient Registry are used for administrative purposes and are a potentially valuable resource for epidemiologic research. To our knowledge, the validity of antineoplastic procedure codes has only been evaluated in one study. METHODS: We randomly extracted a sample of 420 patients in the Southern Region of Denmark with a diagnosis of colorectal cancer and an oncology contact during 2016-2018. Using the medical record as gold standard, we computed the positive predictive value (PPV) and sensitivity of antineoplastic procedure codes recorded in the Danish National Patient Registry. RESULTS: We identified 2,243 codes for antineoplastic treatments in the registry and 2,299 in the medical records. We confirmed that 213 of 214 patients with registered therapies in the Danish National Patient Registry received therapy, corresponding to a PPV of "any registration" of 1.00 (95% confidence interval [CI] = 0.97, 1.00). Considering single registrations, the overall PPV was 0.95 (95% CI = 0.94, 0.95), and the overall sensitivity was 0.90 (95% CI = 0.89, 0.91). Number of recorded treatments and treatments administered were strongly correlated. Considering the most frequent single antineoplastic regimens, PPV ranged from 0.90 (95% CI = 0.87, 0.92) for capecitabine to 0.98 (95% CI = 0.95, 1.00) for cetuximab, whereas sensitivity ranged from 0.81 (95% CI = 0.75, 0.87) for 5-fluorouracil and irinotecan (FOLFIRI) regimen to 0.97 (95% CI = 0.94, 0.99) for bevacizumab. Analysis per hospital showed the highest validity of registrations at the University Hospital. CONCLUSION: The validity of antineoplastic procedure codes in the Danish National Patient Registry is generally high and thus usable for epidemiologic research.

Caesarean Delivery and Risk of Chronic Inflammatory Diseases (Inflammatory Bowel Disease, Rheumatoid Arthritis, Coeliac Disease, and Diabetes Mellitus): A Population Based Registry Study of 2,699,479 Births in Denmark During 1973-2016.

BACKGROUND: Chronic inflammatory diseases in childhood and early adult life share aetiological factors operating from birth and onwards. In this study, we use data from the national Danish health registers to evaluate the risk of developing four common, immune-mediated hospital-diagnosed childhood chronic inflammatory diseases. METHODS: A national population-based registry study. Data from the Danish Medical Birth Registry and the Danish National Patient Registry from January 1973 to March 2016 were linked at a personal level to evaluate any potential associations between caesarean section and development of Inflammatory bowel diseases, rheumatoid arthritis, coeliac disease and diabetes mellitus among the offspring. A model adjusted for parental age at birth, decade of birth, gender of child, and parents' chronic inflammatory disease status was used. RESULTS: This register-based national cohort study of 2672708 children with information on delivery mode found an increased risk of diabetes, arthritis, coeliac disease, and inflammatory bowel disease for both girls and boys after caesarean section compared with vaginal delivery. The higher risk was present at least 40 years after delivery. In a subgroup analysis, both acute and elective caesarean section was associated with an increased risk of developing a chronic inflammatory disease. CONCLUSIONS: Being born by caesarean section leads to increased host susceptibility for chronic inflammatory diseases that last for decades. This finding should be further addressed in future studies with the aim to support the development of new strategies for prevention, treatment, and maybe even cure.

Ischemic Stroke and Systemic Embolism in Warfarin Users With Atrial Fibrillation or Heart Valve Replacement Exposed to Dicloxacillin or Flucloxacillin.

The antibiotics dicloxacillin and flucloxacillin induce cytochrome P450-dependent metabolism of warfarin. We explored the influence of these drug-drug interactions on the clinical effectiveness of warfarin therapy due to atrial fibrillation or heart valve replacement. Using the population-based Danish registers, we performed a propensity-score matched cohort study including around 50,000 episodes of dicloxacillin/flucloxacillin matched to phenoxymethylpenicillin and to no antibiotic, respectively. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) by comparing 21-day (days 7-28) risks of ischemic stroke/systemic embolism (SE) following initiation of each exposure. When compared with phenoxymethylpenicillin, dicloxacillin/flucloxacillin was associated with an HR of ischemic stroke/SE of 2.09 (95% CI 1.51-2.90; strongest for dicloxacillin (HR 2.17; 95% CI 1.56-3.02)). Use of an untreated comparator strengthened the association (HR 2.84; 95% CI 1.97-4.09). Dicloxacillin should be used with caution in patients receiving warfarin. This may also apply to flucloxacillin; however, more data on the risks associated with flucloxacillin exposure during warfarin therapy are needed.

Linking glycemic dysregulation in diabetes to symptoms, comorbidities, and genetics through EHR data mining.

Diabetes is a diverse and complex disease, with considerable variation in phenotypic manifestation and severity. This variation hampers the study of etiological differences and reduces the statistical power of analyses of associations to genetics, treatment outcomes, and complications. We address these issues through deep, fine-grained phenotypic stratification of a diabetes cohort. Text mining the electronic health records of 14,017 patients, we matched two controlled vocabularies (ICD-10 and a custom vocabulary developed at the clinical center Steno Diabetes Center Copenhagen) to clinical narratives spanning a 19 year period. The two matched vocabularies comprise over 20,000 medical terms describing symptoms, other diagnoses, and lifestyle factors. The cohort is genetically homogeneous (Caucasian diabetes patients from Denmark) so the resulting stratification is not driven by ethnic differences, but rather by inherently dissimilar progression patterns and lifestyle related risk factors. Using unsupervised Markov clustering, we defined 71 clusters of at least 50 individuals within the diabetes spectrum. The clusters display both distinct and shared longitudinal glycemic dysregulation patterns, temporal co-occurrences of comorbidities, and associations to single nucleotide polymorphisms in or near genes relevant for diabetes comorbidities.

Social inequality in diabetes patients' morbidity patterns from diagnosis to death - A Danish register-based investigation.

AIM: Measuring socioeconomic inequalities in health and health care, and understanding determinants of such inequalities, are critical for achieving higher equity in health. Equity in health is a prerequisite for public health and welfare. The aim of the paper is (1) to quantify inequality in diabetes morbidity patterns over patients' entire life span, and (2) to compare levels of inequality measured through income and educational level, respectively, as proxies for socioeconomic status (SES). METHOD: Historic individual register data on the entire Danish diabetes population alive in 2011 were gathered. Cox survival analysis and a concentration index decomposition approach were applied to analyse relevant morbidity indicators reflecting patients' health state at diagnosis and throughout their lives with diabetes. RESULTS: Patients with high education have approximately 26% lower mortality hazard when diagnosed with diabetes and 10-15% lower hazard of developing complications as compared with patients with short education. The outcome variables: 'severe complications at diagnosis' and 'years with severe complications' inhibit the highest negative concentration index value, indicating that morbidity is concentrated among the lower SES groups, whereas the outcome variables 'years without complications' and 'duration of diabetes' concentrate among the socioeconomically better-off patients. CONCLUSIONS: Significant differences in diabetes patients' morbidity patterns and survival indicate that diabetes impacts harder on patients of lower SES; these patients experience more severe complications and die earlier. Hence to reduce inequality in health, it is important to invest in efforts targeted towards socially vulnerable groups.

Socioeconomic inequality of diabetes patients' health care utilization in Denmark.

Understanding socioeconomic inequalities in health care is critical for achieving health equity. The aim of this paper is threefold: 1) to quantify inequality in diabetes health care service utilization; 2) to understand determinants of these inequalities in relation to socio-demographic and clinical morbidity factors; and 3) to compare the empirical outcome of using income level and educational level as proxies for Socio Economic Status (SES).Data on the entire Danish population of diabetes patients in 2011 (N = 318,729) were applied. Patients' unique personal identification number enabled individual patient data from several national registers to be linked. A concentration index approach with decomposition into contributing factors was applied. Differences in diabetes patients' health care utilization patterns suggest that use of services differ among patients of lower and higher SES, despite the Danish universal health care system. Especially, out-patient services, rehabilitation and specialists in primary care show different utilization patterns according to SES. Comparison of the empirical outcome from using educational level and income level as proxy for patients' SES indicate important differences in inequality estimates. While income, alike other measures of labor market attachment, to a certain extent is explained by morbidity and thus endogenous, education is more decisive for patients' ability to take advantage of the more specialized services provided in a universal health care system.

Cancer of unknown primary: Registered procedures compared with national integrated cancer pathway for illuminating external validity.

Cancer of unknown primary (CUP) ranges within top 10 cancers in both incidence and mortality. As primary identification is crucial to choosing treatment, guidelines on CUP emphasize the diagnostic strategy. Whether guidelines are complied with, or if they are indeed helpful, is however unclear. We compared procedures performed in suspected CUP patients with recommendations of national guidelines to assess external validity of guidelines.The Danish National Patient Registry (NPR) comprising population data was utilized to identify the suspected CUP patients during 2009 to 2010 and explore exposure to procedures and patient survival. The cohort was investigated in terms of validity of diagnosis through cross-referencing with the Cancer Registry (CR), which served as gold standard for cancer diagnoses and patients' cancer histories.The NPR cohort consisted of 542 patients (275 males, 264 females) of whom 210 (38.7%) had a CUP diagnosis confirmed. Within the cohort, 347 patients (64.0%) had a registration in CR matching with the NPR registration. Exposure to diagnostic procedures included biopsy (n = 439, 81.0%) and image modalities (n = 532, 98.2%). Survival was poor with 67 (12.4%) individuals alive after 4 years.The validity of a CUP diagnosis in NPR was low when using data from CR as reference. More than half the suspected CUP patients had a previous cancer diagnosis with CUP being the most frequent. Patients were diagnosed in compliance with guidelines indicating high external validity, but less than 1 quarter had their primary identified and the 1-year survival was approximately 20%. Research is needed to develop efficacious methods for primary detection.

Incidence, morbidity, mortality, and prevalence of diabetes in Denmark, 2000-2011: results from the Diabetes Impact Study 2013.

PURPOSE: As part of the Danish Diabetes Impact Study 2013, we present trends in the incidence, morbidity, mortality, and prevalence of diabetes in Denmark for the period 2000 through 2011. PATIENTS AND METHODS: The Danish National Diabetes Register was established in 2006 and is assumed to cover all patients with diabetes, alive as of the end of 1996, and all subsequent new cases. The present study is based on the content of the register as of July 3, 2013 (n=497,232 patients). Using the personal identification code assigned to all Danish inhabitants, all available supplementary information from the Danish National Patient Register and the Danish Civil Registration Service was used to define the date of diagnosis of diabetes and the first date of experiencing complications (grouped according to impact and severity). RESULTS: During the period of 2000 to 2011, the incidence rate of diabetes increased approximately 5% annually. During the same period, decreasing trends were observed for both the rates of progression in complications and of the complication-specific mortality. During the same period, the prevalence of diabetes doubled. CONCLUSION: The increasing prevalence of diabetes in Denmark is driven by increasing incidence combined with decreasing morbidity and mortality in the population of patients with diabetes. These mechanisms will be explored further as part of the Diabetes Impact Study 2013, together with investigations into the socioeconomic and health economic aspects of diabetes.

Identification of possible adverse drug reactions in clinical notes: The case of glucose-lowering medicines.

OBJECTIVE: Through manual review of clinical notes for patients with type 2 diabetes mellitus attending a Danish diabetes center, the aim of the study was to identify adverse drug reactions (ADRs) associated with three classes of glucose-lowering medicines: "Combinations of oral blood-glucose lowering medicines" (A10BD), "dipeptidyl peptidase-4 (DDP-4) inhibitors" (A10BH), and "other blood glucose lowering medicines" (A10BX). Specifically, we aimed to describe the potential of clinical notes to identify new ADRs and to evaluate if sufficient information can be obtained for causality assessment. METHODS: For observed adverse events (AEs) we extracted time to onset, outcome, and suspected medicine(s). AEs were assessed according to World Health Organization-Uppsala Monitoring Centre causality criteria and analyzed with respect to suspected medicines, type of ADR (system organ class), seriousness and labeling status. FINDINGS: A total of 207 patients were included in the study leading to the identification of 163 AEs. 14% were categorized as certain, 60% as probable/likely, and 26% as possible. 15 (9%) ADRs were unlabeled of which two were serious: peripheral edema associated with sitagliptin and stomach ulcer associated with liraglutide. Of the unlabeled ADRs, 13 (87%) were associated with "other blood glucose lowering medications," the remaining 2 (13%) with "DDP-4 inhibitors." CONCLUSION: Clinical notes could potentially reveal unlabeled ADRs associated with prescribed medicines and sufficient information is generally available for causality assessment. However, manual review of clinical notes is too time-consuming for routine use and hence there is a need for developing information technology (IT) tools for automatic screening of patient records with the purpose to detect information about potentially serious and unlabeled ADRs.

Mining of hospital laboratory information systems: a model study defining age- and gender-specific reference intervals and trajectories for plasma creatinine in a pediatric population.

BACKGROUND: The knowledge of physiological fluctuation and variation of even commonly used biochemical quantities in extreme age groups and during development is sparse. This challenges the clinical interpretation and utility of laboratory tests in these age groups. To explore the utility of hospital laboratory data as a source of information, we analyzed enzymatic plasma creatinine as a model analyte in two large pediatric hospital samples. METHODS: Plasma creatinine measurements from 9700 children aged 0-18 years were obtained from hospital laboratory databases and partitioned into high-resolution gender- and age-groups. Normal probability plots were used to deduce parameters of the normal distributions from healthy creatinine values in the mixed hospital datasets. Furthermore, temporal trajectories were generated from repeated measurements to examine developmental patterns in periods of changing creatinine levels. RESULTS: Creatinine shows great age dependence from birth throughout childhood. We computed and replicated 95% reference intervals in narrow gender and age bins and showed them to be comparable to those determined in healthy population studies. We identified pronounced transitions in creatinine levels at different time points after birth and around the early teens, which challenges the establishment and usefulness of reference intervals in those age groups. CONCLUSIONS: The study documents that hospital laboratory data may inform on the developmental aspects of creatinine, on periods with pronounced heterogeneity and valid reference intervals. Furthermore, part of the heterogeneity in creatinine distribution is likely due to differences in biological and chronological age of children and should be considered when using age-specific reference intervals.

Validation of the danish national diabetes register.

The Danish National Diabetes Register (NDR) was established in 2006 and builds on data from Danish health registers. We validated the content of NDR, using full information from the Danish National Patient Register and data from the literature. Our study indicates that the completeness in NDR is ≥95% concerning ascertainment from data sources specific for diabetes, ie, prescriptions with antidiabetic drugs and diagnoses of diabetes in the National Patient Register. Since the NDR algorithm ignores diabetes-related hospital contacts terminated before 1990, the establishment of the date of inclusion is systematically delayed for ≥10% of the registrants in general and for ≥30% of the inclusions before 1997 in particular. This bias is enhanced for ascertainment by chiropody services and by frequent measurements of blood glucose because the date of reimbursement of services, rather than the date of encounter, has been taken as the date of inclusion in NDR. We also find that some 20% of the registrations in NDR may represent false positive inclusions of persons with frequent measurements of blood glucose without having diabetes. We conclude that NDR is a novel initiative to support research in the epidemiological and public health aspects of diabetes in Denmark, but we also present a list of recommended changes for improving validity, by reducing the impact of current sources of bias and misclassifications.