Showing papers in "Clinical Epidemiology in 2015"

The Danish National Patient Registry: a review of content, data quality, and research potential.

Abstract: Background The Danish National Patient Registry (DNPR) is one of the world’s oldest nationwide hospital registries and is used extensively for research. Many studies have validated algorithms for identifying health events in the DNPR, but the reports are fragmented and no overview exists.

Risk factors for amyotrophic lateral sclerosis.

Abstract: Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. It is typically fatal within 2–5 years of symptom onset. The incidence of ALS is largely uniform across most parts of the world, but an increasing ALS incidence during the last decades has been suggested. Although recent genetic studies have substantially improved our understanding of the causes of ALS, especially familial ALS, an important role of non-genetic factors in ALS is recognized and needs further study. In this review, we briefly discuss several major genetic contributors to ALS identified to date, followed by a more focused discussion on the most commonly examined non-genetic risk factors for ALS. We first review factors related to lifestyle choices, including smoking, intake of antioxidants, physical fitness, body mass index, and physical exercise, followed by factors related to occupational and environmental exposures, including electromagnetic fields, metals, pesticides, β-methylamino-L-alanine, and viral infection. Potential links between ALS and other medical conditions, including head trauma, metabolic diseases, cancer, and inflammatory diseases, are also discussed. Finally, we outline several future directions aiming to more efficiently examine the role of non-genetic risk factors in ALS.

Ethical aspects of registry-based research in the Nordic countries

Abstract: National health care registries in the Nordic countries share many attributes, but different legal and ethical frameworks represent a challenge to promoting effective joint research. Internationally, there is a lack of knowledge about how ethical matters are considered in Nordic registry-based research, and a lack of knowledge about how Nordic ethics committees operate and what is needed to obtain an approval. In this paper, we review ethical aspects of registry-based research, the legal framework, the role of ethics review boards in the Nordic countries, and the structure of the ethics application. We discuss the role of informed consent in registry-based research and how to safeguard the integrity of study participants, including vulnerable subjects and children. Our review also provides information on the different government agencies that contribute registry-based data, and a list of the major health registries in Denmark, Finland, Iceland, Norway, and Sweden. Both ethical values and conditions for registry-based research are similar in the Nordic countries. While Denmark, Finland, Iceland, Norway, and Sweden have chosen different legal frameworks, these differences can be resolved through mutual recognition of ethical applications and by harmonizing the different systems, likely leading to increased collaboration and enlarged studies.

Cushing’s syndrome: Epidemiology and developments in disease management

Abstract: Cushing’s syndrome is a rare disorder resulting from prolonged exposure to excess glucocorticoids. Early diagnosis and treatment of Cushing’s syndrome is associated with a decrease in morbidity and mortality. Clinical presentation can be highly variable, and establishing the diagnosis can often be difficult. Surgery (resection of the pituitary or ectopic source of adrenocorticotropic hormone, or unilateral or bilateral adrenalectomy) remains the optimal treatment in all forms of Cushing’s syndrome, but may not always lead to remission. Medical therapy (steroidogenesis inhibitors, agents that decrease adrenocorticotropic hormone levels or glucocorticoid receptor antagonists) and pituitary radiotherapy may be needed as an adjunct. A multidisciplinary approach, long-term follow-up, and treatment modalities customized to each individual are essential for optimal control of hypercortisolemia and management of comorbidities.

The clinical epidemiology of male osteoporosis: a review of the recent literature

Abstract: Osteoporosis, a musculoskeletal disease characterized by decreased bone mineral density (BMD) and an increased risk of fragility fractures, is now recognized as an important public health problem in men. Osteoporotic fractures, particularly of the hip, result in significant morbidity and mortality in men and lead to considerable societal costs. Many national and international organizations now address screening and treatment for men in their osteoporosis clinical guidelines. However, male osteoporosis remains largely underdiagnosed and undertreated. The objective of this paper is to provide an overview of recent findings in male osteoporosis, including pathophysiology, epidemiology, and incidence and burden of fracture, and discuss current knowledge about the evaluation and treatment of osteoporosis in males. In particular, clinical practice guidelines, fracture risk assessment, and evidence of treatment effectiveness in men are addressed.

Using multiple imputation to deal with missing data and attrition in longitudinal studies with repeated measures of patient-reported outcomes.

Abstract: Objective: Missing data is a ubiquitous problem in studies using patient-reported measures, decreasing sample sizes and causing possible bias. In longitudinal studies, special problems relate to attrition and death during follow-up. We describe a methodological approach for the use of multiple imputation (MI) to meet these challenges. Methods: In a cohort of patients treated with percutaneous coronary intervention followed with use of repetitive questionnaires and information from national registers over 3 years, only 417 out of 1,726 patients had complete data on all measure points and covariates. We suggest strategies for use of MI and different methods for dealing with death along with sensitivity analysis of deviations from the assumption of missing at random, all with the use of standard statistical software. The Mental Component Summary from Short Form 12-item survey was used as an example. Conclusion: Ignoring missing data may cause bias of unknown size and direction in longitudinal studies. We have illustrated that MI is a feasible method to try to deal with bias due to missing data in longitudinal studies, including attrition and nonresponse, and should be considered in combination with analysis of sensitivity in longitudinal studies. How to handle dropout due to

Clinical features, epidemiology, and therapy of lymphangioleiomyomatosis

Abstract: Lymphangioleiomyomatosis (LAM) is a multisystem disease of women, characterized by proliferation of abnormal smooth muscle-like LAM cells, leading to the formation of lung cysts, fluid-filled cystic structures in the axial lymphatics (eg, lymphangioleiomyomas), and renal angiomyolipomas. LAM is caused by mutations of the TSC1 or TSC2 genes, which encode, respectively, hamartin and tuberin, two proteins with a major role in control of the mammalian target of rapamycin (mTOR) signaling pathway. LAM occurs sporadically or in association with tuberous sclerosis complex, an autosomal-dominant syndrome characterized by widespread hamartomatous lesions. LAM may present with progressive dyspnea, recurrent pneumothorax, or chylothorax. Pulmonary function tests show reduced flow rates (forced expiratory volume in the first second) and diffusion capacity. Exercise testing may reveal gas exchange abnormalities, ventilatory limitation, and hypoxemia. The severity and progression of disease may be assessed by lung histology scores, quantification of computed tomography, pulmonary function testing, 6-minute walk tests, cardiopulmonary exercise testing, and measurement of serum vascular endothelial growth factor D levels. Sirolimus and everolimus, two mTOR inhibitors, are effective in stabilizing lung function and reducing the size of chylous effusions, lymphangioleiomyo-mas, and angiomyolipomas. However, inhibition of mTOR complex 1 increases autophagy, possibly enhancing LAM cell survival. Inhibition of autophagy with hydroxychloroquine, in combination with sirolimus, has been proposed as a possible treatment for LAM. Deficiency of tuberin results in increased RhoA GTPase activity and cell survival, an effect that is mediated through mTOR complex 2 signaling. Because sirolimus and everolimus only affect the activity of mTOR complex 1, therapies targeting RhoA GTPases with simvastatin, which inhibits Rho GTPases and promotes apoptosis, are being investigated. As in the case of cancer, LAM may be best treated with multiple drugs targeting signaling pathways considered important in the pathogenesis of disease.

Validity of self-reported body mass index among middle-aged participants in the norwegian Women and Cancer study

Abstract: © 2015 Skeie et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

SpineData - a Danish clinical registry of people with chronic back pain.

Abstract: Background Large-scale clinical registries are increasingly recognized as important resources for quality assurance and research to inform clinical decision-making and health policy. We established a clinical registry (SpineData) in a conservative care setting where more than 10,000 new cases of spinal pain are assessed each year. This paper describes the SpineData registry, summarizes the characteristics of its clinical population and data, and signals the availability of these data as a resource for collaborative research projects. Methods The SpineData registry is an Internet-based system that captures patient data electronically at the point of clinical contact. The setting is the government-funded Medical Department of the Spine Centre of Southern Denmark, Hospital Lillebaelt, where patients receive a multidisciplinary assessment of their chronic spinal pain. Results Started in 2011, the database by early 2015 contained information on more than 36,300 baseline episodes of patient care, plus the available 6-month and 12-month follow-up data for these episodes. The baseline questionnaire completion rate has been 93%; 79% of people were presenting with low back pain as their main complaint, 6% with mid-back pain, and 15% with neck pain. Collectively, across the body regions and measurement time points, there are approximately 1,980 patient-related variables in the database across a broad range of biopsychosocial factors. To date, 36 research projects have used data from the SpineData registry, including collaborations with researchers from Denmark, Australia, the United Kingdom, and Brazil. Conclusion We described the aims, development, structure, and content of the SpineData registry, and what is known about any attrition bias and cluster effects in the data. For epidemiology research, these data can be linked, at an individual patient level, to the Danish population-based registries and the national spinal surgery registry. SpineData also has potential for the conduct of cohort multiple randomized controlled trials. Collaborations with other researchers are welcome.

Adaption and validation of the Safety Attitudes Questionnaire for the Danish hospital setting.

Abstract: Purpose: Measuring and developing a safe culture in health care is a focus point in creating highly reliable organizations being successful in avoiding patient safety incidents where these could normally be expected. Questionnaires can be used to capture a snapshot of an employee’s perceptions of patient safety culture. A commonly used instrument to measure safety climate is the Safety Attitudes Questionnaire (SAQ). The purpose of this study was to adapt the SAQ for use in Danish hospitals, assess its construct validity and reliability, and present benchmark data. Materials and methods: The SAQ was translated and adapted for the Danish setting (SAQ-DK). The SAQ-DK was distributed to 1,263 staff members from 31 in- and outpatient units (clinical areas) across five somatic and one psychiatric hospitals through meeting admin istration, hand delivery, and mailing. Construct validity and reliability were tested in a crosssectional study. Goodness-of-fit indices from confirmatory factor analysis were reported along with inter-item correlations, Cronbach’s alpha (α), and item and subscale scores. Results: Participation was 73.2% (N=925) of invited health care workers. Goodness-of-fit indi ces from the confirmatory factor analysis showed: c 2 =1496.76, P,0.001, CFI 0.901, RMSEA (90% CI) 0.053 (0.050-0056), Probability RMSEA (p close)=0.057. Inter-scale correlations between the factors showed moderate-to-high correlations. The scale stress recognition had significant negative correlations with each of the other scales. Questionnaire reliability was high, (α=0.89), and scale reliability ranged from α=0.70 to α=0.86 for the six scales. Proportions of participants with a positive attitude to each of the six SAQ scales did not differ between the somatic and psychiatric health care staff. Substantial variability at the unit level in all six scale mean scores was found within the somatic and the psychiatric samples. Conclusion: SAQ-DK showed good construct validity and internal consistency reliability. SAQ-DK is potentially a useful tool for evaluating perceptions of patient safety culture in

Prevalence of bone metastases and bone-targeting agent use among solid tumor patients in the United States.

Abstract: Purpose Patients with bone metastases are at an increased risk of experiencing morbidity due to bone complications, and bone-targeting agents (BTA) are indicated for the prevention of these complications. Population-based estimates of the prevalence of bone metastases associated with solid tumors, and current treatment patterns for these patients, are limited. This study was undertaken to estimate the prevalence of bone metastases from solid tumors and to describe recent trends in the use of BTA in the US.

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

Abstract: 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.

Statin prescription patterns, adherence, and attainment of cholesterol treatment goals in routine clinical care: a Danish population-based study.

Abstract: Purpose To examine the annual rate and cumulative prevalence of statin use in Denmark 2004-10, including adherence of use and attainment of cholesterol targets. Methods We included all individuals aged 18-86 years with a first statin prescription in Northern Denmark in 2004-10. We calculated the annual rate and cumulative prevalence of statin use. We examined cholesterol values before and after start of statins and the proportion reaching targets according to European guidelines and cardiovascular risk group. Results The study population consisted of 161,646 new statin users (51% men; median age 62 years). The peak rate of new statin initiators occurred in 2008, and a cumulative prevalence of 94 users per 1,000 population was reached in 2010. In total, 98% of new users started with simvastatin. Eighty-eight percent (142,897) did not switch statin type during follow-up. Overall persistence was 84%. The reduction in median total cholesterol in new statin users was 28% (from 6.3 mmol/L to 4.5 mmol/L), while it was 43% (from 4.0 mmol/L to 2.3 mmol/L) for low-density lipoprotein cholesterol. Among patients with very high cardiovascular risk, 66% attained the recommended total cholesterol target; corresponding figures were 74% among high-risk patients and 80% among low- to moderate-risk patients. Corresponding figures for low-density lipoprotein cholesterol were 54%, 82%, and 88%, respectively. Conclusions Statin use has become very prevalent in Danish adults, with high adherence. Cholesterol reduction after statin initiation is similar to that found in clinical trials, yet a substantial proportion of patients does not reach target cholesterol levels.

Adverse pregnancy outcomes after exposure to methylphenidate or atomoxetine during pregnancy.

Abstract: OBJECTIVE To determine if prenatal exposure to methylphenidate (MPH) or atomoxetine (ATX) increases the risk of adverse pregnancy outcomes in women with attention deficit/hyperactivity disorder (ADHD). MATERIALS AND METHODS This was a population-based cohort study of all pregnancies in Denmark from 1997 to 2008. Information on use of ADHD medication, ADHD diagnosis, and pregnancy outcomes was obtained from nationwide registers. RESULTS We identified 989,932 pregnancies, in which 186 (0.02%) women used MPH/ATX and 275 (0.03%) women had been diagnosed with ADHD but who did not take MPH/ATX. Our reference pregnancies had no exposure to MPH/ATX and no ADHD diagnosis. Exposure to MPH/ATX was associated with an increased risk of spontaneous abortion (SA; ie, death of an embryo or fetus in the first 22 weeks of gestation) (adjusted relative risk [aRR] 1.55, 95% confidence interval [CI] 1.03-2.36). The risk of SA was also increased in pregnancies where the mother had ADHD but did not use MPH/ATX (aRR 1.56, 95% CI 1.11-2.20). The aRR of Apgar scores <10 was increased among exposed women (aRR 2.06, 95% CI 1.11-3.82) but not among unexposed women with ADHD (aRR 0.99, 95% CI 0.48-2.05). CONCLUSION MPH/ATX was associated with a higher risk of SA, but our study indicated that it may at least partly be explained by confounding by indication. Treatment with MPH/ATX was however associated with low Apgar scores <10, an association not found among women with ADHD who did not use MPH/ATX.

Validity of reaction to severe stress and adjustment disorder diagnoses in the Danish Psychiatric Central Research Registry.

Abstract: Aims To assess the validity of reaction to severe stress and adjustment disorder diagnoses registered in the Danish Psychiatric Central Research Register (DPCRR), to examine the documentation of stressful and traumatic events in the medical records, and to investigate the occurrence of stress diagnoses among persons not registered in the DPCRR. Methods Among 101,633 patients diagnosed with International Classification of Diseases, 10th Edition (ICD-10) F43 diagnoses between 1995 and 2011, we selected 50 patients from two hospitals (100 total), comprising one above and one below median age for each diagnosis for five time periods, and reviewed their medical records. We calculated the positive predictive value, comparing registration in the DPCRR with the original medical records, and captured data on stressful life events. Two general practitioners were queried about 50 patients without a stress diagnosis in the DPCRR, regarding whether they had ever received a stress diagnosis. Results The positive predictive value was 58% for acute stress reaction, 83% for posttraumatic stress disorder, 94% for adjustment disorder, 71% for other reactions to severe stress, and 68% for reaction to severe stress, unspecified. In 80% of the records, a stressful or traumatic event was noted. Of 100 patients without an F43 diagnosis in the DPCRR, seven had a stress diagnosis. Conclusion The DPCRR represents a valid and comprehensive resource for research on reaction to severe stress and adjustment disorders, particularly for posttraumatic stress disorder and adjustment disorder.

Surviving severe traumatic brain injury in Denmark: incidence and predictors of highly specialized rehabilitation

Abstract: PURPOSE: To identify all hospitalized patients surviving severe traumatic brain injury (TBI) in Denmark and to compare these patients to TBI patients admitted to highly specialized rehabilitation (HS-rehabilitation) PATIENTS AND METHODS: Patients surviving severe TBI were identified from The Danish National Patient Registry and The Danish Head Trauma Database Overall incidence rates of surviving severe TBI and incidence rates of admission to HS-rehabilitation after severe TBI were estimated and compared Patient-related predictors of no admission to HS-rehabilitation among patients surviving severe TBI were identified using multivariable logistic regression RESULTS: The average incidence rate of surviving severe TBI was 23 per 100,000 person years Incidence rates of HS-rehabilitation were generally stable around 20 per 100,000 person years Overall, 84% of all patients surviving severe TBI were admitted to HS-rehabilitation Female sex, older age, and non-working status pre-injury were independent predictors of no HS-rehabilitation among patients surviving severe TBI CONCLUSION: The incidence rate of hospitalized patients surviving severe TBI was stable in Denmark and the majority of the patients were admitted to HS-rehabilitation However, potential inequity in access to HS-rehabilitation may still be present despite a health care system based on equal access for all citizens Language: en

Validation of International Classification of Diseases coding for bone metastases in electronic health records using technology-enabled abstraction.

Abstract: OBJECTIVE The accuracy of bone metastases diagnostic coding based on International Classification of Diseases, ninth revision (ICD-9) is unknown for most large databases used for epidemiologic research in the US. Electronic health records (EHR) are the preferred source of data, but often clinically relevant data occur only as unstructured free text. We examined the validity of bone metastases ICD-9 coding in structured EHR and administrative claims relative to the complete (structured and unstructured) patient chart obtained through technology-enabled chart abstraction. PATIENTS AND METHODS Female patients with breast cancer with ≥1 visit after November 2010 were identified from three community oncology practices in the US. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of bone metastases ICD-9 code 198.5. The technology-enabled abstraction displays portions of the chart to clinically trained abstractors for targeted review, thereby maximizing efficiency. We evaluated effects of misclassification of patients developing skeletal complications or treated with bone-targeting agents (BTAs), and timing of BTA. RESULTS Among 8,796 patients with breast cancer, 524 had confirmed bone metastases using chart abstraction. Sensitivity was 0.67 (95% confidence interval [CI] =0.63-0.71) based on structured EHR, and specificity was high at 0.98 (95% CI =0.98-0.99) with corresponding PPV of 0.71 (95% CI =0.67-0.75) and NPV of 0.98 (95% CI =0.98-0.98). From claims, sensitivity was 0.78 (95% CI =0.74-0.81), and specificity was 0.98 (95% CI =0.98-0.98) with PPV of 0.72 (95% CI =0.68-0.76) and NPV of 0.99 (95% CI =0.98-0.99). Structured data and claims missed 17% of bone metastases (89 of 524). False negatives were associated with measurable overestimation of the proportion treated with BTA or with a skeletal complication. Median date of diagnosis was delayed in structured data (32 days) and claims (43 days) compared with technology-assisted EHR. CONCLUSION Technology-enabled chart abstraction of unstructured EHR greatly improves data quality, minimizing false negatives when identifying patients with bone metastases that may lead to inaccurate conclusions that can affect delivery of care.

Existing data sources in clinical epidemiology: the Scandinavian Thrombosis and Cancer Cohort.

Abstract: This article was published in the following Dove Press journal: Clinical Epidemiology and available at http://dxdoiorg/102147/CLEPS84279

Systematic reviews with language restrictions and no author contact have lower overall credibility: a methodology study

Abstract: BACKGROUND High-quality systematic reviews (SRs) require rigorous approaches to identify, appraise, select, and synthesize research evidence relevant to a specific question. In this study, we evaluated the association between two steps in the conduct of an SR - restricting the search to English, and author contact for missing data - and the overall credibility of a SR. METHODS All SRs cited by the Endocrine Society's Clinical Practice Guidelines published from October 2006 through January 2012 were included. The main outcome was the overall A Measurement Tool to Assess Systematic Reviews (AMSTAR) score, as a surrogate of SR credibility. Nonparametric Kruskal-Wallis tests and multivariable linear regression models were used to investigate the association between language restriction, author contact for missing data, and the overall AMSTAR score. RESULTS In all, 69 SRs were included in the analysis. Only 31 SRs (45%) reported searching non-English literature, with an average AMSTAR score of 7.90 (standard deviation [SD] =1.64). SRs that reported language restriction received significantly lower AMSTAR scores (mean =5.25, SD =2.32) (P<0.001). Only 30 SRs (43%) reported contacting authors for missing data, and these received, on average, 2.59 more AMSTAR points (SD =1.95) than those who did not (P<0.001). In multivariable analyses, AMSTAR score was significantly correlated with language restriction (beta =-1.31, 95% confidence interval [CI]: -2.62, -0.01, P=0.05) and author contact for missing data (beta =2.16, 95% CI: 0.91, 3.41, P=0.001). However, after adjusting for compliance with reporting guidelines, language restriction was no longer significantly associated with the AMSTAR score. CONCLUSION Fewer than half of the SRs conducted to support the clinical practice guidelines we examined reported contacting study authors or searched non-English literature. SRs that did not conduct these two steps had lower quality scores, suggesting the importance of these two steps for overall SR credibility.

Gastroenteritis attributable to rotavirus in hospitalized Saudi Arabian children in the period 2007-2008.

Abstract: Purpose Rotavirus (RV) is a leading cause of severe gastroenteritis (GE) in children across the world. As there is a lack of epidemiological data for RV gastroenteritis (RVGE) in Saudi Arabia, this hospital-based study was designed to estimate the disease burden of RVGE and assess the prevalent RV types in Saudi children younger than 5 years of age.

Validity of a hospital-based obstetric register using medical records as reference

Abstract: Background Data from hospital-based registers and medical records offer valuable sources of information for clinical and epidemiological research purposes. However, conducting high-quality epidemiological research requires valid and complete data sources. Objective To assess completeness and validity of a hospital-based clinical register - the Obstetric Database - using a national register and medical records as references. Methods We assessed completeness of a hospital-based clinical register - the Obstetric Database - by linking data from all women registered in the Obstetric Database as having given birth in 2013 to the National Patient Register with coverage of all births in 2013. Validity of eleven selected indicators from the Obstetric Database was assessed using medical records as a golden standard. Using a random sample of 250 medical records, we calculated proportion of agreement, sensitivity, specificity, and positive and negative predictive values for each indicator. Two assessors independently reviewed medical records and inter-rater reliability was calculated as proportion of agreement and Cohen's κ coefficient. Results We found 100% completeness of the Obstetric Database when compared to the Danish National Patient Register. Except for one delivery all 6,717 deliveries were present in both registers. Proportion of agreement between the Obstetric Database and medical records ranged from 91.1% to 99.6% for the eleven indicators. The validity measures ranged from 0.70 to 1.00 indicating high validity of the Obstetric Database. κ coefficients from the inter-rater reliability ranged from 0.71 to 1.00. Conclusion Completeness and validity of the Obstetric Database were found acceptable when using the National Patient Register and medical records as golden standards. The Obstetric Database therefore offers a valuable source for examining clinical, administrative, and research questions.

Existing data sources for clinical epidemiology: Scandinavian Cohort for osteonecrosis of the jaw - work in progress and challenges.

Abstract: Osteonecrosis of the jaw (ONJ) is a severe side effect associated with antiresorptive treatment. Monitoring of ONJ using routine databases in Scandinavian countries is a challenge owing to lack of valid algorithms and to heterogeneous referral practices. The aim of this paper is to describe the process of establishing a Scandinavian ONJ Cohort enrolling all ONJ cases related to antiresorptive treatment arising in Denmark, Norway, and Sweden between 2011 and 2019. The initial purpose of the cohort is to support an ongoing pharmacovigilance study of denosumab and zoledronic acid in Denmark, Norway, and Sweden. The three countries, with their 199 clinics, departments, and units of oral and maxillofacial surgery, both hospital-based and freestanding, differ somewhat in referral practices of the ONJ patients. By directly contacting all providers of care to ONJ patients in the three countries, we established a network for reporting incident cases to each country’s research database directly or through a member of the Scandinavian ONJ task force as a liaison. The task force includes a Scandinavian coordinator and three national coordinators collaborating directly with the clinics. A uniform ONJ registration form has been developed, and the relevant medical community has been informed either directly or through presentations at professional meetings. A website with study information is published in each country, and data entry is ongoing. This large-scale systematic uniform registration of ONJ cases in Denmark, Norway, and Sweden, with an underlying total population of more than 20 million people, merged into the Scandinavian ONJ Cohort, will contribute to better knowledge and understanding of this challenging group of patients, and ultimately, help improve patient care. The Scandinavian ONJ Cohort as a whole and its component national ONJ research databases may offer the potential for large-scale multinational intervention and safety studies in the future.

Positive predictive values of the International Classification of Diseases, 10th revision diagnoses of Gram-negative septicemia/sepsis and urosepsis for presence of Gram-negative bacteremia.

Abstract: Background Health care databases are a valuable resource for infectious disease epidemiology if diagnoses are accurately coded. We examined the ability of diagnostic coding to accurately identify Gram-negative bacteremia. Methods We randomly selected 100 patients among 1,703 patients recorded in the Danish National Patient Register with a diagnosis of either "septicemia/sepsis due to other Gram-negative organisms" (International Classification of Diseases, 10th revision [ICD-10] code A41.5) or "urosepsis" (ICD-10 code A41.9B) who had been admitted at Aalborg University Hospital, Denmark between 1994 and 2012. We estimated the positive predictive value (PPV) of these diagnoses for presence of Gram-negative bacteremia, using microbiological results from blood cultures as standard reference. Complementary clinical information was obtained from the medical records. Results Of the 100 patients registered with Gram-negative septicemia/sepsis or urosepsis, 72 had blood culture confirmed Gram-negative bacteremia, four patients had monomicrobial Gram-positive bacteremia, 21 patients had a negative blood culture, and three had no blood culture taken. The overall PPV of a blood culture confirmed Gram-negative bacteremia diagnosis was 72% (95% confidence interval [CI]: 62%-81%); for ICD-10 code A41.5 it was 86% (95% CI: 74%-94%) and for ICD-10 code A41.9B it was 55% (95% CI: 39%-70%). The highest PPV was achieved for diagnoses registered in the most recent calendar period (2009-2012) and for secondary discharge diagnoses. Conclusion Our findings indicated good agreement between ICD-10 code A41.5 "septicemia/sepsis due to other Gram-negative organisms" and Gram-negative bacteremia, whereas ICD-10 code A41.9B "urosepsis" was not suited for identification of Gram-negative bacteremia.

A common data model to assess cardiovascular hospitalization and mortality in atrial fibrillation patients using administrative claims and medical records.

Abstract: Purpose Atrial fibrillation/flutter (AF) is frequently associated with cardiovascular comorbidities. Observational health care databases are commonly used for research purposes in studies of quality of care, health economics, outcomes research, drug safety, and epidemiology. This retrospective cohort study applied a common data model to administrative claims data (Truven Health Analytics MarketScan® claims databases [MS-Claims]) and electronic medical records data (Geisinger Health System’s MedMining electronic medical record database [MG-EMR]) to examine the risk of cardiovascular hospitalization and all-cause mortality in relation to clinical risk factors in recent-onset AF and to assess the consistency of analyses for each data source.

Validation of second trimester miscarriages and spontaneous deliveries

Abstract: OBJECTIVE To validate the diagnosis of second trimester miscarriages/deliveries (16+0 weeks to 27+6 weeks of gestation) recorded as miscarriages in the Danish National Patient Registry or spontaneous deliveries in the Danish Medical Birth Registry, and asses the validity of risk factors, pregnancy complications, and cerclage by review of medical records. MATERIALS AND METHODS In a cohort of 2,358 women with a second trimester miscarriage/delivery in first pregnancy and a subsequent delivery during 1997-2012, we reviewed a representative sample of 682 medical records. We searched for clinically important information and calculated positive predictive values of the registry diagnoses stratified by type of registry, as well as sensitivity, specificity, positive predictive value, and kappa coefficients of risk factors, pregnancy complications, and cerclage. RESULTS Miscarriage/spontaneous delivery in the second trimester was confirmed in 621/682 patients (91.1%). Pregnancy complications in second trimester miscarriages were underreported, resulting in low sensitivities and poor to moderate agreements between records and registries. There was a good agreement (kappa >0.6) between medical records and the registries regarding risk factors and cerclage. The diagnosis of cervical insufficiency had "moderate" kappa values for both miscarriages and deliveries (0.55 and 0.57). CONCLUSION Spontaneous second trimester deliveries and miscarriages recorded in the registers were confirmed by medical records in 91%, but register-based information on pregnancy complications need to be improved. We recommend that all pregnancies ending spontaneously beyond the first trimester are included in the national birth registry and described by appropriate variables.

Oxaliplatin-based first-line chemotherapy is associated with improved overall survival compared to first-line treatment with irinotecan-based chemotherapy in patients with metastatic colorectal cancer - Results from a prospective cohort study.

Abstract: Purpose: Several randomized trials investigating the preferable first-line combination che motherapy regimen for metastatic colorectal cancer have shown inconsistent findings. Because a substantial number of patients are still being treated with “chemo-only” first-line therapies without targeted agents, we compared overall survival (OS) of patients treated in routine practice with oxaliplatin–fluoropyrimidine and irinotecan–fluoropyrimidine. Patients and methods: Using the database of the Tumor Registry Colorectal Cancer, we identified 605 patients with metastatic colorectal cancer who received first-line fluoropyrimidine combination chemotherapy with either oxaliplatin (n=430) or irinotecan (n=175). The Tumor Registry Colorectal Cancer is a cohort study that prospectively documents treatment of colorectal cancer by office-based medical oncologists in Germany and has recruited over 5,000 patients. OS was estimated using the Kaplan–Meier method, and a multivariate Cox proportional hazard model was used to adjust for potentially confounding variables. Results: Median OS was 26.8 (95% confidence interval [CI] 22.4–31.9) months with an oxalipla tin–fluoropyrimidine combination and 18.3 (95% CI 15.1–23.2) months with irinotecan–fluoropy rimidine first-line “chemo-only” therapy. Median progression-free survival was 9.0 (8.1–10.2) and 7.9 (7.2–10.2) months, respectively. The difference in OS was confirmed if analysis was restricted to patients with synchronous metastases (no prior treatment). Among other variables, proportion of patients receiving any second-line therapy did not differ between groups. Oxaliplatin-based first-line therapy was associated with improved OS in multivariate analysis adjusted for potentially confounding variables (hazard ratio 0.678, 95% CI 0.510–0.901, P=0.007). Conclusion: In clinical routine practice, first-line treatment with oxaliplatin–fluoropyrimidine combination chemotherapy compared to irinotecan–fluoropyrimidine combination is associated with improved survival in patients with metastatic colorectal cancer, independent of all examined potentially confounding factors.

Raynaud phenomenon and mortality: 20+ years of follow-up of the Charleston Heart Study cohort.

Abstract: BACKGROUND Raynaud phenomenon (RP) is a temporary vasoconstrictive condition that often manifests itself in the fingers in response to cold or stress. It often co-occurs with certain chronic diseases that impact mortality. Our objective was to determine whether RP has any independent association with survival. METHODS From 1987-1989, a total of 830 participants of the Charleston Heart Study cohort completed an in-person RP screening questionnaire. Two definitions of RP were used: a broad definition that included both blanching (pallor) and cyanotic color changes and a narrow definition that included only blanching. All-cause and cardiovascular disease (CVD) mortality were compared between subjects with and without RP using race-specific survival models that adjusted for age, sex, baseline CVD, and 10-year risk of coronary heart disease. RESULTS Using the narrow RP definition, we identified a significant interaction between older age and the presence of RP on all-cause mortality. In the broad RP definition model, the presence of RP was not associated with CVD mortality among blacks; however, among whites, the presence of RP was associated with a 1.6-fold increase in the hazard associated with CVD-related death (hazard ratio: 1.55, 95% confidence interval: 1.10-2.20, P=0.013). CONCLUSION RP was independently associated with mortality among older adults in our cohort. Among whites, RP was associated with increased CVD-related death. It is possible that RP may be a sign of undiagnosed vascular disease.

Tuberculosis case finding in first-degree relative contacts not living with index tuberculosis cases in Kampala, Uganda.

Abstract: Purpose To assess the prevalence of pulmonary tuberculosis among first-degree relative (FDR) contacts not living with tuberculosis (TB) cases. Methods A cross-sectional analysis of household contacts living with an index TB case and FDR contacts living outside of households in Kampala, Uganda, is presented. Results A total of 177 contacts (52 FDRs and 125 index household contacts) of 31 TB cases were examined. Compared with index household contacts, FDR contacts were older, more likely to be TB symptomatic (50% vs 33%), had a higher percentage of abnormal chest X-rays (19% vs 11%), sputum smear positive (15% vs 5%), and many similar epidemiologic risk factors, including HIV infection (13% vs 10%). Contact groups had similar pulmonary tuberculosis prevalence: 9.6% in FDR vs 10.4% in index household contacts and similar Mycobacterium tuberculosis infection: 62% in FDR vs 61% in index households. Conclusion TB is common among FDR contacts. High TB prevalence justifies targeting FDRs during household contact investigations. Combining TB active-case finding among FDR contacts with household contact investigation in low-income setting is feasible. This should be part of national TB control program strategies for increasing TB case-detection rates and reducing community TB transmission and death.

The Danish National Prescription Registry in studies of a biological pharmaceutical: palivizumab - validation against two external data sources.

Abstract: BACKGROUND: National prescription databases are important tools in pharmacoepidemiological studies investigating potential long-term adverse events after drug use. Palivizumab is a biological pharmaceutical used as passive prophylaxis against severe infection with respiratory syncytial virus in high-risk children. OBJECTIVE: To assess the registration of palivizumab in the Danish National Prescription Registry (DNPR) and to examine if palivizumab reimbursement data obtained from the Danish Health and Medicines Authority could serve as a supplement to data from the DNPR. METHODS: Registration of palivizumab exposure in the DNPR between 1999 and 2010 was compared to two external data sources: registration of palivizumab exposure in medical records, and palivizumab reimbursement data. RESULTS: During the study period, 182 children with palivizumab exposure were registered in the DNPR. A total of 207 children were registered for palivizumab reimbursement. The sensitivity of palivizumab registration in the DNPR was 26% (20%-34%), and the specificity of no palivizumab registration in the DNPR was 97% (94%-99%), with data from the medical record as the reference. Palivizumab registration sensitivity in reimbursement data was 29% (22%-36%), and the specificity of no palivizumab registration in the DNPR was 97% (94%-99%), with data from the medical record as the reference. CONCLUSION: Exposure to palivizumab was underestimated in the DNPR. Reimbursement data are a readily accessible data supplement, which only slightly increased the sensitivity of palivizumab registration in the DNPR. Our findings underline the need to improve DNPR information concerning drugs administered in hospitals.

Existing data sources for clinical epidemiology: the Danish Patient Compensation Association database.

Abstract: Any patient in the Danish health care system who experiences a treatment injury can make a compensation claim to the Danish Patient Compensation Association (DPCA) free of charge. The aim of this paper is to describe the DPCA database as a source of data for epidemiological research. Data to DPCA are collected prospectively on all claims and include information on patient factors and health records, system factors, and administrative data. Approval of claims is based on injury due to the principle of treatment below experienced specialist standard or intolerable, unexpected extensiveness of injury. Average processing time of a compensation claim is 6–8 months. Data collection is nationwide and started in 1992. The patient’s central registration system number, a unique personal identifier, allows for data linkage to other registries such as the Danish National Patient Registry. The DPCA data are accessible for research following data usage permission and make it possible to analyze all claims or specific subgroups to identify predictors, outcomes, etc. DPCA data have until now been used only in few studies but could be a useful data source in future studies of health care-related injuries.