Existing data sources for clinical epidemiology: Aarhus University Prescription Database

Population-based prescription databases in Nordic countries have become a mainstay of epidemiologic research. Denmark has both national and regional population-based prescription databases. Aarhus University Prescription Database collects data on reimbursed medications dispensed at all community pharmacies of the North Denmark Region and the Central Denmark Region. The regions have a combined population of 1.8 million inhabitants, or one-third of the Danish population. Denmark’s primary health care sector, which includes general practitioners, specialists, and dentists, generates about 96% of the prescription sales, most of which are reimbursable and are dispensed by the community pharmacies. The Aarhus University Prescription Database combines the region’s pharmacy records in a single database, maintained and updated for research purposes. Each dispensation record contains patient-, drug-, and prescriber-related data. Dispensation records retain patients’ universal personal identifier, which allows for individual-level linkage to all Danish registries and medical databases. The linked data have many applications in clinical epidemiology, including drug utilization studies, safety monitoring, etiologic research, and validation studies

Accuracy of plain radiography in detecting fractures in older individuals after low-energy falls: current evidence

BackgroundOlder individuals sustaining low-energy falls (LEF) and presenting to the emergency department (ED) demand straightforward diagnostic measures for injury detection. Plain radiography (XR) series for diagnosis of fall-related injuries are standard of care, but frequently subsequent CT examination is required for diagnostic assurance. A systematic database search of diagnostic accuracy of XR for detection of fractures in older LEF patients was performed.MethodsWe searched PubMed, Embase, Cochrane Library, WHO International Clinical Trial Platform, and Clinical trials.gov databases from inception to January 2020 for studies including older patients (>= 65 years) with LEF and obtaining CT examination and XR of the skeleton in an ED setting.ResultsFrom 8944 references screened, 11 studies met the criteria for inclusion. Performance of XR for detection of fractures of the pelvic ring and hip was analyzed in nine studies, two studies investigated XR performance to detect rib fractures, and two studies compared diagnostic accuracy of thoracolumbar spine XR. Sensitivity estimates ranged from 10% to 58% and specificity estimates from 55% to 100%. Clinical and statistical heterogeneity was significant among included studies, with an overall considerable risk of bias.DiscussionHigh-quality evidence on accurate imaging strategies in older patients with LEF is lacking to date. XR is missing a reasonable amount of fractures of the pelvic ring, rib cage, and thoracic and lumbar spine. However, the utility of first-line CT imaging and the benefit of diagnosing every fracture is unknown, demanding high-quality prospective trials considering patient-oriented outcome as well

Science for a wilder Anthropocene: synthesis and future directions for trophic rewilding research

Trophic rewilding is an ecological restoration strategy that uses species introductions to restore top-down trophic interactions and associated trophic cascades to promote self-regulating biodiverse ecosystems. Given the importance of large animals in trophic cascades and their widespread losses and resulting trophic downgrading, it often focuses on restoring functional megafaunas. Trophic rewilding is increasingly being implemented for conservation, but remains controversial. Here, we provide a synthesis of its current scientific basis, highlighting trophic cascades as the key conceptual framework, discussing the main lessons learned from ongoing rewilding projects, systematically reviewing the current literature, and highlighting unintentional rewilding and spontaneous wildlife comebacks as underused sources of information. Together, these lines of evidence show that trophic cascades may be restored via species reintroductions and ecological replacements. It is clear, however, that megafauna effects may be affected by poorly understood trophic complexity effects and interactions with landscape settings, human activities, and other factors. Unfortunately, empirical research on trophic rewilding is still rare, fragmented, and geographically biased, with the literature dominated by essays and opinion pieces. We highlight the need for applied programs to include hypothesis testing and science-based monitoring, and outline priorities for future research, notably assessing the role of trophic complexity, interplay with landscape settings, land use, and climate change, as well as developing the global scope for rewilding and tools to optimize benefits and reduce human–wildlife conflicts. Finally, we recommend developing a decision framework for species selection, building on functional and phylogenetic information and with attention to the potential contribution from synthetic biology

Association of Apgar score at five minutes with long-term neurologic disability and cognitive function in a prevalence study of Danish conscripts

<p>Abstract</p> <p>Background</p> <p>Apgar score is used for rapid assessment of newborns. Low five-minute Apgar score has been associated with increased risk of severe neurologic outcome, but data on milder outcomes, particularly in the long term, are limited. We aimed to examine the association of five-minute Apgar score with prevalence of neurologic disability and with cognitive function in early adulthood.</p> <p>Methods</p> <p>We conducted a prevalence study among draft-liable men born in Denmark in 1978–1983 and presenting for the mandatory army evaluation in a northern Danish conscription district. We linked records of this evaluation, which includes medical exam and intelligence testing, with the conscripts' records in the Medical Birth Registry, containing perinatal data. We examined prevalence of neurologic disability and of low cognitive function according to five-minute Apgar score.</p> <p>Results</p> <p>Less than 1% (136/19,559) of the conscripts had 5-minute Apgar scores <7. Prevalence of neurologic disability was 2.2% (435/19,559) overall; among conscripts with Apgar scores <7, 7–9, and 10 (reference), it was 8.8%, 2.5%, and 2.2% respectively. The corresponding prevalences of low cognitive function (intelligence test score in the bottom quartile) were 34.9%, 27.2%, and 25.0%. The outcomes were more prevalent if Apgar score <7 was accompanied by certain fetal or obstetric adversities. After accounting for perinatal characteristics, 5-mintue Apgar score <7 was associated with prevalence ratios of 4.02 (95% confidence interval: 2.24; 7.24) for neurologic disability and 1.33 (0.94; 1.88) for low cognitive function.</p> <p>Conclusion</p> <p>A five-minute Apgar score <7 has a consistent association with prevalence of neurologic disability and with low cognitive function in early adulthood.</p

Conditioning on future exposure to define study cohorts can induce bias: the case of low-dose acetylsalicylic acid and risk of major bleeding

A principle of cohort studies is that cohort membership is defined by current rather than future exposure information. Pharmacoepidemiologic studies using existing databases are vulnerable to violation of this principle. We evaluated the impact of using data on future redemption of prescriptions to determine cohort membership, motivated by a published example seeking to emulate a “per-protocol” association between continuous versus never use of low-dose acetylsalicylic acid (ASA) and major bleeding (e.g., cerebral hemorrhage or gastrointestinal bleeding)

Correspondence between general practitioner-reported medication use and timing of prescription dispensation

Epidemiologic studies often rely on drug dispensation records to measure medication intake. We aimed to estimate correspondence between general practitioner (GP)-reported treatment and timing of prescription dispensation. From seven GPs in northern Denmark, we obtained 317 prescription records for 286 patients treated with ten commonly prescribed medication types for chronic diseases. We linked the GP-reported information to the regional prescription database to retrieve patients’ prescription records both prospectively and retrospectively in relation to the GP-reported date of treatment (index date, August 20, 2008 for all patients). We computed overall and medication-specific correspondence between GP-reported treatment and the timing of dispensation. We computed correspondence based on both exact medication and therapeutic subgroup agreement. The correspondence for dispensation within ±90 days of GP-reported treatment was 0.81 (95% confidence interval = 0.76–0.85) with variation by medication type, ranging from 0.55 for ACE-inhibitors to 1.00 for oral glucose-lowering agents. The correspondence was greater when analyzed within therapeutic groups than when analyzed for exact medications within these groups

Low-Milliampere CT Fluoroscopy-Guided Percutaneous Drainage Placement after Pancreatic Surgery: Technical and Clinical Outcome in 133 Consecutive Patients during a 14-Year Period

(1) Purpose: To retrospectively assess the technical and clinical outcome of patients with symptomatic postoperative fluid collections after pancreatic surgery, treated with CT-guided drainage (CTD). (2) Methods: 133 eligible patients between 2004 and 2017 were included. We defined technical success as the sufficient drainage of the fluid collection(s) and the absence of peri-interventional complications (minor or major according to SIR criteria). Per definition, clinical success was characterized by normalization of specific blood parameters within 30 days after the intervention or a decrease by at least 50% without requiring additional surgical revision. C-reactive protein (CRP), Leukocytes, Interleukin-6, and Dose length product (DLP) for parts of the intervention were determined. (3) Results: 97.0% of 167 interventions were technically successful. Clinical success was achieved in 87.5% of CRP, in 78.4% of Leukocytes, and in 87.5% of Interleukin-6 assessments. The median of successful decrease was 6 days for CRP, 5 days for Leukocytes, and 2 days for Interleukin-6. No surgical revision was necessary in 93.2%. DLP was significantly lower in the second half of the observation period (total DLP: median 621.5 mGy*cm between 2011–2017 vs. median 944.5 mGy*cm between 2004–2010). (4) Conclusions: Technical success rate of CTD was very high and the clinical success rate was fair to good. Given an elderly and multimorbid patient cohort, CTD can have a temporizing effect in the postoperative period after pancreatic surgery. Reducing the radiation dose over time might reflect developments in CT technology and increased experience of interventional radiologists

Akv murine leukemia virus enhances bone tumorigenesis in hMT-c-fos-LTR transgenic mice

AbstracthMt-c-fos-LTR transgenic mice (U. Rüther, D. Komitowski, F. R. Schubert, and E. F. Wagner. Oncogene 4, 861–865, 1989) developed bone sarcomas in 20% (3/15) of females at 448 ± 25 days and in 8% (1/12) of males at 523 days. After infection of newborns with Akv, an infectious retrovirus derived from the ecotropic provirus of the AKR mouse, 69% (20/28) of female animals and 83% (24/29) of males developed malignant fibrous-osseous tumors. The tumors in infected transgenics developed with higher frequency and a 200-days shorter mean tumor latency period. The hMt-c-fos-LTR transgene was expressed in all the fibrous-osseous tumors. They also showed newly integrated Akv proviruses, but in most tumors Akv was detected and expressed in only a small number of the tumor cells. Wild-type C3H mice infected with Akv developed benign osteomas with an incidence of 33% and a latency period of 474 days. The data indicate that Akv exerts distinct pathogenic effects on the skeleton. In hMt-c-fos-LTR transgenic mice, predisposed to bone sarcomagenesis, Akv acts synergistically with the fos transgene, resulting in the development of fibrous-osseous tumors