Danish Research Research Articles

Maternal use of mild analgesics during pregnancy associated with reduced anogenital distance in sons: a cohort study of 1027 mother-child pairs.

Is maternal use of mild analgesics in pregnancy associated with anogenital distance (AGD)-the distance from the anus to the genitals-in the offspring? Maternal use of mild analgesics [especially simultaneous use of paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs)] during pregnancy was associated with a shorter AGD in boys whereas no effect was found in girls. Mild analgesics including paracetamol (acetaminophen) and NSAIDs (e.g. ibuprofen and acetyl salicylic acid) have endocrine disrupting properties and in utero exposure reduces AGD in male rats. In humans, maternal exposure has been associated with cryptorchidism and hypospadias in male offspring but no studies have examined AGD. A prospective birth cohort study. Between 2010 and 2012, 2500 pregnant women were recruited from the Odense Child Cohort. Children were examined 3 months after the expected date of birth. Pregnant women were asked about use of medication including mild analgesics (paracetamol and NSAID) during pregnancy at recruitment (gestational age (GA) week 10-27) and at GA week 28. AGD and penile width were measured 3 months after expected date of birth by trained personnel. A total of 1027 women answered both questionnaires and their children were examined. Associations between prenatal exposure to mild analgesics and AGD and penile width were estimated using multivariable linear regression adjusting for age and weight-for-age SD score. A total of 40% of the women reported use of paracetamol and/or NSAIDs (4.4%) during the first 28 weeks of pregnancy. Exposure to analgesics during pregnancy was associated with a reduced AGD in boys, although statistically significant only for NSAIDs. The association was significant among 20 boys exposed to both paracetamol and NSAIDs (AGD -4.1 mm; CI 95%: -6.4; -1.7). Maternal intake of analgesics did not show any clear association with AGD in female offspring. No effect on penile width was found. Only 27 boys and 18 girls were exposed to NSAIDs and most of them were also exposed to paracetamol. This makes it impossible to distinguish between exposures to NSAIDs alone and a potential mixture effect. Moreover, use of mild analgesics was self-reported up to 2 months after intake, which could have caused misclassification of exposure but is probably not associated with AGD as this was unknown to the women at time of reply to the questionnaire thereby underestimating the association. Confounding by indication may also explain our findings, as the condition for which the analgesic was taken may be associated with a reduction in AGD, rather than the use of the analgesic medication. This is the first study to report such an association in humans and further studies are needed to confirm our findings. A negative association was observed between exposure to analgesics during pregnancy and AGD in boys, suggesting disruption of androgen action. The health implications of a shorter AGD are still uncertain, but in cross-sectional studies among adult men a shorter AGD is associated with poorer semen quality and lower testosterone. As 41% of the women used these painkillers the finding are of public health importance and pregnant women should be advised about the potentially harmful effects of painkiller use. The study was funded by the Danish Environmental Protection Agency by way of the Center on Endocrine Disruptors Danish Center for Hormone Disrupting Chemicals, the Danish Foundation for Scientific Innovation and Technology (09-067180), the Danish Research Council (4004-00352B_FSS), Novo Nordic Foundation (NNF15OC0017734), Ronald McDonald Children Foundation, K.A. Rohde's and wife's Foundation, Odense University Hospital and Region of Southern Denmark, Municipality of Odense, the Danish Council for Strategic Research, Program Commission on Health, Food and Welfare (2101-08-0058), Odense University Hospital Research Foundation and Odense Patient data Exploratory Network (OPEN). The authors declare they have no competing interests. Not applicable.

Author’s reply to Beekmann

Beekmann highlights the range of media responses to the Danish research on alcohol consumption and fecundity.1 2 As is often the case, the headlines oversimplified the findings, with polarised, conflicting summaries. It’s …

The Danish Heart Failure Registry

Aim of databaseThe aim of the Danish Heart Failure Registry (DHFR) is to monitor and improve the care of patients with incident heart failure (HF) in Denmark.Study populationThe DHFR includes inpatients and outpatients (≥18 years) with incident HF. Reporting to the DHFR is mandatory for the Danish hospital departments treating patients with incident HF. Final decision to register a patient in the DHFR is made by a cardiologist to ensure the validity of the diagnosis. Approximately 42,400 patients with incident HF were registered in the DHFR in July 2015.Main variables and descriptive dataThe main variables recorded in the DHFR are related to the indicators for quality of care in patients with incident HF: performance of echocardiography, functional capacity (New York Heart Association functional classification), pharmacological therapy (angiotensin converting enzyme/angiotensin II antagonist inhibitors, beta-blockers, and mineralocorticoid receptor antagonist), nonpharmacological therapy (physical training, patient education), 4-week readmission rate, and 1-year mortality. Furthermore, basic patient characteristics and prognostic factors (eg, smoking and alcohol) are recorded. At the annual national audit in the DHFR, the indicators and standards for good clinical quality of care for patients with HF are discussed, and recommendations are reported back to clinicians to promote quality improvement initiatives. Furthermore, results and recommendations are communicated to the public in an annual report. All standards for the quality indicators have been met at a national level since 2014. Indicators for treatment status 1 year after diagnosis are under consideration (now prevalent HF).ConclusionThe DHFR is a valuable tool for continuous improvement of quality of care in patients with incident HF in Denmark. Furthermore, it is an important resource for the Danish registry-based HF research.

High fruit intake, lower alcohol consumption associated with lower breast cancer risk

Researchers in 2 linked studies recently published in BMJ have revealed new data on the relation of alcohol and diet with breast cancer and heart disease.1, 2 The first study found that high fruit consumption during adolescence is associated with lower breast cancer risk, whereas the second reports that increased alcohol intake in later life is associated with an increase in breast cancer. Evidence about whether fruit and vegetable intake protects against breast cancer is conflicting. Most studies in this area have assessed intake during midlife and later, which may be after the period when breast tissue is most vulnerable to carcinogenic influences. As a result, researchers examined whether fruit and vegetable consumption would affect subsequent breast cancer risk. In the first study, participants included more than 90,000 premenopausal women aged 27 to 44 years from the Nurses' Health Study II who completed a questionnaire in 1991 on diet as well as more than 44,000 who completed a questionnaire in 1998 that focused on their diet during adolescence. The investigators concluded that high fruit consumption during adolescence (2.9 vs 0.5 servings per day) was associated with an approximately 25% lower risk of premenopausal breast cancer diagnosed in middle age. The association with adolescent fruit intake was stronger for both estrogen and progesterone receptor-negative cancers than estrogen and progesterone receptor-positive cancers. Specifically, apple, banana, and grape consumption during adolescence and orange and kale consumption during early adulthood were significantly associated with a reduced breast cancer risk; however, there was no link between the intake of fruit juice in either adolescence or early adulthood and risk. In an accompanying editorial, University of Oxford researchers note that although much more evidence is needed before conclusions can be drawn about the protective associations between adolescent fruit intake and breast cancer risk, fruit and vegetable intake should continue to be encouraged at all ages because of the known beneficial health effects.3 In the second study, Danish researchers analyzed the effect of a change in alcohol intake on the risk of breast cancer and heart disease. They followed the health of nearly 22,000 postmenopausal women in Denmark and found that women who increased their alcohol intake by 2 drinks per day over 5 years had an approximately 30% increased risk of breast cancer but an approximately 20% decreased risk of coronary heart disease in comparison with women who had stable alcohol intake. Decreased alcohol intake in women during the 5-year period, however, was not significantly associated with the risk of either breast cancer or coronary heart disease. The authors note that although their findings support the theory that alcohol is associated with breast cancer and coronary heart disease risk in opposite directions, the true effect of alcohol on ischemic heart disease is not certain. They add that although low to moderate alcohol consumption may provide some benefit to the heart, this is outweighed by an increased risk of breast cancer and other morbidities. Furthermore, heart disease risk can be substantially reduced by other lifestyle changes and drugs such as statins.

Annual report of the Emerging Risks Exchange Network 2015

Annual report of the Emerging Risks Exchange Network 2015

An assessment of Palaeogene and Neogene clay deposits in Denmark as possible host rocks for final disposal of low- and intermediate-level radioactive waste

Abstract In Denmark, mapping and preliminary investigations of Palaeogene and Early Neogene clay deposits have been performed over the past 5 years. The goal was to locate potential host rocks for the final disposal of low- and intermediate-level radioactive waste from the Danish Research Centre Risø, which has to be decommissioned within the next 5–8 years. Five areas with low-permeability Paleocene and Oligocene clay formations, situated in northern Jylland, NE Fyn and southern Lolland, not far from the Baltic coast at Femern Belt, have been suggested. The clay formations are between 75 and 150 m thick, and have large lateral distribution. They are covered by thin layers of glacial clayey tills and the shallow depth to the clay formations is attractive, partly because they are easy to access and partly because there are no groundwater aquifers situated above or below the clay deposits. The paper gives an overall review of the characteristics of the six different clay formations within four of the areas.

Is the Volume of the Caudate Nuclei Associated With Area of Secondary Hyperalgesia? - Protocol for a 3-Tesla MRI Study of Healthy Volunteers.

BackgroundExperience and development of pain may be influenced by a number of physiological, psychological, and psychosocial factors. In a previous study we found differences in neuronal activation to noxious stimulation, and microstructural neuroanatomical differences, when comparing healthy volunteers with differences in size of the area of secondary hyperalgesia following a standardized burn injury.ObjectiveWe aim to investigate the degree of association between the volume of pain-relevant structures in the brain and the size of the area of secondary hyperalgesia following brief thermal sensitization.MethodsThe study consists of one experimental day, in which whole-brain magnetic resonance imaging (MRI) scans will be conducted including T1-weighed three-dimensional anatomy scan, diffusion tensor imaging, and resting state functional MRI. Before the experimental day, all included participants will undergo experimental pain testing in a parallel study (Clinicaltrials.gov Identifier: NCT02527395). Results from this experimental pain testing, as well as the size of the area of secondary hyperalgesia from the included participants, will be extracted from this parallel study.ResultsThe association between the volume of pain-relevant structures in the brain and the area of secondary hyperalgesia will be investigated by linear regression of the estimated best linear unbiased predictors on the individual volumes of the pain relevant brain structures.ConclusionsWe plan to investigate the association between experimental pain testing parameters and the volume, connectivity, and resting state activity of pain-relevant structures in the brain. These results may improve our knowledge of the mechanisms responsible for the development of acute and chronic pain.ClinicalTrialDanish Research Ethics Committee (identifier: H-15010473). Danish Data Protection Agency (identifier: RH-2015-149). Clinicaltrials.gov NCT02567318; http://clinicaltrials.gov/ct2/show/NCT02567318 (Archived by WebCite at http://www.webcitation.org/6i4OtP0Oi)

Governing homo economicus: risk management among young unemployed people in the Danish welfare state

In this article, I examine how young unemployed people deal with the risk of unemployment in the Danish welfare state, focusing on two main issues. I examine the technologies currently being used in the unemployment system to manage youth unemployment and I explore how the young unemployed people who are the subject of these technologies understand and react to them. I also consider the affective work, which underpins these technologies and the ways this shapes the framing of risks. In this article, I draw on a Danish research study (2014–2015) that examined the ways in which the Danish unemployment fund operated and I used in-depth interviews to explore the ways in which 33 young unemployed Danes interacted with the unemployment fund. Using the conceptual tools provided by the governmentality risk perspective, I analysed the relationship between institutionalised risk management and individual risk management. I found that the management of risk at the institutional level invoked the use of a screening tool that categorised young unemployed people into risk groups and this categorisation determined the intervention the young unemployed persons received. I found that in the new unemployment system, young unemployed people were treated not only as homo economicus, that is, rational actors responding to economic incentives but they were also seen as sensitive beings whose feelings and affects could be shaped by technologies empowering and motivating them in order to enable them to manage their own risk of unemployment more effectively. This psychologised the issue of unemployment.

Renal Urea Transport Alterations with Prolonged Renal Urea Transport Alterations with Prolonged Hyperglycaemia

PurposeTo explore whether hyperpolarized urea could serve as a possible imaging bio‐marker of the renal function via the intra‐renal osmolality gradient in diabetes.MethodsThirteen 250 g female wistar rats were randomly grouped in a diabetic group (four weeks of untreated type‐1 diabetes) of six animals and a healthy control group of seven animals. Diabetes was induced by an i.v. injection of freshly prepared streptozotocin (STZ; 55 mg/kg body weight). Rats were considered diabetic when the blood glucose levels exceeded 15 mmol/L at 48 h after injection of STZ. For the MR examinations, the rats were anesthetized and a tail vein catheterisation was performed. The MR examination was performed with a 9.4 T pre‐clinical MR system (Agilent, UK) equipped with a dual tuned 13C/1H volume rat coil (Doety scientic, US). Urea was polarized in a 5T SPINLab (GE Healthcare, Brøndby, DK) to a reproducible polarization of more than 40% [1]. The hyperpolarized sample was rapidly dissolved and a final solution of 1.5 ml hyperpolarized urea was injected intravenously to the animal over a period of 15 sec. A 1H gradient echo coronal and axial scan was acquired (TR/TE 100 ms/2.6 ms, flip 20°, FOV 60 mm2, matrix 128 × 128). The scan was performed as an anatomical 1H scout (Figure 1A). 3D 13C balanced steady state free precession (BSSFP) imaging sequences were performed (flip 15°, TR/TE 5.4 ms/2.7 ms, sw 20kHz, FOV 60 mm3, matrix 48×48×48 covering both kidneys) and initiated 35 s after the start of hyperpolarized [13C,15N]urea injection (Figure 1B).At the time of euthanasia, both kidneys were rapidly dissected. Cortex and inner medulla (IM) were collected separately and analyses for different urea transporters were done with qPCR.ResultsThe rats administered with STZ, all developed sustained hyperglycaemia within 48 hours. 3D balanced steady state 13C MRI images of hyperpolarized urea showed a cortico‐medullary urea gradient (Figure 1) with an accumulation of urea in the medullary and pelvic segments. A significant higher urea‐to‐total‐signal in the cortical region (p=0.008) concomitant with a significant decreased urea‐to‐total‐signal in the pelvic region (p=0.03) were found in the diabetic animals (Figure 2A). This resulted in a reduced intra‐renal urea‐to‐cortical distribution in the medulla (p=0.04) and pelvic (p=0.002) regions in the diabetics when compared to controls (Figure 2B). A significant intra‐renal increased urea accumulation from the cortex to the pelvis was found in both the diabetic and the control kidney, (p<0.0001) (Figure 2B). The transcription levels of the urea transporters were all significantly altered in the diabetic rat kidney compared to the control animals (Figure 3).ConclusionThis study illustrated the potential of using hyperpolarized urea in estimating renal function, by showing a decreased intra‐renal distribution after prolonged hyperglycemia. This was consistent with the findings of a gradually decreasing function found in the diabetic kidney. The transcription of the urea transporters was generally up‐regulated, supporting the increased oxygen consumption. In contrast, the lower urea gradient in the diabetic kidney, compared to the healthy controls, verified the reduced renal function after four weeks of diabetes.Support or Funding InformationThe Danish Research Council supported the study.

Collaboration between relatives of elderly patients and nurses and its relation to satisfaction with the hospital care trajectory

Danish researchers investigated how collaboration between relatives and nurses affects carers’ experiences during admissions. The researchers also examined the relationship between carer satisfaction, carers’ characteristics and specific aspects of collaboration.

Compensated reduction in Leydig cell function is associated with lower semen quality variables: a study of 8182 European young men

Is the Leydig cell function of young European men associated with semen quality? Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower semen quality. Semen quality of young European men shows a heterogeneous pattern. Many have sperm counts below and in the lower WHO reference where there nevertheless is a significant risk of subfecundity. Little is known about differences in Leydig cell function between men with semen quality below and within the WHO reference range. A coordinated, cross-sectional population-based study of 8182 men undertaken in 1996-2010. Young men (median age 19.1 years) were investigated in centres in Denmark, Estonia, Finland, Germany Latvia, Lithuania, and Spain. The men originated from the general populations, all were young, almost all were unaware of their fecundity and each provided a semen and blood sample. Associations between semen parameters and serum levels of testosterone and luteinising hormone (LH), calculated free testosterone, and ratios between serum testosterone and LH were determined. Serum testosterone levels were not associated with sperm concentrations, total sperm counts, or percentage of motile or morphologically normal spermatozoa. There was an inverse association between the semen parameters and serum LH levels, and accordingly a positive association to testosterone/LH ratio and calculated-free-testosterone/LH ratio. The size of the study mitigates the intra-individual variability concern. The distinction between different sub-categories of sperm motility and sperm morphology is subjective despite training. However, inter-observer variation would tend towards non-differential misclassification and would decrease the likelihood of detecting associations between reproductive hormone levels and semen variables, suggesting that the presented associations might in reality be even stronger than shown. Although we adjusted for confounders, we cannot of course exclude that our results can be skewed by selection bias or residual confounding. Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower semen quality. This is apparent even within the WHO reference range of semen quality. It is unknown whether impaired Leydig cell function in young men may confer an increased risk of acquired testosterone deficiency later in life. Support from The Research Fund of Rigshospitalet (grant no. R42-A1326) to N.J. made this study possible. The background studies of young men have been supported economically by several grants. ITALIC! Denmark: The European Union (contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603 and most recently FP7/2007-2013, DEER Grant agreement no. 212844), The Danish Research Council (grants nos. 9700833 2107-05-0006), The Danish Agency for Science, Technology and Innovation (Grant no. 271070678), Rigshospitalet (Grant no. 961506336), The University of Copenhagen (Grant no. 211-0357/07-3012), The Danish Ministry of Health and the Danish Environmental Protection Agency, A.P. Møller and wife Chastine McKinney Møllers foundation, and Svend Andersens Foundation. ITALIC! Finland: European Union (contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT- 2002-00603 and most recently FP7/2008-2012, DEER Grant agreement no. 212844), The Academy of Finland, Turku University Hospital Funds, Sigrid Juselius Foundation. ITALIC! Estonia, Latvia and Lithuania: European Union (QLRT-2001-02911), the Estonian Science Foundation, grant number 2991, Lithuanian Foundation for Research, Organon Agencies B.V. and the Danish Research Council, grant no. 9700833. ITALIC! Germany: European Union (contract numbers QLK4-CT-2002-00603). ITALIC! Spain: European Commission QLK4-1999-01422. M.F. received support from the Spanish Ministry of Science and Innovation (Program Ramon y Cajal). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. None of the authors have any competing interests to declare.

Reliability and validity of the Danish version of the Schema Mode Inventory (SMI).

Schema modes are conceptualized as different parts of oneself, related to specific emotions, cognitions, and behaviors. They are a central concept in schema therapy for personality pathology and other chronic psychiatric disorders. Prior research confirms the factorial validity of the Schema Mode Inventory (SMI), an instrument to assess schema modes. This study presents an evaluation of the Danish version of the SMI, including reliability and validity analyses. Psychometric properties, such as factor structure, internal reliability, as well as intercorrelations between subscales were assessed. This was done on the basis of a mixed Danish sample (N = 657; M age = 29.32 years; range = 18-66 years; 78.5% females) composed of 266 clinical and 391 nonclinical adult participants. Results indicated model fit for the 14-factor structure of the SMI and adequate to excellent internal reliabilities of the 14 subscales (Cronbach's α =.74-.96). Furthermore, the SMI scales differentiated between clinical and nonclinical participants as theoretically predicted. These findings imply that the SMI is a sound instrument to measure the schema mode model in a Danish setting, both for clinical and research purposes, and in particular for assessment prior to schema therapy.

Stressing academia? Stress-as-offence-to-self at Danish universities

ABSTRACTAcademic work has traditionally been seen as relatively stress free. However, a growing number of studies have reported increases in occupational stress experienced by university researchers. In order to explain stress among this group, we build on a new perspective in occupational stress research: the so-called stress-as-offence-to-self perspective. In line with this perspective, we have investigated the incongruence between the researchers’ work values and their perceptions of the working conditions provided by the organisation. The analysis is based on a sample of 2127 Danish university researchers. The results show that person-organisation incongruence with regard to freedom and independence in the job, job security, personal and professional development at work, and receiving peer recognition are associated with higher levels of stress among the researchers. Based on these results, we suggest three strategies for managers at universities to mitigate stress among academic employees: a tough recruitment process, a team-based organisation and a proactive human resource strategy.

Prostitution Research in Norway: Neo-liberal Discourses?

Danish prostitution research and its role in current prostitution debates in Denmark are critically addressed in NORA by Christel Stormhoj, Bodil Maria Pedersen, Inge Biehl Henningsen, Kirsten Gron...

Sponge-collecting from a drifting ice floe: the Porifera obtained in the Kara Sea by the Dutch Polar Expedition 1882-83

Sponges from the Kara Sea (Arctic Russia) collected by the Dutch Polar Expedition 1882-83 are identified and discussed. The expedition experienced an unfortunate course of events, as the research vessel RV ’Varna’ was ice-bound and eventually got crushed by ice, leaving the crew and the scientists stranded on an ice floe drifting around in the Kara Sea. The scientists still managed to do many observations and made collections of bottom animals lowering collecting gear through a hole in the ice. After being enclosed for more than a year in the ice, the men travelled in small boats and sledges to the mainland of Russia and from there returned home. The zoological collections were brought to Copenhagen by the Danish research vessel RV ‘Dijmphna’, from where the material was picked up by the Dutch scientists. Most animal groups were subsequently discussed in a series of papers published in the Bijdragen tot de Dierkunde volume 14 (1887). The sponges of the Dutch Polar Expedition were in a rather bad condition when they arrived in Amsterdam and possibly for that reason were largely ignored. They nevertheless appear to be interesting and are here presented as a belated contribution to the 1887 issue, including the description of a species new to science, Lycopodina ruijsi sp. nov. The results are discussed in the framework of our present knowledge of the sponge fauna of the Kara Sea. In Appendix ten already known species are briefly described and SEM images of their spicules provided as a contribution to Kara Sea sponge morphology,

Notes on Contributors

Notes on Contributors

Abstract C10: Quantitative proteomics of formalin-fixed paraffin-embedded, primary triple-negative breast cancer tissues of patients who experienced distant metastasis or no recurrence

Abstract Triple-negative breast cancer (TNBC) represents a major subtype of breast cancer (BC) and no biomarkers or targeted treatments are available. Retrospective proteomic analysis of formalin-fixed paraffin-embedded (FFPE) BC tissue has the potential to identify novel biomarkers and pathways associated with disease recurrence in TNBC, since sample data can be coupled with clinical data, including treatment and patient outcome. Primary TNBC tissue of patients who experienced distant metastasis or no recurrence within a 10 year follow-up period was retrieved to investigate whether proteomics using liquid chromatography tandem mass spectrometry (LC-MS/MS) can identify proteins and pathways associated with their metastatic potential. FFPE material on PEN-membrane slides were deparaffinized according to standard procedure with xylene/ethanol and stained with hematoxylin and eosin. Cancer cells were dissected by UV laser capture microdissection (LCM) and subjected to protein extraction in triethylammonium bicarbonate/acetonitrile buffer by heat-induced antigen retrieval. Extracted proteins were trypsinized and generated peptides were isobarically labelled with 6-plex tandem mass tags, combined 1:1 and subjected to hydrophilic interaction liquid chromatography LC-MS/MS. Preliminary experiments identified >500 unique proteins from BC FFPE tissue, verifying a robust setup. Cancer cells from primary TNBC FFPE tissues of 15 patients who experienced distant metastatic and 20 patients who did not have recurrence within ten years were isolated by UV-LCM and analyzed according to the above setup. The patients were stratified into four working groups based upon their menopausal status (pre or post) and their recurrence (recurrence or no-recurrence) outcome. The median aged varied from 42.2 to 63.4 years between the four groups with most tumors being diagnosed as T1 or T2 (TNM classification system). All tumors were grade 2 or higher at diagnosis, with no distant metastasis present prior to removal of the primary tumor. We identified 2564 high-confident proteins across the 35 patient samples with ≥2 unique peptides. Statistical analysis was done in RStudio and GproX and revealed distinct molecular profiles capable of separating metastatic from non-metastatic patients with a p-value ≤0.05. Furthermore three proteins were found to be differentially regulated between the two groups with a p-value <0.001 making these highly interesting targets in the prevention of metastatic lesions in TNBC. Research funded by the Danish Research Council, the A.P. Møller foundation and The Regional Strategically Research Council of Southern Denmark Citation Format: Martin H. Pedersen, Brian L. Hood, Thomas P. Conrads, Henrik J. Ditzel, Rikke Leth-Larsen. Quantitative proteomics of formalin-fixed paraffin-embedded, primary triple-negative breast cancer tissues of patients who experienced distant metastasis or no recurrence. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C10.

Is heat pain detection threshold associated with the area of secondary hyperalgesia following brief thermal sensitization? A study of healthy volunteers - design and detailed plan of analysis.

BackgroundSeveral factors are believed to influence the development and experience of pain.Human clinical pain models are central tools, in the investigation of basic physiologic pain responses, and can be applied in patients as well as in healthy volunteers. Each clinical pain model investigates different aspects of the human pain response.Brief thermal sensitization induces a mild burn injury, resulting in development of primary hyperalgesia at the site of stimulation, and secondary hyperalgesia surrounding the site of stimulation. Central sensitization is believed to play an important role in the development of secondary hyperalgesia; however, a possible association of secondary hyperalgesia following brief thermal sensitization and other heat pain models remains unknown. Our aim with this study is to investigate how close the heat pain detection threshold is associated with the size of the area of secondary hyperalgesia induced by the clinical heat pain model: Brief thermal sensitization.Methods and designWe aim to include 120 healthy participants. The participants will be tested on two separate study days with the following procedures: i) Brief thermal sensitization, ii) heat pain detection threshold and iii) pain during thermal stimulation. Additionally, the participants will be tested with the Pain Catastrophizing Scale and Hospital Anxiety and Depression Scale questionnaires.We conducted statistical simulations based on data from our previous study, to estimate an empirical power of 99.9 % with α of 0.05. We define that an R2 < 0.25 and predictive intervals larger than +/−150 cm2 are indications of a weak association.DiscussionThe area of secondary hyperalgesia may serve as a quantitative measure of the central sensitization induced by cutaneous heat stimulation, and thus may be a biomarker of an individual’s pain sensitivity. The number of studies investigating secondary hyperalgesia is growing; however basic knowledge of the physiologic aspects of secondary hyperalgesia in humans is still incomplete. We therefore find it interesting to investigate if HPDT, a known quantitative sensory test, is associated with areas of secondary hyperalgesia following brief thermal sensitizationTrial registrationClinicaltrials.gov (Identifier: NCT02527395). Danish Research Ethics Committee (Identifier: H-8-2014-012). Danish Data Protection Agency (Identifier: 30-1436).Electronic supplementary materialThe online version of this article (doi:10.1186/s12871-016-0193-2) contains supplementary material, which is available to authorized users.

Psychotropic Medications May Increase Risk of Death

Risk of death is increased in patients taking benzodiazepines, antidepressants, and antipsychotics regardless of whether or not they have dementia, according to a report by Danish researchers published in European Neuropsychopharmacology. The findings — from one of the largest ever studies of use of the drugs in individuals with dementia and matched controls — suggest a need for caution when prescribing these types of medication to the elderly. The population-based register study included 26,821 adults with a diagnosis of dementia between 1997 and 2009 and 44,286 controls with a minimum follow-up of 4 years, who were matched for age, gender, marital status, and community location [Eur Neuropsychopharmacol doi.org/10.1016/j.euroneuro.2015.08.014]. Data on the participants were taken from the Danish National Patient Registry; data on use of psychotropic medications were taken from the Danish Medicinal Product Statistics. Complete data were available for more than 99% of the patients and controls, who were traced retrospectively and prospectively for up to 12 years in the databases. The medications included in the analysis were selective serotonin reuptake inhibitors, serotonin-noradrenaline re-uptake inhibitors, tricyclic antidepressants, benzodiazepines, benzodiazepine-like drugs, first-generation antipsychotics, and second-generation anti-psychotics. Participants were considered to have taken antipsychotic medication if they received at least three prescriptions with a coverage rate of a least 60% in the 12 months before the index date. Patients in the control group had received no prescriptions for psychotropic drugs in the 12 months pre- or post-incident. Looking at survival in the year after a dementia diagnosis, Poul Jennum, MD, DSc, and colleagues found a statistically significant association between use of psychotropic medication and death, which was significantly more pronounced in controls than in patients with dementia. Use of the drugs by individuals without dementia, the authors said, might indicate they had mental health disorders with an intrinsically higher risk of death than the non-medicated patients in the control group. “We found that use of psychotropic drugs was associated with increased all-cause mortality in both patients with dementia and control subjects,” Dr. Jennum and colleagues said. “Thus, the frequently reported increased mortality with antipsychotic drugs in dementia was not restricted to subjects with impaired cognition and was not restricted to only one class of psychotropic drugs.” Examining the reasons for the increased risk of death associated with psychotropic drugs, the authors postulated that a number of factors may be at play. The medications may affect arousals from sleep as well as metabolic, respiratory, autonomic, and cardiac functions, as previously suggested by reports about benzodiazepine's impact on respiration and clonazepam's potential to induce sleep apnea. Limitations of the study cited by the researchers include lack of information about the manner and cause of death of the participants and the possibility that many of the patients in the control group may have been suffering from mental illness; lack of information about confounder variables, making it impossible to relate the findings to disease severity; and the likelihood that some patients in the control group may have had as-yet-undiagnosed dementia. “There are several questions that should be addressed in future studies, including duration and dose of treatment, subgroup analysis on specific co-morbidities, and manner and cause of death,” Dr. Jennum and colleagues wrote. The study authors reported no conflicts of interest. Judith M. Orvos, ELS, is a freelance medical writer and president of Orvos Communications in Washington, DC.

How to evaluate telemedicine projects in clinical practice?

Purpose: Based on several studies [1, 2] questioning the usefulness of randomized controlled trial as evaluation method for innovative telemedicine projects, the objective of the study was to identify what alternative type of strategy there may be suitable for evaluating an innovative telemedicine project aiming for sustainable use in complex and heterogeneous healthcare work practices. Context: The study was based on the evaluation of a Danish research project, evaluating various cross-sectoral collaboration forms for treatment of elderly acute ill medical patients. Instead of being admitted to the hospital the patients were treated at home or at an acute unit in a care centre. The primary outcome was the number of admissions within 7 days, depending on whether a medical specialist (intervention) or the general practitioners were responsible for the treatment. One of the treatment offers included that the municipal nurses had access to three telemedicine solutions; I) Sharing of telemonitored vital values between municipal nurses and a medical specialist; II) Video conferencing between municipal nurses and a medical specialist and; III) A hotline directly to the medical specialist. As the project developed, a gap between initial expectations and actual outcome appeared. This resulted in change of evaluation approach for the telemedicine intervention. Methods: The telemedicine evaluation was carried through a narrative process analysis approach, where information system development was viewed as situated socio-technical change [3]. Data was collected through participant-observation, by reviewing relevant project documents and from qualitative semi-structured interviews. 11 informants in total were interviewed including users of the technology, project managers and the supplier of the technology.