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Free ionized calcium (fCa) is considered the gold standard for assessing calcium status in patients, but it is relatively expensive and is associated with several preanalytical and analytical error sources. We investigated the feasibility of using a reflex test that involves first measuring total calcium (tCa) and if out of reference range, then measure fCa, with expectation of reducing the number of fCa measurements. We used data from 1815 unique patients with concurrent measurement of fCa, tCa and albumin adjusted calcium (aCa). Patients were stratified by albumin level, and the association of fCa to tCa and aCa respectively was assessed with linear regression. The regression analysis showed the best linearity for tCa and aCa at albumin <35 g/L (R2: 0.80–0.90), and the poorest at albumin >40 g/L (R2: tCa 0.58; aCa 0.59). We examined the accuracy of hypo- and hypercalcemia classifications for tCa, aCa and the reflex test. aCa had more misclassifications of hypo- and hypercalcemia than tCa, with respectively 25% and 21%. Implementation of the reflex test would correct any false hypo- or hypercalcemia classified by tCa, leaving only false negative results corresponding to 9% of all tCa measurements. False negative results were on average 0.04 mmol/L above or below the reference range of fCa. Implementation of the reflex test reduces the number of fCa by 68% without major errors diagnosing hyper- or hypocalcemia. Keywords: Endocrinologylaboratory managementlaboratory routines and automationlaboratory screeningmedical biochemistrybone metabolism, Free ionized calcium (fCa) is considered the gold standard for assessing calcium status in patients, but it is relatively expensive and is associated with several preanalytical and analytical error sources. We investigated the feasibility of using a reflex test that involves first measuring total calcium (tCa) and if out of reference range, then measure fCa, with expectation of reducing the number of fCa measurements. We used data from 1815 unique patients with concurrent measurement of fCa, tCa and albumin adjusted calcium (aCa). Patients were stratified by albumin level, and the association of fCa to tCa and aCa respectively was assessed with linear regression. The regression analysis showed the best linearity for tCa and aCa at albumin <35 g/L (R2: 0.80–0.90), and the poorest at albumin >40 g/L (R2: tCa 0.58; aCa 0.59). We examined the accuracy of hypo- and hypercalcemia classifications for tCa, aCa and the reflex test. aCa had more misclassifications of hypo- and hypercalcemia than tCa, with respectively 25% and 21%. Implementation of the reflex test would correct any false hypo- or hypercalcemia classified by tCa, leaving only false negative results corresponding to 9% of all tCa measurements. False negative results were on average 0.04 mmol/L above or below the reference range of fCa. Implementation of the reflex test reduces the number of fCa by 68% without major errors diagnosing hyper- or hypocalcemia.

The aim of this study was to assess the possible association between P-Albumin and 30-day mortality in hip fracture patients. The study is based on information from a database of hip fracture patients, established and collected at Bispebjerg University Hospital (Copenhagen, Denmark). This database includes all femoral neck (DS720), pertrochanteric (DS721) and subtrochanteric fractures (DS722) admitted to Bispebjerg Hospital between 1996 and 2012. We further identified all surgically treated hip fracture patients aged >60 years with an available P-Albumin at admission. 1856 patients were eligible for inclusion in this study (73.7% female, 26.3% male). 11.8% of these had died within 30 days. Differences between continuous variables were tested using unpaired t-tests while differences in the distribution of categorical variables were tested using chi square tests. After adjusting for co-variates in a logistic regression model, the association between P-Albumin and 30-day mortality remained increased, (OR 1.09, 95% CI 1.05;1.11 (p < 0.0001)). This study shows an increased 30-day mortality risk among surgically treated hip fracture patients with decreasing levels of P-Albumin even after adjusting for age, sex, BMI, CCI and fracture type. Routine screening of patients for hypoalbuminemia at hospital admission may be beneficial in the management of hip fracture patients.

VIP/VPAC2-receptor signaling is crucial for functioning of the circadian clock in the suprachiasmatic nucleus (SCN) since the lack results in disrupted synchrony between SCN cells and altered locomotor activity, body temperature, hormone secretion and heart rhythm. Endocrine glands, including the thyroid, show daily oscillations in clock gene expression and hormone secretion, and SCN projections target neurosecretory hypothalamic thyroid-stimulating hormone (TSH)-releasing hormone cells. The aim of the study was to gain knowledge of mechanisms important for regulation of the thyroid clock by evaluating the impact of VIP/VPAC2-receptor signaling. Quantifications of mRNAs of three clock genes (Per1, Per2 and Bmal1) in thyroids of wild type (WT) and VPAC2-receptor deficient mice were done by qPCR. Tissues were taken every 4th h during 24-h 12:12 light-dark (LD) and constant darkness (DD) periods, both genders were used. PER1 immunoreactivity was visualized on sections of both WT and VPAC2 lacking mice during a LD cycle. Finally, TSH and the thyroid hormone T4 levels were measured in the sera by commercial ELISAs. During LD, rhythmic expression of all three mRNA was found in both the WT and knockout animals. In VPAC2-receptor knockout animals, the amplitudes were approximately halved compared to the ones in the WT mice. In the WT, Per1 mRNA peaked around “sunset”, Per2 mRNA followed with approximately 2 h, while Bmal1 mRNA was in antiphase with Per1. In the VPAC2 knockout mice, the phases of the mRNAs were advanced approximately 5 h compared to the WT. During DD, the phases of all the mRNAs were identical to the ones found during LD in both groups of mice. PER1 immunoreactivity was delayed compared to its mRNA and peaked during the night in follicular cells of both the thyroid and parathyroid glands in the WT animals. In WT animals, TSH was high around the transition to darkness compared to light-on, while T4 did not change during the 24 h cycle. In conclu

INTRODUCTION: The first case of coronavirus disease 2019 (COVID-19) disease caused by severe acute respiratory syndrome coronavirus-2 occurred in Denmark on 27 February 2020. On 10 March, the first case of COVID-19 pneumonia was admitted to Hvidovre Hospital.METHODS: Retrospective case review of individuals 18 years or older who were admitted consecutively to Hvidovre Hospital from 10 March through 23 April 2020.RESULTS: A total of 175 individuals were admitted with COVID-19 pneumonia. The median age was 71 years, 48.6% were male and 71% had at least one co-morbidity. The most commonly presenting symptoms were dyspnoea, dry cough, and fever. The majority of patients had lymphopenia, elevated liver function tests and C-reactive protein. Nearly two in three presented with multilobar infiltration by chest X-ray. Respiratory failure leading to invasive mechanical ventilation developed in 27 patients (15.4%). By 20 April, 23 of 175 (13.1%) patients remained hospitalised, 43 (24.6%) had died and 109 (62.3%) had been discharged.CONCLUSIONS: The manifestations of COVID-19 at presentation were similar to those seen in other reports. Our population was older, slightly overrepresented by women and had a high level of co-morbidity. COVID-19 admittance was associated with frequent need of intensive care and mechanical ventilation that was associated with a very high mortality.FUNDING: none.TRIAL REGISTRATION: not relevant.

Objective: Healthcare costs, including costs for laboratory tests, are increasing worldwide. One example is the measurement of vitamin D. General practitioners in the Capital Region of Denmark include a vitamin D status in approximately 20% of all laboratory requisitions. This study intended to examine the effect of a compulsory pop-up form in the electronic request system on the number of vitamin D tests and to monitor the indications. Design: From 1 January 2017, we introduced a compulsory pop-up form in which the general practitioners had to state the indication for measuring vitamin D, choosing from a predefined set of indications. Intervention practitioners were compared with control practitioners before and after the intervention. Setting: General practices in the Capital Region of Denmark. Subjects: In total, 572 general practitioners and 383,964 patients were included in the period from 1 January 2016 to 31 December 2018. Main outcome measures: Number of vitamin D tests and distribution of indications. Results: We observed a drop in number of vitamin D requisitions to 70% (in 2017) and 75% (in 2018) relative to 2016. During the same period, the number of requisitions increased by 33% in a non-intervention group of practitioners. The indication ‘Monitoring of treatment with vitamin D’ was the most frequently used indication, recorded in 121,475 patients. Conclusion: A compulsory pop-up form reduces the number of vitamin D requests from general practitioners by 25%. The implication is that pop-up forms can be used to decrease healthcare costs.

STUDY QUESTION: Is the fetal fraction (FF) of circulating cell-free DNA (cfDNA) affected in pregnancies following ART treatment with either fresh or frozen embryo transfer (ET) compared with natural conception? SUMMARY ANSWER: This study shows a significant reduction in the FF in ART patients compared with naturally conceived pregnancies, which seems to be more pronounced after fresh ET compared with frozen ET. WHAT IS KNOWN ALREADY: Non-invasive prenatal testing (NIPT) is based on cfDNA in maternal blood, of which about 10% is of placental origin and thus represents the fetal karyotype. Validation studies have demonstrated a high sensitivity, specificity and positive predictive value of NIPT for the detection of fetal trisomy 21, 18 and 13. Nevertheless, the FF of cfDNA is an important factor for NIPT test accuracy. Several studies have found a reduction in FF for pregnancies following ART in comparison with natural conception. However, knowledge on how the FF is affected in ART pregnancies after fresh ET compared with frozen ET is very limited. STUDY DESIGN, SIZE, DURATION: The study was designed as a case-control study. A total of 54 women with an ongoing pregnancy following ART treatment were included. After exclusion for different reasons, statistical analyses were based on 23 NIPT samples from pregnant women treated with fresh ET and 26 NIPT samples from pregnant women treated with frozen-thawed ET in a modified natural cycle. Women were included between February 2018 and November 2018. The results were compared with a control group of 238 naturally conceived pregnancies with a high-risk result from the combined first trimester screening (cFTS). PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included women from the Fertility Clinics at Copenhagen University Hospital Hvidovre and Copenhagen University Hospital Rigshospitalet. Blood samples for NIPT analysis were drawn between 11 + 0 and 14 + 2 weeks of gestation and were all analyzed at the NIPT Center

Human studies have shown diurnal rhythms of cholesterol and bile acid synthesis, but a better understanding of the role of the circadian system in cholesterol homeostasis is needed for the development of targeted interventions to improve metabolic health. Therefore, we performed a systematic literature search on the diurnal rhythms of cholesterol synthesis and absorption markers and of bile acid synthesis markers. We also examined the diurnal rhythms of the cholesterol synthesis markers lathosterol and desmosterol, and of the cholesterol absorption markers cholestanol, campesterol, and sitosterol in serum samples from the Bispebjerg study. These samples were collected every three hours over a 24-hour period in healthy males (n = 24) who consumed low-fat meals. The systematic search identified sixteen papers that had examined the diurnal rhythms of the cholesterol synthesis markers lathosterol (n = 3), mevalonate (n = 9), squalene (n = 2), or the bile acid synthesis marker 7α-hydroxy-4-cholesten-3-one (C4) (n = 4). Results showed that lathosterol, mevalonate, and squalene had a diurnal rhythm with nocturnal peaks, while C4 had a diurnal rhythm with daytime peaks. Furthermore, cosinor analyses of the serum samples showed a significant diurnal rhythm for lathosterol (cosinor p < 0.001), but not for desmosterol, campesterol, sitosterol, and cholestanol (cosinor p > 0.05). In conclusion, cholesterol synthesis and bile acid synthesis have a diurnal rhythm, though no evidence for a diurnal rhythm of cholesterol absorption was found under highly standardised conditions. More work is needed to further explore the influence of external factors on the diurnal rhythms regulating cholesterol homeostasis.