Secretion of glucagon, GLP-1 and GIP may be affected by circadian rhythm in healthy males.

BACKGROUND: Glucagon is secreted from pancreatic alpha cells in response to low blood glucose and increases hepatic glucose production. Furthermore, glucagon enhances hepatic protein and lipid metabolism during a mixed meal. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from gut endocrine cells during meals and control glucose homeostasis by potentiating insulin secretion and inhibiting food intake. Both glucose homeostasis and food intake have been reported to be affected by circadian rhythms and vice versa. In this study, we investigated whether the secretion of glucagon, GLP-1 and GIP was affected by circadian rhythms. METHODS: A total of 24 healthy men with regular sleep schedules were examined for 24 h at the hospital ward with 15 h of wakefulness and 9 h of sleep. Food intake was standardized, and blood samples were obtained every third hour. Plasma concentrations of glucagon, GLP-1 and GIP were measured, and data were analyzed by rhythmometric statistical methods. Available data on plasma glucose and plasma C-peptide were also included. RESULTS: Plasma concentrations of glucagon, GLP-1, GIP, C-peptide and glucose fluctuated with a diurnal 24-h rhythm, with the highest levels during the day and the lowest levels during the night: glucagon (p < 0.0001, peak time 18:26 h), GLP-1 (p < 0.0001, peak time 17:28 h), GIP (p < 0.0001, peak time 18:01 h), C-peptide (p < 0.0001, peak time 17.59 h), and glucose (p < 0.0001, peak time 23:26 h). As expected, we found significant correlations between plasma concentrations of C-peptide and GLP-1 and GIP but did not find correlations between glucose concentrations and concentrations of glucagon, GLP-1 and GIP. CONCLUSIONS: Our results demonstrate that under meal conditions that are similar to that of many free-living individuals, plasma concentrations of glucagon, GLP-1 and GIP were observed to be higher during daytime and evening than overnight. These findings underpin disturbed circadian rhythm as a potential risk factor for diabetes and obesity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06166368. Registered 12 December 2023.

Measurement of plasma total calcium before plasma free ionized calcium - a possibility with affordable pitfalls.

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.

Comparison Between Burden of Care Partners of Individuals with Alzheimer's Disease Versus Individuals with Other Chronic Diseases.

BACKGROUND: Caregiving in Alzheimer's disease (AD) is often provided by informal care partners, who spend more hours per week on average than care partners of individuals with conditions other than AD. However, the burden of care in partners of individuals with AD has not been systematically compared to that of other chronic diseases. OBJECTIVE: The current study therefore aims to compare the care partner burden of AD to that of other chronic diseases through a systematic literature review. METHODS: Data was collected from journal articles published in the last 10 years, using two unique search strings in PubMed and analysed using pre-defined patient-reported outcome measures (PROMs) including the EQ-5D-5L, GAD-7, GHQ-12, PHQ-9, WPAI and the ZBI. The data was grouped according to the included PROMs and the diseases studied. The number of participants in the studies reporting burden of caregiving in AD was adjusted to reflect the number of participants in studies reporting care partner burden in other chronic diseases. RESULTS: All results in this study are reported as a mean value and standard deviation (SD). The ZBI measurement was the most frequently used PROM to collect care partner burden (15 studies) and showed a moderate burden (mean 36.80, SD 18.35) on care partners of individuals with AD, higher than most of the other included diseases except for those characterized by psychiatric symptoms (mean scores 55.92 and 59.11). Other PROMs such as PHQ-9 (six studies) and GHQ-12 (four studies) showed a greater burden on care partners of individuals with other chronic diseases such as heart failure, haematopoietic cell transplantations, cancer and depression compared to AD. Likewise, GAD-7 and EQ-5D-5L measurements showed a lesser burden on care partners of individuals with AD compared to care partners of individuals with anxiety, cancer, asthma and chronic obstructive pulmonary disease. The current study suggests that care partners of individuals with AD experience a moderate burden, but with some variations depending on the PROMs used. CONCLUSION: The results of this study were mixed with some PROMs indicating a greater burden for care partners of individuals with AD versus other chronic diseases, and other PROMs showing a greater burden for care partners of individuals with other chronic diseases. Psychiatric disorders imposed a greater burden on care partners compared to AD, while somatic diseases in the musculoskeletal system resulted in a significantly smaller burden on care partners compared to AD.

Factors associated with statin discontinuation near end of life in a Danish primary health care cohort.

BACKGROUND: Long-term preventive treatment such as treatment with statins should be reassessed among patients approaching end of life. The aim of the study was to describe the rate of discontinuation of statin treatment and factors associated with discontinuation in the 6 months before death. METHODS: This study is a retrospective cohort study using national registers and blood test results from primary health care patients. Patients in the Copenhagen municipality, Denmark who died between 1997 and 2018 and were statin users during the 10-year period before death were included. We calculated the proportion who remained statin users in the 6-month period before death. Factors associated with discontinuation were tested using logistic regression. RESULTS: A total of 55,591 decedents were included. More patients continued treatment (64%, n = 35,693) than discontinued (36%, n = 19,898) the last 6 months of life. The 70 and 80 age groups had the lowest odds of discontinuing compared to the 90 (OR 1.59, 95% CI 0.93-2.72) and 100 (OR 3.11, 95% CI 2.79-3.47) age groups. Increasing comorbidity score (OR 0.89, 95% CI 0.87; 0.90 per 1-point increase) and use of statins for secondary prevention (OR 0.89, 95% CI 0.85; 0.93) reduced the likelihood of discontinuation as did a diagnosis of dementia, heart failure, or cancer. CONCLUSION: A substantial portion of patients continued statin treatment near end of life. Efforts to promote rational statin use and discontinuation are required among patients with limited life expectancy, including establishing clear, practical recommendations about statin discontinuation, and initiatives to translate recommendations into clinical practice.

Hypoalbuminemia is associated with 30-day mortality in hip fracture patients independently of Body Mass Index.

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.

Association of ferritin and transferrin saturation with all-cause mortality, and the effect of concurrent inflammation: a danish cohort study.

The association between ferritin and transferrin saturation (TS), respectively, and all-cause mortality is unclear. Furthermore, the influence of concurrent inflammation has not been sufficiently elucidated. We investigated these associations and the effect of concurrently elevated C-reactive protein (CRP), and accordingly report the levels associated with lowest all-cause mortality for females and males with and without inflammation.Blood test results from 161,921 individuals were included. Statistical analyses were performed in sex-stratified subpopulations, with ferritin or TS level as continuous exposure variables, and were adjusted for age, co-morbidity and inflammation status using CRP. An interaction was used to investigate whether the effect of ferritin or TS on all-cause mortality was modified by inflammation status (CRP ≥ 10 mg/L or CRP < 10 mg/L). Low and high ferritin and TS levels were respectively associated with increased all-cause mortality in females and in males. These associations persisted with concurrent CRP ≥ 10 mg/L. The ferritin level associated with lowest mortality was 60 µg/L for females and 125 µg/L for males with CRP < 10 mg/L. It was 52 µg/L for females and 118 µg/L for males with CRP ≥ 10 mg/L. The TS level associated with lowest mortality was 33.9% for females and 32.3% for males with CRP < 10 mg/L. It was 28.7% for females and 30.6% for males with CRP ≥ 10 mg/L.Our findings can nuance clinical interpretation and further aid in defining recommended ranges for ferritin and TS.

Glucometabolic changes influence hospitalization and outcome in patients with COVID-19: An observational cohort study.

AIMS: The aim was to report the prevalence of diabetes status in patients hospitalized with COVID-19 and assess the association between the glucometabolic status at admission and 90-day mortality. METHODS: Consecutive patients hospitalized with COVID-19 were included in the study. All participants included had an HbA1c measurement 60 days prior to or within 7 days after admission. We studied the association between diabetes status, the glycemic gap (difference between admission and habitual status), admission plasma-glucose, and mortality using Cox proportional hazards regression. RESULTS: Of 674 patients included, 114 (17%) had normal glucose level, 287 (43%) had pre-diabetes, 74 (11%) had new-onset, and 199 (30%) had diagnosed diabetes. No association between diabetes status, plasma-glucose at admission, and mortality was found. Compared to the 2nd quartile (reference) of glycemic-gap, those with the highest glycemic gap had increased mortality (3rd (HR 2.38 [1.29-4.38], p = 0.005) and 4th quartile (HR 2.48 [1.37-4.52], p = 0.002). CONCLUSION: Abnormal glucose metabolism was highly prevalent among patients hospitalized with COVID-19. Diabetes status per se or admission plasma-glucose was not associated with a poorer outcome. However, a high glycemic gap was associated with increased risk of mortality, suggesting that, irrespective of diabetes status, glycemic stress serves as an important prognostic marker for mortality.

The 10 most frequently requested blood tests in the Capital Region of Denmark, 2010-2019 and simulated effect of minimal retesting intervals.

As healthcare costs continue to rise throughout the world, critical assessment of the appropriateness of expenses gain focus. OBJECTIVES: We aimed to describe the developments in test numbers of the 10 most frequently requested tests, and to simulate the effect of introducing minimal retesting intervals. DESIGN & METHODS: Data from the blood tests - albumin, alanine transaminase, cholesterol, creatinine, C-reactive protein, hemoglobin, hemoglobin A1c, potassium, sodium, and thyrotropin - from 2,687,589 patients handled by the Capital Region of Denmark from 2010 to 2019 was used. Tallies of each test per year were graphed. A simulation of the effect of minimal retesting intervals on test count and blood sampling volume was performed by virtually removing requests made prior to a set of possible minimal retesting intervals. RESULTS: Increases in requests were observed both from hospitals and general practitioners. The number of requests for hemoglobin A1c increased more than the other tests. The increases could not be accounted for by an increase in population size and aging of the population, and therefore suggests possible inappropriate increase in monitoring of patients. The simulated effect of applying minimal retesting intervals showed large reductions in tests and blood sampled. CONCLUSIONS: For hospitals, the simulation suggested that applying minimal retesting intervals could lead to significant reductions in both the number of blood tests performed and in the amount of blood drawn for testing. For general practitioners, the simulation showed only minimal reductions in number of tests and blood volume drawn.

Decreased plasma lipid levels in a statin-free Danish primary health care cohort between 2001 and 2018.

BACKGROUND: Lipid levels in blood have decreased considerably during the past decades in the general population partly due to use of statins. This study aims to investigate the trends in lipid levels between 2001 and 2018 in a statin-free population from primary health care, overall and by sex and age. METHODS: In a cohort of 634,119 patients from general practice with no diagnoses or medical treatments that affected lipid levels of total cholesterol (TC; n = 1,574,339) between 2001 and 2018 were identified. Similarly, measurements of low-density lipoprotein cholesterol (LDL-C; n = 1,302,440), high-density lipoprotein cholesterol (HDL-C; n = 1,417,857) and triglycerides (TG; n = 1,329,477) were identified. RESULTS: Mean TC decreased from 5.64 mmol/L (95% CI: 5.63-5.65) in 2001 to 5.17 mmol/L (95% CI: 5.16-5.17) in 2018 while LDL-C decreased from 3.67 mmol/L (95% CI: 3.66-3.68) to 3.04 mmol/L (95% CI: 3.03-3.04). Women aged 70-74 years experienced the largest decreases in TC levels corresponding to a decrease of 0.7 mmol/L. The decrease in LDL-C levels was most pronounced in men ≥85 years with a decrease of 0.9 mmol/L. For both genders, TC and LDL-C levels increased with advancing age until around age 50. After menopause the women had higher TC and LDL-C levels than the men. The median (geometric mean) TG level decreased by 0.4 mmol/L from 2001 to 2008, after which it increased slightly by 0.1 mmol/L until 2018. During life the TG levels of the men were markedly higher than the women's until around age 65-70. HDL-C levels showed no trend during the study period. CONCLUSIONS: The levels of TC and LDL-C decreased considerably in a statin-free population from primary health care from 2001 to 2018. These decreases were most pronounced in the elderly population and this trend is not decelerating. For TG, levels have started to increase, after an initial decrease.

The Circadian Clock Is Sustained in the Thyroid Gland of VIP Receptor 2 Deficient Mice.

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 conclusion, sustained and identical rhythms (phases and amplitudes) of three clock genes were found in VPAC2 deficient mice during LD and DD suggesting high degree of independence of the thyroid clock from the master SCN clock.

Thyroid-stimulating hormone (TSH) is associated with 30-day mortality in hip fracture patients.

PURPOSE: The aim of this study is to assess the possible association between thyroid-stimulating hormone (TSH) and mortality in hip fracture patients. PATIENTS AND METHODS: The study is based on a hip fracture database from Bispebjerg University Hospital (Copenhagen, Denmark). This database includes all hip fracture patients (ICD-10 codes DS720 (femoral neck), DS721 (pertrochanteric), and DS722 (subtrochanteric)) admitted to Bispebjerg Hospital from 1996 to 2012. From this database, we identified all surgically treated hip fracture patients aged > 60 years with available plasma TSH-measurements at admission. RESULTS: Of the 914 included patients (24% men and 76% women), 10.5% died within 30 days. At inclusion, 161 (17.6%) of the patients were hyperthyroid (TSH < 0.65 mIU/L), 58 (6.4%) were hypothyroid (TSH > 4.8 mIU/L), while 695 (76.0%) were euthyroid (0.65 < TSH < 4.80 mIU/L), p = 0.03. Mortality was significantly higher in the two higher quartiles of TSH [Q3 (13.0%) and Q4 (15.4%)] compared to the two lower quartiles [Q1 (7.4%) and Q2 (6.2%), p = 0.0003. After adjustment for age, sex and Charlson Comorbidity Index (CCI) in a Cox proportional hazard model, the risk of 30-day mortality continued to be increased in patients with TSH above the median as compared to patients with TSH below the median (HR 2.1 (1.4-3.3), p = 0.0006]. CONCLUSION: The study demonstrates increased 30-day mortality in surgically treated hip fracture patients with plasma TSH levels above the median (1.41 mIU/L) at admission, even after adjusting for age, sex and CCI.

Circadian variations in plasma concentrations of cholecystokinin and gastrin in man.

Cholecystokinin (CCK) is a gut hormone which regulates gallbladder contraction and pancreatic enzyme secretion. In addition, CCK is also a major intestinal satiety signal. The knowledge about CCK in circulation, however, has been limited by difficulties in accurate measurement of the concentrations in plasma. Thus, CCK circulates in low concentrations and furthermore, it is structurally homologous to the antral hormone, gastrin, which circulates in higher concentrations. Therefore, most antibodies raised against CCK cross-react in immunoassays with gastrin. However, using highly sensitive and entirely specific in-house radioimmunoassays, which meet these challenges, we have now measured the daily concentration-variations of CCK and gastrin in plasma from young healthy men (n = 24). Plasma was sampled every third hour from each person during 24 h. The results show that the gastrointestinal secretion of both CCK and gastrin in man display significant circadian variations.

A compulsory pop-up form reduces the number of vitamin D requests from general practitioners by 25 percent.

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.

Fetal fraction of cell-free DNA in pregnancies after fresh or frozen embryo transfer following assisted reproductive technologies.

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 at Copenhagen University Hospital Hvidovre. The NIPT-test was performed by massive-parallel whole-genome sequencing. The FF was determined using the SeqFF algorithm. MAIN RESULTS AND THE ROLE OF CHANCE: We found a reduction in FF in ART patients compared with naturally conceived pregnancies, and the reduction was more pronounced for ART pregnancies after fresh ET (mean FF = 0.049) compared with frozen ET (mean FF = 0.063) (multivariate analysis adjusted for maternal BMI, P = 0.02). Another multivariate analysis, adjusted for BMI and multiples of median (MoM) values for pregnancy-associated plasma protein-A (PAPP-A), demonstrated a significantly reduced FF for ART pregnancies (mean FF = 0.056) compared with naturally conceived pregnancies (mean FF = 0.072) (P < 0.0001). We found that FF was significantly reduced with increasing maternal BMI (P < 0.0001) and with decreasing MoM values of PAPP-A (P = 0.003). LIMITATIONS, REASONS FOR CAUTION: A limitation of our study design was the relatively small sample size. Another limitation was that the control group was not matched with the ART-treated women. The majority of the women from the control group had a high risk from cFTS, thereby their biochemical markers were diverging. However, the biochemical markers for the ART-treated women with fresh or frozen ET were not divergent within the subgroups. WIDER IMPLICATIONS OF THE FINDINGS: Concurrent with other studies demonstrating a reduced FF for singleton pregnancies after ART treatment compared with naturally conceived pregnancies, we found a reduction in FF between the two groups. This is one of the first studies to examine FF in ART pregnancies after fresh ET compared with frozen ET, hence the existing knowledge is limited. We find that FF is even more reduced in pregnancies following fresh ET compared with frozen ET, which might possibly reflect the predisposition of being small for gestational age after fresh ET compared with natural cycle frozen ET. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal (the A.P. Møller Foundation for General Purposes). All authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: NA.

Characteristics of patients with COVID-19 pneumonia at Hvidovre Hospital, March-April 2020.

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.

Pre-fracture medication use as a predictor of 30-day mortality in hip fracture patients: an analysis of 141,201 patients.

PURPOSE: To evaluate the predictive value of pre-fracture medication usage on 30-day mortality following a hip fracture. METHODS: Information on age, sex, fracture type, time of death and Charlson co-morbidity index (CCI) was collected from the Danish National Patient Registry on all patients above 60 years, sustaining a hip fracture during the period January 1995 to December 2013. Information on drug usage was obtained from the Danish National Prescription Database. Hazard ratios were calculated with 30-day mortality as the outcome. A univariate and 3 multivariate analyses were conducted with increasing adjustments, starting with age, sex and fracture type, adding co-morbidity and dose in the latter. RESULTS: 141,201 patients were included and a total of 12 drugs/drug groups were identified for analysis. Increased mortality was evident in all analyses for antiarrhythmics, beta blockers, proton pump inhibitors, loop diuretics, opioids, acetaminophen and for psycholeptics. For ACE-inhibitors, increased mortality was found in all analyses, except after adjustment for co-morbidity and dose. For thiazide diuretics, a significantly reduced mortality was evident in all but the univariate analyses while NSAIDs and statins were associated with a significantly reduced mortality in all analyses. For calcium channel blockers, an insignificant decrease was found after adjustment for dose. Further analysis showed a dose-response relationship for all drugs except ACE-inhibitors and calcium channel blockers. CONCLUSION: The study shows a correlation between pre-fracture usage of certain drugs and 30 day mortality after a hip fracture.

Diurnal Variation of Markers for Cholesterol Synthesis, Cholesterol Absorption, and Bile Acid Synthesis: A Systematic Review and the Bispebjerg Study of Diurnal Variations.

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.

Change in HbA1c concentration as decision parameter for frequency of HbA1c measurement.

Hemoglobin A1c (HbA1c) is a long-term measure for glucose concentration in plasma. Since its introduction as a diabetes monitoring tool, and its more recent application as a diagnostic tool, the number of measurements of HbA1c have risen dramatically. However, HbA1c change is slow, so repeating measurements should not be done too often. We use a large, unfiltered dataset from 52,017 patients to determine the possible rate of change in HbA1c concentration. In our laboratory, the critical difference between HbA1c measurements is 8.5%. Our data show that a 1-unit HbA1c rise takes 4 weeks to occur, hence, at a HbA1c concentration around 50 mmol/mol Hgb, a critically increased HbA1c concentration cannot be determined until after 16 weeks. Conversely a critically lower HbA1c can manifest itself after 2 weeks, but after 7 weeks the dropping tendency stops. The amount of measurements that can be cancelled because they were taken sooner than 16 weeks is 23 percent.

Excess mortality following hip fracture in patients with diabetes according to age: a nationwide population-based cohort study of 154,047 hip fracture patients.

OBJECTIVE: to test the hypothesis that excess mortality conferred by diabetes following hip fracture decreases with advancing age. METHODS: a nationwide population-based cohort study including 154,047 patients who were admitted with a hip fracture in Denmark from 1996 to 2012. Information on hip fracture diagnosis, diabetes, other comorbidities, and the primary outcome all-cause mortality was collected using the national Danish health registries. The association between diabetes and all-cause mortality according to age was assessed using Cox proportional hazards regression in the age categories: <50, 50-59, 60-69, 70-79, 80-89 and ≥90 years. RESULTS: during a median follow-up of 3 years (interquartile range: 1-6 years, 603,091 person-years) 114,990 died from any cause. In total, 8% (n = 12,158) of the patients had diabetes at baseline and had unadjusted, and age, sex and Charlson Comorbidity Index adjusted hazard ratios for all-cause mortality of 1.19 (95% confidence interval: 1.16-1.21) and 1.14 (1.12-1.17) as compared to patients without diabetes. The sex and Charlson Comorbidity Index adjusted hazard ratios according to age were 1.64 (1.34-2.02) for patients <50 years, 1.26 (1.12-1.40) for patients 50-59 years, 1.21 (1.13-1.29) for patients 60-69 years, 1.11 (1.07-1.16) for patients 70-79 years, 1.10 (1.07-1.14) for patients 80-89 years and 1.09 (1.02-1.16) for patients ≥90 years. There was a statistically significant interaction between diabetes and age (P < 0.001). CONCLUSIONS: diabetes is associated with excess mortality following hip fracture across all ages, but the excess mortality decreases with advancing age.