Healthcare professionals' competencies and confidence in managing hospitalized patients with type 2 diabetes.

AIMS: In hospitals, 15%-20% of patients have diabetes. Therefore, all healthcare professionals (HCPs) must have a basic knowledge of in-hospital diabetes management. This survey assessed the knowledge of diabetes among HCPs in Denmark. METHODS: A 27-item questionnaire was developed and reviewed independently before the survey was distributed. The questionnaire contained seven baseline questions on the HCPs' current workplace, educational level, usual shift routines and years of experience, 18 multiple-choice questions and 2 cases. RESULTS: A total of 252 completed questionnaires were returned by 133 (52.8%) physicians, 101 (40.1%) nurses and 18 (7.1%) healthcare assistants. HCPs answered 50% of the questions correctly. Having experience from endocrinological departments increased the correct response score (0%-100%) by 6.2% points (95% CI 0.3-12.1) (p = 0.039) and 3.1% points (95% CI 1.5-4.7) for every increase in confidence level on a scale from 1 to 10 (p < 0.001). HCPs scored 8 out of 10 on a confidence level scale on average. In a fictive case, 50% of HCPs administered the correct bolus insulin dose. Hyperglycaemia (>10.0 mmol/L) and hypoglycaemia (<3.9 mmol/L) were correctly identified by around 40% of HCPs. Hypoglycaemia was rated more important than hyperglycaemia by most HCPs. CONCLUSION: Significant gaps in identifying hypo- and hyperglycaemia and correct administration of bolus insulin have been identified, which could be targeted in future education for HCPs. HCPs answered 50% of questions related to in-hospital diabetes management correctly. Experience from endocrinological departments and self-rated confidence levels are associated with HCPs' in-hospital diabetes competencies.

Simulation of functional additive and non-additive genetic effects using statistical estimates from quantitative genetic models.

Stochastic simulation software is commonly used to aid breeders designing cost-effective breeding programs and to validate statistical models used in genetic evaluation. An essential feature of the software is the ability to simulate populations with desired genetic and non-genetic parameters. However, this feature often fails when non-additive effects due to dominance or epistasis are modeled, as the desired properties of simulated populations are estimated from classical quantitative genetic statistical models formulated at the population level. The software simulates underlying functional effects for genotypic values at the individual level, which are not necessarily the same as effects from statistical models in which dominance and epistasis are included. This paper provides the theoretical basis and mathematical formulas for the transformation between functional and statistical effects in such simulations. The transformation is demonstrated with two statistical models analyzing individual phenotypes in a single population (common in animal breeding) and plot phenotypes of three-way hybrids involving two inbred populations (observed in some crop breeding programs). We also describe different methods for the simulation of functional effects for additive genetics, dominance, and epistasis to achieve the desired levels of variance components in classical statistical models used in quantitative genetics.

Association between recent exposure to continuous glucose monitoring-recorded hypoglycaemia and counterregulatory and symptom responses to subsequent controlled hypoglycaemia in people with type 1 diabetes.

AIM: Experimental hypoglycaemia blunts the counterregulatory hormone and symptom responses to a subsequent episode of hypoglycaemia. In this study, we aimed to assess the associations between antecedent exposure and continuous glucose monitoring (CGM)-recorded hypoglycaemia during a 1-week period and the counterregulatory responses to subsequent experimental hypoglycaemia in people with type 1 diabetes. MATERIALS AND METHODS: Forty-two people with type 1 diabetes (20 females, mean ± SD glycated haemoglobin 7.8% ± 1.0%, diabetes duration median (interquartile range) 22.0 (10.5-34.9) years, 29 CGM users, and 19 with impaired awareness of hypoglycaemia) wore an open intermittently scanned CGM for 1 week to detect hypoglycaemic exposure before a standardized hyperinsulinaemic-hypoglycaemic [2.8 ± 0.1 mmol/L (50.2 ± 2.3 mg/dl)] glucose clamp. Symptom responses and counterregulatory hormones were measured during the clamp. The study is part of the HypoRESOLVE project. RESULTS: CGM-recorded hypoglycaemia in the week before the clamp was negatively associated with adrenaline response [ß -0.09, 95% CI (-0.16, -0.02) nmol/L, p = .014], after adjusting for CGM use, awareness of hypoglycaemia, glycated haemoglobin and total daily insulin dose. This was driven by level 2 hypoglycaemia [<3.0 mmol/L (54 mg/dl)] [ß -0.21, 95% CI (-0.41, -0.01) nmol/L, p = .034]. CGM-recorded hypoglycaemia was negatively associated with total, autonomic, and neuroglycopenic symptom responses, but these associations were lost after adjusting for potential confounders. CONCLUSIONS: Recent exposure to CGM-detected hypoglycaemia was independently associated with an attenuated adrenaline response to experimental hypoglycaemia in people with type 1 diabetes.

Summary of clinical investigation plan for The DIATEC trial: in-hospital diabetes management by a diabetes team and continuous glucose monitoring or point of care glucose testing - a randomised controlled trial.

BACKGROUND: Worldwide, up to 20 % of hospitalised patients have diabetes mellitus. In-hospital dysglycaemia increases patient mortality, morbidity, and length of hospital stay. Improved in-hospital diabetes management strategies are needed. The DIATEC trial investigates the effects of an in-hospital diabetes team and operational insulin titration algorithms based on either continuous glucose monitoring (CGM) data or standard point-of-care (POC) glucose testing. METHODS: This is a two-armed, two-site, prospective randomised open-label blinded endpoint (PROBE) trial. We recruit non-critically ill hospitalised general medical and orthopaedic patients with type 2 diabetes treated with basal, prandial, and correctional insulin (N = 166). In both arms, patients are monitored by POC glucose testing and diabetes management is done by ward nurses guided by in-hospital diabetes teams. In one of the arms, patients are monitored in addition to POC glucose testing by telemetric CGM viewed by the in-hospital diabetes teams only. The in-hospital diabetes teams have operational algorithms to titrate insulin in both arms. Outcomes are in-hospital glycaemic and clinical outcomes. DISCUSSION: The DIATEC trial will show the glycaemic and clinical effects of in-hospital CGM handled by in-hospital diabetes teams with access to operational insulin titration algorithms in non-critically ill patients with type 2 diabetes. The DIATEC trial seeks to identify which hospitalised patients will benefit from CGM and in-hospital diabetes teams compared to POC glucose testing. This is essential information to optimise the use of healthcare resources before broadly implementing in-hospital CGM and diabetes teams. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov with identification number NCT05803473 on March 27th 2023.

Topoisomerase 1 inhibits MYC promoter activity by inducing G-quadruplex formation.

We have investigated the function of human topoisomerase 1 (TOP1) in regulation of G-quadruplex (G4) formation in the Pu27 region of the MYC P1 promoter. Pu27 is among the best characterized G4 forming sequences in the human genome and it is well known that promoter activity is inhibited upon G4 formation in this region. We found that TOP1 downregulation stimulated transcription from a promoter with wildtype Pu27 but not if the G4 motif in Pu27 was interrupted by mutation(s). The effect was not specific to the MYC promoter and similar results were obtained for the G4 forming promoter element WT21. The other major DNA topoisomerases with relaxation activity, topoisomerases 2α and ß, on the other hand, did not affect G4 dependent promoter activity. The cellular studies were supported by in vitro investigations demonstrating a high affinity of TOP1 for wildtype Pu27 but not for mutant sequences unable to form G4. Moreover, TOP1 was able to induce G4 formation in Pu27 inserted in double stranded plasmid DNA in vitro. This is the first time TOP1 has been demonstrated capable of inducing G4 formation in double stranded DNA and of influencing G4 formation in cells.

Effectiveness of a Preschool Motor Skill Intervention on Body Mass Index and Movement Behavior: 6-, 18-, and 30-Month Findings From a Cluster Randomized Controlled Trial.

PURPOSE: To study the effectiveness of a preschool staff-delivered motor skills intervention on body composition and physical activity over a 2.5-year time frame. METHODS: In this pragmatic parallel cluster randomized controlled trial (16 preschools), outcome data were collected after 6 (body composition only), 18, and 30 months of intervention. The main physical activity outcomes were accelerometer behavior measures summarizing the total percentage of child daily movement (walk, run, cycle, and standing that included minor movements) and preschool movement during preschool attendance. To estimate between-group mean differences in outcomes, mixed-linear regression analyses including baseline value of the selected outcome and a treatment × time interaction term as a fixed effect were applied. In addition, the baseline preschool and child were included as a random effect. RESULTS: For body mass index, a total of 437 children (90%) had at least one valid baseline and one follow-up assessment. The corresponding numbers for preschool movement and daily movement were 163 (55%) and 146 (49%), respectively. No significant between-group mean difference was identified for body mass index, waist-to-height ratio, or any physical activity outcomes. CONCLUSION: Overall, this preschool motor skills intervention had no effect on either child anthropometry or physical activity, consistent with previous studies.

Effect of insulin degludec versus insulin glargine U100 on nocturnal glycaemia assessed by plasma glucose profiles in people with type 1 diabetes prone to nocturnal severe hypoglycaemia.

AIM: To compare nocturnal glucose profiles according to hourly plasma glucose measurements during treatment with insulin degludec and insulin glargine U100 in a cohort of people with type 1 diabetes prone to nocturnal severe hypoglycaemia. MATERIALS AND METHODS: The HypoDeg trial is a 2-year investigator-initiated, randomized, controlled crossover trial in 149 participants randomized to treatment with insulin degludec and insulin glargine U100 for 12 months each. The 51 participants in this predefined substudy stayed at least one night in hospital during each treatment arm for plasma glucose samples to be taken. Endpoints were glucose profiles, including mean plasma glucose, glycaemic variability and risk of hypoglycaemia. RESULTS: There were no differences between treatments regarding mean plasma glucose. We saw a flatter glucose profile during insulin degludec compared with insulin glargine U100 treatment, which had a nadir at 4:00 AM, with a subsequent rise. During treatment with insulin degludec, the participants had lower glycaemic variability, with an estimated treatment difference of -4.3% (95% confidence interval [CI] -8.1 to -0.5; P < 0.05). Participants treated with insulin degludec were less likely to experience nocturnal hypoglycaemia below 3.0 mmol/L (hazard ratio 0.36 [95% CI 0.17-0.73; P < 0.05]). CONCLUSION: Based on nocturnal plasma glucose measurements, treatment with insulin degludec compared with insulin glargine U100 administered in the evening results in lower glycaemic variability and lower risk of nocturnal hypoglycaemia without differences in mean plasma glucose.

Recreational screen time trajectories during early childhood and imaging-measured body composition at age 7 in the Odense child cohort.

BACKGROUND: Children spend increasing amounts of time on recreational screen media, which may lead to an obesogenic environment. OBJECTIVES: We investigated the association of trajectories of screen time across ages 3, 5 and 7 years with body composition at age 7 in the Odense Child Cohort. METHODS: Data were collected in the Municipality of Odense, Denmark, between 2010 and 2019. Group-based trajectory modelling was applied to group participants into four trajectories of prospective parent-reported screen time. Body composition was assessed using dual-energy x-ray absorptiometry with calculated fat-mass index (FMI) as the primary outcome. Primary models were linear multivariable regression models adjusted for participants' sex, age, birthweight, maternal origin, maternal education, maternal body-mass-index, and maternal age. Further models were adjusted for additional possible confounders. Selection bias was addressed by inverse probability weighting. RESULTS: In total, 803 children (48.2% female) were included in the primary analysis. Participants with screen time at all time points were assigned to four trajectory groups [constant low screen time (12.7%), low increase (36.3%), high increase between ages 3 and 5 (33.5%) and high increase in screen time (17.5%)]. Sample characteristics differed across missing data status and trajectories. Mean FMI (kg/m2 ) and standard deviation (SD) were 3.7 (SD 1.3) and 3.9 (SD 1.6) for the constant low versus high screen time, respectively. No differences in FMI were found between screen time trajectory groups at age 7 (adjusted mean difference 0.1 kg/m2 , 95% confidence interval -0.3, 0.5 for constant low versus high screen time). No consistent associations between screen time groups and secondary body composition outcomes were found. CONCLUSIONS: Results from this study do not suggest that recreational screen time from age 3 to 7 years is associated with adiposity or other measures of body composition.

Recreational screen media use among Danish children aged 6-11 years: influence of parental screen media habits and attitudes.

AIMS: Little is known about the influence of parents' screen media habits and attitudes towards screen media on children's screen use. We investigated associations of parental screen use, their smartphone addiction and screen media attitudes, with children's recreational screen use. METHODS: This study was based on a population-based cross-sectional survey sent between May 2019 and November 2020 to a random sample of 6820 Danish parent-child dyads who answered questions regarding their screen media habits. Children were 6-11 years of age and had to reside with the parent. Multivariable adjusted regression analyses were conducted (in October 2021) separately for screen media use on weekdays and weekend days. RESULTS: The analyses included 5437 parents (41.0 years, 67.6% girls) and 5437 children (8.9 years, 48.2% girls). The adjusted relative odds of excessive amounts of screen use of children (>3 hours/weekday and >4 hours/weekend day) was 5.8 (95% confidence interval (CI) 4.6; 7.3) on weekdays and 7.2 (95% CI 5.9; 8.8) on weekend days comparing the fourth and first quartile of parental screen use. Children of parents in the fourth quartile of parental screen use had 2.1 (95% CI 1.7; 2.5) and 2.5 (95% CI 2.2; 3.0) greater odds of screen use before bedtime on all week and weekend days, respectively. Children of parents who had a positive attitude towards their child's screen use or were at high risk of smartphone addiction had significantly higher screen use and more frequent problematic screen use. CONCLUSIONS: Parent's screen media habits and attitudes were strongly associated with their children's recreational screen use.

VH-Based Mini Q-Body: A Novel Quench-Based Immunosensor.

Quenchbodies (Q-bodies), a type of biosensor, are antibodies labeled with a fluorescent dye near the antigen recognition site. In the absence of an antigen, the dye is quenched by tryptophans in the antibody sequence; however, in its presence, the dye is displaced and therefore de-quenched. Although scFv and Fab are mainly used to create Q-bodies, this is the first report where a single-domain heavy chain VH from a semi-synthetic human antibody library formed the basis. To create a proof of concept "mini Q-body", a human anti-lysozyme single-domain VH antibody C3 was used. Mini Q-bodies were successfully developed using seven dyes. Different responses were observed depending on the dye and linker length; it was concluded that the optimal linker length for the TAMRA dye was C5, and rhodamine 6G was identified as the dye with the largest de-quenching response. Three single-domain antibodies with sequences similar to that of the C3 antibody were chosen, and the results confirmed the applicability of this method in developing mini Q-bodies. In summary, mini Q-bodies are an easy-to-use and time-saving method for detecting proteins.

Glycaemic thresholds for counterregulatory hormone and symptom responses to hypoglycaemia in people with and without type 1 diabetes: a systematic review.

AIM/HYPOTHESIS: The physiological counterregulatory response to hypoglycaemia is reported to be organised hierarchically, with hormone responses usually preceding symptomatic awareness and autonomic responses preceding neuroglycopenic responses. To compare thresholds for activation of these responses more accurately between people with or without type 1 diabetes, we performed a systematic review on stepped hyperinsulinaemic-hypoglycaemic glucose clamps. METHODS: A literature search in PubMed and EMBASE was conducted. We included articles published between 1980 and 2018 involving hyperinsulinaemic stepped hypoglycaemic glucose clamps among people with or without type 1 diabetes. Key exclusion criteria were as follows: data were previously published; other patient population; a clamp not the primary intervention; and an inadequate clamp description. Glycaemic thresholds for counterregulatory hormone and/or symptom responses to hypoglycaemia were estimated and compared using generalised logrank test for interval-censored data, where the intervals were either extracted directly or calculated from the data provided by the study. A glycaemic threshold was defined as the glucose level at which the response exceeded the 95% CI of the mean baseline measurement or euglycaemic control clamp. Because of the use of interval-censored data, we described thresholds using median and IQR. RESULTS: A total of 63 articles were included, whereof 37 papers included participants with type 1 diabetes (n=559; 67.4% male sex, aged 32.7±10.2 years, BMI 23.8±1.4 kg/m2) and 51 papers included participants without diabetes (n=733; 72.4% male sex, aged 31.1±9.2 years, BMI 23.6±1.1 kg/m2). Compared with non-diabetic control individuals, in people with type 1 diabetes, the median (IQR) glycaemic thresholds for adrenaline (3.8 [3.2-4.2] vs 3.4 [2.8-3.9 mmol/l]), noradrenaline (3.2 [3.2-3.7] vs 3.0 [2.8-3.1] mmol/l), cortisol (3.5 [3.2-4.2]) vs 2.8 [2.8-3.4] mmol/l) and growth hormone (3.8 [3.3-3.8] vs. 3.2 [3.0-3.3] mmol/l) all occurred at lower glucose levels in people with diabetes than in those without diabetes (all p≤0.01). Similarly, although both autonomic (median [IQR] 3.4 [3.4-3.4] vs 3.0 [2.8-3.4] mmol/l) and neuroglycopenic (median [IQR] 3.4 [2.8-N/A] vs 3.0 [3.0-3.1] mmol/l) symptom responses were elicited at lower glucose levels in people with type 1 diabetes, the thresholds for autonomic and neuroglycopenic symptoms did not differ for each individual subgroup. CONCLUSIONS/INTERPRETATION: People with type 1 diabetes have glycaemic thresholds for counterregulatory hormone and symptom responses at lower glucose levels than people without diabetes. Autonomic and neuroglycopenic symptoms responses are generated at about similar levels of hypoglycaemia. There was a considerable variation in the methodology of the articles and the high insulin doses in most of the clamps may affect the counterregulatory responses. FUNDING: This article has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement no. 777460. REGISTRATION: This systematic review is registered in PROSPERO (CRD42019120083).

Immobilization-Free Binding and Affinity Characterization of Higher Order Bispecific Antibody Complexes Using Size-Based Microfluidics.

Simultaneous targeting of different antigens by bispecific antibodies (bsAbs) is permitting synergistic binding functionalities with high therapeutic potential, but is also rendering their analysis challenging. We introduce flow-induced dispersion analysis (FIDA) for the in-depth characterization of bsAbs with diverse molecular architectures and valencies under near-native conditions without potentially obstructive surface immobilization. Individual equilibrium dissociation constants are determined in solution, even in higher-order complexes with both antigens involved, hereby allowing the analysis of binding cooperativity and elucidation of a potential interference between the interactions. We further illustrate bispecific binding functionality as incremental increases in complex sizes when the bsAbs are exposed to one or two antigens. The possibility for comprehensive binding analysis with low material consumption and high matrix tolerability irrespective of molecular format and with little optimization renders FIDA a versatile tool for format selection and characterization of complex bi/multispecific protein therapeutics throughout the drug development and biomanufacturing pipeline.

Semi-rational Engineering of a Promiscuous Fatty Acid Hydratase for Alteration of Regioselectivity.

Fatty acid hydratases (FAHs) catalyze regio- and stereo-selective hydration of unsaturated fatty acids to produce hydroxy fatty acids. Fatty acid hydratase-1 (FA-HY1) from Lactobacillus Acidophilus is the most promiscuous and regiodiverse FAH identified so far. Here, we engineered binding site residues of FA-HY1 (S393, S395, S218 and P380) by semi-rational protein engineering to alter regioselectivity. Although it was not possible to obtain a completely new type of regioselectivity with our mutant libraries, a significant shift of regioselectivity was observed towards cis-5, cis-8, cis-11, cis-14, cis-17-eicosapentaenoic acid (EPA). We identified mutants (S393/S395 mutants) with excellent regioselectivity, generating a single hydroxy fatty acid product from EPA (15-OH product), which is advantageous from application perspective. This result is impressive given that wild-type FA-HY1 produces a mixture of 12-OH and 15-OH products at 63 : 37 ratio (12-OH : 15-OH). Moreover, our results indicate that native FA-HY1 is at its limit in terms of promiscuity and regiospecificity, thus it may not be possible to diversify its product portfolio with active site engineering. This behavior of FA-HY1 is unlike its orthologue, fatty acid hydratase-2 (FA-HY2; 58 % sequence identity to FA-HY1), which has been shown earlier to exhibit significant promiscuity and regioselectivity changes by a few active site mutations. Our reverse engineering from FA-HY1 to FA-HY2 further demonstrates this conclusion.

Flexible inclusion of dialogue about psychosocial aspects of life with type 1 diabetes in routine consultations: A study of a questionnaire-based dialogue tool to promote person-centred support.

AIMS: To explore (1) experiences among people with type 1 diabetes and diabetologists of using a questionnaire-based dialogue tool in routine consultations to identify and address psychosocial challenges and (2) experiences of person-centredness in this group compared with a group who did not use the tool. METHODS: In all, 42 people with type 1 diabetes (mean age 54 years, mean diabetes duration 31 years and 60% women) were interviewed and completed an evaluation questionnaire following a routine consultation with the use of a dialogue tool including PAID-5, WHO-5 and open-ended questions. A comparison group of 42 people with type 1 diabetes attending routine consultations without the use of dialogue tools completed evaluation questionnaires. All consultations were audio recorded. Diabetologists were interviewed after completing all test consultations. Interviews were analysed using thematic text condensation. Evaluation questionnaires were analysed using descriptive statistics, chi square tests and Student's two-sided t-tests. RESULTS: Most participants found questions in the dialogue tool relevant to discuss with the diabetologist, and two-thirds were satisfied with the time spent on that. Experiences of people with type 1 diabetes and diabetologists were related to three pathways: (1) the tool supported valuable conversations with the diabetologist, (2) conversations with the diabetologist were unchanged and (3) the tool derailed conversations. All participants reported high levels of person centredness; however, significantly more in the comparison group reported that the diabetologist made them feel at ease (80 vs. 55%) and discussed and planned specific changes with them (93 vs. 67%). CONCLUSION: A questionnaire-based dialogue tool in consultations can support the discussion of psychosocial issues of people with type 1 diabetes. However, flexible and tailored use of the dialogue tool is crucial as consultations may otherwise be derailed.

Recreational screen media use in Danish school-aged children and the role of parental education, family structures, and household screen media rules.

Screen media use is part of most children's everyday lives, but organisations have advised that use should be limited. The aims of this study were to describe 6-11-year-old Danish children's screen device ownership and screen media use (weekdays and weekends), including the role of parental education, family structure and household screen media rules. We conducted a cross-sectional study including 5274 Danish children aged 6-11-years sampled from ten Danish municipalities from May 2019 to November 2020. Characteristics of the sample and source population were obtained from the Danish Health Data Authority. Parent's completed the SCREENS questionnaire, which was developed to assess children's screen media habits. We used inverse probability weighted logistic and linear regression models. Smartphone and laptop ownership was higher with increasing age, and use of screen media varied across day type, age and gender. The proportion of children using screen media more than 4 h/day was 13% (95% CI 12%;14%) for weekdays and 28% (95% CI 27%;29%) for weekend days. Children of parents with medium-length or long educations had statistically significant lower odds of using screen media more than 4 h/day. We found a statistically significant graded relationship between household screen media rules and children's screen media use; the less parents reported presence of rules, the more time their children spent on screen media engagements. Our results suggest that parental educational level and family structure are related to unfavourable screen media habits, and household screen media rules may play an important role for parents to limit children's screen use.

35 Years of health surveys in Denmark: a backbone of public health practice and research.

Denmark has a 35-year history of monitoring health status in the general population through health surveys. In this commentary, we outline the development of health surveys in Denmark from the beginning in 1987 to the present time. We describe how the current systematic framework for the Danish National Health Survey (DNHS) developed. We discuss the methodological basis for the DNHS and describe its application in public health practice and research. Over the years, the DNHS has become an important part of the Danish public health environment. Challenges for the DNHS in the future are to adapt to new trends in public health and at the same time to be able to monitor important changes consistently over time.

The Danish National Health Survey: Study design, response rate and respondent characteristics in 2010, 2013 and 2017.

Aim: This article aims to describe the study design, including descriptive statistics on changes in response rates, characteristics associated with response and response mode distribution, in the Danish National Health Survey (DNHS) in 2010, 2013 and 2017. Methods: Each survey was based on five regional stratified random samples and one national random sample drawn from the Danish Civil Registration System. The subsamples were mutually exclusive. Around 300,000 individuals (aged ⩾16 years) were invited to participate in each survey using a mixed-mode approach (paper/web). A questionnaire with a minimum of 52 questions was used in all subsamples. In 2010 and 2013, invitations were sent via the regular postal service, whereas a secure electronical mail service was used to invite the majority (around 90%) in 2017. Weights accounted for survey design and non-response. Results: Participation decreased from 59.5% in 2010 to 54.0% in 2013 after which it increased to 58.7% in 2017. The proportion answering the web questionnaire increased from 31.0% to 77.4% between 2013 and 2017 and varied from 73.8% to 79.7% between the subsamples in 2017. Overall, the response rate was low among young men and old women and among individuals who were unmarried, had low sociodemographic status, were from ethnic minority backgrounds or were living in the eastern part of Denmark. Conclusions: The survey mode, response mode distribution as well as response rate have changed over time. Weights to handle non-response can be applied to accommodate possible problems in generalising the results. However, efforts should continuously be made to ensure that response is missing at random.

Glycemic variability assessed by continuous glucose monitoring in hospitalized patients with community-acquired pneumonia.

BACKGROUND: Glycemic variability (GV) has only been sparsely studied in patients with community-acquired pneumonia (CAP). This study aimed to quantify in-hospital GV in CAP patients, including determining the impact of type 2 diabetes mellitus (T2DM) and glucocorticoid (GC) treatment on GV. METHODS: This is a prospective cohort study of CAP patients (N = 40) with or without T2DM and treated or not with GCs. The primary endpoint was GV measured as glucose standard deviation (SD), coefficient of variation (CV), and postprandial glucose excursions (PPGE) based on continuous glucose monitoring (CGM). Analysis of glucose data was split into daytime and nighttime when possible. RESULTS: Patients included had a mean age of 74 (range 55 to 91) years. SD (95%CI) increased by a factor of 1.93 (1.40 to 2.66) and 2.29 (1.38 to 3.81) in patients with T2DM and not treated with GCs during the daytime and the nighttime, respectively (both P < 0.01), and by a factor of 1.42 (1.04 to 1.97) in patients treated with GCs but without T2DM during the daytime (P = 0.031) compared to patients without T2DM and not treated with GCs. CV (95%CI) increased by 5.1 (0.0 to 10.1) and 8.1 (1.0 to 15.2) percentage points during the daytime and the nighttime, respectively, in patients with T2DM and not treated with GCs compared to patients without T2DM and not treated with GCs (P = 0.046 and P = 0.026, respectively). PPGE (95% CI) increased during lunch by 2.5 (0.7 to 4.3) mmol/L (45 (13 to 77) mg/dL) in patients with T2DM and treated with GCs compared to patients without T2DM and not treated with GCs (P = 0.018). CONCLUSIONS: CAP patients receiving GCs, especially those with T2DM, are at great risk of developing high GV and therefore require clinical attention to mitigate GV. This applies particularly during the daytime. Results support the 1 to 2-h post-lunch screening procedure for glucocorticoid-induced hyperglycemia in patients without diabetes. SD was positively correlated with hospital length of stay.

Hyperinsulinaemic-hypoglycaemic glucose clamps in human research: a systematic review of the literature.

AIMS/HYPOTHESIS: The hyperinsulinaemic-hypoglycaemic glucose clamp technique has been developed and applied to assess effects of and responses to hypoglycaemia under standardised conditions. However, the degree to which the methodology of clamp studies is standardised is unclear. This systematic review examines how hyperinsulinaemic-hypoglycaemic clamps have been performed and elucidates potential important differences. METHODS: A literature search in PubMed and EMBASE was conducted. Articles in English published between 1980 and 2018, involving adults with or without diabetes, were included. RESULTS: A total of 383 articles were included. There was considerable variation in essential methodology of the hypoglycaemic clamp procedures, including the insulin dose used (49-fold difference between the lowest and the highest rate), the number of hypoglycaemic steps (range 1-6), the hypoglycaemic nadirs (range 2.0-4.3 mmol/l) and the duration (ranging from 5 to 660 min). Twenty-seven per cent of the articles reported whole blood glucose levels, most venous levels. In 70.8% of the studies, a dorsal hand vein was used for blood sampling, with some form of hand warming to arterialise venous blood in 78.8% of these. Key information was missing in 61.9% of the articles. CONCLUSIONS/INTERPRETATION: Although the hyperinsulinaemic-hypoglycaemic clamp procedure is considered the gold standard to study experimental hypoglycaemia, a uniform standard with key elements on how to perform these experiments is lacking. Methodological differences should be considered when comparing results between hypoglycaemic clamp studies. PROSPERO REGISTRATION: This systematic review is registered in PROSPERO (CRD42019120083).

Multiple stressors determine river ecological status at the European scale: Towards an integrated understanding of river status deterioration.

The biota of European rivers are affected by a wide range of stressors impairing water quality and hydro-morphology. Only about 40% of Europe's rivers reach 'good ecological status', a target set by the European Water Framework Directive (WFD) and indicated by the biota. It is yet unknown how the different stressors in concert impact ecological status and how the relationship between stressors and status differs between river types. We linked the intensity of seven stressors to recently measured ecological status data for more than 50,000 sub-catchment units (covering almost 80% of Europe's surface area), which were distributed among 12 broad river types. Stressor data were either derived from remote sensing data (extent of urban and agricultural land use in the riparian zone) or modelled (alteration of mean annual flow and of base flow, total phosphorous load, total nitrogen load and mixture toxic pressure, a composite metric for toxic substances), while data on ecological status were taken from national statutory reporting of the second WFD River Basin Management Plans for the years 2010-2015. We used Boosted Regression Trees to link ecological status to stressor intensities. The stressors explained on average 61% of deviance in ecological status for the 12 individual river types, with all seven stressors contributing considerably to this explanation. On average, 39.4% of the deviance was explained by altered hydro-morphology (morphology: 23.2%; hydrology: 16.2%), 34.4% by nutrient enrichment and 26.2% by toxic substances. More than half of the total deviance was explained by stressor interaction, with nutrient enrichment and toxic substances interacting most frequently and strongly. Our results underline that the biota of all European river types are determined by co-occurring and interacting multiple stressors, lending support to the conclusion that fundamental management strategies at the catchment scale are required to reach the ambitious objective of good ecological status of surface waters.