The prevention of adverse pregnancy outcomes by periodontal treatment during pregnancy (PROBE) intervention study-A controlled intervention study: Protocol paper.

INTRODUCTION: Pregnancy increases the risk of periodontitis due to the increase in progesterone and estrogen. Moreover, periodontitis during pregnancy is associated with development of pregnancy and birth related complications. The aim of this study is to determine, whether periodontal treatment during pregnancy can reduce systemic inflammation and lower the risk of adverse pregnancy and birth related outcomes. METHODS AND ANALYSIS: The PROBE study is a non-randomized controlled intervention study conducted among 600 pregnant women with periodontitis. The women will be recruited among all pregnant women at two Danish hospitals in Region Zealand during their nuchal translucency scan and will subsequently be screened for periodontitis. The intervention group includes 300 pregnant women, who will be offered state-of-the-art periodontal treatment during pregnancy. The control group includes additional 300 pregnant women, who will be offered periodontal treatment after giving birth. Outcome measures include periodontal measures, inflammatory, hormonal and glycaemic markers as well as the prevalence of preterm birth risk, low birth weight and risk markers of gestational diabetes mellitus (GDM) and preeclampsia that will be collected from all screened women and further during pregnancy week 20 and pregnancy week 35 for women enrolled in the intervention. ETHICS AND DISSEMINATION: The study's findings will be published in peer reviewed journals and disseminated at national and international conferences and through social media. The PROBE study is designed to provide important new knowledge as to whether periodontal treatment during pregnancy can reduce the prevalence of complications related to pregnancy and birth. CLINICAL TRIALS REGISTRATION: The study was registered on clinicaltrials.gov (NCT06110143).

Danish Diabetes Birth Registry 2: a study protocol of a national prospective cohort study to monitor outcomes of pregnancies of women with pre-existing diabetes.

INTRODUCTION: Despite technological developments and intensified care, pregnancies in women with pre-existing diabetes are still considered high-risk pregnancies. The rate of adverse outcomes in pregnancies affected by diabetes in Denmark is currently unknown, and there is a limited understanding of mechanisms contributing to this elevated risk. To address these gaps, the Danish Diabetes Birth Registry 2 (DDBR2) was established. The aims of this registry are to evaluate maternal and fetal-neonatal outcomes based on 5 years cohort data, and to identify pathophysiology and risk factors associated with short-term and long-term outcomes of pregnancies in women with pre-existing diabetes. METHODS AND ANALYSIS: The DDBR2 registry is a nationwide 5-year prospective cohort with an inclusion period from February 2023 to February 2028 of pregnancies in women with all types of pre-existing diabetes and includes registry, clinical and questionnaire data and biological samples of mother-partner-child trios. Eligible families (parents age ≥18 years and sufficient proficiency in Danish or English) can participate by either (1) basic level data obtained from medical records (mother and child) and questionnaires (partner) or (2) basic level data and additional data which includes questionnaires (mother and partner) and blood samples (all). The primary maternal outcome is Hemoglobin A1c (HbA1c) levels at the end of pregnancy and the primary offspring endpoint is the birth weight SD score. The DDBR2 registry will be complemented by genetic, epigenetic and metabolomic data as well as a biobank for future research, and the cohort will be followed through data from national databases to illuminate possible mechanisms that link maternal diabetes and other parental factors to a possible increased risk of adverse long-term child outcomes. ETHICS AND DISSEMINATION: Approval from the Ethical Committee is obtained (S-20220039). Findings will be sought published in international scientific journals and shared among the participating hospitals and policymakers. TRIAL REGISTRATION NUMBER: NCT05678543.

Loneliness and the risk of type 2 diabetes.

INTRODUCTION: The incidence of type 2 diabetes is increasing globally. Recent research suggests that loneliness could be a potential risk factor for the development of type 2 diabetes. We aimed to investigate the association between loneliness and type 2 diabetes and the modifying effect of mental disorders. RESEARCH DESIGN AND METHODS: We conducted a prospective study including 465 290 adults (aged ≥16 years) who participated in either the Danish Health and Morbidity Survey or the Danish National Health Survey between 2000 and 2017. Loneliness was based on self-report, while type 2 diabetes was measured using an algorithm combining several health registers including type 2 diabetes patients treated both within the hospital sector and general practice. Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: During a mean follow-up time of 6.3 years, 13 771 individuals (3%) developed type 2 diabetes. Feeling lonely once in a while was associated with a 14% increased risk of type 2 diabetes (95% CI 1.09 to 1.20), while feeling lonely often was associated with a 24% increased risk (95% CI 1.14 to 1.34), independent of sociodemographic factors and body mass index. The association was stronger among individuals without a mental disorder (HR 1.21, 95% CI 1.10 to 1.34 among those feeling lonely often) compared with those with a mental disorder (HR 1.07, 95% CI 0.93 to 1.23). CONCLUSIONS: Loneliness independently increased the risk of type 2 diabetes. The effect was more pronounced in individuals without a mental disorder, as having a mental disorder itself likely increases the risk of type 2 diabetes. These findings emphasize the importance of addressing loneliness as a modifiable risk factor in preventing type 2 diabetes.

Diabetic complications and risk of depression and anxiety among adults with type 2 diabetes.

AIMS: To investigate if diabetic complications increase the risk of depression and/or anxiety among adults with type 2 diabetes. METHODS: This register-based, prospective study included 265,799 adult individuals diagnosed with type 2 diabetes between 1997 and 2017 without a recent history of depression or anxiety. Diabetic complications included cardiovascular disease, amputation of lower extremities, neuropathy, nephropathy and retinopathy. Both diabetic complications and depression and anxiety were defined by hospital contacts and prescription-based medication. All individuals were followed from the date of type 2 diabetes diagnosis until the date of incident depression or anxiety, emigration, death or 31 December 2018, whichever occurred first. RESULTS: The total risk time was 1,915,390 person-years. The incidence rate of depression and/or anxiety was 3368 per 100,000 person-years among individuals with diabetic complications and 1929 per 100,000 person-years among those without. Having or developing any diabetic complication was associated with an increased risk of depression and/or anxiety (HR 1.77, 95% CI 1.73-1.80). The risk for depression and/or anxiety was increased for all types of diabetic complications. The strongest association was found for amputation of lower extremities (HR 2.16, 95% CI 2.01-2.31) and the weakest for retinopathy (HR 1.13, 95% CI 1.09-1.17). CONCLUSION: Individuals with type 2 diabetes and diabetic complications are at increased risk of depression and anxiety. This points towards the importance of an increased clinical focus on mental well-being among individuals with type 2 diabetes and complications.

Predicting diabetes-related conditions in need of intervention: Lolland-Falster Health Study, Denmark.

In the Danish population, about one-in-ten adults have prediabetes, undiagnosed, poorly or potentially sub-regulated diabetes, for short DMRC. It is important to offer these citizens relevant healthcare intervention. We therefore built a model for prediction of prevalent DMRC. Data were derived from the Lolland-Falster Health Study undertaken in a rural-provincial area of Denmark with disadvantaged health. We included variables from public registers (age, sex, age, citizenship, marital status, socioeconomic status, residency status); from self-administered questionnaires (smoking status, alcohol use, education, self-rated health, dietary habits, physical activity); and from clinical examinations (body mass index (BMI), pulse rate, blood pressure, waist-to-hip ratio). Data were divided into training/testing datasets for development and testing of the prediction model. The study included 15,801 adults; of whom 1,575 with DMRC. Statistically significant variables in the final model included age, self-rated health, smoking status, BMI, waist-to-hip ratio, and pulse rate. In the testing dataset this model had an area under the curve (AUC) = 0.77 and a sensitivity of 50% corresponding to a specificity of 84%. In a health disadvantaged Danish population, presence of prediabetes, undiagnosed, or poorly or potentially sub-regulated diabetes could be predicted from age, self-rated health, smoking status, BMI, waist-to-hip ratio, and pulse rate. Age is known from the Danish personal identification number, self-rated health and smoking status can be obtained from simple questions, and BMI, waist-to-hip ratio, and pulse rate can be measured by any person in health care and potentially by the person him/her-self. Our model might therefore be useful as a screening tool.

Effects of DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors and sulphonylureas on mortality, cardiovascular and renal outcomes in type 2 diabetes: A network meta-analyses-driven approach.

AIMS: The aim of our meta-analyses was to compare the effects of glucose-lowering drugs on mortality, cardiovascular and renal endpoints for a range of type 2 diabetes (T2D) subgroups defined by their specific cardiovascular risk profile. METHODS: Meta-analyses comparing drugs within the classes of GLP-1RAs and SGLT-2 inhibitors were performed and compared to sulphonylureas and DPP-4 inhibitors with available cardiovascular outcome trials. The comparison between the different classes of glucose-lowering drugs included analyses of T2D populations with low risk and high risk for cardiovascular disease including populations with established cardiovascular disease and/or kidney disease. Outcomes included mortality, major cardiovascular adverse events (MACE), hospitalisation for heart failure (HHF) and a composite renal endpoint as applied in the underlying clinical trials. RESULTS: SGLT-2 inhibitors and GLP-1RAs showed beneficial effects on mortality and MACE compared to the classes of DPP-4 inhibitors and sulphonylureas. SGLT-2 inhibitors were shown to be the most effective treatment in terms of HHF and kidney disease. Metformin was used as background therapy for the vast majority of participants in all included studies. Overall, the absolute effects of SGLT-2 inhibitors and GLP-1RAs on these important outcomes were evident for patients with established or at high risk for cardiovascular disease but limited for the low-risk subgroup. CONCLUSIONS: The findings from our analyses substantiate the relevance of treatment with SGLT-2 inhibitors or GLP-1RAs as an add-on to metformin in patients with T2D and a high risk for cardiovascular disease, and furthermore, support the recommendation for SGLT-2 inhibitor treatment in patients with T2D and heart failure or established kidney disease.

Validity of Danish public criteria for providing flash glucose monitoring to participants with type 1 diabetes-An explorative cohort study.

INTRODUCTION: Flash glucose monitor (FGM) use is increasing. A set of Danish criteria for regulating the use has been released. We assessed their validity. METHODS: Patients with type 1 diabetes attending our clinic were offered Freestyle Libre Sensor for 12 months and stratified into fulfilling the Danish regional criteria (RC+) or not (RC-). Primary endpoint was achieving individualized target HbA1c. Secondary endpoints were HbA1c reduction ≥5%, time in range (TIR), time below range (TBR), daily scans, change in median HbA1c, and noted experiences. RESULTS: Two hundred seventy-eight participants were included. Forty-four participants met target HbA1c after 1 year. No difference between RC+ and RC- was observed (p = .136). Higher age was associated with probability to meet target HbA1c (RR = 3.15, [95% CI: 1.15, 8.62]) as was frequent scans (RR = 1.88, [95% CI: 0.99, 3.57]). One hundred twenty-three participants met an HbA1c reduction ≥5%, the majority represented in RC+ (p = .023). Higher baseline HbA1c was associated with a reduction of HbA1c ≥5% after 1 year (RR = 1.97, [95% CI: 1.40, 2.78]). There was no difference between RC+ and RC- in TIR, TBR, and daily scans. Positive experiences dominated from both participants and healthcare professionals. More positive experiences were noted from healthcare professionals in RC- (p = .003) but no difference in reported experiences among participants in RC+ and RC- (p = .880). CONCLUSION: The Danish Regional Criteria seems not a valid tool for regulation of FGM. Participants of older age and participants with more frequent daily scans might benefit more from FGM.

Burden of prediabetes, undiagnosed, and poorly or potentially sub-controlled diabetes: Lolland-Falster health study.

BACKGROUND: This study aimed to investigate prevalence and risk factors for prediabetes, undiagnosed diabetes mellitus, poorly and potentially sub-controlled diabetes in a rural-provincial general adult population in Denmark. METHODS: Using cross-sectional data from the Lolland-Falster Health Study, we examined a total of 10,895 individuals aged 20 years and above. RESULTS: Prevalence of prediabetes was 5.8% (men: 6.1%; women: 5.5%); of undiagnosed diabetes 0.8% (men: 1.0%; women: 0.5%); of poorly controlled diabetes 1.2% (men: 1.5%; women: 0.8%); and of potentially sub-controlled diabetes 2% (men: 3.0%; women: 1.3%). In total, 9.8% of all participants had a diabetes-related condition in need of intervention; men at a higher risk than women; RR 1.41 (95% CI 1.26-1.58); person aged + 60 years more than younger; RR 2.66 (95% CI 2.34-3.01); obese more than normal weight person, RR 4.51 (95% CI 3.79-5.38); smokers more than non-smokers, RR 1.38 (95% CI 1.19-1.62); persons with self-reported poor health perception more than those with good, RR 2.59 (95% CI 2.13-3.15); low leisure time physical activity more than those with high, RR 2.64 (95% CI 2.17-3.22); and persons with self-reported hypertension more than those without, RR 3.28 (95% CI 2.93-3.68). CONCLUSIONS: In the Lolland-Falster Health Study, nearly 10% of participants had prediabetes, undiagnosed diabetes, poorly controlled, or potentially sub-controlled diabetes. The risk of these conditions was more than doubled in persons with self-reported poor health perception, self-reported hypertension, low leisure time physical activity, or measured obesity, and a large proportion of people with diabetes-related conditions in need of intervention can therefore be identified relatively easily.

suPAR as a biomarker for risk of readmission and mortality in the acute medical setting.

INTRODUCTION: The urokinase-type plasminogen activator receptor (uPAR) and its ligand (suPAR) are involved in numerous physiological and pathological pathways. Previous studies have shown that an elevated plasma suPAR level is associated with disease severity and mortality. The aim of this prospective observational study was to determine if the suPAR level was associated with readmission and mortality in the acute medical setting. METHODS: Plasma suPAR levels were measured in 1,036 patients at admission. Follow-up ranged 3-10 months. Cox proportional hazards model was used to assess the relative contribution of different risk factors to mortality and readmission. The ANOVA test and Pearson's chi-squared test were used to compare suPAR tertile level with various variables. RESULTS: The highest suPAR tertile level was significantly associated with mortality within 30 days after discharge, with a 6.66 hazard ratio (HR). Similar associations were found with readmission within the maximum observation period (HR = 2.26) and within 30 days (HR = 2.08), although the latter became insignificant when covariates were included. CONCLUSIONS: This study confirms previous findings of increased mortality and adds the finding that increased long-term readmission rates are associated with elevated suPAR levels. The present data do, however, not indicate that suPAR may serve as an independent biomarker for increased risk of short-term readmission in the acute medical setting. FUNDING: This study was funded by a grant from ViroGates A/S, the company that produces the suPARnostic assay. TRIAL REGISTRATION: No: H-B-2009-075.

[High hospital standardized mortality ratio does not always indicate low quality].

Hospital standardized mortality ratio (HSMR) is increasingly used to assess quality of care. At Frederiksberg Hospital HSMR increased significantly during the first and second quarter in 2012. We therefore reviewed records of all deceased, including patients deceased during the comparative period in 2011 (n = 413). Information about cancer and infection with Clostridium difficile was specifically noted. We found that the increasing HSMR reflected an increase in the number of terminal cancer patients. Thus, insufficient adjustment for a change in case-mix explained the higher HSMR.

Five easy equations for patient flow through an emergency department.

INTRODUCTION: Queue models are effective tools for framing management decisions and Danish hospitals could benefit from awareness of such models. Currently, as emergency departments (ED) are under reorganization, we deem it timely to empirically investigate the applicability of the standard "M/M/1" queue model in order to document its relevance. MATERIAL AND METHODS: We compared actual versus theoretical distributions of hourly patient flow from 27,000 patient cases seen at Frederiksberg Hospital's ED. Formulating equations for arrivals and capacity, we wrote and tested a five equation simulation model. RESULTS: The Poisson distribution fitted arrivals with an hour-of-the-day specific parameter. Treatment times exceeding 15 minutes were well-described by an exponential distribution. The ED can be modelled as a black box with an hourly capacity that can be estimated either as admissions per hour when the ED operates full hilt Poisson distribution or from the linear dependency of waiting times on queue number. The results show that our ED capacity is surprisingly constant despite variations in staffing. These findings led to the formulation of a model giving a compact framework for assessing the behaviour of the ED under different assumptions about opening hours, capacity and workload. CONCLUSION: The M/M/1 almost perfectly fits our. Thus modeling and simulations have contributed to the management process. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

[The treatment of post stroke-depression and emotionalism in clinical practice]. / Antidepressionsbehandling i klinisk praksis på apopleksiafsnit.

INTRODUCTION: Depression and emotionalism are major consequences of stroke. The aim of this study was to assess the treatment of post stroke depression and emotionalism in clinical practice. MATERIALS AND METHODS: Retrospective cohort study based on consecutive series of patients with acute stroke admitted to a specialized stroke unit. RESULTS: 180 patients were identified (f/m: 92/88; age: 73 +/- 20 years, median length of stay; 18 days). At admission 29 patients (16%) were already receiving medical treatment for depression. During hospitalization a further 24 (16%; CI 10-22%) initially untreated patients started treatment. The indication to treat was referred to in 19 cases (13: depression, 6: emotionalism). Formal psychiatric examination or rating was not applied. In one case the treatment was stopped because of side effects. The dose of medicine was adjusted in one case due to insufficient effect of treatment. None of the discharge summaries indicated the expected duration of treatment. CONCLUSIONS: The number of patients being treated during hospitalization was less than expected compared to the expected incidence of post stroke depression and emotionalism. The indication to treat, the duration of treatment and the incidence of side effects was not sufficiently documented. Prescription practice and evaluation of treatment effect may therefore be far from optimal.

Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial.

OBJECTIVES: To evaluate the long term effects of perioperative beta blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery. DESIGN: Randomised placebo controlled and blinded multicentre trial. Analyses were by intention to treat. SETTING: University anaesthesia and surgical centres and one coordinating centre. PARTICIPANTS: 921 patients aged > 39 scheduled for major non-cardiac surgery. INTERVENTIONS: 100 mg metoprolol controlled and extended release or placebo administered from the day before surgery to a maximum of eight perioperative days. MAIN OUTCOME MEASURES: The composite primary outcome measure was time to all cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure. Secondary outcome measures were time to all cause mortality, cardiac mortality, and non-fatal cardiac morbidity. RESULTS: Mean duration of intervention was 4.6 days in the metoprolol group and 4.9 days in the placebo group. Metoprolol significantly reduced the mean heart rate by 11% (95% confidence interval 9% to 13%) and mean blood pressure by 3% (1% to 5%). The primary outcome occurred in 99 of 462 patients in the metoprolol group (21%) and 93 of 459 patients in the placebo group (20%) (hazard ratio 1.06, 0.80 to 1.41) during a median follow-up of 18 months (range 6-30). All cause mortality was 16% (74/462) in the metoprolol group and 16% (72/459) in the placebo group (1.03, 0.74 to 1.42). The difference in risk for the proportion of patients with serious adverse events was 2.4% (- 0.8% to 5.6%). CONCLUSIONS: Perioperative metoprolol did not significantly affect mortality and cardiac morbidity in these patients with diabetes. Confidence intervals, however, were wide, and the issue needs reassessment. TRIAL REGISTRATION: Current Controlled Trials ISRCTN58485613.

The effects of a randomised multi-centre trial and international accreditation on availability and quality of clinical guidelines.

PURPOSE: To examine the availability and quality of clinical guidelines on perioperative diabetes care in hospital units before and after a randomised clinical trial (RCT) and international accreditation. DESIGN/METHODOLOGY/APPROACH: Interventional "before-after" study in 51 units (38 surgical and 13 anaesthetic) in nine hospitals participating in a RCT in the greater Copenhagen area; 27 of the units also underwent international accreditation. FINDINGS: The proportion of units with guidelines increased from 24/51 (47 percent) units before to 38/51 (75 percent) units after the trial. Among the 27 units without guidelines before the trial, significantly more accredited units compared to non-accredited units had a guideline after the trial (9/10 (90 percent) compared to 5/17 (29 percent). The quality of the systematic development scale and the clinical scales improved significantly after the trial in both accredited units (both p < 0.001) and in non-accredited units (both p < 0.02). The improvement of the systematic development scale was significantly higher in accredited than in non-accredited units (p < 0.01). ORIGINALITY/VALUE: The combination of conducting both the DIPOM Trial and international accreditation led to a significant improvement of both dissemination and quality of guidelines on perioperative diabetic care.

The Diabetic Postoperative Mortality and Morbidity (DIPOM) trial: rationale and design of a multicenter, randomized, placebo-controlled, clinical trial of metoprolol for patients with diabetes mellitus who are undergoing major noncardiac surgery.

BACKGROUND: Recent trials suggest that perioperative beta-blockade reduces the risk of cardiac events in patients with a risk of myocardial ischemia who are undergoing noncardiac surgery. Patients with diabetes mellitus are at a high-risk for postoperative cardiac morbidity and mortality. They may, therefore, benefit from perioperative beta-blockade. METHODS: The Diabetic Postoperative Mortality and Morbidity (DIPOM) trial is an investigator-initiated and -controlled, centrally randomized, double-blind, placebo-controlled, multicenter trial. We compared the effect of metoprolol with placebo on mortality and cardiovascular morbidity rates in patients with diabetes mellitus who were beta-blocker naive, >or=40 years old, and undergoing noncardiac surgery. The study drug was given during hospitalization for a maximum of 7 days beginning the evening before surgery. The primary outcome measure is the composite of all-cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure leading to hospitalization or discovered or aggravated during hospitalization. Follow-up involves re-examination of patients at 6 months and collection of mortality and morbidity data via linkage to public databases. The study was powered on the basis of an estimated 30% 1-year event rate in the placebo arm and a 33% relative risk reduction in the metoprolol arm. The median follow-up period was 18 months. RESULTS: Enrollment started in July 2000 and ended in June 2002. A total of 921 patients were randomized, and 54% of these patients had known cardiac disease, hypertension, or both. CONCLUSION: The results of this study may have implications for reduction of perioperative and postoperative risk in patients with diabetes mellitus who are undergoing major noncardiac surgery.

Hyperparathyroidism and subsequent cancer risk in Denmark.

BACKGROUND: There is increasing evidence that hyperparathyroidism (HPT), a condition that leads to elevated serum calcium levels, is associated with endocrine and other malignancies, suggesting a possible causal link between HPT and carcinoma. METHODS: To investigate the relation of HPT to subsequent cancer risk, the authors conducted a record-linkage study among 2425 patients who were diagnosed with HPT in Danish hospitals. Patients were identified in hospital discharge records, and records were then linked with the Danish National Cancer Registry for the years 1977-1993 to identify cancer incidence. To estimate cancer risk, standardized incidence ratios (SIRs) were computed. RESULTS: After excluding patients who were diagnosed in the first year of follow-up, a total of 219 malignancies were observed, resulting in an SIR of 1.25 (95% confidence interval [95%CI], 1.1-1.4). Cancer risk among women was higher than among men. Among those with primary (idiopathic) HPT, hematopoetic malignancies were elevated significantly (SIR, 1.88; 95%CI, 1.0-3.2; based on 13 patients), with the excess derived primarily from 4 observed patients with multiple myeloma. Patients with secondary HPT had an insignificantly increased risk of overall cancers. Patients who were diagnosed with other or unspecified types of HPT had significant increases in carcinoma of the urinary tract (SIR, 2.71; 95%CI, 1.2-5.3; based on 8 patients) and carcinoma of the thyroid gland (SIR, 21.19; 95%CI, 4.3-61.9; based on 3 patients). CONCLUSIONS: Future studies should monitor whether specific endocrine alterations associated with HPT may affect the long-term risk of hematopoetic, thyroid, and urinary tract carcinomas.