The COVIDPregDK Study: A national survey on pregnancy during the early COVID-19 pandemic in Denmark.

AIM: We aimed to describe the aim, data collection and content from a survey completed among pregnant women during the first peak of the COVID-19 pandemic in Denmark. METHODS: The declaration of the COVID-19 pandemic in early 2020 challenged pregnant women's mental well-being due to a concern for their unborn child and their need for healthcare services through pregnancy and birth. To explore how the COVID-19 pandemic and the intensified measures such as the lockdown of Denmark impacted pregnant women's well-being and mental health, we conducted a questionnaire survey in the spring of 2020 when the COVID-19 pandemic was at its first peak, and the consequences for pregnant women and the unborn child were very uncertain. All women residing in Denmark and registered with an ongoing pregnancy on 24 April 2020 were invited to participate. The questionnaire included background information, variables on COVID-19 symptoms and validated batteries of questions on loneliness, anxiety, stress, quality of life, meditation and prayers. Additional questions were included to examine concerns related to pregnancy and childbirth during the pandemic. COHORT CHARACTERISTICS: Almost 18,000 women answered the questionnaire, which represents 60% of all invited women who experienced a national lockdown for the first time. Their median age was 30 years, and they were more likely to be multiparous. CONCLUSIONS: Data from the COVIDPregDK Study will enable us to gain valuable knowledge on how the pandemic, the intensified measures from the health authorities and the national lockdown affected pregnant women's mental health and their concerns during the COVID-19 pandemic.

Concerns about transmission, changed services and place of birth in the early COVID-19 pandemic: a national survey among Danish pregnant women. The COVIDPregDK study.

BACKGROUND: The outbreak of the COVID-19 pandemic caused great uncertainty about causes, treatment and mortality of the new virus. Constant updates of recommendations and restrictions from national authorities may have caused great concern for pregnant women. Reports suggested an increased number of pregnant women choosing to give birth at home, some even unassisted ('freebirth') due to concerns of transmission in hospital or reduction in birthplace options. During April and May 2020, we aimed to investigate i) the level of concern about coronavirus transmission in Danish pregnant women, ii) the level of concern related to changes in maternity services due to the pandemic, and iii) implications for choice of place of birth. METHODS: We conducted a nationwide cross-sectional online survey study, inviting all registered pregnant women in Denmark (n = 30,009) in April and May 2020. RESULTS: The response rate was 60% (n = 17,995). Concerns of transmission during pregnancy and birth were considerable; 63% worried about getting severely ill whilst pregnant, and 55% worried that virus would be transmitted to their child. Thirtyeight percent worried about contracting the virus at the hospital. The most predominant concern related to changes in maternity services during the pandemic was restrictions on partners' attendance at birth (81%). Especially nulliparous women were concerned about whether cancelled antenatal classes or fewer physical midwifery consultations would affect their ability to give birth or care for their child postpartum.. The proportion of women who considered a home birth was equivalent to pre-pandemic home birth rates in Denmark (3%). During the temporary discontinue of public home birth services, 18% of this group considered a home birth assisted by a private midwife (n = 125), and 6% considered a home birth with no midwifery assistance at all (n = 41). CONCLUSION: Danish pregnant womens' concerns about virus transmission to the unborn child and worries about contracting the virus during hospital appointments were considerable during the early pandemic. Home birth rates may not be affected by the pandemic, but restrictions in home birth services may impose decisions to freebirth for a small proportion of the population.

SARS-CoV-2 infection in pregnancy in Denmark-characteristics and outcomes after confirmed infection in pregnancy: A nationwide, prospective, population-based cohort study.

INTRODUCTION: Assessing the risk factors for and consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy is essential to guide clinical care. Previous studies on SARS-CoV-2 infection in pregnancy have been among hospitalized patients, which may have exaggerated risk estimates of severe outcomes because all cases of SARS-CoV-2 infection in the pregnant population were not included. The objectives of this study were to identify risk factors for and outcomes after SARS-CoV-2 infection in pregnancy independent of severity of infection in a universally tested population, and to identify risk factors for and outcomes after severe infection requiring hospital admission. MATERIAL AND METHODS: This was a prospective population-based cohort study in Denmark using data from the Danish National Patient Register and Danish Microbiology Database and prospectively registered data from medical records. We included all pregnancies between March 1 and October 31, 2020 and compared women with a positive SARS-CoV-2 test during pregnancy to non-infected pregnant women. Cases of SARS-CoV-2 infection in pregnancy were both identified prospectively and through register linkage to ensure that all cases were identified and that cases were pregnant during infection. Main outcome measures were pregnancy, delivery, maternal, and neonatal outcomes. Severe infection was defined as hospital admission due to coronavirus disease 2019 (COVID-19) symptoms. RESULTS: Among 82 682 pregnancies, 418 women had SARS-CoV-2 infection during pregnancy, corresponding to an incidence of 5.1 per 1000 pregnancies, 23 (5.5%) of which required hospital admission due to COVID-19. Risk factors for infection were asthma (odds ratio [OR] 2.19, 95% CI 1.41-3.41) and being foreign born (OR 2.12, 95% CI 1.70-2.64). Risk factors for hospital admission due to COVID-19 included obesity (OR 2.74, 95% CI 1.00-7.51), smoking (OR 4.69, 95% CI 1.58-13.90), infection after gestational age (GA) 22 weeks (GA 22-27 weeks: OR 3.77, 95% CI 1.16-12.29; GA 28-36 weeks: OR 4.76, 95% CI 1.60-14.12), and having asthma (OR 4.53, 95% CI 1.39-14.79). We found no difference in any obstetrical or neonatal outcomes. CONCLUSIONS: Only 1 in 20 women with SARS-CoV-2 infection during pregnancy required admission to hospital due to COVID-19. Risk factors for admission comprised obesity, smoking, asthma, and infection after GA 22 weeks. Severe adverse outcomes of SARS-CoV-2 infection in pregnancy were rare.

Prevalence of long-term opioid therapy in spine center outpatients the spinal pain opioid cohort (SPOC).

PURPOSE: No reference material exists on the scope of long-term problems in novel spinal pain opioid users. In this study, we evaluate the prevalence and long-term use of prescribed opioids in patients of the Spinal Pain Opioid Cohort. METHODS: The setting was an outpatient healthcare entity (Spine Center). Prospective variables include demographics, clinical data collected in SpineData, and The Danish National Prescription Registry. Patients with a new spinal pain episode lasting for more than two months, aged between 18 and 65 years, who had their first outpatient visit. Based on the prescription of opioids from 4 years before the first spine center visit to 5 years after, six or more opioid prescriptions in a single 1-year interval fulfilled the main outcome criteria Long-Term Opioid Therapy (LTOT). RESULTS: Overall, of 8356 patients included in the cohort, 4409 (53%) had one or more opioid prescriptions in the registered nine years period. Of opioid users, 2261 (27%) were NaiveStarters receiving their first opioid prescription after a new acute pain episode; 2148(26%) PreStarters had previously received opioids. The prevalence of LTOT in PreStarters/NaiveStarters was 17.2%/11.2% in their first outpatient year. Similar differences between groups were seen in all follow-up intervals. In the last follow-up year, LTOT prevalence in Prestarters/NaiveStarters was 12.5%/7.0%. CONCLUSIONS: Previous opioid treatment-i.e., before a new acute spinal pain episode and referral to a Spine Center-doubled the risk of LTOT 5 years later. The results underscore clinicians' obligation to carefully and individually weigh the benefits against the risks of prescribing opioid therapy. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Obstetric synthetic oxytocin use and subsequent hyperactivity/inattention problems in Danish children.

INTRODUCTION: The objective was to examine the association between obstetric synthetic oxytocin use and hyperactivity/inattention problems in offspring. MATERIAL AND METHODS: We identified children born in 2000-2003, enrolled in the Danish National Birth Cohort, with data on the Strengths and Difficulties Questionnaire (SDQ) reported by parents at age seven (n = 33 896) and age 11 (n = 27 561) and the children themselves around age 11 (n = 27 251). Information on oxytocin administration was provided in the Medical Birth Register. We estimated mean differences and odds ratios for childhood hyperactivity/inattention problems according to oxytocin exposure. RESULTS: Synthetic oxytocin was administered in 26% of the deliveries. We did not find the use of synthetic oxytocin during birth to be associated with childhood hyperactivity/inattention problems, whether analyzed in linear or logistic regression models. CONCLUSIONS: Our findings do not support any effects of obstetric use of synthetic oxytocin on hyperactivity/inattention problems in children when measured with the SDQ subscale at 7 or 11 years of age.

Risk of post-injection endophthalmitis peaks within the first three injections of anti-vascular endothelial growth factor therapy: A nationwide registry-based study.

PURPOSE: To report the incidence of post-injection endophthalmitis (PIE) and the cumulative risk associated with repeated injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF). METHODS: We employed nationwide registries in Denmark to include all individuals aged ≥40 years who received at least one intravitreal anti-VEGF injection in 2007-2022. Our primary endpoint PIE was identified using specific diagnostic codes for endophthalmitis and procedure codes for vitreous biopsy within 10 days prior to and 120 days post-injection. Patients were stratified according to the underlying diagnoses for which they received the treatment. The relative risk (RR) for PIE was calculated between groups based on the number of injections received by the patients. RESULTS: We identified 60 825 patients who received intravitreal anti-VEGF treatment during study time, with a median age of 77.2 years and females constituting 58.1%. We identified 232 cases of PIE after 1 051 549 injections during follow-up, resulting in an incidence of 0.022% [95% CI 0.019%-0.025%]. Despite a linear growth in annual anti-VEGF use, the incidence remained stable at 0.020% [95% CI 0.017%-0.023%] from 2013 to 2022. Compared to patients receiving 1-3 injections, RR for patients receiving 4-20, 21-40, and >40 injections were 0.46 [95% CI 0.34-0.63], 0.32 [95% CI 0.21-0.50], and 0.54 [95% CI 0.36-0.81], respectively. Findings were similar across the different diagnoses. CONCLUSIONS: Based on 16 years of nationwide registry data, this study identified a low and stable incidence of PIE. Notably, the highest risk of endophthalmitis was within the first three anti-VEGF injections.

VEGF Inhibition Associates With Decreased Risk of Mortality in Patients With Neovascular Age-related Macular Degeneration.

Purpose: Controversy exists regarding the systemic safety of intravitreal VEGF inhibitors in the treatment of neovascular age-related macular degeneration (nAMD). We aimed to investigate the potential impact of VEGF inhibitor treatment on the risk of all-cause mortality and cardiovascular disease (CVD) among patients with nAMD. Design: A nationwide register-based cohort study with 16 years follow-up. Participants: Patients with nAMD exposed with VEGF inhibitors (n = 37 733) and unexposed individuals without nAMD (n = 1 897 073) aged ≥ 65 years residing in Denmark between January 1, 2007, and December 31, 2022. Methods: Cox proportional hazards analysis was conducted to assess the effect of intravitreal VEGF inhibitor treatment on all-cause mortality and incident CVD. Main Outcome Measures: In a predefined analysis plan we defined primary outcomes as hazard ratios (HRs) of all-cause mortality and a composite CVD endpoint in patients with nAMD treated with VEGF inhibitors compared with individuals without nAMD. The secondary outcomes encompassed analyses that explored the impact of the number of doses and the association between exposure and outcome over a specific time period. Results: Overall, 63.7% of patients with nAMD were women with an average age of 69.9 years (interquartile range 65.0-76.0 years). Patients exposed to VEGF inhibitors demonstrated a reduced risk of all-cause mortality compared with individuals without nAMD (HR, 0.79; 95% confidence interval [CI], 0.78-0.81), and an increased risk of composite CVD (HR, 1.04; 95% CI, 1.01-1.07). The decreased risk of all-cause mortality persisted, but there was no significant association between VEGF inhibitor treatment and CVD when patients with nAMD were grouped by the number of doses or considered exposed within 60 days postinjection. Conclusions: Our study revealed a decreased risk of all-cause mortality and a 4% increased risk of CVD among patients with nAMD exposed with VEGF inhibitors. The decreased risk of mortality is unlikely to be directly pathophysiologically related to VEGF inhibitor treatment. Instead, we speculate that patients undergoing VEGF inhibitor treatment are, on average, individuals in good health with adequate personal resources. Therefore, they also have a higher likelihood of overall survival. These findings strongly support the safety of VEGF inhibitor treatment in terms of all-cause mortality and CVD among patients with nAMD. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Risk of Diabetic Retinopathy According to Subtype of Type 2 Diabetes.

Type 2 diabetes is a heterogeneous disease that can be subdivided on the basis of ß-cell function and insulin sensitivity. We investigated the presence, incidence, and progression of diabetic retinopathy (DR) according to subtypes of type 2 diabetes. In a national cohort, we identified three subtypes of type 2 diabetes: classical, hyperinsulinemic, and insulinopenic type 2 diabetes, based on HOMA2 measurements. From the Danish Registry of Diabetic Retinopathy we extracted information on level of DR. We used several national health registries to link information on comorbidity, medications, and laboratory tests. We found individuals with hyperinsulinemic type 2 diabetes were less likely to have DR at entry date compared with those with classical type 2 diabetes, whereas individuals with insulinopenic type 2 diabetes were more likely to have DR. In multivariable Cox regression analysis, individuals with hyperinsulinemic type 2 diabetes had a decreased risk of both incidence and progression of DR compared to those with classical type 2 diabetes. We did not find any clear difference in risk of incident or progression of DR in individuals with insulinopenic compared to classical type 2 diabetes. These findings indicate that subcategorization of type 2 diabetes is important in evaluating the risk of DR.

Diabetic retinopathy as an independent marker of cardiovascular disease in type 1 diabetes: Results from a nationwide longitudinal matched case-cohort study.

PURPOSE: To investigate diabetic retinopathy (DR) as a potential marker of cardiovascular disease (CVD) in adults with type 1 diabetes attending the Danish DR-screening programme and non-diabetes adults. METHODS: In this registry-based matched case-cohort study, we identified 16 547 adults with type 1 diabetes, who were registered in the Danish Registry of Diabetic Retinopathy (DiaBase). Each case was age- and sex-matched by five non-diabetes individuals (n = 82 399), and odds ratios (ORs) and hazard ratios (HRs) were estimated for incident and upcoming CVD in multivariable models. RESULTS: Adults with type 1 diabetes (median age 44.5 years, 57.6% male) were more likely to have prevalent CVD (OR 1.29; 95% CI, 1.20-1.38) and to develop CVD within 5 years (HR 1.19; 95% CI, 1.08-1.30) as compared to non-diabetes control. However, adults without DR were less likely to develop CVD (HR 0.84; 95% CI, 0.72-0.97) compared to the reference population. For adults with type 1 diabetes, there was an increasing risk for incident CVD for increasing levels of DR (HR 1.33, 1.95, 1.71 and 2.39 for DR-levels 1-4, respectively). Patients with CVD at the time of the first screening had a higher risk to develop DR during follow-up (HR 1.23; 95% CI, 1.02-1.49). CONCLUSION: In a nationwide matched case-cohort study adjusted for potential confounders, DR was identified as an independent marker of prevalent and incident CVD in type 1 diabetes with increasing risk demonstrated for higher levels of DR. Likewise, CVD also independently predicted the risk of incident DR.

Presence and development of diabetic retinopathy in 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy.

PURPOSE: To evaluate the five-year incidence of diabetic retinopathy (DR) and associated risk markers in patients with type 1 diabetes in the national Danish DR-screening programme. METHODS: Based on national data, we included all 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy, who attended the national screening programme in the period 2013-2018. According to the worse eye at first screening, DR was classified (levels 0-4) and linked with various national health registries to retrieve information on diabetes duration, systemic comorbidity, and medication. RESULTS: At first screening, median age and duration of diabetes were 45.0 and 16.7 years, and 57.5% were males. The prevalence and five-year incidences for DR and progression to proliferative DR (PDR) were 44.2%, 8.9% and 2.0%, respectively. In multivariable Cox models, the incidence endpoints were associated with duration of diabetes (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.63-1.89, and HR 2.04, 95% CI 1.73-2.40 per 10 years), moderately low Charlson Comorbidity Index score (HR 1.27, 95% CI 1.10-1.47, and HR 2.80, 95% CI 2.23-3.51), and use of blood pressure lowering medication (HR 1.20, 95% CI 1.05-1.36, and HR 1.98, 95% CI 1.53-2.57). CONCLUSION: In a study of all patients with type 1 diabetes from the Danish DR-screening programme, we identified duration of diabetes, systemic disease and use of anti-hypertensive treatment as consistent risk markers for incident and progressive DR.

Patient perspectives and barriers in the treatment of neovascular age-related macular degeneration in Denmark: a qualitative study.

OBJECTIVES: This qualitative study aims to identify patient-reported barriers to treatment for neovascular age-related macular degeneration (nAMD) and investigate their impact on quality of life. DESIGN: Using a qualitative explorative design. SETTING: Semi-structured individual or dyadic interviews were conducted with patients and their relatives. PARTICIPANTS: Twenty-one patients completed the interview, with four of them having a relative present. INTERVENTIONS: Gadamer's hermeneutics guided the epistemological approach, and maximum variation sampling was employed to capture diverse patient experiences. An advisory board consisting of patients, relatives and ophthalmologists ensured the relevance of the study. Thematic analysis was conducted using NVivo software. PRIMARY AND SECONDARY OUTCOME MEASURES: To investigate patient-reported barriers to the recommended treatment for nAMD and impact on quality of life. RESULTS: The study included 21 patients with nAMD, with a median age of 79 years. Five themes emerged: (1) good compliance with intravitreal treatment, (2) the dual role of relatives, (3) treatment commute, (4) hospital barriers, (5) preventive health literacy. CONCLUSION: This study highlights the resilience and adherence of patients with nAMD in Denmark to their treatment despite various barriers. While the therapy may have negative effects on their well-being, patients do not opt out of treatment. These findings underscore the importance of personalised treatment plans that provide, for example, convenient access to care and clear future agreements at the hospital. By adopting more patient-centred approaches, healthcare providers can enhance patient satisfaction and improve treatment adherence, ultimately leading to better patient outcomes and quality of life.

VEGF Inhibition in Retinal Vein Occlusion Does Not Associate with Cardiovascular Morbidity or Mortality.

PURPOSE: Intravitreal treatment with VEGF inhibitors has proven safe in clinical trials, but often on selected patient groups and without statistical power to investigate rare safety events. Data on anti-VEGF treatment in patients with retinal vein occlusion (RVO) are sparsely represented, and studies providing population-based, long-term follow-up are needed to assess the risks in routine clinical practice. We aimed to evaluate the association between treatment with anti-VEGF and the risk of incident cardiovascular disease (CVD) and all-cause mortality in patients with RVO, and whether this association was affected by selected risk factors. DESIGN: A cohort study from January 2012 to December 2018 using Danish nationwide registries linked on an individual level. SUBJECTS: Patients with RVO (n = 7235), exposed (n = 3508), and unexposed (n = 3727) to anti-VEGF, aged ≥ 40 years, alive, and living in Denmark. METHODS: Cox proportional hazards analysis evaluating the effect of intravitreal VEGF inhibitory treatment on incident CVD and all-cause mortality. MAIN OUTCOME MEASURES: A predefined analysis plan specified primary outcomes as hazard ratios (HRs) of a composite CVD endpoint and all-cause mortality in patients treated with anti-VEGF compared with untreated. Secondary outcomes included cumulative dose analysis, HRs on subgroups of CVD, and stratified analyses evaluating the effect of sex, age, diabetes, intensive treatment, and preexisting CVD on the HRs. RESULTS: We found no increased risk of composite CVD (HR, 1.07; 95% confidence interval [CI], 0.89-1.29) or all-cause mortality (HR, 0.88; 95% CI, 0.77-1.00) in patients with RVO treated with anti-VEGF. In the secondary analyses, we found no dose-response relationship. We found an increased risk of intracranial hemorrhage (HR, 1.66; 95% CI, 1.02-2.71), but no increased risks in remaining subgroups of CVD. We found no increased risk associated with selected predisposing risk factors, and no increased risk in patients with preexisting CVD. CONCLUSION: Treatment with anti-VEGF in patients with RVO is safe, when evaluated in a nationwide, population-based setting. An increased risk of intracranial hemorrhage might be present, but cannot be reliably quantified and should be further elucidated by larger population-based studies including all indications for anti-VEGF treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Retinal artery occlusion does not act as an independent marker of upcoming dementia: results from a Danish 20-year cohort study.

PURPOSE: Retinal artery occlusion (RAO) is a vision threatening disease associated with cerebral vascular dysfunction, which may reflect initial signs of cerebral pathology. Early detection of patients in risk of dementia could allow for preventative treatment. Hence, this study aimed to investigate RAO as an independent biomarker of incident dementia. METHODS: This study was a nationwide, 20-year longitudinal cohort study in Denmark with inclusion from 1998 to 2020 and follow up until the end of 2022. We identified 2 205 159 individuals aged 65 or older through the Danish national health registers and monitored RAO (exposure) and dementia (outcome) status. We calculated incidence rate and performed a Cox regression analysis with hazard ratio (HR) and 95% confidence interval (CI) for RAO as a marker of dementia in a crude, a semi-adjusted (age and sex), and a fully adjusted model (furthermore adjusted for marital status and systemic comorbidity.) RESULTS: We identified 8 863 individuals with RAO. Incidence rates were higher among exposed compared to unexposed individuals (12.28 and 8.18 per 1000 person-years at risk, respectively). Individuals with RAO were more likely to be male and older at inclusion, to have hypertension, dyslipidaemia, cardiovascular disease, chronic kidney disease, and diabetes (p < 0.001). RAO was not associated with all-cause dementia in the crude analysis (HR 1.07 CI [1.00-1.17]) or in the fully adjusted analysis (HR 0.98 CI [0.91-1.06]. CONCLUSION: Although individuals with RAO had a higher incidence of dementia compared to unexposed individuals, these associations were lost when confounders were taken into account.

Retinal main vessel calibers and systemic markers for long-term development of proliferative diabetic retinopathy.

PURPOSE: To evaluate if retinal vascular calibers and systemic risk factors in patients with no or minimal diabetic retinopathy (DR) can predict risk of long-term progression to proliferative diabetic retinopathy (PDR). METHODS: This was a matched case-control study of patients with diabetes having no or minimal DR at baseline with (cases) or without (controls) subsequent development of PDR. We collected six-field, 45-degree retinal images, demographic and clinical data from the Funen Diabetes Database. RESULTS: We included 52 eyes from 39 cases and 107 eyes from 89 controls matched on sex, age, type of diabetes, time from first to last screening episode and baseline DR level. Cases had higher HbA1c (73 vs. 55 mmoL/moL; p < 0.001), triglycerides (1.32 vs. 1.16 mmoL/L; p = 0.02) and longer duration of diabetes (19 vs. 14 years; p = 0.01), but the groups did not differ in calibers of retinal arterioles (229 vs. 227 µm; p = 0.49), venules (289 vs. 290 µm; p = 0.83) or the arterio-to-venule ratio (0.78 vs. 0.77; p = 0.86).In a multivariable logistic regression model with cluster robust standard error, HbA1c (OR 1.54 per 10 mmoL/moL; 95%-CI: 1.15-2.07; p = 0.004), triglyceride (OR 1.39 per 1 mmoL/L; 95%-CI: 1.03-1.86; p = 0.03) and duration of diabetes (OR 1.09 per year; 95%-CI: 1.03-1.16; p = 0.003) were independent risk factors for PDR. CONCLUSION: Retinal vascular calibers did not predict long-term development of PDR in contrast to well-established risk factors like HbA1c, triglyceride and duration of diabetes.

Cardiovascular morbidity and all-cause mortality in patients with retinal vein occlusion: a Danish nationwide cohort study.

BACKGROUND/AIMS: Associations between retinal vein occlusion (RVO) and subsequent cardiovascular disease (CVD) or mortality have not been evaluated in a recent cohort, after novel therapeutic options have increased referrals for treatment of the condition. We aimed to evaluate overall and subtype-stratified risk of CVD and all-cause mortality following RVO and assess any alterations after the introduction of angiostatic therapy in Denmark in 2011. METHODS: This nationwide, registry-based cohort study from 1998 to 2018 evaluated 4 194 781 individuals. Hazard ratios (HRs) were reported for RVO as an overall measure and subclassified as branch and central RVO. RESULTS: Patients with RVO (n=15 665) were median 71.8 years old at the time of exposure and 50.7% were women. RVO associated with incident CVD (adjusted HR 1.13, 95% CI 1.09 to 1.17) but not mortality (adjusted HR 1.00, 95% CI 0.97 to 1.03). Almost similar risks of CVD were found for patients with branch and central RVO (adjusted HRs 1.14, 95% CI 1.03 to 1.25, and 1.12, 95% CI 1.00 to 1.25, respectively), but only patients with central RVO exhibited increased mortality (adjusted HR 1.12, 95% CI 1.04 to 1.21). Risk of CVD, especially non-ischaemic, was higher for patients diagnosed after 2011 (adjusted HRs 1.24, 95% CI 1.15 to 1.33 vs 1.06, 95% CI 1.01 to 1.12). CONCLUSION: In a cohort of the Danish population aged 40 years or more, patients with RVO had a 13% increased risk of incident CVD compared with unexposed individuals. Risk of CVD was increased after 2011, when intravitreal angiostatic treatment was introduced and referral practices altered.

Prayer and meditation practices in the early COVID-19 pandemic: A nationwide survey among Danish pregnant women. The COVIDPregDK study.

BACKGROUND: The emergence of the COVID-19 pandemic and the derived changes in maternity care have created stress and anxiety among pregnant women in different parts of the world. In times of stress and crisis, spirituality, including spiritual and religious practices, may increase. OBJECTIVE: To describe if the COVID-19 pandemic influenced pregnant women's considerations and practises of existential meaning-making and to investigate such considerations and practices during the early pandemic in a large nationwide sample. METHODS: We used survey data from a nationwide cross-sectional study sent to all registered pregnant women in Denmark during April and May 2020. We used questions from four core items on prayer and meditation practices. RESULTS: A total of 30,995 women were invited, of whom 16,380 participated (53%). Among respondents, we found that 44% considered themselves believers, 29% confirmed a specific form of prayer, and 18% confirmed a specific form of meditation. In addition, most respondents (88%) reported that the COVID-19 pandemic had not influenced their responses. CONCLUSION: In a nationwide Danish cohort of pregnant women, existential meaning-making considerations and practices were not changed due to the COVID-19 pandemic. Nearly one in two study participants described themselves as believers, and many practised prayer and/or meditation.

Retinal vein occlusion as an age-dependent marker of incident dementia in a long-term Danish national cohort.

PURPOSE: The aim of this study was to investigate retinal vein occlusion (RVO) as an independent marker of incident dementia. METHODS: In a prospective nationwide cohort study, we identified 2 225 568 individuals through the Danish national health registers. Individuals older than 65 years, without unspecified retinal vascular occlusion or dementia were included from 1998 to 2020 and followed until 2022. We calculated the incidence rate (IR) and performed a Cox regression analysis with a hazard ratio (HR) and 95% confidence interval (CI) for RVO (exposure) as a marker of all-cause dementia adjusted for systemic comorbidity. RESULTS: We identified 19 669 individuals with RVO who had a higher prevalence of systemic comorbidity at inclusion compared to those without RVO (n = 2 185 483). We performed a Cox regression analysis for age-dependent exposure due to non-proportional hazards in the pre-planned analysis. Exposed individuals younger than 75 years had an increased risk of all-cause dementia (adjusted HR 1.09, 95% CI 1.01-1.18), whereas individuals older than 75 years had a decreased risk of all-cause dementia (adjusted HR 0.92, 95% CI 0.86-0.98). CONCLUSION: Individuals with RVO had an age-dependent risk of dementia, with a 9% increased risk in individuals with RVO younger than 75 years and an 8% decreased risk in individuals older than 75 years at the time of exposure.

Diabetic retinopathy is a predictor of chronic respiratory failure: A nationwide register-based cohort study.

Purpose: Diabetic retinopathy (DR) is a hypoxic retinal disease, but so far, the association with systemic hypoxia is poorly understood. Hence, the aim of this study was to evaluate cross-sectional and longitudinal associations between DR and chronic respiratory failure (CRF) in a national cohort. Design: Cross-sectional and 5-year longitudinal register-based cohort study. Methods: Between 2013 and 2018, we included patients with diabetes from the Danish Registry of Diabetic Retinopathy, who were each age and sex matched with five controls without diabetes. At index date, the prevalence of CRF was compared between cases and controls, and the longitudinal relationship between DR and CRF was assessed in a five-year follow-up. Results: At baseline, we identified 1,980 and 9,990 patients with CRF among 205,970 cases and 1,003,170 controls. The prevalence of CRF was higher among cases than controls (OR 1.75, 95% CI 1.65-1.86), but no difference between cases with and without DR was found.During follow-up, we identified 1,726 and 5,177 events of CRF among cases and controls, respectively. The incidence of CRF was higher among both cases with and without DR compared to controls (DR level 0: HR 1.24, 95% CI 1.16-1.33, DR level 1-4: HR 1.86, 95% CI 1.63-2.12), and higher among cases with DR compared to cases without DR (HR 1.54, 95% CI 1.38-1.72). Conclusion: In this study based on nationwide data, we found an increased risk of present and incident CRF in patients with diabetes with or without DR, and we identified DR as a predictor of future CRF.

Longitudinal bidirectional associations between diabetic retinopathy and diagnosed depression: Results from a Danish nationwide registry-based cohort study.

OBJECTIVE: Diabetic retinopathy (DR) is a feared complication and a leading course of visual impairment, but the connection between DR and depression including the direction has never been studied in a nationwide cohort. We aimed to assess, whether the associations between DR and diagnosed depression are bidirectional. METHODS: We performed a national register-based cohort study of individuals with type 2 diabetes, who attended diabetic eye screening between January 2013 and June 2022. Level of DR was extracted from the Danish Registry of Diabetic Retinopathy. The severity of DR was assessed according to the International Clinical Diabetic Retinopathy severity scale. Diagnosed depression was ascertained by physician diagnostic codes of unipolar depression (F32), recurrent depression (F33) or dysthymia (F34.1) from the Danish National Patient Register. We estimated presence of diagnosed depression according to DR level at index date and risk of diagnosed depression during follow-up using multivariable logistic and Cox regression, respectively. Secondly, we assessed whether diagnosed depression at index date could predict incident DR. RESULTS: We included 240,893 individuals with type 2 diabetes with baseline rates of diagnosed depression ranging from 5.2 to 6.0 % for DR level 1-4. At index date, individuals with type 2 diabetes and DR were less likely to have a history of diagnosed depression (multivariable adjusted OR, 0.77 [95 % CI 0.73-0.82]). In 226,523 individuals with type 2 diabetes followed for 1,159,755 person-years, 1.7 % developed at least one episode of diagnosed depression. In a model adjusted for age and sex, individuals with DR at index date had an increased risk of incident diagnosed depression compared to those without DR (HR 1.25 [95 % CI 1.16-1.36]). Adjusting for marital status, use of glucose-, lipid- and blood pressure lowering medication, HbA1c, diabetic neuropathy and Charlson comorbidity index waived the above risk (multivariable adjusted HR 1.02 [95 % CI 0.93-1.12]). Furthermore a previous history of diagnosed depression was not associated with increased risk of incident DR (multivariable adjusted HR 0.89 [95 % CI 0.77-1.03]). CONCLUSION: In this nationwide cohort study, individuals with DR at first screening were 23 % less likely to have a history of depression, but our data did not support a bidirectional association between DR and depression. Selection bias may have occurred as diagnosed depression is a known barrier for attending DR-screening.

Bariatric surgery in individuals with type 2 diabetes is not associated with short or long-term risk of diabetic retinopathy progression: results from a nationwide cohort study.

AIMS: Bariatric surgery is used to induce weight loss and glycemic stability in type 2 diabetes (T2D). It has been a concern that this may lead to early worsening of diabetic retinopathy (DR) due to a rapid decline in HbA1c. In this study, we evaluated the risk of short and long-term DR development and need for ocular intervention in an entire nation of individuals with T2D undergoing bariatric surgery. METHODS: The study comprised a national, register-based cohort of individuals with T2D screened for DR. Cases were matched by age, sex and DR level at the date of surgery (index date) with non-bariatric controls. We extracted information on DR levels, in- and outpatient treatments, pharmaceutical prescriptions and laboratory values. We evaluated worsening of DR (incident and progressive DR) at follow-up (6 and 36 months). RESULTS: Amongst 238,967 individuals with T2D, who attended diabetic eye screening, we identified 553 that underwent bariatric surgery (0.2%) and 2677 non-bariatric controls. Median age was 49 years, and 63% were female. Cases had more comorbidities, lower HbA1c as well as more frequent use of glucose-lowering and antihypertensive medication than controls at index date. In a fully adjusted logistic regression model, the risk of DR worsening for cases was not significantly different compared to controls, neither short-term (OR 0.41 [CI 95% 0.13; 1.33], p = 0.14) nor long-term (OR 0.64 [CI 95% 0.33; 1.24], p = 0.18). CONCLUSIONS: In this nationwide study, bariatric surgery did not associate with increased risk of short- or long-term DR worsening.