Association between Glucagon-like Peptide-1 Receptor Agonists and the Risk of Glaucoma in Individuals with Type 2 Diabetes.

PURPOSE: To examine the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and the development of glaucoma in individuals with type 2 diabetes. DESIGN: Nationwide, nested case-control study. PARTICIPANTS: From a nationwide cohort of 264 708 individuals, we identified 1737 incident glaucoma cases and matched them to 8685 glaucoma-free controls, all aged more than 21 years and treated with metformin and a second-line antihyperglycemic drug formulation, with no history of glaucoma, eye trauma, or eye surgery. METHODS: Cases were incidence-density-matched to 5 controls by birth year, sex, and date of second-line treatment initiation. MAIN OUTCOME MEASURES: Conditional logistic regression was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for glaucoma, defined by first-time diagnosis, first-time use of glaucoma-specific medication, or first-time glaucoma-specific surgical intervention. RESULTS: Compared with the reference group, who received treatments other than GLP-1RA, individuals who were exposed to GLP-1RA treatment exhibited a lower risk of incident glaucoma (HR, 0.81; CI, 0.70-0.94; P = 0.006). Prolonged treatment extending beyond 3 years lowered the risk even further (HR, 0.71; CI, 0.55-0.91; P = 0.007). Treatment with GLP-1RA for 0 to 1 year (HR, 0.89; CI, 0.70-1.14; P = 0.35) and 1 to 3 years (HR, 0.85; CI, 0.67-1.06; P = 0.15) was not significant. CONCLUSIONS: Exposure to GLP-1RA was associated with a lower risk of developing glaucoma compared with receiving other second-line antihyperglycemic medication. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

The prognosis following amphetamine poisoning.

AIMS: This study investigated the long-term mortality following poisoning by amphetamine or substituted amphetamines. Furthermore, we examined the social problems and somatic and psychiatric co-morbidity related to amphetamine poisoning, and their impact on the long-term survival. METHODS: We identified amphetamine poisoned patients from the Danish Poison Information Centre database and correlated their personal identification numbers with seven Danish national registries related to different social and health aspects. For each case, we sampled 100 age and gender matched controls from the background population. RESULTS: From August 2006 to December 2013 we identified 1444 patients (70% males) who experienced amphetamine poisoning; 52% of the cases were classified as mixed poisonings and the average age at first contact was 24.8 years (SD 8.6). The prevalence of psychiatric disorders, HIV, viral hepatitis, and previous prison incarceration was approximately 10 times higher than among healthy controls. After seven years 11% were deceased as opposed to 0.6% in the control group, and 64% of the patients died from unnatural causes. Male gender (HR 2.29, 95% CI (1.07-4.90)), age (HR 1.06, 95% CI (1.03-1.09)), opioid dependence (HR 2.88, 95% CI (1.42-5.85)), schizophrenia (HR 3.09,95% CI (1.63-5.86)), affective disorders (HR 2.65, 95% CI (1.44-4.90)) and HIV (HR 5.45, 95% CI (1.19-24.90)) were associated with a high mortality. Furthermore, a significant proportion of these patients experienced social and health related deterioration in the years following poisoning. CONCLUSIONS: Amphetamine poisoning is associated with a poor long-term prognosis and is complicated by additional social and health related issues.

Screening for celiac disease in Danish adults.

OBJECTIVE: The prevalence of celiac disease (CD) as recorded in the Danish National Patient Registry is ∼50/100,000 persons. This is much lower than the reported prevalence of CD in other Nordic countries and underdiagnosis is suspected. Our aim was to estimate the prevalence of CD in a population-based study of Danish adults. METHODS: A total of 2297 adults aged 24-76 years living in the southwestern part of Copenhagen were screened for CD by immunoglobulin (Ig)A and IgG antibodies to transglutaminases and deamidated gliadin. IgA/IgG-positive participants were invited to a clinical evaluation, including biopsies, by a gastroenterologist. RESULTS: Of the invited 56 participants, 40 underwent a full clinical evaluation and 8 persons were diagnosed with CD; 2 of the 16 persons, who did not complete the clinical evaluation, were considered by experts to have probable CD. None of the above 56 participants had a known history of CD or a recorded diagnosis of CD in National Patient Registry. By combining cases of biopsy-proven CD (n = 8), probable CD (n = 2), and registry-recorded CD (n = 1), the prevalence of CD was estimated to be 479/100,000 (11/2297) persons (95% CI: 197-761). CONCLUSION: In this general adult population, the prevalence of CD as estimated by screening and clinical evaluation was 10 times higher than the registry-based prevalence of CD. Of 11 participants diagnosed with CD in our screening study, 10 were unaware of the diagnosis prior to the study. Thus, our study suggests that CD is markedly underdiagnosed in Danish adults.

Politics and policies.

BACKGROUND: In 2003 major reforms of the public pension system in Denmark were implemented. The aim was to reduce the number of early retirees. Focus was changed from limitations to abilities and flexible jobs (flex-jobs) were introduced. However, the criteria for invalidity pensions (IP) in the private sector remained unchanged according to the policies. The aim of this study was to analyze the incidence of IP in a member owned pension fund-before and after the pension reforms. Furthermore we analyzed the distribution of diagnoses that led to IP and with which mortality these were related. MATERIALS AND METHODS: A prospective design was used. All the applications for IP in Finanssektorens Pensionskasse (FSP) in the period from January 1, 1997 to May 1, 2009 were registered continuously. In total, 317 persons were granted IP. RESULTS: Thirty percent of payouts were related psychiatric disorders, 18% were due to cancer and 52% to other somatic disorders. The mortality for cancer patients was significantly higher than those with other diagnoses. The incidence of IP in FSP was about one third compared to the background population. The incidence of IP peaked in 2001 and 2007 to 2009. DISCUSSION AND CONCLUSION: We were not able to detect any positive effects from the pension reform, and this corresponds with studies from the Danish public sector. The Danish pension reform was unsuccessful in reducing the number of early retirees, and created a new government supported group of flex-jobber. Future reforms need to coordinate politics and policies.

Risk of Central Serous Chorioretinopathy in Male Androgen Abusers.

INTRODUCTION: Male gender is an important risk factor of central serous chorioretinopathy (CSC), and studies have explored the pathophysiological role of androgens in CSC with conflicting results. In this study, we shed light on this hot topic by exploring the risk of CSC in a large cohort of male androgen abusers. METHODS: This study included male androgen abusers identified through a nationwide anti-doping test program across Danish fitness centers from January 3 2006 to March 1 2018. For each case, we randomly sampled ten male controls using Danish nationwide registries. These controls were matched in age and date. Cases and controls were followed until May 16 2018. Data on diagnoses were extracted using the Danish National Registry of Patients using ICD-10 codes to identify cases with CSC. RESULTS: We included 1189 cases and 11,890 controls. Mean age at the time of doping sentence was 27.4 ± 6.9 years, and mean length of follow-up was 15.8 ± 3.6 years. We identified no cases of CSC in androgen abusers, and five cases of CSC in the control cohort. The difference between groups was not statistically significant (P = 1.0). CONCLUSIONS: Male androgen abusers were not at increased risk of CSC. Considering the lack of any signal in this large study, we speculate that if male androgen plays any direct role in the pathophysiology of CSC, its role may be subtle at best.

Inferring glaucoma status from prescriptions, diagnoses, and operations data: A Danish nationwide study.

PURPOSE: To assess a new method for inferring glaucoma status using prescriptions data. METHODS: The study population comprised all individuals living in Denmark in the period 1995 to 2018 and included 6,930,571 individuals. We used information from The National Prescription Registry on claimed prescriptions as the basis for our study (N = 223,592). We inferred glaucoma status using data on claimed prescriptions, in-hospital ICD-10 diagnoses, and in-hospital glaucoma surgeries. We infer glaucoma status in three ways using the prescription pattern: glaucoma inferred by (i) the use of a first claimed prescription, (ii) the use of a second claimed prescription with a gap of at least 90 days, and (iii) the use of a third claimed prescription for glaucoma medication, again with a gap of at least 90 days between prescriptions. Furthermore, we compared the results with alternative indications for glaucoma, namely in-hospital ICD-10-diagnosed glaucoma and in-hospital glaucoma surgery. RESULTS: We first determined that glaucoma status could be inferred from claimed prescription data and found that a single claimed prescription was highly correlated with the more restricted composite measure of glaucoma (R2 = 0.80, p <0.0001), with a kappa coefficient of 80%. Focusing on individuals with a confirmed in-hospital glaucoma diagnosis, we found a high sensitivity of 88% using anti-glaucomatous prescriptions as a surrogate marker for primary open-angle glaucoma (POAG). We then derived several descriptive insights. The prevalence of glaucoma increased during the period from 1996 to 2018, while the incidence was constant. We also found a decreasing trend in the ratio of the number of people diagnosed annually in hospitals to the number of people filling prescriptions. This indicated a relative increase in the number of patients treated or managed in the secondary sector. Finally, using data on diagnoses and claimed prescriptions, we found that the proportion of total noncompliant patients, i.e., patients who do not claim their prescription at any time in the study period (two decades) was at most 11.8%. This share is calculated on the basis of diagnosed patients who did not have surgery. The results was not sensitive to the glaucoma inference rule. CONCLUSION: Anti-glaucomatous medicine prescriptions can be used to infer glaucoma status, with useful implications for epidemiological research. The sensitivity is particularly high for primary open-angle glaucoma (POAG).

Glucagon-Like Peptide 1 Receptor Agonists - Potential Game Changers in the Treatment of Glaucoma?

Glaucoma is a common ocular neurodegenerative disease characterized by the progressive loss of retinal ganglion cells and their axons. It is the most common cause of irreversible blindness. With an increasing number of glaucoma patients and disease progression despite treatment, it is paramount to develop new and effective therapeutics. Emerging new candidates are the receptor agonists of the incretin hormone glucagon-like-peptide-1 (GLP-1), originally used for the treatment of diabetes. GLP-1 receptor (GLP-1R) agonists have shown neuroprotective effects in preclinical and clinical studies on neurodegenerative diseases in both the brain (e.g., Alzheimer's disease, Parkinson's disease, stroke and diabetic neuropathy) and the eye (e.g., diabetic retinopathy and AMD). However, there are currently very few studies investigating the protective effects of GLP-1R agonists in the treatment of specifically glaucoma. Based on a literature search on PubMed, the Cochrane Library, and ClinicalTrials.gov, this review aims to summarize current clinical literature on GLP-1 receptor agonists in the treatment of neurodegenerative diseases to elucidate their potential in future anti-glaucomatous treatment strategies.

Male Fertility Before and After Androgen Abuse.

PURPOSE: Previous research has found that male users of androgens are diagnosed approximately twice as often with infertility. We therefore set out to investigate the fertility in men using androgens. METHODS: The study included 545 males who tested positive for androgens in an anti-doping test program in Danish fitness centers during the period from January 3, 2006, to March 1, 2018. The confirmed androgen users were matched by birth year with 5450 male controls. We followed this cohort from 10 years prior to testing positive until the end of follow-up in May 2018. RESULTS: During the 10-year period prior to testing positive, the group of androgen users experienced a 26% lower fertility rate than the controls (rate ratio [RR] 0.74; 95% CI, 0.60-0.90; P = 0.0028). However, in the years following the doping sanction, they made a significant catch-up, and at completed follow-up the total fertility rate was only 7% lower than expected (RR 0.93, 95% CI, 0.84-1.03). The prevalence of assisted reproduction was 5.69% in the group of androgen users and 5.28% in the control group (P = 0.69). CONCLUSION: Androgen use was associated with a temporary decline in fertility and most androgen users achieved parenthood without any help from the health care system. Overall, the fertility rate and the prevalence of assisted reproduction among androgen users were close to those in the background population.

Brain Responses to Passive Sensory Stimulation Correlate With Intelligence.

This study investigates the association between intelligence and brain power responses to a passive audiovisual stimulation. We measure the power of gamma-range steady-state responses (SSRs) as well as intelligence and other aspects of neurocognitive function in 40 healthy males born in 1953. The participants are a part of a Danish birth cohort study and the data therefore include additional information measured earlier in life. Our main power measure is the difference in power between a visual stimulation and a combined audiovisual stimulation. We hypothesize and establish empirically that the power measure is associated with intelligence. In particular, we find a highly significant correlation between the power measure and present intelligence scores. The association is robust to controlling for size-at-birth measures, length of education, speed of processing as well as a range of other potentially confounding factors. Interestingly, we find that intelligence scores measured earlier in life (childhood, youth, late midlife), are also correlated with the present-day power measure, suggesting a deep connection between intelligence and the power measure. Finally, we find that the power measure has a high sensitivity for detection of an intelligence score below the average.

EEG correlates of visual short-term memory in older age vary with adult lifespan cognitive development.

Visual short-term memory (vSTM) is a cognitive resource that declines with age. This study investigated whether electroencephalography (EEG) correlates of vSTM vary with cognitive development over individuals' lifespan. We measured vSTM performance and EEG in a lateralized whole-report task in a healthy birth cohort, whose cognitive function (intelligence quotient) was assessed in youth and late-middle age. Higher vSTM capacity (K; measured by Bundesen's theory of visual attention) was associated with higher amplitudes of the contralateral delay activity (CDA) and the central positivity (CP). In addition, rightward hemifield asymmetry of vSTM (Kλ) was associated with lower CDA amplitudes. Furthermore, more severe cognitive decline from young adulthood to late-middle age predicted higher CDA amplitudes, and the relationship between K and the CDA was less reliable in individuals who show higher levels of cognitive decline compared to individuals with preserved abilities. By contrast, there was no significant effect of lifespan cognitive changes on the CP or the relationship between behavioral measures of vSTM and the CP. Neither the CDA, nor the CP, nor the relationships between K or Kλ and the event-related potentials were predicted by individuals' current cognitive status. Together, our findings indicate complex age-related changes in processes underlying behavioral and EEG measures of vSTM and suggest that the K-CDA relationship might be a marker of cognitive lifespan trajectories.

Passive Double-Sensory Evoked Coherence Correlates with Long-Term Memory Capacity.

HIGHLIGHTS Memory correlates with the difference between single and double-sensory evoked steady-state coherence in the gamma range (ΔC).The correlation is most pronounced for the anterior brain region (ΔCA ).The correlation is not driven by birth size, education, speed of processing, or intelligence.The sensitivity of ΔCA for detecting low memory capacity is 90%. Cerebral rhythmic activity and oscillations are important pathways of communication between cortical cell assemblies and may be key factors in memory. We asked whether memory performance is related to gamma coherence in a non-task sensory steady-state stimulation. We investigated 40 healthy males born in 1953 who were part of a Danish birth cohort study. Coherence was measured in the gamma range in response to a single-sensory visual stimulation (36 Hz) and a double-sensory combined audiovisual stimulation (auditive: 40 Hz; visual: 36 Hz). The individual difference in coherence (ΔC) between the bimodal and monomodal stimulation was calculated for each subject and used as the main explanatory variable. ΔC in total brain were significantly negatively correlated with long-term verbal recall. This correlation was pronounced for the anterior region. In addition, the correlation between ΔC and long-term memory was robust when controlling for working memory, as well as a wide range of potentially confounding factors, including intelligence, length of education, speed of processing, visual attention and executive function. Moreover, we found that the difference in anterior coherence (ΔCA ) is a better predictor of memory than power in multivariate models. The sensitivity of ΔCA for detecting low memory capacity is 92%. Finally, ΔCA was also associated with other types of memory: verbal learning, visual recognition, and spatial memory, and these additional correlations were also robust enough to control for a range of potentially confounding factors. Thus, the ΔC is a predictor of memory performance may be useful in cognitive neuropsychological testing.

Antihypertensive Medication Postpones the Onset of Glaucoma: Evidence From a Nationwide Study.

The aim was to investigate the impact of antihypertensive medication on the onset of glaucoma. Data from the complete Danish population between 40 and 95 years of age were used in the period from 1996 to 2012, covering >2.6 million individuals. The National Danish Registry of Medicinal Products Statistics was used to identify all claimed prescriptions for glaucoma medication and antihypertensive drugs. We first investigated basic correlations in the data and found that patients treated with antihypertensive medication, at any time during the study period, had a significantly higher overall relative risk (RR) of glaucoma, even when controlling for age and sex (with a RR of 1.31 and P<0.0001). Furthermore, our data confirm the well-known positive association between age and glaucoma. To investigate the causal effect of antihypertensive treatment on the onset of treatment for glaucoma, we used a regression discontinuity study design. This analysis provides our main finding, namely that prescription of antihypertensive medication leads to a significant reduction in the risk of developing glaucoma. Therefore, although hypertension-as indicated by the use of antihypertensive medication-is positively correlated with glaucoma, our study indicates that antihypertensive medication itself may have a preventive effect on the development of glaucoma.

Visual steady state in relation to age and cognitive function.

Neocortical gamma activity is crucial for sensory perception and cognition. This study examines the value of using non-task stimulation-induced EEG oscillations to predict cognitive status in a birth cohort of healthy Danish males (Metropolit) with varying cognitive ability. In particular, we examine the steady-state VEP power response (SSVEP-PR) in the alpha (8Hz) and gamma (36Hz) bands in 54 males (avg. age: 62.0 years) and compare these with 10 young healthy participants (avg. age 27.6 years). Furthermore, we correlate the individual alpha-to-gamma difference in relative visual-area power (ΔRV) with cognitive scores for the older adults. We find that ΔRV decrease with age by just over one standard deviation when comparing young with old participants (p<0.01). Furthermore, intelligence is significantly negatively correlated with ΔRV in the older adult cohort, even when processing speed, global cognition, executive function, memory, and education (p<0.05). In our preferred specification, an increase in ΔRV of one standard deviation is associated with a reduction in intelligence of 48% of a standard deviation (p<0.01). Finally, we conclude that the difference in cerebral rhythmic activity between the alpha and gamma bands is associated with age and cognitive status, and that ΔRV therefore provide a non-subjective clinical tool with which to examine cognitive status in old age.

Danish Nationwide Data Reveal a Link between Diabetes Mellitus, Diabetic Retinopathy, and Glaucoma.

Aims. To determine the association between treatment against diabetes mellitus (DM) and treatment with antiglaucomatous drugs in the entire Danish population and to investigate the comorbidity between DM and its complications with antiglaucomatous treatment. Methods. Retrospective nationwide cohort study with data over a 16-year follow-up period. The National Danish Registry of Medicinal Products Statistics was used to identify all claimed prescriptions for antiglaucomatous medication and DM drugs. ICD-10 classifications were furthermore used to identify comorbidities between antiglaucomatous medication and the DM complications, diabetic retinopathy (DR), and nephropathy. Results. A total of 6,343,747 individuals in the period between 1996 and 2012 were analyzed. The overall incidence rate of new-onset glaucoma patients was 0.07 per 1000 person-years for the reference population compared to 36 per 1000 person-years for all diagnosed DM cases. Patients treated with DM drugs had about two times higher relative risk of glaucoma, when adjusting for a range of factors. The presence of DR alone or in combination with nephropathy increased the risk of glaucoma. Conclusions. The present study reports a strong association between DM and onset of glaucoma treatment in the entire Danish population.

The Prevalence and Incidence of Glaucoma in Denmark in a Fifteen Year Period: A Nationwide Study.

PURPOSE: The purpose of the present study was to describe the prevalence, incidence and geographic variation of glaucoma in Denmark in the period from 1996 to 2011. Moreover, the aim was to identify the treatment patterns of glaucoma within the studied period. METHODS: All Danish citizens were included throughout the study period. The National Prescription Registry was used to identify all claimed prescriptions for glaucoma medication. RESULTS: A total of 116,592 incident glaucoma patients were identified. Average age at onset was 66 years (range: 0-105 years), 55% were women. The prevalence of glaucoma increased from 0.79% to 1.72% during the investigated period. In 2011 glaucoma affected 3.76% of the population above 50 years and 10% in patients above 80 years. The age-specific incidence rate of glaucoma seemed to be constant and the increasing prevalence was primarily attributed to an aging population. We found the highest prevalence of glaucoma in the capital region of Denmark. Within the studied period the use of prostaglandin analogs and combination drugs increased, whereas the use of ß-blockers, carbon anhydrase inhibitors and parasympathomimetic drugs decreased (p<0.001). Finally, the use of α2-adrenergic agonists remained unchanged. A total of 75% of the patients were treated with two or more glaucoma medications. CONCLUSIONS: Over all, the present study is the first to assess the frequency and the development of glaucoma in Denmark over a 15-year period. We find that glaucoma affects a little less than 2% of the total population and increases with age to reach a prevalence of more than 10% amongst people above 80 years. Generally, the present study is the largest nation-wide study ever made and must be a close-to-real-life-picture of the utilization of glaucoma medication on a national scale. Our findings confirm other recent estimations on an increasing burden of glaucoma globally.

[Patient information leaflets seen through the eyes of patients in a general practice]. / Patienters vurdering af medicinpakningernes indlaegssedler.

INTRODUCTION: The objective was to investigate patients' perception of patient information leaflets, including their readability, comprehensibility and their impact on adherence. MATERIAL AND METHODS: A 14-item questionnaire was prepared and answered by unselected patients in a general practice in Copenhagen. RESULTS: A total of 111 patients were included. Eighty-eight patients (79%) always or often read the patient information leaflets. Among these, 77% attached importance to adverse effects. A mere 13% attached importance to all leaflet information. In all, 21% never or rarely read patient information leaflets, but relied on the doctor or the pharmacist. 62% of the interviewed had no problems reading or understanding the patient information leaflets. Among the 38% with reading problems, 57% had difficulties due to text-size, and 33% found the written language difficult to understand. Thirty-five patients (32%) stated that they had stopped taking medication due to the information about adverse effects. CONCLUSION: The patient information leaflet is an important source of drug information as most patients read the leaflet and nearly a third of the patients stated that information about the adverse effects had made them stop taking their medicine. Future studies should bring into focus the reason for medication adherence, how written information can be made easier to read, comprehensive and correct without contributing to anxiety and non-adherence.