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ackground Type 2 diabetes (T2D) treatment has changed markedly within the last decades. We aimed to explore whether people with severe mental illness (SMI) have followed the same changes in T2D treatment as those without SMI, as multiple studies suggest that people with SMI receive suboptimal care for somatic disorders. Methods In this registry-based annual cohort study, we explored the T2D treatment from 2001 to 2015 provided in general practices of the Greater Copenhagen area. We stratified the T2D cohorts by their pre-existing SMI status. T2D was defined based on elevated glycated hemoglobin (≥48 mmol/mol) or glucose (≥11 mmol/L) using data from the Copenhagen Primary Care Laboratory Database. Individuals with schizophrenia spectrum disorders (ICD-10 F20–29) or affective disorders (bipolar disorder or unipolar depression, ICD-10 F30–33) were identified based on hospital-acquired diagnoses made within 5 years before January 1 each year for people with prevalent T2D or 5 years before meeting our T2D definition for incident patients. For comparison, we defined a non-SMI group, including people who did not have a hospital-acquired diagnosis of schizophrenia spectrum disorders, affective disorders, or personality disorders. For each calendar year, we assembled cohorts of people with T2D with or without SMI. We used Poisson regression to calculate the rates per 100 person-years of having at least one biochemical test (glycated hemoglobin, low-density lipoprotein cholesterol, estimated glomerular filtration rate, and urine albumin-creatinine ratio), having poor control of these biochemical results, taking glucose-lowering or cardiovascular medications, or experiencing a clinical outcome, including all-cause mortality and cardiovascular mortality. Three outcomes (cardiovascular events, cardiovascular mortality, and all-cause mortality) were additionally examined and adjusted for age and sex in a post hoc analysis. Results From 2001 to 2015, Background: Type 2 diabetes (T2D) treatment has changed markedly within the last decades. We aimed to explore whether people with severe mental illness (SMI) have followed the same changes in T2D treatment as those without SMI, as multiple studies suggest that people with SMI receive suboptimal care for somatic disorders. Methods: In this registry-based annual cohort study, we explored the T2D treatment from 2001 to 2015 provided in general practices of the Greater Copenhagen area. We stratified the T2D cohorts by their pre-existing SMI status. T2D was defined based on elevated glycated hemoglobin (≥48 mmol/mol) or glucose (≥11 mmol/L) using data from the Copenhagen Primary Care Laboratory Database. Individuals with schizophrenia spectrum disorders (ICD-10 F20–29) or affective disorders (bipolar disorder or unipolar depression, ICD-10 F30–33) were identified based on hospital-acquired diagnoses made within 5 years before January 1 each year for people with prevalent T2D or 5 years before meeting our T2D definition for incident patients. For comparison, we defined a non-SMI group, including people who did not have a hospital-acquired diagnosis of schizophrenia spectrum disorders, affective disorders, or personality disorders. For each calendar year, we assembled cohorts of people with T2D with or without SMI. We used Poisson regression to calculate the rates per 100 person-years of having at least one biochemical test (glycated hemoglobin, low-density lipoprotein cholesterol, estimated glomerular filtration rate, and urine albumin-creatinine ratio), having poor control of these biochemical results, taking glucose-lowering or cardiovascular medications, or experiencing a clinical outcome, including all-cause mortality and cardiovascular mortality. Three outcomes (cardiovascular events, cardiovascular mortality, and all-cause mortality) were additionally examined and adjusted for age and sex in a post hoc analysis. Results: From 2001 to 2015, 66,914 individuals were

Objective To evaluate the risk of falls and fractures in users of benzodiazepines, Z-drugs, or melatonin. Methods We followed 699,335 adults with a purchase of benzodiazepines, Z-drugs, or melatonin in the Danish National Prescription Registry between 2003 and 2016 for falls and fractures in the Danish National Patient Registry between 2000 and 2018. A self-controlled case-series analysis and conditional Poisson regression were used to derive incidence rate ratios (IRR) of falls and fractures during six predefined periods. Results In total 62,105 and 36,808 adults, respectively, experienced a fall or fracture. For older adults, the risk of falls was highest during the 3-month pre-treatment period (IRRmen+70, 4.22 (95% confidence interval, 3.53–5.05), IRRwomen + 70, 3.03 (2.59–3.55)) compared to the baseline (>1 year before initiation). The risk continued to be higher in the later treatment periods. Contrarily, in men and women aged 40–69 years, the risk was only higher in the 3-month pre-treatment period. The incidence of falls among young men and women was slightly lower after initiation of sedating medication (treatment period, IRRmen15–39, 0.66 (0.50–0.86), IRRwomen15–39, 0.65 (0.51–0.83)). Analyses with fractures as outcome yielded similar results. Conclusions Although falls and fractures occur more often in persons using sedative-hypnotic medication, the higher risk of falls and fractures in the pre-treatment period relative to the period directly after treatment, suggests that this association is better explained by other factors that elicited the prescription of this medication rather than the adverse effects of the sedative-hypnotic medication., Objective: To evaluate the risk of falls and fractures in users of benzodiazepines, Z-drugs, or melatonin. Methods: We followed 699,335 adults with a purchase of benzodiazepines, Z-drugs, or melatonin in the Danish National Prescription Registry between 2003 and 2016 for falls and fractures in the Danish National Patient Registry between 2000 and 2018. A self-controlled case-series analysis and conditional Poisson regression were used to derive incidence rate ratios (IRR) of falls and fractures during six predefined periods. Results: In total 62,105 and 36,808 adults, respectively, experienced a fall or fracture. For older adults, the risk of falls was highest during the 3-month pre-treatment period (IRRmen+70, 4.22 (95% confidence interval, 3.53–5.05), IRRwomen + 70, 3.03 (2.59–3.55)) compared to the baseline (>1 year before initiation). The risk continued to be higher in the later treatment periods. Contrarily, in men and women aged 40–69 years, the risk was only higher in the 3-month pre-treatment period. The incidence of falls among young men and women was slightly lower after initiation of sedating medication (treatment period, IRRmen15–39, 0.66 (0.50–0.86), IRRwomen15–39, 0.65 (0.51–0.83)). Analyses with fractures as outcome yielded similar results. Conclusions: Although falls and fractures occur more often in persons using sedative-hypnotic medication, the higher risk of falls and fractures in the pre-treatment period relative to the period directly after treatment, suggests that this association is better explained by other factors that elicited the prescription of this medication rather than the adverse effects of the sedative-hypnotic medication.

Purpose of review Elevated serum low-density lipoprotein cholesterol (LDL-C) levels at middle-age constitute a strong risk factor for later cardiovascular events. In older populations, however, LDL-C levels are no longer predictive of cardiovascular mortality or may even seem protective. Whether the altered risk pattern of LDL-C in old age reflects a causal mechanism or is due to confounding and bias is subject to debate. In this review, we briefly discuss the possible explanations for the altered risk pattern of LDL-C observed in old age. Recent findings Using examples from the recent literature we illustrate how LDL-C levels ‘lose’ their predictive value as a cardiovascular risk factor in old age. We review three potential explanations for the changed cardiovascular risk pattern of LDL-C in older populations: survivorship bias, reverse causation, and effect modification. Summary The absent or protective effect of LDL-C on cardiovascular mortality in older populations found in observational studies might be explained by survivorship bias, reverse causation, and effect modification. However, this does not necessarily preclude the possibility that (specific) cholesterol-lowering treatment could decrease the risk of morbidity and mortality. Placebo-controlled trials may importantly add to our understanding of who may benefit from lipid-lowering therapy or statins at an older age., Purpose of reviewElevated serum low-density lipoprotein cholesterol (LDL-C) levels at middle-age constitute a strong risk factor for later cardiovascular events. In older populations, however, LDL-C levels are no longer predictive of cardiovascular mortality or may even seem protective. Whether the altered risk pattern of LDL-C in old age reflects a causal mechanism or is due to confounding and bias is subject to debate. In this review, we briefly discuss the possible explanations for the altered risk pattern of LDL-C observed in old age.Recent findingsUsing examples from the recent literature we illustrate how LDL-C levels 'lose' their predictive value as a cardiovascular risk factor in old age. We review three potential explanations for the changed cardiovascular risk pattern of LDL-C in older populations: survivorship bias, reverse causation, and effect modification.SummaryThe absent or protective effect of LDL-C on cardiovascular mortality in older populations found in observational studies might be explained by survivorship bias, reverse causation, and effect modification. However, this does not necessarily preclude the possibility that (specific) cholesterol-lowering treatment could decrease the risk of morbidity and mortality. Placebo-controlled trials may importantly add to our understanding of who may benefit from lipid-lowering therapy or statins at an older age. copy

Background: Multimorbidity is associated with increased mortality. Certain combinations of diseases are known to be more lethal than others, but the limited knowledge of how the chronology in which diseases develop impacts mortality may impair the development of effective clinical interventions for patients with multimorbidity. Objective: To explore if in multimorbidity the chronology of disease onset is associated with mortality. Design: A prospective nationwide cohort study, including 3,986,209 people aged ≥18 years on 1 January 2000, was performed. We included ten diagnosis groups: lung, musculoskeletal, endocrine, mental, cancer, neurological, gastrointestinal, cardiovascular, kidney, and sensory organs. We defined multimorbidity as the presence of at least two diagnoses from two diagnosis groups (out of ten). To determine mortality, logistic regression models were used to calculate odds ratios (OR) and ratio of ORs (RORs). Results: For most combinations of multimorbidity, the chronology of disease onset does not change mortality. However, when multimorbidity included mental health diagnoses, mortality was in general higher if the mental health diagnosis appeared first. If multimorbidity included heart and sensory diagnoses, mortality was higher if these developed second. For the majority of multimorbidity combinations, there was excess mortality if multimorbidity was diagnosed simultaneously, rather than consecutively, for example, heart and kidney (3.58 ROR; CI 2.39–5.36), or mental health and musculoskeletal diagnoses (2.38 ROR; CI 1.70–3.32). Conclusions: Overall, in multimorbidity, the chronology in which diseases develop is not associated with mortality, with few exceptions. For almost all combinations of multimorbidity, diagnoses act synergistically in relation to mortality if diagnosed simultaneously.

BACKGROUND: The effectiveness of psychotropic medication on behavioral and psychological symptoms of dementia (BPSD) is limited, while associated with a higher risk of adverse events. Non-pharmacological treatment of BPSD is advocated as treatment of first choice. However, many general practitioners (GPs) find it difficult to initiate deprescribing, and when attempting to discontinue psychotropic medication in nursing home residents, they face many barriers. Therefore, we hypothesize that an intervention aimed at improving communication with and involvement of nursing home staff, relatives, and patients by GPs can optimize the pharmacological treatment of BPSD. The aim is to reduce the use of antidepressants in nursing home residents with dementia without increasing morbidity or mortality.OBJECTIVE: The primary outcome is reduction of antidepressant. Secondary outcomes include difference in use of other psychotropic medication, mortality, morbidity, and severity of BPSD.METHOD: The study is a cluster-randomized controlled trial based in general practices in Denmark. We aim to include 22 practices, each of which will recruit up to 15 patients with dementia living in nursing homes. The intervention period is 3 months, and the total study period is 1 year. Randomization is 1:1 to intervention and control group by computer algorithm. Both groups receive education on BPSD and its evidence-based treatment. The intervention includes three tailored components; (1) teaching material and training to be used by the GP to educate nursing home staff on BPSD, (2) a pre-visit reflection tool to encourage nursing home staff to evaluate symptoms and reflect on relatives involvement in the discontinuation process; and (3) a dialog tool to facilitate shared decision making on optimization of BPSD treatment during the visits at the nursing home. The control group includes enhanced care as usual. The primary and secondary outcomes will be assessed at the end of the stud

BACKGROUND: The underlying disease mechanisms of Parkinson's disease (PD) are still unknown and knowledge about risk and prognostic factors is sparse.OBJECTIVE: To examine the association between intelligence, education, body height, and body mass index (BMI) in young adulthood and risk of PD and subsequent survival.METHODS: In total, 656,751 men born 1939-1959 with information from conscription examinations around age 19 years were followed for PD and mortality from 1977-2018 in Danish registries. Cox proportional hazard regression was used to conduct the analyses.RESULTS: During follow-up, 5,264 (0.8%) men were diagnosed with PD. Higher intelligence, education, and body height conferred a higher hazard of PD, independent of age at disease onset. BMI above compared to below the mean (22.8 kg/m2) was associated with slightly higher hazard of late-onset PD (>60 years). During follow-up, 2,125 (40.5%) men with PD died, corresponding to a 2.55 (95% confidence interval:2.44-2.66) times higher mortality compared to men without PD. Intelligence was inversely associated with mortality in men with and without PD. Higher education and body height were also inversely associated with mortality in men without PD, whereas the estimates were less pronounced and imprecisely estimated for men with PD. Having an obese BMI was associated with higher mortality in men with PD.CONCLUSION: Intelligence, education, and body height in young adulthood are positively associated with risk of PD later in life among men. BMI above the mean only confer a higher risk for late-onset PD. For men diagnosed with PD, high intelligence is the only early life indicator associated with better survival, whereas obese BMI predicts poorer survival.

Background: Research on health effects of shift work has especially focused on somatic diseases, such as breast cancer and cardiometabolic disease, while less attention has been given to the association between shift work and mental health.Methods: We used information on 19 964 female nurses (>= 44 years) from the Danish Nurse Cohort, who reported current work schedule (day, evening, night, or rotating) at recruitment (1993/1999). In 5102 nurses who participated in both cohort waves, we defined persistent night shift work as working night shift in 1993 and 1999. We used Cox regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for relevant confounders. Through linkage of cohort participants to national registers, we defined incidence of mood and neurotic disorders as first hospital contact or redeemed prescription until November 2018.Results: We found association between night shift work with mood disorders (HR = 1.31; 95%CI = 1.17 & ndash;1.47) and neurotic disorders (1.29; 1.17 & ndash;1.42), compared to day work. Associations were enhanced in nurses with persistent night shift work (1.85; 1.43 & ndash;2.39 and 1.62; 1.26 & ndash;2.09 for mood and neurotic disorders, respectively) and in nurses with specialist confirmed mood (1.69; 1.24 & ndash;2.29) and neurotic (1.72; 1.22 & ndash;2.44) disorders. Nurses with preexisting psychiatric disorders and full-time work seemed most susceptible.Conclusions: Night shift work is associated with increased risk of major psychiatric disorders. The novel suggestive findings of vulnerable groups, including nurses with a history of psychiatric disorders and full-time workers, are based on a limited number of cases, and further research is needed to confirm the results.

Objective We explored the comparability of anxiety measures from register- and survey-based data including analyses of prevalence and associations with selected psychiatric and somatic diseases. Methods We measured anxiety using Danish registers (hospital diagnosis and anxiolytic drug prescriptions), self-reports, symptom checklist (SCL) scores, and a clinical interview in 7493 adults with mean age 52 (SD 13.3) years who participated in a health survey between 2012 and 2015. We estimated the prevalence of anxiety, agreement between different measures and performed quantitative bias analysis. Results The lifetime prevalence of hospital diagnosed anxiety, anxiolytic drug prescriptions, and self-reported anxiety were 4.4%, 6.2%, and 5.1%, respectively, after adjusting for selective participation. The agreement between the different anxiety measures was low. Thus, 25% with an anxiety diagnosis and 20% with anxiolytic drug prescriptions also had a high SCL score. Anxiolytic drugs were the only measure significantly associated with higher odds of heart disease. Hospital diagnosis and self-reported anxiety were associated with depression with odds ratio (OR) above 15, whereas anxiolytic drug prescriptions were less strongly associated (OR = 2.2(95% confidence interval: 1.26–3.91)). The risk estimates attenuated considerably when correcting for measurement error, whereas the ORs became slightly higher when the selective participation in the survey was accounted for. Conclusion Anxiety diagnosed in hospitals and self-reported anxiety showed low level of agreement but provide comparable results regarding frequency measures and associations with disease outcomes.

INTRODUCTION: This study describes the types and health consequences of medication errors in residential facilities for which the Danish Poison Information Center (DPIC) was contacted.METHODS: This study is based on all inquiries made by residential facilities to the DPIC during a 13-month period. Information about inquirers and residents, data related to the medication error, symptoms, risk assessments and recommendations was collected, and a follow-up phone call was made to evaluate the clinical outcomes, preferably within one week.RESULTS: During the study period, the DPIC received 146 inquiries concerning medication errors in residential facilities. Nearly all inquiries concerned excess administration of medication (96%) and often involved medications targeting the nervous system (65%). In 9% of cases, the DPIC recommended hospitalisation. Most medication errors (92%) were considered of & ldquo;no or minor risk & rdquo;. Administration of medication to the wrong resident is a frequent reason for consulting the DPIC (45%) in cases with medication errors.CONCLUSIONS: In this study, we inventoried the inquiries made to the DPIC about medication errors in residential facilities in Denmark. Most medication errors did not carry a risk of serious health consequences, but continued monitoring is warranted to minimise risk in this vulnerable population. FUNDING: Copenhagen Center for Health Technology (5001105002), Department of Clinical Pharmacology (Bispebjerg Hospital, The Capital Region) (1152871001).TRIAL REGISTRATION: not relevant.

Age-related diseases, including age-related macular degeneration (AMD), are of growing importance in a world where population ageing has become a dominant global trend. Although a wide variety of risk factors for AMD have been identified, age itself remains by far the most important risk factor, making it an urgent priority to understand the connections between underlying ageing mechanisms and pathophysiology of AMD. Ageing is both multicausal and variable, so that differences between individuals in biological ageing processes are the focus of a growing number of pathophysiological studies seeking to explain how ageing contributes to chronic, age-related conditions. The aim of this review is to integrate the available knowledge on the pathophysiology of AMD within the framework of the biology of ageing. One highly significant feature of biological ageing is systemic inflammation, which arises as a second-level response to a first level of molecular damage involving oxidative stress, mutations etc. Combining these insights, the various co-existing pathophysiological explanations in AMD arrange themselves according to a two-level hypothesis. Accordingly, we describe how AMD can be considered the consequence of age-related random accumulation of molecular damage at the ocular level and the subsequent systemic inflammatory host response thereof. We summarize evidence and provide original data to enlighten where evidence is lacking. Finally, we discuss how this two-level hypothesis provides a foundation for thoughts and future studies in prevention, prognosis, and intervention.

Background: The effects of electroconvulsive therapy are usually estimated from changes in depression scales from studies with relatively small patient samples. Larger patient samples can be achieved from epidemiological registers, which provide information on other social and clinical predictors, results and risks. Aims: To examine whether depression severity predicts the use of electroconvulsive therapy, risk of re-hospitalization, suicidal behaviour and mortality following electroconvulsive therapy in patients with major depression. Methods: A cohort of 92,895 patients diagnosed with single or recurrent depression between 2005 and 2016 in the Danish National Patient Registry was followed for electroconvulsive therapy and adverse outcomes. Associations between electroconvulsive therapy and outcomes were analysed using Cox regression. Results: A total of 5004 (5.4%) patients were treated with electroconvulsive therapy. Depression severity was the strongest predictor of electroconvulsive therapy. Electroconvulsive therapy was used more frequently above age 70, in those better educated or married, whereas comorbid alcohol abuse or history of prior stroke at study entry were associated with lower rates. Electroconvulsive therapy was associated with lower mortality. The adjusted hazard ratio for the association between electroconvulsive therapy and suicide in patients with mild depression was 6.99 (3.30–14.43), whereas it was 1.10 (0.55–2.20) in those with severe depression and psychotic symptoms. A similar pattern was seen for emergency contacts and attempted suicide. Conclusions: Electroconvulsive therapy was associated with lower all-cause mortality and the relative risk for re-hospitalization and attempted and committed suicide was lowest in patients with the most severe depression. Electroconvulsive therapy is an important treatment, with significant public health benefits, for patients with severe depression.

BACKGROUND: Numerous risk prediction models use indicators of health to predict mortality in old age. The added value to mortality predictions based on demographic variables is unknown.OBJECTIVE: To evaluate the accuracy of health indicators in predicting all-cause mortality among individuals aged 50+ using area under receiver operating characteristic curve (AUC). Specifically, to assess the added value of health indicators relative to demographic variables.METHODS: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. There were no restrictions on study designs, follow-up duration, language, or publication dates. We also examined the quality of studies using the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies.RESULTS: Out of 804 studies investigating all-cause mortality in older persons, 16 studies were eligible. In community-dwelling populations, the accuracy of demographic variables and health indicators combined ranged from AUC 0.71 to 0.82, indicating modest ability to predict mortality. Age contributed the most to mortality prediction (AUC 0.65 to 0.78) and compared to age and sex, the added values of genetics, physiology, functioning, mood, cognition, nutritional status, subjective health, disease, frailty, and lifestyle ranged from AUC 0.01 to 0.10. The lack of validation samples made it difficult to assess their true added value. Findings were similar in institutionalized populations. Heterogeneity of the studies prevented us from performing a meta-analysis.CONCLUSION: Age and sex contributed the most to mortality predictions in old age while the added value of health indicators is likely to be limited.