Developing a prediction model to identify people with severe mental illness without regular contact to their GP - a study based on data from the Danish national registers.

INTRODUCTION: People with severe mental illness (SMI) face a higher risk of premature mortality due to physical morbidity compared to the general population. Establishing regular contact with a general practitioner (GP) can mitigate this risk, yet barriers to healthcare access persist. Population initiatives to overcome these barriers require efficient identification of those persons in need. OBJECTIVE: To develop a predictive model to identify persons with SMI not attending a GP regularly. METHOD: For individuals with psychotic disorder, bipolar disorder, or severe depression between 2011 and 2016 (n = 48,804), GP contacts from 2016 to 2018 were retrieved. Two logistic regression models using demographic and clinical data from Danish national registers predicted severe mental illness without GP contact. Model 1 retained significant main effect variables, while Model 2 included significant bivariate interactions. Goodness-of-fit and discriminating ability were evaluated using Hosmer-Lemeshow (HL) test and area under the receiver operating characteristic curve (AUC), respectively, via cross-validation. RESULTS: The simple model retained 11 main effects, while the expanded model included 13 main effects and 10 bivariate interactions after backward elimination. HL tests were non-significant for both models (p = 0.50 for the simple model and p = 0.68 for the extended model). Their respective AUC values were 0.789 and 0.790. CONCLUSION: Leveraging Danish national register data, we developed two predictive models to identify SMI individuals without GP contact. The extended model had slightly better model performance than the simple model. Our study may help to identify persons with SMI not engaging with primary care which could enhance health and treatment outcomes in this group.

The development of type 2 diabetes management in people with severe mental illness in the Capital Region of Denmark 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 identified as having T2D. In 2015, 1.5% of the study population had schizophrenia spectrum disorder and 1.4% had an affective disorder. The number of people who used biochemical tests or had poor biochemical risk factor control was essentially unrelated to SMI status. One exception was that fewer LDL cholesterol tests were done on people with affective disorders and schizophrenia spectrum disorders at the beginning of the study period compared to people in the non-SMI group. This difference gradually diminished and was almost nonexistent by 2011. There was also a slightly slower rise in UACR test rates in the SMI groups compared to other people with T2D during the period. Throughout the study period, all groups changed their use of medications in similar ways: more metformin, less sulfonylurea, more lipid-lowering drugs, and more ACEi/ARBs. However, people with schizophrenia disorder consistently used fewer cardiovascular medications. Cardiovascular events were more common in the affective disorder group compared to the non-SMI group from 2009 to 2015 (rate ratio 2015 : 1.36 [95% CI 1.18-1.57]). After adjustment for age and sex, all-cause mortality was significantly higher among people with a schizophrenia spectrum disorder each year from 2003 to 2015 compared to the non-SMI group (rate ratio 2015 : 1.99 [95% CI 1.26-3.12]). CONCLUSION: Persons with schizophrenia or affective disorders demonstrated the same treatment changes for T2D as those without SMI in general practice. The lower use of most types of cardiovascular medications among people with schizophrenia disorders indicates potential undertreatment of hypertension and dyslipidemia and remains throughout the study period. Cardiovascular events were most common among people with affective disorders, but this was not reflected in a higher proportion using cardiovascular preventive medications. This knowledge should be considered in the management of this vulnerable patient group.

Use of hypnotic-sedative medication and risk of falls and fractures in adults: A self-controlled case series study.

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.

Diabetes treatment for persons with severe mental illness: A registry-based cohort study to explore medication treatment differences for persons with type 2 diabetes with and without severe mental illness.

It has been argued that persons with severe mental illness (SMI) receive poorer treatment for somatic comorbidities. This study assesses the treatment rates of glucose-lowering and cardiovascular medications among persons with incident type 2 diabetes (T2D) and SMI compared to persons with T2D without SMI. We identified persons ≥30 years old with incident diabetes (HbA1c ≥ 48 mmol/mol and/or glucose ≥ 11.0 mmol/L) from 2001 through 2015 in the Copenhagen Primary Care Laboratory (CopLab) Database. The SMI group included persons with psychotic, affective, or personality disorders within five years preceding the T2D diagnosis. Using a Poisson regression model, we calculated the adjusted rate ratios (aRR) for the redemption of various glucose-lowering and cardiovascular medications up to ten years after T2D diagnosis. We identified 1,316 persons with T2D and SMI and 41,538 persons with T2D but no SMI. Despite similar glycemic control at diagnosis, persons with SMI redeemed a glucose-lowering medication more often than persons without SMI in the period 0.5-2 years after the T2D diagnosis; for example, the aRR was 1.05 (95% CI 1.00-1.11) in the period 1.5-2 years after the T2D diagnosis. This difference was mainly driven by metformin. In contrast, persons with SMI were less often treated with cardiovascular medications during the first 3 years after T2D diagnosis, e.g., in the period 1.5-2 years after T2D diagnosis, the aRR was 0.96 (95% CI 0.92-0.99). For people with SMI in addition to T2D, metformin is more likely to be used in the initial years after T2D diagnosis, while our results suggest potential room for improvement regarding the use of cardiovascular medications.

Altered cardiovascular risk pattern of LDL cholesterol in older adults.

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.

Tailoring a complex intervention to reduce antidepressants in institutionalized older persons with dementia.

INTRODUCTION: First-line treatment for behavioral and psychiatric symptoms of dementia is non-pharmacological. Still, psychotropic medication is widely used, despite its limited effect and harmful side-effects. More than half of all nursing home residents with dementia receive antidepressants, even though deprescribing is safe and feasible. Interventions to promote deprescribing of antidepressants in nursing homes are few and complex. To optimize the deprescribing process through an intervention, transparency for the development of the intervention is needed. We aim to describe the steps in the development and tailoring of an intervention targeting GPs, nursing home staff, and relatives to enhance collaboration on reducing the use of antidepressants in institutionalized older persons with dementia in Denmark. METHOD: A step-wise process guided by the core elements in the Medical Research Council constituted the tailoring process. Five steps were included; 1) a literature search, 2) interviews with stakeholders, 3) drafting the intervention prototype, 4) professionals' assessment of the intervention, and 5) refinement of the intervention. The steps were conducted from June 2020 to June 2022. RESULTS: Based on the literature search, interviews with stakeholders, and professionals' assessment of the intervention, four main themes were identified; 1) focusing on antidepressants, 2) importance of professional qualifications, 3) collaboration and communication, and 4) patient and relative involvement. They guided intervention development and refinement of the final intervention, which included 1) a case-based training course and 2) a dialog tool including a symptom assessment scale to be used in a structured consultation at the nursing home. CONCLUSION: This study presents a detailed account of the tailoring process for a complex intervention to optimize deprescribing of antidepressants for older persons with dementia at nursing homes. By presenting a thorough development process, we expect to achieve increased adherence to the intervention which is currently being tested in an ongoing cluster randomized controlled trial. The transparency of the process will also increase the future development of other similar complex interventions.

A cluster-randomized trial of a complex intervention to encourage deprescribing antidepressants in nursing home residents with dementia: a study protocol.

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 study period. A process evaluation will be conducted to assess the implementability. DISCUSSION: We anticipate that the intervention will optimize the treatment of BPSD with antidepressants for nursing homes residents and enhance compliance with reduction of medication. The process evaluation should provide insights into the barriers and facilitators to changing the current practice of deprescribing. TRIAL REGISTRATION: Clinicaltrials.gov NCT04985305 . Registered on 30 July 2021.

Associations of Young Adult Intelligence, Education, Height, and Body Mass Index with Subsequent Risk of Parkinson's Disease and Survival: A Danish Cohort Study.

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.

What Makes Deprescription of Psychotropic Drugs in Nursing Home Residents with Dementia so Challenging? A Qualitative Systematic Review of Barriers and Facilitators.

BACKGROUND: Behavioral and psychological symptoms of dementia are frequently experienced in the nursing home setting and place a substantial burden on patients, relatives, and nursing home staff. Despite guidelines recommending non-pharmacological treatments, psychotropic drugs are often prescribed to address these symptoms. This is the case despite their effects being limited, and there being a risk of side effects and adverse events for the patient. Several studies have aimed to reduce the use of psychotropic drugs, with varying results. The reasons behind these variations are not well understood. OBJECTIVES: The objective of this systematic review was to investigate which factors nursing home general practitioners and nursing home staff experience as barriers or facilitators when attempting to deprescribe psychotropic drugs in nursing home residents. METHODS: We searched PubMed, EMBASE, psycINFO, Web of Science, and CINAHL between April and September 2020. An inductive method using thematic analysis of the qualitative findings was applied for the derivation of themes. Quantitative studies were included but described descriptively and separately. RESULTS: Of 8204 unique records, 14 studies were included in the review. Of these, nine were interview or focus group studies and five were survey studies. Thematic analysis resulted in five major themes identified as either facilitators or barriers or both: (1) 'Operationality and routines'; (2) 'Lack of resources and qualifications'; (3) 'Patient-related outcomes', which points to a strong belief in negative patient-related outcomes of discontinuation and a downplay of side effects of the medication; (4) 'Policies', including support and buy-in from nursing home leadership; and (5) 'Collaboration' between physicians and nursing home staff. Themes 1 and 4 consist of facilitators. Theme 2 consists of barriers. Theme 3 and 5 consist of both facilitators and barriers. Evaluation of closed-ended questions from the surveys supported the findings. CONCLUSIONS: Deprescribing psychotropic drugs used for behavioral and psychological symptoms of dementia in nursing home residents is challenging. Resources need to be in place for deprescribing, as well as there being a focus on the positive patient-related outcomes of doing so. Managerial support, staff routines, and interprofessional collaboration are some factors facilitating the process, in addition to there being routines and systematic procedures in place allowing for operationality and a common understanding. Addressing these barriers and facilitators is necessary to ensure that deprescribing can be understood as meaningful and pursued among healthcare professionals in the nursing home setting.

Body mass index and height in young adult men in relation to subsequent risk of mood disorder.

Adolescence represents an important period in brain and mental development, which raises the question of whether measures of body size at entry into adult life influence the risk of developing mood disorders. We examined the association of BMI and height in a cohort of young men with risk of mood disorders throughout life. The study included 630,807 Danish men born 1939-1959 and 1983-1997 with measures of height and weight at conscription board examinations. Psychiatrist's diagnosis of mood disorders was obtained from national patient registries from 1969 to 2016. The associations of BMI and height with mood disorders were estimated by Cox proportional hazard regression analyses adjusting for education, cognitive ability, migration status drug and alcohol misuse. During a mean follow-up of 26.3 years, 2,608 (0.6%) and 19,690 (3.1%) men were diagnosed with bipolar disorder and depression, respectively. We found an inverse linear association of BMI with risk of bipolar disorder, whereas the association of BMI with depression was curve-linear with a decline in risk until BMI around 25 kg/m2, and an almost constant risk across the BMI range above 25 kg/m2. Height was not associated with bipolar disorder or depression. Comparison of brothers, assumed to share family factors of possible influence on the risk of mood disorders, showed similar results although with wider confidence intervals. BMI in the lower range at men's entry into adulthood is inversely associated with risk of bipolar disorder and depression throughout adult life, whereas height is not related.

Use of register- and survey-based measures of anxiety in a population-based Danish cohort.

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.

Shift work and incidence of psychiatric disorders: The Danish Nurse Cohort study.

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 = 1.17-1.47) and neurotic disorders (1.29; 1.17-1.42), compared to day work. Associations were enhanced in nurses with persistent night shift work (1.85; 1.43-2.39 and 1.62; 1.26-2.09 for mood and neurotic disorders, respectively) and in nurses with specialist confirmed mood (1.69; 1.24-2.29) and neurotic (1.72; 1.22-2.44) 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.

Electroconvulsive therapy, depression severity and mortality: Data from the Danish National Patient Registry.

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.

Life Events, Emotions, and Immune Function: Evidence from Whitehall II Cohort Study.

Stressful life events have been shown to increase vulnerability to infections. However, the effects may be dependent on specific emotional responses associated with these events. In general, negative emotions are thought to exacerbate and positive emotions to protect from the adverse effects of stressors on health. In this study, we adopted an evolutionary and functionalist perspective on emotions and hypothesized that both positive and negative emotions in response to stressful events are protective, whereas absence of emotional reactions exacerbates vulnerability to infections. We assessed immune function using lymphocytes to white blood cells ratio as a proxy for current viral infection in 3,008 British civil workers (30% women). No main effect of stressful life events or emotions on lymphocyte ratio was observed in either sex. However, in men, there was an interaction of life events with both positive and negative emotions as well as a combined measure of general affect. Supporting our hypothesis, stressful life events were associated with impaired immune function in men who reported very low levels of both positive and negative emotions but not in others. We discuss potential benefits of negative and positive emotions in the context of stress and immunity.

Electroconvulsive therapy and later stroke in patients with affective disorders.

The long-term effects of electroconvulsive therapy (ECT) on the risk of stroke are unknown. We examined the association between ECT and risk of incident or recurrent stroke. A cohort of 174 534 patients diagnosed with affective disorder between 2005 and 2016 in the Danish National Patient Registry were followed for stroke until November 2016. The association between ECT and stroke was analysed using Cox regression with multiple adjustment and propensity-score matching on sociodemographic and clinical variables. In 162 595 patients without previous stroke, 5781 (3.6%) were treated with ECT. The total number of patients developing stroke during follow-up was 3665, of whom 165 had been treated with ECT. In patients <50 years, ECT was not associated with stroke (adjusted hazard ratio (HR) = 1.29, 95% CI 0.87-1.93). In patients ≥50, ECT was associated with a lower risk of stroke (adjusted HR = 0.69, 95% CI 0.57-0.89), but this estimate was likely influenced by competing mortality risk. Of 11 939 patients with a history of stroke, 228 (1.9%) were treated with ECT. During follow-up, 2330 (19.5%) patients had a recurrence, of which 26 were patients treated with ECT. ECT was not associated with risk of a new event (HR = 0.69, 95% CI 0.46-1.00; P = 0.05). ECT is not associated with an elevated risk of incident or recurrent stroke.Declaration of interestNone.

Hearing loss, cognitive ability, and dementia in men age 19-78 years.

Hearing loss in later life has been associated with risk of dementia. The impact of risk factors for dementia may change during life, and it is unknown whether hearing loss early in midlife represents a risk factor for dementia. We examined whether hearing loss diagnosed in midlife was associated with an increased risk of dementia. A cohort comprising 942,567 Danish men enrolled in the mandatory conscription board examination was followed from conscription (age 19). Cognitive ability was measured at conscription, while hearing loss was ascertained either by physicians diagnosis at conscription or by the Danish National Patient Registry from 1977 to 2016 (ICD-8:388; 389; ICD-10:H90; H91). Differences in cognitive ability in relation to hearing loss at conscription were calculated using t test, while the risk of dementia associated with hearing loss was estimated using Cox regression with adjustment for cognitive ability, education, depression, diabetes, hypertension, and cerebrovascular disease. Men with hearing loss at conscription had about 2 points (corresponding to 0.20 SD) lower mean cognitive score than those without hearing loss. During follow-up, 59,834 men had a hearing loss diagnosis, while 9114 were diagnosed with dementia. Midlife hearing loss was associated with an increased rate of dementia diagnosed before age 60 (adjusted Hazard Ratio (HR) = 1.90 [95% CI 1.59-2.76]) or at a later age (adjusted HR = 1.15 [95% CI 1.06-1.25]). Our study supports the evidence that early identification and correction of hearing loss holds promise for prevention of dementia later in life.

The added value of health indicators to mortality predictions in old age: A systematic review.

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.

Young adult cognitive ability and subsequent major depression in a cohort of 666,804 Danish men.

BACKGROUND: Early life cognitive ability (CA) might influence the risk of developing major depression (MD). The aim was to investigate the association between young adult CA and subsequent MD in relation to different MD disease characteristics. METHODS: Information on CA was assessed at conscription board examinations 1957-1984 (mean age 19 years) and information on MD was based on hospital diagnosis retrieved from Danish Patient registers 1969-2015. Associations between CA and MD were examined using Cox regression analyses. RESULTS: A total of 666,804 men (born 1939-1959) were followed and 25,841 (3.9%) developed MD during a mean follow-up of 40.8 years. Lower CA was associated with an increased risk of incident MD. The association was stronger for early-onset (<60 years) (HRper1SDdecrease = 1.23; 95%CI:1.21,1.24) compared to late-onset (≥60 years) MD (HRper1SDdecrease = 1.14; 95%CI:1.11,1.16), but CA was not related to number of depressive episodes. The association was stronger for single depressive episodes (HRper1SDdecrease = 1.21; 95%CI:1.19,1.23) compared to recurrent depression (HRper1SDdecrease = 1.13; 95%CI:1.09,1.16), while the strength of the association did not differ according to MD disease severity (ICD10: mild, moderate, and severe depression). LIMITATIONS: The study sample only included men and only MD cases diagnosed at hospital were included which limits the generalizability. CONCLUSION: Low CA could be a risk factor for especially early onset MD in men, whereas the influence of CA on re-occurrence seems less strong. Lower pre-morbid CA increases the risk of MD and should therefore be part of the depression risk assessment in clinical practice.

Electroconvulsive therapy and risk of dementia in patients with affective disorders: a cohort study.

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment for severe episodes of mood disorders. Temporary memory loss is a common side-effect, but ongoing discussions exist regarding potential long-term adverse cognitive outcomes. Only a few studies have examined the frequency of dementia in patients after ECT. The aim of this study was to examine the association between ECT and risk of subsequent dementia in patients with a first-time hospital diagnosis of affective disorder. METHODS: We did a cohort study of patients aged 10 years and older in Denmark with a first-time hospital contact for an affective disorder from Jan 1, 2005, through Dec 31, 2015, identified in the Danish National Patient Registry with ICD-10 codes F30.0 to F39.9. From the registry we retrieved information on all ECTs registered for patients and followed up patients for incidental dementia (defined by hospital discharge diagnoses or acetylcholinesterase inhibitor use) until Oct 31, 2016. We examined the association between ECT and dementia using Cox regression analyses with multiple adjustments and propensity-score matching on sociodemographic and clinical variables. FINDINGS: Of 168 015 patients included in the study, 5901 (3·5%) patients had at least one ECT. During the median follow-up of 4·9 years (IQR 2·4-7·8) and 872 874 person years, the number of patients who developed dementia was 111 (0·1%) of 99 045 patients aged 10-49 years, 965 (2·7%) of 35 945 aged 50-69 years, and 4128 (12·5%) of 33 025 aged 70-108 years. 217 (3·6%) of the 5901 patients treated with ECT developed dementia, whereas of 162 114 patients not treated with ECT 4987 (3·1%) developed dementia. The corresponding incidences were 70·4 cases per 10 000 person-years (95% CI 61·6-80·5) and 59·2 per 10 000 person-years (57·6-60·8). In patients younger than 50 years and 50-69 years, ECT was not associated with a risk of dementia compared with age-matched patients who were not given ECT (age-adjusted hazard ratio [HR] 1·51, 95% CI 0·67-3·46, p=0·32; and 1·15, 0·91-1·47, p=0·22, respectively). In patients aged 70 years and older, ECT was associated with a decreased rate of dementia (0·68, 95% CI 0·58-0·80; p<0·0001), but in the propensity-score matched sample the HR was attenuated (0·77, 0·59-1·00; p=0·062). 31 754 patients (17·6%) died during follow-up (mortality rate per 1000 person-years 35·7, 95% CI 35·3-36·2) and supplementary analyses suggested that the risk of dementia, taking the competing mortality risk into account, was not significantly associated with ECT (subdistribution HR 0·98, 95% CI 0·76-1·26; p=0·24). INTERPRETATION: ECT was not associated with risk of incidental dementia in patients with affective disorders after correcting for the potential effect of patient selection or competing mortality. The findings from this study support the continued use of ECT in patients with severe episodes of mood disorders, including those who are elderly. FUNDING: Danish Council for Independent Research, Danish Medical Research Council, the Velux Foundation, the Jascha Foundation, and the Doctor Sofus Carl Emil Friis and Olga Doris Friis grant.

Profit (p)-index: the degree to which authors profit from co-authors.

Current metrics for estimating a scientist's academic performance treat the author's publications as if these were solely attributable to the author. However, this approach ignores the substantive contributions of co-authors, leading to misjudgments about the individual's own scientific merits and consequently to misallocation of funding resources and academic positions. This problem is becoming the more urgent in the biomedical field where the number of collaborations is growing rapidly, making it increasingly harder to support the best scientists. Therefore, here we introduce a simple harmonic weighing algorithm for correcting citations and citation-based metrics such as the h-index for co-authorships. This weighing algorithm can account for both the nvumber of co-authors and the sequence of authors on a paper. We then derive a measure called the 'profit (p)-index', which estimates the contribution of co-authors to the work of a given author. By using samples of researchers from a renowned Dutch University hospital, Spinoza Prize laureates (the most prestigious Dutch science award), and Nobel Prize laureates in Physiology or Medicine, we show that the contribution of co-authors to the work of a particular author is generally substantial (i.e., about 80%) and that researchers' relative rankings change materially when adjusted for the contributions of co-authors. Interestingly, although the top University hospital researchers had the highest h-indices, this appeared to be due to their significantly higher p-indices. Importantly, the ranking completely reversed when using the profit adjusted h-indices, with the Nobel laureates having the highest, the Spinoza Prize laureates having an intermediate, and the top University hospital researchers having the lowest profit adjusted h-indices, respectively, suggesting that exceptional researchers are characterized by a relatively high degree of scientific independency/originality. The concepts and methods introduced here may thus provide a more fair impression of a scientist's autonomous academic performance.