Prescription patterns in unipolar depression: A nationwide Danish register-based study of 113,175 individuals followed for 10 years.

BACKGROUND: Evidence-based use of antidepressant medications is of major clinical importance. We aimed to uncover precription patterns in a large cohort of patients with unipolar depression. MATERIAL AND METHODS: Using Danish nationwide registers, we identified individuals with a first-time hospital diagnosis of unipolar depression between January 1st, 2001, and December 31st, 2016. Redemeed prescriptions of antidepressants from five years before to five years after diagnosis were retreived. Lithium and relevant antipsychotics were included. Data were analyzed with descriptive statistics including sunburst plots. Cox regressions were used to rank the risk of treatment failure according to antidepressant category and depression severity, as measured by hazard ratios of drug shift. RESULTS: The full study population consisted of 113,175 individuals. Selective Serotonin Reuptake Inhibitors was the predominantly prescribed first-line group, both before (55.4%) and after (47.7%) diagnosis and across depression severities. Changes of treatment strategy were frequent; 60.8%, 33.7%, and 17.1% reached a second, third, and fourth treatment trial after the hospital diagnosis, respectively. More than half of patients continued their pre-diagnosis antidepressant after diagnosis. The risk of change of treatment strategy was generally lower in mild-moderate depression and higher in severe depression, with tricyclic antidepressants carrying the highest risk in the former and the lowest risks in the latter. Overall, prescribing were often not in accordance with guidelines. CONCLUSION: These findings uncover a potential for improving the clinical care for patients with unipolar depression through optimization of the use of marketed antidepressants.

Adult offspring's education and parental mortality: A nationwide cohort study of the mediating role of lifestyle-related diseases.

Aim: The mechanisms behind the association between adult offspring's socioeconomic position and their parents' mortality are not well understood. This study investigates lifestyle-related diseases as a potential mediating pathway between adult offspring's education and parental mortality. Methods: This nationwide register-based cohort study consists of 963,742 older adults aged 65 years between 2000 and 2018. Lifestyle-related diseases were measured between 60 and 65 years and those with prior lifestyle-related diseases were excluded. Natural Effect Models were performed to assess potential mediation through lifestyle-related diseases of the association between offspring's education and parental mortality measured by additive hazard estimates with 95% confidence intervals (CIs). Results: Between 60 and 65 years, 150,501 (15.6%) older adults were diagnosed with lifestyle-related diseases and 149,647 (15.5%) died during follow-up. Compared with having offspring with long education, short education was associated with 631 (95% CI: 555; 707) and 581 (95% CI: 525; 638) additional deaths per 100,000 person-years for women and men, respectively, of which 15.4% (95% CI: 9.0; 21.6) and 16.8% (95% CI: 14.6; 18.9) were mediated by lifestyle-related diseases. The corresponding numbers for medium education were 276 (95% CI: 205; 347) and 299 (95% CI: 255; 343) with 26.2% (95% CI: 12.0; 40.6) and 27.6% (95% CI: 25.1; 31.8) mediated by lifestyle-related diseases. Conclusions: Lifestyle-related diseases accounted for 15-28% of the association between offspring's education and parental mortality for both men and women.

Psychosocial outcomes and health service use after notifying women participating in population breast screening when they have dense breasts: a BreastScreen Queensland randomised controlled trial.

BACKGROUND: Robust evidence regarding the benefits and harms of notifying Australian women when routine breast screening identifies that they have dense breasts is needed for informing future mammography population screening practice and policy. OBJECTIVES: To assess the psychosocial and health services use effects of notifying women participating in population-based breast cancer screening that they have dense breasts; to examine whether the mode of communicating this information about its implications (print, online formats) influences these effects. METHODS AND ANALYSIS: The study population comprises women aged 40 years or older who attend BreastScreen Queensland Sunshine Coast services for mammographic screening and are found to have dense breasts (BI-RADS density C or D). The randomised controlled trial includes three arms (952 women each): standard BreastScreen care (no notification of breast density; control arm); notification of dense breasts in screening results letter and print health literacy-sensitive information (intervention arm 1) or a link or QR code to online video-based health literacy-sensitive information (intervention arm 2). Baseline demographic data will be obtained from BreastScreen Queensland. Outcomes data will be collected in questionnaires at baseline and eight weeks, twelve months, and 27 months after breast screening. Primary outcomes will be psychological outcomes and health service use; secondary outcomes will be supplemental screening outcomes, cancer worry, perceived breast cancer risk, knowledge about breast density, future mammographic screening intentions, and acceptability of notification about dense breasts. ETHICS APPROVAL: Gold Coast Hospital and Health Service Ethics Committee (HREC/2023/QGC/89770); Sunshine Coast Hospital and Health Service Research Governance and Development (SSA/2023/QSC/89770). DISSEMINATION OF FINDINGS: Findings will be reported in peer-reviewed journals and at national and international conferences. They will also be reported to BreastScreen Queensland, BreastScreen Australia, Cancer Australia, and other bodies involved in cancer care and screening, including patient and support organisations. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12623000001695p (prospective: 9 January 2023).

Sedative drug prescription patterns in Danish adults from 2002 through 2021. A register-based cohort study.

OBJECTIVE: Pharmacological treatment strategies for insomnia seem to vary, and there is lack of knowledge about how sedative drugs are used in a real-world setting. We investigated changes in sedative drug prescription patterns in Danish adults who initiated treatment between 2002 and 2016. METHODS: All adults with a first-time purchase of a sedative drug registered in the Danish National Prescription Register from 2002 through 2016 were followed for five years between 2002 and 2021 for subsequent prescriptions of sedative drugs, death, or emigration. Sedative drugs were classified into anxiolytic benzodiazepines (N05BA), hypnotic benzodiazepines (N05CD), Z-drugs (N05CF), melatonin (N05CH01), promethazine (R06AD), and low-dose quetiapine (N05AH04). Analyses were stratified on time: 2002-2006, 2007-2011, and 2012-2016. RESULTS: A total of 842,880 individuals purchased their first sedative drug between 2002 and 2016. Most of them (40.0%) initiated treatment between 2002 and 2006, whereas 29.2% initiated treatment in 2012-2016. In 2002-2006, anxiolytic benzodiazepines (46.4%), Z-drugs (42.8%), and hypnotic benzodiazepines (5.4%) were the most common first treatment. This pattern changed over time with a gradual increase in the use of melatonin, promethazine, and low-dose quetiapine, which in 2011-2016 accounted for 27% of all first treatments. During the five years from first prescription, around 27% shifted to a different sedative drug. This percentage increased slightly over time, but over time the first shift to another drug class was most often to a Z-drug or anxiolytic benzodiazepine. Few individuals (5.8%) had more than one shift and the third choice seemed randomly distributed across all other drug classes. CONCLUSION: Sedative drug prescriptions are distributed on different drug classes, with Z-drugs and anxiolytic benzodiazepines as the most frequent first treatment, and second choice in case of shift.

Absorbent incontinence pad use and the association with urinary tract infection and frailty: A retrospective cohort study.

Background: Up to 40% of adults over 65 years are full-time users of absorbent incontinence pads due to urinary incontinence. Simultaneously, urinary tract infection is amongst the most common hospital-acquired infection in older patients. Objectives: To explore the association between (1) full-time use of absorbent incontinence pads and urinary tract infection at acute hospital admission, (2) state of frailty and becoming a pad user during hospitalization, and (3) becoming a pad user and acquiring a urinary tract infection during hospitalization in older patients. Design: A retrospective cohort study. Setting: Admissions in an emergency department with transfers to geriatric, cardiac, infectious, or endocrinological wards from September 7th, 2017 to February 18th, 2019. Patients: 1,958 patients aged 65 years or more, having daily homecare or moderate comorbidity, hospitalized due to acute illness, and living in the municipality of Aarhus. Methods: The study was conducted by two researchers reviewing the patients' electronic health records combined with data on frailty status from a geriatric quality database. In the electronic health records, data on baseline characteristics, absorbent incontinence pad use at admission and during the hospital stay, and urinary tract infection were obtained. Results: Full-time users of absorbent incontinence pads had a higher probability of being admitted with urinary tract infection (Odds Ratio=2.00 (95% Confidence Interval: 1.61-2.49); p<.001). Patients identified as severely frail had a higher probability of becoming pad users during hospitalization (Odds Ratio=1.57 (95% Confidence Interval: 1.45-1.71); p<.001) compared to non/mild/moderate frail patients. Patients who became pad users during hospitalization had a higher risk of a hospital-acquired urinary tract infection (Odds Ratio=4.28 (95% Confidence Interval: 1.92-9.52); p<.001). Conclusions: There was an association between the use of absorbent incontinence pads and the development of urinary tract infections in older hospitalized patients, both in full-time users and those who were frail and became pad users during hospitalization. These findings emphasize the need for further research on preventing urinary tract infections and unnecessary pad use in older patients.

The Association of Children and Their Educational Attainment With Diabetes-related Complications and Mortality Among Older Adults With Type 2 Diabetes: A Nationwide Cohort Study.

OBJECTIVE: Socioeconomic resources and family support have been shown to improve adherence to treatment in people with type 2 diabetes (T2D) and are associated with a lower risk of diabetes-related complications and death. We investigated the associations of having children and their educational level with diabetes-related complications and death among older adults with T2D. METHODS: We included 74,588 adults who were at least 65 years of age at the time of T2D diagnosis over the period from 2000 to 2018 in Denmark and grouped them based on having children (yes [reference]/no), and their children's highest educational level (low/medium/high [reference]). Multistate models were performed with 3 states: T2D diagnosis, diabetes-related complications, and death. All models were stratified by other chronic diseases at baseline (yes/no). RESULTS: During follow-up (mean, 5.5 years), 14.6% of the adults developed a complication and 24.8% died with or without complications. Not having children was associated with a higher hazard of death without complications among adults without (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.17 to 1.33) and with (HR, 1.10; 95% CI, 1.02 to 1.18) other chronic diseases and after complications among adults without other chronic diseases (HR, 1.25; 95% CI, 1.12 to 1.38). Having children with a lower educational level was associated with a higher hazard of complications (HRlow, 1.14; 95% CI, 1.05 to 1.24; HRmedium, 1.11; 95% CI, 1.05 to 1.17), death without complications (HRlow, 1.26; 95% CI, 1.17 to 1.36; HRmedium, 1.07; 95% CI, 1.02 to 1.14), and after complications (HRlow, 1.22; 95% CI, 1.07 to 1.39) among adults without other chronic diseases. CONCLUSIONS: Among adults without other chronic diseases, having no children or having children with lower educational levels was associated with a higher hazard of death. Among these adults, having children with lower educational levels was also associated with a higher hazard of diabetes-related complications.

Impact of offspring and their educational level on readmission and death among older adults with chronic obstructive pulmonary disease: a nationwide cohort study using multistate survival models.

BACKGROUND: It is well described that there is social inequality in the disease course of chronic obstructive pulmonary disease (COPD), but the impact of social relations is less explored. We aimed to investigate the impact of adult offspring and their educational level on readmission and death among older adults with COPD. METHODS: In total, 71 084 older adults born 1935-53 with COPD diagnosed at age ≥65 years in 2000-2018 were included. Multistate survival models were performed to estimate the impact of adult offspring (offspring (reference) vs no offspring) and their educational level (low, medium or high (reference)) on the transition intensities between three states: COPD diagnosis, readmission and all-cause death. RESULTS: During follow-up, 29 828 (42.0%) had a readmission and 18 504 (26.0%) died with or without readmission. Not having offspring was associated with higher hazards of death without readmission (HRwomen: 1.52 (95% CI: 1.39 to 1.67), HRmen: 1.29 (95% CI: 1.20 to 1.39)) and a higher hazard of death after readmission for women only (HRwomen: 1.19 (95% CI: 1.08 to 1.30). Having offspring with low educational level was associated with higher hazards of readmission (HRwomen: 1.12 (95% CI: 1.06 to 1.19)), (HRmen: 1.06 (95%CI: 1.002 to 1.12)), death without readmission (HRwomen: 1.24 (95% CI: 1.11 to 1.39)), HRmen: 1.16 (95% CI: 1.05 to 1.29) and death after readmission for men only (HRmen: 1.15 (95% CI: 1.05 to 1.25)). Having offspring with medium educational level was associated with a higher hazard of death without readmission for women (HRwomen: 1.11 (95% CI: 1.02 to 1.21)). CONCLUSION: Adult offspring and their educational level were associated with higher risk of readmission and death among older adults with COPD.

Depression in adulthood and risk of dementia later in life: A Danish register-based cohort study of 595,828 men.

BACKGROUND: Associations between depression and dementia could express a causal relationship, reverse causality or be explained by health-related factors. This study explores the association of depression and indicators of depression severity with subsequent risk of dementia while ensuring temporality and adjusting for important health-related factors. METHOD: 595,828 men from the Danish Conscription Database born in 1939-59 with register-based information on lifetime depression and covariates at age 55 years were followed in nationwide registers to identify dementia cases until 2016. Associations were analyzed using Cox proportional hazard regression models with adjustment for intelligence, education level, body mass index, and comorbidities. RESULTS: The dementia incidence per 1000 person-years was 1.2 cases for men without prior depression and 2.1 and 3.6 cases for men who had depression identified by antidepressants and hospitalization, respectively. Compared to no prior depression, depression identified by antidepressant medication was associated with 1.94 times [95% confidence interval (CI) 1.81;2.07] higher hazard of dementia and depression identified by hospitalization with depression was associated with 2.18 [95% CI: 1.95;2.45] higher hazard of dementia. Long-term course of depression identified by antidepressant prescriptions (>20 prescriptions), was associated with 40% 95% CI: 1.23;1.59 higher hazard of dementia compared to having ≤10 prescriptions. LIMITATIONS: This study is restricted to men and dementia cases until age 57-77 years. CONCLUSION: Men with depression before late midlife are subject to a higher risk of dementia later in life. Clinicians should be aware of dementia symptoms in patients with a long history of depression to initiate early treatment.

Establishment and Characterization of Paired Primary Cultures of Human Pancreatic Cancer Cells and Stellate Cells Derived from the Same Tumor.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely poor prognosis, and its treatment remains a challenge. As the existing in vitro experimental models offer only a limited resemblance to human PDAC, there is a strong need for additional research tools to better understand PDAC tumor biology, particularly the impact of the tumor stroma. Here, we report for the first time the establishment and characterization of human PDAC-derived paired primary monolayer cultures of (epithelial) cancer cells (PCCs) and mesenchymal stellate cells (PSCs) derived from the same tumor by the outgrowth method. Characterization of cell morphology, cytostructural, and functional profiles and proteomics-based secretome analysis were performed. All PCCs harbored KRAS and TP53 mutations, and expressed cytokeratin 19, ki-67, and p53, while the expression of EpCAM and vimentin was variable. All PSCs expressed α-smooth muscle actin (α-SMA) and vimentin. PCCs showed a significantly higher growth rate and proliferation than PSCs. Secretome analysis confirmed the distinct nature of PCCs as compared to PSCs and allowed identification of potential molecular regulators of PSC-conditioned medium (PSC-CM)-induced migration of PCCs. Paired primary cultures of PCCs and PSCs derived from the same tumor specimen represent a novel experimental model for basic research in PDAC tumor biology.

Physical activity promotion in primary care: bridging the gap between research and practice.

BACKGROUND: While a growing literature supports the effectiveness of physical activity interventions delivered in the primary care setting, few studies have evaluated efforts to increase physician counseling on physical activity during routine practice (i.e., outside the context of controlled research). This paper reports the results of a dissemination trial of a primary care-based physical activity counseling intervention conducted within the context of a larger, multi-strategy, Australian community-based, physical activity intervention, the 10,000 Steps Rockhampton Project. METHODS: All 23 general practices and 66 general practitioners (GPs, the Australian equivalent of family physicians) were invited to participate. Practice visits were made to consenting practices during which instruction in brief physical activity counseling was offered, along with physical activity promotion resources (print materials and pedometers). The evaluation, guided by the RE-AIM framework, included collection of process data, as well as pre- and post-intervention data from a mailed GP survey, and data from the larger project's random-digit-dialed, community-based, cross-sectional telephone survey that was conducted in Rockhampton and a comparison community. RESULTS: Ninety-one percent of practices were visited by 10,000 Steps staff and agreed to participate, with 58% of GPs present during the visits. General practitioner survey response rates were 67% (n =44/66 at baseline) and 71% (n =37/52, at 14-month follow-up). At follow-up, 62% had displayed the poster, 81% were using the brochures, and 70% had loaned pedometers to patients, although the number loaned was relatively small. No change was seen in GP self-report of the percentage of patients counseled on physical activity. However, data from the telephone surveys showed a 31% increase in the likelihood of recalling GP advice on physical activity in Rockhampton (95% confidence interval [CI]=1.11-1.54) compared to a 16% decrease (95% CI=0.68-1.04) in the comparison community. CONCLUSIONS: This dissemination study achieved high rates of GP uptake, reasonable levels of implementation, and a significant increase in the number of community residents counseled on physical activity. These results suggest that evidence-based primary care physical activity counseling protocols can be translated into routine practice, although the initial and ongoing investment of time to develop partnerships with relevant healthcare organizations, and the interest generated by the overall 10,000 Steps program should not be underestimated.