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Bidirectional associations between treatment-resistant depression and general medical conditions
No full textDepression is associated with general medical conditions (GMCs), but it is not known if treatment-resistant depression (TRD) affects GMC risk and vice versa. We estimated bidirectional associations between TRD and GMCs (prior and subsequent). All individuals aged 18–69 years, born and living in Denmark, with a first-time prescription for an antidepressant between 2005 and 2012 were identified in the Danish Prescription Registry (N = 154,513). TRD was defined as at least two shifts in treatment regimes. For prior GMCs, we estimated odds ratios (ORs) using conditional logistic regression comparing TRD patients with matched non-TRD controls adjusted for other GMCs and number of other GMCs. For subsequent GMCs, we used Cox regression to calculate hazard ratios (HRs) in TRD vs. non-TRD patients adjusted for age at first prescription, calendar time, other GMCs and number of other GMCs. Patients with TRD had higher prevalence of prior GMCs related to the immune or neurological systems; musculoskeletal disorders (women aOR: 1.35, 95% CI: 1.26–1.46, men aOR: 1.30, 95% CI: 1.19–1.42) and migraine (women aOR: 1.22, 95% CI: 1.09–1.36, men aOR: 1.25, 95% CI: 1.00–1.56). Subsequent GMCs were related to a broader spectrum; cardiovascular (women aHR: 1.43, 95% CI: 1.32–1.54, men aHR: 1.31, 95% CI: 1.19–1.43), endocrine (women aHR: 1.52, 95% CI: 1.37–1.67, men aHR: 1.24, 95% CI: 1.07–1.44), and neurological disorders (women aHR: 1.24, 95% CI: 1.13–1.35, men aHR: 1.19, 95% CI: 1.07–1.34). Our study presents a broad overview of comorbid medical conditions in patients with TRD and further studies are needed to explore the associations in detail.</p
COVID-19
No full textBackground: The Dutch province of Limburg borders the German district of Heinsberg, which had a large cluster of COVID-19 cases linked to local carnival activities before any cases were reported in the Netherlands. However, Heinsberg was not included as an area reporting local or community transmission per the national case definition at the time. In early March, two residents from a long-term care facility (LTCF) in Sittard, a Dutch town located in close vicinity to the district of Heinsberg, tested positive for COVID-19. In this study we aimed to determine whether cross-border introduction of the virus took place by analysing the LTCF outbreak in Sittard, both epidemiologically and microbiologically. Methods: Surveys and semi-structured oral interviews were conducted with all present LTCF residents by health care workers during regular points of care for information on new or unusual signs and symptoms of disease. Both throat and nasopharyngeal swabs were taken from residents suspect of COVID-19, based on regional criteria, for the detection of SARS-CoV-2 by Real-time Polymerase Chain Reaction. Additionally, whole genome sequencing was performed using a SARS-CoV-2 specific amplicon-based Nanopore sequencing approach. Moreover, twelve random residents were sampled for possible asymptomatic infections. Results: Out of 99 residents, 46 got tested for COVID-19. Out of the 46 tested residents, nineteen (41%) tested positive for COVID-19, including 3 asymptomatic residents. CT-values for asymptomatic residents seemed higher compared to symptomatic residents. Eleven samples were sequenced, along with three random samples from COVID-19 patients hospitalized in the regional hospital at the time of the LTCF outbreak. All samples were linked to COVID-19 cases from the cross-border region of Heinsberg, Germany. Conclusions: Sequencing combined with epidemiological data was able to virtually prove cross-border transmission at the start of the Dutch COVID-19 epidemic. Our results highlight the need for cross-border collaboration and adjustment of national policy to emerging region-specific needs along borders in order to establish coordinated implementation of infection control measures to limit the spread of COVID-19.</p
Combined Longitudinal Clinical and Autopsy Phenomic Assessment in Lethal Metastatic Prostate Cancer
No full textBackground: Systematic identification of data essential for outcome prediction in metastatic prostate cancer (mPC) would accelerate development of precision oncology. Objective: To identify novel phenotypes and features associated with mPC outcome, and to identify biomarker and data requirements to be tested in future precision oncology trials. Design, setting, and participants: We analyzed deep longitudinal clinical, neuroendocrine expression, and autopsy data of 33 men who died from mPC between 1995 and 2004 (PELICAN33), and related findings to mPC biomarkers reported in the literature. Intervention: Thirty-three men prospectively consented to participate in an integrated clinical-molecular rapid autopsy study of mPC. Outcome measurements and statistical analysis: Data exploration with correction for multiple testing and survival analysis from the time of diagnosis to time to death and time to first occurrence of severe pain as outcomes were carried out. The effect of seven complications on the modeled probability of dying within 2 yr after presenting with the complication was evaluated using logistic regression. Results and limitations: Feature exploration revealed novel phenotypes related to mPC outcome. Four complications (pleural effusion, severe anemia, severe or controlled pain, and bone fracture) predict the likelihood of death within 2 yr. Men with Gleason grade group 5 cancers developed severe pain sooner than those with lower-grade tumors. Surprisingly, neuroendocrine (NE) differentiation was frequently observed in the setting of high serum prostate-specific antigen (PSA) levels (≥30 ng/ml). In 4/33 patients, no controlled (requiring analgesics) or severe pain was detected, and strikingly, 14/15 metastatic sites studied in these men did not express NE markers, suggesting an inverse relationship between NE differentiation and pain in mPC. Intracranial subdural metastasis is common (36%) and is usually clinically undetected. Categorization of “skeletal-related events” complications used in recent studies likely obscures the understanding of spinal cord compression and fracture. Early death from prostate cancer was identified in a subgroup of men with a low longitudinal PSA bandwidth. Cachexia is common (body mass index <0.89 in 24/31 patients) but limited to the last year of life. Biomarker review identified 30 categories of mPC biomarkers in need of winnowing in future trials. All findings require validation in larger cohorts, preferably alongside data from this study. Conclusions: The study identified novel outcome subgroups for future validation and provides “vision for mPC precision oncology 2020–2050” draft recommendations for future data collection and biomarker studies. Patient summary: To better understand variation in metastatic prostate cancer behavior, we assembled and analyzed longitudinal clinical and autopsy records in 33 men. We identified novel outcomes, phenotypes, and aspects of disease burden to be tested and refined in future trials.</p
The safety of banks in Vietnam using CAMEL
No full textA key, important, and popular set of criteria to evaluate the safety, stability, and sustainability of banks is the CAMEL method. The CAMEL system is an abbreviation for indicators that consists of a ranking system for a bank, and includes 5 chief ingredients, namely Capital Adequacy, Asset Quality, Management Quality, Earnings, and Liquidity. Banks need to comply with the CAMEL system in order to facilitate the bank to operate sustainably, safely, and grow larger and stronger. The primary interest in the paper is to analyze the safety, stability, and sustainability of banks in Vietnam. Based on financial statements, data are collected from banks in Vietnam from 2014 to 2017, and the CAMEL method is used to investigate the safety, profitability, liquidity, and risk management of these banks. The data were collected and stored according to banking regulations in Vietnam that have changed over time.</p
“Why call it tourist season if we can't shoot them?”–Towards the Utopian sensitized tourist
No full textThis paper argues for increased awareness of local cultures through an educational approach, as it is explored in the CultSense project. The tourist experience is a multi-layered phenomenon moderated by a dynamic relationship with the places visited and local populations. A holistic approach to tourism tensions and challenges, as well as a more pro-active attitude from all stakeholders involved are important in finding strategic solutions. The project proposes an alternative approach, developing bottom-up initiatives that give a voice to local actors and develop global intercultural awareness for (young) travellers. The dissemination of methodological and pedagogical tools by third parties should add to the body of knowledge around sensitized forms of tourism, stimulating non-demeaning and non-patronising attitudes achieved through a grassroots approach.</p
Socioeconomic differences in healthcare expenditure and utilization in The Netherlands
No full textBackground: Worldwide, socioeconomic differences in health and use of healthcare resources have been reported, even in countries providing universal healthcare coverage. However, it is unclear how large these socioeconomic differences are for different types of care and to what extent health status plays a role. Therefore, our aim was to examine to what extent healthcare expenditure and utilization differ according to educational level and income, and whether these differences can be explained by health inequalities. Methods: Data from 18,936 participants aged 25–79 years of the Dutch Health Interview Survey were linked at the individual level to nationwide claims data that included healthcare expenditure covered in 2017. For healthcare utilization, participants reported use of different types of healthcare in the past 12 months. The association of education/income with healthcare expenditure/utilization was studied separately for different types of healthcare such as GP and hospital care. Subsequently, analyses were adjusted for general health, physical limitations, and mental health. Results: For most types of healthcare, participants with lower educational and income levels had higher healthcare expenditure and used more healthcare compared to participants with the highest educational and income levels. Total healthcare expenditure was approximately between 50 and 150 % higher (depending on age group) among people in the lowest educational and income levels. These differences generally disappeared or decreased after including health covariates in the analyses. After adjustment for health, socioeconomic differences in total healthcare expenditure were reduced by 74–91 %. Conclusions: In this study among Dutch adults, lower socioeconomic status was associated with increased healthcare expenditure and utilization. These socioeconomic differences largely disappeared after taking into account health status, which implies that, within the universal Dutch healthcare system, resources are being spent where they are most needed. Improving health among lower socioeconomic groups may contribute to decreasing health inequalities and healthcare spending.</p
A single subcutaneous or intranasal immunization with adenovirus-based SARS-CoV-2 vaccine induces robust humoral and cellular immune responses in mice
No full textOptimal vaccines are needed for sustained suppression of SARS-CoV-2 and other novel coronaviruses. Here, we developed a recombinant type 5 adenovirus vector encoding the gene for the SARS-CoV-2 S1 subunit antigen (Ad5.SARS-CoV-2-S1) for COVID-19 immunization and evaluated its immunogenicity in mice. A single immunization with Ad5.SARS-CoV-2-S1 via S.C. injection or I.N delivery induced robust antibody and cellular immune responses. Vaccination elicited significant S1-specific IgG, IgG1, and IgG2a endpoint titers as early as 2 weeks, and the induced antibodies were long lasting. I.N. and S.C. administration of Ad5.SARS-CoV-2-S1 produced S1-specific GC B cells in cervical and axillary LNs, respectively. Moreover, I.N. and S.C. immunization evoked significantly greater antigen-specific T-cell responses compared to unimmunized control groups with indications that S.C. injection was more effective than I.N. delivery in eliciting cellular immune responses. Mice vaccinated by either route demonstrated significantly increased virus-specific neutralization antibodies on weeks 8 and 12 compared to control groups, as well as BM antibody forming cells (AFC), indicative of long-term immunity. Thus, this Ad5-vectored SARS-CoV-2 vaccine candidate showed promising immunogenicity following delivery to mice by S.C. and I.N. routes of administration, supporting the further development of Ad-based vaccines against COVID-19 and other infectious diseases for sustainable global immunization programs.</p
“I showed you what i thought was appropriate”
No full textThis article highlights some aspects of doing longitudinal ethnography in criminology. By zooming in and reflecting on some of the key moments and methodological choices made over the course of more than 15 years of fieldwork among members of a Dutch gang, this article illustrates that relations with informants have the potential to strengthen over time, but that building rapport and trust with (active) offenders is not necessarily a linear process. In addition to voicing the emotional and evocative aspects of these methodological deliberations, this “true confession” is meant to spark some more debate on how longitudinal fieldwork in criminology impacts field relations by critically examining not only the performativity of informants, but also of researchers.</p
A Propensity Score Matched Approach to Assess the Associations of Commonly Prescribed Medications with Fall Risk in a Large Harmonized Cohort of Older Ambulatory Persons
No full textIntroduction: Several medication classes are considered to present risk factors for falls. However, the evidence is mainly based on observational studies that often lack adequate adjustment for confounders. Therefore, we aimed to assess the associations of medication classes with fall risk by carefully selecting confounders and by applying propensity score matching (PSM). Methods: Data from several European cohorts, harmonized into the ADFICE_IT cohort, was used. Our primary outcome was time until the first fall within 1-year follow-up. The secondary outcome was a fall in the past year. Our exposure variables were commonly prescribed medications. We used 1:1 PSM to match the participants with reported intake of specific medication classes with participants without. We constructed Cox regression models stratified by the pairs matched on the propensity score for our primary outcome and conditional logistic regression models for our secondary outcome. Results: In total, 32.6% of participants fell in the 1-year follow-up and 24.4% reported falling in the past year. ACE inhibitor users (prevalence of use 15.3%) had a lower fall risk during follow-up when matched to non-users, with a hazard ratio (HR) of 0.82 (95% CI 0.68–0.98). Also, statin users (prevalence of use 20.1%) had a lower risk, with an HR of 0.76 (95% CI 0.65–0.90). Other medication classes showed no association with risk of first fall. Also, in our secondary outcome analyses, statin users had a significantly lower risk. Furthermore, β-blocker users had a lower fall risk and proton pump inhibitor use was associated with a higher risk in our secondary outcome analysis. Conclusion: Many commonly prescribed medication classes showed no associations with fall risk in a relatively healthy population of community-dwelling older persons. However, the treatment effects and risks can be heterogeneous between individuals. Therefore, focusing on identification of individuals at risk is warranted to optimize personalized falls prevention.</p
Use of antithrombotics at the end of life
No full textBackground: Antithrombotics are frequently prescribed for patients with a limited life expectancy. In the last phase of life, when treatment is primarily focused on optimizing patients’ quality of life, the use of antithrombotics should be reconsidered. Methods: We performed a secondary analysis of a retrospective review of 180 medical records of patients who had died of a malignant or non-malignant disease, at home, in a hospice or in a hospital, in the Netherlands. All medication prescriptions and clinical notes of patients using antithrombotics in the last three months of life were reviewed manually. We subsequently developed case vignettes based on a purposive sample, with variation in setting, age, gender, type of medication, and underlying disease. Results: In total 60% (n=108) of patients had used antithrombotics in the last three months of life. Of all patients using antithrombotics 33.3 % died at home, 21.3 % in a hospice and 45.4 % in a hospital. In total, 157 antithrombotic prescriptions were registered; 30 prescriptions of vitamin K antagonists, 60 of heparins, and 66 of platelet aggregation inhibitors. Of 51 patients using heparins, 32 only received a prophylactic dose. In 75.9 % of patients antithrombotics were continued until the last week before death. Case vignettes suggest that inability to swallow, bleeding complications or the dying phase were important factors in making decisions about the use of antithrombotics. Conclusions: Antithrombotics in patients with a life limiting disease are often continued until shortly before death. Clinical guidance may support physicians to reconsider (dis)continuation of antithrombotics and discuss this with the patient.</p