Pain and fatigue in adult patients with multiple osteochondromas: The Netherlands.

BACKGROUND: Multiple Osteochondromas (MO) is a rare genetic disorder characterised by the presence of numerous benign bone tumours, known as osteochondromas. Within the spectrum of debilitating symptoms associated with MO, pain is recognized as a major problem. Interestingly, our clinical observations suggest that fatigue is also a significant concern but has merely been touched upon in MO literature. This study aims to (1) assess the level of pain and fatigue in adult patients with MO; (2) compare fatigue in MO to healthy subjects and patients with Rheumatoid Arthritis (RA); (3) identify associated variables for pain and fatigue in patients with MO. METHODS: In this cross-sectional study, 353 adult MO patients completed a survey with validated questionnaires on pain, fatigue and psychosocial factors. Pain and fatigue were assessed with the Numeric Rating Scale (NRS), and fatigue was also measured with the Checklist Individual Strength (CIS). Fatigue (CIS) was compared with reference scores of healthy subjects and patients with RA, using a one-sample t-test. Multiple linear regression models for pain and fatigue were developed using a-priori selected independent variables based on a theoretical framework (ICF-model). RESULTS: Pain was reported by 87.8% (NRS = 3.19±2.6) and fatigue by 90.4% (NRS = 4.1±2.6) of patients with MO. Fatigue scores for MO (CIS = 84.1±15.3) were significantly higher (p<0.001) compared to reference scores of healthy subjects and patients with RA. The multivariable analysis for pain provided a final regression model with six variables (R2 = 0.445, p<0.001) of which fear avoidance beliefs and fatigue had the strongest association. For the fatigue models NRS (R2 = 0.455, p<0.001) and CIS (R2 = 0.233, p<0.001), the strongest associations were found with anxiety and depression respectively. CONCLUSIONS: Pain and fatigue are highly prevalent in patients with MO. Fatigue is significantly higher compared to healthy subjects and patients with RA. Several variables associated with pain and fatigue have been identified that could help improve multidisciplinary treatment plans.

A high-volume study on the impact of diabetes mellitus on clinical outcomes after surgical and percutaneous cardiac interventions.

BACKGROUND: Type I and type II diabetes mellitus (DM) patients have a higher prevalence of cardiovascular diseases, as well as a higher mortality risk of cardiovascular diseases and interventions. This study provides an update on the impact of DM on clinical outcomes, including mortality, complications and reinterventions, using data on percutaneous and surgical cardiac interventions in the Netherlands. METHODS: This is a retrospective, nearby nationwide study using real-world observational data registered by the Netherlands Heart Registration (NHR) between 2015 and 2020. Patients treated for combined or isolated coronary artery disease (CAD) and aortic valve disease (AVD) were studied. Bivariate analyses and multivariate logistic regression models were used to evaluate the association between DM and clinical outcomes both unadjusted and adjusted for baseline characteristics. RESULTS: 241,360 patients underwent the following interventions; percutaneous coronary intervention(N = 177,556), coronary artery bypass grafting(N = 39,069), transcatheter aortic valve implantation(N = 11,819), aortic valve replacement(N = 8,028) and combined CABG and AVR(N = 4,888). The incidence of DM type I and II was 21.1%, 26.7%, 17.8%, 27.6% and 27% respectively. For all procedures, there are statistically significant differences between patients living with and without diabetes, adjusted for baseline characteristics, at the expense of patients with diabetes for 30-days mortality after PCI (OR = 1.68; p <.001); 120-days mortality after CABG (OR = 1.35; p <.001), AVR (OR = 1.5; p <.03) and CABG + AVR (OR = 1.42; p =.02); and 1-year mortality after CABG (OR = 1.43; p <.001), TAVI (OR = 1.21; p =.01) and PCI (OR = 1.68; p <.001). CONCLUSION: Patients with DM remain to have unfavourable outcomes compared to nondiabetic patients which calls for a critical reappraisal of existing care pathways aimed at diabetic patients within the cardiovascular field.

Benzodiazepine use in relation to long-term dementia risk and imaging markers of neurodegeneration: a population-based study.

BACKGROUND: Benzodiazepine use is common, particularly in older adults. Benzodiazepines have well-established acute adverse effects on cognition, but long-term effects on neurodegeneration and dementia risk remain uncertain. METHODS: We included 5443 cognitively healthy (MMSE ≥ 26) participants from the population-based Rotterdam Study (57.4% women, mean age 70.6 years). Benzodiazepine use from 1991 until baseline (2005-2008) was derived from pharmacy dispensing records, from which we determined drug type and cumulative dose. Benzodiazepine use was defined as prescription of anxiolytics (ATC-code: N05BA) or sedative-hypnotics (ATC-code: N05CD) between inception of pharmacy records and study baseline. Cumulative dose was calculated as the sum of the defined daily doses for all prescriptions. We determined the association with dementia risk until 2020 using Cox regression. Among 4836 participants with repeated brain MRI, we further determined the association of benzodiazepine use with changes in neuroimaging markers using linear mixed models. RESULTS: Of all 5443 participants, 2697 (49.5%) had used benzodiazepines at any time in the 15 years preceding baseline, of whom 1263 (46.8%) used anxiolytics, 530 (19.7%) sedative-hypnotics, and 904 (33.5%) used both; 345 (12.8%) participants were still using at baseline assessment. During a mean follow-up of 11.2 years, 726 participants (13.3%) developed dementia. Overall, use of benzodiazepines was not associated with dementia risk compared to never use (HR [95% CI]: 1.06 [0.90-1.25]), irrespective of cumulative dose. Risk estimates were somewhat higher for any use of anxiolytics than for sedative-hypnotics (HR 1.17 [0.96-1.41] vs 0.92 [0.70-1.21]), with strongest associations for high cumulative dose of anxiolytics (HR [95% CI] 1.33 [1.04-1.71]). In imaging analyses, current use of benzodiazepine was associated cross-sectionally with lower brain volumes of the hippocampus, amygdala, and thalamus and longitudinally with accelerated volume loss of the hippocampus and to a lesser extent amygdala. However, imaging findings did not differ by type of benzodiazepines or cumulative dose. CONCLUSIONS: In this population-based sample of cognitively healthy adults, overall use of benzodiazepines was not associated with increased dementia risk, but potential class-dependent adverse effects and associations with subclinical markers of neurodegeneration may warrant further investigation.

Exploring psychosocial vulnerability among Dutch pregnant women: a register study.

In the Netherlands adverse perinatal outcomes are also associated with non-medical factors which vary across geographical locations. This study analyses the presence of non-medical vulnerabilities in pregnant women in two regions with high numbers of psychosocial adversity using the same definition for vulnerability in both regions. A register study was performed in 2 regions. Files from women in midwife-led care were analyzed using a standardized case report form addressing non-medical vulnerability based on the Rotterdam definition for vulnerability: measurement A in Groningen (n = 500), measurement B in South-Limburg (n = 538). Only in South-Limburg a second measurement was done after implementing an identification tool for vulnerability (C (n = 375)). In both regions about 10% of pregnant women had one or more urgent vulnerabilities and almost all of these women had an accumulation of several urgent and non-urgent vulnerabilities. Another 10% of women had an accumulation of three or more non-urgent vulnerabilities. This study showed that by using the Rotterdam definition of vulnerability in both regions about 20% of pregnant women seem to live in such a vulnerable situation that they may need psychosocial support. The definition seems a good tool to determine vulnerability. However, without considering protective factors it is difficult to establish precisely women's vulnerability. Research should reveal whether relevant women receive support and whether this approach contributes to better perinatal and child outcomes.

The Fading of the Mpox Outbreak Among Men Who Have Sex With Men: A Mathematical Modelling Study.

BACKGROUND: In the Netherlands, the number of mpox cases started declining before mpox vaccination was initiated. Most cases were men who have sex with men (MSM). We investigated whether the decline in mpox could be attributed to infection-induced immunity or behavioral adaptations. METHODS: We developed a transmission model and accounted for possible behavioral adaptations: fewer casual partners and shorter time until MSM with mpox refrain from sexual contacts. RESULTS: Without behavioral adaptations, the peak in modelled cases matched observations, but the decline was less steep than observed. With behavioral adaptations in the model, we found a decline of 16%-18% in numbers of casual partners in June and 13%-22% in July 2022. Model results showed a halving of the time before refraining from sex. When mpox vaccination started, 57% of MSM with very high sexual activity in the model had been infected. Model scenarios revealed that the outbreak could have waned by November 2022 even without vaccination. CONCLUSIONS: The limited duration of the mpox outbreak in the Netherlands can be ascribed primarily to infection-induced immunity among MSM with high sexual activity levels. The decline was accelerated by behavioral adaptations. Immunity among those most sexually active is essential to impede mpox resurgence.

Mortality Rates of the Spanish Flu and Coronavirus Disease 2019 in the Netherlands: A Historical Comparison.

The coronavirus disease 2019 (COVID-19) pandemic has been called the deadliest disease event in history. In this study, we compared the cause-specific mortality rate of the Spanish flu (1918-1920) with that of COVID-19 (2020-2022) in the Netherlands. During the periods of exposure, about 50 000 people died of COVID-19 and 32 000 people of the Spanish flu. In absolute numbers, COVID-19 seems to be deadlier than Spanish flu. However, the crude mortality rates for COVID-19 and Spanish flu were 287 and 486 per 100 000 inhabitants, respectively. Comparing age-standardized mortality rates, there would have been 28 COVID-19- and 194 Spanish flu-related deaths in 1918-1920, or 214 Spanish flu- and 98 COVID-19-related deaths in 2020-2022 per 100 000 inhabitants per year. Thus, taking the population differences into account, the Spanish flu would have been deadlier than COVID-19.

Comparing healthcare systems between the Netherlands and Australia in management for children with acute gastroenteritis.

BACKGROUND: Acute gastroenteritis is a highly contagious disease demanding effective public health and clinical care systems for prevention and early intervention to avoid outbreaks and symptom deterioration. The Netherlands and Australia are both top-performing, high-income countries where general practitioners (GPs) act as healthcare gatekeepers. However, there is a lower annual incidence and per-case costs for childhood gastroenteritis in Australia. Understanding the systems and policies in different countries can lead to improvements in processes and care. Therefore, we aimed to compare public health systems and clinical care for children with acute gastroenteritis in both countries. METHODS: A cross-country expert study was conducted for the Netherlands and Australia. Using the Health System Performance Assessment framework and discussions within the research group, two questionnaires (public health and clinical care) were developed. Questionnaires were delivered to local experts in the Netherlands and the state of Victoria, Australia. Data synthesis employed a narrative approach with constant comparison. RESULTS: In Australia, rotavirus vaccination is implemented in a national program with immunisation requirements and legislation for prevention, which is not the case in the Netherlands. Access to care differs, as Dutch children must visit their regular GP before the hospital, while in Australia, children have multiple options and can go directly to hospital. Funding varies, with the Netherlands providing fully funded healthcare for children, whilst in Australia it depends on which GP (co-payment required or not) and hospital (public or private) they visit. Additionally, the guideline-recommended dosage of the antiemetic ondansetron is lower in the Netherlands. CONCLUSIONS: Healthcare approaches for managing childhood gastroenteritis differ between the Netherlands and Australia. The lower annual incidence and per-case costs for childhood gastroenteritis in Australia cannot solely be explained by the differences in healthcare system functions. Nevertheless, Australia's robust public health system, characterized by legislation for vaccinations and quarantine, and the Netherland's well-established clinical care system, featuring fully funded continuity of care and lower ondansetron dosages, offer opportunities for enhancing healthcare in both countries.

TAPS-tool reveals severe under detection of substance use problems in patients with severe mental illness.

INTRODUCTION: Substance use disorders (SUD) and associated problems are highly prevalent but often undetected in patients with Severe Mental Illness (SMI). This study investigates the prevalence, under-detection, and variables associated with a high risk of SUD in a Dutch sample of adult outpatient SMI patients (N = 83). METHODS: Substance use (The Tobacco, Alcohol, Prescription medication, and other Substance use -TAPS-tool), quality of life (Manchester Short Assessment of Quality of Life-MANSA), general functioning (Health of the Nation Outcome Scale-HoNOS), DSM-5 classifications and patient characteristics (age, education, marital status) were assessed. Detection of SUD was determined by calculating % agreement of DSM-5 classification to TAPS outcome. A logistic regression analysis was performed to determine the association of patient characteristics, quality of life and general functioning to an increased risk of SUD as determined by the TAPS. RESULTS: Concerning prevalence, 89% of the patients used tobacco, above guideline-recommended daily limits of alcohol, illicit drugs or prescription medications for nonmedical purposes. Almost all smokers, half of the alcohol users and three-quarter of the patients that use marihuana or stimulant drugs had a high risk of SUD. All patients with high risk of SUD associated with alcohol, drugs or medications also had SUD associated with tobacco use. Concerning under detection less than half of the patients with a high risk of SUD according the TAPS had a SUD in their DSM-5 classification. Gender, partner, age and satisfaction about the relationship with family had a significant association with a high risk of SUD. CONCLUSIONS: Screening for addiction in an SMI sample with the TAPS-tool revealed a high prevalence of substance use and a high risk of SUD. TAPS outcomes compared to the clinically obtained DSM-5 classification revealed a high degree of under-detection of substance use problems. Smoking seems to pose a specific additional risk of addiction and deserves more attention in treatment to achieve greater health care benefits.

Investigating Users' Attitudes Toward Automated Smartwatch Cardiac Arrest Detection: Cross-Sectional Survey Study.

Background: Out-of-hospital cardiac arrest (OHCA) is a leading cause of mortality in the developed world. Timely detection of cardiac arrest and prompt activation of emergency medical services (EMS) are essential, yet challenging. Automated cardiac arrest detection using sensor signals from smartwatches has the potential to shorten the interval between cardiac arrest and activation of EMS, thereby increasing the likelihood of survival. Objective: This cross-sectional survey study aims to investigate users' perspectives on aspects of continuous monitoring such as privacy and data protection, as well as other implications, and to collect insights into their attitudes toward the technology. Methods: We conducted a cross-sectional web-based survey in the Netherlands among 2 groups of potential users of automated cardiac arrest technology: consumers who already own a smartwatch and patients at risk of cardiac arrest. Surveys primarily consisted of closed-ended questions with some additional open-ended questions to provide supplementary insight. The quantitative data were analyzed descriptively, and a content analysis of the open-ended questions was conducted. Results: In the consumer group (n=1005), 90.2% (n=906; 95% CI 88.1%-91.9%) of participants expressed an interest in the technology, and 89% (n=1196; 95% CI 87.3%-90.7%) of the patient group (n=1344) showed interest. More than 75% (consumer group: n= 756; patient group: n=1004) of the participants in both groups indicated they were willing to use the technology. The main concerns raised by participants regarding the technology included privacy, data protection, reliability, and accessibility. Conclusions: The vast majority of potential users expressed a strong interest in and positive attitude toward automated cardiac arrest detection using smartwatch technology. However, a number of concerns were identified, which should be addressed in the development and implementation process to optimize acceptance and effectiveness of the technology.

Validity of the five-item mental health inventory for screening current mood and anxiety disorders in the general population.

OBJECTIVES: The Mental Health Inventory (MHI-5) is frequently used as a screener for mood and anxiety disorders. However, few population-based studies have validated it against a diagnostic instrument assessing disorders following current diagnostic criteria. METHODS: Within the third Netherlands Mental Health Survey and Incidence Study (NEMESIS-3), a representative population-based study of adults (N = 6194; age: 18-75 years), the MHI-5 was used to measure general mental ill-health in the past month. Presence of mood (major depressive disorder, persistent depressive disorder, or bipolar disorder) and anxiety disorders (panic disorder, agoraphobia, social phobia, or generalized anxiety disorder) in the past month was assessed with a slightly modified version of the Composite International Diagnostic Interview 3.0 per the Diagnostic and Statistical Manual of Mental disorders-5. RESULTS: The MHI-5 was good to excellent at distinguishing people with and without a mood disorder, an anxiety disorder, and any mood or anxiety disorder. The cut-off value associated with the highest sensitivity and highest specificity for mood disorder was ≤68, and ≤76 for an anxiety disorder or any mood or anxiety disorder. CONCLUSIONS: The MHI-5 can identify individuals at high risk of a current mood or anxiety disorder in the general population when diagnostic interviews are too time consuming.

Use of proxy indicators for automated surveillance of severe acute respiratory infection, the Netherlands, 2017 to 2023: a proof-of-concept study.

BackgroundEffective pandemic preparedness requires robust severe acute respiratory infection (SARI) surveillance. However, identifying SARI patients based on symptoms is time-consuming. Using the number of reverse transcription (RT)-PCR tests or contact and droplet precaution labels as a proxy for SARI could accurately reflect the epidemiology of patients presenting with SARI.AimWe aimed to compare the number of RT-PCR tests, contact and droplet precaution labels and SARI-related International Classification of Disease (ICD)-10 codes and evaluate their use as surveillance indicators.MethodsPatients from all age groups hospitalised at Leiden University Medical Center between 1 January 2017 up to and including 30 April 2023 were eligible for inclusion. We used a clinical data collection tool to extract data from electronic medical records. For each surveillance indicator, we plotted the absolute count for each week, the incidence proportion per week and the correlation between the three surveillance indicators.ResultsWe included 117,404 hospital admissions. The three surveillance indicators generally followed a similar pattern before and during the COVID-19 pandemic. The correlation was highest between contact and droplet precaution labels and ICD-10 diagnostic codes (Pearson correlation coefficient: 0.84). There was a strong increase in the number of RT-PCR tests after the start of the COVID-19 pandemic.DiscussionAll three surveillance indicators have advantages and disadvantages. ICD-10 diagnostic codes are suitable but are subject to reporting delays. Contact and droplet precaution labels are a feasible option for automated SARI surveillance, since these reflect trends in SARI incidence and may be available real-time.

Development of the DONOR prediction model on the risk of hypertensive complications in oocyte donation pregnancy: study protocol for a multicentre cohort study in the Netherlands.

INTRODUCTION: Oocyte donation (OD) pregnancy is accompanied by a high incidence of hypertensive complications, with serious consequences for mother and child. Optimal care management, involving early recognition, optimisation of suitable treatment options and possibly eventually also prevention, is in high demand. Prediction of patient-specific risk factors for hypertensive complications in OD can provide the basis for this. The current project aims to establish the first prediction model on the risk of hypertensive complications in OD pregnancy. METHODS AND ANALYSIS: The present study is conducted within the DONation of Oocytes in Reproduction project. For this multicentre cohort study, at least 541 OD pregnancies will be recruited. Baseline characteristics and obstetric data will be collected. Additionally, one sample of maternal peripheral blood and umbilical cord blood after delivery or a saliva sample from the child will be obtained, in order to determine the number of fetal-maternal human leucocyte antigen mismatches. Following data collection, a multivariate logistic regression model will be developed for the binary outcome hypertensive complication 'yes' and 'no'. The Prediction model Risk Of Bias ASsessment Tool will be used as guide to minimise the risk of bias. The study will be reported in line with the 'Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis' guideline. Discrimination and calibration will be determined to assess model performance. Internal validation will be performed using the bootstrapping method. External validation will be performed with the 'DONation of Oocytes in Reproduction individual participant data' dataset. ETHICS AND DISSEMINATION: This study is approved by the Medical Ethics Committee LDD (Leiden, Den Haag, Delft), with protocol number P16.048 and general assessment registration (ABR) number NL56308.058.16. Further results will be shared through peer-reviewed journals and international conferences.

Inflammatory profiles are associated with long COVID up to 6 months after COVID-19 onset: A prospective cohort study of individuals with mild to critical COVID-19.

BACKGROUND: After initial COVID-19, immune dysregulation may persist and drive post-acute sequelae of COVID-19 (PASC). We described longitudinal trajectories of cytokines in adults up to 6 months following SARS-CoV-2 infection and explored early predictors of PASC. METHODS: RECoVERED is a prospective cohort of individuals with laboratory-confirmed SARS-CoV-2 infection between May 2020 and June 2021 in Amsterdam, the Netherlands. Serum was collected at weeks 4, 12 and 24 of follow-up. Monthly symptom questionnaires were completed from month 2 after COVID-19 onset onwards; lung diffusion capacity (DLCO) was tested at 6 months. Cytokine concentrations were analysed by human magnetic Luminex screening assay. We used a linear mixed-effects model to study log-concentrations of cytokines over time, assessing their association with socio-demographic and clinical characteristics that were included in the model as fixed effects. RESULTS: 186/349 (53%) participants had ≥2 serum samples and were included in current analyses. Of these, 101/186 (54%: 45/101[45%] female, median age 55 years [IQR = 45-64]) reported PASC at 12 and 24 weeks after COVID-19 onset. We included 37 reference samples (17/37[46%] female, median age 49 years [IQR = 40-56]). In a multivariate model, PASC was associated with raised CRP and abnormal diffusion capacity with raised IL10, IL17, IL6, IP10 and TNFα at 24 weeks. Early (0-4 week) IL-1ß and BMI at COVID-19 onset were predictive of PASC at 24 weeks. CONCLUSIONS: Our findings indicate that immune dysregulation plays an important role in PASC pathogenesis, especially among individuals with reduced pulmonary function. Early IL-1ß shows promise as a predictor of PASC.

The impact of baseline health factors on second primary cancer risk after radiotherapy for prostate cancer.

PURPOSE: In evaluating second primary cancers (SPCs) following External Beam Radiotherapy (EBRT), the role of lifestyle factors is frequently not considered due to data limitations. We investigated the association between smoking, comorbidities, and SPC risks within EBRT-treated patients for localized prostate cancer (PCa). PATIENTS & METHODS: The study included 1,883 PCa survivors aged 50-79, treated between 2006 and 2013, with intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT). Clinical data were combined with SPC and survival data from the Netherlands Cancer Registry with a 12-month latency period. Standardized Incidence Ratios (SIRs) were calculated comparing the EBRT cohort with the general Dutch population. To explore the effect of patient and treatment characteristics on SPCs we conducted a Cox regression analysis. Lastly, we estimated cumulative incidences of developing solid SPC, pelvis SPC, and non-pelvis SPC using a competing risk analysis. RESULTS: Significantly increased SIRs were observed for all SPC (SIR = 1.21, 95% confidence interval [CI]: 1.08-1.34), pelvis SPC (SIR = 1.46, 95% CI: 1.18-1.78), and non-pelvis SPC (SIR = 1.18, 95% CI [1.04-1.34]). Smoking status was significantly associated with pelvic and non-pelvic SPCs. Charlson comorbidity index (CCI) ≥ 1 (Hazard Ratio [HR] = 1.45, 95% CI: 1.10-1.91), cardiovascular disease (HR = 1.41, 95% CI: 1.05-1.88), and chronic obstructive pulmonary disease (COPD) (HR = 1.91, 95% CI: 1.30-2.79) were significantly associated with non-pelvis SPC. The proportion of active smoking numbers in the cohort was similar to the general population. INTERPRETATION: We conclude that the presence of comorbidities in the EBRT population might be a relevant factor in observed excess non-pelvis SPC risk, but not for excess pelvis SPC risk.

Nosocomial transmission of tet(x3), bla NDM-1 and bla OXA-97-carrying Acinetobacter baumannii conferring resistance to eravacycline and omadacycline, the Netherlands, March to August 2021.

Carbapenem-resistant Acinetobacter baumannii (CRAb) is an important pathogen causing serious nosocomial infections. We describe an outbreak of CRAb in an intensive care unit in the Netherlands in 2021. During an outbreak of non-resistant A. baumannii, while infection control measures were in place, CRAb isolates carrying highly similar bla NDM-1 - and tet(x3)-encoding plasmids were isolated from three patients over a period of several months. The chromosomal and plasmid sequences of the CRAb and non-carbapenemase-carrying A. baumannii isolates cultured from patient materials were analysed using hybrid assemblies of short-read and long-read sequences. The CRAb isolates revealed that the CRAb outbreak consisted of two different strains, carrying similar plasmids. The plasmids contained multiple antibiotic resistance genes including the tetracycline resistance gene tet(x3), and the bla NDM-1 and bla OXA-97 carbapenemase genes. We determined minimal inhibitory concentrations (MICs) for 13 antibiotics, including the newly registered tetracycline antibiotics eravacycline and omadacycline. The CRAb isolates showed high MICs for tetracycline antibiotics including eravacycline and omadacycline, except for minocycline which had a low MIC. In this study we show the value of sequencing multidrug-resistant A. baumannii for outbreak tracking and guiding outbreak mitigation measures.

Intercurrent infection as a risk factor for disease flares in patients with systemic lupus erythematosus.

OBJECTIVE: To determine whether intercurrent infections are a risk factor for subsequent disease flares in systemic lupus erythematosus (SLE). METHODS: Demographic and clinical characteristics of 203 patients with SLE participating in the Amsterdam SLE cohort were collected at baseline and during follow-up. Collection of data on infections and SLE flares was registry-based and infections and flares were categorised as minor or major, based on predefined criteria. Proportional hazard models with recurrent events and time-varying covariates were used to estimate the HR of SLE flares. RESULTS: The incidence rates of major and minor infections were 5.3 per 100 patient years and 63.9 per 100 patient years, respectively. The incidence rates of flares were 3.6 and 15.1 per 100 patient years for major flares and minor flares, respectively.In the proportional hazard model, intercurrent infections (major and minor combined) were associated with the occurrence of SLE flares (major and minor combined; HR 1.9, 95% CI: 1.3 to 2.9). The hazard ratio for a major SLE flare following a major infection was 7.4 (95% CI: 2.2 to 24.6). Major infections were not associated with the occurrence of minor flares. CONCLUSIONS: The results of the present study show that intercurrent infections are associated with subsequent SLE flares, which supports the hypothesis that infections may trigger SLE flares.

Temporal dynamics of depressive symptoms and cognitive decline in the oldest old: dynamic time warp analysis of the Leiden 85-plus study.

BACKGROUND: The prevalence of depressive symptoms and cognitive decline increases with age. We investigated their temporal dynamics in individuals aged 85 and older across a 5-year follow-up period. METHODS: Participants were selected from the Leiden 85-plus study and were eligible if at least three follow-up measurements were available (325 of 599 participants). Depressive symptoms were assessed at baseline and at yearly assessments during a follow-up period of up to 5 years, using the 15-item Geriatric Depression Scale (GDS-15). Cognitive decline was measured through various tests, including the Mini Mental State Exam, Stroop test, Letter Digit Coding test and immediate and delayed recall. A novel method, dynamic time warping analysis, was employed to model their temporal dynamics within individuals, in undirected and directed time-lag analyses, to ascertain whether depressive symptoms precede cognitive decline in group-level aggregated results or vice versa. RESULTS: The 325 participants were all 85 years of age at baseline; 68% were female, and 45% received intermediate to higher education. Depressive symptoms and cognitive functioning significantly covaried in time, and directed analyses showed that depressive symptoms preceded most of the constituents of cognitive impairment in the oldest old. Of the GDS-15 symptoms, those with the strongest outstrength, indicating changes in these symptoms preceded subsequent changes in other symptoms, were worthlessness, hopelessness, low happiness, dropping activities/interests, and low satisfaction with life (all P's < 0.01). CONCLUSION: Depressive symptoms preceded cognitive impairment in a population based sample of the oldest old.

Significant increase in the number of occupational exposures reported to the Dutch Poisons Information Centre (2016-2022): the importance of poison centre data in health surveillance.

INTRODUCTION: Exposure to hazardous substances in the workplace can result in injuries and fatalities. This study aimed to investigate the characteristics and trend of occupational exposures reported to the Dutch Poisons Information Centre and to investigate whether the COVID-19 pandemic had an impact on the trend. METHODS: A retrospective analysis of all acute occupational exposures reported to the Dutch Poisons Information Centre between 1 January 2016 and 31 December 2022 was performed. Data on patient and exposure characteristics, symptoms and treatment recommendations were analyzed. RESULTS: Between 2016 and 2022, the Dutch Poisons Information Centre received 5,508 calls regarding acute occupational exposures. The annual number of calls on acute occupational exposures almost doubled over the years studied (from 475 in 2016 to 936 in 2022). During and after the COVID-19 pandemic (March 2020-December 2022), the number of calls stabilized, but the upward trend was not significantly affected. There were an estimated 0.20 calls per 1,000 human exposure calls per month (95 per cent confidence interval: -0.14; 0.53). Victims were often exposed through multiple routes, with inhalation being the most common route (44 per cent), followed by ocular (32 per cent) and dermal contact (30 per cent). Acids (1,138 exposures) and alkalis (912 exposures) were often involved. The Dutch Poisons Information Centre had information on 6,334 patients, although the total number of exposed patients was not known as some victims did not seek medical assistance, or were treated by healthcare professionals who did not consult our Centre. At the time of contact, 13 per cent (n = 795) of the patients reported no symptoms, 76 per cent (n = 4,805) reported mild to moderate symptoms and 3 per cent (n = 183) reported potentially severe symptoms. Information on symptoms was missing for 9 per cent (n = 551) of the patients. Hospital observation and treatment were recommended for 5 per cent (n = 325) of the patients. DISCUSSION: This study highlights the necessity for poisoning prevention strategies to reduce the number of work-related incidents involving hazardous substances. CONCLUSION: The continuing increase in the number of workplace incidents involving hazardous substances is of concern. A comprehensive and multidisciplinary approach should be taken to gain a full understanding of occupational exposure to hazardous substances and to identify risk factors.

Pulmonary function trajectories in COVID-19 survivors with and without pre-existing respiratory disease.

A significant proportion of COVID-19 survivors still experience a reduced diffusion capacity three and twelve months after discharge. We aimed to compare pulmonary function trajectories between hospitalized COVID-19 patients with pre-existing respiratory disease (PRD) and patients without pre-existing respiratory disease (Non-PRD) at three and twelve months after hospital discharge. This single-centre retrospective cohort study included COVID-19 patients admitted to the VieCuri Medical Centre (Venlo, the Netherlands) between February and December 2020 that were invited to the outpatient clinic at three and twelve months after discharge. During this visit, pulmonary function tests were performed and impairments were based on lower limit of normal. Data of 239 patients were analysed (65% male, 66 ± 10 years, and 26% with a history of respiratory disease). Three months after discharge, 49% and 64% of the Non-PRD patients (n = 177) and PRD patients (n = 62) had a low diffusion capacity, respectively. This improved over time in Non-PRD patients (p = 0.003), but not in PRD patients (p = 0.250). A low diffusion capacity was still observed in 34% and 57% of the Non-PRD and PRD group, respectively, twelve months after discharge. Pulmonary function impairments, mainly a reduced diffusion capacity, are observed among hospitalized COVID-19 patients with PRD and Non-PRD, at three and twelve months follow-up. Although diffusion capacity impairments restore over time in Non-PRD patients, poor recovery was observed among PRD patients.

The Elecsys® Anti-SARS-CoV-2 and Elecsys® Anti-SARS-CoV-2 S antibody assays: Differentiating between vaccination and infection, and assessing long-term performance.

INTRODUCTION: Serological surveillance is useful for assessing SARS-CoV-2 immunity in populations. To effectively study the presence and persistence of antibodies, it is necessary to distinguish between persons with past infection, and persons who only received vaccination. Knowledge of the duration of antibody persistence is essential for correct interpretation of surveillance results. METHODS: Starting in April 2020, waning of SARS-CoV-2 antibodies was studied in a longitudinal cohort study of 495 SARS-CoV-2 antibody-positive Dutch blood donors, not pre-selected by PCR testing or disease severity. Additionally, in May 2021, a sample of donors representative for the Dutch population was tested for antibodies against the SARS-CoV-2 spike (S) protein, using the Wantai Ab ELISA and the Elecsys® Anti-SARS-CoV-2 S assay; and for antibodies against the nucleocapsid protein, which indicate past infection, using the Elecsys® Anti-SARS-CoV-2 assay. RESULTS: The anti-S response in donors that were infected in April or May 2020 remained positive in 100% of donors in the Elecsys® Anti-SARS-CoV-2 S assay one year after infection, after which follow up of waning was no longer possible because of large scale vaccination. The anti-nucleocapsid response results were still positive in approximately 80% of donors two years after infection. In May 2021, 51% of the donors showed anti-S reactivity and 16.8% tested positive for anti-nucleocapsid antibodies. CONCLUSION: Infection with SARS-CoV-2 resulted in spike and nucleocapsid antibody levels still detectable in the majority of donors 1-2 years after infection. In May 2021, 51% of donors were vaccinated and 16.8% had had an infection. Thus, both Elecsys® SARS-CoV-2 antibody assays can be used to reliably assess the vaccination and infection status of individuals.