Netherlands Center for Occupational Diseases

ABSTRACTThis prospective study assessed the prevalence, type, and consequences of persistent symptoms following a nonhospitalized SARS‐CoV‐2 infection by comparing infected and noninfected children and adults of Dutch households. Two comparable prospective household studies were conducted during two pandemic phases. At baseline, all household members were tested for SARS‐CoV‐2 with 10 consecutive saliva samples during a 6‐week period using RT‐PCR. Questionnaires assessing persistent symptoms, health‐related quality of life (HRQoL), anxiety, and depressive symptoms were collected at 6 and 12 months. Of the 297 included participants (median age 34 years, IQR 12–48), 201 (67.7%) tested positive for SARS‐CoV‐2. At 6 months, only one child reported persistent symptoms. SARS‐CoV‐2‐infected adults (> 18 years) reported more pulmonary symptoms (15.2% vs. 3.4%, p = 0.023), and tended to report more fatigue (12.8% vs. 3.4%, p = 0.061) and exertion‐related symptoms (8.8% vs. 1.7%, p = 0.107) compared to the negative adults. Adult participants with persistent symptoms reported decreased HRQoL and increased anxiety and depressive symptoms. This study found that SARS‐CoV‐2‐positive adults tended to have higher prevalence of respiratory symptoms, fatigue, and exertion‐related symptoms 6 months after SARS‐CoV‐2 infection, whereas children rarely reported persistent symptoms. Persistent symptoms were associated with a reduced HRQoL and increased anxiety and depression.

Starting antiretroviral treatment (ART) at higher CD4 cell counts is associated with reduced non-AIDS-defining malignancy (NADM) risk. We studied whether starting ART within 1 year after acquiring HIV reduces this risk while also adjusting for socio-economic status. We included individuals (≥18 years) from the Dutch national ATHENA cohort diagnosed with HIV-1 and having started ART between 2000-2022 without prior NADM with ≥6 months of follow-up. 'Early ART' initiators were defined as starting ART <365 days following a negative HIV test or primary HIV infection, all others as 'late-ART' starters. Hazard Ratios (HR) for NADM were estimated using Cox regression, adjusted for a priori selected confounders (age, sex at birth, smoking, alcohol use, calendar time, HIV transmission route, region of origin, nadir CD4 cell count, HIV-1 viral copy-years) and socio-economic status (SES) using data from Statistics Netherlands. Compared to 'late-ART' (n=17,965) participants, 'early-ART' participants (n=1,858) were younger (median 34.8 vs. 39.0 years), with a higher nadir CD4 count (median 478 vs. 260 cells/µl).. NADM were diagnosed in 25 'early-ART' and 869 'late-ART' starters resulting in an incidence rate of 2.22/1000 person-years (PY) (95% confidence interval (CI)=1.50-3.28) and 4.87/1000 PY (95%CI=4.56-5.21), respectively. 'Early-ART' initiation was associated with a reduced risk of any NADM (HR=0.60 [95%CI=0.40-0.91]) and infection-unrelated NADM (HR=0.60 [95%CI=0.37-0.98]), but not of infection-related NADM (HR=0.58 [95%CI=0.27-1.28]). Additional adjustment for SES only minimally changed the hazard ratios. Starting ART within one year of HIV acquisition is associated with a reduced NADM risk compared to starting ART later.

Capillary blood microsampling enables the sampling of small blood volumes, making it suitable for vulnerable populations, remote collection, and repeated sampling. Owing to its minimal invasiveness, blood microsampling has emerged as an alternative to venipuncture in many fields. However, as capillary blood differs from venous blood in composition and analytes vary in their distribution between the blood cell and plasma fractions, plasma and capillary blood concentrations may differ. Because plasma is often the standard matrix for routine analyses, this discrepancy can compromise the clinicians' interpretation of capillary blood results. Hence, to ensure comparability with results obtained through plasma-based assays and reference ranges, accurate conversion to plasma concentrations may be required, which may improve the reliability and validity of microsampling-based outcomes. Despite its relevance, guidance on whether conversion is appropriate or desired and on how to translate and validate the translation of capillary blood microsampling results to plasma concentrations is lacking. To address this gap, members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) expert committees have prepared this guideline to discuss the "what, when, and how" of converting capillary to plasma concentrations and provide guidance on the decision of fit-for-purpose conversion. In addition, guidance to assess capillary blood results when the reference matrix is whole blood and to assess liquid capillary plasma results is provided. The included topics, as well as considerations and recommendations presented in this guideline, were based on a previously published dried blood spot-based IATDMCT guideline, literature review and expert opinions of the authors. Key points include the importance of conducting a comprehensive clinical validation study to fully understand capillary blood microsampling results. In addition, the performance of the conversion method should be evaluated case by case, as it depends on both the microsampling-based method and analyte of interest. Furthermore, an independent set of paired capillary and venous samples should be used to validate an established conversion formula. Finally, a key point for future studies is to focus on the clinical impact of (converted) capillary blood concentrations in comparison with decisions based on results in the reference matrix to guarantee any microsampling-based outcome.

The concept of personalized medicine and its significant benefits for patients and society was introduced over three decades ago. The Human Genome Project (initiated in 1990 and completed in 2003) greatly accelerated the development of precision medicine. In many cancers, defined biomarkers are used to select patients for therapy. For example, KRAS mutations are used to guide treatment with Sotorasib, while tumor expression of (wild type) human epidermal growth factor receptor 2 and 3 (HER2 and HER3) are used to select patients for trastuzumab and cetuximab, respectively. Nonetheless, the clinical adoption of companion diagnostics to facilitate a patient-centric approach in inflammatory diseases remains disappointing. One key reason why the development of companion diagnostics may be delayed autoimmune and fibrotic diseases can be the timing when clinical development teams inform R&amp;D teams about relevant biomarkers or companion diagnostic to select patients, disease monitoring or treatment termination decisions. For clinical practicality, it is highly preferred to measure a biomarker in the systemic circulation, as blood samples can be obtained relatively easily in most diseases. However, discovering systemic biomarkers during clinical development has proven extremely challenging. Here, we describe an alternative approach, which we have used to select the most appropriate target for IgA driven autoimmune and fibrotic diseases. In this specific context, autoantigen-specific assays to determine autoantibody serum levels are widely available for a variety of indications. A detailed analysis of the biological pathways that affect the biomarker can uncover multiple potential therapeutic targets, allowing selection of the most optimal target from a clinical development perspective. Identification of a relevant biomarker before clinical development is initiated, enabling patient stratification in early clinical studies. Selection of the appropriate patient population based on biomarker presence reduces the number of patients needed and consequently, clinical development costs. Moreover, such a patient stratification approach minimizes the risk of including patients who are unlikely to respond, thereby avoiding unnecessary adverse events. This approach was applied during the selection of an anti-CD89 antagonist monoclonal antibody for IgA-mediated autoimmune and fibrotic diseases, serving as an illustrative example of this novel strategy.

Spinal cord injury is a severe central nervous system disorder, burdening patients and society. Current treatments, such as early surgeries and corticosteroid therapy, have limited efficacy and potential risks. Moreover, rehabilitation training only offers partial recovery. This review aims to summarize the latest advances in preclinical and clinical research on cutting-edge treatment technologies for spinal cord injury, including neuromodulation, pharmacological strategies, cell therapies, surgical interventions, tissue engineering, and rehabilitation training. Neuromodulation such as brain-computer interfaces restores motor function by decoding neural signals, while epidural spinal cord stimulation combined with rehabilitation training notably enhances motor and autonomic nervous function. In terms of cell therapy, co-transplantation of mesenchymal stem cells and Schwann cells promotes neural repair, while genetically engineered neural progenitor cells enhance regenerative potential through directed differentiation. In addition, the combination of tissue engineering scaffolds and biomaterials offers new ways to repair the neural microenvironment, and hypothalamus-targeted deep brain stimulation markedly improves walking ability in patients with chronic spinal cord injury. Current spinal cord injury treatments are shifting from a single-modality approach to multimodal integration, such as combining neural stimulation with stem cell transplantation and optimizing cell functions through gene editing technologies. Further research is needed to unravel the complex pathological mechanisms of spinal cord injury, advance personalized therapies, and develop artificial intelligence-assisted rehabilitation technologies, ultimately guiding precise neural functional reconstruction and long-term recovery. Multidisciplinary collaboration and technological innovation will be the key to overcoming the current bottlenecks in the treatment of spinal cord injury.

BackgroundMental disorders are relatively common in individuals who undergo metabolic bariatric surgery (MBS). Prior research suggests that mental disorders may relate to increased healthcare use after MBS. We retrospectively explored the association between preoperative mental health disorders and healthcare use in the first postoperative year.MethodsPatients who underwent primary MBS and had a structured preoperative psychological assessment report were included. Data on healthcare use was collected as the total number of non-routine healthcare appointments including inpatient, outpatient, and emergency department visits. Additionally, gastrointestinal (GI) healthcare use at the radiology, gastroenterology, and emergency departments was analyzed separately.ResultsOf the 944 included patients, 261 (28%) had a preoperatively diagnosed mental disorder. Most prevalent were depressive disorders, anxiety disorders, and eating disorders. Patients with a preoperative mental disorder had a 15% (adjusted, CI 1.04–1.27, p = 0.005) higher rate of total healthcare use compared to those without. Among patients who had any GI-related healthcare, those with a mental disorder had a 61% higher rate of GI-related healthcare use (CI 1.02–2.55, p = 0.041). Patients with a mental disorder tended to have 20% lower odds of having no GI-related healthcare appointments (unadjusted, not statistically significant, CI 0.37–1.74, p = 0.568).ConclusionThe presence of preoperative mental disorders was weakly related to higher total non-routine hospital healthcare use in the first year after MBS. Models explained only 5–13% of the variation in appointment frequency, meaning unmeasured and/or unknown factors play a role in healthcare use.

Value-based healthcare delivery focuses on optimizing care provided by measuring the healthcare outcomes which are most important to the clients relative to the total care costs. However, the understanding of what adds value for clients during work disability assessment is lacking. To explore what medical examiners (MEs) perceive as valuable during the work disability assessment process, by exploring possible: 1) facilitators, 2) barriers and 3) opportunities to add value for the client during the work disability assessment. For this explorative qualitative study, 7 semi-structured interviews were conducted with MEs in the Netherlands. Thematic coding was performed for all interviews. A large variety of facilitators (n = 22), barriers (n = 17) and opportunities (n = 11) were identified and inductively subdivided into four main themes: 1) coherent process, including all time related aspects, 2) interdisciplinary collaboration, including all aspects related to the collaboration between the ME and other professionals, 3) client-centred interaction, including all aspects related to the supportive interplay from the ME towards the client, and 4) information provision on all aspects during the work disability assessment process towards the client to ensure a valuable work disability assessment process. The overview of identified possible facilitators, barriers and opportunities to add value for clients from the perspective of the ME may stimulate improvement in the current work disability assessment practice and to better match the client needs.