CT evaluation of bowel wall enhancement in pneumatosis intestinalis: preventing non-therapeutic laparotomies.

PURPOSE: To evaluate the diagnostic performance of bowel wall enhancement for diagnosing concomitant bowel ischemia in patients with parietal pneumatosis (PI) diagnosed at abdominal CT. MATERIALS AND METHODS: From January 1, 2012 to December 31, 2021, 226 consecutive patients who presented with PI on abdominal CT from any bowel segment were included. Variables at the time of the CT were retrospectively extracted from medical charts. CT examinations were blindly analyzed by two independent radiologists. The third reader classified all disagreement of bowel enhancement in three categories: (1) normal bowel enhancement; (2) doubtful bowel wall enhancement; (3) absent bowel wall enhancement. Multivariable logistic regression analysis was performed. Concomitant bowel ischemia was defined as requirement of bowel resection specifically due to ischemic lesion in operated patients and death from bowel ischemia in non-operated patients. RESULTS: Overall, 78/226 (35%) patients had PI associated with concomitant bowel ischemia. At multivariate analysis, Only absence or doubtful bowel wall enhancement was associated with concomitant bowel ischemia (OR = 167.73 95%CI [23.39-4349.81], P < 0,001) and acute mesenteric ischemia associated with PP (OR = 67.94; 95%CI [5.18-3262.36], P < 0.009). Among the 82 patients who underwent a laparotomy for suspected bowel ischemia, rate of non-therapeutic laparotomy increased from 15/59 (25%), 2/6 (50%) and 16/17 (94%) when bowel wall enhancement was absent, doubtful and normal respectively. CONCLUSION: Absence of enhancement of the bowel wall is the primary feature associated with concomitant bowel ischemia. It should be carefully assessed when PI is detected to avoid non-therapeutic laparotomy.

Temporal trends in antibiotic prescribing and serious and nonserious infections in children presenting to general practice: a registry-based longitudinal cohort study of 162 507 individuals.

BACKGROUND: It is crucial to understand the trends in paediatric antibiotic prescribing and serious and nonserious infections to improve antibiotic prescribing practices for children in ambulatory care. OBJECTIVES: Assessing trends in paediatric antibiotic prescribing and infection incidence in general practice from 2002 to 2022. METHODS: In this retrospective cohort study using INTEGO network data from 162 507 patients in Flanders (Belgium), we calculated antibiotic prescribing rates and proportions alongside incidence rates of serious and nonserious infections, stratified by age (0-1, 2-6, 7-12 years) and municipality. We performed autoregressive moving average time-series analyses and seasonality analyses. RESULTS: From 2002 to 2022, antibiotic prescribing rate decreased significantly: 584/1000 person-years (PY) (95% CI 571-597) to 484/1000PY (95% CI 478-491); so did antibiotic overall prescribing proportion: 46.3% (95% CI 45.1-47.6) to 23.3% (95% CI 22.9-23.7) (59.3% amoxicillin and 17.8% broad spectrum). Prescribing proportions dropped significantly for nonserious (45.6% to 20.9%) and increased for serious infections (64.1% to 69.8%). Proportions significantly dropped for acute suppurative otitis media (74.7% to 64.1%), upper respiratory tract infections (44.9% to 16.6%), bronchitis/bronchiolitis (73.6% to 44.1%) and acute tonsillopharyngitis (59.5% to 21.7%), while significantly increasing for pneumonia (65.2% to 80.2%). Nonserious and serious infection incidence rates increased from 785/1000PY and 34.2/1000PY to 1223/1000PY and 64.1/1000PY, respectively. Blood and CRP testing proportions increased significantly. CONCLUSIONS: Antibiotic prescribing in general practice for children declined from 2002 to 2022. Further targeted antibiotic stewardship initiatives are needed to reduce the use of broad-spectrum antibiotics and antibiotic prescribing for conditions such as otitis media and bronchitis/bronchiolitis.

Chemoproteomic discovery of a covalent allosteric inhibitor of WRN helicase.

WRN helicase is a promising target for treatment of cancers with microsatellite instability (MSI) due to its essential role in resolving deleterious non-canonical DNA structures that accumulate in cells with faulty mismatch repair mechanisms1-5. Currently there are no approved drugs directly targeting human DNA or RNA helicases, in part owing to the challenging nature of developing potent and selective compounds to this class of proteins. Here we describe the chemoproteomics-enabled discovery of a clinical-stage, covalent allosteric inhibitor of WRN, VVD-133214. This compound selectively engages a cysteine (C727) located in a region of the helicase domain subject to interdomain movement during DNA unwinding. VVD-133214 binds WRN protein cooperatively with nucleotide and stabilizes compact conformations lacking the dynamic flexibility necessary for proper helicase function, resulting in widespread double-stranded DNA breaks, nuclear swelling and cell death in MSI-high (MSI-H), but not in microsatellite-stable, cells. The compound was well tolerated in mice and led to robust tumour regression in multiple MSI-H colorectal cancer cell lines and patient-derived xenograft models. Our work shows an allosteric approach for inhibition of WRN function that circumvents competition from an endogenous ATP cofactor in cancer cells, and designates VVD-133214 as a promising drug candidate for patients with MSI-H cancers.

Proteomic Ligandability Maps of Spirocycle Acrylamide Stereoprobes Identify Covalent ERCC3 Degraders.

Covalent chemistry coupled with activity-based protein profiling (ABPP) offers a versatile way to discover ligands for proteins in native biological systems. Here, we describe a set of stereo- and regiochemically defined spirocycle acrylamides and the analysis of these electrophilic "stereoprobes" in human cancer cells by cysteine-directed ABPP. Despite showing attenuated reactivity compared to structurally related azetidine acrylamide stereoprobes, the spirocycle acrylamides preferentially liganded specific cysteines on diverse protein classes. One compound termed ZL-12A promoted the degradation of the TFIIH helicase ERCC3. Interestingly, ZL-12A reacts with the same cysteine (C342) in ERCC3 as the natural product triptolide, which did not lead to ERCC3 degradation but instead causes collateral loss of RNA polymerases. ZL-12A and triptolide cross-antagonized one another's protein degradation profiles. Finally, we provide evidence that the antihypertension drug spironolactone─previously found to promote ERCC3 degradation through an enigmatic mechanism─also reacts with ERCC3_C342. Our findings thus describe monofunctional degraders of ERCC3 and highlight how covalent ligands targeting the same cysteine can produce strikingly different functional outcomes.

Integrated Care Models for Older Adults with Depression and Physical Comorbidity: A Scoping Review.

Objective: Multimorbidity is a growing challenge in the care for older people with mental illness. To address both physical and mental illnesses, integrated care management is required. The purpose of this scoping review is to identify core components of integrated care models for older adults with depression and physical comorbidity, and map reported outcomes and implementation strategies. Methods: PubMed, EMBASE, CINAHL and Cochrane Library were searched independently by two reviewers for studies concerning integrated care interventions for older adults with depression and physical comorbidity. We used the SELFIE framework to map core components of integrated care models. Clinical and organisational outcomes were mapped. Results: Thirty-eight studies describing thirteen care models were included. In all care models, a multidisciplinary team was involved. The following core components were mainly described: continuity, person-centredness, tailored holistic assessment, pro-activeness, treatment interaction, individualized care planning, and coordination tailored to complexity of care needs. Twenty-seven different outcomes were evaluated, with more attention given to clinical than to organisational outcomes. Conclusion: The core components that comprise integrated care models are diverse. Future studies should focus more on implementation aspects of the intervention and describe financial parts, e.g., the cost of the intervention for the healthcare user, more transparently.

Assessing mental health from registry data: What is the best proxy?

OBJECTIVE: Medical registries frequently underestimate the prevalence of health problems compared with surveys. This study aimed to determine the registry variables that can serve as a proxy for variables studied in a mental health survey. MATERIALS AND METHODS: Prevalences of depressive symptoms, anxiety and psychoactive medication use from the 2018 Belgian Health Interview Survey (HIS) were compared with same-year prevalences from INTEGO, a Belgian primary care registry. Participants aged 15 and above were included. We assessed correlation using Spearman's rho (SR), and agreement using the intraclass correlation coefficient (ICC). We also calculated the limits of agreement (LOAs) for each comparison. HIS questions about depressive symptoms, anxiety and psychoactive medication use were compared with the following variables from INTEGO: symptom codes, diagnosis codes, free text, antidepressant/benzodiazepine prescriptions and the combinations symptom + diagnosis codes and symptom + diagnosis codes + free text, wherever relevant. RESULTS AND DISCUSSION: Correlation between the HIS and INTEGO was generally high, except for anxiety. Agreement ranged from fair to poor, but increased when combining certain variables, by including free text, or by increasing the prescription frequency to resemble chronic use. Agreement remained poor when comparing questions about anxiety. Prevalences from INTEGO were mostly underestimates. CONCLUSION: The external validity of medical registries can be poor, especially compared with survey data. A considerate choice of variables and prescription chronicity is needed to accurately use a registry as a surveillance tool for mental health.

Quantifying iodine concentration in the normal bowel wall using dual-energy CT: influence of patient and contrast characteristics.

This study aimed to establish quantitative references of the normal bowel wall iodine concentration (BWIC) using dual energy CT (DECT). This single-center retrospective study included 248 patients with no history of gastrointestinal disease who underwent abdominal contrast-enhanced DECT between January and April 2022. The BWIC was normalized by the iodine concentration of upper abdominal organs (BWICorgan,) and the iodine concentration (IC) of the aorta (BWICaorta). BWIC decreased from the stomach to the rectum (mean 2.16 ± 0.63 vs. 2.19 ± 0.63 vs. 2.1 ± 0.58 vs. 1.67 ± 0.47 vs. 1.31 ± 0.4 vs. 1.18 ± 0.34 vs. 0.94 ± 0.26 mgI/mL for the stomach, duodenum, jejunum, ileum, right colon, left colon and rectum, respectively; P < 0.001). By multivariate analysis, BWIC was associated with a higher BMI (OR:1.01, 95% CI 1.00-1.02, P < 0.001) and with a higher injected contrast dose (OR: 1.51; 95% CI 1.36-1.66, P < 0.001 and 2.06; 95% CI 1.88-2.26, P < 0.001 for 500 mgI/kg and 600 mgI/kg doses taking 400 mgI/kg dose as reference). The BWICorgan was shown independent from patients and contrast-related variables while the BWICaorta was not. BWIC varies according to bowel segments and is dependent on the total iodine dose injected. It shall be normalized with the IC of the upper abdominal organs.

Assigning functionality to cysteines by base editing of cancer dependency genes.

Covalent chemistry represents an attractive strategy for expanding the ligandability of the proteome, and chemical proteomics has revealed numerous electrophile-reactive cysteines on diverse human proteins. Determining which of these covalent binding events affect protein function, however, remains challenging. Here we describe a base-editing strategy to infer the functionality of cysteines by quantifying the impact of their missense mutation on cancer cell proliferation. The resulting atlas, which covers more than 13,800 cysteines on more than 1,750 cancer dependency proteins, confirms the essentiality of cysteines targeted by covalent drugs and, when integrated with chemical proteomic data, identifies essential, ligandable cysteines in more than 160 cancer dependency proteins. We further show that a stereoselective and site-specific ligand targeting an essential cysteine in TOE1 inhibits the nuclease activity of this protein through an apparent allosteric mechanism. Our findings thus describe a versatile method and valuable resource to prioritize the pursuit of small-molecule probes with high function-perturbing potential.

Short-term mortality prediction using a combination of clinical and CT features: Refining the prognosis of critically ill patients in shock.

PURPOSE: To assess the predictive value of combining CT and clinical findings for predicting 10-day mortality in critically ill patients in shock. MATERIALS AND METHODS: From January 1, 2018, to December 31, 2021, 289 consecutives critically ill patients in shock who underwent a contrast enhanced CT were included. Variables at the time of the CT were retrospectively extracted from medical charts. CT examinations were blindly analyzed by two independent radiologists. Multivariable analysis was performed, combining clinical and CT features. A simple survival score for 10-day mortality prediction was built and validated in a further independent external cohort of 70 patients. RESULTS: 10-day mortality rate was 135/289 (47%) in the study sample. At multivariate analysis, catecholamine infusion (OR = 2.11; 95%CI [1.21-4.18], P = 0.011), lactates level > 5 mmol/l (OR = 3.54; 95%CI [1.94-6.54], P < 0.001); total bilirubin > 50 mg/l (OR = 1.79 CI 95% [1.03-3.13], P = 0.039); small bowel dilation (OR = 1.82; 95%CI [1.01-3.32], P = 0.047); diffuse kidney infarction (OR = 2.76; 95%CI [1.26-6.37], P = 0.013) and superior mesentery artery < 5 mm (OR = 1.96; 95%CI [1.10-3.49], P = 0.021) were associated with 10-days mortality. The AUC of the combined model was 0.79; 95%CI [0.74-0.85] in the study sample and 0.87; 95%CI [0.71-0.91] in the validation cohort. CONCLUSION: The combination of CT imaging features and clinical data should emerge as a novel approach to predict short-term mortality in critically ill patients in shock.

Health risk assessment of potentially toxic elements (PTEs) concentrations in soil and fruits of selected perennial economic trees growing naturally in the vicinity of the abandoned mining ponds in Kuba, Bokkos Local Government Area (LGA) Plateau State, Nigeria.

This study was designed to determine the level of potentially toxic elements (PTEs) contamination in soil and selected fruits and assesses the health risk of inhabitants in the abandoned tin mining community in Kuba, Bokkos LGA. Samples of the abandoned mine soil and selected fruits mango (Magnifera indica), guava (Psidium guajava), avocado pear (Persea americana), and banana (Musa spp)) from the vicinity of the abandoned mine were analyzed for the presence of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) using inductively coupled plasma mass spectrometry (ICP-MS). The results showed that the levels of all the PTEs analysed in the abandoned mine soil samples were significantly (p < 0.05) higher than their corresponding values in the control soil from the non-mining area. Except for Cd, the mean concentrations of As, Cr, Cu, Mn, Ni, and Pb were significantly higher than the FAO/WHO maximum permissible limit. Except for Zn in guava fruits and Cd in avocado fruits, the mean concentration of PTEs in fruits from abandoned mines was significantly (p < 0.05) higher than their corresponding control values. In contrast, the mean levels of As, Cr, Cu, Mn, Ni, and Pb in the investigated fruits were significantly (p < 0.05) higher than FAO/WHO maximum permissible limits established for fruits. The studied fruits remarkably took up and bioaccumulated PTEs from the abandoned mine soil. Mango fruit significantly bioaccumulated As (5.40), Cd (3.40), and Zn (2.81). Guava fruit bioaccumulated As (1.50) and Cd (4.60), while avocado bioaccumulated As (3.53), Cd (3.80), and Zn (6.48). Banana bioaccumulated As (0.96), Cd (0.80), and Zn (6.78). The hazard quotient values for PTEs investigated in fruits for adults, and children were several folds greater than 1. The hazard index (HI) for the PTEs through consuming fruits for children and adults was greater than 1, indicating that possible health risks exist for both local children and adults. However, the HI values for the children were higher than those for adults, implying that children were exposed to more potential noncarcinogenic health risks from PTEs than adults. The total cancer risk (TCR) values for Cr and Ni for all the fruits studied were within 10-3-10-1, which is several-fold higher than the permissible limits (10-6 and < 10-4), indicating high carcinogenic risk. TCR values for Cd and Pb in all the fruits, except for Cd in guava and avocado fruits for children, were within the range of 10-5-10-4, indicating that they are associated with moderate risk. The CR values for all the PTEs in all the fruits for adults and children except for mango fruit adults were within 10-2-10-1, indicating high carcinogenic risk. In conclusion, the results and risk assessment provided by this study indicate that human exposure to fruits from abandoned mines suggests a high vulnerability of the local community to PTE toxicity. Long-term preventive measures to safeguard the health of the residents need to be put in place.

Trends in the registration of anxiety in Belgian primary care from 2000 to 2021: a registry-based study.

BACKGROUND: Anxiety is frequently encountered in general practice, but figures regarding prevalence and incidence in this healthcare setting remain scarce. AIM: To provide insight about the trends in prevalence and incidence of anxiety in Belgian general practice, as well as the comorbidities and treatment of anxiety in this context. DESIGN AND SETTING: Retrospective cohort study using the INTEGO morbidity registration network, with clinical data from over 600 000 patients in Flanders, Belgium. METHOD: Trends in age-standardised prevalence and incidence of anxiety from 2000 to 2021 as well as prescriptions in patients with prevalent anxiety were analysed with joinpoint regression. Comorbidity profiles were analysed using the Cochran-Armitage test and the Jonckheere-Terpstra test. RESULTS: During the 22-year study period, 8451 unique patients with anxiety were identified. The prevalence of anxiety diagnoses rose significantly during this period, from 1.1% in 2000 to 4.8% in 2021. The overall incidence rate rose from 1.1/1000 patient-years (PY) in 2000 to 9.9/1000 PY in 2021. The average chronic disease count per patient increased significantly during the study period, from 1.5 to 2.3 chronic conditions. The most frequent comorbidities in patients with anxiety in 2017-2021 were malignancy (20.1%), hypertension (18.2%), and irritable bowel syndrome (13.5%). The proportion of patients treated with psychoactive medication rose from 25.7% to almost 40% over the study period. CONCLUSION: A significantly increasing prevalence and incidence of physician-registered anxiety was found in the study. Patients with anxiety tend to become more complex, with more comorbidities. Treatment for anxiety in Belgian primary care is very dependent on medication.

Proteomic discovery of chemical probes that perturb protein complexes in human cells.

Most human proteins lack chemical probes, and several large-scale and generalizable small-molecule binding assays have been introduced to address this problem. How compounds discovered in such "binding-first" assays affect protein function, nonetheless, often remains unclear. Here, we describe a "function-first" proteomic strategy that uses size exclusion chromatography (SEC) to assess the global impact of electrophilic compounds on protein complexes in human cells. Integrating the SEC data with cysteine-directed activity-based protein profiling identifies changes in protein-protein interactions that are caused by site-specific liganding events, including the stereoselective engagement of cysteines in PSME1 and SF3B1 that disrupt the PA28 proteasome regulatory complex and stabilize a dynamic state of the spliceosome, respectively. Our findings thus show how multidimensional proteomic analysis of focused libraries of electrophilic compounds can expedite the discovery of chemical probes with site-specific functional effects on protein complexes in human cells.

Personality traits and mental distress after COVID-19 testing. Prospective long-term analysis in a Viennese cohort.

Background: Symptoms of mental stress are a hallmark of the COVID-19 pandemic. We hypothesized that just testing for COVID-19 could act as an effective stressor for persisting symptoms of mental distress including posttraumatic stress disorder. Our study aimed to determine whether personal beliefs on individual control and competence (locus of control, LoC) correlate with symptoms of mental distress and positive screening for post-traumatic stress disorder during a 9-month observational period. Methods: Between March and December 2021, we applied online versions of the Questionnaire on Competence and Control Expectations (FKK), the Depression, Anxiety, and Stress Score (DASS), the Short Screening Scale for DSM-IV Posttraumatic Stress Disorder (PTSD), and a medical history questionnaire for COVID-19 symptoms (visit 1). 48 hours after negative COVID-19 testing, DASS was repeated to address relief effects on mental distress (visit 2). Following 90 days (visit 3), development of mental distress was addressed by a combination of DASS and PTSD, while the possible long-term manifestation of PTSD was evaluated 9 months later (visit 4). Results: At visit 1, 7.4 percent of the total sample (n = 867) demonstrated a positive screening for PTSD, while after nine months (at visit 4), 8.9 percent of the remaining sample (n = 204) had positive screening results. The mean age was 36.2 years; 60.8% were women, 39.2% men. In contrast to individuals with negative PTSD screening, these participants demonstrated a significantly different LoC personality profile. This was confirmed by the results of both DASS and the COVID-19 medical history questionnaire. Conclusion: Following testing for COVID-19, individuals with positive long-term PTSD screening present with significantly different personality traits than those w/o suggesting that self-confidence and effective control over one's own actions serve as a protective function against mental distress.

The Impact of the COVID-19 Pandemic on the Registration and Care Provision of Mental Health Problems in General Practice: Registry-Based Study.

BACKGROUND: The impact of the COVID-19 pandemic on mental health in general practice remains uncertain. Several studies showed an increase in terms of mental health problems during the pandemic. In Belgium, especially during the first waves of the pandemic, access to general practice was limited. Specifically, it is unclear how this impacted not only the registration of mental health problems itself but also the care for patients with an existing mental health problem. OBJECTIVE: This study aimed to know the impact of the COVID-19 pandemic on (1) the incidence of newly registered mental health problems and (2) the provision of care for patients with mental health problems in general practice, both using a pre-COVID-19 baseline. METHODS: The prepandemic volume of provided care (care provision) for patients with mental health problems was compared to that from 2020-2021 by using INTEGO, a Belgian general practice morbidity registry. Care provision was defined as the total number of new registrations in a patient's electronic medical record. Regression models evaluated the association of demographic factors and care provision in patients with mental health problems, both before and during the pandemic. RESULTS: During the COVID-19 pandemic as compared to before the COVID-19 pandemic, the incidence of registered mental health problems showed a fluctuating course, with a sharp drop in registrations during the first wave. Registrations for depression and anxiety increased, whereas the incidence of registered eating disorders, substance abuse, and personality problems decreased. During the 5 COVID-19 waves, the overall incidence of registered mental health problems dropped during the wave and rose again when measures were relaxed. A relative rise of 8.7% and 40% in volume of provided care, specifically for patients with mental health problems, was seen during the first and second years of the COVID-19 pandemic, respectively. Care provision for patients with mental health problems was higher in older patients, male patients, patients living in center cities (centrumsteden), patients with lower socioeconomic status (SES), native Belgian patients, and patients with acute rather than chronic mental health problems. Compared to prepandemic care provision, a reduction of 10% was observed in people with a low SES. CONCLUSIONS: This study showed (1) a relative overall increase in the registrations of mental health problems in general practice and (2) an increase in care provision for patients with mental health problems in the first 2 years of the COVID-19 pandemic. Low SES remained a determining factor for more care provision, but care provision dropped significantly in people with mental health problems with a low SES. Our findings suggest that the pandemic in Belgium was also largely a "syndemic," affecting different layers of the population disproportionately.

NLRP3 activation contributes to endothelin-1-induced erectile dysfunction.

In the present study, we hypothesized that endothelin (ET) receptors (ETA and ETB ) stimulation, through increased calcium and ROS formation, leads to Nucleotide Oligomerization Domain-Like Receptor Family, Pyrin Domain Containing 3 (NLRP3) activation. Intracavernosal pressure (ICP/MAP) was measured in C57BL/6 (WT) mice. Functional and immunoblotting assays were performed in corpora cavernosa (CC) strips from WT, NLRP3-/- and caspase-/- mice in the presence of ET-1 (100 nM) and vehicle, MCC950, tiron, BAPTA AM, BQ123, or BQ788. ET-1 reduced the ICP/MAP in WT mice, and MCC950 prevented the ET-1 effect. ET-1 decreased CC ACh-, sodium nitroprusside (SNP)-induced relaxation, and increased caspase-1 expression. BQ123 an ETA receptor antagonist reversed the effect. The ETB receptor antagonist BQ788 also reversed ET-1 inhibition of ACh and SNP relaxation. Additionally, tiron, BAPTA AM, and NLRP3 genetic deletion prevented the ET-1-induced loss of ACh and SNP relaxation. Moreover, BQ123 diminished CC caspase-1 expression, while BQ788 increased caspase-1 and IL-1ß levels in a concentration-dependent manner (100 nM-10 µM). Furthermore, tiron and BAPTA AM prevented ET-1-induced increase in caspase-1. In addition, BAPTA AM blocked ET-1-induced ROS generation. In conclusion, ET-1-induced erectile dysfunction depends on ETA - and ETB -mediated activation of NLRP3 in mouse CC via Ca2+ -dependent ROS generation.

Trends in prevalence and incidence of registered dementia and trends in multimorbidity among patients with dementia in general practice in Flanders, Belgium, 2000-2021: a registry-based, retrospective, longitudinal cohort study.

OBJECTIVES: With the ageing of our population, it seems plausible that the prevalence of both dementia and multimorbidity will increase in the following decades. The aim of this study is to examine the trends in prevalence and incidence of registered dementia and trends in multimorbidity in patients with dementia in general practice in Flanders. DESIGN: Retrospective, longitudinal cohort study. SETTING: Primary care practices across Flanders, Belgium. PARTICIPANTS: Patients included in the Intego database. METHODS: Data were collected from the Intego database, a Belgian general practice registration network, from 1 January 2000 to 31 December 2021. Joinpoint regression, the Cochran-Armitage test and Jonckheere-Terpstra test were used for the trend analysis. RESULTS: Data from 149 492 unique patients aged 65 years and older were available. From 2000 to 2021, 3835 incident cases of dementia were found. The age-adjusted prevalence of registered dementia significantly increased during this study period, from 1.19% to 2.43% (average annual percentage change (AAPC) 3.3; 95% CI 2.7 to 4.0). Incidence increased from 3.68 to 5.86 per 1000 patient years overall (AAPC 1.8, 95% CI -2.0 to 5.7), but declined in recent years (annual percentage change -8.1, 95% CI -14.8 to -0.8). Almost three-quarters of the patients with dementia (74.8%) suffered from multimorbidity (three or more comorbidities) and this increased significantly during the study period (p=0.0031). By 2021, 86.7% and 74.8% of the patients with dementia suffered from two or more or three or more chronic conditions, respectively. Hypertension (47.9%), osteoarthritis (29.7%) and lipid metabolism disorders (25.7%) were the most prevalent conditions. CONCLUSIONS: The prevalence of registered dementia doubled over a 22-year time period, mirroring the increasing health burden by this disease globally. Furthermore, three-quarters of the patients with dementia suffered from multimorbidity, underlining the urgent need to implement comorbidity management and patient-centred care in dementia.