Neuropsychiatric symptoms of cholinergic deficiency occur with degradation of the projections from the nucleus basalis of Meynert

This study aims to evaluate the relation between a cluster of neuropsychiatric symptoms related to cholinergic deficiency and degradation of the cortical cholinergic projections which project from the nucleus basalis of Meynert to the cerebral cortex. An atlas of the pathway from the nucleus basalis to the cortex (NbM cortical pathway) was constructed using diffusion tensor imaging and tractography in 87 memory clinic patients. Structural degradation was considered to be represented by lower fractional anisotropy (FA) and higher mean diffusivity (MD). Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. A predefined cluster including agitation, anxiety, apathy, delusions, hallucinations, and irritability was labeled as the cholinergic deficiency syndrome (CDS). In regression analyses, lower FA and higher MD in the NbM cortical pathway were associated with CDS symptoms but not with other neuropsychiatric symptoms. These associations were independent of cerebral atrophy and overall FA or MD. There was no association between interruption of the NbM cortical pathway by white matter hyperintensities and CDS symptoms. Cox regression suggested a trend for higher mortality with lower FA in the NbM cortical pathway may exist. These findings provide anatomical support for the hypothesis that degradation of the cholinergic projections from the nucleus basalis of Meynert may lead to a distinct clinical syndrome. Future studies could use our results to test the utility of assessing NbM projection integrity to identify patients who may benefit from cholinergic treatment or with a worse prognosi

Postural and gait symptoms in de novo Parkinson's disease patients correlate with cholinergic white matter pathology

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Soft Tissue Sarcoma: The Predominant Primary Malignancy in the Retroperitoneum

Purpose. In the clinical work-up of a retroperitoneal mass, the diagnosis of soft tissue sarcoma is often not considered. Incidence rates of various malignant and benign retroperitoneal tumours were studied to determine the incidence of soft tissue sarcoma in comparison with other neoplasms in the retroperitoneal space

Antihypertensive medication classes and risk of incident dementia in primary care patients: a longitudinal cohort study in the Netherlands

Background: Hypertension is a modifiable risk factor for dementia affecting over 70% of individuals older than 60. Lowering dementia risk through preferential treatment with antihypertensive medication (AHM) classes that are otherwise equivalent in indication could offer a cost-effective, safe, and accessible approach to reducing dementia incidence globally. Certain AHM-classes have been associated with lower dementia risk, potentially attributable to angiotensin-II-receptor (Ang-II) stimulating properties. Previous study results have been inconclusive, possibly due to heterogeneous methodology and limited power. We aimed to comprehensively investigate associations between AHM (sub-)classes and dementia risk using large-scale continuous, real-world prescription and outcome data from primary care. Methods: We used data from three Dutch General Practice Registration Networks. Primary endpoints were clinical diagnosis of incident all-cause dementia and mortality. Using Cox regression analysis with time-dependent covariates, we compared the use of angiotensin-converting enzyme inhibitors (ACEi) to angiotensin receptor blockers (ARBs), beta blockers, calcium channel blockers (CCBs), and diuretics; and Ang-II-stimulating- to Ang-II-inhibiting AHM. Findings: Of 133,355 AHM-using participants, 5877 (4.4%) developed dementia, and 14,079 (10.6%) died during a median follow-up of 7.6 [interquartile range = 4.1–11.0] years. Compared to ACEi, ARBs [HR = 0.86 (95% CI = 0.80–0.92)], beta blockers [HR = 0.81 (95% CI = 0.75–0.87)], CCBs [HR = 0.77 (95% CI = 0.71–0.84)], and diuretics [HR = 0.65 (95% CI = 0.61–0.70)] were associated with significantly lower dementia risks. Regarding competing risk of death, beta blockers [HR = 1.21 (95% CI = 1.15–1.27)] and diuretics [HR = 1.69 (95% CI = 1.60–1.78)] were associated with higher, CCBs with similar, and ARBs with lower [HR = 0.83 (95% CI = 0.80–0.87)] mortality risk. Dementia [HR = 0.88 (95% CI = 0.82–0.95)] and mortality risk [HR = 0.86 (95% CI = 0.82–0.91)] were lower for Ang-II-stimulating versus Ang-II-inhibiting AHM. There were no interactions with sex, diabetes, cardiovascular disease, and number of AHM used. Interpretation: Among patients receiving AHM, ARBs, CCBs, and Ang-II-stimulating AHM were associated with lower dementia risk, without excess mortality explaining these results. Extensive subgroup and sensitivity analyses suggested that confounding by indication did not importantly influence our findings. Dementia risk may be influenced by AHM-classes’ angiotensin-II-receptor stimulating properties. An RCT comparing BP treatment with different AHM classes with dementia as outcome is warranted. Funding: Netherlands Organisation for Health, Research and Development (ZonMw); Stoffels-Hornstra Foundation

Adding ethnicity to cardiovascular risk prediction: External validation and model updating of SCORE2 using data from the HELIUS population cohort

BACKGROUND: Current prediction models for mainland Europe do not include ethnicity, despite ethnic disparities in cardiovascular disease (CVD) risk. SCORE2 performance was evaluated across the largest ethnic groups in the Netherlands and ethnic backgrounds were added to the model. METHODS: 11,614 participants, aged between 40 and 70 years without CVD, from the population-based multi-ethnic HELIUS study were included. Fine and Gray models were used to calculate sub-distribution hazard ratios (SHR) for South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin groups, representing their CVD risk relative to the Dutch group, on top of individual SCORE2 risk predictions. Model performance was evaluated by discrimination, calibration and net reclassification index (NRI). RESULTS: Overall, 274 fatal and non-fatal CVD events, and 146 non-cardiovascular deaths were observed during a median of 7.8 years follow-up (IQR 6.8-8.8). SHRs for CVD events were 1.86 (95 % CI 1.31-2.65) for the South-Asian Surinamese, 1.09 (95 % CI 0.76-1.56) for the African-Surinamese, 1.48 (95 % CI 0.94-2.31) for the Ghanaian, 1.63 (95 % CI 1.09-2.44) for the Turkish, and 0.67 (95 % CI 0.39-1.18) for the Moroccan origin groups. Adding ethnicity to SCORE2 yielded comparable calibration and discrimination [0.764 (95 % CI 0.735-0.792) vs. 0.769 (95 % CI 0.740-0.797)]. The NRI for adding ethnicity to SCORE2 was 0.24 (95 % CI 0.18-0.31) for events and - 0.12 (95 % CI -0.13-0.12) for non-events. CONCLUSIONS: Adding ethnicity to the SCORE2 risk prediction model in a middle-aged, multi-ethnic Dutch population did not improve overall discrimination but improved risk classification, potentially helping to address CVD disparities through timely treatment

Translating Pharmacogenomics: Challenges on the Road to the Clinic

Pharmacogenomics is one of the first clinical applications of the postgenomic era. It promises personalized medicine rather than the established “one size fits all” approach to drugs and dosages. The expected reduction in trial and error should ultimately lead to more efficient and safer drug therapy. In recent years, commercially available pharmacogenomic tests have been approved by the Food and Drug Administration (FDA), but their application in patient care remains very limited. More generally, the implementation of pharmacogenomics in routine clinical practice presents significant challenges. This article presents specific clinical examples of such challenges and discusses how obstacles to implementation of pharmacogenomic testing can be addressed

RELEASE-HF study:a protocol for an observational, registry-based study on the effectiveness of telemedicine in heart failure in the Netherlands

Introduction:Meta-analyses show postive effects of telemedicine in heart failure (HF) management on hospitalisation, mortality and costs. However, these effects are heterogeneous due to variation in the included HF population, the telemedicine components and the quality of the comparator usual care. Still, telemedicine is gaining acceptance in HF management. The current nationwide study aims to identify (1) in which subgroup(s) of patients with HF telemedicine is (cost-)effective and (2) which components of telemedicine are most (cost-) effective. Methods and analysis:The RELEASE-HF ('REsponsible roLl-out of E-heAlth through Systematic Evaluation -Heart Failure') study is a multicentre, observational, registry-based cohort study that plans to enrol 6480 patients with HF using data from the HF registry facilitated by the Netherlands Heart Registration. Collected data include patient characteristics, treatment information and clinical outcomes, and are measured at HF diagnosis and at 6 and 12 months afterwards. The components of telemedicine are described at the hospital level based on closed-ended interviews with clinicians and at the patient level based on additional data extracted from electronic health records and telemedicine-generated data. The costs of telemedicine are calculated using registration data and interviews with clinicians and finance department staff. To overcome missing data, additional national databases will be linked to the HF registry if feasible. Heterogeneity of the effects of offering telemedicine compared with not offering on days alive without unplanned hospitalisations in 1 year is assessed across predefined patient characteristics using exploratory stratified analyses. The effects of telemedicine components are assessed by fitting separate models for component contrasts. Ethics and dissemination:The study has been approved by the Medical Ethics Committee 2021 of the University Medical Center Utrecht (the Netherlands). Results will be published in peer-reviewed journals and presented at (inter)national conferences. Effective telemedicine scenarios will be proposed among hospitals throughout the country and abroad, if applicable and feasible.</p

Doctor–patient communication in a Southeast Asian setting: the conflict between ideal and reality

Doctor–patient communication has been extensively studied in non-Western contexts and in relation to patients’ cultural and education backgrounds. This study explores the perceived ideal communication style for doctor–patient consultations and the reality of actual practice in a Southeast Asian context. We conducted the study in a teaching hospital in Indonesia, using a qualitative and a quantitative design. In-depth interviews were conducted with ten internal medicine specialists, ten internal medicine residents, 16 patients in two groups based on education level and ten most senior medical students. The contributions of doctors and patients to the communication during consultations were observed and rated quantitatively by thirty internal medicine residents, 393 patients with different educational backgrounds and ten senior medical students. The ‘informed and shared decision making’ is the central observation in this quantitative study. The results of the interviews showed that Southeast Asian stakeholders are in favor of a partnership style of communication and revealed barriers to achieving this: doctors and patients are not prepared for a participatory style and high patient load due to an inefficient health care system does not allow sufficient time for this type of communication. The results of the quantitative study showed a sharp contrast between observed and ideal communication styles. A paternalistic style seems to prevail, irrespective of patients’ educational background. We found a sharp conflict between ideal and reality concerning doctor–patient communication in a Southeast Asian context. Further studies should examine ways to change the prevailing communication style in the desired direction

RELEASE-HF study:a protocol for an observational, registry-based study on the effectiveness of telemedicine in heart failure in the Netherlands

Introduction:Meta-analyses show postive effects of telemedicine in heart failure (HF) management on hospitalisation, mortality and costs. However, these effects are heterogeneous due to variation in the included HF population, the telemedicine components and the quality of the comparator usual care. Still, telemedicine is gaining acceptance in HF management. The current nationwide study aims to identify (1) in which subgroup(s) of patients with HF telemedicine is (cost-)effective and (2) which components of telemedicine are most (cost-) effective. Methods and analysis:The RELEASE-HF ('REsponsible roLl-out of E-heAlth through Systematic Evaluation -Heart Failure') study is a multicentre, observational, registry-based cohort study that plans to enrol 6480 patients with HF using data from the HF registry facilitated by the Netherlands Heart Registration. Collected data include patient characteristics, treatment information and clinical outcomes, and are measured at HF diagnosis and at 6 and 12 months afterwards. The components of telemedicine are described at the hospital level based on closed-ended interviews with clinicians and at the patient level based on additional data extracted from electronic health records and telemedicine-generated data. The costs of telemedicine are calculated using registration data and interviews with clinicians and finance department staff. To overcome missing data, additional national databases will be linked to the HF registry if feasible. Heterogeneity of the effects of offering telemedicine compared with not offering on days alive without unplanned hospitalisations in 1 year is assessed across predefined patient characteristics using exploratory stratified analyses. The effects of telemedicine components are assessed by fitting separate models for component contrasts. Ethics and dissemination:The study has been approved by the Medical Ethics Committee 2021 of the University Medical Center Utrecht (the Netherlands). Results will be published in peer-reviewed journals and presented at (inter)national conferences. Effective telemedicine scenarios will be proposed among hospitals throughout the country and abroad, if applicable and feasible.</p