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Background: Sudden cardiac death is responsible for 10% to 20% of all deaths in Europe. The current study investigates how well the risk of sudden cardiac death can be predicted. To this end, we validated a previously developed prediction model for sudden cardiac death from the Atherosclerosis Risk in Communities study (USA). Methods: Data from participants of the Copenhagen City Heart Study (CCHS) (n=9988) was used to externally validate the previously developed prediction model for sudden cardiac death. The model's performance was assessed through discrimination (C-statistic) and calibration by the Hosmer-Lemeshow goodness-of-fit (HL) statistics suited for censored data and visual inspection of calibration plots. Additional validation was performed using data from the Hoorn Study (N=2045), employing the same methods. Results: During ten years of follow-up of CCHS participants (mean age: 58.7 years, 56.2% women), 425 experienced SCD (4.2%). The prediction model showed good discrimination for sudden cardiac death risk (C-statistic: 0.81, 95% CI: 0.79-0.83). Calibration was robust (HL statistic: P=0.8). Visual inspection of the calibration plot showed that the calibration could be improved. Sensitivity was 89.8%, and specificity was 60.6%. The positive and negative predictive values were 10.1% and 99.2%. Model performance was similar in the Hoorn Study (C-statistic: 0.81, 95% CI: 0.77-0.85 and the HL statistic: 1.00). Conclusion: Our study showed that the previously developed prediction model in North American adults performs equally well in identifying those at risk for sudden cardiac death in a general North-West European population. However, the positive predictive value is low.

Background: Clinically feasible and reliable methods to measure motor control in people with low back pain (LBP) are lacking. This reliability and measurement error study design (i.e. repeated measurements in stable patients) aimed to determine the intra- and interrater reliability, and measurement errors of several parameters for two clinical lumbar motor control tests. Method: Participants 18–65 years of age, with current or a history of LBP performed a spiral tracking task (n = 33; i.e., tracing a spiral on a computer monitor by making spinal movements) or a repositioning task (n = 34; i.e., returning the trunk to a predefined position). Accelerometers were used to measure trunk positions. To explore the potential of these tests, we evaluated a broad range of parameters. To assess intra- and interrater reliability, we calculated the intraclass correlation coefficient (ICC (2,1) for absolute agreement), standard error of measurement and smallest detectable change for each parameter. Findings: Overall, the interrater reliability of the spiral tracking test was good (ICC>0.75). The reliability of the second and third trial revealed higher ICC values compared to the reliability of the first two trials. The intra- and interrater reliability of the repositioning test was overall poor (ICC

Purpose Many studies report about risk factors associated with adverse changes in mental health during the COVID-19 pandemic while few studies report about protective and buffering factors, especially in older adults. We present an observational study to assess protective and buffering factors against COVID-19 related adverse mental health changes in older adults. Methods 899 older adults (55 +) in the Netherlands were followed from 2018/19 to two pandemic time points (June–October 2020 and March–August 2021). Questionnaires included exposure to pandemic-related adversities (“COVID-19 exposure”), depressive and anxiety symptoms, loneliness, and pre-pandemic functioning. Linear regression analyses estimated main effects of COVID-19 exposure and protective factors on mental health changes; interaction effects were tested to identify buffering factors. Results Compared to pre-pandemic, anxiety symptoms, depression symptoms and loneliness increased. A higher score on the COVID-19 adversity index was associated with stronger negative mental health changes. Main effects: internet use and high mastery decreased depressive symptoms; a larger network decreased anxiety symptoms; female gender, larger network size and praying decreased loneliness. COVID-19 vaccination buffered against COVID-19 exposure-induced anxiety and loneliness, a partner buffered against COVID-19 exposure induced loneliness. Conclusion Exposure to COVID-19 adversity had a cumulative negative impact on mental health. Improving coping, finding meaning, stimulating existing religious and spiritual resources, network interventions and stimulating internet use may enable older adults to maintain mental health during events with large societal impact, yet these factors appear protective regardless of exposure to specific adversities. COVID-19 vaccination had a positive effect on mental health.

Purpose Tau pathology is associated with concurrent atrophy and decreased cerebral blood flow (CBF) in Alzheimer’s disease (AD), but less is known about their temporal relationships. Our aim was therefore to investigate the association of concurrent and longitudinal tau PET with longitudinal changes in atrophy and relative CBF. Methods We included 61 individuals from the Amsterdam Dementia Cohort (mean age 65.1 ± 7.5 years, 44% female, 57% amyloid-β positive [Aβ +], 26 cognitively impaired [CI]) who underwent dynamic [18F]flortaucipir PET and structural MRI at baseline and 25 ± 5 months follow-up. In addition, we included 86 individuals (68 CI) who only underwent baseline dynamic [18F]flortaucipir PET and MRI scans to increase power in our statistical models. We obtained [18F]flortaucipir PET binding potential (BPND) and R1 values reflecting tau load and relative CBF, respectively, and computed cortical thickness from the structural MRI scans using FreeSurfer. We assessed the regional associations between i) baseline and ii) annual change in tau PET BPND in Braak I, III/IV, and V/VI regions and cortical thickness or R1 in cortical gray matter regions (spanning the whole brain) over time using linear mixed models with random intercepts adjusted for age, sex, time between baseline and follow-up assessments, and baseline BPND in case of analyses with annual change as determinant. All analyses were performed in Aβ− cognitively normal (CN) individuals and Aβ+ (CN and CI) individuals separately. Results In Aβ+ individuals, greater baseline Braak III/IV and V/VI tau PET binding was associated with faster cortical thinning in primarily frontotemporal regions. Annual changes in tau PET were not associated with cortical thinning over time in either Aβ+ or Aβ− individuals. Baseline tau PET was not associated with longitudinal changes in relative CBF, but increases in Braak III/IV tau PET over time were associated with increases in parietal relative CBF over time in Aβ + individuals. Conclusion We showed that higher tau load was related to accelerated cortical thinning, but not to decreases in relative CBF. Moreover, tau PET load at baseline was a stronger predictor of cortical thinning than change of tau PET signal.

Purpose: To investigate the agreement between an online nurse-assisted eye-screening tool and reference tests in older adults receiving home healthcare and to collect user experiences. Methods: Older adults (65+) receiving home healthcare were included. Home healthcare nurses assisted in administering the eye-screening tool at participants' homes. Approximately 2 weeks later, a researcher administered reference tests at participants' homes. Experiences from participants and home healthcare nurses were collected. Agreement in outcomes (distance and near visual acuity, with the latter being measured using two different optotypes, and macular problems) between the eye-screening tool and reference clinical testing was compared. A difference of less than ±0.15 logMAR was considered acceptable. Results: A total of 40 participants were included. Here, we describe the results for the right eye; results for the left eye were similar. The mean difference between the eye-screening tool and reference tests for distance visual acuity was 0.02 logMAR. The mean difference between the eye-screening tool and reference tests using two different optotypes for near visual acuity was 0.06 and 0.03 logMAR, respectively. The majority of the individual data points were within the ±0.15 logMAR threshold (75%, 51% and 58%, respectively). The agreement between tests for macular problems was 75%. Participants and home healthcare nurses were generally satisfied with the eye-screening tool, although remarks for further improvements were made. Conclusions: The eye-screening tool is promising for nurse-assisted eye screening in older adults receiving home healthcare, with the mostly satisfactory agreement. After implementing the eye-screening tool in practice, cost-effectiveness needs to be investigated.

Objective: Low dietary guideline adherence is persistent, but there is limited understanding of how individuals with varying socio-economic backgrounds reach a certain dietary intake. We investigated how quantitative and qualitative data on dietary guidelines adherence correspond and complement each other, to what extent determinants of guideline adherence in quantitative data reflect findings on determinants derived from qualitative data and which of these determinants emerged as interdependent in the qualitative data. Design: This mixed-methods study used quantitative questionnaire data (n 1492) and qualitative data collected via semi-structured telephone interviews (n 24). Quantitative data on determinants and their association with total guideline adherence (scored 0–150) were assessed through linear regression. Directed content analysis was used for qualitative data. Setting: Dutch urban areas. Participants: Adults aged 18–65 years. Results: A range of determinants emerged from both data sources, for example higher levels of cognitive restraint (β 5·6, 95 % CI 4·2, 7·1), habit strength of vegetables (β 4·0, 95 % CI 3·3, 4·7) and cooking skills (β 4·7, 95 % CI 3·5, 5·9), were associated with higher adherence. Qualitative data additionally suggested the influence of food prices, strong dietary habits and the social aspect of eating, and for the determinants cognitive restraint, habit strength related to vegetables, food prices and home cooking, some variation between interviewees with varying socio-economic backgrounds emerged in how these determinants affected guideline adherence. Conclusions: This mixed-methods exploration provides a richer understanding of why adults with varying socio-economic backgrounds do or do not adhere to dietary guidelines. Results can guide future interventions promoting healthy diets across populations.

Purpose The added value of measuring patient-reported outcomes (PROs) for delivering patient-centered care and assessment of healthcare quality is increasingly evident. However, healthcare system wide data collection initiatives are hampered by the proliferation of patient-reported outcome measures (PROMs) and conflicting data collection standards. As part of a national initiative of the Dutch Ministry of Health, Welfare and Sport we developed a consensus-based standard set of generic PROs and PROMs to be implemented across Dutch medical specialist care. Methods A working group of mandated representatives of umbrella organizations involved in Dutch medical specialist care, together with PROM experts and patient organizations worked through a structured, consensus-driven co-creation process. This included literature reviews, online expert and working group meetings, and feedback from national patient- and umbrella organizations. The ‘PROM-cycle’ methodology was used to select feasible, valid, and reliable PROMs to obtain domain scores for each of the PROs included in the set. Results Eight PROs across different domains of health were ultimately endorsed: symptoms (pain & fatigue), functioning (physical, social/participation, mental [anxiety & depression]), and overarching (quality of life & perceived overall health). A limited number of generic PROMs was endorsed. PROMIS short forms were selected as the preferred instruments for all PROs. Several recommendations were formulated to facilitate healthcare system level adoption and implementation of the standard set. Conclusions We developed a consensus-based standard set of Generic PROMs and a set of recommendations to facilitate healthcare system wide implementation across Dutch medical specialist care.

Introduction: Conflicting evidence exists concerning whether having sarcopenic obesity has additive mortality risk over having only sarcopenia or obesity. We examined the independent and combined associations of obesity and probable sarcopenia with all-cause mortality. Methods: The pooled analysis included three large, harmonized datasets (Health 2000 Survey; Health, Aging and Body Composition Study; Longitudinal Aging Study Amsterdam) with mortality follow-up data on individuals aged 70 years and over at baseline (n = 4,612). Obesity indicators included body mass index and waist circumference, and probable sarcopenia was defined based on grip strength. The mixed effects Cox model was used for statistical analyses, adjusting for age, sex, marital status, education, race, physical activity, alcohol consumption, smoking, and baseline diseases. Results: Risk of death increased for those having probable sarcopenia only (hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.39–1.85) or probable sarcopenia with obesity (HR: 1.36, 95% CI: 1.13–1.64) but not for the obese-only group (HR: 0.92, 95% CI: 0.85–1.01), when compared to non-obese non-sarcopenic individuals. The results were similar regardless of adjustments for covariates or different obesity criteria applied. Conclusion: Probable sarcopenia, whether combined with obesity or not, is associated with increased mortality. Obesity did not increase mortality among older adults. Maintaining muscle strength and identifying older adults at risk of sarcopenia is important for the prevention of premature mortality.

BackgroundNatalizumab is effective in the treatment of multiple sclerosis (MS). In 2021, the European Medicines Agency approved the subcutaneous (SC) variant of natalizumab which can be used instead of intravenous administration. However, the course of drug levels varies between administration routes, and the Food and Drug Administration rejected the request for approval of natalizumab SC for reasons that were not disclosed. Our objective was to evaluate the course of natalizumab trough drug levels in patients who switched from natalizumab intravenous to SC on various treatment intervals.MethodsThe NEXT-MS trial (N=382) investigates personalised treatment of natalizumab, in which infusion intervals are prolonged based on individual natalizumab trough drug levels. In 2021, an amendment was approved allowing participants to switch from intravenous to SC administration with frequent measurements of natalizumab drug levels and antidrug antibodies (ADAs). Results were compared with linear mixed model analyses.ResultsUntil December 2022, 15 participants switched to SC natalizumab. Natalizumab drug levels with SC administration were on average 55% lower compared with intravenous administration (Exp (estimate) 0.45, 95% CI 0.39 to 0.53, pConclusionsNatalizumab trough drug levels can decrease after switching from natalizumab intravenous to SC administration. We advise to monitor trough drug levels in patients with low natalizumab drug levels during intravenous treatment, patients with higher body mass index or patients on extended treatment intervals who switch to SC administration of natalizumab.

Purpose: Recent studies suggest that women are more susceptible to diuretic-induced hyponatremia resulting in hospital admission than men. The aim of this study was to confirm whether these sex differences in hyponatremia-related hospital admissions in diuretic users remain after adjusting for several confounding variables such as age, dose, and concurrent medication. Methods: In a case–control design nested in diuretic users, cases of hyponatremia associated hospital admissions between 2005 and 2017 were identified from the PHARMO Data Network. Cases were 1:10 matched to diuretic users as controls. Odds ratios (OR) with 95%CIs were calculated for women versus men and adjusted for potential confounders (age, number of diuretics, other hyponatremia-inducing drugs, chronic disease score) using unconditional logistic regression analysis. A subgroup analysis was performed for specific diuretic groups (thiazides, loop diuretics and aldosterone antagonists). Results: Women had a statistically significantly higher risk of a hospital admission associated with hyponatremia than men while using diuretics (OR 1.86, 95%CI 1.64–2.11). Adjusting for the potential confounders resulted in an increased risk for women compared to men (ORadj 2.65, 95% CI 2.31–3.04). This higher risk in women was also seen in the three subgroup analyses after adjustment. Conclusion: Our findings show a higher risk of hyponatremia-related hospital admission in women than men while using diuretics. Further research is needed to understand the underlying mechanism of this sex difference to be able to provide sex-specific recommendations.

Objectives: To elicit the relative importance of the benefits and harms of colorectal cancer (CRC) screening among potential screening participants in the Dutch population. Methods: In a consensus meeting with 11 experts, risk reduction of CRC and CRC deaths (benefits) and complications from colonoscopy, stress of receiving positive fecal immunological test (FIT) results, as well as false-positive and false-negative FIT results (harms) were selected as determinant end points to consider during decision making. We conducted an online best-worst scaling survey among adults aged 55 to 75 years from the Dutch Health Care Consumer Panel of The Netherlands Institute for Health Services Research to elicit preference values for these outcomes. The preference values were estimated using conditional logit regression. Results: Of 265 participants, 234 (89%) had ever participated in CRC screening. Compared with the stress of receiving a positive FIT result, the outcome perceived most important was the risk of CRC death (odds ratio [OR] 4.5; 95% confidence interval [CI] 3.9-5.1), followed by risk of CRC (OR 4.1; 95% CI 3.6-4.7), a false-negative FIT result (OR 3.1; 95% CI 2.7-3.5), colonoscopy complications (OR 1.6; 95% CI 1.4-1.8), and a false-positive FIT result (OR 1.4; 95% CI 1.3-1.6). The magnitude of these differences in perceived importance varied according to age, educational level, ethnic background, and whether the individual had previously participated in CRC screening. Conclusion: Dutch men and women eligible for FIT-based CRC screening perceive the benefits of screening to be more important than the harms.

Urbanization and inequalities are two of the major policy themes of our time, intersecting in large cities where social and economic inequalities are particularly pronounced. Large scale street-level images are a source of city-wide visual information and allow for comparative analyses of multiple cities. Computer vision methods based on deep learning applied to street images have been shown to successfully measure inequalities in socioeconomic and environmental features, yet existing work has been within specific geographies and have not looked at how visual environments compare across different cities and countries. In this study, we aim to apply existing methods to understand whether, and to what extent, poor and wealthy groups live in visually similar neighborhoods across cities and countries. We present novel insights on similarity of neighborhoods using street-level images and deep learning methods. We analyzed 7.2 million images from 12 cities in five high-income countries, home to more than 85 million people: Auckland (New Zealand), Sydney (Australia), Toronto and Vancouver (Canada), Atlanta, Boston, Chicago, Los Angeles, New York, San Francisco, and Washington D.C. (United States of America), and London (United Kingdom). Visual features associated with neighborhood disadvantage are more distinct and unique to each city than those associated with affluence. For example, from what is visible from street images, high density poor neighborhoods located near the city center (e.g., in London) are visually distinct from poor suburban neighborhoods characterized by lower density and lower accessibility (e.g., in Atlanta). This suggests that differences between two cities is also driven by historical factors, policies, and local geography. Our results also have implications for image-based measures of inequality in cities especially when trained on data from cities that are visually distinct from target cities. We showed that these are more prone to errors for disadvantaged areas especially when transferring across cities, suggesting more attention needs to be paid to improving methods for capturing heterogeneity in poor environment across cities around the world.

Background Recruiting participants for lifestyle programmes is known to be challenging. Insights into recruitment strategies, enrolment rates and costs are valuable but rarely reported. We provide insight into the costs and results of used recruitment strategies, baseline characteristics and feasibility of at-home cardiometabolic measurements as part of the Supreme Nudge trial investigating healthy lifestyle behaviours. This trial was conducted during the COVID-19 pandemic, requiring a largely remote data collection approach. Potential sociodemographic differences were explored between participants recruited through various strategies and for at-home measurement completion rates. Methods Participants were recruited from socially disadvantaged areas around participating study supermarkets (n = 12 supermarkets) across the Netherlands, aged 30–80 years, and regular shoppers of the participating supermarkets. Recruitment strategies, costs and yields were logged, together with completion rates of at-home measurements of cardiometabolic markers. Descriptive statistics are reported on recruitment yield per used method and baseline characteristics. We used linear and logistic multilevel models to assess the potential sociodemographic differences. Results Of 783 recruited, 602 were eligible to participate, and 421 completed informed consent. Most included participants were recruited via letters/flyers at home (75%), but this strategy was very costly per included participant (89 Euros). Of paid strategies, supermarket flyers were the cheapest (12 Euros) and the least time-invasive (n = 391) were on average 57.6 (SD 11.0) years, 72% were female and 41% had high educational attainment, and they often completed the at-home measurements successfully (lipid profile 88%, HbA1c 94%, waist circumference 99%). Multilevel models suggested that males tended to be recruited more often via word-of-mouth (ORfemales 0.51 (95%CI 0.22; 1.21)). Those who failed the first attempt at completing the at-home blood measurement were older (β 3.89 years (95% CI 1.28; 6.49), whilst the non-completers of the HbA1c (β − 8.92 years (95% CI − 13.62; − 4.28)) and LDL (β − 3.19 years (95% CI − 6.53; 0.09)) were younger. Conclusions Supermarket flyers were the most cost-effective paid strategy, whereas mailings to home addresses recruited the most participants but were very costly. At-home cardiometabolic measurements were feasible and may be useful in geographically widespread groups or when face to face contact is not possible. Trial registration Dutch Trial Register ID NL7064, 30 May 2018, https://trialsearch.who.int/Trial2.aspx?TrialID=NTR7302

Background During COVID-19 lockdown measures, memory clinic patients reported worries for faster cognitive decline, due to loss of structure and feelings of loneliness and depression. We aimed to investigate the impact of the COVID-19 lockdown on rate of cognitive decline in a mixed memory clinic population, compared to matched historical controls. Methods We included patients who visited Alzheimer Center Amsterdam 6 months to 1 week before the first Dutch COVID-19 lockdown, and had a second visit 1 year later, after this lockdown period (n = 113; 66 ± 7 years old; 30% female; n = 55 dementia, n = 31 mild cognitive impairment (MCI), n = 18 subjective cognitive decline (SCD), n = 9 postponed diagnosis). Historical controls (visit in 2016/2017 and second visit 1 year later (n = 640)) were matched 1:1 to lockdown patients by optimal Mahalanobis distance matching (both groups n = 113). Groups were well matched. Differences between lockdown patients and historical controls over time in Mini-Mental State Examination, Trail Making Test part A and B, Rey-Auditory Verbal Learning Test (RAVLT) immediate and delayed recall, and category fluency scores were analyzed using linear mixed effect models with random intercepts. We examined differences in rate of cognitive decline between whole groups, and after stratification in SCD, MCI, and dementia separately. Results Lockdown patients had a faster rate of memory decline compared to controls on both RAVLT immediate [B(SE) = − 2.62 (1.07), p = 0.015] and delayed recall [B(SE) = − 1.07 (0.34), p = 0.002]. Stratification by syndrome diagnosis showed that this effect was largely attributable to non-demented participants, as we observed faster memory decline during lockdown in SCD and MCI (RAVLT immediate [SCD: B(SE) = − 6.85 (2.97), p = 0.027; MCI: B(SE) = − 6.14 (1.78), p = 0.001] and delayed recall [SCD: B(SE) = − 2.45 (1.11), p = 0.035; MCI: B(SE) = − 1.50 (0.51), p = 0.005]), but not in dementia. Conclusion Memory clinic patients, specifically in pre-dementia stages, showed faster memory decline during COVID-19 lockdown, providing evidence that lockdown regulations had a deleterious effect on brain health. In individuals that may have been able to deal with accumulating, subclinical neuropathology under normal and structured circumstances, the additional stress of lockdown regulations may have acted as a “second hit,” resulting in less beneficial disease trajectory.

Background Comorbidities among cancer survivors remain a serious healthcare burden and require appropriate management. Using two widely used frailty indicators, this study aimed to evaluate whether frailty was associated with the incidence risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) among long-term cancer survivors. Methods We included 13,388 long-term cancer survivors (diagnosed with cancer over 5 years before enrolment) free of CVD and 6101 long-term cancer survivors free of T2DM, at the time of recruitment (aged 40–69 years), from the UK Biobank. Frailty was assessed by the frailty phenotype (FP_Frailty, range: 0–5) and the frailty index (FI_Frailty, range: 0–1) at baseline. The incident CVD and T2DM were ascertained through linked hospital data and primary care data, respectively. The associations were examined using Cox proportional hazards regression models. Results Compared with non-frail participants, those with pre-frailty (FP_Frailty [met 1–2 of the components]: hazard ratio [HR]=1.18, 95% confidence interval [CI]: 1.05, 1.32; FI_Frailty [0.10< FI ≤0.21]: HR=1.51, 95% CI: 1.32, 1.74) and frailty (FP_Frailty [met ≥3 of the components]: HR=2.12, 95% CI: 1.73, 2.60; FI_Frailty [FI >0.21]: HR=2.19, 95% CI: 1.85, 2.59) had a significantly higher risk of CVD in the multivariable-adjusted model. A similar association of FI_Frailty with the risk of incident T2DM was observed. We failed to find such an association for FP_Frailty. Notably, the very early stage of frailty (1 for FP_Frailty and 0.1-0.2 for FI_Frailty) was also positively associated with the risk of CVD and T2DM (FI_Frailty only). A series of sensitivity analyses confirmed the robustness of the findings. Conclusions Frailty, even in the very early stage, was positively associated with the incidence risk of CVD and T2DM among long-term cancer survivors, although discrepancies existed between frailty indicators. While the validation of these findings is required, they suggest that routine monitoring, prevention, and interventive programs of frailty among cancer survivors may help to prevent late comorbidities and, eventually, improve their quality of life. Especially, interventions are recommended to target those at an early stage of frailty when healthcare resources are limited.

Immune cell function can be altered by lipids in circulation, a process potentially relevant to lipid-associated inflammatory diseases including atherosclerosis and rheumatoid arthritis. To gain further insight in the molecular changes involved, we here perform a transcriptome-wide association analysis of blood triglycerides, HDL cholesterol, and LDL cholesterol in 3229 individuals, followed by a systematic bidirectional Mendelian randomization analysis to assess the direction of effects and control for pleiotropy. Triglycerides are found to induce transcriptional changes in 55 genes and HDL cholesterol in 5 genes. The function and cell-specific expression pattern of these genes implies that triglycerides downregulate both cellular lipid metabolism and, unexpectedly, allergic response. Indeed, a Mendelian randomization approach based on GWAS summary statistics indicates that several of these genes, including interleukin-4 (IL4) and IgE receptors (FCER1A, MS4A2), affect the incidence of allergic diseases. Our findings highlight the interplay between triglycerides and immune cells in allergic disease.

Background Physical activity (PA) levels might be a simple overall physical function indicator of recovery in acutely hospitalized older adults; however it is unknown which amount and level of PA is associated with recovery. Our objective was to evaluate the amount and level of post discharge PA and its optimum cut-off values associated with recovery among acutely hospitalized older adults and stratified for frailty. Methods We performed a prospective observational cohort study including acutely hospitalized older adults (≥ 70 years). Frailty was assessed using Fried’s criteria. PA was assessed using Fitbit up to one week post discharge and quantified in steps and minutes light, moderate or higher intensity. The primary outcome was recovery at 3-months post discharge. ROC-curve analyses were used to determine cut-off values and area under the curve (AUC), and logistic regression analyses to calculate odds ratios (ORs). Results The analytic sample included 174 participants with a mean (standard deviation) age of 79.2 (6.7) years of whom 84/174 (48%) were frail. At 3-months, 109/174 participants (63%) had recovered of whom 48 were frail. In all participants, determined cut-off values were 1369 steps/day (OR: 2.7, 95% confidence interval [CI]: 1.3–5.9, AUC 0.7) and 76 min/day of light intensity PA (OR: 3.9, 95% CI: 1.8–8.5, AUC 0.73). In frail participants, cut-off values were 1043 steps/day (OR: 5.0, 95% CI: 1.7–14.8, AUC 0.72) and 72 min/day of light intensity PA (OR: 7.2, 95% CI: 2.2–23.1, AUC 0,74). Determined cut-off values were not significantly associated with recovery in non-frail participants. Conclusions Post-discharge PA cut-offs indicate the odds of recovery in older adults, especially in frail individuals, however are not equipped for use as a diagnostic test in daily practice. This is a first step in providing a direction for setting rehabilitation goals in older adults after hospitalization.

Background To evaluate the effects of a shared decision making (SDM) intervention for older adults with multiple chronic conditions (MCCs). Methods A pragmatic trial evaluated the effects of the SDMMCC intervention, existing of SDM training for nine geriatricians in two hospitals and a preparatory tool for patients. A prospective pre-intervention post-intervention multi-center clinical study was conducted in which an usual care group of older patients with MCC and their informal caregivers was included before the implementation of the intervention and a new cohort of patients and informal caregivers after the implementation of the intervention. SDM was observed using the OPTIONMCC during video-recorded consultations. Patient- and caregivers reported outcomes regarding their role in SDM, involvement, perceived SDM and decisional conflict were measured. The differences between groups regarding the level of observed SDM (OPTIONMCC) were analyzed with a mixed model analysis. Dichotomous patient-reported outcomes were analyzed with a logistic mixed model. Results From two outpatient geriatric clinics 216 patients with MCCs participated. The mean age was 77.3 years, and 56.3% of patients were female. No significant difference was found in the overall level of SDM as measured with the OPTIONMCC or in patient-reported outcomes. However, at item level the items discussing ‘goals’, ‘options’, and ‘decision making’ significantly improved after the intervention. The items discussing ‘partnership’ and ‘evaluating the decision-making process’ showed a significant decrease. Fifty-two percent of the patients completed the preparatory tool, but the results were only discussed in 12% of the consultations. Conclusion This study provides scope for improvement of SDM in geriatrics. Engaging older adults with MCCs and informal caregivers in the decision making process should be an essential part of SDM training for geriatricians, beyond the SDM steps of explaining options, benefits and harms. More attention should be paid to the integration of preparatory work in the consultation.

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

The original article [1] contained the following errors with their respective amendments: 1) Abstract, lines 48 and 49: “Median TDI score on SST was 26.8 (IQR 23.6-29.3) in the placebo group and 28.8 (IQR 24.0-30.9) in the prednisolone group, with a median difference of 2.0 (95% CI 0.75 to 1.5).” to “Median TDI score on SST was 26.8 (IQR 23.6-29.3) in the placebo group and 28.8 (IQR 24.0-30.9) in the prednisolone group, with a median difference of - 1.5 (-3.0 to 0.25).” 2) Outcome, line 233-235: “Median TDI score was 26.8 (IQR 23.6- 29.3) in the placebo group and 28.8 (IQR 24.0- 30.9) in the prednisolone group, with a median difference of 2.0 (95% CI 0.75 to 1.5, p = 0.10).” to “Median TDI score was 26.8 (IQR 23.6- 29.3) in the placebo group and 28.8 (IQR 24.0- 30.9) in the prednisolone group, with a median difference of - 1.5 (-3.0 to 0.25).” 3) Line 237-238: "Self-reported smell function on VAS-score was 3.2 (IQR 1.8- 6.5) in the placebo group and 3.6 (IQR 1.0- 5.8) in the prednisolone group with a median difference of 0.45 (95% CI 1.1 to -1.2, p = 0.53)." to "Self-reported smell function on VAS-score was 3.2 (IQR 1.8- 6.5) in the placebo group and 3.6 (IQR 1.0- 5.8) in the prednisolone group with a median difference of 0.3 (95% CI -0.9 to -1.3, p = 0.53)." 4) Line 240-242: “Self-reported taste function on VAS-score was 5.6 (IQR 2.3- 7.6) in the placebo group and 5.0 (IQR 2.0- 7.8) in the prednisolone group with a median difference of 0.25 (95% CI 0.1 to -0.2, p = 0.80).” to “Self-reported taste function on VAS-score was 5.6 (IQR 2.3- 7.6) in the placebo group and 5.0 (IQR 2.0- 7.8) in the prednisolone group with a median difference of 0.1 (95% CI -1.0 to 1.3, p = 0.80)”.

Although various neurodegenerative disorders have been associated with coeliac disease (CD), the underlying neuropathological link between these brain and gut diseases remains unclear. We postulated that the neuronal damage sporadically observed in CD patients is immune-mediated. Our aim was to determine if the loss of neurons, especially Purkinje cells, coincides with microglia activation and T- and B-cell infiltration in the cerebellum of patients with CD and a concomitant idiopathic neurological disease affecting the cerebellum (NeuroCD). Post-mortem cerebellar tissue was collected of validated NeuroCD cases. Gender- and age-matched genetic spinocerebellar ataxia (SCA) controls and non-neurological controls (NNC) were selected based on clinical reports and pathological findings. Cerebellar tissue of seventeen patients was included (6 NeuroCD, 5 SCA, 6 NNC). In SCA cases we found that the Purkinje cell layer was 58.6% reduced in comparison with NNC. In NeuroCD cases this reduction was even more prominent with a median reduction of 81.3% compared to NNC. Marked increased numbers of both CD3+ and CD8+ cells were observed in the NeuroCD but not in SCA patients. This coincided with significantly more microglial reactivity in NeuroCD patients. These findings demonstrate that the massive loss of Purkinje cells in the cerebellum of neuro CD patients is accompanied by local innate and T-cell mediated immune responses.

Background Opioid-induced constipation (OIC) is a common symptom in cancer patients treated with opioids with a prevalence of up to 59%. International guidelines recommend standard laxatives such as macrogol/electrolytes and magnesium hydroxide to prevent OIC, although evidence from randomized controlled trials is largely lacking. The aim of our study is to compare magnesium hydroxide with macrogol /electrolytes in the prevention of OIC in patients with incurable cancer and to compare side-effects, tolerability and cost-effectiveness. Methods Our study is an open-label, randomized, multicenter study to examine if magnesium hydroxide is non-inferior to macrogol/electrolytes in the prevention of OIC. In total, 330 patients with incurable cancer, starting with opioids for pain management, will be randomized to treatment with either macrogol/electrolytes or magnesium hydroxide. The primary outcome measure is the proportion of patients with a score of The Rome IV criteria for constipation, side effects of and satisfaction with laxatives, pain scores, quality of life (using the EQ-5D-5L), daily use of laxatives and escape medication, and cost-effectiveness will also be assessed. Discussion In this study we aim to examine if magnesium hydroxide is non-inferior to macrogol/electrolytes in the prevention of OIC. The outcome of our study will contribute to prevention of OIC and scientific evidence of guidelines on (opioid-induced) constipation. Trial registration This trial is registered at clinicaltrials.gov: NCT05216328 and in the Dutch trial register: NTR80508. EudraCT number 2022–000408-36.

Background Providing individualized care based on the context and preferences of the patient is important. Knowledge on both prognostic risk stratification and blended eHealth care in musculoskeletal conditions is increasing and seems promising. Stratification can be used to match patients to the most optimal content and intensity of treatment as well as mode of treatment delivery (i.e. face-to-face or blended with eHealth). However, research on the integration of stratified and blended eHealth care with corresponding matched treatment options for patients with neck and/or shoulder complaints is lacking. Methods This study was a mixed methods study comprising the development of matched treatment options, followed by an evaluation of the feasibility of the developed Stratified Blended Physiotherapy approach. In the first phase, three focus groups with physiotherapists and physiotherapy experts were conducted. The second phase investigated the feasibility (i.e. satisfaction, usability and experiences) of the Stratified Blended Physiotherapy approach for both physiotherapists and patients in a multicenter single-arm convergent parallel mixed methods feasibility study. Results In the first phase, matched treatment options were developed for six patient subgroups. Recommendations for content and intensity of physiotherapy were matched to the patient’s risk of persistent disabling pain (using the Keele STarT MSK Tool: low/medium/high risk). In addition, selection of mode of treatment delivery was matched to the patient’s suitability for blended care (using the Dutch Blended Physiotherapy Checklist: yes/no). A paper-based workbook and e-Exercise app modules were developed as two different mode of treatment delivery options, to support physiotherapists. Feasibility was evaluated in the second phase. Physiotherapists and patients were mildly satisfied with the new approach. Usability of the physiotherapist dashboard to set up the e-Exercise app was considered ‘OK’ by physiotherapists. Patients considered the e-Exercise app to be of ‘best imaginable’ usability. The paper-based workbook was not used. Conclusion Results of the focus groups led to the development of matched treatment options. Results of the feasibility study showed experiences with integrating stratified and blended eHealth care and have informed amendments to the Stratified Blended Physiotherapy approach for patients with neck and/or shoulder complaints ready to use within a future cluster randomized trial.

Background Neuropsychiatric symptoms (NPS) are prevalent in the early clinical stages of Alzheimer’s disease (AD) according to proxy-based instruments. Little is known about which NPS clinicians report and whether their judgment aligns with proxy-based instruments. We used natural language processing (NLP) to classify NPS in electronic health records (EHRs) to estimate the reporting of NPS in symptomatic AD at the memory clinic according to clinicians. Next, we compared NPS as reported in EHRs and NPS reported by caregivers on the Neuropsychiatric Inventory (NPI). Methods Two academic memory clinic cohorts were used: the Amsterdam UMC (n = 3001) and the Erasmus MC (n = 646). Patients included in these cohorts had MCI, AD dementia, or mixed AD/VaD dementia. Ten trained clinicians annotated 13 types of NPS in a randomly selected training set of n = 500 EHRs from the Amsterdam UMC cohort and in a test set of n = 250 EHRs from the Erasmus MC cohort. For each NPS, a generalized linear classifier was trained and internally and externally validated. Prevalence estimates of NPS were adjusted for the imperfect sensitivity and specificity of each classifier. Intra-individual comparison of the NPS classified in EHRs and NPS reported on the NPI were conducted in a subsample (59%). Results Internal validation performance of the classifiers was excellent (AUC range: 0.81–0.91), but external validation performance decreased (AUC range: 0.51–0.93). NPS were prevalent in EHRs from the Amsterdam UMC, especially apathy (adjusted prevalence = 69.4%), anxiety (adjusted prevalence = 53.7%), aberrant motor behavior (adjusted prevalence = 47.5%), irritability (adjusted prevalence = 42.6%), and depression (adjusted prevalence = 38.5%). The ranking of NPS was similar for EHRs from the Erasmus MC, although not all classifiers obtained valid prevalence estimates due to low specificity. In both cohorts, there was minimal agreement between NPS classified in the EHRs and NPS reported on the NPI (all kappa coefficients Conclusions NLP classifiers performed well in detecting a wide range of NPS in EHRs of patients with symptomatic AD visiting the memory clinic and showed that clinicians frequently reported NPS in these EHRs. Clinicians generally reported more NPS in EHRs than caregivers reported on the NPI.

Background: It is unclear whether sex or age modify the association of glucocorticoid (GC) use with reduced bone mineral density (BMD) in patients with rheumatoid arthritis (RA). Methods: We studied cross-sectional data of RA patients with current or previous GC treatment in a single center cohort study (Rh-GIOP cohort). Our primary outcome was the minimum T-score (measured by DXA) of either lumbar spine, total femur, or femoral neck. Current GC dose was the main exposure; cumulative GC dose and cumulative duration of GC use were also assessed. Following a predefined statistical analysis plan, linear regression analyses with adjustment for confounders assessed whether the association of GC use with BMD was modified by sex (men versus women) or age (≥ 65 versus < 65 years). Results: Four hundred eighty-three patients with RA (mean age 64 ± 12 years, 80% women) were included. 33% were not currently taking GCs, 32% were treated with a dose of 5 mg/d prednisone equivalent and 11% with more than 7.5 mg/d. 23% of patients had osteoporosis by DXA (minimum T-score ≤ -2.5). The slope, i.e., the association between changes in minimum T-scores with 1 mg/d change in current GC dose, was similar in men and women (-0.07 and -0.04, respectively; difference -0.03 [-0.11 to 0.04]; p for interaction = 0.41). Slopes were also similar for elderly and non-elderly patients (-0.03 and -0.04, respectively; difference -0.01 [-0.06 to 0.05]; p for interaction = 0.77). Using cumulative dose and duration of use as exposures did not lead to substantial changes of these results. Conclusions: In our sample, the association of GC use with reduced BMD in RA was not modified by sex or age.

Intensive longitudinal data can be used to explore important associations and patterns between various types of inputs and outcomes. Nonlinear relations and irregular measurement occasions can pose problems to develop an accurate model for these kinds of data. This paper focuses on the development, fitting and evaluation of a prediction model with irregular intensive longitudinal data. A three-step process for developing a prediction tool for (daily) monitoring and prediction is outlined and illustrated for intensive weight measurements in piglets. Step 1 addresses a nonlinear relation in the data by developing and applying a normalizing transformation. Step 2 addresses the intermittent nature of the time points by aligning the measurement times to a common time grid with a broken-stick model. Step 3 addresses the prediction problem by selecting and evaluating inputs and covariates in the model to obtain accurate predictions. The final model predicts future outcomes accurately, while allowing for nonlinearities between input and output and for different measurement histories of individuals. The methodology described can be used to develop a tool to deal with intensive irregular longitudinal data that uses the available information in an optimal way. The resulting tool demonstrated to perform well for piglet weight prediction and can be adapted to many different applications.

Background Smoking among people with severe mental illness (SMI) is highly prevalent and strongly associated with poor physical health. Currently, evidence-based smoking cessation interventions are scarce and need to be integrated into current mental health care treatment guidelines and clinical practice. Therefore, the present study aims to evaluate the implementation and effectiveness of a smoking cessation intervention in comparison with usual care in people with SMI treated by Flexible Assertive Community Treatment (FACT) teams in the Netherlands. Methods A pragmatic, cluster-randomised controlled trial with embedded process evaluation will be conducted. Randomisation will be performed at the level of FACT teams, which will be assigned to the KISMET intervention or a control group (care as usual). The intervention will include pharmacological treatment combined with behavioural counselling and peer support provided by trained mental health care professionals. The intervention was developed using a Delphi study, through which a consensus was reached on the core elements of the intervention. We aim to include a total of 318 people with SMI (aged 18–65 years) who smoke and desire to quit smoking. The primary outcome is smoking status, as verified by carbon monoxide measurements and self-report. The secondary outcomes are depression and anxiety, psychotic symptoms, physical fitness, cardiovascular risks, substance use, quality of life, and health-related self-efficacy at 12 months. Alongside the trial, a qualitative process evaluation will be conducted to evaluate the barriers to and facilitators of its implementation as well as the satisfaction and experiences of both patients and mental health care professionals. Discussion The results of the KISMET trial will contribute to the evidence gap of effective smoking cessation interventions for people treated by FACT teams. Moreover, insights will be obtained regarding the implementation process of the intervention in current mental health care. The outcomes should advance the understanding of the interdependence of physical and mental health and the gradual integration of both within the mental health care system. Trial registration Netherlands Trial Register, NTR9783. Registered on 18 October 2021.

Background There is a need for novel fluid biomarkers tracking neuroinflammatory responses in Alzheimer’s disease (AD). Our recent cerebrospinal fluid (CSF) proteomics study revealed that migration inhibitory factor (MIF) and soluble triggering receptor expressed on myeloid cells 1 (sTREM1) increased along the AD continuum. We aimed to assess the potential use of these proteins, in addition to sTREM2, as CSF biomarkers to monitor inflammatory processes in AD. Methods We included cognitively unimpaired controls (n = 67, 63 ± 9 years, 24% females, all amyloid negative), patients with mild cognitive impairment (MCI; n = 92, 65 ± 7 years, 47% females, 65% amyloid positive), AD (n = 38, 67 ± 6 years, 8% females, all amyloid positive), and DLB (n = 50, 67 ± 6 years, 5% females, 54% amyloid positive). MIF, sTREM1, and sTREM2 levels were measured by validated immunoassays. Differences in protein levels between groups were tested with analysis of covariance (corrected for age and sex). Spearman correlation analysis was performed to evaluate the association between these neuroinflammatory markers with AD-CSF biomarkers (Aβ42, tTau, pTau) and mini-mental state examination (MMSE) scores. Results MIF levels were increased in MCI (p p p > 0.05) compared to controls. Levels of sTREM1 were specifically increased in AD compared to controls (p p p > 0.05), while sTREM2 levels were increased specifically in MCI compared to all other groups (all p Conclusion Inflammatory-related proteins show diverse expression profiles along different AD stages, with increased protein levels in the MCI stage (MIF and sTREM2) and AD stage (MIF and sTREM1). The associations of these inflammatory markers primarily with CSF pTau levels indicate an intertwined relationship between tau pathology and inflammation. These neuroinflammatory markers might be useful in clinical trials to capture dynamics in inflammatory responses or monitor drug–target engagement of inflammatory modulators.

The original version of this Article omitted from the author list the 212th author Patrizia Mecocci, who is from the Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy. Consequently, the “Sample Contribution” section of Author Contributions was updated to add “P.M” between “P.D.” and “R.C.”. Additionally, the original version of this Article contained the incorrect affiliation for author Patrick Gavin Kehoe, which incorrectly read “German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany”. The correct version replaces this affiliation with “Bristol Medical School (THS), University of Bristol, Southmead Hospital, Bristol, UK”. This has been corrected in both the PDF and HTML versions of the Article.

Background The Patient-Reported Outcomes Measurement Information System (PROMIS®) has the potential to harmonize the measurement of health-related quality of life (HRQL) across medical conditions. We evaluated responsiveness and minimal important change (MIC) of seven Dutch-Flemish PROMIS computerized adaptive tests (CAT) in Dutch patients with advanced chronic kidney disease (CKD). Methods CKD patients (eGFR 2) completed at baseline and after 6 months seven PROMIS CATs (assessing physical function, pain interference, fatigue, sleep disturbance, anxiety, depression, and ability to participate in social roles and activities), Short Form Health Survey 12 (SF-12), PROMIS Pain Intensity single item, Dialysis Symptom Index (DSI), and Global Rating Scales (GRS) of change. Responsiveness was assessed by testing predefined hypotheses about expected correlations among measures, area under the ROC Curve, and effect sizes. MIC was determined with predictive modelling. Results 207 patients were included; 186 (90%) completed the follow-up. Most results were in accordance with expectations (70–91% of hypotheses confirmed), with some exceptions for PROMIS Anxiety and Ability to Participate (60% and 42% of hypotheses confirmed, respectively). For PROMIS Anxiety and Depression correlations with the GRS were too low (0.04 and 0.20, respectively) to calculate a MIC. MIC values, representing minimal important deterioration, ranged from 0.4 to 2.5 T-score points for the other domains. Conclusion We found sufficient responsiveness of PROMIS CATs Physical Function, Fatigue, Sleep Disturbance, and Depression. The results for PROMIS CATs Pain Interference were almost sufficient, but some results for Anxiety and Ability to Participate in Social Roles and Activities were not as expected. Reported MIC values should be interpreted with caution because most patients did not change.

This study set out to evaluate the association between job demands at baseline and physical performance over a six-year period across three cohorts of older Dutch workers examined 10 years apart. Data were drawn from three cohorts (1992–1999, 2002–2009 and 2012–2019) of the Longitudinal Aging Study Amsterdam. Individuals aged 55–65 years from each cohort who worked for pay were included (n = 274, n = 416, n = 618, respectively). Physical performance was measured using gait speed and chair stand performance. A population-based job exposure matrix was used to indicate levels of exposure probability of physical (use of force and repetitive movements) and psychosocial (cognitive demands and time pressure) job demands. We found that psychosocial job demands increased and physical demands decreased across the three cohorts. No between cohort differences were found for how job demands affected changes in physical performance over follow-up. For men, faster decline in gait speed was observed when comparing higher and lower use of force at baseline (β −0.012, 95% CI −0.021, −0.004). Greater use of force and repetitive movements were associated with faster decline in chair stand performance (β −0.012, 95% CI −0.020, −0.004 and β −0.009, 95% CI −0.017, −0.001, respectively). In women, no association of job demands on change in physical performance was observed. The study concluded that higher physical job demands were associated with stronger decline in physical performance across six years for men in all cohorts, while no associations were found among women. peerReviewed

Background Age-related changes in frailty have been documented in the literature. However, the evidence regarding changes in frailty prior to death is scarce. Understanding patterns of frailty progression as individuals approach death could inform care and potentially lead to interventions to improve individual’s well-being at the end of life. In this paper, we estimate the progression of frailty in the years prior to death. Methods Using data from 8,317 deceased participants of the Survey of Health, Ageing, and Retirement in Europe, we derived a 56-item Frailty Index. In a coordinated analysis of repeated measures of the frailty index in 14 countries, we fitted growth curve models to estimate trajectories of frailty as a function of distance to death controlling both the level and rate of frailty progression for age, sex, years to death and dementia diagnosis. Results Across all countries, frailty before death progressed linearly. In 12 of the 14 countries included in our analyses, women had higher levels of frailty close to the time of death, although they progressed at a slower rate than men (e.g. Switzerland (-0.008, SE = 0.003) and Spain (-0.004, SE = 0.002)). Older age at the time of death and incident dementia were associated with higher levels and increased rate of change in frailty, whilst higher education was associated with lower levels of frailty in the year preceding death (e.g. Denmark (0.000, SE = 0.001)). Conclusion The progression of frailty before death was linear. Our results suggest that interventions aimed at slowing frailty progression may need to be different for men and women. Further longitudinal research on individual patterns and changes of frailty is warranted to support the development of personalized care pathways at the end of life.

Alzheimer's disease (AD) is a major healthcare challenge with no curative treatment at present. To address this challenge, we need a paradigm shift, where we focus on pre-dementia stages of AD. In this Perspective, we outline a strategy to move towards a future with personalized medicine for AD by preparing for and investing in effective and patient-orchestrated diagnosis, prediction and prevention of the dementia stage. While focusing on AD, this Perspective also discusses studies that do not specify the cause of dementia. Future personalized prevention strategies encompass multiple components, including tailored combinations of disease-modifying interventions and lifestyle. By empowering the public and patients to be more actively engaged in the management of their health and disease and by developing improved strategies for diagnosis, prediction and prevention, we can pave the way for a future with personalized medicine, in which AD pathology is stopped to prevent or delay the onset of dementia.This Perspective outlines a strategy to move towards a future with personalized medicine for Alzheimer's disease by empowering patients in orchestrating diagnosis, prediction and prevention of the onset of dementia.

Objective: To evaluate differences regarding the number of treatment sessions, costs, and outcomes (including relapses) between a regular payment-per-session system and the recently introduced product payment system in The Netherlands. Design: Prospective cohort study. Setting: Dutch physical therapy practices in primary care over a 2-year period. Participants: 16,103 patients with low back pain (LBP). Intervention: The new product payment system is compared with the regular payment-per-session system. Main Outcome Measures: Pain, disability, recovery, number of physical therapy sessions, therapy duration, costs (per episode), and LBP relapse. Results: At baseline, we found greater pain and disability scores associated with an increased risk profile in both payment systems. With regard to the payment systems, we found greater costs (€283.8 vs €210.8) and a greater percentage of relapse (4.5% vs 2.8%) for the product payment system compared with the payment-per-session system. Comparing the 2 payment systems within each risk strata, we found no significant differences, except for a decrease in pain in the medium-risk stratum. Concerning the therapy characteristics, we found that in the payment-per-session group, the therapy took 6 days longer for low-risk patients (median 27 vs 21 days) and 7 days shorter for high-risk patients (median 42 vs 49 days) compared with the product payment group. Moreover, the mean number of sessions in the payment-per-session group was greater for low-risk patients (5.4 vs 4.8 sessions) and lower for high-risk patients (7.7 vs 8.1 sessions) compared with the payment-per-session group. Finally, the costs were significantly greater in all strata of the product payment group compared with the payment-per-session group. Conclusions: The 2 payment systems are largely comparable regarding patient outcomes, therapy duration, and treatment sessions. Both the average cost per patient per LBP episode and the number of relapses in the product payment system are statistically significantly greater than in the payment-per-session system.

Objectives: Minimal important difference (MID), the smallest change or difference that patients perceive as important, aids interpretation of change in patient-reported outcome measure (PROM) scores. A credibility instrument that assesses the methodological rigor of an anchor-based MID includes one core item addressing the correlation between the PROM and the anchor. However, the majority of MID studies in the literature fail to report the correlation. To address this issue, we extended the anchor-based MID credibility instrument by adding an item addressing construct proximity as an alternative to the correlation item. Study Design and Setting: Informed by an MID methodological survey, we added an alternative item—a subjective assessment of similarity of the constructs (i.e., construct proximity) between PROM and anchor—to the correlation item and generated principles for the assessment. We sampled 101 MIDs and analyzed the assessments performed by each pair of raters. By calculating weighted Cohen's kappa, we assessed the reliability of the assessments. Results: Construct proximity assessment is based on the anticipated association between the anchor and PROM constructs: the closer the anticipated association, the higher the rating. Our detailed principles address the most frequently used anchors: transition ratings, measures of satisfaction, other PROMs, and clinical measures. The assessments showed acceptable agreement (weighted kappa 0.74, 95% CI 0.55–0.94) between raters. Conclusion: In the absence of a reported correlation coefficient, construct proximity assessment provides a useful alternative in the credibility assessment of anchor-based MID estimates.

STUDY QUESTION Does a short interval (i.e. ≤90 min), compared to a long interval (i.e. ≥180 min), between semen collection and intrauterine insemination (IUI) increase the cumulative chance of an ongoing pregnancy after six IUI cycles? SUMMARY ANSWER A long interval between semen collection and IUI resulted in a borderline significant improvement in cumulative ongoing pregnancies and a statistically significant shorter time to pregnancy. WHAT IS KNOWN ALREADY Retrospective studies assessing the effect of the time interval between semen collection and IUI on pregnancy outcomes have shown inconclusive results. Some studies have indicated a beneficial effect of a short interval between semen collection and IUI on IUI outcomes, while others have not found any differences. To date, no prospective trials have been published on this subject. STUDY DESIGN, SIZE, DURATION The study was performed as a non-blinded, single-center RCT with 297 couples undergoing IUI treatment in a natural or stimulated cycle. The study was conducted between February 2012 and December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Couples with unexplained or mild male subfertility and an indication for IUI were randomly assigned for up to six IUI cycles into either the control group (long interval, i.e. 180 min or more between semen collection and insemination) or the study group (short interval, i.e. insemination as soon as possible after semen processing and within 90 min of semen collection). The study was carried out in an academic hospital-based IVF center in the Netherlands. The primary endpoint of the study was ongoing pregnancy rate per couple, defined as a viable intrauterine pregnancy at 10 weeks after insemination. MAIN RESULTS AND THE ROLE OF CHANCE In the short interval group, 142 couples were analyzed versus 138 couples in the long interval group. In the intention-to-treat (ITT) analysis, the cumulative ongoing pregnancy rate was significantly higher in the long interval group (71/138; 51.4%) compared to that in the short interval group (56/142; 39.4%; relative risks 0.77; 95% CI 0.59–0.99; P = 0.044). The time to pregnancy was significantly shorter in the long interval group (log-rank test, P = 0.012). A Cox regression analysis showed similar results (adjusted hazard ratio 1.528, 95% CI 1.074–2.174, P = 0.019). LIMITATIONS, REASONS FOR CAUTION Limitations of our study are the non-blinded design, the long inclusion and follow-up period of nearly seven years and the large number of protocol violations, especially because they predominantly occurred in the short interval group. The non-significant results in the per-protocol (PP) analyses and the weaknesses of the study should be taken into account in the assessment of the borderline significance of the results in the ITT analyses. WIDER IMPLICATIONS OF THE FINDINGS Because it is not necessary to perform the IUI immediately after semen processing, there can be more time available to choose the optimum work-flow and clinic occupancy. Clinics and laboratories should find their optimal timing of insemination, considering the time between human chorionic gonadotropin injection and insemination in relation to the sperm preparation techniques used as well as the storage time and conditions until insemination. STUDY FUNDING/COMPETING INTEREST(S) There were no external funding and no competing interests to declare. TRIAL REGISTRATION NUMBER Dutch trial registry, trial registration number NTR3144. TRIAL REGISTRATION DATE 14 November 2011. DATE OF FIRST PATIENT’S ENROLLMENT 5 February 2012.

Objectives: Preventive measures against COVID-19 are essential for pregnant women. Pregnant women are particularly vulnerable to emerging infectious pathogens due to alterations in their physiology. We aimed to determine the optimum timing of vaccination to protect pregnant women and their neonates from COVID-19. Methods: A prospective observational longitudinal cohort study in pregnant women who received COVID-19 vaccination. We collected blood samples to evaluate levels of antispike, receptor binding domain and nucleocapsid antibodies against SARS-CoV-2 before vaccination and 15 days after the first and second vaccination. We determined the neutralizing antibodies from mother-infant dyads in maternal and umbilical cord blood at birth. If available, immunoglobulin A was measured in human milk. Results: We included 178 pregnant women. Median antispike immunoglobulin G levels increased significantly from 1.8 to 5431 binding antibody units/ml and receptor binding domain from 6 to 4466 binding antibody units/ml. Virus neutralization showed similar results between different weeks of gestation at vaccination (P >0.3). Conclusion: We advise vaccination in the early second trimester of pregnancy for the optimum balance between the maternal antibody response and placental antibody transfer to the neonate.

Background: The first HPV-vaccine eligible cohorts in the Netherlands will enter the cervical screening program in 2023. However, a substantial number of young women already have had a cervical sample taken before entry into the regular screening program. This study was initiated to explore early effects of HPV vaccination on detection of cytological abnormalities in cervical samples of women younger than the screening age. Methods: Results of cervical samples were obtained from the Dutch National Pathology Databank (PALGA) and were linked to the women's HPV vaccination status from the national vaccination registry (Praeventis) (N = 42,171). Occurrence of low-grade and high-grade squamous intraepithelial lesions or worse (LSIL and HSIL+) and high-risk HPV positive tests (hrHPV) in the first cervical sample were compared between vaccinated and unvaccinated women by multivariable logistic regression analysis, corrected for age at cervical sampling and age of vaccination (12/13 years, ≥ = 14 years). Results: For fully vaccinated women (three- or two-dose schedule), statistically significant reductions were seen for all outcomes compared to unvaccinated women (hrHPV: adjusted OR, 0.70, 95% CI, 0.63–0.79; LSIL: 0.70, 0.61–0.80; HSIL+: 0.39, 0.30–0.51). Conclusions: By linking nation-wide registries on pathology and vaccination, we show significant beneficial early effects of HPV-vaccination on LSIL, HSIL+, CIN3/AIS/carcinoma and hrHPV detection in young women upto 24 years of age who have a cervical sample taken before entry into the cervical cancer screening program.

QUESTION: Can existing post-treatment prognostic models for predicting neck pain recovery (primarily in terms of disability and secondarily in terms of pain intensity and perceived improvement) be externally validated and updated at the end of the treatment period and at 6 and 12 weeks of follow-up in a new Dutch cohort of people with neck pain treated with guideline-based usual care physiotherapy?DESIGN: External validation and model updating in a new prospective cohort of three previously developed prognostic models.PARTICIPANTS: People with (sub)acute neck pain and registered for primary care physiotherapy treatment.OUTCOME MEASURES: Recovery of disability, pain intensity, and perceived recovery at 6 and 12 weeks and at the end of the treatment period.RESULTS: Discriminative performance (c-statistic) of the disability model at 6 weeks was 0.73 (95% CI 0.69 to 0.77) and reasonably well calibrated after intercept recalibration. The disability model at 12 weeks and at the end of the treatment period showed discriminative c-statistic performance values of 0.69 (95% CI 0.64 to 0.73) and 0.68 (95% CI 0.63 to 0.72), respectively, and was well calibrated. Pain models and perceived recovery models did not reach acceptable performance. Cervical mobility added value to the disability models and pain catastrophising to the disability and pain models at 6 weeks.DISCUSSION: Broad external validation of the disability model was successful in people with (sub)acute neck pain and clinicians may use this model in clinical practice with reasonable accuracy. Further research is required to assess the disability model's clinical impact and generalisability, and to identify additional valuable model predictors.REGISTRATION: https://osf.io/a6r3k/.

BACKGROUND: Platelet RNA sequencing has been shown to accurately detect cancer in previous studies. OBJECTIVES: To compare the diagnostic accuracy of platelet RNA sequencing with standard-of-care limited cancer screening in patients with unprovoked venous thromboembolism (VTE). METHODS: Patients aged ≥40 years with unprovoked VTE were recruited at 13 centers and followed for 12 months for cancer. Participants underwent standard-of-care limited cancer screening, and platelet RNA sequencing analysis was performed centrally at study end for cases and selected controls. Sensitivity and specificity were calculated, using the predefined primary positivity threshold of 0.54 for platelet RNA sequencing aiming at 86% test sensitivity, and an additional predefined threshold of 0.89 aiming at 99% test specificity. RESULTS: A total of 476 participants were enrolled, of whom 25 (5.3%) were diagnosed with cancer during 12-month follow-up. For each cancer patient, 3 cancer-free patients were randomly selected for the analysis. The sensitivity of limited screening was 72% (95% CI, 52-86) at a specificity of 91% (95% CI, 82-95). The area under the receiver operator characteristic for platelet RNA sequencing was 0.54 (95% CI, 0.41-0.66). At the primary positivity threshold, all patients had a positive test, for a sensitivity estimated at 100% (95% CI, 87-99) and a specificity of 8% (95% CI, 3.7-16.4). At the secondary threshold, sensitivity was 68% (95% CI, 48-83; p value compared with limited screening 0.71) at a specificity of 36% (95% CI, 26-47). CONCLUSION: Platelet RNA sequencing had poor diagnostic accuracy for detecting occult cancer in patients with unprovoked VTE with the current algorithm. ispartof: J Thromb Haemost vol:21 issue:4 pages:905-916 ispartof: location:England status: published

Background: Knowledge about lentigo maligna (melanoma) (LM/LMM) and its associated prognostic clinicopathological characteristics are limited compared to that of non-LM/LMM subtypes. The current study aimed to determine the clinical relevance of the LM/LMM subtype and its influence on recurrence and survival outcomes. Methods: All consecutive cases of primary cutaneous head and neck LM/LMM treated by wide local excision over a ten-year period were retrospectively reviewed and compared to non-LM/LMM. Clinical outcome and prognostic factors were assessed by cumulative incidence and competing risk analyses. Results: A total of 345 patients were identified. Specific clinicopathological characteristics such as lower median Breslow thickness (1.6 mm versus 2.1 mm; P = 0.013), association with diagnostic sampling errors (17.3% versus 5.2%; P = 0.01), and increased risk of local recurrences due to incomplete resection (18.7% versus 2.3%; P < 0.001), were significantly associated with LM/LMM. Guideline adherence was similar between the two study groups. The positive nodal status at baseline for LMM was low compared to non-LM/LMM (4.2% vs 17.9%; P = 0.037). The LMM subtype, facial localization, and reduced surgical margins (i.e., guideline non-adherence) were not shown to be independent prognostic factors for disease-free, melanoma-specific, or overall survival after correction for competing risks such as patient age and Breslow thickness. Conclusions: The LMM subtype was not shown to be prognostically different from non-LM/LMM when corrected for other variables of influence such as patient age and Breslow thickness. Reduced resection margins did not seem to affect disease-free, and melanoma-specific survival and warrant LM/LMM-specific guidelines. Further research is needed to evaluate the value of SLNB in LMM patients.

Srijana Adhikari,1 Ruth Marie Antoinette van Nispen,2 Ellen Bernadette Maria Elsman,2 Fleur van Rens,3 Ger van Rens2 1Department of Pediatric Ophthalmology and Strabismus, Tilganga Institute of Ophthalmology, Kathmandu, Nepal; 2Department of Ophthalmology, VU University Medical Centre and the Amsterdam Public Health Research Institute, Amsterdam, the Netherlands; 3Discipline of Exercise Science, Murdoch University, Murdoch, WA, AustraliaCorrespondence: Srijana Adhikari, Tilganga Institute of Ophthalmology, Gaushala, PO Box 561, Kathmandu, Nepal, Tel +977-9849287387, Email srij_a@yahoo.comPurpose: To study the causes of moderate and severe visual impairment (VI) and blindness and its changing trends in Nepalese children.Patients and Methods: A cross-sectional descriptive study was conducted. Participants, aged 7 to 17 years were recruited from integrated schools for the blind and the outpatient department of a tertiary eye hospital in Kathmandu. VI and blindness were categorized according to World Health Organization (WHO) categories and its protocol for eye examination of children with blindness and VI was followed. Findings were compared to former studies from Nepal.Results: A total of 200 children were included, of whom 45% had moderate VI, 5% had severe VI, and 50% were blind. Mean age of children with VI and blindness was 11.1 (SD = 3.3) and 12.9 (SD = 3) years, respectively. Forty percent of children with VI and 38% of blind children were female. In our study, retina (39%) and whole globe (32%) were the most common anatomical site of involvement in children with VI and blindness, respectively, while cornea was the most common anatomical site of involvement in former studies. Heredity (43%) was the most common etiological factor although in 24.5% of all children, etiology was unknown. In 43.5% of children, blindness and VI was due to avoidable causes.Conclusion: In relatively many children, the etiology of VI and blindness could be either prevented or treated. Compared to former studies from Nepal, there is a changing trend in the etiology of severe VI and blindness.Keywords: childhood blindness, Nepal, visual impairment, pediatric

Telemonitoring disease activity with electronic patient-reported outcomes (ePROs) may reduce the workload of rheumatic care by decreasing outpatient clinic visits. However, low adherence to reporting ePROs is frequently observed. Our objective was to identify facilitators and barriers to weekly monitoring of disease activity with ePROs. Patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) who recently participated in one of the two telemonitoring studies with ePROs completed in a smartphone app, were invited to participate in focus group discussions (FGD). Thematic analysis was used to identify themes that play a role in the decision to continue or stop reporting weekly ePROs. A total of 22 patients participated in three FGDs. Five themes were identified that were of importance to adhere to telemonitoring: (1) questionnaire frequency, (2) discussing results of completed ePROs, (3) physical consultations, (4) patient insight into disease activity and (5) user experience of the app. All themes contained both barrier and facilitator elements. The results suggest that to improve adherence to telemonitoring of disease activity with ePROs, the perceived benefits of completing ePROs should be maximized. This can be done by providing patients the ability to skip (unneeded) physical consultations in case of low disease activity, and training clinicians to always discuss the completed ePROs. In addition, it is essential to reduce the effort to report ePROs, by tailoring the frequency of ePROs based on the patients’ disease activity or preference, aiming for optimal app functionality as well as by sending notifications when new ePROs are available.

Introduction: Since the eight edition of the Union for In-ternational Cancer Control and American Joint Committee on Cancer TNM classification system, the primary tumor pT stage is determined on the basis of presence and size of the invasive components. The aim of this study was to identify histologic features in tumors with lepidic growth pattern which may be used to establish criteria for distinguishing invasive from noninvasive areas.Methods: A Delphi approach was used with two rounds of blinded anonymized analysis of resected nonmucinous lung adenocarcinoma cases with presumed invasive and nonin-vasive components, followed by one round of reviewer de-anonymized and unblinded review of cases with known outcomes. A digital pathology platform was used for measuring total tumor size and invasive tumor size. Results: The mean coefficient of variation for measuring total tumor size and tumor invasive size was 6.9% (range: 1.7%-22.3%) and 54% (range: 14.7%-155%), respectively, with substantial variations in interpretation of the size and location of invasion among pathologists. Following the presentation of the results and further discussion among members at large of the International Association for the Study of Lung Cancer Pathology Committee, extensive epithelial proliferation (EEP) in areas of collapsed lepidic growth pattern is recognized as a feature likely to be associated with invasive growth. The EEP is characterized by multilayered luminal epithelial cell growth, usually with high-grade cytologic features in several alveolar spaces.Conclusions: Collapsed alveoli and transition zones with EEP were identified by the Delphi process as morphologic features that were a source of interobserver variability. Definition criteria for collapse and EEP are proposed to improve reproducibility of invasion measurement.(c) 2022 International Association for the Study of Lung Cancer.

Background: Ethnic minority groups experience a disproportionately high burden of infections, hospitalizations and mortality due to COVID-19, and therefore should be especially encouraged to receive SARS-CoV-2 vaccination. This study aimed to investigate the intent to vaccinate against SARS-CoV-2, along with its determinants, in six ethnic groups residing in Amsterdam, the Netherlands. Methods: We analyzed data of participants enrolled in the population-based multi-ethnic HELIUS cohort, aged 24 to 79 years, who were tested for SARS-CoV-2 antibodies and answered questions on vaccination intent from November 23, 2020 to March 31, 2021. During the study period, SARS-CoV-2 vaccination in the Netherlands became available to individuals working in healthcare or > 75 years old. Vaccination intent was measured by two statements on a 7-point Likert scale and categorized into low, medium, and high. Using ordinal logistic regression, we examined the association between ethnicity and lower vaccination intent. We also assessed determinants of lower vaccination intent per ethnic group. Results: A total of 2,068 participants were included (median age 56 years, interquartile range 46–63). High intent to vaccinate was most common in the Dutch ethnic origin group (369/466, 79.2%), followed by the Ghanaian (111/213, 52.1%), South-Asian Surinamese (186/391, 47.6%), Turkish (153/325, 47.1%), African Surinamese (156/362, 43.1%), and Moroccan ethnic groups (92/311, 29.6%). Lower intent to vaccinate was more common in all groups other than the Dutch group (P < 0.001). Being female, believing that COVID-19 is exaggerated in the media, and being < 45 years of age were common determinants of lower SARS-CoV-2 vaccination intent across most ethnic groups. Other identified determinants were specific to certain ethnic groups. Conclusions: Lower intent to vaccinate against SARS-CoV-2 in the largest ethnic minority groups of Amsterdam is a major public health concern. The ethnic-specific and general determinants of lower vaccination intent observed in this study could help shape vaccination interventions and campaigns.

Aim: To investigate the interplay of incident chronic kidney disease (CKD) and/or heart failure (HF) and their associations with prognosis in a large, population-based cohort with type 2 diabetes (T2DM).Methods: Patients aged ≥18 years with new-onset T2DM, without renal disease or HF at baseline, were identified from the territory-wide Clinical Data Analysis Reporting System between 2000 and 2015. Patients were followed up until December 31, 2020 for incident CKD and/or HF and all-cause mortality.Results: Among 102 488 patients (median age 66 years, 45.7% women, median follow-up 7.5 years), new-onset CKD occurred in 14 798 patients (14.4%), in whom 21.7% had HF. In contrast, among 9258 patients (9.0%) with new-onset HF, 34.6% had CKD. The median time from baseline to incident CKD or HF (4.4 vs. 4.1 years) did not differ. However, the median (interquartile range) time until incident HF after CKD diagnosis was 1.7 (0.5-3.6) years and was 1.2 (0.2-3.4) years for incident CKD after HF diagnosis (P < 0.001). The crude incidence of CKD was higher than that of HF: 17.6 (95% confidence interval [CI] 17.3-17.9) vs. 10.6 (95% CI 10.4-10.9)/1000 person-years, respectively, but incident HF was associated with a higher adjusted-mortality than incident CKD. The presence of either condition (vs. CKD/HF-free status) was associated with a three-fold hazard of death, whereas concomitant HF and CKD conferred a six to seven-fold adjusted hazard of mortality.Conclusion: Cardiorenal complications are common and are associated with high mortality risk among patients with new-onset T2DM. Close surveillance of these dual complications is crucial to reduce the burden of disease.

STUDY OBJECTIVES: We investigated the prevalence of self-reported insomnia symptoms in people with type 2 diabetes and assessed the association with metabolic outcomes and the mediating role of lifestyle factors. METHODS: In a prospective cohort of 1,272 participants with type 2 diabetes (63.4% male, age 68.7 ± 9 years) we measured insomnia symptoms using the Insomnia Severity Index and metabolic outcomes as hemoglobin A1c, glucose, lipids, and body mass index at baseline and at 1 year follow-up. Linear regression analyses assessed the association between insomnia symptoms and metabolic outcomes, corrected for demographic factors, comorbidities, and body mass index. Mediation analyses were conducted for lifestyle factors. RESULTS: The prevalence of mild and severe insomnia symptoms was 23.0% and 10.7%, respectively. When adjusted for demographic factors and comorbidities, cross-sectionally severe insomnia symptoms were associated with higher body mass index (β = 0.97 kg/m2; 95% confidence interval 0.04: 1.89) compared to no insomnia symptoms. Cross-sectionally, no associations were observed for the other metabolic outcomes. Additionally, no prospective associations were observed with any of the outcomes. Finally, physical activity mediated the association between severe insomnia symptoms and body mass index by 29.3%. CONCLUSIONS: About a third of people with type 2 diabetes experience self-reported insomnia symptoms, but insomnia symptoms were not associated with metabolic outcomes in people with type 2 diabetes. CITATION: Groeneveld L, den Braver NR, Beulens JWJ, et al. The prevalence of self-reported insomnia symptoms and association with metabolic outcomes in people with type 2 diabetes: the Hoorn Diabetes Care System cohort. J Clin Sleep Med. 2023;19(3):539-548.

Background: The WHO recommends soda taxes to reduce sugar consumption, but the effect across socioeconomic groups is unclear. Objectives: We assessed 16-y trends in daily soda consumption among adolescents in 4 European countries with a soda tax and 5 comparison countries, by family affluence. Methods: Five rounds of the international “Health Behaviour in School-Aged Children” school-based survey were used (school years 2001/2002 to 2017/2018, repeated cross-sectional design). Finland, France, Belgium, and Portugal introduced or updated a soda tax during this period. For comparison, we selected 5 neighboring countries without such a tax. Nationally representative samples of adolescents aged 13 and 15 y (n = 165,521; 51.2% girls) completed a standardized questionnaire, including a question on soda consumption frequency. Using the family affluence scale (FAS), we categorized adolescents into lower-, middle- or higher-affluent groups. Changes in daily soda consumption were assessed in each country independently. Results: Before taxation, daily soda consumption was more likely among lower-affluent adolescents in France and Belgium (P < 0.001, socioeconomic inequalities) and was similar across FAS groups in Finland and Portugal (no inequalities). After the tax, daily soda consumption was reduced across all FAS groups in Finland, Belgium, and Portugal (P interactions ≥ 0.33). In France, a posttax decrease was observed only among lower-affluent adolescents (OR lower, 0.76; 95% CI: 0.60, 0.96; reduced inequalities). During the same periods, socioeconomic patterns remained stable in 3 comparison countries (P interactions ≥ 0.38), and larger reductions in daily soda consumption were observed among middle- or higher-affluent adolescents compared with lower-affluent adolescents in the remaining 2 comparison countries (P interactions ≤ 0.08, increased inequalities). Conclusions: Socioeconomic patterns did not change after the tax implementation in 3 out of 4 countries, and socioeconomic inequalities were reduced in France. Taxing sodas might be an effective measure to attenuate, or at least not exacerbate, socioeconomic inequalities in adolescent daily soda consumption. Am J Clin Nutr 20XX;xx:xx–xx.