This study aimed to develop a vancomycin population pharmacokinetic model in obese adult patients treated with intermittent haemodialysis and propose a model-based loading dose strategy ensuring attainment of newly recommended AUC-based PK/PD target. Retrospective cross-sectional analysis was performed among obese haemodialysis dependent adult patients treated with intravenous vancomycin. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were used to identify the optimal loading dose for PK/PD target attainment during the first 48 h of treatment. Therapeutic drug monitoring data from 27 patients with a BMI of 30.2-52.9 kg/m2 were analysed. Among all tested variables, only LBM as a covariate of vancomycin Vd significantly improved the model, while vancomycin CL did not correlate with any of the tested variables. The median (IQR) value from the conditional mean of individual estimates of Vd and CL was 68.4 (56.6-84.2) L and 0.86 (0.79-0.90) L/h, respectively. To ensure optimal vancomycin exposure during the first 48 h of therapy, the vancomycin loading dose of 1500, 1750, 2000, 2250, 2500 and 2750 mg should be administered to obese patients with a lean body mass of ˂50, 50-60, 60-70, 70-80, 80-85 and >85 kg, respectively.

• MeSH
• Anti-Bacterial Agents * pharmacokinetics   administration & dosage   MeSH
• Models, Biological MeSH
• Renal Dialysis * MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Monte Carlo Method MeSH
• Drug Monitoring MeSH
• Obesity * complications   MeSH
• Cross-Sectional Studies MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Vancomycin * pharmacokinetics   administration & dosage   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

PURPOSE: A healthy lifestyle may prevent or mitigate late effects in childhood, adolescent and young adult (CAYA) cancer survivors. To support survivors in adopting healthier behaviours, the PanCareFollowUp (PCFU) Lifestyle intervention was developed, encompassing 4 months of online lifestyle coaching aimed at achieving a personal lifestyle goal. The aims of this study were to (1) determine the efficacy of this intervention on lifestyle outcomes over time and (2) identify predictors for goal achievement. PATIENTS AND METHODS: Fifty-eight survivors were enrolled. Outcomes were assessed at baseline (T0), after 4 months of coaching (T1) and after 4 months of follow-up (T2). The primary outcome included the percentage of survivors successful in achieving and sustaining their goal, whereas secondary outcomes included differences in body mass index (BMI), diet and physical activity. To evaluate the adjusted, longitudinal effects on secondary outcomes, linear mixed models were estimated. Predictors for goal achievement were identified through logistic regression analysis. RESULTS: At T1 and T2, 68% and 76% of goals were achieved or sustained, respectively. Mean differences between T2 and T0 showed significant improvements in BMI (-0.5 kg/m2), diet (-0.6 points) and physical activity (+7.7 h/week). Estimation of multivariable models also showed positive effects. Participants with a lower BMI and fewer depressive feelings at baseline were more likely to achieve and/or sustain their goals at T2. CONCLUSION: Findings suggest that the PCFU Lifestyle intervention supports survivors in making lifestyle changes. Results can be used to inform a subsequent randomised intervention study and integrate lifestyle coaching into care. TRIAL REGISTRATION: International Clinical Trial Registry Platform (ICTRP) number: NL8932 (ICTRP Search Portal [who. int]). Registered on 29 September 2020.

• MeSH
• Exercise * MeSH
• Child MeSH
• Adult MeSH
• Body Mass Index MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Neoplasms therapy   psychology   MeSH
• Cancer Survivors * psychology   MeSH
• Telemedicine * MeSH
• Healthy Lifestyle MeSH
• Life Style MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: In our previous study on erythropoiesis-stimulating agent (ESA) treatment in lower risk myelodysplastic syndromes from the European MDS (EUMDS) Registry, we showed that patients treated with ESAs had longer survival compared with patients who receive red blood cell transfusion (RBCT). In this study, with a longer follow up time and more patients included, we aimed to assess long-term effects on survival and health-related quality of life (HRQoL) of exposure to ESAs with or without RBCT in patients with lower risk myelodysplastic syndromes. METHODS: The EUMDS Registry is a non-interventional, longitudinal, real-world registry prospectively enrolling newly diagnosed patients older than 18 years with lower risk (International Prognostic Scoring System low or intermediate-1) myelodysplastic syndromes from 16 European countries and Israel. The analysis was restricted to patients with haemoglobin concentrations less than 100 g/L enrolled between Jan 1, 2008, and July 1, 2019, with last censoring of data on Dec 31, 2021. Patient management was recorded every 6 months, including treatment, transfusions, and HRQoL. ESA treatment followed local guidelines. The patients were separated into four groups at each study visit: no ESA or RBCT, ESA only, ESA plus RBCT, and RBCT only. The data were analysed longitudinally over time according to ESA and RBCT status during each 6-month interval, using propensity score matching. The main outcomes were median overall survival and leukaemia-free survival, and HRQoL. This study is registered with ClinicalTrials.gov, NCT00600860, as is ongoing. FINDINGS: 2448 patients (the ESA-unexposed group [n=1265] and ESA-exposed group [n=1183]) were diagnosed before July 1, 2019; 1520 (62·1%) were male and 928 (37·9%) were female. Median follow-up time was 3·9 years (IQR 1·6-6·5). After applying eligibility criteria and propensity matching, there were 426 patients in the ESA-unexposed group and 744 patients in the ESA-exposed group. Median overall survival in the ESA exposed group was 44·9 months (95% CI 40·2-50·5) compared with 34·8 months (28·6-39·2) in the ESA unexposed group; the absolute difference was 10·1 months (95% CI 2·2-18·0; hazard ratio [HR] 0·70 [95% CI 0·59-0·83]; p<0·0001). Patients without RBCT in the presence or absence of ESA exposure maintained significantly better HRQoL than those with RBCT, irrespective of ESA exposure (linear mixed effect model of EQ-5d-3L index score, RBCT coefficient -0·04 [95% CI -0·06 to 0·03], p<0·0001; linear mixed effect model of VAS, -4·57 [-6·02 to -3·13], p<0·0001). INTERPRETATION: ESA treatment in patients with lower risk myelodysplastic syndromes significantly improves overall survival when started before or early after the onset of regular transfusion therapy. Avoiding RBCT is associated with significantly better HRQoL. FUNDING: H2020 European Research Council, Novartis Pharmacy B V Oncology Europe, Amgen, BMS/Celgene International, Janssen Pharmaceutica, Takeda Pharmaceuticals International, and Gilead Sciences.

• MeSH
• Hematinics * therapeutic use   MeSH
• Cohort Studies MeSH
• Quality of Life * MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Myelodysplastic Syndromes * drug therapy   mortality   therapy   complications   MeSH
• Registries MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Erythrocyte Transfusion adverse effects   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH

OBJECTIVES: This study examined the association between childhood adversity and late-life cognitive outcomes among older Puerto Rican adults. METHODS: Data were from the Puerto Rican Elder: Health Conditions study, a population-based cohort of 3,713 older Puerto Rican adults (mean age 72.5 years; 60% female). Adverse childhood experiences were categorized into four factors: economic hardship, parental illiteracy, childhood illness, and neighborhood disadvantage. Cognition was assessed with the Mini-Mental Cabán (MMC). For our analyses, cognitive impairment was defined as scoring 1.5 standard deviations below the expected score, adjusted for age, sex, education, and reading ability. Ordinal logistic regression (baseline) and generalized linear mixed models (all 3 waves) analyzed MMC scores; generalized estimating equations assessed incident cognitive impairment (Waves 2 and 3). RESULTS: All four adversity factors were associated with poorer MMC scores at baseline. Parental illiteracy (β = -0.35, p < .001) and neighborhood disadvantage (β = -0.27, p < .001) showed stronger associations than economic hardship (β = -0.10, p = .003) and childhood illness (β = -0.21, p < .001). No factors were significantly related to changes in cognitive scores over time. Depressive symptoms and self-rated health partially mediated cross-sectional relationships, with depressive symptoms showing a stronger effect. All adversity factors except economic hardship were linked to baseline cognitive impairment (OR = 1.42 parent illiteracy, OR = 1.24 childhood illness, OR = 1.82 neighborhood disadvantage, p < .05). Only neighborhood disadvantage was associated with incident cognitive impairment (OR = 1.19, p = .003). DISCUSSION: This study highlights the lasting effect of childhood adversity on late-life cognitive health among older Puerto Ricans, suggesting that addressing early adversity may promote cognitive health later in life.

• MeSH
• Neighborhood Characteristics MeSH
• Poverty statistics & numerical data   psychology   MeSH
• Literacy statistics & numerical data   MeSH
• Cognitive Dysfunction * epidemiology   ethnology   etiology   MeSH
• Humans MeSH
• Adverse Childhood Experiences * statistics & numerical data   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Puerto Rico MeSH

BACKGROUND: To design effective tailored interventions to promote physical activity (PA) among older adults, insights are needed into the contexts in which older adults engage in PA and their affective and physical experiences. Sensor-triggered event-based ecological momentary assessment (EMA) is an innovative method for capturing real-life contexts, as well as affective and physical states, during or immediately after specific events, such as PA. This study aimed to (1) describe the physical and social contexts, and the affective and physical states during PA among older adults, (2) evaluate how these constructs fluctuate during PA episodes, and (3) describe affective states during PA according to the context. METHODS: An intensive longitudinal sensor-triggered event-based EMA study was conducted with 92 Belgian older adults (65 + years). During seven days, participants were monitored using a Fitbit, which triggered a smartphone-based questionnaire on the event-based EMA platform 'HealthReact' after a five-minute walk. Participants reported on contexts and affective (positive/negative valence) and physical states (pain and fatigue) during the PA event. Descriptive statistics and generalized mixed models were used for data analysis. RESULTS: Older adults predominantly engaged in daily physical activities, such as walking for transport, leisure walking, and gardening, rather than structured exercise. They consistently reported high positive affect, low negative affect, and minimal physical complaints during PA. Furthermore, older adults mainly engage in physical activities alone, particularly in outdoor settings. Variations in contexts, affect, and fatigue were mostly driven by within-subject differences. The model showed significant differences across times of day, with negative affect being highest in the evening and fatigue lowest in the morning. Additionally, the physical and social context influenced negative affect (but not positive affect), with outdoor activities performed alone and indoor activities performed with others being associated with lower negative affect. CONCLUSIONS: While these findings could enhance the effectiveness of tailored PA interventions, it remains unclear whether the observed affective and physical states are causes or effects of PA, and whether the contexts in which the activities were performed align with older adults' preferences. Further research is needed to explore these relationships and to better understand older adults' preferred PA contexts.

• MeSH
• Affect * MeSH
• Walking MeSH
• Smartphone MeSH
• Exercise * psychology   MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Ecological Momentary Assessment * MeSH
• Surveys and Questionnaires MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Fatigue MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Belgium MeSH

The cerebellum, a lateralised organ, plays a crucial role in motor control. Still, its involvement in hand and foot dominance remains inadequately understood, primarily in the right and left-side dominant population. A potential manifestation of this lateralisation is the neocerebellar extinction syndrome, previously linked to mild muscle hypotonia and moderate passivity in the non-preferred hand. A more precise understanding of the cerebellum's role in limb dominance patterns could provide valuable insights into motor learning, rehabilitation therapies, and neuroplasticity. This study explored the relationship between physiological neocerebellar extinction syndrome and hand/ft dominance in left and right-side dominant individuals. Data were collected from 80 university participants (40 left-side dominant, 40 right-side dominant, mean age = 24.7 ± 0.92 years) during controlled limb falls using 3D kinematic analysis. In these falls, theoretically suggested hypotonia in non-dominant limbs was analysed through attenuation coefficients and frequency differences. Using a linear mixed model, we found significantly lower hand attenuation in the non-dominant hand-(β = 0.10, p < 0.001), showing hypotonia compared to the dominant hand regardless of upper limb side dominance. Foot preference and dominance had minimal influence on leg attenuation or frequency, although right-footed, right-dominant individuals demonstrated significantly higher leg oscillation frequency, likely due to increased proximal muscle mass. Our findings suggest that distinct differences in cortical representation, lateralised control, and pathway specialisation exist due to the unique demands of each limb's motor functions, which are pronounced more neocerebellar extinction syndrome in the upper extremities. Therefore, the results showed potentially new perspectives on the cerebellum's nuanced role in motor control and laterality. The differential effects observed between the upper and lower limbs point to distinct cerebellar pathways and hypotonia. This work could significantly enhance the precision of therapeutic approaches and broaden our knowledge of laterality in motor function.

• MeSH
• Biomechanical Phenomena MeSH
• Adult MeSH
• Functional Laterality * physiology   MeSH
• Humans MeSH
• Young Adult MeSH
• Cerebellum * physiopathology   MeSH
• Foot physiology   MeSH
• Hand MeSH
• Muscle Hypotonia physiopathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Efficacy of tumour necrosis factor inhibitors (TNFi) for peripheral arthritis in patients with psoriatic arthritis (PsA) has been established in randomized clinical trials that have used improvement in summated joint counts as an outcome. Whether joints at different anatomical locations might respond differentially to TNFi remains unknown. The aim of the study was to investigate potential variations in the responsiveness to a first tumour necrosis factor inhibitor (TNFi) among joints at distinct locations in patients with psoriatic arthritis (PsA) treated in routine clinical care. METHODS: Bionaive PsA patients from nine European countries were included in this observational cohort study if ≥ 1 joint was swollen at the initiation of a first TNFi as monotherapy or added to methotrexate. Only the 28-joint count was available without imaging data confirming the presence of synovitis. The primary outcome was time to first resolution of joint swelling at each joint level. Hazard ratios (HR) for resolution comparing different joint locations were estimated using interval-censored mixed-effects Cox proportional hazards models, including a random effect for country and patient, adjusted for age and sex. RESULTS: A total of 1729 patients with 8397 swollen joints at the start of TNFi were included. Considering the upper extremity, a higher rate of resolution of joint swelling (HR, 95% CI) was observed for the shoulder (1.65, 1.16-2.35) and elbow (1.90, 1.38-2.61), while a lower rate was found for the wrist (0.72, 0.62-0.83) compared to the joints of digit 3. Within fingers, and using the same reference, joint swelling resolved fastest in digit 4 (1.77, 1.49-2.11) and digit 5 (1.88, 1.53-2.31). A lower rate of resolution of joint swelling was found for the knee in comparison to the elbow, the corresponding joint on the upper limb (0.56, 0.40-0.78). CONCLUSION: The time to resolution of joint swelling upon treatment with TNFi in patients with PsA seems to depend on the localisation of the affected joints.

• MeSH
• Antirheumatic Agents * therapeutic use   MeSH
• Adult MeSH
• Tumor Necrosis Factor Inhibitors therapeutic use   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Arthritis, Psoriatic * drug therapy   MeSH
• Registries * MeSH
• Aged MeSH
• Tumor Necrosis Factor-alpha antagonists & inhibitors   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH
• Geographicals
• Europe MeSH

STUDY OBJECTIVES: To assess the impact of the non-respiratory arousal burden at baseline polysomnography (PSG) on residual daytime sleepiness in positive airway pressure (PAP)-treated obstructive sleep apnea (OSA). METHODS: We included OSA patients from the European Sleep Apnea Database registry with available arousal data who had at least 2 treatment follow-up visits. The primary outcome was the Epworth Sleepiness Scale (ESS) score under PAP. The non-respiratory arousal ratio (NRAR) was defined as the ratio of non-respiratory to total arousals at baseline PSG. A linear mixed model tested the effect of NRAR tertiles on residual sleepiness. Baseline variables that differed significantly between groups were included as covariates. RESULTS: 800 patients with OSA (69.6 % male, mean age 57.1 ± 12.0 years, mean NRAR 0.22 ± 0.20) were evaluated during three follow up visits at a mean of 197.4, 499.3, and 731.6 days after PAP initiation. The interaction between time and NRAR tertile was statistically significant (F = 4.55, p = 0.001). The lowest NRAR tertile was associated with lower residual sleepiness over time compared to the highest NRAR tertile. The associations were independent of sex, comorbidities, body mass index, blood pressure, baseline apnea-hypopnea index, and baseline ESS score. CONCLUSIONS: NRAR at baseline PSG predicts residual sleepiness in PAP-treated OSA patients. The findings offer new insights into OSA phenotyping and have important implications for patient care.

• MeSH
• Arousal * physiology   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Sleep Apnea, Obstructive * therapy   physiopathology   complications   MeSH
• Polysomnography * MeSH
• Disorders of Excessive Somnolence physiopathology   MeSH
• Registries * MeSH
• Aged MeSH
• Sleepiness MeSH
• Continuous Positive Airway Pressure * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH

PURPOSE: With the increasing use of proton therapy, there is a growing emphasis on including radiation quality, often quantified by linear energy transfer, as a treatment plan optimization factor. The Timepix detectors offer energy-sensitive particle tracking useful for the characterization of proton linear energy transfer. To improve the detector's performance in mixed radiation fields produced in proton therapy, we customized the detector settings and performed the per-pixel energy calibration. METHODS: The detection threshold and per-pixel signal shaping time (IKrum current) were customized, and energy calibration was performed for MiniPIX Timepix3. The detector calibration was verified using α source and clinical proton beams, as well as Monte Carlo simulations. The effects on the detector's performance, in terms of spectral saturation and pixel occupancy, were evaluated. RESULTS: Measurements with proton beams showed a good agreement with simulations. With the customized settings, the measurable energy range in the detector data-driven mode was extended, and the signal duration time was reduced by 80%, while the yield of pixel time occupancy reduction depends on the number of occupied pixels. For performed measurements with proton beams, the number of occupied pixels was further reduced up to 40% due to the increased threshold. CONCLUSIONS: Customized detector configuration of the Timepix3 detector allowed for reduced pixel occupancy and mitigation of signal saturation in a data-driven mode without significantly interfering with the energy deposition measurement. The presented approach enables the extension of the operational range, including higher intensities and mixed-radiation fields in particle radiotherapy environments.

• MeSH
• Calibration MeSH
• Linear Energy Transfer MeSH
• Monte Carlo Method * MeSH
• Proton Therapy * instrumentation   MeSH
• Publication type
• Journal Article MeSH

OBJECTIVES: Research questions about how and why health trends differ between populations require decisions about data analytic procedure. The objective was to document and compare the information returned from stratified, fixed effect and random effect approaches to data modelling for two prototypical descriptive research questions about comparative trends in toothbrushing. METHODS: Data included five cycles of the Health Behaviour in School-aged Children 2006 to 2022, which provided a sample of 980192 11- to 15- year olds from 35 countries. Using logistic regression models and generalized linear mixed models, toothbrushing daily was regressed on time, following the three approaches to analysis of trends. RESULTS: The stratified approach suggested a positive but non-linear trend in toothbrushing from 2006 to 2022 in most countries but provided no statistical inference on the variation. The fixed effect and the random effect approach converged on a positive but flattening overall trend, with a statistically significant country variation in trends. CONCLUSION: Only the fixed effect approach and the random effects approach provided clear answers to the research question. Additional methodological considerations for making an informed choice of analytical approach are discussed.

• MeSH
• Adolescent Behavior MeSH
• Toothbrushing * statistics & numerical data   trends   MeSH
• Child MeSH
• Humans MeSH
• Logistic Models MeSH
• Adolescent MeSH
• Health Behavior MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH