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BACKGROUND: Severe depression is associated with accelerated brain aging. BrainAge gap, the difference between predicted and observed BrainAge was investigated in patients with late-life depression (LLD). We aimed to examine BrainAge gap in LLD and its associations with clinical characteristics indexing LLD chronicity, current severity, prior to electroconvulsive therapy (ECT) and ECT outcome. METHODS: Data was analyzed from the Mood Disorders in Elderly treated with Electroconvulsive Therapy (MODECT) study. A previously established BrainAge algorithm (BrainAge R by James Cole, (https://github.com/james-cole/brainageR)) was applied to pre-ECT T1-weighted structural MRI-scans of 42 patients who underwent ECT. RESULTS: A BrainAge gap of 1.8 years (SD = 5.5) was observed, Cohen's d = 0.3. No significant associations between BrainAge gap, number of previous episodes, current episode duration, age of onset, depression severity, psychotic symptoms or ECT outcome were observed. LIMITATIONS: Limited sample size. CONCLUSIONS: Our initial findings suggest an older BrainAge than chronological age in patients with severe LLD referred for ECT, however with high degree of variability and direction of the gap. No associations were found with clinical measures. Larger samples including are needed to better understand brain aging and to evaluate the usability of BrainAge gap as potential biomarker of prognosis an treatment-response in LLD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02667353.

Objectives: To illustrate in-depth validation of prediction models developed on multicenter data. Methods: For each hospital in a multicenter registry, we evaluated predictive performance of a 30-day mortality prediction model for transcatheter aortic valve implantation (TAVI) using the Netherlands heart registration (NHR) dataset. We measured discrimination and calibration per hospital in a leave-center-out analysis (LCOA). Meta-analysis was used to calculate I2 values per performance metric from the LCOA and to compute mean and confidence interval (CI) estimates. Case mix differences between studies were inspected using the framework of Debray et al. for understanding external validation. We also aimed to discover subgroups (SGs) with high model prediction error (PE) and their distribution over the centers. Results: We studied 16 hospitals with 11,599 TAVI patients with an early mortality of 3.7%. The models’ area under the curve (AUCs) had a wide range between hospitals from 0.59 to 0.79, and miscalibration occurred in seven hospitals. Mean AUC from meta-analysis was 0.68 (95% CI 0.65-0.70). I2 values were 0%, 74%, and 0% for AUC, calibration intercept and slope, respectively. Between-hospital case-mix differences were substantial, and model transportability was low. One SG was discovered with marked global PE and was associated with poor performance on validation centers. Conclusion: The illustrated combination of approaches provides useful insights to inspect multicenter-based prediction models, and it exposes their limitations in transportability and performance variability when applied to different populations.

Background: The impact of pulmonary valve replacement (PVR) on major adverse clinical outcomes in patients with repaired tetralogy of Fallot (rTOF) is unknown. Objectives: The purpose of this study was to determine whether PVR is associated with improved survival and freedom from sustained ventricular tachycardia (VT) in rTOF. Methods: A PVR propensity score was created to adjust for baseline differences between PVR and non-PVR patients enrolled in INDICATOR (International Multicenter TOF Registry). The primary outcome was time to the earliest occurrence of death or sustained VT. PVR and non-PVR patients were matched 1:1 on PVR propensity score (matched cohort) and in the full cohort, modeling was performed with propensity score as a covariate adjustment. Results: Among 1,143 patients with rTOF (age 27 ± 14 years, 47% PVR, follow-up 8.3 ± 5.2 years), the primary outcome occurred in 82. The adjusted HR for the primary outcome for PVR vs no-PVR (matched cohort n = 524) was 0.41 (95% CI: 0.21-0.81; multivariable model P = 0.010). Full cohort analysis revealed similar results. Subgroup analysis suggested beneficial effects in patients with advanced right ventricular (RV) dilatation (interaction P = 0.046; full cohort). In patients with RV end-systolic volume index >80 mL/m2, PVR was associated with a lower primary outcome risk (HR: 0.32; 95% CI: 0.16-0.62; P < 0.001). There was no association between PVR and the primary outcome in patients with RV end-systolic volume index ≤80 mL/m2 (HR: 0.86; 95% CI: 0.38-1.92; P = 0.70). Conclusions: Compared with rTOF patients who did not receive PVR, propensity score-matched individuals receiving PVR had lower risk of a composite endpoint of death or sustained VT.

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.

Biological aging of human organ systems reflects the interplay of age, chronic disease, lifestyle and genetic risk. Using longitudinal brain imaging and physiological phenotypes from the UK Biobank, we establish normative models of biological age for three brain and seven body systems. Here we find that an organ’s biological age selectively influences the aging of other organ systems, revealing a multiorgan aging network. We report organ age profiles for 16 chronic diseases, where advanced biological aging extends from the organ of primary disease to multiple systems. Advanced body age associates with several lifestyle and environmental factors, leukocyte telomere lengths and mortality risk, and predicts survival time (area under the curve of 0.77) and premature death (area under the curve of 0.86). Our work reveals the multisystem nature of human aging in health and chronic disease. It may enable early identification of individuals at increased risk of aging-related morbidity and inform new strategies to potentially limit organ-specific aging in such individuals.

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

Background:Patient-reported outcome measures such as the Oxford Hip Score (OHS) can capture patient-centered perspectives on outcomes after total hip arthroplasty (THA). The OHS assesses hip pain and functional limitations, but defining interpretation threshold values for the OHS is warranted so that numerical OHS values can be translated into whether patients have experienced clinically meaningful changes. Therefore, we determined the minimal important change (MIC), patient acceptable symptom state (PASS), and treatment failure (TF) threshold values for the OHS at 12 and 24-month follow-up in patients undergoing THA. Methods:This cohort study used data from patients undergoing THA at 1 public hospital between July 2016 and April 2021. At 12 and 24 months postoperatively, patients provided responses for the OHS and for 3 anchor questions about whether they had experienced changes in hip pain and function, whether they considered their symptom state to be satisfactory, and if it was not satisfactory, whether they considered the treatment to have failed. The anchor-based adjusted predictive modeling method was used to determine interpretation threshold values. Baseline dependency was evaluated using a new item-split method. Nonparametric bootstrapping was used to determine 95% confidence intervals (CIs). Results:Complete data were obtained for 706 (69%) of 1,027 and 728 (66%) of 1,101 patients at 12 and 24 months postoperatively, respectively. These patients had a median age of 70 years, and 55% to 56% were female. Adjusted OHS MIC values were 6.3 (CI, 4.6 to 8.1) and 5.2 (CI, 3.6 to 6.7), adjusted OHS PASS values were 30.6 (CI, 29.0 to 32.2) and 30.5 (CI, 29.3 to 31.8), and adjusted OHS TF values were 25.5 (CI, 22.9 to 27.7) and 27.0 (CI, 25.2 to 28.8) at 12 and 24 months postoperatively, respectively. MIC values were 5.4 (CI, 2.1 to 9.1) and 5.0 (CI, 1.9 to 8.7) higher at 12 and 24 months, respectively, in patients with a more severe preoperative state. Conclusions:The established interpretation threshold values advance the interpretation and clinical use of the OHS, and may prove especially beneficial for registry-based evaluations of treatment quality. Level of Evidence:PrognosticLevel IV. See Instructions for Authors for a complete description of levels of evidence.

Background: The safety and effectiveness of rivaroxaban versus vitamin K antagonists (standard of care [SOC]) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) was evaluated in Europe. Research design and methods: Observational studies were conducted in the UK, the Netherlands, Germany, and Sweden. Primary safety outcomes were hospitalization for intracranial hemorrhage, gastrointestinal bleeding, or urogenital bleeding among new users of rivaroxaban and SOC with NVAF; outcomes were analyzed using cohort (rivaroxaban or SOC use) and nested case–control designs (current vs nonuse). Statistical analyses comparing rivaroxaban and SOC cohorts were not performed. Results: Overall, 162,919 rivaroxaban users and 177,758 SOC users were identified. In the cohort analysis, incidence ranges for rivaroxaban users were 0.25–0.63 events per 100 person-years for intracranial bleeding, 0.49–1.72 for gastrointestinal bleeding, and 0.27–0.54 for urogenital bleeding. Corresponding ranges for SOC users were 0.30–0.80, 0.30–1.42, and 0.24–0.42, respectively. In the nested case–control analysis, current SOC use generally presented a greater risk of bleeding outcomes than nonuse. Rivaroxaban use (vs nonuse) was associated with a higher risk of gastrointestinal bleeding, but a similar risk of intracranial or urogenital bleeding, in most countries. Ischemic stroke incidence ranged from 0.31 to 1.52 events per 100 person-years for rivaroxaban users. Conclusions: Incidences of intracranial bleeding were generally lower with rivaroxaban than with SOC, whereas incidences of gastrointestinal and urogenital bleeding were generally higher. The safety profile of rivaroxaban for NVAF in routine practice is consistent with findings from randomized controlled trials and other studies.

The term “psychologically informed health care” refers to the comprehensive integration of psychological principles into health care. Psychologically informed health care has the potential to lead to a transformation of care, resulting in truly transdisciplinary care. To facilitate its future development, we discuss key characteristics of this approach. These include the direct mode (psychologists assessing and treating patients themselves) and indirect mode (psychologists working through other health care providers) of integrating psychological principles into healthcare; the range of health domains targeted using this approach; transdisciplinary care, transcending traditional disciplinary boundaries; and the positioning of care. We describe a framework for transdisciplinary care, which we refer to as the Framework for Catalytic Collaboration. This framework comprises six dimensions: setting, disciplines, patients/clients, mode of psychological care, primary components of care, and primary targets of care. We also provide four brief illustrations of psychologically informed health care. Finally, we discuss future directions, including the need for professional recognition of the indirect mode, financing of the indirect mode, cross-disciplinary training and trans-disciplinary research.

Postoperative neurocognitive disorders occur frequently in older adult patients. Neuropsychological assessment is the gold standard for diagnosis, but the resources required for routine use are significant. Instead, it is common for simplified and unvalidated tests to be used for trials and in clinical practice. We undertook a single-centre prospective observational study in elective surgical patients aged ? 65 years recruited between September 2019 and January 2021. Patients underwent neuropsychological assessment, the Modified Telephone Interview for Cognitive Status and Montreal Cognitive Assessment before surgery. Tests were repeated at approximately four to eight postoperative weeks. We included 105 patients and 28 (27%) were lost to follow-up. Pre-operative Modified Telephone Interview for Cognitive Status and cognitive domain scores were very weakly to moderately correlated (r?=?0.09?0.41). Pre-operative Montreal Cognitive Assessment and cognitive domain scores were very weakly to weakly correlated (r?=?0.17?0.37) Postoperative Modified Telephone Interview for Cognitive Status and cognitive domain scores were very weakly to weakly correlated (r?=?0.09?0.36). Postoperative Montreal Cognitive Assessment score and cognitive domain scores were very weakly to weakly correlated (r?=?0.07?0.36). Overall, there was limited agreement between tests. We conclude that the Modified Telephone Interview for Cognitive Status and Montreal Cognitive Assessment should not be used in isolation to diagnose postoperative neurocognitive disorders. There seems to be little to no pre-operative, postoperative or pre- to postoperative correlation between these tests and the neuropsychological assessment in older adults without pre-operative cognitive impairment.

Little is known about the safety and surgical outcomes of mastectomy after breast reduction in the trans male population. Several concerns have been voiced that performing mastectomy with prior breast reduction surgery, increases the risk for complications and revision surgery. All transgender men with a history of breast reduction, who underwent a mastectomy at our center between 01-1990 and 01-2021 were identified from our hospital registry. A retrospective chart study was conducted recording surgical characteristics, surgical complications, revision surgery, and clinical follow-up. A total of 1362 subcutaneous mastectomies were performed between 01-1990 and 01-2021. A total of 36 (2.6%) individuals were included (35 bilateral and 1 unilateral breast reduction). The mean age at mastectomy was 37 ? 10 years, and the median time between breast reduction and mastectomy was 6.3 years (range 1.0?31.1). Most individuals underwent a Wise-pattern breast reduction (91%) and a double incision mastectomy with free nipple grafts (86%). Following mastectomy, one acute reoperation was performed because of hemorrhage (3%). Partial pedicled nipple necrosis was seen in 7% and (partial) non-take of nipple grafts in 4%. Scar revisions were performed in 9%, dogear corrections in 20%, and both nipple corrections, and contour corrections in 6%. When comparing the outcomes in literature for surgical complications, scar revision, contour correction or nipple areolar complex revision, no clear disadvantage seems to be present when performing mastectomy after breast reduction. Mastectomy is a safe procedure in transgender men with a history of breast reduction.

BACKGROUND Since the birth of the first baby using IVF technology in 1978, over 10 million children have been conceived via ART. Although most aspects of ARTs were developed in animal models, the introduction of these technologies into clinical practice was performed without comprehensive assessment of their long-term safety. The monitoring of these technologies over time has revealed differences in the physiology of babies produced using ARTs, yet due to the pathology of those presenting for treatment, it is challenging to separate the cause of infertility from the effect of treatments offered. The use of systematic review and meta-analysis to investigate the impacts of the predominant ART interventions used clinically in human populations on animals produced in healthy fertile populations offers an alternative approach to understanding the long-term safety of reproductive technologies. OBJECTIVE AND RATIONALE This systematic review and meta-analysis aimed to examine the evidence available from animal studies on physiological outcomes in the offspring conceived after IVF, IVM or ICSI, compared to in vivo fertilization, and to provide an overview on the landscape of research in this area. SEARCH METHODS PubMed, Embase and Commonwealth Agricultural Bureaux (CAB) Abstracts were searched for relevant studies published until 27 August 2021. Search terms relating to assisted reproductive technology, postnatal outcomes and mammalian animal models were used. Studies that compared postnatal outcomes between in vitro-conceived (IVF, ICSI or IVM) and in vivo-conceived mammalian animal models were included. In vivo conception included mating, artificial insemination, or either of these followed by embryo transfer to a recipient animal with or without in vitro culture. Outcomes included birth weight, gestation length, cardiovascular, metabolic and behavioural characteristics and lifespan. OUTCOMES A total of 61 studies in five different species (bovine, equine, murine, ovine and non-human primate) met the inclusion criteria. The bovine model was the most frequently used in IVM studies (32/40), while the murine model was mostly used in IVF (17/20) and ICSI (6/8) investigations. Despite considerable heterogeneity, these studies suggest that the use of IVF or maturation results in offspring with higher birthweights and a longer length of gestation, with most of this evidence coming from studies in cattle. These techniques may also impair glucose and lipid metabolism in male mice. The findings on cardiovascular outcomes and behaviour outcomes were inconsistent across studies. WIDER IMPLICATIONS Conception via in vitro or in vivo means appears to have an influence on measurable outcomes of offspring physiology, manifesting differently across the species studied. Importantly, it can be noted that these measurable differences are noticeable in healthy, fertile animal populations. Thus, common ART interventions may have long-term consequences for those conceived through these techniques, regardless of the pathology underpinning diagnosed infertility. However, due to heterogeneous methods, results and measured outcomes, highlighted in this review, it is difficult to draw firm conclusions. Optimizing animal and human studies that investigate the safety of new reproductive technologies will provide insight into safeguarding the introduction of novel interventions into the clinical setting. Cautiously prescribing the use of ARTs clinically may also be considered to reduce the chance of promoting adverse outcomes in children conceived before long-term safety is confidently documented.

Introduction: Major depressive disorder (MDD) is a common psychiatric disorder. Despite several treatment options, a subgroup of patients will not respond to the commonly used antidepressant treatments and thus express treatment resistance (TRD). TRD can be quantified with the Dutch Measure for Treatment Resistance in Depression (DM-TRD). Electroconvulsive therapy (ECT) is an effective treatment for MDD, also in TRD. Yet, the position of ECT as “treatment-of-last-resort” may decrease the likelihood of beneficial outcome. Our aim was to investigate the association between treatment resistance and outcome and course of ECT. Methods: We performed a retrospective, multicenter cohort study with 440 patients of which data was retrieved from patient records as collected in the Dutch ECT Cohort database. Linear and logistic regression models were used to explore the association between level of treatment resistance and outcome of ECT. Median split was used to explore the differences between high and low level of TRD and course of treatment. Results: A higher DM-TRD score was associated with significantly smaller reduction of depression symptoms (R 2 = 0.160; β = −2.968; p < 0.001) and lower chance of response (OR = 0.821 [95 CI: 0.760–0.888]; β = −0.197; p < 0.001). Low level TRD patients underwent fewer ECT sessions (mean 13 ± 6 SD vs. 16 ± 7 SD; p < 0.001) and fewer switches from right unilateral tot bifrontotemporal electrode placement (29% vs. 40%; p = 0.032). Conclusion: Reserving ECT as “treatment-of-last-resort” in the treatment algorithm for MDD seems questionable, because in our study lower level of treatment resistance predicted more beneficial ECT-outcome. Moreover, providing ECT in less treatment resistant patients showed fewer needed ECT-sessions and less switches to BL electrode placement, which may decrease the risk for cognitive side-effects.

Contains fulltext : 290880.pdf (Publisher’s version ) (Open Access) Objective: Workers with a lower socioeconomic position (SEP) often face problems on multiple life domains. This study evaluated an intervention to identify and solve problems on multiple life domains, called 'Grip on Health'. Methods: A mixed methods process evaluation was performed among occupational health professionals (OHPs) and lower SEP workers with problems on multiple life domains. Results: Thirteen OHPs delivered the intervention to 27 workers. For seven workers the supervisor was involved, and for two, stakeholders from outside the workplace. Agreements between OHPs with employers often affected implementation. OHPs were essential to help workers identify and solve problems. The intervention increased workers’ health awareness and self-control, and led to small and practical solutions. Conclusions: Grip on Health can support lower SEP workers with solving problems on multiple life domains. However, contextual factors make implementation difficult. 9 p.

Introduction: Postoperative complications following major surgery have been shown to be associated with reduced health-related quality of life (HRQL), and severe complications may have profound negative effects. This study aimed to examine whether long-term HRQL differs with the occurrence and severity of complications in a European multicenter prospective dataset of patients following esophagectomy for cancer. Methods: Disease-free patients following esophagectomy for cancer between 2010 and 2016 from the LASER study were included. Patients completed the LASER, EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires >1 year following treatment. Long-term HRQL was compared between patients with and without postoperative complications, subgroup analysis was performed for severity of complications (no, minor [Clavien-Dindo I-II], severe [Clavien-Dindo ≥ III]), using univariable and multivariable regression. Results: 645 patients were included: 283 patients with no, 207 with minor and 155 with severe complications. Significantly more dyspnea (QLQ-C30) was reported by patients with compared to patients without complications (differenceinmeans 6.3). In subgroup analysis, patients with severe complications reported more dyspnea (difference in means 8.3) than patients with no complications. None of the differences were clinically relevant (difference in means ≥ 10 points). LASER-based low mood (OR2.3) was statistically different for minor versus severe complications. Conclusion: Comparable HRQL was found in patients with and without postoperative complications following esophagectomy for cancer, after a mean follow-up of 4.4 years. Furthermore, patients with different levels of severity of complications had comparable HRQL. The level of HRQL in esophageal cancer patients are more likely explained by the impact of the complex procedure of the esophagectomy itself.

Contains fulltext : 287484.pdf (Publisher’s version ) (Open Access) BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P

Keenan A Ramsey,1 Suey SY Yeung,1 Anna GM Rojer,1 Noémie Gensous,2 Evans A Asamane,3 Justin Avery Aunger,3 Dmitriy Bondarev,4 Andrea Cabbia,5 Paul Doody,3 Barbara Iadarola,6,7 Belina Rodrigues,8,9 Muhammad R Tahir,10 Victor Kallen,10 Paola Pazienza,6,7 Nadine Correia Santos,8,9 Sarianna Sipilä,4 Janice L Thompson,3 Carel GM Meskers,1,11 Marijke C Trappenburg,12,13 Anna C Whittaker,15 Andrea B Maier1,14,16,17 1Department of Human Movement Sciences, @AgeAmsterdam, Amsterdam Movement Sciences, Vrije Universiteit, Faculty of Behavioural and Human Movement Sciences, Amsterdam, the Netherlands; 2Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy; 3School of Sport, Exercise & Rehabilitation Sciences, University of Birmingham, Birmingham, UK; 4Gerontology Research Center & Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland; 5Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; 6Personal Genomics s.r.l., Verona, Italy; 7Department of Biotechnology, University of Verona, Verona, Italy; 8Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; 9ICVS/3B’s, PT Government Associate Laboratory, Guimarães, Portugal; 10Department of Microbiology and System Biology, The Netherlands Organization for Applied Scientific Research, Zeist, the Netherlands; 11Department of Rehabilitation Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; 12Department of Internal Medicine, Section of Gerontology and Geriatrics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; 13Department of Internal Medicine, Amstelland Hospital, Amstelveen, the Netherlands; 14Department of Medicine and Aged Care, @Age, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria, Australia; 15Faculty of Health Sciences and Sport, University of Stirling, Scotland, UK; 16Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 17Centre for Healthy Longevity, @AgeSingapore, National University Health System, SingaporeCorrespondence: Andrea B Maier, Department of Human Movement Sciences, @AgeAmsterdam, Amsterdam Movement Sciences, Vrije Universiteit, Faculty of Behavioural and Human Movement Sciences, Van der Boechorststraat 7, Amsterdam, 1081 BT, the Netherlands, Tel +31 20 59 82000, Email a.b.maier@vu.nlPurpose: Evidence-based guidelines on nutrition and physical activity are used to increase knowledge in order to promote a healthy lifestyle. However, actual knowledge of guidelines is limited and whether it is associated with health outcomes is unclear.Participants and Methods: This inception cohort study aimed to investigate the association of knowledge of nutrition and physical activity guidelines with objective measures of physical function and physical activity in community-dwelling older adults attending a public engagement event in Amsterdam, The Netherlands. Knowledge of nutrition and physical activity according to Dutch guidelines was assessed using customized questionnaires. Gait speed and handgrip strength were proxies of physical function and the Minnesota Leisure Time Physical Activity Questionnaire was used to assess physical activity in minutes/week. Linear regression analysis, stratified by gender and adjusted for age, was used to study the association between continuous and categorical knowledge scores with outcomes.Results: In 106 older adults (mean age=70.1 SD=6.6, years) who were highly educated, well-functioning, and generally healthy, there were distinct knowledge gaps in nutrition and physical activity which did not correlate with one another (R2=0.013, p=0.245). Knowledge of nutrition or physical activity guidelines was not associated with physical function or physical activity. However, before age-adjustment nutrition knowledge was positively associated with HGS in males (B= 0.64 (95% CI: 0.05, 1.22)) and having knowledge above the median was associated with faster gait speed in females (B=0.10 (95% CI: 0.01, 0.19)).Conclusion: Our findings may represent a ceiling effect of the impact knowledge has on physical function and activity in the this high performing and educated population and that there may be other determinants of behavior leading to health status such as attitude and perception to consider in future studies.Keywords: health knowledge, attitudes, practice, lifestyle, physical performance, aged

Background: In the Netherlands, treatment with puberty suppression is available to transgender adolescents younger than age 18 years. When gender dysphoria persists testosterone or oestradiol can be added as gender-affirming hormones in young people who go on to transition. We investigated the proportion of people who continued gender-affirming hormone treatment at follow-up after having started puberty suppression and gender-affirming hormone treatment in adolescence. Methods: In this cohort study, we used data from the Amsterdam Cohort of Gender dysphoria (ACOG), which included people who visited the gender identity clinic of the Amsterdam UMC, location Vrije Universiteit Medisch Centrum, Netherlands, for gender dysphoria. People with disorders of sex development were not included in the ACOG. We included people who started medical treatment in adolescence with a gonadotropin-releasing hormone agonist (GnRHa) to suppress puberty before the age of 18 years and used GnRHa for a minimum duration of 3 months before addition of gender-affirming hormones. We linked this data to a nationwide prescription registry supplied by Statistics Netherlands (Centraal Bureau voor de Statistiek) to check for a prescription for gender-affirming hormones at follow-up. The main outcome of this study was a prescription for gender-affirming hormones at the end of data collection (Dec 31, 2018). Data were analysed using Cox regression to identify possible determinants associated with a higher risk of stopping gender-affirming hormone treatment. Findings: 720 people were included, of whom 220 (31%) were assigned male at birth and 500 (69%) were assigned female at birth. At the start of GnRHa treatment, the median age was 14·1 (IQR 13·0–16·3) years for people assigned male at birth and 16·0 (14·1–16·9) years for people assigned female at birth. Median age at end of data collection was 20·2 (17·9–24·8) years for people assigned male at birth and 19·2 (17·8–22·0) years for those assigned female at birth. 704 (98%) people who had started gender-affirming medical treatment in adolescence continued to use gender-affirming hormones at follow-up. Age at first visit, year of first visit, age and puberty stage at start of GnRHa treatment, age at start of gender-affirming hormone treatment, year of start of gender-affirming hormone treatment, and gonadectomy were not associated with discontinuing gender-affirming hormones. Interpretation: Most participants who started gender-affirming hormones in adolescence continued this treatment into adulthood. The continuation of treatment is reassuring considering the worries that people who started treatment in adolescence might discontinue gender-affirming treatment. Funding: None.

ObjectivesThe distinction between bipolar I disorder (BD-I) and bipolar II disorder (BD-II) has been a topic of long-lasting debate. This study examined differences between BD-I and BD-II in a large, global sample of OABD, focusing on general functioning, cognition and somatic burden as these domains are often affected in OABD.MethodsCross-sectional analyses were conducted with data from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) database. The sample included 963 participants aged ≥50 years (714 BD-I, 249 BD-II). Sociodemographic and clinical factors were compared between BD subtypes including adjustment for study cohort. Multivariable analyses were conducted with generalized linear mixed models (GLMMs) and estimated associations between BD subtype and (1) general functioning (GAF), (2) cognitive performance (g-score) and (3) somatic burden, with study cohort as random intercept.ResultsAfter adjustment for study cohort, BD-II patients more often had a late onset ≥50 years (p=0.008) and more current severe depression (p=0.041). BD-I patients were more likely to have a history of psychiatric hospitalization (p

Aims/hypothesis Both manifestations of kidney disease in diabetes, reduced eGFR (ml/min per 1.73 m2) and increased urinary albumin/creatinine ratio (UACR, mg/mmol), may increase the risk of specific CVD subtypes in adults with diabetes. Methods We assessed the prospective association between annually recorded measures of eGFR and UACR and the occurrence of myocardial infarction (MI), CHD, stroke, heart failure (HF) and cardiovascular mortality in 13,657 individuals with diabetes (53.6% male, age 62.3±12.1 years) from the Hoorn Diabetes Care System cohort, using data obtained between 1998 and 2018. Multivariate time-dependent Cox regression models adjusted for cardiovascular risk factors were used to estimate HRs and 95% CI. Associations of eGFR were adjusted for UACR values and vice versa. Effect modification by sex was investigated for all associations. Results After a mean follow-up period of 7 years, event rates per 1000 person-years were 3.08 for MI, 3.72 for CHD, 1.12 for HF, 0.84 for stroke and 6.25 for cardiovascular mortality. Mildly reduced eGFR (60–90 ml/min per 1.73 m2) and moderately to severely reduced eGFR (2) were associated with higher risks of MI (HR 1.52; 95% CI 1.10, 2.12 and HR 1.69; 95% CI 1.09, 2.64) and CHD (HR 1.67; 95% CI 1.23, 2.26 and HR 2.01; 95% CI 1.34, 3.02) compared with normal eGFR (>90 ml/min per 1.73 m2). Mildly reduced eGFR was associated with a higher risk of stroke (HR 2.53; 95% CI 1.27, 5.03). Moderately increased UACR (3–30 mg/mmol) and severely increased UACR (>30 mg/mmol) were prospectively associated with a higher cardiovascular mortality risk in men and women (HR 1.87; 95% CI 1.41, 2.47 and HR 2.78; 95% CI 1.78, 4.34) compared with normal UACR (30 mg/mmol, categories were combined into UACR 3.0 mg/mmol in the stratified analysis. Women but not men with UACR >3.0 mg/mmol had a significantly higher risk of HF compared with normal UACR (HR 2.79; 95% CI 1.47, 5.28). Conclusions/interpretation This study showed differential and independent prospective associations between manifestations of early kidney damage in diabetes and several CVD subtypes, suggesting that regular monitoring of both kidney function measures may help to identify individuals at higher risk of specific cardiovascular events. Graphical abstract

Purpose The aim of our study was to assess dermatological changes in transgender people after the start of gender-affirming hormonal treatment (GAHT) and to investigate whether various hormonal preparations differently affect dermatological changes in trans AFAB (assigned female at birth) people. Methods In a multicenter prospective study, 484 participants (193 assigned male at birth/AMAB and 291 AFAB) were evaluated at baseline (T0), 6 (T1) and 12 months (T2) after the start of GAHT. Hair growth was assessed by the Ferriman–Gallwey (FG) score, acne by the Global Acne Grading Scale (GAGS), and alopecia by the Norwood Hamilton (NH) score. Results In AFAB people, a significant increase in FG score and NH grade was observed across time, as well as in GAGS score in a subsample of 71 individuals (p p p = 0.021 and p = 0.003, respectively). In trans AMAB people, a significant decrease of FG score was observed across time (p Conclusion T treatment increased hair growth, acne and alopecia prevalence in AFAB people, with T undecanoate and esters influencing hair growth more than T gel. Opposite dermatological changes were observed in AMAB people.

Aims The aim of the current study was to compare cancellations or postponement of medical care among older adults during the COVID-19 pandemic between 2021 and 2020. Methods Data of respondents aged ≥ 62 years were used from the longitudinal aging study Amsterdam (LASA), collected in 2020 and 2021, directly after the main COVID-19 waves in the Netherlands. A questionnaire assessed cancellations of medical care and postponed help-seeking behavior. Descriptive analyses were performed. Results Overall, cancellations declined from 35% in 2020 (sample n = 1128) to 17% in 2021 (sample n = 1020). Healthcare-initiated cancellations declined from 29 to 8%. Respondent-initiated cancellations declined from 12 to 7%. Postponed help-seeking remained around 8%. Conclusions In 2021, less cancellations were reported compared to just after the first wave of the pandemic in 2020, while postponed help-seeking remained the same. It is important to investigate how cancellations and postponed help-seeking can be prevented in future pandemics.

Understanding and communicating the risk of pregnancy complications post-living kidney donation is imperative as the majority of living kidney donors (LKD) are women of childbearing age. We aimed to identify all original research articles examining complications in post-donation pregnancies and compared the quality and consistency of related guidelines. We searched Embase, MEDLINE, PubMed, society webpages, and guideline registries for English-language publications published up until December 18, 2020. Ninety-three articles were screened from which 16 studies were identified, with a total of 1399 post-donation pregnancies. The outcome of interest, post-donation pregnancy complications, was not calculable, and only a narrative synthesis of the evidence was possible. The absolute risk of pre-eclampsia increased from similar to 1%-3% pre-donation (lower than the general population) to similar to 4%-10% post-donation (comparable to the general population). The risks of adverse fetal and neonatal outcomes were no different between post-donation and pre-donation pregnancies. Guidelines and consensus statements were consistent in stating the need to inform LKDs of their post-donation pregnancy risk, however, the depth and scope of this guidance were variable. While the absolute risk of pregnancy complications remains low post-donation, a concerted effort is required to better identify and individualize risk in these women, such that consent to donation is truly informed.

Health informatics (also referred to as medical informatics or biomedical informatics) is an interdisciplinary field that deals with health-related data in healthcare and with the technologies that are used to support healthcare services. While the goal of some health informatics systems is to automate processes, the more common goal is to help clinicians, patients, policymakers, and others to manage health information, and to communicate that information efficiently and effectively to end users. Thus, there is considerable overlap between the fields of health informatics and health communication, and this intriguing intersection between the two fields opens many opportunities for innovation. Health communication is often visible in health informatics in the area of patient communication. Examples of this include patient self-management tools that support behavior change. Correspondingly, health informatics is often visible in health communication in the use of computational methods and “big data” to build on communication theory. Future research in health communication will likely involve more and more intensive use of information technology. This can bring exciting new possibilities for both interventions and analytical techniques, yet researchers should ensure that information technology interventions respect participants' privacy and guarantee their safety. Investigating the effect of information technology on communications between healthcare professionals and with patients also offers interesting opportunities for collaborative research.

Purpose Our objective is to evaluate the effect of habituation on the altered ear canal acoustics after canal wall down mastoidectomy. Methods A total of 11 participants with single sided dry cavities and normal contralateral ear canals with normal hearing thresholds were included in the study. Filtered sound fragments were created that simulate the different acoustic properties based on the participants Real Ear to Coupler Difference (RECD) of the cavity ear and the contralateral normal ear canal. These filtered sound fragments are presented to the cavity ear canal and the contralateral normal ear canal using inserts earphones. Participants performed a subjective quality assessment of the sound fragments using paired comparison with a seven-point scale (− 3 till + 3). Results Mean assessment of sound quality revealed the following results; naturalness of sounds of the cavity ear canal is 0.29 (± 1.41; ns) in favour of the filtered sound fragment of the normal ear canal. Mean assessment of sharpness of sounds in the cavity ear canal is 1.55 (± 1.21, p = 0.55) in favour of the filtered sound fragment of the normal ear canal. Overall preference in the cavity ear canal was in favour of the normal ear canal acoustics 0.72 (SD ± 1.54 p = 0.224). Conclusions Patients with cavity ear canals seem to habituate to their altered ear canal acoustics. Transforming the ear canal acoustics of the cavity ear to normal ear canal acoustics seem to sharpen the incoming sounds. Overall assessment of quality of sound of the normal ear canal acoustics is better than the cavity acoustics.

Background: The currently available mortality prediction models (MPM) have suboptimal performance when predicting early mortality (30-days) following transcatheter aortic valve implantation (TAVI) on various external populations. We developed and validated a new TAVI-MPM based on a large number of predictors with recent data from a national heart registry. Methods: We included all TAVI-patients treated in the Netherlands between 2013 and 2018, from the Netherlands Heart Registration. We used logistic-regression analysis based on the Akaike Information Criterion for variable selection. We multiply imputed missing values, but excluded variables with >30% missing values. For internal validation, we used ten-fold cross-validation. For temporal (prospective) validation, we used the 2018-data set for testing. We assessed discrimination by the c-statistic, predicted probability accuracy by the Brier score, and calibration by calibration graphs, and calibration-intercept and calibration slope. We compared our new model to the updated ACC-TAVI and IRRMA MPMs on our population. Results: We included 9144 TAVI-patients. The observed early mortality was 4.0%. The final MPM had 10 variables, including: critical-preoperative state, procedure-acuteness, body surface area, serum creatinine, and diabetes-mellitus status. The median c-statistic was 0.69 (interquartile range [IQR] 0.646–0.75). The median Brier score was 0.038 (IQR 0.038–0.040). No signs of miscalibration were observed. The c-statistic's temporal-validation was 0.71 (95% confidence intervals 0.64–0.78). Our model outperformed the updated currently available MPMs ACC-TAVI and IRRMA (p value < 0.05). Conclusion: The new TAVI-model used additional variables and showed fair discrimination and good calibration. It outperformed the updated currently available TAVI-models on our population. The model's good calibration benefits preprocedural risk-assessment and patient counseling.

Background The number of studies applying machine learning (ML) to predict acute kidney injury (AKI) has grown steadily over the past decade. We assess and critically appraise the state of the art in ML models for AKI prediction, considering performance, methodological soundness, and applicability. Methods We searched PubMed and ArXiv, extracted data, and critically appraised studies based on the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD), Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS), and Prediction Model Risk of Bias Assessment Tool (PROBAST) guidelines. Results Forty-six studies from 3166 titles were included. Thirty-eight studies developed a model, five developed and externally validated one, and three studies externally validated one. Flexible ML methods were used more often than deep learning, although the latter was common with temporal variables and text as predictors. Predictive performance showed an area under receiver operating curves ranging from 0.49 to 0.99. Our critical appraisal identified a high risk of bias in 39 studies. Some studies lacked internal validation, whereas external validation and interpretability of results were rarely considered. Fifteen studies focused on AKI prediction in the intensive care setting, and the US-derived Medical Information Mart for Intensive Care (MIMIC) data set was commonly used. Reproducibility was limited as data and code were usually unavailable. Conclusions Flexible ML methods are popular for the prediction of AKI, although more complex models based on deep learning are emerging. Our critical appraisal identified a high risk of bias in most models: Studies should use calibration measures and external validation more often, improve model interpretability, and share data and code to improve reproducibility.

Contains fulltext : 252036.pdf (Publisher’s version ) (Closed access) BACKGROUND: Most physicians encounter pregnant women with cancer incidentally, leading to a lack of expertise or confidence to inform and treat these patients based on the most recent guidelines and expert opinions. In the Netherlands, a national multidisciplinary tumour board for cancer, infertility and pregnancy (CIP-MDT) was founded in December 2012, including 35 specialists from a variety of disciplines. This study evaluates the frequency of consultation of the CIP-MDT, the types of questions asked and the satisfaction of consulting physicians with its existence. METHODOLOGY: Of all requests to the CIP-MDT between December 2012 and June 2021, tumour type, stage, gestational age at diagnosis and recommendations were collected and analysed. For evaluating the methods of the CIP-MDT, a survey with questions regarding experiences with the CIP-MDT and its impact on treatment decisions was sent out to physicians that consulted the CIP-MDT. RESULTS: Recommendations (n = 213) concerned preferred and safest options for imaging, treatment options during pregnancy, possible effects on the child and fertility preserving options. Most frequently discussed malignancies were breast cancer (n = 66), cervical cancer (n = 34), haematological malignancies (n = 32) and melanoma (n = 21). The questionnaire was completed by 54% of the physicians (n = 50). Satisfaction with the recommendations of the CIP-MDT was high, and 94% of the physicians informed their patients about consulting the CIP-MDT and felt supported by the received recommendations. DISCUSSION: The national Dutch CIP-MDT contributes to a high level of satisfaction among physicians requesting advice. Further research should be executed to confirm that a CIP-MDT improves the outcomes for pregnant women and their children.

BACKGROUND AND PURPOSE: Supervised deep learning is the state-of-the-art method for stroke lesion segmentation on NCCT. Supervised methods require manual lesion annotations for model development, while unsupervised deep learning methods such as generative adversarial networks do not. The aim of this study was to develop and evaluate a generative adversarial network to segment infarct and hemorrhagic stroke lesions on follow-up NCCT scans.MATERIALS AND METHODS: Training data consisted of 820 patients with baseline and follow-up NCCT from 3 Dutch acute ischemic stroke trials. A generative adversarial network was optimized to transform a follow-up scan with a lesion to a generated baseline scan without a lesion by generating a difference map that was subtracted from the follow-up scan. The generated difference map was used to automatically extract lesion segmentations. Segmentation of primary hemorrhagic lesions, hemorrhagic transformation of ischemic stroke, and 24-hour and 1-week follow-up infarct lesions were evaluated relative to expert annotations with the Dice similarity coefficient, Bland-Altman analysis, and intraclass correlation coefficient.RESULTS: The median Dice similarity coefficient was 0.31 (interquartile range, 0.08-0.59) and 0.59 (interquartile range, 0.29-0.74) for the 24-hour and 1-week infarct lesions, respectively. A much lower Dice similarity coefficient was measured for hemorrhagic transformation (median, 0.02; interquartile range, 0-0.14) and primary hemorrhage lesions (median, 0.08; interquartile range, 0.01-0.35). Predicted lesion volume and the intraclass correlation coefficient were good for the 24-hour (bias, 3 mL; limits of agreement, -64-59 mL; intraclass correlation coefficient, 0.83; 95% CI, 0.78-0.88) and excellent for the 1-week (bias, -4 m; limits of agreement,-66-58 mL; intraclass correlation coefficient, 0.90; 95% CI, 0.83-0.93) follow-up infarct lesions.CONCLUSIONS: An unsupervised generative adversarial network can be used to obtain automated infarct lesion segmentations with a moderate Dice similarity coefficient and good volumetric correspondence.

Introduction: Treatment options for Waldenström's Macroglobulinemia (WM) have expanded rapidly in the last decades. However, there is no consensus on a preferred treatment. Therefore, patient preferences become increasingly important in making individualized treatment plans. Still, WM patients' priorities and perspectives regarding their treatment options are unknown. We evaluated treatment preferences of WM patients using a discrete choice experiment (DCE). Methods: A mixed-method approach was utilized for identification and selection of attributes/levels. The DCE questionnaire included five attributes: type of agent (targeted versus chemotherapy); frequency and route of administration; 5-year progression-free survival (PFS); adverse events; and risk of secondary malignancies. An orthogonal design and a mixed logit panel data model were used to construct choice tasks and assess patient preferences, respectively. Results: Three hundred thirty WM patients participated in the project. In total, 214 (65%) complete questionnaires were included for data analysis. The 5-year PFS, followed by risk of secondary malignancies were the most important attributes for making treatment choices. Regarding side effects, patients chose to avoid neuropathy the most compared to nausea/vomiting and extreme fatigue. Patients preferred a fixed-duration treatment with IV/SC administration at the hospital over a continuous daily oral regimen at home. Conclusion: These are the first systematic data obtained on WM patient preferences for treatment. The results may help discussions with individual patients about their treatment choices. Also, these data can help design clinical trials in WM and inform health-care decision-making regarding outcomes that are most relevant to patients.

BACKGROUND: Health-related Quality of life (HRQoL) in patients with Barrett's esophagus (BE), a premalignant condition, may be influenced by gastroesophageal reflux disease (GERD) symptoms and the risk of developing esophageal adenocarcinoma.METHODS: We aim to investigate HRQoL in non-dysplastic Barrett Esophagus (NDBE) patients, identify factors associated with a negative illness perception of the diagnosis BE and compare outcomes between patients treated in a specialized BE center with non-expert centers. In this multi-center cross-sectional study, HRQoL of NDBE patients were assessed using the Short Form 36, Hospital Anxiety and Depression Scale, Cancer worry Scale, and Reflux Disease Questionnaire. A multivariable, linear regression analysis was conducted to assess factors associated with illness perception (Illness perception scale) of the BE diagnosis. Outcome parameters of patients from expert centers were compared to non-expert centers.RESULTS: A total of 859 NDBE patients (mean age 63.6% and 74.5% male), of which 640 from BE expert centers were included. BE patients scored similar or higher means (i.e. better) on generic HRQoL in comparison with a Dutch norm population. The multivariable regression model showed that cancer worry, GERD symptoms, signs of anxiety and depression, and female gender were associated with a negative illness perception of BE. GERD symptoms were reported in the minority (22.4%) of BE patients. Levels of anxiety symptoms were comparable to a Dutch norm population (mean 3.7 vs. 3.9 p 0.183) and lower for depression symptoms (mean 6.8 vs. 7.6 p < 0.001). Overall, there were no differences found on outcomes between expert centers and non-expert centers.CONCLUSION: NDBE patients scored similar or better on generic HRQoL, anxiety and depression than an age and gender matched norm population. The presence of cancer worry, gastrointestinal symptoms, anxiety and depression, and female gender are factors associated with a negative illness perception of the diagnosis BE.

Background: This study aimed to examine the associations of plasma superoxide dismutase (SOD) activity, an indicator of oxidative stress, with disability in activities of daily living (ADL) and objective physical functioning among Chinese older adults. Methods: We used cross-sectional data of 2223 older adults (≥65 years, including 1505 adults≥80 years) from the 2011/2012 main survey of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) and the 2012 biomarker sub-study. Plasma SOD activity was assessed by the T-SOD assay kit based on the hydroxylamine method. Outcomes included ADL disability and disability in three objective physical tasks (standing up from a chair, picking up a book from the floor, and turning around 360°). Logistic regression models were used to examine the associations of plasma SOD activity with outcomes. Results: After controlling for age and sex, compared with participants in the lowest quartile group of SOD activity, those in the highest quartile group had 31% lower odds of ADL disability (odds ratio [OR]: 0.69; 95%CI: 0.48, 0.98); 60% lower odds of disability in standing up from a chair (OR: 0.40; 95%CI: 0.25, 0.63); and 57% lower odds of disability in picking up a book from a floor (OR: 0.43; 95%CI: 0.28, 0.65). The results did not change substantially after controlling for additional covariates. We did not observe statistically significant age and sex differences. Conclusions: Overall, plasma SOD activity was associated with subjectively and objectively measured disability in Chinese older adults, highlighting the potential of SOD activity to serve as a biomarker of physical functioning.

Purpose: Intensive care is a stressful environment in which team-family conflicts commonly occur. If managed poorly, conflicts can have negative effects on all parties involved. Previous studies mainly investigated these conflicts and their management in a retrospective way. This study aimed to prospectively explore team-family conflicts, including its main topics, complicating factors, doctors’ conflict management strategies and the effect of these strategies. Methods: Conversations between doctors in the neonatal, pediatric, and adult intensive care unit of a large university-based hospital and families of critically ill patients were audio-recorded from the moment doubts arose whether treatment was still in patients’ best interest. Transcripts were coded and analyzed using a qualitative deductive approach. Results: Team-family conflicts occurred in 29 out of 101 conversations (29%) concerning 20 out of 36 patients (56%). Conflicts mostly concerned more than one topic. We identified four complicating context- and/or family-related factors: diagnostic and prognostic uncertainty, families’ strong negative emotions, limited health literacy, and burden of responsibility. Doctors used four overarching strategies to manage conflicts, namely content-oriented, process-oriented, moral and empathic strategies. Doctors mostly used content-oriented strategies, independent of the intensive care setting. They were able to effectively address conflicts in most conversations. Yet, if they did not acknowledge families’ cues indicating the existence of one or more complicating factors, conflicts were likely to linger on during the conversation. Conclusion: This study underlines the importance of doctors tailoring their communication strategies to the concrete conflict topic(s) and to the context- and family-related factors which complicate a specific conflict.

Purpose Few data are available regarding subjective complaints and quality of life (QoL) after subtotal petrosectomy (STP). The purpose of our study was to assess long-term surgical results after STP, and to evaluate disease-specific, patient-reported outcomes including QoL and subjective hearing. Methods A retrospective cohort study, including a postal survey, was performed in the Amsterdam University Medical Centers (Amsterdam UMC) location Academic Medical Centre (AMC). All patients who underwent a STP between 1990 and 2018 were included. Patient characteristics, indication for surgery, adverse events, disease recidivism, and patient-reported health outcomes were evaluated. Results 181 patients (183 ears) underwent a STP for several indications. The main indication was chronic otitis media (COM) with or without cholesteatoma (69%). In the total cohort, 8 residual cholesteatoma (5%) and 6 inclusion cholesteatoma 4% were detected. Postoperative (functional) health outcomes showed a significant negative impact on QoL in the STP cohort compared to normative data. Compared to patients without ear problems, the postoperative STP patients scored worse on almost all domains of the Chronic Ear Survey (CES) (p Z-scores in almost all subscales, indicating lower levels of QoL compared to Dutch reference values. Most subscales of the Amsterdam Inventory for Auditory Disability and Handicap (AIADH) demonstrate a large-effect size in disadvantage of the STP cohort when compared to Dutch reference values. Conclusion STP is a suitable technique to tackle severe ear disease. Despite its favourable surgical results, STP has a negative impact on several domains of patient’s QoL.

Background The feasibility of implementing an advance care planning (ACP) program in daily clinical practice for glioblastoma patients is unknown. We aimed to evaluate a previously developed disease-specific ACP program, including the optimal timing of initiation and the impact of the program on several patient-, proxy-, and care-related outcomes. Methods The content and design of the ACP program were evaluated, and outcomes including health-related quality of life (HRQoL), anxiety and depression, and satisfaction with care were measured every 3 months over 15 months. Results Eighteen patient-proxy dyads and two proxies participated in the program. The content and design of the ACP program were rated as sufficient. The preference for the optimal timing of initiation of the ACP program varied widely, however, most of the participants preferred initiation shortly after chemoradiation. Over time, aspects of HRQoL remained stable in our patient population. Similarly, the ACP program did not decrease the levels of anxiety and depression in patients, and a large proportion of proxies reported anxiety and/or depression. The needed level of support for proxies was relatively low throughout the disease course, and the level of feelings of caregiver mastery was relatively high. Overall, patients were satisfied with the provided care over time, whereas proxies were less satisfied in some aspects. Conclusions The content and design of the developed disease-specific ACP program were rated as satisfactory. Whether the program has an actual impact on patient-, proxy-, and care-related outcomes proxies remain to be investigated.

Contains fulltext : 287686.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To determine the prevalence of depression, anxiety, and posttraumatic stress disorder (PTSD) years after hyperemesis gravidarum (HG) and its association with HG severity. MATERIAL AND METHODS: This prospective cohort study consisted of a follow-up of 215 women admitted for HG, who were eligible to participate in a randomized controlled trial and either declined or agreed to be randomized between 2013 and 2016 in 19 hospitals in the Netherlands. Participants completed the Hospital Anxiety and Depression Scale (HADS) six weeks postpartum and during follow-up and the PTSD checklist for DSM-5 (PCL-5) during follow-up. An anxiety or depression score ≥8 is indicative of an anxiety or depression disorder and a PCL-5 ≥ 31 indicative of PTSD. Measures of HG severity were symptom severity (PUQE-24: Pregnancy Unique Quantification of Emesis), weight change, duration of admissions, readmissions, and admissions after the first trimester. RESULTS: About 54/215 participants completed the HADS six weeks postpartum and 73/215 participants completed the follow-up questionnaire, on average 4.5 years later. Six weeks postpartum, 13 participants (24.1%) had an anxiety score ≥8 and 11 participants (20.4%) a depression score ≥8. During follow-up, 29 participants (39.7%) had an anxiety score ≥8, 20 participants (27.4%) a depression score ≥8, and 16 participants (21.9%) a PCL-5 ≥ 31.Multivariable logistic regression analysis showed that for every additional point of the mean PUQE-24 three weeks after inclusion, the likelihood of having an anxiety score ≥8 and PCL-5 ≥ 31 at follow-up increased with OR 1.41 (95% CI: 1.10;1.79) and OR 1.49 (95% CI: 1.06;2.10) respectively. CONCLUSION: Depression, anxiety, and PTSD symptoms are common years after HG occurred.

Objective ‘Better By Moving’ is a multifaceted intervention developed and implemented in collaboration with patients and healthcare professionals to improve physical activity in hospitalized adults. This study aimed to understand if, how and why ‘Better By Moving’ resulted in higher levels of physical activity by evaluating both outcomes and implementation process. Design Mixed-methods study informed by the Medical Research Council guidance. Setting Tertiary hospital. Participants Adult patients admitted to surgery, haematology, infectious diseases and cardiology wards, and healthcare professionals. Measures Physical activity was evaluated before and after implementation using the Physical Activity Monitor AM400 on one random day during hospital stay between 8 am and 8 pm. Furthermore, the time spent lying on bed, length of stay and discharge destination was investigated. The implementation process was evaluated using an audit trail, surveys and interviews. Results There was no significant difference observed in physical activity (median [IQR] 23 [12–51] vs 27 [17–55] minutes, P = 0.107) and secondary outcomes before-after implementation. The intervention components’ reach was moderate and adoption was low among patients and healthcare professionals. Patients indicated they perceived more encouragement from the environment and performed exercises more frequently, and healthcare professionals signalled increased awareness and confidence among colleagues. Support (priority, resources and involvement) was perceived a key contextual factor influencing the implementation and outcomes. Conclusion Although implementing ‘Better By Moving’ did not result in significant improvements in outcomes at our centre, the process evaluation yielded important insights that may improve the effectiveness of implementing multifaceted interventions aiming to improve physical activity during hospital stay.

Purpose The Dutch Hip Fracture Audit (DHFA), a nationwide hip fracture registry in the Netherlands, registers hip fracture patients and aims to improve quality of care since 2016. This study shows trends in the data quality during the first 5 years of data acquisition within the DHFA, as well as trends over time for designated quality indicators (QI). Methods All patients registered in the DHFA between 1-1-2016 and 31-12-2020 were included. Data quality-registry case coverage and data completeness-and baseline characteristics are reported. Five QI are analysed: Time to surgery Results In 2020, the case capture of the DHFA comprised 85% of the Dutch hip fracture patients, 66/68 hospitals participated. The average of missing clinical values was 7.5% in 2016 and 3.2% in 2020. The 3 months follow-up completeness was 36.2% (2016) and 46.8% (2020). The QI ‘time to surgery’ was consistently high, assessment for osteoporosis remained low, orthogeriatric co-management scores increased without significance, registration of functional outcomes improved significantly and 30-day mortality rates remained unchanged. Conclusion The DHFA has successfully been implemented in the past five years. Trends show improvement on data quality. Analysis of several QI indicate points of attention. Future perspectives include lowering the burden of registration, whilst improving (registration of) hip fracture patients outcomes.

Contains fulltext : 251275.pdf (Publisher’s version ) (Open Access) Objective: To evaluate a pilot implementation of an organizational-level intervention. The Participatory Approach (PA) was used to create a supportive work environment for employees with chronic conditions, with a key role for occupational physicians (OPs). Methods: 28 semi-structured interviews were conducted with OPs and stakeholders within their organizations. Furthermore, observational data and research notes were gathered. Data analysis occurred through content analysis. Results: Recruitment of organizations was challenging, with a reach of 25%. Dose delivered, dose received and fidelity differed across the three organizations. Organizations were positive about the PA as a method to improve support for employees with chronic conditions. Conclusions: The PA could be of added value for creating a supportive work environment. However, research is needed on activating organizations to improve support for employees with chronic conditions. 10 p.

INTRODUCTION: Orthostatic hypotension is a common condition associated with an increased mortality risk. This study investigates this association specifically in geriatric outpatients and additionally focuses on the duration and magnitude of orthostatic hypotension. METHODS: In this observational prospective cohort study with geriatric outpatients from the Amsterdam Ageing cohort, we differentiated orthostatic hypotension in early orthostatic hypotension (EOH) and delayed/prolonged orthostatic hypotension (DPOH). The magnitude of drop in both SBP and DBP after either 1 or 3 min was quantified. Mortality data was obtained from the Dutch municipal register. Cox proportional hazard models were used to determine the association between orthostatic hypotension and mortality, adjusted for sex and age (model 1), additionally adjusted for orthostatic hypotension-inducing drugs + SBP (model 2) and the presence of cardiovascular disease and diabetes (model 3). Stratified analyses in patients with geriatric deficits were performed. RESULTS: We included 1240 patients (mean age 79.4 ± 6.9 years, 52.6% women). Prevalence of orthostatic hypotension was 443 (34.9%); 148 (11.9%) patients had EOH and 285 (23%) DPOH. DPOH was associated with a higher mortality risk [hazard ratio, 95% CI 1.69 (1.28-2.22)] whereas EOH was not associated with mortality risk. This association did not differ in patients with geriatric deficits. Furthermore, the magnitude of drop in both SBP and DBP was associated with a higher mortality risk. CONCLUSION: The presence of DPOH and the magnitude of both systolic and diastolic orthostatic hypotension are related to an increased mortality risk in geriatric outpatients. Whether the duration of orthostatic hypotension and magnitude of the drop in blood pressure is causally related to mortality risk or whether it is a sign of decreased resilience remains to be elucidated.

Background: Over the past decade, antiretroviral therapy (ART) regimens that include integrase strand inhibitors (INSTIs) have become the most commonly used for people with HIV starting ART. Although trials and observational studies have compared virological failure on INSTI-based with other regimens, few data are available on mortality in people with HIV treated with INSTIs in routine care. Therefore, we compared all-cause mortality between different INSTI-based and non-INSTI-based regimens in adults with HIV starting ART from 2013 to 2018. Methods: This cohort study used data on people with HIV in Europe and North America from the Antiretroviral Therapy Cohort Collaboration (ART-CC) and UK Collaborative HIV Cohort (UK CHIC). We studied the most common third antiretroviral drugs (additional to nucleoside reverse transcriptase inhibitor) used from 2013 to 2018: rilpivirine, darunavir, raltegravir, elvitegravir, dolutegravir, efavirenz, and others. Adjusted hazard ratios (aHRs; adjusted for clinical and demographic characteristics, comorbid conditions, and other drugs in the regimen) for mortality were estimated using Cox models stratified by ART start year and cohort, with multiple imputation of missing data. Findings: 62 500 ART-naive people with HIV starting ART (12 422 [19·9%] women; median age 38 [IQR 30-48]) were included in the study. 1243 (2·0%) died during 188 952 person-years of follow-up (median 3·0 years [IQR 1·6-4·4]). There was little evidence that mortality rates differed between regimens with dolutegravir, elvitegravir, rilpivirine, darunavir, or efavirenz as the third drug. However, mortality was higher for raltegravir compared with dolutegravir (aHR 1·49, 95% CI 1·15-1·94), elvitegravir (1·86, 1·43-2·42), rilpivirine (1·99, 1·49-2·66), darunavir (1·62, 1·33-1·98), and efavirenz (2·12, 1·60-2·81) regimens. Results were similar for analyses making different assumptions about missing data and consistent across the time periods 2013-15 and 2016-18. Rates of virological suppression were higher for dolutegravir than other third drugs. Interpretation: This large study of patients starting ART since the introduction of INSTIs found little evidence that mortality rates differed between most first-line ART regimens; however, raltegravir-based regimens were associated with higher mortality. Although unmeasured confounding cannot be excluded as an explanation for our findings, virological benefits of first-line INSTIs-based ART might not translate to differences in mortality. We would like to thank our funders (US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council) and all patients and the clinical teams associated with the participating cohort studies. The antiretroviral therapy cohort collaboration is funded by the US National Institute on Alcohol Abuse and Alcoholism (U01-AA026209). UK Collaborative HIV Cohort is funded by the UK Medical Research Council (grant numbers G0000199, G0600337, G0900274, and M004236/1). JACS is funded by National Institute for Health Research Senior Investigator award (NF-SI-0611-10168). AT is funded by the Wellcome Trust under a Sir Henry Wellcome Postdoctoral Fellowship (222770/Z/21/Z). Funding for the individual antiretroviral therapy cohort collaboration cohorts included in this analysis was from Alberta Health, Gilead, National Agency for AIDS Research (France REcherche Nord&Sud Sida-hiv Hépatites), the French Ministry of Health, the Austrian Agency for Health and Food Safety, Stichting HIV Monitoring, the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment, the TP-HIV by the German Centre for Infection Research (NCT02149004), Instituto de Salud Carlos III (through the Red Temática de Investigación Cooperativa en Sida [RD06/006, RD12/0017/0018, and RD16/0002/0006]) as part of the Plan Nacional I + D + i. Other funders of the individual cohorts participating data for this analysis are ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional, ViiV Healthcare, Preben og Anna Simonsens Fond, ANRS-Maladies infectieuses émergentes, Institut National de la Santé et de la Recherche Médicale (INSERM), Bristol Myers Squibb, Janssen, Merck, the US National Institute on Alcohol Abuse and Alcoholism (U01-AA026230), the Spanish Ministry of Health, the Swiss National Science Foundation (grant 33CS30_134277), Centers for AIDS Research Network of Integrated Clinical Systems (1R24 AI067039-1, P30-AI-027757), the US Department of Veterans Affairs, the US National Institute on Alcohol Abuse and Alcoholism (U01-AA026224, U01-AA026209, U24-AA020794), the Veterans Health Administration Office of Research and Development, and the US National Institute of Allergy and Infectious Diseases (Tennessee Center for AIDS Research P30 AI110527). Sí

Homozygous familial hypercholesterolaemia (HoFH) is a life-threatening disorder characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C) levels. Untreated, severe atherosclerotic cardiovascular disease (ASCVD), including aortic valve stenosis (AVS), may already occur in childhood. Another important genetic risk factor for ASCVD and AVS is elevated lipoprotein(a) [Lp(a)], which is highly prevalent in the general paediatric population. However, data on Lp(a) in children with HoFH are scarce. Therefore, we performed a cross-sectional study to evaluate Lp(a) levels in children with HoFH and compared them to children with heterozygous FH (HeFH) and unaffected children. Adjusted least-square mean (95% CI) Lp(a) levels in HoFH (n=29), HeFH (n=101) and unaffected children (n=102) were 18.7 (12.0-29.1), 15.3 (11.8-19.8) and 10.5 (8.3-13.2) mg/dL, respectively (p-for-trend=0.007). Lp(a) levels in children with HoFH were higher than in children with HeFH and in unaffected children. Given the very high ASCVD risk with HoFH, identifying other risk factors such as elevated Lp(a) in these children is important. Therefore, Lp(a) levels should be measured at least once in all children with HoFH.

Background Falls in older people are common and morbid. Prediction models can help identifying individuals at higher fall risk. Electronic health records (EHR) offer an opportunity to develop automated prediction tools that may help to identify fall-prone individuals and lower clinical workload. However, existing models primarily utilise structured EHR data and neglect information in unstructured data. Using machine learning and natural language processing (NLP), we aimed to examine the predictive performance provided by unstructured clinical notes, and their incremental performance over structured data to predict falls. Methods We used primary care EHR data of people aged 65 or over. We developed three logistic regression models using the least absolute shrinkage and selection operator: one using structured clinical variables (Baseline), one with topics extracted from unstructured clinical notes (Topic-based) and one by adding clinical variables to the extracted topics (Combi). Model performance was assessed in terms of discrimination using the area under the receiver operating characteristic curve (AUC), and calibration by calibration plots. We used 10-fold cross-validation to validate the approach. Results Data of 35,357 individuals were analysed, of which 4,734 experienced falls. Our NLP topic modelling technique discovered 151 topics from the unstructured clinical notes. AUCs and 95% confidence intervals of the Baseline, Topic-based and Combi models were 0.709 (0.700–0.719), 0.685 (0.676–0.694) and 0.718 (0.708–0.727), respectively. All the models showed good calibration. Conclusions Unstructured clinical notes are an additional viable data source to develop and improve prediction models for falls compared to traditional prediction models, but the clinical relevance remains limited.

Background: Bivalent mRNA-based COVID-19 vaccines encoding the ancestral and omicron spike (S) protein were developed as a countermeasure against antigenically distinct SARS-CoV-2 variants. We aimed to assess the (variant-specific) immunogenicity and reactogenicity of mRNA-based bivalent omicron (BA.1) vaccines in individuals who were primed with adenovirus-based or mRNA-based vaccines encoding the ancestral spike protein. Methods: We analysed results of the direct boost group of the SWITCH ON study, an open-label, multicentre, randomised controlled trial. Health-care workers from four academic hospitals in the Netherlands aged 18–65 years who had completed a primary COVID-19 vaccination regimen and received one booster of an mRNA-based vaccine, given no later than 3 months previously, were eligible. Participants were randomly assigned (1:1) using computer software in block sizes of 16 and 24 to receive an omicron BA.1 bivalent booster straight away (direct boost group) or a bivalent omicron BA.5 booster, postponed for 90 days (postponed boost group), stratified by priming regimen. The BNT162b2 OMI BA.1 boost was given to participants younger than 45 years, and the mRNA-1273.214 boost was given to participants 45 years or older, as per Dutch guidelines. The direct boost group, whose results are presented here, were divided into four subgroups for analysis: (1) Ad26.COV2.S (Johnson & Johnson) prime and BNT162b2 OMI BA.1 (BioNTech–Pfizer) boost (Ad/P), (2) mRNA-based prime and BNT162b2 OMI BA.1 boost (mRNA/P), (3) Ad26.COV2.S prime and mRNA-1273.214 (Moderna) boost (Ad/M), and (4) mRNA-based prime and mRNA-1273.214 boost (mRNA/M). The primary outcome was fold change in S protein S1 subunit-specific IgG antibodies before and 28 days after booster vaccination. The primary outcome and safety were assessed in all participants except those who withdrew, had a SARS-CoV-2 breakthrough infection, or had a missing blood sample at day 0 or day 28. This trial is registered with ClinicalTrials.gov, NCT05471440. Findings: Between Sept 2 and Oct 4, 2022, 219 (50%) of 434 eligible participants were randomly assigned to the direct boost group; 187 participants were included in the primary analyses; exclusions were mainly due to SARS-CoV-2 infection between days 0 and 28. From the 187 included participants, 138 (74%) were female and 49 (26%) were male. 42 (22%) of 187 participants received Ad/P and 44 (24%) mRNA/P (those aged

Observational studies have shown consistently that modifiable risk factors during life are associated with increased dementia risk in old age but randomized controlled trials (RCTs) on dementia prevention evaluating the treatment of these risk factors did not find consistent effects on cognitive outcomes. The discrepancy in findings is potentially attributable to inherent differences between the two study designs. Although RCTs are the gold standard for establishing causality, designing and conducting an RCT for dementia prevention is complex. Quasi-experimental studies (QESs) may contribute to investigating causality without randomization. QESs use variation in exposure to a risk factor or intervention in an observational setting to deduct causal effects. Design-specific approaches are used to control for confounding, the main caveat of QESs. In this article we address the challenges, opportunities, and limitations of QESs for research into dementia prevention. Highlights: Despite consistent associations between modifiable risk factors and dementia, the mostly neutral effects of randomized controlled trials (RCTs) challenge the causality of these associations. RCTs in the field of dementia prevention are often problematic due to ethical, practical, or financial constraints, and their results may have limited generalizability. Four quasi-experimental study (QES) designs may be suitable to study causality between risk factors and dementia; we critically appraise these study designs for dementia-prevention studies. We describe how specific QES designs can be used to study the effects of risk-factor modification for 12 known risk factors for dementia.

Purpose Worldwide, an increasing number of people are diagnosed with atypical Parkinsonism or idiopathic Parkinson’s disease (PD). Periods of acute functional decline, triggered by acute disease, are common. Rehabilitation is often necessary to restore functioning. Skilled nursing facilities (SNFs) in the Netherlands have developed evidence-based geriatric rehabilitation for Parkinson (GR-P) programs. However, data on the experiences and needs of patients and their caregivers are lacking. This study aims to address these, in order to propose recommendations for improvement. Methods We performed a qualitative study, using semi-structured interviews in two Dutch SNFs offering GR-P. Nine patients with PD and six informal caregivers were included. We subjected verbatim transcripts of 15 interviews to qualitative analysis. Results Data saturation was reached after 15 interviews. Three overarching themes emerged: (1) autonomy, (2) sharing information and (3) contact with others. Loss of autonomy was linked to the underlying disease and the rehabilitation environment itself. Patients and caregivers felt overwhelmed by events before and during rehabilitation, expressing a need to receive information and discuss prior experiences. They considered communication between hospitals and SNFs to be poor. Patients did not always appreciate contact with peers. Both patients and caregivers appreciated empathic healthcare personnel with a firm knowledge on PD. Conclusions Autonomy, sharing information and contact with others are central themes for patients and caregivers during GR-P in SNFs. We recommend actively exploring these three central themes with every patient and caregiver entering a GR-P program and offering staff continuing education on PD, in order to improve care.

Involving patients in health research requires a new way of working for all stakeholders involved, including researchers. This research aimed (1) to gain deeper insight into the experiences and needs of researchers regarding meaningful patient involvement and (2) to incorporate these insights into an online tool. This was done in a transdisciplinary research process, including three focus group discussions and three test sessions. We used the Social Cognitive Theory in the analysis process to reflect on how the tool addresses the complex personal, behavioural, and environmental factors that shape researchers’ experiences and needs. Identified factors were categorized into three themes: added value, perceived difficulty and patient-researcher role patterns. A tool was developed that addresses these factors, aiming to stimulate meaningful involvement by encouraging (self)reflection, experimentation, and learning-by-doing. It provides one element in a bigger systems approach to further stimulate patient involvement.