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The objective of the study was to gain an insight into the perceptions and experiences of patients with rheumatoid arthritis and a high cardiovascular disease risk (CVD-RA) when undergoing an exercise intervention aimed at improving their cardiorespiratory fitness. This qualitative study was part of a pilot study, which investigated the effects of an exercise intervention on cardiorespiratory fitness in patients with CVD-RA. Six patients were invited to participate in face-to-face semi-structured interviews. We invited patients who completed the exercise intervention as well as patients who withdrew from the exercise intervention. The interviews were analyzed according to the method of thematic analysis. Six patients were interviewed, of whom four patients completed and two patients discontinued the exercise intervention. The mean (SD) age was 58 (9.7) years, the median disease duration was 10 years, and five patients were female. The analyses revealed seven themes that provided insight into perceptions and experiences: (1) ability to understand reasons for actions; (2) the need to be seen; (3) reaching their maximum effort; (4) experiencing their limits; (5) wanting personalized exercise therapy; (6) happy to be physically active; (7) benefits of exercise. Patients perceived that they were able to perform a cardiopulmonary exercise test with maximum effort and achieved the prescribed intensity of the exercise intervention. They also experienced an improvement in their physical activity by incorporating physical activity in their daily live. Overarching principles that re-occurred in the themes were: the need to be viewed as a person and the importance of feeling safe.

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

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

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

Background Studies of period changes in educational inequalities in mortality have shown important changes over time. It is unknown whether a birth cohort perspective paints the same picture. We compared changes in inequalities in mortality between a period and cohort perspective and explored mortality trends among low-educated and high-educated birth cohorts.Data and methods In 14 European countries, we collected and harmonised all-cause and cause-specific mortality data by education for adults aged 30–79 years in the period 1971–2015. Data reordered by birth cohort cover persons born between 1902 and 1976. Using direct standardisation, we calculated comparative mortality figures and resulting absolute and relative inequalities in mortality between low educated and high educated by birth cohort, sex and period.Results Using a period perspective, absolute educational inequalities in mortality were generally stable or declining, and relative inequalities were mostly increasing. Using a cohort perspective, both absolute and relative inequalities increased in recent birth cohorts in several countries, especially among women. Mortality generally decreased across successive birth cohorts among the high educated, driven by mortality decreases from all causes, with the strongest reductions for cardiovascular disease mortality. Among the low educated, mortality stabilised or increased in cohorts born since the 1930s in particular for mortality from cardiovascular diseases, lung cancer, chronic obstructive pulmonary disease and alcohol-related causes.Conclusions Trends in mortality inequalities by birth cohort are less favourable than by calendar period. In many European countries, trends among more recently born generations are worrying. If current trends among younger birth cohorts persist, educational inequalities in mortality may further widen. BACKGROUND: Studies of period changes in educational inequalities in mortality have shown important changes over time. It is unknown whether a birth cohort perspective paints the same picture. We compared changes in inequalities in mortality between a period and cohort perspective and explored mortality trends among low-educated and high-educated birth cohorts.DATA AND METHODS: In 14 European countries, we collected and harmonised all-cause and cause-specific mortality data by education for adults aged 30-79 years in the period 1971-2015. Data reordered by birth cohort cover persons born between 1902 and 1976. Using direct standardisation, we calculated comparative mortality figures and resulting absolute and relative inequalities in mortality between low educated and high educated by birth cohort, sex and period.RESULTS: Using a period perspective, absolute educational inequalities in mortality were generally stable or declining, and relative inequalities were mostly increasing. Using a cohort perspective, both absolute and relative inequalities increased in recent birth cohorts in several countries, especially among women. Mortality generally decreased across successive birth cohorts among the high educated, driven by mortality decreases from all causes, with the strongest reductions for cardiovascular disease mortality. Among the low educated, mortality stabilised or increased in cohorts born since the 1930s in particular for mortality from cardiovascular diseases, lung cancer, chronic obstructive pulmonary disease and alcohol-related causes.CONCLUSIONS: Trends in mortality inequalities by birth cohort are less favourable than by calendar period. In many European countries, trends among more recently born generations are worrying. If current trends among younger birth cohorts persist, educational inequalities in mortality may further widen.

Purpose Evidence for a hospital volume–outcome relationship in hip fracture surgery is inconclusive. This study aimed to analyze the association between hospital volume as a continuous parameter and several processes and outcomes of hip fracture care. Methods Adult patients registered in the nationwide Dutch Hip Fracture Audit (DHFA) between 2018 and 2020 were included. The association between annual hospital volume and turnaround times (time on the emergency ward, surgery Results In total, 43,258 patients from 68 hospitals were included. The median annual hospital volume was 202 patients [range 1–546]. Baseline characteristics did not differ with hospital volume. Provision of orthogeriatric co-treatment improved with higher volumes but decreased at > 367 patients per year (p Conclusion This is the first study analyzing the effect of hospital volume on hip fracture care, treating volume as a continuous parameter. Mortality and turnaround times showed no clinically relevant association with hospital volume. The provision of orthogeriatric co-treatment, however, increased with increasing volumes up to 367 patients per year, but decreased above this threshold. Future research on the effect of volume on complications and functional outcomes is indicated.

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.

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

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

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

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

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

Background The identification of dyadic subgroups of individuals living with dementia and their informal caregivers can help to design effective tailored support. In a previous German study, we identified six dementia dyad subgroups by applying Latent Class Analysis (LCA). Results showed sociodemographic heterogeneity as well as differences in health care outcomes (i.e., quality of life, health status, caregiver burden) between subgroups. The objective of this study is to determine if the dyad subgroups from the previous analysis can be replicated in a similar but distinct Dutch sample. Methods A LCA 3-step procedure was applied to baseline data from the COMPAS study, a prospective cohort study. LCA is a statistical approach used to identify heterogeneous subgroups within populations based on their pattern of answers on a set of categorical variables. Data comprises 509 community-living individuals with predominantly mild to moderate dementia and their informal caregivers. A narrative analysis was used to compare latent class structures of the original versus the replication study. Results Six distinct dementia dyad subgroups were identified: A subgroup of “adult–child-parent relation with younger informal caregiver” (31.8%), a “couple with female informal caregiver of older age” group (23.1%), an “adult–child-parent relation with middle-aged informal caregiver” group (14.2%), a “couple with middle-aged female informal caregiver” group (12.4%), a “couple with older male informal caregiver” group (11.2%) and a “couple with middle-aged male informal caregiver” group (7.4%). Quality of life of individuals with dementia was rated better in couples than in adult–child-relationships. Worst health for caregivers was reported by subgroups with female informal caregivers living together with male individuals with dementia in couple relationships. A subgroup with older female informal caregivers in couple relationships report the most severe burden on physical and mental health. In both studies, a model with six subgroups fitted the data best. Although substantive similarities between the subgroups of both studies appeared, considerable differences are also evident. Conclusion This replication study confirmed the existence of informal dementia dyad subgroups. The observed differences between the subgroups provide useful contributions for a more tailored health care services for informal caregivers and individuals living with dementia. Furthermore, it underlines the relevance of dyadic perspectives. To facilitate replication studies and increase the validity of evidence, a standardization of collected data across studies would be beneficial.

Background: Self-binding directives (SBDs) are psychiatric advance directives that include the possibility for service users to consent in advance to compulsory care in future mental health crises. Legal provisions for SBDs exist in the Netherlands since 2008 and were updated in 2020. While ethicists and legal scholars have identified several benefits and risks of SBDs, few data on stakeholder perspectives on SBDs are available. Aims: The aim of the study was to identify opportunities and challenges of SBDs perceived by stakeholders who have personal or professional experience with legally enforceable SBDs. Methods: Data collection was carried out in the Netherlands from February 2020 to October 2021 by means of semi-structured interviews. Participants were selected through purposive sampling and snowball methods. Interviews were conducted with mental health service users (n = 7), professionals (n = 13), and an expert on SBD policy (n = 1), resulting in a total number of 21 interviews. The data were analyzed thematically. Results: Perceived benefits of SBDs included increased autonomy, improvement of the therapeutic relationship, possibility of early intervention and prevention of harm, prevention of compulsory care, reduction of the duration of compulsory care and recovery, mitigation of negative experiences around compulsory care, and guidance for professionals in providing compulsory care. Perceived risks included infeasibility of SBD instructions, difficulty in decision-making around SBD activation, limited accessibility of SBDs, disappointment of service users due to non-compliance with SBDs, and limited evaluation and updating of SBD content. Barriers to SBD completion included lack of knowledge of SBDs among professionals, lack of motivation or insight among service users, and lack of professional support for SBD completion. Facilitators of SBD completion and activation included support for SBD completion, involvement of relatives and peer experts, specification of SBD content, and evaluation of compulsory care and SBD content. The new legal framework was regarded as having both positive and negative effects on SBD implementation. Conclusions: Stakeholders who have personal or professional experience with legally enforceable SBDs perceive SBDs as having important benefits and tend not to articulate the fundamental ethical concerns about SBDs which can be found in the ethics and legal literature. Instead, they perceive ethical and practical challenges that can be addressed through the implementation of suitable safeguards.

Background Between 2019 and 2021, the first Irish health system performance assessment (HSPA) framework was developed. As routinely collected health data are necessary to continuously populate indicators of an HSPA framework, a purpose-driven assessment of the health information system (HIS) in Ireland and its fitness to support the implementation of an HSPA framework was conducted. This study reports on the status of the Irish HIS through a multimethod assessment based on continuous broad stakeholder involvement. Methods Between May and November 2020, over 50 informants were engaged in individual and group interviews and stakeholder consultation workshops as part of the HIS assessment process. Descriptive themes and high-level data availability heatmaps were derived from interview and workshop data using thematic analysis. Indicator “passports” for the HSPA framework were populated during stakeholder consultation workshops and analysed using univariate descriptive statistics. Results The HIS in Ireland was able to provide administrative, survey and registry-based data for public sector acute care services, focusing on structure, process and output metrics. Significant data availability gaps, most notably from primary care, private hospitals and community care, were reported, with little availability of electronic health record and people-reported data. Data on outcome metrics were mostly missing, as were linkage possibilities across datasets for care pathway monitoring. The COVID-19 pandemic highlighted the national HIS’s shortcomings but also the capacity for rapid development and improvement. Conclusions A tailor-made assessment of the HIS in Ireland, involving a broad set of relevant stakeholders, revealed strengths, weaknesses and areas for improvement in the Irish health data landscape. It also contributed to the development of a national HSPA framework and momentum to further strengthen data infrastructure and governance, while working towards a more data-driven and person-centred healthcare system. This work demonstrates the utility of an inclusive HIS assessment process and is applicable beyond Ireland, where this case study was conducted.

Background Huntington’s disease is a complex neurodegenerative hereditary disease with symptoms in all domains of a person’s functioning. It begins after a healthy start in life and leads through the relentless progression over many years to complete care dependency and finally death. To date, the disease is incurable. The long progressive complex nature of the disease demands multiple disciplines for treatment and care of patient and family. These health care providers need inter- and multidisciplinary collaboration to persevere and be efficacious in this devastating disease trajectory. Discussion The position paper outlines current knowledge and experience alongside the experience and consensus of a recognised group of HD multidisciplinary experts. Additionally the patient’s voice is clear and calls for health care providers with a holistic view on patient and family. Building long-term trust is a cornerstone of the network around the patient. This paper describes a managed care network comprising all the needed professionals and services. In the health care system, the role of a central coordinator or case manager is of key importance but lacks an appropriate guideline. Other disciplines currently without guidelines are general practitioners, nurses, psychologists, and social workers. Guidelines for neurologists, psychiatrists, geneticists, occupational therapists, speech and language therapists, physiotherapists, dieticians, and dentists are being discussed. Apart from all these profession-specific guidelines, distinctive inter- and multidisciplinary collaboration requirements must be met. Conclusions and recommendations The complex nature of Huntington's disease demands multidisciplinary treatment and care endorsed by international regulations and the lay association. Available guidelines as reviewed in this paper should be used, made available by a central body, and updated every 3–5 years. Time needs to be invested in developing missing guidelines but the lack of this ‘proof’ should not prevent the ‘doing’ of good care.

Cytokines are regulators of the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the contribution of cytokine-secreting CD4+ and CD8+ memory T cells to the SARS-CoV-2-specific humoral immune response in immunocompromised kidney patients is unknown. Here, we profiled 12 cytokines after stimulation of whole blood obtained 28 days post second 100 μg mRNA-1273 vaccination with peptides covering the SARS-CoV-2 spike (S)-protein from patients with chronic kidney disease (CKD) stage 4/5, on dialysis, kidney transplant recipients (KTR), and healthy controls. Unsupervised hierarchical clustering analysis revealed two distinct vaccine-induced cytokine profiles. The first profile was characterized by high levels of T-helper (Th)1 (IL-2, TNF-α, and IFN-γ) and Th2 (IL-4, IL-5, IL-13) cytokines, and low levels of Th17 (IL-17A, IL-22) and Th9 (IL-9) cytokines. This cluster was dominated by patients with CKD, on dialysis, and healthy controls. In contrast, the second cytokine profile contained predominantly KTRs producing mainly Th1 cytokines upon re-stimulation, with lower levels or absence of Th2, Th17, and Th9 cytokines. Multivariate analyses indicated that a balanced memory T cell response with the production of Th1 and Th2 cytokines was associated with high levels of S1-specific binding and neutralizing antibodies mainly at 6 months after second vaccination. In conclusion, seroconversion is associated with the balanced production of cytokines by memory T cells. This emphasizes the importance of measuring multiple T cell cytokines to understand their influence on seroconversion and potentially gain more information about the protection induced by vaccine-induced memory T cells.

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

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

Objectives To investigate cartilage tissue turnover in response to a supervised 12-week exercise-related joint loading training program followed by a 6-month period of unsupervised training in patients with knee osteoarthritis (OA). To study the difference in cartilage tissue turnover between high- and low-resistance training. Method Patients with knee OA were randomized into either high-intensity or low-intensity resistance supervised training (two sessions per week) for 3 months and unsupervised training for 6 months. Blood samples were collected before and after the supervised training period and after the follow-up period. Biomarkers huARGS, C2M, and PRO-C2, quantifying cartilage tissue turnover, were measured by ELISA. Changes in biomarker levels over time within and between groups were analyzed using linear mixed models with baseline values as covariates. Results huARGS and C2M levels increased after training and at follow-up in both low- and high-intensity exercise groups. No changes were found in PRO-C2. The huARGS level in the high-intensity resistance training group increased significantly compared to the low-intensity resistance training group after resistance training (p = 0.029) and at follow-up (p = 0.003). Conclusion Cartilage tissue turnover and cartilage degradation appear to increase in response to a 3-month exercise-related joint loading training program and at 6-month follow-up, with no evident difference in type II collagen formation. Aggrecan remodeling increased more with high-intensity resistance training than with low-intensity exercise. These exploratory biomarker results, indicating more cartilage degeneration in the high-intensity group, in combination with no clinical outcome differences of the VIDEX study, may argue against high-intensity training.

Background Despite increasing use of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII, insulin pumps) in type 1 diabetes (T1D) in pregnancy, achieving recommended pregnancy glycaemic targets (3.5–7.8 mmol/L or 63–140 mg/dL) remains challenging. Consequently, the risk of adverse pregnancy outcomes remains high. Outside pregnancy, hybrid closed-loop (HCL) insulin delivery systems have led to a paradigm shift in the management of T1D, with 12% higher time in glucose target range (TIR) compared to conventional CSII. However, most commercially available HCL systems are currently not approved for use in pregnancy. This study aims to evaluate the efficacy, safety and cost-effectiveness of the MiniMed™ 780G HCL system (Medtronic) in T1D in pregnancy. Methods In this international, open-label, randomized controlled trial (RCT), we will compare the MiniMed™ 780G HCL system to standard of care (SoC) in T1D in pregnancy. Women aged 18–45 years with T1D diagnosis of at least one year, HbA1c ≤ 86 mmol/mol (≤ 10%), and confirmed singleton pregnancy up to 11 weeks 6 days will be eligible. After providing written informed consent, all participants will wear a similar CGM system (Guardian™ 3 or Guardian™ 4 CGM) during a 10-day run-in phase. After the run-in phase, participants will be randomised 1:1 to 780G HCL (intervention) or SoC [control, continuation of current T1D treatment with multiple daily injections (MDI) or CSII and any type of CGM] stratified according to centre, baseline HbA1c ( Discussion This large RCT will evaluate a widely used commercially available HCL system in T1D in pregnancy. Recruitment began in January 2021 and was completed in October 2022. Study completion is expected in May 2023. Trial registration ClinicalTrials.gov: NCT04520971. Registration date: August 20, 2020. https://clinicaltrials.gov/ct2/show/NCT04520971

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

BACKGROUND: Early P2Y12 inhibitor monotherapy has emerged as a promising alternative to 12 months of dual antiplatelet therapy following percutaneous coronary intervention (PCI). AIMS: In this single-arm pilot study, we evaluated the feasibility and safety of ticagrelor or prasugrel monotherapy directly following PCI in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). METHODS: Patients received a loading dose of ticagrelor or prasugrel before undergoing platelet function testing and subsequent PCI using new-generation drug-eluting stents. The stent result was adjudicated with optical coherence tomography in the first 35 patients. Ticagrelor or prasugrel monotherapy was continued for 12 months. The primary ischaemic endpoint was the composite of all-cause mortality, myocardial infarction, definite or probable stent thrombosis or stroke within 6 months. The primary bleeding endpoint was Bleeding Academic Research Consortium type 2, 3 or 5 bleeding within 6 months. RESULTS: From March 2021 to March 2022, 125 patients were enrolled, of whom 75 ultimately met all in- and exclusion criteria (mean age 64.5 years, 29.3% women). Overall, 70 out of 75 (93.3%) patients were treated with ticagrelor or prasugrel monotherapy directly following PCI. The primary ischaemic endpoint occurred in 3 (4.0%) patients within 6 months. No cases of stent thrombosis or spontaneous myocardial infarction occurred. The primary bleeding endpoint occurred in 7 (9.3%) patients within 6 months. CONCLUSIONS: This study provides first-in-human evidence that P2Y12 inhibitor monotherapy directly following PCI for NSTE-ACS is feasible, without any overt safety concerns, and highlights the need for randomised controlled trials comparing direct P2Y12 inhibitor monotherapy with the current standard of care.

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.

Background Malnutrition (i.e., protein-energy malnutrition) in older adults has severe negative clinical consequences, emphasizing the need for effective treatments. Many, often small, randomized controlled trials (RCTs) testing the effectiveness of nutritional interventions for the treatment of malnutrition showed mixed results and a need for meta-analyses and data pooling has been expressed. However, evidence synthesis is hampered by the wide variety of outcomes and their method of assessment in previous RCTs. This paper describes the protocol for developing a Core Outcome Set (COS) for nutritional intervention studies in older adults with malnutrition and those at risk. Methods The project consists of five phases. The first phase consists of a scoping review to identify frequently used outcomes in published RCTs and select additional patient-reported outcomes. The second phase includes a modified Delphi Survey involving experienced researchers and health care professionals working in the field of malnutrition in older adults, followed by the third phase consisting of a consensus meeting to discuss and agree what critical outcomes need to be included in the COS. The fourth phase will determine how each COS outcome should be measured based on a systematic literature review and a second consensus meeting. This will be followed by a dissemination and implementation phase. Patient and Public Involvement (PPI) representatives will contribute to study design, oversight, consensus, and dissemination. Conclusions The result of this project is a COS that should be included in any RCT evaluating the effect of nutritional interventions in older adults with malnutrition and those at risk. This COS will facilitate comparison of RCT results, will increase efficient use of research resources and will reduce bias due to measurement of the outcome and publication bias. Ultimately, the COS will support clinical decision making by identifying the most effective approaches for treating and preventing malnutrition in older adults.

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.

Contains fulltext : 291973.pdf (Publisher’s version ) (Open Access) OBJECTIVE: High psychological distress is reported by one third of colorectal cancer survivors (CRCS). However, intervention studies for CRCS have reported low participation rates. In this study, reasons for non-participation and low uptake in a psychological intervention trial were investigated. METHODS: CRCS were recruited for a randomized clinical trial on the efficacy of blended cognitive behavior therapy for psychological distress via databases, follow-up consultations, advertisements and an ongoing population-based study. The recruitment flow and reasons for non-participation were analyzed for patients recruited between 2016 and 2020. Subgroups were compared based on demographic, clinical and screening data. High distress as study entry criterion was measured with the Distress Thermometer (DT ≥ 5) and the problem list (PL). RESULTS: From all recruitment methods together, 1326 CRCS responded to the invitation letter of whom 510 (38%) were interested in receiving a screening questionnaire. Interested CRCS were significantly younger than non-interested CRCS (p

Objective: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and its predictors. Methods: Clinical data from 20 independent sites participating in the Global ECT-MRI Research Collaboration (GEMRIC) were obtained for analysis, totaling 500 patients with MDD (58.6 % women) with a mean age of 54.8 years. Severity of depression before and after ECT was assessed with validated depression scales. Remission was defined as a HAM-D score of 7 points or below after ECT. Variables associated with remission were selected based on literature (i.e. depression severity at baseline, age, duration of index episode, and presence of psychotic symptoms). Results: Remission rates of ECT were independent of sex, 48.0 % in women and 45.7 % in men (X2(1) = 0.2, p = 0.70). In the logistic regression analyses, a shorter index duration was identified as a sex-specific predictor for ECT outcome in women (X2(1) = 7.05, p = 0.01). The corresponding predictive margins did show overlapping confidence intervals for men and women. Conclusion: The evidence provided by our study suggests that ECT as a biological treatment for MDD is equally effective in women and men. A shorter duration of index episode was an additional sex- specific predictor for remission in women. Future research should establish whether the confidence intervals for the corresponding predictive margins are overlapping, as we find, or not.

Purpose: Older patients with COVID-19 can present with atypical complaints, such as falls or delirium. In other diseases, such an atypical presentation is associated with worse clinical outcomes. However, it is not known whether this extends to COVID-19. We aimed to study the association between atypical presentation of COVID-19, frailty and adverse outcomes, as well as the incidence of atypical presentation. Methods: We conducted a retrospective observational multi-center cohort study in eight hospitals in the Netherlands. We included patients aged ≥ 70 years hospitalized with COVID-19 between February 2020 until May 2020. Atypical presentation of COVID-19 was defined as presentation without fever, cough and/or dyspnea. We collected data concerning symptoms on admission, demographics and frailty parameters [e.g., Charlson Comorbidity Index (CCI) and Clinical Frailty Scale (CFS)]. Outcome data included Intensive Care Unit (ICU) admission, discharge destination and 30-day mortality. Results: We included 780 patients, 9.5% (n = 74) of those patients had an atypical presentation. Patients with an atypical presentation were older (80 years, IQR 76–86 years; versus 79 years, IQR 74–84, p = 0.044) and were more often classified as severely frail (CFS 6–9) compared to patients with a typical presentation (47.6% vs 28.7%, p = 0.004). Overall, there was no significant difference in 30-day mortality between the two groups in univariate analysis (32.4% vs 41.5%; p = 0.173) or in multivariate analysis [OR 0.59 (95% CI 0.34–1.0); p = 0.058]. Conclusions: In this study, patients with an atypical presentation of COVID-19 were more frail compared to patients with a typical presentation. Contrary to our expectations, an atypical presentation was not associated with worse outcomes.

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.

Contains fulltext : 290814.pdf (Publisher’s version ) (Open Access) Owing to the vulnerability of patients with chronic kidney disease to infectious diseases, the coronavirus disease 2019 (COVID-19) pandemic has been particularly devastating for the nephrology community. Unfortunately, the possibility of future COVID-19 waves or outbreaks of other infectious diseases with pandemic potential cannot be ruled out. The nephrology community made tremendous efforts to contain the consequences of the COVID-19 pandemic. Despite this, the COVID-19 pandemic has highlighted several shortcomings in our response to the pandemic and has taught us important lessons that can be utilized to improve our preparedness for any future health crises of a similar nature. In this article we draw lessons from the European Renal Association COVID-19 Database (ERACODA) project, a pan-European collaboration initiated in March 2020 to understand the prognosis of COVID-19 in patients on kidney function replacement therapy. We discuss the challenges faced in generating timely and robust evidence for informed management of patients with kidney disease and give recommendations for our preparedness for the next pandemic in Europe. Limited collaboration, the absence of common data architecture and the sub-optimal quality of available data posed challenges in our response to COVID-19. Aligning different research initiatives, strengthening electronic health records, and involving experts in study design and data analysis will be important in our response to the next pandemic. The European Renal Association may take a leading role in aligning research initiatives via its engagement with other scientific societies, national registries, administrators and researchers.

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

Summary: Hip fractures are associated with significant healthcare costs. In frail institutionalized patients, the costs of nonoperative management are less than operative management with comparable short-term quality of life. Nonoperative management of hip fractures in patients at the end of life should be openly discussed with SDM. Purpose: The aim was to describe healthcare use with associated costs and to determine cost-utility of nonoperative management (NOM) versus operative management (OM) of frail institutionalized older patients with a proximal femoral fracture. Methods: This study included institutionalized patients with a limited life expectancy aged ≥ 70 years who sustained a proximal femoral fracture in the Netherlands. Costs of hospital- and nursing home care were calculated. Quality adjusted life years (QALY) were calculated based on EuroQol-5D-5L utility scores at day 7, 14, and 30 and at 3 and 6 months. The incremental cost-effectiveness ratio (ICER) was calculated from a societal perspective. Results: Of the 172 enrolled patients, 88 (51%) patients opted for NOM and 84 (49%) for OM. NOM was associated with lower healthcare costs at 6 months (NOM; €2425 (SD 1.030), OM; €9325 (SD 4242), p < 0.001). The main cost driver was hospital stay (NOM; €738 (SD 841) and OM; €3140 (SD 2636)). The ICER per QALY gained in the OM versus NOM was €76,912 and exceeded the threshold of €20,000 per QALY. The gained QALY were minimal in the OM group in patients who died within 14- and 30-day post-injury, but OM resulted in more than triple the costs. Conclusion: OM results in significant higher healthcare costs, mainly due to the length of hospital stay. For frail patients at the end of life, NOM of proximal femoral fractures should be openly discussed in SDM conversations due to the limited gain in QoL. Trial registration. Netherlands Trial Register (NTR7245; date 10–06-2018).

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BACKGROUND: An urgent need exists to improve the suboptimal COVID-19 vaccine response in kidney transplant recipients (KTRs). We aimed to compare three alternative strategies with a control single dose mRNA-1273 vaccination: a double vaccine dose, heterologous vaccination, and temporary discontinuation of mycophenolate mofetil or mycophenolic acid.METHODS: This open-label randomised trial, done in four university medical centres in the Netherlands, enrolled KTRs without seroconversion after two or three doses of an mRNA vaccine. Between Oct 20, 2021, and Feb 2, 2022, 230 KTRs were randomly assigned block-wise per centre by a web-based system in a 1:1:1 manner to receive 100 μg mRNA-1273, 2 × 100 μg mRNA-1273, or Ad26.COV2-S vaccination. In addition, 103 KTRs receiving 100 μg mRNA-1273, were randomly assigned 1:1 to continue (mycophenolate mofetil+) or discontinue (mycophenolate mofetil-) mycophenolate mofetil or mycophenolic acid treatment for 2 weeks. The primary outcome was the percentage of participants with a spike protein (S1)-specific IgG concentration of at least 10 binding antibody units per mL at 28 days after vaccination, assessed in all participants who had a baseline measurement and who completed day 28 after vaccination without SARS-CoV-2 infection. Safety was assessed as a secondary outcome in all vaccinated patients by incidence of solicited adverse events, acute rejection or other serious adverse events. This trial is registered with ClinicalTrials.gov, NCT05030974 and is closed.FINDINGS: Between April 23, 2021, and July 2, 2021, of 12 158 invited Dutch KTRs, 3828 with a functioning kidney transplant participated in a national survey for antibody measurement after COVID-19 vaccination. Of these patients, 1311 did not seroconvert after their second vaccination and another 761 not even after a third. From these seronegative patients, 345 agreed to participate in our repeated vaccination study. Vaccination with 2 × mRNA-1273 or Ad26.COV2-S was not superior to single mRNA-1273, with seroresponse rates of 49 (68%) of 72 (95% CI 56-79), 46 (63%) of 73 (51-74), and 50 (68%) of 73 (57-79), respectively. The difference with single mRNA-1273 was -0·4% (-16 to 15; p=0·96) for 2 × mRNA-1273 and -6% (-21 to 10; p=0·49) for Ad26.COV2-S. Mycophenolate mofetil- was also not superior to mycophenolate mofetil+, with seroresponse rates of 37 (80%) of 46 (66-91) and 31 (67%) of 46 (52-80), and a difference of 13% (-5 to 31; p=0·15). Local adverse events were more frequent after a single and double dose of mRNA-1273 than after Ad26.COV2-S (65 [92%] of 71, 67 [92%] of 73, and 38 [50%] of 76, respectively; pINTERPRETATION: Repeated vaccination increases SARS-CoV-2-specific antibodies in KTRs, without further enhancement by use of a higher dose, a heterologous vaccine, or 2 weeks discontinuation of mycophenolate mofetil or mycophenolic acid. To achieve a stronger response, possibly required to neutralise new virus variants, repeated booster vaccination is needed.FUNDING: The Netherlands Organization for Health Research and Development and the Dutch Kidney Foundation.

Introduction: The association between obesity and outcome in critical illness is unclear. Since the amount of visceral adipose tissue(VAT) rather than BMI mediates the health effects of obesity we aimed to investigate the association between visceral obesity, BMI and 90-day mortality in critically ill patients. Method: In 555 critically ill patients (68% male), the VAT Index(VATI) was measured using Computed Tomography scans on the level of vertebra L3. The association between visceral obesity, BMI and 90-day mortality was investigated using univariable and multivariable analyses, correcting for age, sex, APACHE II score, sarcopenia and muscle quality. Results: Visceral obesity was present in 48.1% of the patients and its prevalence was similar in males and females. Mortality was similar amongst patients with and without visceral obesity (27.7% vs 24.0%, p = 0.31). The corrected odds ratio of 90-day mortality for visceral obesity was 0.667 (95%CI 0.424–1.049, p = 0.080). Using normal BMI as reference, the corrected odds ratio for overweight was 0.721 (95%CI 0.447–1.164 p = 0.181) and for obesity 0.462 (95%CI 0.208–1.027, p = 0.058). Conclusion: No significant association of visceral obesity and BMI with 90-day mortality was observed in critically ill patients, although obesity and visceral obesity tended to be associated with improved 90-day mortality.

Objectives: Clinical interpretability of the gait speed and 5-times sit-to-stand (5-STS) tests is commonly established by comparing older adults with and without self-reported mobility limitations (SRML) on gait speed and 5-STS performance, and estimating clinical cutpoints for SRML using the receiver operating characteristics (ROC) method. Accumulating evidence, however, suggests that the adjusted predictive modeling (APM) method may be more appropriate to estimate these interpretational cutpoints. Thus, we aimed to compare, in community-dwelling older adults, gait speed and 5-STS cutpoints estimated using the ROC and APM methods. Design: Cross-sectional study. Setting and Participants: This study analyzed data from 955 community-dwelling independently walking older adults (73%women) aged ≥60 years (mean, 68; range, 60–88). Methods: Participants completed the 10-metre gait speed and 5-STS tests. Participants were classified as having SRML if they responded "Yes" to either of the 2 questions regarding walking and stair climbing difficulty. Cutpoints for SRML and its component questions were estimated using ROC analysis with Youden criterion and the APM method. Results: The proportions of participants with self-reported walking difficulty, self-reported stair climbing difficulty, and SRML were 10%, 19%, and 22%, respectively. Gait speed and 5-STS time were moderately correlated with each other (r=-0.56) and with the self-reported measures (absolute r-values, 0.39–0.44). ROC-based gait speed cutpoints were 0.14 to 0.16 m/s greater than APM-based cutpoints (P < 0.05) whilst ROC-based 5-STS time cutpoints were 0.8 to 3.3 s lower than APM-based cutpoints (P < 0.05 for walking difficulty). Compared with ROC-based cutpoints, APM-based cutptoints were more precise and they varied monotonically with self-reported walking difficulty, self-reported stair climbing difficulty, and SRML. Conclusions and implications: In a sample of 955 older adults, our findings of precise and biologically plausible gait speed and 5-STS cutpoints for SRML estimated using the APM method indicate that this promising method could potentially complement or even replace traditional ROC methods.

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.

Background: The relationship between delirium and low levels of insulin-like growth factor 1 (IGF-1) is contradictory and uncertain. We hypothesised that low levels of IGF-1 are a predisposing factor for delirium in medical and abdominal surgical cohorts, in contrast to other surgical cohorts. Aims: Systematic review and meta-analysis investigating the association between peripheral levels of IGF-1 and delirium in medical and surgical patients to explore if there are distinct patterns of associations by using subgroup meta-analysis. Methods: PubMed, Scopus, CINAHL, Cochrane, and Embase databases were searched. Inclusion criteria were prospective studies in medical and surgical populations and available data. The following were collected: the setting (surgical/medical), the type (orthopaedic surgery, abdominal, cardiovascular, or medical), the number of participants, mean age, the number of delirious patients, scale/criteria for delirium, IGF-1 levels, and MMSE. Results: Thirteen studies were included and analysed. Low levels of IGF-1 are significantly associated with delirium in abdominal surgical samples and medical samples but not in the other surgical samples. Age, cognition, and the setting (medical vs. surgical) do not have any significant effect on the differences in IGF-1 levels between those with and without delirium. Discussion: Delirium in acute medical and abdominal surgery is triggered by low IGF-1 which may reflect chronic conditions like frailty/cachexia/sarcopenia, while in other surgeries perhaps from an inflammatory process. Conclusions: Low peripheral levels of IGF-1 are a predisposing factor for delirium only in acute medical and abdominal surgery. More studies are needed to confirm and to explore further this finding.

Improving parenting, child attachment, and externalizing behaviors: Meta-analysis of the first 25 randomized controlled trials on the effects of Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD). VIPP-SD combines support of parental sensitive responsiveness with coaching parents in sensitive limit setting. Here, we present meta-analyses of 25 RCTs conducted with more than 2,000 parents and caregivers. Parents or children had various risks. We examined its effectiveness in promoting parental cognitions and behavior regarding sensitive parenting and limit setting, in promoting secure child–parent attachment, and reducing externalizing child behavior. Web of Science, MEDLINE, PubMed, and recent reviews were searched for relevant trials (until May 10, 2021). Multilevel meta-analysis with META, METAFOR, and DMETAR in R took account of the 3-level structure of the datasets (studies, participants, measures). The meta-analyses showed substantial combined effect sizes for parenting behavior (r = .18) and attitudes (r = .16), and for child attachment security (r = .23), but not for child externalizing behavior (r = .07). In the subset of studies examining effects on both parenting and attachment, the association between effect sizes for parenting and for attachment amounted to r = .48. We consider the way in which VIPP-SD uses video-feedback an active intervention component. Whether VIPP-SD indeed stimulates secure attachment through enhanced positive parenting remains an outstanding question for further experimental study and individual participant data meta-analysis.

Purpose Antidepressants are well-established fall-risk increasing drugs (FRIDs) and therefore falls should be considered an important adverse drug event (ADE) of antidepressants. However, not all antidepressant users experience fall incidents and factors associated with increased fall risk among antidepressant users are incompletely understood. Our objective was to explore whether antidepressant plasma concentrations are associated with falls in older antidepressant users. Methods For this study, we included antidepressant users of the multicenter B-PROOF study. Fall incidents were recorded prospectively using fall calendars. Antidepressant plasma concentrations were analyzed by Liquid chromatography-mass spectrometry (LC–MS) at baseline and at 2 years follow-up. The associations between the observed antidepressant concentration and fall risk were assessed using Cox proportional hazard and logistic regression models and adjusted for potential confounders. Results In total 93 selective serotonin reuptake inhibitor (SSRI) and 41 antidepressant (TCA) users were identified. There was a significant association between baseline TCA plasma concentration and fall risk within users (HR 2.50, 95% CI 1.07–5.87, crude model). In the adjusted model, there were no significant associations between concentrations of SSRIs and fall risk. Conclusion There might be an association between plasma concentrations of TCAs and the risk of falling in older users. However, these results needs to be interpreted with caution considering the small sample size and accompanying limitation of confinement to crude analyses. Therefore, these novel findings need to replicated in a larger cohort, preferably including adjustment for potential confounders and more frequent measures of plasma concentrations is needed.

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.

Background The aim of this randomized, controlled trial is to determine whether antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin (COVIG) protects against severe coronavirus disease 2019 (COVID-19) in severely immunocompromised, hospitalized, COVID-19 patients. Methods Patients were randomly assigned to receive COVIG or intravenous immunoglobulin (IVIG) without SARS-CoV-2 antibodies. Results Severe COVID-19 was observed in 2 of 10 (20%) patients treated with COVIG compared to 7 of 8 (88%) in the IVIG control group (P = .015, Fisher’s exact test). Conclusions Antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin may be a valuable treatment in severely immunocompromised, hospitalized, COVID-19 patients and should be considered when no monoclonal antibody therapies are available.

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.