Association of longitudinal changes in patient-reported health status with return to work in the first 2 years after traumatic injury:A prospective cohort study in the Netherlands

OBJECTIVES: To determine the prognostic value of time driven changes in health status on return to work (RTW) in the first 2 years after traumatic injury. DESIGN: A prospective longitudinal cohort study. All patient-reported outcomes were measured at 1 week, 1, 3, 6, 12 and 24 months after injury. SETTING: Ten participating hospitals in the Netherlands. PARTICIPANTS: Employed adult clinical injury patients admitted to the hospital between August 2015 and November 2016 (N=1245 patients). MAIN OUTCOME MEASURES: Data about (first) RTW were used from the patient-reported questionnaires (1=yes, 0=no). RTW was measured as the first time a patient started working after hospital admission. Time until RTW was calculated in weeks. Health status was measured with the EuroQol Five Dimensions-3 Levels (EQ5D) including a dimension to measure cognition. RESULTS: At 24 months, 88.5% (n=1102) of the patients had returned to work. The median time to RTW was 6.6 weeks (IQR: 2–13). Patients’ health status was found to be an independent prognostic factor for RTW: a 0.1-unit increase in EQ5D (scale 0–1) translated into RTW being four times more likely (95% CI 1.60 to 11.94). Patients who had moderate or severe problems (0=no problems, 1=moderate or severe problems) with mobility (HR 0.91, 95% CI 0.84 to 0.98), anxiety/depression (HR 0.86, 95% CI 0.80 to 0.91), usual activities (HR 0.91, 95% CI 0.83 to 0.98), self-care (HR 0.90, 95% CI 0.79 to 0.99) and cognition (HR 0.90, 95% CI 0.85 to 0.94) were significantly less likely to RTW compared with patients with no problems. CONCLUSION: Increased self-reported health status over time is associated with a higher likelihood of RTW, independent of baseline risk factors, such as injury severity or education. Knowledge on patient-reported outcomes can contribute to the development of tailored RTW treatments. Furthermore, patient-reported outcomes could be used as monitoring tool to guide postinjury care in the clinical setting and RTW process. TRIAL REGISTRATION NUMBER: NCT02508675; Results

Prognostic factors for recovery of health status after injury: A prospective multicentre cohort study

Objectives To determine prognostic factors for health status and recovery patterns during the first 2 years after injury in the clinical trauma population. Design A prospective longitudinal cohort study. Setting Ten participating hospitals in Brabant, the Netherlands. Participants Injured adult patients admitted to a hospital between August 2015 and November 2016 were followed: 4883 (50%) patients participated. Main outcome measures Primary outcome was health status, measured with the EuroQol-5-dimensions-3-levels (EQ-5D), including a cognition item and the EuroQol Visual Analogue Scale. Health status was collected at 1 week, 1, 3, 6, 12 and 24 months after injury. Potential prognostic factors were based on literature and clinical experience (eg, age, sex, pre-injury frailty (Groningen Frailty Index), pre-injury EQ-5D). Results Health status increased mainly during the first 6 months after injury with a mean EQ-5D utility score at 1 week of 0.49 and 0.79 at 24 months. The dimensions mobility, pain/discomfort and usual activities improved up to 2 years after injury. Lower pre-injury health status, frailty and longer length of stay at the hospital were important prognostic factors for poor recovery. Spine injury, lower and upper extremity injury showed to be prognostic factors for problems after injury. Traumatic brain injury was a prognostic factor for cognitive problems. Conclusion This study contributes to the increase in knowledge of health recovery after injury. It could be a starting point to develop prediction models for specific injury classifications and implementation of personalised medicine. Trial registration number NCT02508675

The Ki-67 and Repoman mitotic phosphatases assemble via an identical, yet novel mechanism

Ki-67 and RepoMan have key roles during mitotic exit. Previously (Booth et al, eLife, 2014), we showed that Ki-67 organizes the mitotic chromosome periphery and recruits protein phosphatase 1 (PP1) to chromatin at anaphase onset, in a similar manner as RepoMan. Here we show how Ki-67 and RepoMan form mitotic exit phosphatases by recruiting PP1, how they distinguish between distinct PP1 isoforms and how the assembly of these two holoenzymes are dynamically regulated by Aurora B kinase during mitosis. Unexpectedly, our data also reveal that Ki-67 and RepoMan bind PP1 using an identical, yet entirely novel mechanism, interacting with a PP1 pocket that is engaged only by these two PP1 regulators. These findings not only show how two distinct mitotic exit phosphatases are recruited to their substrates, but also provides immediate opportunities for the design of novel cancer therapeutics that selectively target the Ki-67:PP1 and RepoMan:PP1 holoenzymes

Neuro-Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice

Aims: Mutations in DNA/RNA-binding factor (fused-in-sarcoma) FUS and superoxide dismutase-1 (SOD-1) cause amyotrophic lateral sclerosis (ALS). They were reproduced in SOD-1-G93A (SOD-1) and new FUS[1-359]-transgenic (FUS-tg) mice, where inflammation contributes to disease progression. The effects of standard disease therapy and anti-inflammatory treatments were investigated using these mutants. Methods: FUS-tg mice or controls received either vehicle, or standard ALS treatment riluzole (8 mg/kg/day), or anti-inflammatory drug a selective blocker of cyclooxygenase-2 celecoxib (30 mg/kg/day) for six weeks, or a single intracerebroventricular (i.c.v.) infusion of Neuro-Cells (a preparation of 1.39 × 106 mesenchymal and hemopoietic human stem cells, containing 5 × 105 of CD34+ cells), which showed anti-inflammatory properties. SOD-1 mice received i.c.v.-administration of Neuro-Cells or vehicle. Results: All FUS-tg-treated animals displayed less marked reductions in weight gain, food/water intake, and motor deficits than FUS-tg-vehicle-treated mice. Neuro-Cell-treated mutants had reduced muscle atrophy and lumbar motor neuron degeneration. This group but not celecoxib-FUS-tg-treated mice had ameliorated motor performance and lumbar expression of microglial activation marker, ionized calcium-binding adapter molecule-1 (Iba-1), and glycogen-synthase-kinase-3ß (GSK-3ß). The Neuro-Cells-treated-SOD-1 mice showed better motor functions than vehicle-treated-SOD-1 group. Conclusion: The neuropathology in FUS-tg mice is sensitive to standard ALS treatments and Neuro-Cells infusion. The latter improves motor outcomes in two ALS models possibly by suppressing microglial activation. © 2019 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons LtdWe thank ?5-100? Russian Excellence Program, Prof. Daniel C. Anthony, Diana Babayevskaya, and Arina Kosakova for their highly valuable contribution. ?Neuro-Cells? preparation was provided by Neuroplast BV, Maastricht, Netherlands

Diet-Quality Scores and the Risk of Type 2 Diabetes in Men

Objective: To 1) compare associations of diet-quality scores, which were inversely associated with cardiovascular disease, with incident type 2 diabetes and 2) test for differences in absolute-risk reduction across various strata. Research Design and Methods: Men from the Health Professionals Follow-Up Study, who were initially free of type 2 diabetes, cardiovascular disease, or cancer (n = 41,615), were followed for $\leq 20$ years. The Healthy Eating Index (HEI) 2005, the alternative HEI (aHEI) the Recommended Food Score, the alternative Mediterranean Diet (aMED) Score, and the Dietary Approaches to Stop Hypertension (DASH) Score were calculated from food-frequency questionnaires. Cox proportional hazard models with time-varying covariates were used to assess risk by quintiles and continuous intervals. Results: There were 2,795 incident cases of type 2 diabetes. After multivariate adjustment, the aHEI, aMED, and DASH scores were significantly associated with reduced risk. A 1-SD increase was associated with 9–13% reduced risk (P < 0.01), and the DASH score was associated with lower risk independent of other scores. These scores were associated with lower absolute risk among those who were overweight or obese compared with normal weight (P for interaction < 0.01). Conclusions: Several diet-quality scores were associated with a lower risk of type 2 diabetes and reflect a common dietary pattern characterized by high intakes of plant-based foods such as whole grains; moderate alcohol; and low intakes of red and processed meat, sodium, sugar-sweetened beverages, and trans fat. High-quality diets may yield the greatest reduction in diabetes cases when followed by those with a high BMI

Like Frying Multiple Eggs in One Pan: a Qualitative Study Exploring the Understanding of Inter-speciality Training in Cancer Care

High-quality cancer care is a key priority worldwide. Caring for people affected by cancer requires a range of specific knowledge, skills and experience to deliver the complex care regimens both within the hospital and within the community environment. In June 2022, the European Cancer Organisation along with 33 European cancer societies began working together to develop a curriculum for inter-speciality training for healthcare professionals across Europe. As part of the project, this research consisted of a qualitative survey distributed to the European Union societies via email. The aim of this paper is to disseminate the qualitative findings from healthcare professionals across Europe. Questionnaires were sent out to a convenience sample of 219 healthcare professionals and patient advocates with a response rate of 55% (n = 115). The findings identified that there were four key themes: 'What is inter-speciality training?', 'Barriers and challenges', 'Support throughout the cancer journey' and 'New ways of working'. These results are part of a larger needs analysis and scoping review to inform the development of a core competency framework which will be part of an inter-speciality curriculum for specialist cancer doctors, nurses and other healthcare professionals across Europe. Healthcare professionals will be able to access education and training through the virtual learning environment and workshops and by clinical rotations to other specialties

Clustering of health and risk behaviour in immigrant and indigenous Dutch residents aged 19–40 years

Objectives\ud Studies on the co-occurrence, ‘clustering’ of health and other risk behaviours among immigrants from non-industrialised countries lack until now. The aim of this study was to compare this clustering in immigrant and indigenous adults.\ud \ud Methods\ud A representative sample (N = 2,982; response 71%) of the Dutch population aged 19–40, with 247 respondents from non-industrialized countries (Turkey, Morocco, Surinam, Netherlands Antilles), was asked about health behaviours (alcohol, smoking, drugs, unsafe sex, exercise, nutrition, sleep behaviour, traffic behaviour), and about rule-breaking behaviour and aggression. Data were collected using internet questionnaires, which excluded respondents unable to read Dutch.\ud \ud Results\ud Among indigenous adults, health and risk behaviours co-occur in three clusters (alcohol, health-enhancing behaviour, and rule-breaking behaviour), whereas among immigrant groups two clusters were found (alcohol and rule-breaking behaviour/smoking). Differences mostly concerned health-enhancing behaviours such as nutrition, which was not part of any cluster, and physical activity.\ud \ud Conclusions\ud This supports an integrated promotion of healthier lifestyles to immigrants who are able to read Dutch. Regarding potentially risky behaviours like alcohol use and rule-breaking behaviours, this could be similar to that for indigenous people\u

Effects of supplemented isoenergetic diets varying in cereal fiber and protein content on the bile acid metabolic signature and relation to insulin resistance

Bile acids (BA) are potent metabolic regulators influenced by diet. We studied effects of isoenergetic increases in the dietary protein and cereal-fiber contents on circulating BA and insulin resistance (IR) in overweight and obese adults. Randomized controlled nutritional intervention (18 weeks) in 72 non-diabetic participants (overweight/obese: 29/43) with at least one further metabolic risk factor. Participants were group-matched and allocated to four isoenergetic supplemented diets: control; high cereal fiber (HCF); high-protein (HP); or moderately increased cereal fiber and protein (MIX). Whole-body IR and insulin-mediated suppression of hepatic endogenous glucose production were measured using euglycaemic–hyperinsulinemic clamps with [6-62H2] glucose infusion. Circulating BA, metabolic biomarkers, and IR were measured at 0, 6, and 18 weeks. Under isoenergetic conditions, HP-intake worsened IR in obese participants after 6 weeks (M-value: 3.77 ± 0.58 vs. 3.07 ± 0.44 mg/kg/min, p = 0.038), with partial improvement back to baseline levels after 18 weeks (3.25 ± 0.45 mg/kg/min, p = 0.089). No deleterious effects of HP-intake on IR were observed in overweight participants. HCF-diet improved IR in overweight participants after 6 weeks (M-value 4.25 ± 0.35 vs. 4.81 ± 0.31 mg/kg/min, p = 0.016), but did not influence IR in obese participants. Control and MIX diets did not influence IR. HP-induced, but not HCF-induced changes in IR strongly correlated with changes of BA profiles. MIX-diet significantly increased most BA at 18 weeks in obese, but not in overweight participants. BA remained unchanged in controls. Pooled BA concentrations correlated with fasting fibroblast growth factor-19 (FGF-19) plasma levels (r = 0.37; p = 0.003). Higher milk protein intake was the only significant dietary predictor for raised total and primary BA in regression analyses (total BA, p = 0.017; primary BA, p = 0.011). Combined increased intake of dietary protein and cereal fibers markedly increased serum BA concentrations in obese, but not in overweight participants. Possible mechanisms explaining this effect may include compensatory increases of the BA pool in the insulin resistant, obese state; or defective BA transport