Associations between physical activity, physical fitness, and body composition in adults living in Germany: A cross-sectional study.

BACKGROUND & AIMS: Body composition (BC) changes with age and is associated with morbidity and mortality. A physically active lifestyle influences BC and represents an important predictor of successful aging. To emphasize this, the World Health Organization established activity recommendations for all age groups. We describe BC during adulthood using a cross-sectional sample from a German community and investigate the associations between physical activity (PA), physical fitness (PF), and BC. METHODS: Data from 329 men and women aged 35 to 86 years were analyzed. PA was measured by questionnaire and classified into sport activity and habitual activity. PF was measured through physical performance tests and BC by bioelectrical impedance analysis. Fat mass index (FMI) and fat-free mass index (FFMI) were calculated to represent height-adjusted BC. Associations between PA, PF, and BC were analyzed using linear regression models. RESULTS: For both sexes, strength was positively associated with FFMI (♂: ß = 0.313; ♀: ß = 0.213) and phase angle (♂: ß = 0.357; ♀: ß = 0.409). For FMI, a significant negative association with strength was found only in women (ß = -0.189). Cardiorespiratory fitness showed a negative association with FMI (ß = -0.312) and FFMI (ß = -0.201) for men, while in women a positive association was found for FFMI (ß = 0.186). For coordination, a significant association with FMI was observed only in women (ß = -0.190). Regarding PA only one significant relationship between sport activity and FMI among women (ß = -0.170) was found. CONCLUSIONS: In our sample, PF was closer related to BC than PA. Strength and cardiorespiratory fitness were the strongest predictors for BC. This supports the World Health Organization's activity recommendations to include both resistance and endurance training in the weekly sports program to maintain a healthy BC.

Cell Line Development Using Targeted Gene Integration into MAR-Rich Landing Pads for Stable Expression of Transgenes.

Integration of a gene of interest (GOI) into the genome of mammalian cells is the first step of cell line development campaigns for the production of biotherapeutics. Besides random integration methods, targeted gene integration approaches have emerged as promising tools over the last few years. In addition to reducing heterogeneity within a pool of recombinant transfectants, this process can also facilitate shorter timelines of the current cell line development process. Herein, we describe protocols for generating host cell lines carrying matrix attachment region (MAR)-rich landing pads (LPs), including BxB1 recombination sites. These LP-containing cell lines allow for site-specific and simultaneous integration of multiple GOIs. The resulting transgene-expressing stable recombinant clones can be used for the production of mono- or multispecific antibodies.

Longitudinal associations between physical activity and five risk factors of metabolic syndrome in middle-aged adults in Germany.

BACKGROUND: We examined the longitudinal association between (change in) physical activity (PA) with new onset of five risk factors of metabolic syndrome among 657 middle-aged adults (mean age 44.1 (standard deviation (SD) 8.6) years) who were free of the respective outcome at baseline, in a longitudinal cohort study spanning over 29 years. METHODS: Levels of habitual PA and sports-related PA were assessed by a self-reported questionnaire. Incident elevated waist circumference (WC), elevated triglycerides (TG), reduced high-density lipoprotein cholesterols (HDL), elevated blood pressure (BP), and elevated blood-glucose (BG) were assessed by physicians and by self-reported questionnaires. We calculated Cox proportional hazard ratio regressions and 95% confidence intervals. RESULTS: Over time, participants developed (cases of incident risk factor; mean (SD) follow-up time) elevated WC (234 cases; 12.3 (8.2) years), elevated TG (292 cases; 11.1 (7.8) years), reduced HDL (139 cases; 12.4 (8.1) years), elevated BP (185 cases; 11.4 (7.5) years), or elevated BG (47 cases; 14.2 (8.5) years). For PA variables at baseline, risk reductions ranging between 37 and 42% for reduced HDL levels were detected. Furthermore, higher levels of PA (≥ 16.6 METh per week) were associated with a 49% elevated risk for incident elevated BP. Participants who increased PA levels over time, had risk reductions ranging between 38 and 57% for elevated WC, elevated TG and reduced HDL. Participants with stable high amounts of PA from baseline to follow-up had risk reductions ranging between 45 and 87% for incident reduced HDL and elevated BG. CONCLUSIONS: PA at baseline, starting PA engagement, maintaining and increasing PA level over time are associated with favorable metabolic health outcomes.

Comparison of two automated oxygen controllers in oxygen targeting in preterm infants during admission: an observational study.

OBJECTIVE: To compare the effect of two different automated oxygen control devices on time preterm infants spent in different oxygen saturation (SpO2) ranges during their entire stay in the neonatal intensive care unit (NICU). DESIGN: Retrospective cohort study of prospectively collected data. SETTING: Tertiary level neonatal unit in the Netherlands. PATIENTS: Preterm infants (OxyGenie 75 infants, CLiO2 111 infants) born at 24-29 weeks' gestation receiving at least 72 hours of respiratory support between October 2015 and November 2020. INTERVENTIONS: Inspired oxygen concentration was titrated by the OxyGenie controller (SLE6000 ventilator) between February 2019 and November 2020 and the CLiO2 controller (AVEA ventilator) between October 2015 and December 2018 as standard of care. MAIN OUTCOME MEASURES: Time spent within SpO2 target range (TR, 91-95% for either epoch) and other SpO2 ranges. RESULTS: Time spent within the SpO2 TR when receiving supplemental oxygen was higher during OxyGenie control (median 71.5 [IQR 64.6-77.0]% vs 51.3 [47.3-58.5]%, p<0.001). Infants under OxyGenie control spent less time in hypoxic and hyperoxic ranges (SpO2<80%: 0.7 [0.4-1.4]% vs 1.2 [0.7-2.3]%, p<0.001; SpO2>98%: 1.0 [0.5-2.4]% vs 4.0 [2.0-7.9]%, p<0.001). Both groups received a similar FiO2 (29.5 [28.0-33.2]% vs 29.6 [27.7-32.1]%, p=not significant). CONCLUSIONS: Oxygen saturation targeting was significantly different in the OxyGenie epoch in preterm infants, with less time in hypoxic and hyperoxic SpO2 ranges during their stay in the NICU.

Family predictors of physical activity change during the COVID-19 lockdown in preschool children in Germany.

The COVID-19 pandemic is associated with crucial changes in children's daily life including their physical activity (PA) and screen time (ST). Among preschool children, the family represents an important factor for sufficient PA levels by being the gatekeeper for PA. Thus, the aim of this study was to investigate the influence of the family environment, specifically SES, parental support, and having siblings on COVID-19-related changes of PA and ST behavior in 317 (170 boys, 147 girls) German preschool children using longitudinal data. Our results indicate a decline in total amount of sports-related PA, an increase in outdoor play, as well as an increase in leisure ST in preschool children. The changes in total amount of PA differed between children with different levels of parental support as well as in dependence on having siblings. Furthermore, levels of outdoor play and ST in preschool children were influenced by environmental factors like having access to their own garden. We conclude that the family environment (parental support as well as physical environment) is highly relevant for PA and ST levels in preschool children. To provide every child with PA opportunities during potential future lockdowns, restriction policies should be adapted and parents need sophisticated information about the importance of their support and thus the PA levels of their children.

Clinical outcomes of preterm infants while using automated controllers during standard care: comparison of cohorts with different automated titration strategies.

OBJECTIVE: To compare short-term clinical outcome after using two different automated oxygen controllers (OxyGenie and CLiO2). DESIGN: Propensity score-matched retrospective observational study. SETTING: Tertiary-level neonatal unit in the Netherlands. PATIENTS: Preterm infants (OxyGenie n=121, CLiO2 n=121) born between 24+0-29+6 weeks of gestation. Median (IQR) gestational age in the OxyGenie cohort was 28+3 (26+3.5-29+0) vs 27+5 (26+5-28+3) in the CLiO2 cohort, respectively 42% and 46% of infants were male and mean (SD) birth weight was 1034 (266) g vs 1022 (242) g. INTERVENTIONS: Inspired oxygen was titrated by OxyGenie (SLE6000) or CLiO2 (AVEA) during respiratory support. MAIN OUTCOME MEASURES: Mortality, retinopathy of prematurity (ROP), bronchopulmonary dysplasia and necrotising enterocolitis. RESULTS: Fewer infants in the OxyGenie group received laser coagulation for ROP (1 infant vs 10; risk ratio 0.1 (95% CI 0.0 to 0.7); p=0.008), and infants stayed shorter in the neonatal intensive care unit (NICU) (28 (95% CI 15 to 42) vs 40 (95% CI 25 to 61) days; median difference 13.5 days (95% CI 8.5 to 19.5); p<0.001). Infants in the OxyGenie group had fewer days on continuous positive airway pressure (8.4 (95% CI 4.8 to 19.8) days vs 16.7 (95% CI 6.3 to 31.1); p<0.001) and a significantly shorter days on invasive ventilation (0 (95% CI 0 to 4.2) days vs 2.1 (95% CI 0 to 8.4); p=0.012). There were no statistically significant differences in all other morbidities. CONCLUSIONS: In this propensity score-matched retrospective study, the OxyGenie epoch was associated with less morbidity when compared with the CLiO2 epoch. There were significantly fewer infants that received treatment for ROP, received less intensive respiratory support and, although there were more supplemental oxygen days, the duration of stay in the NICU was shorter. A larger study will have to replicate these findings.

Physical Activity and Recurrent Pain in Children and Adolescents in Germany-Results from the MoMo Study.

Recurrent pain can be a significant disruption in the activities of daily life, and is not only a health problem in adults but also in children and adolescents. This study analyzed the prevalence of recurrent pain in the current sample (n = 1516; 11-17 years (meanage = 14.4 ± 2.0 years); 50.8% female) of a nationwide study in Germany, evaluated the association of participants' device-based physical activity (PA) with the prevalence of recurrent pain, and assessed whether children and adolescents who reported pain for the last three months accumulated less PA than those who did not. A higher prevalence was found in girls for recurrent headaches (42.2% vs. 28.7%), abdominal pain (28.2% vs. 20.1%), and back pain (26.9% vs. 19.5%). We found higher odds for recurrent headaches in girls (OR = 1.54) and in participants that did not reach at least 60 min of moderate to vigorous PA (MVPA) per day (OR = 2.06). Girls who reported recurrent headaches accumulated 4.7 min less MVPA per day than those without. The prevalence of pain remains at a high level in the German youth and underscores the need for interventions to improve the health situations of children and adolescents.

Longitudinal association between physical activity and the risk of incident metabolic syndrome in middle-aged adults in Germany.

We examined the longitudinal association between physical activity (PA) and the risk of incident metabolic syndrome (MetS) among middle-aged, community-dwelling adults, including 591 individuals (314 females; mean (SD) age, 43.8 (8.5) years) who were free of MetS at baseline. Habitual and sports-related PA was assessed by a self-reported questionnaire. MetS was defined based on HDL-cholesterols, triglycerides, glucose or HbA1c, blood pressure, and waist circumference. We calculated Cox proportional hazard ratios (HR) and 95% confidence intervals (CI) using regression analyses. Over a mean follow-up of 12.5 years, 205 participants developed incident MetS. Four different sports-related PA measures were associated with a decreased risk of incident MetS: (1) Engaging in ≥ 75 min/week (HR 0.71, 95% CI 0.53-0.94), (2) maintaining a continuously high amount from baseline to follow-up of ≥ 75 min/week (HR 0.66, 95% CI 0.46-0.94), (3) starting from < 150 min/week at baseline to ≥ 150 min/week at follow-up (HR 0.65, 95% CI 0.45-0.94), and (4) increasing from < 16.6 MET-hours/week at baseline to ≥ 16.6 MET-hours/week at follow-up (HR 0.47, 95% CI 0.31-0.71). Thus, maintaining, starting or increasing sports-related PA is associated with a lower risk of incident MetS.

Communication, perception, and use of personalized side-effect risks in prostate cancer treatment-decision making: An observational and interview study.

OBJECTIVE: We investigated how healthcare professionals (HPs) communicate personalized risks of treatment side-effects to patients with localized prostate cancer during consultations, and explored how these patients perceive and use such risks during treatment decision-making. METHODS: Patient consultations with nurse practitioners and urologists discussing personalized risks of urinary incontinence after prostatectomy were audiotaped, transcribed, and coded. Patients (n = 27) were then interviewed to explore their perceptions and use of personalized side-effect risks. RESULTS: HPs explained personalized risks by discussing risk factors, which was appreciated and recalled by patients. Personalized risks were typically communicated both numerically and verbally (70%). When using numbers, HPs always used percentages, but rarely used natural frequencies (14%). Uncertainty was disclosed in only 34% of consultations. One-third of patients used personalized risks in their treatment decision-making by either switching to another treatment or sticking to their initial preference. CONCLUSIONS: Patients value and use personalized side-effect risks during treatment decision-making. Clearly explaining the relationship between risk factors and personalized risk estimates may help patients understand and recall those. Practice implications HPs should not only give patients specific and precise numerical risk information, but should also put effort in explaining how the personalized side-effect risks are determined.

Generation of a host cell line containing a MAR-rich landing pad for site-specific integration and expression of transgenes.

In recent years, targeted gene integration (TI) has been introduced as a strategy for the generation of recombinant mammalian cell lines for the production of biotherapeutics. Besides reducing the immense heterogeneity within a pool of recombinant transfectants, TI also aims at shortening the duration of the current cell line development process. Here we describe the generation of a host cell line carrying Matrix-Attachment Region (MAR)-rich landing pads (LPs), which allow for the simultaneous and site-specific integration of multiple genes of interest (GOIs). We show that several copies of each chicken lysozyme 5'MAR-based LP containing either BxB1 wild type or mutated recombination sites, integrated at one random chromosomal locus of the host cell genome. We further demonstrate that these LP-containing host cell lines can be used for the site-specific integration of several GOIs and thus, generation of transgene-expressing stable recombinant clones. Transgene expression was shown by site-specific integration of heavy and light chain genes coding for a monospecific antibody (msAb) as well as for a bi-specific antibody (bsAb). The genetic stability of the herein described LP-based recombinant clones expressing msAb or bsAb was demonstrated by cultivating the recombinant clones and measuring antibody titers over 85 generations. We conclude that the host cell containing multiple copies of MAR-rich landing pads can be successfully used for stable expression of one or several GOIs.

Comparison of two devices for automated oxygen control in preterm infants: a randomised crossover trial.

OBJECTIVE: To compare the effect of two different automated oxygen control devices on target range (TR) time and occurrence of hypoxaemic and hyperoxaemic episodes. DESIGN: Randomised cross-over study. SETTING: Tertiary level neonatal unit in the Netherlands. PATIENTS: Preterm infants (n=15) born between 24+0 and 29+6 days of gestation, receiving invasive or non-invasive respiratory support with oxygen saturation (SpO2) TR of 91%-95%. Median gestational age 26 weeks and 4 days (IQR 25 weeks 3 days-27 weeks 6 days) and postnatal age 19 (IQR 17-24) days. INTERVENTIONS: Inspired oxygen concentration was titrated by the OxyGenie controller (SLE6000 ventilator) and the CLiO2 controller (AVEA ventilator) for 24 hours each, in a random sequence, with the respiratory support mode kept constant. MAIN OUTCOME MEASURES: Time spent within set SpO2 TR (91%-95% with supplemental oxygen and 91%-100% without supplemental oxygen). RESULTS: Time spent within the SpO2 TR was higher during OxyGenie control (80.2 (72.6-82.4)% vs 68.5 (56.7-79.3)%, p<0.005). Less time was spent above TR while in supplemental oxygen (6.3 (5.1-9.9)% vs 15.9 (11.5-30.7)%, p<0.005) but more time spent below TR during OxyGenie control (14.7 (11.8%-17.2%) vs 9.3 (8.2-12.6)%, p<0.05). There was no significant difference in time with SpO2 <80% (0.5 (0.1-1.0)% vs 0.2 (0.1-0.4)%, p=0.061). Long-lasting SpO2 deviations occurred less frequently during OxyGenie control. CONCLUSIONS: The OxyGenie control algorithm was more effective in keeping the oxygen saturation within TR and preventing hyperoxaemia and equally effective in preventing hypoxaemia (SpO2 <80%), although at the cost of a small increase in mild hypoxaemia. TRIAL REGISTRY NUMBER: NCT03877198.

Removal of patient-specific reconstruction plates after mandible reconstruction with a fibula free flap: is the plate the problem?

Computer-aided microvascular mandible reconstruction is an increasingly common procedure in oral and maxillofacial surgery. The aim of this retrospective single-centre study was to evaluate the rate and specifics of hardware removal after fibula free flap (FFF) fixation with a patient-specific reconstruction plate. The study included patients who underwent hardware removal between April 2017 and October 2019. Statistical analyses were performed regarding the different indications for plate removal (dental implantation versus complication) and the surgical approach (intraoral versus extraoral). Plate removal was performed in 29 of 98 patients (29.6%) after FFF fixation with a patient-specific reconstruction plate. Plate removal was done prior to dental implantation in 58.6% of cases and due to complications in 41.4%. Complications seen between reconstructive surgery and plate removal were less frequent in the dental rehabilitation group (8/17 vs 12/12; P=0.002). Within this group, 35.3% of plates were removed intraorally, and the majority of partial plate removals were performed in the patients with plate removal for dental rehabilitation (72.7% vs 27.3%). Hospitalization was shorter with an intraoral approach (1.7 days vs 4.0 days, P=0.052). The removal of patient-specific reconstruction plates prior to dental implantation is often partial and can be performed intraorally. The use of patient-specific miniplates for fixation of FFF might facilitate later dental rehabilitation.

Antibody display technologies: selecting the cream of the crop.

Antibody display technologies enable the successful isolation of antigen-specific antibodies with therapeutic potential. The key feature that facilitates the selection of an antibody with prescribed properties is the coupling of the protein variant to its genetic information and is referred to as genotype phenotype coupling. There are several different platform technologies based on prokaryotic organisms as well as strategies employing higher eukaryotes. Among those, phage display is the most established system with more than a dozen of therapeutic antibodies approved for therapy that have been discovered or engineered using this approach. In recent years several other technologies gained a certain level of maturity, most strikingly mammalian display. In this review, we delineate the most important selection systems with respect to antibody generation with an emphasis on recent developments.

Association Between Sense of Coherence and Health Outcomes at 10 and 20 Years Follow-Up: A Population-Based Longitudinal Study in Germany.

Background: The sense of coherence (SOC) is reported to influence health, but health may also have an impact on SOC. The objective of this study was to examine the longitudinal associations between SOC and selected self-reported and physician-assessed health outcomes over a period of 10 and 20 years and to determine the predominant direction of the associations. Methods: We conducted a population-based, longitudinal study, involving 392 participants (188 females and 204 males; mean age 43.01 years) who were followed for a median of 10 and 18 years. Analyses of variance were carried out to examine the longitudinal associations between SOC at baseline and health outcomes (i.e., self-rated health status, SHS; physical health status assessed by a physician, PHS; self-reported satisfaction with life, SWL) at follow-ups. The direction of associations was examined using a cross-lagged model on correlation coefficients. Results: There were significant group effects for SOC at baseline on SHS at 20-year follow-up (F = 4.09, p = 0.018, ηp2 = 0.041), as well as on SWL at 10-year (F = 12.67, p < 0.01, ηp2 = 0.072) and at 20-year follow-up (F = 8.09, p < 0.1, ηp2 = 0.069). SHS (r = 0.238, p < 0.01), PHS (r = -0.140, p < 0.05) and SWL (r = 0.400, p < 0.01) predicted SOC at 10-year follow-up stronger than vice versa. The direction of associations between SOC and health parameters at 20-year follow-up was less consistent. Conclusions: The long-term associations between SOC and self-reported and physician-assessed health may be reciprocal in community-dwelling adults. More research is needed to examine the predictive power of health on SOC and whether interventions targeted at improving health parameters, may impact SOC.

A latent-class heteroskedastic hurdle trajectory model: patterns of adherence in obstructive sleep apnea patients on CPAP therapy.

BACKGROUND: Sleep apnea patients on CPAP therapy exhibit differences in how they adhere to the therapy. Previous studies have demonstrated the benefit of describing adherence in terms of discernible longitudinal patterns. However, these analyses have been done on a limited number of patients, and did not properly represent the temporal characteristics and heterogeneity of adherence. METHODS: We illustrate the potential of identifying patterns of adherence with a latent-class heteroskedastic hurdle trajectory approach using generalized additive modeling. The model represents the adherence trajectories on three aspects over time: the daily hurdle of using the therapy, the daily time spent on therapy, and the day-to-day variability. The combination of these three characteristics has not been studied before. RESULTS: Applying the proposed model to a dataset of 10,000 patients in their first three months of therapy resulted in nine adherence groups, among which 49% of patients exhibited a change in adherence over time. The identified group trajectories revealed a non-linear association between the change in the daily hurdle of using the therapy, and the average time on therapy. The largest difference between groups was observed in the patient motivation score. The adherence patterns were also associated with different levels of high residual AHI, and day-to-day variability in leakage. CONCLUSION: The inclusion of the hurdle model and the heteroskedastic model into the mixture model enabled the discovery of additional adherence patterns, and a more descriptive representation of patient behavior over time. Therapy adherence was mostly affected by a lack of attempts over time, suggesting that encouraging these patients to attempt therapy on a daily basis, irrespective of the number of hours used, could drive adherence. We believe the methodology is applicable to other domains of therapy or medication adherence.

A Short Version of the Physical Activity Enjoyment Scale: Development and Psychometric Properties.

OBJECTIVE: The purposes of this paper were to (a) develop a new short, theory-driven, version of the physical activity enjoyment scale (PACES-S) using content analysis; and (b) subsequently to measure the psychometric properties (construct validity, internal consistency, test-retest reliability, and concurrent validity) of the PACES-S for adolescents. METHODS: Six experts used a four-point Likert scale to assess the content validity of each of the 16 items of the physical activity enjoyment scale according to a provided definition of physical activity enjoyment. Based on the results, exploratory factor analysis was used to analyze survey data from a longitudinal study of 182 individuals (Measure 1 of Study 1: 15.75 ± 3.39 yrs; 56.6% boys, 43.4% girls), and confirmatory factor analysis (Measure 2 of Study 1: 15.69 ± 3.44 yrs; 56.3% boys, 43.7% girls) was used to analyze the survey data from a cross-sectional study of 3219 individuals (Study 2; 15.99 ± 3.10 yrs; 47.8% boys, 52.2% girls) to assess the construct validity of the new measure. To assess the reliability, test-retest reliability was assessed in Study 1 and internal consistency in Study 1 and 2. For the concurrent validity, correlations with self-reported and device-based physical activity behavior were assessed in both studies. RESULTS: Four out of sixteen items were selected for PACES-S. Exploratory factor analysis and confirmatory factor analyses identified and supported its factorial validity (χ2 = 53.62, df = 2, p < 0.001; RMSEA = 0.073; CFI = 0.99; RFI = 0.96; NFI = 0.99; TLI = 0.96; IFI = 0.99). Results showed good test-retest reliability (r = 0.76) and internal consistency (a = 0.82 to 0.88). Regarding concurrent validity, the results showed positive correlations with a physical activity questionnaire (Study 1: r = 0.36), with a physical activity diary (Study 1: r = 0.44), and with accelerometer-recorded data (Study 1: r = 0.32; Study 2: r = 0.21). CONCLUSIONS: The results indicate that PACES-S is a reliable and valid instrument that may be particularly useful to measure physical activity enjoyment in large-scale studies. It shows comparable measurement properties as the long version of PACES.

Indicators to Assess Physical Health of Children and Adolescents in Activity Research-A Scoping Review.

Sufficient physical activity can help promote and maintain health, while its lack can jeopardize it. Since health and physical activity lay their foundation for later life in childhood and adolescence, it is important to examine this relationship from the beginning. Therefore, this scoping review aims to provide an overview of physical health indicators in children and adolescents in research on the effects of physical activity and sedentary behavior. We identified the indicators used to quantify or assess physical health and summarized the methods used to measure these indicators. We systematically searched Scopus, Pubmed, and Web of Science databases for systematic reviews. The search yielded 4595 records from which 32 records were included in the review. The measurements for physical health reported in the reviews contained measures of body composition, cardiometabolic biomarkers, physical fitness, harm/injury, or bone health. Body composition was the most used indicator to assess and evaluate physical health in children, whereas information on harm and injury was barely available. In future research longitudinal studies are mandatory to focus on the prospective relationships between physical activity or sedentary behavior, and physical health.

Hemophagocytic lymphohistiocytosis and thrombotic microangiopathy after parvovirus B19 infection and renal transplantation: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disease characterized by hyperactivation of the immune system that causes hypercytokinemia and potentially multi organ failure. HLH can occur in patients with underlying rheumatic or autoinflammatory disorders. Additionally, HLH can develop in patients during infections or malignancies without a known genetic predisposition. CASE PRESENTATION: We herein report a patient, who presented with fever, both acute kidney and liver injury, anemia, thrombocytopenia and HSV stomatitis. HLH was diagnosed based on clinical criteria and qPCR revealed an acute parvovirus B19 infection as potential underlying infectious trigger. Treatment was started with both IVIG and dexamethasone. Subsequently, kidney biopsy demonstrated TMA. CONCLUSIONS: In rare cases both HLH and aHUS can occur simultaneously in a patient as a consequence of viral infections. Insights from this unusual case might help physicians understand this complex symptom constellation.

Predicting Success of a Digital Self-Help Intervention for Alcohol and Substance Use With Machine Learning.

BACKGROUND: Digital self-help interventions for reducing the use of alcohol tobacco and other drugs (ATOD) have generally shown positive but small effects in controlling substance use and improving the quality of life of participants. Nonetheless, low adherence rates remain a major drawback of these digital interventions, with mixed results in (prolonged) participation and outcome. To prevent non-adherence, we developed models to predict success in the early stages of an ATOD digital self-help intervention and explore the predictors associated with participant's goal achievement. METHODS: We included previous and current participants from a widely used, evidence-based ATOD intervention from the Netherlands (Jellinek Digital Self-help). Participants were considered successful if they completed all intervention modules and reached their substance use goals (i.e., stop/reduce). Early dropout was defined as finishing only the first module. During model development, participants were split per substance (alcohol, tobacco, cannabis) and features were computed based on the log data of the first 3 days of intervention participation. Machine learning models were trained, validated and tested using a nested k-fold cross-validation strategy. RESULTS: From the 32,398 participants enrolled in the study, 80% of participants did not complete the first module of the intervention and were excluded from further analysis. From the remaining participants, the percentage of success for each substance was 30% for alcohol, 22% for cannabis and 24% for tobacco. The area under the Receiver Operating Characteristic curve was the highest for the Random Forest model trained on data from the alcohol and tobacco programs (0.71 95%CI 0.69-0.73) and (0.71 95%CI 0.67-0.76), respectively, followed by cannabis (0.67 95%CI 0.59-0.75). Quitting substance use instead of moderation as an intervention goal, initial daily consumption, no substance use on the weekends as a target goal and intervention engagement were strong predictors of success. DISCUSSION: Using log data from the first 3 days of intervention use, machine learning models showed positive results in identifying successful participants. Our results suggest the models were especially able to identify participants at risk of early dropout. Multiple variables were found to have high predictive value, which can be used to further improve the intervention.