Epidemiological characteristics and outcome of viral respiratory tract infections in the first year after allogeneic hematopoietic cell transplantation.

Adverse outcomes of viral respiratory tract infections (RTI) have been reported in recipients of allogeneic hematopoietic cell transplantation. Using a laboratory-developed multiparameter PCR in a consecutive series of 242 patients, we found the highest incidence of viral RTI in the pre-engraftment phase. The occurrence of multiple episodes of viral RTI or viral pneumonia was significantly associated with a higher hazard of non-relapse mortality in the first year after transplantation. We observed a 90-day mortality of 19.7% after viral RTI, which was significantly different between patient groups stratified according to the ISI score.

In depth analysis of the HIV reservoir confirms effectiveness and safety of DTG/3TC in a phase 4 randomized controlled switch trial (RUMBA).

BACKGROUND: Reducing the number of active compounds for lifelong HIV treatment is of interest, especially to reduce potential long-term side effects. So far, available data assessing viral control, support the robustness and safety of 2DR (2-drug regimen) ART compared to 3DR. However, further in-depth investigations of the viral reservoirs are mandatory to guarantee long-term safety of these regimens regarding stable intact HIV-1 DNA copies, HIV-1 RNA transcripts and sustained immunological control. METHODS: The Rumba study is the first prospective randomized controlled trial evaluating the impact of switch from 3DR to 2DR on the viral reservoir. Participants on any stable 2nd generation INSTI-based 3DR regimen with HIV-1 RNA<50 copies/ml plasma for at least 3 months were randomized to switch to dolutegravir/lamivudine (DTG/3TC, N=89) or to switch or stay on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, N=45). After 48 weeks, virological, immunological and metabolic parameters were evaluated. RESULTS: We did not observe a significant difference in change over time in the mean number of intact HIV-1 DNA copies/million CD4+ T cells with DTG/3TC compared to B/F/TAF. There was no evidence in this study that switching to DTG/3TC increased the active reservoir by HIV-1 transcription. No significant changes in pro-inflammatory cytokines or major immune cell subsets were observed. Changes in exhaustion and activation of specific cellular subsets were small and bidirectional. Metabolic outcomes are similar between the treatment regimens. CONCLUSIONS: This study confirms the safety of DTG/3TC compared to B/F/TAF through viral control after in-depth investigations of the intact HIV-1 reservoir, HIV-1 transcription and inflammatory markers.

A Randomized Controlled Trial on the Timing of Soft-Tissue Augmentation in Immediate Implant Placement: Hard-Tissue Changes and Clinical Outcome.

AIM: To assess the impact of the timing of soft-tissue augmentation (STA) on mean buccal bone changes following immediate implant placement (IPP) in the anterior maxilla. MATERIALS AND METHODS: Patients with a failing tooth and intact buccal bone wall in the anterior maxilla (15-25) were enrolled in this randomized controlled trial. Following single IIP and socket grafting, they were randomly allocated to the control group (immediate STA performed during the same surgical procedure) or the test group (delayed STA performed 3 months later). Implants were placed with a surgical guide and immediately restored with an implant-supported provisional crown. Changes in bone dimensions were assessed using superimposed CBCT images taken prior to surgery and at 1-year follow-up. Clinical outcomes were registered at 1-year follow-up. RESULTS: Twenty patients were randomized to each group (control: 16 females, 4 males, mean age 57.6; test: 9 females, 11 males, mean age 54.2). Ten patients in the control group and 13 patients in the test group had a thick bone wall phenotype. Estimated marginal mean horizontal buccal bone loss at 1 mm below the implant shoulder was -0.553 and -0.898 mm for the control and test group, respectively. The estimated mean difference of 0.344 mm in favour of the control group was not significant (95% CI: -0.415 to 1.104; p = 0.363). Also at all other horizontal and vertical levels, no significant differences could be observed between the groups. The combination of socket grafting and STA enabled counteraction of any buccal soft-tissue loss (≥ 0 mm) at 1 mm below the implant shoulder in 82% of the patients in the control group and in 75% of the patients in the test group (p = 1.000). The clinical outcome was favourable in both groups, yet implants in the control group demonstrated slightly less marginal bone loss (median difference 0.20 mm; 95% CI: 0.00-0.44; p = 0.028). CONCLUSION: In patients with an intact and mainly thick buccal bone wall in the anterior maxilla, the timing of STA following IIP had no significant impact on mean buccal bone loss. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05537545.

A multi-centre randomized controlled trial comparing connective tissue graft with collagen matrix to increase soft tissue thickness at the buccal aspect of single implants: 3-Year results.

AIM: To compare connective tissue graft (CTG) with collagen matrix (CMX) in terms of increase in buccal soft tissue profile (BSP) when applied at single implant sites. MATERIALS AND METHODS: Patients with a single tooth gap in the anterior maxilla and horizontal mucosa defect were enrolled in a multi-centre randomized controlled trial. All were fully healed sites with a bucco-palatal bone dimension of at least 6 mm, and received an immediately restored single implant using a full digital workflow. Patients were randomly allocated to the control (CTG) or test group (CMX: Geistlich Fibro-Gide, Geistlich Pharma AG, Wolhusen, Switzerland) to increase buccal soft tissue thickness. Primary endpoints were increase in BSP at T1 (immediately postop), T2 (3 months), T3 (1 year) and T4 (3 years) based on superimposed digital surface models. Secondary endpoints included patient-reported, clinical and aesthetic outcomes. RESULTS: Thirty patients were included per group (control group: 15 males, 15 females, mean age 50.1 years; test group: 14 males, 16 females, mean age 48.2 years) and 50 could be re-examined at T4. The changes in BSP over time were significantly different between the groups (p < .001). At T4, the estimated mean increase in BSP amounted to 0.83 mm (95% confidence interval [CI]: 0.58-1.08) in the control group and 0.48 mm (95% CI: 0.22-0.73) in the test group. The estimated mean difference of 0.35 mm (95% CI: 0.06-0.65) in favour of the control group was significant (p = .021). No significant differences between the groups could be observed in terms of patients' aesthetic satisfaction (p = .563), probing depth (p = .286), plaque (p = .676), bleeding on probing (p = .732), midfacial recession (p = .667), Pink Esthetic Score (p = .366) and Mucosal Scarring Index (p = .438). However, CMX resulted in significantly more marginal bone loss (-0.43 mm; 95% CI: -0.77 to -0.09; p = .015) than CTG. CONCLUSIONS: CTG was more effective in increasing buccal soft tissue profile and resulted in less marginal bone loss than CMX. Therefore, CTG remains the gold standard to increase soft tissue thickness at implant sites. CLINICAL TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov (NCT04210596).

A multi-centre randomized controlled trial on alveolar ridge preservation with immediate or delayed implant placement: Need for soft-tissue augmentation.

AIM: To assess the impact of the timing of implant placement following alveolar ridge preservation (ARP) on the need for soft-tissue augmentation (STA) and to identify the risk factors for horizontal and vertical soft-tissue loss. MATERIALS AND METHODS: Patients with a single failing tooth in the anterior maxilla (15-25) were treated at six centres. Following tooth extraction, they were randomly allocated to the test group (immediate implant placement, IIP) or control group (delayed implant placement, DIP). ARP was performed in both groups and implants were immediately restored with an implant-supported provisional crown. Six months after tooth extraction and ARP, a panel of five blinded clinicians assessed the need for STA on the basis of anonymized clinical pictures and a digital surface model. Lack of buccal soft-tissue convexity and/or mid-facial recession qualified for STA. Pre-operative and 6-month digital surface models were superimposed to assess horizontal and vertical soft-tissue changes. RESULTS: Thirty patients were included per group (test: 20 females, 10 males, mean age 53.1; control: 15 females, 15 males, mean age 59.8). The panel deemed STA as necessary in 24.1% and 35.7% of the cases following IIP and DIP, respectively. The difference was not statistically significant (odds ratio [OR] = 1.77; 95% confidence interval [CI] [0.54-5.84]; p = .343). Loss of buccal soft-tissue profile was higher following DIP (estimated mean ratio = 1.66; 95% CI [1.10-2.52]; p = .018), as was mid-facial recession (mean difference [MD] = 0.47 mm; 95% CI [0.12-0.83]; p = .011). Besides DIP, regression analysis identified soft-tissue thickness (-0.57; 95% CI [-1.14 to -0.01]; p = .045) and buccal bone dehiscence (0.17; 95% CI [0.01-0.34]; p = .045) as additional risk factors for mid-facial recession. Surgeons found IIP significantly more difficult than DIP (visual analogue scale MD = -34.57; 95% CI [-48.79 to -20.36]; p < .001). CONCLUSIONS: This multi-centre randomized controlled trial failed to demonstrate a significant difference in the need for STA between IIP and DIP when judged by a panel of blinded clinicians. Based on objective soft-tissue changes, patients with thin buccal soft tissues, with a buccal bone dehiscence and treated with a delayed approach appeared particularly prone to soft-tissue loss.

The impact of multimorbidity patterns on health-related quality of life in the general population: results of the Belgian Health Interview Survey.

BACKGROUND: Chronic diseases and multimorbidity are a major cause of disease burden-for patients, caregivers, and society. Little is known however about potential interaction effects between specific disease combinations. Besides an additive effect, the presence of multiple conditions could also act synergistically or antagonistically regarding the impact on patients' health-related quality of life (HRQoL). The aim was to estimate the impact of coexisting chronic diseases on HRQoL of the adult general Belgian population. METHODS: The Belgian Health Interview Survey 2018 provided data on self-reported chronic conditions and HRQoL (EQ-5D-5L) for a nationally representative sample. Linear mixed models were used to analyze two-way and three-way interactions of disease combinations on HRQoL. RESULTS: Multimorbidity had a prevalence of 46.7% (≥ 2 conditions) and 29.7% (≥ 3 conditions). HRQoL decreased considerably with the presence of multiple chronic diseases. 14 out of 41 dyad combinations and 5 out of 13 triad combinations showed significant interactions, with a dominant presence of negative/synergistic effects. Positive/antagonistic effects were found in more subjective chronic diseases such as depression and chronic fatigue. Conditions appearing the most frequently in significant disease pair interactions were dorsopathies, respiratory diseases, and arthropathies. CONCLUSIONS: Diverse multimorbidity patterns, both dyads and triads, were synergistically or antagonistically associated with lower HRQoL. Tackling the burden of multimorbidity is needed, especially because most disease combinations affect each other synergistically, resulting in a greater reduction in HRQoL. Further knowledge about those multimorbidity patterns with a greater impact on HRQoL is needed to better understand disease burden beyond mortality and morbidity data.

Neonatal magnesium levels are safe after maternal MgSO4 administration: a comparison between unexposed preterm neonates and neonates exposed for fetal neuroprotection or maternal eclampsia prevention-a cohort study.

To objective of this study was to compare neonatal magnesemia in the first 15 days of neonatal life between three groups: a control group not exposed to MgSO4, a neuroprotection group, and an eclampsia prevention group, and to explore its associations with child outcomes. A retrospective single-centre cohort study was performed in a tertiary care setting. Infants admitted at the neonatal intensive care unit born between 24 and 32 weeks' gestation, regardless of etiology of preterm birth, were included. The mean outcome measure was neonatal magnesemia (mmol/L). Linear mixed regression of neonatal magnesemia on exposure group and day of life was done. Generalised estimating equation models of child outcomes on neonatal magnesemia according to exposure group and day of life were made. The analyses showed that in neonatal magnesemia is significantly higher in the preeclampsia group compared to the control and neuroprotection groups. On the day of birth, this is irrespective of maternal magnesemia (preeclampsia vs control groups), and the maternal total dose or duration of MgSO4 administration (preeclampsia vs neuroprotection group). No differences were found in short-term composite outcome between the three groups. CONCLUSION: We found mean differences in neonatal magnesemia between children not exposed to MgSO4 antenatally, children exposed for fetal neuroprotection, and children exposed for maternal eclampsia prevention. A 4-g loading and 1-g/h maintenance doses, for fetal neuroprotection and eclampsia prevention, appear to be safe on the short term for the neonate. WHAT IS KNOWN: • Magnesium sulphate is a valuable medicine in obstetrics. The main indications are prevention of eclampsia and fetal neuroprotection. The most used dosage is a 4- or 6-g loading dose and a 1- or 2-g per h maintenance dose. It reduces neuromotor disabilities in extreme-to-moderate preterm born children. WHAT IS NEW: • Maternal concentrations are supraphysiological and the maternal total dose can be high. Concentrations in neonates appear to remain in safe ranges. A dosage of 4-g loading and 1 g/h seems safe for the preterm neonate on the short term.

Effects of a theory-based advance care planning intervention for nursing homes: A cluster randomized controlled trial.

BACKGROUND: Uptake of advance care planning in routine nursing home care is low. Through extensive literature review, theoretical development, and stakeholder involvement, we developed the ACP+ intervention. AIMS: To evaluate the effects of ACP+ on the knowledge and self-efficacy (confidence in own skills) of nursing home care staff concerning advance care planning. DESIGN: Cluster randomized controlled trial, conducted between February 2018 and January 2019 (NCT03521206, clinicaltrials.gov). ACP+ is a multicomponent intervention aimed at training and supporting nursing home staff and management in implementing advance care planning in nursing home practice through a train-the-trainer approach over 8 months. Fourteen nursing homes were randomized using a matched-pairing strategy, seven received ACP+, seven followed usual practice. Analyses (intention-to-treat) involved linear mixed models. SETTING/PARTICIPANTS: Nursing homes in Flanders (Belgium). RESULTS: 694 of 1017 care staff (68% response rate) at baseline and 491 of 989 care staff (50%) post-intervention (8 months) returned questionnaires. Post-intervention, care staff's self-efficacy concerning advance care planning was significantly higher in the intervention than in the control group (baseline-adjusted mean difference 0.57; 95% CI 0.20-0.94; p = 0.003; Cohen's d = 0.30). Advance care planning knowledge (95% CI 0.95-1.15; p = 0.339; ratio: 1.04) did not differ significantly between groups. CONCLUSIONS: The ACP+ intervention for nursing homes improved care staff's self-efficacy but not their knowledge concerning advance care planning. Considering the comprehensive and multi-component approach used, these effects were smaller than expected. Reasons for this may be related to the chosen follow-up period, outcomes and measurements, or to the intervention itself and its implementation.

Normal subchondral high T2 signal on MRI mimicking sacroiliitis in children: frequency, age distribution, and relationship to skeletal maturity.

OBJECTIVES: To determine patterns of variation of subchondral T2 signal changes in pediatric sacroiliac joints (SIJ) by location, age, sex, and sacral apophyseal closure. METHODS: MRI of 502 SIJ in 251 children (132 girls), mean age 12.4 years (range 6.1-18.0), was obtained with parental informed consent. One hundred twenty-seven out of 251 had asymptomatic joints and were imaged for non-rheumatologic reasons, and 124 had low back pain but no sign of sacroiliitis on initial clinical MRI review. After calibration, three subspecialist radiologists independently scored subchondral signal changes on fat-suppressed fluid-sensitive sequences from 0 to 3 in 4 locations, and graded the degree of closure of sacral segmental apophyses. Associations between patient age, sex, signal changes, and apophyseal closure were analyzed. RESULTS: Rim-like subchondral increased T2 signal or "flaring" was much more common at sacral than iliac SIJ margins (72% vs 16%, p < 0.001) and was symmetrical in > 90% of children. Iliac flaring scores were always lower than sacral, except for 1 child. Signal changes decreased as sacral apophyses closed, and were seen in < 20% of subjects with fully closed apophyses. Signal changes were more frequent in boys, and peaked in intensity later than for girls (ages 8-12 vs. 7-10). Subchondral signal in iliac crests was high throughout childhood and did not correlate with other locations. CONCLUSIONS: Subchondral T2 "flaring" is common at SIJ of prepubertal children and is generally sacral-predominant and symmetrical. Flaring that is asymmetrical, greater in ilium than sacrum, or intense in a teenager with closed apophyses, is unusual for normal children and raises concern for pathologic bone marrow edema. KEY POINTS: • A rim of subchondral high T2 signal is commonly observed on MRI at pediatric sacroiliac joints, primarily on the sacral side before segmental apophyseal closure, and should not be confused with pathology. • Unlike subchondral signal changes elsewhere, high T2 signal underlying the iliac crest apophyses is a near-universal normal finding in children that usually persists throughout adolescence. • The following patterns are unusual in normal children and are suspicious for pathology: definite iliac flaring, iliac flaring more intense than sacral flaring, left-right difference in flaring, definite flaring of any pattern in teenagers after sacral apophyseal closure.

Magnetic resonance imaging findings in the normal pediatric sacroiliac joint space that can simulate disease.

BACKGROUND: Magnetic resonance imaging (MRI) features of active sacroiliac joint inflammation include joint space fluid and enhancement, but it is unclear to what extent these are present in normal children. OBJECTIVE: To describe normal MRI appearances of pediatric sacroiliac joint spaces in boys and girls of varying ages. MATERIALS AND METHODS: In this ethics-approved prospective study, 251 children (119 boys, 132 girls; mean age: 12.4 years, range: 6.1-18.0 years), had both oblique-coronal T1-weighted and short tau inversion recovery (STIR) sacroiliac joint MRI. Of these, 127 were imaged for other reasons and had asymptomatic sacroiliac joints ("normal cohort") while 124 had low back pain with no features of sacroiliitis on initial clinical MRI review ("low-back-pain cohort"). Post-gadolinium T1-weighted sequences were available in 16/127 normal and 124/124 low-back-pain subjects. Three experienced radiologists scored high signal in the sacroiliac joint space on STIR (score 0=absent; 1=high signal compared to normal bone marrow present anywhere in the joint but not as bright as fluid [compared to vessels, cerebrospinal fluid]; 2=definite fluid signal in part of the joint; 3=definite fluid signal, entire vertical height, majority of slices) and, when available, joint space post-contrast enhancement (0=no high signal/enhancement; 1=thin, symmetrical, mildly increased linear high signal present in the joint space; 2=focal, thick or intense enhancement). Associations between joint signal scores, age, gender and sacral apophyseal closure were analysed. RESULTS: Increased signal on STIR (score 1-3) was present in 74.7% of pediatric sacroiliac joint spaces, as intense as fluid in 18.4%. There was no significant difference in proportion by gender, side or cohort, but girls showed peak signal earlier than boys (10 years old vs. 12 years old, respectively). On post-gadolinium T1-weighted sequences, a thin rim of increased signal was nearly universally seen in sacroiliac joint spaces without focal, intense or thick post-contrast enhancement. CONCLUSION: Sacroiliac joint spaces of most children demonstrate mildly increased signal on STIR, compared to normal bone marrow, and thin rim-like enhancement on post-contrast T1 images, likely related to cartilage. These findings should not be confused with sacroiliitis.

Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis.

Importance: Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm. Objective: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes. Data Sources: Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts. Study Selection: Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria. Data Extraction and Synthesis: In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality. Main Outcomes and Measures: The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days. Results: A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P < .001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P = .52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16). Conclusions and Relevance: In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality. Trial Registration: PROSPERO Identifier: CRD42021230155.

Mycoplasma genitalium acquisition and macrolide resistance after initiation of HIV pre-exposure prophylaxis in men who have sex with men.

OBJECTIVES: Recent evidence shows that patients using HIV pre-exposure prophylaxis (PrEP) have an increased rate of bacterial STIs, including syphilis, chlamydia and gonorrhoea. Our study aimed to describe the acquisition and the susceptibility for macrolides of Mycoplasma genitalium in men who have sex with men (MSM) on PrEP. METHODS: We studied all MSM who started PrEP in the AZ Sint-Jan Hospital Bruges from 1 June 2017 to 31 March 2019 with at least one follow-up visit. Patients were screened for M. genitalium and other STIs with pooled rectal swabs, pharyngeal swabs and first-voided urine, and blood samples at baseline and quarterly intervals after initiating PrEP. TaqMan Array Card technology was used to detect M. genitalium and determine macrolide-resistance mediating mutations in region V of the 23S rRNA gene (A2058G, A2059G, A2058C and others). Patients with an STI were treated based on a national guideline. RESULTS: 131 MSM (median age 40 years, range 20-79) were included in the study. The median follow-up time was 12 months (IQR 6.1-17). Baseline prevalence of M. genitalium was 6.9% and incidence rate after PrEP initiation was 28.8 per 100 person-years (95% CI 21.7 to 37.2), without significant differences in proportions between the first four quarterly intervals. All but one acquisitions were asymptomatic. Younger age and positivity for M. genitalium at baseline were significantly associated with incident M. genitalium acquisition. The observed proportion of macrolide resistance increased not significantly from 44% at baseline to 57%-86% after PrEP initiation. None of the 27 macrolide-resistant M. genitalium acquisitions could be linked to azithromycin exposure in the three preceding months. CONCLUSIONS: After initiation of PrEP, we found a stable incidence of almost exclusively asymptomatic M. genitalium. However, a non-significant trend of an increased percentage of macrolide-resistant strains was observed.

Validation of the FNIH sarcopenia criteria and SOF frailty index as predictors of long-term mortality in ambulatory older men.

OBJECTIVE: we aimed to evaluate the Foundation for the National Institutes of Health (FNIH) criteria for weakness and low muscle mass and the Study of Osteoporotic Fractures (SOF) frailty index for prediction of long-term, all-cause mortality. DESIGN: community-based cohort study. SETTING: semi-rural community of Merelbeke (Belgium). SUBJECTS: ambulatory men aged 74 and more (n = 191). METHODS: weakness was defined on previously established criteria as low grip strength (<26 kg) or low grip strength-to-body mass index (BMI) ratio (<1.00). Low muscle mass (dual-energy x-ray absorptiometry) was categorised as low appendicular lean mass (ALM; predefined <19.75 kg) or low ALM-to-BMI ratio (predefined <0.789). Frailty status was assessed using the components of weight loss, inability to rise from a chair and poor energy (SOF index). Survival time was calculated as the number of months from assessment in 2000 until death or up to 15 years of follow-up. RESULTS: mean age of the participants was 78.4 ± 3.5 years. Combined weakness and low muscle mass was present in 3-8% of men, depending on the criteria applied. Pre-frailty and frailty were present in 30 and 7% of men, respectively. After 15 years of follow-up, 165 men (86%) died. Both the presence of combined weakness and low ALM-to-BMI ratio (age-adjusted HR = 2.50, 95% CI = 1.30-4.79) and the presence of SOF frailty (age-adjusted HR = 2.64, 95% CI = 1.44-4.86) were associated with mortality. CONCLUSIONS: our findings confirm the predictive value for mortality of the non-distribution-based FNIH criteria and SOF index in older community-dwelling Belgian men.

Assessment of Within- and Inter-Patient Variability of Uremic Toxin Concentrations in Children with CKD.

To promote improved trial design in upcoming randomized clinical trials in childhood chronic kidney disease (CKD), insight in the within- and inter-patient variability of uremic toxins with its nutritional, treatment- and patient-related confounding factors is of utmost importance. In this study, the within- and inter-patient variability of a selection of uremic toxins in a longitudinal cohort of children diagnosed with CKD was assessed, using the intraclass correlation coefficient (ICC) and the within-patient coefficient of variation (CV). Subsequently, the contribution of anthropometry, estimated glomerular filtration rate (eGFR), dietary fiber and protein, and use of (prophylactic) antibiotics to uremic toxin variability was evaluated. Based on 403 observations from 62 children (median seven visits per patient; 9.4 ± 5.3 years; 68% males; eGFR 38.5 [23.1; 64.0] mL/min/1.73 m2) collected over a maximum of 2 years, we found that the within-patient variability is high for especially protein-bound uremic toxins (PBUTs) (ICC < 0.7; within-patient CV 37-67%). Moreover, eGFR was identified as a predominant contributor to the within- and inter-patient variability for the majority of solutes, while the impact of the child's anthropometry, fiber and protein intake, and antibiotics on the variability of uremic toxin concentrations was limited. Based on these findings, we would recommend future intervention studies that attempt to decrease uremic toxin levels to select a (non-dialysis) CKD study population with a narrow eGFR range. As the expected effect of the selected intervention should exceed the inter-patient variability of the selected uremic toxins, a narrow eGFR range might aid in improving the trial design.

Indoxyl Sulfate Contributes to Impaired Height Velocity in (Pre)School Children.

Introduction: Growth failure is considered the most important clinical outcome parameter in childhood chronic kidney disease (CKD). Central to the pathophysiology of growth failure is the presence of a chronic proinflammatory state, presumed to be partly driven by the accumulation of uremic toxins. In this study, we assessed the association between uremic toxin concentrations and height velocity in a longitudinal multicentric prospective pediatric CKD cohort of (pre)school-aged children and children during pubertal stages. Methods: In a prospective, multicentric observational study, a selection of uremic toxin levels of children (aged 0-18 years) with CKD stage 1 to 5D was assessed every 3 months (maximum 2 years) along with clinical growth parameters. Linear mixed models with a random slope for age and a random intercept for child were fitted for height (in cm and SD scores [SDS]). A piecewise linear association between age and height was assumed. Results: Data analysis included data from 560 visits of 81 children (median age 9.4 years; 2/3 male). In (pre)school aged children (aged 2-12 years), a 10% increase in concurrent indoxyl sulfate (IxS, total) concentration resulted in an estimated mean height velocity decrease of 0.002 SDS/yr (P < 0.05), given that CKD stage, growth hormone (GH), bicarbonate concentration, and dietary protein intake were held constant. No significant association with height velocity was found in children during pubertal stages (aged >12 years). Conclusion: The present study demonstrated that, especially IxS contributes to a lower height velocity in (pre)school children, whereas we could not find a role for uremic toxins with height velocity during pubertal stages.

Physical function measurements predict mortality in ambulatory older men.

BACKGROUND: To assess and compare the predictive value of physical function measurements (PFMs) for all-cause mortality in older men and to evaluate the Timed Up and Go test (TUG) as a predictor in subjects with underlying comorbidity. DESIGN: Observational study of a population-based sample of 352 ambulatory older men aged 71-86 at study baseline. The Rapid disability rating scale-2, 36-Item short form health survey, Grip strength, Five times sit-to-stand test, Standing balance, and TUG were determined at baseline. Associations with all-cause mortality were assessed using Cox proportional hazard analyses. Age, Body mass index (BMI), smoking status, education, physical activity and cognitive status were included as confounders. Follow-up exceeded 15 years. Comorbidity status was categorized into cardiovascular disease, chronic obstructive pulmonary disease (COPD) and diabetes mellitus. RESULTS: All examined PFMs were associated with all-cause mortality. TUG was the best predictor (adjusted HR per SD increase = 1·58, 95% CI = 1·40-1·79, P < 0·001) for global mortality and continued to be predictive in subjects with cardiovascular disease (adjusted HR per SD increase = 1·80, 95% CI = 1·40-2·33, P < 0·001). CONCLUSIONS: The assessment of physical functioning is important in the evaluation of older persons. We encourage the use of the TUG as a reliable, quick and feasible screening tool in clinical settings.

Factors Related to Police Reporting in Sexual Assault Care Centers: Are We Underestimating the Role of Support Persons?

Few victims of sexual assault (SA) report to the police. Research on the role of support persons in victims' reporting is sparse. We address this gap by examining the association of victim, assailant, victimization incident, and support characteristics with reporting rates among victims attending sexual assault care centers (SACCs). Logistic regression results show that type of SA, delay between SA and presentation at SACC, and presence of an informal support person at SACC and SACC site are significantly associated with police reporting. These findings reveal the importance of targeting victims' support persons to alter reporting behavior among SA victims.

In Vitro Investigation into the Effect of Cryopreservation on the Mechanical Characteristics of Dental Hard Tissues.

Previous research has reported on hidden damage within the dentin introduced by cryopreservation, but the effect on the mechanical properties of the hard tissues at tooth level remains unclear. The main objective of this study is to investigate the effect of cryopreservation on the mechanical properties of teeth. A matched sample of 234 premolars of 117 children (9 ≤ age ≤ 16 years), bilaterally extracted for orthodontic reasons, were included. For each child, one tooth was randomly allocated to the cryopreservation group and the contralateral tooth was assigned to the control group. Static compression tests were performed to determine load to failure, stiffness, and toughness. In a subgroup of 20 teeth, a cyclic preloading or chewing simulation was performed. Additionally, the fracture mode was determined, and the microstructure of the fractured surfaces was examined using a scanning electron microscope (SEM). Linear mixed model analyses could not detect a statistical difference in the mean load to failure (p = 0.549), mean toughness (p = 0.968), or mean stiffness (p = 0.150) between cryopreserved and non-cryopreserved teeth. No significant difference in load to failure after cyclic preloading was detected between groups (p = 0.734). SEM analysis revealed comparable fracture characteristics between groups. It is concluded that cryopreservation does not affect the mean load to failure, stiffness, or toughness of teeth, indicating that hidden damage in the dentin is not critical at tooth level.

Infectious diarrhea after allogeneic hematopoietic cell transplantation assessed by a multiplex polymerase chain reaction assay.

OBJECTIVES: To determine the incidence of infectious diarrhea after allogeneic hematopoietic cell transplantation (HCT) using a multiplex polymerase chain reaction assay and assess risk factors for developing infectious diarrhea. METHODS: This was a single-center retrospective study of 140 consecutive allogeneic HCT recipients. Infectious diarrhea was assessed using a laboratory-developed multiplex polymerase chain reaction the first year after transplantation. RESULTS: The incidence rate of infectious diarrhea episodes was 47 per 100 person-years, with the highest rate observed in the pre-engraftment phase. Most episodes were seen as nosocomial infections (38%) and most affected patients (82%) had only one episode of infectious diarrhea. The cumulative incidence of at least one episode of infectious diarrhea was 32% after 1 year. Nonrelapse mortality was higher in transplant recipients with at least one episode of infectious diarrhea (hazard ratio (HR) 2.02, 95% CI = 1.07-3.80). The most frequently observed pathogens were Clostridium difficile, adenovirus, Enteropathogenic Escherichia coli, and Campylobacter jejuni. Patients with acute lower gastrointestinal graft-vs-host disease stage 3 or 4 (HR 3.68, 95% CI = 1.57-8.63) conferred a higher risk for a first infectious diarrhea episode. CONCLUSION: Infectious diarrhea after allogeneic HCT was seen in about one-third of the patients, mostly as nosocomial infection in the pre-engraftment phase.