Study Time Points Research Articles

Structural Changes in the Elements of the Blood-Brain Barrier of the Hippocampus in Rats after Exposure to Perinatal Hypoxia and the Potential for Their Pharmacological Correction

Objectives. To study the dynamics of structural changes in elements of the blood-brain barrier of the hippocampus during the early postnatal period and subsequent ontogeny after exposure to perinatal hypoxia and to investigate the potential for pharmacological correction of these changes. Materials and methods. Experiments were performed on Wistar laboratory rats with a model of the encephalopathy of premature human infants using electron microscopy. Results. Perinatal hypoxia was followed by detection of structural damage to capillary walls: there were increases in the size of endotheliocytes, increases in the numbers of cytoplasmic processes, changes in the diameter of capillary lumens, and delays in the formation of the basal membrane. A marked endothelium-protecting effect was seen with the formulation Salifen at all study time points. Salifen was found to decrease the intensity of the reactions of elements of the blood-brain barrier to the harmful actions of perinatal hypoxia. Conclusions. Perinatal hypoxia has marked damaging effects on all elements of the blood-brain barrier of the hippocampus, the induced lesions being detected at both the early stages of postnatal development and in animals reaching adulthood. Use of Salifen immediately after exposure to perinatal hypoxia eliminated much of the structural damage to endotheliocytes and the basal membrane by the juvenile period. This study provides grounds for believing that the use of Salifen in ischemic brain injury in neonates has potential and our series of further preclinical studies will be continued.

Changes in Muscle Morphology Following Gastrocnemius Recession for Achilles Tendinopathy: A Prospective Cohort Imaging Study.

Background. The purpose of this study was to evaluate changes in posterior compartment muscle volume and intramuscular fat content following gastrocnemius recession in people with Achilles tendinopathy (AT). Methods. Eight patients diagnosed with unilateral recalcitrant AT and an isolated gastrocnemius contracture participated in this prospective cohort study. Magnetic resonance imaging was performed on both limbs of each participant before and 6 months following an isolated gastrocnemius recession. Involved limb muscle volumes and fat fractions (FFs) of the medial gastrocnemius, lateral gastrocnemius, and soleus muscle were normalized to the uninvolved limb. Preoperative to postoperative comparisons were made with Wilcoxon signed-rank tests. Results. Soleus or lateral gastrocnemius muscle volumes or FFs were not significantly different between study time points. A significant difference was found in medial gastrocnemius muscle volume (decrease; P = .012) and FF (increase; P = .017). Conclusion. A major goal of the Strayer gastrocnemius recession, selective lengthening of the posterior compartment while preserving soleus muscle morphology, was supported. The observed changes isolated to the medial gastrocnemius muscle may reduce ankle plantarflexion torque capacity. Study findings may help inform selection of surgical candidates, refine anticipated outcomes, and better direct postoperative rehabilitation following gastrocnemius recession for AT.Levels of Evidence: Level IV: Prospective cohort study.

Efficacy of Cognition Support Formula\xae on cognitive function in older adults with subjective cognitive impairment: a protocol for a 26-week, randomised, double-blind, placebo-controlled trial

BackgroundDue to an ageing population in Australia there has been an increase in the number of older adults with subjective cognitive impairment (SCI), a self-reported decline in cognitive function associated with an increased risk of mild cognitive impairment and dementia. There is no current, recommended treatment for SCI; therefore, the effectiveness of a supplement approved by the Therapeutic Goods Association that has the potential to enhance cognitive function in an at-risk cohort should be tested. The primary aim of this proposed research is to determine the efficacy of 6 months of treatment with BioCeuticals Cognition Support Formula® (containing Bacopa monniera (brahmi), Ginkgo biloba, Panax ginseng and alpha-lipoic acid) on cognition in older adults with SCI (utilising the CogState® one card learning and identification tests as co-primary outcome measures of visual short-term memory and attention; mean speed (ms), accuracy (%), and total number of hits, misses, and anticipations) compared with placebo. The secondary aims are to assess an improvement in other cognitive domains (executive functioning, processing speed, and working memory), evaluate safety, adverse effects, and determine efficacy on mood, fatigue, and neurocognition. It is expected that improvements across the study timepoints in the co-primary outcomes in the active treatment group (compared with placebo) will be evident.MethodOne-hundred and twenty participants will be recruited for the randomised, double-blind, placebo-controlled study. Participants will be randomly assigned to one of the treatment groups (active or placebo) at a 1:1 ratio, and will be required to complete a series of cognitive (using CogState®), mood (using the Depression, Anxiety, Stress Scale (DASS-42) and Short Health Anxiety Inventory (SHAI)), and fatigue (using the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F)) tasks at baseline (0 months), the midpoint (3 months), and the endpoint (6 months). These tasks will be evaluated between timepoints (baseline vs. midpoint, midpoint vs. endpoint, and baseline vs. endpoint). Neurocognition will be measured by electroencephalography at baseline and at the endpoint in half of the participants. Adverse effects will be documented over the 6-month trial period.DiscussionThis is the first study to test the efficacy of Cognition Support Formula® on cognition in older adults with SCI. As people with SCI have an increased risk of dementia, and there are limited treatments options for this population, it is important to assess a supplement that has the potential to enhance cognitive function.Trial registrationUniversal Trial Number (UTN), U1111–1196-9548. Australian New Zealand Clinical Trials Registry, ACTRN12617000945325. Registered on 30 June 2017.

Metabolites of phosphate flame retardants and alternative plasticizers in urine from intensive care patients

Several regulatory offices called for the phase-out of di (2-ethylhexyl) phthalate (DEHP) in medical devices if safer alternatives are available. In medical devices, the occurrence of alternative plasticizers (APs) is widely variable among types of devices. However, plasticizer use is constantly evolving, as there is no reference to guide manufacturers in the choice and amount to be integrated into their products. As intensive care unit (ICU) patients need numerous indwelling plastic devices during their treatment, we hypothesized that these patients are exposed to APs and phosphate flame retardants and plasticizers (PFRs). Urinary metabolites of APs and PFRs were analyzed in the urine of adult ICU patients (n = 24) over a time period of four days. Our results show that adult ICU patients are exposed to PFRs as well as to APs concentrations were much lower compared to the levels of DEHP metabolites in the same samples. However, significantly higher than in controls (n = 15) this exposure resulted in detectable urinary levels in almost every patient and at every studied time point. Increasing temporal trends were observed for several metabolites from admission until day 3 at ICU. The use of specific medical devices, such as continuous venovenous hemofiltration (CVVH) and extracorporeal membrane oxygenation (ECMO), was associated with an increase in urinary concentrations for several PFR metabolites, despite the lack of information on the presence of these plasticizer chemicals in such medical devices. Further research into the possibly toxic effects of these chemicals released from medical devices is urgently needed.

A pilot randomized trial of five financial incentive strategies to increase study enrollment and retention rates

BackgroundEnrollment and retention difficulties remain major barriers to conducting clinical trials. Financial incentives may promote clinical trial enrollment, however delivery methods to maximize enrollment, maximize retention, and minimize cost remains uncertain. MethodsWe conducted a single-blind, web-based randomized controlled trial of five financial incentive strategies on enrollment and retention rates in a longitudinal study of advance directives among community-dwelling older adults. Participants were eligible to receive a fixed total financial incentive, but the disbursement amounts at each study timepoint (baseline, 2-weeks, 4-weeks, and 6-weeks) differed between study arms. At each timepoint, participants completed a different advance directive. We conducted an intention-to-treat analysis for the primary and secondary outcomes of enrollment and retention. Results1803 adults were randomized to one of five incentive strategies: constant n = 361; increasing n = 357; U-shaped n = 361; surprise n = 360; self-select n = 364. Overall, 989 (54.9%) participants elected to enroll in the advance directive study. There were no differences in enrollment rates between the control (constant 53.5%) and any of the four intervention study arms (increasing 54.3%, p = 0.81; U-shaped 57.3%, p = 0.30; surprise 56.9%, p = 0.35; and self-select 52.2%, p = 0.73). There were no differences in retention rates between the control (constant 2.1%) and any of the four intervention study arms (increasing 5.2%, p = 0.09; U-shaped 3.9%, p = 0.23; surprise 2.4%, p = 0.54; self-select 2.1%, p = 0.63). ConclusionsFinancial incentive programs for trial enrollment informed by behavioral economic insights were no more effective than a constant-payment approach in this web-based pilot study.

Stool pH and Short/Branched Chain Fatty Acids in Infants Receiving Extensively Hydrolyzed Formula, Amino Acid Formula, or Human Milk Through Two Months of Age (P11-076-19)

ObjectivesInfant feeding influences early development of the gut microbiome, colonization pattern, and community structure. Metabolites, including short- and branched-chain fatty acids (S/BCFA) (e.g., butyrate, propionate), produced by colonic bacteria serve as signaling molecules, influence immunity, and reduce luminal pH in the gastrointestinal environment. The objective of this study was to evaluate stool S/BCFA and pH in infants fed with different sources of dietary protein. MethodsIn this multicenter, double-blind, controlled, parallel-group, pilot study, healthy term infants were randomized to receive one of two infant formulas (IF): amino-acid based (AAF; n = 25) or extensively hydrolyzed cow’s milk protein (EHF; n = 28) from Baseline (1-7 days of age) up to 60 days of age. A human milk reference group (HM; n = 25) received mother’s own milk over the same period. Diethyl ether extractions of S/BCFA from stool samples (Baseline, Day 30, and Day 60) were quantified by gas chromatography (Clarus 580; PerkinElmer) using a fused silica capillary column (Nukol 30m × 0.25mm id × 0.25μm film). Mean stool S/BCFA (μmol/g) and pH were analyzed by repeated measures analysis of variance (ANOVA). ResultsComplete stool data (all study time points) were available for 49 participants. Stool pH (∼6) was similar among groups at Baseline with no significant changes for HM and EHF groups through Day 60. The AAF group was significantly higher at Days 30 and 60 (Figure 1). Total SCFA were similar for all groups through Day 60. Butyrate increased significantly from Baseline to Day 60 in the EHF group (P = 0.026) and was significantly higher vs HM at Days 30 and 60 (P = 0.0009 and 0.0004 respectively). Butyrate was significantly higher for AAF vs HM at Day 60 only (P = 0.038). Propionate was significantly higher for EHF and AAF at Day 30 (P = 0.0009 and < 0.0001 respectively) and AAF only at Day 60 (P = 0.005) vs HM. Total and individual BCFA increased for AAF and EHF groups vs HM through Day 60. ConclusionsDistinct patterns of pH and microbial metabolites were demonstrated for infants receiving mother’s own milk compared to amino acid-based or extensively hydrolyzed protein formula. Providing different sources of dietary protein early in life may influence gut microbiota and metabolites. Funding SourcesMead Johnson Pediatric Nutrition Institute. Supporting Tables, Images and/or Graphs▪

Stool Microbiota in Infants Receiving Extensively Hydrolyzed Formula, Amino Acid Formula, or Human Milk Through Two Months of Age (FS04-07-19)

ObjectivesInfant feeding practices play a central role in development of gut microbiome and community structure. Our goal was to test the hypothesis that diets with intact or extensively hydrolyzed proteins or free amino acids may differentially affect the intestinal microbiota composition and immune reactivity. MethodsThis multicenter, double-blind, controlled, parallel-group, pilot study compared stool microbiota outcomes from Baseline (1-7 days of age) up to 60 days of age in healthy term infants. Infants received mother’s own milk (assigned to human milk [HM] reference group) (n = 25) or were randomized to receive one of two infant formulas: amino-acid based (AAF; n = 25) or extensively hydrolyzed cow’s milk protein (EHF; n = 28). Neither study formula included added Lactobacillus rhamnosus GG. DNA was extracted (Baseline, Day 30, Day 60), 16S rRNA genes were amplified and sequenced (Illumina MiSeq), and exact amplicon sequence variants (ASV) were assigned using the DADA2 model. Alpha (Shannon, Simpson, Chao1) and beta diversity (Bray Curtis distance) and differential abundance in taxa were analyzed. Relative ASV enrichment (Baseline vs Day 60) was visualized using heat maps and taxa abundance was analyzed by DESEq2 in R (ver 3.4.3). ResultsComplete stool data (all study time points) were available for 49 participants. Baseline alpha diversity measures were similar among groups. The HM group remained stable throughout the study. However, alpha diversity measures by Day 60 were significantly higher for AAF and EHF groups compared to HM. Significant group differences in beta diversity at Day 60 were detected (P < 0.001); AAF and EHF clustered more closely compared to the HM group. Relative Bifidobacterium abundance increased over time and was significantly enriched at Day 60 in the HM group (Figure, A). At Day 60, a significant increase in members of Firmicutes was detected for AAF and EHF groups; a decrease in Enterobacteriaceae (Escherichia) was observed for EHF (Figure, B). ConclusionsDistinct patterns of early neonatal microbiome establishment were demonstrated for infants receiving mother’s own milk compared to amino acid-based or extensively hydrolyzed protein infant formulas. Providing different sources of dietary protein early in life may impact gut microbiome development. Funding SourcesMead Johnson Pediatric Nutrition Institute. Supporting Tables, Images and/or Graphs▪▪

Greater Weight Gain in Treatment-naive Persons Starting Dolutegravir-based Antiretroviral Therapy.

Recent studies have reported weight gain in virologically suppressed persons living with human immunodeficiency virus (PLWH) switched from older antiretroviral therapy (ART) to newer integrase strand transfer inhibitor (INSTI)-based regimens. In this study, we investigated whether weight gain differs among treatment-naive PLWH starting INSTI-based regimens compared to other ART regimens. Adult, treatment-naive PLWH in the Vanderbilt Comprehensive Care Clinic cohort initiating INSTI-, protease inhibitor (PI)-, and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART between January 2007 and June 2016 were included. We used multivariable linear mixed-effects models to generate marginal predictions of weights over time, adjusting for baseline clinical and demographic characteristics. We used restricted cubic splines to relax linearity assumptions and bootstrapping to generate 95% confidence intervals. Among 1152 ART-naive PLWH, 351 initiated INSTI-based regimens (135 dolutegravir, 153 elvitegravir, and 63 raltegravir), 86% were male, and 49% were white. At ART initiation, median age was 35 years, body mass index was 25.1 kg/m2, and CD4+ T-cell count was 318 cells/μL. Virologic suppression at 18 months was similar between different ART classes. At all examined study time points, weight gain was highest among PLWH starting dolutegravir. At 18 months, PLWH on dolutegravir gained 6.0 kg, compared to 2.6 kg for NNRTIs (P < .05), and 0.5 kg for elvitegravir (P < .05). PLWH starting dolutegravir also gained more weight at 18 months compared to raltegravir (3.4 kg) and PIs (4.1 kg), though these differences were not statistically significant. Treatment-naive PLWH starting dolutegravir-based regimens gained significantly more weight at 18 months than those starting NNRTI-based and elvitegravir-based regimens.

CNS penetration of the CDK4/6 inhibitor ribociclib in non-tumor bearing mice and mice bearing pediatric brain tumors.

Ribociclib, an orally bioavailable small-molecule CDK4/6 inhibitor is currently undergoing evaluation to treat pediatric central nervous system (CNS) tumors. However, it is crucial that it penetrates the brain and tumor. Thus, the objectives of the present study were to derive a clinically relevant mouse dosage for cerebral microdialysis studies, and to characterize ribociclib CNS penetration in non-tumor bearing mice and in mice bearing DIPGx7 (glioma) cortical allograft tumors. A plasma pharmacokinetic study of ribociclib (100mg/kg, orally) was performed in CD1 nude mice bearing glioma cortical allografts to obtain initial plasma pharmacokinetic parameters and to derive D-optimal plasma sampling time-points for microdialysis studies. Using a cerebral microdialysis technique, the extracellular fluid (ECF) disposition of ribociclib was evaluated after a single oral ribociclib dose (100mg/kg) in non-tumor bearing mice and in mice bearing glioma cortical allografts. A one-compartment plasma model with absorption and ECF compartments were fit to plasma and ECF concentration-time data using a nonlinear mixed effects modeling approach (NONMEM 7.2). The mean unbound ribociclib plasma exposure (6812ng/ml*h) was similar to that observed clinically at recommended dosages in adults. The median ribociclib ECF to plasma partition coefficient (Kp,uu) in non-tumor bearing and glioma mice was 0.10 and 0.07, respectively, and was not statistically different (t test, p = 0.19). The CNS penetration observed was encouraging enough to move ribociclib forward with preclinical efficacy studies in models of pediatric brain tumors.

Bone Formation and Adaptive Morphology of the Anterior Tibial Muscle in 3-mm Daily Lengthening Using High-Fractional Automated Distraction and Osteosynthesis with the Ilizarov Apparatus Combined with Intramedullary Hydroxyapatite-Coated Wire.

Purpose We studied osteogenesis and morphofunctional features of the anterior tibial muscle using 3-mm high-frequency automated lengthening with the Ilizarov apparatus alone and in combination with intramedullary nailing. Material and Methods Tibia was lengthened with a round-the-clock automated distractor at a 3-mm daily rate for 10 days in 16 mongrel dogs. In group 1 (n = 8), a 1.8-mm intramedullary titanium wire coated with hydroxyapatite was introduced into the tibial canal followed by Ilizarov frame mounting and transverse osteotomy of the diaphysis. Distraction mode was 0.025 mm x 120 increments a day. In group 2 (n = 8), distraction mode was the same but nailing was not used. Bone formation and the anterior tibial muscle were studied at two time points: (1) upon distraction completion; (2) three months after the apparatus removal. Bone formation was studied radiographically. Muscle preparations were examined histologically and stereomicroscopically. Results There was a threefold reduction in the distraction time in both groups. Consolidation took 13.83±4.02 days in group 1 and 33.7±2.4 days in group 2. Muscle macropreparations of the experimental limb in group 1 at study time points did not show significant differences from intact tissues. Muscle histostructure in both groups was characterized by activation of angiogenesis and myohistogenesis, but the volumetric density of microvessels in the lengthening phase was three times higher in group 1. Conclusion Combined technology significantly reduces the total lengthening procedure and does not compromise limb functions. Intramedullary HA-coated wires promote faster bone formation. The muscle was able to exhibit structural adaptation and plasticity of a restitution type.

(−)-α-Bisabolol reduces nociception and trigeminal central sensitisation in acute orofacial neuropathic pain induced by infraorbital nerve injury

Neuropathic orofacial pain conditions represent a challenge to diagnose and treat. Natural substances are promising therapeutic options for the control of pain. AimsThis study aimed to examine whether (−)-α-bisabolol (BISA), a natural terpene, can attenuate nociceptive behaviour and central sensitisation in a rodent model of trigeminal neuropathic pain. Materials and methodsInfraorbital nerve transection (IONX) or sham operation was performed in adult male rats. Head withdrawal thresholds as a measure of facial mechanical sensitivity were tested with von Frey monofilaments applied bilaterally to the facial vibrissal pad pre-operatively (baseline) and then post-operatively before and at 60, 120, 240 and 360 min after administration of vehicle control per oris (p.o.) or BISA (200 mg/kg p.o.) (n = 8/group). Effects of BISA or vehicle on the activity of nociceptive neurons recorded in the medullary dorsal horn (MDH) were tested on post - operative day 8–10. ANOVA followed by post-hoc Bonferroni tested for statistically significant differences (p < 0.05) across study groups and time points. Key findingsIONX animals (but not sham or naïve animals) showed post-operative facial mechanical hypersensitivity that was unaffected by vehicle. However, administration of BISA at post-operative day 7 significantly reversed the mechanical hypersensitivity in IONX rats; this effect lasted for at least 6 h. BISA also attenuated IONX-induced central sensitisation of MDH nociceptive neurons, as reflected in reversal of their reduced activation thresholds, increased responses to graded mechanical stimuli and enhanced spontaneous activity. SignificanceBISA may attenuate nociceptive behaviour and central sensitisation in a rat model of acute trigeminal neuropathic pain.

Assessment of the healthy worker survivor effect in the relationship between psychosocial work-related factors and hypertension

ObjectivesThe healthy worker survivor effect (HWSE) usually leads to underestimation of the effects of harmful occupational exposures. HWSE is characterised by the concomitance of three associations: (1) job status–subsequent exposure,...

Expression of alpha-amylase and growth-related genes during early larval developmental stages of Clarias magur

To understand the carbohydrate utilization ability during developmental stages of Clarias magur, the mRNA levels and enzyme activity of amylase were studied. Furthermore, the transcript levels of some important growth genes like growth hormone (GH), insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein (IGFBP) were evaluated. The enzymatic activity and mRNA expression of alpha-amylase along with expression of growth-related genes were examined from hatching until 34 days post-hatching (dph) by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Subsequently, mRNA expression pattern revealed the significantly (P < .05) high transcript level of alpha-amylase during early stages and early peaks were found at 3 to 6 dph, later the expression decreased till the end of experiment. Growth-related genes like GH, IGF-I and IGFBP showed a variable level of mRNA expression pattern from 0 dph to 34 dph. However, there was no significant difference (P > .05) in the mRNA expression of growth-related genes among the different time points of the present study. Moreover, the amylase activity revealed almost same pattern as that of its mRNA expression. In general, the present results suggested that C. magur has the ability to utilize the digestible carbohydrates during the early stages and can be helpful in developing low cost feeds for larvae.

The Support for New Mums Project: A protocol for a pilot randomized controlled trial designed to test a postnatal psychoeducation smartphone application.

To report a pilot trial protocol for testing the effectiveness of the Support for New Mums smartphone application in a cohort of first-time mothers. A pilot/feasibility randomized controlled trial using a two-group pre-test and repeated post-test design. This protocol follows the Standard Protocol Items: Recommendations for Intervention Trials (SPIRIT) guidelines. The Intervention group will receive access to the smartphone application for 6weeks post birth. Both Intervention and control groups will receive standardized institutional postnatal care services. Trial funding was gained from respective grant sponsors in May and November 2016. The Support for New Mums smartphone application could be a novel method for addressing the gap in provision of postpartum care services providing psychoeducation and improving maternal parental self-efficacy for Australian childbearing women. Australian New Zealand Clinical Trials Registry ACTRN12618001580268.

QIM19-144: Health-Related Quality of Life and Stress Level in Patients After Thyroid Resection Due to Cancer Depends on Patients’ Knowledge About Their Disease and Treatment Plan: Preliminary Results

Background: Relevant information is a prerequisite for patients to acquire enough knowledge to enable them to be actively involved in shared decision making, to comply with the treatment plan, and to understand what are potential benefits and side-effects of proposed therapy. Aim: The aim of this prospective, longitudinal study was to investigate whether cancer patients’ level of knowledge about their disease and treatment was associated with their health-related quality of life (HRQOL), particularly stress level. Patients and Methods: From October 2017 till September 2018, 41 patients aged 26–69 (median, 42) years referred for curative thyroidectomy were included into the study. EORTC QLQ-INFO25 questionnaire was used to measure level of patients’ knowledge about their disease and treatment, while thyroid-specific HRQOL was measured using Polish version of ThyPRO questionnaire and stress level by COPE Inventory. Assessments were done directly before the surgery (T1), 3 months after (T2), and 6 months after the treatment (T3). Results: The information about the disease (T1: 39.2, T2: 47.6, T3: 52.8; P=.024), information about treatment (T1: 27.2, T2: 42.6, T3: 60.8; P&lt;.001), information about what patients can do to help themselves (T1: 22.6, T2: 39.4, T3: 52.2; P=.037), and satisfaction with the received information (T1: 32.6, T2: 41.0, T3: 49.7; P=.049) increased significantly during the study period. Moreover, the proportion of patients who wished they had received more information decreased from 59.4% at T1 to 22.8% at T3 (P&lt;.001). Almost all of HRQOL domain scores were increasing in the consecutive time points with respect to role-physical (T1: 72.7, T2: 79.2, T3: 80.7; P=.003), role-emotional (T1: 77.6, T2: 82.8, T3: 88.9; P=.001), general health (T1: 52.7, T2: 60.2, T3: 63.4; P&lt;.001), physical functioning (T1: 69.7, T2: 77.8, T3: 79.4; P=.011), social functioning (T1: 82.7, T2: 88.9, T3: 89.4; P=.047), and vitality (T1: 69.3, T2: 72.8, T3: 79.9; P&lt;.001). Based on COPE Inventory, from the relative scores on various coping strategies in each time point, the 5 most common coping strategies adopted were active coping, planning, suppression of competing activities, focus on emotions, and positive reinterpretation and growth. There was significant correlation between EORTC QLQ-INFO25, ThyPRO, and COPE Inventory, in particular study time point (P&lt;.001). Conclusions: Patients’ knowledge increased significantly during the study period, and they reported that they felt better informed and were more satisfied with the information. This significantly influenced improvement of HRQOL and stress reduction. Psychological outcome must be considered as important measurement assessing treatment effect.

Effect of anticoagulant treatment on pain in distal deep vein thrombosis: an ancillary analysis from the cactus trial

Essentials Management of patients with calf deep vein thrombosis remains controversial. We conducted a post-hoc analysis of a placebo controlled LMWH randomized clinical trial. Pain was assessed using visual analogue scale at inclusion, one and six weeks. There was no difference in pain control between the two arms. SUMMARY: Background The optimal management of distal deep vein thrombosis (DVT) is highly debated. The only available placebo-controlled trial suggested the absence of clear benefit of anticoagulation. Many physicians feel that, beyond preventing thromboembolic complications, anticoagulation with low-molecular-weight heparin (LMWH) has the potential to improve pain control. Objectives To analyze whether LMWHs decrease pain in patients with distal deep vein thrombosis. Patients and methods Two-hundred and fifty-two patients included in a multicenter, placebo-controlled, randomized clinical trial of LMWH in patients with acute distal DVT and who were asked to rate their pain at inclusion and at each medical visit, using a visual analogue pain scale (VAS). Results One hundred and thirty patients were randomized in the therapeutic nadroparin arm and 122 patients were randomized in the placebo arm. Mean VAS values were 4.6 (standard deviation [SD] 2.5) at inclusion, 2.1 (SD 2.0) at 1week and 0.4 (SD 1.2) at 6weeks. We calculated the individual variation in VAS between inclusion and 1week in patients in whom VAS was available at the two study time-points. There was no difference in the mean VAS reduction between patients treated with therapeutic nadroparin (n=106) and with placebo (n=109): -2.6 (SD 2.4) vs. -2.3 (SD 2.0) after 1week and -4.4 (SD 2.8) vs. -4.0 (SD 2.4) after 6weeks, respectively. The use of compression stockings was associated with a reduction in pain. Conclusion These data suggests that LMWH use does not improve pain control as compared with placebo in patients with acute distal DVT.

Post-radiotherapy apparent diffusion coefficient (ADC) in children and young adults with high-grade gliomas and diffuse intrinsic pontine gliomas

Objectives: Diffusion-weighted magnetic resonance imaging (DW-MRI) offers potential to monitor response and predict survival in high-grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG). We hypothesized that post-radiotherapy DW-MRI may provide prognostic imaging biomarkers in children and young adults with these tumors. Methods: Patients aged ≤21 years diagnosed between 2005 and 2012 were eligible. The tumor median apparent diffusion coefficient (ADC) and its 5th percentile (C5-ADC) were determined at the first post-radiotherapy scan and at the time of radiological progression. DW-MRI parameters were correlated with survival endpoints, temozolomide use and pseudoprogression, when it occurred. Results: Out of 40 patients (20 HGG, 20 DIPG), 23 had evaluable DW-MRI post-radiotherapy and 25 at radiological progression. There were 6 episodes of pseudoprogression. Hazard ratios (95%CI) for progression-free survival were 0.998 (0.993–1.003) for median ADC and 1.003 (0.996–1.010) for C5-ADC. Hazard ratios (95%CI) for overall survival were 1.0009 (0.996–1.006) for median ADC and 0.998 (0.992–1.004) for C5-ADC. Post-radiotherapy median and C5-ADC values were not significantly different between patients treated with radiotherapy alone versus radiotherapy/temozolomide. The median and C5-ADC values were not significantly different at the time of pseudoprogression compared to those at tumor progression. Conclusions: Post-radiotherapy median ADC and C5-ADC were not prognostic, nor able to differentiate radiosensitization with temozolomide or occurrence of pseudoprogression in this cohort of HGG and DIPG patients. Further exploration of alternative DW parameters, study timepoints or data modeling may contribute to the development of prognostic/predictive imaging biomarkers for children and young adults with HGG or DIPG.

Fecal Microbiota Analysis in Patients Going through a Depressive Episode during Treatment in a Psychiatric Hospital Setting.

Rationale: There is a worldwide prevalence of generalized anxiety and major depressive disorders (MDD). Gut–brain axis dysfunction, antibacterial activity, and modulatory effects of antidepressants toward intestinal bacteria have been shown both in vitro and in vivo. Objectives: In this study, we aimed to investigate the effects of hospital stay, including escitalopram administration, on gut microbiota in patients with depressive episodes. Methods: After admission to the hospital and 7-days washout from all medications the composition of fecal microbiota samples was evaluated at baseline (W0) and after 6 weeks (W6), using 16S rRNA sequencing. The study was conducted on 17 inpatients (52.9% females), who followed the same daily hospital routine, including a standard diet and received 5–20 mg daily doses of escitalopram. Results: At the end of treatment (W6), no change was observed in the Chao1 index. However, Shannon (median (Q1–Q3): W0 2.78 (2.67–3.02) vs. W6 3.11 (2.80–3.30)), and inverse Simpson (median (Q1–Q3): W0 9.26 (7.26–13.76) vs. W6 12.13 (9.17–15.73)) indices increased significantly compared to baseline values (False Discovery Rate p (q) = 0.031 and q = 0.011, respectively). We also found that between-subject W0 Bray–Curtis dissimilarities were significantly higher than W0–W6 within-subject dissimilarities (median (Q1–Q3): 0.68 (0.56–0.77) vs. 0.38 (0.35–0.52), two sided Mann–Whitney test p < 0.00001. The within-subject dissimilarities did not depend on sex, age, BMI, illness duration and a daily dose of escitalopram. No significant differences between taxa levels, at the studied time points, were observed when adjusted for multiple hypotheses testing procedures. Conclusions: We conclude that a six-week treatment in a psychiatric hospital setting resulted in increased alpha biodiversity in fecal microbiota, however its causal relationship with patients’ mental health was not proved. We have also found that individual microbiome stability was not affected by hospitalization.

Brief Report: Gut Structural Damage: an Ongoing Process in Chronically Untreated HIV Infection.

To investigate the longitudinal changes of gut structural damage in chronically untreated HIV infection. This is a 96-week prospective, single-site, cohort study of antiretroviral therapy-naive HIV-infected participants. Intestinal fatty acid-binding proteins (I-FABP) were used as a surrogate marker of gut structural damage. We assessed changes in I-FABP over 96 weeks and examined the associations between I-FABP, HIV variables, and inflammation. Spearman's correlations and linear mixed-effect models were used to study relationships among variables. A total of 63 HIV-infected, antiretroviral therapy-naive patients were included in this analysis. At baseline, 76% were male; 62% were African American, with median age and body mass index of 40 years and 27 kg/m, respectively. Median HIV-RNA and CD4 T-cell counts were 5520 copies per milliliter and 588 cells per mm, respectively. I-FABP significantly increased from baseline to week 96 (mean change +333.9 pg/mL; P = 0.03), and this increase was associated with viral replication (rho = +0.4; P = 0.03). I-FABP levels were found to be associated with markers of inflammation: sTNFR-II (rho = 0.4, P = 0.02) and sVCAM-1 (rho = 0.04; P < 0.01) at all study time points. Lower baseline CD4 T-cell counts was found to be independently associated with I-FABP progression after adjusting for baseline characteristic variables (P = 0.02). Gut structural damage is an ongoing process in the chronic phase of untreated HIV infection and is largely dependent on viral replication. I-FABP was found to be associated with worse immune function, increased inflammation, and viremia in chronically untreated HIV infection, supporting its role as a biomarker of intestinal barrier dysfunction.

Inequalities in health and health behaviours between couple and lone mothers before and during the financial crisis in Spain (2003-2012).

Lone mothers report worse health and adopt more risky health behaviours than couple mothers, as largely documented in several European countries, but not deeply in Spain. The primary aim of this study was to identify the possible existence of inequalities in health and health behaviours between couple and lone mothers in Spain by occupational social class and employment status. A second aim was to explore whether any inequalities were influenced by the economic crisis beginning in 2008, analysing changes in inequalities between 2003–2004 and 2011–2012.Two waves of the cross-sectional Spanish National Health Survey data were used. Analyses were restricted to mothers aged 16–64 years, with at least one child aged 18 years or younger. The sample consisted of 2982 mothers in 2003–2004 and 3070 in 2011–2012, representing more than 80% of couple mothers. Two health outcomes and two health behaviour measurements were used. Robust Poisson regression was run to estimate inequalities between couple and lone mothers, calculating prevalence ratios adjusted by age and stratified by social class and employment status.We found inequalities in health and health behaviours between couple and lone mothers in Spain amongst the manual social class, with lone mothers reporting a more than 30% higher prevalence of poor self-perceived health and being smoker in both time points of study compared with couple mothers. Furthermore, lone mothers were at 50% higher risk of having at least one selected chronic condition and 86% higher probability of sleeping less than 6 hours/day in 2011–2012 This study could not confirm that inequalities between couple and lone mothers changed in Spain during the study period, although some patterns were noticeable. Inequalities pointed towards an increase amongst mothers in the manual social class with paid employment, while inequalities amongst unemployed mothers (both manual and non-manual social class) pointed towards a decrease.