Effects of a Brown Beans Evening Meal on Metabolic Risk Markers and Appetite Regulating Hormones at a Subsequent Standardized Breakfast: A Randomized Cross-Over Study

Background

Dietary prevention strategies are increasingly recognized as essential to combat the current epidemic of obesity and related metabolic disorders. The purpose of the present study was to evaluate the potential prebiotic effects of indigestible carbohydrates in Swedish brown beans (Phaseolus vulgaris var. nanus) in relation to cardiometabolic risk markers and appetite regulating hormones.

Methods

Brown beans, or white wheat bread (WWB, reference product) were provided as evening meals to 16 healthy young adults in a randomised crossover design. Glucose, insulin, appetite regulatory hormones, GLP-1, GLP-2, appetite sensations, and markers of inflammation were measured at a following standardised breakfast, that is at 11 to 14 h post the evening meals. Additionally, colonic fermentation activity was estimated from measurement of plasma short chain fatty acids (SCFA, including also branched chain fatty acids) and breath hydrogen (H₂) excretion.

Results

An evening meal of brown beans, in comparison with WWB, lowered blood glucose (−15%, p<0.01)- and insulin (−16%, p<0.05) responses, increased satiety hormones (PYY 51%, p<0.001), suppressed hunger hormones (ghrelin −14%, p<0.05), and hunger sensations (−15%, p = 0.05), increased GLP-2 concentrations (8.4%, p<0.05) and suppressed inflammatory markers (IL-6 −35%, and IL-18 −8.3%, p<0.05) at a subsequent standardised breakfast. Breath H₂ (141%, p<0.01), propionate (16%, p<0.05), and isobutyrate (18%, P<0.001) were significantly increased after brown beans compared to after WWB, indicating a higher colonic fermentative activity after brown beans.

Conclusions

An evening meal with brown beans beneficially affected important measures of cardiometabolic risk and appetite regulatory hormones, within a time frame of 11–14 h, in comparison to a WWB evening meal. Concentrations of plasma SCFA and H₂ were increased, indicating involvement of colonic fermentation. Indigestible colonic substrates from brown beans may provide a preventive tool in relation to obesity and the metabolic syndrome.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01706042","term_id":"NCT01706042"}}NCT01706042     

Effects of Unfermented and Fermented Whole Grain Rye Crisp Breads Served as Part of a Standardized Breakfast,on Appetite and Postprandial Glucose and Insulin Responses: A Randomized Cross-over Trial

Background

Whole grain rye products have been shown to increase satiety and elicit lower postprandial insulin response without a corresponding change in glucose response compared with soft refined wheat bread. The underlying mechanisms for these effects have not been fully determined The primary aim of the study was to investigate if whole grain rye crisp bread compared to refined wheat crisp bread, elected beneficial effects on appetite and postprandial insulin response, similarly as for other rye products.

Methods

In a randomized cross-over trial, 23 healthy volunteers, aged 27-70 years, BMI 18-31.4 kg/m², were served a standardized breakfast with unfermented whole grain rye crisp bread (uRCB), fermented whole grain rye crisp bread (RCB) or refined wheat crisp bread (WCB), Appetite was measured using a visual analogue scale (VAS) until 4 h after breakfast. Postprandial glucose and insulin were measured at 0-230 min. Breads were chemically characterized including macronutrients, energy, dietary fiber components, and amino acid composition, and microstructure was characterized with light microscopy.

Results

Reported fullness was 16% higher (P<0.001), and hunger 11% and 12% lower (P<0.05) after ingestion of uRCB and RCB, respectively, compared with WCB. Postprandial glucose response did not differ significantly between treatments. Postprandial insulin was 10% lower (P<0.007) between 0-120 min but not significantly lower between 0-230 min for RCB compared with WCB. uRCB induced 13% (P<0.002) and 17% (P<0.001) lower postprandial insulin response between 0-230 min compared with RCB and WCB respectively.

Conclusion

Whole grain rye crisp bread induces higher satiety and lower insulin response compared with refined wheat crisp bread. Microstructural characteristics, dietary fiber content and composition are probable contributors to the increased satiety after ingestion of rye crisp breads. Higher insulin secretion after ingestion of RCB and WCB compared with uRCB may be due to differences in fiber content and composition, and higher availability of insulinogenic branched chain amino acids.

Trial Registration

ClinicalTrials.gov NCT02011217     

Phenotyping of UGT1A1 Activity Using Raltegravir Predicts Pharmacokinetics and Toxicity of Irinotecan in FOLFIRI

Background

Irinotecan toxicity correlates with UGT1A1 activity. We explored whether phenotyping UGT1A1 using a probe approach works better than current genotyping methods.

Methods

Twenty-four Asian cancer patients received irinotecan as part of the FOLFIRI regimen. Subjects took raltegravir 400 mg orally and intravenous midazolam 1 mg. Pharmacokinetic analyses were performed using WinNonLin and NONMEM. Genomic DNA was isolated and screened for the known genetic variants in UGT1A1 and CYP3A4/5.

Results

SN-38G/SN-38 AUC ratio correlated well with Raltegravir glucuronide/ Raltegravir AUC ratio (r = 0.784 p<0.01). Midazolam clearance correlated well with irinotecan clearance (r = 0.563 p<0.01). SN-38 AUC correlated well with Log10Nadir Absolute Neutrophil Count (ANC) (r = -0.397 p<0.05). Significant correlation was found between nadir ANC and formation rate constant of raltegravir glucuronide (r = 0.598, P<0.005), but not UGT1A1 genotype.

Conclusion

Raltegravir glucuronide formation is a good predictor of nadir ANC, and can predict neutropenia in East Asian patients. Prospective studies with dose adjustments should be done to develop raltegravir as a probe to optimize irinotecan therapy.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00808184","term_id":"NCT00808184"}}NCT00808184     

Risk Factors for Death in 632 Patients with Sickle Cell Disease in the United States and United Kingdom

Background

The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial.

Methods and Results

We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)≥3.0 m/s cuttof, which has a 67–75% positive predictive value for mean pulmonary artery pressure ≥25 mm Hg was used. Among 572 subjects, 11.2% had TRV≥3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV≥3.0 m/sec. At 24 months the cumulative survival was 83% with TRV≥3.0 m/sec and 98% with TRV<3.0 m/sec (p<0.0001). The hazard ratios for death were 11.1 (95% CI 4.1–30.1; p<0.0001) for TRV≥3.0 m/sec, 4.6 (1.8–11.3; p = 0.001) for NT-proBNP≥160 pg/mL, and 14.9 (5.5–39.9; p<0.0001) for both TRV≥3.0 m/sec and NT-proBNP≥160 pg/mL. Age >47 years, male gender, chronic transfusions, WHO class III–IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death.

Conclusions

A TRV≥3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable.

The study is registered in ClinicalTrials.gov with identifier

{"type":"clinical-trial","attrs":{"text":"NCT00492531","term_id":"NCT00492531"}}NCT00492531     

Association of Hematological Variables with Team-Sport Specific Fitness Performance

Purpose

We investigated association of hematological variables with specific fitness performance in elite team-sport players.

Methods

Hemoglobin mass (Hb_mass) was measured in 25 elite field hockey players using the optimized (2 min) CO-rebreathing method. Hemoglobin concentration ([Hb]), hematocrit and mean corpuscular hemoglobin concentration (MCHC) were analyzed in venous blood. Fitness performance evaluation included a repeated-sprint ability (RSA) test (8 x 20 m sprints, 20 s of rest) and the Yo-Yo intermittent recovery level 2 (YYIR2).

Results

Hb_mass was largely correlated (r = 0.62, P<0.01) with YYIR2 total distance covered (YYIR2_TD) but not with any RSA-derived parameters (r ranging from -0.06 to -0.32; all P>0.05). [Hb] and MCHC displayed moderate correlations with both YYIR2_TD (r = 0.44 and 0.41; both P<0.01) and RSA sprint decrement score (r = -0.41 and -0.44; both P<0.05). YYIR2_TD correlated with RSA best and total sprint times (r = -0.46, P<0.05 and -0.60, P<0.01; respectively), but not with RSA sprint decrement score (r = -0.19, P>0.05).

Conclusion

Hb_mass is positively correlated with specific aerobic fitness, but not with RSA, in elite team-sport players. Additionally, the negative relationships between YYIR2 and RSA tests performance imply that different hematological mechanisms may be at play. Overall, these results indicate that these two fitness tests should not be used interchangeably as they reflect different hematological mechanisms.     

Serum Dehydroepiandrosterone Sulphate Concentration Is Not a Predictive Factor in IVF Outcomes before the First Cycle of GnRH Agonist Administration in Women with Normal Ovarian Reserve

Objective

The aim of our study was to determine whether serum dehydroepiandrosterone sulphate (DHEAS) concentration and the models incorporating it could help clinicians to predict IVF outcomes in women with normal ovarian reserve undergoing their first long protocol.

Study Design

We performed a retrospective analysis of 459 women undergoing cycles of intracytoplasmic sperm injection (ICSI) for the first time in a long GnRH agonist protocol.

Results

Embryo transfer was performed in 407 women (88.7%). The fertilisation rate was 78.6%. The clinical pregnancy rate was 44.8% per started cycle and 50.6% per embryo transfer. Our univariate model revealed that the best predictors of clinical pregnancy were the number of mature oocytes, the number of embryos transferred and the number of good quality embryos, account for the clinical parameters that reflect ovarian reserve the best being AMH level and AFC. DHEAS did not predict clinical pregnancy (OR 1.001, 95% CI, 0.999–1.004). After adjusting for the number of embryos transferred and class of embryos in a multivariate model, the best predictors were age (OR 0.918, 95% CI, 0.867–0.972) and AFC (OR 1.022, 95% CI, 0.992–1.053). Serum DHEAS levels were positively correlated with AFC (r = 0.098, P<0.039) and testosterone levels (r = 0.371, P<0.001), as well as the number of mature oocytes (r = 0.109, P<0.019); serum DHEAS levels were negatively correlated with age (r = -0.220, P<0.001), follicle-stimulating hormone (FSH), (r = -0.116, P<0.015) and sex hormone-binding globulin (SHBG), (r = -0.193, P<0.001).

Conclusions

DHEAS concentration (in addition to the known factors of ovarian reserve) does not predict clinical pregnancy in women with normal ovarian reserve who are undergoing ICSI.     

Effects of High Doses of Cholecalciferol in Normal Subjects: A Randomized Double-Blinded,Placebo-Controlled Trial

Background

Vitamin D repletion with high doses of vitamin D is often recommended to patients and healthy subjects. The safety, especially concerning changes in urinary calcium excretion is of great importance.

Methods

In a double-blinded, placebo-controlled study in 40 healthy volunteers, we examined the changes in mineral metabolism during supplementation with 3000 IU of oral cholecalciferol daily during 4 months.

Results

Both 25(OH)vitamin D and 1,25(OH)₂vitamin D increased significantly in the active treated group as compared to the placebo group (186% versus 14% (P<0.001) and 28% versus – 8% (P<0.001)). No change was observed in urinary calcium excretion in the active group compared to the placebo group (P = 0.891). Fibroblast growth factor 23 increased significantly by 10% (P<0.018) in the active group. However, there was no difference in changes in FGF23 between treatment groups (P = 0.457).

Conclusion

High dose cholecalciferol significantly increases 25(OH)vitamin D and 1,25(OH)₂vitamin D levels compared to placebo. No changes in urinary calcium excretion or other measured components of the mineral metabolism were found between groups.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00952562","term_id":"NCT00952562"}}NCT00952562.     

Effects of Acute Endurance Exercise Performed in the Morning and Evening on Inflammatory Cytokine and Metabolic Hormone Responses

Purpose

To compare the effects of endurance exercise performed in the morning and evening on inflammatory cytokine responses in young men.

Methods

Fourteen healthy male participants aged 24.3 ± 0.8 years (mean ± standard error) performed endurance exercise in the morning (0900–1000 h) on one day and then in the evening (1700–1800 h) on another day with an interval of at least 1 week between each trial. In both the morning and evening trials, the participants walked for 60 minutes at approximately 60% of the maximal oxygen uptake (V·O2max) on a treadmill. Blood samples were collected to determine hormones and inflammatory cytokines at pre-exercise, immediately post exercise, and 2 h post exercise.

Results

Plasma interleukin (IL)-6 and adrenaline concentrations were significantly higher immediately after exercise in the evening trial than in the morning trial (P < 0.01, both). Serum free fatty acids concentrations were significantly higher in the evening trial than in the morning trial at 2 h after exercise (P < 0.05). Furthermore, a significant correlation was observed between the levels of IL-6 immediately post-exercise and free fatty acids 2 h post-exercise in the evening (r = 0.68, P < 0.01).

Conclusions

These findings suggest that the effect of acute endurance exercise in the evening enhances the plasma IL-6 and adrenaline concentrations compared to that in the morning. In addition, IL-6 was involved in increasing free fatty acids, suggesting that the evening is more effective for exercise-induced lipolysis compared with the morning.     

Nonapnea Sleep Disorders in Patients Younger than 65 Years Are Significantly Associated with CKD: A Nationwide Population-Based Study

Background

Nonapnea sleep disorders (NASD) and sleep-related problems are associated with poor health outcomes. However, the association between NASD and the development and prognosis of chronic kidney disease (CKD) has not been investigated thoroughly. We explored the association between CKD and NASD in Taiwan.

Methods

We conducted a population-based study using the Taiwan National Health Insurance database with1,000,000 representative data for the period from January 1, 2000 to December 31, 2009. We investigated the incidence and risk of CKD in 7,006 newly diagnosed NASD cases compared with 21,018 people without NASD matched according to age, sex, index year, urbanization, region, and monthly income at a 1:3 ratio.

Results

The subsequent risk of CKD was 1.48-foldhigher in the NASD cohort than in the control cohort (95% confidence interval [CI] = 1.26–1.73, p< 0.001). Men, older age, type 2 diabetes mellitus, and gout were significant factors associated with the increased risk of CKD (p< 0.001). Among different types of NASDs, patients with insomnia had a 52% increased risk of developing CKD (95%CI = 1.23–1.84; P<0.01), whereas patients with sleep disturbance had a 49%increased risk of subsequent CKD (95% CI = 1.19–1.87; P<0.001). Younger women (aged < 65 years) were at a high risk of CKD with NASD (adjusted hazard ratio, [HR] = 1.81; 95% CI = 1.35–2.40, p< 0.001).

Conclusions

In this nationwide population-based cohort study, patients with NASD, particularly men of all ages and women aged younger than 65 years, were at high risk of CKD.     

Comparison of Early Changes in Ocular Surface and Inflammatory Mediators between Femtosecond Lenticule Extraction and Small-Incision Lenticule Extraction

Purpose

To evaluate the short-term changes in ocular surface measures and tear inflammatory mediators after femtosecond lenticule extraction (FLEx) and small-incision lenticule extraction (SMILE) procedures.

Methods

Eighteen subjects (18 eyes) underwent FLEx and 23 subjects (23 eyes) underwent SMILE in this single-center and prospective study. Central corneal sensitivity, Schirmer I test (SIT), noninvasive tear breakup time (NI-TBUT), tear meniscus height, corneal fluorescein (FL) staining, and ocular surface disease index (OSDI) were assessed in all patients. Concentrations of interleukin-1α (IL-1α), tumor necrosis factor-α (TNF-α), nerve growth factor (NGF), interferon-γ (IFN-γ), transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) in collected tears were measured by multiplex antibody microarray.

Results

Central corneal sensitivity was reduced in both groups, but the scores in the SMILE group were higher than those in the FLEx group at all time points postoperatively (P<0.01). Lower FL scores and longer NI-BUT were observed in the SMILE group 1 week after surgery (P<0.05). OSDI scores in both groups increased rapidly at 1 day and 1 week postoperatively, then returned to their preoperative levels within 1 month (P<0.05). There were no significant differences in SIT or tear meniscus height between the two groups. Lower and faster recovery of tear NGF, TGF-β1 and IL-1α concentration were found in the SMILE group compared to the FLEx group postoperatively. No significant difference was found in tear TNF-α, IFN-γ and MMP-9 for either group before or after surgery. Tear NGF, TGF-β1 and IL-1α show a correlation with ocular surface changes after FLEx or SMILE surgery.

Conclusion

SMILE has superiority over FLEx in early ocular surface changes and NGF, TGF-β1 and IL-1α may contribute to the process of ocular surface recovery.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02540785","term_id":"NCT02540785"}}NCT02540785     

Differential Acute Postprandial Effects of Processed Meat and Isocaloric Vegan Meals on the Gastrointestinal Hormone Response in Subjects Suffering from Type 2 Diabetes and Healthy Controls: A Randomized Crossover Study

Background

The intake of meat, particularly processed meat, is a dietary risk factor for diabetes. Meat intake impairs insulin sensitivity and leads to increased oxidative stress. However, its effect on postprandial gastrointestinal hormone (GIH) secretion is unclear. We aimed to investigate the acute effects of two standardized isocaloric meals: a processed hamburger meat meal rich in protein and saturated fat (M-meal) and a vegan meal rich in carbohydrates (V-meal). We hypothesized that the meat meal would lead to abnormal postprandial increases in plasma lipids and oxidative stress markers and impaired GIH responses.

Methods

In a randomized crossover study, 50 patients suffering from type 2 diabetes (T2D) and 50 healthy subjects underwent two 3-h meal tolerance tests. For statistical analyses, repeated-measures ANOVA was performed.

Results

The M-meal resulted in a higher postprandial increase in lipids in both groups (p<0.001) and persistent postprandial hyperinsulinemia in patients with diabetes (p<0.001). The plasma glucose levels were significantly higher after the V-meal only at the peak level. The plasma concentrations of glucose-dependent insulinotropic peptide (GIP), peptide tyrosine-tyrosine (PYY) and pancreatic polypeptide (PP) were higher (p<0.05, p<0.001, p<0.001, respectively) and the ghrelin concentration was lower (p<0.001) after the M-meal in healthy subjects. In contrast, the concentrations of GIP, PYY and PP were significantly lower after the M-meal in T2D patients (p<0.001). Compared with the V-meal, the M-meal was associated with a larger increase in lipoperoxidation in T2D patients (p<0.05).

Conclusion/Interpretation

Our results suggest that the diet composition and the energy content, rather than the carbohydrate count, should be important considerations for dietary management and demonstrate that processed meat consumption is accompanied by impaired GIH responses and increased oxidative stress marker levels in diabetic patients.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01572402","term_id":"NCT01572402"}}NCT01572402     

Association of Pretreatment Anemia with Pathological Response and Survival of Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Population-Based Study

Background

Anemia related to adjuvant chemotherapy might predict compromised survival in patients with breast cancer. The present population-based study was to investigate the correlation of pretreatment anemia with pathological response and long-term prognosis of breast cancer patients receiving neoadjuvant chemotherapy (NCT).

Methods

From 1999 to 2011, a total of 655 patients with operable or locally advanced breast cancer who underwent NCT before definitive surgery were reviewed. The patients were subdivided into anemic (baseline hemoglobin (Hb)<12.0g/dL) and non-anemic (Hb≥12.0g/dL) groups. Comparison was made between anemic and non-anemic groups concerning the rate of pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS). Logistic and Cox regression models were utilized to determine the predictive value of pretreatment anemia in outcomes of patients undergoing NCT.

Results

166 women (25.3%) were anemic before treatment. Patients in the anemic group were less likely to achieve pCR in NCT than their non-anemic counterparts (odds ratio (OR) 0.428, 95% confidence interval (CI) 0.198–0.927, p = 0.031). Patients with baseline anemia displayed inferior 10-year RFS (59.1% vs 66.0%, p = 0.022 by log-rank), OS (75.3% vs 90.9%, p<0.001) and CSS (82.4% vs 94.4%, p<0.001) compared with those without. After adjustment for confounders, pretreatment anemia was demonstrated to correlate with elevated risk of relapse (hazard ratio (HR) 1.453, 95% CI 1.077–1.962, p = 0.015), cancer-specific mortality (HR 2.961, 95% CI 1.679–5.222, p<0.001) and all-cause mortality (HR 2.873, 95% CI 1.757–4.699, p<0.001).

Conclusions

Pretreatment anemia was associated with worse pathological response to NCT as well as survival status in breast cancer. Further studies are warranted to identify optimal interventions and improve the prognosis of this subgroup.     

Evaluating the Impact of Breastfeeding on Rotavirus Antigenemia and Disease Severity in Indian Children

Objectives

To evaluate the contribution of breastfeeding to Rotavirus (RV)-induced antigenemia and/or RNAemia and disease severity in Indian children (<2 yrs age).

Methods

Paired stool and serum samples were collected from (a) hospitalized infants with diarrhea (n = 145) and (b) healthy control infants without diarrhea (n = 28). Stool RV-antigen was screened in both groups by commercial rapid-test and enzyme immunoassay. The disease severity was scored and real-time-PCR was used for viral-load estimation. Serum was evaluated for RV-antigenemia by EIA and RV-RNAemia by RT-PCR. Data was stratified by age-group and breastfeeding status and compared.

Results

Presence of RV-antigenemia and RV-RNAemia was positively related with presence of RV in stool. Disease severity and stool viral-load was significantly associated with RV-antigenemia[(r = 0.74; CI:0.66 to 0.84; P<0.0001,R² = 0.59) and (r = -0.55; CI:-0.68 to -0.39; P<0.0001,R² = 0.31) respectively], but not with RV-RNAemia. There was significant reduction in RV-antigenemiarate in the breast-fed group compared to non-breastfed infants, especially in 0–6 month age group (P<0.001). Non-breastfed infants were at risk for RV-antigenemia with severe disease manifestations in form of high Vesikari scores correlating with high fever, more vomiting episodes and dehydration.

Conclusion

RV-antigenemia was common in nonbreastfed children with severe RV-diarrhea and correlated with stool RV-load and disease severity.     

Effects of Pre-Meal Drinks with Protein and Amino Acids on Glycemic and Metabolic Responses at a Subsequent Composite Meal

Background

Whey proteins have insulinogenic properties and the effect appears to originate from a specific postprandial plasma amino acid pattern. The insulinogenic effect can be mimicked by a specific mixture of the five amino acids iso, leu, lys, thr and val.

Objective

The objective was to evaluate the efficacy of pre-meal boluses of whey or soy protein with or without added amino acids on glycaemia, insulinemia as well as on plasma responses of incretins and amino acids at a subsequent composite meal. Additionally, plasma ghrelin and subjective appetite responses were studied.

Design

In randomized order, fourteen healthy volunteers were served a standardized composite ham sandwich meal with either water provided (250 ml) during the time course of the meal, or different pre-meal protein drinks (PMPD) (100 ml provided as a bolus) with additional water (150 ml) served to the meal. The PMPDs contained 9 g protein and were based on either whey or soy protein isolates, with or without addition of the five amino acids (iso, leu, lys, thr and val) or the five amino acids + arg.

Results

All PMPD meals significantly reduced incremental area for plasma glucose response (iAUC) during the first 60 min. All whey based PMPD meals displayed lower glycemic indices compared to the reference meal. There were no significant differences for the insulinemic indices. The early insulin response (iAUC 0–15 min) correlated positively to plasma amino acids, GIP and GLP-1 as well as to the glycemic profile. Additionally, inverse correlations were found between insulin iAUC 0–15 min and the glucose peak.

Conclusion

The data suggests that a pre-meal drink containing specific proteins/amino acids significantly reduces postprandial glycemia following a composite meal, in absence of elevated insulinemic excursions. An early phase insulinemic response induced by plasma amino acids and incretins appears to mediate the effect.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01586780","term_id":"NCT01586780"}}NCT01586780<{"type":"clinical-trial","attrs":{"text":"NCT01586780","term_id":"NCT01586780"}}NCT01586780>     

Incidence and Predictive Factors of Central Nervous System Dysfunction in Patients Consulting for Dengue Fever in Cayenne Hospital,French Guiana

Introduction

The frequency, the clinical characteristics, and the prognosis of dengue is highly variable. Dengue fever is associated with a range of neurological manifestations. The objective of the present study was to determine the incidence of neurological signs and their predictive factors using data from cases of dengue seen and followed in Cayenne Hospital during the Dengue 2 epidemic in 2013.

Methods

In 2013, a longitudinal study using data from all cases of dengue seen in Cayenne hospital was collected. Medical records used a standardized form to collect demographic information, clinical signs and biological results and the date at which they were present. The analysis used Cox proportional modeling to obtain adjusted Hazard ratios.

Results

A total of 1574 patients were included 221 of whom developed central nervous system signs. These signs were spontaneously resolutive. There were 9298person days of follow-up and the overall incidence rate for central nervous system signs was 2.37 per 100 person-days. The variables independently associated with central nervous system anomalies were headache, Adjusted Hazard ratio (AHR) = 1.9(95%CI = 1.4–2.6), bleeding AHR = 2 ((95%CI = 1.3–3.1), P = 0.001, abdominal pain AHR = 1.9 ((95%CI = 1.4–2.6), P<0.001, aches AHR = 2.1 ((95%CI = 1.5–2.9), P<0.001, and fatigue AHR = 1.5 ((95%CI = 1.3–1.7), P<0.001.

Discussion

Overall, the present study suggests that neurological signs of dengue are not exceptional even in patients without the most severe features of dengue. These manifestations were spontaneously resolutive. Here it was not possible to distinguish between encephalitis or encephalopathy. Further studies would require more in depth exploration of the patients.     

Cardiac Autonomic Nervous System Activation and Metabolic Profile in Young Children: The ABCD Study

Background

In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system activation and metabolic profile and its components in children at age of 5–6 years.

Methods

Cross-sectional data from an apparently healthy population (within the ABCD study) were collected at age 5–6 years in 1540 children. Heart rate (HR), respiratory sinus arrhythmia (RSA; parasympathetic activity) and pre-ejection period (PEP; sympathetic activity) were assessed during rest. Metabolic components were waist-height ratio (WHtR), systolic blood pressure (SBP), fasting triglycerides, glucose and HDL-cholesterol. Individual components, as well as a cumulative metabolic score, were analyzed.

Results

In analysis adjusted for child’s physical activity, sleep, anxiety score and other potential confounders, increased HR and decreased RSA were associated with higher WHtR (P< 0.01), higher SBP (p<0.001) and a higher cumulative metabolic score (HR: p < 0.001; RSA: p < 0.01). Lower PEP was only associated with higher SBP (p <0.05). Of all children, 5.6% had 3 or more (out of 5) adverse metabolic components; only higher HR was associated with this risk (per 10 bpm increase: OR = 1.56; p < 0.001).

Conclusions

This study shows that decreased parasympathetic activity is associated with central adiposity and higher SBP, indicative of increased metabolic risk, already at age 5–6 years.     

Fluctuations of Serum Neuron Specific Enolase and Protein S-100B Concentrations in Relation to the Use of Shunt during Carotid Endarterectomy

Objective

To evaluate the changes in serum neuron specific enolase and protein S-100B, after carotid endarterectomy performed using the conventional technique with routine shunting and patch closure, or eversion technique without the use of shunt.

Materials and Methods

Prospective non-randomized study included 43 patients with severe (>80%) carotid stenosis undergoing carotid endarterectomy in regional anesthesia. Patients were divided into two groups: conventional endarterectomy with routine use of shunt and Dacron patch (csCEA group) and eversion endarterectomy without the use of shunt (eCEA group). Protein S-100B and NSE concentrations were measured from peripheral blood before carotid clamping, after declamping and 24 hours after surgery.

Results

Neurologic examination and brain CT findings on the first postoperative day did not differ from preoperative controls in any patients. In csCEA group, NSE concentrations decreased after declamping (P<0.01), and 24 hours after surgery (P<0.01), while in the eCEA group NSE values slightly increased (P=ns), accounting for a significant difference between groups on the first postoperative day (P=0.006). In both groups S-100B concentrations significantly increased after declamping (P<0.05), returning to near pre-clamp values 24 hours after surgery (P=ns). Sub-group analysis revealed significant decline of serum NSE concentrations in asymptomatic patients shunted during surgery after declamping (P<0.05) and 24 hours after surgery (P<0.01), while no significant changes were noted in non-shunted patients (P=ns). Decrease of NSE serum levels was also found in symptomatic patients operated with the use of shunt on the first postoperative day (P<0.05). Significant increase in NSE serum levels was recorded in non-shunted symptomatic patients 24 hours after surgery (P<0.05).

Conclusion

Variations of NSE concentrations seemed to be influenced by cerebral perfusion alterations, while protein S-100B values were unaffected by shunting strategy. Routine shunting during surgery for symptomatic carotid stenosis may have the potential to prevent postoperative increase of serum NSE levels, a potential marker of brain injury.     

Urinary Biomarkers of Polycyclic Aromatic Hydrocarbons Are Associated with Cardiometabolic Health Risk

Background

Polycyclic aromatic hydrocarbons (PAH) are both man-made and naturally occurring environmental pollutants that may be related to cardiometabolic health risk.

Objective

To determine whether PAH is associated with obesity in the adult population and to examine whether urinary concentrations of PAH metabolites are associated with differences in how obesity relates to 3 or more risk factors for the metabolic syndrome (3RFMetS), type 2 diabetes (T2D), hypertension, and dyslipidemia.

Methods

A total of 4765 adult participants from the 2001–2008 National Health and Nutrition Examination Survey were examined. The association between 8 urinary hydroxylated PAH metabolites, obesity, and health were examined using weighted logistic regressions adjusting for age, sex, ethnicity, PIR, smoking status, and urinary creatinine.

Results

There was a positive dose-dependent association between obesity and 2-phenanthrene quintiles (P trend <0.0001). Contrarily, higher quintiles of 1-naphthalene were associated with lower risk of obesity (P trend = 0.0004). For a given BMI, those in the highest quintile of 2-naphthalene, 2-fluorene, 3-fluorene and 2-phenanthrene had a 66–80% greater likelihood of 3RFMetS (P≤0.05) compared to low levels. Higher quintiles of 1-naphthalene, 2-naphthalene, 2-phenanthrene and 1-pyrene were associated with a 78–124% greater likelihood of T2D (P≤0.05) compared to low levels while high 1-naphthalene, 2-naphthalene, 2-fluorene, 3-fluorene and 2-phenanthrene were associated with a 38–68% greater likelihood of dyslipidemia (P≤0.05) compared to lower levels. Finally, 2-naphthalene and 2-phenanthrene were positively associated with hypertension (P trend = 0.008 and P trend = 0.02 respectively).

Conclusions

PAH is related to obesity and the expression of a number of obesity-related cardiometabolic health risk factors. Future research is needed to bring to light the mechanistic pathways related to these findings.     

Low Ambient Temperature and Intracerebral Hemorrhage: The INTERACT2 Study

Background

Rates of acute intracerebral hemorrhage (ICH) increase in winter months but the magnitude of risk is unknown. We aimed to quantify the association of ambient temperature with the risk of ICH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2) participants on an hourly timescale.

Methods

INTERACT2 was an international, open, blinded endpoint, randomized controlled trial of patients with spontaneous ICH (<6h of onset) and elevated systolic blood pressure (SBP, 150–220 mmHg) assigned to intensive (target SBP <140 mmHg) or guideline-recommended (SBP <180 mmHg) BP treatment. We linked individual level hourly temperature to baseline data of 1997 participants, and performed case-crossover analyses using a distributed lag non-linear model with 24h lag period to assess the association of ambient temperature and risk of ICH. Results were presented as overall cumulative odds ratios (ORs) and 95% CI.

Results

Low ambient temperature (≤10°C) was associated with increased risks of ICH: overall cumulative OR was 1.37 (0.99–1.91) for 10°C, 1.92 (1.31–2.81) for 0°C, 3.13 (1.89–5.19) for -10°C, and 5.76 (2.30–14.42) for -20°C, as compared with a reference temperature of 20°C.There was no clear relation of low temperature beyond three hours after exposure. Results were consistent in sensitivity analyses.

Conclusions

Exposure to low ambient temperature within several hours increases the risk of ICH.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00716079","term_id":"NCT00716079"}}NCT00716079     

A Pilot Randomized Placebo Controlled Trial of Electroacupuncture for Women with Pure Stress Urinary Incontinence

Background

Acupuncture is a potential conservative therapy for women with stress urinary incontinence (SUI). There is limited evidence to support its effectiveness due to the poor quality of existing studies.

Methods

We performed a pilot randomized, controlled trial to preliminarily assess the efficacy of electroacupuncture (EA) in women with pure SUI. A total of 80 women with pure SUI were randomly assigned to receive EA with deep needling at BL33 and BL35 (n = 40) or sham EA with non-penetrating needling at sham acupoints (n = 40) three sessions per week for 6 weeks. The women were followed for 24 weeks. The primary outcome was the change from baseline in the amount of urine leakage measured by a 1-hour pad test after 6 weeks. The secondary outcomes included the 72-hour incontinence episode frequency (IEF), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score, and patient self-evaluation of therapeutic effect. Adverse events (AEs) were monitored throughout the trial.

Results

The median decrease from baseline of urine leakage measured by the 1-hour pad test was 2.5 g [interquartile range (IQR): 1.80–14.6 in the EA group, which was greater than the median decrease of 0.05 g (IQR: -2.80–+0.50) in the sham EA group after 6 weeks (p<0.01). The differences between groups in the decrease from baseline of 72-hour IEF became statistically significant at week 30 with a median decrease of 3.25 g (IQR: 1.25–5.69) in the EA group, and a median decrease of 1.00 g (IQR: -0.69–+2.88) in the sham EA group (p = 0.01). The participants in the EA group showed greater decreases in ICIQ-SF score and higher ratings in the help they received from the treatment than those in the sham EA group at weeks 6,18 and 30 (all p<0.05). No obvious AEs were observed in either group.

Conclusion

EA may effectively and safely relieve urinary incontinence symptoms and improve quality of life in women with pure SUI. EA demonstrated more than a placebo effect. Since this is a pilot study, results should be interpreted with caution.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02445573","term_id":"NCT02445573"}}NCT02445573.