A 4-Week Diet Low or High in Advanced Glycation Endproducts Has Limited Impact on Gut Microbial Composition in Abdominally Obese Individuals: The deAGEing Trial.

Dietary advanced glycation endproducts (AGEs), abundantly present in Westernized diets, are linked to negative health outcomes, but their impact on the gut microbiota has not yet been well investigated in humans. We investigated the effects of a 4-week isocaloric and macronutrient-matched diet low or high in AGEs on the gut microbial composition of 70 abdominally obese individuals in a double-blind parallel-design randomized controlled trial (NCT03866343). Additionally, we investigated the cross-sectional associations between the habitual intake of dietary dicarbonyls, reactive precursors to AGEs, and the gut microbial composition, as assessed by 16S rRNA amplicon-based sequencing. Despite a marked percentage difference in AGE intake, we observed no differences in microbial richness and the general community structure. Only the Anaerostipes spp. had a relative abundance >0.5% and showed differential abundance (0.5 versus 1.11%; p = 0.028, after low- or high-AGE diet, respectively). While the habitual intake of dicarbonyls was not associated with microbial richness or a general community structure, the intake of 3-deoxyglucosone was especially associated with an abundance of several genera. Thus, a 4-week diet low or high in AGEs has a limited impact on the gut microbial composition of abdominally obese humans, paralleling its previously observed limited biological consequences. The effects of dietary dicarbonyls on the gut microbiota composition deserve further investigation.

Using web search queries to monitor influenza-like illness: an exploratory retrospective analysis, Netherlands, 2017/18 influenza season.

BackgroundDespite the early development of Google Flu Trends in 2009, standards for digital epidemiology methods have not been established and research from European countries is scarce.AimIn this article, we study the use of web search queries to monitor influenza-like illness (ILI) rates in the Netherlands in real time.MethodsIn this retrospective analysis, we simulated the weekly use of a prediction model for estimating the then-current ILI incidence across the 2017/18 influenza season solely based on Google search query data. We used weekly ILI data as reported to The European Surveillance System (TESSY)  each week, and we removed the then-last 4 weeks from our dataset. We then fitted a prediction model based on the then-most-recent search query data from Google Trends to fill the 4-week gap ('Nowcasting'). Lasso regression, in combination with cross-validation, was applied to select predictors and to fit the 52 models, one for each week of the season.ResultsThe models provided accurate predictions with a mean and maximum absolute error of 1.40 (95% confidence interval: 1.09-1.75) and 6.36 per 10,000 population. The onset, peak and end of the epidemic were predicted with an error of 1, 3 and 2 weeks, respectively. The number of search terms retained as predictors ranged from three to five, with one keyword, 'griep' ('flu'), having the most weight in all models.DiscussionThis study demonstrates the feasibility of accurate, real-time ILI incidence predictions in the Netherlands using Google search query data.

Oral evening primrose oil and borage oil for eczema.

BACKGROUND: Eczema is a chronic inflammatory skin condition, which usually develops in early childhood. Many children outgrow this disorder as they reach secondary school age, and although It may improve with age, there is no cure. Constant itch makes life uncomfortable for those with this condition, no matter what age they are, so it may have a significant effect on a person's quality of life. Its prevalence seems to be increasing as populations move from rural locations to cities. Some people, who do not see an adequate improvement or fear side-effects of conventional medical products, try complementary alternatives to conventional treatment. This is a review of evening primrose oil (EPO) and borage oil (BO) taken orally (by mouth); these have been thought to be beneficial because of their gamma-linolenic acid content. OBJECTIVES: To assess the effects of oral evening primrose oil or borage oil for treating the symptoms of atopic eczema. SEARCH METHODS: We searched the following databases up to August 2012: Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 1946), EMBASE (from 1974), AMED (from 1985), and LILACS (from 1982). We also searched online trials registers and checked the bibliographies of included studies for further references to relevant trials. We corresponded with trial investigators and pharmaceutical companies to try to identify unpublished and ongoing trials. We performed a separate search for adverse effects of evening primrose oil and borage oil in November 2011. SELECTION CRITERIA: All randomised controlled, parallel, or cross-over trials investigating oral intake of evening primrose oil or borage oil for eczema. DATA COLLECTION AND ANALYSIS: Two review authors independently applied eligibility criteria, assessed risk of bias, and extracted data. We pooled dichotomous outcomes using risk ratios (RR), and continuous outcomes using the mean difference (MD). Where possible, we pooled study results using random-effects meta-analysis and tested statistical heterogeneity using both the Chi(²) test and the I(²) statistic test. We presented results using forest plots with 95% confidence intervals (CI). MAIN RESULTS: A total of 27 studies (1596 participants) met the inclusion criteria: 19 studies assessed evening primrose oil, and 8 studies assessed borage oil. For EPO, a meta-analysis of results from 7 studies showed that EPO failed to significantly increase improvement in global eczema symptoms as reported by participants on a visual analogue scale of 0 to 100 (MD -2.22, 95% CI -10.48 to 6.04, 176 participants, 7 trials) and a visual analogue scale of 0 to 100 for medical doctors (MD -3.26, 95% CI -6.96 to 0.45, 289 participants, 8 trials) compared to the placebo group.Treatment with BO also failed to significantly improve global eczema symptoms compared to placebo treatment as reported by both participants and medical doctors, although we could not conduct a meta-analysis as studies reported results in different ways. With regard to the risk of bias, the majority of studies were of low risk of bias; we judged 67% of the included studies as having low risk of bias for random sequence generation; 44%, for allocation concealment; 59%, for blinding; and 37%, for other biases. IMPLICATIONS FOR PRACTICE: Oral borage oil and evening primrose oil lack effect on eczema; improvement was similar to respective placebos used in trials. Oral BO and EPO are not effective treatments for eczema.In these studies, along with the placebos, EPO and BO have the same, fairly common, mild, transient adverse effects, which are mainly gastrointestinal.The short-term studies included here do not examine possible adverse effects of long-term use of EPO or BO. A case report warned that if EPO is taken for a prolonged period of time (more than one year), there is a potential risk of inflammation, thrombosis, and immunosuppression; another study found that EPO may increase bleeding for people on Coumadin® (warfarin) medication. IMPLICATIONS FOR RESEARCH: Noting that the confidence intervals between active and placebo treatment are narrow, to exclude the possibility of any clinically useful difference, we concluded that further studies on EPO or BO for eczema would be hard to justify.This review does not provide information about long-term use of these products.

Gender differences in patients with dizziness and unsteadiness regarding self-perceived disability, anxiety, depression, and its associations.

BACKGROUND: It is known that anxiety and depression influence the level of disability experienced by persons with vertigo, dizziness or unsteadiness. Because higher prevalence rates of disabling dizziness have been found in women and some studies reported a higher level of psychiatric distress in female patients our primary aim was to explore whether women and men with vertigo, dizziness or unsteadiness differ regarding self-perceived disability, anxiety and depression. Secondly we planned to investigate the associations between disabling dizziness and anxiety and depression. METHOD: Patients were recruited from a tertiary centre for vertigo and balance disorders. Participants rated their global disability as mild, moderate or severe. They filled out the Dizziness Handicap Inventory and the two subscales of the Hospital Anxiety Depression Scale (HADS). The HADS was analysed 1) by calculating the median values, 2) by estimating the prevalence rates of abnormal anxiety/depression based on recommended cut-off criteria. Mann-Whitney U-tests, Chi-square statistics and odds ratios (OR) were calculated to compare the observations in both genders. Significance values were adjusted with respect to multiple comparisons. RESULTS: Two-hundred and two patients (124 women) mean age (standard deviation) of 49.7 (13.5) years participated. Both genders did not differ significantly in the mean level of self-perceived disability, anxiety, depression and symptom severity. There was a tendency of a higher prevalence of abnormal anxiety and depression in men (23.7%; 28.9%) compared to women (14.5%; 15.3%). Patients with abnormal depression felt themselves 2.75 (95% CI: 1.31-5.78) times more severely disabled by dizziness and unsteadiness than patients without depression. In men the OR was 8.2 (2.35-28.4). In women chi-square statistic was not significant. The ORs (95% CI) of abnormal anxiety and severe disability were 4.2 (1.9-8.9) in the whole sample, 8.7 (2.5-30.3) in men, and not significant in women. CONCLUSIONS: In men with vertigo, dizziness or unsteadiness emotional distress and its association with self-perceived disability should not be underestimated. Longitudinal surveys with specific pre-defined co-variables of self-perceived disability, anxiety and depression are needed to clarify the influence of gender on disability, anxiety and depression in patients with vertigo, dizziness or unsteadiness.

A 4-week high-AGE diet does not impair glucose metabolism and vascular function in obese individuals.

BACKGROUNDAccumulation of advanced glycation endproducts (AGEs) may contribute to the pathophysiology of type 2 diabetes and its vascular complications. AGEs are widely present in food, but whether restricting AGE intake improves risk factors for type 2 diabetes and vascular dysfunction is controversial.METHODSAbdominally obese but otherwise healthy individuals were randomly assigned to a specifically designed 4-week diet low or high in AGEs in a double-blind, parallel design. Insulin sensitivity, secretion, and clearance were assessed by a combined hyperinsulinemic-euglycemic and hyperglycemic clamp. Micro- and macrovascular function, inflammation, and lipid profiles were assessed by state-of-the-art in vivo measurements and biomarkers. Specific urinary and plasma AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were assessed by mass spectrometry.RESULTSIn 73 individuals (22 males, mean ± SD age and BMI 52 ± 14 years, 30.6 ± 4.0 kg/m2), intake of CML, CEL, and MG-H1 differed 2.7-, 5.3-, and 3.7-fold between the low- and high-AGE diets, leading to corresponding changes of these AGEs in urine and plasma. Despite this, there was no difference in insulin sensitivity, secretion, or clearance; micro- and macrovascular function; overall inflammation; or lipid profile between the low and high dietary AGE groups (for all treatment effects, P > 0.05).CONCLUSIONThis comprehensive RCT demonstrates very limited biological consequences of a 4-week diet low or high in AGEs in abdominally obese individuals.TRIAL REGISTRATIONClinicaltrials.gov, NCT03866343; trialregister.nl, NTR7594.FUNDINGDiabetesfonds and ZonMw.

Exploratory factor analysis of the Dizziness Handicap Inventory (German version).

BACKGROUND: The Dizziness Handicap Inventory (DHI) is a validated, self-report questionnaire which is widely used as an outcome measure. Previous studies supported the multidimensionality of the DHI, but not the original subscale structure. The objectives of this survey were to explore the dimensions of the Dizziness Handicap Inventory - German version, and to investigate the associations of the retained factors with items assessing functional disability and the Hospital Anxiety and Depression Scale (HADS). Secondly we aimed to explore the retained factors according to the International Classification of Functioning, Disability and Health (ICF). METHODS: Patients were recruited from a tertiary centre for vertigo, dizziness or balance disorders. They filled in two questionnaires: (1) The DHI assesses precipitating physical factors associated with dizziness/unsteadiness and functional/emotional consequences of symptoms. (2) The HADS assesses non-somatic symptoms of anxiety and depression. In addition, patients answered the third question of the University of California Los Angeles-Dizziness Questionnaire which covers the impact of dizziness and unsteadiness on everyday activities. Principal component analysis (PCA) was performed to explore the dimensions of the DHI. Associations were estimated by Spearman correlation coefficients. RESULTS: One hundred ninety-four patients with dizziness or unsteadiness associated with a vestibular disorder, mean age (standard deviation) of 50.6 (13.6) years, participated. Based on eigenvalues greater one respectively the scree plot we analysed diverse factor solutions. The 3-factor solution seems to be reliable, clinically relevant and can partly be explained with the ICF. It explains 49.2% of the variance. Factor 1 comprises the effect of dizziness and unsteadiness on emotion and participation, factor 2 informs about specific activities or effort provoking dizziness and unsteadiness, and factor 3 focuses on self-perceived walking ability in relation to contextual factors. The first factor correlates moderately with disability and the HADS (values >/=0.6). The second factor is comparable with the original physical subscale of the DHI and factors retained in previous studies. CONCLUSIONS: The results of the present survey can not support the original subscale structure of the DHI. Therefore only the total scale should be used. We discuss a possible restructuring of the DHI.

Gamma-linolenic acid supplementation for prophylaxis of atopic dermatitis--a randomized controlled trial in infants at high familial risk.

BACKGROUND: Studies suggest that low concentrations of n-6 long-chain polyenes in early life are correlated to atopic disease in later life. OBJECTIVE: The purpose of the study was to investigate the possible preventive effect of gamma-linolenic acid (GLA) supplementation on the development of atopic dermatitis in infants at risk. DESIGN: In a double-blind, randomized, placebo-controlled trial, formula-fed infants (n = 118) with a maternal history of atopic disease received borage oil supplement (containing 100 mg GLA) or sunflower oil supplement as a placebo daily for the first 6 mo of life. Main outcome measures were the incidence of atopic dermatitis in the first year of life (by UK Working Party criteria), the severity of atopic dermatitis (SCORing Atopic Dermatitis; SCORAD), and the total serum immunoglobulin E (IgE) concentration at the age of 1 y. RESULTS: The intention-to-treat analysis showed a favorable trend for severity of atopic dermatitis associated with GLA supplementation ( x+/- SD SCORAD: 6.32 +/- 5.32) in the GLA-supplemented group as compared with 8.28 +/- 6.54 in the placebo group (P = 0.09; P = 0.06 after adjustment for total serum IgE at baseline, age 1 wk), but no significant effects on the other atopic outcomes. The increase in GLA concentrations in plasma phospholipids between baseline and 3 mo was negatively associated with the severity of atopic dermatitis at 1 y (Spearman's correlation coefficient = -0.233, P = 0.013). There was no significant effect on total serum IgE concentration. CONCLUSION: Early supplementation with GLA in children at high familial risk does not prevent the expression of atopy as reflected by total serum IgE, but it tends to alleviate the severity of atopic dermatitis in later infancy in these children.

A clinical prediction rule for histological chorioamnionitis in preterm newborns.

BACKGROUND: Histological chorioamnionitis (HC) is an intrauterine inflammatory process highly associated with preterm birth and adverse neonatal outcome. HC is often clinically silent and diagnosed postnatally by placental histology. Earlier identification could facilitate treatment individualisation to improve outcome in preterm newborns. AIM: Develop a clinical prediction rule at birth for HC and HC with fetal involvement (HCF) in preterm newborns. METHODS: Clinical data and placental pathology were obtained from singleton preterm newborns (gestational age ≤ 32.0 weeks) born at Erasmus UMC Rotterdam from 2001 to 2003 (derivation cohort; n = 216) or Máxima MC Veldhoven from 2009 to 2010 (validation cohort; n = 206). HC and HCF prediction rules were developed with preference for high sensitivity using clinical variables available at birth. RESULTS: HC and HCF were present in 39% and 24% in the derivation cohort and in 44% and 22% in the validation cohort, respectively. HC was predicted with 87% accuracy, yielding an area under ROC curve of 0.95 (95%CI = 0.92-0.98), a positive predictive value of 80% (95%CI = 74-84%), and a negative predictive value of 93% (95%CI = 88-96%). Corresponding figures for HCF were: accuracy 83%, area under ROC curve 0.92 (95%CI = 0.88-0.96), positive predictive value 59% (95%CI = 52-62%), and negative predictive value 97% (95%CI = 93-99%). External validation expectedly resulted in some loss of test performance, preferentially affecting positive predictive rather than negative predictive values. CONCLUSION: Using a clinical prediction rule composed of clinical variables available at birth, HC and HCF could be predicted with good test characteristics in preterm newborns. Further studies should evaluate the clinical value of these rules to guide early treatment individualisation.

Translation, cross-cultural adaptation and reliability of the german version of the dizziness handicap inventory.

OBJECTIVE: To translate the Dizziness Handicap Inventory into German (DHI-G) and investigate reliability, assess the association between selected items of the University of California Los Angeles Dizziness Questionnaire and the DHI-G, and compare the scores of patients and healthy participants. STUDY DESIGN: Cross-sectional design. SETTING: Tertiary center for vertigo, dizziness, or balance disorders. PATIENTS: One hundred forty-one patients with vertigo, dizziness, and unsteadiness associated with a vestibular disorder, with a mean age (standard deviation) of 51.5 (13.2) years, and 52 healthy individuals participated. INTERVENTIONS: Fourteen patients participated in the cognitive debriefing; 127 patients completed the questionnaires once or twice within 1 week. MAIN OUTCOME MEASURES: The DHI-G assesses disability caused by dizziness and unsteadiness; the items of the University of California Los Angeles Dizziness Questionnaire assess dizziness and impact on everyday activities. Internal consistency was estimated using Cronbach alpha, reproducibility by calculating Bland-Altman limits of agreement and intraclass correlation coefficients. Associations were estimated by Spearman correlation coefficients. RESULTS: Patients filled out the DHI-G without problem and found that their self-perceived disabilities were mostly included. Cronbach alpha values for the DHI-G and the functional, physical, and emotional subscales were 0.90, 0.80, 0.71, and 0.82, respectively. The limits of agreement were +/-12.4 points for the total scale (maximum, 100 points). Intraclass correlation coefficients ranged from 0.90 to 0.95. The DHI-G correlated moderately with the question assessing functional disability (0.56) and fairly with the questions quantifying dizziness (0.43, 0.35). The DHI-G discriminated significantly between healthy participants and patients. CONCLUSION: The DHI-G demonstrated good reliability and is recommended as a measure of disability in patients with dizziness and unsteadiness.

Prescription of benzodiazepines in general practice in the context of a man-made disaster: a longitudinal study.

BACKGROUND: Mental health problems associated with benzodiazepine treatment are often highly prevalent in the aftermath of disasters. Nevertheless, not much is known about benzodiazepine use after disasters. Considering the negative effects associated with prolonged use and the adverse effects of benzodiazepines on recovery of patients with acute stress, the aim of the present study was to explore benzodiazepine use in the context of the Enschede fireworks disaster of 13 May 2000. METHODS: A longitudinal study using electronic medical records of general practitioners. Subjects were patients aged 16 years and older, registered at one of the practices between 1999 and 2003 (1541 victims and 5370 references). Pre- and post-disaster data were available on benzodiazepine prescriptions, healthcare utilization and sociodemographic characteristics. Benzodiazepine use was defined using different criteria (e.g. any use, daily use, chronic use). Data were analysed using multivariate multilevel logistic regression analyses. RESULTS: Compared with patients from a reference group, disaster victims were at increased risk of becoming an incident benzodiazepine user after the disaster. Benzodiazepine use also had a different time course among victims compared with references. However, daily or prolonged use of benzodiazepines was not often observed and did not show dramatic deviations among disaster victims compared with references. CONCLUSION: There is no convincing evidence that general practitioners systematically deviated from clinical guidelines for benzodiazepines, which generally advocate their short time application.