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A randomized controlled trial of an oral probiotic to reduce antepartum group B Streptococcus colonization and gastrointestinal symptoms.
Hanson, L, VandeVusse, L, Forgie, M, Malloy, E, Singh, M, Scherer, M, Kleber, D, Dixon, J, Hryckowian, AJ, Safdar, N
American journal of obstetrics & gynecology MFM. 2023;5(1):100748
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Plain language summary
Streptococcus agalactiae (or group B Streptococcus [GBS]) is an encapsulated, gram-positive, beta-haemolytic anaerobe that asymptomatically colonizes the genitourinary tract. Vertical transmission of GBS during normal vaginal birth can lead to neonatal colonization and risk for early-onset GBS disease. The aim of this study was to present the findings of a phase II, double-blind, randomised, placebo-controlled trial of an antenatal probiotic intervention to reduce GBS colonization. A secondary aim was to determine if the probiotic intervention reduces gastrointestinal (GI) symptoms of pregnancy. Participants (n=107) were randomly assigned to one of the two groups: probiotic intervention (n=55) or placebo group (n=54). Results show that: - there weren’t any significant differences between the groups in demographic characteristics, perinatal or neonatal outcomes, or intrapartum antibiotic prophylaxis doses. - there wasn’t any significant difference between groups in the presence of the probiotic bacteria on the rectal swabs, whereas the vaginal swabs showed a trend toward greater presence in probiotic group participants. - more probiotic participants took antenatal antibiotics (5/39) compared with controls (1/44). Authors conclude that probiotic bacteria colonisation of the genitourinary tract occurred more in the intervention group than in the control group and significantly reduced GI symptoms of pregnancy.
Abstract
BACKGROUND Probiotics have been suggested as a strategy to reduce antenatal group B Streptococcus colonization. Although probiotics are known to improve gastrointestinal symptoms, this has not been studied during pregnancy. OBJECTIVE This study aimed to evaluate the efficacy of a probiotic to reduce: (1) standard-of-care antenatal group B Streptococcus colonization and colony counts and (2) gastrointestinal symptoms of pregnancy. STUDY DESIGN In a double-blind fashion, 109 healthy adult pregnant people were randomized to Florajen3 probiotic or placebo capsules once daily from 28 weeks' gestation until labor onset. Baseline vaginal and rectal study swabs for group B Streptococcus colony-forming units and microbiome analysis were collected at 28 and 36 weeks' gestation. Standard-of-care vaginal to rectal group B Streptococcus swabs were collected from all participants at 36 weeks' gestation and determined the need for intrapartum antibiotic prophylaxis. Data collection included solicitation of adverse events, demographic information, Antepartum Gastrointestinal Symptom Assessment score, yogurt ingestion, sexual activity, and vaginal cleaning practices. RESULTS A total of 83 participants completed the study to 36 weeks' gestation with no adverse events. Standard-of-care group B Streptococcus colonization was 20.4% in the control group and 15.4% in probiotic group participants (-5%; P=.73). The relative risk for positive standard-of-care vaginal-rectal group B Streptococcus colonization was 1.33 (95% confidence interval, 0.5-3.40) times higher in the control group than in the probiotic group (P=.55). There were no differences in median vaginal (P=.16) or rectal (P=.20) group B streptococcus colony-forming units at baseline or at 36 weeks (vaginal P>.999; rectal P=.56). Antepartum Gastrointestinal Symptom Assessment scores were similar at baseline (P=.19), but significantly decreased in probiotic group participants at 36 weeks (P=.02). No covariates significantly altered group B Streptococcus colonization. Significantly more Florajen3 bacteria components were recovered from the vaginal-rectal samples of probiotic group participants (32%; P=.04) compared with controls. CONCLUSION The findings of this study provided insufficient evidence for the clinical application of the Florajen3 probiotic intervention to reduce standard-of-care vaginal-rectal group B Streptococcus colonization. The prevalence of group B Streptococcus was lower than expected in the study population, and intervention adherence was poor. Probiotic bacteria colonization of the genitourinary tract occurred more in intervention group participants than in controls and significantly reduced gastrointestinal symptoms of pregnancy.
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Semi-solid MT and APTw CEST-MRI predict clinical outcome of patients with glioma early after radiotherapy.
Kroh, F, von Knebel Doeberitz, N, Breitling, J, Maksimovic, S, König, L, Adeberg, S, Scherer, M, Unterberg, A, Bendszus, M, Wick, W, et al
Magnetic resonance in medicine. 2023;(4):1569-1581
Abstract
PURPOSE The purpose of this study was to compare the potential of asymmetry-based (APTwasym ), Lorentzian-fit-based (PeakAreaAPT and MTconst ), and relaxation-compensated (MTRRex APT and MTRRex MT) CEST contrasts of the amide proton transfer (APT) and semi-solid magnetization transfer (ssMT) for early response assessment and prediction of progression-free survival (PFS) in patients with glioma. METHODS Seventy-two study participants underwent CEST-MRI at 3T from July 2018 to December 2021 in a prospective clinical trial four to 6 wk after the completion of radiotherapy for diffuse glioma. Tumor segmentations were performed on T2w -FLAIR and contrast-enhanced T1w images. Therapy response assessment and determination of PFS were performed according to response assessment in neuro oncology (RANO) criteria using clinical follow-up data with a median observation time of 9.2 mo (range, 1.6-40.8) and compared to CEST MRI metrics. Statistical testing included receiver operating characteristic analyses, Mann-Whitney-U-test, Kaplan-Meier analyses, and logrank-test. RESULTS MTconst (AUC = 0.79, p < 0.01) showed a stronger association with RANO response assessment compared to PeakAreaAPT (AUC = 0.71, p = 0.02) and MTRRex MT (AUC = 0.71, p = 0.02), and enabled differentiation of participants with pseudoprogression (n = 8) from those with true progression (AUC = 0.79, p = 0.02). Furthermore, MTconst (HR = 3.04, p = 0.01), PeakAreaAPT (HR = 0.39, p = 0.03), and APTwasym (HR = 2.63, p = 0.02) were associated with PFS. MTRRex APT was not associated with any outcome. CONCLUSION MTconst , PeakAreaAPT, and APTwasym imaging predict clinical outcome by means of progression-free survival. Furthermore, MTconst enables differentiation of radiation-induced pseudoprogression from disease progression. Therefore, the assessed metrics may have synergistic potential for supporting clinical decision making during follow-up of patients with glioma.
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Author Correction: Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.
de Rojas, I, Moreno-Grau, S, Tesi, N, Grenier-Boley, B, Andrade, V, Jansen, IE, Pedersen, NL, Stringa, N, Zettergren, A, Hernández, I, et al
Nature communications. 2023;(1):716
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Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning.
Lahti, J, Tuominen, S, Yang, Q, Pergola, G, Ahmad, S, Amin, N, Armstrong, NJ, Beiser, A, Bey, K, Bis, JC, et al
Molecular psychiatry. 2022;(11):4419-4431
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Abstract
Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.
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Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.
de Rojas, I, Moreno-Grau, S, Tesi, N, Grenier-Boley, B, Andrade, V, Jansen, IE, Pedersen, NL, Stringa, N, Zettergren, A, Hernández, I, et al
Nature communications. 2021;(1):3417
Abstract
Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.
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Episodes of care in a primary care walk-in clinic at a refugee camp in Germany - a retrospective data analysis.
Oltrogge, JH, Schäfer, I, Schlichting, D, Jahnke, M, Rakebrandt, A, Pruskil, S, Wagner, HO, Lühmann, D, Scherer, M
BMC family practice. 2020;(1):193
Abstract
BACKGROUND From 2015 to 2016 Germany faced an influx of 1.16 million asylum seekers. In the state of Hamburg Primary Care walk-in clinics (PCWC) were commissioned at refugee camps because the high number of residents (57,000 individuals) could not be provided with access to regular healthcare services. Our study aims were (1) to describe the utilization of a PCWC by camp residents, (2) to compare episodes of continuous care with shorter care episodes and (3) to analyse which diagnoses predict episodes of continuous care in this setting. METHODS A retrospective longitudinal observational study was conducted by reviewing all anonymized electronic medical records of a PCWC that operated from 4th November 2015 to 22nd July 2016 at a refugee camp in Hamburg. Episodes of care (EOC) were extracted based on the international classification of primary care-2nd edition (ICPC-2). Outcome parameters were episode duration, principal diagnoses, and medical procedures. RESULTS We analysed 5547 consultations of 1467 patients and extracted 4006 EOC. Mean patient age was 22.7 ± 14.8 years, 37.3% were female. Most common diagnoses were infections (44.7%), non-communicable diseases (22.2%), non-definitive diagnoses describing symptoms (22.0%), and injuries (5.7%). Most patients (52.4%) had only single encounters, whereas 19.8% had at least one EOC with a duration of ≥ 28 days (defined as continuous care). Several procedures were more prevalent in EOC with continuous care: Blood tests (5.2 times higher), administrative procedures (4.3), imaging (3.1) and referrals to secondary care providers (3.0). Twenty prevalent ICPC-2-diagnosis groups were associated with continuous care. The strongest associations were endocrine/metabolic system and nutritional disorders (hazard ratio 5.538, p < 0.001), dermatitis/atopic eczema (4.279, p < 0.001) and psychological disorders (4.056, p < 0.001). CONCLUSION A wide spectrum of acute and chronic health conditions could be treated at a GP-led PCWC with few referrals or use of medical resources. But we also observed episodes of continuous care with more use of medical resources and referrals. Therefore, we conclude that principles of primary care like continuity of care, coordination of care and management of symptomatic complaints could complement future healthcare concepts for refugee camps.
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The Perioperative Care of Older Patients.
Olotu, C, Weimann, A, Bahrs, C, Schwenk, W, Scherer, M, Kiefmann, R
Deutsches Arzteblatt international. 2019;(5):63-69
Abstract
BACKGROUND Elderly patients are a growing and vulnerable group with an elevated perioperative risk. Perioperative treatment pathways that take these patients' special risks and requirements into account are often not implemented in routine clinical practice. METHODS This review is based on pertinent publications retrieved by a selective search in PubMed, the AWMF guideline database, and the Cochrane database for guidelines from Germany and abroad, meta-analyses, and Cochrane reviews. RESULTS The care of elderly patients who need surgery calls for an interdisciplinary, interprofessional treatment concept. One component of this concept is preoperative preparation of the patient ("prehabilitation"), which is best initiated before hospital admission, e.g., correction of deficiency states, optimization of chronic drug treatment, and respiratory training. Another important component consists of pre-, intra-, and postoperative measures to prevent delirium, which can lower the frequency of this complication by 30-50%: these include orientation aids, avoidance of inappropriate drugs for elderly patients, adequate analgesia, early mobilization, short fasting times, and a perioperative nutrition plan. Preexisting cognitive impairment predisposes to postoperative delirium (odds ratios [OR] ranging from 2.5 to 4.5). Frailty is the most important predictor of the postoperative course (OR: 2.6-11). It follows that preoperative assessment of the patient's functional and cognitive status is essential. CONCLUZION The evidence-based and guideline-consistent care of elderly patients requires not only close interdisciplinary, interprofessional, and cross-sectoral collaboration, but also the restructuring and optimization of habitual procedural pathways in the hospital. Elderly patients' special needs can only be met by a treatment concept in which the entire perioperative phase is considered as a single, coherent process.
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Health-promoting factors in the freshman year of medical school: a longitudinal study.
Kötter, T, Tautphäus, Y, Obst, KU, Voltmer, E, Scherer, M
Medical education. 2016;(6):646-56
Abstract
CONTEXT The freshman year of medical school is a stressful period in the lives of future doctors. Resilience to this stress differs greatly, leading to different health outcomes. Less resilient students, whose health may deteriorate early in their education, are at greater risk for developing stress-related diseases. Early identification of individuals at risk and the provision of tailored health-promoting interventions might prevent this. OBJECTIVES This study was designed to investigate: (i) how the health of medical students develops over the freshman year, and (ii) whether certain protective factors can predict general and mental health status after 1 year of medical education. METHODS A prospective, longitudinal, observational study was conducted at one medical school. Self-rated general and mental health status before and after the freshman year were used as outcomes. In addition to socio-demographic variables and leisure activities, personality and study-related behaviour and experience were surveyed as potential predictors. Both descriptive techniques and logistic regression analyses were employed to identify predictors for general and mental health separately. RESULTS At baseline, 93% of medical students rated their general health and 88% rated their mental health as good. These frequencies declined over the first year to 76% and 84%, respectively. For general health, regular physical activity was the strongest predictor (odds ratio [OR] 4.58). Satisfaction with life (OR 1.18) and balance and mental stability (OR 1.20) emerged as positive predictors, and age (OR 0.85) and striving for perfection (OR 0.76) as negative predictors. Mental health status was predicted by emotional distancing (OR 1.25), experience of social support (OR 0.73), neuroticism (OR 0.89) and age (OR 0.85). CONCLUSIONS Self-rated general and mental health declined throughout the first year of medical education. Physical activity proved to be a strong predictor for the maintenance of good general health. This finding may represent a starting point for health-promoting interventions, such as the provision of time slots for physical activity.
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Specific dietary preferences are linked to differing gut microbial metabolic activity in response to dark chocolate intake.
Martin, FP, Montoliu, I, Nagy, K, Moco, S, Collino, S, Guy, P, Redeuil, K, Scherer, M, Rezzi, S, Kochhar, S
Journal of proteome research. 2012;(12):6252-63
Abstract
Systems biology approaches are providing novel insights into the role of nutrition for the management of health and disease. In the present study, we investigated if dietary preference for dark chocolate in healthy subjects may lead to different metabolic response to daily chocolate consumption. Using NMR- and MS-based metabolic profiling of blood plasma and urine, we monitored the metabolic response of 10 participants stratified as chocolate desiring and eating regularly dark chocolate (CD) and 10 participants stratified as chocolate indifferent and eating rarely dark chocolate (CI) to a daily consumption of 50 g of dark chocolate as part of a standardized diet over a one week period. We demonstrated that preference for chocolate leads to different metabolic response to chocolate consumption. Daily intake of dark chocolate significantly increased HDL cholesterol by 6% and decreased polyunsaturated acyl ether phospholipids. Dark chocolate intake could also induce an improvement in the metabolism of long chain fatty acid, as noted by a compositional change in plasma fatty acyl carnitines. Moreover, a relationship between regular long-term dietary exposure to a small amount of dark chocolate, gut microbiota, and phenolics was highlighted, providing novel insights into biological processes associated with cocoa bioactives.
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Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial.
Budoff, MJ, Dowe, D, Jollis, JG, Gitter, M, Sutherland, J, Halamert, E, Scherer, M, Bellinger, R, Martin, A, Benton, R, et al
Journal of the American College of Cardiology. 2008;(21):1724-32
Abstract
OBJECTIVES The purpose of this study was to evaluate the diagnostic accuracy of electrocardiographically gated 64-multidetector row coronary computed tomographic angiography (CCTA) in individuals without known coronary artery disease (CAD). BACKGROUND CCTA is a promising method for detection and exclusion of obstructive coronary artery stenosis. To date, no prospective multicenter trial has evaluated the diagnostic accuracy of 64-multidetector row CCTA in populations with intermediate prevalence of CAD. METHODS We prospectively evaluated subjects with chest pain at 16 sites who were clinically referred for invasive coronary angiography (ICA). CCTAs were scored by consensus of 3 independent blinded readers. The ICAs were evaluated for coronary stenosis based on quantitative coronary angiography (QCA). No subjects were excluded for baseline coronary artery calcium score or body mass index. RESULTS A total of 230 subjects underwent both CCTA and ICA (59.1% male; mean age: 57 +/- 10 years). On a patient-based model, the sensitivity, specificity, and positive and negative predictive values to detect > or =50% or > or =70% stenosis were 95%, 83%, 64%, and 99%, respectively, and 94%, 83%, 48%, 99%, respectively. No differences in sensitivity and specificity were noted for nonobese compared with obese subjects or for heart rates < or =65 beats/min compared with >65 beats/min, whereas calcium scores >400 reduced specificity significantly. CONCLUSIONS In this prospective multicenter trial of chest pain patients without known CAD, 64-multidetector row CCTA possesses high diagnostic accuracy for detection of obstructive coronary stenosis at both thresholds of 50% and 70% stenosis. Importantly, the 99% negative predictive value at the patient and vessel level establishes CCTA as an effective noninvasive alternative to ICA to rule out obstructive coronary artery stenosis. (A Study of Computed Tomography [CT] for Evaluation of Coronary Artery Blockages in Typical or Atypical Chest Pain; NCT00348569).