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Influence of timing of maternal antibiotic administration during caesarean section on infant microbial colonisation: a randomised controlled trial.
Dierikx, T, Berkhout, D, Eck, A, Tims, S, van Limbergen, J, Visser, D, de Boer, M, de Boer, N, Touw, D, Benninga, M, et al
Gut. 2022;71(9):1803-1811
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Early-life microbiome acquisition and development can be compromised by external perturbations such as delivery via caesarean section (CS), formula feeding and antibiotics. Currently, based on revised international guidelines, all infants born by CS are exposed to broad-spectrum antibiotics via the umbilical cord. Even though there was not an increase in the incidence of neonatal sepsis, the effects on the gut microbiota colonisation and long-term health consequences remain largely unknown. The hypothesis for this study was that exposure to antibiotics in children delivered by CS, related to the revised international guidelines, influences the microbial colonisation process and may impact health outcome. This study is a randomised controlled trial on the microbiome and health state of infants up to 3 years of age. The study enrolled women delivering via CS who received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20) and women who had a vaginal delivery (n=23). Results show that CS delivery in general leads to a profound impact on the initial microbial colonisation. Furthermore, maternal antibiotic administration prior to CS does not lead to a ‘second hit’ on the already compromised microbiome in CS born infants. Authors conclude that early-life microbiome development is strongly affected by mode of delivery.
Abstract
OBJECTIVE Revised guidelines for caesarean section (CS) advise maternal antibiotic administration prior to skin incision instead of after umbilical cord clamping, unintentionally exposing the infant to antibiotics antenatally. We aimed to investigate if timing of intrapartum antibiotics contributes to the impairment of microbiota colonisation in CS born infants. DESIGN In this randomised controlled trial, women delivering via CS received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20). A third control group of vaginally delivering women (n=23) was included. Faecal microbiota was determined from all infants at 1, 7 and 28 days after birth and at 3 years by 16S rRNA gene sequencing and whole-metagenome shotgun sequencing. RESULTS Compared with vaginally born infants, profound differences were found in microbial diversity and composition in both CS groups in the first month of life. A decreased abundance in species belonging to the genera Bacteroides and Bifidobacterium was found with a concurrent increase in members belonging to the phylum Proteobacteria. These differences could not be observed at 3 years of age. No statistically significant differences were observed in taxonomic and functional composition of the microbiome between both CS groups at any of the time points. CONCLUSION We confirmed that microbiome colonisation is strongly affected by CS delivery. Our findings suggest that maternal antibiotic administration prior to CS does not result in a second hit on the compromised microbiome. Future, larger studies should confirm that antenatal antibiotic exposure in CS born infants does not aggravate colonisation impairment and impact long-term health.
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Effects of Fecal Microbiome Transfer in Adolescents With Obesity: The Gut Bugs Randomized Controlled Trial.
Leong, KSW, Jayasinghe, TN, Wilson, BC, Derraik, JGB, Albert, BB, Chiavaroli, V, Svirskis, DM, Beck, KL, Conlon, CA, Jiang, Y, et al
JAMA network open. 2020;3(12):e2030415
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Obesity has become a global pandemic even in adolescents. Lifestyle interventions have had limited impact on this cohort and drugs targeting obesity are often unlicensed in children. The gut microbiome has a role in weight regulation and may be a new target in adolescents with obesity. This randomised control trial of 87 adolescents with obesity over 26 weeks, aimed to assess if faecal microbiome transfer (FMT), which is a method whereby faecal matter is transplanted from one person to another, can be used to treat obesity. The results showed that FMT did not have an effect on body mass index (BMI) and the intervention group had a marginally increased BMI after FMT. Other disorders associated with obesity such as blood sugar levels were also unaffected by FMT, however there was a reduction in fat storage around the middle. It was concluded that FMT alone is not adequate to improve obesity in adolescents, but may reduce fat stored around the middle. Healthcare professionals could use this study to understand that simply transplanting one person’s gut microbiome to another, may not be enough. Targeted personalised approaches may be required, however further research is needed.
Abstract
Importance: Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation. Objective: To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism. Design, Setting, and Participants: This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020. Interventions: Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo. Main Outcomes and Measures: Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition. Results: Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007). There were no serious adverse events recorded throughout the trial. Conclusions and Relevance: In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615001351505.
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The Association of Body Mass Index and Body Composition with Pain, Disease Activity, Fatigue, Sleep and Anxiety in Women with Fibromyalgia.
Correa-Rodríguez, M, Mansouri-Yachou, JE, Casas-Barragán, A, Molina, F, Rueda-Medina, B, Aguilar-Ferrandiz, ME
Nutrients. 2019;11(5)
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Fibromyalgia is a long-term condition causing symptoms such as widespread pain, fatigue, trouble sleeping and problems with memory and concentration. The purpose of this study was to examine the relationships between body mass index (BMI), body composition and fibromyalgia symptoms. 73 women with fibromyalgia and 73 healthy controls, matched on weight, were included in this cross-sectional study. Women with a higher BMI had more severe symptoms of fibromyalgia. Fat mass and visceral fat were associated with poorer quality sleep. The study’s authors concluded that promoting an ideal BMI may help to reduce some of the symptoms for women with fibromyalgia.
Abstract
The link between fibromyalgia syndrome (FMS) and obesity has not been thoroughly investigated. The purpose of this study was to examine the relationships among body mass index (BMI) and body composition parameters, including fat mass, fat mass percentage, and visceral fat, as well as FMS features, such as tender point count (TPC), pain, disease activity, fatigue, sleep quality, and anxiety, in a population of FMS women and healthy controls. A total of seventy-three women with FMS and seventy-three healthy controls, matched on weight, were included in this cross-sectional study. We used a body composition analyzer to measure fat mass, fat mass percentage, and visceral fat. Tender point count (TPC) was measured by algometry pressure. The disease severity was measured with the Fibromyalgia Impact Questionnaire (FIQ-R) and self-reported global pain was evaluated with the visual analog scale (VAS). To measure the quality of sleep, fatigue, and anxiety we used the Pittsburgh Sleep Quality Questionnaire (PSQI), the Spanish version of the multidimensional fatigue inventory (MFI), and the Beck Anxiety Inventory (BAI), respectively. Of the women in this study, 38.4% and 31.5% were overweight and obese, respectively. Significant differences in FIQ-R.1 (16.82 ± 6.86 vs. 20.66 ± 4.71, p = 0.030), FIQ-R.3 (35.20 ± 89.02 vs. 40.33 ± 5.60, p = 0.033), and FIQ-R total score (63.87 ± 19.12 vs. 75.94 ± 12.25, p = 0.017) among normal-weight and overweight FMS were observed. Linear analysis regression revealed significant associations between FIQ-R.2 (β(95% CI)= 0.336, (0.027, 0.645), p = 0.034), FIQ-R.3 (β(95% CI)= 0.235, (0.017, 0.453), p = 0.035), and FIQ-R total score (β(95% CI)= 0.110, (0.010, 0.209), p = 0.032) and BMI in FMS women after adjusting for age and menopause status. Associations between sleep latency and fat mass percentage in FMS women (β(95% CI)= 1.910, (0.078, 3.742), p = 0.041) and sleep quality and visceral fat in healthy women (β(95% CI)= 2.614, (2.192, 3.036), p = 0.008) adjusted for covariates were also reported. The higher BMI values are associated with poor FIQ-R scores and overweight and obese women with FMS have higher symptom severity. The promotion of an optimal BMI might contribute to ameliorate some of the FMS symptoms.
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Examining Weight Bias among Practicing Canadian Family Physicians.
Alberga, AS, Nutter, S, MacInnis, C, Ellard, JH, Russell-Mayhew, S
Obesity facts. 2019;12(6):632-638
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Weight bias represents negative attitudes and beliefs about individuals because of their weight. The aim of this study was to examine: a. weight bias in a national sample of family physicians in Canada, b. the relationships between weight bias, attitudes about treating patients with obesity, and how people with obesity are perceived as a burden to the public healthcare system. A probability sample of 400 currently practicing family physicians completed the survey by phone or online. Results show that most respondents were white (63.3%) men (61.3%) aged 45 years or older. The average total score of explicit weight bias was 2.95 (1.17) evaluated on a 7-point Likert scale. Furthermore, although weight bias was not present in the majority of the sample, it was present among some physicians. Authors conclude that future work is needed to investigate weight bias reduction techniques targeted at physicians.
Abstract
OBJECTIVES The aim of this study was to examine the attitudes of practicing Canadian family physicians about individuals with obesity, their healthcare treatment, and perceptions of obesity treatment in the public healthcare system. METHOD A national sample of Canadian practicing family physicians (n = 400) completed the survey. Participants completed measures of explicit weight bias, attitudes towards treating patients with obesity, and perceptions that people with obesity increase demand on the public healthcare system. RESULTS Responses consistent with weight bias were not observed overall but were demonstrated in a sizeable minority of respondents. Many physicians also reported feeling frustrated with patients with obesity and agreed that people with obesity increase demand on the public healthcare system. Male physicians had more negative attitudes than females. More negative attitudes towards treating patients with obesity were associated with greater perceptions of them as a public health demand. CONCLUSION Results suggest that negative attitudes towards patients with obesity exist among some family physicians in Canada. It remains to be determined if physicians develop weight bias partly because they blame individuals for their obesity and its increased demand on the Canadian public healthcare system. More research is needed to better understand causes and consequences of weight bias among health professionals and make efforts towards its reduction in healthcare.
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Is waist-to-height ratio the best predictive indicator of hypertension incidence? A cohort study.
Rezende, AC, Souza, LG, Jardim, TV, Perillo, NB, Araújo, YCL, de Souza, SG, Sousa, ALL, Moreira, HG, de Souza, WKSB, do Rosário Gondim Peixoto, M, et al
BMC public health. 2018;18(1):281
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A variety of methods of measuring body fat are used as tools to predict the risk of developing certain lifestyle-related diseases such as high blood pressure. It is not yet clear which of these methods is the most accurate. The aim of this study was to evaluate and compare the effectiveness of using different measures of body fat to predict high blood pressure. The study was performed in Brazil. Adult volunteers with normal blood pressure were assessed for body fat using waist-to-height ratio (WHtR), body mass index (BMI) and waist circumference (WC), and then followed-up 13 years later to find out whether they had developed high blood pressure. 44% of the participants developed high blood pressure during the study period. BMI, WC and WHtR were all associated with the risk of high blood pressure and had similar accuracy in predicting the disease. However, the associations were only significant for women. The cut-off points for predicting high blood pressure agreed with current recommendations, except for the WC in men. The results suggest that both overall obesity (BMI) and central obesity (WC and WHtR) indicators can be used in this population to evaluate the risk of developing high blood pressure.
Abstract
BACKGROUND The best anthropometric indicator to verify the association between obesity and hypertension (HTN) has not been established. We conducted this study to evaluate and compare the discriminatory power of waist-to-height ratio (WHtR) in relation to body mass index (BMI) and waist circumference (WC) in predicting HTN after 13 years of follow-up. METHODS This study was an observational prospective cohort study performed in the city of Firminópolis, in Brazilian's midwest. The cohort baseline (phase 1) was initiated in 2002 with the evaluation of a representative sample of the normotensive population (≥ 18 years of age). The incidence of HTN was evaluated as the outcome (phase 2). Sociodemographic, dietary and lifestyle variables were used to adjust proportional hazards models and evaluate risk of HTN according to anthropometric indices. The areas under the receiver operating characteristic (ROC) curves were used to compare the predictive capacity of these indices. The best HTN predictor cut-offs were obtained based on sensitivity and specificity. RESULTS A total of 471 patients with a mean age of 38.9 ± 12.3 years were included in phase 1. The mean follow-up was 13.2 years, and 207 subjects developed HTN. BMI, WC and WHtR were associated with risk of HTN incidence and had similar power in predicting the disease. However, the associations were only significant for women. The cut-off points with a better HTN predictive capacity were in agreement with current recommendations, except for the WC in men. CONCLUSIONS The results suggest that both overall obesity (BMI) and central obesity (WC and WHtR) anthropometric indicators can be used in this population to evaluate the risk of developing hypertension.
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Fasting glucose and body mass index as predictors of activity in breast cancer patients treated with everolimus-exemestane: The EverExt study.
Pizzuti, L, Marchetti, P, Natoli, C, Gamucci, T, Santini, D, Scinto, AF, Iezzi, L, Mentuccia, L, D'Onofrio, L, Botticelli, A, et al
Scientific reports. 2017;7(1):10597
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Literature shows that hyperglycaemia is amongst the most common grade 3 or 4 drug-related adverse events in breast cancer patients. The aim of the study was to investigate the role of anthropometrics and biomarkers of glucose metabolism on treatment outcomes in advanced breast cancer patients. The study is an observational study that recruited 102 postmenopausal women, aged at least 18 years, who were diagnosed with advanced breast cancer and treated with everolimus and exemestane. Results indicate a significant trend towards increasing fasting glucose and decreasing BMI in the overall study population. Furthermore, significant evidence also shows that lower levels of fasting glucose is associated with better outcomes. Authors conclude that their study showed a predictive role of fasting glucose and BMI on treatment outcomes, longer progression free survival and clinical benefit rates (percentage of patients with shrinking tumours or stable disease for at least 6 months).
Abstract
Evidence on everolimus in breast cancer has placed hyperglycemia among the most common high grade adverse events. Anthropometrics and biomarkers of glucose metabolism were investigated in a observational study of 102 postmenopausal, HR + HER2- metastatic breast cancer patients treated with everolimus-exemestane in first and subsequent lines. Best overall response (BR) and clinical benefit rate (CBR) were assessed across subgroups defined upon fasting glucose (FG) and body mass index (BMI). Survival was estimated by Kaplan-Meier method and log-rank test. Survival predictors were tested in Cox models. Median follow up was 12.4 months (1.0-41.0). The overall cohort showed increasing levels of FG and decreasing BMI (p < 0.001). Lower FG fasting glucose at BR was more commonly associated with C/PR or SD compared with PD (p < 0.001). We also observed a somewhat higher BMI associated with better response (p = 0.052). More patients in the lowest FG category achieved clinical benefit compared to the highest (p < 0.001), while no relevant differences emerged for BMI. Fasting glucose at re-assessment was also predictive of PFS (p = 0.037), as confirmed in models including BMI and line of therapy (p = 0.049). Treatment discontinuation was significantly associated with changes in FG (p = 0.014). Further research is warranted to corroborate these findings and clarify the underlying mechanisms.
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Randomized placebo control study of insulin sensitizers (Metformin and Pioglitazone) in psoriasis patients with metabolic syndrome (Topical Treatment Cohort).
Singh, S, Bhansali, A
BMC dermatology. 2016;16(1):12
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As an immune-mediated chronic inflammatory skin condition, psoriasis is associated with obesity, metabolic syndrome, diabetes, and cardiovascular disease. Medications capable of sensitising insulin, such as Metformin and Pioglitazone, have also shown benefits in improving factors associated with metabolic syndrome and psoriasis. This single-centre, parallel-group, randomised, open-label with blinded endpoint evaluated the effects of Metformin with Pioglitazone and placebo in psoriatic patients. Patients with mild-to-moderate psoriasis were randomised to a topical treatment cohort to take 1000 mg metformin daily or 30 mg pioglitazone or placebo groups for 12 weeks. Each participant received a topical ointment containing 5% coal tar during the treatment period. The Metformin and Pioglitazone groups showed significant improvements in psoriasis and metabolic syndrome parameters, such as fasting plasma glucose, total cholesterol, and triglyceride levels, after 12 weeks of treatment. The treatment with metformin resulted in significant improvements in weight, BMI, waist circumference, FPG, triglycerides, and total cholesterol, while the treatment with pioglitazone resulted in significant improvements in FPG, triglycerides, systolic and diastolic blood pressure, cholesterol levels, and LDL cholesterol levels. There was no significant improvement in inflammatory cytokine levels in any group. For further evaluation of the beneficial effects of insulin-sensitising drugs in patients suffering from psoriasis and metabolic syndrome, more robust studies are needed. The study results can be used by healthcare professionals to better understand how insulin-sensitising drugs may decrease the risk of diabetes, cardiovascular disease, and psoriasis in psoriasis patients with metabolic syndrome.
Abstract
BACKGROUND Increased prevalence of metabolic syndrome (MS) is observed in psoriasis. Metformin has shown improvement in cardiovascular risk factors while pioglitazone demonstrated anti proliferative, anti-inflammatory and anti angiogenic effects. Study objective is to evaluate the efficacy and safety of Insulin sensitizers (metformin and pioglitazone) in psoriasis patients with metabolic syndrome (MS). METHODS Single centre, parallel group, randomized, study of metformin, pioglitazone and placebo in psoriasis patients with MS. RESULTS Statistically significant improvement was observed in Psoriasis Area and Severity Index (PASI), Erythema, Scaling and Induration (ESI) and Physician global assessment (PGA) scores in pioglitazone (p values - PASI = 0.001, ESI = 0.002, PGA = 0.008) and metformin groups (p values - PASI = 0.001, ESI = 0.016, PGA = 0.012) as compared to placebo. There was statistically significant difference in percentage of patients achieving 75 % reduction in PASI and ESI scores in metformin (p value - PASI = 0.001, ESI = 0.001) and pioglitazone groups (p vaue - PASI = 0.001, ESI = 0.001). Significant improvement was observed in fasting plasma glucose (FPG) and triglycerides levels in metformin and pioglitazone arms. Significant improvement was noted in weight, BMI, waist circumference, FPG, triglycerides and total cholesterol after 12 weeks of treatment with metformin while pioglitazone showed improvement in FPG, triglyceride levels, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol and LDL cholesterol levels. There was no difference in pattern of adverse drug reaction in three groups. CONCLUSION Insulin sensitizers have shown improvement in the parameters of MS as well as disease severity in psoriasis patients. TRIAL REGISTRATION CTRI Registration Number: CTRI/2011/12/002252 . Registered on 19/12/2011.