Effects of Synbiotics on the Fecal Microbiome and Metabolomic Profiles of Healthy Research Dogs Administered Antibiotics: A Randomized, Controlled Trial

Background: Antibiotic-associated gastrointestinal signs occurred in 100% of dogs administered enrofloxacin with metronidazole in a previous study, and signs partially were mitigated by synbiotics. The objective of this randomized, double-blinded, placebo-controlled trial was to compare the fecal microbiome and metabolome of dogs administered enrofloxacin and metronidazole, followed by either a placebo or a bacterial/yeast synbiotic combination.Methods: Twenty-two healthy research dogs were randomized to two treatment groups. There were three study periods: baseline, treatment, and washout. Dogs were administered enrofloxacin (10 mg/kg qd) and metronidazole (12.5 mg/kg BID), followed 1 h later by placebo or a commercially-available synbiotic combination (BID), per os for 21 days with reevaluation 56 days thereafter. Fecal samples were collected on days 5–7 (baseline), 26–28, and 82–84. The fecal microbiome was analyzed by qPCR and sequencing of 16S rRNA genes; time-of-flight mass spectrometry was used to determine metabolomic profiles. Split plot repeated measures mixed model ANOVA was used to compare results between treatment groups. P < 0.05 was considered significant, with Benjamini and Hochberg's False Discovery Rate used to adjust for multiple comparisons.Results: Alpha diversity metrics differed significantly over time in both treatment groups, with incomplete recovery by days 82–84. Beta diversity and the dysbiosis index differed significantly over time and between treatment groups, with incomplete recovery at days 82–84 for dogs in the placebo group. Significant group-by-time interactions were noted for 15 genera, including Adlercreutzia, Bifidobacterium, Slackia, Turicibacter, Clostridium (including C. hiranonis) [Ruminococcus], Erysipelotrichaceae_g_, [Eubacterium], and Succinivibrionaceae_g_. Concurrent group and time effects were present for six genera, including Collinsella, Ruminococcaceae_g_, and Prevotella. Metabolite profiles differed significantly by group-by-time, group, and time for 28, 20, and 192 metabolites, respectively. These included short-chain fatty acid, bile acid, tryptophan, sphingolipid, benzoic acid, and cinnaminic acid metabolites, as well as fucose and ethanolamine. Changes in many taxa and metabolites persisted through days 82–84.Conclusion: Antibiotic administration causes sustained dysbiosis and dysmetabolism in dogs. Significant group-by-time interactions were noted for a number of taxa and metabolites, potentially contributing to decreased antibiotic-induced gastrointestinal effects in dogs administered synbiotics.

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Short and long-term effects of a synbiotic on clinical signs, the fecal microbiome, and metabolomic profiles in healthy research cats receiving clindamycin: a randomized, controlled trial

PeerJ ◽

10.7717/peerj.5130 ◽

2018 ◽

Vol 6 ◽

pp. e5130 ◽

Cited By ~ 5

Author(s):

Jacqueline C. Whittemore ◽

Jennifer E. Stokes ◽

Nicole L. Laia ◽

Joshua M. Price ◽

Jan S. Suchodolski

Keyword(s):

Randomized Controlled Trial ◽

Controlled Trial ◽

Clinical Signs ◽

16S Rrna Genes ◽

Rrna Genes ◽

Fecal Microbiome ◽

Treatment Groups ◽

Randomized Controlled ◽

Short And Long Term

Background Antibiotic-associated gastrointestinal signs (AAGS) occur commonly in cats. Co-administration of synbiotics is associated with decreased AAGS in people, potentially due to stabilization of the fecal microbiome and metabolome. The purpose of this double-blinded randomized-controlled trial was to compare AAGS and the fecal microbiome and metabolome between healthy cats that received clindamycin with a placebo or synbiotic. Methods 16 healthy domestic shorthair cats from a research colony were randomized to receive 150 mg clindamycin with either a placebo (eight cats) or commercially-available synbiotic (eight cats) once daily for 21 days with reevaluation 603 days thereafter. All cats ate the same diet. Food consumption, vomiting, and fecal score were recorded. Fecal samples were collected daily on the last three days of baseline (days 5–7), treatment (26–28), and recovery (631–633). Sequencing of 16S rRNA genes and gas chromatography time-of-flight mass spectrometry was performed. Clinical signs, alpha and beta diversity metrics, dysbiosis indices, proportions of bacteria groups, and metabolite profiles were compared between treatment groups using repeated measures ANOVAs. Fecal metabolite pathway analysis was performed. P < 0.05 was considered significant. The Benjamini & Hochberg’s False Discovery Rate was used to adjust for multiple comparisons. Results Median age was six and five years, respectively, for cats in the placebo and synbiotic groups. Hyporexia, vomiting, diarrhea, or some combination therein were induced in all cats. Though vomiting was less in cats receiving a synbiotic, the difference was not statistically significant. Bacterial diversity decreased significantly on days 26–28 in both treatment groups. Decreases in Actinobacteria (Bifidobacterium, Collinsella, Slackia), Bacteriodetes (Bacteroides), Lachnospiraceae (Blautia, Coprococcus, Roseburia), Ruminococcaceae (Faecilobacterium, Ruminococcus), and Erysipelotrichaceae (Bulleidia, [Eubacterium]) and increases in Clostridiaceae (Clostridium) and Proteobacteria (Aeromonadales, Enterobacteriaceae) occurred in both treatment groups, with incomplete normalization by days 631–633. Derangements in short-chain fatty acid, bile acid, indole, sphingolipid, benzoic acid, cinnaminic acid, and polyamine profiles also occurred, some of which persisted through the terminal sampling timepoint and differed between treatment groups. Discussion Cats administered clindamycin commonly develop AAGS, as well as short- and long-term dysbiosis and alterations in fecal metabolites. Despite a lack of differences in clinical signs between treatment groups, significant differences in their fecal metabolomic profiles were identified. Further investigation is warranted to determine whether antibiotic-induced dysbiosis is associated with an increased risk of future AAGS or metabolic diseases in cats and whether synbiotic administration ameliorates this risk.

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Mood and Global Symptom Changes among Psychotherapy Clients with Depressive Personality

Depression Research and Treatment ◽

10.1155/2012/208435 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12

Author(s):

Rachel E. Maddux ◽

Lars-Gunnar Lundh

Keyword(s):

Repeated Measures ◽

Mixed Model ◽

Psychological Symptoms ◽

Self Report ◽

Treatment Results ◽

Repeated Measures Analysis ◽

Depressive Personality ◽

Symptom Changes ◽

Psychotherapy Clients ◽

Over Time

The present study assessed the rate of depressive personality (DP), as measured by the self-report instrument depressive personality disorder inventory (DPDI), among 159 clients entering psychotherapy at an outpatient university clinic. The presenting clinical profile was evaluated for those with and without DP, including levels of depressed mood, other psychological symptoms, and global severity of psychopathology. Clients were followed naturalistically over the course of therapy, up to 40 weeks, and reassessed on these variables again after treatment. Results indicated that 44 percent of the sample qualified for DP prior to treatment, and these individuals had a comparatively more severe and complex presenting disposition than those without DP. Mixed-model repeated-measures analysis of variance was used to examine between-groups changes on mood and global severity over time, with those with DP demonstrating larger reductions on both outcome variables, although still showing more symptoms after treatment, than those without DP. Only eleven percent of the sample continued to endorse DP following treatment. These findings suggest that in routine clinical situations, psychotherapy may benefit individuals with DP.

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Abstract 299: Low Calorie Cranberry Juice Lowers Blood Pressure in Healthy Adults

Hypertension ◽

10.1161/hyp.60.suppl_1.a299 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Janet A Novotny ◽

David J Baer ◽

Christina Khoo ◽

Sarah K Gebauer

Keyword(s):

Blood Pressure ◽

Body Weight ◽

Diastolic Blood Pressure ◽

Repeated Measures ◽

Mixed Model ◽

Controlled Trial ◽

Healthy Adults ◽

Cranberry Juice ◽

Low Calorie ◽

Dietary Polyphenols

Dietary polyphenols have been shown to have a beneficial impact on blood pressure. To investigate the effect of daily consumption of a low calorie cranberry juice beverage (a rich source of polyphenols) on blood pressure of healthy adults (n=56), we conducted a parallel arm, double-blind, randomized, placebo-controlled trial. Volunteers were men (n=26) and women (n=30), aged 51+11 years, with a body weight of 79.3+8.8 kg and BMI of 28.4+4.3 (mean+SD). Treatments were a low calorie cranberry juice beverage or a color/flavor/calorie-matched placebo beverage, both of which were incorporated into a controlled diet for 8 weeks. During the controlled diet, volunteers consumed a base diet, consisting of typical American foods, scaled to meet their individual energy requirement such that body weight did not change during the study. Blood pressure was measured by a standardized protocol at the beginning of the intervention, after 4 weeks of treatment, and after 8 weeks of treatment. Systolic and diastolic blood pressure values for placebo and cranberry juice treatments at 4 weeks and 8 weeks were compared with a mixed model ANOVA. Blood pressure measures at 4 and 8 weeks of treatment for placebo and cranberry juice were also compared to baseline using a repeated measures ANOVA. After 8 weeks, diastolic blood pressure was significantly lower for the cranberry juice group compared to the placebo group (LSmeans + SEM of 72.2+1.1 mm Hg for placebo vs. 68.6+1.1 mm Hg for cranberry juice, respectively, p=0.029). When 8 week blood pressure values were compared to baseline, cranberry juice was associated with a significant decrease in diastolic BP (73.9+1.6 mm Hg at baseline vs. 70.9+1.6 mm Hg at 8 wk, p=0.049) and a trend toward decreased systolic BP (121.9+3.2 mm Hg at baseline vs. 118.6+3.1 mm Hg at 8 wk, p=0.12), while the placebo was associated with no change from baseline (systolic of 111.5+2.4 mm Hg at baseline vs. 112.3+2.2 mm Hg at 8 wk, p=0.89; diastolic of 68.1+1.5 mm Hg at baseline vs. 68.6+1.5 mm Hg at 8 wk, p=0.37). In conclusion, incorporation of a low calorie cranberry juice beverage into the diet of healthy adults appears to result in improvements in blood pressure.

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Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.5.937 ◽

1994 ◽

Vol 12 (5) ◽

pp. 937-945 ◽

Cited By ~ 136

Author(s):

J S Lee ◽

S M Lippman ◽

S E Benner ◽

J J Lee ◽

J Y Ro ◽

...

Keyword(s):

Repeated Measures ◽

Controlled Trial ◽

Squamous Metaplasia ◽

Bronchial Epithelium ◽

Controlled Study ◽

Bronchial Biopsy ◽

Treatment Groups ◽

Major Activity ◽

Complete Reversal ◽

Preclinical And Clinical Studies

PURPOSE Retinoids have proven chemopreventive efficacy in both preclinical and clinical studies. This trial was designed to confirm the finding of an earlier uncontrolled trial that the synthetic retinoid etretinate had major activity in reversing squamous metaplasia found in the bronchial epithelium of chronic smokers. PATIENTS AND METHODS We prospectively evaluated 152 smokers with bronchoscopy and obtained biopsies from six sites. Subjects with dysplasia and/or a metaplasia index of greater than 15% were randomly assigned to receive either 1 mg/kg isotretinoin or placebo daily for 6 months. Of 86 subjects randomized (41 isotretinoin, 45 placebo), 69 were reevaluated at the completion of treatment. RESULTS In the group as a whole, the metaplasia index decreased over time from a mean +/- SE of 35.8% +/- 2.7% at baseline to 28.1% +/- 3.3% at the completion of treatment (P = .01) by repeated measures analysis of variance [ANOVA]); a reduction in the metaplasia index (> 8%) was noted in both isotretinoin and placebo groups (19 of 35 [54.3%] and 20 of 34 [58.8%], respectively). Complete reversal of squamous metaplasia was noted in nine subjects from each group. However, the magnitudes of the mean metaplasia index changes did not differ significantly in the two treatment groups. In both groups, smoking cessation resulted in significant declines in the extent of squamous metaplasia, whereas no significant change in metaplasia index was found among those who continued to smoke. CONCLUSION Squamous metaplasia was frequently observed in bronchial biopsy samples from chronic smokers. From this study, we conclude that isotretinoin has no effect on squamous metaplasia, a potential intermediate end point of bronchial carcinogenesis. Although determining the exact role of isotretinoin in lung cancer prevention requires further study, the finding that there was a significant decrease in squamous metaplasia in the placebo group emphasizes the critical importance of a placebo-controlled study design in chemoprevention trials using intermediate end points.

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Impacts of rTMS on Refractory Depression and Comorbid PTSD Symptoms at a Military Treatment Facility

Military Medicine ◽

10.1093/milmed/usaa148 ◽

2020 ◽

Vol 185 (9-10) ◽

pp. e1420-e1427

Author(s):

Sean Wilkes ◽

Celia Ona ◽

Michael Yang ◽

Pingyang Liu ◽

Amber Benton ◽

...

Keyword(s):

Repeated Measures ◽

Mixed Model ◽

Repetitive Transcranial Magnetic Stimulation ◽

Active Duty ◽

Ptsd Symptoms ◽

Refractory Depression ◽

Antidepressant Medications ◽

Treatment Of Depression ◽

Changes Over Time ◽

Over Time

Abstract Introduction Repetitive transcranial magnetic stimulation (rTMS) as a treatment for depression has been studied for over two decades. Repetitive TMS was approved by the Food and Drug Administration in 2008 for the treatment of depression after at least one failed trial of an antidepressant medication of adequate dose and duration. This study evaluated whether rTMS treatments may be associated with measurable improvements in depression and post-traumatic stress disorder (PTSD) symptoms for treated military beneficiaries in Hawaii suffering from depression. It also examined the number of failed medication trials that patients underwent before rTMS treatment. Materials and Methods A retrospective chart review of 77 rTMS patients who received and completed treatment between January 1, 2010 and October 31, 2016 was performed. Under a typical treatment regimen, patients receive rTMS for 6 weeks as well as weekly psychiatric assessments, which included completion of Beck’s Depression Inventory (BDI) and PTSD Checklist (PCL). A mixed model repeated measures analysis was done assuming an autoregressive order one covariance structure to evaluate changes over time. Adjusted analyses were done to assess whether changes over time differed by age, prior diagnosis of PTSD, active duty status, and gender. Results The majority of patients were from the army (74%) and 56% were on active duty. Just over half (53%) were male. Most patients (52%) had completed trials of three or more different antidepressant medications before initiation of treatment with rTMS. The mean number of antidepressant trials was 2.7. BDI and PCL scores were significantly lower at end of treatment on average compared to the pretreatment baseline scores. Mean differences for BDI and PCL were significant with P < 0.001 15, 30, and 45 days after TMS treatment was initiated. Overall, 44% of patients experienced a reduction ≥10 points on BDI, and 38% experienced a reduction ≥10 points on PCL. Additionally, scores fell similarly regardless of whether or not patients had a comorbid diagnosis of PTSD. Conclusions Our research suggests that rTMS treatments may produce a reduction in symptoms of both depression and PTSD in patients with refractory depression and comorbid PTSD. It may be a useful alternative to antidepressants in the treatment of depression in the military population, including those with comorbid PTSD. Broader implementation of this treatment modality may prove beneficial for the purposes of military readiness, given current policies and restrictions on service members who are initiated on antidepressant medications.

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Effects of Exercise Restriction on Patients With Anomalous Aortic Origin of a Coronary Artery

World Journal for Pediatric and Congenital Heart Surgery ◽

10.1177/2150135116674444 ◽

2016 ◽

Vol 8 (1) ◽

pp. 18-24 ◽

Cited By ~ 6

Author(s):

Matthew D. Elias ◽

James Meza ◽

Brian W. McCrindle ◽

Julie A. Brothers ◽

Stephen Paridon ◽

...

Keyword(s):

Coronary Artery ◽

Exercise Capacity ◽

Repeated Measures ◽

Mixed Model ◽

Linear Mixed Model ◽

Multivariable Analysis ◽

Young Patients ◽

Significant Difference ◽

Exercise Restriction ◽

Over Time

Background: Management of young patients with anomalous aortic origin of a coronary artery (AAOCA) may involve exercise restriction. We sought to identify the association of exercise restriction with changes over time in body mass index (BMI) and exercise capacity in this cohort. Methods: We performed a retrospective review of patients with AAOCA seen at The Children’s Hospital of Philadelphia between January 1, 1998, and August 31, 2014. Linear mixed model repeated-measures analysis assessed changes in BMI and exercise capacity. Results: We included 72 patients with a median age at presentation of 12.6 years (interquartile range: 10.1-15.8) and mean follow-up of 3.6 ± 3.0 years. The majority had an anomalous right coronary artery (71%) and interarterial ± intramural coronary course (90%). Surgery was performed in 54%, more often in those with interarterial/intramural course ( P < .001) and symptoms ( P = .003). Most patients (82%) were exercise-restricted on presentation, and restricted patients were older than those who were not restricted ( P = .01). There was no significant difference between restricted and nonrestricted patients in initial BMI z scores, percentage of patients with BMI over 85th percentile (26%) or exercise capacity variables. In univariable analysis, exercise restriction over time was not associated with change in BMI z score ( P = .25) or change in exercise variables. Restriction was not associated with significant change in these variables in multivariable analysis. Conclusions: Although further investigation is warranted to determine the degree of adherence to exercise restriction, the recommendation of restriction alone is not associated with increasing BMI or decreasing exercise performance in the short-term.

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Efficacy of Exercise on Postneedling Soreness: A Randomized Controlled Trial

Journal of Clinical Medicine ◽

10.3390/jcm10235527 ◽

2021 ◽

Vol 10 (23) ◽

pp. 5527

Author(s):

Nicola Sante Diciolla ◽

Celia Pérez-Clemente ◽

Marta Cámara-Caballero ◽

Alberto Matienzo-Barreto ◽

Alba Real-Rodríguez ◽

...

Keyword(s):

Gastrocnemius Muscle ◽

Mixed Model ◽

Controlled Trial ◽

Isometric Exercise ◽

Pressure Pain Threshold ◽

Medial Gastrocnemius ◽

Post Intervention ◽

Myofascial Trigger Points ◽

Medial Gastrocnemius Muscle ◽

Over Time

This study aimed to investigate the efficacy of concentric, eccentric, and isometric exercise protocols on the postneedling soreness (PNS) after the dry needling (DN) of latent myofascial trigger points (MTrP) in the medial gastrocnemius muscle. A randomized clinical trial was carried out. Volunteers, ≥18 years old, with a latent MTrP in the medial gastrocnemius muscle were included. Subjects with contraindications to DN, active MTrPs, and/or other treatments in MTrPs in the 3 months prior to recruitment were excluded. A total of 69 participants were randomly allocated to four groups, where post-DN intervention consisted of an eccentric, concentric, or isometric exercise, or no exercise, and they were assessed for PNS intensity (visual analog scale (pVAS)), pressure pain threshold (PPT, analog algometer), pain intensity (nVAS), and local twitch responses (LTRs) during DN, as well as demographics and anthropometrics. The mixed-model analyses of variance showed significant interaction between time and pVAS, and between time and PPT (p < 0.001). While the multivariate test confirmed that PNS and PPT improved over time within each group, specifically between 6–12 h post-intervention, the post hoc analyses did not show significant differences between groups. The mixed-model analyses of covariance showed a significant nVAS effect (p < 0.01) on PNS decrease, and some effect of the LTRs (p < 0.01) and sex (p = 0.08) on PPT changes. All groups improved PNS and PPT, but none of them showed a greater improvement above the others. The most dramatic decrease was observed between 6–12 h post-exercise, although concentric and eccentric exercise had an effect immediately after the intervention. Between all potential modifiers, pain during DN significantly influenced PNS progression, while LTRs and sex seemed to determine PPT course over time.

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PROMs and PREMs in Dutch integrated head and neck cancer care.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.6570 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 6570-6570

Author(s):

Rosella Hermens ◽

Lydia Francisca Jacoba van Overveld ◽

Robert P. Takes ◽

Jozé C.C. Braspenning ◽

Ludi E Smeele ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Mixed Model ◽

Mixed Model Analysis ◽

Treatment Groups ◽

Patient Reported ◽

Over Time ◽

Domain Scores

6570 Background: Providing patient-centred care is an essential component of high quality integrated care. A method to get insight in patients perspectives about the quality of health care they received, is measuring Patient Reported Outcome Measures (PROMs) and Patient Reported Experience Measures (PREMs). We aimed to determine the outcomes of, and differences between PROs and PREs over time and between treatment groups for patients with head and neck cancer (HNC). Methods: Patientswere recruited from nine hospitals participating in the DHNA. Validated questionnaires were distributed at baseline, 3, 6 and 12 months follow-up. Included PROMs were EuroQol 5 Dimension 3 Level (EQ-5D-3L), EORTC QLQ-C30 and -H&N35. Included PREMs, Consumer Quality index for Oncologic care (CQO) and Radiotherapeutic care (CQR), have similar domains with different questions. With descriptive analysis, ANOVA and mixed model analysis, differences over time and between treatment groups were analyzed. Results: Questionnaires were filled in by 426 patients. Pain decreased significantly at 6 and 12 months follow-up (14 and 21 points on a scale of 0-100) and dry mouth increased significantly at 3, 6 and 12 months follow-up compared to baseline (35, 27 and 20 points). Sticky Salvia, problems with social eating and sense problems increased at 3 and 6 months follow-up, but were similar to the baseline score at 12 months follow-up. Pain and sticky saliva differed between radiotherapy and chemoradiotherapy or surgery and radiotherapy respectively (p≤0.05). Regarding the CQO domain scores, all treatment groups differed significantly from each other (p≤0.05), especially for the domain Personal input. There was no difference regarding the CQR domain scores. Recognizing the emotional side of HNC and guidance after the treatment scored low in patients. Conclusions: This study gives clues to improve healthcare according the experiences of the patient and we can predict more carefully the outcomes of the patients with different treatment types. PROMs according to the ICHOM criteria and PREMs are promising for measuring and improving quality and personalization of HNC care. However, recognizing the emotional side of HNC and intensifying guidance after the treatment period needs improvement.

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Abstract 52: Efficacy and Safety of Mipomersen in Patients with Familial Hypercholesterolemia and Inadequately Controlled LDL-C Levels

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.52 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Christie Ballantyne ◽

Alberico L Catapano ◽

Michael Davidson ◽

Robert Mittleman ◽

Patrick M Moriarty ◽

...

Keyword(s):

Adverse Events ◽

Familial Hypercholesterolemia ◽

Repeated Measures ◽

Mixed Model ◽

Primary Objective ◽

Tolerability Profile ◽

Primary Analysis ◽

Double Blind ◽

Absolute Reduction ◽

Over Time

Aim: Mipomersen is an antisense oligonucleotide inhibitor of apolipoprotein B-100 synthesis, FDA-approved to treat homozygous familial hypercholesterolemia. The primary objective of this study was to determine whether mipomersen significantly reduced atherogenic lipid levels in patients with severe heterozygous familial hypercholesterolemia (HeFH). Methods: This was a randomized, double-blind, placebo-controlled, parallel-group study comprised of two cohorts (NCT01475825). Cohort 1 had severe HeFH (LDL-C ≥200 mg/dL + coronary heart disease, or LDL-C ≥300 mg/dL) and Cohort 2 had milder HeFH (LDL-C ≥160 and <200 mg/dL). For each cohort, patients were randomized 1:1 to 200 mg SC once weekly or 70 mg SC thrice weekly, then 2:1 to receive mipomersen or placebo for 60 weeks. The primary outcome was percent change from baseline in LDL-C in Cohort 1. The % change from baseline in LDL-C at Week 61 for mipomersen treated patients was compared to placebo using a mixed model for repeated measures (MMRM), as well as by ANCOVA on the value closest to 7 days post last treatment (LOCF). Results: Mean baseline LDL-C levels were 265 mg/dL in Cohort 1 (N=200) and 176 mg/dL in Cohort 2 (N=109). In Cohort 1, mipomersen 200 mg weekly reduced LDL-C levels by -29.7% (vs -7.9% placebo, P <.001) in the mixed model, and by -36.3% (vs -7.6% placebo, P <.001) using the LOCF. Analysis of LDL-C over time (Figure) showed a mean absolute reduction of 138 mg/dL in mipomersen patients who completed the blinded treatment period (n=32), achieving a mean level of 147 mg/dL from a mean 285 mg/dL baseline level. Tolerability to treatment and adverse events were similar between dose regimens. Adverse events were consistent with the drug’s known safety and tolerability profile. Conclusions: The primary analysis showed a significant reduction in LDL-C levels in patients with severe HeFH who received mipomersen 200 mg once weekly versus placebo. A highly relevant absolute reduction in LDL-C was achieved over time.

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Effect of 6 weeks' consumption of β-glucan-rich oat products on cholesterol levels in mildly hypercholesterolaemic overweight adults

British Journal Of Nutrition ◽

10.1017/s0007114511003850 ◽

2011 ◽

Vol 107 (7) ◽

pp. 1037-1047 ◽

Cited By ~ 47

Author(s):

Karen E. Charlton ◽

Linda C. Tapsell ◽

Marijka J. Batterham ◽

Jane O'Shea ◽

Rebecca Thorne ◽

...

Keyword(s):

Total Cholesterol ◽

Repeated Measures ◽

Mixed Model ◽

Linear Mixed Model ◽

Controlled Trial ◽

Weight Maintenance ◽

Control Groups ◽

Regulatory Bodies ◽

Randomised Controlled ◽

And Control

Several regulatory bodies have approved a health claim on the cholesterol-lowering effects of oat β-glucan at levels of 3·0 g/d. The present study aimed to test whether 1·5 g/d β-glucan provided as ready-to-eat oat flakes was as effective in lowering cholesterol as 3·0 g/d from oats porridge. A 6-week randomised controlled trial was conducted in eighty-seven mildly hypercholesterolaemic ( ≥ 5 mmol/l and < 7·5 mmol/l) men and women assigned to one of three diet arms (25 % energy (E%) protein; 45 E% carbohydrate; 30 E% fat, at energy requirements for weight maintenance): (1) minimal β-glucan (control); (2) low-dose oat β-glucan (1·5 g β-glucan; oats low – OL) or (3) higher dose oat β-glucan (3·0 g β-glucan; oats high – OH). Changes in total cholesterol and LDL-cholesterol (LDL-C) from baseline were assessed using a linear mixed model and repeated-measures ANOVA, adjusted for weight change. Total cholesterol reduced significantly in all groups ( − 7·8 (sd 13·8) %, − 7·2 (sd 12·4) % and − 5·5 (sd 9·3) % in the OH, OL and control groups), as did LDL-C ( − 8·4 (sd 18·5) %, − 8·5 (sd 18·5) % and − 5·5 (sd 12·4) % in the OH, OL and control groups), but between-group differences were not significant. In responders only (n 60), β-glucan groups had higher reductions in LDL-C ( − 18·3 (sd 11·1) % and − 18·1 (sd 9·2) % in the OH and OL groups) compared with controls ( − 11·7 (sd 7·9) %; P = 0·044). Intakes of oat β-glucan were as effective at doses of 1·5 g/d compared with 3 g/d when provided in different food formats that delivered similar amounts of soluble β-glucan.

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