scholarly journals A Randomized Double Blind Controlled Safety Trial Evaluating D-Lactic Acid Production in Healthy Infants Fed a Lactobacillus reuteri-containing Formula

2014 ◽  
Vol 7 ◽  
pp. NMI.S14113 ◽  
Author(s):  
Konstantinos Papagaroufalis ◽  
Aikaterini Fotiou ◽  
Delphine Egli ◽  
Liên-Anh Tran ◽  
Philippe Steenhout
Keyword(s):  
Lactic Acid ◽  
Treatment Effect ◽  
Lactobacillus Reuteri ◽  
Lactic Acid Production ◽  
Fold Increase ◽  
Primary Objective ◽  
Double Blind ◽  
Term Infants ◽  
Healthy Infants ◽  
Colony Forming Units

Background D-Lactic acidosis in infants fed lactic acid bacteria-containing products is a concern. Methods The primary objective of this non-inferiority trial was to compare urinary D-lactic acid concentrations during the first 28 days of life in infants fed formula containing Lactobacillus reuteri (1.2 x 106 colony forming units (CFU)/ml) with those fed a control formula. The non-inferiority margin was set at a two-fold increase in D-lactic acid (0.7 mmol/mol creatinine, log-transformed). Healthy term infants in Greece were enrolled between birth and 72 hours of age, and block randomized to a probiotic ( N = 44) or control ( N = 44) group. They were exclusively fed their formulae until 28 days of age and followed up at 7, 14, 28, 112, and 168 ± 3 days. Anthropometric measurements were taken at each visit and tolerance recorded until 112 days. Urine was collected before study formula intake and at all visits up to 112 days and blood at 14 days. Results D-Lactic acid concentration in the probiotic group was below the non-inferiority margin at 28 days: treatment effect -0.03 (95% confidence interval [CI]: [-0.48 to 0.41]) mmol/mol creatinine but was above the non-inferiority margin at 7 and 14 days–-treatment effect 0.50 (95% CI: [0.05-0.96]) mmol/mol creatinine and 0.45 (95% CI: [0.00-0.90]) mmol/mol creatinine, respectively. Blood acid excess and pH, anthropometry, tolerance, and adverse events (AEs) were not significantly different between groups. Conclusion Intake of L. reuteri-containing formula was safe and did not cause an increase in D-lactic acid beyond two weeks. Trial Registration ClinicalTrials.gov NCT01119170.

Experience of implementing a novel random sampling BICR audit for investigator (INV)-assessed progression-free survival (PFS) in the PALOMA-3 trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1058-1058
Author(s):  
Xin Huang ◽  
Ke Zhang ◽  
Nicholas C. Turner ◽  
Cynthia Huang Bartlett ◽  
Carla Giorgetti ◽  
...  
Keyword(s):  
Random Sample ◽  
Primary Endpoint ◽  
Treatment Effect ◽  
Random Sampling ◽  
Randomized Clinical Trials ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Third Party ◽  
Double Blind

1058 Background: PFS has frequently been used as a primary endpoint for evaluating efficacy of anticancer therapies in randomized clinical trials. Given high correlation between INV and independent (BICR) assessments with respect to the relative treatment effect, a pre-planned BICR audit of INV progression assessment in a random subgroup of patients (pts) instead of a BICR review of all progression assessments can be an acceptable approach to verify the INV assessments and to evaluate the potential bias in INV PFS results. Methods: PALOMA-3 was a randomized, double blind, placebo (PCB) controlled, Ph 3 study with the primary objective of demonstrating the superiority of palbociclib (PAL) + fulvestrant (F) over PCB + F in women with HR+, HER2- metastatic breast cancer (MBC). The primary endpoint was INV assessed PFS. BICR assessment of PFS was performed with the use of a novel audit approach involving a random sample–based BICR to verify if the INV assessed PFS was accurate. A third-party core imaging laboratory performed the blinded review for a randomly selected subgroup of pts (~40%). NIH and PhRMA methods were used to evaluate the potential for bias in the INV PFS results. Results: PAL + F improved PFS in patients with HR+, HER2- MBC. The observed INV HR was 0.46 (95% CI: 0.36, 0.59; stratified 1-sided p < 0.0001) in favor of PAL + F. The median PFS was 9.5 mo (95% CI: 9.2, 11.0) in the PAL + F arm and 4.6 mo (95% CI: 3.5, 5.6) in the PCB + F arm (Lancet Oncol. 2016; 17: 425–39). The estimated HR of the complete BICR data incorporating the information from the complete INV assessed PFS and the random sample audited BICR subgroup was 0.33 with the upper bound of the 1-sided 95% CI of 0.47. The results confirmed the INV assessed treatment effect and detected no INV bias in favor of PAL + F. Conclusions: PALOMA-3 is the first registrational trial to use a BICR audit and has received positive reviews from regulatory agencies. The experience of implementing the random sampling BICR audit in PALOMA-3 demonstrates that this approach can be used for randomized, double blind oncology trials with solid tumors where INV assessed PFS is the primary endpoint and a large treatment effect is targeted. Sponsor: Pfizer. Clinical trial information: NCT01942135.

OVARIAN BIOCHEMICAL COMPETENCE FOLLOWING GONADOTROPHIC DEPRIVATION FROM BIRTH

1976 ◽  
Vol 82 (2) ◽  
pp. 388-395 ◽  
Author(s):  
Z. Kraiem ◽  
A. Eshkol ◽  
B. Lunenfeld ◽  
K. Ahrén
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Production ◽  
Fold Increase ◽  
Acute Effect ◽  
Hormonal Stimulation ◽  
Newborn Mice ◽  
Enzymatic Systems ◽  
Rat Ovary ◽  
And Control

ABSTRACT Normal ovarian morphogenesis is impaired by the absence of gonadotrophic hormones from birth. In the present study, the following question was asked: Does gonadotrophic deprivation also affect ovarian biochemical competence? Newborn mice were treated daily with an antiserum neutralizing endogenous circulating gonadotrophins. At the age of 14 days, ovaries from these mice and control littermates were incubated in the presence and absence of gonadotrophic preparations; cAMP and lactic acid levels were then measured in tissue and incubation medium. Ovaries from antigonadotrophin treated and control mice had the same basal levels, per mg tissue, of cAMP and lactic acid. Moreover, the levels increased to approximately the same extent following in vitro gonadotrophic stimulation: an increase in cAMP of 8–10-fold (using a preparation with an hLH:hFSH ratio of 1:1) or 2½-fold (using a preparation with an hLH:hFSH ratio of 1:5), and about a 2-fold increase in lactic acid (using oLH). The acute effect of gonadotrophins on ovarian glycolysis, reported up till now only in the rat ovary, is the first such demonstration in mice. The results also indicate that despite impaired morphogenesis, the enzymatic systems necessary for ovarian glycolysis (as measured by lactic acid production) and cAMP formation can develop without gonadotrophic participation. Furthermore, ovarian capacity to respond to hormonal stimulation is acquired post-natally, as shown by refractoriness to gonadotrophic stimulation during the first week of life. Finally, post-natal gonadotrophic exposure does not seem an essential requirement, at least as measured by the above parameters, for acquiring ovarian competence to respond to hormonal stimulation.

scholarly journals Regulating Oral Biofilm from Cariogenic State to Non-Cariogenic State via Novel Combination of Bioactive Therapeutic Composite and Gene-Knockout

2020 ◽  
Vol 8 (9) ◽  
pp. 1410
Author(s):  
Hong Chen ◽  
Yingming Yang ◽  
Michael D. Weir ◽  
Quan Dai ◽  
Lei Lei ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Gene Knockout ◽  
Lactic Acid Production ◽  
Dental Composite ◽  
Chain Reaction ◽  
Oral Biofilm ◽  
Biofilm Model ◽  
Colony Forming Units ◽  
Novel Method ◽  
Polymerase Chain

The objectives were to investigate a novel combination of gene-knockout with antimicrobial dimethylaminohexadecyl methacrylate (DMAHDM) composite in regulating oral biofilm from a cariogenic state toward a non-cariogenic state. A tri-species biofilm model included cariogenic Streptococcus mutans (S. mutans), and non-cariogenic Streptococcus sanguinis (S. sanguinis) and Streptococcus gordonii (S. gordonii). Biofilm colony-forming-units (CFUs), lactic acid and polysaccharide production were measured. TaqMan real-time-polymerase-chain reaction was used to determine the percentage of each species in biofilm. The rnc gene-knockout for S. mutans with DMAHDM composite reduced biofilm CFU by five logs, compared to control (p < 0.05). Using parent S. mutans, an overwhelming S. mutans percentage of 68.99% and 69.00% existed in biofilms on commercial composite and 0% DMAHDM composite, respectively. In sharp contrast, with a combination of S. mutans rnc knockout and DMAHDM composite, the cariogenic S. mutans percentage in biofilm was reduced to only 6.33%. Meanwhile, the non-cariogenic S. sanguinis + S. gordonii percentage was increased to 93.67%. Therefore, combining rnc-knockout with bioactive and therapeutic dental composite achieved the greatest reduction in S. mutans, and the greatest increase in non-cariogenic species, thereby yielding the least lactic acid-production. This novel method is promising to obtain wide applications to regulate biofilms and inhibit dental caries.

scholarly journals Long-Term Safety and Efficacy of Prebiotic Enriched Infant Formula—A Randomized Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1276
Author(s):  
Franka Neumer ◽  
Orenci Urraca ◽  
Joaquin Alonso ◽  
Jesús Palencia ◽  
Vicente Varea ◽  
...  
Keyword(s):  
Infant Formula ◽  
Controlled Trial ◽  
Fecal Microbiota ◽  
First Year ◽  
Double Blind Study ◽  
Double Blind ◽  
Term Infants ◽  
Intention To Treat ◽  
Prebiotic Oligosaccharides ◽  
First Year Of Life

The present study aims to evaluate the effects of an infant formula supplemented with a mixture of prebiotic short and long chain inulin-type oligosaccharides on health outcomes, safety and tolerance, as well as on fecal microbiota composition during the first year of life. In a prospective, multicenter, randomized, double-blind study, n = 160 healthy term infants under 4 months of age were randomized to receive either an infant formula enriched with 0.8 g/dL of Orafti®Synergy1 or an unsupplemented control formula until the age of 12 months. Growth, fever (>38 °C) and infections were regularly followed up by a pediatrician. Digestive symptoms, stool consistency as well as crying and sleeping patterns were recorded during one week each study month. Fecal microbiota and immunological biomarkers were determined from a subgroup of infants after 2, 6 and 12 months of life. The intention to treat (ITT) population consisted of n = 149 infants. Both formulae were well tolerated. Mean duration of infections was significantly lower in the prebiotic fed infants (p < 0.05). The prebiotic group showed higher Bifidobacterium counts at month 6 (p = 0.006), and higher proportions of Bifidobacterium in relation to total bacteria at month 2 and 6 (p = 0.042 and p = 0.013, respectively). Stools of infants receiving the prebiotic formula were softer (p < 0.05). Orafti®Synergy1 tended to beneficially impact total daily amount of crying (p = 0.0594). Supplementation with inulin-type prebiotic oligosaccharides during the first year of life beneficially modulates the infant gut microbiota towards higher Bifidobacterium levels at the first 6 months of life, and is associated with reduced duration of infections.

scholarly journals Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ekaterina Alexeeva ◽  
Gerd Horneff ◽  
Tatyana Dvoryakovskaya ◽  
Rina Denisova ◽  
Irina Nikishina ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Controlled Trial ◽  
Randomized Study ◽  
Primary Objective ◽  
Disease State ◽  
Inactive Disease ◽  
Open Label ◽  
Standard Regimen ◽  
Double Blind ◽  
Early Combination Therapy

Abstract Background Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.

scholarly journals Protective effect of titanium tetrafluoride and silver diamine fluoride on radiation-induced dentin caries in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Beatriz Martines de Souza ◽  
Mayara Souza Silva ◽  
Aline Silva Braga ◽  
Patrícia Sanches Kerges Bueno ◽  
Paulo Sergio da Silva Santos ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Protective Effect ◽  
Acid Production ◽  
Lactic Acid Production ◽  
Negative Control ◽  
Titanium Tetrafluoride ◽  
Silver Diamine Fluoride ◽  
Dentin Caries ◽  
Radiation Induced

AbstractThis in vitro study evaluated the protective effect of titanium tetrafluoride (TiF4) varnish and silver diamine fluoride (SDF) solution on the radiation-induced dentin caries. Bovine root dentin samples were irradiated (70 Gy) and treated as follows: (6 h): 4% TiF4 varnish; 5.42% NaF varnish; 30% SDF solution; placebo varnish; or untreated (negative control). Microcosm biofilm was produced from human dental biofilm (from patients with head-neck cancer) mixed with McBain saliva for the first 8 h. After 16 h and from day 2 to day 5, McBain saliva (0.2% sucrose) was replaced daily (37 °C, 5% CO2) (biological triplicate). Demineralization was quantified by transverse microradiography (TMR), while biofilm was analyzed by using viability, colony-forming units (CFU) counting and lactic acid production assays. The data were statistically analyzed by ANOVA (p < 0.05). TiF4 and SDF were able to reduce mineral loss compared to placebo and the negative control. TiF4 and SDF significantly reduced the biofilm viability compared to negative control. TiF4 significantly reduced the CFU count of total microorganism, while only SDF affected total streptococci and mutans streptococci counts. The varnishes induced a reduction in lactic acid production compared to the negative control. TiF4 and SDF may be good alternatives to control the development of radiation-induced dentin caries.

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