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The effects of synbiotic supplementation on blood pressure and other maternal outcomes in pregnant mothers with mild preeclampsia: a triple-blinded randomized controlled trial.
Movaghar, R, Abbasalizadeh, S, Vazifekhah, S, Farshbaf-Khalili, A, Shahnazi, M
BMC women's health. 2024;(1):80
Abstract
INTRODUCTION Preeclampsia affects a significant percentage of pregnancies which is a leading cause of premature birth. Probiotics have the potential to affect inflammatory factors, and oxidative stress, which are linked to the development of preeclampsia. The study aimed to compare the effect of synbiotic and placebo on blood pressure and pregnancy duration as primary outcomes, and other pregnancy outcomes. METHODS This study comprised 128 pregnant women with mild preeclampsia and gestational ages exceeding 24 weeks who were referred to the high-risk pregnancy clinic. It was a randomized, controlled, phase III, triple-blinded clinical experiment. The intervention and control groups were distributed to the participants at random. Intervention group received one oral synbiotic capsule, and control group received placebo daily until delivery. Based on gestational age at the time of diagnosis, preeclampsia was stratificated as early (< 34 weeks) or late (≥ 34 weeks). Data obtained from questionnaires, and biochemical serum factors were analyzed using SPSS software version 23 software. RESULTS With the exception of the history of taking vitamin D3, there were no statistically significant variations in socio-demographic variables between the research groups. After the intervention, the means of systolic blood pressure (adjusted mean difference: -13.54, 95% CI: -5.01 to -22.07), and diastolic blood pressure (adjusted mean difference: -10.30, 95% CI: -4.70 to -15.90) were significantly lower in the synbiotic-supplemented group than in the placebo group. Compared to the placebo group, the incidence of severe PE (p < 0.001), proteinuria (p = 0.044), and mean serum creatinine level (p = 0.005) significantly declined in the synbiotic-supplemented group after the intervention. However, our analysis found no significant association for other outcomes. CONCLUSION Based on our results, synbiotic had beneficial effects on some pregnancy outcomes. Further studies with larger samples are needed to verify the advantages of synbiotic supplementation for high-risk pregnancies, particularly with regards to higher doses, and longer intervention periods. TRIAL REGISTRATION IRCT20110606006709N20.
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Deep learning-based BMI inference from structural brain MRI reflects brain alterations following lifestyle intervention.
Finkelstein, O, Levakov, G, Kaplan, A, Zelicha, H, Meir, AY, Rinott, E, Tsaban, G, Witte, AV, Blüher, M, Stumvoll, M, et al
Human brain mapping. 2024;(3):e26595
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Obesity is associated with negative effects on the brain. We exploit Artificial Intelligence (AI) tools to explore whether differences in clinical measurements following lifestyle interventions in overweight population could be reflected in brain morphology. In the DIRECT-PLUS clinical trial, participants with criterion for metabolic syndrome underwent an 18-month lifestyle intervention. Structural brain MRIs were acquired before and after the intervention. We utilized an ensemble learning framework to predict Body-Mass Index (BMI) scores, which correspond to adiposity-related clinical measurements from brain MRIs. We revealed that patient-specific reduction in BMI predictions was associated with actual weight loss and was significantly higher in active diet groups compared to a control group. Moreover, explainable AI (XAI) maps highlighted brain regions contributing to BMI predictions that were distinct from regions associated with age prediction. Our DIRECT-PLUS analysis results imply that predicted BMI and its reduction are unique neural biomarkers for obesity-related brain modifications and weight loss.
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The Anatomic and Functional Outcomes of Ozurdex-Aided Vitrectomy in Proliferative Diabetic Retinopathy.
Wang, M, Luan, R, Liu, B, Gong, Y, Zhao, J, Chen, X, Yang, Q, Liu, J, Liu, J, Shao, Y, et al
Diabetes, metabolic syndrome and obesity : targets and therapy. 2024;:1199-1213
Abstract
PURPOSE To investigate the 3-months outcomes of patients who underwent intraoperative intravitreal injection of Ozurdex for proliferative diabetic retinopathy (PDR). METHODS This is a prospective randomized controlled clinical trial (ChiCTR2100043399). Seventy-one patients with PDR who had indications for surgery without intravitreal injection history within 3 months preoperatively were enrolled. Patients were randomly divided into three groups based on the medicine injected intraoperatively: Ozurdex, Conbercept, and Control group. The primary outcome is the best-corrected visual acuity (BCVA) within 3 months postoperatively. The secondary outcomes include the intraocular pressure (IOP), mean sensitivity, central retinal thickness and vessels perfusion. RESULTS The BCVA and the mean sensitivity improved in the three groups (F = 130.8, P < 0.0001; F = 34.18, P < 0.0001), but there was no statistical difference among the three groups (F = 0.858, P = 0.552; F = 0.964, P = 0.452). The IOP was no significant differences among the three groups within 3 months postoperatively (F = 0.881, P = 0.533). Compared with the other two groups, central retinal thickness (CRT) and outer retinal layer (ORL) thickness decreased significantly in patients of the Ozurdex group (F = 3.037, P = 0.008; F = 2.626, P = 0.018), especially in the diabetic macular edema (DME) patients (F = 2.761, P = 0.0164; F = 2.572, P = 0.0240). In macular region, superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) perfusion were not shown statistical difference at 3 months postoperatively in the all three groups compared with 1 day postoperatively (P > 0.05). CONCLUSION Compared with the other two groups, anatomical outcomes was improved significantly in Ozurdex group for DR patients. Ozurdex may help to improve the visual acuity and visual sensitivity, and there is no significant difference in the change of IOP and microvascular improvement. CLINICAL TRIAL REGISTRATION This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2100043399).
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Long-term efficacy and safety of a tetravalent dengue vaccine (TAK-003): 4·5-year results from a phase 3, randomised, double-blind, placebo-controlled trial.
Tricou, V, Yu, D, Reynales, H, Biswal, S, Saez-Llorens, X, Sirivichayakul, C, Lopez, P, Borja-Tabora, C, Bravo, L, Kosalaraksa, P, et al
The Lancet. Global health. 2024;(2):e257-e270
Abstract
BACKGROUND About half of the world's population lives in dengue-endemic areas. We aimed to evaluate the long-term efficacy and safety of two doses of the tetravalent dengue vaccine TAK-003 in preventing symptomatic dengue disease of any severity and due to any dengue virus (DENV) serotypes in children and adolescents. METHODS In this ongoing double-blind, randomised, placebo-controlled trial, we enrolled healthy participants aged 4-16 years at 26 medical and research centres across eight dengue-endemic countries (Brazil, Colombia, Dominican Republic, Nicaragua, Panama, Philippines, Sri Lanka, and Thailand). The main exclusion criteria were febrile illness (body temperature ≥38°C) at the time of randomisation, hypersensitivity or allergy to any of the vaccine components, pregnancy or breastfeeding, serious chronic or progressive disease, impaired or altered immune function, and previous receipt of a dengue vaccine. Participants were randomly assigned 2:1 (stratified by age and region) using an interactive web response system and dynamic block assignment to receive two subcutaneous doses of TAK-003 or placebo 3 months apart. Investigators, participants, and their parents or legal guardians were blinded to group assignments. Active febrile illness surveillance and RT-PCR testing of febrile illness episodes were performed for identification of virologically confirmed dengue. Efficacy outcomes were assessed in the safety analysis set (all randomly assigned participants who received ≥1 dose) and the per protocol set (all participants who had no major protocol violations), and included cumulative vaccine efficacy from first vaccination to approximately 4·5 years after the second vaccination. Serious adverse events were monitored throughout. This study is registered with ClinicalTrials.gov, NCT02747927. FINDINGS Between Sept 7, 2016, and March 31, 2017, 20 099 participants were randomly assigned (TAK-003, n=13 401; placebo, n=6698). 20 071 participants (10 142 [50·5%] males; 9929 [49·5%] females; safety set) received TAK-003 or placebo, with 18 257 (91·0%) completing approximately 4·5 years of follow-up after the second vaccination (TAK-003, 12 177/13 380; placebo, 6080/6687). Overall, 1007 (placebo: 560; TAK-003: 447) of 27 684 febrile illnesses reported were virologically confirmed dengue, with 188 cases (placebo: 142; TAK-003: 46) requiring hospitalisation. Cumulative vaccine efficacy was 61·2% (95% CI 56·0-65·8) against virologically confirmed dengue and 84·1% (77·8-88·6) against hospitalised virologically confirmed dengue; corresponding efficacies were 53·5% (41·6-62·9) and 79·3% (63·5-88·2) in baseline seronegative participants (safety set). In an exploratory analysis, vaccine efficacy was shown against all four serotypes in baseline seropositive participants. In baseline seronegative participants, vaccine efficacy was shown against DENV-1 and DENV-2 but was not observed against DENV-3 and low incidence precluded evaluation against DENV-4. During part 3 of the trial (approximately 22-57 months after the first vaccination), serious adverse events were reported for 664 (5·0%) of 13 380 TAK-003 recipients and 396 (5·9%) of 6687 placebo recipients; 17 deaths (6 in the placebo group and 11 in the TAK-003 group) were reported, none were considered study-vaccine related. INTERPRETATION TAK-003 demonstrated long-term efficacy and safety against all four DENV serotypes in previously exposed individuals and against DENV-1 and DENV-2 in dengue-naive individuals. FUNDING Takeda Vaccines. TRANSLATIONS For the Portuguese, Spanish translations and plain language summary of the abstract see Supplementary Materials section.
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Efficacy and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe in patients with dyslipidemia and hypertension: A randomized, double-blind, multicenter, therapeutic confirmatory, phase III clinical trial.
Lee, CJ, Kang, WC, Ihm, SH, Sohn, IS, Woo, JS, Kim, JW, Hong, SJ, Choi, JH, Suh, JW, Seo, JB, et al
Journal of clinical hypertension (Greenwich, Conn.). 2024;(3):262-273
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This study aimed to compare and evaluate the efficacy of the blood pressure (BP) control and cholesterol-lowering effects and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe versus rosuvastatin and ezetimibe double therapy or telmisartan single therapy in dyslipidemia patients with hypertension. After a wash-out/therapeutic lifestyle change period of ≥4 weeks, a total of 100 eligible patients were randomized and received one of three treatments for 8 weeks: (1) telmisartan 80 mg/rosuvastatin 20 mg/ezetimibe 10 mg (TRE), (2) rosuvastatin 20 mg/ezetimibe 10 mg (RE), or (3) telmisartan 80 mg (T). The primary endpoint was the efficacy evaluation of TRE by comparing changes in mean sitting systolic blood pressure (msSBP) and mean percentage change in low-density lipoprotein-C (LDL-C) from baseline after 8 weeks of treatment. The least square (LS) mean (SE) changes in msSBP at 8 weeks compared with baseline were -23.02 (3.04) versus -7.18 (3.09) mmHg in the TRE and RE groups, respectively (p < .0001), and -25.80 (2.74) versus -14.92 (2.65) mmHg in the TRE and T groups, respectively (p = .0005). The percentage changes in the mean (SD) LDL-C at 8 weeks compared with baseline were -54.97% (3.49%) versus -0.17% (3.23%) in the TRE and T groups, respectively (p < .0001). No serious adverse events occurred, and no statistically significant differences in the incidence of overall AEs and adverse drug reactions occurred among the three groups. TRE therapy significantly decreased msSBP and LDL-C compared to RE or T therapy with comparable safety and tolerability profiles.
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Comparison of passive-scattered and intensity-modulated proton beam therapy of craniospinal irradiation with proton beams for pediatric and young adult patients with brain tumors.
Fukumitsu, N, Kubota, H, Demizu, Y, Suzuki, T, Hasegawa, D, Kosaka, Y, Kawamura, A, Soejima, T
Japanese journal of radiology. 2024;(2):182-189
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PURPOSE To investigate the dose stability of craniospinal irradiation based on irradiation method of proton beam therapy (PBT). METHODS AND MATERIALS Twenty-four pediatric and young adult brain tumor patients (age: 1-24 years) were examined. Treatment method was passive-scattered PBT (PSPT) in 8 patients and intensity-modulated PBT (IMPT) in 16 patients. The whole vertebral body (WVB) technique was used in 13 patients whose ages were younger than 10, and vertebral body sparing (VBS) technique was used for the remaining 11 patients aged 10 and above. Dose stability of planning target volume (PTV) against set-up error was investigated. RESULTS The minimum dose (Dmin) of IMPT was higher than that of PSPT (p = 0.01). Inhomogeneity index (INH) of IMPT was lower than that of PSPT (p = 0.004). When the irradiation field of the cervical spinal cord level (C level) was shifted, the maximum dose (Dmax) was lower in IMPT, and mean dose (Dmean) was higher than PSPT as movement became greater to the cranial-caudal direction (p = 0.000-0.043). Dmin was higher and INH was lower in IMPT in all directions (p = 0.000-0.034). When the irradiation field of the lumber spinal cord level (L level) was shifted, Dmax was lower in IMPT as movement became greater to the cranial direction (p = 0.000-0.028). Dmin was higher and INH was lower in IMPT in all directions (p = 0.000-0.022). CONCLUSIONS The PTV doses of IMPT and PSPT are robust and stable in both anterior-posterior and lateral directions at both C level and L level, but IMPT is more robust and stable than PSPT for cranial-caudal movements. TRIAL REGISTRY Clinical Trial Registration number: No. 04-03.
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Safety, pharmacokinetics, and pharmacodynamics in healthy Chinese volunteers treated with SC0062, a highly selective endothelin-A receptor antagonist.
Liu, Y, Wang, W, Qian, H, Gui, Y, Wang, Y, Song, R, Chen, Q, Rowinsky, E, Wang, S, Liang, X, et al
Clinical and translational science. 2024;(3):e13750
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This study evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and food effects (FE) of SC0062, a highly active endothelin-A (ETA ) receptor antagonist, in healthy subjects. The primary objectives of this first-in-human phase I study, comprised of single-ascending-dose, multiple-ascending-dose, and FE parts, were to characterize the safety and tolerability of SC0062, and FE. The secondary objectives were to determine the PK behavior of SC0062 and its major active metabolite M18, whereas exploratory objectives focused on PD effects, principally effects on endothelin-1 (ET-1) and total bile acids (TBA). Single doses of 10 to 100 mg and multiple daily doses of 20 and 50 mg for 6 days were well tolerated. SC0062 was rapidly absorbed and plasma exposure of SC0062 and M18 increased disproportionately with dose, achieving steady state by day 3, with accumulation ratios of 1.22 and 1.89 on day 6 for SC0062 and M18, respectively. The geometric mean (geometric standard deviation) terminal elimination half-life (t1/2 ) values of SC0062 and M18 were 7.25 (1.70) h and 13.73 (1.32) h, respectively. Plasma ET-1 concentrations were dose-proportional, whereas plasma TBA concentrations behaved erratically. Following a single 50 mg dose of SC0062 after a high-fat meal, Cmax values for SC0062 and M18 increased by 41% and 32%, respectively, and median Tmax values for SC0062 were 3 h longer than fasting values; exposure was unaffected. These favorable safety, PK, and PD results provide a foundation for further studies of SC0062 in pulmonary arterial hypertension, chronic kidney disease, and other relevant indications.
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Efficacy and Safety of BB-12 Supplemented Strawberry Yogurt For Healthy Children on Antibiotics (PLAY ON).
Merenstein, D, Sparenborg, J, Tan, T, D'Amico, F, Kumar, A, Herbin Smith, K
Annals of family medicine. 2024;(Suppl 3)
Abstract
Context: Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. One of the most common indications for probiotic treatment is the prevention of antibiotic-associated diarrhea (AAD). Unfortunately, many probiotic products used for AAD are not supported by rigorous independent research, and often results in non-evidence-based usage. The overarching objective is to move research forward for the most well-studied Bifidobacterium strain. Objectives: The primary aim is to test the efficacy of high dose, BB-12-supplemented yogurt in preventing AAD, compared to yogurt without BB-12, in children receiving antibiotics. Other aims are to further assess the safety of yogurt supplemented with BB-12, and to carry out longitudinal community structure and gene expression analysis of fecal microbiota to evaluate the impact of high dose BB-12 in a pediatric population receiving antibiotics. The microbiota includes hundreds of species, and its disruption is hypothesized to be an important factor in the development of AAD. AIM 1: To test the efficacy of high dose, BB-12-supplemented yogurt in preventing AAD, compared to yogurt without BB-12, in children receiving antibiotics. Hypothesis: Children receiving antibiotics who receive the yogurt with BB-12 will demonstrate less diarrhea than those receiving a control yogurt without BB-12. This is a Phase II trial that requires additional safety evaluation of high dose BB-12. Hypotheses 3: Administration of antibiotics will alter the composition and gene expression profile of the gut microbiota in pediatric patients, and concomitant ingestion of BB-12 in yogurt will mitigate the antibiotic-induced disturbance in the gut microbiota, as identified using 16S rRNA and metatranscriptomic profiling. Study Design and Analysis: We will finish in the June 2023 a Phase II, randomized, doubleblinded controlled trial with allocation concealment. Setting: Capital Areal Primary Care Practice Based Research Network. Population Studied: 270 patients, ages 3-12 years, clinically diagnosed with a respiratory infection requiring 7-10 days of antibiotics. Interventions: The two arms are, BB-12-supplemented yogurt and non-supplemented control yogurt, in a 1:1 randomized allocation. Participants of all ages will be asked to consume the same dose, 100 ml, of product per day. The 100 ml serving of probiotic yogurt will deliver ≥1010 CFU of BB-12. The BB-12 probiotic was not be added.
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Dupilumab demonstrated efficacy and was well tolerated regardless of prior use of swallowed topical corticosteroids in adolescent and adult patients with eosinophilic oesophagitis: a subgroup analysis of the phase 3 LIBERTY EoE TREET study.
Bredenoord, AJ, Dellon, ES, Hirano, I, Lucendo, AJ, Schlag, C, Sun, X, Glotfelty, L, Mannent, L, Maloney, J, Laws, E, et al
Gut. 2024;(3):398-406
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OBJECTIVE To assess the effect of long-term dupilumab on histological, symptomatic and endoscopic aspects of eosinophilic oesophagitis (EoE) in adolescent and adult patients with and without prior use of swallowed topical corticosteroids (STC) or prior inadequate response, intolerance or contraindication to STC. DESIGN Pre-specified analysis of data from the phase 3 LIBERTY EoE TREET study on patients who received dupilumab 300 mg once a week or placebo for 24 weeks (W24) in parts A and B, and an additional 28 weeks (W52) in part C. Patients were categorised as with/without prior STC use and with/without inadequate/intolerance/contraindication to STC. The proportion of patients achieving ≤6 eosinophils per high-power field (eos/hpf), absolute change in Dysphagia Symptom Questionnaire (DSQ) score, mean change in Endoscopic Reference Score and Histologic Scoring System grade/stage scores were assessed for each subgroup. RESULTS Regardless of prior STC use, dupilumab increased the proportion of patients achieving ≤6 eos/hpf and improved DSQ score versus placebo at W24, with improvements maintained or improved at W52. The DSQ score and the proportion of patients achieving ≤6 eos/hpf after switching from placebo to dupilumab at W24 were similar to those observed in the dupilumab group at W24, regardless of prior STC use or inadequate/intolerance/contraindication to STC. Improvements in other outcomes with dupilumab were similar in patients with/without prior STC use or inadequate/intolerance/contraindication to STC. CONCLUSION Dupilumab 300 mg once a week demonstrated efficacy and was well tolerated in patients with EoE regardless of prior STC use or inadequate response, intolerance and/or contraindication to STC. TRIAL REGISTRATION NUMBER NCT03633617.
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The RIVET RCT: Rifamycin SV MMX improves muscle mass, physical function, and ammonia in cirrhosis and minimal encephalopathy.
Bajaj, JS, Fagan, A, Gavis, EA, Mousel, T, Gallagher, ML, Puri, P, Fuchs, M, Davis, BC, Hylemon, PB, Zhou, H, et al
Hepatology communications. 2024;(2)
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BACKGROUND Minimal hepatic encephalopathy (MHE) negatively affects the prognosis of cirrhosis, but treatment is not standard. Rifamycin SV MMX (RiVM) is a nonabsorbable rifampin derivative with colonic action. METHODS In a phase 2 placebo-controlled, double-blind randomized clinical trial patients with MHE were randomized to RiVM or placebo for 30 days with a 7-day follow-up. The primary endpoint was a change in stool cirrhosis dysbiosis ratio. Gut-brain (cognition, stool/salivary microbiome, ammonia, brain magnetic resonance spectroscopy), inflammation (stool calprotectin/serum cytokines), patient-reported outcomes (sickness impact profile: total/physical/psychosocial, high = worse), and sarcopenia (handgrip, bioelectric impedance) were secondary. Between/within groups and delta (post-pre) comparisons were performed. RESULTS Thirty patients (15/group) were randomized and completed the study without safety concerns. While cirrhosis dysbiosis ratio was statistically similar on repeated measures ANOVA (95% CI: -0.70 to 3.5), ammonia significantly reduced (95% CI: 4.4-29.6) in RiVM with changes in stool microbial α/β-diversity. MHE status was unchanged but only serial dotting (which tests motor strength) improved in RiVM-assigned patients. Delta physical sickness impact profile (95% CI: 0.33 = 8.5), lean mass (95% CI: -3.3 to -0.9), and handgrip strength (95% CI: -8.1 to -1.0) improved in RiVM versus placebo. Stool short-chain fatty acids (propionate, acetate, and butyrate) increased post-RiVM. Serum, urine, and stool bile acid profile changed to nontoxic bile acids (higher hyocholate/ursodeoxycholate and lower deoxycholate/lithocholate) post-RiVM. Serum IL-1β and stool calprotectin decreased while brain magnetic resonance spectroscopy showed higher glutathione concentrations in RiVM. CONCLUSIONS RiVM is well tolerated in patients with MHE with changes in stool microbial composition and function, ammonia, inflammation, brain oxidative stress, and sarcopenia-related parameters without improvement in cognition. RiVM modulates the gut-brain axis and gut-muscle axis in cirrhosis.