Impact of Carbohydrate Counting Method during Pregnancy in Women with Pregestational Diabetes Mellitus: A Controlled Clinical Trial.
Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia. 2022;(3):220-230
OBJECTIVE To evaluate the effect of the carbohydrate counting method (CCM) on glycemic control, maternal, and perinatal outcomes of pregnant women with pregestational diabetes mellitus (DM). METHODS Nonrandomized controlled clinical trial performed with 89 pregnant women who had pregestational DM and received prenatal care in a public hospital in Rio de Janeiro, state of Rio de Janeiro, Brazil, between 2009 and 2014, subdivided into historic control group and intervention group, not simultaneous. The intervention group (n = 51) received nutritional guidance from the carbohydrate counting method (CCM), and the historical control group (n = 38), was guided by the traditional method (TM). The Mann-Whitney test or the Wilcoxon test were used to compare intra- and intergroup outcomes and analysis of variance (ANOVA) for repeated measures, corrected by the Bonferroni post-hoc test, was used to assess postprandial blood glucose. RESULTS Only the CCM group showed a reduction in fasting blood glucose. Postprandial blood glucose decreased in the 2nd (p = 0.00) and 3rd (p = 0.00) gestational trimester in the CCM group, while in the TM group the reduction occurred only in the 2nd trimester (p = 0.015). For perinatal outcomes and hypertensive disorders of pregnancy, there were no differences between groups. Cesarean delivery was performed in 82% of the pregnant women and was associated with hypertensive disorders (gestational hypertension or pre-eclampsia; p = 0.047). CONCLUSION Both methods of nutritional guidance contributed to the reduction of postprandial glycemia of women and no differences were observed for maternal and perinatal outcomes. However, CCM had a better effect on postprandial glycemia and only this method contributed to reducing fasting blood glucose throughout the intervention. REBEC CLINICAL TRIALS DATABASE The present study was registered in the ReBEC Clinical Trials Database (Registro Brasileiro de Ensaios Clínicos, number RBR-524z9n).
A Pre-Phase III Efficacy Trial of the Spermicide/Contraceptive Effect of the Invisible Condom, a Non-Hormonal Vaginal Gel, in Women from Canada.
Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC. 2022;(2):175-181
OBJECTIVES To evaluate the spermicidal efficacy of non-hormonal vaginal gel in vitro and in a post-coital test, and to evaluate its contraceptive efficacy in Canadian women of childbearing age. METHODS We conducted single-centre trial to assess spermicidal and contraceptive efficacy of vaginal gel. Participants were healthy, sexually active women aged 18-49 years and their regular male sexual partners (30 couples). Measured outcomes included effect of vaginal gel on sperm motility in vitro, its effect on sperm in a post-coital test, and its effect on pregnancy prevention over 3 months. RESULTS For in vitro spermicidal effect, 98% and 67% of sperm were immotile in the presence of the gel with sodium lauryl sulfate (gel-SLS) and gel alone, respectively. For the post-coital test, 99% and 93% of sperm were immotile in the presence of gel-SLS and gel alone, respectively. In the second part of trial, a total of 410 instances of vaginal intercourse in 95 menstrual cycles were protected (during 3-month period of gel-SLS use before each sexual intercourse with probability of 24 conceptions prevented according to Wilcox's table). Four women became pregnant during the study period; 2 during unprotected vaginal intercourse around the time of ovulation, and 2 attributed to user failure. CONCLUSION Based on our results, the vaginal gel demonstrated important spermicidal and contraceptive effect. A larger phase III contraceptive efficacy trial is warranted. The vaginal gel may represent a non-hormonal spermicide/contraceptive option for women.
Safety and Glycemic Outcomes With a Tubeless Automated Insulin Delivery System in Very Young Children With Type 1 Diabetes: A Single-Arm Multicenter Clinical Trial.
Diabetes care. 2022;(8):1907-1910
OBJECTIVE Very young children with type 1 diabetes often struggle to achieve glycemic targets, putting them at risk for long-term complications and creating an immense management burden for caregivers. We conducted the first evaluation of the Omnipod 5 Automated Insulin Delivery System in this population. RESEARCH DESIGN AND METHODS A total of 80 children aged 2.0-5.9 years used the investigational system in a single-arm study for 13 weeks following 14 days of baseline data collection with their usual therapy. RESULTS There were no episodes of severe hypoglycemia or diabetic ketoacidosis. By study end, HbA1c decreased by 0.55% (6.0 mmol/mol) (P < 0.0001). Time with sensor glucose levels in target range 70-180 mg/dL increased by 10.9%, or 2.6 h/day (P < 0.0001), while time with levels <70 mg/dL declined by median 0.27% (P = 0.0204). CONCLUSIONS Use of the automated insulin delivery system was safe, and participants experienced improved glycemic measures and reduced hypoglycemia during the study phase compared with baseline.
Effect of Rice (Oryza sativa L.) Ceramides Supplementation on Improving Skin Barrier Functions and Depigmentation: An Open-Label Prospective Study.
Ceramides plays a crucial role in maintaining skin barrier function. Although foregoing evidence supported beneficial effects of topical ceramides for restoration of the skin barrier, studies on oral ceramides are extremely scarce, with most published data collected from in vivo and in vitro models. Thus, this study aimed to evaluate the efficacy of rice ceramides (RC) supplementation to improve skin barrier function and as a depigmenting agent through comprehensive clinical assessments. This study investigated the beneficial effects of orally administered RC supplementation in 50 voluntary participants. Skin hydration, firmness and elasticity, transepidermal water loss (TEWL), melanin index (MI), erythema index (EI), sebum production, pH, and wrinkle severity were assessed at baseline and during monthly follow-up visits. RC supplementation was found to significantly (p < 0.01) improve skin hydration, sebum production, firmness and elasticity, and wrinkle severity for three assessed areas, namely the left cheek, dorsal neck, and right inner forearm. Additionally, RC significantly (p < 0.01) reduced the rates of TEWL, levels of MI and EI. Analyses of data indicated that participants at older age were more responsive towards the effect of RC supplementation. Our findings suggest that RC supplementation can effectively improve skin barrier function, reduce wrinkle severity, and reduce pigmentation.
Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of OPC-61815, a Prodrug of Tolvaptan for Intravenous Administration, in Patients With Congestive Heart Failure - A Phase II, Multicenter, Double-Blind, Randomized, Active-Controlled Trial.
Circulation journal : official journal of the Japanese Circulation Society. 2022;(4):699-708
BACKGROUND Tolvaptan is an orally administered aquaretic drug indicated for patients with congestive heart failure (CHF) to remove excess fluid. OPC-61815, a prodrug of tolvaptan with improved water solubility, is considered suitable for intravenous (IV) administration. This Phase II study investigated the OPC-61815 dose that would result in an exposure equivalent to tolvaptan 15 mg.Methods and Results:We conducted a multicenter, randomized study in Japanese patients aged 20-85 years with CHF and volume overload despite treatment with diuretics other than vasopressin antagonists. Patients received IV OPC-61815 2 mg (n=13), 4 mg (n=12), 8 mg (n=12), 16 mg (n=11), or oral tolvaptan 15 mg (n=12). The primary endpoint was tolvaptan exposure on treatment Day 1; efficacy and safety were also assessed. Tolvaptan exposure increased in a dose-dependent manner following a single IV administration of OPC-61815; the exposure following an IV dose of OPC-61815 16 mg was similar to that of a tolvaptan 15-mg tablet, with no marked differences in safety or tolerability. OPC-61815 increased urine volume from baseline, resulting in decreased body weight and improved lower limb edema. No notable safety concerns were observed. CONCLUSIONS In this first study of OPC-61815 in patients with CHF, exposure following a single IV administration of OPC-61815 16 mg was comparable with a single oral administration of tolvaptan 15 mg, with no safety concerns.
Randomized Controlled Phase II Evaluation of Two Dose Levels of Bupropion Versus Placebo for Sexual Desire in Female Cancer Survivors: NRG-CC004.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2022;(4):324-334
PURPOSE Because of the negative impact of cancer treatment on female sexual function, effective treatments are warranted. The purpose of this multisite study was to evaluate the ability of two dose levels of extended-release bupropion, a dopaminergic agent, to improve sexual desire more than placebo at 9 weeks, measured by the desire subscale of the Female Sexual Function Index (FSFI), and to evaluate associated toxicities. METHODS Postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (< 3.3), who had completed definitive cancer therapy, were eligible. Women were randomly assigned to receive 150 mg or 300 mg once daily of extended-release bupropion or a matching placebo. t-tests were performed on the FSFI desire subscale to evaluate whether there was a significantly greater change from baseline to 9 weeks between placebo and each bupropion arm as the primary end point. Sixty-two patients per arm provided 80% power using a one-sided t-test. RESULTS Two hundred thirty women were randomly assigned from 72 institutions through the NRG Oncology NCORP network. At 9 weeks, there were no statistically significant differences in change of the desire subscale scores between groups; participants in all three arms reported improvement. The mean changes for each arm were placebo 0.62 (standard deviation [SD] = 1.18), 150-mg once daily bupropion 0.64 (SD = 0.95), and 300-mg once daily bupropion 0.60 (SD = 0.89). Total and subscale scores on the FSFI were low throughout the study, indicating dysfunction in all groups. CONCLUSION Bupropion was not more effective than placebo in improving the desire subscale of the FSFI. Subscale and total scores of the FSFI demonstrated dysfunction throughout the 9 weeks of the study. More research is needed to support sexual function in female cancer survivors.
Association of proteomic markers with nutritional risk and response to nutritional support: A secondary pilot study of the EFFORT trial using an untargeted proteomics approach.
Clinical nutrition ESPEN. 2022;:282-290
BACKGROUND By means of a structured nutritional support intervention, EFFORT showed a risk reduction for adverse events in medical in-patients. We were interested in the prognostic and therapeutic potential of an untargeted proteomics approach to understand response to nutritional support, risk of 30-day mortality, and distinct patterns in severity of malnutrition risk as assessed by the Nutritional Risk screening (NRS 2002), respectively. METHODS From 2,088 patients, we randomly took 120 blood samples drawn before treatment initiation on day 1 after hospital admission. Cases were selected by treatment allocation (nutritional support vs. usual nutrition), NRS 2002, and mortality at 30 days, but not on disease type. We measured proteins by untargeted liquid chromatography mass spectrometry (LC-MS/MS). RESULTS We found 242 distinct proteins in 120 patients of which 81 (67.5%) survived until day 30. Between group analysis revealed a slight difference between the treatment groups in patients with a NRS 3, but not in those with a higher NRS. C-statistic between non-survivors and survivors at day 30 ranged from 0.60 (95% confidence interval 0.34-0.78) for a combination of 3 proteins/predictors to 0.65 (95% CI 0.53-0.78) for a combination of 32 proteins/predictors. In nutritional support non-survivors, pathway analysis found significant enrichment in pathways for signal transduction, platelet function, immune system regulation, extracellular matrix organization, and integrin cell surface interactions compared to survivors. CONCLUSION Within this pilot study using an untargeted proteomics approach, there was only little prognostic and therapeutic potential of proteomics for phenotyping the risk of malnutrition and response to nutritional therapy. The small sample size and high heterogeneity of our population regarding comorbidity burden calls for more targeted approaches in more homogenous populations to understand the true potential of proteomics for individualizing nutritional care. TRIAL REGISTRATION This is a pre-planned secondary analysis of the EFFORT trial (ClinicalTrials.gov NCT02517476).
Pharmacological ascorbate improves the response to platinum-based chemotherapy in advanced stage non-small cell lung cancer.
Redox biology. 2022;:102318
PURPOSE Platinum-based chemotherapy with or without immunotherapy is the mainstay of treatment for advanced stage non-small cell lung cancer (NSCLC) lacking a molecular driver alteration. Pre-clinical studies have reported that pharmacological ascorbate (P-AscH-) enhances NSCLC response to platinum-based therapy. We conducted a phase II clinical trial combining P-AscH- with carboplatin-paclitaxel chemotherapy. EXPERIMENTAL DESIGN Chemotherapy naïve advanced stage NSCLC patients received 75 g ascorbate twice per week intravenously with carboplatin and paclitaxel every three weeks for four cycles. The primary endpoint was to improve tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 compared to the historical control of 20%. The trial was conducted as an optimal Simon's two-stage design. Blood samples were collected for exploratory analyses. RESULTS The study enrolled 38 patients and met its primary endpoint with an objective response rate of 34.2% (p = 0.03). All were confirmed partial responses (cPR). The disease control rate was 84.2% (stable disease + cPR). Median progression-free and overall survival were 5.7 months and 12.8 months, respectively. Treatment-related adverse events (TRAE) included one grade 5 (neutropenic fever) and five grade 4 events (cytopenias). Cytokine and chemokine data suggest that the combination elicits an immune response. Immunophenotyping of peripheral blood mononuclear cells demonstrated an increase in effector CD8 T-cells in patients with a progression-free survival (PFS) ≥ 6 months. CONCLUSIONS The addition of P-AscH- to platinum-based chemotherapy improved tumor response in advanced stage NSCLC. P-AscH- appears to alter the host immune response and needs further investigation as a potential adjuvant to immunotherapy.
Consistently High Agreement Between Independent Raters of Niemann-Pick Type C1 Clinical Severity Scale in Phase 2/3 Trial.
Pediatric neurology. 2022;:32-38
BACKGROUND Niemann-Pick disease, type C1 (NPC1) is a rare neurodegenerative genetic disorder characterized by impaired intracellular transport of cholesterol and other lipids. The Niemann-Pick Disease, type C1 Severity Scale (NPC-SS) was developed to quantify neurological progression of NPC; it is used to monitor the natural history of disease progression and assess response to treatment. The objective of the study was to examine the interrater reliability of the NPC-SS in a phase 2/3 trial. METHODS Study data were from a multicenter, prospective, randomized, double-blind trial of adrabetadex in 56 subjects with NPC1. Clinical data recorded at each study site were distributed to two independent blinded central raters to generate a severity score. A composite four-item score was utilized as the primary clinical study end point, whereas a five-item focused score has been utilized in other NPC1 trials. Interrater reliability was assessed using two-way mixed models for instrument stability, Cohen kappa, weighted kappa, and percent agreement for the four- and five-item scores. RESULTS The frequency distribution and mean (S.D.) of the NPC-SS domain assessments by the raters were almost identical. Evaluation at the patient visit level showed wide variability between visits; however, weighted kappa calculation provided a lower variability between visits. The average kappa coefficients ranged between 0.69 and 0.89, indicating good to very good agreement between raters. CONCLUSIONS These results support the NPC-SS, including derived four- and five-item composite scores, as reliable measures for use in a clinical trial setting.
Multikinase Inhibitors for the Treatment of Asymptomatic Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Global Noninterventional Study (RIFTOS MKI).
Thyroid : official journal of the American Thyroid Association. 2022;(9):1059-1068
Background: Sorafenib and lenvatinib are multikinase inhibitors (MKIs) approved for patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC). There is no consensus on when to initiate MKI treatment. The objective of this study was to evaluate time to symptomatic progression (TTSP) in patients with RAI-R DTC for whom the decision to treat with an MKI was made at study entry. Methods: International, prospective, open-label, noninterventional cohort study (NCT02303444). Eligible patients had asymptomatic progressive RAI-R DTC, with ≥1 lesion ≥1 cm in diameter and life expectancy ≥6 months. The decision to treat with an MKI was at the treating physician's discretion. Primary endpoint was TTSP from study entry. Two cohorts were evaluated: patients for whom a decision to initiate an MKI was made at study entry (Cohort 1) and patients for whom there was a decision not to initiate an MKI at study entry (Cohort 2). Cohorts were compared descriptively. Results: The full analysis set (FAS) comprised 647 patients. The median duration of observation was 35.5 months (range <1-59.4). Of 344 MKI-treated patients, 209 received sorafenib, 191 received lenvatinib, and 19 received another MKI at some point. Median TTSP was 55.4 months (interquartile range [IQR] 18.6-not estimable [NE]) overall, 55.4 months (IQR 15.2-NE) in Cohort 1 (n = 169), and 51.4 months (IQR 20.0-NE) in Cohort 2 (n = 478). TTSP ≥36 months was achieved in 64.5% of patients overall, 59.5% of patients in Cohort 1, and 66.4% of patients in Cohort 2. Median overall survival from classification as RAI-R was 167 months and median progression-free survival from start of MKI therapy was 19.2 months and from start of sorafenib therapy 16.7 months. Among sorafenib-treated patients, 70% had dose modifications, 35% had a dose reduction, 89% experienced ≥1 treatment-emergent adverse event (TEAE), and 82% experienced ≥1 drug-related TEAE. Conclusions: This real-world study provides valuable insight into outcomes in patients with asymptomatic, progressive RAI-R DTC under observation or receiving MKI treatment. TTSP in the FAS provides insight into the current prognosis for patients with RAI-R DTC in the era of MKIs. Registration: NCT02303444.