Secukinumab provided significant and sustained improvement in the signs and symptoms of ankylosing spondylitis: results from the 52-week,Phase III China-centric study,MEASURE 5

BackgroundSecukinumab demonstrated sustained efficacy in patients with ankylosing spondylitis (AS) through 5 years in pivotal Phase III studies. Here, we present efficacy and safety results (52-week) of secukinumab in patients with AS from the MEASURE 5 study.MethodsMEASURE 5 was a 52-week, Phase III, China-centric study. Eligible patients were randomly assigned (2:1) to receive subcutaneous secukinumab 150 mg or placebo weekly for the first five doses and then once every 4 weeks (q4w). All placebo patients switched to secukinumab 150 mg q4w starting at Week 16. Primary endpoint was Assessments of SpondyloArthritis international Society (ASAS) 20 at Week 16. Randomization was stratified by region (China vs. non-China).ResultsOf 458 patients (secukinumab 150 mg, N = 305; placebo, N = 153) randomized, 327 (71.4%) were from China and 131 (28.6%) were not from China. Of these, 97.7% and 97.4% patients completed Week 16 and 91.1% and 95.3% (placebo-secukinumab) patients completed Week 52 of treatment. The primary endpoint was met; secukinumab significantly improved ASAS20 response at Week 16 vs. placebo (58.4% vs. 36.6%; P < 0.0001); corresponding rate in the Chinese population was 56.0% vs. 38.5% (P < 0.01). All secondary efficacy endpoints significantly improved with secukinumab 150 mg in the overall population at Week 16; responses were maintained with a trend toward increased efficacy from Week 16 to 52. No new or unexpected safety signals were reported up to Week 52.ConclusionsSecukinumab 150 mg demonstrated rapid and significant improvement in signs and symptoms of AS. Secukinumab was well tolerated and the safety profile was consistent with previous reports. Efficacy and safety results were comparable between the overall and Chinese populations.Trial registrationClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT02896127","term_id":"NCT02896127"}}NCT02896127; https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT02896127","term_id":"NCT02896127"}}NCT02896127?term={"type":"clinical-trial","attrs":{"text":"NCT02896127","term_id":"NCT02896127"}}NCT02896127&draw=2&rank=1.     

Predicting fetal weight by three-dimensional limb volume ultrasound (AVol/TVol) and abdominal circumference

Background:Fetal weight is an important parameter to ensure maternal and child safety. The purpose of this study was to use three-dimensional (3D) limb volume ultrasound combined with fetal abdominal circumference (AC) measurement to establish a model to predict fetal weight and evaluate its efficiency.Methods:A total of 211 participants with single pregnancy (28–42 weeks) were selected between September 2017 and December 2018 in the Beijing Obstetrics and Gynecology Hospital of Capital Medical University. The upper arm (AVol)/thigh volume (TVol) of fetuses was measured by the 3D limb volume technique. Fetal AC was measured by two-dimensional ultrasound. Nine cases were excluded due to incomplete information or the interval between examination and delivery >7 days. The enrolled 202 participants were divided into a model group (134 cases, 70%) and a verification group (68 cases, 30%) by mechanical sampling method. The linear relationship between limb volume and fetal weight was evaluated using Pearson Chi-squared test. The prediction model formula was established by multivariate regression with data from the model group. Accuracy of the model formula was evaluated with verification group data and compared with traditional formulas (Hadlock, Lee2009, and INTERGROWTH-21^st) by paired t-test and residual analysis. Receiver operating characteristic curves were generated to predict macrosomia.Results:AC, AVol, and TVol were linearly related to fetal weight. Pearson correlation coefficient was 0.866, 0.862, and 0.910, respectively. The prediction model based on AVol/TVol and AC was established as follows: Y = −481.965 + 12.194TVol + 15.358AVol + 67.998AC, R²_adj = 0.868. The scatter plot showed that when birth weight fluctuated by 5% (i.e., 95% to 105%), the difference between the predicted fetal weight by the model and the actual weight was small. A paired t-test showed that there was no significant difference between the predicted fetal weight and the actual birth weight (t = −1.015, P = 0.314). Moreover, the residual analysis showed that the model formula''s prediction efficiency was better than the traditional formulas with a mean residual of 35,360.170. The combined model of AVol/TVol and AC was superior to the Lee2009 and INTERGROWTH-21^st formulas in the diagnosis of macrosomia. Its predictive sensitivity and specificity were 87.5% and 91.7%, respectively.Conclusion:Fetal weight prediction model established by semi-automatic 3D limb volume combined with AC is of high accuracy, sensitivity, and specificity. The prediction model formula shows higher predictive efficiency, especially for the diagnosis of macrosomia.Trial Registration:ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT03002246","term_id":"NCT03002246"}}NCT03002246; https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT03002246","term_id":"NCT03002246"}}NCT03002246?recrs=e&cond=fetal&draw=8&rank=67.     

Epidemiological and clinical features of functional dyspepsia in a region with a high incidence of esophageal cancer in China

Background:Functional dyspepsia (FD) has rarely been investigated in areas with a high prevalence of esophageal squamous cell carcinoma (ESCC). This study aims to reveal the epidemiological and clinical features of FD and organic dyspepsia (OD) in such a population.Methods:A middle-aged and elderly population-based study was conducted in a region with a high incidence of ESCC. All participants completed the Gastroesophageal Reflux Disease Questionnaire and Functional Gastrointestinal Disease Rome III Diagnostic Questionnaire, and they underwent gastroscopy. After exclusion of gastroesophageal reflux disease, uninvestigated dyspepsia (UID) was divided into OD and FD for further analyses.Results:A total of 2916 participants were enrolled from July 2013 to March 2014 in China. We detected 166 UID cases with questionnaires, in which 17 patients with OD and 149 with FD were diagnosed via gastroscopy. OD cases presented as reflux esophagitis (RE), ESCC, and duodenal ulcer. Heartburn (52.94%) and reflux (29.41%) were common in OD, but no symptomatic differences were found between FD and OD. Male sex, low education level, and liquid food were the risk factors for OD, while frequent fresh vegetable consumption was a protective factor. FD included 56 (37.58%) cases of postprandial distress syndrome (PDS), 52 (34.89%) of epigastric pain syndrome (EPS), nine (6.04%) of PDS + EPS, and 32 (21.48%) of FD + functional esophageal disorders. The Helicobacter pylori infection rate in FD patients was not higher than that in the control group (34.23% vs. 42.26%, P = 0.240). Frequent spicy food consumption was associated with PDS (odds ratio [OR]: 2.088, 95% confidence interval [CI]: 1.028–4.243), while consumption of deep well water was protective for PDS (OR: 0.431, 95% CI: 0.251–0.741).Conclusions:The prevalence of FD was 5.11% in the studied population. Gastroscopy should be prescribed for dyspepsia patients in case that ESCC and RE would be missed in UID cases diagnosed solely by the Rome III questionnaire.Trial Registration:ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT01688908","term_id":"NCT01688908"}}NCT01688908; https://clinicaltrials.gov/ct2/show/record/{"type":"clinical-trial","attrs":{"text":"NCT01688908","term_id":"NCT01688908"}}NCT01688908.     

Neural control of pressure support ventilation improved patient-ventilator synchrony in patients with different respiratory system mechanical properties: a prospective,crossover trial

BackgroundConventional pressure support ventilation (PS_P) is triggered and cycled off by pneumatic signals such as flow. Patient-ventilator asynchrony is common during pressure support ventilation, thereby contributing to an increased inspiratory effort. Using diaphragm electrical activity, neurally controlled pressure support (PS_N) could hypothetically eliminate the asynchrony and reduce inspiratory effort. The purpose of this study was to compare the differences between PS_N and PS_P in terms of patient-ventilator synchrony, inspiratory effort, and breathing pattern.MethodsEight post-operative patients without respiratory system comorbidity, eight patients with acute respiratory distress syndrome (ARDS) and obvious restrictive acute respiratory failure (ARF), and eight patients with chronic obstructive pulmonary disease (COPD) and mixed restrictive and obstructive ARF were enrolled. Patient-ventilator interactions were analyzed with macro asynchronies (ineffective, double, and auto triggering), micro asynchronies (inspiratory trigger delay, premature, and late cycling), and the total asynchrony index (AI). Inspiratory efforts for triggering and total inspiration were analyzed.ResultsTotal AI of PS_N was consistently lower than that of PS_P in COPD (3% vs. 93%, P = 0.012 for 100% support level; 8% vs. 104%, P = 0.012 for 150% support level), ARDS (8% vs. 29%, P = 0.012 for 100% support level; 16% vs. 41%, P = 0.017 for 150% support level), and post-operative patients (21% vs. 35%, P = 0.012 for 100% support level; 15% vs. 50%, P = 0.017 for 150% support level). Improved support levels from 100% to 150% statistically increased total AI during PS_P but not during PS_N in patients with COPD or ARDS. Patients’ inspiratory efforts for triggering and total inspiration were significantly lower during PS_N than during PS_P in patients with COPD or ARDS under both support levels (P < 0.05). There was no difference in breathing patterns between PS_N and PS_P.ConclusionsPS_N improves patient-ventilator synchrony and generates a respiratory pattern similar to PS_P independently of any level of support in patients with different respiratory system mechanical properties. PS_N, which reduces the trigger and total patient''s inspiratory effort in patients with COPD or ARDS, might be an alternative mode for PS_P.Trial RegistrationClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT01979627","term_id":"NCT01979627"}}NCT01979627; https://clinicaltrials.gov/ct2/show/record/{"type":"clinical-trial","attrs":{"text":"NCT01979627","term_id":"NCT01979627"}}NCT01979627.     

Haploidentical transplantation has a superior graft-versus-leukemia effect than HLA-matched sibling transplantation for Ph– high-risk B-cell acute lymphoblastic leukemia

Background:Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph–) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph– high-risk B-ALL.Methods:This study population came from two prospective multicenter trials ({"type":"clinical-trial","attrs":{"text":"NCT01883180","term_id":"NCT01883180"}}NCT01883180, {"type":"clinical-trial","attrs":{"text":"NCT02673008","term_id":"NCT02673008"}}NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.Results:A total of 335 patients with Ph– high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%–34.7%) and 42.6% (35.5%–49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups (P = 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%–25.4%) and 25.9% (19.9%–32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%–74.4%) and 61.6% (54.2%–68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%–70.7%) and 58.2% (50.8%–64.9%; P = 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%–59.5%) and 37.8% (30.9%–44.6%; P = 0.041), respectively, in the HID and MSD groups.Conclusion:HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph– high-risk B-ALL patients.Trial registration:ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01883180","term_id":"NCT01883180"}}NCT01883180, {"type":"clinical-trial","attrs":{"text":"NCT02673008","term_id":"NCT02673008"}}NCT02673008.     

Short-term combined treatment with exenatide and metformin for overweight/obese women with polycystic ovary syndrome

Background:Obesity and insulin resistance (IR) are common features of polycystic ovary syndrome (PCOS). Metformin (MET) increases insulin sensitivity, but it is associated with unsatisfactory weight loss. The glucagon-like peptide-1 receptor agonist exenatide has been shown to reduce weight and IR in patients with diabetes. This study aimed to explore the therapeutic effects of exenatide once-weekly (QW) combined with MET on body weight, as well as metabolic and endocrinological parameters in overweight/obese women with PCOS.Methods:Fifty overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomized to one of two treatment groups: MET (500 mg three times a day [TID]) or combination treatment (COM) (MET 500 mg TID, exenatide 2 mg QW) for 12 weeks. The primary outcomes were anthropometric changes associated with obesity, and the secondary outcomes included changes in reproductive hormone levels, glucose and lipid metabolism, and C-reactive protein.Results:Forty (80%) patients completed the study. COM therapy was superior to MET monotherapy in reducing weight (P = 0.045), body mass index (BMI) (P = 0.041), and waist circumference (P = 0.023). Patients in the COM group on an average lost 3.8 ± 2.4 kg compared with 2.1 ± 3.0 kg in the MET group. In the COM group, BMI and waist circumference decreased by 1.4 ± 0.87 kg/m² and 4.63 ± 4.42 cm compared with 0.77 ± 1.17 kg/m² and 1.72 ± 3.07 cm in the MET group, respectively. Moreover, levels of fasting glucose, oral glucose tolerance test (OGTT) 2-h glucose, and OGTT 2-h insulin were significantly lower with COM therapy than with MET (P < 0.050). Mild and moderate gastrointestinal reactions were the most common adverse events in both groups.Conclusions:COM therapy was more effective than MET alone in reducing body weight, BMI, and waist circumference, and improving insulin sensitivity in overweight/obese women with PCOS, with acceptable short-term side effects.Trial registration:ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT04029272","term_id":"NCT04029272"}}NCT04029272. https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT04029272","term_id":"NCT04029272"}}NCT04029272     

Comparison of sequential feeding and continuous feeding on the blood glucose of critically ill patients: a non-inferiority randomized controlled trial

Background:Glucose control is an important aspect in managing critically ill patients. The goal of this study was to compare the effects of sequential feeding (SF) and continuous feeding (CF) on the blood glucose of critically ill patients.Methods:A non-inferiority randomized controlled trial was adopted in this study. A total of 62 patients who were fed enteral nutritional suspension through gastric tubes were enrolled. After achieving 80% of the nutrition target calories (25 kcal·kg⁻¹·day⁻¹) through CF, the patients were then randomly assigned into SF and CF groups. In the SF group, the feeding/fasting time was reasonably determined according to the circadian rhythm of the human body as laid out in traditional Chinese medicine theory. The total daily dosage of the enteral nutritional suspension was equally distributed among three time periods of 7 to 9 o’clock, 11 to 13 o’clock, and 17 to 19 o’clock. The enteral nutritional suspension in each time period was pumped at a uniform rate within 2 h by an enteral feeding pump. In the CF group, patients received CF at a constant velocity by an enteral feeding pump throughout the study. Blood glucose values at five points (6:00/11:00/15:00/21:00/1:00) were monitored and recorded for seven consecutive days after randomization. Enteral feeding intolerance was also recorded. Non-inferiority testing was adopted in this study, the chi-square test or Fisher test was used for qualitative data, and the Mann-Whitney U test was used for quantitative data to determine differences between groups. In particular, a repeated measure one-way analysis of variance was used to identify whether changes in glucose value variables across the time points were different between the two groups.Results:There were no significant demographic or physiological differences between the SF and CF groups (P > 0.050). The average glucose level in SF was not higher than that in CF (8.8 [7.3–10.3] vs. 10.7 [9.1–12.1] mmol/L, Z = −2.079, P for non-inferiority = 0.019). Hyperglycemia incidence of each patient was more common in the CF group than that in the SF group (38.4 [19.1–63.7]% vs. 11.8 [3.0–36.7]%, Z = −2.213, P = 0.027). Hypoglycemia was not found in either group. Moreover, there was no significant difference during the 7 days in the incidence of feeding intolerance (P > 0.050).Conclusions:In this non-inferiority study, the average blood glucose in SF was not inferior to that in CF. The feeding intolerance in SF was similar to that in CF. SF may be as safe as CF for critically ill patients.Trial RegistrationClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT03439618","term_id":"NCT03439618"}}NCT03439618; https://clinicaltrials.gov/ct2/show/record/{"type":"clinical-trial","attrs":{"text":"NCT03439618","term_id":"NCT03439618"}}NCT03439618     

A 14-year multi-institutional collaborative study of Chinese pelvic floor surgical procedures related to pelvic organ prolapse

Background:It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011.Methods:A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided).Results:The number of different procedures during October 1, 2011−September 30, 2018 was more than twice that during October 1, 2004−September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004–September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011–September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107).Conclusions:The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly.Trial registration number:{"type":"clinical-trial","attrs":{"text":"NCT03620565","term_id":"NCT03620565"}}NCT03620565, https://register.clinicaltrials.gov.     

Efficacy and safety of human chorionic gonadotropin combined with human menopausal gonadotropin and a gonadotropin-releasing hormone pump for male adolescents with congenital hypogonadotropic hypogonadism

Background:Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH.Methods:Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0–3 months) and a follow-up phase (3–12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance).Results:Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ± 2.3 mL and 4.1 ± 1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t = 1.394). The PL reached 6.9 ± 1.8 cm and 5.1 ± 1.6 cm (P < 0.05, t = 3.083), the PD reached 2.4 ± 0.5 cm and 2.0 ± 0.6 cm (P < 0.05, t = 2.224), respectively, in the two groups. At the end of 6 months of treatment, biomarkers were in normal range in the two groups. Compared with the GnRH group, the testosterone (T) level and growth of PL and PD were significantly greater in the hCG/hMG group (all P < 0.05). While the TV of both groups increased, the difference was not statistically significant (P > 0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference.Conclusions:The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research.Trial Registration:ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.     

Hepatitis B core-related antigen reflects viral replication and protein production in chronic hepatitis B patients

Background:Hepatitis B core-related antigen (HBcrAg) is a promising disease-monitoring marker for chronic hepatitis B (CHB). We investigated correlations between HBcrAg with antiviral efficacy and virological and histological variables.Methods:One hundred and forty-five CHB patients from the mainland of China between August 2013 and September 2016 who underwent liver biopsy received entecavir therapy and had paired liver biopsy at 78 weeks. We analyzed correlations between HBcrAg and virological and histological variables in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. We also explored the predictors of HBeAg loss after 78 weeks of antiviral therapy. Pearson correlation analysis and logistic forward stepwise regression were the main statistic methods.Results:HBeAg-positive patients (n = 93) had higher baseline HBcrAg (median 7.4 vs. 5.3 log₁₀ U/mL P < 0.001) and greater HBcrAg declines (median 1.6 vs. 0.9 log₁₀ U/mL P = 0.007) than HBeAg-negative patients after 78 weeks of therapy. At baseline, HBcrAg correlated with hepatitis B virus (HBV) DNA in both HBeAg-positive (r = 0.641, P < 0.001) and -negative patients (r = 0.616, P < 0.001), with hepatitis B surface antigen (HBsAg) in HBeAg-positive patients (r = 0.495, P < 0.001), but not with anti-hepatitis B virus core antibody (anti-HBc). Weak correlations existed between HBcrAg, histology activity index (HAI; r = 0.232, P = 0.025), and Ishak fibrosis score (r = −0.292, P = 0.005) in HBeAg-positive patients. At 78 weeks, significant correlations existed only between HBcrAg and anti-HBc in HBeAg-positive (r = −0.263, P = 0.014) and HBeAg-negative patients (r = −0.291, P = 0.045). Decreased HBcrAg significantly correlated with reduced HBV DNA (r = 0.366, P = 0.001; r = 0.626, P < 0.001) and HBsAg (r = 0.526, P = 0.001; r = 0.289, P = 0.044) in HBeAg-positive and -negative patients, respectively, and with reduced HAI in HBeAg-positive patients (r = 0.329, P = 0.001). Patients with HBeAg loss (n = 29) showed a larger reduction in HBcrAg than those without (median 2.3 vs. 1.3 log₁₀ U/mL, P = 0.001). In multivariate analysis, decreased HBcrAg was an independent predictor of HBeAg loss (P = 0.005).Conclusions:HBcrAg reflects viral replication and protein production. Decreased HBcrAg could predict HBeAg loss after antiviral therapy.Trial registration:Clinical Trials.gov: NCT01962155; https://www.clinicaltrials.gov/ct2/show/NCT01962155?term=NCT01962155&draw=2&rank=1     

Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter,open-label,single-arm,phase 3 study

Background:Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment.Methods:This was a prospective, multicenter, open-label, single-arm, phase 3 study ({"type":"clinical-trial","attrs":{"text":"NCT01596621","term_id":"NCT01596621"}}NCT01596621; {"type":"entrez-nucleotide","attrs":{"text":"C18083","term_id":"1579685"}}C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m² infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR.Results:A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%–81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities.Conclusion:Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients.Clinical trial registration:ClinicalTrials.gov, No. {"type":"clinical-trial","attrs":{"text":"NCT01596621","term_id":"NCT01596621"}}NCT01596621; https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT01596621","term_id":"NCT01596621"}}NCT01596621     

Functional mitral regurgitation combined with increased early diastolic transmitral velocity to early mitral annulus diastolic velocity ratio is associated with a poor prognosis in patients with shock

Background:Functional mitral regurgitation (FMR) is common in critically ill patients and may cause left atrial (LA) pressure elevation. This study aims to explore the prognostic impact of synergistic LA pressure elevation and FMR in patients with shock.Methods:We retrospectively screened 130 consecutive patients of 175 patients with shock from April 2016 to June 2017. The incidence and impact of FMR and early diastolic transmitral velocity to early mitral annulus diastolic velocity ratio (E/e’) ≥ 4 within 6 h of shock on the prognosis of patients were evaluated. Finally, the synergistic effect of FMR and E/e’ were assessed by combination, grouping, and trend analyses.Results:Forty-four patients (33.8%) had FMR, and 15 patients (11.5%) had E/e’ elevation. A multivariate analysis revealed FMR and E/e’ as independent correlated factors for 28-day mortality (P = 0.043 and 0.028, respectively). The Kaplan-Meier survival analysis revealed a significant difference in survival between patients with and without FMR (χ² = 7.672, P = 0.006) and between the E/e’ ≥ 14 and E/e’ < 14 groups (χ² = 19.351, P < 0.010). Twenty-eight-day mortality was significantly different among the four groups (χ² = 30.141, P < 0.010). The risk of 28-day mortality was significantly higher in group 4 (E/e’ ≥ 14 with FMR) compared with groups 1 (E/e’ < 14 without FMR) and 2 (E/e’ < 14 with FMR) (P = 0.001 and 0.046, respectively).Conclusions:Patients with shock can be identified by the presence of FMR. FMR and E/e’ are independent risk factors for a poor prognosis in these patients, and prognosis is worst when FMR and E/e’ ≥ 14 are present. It may be possible to improve prognosis by reducing LA pressure and E/e’.Trial Registration:ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT03082326","term_id":"NCT03082326"}}NCT03082326.     

Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized,controlled, phase 3, non-inferiority TALENT study

BackgroundAlbuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.MethodsWe carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%.ResultsAt the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.ConclusionsThe TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.Trial registrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02369965","term_id":"NCT02369965"}}NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx     

Evaluation of electronic health record-integrated digital health tools to engage hospitalized patients in discharge preparation

ObjectiveTo evaluate the effect of electronic health record (EHR)-integrated digital health tools comprised of a checklist and video on transitions-of-care outcomes for patients preparing for discharge.Materials and MethodsEnglish-speaking, general medicine patients (>18 years) hospitalized at least 24 hours at an academic medical center in Boston, MA were enrolled before and after implementation. A structured checklist and video were administered on a mobile device via a patient portal or web-based survey at least 24 hours prior to anticipated discharge. Checklist responses were available for clinicians to review in real time via an EHR-integrated safety dashboard. The primary outcome was patient activation at discharge assessed by patient activation (PAM)-13. Secondary outcomes included postdischarge patient activation, hospital operational metrics, healthcare resource utilization assessed by 30-day follow-up calls and administrative data and change in patient activation from discharge to 30 days postdischarge.ResultsOf 673 patients approached, 484 (71.9%) enrolled. The proportion of activated patients (PAM level 3 or 4) at discharge was nonsignificantly higher for the 234 postimplementation compared with the 245 preimplementation participants (59.8% vs 56.7%, adjusted OR 1.23 [0.38, 3.96], P = .73). Postimplementation participants reported 3.75 (3.02) concerns via the checklist. Mean length of stay was significantly higher for postimplementation compared with preimplementation participants (10.13 vs 6.21, P < .01). While there was no effect on postdischarge outcomes, there was a nonsignificant decrease in change in patient activation within participants from pre- to postimplementation (adjusted difference-in-difference of −16.1% (9.6), P = .09).ConclusionsEHR-integrated digital health tools to prepare patients for discharge did not significantly increase patient activation and was associated with a longer length of stay. While issues uncovered by the checklist may have encouraged patients to inquire about their discharge preparedness, other factors associated with patient activation and length of stay may explain our observations. We offer insights for using PAM-13 in context of real-world health-IT implementations.Trial RegistrationNIH US National Library of Medicine, {"type":"clinical-trial","attrs":{"text":"NCT03116074","term_id":"NCT03116074"}}NCT03116074, clinicaltrials.gov     

Comparable efficacy of 100 mg aspirin twice daily and rivaroxaban for venous thromboembolism prophylaxis following primary total hip arthroplasty: a randomized controlled trial

Background:Aspirin has demonstrated safety and efficacy for venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA); however, inconsistent dose regimens have been reported in the literature. This study aimed to evaluate and compare the safety and efficacy of 100 mg aspirin twice daily with rivaroxaban in VTE prophylaxis following THA.Methods:Patients undergoing elective unilateral primary THA between January 2019 and January 2020 were prospectively enrolled in the study and randomly allocated to receive 5 weeks of VTE prophylaxis with either oral enteric-coated aspirin (100 mg twice daily) or rivaroxaban (10 mg once daily). Medication safety and efficacy were comprehensively evaluated through symptomatic VTE incidence, deep vein thrombosis (DVT) on Doppler ultrasonography, total blood loss (TBL), laboratory bloodwork, Harris hip score (HHS), post-operative recovery, and the incidence of other complications.Results:We included 70 patients in this study; 34 and 36 were allocated to receive aspirin and rivaroxaban prophylaxis, respectively. No cases of symptomatic VTE occurred in this study. The DVT rate on Doppler ultrasonography in the aspirin group was not significantly different from that in the rivaroxaban group (8.8% vs. 8.3%, χ² = 0.01, P = 0.91), confirming the non-inferiority of aspirin for DVT prophylaxis (χ² = 2.29, P = 0.01). The calculated TBL in the aspirin group (944.9 mL [658.5–1137.8 mL]) was similar to that in the rivaroxaban group (978.3 mL [747.4–1740.6mL]) (χ² = 1.55, P = 0.12). However, there were no significant inter-group differences in HHS at post-operative day (POD) 30 (Aspirin: 81.0 [78.8–83.0], Rivaroxaban: 81.0 [79.3–83.0], χ² = 0.43, P = 0.67) and POD 90 (Aspirin: 90.0 [89.0–92.0], Rivaroxaban: 91.5 [88.3–92.8], χ² = 0.77, P = 0.44), the incidence of bleeding events (2.9% vs. 8.3%, χ² = 0.96, P = 0.33), or gastrointestinal complications (2.9% vs. 5.6%, χ² = 1.13, P = 0.29).Conclusion:In terms of safety and efficacy, the prophylactic use of 100 mg aspirin twice daily was not statistically different from that of rivaroxaban in preventing VTE and reducing the risk of blood loss following elective primary THA. This supports the use of aspirin chemoprophylaxis following THA as a less expensive and more widely available option for future THAs.Trial Registration:Chictr.org, ChiCTR18000202894; http://www.chictr.org.cn/showproj.aspx?proj=33284     

Safety and efficacy of allogeneic natural killer cell immunotherapy on human immunodeficiency virus type 1 immunological non-responders: a brief report

Background:Allogeneic natural killer (NK) cell immunotherapy is recognized as a promising anti-tumor strategy, but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1 (HIV-1) infected patients is unknown. This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders (INRs) receiving antiretroviral therapy (ART).Methods:From February to April 2018, a prospective, randomized, controlled, open-label clinical trial, which enrolled 20 HIV-1 INRs following specific inclusion criteria, was conducted at Nankai University Second People''s Hospital. Participants were randomly allocated (simple randomization 1:1) to either the combined treatment (NK + ART) group (n = 10) or the control (ART) group (n = 10). The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen (HLA)-Cw mismatched healthy donor were prepared (10⁸ cells in each injection) and intravenously infused to each recruited patient of NK+ART group in three courses. Key immune parameters (CD4 count, CD8 count, CD4/CD8 ratio), laboratory tests (count of blood cells, biochemistry panel) and symptoms at baseline and at month 1, 3, 6, 9, 12, and 24 were measured/collected to analyze the safety and efficacy of the therapy. Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance (ANOVA) test. Generalized estimating equations (GEE) model was performed to evaluate the overall effect of the NK+ART group vs. the ART group.Results:From baseline to 24 months, we noted a mean CD4 count augmentation (139 to 243 cells/μL) in the NK + ART group and (144 to 176 cells/μL) in the ART group (difference, 67; 95% CI, 10 to 124; P = 0.024). Our estimations revealed that NK+ART group could improve CD4 level (β = 54.59, P = 0.006) and CD8 level (β = 322.47, P = 0.010) on average among the six measurements compared with the ART group. Only two (2/10, 20%) participants in the NK+ART group developed a transient mild fever after the first course.Conclusions:This preliminary study informs that HIV-1 INRs, allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio. The practical effects, however, need long-term follow-up observations. Further study on the potential underlying mechanism is warranted.Registration info:www.chictr.org.cn/showproj.aspx?proj=34912 (No. ChiCTR1900020634).     

Celecoxib as an adjuvant to chemotherapy for patients with metastatic colorectal cancer: A randomized controlled clinical study

Objectives:To investigate the anti-tumor activity and tolerability of celecoxib as an adjuvant therapy for patients with metastatic colorectal cancer (CRC).Methods:In this randomized controlled study, 54 patients with metastatic CRC were randomized into 2 groups; the control group (n=28) which received 6 cycles of folinic acid, fluorouracil and irinotecan (FOLFIRI) regimen (5-flourouracil, leucovorin, irinotecan), and the celecoxib group (n=26) which received 6 cycles of FOLFIRI regimen plus celecoxib 200 mg twice daily. The study duration was 3 months. Patients were assessed at baseline and at the end of intervention through the Response Evaluation Criteria in Solid Tumors objective response rate (ORR) and through evaluating the serum concentrations of vascular endothelial growth factor (VEGF), soluble factor-related apoptosis (sFAS), sFAS ligand (sFASL), and epithelial neutrophil-activating peptide -78 (ENA-78/CXCL5). Common Terminology Criteria for Adverse Events version 6.0 was used for evaluating drug-related toxicity.Results:After intervention, celecoxib/FOLFIRI arm showed significant elevation in ORR as compared to FOLFIRI arm (p=0.001). As compared to FOLFIRI arm, celecoxib/FOLFIRI arm showed significantly lower VEGF (p<0.001), CXCL5 (p<0.001), and sFASL (p<0.001) serum levels and significantly higher sFAS serum level and sFAS/FASL ratio (p<0.001). Furthermore, celecoxib/FOLFIRI arm showed significantly higher progression-free survival and one-year overall survival when compared to FOLFIRI arm.Conclusion:Celecoxib plus chemotherapy may represent an effective and safe synergetic protocol for patients with metastatic CRC. Clinicaltrial.gov ID:{"type":"clinical-trial","attrs":{"text":"NCT03645187","term_id":"NCT03645187"}}NCT03645187     

Dietary advice and oral nutritional supplements do not increase survival in older malnourished adults: a multicentre randomised controlled trial

Objectives: The study aimed to investigate the effect on survival after 6 months of treatment involving individual dietary advice and oral nutritional supplements in older malnourished adults after discharge from hospital.Methods: This multicentre randomised controlled trial included 671 patients aged 65 years who were malnourished or at risk of malnutrition when admitted to hospital between 2010 and 2014, and followed up after 8.2 years (median 4.1 years). Patients were randomised to receive dietary advice or oral nutritional supplements, separate or in combination, or routine care. The intervention started at discharge from the hospital and continued for 6 months, with survival being the main outcome measure.Results: During the follow-up period 398 (59.3%) participants died. At follow-up, the survival rates were 36.9% for dietary advice, 42.4% for oral nutritional supplements, 40.2% for dietary advice combined with oral nutritional supplements, and 43.3% for the control group (log-rank test p = 0.762). After stratifying the participants according to nutritional status, survival still did not differ significantly between the treatment arms (log-rank test p = 0.480 and p = 0.298 for the 506 participants at risk of malnutrition and the 165 malnourished participants, respectively).Conclusions: Oral nutritional supplements with or without dietary advice, or dietary advice alone, do not improve the survival of malnourished older adults. These results do not support the routine use of supplements in older malnourished adults, provided that survival is the aim of the treatment.Trial registration: ClinicalTrials.gov with ID: {"type":"clinical-trial","attrs":{"text":"NCT01057914","term_id":"NCT01057914"}}NCT01057914     

A double-blind,double-dummy,randomized controlled,multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis

Background:Clinical observational studies revealed that ⁹⁹Tc-methylene diphosphonate (⁹⁹Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of ⁹⁹Tc-MDP plus methotrexate (MTX) vs. MTX alone or ⁹⁹Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA.Methods:Eligible patients with moderate to severely active RA were randomized to receive ⁹⁹Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or ⁹⁹Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48.Results:At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + ⁹⁹Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or ⁹⁹Tc-MDP group (47.5%) (P = 0.03 for MTX + ⁹⁹Tc-MDP vs. MTX, and MTX + ⁹⁹Tc-MDP vs.⁹⁹Tc-MDP, respectively). The participants in the MTX + ⁹⁹Tc-MDP group and the ⁹⁹Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + ⁹⁹Tc-MDP vs. MTX: P = 0.03, ⁹⁹Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed.Conclusions:This study demonstrated that the combination of ⁹⁹Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and ⁹⁹Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of ⁹⁹Tc-MDP therapy in patients with RA are warranted.Trial Registration:Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.     

Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized,double-blind,and placebo-controlled phase 1 and phase 2 clinical trials

Background:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.Methods:Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.Results:In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.Conclusions:Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.Trial Registration:http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).