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.     

Comparison of two vasopressor protocols for preventing hypotension post-spinal anesthesia during cesarean section: a randomized controlled trial

Background:Norepinephrine infusion decreases hypotension after spinal anesthesia during cesarean section. This study aimed to compare the efficacy of norepinephrine infusion and ephedrine bolus against post-spinal hypotension in parturients.Methods:In this double-blinded, randomized controlled clinical trial, parturients scheduled for elective cesarean section were randomly allocated to receive norepinephrine infusion (0.05 μg·kg⁻¹·min⁻¹) just before spinal anesthesia continuing for 30 min or ephedrine bolus (0.15 mg/kg) just before spinal anesthesia. A rescue bolus (5 μg norepinephrine for the norepinephrine group, and 5 mg ephedrine for the ephedrine group) was administered whenever hypotension occurred. Our primary outcome was the incidence of hypotension within 30 min of spinal anesthesia administration. Secondary outcomes included maternal and neonatal outcomes 30 min after spinal block, and neonatal cerebral oxygenation 10 min after birth.Results:In total, 190 patients were enrolled; of these patients, 177 were included in the final analysis. Fewer patients suffered hypotension in the norepinephrine group than in the ephedrine group (29.5% vs. 44.9%, odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.28–0.95, P = 0.034). Moreover, the tachycardia frequency was lower in the norepinephrine group than in the ephedrine group (OR: 0.22, 95% CI: 0.11–0.44, P < 0.001), and patients suffered less nausea and vomiting (OR: 0.28, 95% CI: 0.11–0.70, P = 0.004). There was no difference in Apgar scores and umbilical arterial blood gas analysis between the two groups. However, neonatal cerebral regional saturations were significantly higher after birth in the norepinephrine group than in the ephedrine group (mean difference: 2.0%, 95% CI: 0.55%–3.45%, P = 0.008).Conclusion:In patients undergoing elective cesarean section with spinal anesthesia, norepinephrine infusion compared to ephedrine bolus resulted in less hypotension and tachycardia, and exhibited potential neonatal benefits.Trial Registration:ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT02542748","term_id":"NCT02542748"}}NCT02542748; https://clinicaltrials.gov/ct2/show/record/{"type":"clinical-trial","attrs":{"text":"NCT02542748","term_id":"NCT02542748"}}NCT02542748     

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.     

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.     

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.     

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     

Adaptive learning algorithms to optimize mobile applications for behavioral health: guidelines for design decisions

ObjectiveProviding behavioral health interventions via smartphones allows these interventions to be adapted to the changing behavior, preferences, and needs of individuals. This can be achieved through reinforcement learning (RL), a sub-area of machine learning. However, many challenges could affect the effectiveness of these algorithms in the real world. We provide guidelines for decision-making.Materials and MethodsUsing thematic analysis, we describe challenges, considerations, and solutions for algorithm design decisions in a collaboration between health services researchers, clinicians, and data scientists. We use the design process of an RL algorithm for a mobile health study “DIAMANTE” for increasing physical activity in underserved patients with diabetes and depression. Over the 1.5-year project, we kept track of the research process using collaborative cloud Google Documents, Whatsapp messenger, and video teleconferencing. We discussed, categorized, and coded critical challenges. We grouped challenges to create thematic topic process domains.ResultsNine challenges emerged, which we divided into 3 major themes: 1. Choosing the model for decision-making, including appropriate contextual and reward variables; 2. Data handling/collection, such as how to deal with missing or incorrect data in real-time; 3. Weighing the algorithm performance vs effectiveness/implementation in real-world settings.ConclusionThe creation of effective behavioral health interventions does not depend only on final algorithm performance. Many decisions in the real world are necessary to formulate the design of problem parameters to which an algorithm is applied. Researchers must document and evaulate these considerations and decisions before and during the intervention period, to increase transparency, accountability, and reproducibility.Trial Registrationclinicaltrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT03490253","term_id":"NCT03490253"}}NCT03490253.     

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 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 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     

Expression profile of circular RNAs in epicardial adipose tissue in heart failure

BackgroundRecent studies have reported circular RNA (circRNA) expression profiles in various tissue types; however, circRNA expression profile in human epicardial adipose tissue (EAT) remains undefined. This work aimed to compare circRNA expression patterns in EAT between the heart failure (HF) and non-HF groups.MethodsRNA-sequencing was carried out to compare circRNA expression patterns in EAT specimens from coronary artery disease cases between the HF and non-HF groups. Quantitative real-time polymerase chain reaction was performed for validation. Comparisons of patient characteristics between the two groups were using t test, Mann-Whitney U test, and Chi-squared test.ResultsA total of 141 circRNAs substantially different between the HF and non-HF groups (P < 0.05; fold change >2) were detected, including 56 up-regulated and 85 down-regulated. Among them, hsa_circ_0005565 stood out, for it had the highest fold change and was significantly increased in HF patients in quantitative real-time polymerase chain reaction validation. The top highly expressed EAT circRNAs corresponded to genes involved in cell proliferation and inflammatory response, including {"type":"entrez-geo","attrs":{"text":"GSE1","term_id":"1"}}GSE1, RHOBTB3, HIPK3, UBXN7, PCMTD1, N4BP2L2, CFLAR, EPB41L2, FCHO2, FNDC3B, and SPECC1. The top enriched Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway were positive regulation of metabolic processes and insulin resistance, respectively.ConclusionThese data indicate EAT circRNAs may contribute to the pathogenesis of metabolic disorders causing HF.     

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).     

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     

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.     

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     

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     

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.     

Impact of event notification services on timely follow-up and rehospitalization among primary care patients at two Veterans Affairs Medical Centers

ObjectiveTo examine the effectiveness of event notification service (ENS) alerts on health care delivery processes and outcomes for older adults.Materials and methodsWe deployed ENS alerts in 2 Veterans Affairs (VA) medical centers using regional health information exchange (HIE) networks from March 2016 to December 2019. Alerts targeted VA-based primary care teams when older patients (aged 65+ years) were hospitalized or attended emergency departments (ED) outside the VA system. We employed a concurrent cohort study to compare postdischarge outcomes between patients whose providers received ENS alerts and those that did not (usual care). Outcome measures included: timely follow-up postdischarge (actual phone call within 7 days or an in-person primary care visit within 30 days) and all-cause inpatient or ED readmission within 30 days. Generalized linear mixed models, accounting for clustering by primary care team, were used to compare outcomes between groups.ResultsCompared to usual care, veterans whose primary care team received notification of non-VA acute care encounters were 4 times more likely to have phone contact within 7 days (AOR = 4.10, P < .001) and 2 times more likely to have an in-person visit within 30 days (AOR = 1.98, P = .007). There were no significant differences between groups in hospital or ED utilization within 30 days of index discharge (P = .057).DiscussionENS was associated with increased timely follow-up following non-VA acute care events, but there was no associated change in 30-day readmission rates. Optimization of ENS processes may be required to scale use and impact across health systems.ConclusionGiven the importance of ENS to the VA and other health systems, this study provides guidance for future research on ENS for improving care coordination and population outcomes.Trial RegistrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02689076","term_id":"NCT02689076"}}NCT02689076. “Regional Data Exchange to Improve Care for Veterans After Non-VA Hospitalization.” Registered February 23, 2016.     

Evaluating the impact of an integrated computer-based decision support with person-centered analytics for the management of asthma in primary care: a randomized controlled trial

Background Computer-based decision support has been effective in providing alerts for preventive care. Our objective was to determine whether a personalized asthma management computer-based decision support increases the quality of asthma management and reduces the rate of out-of-control episodes.Methods A cluster-randomized trial was conducted in Quebec, Canada among 81 primary care physicians and 4447 of their asthmatic patients. Patients were followed from the first visit for 3–33 months. The physician control group used the Medical Office of the 21st century (MOXXI) system, an integrated electronic health record. A custom-developed asthma decision support system was integrated within MOXXI and was activated for physicians in the intervention group.Results At the first visit, 9.8% (intervention) to 12.9% (control) of patients had out-of-control asthma, which was defined as a patient having had an emergency room visit or hospitalization for respiratory-related problems and/or more than 250 doses of fast-acting β-agonist (FABA) dispensed in the past 3 months. By the end of the trial, there was a significant increase in the ratio of doses of inhaled corticosteroid use to fast-acting β-agonist (0.93 vs. 0.69: difference: 0.27; 95% CI: 0.02–0.51; P = 0.03) in the intervention group. The overall out-of-control asthma rate was 54.7 (control) and 46.2 (intervention) per 100 patients per year (100 PY), a non-significant rate difference of −8.7 (95% CI: −24.7, 7.3; P = 0.29). The intervention’s effect was greater for patients with out-of-control asthma at the beginning of the study, a group who accounted for 44.7% of the 5597 out-of-control asthma events during follow-up, as there was a reduction in the event rate of −28.4 per 100 PY (95% CI: −55.6, −1.2; P = 0.04) compared to patients with in-control asthma at the beginning of the study (−0.08 [95% CI: −10.3, 8.6; P = 0.86]).Discussion This study evaluated the effectiveness of a novel computer-assisted ADS system that facilitates systematic monitoring of asthma control status, follow-up of patients with out of control asthma, and evidence-based, patient-specific treatment recommendations. We found that physicians were more likely to use ADS for out-of-control patients, that in the majority of these patients, they were advised to add an inhaled corticosteroid or a leukotriene inhibitor to the patient s treatment regimen, and the intervention significantly increased the mean ratio of inhaled corticosteroids to FABA during follow-up. It also reduced the rate of out-of-control episodes during follow up among patients whose asthma was out-of-control at the time of study entry. Future research should assess whether coupling patient-specific treatment recommendations, automated follow-up, and home care with comparative feedback on quality and outcomes of care can improve guideline adoption and care outcomes.Conclusions A primary care-personalized asthma management system reduced the rate of out-of-control asthma episodes among patients whose asthma was poorly controlled at the study’s onset.Trial Registration Clinicaltrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00170248","term_id":"NCT00170248"}}NCT00170248 http://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT00170248","term_id":"NCT00170248"}}NCT00170248?term=Asthma&spons=McGill+University&state1=NA%3ACA%3AQC&rank=2     

An Open-label,Self-control,Prospective Study on Cognitive Function,Academic Performance,and Tolerability of Osmotic-release Oral System Methylphenidate in Children with Attention-deficit Hyperactivity Disorder

Background:

Attention-deficit hyperactivity disorder (ADHD) is the most common mental and behavioral disorder in school-aged children. This study evaluated the effect of osmotic-release oral system (OROS) methylphenidate (MPH) on cognitive function and academic performance of Chinese school-aged children with ADHD.

Methods:

This 12-week, prospective, multicenter, open-label, self-controlled study enrolled 153 Chinese school-aged children with ADHD and 41 non-ADHD children. Children with ADHD were treated with once-daily OROS-MPH (18 mg, 36 mg, or 54 mg). The primary endpoints were Inattention/Overactivity (I/O) with Aggression Conners Behavior Rating Scale (IOWA) and Digit Span Test at week 12 compared with baseline. Secondary endpoints included opposition/defiant (O/D) subscale of IOWA, Clinical Global Impression (CGI), Coding Test, Stroop Color-word Test, Wisconsin Card Sorting Test (WCST), academic performance on teacher-rated school examinations, and safety at week 12 compared with baseline. Both non-ADHD and ADHD children received the same frequency of cognitive operational test to avoid the possible bias caused by training.

Results:

A total of 128 patients were evaluated with cognitive assessments. The OROS-MPH treatment significantly improved IOWA Conners I/O subscale scores at week 12 (3.8 ± 2.3) versus baseline (10.0 ± 2.4; P < 0.0001). Digit Span Test scores improved significantly (P < 0.0001) with a high remission rate (81.1%) at week 12 versus baseline. A significant (P < 0.0001) improvement was observed in O/D subscale of IOWA, CGI, Coding Test, Stroop Color-word Test, WCST, and academic performance at week 12 versus baseline. Very few practice-related improvements were noticed in the non-ADHD group at week 12 compared with baseline. No serious adverse events and deaths were reported during the study.

Conclusions:

The OROS-MPH treatment effectively controlled symptoms of ADHD and significantly improved academic performance and cognitive function of Chinese school-aged children with ADHD. The treatment was found to be safe and generally well-tolerated over 12 weeks.

Trial Registration:

ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT01933880","term_id":"NCT01933880"}}NCT01933880; http://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT01933880","term_id":"NCT01933880"}}NCT01933880?term=CONCERTAATT4099&rank=1