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.     

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     

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.     

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     

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.     

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.     

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     

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 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.     

三维容积超声测量部分肢体体积在胎儿体重估测中的应用价值

目的分析三维容积超声测量部分肢体体积在胎儿体重估测中的应用价值情况。方法选择2015年4月至2019年4月在安阳市第三人民医院接受检查以及分娩的产妇206例的临床资料。产妇均接受三维超声部分肢体体积联合二维超声检查,分析其结果。结果把出生体重和超声参数开展相关性分析,探究大腿中段50%体积(TVol)、上臂中段50%体积(AVol)、大腿中段软组织厚度情况(STT)、腹围(AC)、股骨长(FL)、头围(HC)、双顶径(BPD)与新生儿出生体重呈现为线性关系。相关系数(r)分别为:0.816、0.701、0.544、0.590、0.377、0.411、0.399(P<0.05)。将新生儿出生体重视为因变量,把TVol、AVol、STT、AC、FL、HC、BPD视为自变量,开展多元回归分析依照具体的回归结果,TVol、AVol、AC、HC视为自变量,拟出多元线性回归方程,即:y=-2.751.157+6.785x1+8.775x2+13.594x3+4.582x4。对R方加以调整为0.795,证明拟合方程能体现出原始性数据。回归方程结果:F=51.258,P=0.000。结论利用三维超声可测量胎儿部分肢体体积,可在超声预测胎儿体重中发挥非常重要的作用,且该法有着操作简单、重复性高的优点,因此值得进一步在临床中推广应用。     

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     

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).     

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     

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     

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.     

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).     

A double-blind,randomized, placebo- and positive-controlled phase III trial of 1% benvitimod cream in mild-to-moderate plaque psoriasis

BackgroundBenvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis.MethodsWe randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician''s global assessment (sPGA) at week 12.ResultsThe results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported.ConclusionDuring this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis.Trial RegistrationChinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.     

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.