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Rugby Fans in Training New Zealand (RUFIT NZ): a randomized controlled trial to assess the effectiveness of a healthy lifestyle program for overweight men delivered through professional rugby clubs.
Maddison, R, Hargreaves, EA, Jiang, Y, Calder, AJ, Wyke, S, Gray, CM, Hunt, K, Lubans, DR, Eyles, H, Draper, N, et al
The international journal of behavioral nutrition and physical activity. 2023;(1):37
Abstract
BACKGROUND A healthy lifestyle program that appeals to, and supports, overweight and obese New Zealand (NZ) European, Māori (indigenous) and Pasifika men to achieve weight loss is urgently needed. A pilot program inspired by the successful Football Fans in Training program but delivered via professional rugby clubs in NZ (n = 96) was shown to be effective in weight loss, adherence to healthy lifestyle behaviors, and cardiorespiratory fitness in overweight and obese men. A full effectiveness trial is now needed. AIMS To determine the effectiveness and cost effectiveness of Rugby Fans In Training-NZ (RUFIT-NZ) on weight loss, fitness, blood pressure, lifestyle change, and health related quality of life (HRQoL) at 12- and 52-weeks. METHODS We conducted a pragmatic, two-arm, multi-center, randomized controlled trial in NZ with 378 (target 308) overweight and obese men aged 30-65 years, randomized to an intervention group or wait-list control group. The 12-week RUFIT-NZ program was a gender-sensitised, healthy lifestyle intervention delivered through professional rugby clubs. Each intervention session included: i) a 1-h workshop-based education component focused on nutrition, physical activity, sleep, sedentary behavior, and learning evidence-based behavior change strategies for sustaining a healthier lifestyle; and 2) a 1-h group-based, but individually tailored, exercise training session. The control group were offered RUFIT-NZ after 52-weeks. The primary outcome was change in body weight from baseline to 52-weeks. Secondary outcomes included change in body weight at 12-weeks, waist circumference, blood pressure, fitness (cardiorespiratory and musculoskeletal), lifestyle behaviors (leisure-time physical activity, sleep, smoking status, and alcohol and dietary quality), and health-related quality of life at 12- and 52-weeks. RESULTS Our final analysis included 200 participants (intervention n = 103; control n = 97) who were able to complete the RUFIT-NZ intervention prior to COVID-19 restrictions. At 52-weeks, the adjusted mean group difference in weight change (primary outcome) was -2.77 kg (95% CI -4.92 to -0.61), which favored the intervention group. The intervention also resulted in favorable significant differences in weight change and fruit and vegetable consumption at 12-weeks; and waist circumference, fitness outcomes, physical activity levels, and health-related quality of life at both 12 and 52 weeks. No significant intervention effects were observed for blood pressure, or sleep. Incremental cost-effective ratios estimated were $259 per kg lost, or $40,269 per quality adjusted life year (QALY) gained. CONCLUSION RUFIT-NZ resulted in sustained positive changes in weight, waist circumference, physical fitness, self-reported physical activity, selected dietary outcomes, and health-related quality of life in overweight/obese men. As such, the program should be recommended for sustained delivery beyond this trial, involving other rugby clubs across NZ. TRIAL REGISTRATION Australia New Zealand Clinical Trials Registry, ACTRN12619000069156. Registered 18 January 2019, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376740 Universal Trial Number, U1111-1245-0645.
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Early Amino Acids in Extremely Preterm Infants and Neurodisability at 2 Years.
Bloomfield, FH, Jiang, Y, Harding, JE, Crowther, CA, Cormack, BE, ,
The New England journal of medicine. 2022;(18):1661-1672
Abstract
BACKGROUND Whether higher parenteral amino acid intake improves outcomes in infants with extremely low birth weight is unclear. METHODS In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned infants with birth weights of less than 1000 g at 8 neonatal intensive care units to receive amino acids at a dose of 1 g per day (intervention group) or placebo in addition to usual nutrition for the first 5 days after birth. The primary outcome was survival free from neurodisability as assessed with the Bayley Scales of Infant and Toddler Development and neurologic examination at 2 years, corrected for gestational age at birth. Secondary outcomes were the components of the primary outcome as well as the presence or absence of neonatal disorders, the rate of growth, and nutritional intake. RESULTS We enrolled 434 infants (217 per group) in this trial. Survival free from neurodisability was observed in 97 of 203 children (47.8%) in the intervention group and in 102 of 205 (49.8%) in the placebo group (adjusted relative risk, 0.95; 95% confidence interval [CI], 0.79 to 1.14; P = 0.56). Death before the age of 2 years occurred in 39 of 217 children (18.0%) in the intervention group and 42 of 217 (19.4%) in the placebo group (adjusted relative risk, 0.93; 95% CI, 0.63 to 1.36); neurodisability occurred in 67 of 164 children (40.9%) in the intervention group and 61 of 163 (37.4%) in the placebo group (adjusted relative risk, 1.16; 95% CI, 0.90 to 1.50). Neurodisability was moderate to severe in 27 children (16.5%) in the intervention group and 14 (8.6%) in the placebo group (adjusted relative risk, 1.95; 95% CI, 1.09 to 3.48). More children in the intervention group than in the placebo group had patent ductus arteriosus (adjusted relative risk, 1.65; 95% CI, 1.11 to 2.46). In a post hoc analysis, refeeding syndrome occurred in 42 of 172 children in the intervention group and 26 of 166 in the placebo group (adjusted relative risk, 1.64; 95% CI, 1.09 to 2.47). Eight serious adverse events occurred. CONCLUSIONS In infants with extremely low birth weight, extra parenteral amino acids at a dose of 1 g per day for 5 days after birth did not increase the number who survived free from neurodisability at 2 years. (Funded by the New Zealand Health Research Council and others; ProVIDe Australian New Zealand Clinical Trials Registry number, ACTRN12612001084875.).
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Effectiveness of Levoamlodipine Maleate for Hypertension Compared with Amlodipine Besylate: a Pragmatic Comparative Effectiveness Study.
Ma, W, Sun, N, Duan, C, Zhao, L, Hua, Q, Sun, Y, Dang, A, Gao, P, Qu, P, Cui, W, et al
Cardiovascular drugs and therapy. 2021;(1):41-50
Abstract
PURPOSE Antihypertensive treatment is the most important method to reduce the risk of cardiovascular events in hypertensive patients. However, there is scant evidence of the benefits of levoamlodipine maleate for antihypertensive treatment using a head-to-head comparison in the real-world. This study aims to examine the effectiveness of levoamlodipine maleate used to treat outpatients with primary hypertension compared with amlodipine besylate in a real-world setting. METHODS This was a pragmatic comparative effectiveness study carried out at 110 centers across China in outpatients with primary hypertension treated with levoamlodipine maleate or amlodipine besylate, with 24 months of follow-up. The primary outcomes used for evaluating the effectiveness were composite major cardiovascular and cerebrovascular events (MACCE), adverse reactions, and cost-effectiveness. RESULTS Among the included 10,031 patients, there were 482 MACCE, 223 (4.4%) in the levoamlodipine maleate group (n = 5018) and 259 (5.2%) in the amlodipine besylate group (n = 5013) (adjusted hazard ratio = 0.90, 95%CI: 0.75-1.08, P = 0.252). The levoamlodipine maleate group had lower overall incidences of any adverse reactions (6.0% vs. 8.4%, P < 0.001), lower extremity edema (1.1% vs. 3.0%, P < 0.001) and headache (0.7% vs. 1.1%, P = 0.045). There was a nearly 100% chance of the levoamlodipine maleate being cost-effective at a willingness to pay threshold of 150,000 Yuan per quality-adjusted life years (QALYs) gained, resulting in more QALYs (incremental QALYs: 0.00392) and cost savings (saving 2725 Yuan or 28.8% reduction in overall costs) per patient. CONCLUSION In conclusion, levoamlodipine maleate could reduce cost by 29% with a similar MACCE incidence rate and lower occurrence of adverse reactions (especially edema and headache) compared with amlodipine besylate. TRIAL REGISTRATION Clinicaltrials.gov NCT01844570 registered at May 1, 2013.
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Association of Maternal DNA Methylation and Offspring Birthweight.
Kheirkhah Rahimabad, P, Arshad, SH, Holloway, JW, Mukherjee, N, Hedman, A, Gruzieva, O, Andolf, E, Kere, J, Pershagen, G, Almqvist, C, et al
Reproductive sciences (Thousand Oaks, Calif.). 2021;(1):218-227
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Abstract
This study aims to evaluate the association of maternal DNA methylation (DNAm) during pregnancy and offspring birthweight. One hundred twenty-two newborn-mother dyads from the Isle of Wight (IOW) cohort were studied to identify differentially methylated cytosine-phosphate-guanine sites (CpGs) in maternal blood associated with offspring birthweight. Peripheral blood samples were drawn from mothers at 22-38 weeks of pregnancy for epigenome-wide DNAm assessment using the Illumina Infinium HumanMethylation450K array. Candidate CpGs were identified using a course of 100 repetitions of a training and testing process with robust regressions. CpGs were considered informative if they showed statistical significance in at least 80% of training and testing samples. Linear mixed models adjusting for covariates were applied to further assess the selected CpGs. The Swedish Born Into Life cohort was used to replicate our findings (n = 33). Eight candidate CpGs corresponding to the genes LMF1, KIF9, KLHL18, DAB1, VAX2, CD207, SCT, SCYL2, DEPDC4, NECAP1, and SFRS3 in mothers were identified as statistically significantly associated with their children's birthweight in the IOW cohort and confirmed by linear mixed models after adjusting for covariates. Of these, in the replication cohort, three CpGs (cg01816814, cg23153661, and cg17722033 with p values = 0.06, 0.175, and 0.166, respectively) associated with four genes (LMF1, VAX2, CD207, and NECAP1) were marginally significant. Biological pathway analyses of three of the genes revealed cellular processes such as endocytosis (possibly sustaining an adequate maternal-fetal interface) and metabolic processes such as regulation of lipoprotein lipase activity (involved in providing substrates for the developing fetus). Our results contribute to an epigenetic understanding of maternal involvement in offspring birthweight. Measuring DNAm levels of maternal CpGs may in the future serve as a diagnostic tool recognizing mothers at risk for pregnancies ending with altered birthweights.
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Prospective assessment of diagnostic efficacy and safety of SonazoidTM and SonoVue® ultrasound contrast agents in patients with focal liver lesions.
Lv, K, Zhai, H, Jiang, Y, Liang, P, Xu, HX, Du, L, Chou, YH, Xie, X, Luo, Y, Lee, YJ, et al
Abdominal radiology (New York). 2021;(10):4647-4659
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OBJECTIVES To assess the respective diagnostic value of Sonazoid™ and SonoVue® for characterizing FLLs as benign or malignant and the corresponding safety. METHODS This prospective Phase 3 study was conducted at 17 centres in China and Korea (May 2014 to April 2015); 424 patients (20 to 80 years) with at least 1 untreated focal liver lesion (FLL) (< 10 cm in diameter) underwent a contrast-enhanced ultrasound (CEUS) examination (218 received Sonazoid of 0.12 μL microbubbles/kg; 206 received SonoVue of 2.4 mL). Three independent blinded readers evaluated pre- and post-contrast images characterising the FLLs as benign or malignant. RESULTS Sonazoid-enhanced and SonoVue-enhanced ultrasound provided a statistically significant improvement in specificity for all 3 readers comparing to unenhanced ultrasound (for Sonazoid: p = 0.0093, < 0.0001, 0.0011; for SonoVue: p = 0.002, 0.03, 0.12, respectively). Difference in accuracy improvement between the 2 groups was within the pre-specified non-inferiority margin of 20% for all 3 readers (6.1%, 95% CI: - 5.0 to 17.2; - 7.5%, 95% CI: - 18.4 to 3.5; - 0.3%, 95% CI: - 11.3 to 10.7). The diagnostic confidence level for all 3 readers increased with post-contrast images relative to pre-contrast images. Both contrast agents were well tolerated. CONCLUSION Results showed a similar efficacy for Sonazoid™ and SonoVue® in diagnosing FLLs as benign or malignant, and underlined the benefit of CEUS imaging over unenhanced ultrasound imaging in reaching a confident diagnosis without having to refer patients for additional imaging exams.
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Pharmacokinetic and bioequivalence study of new S-1 capsule in Chinese cancer patients.
Chen, Y, Jiang, Y, Qu, J, Wang, Q, Bai, Y, Shi, J, Shi, Y, Chen, X, Yang, N, Heng, J, et al
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2020;:105384
Abstract
S-1 is a multicomponent capsule containing tegafur, gimeracil, and oteracil potassium that has shown anticancer activity against numerous tumor types. However, S-1 capsules from different manufacturing companies have shown variations in pharmacokinetics and safety. Therefore, this multicenter, single-dose, randomized-sequence, open-label, two-way, self-crossover study was conducted to evaluate the bioequivalence of a newly developed generic S-1 (New Times Pharmaceutical Co., Ltd., Shandong, China) and the original brand-name S-1 capsule (Taiho Pharmaceutical Co., Ltd., Japan). Furthermore, the safety profiles of both products were compared. A total of 70 patients with 18 types cancer including breast, lung, gastric, and colorectal recruited at 5 hospitals who were randomly and alternatively administered 50 mg of the reference and test S-1 with a 7-day interval. Plasma concentrations of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), oteracil potassium, and 5-fluorouracil were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters, including maximum drug concentration (Cmax), time to achieve Cmax (Tmax), half-life (t1/2, area under the concentration-time curve from 0-time t (AUC0-t), and AUC from 0-infinity (AUC0-∞) were determined using non-compartmental analysis with DAS2.0 software. Bioequivalence of the reference and test S-1 was evaluated according to 90% confidence intervals (CIs) for ratios of AUC and Cmax of S-1. Adverse events were evaluated by monitoring symptoms, physical and laboratory examinations, electrocardiogram, and subject interviews. No significant difference was observed in plasma concentrations and pharmacokinetic profiles of tegafur, CDHP, oteracil potassium, or 5-fluorouracil (p > 0.05) among cancer patients treated with the reference or test S-1 formulation. The 90% CIs of Cmax, AUC0-t, and AUC0-∞ ratios were within the 80%-125% limit. The generic S-1 caused eight mild adverse events including liver dysfunction, diarrhea, nausea, fatigue, abnormal blood electrolytes, hyperglycemia, and dermal toxicity. Similarly, 18 mild adverse events were observed including dysarteriotony, diarrhea, nausea, fatigue, fever, hematotoxicity, abnormal blood electrolytes, hyperglycemia, dermal toxicity, and joint pain. There were no differences in the adverse event incidence between the two formulations. In conclusion, the newly developed generic S-1 showed similar pharmacokinetics to those of an original brand-name S-1 in cancer patients, thereby indicating bioequivalence. Furthermore, both treatments were well tolerated, suggesting that the cost-effective generic S-1 should be considered as a feasible option when treating patients.
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Eldecalcitol increases bone mineral density in Chinese osteoporotic patients without vitamin D or calcium supplementation.
Jiang, Y, Tang, H, Ma, X, Cheng, Q, Lin, H, Jin, X, Zhang, Z, Yu, W, He, S, Kobayashi, T, et al
Journal of bone and mineral metabolism. 2019;(6):1036-1047
Abstract
Eldecalcitol increased bone mineral density (BMD) and prevented vertebral fractures in vitamin D-sufficient osteoporotic subjects. However, the effect of eldecalcitol on BMD under vitamin D insufficiency is unknown. We examined the effect of eldecalcitol on BMD compared with alfacalcidol in osteoporotic patients without vitamin D or calcium supplementation. This is a randomized, double-blind, active comparator trial. 265 Chinese osteoporotic patients were randomly assigned to receive 0.75 μg eldecalcitol or 1.0 μg alfacalcidol for 12 months without vitamin D or calcium supplementation. Baseline calcium intakes were less than 550 mg/day and mean serum 25-hydroxyvitamin D [25(OH)D] was below 43 nmol/L in both groups. Baseline BMD tended to be lower in patients with lower calcium intake and serum 25(OH)D. Lumbar BMD increased by 2.05% higher in eldecalcitol than alfacalcidol group at 12 months. Total hip and femoral neck BMD also increased by 1.33 and 1.78%, respectively, in the eldecalcitol than the alfacalcidol group. The effect of eldecalcitol on BMD was not affected by serum 25(OH)D or calcium intake. The incidence of adverse events was not different between the two groups. Incidence of hypercalcemia in the edecalcitol group was not affected by serum 25(OH)D. In conclusion, baseline BMD tended to be lower in patients with low calcium intake and serum 25(OH)D. Eldecalcitol increased lumbar and hip BMD more than alfacalcidol regardless of serum 25(OH)D or calcium intake without vitamin D or calcium supplementation. These results suggest that eldecalcitol is effective in increasing the BMD of osteoporotic patients regardless of vitamin D status or calcium intake.Clinical Trial Registration number JAPIC CTI 152904.
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Effects and costs of real-time cardiac telerehabilitation: randomised controlled non-inferiority trial.
Maddison, R, Rawstorn, JC, Stewart, RAH, Benatar, J, Whittaker, R, Rolleston, A, Jiang, Y, Gao, L, Moodie, M, Warren, I, et al
Heart (British Cardiac Society). 2019;(2):122-129
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OBJECTIVE Compare the effects and costs of remotely monitored exercise-based cardiac telerehabilitation (REMOTE-CR) with centre-based programmes (CBexCR) in adults with coronary heart disease (CHD). METHODS Participants were randomised to receive 12 weeks of telerehabilitation or centre-based rehabilitation. REMOTE-CR provided individualised exercise prescription, real-time exercise monitoring/coaching and theory-based behavioural strategies via a bespoke telerehabilitation platform; CBexCR provided individualised exercise prescription and coaching via established rehabilitation clinics. Outcomes assessed at baseline, 12 and/or 24 weeks included maximal oxygen uptake (V̇O2max, primary) modifiable cardiovascular risk factors, exercise adherence, motivation, health-related quality of life and programme delivery, hospital service utilisation and medication costs. The primary hypothesis was a non-inferior between-group difference in V̇O2max at 12 weeks (inferiority margin=-1.25 mL/kg/min); inferiority margins were not set for secondary outcomes. RESULTS 162 participants (mean 61±12.7 years, 86% men) were randomised. V̇O2 max was comparable in both groups at 12 weeks and REMOTE-CR was non-inferior to CBexCR (REMOTE-CR-CBexCR adjusted mean difference (AMD)=0.51 (95% CI -0.97 to 1.98) mL/kg/min, p=0.48). REMOTE-CR participants were less sedentary at 24 weeks (AMD=-61.5 (95% CI -117.8 to -5.3) min/day, p=0.03), while CBexCR participants had smaller waist (AMD=1.71 (95% CI 0.09 to 3.34) cm, p=0.04) and hip circumferences (AMD=1.16 (95% CI 0.06 to 2.27) cm, p=0.04) at 12 weeks. No other between-group differences were detected. Per capita programme delivery (NZD1130/GBP573 vs NZD3466/GBP1758) and medication costs (NZD331/GBP168 vs NZD605/GBP307, p=0.02) were lower for REMOTE-CR. Hospital service utilisation costs were not statistically significantly different (NZD3459/GBP1754 vs NZD5464/GBP2771, p=0.20). CONCLUSION REMOTE-CR is an effective, cost-efficient alternative delivery model that could-as a complement to existing services-improve overall utilisation rates by increasing reach and satisfying unique participant preferences.
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Calcium: magnesium intake ratio and colorectal carcinogenesis, results from the prostate, lung, colorectal, and ovarian cancer screening trial.
Zhao, J, Giri, A, Zhu, X, Shrubsole, MJ, Jiang, Y, Guo, X, Ness, R, Seidner, DL, Giovannucci, E, Edwards, TL, et al
British journal of cancer. 2019;(9):796-804
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BACKGROUND We aimed to evaluate the associations between calcium and various stages of colorectal carcinogenesis and whether these associations are modified by the calcium to magnesium (Ca:Mg) ratio. METHODS We tested our hypotheses in the prostate lung, colorectal and ovarian cancer screening trial. RESULTS Calcium intake did not show a dose-response association with incident adenoma of any size/stage (P-trend = 0.17), but followed an inverse trend when restricted to synchronous/advanced adenoma cases (P-trend = 0.05). This inverse trend was mainly in participants with Ca:Mg ratios between 1.7 and 2.5 (P-trend = 0.05). No significant associations were observed for metachronous adenoma. Calcium intake was inversely associated with CRC (P-trend = 0.03); the association was primarily present for distal CRC (P-trend = 0.01). The inverse association between calcium and distal CRC was further modified by the Ca:Mg ratio (P-interaction < 0.01); significant dose-response associations were found only in participants with a Ca:Mg ratio between 1.7 and 2.5 (P-trend = 0.04). No associations for calcium were found in the Ca:Mg ratio above 2.5 or below 1.7. CONCLUSION Higher calcium intake may be related to reduced risks of incident advanced and/or synchronous adenoma and incident distal CRC among subjects with Ca:Mg intake ratios between 1.7 and 2.5.
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Effect of a Multifaceted Quality Improvement Intervention on Hospital Personnel Adherence to Performance Measures in Patients With Acute Ischemic Stroke in China: A Randomized Clinical Trial.
Wang, Y, Li, Z, Zhao, X, Wang, C, Wang, X, Wang, D, Liang, L, Liu, L, Wang, C, Li, H, et al
JAMA. 2018;(3):245-254
Abstract
IMPORTANCE In China and other parts of the world, hospital personnel adherence to evidence-based stroke care is limited. OBJECTIVE To determine whether a multifaceted quality improvement intervention can improve hospital personnel adherence to evidence-based performance measures in patients with acute ischemic stroke (AIS) in China. DESIGN, SETTING, AND PARTICIPANTS A multicenter, cluster-randomized clinical trial among 40 public hospitals in China that enrolled 4800 patients hospitalized with AIS from August 10, 2014, through June 20, 2015, with 12-month follow-up through July 30, 2016. INTERVENTIONS Twenty hospitals received a multifaceted quality improvement intervention (intervention group; 2400 patients), including a clinical pathway, care protocols, quality coordinator oversight, and performance measure monitoring and feedback. Twenty hospitals participated in the stroke registry with usual care (control group; 2400 patients). MAIN OUTCOMES AND MEASURES The primary outcome was hospital personnel adherence to 9 AIS performance measures, with co-primary outcomes of a composite of percentage of performance measures adhered to, and as all-or-none. Secondary outcomes included in-hospital mortality and long-term outcomes (a new vascular event, disability [modified Rankin Scale score, 3-5], and all-cause mortality) at 3, 6, and 12 months. RESULTS Among 4800 patients with AIS enrolled from 40 hospitals and randomized (mean age, 65 years; women, 1757 [36.6%]), 3980 patients (82.9%) completed the 12-month follow-up of the trial. Patients in intervention group were more likely to receive performance measures than those in the control groups (composite measure, 88.2% vs 84.8%, respectively; absolute difference, 3.54% [95% CI, 0.68% to 6.40%], P = .02). The all-or-none measure did not significantly differ between the intervention and control groups (53.8% vs 47.8%, respectively; absolute difference, 6.69% [95% CI, -0.41% to 13.79%], P = .06). New clinical vascular events were significantly reduced in the intervention group compared with the control group at 3 months (3.9% vs 5.3%, respectively; difference, -2.03% [95% CI, -3.51% to -0.55%]; P = .007), 6 months (6.3% vs 7.8%, respectively; difference, -2.18% [95% CI, -4.0% to -0.35%]; P = .02) and 12 months (9.1% vs 11.8%, respectively; difference, -3.13% [95% CI, -5.28% to -0.97%]; P = .005). CONCLUSIONS AND RELEVANCE Among 40 hospitals in China, a multifaceted quality improvement intervention compared with usual care resulted in a statistically significant but small improvement in hospital personnel adherence to evidence-based performance measures in patients with acute ischemic stroke when assessed as a composite measure, but not as an all-or-none measure. Further research is needed to understand the generalizability of these findings. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02212912.