METHODS: This multicenter randomized double-blind placebo-controlled phase 2 trial included 110 solid malignant tumor patients (stage II-IV) undergoing chemotherapy. They were randomly selected and provided oral Nuvastatic™ 1000 mg (N = 56) or placebo (N = 54) thrice daily for 9 weeks. The primary outcomes were fatigue (Brief Fatigue Inventory (BFI)) and Visual Analog Scale for Fatigue (VAS-F)) scores measured before and after intervention at baseline and weeks 3, 6, and 9. The secondary outcomes were mean group difference in the vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36) and urinary F2-isoprostane concentration (an oxidative stress biomarker), Eastern Cooperative Oncology Group scores, adverse events, and biochemical and hematologic parameters. Analysis was performed by intention-to-treat (ITT). Primary and secondary outcomes were assessed by two-way repeated-measures analysis of variance (mixed ANOVA).
RESULTS: The Nuvastatic™ group exhibited an overall decreased fatigue score compared with the placebo group. Compared with the placebo group, the Nuvastatic™ group significantly reduced BFI-fatigue (BFI fatigue score, F (1.4, 147) = 16.554, p
OBJECTIVES: This study sought to evaluate the safety and efficacy of ninerafaxstat in nHCM.
METHODS: Patients with hypertrophic cardiomyopathy and left ventricular outflow tract gradient <30 mm Hg, ejection fraction ≥50%, and peak oxygen consumption <80% predicted were randomized to ninerafaxstat 200 mg twice daily or placebo (1:1) for 12 weeks. The primary endpoint was safety and tolerability, with efficacy outcomes also assessed as secondary endpoints.
RESULTS: A total of 67 patients with nHCM were enrolled at 12 centers (57 ± 11.8 years of age; 55% women). Serious adverse events occurred in 11.8% (n = 4 of 34) in the ninerafaxstat group and 6.1% (n = 2 of 33) of patients in the placebo group. From baseline to 12 weeks, ninerafaxstat was associated with significantly better VE/Vco2 (ventilatory efficiency) slope compared with placebo with a least-squares (LS) mean difference between the groups of -2.1 (95% CI: -3.6 to -0.6; P = 0.006), with no significant difference in peak VO2 (P = 0.90). The Kansas City Cardiomyopathy Questionnaire Clinical Summary Score was directionally, though not significantly, improved with ninerafaxstat vs placebo (LS mean 3.2; 95% CI: -2.9 to 9.2; P = 0.30); however, it was statistically significant when analyzed post hoc in the 35 patients with baseline Kansas City Cardiomyopathy Questionnaire Clinical Summary Score ≤80 (LS mean 9.4; 95% CI: 0.3-18.5; P = 0.04).
CONCLUSIONS: In symptomatic nHCM, novel drug therapy targeting myocardial energetics was safe and well tolerated and associated with better exercise performance and health status among those most symptomatically limited. The findings support assessing ninerafaxstat in a phase 3 study.
OBJECTIVE: We have conducted a systematic review of two major (FIGHT and LIVE) placebo-controlled trials of liraglutide and its clinical effect on the ejection fraction of subjects with heart failure.
METHODS: Medline data was retrieved for trials involving liraglutide from 2012 to 2020. The inclusion criteria for trials were: subjects with or without type 2 diabetes mellitus (T2DM), subjects with heart failure with rLVEF, major trials (phase II or III) on liraglutide, trials included liraglutide with defined efficacy primary outcome of patients with heart failure with rLVEF. The search was limited to the English language, whereby two trials [FIGHT and LIVE] had been included and two trials were excluded due to different primary outcomes. Participants (541) had been randomized for either liraglutide or placebo for 24 weeks.
RESULTS: In the FIGHT trial the primary intention-to-treat, sensitivity, and diabetes subgroup analyses have shown no significant between-group difference in the global rank scores (mean rank of 146 in the liraglutide group versus 156 in the placebo group; Wilcoxon rank-sum P=.31), number of deaths, re-hospitalizations for heart failure, or the composite of death or change in NT-pro BNP level (P= .94). In the LIVE trial, the change in the left ventricular ejection fraction (LVEF) from baseline to week 24 was not significantly different between treatment groups. The overall discontinuation rate of liraglutide was high in the FIGHT trial (29%, 86) as compared to that in the LIVE trial (11.6%, 28).
CONCLUSION: FIGHT and LIVE trials have demonstrated that liraglutide use in subjects with heart failure and rLVEF was implicated with an increased adverse risk of heart failure-related outcomes.
METHODS: A three-limbed double-blinded randomized control trial was conducted in a Level 3 neonatal intensive care unit. Forty five preterm neonates undergoing ROP screening were included. Eligible babies were randomly assigned to one of the three groups that orally received either expressed breast milk (n = 14), 10% dextrose solution (n = 14) or sterile water (n = 17), one minute before eye examination. The outcome measure was PIPP score.
RESULTS: All 3 groups were similar in baseline characteristics. The mean PIPP scores were comparable (p = 0.18) in the three groups (11.8 ± 2.8 vs. 9.8 ± 3.3 vs. 10.2 ± 2.9). The behavioral and physiological variables were also similar across all three groups.
CONCLUSIONS: Expressed breast milk, 10% dextrose or sterile water administered orally before ROP screening in preterm neonates have similar analgesic effects and do not significantly alleviate pain during the procedure.
DESIGN: A double-blind, cluster-randomized approach was used as a randomization method for this study to evaluate the stress management interventional program.
METHODS: A cluster-randomized controlled trial was carried out in eight comprehensive healthcare centres in Amman city, Jordan; four centres were randomly assigned to each experimental and control group. One hundred and seventy nurses were selected randomly from March 2019 - August 2019 and data were collected by using the Nursing Stress Scale & brief COPE over three data collection times. Both descriptive and inferential statistics (repeated measure ANOVA, Independent t test, and chi-squared) were used to answer the research questions of this study.
RESULTS: The results showed that both the levels of occupational stress and coping strategies were significantly different between the two study groups over the three data collection points (p method that can be used to reduce stress levels and improve coping strategies for public health nurses. The implementation of stress management interventions in health care is likely to help nurses manage occupational stress in practice.
IMPACT: Nurses suffer from a high level of occupational stress. In particular, approximately74% of nurses experience severe occupational stress, which can lead to many mental and physical disorders. However, nurses were less able to utilize the correct stress preventive strategies due to gaps in knowledge, skills, and awareness. This study contributed to the provision of empirical evidence of the effectiveness of the stress management program in reducing occupational stress and improving coping strategies among public health nurses. A stress management intervention program is a valuable non-invasive method that can be used by healthcare organizations to reduce stress levels and improve coping strategies for nurses in practice.
CLINICAL TRIAL REGISTRATION NUMBER: NCT03833986.
OBJECTIVES: To compare the efficacy of 1.8 and 3.6 mL of the same anaesthetic solution for IANBs when treating mandibular teeth with irreversible pulpitis.
METHODS: A literature search was performed in PubMed, Scopus and EBSCOhost databases until May 2020. Randomized clinical trials published in English, comparing 1.8 with 3.6 mL of the same anaesthetic solution for IANBs in permanent mandibular teeth with irreversible pulpitis, were included. The risk of bias of the included trials was appraised using the revised Cochrane risk of bias tool. A meta-analysis was performed using the random-effects model. The effect of random errors on the results of the meta-analysis was evaluated by trial sequential analysis and the quality of evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.
RESULTS: Four clinical trials involving 280 teeth from patients with ages ranging from 18 to 65 years were included. Among the four trials, three were categorized as having a 'low' risk of bias and one was categorized as having 'some concerns'. The primary meta-analysis revealed that 3.6 mL of anaesthetic solution when administered for IANBs was associated with significantly greater success rates compared with 1.8 mL (RR = 1.94; 95% CI, 1.07, 3.52; I2 = 77%). Similarly, the results of the sensitivity analysis (restricting trials only to those that used the Heft-Parker visual analogue pain scale) revealed that the use of 3.6 mL significantly increased the success of IANBs compared with 1.8 mL. The trial sequential analysis confirmed the evidence for the beneficial effect of 3.6 mL to achieve success for IANBs was 'conclusive'. The quality of evidence was graded as 'high'.
CONCLUSION: Increasing the volume of anaesthetic solution from 1.8 to 3.6 mL improved the success rate for IANBs in mandibular molars with irreversible pulpitis. The quality of the evidence was 'high'. Future high-quality clinical trials are required with different types of anaesthetic solutions and other types of teeth.
METHODS: Patients undergoing elective midline laparotomy through standardized incisions in two tertiary hospitals from February 2017 to September 2018 were randomized to either LS or SS. The primary outcome was post-operative patient-controlled analgesia morphine usage at 24 h. Secondary outcomes were presence of surgical site infection and length of hospital stay (LOHS). Categorical variables were analysed using chi-squared analysis. Outcomes of study were tested for normal distribution. Skewed data were analysed using Mann-Whitney U-test.
RESULTS: Eighty-six patients were recruited (42 SS and 44 LS). The median age was 66 (interquartile range (IQR) 15). Majority were males (62.8%) and Chinese (50%). The median incision length was 17 cm in both groups. The median patient-controlled analgesia morphine usage 24 h post-operatively did not differ significantly (SS 21 mg, IQR 28.3; LS 18.5 mg, IQR 33.8, P = 0.829). The median pain score at rest (SS 1, IQR 1; LS 1, IQR 2, P = 0.426) and movement (SS 3, IQR 1; LS 3, IQR 2, P = 0.307) did not differ significantly. LOHS was shorter in the SS group (SS 6, IQR 4; LS 8, IQR 5, P = 0.034). The rate of surgical site infection trended lower in the SS group with no statistical difference.
CONCLUSION: There were no differences in post-operative pain between SS and LS but we found that there were shorter LOHS in SS arm as secondary outcome.
METHODS AND ANALYSIS: At least 51 patients with an acute GPP flare will be randomised 2:1 to receive a single 900 mg intravenous dose of spesolimab or placebo and followed for up to 28 weeks. The primary endpoint is a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (pustule clearance) at Week 1. The key secondary endpoint is a GPPGA score of 0 or 1 (clear or almost clear) at Week 1. Safety will be assessed over the study duration by the occurrence of treatment-emergent adverse events. Blood and skin biopsies will be collected to assess biomarkers. Superiority of spesolimab over placebo in the proportion of patients achieving the primary and key secondary endpoints will be evaluated.
ETHICS AND DISSEMINATION: The study complies with the ethical principles of the Declaration of Helsinki, the International Council for Harmonisation's Good Clinical Practice and local regulations. Ethics committee approvals have been obtained for each centre from all participating countries and are listed in online supplementary file 1. Primary results will be published in a peer-reviewed journal.
TRIAL REGISTRATION DETAILS: ClinicalTrials.gov identifier: NCT03782792; Pre-results.
METHODS AND ANALYSIS: This study is a single-centre double-blind randomised placebo-controlled trial. Sixty-eight patients will be randomised to receive under ultrasound guidance either a single injection of leucocyte-rich PRP (LR-PRP) or normal saline. All patients will undergo a standardised hamstring rehabilitation programme under the supervision of a sports physiotherapist. Outcome data will be collected before intervention (baseline), and thereafter on a weekly basis. The primary outcome measure is the duration to return-to-play. It is defined as the duration (in days) from the date on which the injury occurred until the patients were pain-free, able to perform the active knee extension test and have regained hamstring muscle strength. Secondary outcome measures include assessment of pain intensity and the effect of pain on to day-to-day functions using the self-reported Brief Pain Inventory-Short Form questionnaire. Both the primary and secondary outcomes were assessed at baseline and thereafter once a week until return to play. Also, hamstring injury recurrence within the first 6 months after recovery will be monitored via telephone. The results of this study will provide insights into the effect of LR-PRP in muscle and may help to identify the best PRP application protocol for muscle injuries.
ETHICS AND DISSEMINATION: Ethics approval were obtained from the Medical Research Ethics Committee of the University of Malaya Medical Centre. Results of this trial will be submitted for publication in a peer-reviewed journal.
TRIAL REGISTRATION NUMBER: ISRCTN76844299.