A multicentre phase III study comparing efficacy and safety of novel extended-release versus conventional formulation of dydrogesterone in Indian patients with endometriosis

Background: The aim of the study was to compare the efficacy and safety of novel once-daily extended-release (ER) dydrogesterone 20 mg versus conventional twice-daily dydrogesterone 10 mg in Indian patients with endometriosis. Methods: A phase III prospective, randomized, double-blind, single-dummy, two-arm, active-controlled, parallel, multicenter study was performed in six gynecology centers across India. The patients of 18 to 45 years of age with a confirmed diagnosis of endometriosis on ultrasonography (USG) and having endometriosis-associated pelvic pain score (EAPP) of at least 30 mm on a 100 mm visual analog scale (VAS) were randomly assigned to a 1:1 ratio to either once-daily dydrogesterone ER 20 mg or twice-daily dydrogesterone 10 mg arms for a treatment period of 90 days. The primary outcome was a change from baseline in EAPP score at the end of the treatment. Results: A total of 228 patients with a mean age of 31.8±6.9 years were enrolled in the study. At day 90, both the treatment arms showed a significant reduction (p<0.05) in EAPP score from baseline (i.e. -34.2±15.3 mm and -33.1±14.8 mm in once daily dydrogesterone ER and twice daily dydrogesterone 10 mg, respectively), with no significant difference between the two arms (p=0.53). With both formulations, patients experienced a significant reduction in the size of endometrioma, serum vascular endothelial growth factors (VEGF) levels, use of rescue analgesics, and significant improvement in the health-related quality-of-life parameters. A favorable safety profile of dydrogesterone was confirmed, and no significant safety concerns were reported during the study. Conclusions: Once daily dydrogesterone ER 20 mg and twice daily dydrogesterone 10 mg demonstrated a significant and similar reduction in EAPP and all other secondary parameters along with marked improvements in parameters related to quality of life

Intermittent left cervical vagal nerve stimulation damages the stellate ganglia and reduces the ventricular rate during sustained atrial fibrillation in ambulatory dogs

BACKGROUND: The effects of intermittent open-loop vagal nerve stimulation (VNS) on the ventricular rate (VR) during atrial fibrillation (AF) remain unclear. OBJECTIVE: The purpose of this study was to test the hypothesis that VNS damages the stellate ganglion (SG) and improves VR control during persistent AF. METHODS: We performed left cervical VNS in ambulatory dogs while recording the left SG nerve activity (SGNA) and vagal nerve activity. Tyrosine hydroxylase (TH) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to assess neuronal cell death in the SG. RESULTS: We induced persistent AF by atrial pacing in 6 dogs, followed by intermittent VNS with short ON-time (14 seconds) and long OFF-time (66 seconds). The integrated SGNA and VR during AF were 4.84 mV·s (95% confidence interval [CI] 3.08-6.60 mV·s) and 142 beats/min (95% CI 116-168 beats/min), respectively. During AF, VNS reduced the integrated SGNA and VR, respectively, to 3.74 mV·s (95% CI 2.27-5.20 mV·s; P = .021) and 115 beats/min (95% CI 96-134 beats/min; P = .016) during 66-second OFF-time and to 4.07 mV·s (95% CI 2.42-5.72 mV·s; P = .037) and 114 beats/min (95% CI 83-146 beats/min; P = .039) during 3-minute OFF-time. VNS increased the frequencies of prolonged (>3 seconds) pauses during AF. TH staining showed large confluent areas of damage in the left SG, characterized by pyknotic nuclei, reduced TH staining, increased percentage of TH-negative ganglion cells, and positive TUNEL staining. Occasional TUNEL-positive ganglion cells were also observed in the right SG. CONCLUSION: VNS damaged the SG, leading to reduced SGNA and better rate control during persistent AF

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Organizational Factors Affecting Safety Implementation in Food Companies in Thailand

Thai food industry employs a massive number of skilled and unskilled workers. This may result in an industry with high incidences and accident rates. To improve safety and reduce the accident figures, this paper investigates factors influencing safety implementation in small, medium, and large food companies in Thailand. Five factors, i.e., management commitment, stakeholders’ role, safety information and communication, supportive environment, and risk, are found important in helping to improve safety implementation. The statistical analyses also reveal that small, medium, and large food companies hold similar opinions on the risk factor, but bear different perceptions on the other 4 factors. It is also found that to improve safety implementation, the perceptions of safety goals, communication, feedback, safety resources, and supervision should be aligned in small, medium, and large companies

A Safety Assessment Approach Using Safety Enablers and Results

Industrial safety is an important issue in Thailand, and attempts have been made to improve safety performance and accident records. This paper examines key criteria influencing safety improvement. Exploratory factor analysis confirms 9 safety criteria, including 5 “enablers” and 4 “results”, with a total of 47 associated attributes. A safety assessment approach is developed, using those 9 key criteria, to measure an organization’s current safety maturity level. Organizations can use the assessment approach to plan its safety improvement, and progress through to higher maturity levels by focusing on the weakest criteria shown in the assessment results with the lowest scores

A Safety Assessment Approach Using Safety Enablers and Results

Industrial safety is an important issue in Thailand, and attempts have been made to improve safety performance and accident records. This paper examines key criteria influencing safety improvement. Exploratory factor analysis confirms 9 safety criteria, including 5 “enablers” and 4 “results”, with a total of 47 associated attributes. A safety assessment approach is developed, using those 9 key criteria, to measure an organization’s current safety maturity level. Organizations can use the assessment approach to plan its safety improvement, and progress through to higher maturity levels by focusing on the weakest criteria shown in the assessment results with the lowest scores

Synthetic first-principles studies from phase equilibria to microstructural formation in the Fe-Pt L10 phase

Electronic-structure calculations, the cluster-variation method of statistical mechanics, and the phase-field method were combined in attempted first-principles calculations of phase equilibria and microstructural evo-lution associated with the disorder-L10 transition of the Fe-Pt system. The calculated disorder-L10 transition temperature was within similar to 10 K difference from the experimental value, and the locus of spinodal ordering temperature is placed in the phase diagram. The calculated microstructure demonstrates preferential growth of the ordered domain along the direction and, in the later period, an anisotropic morphology of an antiphase domain structure develops. We offered an interpretation from the atomistic point of view for this morphology. We therefore achieved consistent first-principles multiscale calculations of phase equilibria and microstructural evolution, bridging microscopic to mesoscopic scales without any adjusting parameters