Safety Variables Research Articles

Learning curves of open and endoscopic fetal spina bifida closure: systematic review and meta-analysis.

The Management of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida aperta (SBA). Recently developed alternative techniques may reduce maternal risks without compromising the fetal neuroprotective effects. The aim of this systematic review was to assess the learning curve (LC) of different fetal SBA closure techniques. MEDLINE, Web of Science, EMBASE, Scopus and Cochrane databases and the gray literature were searched to identify relevant articles on fetal surgery for SBA, without language restriction, published between January 1980 and October 2018. Identified studies were reviewed systematically and those reporting all consecutive procedures and with postnatal follow-up ≥ 12 months were selected. Studies were included only if they reported outcome variables necessary to measure the LC, as defined by fetal safety and efficacy. Two authors independently retrieved data, assessed the quality of the studies and categorized observations into blocks of 30 patients. For meta-analysis, data were pooled using a random-effects model when heterogeneous. To measure the LC, we used two complementary methods. In the group-splitting method, competency was defined when the procedure provided results comparable to those in the MOMS trial for 12 outcome variables representing the immediate surgical outcome, short-term neonatal neuroprotection and long-term neuroprotection at ≥ 12 months of age. Then, when raw patient data were available, we performed cumulative sum analysis based on a composite binary outcome defining successful surgery. The composite outcome combined four clinically relevant variables for safety (absence of extreme preterm delivery < 30 weeks, absence of fetal death ≤ 7 days after surgery) and efficacy (reversal of hindbrain herniation and absence of any neonatal treatment of dehiscence or cerebrospinal fluid leakage at the closure site). Of 6024 search results, 17 (0.3%) studies were included, all of which had low, moderate or unclear risk of bias. Fetal SBA closure was performed using standard hysterotomy (11 studies), mini-hysterotomy (one study) or fetoscopy by either exteriorized-uterus single-layer closure (one study), percutaneous single-layer closure (three studies) or percutaneous two-layer closure (one study). Only outcomes for standard hysterotomy could be meta-analyzed. Overall, outcomes improved significantly with experience. Competency was reached after 35 consecutive cases for standard hysterotomy and was predicted to be achieved after ≥ 57 cases for mini-hysterotomy and ≥ 56 for percutaneous two-layer fetoscopy. For percutaneous and exteriorized-uterus single-layer fetoscopy, competency was not reached in the 81 and 28 cases available for analysis, respectively, and LC prediction analysis could not be performed. The number of cases operated is correlated with the outcome of fetal SBA closure, and the number of operated cases required to reach competency ranges from 35 for standard hysterotomy to ≥ 56-57 for minimally invasive modifications. Our observations provide important information for institutions looking to establish a new fetal center, develop a new fetal surgery technique or train their team, and inform referring clinicians, potential patients and third parties. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

P1866TO INVESTIGATE THE EFFICACY AND SAFETY OF MOLIDUSTAT IN NON-DIALYSIS PATIENTS WITH RENAL ANEMIA WHO ARE NOT TREATED WITH ERYTHROPOIESIS-STIMULATING AGENTS: MIYABI ND-C

Abstract Background and Aims Anemia is a common complication of chronic kidney disease (CKD). A hypoxia-inducible factor prolyl-hydroxylase (HF-PH) inhibitor is developing as a new treatment option of renal anemia. Molidustat, an oral HIF-PH inhibitor, stimulated endogenous production of erythropoietin and was well tolerated in phase IIb clinical trials. The phase III program entitled MolIdustat once dailY improves renal Anemia By Inducing EPO (MIYABI) was conducted in Japan. Method MIYABI Non-Dialysis-Correction (ND-C) of Hb study (up to 52 weeks, randomized, darbepoetin-controlled, open-label) was conducted to investigate the efficacy and safety of molidustat (MO) in non-dialysis patients with renal anemia who are not treated with erythropoiesis-stimulating agents. Study drug doses were titrated regularly with the aim of correcting and maintaining the patients’ Hb values between the target range (11.0-13.0 g/dL). The primary efficacy variables were the mean Hb values during the evaluation period (30-36 weeks) and its change from baseline to demonstrate the non-inferiority of MO to darbepoetin alfa (DA) using a non-inferiority margin of 1.0g/dL. Safety variables included adverse events (AE). Prespecified primary analysis results up to 36 weeks are presented here. Results 82 patients were treated with a starting dose of 25mg of MO and 79 patients were treated with a starting dose of 30μg/2weeks of DA. The mean of baseline Hb values were 9.84 g/dL and 10.00 g/dL in the MO and DA group, respectively. MO increased the mean Hb values (rate of rise from baseline in Hb values at the first dose change up to 8 weeks: mean: 0.086 g/dL/week (95%CI; 0.047, 0.126)) and achieved the lower limit of target range at 12 weeks. MO maintained Hb values after 12 weeks, and for the mean Hb values during the evaluation period, the mean was 11.28 g/dL (95%CI; 11.07, 11.50). As the primary efficacy variables (the changes from baseline of mean Hb values during the evaluation period), the means were 1.45 g/dL (95%CI; 1.21, 1.68) and 1.70 g/dL (95%CI; 1.47, 1.92) in the MO and DA group, respectively. The LS mean difference was -0.38 (95%CI; -0.67, -0.08), therefore the non-inferiority of MO to DA was established. The mean (SD) doses during the study period were 45.33 (28.88) mg/day of MO and 17.87 (12.49) μg/week of DA. The most common maximum dose of MO was 25 mg (26 patients, 31.7%) followed by 75 mg (16 patients, 19.5%) and 50mg (14 patients, 17.1%). AEs were experienced in 84.1% of patients in the MO group and in 91.1% of patients in the DA group up to 36 weeks. The most common AEs occurred ≥ 5% of patients in any group were nasopharyngitis (20.7% and 25.3%, respectively) and worsening of chronic kidney disease (13.4% and 6.3%, respectively). Conclusion Correction and Maintenance effect of MO on the Hb values was investigated and the non-inferiority of MO to DA was established in non-dialysis patients with untreated anemia. The MO showed no new safety concern but further longitudinal investigation will be needed.

P1868TO INVESTIGATE THE EFFICACY AND SAFETY OF MOLIDUSTAT IN NON-DIALYSIS PATIENTS WITH RENAL ANEMIA WHO ARE TREATED WITH ERYTHROPOIESIS-STIMULATING AGENTS: MIYABI ND-M

Abstract Background and Aims Treatment with subcutaneous erythropoiesis-stimulating agent (ESA) is the standard of care for renal anemia in non-dialysis patients. A hypoxia-inducible factor prolyl-hydroxylase (HF-PH) inhibitor is an oral medication and might be a new treatment option of renal anemia. Molidustat mimics the physiological response to hypoxia, thereby stimulating endogenous EPO production by the kidneys. The phase III program entitled MolIdustat once dailY improves renal Anemia By Inducing EPO (MIYABI) was conducted in Japan. Method MIYABI Non-Dialysis- Maintenance (ND-M) of Hb study (up to 52 weeks, randomized, darbepoetin-controlled, open-label) was conducted to investigate the efficacy and safety of molidustat (MO) in non-dialysis patients with renal anemia who are treated with ESAs. A starting dose was in accordance with previous ESA dose and study drug doses were titrated regularly with the aim of maintaining the patients’ Hb values between the target range (11.0-13.0 g/dL). The primary efficacy variables were the mean Hb values during the evaluation period (30-36 weeks) and its change from baseline to demonstrate the non-inferiority of MO to darbepoetin alfa (DA) using a non-inferiority margin of 1.0 g/dL. Safety variables included adverse events. Prespecified primary analysis results up to 36 weeks are presented here. Results 82 patients were treated with MO, starting doses were 25 mg for 27 patients and 50 mg in 55 patients. 82 patients were treated with DA, starting doses were in accordance with previous ESA dose and interval. The mean of baseline Hb values were 11.31 g/dL and 11.27 g/dL in the MO and DA group, respectively. For the mean Hb values during the evaluation period in MO, the mean was 11.67 g/dL (95%CI; 11.48, 11.85) and the mean Hb values of 66 patients (80.5%) were within the target range. As the primary efficacy variables (the changes from baseline of mean Hb values during the evaluation period), the means were 0.35 g/dL (95%CI; 0.12, 0.58) and 0.26 g/dL (95%CI; 0.04, 0.48) in the MO and DA group, respectively. The LS mean difference was 0.13 (95%CI; -0.15, 0.40), therefore the non-inferiority of MO to DA was established. The mean (SD) doses during the study period were 52.16 (32.58) mg/day of MO and 21.33 (12.33) μg/week of DA. AEs were experienced in 87.8% of patients in the MO group and 89.0% of patients in the DA group up to 36 weeks. The most common AEs occurred ≥ 5% of patients in any group were nasopharyngitis (29.3% and 30.5%, respectively) and worsening of chronic kidney disease (12.2% and 7.3%, respectively). Conclusion Maintenance effect of MO on the Hb values was investigated and the non-inferiority of MO to DA was established in non-dialysis patients with anemia treated with ESAs. The MO showed no new safety concern but further longitudinal investigation will be needed.

Active School Transport among Children from Canada, Colombia, Finland, South Africa, and the United States: A Tale of Two Journeys.

Walking and biking to school represent a source of regular daily physical activity (PA). The objectives of this paper are to determine the associations of distance to school, crime safety, and socioeconomic variables with active school transport (AST) among children from five culturally and socioeconomically different country sites and to describe the main policies related to AST in those country sites. The analytical sample included 2845 children aged 9–11 years from the International Study of Childhood Obesity, Lifestyle and the Environment. Multilevel generalized linear mixed models were used to estimate the associations between distance, safety and socioeconomic variables, and the odds of engaging in AST. Greater distance to school and vehicle ownership were associated with a lower likelihood of engaging in AST in sites in upper-middle- and high-income countries. Crime perception was negatively associated to AST only in sites in high-income countries. Our results suggest that distance to school is a consistent correlate of AST in different contexts. Our findings regarding crime perception support a need vs. choice framework, indicating that AST may be the only commuting choice for many children from the study sites in upper-middle-income countries, despite the high perception of crime.

Preclinical evaluation of CLX-155, a novel prodrug of 5-FU for the treatment of cancer.

e15614 Background: CLX-155 is a novel prodrug of 5-FU, developed by adding two acetyl groups (ester bond) and a caprylic acid moiety (amide bond) to 5'-DFCR ring structure. CLX-155 is designed to have a differentiated ADME profile, with improved safety and efficacy over capecitabine. Here, we present the preclinical data of CLX-155 in comparison with capecitabine. Methods: Solubility/stability of CLX-155 was studied in buffers, simulated gastrointestinal fluids and liver microsomes. In vitro metabolite profiling in hepatocytes was done following standard protocol. An oral (gavage) dose range finding (DRF) toxicity, comparative oral pharmacokinetic study and antitumor activity in HCT-116 human colon cancer cell xenograft model was conducted in mice. DRF study in mice evaluated the toxicity of CLX-155 when administered at once daily doses of 100 to 1000 mg/kg/day for 7-days. The oral pharmacokinetics CLX-155/metabolites (5'-DFCR, 5'-DFUR and 5-FU) was determined in mice at MTD dose of 500 mg/kg and for capecitabine at 1000 mg/kg. Antitumor activity of CLX-155 was evaluated in Foxn1 athymic mice at 125, 250 and 500 mg/kg/day and for capecitabine at 1000 mg/kg/day. Treatment was performed for three consecutive weeks (5 days on; 2 days off per week). Results: The results of in-vitro studies confirmed an acceptable profile for further development of CLX-155. Maximum tolerated dose of CLX-155 in mice was 500 mg/kg/day. The key toxicity findings were consistent with the mechanism of action and comparable with capecitabine. Oral PK study in mice showed a lower plasma Cmax for 5'-DFCR, 5'-DFUR and 5-FU. Plasma AUCs of the metabolites were close to or higher than that of capecitabine, indicating an extended absorption or altered metabolism in comparison with capecitabine. CLX-155 caused significant, tumor growth inhibition at all the dose levels tested. Complete tumor regression was seen in 2/10 animals at 500 mg/kg/day of CLX-155. CLX-155 was better tolerated in the mouse xenograft study, no mortality in CLX-155 versus 2/10 in capecitabine group. Conclusions: CLX-155 has an excellent safety and a differentiated ADME profile in relation to capecitabine. This translated into an improved in-vivo antitumor activity for CLX-155 in the HCT 116 xenograft model in relation to capecitabine. Overall data indicate that CLX-155 could offer significant improvements over the currently approved capecitabine in terms of dose size, frequency of administration, safety and interpatient variability in pharmacokinetics.

Efficacy and safety of a low-dose continuous combined hormone replacement therapy with 0.5 mg 17β-estradiol and 2.5 mg dydrogesterone in subgroups of postmenopausal women with vasomotor symptoms

ObjectivesVarious combinations of estrogens and progestogens are available for menopausal hormone therapy that differ in their efficacy and safety profile. We evaluated the efficacy and long-term safety of low-dose estradiol (0.5 mg) / dydrogesterone (2.5 mg) in subgroups of postmenopausal women with vasomotor symptoms. Analysis: Efficacy analysis was performed on data from 2 previously published studies for subgroups defined by age, duration of menopause, and body mass index at baseline. The primary efficacy variable was the number of moderate to severe hot flushes from baseline to week 13. Long-term safety was evaluated in relation to age and duration of menopause. Safety variables included adverse events to week 52 and change from baseline to endpoint in laboratory and vital sign values. Results: The treatment difference seen in the overall population in favour of low-dose estradiol/dydrogesterone was also observed in the subgroups of patients aged 45 to < 55 years (p < 0.01) and ≥55 years (p < 0.05), with menopause duration of >12 months to <60 months (p < 0.05) and ≥ 60 months (p < 0.005), and with a BMI at baseline of <25 kg/m2 (p < 0.05) and 25 to <30 kg/m2 (p < 0.01). Low-dose estradilol/dydrogesterone was well tolerated across the different subgroups. The incidence of breast-related adverse events was very low. No breast malignancy was reported. Only one adverse endometrial outcome of simple hyperplasia was observed. Conclusion: The results of our analyses confirmed the consistent treatment effect on vasomotor symptoms and the favourable safety profile of 0.5 mg 17β estradiol and 2.5 mg dydrogesterone in different patient subgroups.

An Assessment of Food Safety Knowledge and Practices in the Ghanaian Hospitality Industry

Food safety is critical for public health and economic development. The hospitality industry offers a variety of food services, led by food handlers with diverse background. The aim of this paper is to evaluate food safety knowledge and practices among food handlers in the Ghanaian hospitality sectors, with the purpose of informing public policy and improving food safety. A cross-sectional survey study was conducted between February and May 2019. Data were obtained from food handlers working in the Ghanaian hospitality industry (N = 306). The findings of the study indicate that most (52.9%) respondents who work in restaurants had knowledge about food safety principles. Lack of training and education was identified by 63.1% of the respondents as a major barrier to food safety. Interestingly, 75.8% of the respondents indicated that food safety practice is not the responsibility of the kitchen staff only. Diarrhea (35.95%), cholera (35.62%), and typhoid (27.42%) were identified as major diseases associated with improper handling of food. Only 65.69% of the respondents undergo annual medical screening at their workplaces. There is correlation between food safety practice and variables such as marital status, type of residence, age, and education level. Educational campaigns coupled with strict law enforcement should be put in place to ensure that food safety rules and guideline are effectively implemented in the hospitality food industry. Training programs should be organized for food vendors and other stakeholders in the food industry as well. Finally, there should be proactive supervision by local government officials to ensure that good sanitation and hygienic conditions are maintained within the food sectors.

PROGRAM KESELAMATAN DAN KESEHATAN KERJA, KOMPETENSI DAN KOMITMEN ORGANISASI TERHADAP KINERJA KARYAWAN DEPARTEMEN HUMAN RESOURCES OPERATIONAL PADA PT. GAJAH TUNGGAL TBK

This is study aims to determine the effect of occupational safety and health, work competence and organizational commitment partially or simultaneously on the employee performance of the Human Resource Operations department at PT Gajah Tunggal, TBk. This study uses a descriptive quantitative research approach that relates to the numbers in the description describing in detail. For the sampling method in this is study the sampling method is used, namely saturated samples. The study sample was 55 respondents from employees of the operational human resources department at PT Gajah Tunggal, Tbk. so that the engineering approach with sampling used is saturated sample is expected to have a very small error gradation by being a population as a sample of 55 respondents. In this research. Analysis of the data used by researchers is with the help of calculating the SPSS 24 application to calculate the effect partially or simultaneously. Based on the results of simple regression and multiple regression in the SPSS 24 application. The results of the research can be partially proven that the occupational safety and health variables (X1) have a positive and significant effect on performance (Y) of 0.230 or 23%. The variable work competence (X2) has a positive and significant effect on performance (Y) of 0.503 or 50.3%. Organizational commitment variable (X3) has a positive and significant effect on performance (Y) of 0.434 or 43.4%. Simultaneously the occupational safety and health variables (X1), work competence (X2) and organizational commitment (X3) have a positive and significant effect on performance (Y) of 45.8%.Keywords: Occupational Safety And Health, Work Competence, Organizational Commitment, And Employee Performance

Time Matters: Adjusted Analysis of the Influence of Direct Transfer to Angiography-Suite Protocol in Functional Outcome.

Background and Purpose- Direct transfer to angiography-suite (DTAS) protocol is a promising measure to improve onset to recanalization time in patients who undergo endovascular treatment. The magnitude of the improvement of good outcome rates in function of time depends of several factors. We aim to analyze the benefit of DTAS according to time from symptom onset. Methods- Retrospective case-control study of 174 consecutive DTAS cases matched with 175 patients initially transferred to computed tomography (directly transferred to computed tomography) from February 2016 to June 2019. To obtain comparable groups on admission, cases and controls were matched by occlusion location, age (±2 years), baseline National Institutes of Health Stroke Scale score (±2 points), and time from symptoms onset to hospital arrival (±30 minutes). We analyzed the rate of good functional outcome at 3 months (modified Rankin Scale score, 0-2) and safety variables stratified in less or more than 3 hours from onset to arrive. Results- There were no significant differences regarding age, sex, or baseline National Institutes of Health Stroke Scale score. Median door-to-groin time was shorter in the DTAS patients (16 [3-21] minutes versus 70 [41.5-98.5]; P<0.01). DTAS patients presented lower National Institutes of Health Stroke Scale score at 24 hours (9 [3.5-17] versus 14 [5-19]; P=0.01) and a lower rate of symptomatic hemorrhagic transformation (4.6% versus 10.9%, P<0.03). At 90 days, DTAS patients had a higher rate of good functional outcome (43% versus 29%; odds ratio, 1.81 [95% CI, 1.14-2.87]; P=0.01). Better outcome in DTAS was observed in patients admitted in the 0 to 3 hours form onset window (n=156, odds ratio 2.63 [95% CI, 1.31-5.28]; P<0.01), but not in patients admitted in the 3 to 6 hours window (n=193, odds ratio, 1.37 [95% CI, 0.72-2.60]; P=0.2). Conclusions- DTAS seems a feasible and safe strategy to improve functional outcome in patients who undergo endovascular treatment mainly within 3 hours from symptoms onset.

Effect of Work Safety and Work Healthy Towards Employee's Productivity in PT. Sisirau Aceh Tamiang

This study aims to determine the effect of work safety and work healthy on employee productivity in the production department at PT. Sisirau Aceh Tamiang. This research is a type of quantitative research with a sample of 45 people. The data analysis method used is multiple linear regression analysis. Hypothesis testing is done through t test, F test, and the coefficient of determination (R2). Regression equation results obtained Y = 2.255 + 0.314X1 + 0.811X2 means that the constant value of 2.255 is the value of employee productivity before being influenced by work safety and health. The work safety regression coefficient is 0.314 and is positive, meaning that if work safety is increased the employee's work productivity will increase by 0.314 with a tcount&gt; ttable (2.333&gt; 1.68195) and significant (0.025 &lt;0.05). The work health regression coefficient is 0.118 and is positive, meaning that if work health is improved the employee's work productivity will increase by 0.811 with a tcount&gt; ttable (8.063&gt; 1.68195) and significant (0.000 &lt;0.05). The coefficient of determination (R2) of 0.614 or 61.4%, which means the work safety and health variables influence the work productivity of employees by 61.4% and the remaining 39.6% is influenced by other variables not examined in this study.

Estimation of Rock Load of Multi-Arch Tunnel with Cracks Using Stress Variable Method

In multi-arch tunnels, the increased rock load on the concrete lining of the main tunnel and side walls due to the excavation of adjacent tunnels is critical and must be considered in the design stage. Therefore, this study estimates the rock load of a multi-arch tunnel using two-dimensional numerical analysis, considering rock mass classifications, overburden, and construction steps. The rock load is estimated using two criteria: the factor of safety and stress variable. The rock load is underestimated when the factor of safety is applied to rock mass class III. However, the stress variable method reveals a reasonable rock load as overburden increases. Particularly, the rock load is estimated to be equal to the overburden in shallow tunnels and approximately 0.7 times the tunnel width in deep tunnels. Additionally, the crack-induced rock load is computed using back analysis at the excavation completion stage of adjacent tunnels, yielding the relation between the rock load height and the deformation modulus of the rock mass. Therefore, an accurate estimation of the rock load of multi-arch tunnels emphasizes the importance of a more economical and realistic design and must be addressed in the process of performance-based tunnel design.

SAT-432 Pharmacokinetics (PK) and Exposure-Response Relationship of Teprotumumab, an Insulin-Like Growth Factor-1 Receptor (IGF-1R) Blocking Antibody, in Active Thyroid Eye Disease (TED)

Introduction: Teprotumumab treatment resulted in statistically and clinically meaningful improvements across multiple facets of active TED and was generally well-tolerated in Phase 2 and 3 trials.1,2 An initial intravenous infusion of 10 mg/kg followed by 20 mg/kg every 3 weeks was selected based on in vitro activity and clinical PK profile, to maintain pharmacologically active exposures and >90% saturation of IGF-1R over dosing intervals and to achieve efficacy at a well-tolerated dose for this vision-threatening disease. Methods: Population PK analysis were performed on data from a Phase 1 oncology study (n=60)3 and Phase 2 and 3 trials in active TED (N=83)2,3 and covariate effect on PK was assessed. Exposure-response relationship was evaluated in TED studies for key efficacy endpoints (proptosis response rate, % patients with a clinical activity score value of 0 or 1, and diplopia responder rate) and selected safety variables (hyperglycemia and muscle spasms). Results: Teprotumumab PK was linear in TED patients and consistent with other immunoglobulin G1 monoclonal antibodies (IgG1 mAbs), with low systemic clearance (0.334 L/day), low volume of distribution (3.9 L for central compartment and 4.2 L for peripheral compartment), and long elimination half-life (19.9 days). 4,5 Model-predicted mean (± standard deviation) steady-state area under the concentration curve (AUCss), peak (Cmax,ss), and trough (Cmin,ss) concentrations in TED patients were 131 (± 30.9) mg∙hr/mL, 643 (± 130) µg/mL and 157 (± 50.6) µg/mL, respectively, suggesting low inter-subject variability.Population PK analysis indicated no significant impact of baseline age, gender, race, weight, smoking status, renal impairment (mild/moderate), and hepatic function (total bilirubin, aspartate and alanine aminotransferases) on teprotumumab PK. Female patients had 15% higher Cmax,ss but similar AUC compared to male patients, which is not considered clinically relevant.Exposure-response analysis from the TED dose regimen indicated no meaningful correlations between exposures (AUCss, Cmax,ss and Cmin,ss) and key efficacy endpoints or selected safety variables, supporting the demonstrated, favorable benefit-risk profile of the TED dose regimen.2 Conclusion: Teprotumumab PK was characterized in TED patients by long elimination half-life, low systemic clearance and low volume of distribution, consistent with other IgG1 mAbs. There was no meaningful exposure-response relationship at the selected TED dose regimen for both efficacy and safety endpoints, supporting the teprotumumab dose regimen used in TED patients. Reference: (1) Smith TJ, et al. N Engl J Med 2017;376:1748-1761. (2) Douglas RS, et al. AACE 2019 late-breaking abstract. (3) ClinicalTrials.gov: NCT00400361. (4) Dirks NL et al. Clin Pharmacokinet. 2010;49(10):633-59. (5) Ryman JT et al. CPT Pharmacometrics Syst Pharmacol. 2017;6(9):576-88.

Analisa Tingkat Kepuasan Pengguna Kereta Api Kota Padang

The problem that often occurs in cities is structuring the city, starting with settlements, spatial planning, poor communities and transportation, as well as the city of Padang. The increasing number of people needing transportation, especially the destination of Padang-Minangkabau International Airport, is one of the reasons for the opening of the train station. Because the train has several advantages compared to other land transportation equipment, which are relatively cheap costs, can sit freely, faster,and safer. The purpose of this study was to determine how much public interest in railroad modes of transportation by analyzing the level of satisfaction of train users in accordance with the response from the public.The Coefficient of Determination (R2) is obtained from the Adjusted R Square number of 0.404. This shows that the contribution of variables of comfort, safety, safety, time, transportation rates, and service to the users of the Padang-Minangkabau International Airport train are 0.404 or 40.4% while the remaining 59.6% is influenced by other variables not examined in this study. From this result, get a value of 40.4% which indicates that the services provided by PT. Kereta Api Indonesia has not been good and users have not been satisfied with the performance of the Padang-Minangkabau International Airport train service

The Effect of Price, Ease of Transaction, Information Quality, Safety, and Trust on Online Purchase Decision

This research aims to analyze the effect of price, ease of transaction, information quality, safety, and trust on online purchase decision. Applying purposive sampling technique, the sample was students of the Department of Management, Faculty of Economics and Business, University of Jember that consisted of 100 respondents. This study used quantitative data sourced from primary data. Data were analyzed using multiple linear regression. Results showed that, both partially and simultaneously, the variables of price, ease, information quality, safety, and trust had a significant positive effect on online purchase decision.

Effectiveness and safety of direct-acting antivirals in hepatitis C infected patients with mental disorders: Results in real clinical practice.

The aim of this study is to analyze the effectiveness and safety of direct-acting antivirals (DAAs) in psychiatric patients with chronic hepatitis C (CHC). Secondary objectives included adherence and drug-drug interaction (DDIs) evaluations. Prospective observational comparative study carried out during 3 years. Psychiatric patients were included and mental illness classified by a psychiatric team based on clinical records. Main effectiveness and safety variables were sustained virologic response (SVR) at posttreatment week 12 (SVR12) and rate of on-treatment serious drug-related adverse events (AEs), respectively. A total of 242 psychiatric and 900 nonpsychiatric patients were included. SVR12 by intention-to-treat (ITT) analysis of psychiatric vs nonpsychiatric patients was 92.6% (95% confidence interval [CI], 89.1-96.1) vs 96.2% (95% CI, 94.9-97.5) (P = .02). SVR12 by modified-ITT analysis was 97.8% (95% CI, 95.0-99.3) vs 98.4% (95% CI, 97.5-99.3) (P = .74). 92.2% of psychiatric patients with mental disorders secondary to multiple drug use (MDSDU) and 93.0% of psychiatric patients without MDSDU vs 96.2% of nonpsychiatric patients reached SVR12 (P = .05 and P = .20, respectively). The percentage of adherent patients to DAAs did not show differences between cohorts (P = .08). 30.2% of psychiatric patients and 27.6% of nonpsychiatric patients presented clinically relevant DDIs (P = .47). 1.7% vs 0.8% of psychiatric vs nonpsychiatric patients developed serious AEs (P = .39); no serious psychiatric AEs were present. DAAs have shown a slightly lower effectiveness in psychiatric patients with CHC, as a result of loss of follow up, which justifies the need for integrated and multidisciplinary health care teams. DAAs safety, adherence, and DDIs, however, are similar to that of nonpsychiatric patients.

Subjective Well-Being of Portuguese Employees: The Role of Personality and Organizational Context

Subjective well-being (SWB) has been widely associated with quality of life and health outcomes. In the organizational and work context, SWB has been also related to better outcomes, like higher levels of job satisfaction, productivity and enhanced career development. Yet in the present context of economic pressure and highly dynamic work markets employees are asked to be better at taking risks to come with fast and creative solutions and companies are facing the challenge of recruiting best equipped individuals and assuring the conditions for them to be at their best. Personal and organizational characteristics, like personality and psychological safety seen to play an important role in these matters. However, it is still to know how are these variables associated with the employees’ well-being. The aim of this study is to explore the impact of open to experience, resilience and psychological security on SWB. A sample of 193 Portuguese adults working in 20 companies of the industry and IT sectors answered a standardize questionnaire. In order to explore what and to what extent personal (open to experience and resilience) and organizational (psychological safety) variables impact SWB the multiple regression models were computed. Results showed that the most associated variable in the three models is resilience and that the three predictors have higher impact on explaining Life Satisfaction (29.5%) and Positive Affect (26.5%).

Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma

SummaryPurpose Galunisertib, a TGF-β inhibitor, has demonstrated antitumor effects in preclinical and radiographic responses in some patients with malignant glioma. This Phase 1b/2a trial investigated the clinical benefit of combining galunisertib with temozolomide-based radiochemotherapy (TMZ/RTX) in patients with newly diagnosed malignant glioma (NCT01220271). Methods This is an open-label, 2-arm Phase 1b/2a study (N = 56) of galunisertib (intermittent dosing: 14 days on/14 days off per cycle of 28 days) in combination with TMZ/RTX (n = 40), versus a control arm (TMZ/RTX, n = 16). The primary objective of Phase 1b was to determine the safe and tolerable Phase 2 dose of galunisertib. The primary objective of Phase 2a was to confirm the tolerability and pharmacodynamic profile of galunisertib with TMZ/RTX, and the secondary objectives included determining the efficacy and pharmacokinetic (PK) profile of galunisertib with TMZ/RTX in patients with glioblastoma. This study also characterized the changes in the major T-cell subsets during TMZ/RTX plus galunisertib treatment. Results In the Phase 2a study, efficacy results for patients treated with galunisertib plus TMZ/RTX or TMZ/RTX were: median overall survival (18.2 vs 17.9 months), median progression-free survival (7.6 vs 11.5 months), and disease control rate (80% [32/40] vs 56% [9/16] patients) respectively. PK profile of galunisertib plus TMZ/RTX regimen was consistent with previously published PK data of galunisertib. The overall safety profile across treatment arms was comparable. Conclusion No differences in efficacy, safety or pharmacokinetic variables were observed between the two treatment arms.

Single-session treatment of benign thyroid nodules with radiofrequency ablation: Results at 6 months in 24 patients

ObjectiveTo evaluate the efficacy and safety of one single-session of radiofrequency ablation (RFA) performed in thyroid benign and predominantly solid nodules. Patients and methodsUnicentric retrospective study in usual clinical setting that included patients with solid and benign thyroid nodules treated with one single session of RFA and with follow-up of at at least 6 months after the procedure. RFA was performed as an alternative to surgery in cases of pressure symptoms or nodular growth evidence. Patients were evaluated basally and at one, 3 and 6 months after RFA and also at twelve months if the follow-up was available. In each evaluation efficacy variables were recorded (percentual change from basal volume, percentage of nodules reaching a volume reduction above 50% from baseline, patients with disappearance of pressure symptoms and the possibility of antithyroid drug withdrawal) and safety variables were also registered including minor complications (pain needing analgesic drugs, hematoma) and major complications (voice changes, braquial plexus injury, nodule rupture and thyroid dysfunction). Results24 patients with a follow-up of at least 6 months after RFA were included, 16 of them with more than 12 months of follow-up. Mean nodule volume changed from 25.4 ± 15.5 ml basally to 10.7 ± 9.9 ml at month 6 (p < 0,05) and to 9.9 ± 10,4 ml at month 12 in 16 nodules. 6 months after RFA mean volumetric reduction was 57.5 ± 24% and 65% of the nodules reached a volume reduction above 50% from baseline. Median percentage of reduction at month 6 was 50.4 ± 25.7% for nodules with a basal volume above 20 ml (n = 13) and 65.3 ± 20.1% for nodules with a lower basal volume (n = 11). Pressure symptoms reported in 12 patients disappeared in all cases. Antithyroid drugs could be stopped in 3 of 4 cases treated before RFA. A mild and transient pain responsive to conventional analgesic drugs was recorded in 9 patients during the 24 h after the procedure and in 7 a small perithyroid and transient hematoma was observed in the 48 following hours. One major complication was described as a nodule rupture that recovered spontaneously. There were no changes in hormonal values in euthyroid cases. ConclusionA single session of RFA seems to be an effective and safe procedure in patients with solid thyroid nodules with pressure symptoms or relevant growth evidence. As an outpatient and scarless procedure with no need of general anaesthesia it could become an useful alternative to lobectomy when surgery is refused or in patients at high surgical risk.

IMPLEMENTASI PROGRAM KESELAMATAN DAN KESEHATAN KERJA TERHADAP PRODUKTIVITAS TENAGA KESEHATAN PADA RSUD dr. SAYIDIMAN MAGETAN

Abstract should The purpose of this study was to determine whether there is an influence of the application of occupational safety and health to the productivity of health staff at RSUD dr. Sayidiman Magetan. The data used in this study were obtained from a questionnaire (primary) and several observations and direct interviews with health staff at RSUD dr. Sayidiman Magetan. The analysis technique used is multiple regression analysis using the hypothesis test, namely the F test and the T test. This research will later be used as one of the scientific developments in the field of management, especially in the field of human resources. From this study it can be concluded based on statistical tests that overall occupational safety and health variables (simultaneous-F tests) have a positive effect on the productivity variables of health workers.

IMPLEMENTASI PROGRAM KESELAMATAN DAN KESEHATAN KERJA TERHADAP PRODUKTIVITAS TENAGA KESEHATAN PADA RSUD dr. SAYIDIMAN MAGETAN

Abstract should The purpose of this study was to determine whether there is an influence of the application of occupational safety and health to the productivity of health staff at RSUD dr. Sayidiman Magetan. The data used in this study were obtained from a questionnaire (primary) and several observations and direct interviews with health staff at RSUD dr. Sayidiman Magetan. The analysis technique used is multiple regression analysis using the hypothesis test, namely the F test and the T test. This research will later be used as one of the scientific developments in the field of management, especially in the field of human resources. From this study it can be concluded based on statistical tests that overall occupational safety and health variables (simultaneous-F tests) have a positive effect on the productivity variables of health workers.