Safety Variables Research Articles

A 3-year prospective study of a multidisciplinary early proactive therapeutic drug monitoring programme of infliximab treatments in inflammatory bowel disease.

Therapeutic drug monitoring (TDM) of trough serum infliximab concentrations has been mainly used in case of loss of response in patients with inflammatory bowel disease (IBD). The aim of this study was to evaluate the effectiveness and safety of a multidisciplinary early proactive TDM (mep-TDM) programme for dose adjustment. A 3-year prospective study was conducted based on a sample of 81 patients who started treatment and were subsequently subjected to mep-TDM with the first control at week 14. Data of a historical control group of 72 patients treated with infliximab and managed with empirical dosing were included. Effectiveness variables were treatment failure, IBD-related surgery and IBD-related hospitalization. Safety variables were serious infusion reactions (SIRs) and adverse reactions. Cox regression was used for survival analysis. In the mep-TDM study group, compared to the control group, there was a significant reduction in the risk of treatment failure (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.27-0.92; P = .037), IBD-related surgery (HR: 0.14; 95% CI: 0.03-0.65; P = .012) and hospitalization (HR: 0.38; 95% CI: 0.17-0.87; P = .022). SIRs were lower in the mep-TDM group (2.5% vs 10.4%; P < .050); the incidence of adverse reactions was similar (3.7% vs 3.9%; p > .999). This study found that compared to empirical dosing, mep-TDM is associated with improved efficacy and safety of infliximab therapy, reduced IBD-related hospitalization and surgery and incidence of SIRs, and increasing long-term durability of treatment effects.

Effect of Seasonality on the Quantiles Estimation of Maximum Floodwater Levels in a Reservoir and Maximum Outflows

Certain relevant variables for dam safety and downstream safety assessments are analyzed using a stochastic approach. In particular, a method to estimate quantiles of maximum outflow in a dam spillway and maximum water level reached in the reservoir during a flood event is presented. The hydrological system analyzed herein is a small mountain catchment in north Spain, whose main river is a tributary of Ebro river. The ancient Foradada dam is located in this catchment. This dam has no gates, so that flood routing operation results from simple consideration of fixed crest spillway hydraulics. In such case, both mentioned variables (maximum outflow and maximum reservoir water level) are basically derived variables that depend on flood hydrograph characteristics and the reservoir’s initial water level. A Monte Carlo approach is performed to generate very large samples of synthetic hydrographs and previous reservoir levels. The use of extreme value copulas allows the ensembles to preserve statistical properties of historical samples and the observed empirical correlations. Apart from the classical approach based on annual periods, the modelling strategy is also applied differentiating two subperiods or seasons (i.e., summer and winter). This allows to quantify the return period distortion introduced when seasonality is ignored in the statistical analysis of the two relevant variables selected for hydrological risk assessment. Results indicate significant deviations for return periods over 125 years. For the analyzed case study, ignoring seasonal statistics and trends, yields to maximum outflows underestimation of 18% for T = 500 years and 29% for T = 1000 years were obtained.

Effectiveness and safety of sofosbuvir/velpatasvir ± ribavirin vs glecaprevir/pibrentasvir in genotype 3 hepatitis C virus infected patients

ObjectivesSofosbuvir/velpatasvir±ribavirin (SOF/VEL±RBV) and glecaprevir/pibrentasvir (GLE/PIB) are the drug combinations of choice for treating individuals with genotype 3 hepatitis C virus (G3-HCV) infection. The objective of this study was to evaluate...

Systematic review and meta-analysis of safety and efficacy of high-intensity focused ultrasound (HIFU) for face and neck rejuvenation.

High-intensity focused ultrasound (HIFU) is widely used for skin rejuvenation and tightening. The aim of this study was to determine the safety and efficacy of HIFU for face and neck rejuvenation. A systematic search of peer reviewed articles published before December 2017 was performed using Medline, Web of Science, and Scopus databases. Retrieved studies were screened, and clinical trials or follow-up studies which were evaluated the effect of HIFU on rejuvenation treatments of face and neck area were included. Risk of bias for each study was assessed and was reported. Safety and efficacy variables, which were reported more often in papers, were included in meta-analysis. Seventeen studies involving 477 participants were included in the analysis. Meta-analysis showed moderate improvement as scores of 2.74 (95% CI 2.06-3.43) and 2.68 (95% CI 1.92-3.45), out of 5 maximum score, for objective improvement score and subjective satisfaction score, respectively. Meta-analysis of mean pain score, assessed by a 0-10 Likert score, was 4.2 (95% CI 4.27-5.19). Edema and erythema showed considerable heterogeneity, and no hyperpigmentation was reported by included studies. Included studies used multiple and different outcome variables with different scoring at various time points. Long follow-up was not reported by majority of studies. HIFU is safe procedure in short term and has a moderate effect on rejuvenation of face and neck areas.

Assessing factors affecting safety violations of bus rapid transit drivers in the Greater Jakarta Area

Instead of human factors, organization and environmental factors were the primary cause of traffic accidents in public transportation. This study confirmed the causal relationships between safety variables that influenced the safety violation carried out by professional bus rapid transit (BRT) drivers in the Greater Jakarta Area based on sufficient theoretical and empirical support. The influences of latent safety variables that indicated quality, such as safety climate, safety awareness, safety behavior, safety motivation, safety participation, safety knowledge, and safety violation, were examined using a questionnaire. 391 Transjakarta drivers participated from both a private operator company and a local government-owned operator company. The response rate for this study was 78.2%. A partial least square – structural equation modeling (PLS-SEM) approach was conducted to test the hypothetical model. The results suggested that improving the safety climate would increase the motivation of the driver to pursue safety. Increased safety motivation would improve safety behavior, and finally, would reduce the tendency for a safety violation. Increasing the safety climate would also increase safety knowledge. Safety knowledge would make drivers more likely to participate and care for safety improvement, and finally, safety violations would be reduced. The moderating effect of a safety climate had a significant causal relationship on safety violations. Thus, the difference in the treatment of drivers by BRT operator companies in Jakarta influenced the potential safety violations by the drivers.

Abstract TMP88: Blood Pressure Variability Within 24 Hours After Recanalization Worsens Functional Outcome Among Patients Who Underwent Endovascular Treatment

Introduction: Systemic blood pressure (BP) should be strictly monitored and adjusted during the initial stages of stroke. Due to the impairment of cerebral autoregulation, cerebral blood flow is directly affected by systemic BP and some degree of permissive hypertension might be beneficial prior to reperfusion treatments to ensure an adequate perfusion in the ischemic tissue. However, after generalization of endovascular treatment (EVT) the rate of successful recanalization has skyrocketed and it is not well established if, once achieved, BP control should be stricter given its potential risks. We aim to explore the relation between BP and outcome among patients who underwent EVT. Methods: This is a retrospective study of a prospectively acquired unicentric database that includes patients who underwent EVT with successful recanalization measured by a mTICI ≥2b. Hourly measuring of systolic and diastolic BP was conducted during the first 24 hours post-procedure. BP variation was measured using standard deviation (SD) and range. We explored the effects of BP on functional outcome at 3 months and safety variables. Results: The study included 351 subjects with a mean age of 72.7+/-13.1 and 51.6% were men. The 3-months mRS was ≤2 in 50.4% of patients, 66 subjects (19.2%) presented hemorrhagic transformation and 67 (19.1%) were dead in the 3-months follow-up period. Both systolic BP SD (15.6+/-9.9 vs. 12.9+/-4.3; p&lt;0.01) and range (55.6+/-18.4 vs. 48.7+/-16.4; p&lt;0.01) were higher among patients with bad functional outcome (mRS&gt;2). Subjects with hemorrhagic transformation presented higher range of DBP (35.7+/-12.4 vs. 32.0+/-11.9; p=0.03) and SBP (56.8+/-17.0 vs. 51.4+/-18.1; p=0.03) and higher diastolic DBP SD (9.3+/-4.1 vs. 8.2+/-2.7; p&lt;0.01). In a logistic regression analysis DBP SD predicted ICH (OR 1.11, CI 1.02-1.22, p=0.01) and SBP range emerged as a predictor of poor functional outcome (OR 0.97, CI 0.96-0.99, p&lt;0.01). No differences were detected in regard to admission BP, maximal and minimal BP or mean arterial pressure. Conclusions: Major fluctuations in systolic and diastolic BP predict increased risk of hemorrhagic complications and poor functional outcome. Minimizing BP fluctuations may improve outcome of EVT patients after recanalization.

Abstract 146: Time Matters: Adjusted Analysis of the Influence of Direct Transfer to Angio-Suite Protocol in Functional Outcome

Direct transfer to angio suite (DTAS) protocol is a promising measure to improve onset to recanalization time in patients who undergo endovascular treatment. The association of different time windows with prognosis in this population is influenced by several factors. We aim to analyze the influence of DTAS in clinical and functional outcome depending on time from symptom onset to treatment. Methods: Retrospective case-control study of 174 consecutive DTAS cases matched with 175 patients initially transferred to CT (DTCT) from February 2016 to April 2019. To obtain comparable groups on admission, cases and controls were matched by occlusion location, age (±2 years), baseline NIHSS score (±2 points) and time from symptoms onset to hospital arrival (±30 minutes). We analyzed the rate of good functional outcome at 3 months (mRS 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, gender or baseline NIHSS score (table 1). Median door-to-groin time was shorter in the DTAS patients (16 (13-21) minutes Vs 70 (41.5-98.5); p&lt;0.01). DTAS patients presented lower NIHSS score at 24 hours 9 (3.5-17) Vs 14 (5-19); p=0.01) and a lower rate of symptomatic hemorrhagic transformation (4.6% versus 10.9%, p&lt;0.03). At 90 days, DTAS patients had a higher rate of good functional outcome (43% versus 29%; OR 1.81, 95% CI, 1.14-2.87; p=0.01). In multivariate analysis adjusted by confounding factors, better outcome in DTAS was observed in patients admitted in the 0-3 hours form onset window (n=156, OR 2.63, 95%CI: 1.31-5.28; p&lt;0.01), but not in patients admitted in the 3-6 hours window (n=193, OR 1.37 955CI:0.72-2.60, p=0.2). Conclusion: 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 Occupational Safety And Health On Performance An Empirical Investigation

Employees are important assets of the organization, so many things that need to be considered related to improving performance. An employee's performance will be in accordance with the wishes of the company if the quality of human resources is good. Good performance can also be supported by the presence of occupational safety and health guarantees from the company. The Implementation of the Occupational Safety and Health (OSH) system also influences employee performance. This study aims to determine the effect of Occupational Safety and Health (OSH) on the performance of midwives at the XYZ Islamic Hospital Fetomatenal Installation Riau Province, Indonesia. The results of analyze of primary data using SPSS Version 23, it can be concluded that the work safety variable has a significant effect on performance, knowing that occupational health variables have a significant effect on performance. In addition, it can be concluded that occupational safety and health variables together have a significant influence on performance variables. DOI: https://doi.org/10.5281/zenodo.3672395

PENGARUH MANFAAT, KEMUDAHAN DAN KEAMANAN TERHADAP MINAT PEMAKAIAN FINANCIAL TECHNOLOGY PADA APLIKASI OVO SEBAGAI DIGITAL PAYMENT (Study Kasus Mahasiswa FEB Universitas Muhammadiyah Metro)

This study aims to obtain data and find out the positive effect of benefits, convenience and security onthe interest in using financial technology in OVO applications as a digital payment study in the case of FEBstudents at the Muhammadiyah Metro University. With the technique of sampling, namely with accedentalsampling with a sampling time of 30 days to get as many as 68 samples. In this study the method used is libearyresearch and field research, namely library research, observation, interviews, correspondence, andquestionnaires. In this study the analytical tool used is multiple linear regression analysis, to determine thedependent and independent variables with the SPSS V16 For Windows program. The results of researchconducted by researchers show that there is an influence on the benefits, convenience and security of the interestin using financial technology in OVO applications as digital payments, based on the analysis results, the dataobtained is Fcount 130,280 &gt; 2.75 and is shown by linear regression with the coefficient of determination (R2)0.859 which means that the interest in financial use in OVO applications is influenced by the benefits,convenience and safety variables of 85.9% and the remaining 14.1% is influenced by other factors outside thisstudy.

Incorporating safety reliability into route choice model: Heterogeneous crash risk aversions

In this study, a route choice model which accounts for both travelers’ safety concern—route safety reliability—and travel time concern is proposed. Route safety reliability (variability) is defined by the distribution of the travel crash risk cost (CRC) to represent the safety condition of travel routes. We further associate the travel safety variability due to stochastic crash occurrence with travelers’ crash risk aversion route choice behaviors, and postulate that travelers acquire the variability of route travel safety based on the past experience and factor it into their route choice in the form of an effective crash risk cost (effective CRC). This effective crash cost is formed depending on travelers’ requirements on safe arrivals, and thus varies with individuals and trip specific factors (e.g. purposes). Moreover, all travelers want to minimize the summing of their travel time and their effective CRC. A route-based solution algorithm is designed to solve the route choice model. Two networks including Nguyen and Dupis’ network and Sioux falls network are conducted as numerical studies to illustrate the model. The results show that (1) the travelers’ route choice behaviors are sensitive to the route safety performance, including the average safety condition (the mean of the CRC distribution) and safety reliability (the standard deviation of the CRC distribution); (2) the safety performance of movements at intersection would significantly influence the travelers’ route choice decisions; and (3) travelers with different safety attitudes (heterogeneous crash risk aversions) would make different route choice decisions.

Safety and Efficacy of a New Synthetic Material Based on Monetite, Silica Gel, PS-Wallastonite, and a Hydroxyapatite Calcium Deficient: A Randomized Comparative Clinic Trial.

Background and Objectives: Maxillary bone defects related to post-extraction alveolar ridge resorption are usual. These defects may lead to failure in further surgical implant phases given the lack of bone volume to perform the dental implant. The objective of this clinical assay was to evaluate the safety and efficacy of an experimental synthetic bone substitute in the preservation of post-extraction maxillary alveoli. Materials and Methods: 33 voluntary patients who had at least one maxillary premolar tooth that was a candidate for exodontia (n = 39) and subsequent implant rehabilitation participated. The regenerated alveoli were monitored by means of periodic clinical examinations (days 9 ± 1, 21 ± 4, 42 ± 6, and 84 ± 6), measuring the height and width of the alveolar crest (days 0 and 180 ± 5), measurement of radiodensity using tomographic techniques (days 0–5 and 175 ± 5), and histological examination of biopsies collected at 180 ± 5 days. Results: No significant differences were observed during the entire follow-up period between the two groups with respect to the safety variables studied. A variation in width of −0.9 ± 1.3 mm and −0.6 ± 1.5 mm, and a variation in height of −0.1 ± 0.9 mm and −0.3 ± 0.7 mm was observed for experimental material Sil-Oss® and Bio-Oss®, respectively. The radiodensity of the alveoli regenerated with the experimental material was significantly lower than that corresponding to Bio-Oss®. However, the histological study showed greater osteoid matrix and replacement of the material with newformed bone in the implanted beds with the experimental material. Conclusions: Both materials can be used safely and proved equally effective in maintaining alveolar flange dimensions, they are also histologically biocompatible, bioactive and osteoconductive. The experimental material showed the advantage of being resorbable and replaced with newformed bone, in addition to promoting bone regeneration.

Satisfaction and adherence with glatiramer acetate 40mg/mL TIW in RRMS after 12 months, and the effect of switching from 20mg/mL QD

BackgroundPatient satisfaction with treatment in relapsing-remitting multiple sclerosis (RRMS) has a direct impact on adherence to treatment and, consequently, upon treatment outcomes and costs. Patient-reported outcomes (PROs) are a common method for determining patient satisfaction in MS and other diseases. MethodsThe 12-month, open-label, Phase IV CONFIDENCE study assessed patient satisfaction and treatment adherence, using PROs, as well as safety outcomes in patients with RRMS treated with glatiramer acetate (GA). In the previously reported (Cutter et al., 2019) initial 6-month core phase of the study, patients were randomized to receive three-times-weekly (TIW) GA 40 mg/mL (GA40; n = 431) or once-daily GA 20 mg/mL (GA20; n = 430). In the 6-month, single-arm extension phase, 789 patients completing the core phase were treated with GA40 to determine whether benefits observed in the core phase were sustained during the extension phase, to ascertain if switching from GA20 to GA40 resulted in PRO changes, and to assess safety outcomes. ResultsSuperior PRO scores for patient satisfaction with treatment, patient perception of treatment convenience, and symptomatic changes (fatigue impact and mental health) observed in the GA40 group versus the GA20 group in the core phase were all maintained in the extension phase. Treatment adherence, significantly greater in the GA40 versus the GA20 group in the core phase, was sustained in patients continuing to receive GA40 in the extension phase, while those who switched from GA20 to GA40 increased their adherence during the extension phase. Safety variables remained consistent throughout the study, with no notable changes observed in patients switching from GA20 to GA40. ConclusionsData from the extension phase of the CONFIDENCE study show that the benefits associated with GA40 treatment in terms of medication satisfaction, treatment convenience perception, symptomatic changes in fatigue impact and mental health status, and treatment adherence were maintained over a 12-month observation period. These results confirm the preferential utility of GA40 versus GA20 in clinical practice, with no additional safety concerns associated with switching from GA20 to GA40.

Factors Influencing the User Acceptance of Automated Vehicles Based on Vehicle-Road Collaboration

The development of smart highway and vehicle-road collaboration has stimulated the market applications of automated vehicles. However, consumer acceptance of automated vehicles will influence the time course of automated driving technology promotion. This research explores user acceptance and demand for automated vehicles based on vehicle-road collaboration and identifies which factors drive the acceptance of automated vehicles. A sample of 3900 questionnaires are obtained through classification sampling. The descriptive statistical analysis of 3594 effective multi-source sample data shows that the user acceptance of automated vehicles based on the vehicle-road collaborative environment is 70.94%. The results show that the five categories of groups have significant differences in the acceptance of automated vehicles, and the focus on individual variables is higher than the overall acceptance. Due to the contradiction and dependence among various variables, multiple regression analysis is introduced. The results show that the six variables of safety, practicability, economy, highly automated driving functions, vehicle-road collaborative fusion application, and after-sale service have a significant positive impact on the acceptance of automated vehicles. The reasons why these six factors affect user acceptance are then analyzed in depth. The fitting model and acceptance value range obtained by this research can be used for market research. The research findings provide data support and theoretical reference for the research and development, marketing, teaching, and servicing of autonomous driving technology.

Impacts of Occupational Cognitive Failure and Subjective Workload on Patient Safety Incidents among Intensive Care Units Nurses.

Background:Life-saving treatments and high-quality care techniques increase the opportunity for patient safety incidents in Intensive care unit.Aims:This descriptive correlation study aimed to determine the impacts of occupational cognitive failure and subjective workload on patient safety incidents among intensive care units nurses.Methods and Material:One hundred seventy-six nurses working in intensive care units were included using census sampling. The data collection tools consisted of demographic and occupational data, standard questionnaires of subjective workload (NASA-TLX) and occupational cognitive failure (OCFQ), and a question about frequency of patient safety incidents. Data analysis was performed using Mann–Whitney and Kruskal–Wallis, Spearman rank correlation coefficient, and logistic regression tests.Results:Occupational cognitive failure (OR = 1.043), subjective workload in dimension of “performance” (OR = 0.982), age (OR = 0.947), and gender (OR = 3.726) were important predictive variables of patient safety incidents.Conclusions:Nursing mangers and policymakers can consider the factors identified for staffing nurses and development of patient safety programs.

Patient safety in graduate curricula and training needs of health workforce in India: A mixed-methods study

Improving quality of health services and providing safe care require well-trained and skilled workforce. The inclusion of components of patient safety in graduate training curricula, followed by adherence to curricula in teaching programs, can improve the quality of health-care services. To review the existing training curricula for five subgroups of health workforce (Allopathic doctors, nurses, laboratory technicians, pharmacists, and nurse midwives) and to document the components and identified variables of patient safety covered. A mixed-methods study was conducted during July 2017-March 2018. Data were collected through desk review, field visits, in-depth interviews, self-administered questionnaires, and focused group discussions (FGDs). A total of 24 variables were identified by the experts to review the training curricula. Seven states, 28 institutes, and 42 health-care facilities were visited. A total of 516 staff from different health cadres participated in the study through 54 interviews, 156 self-administered questionnaires, and 24 FGDs. Of 24 patient safety variables considered, 16 were covered in the medical and nursing, 9 in laboratory technician and pharmacist, and 5 in midwives' curricula. The teaching material on the patient safety, for most categories of staff, was not available in consolidated form, and there was no standardization. There is a need for the development of comprehensive training material cum operational modules on patient safety, suitably adopted as per the learning needs of different subgroups of health staff. The need for strengthening patient safety has been further underscored as the health workforce is fighting the coronavirus disease 19 (COVID-19) pandemic. The initiatives on patient safety will contribute to improved overall quality of health services, which in turn would advance universal health coverage.

Operating Risk (Cost-Volume-Profit) and Economic Value Added (EVA®)

Today, it is unquestionable the importance that organizational management is supported by indicators. Also, knowledge of value creation and operating risk are information that differentiates this management support. This study aimed to verify the relationship between the value creation generated by companies included in the sample and the indicators used in operating risk (cost-volume-profit analysis). In the literature review the concept of value creation and the indicators usually used to measure operating risk, break-even point, margin of safety, and degree of operating leverage, were presented and characterized, as well as the Economic Value Added (EVA®), which was the value-based performance measure used in the study. The sample consists of 27 non-financial companies listed in Euronext Lisbon and the period analyzed was the one between 2014 and 2018. The data were obtained through the consolidated annual accounts of the sample companies, and its analysis was performed using the multivariate statistical analysis technique, linear regression. The results showed that the estimated multiple linear regression model allowed, with a very reasonable quality, to estimate the impact that the break-even point and the margin of safety variables have on the variation of the value of EVA®. This study gives significant information showing how operating risk indicators affect value creation, which is considered one the main objectives of companies.

Seguridad y efectividad de la reconstrucción mamaria en pacientes anticoaguladas

ObjectiveTo study the safety and effectiveness of post-mastectomy breast reconstruction (PBR) in patients receiving chronic anticoagulation. Patients and methodsRetrospective case-control study in anticoagulated patients undergoing PBR in our centre between January 2011 and December 2015. Safety variables consisted of the development of hematoma, infection, seroma, skin necrosis, wound dehiscence, thrombosis, cancer recurrence, need for blood transfusion, and hospital stay. Effectiveness variables consisted of reintervention due to complications, surgical rescue and loss of reconstruction, and abandonment of reconstructive intent. Patients were matched 3:1 with a control group of patients not receiving anticoagulation but who were similar in age, body mass index, smoking, radiotherapy, timing of reconstruction, type of reconstruction, laterality and symmetry procedure. ResultsThere were 7 cases and 21 controls. Anticoagulated patients showed a higher frequency of hematoma than patients not receiving anticoagulation (42.9% versus 4.8%, p=0.038), infection (57.1% versus 14.3%, p=0.043), blood transfusion (42.9% versus 0%, p=0.011), OR 1.75, 95% CI (0.921-3.324), and prolonged hospital stay of a median of 9 days, interquartile range (IQR) 8-20 versus 7, IQR 5-9 (p=0.015). PBR was successful in 71.4% of anticoagulated patients and in 95.2% of the control group. ConclusionsThis study confirms that PBR is significantly less safe in anticoagulated patients at high thromboembolic risk and is also less effective, although this difference was not statistically significant. These results could be considered when advising patients on the decision to undergo PBR.

ANALISIS FAKTOR MOTIVASI KERJA KARYAWAN (Studi Kasus pada PT Orela Shipyard)

PT Orela Shipyard is a family company running the shipping industry. In the two recent years, the company’s turnover becomes fluctuated, this change is caused by some factors, one of them is the employee work motivation. The purpose of this research is to find out the factors that motivate the employee works of PT Orela Shipyard. The data used are primary data with data collection techniques by using a questionnaire.The sample that is used is 60 employees of PT Orela Shipyard that consist of 30 office employees and 30 shipyard employees with a simple random sampling technique and that are processed by using SmartPLS 3.0 software program. This research uses a first-order construct and second-order construct tests. The results of this research indicate that the variables of work safety, award, achievement, salary, relationship with superiors and work conditions are the factors that motivate the work of the employees at PT Orela Shipyard.

A Bayesian adaptive design for addressing correlated late-onset outcomes in phase I/II randomized trials of drug combinations in oncology

An advantage of phase I/II clinical trials for anticancer drugs is that safety and efficacy can be simultaneously evaluated in a single study. However, in order to benefit from this advantage, it is necessary for the safety and efficacy variables to comprise late-onset outcomes. In addition, current cancer treatments often involve therapies combining multiple drugs. Consequently, increasing emphasis has been placed on the importance of randomized clinical trials, which randomize the drugs being tested. This study proposes specific methods for addressing late-onset outcomes for safety and efficacy in phase I/II randomized trials of anticancer drug combinations. Data from patients in cases where the evaluation of safety and efficacy is not complete are considered missing data. A model taking into consideration the missing data mechanism, relationship between safety and efficacy, and correlation between observation points was used to adaptively determine the dose combination to assign to the next cohort. Simulation studies suggested that the proposed method is capable of supporting clinical trials in practice with realistic study periods. We believe the proposed method may flexibly adapt to practical requirements and contribute to advances in drug development.

Topical Agents for the Treatment of Atopic Dermatitis

Approval of the new topical phosphodiesterase 4 inhibitor crisaborole ointment, 2%, to treat mild-to-moderate atopic dermatitis (AD) warrants careful consideration of available efficacy and safety data for topical therapies to contribute to a better understanding of the role of crisaborole in the treatment of mild-to-moderate AD. A literature review was conducted to identify results of randomized, blinded, vehicle-controlled trials of topical agents for the treatment of AD published from January 1, 1997 to April 30, 2018. This review summarizes the efficacy and safety data of topical therapies including corticosteroids, calcineurin inhibitors, and crisaborole and it shows that comparison among available agents is difficult because of differing methodologies used across clinical trials and that there is considerable variability in safety reporting among AD trials. Published clinical studies for crisaborole demonstrate its efficacy and manageable safety profile. J Drugs Dermatol. 2020;19(1):50-64. doi:10.36849/JDD.2020.4508