Improve Success Rates Research Articles

Does biomarker use in oncology improve clinical trial failure risk? A large-scale analysis.

PurposeTo date there has not been an extensive analysis of the outcomes of biomarker use in oncology.MethodsData were pooled across four indications in oncology drawing upon trial outcomes from www.clinicaltrials.gov: breast cancer, non‐small cell lung cancer (NSCLC), melanoma and colorectal cancer from 1998 to 2017. We compared the likelihood drugs would progress through the stages of clinical trial testing to approval based on biomarker status. This was done with multi‐state Markov models, tools that describe the stochastic process in which subjects move among a finite number of states.ResultsOver 10000 trials were screened, which yielded 745 drugs. The inclusion of biomarker status as a covariate significantly improved the fit of the Markov model in describing the drug trajectories through clinical trial testing stages. Hazard ratios based on the Markov models revealed the likelihood of drug approval with biomarkers having nearly a fivefold increase for all indications combined. A 12, 8 and 7‐fold hazard ratio was observed for breast cancer, melanoma and NSCLC, respectively. Markov models with exploratory biomarkers outperformed Markov models with no biomarkers.ConclusionThis is the first systematic statistical evidence that biomarkers clearly increase clinical trial success rates in three different indications in oncology. Also, exploratory biomarkers, long before they are properly validated, appear to improve success rates in oncology. This supports early and aggressive adoption of biomarkers in oncology clinical trials.

External cephalic version - A 10-year review of practice

IntroductionFollowing the term breech trial (TBT), the incidence of Caesarean section secondary to breech presentations increased, from 76.9 % to 89.7 %. External Cephalic Version (ECV) is a safe effective method to reduce non-cephalic presentation at time of delivery. MethodsRetrospective audit of all the ECV procedures performed at a tertiary women’s hospital between Jan 2010 and Jan 2020. ResultsThe success rate of ECV was 54.5 %. The rate of vaginal birth following successful ECV was 73.6 % and rate of Caesarean 26.4 %, compared to 96.4 % for those with unsuccessful ECV (P < 0.0001). Factors found to be associated with increased success rates was the use of Intravenous terbutaline (P = 0.03), fetal birth weight ≥3.5 kg (P = 0.0001) and when the procedure is performed by an experienced operator who performed over 20 ECV procedures (P < 0.0001). ConclusionECV is a safe and effective procedure to reduce Caesarean section rates secondary to breech presentation. A dedicated ECV clinic with experienced operators and the use of intravenous terbutaline could improve success rate of ECV and reduce the number of Caesareans for breech presentation.

Practical utilization of cardiac computed tomography for the success in complex coronary intervention.

Percutaneous coronary intervention (PCI) for complex lesions is still technically demanding and is associated with less favorable procedural parameters such as lower success rate, longer procedural time, higher contrast volume and unexpected complications. Because the conventional angiographic analysis is limited by the inability to visualize the plaque information and the occluded segment, cardiac computed tomography has evolved as an adjunct to invasive angiography to better characterize coronary lesions to improve success rates of PCI. Adding to routine image reconstructions by coronary computed tomography angiography, the thin-slab maximum intensity projection method, which is a handy reconstruction technique on an ordinary workstation, could provide easy-to-understand images to reveal the anatomical characteristics and the lumen and plaque information simultaneously, and then assist to build an in-depth strategy for PCI. Especially in the treatment of chronic total occlusion lesion, these informations have big advantages in the visualization of the morphologies of entry and exit, the occluded segment and the distribution of calcium compared to invasive coronary angiography. Despite of the additional radiation exposure, contrast use and cost for cardiac computed tomography, the precise analysis of lesion characteristics would consequently improve the procedural success and prevent the complication in complex PCI.

PowerSynth Design Automation Flow for Hierarchical and Heterogeneous 2.5-D Multichip Power Modules

As a critical energy-conversion system component, power semiconductor modules and their layout optimization has been identified as a crucial step in achieving the maximum performance and density for wide bandgap technologies (i.e., GaN and SiC). New packaging technologies are also introduced to produce reliable and efficient multichip power module (MCPM) designs to push the current limits. The complexity of the MCPM layout is surpassing the capability of a manual, iterative design process to produce an optimum design with agile development requirements. An electronic design automation tool called PowerSynth has been introduced with on-going research toward enhanced capabilities to speed up the optimized MCPM layout design process. As a part of this continuing research, in PowerSynth v1.9, a constraint-aware layout engine has been developed, which enables integrating heterogeneous components, handling complex geometry, exploring a larger solution space, improved success rate, and providing options for multiobjective optimization algorithms. The layout engine is generic, scalable, and efficient in performing electro-thermal optimizations on both 2-D and 2.5-D power modules. To validate these enhanced design capabilities, a 2.5-D full-bridge power module layout is designed, optimized, fabricated, and tested with measurement results matching closely with model prediction. This result closes the loop in the power electronics design process with an experimentally validated module design automation flow.

Position-related content acquisition for CCM

The Content-Centric Networking (CCN) depends on reverse paths and limited broadcast to achieve content acquisition, but the reverse-path disruption due to node mobility leads to content acquisition failures and flooding results in considerable content acquisition costs. In this paper, we propose a Unicast-based content acquisition scheme for Content-Centric MANET (UCCM) to reduce content acquisition costs and improve success rates. UCCM employs the address-centric unicast instead of the content-centric broadcast to achieve the content acquisition, so the content acquisition cost is lowered. Moreover, a requester acquires the content from the nearest provider in the address-centric unicast way, so the content is returned to a requester based on the requester's address rather than the reverse paths. UCCM is evaluated, and the analysis results show that UCCM reduces the content acquisition cost by nearly 63.8% and improve the success rate by nearly 5.9%.

Risk factors and management strategies associated with non-response to aminosalicylates as a maintenance treatment in ulcerative colitis.

Aminosalicylates (5-ASA) are used as the first-line maintenance treatment in patients with mild-moderate ulcerative colitis (UC). Early identification of patients at high risk for 5-ASA non-response and appropriate therapeutic escalation are essential to avoid disease progression. However, the absence of a standardized definition for treatment success makes this a challenging task. The focus of the current review was to describe the risk factors and management strategies associated with 5-ASA non-response. Rates of 5-ASA failure can vary from 17 % to 75 % according to different success definitions, of which clinical relapse is the most prevalent and studied condition. Younger age and endoscopic activity at diagnosis, extensive colitis, early need for corticosteroids, elevated inflammatory markers and non-adherence are consistent risk factors of 5-ASA failure. Given the effectiveness, safety profile and tolerability of this medication, therapy optimization is critical before treatment escalation. Combined use of systemic and topical therapy at an appropriate dose in a once-daily administration and control of adherence could improve success rates.

Synthesis, biological activities and docking studies of pleuromutilin derivatives with piperazinyl urea linkage

Antibiotics resistance is becoming increasingly common, involving almost all antibiotics on the market. Diseases caused by drug resistant bacteria, such as MRSA, have high mortality and negatively affect public health. The development of new drugs would be an effective means of solving this problem. Modifications based on bioactive natural products could greatly shorten drug development time and improve success rate. Pleuromutilin, a natural product from the basidiomycete bacterial species, is a promising antibiotic candidate. In this study, a series of novel pleuromutilin derivatives possessing piperazinyl urea linkage were efficiently synthesised, and their antibacterial activities and bactericidal properties were evaluated via MIC, MBC and Time-kill kinetics assays. The results showed that all compounds exhibited potent activities against tested strains, especially MRSA strains with MIC values as low as 0.125 μg/mL; 8 times lower than that of marketed antibiotic Tiamulin. Docking studies indicate substituted piperazinyl urea derivatives could provide hydrogen bonds and initiate π-π stacking between molecules and surrounding residues.

Flipped Classrooms for Introductory Computer Programming Courses

Teaching and learning how to program are not easy tasks. Disapproval and dropout rates are a concern for everyone concerned with the topic. Therefore, it is necessary to look for strategies that improve the motivation of students who start a programming course, also improving success rates and decreasing dropout rates. The inverted class model, or flipped classroom, has been used in several experiments, showing very good results. The objectives of this teaching-learning technique is to change the traditional order: students have contact with new subjects before the classroom, using videos, texts or other material, as well as small online tests to check their knowledge. In this way, the face-to-face classes are reserved for discussion, doubts and application of previously acquired knowledge. The purpose of this paper is to analyze the scientific production on Flipped classrooms in introductory programming courses indexed in Elsevier’s Scopus. The sample is composed by 45 articles in total. The results obtained by bibliometric analysis showed when and where those documents are published, who are the authors and what is the focus of said articles. We also analyzed the most cited documents. We made a summary of the articles, namely in what refers to the sample size of the experiences, which programming language is used, in which universities the articles are made, which technology is used, as well as which methods are used in order to create inverted classes and which are the objectives and results of these experiences reported on the articles.. We managed to get a global view of the theme, getting a strong analysis for those who want to use flipped classrooms for teaching programming.

Population Knowledge and Attitude Toward Emergency Management of Avulsed Permanent Teeth

Objective: To evaluate the knowledge of patients treated in a public University concerning dental avulsion and its emergency first-aid management. Material and Methods: Three hundred patients were invited to answer a questionnaire about demographic characteristics, attitude and knowledge of first-aid management of dental avulsion. Chi-square test was used to assess the association between knowledge about dental replantation and education level. Results: Female gender (66.7%) aged from 31 to 40 years (31.3%) with high school education (50.3%) predominated among all the participants. It was not found a difference between education level and management of avulsed permanent teeth (p=0.076), and 66% of the respondents were not able to do the replantation. In relation to the management of avulsed tooth, 42.7% of the respondents would brush the tooth and if the replantation was not possible, most of them would choose inappropriate media for storage. The association between the storage medium and educational level showed to be statistically significant (p=0.043). Conclusion: It was possible to notice the lack of knowledge about this subject, and it could result in the worst prognosis. In avulsion cases, the subsequent root resorptions may lead to the loss of the child's tooth. It is important to implement educational campaigns to spread knowledge and improve success rates of permanent avulsed teeth

Success Rates for the Objectives of US State Cancer Control Plans: A First Look.

BackgroundA well-designed cancer control plan is an important tool for a nation, state, or community to address the burden of cancer. Furthermore, it provides the opportunity to devise and implement measurable objectives. However, there has been little to no assessment of the success rates of such objectives.MethodsI compared the success rate of objectives between US states’ current plan and most recent past plan to determine the proportion of success in the United States overall. I also tested possible reasons for low success rates.ResultsThe mean success rate was 20% for stringent successes (only exact matches between plans) and 28% for loose successes (exact and similar matches between plans). The magnitude of change in percentage between the baseline and target for loose objectives significantly predicted success (P = .0347). Higher change resulted in lower success. However, neither the number of objectives nor the level of overlap significantly predicted success rate. Nor was population size, region, or rural–urban status significantly related to success rate. The most successful states had high proportions of objectives that were measurable and a high number of overlapping objectives.ConclusionI found that objective success rates were low for cancer control plans. To improve success rates, I suggest that future cancer control plans ensure each objective has a measurable baseline and realistically attainable target.

Pretreatment with Ranitidine Bismuth Citrate May Improve Success Rates of Helicobacter pylori Eradication: A Prospective, Randomized, Controlled and Open-Label Study.

Effective Helicobacter pylori (H. pylori) eradication is a major public health concern; however, eradication failure rates with the standard triple therapy remain high. We aimed to investigate the effectiveness and tolerability of ranitidine bismuth citrate (RBC) pretreatment before standard triple therapy for H. pylori eradication. A prospective, randomized, controlled, and open-label clinical trial was conducted from June to December 2019. H. pylori eradication rate, safety, and tolerability were compared between the standard treatment group (esomeprazole, amoxicillin, and clarithromycin for 7 days) and RBC pretreatment group (RBC for 2 weeks before standard triple therapy). This trial ended earlier than estimated owing to the N-nitrosodimethylamine concerns with ranitidine. Success rates of H. pylori eradication were 80.9% and 67.3% in the RBC pretreatment (n = 47) and standard treatment (n = 52) (p = 0.126) groups, respectively. Our trial was discontinued earlier than planned; however, a statistical significance would be achieved by expansion of our data (p = 0.031) if patient enrollment numbers reached those initially planned. Adverse event rates were comparable between groups (25.5% in the pretreatment group vs. 28.8% in the standard treatment group), without serious event. Tolerability was excellent in both groups, recorded as 97.9% and 100% in the pretreatment and standard treatment groups, respectively. Compared with the standard triple regimen, RBC pretreatment for 2 weeks may achieve higher H. pylori eradication rates, with excellent safety and tolerability. However, this study necessitates further validation as it was discontinued early owing to the N-nitrosodimethylamine issues of ranitidine.

Blind and lightwand guided tracheal intubation: Incidence of esophageal intubation

The ILMA is a modification of the laryngeal mask airway and performs as an effective supraglottic airway device. It is also designed to serve as a conduit for orotracheal intubation. Intubation through the ILMA is usually a blind procedure. However, blind intubation may at times be unsuccessful. Devices such as the fibreoptic bronchoscope and the lightwand have been shown to improve success rates of intubation through the ILMA. This randomized study was conducted on 60 adult patients with normal airways undergoing scheduled surgery under general anaesthesia. Patients in the blind group (n = 30) were intubated blindly through the ILMA and patients in the lightwand group (n = 30) were intubated via the ILMA using lightwand without the inner stylet. Five patients had modified Mallampati equivalent to class III, and they were evenly distributed between the two groups. Other airway parameters in these five patients were within normal limits and they were not anticipated to have difficult airways. No patient belonging to modified Mallampati class 1V was involved in the study.

Organizational Change Skills: An Empirical Cross-National Study

This research is premised on the proposition that mastering organizational change skills may help improve success rate of change initiatives. The overall purpose of this empirical, cross-national study was to explore whether perceptions of organizational change skills differ across nations. Using a convenience sample, structured interviews were conducted with 90 managers and executives in three regions: the USA, the Baltics and South America to collect quantitative and qualitative data. Statistical significance of between-group differences in means was obtained with the help of one-way ANOVA, and differences in percentages were established using a chi square test. Most of the change skills were perceived similarly across the three regions, but nevertheless, there were some differences. More communication and managing the change process skills were believed to be present in organizations in the USA, while understanding internal and external environment was more characteristic of the Baltics and South America. Respondents in these two regions also considered interpersonal and social skills to be more important. Respondents’ awareness of change skills was quite low without prompting. However, when prompted, all pre-established 11 groups of skills (Somerville & Whelan-Berry, 2009) were rated as important, and the majority of respondents were confident that these skills could be found in their organization. Given the relatively few differences that were found across the three regions, this suggests that cross-border dissemination of organizational change skills is possible, but each geography requires a slight adaptation. The findings also suggest that if those leading/managing change initiatives recognize that there are at least 11 groups of change skills, and cultivate these skills within the organization, this could increase the success rate of change initiatives. Given the paucity of empirical research relating to change skills generally, and cross-national considerations specifically, and the importance of change for organizations globally, this exploratory empirical research makes important contributions.

Use of Acetazolamide in the Postoperative Care of Endoscopic Cerebrospinal Fluid Leak Closure

Spontaneous cerebrospinal fluid (CSF) leaks are defined as leaks without identifiable etiology, often presenting as spontaneous rhinorrhea. This is thought to be a variant of idiopathic intracranial hypertension (IIH). Spontaneous CSF leak closure often requires surgery, which has proven to be less successful than their non-spontaneous counterparts. There is growing evidence that active intracranial pressure (ICP) management in the postoperative care can improve success rates. We aim to give an update about the current use of acetazolamide in the postoperative care of spontaneous CSF leak closure.

Self-examination low-cost full-field OCT (SELFF-OCT) for patients with various macular diseases

PurposeThe treatment guidelines for many macular diseases rely on frequent monitoring with optical coherence tomography (OCT). However, the burden of frequent disease control leads to low therapy adherence in real life. OCT home monitoring would address this issue but requires an inexpensive and self-operable device. With self-examination low-cost full-field OCT (SELFF-OCT), our group has introduced a novel technology that may fulfill both requirements. In this pilot study, we report the initial experiences with a clinical prototype.MethodsFifty-one patients with different macular diseases were recruited in a cross-sectional study. The most common diseases were age-related macular degeneration (AMD; 39/51), diabetic macular edema (DME; 6/51), and retinal vein occlusion (RVO; 3/51). Patients received a short training in device usage and then performed multiple self-scans with the SELFF-OCT device. For comparison, scans with a standard clinical spectral domain (SD-)OCT were taken.ResultsAfter a brief training, 77% of the patients were able to successfully acquire images that were clinically gradable. No significant influence on success could be found for age (p = 0.08) or BCVA (p = 0.97). Relevant disease biomarkers in the most common retinal diseases could be detected.ConclusionsSELFF-OCT was used successfully for retinal self-examination and in the future could be used for retinal home monitoring. Future improvements in technology are expected to improve success rates and image quality.Trial registrationThe Trial was registered in the German Trial Register under the number DRKS00013755 on 14.03.2018.

Workflow of Ultrasound-Guided Arterial Access

Arterial line cannulations frequently are performed in various clinical settings to facilitate hemodynamic monitoring and metabolic assessments. Palpation-guided technique generally is performed due to the superficial nature of the peripheral arteries; however, this approach may be challenging in patients with obesity, edema, and hypotension. Difficult line placements are a significant contributor of reduced operating room efficiency due to time delays seen in procedural workflow. Real-time ultrasound guidance is shown to improve success rates of arterial cannulation and reduction in multiple attempts, leading to time efficiency and less likelihood of arterial spasms or hematoma formation. In this report, the authors demonstrate the workflow of ultrasound-guided arterial line cannulation, outline the features of their institutional multi-modal training project for quality improvement, and evaluate the possible effect of the initiative on surgical delays seen with difficult line placements.

Testing the efficacy and comparability of ZooMS protocols on archaeological bone

Collagen peptide mass fingerprinting, best known as Zooarchaeology by Mass Spectrometry (or ZooMS) when applied to archaeology, has become invaluable for the taxonomic identification of archaeological collagenous materials, in particular fragmentary and modified bone remains. Prior to MALDI-based spectrometric analysis, collagen needs to be extracted from the bone's inorganic matrix, isolated and purified. Several protocols are currently employed for ZooMS analysis, however their efficacy and comparability has not been directly tested. Here, we use four different ZooMS protocols to analyze 400 bone samples from seven archaeological sites, dating to between ~500,000–2000 years ago. One of them, single-pot solid-phase-enhance sample preparation (SP3), is used for the first time as a ZooMS protocol. Our results indicate that the least-destructive ZooMS protocol which uses an ammonium bicarbonate buffer as a means of extracting collagen is most suitable for bones with good collagen preservation, whereas the acid-based methodologies can improve success rates for bones with low-to-medium collagen preservation. Since preservation of biomolecules in archaeological bones is highly variable due to age and environmental conditions, we use the percent nitrogen by weight (%N) value as an independent semi-quantitative proxy for assessing collagen content and for predicting which bones will likely result in a successful ZooMS-based identification. We find that 0.26%N as a threshold for screening material could optimize the number of spectra which produce identifications using ZooMS. Significance statementWe present a direct comparison of three previously published ZooMS protocols for the analyses of archaeological bones, and the first use of an SP3-based approach to ZooMS analysis. Our results show that the acid-based ZooMS protocols increase the success rate for bones with low-medium collagen preservation. We identify 0.26%N as a threshold for optimizing the number of samples with enough collagen for successful peptide mass fingerprinting.

Genotypic Variability in Soybean [Glycine max (L.) Merrill] through Agrobacterium-Mediated Transformation

Embryonic tip explants of 92 Indian soyabean and 7 advanced breeding lines derived from soaked mature seeds were inoculated and co-cultivated for 5-day with Agrobacterium strain EHA105 carrying the binary vector pCambia1305.1 containing a hygromycin and kanamycin resistance gene as plant and bacterial selectable markers, respectively. Transient expression of transgene was monitored by histochemical localization of β-glucouronidase (GUSPlus) reporter activity in transformed ET tissues. A high genetic variability for Agrobacterium-infection ranging from 3.8 to 100% was observed in the form of transient GUS expression. Five highly efficient genotypes, namely DS-228, JS 335, JS 72-44, KHSb2, and JS 72-280 with transient GUS expression of 100, 98.1, 96.5, 96 and 92%, respectively were identified. In addition, various infectivity patterns in these genotypes were observed. Genotypes with very high transient GUS expression identified in this study may improve success rate of development of transgenic soybean.&#x0D; Plant Tissue Cult. &amp; Biotech. 30(2): 231-242, 2020 (December)

Point-of-Care Ultrasound for the Evaluation and Management of Febrile Infants.

Febrile infants frequently present to the emergency department (ED) and account for a vulnerable population at significant risk for serious bacterial infection. Appropriate evaluation and management are key to favorable outcomes but can present challenges for providers, especially in EDs where ill children are infrequently seen and pediatric-trained staff may not be available. Point-of-care ultrasound (POCUS) is integrated into the care of adults in the ED but is less commonly used for infants. We present a review of the current literature and proposed approach to using POCUS for bladder catheterization, lumbar puncture (LP), and vascular access in the resuscitation and evaluation of febrile infants. Point-of-care ultrasound can be a useful adjunct in the evaluation of febrile infants by facilitating higher success rates of infant bladder catheterization, LP, and intraosseous and intravenous (IV) line placement. Ultrasound has been shown to be a reliable method of evaluating bladder volumes before the catheterization of infants, reducing the number of attempts needed to obtain an adequate urine sample for testing and culture. Point-of-care ultrasound has also been shown to improve the yield of LPs in infants. Ultrasound is a rapid and accurate way of identifying the appropriate location and depth of needle insertion. Point-of-care ultrasound has also been shown to facilitate obtaining IV access in infants as well as confirming the proper placement of intraosseous lines. A growing body of evidence suggests that POCUS is a useful adjunct in the initial evaluation and resuscitation of febrile infants. It is the position of both the American Academy or Pediatrics, American College of Emergency Physicians, and the authors of this article that emergency physicians should be familiar with the indications and applications of POCUS in children. This technology should be used as an adjunct to improve success rates when performing bladder catheterization, LP, and obtaining intravenous/intraosseous access for infants.

Learning experience on sentinel cases of COVID-19 at a public healthcare institution: sharing on operating room processes.

Learning experience on sentinel cases of COVID-19 at a public healthcare institution: sharing on operating room processes.