The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials

Dronabinol, a natural cannabinoid, and its semi-synthetic derivative, nabilone, are marketed as medicines in several countries. The aim of our work was to systematically evaluate the frequency of adverse events related to dronabinol or nabilone treatment compared to placebo. Scientific databases were searched for placebo-controlled clinical studies of patients receiving either dronabinol or nabilone therapy with placebo control groups. This meta-analysis was reported following the PRISMA guidelines using the PICO format, and it was registered with the PROSPERO register. There were 16 trials included in the meta-analysis. In the nabilone studies, drowsiness was more than 7 times as frequent in patients treated with nabilone than in the placebo group (OR: 7.25; 95% CI: 1.64–31.95), and the risk of dizziness (OR: 21.14; 95% CI: 2.92–152.75) and dry mouth was also higher (OR: 17.23; 95% CI: 4.33–68.55). The frequency of headache was not different in the two groups. In case of dronabinol, the frequency of dry mouth (OR: 5.58; 95% CI: 3.19–9.78), dizziness (OR: 4.60 95% CI: 2.39–8.83) and headache (OR: 2.90; 95% CI: 1.07–7.85) was significantly higher in the dronabinol groups, whereas in case of nausea, drowsiness and fatigue there was no difference. The severity of adverse events was typically mild-to-moderate and transient. In a risk-benefit assessment, these adverse effects are acceptable compared to the achievable benefit. However, considering the diversity of the adverse effects, more studies are needed to provide a more accurate assessment on the side effect profiles of these two compounds.

Experimental Methods of Investigating Airborne Indoor Virus-Transmissions Adapted to Several Ventilation Measures

This study introduces a principle, which unifies two experimental methods for airborne indoor virus-transmissions adapted to several ventilation measures. A first-time comparison of mechanical/natural ventilation and air purifiers with regard to infection risks is achieved. Effortful computational fluid dynamics demand detailed boundary conditions for accurate calculations of indoor airflows, which are often unknown. Hence a suitable, simple and generalized experimental set up for identifying the spatial and temporal infection risk for different ventilation measures is required. A trace gas method is suitable for mechanical and natural ventilation with outdoor air exchange. For an accurate assessment of air purifiers based on filtration a surrogate particle method is appropriate. The release of a controlled rate of either trace gas or particles simulates an infectious person releasing virus material. Surrounding substance concentration measurements identify the neighborhood exposure. One key aspect of the study is to prove that the requirement of concordant results of both methods is fulfilled. This is the only way to ensure that the comparison of different ventilation measures described above is reliable. Two examples (a two person office, several classrooms) show how practical both methods are and how the principle is applicable for different types and sizes of rooms.

Evolution of Surgical Treatment of Metastatic Spine Tumors.

Purpose The treatment of cancer has transformed over the past forty years, with medical oncologists, radiation oncologists and surgeons working together to prolong survival times and minimize treatment related morbidity. With each advancement, the risk-benefit scale has been calibrated to provide an accurate assessment of surgical hazard. The goal of this review is to look back at how the role of surgery has evolved with each new medical advance, and to explore the role of surgeons in the future of cancer care. Methods A literature review was conducted, highlighting the key papers guiding surgical management of spinal metastatic lesions. Conclusion The roles of surgery, medical therapy and radiation have evolved over the past forty years, with new advances requiring complex multidisciplinary care.

Step-by-Step Model with Latent Parameters for Student Assessments

The article discusses the disadvantages of traditional approaches to statistical processing of assessments of intermediate attestations of students. We proposed a model in which the obtaining of the k grade on an ordinal scale is associated with the successful completion of k certification steps. By analogy with Item Response Theory used for processing test results the probability of a successful step is determined by latent parameters — the student's ability and the difficulty of the step. Methods for determining latent parameters from the estimates obtained and statistical procedures for checking the adequacy of the model are proposed. The data of processing the array of estimates are presented. The processing results confirmed the possibility of using the proposed mo­del for a more accurate assessment of students' ability and the difficulty of attestations.

Population Optimally Immunized after Accounting for Type-Specific COVID-19 Vaccine Waning Intervals: State-Level Prevalence and Trends

BACKGROUND: COVID-19 vaccines exhibit real-world waning effectiveness against SARS-CoV-2 infection within the first 3-6 months after a completed series. Consequently, the main metric tracked by the CDC (percent "fully vaccinated," with no adjustment for booster status) has become insufficiently informative. METHODS: We analyzed CDC daily vaccination data to quantify COVID-19 immunization status for 4 mutually-exclusive groups: (1) not immunized; (2) partially immunized (people who received the 1st dose of a 2-dose series); (3) immunized with waning immunity (previously immunized people whose booster dose is overdue); and (4) optimally immunized (people who: (a) received the Janssen vaccine <2 months ago or completed an mRNA vaccine series <6 months ago, or (b) received the Janssen vaccine >2 months ago or completed an mRNA vaccine series >6 months ago and received a booster dose.) RESULTS: The proportion of the total US population who were optimally immunized against COVID-19 fell from a high of 45.3% on July 17 to 29.4% on November 30. During November, the majority of states experienced a worsening trend in the percent of the total population who were overdue for a booster dose, including the 4 largest states, with percentage point increases of 3.5 in New York, 3.4 in California, 2.3 in Texas and 1.7 in Florida. CONCLUSIONS: Our proposed classification scheme accounts for type-specific vaccine waning intervals, provides an accurate assessment of progress toward national immunization goals, and reveals the urgent need for additional public health mitigation strategies to successfully combat the COVID-19 pandemic in the United States.

In-Line Inspection of Offshore Non-Piggable and Challenging 30" Subsea Flare Line

The objective of the paper is to present the success story of carrying out an in-line inspection (ILI) on a 50 years old offshore subsea flare line. The project was particularly challenging because the 30" flare line had no pigging facilities, a reducer, a subsea tie-in connection, as well as other restrictions. The paper shall outline the approach and methodology adopted to conduct the inspection in a safe and successful manner while adhering to the company and government health, safety, and environmental regulations and meeting the shutdown window. The 1 km long 30" flare line runs from a collector-separator platform to a flare tower. A site survey was conducted to identify process, space, and rigging related requirements. The shutdown window was allotted and fixed by the production teams. The line was first flushed to remove the hydrocarbons using a pumping spread mounted on a support vessel. This was followed by various modification works in addition to rigging up the temporary pigging traps. The works enlisted the help of support vessels and scaffolding teams. Extra controls were implemented due to the low maximum allowable operating pressure and the dirty pigging water in order to safeguard the property and environment. Eventually, 22 cleaning pigs were launched a in a train fashion. An Ultrasonic (UT) ILI tool was then used to gather information on the pipeline. Finally, the pipeline was dried using foam pigs. The operation was a success mainly because of the planning factor. Many activities were integrated including the availability of a maintenance barge which played a huge role in the operation. This was the first pigging operation on the flare line which was commissioned in 1971 - a total of 185 kg of debris was collected. Moreover, the UT inspection provided quantitative data which enabled an accurate assessment of the subsea pipeline integrity status. It is estimated that USD 4 million were saved by completing the works mainly through efficient planning and utilization of in-house available resources. The inspection results will form a cornerstone in development of future asset replacement plans for this category of flare lines. The success has created potential savings for another 21 challenging flare lines planned to be inspected for the next 5 years. The approach highlights the steps taken to conduct the quantitative ILI of an aged flare line (50 years old), with various inherent challenges, to explore the possibility of accurately inspecting and extending the remnant life of aged assets that are un-piggable, in a safe and environmentally friendly manner. Thus, resulting in positive impacts in savings and further optimizations in the asset replacement plans

The Use of Transformer Model in Opinion Summarisation

We live in an age of information, therefore collected data and documentation are practically treasure resources. All about a business and its development can be estimated with clarity via statistics. Any machine that could really analyse information to predict a projected outcome is known for being extremely vital for the business. It is critical for the system to provide accurate and useful knowledge of the products in order to conduct accurate assessment. Summarisation is a technique for obtaining a rundown from series of sentences in a study or observation that facilitates us with understanding the basic content of the knowledge expressed within. Simple and brief summaries of just a product will assist the system in performing prospective product research and development. In our paper, we use a deep learning framework that provides to extract clean, relevant, brief summaries from comprehensive customer feedback. Strategies of abstractive text summarisation is used. The method of extracting the primary keyword from a statement and using them in the summary is defined as extractive text summarisation. We utilise abstractive summarisation in this case, which evolves from sample information and provides the best feasible description. Utilising Transformer with Depth Scaling MultiHeaded Attention as well as GloVe word embedding with positional encoding, we illustrate an abstractive approach to extract summaries from the Amazon fine food reviews dataset. Transformer aids in the parallelisation of workloads in order to process data more quickly. We have used an Attention layer which boost the model's quality and enables it to become more effective. The BLUE rating is used to quantify the model's potency.

Quantitative analysis of submucosal excision depth in endoscopic resection for early Barrett’s cancer

Background Following endoscopic resection of early-stage Barrett’s esophageal adenocarcinoma (BEA), further oncologic management then fundamentally relies upon the accurate assessment of histopathologic risk criteria, which requires there to be sufficient amounts of submucosal tissue in the resection specimens. Methods In 1685 digitized tissue sections from endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) performed for 76 early BEA cases from three experienced centers, the submucosal thickness was determined, using software developed in-house. Neoplastic lesions were manually annotated. Results No submucosa was seen in about a third of the entire resection area (mean 33.8 % [SD 17.2 %]), as well as underneath cancers (33.3 % [28.3 %]), with similar results for both resection methods and with respect to submucosal thickness. ESD results showed a greater variability between centers than EMR. In T1b cancers, a higher rate of submucosal defects tended to correlate with R1 resections. Conclusion The absence of submucosa underneath about one third of the tissue of endoscopically resected BEAs should be improved. Results were more center-dependent for ESD than for EMR. Submucosal defects can potentially serve as a parameter for standardized reports.

Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy

Background: Despite recent advances in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC), overall survival remains poor with a 5-year cumulative survival of approximately 10%. Neoadjuvant (chemo- and/or radio-) therapy is increasingly incorporated in treatment strategies for patients with (borderline) resectable and locally advanced disease. Neoadjuvant therapy aims to improve radical resection rates by reducing tumor mass and (partial) encasement of important vascular structures, as well as eradicating occult micrometastases. Results from recent multicenter clinical trials evaluating this approach demonstrate prolonged survival and increased complete surgical resection rates (R0). Currently, tumor response to neoadjuvant therapy is monitored using computed tomography (CT) following the RECIST 1.1 criteria. Accurate assessment of neoadjuvant treatment response and tumor resectability is considered a major challenge, as current conventional imaging modalities provide limited accuracy and specificity for discrimination between necrosis, fibrosis, and remaining vital tumor tissue. As a consequence, resections with tumor-positive margins and subsequent early locoregional tumor recurrences are observed in a substantial number of patients following surgical resection with curative intent. Of these patients, up to 80% are diagnosed with recurrent disease after a median disease-free interval of merely 8 months. These numbers underline the urgent need to improve imaging modalities for more accurate assessment of therapy response and subsequent re-staging of disease, thereby aiming to optimize individual patient’s treatment strategy. In cases of curative intent resection, additional intra-operative real-time guidance could aid surgeons during complex procedures and potentially reduce the rate of incomplete resections and early (locoregional) tumor recurrences. In recent years intraoperative imaging in cancer has made a shift towards tumor-specific molecular targeting. Several important molecular targets have been identified that show overexpression in PDAC, for example: CA19.9, CEA, EGFR, VEGFR/VEGF-A, uPA/uPAR, and various integrins. Tumor-targeted PET/CT combined with intraoperative fluorescence imaging, could provide valuable information for tumor detection and staging, therapy response evaluation with re-staging of disease and intraoperative guidance during surgical resection of PDAC. Methods: A literature search in the PubMed database and (inter)national trial registers was conducted, focusing on studies published over the last 15 years. Data and information of eligible articles regarding PET/CT as well as fluorescence imaging in PDAC were reviewed. Areas covered: This review covers the current strategies, obstacles, challenges, and developments in targeted tumor imaging, focusing on the feasibility and value of PET/CT and fluorescence imaging for integration in the work-up and treatment of PDAC. An overview is given of identified targets and their characteristics, as well as the available literature of conducted and ongoing clinical and preclinical trials evaluating PDAC-targeted nuclear and fluorescent tracers.