Adaptive fuzzy control design for nonlinear systems with actuation and state constraints: An approach with no feasibility condition.

In this article, an adaptive fuzzy tracking control scheme is developed for a class of pure-feedback uncertain nonlinear systems in the presence of time-varying full-state constraints (TFSCs), actuators' nonlinearities and external disturbances. Fuzzy logic systems (FLSs) are employed as universal approximators to online estimate unknown nonlinear functions A barrier Lyapunov function (BLF) is used to deal with the state constraint problem. In contrast to numerous adjacent studies, this research diligently tackles the open problem relating to the virtual control laws (VCLs) feasibility in the BLF-based backstepping control design. The resolution to this problem involves formulating VCLs with predefined bounds. The utilization of disturbance observers within a backstepping framework allows for effective compensation of estimation errors arising from the implementation of a predefined bounded VCL. This approach also helps prevent the occurrence of the "complexity explosion", making it a practical solution. The control strategy being proposed guarantees that the output tracking error will effectively approach a small region near the origin. Additionally, all signals of the closed-loop system will remain uniformly ultimately bounded (UUB), and there will be adherence to all state-constraints, ensuring no violations occur. Ultimately, an illustrative simulation example is provided to demonstrate the efficacy of the theoretical findings.

Addressing the unmet clinical need for low-volume assays in early diagnosis of pancreatic cancer.

The incidental detection of pancreatic cysts, an opportunity for the early detection of pancreatic cancer, is increasing, owing to an aging population and improvements in imaging technology. The classification of pancreatic cystic precursors currently relies on imaging and cyst fluid evaluations, including cytology and protein and genomic analyses. However, there are persistent limitations that obstruct the accuracy and quality of information for clinicians, including the limited volume of the complex, often acellular, and proteinaceous milieu that comprises pancreatic cyst fluid. The constraints of currently available clinical assays lead clinicians to the subjective and inconsistent application of diagnostic tools, which can contribute to unnecessary surgery and missed pancreatic cancers. Herein, we describe the pathway toward pancreatic cyst classification and diagnosis, the volume requirements for several clinically available diagnostic tools, and some analytical and diagnostic limitations for each assay. We then discuss current and future work on novel markers and methods, and how to expand the utility of clinical pancreatic cyst fluid samples. Results of ongoing studies applying SERS as a detection mode suggest that 50 µL of pancreatic cyst fluid is more than sufficient to accurately rule out non-mucinous pancreatic cysts with no malignant potential from further evaluation. This process is expected to leave sufficient fluid to analyze a follow-up, rule-in panel of markers currently in development that can stratify grades of dysplasia in mucinous pancreatic cysts and improve clinical decision-making.

Favipiravir Efficacy And Safety For The Treatment Of Severe Coronavirus Disease 2019: A Retrospective Study.

BACKGROUND: Corona virus disease is caused by the enveloped, single stranded RNA virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becoming the deadliest disease of the century. Its global outbreak has led researchers to develop drugs or vaccines to prevent the spread of the disease. Favipiravir is an approved orally administered antiviral drug that selectively inhibits RNA-dependent RNA polymerase, used off-label to treat COVID-19. Objectives: The purpose of this study was to assess the efficacy and safety of this drug for severe COVID-19 infection. METHODS: This was an observational retrospective study, carried out at the ICU of King Saud Medical City (KSMC) from June 2020 to August 2020. Including a total of one thousand six hundred and ninety-nine patients (n=1699). Categorized into a treatment group (193 patients) who received Favipiravir along with standard care, and non-treatment group (1506 patients) who received standard care only. RESULTS: ICU all-cause mortality was similar in both groups i.e., (Treated group 38.3% Vs Untreated group 39.4%, 95% CI of difference: -6.6% to +8.4%; p = 0.8). The subgroup analysis of survivors as compared to deceased in the treatment group showed that survivors had significantly lower age, international normalising ratio (INR), blood urea nitrogen (BUN), and creatinine. The mean ICU length of stay (LOS) was shorter for survivors compared to deceased (11.2± 8.03 Vs 16.7±9.8 days respectively), while hospital LOS was almost similar between the two groups. Advanced age (OR 1.03 [95% CI: 1.01-1.06]; p=0.004), higher INR and BUN were significantly associated with increased odds of mortality. Comparison of lab investigations at day 1 and day 10 in the treatment group (regardless of outcome) showed that there was a significant increase in Alanine transaminase (ALT), alkaline phosphatase (ALK), and Bilirubin, while an insignificant trend of increase in Aspartate transaminase (AST) and creatinine was recorded. CONCLUSIONS: In this study, Favipiravir showed better therapeutic responses in patients with severe COVID-19 infection, in terms of average duration of stay in the intensive care unit and was well tolerated in the younger age, but showed no mortality benefit. However, elevated levels of inflammatory markers, including increased ALT, AST, BUN, bilirubin, and creatinine, needs to be carefully examined.

ASGE guideline on the role of endoscopy in the management of malignant hilar obstruction

This clinical guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for the management of patients with malignant hilar obstruction (MHO). This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework and addresses primary drainage modality (percutaneous transhepatic biliary drainage [PTBD] vs endoscopic biliary drainage [EBD]), drainage strategy (unilateral vs bilateral), and stent selection (plastic stent [PS] vs self-expandable metal stent [SEMS]). Regarding drainage modality, in patients with MHO undergoing drainage before potential resection or transplantation, the panel suggests against routine use of PTBD as first-line therapy compared with EBD. In patients with unresectable MHO undergoing palliative drainage, the panel suggests PTBD or EBD. The final decision should be based on patient preferences, disease characteristics, and local expertise. Regarding drainage strategy, in patients with unresectable MHO undergoing palliative stent placement, the panel suggests placement of bilateral stents compared with a unilateral stent in the absence of liver atrophy. Finally, regarding type of stent, in patients with unresectable MHO undergoing palliative stent placement, the panel suggests placing SEMSs or PSs. However, in patients who have a short life expectancy and who place high value on avoiding repeated interventions, the panel suggests using SEMSs compared with PSs. If optimal drainage strategy has not been established, the panel suggests placing PSs. This document clearly outlines the process, analyses, and decision processes used to reach the final recommendations and represents the official ASGE recommendations on the above topics.

ASGE guideline on the management of cholangitis

Cholangitis is a GI emergency requiring prompt recognition and treatment. The purpose of this document from the American Society for Gastrointestinal Endoscopy's (ASGE) Standards of Practice Committee is to provide an evidence-based approach for management of cholangitis. This document addresses the modality of drainage (endoscopic vs percutaneous), timing of intervention (<48 hours vs >48 hours), and extent of initial intervention (comprehensive therapy vs decompression alone). Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to formulate recommendations on these topics. The ASGE suggests endoscopic rather than percutaneous drainage and biliary decompression within 48 hours. Additionally, the panel suggests that sphincterotomy and stone removal be combined with drainage rather than decompression alone, unless patients are too unstable to tolerate more extensive endoscopic treatment.

ASGE guideline on the management of cholangitis.

Cholangitis is a GI emergency requiring prompt recognition and treatment. The purpose of this document from the American Society for Gastrointestinal Endoscopy's (ASGE) Standards of Practice Committee is to provide an evidence-based approach for management of cholangitis. This document addresses the modality of drainage (endoscopic vs percutaneous), timing of intervention (<48 hours vs >48 hours), and extent of initial intervention (comprehensive therapy vs decompression alone). Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to formulate recommendations on these topics. The ASGE suggests endoscopic rather than percutaneous drainage and biliary decompression within 48 hours. Additionally, the panel suggests that sphincterotomy and stone removal be combined with drainage rather than decompression alone, unless patients are too unstable to tolerate more extensive endoscopic treatment.

ASGE guideline on the role of endoscopy in the management of malignant hilar obstruction.

This clinical guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for the management of patients with malignant hilar obstruction (MHO). This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework and addresses primary drainage modality (percutaneous transhepatic biliary drainage [PTBD] vs endoscopic biliary drainage [EBD]), drainage strategy (unilateral vs bilateral), and stent selection (plastic stent [PS] vs self-expandable metal stent [SEMS]). Regarding drainage modality, in patients with MHO undergoing drainage before potential resection or transplantation, the panel suggests against routine use of PTBD as first-line therapy compared with EBD. In patients with unresectable MHO undergoing palliative drainage, the panel suggests PTBD or EBD. The final decision should be based on patient preferences, disease characteristics, and local expertise. Regarding drainage strategy, in patients with unresectable MHO undergoing palliative stent placement, the panel suggests placement of bilateral stents compared with a unilateral stent in the absence of liver atrophy. Finally, regarding type of stent, in patients with unresectable MHO undergoing palliative stent placement, the panel suggests placing SEMSs or PSs. However, in patients who have a short life expectancy and who place high value on avoiding repeated interventions, the panel suggests using SEMSs compared with PSs. If optimal drainage strategy has not been established, the panel suggests placing PSs. This document clearly outlines the process, analyses, and decision processes used to reach the final recommendations and represents the official ASGE recommendations on the above topics.

ASGE guideline on the role of endoscopy in the management of benign and malignant gastroduodenal obstruction.

This American Society for Gastrointestinal Endoscopy guideline provides evidence-based recommendations for the endoscopic management of gastric outlet obstruction (GOO). We applied the Grading of Recommendations, Assessment, Development and Evaluation methodology to address key clinical questions. These include the comparison of (1) surgical gastrojejunostomy to the placement of self-expandable metallic stents (SEMS) for malignant GOO, (2) covered versus uncovered SEMS for malignant GOO, and (3) endoscopic and surgical interventions for the management of benign GOO. Recommendations provided in this document were founded on the certainty of the evidence, balance of benefits and harms, considerations of patient and caregiver preferences, resource utilization, and cost-effectiveness.

Are morbidity and mortality case review practices in Scottish intensive care units aligned to national standards?

INTRODUCTION: Both Scottish and UK standards guidelines recommend that intensive care units should hold regular, structured, multidisciplinary morbidity and mortality meetings. The aim of this survey was to ascertain the nature of current practice with regards to morbidity and mortality case reviews and meetings in all intensive care units in Scotland. METHODS: Semi-structured telephone interviews were conducted with a consultant from all Scottish intensive care units. A list of intensive care units in Scotland was obtained from the Scottish Intensive Care Society Audit Group annual report. RESULTS: All 24 intensive care units (100%) in Scotland were surveyed. The interviews took an average of 20 min. The three cardiac intensive care units were excluded from analysis. All other intensive care units had morbidity and mortality meetings and 18 units had a morbidity and mortality clinical lead. Nineteen intensive care units held joint morbidity and mortality meetings, eight of which were regular. In all intensive care units, meetings were attended by consultants and trainees. In 14 intensive care units, meetings were attended by nurses, seven by allied health professionals, 1 by a manager and 11 by other professionals. All mortality cases in intensive care unit were discussed in 19 intensive care units, in the other two intensive care units, 10-20% of mortality cases were discussed. CONCLUSION: There is a wide variation in the processes of reviewing mortality cases and significant events in intensive care units across Scotland, and in the way morbidity and mortality meetings are organised and held. Based on this survey, there is scope for improving the consistency of approach to morbidity and mortality case reviews and meetings in order to improve education and facilitate shared learning.

Endoscopic ultrasound-guided liver biopsy: a multicenter experience.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided (EUS) liver biopsy (LB) is proposed as a newer method that offers several advantages over existing techniques for sampling liver tissue. This study evaluated the diagnostic yield of EUS-LB as the primary outcome measure. In addition, the safety of the technique in a large patient cohort was assessed. PATIENTS AND METHODS: Patients undergoing EUS for evaluation of elevated liver enzymes or hepatic disease were included in this prospective, non-randomized, multicenter study. EUS-LB was performed with EUS-fine needle aspiration (FNA; 19-gauge needle). Tissue was formalin-fixed and stained with hematoxylin and eosin, and trichrome. Using a microscope micrometer, specimen length was measured and the number of complete portal triads (CPTs) were counted. The main outcome measure was to assess the diagnostic yield of EUS-LB, and to monitor for any procedure-related complications. RESULTS: Patients (110; median age, 53 years; 62 women) underwent EUS-LB at eight centers. The indication was abnormal liver enzymes in 96 patients. LB specimens sufficient for pathological diagnosis were obtained in 108 of 110 patients (98 %). The overall tissue yield from 110 patients was a median aggregate length of 38 mm (range, 0 - 203), with median of 14 CPTs (range, 0 - 68). There was no statistical difference in the yield between bilobar, left lobe only, or right lobe only biopsies. There was one complication (0.9 %) where self-limited bleeding occurred in a coagulopathic and thrombocytopenic patient. This complication was managed conservatively. CONCLUSIONS: EUS-guided LB was a safe technique that yields tissue adequate for diagnosis among 98 % of patients evaluated.

An efficient pancreatic cyst identification methodology using natural language processing.

Pancreatic cancer is one of the deadliest cancers, mostly diagnosed at late stages. Patients with pancreatic cysts are at higher risk of developing cancer and their surveillance can help to diagnose the disease in earlier stages. In this retrospective study we collected a corpus of 1064 records from 44 patients at Indiana University Hospital from 1990 to 2012. A Natural Language Processing (NLP) system was developed and used to identify patients with pancreatic cysts. NegEx algorithm was used initially to identify the negation status of concepts that resulted in precision and recall of 98.9% and 89% respectively. Stanford Dependency parser (SDP) was then used to improve the NegEx performance resulting in precision of 98.9% and recall of 95.7%. Features related to pancreatic cysts were also extracted from patient medical records using regex and NegEx algorithm with 98.5% precision and 97.43% recall. SDP improved the NegEx algorithm by increasing the recall to 98.12%.

Laparoscopic restoration of intestinal continuity (the LapRICon procedure): a safe and feasible technique for restoration of transanal defecation.

BACKGROUND: The restoration of intestinal continuity after open abdominal surgery can be technically challenging. The authors describe their experience with the laparoscopic approach to attempted reversal for patients with an exteriorized intestine. METHODS: A consecutive series of patients under the care of a single surgeon (D.B.) underwent laparoscopic restoration of intestinal continuity (LapRICon). All the patients first underwent exclusion of intraabdominal sepsis with computed tomography (CT) scanning and then preoperative localization of proximal and distal bowel ends via water-soluble contrast studies. Stomal sites were used for initial access, establishment of capnoperitoneum, and formation of anastomoses extracorporeally. All adhesiolysis and mobilization of bowel ends were performed intracorporeally. Pre-, intra-, and postoperative data were collected for all the patients. Return of intestinal function, overall hospital length of stay, and postoperative complications were collected. Nonparametric statistics were used to analyze the data. RESULTS: A total of 13 patients (6 women) were followed up for 9 months (interquartile range [IQR], 5-16 months). The median age of the patients was 39 years (IQR, 28-64 years). Nine patients were categorized as American Society of Anesthesiology (ASA) class 1. One patient was ASA 2, and the remaining patients were ASA 3. The median colorectal physiologic and operative severity scores for the enumeration of mortality and morbidity (CR-POSSUM) were 0.68 (IQR, 0.68-1.72). The intraoperative blood loss was minimal (median 30 ml; IQR, 20-125 ml). The median operative duration was 240 min (IQR, 180-240 min), and a median of 4 ports (IQR, 3-5 ports) were used. Enterocolonic anastomoses were fashioned in six patients, enterorectal anastomoses in two patients, and enteroentero anastomoses in three patients. A single patient had multiple anastomoses. The median time to return of intestinal function was 5 days (IQR, 3-13 days), and the overall hospital stay was 8 days (IQR, 5-24 days). Four complications (25%) (2 recurrent fistulas, 1 anastomotic leak, and 1 open conversion) occurred in this series of patients. CONCLUSIONS: The LapRICon procedure is a feasible technique with acceptable morbidity. Several principles and techniques are described to aid the surgeon who wishes to embark on use of such a technique.

Screening of Tanzanian medicinal plants against Plasmodium falciparum and human immunodeficiency virus.

Medicinal plants used to treat infectious diseases in Bunda district, Tanzania, were screened for activity against Plasmodium falciparum and Human Immunodeficiency Virus Type 1 (HIV-1, IIIB strain) and Type 2 (HIV-2, ROD strain). Antiplasmodial activity was observed for the 80 % MeOH extract of Ormocarpum kirkii (root; MIC = 31.25 microg/mL), Combretum adenogonium (leaves), Euphorbia tirucalli (root), Harrisonia abyssinica (root), Rhynchosia sublobata (root), Sesbania sesban (root), Tithonia diversifolia (leaves), and Vernonia cinerascens (leaves; MIC value of 62.5 microg/mL). With regard to HIV, 80 % MeOH extracts of Barleria eranthemoides (root), Combretum adenogonium (leaves and stem bark), Elaeodedron schlechteranum (stem bark and root bark), Lannea schweinfurthii (stem bark), Terminalia mollis (stem bark and root bark), Acacia tortilis (stem bark), Ficus cycamorus (stem bark) and Indigofera colutea (shoot), as well as H2O extracts from Barleria eranthemoides (root), Combretum adenogonium (leaves and stem bark), and Terminalia mollis (stem bark and root bark) exhibited IC50 values below 10 microg/mL against HIV-1 (IIIB strain). The highest anti-HIV-1 activity value was obtained for the B. eranthemoides 80 % MeOH root extract (IC50 value 2.1 microg/mL). Only a few extracts were active against HIV-2, such as the 80 % MeOH extract from Lannea schweinfurthii (stem bark) and Elaeodedron schlechteranum (root bark), showing IC50 values < 10 microg/mL.

Duplex ultrasound scanning (DUS) versus computed tomography angiography (CTA) in the follow-up after EVAR.

INTRODUCTION: Computed tomography angiography (CTA) is the gold standard follow-up modality after endovascular aneurysm repair (EVAR). A potential alternative noninvasive and less expensive modality is duplex ultrasound scanning (DUS). METHODS: We studied 314 follow-up paired scans (DUS and CTA) in 59 patients with EVAR. RESULTS: Endoleak--Endoleak was detected in 23.7% patients. The sensitivity and specificity rates of DUS were 54% and 95.3%, respectively. All 9 endoleaks that needed secondary intervention were detected on DUS. Eight of those were identified within a year after EVAR. Sac size--The mean difference in maximum diameter between the DUS and CTA was < or =5 mm in 84.5% of cases and < or =10 mm in 97.1%. Graft patency--There was 100% agreement between CTA and DUS. CONCLUSIONS: Duplex ultrasound scanning was reliable as it detected all the leaks that needed reintervention after EVAR. Duplex ultrasound scanning showed similar results to CTA in detecting sac size and patency.

Comparing methods for identifying pancreatic cancer patients using electronic data sources.

We sought to determine the accuracy of two electronic methods of identifying pancreatic cancer in a cohort of pancreatic cyst patients, and to examine the reasons for identification failure. We used the International Classification of Diseases, 9(th) Edition (ICD-9) codes and natural language processing (NLP) technology to identify pancreatic cancer in these patients. We compared both methods to a human-validated gold-standard surgical database. Both ICD-9 codes and NLP technology achieved high sensitivity for identifying pancreatic cancer, but the ICD-9 code method achieved markedly lower specificity and PPV compared to the NLP method. The NLP method required only slightly greater expenditures of time and effort compared to the ICD-9 code method. We identified several variables influencing the accuracy of ICD-9 codes to identify cancer patients including: the identification algorithm, kind of cancer to be identified, presence of other conditions similar to cancer, and presence of conditions that are precancerous.

Use of dextropropoxyphene + acetaminophen fixed-dose combination in psychiatric hospital in Bahrain: is there a cause for concern?

There are concerns about the safety of the dextropropoxyphene and acetaminophen fixed-dose combination, particularly in patients with psychiatric morbidity, which has led to a phased withdrawal of this fixed-dose combination in many countries. A retrospective prescription audit was conducted to evaluate the dextropropoxyphene + acetaminophen fixed-dose combination prescribing pattern in the major psychiatric hospital of Bahrain. The data analysis was performed using SPSS/PC+ version 14.0. Prescriptions with the dextropropoxyphene + acetaminophen fixed-dose combination comprised 11.8% of all dispensed prescriptions and in most instances for outpatients undergoing substance abuse rehabilitation. Nearly half of the patients received >or=20 tablets of this fixed-dose combination (mean +/- SD: 30.9 +/- 13.1; range 20-126) as multiple doses. The dextropropoxyphene + acetaminophen fixed-dose combination was often co-prescribed with psychotropics, such as benzodiazepines (BZDs) (25.4%), BZDs + antidepressants (62.9%), BZDs + antipsychotics (3.7%) and BZDs + anticonvulsants (1.9%). Approximately 40% of prescriptions with the dextropropoxyphene + acetaminophen fixed-dose combination were written 'as required' (prn), basis. Despite poor safety and efforts to restrict or withdraw worldwide, the dextropropoxyphene + acetaminophen fixed-dose combination continues to be irrationally prescribed to outpatients undergoing substance abuse rehabilitation in Bahrain. Health policy decision-makers should introduce a phased withdrawal of this drug from clinical use. In the meanwhile, it is important to create awareness among prescribers of the risks associated with over-dosage of the dextropropoxyphene + acetaminophen fixed-dose combination and its interaction with other psychotropic medications.

EUS-guided FNA diagnostic yield of malignancy in solid pancreatic masses: a benchmark for quality performance measurement.

BACKGROUND: The diagnostic yield of EUS-guided FNA (EUS-FNA) of solid pancreatic masses is a potential benchmark for EUS-FNA quality, because the majority of EUS-FNA of solid pancreatic masses should be diagnostic for malignancy. OBJECTIVES: To determine the cytologic diagnostic rate of malignancy in EUS-FNA of solid pancreatic masses and to determine if variability exists among endoscopists and centers. DESIGN: Multicenter retrospective study. PATIENTS: EUS centers provided cytology reports for all EUS-FNAs of solid, noncystic, >or=10-mm-diameter, solid pancreatic masses during a 1-year period. MAIN OUTCOME MEASUREMENT: Cytology diagnostic of pancreatic malignancy. RESULTS: A total of 1075 patients underwent EUS-FNA at 21 centers (81% academic) with 41 endoscopists. The median number of EUS-FNA of solid pancreatic masses performed during the year per center was 46 (range, 4-177) and per endoscopist was 19 (range, 1-97). The mean mass dimensions were 32 x 27 mm, with 73% located in the head. The mean number of passes was 3.5. Of the centers, 90% used immediate cytologic evaluation. The overall diagnostic rate of malignancy was 71%, 95% confidence interval 0.69%-0.74%, with 5% suspicious for malignancy, 6% atypical cells, and 18% negative for malignancy. The median diagnostic rate per center was 78% (range, 39%-93%; 1st quartile, 61%) and per endoscopist was 75% (range, 0%-100%; 1st quartile, 52%). LIMITATIONS: Retrospective study, participation bias, and varying chronic pancreatitis prevalence. CONCLUSIONS: (1) EUS-FNA cytology was diagnostic of malignancy in 71% of solid pancreatic masses and (2) endoscopists with a final cytologic diagnosis rate of malignancy for EUS-FNA of solid masses that was less than 52% were in the lowest quartile and should evaluate reasons for their low yield.