Use of a Novel Artificial Intelligence System Leads to the Detection of Significantly Higher Number of Adenomas During Screening and Surveillance Colonoscopy: Results From a Large, Prospective, US Multicenter, Randomized Clinical Trial.

INTRODUCTION: Adenoma per colonoscopy (APC) has recently been proposed as a quality measure for colonoscopy. We evaluated the impact of a novel artificial intelligence (AI) system, compared with standard high-definition colonoscopy, for APC measurement. METHODS: This was a US-based, multicenter, prospective randomized trial examining a novel AI detection system (EW10-EC02) that enables a real-time colorectal polyp detection enabled with the colonoscope (CAD-EYE). Eligible average-risk subjects (45 years or older) undergoing screening or surveillance colonoscopy were randomized to undergo either CAD-EYE-assisted colonoscopy (CAC) or conventional colonoscopy (CC). Modified intention-to-treat analysis was performed for all patients who completed colonoscopy with the primary outcome of APC. Secondary outcomes included positive predictive value (total number of adenomas divided by total polyps removed) and adenoma detection rate. RESULTS: In modified intention-to-treat analysis, of 1,031 subjects (age: 59.1 ± 9.8 years; 49.9% male), 510 underwent CAC vs 523 underwent CC with no significant differences in age, gender, ethnicity, or colonoscopy indication between the 2 groups. CAC led to a significantly higher APC compared with CC: 0.99 ± 1.6 vs 0.85 ± 1.5, P = 0.02, incidence rate ratio 1.17 (1.03-1.33, P = 0.02) with no significant difference in the withdrawal time: 11.28 ± 4.59 minutes vs 10.8 ± 4.81 minutes; P = 0.11 between the 2 groups. Difference in positive predictive value of a polyp being an adenoma among CAC and CC was less than 10% threshold established: 48.6% vs 54%, 95% CI -9.56% to -1.48%. There were no significant differences in adenoma detection rate (46.9% vs 42.8%), advanced adenoma (6.5% vs 6.3%), sessile serrated lesion detection rate (12.9% vs 10.1%), and polyp detection rate (63.9% vs 59.3%) between the 2 groups. There was a higher polyp per colonoscopy with CAC compared with CC: 1.68 ± 2.1 vs 1.33 ± 1.8 (incidence rate ratio 1.27; 1.15-1.4; P < 0.01). DISCUSSION: Use of a novel AI detection system showed to a significantly higher number of adenomas per colonoscopy compared with conventional high-definition colonoscopy without any increase in colonoscopy withdrawal time, thus supporting the use of AI-assisted colonoscopy to improve colonoscopy quality ( ClinicalTrials.gov NCT04979962).

Using behavioural science to explore impact and implementation of obstetric anaesthesia training in Tanzania, Nepal and Bangladesh: a qualitative evaluation study with obstetric anaesthesia providers.

Objective: High quality obstetric anaesthetic care is integral to reducing preventable maternal deaths in Low-and-Middle-Income-Countries (LMICs). We applied behavioural science to evaluate SAFE Obstetrics, a 3-day Continuing Professional Development (CPD) course, on physician and non-physician anaesthetists' practice behaviours across 3 LMICs.Methods: Seven anaesthetist Fellows from Bangladesh, Nepal and Tanzania were trained in qualitative methods and behavioural science. Structured interviews were undertaken by Fellows and two UK behavioural scientists with course participants. Interviews were based on the Theoretical Domains Framework: a comprehensive framework of influences on behaviour change. Interviews were recorded, transcribed and analysed using content and thematic analysis.Results: 78 physician and non-physician anaesthetists participated (n = 26 Bangladesh, n = 24 Nepal and n = 28 Tanzania). Participants reported positive improvements in patient-centered working, safety, teamwork and confidence. Across countries, we found similar barriers and facilitators: environmental resources, a strong professional identity and positive social influences were key facilitators of change.Conclusion: This multi-country theory-based evaluation highlighted the impact of SAFE Obstetrics on participants' clinical practice. A supportive work environment was crucial for implementing learning following training; CPD courses in LMICs must furnish participants with skills and equipment to address training implementation challenges. Building local behavioural science capacity can strengthen LMIC health intervention evaluations.

A Case-Based Approach to Constipation in Primary Care.

Primary care physicians frequently evaluate patients with constipation. The history is crucial in uncovering warning symptoms and signs that warrant colonoscopy. Particular elements in the history and rectal examination also can provide clues regarding the underlying etiology. Regardless of etiology, lifestyle modifications, fiber, and laxatives are first-line therapies. Patients who fail first-line therapies can be offered second-line treatments and/or referred for testing of defecatory function. In those with severely refractory symptoms, referrals to a gastroenterologist and a surgeon should be considered.

Gastric food retention at endoscopy is associated with severity of liver cirrhosis.

BACKGROUND: Gastrointestinal symptoms are prevalent in patients with cirrhosis. Cirrhotic patients have a known predilection to delayed gastric emptying compared to those without cirrhosis. However, the contributing factors have not been fully elucidated. Retained gastric food on esophagogastroduodenoscopy (EGD) has been used as a surrogate marker for delayed gastric emptying with reasonably high specificity. Therefore, we hypothesize that the frequency of retained gastric food contents at EGD will be higher in a cirrhotic population compared to a control population without liver disease. Additionally, we hypothesize that increased frequency of gastric food contents will be associated with increased severity of cirrhosis. AIM: To determine the relative frequency of delayed gastric emptying among cirrhotics as compared to non-cirrhotics and to identify associated factors. METHODS: We performed a retrospective case-control study of cirrhotic subjects who underwent EGD at an academic medical center between 2000 and 2015. Three hundred sixty-four patients with confirmed cirrhosis, who underwent a total of 1044 EGDs for the indication of esophageal variceal screening or surveillance, were identified. During the same period, 519 control patients without liver disease, who underwent a total of 881 EGDs for the indication of anemia, were identified. The presence of retained food on EGD was used as a surrogate for delayed gastric emptying. The relative frequency of delayed gastric emptying among cirrhotics was compared to non-cirrhotics. Characteristics of patients with and without retained food on EGD were compared using univariable and multivariable logistic regression analysis to identify associated factors. RESULTS: Overall, 40 (4.5%) patients had evidence of retained food on EGD. Cirrhotics were more likely to have retained food on EGD than non-cirrhotics (9.1% vs 1.4%, P < 0.001). Characteristics associated with retained food on univariable analysis included age less than 60 years (12.6% vs 5.2%, P = 0.015), opioid use (P = 0.004), Child-Pugh class C (24.1% Child-Pugh class C vs 6.4% Child-Pugh class A, P = 0.007), and lower platelet count (P = 0.027). On multivariate logistic regression analysis, in addition to the presence of cirrhosis (adjusted OR = 5.83; 95%CI: 2.32-14.7, P < 0.001), diabetes mellitus (types 1 and 2 combined) (OR = 2.34; 95%CI: 1.08-5.06, P = 0.031), opioid use (OR = 3.08; 95%CI: 1.29-7.34, P = 0.011), and Child-Pugh class C (OR = 4.29; 95%CI: 1.43-12.9, P = 0.01) were also associated with a higher likelihood of food retention on EGD. CONCLUSION: Cirrhotics have a higher frequency of retained food at EGD than non-cirrhotics. Decompensated cirrhosis, defined by Child-Pugh class C, is associated with a higher likelihood of delayed gastric emptying.

The rise of Clostridioides difficile infections and fall of associated mortality in hospitalized advanced cirrhotics.

BACKGROUND & AIMS: Cirrhotics are at increased risk of Clostridioides difficile infection (CDI) and its associated high morbidity and mortality. However, the impact of CDI in cirrhotics over time remains unclear. This study analyses prevalence and mortality in CDI in hospitalized patients with advanced cirrhosis over 15 years and identifies trends. METHODS: Using the Nationwide Inpatient Sample (NIS) from 1998 to 2014, 3 049 696 weighted patients with advanced cirrhosis (defined as evidence of decompensation or oesophageal varices) were identified using a validated algorithm of ICD-9-CM codes and included in the study. Trends were analysed using Cochran Armitage test and joinpoint regression and compared to the general population. Multivariable logistic regression was performed controlling for risk factors that affect mortality in cirrhotics. RESULTS: CDI prevalence in advanced cirrhotics increased from 0.8% to 2.6%, annual percent change (APC) 8.8% (compared to 7.6% for the general population), while CDI-related mortality decreased from 20.7% to 11.3%, APC -3.4% (compared to -2.0% for the general population), from 1998 to 2014. CDI independently increased mortality in advanced cirrhotics (OR 1.47, P < 0.001) and was associated with acute kidney injury (AKI) (OR 2.09, P < 0.001), which itself significantly increased mortality (OR 4.54, P < 0.001). Hepatic encephalopathy and Hispanic ethnicity were interestingly associated with a lower prevalence of CDI. CONCLUSIONS: CDI is increasingly common in advanced cirrhotics, but on the contrary, its associated mortality is decreasing. Despite improvements in outcomes in patients with advanced cirrhosis, CDI is associated with an increased mortality, driven by AKI, and therefore, requires aggressive identification and therapy.

Ultrasonographic Nonalcoholic Fatty Pancreas Is Associated with Advanced Fibrosis in NAFLD: A Retrospective Analysis.

BACKGROUND: Nonalcoholic fatty pancreas disease (NAF-P) is strongly linked with nonalcoholic fatty liver disease (NAFLD), but its relationship with advanced liver disease is unknown. AIMS: This study investigated the association between NAF-P and both advanced fibrosis and nonalcoholic steatohepatitis (NASH). METHODS: This retrospective study evaluated adults with biopsy-proven NAFLD with a sonogram within 1 year of liver biopsy. NAF-P was diagnosed by comparing the echogenicity of the pancreas to the kidney and was graded by severity. The primary outcome was the effect of NAF-P on the presence of advanced fibrosis and NASH, while secondary outcomes included the association of extensive NAF-P (grade II/III). Propensity score matching for independent risk factors of advanced fibrosis (age, gender, body mass index, and diabetes) was performed. RESULTS: One hundred and four patients were included in the study and 91 (87.5%) had NAF-P. After propensity score matching, NAF-P was significantly associated with advanced fibrosis (OR 10.52, p < 0.001) but not NASH (p = 0.27). Extensive NAF-P was predictive of advanced fibrosis (OR 3.35, p = 0.006) and NASH (OR 5.37, p < 0.001). NAF-P had a negative predictive value (NPV) of 93% for advanced fibrosis. When matching for the NAFLD fibrosis score in addition to the variables above, both NAF-P (OR 5.36, p = 0.001) and extensive NAF-P (OR 5.38, p = 0.002) still significantly predicted advanced fibrosis. CONCLUSION: NAF-P is predictive of advanced fibrosis, even when controlling for independent predictors of advanced fibrosis and the NAFLD fibrosis score. NAF-P has an excellent NPV and is a safe, inexpensive finding that can rule out advanced fibrosis.

Dopamine Transporter Dynamics of N-Substituted Benztropine Analogs with Atypical Behavioral Effects.

Atypical dopamine transporter (DAT) inhibitors, despite high DAT affinity, do not produce the psychomotor stimulant and abuse profile of standard DAT inhibitors such as cocaine. Proposed contributing features for those differences include off-target actions, slow onsets of action, and ligand bias regarding DAT conformation. Several 3α-(4',4''-difluoro-diphenylmethoxy)tropanes were examined, including those with the following substitutions: N-(indole-3''-ethyl)- (GA1-69), N-(R)-2''-amino-3''-methyl-n-butyl- (GA2-50), N-2''aminoethyl- (GA2-99), and N-(cyclopropylmethyl)- (JHW013). These compounds were previously reported to have rapid onset of behavioral effects and were presently evaluated pharmacologically alone or in combination with cocaine. DAT conformational mode was assessed by substituted-cysteine accessibility and molecular dynamics (MD) simulations. As determined by substituted-cysteine alkylation, all BZT analogs except GA2-99 showed bias for a cytoplasmic-facing DAT conformation, whereas cocaine stabilized the extracellular-facing conformation. MD simulations suggested that several analog-DAT complexes formed stable R85-D476 "outer gate" bonds that close the DAT to extracellular space. GA2-99 diverged from this pattern, yet had effects similar to those of other atypical DAT inhibitors. Apparent DAT association rates of the BZT analogs in vivo were slower than that for cocaine. None of the compounds was self-administered or stimulated locomotion, and each blocked those effects of cocaine. The present findings provide more detail on ligand-induced DAT conformations and indicate that aspects of DAT conformation other than "open" versus "closed" may facilitate predictions of the actions of DAT inhibitors and may promote rational design of potential treatments for psychomotor-stimulant abuse.

Nursing the critically ill surgical patient in Zambia.

Critical illness in the developing world is a substantial burden for individuals, families, communities and healthcare services. The management of these patients will depend on the resources available. Simple conditions such as a fractured leg or a strangulated hernia can have devastating effects on individuals, families and communities. The recent Lancet Commission on Global Surgery and the World Health Organization promise to strengthen emergency and essential care will increase the focus on surgical services within the developing world. This article provides an overview of nursing the critically ill surgical patient in Zambia, a lower middle income country (LMIC) in sub-Saharan Africa.

Avoidable perioperative mortality at the University Teaching Hospital, Lusaka, Zambia: a retrospective cohort study.

PURPOSE: Perioperative mortality has fallen in both high- and low-income countries over the last 50 years. An evaluation of avoidable perioperative mortality can provide valuable lessons to improve care; however, there is relatively little recent data from the Least Developed Countries in the world. We aimed to compare recent avoidable perioperative mortality in Lusaka, Zambia, with historical data from 1987. METHODS: We conducted a retrospective cohort study by identifying perioperative deaths within days of surgery and comparing the operating room and mortuary registers for the 2012 calendar year. Multiple independent raters from anesthesiology and surgery/obstetrics gynecology reviewed case notes, when available, to identify avoidable causes of death. RESULTS: Of the 18,010 surgical patients in 2012, 114 were identified as having died perioperatively within six days of surgery. Fifty-nine files were available for further analysis (52% of identified perioperative deaths). Eighteen (30%) of these cases were assessed as avoidable, 19 cases (32%) probably avoidable, 14 cases (24%) unavoidable, and eight cases (14%) unclear. Thirty-one (53%) cases had surgical factors contributing to death, 19 (32%) cases had anesthesia factors, and 18 (30%) cases had systems factors. Most of the avoidable deaths were attributed to multiple factors. Key factors leading to the avoidable deaths were delays in surgery, lack of the availability of blood, and poor postoperative care. CONCLUSIONS: Most deaths were avoidable, suggesting that patient outcomes in low-resource settings can be improved within current resources. The multifactorial nature of avoidability implies that an interprofessional approach is required to improve the quality of care.

Engineering oxidoreductases: maquette proteins designed from scratch.

The study of natural enzymes is complicated by the fact that only the most recent evolutionary progression can be observed. In particular, natural oxidoreductases stand out as profoundly complex proteins in which the molecular roots of function, structure and biological integration are collectively intertwined and individually obscured. In the present paper, we describe our experimental approach that removes many of these often bewildering complexities to identify in simple terms the necessary and sufficient requirements for oxidoreductase function. Ours is a synthetic biology approach that focuses on from-scratch construction of protein maquettes designed principally to promote or suppress biologically relevant oxidations and reductions. The approach avoids mimicry and divorces the commonly made and almost certainly false ascription of atomistically detailed functionally unique roles to a particular protein primary sequence, to gain a new freedom to explore protein-based enzyme function. Maquette design and construction methods make use of iterative steps, retraceable when necessary, to successfully develop a protein family of sturdy and versatile single-chain three- and four-α-helical structural platforms readily expressible in bacteria. Internally, they prove malleable enough to incorporate in prescribed positions most natural redox cofactors and many more simplified synthetic analogues. External polarity, charge-patterning and chemical linkers direct maquettes to functional assembly in membranes, on nanostructured titania, and to organize on selected planar surfaces and materials. These protein maquettes engage in light harvesting and energy transfer, in photochemical charge separation and electron transfer, in stable dioxygen binding and in simple oxidative chemistry that is the basis of multi-electron oxidative and reductive catalysis.