Clinical trial: Effects of pegozafermin on the liver and on metabolic comorbidities in subjects with biopsy-confirmed nonalcoholic steatohepatitis.

BACKGROUND: An approved therapy for nonalcoholic steatohepatitis (NASH) and fibrosis remains a major unmet medical need. AIM: To investigate the histological and metabolic benefits of pegozafermin, a glycoPEGylated FGF21 analogue, in subjects with biopsy-confirmed NASH. METHODS: This proof-of-concept, open-label, single-cohort study, part 2 of a phase 1b/2a clinical trial, was conducted at 16 centres in the United States. Adults (age 21-75 years) with NASH (stage 2 or 3 fibrosis, NAS≥4) and magnetic resonance imaging proton density fat fraction (MRI-PDFF) ≥8% received subcutaneous pegozafermin 27 mg once weekly for 20 weeks. Primary outcomes were improvements in liver histology, and safety and tolerability. RESULTS: Of 20 enrolled subjects, 19 completed the study. Twelve subjects (63%) met the primary endpoint of ≥2-point improvement in NAFLD activity score with ≥1-point improvement in ballooning or lobular inflammation and no worsening of fibrosis. Improvement of fibrosis without worsening of NASH was observed in 26% of subjects, and NASH resolution without worsening of fibrosis in 32%. Least-squares mean relative change from baseline in MRI-PDFF was -64.7% (95% CI: -71.7, -57.7; p < 0.0001). Significant improvements from baseline were also seen in serum aminotransferases, noninvasive fibrosis tests, serum lipids, glycaemic control and body weight. Adverse events (AEs) were reported in 18 subjects (90%). The most frequently reported AEs were mild/moderate nausea and diarrhoea. There were no serious AEs, discontinuations due to AEs, or deaths. CONCLUSIONS: Pegozafermin treatment for 20 weeks had beneficial effects on hepatic and metabolic parameters and was well tolerated in subjects with NASH. CLINICALTRIALS: gov: NCT04048135.

Adenoma Detection Rate Benchmarks: An Updated Analysis.

Early-onset colorectal cancer prompted organizations to reduce the recommended screening initiation age from 50 to 45 years. The American Society for Gastrointestinal Endoscopy Quality Assurance in Endoscopy Committee recommends 3 priority quality indicators for colonoscopy services. The adenoma detection rate is considered the most important measure with the established benchmark based upon studies of patients 50 years or older. The incidence of polyps increases with age, so this change has an as-yet-unknown effect on the new benchmark. Five studies were reviewed. Based upon the results, 45- to 50-year-old patients should be included in facilities' adenoma detection rate calculations using the currently recommended benchmarks of 25% for women and men combined, or 20% for women and 30% for men when the genders are calculated separately. Males consistently had more adenomas than females in each of the 3 studies that separated genders, a detail that might merit gender-based adenoma detection rate determinations in some practices. One study indicated caution is advised; it recommends males and females be calculated separately and different benchmarks be used for each gender. The adenoma detection rate has been shown to increase over time. More studies are needed to guide screening quality metrics.

Safety, pharmacokinetics, and pharmacodynamics of pegozafermin in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 1b/2a multiple-ascending-dose study.

BACKGROUND: Management strategies for non-alcoholic steatohepatitis (NASH) are based predominantly on lifestyle modification, with no approved disease-modifying drugs yet available. We aimed to evaluate the safety, pharmacokinetics, and pharmacodynamics of pegozafermin (BIO89-100), a glycoPEGylated FGF21 analogue, in participants with NASH. METHODS: This randomised, double-blind, placebo-controlled, phase 1b/2a multiple-ascending-dose study enrolled adults (aged 21-75 years) who had NASH with stage F1-F3 fibrosis, or non-alcoholic fatty liver disease and a high risk of NASH (referred to in this study as phenotypic NASH) due to central obesity with type 2 diabetes, or central obesity with increased alanine aminotransferase (ALT) or a Fibroscan score of 7 kPa or greater, across 12 specialist centres and clinics in the USA. Patients were centrally randomised by use of an interactive web response system to receive subcutaneously administered pegozafermin (3, 9, 18, or 27 mg once weekly; 18 or 36 mg once every 2 weeks) or placebo for 12 weeks. The primary endpoints were the safety, tolerability, and pharmacokinetics of pegozafermin. This trial is registered with ClinicalTrials.gov (NCT04048135). FINDINGS: Between July 29, 2019, and Aug 3, 2020, 275 participants were screened and 81 (15 [19%] with biopsy-confirmed NASH) were randomly assigned: 62 to pegozafermin (six to 3 mg once weekly, 12 to 9 mg once weekly, 11 to 18 mg once weekly, ten to 27 mg once weekly, 14 to 18 mg once every 2 weeks, and nine to 36 mg once every 2 weeks) and 19 to placebo; 63 received pegozafermin and 18 received placebo, as one participant in the placebo group inadvertently received 3 mg pegozafermin once weekly. Adverse events were reported in eight (44%) of 18 participants in the pooled placebo group, six (86%) of seven in the 3 mg once weekly pegozafermin group, four (33%) of 12 in the 9 mg once weekly group, seven (64%) of 11 in the 18 mg once weekly group, seven (70%) of ten in the 27 mg once weekly group, eight (57%) of 14 in the 18 mg once every 2 weeks group, and eight (89%) of nine in the 36 mg once every 2 weeks group. The most common treatment-related adverse event was mild increased appetite (in ten [16%] of 63 participants in the pooled pegozafermin group vs none of 18 in the pooled placebo group), which was not associated with bodyweight gain. Two patients discontinued treatment due to an adverse event (one each in the 27 mg once weekly and 18 mg once every 2 weeks groups). No treatment-related serious adverse events or deaths occurred. Dose-proportional pharmacokinetics were observed. Anti-drug antibodies were detected in 41 (65%) of 63 participants treated with pegozafermin. By week 13, pegozafermin significantly reduced the least squares mean (LSM) absolute differences in hepatic fat fraction versus pooled placebo (-8·9% [95% CI -14·8 to -3·1; p=0·0032] for 3 mg once weekly, -11·5% [-16·1 to -6·9; p<0·0001] for 9 mg once weekly, -8·9% [-13·7 to -4·2; p=0·0004] for 18 mg once weekly, -14·9% [-20·1 to -9·7; p<0·0001] for 27 mg once weekly, -10·4% [-14·7 to -6·1; p<0·0001] for 18 mg once every 2 weeks, and -11·1% [-16·2 to -6·0; p<0·0001] for 36 mg once every 2 weeks). At week 13, significant LSM relative reductions versus pooled placebo in ALT were observed for pegozafermin 9 mg once weekly, 18 mg once weekly, 27 mg once weekly, and 36 mg once every 2 weeks. At week 13, significant LSM relative reductions versus pooled placebo in aspartate aminotransferase were observed for pegozafermin 3 mg once weekly, 27 mg once weekly, and 36 mg once every 2 weeks. Significant improvements were also observed with pegozafermin treatment for triglycerides (9 mg once weekly, 27 mg once weekly, and 18 mg once every 2 weeks), LDL-C (9 mg once weekly and 27 mg once weekly), HDL-C (3 mg once weekly and 18 mg once every 2 weeks), non-HDL-C (9 mg once weekly and 27 mg once weekly), adiponectin (all doses except for 36 mg once every 2 weeks), PRO-C3 (27 mg once weekly), and bodyweight (27 mg once weekly). Changes in insulin resistance and HbA1c were not significant. INTERPRETATION: Pegozafermin was generally well tolerated and associated with clinically meaningful reductions in liver fat, measures of liver function, and circulating lipids. Further evaluation of pegozafermin in individuals with NASH is warranted. FUNDING: 89bio.

The American Society for Gastrointestinal Endoscopy Quality Assurance in Endoscopy Committee's Three Priority Quality Indicators for Screening Colonoscopy Services.

Colorectal cancer is the third most commonly diagnosed cancer in men and women in the United States. Small polyps are slow to grow and turn to cancer, which provides time for screening and removal of the precancerous polyps so that colorectal cancer is prevented. Quality colonoscopy services are essential to ensure all polyps are found and removed as the final step of colorectal cancer screening. The American Society for Gastrointestinal Endoscopy Quality Assurance in Endoscopy Committee developed quality indicators for colonoscopy services. The Committee prioritized 3 quality indicators for screening colonoscopies: the frequency of (1) adenoma detection in asymptomatic patients at average risk; (2) adherence to the surveillance intervals for postpolypectomy, postcancer resection, or the 10-year interval for the average-risk patients with good bowel preparations who had negative colonoscopies; and (3) visualization of the cecum by notation and landmark photographic documentation. Gastroenterology nurses, endoscopists, and the quality management team can use the Plan-Do-Study-Act method of quality improvement to meet the established performance targets and prevent interval cancers.

The American College of Gastroenterology's 2021 Colorectal Cancer Screening Guidelines: A Summary for Gastroenterology Nurses & Associates.

Colorectal cancer ranks third for both men and women as the most common cause of cancer death in the United States. Screening allows for removal of polyps before they turn to cancer or by identifying early-stage colorectal cancers, which are most treatable. The American College of Gastroenterology recently released an update of their 2009 recommendations, which includes average risk individuals between ages 45 and 49 years due to the increased incidence of early-onset colorectal cancers. They consider screening two types of screening options: (1) one-step colonoscopy, which is both diagnostic and therapeutic and (2) two-step options, all of which require a follow-up colonoscopy when the first step is positive. They added the recommendation of daily aspirin for some people aged 50 to 69 years. However, the recommendations for screening remain the same when people do take aspirin. They recommend endoscopists measure cecal intubation rates, adenoma detection rates, and withdrawal times to reduce postcolonoscopy cancers due to missed lesions. They also propose strategies to promote screening adherence and suggest health systems adopt them. These are important updates of which the gastroenterology nurse should be aware and assist with their implementation.

A Randomized, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Novel Insulin Dimer.

Insulin molecules of size much greater than natural insulin have been synthesized and studied with the intention of widening the therapeutic window between adequate glycemic control and hypoglycemia as compared with conventional insulins. MK-1092 is a synthetic insulin dimer with favorable properties demonstrated in preclinical studies. Here, we report the results of the first-in-human, randomized, double-blind, active-control, single ascending dose trial of MK-1092, conducted in healthy adults, adults with type 1 diabetes (T1D), and adults with type 2 diabetes (T2D). MK-1092 was well tolerated in all study populations, and no dose-related adverse events were identified across the evaluated dose range (4-64 nmol/kg). Circulating concentrations of MK-1092 were approximately dose-proportional. Maximum glucose infusion rate (GIR) and 24-hour time-weighted average GIR were evaluated under euglycemic clamp conditions. These pharmacodynamic measurements were approximately dose-proportional in all study populations; at similar doses, the GIR parameters were lower in adults with T2D than in healthy adults or adults with T1D, likely due to the influence of insulin resistance. At doses ≥ 16 nmol/kg, MK-1092 had similar or greater effects than glargine 3 nmol/kg (0.5 units/kg) on increasing GIR in each study population and on suppressing free fatty acids and ketone generation in adults with T1D. MK-1092 did not prevent a subsequent high dose of lispro from increasing the GIR in healthy adults. Additional studies in adults with T1D and T2D are needed to further evaluate the safety, tolerability, and efficacy profile of MK-1092 and its potential for differentiation from more conventional insulins. (ClinicalTrials.gov: NCT03170544).

Healthy Food Choices, Physical Activity, and Screening Reduce the Risk of Colorectal Cancer.

Cancer is the second leading cause of death in the United States with an estimated 1,806,590 new cases and 606,520 deaths in 2020. Cancer is a public health concern due to the numbers of cases, financial costs, and morbidity and mortality rates. An estimated 42% of all diagnosed cancers and 45% of cancer deaths in the United States in 2014 could be attributed to modifiable risk factors. Colorectal cancer screening is effective because small polyps take years to grow and turn to cancers allowing for early detection and removal of precancerous polyps. Primary prevention of colorectal cancer by risk factor reduction is also effective as these factors cause over half of colorectal cancer cases and deaths. Physical activity, weight control, healthy dietary choices, and abstinence from alcohol and tobacco are protective. The gastroenterology nurse can assess physical activity and food choices as vital signs and recommend a gradual addition of physical activity and a more plant-based diet with reduced processed food. All nurses need to advocate for policy improvements per our pledge to the Code of Ethics for Nurses. Policy changes improve the health of large numbers of people and make healthy behaviors a normalized way of life.

Incorporating protein precipitation to resolve hybrid IP-LC-MS assay interference for ultrasensitive quantification of intact therapeutic insulin dimer in human plasma.

For pharmacokinetics characterization of a therapeutic insulin dimer, an ultrasensitive plasma method was required due to the expected low circulating levels in humans. A bioanalytical strategy combining immunoprecipitation enrichment with liquid chromatography - tandem mass spectrometry (LC-MS/MS) analysis of the intact protein offers the opportunity to resolve the analyte from endogenous and exogenous insulin and insulin analogs. Nonetheless, interference from complex background matrix was observed limiting reliable measurements at the low concentration range. A sample preparation approach incorporating protein precipitation and immunoprecipitation was developed and optimized to further reduce sample complexity prior to LC-MS/MS analysis. This approach enabled a deeper level of selectivity and presented a cleaner mass spectrometric detection that may otherwise be confounded. Sample preparation was automated to allow high throughput analysis. The method reached a limit of quantitation at 0.3 ng/mL (25 pM), and a linear dynamic range from 0.3 to 300 ng/mL. Results were highly reproducible, with intra-day and inter-day precision and bias below 11%. Furthermore, the organic solvent treatment involved in protein precipitation is expected to improve assay resistance to the bias introduced by endogenous protein binding such as that exerted by anti-drug antibodies. The method was successfully applied to support clinical pharmacokinetics studies. This approach may potentially be adapted to bioanalysis of low abundance proteins.

Pharmacokinetics and Pharmacodynamics of Human Regular U-500 Insulin Administered via Continuous Subcutaneous Insulin Infusion Versus Subcutaneous Injection in Adults With Type 2 Diabetes and High-Dose Insulin Requirements.

INTRODUCTION: Human regular U-500 insulin (U-500R) is approved for subcutaneous (SC) injection in patients with diabetes requiring >200 units/day of insulin. Here, pharmacokinetic and pharmacodynamic (PK/PD) profiles following U-500R administered by continuous subcutaneous insulin infusion (CSII) and SC injection in adults with type 2 diabetes (T2D) on high-dose insulin were studied. METHODS: In this randomized, crossover, euglycemic clamp study, patients received a 100-unit bolus of U-500R via SC injection or CSII with basal infusion using a U-500R specific pump. PK parameters were estimated using non-compartmental methods. PD estimates were derived from the glucose infusion rate during the euglycemic clamp procedure. RESULTS: When corrected for the basal infusion, the PK profiles for the 100-unit bolus of U-500R were similar for CSII and SC injection. Without correction for basal infusion, PK and PD profiles showed a greater insulin concentration and effect when U-500R was administered via CSII compared to SC injection, primarily due to basal insulin infusion for CSII. The ratio of geometric least squares AUC0-tlast means SC:CSII (90% CI) is 0.857 (0.729, 1.01) with correction (mean AUC0-tlast: 5230 pmol*L/h [SC injection] and 6070 pmol*L/h [CSII, with correction]) and 0.424 (0.361, 0.499) without correction (mean AUC0-tlast: 12300 pmol*L/h [CSII, without correction]). Median time-to-peak insulin concentration was six hours (range 0.5-8 hours) via SC injection and five hours (0.5-12 hours) via CSII. CONCLUSIONS: In adults with T2D on high-dose insulin, U-500R PK/PD parameters were similar for a 100-unit bolus when given by SC injection or CSII via a U-500R pump.

Insulin and glucose metabolism with olanzapine and a combination of olanzapine and samidorphan: exploratory phase 1 results in healthy volunteers.

A combination of olanzapine and samidorphan (OLZ/SAM) received US Food and Drug Administration approval in May 2021 for the treatment of adults with schizophrenia or bipolar I disorder. OLZ/SAM provides the efficacy of olanzapine, while mitigating olanzapine-associated weight gain. This exploratory study characterized the metabolic profile of OLZ/SAM in healthy volunteers to gain mechanistic insights. Volunteers received once-daily oral 10 mg/10 mg OLZ/SAM, 10 mg olanzapine, or placebo for 21 days. Assessments included insulin sensitivity during an oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, other measures of glucose/lipid metabolism, and adverse event (AE) monitoring. Treatment effects were estimated with analysis of covariance. In total, 60 subjects were randomized (double-blind; placebo, n = 12; olanzapine, n = 24; OLZ/SAM, n = 24). Olanzapine resulted in hyperinsulinemia and reduced insulin sensitivity during an OGTT at day 19, changes not observed with OLZ/SAM or placebo. Insulin sensitivity, measured by hyperinsulinemic-euglycemic clamp, was decreased in all treatment groups relative to baseline, but this effect was greatest with olanzapine and OLZ/SAM. Although postprandial (OGTT) glucose and fasting cholesterol concentrations were similarly increased with olanzapine or OLZ/SAM, other early metabolic effects were distinct, including post-OGTT C-peptide concentrations and aspects of energy metabolism. Forty-nine subjects (81.7%) experienced at least 1 AE, most mild or moderate in severity. OLZ/SAM appeared to mitigate some of olanzapine's unfavorable postprandial metabolic effects (e.g., hyperinsulinemia, elevated C-peptide) in this exploratory study. These findings supplement the body of evidence from completed or ongoing OLZ/SAM clinical trials supporting its role in the treatment of schizophrenia and bipolar I disorder.

Effects of efpeglenatide versus liraglutide on gastric emptying, glucose metabolism and beta-cell function in people with type 2 diabetes: an exploratory, randomized phase Ib study.

INTRODUCTION: To evaluate the effects of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), on gastric emptying, glucose metabolism, and islet beta-cell function versus liraglutide and placebo in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: This phase Ib study (ClinicalTrials.gov identifier: NCT02059564) randomized participants (n=47) to three cohorts. Within the first two cohorts, participants were randomized to placebo, efpeglenatide 6 mg weekly (QW; first cohort), or efpeglenatide 16 mg monthly (QM; second cohort). The third cohort received liraglutide 1.8 mg daily (QD). Gastric emptying was assessed through the pharmacokinetic (PK) profile of acetaminophen at baseline and steady state. Glucose metabolism and beta-cell function were assessed based on mixed-meal tolerance testing and a graded glucose infusion procedure. RESULTS: Treatment duration was approximately 3 months for efpeglenatide 16 mg QM and 1 month for efpeglenatide 6 mg QW and liraglutide. At peak drug concentrations, efpeglenatide 6 mg QW was non-inferior to liraglutide 1.8 mg QD in delaying gastric emptying, as assessed by acetaminophen PK (lower bound of 90% CI for the efpeglenatide:liraglutide ratio >0.8 for area under the curve (AUC)0-120, AUC0-180, AUC0-360 and maximum concentration (Cmax)). Efpeglenatide 16 mg QM did not decrease the rate of gastric emptying to as great an extent as liraglutide (ie, non-inferiority was not shown). Compared with liraglutide, both efpeglenatide dosing regimens demonstrated comparable or more favorable glucometabolic effects and improved beta-cell function. All gastrointestinal adverse events reported with efpeglenatide were mild or moderate in severity and transient over treatment and follow-up. CONCLUSIONS: The glucometabolic effects of efpeglenatide 6 mg QW and 16 mg QM were comparable to liraglutide. Additional studies are necessary to further examine these benefits of efpeglenatide. TRIAL REGISTRATION NUMBER: NCT02059564.

Colorectal Cancer Survivors: How Gastroenterology Nurses Can Help Them Thrive.

Overall cancer death rates have fallen since a peak in 1991 due to declining death rates for lung, colorectal, breast, and prostate cancers. A "cancer survivor" is defined as anyone with a cancer diagnosis. Their numbers are increasing for several reasons including better screening, earlier detection, and improved treatments. The American Cancer Society's projections for colorectal cancer in 2020 are 147,950 new cases and 53,200 deaths. By 2024, there will be an estimated 1.71 million colorectal cancer survivors (17% of all cancer survivors) and many will experience long-term consequences. These problems may be the result of one or more treatment options: surgical resection, systemic chemotherapy, and radiation therapy. Problems include issues with bowel, ostomy, bladder, sexual health, peripheral neuropathy, and mental health. Colorectal cancer survivors are especially receptive to making lifestyle changes to improve their long-term health. Gastroenterology nurses can utilize evidence-based recommendations for weight management, diet, physical activity, and lifestyle with the goal of preventing recurrence and a second primary cancer and promoting overall long-term health.

Inhibition of fatty acid synthase with FT-4101 safely reduces hepatic de novo lipogenesis and steatosis in obese subjects with non-alcoholic fatty liver disease: Results from two early-phase randomized trials.

AIMS: To assess the therapeutic potential of fatty acid synthase (FASN) inhibition with FT-4101, a potent, selective, orally bioavailable, small-molecule by (a) evaluating the dose-response of single FT-4101 doses (3, 6 and 9 mg) on hepatic de novo lipogenesis (DNL) in healthy participants (Study 1) and (b) demonstrating the safety, tolerability and efficacy on hepatic steatosis after 12 weeks of FT-4101 dosing in patients with non-alcoholic fatty liver disease (NAFLD; Study 2). MATERIALS AND METHODS: In Study 1, three sequential cohorts of healthy men (n = 10/cohort) were randomized to receive a single dose of FT-4101 (n = 5/cohort) or placebo (n = 5/cohort) followed by crossover dosing after 7 days. Hepatic DNL was assessed during fructose stimulation from 13 C-acetate incorporation. In Study 2, men and women with NAFLD (n = 14) randomly received 12 weeks of intermittent once-daily dosing (four cycles of 2 weeks on-treatment, followed by 1 week off-treatment) of 3 mg FT-4101 (n = 9) or placebo (n = 5). Steady-state DNL based on deuterated water labelling, hepatic steatosis using magnetic resonance imaging-proton density fat fraction and sebum lipids and circulating biomarkers were assessed. RESULTS: Single and repeat dosing of FT-4101 were safe and well tolerated. Single FT-4101 doses inhibited hepatic DNL dose-dependently. Twelve weeks of 3 mg FT-4101 treatment improved hepatic steatosis and inhibited hepatic DNL. Decreases in sebum sapienate content with FT-4101 at week 11 were not significant compared to placebo and rebounded at week 12. Biomarkers of liver function, glucose and lipid metabolism were unchanged. CONCLUSIONS: Inhibition of FASN with 3 mg FT-4101 safely reduces hepatic DNL and steatosis in NAFLD patients.

Antibody-mediated activation of the FGFR1/Klothoß complex corrects metabolic dysfunction and alters food preference in obese humans.

Fibroblast growth factor 21 (FGF21) controls metabolic organ homeostasis and eating/drinking behavior via FGF receptor 1/Klothoß (FGFR1/KLB) complexes expressed in adipocytes, pancreatic acinar cells, and the nervous system in mice. Chronic administration of recombinant FGF21 or engineered variants improves metabolic health in rodents, nonhuman primates, and humans; however, the rapid turnover of these molecules limits therapeutic utility. Here we show that the bispecific anti-FGFR1/KLB agonist antibody BFKB8488A induced marked weight loss in obese cynomolgus monkeys while elevating serum adiponectin and the adipose expression of FGFR1 target genes, demonstrating its action as an FGF21 mimetic. In a randomized, placebo-controlled, single ascending-dose study in overweight/obese human participants, subcutaneous BFKB8488A injection caused transient body weight reduction, sustained improvement in cardiometabolic parameters, and a trend toward reduction in preference for sweet taste and carbohydrate intake. These data suggest that specific activation of the FGFR1/KLB complex in humans can be used as therapy for obesity-related metabolic defects.

How nurse practitioners can advocate for local, state, and federal policy to promote colorectal cancer prevention and screening.

ABSTRACT: Colorectal cancer (CRC) is the second most common cause of cancer deaths for men and women, combined, even though it is the most preventable, treatable, and beatable cancer. Polyp removal during colonoscopy is one major way to help prevent CRC, but it can also be prevented by modifiable risk factor reduction. The National Colorectal Cancer Roundtable's campaign "80% in Every Community" is an effort to address disparities in the less-screened populations and communities. The nurse practitioner (NP) can assist health care organizations to develop policies for high-quality screening programs and create system changes to promote CRC prevention and screening. Professional organizations provide an easy way to become involved in policy change at the health system, local, state, and federal levels. State and federal policies affect patient access to care and adherence to the CRC prevention and screening recommendations. Fourteen states have not yet elected to expand Medicaid. Every NP has the knowledge, skills, and ability to advocate for the expansion of Medicaid in these remaining states to reduce this access to care barrier for underserved patients and communities.

Improving the rate of colorectal cancer screening with the "80% in every community" campaign.

ABSTRACT: Colorectal cancer (CRC) ranks third in both cancer diagnoses and cancer-related deaths in men and women in the United States. Fortunately, both incidence and deaths have declined due to the increased use of CRC screening to find and remove precancerous polyps and to diagnose CRC at earlier, more treatable stages. Deaths from CRC have shifted to a new demographic, with a recent increase in incidence of 2% per year in people younger than 55 years. The American Cancer Society has issued a qualified recommendation that screening start at the age of 45 years because of this increase in early-onset CRC. There are multiple CRC screening test options. Professional organizations vary in their screening guidelines, but regardless of these differences, screening has been shown to save lives. Currently, one out of every three adults aged 50-75 years are not screened as recommended. The National Colorectal Cancer Roundtable (NCRCRT) has placed a high priority on screening people who remain unscreened. Nurse practitioners can improve the screening rates in outpatient clinics and health systems by adopting the campaign, "80% in Every Community," which has a goal to reduce disparities and improve screening rates in underserved and rural populations. The NCRCRT resources will help clinics and health systems reach the screening goal of 80% in every community.

The YSI 2300 Analyzer Replacement Meeting Report.

This is a summary report of the most important aspects discussed during the YSI 2300 Analyzer Replacement Meeting. The aim is to provide the interested reader with an overview of the complex topic and propose solutions for the current issue. This solution should not only be adequate for the United States or Europe markets but also for all other countries. The meeting addendum presents three outcomes of the meeting.

DNP Program Faculty and Graduates' Knowledge and Use of QI and Safety Processes.

BACKGROUND: Across doctor of nursing practice (DNP) programs, wide variation exists for DNP project expectations and curricular integration of Quality and Safety Education for Nurses competencies. PURPOSE: This study examined DNP project characteristics and compared knowledge, skills, and attitudes about quality improvement (QI) processes between DNP program faculty and graduates. METHODS: This descriptive study used a national convenience sample of DNP program faculty and graduates from multiple settings (N = 147) who completed an electronic survey of a modified version of the Quality Improvement Knowledge, Skills, and Attitudes Survey. RESULTS: Most DNP projects were QI/practice improvement (85.5%) and required interprofessional collaboration (65%) and implementation of a practice change (55.8%) with evaluation (65.5%). DNP program faculty (n = 73) and graduates (n = 30) had no significant differences in QI knowledge or skills; faculty reported less confidence in their knowledge (P = .002) and skills (P = .007) than graduates. CONCLUSIONS: Faculty development efforts to improve QI knowledge and skills for DNP program faculty are needed.

Sotagliflozin Decreases Postprandial Glucose and Insulin Concentrations by Delaying Intestinal Glucose Absorption.

CONTEXT: The effect of sotagliflozin (a dual sodium-glucose cotransporter [SGLT] 2 and SGLT1 inhibitor) on intestinal glucose absorption has not been investigated in humans. OBJECTIVE: To measure rate of appearance of oral glucose (RaO) using a dual glucose tracer method following standardized mixed meals taken after single sotagliflozin or canagliflozin doses. SETTING: Clinical research organization. DESIGN AND PARTICIPANTS: In a double-blind, 3-period crossover study (NCT01916863), 24 healthy participants were randomized to 2 cohorts of 12 participants. Within each cohort, participants were randomly assigned single oral doses of either sotagliflozin 400 mg, canagliflozin 300 mg, or placebo on each of test days 1, 8, and 15. On test days, Cohort 1 had breakfast containing [6,6-2H2] glucose 0.25 hours postdose and lunch containing [1-2H1] glucose 5.25 hours postdose; Cohort 2 had breakfast containing no labeled glucose 0.25 hours postdose and lunch containing [6,6-2H2] glucose 4.25 hours postdose. All participants received a 10- to 15-hour continuous [U-13C6] glucose infusion starting 5 hours before their first [6,6-2H2] glucose-containing meal. MAIN OUTCOME: RaO, postprandial glucose (PPG), and postprandial insulin. RESULTS: Sotagliflozin and canagliflozin decreased area under the curve (AUC)0-1 hour and/or AUC0-2 hours for RaO, PPG, and insulin after breakfast and/or the 4.25-hour postdose lunch (P < .05 versus placebo). After the 5.25-hour postdose lunch, sotagliflozin lowered RaO AUC0-1 hour and PPG AUC0-5 hours versus both placebo and canagliflozin (P < .05). CONCLUSIONS: Sotagliflozin delayed and blunted intestinal glucose absorption after meals, resulting in lower PPG and insulin levels, likely due to prolonged local inhibition of intestinal SGLT1 that persisted for ≥5 hours after dosing.