St. John Hospital & Medical Center

BACKGROUND: Combination therapy with angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) decreases proteinuria; however, its safety and effect on the progression of kidney disease are uncertain. Methods We provided losartan (at a dose of 100 mg per day) to patients with type 2 diabetes, a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 300, and an estimated glomerular filtration rate (GFR) of 30.0 to 89.9 ml per minute per 1.73 m(2) of body-surface area and then randomly assigned them to receive lisinopril (at a dose of 10 to 40 mg per day) or placebo. The primary end point was the first occurrence of a change in the estimated GFR (a decline of ≥ 30 ml per minute per 1.73 m(2) if the initial estimated GFR was ≥ 60 ml per minute per 1.73 m(2) or a decline of ≥ 50% if the initial estimated GFR was <60 ml per minute per 1.73 m(2)), end-stage renal disease (ESRD), or death. The secondary renal end point was the first occurrence of a decline in the estimated GFR or ESRD. Safety outcomes included mortality, hyperkalemia, and acute kidney injury. Results The study was stopped early owing to safety concerns. Among 1448 randomly assigned patients with a median follow-up of 2.2 years, there were 152 primary end-point events in the monotherapy group and 132 in the combination-therapy group (hazard ratio with combination therapy, 0.88; 95% confidence interval [CI], 0.70 to 1.12; P=0.30). A trend toward a benefit from combination therapy with respect to the secondary end point (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P=0.10) decreased with time (P=0.02 for nonproportionality). There was no benefit with respect to mortality (hazard ratio for death, 1.04; 95% CI, 0.73 to 1.49; P=0.75) or cardiovascular events. Combination therapy increased the risk of hyperkalemia (6.3 events per 100 person-years, vs. 2.6 events per 100 person-years with monotherapy; P<0.001) and acute kidney injury (12.2 vs. 6.7 events per 100 person-years, P<0.001). Conclusions Combination therapy with an ACE inhibitor and an ARB was associated with an increased risk of adverse events among patients with diabetic nephropathy. (Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; VA NEPHRON-D ClinicalTrials.gov number, NCT00555217.).

BACKGROUND: Indications for cardiac-resynchronization therapy (CRT) in patients with heart failure include a prolonged QRS interval (> or =120 msec), in addition to other functional criteria. Some patients with narrow QRS complexes have echocardiographic evidence of left ventricular mechanical dyssynchrony and may also benefit from CRT. METHODS: We enrolled 172 patients who had a standard indication for an implantable cardioverter-defibrillator. Patients received the CRT device and were randomly assigned to the CRT group or to a control group (no CRT) for 6 months. The primary end point was the proportion of patients with an increase in peak oxygen consumption of at least 1.0 ml per kilogram of body weight per minute during cardiopulmonary exercise testing at 6 months. RESULTS: At 6 months, the CRT group and the control group did not differ significantly in the proportion of patients with the primary end point (46% and 41%, respectively). In a prespecified subgroup with a QRS interval of 120 msec or more, the peak oxygen consumption increased in the CRT group (P=0.02), but it was unchanged in a subgroup with a QRS interval of less than 120 msec (P=0.45). There were 24 heart-failure events requiring intravenous therapy in 14 patients in the CRT group (16.1%) and 41 events in 19 patients in the control group (22.3%), but the difference was not significant. CONCLUSIONS: CRT did not improve peak oxygen consumption in patients with moderate-to-severe heart failure, providing evidence that patients with heart failure and narrow QRS intervals may not benefit from CRT. (ClinicalTrials.gov number, NCT00132977 [ClinicalTrials.gov].).

Background: Chronic right ventricular pacing has been reported to promote cardiac dyssynchrony. The PAVE trial prospectively compared chronic biventricular pacing to right ventricular pacing in patients undergoing ablation of the AV node for management of atrial fibrillation with rapid ventricular rates. Methods and Results: One hundred and eighty‐four patients requiring AV node ablation were randomized to receive a biventricular pacing system (n = 103) or a right ventricular pacing system (n = 81). The study endpoints were change in the 6‐minute hallway walk test, quality of life, and left ventricular ejection fraction. Patient characteristics were similar (64% male; age: 69 ± 10 years, ejection fraction: 0.46 ± 0.16; 83%, NYHA Class II or III). At 6 months postablation, patients treated with cardiac resynchronization had a significant improvement in 6‐minute walk distance, (31%) above baseline (82.9 ± 94.7 m), compared to patients receiving right ventricular pacing, (24%) above baseline (61.2 ± 90.0 m) (P = 0.04). There were no significant differences in the quality‐of‐life parameters. At 6 months postablation, the ejection fraction in the biventricular group (0.46 ± 0.13) was significantly greater in comparison to patients receiving right ventricular pacing (0.41 ± 0.13, P = 0.03). Patients with an ejection fraction ≤45% or with NYHA Class II/III symptoms receiving a biventricular pacemaker appear to have a greater improvement in 6‐minute walk distance compared to patients with normal systolic function or Class I symptoms. Conclusion: For patients undergoing AV node ablation for atrial fibrillation, biventricular pacing provides a significant improvement in the 6‐minute hallway walk test and ejection fraction compared to right ventricular pacing. These beneficial effects of cardiac resynchronization appear to be greater in patients with impaired systolic function or with symptomatic heart failure.

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Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer related deaths in the world with an estimated number of 1.8 million new cases and about 881,000 deaths worldwide in 2018. The epidemiology of CRC varies significantly between different regions in the world as well as between different age, gender and racial groups. Multiple factors are involved in this variation, including risk factor exposure, demographic variations in addition to genetic susceptibility and genetic mutations and their effect on the prognosis and treatment response. In this mini-review, we discuss the recent epidemiological trend including the incidence and mortality of colorectal cancer worldwide and the factors affecting these trends.

BACKGROUND: The neurochemical and biological effects of antidepressant medications have become better defined over the last decade. When the anti-depressant bupropion was introduced in the United States in 1989, the specific pharmacologic basis of its clinical effects was uncertain. Research conducted over the past decade has significantly advanced the understanding of the neuropharmacology of bupropion and has demonstrated a novel mechanism of antidepressant activity. This article discusses the mechanism of action of bupropion and relates the drug's neuropharmacologic effects to its clinical efficacy and tolerability profiles. DATA SOURCES: Data were obtained via the MEDLINE database in an English-language search spanning the period 1965 to May 2002 and using the search terms bupropion, bupropion SR, and antidepressants, as well as from the manufacturer's bupropion databases. CONCLUSIONS: The preclinical and clinical data show that bupropion acts via dual inhibition of norepinephrine and dopamine reuptake and is devoid of clinically significant serotonergic effects or direct effects on postsynaptic receptors. Dual norepinephrine and dopamine reuptake inhibition is associated with a unique clinical profile. Bupropion has demonstrated efficacy comparable to that of other antidepressants. However, because bupropion is a selective norepinephrine and dopamine reuptake inhibitor with no serotonergic activity, common antidepressant-associated side effects, such as sexual dysfunction, weight gain, and sedation, are not associated with bupropion therapy.

IMPORTANCE: Since 2000, the incidence and severity of Clostridium difficile infection (CDI) have increased. OBJECTIVE: To review current evidence regarding best practices for the diagnosis and treatment of CDI in adults (age ≥ 18 years). EVIDENCE REVIEW: Ovid MEDLINE and Cochrane databases were searched using keywords relevant to the diagnosis and treatment of CDI in adults. Articles published between January 1978 and October 31, 2014, were selected for inclusion based on targeted keyword searches, manual review of bibliographies, and whether the article was a guideline, systematic review, or meta-analysis published within the past 10 years. Of 4682 articles initially identified, 196 were selected for full review. Of these, the most pertinent 116 articles were included. Clinical trials, large observational studies, and more recently published articles were prioritized in the selection process. FINDINGS: Laboratory testing cannot distinguish between asymptomatic colonization and symptomatic infection with C difficile. Diagnostic approaches are complex due to the availability of multiple testing strategies. Multistep algorithms using polymerase chain reaction (PCR) for the toxin gene(s) or single-step PCR on liquid stool samples have the best test performance characteristics (for multistep: sensitivity was 0.68-1.00 and specificity was 0.92-1.00; and for single step: sensitivity was 0.86-0.92 and specificity was 0.94-0.97). Vancomycin and metronidazole are first-line therapies for most patients, although treatment failures have been associated with metronidazole in severe or complicated cases of CDI. Recent data demonstrate clinical success rates of 66.3% for metronidazole vs 78.5% for vancomycin for severe CDI. Newer therapies show promising results, including fidaxomicin (similar clinical cure rates to vancomycin, with lower recurrence rates for fidaxomicin, 15.4% vs vancomycin, 25.3%; P = .005) and fecal microbiota transplantation (response rates of 83%-94% for recurrent CDI). CONCLUSIONS AND RELEVANCE: Diagnostic testing for CDI should be performed only in symptomatic patients. Treatment strategies should be based on disease severity, history of prior CDI, and the individual patient's risk of recurrence. Vancomycin is the treatment of choice for severe or complicated CDI, with or without adjunctive therapies. Metronidazole is appropriate for mild disease. Fidaxomicin is a therapeutic option for patients with recurrent CDI or a high risk of recurrence. Fecal microbiota transplantation is associated with symptom resolution of recurrent CDI but its role in primary and severe CDI is not established.

BACKGROUND: Catheter-associated urinary tract infections (CAUTI) are costly, common and often preventable by reducing unnecessary urinary catheter (UC) use. METHODS: To summarise interventions to reduce UC use and CAUTIs, we updated a prior systematic review (through October 2012), and a meta-analysis regarding interventions prompting UC removal by reminders or stop orders. A narrative review summarises other CAUTI prevention strategies including aseptic insertion, catheter maintenance, antimicrobial UCs, and bladder bundle implementation. RESULTS: 30 studies were identified and summarised with interventions to prompt removal of UCs, with potential for inclusion in the meta-analyses. By meta-analysis (11 studies), the rate of CAUTI (episodes per 1000 catheter-days) was reduced by 53% (rate ratio 0.47; 95% CI 0.30 to 0.64, p<0.001) using a reminder or stop order, with five studies also including interventions to decrease initial UC placement. The pooled (nine studies) standardised mean difference (SMD) in catheterisation duration (days) was -1.06 overall (p=0.065) including a statistically significant decrease in stop-order studies (SMD -0.37; p<0.001) but not in reminder studies (SMD, -1.54; p=0.071). No significant harm from catheter removal strategies is supported. Limited research is available regarding the impact of UC insertion and maintenance technique. A recent randomised controlled trial indicates antimicrobial catheters provide no significant benefit in preventing symptomatic CAUTIs. CONCLUSIONS: UC reminders and stop orders appear to reduce CAUTI rates and should be used to improve patient safety. Several evidence-based guidelines have evaluated CAUTI preventive strategies as well as emerging evidence regarding intervention bundles. Implementation strategies are important because reducing UC use involves changing well-established habits.

CONTEXT: Despite the growing popularity of bariatric surgery, there remain concerns about perioperative safety and variation in outcomes across hospitals. OBJECTIVE: To assess complication rates of different bariatric procedures and variability in rates of serious complications across hospitals and according to procedure volume and center of excellence (COE) status. DESIGN, SETTING, AND PATIENTS: Involving 25 hospitals and 62 surgeons statewide, the Michigan Bariatric Surgery Collaborative (MBSC) administers an externally audited, prospective clinical registry. We evaluated short-term morbidity in 15,275 Michigan patients undergoing 1 of 3 common bariatric procedures between 2006 and 2009. We used multilevel regression models to assess variation in risk-adjusted complication rates across hospitals and the effects of procedure volume and COE designation (by the American College of Surgeons or American Society for Metabolic and Bariatric Surgery) status. MAIN OUTCOME MEASURE: Complications occurring within 30 days of surgery. RESULTS: Overall, 7.3% of patients experienced perioperative complications, most of which were wound problems and other minor complications. Serious complications were most common after gastric bypass (3.6%; 95% confidence interval [CI], 3.2%-4.0%), followed by sleeve gastrectomy (2.2%; 95% CI, 1.2%-3.2%), and laparoscopic adjustable gastric band (0.9%; 95% CI, 0.6%-1.1%) procedures (P < .001). Mortality occurred in 0.04% (95% CI, 0.001%-0.13%) of laparoscopic adjustable gastric band, 0 sleeve gastrectomy, and 0.14% (95% CI, 0.08%-0.25%) of the gastric bypass patients. After adjustment for patient characteristics and procedure mix, rates of serious complications varied from 1.6% (95% CI, 1.3-2.0) to 3.5% (95% CI, 2.4-5.0) (risk difference, 1.9; 95% CI, 0.08-3.7) across hospitals. Average annual procedure volume was inversely associated with rates of serious complications at both the hospital level (< 150 cases, 4.1%; 95% CI, 3.0%-5.1%; 150-299 cases, 2.7%; 95% CI, 2.2-3.2; and > or = 300 cases, 2.3%; 95% CI, 2.0%-2.6%; P = .003) and surgeon level (< 100 cases, 3.8%; 95% CI, 3.2%-4.5%; 100-249 cases, 2.4%; 95% CI, 2.1%-2.8%; > or = 250 cases, 1.9%; 95% CI, 1.4%-2.3%; P = .001). Adjusted rates of serious complications were similar in COE and non-COE hospitals (COE, 2.7%; 95% CI, 2.5%-3.1%; non-COE, 2.0%; 95% CI, 1.5%-2.4%; P = .41). CONCLUSIONS: The frequency of serious complications among patients undergoing bariatric surgery in Michigan was relatively low. Rates of serious complications are inversely associated with hospital and surgeon procedure volume, but unrelated to COE accreditation by professional organizations.

Acinetobacter baumannii remains an important and difficult-to-treat pathogen whose resistance patterns result in significant challenges for the clinician. Despite the prevalence and interest in A. baumannii infections, there is relatively limited well-controlled scientific data to help the clinician select optimal empirical and subsequent targeted therapy for a variety of infections. We will review the currently available antimicrobial agents and discuss the clinical data supporting the use of the various agents.

OBJECTIVE: To systematically review the medical literature in order to determine the strength of the recommendation for screening and brief intervention (SBI) for alcohol-related problems in the emergency department (ED) setting. METHODS: The review followed the methodology of systematic reviews and was facilitated through the use of a structured template, a companion explanatory piece, and a grading and methodological scoring system based on published criteria for critical appraisal. The primary outcome measure was the prevention of mortality and morbidity secondary to alcohol-related illnesses/injuries. The secondary outcome measures included: decreased consumption; fewer ED/outpatient visits and hospitalizations; a decrease in social consequences; and increased referrals for follow-up and/or treatment. Three Medline searches as well as a search of the Cochrane Library were performed. Two team members reviewed the abstracts and selected pertinent articles. References were screened for additional pertinent articles. RESULTS: Twenty-seven articles were identified and reviewed, in addition to the 14 primary articles included in the 1996 U.S. Preventive Services Task Force Report. The study populations were diverse, including inpatient, outpatient, and college settings, with ages ranging from 12 to 70 years. Four studies were ED-based and two included EDs as one of multiple sites. Thirty-nine studies on SBI, 30 randomized controlled and nine cohort, were used to formulate the current recommendation. A positive effect of the intervention was demonstrated in 32 of these studies. CONCLUSIONS: The authors recommend that SBI for alcohol-related problems in the ED be incorporated into clinical practice.

At a crucial time with rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant globally, the United States Food and Drug Administration has issued an emergency use authorization for 2 oral antivirals, molnupiravir (in persons aged ≥18 years) and nirmatrelvir-ritonavir (Paxlovid) (in persons aged ≥12 years weighing ≥40 kg), for the outpatient treatment of patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at risk for progression. Molnupiravir is a nucleoside analogue, whereas nirmatrelvir is a SARS-CoV-2 main protease inhibitor, and ritonavir is a human immunodeficiency virus type 1 protease inhibitor. Drug interactions are a major concern for nirmatrelvir-ritonavir. Nirmatrelvir-ritonavir demonstrated a greater risk reduction in hospitalization and death than molnupiravir compared to placebo. Both drugs need to be started within 5 days of symptoms onset and given for 5 days' duration. This article reviews the 2 oral COVID-19 antiviral drugs including the mechanisms of action, antiviral activity, pharmacokinetics, drug interactions, clinical experience including trials, adverse events, recommended indications, and formulary considerations.

BACKGROUND: Catheter-associated urinary tract infection (UTI) is a common device-associated infection in hospitals. Both technical factors--appropriate catheter use, aseptic insertion, and proper maintenance--and socioadaptive factors, such as cultural and behavioral changes in hospital units, are important in preventing catheter-associated UTI. METHODS: The national Comprehensive Unit-based Safety Program, funded by the Agency for Healthcare Research and Quality, aimed to reduce catheter-associated UTI in intensive care units (ICUs) and non-ICUs. The main program features were dissemination of information to sponsor organizations and hospitals, data collection, and guidance on key technical and socioadaptive factors in the prevention of catheter-associated UTI. Data on catheter use and catheter-associated UTI rates were collected during three phases: baseline (3 months), implementation (2 months), and sustainability (12 months). Multilevel negative binomial models were used to assess changes in catheter use and catheter-associated UTI rates. RESULTS: Data were obtained from 926 units (59.7% were non-ICUs, and 40.3% were ICUs) in 603 hospitals in 32 states, the District of Columbia, and Puerto Rico. The unadjusted catheter-associated UTI rate decreased overall from 2.82 to 2.19 infections per 1000 catheter-days. In an adjusted analysis, catheter-associated UTI rates decreased from 2.40 to 2.05 infections per 1000 catheter-days (incidence rate ratio, 0.86; 95% confidence interval [CI], 0.76 to 0.96; P=0.009). Among non-ICUs, catheter use decreased from 20.1% to 18.8% (incidence rate ratio, 0.93; 95% CI, 0.90 to 0.96; P<0.001) and catheter-associated UTI rates decreased from 2.28 to 1.54 infections per 1000 catheter-days (incidence rate ratio, 0.68; 95% CI, 0.56 to 0.82; P<0.001). Catheter use and catheter-associated UTI rates were largely unchanged in ICUs. Tests for heterogeneity (ICU vs. non-ICU) were significant for catheter use (P=0.004) and catheter-associated UTI rates (P=0.001). CONCLUSIONS: A national prevention program appears to reduce catheter use and catheter-associated UTI rates in non-ICUs. (Funded by the Agency for Healthcare Research and Quality.).

BACKGROUND AND OBJECTIVES: Roxadustat (FG-4592), an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, regulates iron metabolism, and reduces hepcidin, was evaluated in this phase 2b study for safety, efficacy, optimal dose, and dose frequency in patients with nondialysis CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The 145 patients with nondialysis CKD and hemoglobin ≤10.5 g/dl were randomized into one of six cohorts of approximately 24 patients each with varying roxadustat starting doses (tiered weight and fixed amounts) and frequencies (two and three times weekly) followed by hemoglobin maintenance with roxadustat one to three times weekly. Treatment duration was 16 or 24 weeks. Intravenous iron was prohibited. The primary end point was the proportion of patients achieving hemoglobin increase of ≥1.0 g/dl from baseline and hemoglobin of ≥11.0 g/dl by week 17 (16 weeks of treatment). Secondary analyses included mean hemoglobin change from baseline, iron utilization, and serum lipids. Safety was evaluated by frequency/severity of adverse events. RESULTS: Of the 145 patients enrolled, 143 were evaluable for efficacy. Overall, 92% of patients achieved hemoglobin response. Higher compared with lower starting doses led to earlier achievement of hemoglobin response. Roxadustat-induced hemoglobin increases were independent of baseline C-reactive protein levels and iron repletion status. Overall, over the first 16 treatment weeks, hepcidin levels decreased by 16.9% (P=0.004), reticulocyte hemoglobin content was maintained, and hemoglobin increased by a mean (±SD) of 1.83 (±0.09) g/dl (P<0.001). Overall mean total cholesterol level was reduced by a mean (±SD) of 26 (±30) mg/dl (P<0.001) after 8 weeks of therapy, independent of the use of statins or other lipid-lowering agents. No drug-related serious adverse events were reported. CONCLUSIONS: In patients with nondialysis CKD who were anemic, various starting dose regimens of roxadustat were well tolerated and achieved anemia correction with reduced serum hepcidin levels. After anemia correction, hemoglobin was maintained by roxadustat at various dose frequencies without intravenous iron supplementation.

BACKGROUND: Sepsis is a common condition encountered by emergency and critical care physicians, with significant costs, both economic and human. Myocardial dysfunction in sepsis is a well-recognized but poorly understood phenomenon. There is an extensive body of literature on this subject, yet results are conflicting and no objective definition of septic cardiomyopathy exists, representing a critical knowledge gap. OBJECTIVES: In this article, we review the pathophysiology of septic cardiomyopathy, covering the effects of key inflammatory mediators on both the heart and the peripheral vasculature, highlighting the interconnectedness of these two systems. We focus on the extant literature on echocardiographic and laboratory assessment of the heart in sepsis, highlighting gaps therein and suggesting avenues for future research. Implications for treatment are briefly discussed. CONCLUSIONS: As a result of conflicting data, echocardiographic measures of left ventricular (systolic or diastolic) or right ventricular function cannot currently provide reliable prognostic information in patients with sepsis. Natriuretic peptides and cardiac troponins are of similarly unclear utility. Heterogeneous classification of illness, treatment variability, and lack of formal diagnostic criteria for septic cardiomyopathy contribute to the conflicting results. Development of formal diagnostic criteria, and use thereof in future studies, may help elucidate the link between cardiac performance and outcomes in patients with sepsis.

BACKGROUND: Tight blood glucose control has been correlated with a reduction in diabetes complications. Adherence to antidiabetic medications is crucial to achieving blood glucose control. OBJECTIVE: To assess the relationship between good glucose control [glycosylated hemoglobin (HbA1c) levels] and adherence to prescribed treatment in patients on a stable medication regimen for type 2 diabetes. METHODS: The Morisky survey, a 4-item questionnaire that predicts patient medication-taking behavior, was used to assess adherence in 301 patients. The relationship of HbA1c to Morisky score was evaluated, controlling for other variables related to patient demographics and clinical characteristics. Data were analyzed using a general linear model on log (HbA1c). RESULTS: Unadjusted mean HbA1c values (capped at 14.0%) for patients with Morisky scores of 0 or 1, 2, 3, and 4 were 8.92%, 8.67%, 7.74%, and 7.60%, respectively. Of all patients, 13.0%, 14.0%, 24.3%, and 48.8% had scores of 0 or 1, 2, 3, and 4, respectively. Good adherence (Morisky score > or = 3) was associated with a 10% lower total HbA1c (p = 0.0003) adjusted for all other factors in the model. Duration of diabetes (5-10 y) and presence of diabetes complications were also significantly associated with HbA1c (p = 0.026 and 0.002, respectively). Adherence was poor in 27% of patients. CONCLUSIONS: This study found that patients with a higher score on the Morisky scale had a lower associated HbA1c measurement. The Morisky score may be an efficient tool for identifying patients with poor medication-taking behavior who can then be targeted for directed adherence counseling services.

OBJECTIVE: Münchausen by proxy syndrome (MBPS) is a form of child abuse in which a parent fabricates or produces illness in a child. Although the medical consequences of MBPS have been well described, there is no detailed published account of what it was like to grow up in a family where the mother systematically induced serious illness. This article describes one victim's childhood experiences. METHODS: The medical history was obtained from a review of the original medical records, notes from the primary physician, discussions with two physicians who provided treatment, and several meetings with the victim and the victim's therapist. RESULTS: This article chronicles the actual experiences of an MBPS victim through 8 years of medical abuse at the hands of her mother, reveals the victim's account of what happened to her, describes what her family was like, details the long-term consequences on emotional and physical development, identifies the factors that influence recovery, and details the impact on family relationships. CONCLUSIONS: Child maltreatment and MBPS need to be part of the differential diagnosis when the clinical picture is atypical or does not appear medically plausible. The consequences of MBPS are psychological and physical and impact the entire family. Suggestions to assist heath care providers recognize, assess, and report cases of suspected MBPS are provided.

BACKGROUND & AIMS: Artificial intelligence (AI) may detect colorectal polyps that have been missed due to perceptual pitfalls. By reducing such miss rate, AI may increase the detection of colorectal neoplasia leading to a higher degree of colorectal cancer (CRC) prevention. METHODS: Patients undergoing CRC screening or surveillance were enrolled in 8 centers (Italy, UK, US), and randomized (1:1) to undergo 2 same-day, back-to-back colonoscopies with or without AI (deep learning computer aided diagnosis endoscopy) in 2 different arms, namely AI followed by colonoscopy without AI or vice-versa. Adenoma miss rate (AMR) was calculated as the number of histologically verified lesions detected at second colonoscopy divided by the total number of lesions detected at first and second colonoscopy. Mean number of lesions detected in the second colonoscopy and proportion of false negative subjects (no lesion at first colonoscopy and at least 1 at second) were calculated. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted by endoscopist, age, sex, and indication for colonoscopy. Adverse events were also measured. RESULTS: A total of 230 subjects (116 AI first, 114 standard colonoscopy first) were included in the study analysis. AMR was 15.5% (38 of 246) and 32.4% (80 of 247) in the arm with AI and non-AI colonoscopy first, respectively (adjusted OR, 0.38; 95% CI, 0.23-0.62). In detail, AMR was lower for AI first for the ≤5 mm (15.9% vs 35.8%; OR, 0.34; 95% CI, 0.21-0.55) and nonpolypoid lesions (16.8% vs 45.8%; OR, 0.24; 95% CI, 0.13-0.43), and it was lower both in the proximal (18.3% vs 32.5%; OR, 0.46; 95% CI, 0.26-0.78) and distal colon (10.8% vs 32.1%; OR, 0.25; 95% CI, 0.11-0.57). Mean number of adenomas at second colonoscopy was lower in the AI-first group as compared with non-AI colonoscopy first (0.33 ± 0.63 vs 0.70 ± 0.97, P < .001). False negative rates were 6.8% (3 of 44 patients) and 29.6% (13 of 44) in the AI and non-AI first arms, respectively (OR, 0.17; 95% CI, 0.05-0.67). No difference in the rate of adverse events was found between the 2 groups. CONCLUSIONS: AI resulted in an approximately 2-fold reduction in miss rate of colorectal neoplasia, supporting AI-benefit in reducing perceptual errors for small and subtle lesions at standard colonoscopy. CLINICALTRIALS: gov, Number: NCT03954548.

BACKGROUND: Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin. STUDY DESIGN: Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study. SETTING & PARTICIPANTS: Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa. INTERVENTION: Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous epoetin alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of epoetin alfa responsiveness. Intravenous iron was prohibited. OUTCOMES: Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of -0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2). MEASUREMENTS: Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset). RESULTS: Baseline epoetin alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and epoetin alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the epoetin alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus epoetin alfa (P<0.05). In part 2, the average roxadustat dose requirement for Hb level maintenance was ∼1.7mg/kg. The least-squares-mean ΔHb in roxadustat-treated individuals was comparable to that in epoetin alfa-treated individuals (about -0.5g/dL) and the least-squares-mean difference in ΔHb between both treatment arms was -0.03 (95% CI, -0.39 to 0.33) g/dL (mixed effect model-repeated measure). Roxadustat significantly reduced mean total cholesterol levels, not observed with epoetin alfa. No safety concerns were raised. LIMITATIONS: Short treatment duration and small sample size. CONCLUSIONS: In this phase 2 study of anemia therapy in patients with end-stage renal disease on maintenance hemodialysis therapy, roxadustat was well tolerated and effectively maintained Hb levels.

CKD is a major risk factor for ESRD, cardiovascular disease, and premature death. Whether dietary sodium and potassium intake affect CKD progression remains unclear. We prospectively studied the association of urinary sodium and potassium excretion with CKD progression and all-cause mortality among 3939 patients with CKD in the Chronic Renal Insufficiency Cohort Study. Urinary sodium and potassium excretion were measured using three 24-hour urine specimens, and CKD progression was defined as incident ESRD or halving of eGFR. During follow-up, 939 CKD progression events and 540 deaths occurred. Compared with the lowest quartile of urinary sodium excretion (<116.8 mmol/24 h), hazard ratios (95% confidence intervals) for the highest quartile of urinary sodium excretion (≥194.6 mmol/24 h) were 1.54 (1.23 to 1.92) for CKD progression, 1.45 (1.08 to 1.95) for all-cause mortality, and 1.43 (1.18 to 1.73) for the composite outcome of CKD progression and all-cause mortality after adjusting for multiple covariates, including baseline eGFR. Additionally, compared with the lowest quartile of urinary potassium excretion (<39.4 mmol/24 h), hazard ratios for the highest quartile of urinary potassium excretion (≥67.1 mmol/24 h) were 1.59 (1.25 to 2.03) for CKD progression, 0.98 (0.71 to 1.35) for all-cause mortality, and 1.42 (1.15 to 1.74) for the composite outcome. These data indicate that high urinary sodium and potassium excretion are associated with increased risk of CKD progression. Clinical trials are warranted to test the effect of sodium and potassium reduction on CKD progression.