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Pyruvate kinase (PK) deficiency is a rare, hereditary, hemolytic anemia caused by mutations in the PKLR gene encoding the PK enzyme. Mitapivat (previously designated AG-348) is a first-in-class, oral, allosteric activator of PK. We report results from 5 Phase 1 trials in healthy adults to characterize and compare mitapivat pharmacokinetics across different formulations and analyze food effects on mitapivat bioavailability (Studies 1-5). Pharmacokinetic assessments were peak exposure, total exposure, time to maximum plasma concentration of mitapivat, and relative bioavailability (where appropriate). Plasma total exposure of mitapivat was similar in the fasted and fed (high-fat meal or different soft foods) states after capsule, tablet, and pediatric granule formulations. Although mitapivat administration with food reduced the rate of mitapivat absorption (delay in time to maximum plasma concentration; reduction in maximum concentration) versus dosing under fasted conditions, this was not considered clinically relevant, given the lack of effect on total mitapivat exposure. Consequently, the administration instructions for mitapivat relating to food state that "patients may take mitapivat tablets with or without food." These findings will continue to inform clinical studies and development of mitapivat in adult and pediatric patients with hemolytic anemias and may help inform healthcare professionals on mitapivat dosing/administration recommendations in clinical practice., (© 2024 The Author(s). Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Background: Malnutrition screening is not widely practiced in outpatient cancer centers. This review aims to determine the validity of malnutrition screening tools and provide recommendations for clinical use., Methods: Studies identified by a systematic review assessed the general validity of screening tools in adult oncology outpatients from five databases through 2022. The American Society for Parenteral and Enteral Nutrition (ASPEN) convened a working group of members from the Academy of Nutrition and Dietetics, Academy of Oncology Nurse and Patient Navigators, American Cancer Society, American Society for Clinical Oncology, American Society for Nutrition, American Society for Radiation Oncology, Association of Cancer Care Centers, and Oncology Nursing Society to answer the following questions: (1) should clinicians screen for malnutrition, (2) which malnutrition screening tools are recommended, and (3) what are the clinical applications for malnutrition risk screening in adult oncology outpatients?, Results: Twenty of 738 studies met the criteria and were reviewed. Six screening tools with specific cut-points demonstrated validity and are recommended, including the Mini Nutritional Assessment (≤23.5), Malnutrition Screening Tool (MST; MST ≥ 2 and patient-led MST ≥ 2), Malnutrition Universal Screening Tool (MUST; MUST ≥ 1 and MUST ≥ 2), Nutrition Risk Screening-2002 (NRS-2002; NRS-2002 ≥ 2 and NRS-2002 ≥ 3), NUTRISCORE ≥ 5, and Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF; PG-SGA SF ≥ 7 and PG-SGA SF ≥ 8)., Conclusion: Six screening tools are valid for malnutrition risk identification in oncology ambulatory settings and recommended before treatment initiation and regularly thereafter, depending on treatment course. Research is needed to understand to what extent early diagnosis and management of malnutrition improves the clinical care of oncology patients., (© 2024 The Author(s). Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: There is a large body of evidence evaluating quality improvement (QI) programmes to improve care for adults living with diabetes. These programmes are often comprised of multiple QI strategies, which may be implemented in various combinations. Decision-makers planning to implement or evaluate a new QI programme, or both, need reliable evidence on the relative effectiveness of different QI strategies (individually and in combination) for different patient populations., Objectives: To update existing systematic reviews of diabetes QI programmes and apply novel meta-analytical techniques to estimate the effectiveness of QI strategies (individually and in combination) on diabetes quality of care., Search Methods: We searched databases (CENTRAL, MEDLINE, Embase and CINAHL) and trials registers (ClinicalTrials.gov and WHO ICTRP) to 4 June 2019. We conducted a top-up search to 23 September 2021; we screened these search results and 42 studies meeting our eligibility criteria are available in the awaiting classification section., Selection Criteria: We included randomised trials that assessed a QI programme to improve care in outpatient settings for people living with diabetes. QI programmes needed to evaluate at least one system- or provider-targeted QI strategy alone or in combination with a patient-targeted strategy. - System-targeted: case management (CM); team changes (TC); electronic patient registry (EPR); facilitated relay of clinical information (FR); continuous quality improvement (CQI). - Provider-targeted: audit and feedback (AF); clinician education (CE); clinician reminders (CR); financial incentives (FI). - Patient-targeted: patient education (PE); promotion of self-management (PSM); patient reminders (PR). Patient-targeted QI strategies needed to occur with a minimum of one provider or system-targeted strategy., Data Collection and Analysis: We dual-screened search results and abstracted data on study design, study population and QI strategies. We assessed the impact of the programmes on 13 measures of diabetes care, including: glycaemic control (e.g. mean glycated haemoglobin (HbA1c)); cardiovascular risk factor management (e.g. mean systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), proportion of people living with diabetes that quit smoking or receiving cardiovascular medications); and screening/prevention of microvascular complications (e.g. proportion of patients receiving retinopathy or foot screening); and harms (e.g. proportion of patients experiencing adverse hypoglycaemia or hyperglycaemia). We modelled the association of each QI strategy with outcomes using a series of hierarchical multivariable meta-regression models in a Bayesian framework. The previous version of this review identified that different strategies were more or less effective depending on baseline levels of outcomes. To explore this further, we extended the main additive model for continuous outcomes (HbA1c, SBP and LDL-C) to include an interaction term between each strategy and average baseline risk for each study (baseline thresholds were based on a data-driven approach; we used the median of all baseline values reported in the trials). Based on model diagnostics, the baseline interaction models for HbA1c, SBP and LDL-C performed better than the main model and are therefore presented as the primary analyses for these outcomes. Based on the model results, we qualitatively ordered each QI strategy within three tiers (Top, Middle, Bottom) based on its magnitude of effect relative to the other QI strategies, where 'Top' indicates that the QI strategy was likely one of the most effective strategies for that specific outcome. Secondary analyses explored the sensitivity of results to choices in model specification and priors.  Additional information about the methods and results of the review are available as Appendices in an online repository. This review will be maintained as a living systematic review; we will update our syntheses as more data become available., Main Results: We identified 553 trials (428 patient-randomised and 125 cluster-randomised trials), including a total of 412,161 participants. Of the included studies, 66% involved people living with type 2 diabetes only. Participants were 50% female and the median age of participants was 58.4 years. The mean duration of follow-up was 12.5 months. HbA1c was the commonest reported outcome; screening outcomes and outcomes related to cardiovascular medications, smoking and harms were reported infrequently. The most frequently evaluated QI strategies across all study arms were PE, PSM and CM, while the least frequently evaluated QI strategies included AF, FI and CQI. Our confidence in the evidence is limited due to a lack of information on how studies were conducted.  Four QI strategies (CM, TC, PE, PSM) were consistently identified as 'Top' across the majority of outcomes. All QI strategies were ranked as 'Top' for at least one key outcome. The majority of effects of individual QI strategies were modest, but when used in combination could result in meaningful population-level improvements across the majority of outcomes. The median number of QI strategies in multicomponent QI programmes was three.  Combinations of the three most effective QI strategies were estimated to lead to the below effects:  - PR + PSM + CE: decrease in HbA1c by 0.41% (credibility interval (CrI) -0.61 to -0.22) when baseline HbA1c < 8.3%; - CM + PE + EPR: decrease in HbA1c by 0.62% (CrI -0.84 to -0.39) when baseline HbA1c > 8.3%;  - PE + TC + PSM: reduction in SBP by 2.14 mmHg (CrI -3.80 to -0.52) when baseline SBP < 136 mmHg; - CM + TC + PSM: reduction in SBP by 4.39 mmHg (CrI -6.20 to -2.56) when baseline SBP > 136 mmHg;  - TC + PE + CM: LDL-C lowering of 5.73 mg/dL (CrI -7.93 to -3.61) when baseline LDL < 107 mg/dL; - TC + CM + CR: LDL-C lowering by 5.52 mg/dL (CrI -9.24 to -1.89) when baseline LDL > 107 mg/dL. Assuming a baseline screening rate of 50%, the three most effective QI strategies were estimated to lead to an absolute improvement of 33% in retinopathy screening (PE + PR + TC) and 38% absolute increase in foot screening (PE + TC + Other)., Authors' Conclusions: There is a significant body of evidence about QI programmes to improve the management of diabetes. Multicomponent QI programmes for diabetes care (comprised of effective QI strategies) may achieve meaningful population-level improvements across the majority of outcomes. For health system decision-makers, the evidence summarised in this review can be used to identify strategies to include in QI programmes. For researchers, this synthesis identifies higher-priority QI strategies to examine in further research regarding how to optimise their evaluation and effects. We will maintain this as a living systematic review., (Copyright © 2023 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Background: Suboptimal transitions from the emergency department (ED) to ambulatory settings contribute to poor clinical outcomes and unnecessary nonurgent ED utilization. Care transition clinics (CTCs) are a potential solution by providing ED follow-up and facilitating the bridge to longer-term primary care., Objective: The objective was to evaluate the implementation of an ED transitions clinic on 30-day ED revisits and hospital readmissions., Designs: Retrospective cross-sectional study., Settings and Participants: This study included adults 18 years and older discharged from the ED and reeferred to the CTC., Main Outcome and Measures: Appointment attendance, follow-up time, and frequencies of care type provided were computed to assess clinic utilization. Rates of 30-day ED revisit and hospital admission were compared between completed and missed appointments using logistic regression., Results: Between March 2021 and March 2022, 373 patients were referred to the CTC totaling 405 appointments. Half (53%) of appointments were completed with a median follow-up time of 4 days (IQR = [2, 7]). The most common care types provided were wound care (44%) and clinical problem management (33%), with wound care appointments more likely to be completed compared with clinical appointments (OR = 1.7, CI = [1.1, 2.8], p = .03). Patients who completed their CTC appointment were 50% less likely to return to the ED in 30 days compared with those who did not complete their appointment (OR = 0.51, CI = [0.27, 0.98], p < .05). No effect was seen for CTC appointment completion on hospital readmission. Transition clinics are a viable method to provide timely access to follow-up for patients discharged from the ED and may help reduce excess ED use for ambulatory care needs., (© 2023 The Authors. Journal of Hospital Medicine published by Wiley Periodicals LLC on behalf of Society of Hospital Medicine.)

Background: Lipid-injectable emulsions (ILEs) are a necessity for neonates dependent on parenteral nutrition (PN). In this manuscript, we describe the patterns of ILE use in neonatal intensive care units (NICUs) in the United States (US)., Methods: An electronic survey was sent to 488 NICUs across the US between December 2020 and March 2021. Survey fields included availability and utilization of various ILE in neonates., Results: The response rate was 22% (107 out of 488). Soybean oil ILE (SO-ILE) and soybean oil, medium-chain triglycerides, olive oil, fish oil ILE (SO, MCT, OO, FO-ILE) had similar availability (87% vs 86%, respectively), and SO, MCT, OO, FO-ILE was more commonly used (SO-ILE, 71% vs SO, MCT, OO, FO-ILE, 86%). Fish oil-ILE (FO-ILE) was used by 55% of centers. SO-ILE was most frequently used with PN and needs <4 weeks without cholestasis (79%). The most common reason for SO, MCT, OO, FO-ILE use was cholestasis (71%). ILE minimization was used by 28% of SO-ILE and 22% of SO, MCT, OO, FO-ILE users; 95% of these centers restrict SO, MCT, OO, FO-ILE to doses ≤2 g/kg/day. Twenty-two percent of centers started FO-ILE at direct bilirubin of >5 mg/dl., Conclusion: The results of this survey reveal significant variability in ILE usage across the US. Lipid minimization with SO, MCT, OO, FO-ILE and initiation of FO-ILE for cholestasis at higher bilirubin thresholds are prevalent. Such reports are crucial for a better understanding of ILE use in the NICU and in future ILE development., (© 2022 American Society for Parenteral and Enteral Nutrition.)