Early-life nutrition is associated with processing speed at age 5 in children born preterm with very low birth weight.

OBJECTIVE: Processing speed is suboptimal among preterm-born children which is of concern as it is a foundational skill supporting higher-level cognitive functions. The study objective was to evaluate associations between early-life nutrition and processing speed in childhood. METHODS: Macronutrient and human milk (mother's own, donor) intakes from 137 children born preterm with very low birth weight enrolled in a nutrition feeding trial were included. Processing speed was evaluated at age 5 using the WPPSI-IV Processing Speed Index. Associations between early-life nutrition and processing speed were explored through linear regression. RESULTS: Children had a mean (SD) birth gestational age of 28.1 (2.5) weeks, weight of 1036 (260) g and 52% were male. The mean (SD) assessment age was 5.7 (0.2) years. Sex-dependent relationships were identified between first postnatal month protein, lipid and energy intakes and processing speed at 5 years. For females, lower protein (per 0.1 g/kg/d: -0.88, 95% confidence interval [CI]: -1.53, -0.23; p = 0.01) and energy (per 10 kcal/kg/d: -2.38, 95% CI: -4.70, -0.05; p = 0.03) intakes were related to higher processing speed scores. Mother's milk provision was positively associated (per 10% increase: 0.80, 95% CI: 0.22, 1.37; p = 0.01) and donor milk was negatively associated (per 10% increase: -1.15, 95% CI: -2.22, -0.08; p = 0.04) with processing speed scores; no sex differences were observed. CONCLUSIONS: First postnatal month nutrition was related to processing speed at age 5 in children born preterm with very low birth weight. Early-life nutrition that supports processing speed may be leveraged to improve later cognitive outcomes for this vulnerable population.

Protein intake affects erythrocyte glutathione synthesis in healthy adults aged ≥60 years in a repeated-measures trial.

BACKGROUND: Protein recommendations for older adults are based on nitrogen balance data from young adults. Physiological studies using the indicator amino acid oxidation method suggest they need 30% to 50% more protein than current recommendations. We herein present glutathione (GSH) as a physiological estimate of protein adequacy in older adults. OBJECTIVES: The objective was to measure GSH kinetics in response to varying protein intakes in a repeated-measures design in healthy adults aged ≥60 y using the precursor-product method. METHODS: Sixteen healthy older adults (n = 8 male and n = 8 female; body mass index ≤30 kg/m2) were studied. Each received 4 of 6 protein intakes in random order (0.66, 0.8, 0.9, 1.1, 1.3 and 1.5 g⋅kg-1⋅d-1). At each intake level, participants underwent isotope infusion studies of 7 h duration following a 3-d adaptation to the test level of protein. On the fourth day, GSH fractional (FSR) and absolute synthesis (ASR) rates were quantified by measuring the incorporation of U-[13C2-15N]glycine into GSH at isotopic steady state. A mixed-effect change-point regression model was used to determine a breakpoint in FSR and ASR. Secondary outcomes included plasma concentrations of oxidative stress markers, homocysteine, 5-L-oxoproline (5-OP), and urinary sulfate. The effect of secondary outcomes on GSH kinetics was analyzed using a joint linear mixed-effect model and Tukey's post hoc test. RESULTS: A protein intake of 1.08 g⋅kg-1⋅d-1 (95% confidence interval [CI]: 0.83, 1.32; Rm2 = 0.207; Rc2 = 0.671; P < 0.001) maximized GSH FSR. There was no effect of protein intake on concentrations of erythrocyte GSH, plasma homocysteine, oxidative stress markers, or 5-OP (P > 0.05). Protein intake had a positive effect on urinary sulfate excretion (P < 0.0001). CONCLUSION: A protein intake of 1.08 g⋅kg-1⋅d-1 from a high-quality protein maximized GSH synthesis in adults ≥60 y. This lends support to data suggesting a requirement higher than the current recommendation. This study was registered at clinicaltrials.gov as NCT02971046.

Ethnicity data resource in population-wide health records: completeness, coverage and granularity of diversity.

Intersectional social determinants including ethnicity are vital in health research. We curated a population-wide data resource of self-identified ethnicity data from over 60 million individuals in England primary care, linking it to hospital records. We assessed ethnicity data in terms of completeness, consistency, and granularity and found one in ten individuals do not have ethnicity information recorded in primary care. By linking to hospital records, ethnicity data were completed for 94% of individuals. By reconciling SNOMED-CT concepts and census-level categories into a consistent hierarchy, we organised more than 250 ethnicity sub-groups including and beyond "White", "Black", "Asian", "Mixed" and "Other, and found them to be distributed in proportions similar to the general population. This large observational dataset presents an algorithmic hierarchy to represent self-identified ethnicity data collected across heterogeneous healthcare settings. Accurate and easily accessible ethnicity data can lead to a better understanding of population diversity, which is important to address disparities and influence policy recommendations that can translate into better, fairer health for all.

The Eyes Absent family members EYA4 and EYA1 promote PLK1 activation and successful mitosis through tyrosine dephosphorylation.

The Eyes Absent proteins (EYA1-4) are a biochemically unique group of tyrosine phosphatases known to be tumour-promoting across a range of cancer types. To date, the targets of EYA phosphatase activity remain largely uncharacterised. Here, we identify Polo-like kinase 1 (PLK1) as an interactor and phosphatase substrate of EYA4 and EYA1, with pY445 on PLK1 being the primary target site. Dephosphorylation of pY445 in the G2 phase of the cell cycle is required for centrosome maturation, PLK1 localization to centrosomes, and polo-box domain (PBD) dependent interactions between PLK1 and PLK1-activation complexes. Molecular dynamics simulations support the rationale that pY445 confers a structural impairment to PBD-substrate interactions that is relieved by EYA-mediated dephosphorylation. Depletion of EYA4 or EYA1, or chemical inhibition of EYA phosphatase activity, dramatically reduces PLK1 activation, causing mitotic defects and cell death. Overall, we have characterized a phosphotyrosine signalling network governing PLK1 and mitosis.

Comparison of major abdominal emergency surgery outcomes across organizational models of emergency surgical care: Analysis of the UK NELA national database.

BACKGROUND: Emergency general surgery (EGS) admissions account for a large proportion of surgical care and represent the majority of surgical patients who suffer in-hospital mortality. Health care systems continue to experience growing demand for emergency services: one way in which this is being increasingly addressed is dedicated subspecialty teams for emergency surgical admissions, most commonly termed "emergency general surgery" in the United Kingdom. This study aims to understand the impact of the emergency general surgery model of care on outcomes from emergency laparotomies. METHODS: Data was obtained from the National Emergency Laparotomy Audit database. Patients were dichotomized into EGS hospital or non-EGS hospital. Emergency general surgery hospital is defined as a hospital where >50% of in-hours emergency laparotomy operating is performed by an emergency general surgeon. The primary outcome was in-hospital mortality. Secondary outcomes were intensive therapy unit (ITU) length of stay and duration of hospital stay. A propensity score weighting approach was used to reduce confounding and selection bias. RESULTS: There were 115,509 patients from 175 hospitals included in the final analysis. The EGS hospital care group included 5,789 patients versus 109,720 patients in the non-EGS group. Following propensity score weighting, mean standardized mean difference reduced from 0.055 to <0.001. In-hospital mortality was similar (10.8% vs. 11.1%, p = 0.094), with mean length of stay (16.7 days vs. 16.1 days, p < 0.001) and ITU stay (2.8 days vs. 2.6 days, p < 0.001) persistently longer in patients treated in EGS systems. CONCLUSION: No significant association between the emergency surgery hospital model of care and in-hospital mortality in emergency laparotomy patients was seen. There is a significant association between the emergency surgery hospital model of care and an increased length of ITU stay and overall hospital stay. Further studies are required to examine the impact of changing models of EGS delivery in the United Kingdom. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Protein intake affects erythrocyte glutathione synthesis in young healthy adults in a repeated-measures trial.

BACKGROUND: In 2005, the Institute of Medicine advised using methods other than nitrogen balance (NB) for determining protein requirements. Since then, protein requirements using indicator amino acid oxidation (IAAO) have been published and are higher than NB. Glutathione (GSH), a tripeptide of cysteine, glutamate, and glycine, is a principal antioxidant that can be used as a functional indicator of protein adequacy. OBJECTIVES: The aim of this study was to measure changes in erythrocyte GSH kinetics [fractional synthesis rate (FSR) and absolute synthesis rate (ASR)] in healthy adults following a range of protein intakes at and above the current recommendations. METHODS: Sixteen healthy adults [8 males and 8 females, aged 25.6 ± 0.9 y (mean ± SEM)] were studied at 4 of 6 protein intakes ranging from 0.6 to 1.5 g⋅kg-1⋅d-1. Erythrocyte GSH kinetics were assessed during a 7-h infusion of [U-13C2-15N]glycine following 2 d of adaptation to each protein intake. Blood and urine tests were performed to measure oxidative stress markers, plasma homocysteine, triglycerides, plasma amino acid concentrations, 5-L-oxoproline (5-OP), and urinary sulfate. The protein intake that maximized GSH synthesis was determined using mixed-effect change-point regression in R. Primary and secondary outcomes were analyzed using linear mixed-effects and repeated-measures analysis of variance with Tukey's post hoc test. RESULTS: The protein intake that maximized GSH FSR at 78%⋅d-1 was 1.0 g⋅kg-1⋅d-1 (95% confidence interval: 0.63, 1.39). GSH ASR was significantly lower at 0.6 and 0.8 g⋅kg-1⋅d-1 than at 1.5 g⋅kg-1⋅d-1 (2.03 and 2.17, respectively, compared with 3.71 mmol⋅L-1⋅d-1). Increasing the protein intake led to increased urinary sulfate but did not affect erythrocyte GSH concentration, plasma oxidative stress markers, triglycerides, homocysteine, or 5-OP. CONCLUSIONS: A protein intake of 1.0 g⋅kg-1⋅d-1 maximized GSH synthesis, which is in agreement with earlier IAAO-derived protein requirements of 0.93 to 1.2 g⋅kg-1⋅d-1. These findings suggest that recommendations based on NB (0.66 g⋅kg-1⋅d-1) may underestimate protein needs for adequate health. This trial was registered at clinicaltrials.gov as NCT02971046.

Prescribing hand strengthening exercise for patients with rheumatoid arthritis; clinical cues influencing occupational therapists' and physiotherapists' judgements.

OBJECTIVE: To explore the clinical judgements of therapists in prescribing the intensity of hand strengthening exercise in rheumatoid arthritis (RA). METHODS: Phase I: Eleven therapists knowledgeable in treating patients with RA subjectively identified seven clinical cues. These were incorporated into 54 hypothetical patient case scenarios. PHASE II: Therapists with ≥2 years post-registration experience and current or recent experience in treating patients with RA were asked to assess 69 case scenarios in total (54 + 15 repeats) and judge what intensity of hand strengthening exercise they would prescribe using the OMNI-Resistance Exercise Scale of perceived exertion. Using responses to the repeated cases, the Cochran-Weiss-Shanteau index of expertise was used to identify therapists who prescribed more consistently. Multiple regression was used to determine which clinical cues were most strongly associated with the intensity of exercise prescribed. A sub-group analysis explored differences between consistent and inconsistent prescribers. RESULTS: Fifty-three therapists took part. Thirty completed all 69 case scenarios. Across all therapists, the three most important clinical cues associated with lower intensity of exercise prescribed were (1) Patient's reported pain intensity whilst practising the exercise (ß = -1.150, p < 0.001), (2) Disease activity (ß = -0.425, p < 0.001) and (3) average hand pain over the last week (ß = -0.353 p < 0.001). Twelve therapists were categorised as consistent prescribers. This group relied on fewer clinical cues (three vs. seven) when judging what intensity of exercise to prescribe. CONCLUSION: This study provides insights into how therapists prescribe hand exercises. Intensity of hand strengthening exercise was influenced by three key clinical cues, including pain intensity and disease activity.

Organ Donation in Canadian PICUs: A Cross-Sectional Survey, 2021-2022.

OBJECTIVES: To understand contemporary pediatric organ donation programs in Canadian PICUs, including: policies and practices, data collection and reporting, and system and process barriers. DESIGN: A cross-sectional survey carried out 2021-2022. SETTING: Canadian PICUs affiliated with a donor physician network. SUBJECTS: Pediatric intensivists identified as the donation program lead, or most knowledgeable about donation for their institution. MEASUREMENTS AND MAIN RESULTS: A 19-item survey was developed through collaboration with stakeholders from the organ donation and transplantation community within Canada. Domains and items were generated and reduced iteratively during an in-person workshop. Pretesting and pilot testing were completed to ensure readability, flow, clinical sensibility, and construct validity. Fifteen of 16 (94%) invited Canadian PICUs from seven provinces completed the survey representing 88% (15/18) of all noncardiac Canadian PICUs. Surveys were completed between June 2021 and September 2022. All units support donation after death by neurologic criteria (DNC); 14 of 15 indicated donation policies were in place and 1 of 15 indicated no policy but the ability to facilitate donation. Thirteen of 15 units (87%) support donation after death by circulatory criteria (DCC) with policies in place, with 11 of 13 of these indicating routine support of donation opportunities. The majority (13/15) of units identified a donation champion. Of the 16 identified champions across these centers, 13 were physicians and were registered nurses or nurse practitioners. Eight of 13 units (62%) with donation champions had positions supported financially, of which 5 units came from the Organ Donation Organization and the other 3 came from the provincial health authority. Finally, only 3 of 15 PICU donation programs have a pediatric donation committee with family involvement. Variability exists in identification (including determination of death practices), referral, and approach for donation between units. CONCLUSIONS: Although all Canadian PICUs support donation after DNC donation, and most support donation after DCC, variability exists in the identification, referral, and approach of potential donors. There is a notable lack of family involvement in pediatric donation programs. There are many opportunities for standardization of PICU donation programs which may result in improved rates of pediatric organ donation in Canada.

A Pilot Study of Family-Integrated Care (FICare) in Critically Ill Preterm and Term Infants in the NICU: FICare Plus.

Family-integrated care (FICare) is associated with improved developmental outcomes and decreased parental mental health risks in stable preterm infants. However, less is known about its application in critically ill infants who are at greater risk for adverse outcomes. The objective of this study was to assess the safety and feasibility of implementation of an augmented FICare program, FICare Plus, in critically ill infants in the first few weeks of life. Resources were specifically developed for staff and parents to support earlier parental engagement in infant care. Infant health outcomes and standardized measures of parental stress, anxiety and parenting self-efficacy were also collected using standardized questionnaires: State -Trait Anxiety Inventory (STAI), Parental Stressor Scale: NICU (PSS: NICU), Perceived Parenting Self-Efficacy Tool and Family Centered Care Survey. The t-test or Wilcoxon rank-sum test were used to compare continuous variables, while the Chi-square or Fisher exact test were used for categorical variables, respectively. In this prospective cohort study, 41 critically ill infants were enrolled: 17 in standard care (SC) and 24 in the FICare Plus group. The tools and procedures developed for FICare Plus successfully supported greater engagement in the care of their infants with no increase in adverse events and no increase in parental stress. Parents in the FICare Plus cohort felt confident to participate in their infant's care. The staff also found this model of care acceptable and well adopted. Preliminary measures of infant efficacy were similar in both groups. Total anxiety scores were high among all parents at enrollment (87 (67-94) vs. 70.5 (66-86); p-value 0.22). However, the scores prior to discharge were lower in FICare Plus group (78 (71-90) vs. 63 (52-74.5); p-value 0.02). This pilot study showed that it is feasible and safe to implement family-integrated care in critically ill infants.

Hospital admissions linked to SARS-CoV-2 infection in children and adolescents: cohort study of 3.2 million first ascertained infections in England.

OBJECTIVE: To describe hospital admissions associated with SARS-CoV-2 infection in children and adolescents. DESIGN: Cohort study of 3.2 million first ascertained SARS-CoV-2 infections using electronic health care record data. SETTING: England, July 2020 to February 2022. PARTICIPANTS: About 12 million children and adolescents (age <18 years) who were resident in England. MAIN OUTCOME MEASURES: Ascertainment of a first SARS-CoV-2 associated hospital admissions: due to SARS-CoV-2, with SARS-CoV-2 as a contributory factor, incidental to SARS-CoV-2 infection, and hospital acquired SARS-CoV-2. RESULTS: 3 226 535 children and adolescents had a recorded first SARS-CoV-2 infection during the observation period, and 29 230 (0.9%) infections involved a SARS-CoV-2 associated hospital admission. The median length of stay was 2 (interquartile range 1-4) days) and 1710 of 29 230 (5.9%) SARS-CoV-2 associated admissions involved paediatric critical care. 70 deaths occurred in which covid-19 or paediatric inflammatory multisystem syndrome was listed as a cause, of which 55 (78.6%) were in participants with a SARS-CoV-2 associated hospital admission. SARS-CoV-2 was the cause or a contributory factor in 21 000 of 29 230 (71.8%) participants who were admitted to hospital and only 380 (1.3%) participants acquired infection as an inpatient and 7855 (26.9%) participants were admitted with incidental SARS-CoV-2 infection. Boys, younger children (<5 years), and those from ethnic minority groups or areas of high deprivation were more likely to be admitted to hospital (all P<0.001). The covid-19 vaccination programme in England has identified certain conditions as representing a higher risk of admission to hospital with SARS-CoV-2: 11 085 (37.9%) of participants admitted to hospital had evidence of such a condition, and a further 4765 (16.3%) of participants admitted to hospital had a medical or developmental health condition not included in the vaccination programme's list. CONCLUSIONS: Most SARS-CoV-2 associated hospital admissions in children and adolescents in England were due to SARS-CoV-2 or SARS-CoV-2 was a contributory factor. These results should inform future public health initiatives and research.

A Methodological Framework for Assessing the Benefit of SARS-CoV-2 Vaccination following Previous Infection: Case Study of Five- to Eleven-Year-Olds.

Vaccination rates against SARS-CoV-2 in children aged five to eleven years remain low in many countries. The current benefit of vaccination in this age group has been questioned given that the large majority of children have now experienced at least one SARS-CoV-2 infection. However, protection from infection, vaccination or both wanes over time. National decisions on offering vaccines to this age group have tended to be made without considering time since infection. There is an urgent need to evaluate the additional benefits of vaccination in previously infected children and under what circumstances those benefits accrue. We present a novel methodological framework for estimating the potential benefits of COVID-19 vaccination in previously infected children aged five to eleven, accounting for waning. We apply this framework to the UK context and for two adverse outcomes: hospitalisation related to SARS-CoV-2 infection and Long Covid. We show that the most important drivers of benefit are: the degree of protection provided by previous infection; the protection provided by vaccination; the time since previous infection; and future attack rates. Vaccination can be very beneficial for previously infected children if future attack rates are high and several months have elapsed since the previous major wave in this group. Benefits are generally larger for Long Covid than hospitalisation, because Long Covid is both more common than hospitalisation and previous infection offers less protection against it. Our framework provides a structure for policy makers to explore the additional benefit of vaccination across a range of adverse outcomes and different parameter assumptions. It can be easily updated as new evidence emerges.

Metabolic acidosis during continuous glucagon therapy for neonatal hypoglycemia.

Objectives: Refractory neonatal hypoglycemia may be treated with glucagon infusions, which have been associated with thrombocytopenia and hyponatremia. After anecdotally noting metabolic acidosis during glucagon therapy in our hospital, an outcome not previously reported in the literature, we aimed to quantify occurrence of metabolic acidosis (base excess >-6) as well as thrombocytopenia and hyponatremia during treatment with glucagon. Methods: We performed a single-centre retrospective case series. Descriptive statistics were used and subgroups compared with Chi-Square, Fisher's Exact Test, and Mann-Whitney U testing. Results: Sixty-two infants (mean birth gestational age 37.2 weeks, 64.5% male) were treated with continuous glucagon infusions for median 10 days during the study period. 41.2% were preterm, 21.0% were small for gestational age, and 30.6% were infants of diabetic mothers. Metabolic acidosis was seen in 59.6% and was more common in infants who were not born to diabetic mothers (75% versus 24% in infants of diabetic mothers, P<0.001). Infants with versus without metabolic acidosis had lower birth weights (median 2,743 g versus 3,854 g, P<0.01) and were treated with higher doses of glucagon (0.02 versus 0.01 mg/kg/h, P<0.01) for a longer duration (12.4 versus 5.9 days, P<0.01). Thrombocytopenia was diagnosed in 51.9% of patients. Conclusions: In addition to thrombocytopenia, metabolic acidosis of unclear etiology appears to be very common with glucagon infusions for neonatal hypoglycemia, especially in lower birth weight infants or those born to mothers without diabetes. Further research is needed to elucidate causation and potential mechanisms.

The impact of the COVID-19 pandemic on cardiovascular disease prevention and management.

How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic.

Amino acid oxidation methods to determine amino acid requirements: do we require lengthy adaptation periods?

Determination of indispensable amino acid (IAA) requirements necessitates a range of intakes of the test IAA and monitoring of the physiological response. Short-term methods are the most feasible for studying multiple intake levels in the same individual. Carbon oxidation methods measure the excretion of 13CO2 in breath from a labelled amino acid (AA) in response to varying intakes of the test AA following a period of adaptation. However, the length of adaptation to each AA intake level has been a source of debate and disagreement among researchers. The assertion of the minimally invasive indicator amino acid oxidation (IAAO) technique is that IAA requirements can be estimated after only a few hours (8 h) of adaptation to each test AA intake, suggesting that adaptation occurs rapidly in response to dietary adjustments. On the contrary, the assertion of most other techniques is that 6-7 d of adaptation is required when determining IAA needs. It has even been argued that a minimum of two weeks is needed to achieve complete adaptation. This review explores evidence regarding AA oxidation methods and whether long periods of adaptation to test IAA levels are necessary when estimating IAA requirements. It was found that the consumption of experimental diets containing lower test IAA intake for greater than 7 d violates the terms of a successful adaptive response. While there is some evidence that short-term 8 h IAAO is not different among different test amino acid intakes up to 7 d, it is unclear whether it impacts assessment of IAA requirements.

An online randomised controlled trial of prognosticating imminent death in advanced cancer patients: Clinicians give greater weight to advice from a prognostic algorithm than from another clinician with a different profession.

BACKGROUND: A second opinion or a prognostic algorithm may increase prognostic accuracy. This study assessed the level to which clinicians integrate advice perceived to be coming from another clinician or a prognostic algorithm into their prognostic estimates, and how participant characteristics and nature of advice received affect this. METHODS: An online double-blind randomised controlled trial was conducted. Palliative doctors, nurses and other types of healthcare professionals were randomised into study arms differing by perceived source of advice (algorithm or another clinician). In fact, the advice was the same in both arms (emanating from the PiPS-B14 prognostic model). Each participant reviewed five patient summaries. For each summary, participants: (1) provided an initial probability estimate of two-week survival (0% 'certain death'-100% 'certain survival'); (2) received advice (another estimate); (3) provided a final estimate. Weight of Advice (WOA) was calculated for each summary (0 '100% advice discounting' - 1 '0% discounting') and multilevel linear regression analyses were conducted. CLINICAL TRIAL REGISTRATION NUMBER: NCT04568629. RESULTS: A total of 283 clinicians were included in the analysis. Clinicians integrated advice from the algorithm more than advice from another clinician (WOA difference = -0.12 [95% CI -0.18, -0.07], p < 0.001). There was no interaction between study arm and participant profession, years of palliative care or overall experience. Advice of intermediate strength (75%) was given a lower WOA (0.31) than advice received at either the 50% (WOA 0.40) or 90% level (WOA 0.43). The overall interaction between strength of advice and study arm on WOA was significant (p < 0.001). CONCLUSION: Clinicians adjusted their prognostic estimates more when advice was perceived to come from a prognostic algorithm than from another clinician. Research is needed to understand how clinicians make prognostic decisions and how algorithms are used in clinical practice.

Breastfeeding and human milk in the NICU: From birth to discharge.

It is well recognized that human milk is the optimal nutritive source for all infants, including those requiring intensive care. This statement reviews evidence supporting the importance of breastfeeding and human milk for infants, and why breastfeeding practices should be prioritized in the neonatal intensive care unit (NICU). It also reviews how to optimally feed infants based on their stability and maturity, and how to support mothers to establish and maintain milk production when their infants are unable to feed at the breast.

Association of COVID-19 With Major Arterial and Venous Thrombotic Diseases: A Population-Wide Cohort Study of 48 Million Adults in England and Wales.

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a prothrombotic state, but long-term effects of COVID-19 on incidence of vascular diseases are unclear. METHODS: We studied vascular diseases after COVID-19 diagnosis in population-wide anonymized linked English and Welsh electronic health records from January 1 to December 7, 2020. We estimated adjusted hazard ratios comparing the incidence of arterial thromboses and venous thromboembolic events (VTEs) after diagnosis of COVID-19 with the incidence in people without a COVID-19 diagnosis. We conducted subgroup analyses by COVID-19 severity, demographic characteristics, and previous history. RESULTS: Among 48 million adults, 125 985 were hospitalized and 1 319 789 were not hospitalized within 28 days of COVID-19 diagnosis. In England, there were 260 279 first arterial thromboses and 59 421 first VTEs during 41.6 million person-years of follow-up. Adjusted hazard ratios for first arterial thrombosis after COVID-19 diagnosis compared with no COVID-19 diagnosis declined from 21.7 (95% CI, 21.0-22.4) in week 1 after COVID-19 diagnosis to 1.34 (95% CI, 1.21-1.48) during weeks 27 to 49. Adjusted hazard ratios for first VTE after COVID-19 diagnosis declined from 33.2 (95% CI, 31.3-35.2) in week 1 to 1.80 (95% CI, 1.50-2.17) during weeks 27 to 49. Adjusted hazard ratios were higher, for longer after diagnosis, after hospitalized versus nonhospitalized COVID-19, among Black or Asian versus White people, and among people without versus with a previous event. The estimated whole-population increases in risk of arterial thromboses and VTEs 49 weeks after COVID-19 diagnosis were 0.5% and 0.25%, respectively, corresponding to 7200 and 3500 additional events, respectively, after 1.4 million COVID-19 diagnoses. CONCLUSIONS: High relative incidence of vascular events soon after COVID-19 diagnosis declines more rapidly for arterial thromboses than VTEs. However, incidence remains elevated up to 49 weeks after COVID-19 diagnosis. These results support policies to prevent severe COVID-19 by means of COVID-19 vaccines, early review after discharge, risk factor control, and use of secondary preventive agents in high-risk patients.

Human milk nutrient fortifiers alter the developing gastrointestinal microbiota of very-low-birth-weight infants.

Nutrient fortifiers are added to human milk to support the development of very-low-birth-weight infants. Currently, bovine-milk-based fortifiers (BMBFs) are predominantly administered, with increasing interest in adopting human-milk-based fortifiers (HMBFs). Although beneficial for growth, their effects on the gastrointestinal microbiota are unclear. This triple-blind, randomized clinical trial (NCT02137473) tested how nutrient-enriching human milk with HMBF versus BMBF affects the gastrointestinal microbiota of infants born < 1,250 g during hospitalization. HMBF-fed infants (n = 63, n = 269 stools) showed lower microbial diversity, altered microbial community structure, and changes in predicted microbial functions compared with BMBF-fed infants (n = 56, n = 239 stools). HMBF-fed infants had higher relative and normalized abundances of unclassified Enterobacteriaceae and lower abundances of Clostridium sensu stricto. Post hoc analyses identified dose-dependent relationships between individual feed components (volumes of mother's milk, donor milk, and fortifiers) and the microbiota. These results highlight how nutrient fortifiers impact the microbiota of very-low-birth-weight infants during a critical developmental window.

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records.

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK.