The impact of packaging attributes on portion decisions: Consumer values are important.

Research shows that features of food packaging can help to promote healthy food choices. Laboratory-based studies demonstrate that smart design of packaging facilitates portion control. However, the extent to which consumers notice packaging features for portion control is not known. Therefore, this study investigated how individuals interact with food packaging, how they utilise the on-pack serving-size guidelines and how they make portion decisions. To do this, 25 adult participants were recruited to participate in an online semi-structured interview. Data were analysed using thematic analysis until saturation was achieved. Participants reported that they rarely attend to on-pack serving recommendations and indicated some resistance to them. Some structural features (small/single serving, pre-portioned and resealable packaging) were identified as facilitators of portion control. In contrast, the healthiness evaluation of the product from packaging cues was described as a permissive cue to eat more of the product. Participants in this study value their autonomy and control, preferring convenient behavioural choices over recommended portion servings. They also reported future concerns about the effects of their diet on health, but that current context (hunger, convenience) sometimes presented a barrier to healthy eating. Packaging does more than protect its contents, packaging can affect eating decisions to support portion control, and for some, offers permission to overconsume. This study identified ways that participants use packaging to make portion decisions, revealing the role of habits, current context and future health considerations. The interviews revealed the importance of consumer values on food choice in general and portion control in particular. In conclusion, smart food packaging design could use these findings to nudge healthy portion decisions by incorporating consumer values and by recognising consumer needs for habitual, current and future concerns.

A cohort study of 19 patients with gyrate atrophy of the choroid and retina (GACR).

PURPOSE: Gyrate atrophy of the choroid and retina (GACR) is an autosomal recessive inherited metabolic disorder (IMD) characterised by progressive retinal degeneration, leading to severe visual impairment. The rapid developments in ophthalmic genetic therapies warrant knowledge on clinical phenotype of eligible diseases such as GACR to define future therapeutic parameters in clinical trials. METHODS: Retrospective chart analysis was performed in nineteen patients. Data were analysed using IBM SPSS Statistics version 28.0.1.1. RESULTS: Nineteen patients were included with a mean age of 32.6 years (range 8-58). Mean age at onset of ophthalmic symptoms was 7.9 years (range 3-16). Median logMAR of visual acuity at inclusion was 0.26 (range -0.18-3.00). Mean age at cataract surgery was 28.8 years (n = 11 patients). Mean spherical equivalent of the refractive error was -8.96 (range -20.87 to -2.25). Cystoid maculopathy was present in 68% of patients, with a loss of integrity of the foveal ellipsoid zone (EZ) in 24/38 eyes. Of the 14 patients treated with dietary protein restriction, the four patients who started the diet before age 10 showed most benefit. CONCLUSION: This study demonstrates the severe ophthalmic disease course associated with GACR, as well as possible benefit of early dietary treatment. In addition to visual loss, patients experience severe myopia, early-onset cataract, and CME. There is a loss of foveal EZ integrity at a young age, emphasising the need for early diagnosis enabling current and future therapeutic interventions.

Biomarker-based text messages to promote lactation success in mothers of critically Ill infants: a randomized controlled pilot study.

OBJECTIVE: Infrequent breast pumping limits mother's own milk production in mothers of infants admitted to the neonatal intensive care unit. We aimed to determine the feasibility and benefit of biomarker-based personalized text messages on pumping frequency and milk sodium levels. A secondary aim examined lactation outcomes. STUDY DESIGN: In this randomized controlled pilot study, 51 mothers were randomized to receive personalized text messages regarding pumping frequency or standard care. RESULTS: There were no differences in pumped milk volume or sodium level, however, there was a trend towards the intervention group pumping more frequently, which was significant on day 5 (p = 0.035), and they lactated nearly 9 days longer. Post-hoc analysis found the intervention group tended to be more likely to pump ≥ 500 mL by day14 (p = 0.08), a marker of long-term lactation success. CONCLUSION: Personalized biomarker-based text messages are feasible and may support lactation in mothers of critically ill infants.

Navigating the outcome maze: a scoping review of outcomes and instruments in clinical trials in genetic neurodevelopmental disorders and intellectual disability.

Background: Individuals with genetic neurodevelopmental disorders (GNDs) or intellectual disability (ID) are often affected by complex neuropsychiatric comorbidities. Targeted treatments are increasingly available, but due to the heterogeneity of these patient populations, choosing a key outcome and corresponding outcome measurement instrument remains challenging. Objectives: The aim of this scoping review was to describe the research on outcomes and instruments used in clinical trials in GNDs and ID. Eligibility criteria: Clinical trials in individuals with GNDs and ID for any intervention over the past 10 years were included in the review. Sources of evidence: MEDLINE, PsycINFO, and Cochrane CENTRAL were searched. Titles and abstracts were independently screened for eligibility with a subsample of 10% double-screening for interrater reliability. Data from full texts were independently reviewed. Discrepancies were discussed until consensus was reached. Charting methods: Information was recorded on patient populations, interventions, designs, outcomes, measurement instruments, and type of reporter when applicable. Qualitative and descriptive analyses were performed. Results: We included 312 studies reporting 91 different outcomes, with cognitive function most frequently measured (28%). Various outcome measurement instruments (n = 457) were used, with 288 in only a single clinical trial. There were 18 genetic condition-specific instruments and 16 measures were designed ad-hoc for one particular trial. Types of report included proxy-report (39%), self-report (22%), clinician-report (16%), observer-report (6%), self-assisted report (1%), or unknown (16%). Conclusion: This scoping review of current practice reveals a myriad of outcomes and outcome measurement instruments for clinical trials in GNDs and ID. This complicates generalization, evidence synthesis, and evaluation. It underlines the need for consensus on suitability, validity, and relevancy of instruments, ultimately resulting in a core outcome set. A series of steps is proposed to move from the myriad of measures to a more unified approach.

Navigating the maze of outcome measures in rare disorders Treatments for genetic neurodevelopmental disorders and intellectual disability are increasingly available. However, it is hard to find appropriate instruments to measure whether these treatments are working. This hampers research and means some patients might not get the treatment they need. This scoping review provides an overview of investigated outcomes in this group, and with which instruments these are measured. It reveals that many different and overlapping outcomes are measured, complicating gathering, combining, and comparing of evidence. This scoping review underlines the need for harmonization and consensus on suitability, validity, and relevancy. Steps are proposed to move from the maze of outcome measures to a unified approach. Also, we provided recommendations for researchers to measure what matters to affected individuals and patient-centered care.

Corrigendum to "Effectiveness of L-serine supplementation in children with a GRIN2B loss-of-function mutation: Rationale and protocol for single patient (n-of-1) multiple cross-over trials" [Contemp. Clin. Trials Commun. 36 (2023)/ DOI: 10.1016/j.conctc.2023.101233].

[This corrects the article DOI: 10.1016/j.conctc.2023.101233.].

Accuracy of heart failure ascertainment using routinely collected healthcare data: a systematic review and meta-analysis.

BACKGROUND: Ascertainment of heart failure (HF) hospitalizations in cardiovascular trials is costly and complex, involving processes that could be streamlined by using routinely collected healthcare data (RCD). The utility of coded RCD for HF outcome ascertainment in randomized trials requires assessment. We systematically reviewed studies assessing RCD-based HF outcome ascertainment against "gold standard" (GS) methods to study the feasibility of using such methods in clinical trials. METHODS: Studies assessing International Classification of Disease (ICD) coded RCD-based HF outcome ascertainment against GS methods and reporting at least one agreement statistic were identified by searching MEDLINE and Embase from inception to May 2021. Data on study characteristics, details of RCD and GS data sources and definitions, and test statistics were reviewed. Summary sensitivities and specificities for studies ascertaining acute and prevalent HF were estimated using a bivariate random effects meta-analysis. Heterogeneity was evaluated using I2 statistics and hierarchical summary receiver operating characteristic (HSROC) curves. RESULTS: A total of 58 studies of 48,643 GS-adjudicated HF events were included in this review. Strategies used to improve case identification included the use of broader coding definitions, combining multiple data sources, and using machine learning algorithms to search free text data, but these methods were not always successful and at times reduced specificity in individual studies. Meta-analysis of 17 acute HF studies showed that RCD algorithms have high specificity (96.2%, 95% confidence interval [CI] 91.5-98.3), but lacked sensitivity (63.5%, 95% CI 51.3-74.1) with similar results for 21 prevalent HF studies. There was considerable heterogeneity between studies. CONCLUSIONS: RCD can correctly identify HF outcomes but may miss approximately one-third of events. Methods used to improve case identification should also focus on minimizing false positives.

"I see it very much as an end-of-life food" - Barriers to oral nutritional supplement adherence, views from healthy older adults.

Malnutrition affects approximately one quarter of UK adults aged 65 years and over. As the global demographic shift continues, malnutrition is expected to increase. Oral nutritional supplements (ONS) are used both to prevent and to treat malnutrition. However, their effectiveness is compromised by poor adherence, and it is not well understood what contributes to this. Therefore, the current research was designed to explore ONS adherence from the parallel perspectives of ONS as a prescribed "medication" and as a food supplement/substitute. Eighteen older adults (13F, 5M; mean age = 73.4 yr; range: 70-80 yr) participated in focus groups (three in-person and one online), to investigate experiences of taking prescribed medications, including dietary supplements, and what should be factors to consider in supporting regular intake of ONS for trial development, as well as any potential improvements to products. Focus group sessions were recorded and then transcribed. Thematic Analysis was applied to the transcripts by the first author, and themes were discussed in depth, using exemplar quotes from participants. Five dominant themes were identified from the data: Disgust, Palatability and Acceptance; End-of-Life Care; Resistance to Medicines; Rituals and Reminders; and Real Food Displacement. Nutritional supplements were characterised as "disgusting", "manufactured", and associated with serious, chronic illness, as well as end-of-life care, in contrast to probiotics which were linked with health and wellness. The sweet taste of ONS was identified as a barrier to intake, given that it is generally associated with a signal to stop eating, and low hunger. As a group, participants tried to "avoid taking medicines", and viewed the need to have them negatively, yet most regularly took prescribed medication and/or vitamin supplements. Participants identified several, rituals and reminders to take medicines, including meal-based, or time-of-day-based prompts (e.g., before, with or after meals). To improve adherence, savoury products were suggested, as well as a more person-centred approach to individual nutritional needs and preferences. Overall, the group discussion mainly identified barriers to intake, but that improving taste, adding to "real food" (not replacing meals), and offering variety of flavour and form (e.g., savoury soups as well as sweet drinks) could be included in future trials to improve appeal and therefore intake. Future work should continue to explore how best to formulate, market and/or prescribe ONS, and how this might vary for malnutrition prevention vs treatment strategies.

Platelet proteomic profiling in sitosterolemia suggests thrombocytopenia is driven by lipid disorder and not platelet aberrations.

ABSTRACT: Sitosterolemia is a rare autosomal recessive genetic disorder in which patients develop hypercholesterolemia and may exhibit abnormal hematologic and/or liver test results. In this disease, dysfunction of either ABCG5 or ABCG8 results in the intestinal hyperabsorption of all sterols, including cholesterol and, more specifically, plant sterols or xenosterols, as well as in the impaired ability to excrete xenosterols into the bile. It remains unknown how and why some patients develop hematologic abnormalities. Only a few unrelated patients with hematologic abnormalities at the time of diagnosis have been reported. Here, we report on 2 unrelated pedigrees who were believed to have chronic immune thrombocytopenia as their most prominent feature. Both consanguineous families showed recessive gene variants in ABCG5, which were associated with the disease by in silico protein structure analysis and clinical segregation. Hepatosplenomegaly was absent. Thrombopoietin levels and megakaryocyte numbers in the bone marrow were normal. Metabolic analysis confirmed the presence of strongly elevated plasma levels of xenosterols. Potential platelet proteomic aberrations were longitudinally assessed following dietary restrictions combined with administration of the sterol absorption inhibitor ezetimibe. No significant effects on platelet protein content before and after the onset of treatment were demonstrated. Although we cannot exclude that lipotoxicity has a direct and platelet-specific impact in patients with sitosterolemia, our data suggest that thrombocytopenia is neither caused by a lack of megakaryocytes nor driven by proteomic aberrations in the platelets themselves.

The impact of school-based cooking classes on vegetable intake, cooking skills and food literacy of children aged 4-12 years: A systematic review of the evidence 2001-2021.

BACKGROUND: Many children consume a poor quality diet with only a third of children aged 6-9 years eating vegetables daily. A high quality diet is important for good health in childhood; however, the prevalence of children living with obesity has doubled from 10% to 23% during primary school in the UK. Cooking lessons have the potential to improve diet quality and reduce obesity prevalence in childhood, both of which are associated with improved cardiometabolic outcomes in adulthood. The aim of this systematic review is to investigate the impact of school-based cooking classes on cooking skills, food literacy and vegetable intake of children aged 4-12 years. METHODS: We conducted a systematic review of OVID Medline, OVID Embase, EBSCO CINHAL and EBSCO ERIC for comparative studies that evaluated outcomes of children receiving cooking classes compared to a control group. Interventions included contained food preparation or a cooking activities and took place on school premises. Risk of bias was assessed using ROB2 and Robins-I. Outcomes were pooled in a meta-analysis using a random-effects model using standardised mean differences or reviewed using narrative synthesis. Certainty of evidence was assessed using GRADE. RESULTS: We included 21 studies, (6 randomised). Meta-analysis showed a small positive effect on cooking self-efficacy of 0.39 units (95% CI 0.05 to 0.54), and a small positive effect on vegetable intake of 0.25 units (95% CI 0.05 to 0.45). Programmes with more than 6 h of cooking showed the greatest effects. CONCLUSIONS: Children's cooking programmes result in small improvements in cooking efficacy and vegetable intake, particularly those with more than 6 h of classes. It is recommended that future interventions use consistent measurement for children's food literacy and cooking confidence.

Breaking the chains of lipoprotein lipase deficiency: A pediatric perspective on the efficacy and safety of Volanesorsen.

RATIONALE: Lipoprotein lipase (LPL) deficiency, a rare inherited metabolic disorder, is characterized by high triglyceride (TG) levels and life-threatening acute pancreatitis. Current treatment for pediatric patients involves a lifelong severely fat-restricted diet, posing adherence challenges. Volanesorsen, an EMA-approved RNA therapy for adults, effectively reduces TG levels by decreasing the production of apolipoprotein C-III. This 96-week observational open-label study explores Volanesorsen's safety and efficacy in a 13-year-old female with LPL deficiency. METHODS: The patient, with a history of severe TG elevations, 53 hospital admissions, and life-threatening recurrent pancreatitis despite dietary restrictions, received weekly subcutaneous Volanesorsen injections. We designed a protocol for this investigator-initiated study, primarily focusing on changes in fasting TG levels and hospital admissions. RESULTS: While the injections caused occasional pain and swelling, no other adverse events were observed. TG levels decreased during treatment, with more measurements below the pancreatitis risk threshold compared to pre-treatment. No hospital admissions occurred in the initial 14 months of treatment, contrasting with 21 admissions in the 96 weeks before. In the past 10 months, two pancreatitis episodes may have been linked to dietary noncompliance. Dietary restrictions were relaxed, increasing fat intake by 65% compared to baseline. While not fully reflected in the PedsQL, both parents and the patient narratively reported an improved quality of life. CONCLUSION: This study demonstrates, for the first time, that Volanesorsen is tolerated in a pediatric patient with severe LPL deficiency and effectively lowers TG levels, preventing life-threatening complications. This warrants consideration for expanded access in this population.

Vision on gyrate atrophy: why treat the eye?

In the April issue of this Journal, Boffa and coworkers put forward a new therapeutic approach for Gyrate Atrophy of the Choroid and Retina (GACR; OMIM 258870) (Boffa et al, 2023). The authors propose to apply gene therapy to the liver for GACR, a metabolic disease primarily affecting eyesight due to retinal degeneration. Their vision is enthusiastically supported by a News and Views comment in the same issue (Seker Yilmaz and Gissen, 2023). However, based on disease pathology, patient's needs, ethical considerations, therapeutic developmental time lines, and current state of the art of gene therapy for liver and eye, we have a different view on this issue: We argue below that local treatment of the eye is the preferred option for GACR.

Biological aging markers in blood and brain tissue indicate age acceleration in alcohol use disorder.

BACKGROUND: Alcohol use disorder (AUD) is associated with increased mortality and morbidity risk. A reason for this could be accelerated biological aging, which is strongly influenced by disease processes such as inflammation. As recent studies of AUD show changes in DNA methylation and gene expression in neuroinflammation-related pathways in the brain, biological aging represents a potentially important construct for understanding the adverse effects of substance use disorders. Epigenetic clocks have shown accelerated aging in blood samples from individuals with AUD. However, no systematic evaluation of biological age measures in AUD across different tissues and brain regions has been undertaken. METHODS: As markers of biological aging (BioAge markers), we assessed Levine's and Horvath's epigenetic clocks, DNA methylation telomere length (DNAmTL), telomere length (TL), and mitochondrial DNA copy number (mtDNAcn) in postmortem brain samples from Brodmann Area 9 (BA9), caudate nucleus, and ventral striatum (N = 63-94), and in whole blood samples (N = 179) of individuals with and without AUD. To evaluate the association between AUD status and BioAge markers, we performed linear regression analyses while adjusting for covariates. RESULTS: The majority of BioAge markers were significantly associated with chronological age in all samples. Levine's epigenetic clock and DNAmTL were indicative of accelerated biological aging in AUD in BA9 and whole blood samples, while Horvath's showed the opposite effect in BA9. No significant association of AUD with TL and mtDNAcn was detected. Measured TL and DNAmTL showed only small correlations in blood and none in brain. CONCLUSIONS: The present study is the first to simultaneously investigate epigenetic clocks, telomere length, and mtDNAcn in postmortem brain and whole blood samples in individuals with AUD. We found evidence for accelerated biological aging in AUD in blood and brain, as measured by Levine's epigenetic clock, and DNAmTL. Additional studies of different tissues from the same individuals are needed to draw valid conclusions about the congruence of biological aging in blood and brain.

Milk Biomarkers of Secretory Activation in Breast Pump-Dependent Mothers of Preterm Infants: An Integrative Review.

Background: Lack of mother's own milk (MOM) at discharge from the neonatal intensive care unit (NICU) is a global problem and is often attributable to inadequate MOM volume. Evidence suggests that the origins of this problem are during the first 14 days postpartum, a time period that includes secretory activation (SA; lactogenesis II, milk coming in). Objectives: To describe and summarize evidence regarding use of MOM biomarkers (MBMs) as a measure of SA in pump-dependent mothers of preterm infants in the NICU and to identify knowledge gaps requiring further investigation. Methods: An integrative review was conducted using Whittemore and Knafl methodology incorporating the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. A search using electronic databases MEDLINE (through PubMed) and CINAHL (Cumulative Index to Nursing and Allied Health Literature) and reference lists of included articles was conducted. Results: Of the 40 articles retrieved, 6 met the criteria for inclusion. Results revealed the following five findings: (1) Achievement of SA defined by MBMs is delayed and/or impaired in mothers of preterm infants. (2) MBMs are associated with pumped MOM volume. (3) Achievement of SA defined by MBMs is associated with pumping frequency. (4) Delayed and/or impaired achievement of SA defined by MBMs may be exacerbated by maternal comorbidities. (5) There is a lack of consensus as to which MBM(s) and analysis techniques should be used in research and practice. Conclusions: MBMs hold tremendous potential to document and monitor achievement of SA in mothers of preterm infants, with multiple implications for research and clinical practice.

Impact of physical activity on disability-free and disabled life expectancies in middle-aged and older adults: Data from the healthy aging longitudinal study in Taiwan.

AIM: Leisure-time physical activity (LTPA) promotes healthy aging; however, data on work-related physical activity (WPA) are inconsistent. This study was conducted to examine the disability-free life expectancy (DFLE) and disabled life expectancy (DLE) across physical activity levels, with a focus on WPA, in middle-aged and older adults. METHODS: Data from 5663 community-dwelling participants aged ≥55 years and enrolled in the Healthy Aging Longitudinal Study in Taiwan were evaluated. Energy expenditures from LTPA and WPA were calculated from baseline questionnaires and categorized into sex-specific cutoffs. Disability was based on repeat measures of participants' activities of daily living and instrumental activities of daily living. Mortality was confirmed via data linkage with the Death Certificate database. DFLE and DLE were estimated from discrete-time multistate life-table models. RESULTS: At age 65, women with low WPA had a DLE of 2.88 years (95% confidence interval [CI], 1.67-4.08), which was shorter than that of women without WPA (DLE, 5.24 years; 95% CI, 4.65-5.83) and with high WPA (DLE, 4.01 years; 95% CI, 2.69-5.34). DFLE and DLE were similar across WPA levels in men. DFLE tended to increase as the LTPA increased in men and women. CONCLUSION: Women with low WPA had shorter DLE than did those with no or high WPA. To reduce the risks of disability associated with physical activity, public policy should advocate for older people to watch the type, amount, and intensity of their activities as these may go ignored during WPA. Geriatr Gerontol Int 2024; 24: 229-239.

Appetitive traits from childhood to adolescence: Analysis of their stability, derivation of trajectory profiles, and associated characteristics.

This study aimed to assess the potential stability of appetitive traits from childhood to early adolescence, identify groups of individuals with distinct trajectories for these traits, and explore their association with other child and family characteristics. Participants were 5040 children from the Generation XXI cohort. Appetitive traits were assessed with the Children's Eating Behaviour Questionnaire (CEBQ) at ages seven, 10, and 13 (eight subscales). Mixed-effect models estimated individual trajectories of appetitive traits and Gaussian mixture models identified groups following different trajectories (appetitive trait trajectory profiles). Appetitive traits showed moderate-to-high stability across the three ages (intra-class correlation coefficients:0.66-0.83); most of the variance observed across time were due to persistent individual differences rather than age-related changes. Six appetitive trait trajectory profiles were identified: 'Moderate appetite' (scores close to the average) (29% of children), 'Small to moderate appetite' (lowest food approach and emotional eating) (26%), 'Increasing appetite' (increasing food approach) (15%), 'Avid appetite' (highest food approach and lowest food avoidance) (12%), 'Smallest appetite' (highest food avoidance and low food approach) (10%), and 'Small appetite but increasing' (decreasing high food avoidance and Desire to Drink) (8%). In multinomial logistic regression, these profiles were associated with different child and family characteristics. Compared to children with a 'Moderate appetite' profile, those with higher BMI, who desired a thinner body, whose mothers were younger, had lower education, higher pre-pregnancy BMI (OR = 1.07; 95%CI:1.04,1.09), smoked during pregnancy (OR = 1.51; 95%CI:1.21,1.90), and used more restrictive feeding practices (OR = 1.79; 95%CI:1.57,2.03) had increased odds of belonging to the 'Avid Appetite'. In conclusion, distinct appetitive trait trajectory profiles emerged, differentiating individuals with avid and small appetites. These findings have implications for identifying children at higher risk for obesogenic profiles.

Comparing the Performance of Multiple Small-Data Personalized Tacrolimus Dosing Models for Pediatric Liver Transplant: A Retrospective Study.

Tacrolimus is a potent immunosuppressant used after pediatric liver transplant. However, tacrolimus's narrow therapeutic window, reliance on physicians' experience for the dose titration, and intra- and inter-patient variability result in liver transplant patients falling out of the target tacrolimus trough levels frequently. Existing personalized dosing models based on the area-under-the-concentration over time curves require a higher frequency of blood draws than the current standard of care and may not be practically feasible. We present a small-data artificial intelligence-derived platform, CURATE.AI, that uses data from individual patients obtained once daily to model the dose and response relationship and identify suitable doses dynamically. Retrospective optimization using 6 models of CURATE.AI and data from 16 patients demonstrated good predictive performance and identified a suitable model for further investigations.Clinical Relevance- This study established and compared the predictive performance of 6 personalized tacrolimus dosing models for pediatric liver transplant patients and identified a suitable model with consistently good predictive performance based on data from pediatric liver transplant patients.

Effectiveness of L-serine supplementation in children with a GRIN2B loss-of-function mutation: Rationale and protocol for single patient (n-of-1) multiple cross-over trials.

Rationale: Loss-of-function (LoF) mutations in GRIN2B result in neurologic abnormalities due to N-methyl-D-aspartate receptor (NMDAR) dysfunction. Affected persons present with various symptoms, including intellectual developmental disability (IDD), hypotonia, communication deficits, motor impairment, complex behavior, seizures, sleep disorders and gastrointestinal disturbance. Recently, in vitro experiments showed that D-serine mitigates function to GluN2B (mutation)-containing NMDARs. 11 previous case reports are published on (experimental) L-serine treatment of patients between 1.5 and 12 years old with GRIN2B missense or null mutations, some of whom showed notable improvement in motor and cognitive performance, communication, behavior and abnormalities on electro encephalography (EEG). Our objective is to further evaluate the effectiveness of L-serine for GRIN2B-related neurodevelopmental disorder (GRIN2B-NDD), using an n-of-1 trial design, increasing the level of evidence. Methods/design: These n-of-1 trials, consisting of 2 cycles of 6 months, will be performed to evaluate the effect of L-serine compared to placebo in 4 patients with a GRIN2B LoF mutation. The aggregation of multiple n-of-1 trials will provide an estimate of the average treatment effects.The primary outcome is the Perceive-Recall-Plan-Perform of Task Analysis, assessing developmental skills. Secondary outcomes include Goal Attainment Scaling, seizure log books, EEGs, sleep log books, the irritability subscale of the Aberrant Behavior Checklist, the Bristol Stool Scale and the Pediatric Quality of Life Inventory. Conclusion: This study employs an innovative methodological approach to evaluate the effectiveness of L-serine for patients with a GRIN2B LoF mutation. The results will establish a foundation for implementing L-serine as a disease-modifying treatment in GRIN2B-NDD.

A Delphi Survey Study to Formulate Statements on the Treatability of Inherited Metabolic Disorders to Decide on Eligibility for Newborn Screening.

The Wilson and Jungner (W&J) and Andermann criteria are meant to help select diseases eligible for population-based screening. With the introduction of next-generation sequencing (NGS) methods for newborn screening (NBS), more inherited metabolic diseases (IMDs) can technically be included, and a revision of the criteria was attempted. This study aimed to formulate statements and investigate whether those statements could elaborate on the criterion of treatability for IMDs to decide on eligibility for NBS. An online Delphi study was started among a panel of Dutch IMD experts (EPs). EPs evaluated, amended, and approved statements on treatability that were subsequently applied to 10 IMDs. After two rounds of Delphi, consensus was reached on 10 statements. Application of these statements selected 5 out of 10 IMDs proposed for this study as eligible for NBS, including 3 IMDs in the current Dutch NBS. The statement: 'The expected benefit/burden ratio of early treatment is positive and results in a significant health outcome' contributed most to decision-making. Our Delphi study resulted in 10 statements that can help to decide on eligibility for inclusion in NBS based on treatability, also showing that other criteria could be handled in a comparable way. Validation of the statements is required before these can be applied as guidance to authorities.

A Scoping Review of the Oral Microbiome in Preterm Infants.

The purpose of this scoping review was to examine the oral microbiome composition in preterm infants, sampling and collection methods, as well as exposures associated with oral microbiome composition and health implications. We conducted a scoping review of the literature using the Arskey and O'Malley framework. We identified a total of 13 articles which met our inclusion criteria and purpose of this scoping review. Articles included in this review compared the oral microbiome in preterm infants to term infants, examined alterations to the oral microbiome over time, compared the oral microbiome to different body site microbiomes, and explored associations with clinically relevant covariates and outcomes. Exposures associated with the diversity and composition of the oral microbiome in preterm infants included delivery mode, oral feeding, oropharyngeal care, skin-to-skin care, and antibiotics. Day of life and birth weight were also associated with oral microbiome composition. The oral microbiome may be associated with the composition of the tracheal and gut microbiomes, likely due to their proximity. Alpha and beta diversity findings varied across studies as well as the relative abundance of taxa. This is likely due to the different sampling techniques and timing of collection, as well as the wide range of infant clinical characteristics. Multiple factors may influence the composition of the oral microbiome in preterm infants. However, given the heterogeneity of sampling techniques and results within this review, the evidence is not conclusive on the development as well as short- and long-term implications of the oral microbiome in preterm infants and needs to be explored in future research studies. KEY POINTS: · Day of life is a critical factor in oral microbiome development in preterm infants.. · The oral microbiome may be associated with tracheal and gut microbiome colonization.. · Future research should examine sampling methodology for examining the oral microbiome.. · Future research should explore associations with the oral microbiome and adverse health outcomes..