Individualized prediction models in ADHD: a systematic review and meta-regression.

There have been increasing efforts to develop prediction models supporting personalised detection, prediction, or treatment of ADHD. We overviewed the current status of prediction science in ADHD by: (1) systematically reviewing and appraising available prediction models; (2) quantitatively assessing factors impacting the performance of published models. We did a PRISMA/CHARMS/TRIPOD-compliant systematic review (PROSPERO: CRD42023387502), searching, until 20/12/2023, studies reporting internally and/or externally validated diagnostic/prognostic/treatment-response prediction models in ADHD. Using meta-regressions, we explored the impact of factors affecting the area under the curve (AUC) of the models. We assessed the study risk of bias with the Prediction Model Risk of Bias Assessment Tool (PROBAST). From 7764 identified records, 100 prediction models were included (88% diagnostic, 5% prognostic, and 7% treatment-response). Of these, 96% and 7% were internally and externally validated, respectively. None was implemented in clinical practice. Only 8% of the models were deemed at low risk of bias; 67% were considered at high risk of bias. Clinical, neuroimaging, and cognitive predictors were used in 35%, 31%, and 27% of the studies, respectively. The performance of ADHD prediction models was increased in those models including, compared to those models not including, clinical predictors (ß = 6.54, p = 0.007). Type of validation, age range, type of model, number of predictors, study quality, and other type of predictors did not alter the AUC. Several prediction models have been developed to support the diagnosis of ADHD. However, efforts to predict outcomes or treatment response have been limited, and none of the available models is ready for implementation into clinical practice. The use of clinical predictors, which may be combined with other type of predictors, seems to improve the performance of the models. A new generation of research should address these gaps by conducting high quality, replicable, and externally validated models, followed by implementation research.

Maximal sustainable energy intake during transatlantic ocean rowing is insufficient for total energy expenditure and skeletal muscle mass maintenance.

Studies of extreme endurance have suggested that there is an alimentary limit to energy intake (EI) of ∼2.5 × resting metabolic rate (RMR). To gain further insight, this study aimed to simultaneously measure EI, total energy expenditure (TEE) body mass and muscle mass in a large cohort of males and females of varying ages during a transatlantic rowing race. Forty-nine competitors (m = 32, f = 17; age 24-67 years; time at sea 46 ± 7 days) in the 2020 and 2021 Talisker Whisky Atlantic Challenge rowed 12-18 hday-1 for ∼3000 miles. TEE was assessed in the final week of the row using 2 H2 18 O doubly labelled water, and EI was analysed from daily ration packs over this period. Thickness of relatively active (vastus lateralis, intermedius, biceps brachaii and rectus abdominus) and inactive (gastrocnemius, soleus and triceps) muscles was measured pre (<7 days) and post (<24 h) row using ultrasound. Body mass was measured and used to calculate RMR from standard equations. There were no sex differences in males and females in EI (2.5 ± 0.5 and 2.3 ± 0.4 × RMR, respectively, P = 0.3050), TEE (2.5 ± 1.0 and 2.3 ± 0.4 × RMR, respectively, P = 0.5170), or body mass loss (10.2 ± 3.1% and 10.0 ± 3.0%, respectively, P = 0.8520), and no effect of age on EI (P = 0.5450) or TEE (P = 0.9344). Muscle loss occurred exclusively in the calf (15.7% ± 11.4% P < 0.0001), whilst other muscles remained unchanged. After 46 days of prolonged ultra-endurance ocean rowing incurring 10% body mass loss, maximal sustainable EI of ∼2.5 × RMR was unable to meet total TEE suggesting that there is indeed a physiological capacity to EI.

The evolution of nutritional care in children and young people with acute lymphoblastic leukaemia: a narrative review.

BACKGROUND: Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy in the world. Advances in treatment protocols have resulted in survival rates of >80% in most high-income countries (HIC); however, children and young people (CYP) with ALL continue to face significant nutrition-related challenges during treatment. METHODS: This narrative review outlines the changing landscape of treatment and survivorship for CYP with ALL and the advances in nutrition knowledge that call for changes to clinical nutrition practice. RESULTS: The incidence of ALL has remained stable in HIC; however, there have been significant advances in survival over the past 30 years. Overweight and obesity are increasingly prevalent in CYP with ALL at diagnosis, during treatment and in survivorship. Coupled with poor diet quality, high-energy and saturated fat intakes, altered eating behaviours and inactivity, this necessitates the need for a shift in nutrition intervention. Undernutrition remains a concern for CYP with high-risk treatment protocols where oral or enteral nutrition support remains a cornerstone of maintaining nutrition status. CONCLUSIONS: With improved treatment protocols and high survival rates, a shift to focusing on diet quality, prevention of excessive weight gain and obesity during treatment and survivorship is necessary.

Optimizing the Prediction of Depression Remission: A Longitudinal Machine Learning Approach.

Decisions about when to change antidepressant treatment are complex and benefit from accurate prediction of treatment outcome. Prognostic accuracy can be enhanced by incorporating repeated assessments of symptom severity collected during treatment. Participants (n = 714) from the Genome-Based Therapeutic Drugs for Depression study received escitalopram or nortriptyline over 12 weeks. Remission was defined as scoring ≤ 7 on the Hamilton Rating Scale. Predictors included demographic, clinical, and genetic variables (at 0 weeks) and measures of symptom severity (at 0, 2, 4, and 6 weeks). Longitudinal descriptors extracted with growth curves and topological data analysis were used to inform prediction of remission. Repeated assessments produced gradual and drug-specific improvements in predictive performance. By Week 4, models' discrimination in all samples reached levels that might usefully inform treatment decisions (area under the receiver operating curve (AUC) = 0.777 for nortriptyline; AUC = 0.807 for escitalopram; AUC = 0.794 for combined sample). Decisions around switching or modifying treatments for depression can be informed by repeated symptom assessments collected during treatment, but not until 4 weeks after the start of treatment.

A shortened surface electromyography recording is sufficient to facilitate home fasciculation assessment.

INTRODUCTION/AIMS: Fasciculations are an early clinical hallmark of amyotrophic lateral sclerosis (ALS), amenable to detection by high-density surface electromyography (HDSEMG). In conjunction with the Surface Potential Quantification Engine (SPiQE), HDSEMG offers improved spatial resolution for the analysis of fasciculations. This study aims to establish an optimal recording duration to enable longitudinal remote monitoring in the home. METHODS: Twenty patients with ALS and five patients with benign fasciculation syndrome (BFS) underwent serial 30 min HDSEMG recordings from biceps brachii and gastrocnemii. SPiQE was independently applied to abbreviated epochs within each 30-min recording (0-5, 0-10, 0-15, 0-20, and 0-25 min), outputting fasciculation frequency, amplitude median and amplitude interquartile range. Bland-Altman plots and intraclass correlation coefficients (ICC) were used to assess agreement with the validated 30-min recording. RESULTS: In total, 506 full recordings were included. The 5 min recordings demonstrated diverse and relatively poor agreement with the 30 min baselines across all parameters, muscles and patient groups (ICC = 0.32-0.86). The 15-min recordings provided more acceptable and stable agreement (ICC = 0.78-0.98), which did not substantially improve in longer recordings. DISCUSSION: For the detection and quantification of fasciculations in patients with ALS and BFS, HDSEMG recordings can be halved from 30 to 15 min without significantly compromising the primary outputs. Reliance on a shorter recording duration should lead to improved tolerability and repeatability among patients, facilitating longitudinal remote monitoring in patients' homes.

The impact of plasma 25-hydroxyvitamin D on pulmonary function and exercise physiology in cystic fibrosis: A multicentre retrospective study.

BACKGROUND: A 25-hydroxyvitamin D (25OHD) may exert immunomodulatory effects on respiratory health, which may translate to improvements in exercise physiology. Thus, we aimed to investigate whether plasma 25OHD is associated with lung function and aerobic fitness in people with cystic fibrosis (pwCF). METHODS: A multicentre retrospective review of pwCF (> 9 years old) attending the Royal Hospital for Sick Children (Edinburgh) or Wessex CF-Unit (Southampton) was performed between July 2017 and October 2019. Demographic and clinical data were collected. Plasma 25OHD measured closest in time to clinical cardiopulmonary exercise testing and/or spirometry [forced expiratory volume (FEV1 )% predicted] was recorded. Pancreatic insufficiency was diagnosed based on faecal elastase of < 100 µg g-1 . We performed multiple-regression analysis with aerobic fitness outcomes [peak oxygen uptake (VO2 peak )] and FEV1 % predicted as primary outcomes. RESULTS: Ninety pwCF [mean ± SD age: 19.1 ± 8.6 years, 54 (60%) children, 48 (53%) males and 88 (98%) Caucasian] were included. 25OHD deficiency and insufficiency was 15 (17%) and 44 (49%), respectively. 25OHD deficiency and insufficiency was significantly associated with pancreatic insufficiency (χ2  = 4.8, p = 0.02). Plasma 25OHD was not significantly associated with FEV1 % predicted (r2  = 0.06, p = 0.42, 95% CI = -0.09 to 0.19) or VO2 peak (r2  = 0.04, p = 0.07, 95% CI = -011 to 0.005) in all pwCF. However, 25OHD was significantly associated with both FEV1 % (r2  = 0.15, p = 0.02, 95% CI = 1.99-2.64) and VO2 peak (r2  = 0.13, p = 0.05, 95% CI = -0.26 to -0.005) in the paediatric cohort. CONCLUSIONS: We showed that 25OHD is associated with improved lung function and aerobic fitness in children and adolescents with CF. Mechanistic and high-quality prospective studies including both lung function and aerobic fitness as primary outcomes are now warranted.

Identifying homogeneous subgroups of patients and important features: a topological machine learning approach.

BACKGROUND: This paper exploits recent developments in topological data analysis to present a pipeline for clustering based on Mapper, an algorithm that reduces complex data into a one-dimensional graph. RESULTS: We present a pipeline to identify and summarise clusters based on statistically significant topological features from a point cloud using Mapper. CONCLUSIONS: Key strengths of this pipeline include the integration of prior knowledge to inform the clustering process and the selection of optimal clusters; the use of the bootstrap to restrict the search to robust topological features; the use of machine learning to inspect clusters; and the ability to incorporate mixed data types. Our pipeline can be downloaded under the GNU GPLv3 license at https://github.com/kcl-bhi/mapper-pipeline .

First-recruited motor units adopt a faster phenotype in amyotrophic lateral sclerosis.

KEY POINTS: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder of motor neurons, carrying a short survival. High-density motor unit recordings permit analysis of motor unit size (amplitude) and firing behaviour (afterhyperpolarization duration and muscle fibre conduction velocity). Serial recordings from biceps brachii indicated that motor units fired faster and with greater amplitude as disease progressed. First-recruited motor units in the latter stages of ALS developed characteristics akin to fast-twitch motor units, possibly as a compensatory mechanism for the selective loss of this motor unit subset. This process may become maladaptive, highlighting a novel therapeutic target to reduce motor unit vulnerability. ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with a median survival of 3 years. We employed serial high-density surface electromyography (HDSEMG) to characterize voluntary and ectopic patterns of motor unit (MU) firing at different stages of disease. By distinguishing MU subtypes with variable vulnerability to disease, we aimed to evaluate compensatory neuronal adaptations that accompany disease progression. Twenty patients with ALS and five patients with benign fasciculation syndrome (BFS) underwent 1-7 assessments each. HDSEMG measurements comprised 30 min of resting muscle and 1 min of light voluntary activity from biceps brachii bilaterally. MU decomposition was performed by the progressive FastICA peel-off technique. Inter-spike interval, firing pattern, MU potential area, afterhyperpolarization duration and muscle fibre conduction velocity were determined. In total, 373 MUs (ALS = 287; BFS = 86) were identified from 182 recordings. Weak ALS muscles demonstrated a lower mean inter-spike interval (82.7 ms) than strong ALS muscles (96.0 ms; P = 0.00919) and BFS muscles (95.3 ms; P = 0.0039). Mean MU potential area (area under the curve: 487.5 vs. 98.7 µV ms; P < 0.0001) and muscle fibre conduction velocity (6.2 vs. 5.1 m/s; P = 0.0292) were greater in weak ALS muscles than in BFS muscles. Purely fasciculating MUs had a greater mean MU potential area than MUs also under voluntary command (area under the curve: 679.6 vs. 232.4 µV ms; P = 0.00144). These results suggest that first-recruited MUs develop a faster phenotype in the latter stages of ALS, likely driven by the preferential loss of vulnerable fast-twitch MUs. Inhibition of this potentially maladaptive phenotypic drift may protect the longevity of the MU pool, stimulating a novel therapeutic avenue.

Fasciculation analysis reveals a novel parameter that correlates with predicted survival in amyotrophic lateral sclerosis.

INTRODUCTION: Prognostic uncertainty in amyotrophic lateral sclerosis (ALS) confounds clinical management planning, patient counseling, and trial stratification. Fasciculations are an early clinical hallmark of disease and can be quantified noninvasively. Using an innovative analytical method, we correlated novel fasciculation parameters with a predictive survival model. METHODS: Using high-density surface electromyography, we collected biceps recordings from ALS patients on their first research visit. By accessing an online survival prediction tool, we provided eight clinical and genetic parameters to estimate individual patient survival. Fasciculation analysis was performed using an automated algorithm (Surface Potential Quantification Engine), with a Cox proportional hazards model to calculate hazard ratios. RESULTS: The median predicted survival for 31 patients was 41 (interquartile range, 31.5-57) months. Univariate hazard ratios were 1.09 (95% confidence interval [CI], 1.03-1.16) for the rate of change of fasciculation frequency (RoCoFF) and 1.10 (95% CI, 1.01-1.19) for the amplitude dispersion rate. Only the RoCoFF remained significant (P = .04) in a multivariate model. DISCUSSION: Noninvasive measurement of fasciculations at a single time-point could enhance prognostic models in ALS, where higher RoCoFF values indicate shorter survival.

Genetic and Inflammatory Biomarkers Classify Small Intestine Inflammation in Asymptomatic First-degree Relatives of Patients With Crohn's Disease.

BACKGROUND & AIMS: Relatives of individuals with Crohn's disease (CD) carry CD-associated genetic variants and are often exposed to environmental factors that increase their risk for this disease. We aimed to estimate the utility of genotype, smoking status, family history, and biomarkers can calculate risk in asymptomatic first-degree relatives of patients with CD. METHODS: We recruited 480 healthy first-degree relatives (full siblings, offspring or parents) of patients with CD through the Guy's and St Thomas' NHS Foundation Trust and from members of Crohn's and Colitis, United Kingdom. DNA samples were genotyped using the Immunochip. We calculated a risk score for 454 participants, based on 72 genetic variants associated with CD, family history, and smoking history. Participants were assigned to highest and lowest risk score quartiles. We assessed pre-symptomatic inflammation by capsule endoscopy and measured 22 markers of inflammation in stool and serum samples (reference standard). Two machine-learning classifiers (elastic net and random forest) were used to assess the ability of the risk factors and biomarkers to identify participants with small intestinal inflammation in the same dataset. RESULTS: The machine-learning classifiers identified participants with pre-symptomatic intestinal inflammation: elastic net (area under the curve, 0.80; 95% CI, 0.62-0.98) and random forest (area under the curve, 0.87; 95% CI, 0.75-1.00). The elastic net method identified 3 variables that can be used to calculate odds for intestinal inflammation: combined family history of CD (odds ratio, 1.31), genetic risk score (odds ratio, 1.14), and fecal calprotectin (odds ratio, 1.04). These same 3 variables were among the 5 factors associated with intestinal inflammation in the random forest model. CONCLUSION: Using machine learning classifiers, we found that genetic variants associated with CD, family history, and fecal calprotectin together identify individuals with pre-symptomatic intestinal inflammation who are therefore at risk for CD. A tool for detecting people at risk for CD before they develop symptoms would help identify the individuals most likely to benefit from early intervention.

Fasciculations demonstrate daytime consistency in amyotrophic lateral sclerosis.

INTRODUCTION: Fasciculations represent early neuronal hyperexcitability in amyotrophic lateral sclerosis (ALS). To aid calibration as a disease biomarker, we set out to characterize the daytime variability of fasciculation firing. METHODS: Fasciculation awareness scores were compiled from 19 ALS patients. In addition, 10 ALS patients prospectively underwent high-density surface electromyographic (HDSEMG) recordings from biceps and gastrocnemius at three time-points during a single day. RESULTS: Daytime fasciculation awareness scores were low (mean: 0.28 muscle groups), demonstrating significant variability (coefficient of variation: 303%). Biceps HDSEMG recordings were highly consistent for fasciculation potential frequency (intraclass correlation coefficient [ICC] = 95%, n = 19) and the interquartile range of fasciculation potential amplitude (ICC = 95%, n = 19). These parameters exhibited robustness to observed fluctuations in data quality parameters. Gastrocnemius demonstrated more modest levels of consistency overall (44% to 62%, n = 20). DISCUSSION: There was remarkable daytime consistency of fasciculation firing in the biceps of ALS patients, despite sparse and intermittent awareness among patients' accounts.

Genetic variants in the promoter region of the calcium-sensing receptor gene are associated with its down-regulation in neuroblastic tumors.

We have previously reported that the calcium-sensing receptor (CaSR) is expressed in benign, differentiated neuroblastic tumors, and epigenetically silenced in undifferentiated, malignant cases. Furthermore, cinacalcet, an allosteric activator of the CaSR, reduces neuroblastoma tumor growth in preclinical models. However, to identify patients that might benefit from this treatment, a complete understanding of mechanisms governing CaSR expression in these tumors would be required. We have now analyzed two polymorphisms in the promoter region of the CASR gene (rs7652589 and rs1501899) by allelic discrimination in neuroblastoma patients and cell lines. Association of genotypes and haplotypes with CaSR mRNA levels and CASR promoter P2 methylation status was determined. Data presented show that minor alleles rs7652589 and rs1501899, present either in homo- or heterozygosis, were correlated with reduced CaSR mRNA levels in matching primary tumors and this association was independent of CASR promoter P2 hypermethylation. Haplotype AA was independently associated with reduced CaSR expression after adjusting by promoter P2 methylation status. These polymorphisms were identified in some ganglioneuromas in which CaSR expression is low despite exhibiting a high degree of differentiation. Furthermore, homozygous variants rs7652589 and rs1501899 were detected in SH-SY5Y cells, which are devoid of CaSR expression in the absence of hypermethylation of CASR promoter P2. In summary, minor alleles rs7652589 and rs1501899 are associated with reduced CaSR expression in neuroblastic tumors and neuroblastoma cell lines in which the CASR gene promoter P2 is not hypermethylated. Therefore, they potentially represent an additional mechanism of CASR transcriptional regulation in this group of developmental malignancies. © 2016 Wiley Periodicals, Inc.

5-Hydroxyvitamin D concentration in paediatric cancer patients from Scotland: a prospective cohort study.

Children with cancer are potentially at a high risk of plasma 25-hydroxyvitamin D (25(OH)D) inadequacy, and despite UK vitamin D supplementation guidelines their implementation remains inconsistent. Thus, we aimed to investigate 25(OH)D concentration and factors contributing to 25(OH)D inadequacy in paediatric cancer patients. A prospective cohort study of Scottish children aged 75 nmol/l). In all, eighty-two patients (median age 3·9, interquartile ranges (IQR) 1·9-8·8; 56 % males) and thirty-five controls (median age 6·2, IQR 4·8-9·1; 49 % males) were recruited. 25(OH)D inadequacy was highly prevalent in the controls (63 %; 22/35) and in the patients (64 %; 42/65) at both baseline and during treatment (33-50 %). Non-supplemented children had the highest prevalence of 25(OH)D inadequacy at every stage with 25(OH)D median ranging from 32·0 (IQR 21·0-46·5) to 45·0 (28·0-64·5) nmol/l. Older age at baseline (R -0·46; P<0·001), overnutrition (BMI≥85th centile) at 3 months (P=0·005; relative risk=3·1) and not being supplemented at 6 months (P=0·04; relative risk=4·3) may have contributed to lower plasma 25(OH)D. Paediatric cancer patients are not at a higher risk of 25(OH)D inadequacy than healthy children at diagnosis; however, prevalence of 25(OH)D inadequacy is still high and non-supplemented children have a higher risk. Appropriate monitoring and therapeutic supplementation should be implemented.

Adolescents and Dual Diagnosis in a Psychiatric Emergency Service. / Adolescentes y Diagnóstico Dual en el Servicio de Urgencias Psiquiátricas.

In recent years, both the prevalence of drug use and related child and adolescent psychiatric emergencies have risen sharply. There are few studies about the impact on child and adolescent emergency services. This study has a twofold aim. The first is to describe the prevalence of substance use disorders, mental disorders and dual diagnosis (substance use problems plus mental disorder) in adolescents in psychiatric emergency service. The second is to analyze clinical and healthcare differences between patients with dual diagnosis and patients with a mental disorder without substance use disorder.We retrospectively reviewed 4012 discharge forms for emergencies treated at the psychiatric emergency department during the period 2007-2009. We obtained a sample of 1795 visits. This sample was divided into two groups: the dual diagnosis group (n = 477) and the psychiatric disorder group (n = 1318).The dual diagnosis group accounted for 26.5% of psychiatric emergencies analyzed. Compared to the psychiatric disorder group,the dual diagnosis group had significantly more conduct disorders, social problems, involuntariness in the visit, less hospital admissions and less connection with the healthcare network.Adolescents with a dual diagnosis account for a high percentage of visits at child and adolescent psychiatric emergency services. This patient group requires specialized care both at emergency services and in specific units. Accordingly, these units should play a triple role when handling dual diagnosis: detection, brief treatment and referral to a specialised unit.

En los últimos años, la prevalencia del consumo de drogas y las urgencias psiquiátricas relacionadas han incrementado notablemente en los adolescentes. Pocos estudios han examinado el impacto en los servicios de urgencias psiquiátricos infantojuveniles.Este estudio tiene un doble objetivo. Primero, describir la prevalencia del consumo de sustancias y de otros trastornos mentales comórbidos en una muestra de adolescentes que consultan a un servicio de urgencias psiquiátricas. Segundo, analizar las diferencias clínicas y asistenciales entre el grupo de pacientes con patología dual (comorbilidad de trastorno mental y trastorno por uso de sustancias) y el grupo de pacientes con trastorno mental sin consumo.Se revisaron 4012 historias de adolescentes que acudieron a un servicio de urgencias de psiquiatría durante los años 2007-2009, obteniéndose una muestra de 1795 visitas. La muestra se dividió en dos grupos: el grupo de patología dual (n = 477) y el grupo de patología psiquiátrica (n = 1318). El grupo con patología dual representó el 26,5% de las urgencias analizadas. En comparación con el grupo de pacientes psiquiátricos, presentaba significativamente más trastornos de conducta, patología social, involuntariedad en las visitas, más ingresos y menor vinculación a la red asistencial.Los adolescentes con una patología dual generan un elevado impacto en los Servicios de Urgencia psiquiátricos infantojuveniles. Este grupo requiere de una atención especializada tanto en los servicios de urgencias como en unidades específicas. En consecuencia, los servicios de urgencias deben cumplir una triple función en el abordaje de pacientes con patología dual: la detección, la intervención breve y la derivación a unidades especializadas.

The Role of Diet in the Cardiovascular Health of Childhood Cancer Survivors-A Systematic Review.

BACKGROUND: Childhood cancer survivors (CCSs) face an increased risk of cardiovascular disease (CVD). This systematic review aims to provide the first synthesis of observational and interventional studies on the relationship between diet and cardiovascular health in CCSs. METHODS: A comprehensive search was conducted for studies published between 1990 and July 2023 in PubMed, MEDLINE, CINAHL, Child Development & Adolescent Studies, and Cochrane Library. Eligible studies included observational and interventional studies examining the associations or effects of dietary factors on CVD incidence, cardiac dysfunction, or CVD risk factors in CCSs diagnosed before age 25 years. RESULTS: Ten studies met the inclusion criteria (nine observational and one interventional). Collectively, they comprised 3485 CCSs (male, 1734; female, 1751). The outcomes examined across observational studies included characteristics of obesity, diabetes biomarkers, hypertension indicators, dyslipidaemia biomarkers, and metabolic syndrome. The evidence suggested that greater adherence to healthy diets was associated with lower body mass index, blood pressure, glucose, and triglycerides and higher high-density lipoprotein cholesterol. The 12-week lifestyle intervention study in childhood leukaemia survivors found no impact on obesity indicators. CONCLUSION: The review results indicate the potentially protective effects of healthy diets. However, the available research remains preliminary and limited, underscoring the need for more rigorous, adequately powered studies.

The effect of the Mid-Day Meal programme on the longitudinal physical growth from childhood to adolescence in India.

The study aims to examine the effect of the world's largest school-feeding programme, the Mid-Day Meal (MDM) programme, on the changes in the underweight prevalence among school-children in India. Data from the Indian Human Development Survey (IHDS) Rounds 1 (2004-05) and 2 (2011-12) were utilized. The sample included individual-level information of children aged 6 to 9 years in IHDS-1 who then turned 13 to 16 years in IHDS-2. The sample was categorised into four groups based on their MDM consumption history (Group 1: no MDM support in IHDS-1 and IHDS-2, Group 2: MDM support in IHDS-1, Group 3: MDM support in IHDS-2, Group 4: persistent MDM support in IHDS-1 and IHDS-2). The dependent variable was underweight status as defined by the World Health Organisation Child Growth Standards Body Mass Index for age (BMI Z-score) < -2 SD of the median. Bivariate analysis was used to examine the prevalence of underweight and establish associations between underweight status and socio-demographic characteristics. Logistic regression was performed to assess the strength of the association of socio-demographic characteristics and MDM consumption patterns with underweight across poor and non-poor asset groups. The findings suggest that early and persistent MDM support among respondents reduced the likelihood of low BMI Z-scores compared to those without MDM support. Respondents from the poor asset group who received MDM support in at least one of the two survey rounds had higher odds of being underweight in comparison with those who did not receive MDM support at all. Girls and adolescents residing in the Eastern region of India were less likely to be underweight. The study shows that the MDM programme was effective in reducing the rate of underweight among school children. However, continuous programme upscaling with a special focus on children from poor households will significantly benefit India's school-aged children.

A four-week dietary intervention with mycoprotein-containing food products reduces serum cholesterol concentrations in community-dwelling, overweight adults: A randomised controlled trial.

BACKGROUND: Substituting dietary meat and fish for mycoprotein, a fungal-derived food source rich in protein and fibre, decreases circulating cholesterol concentrations in laboratory-controlled studies. However, whether these findings can be translated to a home-based setting, and to decrease cholesterol concentrations in overweight and hypercholesterolemic individuals, remains to be established. OBJECTIVE: We investigated whether a remotely-delivered, home-based dietary intervention of mycoprotein-containing food products would affect various circulating cholesterol moieties and other markers of cardio-metabolic health in overweight (BMI >27.5 kg⋅m-2) and hypercholesterolaemic (>5.0 mmol⋅L-1) adults. METHODS: Seventy-two participants were randomized into a controlled, parallel-group trial conducted in a free-living setting, in which they received home deliveries of either meat/fish control products (CON; n = 39; BMI 33 ± 1 kg⋅m-2; 13 males, 26 females) or mycoprotein-containing food products (MYC; n = 33; BMI 32 ± 1 kg⋅m-2; 13 males, 20 females) for 4 weeks. Fingertip blood samples were collected and sent via postal service before and after the dietary intervention period and analysed for concentrations of serum lipids, blood glucose and c-peptide. RESULTS: Serum total cholesterol concentrations were unchanged throughout the intervention in CON, but decreased by 5 ± 2 % in MYC (from 5.4 ± 0.2 to 5.1 ± 0.2 mmol⋅L-1; P < 0.05). Serum low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol concentrations were also unchanged in CON, but decreased in MYC by 10 ± 3 % and 6 ± 2 % (both by 0.3 ± 0.1 mmol⋅L-1; P < 0.05). Serum high-density lipoprotein cholesterol and free triglyceride concentrations were unaffected in CON or MYC. Post-intervention, MYC displayed lower mean blood glucose (3.7 ± 0.2 versus 4.3 ± 0.2 mmol⋅L-1) and c-peptide (779 ± 76 vs. 1064 ± 86 pmol⋅L-1) concentrations (P < 0.05) vs. CON. CONCLUSIONS: We show that a home-based dietary intervention of mycoprotein-containing food products effectively lowers circulating cholesterol concentrations in overweight, hypercholesterolemic adults. This demonstrates that mycoprotein consumption is a feasible and ecologically valid dietary strategy to improve markers of cardio-metabolic health in an at-risk population under free living conditions. CLINICAL TRIAL REGISTRATION: NCT04773483 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT04773483).

Systematic review and meta-analysis: Associations of vitamin D with pulmonary function in children and young people with cystic fibrosis.

BACKGROUND: Increasing evidence suggests that vitamin D is associated with pulmonary health, which may benefit children and young people diagnosed with Cystic Fibrosis (cypCF). Therefore, the aim of this systematic review was to evaluate primary research to establish associations between 25OHD and pulmonary health in cypCF. METHODS: Electronic databases were searched with keywords related to CF, vitamin D, children/young people and pulmonary function. Included studies were cypCF (aged ≤21 years) treated in a paediatric setting. The primary outcome was lung function [forced expiratory volume in 1 s (FEV1% predicted)] and secondary outcomes were rate of pulmonary exacerbations, 25OHD status and growth. Evidence was appraised for risk of bias using the CASP tool, and quality using the EPHPP tool. A Meta-analysis was performed. RESULTS: Twenty-one studies were included with mixed quality ratings and heterogeneity of reported outcomes. The Meta-analysis including 5 studies showed a significantly higher FEV1% predicted in the 25OHD sufficiency compared to the deficiency group [FEV1% predicted mean difference (95% CI) was 7.71 (1.69-13.74) %; p = 0.01]. The mean ± SD FEV1% predicted for the sufficient (≥75 nmol/L) vs. deficient (<50 nmol/L) group was 94.7 ± 31.9% vs. 86.9 ± 13.2%; I2 = 0%; χ2 = 0.5; df = 4). Five studies (5/21) found significantly higher rate of pulmonary exacerbations in those who were 25OHD deficient when compared to the sufficient group and negative associations between 25OHD and FEV% predicted. The effects of vitamin D supplementation dosages on 25OHD status (10/21) varied across studies and no study (12/21) showed associations between 25OHD concentration and growth. CONCLUSION: This systematic review suggests that 25OHD concentration is positively associated with lung function and a concentration of >75 nmol/L is associated with reduced frequency of pulmonary exacerbations, which may slow lung function decline in cypCF. Future randomised clinical trials and mechanistic studies are warranted.

Vitamin D Status and Health Outcomes in School Children in Northern Ireland: Year One Results from the D-VinCHI Study.

(1) Background: Vitamin D status has never been investigated in children in Northern Ireland (UK). (2) Methods: Children (4-11 years) (n = 47) were recruited from November 2019 to March 2020 onto the cross-sectional study. Anthropometry was assessed. Plasma 25-hydroxyvitamin D (25(OH)D) was analysed. Vitamin D intake, parental knowledge and perceptions, participant habits, physical activity and sedentary behaviour were established via questionnaire. Muscle strength was assessed via isometric grip strength dynamometry and balance via dominant single-leg and tandem stance. Parathyroid hormone, bone turnover markers (OC, CTX and P1NP), glycated haemoglobin and inflammatory markers (CRP, IFN-γ, IL-10, IL-12p70, IL-13, IL-1ß, IL-2, IL-4, IL-6, IL-8 and TNF-α) were analysed. (3) Results: Mean (SD) 25(OH)D was 49.17 (17.04) nmol/L (n = 47); 44.7% of the children were vitamin D sufficient (25(OH)D >50 nmol/L), 48.9% were insufficient (25-50 nmol/L) and 6.4% were deficient (<25 nmol/L). 25(OH)D was positively correlated with vitamin D intake (µg/day) (p = 0.012, r = 0.374), spring/summer outdoor hours (p = 0.006, r = 0.402) and dominant grip strength (kg) (p = 0.044, r = 0.317). Vitamin D sufficient participants had higher dietary vitamin D intake (µg/day) (p = 0.021), supplement intake (µg/day) (p = 0.028) and spring/summer outdoor hours (p = 0.015). (4) Conclusion: Over half of the children were vitamin D deficient or insufficient. Wintertime supplementation, the consumption of vitamin D rich foods and spring/summer outdoor activities should be encouraged to minimise the risk of vitamin D inadequacy.