MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature.

Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition of histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent multi-subunit epigenetic regulator of gene expression and is responsible for histone 4 lysine 16 acetylation (H4K16ac). Using exome sequencing, here we identify a cohort of 25 individuals with heterozygous de novo variants in MSL complex member MSL2. MSL2 variants were associated with NDD phenotypes including global developmental delay, intellectual disability, hypotonia, and motor issues such as coordination problems, feeding difficulties, and gait disturbance. Dysmorphisms and behavioral and/or psychiatric conditions, including autism spectrum disorder, and to a lesser extent, seizures, connective tissue disease signs, sleep disturbance, vision problems, and other organ anomalies, were observed in affected individuals. As a molecular biomarker, a sensitive and specific DNA methylation episignature has been established. Induced pluripotent stem cells (iPSCs) derived from three members of our cohort exhibited reduced MSL2 levels. Remarkably, while NDD-associated variants in two other members of the MSL complex (MOF and MSL3) result in reduced H4K16ac, global H4K16ac levels are unchanged in iPSCs with MSL2 variants. Regardless, MSL2 variants altered the expression of MSL2 targets in iPSCs and upon their differentiation to early germ layers. Our study defines an MSL2-related disorder as an NDD with distinguishable clinical features, a specific blood DNA episignature, and a distinct, MSL2-specific molecular etiology compared to other MSL complex-related disorders.

De novo variants in ATP2B1 lead to neurodevelopmental delay.

Calcium (Ca2+) is a universal second messenger involved in synaptogenesis and cell survival; consequently, its regulation is important for neurons. ATPase plasma membrane Ca2+ transporting 1 (ATP2B1) belongs to the family of ATP-driven calmodulin-dependent Ca2+ pumps that participate in the regulation of intracellular free Ca2+. Here, we clinically describe a cohort of 12 unrelated individuals with variants in ATP2B1 and an overlapping phenotype of mild to moderate global development delay. Additional common symptoms include autism, seizures, and distal limb abnormalities. Nine probands harbor missense variants, seven of which were in specific functional domains, and three individuals have nonsense variants. 3D structural protein modeling suggested that the variants have a destabilizing effect on the protein. We performed Ca2+ imaging after introducing all nine missense variants in transfected HEK293 cells and showed that all variants lead to a significant decrease in Ca2+ export capacity compared with the wild-type construct, thus proving their pathogenicity. Furthermore, we observed for the same variant set an incorrect intracellular localization of ATP2B1. The genetic findings and the overlapping phenotype of the probands as well as the functional analyses imply that de novo variants in ATP2B1 lead to a monogenic form of neurodevelopmental disorder.

Exome sequencing in every pregnancy? Results of trio exome sequencing in structurally normal fetuses.

OBJECTIVE: This study aimed to assess the detection rate of clinically significant results of prenatal exome sequencing (pES) in low-risk pregnancies and apparently normal fetuses in non-consanguineous couples. METHODS: A retrospective analysis of pES conducted at a single center from January 2020 to September 2023 was performed. Genetic counseling was provided, and detailed medical histories were obtained. High-risk pregnancies were excluded due to major ultrasound anomalies, sonographic soft markers, abnormal maternal biochemical screening, or family history suggestive of monogenic diseases as well as cases with pathogenic and likely pathogenic (P/LP) chromosomal microarray results. Exome analysis focused on ∼2100 genes associated with Mendelian genetic disorders. Variant analysis and classification followed the American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS: Among 1825 pES conducted, 1020 low-risk cases revealed 28 fetuses (2.7%) with potentially clinically significant variants indicating known monogenic diseases, primarily de novo dominant variants (64%). Among these 28 cases, 9 fetuses (0.9%) had the potential for severe phenotypes, including shortened lifespan and intellectual disability, and another 12 had the potential for milder phenotypes. Seven cases were reported with variants of uncertain significance (VUS) that, according to the ACMG criteria, leaned toward LP, constituting 0.7% of the entire cohort. Termination of pregnancy was elected in 13 out of 1020 cases (1.2%) in the cohort, including 7/9 in the severe phenotypes group, 2/12 in the milder phenotype group, and 4/7 in the VUS group. CONCLUSION: The 2.7% detection rate highlights the significant contribution of pES in low-risk pregnancies. However, it necessitates rigorous analysis, and comprehensive genetic counseling before and after testing.

Telemedicine Versus Traditional In-Person Consultations: Comparison of Patient Satisfaction Rates.

Introduction: Data on patient satisfaction with the provision of genetic consultations using telemedicine are limited, especially those involving children. We compared patient satisfaction rates with telemedicine services versus traditional in-person encounters. Methods: A cross-sectional questionnaire-based study was conducted between January and June 2020. Questionnaires were distributed online to 1,672 consecutive patients who had received genetic counseling at our Genetics Institute in the clinical fields of adult and pediatric genetics, oncogenetics, and prenatal genetics, through in-person and/or telemedicine consultation. We used Likert scale with scores of 4-5 representing "satisfied"-"very satisfied" and 1-2 representing "very unsatisfied"-"unsatisfied." Results: The response rate was 27.3% (400 adults and 57 children <18 years), including 330 who had received in-person consultations (72.2%), 80 telemedicine consultations (17.5%), and 47 both consultations (10.3%). Mean satisfactory scores of 4-5 were reported by 82.1% in the in-person group versus 82.5% in the telemedicine group (p = 0.88). Mean scores of 1-2 were reported by 6.3% in the in-person group versus 11.2% in the telemedicine group (p = 0.31). No pediatric telemedicine group patient (n 12 = ) gave scores of 1-2 compared with 2/33 (6%) patients who had in-person pediatric consultations (p = 0.62). Most responders who had been counseled through telemedicine (n = 127, 84%) indicated willingness to use genetic services through telemedicine again. Conclusions: Users of genetic counseling through telemedicine, especially in the pediatric age group, were very satisfied at rates comparable to those of in-person consultations. Future research should evaluate patient compliance and views according to session type, information provided (e.g., diagnostic vs. negative results), and its nature (good vs. bad news).

Adolescent BMI and early-onset type 2 diabetes among Ethiopian immigrants and their descendants: a nationwide study.

BACKGROUND: We assessed in a nationwide cohort the association between adolescent BMI and early-onset (< 40 years) type 2 diabetes among Israelis of Ethiopian origin. METHODS: Normoglycemic adolescents (range 16-20 years old), including 93,806 native Israelis (≥ 3rd generation in Israel) and 27,684 Israelis of Ethiopian origin, were medically assessed for military service between 1996 and 2011. Weight and height were measured. Data were linked to the Israeli National Diabetes Registry. Incident type 2 diabetes by December 31, 2016 was the outcome. Cox regression models stratified by sex and BMI categories were applied. RESULTS: 226 (0.29%) men and 79 (0.18%) women developed diabetes during 992,980 and 530,814 person-years follow-up, respectively, at a mean age of 30.4 and 27.4 years, respectively. Among native Israeli men with normal and high (overweight and obese) BMI, diabetes incidence was 9.5 and 62.0 (per 105 person-years), respectively. The respective incidences were 46.9 and 112.3 among men of Ethiopian origin. After adjustment for sociodemographic confounders, the hazard ratios for type 2 diabetes among Ethiopian men with normal and high BMI were 3.4 (2.3-5.1) and 15.8 (8.3-30.3) respectively, compared to third-generation Israelis with normal BMI. When this analysis was limited to Israeli-born Ethiopian men, the hazard ratios were 4.4 (1.7-11.4) and 29.1 (12.9-70.6), respectively. Results persisted when immigrants of other white Caucasian origin were the reference; and among women with normal, but not high, BMI. CONCLUSIONS: Ethiopian origin is a risk factor for early-onset type 2 diabetes among young men at any BMI, and may require selective interventions.

The Knowledge and Attitudes of Pediatricians in Israel Towards Vegetarianism.

OBJECTIVES: Pediatricians have an important role in the dietary education of children, and in the nutritional health of their patients. We aimed to assess nutritional knowledge, familiarity with guidelines, and attitudes of pediatricians regarding vegetarian diets. METHODS: A cross-sectional study using a previously implemented questionnaire, distributed amongst a convenience sample of pediatricians in Israel. For each participant, scores of knowledge and of attitudes towards vegetarian diets were calculated. Scores were analyzed and compared between various categorizations of the respondents. RESULTS: Of 270 respondents (60.4% female individuals), 14.1% were following a vegetarian or semi-vegetarian diet. The overall mean scores for knowledge and attitude were 37.9 ±â€Š16.0% and 38.1 ±â€Š20.7%, respectively. Among pediatricians currently following a vegetarian or semi-vegetarian diet, mean knowledge and attitude scores were higher by 12.2% (95% confidence interval [CI] 6.8-17.6, P < 0.001) and 17.4% (95% CI 10.5-24.2, P < 0.001), respectively, compared with nonvegetarians. Knowledge scores were found to be positively correlated with attitude scores. Only 13.4% of pediatricians felt that their medical degree studies prepared them well to deal with vegetarian patients. A higher knowledge score was correlated with inquiring of patients eating habits, and counseling on vegetarian diets. CONCLUSIONS: Pediatricians possess a low average knowledge base in vegetarian nutrition. The majority of pediatricians do not hold positive attitudes concerning vegetarian diets. We show a positive correlation between overall knowledge and overall attitude for individual participants. Increasing the knowledge base of pediatricians regarding vegetarian diets may lead them to conceive meatless diets in a more positive light and better counsel their patients.

Severe obesity and cardio-metabolic comorbidities: a nationwide study of 2.8 million adolescents.

BACKGROUND: Severe obesity is rising among adolescents, but data on the prevalence of metabolic abnormalities among this group are limited. We assessed the secular trend of severe obesity and its association with major cardio-metabolic morbidities. METHODS: A total of 2,785,227 Israeli adolescents (aged 17.2 ± 0.5 years) who underwent a pre-recruitment medical examination including routine measurements of weight, height and blood pressure between 1967 and 2015 were included. In all, 230,639 adolescents with abnormally excessive BMI were classified into overweight, classes I, II, and III (severe) obesity. Logistic regression was applied to determine the association between BMI groups and prehypertension, high blood pressure and type 2 diabetes (T2DM). RESULTS: There was 45-fold increase in the prevalence of class III obesity during study period. Severe obesity was recorded in 2060 males and 1149 females, in whom nearly 35 and 43% had prehypertension or high blood pressure, respectively. Compared with adolescents with overweight, the odds ratios (ORs) for high blood pressure in classes II and III obesity groups, respectively, were 2.13 (95% CI, 2.04-2.23) and 2.86 (2.60-3.15) in males, and 2.59 (2.43-2.76) and 3.44 (3.04-3.90) in females, whereas the ORs for T2DM were 19.1 (12.3-29.6) and 38.0 (22.6-64.0) in males, and 15.1 (11.4-20.0) and 24.8 (17.2-35.7) in females. Results persisted in extensive sensitivity analyses including a longitudinal follow-up (median: males, 3.4 years; females, 4.9 years). CONCLUSIONS: Severe obesity showed a marked secular increase and was associated with significantly higher risk for abnormal blood pressure and T2DM than lower degrees of obesity, in both males and females.

Frequency, comprehension and attitudes of physicians towards abbreviations in the medical record.

AIMS: Abbreviations are common in the medical record. Their inappropriate use may ultimately lead to patient harm, yet little is known regarding the extent of their use and their comprehension. Our aim was to assess the extent of their use, their comprehension and physicians' attitudes towards them, using ophthalmology consults in a tertiary hospital as a model. METHODS: We first mapped the frequency with which English abbreviations were used in the departments' computerised databases. We then used the most frequently used abbreviations as part of a cross-sectional survey designed to assess the attitudes of non-ophthalmologist physicians towards the abbreviations and their comprehension of them. Finally, we tested whether an online lecture would improve comprehension. RESULTS: 4375 records were screened, and 235 physicians responded to the survey. Only 42.5% knew at least 10% of the abbreviations, and no one knew them all. Ninety-two per cent of respondents admitted to searching online for the meanings of abbreviations, and 59.1% believe abbreviations should be prohibited in medical records. A short online lecture improved the number of respondents answering correctly at least 50% of the time from 1.2% to 42% (P<0.001). CONCLUSIONS: Abbreviations are common in medical records and are frequently misinterpreted. Online teaching is a valuable tool for physician education. The majority of respondents believed that misinterpreting abbreviations could negatively impact patient care, and that the use of abbreviations should be prohibited in medical records. Due to low rates of comprehension and negative attitudes towards abbreviations in medical communications, we believe their use should be discouraged.

Detecting intentional insulin omission for weight loss in girls with type 1 diabetes mellitus.

OBJECTIVE: Intentional insulin omission is a unique inappropriate compensatory behavior that occurs in patients with type 1 diabetes mellitus, mostly in females, who omit or restrict their required insulin doses in order to lose weight. Diagnosis of this underlying disorder is difficult. We aimed to use clinical and laboratory criteria to create an algorithm to assist in the detection of intentional insulin omission. METHOD: The distribution of HbA1c levels from 287 (181 females) patients with type 1 diabetes were used as reference. Data from 26 patients with type 1 diabetes and intentional insulin omission were analysed. The Weka (Waikato Environment for Knowledge Analysis) machine learning software, decision tree classifier with 10-fold cross validation was used to developed prediction models. Model performance was assessed by cross-validation in a further 43 patients. RESULTS: Adolescents with intentional insulin omission were discriminated by: female sex, HbA1c>9.2%, more than 20% of HbA1c measurements above the 90th percentile, the mean of 3 highest delta HbA1c z-scores>1.28, current age and age at diagnosis. The models developed showed good discrimination (sensitivity and specificity 0.88 and 0.74, respectively). The external test dataset revealed good performance of the model with a sensitivity and specificity of 1.00 and 0.97, respectively. DISCUSSION: Using data mining methods we developed a clinical prediction model to determine an individual's probability of intentionally omitting insulin. This model provides a decision support system for the detection of intentional insulin omission for weight loss in adolescent females with type 1 diabetes mellitus.

The Global Spread of Severe Obesity in Toddlers, Children, and Adolescents: A Systematic Review and Meta-Analysis.

INTRODUCTION: Severe obesity among children and adolescents has emerged as a public health concern in multiple places around the world. METHODS: We searched the Medline database for articles on severe obesity rates in children published between January 1960 and January 2020. For studies with available prevalence rates for an early and a more recent time period, the relative increase in prevalence was imputed. RESULTS: In total, 874 publications were identified, of which 38 contained relevant epidemiological data. Rates of severe obesity varied significantly according to age, gender, geographic area, and the definition of severe obesity. The highest rates of class II and III obesity in the USA according to the Centers of Disease Control cut-off were 9.5% and 4.5%, respectively. Seventeen studies reported prevalence rates in at least two time periods. Data for 9,190,718 individuals showed a 1.71 (95% CI, 1.53-1.90) greater odds for severe obesity in 2006-2017 (N = 5,029,584) versus 1967-2007 (N = 4,161,134). In an analysis limited to studies from 1980s with a minimum follow-up of 20 years, a 9.16 (95% CI, 7.76-10.80) greater odds for severe obesity in recent versus earlier time was found. An analysis limited to studies from 2000, with a follow-up of 5-15 years, a 1.09 (95% CI, 0.99-1.20) greater odds was noted when comparing (2011-2017; N = 4,991,831) versus (2000-2011; N = 4,134,340). CONCLUSION: Severe pediatric obesity is escalating with a marked increase from the 1980s and a slower rate from 2000.

Progression of Pediatric Keratoconus After Corneal Cross-Linking: A Systematic Review and Pooled Analysis.

PURPOSE: Corneal collagen cross-linking (CXL) is an effective treatment to slow down keratoconus (KC) progression in adults. Several studies have also shown efficacious outcomes in pediatric populations, yet no systematic analysis has been performed and no accepted definition for progression is available in children after CXL. This study aimed to establish the most commonly used criteria for progression and to conduct a systematic review of the literature with pooled analysis to assess children's keratoconus progression after CXL. METHODS: A systemic literature review combined with pooled analysis was performed on full-length studies of KC after CXL treatment in a pediatric population and the methods used to report progression were analyzed. RESULTS: Thirty-seven studies (2078 eyes) were identified on the rates of KC progression after CXL. The most common method to report progression was increased Kmax, Kmean, or Ksteep by ≥1.0 diopter (78.3% of studies). Using these criteria, the mean pooled progression rate after epithelium-off CXL was 9.9% (95% confidence interval: 6.1% -14.6%, total pooled sample size: 1508 eyes) with high heterogeneity between studies [I 2 = 86.48% (95% confidence interval: 80.98 - 90.39), P < 0.0001]. CONCLUSIONS: When considering KC progression after CXL in children, with an increase in Kmax, Kmean, or Ksteep ≥ 1.0 diopter, the progression risk was roughly 10%. We encourage clear quantitative reporting of KC progression in future studies evaluating CXL efficacy in pediatric populations.

Maternal Exposure to Polychlorinated Biphenyls and Asthma, Allergic Rhinitis and Atopic Dermatitis in the Offspring: The Environmental Health Fund Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are persistent organic pollutants banned for use worldwide. Due to their biodegradation resistance, they accumulate along the food chain and in the environment. Maternal exposure to PCBs may affect the fetus and the infant. PCBs are immunotoxic and may damage the developing immune system. PCBs are associated with elevated IgE antibodies in cord blood and are considered to be predictive of atopic reactions. Several studies on the association between prenatal exposure to PCBs and atopic reactions were previously published, albeit with conflicting results. Objectives: To examine the association between maternal PCBs levels and atopic reactions in their offspring. Methods: During the years 2013-2015, a prospective birth cohort was recruited at the delivery rooms of Shamir Medical Center (Assaf Harofeh) and "Dana Dwek" Children's Hospital. Four PCBs congeners were investigated: PCBs 118, 138, 153, and 180. In 2019, when children reached the age of 4-6 years, mothers were interviewed using the ISAAC questionnaire to assess symptoms of atopic reactions, including asthma, allergic rhinitis, and atopic dermatitis. Results: One hundred and fifty mother-child dyads were analyzed. No significant differences were found in the median serum PCBs concentrations of each studied congener or total PCBs for asthma, allergic rhinitis, atopic dermatitis diagnosis, or parent-reported symptoms. No association was found between exposure to total PCBs and the risk for asthma symptoms or diagnosis, adjusted to maternal age and family member with atopic condition: aOR = 0.94, 95%CI: (0.88; 0.99). No association was observed between each studied PCB congener and asthma symptoms or diagnosis. The same results were found also for other studied outcomes-allergic rhinitis and atopic dermatitis. Conclusion: Our study joins a series of previous studies that attempt to shed light on environmental exposures in utero as influencing factors for atopic conditions in children. Our results reflect the complexity of the pathophysiology of these phenomena. No relationship between maternal serum PCBs levels was demonstrated for asthma, allergic rhinitis, or atopic dermatitis. However, additional multi-participant studies, with longer, spanning into later pediatric age follow up are needed.

Questioning the Value of Brain Magnetic Resonance Imaging in the Evaluation of Children with Isolated Growth Hormone Deficiency.

BACKGROUND: Isolated growth hormone deficiency (IGHD) is a relatively common disorder. Current diagnostic protocol requires a brain magnetic resonance imaging (MRI) study of the hypothalamus and the hypophysis to determine the cause after establishment of the diagnosis. This study aimed to examine the yield of brain MRI in the evaluation of children with IGHD and to define clinical and laboratory parameters that justify its performance. METHODS: A retrospective chart review of all children (<18 years) diagnosed with IGHD was conducted at 3 pediatric endocrinology units between 2008 and 2018. RESULTS: The study included 192 children (107 boys) with confirmed IGHD. The mean age ± standard deviation (SD) at diagnosis was 8.2 ± 3.7 years (median 8.5 years, range 0.8-15.9). The mean height SD score (SDS) at diagnosis was -2.25 ± 0.73. The mean height deficit SDS (defined as the difference between height SDS at diagnosis and mid-parental height SDS) was -1.7 ± 0.9. Fifteen children (7.8%) had pathological MRI findings. No space-occupying lesion was detected. Children with pathological MRIs had greater height deficit SDS and lower peak growth hormone levels on provocative tests compared to children with normal MRIs: -2.3 ± 1.2 vs. -1.6 ± 0.8 (p = 0.02) and 4.4 ± 1.9 vs. 5.7 ± 1.3 (p = 0.01), respectively. CONCLUSION: Our preliminary data indicate that most brain MRIs performed for routine evaluation of children with IGHD are not essential for determining cause. Further studies with larger cohorts are needed in order to validate this proposed revision of current protocols.

Paediatricians' attitudes and beliefs towards transgender people: a cross-sectional survey in Israel.

OBJECTIVE: The number of transgender and gender non-conforming children is on the rise. For these children, the timing of medical intervention is crucial, yet transgender children report poorer overall physical and mental health outcomes compared with their cisgender peers. We aim to describe how paediatricians perceive transgender people. SETTING: The 'Transgender Attitudes and Beliefs Scale', which consists of 29 items in three domains-human value, interpersonal comfort and sex/gender beliefs-was administered to 391 senior and resident paediatricians in Israel. The responses on a 7-point Likert scale were collapsed into two categories: a mean score of ≥6 for each domain was a 'Favourable' perception and <6 'Unfavourable'. RESULTS: Of 355 respondents (91% response rate), 221 (62%) were females, 132 (37%) were males and 2 identified as 'other'; 290 (82%) were born in 'trans-respect countries', 274 (77%) identified as secular, 223 (63%) were senior physicians and 132 (27%) were residents. Overall, 90% of the cohort scored favourably on the 'Human value' domain, 68% on 'Interpersonal comfort' and 40% on 'Sex/gender beliefs'. In the 'Interpersonal comfort' domain, being a man, birthplace in a transphobic country, identification as religious and being a senior physician were all associated with increased ORs for an unfavourable score: 2.1 (95% CI 1.3 to 3.4), 3.4 (95% CI 1.9 to 6.3), 2.4 (95% CI 1.4 to 4.2) and 1.8 (95% CI 1.1 to 3.0), respectively. In the 'Sex/gender beliefs' domain, being a man and identifying as religious had significantly increased ORs for unfavourable scores: 2.2 (95% CI 1.3 to 3.5) and 10.6 (95% CI 4.7 to 24.1), respectively. CONCLUSIONS: Negative attitudes towards transgender people are still widespread among paediatricians. Interventions are warranted to positively impact these attitudes.

Socioeconomic inequalities and severe obesity-Sex differences in a nationwide study of 1.12 million Israeli adolescents.

INTRODUCTION: In a nationwide population of adolescents, we investigated the sex-specific association of socioeconomic position (SEP) with severe obesity, and trends over time. METHODS: The cohort comprises all Israeli adolescents (mean ± SD age 17.3 ± 0.5 years) who were medically examined, before mandatory military service during 2000 to 2015. Of 1 120 362 adolescents, 239 816 (21.4%) were classified with overweight or with obesity classes I to III using the International Obesity Task Force criteria. Data were compared between 2000 to 2009 and 2010 to 2015. RESULTS: Considering more advantaged residential SEP as the reference group, the respective odds ratios (ORs ± 95%CI) of less advantaged SEP for obesity classes I to III in 2010 to 2015 were 1.48 (1.40-1.56), 1.66 (1.51-1.83), and 1.73 (1.45-2.08) for males; and 1.72 (1.60-1.84), 1.89 (1.66-2.15), and 2.62 (2.04-3.37) for females. All point estimates were higher than in the preceding decade. Considering female inductees from the more advantaged SEP as the reference group, ORs were higher for males in the more advantaged SEP group, for overweight, 1.31 (1.27-1.36); class I obesity, 1.29 (1.20-1.38); class II obesity, 1.34 (1.18-1.53); and class III obesity, 1.60 (1.24-2.07). Similarly, in the less and medium advantaged SEP groups, increased ORs for males compared with females were observed in all obesity groups. Results persisted using United States Centers for Disease Control and Prevention growth charts. CONCLUSIONS: Adolescents with less rather than more advantaged residential SEP are at greater risk of severe obesity. Adolescent males, of all residential SEP groups had higher odds than females for all classes of obesity.

Impact of Immigration on Body Mass Index and Blood Pressure Among Adolescent Males and Females: A Nationwide Study.

Immigration from one cultural milieu to another has been associated with a greater risk for incident cardio-metabolic morbidity among adults. In this nationwide, population-based, cross-sectional study of data recorded from 1992 to 2016, we assessed the association between body mass index and blood pressure levels among adolescent immigrants, aged 16 to 19 years, of Ethiopian origin, and their secular trend of overweight and obesity. Adolescents of Ethiopian origin were classified as Israeli-born (n=16 153) or immigrants (N=23 487), with stratification by age at immigration. Adolescents whose fathers were at least 3 generations in Israel (n=277 789) served as a comparative group. Hypertensive-range blood pressure values adjusted for age, sex, and height served as outcome. Among adolescents of Ethiopian origin, overweight and obesity (body mass index ≥85th percentile), increased by 2.5 and 4-fold in males and females, respectively, during the study period, compared with a 1.5-fold increase among native Israeli-born males and females. The odds for hypertensive-range measurements increased with the length of residence in Israel: 7.3%, 10.6%, and 14.4% among males who immigrated at ages 12 to 19, 6 to 11.9, and 0 to 5.9 years, respectively; and 11.5%, 16.7%, and 19.3%, respectively, among females. Israeli-born Ethiopians had a significantly higher risk for hypertensive-range measurements at any body mass index level compared with native Israeli-born examinees, after adjusting for sociodemographic factors and health status. In conclusion, among Ethiopian Israeli adolescents, abnormal blood pressure correlates directly with the time-lapse since immigration. Immigrant populations require targeted surveillance and appropriate intervention.

Diagnostic markers of acute infections in infants aged 1 week to 3 months: a retrospective cohort study.

OBJECTIVE: History and physical examination do not reliably exclude serious bacterial infections (SBIs) in infants. We examined potential markers of SBI in young febrile infants. DESIGN: We reviewed white cell count (WBC), absolute neutrophil count (ANC), neutrophil to lymphocyte count ratio (NLR) and C reactive protein (CRP) in infants aged 1 week to 90 days, admitted for fever to one medical centre during 2012-2014. RESULTS: SBI was detected in 111 (10.6%) of 1039 infants. Median values of all investigated diagnostic markers were significantly higher in infants with than without SBI: WBC (14.4 vs 11.4 K/µL, P<0.001), ANC (5.8 vs 3.7 K/µL, P<0.001), CRP (19 vs 5 mg/L, P <0.001) and NLR (1.2 vs 0.7, P<0.001). Areas under the receiver operating characteristic curve (AUC) for discriminating SBI were: 0.65 (95% CI 0.59 to 0.71), 0.69 (95% CI 0.63 to 0.74), 0.71 (95% CI 0.65 to 0.76) and 0.66 (95% CI 0.60 to 0.71) for WBC, ANC, CRP and NLR, respectively. Logistic regression showed the best discriminative ability for the combination of CRP and ANC, with AUC: 0.73 (95% CI 0.67 to 0.78). For invasive bacterial infection, AUCs were 0.70 (95% CI 0.56 to 0.85), 0.80 (95% CI 0.67 to 0.92), 0.78 (95% CI 0.68 to 0.89) and 0.78 (95% CI 0.66 to 0.90), respectively. CRP combined with NLR or ANC were the best discriminators of infection, AUCs: 0.82 (95% CI 0.70 to 0.95) and 0.82 (95% CI 0.68 to 0.95), respectively. CONCLUSIONS: Among young febrile infants, CRP was the best single discriminatory marker of SBI, and ANC was the best for invasive bacterial infection. ANC and NLR can contribute to evaluating this population.