Improving screening for malnourished children at high risk of death: A study of children aged 6-59 months in rural Senegal

OBJECTIVE: To investigate whether children with concurrent wasting and stunting require therapeutic feeding and to better understand whether multiple diagnostic criteria are needed to identify children with a high risk of death and in need of treatment. DESIGN: Community-based cohort study, following 5751 children through time. Each child was visited up to four times at 6-month intervals. Anthropometric measurements were taken at each visit. Survival was monitored using a demographic surveillance system operating in the study villages. SETTING: Niakhar, a rural area of the Fatick region of central Senegal.ParticipantsChildren aged 6-59 months living in thirty villages in the study area. RESULTS: Weight-for-age Z-score (WAZ) and mid-upper arm circumference (MUAC) were independently associated with near-term mortality. The lowest WAZ threshold that, in combination with MUAC, detected all deaths associated with severe wasting or concurrent wasting and stunting was WAZ = 115 mm may require lower-intensity treatment than children identified using MUAC<115 mm. CONCLUSIONS: A combination of MUAC and WAZ detected all near-term deaths associated with severe anthropometric deficits including concurrent wasting and stunting. Therapeutic feeding programmes may achieve higher impact if WAZ and MUAC admission criteria are used

Changing sex differences in undernutrition of African children: findings from Demographic and Health Surveys.

The study investigates sex differences in the prevalence of undernutrition in sub-Saharan Africa. Undernutrition was defined by Z-scores using the CDC-2000 growth charts. Some 128 Demographic and Health Surveys (DHS) were analysed, totalling 700,114 children under-five. The results revealed a higher susceptibility of boys to undernutrition. Male-to-female ratios of prevalence averaged 1.18 for stunting (height-for-age Z-score <-2.0); 1.01 for wasting (weight-for-height Z-score <-2.0); 1.05 for underweight (weight-for-age Z-score <-2.0); and 1.29 for concurrent wasting and stunting (weight-for-height and height-for-age Z-scores <-2.0). Sex ratios of prevalence varied with age for stunting and concurrent wasting and stunting, with higher values for children age 0-23 months and lower values for children age 24-59 months. Sex ratios of prevalence tended to increase with declining level of mortality for stunting, underweight and concurrent wasting and stunting, but remained stable for wasting. Comparisons were made with other anthropometric reference sets (NCHS-1977 and WHO-2006), and the results were found to differ somewhat from those obtained with CDC-2000. Possible rationales for these patterns are discussed

Boys are more likely to be undernourished than girls: A systematic review and meta-analysis of sex differences in undernutrition

AbstractBackgroundExcess male morbidity and mortality is well recognised in neonatal medicine and infant health. In contrast, within global nutrition, it is commonly assumed that girls are more at-risk of experiencing undernutrition. We aimed to explore evidence for any male/female differences in child undernutrition using anthropometric case definitions and the reasons for differences observed.MethodsWe searched: Medline, Embase, Global health, Popline and Cochrane databases with no time limits applied. Eligible studies focused on children aged 0-59 months affected by undernutrition where sex was reported. In the meta-analysis, undernutrition-specific estimates were examined separately for wasting, stunting and underweight using a random effects model.Results76 studies were identified: 46/76 studies were included in the meta-analysis. In 20 which examined wasting, boys had higher odds of being wasted than girls (pooled OR 1.26, 95% CI 1.13-1.40). 39 examined stunting: boys had higher odds of stunting than girls (pooled OR 1.31 95% CI 1.24-1.39). 25 explored underweight: boys had higher odds of being underweight than girls (pooled OR 1.19, 95% CI 1.07-1.32). There was some limited evidence that the female advantage indicating lower risk of stunting and underweight was weaker in South Asia than other parts of the world.44/76 (58%) studies discussed possible reasons for boy/girl differences; 11/76 (14%) cited studies with similar findings with no further discussion; 21/76 (28%) had no sex difference discussion. 6/44 studies (14%) postulated biological causes, 21/44 (48%) social causes and 17/44 (38%) to a combination.ConclusionOur review indicates that undernutrition in children under 5 is more likely to affect boys than girls, though the magnitude of these differences varies and is more pronounced in some contexts than others. Future research should further explore reasons for these differences and implications for nutrition policy and practice.Key QuestionsWhat is already known?Undernutrition (wasting, stunting, and underweight) is a public health problem affecting millions of children aged under 5 years globally.Although higher neonatal and infant morbidity/mortality for boys is well described, little attention has been given to sex differences in the field of undernutrition due to an assumption that girls are very often disadvantaged over boys.What are the new findings?In most settings studied, undernutrition is more common among boys than girls, though the extent of these differences varies and is reversed in a few contexts.Both biological and social mechanisms have been proposed to be responsible for the observed differences as well as a combination of the two.What do the new findings imply?Greater awareness of actual sex differences is needed within the field of nutrition. While sex-specific data is routinely analysed and reported in nutrition surveys it should be used in nutrition programming to better identify and understand what differences exist. Analysis should assess if the sex balance in programme admissions is reflective of the population undernutrition burden.Further research is needed to understand the mechanisms that lead to sex and gender differences in undernutrition and their implications. Better epidemiological understanding is a priority, as is work to explore their consequent effects on morbidity and mortality.</jats:sec

Strategies for Biochemical and Pathologic Quality Assurance in a Large Multi-Institutional Biorepository; The Experience of the PROCURE Quebec Prostate Cancer Biobank

Well-characterized, high-quality fresh-frozen prostate tissue is required for prostate cancer research. As part of the PROCURE Prostate Cancer Biobank launched in 2007, four University Hospitals in Quebec joined to bank fresh frozen prostate tissues from radical prostatectomies (RP). As the biobank progressed towards allocation, the nature and quality of the tissues were determined. RP tissues were collected by standardized alternate mirror-image or biopsy-based targeted methods, and frozen for banking. Clinical/pathological parameters were captured. For quality control, two presumed benign and two presumed cancerous frozen, biobanked tissue blocks per case (10/site) were randomly selected during the five years of collection. In a consensus meeting, 4 pathologists blindly evaluated slides (n = 160) and graded quality, Gleason score (GS), and size of cancer foci. The quality of tissue RNA (37/40 cases) was assessed using the RNA Integrity Number. The biobank included 1819 patients of mean age: 62.1 years; serum PSA: 8ng/ml; prostate weight: 47.8 g; GS: 7; and pathological stage: T2 in 64.5%, T3A in 25.5% and T3B in 10% of cases. Of the 157 evaluable slides, 79 and 78 had benign and cancer tissue, respectively. GS for the 37 cancer-positive cases were: 6 in 9, 7 in 18 and &gt; 7 in 10 and, in most instances, in concordance with final GS. In 40% of slides containing cancer, foci occupied ‡ 50% of block surface and 42% had a diameter ‡ 1 cm. Tissue was well preserved and consistently yielded RNA of very good quality with RNA Integrity Number (RIN) &gt; 7 for 97% of cases (mean = 8.7 -0.7) during the five-year collection period. This study confirms the high quality of randomly selected benign and cancerous fresh-frozen prostate tissues of the PROCURE Quebec Prostate Cancer Biobank. These results strengthen the uniqueness of this large prospective resource for prostate cancer research

Understanding Sex Differences in Childhood Undernutrition: A Narrative Review.

Complementing a recent systematic review and meta-analysis which showed that boys are more likely to be wasted, stunted, and underweight than girls, we conducted a narrative review to explore which early life mechanisms might underlie these sex differences. We addressed different themes, including maternal and newborn characteristics, immunology and endocrinology, evolutionary biology, care practices, and anthropometric indices to explore potential sources of sex differences in child undernutrition. Our review found that the evidence on why sex differences occur is limited but that a complex interaction of social, environmental, and genetic factors likely underlies these differences throughout the life cycle. Despite their bigger size at birth and during infancy, in conditions of food deprivation, boys experience more undernutrition from as early as the foetal period. Differences appear to be more pronounced in more severe presentations of undernutrition and in more socioeconomically deprived contexts. Boys are more vulnerable to infectious disease, and differing immune and endocrine systems appear to explain some of this disadvantage. Limited evidence also suggests that different sociological factors and care practices might exert influence and have the potential to exacerbate or reverse observed differences. Further research is needed to better understand sex differences in undernutrition and the implications of these for child outcomes and prevention and treatment programming

Prior Stroke in PFO Patients Is Associated With Both PFO-Related and -Unrelated Factors.

Background and Purpose: To identify factors associated with prior stroke at presentation in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO). Methods: We studied cross-sectional data from the International PFO Consortium Study (NCT00859885). Patients with first-ever stroke and those with prior stroke at baseline were analyzed for an association with PFO-related (right-to-left shunt at rest, atrial septal aneurysm, deep venous thrombosis, pulmonary embolism, and Valsalva maneuver) and PFO-unrelated factors (age, gender, BMI, hypertension, diabetes mellitus, hypercholesterolemia, smoking, migraine, coronary artery disease, aortic plaque). A multivariable analysis was used to adjust effect estimation for confounding, e.g., owing to the age-dependent definition of study groups in this cross-sectional study design. Results: We identified 635 patients with first-ever and 53 patients with prior stroke. Age, BMI, hypertension, diabetes mellitus, hypercholesterolemia, coronary artery disease, and right-to-left shunt (RLS) at rest were significantly associated with prior stroke. Using a pre-specified multivariable logistic regression model, age (Odds Ratio 1.06), BMI (OR 1.06), hypercholesterolemia (OR 1.90) and RLS at rest (OR 1.88) were strongly associated with prior stroke.Based on these factors, we developed a nomogram to illustrate the strength of the relation of individual factors to prior stroke. Conclusion: In patients with CS and PFO, the likelihood of prior stroke is associated with both, PFO-related and PFO-unrelated factors

Streptococcal peritonitis in Australian peritoneal dialysis patients: predictors, treatment and outcomes in 287 cases

Background There has not been a comprehensive, multi-centre study of streptococcal peritonitis in patients on peritoneal dialysis (PD) to date. Methods The predictors, treatment and clinical outcomes of streptococcal peritonitis were examined by binary logistic regression and multilevel, multivariate poisson regression in all Australian PD patients involving 66 centres between 2003 and 2006. Results Two hundred and eighty-seven episodes of streptococcal peritonitis (4.6% of all peritonitis episodes) occurred in 256 individuals. Its occurrence was independently predicted by Aboriginal or Torres Strait Islander racial origin. Compared with other organisms, streptococcal peritonitis was associated with significantly lower risks of relapse (3% vs 15%), catheter removal (10% vs 23%) and permanent haemodialysis transfer (9% vs 18%), as well as a shorter duration of hospitalisation (5 vs 6 days). Overall, 249 (87%) patients were successfully treated with antibiotics without experiencing relapse, catheter removal or death. The majority of streptococcal peritonitis episodes were treated with either intraperitoneal vancomycin (most common) or first-generation cephalosporins for a median period of 13 days (interquartile range 8–18 days). Initial empiric antibiotic choice did not influence outcomes. Conclusion Streptococcal peritonitis is a not infrequent complication of PD, which is more common in indigenous patients. When treated with either first-generation cephalosporins or vancomycin for a period of 2 weeks, streptococcal peritonitis is associated with lower risks of relapse, catheter removal and permanent haemodialysis transfer than other forms of PD-associated peritonitis.Stacey O'Shea, Carmel M Hawley, Stephen P McDonald, Fiona G Brown, Johan B Rosman, Kathryn J Wiggins, Kym M Bannister and David W Johnso

Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa

Retinitis pigmentosa (RP) is the most frequent form of inherited retinal dystrophy. RP is genetically heterogeneous and the genes identified to date encode proteins involved in a wide range of functional pathways, including photoreceptor development, phototransduction, the retinoid cycle, cilia, and outer segment development. Here we report the identification of biallelic mutations in Receptor Expression Enhancer Protein 6 (REEP6) in seven individuals with autosomal-recessive RP from five unrelated families. REEP6 is a member of the REEP/Yop1 family of proteins that influence the structure of the endoplasmic reticulum but is relatively unstudied. The six variants identified include three frameshift variants, two missense variants, and a genomic rearrangement that disrupts exon 1. Human 3D organoid optic cups were used to investigate REEP6 expression and confirmed the expression of a retina-specific isoform REEP6.1, which is specifically affected by one of the frameshift mutations. Expression of the two missense variants (c.383C>T [p.Pro128Leu] and c.404T>C [p.Leu135Pro]) and the REEP6.1 frameshift mutant in cultured cells suggest that these changes destabilize the protein. Furthermore, CRISPR-Cas9-mediated gene editing was used to produce Reep6 knock-in mice with the p.Leu135Pro RP-associated variant identified in one RP-affected individual. The homozygous knock-in mice mimic the clinical phenotypes of RP, including progressive photoreceptor degeneration and dysfunction of the rod photoreceptors. Therefore, our study implicates REEP6 in retinal homeostasis and highlights a pathway previously uncharacterized in retinal dystrophy

Spectrum of congenital anomalies among VACTERL cases: a EUROCAT population-based study

Background: The VACTERL (Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, Limb abnormalities) association is the non-random occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheo-esophageal, renal, and limb anomalies. Diagnosing VACTERL patients is difficult, as many disorders have multiple features in common with VACTERL. The aims of this study were to clearly outline component features, describe the phenotypic spectrum among the largest group of VACTERL patients thus far reported, and to identify phenotypically similar subtypes. Methods: A case-only study was performed assessing data on 501 cases recorded with VACTERL in the JRC-EUROCAT (Joint Research Centre-European Surveillance of Congenital Anomalies) central database (birth years: 1980–2015). We differentiated between major and minor VACTERL features and anomalies outside the VACTERL spectrum to create a clear definition of VACTERL. Results: In total, 397 cases (79%) fulfilled our VACTERL diagnostic criteria. The most commonly observed major VACTERL features were anorectal malformations and esophageal atresia/tracheo-esophageal fistula (both occurring in 62% of VACTERL cases), followed by cardiac (57%), renal (51%), vertebral (33%), and limb anomalies (25%), in every possible combination. Three VACTERL subtypes were defined: STRICT-VACTERL, VACTERL-LIKE, and VACTERL-PLUS, based on severity and presence of additional congenital anomalies. Conclusion: The clearly defined VACTERL component features and the VACTERL subtypes introduced will improve both clinical practice and etiologic research.acceptedVersio