Malnutrition, poor food intake, and adverse healthcare outcomes in non-critically ill obese acute care hospital patients

Obesity, defined as a BMI\ua0≥\ua030\ua0kg/m, has demonstrated protective associations with mortality in some diseases. However, recent evidence demonstrates that poor nutritional status in critically ill obese patients confounds this relationship. The purpose of this paper is to evaluate if poor nutritional status, poor food intake and adverse health-related outcomes have a demonstrated association in non-critically ill obese acute care hospital patients.This is a secondary analysis of the Australasian Nutrition Care Day Survey dataset (N\ua0=\ua03122), a prospective cohort study conducted in hospitals from Australia and New Zealand in 2010. At baseline, hospital dietitians recorded participants' BMI, evaluated nutritional status using Subjective Global Assessment (SGA), and recorded 24-h\ua0food intake (as 0%, 25%, 50%, 75%, and 100% of the offered food). Post-three months, participants' length of stay (LOS), readmissions, and in-hospital mortality data were collected. Bivariate and regression analyses were conducted to investigate if there were an association between BMI, nutritional status, poor food intake, and health-related outcomes.Of the 3122 participants, 2889 (93%) had eligible data. Obesity was prevalent in 26% of the cohort (n\ua0=\ua0750; 75% females; 61\ua0±\ua015 years; 37\ua0±\ua07\ua0kg/m). Fourteen percent (n\ua0=\ua0105) of the obese patients were malnourished. Over a quarter of the malnourished obese patients (N\ua0=\ua030/105, 28%) consumed ≤25% of the offered meals. Most malnourished obese patients (74/105, 70%) received standard diets without additional nutritional support. After controlling for confounders (age, disease type and severity), malnutrition and intake ≤25% of the offered meals independently trebled the odds of in-hospital mortality within 90 days of hospital admission in obese patients.Although malnourished obese experienced significantly adverse health-related outcomes they were least likely to receive additional nutritional support. This study demonstrates that BMI alone cannot be used as a surrogate measure for nutritional status and warrants routine nutritional screening for all hospital patients, and subsequent nutritional assessment and support for malnourished patients

Development of advanced practice competency standards for dietetics in Australia

Aim: This study aimed to explore the work roles, major tasks and core activities of advanced practice dietitians in Australia to define the Competency Standards for advanced practice. Methods: A qualitative approach was used to review advanced dietetic practice in Australia involving experienced professionals, mostly dietitians. Four focus groups were conducted with a total of 17 participants and an average of 20 years experience: 15 dietitian practitioners plus 2 employers (1 dietitian and 1 non-dietitian). The focus groups explored the key purpose, roles and outcomes of these practitioners. Data from the focus groups were confirmed with in-depth interviews about their core activities with a purposive sample of 10 individuals recently recognised as Advanced Accredited Practising Dietitians. Data from both focus groups and interviews were analysed adductively to identify key themes. Results: The key theme that emerged to define advanced dietetics practice was leadership, with four subthemes that described in more detail the major work roles and outcomes of advanced practice. These subthemes identified that advanced practitioners were (i) outcome-focused, having impact; (ii) influence others and advocate; (iii) innovate and embrace change; and (iv) inspire others and are recognised for their practice. These outcomes were conceptualised within a broad generalist framework to generate revised Competency Standards. Conclusions: This study confirmed that leadership rather than specialist practice skills is the key determinant of advanced practice

Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients

Objective:to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.Methods:We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.Results:HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10-7) outside the HLA region (65 Mb).Discussion:genetic factors predispose to the development of OCB

Biallelic loss-of-function variants in <i>CACHD1 </i>cause a novel neurodevelopmental syndrome with facial dysmorphism and multisystem congenital abnormalities

Purpose We established the genetic etiology of a syndromic neurodevelopmental condition characterized by variable cognitive impairment, recognizable facial dysmorphism, and a constellation of extra-neurological manifestations. Methods We performed phenotypic characterization of 6 participants from 4 unrelated families presenting with a neurodevelopmental syndrome and used exome sequencing to investigate the underlying genetic cause. To probe relevance to the neurodevelopmental phenotype and craniofacial dysmorphism, we established two- and three-dimensional human stem cell-derived neural models and generated a stable cachd1 zebrafish mutant on a transgenic cartilage reporter line. Results Affected individuals showed mild cognitive impairment, dysmorphism featuring oculo-auriculo abnormalities, and developmental defects involving genitourinary and digestive tracts. Exome sequencing revealed biallelic putative loss-of-function variants in CACHD1 segregating with disease in all pedigrees. RNA sequencing in CACHD1-depleted neural progenitors revealed abnormal expression of genes with key roles in Wnt signaling, neurodevelopment, and organ morphogenesis. CACHD1 depletion in neural progenitors resulted in reduced percentages of post-mitotic neurons and enlargement of 3D neurospheres. Homozygous cachd1 mutant larvae showed mandibular patterning defects mimicking human facial dysmorphism. Conclusion Our findings support the role of loss-of-function variants in CACHD1 as the cause of a rare neurodevelopmental syndrome with facial dysmorphism and multisystem abnormalities

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations

: Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) were evaluated. Patients who were FH-mutation negative had lower mean levels of pretreatment LDL-C than patients who were FH-mutation positive (217.14±55.49 versus 270.52±68.59 mg/dL, P<0.0001). The mean value (±SD) of the polygenic LDL-C risk score was 1.00 (±0.18) in patients who were FH-mutation negative and 0.94 (±0.20) in patients who were FH-mutation positive (P<0.0001). In the receiver operating characteristic analysis, the area under the curve for recognizing subjects characterized by polygenic hypercholesterolemia was 0.59 (95% CI, 0.56-0.62), with sensitivity and specificity being 78% and 36%, respectively, at 0.905 as a cutoff value. Higher mean polygenic LDL-C risk score levels were observed among patients who were FH-mutation negative having pretreatment LDL-C levels in the range of 150 to 350 mg/dL (150-249 mg/dL: 1.01 versus 0.91, P<0.0001; 250-349 mg/dL: 1.02 versus 0.95, P=0.0001). A positive correlation between polygenic LDL-C risk score and pretreatment LDL-C levels was observed among patients with FH independently of the presence of causative mutations. Conclusions This analysis confirms the role of polymorphisms in modulating LDL-C levels, even in patients with genetically confirmed FH. More data are needed to support the use of the polygenic score in routine clinical practice