Self-completed online dietary recalls as an alternative method of dietary assessment for dietetic outpatient appointments: A feasibility study

Background Integrating digital dietary assessment within dietetic care could save time and reduce costs, at the same time as increasing patient engagement. The present study explores the feasibility of implementing a web-based dietary assessment tool, myfood24 (https://www.myfood24.org), into routine healthcare. Methods This mixed methods feasibility study recruited dietitians and patients from a National Health Service (NHS) hospital outpatient setting. Patients completed and shared three online 24-h dietary recalls in advance, which were used as a dietary assessment by dietitians. Recruitment data were collected and questionnaires on technology, usability, and acceptability were completed. Patient interviews and focus groups with dietitians were conducted. Results Eleven dietitians working in allergy, bariatrics, diabetes, oncology, general, renal, infectious diseases, and coeliac services took part with 39 patients. Recruitment rates were highest in bariatrics and lowest in renal and oncology. Compared to other studies, completion rates were good, with 29 (74.4%) completing three recalls despite lower technology readiness and software usability scores than in similar studies. Illness and difficulty with technology were reasons for non-completion. Opportunity to receive nutritional feedback from the tool and share this with a dietitian motivated patients to complete the record accurately. Consultation times were shortened in approximately one-third of appointments and a higher proportion of time was spent on nutritional education compared to usual practice. However, mean preparation time increased by 13 min per appointment because dietitians found nutritional analysis reports difficult to interpret. Conclusions It is feasible to introduce a digital dietary assessment tool into NHS dietetic practice. However, further development is needed to ensure that the tool is suitable for healthcare

The Role of SINE-VNTR-Alu (SVA) Retrotransposons in Shaping the Human Genome

Retrotransposons can alter the regulation of genes both transcriptionally and post-transcriptionally, through mechanisms such as binding transcription factors and alternative splicing of transcripts. SINE-VNTR-Alu (SVA) retrotransposons are the most recently evolved class of retrotransposable elements, found solely in primates, including humans. SVAs are preferentially found at genic, high GC loci, and have been termed "mobile CpG islands". We hypothesise that the ability of SVAs to mobilise, and their non-random distribution across the genome, may result in differential regulation of certain pathways. We analysed SVA distribution patterns across the human reference genome and identified over-representation of SVAs at zinc finger gene clusters. Zinc finger proteins are able to bind to and repress SVA function through transcriptional and epigenetic mechanisms, and the interplay between SVAs and zinc fingers has been proposed as a major feature of genome evolution. We describe observations relating to the clustering patterns of both reference SVAs and polymorphic SVA insertions at zinc finger gene loci, suggesting that the evolution of this network may be ongoing in humans. Further, we propose a mechanism to direct future research and validation efforts, in which the interplay between zinc fingers and their epigenetic modulation of SVAs may regulate a network of zinc finger genes, with the potential for wider transcriptional consequences

Autosomal-dominant myopia associated to a novel P4HA2 missense variant and defective collagen hydroxylation

We recently described a complex multisystem syndrome in which mild-moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family members complaining of reduced distance vision especially at dusk underwent complete ophthalmological examination. Whole-exome sequencing was performed to identify the gene responsible for myopia in the pedigree. Moderate myopia was diagnosed in the family which was associated to the novel missense variant c.1147A > G p.(Lys383Glu) in the prolyl 4-hydroxylase,alpha-polypeptide 2 (P4HA2) gene, which catalyzes the formation of 4-hydroxyproline residues in the collagen strands. In vitro studies demonstrated P4HA2 mRNA and protein reduced expression level as well as decreased collagen hydroxylation and deposition in mutated fibroblast primary cultures compared to healthy cell lines. This study suggests that P4HA2 mutations may lead to myopic axial elongation of eyeball as a consequence of quantitative and structural alterations of collagen. This is the first confirmatory study which associates a novel dominant missense variant in P4HA2 with myopia in Caucasian patients. Further studies in larger cohorts are advisable to fully clarify genotype-phenotype correlations.We recently described a complex multisystem syndrome in which mild-moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family members complaining of reduced distance vision especially at dusk underwent complete ophthalmological examination. Whole-exome sequencing was performed to identify the gene responsible for myopia in the pedigree. Moderate myopia was diagnosed in the family which was associated to the novel missense variant c.1147A > G p.(Lys383Glu) in the prolyl 4-hydroxylase,alpha-polypeptide 2 (P4HA2) gene, which catalyzes the formation of 4-hydroxyproline residues in the collagen strands. In vitro studies demonstrated P4HA2 mRNA and protein reduced expression level as well as decreased collagen hydroxylation and deposition in mutated fibroblast primary cultures compared to healthy cell lines. This study suggests that P4HA2 mutations may lead to myopic axial elongation of eyeball as a consequence of quantitative and structural alterations of collagen. This is the first confirmatory study which associates a novel dominant missense variant in P4HA2 with myopia in Caucasian patients. Further studies in larger cohorts are advisable to fully clarify genotype-phenotype correlations

Polymerogenic neuroserpin causes mitochondrial alterations and activates NFκB but not the UPR in a neuronal model of neurodegeneration FENIB

The neurodegenerative condition FENIB (familiar encephalopathy with neuroserpin inclusion bodies) is caused by heterozygous expression of polymerogenic mutant neuroserpin (NS), with polymer deposition within the endoplasmic reticulum (ER) of neurons. We generated transgenic neural progenitor cells (NPCs) from mouse fetal cerebral cortex stably expressing either the control protein GFP or human wild type, polymerogenic G392E or truncated (delta) NS. This cellular model makes it possible to study the toxicity of polymerogenic NS in the appropriated cell type by in vitro differentiation to neurons. Our previous work showed that expression of G392E NS in differentiated NPCs induced an adaptive response through the upregulation of several genes involved in the defence against oxidative stress, and that pharmacological reduction of the antioxidant defences by drug treatments rendered G392E NS neurons more susceptible to apoptosis than control neurons. In this study, we assessed mitochondrial distribution and found a higher percentage of perinuclear localisation in G392E NS neurons, particularly in those containing polymers, a phenotype that was enhanced by glutathione chelation and rescued by antioxidant molecules. Mitochondrial membrane potential and contact sites between mitochondria and the ER were reduced in neurons expressing the G392E mutation. These alterations were associated with a pattern of ER stress that involved the ER overload response but not the unfolded protein response. Our results suggest that intracellular accumulation of NS polymers affects the interaction between the ER and mitochondria, causing mitochondrial alterations that contribute to the neuronal degeneration seen in FENIB patients

Robotic-assisted, laparoscopic, and open radical cystectomy: surgical data of 1400 patients from The Italian Radical Cystectomy Registry on intraoperative outcomes

Introduction: The Italian Radical Cystectomy Registry (Registro Italiano Cistectomie - RIC) aimed to analyse outcomes of a multicenter series of patients treated with radical cystectomy (RC) for bladder cancer. Material and methods: An observational, prospective, multicenter, cohort study was performed to collect data from RC and urinary diversion via open (ORC), laparoscopic (LRC), or robotic-assisted (RARC) techniques performed in 28 Italian Urological Departments. The enrolment was planned from January 2017 to June 2020 (goal: 1000 patients), with a total of 1425 patients included. Chi-square and t-tests were used for categorical and continuous variables. All tests were 2-sided, with a significance level set at p <0.05. Results: Overall median operative-time was longer in RARCs (390 minutes, IQR 335-465) than ORCs (250, 217-309) and LRCs (292, 228-350) (p <0.001). Lymph node dissection (LND) was performed more frequently in RARCs (97.1%) and LRCs (93.5%) than ORCs (85.6%) (p <0.001), with extended-LND performed 2-fold more frequently in RARCs (61.6%) (p <0.001). The neobladder rate was significantly higher (more than one-half) in RARCs. The median estimated blood loss (EBL) rate was lower in RARCs (250 ml, 165-400) than LRCs (330, 200-600) and ORCs (400, 250-600) (p <0.001), with intraoperative blood transfusion rates of 11.4%, 21.7% and 35.6%, respectively (p <0.001). The conversion to open rate was slightly higher in RARCs (6.8%) than LRCs (4.3%). Intraoperative complications occurred in 1.3% of cases without statistically significant differences among the approaches. Conclusions: Data from the RIC confirmed the need to collect as much data as possible in a multicenter manner. RARCs proves to be feasible with perioperative complication rates that do not differ from the other approaches

Effectiveness of a physical activity pilot intervention in youth with type 1 diabetes : the ActivPals study

Background: Type 1 Diabetes (T1D) is rising globally. Youth with T1D continue to suffer from poorer health and lower levels of physical activity (PA) than those without diabetes. The ActivPals study aimed to support young people with T1D to increase PA levels. Methods: 20 youth (aged 7-16) with T1D were randomised to a pilot PA intervention (n=10) or control group. The Actigraph GT3X+ monitor measured PA at baseline and one-month follow-up to test the effectiveness of the intervention. PedsQol scales (generic and diabetes module) were used to measure Quality of Life (QoL) in participants and parents at baseline and follow- up. Results: Changes in PA in QoL were analysed using a two- way mixed ANOVA. The results showed a significant increase in Moderate to Vigorous PA (MVPA) in both intervention and control group from baseline to follow up (p= 0.03), however there were no significant between group differences. Both groups reported significantly less overall diabetes ‘problems’ (p=0.012) and significantly less lifestyle ‘problems’ (p= 0.015) at follow up. However, intervention and control participants also reported significant increases over time in ‘problems’ with daily diabetes routine (p= 0.022). Parents reported increased worry about their child’s diabetes at follow up, significant across both groups (p= 0.046). There was no significant increase in reported hypoglycaemic occurrences despite increased MVPA. Conclusions: A larger scale trial, with longer intervention period could significantly increase the MVPA levels and QoL in youth with T1D without significantly increasing hypoglycaemic episodes

Association of Race and Ethnicity With COVID‐19 Outcomes in Rheumatic Disease: Data From the COVID‐19 Global Rheumatology Alliance Physician Registry

OBJECTIVE: Racial/ethnic minorities experience more severe outcomes of COVID-19 in the general United States (US) population. The aim of this study was to examine the association between race/ethnicity and COVID-19 hospitalization, ventilation status, and mortality in people with rheumatic disease. METHODS: US patients with rheumatic disease and COVID-19 entered into the COVID-19 Global Rheumatology Alliance physician registry March 24 - August 26, 2020 were included. Race/ethnicity was defined as white, Black, Latinx, Asian and other/mixed race. Outcomes included hospitalization, requirement for ventilatory support, and death. Multivariable regression models were used to estimate odds ratios (OR) and 95% confidence intervals controlling for age, sex, smoking, rheumatic disease diagnosis, comorbidities, medications taken prior to infection, and rheumatic disease activity. RESULTS: A total of 1,324 patients were included, of whom 36% were hospitalized and 6% died; 26% of hospitalized patients required mechanical ventilation. In multivariable models, Black (OR=2.74, 95% CI 1.90, 3.95), Latinx (OR=1.71, 95% CI 1.18, 2.49), and Asian (OR=2.69, 95% CI 1.16, 6.24) patients had higher odds of being hospitalized compared to white patients. Latinx patients also had three-fold increased odds of requiring ventilatory support (OR=3.25, 95% CI 1.75, 6.05). No differences in mortality based on race/ethnicity were found, though power may have been limited to detect associations. CONCLUSION: Similar to findings in the general US population, racial/ethnic minorities with rheumatic disease and COVID-19 had increased odds of hospitalization and ventilatory support. These results illustrate significant health disparities related to COVID-19 in people with rheumatic diseases. The rheumatology community should proactively address the needs of patients currently experiencing inequitable health outcomes during the pandemic

Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry

OBJECTIVES: To determine factors associated with COVID-19-related death in people with rheumatic diseases. METHODS: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. RESULTS: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. CONCLUSION: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants