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Background An estimated 3.5 million people in the UK live with a rare disease however due to the rarity of each individual condition this is not currently reflected in mainstream medical education. As a result, common features of living with a rare condition include diagnostic delay, poor coordination of health and social care and lack of access to specialist care and treatment. This is well documented in reports published by patient advocacy groups collating the patient experience and has been highlighted by the Department of Health and Social Care in its UK Rare Diseases Framework. One of the four priority areas outlined in this policy published in 2021 is ‘increasing awareness amongst healthcare professionals’. Medics4RareDiseases (M4RD), a charity based in the UK, has proposed a disease-agnostic approach to educating doctors about rare disease, focusing on the common challenges experienced across this heterogeneous collection of conditions, rather than on the minutiae of each of the > 7000 rare conditions. A literature search using MEDLINE, PubMed Central and Bookshelf confirmed a lack of broad rare disease teaching in medical literature; none of the 10 final resources identified focused on the topic as a whole. Results To address this, M4RD created the course ‘Rare Disease 101’. It is accessed online using a learning management system that is free, contains interactive lessons, hosts a discussion board and is easily updated. In the 29 months since going live, 942 individuals have registered with 204 having completed the course; early feedback from 33 respondents was unanimously positive (all participants rated at least good (76%: excellent)) demonstrating that both clinicians and patients can benefit from broad rare disease education. The course is freely available to all at https://learn.m4rd.org/ . Conclusions Disease-agnostic training about rare disease as a large patient population, focusing on its unique profile of unmet needs, is required. Rare Disease 101 provides a pragmatic approach to an educational challenge that leads to poor patient outcomes. Early results suggest that the educational programme is well-received but further evaluation and assessment is needed.

Auditory verbal hallucinations (AVH) often lead to distress and functional disability, and are frequently associated with psychotic illness. Previously both state and trait magnetic resonance imaging (MRI) studies of AVH have identified activity in brain regions involving auditory processing, language, memory and areas of default mode network (DMN) and salience network (SN). Current evidence is clouded by research mainly in participants on long-term medication, with chronic illness and by choice of seed regions made ‘a priori’. Thus, the aim of this study was to elucidate the intrinsic functional connectivity in patients presenting with first episode psychosis (FEP). Resting state functional MRI data were available from 18 FEP patients, 9 of whom also experienced AVH of sufficient duration in the scanner and had symptom capture functional MRI (sc fMRI), together with 18 healthy controls. Symptom capture results were used to accurately identify specific brain regions active during AVH; including the superior temporal cortex, insula, precuneus, posterior cingulate and parahippocampal complex. Using these as seed regions, patients with FEP and AVH showed increased resting sb-FC between parts of the SN and the DMN and between the SN and the cerebellum, but reduced sb-FC between the claustrum and the insula, compared to healthy controls.It is possible that aberrant activity within the DMN and SN complex may be directly linked to impaired salience appraisal of internal activity and AVH generation. Furthermore, decreased intrinsic functional connectivity between the claustrum and the insula may lead to compensatory over activity in parts of the auditory network including areas involved in DMN, auditory processing, language and memory, potentially related to the complex and individual content of AVH when they occur.

Over one billion people live with disability worldwide, of whom 80% are in developing countries. Robust childhood disability data are limited, particularly as tools for identifying disability function poorly at young ages. A subgroup of children enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (a cluster-randomised, community-based, 2x2 factorial trial in two rural districts in Zimbabwe) had neurodevelopmental assessments at 2 years of age. We evaluated functional difficulty prevalence in HIV-exposed and HIV-unexposed children using the Washington Group Child Functioning Module (WGCFM), comparing absolute difference using chi-squared or Fisher's exact tests. Concurrent validity with the Malawi Developmental Assessment Tool (MDAT) was assessed using logistic regression with cohort MDAT score quartiles, linear regression for unit-increase in raw scores and a Generalised Estimating Equation approach (to adjust for clusters) to compare MDAT scores of those with and without functional difficulty. A 3-step, cluster-adjusted multivariable regression model was then carried out to examine risk factors for functional difficulty. Functional Difficulty prevalence was 4.2% (95%CI: 3.2%, 5.2%) in HIV-unexposed children (n = 1606) versus 6.1% (95%CI: 3.5%, 8.9%) in HIV-exposed children (n = 314) (absolute difference 1.9%, 95%CI: -0.93%, 4.69%; p = 0.14). Functional difficulty score correlated negatively with MDAT: for each unit increase in WGCFM score, children completed 2.6 (95%CI: 2.2, 3.1) fewer MDAT items (p = 0.001). Children from families with food insecurity and poorer housing were more at risk of functional difficulty. Functional difficulty was identified in approximately 1-in-20 children in rural Zimbabwe, which is comparable to prevalence in previous studies. WGCFM showed concurrent validity with the MDAT, supporting its use in early childhood.

Glycogen storage disease type 1 (GSD-1) is a group of inherited metabolic disorders characterised by the inability to use intracellular glucose stores. It is associated with a high risk of hypoglycaemia, as well as long-term complications including growth retardation, hepatocellular adenomas, renal disease, hypertriglyceridaemia and hyperuricaemia. Treatment involves slow absorption carbohydrates, for example, cornstarch. We present a case of acute psychosis in a patient with GSD-1a. This was initially attributed to his opiate use. Later in his management an MRI scan of his head was performed which revealed regions of brain atrophy following significant hypoglycaemic insult, thus identifying an organic cause of his psychosis. This case presents a rare complication of glycogen storage disease: organic psychosis attributable to cortical atrophy from profound hypoglycaemic insult. It emphasises the importance of investigating organic causes of psychiatric symptoms.

IntroductionOur objective was to describe the population of infants <7 days of age admitted to the acute general paediatric services at Alder Hey Children’s Hospital and ascertain the proportion with feeding difficulties amenable to community-based support.MethodsSequential retrospective audits of all infants <7 days of age admitted to acute paediatrics at Alder Hey Children’s Hospital, Liverpool, England, from March to September 2019 (pre-COVID-19) and March to September 2020 (during COVID-19). All the infants were born and discharged from maternity units in Merseyside, Northwest England. Anonymised data were extracted from the electronic clinical records by three members of the clinical team.ResultsPre-COVID-19, 38.6% (93) of the 241 admissions to acute general paediatric services had feeding difficulties. 31.2% (29) presented solely with feeding difficulties and 31.2% (29) were exclusively breastfed. However, during COVID-19, although there were fewer admissions (104), more than half (51%, 54) had feeding difficulties and for 54% (29), this was the only reason for admission. Over half (53.7%, 29) were exclusively breastfed.ConclusionOur audits showed that at least a third of infants <7 days of age admitted with feeding difficulties did not have any other features of severe illness. These admissions unnecessarily expose infants to hospital-acquired infections while disrupting the opportunity for families to build close and loving relationships that enhance the establishment of breastfeeding. Co-designing infant feeding strategies with the mothers and stakeholders will be a crucial next step to enhance infant feeding support, particularly in impoverished communities in the region.

Abstract Background Auditory verbal hallucinations (AVH) often lead to distress and functional disability, and are frequently associated with psychotic illness. Theories of abnormal integration have been proposed to explain symptoms of schizophrenia, including delusions and hallucinations, with a central abnormality being aberrant activity in intrinsic brain networks such as the default mode network (DMN) or the salience network (SN). Previous investigations of patients with schizophrenia assessing functional connectivity (FC) have used a seed-based functional connectivity approach (sb-FC), with seed placement in brain areas responsible for auditory processing, language, and memory; the striatum, and in areas of DMN. These have generated some conflicting results, possibly because of the varying seed placement. The aim of the current study was to address these confounding factors by investigating the intrinsic FC in first episode psychosis (FEP) patients with AVH using within-sample AVH symptom capture seeds. It was hypothesised that patients would show aberrant resting state FC between areas of the DMN and SN and these areas. Methods Eighteen FEP individuals and 20 healthy controls were recruited. All the participants underwent resting-state functional Magnetic Resonance Imaging (rs-fMRI). The Data Processing Assistant for Resting-State fMRI Advanced Edition (DPARSFA) V3.1 (http://rfmri.org/DPARSF) (Yan & Zang, 2010) and the statistical parametric mapping software 8 (SPM8) (SPM, Friston, The Wellcome Department of Cognitive Neurology, London, Uk; http://www.fil.ion.ucl.ac.uk/spm) were used to preprocess and analyze the data. Results Patients showed increased FC between left insula and bilateral cerebellum, and angular gyrus; and increased FC between left claustrum and left cerebellum and postcentral gyrus. There was reduced FC in FEP patients with AVH between left claustrum and left insula compared to HC. The FC between left insula and left claustrum seeds for patients and HC is shown separately in supplementary information. There were no significant correlations between DUP, dose of antipsychotic medications, and severity of hallucinations and the mean coefficients of clusters that were significantly different between FEP patients and HC. Discussion FEP patients showed increased functional connectivity between left insula and bilateral cerebellum and angular gyrus; and increased functional connectivity between left claustrum and left cerebellum and postcentral gyrus. We also found reduced functional connectivity between left claustrum and left insula in FEP patients compared to HC. It is possible the pathology of AVH is primarily located in the insula and angular gyrus. However, given our results of both the left insula seed in patients and HC shows connectivity with right insula and anterior cingulate cortex (key regions of SN) and literature from patients with chronic AVH, the suggestion may be that resting state dysconnectivity within the DMN and SN are implicated in the generation of AVH, which during the experience itself will further involve temporal and auditory networks. Furthermore, decreased intrinsic functional connectivity between the claustrum and the insula may lead to compensatory over activity in parts of the auditory network including areas involved in DMN, auditory processing, language and memory, leading to the complex and individual content of AVH when they occur.

Of the estimated 1.4 million salmonella infections that occur each year in the United States, most are in children and the elderly and approximately 600 are fatal. 1 Septicemia complicates at least 7 percent of the 40,000 culture-confirmed infections that are reported each year. 1 , 2 Although antibiotics are not essential for the treatment of most cases of salmonellosis, they can be lifesaving in persons with invasive disease. Expanded-spectrum cephalosporins (e.g., ceftriaxone) are commonly used to treat salmonella infections in children because of their pharmacodynamic properties and the very low prevalence of resistance to these agents. Since 1991, salmonella species that are . . .

Graphical probabilistic models have the ability to provide insights as to how clinical factors are conditionally related. These models can be used to help us understand factors influencing health care outcomes and resource utilization, and to estimate morbidity and clinical outcomes in trauma patient populations. Thirty-two combat casualties with severe extremity injuries enrolled in a prospective observational study were analyzed using step-wise machine-learned Bayesian belief network (BBN) and step-wise logistic regression (LR). Models were evaluated using 10-fold cross-validation to calculate area-under-the-curve (AUC) from receiver operating characteristics (ROC) curves. Our BBN showed important associations between various factors in our data set that could not be developed using standard regression methods. Cross-validated ROC curve analysis showed that our BBN model was a robust representation of our data domain and that LR models trained on these findings were also robust: hospital-acquired infection (AUC: LR, 0.81; BBN, 0.79), intensive care unit length of stay (AUC: LR, 0.97; BBN, 0.81), and wound healing (AUC: LR, 0.91; BBN, 0.72) showed strong AUC. A BBN model can effectively represent clinical outcomes and biomarkers in patients hospitalized after severe wounding, and is confirmed by 10-fold cross-validation and further confirmed through logistic regression modeling. The method warrants further development and independent validation in other, more diverse patient populations.