Optimising the management of bone disease for coeliac patients in a dietetic-led clinic

Coeliac disease (CD) is a chronic autoimmune inflammatory condition of the small bowel; the only treatment is lifelong adherence to a gluten free diet (GFD). Adherence to a GFD also minimises the risk of associated conditions such as osteoporosis in CD patients. The present study aimed to evaluate and optimise management of bone disease in CD patients in a dietetic-led clinic. This study was conducted in two parts: study 1 utilised retrospective data to evaluate management of bone disease with reference to British Society of Gastroenterology (BSG) guidelines in 229 CD patients. Based on the results from study 1, study 2 developed a tool to estimate dietary calcium intake in CD patients, which was then trialled on 50 patients. There were no significant differences between the population demographics for study 1 and study 2. 65% of patients had a diagnosis of osteopenia or osteoporosis, in a female predominant population (74.6%). Reported mean dietary calcium intake was over estimated at 1239.6mg/day (SD ± 377.1mg) in study 1 and corrected to 852mg/day (SD ± 264.57mg) using improved methodology (study 2) (p≤0.05). Understanding and compliance with dietary advice correlated positively with GFD (p≤0.001) but not osteoporosis or fracture risk. Overall patients attending the clinic did not meet the BSG recommended calcium intake. However, 30% of patients could meet the 2014 BSG target from oral diet alone. Utilising individual dietary prescriptions and targeted use of calcium supplementation maximised the opportunity to reduce risk of bone disease and improved compliance with BSG recommendations.http://pubs.sciepub.com/ijcd/4/2/6

Local lung responses following endobronchial elastase and lipopolysaccharide instillation in sheep

Chronic lipopolysaccharide (LPS) exposure may contribute to the pathogenesis of a number of lung diseases including COPD and emphysema. We sought to develop a large- animal model of emphysema using repeated LPS administration into sheep lung segments. An experimental protocol was designed to facilitate comparisons with elastase-treated and control segments within the same lung of individual sheep. Histopathologic evaluation of segments treated with LPS demonstrated low-grade inflammation characterized by an increase in the number of intra-alveolar macrophages and lymphocytes. Treated segments demonstrated a significant reduction in airspace surface area (ASA), an increase in percent disrupted alveolar attachments and the distance between normal alveolar attachments, and a reduction in the number of normal alveolar attachments surrounding nonrespiratory bronchioles. Coefficient of variation of individual ASA measurements in elastase-treated segments was indicative of a heterogeneous parenchymal response, in contrast to that associated with chronic LPS treatment. Our results demonstrate that chronic LPS treatment of individual lung segments in sheep induces microscopic emphysema qualitatively and quantitatively consistent with both accepted pathologic definitions of this condition and with that produced by airway instillation of elastolytic enzymes. Development of this phenotype is associated with evidence of downregulated activation of transforming growth factor beta

Diagnostic and Management Issues in Patients with Late-Onset Ornithine Transcarbamylase Deficiency

Ornithine transcarbamylase deficiency (OTCD) is the most common inherited disorder of the urea cycle and, in general, is transmitted as an X-linked recessive trait. Defects in the OTC gene cause an impairment in ureagenesis, resulting in hyperammonemia, which is a direct cause of brain damage and death. Patients with late-onset OTCD can develop symptoms from infancy to later childhood, adolescence or adulthood. Clinical manifestations of adults with OTCD vary in acuity. Clinical symptoms can be aggravated by metabolic stressors or the presence of a catabolic state, or due to increased demands upon the urea. A prompt diagnosis and relevant biochemical and genetic investigations allow the rapid introduction of the right treatment and prevent long-term complications and mortality. This narrative review outlines challenges in diagnosing and managing patients with late-onset OTCD

Special Low Protein Foods Prescribed in England for PKU Patients: An Analysis of Prescribing Patterns and Cost.

Patients with phenylketonuria (PKU) are reliant on special low protein foods (SLPFs) as part of their dietary treatment. In England, several issues regarding the accessibility of SLPFs through the national prescribing system have been highlighted. Therefore, prescribing patterns and expenditure on all SLPFs available on prescription in England (n = 142) were examined. Their costs in comparison to regular protein-containing (n = 182) and 'free-from' products (n = 135) were also analysed. Similar foods were grouped into subgroups (n = 40). The number of units and costs of SLPFs prescribed in total and per subgroup from January to December 2020 were calculated using National Health Service (NHS) Business Service Authority (NHSBSA) ePACT2 (electronic Prescribing Analysis and Cost Tool) for England. Monthly patient SLPF units prescribed were calculated using patient numbers with PKU and non-PKU inherited metabolic disorders (IMD) consuming SLPFs. This was compared to the National Society for PKU (NSPKU) prescribing guidance. Ninety-eight percent of SLPF subgroups (n = 39/40) were more expensive than regular and 'free-from' food subgroups. However, costs to prescribe SLPFs are significantly less than theoretical calculations. From January to December 2020, 208,932 units of SLPFs were prescribed (excluding milk replacers), costing the NHS £2,151,973 (including milk replacers). This equates to £962 per patient annually, and prescribed amounts are well below the upper limits suggested by the NSPKU, indicating under prescribing of SLPFs. It is recommended that a simpler and improved system should be implemented. Ideally, specialist metabolic dietitians should have responsibility for prescribing SLPFs. This would ensure that patients with PKU have the necessary access to their essential dietary treatment, which, in turn, should help promote dietary adherence and improve metabolic control

Diagnostic and Management Issues in Patients with Late-Onset Ornithine Transcarbamylase Deficiency

Ornithine transcarbamylase deficiency (OTCD) is the most common inherited disorder of the urea cycle and, in general, is transmitted as an X-linked recessive trait. Defects in the OTC gene cause an impairment in ureagenesis, resulting in hyperammonemia, which is a direct cause of brain damage and death. Patients with late-onset OTCD can develop symptoms from infancy to later childhood, adolescence or adulthood. Clinical manifestations of adults with OTCD vary in acuity. Clinical symptoms can be aggravated by metabolic stressors or the presence of a catabolic state, or due to increased demands upon the urea. A prompt diagnosis and relevant biochemical and genetic investigations allow the rapid introduction of the right treatment and prevent long-term complications and mortality. This narrative review outlines challenges in diagnosing and managing patients with late-onset OTCD

Dietetic Management of Adults with Phenylketonuria (PKU) in the UK: A Care Consensus Document.

There is an increasing number of adults and elderly patients with phenylketonuria (PKU) who are either early, late treated, or untreated. The principal treatment is a phenylalanine-restricted diet. There is no established UK training for dietitians who work with adults within the specialty of Inherited Metabolic Disorders (IMDs), including PKU. To address this, a group of experienced dietitians specializing in IMDs created a standard operating procedure (SOP) on the dietetic management of adults with PKU to promote equity of care in IMD dietetic services and to support service provision across the UK. The group met virtually over a period of 12 months until they reached 100% consensus on the SOP content. Areas of limited evidence included optimal blood phenylalanine reporting times to patients, protein requirements in older adults, management of weight and obesity, and management of disordered eating and eating disorders. The SOP does not include guidance on maternal PKU management. The SOP can be used as a tool for training dietitians new to the specialty and to raise the standard of education and care for patients with PKU in the UK

The role of coping in the association between subclinical psychotic experiences and daily functioning: evidence from two independent adolescent samples from the general population

An inverse association between psychosocial functioning and psychotic experiences is now established in both clinical and non-clinical populations, however the mechanisms which drive this are unclear. Adolescents with subclinical psychotic experiences (SPE) are more likely to use maladaptive coping strategies and less likely to use adaptive ones, and maladaptive coping has also been associated with poor functioning. A within study replication in two adolescent samples from the general populations of Melbourne, Australia (n = 723) and Birmingham, United Kingdom (n = 239), was conducted to determine whether the association between SPE and psychosocial functioning is mediated by coping style. SPE were associated with reduced general and family functioning and to a lesser extent with reduced peer functioning. Task-oriented (focusing on solving the problem) and emotion-oriented (negative emotional responses) coping were found to mediate the relationship between SPE and three types of functioning in both the Melbourne and the Birmingham samples. The within study replication consistently found that coping style mediates SPE and psychosocial functioning, despite significant differences in age, gender, functioning, use of coping styles, and level of SPE between the two samples. Longitudinal research is needed to fully understand any causal role coping may play in the relationship between SPE and poor functioning. The results have important public health and clinical implications, and suggest that techniques which increase levels of adaptive coping and reduce levels of maladaptive coping (in particular emotion-oriented styles) may help to break the cycle between SPE, functional decline, and eventual need for care

Clinical, biochemical and molecular analysis in a cohort of individuals with gyrate atrophy

Abstract Background Gyrate atrophy of the choroid and retina is a rare autosomal recessive metabolic disorder caused by biallelic variants in the OAT gene, encoding the enzyme ornithine δ-aminotransferase. Impaired enzymatic activity leads to systemic hyperornithinaemia, which in turn underlies progressive chorioretinal degeneration. In this study, we describe the clinical and molecular findings in a cohort of individuals with gyrate atrophy. Methods Study participants were recruited through a tertiary UK clinical ophthalmic genetic service. All cases had a biochemical and molecular diagnosis of gyrate atrophy. Retrospective phenotypic and biochemical data were collected using electronic healthcare records. Results 18 affected individuals from 12 families (8 male, 10 female) met the study inclusion criteria. The median age at diagnosis was 8 years (range 10 months – 33 years) and all cases had hyperornithinaemia (median: 800 micromoles/L; range: 458–1244 micromoles/L). Common features at presentation included high myopia (10/18) and nyctalopia (5/18). Ophthalmic findings were present in all study participants who were above the age of 6 years. One third of patients had co-existing macular oedema and two thirds developed pre-senile cataracts. Compliance with dietary modifications was suboptimal in most cases. A subset of participants had extraocular features including a trend towards reduced fat-free mass and developmental delay. Conclusions Our findings highlight the importance of multidisciplinary care in families with gyrate atrophy. Secondary ophthalmic complications such as macular oedema and cataract formation are common. Management of affected individuals remains challenging due to the highly restrictive nature of the recommended diet and the limited evidence-base for current strategies