Abstract In the UK, for patients with inherited metabolic disorders (IMD) the traditional system for acquiring essential dietary products [patient prompted prescriptions generated by a medical general practitioner (GP) and dispensed by a chemist] is problematic. Objective To investigate the efficacy of a home delivery service (HDS) for essential dietary products (EDP) (i.e. protein substitutes, milk replacements, energy and vitamin and mineral supplements) for subjects with IMD, particularly examining any prescription and dispensing errors, metabolic control and consumer satisfaction. Methods A prospective, controlled, home delivery trial for EDP was conducted in patients with IMD for 12 months. Sixty‐two patients with IMD [50 with phenylketonuria (PKU); 12 with other IMD: aged 6 months–30 years] were recruited. Thirty subjects used a monthly HDS (Homeward: Nutricia) to receive EDP, 32 remained on the traditional system. Each month, the HDS checked home stock levels of EDP, obtained their prescriptions directly from GP's, and then delivered them to the subjects’ homes. An independent researcher completed monthly telephone interviews with patients/parents about any EDP prescription errors or delay in receipt. Results Incorrect protein substitute was dispensed once by the HDS compared with nine subjects who had 12 errors in the control group ( P = 0.01); incorrect flavours of protein substitute were dispensed to the home delivery group once compared with eight subjects getting 11 errors via the chemist ( P = 0.03). The HDS delayed delivery of protein substitute for one subject on three occasions compared with 39 occasions in 16 subjects via the chemist ( P = 0.001). In patients with PKU, plasma phenylalanine control deteriorated in the control group ( P < 0.05) but not in the HDS group. Conclusions The long‐term use of a HDS for EDP in IMD is safer, effective and more reliable than conventional systems.
Papillary thyroid carcinoma, is the commonest histologic subtype of thyroid malignancies .It is also renowned for its best prognosis.Invasion of aero digestive tract is commoner with the anaplastic histologic variant.This invasion leads to obstructive (dysphagia) or erosive(hematemesis) symptoms commonly. Invasion of aero digestive tract by well differentiated thyroid cancer presenting with anemia is one of the rarest occurrence. We, report a case of 68 year old female presented with features of iron deficiency anemia and stool Occult Blood Test positive. On further evaluation was observed to have an esophageal growth, which when biopsied was confirmed as papillary carcinoma of thyroid gland.
Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015-22 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0 - 9.6) and 4.0 (1.8 - &gt;70) µmol/L respectively and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C, in ‘asymptomatic’ individuals (n=17), demonstrating a median (range) C5C of 3.0 (1.8 – 7.1) whilst ‘clinically affected’ patients (n=7), showed a median (range) C5C of 13.9 (7.7 - &gt; 70) µmol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 µmol/L triggering urgent referral, and those &gt; 2.0 and &lt; 5.0 µmol/L prompting 2nd tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder.
Infusion related reactions (IRRs) in patients receiving enzyme replacement therapies (ERTs) for lysosomal storage disorders are well recognised, with mild reactions reported in 15%– 50% of patients, and severe or anaphylactic reactions in 0.2%–7.7%. Acute assessment, investigation and management practices vary. This study aimed to review practice in a tertiary centre and to optimise assessment and management pathways.
Methods
A single-centre 4 year retrospective case-note review was undertaken. All patients receiving ERT were included, and the IRR incidence determined. Acute assessment, investigations and management were compared with current anaphylaxis guidelines (Resuscitation Council UK; Royal College of Paediatrics and Child Health).
Results v
105 patients receiving ERT were identified (idursulfase n=21; alglucosidase alfa n=15; laronidase n=15; elosulfase alfa n=14; velaglucerase n=14, galsulfase n=9; agalsidase alpha n=9; agalsidase beta n=4; imiglucerase n=4). 5 (4.8%) had significant (moderate or severe) IRRs (laronidase n=2, idursulfase n=1, elosulfase n=1, agalsidase beta n=1). 4 (80%) were male and the mean age at first IRR was 6.7 years (range 3.6–12.2). IRRs occurred on 5–8th infusion (n=4) and 25th infusion (n=1), and at varying rate increments. Only 60% of mandated clinical assessments were documented. 3/5 were classified as having anaphylaxis and 2/5 moderate hypersensitivity reactions. Investigations obtained included: tryptase (performed in 5/5; all 5 normal); total IgE (performed in 3/5, 2 abnormal); anti-ERT IgG antibody (performed in 5/5, titres 800– 51 200). Acute management included pausing infusion (5/5); additionally 2/5 received intravenous hydrocortisone only, and 3 received intramuscular adrenaline, intravenous hydrocortisone and intravenous antihistamine. 80% received treatment appropriate for the IRR severity classification.Subsequent management included addition of steroid pre-medication (5/5) and infusion rate modification (3/5). All could successfully continue treatment.
Conclusions
The occurrence of severe anaphylaxis to ERT warrants in-hospital initiation of ERT. A standardised 'Traffic Light' ERT reaction protocol (green – mild reaction; yellow – moderate hypersensitivity; red – severe anaphylaxis ) has been developed to facilitate optimum nursing and medical assessment, investigation and management of IRRs.
Abstract Objectives This UK‐wide study defines the natural history of argininosuccinic aciduria and compares long‐term neurological outcomes in patients presenting clinically or treated prospectively from birth with ammonia‐lowering drugs. Methods Retrospective analysis of medical records prior to March 2013, then prospective analysis until December 2015. Blinded review of brain MRIs. ASL genotyping. Results Fifty‐six patients were defined as early‐onset ( n = 23) if symptomatic < 28 days of age, late‐onset ( n = 23) if symptomatic later, or selectively screened perinatally due to a familial proband ( n = 10). The median follow‐up was 12.4 years (range 0–53). Long‐term outcomes in all groups showed a similar neurological phenotype including developmental delay (48/52), epilepsy (24/52), ataxia (9/52), myopathy‐like symptoms (6/52) and abnormal neuroimaging (12/21). Neuroimaging findings included parenchymal infarcts (4/21), focal white matter hyperintensity (4/21), cortical or cerebral atrophy (4/21), nodular heterotopia (2/21) and reduced creatine levels in white matter (4/4). 4/21 adult patients went to mainstream school without the need of additional educational support and 1/21 lives independently. Early‐onset patients had more severe involvement of visceral organs including liver, kidney and gut. All early‐onset and half of late‐onset patients presented with hyperammonaemia. Screened patients had normal ammonia at birth and received treatment preventing severe hyperammonaemia. ASL was sequenced ( n = 19) and 20 mutations were found. Plasma argininosuccinate was higher in early‐onset compared to late‐onset patients. Conclusions Our study further defines the natural history of argininosuccinic aciduria and genotype–phenotype correlations. The neurological phenotype does not correlate with the severity of hyperammonaemia and plasma argininosuccinic acid levels. The disturbance in nitric oxide synthesis may be a contributor to the neurological disease. Clinical trials providing nitric oxide to the brain merit consideration.
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