Meconium Ileus in Two Irish Newborns: The Presenting Feature of Cystic Fibrosis

Introduction Meconium Ileus (MI) is the presenting feature of CF in approximately 10-15% of cases. This report outlines the clinical presentation, imaging and management of two neonates with MI and subsequent diagnosis of Cystic Fibrosis (CF). Methods A retrospective chart review was performed to evaluate the clinical course of two neonates with MI. Results Case 1 and 2 presented clinically with signs of abdominal obstruction. Subsequent laparotomies confirmed MI. MI is strongly associated with CF and CF is the most common genetically inherited disease in Ireland. Genetic testing was positive for a homozygous ∆ F508 mutation in both case 1 and 2, securing a diagnosis of MI secondary to CF. Conclusion Our cases highlight that all infants born in Ireland with MI should be considered as CF positive until proven otherwise.

Reversal of warfarin anticoagulation using prothrombin complex concentrate at 25 IU kg-1 : results of the RAPID study.

BACKGROUND: Real-world studies of the emergency reversal of warfarin using 4-factor prothrombin complex concentrate (PCC) report unwarranted delays. The delay to receiving PCC was ≥ 8 h in 46·7% of patients with warfarin-associated bleeding (PWAB) treated with a variable PCC dosing protocol in our retrospective audit. OBJECTIVE: To report the impact of a simplified PCC dosing protocol on the interval to reversal of anticoagulation. METHODS: We developed a PCC dosing protocol standardising the initial PCC dose and simplifying dosing calculations. Study end points were the proportion of PWAB achieving international normalised ratio (INR) ≤1·5 and treated within 8 h of presentation, respectively. RESULTS: Of 17, 15 (88·2%) PWABs achieved a post-treatment INR ≤ 1·5; 14 of 17 (82·4%) PWABs were reversed within 8 h. Median intervals between triage and PCC request and PCC request and start of infusion (administration interval) were 126 min (range 39-520) and 30 min (range 5-100), respectively. Compared with the retrospective cohort, RAPID is associated with an improved administration interval (mean 37·7 vs 76 min, P = 0·031) and the proportion of PWABs treated within 30 min (58·8 vs 6·7%, P = 0·009). CONCLUSION: The RAPID protocol reduces unwarranted delays without compromising efficacy.

Clinical and biochemical phenotypes of adults with monoallelic and biallelic CYP24A1 mutations: evidence of gene dose effect.

UNLABELLED: Mutations of the CYP24A1 gene can result in hypercalcemia, hyerpercalciuria, and nephrolithiasis, but disease severity is variable. Clinical and biochemical phenotypes were correlated with gene sequence information in a family with two CYP24A1 mutations. A gene dose effect was apparent with monoallelic mutations demonstrating milder disease manifestations than biallelic mutations. INTRODUCTION: The objective was to examine the spectrum of clinical and biochemical phenotypes in a family with monoallelic and biallelic mutations of CYP24A1 after identification of the proband with two mutations of the CYP24A1 gene: (A) p.R396W and (B) E143del-Het. METHODS: Clinical and biochemical phenotypes were correlated with CYP24A1 sequence information in the proband and four siblings, a daughter, and two nieces of the proband. The subjects' medical histories were evaluated, and measurement of serum minerals, vitamin D metabolites, PTH, bone turnover markers, and urinary calcium and sequencing of the CYP24A1 gene were performed. RESULTS: The proband had nephrolithiasis, osteopenia, hypercalcemia, hypercalciuria, elevated serum 1,25(OH)2D, undetectable 24,25(OH)2D, and inappropriately low PTH concentrations. Two subjects with biallelic (A/B) mutations had nephrolithiasis, marked hypercalciuria (583 ± 127 mg/24 h, mean ± SD), compared with five subjects with monoallelic mutations (A or B) with a urine calcium of 265 ± 85 mg/24 h. Two subjects with monoallelic mutations had nephrolithiasis and one had non-PTH dependent hypercalcemia. Five subjects had high 1,25(OH)2D measurements, including three with monoallelic mutations. The 25OHD/24,25(OH)2D ratio, in subjects with biallelic mutations was 291 versus 19.8 in the subjects with monoallelic mutations. CONCLUSIONS: In this family, adults with CYP24A1 mutations a gene dose effect is apparent: subjects with biallelic, compound heterozygous mutations (A/B) have a more severe clinical and biochemical phenotype, whereas, subjects with monoallelic mutations demonstrate milder disease manifestations which are not easily characterized through biochemical assessment.

Nuchal Translucency Quality Review (NTQR) program: first one and half million results.

OBJECTIVE: To evaluate the performance of first-trimester nuchal translucency (NT) measurement by providers (physician-sonologists and sonographers) within the Nuchal Translucency Quality Review (NTQR) program. METHODS: After training and credentialing providers, the NTQR monitored performance of NT measurement by the extent to which an individual's median multiple of the normal median (MoM) for crown-rump length (CRL) was within the range 0.9-1.1 MoM of a published normal median curve. The SD of log10 MoM and regression slope of NT on CRL were also evaluated. We report the distribution between providers of these performance indicators and evaluate potential sources of variation. RESULTS: Among the first 1.5 million scans in the NTQR program, performed between 2005 and 2011, there were 1 485 944 with CRL in the range 41-84 mm, from 4710 providers at 2150 ultrasound units. Among the 3463 providers with at least 30 scans in total, the median of the providers' median NT-MoMs was 0.913. Only 1901 (55%) had a median NT-MoM within the expected range; there were 89 above 1.1 MoM, 1046 at 0.8-0.9 MoM, 344 at 0.7-0.8 MoM and 83 below 0.7 MoM. There was a small increase in the median NT-MoM according to providers' length of time in the NTQR program and number of scans entered annually. On average, physician-sonologists had a higher median NT-MoM than did sonographers, as did those already credentialed before joining the program. The median provider SD was 0.093 and the median slope was 13.5%. SD correlated negatively with the median NT-MoM (r = -0.34) and positively with the slope (r = 0.22). CONCLUSION: Even with extensive training, credentialing and monitoring, there remains considerable variability between NT providers. There was a general tendency towards under-measurement of NT compared with expected values, although more experienced providers had performance closer to that expected.

Inflammatory bowel disease and thromboembolism. Is inflammation at the centre of the clot?

Thromboembolic events are well recognised in patients with inflammatory bowel disease (IBD). We present three cases which highlight the need for vigilance with respect to this complication. We also propose that consideration be given to re-evaluating disease activity in those patients who develop thromboembolic complications.

A qualitative evaluation of a telehealth healthy lifestyle intervention for people with serious mental illness.

OBJECTIVES: There are high levels of nutritional and metabolic, cardiovascular, and respiratory tract diseases among people diagnosed with serious mental illness (SMI). Consequently, we developed a pragmatic, affordable nutritional and exercise intervention: Choices4Health. Due to the COVID-19 pandemic, we modified this intervention so it could be delivered online. The aim of this study was to explore the experience of participating in online Choices4Health, in a real-world clinical setting, from the perspectives of service users with SMI. METHODS: The study aim was addressed using thematic analysis. Service users who had attended online Choices4Health, received a SMI diagnosis (defined as a schizophrenia spectrum disorder or an affective disorder), and resided in a South Dublin catchment were invited to participate. Nine participants were purposefully sampled. Semi-structured interviews were conducted by telephone. Data analysis was guided by thematic analysis procedures. RESULTS: Six themes were generated: Being ready and not overburdened (Engagement); Gaining knowledge and implementing it (Learning and doing); Viewing the intervention as appropriate and effective (Targeted impact); Being at home with others online (Belonging); Having a positive affective attitude towards the intervention (Feeling); and Perceiving problems with intervention delivery (Recommended change). CONCLUSIONS: Findings suggest that online Choices4Health is, broadly speaking, acceptable from a service user perspective, but that further refinement is required to address specific issues participants identified. These relate to follow-up or programme extension, technology access, in-person contact preference, and participant inclusion criteria. Further research is required into online Choices4Health efficacy, innovations to reduce digital exclusion, and managing group dynamics in telehealth interventions.

Is it feasible to use a humanoid robot to promote hand hygiene adherence in a hospital setting?

Healthcare associated infections (HCAI) are a prevalent preventable cause of morbidity and mortality. Improving hand hygiene adherence is important for HCAI prevention. In this feasibility study, the objective was to determine if a humanoid robot could act as a novel single reminder intervention to improve hand hygiene adherence in a hospital setting. DAVE, a social humanoid robot, improved hand hygiene adherence at the entrance to a tertiary hospital and outpatient department, which was low at baseline, by 29%. DAVE shows promise as a novel intervention to improve hand hygiene adherence.

A quick, least-invasive, inexpensive and reliable method for sampling Gadus morhua postlarvae for genetic analysis.

The present study describes the successful design and testing of a quick, least-invasive, reliable and inexpensive sampling procedure for Atlantic cod Gadus morhua. This protocol can be easily applied to postlarval fish following a simple three-step procedure, without availing of commercial DNA extraction kits, while ensuring survival of sampled individuals.

Vaccine-induced thrombosis and thrombocytopenia (VITT) in Ireland: A review of cases and current practices.

Since the beginning of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) virus pandemic, several highly effective and safe vaccines have been produced at remarkable speed. Following global implementation of vaccination programmes, cases of thrombosis with thrombocytopenia following administration of adenoviral vector-based vaccines started being reported. In this review we discuss the known pathogenesis and epidemiology of so-called vaccine induced thrombocytopenia and thrombosis (VITT). We consider the available guidelines, diagnostic laboratory tests and management options for these patients. Finally, we discuss important unanswered questions and areas for future research in this novel pathoclinical entity.

Effect of walking speed changes on tibialis anterior EMG during healthy gait for FES envelope design in drop foot correction.

Functional electrical stimulation may be used to correct hemiplegic drop foot. An optimised stimulation envelope to reproduce the EMG pattern observed in the tibialis anterior (TA) during healthy gait has been proposed by O'Keeffe et al. [O'Keeffe, D.T., Donnelly, A.E., Lyons, G.M., 2003. The development of a potential optimised stimulation intensity envelope for drop foot applications. IEEE Transactions on Neural Systems and Rehabilitation Engineering]. However this envelope did not attempt to account for changes in TA activity with walking speed. The objective of this paper was to provide data to enable the specification of an algorithm to control the adaptation of an envelope with walking speed. Ten young healthy subjects walked on a treadmill at 11 different walking speeds while TA EMG was recorded. The results showed that TA EMG recorded around initial contact and at toe off changed with walking speed. At the slowest velocities, equivalent to hemiplegic walking, the toe-off burst (TOB) of EMG activity had larger peak amplitude than that of the heel-strike burst (HSB). The peak amplitude ratio of TOB:HSB was 1:0.69 at the slowest speed compared to, 1:1.18 and 1:1.5 for the self-selected and fastest speed, respectively. These results suggest that an FES envelope, which produces larger EMG amplitude for the TOB than the HSB, would be more appropriate at walking speeds typical of hemiplegic patients.

The application of a use case/task based approach in the development of software for a portable neuromuscular stimulator device.

This paper describes the use of a use case/task based method in the development of a portable neuromuscular stimulator device. The developed unit allows a variety of stimulus delivery algorithms to be incorporated dependent on the patient's requirements. The developed system consists of a stimulator unit, stimulator firmware, external sensors, a programmer unit, two stimulation channels and electrodes. A clinician specifies a suitable algorithm for a particular patient and then selects the relevant stimulus parameters for that algorithm using the programmer unit. The stimulator unit's architecture supports the addition of future algorithms. The device was developed in accordance with the European Medical Devices Directive 93/42/EEC resulting in the need for a well-defined development lifecycle during the design and development of the neuromuscular stimulator. This development lifecycle must place emphasis on the need to identify potential hazards. Therefore, the adoption of a use case/task driven approach as one of the strategies in eliciting the requirements, both functional and non-functional and specification stages of the development lifecycle resulted in a more rigid hazard/risk analysis leading ultimately to a more robust final system. A comprehensive review of the literature has revealed that use cases have been in use in other contexts but not so in a biomedical context. Therefore, this is a novel strategy to the development of a device in this field. A brief background on the historical development of drop foot stimulators shall be presented thereby displaying the benefits of the programmability feature of our stimulator.

Patient acceptability and experiences of therapeutic switching of proton pump inhibitors within the National Preferred Drugs initiative in Ireland.

INTRODUCTION: A 'Preferred Drugs' initiative was introduced into Ireland in 2013. This identified a single recommended drug to be prescribed to patients requiring treatment from a particular class of drugs. AIMS: This study investigates how patients on established proton pump inhibitor (PPI) therapy experienced the therapeutic switching of their medication to the 'preferred drug', and the extent to which they regarded it as an acceptable practice. METHODS: The experiences of 61 patients on established proton pump inhibitor (PPI) therapy were sought before and after their drug was switched to the 'preferred drug'. RESULTS: Eighty per cent of patients were happy to switch medications. When asked for their opinions on medications in general, 71% felt doctors should prescribe the least expensive medication, 84% agreed that all licensed medications were safe while 67% felt their GP changing medication for cost reasons was safe. After 8 weeks, 20% of patients had switched back to their old PPI. When asked how they felt about their medication change, 74% felt happy or pleased. CONCLUSIONS: The majority of patients in our study were satisfied to have their medication switched. However, prescribers should be mindful that 1 in 5 patients encountered problems as a result of the switching process.

A system for the delivery of programmable, adaptive stimulation intensity envelopes for drop foot correction applications.

We describe the design of an intelligent drop foot stimulator unit for use in conjunction with a commercial neuromuscular electrical nerve stimulation (NMES) unit, the NT2000. The developed micro-controller unit interfaces to a personal computer (PC) and a graphical user interface (GUI) allows the clinician to graphically specify the shape of the stimulation intensity envelope required for a subject undergoing drop foot correction. The developed unit is based on the ADuC812S micro-controller evaluation board from Analog Devices and uses two force sensitive resistor (FSR) based foot-switches to control application of stimulus. The unit has the ability to display to the clinician how the stimulus intensity envelope is being delivered during walking using a data capture capability. The developed system has a built-in algorithm to dynamically adjust the delivery of stimulus to reflect changes both within the gait cycle and from cycle to cycle. Thus, adaptive control of stimulus intensity is achieved.

An electrode configuration technique using an electrode matrix arrangement for FES-based upper arm rehabilitation systems.

An upper limb electrical stimulation technique has been developed which features a novel self-configuration approach, to obtain an ideal wrist response from the patient. The system uses an analogue de-multiplexer in conjunction with an electrode matrix so that different electrode sites can be tested using only one channel of stimulation. A twin axis goniometer is attached to the patient's wrist and flex sensors are attached to the patient's fingers so that the control algorithm can assess the wrist response. A data acquisition unit logs the data for further analysis. A clinical investigation on healthy subjects was conducted to test the proposed system. The results show a high variation in hand response across different subjects. In addition, for all subjects tested an ideal response was found which shows some justification for the use of the proposed technique.