ACE inhibitors, angiotensin receptor blockers and endothelial injury in COVID-19.

BACKGROUND: COVID-19 is caused by the coronavirus SARS-CoV-2, which uses angiotensin-converting enzyme 2 (ACE-2) as a receptor for cellular entry. It is theorized that ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) may increase vulnerability to SARS-CoV-2 by upregulating ACE-2 expression, but ACE-I/ARB discontinuation is associated with clinical deterioration. OBJECTIVE: To determine whether ACE-I and ARB use is associated with acute kidney injury (AKI), macrovascular thrombosis and in-hospital mortality. METHODS: A retrospective, single-centre study of 558 hospital inpatients with confirmed COVID-19 admitted from 1 March to 30 April 2020, followed up until 24 May 2020. AKI and macrovascular thrombosis were primary end-points, and in-hospital mortality was a secondary end-point. RESULTS: AKI occurred in 126 (23.1%) patients, 34 (6.1%) developed macrovascular thrombi, and 200 (35.9%) died. Overlap propensity score-weighted analysis showed no significant effect of ACE-I/ARB use on the risk of occurrence of the specified end-points. On exploratory analysis, severe chronic kidney disease (CKD) increases odds of macrovascular thrombi (OR: 8.237, 95% CI: 1.689-40.181, P = 0.009). The risk of AKI increased with advancing age (OR: 1.028, 95% CI: 1.011-1.044, P = 0.001) and diabetes (OR: 1.675, 95% CI: 1.065-2.633, P = 0.025). Immunosuppression was associated with lower risk of AKI (OR: 0.160, 95% CI: 0.029-0.886, P = 0.036). Advancing age, dependence on care, male gender and eGFR < 60 mL min-1 /1.73 m2 increased odds of in-hospital mortality. CONCLUSION: We did not identify an association between ACE-I/ARB use and AKI, macrovascular thrombi or mortality. This supports the recommendations of the European and American Societies of Cardiology that ACE-Is and ARBs should not be discontinued during the COVID-19 pandemic.

The effectiveness of Reslizumab in severe asthma treatment: a real-world experience.

BACKGROUND: Increased numbers of blood and sputum eosinophils are associated with higher exacerbation frequency and increased asthma severity. In clinical trials, targeting Interleukin-5 has been shown to be a useful therapeutic strategy for patients with severe eosinophilic asthma. METHODS: Twenty-six patients have been commenced on Reslizumab in our institution since early 2017. Safety and clinical efficacy parameters were recorded at regular intervals. RESULTS: Mean ACQ-6 score at the start of treatment was 3.5. The average number of exacerbations in the year preceding treatment was 8.3 per person. 30% of patients had been admitted to hospital at least once over the 12 months preceding therapy. 54% of our patients were on long term oral steroid. Our data showed sustained improvement of Asthma control (Mean improvement in ACQ-6 was 1.7 at 1 year, and 2.0 at 2 years, P = 0.0001). Of the patients who were on long term systemic steroids, 35.7% discontinued steroids completely, with a mean reduction of prednisolone dose of 5.2 mg at 1 year. There was a 79% reduction in the annual exacerbation frequency at 1 year, and 88% at 2 years (P = < 0.0001). Modest, albeit statistically significant increases in creatine kinase which seemed to plateau by 1 year were noted. CONCLUSIONS: Overall, Reslizumab was well tolerated with discontinuation of treatment due to side effects recorded in only one patient. Our data confirm the utility of anti-IL5 therapy in a carefully selected phenotype of severe asthma with evidence of eosinophilic airway inflammation.

Randomised controlled trial of an intervention to improve parental knowledge and management practices of fever.

BACKGROUND: We know that parents require resources which can assist them to improve fever knowledge and management practices. The purpose of this study, using an RCT, was to examine the effectiveness of an information leaflet at increasing parental knowledge of fever, specifically temperature definition. METHODS: A prospective, multi-centre, randomised, two-parallel arm, controlled trial with blinded outcome ascertainment was conducted. Parents presenting at purposively selected healthcare facilities who had a child aged ≤5 years of age were invited to participate. An information leaflet for use in the trial was designed based on previous studies with parents. Parents in the intervention arm read an information leaflet on fever and management of fever in children, completed a short questionnaire at Time 1 (T1) and again 2 weeks after randomisation at Time 2 (T2). Parents in the control arm did not receive the fever information leaflet but completed the same questionnaire as the intervention arm at T1 and againat T2. The primary outcome was the correct definition of fever (higher than ≥38 °C). RESULTS: A total of 100 parents participated in the study at T1. A greater proportion of the intervention group (76%) than the control group (28%) selected the correct temperature (≥38 °C) at T1. 76% of the intervention arm correctly identified "higher than ≥38°C" as the temperature at which a fever is said to be present compared to 28% of the control arm. After 2 weeks, there was an increase of 6% of parents in the intervention arm (increase to 82.4%) who gave the correct temperature compared to just a 2.8% increase in the control arm (increase to 30.8%). Univariate logistic regression showed that parents in the intervention arm were significantly more likely to give the correct answer at both time-points (T1: OR 8.1; CI 95% 3.3-19.9: p < 0.01; T2: OR 10.5; CI 95% 3.4-32.0: p < 0.01). CONCLUSIONS: Our RCT of this simple educational intervention has been shown to improve parental understanding of fever knowledge and correct management strategies. Education interventions providing simple, clear information is a key step to decreasing parental mismanagement of fever and febrile illness in children. TRIAL REGISTRATION: ClinicalTrials.gov NCT02903342, September 16, 2016, Retrospectively registered.

The Prevalence of Severe Sepsis or Septic Shock in an Irish Emergency Department.

Severe sepsis and septic shock are among the leading causes of death globally. Despite the central role the emergency department (ED) plays in the early identification of patients presenting to hospital with sepsis, the prevalence of severe sepsis and septic shock in the Irish ED setting has not been described. The primary aim of this study was to measure the prevalence of severe sepsis or septic shock in an Irish adult ED setting. The clinical records of patients presenting to the ED over a four-week period were retrospectively reviewed to determine if they met the current Health Service Executive (HSE) criteria for severe sepsis or septic shock. Overall, 3,585 adult patients attended the ED during the study period, with 42 patients meeting the criteria for severe sepsis or septic shock. The ED prevalence of severe sepsis or septic shock was 11.7 patients (95% CI 8.1 - 15.4%) per 1000 ED attendances.

Risk factors for nonpurulent leg cellulitis: a systematic review and meta-analysis.

Nonpurulent cellulitis is an acute bacterial infection of the dermal and subdermal tissues that is not associated with purulent drainage, discharge or abscess. The objectives of this systematic review and meta-analysis were to identify and appraise all controlled observational studies that have examined risk factors for the development of nonpurulent cellulitis of the leg (NPLC). A systematic literature search of electronic databases and grey literature sources was performed in July 2015. The Newcastle-Ottawa Scale (NOS) was used to assess methodological quality of included studies. Of 3059 potentially eligible studies retrieved and screened, six case-control studies were included. An increased risk of developing NPLC was associated with previous cellulitis [odds ratio (OR) 40·3, 95% confidence interval (CI) 22·6-72·0], wound (OR 19·1, 95% CI 9·1-40·0), current leg ulcers (OR 13·7, 95% CI 7·9-23·6), lymphoedema/chronic leg oedema (OR 6·8, 95% CI 3·5-13·3), excoriating skin diseases (OR 4·4, 95% CI 2·7-7·1), tinea pedis (OR 3·2, 95% CI 1·9-5·3) and body mass index > 30 kg m-2 (OR 2·4, 95% CI 1·4-4·0). Diabetes, smoking and alcohol consumption were not associated with NPLC. Although diabetics may have been underrepresented in the included studies, local risk factors appear to play a more significant role in the development of NPLC than do systemic risk factors. Clinicians should consider the treatment of modifiable risk factors including leg oedema, wounds, ulcers, areas of skin breakdown and toe-web intertrigo while administering antibiotic treatment for NPLC.

Which intravenous bronchodilators are being administered to children presenting with acute severe wheeze in the UK and Ireland?

During a prospective 10-week assessment period, 3238 children aged 1-16 years presented with acute wheeze to Paediatric Emergency Research in the UK and Ireland centres. 110 (3.3%) received intravenous bronchodilators. Intravenous magnesium sulfate (MgSO4) was used in 67 (60.9%), salbutamol in 61 (55.5%) and aminophylline in 52 (47.3%) of cases. In 35 cases (31.8%), two drugs were used together, and in 18 cases (16.4%), all three drugs were administered. When used sequentially the most common order was salbutamol, then MgSO4, then aminophylline. Overall, 30 different intravenous treatment regimens were used varying in drugs, dose, rate and duration.

Idiopathic Toe Walking: A Gait Laboratory Review.

Idiopathic toe walking (ITW) is defined as one who is neurologically normal but demonstrates a preference for walking on the toes. It is a diagnosis of exclusion so differential diagnoses such as cerebral palsy, neuropathy or myopathy must be ruled out. A review of 102 patients attending a gait laboratory with a presumptive diagnosis of ITW found that gait analysis data agreed with this diagnosis in 81 (79.4%) of cases while the remaining 21 (20.6%) were not typical of this diagnosis. The features found to be significantly different between the groups were Babinski response, fast stretch of the gastrocnemius, knee flexion at initial contact and asymmetry at the ankles during gait. This study highlights that clinical gait analysis can be a useful, non-invasive means of diagnosing idiopathic toe walking and recommending appropriate intervention based on clinical and dynamic assessment of calf tightness.

Intraoperative asystole associated with fibroid uterus.

The authors present the case of a patient with a large retroperitoneal fibroid whose laparotomy was abandoned due to intraoperative asystole. Perioperative management and possible etiological factors are discussed in this paper.

A pilot cross-sectional study of patients presenting with cellulitis to emergency departments.

To characterise the Emergency Department (ED) prevalence of cellulitis, factors predicting oral antibiotic therapy and the utility of the Clinical Resource Efficiency Support Team (CREST) guideline in predicting patient management in the ED setting, a prospective, cross-sectional study of consecutive adult patients presenting to 3 Irish EDs was performed. The overall prevalence of cellulitis was 12 per 1,000 ED visits. Of 59 patients enrolled, 45.8% were discharged. Predictors of treatment with oral antibiotics were: CREST, Class 1 allocation (odds ratio (OR) 6.81, 95% Cl =1.5-30.1, p=0.012), patient self-referral (OR= 6.2, 95% Cl 1.9- 20.0, p=0.03) and symptom duration longer than 48 hours (OR 1.2, 95% Cl = 1.0-1.5,p=0.049). In conflict with guideline recommendation, 43% of patients in CREST Class 1 received IV therapy. Treatment with oral antibiotics was predicted by CREST Class 1 allocation, self-referral, symptom duration of more than 48 hours and absence of pre-EO antibiotic therapy.

Impact of video vector analysis of ankle foot orthoses in children with physical disability: A 10-year clinical review.

BACKGROUND: Ankle Foot Orthoses (AFOs) are frequently prescribed to manage gait impairments in children with physical disability, and it is important that AFOs are prescribed and fitted appropriately to maximize potential benefits. AFO tuning, manipulation of the AFO footwear combination (AFO-FC) by means of video vector analysis, is routinely used to optimize AFO use. However, the incidence or types of changes that are implemented after this type of orthotic review are unknown. RESEARCH QUESTION: To investigate the impact of a multi-disciplinary video vector clinic on AFO provision in children with physical disability. METHODS: All children who attended a video vector clinic over a period of 10-years from the establishment of the clinic were included in the study. Outcomes of the clinic were grouped into 5 categories: (1) No change to AFO-FC; (2) Altered/tuned AFO-FC; (3) Discontinued AFO-FC; (4) Recast AFO; (5) Change in prescription. Data were summarised narratively. RESULTS: 141 independently ambulant children were included. The diagnoses were bilateral cerebral palsy (39 %, n=55), unilateral cerebral palsy (38 %, n=54), spina bifida (9 %, n=13), hereditary spastic paraparesis (2 %, n=3) and other (11 %, n=16). No changes were made in 52 % of cases (n=74), tuning in 22 % of cases (n=31), the AFO was recast in 13 % of cases (n=19) and discontinued in 10 % of cases (n=14). A prescription change was recommended in 3 % of cases (n=4). SIGNIFICANCE: Our findings suggest that the video vector clinic is a time efficient and effective means of assessing gait function in children with AFOs. Without assessment at the clinic, most of the children assessed would likely have been referred for a full and more time consuming 3-dimensional gait analysis. Video vector analysis at the initial AFO fitting may improve alignment and possibly reduce non-compliance at an earlier stage.

Uterine sarcoma after tamoxifen therapy for breast cancer.

Tamoxifen has been shown to significantly reduce the risk of tumour recurrence in women with receptor positive breast cancer and has been used for chemoprevention in women with both non-invasive cancer and those with a high risk of developing breast cancer. An established and accepted risk with this treatment is the increased incidence of adenocarcinoma of the endometrium. Less well recognised is uterine sarcoma, a rare and aggressive tumour accounting for under five percent of uterine malignancies, with five year survival rates in the order of 50%.

The difficulty identifying intoeing gait in cerebral palsy.

In-toeing in children with cerebral palsy can lead to functional difficulties during gait. This may require surgical management to restore a normal foot progression angle. For this reason it is important to indentify the presence of internal rotation and to establish where the abnormal rotation is occurring. This can be done relatively easily in otherwise healthy subjects by examining foot progression angle as the subject walks towards the assessor. In cerebral palsy the often severely affected gait pattern and potential asymmetry at the pelvis means that in-toeing may be more difficult to identify. Gait laboratory data of 245 subjects with cerebral palsy were studied retrospectively. Of these 102 (41.63%) demonstrated in-toeing relative to the pelvis of one or both limbs. Eleven diplegic subjects (16.18%) in-toed bilaterally giving a total of 113 in-toeing limbs for analysis. Of those, 17 (50%) hemiplegic limbs and 20 (25.32%) diplegic limbs demonstrated a foot progression angle within normal limits due to compensations at the pelvis.

Acute cerebellitis associated with dual influenza A (H1N1) and B infection.

We describe the case of a 6-year old girl who presented to our Emergency Department (ED) with acute onset of ataxia and speech disturbance. Investigative workup included a nasopharyngeal aspirate (NPA) which was influenza A (H1N1) and B positive during the 2010/2011 influenza season. Magnetic resonance imaging (MRI) of the brain confirmed findings consistent with cerebellitis.

The medium-term effects of selective dorsal rhizotomy on gait compared to a matched cerebral palsy non-SDR group: A follow-up study.

BACKGROUND: Selective dorsal rhizotomy (SDR) has been shown to improve gait in the short-term in children with cerebral palsy (CP). Further study is needed to look at the trajectory of outcomes over the longer-term. RESEARCH QUESTION: What are the medium-term effects of SDR on gait compared to a matched CP non-SDR group? METHODS: Participants underwent SDR at mean age 6.3 years and completed baseline, 1-year and 5-year follow-up gait analyses. Non-SDR participants were matched at baseline. Differences were assessed within and between groups. Kinematic variables were analysed using Statistical non-Parametric Mapping (SnPM). Other gait and clinical data were analysed using Friedman's one-way repeated measure analysis of variance and a Mann-Whitney U-test. RESULTS: The initial SDR group consisted of 29 participants, reducing to 22 at 5-year follow-up. Of these, 15 (68 %) had orthopaedic surgeries either concurrent with or in the intervening period since the SDR, mean 3.3 procedures per participant. The initial non- SDR group had 18 participants, reducing to 17 at 5-year follow-up. Of these, 13 (76 %) had orthopaedic surgeries, mean 5.7 procedures. At 1-year follow-up the SDR group had significantly improved knee extension, ankle dorsiflexion, foot progression, Gait Deviation Index, and normalised step length compared to baseline, p < 0.05, and outcomes were maintained at 5-years. At 1-year follow-up the non-SDR group kinematic patterns were unchanged, but at 5-year follow-up this group demonstrated significantly improved knee extension, ankle dorsiflexion and foot progression. There were no significant kinematic differences between the SDR and the non-SDR group at medium-term follow-up. SIGNIFICANCE: We have documented the trajectory of gait outcomes post-SDR over 3 assessments and found that short-term gait changes endured in the medium-term. However, kinematic changes were similar to a non-SDR group undergoing routine and orthopaedic care. These outcomes are important to guide surgical decision making and to manage treatment goals and expectations.

Characteristics of a later life population in a general adult community mental health service setting.

OBJECTIVES: Globally, increasing life expectancy has escalated demands on psychiatric services caring for a later life population. It is recognised that those with enduring mental illness may have specific needs with advancing age. In this study, we describe the characteristics of a population aged over 60 years attending a general adult community psychiatric service and compare demographic and clinical features across age and diagnostic categories. The study aims to gather preliminary information which may guide future local mental health service planning. METHODS: We conducted a cross-sectional observational study using retrospective chart review of all patients aged over 60 years attending four community mental health teams in North Dublin. Cohorts of attenders were stratified by age comparing 60-64 year age group with the population aged 65 years and over. Attenders were also stratified by diagnosis and regression analysis was used to determine predictors of psychotic disorder diagnosis. RESULTS: The study included 127 patients. There was a higher prevalence of psychotic disorders among those aged 65 years and over (n = 73), while those aged 60-64 years (n = 54) were more likely to have depression and non-affective, non-psychotic disorders. Among the population aged 65 years and over 78% (n = 57) were long-term psychiatric service attenders. CONCLUSIONS: The majority of the sample aged 65 years and over were long-term service attenders with a diagnosis of severe mental illness. Further research is warranted to determine optimal service delivery for later life psychiatric service attenders.

Must we review printed lab reports without checking them? A prospective analysis of emergency department practice.

This study investigated if results of haematology and biochemistry laboratory tests, carried out at the point of care in our Emergency Department, are checked by the clinician who ordered the test, mitigating the requirement to check printed reports later. Five hundred and nineteen (519) laboratory reports were examined for significant abnormal results and documentation in clinical notes. Thirty percent (30%, n = 158) of these met the inclusion criteria for 'significantly abnormal' laboratory results. Of the 158 significantly abnormal results, 34.8% (n = 55) were not documented in the ED clinical case notes. No patient was discharged inappropriately. Our study suggests it is safe to stop routinely rechecking printed biochemistry and haematology laboratory reports in our department.

The role of cell-substrate interaction in regulating osteoclast activation: potential implications in targeting bone loss in rheumatoid arthritis.

Analysis of tissues retrieved from the bone-pannus interface from patients with rheumatoid arthritis (RA) and studies in animal models of inflammatory arthritis provide strong evidence that osteoclasts, the cells that are essential for physiological bone resorption, are responsible for articular bone destruction in RA. However, current treatments that specifically target osteoclast-mediated bone resorption in RA have not been successful in preventing bone erosions, and new therapeutic strategies are needed. It has been noted that, although osteoclast precursors are present within the bone microenvironment at sites of pathological bone resorption, cells expressing the full morphological and functional properties of mature osteoclasts are restricted to the immediate bone surface and adjacent calcified cartilage. These findings provide evidence that, in addition to requirements for specific cytokines, interaction of osteoclast precursors with these mineralised matrices results in activation of specific signal pathways and the induction of unique gene products that are essential for terminal osteoclast differentiation and activation. These studies are designed to define the gene products and signalling pathways regulated by bone and calcified cartilage, to identify new molecular targets and novel therapeutic approaches for preventing osteoclast-mediated joint destruction in RA and related forms of pathological bone loss.

Crouch gait or flexed-knee gait in cerebral palsy: Is there a difference? A systematic review.

BACKGROUND: Crouch or flexed-knee gait is one of the most common pathological gait patterns in cerebral palsy (CP). Differences exist in definitions used; the degree of knee flexion, inclusion of hip or ankle position, and timing in the gait cycle. This ambiguity may be responsible for variations in prevalence rates and difficulty comparing data across studies. RESEARCH QUESTION: What are the kinematic parameters used to define crouch or flexed-knee gait in CP gait? A secondary aim was to examine the quality of data reporting, focusing on the sample characteristics, inclusion/exclusion criteria and the choice of limb included for analysis. METHODS: Articles included in this review reported on a specified cohort of adults or children with crouch or flexed-knee gait assessed with 3-dimensional gait analysis. A customised data extraction and quality assessment table was designed specific to the research question. RESULTS: The majority (75 %) of included studies used the term crouch gait. Where the pattern was defined, 80 % of crouch papers and 94 % of flexed-knee gait papers based this solely on knee position. Kinematic parameters were clearly defined when they provided objective values of knee flexion, supported this with rationale and provided a reference point in the gait cycle. Only 22 % of crouch papers and 19 % of flexed-knee gait papers provided this information. The majority of studies (67 % crouch; 90 % flexed-knee) specified which limb(s) were included for analysis with the majority including both limbs. Objective values of knee flexion ranged from 8 o to 30 o. SIGNIFICANCE: This review highlights that crouch and flexed knee are synonymous and ambiguity exists in the kinematic definition making it difficult to make compare data amongst study cohorts. Future research should provide detailed definitions including the threshold value of knee flexion, how it was derived, the timing in the gait cycle and the limb(s) included in analysis.

Tibial rotation outcomes following hamstring lengthening as part of single event multilevel surgery in children with cerebral palsy.

BACKGROUND: Hamstring lengthening remains the most common surgical procedure in the treatment of crouch gait for children with cerebral palsy (CP). While sagittal plane knee kinematics have been shown to improve post-surgery, the effects on transverse plane kinematics have not been reported. Given the differing actions of the medial and lateral hamstring muscles there is potential for change in tibial rotation post hamstring lengthening. RESEARCH QUESTION: What is the effect of medial only versus combined medial and lateral hamstring lengthening on tibial rotation during gait in children with CP? METHODS: A retrospective analysis of children with a diagnosis of CP who underwent a hamstring lengthening procedure. These children were divided into 2 groups: G1 (n = 18) had isolated medial hamstring lengthening while G2 (n = 30) had combined medial and lateral hamstring lengthening. A matched non-surgical control group (n = 15) was also included. Kinematic data were analysed pre and post-operatively. Pre-operative to post-operative outcomes for G1 and G2, a comparison at baseline for both groups and the difference in outcomes between the groups were analysed. Baseline to follow-up outcomes for the control group were also analysed. RESULTS: External tibial rotation increased significantly within groups (G1: -10°, p < 0.01; G2: -11°, p < 0.001, control: -7.7, p < 0.01), with no significant difference in the change between the intervention groups. Foot progression angles became more external in both intervention groups (G1: -15°, p < 0.001; G2: -15°, p < 0.0001) and did not change in the control group. SIGNIFICANCE: Results demonstrated similar increases in external tibial rotation, regardless of whether an isolated medial or combined medial and lateral surgery was performed. The control group demonstrated a similar change in external tibial rotation suggesting that hamstring lengthening surgery does not contribute to increased external tibial rotation in children with CP compared to what would be expected due to natural progression.