Presentation and management of diabetic ketoacidosis in adults in Malta

Aim: The aim of this audit was to assess adherence to local guideline in the management of Diabetic Ketoacidosis (DKA). Method: Patients admitted with DKA between April 2013 and March 2015 were identified and data was retrospectively collected from patients’ confidential files and Isoft®. Data collected included initial parameters recorded and biochemical investigations taken (initial and subsequent assessment of pH, HCO3-, blood glucose, potassium levels and urinary ketones), insulin regime started and intravenous fluid administered. Results: During the established time period 40 cases of DKA were identified in 18 patients. Median age was 33 years with a female preponderance of 60%. Six patients had newly diagnosed diabetes mellitus while 8 patients had more than one admission of DKA. All cases had capillary blood glucose monitoring (BGM) and/or venous random blood (plasma) glucose (RBG) checked and pH and HCO3- recorded on admission. 0.9% sodium chloride was the intravenous fluid started in all cases (as recommended by the guideline) and a median of 6.75L was prescribed during the first 24 hours. The median time spent on intravenous insulin infusion was 42.7 hours while the median time to pH >7.30, HCO3- >15mmol/L and negligible urinary ketones were 6.88, 12.83 and 34.5 hours respectively. Subcutaneous insulin was started at a median time of 48.21 hours from initiation of DKA protocol. Conclusion: This audit showed good adherence to local guideline. The great discrepancy between the time to pH >7.3 and the time to negligible urinary ketones highlights the need to introduce tools to measure systemic ketone production in the management of DKA with an update in the current local clinical practice guideline.peer-reviewe

Identification of an HNF1A p.Gly292fs frameshift mutation presenting as diabetes during pregnancy in a Maltese family

The diagnosis of maturity onset diabetes of the young (MODY) is a challenging process in view of the extensive clinical and genetic heterogeneity of the disease. Mutations in the gene encoding hepatocyte nuclear factor 1α (HNF1A) are responsible for most forms of monogenic diabetes in Northern European populations. Genetic analysis through a combination of whole exome sequencing and Sanger sequencing in three Maltese siblings and their father identified a rare duplication/frameshift mutation in exon 4 of HNF1A that lies within a known mutational hotspot in this gene. In this report, we provide the first description of an HNF1A-MODY3 phenotype in a Maltese family. The findings reported are relevant and new to a regional population, where the epidemiology of atypical diabetes has never been studied before. This report is of clinical interest as it highlights how monogenic diabetes can be misdiagnosed as either type 1, type 2, or gestational diabetes. It also reinforces the need for a better characterisation of monogenic diabetes in Mediterranean countries, particularly in island populations such as Malta with a high prevalence of diabetes.peer-reviewe

Antibiotic-resistant genes and bacteria as evolving contaminants of emerging concerns (e-CEC): is it time to include evolution in risk assessment?

The pressing issue of the abundance of antibiotic resistance genes and resistant bacteria in the environment (ARGs and ARB, respectively) requires procedures for assessing the risk to health. The chemo-centric environmental risk assessment models identify hazard(s) in a dose–response manner, obtaining exposure, toxicity, risk, impact and policy. However, this risk assessment approach based on ARGs/ARB evaluation from a quantitative viewpoint shows high unpredictability because ARGs/ARB cannot be considered as standard hazardous molecules: ARB duplicate and ARGs evolve within a biological host. ARGs/ARB are currently listed as Contaminants of Emerging Concern (CEC). In light of such characteristics, we propose to define ARGs/ARB within a new category of evolving CEC (or e-CEC). ARGs/ARB, like any other evolving determinants (e.g., viruses, bacteria, genes), escape environmental controls. When they do so, just one molecule left remaining at a control point can form the origin of a new dangerous and selection-responsive population. As a consequence, perhaps it is time to acknowledge this trait and to include evolutionary concepts within modern risk assessment of e-CEC. In this perspective we analyze the evolutionary responses most likely to influence risk assessment, and we speculate on the means by which current methods could measure evolution. Further work is required to implement and exploit such experimental procedures in future risk assessment protocols

The bacterial urban resistome: recent advances

Cities that are densely populated are reservoirs of antibiotic resistant genes (ARGs). The overall presence of all resistance genes in a specific environment is defined as a resistome. Spatial proximity of surfaces and different hygienic conditions leads to the transfer of antibiotic resistant bacteria (ARB) within urban environments. Built environments, public transportation, green spaces, and citizens’ behaviors all support persistence and transfer of antimicrobial resistances (AMR). Various unique aspects of urban settings that promote spread and resilience of ARGs/ARB are discussed: (i) the role of hospitals and recreational parks as reservoirs; (ii) private and public transportation as carriers of ARGs/ARB; (iii) the role of built environments as a hub for horizontal gene transfer even though they support lower microbial biodiversity than outdoor environments; (iv) the need to employ ecological and evolutionary concepts, such as modeling the fate of a specific ARG/ARB, to gain enhanced health risk assessments. Our understanding and our ability to control the rise of AMR in an urban setting is linked to our knowledge of the network connecting urban reservoirs and the environment

LDV Measurement of Confined Parallel Jet Mixing

Laser Doppler Velocimetry (LDV) measurements were taken in a confinement, bounded by two parallel walls, into which issues a row of parallel jets. Two-component measurements were taken of two mean velocity components and three Reynolds stress components. As observed in isolated three dimensional wall bounded jets, the transverse diffusion of the jets is quite large. The data indicate that this rapid mixing process is due to strong secondary flows, transport of large inlet intensities and Reynolds stress anisotropy effects

LDV Measurement of Confined Parallel Jet Mixing

Laser Doppler Velocimetry (LDV) measurements were taken in a confinement, bounded by two parallel walls, into which issues a row of parallel jets. Two-component measurements were taken of two mean velocity components and three Reynolds stress components. As observed in isolated three dimensional wall bounded jets, the transverse diffusion of the jets is quite large. The data indicate that this rapid mixing process is due to strong secondary flows, transport of large inlet intensities and Reynolds stress anisotropy effects

Case Report Hepatitis E Infection in a Renal Transplant Recipient

An asymptomatic 35-year-old renal transplant recipient was noted to have deranged liver function tests. Liver biopsy revealed a portal inflammatory process with mild lobular activity and portal fibrous expansion, consistent with a virally mediated process. An extensive viral screen confirmed infection with Hepatitis E virus genotype 3 (HEV-3). There is increased awareness about locally acquired Hepatitis E virus (HEV) infection in the transplant population in the UK. The important implications of this infection are becoming more apparent as progression to liver cirrhosis can occur. However, the incidence, natural history, and treatment of HEV infection in the transplant population are not well established. This report illustrates a case of delayed spontaneous clearance of the HEV infection

Thyroid nodules, FNA cytology and thyroid cancer in Malta

INTRODUCTION: Thyroid nodules are very common and elucidating the nature of these thyroid nodules is an important task.METHODOLOGY: Patients who had an ultrasound guided fine needle aspiration (FNA) of a thyroid nodule between January 2008 and June 2012 were retrospectively audited and their ultrasonographic and biochemical characteristics where analysed. For those patients who were operated nodule characteristics were correlated with thyroid histology.RESULTS: 397 thyroid aspirates were identified. Using The Betsheda System for Reporting Thyroid Cytopathology (TBSRTC) 59.5% were classified as category II (benign), 15.4% category IV (follicular) 4.8% category V (suspicious for malignancy) and 8.4% category VI (malignant). Statistical analysis of operated patients (n=97) yielded a positive predictive value for malignancy (for those who were classified according to TBSRTC categories V and VI) of 89.5%, a negative predictive value of 86.4%, sensitivity of 81.0% and specificity of 92.7%. 42 patients who were operated had thyroid malignancy, of whom 41 had a papillary carcinoma and 1 patient had a medullary thyroid carcinoma. The mean age at presentation was 48.0 years (S.D.±12.6 years), the mean largest diameter of the papillary carcinomas was 13.8 mm (S.D.±8.6 mm) and 48.8% had lymph node involvement. 58.5% of patients with malignant histology had more than 1 focus of malignancy in the thyroid. The mean size of thyroid nodule on ultrasound of these patients was 17.5 mm (S.D.±9.4 mm), 53.7% had a hypoechoic nodule and 48.8% had microcalcifications. These findings differed from those who had a follicular adenoma on histology, where 13.0% had a hypoechoic nodule on ultrasound and 16.1% had microcalcifications.CONCLUSIONS: These findings further establish that FNA of thyroid nodules is a very important and helpful tool in the management of thyroid nodules. Important characteristics of thyroid cancer are shown including the high rate of multifocality seen in our patient cohort.peer-reviewe

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment