Ebola : too far or so close?

The year 2014 has witnessed the escalation of the largest ever Ebola outbreak which started in Guinea, and later spread to other countries in West Africa. The associated disease burden has already exceeded the total number of cases in all the sporadic outbreaks that occurred since the first description of Ebola in 1976. The threat of further spread across Africa, and possibly beyond through international travel, is of concern and has led several countries around the world to implement preparedness measures against Ebola. In an attempt to contain the spread of Ebola, WHO and other non- governmental humanitarian organisations have pooled their resources to fuel efforts at improving patient care, isolation facilities, healthcare worker training, and availability of personal protective equipment in the affected countries. The outbreak has brought to light the lack of past investment in research into treatment or potential vaccine development against the Ebola virus, with the only hope of expediting a cure that can be used in the current outbreak being through the launch of clinical trials investigating experimental drugs in the affected countries.peer-reviewe

Excision margins in breast conserving surgery

The ideal excision margin in breast conserving surgery is still a matter of debate. The aim is to see if there is any correlation between increasing excision margin distance and local recurrence rate. Patients who had breast conserving surgery at Mater Dei Hospital in 2009 had their notes reviewed retrospectively. Patient demograpichs, including the excision margins were recorded. Local recurrences within a 3 year follow up period were noted. Chi square was used to compare categorical data and a p value of less than 0.05 was considered statistically significant. 91 patients were recruited into the study. 74 patients (81.5%) had negative margins (>1mm), 10 patients (11%) had close margins (<1mm) while 7 patients (7.5%) had positive margins. 5 patients (5.5%) had local recurrence. The highest recurrence rate (14%) was in patients with positive margins, and no statistical signficant difference in recurrence rates was noted with wider excision margins. As long as the margins are negative, increasing excision margins will not result in a better local recurrence rate.peer-reviewe

Climate change and human illness : a hot topic?

Global climate change, now proven to occur under the influence of human activity, can affect human health and illness. Aside from the risk of natural disasters and diminishing fresh-water supply and arable land, climate change maintains a complex relationship with both communicable and non-communicable forms of illness. The epidemiology of infectious diseases, whether viral, parasitic, or bacterial, has shown to change under the influence of climate, particularly in the case of vector-borne zoonoses. Non-communicable disease, however, including allergic, respiratory, cardiovascular and dermatological, are also influenced by global and regional changes in climate.While further research in this area is recommended, the role of the clinician in educating communities on the negative health impact of climate change, as well as the potential benefit of sustainable healthcare policy, are yet to be defined.peer-reviewe

Assessing the home management of hypoglycaemia in paediatric T1DM

Objectives: The home management of hypoglycaemia is an essential part of diabetes care. All carers of children with T1DM in Malta receive education on managing hypoglycaemia at the time of initial diagnosis. While this education is often revisited at subsequent appointments, it is not always retained and put into practice. We conducted a survey to assess Maltese carers’ knowledge of how to manage suspected episodes of hypoglycaemia in their children, as well as identify areas where carers feel least confident. Methods: All Maltese patients under the age of 16 years with T1DM were included. A questionnaire was formulated to assess various aspects of hypoglycaemia management that any carer of a child with T1DM might be expected to know. The carer of each patient with T1DM was contacted a minimum of 6 months following the diagnosis of T1DM. Results: 117 carers of children with T1DM were interviewed by telephone or in person. While most correctly described appropriate first-line management of suspected hypoglycaemia, only 21% recognized the need to place an unconscious child in the lateral recumbent position, and only 53% suggested they would avoid giving anything by mouth in such an event. Over 80% felt confident in managing hypoglycaemia, but 78% feared using intramuscular glucagon. Conclusions: This survey highlights areas of knowledge that parents of children with T1DM lack despite regular education. Doctors taking care of children with T1DM should regularly assess carers’ knowledge, and discuss specific areas of concern.peer-reviewe

Gentamicin therapeutic drug monitoring in neonates : an observational study

BACKGROUND: Gentamicin is important in the treatment of suspected neonatal sepsis, while also potentially oto- and nephrotoxic. Therapeutic drug monitoring of serum gentamicin levels (SGL) helps to prevent this. We present an investigation into the influence of birthweight, gestational age, and appropriateness-for-gestational age on the rates of high SGLs amongst neonates treated for suspected sepsis.METHODS: Case notes of neonates admitted to the neonatal and paediatric intensive care unit from 2013-2017 who received intravenous gentamicin treatment were reviewed. The dosing regimen, SGL, and demographic details were recorded. Trough SGLs ≥2mg/L before the 2nd gentamicin dose were taken as indicative of unsafe levels. Mean SGLs and percentage of safe SGLs were compared for each category (birthweight, gestational age, appropriateness-of-weight-for-gestational age) using odds ratios (Student’s t-test), ‘N-1’ Chi squared test, and correlation coefficient.RESULTS: In total 170 neonatal gentamicin results were analysed. Nineteen (11.2%) of these were ³2mg/L. Stratifying the results according to birthweight showed significantly higher mean gentamicin levels in neonates weighing 3kg (0.71mg/L; 95% CI 0.57-0.85). Premature neonates born at 28 weeks’ gestation or less had significantly higher mean gentamicin levels (1.69mg/L; 95% CI: 1.33-2.04) than those born at term (0.84mg/L; 95% CI: 0.68-0.99mg/L).CONCLUSIONS: While the current gentamicin dosing guidelines are safe, extremely premature neonates born under 28 weeks are at higher risk for high gentamicin trough levels and potential toxicity. Extended interval gentamicin dosing may have a role in mitigating for this.peer-reviewe

Foundation doctors' audits : effective or not?

Editor, The UK Foundation Programme (FP) curriculum recommends that Foundation doctors (FD) develop experience in ‘managing, analysing and presenting at least one quality improvement project and using the results to improve patient care’ While the Maltese FP follows the UKFP recommendations, little emphasis is placed on completion of the audit cycle. The authors devised a questionnaire to assess the proportion of audits performed by FDs at Mater Dei Hospital (MDH) that completed the audit cycle, implementing changes in clinical practice.peer-reviewe

Georisks in the Mediterranean and their mitigation

An international scientific conference organised by the Seismic Monitoring and Research Unit, Department of Geoscience, Faculty of Science, Department of Civil and Structural Engineering and Department of Construction and Property Management, Faculty of the Built Environment, University of Malta.Part of the SIMIT project: Integrated civil protection system for the Italo-Maltese cross-border area. Italia-Malta Programme – Cohesion Policy 2007-2013This conference is one of the activities organised within the SIMIT strategic project (Integrated Cross-Border Italo-Maltese System of Civil Protection), Italia-Malta Operational Programme 2007 – 2013. SIMIT aims to establish a system of collaboration in Civil Protection procedures and data management between Sicilian and Maltese partners, so as to guarantee the safety and protection of the citizens and infrastructure of the cross-border area. It is led by the Department of Civil Protection of the Sicilian region, and has as other partners the Department of Civil Protection of Malta and the Universities of Palermo, Catania and Malta. SIMIT was launched in March 2013, and will come to a close in October 2015. Ever since the initial formulation of the project, it has been recognised that a state of national preparedness and correct strategies in the face of natural hazards cannot be truly effective without a sound scientific knowledge of the hazards and related risks. The University of Malta, together with colleagues from other Universities in the project, has been contributing mostly to the gathering and application of scientific knowledge, both in earthquake hazard as well as in building vulnerability. The issue of seismic hazard in the cross-border region has been identified as deserving foremost importance. South-East Sicily in particular has suffered on more than one occasion the effects of large devastating earthquakes. Malta, although fortunately more removed from the sources of such large earthquakes, has not been completely spared of their damaging effects. The drastic increase in the building density over recent decades has raised the level of awareness and concern of citizens and authorities about our vulnerability. These considerations have spurred scientists from the cross-border region to work together towards a deeper understanding of the underlying causes and nature of seismic and associated hazards, such as landslide and tsunami. The SIMIT project has provided us with the means of improving earthquake surveillance and analysis in the Sicily Channel and further afield in the Mediterranean, as well as with facilities to study the behaviour of our rocks and buildings during earthquake shaking. The role of the civil engineering community in this endeavour cannot be overstated, and this is reflected in the incorporation, from the beginning, of the civil engineering component in the SIMIT project. Constructing safer buildings is now accepted to be the major option towards human loss mitigation during strong earthquakes, and this project has provided us with a welcome opportunity for interaction between the two disciplines. Finally the role of the Civil Protection authorities must occupy a central position, as we recognize the importance of their prevention, coordination and intervention efforts, aided by the input of the scientific community. This conference brings together a diversity of geoscientists and engineers whose collaboration is the only way forward to tackling issues and strategies for risk mitigation. Moreover we welcome the contribution of participants from farther afield than the Central Mediterranean, so that their varied experience may enhance our efforts. We are proud to host the conference in the historic city of Valletta, in the heart of the Mediterranean, which also serves as a constant reminder of the responsibility of all regions to protect and conserve our collective heritage.peer-reviewe

Genomic analysis of the Meningococcal ST-4821 complex – western clade, potential sexual transmission and predicted antibiotic susceptibility and vaccine coverage

Introduction: The ST-4821 complex (cc4821) is a leading cause of serogroup C and serogroup B invasive meningococcal disease in China where diverse strains in two phylogenetic groups (groups 1 and 2) have acquired fluoroquinolone resistance. cc4821 was recently prevalent among carriage isolates in men who have sex with men in New York City (USA). Genome-level population studies have thus far been limited to Chinese isolates. The aim of the present study was to build upon these with an extended panel of international cc4821 isolates. Methods: Genomes of isolates from Asia (1972 to 2017), Europe (2011 to 2018), North America (2007), and South America (2014) were sequenced or obtained from the PubMLST Neisseria database. Core genome comparisons were performed in PubMLST. Results: Four lineages were identified. Western isolates formed a distinct, mainly serogroup B sublineage with alleles associated with fluoroquinolone susceptibility (MIC &lt;0.03 mg/L) and reduced penicillin susceptibility (MIC 0.094 to 1 mg/L). A third of these were from anogenital sites in men who have sex with men and had unique denitrification gene alleles. Generally 4CMenB vaccine strain coverage was reliant on strain-specific NHBA peptides. Discussion: The previously identified cc4821 group 2 was resolved into three separate lineages. Clustering of western isolates was surprising given the overall diversity of cc4821. Possible association of this cluster with the anogenital niche is worthy of monitoring given concerns surrounding antibiotic resistance and potential subcapsular vaccine escape

The seventh national communication of Malta under the United Nations framework convention on climate change

This is the fourth time that Malta is submitting a National Communication under the United Nations Framework Convention on Climate Change (UNFCCC), following the submission of a First National Communication in 2004 and a Second National Communication in 2010. This is also the second time that Malta is submitting such a Communication since its accession to Annex I status under the Convention, the first two submissions having been made as a non-Annex I Party. Emission reduction or limitation commitments applicable to Malta Malta’s status under the Convention up to the time it applied for accession to Annex I, and with that accession being conditional to not taking on quantified emission limitation or reduction targets for the first commitment period of the Kyoto Protocol, meant that until 2012 Malta was not subject to an economy-wide greenhouse gas related obligation under the Protocol. This however did not mean that Malta had no obligations to limit or reduce emissions from anthropogenic activities taking place in the country. In line with, Malta will be contributing its fair share of the EU’s unconditional commitment under the Convention to reduce emissions by 20% below 1990 levels by 2020. This is in line with the target inscribed in the amendments to the Kyoto Protocol (the Doha Amendments), that will be jointly fulfilling the second commitment period with the other Union member states; therefore, emissions from the aforementioned power plants remain subject to compliance with EU Emissions Trading Scheme provisions, while the Effort-Sharing Decision target is the principal emissions mitigation obligation that the country has until 2020, for all other greenhouse gas emissions. The major point sources of greenhouse gas emissions in Malta, namely the electricity generation plants have been, since of 2005, subject to the EU Emissions Trading Scheme, whereby they are required to surrender allowances in respect of emissions of carbon dioxide. Emissions of greenhouse gases not covered by the EU Emissions Trading Scheme, are subject to an overall limit under the so-called Effort-Sharing Decision. Under this decision, Malta must limit such greenhouse gases to not more than 5% over emission levels in 2005, by 2020. The EU is already looking towards the longer-term future, with the 2030 climate and energy framework providing for a 40% domestic reduction target for 2030. Legislative implementation of this goal is currently under discussion at EU level.peer-reviewe

Neuroinflammation, autoinflammation, splenomegaly and anemia caused by bi-allelic mutations in IRAK4

We describe a novel, severe autoinflammatory syndrome characterized by neuroinflammation, systemic autoinflammation, splenomegaly, and anemia (NASA) caused by bi-allelic mutations in IRAK4. IRAK-4 is a serine/threonine kinase with a pivotal role in innate immune signaling from toll-like receptors and production of pro-inflammatory cytokines. In humans, bi-allelic mutations in IRAK4 result in IRAK-4 deficiency and increased susceptibility to pyogenic bacterial infections, but autoinflammation has never been described. We describe 5 affected patients from 2 unrelated families with compound heterozygous mutations in IRAK4 (c.C877T (p.Q293*)/c.G958T (p.D320Y); and c.A86C (p.Q29P)/c.161 + 1G&gt;A) resulting in severe systemic autoinflammation, massive splenomegaly and severe transfusion dependent anemia and, in 3/5 cases, severe neuroinflammation and seizures. IRAK-4 protein expression was reduced in peripheral blood mononuclear cells (PBMC) in affected patients. Immunological analysis demonstrated elevated serum tumor necrosis factor (TNF), interleukin (IL) 1 beta (IL-1β), IL-6, IL-8, interferon α2a (IFN-α2a), and interferon β (IFN-β); and elevated cerebrospinal fluid (CSF) IL-6 without elevation of CSF IFN-α despite perturbed interferon gene signature. Mutations were located within the death domain (DD; p.Q29P and splice site mutation c.161 + 1G&gt;A) and kinase domain (p.Q293*/p.D320Y) of IRAK-4. Structure-based modeling of the DD mutation p.Q29P showed alteration in the alignment of a loop within the DD with loss of contact distance and hydrogen bond interactions with IRAK-1/2 within the myddosome complex. The kinase domain mutation p.D320Y was predicted to stabilize interactions within the kinase active site. While precise mechanisms of autoinflammation in NASA remain uncertain, we speculate that loss of negative regulation of IRAK-4 and IRAK-1; dysregulation of myddosome assembly and disassembly; or kinase active site instability may drive dysregulated IL-6 and TNF production. Blockade of IL-6 resulted in immediate and complete amelioration of systemic autoinflammation and anemia in all 5 patients treated; however, neuroinflammation has, so far proven recalcitrant to IL-6 blockade and the janus kinase (JAK) inhibitor baricitinib, likely due to lack of central nervous system penetration of both drugs. We therefore highlight that bi-allelic mutation in IRAK4 may be associated with a severe and complex autoinflammatory and neuroinflammatory phenotype that we have called NASA (neuroinflammation, autoinflammation, splenomegaly and anemia), in addition to immunodeficiency in humans