Two decades of action on nutrition for the Maltese population

Malta, like many other countries, has experienced significant challenges in nutrition over the past 20 years. Given the increasing prevalence of diet-related diseases and overweight and obesity across all ages, nutrition has been high on the Ministry for Health agenda over the past 15 years. Public Health practitioners in Malta have been drivers of public health nutrition reform throughout this period. The Health Promotion and Disease Prevention Directorate was set up to mainly focus on health promotion and non-communicable diseases including healthy nutrition in 2007. Over the years a number of strategies have been outlined targeting nutrition for the Maltese population including the Non Communicable Disease Strategy, the National Cancer Plan, the National Healthy Weight for Life Strategy, the Food and Nutrition Policy and Action Plan for Malta, Diabetes: A National Public Health Priority – A National Strategy for Diabetes 2016-2020, Whole of School Approach to Healthy Lifestyle: Healthy Eating and Physical Activity Policy and Strategy and the National Breastfeeding Policy and Action Plan 2015 – 2020. With input from WHO and the EU, Malta has participated in many surveys allowing for continuous monitoring and evaluation. In 2015, Malta embarked on a first National Food Consumption Survey, results of which will provide a baseline on eating habits to target priority areas for action, inform policy and monitor trends.peer-reviewe

Giant gastric folds in a patient with hypoalbuminaemia

A 70-year-old man presented with a 3-month history of persistent epigastric pain, 8 kg weight loss and lower limb swelling. Examination revealed a normal abdomen and bilateral lower limb oedema. Blood results were unremarkable except for hypoalbuminaemia (23 g/l) and peripheral eosinophilia (1.06×109/l). Urinalysis and CT of the abdomen were negative. An oesophagogastroduodenoscopy (OGD) revealed large gastric folds involving the fundus and the body of the stomach (figure 1), and a small antral polyp. Histology showed marked reactive mucosal changes, pronounced foveolar hyperplasia and cystic dilatation (figure 2), compatible with a diagnosis of Ménétrier’s disease. Helicobacter pylori was absent and the antral polyp was adenomatous. He was given omeprazole and prednisolone (20 mg daily), which was tailed down after 2 months. Subsequently, his symptoms improved significantly. He regained 10 kg in weight and his albumin levels normalised. OGD done post therapy and 1 year later still showed prominent, but less pronounced, gastric folds, and histological evidence of hyperplastic gastropathy.peer-reviewe

Maternal preconception intake of folic acid in Malta

Background: Neural tube defects (NTDs) are serious birth defects arising from abnormalities in neural tube development during early embryogenesis. Research shows that taking folic acid (FA) prior to and throughout the first 12 weeks of pregnancy will significantly decrease the occurrence of NTDs. The prevalence of NTDs in Malta is 10.0/10,000 births, yet this rate can be brought down to 5.0-6.0/10,000 births with preconception FA. This study aims to investigate the maternal intake of preconception FA in Malta. Methods: The National Obstetric Information System (NOIS) collects detailed demographic, pregnancy, delivery and infant outcome data on all births in Malta. One of the variables recorded at the first antenatal visit is whether the mother took FA prior to pregnancy. NOIS data for 2015 was obtained, Excel and SPSS were used for analysis. Results: 4385 women delivered a baby in 2015, of these 1125 (25.7%) reported taking FA before pregnancy. Both univariate and multivariate logistic regression showed that maternal age, parity, education, nationality, locality of residence, marital status, planned pregnancy and use of artificial reproductive technology were all significantly associated with taking preconception FA (p<0.001). Conclusion: Although preconception folic acid supplementation has been advised since the early 1990s, in Malta only a quarter of mothers are taking this before pregnancy. This low compliance is also documented in other countries. Several maternal factors have been found to be associated with better intake of preconception FA. Effective methods of increasing maternal preconception intake of FA are necessary to decrease the rate of NTDs in Malta.peer-reviewe

Tenofovir as rescue therapy following clinical failure to lamivudine in severe acute hepatitis B

Acute hepatitis B (AHB) is a self-limiting condition in more than 95% of cases. Treatment is however recommended in patients with severe AHB (<1% of cases), aiming to prevent liver failure and death. Various nucleos(t)ide analogues (NA) have been found to be effective in severe AHB, although NA-resistant strains causing AHB have been also recently reported. The use of tenofovir in severe AHB has only been described in 3 cases (1 adult and 1 infant with HBV mono-infection, 1 adult with HBV/HIV co-infection). We hereby report a 47-year-old treatment-naïve male, who developed severe AHB and was initially treated with lamivudine (LMV). Initial rapid biochemical response was followed by biochemical breakthrough after 9 days, suggesting LMV resistance. Rescue therapy with ‘add-on’ tenofovir brought about a sustained improvement in biochemical, serological and virological markers until HBsAg was lost after 4 months. Thus, this is the second adult HBV mono-infected patient, who responded successfully to tenofovir in severe AHB.peer-reviewe

The lived experience of having a parent in a residential home : the daughter’s perspective

Introduction: Immediate family members are a critical source of support and informal care in late life, such family members play an important role in the admission and transition of the older person into residential homes (RH). Research has shown that, after spouses, daughters of older people are usually those who take up most of the responsibilities of care within the care-receiver's family. This study therefore aimed at exploring the lived experience of daughters whose parents were currently living in a RH. Methods: A qualitative method using interpretative phenomenological approach was adopted. Data was collected via audio recorded individual semi-structured interviews with six participants who were recruited through purposive sampling from the state residential home.peer-reviewe

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma.

ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action

Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways

UNLABELLED: Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma. SIGNIFICANCE: Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA. See related commentary by Shain, p. 1294. This article is highlighted in the In This Issue feature, p. 1275

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

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies