Fatal poisoning in drug addicts in the Nordic countries in 2017

This study is the seventh report on fatal poisonings among drug addicts in the Nordic countries. In this report, we analyse data from the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. Data on gender, number of deaths, places of deaths, age, main intoxicants and substances detected in blood were recorded to obtain national and comparable Nordic data, and to allow comparison with earlier studies conducted in 1984, 1991, 1997, 2002, 2007 and 2012. The death rate (number of deaths per 100,000 inhabitants) was highest in Iceland (6.58) followed closely by Sweden (6.46) and then lowest in Denmark (4.29). The death rate increased in Finland (5.84), Iceland and Sweden and decreased in Denmark compared to earlier studies. The death rate in Norway, which has decreased since 2002, has stabilised around 5.7 as of 2017. Women accounted for 7-23% of the fatal poisonings. The percentage was lowest in Iceland and highest in Finland and Norway. The age range was 14-70 years. The median age (41 years) was highest in Denmark and Norway. The other countries had a median age between 33 and 35 years. Opioids were the main cause of death. Methadone remained the main intoxicant in Denmark, while heroin/morphine was still the main intoxicant in Norway, as was buprenorphine in Finland. However, the picture has changed in Sweden compared to 2012, where heroin/morphine caused most deaths in 2017. Sweden also experienced the highest number of deaths from fentanyl analogues (67 deaths) and buprenorphine (61 deaths). Deaths from fentanyl analogues also occurred in Denmark, Finland and Norway, but to a smaller extent. Over the years, the proportion of opioid deaths has decreased in all countries except Sweden, which has experienced an increase. This decline has been replaced by deaths from CNS stimulants like cocaine, amphetamine and methylenedioxymethamphetamine (MDMA). Cocaine deaths have occurred in all countries but most frequently in Denmark. MDMA deaths have increased in all countries but mostly in Finland. Poly-drug use was widespread, as seen in the earlier studies. The median number of detected drugs per case varied from 4-6. Heroin/morphine, methadone, buprenorphine, cocaine, amphetamine, methamphetamine, MDMA, tetrahydrocannabinol (THC) and benzodiazepines were frequently detected. Pregabalin and gabapentin were detected in all countries, especially pregabalin, which was detected in 42% of the Finnish cases. New psychoactive substances (NPS) occurred in all countries except Iceland. (C) 2020 Elsevier B.V. All rights reserved.Peer reviewe

Imaging in population science: cardiovascular magnetic resonance in 100,000 participants of UK Biobank - rationale, challenges and approaches

PMCID: PMC3668194SEP was directly funded by the National Institute for Health Research Cardiovascular Biomedical Research Unit at Barts. SN acknowledges support from the Oxford NIHR Biomedical Research Centre and from the Oxford British Heart Foundation Centre of Research Excellence. SP and PL are funded by a BHF Senior Clinical Research fellowship. RC is supported by a BHF Research Chair and acknowledges the support of the Oxford BHF Centre for Research Excellence and the MRC and Wellcome Trust. PMM gratefully acknowledges training fellowships supporting his laboratory from the Wellcome Trust, GlaxoSmithKline and the Medical Research Council

Linkage disequilibrium pattern of the ATM gene in breast cancer patients and controls; association of SNPs and haplotypes to radio-sensitivity and post-lumpectomy local recurrence

<p>Abstract</p> <p>Background</p> <p>The ATM protein is activated as a result of ionizing radiation, and genetic variants of the <it>ATM </it>gene may therefore affect the level of radiation-induced damage. Individuals heterozygous for <it>ATM </it>mutations have been reported to have an increased risk of malignancy, especially breast cancer.</p> <p>Materials and methods</p> <p>Norwegian breast cancer patients (272) treated with radiation (252 of which were evaluated for radiation-induced adverse side effects), 95 Norwegian women with no known history of cancer and 95 American breast cancer patients treated with radiation (44 of which developed ipsilateral breast tumour recurrence, IBTR) were screened for sequence variations in all exons of the <it>ATM </it>gene as well as known intronic variants by denaturating high performance liquid chromatography (dHPLC) followed by sequencing to determine the nature of the variant.</p> <p>Results and Conclusion</p> <p>A total of 56 variants were identified in the three materials combined. A borderline significant association with breast cancer risk was found for the 1229 T>C (Val>Ala) substitution in exon 11 (P-value 0.055) between the Norwegian controls and breast cancer patients as well as a borderline significant difference in haplotype distribution (P-value 0.06). Adverse side effects, such as: development of costal fractures and telangiectasias, subcutaneous and lung fibrosis, pleural thickening and atrophy were evaluated in the Norwegian patients. Significant associations were found for several of the identified variants such as rs1800058 (Leu > Phe) where a decrease in minor allele frequency was found with increasing level of adverse side effects for the clinical end-points pleural thickening and lung fibrosis, thus giving a protective effect. Overall our results indicate a role for variation in the <it>ATM </it>gene both for risk of developing breast cancer, and in radiation induced adverse side effects. No association could be found between risk of developing ipsilateral breast tumour recurrence and any of the sequence variants found in the American patient material.</p

The apoptosis-inducing activity towards leukemia and lymphoma cells in a cyanobacterial culture collection is not associated with mouse bioassay toxicity

Cyanobacteria (83 strains and seven natural populations) were screened for content of apoptosis (cell death)-inducing activity towards neoplastic cells of the immune (jurkat acute T-cell lymphoma) and hematopoetic (acute myelogenic leukemia) lineage. Apoptogenic activity was frequent, even in strains cultured for decades, and was unrelated to whether the cyanobacteria had been collected from polar, temperate, or tropic environments. The activity was more abundant in the genera Anabaena and Microcystis compared to Nostoc, Phormidium, Planktothrix, and Pseudanabaena. Whereas the T-cell lymphoma apoptogens were frequent in organic extracts, the cell death-inducing activity towards leukemia cells resided mainly in aqueous extracts. The cyanobacteria were from a culture collection established for public health purposes to detect toxic cyanobacterial blooms, and 54 of them were tested for toxicity by the mouse bioassay. We found no correlation between the apoptogenic activity in the cyanobacterial isolates with their content of microcystin, nor with their ability to elicit a positive standard mouse bioassay. Several strains produced more than one apoptogen, differing in biophysical or biological activity. In fact, two strains contained microcystin in addition to one apoptogen specific for the AML cells, and one apoptogen specific for the T-cell lymphoma. This study shows the potential of cyanobacterial culture collections as libraries for bioactive compounds, since strains kept in cultures for decades produced apoptogens unrelated to the mouse bioassay detectable bloom-associated toxins

The Physical Activity and Fitness in Childhood Cancer Survivors (PACCS) Study: Protocol for an International Mixed Methods Study

BackgroundSurvivors of childhood cancer represent a growing population with a long life expectancy but high risks of treatment-induced morbidity and premature mortality. Regular physical activity (PA) may improve their long-term health; however, high-quality empirical knowledge is sparse.ObjectiveThe Physical Activity and Fitness in Childhood Cancer Survivors (PACCS) study comprises 4 work packages (WPs) aiming for the objective determination of PA and self-reported health behavior, fatigue, and quality of life (WP 1); physical fitness determination (WP 2); the evaluation of barriers to and facilitators of PA (WP 1 and 3); and the feasibility testing of an intervention to increase PA and physical fitness (WP 4).MethodsThe PACCS study will use a mixed methods design, combining patient-reported outcome measures and objective clinical and physiological assessments with qualitative data gathering methods. A total of 500 survivors of childhood cancer aged 9 to 18 years with >= 1 year after treatment completion will be recruited in follow-up care clinics in Norway, Denmark, Finland, Germany, and Switzerland. All participants will participate in WP 1, of which approximately 150, 40, and 30 will be recruited to WP 2, WP3, and WP 4, respectively. The reference material for WP 1 is available from existing studies, whereas WP 2 will recruit healthy controls. PA levels will be measured using ActiGraph accelerometers and self-reports. Validated questionnaires will be used to assess health behaviors, fatigue, and quality of life. Physical fitness will be measured by a cardiopulmonary exercise test, isometric muscle strength tests, and muscle power and endurance tests. Limiting factors will be identified via neurological, pulmonary, and cardiac evaluations and the assessment of body composition and muscle size. Semistructured, qualitative interviews, analyzed using systematic text condensation, will identify the perceived barriers to and facilitators of PA for survivors of childhood cancer. In WP 4, we will evaluate the feasibility of a 6-month personalized PA intervention with the involvement of local structures.ResultsEthical approvals have been secured at all participating sites (Norwegian Regional Committee for Medical Research Ethics [2016/953 and 2018/739]; the Oslo University Hospital Data Protection Officer; equivalent institutions in Finland, Denmark [file H-19032270], Germany, and Switzerland [Ethics Committee of Northwestern and Central Switzerland, project ID: 2019-00410]). Data collection for WP 1 to 3 is complete. This will be completed by July 2022 for WP 4. Several publications are already in preparation, and 2 have been published.ConclusionsThe PACCS study will generate high-quality knowledge that will contribute to the development of an evidence-based PA intervention for young survivors of childhood cancer to improve their long-term care and health. We will identify physiological, psychological, and social barriers to PA that can be targeted in interventions with immediate benefits for young survivors of childhood cancer in need of rehabilitation.</p

ESC guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 2-care pathways, treatment, and follow-up

Aims: Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular (CV) disease in association with COVID-19. Methods and results: A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, which was reported previously, focused on the epidemiology, pathophysiology, and diagnosis of CV conditions that may be manifest in patients with COVID-19. This second part addresses the topics of: care pathways and triage systems and management and treatment pathways, both of the most commonly encountered CV conditions and of COVID-19; and information that may be considered useful to help patients with CV disease (CVD) to avoid exposure to COVID-19. Conclusion: This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities

European Society of Cardiology guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 1-epidemiology, pathophysiology, and diagnosis

Aims:Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two-part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular disease (CVD) in association with COVID-19. Methods and results: A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, reported here, focuses on the epidemiology, pathophysiology, and diagnosis of cardiovascular (CV) conditions that may be manifest in patients with COVID-19. The second part, which will follow in a later edition of the journal, addresses the topics of care pathways, treatment, and follow-up of CV conditions in patients with COVID-19. Conclusion: This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities