Background To understand the impact of the COVID-19 pandemic on mortality, this study investigates overall, sex- and age-specific excess all-cause mortality in 20 countries, during 2020. Methods Total, sex- and age-specific weekly all-cause mortality for 2015–2020 was collected from national vital statistics databases. Excess mortality for 2020 was calculated by comparing weekly 2020 observed mortality against expected mortality, estimated from historical data (2015–2019) accounting for seasonality, long- and short-term trends. Crude and age-standardized rates were analysed for total and sex-specific mortality. Results Austria, Brazil, Cyprus, England and Wales, France, Georgia, Israel, Italy, Northern Ireland, Peru, Scotland, Slovenia, Sweden, and the USA displayed substantial excess age-standardized mortality of varying duration during 2020, while Australia, Denmark, Estonia, Mauritius, Norway, and Ukraine did not. In sex-specific analyses, excess mortality was higher in males than females, except for Slovenia (higher in females) and Cyprus (similar in both sexes). Lastly, for most countries substantial excess mortality was only detectable (Austria, Cyprus, Israel, and Slovenia) or was higher (Brazil, England and Wales, France, Georgia, Italy, Northern Ireland, Sweden, Peru and the USA) in the oldest age group investigated. Peru demonstrated substantial excess mortality even in the <45 age group. Conclusions This study highlights that excess all-cause mortality during 2020 is context dependent, with specific countries, sex- and age-groups being most affected. As the pandemic continues, tracking excess mortality is important to accurately estimate the true toll of COVID-19, while at the same time investigating the effects of changing contexts, different variants, testing, quarantine, and vaccination strategies.
BackgroundPhysicians working in critical and intensive care settings encounter death of chronic incurable patients on a daily basis; however they have scant skills on how to communicate with the patients and their family members. The aim of the present survey is to examine communication of critical and intensive care physicians with patients’ family members receiving treatment due to chronic incurable diseases/conditions and to compare the views of families with physicians working in critical and intensive care settings.MethodsThe survey was conducted in four cities of Georgia (Tbilisi, Kutaisi, Batumi and Telavi) in 2014. Physicians working in critical and intensive care settings and family members were asked to fill in separate questionnaires, covering various aspects of communication including patients’ prognosis, ways of death occurrence, treatment plans and religion. Participants ranked their responses on a scale ranging from “0” to “10”, where “0” represented “never” and “10”-“always”. After data collection, responses were recoded into three categories: 0–3 = never/rarely, 4–7 = somewhat and 8–10 = often/always. Differences were tested using Pearson’s chi-square or Fisher’s exact test as appropriate. P value of < 0.05 was considered as significant.ResultsSixty-five physicians and 59 patients’ family members participated in this cross-sectional study. Majority of their responses was statistically significantly different. Only one quarter (23.7 %) of family members of patients receiving medical aid in critical and intensive care settings were satisfied with the communication level. In contrast, 78.5 % of physicians considered their communication with families as positive (p < 0.0001).ConclusionsThe survey revealed the mismatch between the views on communication of critical and intensive care settings physicians and family members of the patients with chronic incurable diseases receiving care in critical and intensive care settings. In order to provide the best care for chronic incurable patients and their family members, physicians working in critical and intensive care settings must have relevant clinical knowledge and ability to provide effective communication. Present results reflect important potential targets for educational interventions including critical and intensive care physicians training through online modules.Electronic supplementary materialThe online version of this article (doi:10.1186/s12904-016-0135-2) contains supplementary material, which is available to authorized users.
The number of paediatric patients living with a prolonged Disorder of Consciousness (DoC) is growing in high-income countries, thanks to substantial improvement in intensive care. Life expectancy is extending due to the clinical and nursing management achievements of chronic phase needs, including infections. However, long-known pharmacological therapies such as amantadine and zolpidem, as well as novel instrumental approaches using direct current stimulation and, more recently, stem cell transplantation, are applied in the absence of large paediatric clinical trials and rigorous age-balanced and dose-escalated validations. With evidence building up mainly through case reports and observational studies, there is a need for well-designed paediatric clinical trials and specific research on 0–4-year-old children. At such an early age, assessing residual and recovered abilities is most challenging due to the early developmental stage, incompletely learnt motor and cognitive skills, and unreliable communication; treatment options are also less explored in early age. In middle-income countries, the lack of rehabilitation services and professionals focusing on paediatric age hampers the overall good assistance provision. Young and fast-evolving health insurance systems prevent universal access to chronic care in some countries. In low-income countries, rescue networks are often inadequate, and there is a lack of specialised and intensive care, difficulty in providing specific pharmaceuticals, and lower compliance to intensive care hygiene standards. Despite this, paediatric cases with DoC are reported, albeit in fewer numbers than in countries with better-resourced healthcare systems. For patients with a poor prospect of recovery, withdrawal of care is inhomogeneous across countries and still heavily conditioned by treatment costs as well as ethical and cultural factors, rather than reliant on protocols for assessment and standardised treatments. In summary, there is a strong call for multicentric, international, and global health initiatives on DoC to devote resources to the paediatric age, as there is now scope for funders to invest in themes specific to DoC affecting the early years of the life course.
5533 Background: NOX66 is a new formulation of the small molecule, idronoxil. The primary mechanism of action of idronoxil stems from its binding to the transmembrane enzyme ENOX2 expressed on cancer cells, resulting in reduced S1P and increased ceramide levels, thereby promoting apoptosis. Additional intracellular effects include the inhibition of DNA repair mechanisms. There is growing evidence that S1P is a promotor of tumour resistance to immune cell infiltration, highlighting NOX66’s potential to modulate the immune response against cancer. Methods: This two-part phase 1b open-label study enrolled patients with late-stage progressive mCRPC. Part 1 was a dose-escalation safety assessment of three doses of NOX66 (400 mg, n = 4; 800 mg, n = 6 and 1200 mg, n = 15) administered daily for 14 days with radiation therapy (20 Gy) delivered in 5 fractionated doses to one or more symptomatic lesion/s. Part 2 was an expansion cohort with NOX66 at 1200 mg in conjunction with radiation therapy. The primary endpoint of safety was assessed by the frequency and grade of treatment-emergent adverse events (TEAEs). At 6 weeks, 3- and 6-month follow up, treatment response was assessed radiographically by RECIST1.1 and by PSA >50% reduction. Results: 25 patients received and completed treatment. TEAEs considered related to NOX66 alone were mild (Grade 1) cases of dry mouth and oral mucositis; mild (Grade 1) fatigue was considered related to both NOX66 and radiation. None of the 21 Grade ≥3 TEAEs were considered related to NOX66. At 6 months, of the 15 evaluable patients by RECIST1.1, 9 had SD and 1 had PR and these same patients had maintained this response from 3 months. Five of the 16 PSA-evaluable patients achieved a PSA response (61-98% PSA reduction) at 6 months, which again was maintained from 3 months. Conclusions: NOX66 in combination with low-dose radiation therapy was found to be safe and well tolerated with promising signals of durable efficacy in patients with late-stage mCRPC. Responses of lesions outside the radiation field are being reviewed. Clinical trial information: NCT03307629 .
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