The mortality burden in children aged 5–14 years in the WHO European Region has not been comprehensively studied. We assessed the distribution and trends of the main causes of death among children ...aged 5–9 years and 10–14 years from 1990 to 2016, for 51 countries in the WHO European Region.
We used data from vital registration systems, cancer registries, and police records from 1980 to 2016 to estimate cause-specific mortality using the Cause of Death Ensemble model.
For children aged 5–9 years, all-cause mortality rates (per 100 000 population) were estimated to be 46·3 (95% uncertainty interval UI 45·1–47·5) in 1990 and 19·5 (18·1–20·9) in 2016, reflecting a 58·0% (54·7–61·1) decline. For children aged 10–14 years, all-cause mortality rates (per 100 000 population) were 37·9 (37·3–38·6) in 1990 and 20·1 (18·8–21·3) in 2016, reflecting a 47·1% (43·8–50·4) decline. In 2016, we estimated 10 740 deaths (95% UI 9970–11 542) in children aged 5–9 years and 10 279 deaths (9652–10 897) in those aged 10–14 years in the WHO European Region. Injuries (road injuries, drowning, and other injuries) caused 4163 deaths (3820–4540; 38·7% of total deaths) in children aged 5–9 years and 4468 deaths (4162–4812; 43·5% of total) in those aged 10–14 years in 2016. Neoplasms caused 2161 deaths (1872–2406; 20·1% of total deaths) in children aged 5–9 years and 1943 deaths (1749–2101; 18·9% of total deaths) in those aged 10–14 years in 2016. Notable differences existed in cause-specific mortality rates between the European subregions, from a two-times difference for leukaemia to a 20-times difference for lower respiratory infections between the Commonwealth of Independent States (CIS) and EU15 (the 15 member states that had joined the European Union before May, 2004).
Marked progress has been made in reducing the mortality burden in children aged 5–14 years over the past 26 years in the WHO European Region. More deaths could be prevented, especially in CIS countries, through intervention and prevention efforts focusing on the leading causes of death, which are road injuries, drowning, and lower respiratory infections. The findings of our study could be used as a baseline to assess the effect of implementation of programmes and policies on child mortality burden.
WHO and Bill & Melinda Gates Foundation.
Brazil leads the world in number of firearm deaths and ranks sixth by country in rate of firearm deaths per 100,000 people. This study aims to analyze trends in and burden of mortality by firearms, ...according to age and sex, for Brazil, and the association between these deaths and indicators of possession and carrying of weapons using data from the global burden of diseases, injuries, and risk factors study (GBD) 2017. We used GBD 2017 estimates of mortality due to physical violence and self-harm from firearms for Brazil to analyze the association between deaths by firearms and explanatory variables. Deaths from firearms increased in Brazil from 25,819 in 1990 to 48,493 in 2017. Firearm mortality rates were higher among men and in the 20-24 age group; the rate was 20 times higher than for women in the same age group. Homicide rates increased during the study period, while mortality rates for suicides and accidental deaths decreased. The group of Brazilian federation units with the highest firearm collection rate (median = 7.5) showed reductions in the rate of total violent deaths by firearms. In contrast, the group with the lowest firearm collection rate (median = 2.0) showed an increase in firearm deaths from 2000 to 2017. An increase in the rate of voluntary return of firearms was associated with a reduction in mortality rates of unintentional firearm deaths (r = -0.364, p < 0.001). An increase in socio-demographic index (SDI) was associated with a reduction in all firearm death rates (r = -0.266, p = 0.008). An increase in the composite index of firearms seized or collected was associated with a reduction in rates of deaths by firearm in the subgroup of females, children, and the elderly (r = -0.269, p = 0.005). There was a change in the trend of firearms deaths after the beginning of the collection of weapons in 2004. Federation units that collected more guns have reduced rates of violent firearm deaths.
Objective
To identify the independent risk factors for 30-day perioperative seizures, as well as to evaluate the effect of perioperative seizures on overall mortality and tumor recurrence among ...patients who underwent surgical resection of brain metastases.
Methods
Patients who underwent surgical resection of brain metastases at our institution between 2011 and 2019 were included. 30-day perioperative seizures were defined as the presence of any preoperative or postoperative seizures diagnosed by a neurosurgeon or neurologist within 30 days of metastases resection. Independent risk factors for 30-day perioperative seizures were evaluated using multivariate logistic regression models. Kaplan-Meier plots and Cox regression models were constructed to evaluate the effects of 30-day perioperative seizures on overall mortality and tumor recurrence. Subgroup analyses were conducted for 30-day preoperative and 30-day postoperative seizures.
Results
A total of 158 patients were included in the analysis. The mean (SD) age was 59.3 (12.0) years, and 20 (12.7%) patients had 30-day perioperative seizures. The presence of 30-day preoperative seizures (OR=41.4; 95% CI=4.76, 924; p=0.002) was an independent risk factor for 30-day postoperative seizures. Multivariate Cox regression revealed that any 30-day perioperative seizure (HR=3.25; 95% CI=1.60, 6.62; p=0.001) was independently and significantly associated with overall mortality but not tumor recurrence (HR=1.95; 95% CI=0.78, 4.91; p=0.154).
Conclusions
Among patients with resected brain metastases, the presence of any 30-day perioperative seizure was independently associated with overall mortality. This suggests that 30-day perioperative seizures may be a prognostic marker of poor outcome. Further research evaluating this association as well as the effect of perioperative antiepileptic drugs in patients with resected brain metastases may be warranted.
Obstructive sleep apnoea (OSA) is a chronic sleep disorder characterised by recurrent cyclical episodes of upper airway collapse causing apnoea or hypopnoea. Despite being highly prevalent in ...patients with cardiovascular conditions, OSA has been a neglected component in cardiovascular practice. Fortunately, in the past few decades, increasing acknowledgement of the vulnerability of cardiac patients to OSA-related stressors and its adverse cardiovascular outcomes has made it a recognised cardiovascular risk factor in practice guidelines. Consequences of OSA include oxidative stress, endothelial dysfunction, autonomic dysfunction, and increased catecholamine release. The perturbations caused by OSA not only provide a clear mechanistic link to cardiovascular disease but also to poor outcomes after coronary revascularisation. This review article focuses on the correlation of OSA to coronary revascularisation outcomes. Our team reported that OSA is present in approximately 50% of patients undergoing coronary revascularisation. Importantly, untreated OSA was found to be an independent predictor of adverse events after both percutaneous coronary intervention and coronary artery bypass grafting. Although randomised trials did not confirm the benefits of OSA treatment in improving cardiovascular outcomes, these early trials were limited by poor treatment adherence. For now, systematic screening for OSA in patients undergoing coronary revascularisation is not indicated. Yet, with the proven benefit of OSA treatment in improving blood pressure control and quality of life, screening for and treatment of OSA is still indicated if patients have reported excessive daytime sleepiness and/or suboptimally controlled hypertension.
PIEZOs are mechanosensitive ion channels that convert force into chemoelectric signals
and have essential roles in diverse physiological settings
. In vitro studies have proposed that PIEZO channels ...transduce mechanical force through the deformation of extensive blades of transmembrane domains emanating from a central ion-conducting pore
. However, little is known about how these channels interact with their native environment and which molecular movements underlie activation. Here we directly observe the conformational dynamics of the blades of individual PIEZO1 molecules in a cell using nanoscopic fluorescence imaging. Compared with previous structural models of PIEZO1, we show that the blades are significantly expanded at rest by the bending stress exerted by the plasma membrane. The degree of expansion varies dramatically along the length of the blade, where decreased binding strength between subdomains can explain increased flexibility of the distal blade. Using chemical and mechanical modulators of PIEZO1, we show that blade expansion and channel activation are correlated. Our findings begin to uncover how PIEZO1 is activated in a native environment. More generally, as we reliably detect conformational shifts of single nanometres from populations of channels, we expect that this approach will serve as a framework for the structural analysis of membrane proteins through nanoscopic imaging.
Severe influenza infection has no effective treatment available. One of the key barriers to developing host-directed therapy is a lack of reliable prognostic factors needed to guide such therapy. ...Here, we use a network analysis approach to identify host factors associated with severe influenza and fatal outcome. In influenza patients with moderate-to-severe diseases, we uncover a complex landscape of immunological pathways, with the main changes occurring in pathways related to circulating neutrophils. Patients with severe disease display excessive neutrophil extracellular traps formation, neutrophil-inflammation and delayed apoptosis, all of which have been associated with fatal outcome in animal models. Excessive neutrophil activation correlates with worsening oxygenation impairment and predicted fatal outcome (AUROC 0.817-0.898). These findings provide new evidence that neutrophil-dominated host response is associated with poor outcomes. Measuring neutrophil-related changes may improve risk stratification and patient selection, a critical first step in developing host-directed immune therapy.
Background
In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR‐Allergic Rhinitis 2018), the ...literature has expanded substantially. The ICAR‐Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence‐based findings and recommendation from the full document.
Methods
ICAR‐Allergic Rhinitis 2023 employed established evidence‐based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work.
Results
ICAR‐Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost.
Conclusion
The ICAR‐Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.
Purpose Catheter associated urinary tract infections are one of the most common health care associated infections. The condition is frequently complicated by encrustation, which blocks the catheter ...lumen. Preclinical research is limited by the lack of relevant high throughput and cost-effective animal models. Current models are restricted to female mice, associated with major transurethral loss of catheter materials during micturition, highly invasive and complex. We present an ultrasound guided, minimally invasive model that enables catheter associated urinary tract infection and catheter encrustation studies in each mouse gender. Materials and Methods Catheter segments (4 mm) were implanted in murine bladders percutaneously in 15 males and 5 females, and transurethrally in 15 females using the Seldinger technique under ultrasound guidance. Proteus mirabilis was instilled intraluminally. Catheter encrustation was monitored by ultrasound. Bacteria were quantified in urine, and catheters and encrustation were analyzed on day 6 or 21. Results Percutaneous and transurethral catheter implantations were performed in a mean ± SE 3.6 ± 0.8 vs 2.5 ± 0.5 minutes in all mice. Ultrasound confirmed that 100% and 66% of implanted catheters, respectively, remained indwelling during the study period. Catheter encrustation developed in P. mirabilis infected urine 48 hours after instillation and an increase with time was detected by ultrasound. Fourier transform spectroscopy of the encrustation confirmed a typical struvite spectrum. Control catheters remained sterile during 21 days. Conclusions Our minimally invasive, reproducible percutaneous technique is suitable for studying catheter associated urinary tract infection in each gender. Infecting urine with P. mirabilis generates a preclinical model of catheter encrustation within 3 days. The progression of encrustation can be monitored in vivo by ultrasound, making this image based model suitable for assessing novel antibacterial and anti-encrustation therapies.
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