OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019.
EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs).
FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles.
CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.
EXPERIMENTAL APPROACH: Natural products were screened against human or mouse P2X4 activity using fura-2 loaded 1321N1 cells for measurement of intracellular Ca2+ responses. Whole-cell currents were measured by patch clamp. Human primary macrophage chemokine release was used to assess effect of taspine on inflammatory cell function. An enzymatic assay was performed to assess the effect of taspine on recombinant PI3-kinase.
KEY RESULTS: A natural product screen identified taspine as an inhibitor of human P2X4 activity. Taspine inhibits human and mouse P2X4-mediated Ca2+ influx in 1321N1 cells expressing receptors but lacked activity at human P2X2, P2X3, P2X2/3 and P2X7 receptors. Taspine inhibited the maximal response at human and mouse P2X4 but effective on ATP potency. Taspine has a slow onset rate (~15 min for half-maximal inhibition), irreversible over 30 min of washout. Taspine inhibits P2X4-mediated Ca2+ signalling in mouse BV-2 microglia cells and human primary macrophage. Taspine inhibited P2X4-mediated CXCL5 secretion in human primary macrophage. Taspine reversed ivermectin-induced potentiation of P2X4 currents in 1321N1 stably expressing cells. The PI3-kinase inhibitor LY294002 mimicked the properties of taspine on P2X4-mediated Ca2+ influx and whole-cell currents. Taspine directly inhibited the enzymatic activity of recombinant PI3-kinase in a competitive manner.
CONCLUSION AND IMPLICATIONS: Taspine is a novel natural product P2X4 receptor inhibitor, mediating its effect through PI3-kinase inhibition rather than receptor antagonism. Taspine can inhibit the pro-inflammatory signalling by P2X4 in human primary macrophage.
RESULTS: Out of the six clinical trials selected, a significant impact of trauma was observed in individuals in all but one paper. Gender predilection varied across studies and could not be conclusively determined. The follow-up period ranged from two months to two years in the trials. The odds ratio (OR) 0.38 [0.19, 0.77] and the risk ratio (RR) 0.52 [0.32, 0.85] indicated that both the odds as well as the relative risk of experiencing dental trauma were lower in the group with negligible impact compared to the group with noticeable impact. Conclusion and further implications: The findings show that dental trauma significantly affects orthodontic parameters, with lower risk and likelihood of suffering dental trauma in the group with negligible impact than in the group with noticeable impact. However, given the substantial heterogeneity among the studies, it is advised to exercise caution when extrapolating the findings to all populations. Registration and protocol: Registration in the PROSPERO database was carried out before initiating the investigation [CRD42023407218].
METHODS: In this prospective study, 48 patients scheduled for elective laparotomy were randomized to two groups of preemptive analgesia, namely, group K-P, in which anestheologists administered a combination of 0.3 mg/kg IV ketamine and 40.0 mg IV parecoxib, or group K, in which ones gave 0.3 mg/kg IV ketamine alone. Patients from both groups underwent surgery under general anesthesia, and total intraoperative opioid requirement was recorded. After surgery, morphine administered by automated patient-controlled analgesia (PCA) infusion device was initiated in all patients. Pain score was assessed using the visual analogue scale (VAS), and postoperative opioid requirement was recorded at 1 and 4 hours, and subsequently from 4-hour intervals up to 24 hours after surgery.
RESULTS: Compared to group K, group K-P required significantly lower rescue IV fentanyl in the recovery bay (0.10 ± 0.28 vs. 0.35 ± 0.46 μg/kg; P = 0.031), showing prolonged time-to-first analgesic request recorded by PCA device (70.8 ± 40.0 vs. 22.2 ± 15.8 mins; P ＜ 0.001), lower total morphine requirement delivered by PCA device (8.0 ± 4.6 vs. 16.8 ± 6.5 mg; P ＜ 0.001), and lower VAS values measured at all time points. There was no significant difference in intraoperative total opioid requirement between the groups.
CONCLUSIONS: Among laparotomy patients, multimodal preemptive analgesia by the use of a combination of low-dose IV ketamine and IV parecoxib was more effective than IV ketamine alone in reducing pain scores and postoperative analgesia requirement (e.g., PCA-administered morphine).
METHODS: The International Society of Global Health (ISoGH) used the Child Health and Nutrition Research Initiative (CHNRI) method to identify research priorities for future pandemic preparedness. Eighty experts in global health, translational and clinical research identified 163 research ideas, of which 42 experts then scored based on five pre-defined criteria. We calculated intermediate criterion-specific scores and overall research priority scores from the mean of individual scores for each research idea. We used a bootstrap (n = 1000) to compute the 95% confidence intervals.
RESULTS: Key priorities included strengthening health systems, rapid vaccine and treatment production, improving international cooperation, and enhancing surveillance efficiency. Other priorities included learning from the coronavirus disease 2019 (COVID-19) pandemic, managing supply chains, identifying planning gaps, and promoting equitable interventions. We compared this CHNRI-based outcome with the 14 research priorities generated and ranked by ChatGPT, encountering both striking similarities and clear differences.
CONCLUSIONS: Priority setting processes based on human crowdsourcing - such as the CHNRI method - and the output provided by ChatGPT are both valuable, as they complement and strengthen each other. The priorities identified by ChatGPT were more grounded in theory, while those identified by CHNRI were guided by recent practical experiences. Addressing these priorities, along with improvements in health planning, equitable community-based interventions, and the capacity of primary health care, is vital for better pandemic preparedness and response in many settings.