Mcleodbugge6160
Even with relatively high vaccination coverage, Japan experienced rubella epidemics in 2012-2014 and 2018-2019, which were fueled by untraced imported cases. We aimed to develop a risk map for rubella epidemics in Japan by geographic location via analysis of seroepidemiological data and accounting for the abundance of foreign visitors.
Geographic age distribution and seroprevalence were used to compute the age- and sex-dependent next-generation matrix in each region. We computed the probability of a major epidemic using the assumed number of untraced imported rubella cases proportionally modeled to the number of foreign travelers.
Risks of a major epidemic were high in areas with capital cities, while areas with a greater fraction of older people yielded smaller effective reproduction numbers, a lower volume of foreign travelers, and thus a lower probability of a major epidemic. The volume of susceptible adult males was larger in urban geographic regions, having a greater number of foreign travelers than remote areas.
Our findings are consistent with the observation of multiple large clusters of rubella cases in urban areas during 2012-2014 and 2018-2019. Should a future rubella epidemic occur, it will likely be in geographic areas with capital cities.
Our findings are consistent with the observation of multiple large clusters of rubella cases in urban areas during 2012-2014 and 2018-2019. Should a future rubella epidemic occur, it will likely be in geographic areas with capital cities.To date, SARS-CoV-2 (the virus that causes COVID-19) has spread to almost every region of the world, infecting millions and resulting in the deaths of hundreds of thousands of people. Although it was predicted that Africa would suffer a massive loss of life due to this pandemic, the number of COVID-19 cases has been relatively low across the continent. Researchers have speculated that several factors may be responsible for this outcome in Africa, including the extensive experience that countries have with infectious diseases and the young median age of their populations. However, it is still important for African countries to adopt aggressive and bold approaches against COVID-19, in case the nature of the pandemic changes. This short review will summarize the status of the outbreak in Africa and propose possible reasons for current trends, as well as discuss interventions aimed at preventing a rapid increase in the number of COVID-19 cases in the future.
Immune checkpoint inhibitors (ICIs) and thoracic radiotherapy are increasingly used to treat advanced cancers. Despite data indicating exaggerated radiation toxicities in patients with autoimmune disease, the safety of thoracic radiotherapy in patients with prior ICI-associated immune-related adverse events (irAEs) is undefined.
Patients treated from 2014 to 2020 with ICIs were queried for receipt of corticosteroids and radiotherapy. Patients who received thoracic radiation after symptomatic irAEs were assessed for ≥grade 2 radiation pneumonitis (RP). Characteristics predictive of RP were assessed using logistic regression and response relationships were modeled.
Among 496 assessed patients, 41 with irAE history subsequently treated with thoracic radiotherapy were analyzed. Most irAEs were grade 2 (n= 21) and 3 (n= 19). Median time from irAE onset to radiotherapy was 8.1 months. Most patients received stereotactic body radiation therapy (n= 20) or hypofractionated radiotherapy (n= 18). In total, 25 patiThis is the first study assessing the toxicity of radiotherapy among patients with prior irAEs from ICIs. Patients with prior irAEs were found to be at very high risk for clinically significant and persistent RP from thoracic radiotherapy. Careful consideration should be given to the possibility of an increased risk of RP, and close monitoring is recommended in these patients.
Treatment with tivozanib, a highly selective and potent vascular endothelial growth factor receptor tyrosine kinase inhibitor, has demonstrated single-agent efficacy in advanced renal cell carcinoma (RCC) along with minimal off-target toxicities and a favorable adverse event (AE) profile. We report final results from TiNivo, a phase Ib/II study of tivozanib combined with nivolumab.
In phase Ib, patients with metastatic RCC received tivozanib 1.0 mg once daily (QD) for 21 days followed by 7 days off treatment (n= 3) or tivozanib 1.5 mg QD (n= 3) plus nivolumab 240 mg every 2 weeks. The maximum tolerated dose was determined to be tivozanib 1.5 mg, and 22 additional patients were enrolled at the maximum tolerated dose for phase II. Primary end points included safety and tolerability, with secondary end points of objective response rate, disease control rate, and progression-free survival.
In total, 25 patients were treated with tivozanib 1.5 mg QD [12 (48%) treatment-naïve; 13 (52%) previously treated]. Treatment-related grade 3/4 AEs were reported in 20 patients (80%); 4 patients (17%) experienced AEs that led to dose reduction, and 8 (32%) discontinued due to AEs. The objective response rate was 56% (including one complete response) and disease control rate was 96%, with a median time to best response of 7.9 weeks. Twenty patients (80%) had tumor shrinkage. With a median follow-up of 19.0 months (range, 12.6-22.8), median progression-free survival was 18.9 months (95% confidence interval 16.4-not reached) in all patients and was similar in treatment-naïve and previously treated patients.
Tivozanib plus nivolumab combination therapy showed a generally tolerable AE profile and promising antitumor efficacy. UPF 1069 These results support further development of tivozanib combined with nivolumab as a treatment option in patients with treatment-naïve or previously treated metastatic RCC.
NCT03136627.
NCT03136627.Emphysema is a chronic respiratory disease characterized by interalveolar septa destruction and enlarged air sacs. How the inhalation dosimetry in the pulmonary acini varies in the time course of emphysema is still unclear. The aim of this study is to numerically evaluate the impact of septal destructions on particle deposition in a pyramid-shape subacinar model that is composed of 496 alveoli. Four emphysematous models were generated by progressively removing the inter-alveolar septa from the normal geometry. Spatial distribution and temporal evolution of particle deposition were quantified in expanding/contracting subacinar models on both total and regional basis using a well-validated discrete-phase Lagrangian model. Airflow fields in the subacinar cavities are sensitive to the septal raptures, with regular, radial streamlines in the proximal alveoli in the normal geometry in contrast to unsymmetrical and recirculating flows in the emphysematous subacini. Intensified collateral ventilation and significantly increased doses in the outer wall and base are observed in disease than heath.
