In a phase III trial (ClinicalTrials.gov registration ID: NCT00094653), ipilimumab significantly improved survival versus a vaccine control in pretreated patients with metastatic melanoma. Here, we ...characterize outcomes of those patients who survived ≥2 years.
Patients were randomized (3 : 1 : 1) to receive ipilimumab 3 mg/kg + gp100 vaccine, ipilimumab 3 mg/kg + placebo, or gp100 vaccine alone. Baseline demographic data, duration of survival, responses, and safety among patients with ≥2 years' survival were analyzed.
Among 676 randomized patients, 474 and 259 patients had at least 2 or 3 years of potential follow-up, respectively, and were eligible for analysis. Among these, 94 (20%) and 42 (16%) survived ≥2 and ≥3 years, respectively. Survival rates at 2 and 3 years were 25% (24 of 95) and 25% (13 of 53) with ipilimumab alone and 19% (54 of 284) and 15% (24 of 156) with ipilimumab plus gp100. Safety among patients with ≥2 years' survival was comparable with the overall study population, with the onset of new ipilimumab-related toxic effect (all grades) reported in 6 of 78 (8%) patients.
Ipilimumab results in survival of ≥2 years in one-fifth of pretreated patients with 2 years potential follow-up in a phase III trial. New onset, low-grade events starting after administration of the last dose were infrequent.
NCT00094653.
•Agent-based model simulates fleet of shared, electric, autonomous vehicles (SAEVs).•Vehicle and charging scenarios show tradeoffs between investment and operations.•Each SAEV can replace 3.7–6.8 ...privately owned vehicles.•Results suggest SAEV operational costs are most sensitive to vehicle capital costs.•SAEV cost-competitiveness to non-electric vehicles hinges on recharging automation.
There are natural synergies between shared autonomous vehicle (AV) fleets and electric vehicle (EV) technology, since fleets of AVs resolve the practical limitations of today’s non-autonomous EVs, including traveler range anxiety, access to charging infrastructure, and charging time management. Fleet-managed AVs relieve such concerns, managing range and charging activities based on real-time trip demand and established charging-station locations, as demonstrated in this paper. This work explores the management of a fleet of shared autonomous electric vehicles (SAEVs) in a regional, discrete-time, agent-based model. The simulation examines the operation of SAEVs under various vehicle range and charging infrastructure scenarios in a gridded city modeled roughly after the densities of Austin, Texas.
Results based on 2009 NHTS trip distance and time-of-day distributions indicate that fleet size is sensitive to battery recharge time and vehicle range, with each 80-mile range SAEV replacing 3.7 privately owned vehicles and each 200-mile range SAEV replacing 5.5 privately owned vehicles, under Level II (240-volt AC) charging. With Level III 480-volt DC fast-charging infrastructure in place, these ratios rise to 5.4 vehicles for the 80-mile range SAEV and 6.8 vehicles for the 200-mile range SAEV. SAEVs can serve 96–98% of trip requests with average wait times between 7 and 10minutes per trip. However, due to the need to travel while “empty” for charging and passenger pick-up, SAEV fleets are predicted to generate an additional 7.1–14.0% of travel miles. Financial analysis suggests that the combined cost of charging infrastructure, vehicle capital and maintenance, electricity, insurance, and registration for a fleet of SAEVs ranges from $0.42 to $0.49 per occupied mile traveled, which implies SAEV service can be offered at the equivalent per-mile cost of private vehicle ownership for low-mileage households, and thus be competitive with current manually-driven carsharing services and significantly cheaper than on-demand driver-operated transportation services. When Austin-specific trip patterns (with more concentrated trip origins and destinations) are introduced in a final case study, the simulation predicts a decrease in fleet “empty” vehicle-miles (down to 3–4% of all SAEV travel) and average wait times (ranging from 2 to 4minutes per trip), with each SAEV replacing 5–9 privately owned vehicles.
Background
The concomitant use of tyrosine kinase inhibitors (TKIs) and proton pump inhibitors (PPIs) is a significant concern because of potential drug‐drug interaction that reduces TKI absorption, ...thus potentially reducing the effectiveness of TKIs. The objective of this study was to evaluate the prevalence and predictors of concomitant TKI‐PPI receipt and its impact on survival and therapy discontinuation in older adults with cancer.
Methods
This retrospective study used linked Surveillance, Epidemiology, and End Results‐Medicare data for the years 2007 through 2012. In total, 12,538 patients with lung cancer, renal cell cancer, chronic myelogenous leukemia, liver cancer, or pancreatic cancer were included. The primary exposure variable was concomitant receipt of TKI‐PPI, defined as at least 30 days of PPI use in the first 90 days from the start of the TKI (exposure period). The outcomes measured were overall survival and discontinuation of therapy in 90 days and 1 year after the end of the exposure period. Cox proportional‐hazards regression with inverse probability of treatment weighting was used to evaluate the association between exposure and outcome.
Results
The overall prevalence of TKI‐PPI receipt was 22.7%. Predictors that were associated with increased use included polypharmacy and prior PPI receipt. TKI‐PPI use decreased survival in 90 days (hazard ratio, 1.16; 95% confidence interval, 1.05‐1.28) and in 1 year (hazard ratio, 1.10; 95% confidence interval, 1.04‐1.18) but was not associated with discontinuation.
Conclusions
Nearly 1 in 4 older adults with cancer who receive TKIs also receive PPIs concomitantly, and concomitant use is associated with an increased risk of death. Concerted efforts to manage medications are needed to identify and reduce the receipt of PPIs when TKIs are initiated.
Nearly 1 in 4 older adults with cancer concomitantly receive interacting tyrosine kinase inhibitors and proton pump inhibitors. The concomitant use of these drugs is associated with an increased risk of death.
Areca nut chewing is one of the major risk factors for oral cancer, with large-magnitude risks reported in studies comparing betel quid chewers and never users, and it has been evaluated as a group 1 ...carcinogen by the International Agency for Research on Cancer. Data from a high-quality meta-analysis examining risk estimates are presented in summary form with additional information from more recent studies (pooled adjusted relative risk, 7.9; 95% CI, 7.1 to 8.7). The risk of oral cancer increases in a dose-response manner with the daily number of quids consumed and the number of years chewing. In the Indian subcontinent and in Taiwan, approximately half of oral cancers reported are attributed to betel quid chewing (population attributable fraction, 53.7% for residents in Taiwan and 49.5% for the Indian population), a disease burden that could be prevented. Oral leukoplakia and oral submucous fibrosis are 2 main oral potentially malignant disorders caused by areca nut chewing that can progress to oral cancer with continued use. Ex-chewers seem to demonstrate lower risks than current chewers, but the impact of areca nut cessation on oral cancer risk has not been scientifically evaluated on the basis of randomized controlled studies. These data strongly reconfirm that betel quid chewing, primarily areca nut use, should be taken into account in assessing the cancer risk of South Asian, East Asian populations and Pacific Islanders for the development of oral cancer.
Summary
Background Quantitative analysis of intravenous immunoglobulin (IVIg) treatment against toxic epidermal necrolysis (TEN) is lacking.
Objectives To provide a meta‐analysis evidence‐based ...examination of IVIg efficacy against TEN.
Methods A systematic review and meta‐analysis of literature published before 31 July 2011 was conducted. In observational controlled studies with at least eight patients with TEN receiving IVIg treatment, a pooled estimate of mortality risk was determined, comparing IVIg and supportive care. Statistical analyses were performed on raw data to compare the clinical differences between (i) high‐dose and low‐dose IVIg treatment in adult patients and (ii) paediatric and adult patients treated with IVIg.
Results Seventeen studies met inclusion criteria. Overall mortality rate of patients with TEN treated with IVIg was 19·9%. The pooled odds ratio (OR) for mortality from six observational controlled studies comparing IVIg and supportive care was 1·00 95% confidence interval (CI) 0·58–1·75; P = 0·99. The pooled OR for mortality in patients treated with high‐dose IVIg vs. supportive care was 0·63 (95% CI 0·27–1·44; P = 0·27). Adults treated with high‐dose IVIg exhibited significantly lower mortality than those treated with low‐dose IVIg (18·9% vs. 50%, respectively; P = 0·022); however, multivariate logistic regression model adjustment indicated that IVIg dose does not correlate with mortality (high vs. low dose: OR 0·494; 95% CI 0·106–2·300; P = 0·369). Paediatric patients treated with IVIg had significantly lower mortality than adults (0% vs. 21·6%; P = 0·001).
Conclusions Although high‐dose IVIg exhibited a trend towards improved mortality and children treated with IVIg had a good prognosis, the evidence does not support a clinical benefit of IVIg. Randomized controlled trials are necessary.
See also the Commentary by Walsh and Creamer
The Asteroid Terrestrial impact Last Alert System (ATLAS) system consists of two 0.5 m Schmidt telescopes with cameras covering 29 square degrees at plate scale of 1.86 arcsec per pixel. Working in ...tandem, the telescopes routinely survey the whole sky visible from Hawaii (above δ > − 50 ° ) every two nights, exposing four times per night, typically reaching o < 19 magnitude per exposure when the moon is illuminated and c < 19.5 magnitude per exposure in dark skies. Construction is underway of two further units to be sited in Chile and South Africa which will result in an all-sky daily cadence from 2021. Initially designed for detecting potentially hazardous near earth objects, the ATLAS data enable a range of astrophysical time domain science. To extract transients from the data stream requires a computing system to process the data, assimilate detections in time and space and associate them with known astrophysical sources. Here we describe the hardware and software infrastructure to produce a stream of clean, real, astrophysical transients in real time. This involves machine learning and boosted decision tree algorithms to identify extragalactic and Galactic transients. Typically we detect 10-15 supernova candidates per night which we immediately announce publicly. The ATLAS discoveries not only enable rapid follow-up of interesting sources but will provide complete statistical samples within the local volume of 100 Mpc. A simple comparison of the detected supernova rate within 100 Mpc, with no corrections for completeness, is already significantly higher (factor 1.5 to 2) than the current accepted rates.
In the United States, non-Hispanic Black (NHB), Hispanic, and non-Hispanic American Indian/Alaska Native (NHAIAN) populations experience excess COVID-19 mortality, compared to the non-Hispanic White ...(NHW) population, but racial/ethnic differences in age at death are not known. The release of national COVID-19 death data by racial/ethnic group now permits analysis of age-specific mortality rates for these groups and the non-Hispanic Asian or Pacific Islander (NHAPI) population. Our objectives were to examine variation in age-specific COVID-19 mortality rates by racial/ethnicity and to calculate the impact of this mortality using years of potential life lost (YPLL).
This cross-sectional study used the recently publicly available data on US COVID-19 deaths with reported race/ethnicity, for the time period February 1, 2020, to July 22, 2020. Population data were drawn from the US Census. As of July 22, 2020, the number of COVID-19 deaths equaled 68,377 for NHW, 29,476 for NHB, 23,256 for Hispanic, 1,143 for NHAIAN, and 6,468 for NHAPI populations; the corresponding population sizes were 186.4 million, 40.6 million, 2.6 million, 19.5 million, and 57.7 million. Age-standardized rate ratios relative to NHW were 3.6 (95% CI 3.5, 3.8; p < 0.001) for NHB, 2.8 (95% CI 2.7, 3.0; p < 0.001) for Hispanic, 2.2 (95% CI 1.8, 2.6; p < 0.001) for NHAIAN, and 1.6 (95% CI 1.4, 1.7; p < 0.001) for NHAP populations. By contrast, NHB rate ratios relative to NHW were 7.1 (95% CI 5.8, 8.7; p < 0.001) for persons aged 25-34 years, 9.0 (95% CI 7.9, 10.2; p < 0.001) for persons aged 35-44 years, and 7.4 (95% CI 6.9, 7.9; p < 0.001) for persons aged 45-54 years. Even at older ages, NHB rate ratios were between 2.0 and 5.7. Similarly, rate ratios for the Hispanic versus NHW population were 7.0 (95% CI 5.8, 8.7; p < 0.001), 8.8 (95% CI 7.8, 9.9; p < 0.001), and 7.0 (95% CI 6.6, 7.5; p < 0.001) for the corresponding age strata above, with remaining rate ratios ranging from 1.4 to 5.0. Rate ratios for NHAIAN were similarly high through age 74 years. Among NHAPI persons, rate ratios ranged from 2.0 to 2.8 for persons aged 25-74 years and were 1.6 and 1.2 for persons aged 75-84 and 85+ years, respectively. As a consequence, more YPLL before age 65 were experienced by the NHB and Hispanic populations than the NHW population-despite the fact that the NHW population is larger-with a ratio of 4.6:1 and 3.2:1, respectively, for NHB and Hispanic persons. Study limitations include likely lag time in receipt of completed death certificates received by the Centers for Disease Control and Prevention for transmission to NCHS, with consequent lag in capturing the total number of deaths compared to data reported on state dashboards.
In this study, we observed racial variation in age-specific mortality rates not fully captured with examination of age-standardized rates alone. These findings suggest the importance of examining age-specific mortality rates and underscores how age standardization can obscure extreme variations within age strata. To avoid overlooking such variation, data that permit age-specific analyses should be routinely publicly available.
Abstract
We present analysis of the light curves (LCs) of 77 hydrogen-poor superluminous supernovae (SLSNe I) discovered during the Zwicky Transient Facility Phase I operation. We find that the ...majority (67%) of the sample can be fit equally well by both magnetar and ejecta–circumstellar medium (CSM) interaction plus
56
Ni decay models. This implies that LCs alone cannot unambiguously constrain the physical power sources for an SLSN I. However, 23% of the sample show inverted V-shape, steep-declining LCs or features of long rise and fast post-peak decay, which are better described by the CSM+Ni model. The remaining 10% of the sample favors the magnetar model. Moreover, our analysis shows that the LC undulations are quite common, with a fraction of 18%–44% in our gold sample. Among those strongly undulating events, about 62% of them are found to be CSM-favored, implying that the undulations tend to occur in the CSM-favored events. Undulations show a wide range in energy and duration, with median values (and 1
σ
errors) being as
1.7
%
−
0.7
%
+
1.5
%
E
rad
,
total
and
28.8
−
9.1
+
14.4
days, respectively. Our analysis of the undulation timescales suggests that intrinsic temporal variations of the central engine can explain half of the undulating events, while CSM interaction (CSI) can account for the majority of the sample. Finally, all of the well-observed He-rich SLSNe Ib either have strongly undulating LCs or the LCs are much better fit by the CSM+Ni model. These observations imply that their progenitor stars have not had enough time to lose all of the He-envelopes before supernova explosions, and H-poor CSM are likely to present in these events.
Immune checkpoint inhibitor (ICI) monoclonal antibodies (mAbs) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) or its ligand (PD-L1) produce unique ...toxicity profiles. The objective of this review was to identify patterns and incidence of immune-related adverse events (irAE) based on tumour type and ICI class.
Medline, EMBASE and COCHRANE databases were searched to identify prospective monotherapy trials of ICIs from 2003 to November 2015. Paired reviewers selected studies for inclusion and extracted data. Odds ratio (OR),χ2 tests and multivariable regression models were used to analyse for effect size and associations.
We identified 48 trials (6938 patients), including 26 CTLA-4, 17 PD-1, 2 PD-L1 trials, and 3 studies tested both CTLA-4 and PD-1. Grade 3/4 irAE were more common with CTLA-4 mAbs compared with PD-1 (31% versus 10%). All grades colitis (OR 8.7, 95% CI 5.8–12.9), hypophysitis (OR 6.5, 95% CI 3.0–14.3) and rash (OR 2.0, 95% CI 1.8–2.3) were more frequent with CTLA-4 mAbs; whereas pneumonitis (OR 6.4, 95% CI 3.2–12.7), hypothyroidism (OR 4.3, 95% CI 2.9–6.3), arthralgia (OR 3.5, 95% CI 2.6–4.8) and vitiligo (OR 3.5, 95% CI 2.3–5.3) were more common with PD-1 mAbs. Comparison of irAE from the three most studied tumour types in PD-1 mAbs trials melanoma (n = 2048), non-small-cell lung cancer (n = 1030) and renal cell carcinoma (n = 573) showed melanoma patients had a higher frequency of gastrointestinal and skin irAE and lower frequency of pneumonitis.
CTLA-4 and PD-1 mAbs have distinct irAE profiles. Different immune microenvironments may drive histology-specific irAE patterns. Other tumour-dependent irAE profiles may be identified as data emerge from ICI trials.
Background
Axillary osmidrosis can lead to personal and social problems, particularly in Asian culture. Superficial liposuction with curettage and subcutaneous laser are surgical intervention ...commonly used for osmidrosis.
Objective
Retrospectively, we compared the effectiveness and complications between superficial liposuction with curettage and subcutaneous laser in an Asian population.
Methods
Totally, 66 and 19 patients receiving subcutaneous laser and superficial liposuction with curettage (LC) were recruited. The effectiveness of treatment was assessed by patients subjectively. Recurrence rate of osmidrosis and complications were also evaluated.
Results
95% of patients showed good‐to‐excellent improvement in LC group and only 30% of patients showing good‐to‐excellent results in laser group (P < 0.01). Binary logistic regression revealed that the odds ratio of LC was 53.288 (P = 0.006) for >50% improvement in osmidrosis. The recurrence rate was not significantly different (P = 0.139), however, the duration to recurrence of osmidrosis was significantly longer in LC group (P < 0.01). The complication rate was 31% in LC group and 6% in laser group (P < 0.01).
Conclusion
Superficial liposuction with curettage provides more effective treatment with higher complication rates and is possibly suitable for severe patients. For mild‐to‐moderate osmidrosis, or preferring a better cosmetic result or short recovery, subcutaneous laser could be applied.
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