Impact of Prioritizing Elderly and High-risk Individuals During COVID-19 Vaccine Allocation

BackgroundThe prioritization of vaccine eligibility for different subpopulations is an important decision to curb spread and severe outcomes of epidemic infectious diseases for which vaccines become available. Using COVID-19 as a prototype, this study evaluates the public health impact of various vaccine prioritization schemes of elderly and high-risk individuals with different vaccination start dates and rollout speeds. MethodsAn agent-based simulation model was adapted and used to project the number of infections, hospitalizations, and deaths under various vaccination start dates, rollout speeds, and prioritization schemes, including (A)no prioritization, (B)two-staged prioritization of elderly population, and (C)multi-staged prioritization of elderly and then high-risk population. The study period was February 18th, 2020 –June 1st, 2021, and the state of Georgia was used as a case study. ResultsThe relative effectiveness of the prioritization schemes depends on the outcome considered, as well as the vaccination start date, prioritized subpopulations, and rollout speed. Having no prioritization results in the fewest infections and hospitalizations in most scenarios; however, it yields the highest number of deaths. Prioritizing the elderly and then high-risk individuals results in the fewest overall and high-risk deaths in most scenarios. ConclusionsHaving no vaccine prioritization, i.e., opening vaccination to every adult regardless of age, simplifies vaccine rollout and reduces the infection spread but results in a higher number of deaths, especially among the elderly and high-risk populations. Prioritizing the elderly, then high-risk patients, as opposed to prioritizing only the elderly provides benefit regarding severe outcomes; however, such assumed benefits need to be counterbalanced with challenges in communicating eligibility and criteria and in distributing vaccines effectively and equitably which could result in suboptimal vaccine uptake and coverage, including among people within subpopulations at disproportionate risk of illness, hospitalization and death, of particular concern during periods of high incidence, severe disease, and death.

Survival Outcomes Associated with First and Second-Line Palliative Systemic Therapies in Patients with Metastatic Bladder Cancer

Background: Real-world data on palliative systemic therapies (PST) in treating metastatic bladder cancer (mBC) is limited. This study investigates current trends in treating mBC with first- (1L) and second-line (2L) chemotherapy (CT) and immunotherapy (IT). Methods: A chart review was conducted on patients diagnosed with stage II-IV bladder cancer in 2014–2016. Survival outcomes were compared between chemotherapy, immunotherapy, and supportive care. Results: out of 297 patients, 77% were male. 44% had stage IV disease at diagnosis. Median age at metastasis was 73 years. 40% of patients received 1L PST and 34% received 2L PST. Median overall survival (mOS) was longer in those receiving PST versus no treatment (p < 0.001). Patients receiving CT and IT sequentially had the longest mOS (18.99 months). First-line IT and CT mOS from treatment start dates were 5.03 and 9.13 months, respectively (p = 0.81). Gemcitabine with cisplatin (8.88 months) or carboplatin (9.13 months) were the most utilized 1L chemotherapy regimens (p = 0.85). 2L IT and CT mOS from treatment start dates were 6.72 and 3.78 months, respectively (p = 0.15). Conclusion: real-world mOS of >1.5 years in mBC is unprecedented and supports using multiple lines of PST. Furthermore, immunotherapy may be a comparable alternative to chemotherapy in both 1L and 2L settings.

Visual Arts: Postmodernism

Postmodernism is notoriously difficult to define in any concise manner. Its start dates (and end dates, for that matter) exist in a state of flux, often varying by decades in the historiographies of major disciplines. In an attempt to begin to understand postmodernism, many theorists, art historians, and philosophers choose to take a rather apophatic approach by describing that which it is not, namely starting by understanding modernism. After all, that is embedded into the term postmodernism itself; at its core, postmodernism is connected to modernism. Essentially, modernism as a movement was predicated upon an avant-gardism that envisioned modern art as the cure-all for the broken world, working toward a utopian ideal. In understanding art’s engagement with religion in the postmodern era, it is also necessary to consider the shifting social landscape of institutional religion and politics at this time. The culture wars of the end of the 20th century both shaped and were shaped by postmodern art, with famous clashes between artists and the emerging religious right and/or prominent political figures dominating the headlines. Largely because of these events, many critical narratives have promoted the idea that art and religion had little to do with each other in this period. While secularization theories are gradually unraveling in the field at large, these ideas still figure prominently in many discussions of modernism and postmodernism. Regardless, artists have continued to engage with religious subject matter throughout the 20th and 21st centuries. The appearance of secularization is imperative to note, particularly as a number of postmodern artists (indeed, some of the most recognizable names in the art world) have engaged with religion in their work. This is not to say that postmodern artworks with religious themes all celebrate religion uncritically, nor do they all examine religion from outside the realm of belief in a strictly anthropological manner. One of the main difficulties in interpreting postmodernism’s rather vexed relationship with institutional religion is the multivalence of many of the artworks. Multiplicity of meaning in both artistic intent (if such a thing is granted) and reception is common in postmodernism, which should caution critics from attempting to make concrete assertions about any presence of pure religiosity or pure secularism. Trends in postmodern artistic practices, such as the mixing of high and low art forms and media, the use of appropriation, pastiche, institutional critique, and more, along with the increasing diversification of artists and contexts, have resulted in the examination of religious subjects in ways that are particularly postmodern.

Analysis of changes in Betula pollen season start including the cycle of pollen concentration in atmospheric air

Birch belongs to the most important allergenic taxa in Europe, therefore information on the start dates of the pollen season is very important for allergists and their patients as well as for climatologists. The study examined changes in the start of the birch pollen season as well as determined the trend of these changes. Pollen monitoring was performed in Lublin (eastern Poland) in the period 2001–2019 using the volumetric method. The Makra-test was used to detect periods with significantly higher or lower average of the onset than the average for the whole dataset. Two significant falls in the average of the pollen season start were found in 2007 and 2014. Besides, taking into account the 2-3-year rhythm of high and low concentrations of birch pollen in the atmospheric air, linear trends were fitted for the subsets of high and low abundance seasons. Significant changes in Betula pollen season start dates were only determined for the highly abundance seasons, while the results for seasons with a low concentration did not allow rejecting the hypothesis about the lack of a linear trend in the changes in the studied parameter. Moreover, a significant polynomial relationship was found between the beginning of a pollen season and the average values of monthly temperatures preceded a season. These analyses show that the start dates of the Betula pollen season are getting significantly earlier. The dynamics of changes differ between seasons with high and low concentrations of pollen.

Subtle influence of the Atlantic Meridional Overturning Circulation (AMOC) on seasonal sea surface temperature (SST) hindcast skill in the North Atlantic

We investigate the impact of the strength of the Atlantic Meridional Overturning Circulation (AMOC) at 26∘ N on the prediction of North Atlantic sea surface temperature anomalies (SSTAs) a season ahead. We test the dependence of sea surface temperate (SST) predictive skill in initialised hindcasts on the phase of the AMOC at 26∘N, invoking a seesaw mechanism driven by AMOC fluctuations, with positive SSTAs north of 26∘ N and negative SSTAs south of 26∘ N after a strong AMOC and vice versa. We use initialised simulations with the MPI-ESM-MR (where MR is mixed resolution) seasonal prediction system. First, we use an assimilation experiment between 1979–2014 to confirm that the AMOC leads a SSTA dipole pattern in the tropical and subtropical North Atlantic, with the strongest AMOC fingerprints after 2–4 months. Going beyond previous studies, we find that the AMOC fingerprint has a seasonal dependence and is sensitive to the length of the observational window used, i.e. stronger over the last decade than for the entire time series back to 1979. We then use a set of ensemble hindcast simulations with 30 members, starting each February, May, August and November between 1982 and 2014. We compare the changes in skill between composites based on the AMOC phase a month prior to each start date to simulations without considering the AMOC phase and find subtle influence of the AMOC mechanism on seasonal SST prediction skill. We find higher subtropical SST hindcast skill at a 2–4-month lead time for June–July–August (JJA) SSTA composites based on the AMOC phase at May start dates than for the full time period. In other regions and seasons, we find a negligible impact of the AMOC seesaw mechanism on seasonal SST predictions due to atmospheric influence, calling for caution when considering such a mechanism. Our method shows that, for May start dates following strong AMOC phases, summer SST hindcast skill over the subtropics increases significantly compared to that of weak AMOC phases. This suggests that in the assessment of SST skill for a season ahead an eye should be kept on the initial AMOC state.

50 Years of Pollen Monitoring in Basel (Switzerland) Demonstrate the Influence of Climate Change on Airborne Pollen

Climate change and human impact on vegetation modify the timing and the intensity of the pollen season. The 50 years of pollen monitoring in Basel, Switzerland provide a unique opportunity to study long-term changes in pollen data. Since 1969, pollen monitoring has been carried out in Basel with a Hirst-type pollen trap. Pollen season parameters for start dates, end dates and duration were calculated with different pollen season definitions, which are commonly used in aerobiology. Intensity was analyzed by the annual pollen integral (APIn), peak value and the number of days above specific thresholds. Linear trends were calculated with the non-parametric Mann Kendall method with a Theil-Sen linear trend slope. During the last 50 years, linear increase of the monthly mean temperatures in Basel was 0.95–1.95°C in the 3 winter months, 2–3.7°C in spring months and 2.75–3.85°C in summer months. Due to this temperature increase, the start dates of the pollen season for most of the spring pollen species have advanced, from 7 days for Poaceae to 29 days for Taxus/Cupressaceae. End dates of the pollen season depend on the chosen pollen season definition. Negative trends predominate, i.e., the pollen season mostly ends earlier. Trends in the length of the pollen season depend even more on the season definitions and results are contradictory and often not significant. The intensity of the pollen season of almost all tree pollen taxa increased significantly, while the Poaceae pollen season did not change and the pollen season of herbs decreased, except for Urticaceae pollen. Climate change has a particular impact on the pollen season, but the definitions used for the pollen season parameters are crucial for the calculation of the trends. The most stable results were achieved with threshold definitions that indicate regular occurrence above certain concentrations. Percentage definitions are not recommended for trend studies when the annual pollen integral changed significantly.

POS0648 SURVIVAL ANALYSIS OF TIME TO FIRST ADVERSE DRUG REACTION AND DRUG SURVIVAL IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH METHOTREXATE AND HYDROXYCHLOROQUINE MONOTHERAPIES OR COMBINATION THERAPY

Background:Methotrexate (MTX) and hydroxychloroquine (HCQ) are first line treatments of rheumatoid arthritis (RA). Adverse drug reactions (ADRs) during treatment with these drugs are common. Survival analysis on time to first ADR and on first time drug use duration have not yet been performed for these drugs in real-world settings.Objectives:To compare proportions of patients with ADRs during first time use of either MTX monotherapy, HCQ monotherapy or MTX+HCQ combination therapy and to compare survival to first ADR and drug survival between these drugs.Methods:Retrospective single centre cohort study including adult RA patients treated with either MTX monotherapy, HCQ monotherapy or MTX+HCQ combination therapy. First time users between 1 January 2003 and 30 April 2020 were followed until discontinuation of their first time drug use. The proportion of patients with ADRs was defined as the percentage of patients experiencing an ADR during their first time drug use. Survival to first ADR and drug survival of first time drug use were also assessed. MTX+HCQ use was considered combination therapy when the start dates of these drugs differed less than 14 days. For both monotherapies, end of first time drug use was defined as drug discontinuation for more than 90 days. For MTX+HCQ combination therapy, end of first time drug use was defined as discontinuation of either MTX, HCQ or both for more than 90 days. Differences in the proportion of patients experiencing an ADR during first time drug use of MTX, HCQ or a combination of both was statistically tested using Fisher’s Exact Test. Survival to first ADR and drug survival were studied by Kaplan-Meier analysis and statistically tested by performing Log Rank tests.Results:In total, 794 patients were included (MTX 363, HCQ 77, MTX+HCQ 354). For 156 patients (19.6%) at least one ADR was registered during first time drug use (MTX 59 [16.3%], HCQ 9 [11.7%], MTX+HCQ 88 [24.9%]). Proportions of ADRs differed significantly between MTX monotherapy and MTX+HCQ combination therapy (p=0.005) and between HCQ monotherapy and MTX+HCQ combination therapy (p=0.011). Survival to first ADR also differed significantly for both monotherapies compared to MTX+HCQ combination therapy (medians not reached, p<0.001 and p<0.008, respectively (figure 1A)). Drug survival differed significantly between MTX and HCQ monotherapy and between MTX monotherapy and MTX+HCQ combination therapy (median survival MTX 3.32 years (95% CI [2.81-3.83]; HCQ 1.39 years (95% CI [1.03-1.75]); MTX+HCQ 1.23 years (95% CI [1.11-1.34]), both p<0.001 (figure 1B)).Figure 1.Kaplan-Meier curves of MTX and HCQ monotherapies and MTX+HCQ combination therapy, with (a) survival to first ADR and (b) drug survival.Conclusion:Patients using MTX+HCQ combination therapy are more likely to experience an ADR during the first time drug use compared to MTX and HCQ monotherapies. MTX+HCQ combination therapy also leads to experiencing an ADR sooner compared to both monotherapies. Drug survival of patients treated with HCQ monotherapy as well as MTX+HCQ combination therapy is shorter compared to MTX monotherapy.Disclosure of Interests:Kimberly Velthuis: None declared, My Nguyen: None declared, Joep Scholl: None declared, Jurriaan Jansen: None declared, Jette van Lint: None declared, Peter ten Klooster: None declared, Harald Vonkeman Consultant of: BMS, Celgene, Celltrion, Galapagos, Gilead, Janssen-Cilag, Lilly, Novartis, Pfizer, Sanofi-Genzyme, Grant/research support from: Abbvie, Naomi Jessurun: None declared

A First Pre-season Pollen Transport Climatology to Bavaria, Germany

Climate impacts on the pollen season are well-described however less is known on how frequently atmospheric transport influences the start of the pollen season. Based on long-term phenological flowering and airborne pollen data (1987–2017) for six stations and seven taxa across Bavaria, Germany, we studied changes in the pollen season, compared pollen and flowering season start dates to determine pollen sources, and analyzed the likelihood of pollen transport by HYSPLIT back trajectories. Species advanced their pollen season more in early spring (e.g., Corylus and Alnus by up to 2 days yr−1) than in mid spring (Betula, Fraxinus, Pinus); Poaceae and Artemisia exhibited mixed trends in summer. Annual pollen sums mainly increased for Corylus and decreased for Poaceae and Artemisia. Start of pollen season trends largely deviated from flowering trends, especially for Corylus and Alnus. Transport phenomena, which rely on comparisons between flowering and pollen dates, were determined for 2005–2015 at three stations. Pre-season pollen was a common phenomenon: airborne pollen was predominantly observed earlier than flowering (median 17 days) and in general, in 63% of the cases (except for Artemisia and Poaceae, and the alpine location) the pollen sources were non-local (transported). In 54% (35%) of these cases, back trajectories confirmed (partly confirmed) the pre-season transport, only in 11% of the cases transport modeling failed to explain the records. Even within the main pollen season, 70% of pollen season start dates were linked to transport. At the alpine station, non-local pollen sources (both from outside Bavaria as well as Bavarian lowlands) predominated, in only 13% of these cases transport could not be confirmed by back trajectories. This prominent role of pollen transport has important implications for the length, the timing, and the severity of the allergenic pollen season, indicating only a weak dependency on flowering of local pollen sources.

Yearly evolution of Euro-Atlantic weather regimes and of their sub-seasonal predictability

It is often assumed that weather regimes adequately characterize atmospheric circulation variability. However, regime classifications spanning many months and with a low number of regimes may not satisfy this assumption. The first aim of this study is to test such hypothesis for the Euro-Atlantic region. The second one is to extend the assessment of sub-seasonal forecast skill in predicting the frequencies of occurrence of the regimes beyond the winter season. Two regime classifications of four regimes each were obtained from sea level pressure anomalies clustered from October to March and from April to September respectively. Their spatial patterns were compared with those representing the annual cycle. Results highlight that the two regime classifications are able to reproduce most part of the patterns of the annual cycle, except during the transition weeks between the two periods, when patterns of the annual cycle resembling Atlantic Low regime are not also observed in any of the two classifications. Forecast skill of Atlantic Low was found to be similar to that of NAO+, the regime replacing Atlantic Low in the two classifications. Thus, although clustering yearly circulation data in two periods of 6 months each introduces a few deviations from the annual cycle of the regime patterns, it does not negatively affect sub-seasonal forecast skill. Beyond the winter season and the first ten forecast days, sub-seasonal forecasts of ECMWF are still able to achieve weekly frequency correlations of r = 0.5 for some regimes and start dates, including summer ones. ECMWF forecasts beat climatological forecasts in case of long-lasting regime events, and when measured by the fair continuous ranked probability skill score, but not when measured by the Brier skill score. Thus, more efforts have to be done yet in order to achieve minimum skill necessary to develop forecast products based on weather regimes outside winter season.