Objectives: Non-pharmaceutical interventions (NPIs) are effective in curbing the spread of severe acute respiratory syndrome coronavirus 2. All US states have adopted NPI policies, but the compliance to these measures and influence of sociopolitical factors on NPI adherence is unknown. NPI adherence may be approximated by personal mobility in a population that is tracked by anonymous mobile phone data. Study design This is a cross-sectional study of state-level mobility changes across the US. Methods State-level mobility was based on anonymous mobile phone data from multiple participating carriers collected by the University of Washington's Institute for Health Metrics and Evaluation ( http://www.healthdata.org ). Pearson's correlation coefficient was used to examine the strength and direction of the relationship between political affiliations and mobility restriction across states. Multivariable linear regression analyses were used to assess other factors that may impact personal travel. Results All states experienced a decline in personal mobility but had varying nadirs ranging from a 34% to a 69% reduction in mobility, which was not temporally related to the timing of state-level NPI measures. There was a statistically significant linear and negative correlation (r = −0.79) between the proportion of Republicans/leaning Republicans and NPI adherence across US states. The negative association between Republicans and NPI adherence was significant even when adjusting for urbanization, proportion of essential workers, population, Gini index, and poverty rates. Conclusions Political orientation affects risk perception, which may contribute to the unwillingness of some individuals to perceive the coronavirus disease 2019 pandemic as a risk and to comply with NPIs. Our results highlight the importance of sociopolitical factors in disease control and emphasize the importance of bipartisan efforts in fighting the pandemic. These results may have implications for the development, dissemination, and communication of public health policies.

Larger research teams are linked to decreasing impact, whereas contributions by international coauthors result in citation gains.

IMPORTANCE Toxic effects of conventional chemotherapy and molecularly targeted cancer therapies are generally well defined and occur at predictable points. By contrast, owing to their heterogeneous manifestations, unpredictable timing, and clinical overlap with other conditions, immune-related adverse events (irAE) may be more difficult to diagnose and characterize. OBJECTIVE To determine concordance of algorithm-driven medical record review by medical oncologists for the characterization of 8 irAE in patients treated with immune checkpoint inhibitors. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of patients treated with immune checkpoint inhibitors at a National Cancer Institute-designated comprehensive cancer center from November 30, 2015, to March 7, 2018. A sample size of 52 patients provided 80% power to distinguish substantial agreement (κ = 0.85) from poor agreement (κ = 0.5) based on the Cohen κ. MAIN OUTCOMES AND MEASURES Interrater agreement of 2 observers in the occurrence and grade of irAE. RESULTS Of 52 patients (32 [61.5%] male; mean [SD] age, 69 [9] years) analyzed, 42 (80.8%) had non-small cell lung cancer and all received anti-programmed cell death 1 or anti-programmed cell death ligand 1 antibodies, with 3 patients (5.8%) receiving combinations with anti-cytotoxic T-lymphocyte antigen 4 antibodies. A median (interquartile range) of 82 (47-180) documents were reviewed per case. There was limited or poor interrater agreement on irAE occurrence (Cohen κ, 0.37-0.64), with the exception of hypothyroidism (κ = 0.8). Weighted κ similarly showed limited or poor agreement for irAE grade (κ = 0.31-0.75). Differences in assessed time of onset ranged from 5 to 188 days. As a control for data availability and access, observers had a high degree of agreement for the exact start date (98%) and end date (96%) of immunotherapy administration, suggesting that information interpretation rather than identification largely accounted for assessment differences. In multivariable analysis, therapy duration (adjusted odds ratio, 4.80; 95% CI, 1.34-17.17; P = .02) and Charlson Comorbidity Index (adjusted odds ratio, 4.09; 95% CI, 1.10-15.18; P = .03) were significantly associated with discordant irAE assessment. CONCLUSIONS AND RELEVANCE These findings underscore critical challenges in assessing the occurrence, type, timing, and severity of irAE. Apart from hypothyroidism (a condition that has a discrete diagnostic laboratory test and few other likely etiologies during immunotherapy treatment), interobserver agreement was poor. Given the importance of accurate and timely assessment of toxic effects for clinical trials and real-world disease management, efforts to improve irAE diagnosis and characterization are needed.

SUMMARY Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but prediction of their benefit is challenging. Neoantigens generated through impaired non-mismatch DNA repair may result in greater ICI activity. By analyzing 1,661 ICI-treated patients, we show that deletions and mutations in nucleotide excision repair (NER) and homologous repair (HR) pathways are predictors of ICI benefit independent of tumor mutation burden and tumor type. NER and HR mutations are also associated with objective response rates to ICIs in esophagogastric and non-small-cell lung cancers. In a cohort of 40,181 unique patients, NER and HR mutations are present in 3.4% and 13.9% of cancers, respectively. These results indicate that NER and HR gene mutations occur in a subpopulation of cancer patients and may aid patient selection for ICI therapy. Assessing NER and HR mutations in the context of other biomarkers may yield powerful predictors of ICI activity across different cancer types.

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