Cancer incidence and mortality trends in Asia based on regions and human development index levels: an analyses from GLOBOCAN 2020.

OBJECTIVE: As Asian countries transition socially and economically to higher Human Development Index (HDI) levels, cancer trends are expected to shift to those seen in the Western World. A strong correlation also exists between HDI levels and age-standardized rates (ASR) for the incidence and mortality of cancer. However, there are very few reports on the trends in Asian countries, particularly in Low and Middle-Income Countries (LMICs). In this study, we have investigated the relationship between socioeconomic developments in Asia (determined using HDI levels of countries) and cancer incidence and mortality in these nations. METHODS: The GLOBOCAN 2020 database was used to study the cancer incidence and mortality data for all cancers combined and those most commonly diagnosed in Asia. The difference in data was analyzed based on region and HDI level. Further, the predictions for cancer incidence and mortality in 2040 according to the GLOBOCAN 2020 were analyzed using the updated HDI stratification described in the UNDP 2020 report. RESULTS: Asia has the highest cancer burden compared to the other regions worldwide. Lung cancer carries the highest cancer incidence and mortality rates in the region. Inequitable distribution of cancer incidence and mortality is seen across regions and HDI levels in Asia. CONCLUSIONS: Inequalities in cancer incidence and mortality can only be expected to increase unless innovative and cost-effective interventions are urgently implemented. An effective cancer management plan is needed in Asia, particularly in LMICs, prioritizing effective cancer prevention and control measures for health systems.

A framework for setting enrollment goals to ensure participant diversity in sponsored clinical trials in the United States.

BACKGROUND: Diversity in clinical trials (CTs) has the potential to improve health equity and close health disparities. Underrepresentation of historically underserved groups compromises the generalizability of trial findings to the target population, hinders innovation, and contributes to low accrual. The aim of this study was to establish a transparent and reproducible process for setting trial diversity enrollment goals informed by the disease epidemiology. METHOD: An advisory board of epidemiologists with expertise in health disparities, equity, diversity, and social determinants of health was convened to evaluate and strengthen the initial goal-setting framework. Data sources used were the epidemiologic literature, US Census, and real-world data (RWD); limitations were considered and addressed where appropriate. A framework was designed to safeguard against the underrepresentation of historically medically underserved groups. A stepwise approach was created with Y/N decisions based on empirical data. RESULTS: We compared race and ethnicity distributions in the RWD of six diseases from Pfizer's portfolio chosen to represent different therapeutic areas (multiple myeloma, fungal infections, Crohn's disease, Gaucher disease, COVID-19, and Lyme disease) to the distributions in the US Census and established trial enrollment goals. Enrollment goals for potential CTs were based on RWD for multiple myeloma, Gaucher disease, and COVID-19; enrollment goals were based on the Census for fungal infections, Crohn's disease, and Lyme disease. CONCLUSIONS: We developed a transparent and reproducible framework for setting CT diversity enrollment goals. We note how limitations due to data sources can be mitigated and consider several ethical decisions in setting equitable enrollment goals.

Outcomes in patients with lung cancer treated with crizotinib and erlotinib in routine clinical practice: A post-authorization safety cohort study conducted in Europe and in the United States.

PURPOSE: We examined safety outcomes of interest (SOI) and overall survival (OS) among lung cancer patients initiating crizotinib and erlotinib in routine clinical practice. METHODS: This descriptive cohort study used routinely collected health data in Denmark, Finland, Sweden, the Netherlands, and the United States (US) during 2011-2017, following crizotinib commercial availability in each country. Among crizotinib or erlotinib initiators, we reported baseline characteristics and incidence rates and cumulative incidences of the SOI - hepatotoxicity, pneumonitis/interstitial lung disease, QT interval prolongation-related events, bradycardia, vision disorders, renal cysts, edema, leukopenia, neuropathy, photosensitivity, malignant melanoma, gastrointestinal perforation, cardiac failure and OS. Results from the European Union (EU) countries were combined using meta-analysis; results from the US were reported separately. RESULTS: There were 456 patients in the crizotinib cohort and 2957 patients in the erlotinib cohort. Rates of the SOI per 1000 person-years in the crizotinib cohort ranged from 0 to 65 in the EU and from 0 to 374 in the US. Rates of the SOI per 1000 person-years in the erlotinib cohort ranged from 0 to 91 in the EU and from 3 to 394 in the US. In the crizotinib cohort, 2-year OS was ~50% in both EU and US. In the erlotinib cohort, 2-year OS was 21% in the EU and 35% in the US. CONCLUSIONS: This study describes clinical outcomes among lung cancer patients initiating crizotinib or erlotinib in routine clinical practice. Differences between SOI rates in EU and US may be partially attributable to differences in the underlying databases.

Classification and characteristics of on-label and off-label apixaban use in Denmark and Sweden.

PURPOSE: To estimate the proportion of apixaban users who received the drug for on-label indications and characterise the patients using apixaban for on-label and off-label indications. METHODS: We report results from two independently conducted studies in Denmark and Sweden, with 19,709 Danish and 17,592 Swedish patients, who received at least one outpatient dispensing of apixaban as identified through nationwide prescription registries. Indications, inferred from inpatient and hospital diagnoses recorded at the initial apixaban dispensing, were classified as on-label, off-label, or unclassified according to the Summary of Product Characteristics. All diagnoses were retrieved using inpatient or outpatient hospital diagnoses at the first outpatient dispensing during the study period. RESULTS: Men comprised 52% of the users in both Denmark and Sweden. The median age was 76 years (interquartile range [IQR]: 68-83 years) among Danish patients and 74 years (IQR: 67-82 years) among Swedish patients. An on-label indication could be assigned to 82.6% (95% confidence interval [CI]: 82.1%-83.1%) of the Danish patients and 86.4% (95% CI: 85.9%-86.9%) of the Swedish patients. The main on-label indication for apixaban was non-valvular atrial fibrillation (NVAF), which accounted for 76.1% of the indications in Denmark and 69.1% of the indications in Sweden. Off-label indications were assigned to 10.8% (95% CI: 10.3-11.2) of the Danish patients (main indication possible mechanical heart valve) and 7.7% (95% CI: 7.3-8.1) of the Swedish patients (main indication off-label atrial fibrillation). CONCLUSION: The majority of apixaban initiators in Denmark and Sweden received apixaban for an on-label indication, primarily for NVAF.

An Implementation and Visualization of the Tree-Based Scan Statistic for Safety Event Monitoring in Longitudinal Electronic Health Data.

INTRODUCTION: Longitudinal electronic healthcare data hold great potential for drug safety surveillance. The tree-based scan statistic (TBSS), as implemented by the TreeScan® software, allows for hypothesis-free signal detection in longitudinal data by grouping safety events according to branching, hierarchical data coding systems, and then identifying signals of disproportionate recording (SDRs) among the singular events or event groups. OBJECTIVE: The objective of this analysis was to identify and visualize SDRs with the TBSS in historical data from patients using two antifungal drugs, itraconazole or terbinafine. By examining patients who used either itraconazole or terbinafine, we provide a conceptual replication of a previous TBSS analyses by varying methodological choices and using a data source that had not been previously used with the TBSS, i.e., the Optum Clinformatics™ claims database. With this analysis, we aimed to test a parsimonious design that could be the basis of a broadly applicable method for multiple drug and safety event pairs. METHODS: The TBSS analysis was used to examine incident events and any itraconazole or terbinafine use among US-based patients from 2002 through 2007. Event frequencies before and after the first day of drug exposure were compared over 14- and 56-day periods of observation in a Bernoulli model with a self-controlled design. Safety events were classified into a hierarchical tree structure using the Clinical Classifications Software (CCS) which mapped International Classification of Diseases, 9th Revision (ICD-9) codes to 879 diagnostic groups. Using the TBSS, the log likelihood ratio of observed versus expected events in all groups along the CCS hierarchy were compared, and groups of events that occurred at disproportionally high frequencies were identified as potential SDRs; p-values for the potential SDRs were estimated with Monte-Carlo permutation based methods. Output from TreeScan® was visualized and plotted as a network which followed the CCS tree structure. RESULTS: Terbinafine use (n = 223,968) was associated with SDRs for diseases of the circulatory system (14- and 56-day p = 0.001) and heart (14-day p = 0.026 and 56-day p = 0.001) as well as coronary atherosclerosis and other heart disease (14-day p = 0.003 and 56-day p = 0.004). For itraconazole use (n = 36,025), the TBSS identified SDRs for coronary atherosclerosis and other heart disease (p = 0.002) and complications of an implanted or grafted device (14-day p = 0.001 and 56-day p < 0.05). Use of both drugs was associated with SDRs for diseases of the digestive system at 14 days (p < 0.05) and this SDR had been observed among terbinafine users in a previous TBSS analysis with a different data source. The TreeScan® visualization facilitated the identification of the atherosclerosis and other heart disease SDRs as well as highlighting the consistency of the SDR for diseases of the digestive system across drugs and data sources. CONCLUSION: With the TBSS, we identified potential SDRs related to the circulatory system that may reflect the cardiac risk that was described in the itraconazole product label. SDRs for diseases of the digestive system among terbinafine users were also reported in a previous signal detection analysis, although other SDRs from the previous publications were not replicated. The TBSS visualizations aided in the understanding and interpretation of the TBSS output, including the comparisons to the previous publications. In this conceptual replication, differences in the results observed in our analysis and the previous analyses could be attributable to variation in modeling and design choices as well as factors that were intrinsic to the underlying data sources. The broad consistency, but far from perfect concordance, of our results with the known safety profile of these antifungals including the risks from the itraconazole product label supports the rationale for continued investigations of signal detection methods across differing data sources and populations.

Disparities in influenza mortality and transmission related to sociodemographic factors within Chicago in the pandemic of 1918.

Social factors have been shown to create differential burden of influenza across different geographic areas. We explored the relationship between potential aggregate-level social determinants and mortality during the 1918 influenza pandemic in Chicago using a historical dataset of 7,971 influenza and pneumonia deaths. Census tract-level social factors, including rates of illiteracy, homeownership, population, and unemployment, were assessed as predictors of pandemic mortality in Chicago. Poisson models fit with generalized estimating equations (GEEs) were used to estimate the association between social factors and the risk of influenza and pneumonia mortality. The Poisson model showed that influenza and pneumonia mortality increased, on average, by 32.2% for every 10% increase in illiteracy rate adjusted for population density, homeownership, unemployment, and age. We also found a significant association between transmissibility and population density, illiteracy, and unemployment but not homeownership. Lastly, analysis of the point locations of reported influenza and pneumonia deaths revealed fine-scale spatiotemporal clustering. This study shows that living in census tracts with higher illiteracy rates increased the risk of influenza and pneumonia mortality during the 1918 influenza pandemic in Chicago. Our observation that disparities in structural determinants of neighborhood-level health lead to disparities in influenza incidence in this pandemic suggests that disparities and their determinants should remain targets of research and control in future pandemics.

Short-term malaria reduction by single-dose azithromycin during mass drug administration for trachoma, Tanzania.

Single-dose mass drug administration of azithromycin (AZT) is underway to eliminate trachoma worldwide. Studies in Ethiopia showed a reduction in all-cause childhood deaths after administration. To examine the effect of single-dose AZ MDA on prevalent malaria infections in a large prospective cohort of children and parents in Dodoma Province, Tanzania, we quantified the temporal prevalence of malaria parasitemia by real-time PCR for 6 months after single-dose AZT. In the first month after treatment but not in subsequent months, Plasmodium falciparum infections were reduced by 73% (95% CI 43%-89%) in treatment versus control villages and differences remained significant (p = 0.00497) in multivariate models with village-level random effects. Genetic sequencing of P. falciparum ribosomal L4 protein showed no mutations associated with AZT resistance. AZT mass drug administration caused a transient, 1-month antimalarial effect without selecting for P. falciparum ribosomal L4 resistance mutations in a region with a 10-year history of treating trachoma with this drug.

Proximity to vacant buildings is associated with increased fire risk in Baltimore, Maryland, homes.

BACKGROUND: Fires and burns are a leading cause of unintentional injury death in the USA. Although it has been anecdotally reported that vacant dwellings are at a higher risk for fire, the association between vacancy and fire risk at the individual household level has not been empirically measured. METHODS: In this cross-sectional study, geocoded residential vacant properties (VP) and fire events are analysed in Baltimore City at the census tract level and the individual household level. RESULTS: On average, a 10% increase in the proportion of vacancies in a census tract was associated with a 9.9% increase in fires (95% CI: 5% to 15%). Random-effects Poisson models, controlling for housing and neighbourhood conditions, found contagion effects. The risk of fire in an occupied dwelling increased by 8% (95% CI: 1% to 10%) for every vacant structure within 10 m, and the risk of fire decreased by half (95% CI: 45% to 62%) for every km between an occupied dwelling and vacant building. Close proximity to VP was associated with trash fires within dwellings (p=0.039) and structure fires (p=0.012). CONCLUSIONS: We believe that this is the first study to demonstrate increased risk posed by nearby VP at the household level, confirming earlier ecological analyses of the role of VP as strong correlates of home fires. Measurement of this risk can motivate property owners, policy makers and insurers to invest in risk reduction measures that include building maintenance and trash removal.

Prevalence and density-related concordance of three diagnostic tests for malaria in a region of Tanzania with hypoendemic malaria.

Accurate malaria diagnosis has dual roles in identification of symptomatic persons for effective malaria treatment and also enumeration of asymptomatic persons who contribute to the epidemiologic determinants of transmission. Three currently used diagnostic tests, microscopy, rapid diagnostic tests (RDTs), and real-time PCR, all have different sensitivities and specificities, which are parasite density dependent. Here, we compare their concordance among 451 febrile episodes in a cohort of 2,058 children and adults followed over 6 months in a region in central Tanzania with hypoendemic malaria. Microscopy, a histidine-rich protein-based RDT, and two different real-time PCR gene probes detected Plasmodium falciparum in 20, 54, 41, and 78 episodes of fever, respectively. They had complete concordance in only 9 episodes. Real-time PCR with an 18S probe was more sensitive than with a mitochondrial probe for cytochrome b despite higher copy numbers of mitochondrial DNA. Both PCR yields were increased 4-fold by glycogen/acetate precipitation with low-speed centrifugation. Duplicate PCR increases low-density malaria detection. RDT had the highest number of unique positives, presumably from persistent antigen despite the absence of parasites, although RDT did not detect 3 parasitemias with over 1,000 parasites/µl. In a latent class analysis, real-time PCR had significantly higher sensitivity than did microscopy or RDT. Agreement between real-time PCR, RDT, and microscopy was highest in March and April, when both the P. falciparum parasite rate and parasite densities are highest. Real-time PCR is more sensitive and specific than RDT and microscopy in low-prevalence, low-parasite-density settings.