Clinical Pathology - Research Publications
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ItemEndpoint surrogacy in oncology Phase 3 randomised controlled trials(SPRINGERNATURE, 2020-08-04)Endpoint surrogacy is an important concept in oncology trials. Using a surrogate endpoint like progression-free survival as the primary endpoint-instead of overall survival-would lead to a potential faster drug approval and therefore more cancer patients with an earlier opportunity to receive the newly approved drugs.
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ItemGeneralizability of COVID-19 Mortality Risk Score Model.(Elsevier, 2020-12)It is with deep appreciation that we read the research by Yu et al.1 investigating the risk factors for mortality among 1,663 patients hospitalized with the novel coronavirus disease 2019 (COVID-19) in a Wuhan (China) hospital that utilized clinical characteristics in the development of a statistical model that predicts death risk.1 Given that the ongoing pandemic has placed great pressure on healthcare systems worldwide, we consider prediction models to be of high utility in assessing which patients with COVID-19 have higher mortality risk to optimize healthcare resources.
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ItemInfant mortality and risk factors in Nigeria in 2013-2017: A population-level study(Elsevier, 2022-09)BACKGROUND: Globally, over the past two decades, many countries have significantly reduced the rate of infant mortality. Yet, in Africa, Nigeria remains one of the countries with the highest infant mortality rate (IMR). METHODS: We conducted a population-level study using the 2018 Nigeria Demographic Health Survey (NDHS). A total of 41,668 household data were analyzed retrospectively. The association between each exposure and infant mortality was analyzed in logistic regression models (independently adjusted by demographic and socioeconomic status variables) and confirmed by the multiple comparisons analysis. FINDINGS: The overall IMR of 2013-2017 was 61.5 (95% CI 58.0, 65.3) per 1000 live births. In general, the North-West and North-East regions had the highest IMR, whereas the South-West, South-East and South-South regions had the lowest IMR. The regression analysis found women who delivered their babies at the age <=18 years old (odds ratio (OR): 1.37 [1.17, 1.62]), had religion of Islam (OR: 1.35 [1.10, 1.65]), no ANC visit (OR: 1.69 [1.21, 2.35]), >4 ANC visits (OR: 1.70 [1.23, 2.34]), ANC not at home or skilled provider (0.40 [0.35, 0.46]) and the babies as the first child (OR: 1.23 [1.07, 1.42]) to be associated with higher IMR. INTERPRETATION: Our findings imply that Nigeria is not on track to achieving the SDG target of reducing child mortality by 2030. Sustainable interventions are urgently needed to address the challenges for women of reproductive age, particularly those that are living in the rural areas and Northern regions, having limited/no access to health care/skilled providers, and delivered their first child. FUNDING: None.
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ItemThe global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019(ELSEVIER SCIENCE INC, 2022-01)BACKGROUND: In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. METHODS: Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. FINDINGS: There were 1·19 million (95% UI 1·11-1·28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59·6 [54·5-65·7] per 100 000 person-years) and high-middle SDI countries (53·2 [48·8-57·9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14·2 [12·9-15·6] per 100 000 person-years) and middle SDI (13·6 [12·6-14·8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23·5 million (21·9-25·2) DALYs to the global burden of disease, of which 2·7% (1·9-3·6) came from YLDs and 97·3% (96·4-98·1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. INTERPRETATION: Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. FUNDING: Bill & Melinda Gates Foundation, American Lebanese Syrian Associated Charities, St Baldrick's Foundation, and the National Cancer Institute.
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ItemPokémon GO! GO! GO! The impact of Pokémon GO on physical activity and related health outcomes(AME Publishing, 2021-07-20)Many previous studies have established that a sedentary lifestyle is associated with the risks of disease incidence as well as mortality (1-3). In fact, the World Health Organization (WHO) considered physical inactivity as a leading factor for global mortality (4). In 2013, the WHO proposed the Global Action Plan [2013–2020], aiming to prevent and control noncommunicable diseases; one of the targets is to reduce 10% of relative prevalence of insufficient physical activity by 2025 (5). This is in consideration of the threat from physical inactivity as well as a high prevalence of physical inactivity and sedentary behaviors (6,7), but also in addition to strong evidence suggesting that the risks of incidence (8) and mortality (9,10) can be reduced by decreasing sedentary time especially when physical activity is improved.
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ItemResearch priorities to reduce the impact of COVID-19 in low- and middle-income countries(INT SOC GLOBAL HEALTH, 2022)BACKGROUND: The COVID-19 pandemic has caused disruptions to the functioning of societies and their health systems. Prior to the pandemic, health systems in low- and middle-income countries (LMIC) were particularly stretched and vulnerable. The International Society of Global Health (ISoGH) sought to systematically identify priorities for health research that would have the potential to reduce the impact of the COVID-19 pandemic in LMICs. METHODS: The Child Health and Nutrition Research Initiative (CHNRI) method was used to identify COVID-19-related research priorities. All ISoGH members were invited to participate. Seventy-nine experts in clinical, translational, and population research contributed 192 research questions for consideration. Fifty-two experts then scored those questions based on five pre-defined criteria that were selected for this exercise: 1) feasibility and answerability; 2) potential for burden reduction; 3) potential for a paradigm shift; 4) potential for translation and implementation; and 5) impact on equity. RESULTS: Among the top 10 research priorities, research questions related to vaccination were prominent: health care system access barriers to equitable uptake of COVID-19 vaccination (ranked 1st), determinants of vaccine hesitancy (4th), development and evaluation of effective interventions to decrease vaccine hesitancy (5th), and vaccination impacts on vulnerable population/s (6th). Health care delivery questions also ranked highly, including: effective strategies to manage COVID-19 globally and in LMICs (2nd) and integrating health care for COVID-19 with other essential health services in LMICs (3rd). Additionally, the assessment of COVID-19 patients' needs in rural areas of LMICs was ranked 7th, and studying the leading socioeconomic determinants and consequences of the COVID-19 pandemic in LMICs using multi-faceted approaches was ranked 8th. The remaining questions in the top 10 were: clarifying paediatric case-fatality rates (CFR) in LMICs and identifying effective strategies for community engagement against COVID-19 in different LMIC contexts. INTERPRETATION: Health policy and systems research to inform COVID-19 vaccine uptake and equitable access to care are urgently needed, especially for rural, vulnerable, and/or marginalised populations. This research should occur in parallel with studies that will identify approaches to minimise vaccine hesitancy and effectively integrate care for COVID-19 with other essential health services in LMICs. ISoGH calls on the funders of health research in LMICs to consider the urgency and priority of this research during the COVID-19 pandemic and support studies that could make a positive difference for the populations of LMICs.
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ItemThe global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019(ELSEVIER SCIENCE INC, 2022-08-20)BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01-4·94) deaths and 105 million (95·0-116) DALYs for both sexes combined, representing 44·4% (41·3-48·4) of all cancer deaths and 42·0% (39·1-45·6) of all DALYs. There were 2·88 million (2·60-3·18) risk-attributable cancer deaths in males (50·6% [47·8-54·1] of all male cancer deaths) and 1·58 million (1·36-1·84) risk-attributable cancer deaths in females (36·3% [32·5-41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6-28·4) and DALYs by 16·8% (8·8-25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9-42·8] and 33·3% [25·8-42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. FUNDING: Bill & Melinda Gates Foundation.
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ItemPan-Driver-Negatives versus Epidermal Growth Factor Receptor Mutants for C-Stage IA Lung Adenocarcinoma with Ground-Glass Opacity(Editorial Committee of Annals of Thoracic and Cardiovascular Surgery, 2022)Purpose: We aimed to verify the prognosis of epidermal growth factor receptor (EGFR) mutation of clinical (c)-stage IA lung adenocarcinoma with the ground-glass opacity (GGO) component. Methods: We evaluated 226 cases of surgically resected c-stage IA lung adenocarcinoma with GGO component. Endpoints were overall survival (OS) and recurrence-free survival (RFS). Kaplan–Meier analysis and the log-rank test were used to estimate the survival differences. Prognostic factors were assessed using the univariable and multivariable Cox proportional hazards model. Results: Among the 226 cases, 177 cases harbored the EGFR-mutant adenocarcinoma with the GGO component. The mean duration of follow-up time was 54.4 ± 1.2 months. The 5-year OS and RFS did not differ significantly between the EGFR-mutant and wild-type groups (5-year OS 100% vs. 94.3%, hazard ratio [HR] 0.276, P = 0.168; 5-year RFS 94.7% vs. 95.7%, HR 0.873, P = 0.864). Multivariable Cox hazard model revealed that radiologically solid component size (P = 0.010) and pathological node-positive (P = 0.036) were significant predictors of an inferior RFS. Conclusion: EGFR-mutant was not a prognostic factor of OS and RFS for c-stage IA lung adenocarcinoma with the GGO component. Radiologically solid component size and pathological lymph node status were independent prognostic factors of worse RFS.
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ItemGlobal trends in the burden of esophageal cancer, 1990-2019: results from the Global Burden of Disease Study 2019.(AME Publishing Company, 2023-02-28)BACKGROUND: Esophageal cancer is one of the leading causes of cancer death worldwide. A deeper understanding of the trends in annual incidence, mortality, and disability-adjusted life-years (DALYs) of esophageal cancer is critical for management and prevention. In this study, we report on the disease burden of esophageal cancer in 204 countries and territories between 1990 and 2019 by age, sex, and sociodemographic index (SDI). METHODS: Data on incidence, mortality, and DALYs were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The estimated numbers and age-standardized rates for esophageal cancer in 2019 are presented in this paper, as well as trends from 1990 to 2019. All estimates are presented as counts and age-standardized rates per 100,000 population, with 95% uncertainty intervals (UIs) for each estimate. RESULTS: In 2019, nearly 535,000 (95% UI: 467,000-595,000) new cases of esophageal cancer occurred globally. Esophageal cancer was responsible for more than 498,000 (95% UI: 438,000-551,000) deaths and 11.7 million (95% UI: 10.4-12.9 million) DALYs. Worldwide age-standardized rates of esophageal cancer, including incidence, deaths, and DALYs, have declined since 1990. However, the trends differ across countries and territories. Notably, there was a nonlinear but generally inverse correlation between age-standardized DALY rates and SDI. Higher age-standardized incidence and death rates were observed in males compared to females, and both increased with age. Regarding risk factors, smoking, alcohol use, and high body-mass index were 3 predominant contributors to esophageal cancer DALYs in 2019 for both sexes worldwide. CONCLUSIONS: This study found a global reduction in the esophageal cancer burden, but substantial heterogeneity remains across regions and countries. Hence, the identification of high-risk groups and the exploration of specific local strategies and primary prevention efforts are required.