Long-Term Changes of HIV/AIDS Incidence Rate in China and the U.S. Population From 1994 to 2019: A Join-Point and Age-Period-Cohort Analysis

Although HIV caused one of the worst epidemics since the late twentieth century, China and the U.S. has made substantial progress to control the spread of HIV/AIDS. However, the trends of HIV/AIDS incidence remain unclear in both countries. Therefore, this study aimed to highlight the long-term trends of HIV/AIDS incidence by gender in China and the U.S. population. The data were retrieved from the Global Burden of Disease (GBD) database since it would be helpful to assess the impact/role of designed policies in the control of HIV/AIDS incidence in both countries. The age-period-cohort (APC) model and join-point regression analysis were employed to estimate the age-period-cohort effect and the average annual percentage change (AAPC) on HIV incidence. Between 1994 and 2019, we observed an oscillating trend of the age-standardized incidence rate (ASIR) in China and an increasing ASIR trend in the U.S. Despite the period effect in China declined for both genders after peaked in 2004, the age effect in China grew among the young (from 15–19 to 25–29) and the old age groups (from 65–69 to 75–79). Similarly, the cohort effect increased among those born in the early (from 1924–1928 to 1934–1938) and the latest birth groups (from 1979–1983 to 2004–2009). In the case of the U.S., the age effect declined after it peaked in the 25–29 age group. People born in recent birth groups had a higher cohort effect than those born in early groups. In both countries, women were less infected by HIV than men. Therefore, besides effective strategies and awareness essential to protect the young age groups from HIV risk factors, the Chinese government should pay attention to the elderly who lacked family support and were exposed to HIV risk factors.

Incidence and Prognosis of Thyroid Cancer in Children: Based on the SEER Database

Background: Studying the incidence trend and prognosis factors of childhood Thyroid cancer (TC) may better reflect the prevalence of this disease. Objectives: To explore the trends in the incidence of childhood thyroid cancer and the prognosis.Material and Methods: Join-point regression model was used to analyze incidence trend of TC. Cox regression model was applied to explore the survival situation and prognostic factors.Results: The incidence rate of childhood TC increased between 1975 and 2016 from 3.8/million (95%CI: 2.6-5.5) to 11.5/million (95%CI: 9.2-14.1), AAPC = 2.38 (95%CI: 1.98-9.65)) and could be divided into two stages of increasing trends. The incidence rate of Trend1 (1975-2005) increased slowly but Trend2 (2005-2016) increased dramatically. And annual rates of small size tumor (<4cm) and local stage TC in children increased significantly. The overall cumulative survival rate for childhood TC was high up to 97%-99%. Males, the black people, MTC type, distant metastasis, tumor size >= 4 cm, non-primary cancer were the independent risk factors of prognosis of childhood TC.Conclusions and Significance: A contribution of over detection to rising pediatric TC rates might not be able to rule out. Over-treatment to small size and local stage TC in children should be avoided.

Selective perimeter lockdowns in Madrid: a way to bend the COVID-19 curve?

Lockdowns have been widespread used to limit social interaction and bend the epidemic curve. However, their intensity and geographical delimitation have been variable across different countries. Madrid (Spain) implemented perimeter lockdowns in September with the purpose of bending the COVID-19 curve. In this paper we compared, using join point regressions, the evolution of COVID-19 cases in those areas where this intervention was implemented and those where it was not. According to our analysis, the decrease in the epidemic curve started before the impact of the perimeter lockdown could be reflected.

Selective perimeter lockdowns in Madrid: a way to bend the COVID-19 curve?

Lockdowns have been widespread used to limit social interaction and bend the epidemic curve. However, their intensity and geographical delimitation have been variable across different countries. Madrid (Spain) implemented perimeter lockdowns in September with the purpose of bending the COVID-19 curve. In this paper we compared, using join point regressions, the evolution of COVID-19 cases in those areas where this intervention was implemented and those where it was not. According to our analysis, the decrease in the epidemic curve started before the impact of the perimeter lockdown could be reflected.

Trend Dynamics of Thyroid Cancer Incidence among China and the U.S. Adult Population from 1992-2017: A Join-point and Age-Period-Cohort

Purpose: Based on the previously published reports, the incidence of thyroid cancer (TC) has been increasing in the past 25 years, and the reason for the increase is not yet clear. The present study aims to reveal the long-term trends and age–period–cohort effects for the incidence of TC in China and the U.S. from 1992 to 2017.Patients and methods: We examined the trends of TC incidence in the two countries, for the different genders (men/women) in the Global Burden of Disease (GBD 2017). We further used an age-period-cohort model to analyze age-period-cohort effects on TC incidence, and the average annual percentage change (AAPC) of rates was estimated by Join-point regression analysis.Results: TC increased with the age and period. Aging was one of the most influential factors of TC in China. The age effect increased markedly in the U.S. compared with China. The period effect showed an increase in China while that tended to grow steadily during 1992-2017 in the U.S. The cohort effect peaked in 1963-1967 birth cohorts for men and women in China and declined consistently in the birth cohort in the U.S.Conclusion: From 1992 to 2017, due to ionizing radiation and over-diagnosis, age-standardized TC incidence rates in both genders rose in China and the U.S. The standardized incidence rate of women is higher than that of men. It is necessary to provide women with reasonable prevention and protection measures for TC. We need to apply for health services and screening to reduce ionizing radiation.

The Age Distribution among Children Seeking Medical Treatment for Precocious Puberty in Taiwan

Objective: Children with precocious puberty (PP) may have increased physiological and psychological problems. In this study, we aimed to explore the trend of parents seeking medical care for their children with precocious puberty. Methods: The Taiwan National Health Insurance Research Dataset (NHIRD) was used to estimate the prevalence (2000–2013) and incidence (2002–2013) of PP (ICD-9 code: 259.1) among boys aged 0–11 years and girls aged 0–10 years. The proportions of PP management within 1 year from the date of first diagnosis were also compared between two periods (2002–2007 and 2008–2012). The trends of PP prevalence or incidence were determined by join-point regression. Results: In 2000, 309 boys and 2706 girls had at least one visit for PP, the crude prevalence rates (per 10,000 persons) were 0.99 (95% confidence interval, 95% CI 0.87–1.14) and 13.56 (95% CI 13.01–14.13) in boys and girls, respectively. In 2013, the crude prevalence rates increased to 7.01 (95% CI 6.56–7.84) and 110.95 (95% CI 108.97–112.96) in boys and girls, respectively. A total of 2584 girls and 207 boys with incident PP cases were identified in 2002, and 7498 girls and 739 boys were identified in 2013. For girls, the incidence rates (per 10,000 person-years) were 16.17 (95% CI 15.55–16.80) and 70.23 (95% CI 68.65–71.83) in 2002 and 2013, respectively. For boys, the incidence rates were 1.09 (95% CI 0.95–1.24) and 5.72 (95% CI 5.32–6.15) in 2002 and 2013, respectively. The sex ratio (F:M) of the incidence of PP cases was 14.89 in 2002 and 12.28 in 2013. Conclusion: In this study, from 2000 to 2013, the frequency of visiting pediatric endocrinology outpatient clinics for precocious puberty increased in both genders. We advocate that it is important to pay increased attention to children’s health, environmental hormones, and diet. Researchers should consider how to survey precocious puberty and offer parents more education to avoid the waste of medical resources or delays in seeking medical care.

"Dr. Google" consultations on psoriasis: trends and seasonality in a digital era. (Preprint)

BACKGROUND In recent years, the Internet has become an essential tool where people seek information about health care. OBJECTIVE The aim of this study is to use data from Google Trends to analyze worldwide public interest in psoriasis and its different treatment modalities, and to analyze the possible seasonality of searches. METHODS A worldwide search was carried out through Google Trends from 2004 to 2019. A combination of terms related to psoriasis treatments was introduced. Join-point regression has been performed. Google Trends assigns a relative search volume index to the search terms. Comparison annual relative search volume, annual percentage change, and average annual percentage change (AAPC) were analyzed to assess loss or gain of interest. RESULTS Our study reflects an increase interest in secukinumab (AAPC: 33.7), ixekizumab (AAPC: 23.3) and apremilast (AAPC: 21.4). It shows less interest in methotrexate (AAPC: -3.6), retinoids (AAPC: -9.8), cyclosporine (AAPC: -9.8), phototherapy (AAPC: -6.3), etanercept (AAPC: -14.9), infliximab (AAPC: -14) and adalimumab (AAPC: -5.8). Seasonality was found in the search term “psoriasis”. CONCLUSIONS Secukinumab followed by ixekizumab, and apremilast have been the treatments that have aroused the most interest. Our results show current psoriasis search trends and its different treatments based on Google trend analysis.

Spatio-Temporal Clustering of Childhood Leukemia Relative to Population Mixing in Finland: A Nationwide Register-Based Study

Introduction Leukemia is the most common malignant disease of the childhood. Its etiology remains unclear apart from Down syndrome and high-dose ionizing radiation. Involvement of immunological factors is plausible, and it was proposed by Leo Kinlen that population influx into a rural site could cause an increase in childhood leukemia incidence, by introducing an infectious agent into a pediatric population spared from it at younger, more typical age1. Also, Spatio-temporal clusters of childhood leukemia have been observed in some studies for example around nuclear power plants and some have been related to specific subtypes2. Evidence regarding both population mixing and clustering remains conflicting and requires further clarification. In this study, we aim to characterize these intertwined phenomena with Finnish high-quality register-based data. Materials and Methods We identified all childhood leukemia cases diagnosed in 1990-2011 in Finland (N=1093) and three times as many individually matched (on sex and the year of birth) controls. From population register center, we obtained complete residential histories for all subjects, including the coordinates of the dwellings, as well as the moving dates. In this study, the date of diagnosis was the main time point of interest and no latency period was used. We obtained annual citizenship numbers from Statistics Finland for each Finnish municipality to quantify the annual influx and efflux of people in those areas. We used join-point regression to identify counties with the potentially leukemogenic migration patterns as suggested by Kinlen. We analyzed both absolute influx to the municipality, and migration relative to the population size. A doubling (100% increase) from the municipality's pre-existing stable influx rate was defined as an event of interest. The municipalities and the years with the recognized migration pattern were aggregated for better statistical power. For spatiotemporal clustering, we used Knox's test with predefined thresholds for closeness of two events in time (6, 12, 18 and 24 months) and in Euclidean distance (0.5, 1, 2, 5 and 10 kilometers). ETV6-RUNX1 subtype was analyzed separately in accordance with the findings of a recent study2. We also created a bootstrapping-based method for computing distributions for the expected number of cases for each municipality and year and searched for instances of significant excesses. In addition, we evaluated the case-control status the nearest neighbor of each subject and compared the observed distribution of cases and controls to the expected. Results Using Knox's test, a significant excess of clustering was observed for thresholds of 5 km and 6 months, (p=0.047) but when corrected for multiple testing, it was no longer significant. For the ETV6-RUNX1 subtype, we found no indications of clustering, unlike in the Swiss study (lowest p-value of 0.61 before correcting for multiple testing)2. When analyzing the nearest neighbors of the cases, the ratio between cases and controls did not differ from the expected 1/4 for the closest (0.24, p=0.39) or for five neighbors (0.24, p=0.49). Using join-point regression we were able to identify counties with high influx of people into rural areas. In the bootstrapping analysis, we observed two instances when the 95th percentile of the expected number was exceeded by more than 2 cases in a municipality during one year. The absolute annual incidence in both counties was four cases. Discussion Using multiple methods, we did not find clear evidence for clustering of childhood leukemia in Finland. The use of small units of area might have diluted our results to some degree, as the number of expected cases was low even in the municipalities of Finland. However, the methods that did not require pre-specified areal units did not reveal any clustering either. In future, we will further develop our approach regarding the join-point approach, as the primary analyses showed some weak signals. Also, different methods for recognizing areas of interest will be used. Also clustering methods utilizing subjects' entire residential histories could improve the sensitivity to detect clustering. Figure - An example of a Finnish municipality (Liminka), in which an influx to a rural site has been recognized using join-point regression Kinlen LJ. Br J Cancer. 2012. Kreis C et al. PLoS One. 2017. Figure Disclosures No relevant conflicts of interest to declare.

Trends in Early Mortality from Multiple Myeloma (MM): A Population-Based Analysis

Background: Survival of patients with MM has improved significantly over recent years due to therapeutic advancements. Population-level data has shown that a substantial proportion of MM patients may die early after their diagnosis and real-world evidence regarding early mortality (≤6 months after MM diagnosis) has been conflicting. We evaluated the trends, causes and predictors of early mortality among newly diagnosed MM (NDMM) patients in the real world. Methods: We used Surveillance Epidemiology and End Results (SEER) database, to identify all adult patients (age ≥ 18 years) who were diagnosed of MM from 1975 to 2015. Data on age, gender, geographical regions, year of diagnosis, survival time, vital status at 6 months after diagnosis and cause of death (COD) were extracted. Ages were categorized as quartiles while period of diagnosis for multivariate analysis were categorized by running a joinpoint analysis separately for the all-cause and myeloma-specific mortality. To look at trends in early mortality, we estimated proportion of deaths for each year and plotted it as a scatterplot against the year of diagnosis and fitted it in the join point regression model by applying the NCI's Join point Regression Program, Version 4.5.0.1. By this method we identified the year(s) when a trend change was produced, calculated the annual percentage change (APC) in rates between trend-change points, and the average annual percentage change (AAPC) in the whole period studied. To correct for known errors with COD attribution, we applied a special COD variable which has been recently developed by the SEER program to indicate if the death was due to the primary cancer diagnosis or other causes. A multivariate analysis was conducted to analyze the predictors of all-cause and myeloma-specific mortality within 6 months by fitting into logistic regression model. Results: Of 90,975 NDMM patients, early mortality due to any cause was noted in 18,810 (20.7%). For the whole cohort, median age was 68 years, majority of the patients were males (53.1%), of non-Hispanic white (NHW) race/ethnicity (65.5%) and were diagnosed in SEER registries in the western region (53.9%). An overall survival (OS) of ≤6 months was seen for approximately 22% of NHW but 18% of non-Hispanic blacks (NHB) and Hispanics. OS of ≤6 months was seen in 10% of patients in the first quartile of age (&lt;60 years) as compared to 36% of patients in the 4th quartile (≥78 years). By geographical regions, 23.3% of MM patients in the Midwest had ≤6-month OS as compared to only 18.4% in the Northeast. The most common early mortality COD was MM in 74.7% of the patients, followed by cardiovascular (11.9%), other (8.8%) and infectious causes (3.1%). The overall pattern of COD at 6 months was similar to COD at any time in the whole cohort. Joinpoint regression analysis of trends data resulted in 1 joinpoint for all-cause 6-month mortality while 2 joinpoints were noticed for myeloma-specific mortality (Figure 1). A steep decline in mortality was noticed in the more recent time periods for both, all-cause (2006-2015) and myeloma-specific (2003-2015) mortality rates with an AAPC of 3.93 (95%CI p&lt;0.001) for all-cause and 3.95 (95%CI p&lt;0.001) for myeloma-specific mortality. Prior to 2006, the decrease in all-cause mortality was only modest whereas decrease in myeloma-specific mortality witnessed a sharp decline from 1975-1987 as well. On MVA, advanced age (p&lt;0.001), NHW race/ethnicity and Midwest geographic region (p&lt;0.001) were associated with higher likelihood of mortality while female gender (p&lt;0.001), more recent period of diagnosis (p&lt;0.001), and "other" races (not NHW, NHB or Hispanics) (p&lt;0.001) were associated with lower risk of mortality. Conclusion: Our results show that early mortality due to MM remains high despite therapeutic improvements and there are significant gender, racial and geographic disparities for this phenomenon. However, significant declines in all-cause and MM-specific early mortality in the more recent times are promising. The risk of early mortality is higher among men, older patients, NHW and Midwest region. A focus on interventions to reduce early mortality, including early diagnosis, use of efficacious anti-MM therapy and aggressive supportive care should be directed at groups with high-risk for early mortality from MM. Disclosures Chanan-Khan: Millennium: Research Funding; Ascentage: Research Funding; AbbVie: Research Funding; Xencor: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Jansen: Research Funding; Mayo Clinic: Employment. Ailawadhi:Celgene: Consultancy; Pharmacyclics: Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy; Cellectar: Research Funding; Janssen: Consultancy, Research Funding.