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Background: The objective of this study was to explore the abilities of atezolizumab plus chemotherapy in preventing brain metastases (BMs) among metastatic non–small cell lung cancer (NSCLC) without initial BMs, as well as the risk factors of BMs. Methods: Individual patient data from three trials involving first‐line atezolizumab for metastatic NSCLC (IMpower130, IMpower131, and IMpower150) were pooled. Among patients without baseline BMs and without epidermal growth factor receptor (EGFR) and/or anaplastic lymphoma kinase (ALK) mutations, those receiving atezolizumab + chemotherapy ± bevacizumab were classified as the atezolizumab plus chemotherapy group and those receiving placebo + chemotherapy ± bevacizumab were classified as the chemotherapy group. The cumulative incidences of BM (CI‐BMs) between the two groups were compared. Other factors associated with the CI‐BM were analyzed by Cox regression analyses. Results: With a median follow‐up of 17.6 months (range, 0.03–33.64 months), 74 (3.1%) of the 2380 enrolled patients developed BMs, including 50 (3.1%) and 24 (3.0%) in the atezolizumab plus chemotherapy group (n = 1589) and the chemotherapy group (n = 791), respectively. The CI‐BMs at 6, 12, and 24 months were 1.7%, 2.8%, and 3.3%, respectively. After taking competing risk events into account, there was no significant difference in the CI‐BMs between the two groups (p =.888). Nevertheless, the use of bevacizumab and the histology of nonsquamous NSCLC were found to be independently associated with the risk of BMs. Conclusions: In patients with metastatic EGFR/ALK wild‐type NSCLC without baseline BMs, adding atezolizumab in the first‐line treatment might not reduce the CI‐BM. However, the administration of bevacizumab may reduce the risk of BMs. In patients with metastatic EGFR/ALK wild‐type non–small cell lung cancer without baseline brain metastases (BMs), adding atezolizumab in the first‐line treatment could not reduce the cumulative incidence of BM. However, administration of bevacizumab may reduce the risk of BMs. [ABSTRACT FROM AUTHOR]

Background: The global COVID-19 pandemic has resulted in over seven million deaths, and IFI can further complicate the clinical course of COVID-19. Coinfection of COVID-19 and IFI (secondary IFI) pose significant threats not only to healthcare systems but also to patient lives. After the control measures for COVID-19 were lifted in China, we observed a substantial number of ICU patients developing COVID-19-associated IFI. This creates an urgent need for predictive assessment of COVID-19 patients in the ICU environment for early detection of suspected fungal infection cases. Methods: This study is a single-center, retrospective research endeavor. We conducted a case-control study on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients. The cases consisted of patients who developed any secondary IFI during their ICU stay at Jilin University China-Japan Union Hospital in Changchun, Jilin Province, China, from December 1st, 2022, to August 31st, 2023. The control group consisted of SARS-CoV-2 positive patients without secondary IFI. Descriptive and comparative analyses were performed, and a logistic regression prediction model for secondary IFI in COVID-19 patients was established. Additionally, we observed an increased incidence of COVID-19-associated pulmonary aspergillosis (CAPA) during this pandemic. Therefore, we conducted a univariate subgroup analysis on top of IFI, using non-CAPA patients as the control subgroup. Results: From multivariate analysis, the prediction model identified 6 factors that are significantly associated with IFI, including the use of broad-spectrum antibiotics for more than 2 weeks (aOR=4.14, 95% CI 2.03-8.67), fever (aOR=2.3, 95%CI 1.16-4.55), elevated log IL-6 levels (aOR=1.22, 95% CI 1.04-1.43) and prone position ventilation (aOR=2.38, 95%CI 1.15-4.97) as independent risk factors for COVID-19 secondary IFI. High BMI (BMI = 28 kg/m²) (aOR=0.85, 95% CI 0.75-0.94) and the use of COVID-19 immunoglobulin (aOR=0.45, 95% CI 0.2-0.97) were identified as independent protective factors against COVID-19 secondary IFI. The Receiver Operating Curve (ROC) area under the curve (AUC) of this model was 0.81, indicating good classification. Conclusion: We recommend paying special attention for the occurrence of secondary IFI in COVID-19 patients with low BMI (BMI < 28 kg/m²), elevated log IL-6 levels and fever. Additionally, during the treatment of COVID-19 patients, we emphasize the importance of minimizing the duration of broad-spectrum antibiotic use and highlight the potential of immunoglobulin application in reducing the incidence of IFI. [ABSTRACT FROM AUTHOR]

Serosurveys are a key resource for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) population exposure. A growing body of evidence suggests that asymptomatic and mild infections (together making up over 95% of all infections) are associated with lower antibody titers than severe infections. Antibody levels also peak a few weeks after infection and decay gradually. We developed a statistical approach to produce estimates of cumulative incidence from raw seroprevalence survey results that account for these sources of spectrum bias. We incorporate data on antibody responses on multiple assays from a postinfection longitudinal cohort, along with epidemic time series to account for the timing of a serosurvey relative to how recently individuals may have been infected. We applied this method to produce estimates of cumulative incidence from 5 large-scale SARS-CoV-2 serosurveys across different settings and study designs. We identified substantial differences between raw seroprevalence and cumulative incidence of over 2-fold in the results of some surveys, and we provide a tool for practitioners to generate cumulative incidence estimates with preset or custom parameter values. While unprecedented efforts have been launched to generate SARS-CoV-2 seroprevalence estimates over this past year, interpretation of results from these studies requires properly accounting for both population-level epidemiologic context and individual-level immune dynamics.

Post-graduate students and faculty usually conduct case-control studies. However, sometimes they conduct cohort studies that are short-duration. Most investigators enroll the participants in two groups according to the exposure. Then, follow the participants for some duration. At the end of the study, relative risk is calculated, and the work is published in some journal. The exposure may be one time, which may or may not be quantified. The follow-up duration may not be participant-specific, and differential follow-up does not exist. The author has given three examples: the first example of consanguineous marriages and congenital disabilities, the second example of the ABO blood group system and childhood asthma, and the third example of insecticide spraying and stillbirth. In the given examples, cumulative or density incidence cannot be calculated in a true sense and, therefore, risk ratio. Even estimating the incidence of outcome variables in some studies is not appropriate. Risk ratio calculation in such scenarios is questionable because exposure quantification, follow-up period, and combination are the limiting factors. In case-control studies, the prevalence ratio is calculated, which is analogous to relative risk. The author suggests that, in such circumstances, prevalence ratio calculation will be more appropriate.

Data on retrospective compensation claims for injuries caused by pharmaceutical drugs are prone to selection and reporting biases. Nevertheless, this case study of the antidiabetic drug benfluorex shows that such data can be used to estimate the cumulative incidence of drug‐related injury, and to provide insights into its epidemiology. To this end, we develop a modelling framework for under‐reporting of retrospective claims for compensation arising from drug damage. The model involves a longitudinal component related to attrition of cases over time, and a cross‐sectional component related to incomplete reporting. We apply this model to cardiac valve surgery necessitated by exposure to benfluorex. Benfluorex was marketed in France between 1976 and 2009, when it was withdrawn because it caused valvular heart disease. A scandal erupted in 2010 over the scale of the damage caused by the drug. Since then, no further estimates of cumulative incidence have been published, though thousands of claims for compensation have been processed. The analysis combines compensation claims data and sociological survey data on benfluorex users, together with data on benfluorex sales and duration of treatment. We find a threshold of toxicity at about 6 months' exposure, and that at least 1690 individuals (95% CI 1290 to 2320) needed heart surgery to replace or repair valves damaged by exposure to benfluorex in France: a cumulative incidence of 3.68 per 10,000 (95% CI 2.68 to 5.34) benfluorex users or 3.22 per 10,000 (95% CI 2.48 to 4.39) person‐years at risk above the exposure threshold. While these findings are tentative, they are consistent with those obtained previously using very different methods. [ABSTRACT FROM AUTHOR]

Aims: We aimed to describe and compare the incidence of the first cardiovascular event and its major subtypes, coronary heart disease (CHD), cerebrovascular disease, heart failure (HF), or peripheral artery disease (PAD), according to age and sex in a population-based cohort of individuals with type 2 diabetes (T2D) from a Mediterranean region. Material and methods: We used linked primary care electronic medical reports, pharmacy-invoicing data, and hospital admission disease registry records from the SIDIAP database, which contains linked data for 74% of the Catalonian population. We selected individuals with T2D aged 30 to 89 years free of cardiovascular disease (CVD). The primary outcome was the first presentation of CVD. Results: The study cohort included 247,751 individuals (48.6% women, 66.8 ± 11.9 years). During a 6.99-year follow-up, the cumulative incidence of the first cardiovascular event was 23.4%. Men were at higher risk for CVD (hazard ratio [HR]: 1.47 95%CI: 1.45-1.50), CHD (HR: 1.52 95%CI: 1.47-1.57), cerebrovascular disease (HR:1.07 95%CI: 1.03-1.10) and PAD (HR: 2.30 95%CI: 2.21-2.39) than women but at a lower risk for HF (HR:0.70 95%CI: 0.68-0.73). CHD and PAD were the most frequent CVD presentations among men (28.1% and 27.5%) and HF (40.1%) in women. CHD predominated among young participants of both sexes, while HF predominated among women older than 65 and men older than 75. Conclusions: In individuals with T2D, the overall risk and the type of first CVD manifestation largely varied by sex and age. This epidemiological evidence should be considered in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Human immunodeficiency virus (HIV) / acquired immunodeficiency syndrome (AIDS) infection has been a serious health problem in pediatric age groups globally, and especially in African countries such as Angola. Our aim was to determine the prevalence rate, accumulate incidence rate, and mortality rate of HIV/AIDS infection in children under 14 years of age residing in four municipalities of Malanje (Malanje, Cacuso, Calandula, and Caculama), from 2010 to 2021. Methodology: This was a documentary research study, with data from 2010 to 2021, developed from a sample size of 10,984 children. Results: The prevalence rate data showed a certain level of dispersion, and no relationship was identified in its behavior over the years (R² = 0.0036). On the other hand, the accumulate incidence rate presented a tendency to decrease, indicating a moderate level of correlation in its behavior over the years (R² = 0.4278). Finally, the mortality rate has been decreasing and presented a high correlation in its association with the years under analysis (R² = 0.8142). Primary schooling and low purchasing power were frequent (60% and 82%, respectively) among the families of HIV-infected children under study. Conclusions: Despite the temporal variation of HIV in children under 14 years of age living in the different municipalities, there was a tendency of its diminishing in the later part of the period, from 2010 to 2021. Nevertheless, the key players should focus on strengthening community strategies for prevention, investigation, and diagnosis of HIV infections in this population. [ABSTRACT FROM AUTHOR]

Serosurveys are a widely used tool to estimate the cumulative incidence—the fraction of a population that has been infected by a given pathogen. These surveys rely on serological assays that measure the level of pathogen-specific antibodies. Because antibody levels are waning, the fraction of previously infected individuals that have seroreverted increases with time past infection. To avoid underestimating the true cumulative incidence, it is therefore essential to correct for waning antibody levels. We present an empirically supported approach for seroreversion correction in cumulative incidence estimation when sequential serosurveys are conducted in the context of a newly emerging infectious disease. The correction is based on the observed dynamics of antibody titers in seropositive cases and validated using several in silico test scenarios. Furthermore, through this approach we revise a previous cumulative incidence estimate relying on the assumption of an exponentially declining probability of seroreversion over time, of severe acute respiratory syndrome coronavirus 2, of 76% in Manaus, Brazil, by October 2020 to 47.6% (95% confidence region: 43.5–53.5). This estimate has implications, for example, for the proximity to herd immunity in Manaus in late 2020. [ABSTRACT FROM AUTHOR]

In this paper, an empirical model with the critical number of incidences and deaths for female cancers as adjustable parameters has been developed using life expectancy data from GLOBOCAN world estimates on cancer types. The model was developed based on the cumulative risk and exponential correlation techniques such that the significance of the adjustable parameters ascertains the strength of this research in two ways. First, it indicates indicates the rapid increase in female cancer morbidity with increase in the number of male cancer cases, regardless of incidence or mortality. Second, it suggests that female cancer cases may approach a virtual limiting value as male cancer cases reach extremely high levels. This projection aligns with the global population trends, indicating a proportional increase in cancer cases each year. Additionally, the cumulative risk of cancer incidences of each sex has been modelled separately against the global cumulative risk of cancer incidences of both sexes which revealed regions that have passed their inflection point and those that are yet to reach the inflection point. There was a curvature change, which indicates an inflection point coinciding with the South-Eastern Region and indicating that for the regions beyond the inflection point, the increase of the cumulative risk of cancer incidences of females against that of males is more accentuated compared with the regions before the inflection point. However, when the cumulative risk of cancer mortality of each sex is modelled separately against the global cumulative risk of cancer mortality of both sexes shows a non-linear dependence and the increase is more accentuated for males than for females. This finding indicates that cumulative risk is influenced by factors beyond the male-female population ratio. This study advances cancer studies as it provides a nuanced understanding of gender-specific cancer trends, crucial for developing targeted cancer prevention and treatment strategies. By elucidating the dynamics of cancer incidences and mortalities across different regions and sexes, the findings can inform public health policies and resource allocation to combat cancer more effectively on a global scale.

Healthcare workers (HCW) have been the professional category most exposed to SARS-CoV-2. The pandemic’s impact on HCW was analyzed in terms of COVID-19-related temporary disability (TD) between February 15th, 2020 and May 1st, 2021. TDs in HCW for COVID-19 infection or quarantine were described. TD quarantine/infection ratios and TDs per 100,000 affiliated HCW were compared with the cumulative incidence (CI) of COVID-19 cases notified to the National Network of Epidemiological Surveillance. TDs rates by economic activity and occupation were computed. A total of 429,127 TDs were recorded, 36,6% for infection. Three-quarters (76%) were women. The median TD quarantine/infection ratio was 2.5 (Interquartile range [IQR] 1.5–3.9). TDs rates in HCW were always above the CI except for the last two months of the fourth wave. Hospital activities accounted for 84% of TDs and showed the highest TD rate for infection (8,279/100,000). Nursing professionals and midwifery, Physicians, and Nursing assistants accounted for 26, 18 and 17 % of the conceded TD respectively, whereas the highest TDs rates were registered among Nursing assistants, Nursing professionals and Physicians: 7,426, 6,925 and 5,508/100,000, respectively. The results indicate the high impact of COVID-19 on HCW in Spain and it’s inequalities. They also confirm that TDs represent a complementary source of information for epidemiological and public health surveillance and could provide an early warning of new emerging infections.

Post-graduate students and faculty usually conduct case-control studies. However, sometimes they conduct cohort studies that are short-duration. Most investigators enroll the participants in two groups according to the exposure. Then, follow the participants for some duration. At the end of the study, relative risk is calculated, and the work is published in some journal. The exposure may be one time, which may or may not be quantified. The follow-up duration may not be participant-specific, and differential follow-up does not exist. The author has given three examples: the first example of consanguineous marriages and congenital disabilities, the second example of the ABO blood group system and childhood asthma, and the third example of insecticide spraying and stillbirth. In the given examples, cumulative or density incidence cannot be calculated in a true sense and, therefore, risk ratio. Even estimating the incidence of outcome variables in some studies is not appropriate. Risk ratio calculation in such scenarios is questionable because exposure quantification, follow-up period, and combination are the limiting factors. In case-control studies, the prevalence ratio is calculated, which is analogous to relative risk. The author suggests that, in such circumstances, prevalence ratio calculation will be more appropriate. [ABSTRACT FROM AUTHOR]

Abstract Background Gastric cancer (GC) constitutes a major global health problem, of which remnant gastric cancer (RGC) occurs less frequently. The rate of RGCs after gastrectomy for GC is increasing recently due to improved survival and screening, however, their incidence and risk have not been reported in the U.S. population. The objective of this study was to evaluate the incidence and elevated risk of RGC after GC gastrectomy in this population, and to identify the risk factors. Methods Patients underwent gastrectomy for first primary GC in 2000–2015 and those who developed RGC were identified from Surveillance, Epidemiology and End Results (SEER) database. Fine-Gray regression was used to estimate the cumulative incidence and to identify risk factors. Standardized incidence ratios (SIRs) were calculated by Poisson regression to compare the risk with the general population. Results Among 21,566 patients included in the cohort, 227 developed RGC. The 20-year cumulative incidence of RGC was 1.88%. Multivariate analysis revealed that older age, invasion depth, male sex, marital status, and lower income are independent risk factors for RGC development. SIR was 7.70 overall and > 4.5 in each stratum. Conclusions Cumulative incidence and risk for RGCs increased continuously in patients underwent GC gastrectomy. Close and lifelong endoscopy surveillance should be recommended for patients who received GC gastrectomy, especially those with high-risk factors.

Background: Although endoscopic submucosal dissection (ESD) provides a high rate of curative resection, the remaining gastric mucosa after ESD is at risk for metachronous superficial gastric epithelial neoplasms (MSGENs). It leaves room for risk factors for developing MSGENs after ESD. This study aimed to identify clinicopathological risk factors for the occurrence of MSGENs, and to evaluate the association of Helicobacter pylori (H. pylori) with the MSGENs. Methods: We conducted a retrospective cohort study including 369 patients with 382 lesions that underwent ESD for adenoma/early gastric cancer. Results: Twenty-seven MSGENs occurred. The subjects were divided into MSGEN and not-MSGEN groups. There was a significantly higher frequency of histological intestinal metaplasia (HIM) and initial neoplasm location in the upper or middle parts (INUM) in the MSGEN group. The HIM and INUM groups had a significantly higher cumulative incidence of MSGENs. We compared 27 patients from the MSGEN group and 27 patients from the not-MSGEN group that were matched to the MSGEN group for variables including HIM and INUM. There was a significantly higher frequency of the spontaneous disappearance of H. pylori in the MSGEN group. Conclusions: HIM, INUM, and the spontaneous disappearance of H. pylori may be clinicopathological risk factors for developing MSGENs after ESD. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) constitutes a major global health problem, of which remnant gastric cancer (RGC) occurs less frequently. The rate of RGCs after gastrectomy for GC is increasing recently due to improved survival and screening, however, their incidence and risk have not been reported in the U.S. population. The objective of this study was to evaluate the incidence and elevated risk of RGC after GC gastrectomy in this population, and to identify the risk factors. Methods: Patients underwent gastrectomy for first primary GC in 2000–2015 and those who developed RGC were identified from Surveillance, Epidemiology and End Results (SEER) database. Fine-Gray regression was used to estimate the cumulative incidence and to identify risk factors. Standardized incidence ratios (SIRs) were calculated by Poisson regression to compare the risk with the general population. Results: Among 21,566 patients included in the cohort, 227 developed RGC. The 20-year cumulative incidence of RGC was 1.88%. Multivariate analysis revealed that older age, invasion depth, male sex, marital status, and lower income are independent risk factors for RGC development. SIR was 7.70 overall and > 4.5 in each stratum. Conclusions: Cumulative incidence and risk for RGCs increased continuously in patients underwent GC gastrectomy. Close and lifelong endoscopy surveillance should be recommended for patients who received GC gastrectomy, especially those with high-risk factors. [ABSTRACT FROM AUTHOR]

Influenza infection is associated with cardiovascular complications that range significantly in presentation and severity. The cumulative incidence of cardiovascular complications due to laboratory‐confirmed influenza, however, is not reported in the literature. We conducted a systematic review and random‐effects meta‐analysis to evaluate the cumulative incidence and mortality rate of influenza virus‐related cardiovascular complications in hospitalized patients. We searched the PubMed and EMBASE databases for studies reporting acute myocardial infarction (AMI), heart failure (HF), arrhythmia of any kind, stroke or transient ischemic attack (TIA), and myocarditis in hospitalized patients with laboratory‐confirmed influenza virus infection. Prospective studies, retrospective cohort studies, and randomized controlled trials (RCTs) were included in the analysis. We followed the PRISMA checklist and used 95% confidence intervals (CIs) to report meta‐analysis outcomes. This study was registered on PROSPERO (CRD42023427849). After retrieving 2803 studies, we identified 19 studies (18 observational and 1 RCT) with relevant data, and we included 6936 patients in our analysis, of whom 690 (9.9%) developed a cardiovascular outcome of interest. The cumulative incidence of HF was 17.47% (95% CI: 5.06%–34.54%), arrhythmia of any kind 6.12% (95% CI: 0.00%–21.92%), myocarditis 2.56% (95% CI: 0.66%–5.38%), AMI 2.19% (95% CI: 1.03%–3.72%), and stroke or TIA 1.14% (95% CI: 0.00%–4.05%). The in‐hospital mortality rate from cardiovascular events was 1.38% (95% CI: 0.00%–4.80%). Cardiovascular complications occur in patients with influenza virus infection, with the cumulative incidence of specific cardiac manifestations varying considerably (1.51%–17.47%). Preventive strategies and close clinical monitoring after infection remain a priority. [ABSTRACT FROM AUTHOR]

Ethiopian farmers face a combination of risks in agricultural production during a single crop season. However, cumulative incidence assessment of the risks in the agriculture was not researched. Thus, this study aimed at assessing the cumulative incidence components in the production of the mung bean crop in the lowlands of South Ethiopia. A cross-sectional study was used with 384 mung bean farmers selected from lowlands of Gamo, Gofa and Wolaita zones. Thirteen original risk types were used to be categorized into a few factors through multiple factor analysis. Factor analysis identified latent variables with an Eigenvalues greater than one. The economic risk factor, the climate-related risk factor, and the systematic risk factor were the first three factors that explain 92.87 % of the inertia cumulatively. The rotated factor loading matrix indicated that under factor one, the encountered risks are an increase in the price of inputs, an increase in the price of food, and financial incidence, which accounted 50 % of the total variance. Under factor two extended dry spells, crop diseases, and wild animals’ damage and livestock diseases and deaths variables that accounted for 23.24 % of the total variance. The risk types categorized under systematic risks were social risks and political risks that accounted for 19.61 % of the total variance of risks encountered by mung bean farmers in the study area. Therefore, disentangling systematic risks is important by providing much-needed information to mung bean farmers and policymakers regarding systematic risk management priorities.

CD4 count recovery is the main goal for an HIV patient who initiated ART. Early ART initiation in HIV patients can help restore immune function more effectively, even when they have reached an advanced stage. Some patients may respond positively to ART and attain CD4 count recovery. Meanwhile, other patients failing to recover their CD4 count due to non-adherence, treatment resistance and virological failure might lead to HIV-related complications and death. The purpose of this study was to find the determinants of death in patients who failed to recover their CD4 count after initiating antiretroviral therapy. The data used in this study was obtained from KwaZulu-Natal, South Africa, where 2528 HIV-infected patients with a baseline CD4 count of 3 were initiated on ART. We used a Fine–Gray sub-distribution hazard and cumulative incidence function to estimate potential confounding factors of death, where CD4 count recovery was a competing event for failure due to death. Patients who had no tuberculosis were 1.33 times at risk of dying before attaining CD4 count recovery [aSHR 1.33; 95% CI (0.96–1.85)] compared to those who had tuberculosis. Rural patients had a higher risk of not recovering and leading to death [aSHR 1.97; 95% CI (1.57–2.47)] than those from urban areas. The patient’s tuberculosis status, viral load, regimen, baseline CD4 count, and location were significant contributors to death before CD4 count recovery. Intervention programs targeting HIV testing in rural areas for early ART initiation and promoting treatment adherence are recommended.

Objective: We aimed to determine the cumulative seizure occurrence, 1-year, and 5-years of preoperative seizures in gliomas, and an update on the predictors. Methods: This was a retrospective analysis of 239 patients with histopathologically confirmed gliomas in University Malaya Medical Centre, Malaysia, between 2008-2020. Kaplan-Meier curves were used to determine the cumulative incidence of seizures. Logistic regression was performed to determine the predictors of preoperative seizures. Results: A total of 80/239 patients (33.5%) had preoperative seizures. They were more commonly seen in those with younger age of presentation (40.0% in those <40 years old vs. 26.9% in =40 years old, p<0.05) and low-grade tumors (42.2% vs. 28.8% in high-grade tumors). Those with cortical involvement, especially the frontal lobe, or without focal deficit, headache, nausea, or vomiting were more likely to have seizures preoperatively. Logistic regression identified three significant predictors for preoperative seizure: absence of focal deficits at presentation (OR 6.090, 95% CI 3.110-11.925, p<0.001), cortical location (OR 3.834, 95% CI 1.363-10.786, p<0.05) and absence of headache at presentation (OR 2.487, 95% CI 1.139-5.431, p<0.05). The cumulative incidence of seizure was 29% at one year and 32% at 5-year for gliomas. Specifically, the seizure incidence was higher in low-grade gliomas (39% at 1-year) and certain tumor types such as ganglioglioma (50%), oligodendroglioma (48%), and astrocytoma (45%). Conclusion: The cumulative incidence of preoperative seizures in low-grade gliomas and certain tumor types is high. The predictors included cortical involvement and absence of focal neurological deficit or headache at presentation. [ABSTRACT FROM AUTHOR]

Background and purpose: Idiopathic Parkinson's disease (IPD) is a progressive neurodegenerative disorder that is strongly associated with age. The aim of the present study was to describe current sex‐ and age‐specific trends and regional differences in the incidence of IPD diagnosed in older people in Germany. Methods: This study was based on nationwide outpatient claims and drug prescription data from the German Statutory Health Insurance, covering approximately 87% of the general population. We conducted a cohort study in patients aged 50 years or older with observation time of at least 4 years. To assess the robustness of nationwide annual IPD incidence trends from 2013 to 2019, three case definitions with varying levels of stringency regarding coded outpatient diagnoses and drug prescriptions were applied. Results: In 2019, the population at risk comprised 30,575,726 persons. Using the primary and most specific case definition, annual age‐ and sex‐standardized cumulative IPD incidence decreased stepwise from 137 (2013) to 106 (2019) new cases per 100,000 persons. The decline in incidence was seen in both sexes, in all age groups and in the majority of German regions. The relative decrease (2013–2019) in the annual age‐ and sex‐standardized IPD incidence varied from 23% to 28% among case definitions. Conclusion: Our findings indicate a nationwide decline in the age‐ and sex‐standardized incidence of IPD from 2013 to 2019 in Germany. This trend was consistent using different case definitions. Further research is needed to elucidate the factors underlying this trend. [ABSTRACT FROM AUTHOR]

BackgroundLength of hospital stay (LOS) is one of the essential indicators for evaluating the efficiency and the quality-of-care service delivered. predicting LOS is critical for resource allocation, decision-making, lowering neonatal morbidity and death, enhancing clinical outcomes and parent counseling. In addition, extended hospital stays (long LOS_NICU) place a burden on the healthcare systems decreasing bed turnover rates as well as their financial stand and the mental stress on families. In Ethiopia, there is limited evidence on the determinant factors that influence on LOS.ObjectivesTo determine factors affecting neonatal intensive care unit length of stay for all preterm newborns who were discharged alive.MethodThe study used a secondary data source, was collected for the Study of Illness in Preterm (SIP) infants project. The research study was a multicenter, cross-sectional, observational clinical study that took place in five Ethiopia hospitals from July 1, 2016, to May 31, 2018. The predictors of LOS were determined using Fine-Gray's competing risk analysis.ResultsFor this study 3,511 preterm infants admitted to the NICU were analyzed. About 28.8% of the preterm infants died during their time in neonatal care while 66.6% were discharged alive. At the end of the study 4.6% babies were still in the NICU. The overall median LOS (death or discharge) was 7 days, with an interquartile range of 8 days. The cumulative incidence of discharge rose with increasing in gestational age and birth weight, on the contrary, the rate of discharge was decreased by 45.7% with the development of RDS (SDH ratio: 0.543), by 75.9% with the development of apnea (SDH ratio: 0.241), by 36.2% with sepsis, and by 43.6% with pneumonia (SDH ratio: 0.564).ConclusionsPreterm newborns with a low gestational age and birth weight have a greater probability of having a prolonged LOS. Complications of the medical conditions RDS, apnea, sepsis, pneumonia, anemia, asphyxia, and NEC substantially raise LOS considerably.

Summary: Background: The true incidence of SARS-CoV-2 infection in Costa Rica was likely much higher than officially reported, because infection is often associated with mild symptoms and testing was limited by official guidelines and socio-economic factors. Methods: Using serology to define natural infection, we developed a statistical model to estimate the true cumulative incidence of SARS-CoV-2 in Costa Rica early in the pandemic. We estimated seroprevalence from 2223 blood samples collected from November 2020 to October 2021 from 1976 population-based controls from the RESPIRA study. Samples were tested for antibodies against SARS-CoV-2 nucleocapsid and the receptor-binding-domain of the spike proteins. Using a generalized linear model, we estimated the ratio of true infections to officially reported cases. Applying these ratios to officially reported totals by age, sex, and geographic area, we estimated the true number of infections in the study area, where 70% of Costa Ricans reside. We adjusted the seroprevalence estimates for antibody decay over time, estimated from 1562 blood samples from 996 PCR-confirmed COVID-19 cases. Findings: The estimated total proportion infected (ETPI) was 4.0 times higher than the officially reported total proportion infected (OTPI). By December 16th, 2021, the ETPI was 47% [42–52] while the OTPI was 12%. In children and adolescents, the ETPI was 11.0 times higher than the OTPI. Interpretation: Our findings suggest that nearly half the population had been infected by the end of 2021. By the end of 2022, it is likely that a large majority of the population had been infected. Funding: This work was sponsored and funded by the National Institute of Allergy and Infectious Diseases through the National Cancer Institute, the Science, Innovation, Technology and Telecommunications Ministry of Costa Rica, and Costa Rican Biomedical Research Agency-Fundacion INCIENSA (grant N/A).

Competing risks data are commonly encountered in randomized clinical trials and observational studies. This paper considers the situation where the ending statuses of competing events have different clinical interpretations and/or are of simultaneous interest. In clinical trials, often more than one competing event has meaningful clinical interpretations even though the trial effects of different events could be different or even opposite to each other. In this paper, we develop estimation procedures and inferential properties for the joint use of multiple cumulative incidence functions (CIFs). Additionally, by incorporating longitudinal marker information, we develop estimation and inference procedures for weighted CIFs and related metrics. The proposed methods are applied to a COVID‐19 in‐patient treatment clinical trial, where the outcomes of COVID‐19 hospitalization are either death or discharge from the hospital, two competing events with completely different clinical implications. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the cumulative incidences of Non-melanoma skin cancer (NMSC)-specific mortality (NMSC-SM) and develop a competing risk nomogram for NMSC-SM. Methods: Data on patients diagnosed with NMSC between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. To identify the independent prognostic factors, univariate and multivariate competing risk models were used, and a competing risk model was constructed. Based on the model, we developed a competing risk nomogram to predict the 1-, 3-, 5-, and 8-year cumulative probabilities of NMSC-SM. The precision and ability to discriminate of the nomogram were evaluated through the utilization of metrics, such as receiver-operating characteristic (ROC) area under the curve (AUC), concordance index (C-index), and a calibration curve. Decision curve analysis (DCA) was employed to assess the clinical usefulness of the nomogram. Results: Race, age, the primary site of the tumor, tumor grade, size, histological type, summary stage, stage group, order of radiation and surgery, and bone metastases were identified as independent risk factors. The prediction nomogram was constructed using the variables mentioned above. The ROC curves implied the good discrimination ability of the predictive model. The nomogram's C-index was 0.840 and 0.843 in the training and validation sets, respectively, and the calibration plots were well fitted. In addition, the competing risk nomogram demonstrated good clinical usefulness. Conclusion: The competing risk nomogram displayed excellent discrimination and calibration for predicting NMSC-SM, which can be used in clinical contexts to help guide treatment decisions. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX)‐associated lymphoproliferative disorder (MTX‐LPD) is a troublesome problem in patients receiving MTX for rheumatoid arthritis (RA). However, its incidence, prognosis, and risk factors remain unclear. In this retrospective study, we evaluated the actual incidence, prognostic impact, and risk factors of MTX‐LPD. Of the 986 patients with RA treated with MTX, 90 patients experienced 95 new malignancies (NMs), with LPD as the most frequent in 26 patients. The cumulative LPD incidences were 1.3% and 4.7% at 5 and 10 years after MTX initiation, respectively. Among the 24 patients who discontinued MTX after developing LPD, 15 showed sustained regression, without difference in overall survival between patients with LPD and without NM. Inflammatory markers and absolute lymphocyte counts were not useful for early LPD development detection, but most of the patients with LPD had persistently elevated erythrocyte sedimentation ratios. Regarding concomitant drugs, tacrolimus increased the risk only if patients were not receiving biological disease‐modifying antirheumatic drugs (bDMARDs). bDMARDs did not increase the risk for any of the drugs or the number of classes used. The number of LPD cases was lower in patients with IL‐6A even after a long period after MTX, although with no statistically significant difference. Thus, approximately 1 in 20 patients with RA developed MTX‐LPD over the 10 years of MTX treatment, but it did not affect the survival of patients with RA. Tacrolimus increased the risk of developing LPD for certain patients and should be used with caution. [ABSTRACT FROM AUTHOR]

Jack-knife pseudo-observations have in recent decades gained popularity in regression analysis for various aspects of time-to-event data. A limitation of the jack-knife pseudo-observations is that their computation is time consuming, as the base estimate needs to be recalculated when leaving out each observation. We show that jack-knife pseudo-observations can be closely approximated using the idea of the infinitesimal jack-knife residuals. The infinitesimal jack-knife pseudo-observations are much faster to compute than jack-knife pseudo-observations. A key assumption of the unbiasedness of the jack-knife pseudo-observation approach is on the influence function of the base estimate. We reiterate why the condition on the influence function is needed for unbiased inference and show that the condition is not satisfied for the Kaplan–Meier base estimate in a left-truncated cohort. We present a modification of the infinitesimal jack-knife pseudo-observations that provide unbiased estimates in a left-truncated cohort. The computational speed and medium and large sample properties of the jack-knife pseudo-observations and infinitesimal jack-knife pseudo-observation are compared and we present an application of the modified infinitesimal jack-knife pseudo-observations in a left-truncated cohort of Danish patients with diabetes. [ABSTRACT FROM AUTHOR]

BackgroundsWhether there is a true increase in autism spectrum disorder (ASD) frequency or not remains unclear. Additionally, the rates of co-existing neurodevelopmental disorders (NDD) in a total population sample has not been fully examined before. Therefore, using a total population sample in Japan, we aimed to estimate the prevalence and cumulative incidence of autism spectrum disorder (ASD) annually, to determine whether there is a true increase in ASD prevalence by estimating the cumulative incidence of ASD annually, and to examine the rates of co-existing neurodevelopmental disorders (NDD).MethodIn this cross-sectional sequential design study, all 5-year-old children in the catchment area underwent the screening annually from the year 2013-2016. Screen-positive children were invited to participate in a comprehensive assessment, including child and parent interview, behavioral observation, and cognitive and motor function testing. All cases were reviewed by a multidisciplinary research team.ResultsCaregivers of 3954 children returned the screening, among which 559 children underwent the assessment with 87 children receiving an ASD diagnosis. Adjusted ASD prevalence was 3.22% (95% confidence interval (CI) 2.66-3.76%). The male to female ratio of the crude prevalence was 2.2:1. The cumulative incidence of ASD up to 5 years of age for the total study years was 1.31% (95% CI 1.00-1.62%). A generalized linear model revealed no significant linear trends in 5-year cumulative incidence over the study years. Only 11.5% of children had ASD alone; the remaining 88.5% were found to have at least one co-existing NDD.LimitationsModest sample size for a total population study.ConclusionsOur findings demonstrate the stability of the 5-year cumulative incidence of ASD, implying no true rise in ASD incident cases over the 4-year study period in the study catchment area. High rates of co-existing NDDs reflect the importance of investigating broad developmental challenges in children with ASD.

Background: Although endoscopic submucosal dissection (ESD) provides a high rate of curative resection, the remaining gastric mucosa after ESD is at risk for metachronous superficial gastric epithelial neoplasms (MSGENs). It leaves room for risk factors for developing MSGENs after ESD. This study aimed to identify clinicopathological risk factors for the occurrence of MSGENs, and to evaluate the association of Helicobacter pylori (H. pylori) with the MSGENs. Methods: We conducted a retrospective cohort study including 369 patients with 382 lesions that underwent ESD for adenoma/early gastric cancer. Results: Twenty-seven MSGENs occurred. The subjects were divided into MSGEN and not-MSGEN groups. There was a significantly higher frequency of histological intestinal metaplasia (HIM) and initial neoplasm location in the upper or middle parts (INUM) in the MSGEN group. The HIM and INUM groups had a significantly higher cumulative incidence of MSGENs. We compared 27 patients from the MSGEN group and 27 patients from the not-MSGEN group that were matched to the MSGEN group for variables including HIM and INUM. There was a significantly higher frequency of the spontaneous disappearance of H. pylori in the MSGEN group. Conclusions: HIM, INUM, and the spontaneous disappearance of H. pylori may be clinicopathological risk factors for developing MSGENs after ESD.

Background: This claims-based study aimed to assess recent nationwide trends in pediatric incidence of atopic diseases in Germany. Methods: Incidence of atopic dermatitis, asthma, and hay fever was assessed from 2013 to 2021 in annual cohorts of 0- to 17-year-old children and adolescents with statutory health insurance (N = 11,828,525 in 2021). Results: Incidence of atopic dermatitis remained largely unchanged (15.2 cases per 1000 children in 2021) while hay fever incidence exhibited a fluctuating trend over the study period and amounted to 8.8 cases per 1000 in 2021. Asthma incidence decreased gradually between 2013 (12.4/1000) and 2019 (8.9/1000). This downward trend was followed by a further disproportionate reduction from 2019 to 2020 (6.3/1000) and a re-increase in 2021 (7.2/1000). Conclusion: The findings complement nationwide prevalence surveys of atopic diseases in children and adolescents in Germany. Knowledge about temporal variations in risk of atopic diseases are crucial for future investigations of explanatory factors to enhance the development of preventive measures. While asthma incidence followed a declining trend throughout the study period, an unprecedentedly strong reduction in pediatric asthma risk was observed in 2020, the first year of the COVID-19-pandemic.

Competing risks data are commonly encountered in randomized clinical trials or observational studies. Ignoring competing risks in survival analysis leads to biased risk estimates and improper conclusions. Often, one of the competing events is of primary interest and the rest competing events are handled as nuisances. These approaches can be inadequate when multiple competing events have important clinical interpretations and thus of equal interest. For example, in COVID‐19 in‐patient treatment trials, the outcomes of COVID‐19 related hospitalization are either death or discharge from hospital, which have completely different clinical implications and are of equal interest, especially during the pandemic. In this paper we develop nonparametric estimation and simultaneous inferential methods for multiple cumulative incidence functions (CIFs) and corresponding restricted mean times. Based on Monte Carlo simulations and a data analysis of COVID‐19 in‐patient treatment clinical trial, we demonstrate that the proposed method provides global insights of the treatment effects across multiple endpoints. [ABSTRACT FROM AUTHOR]

Objective To investigate the occurrence and distribution of diabetic retinopathy （DR) in patients with diabetes in Jiading District, Shanghai. Methods DR examination was conducted in 13 communities of the jurisdiction for the patients with type 2 diabetes in 2017, and DR follow-up examination was regularly organized from 2018 to 2021, and new patients entered the follow-up cohort every year from 2018 to 2021. Finally, the 4-year cumulative incidence and incidence density of patients with retinopathy were calculated. DR examination included vision examination, computer optometry, fundus film, etc. Results A total of 13 184 diabetic patients participated in DR screening in 2017, and annual follow-up examinations were conducted from 2018 to 2021. A total of 8 758 patients were included in the cumulative incidence statistics. During the 4-year follow-up period，937 patients developed DR lesions, with acumulative incidence of 10.70% and an annual average incidence of 2.68%. The cumulative incidence of male （10.85%) was slightly higher than that of female （10.56%). The cumulative incidence decreased with the increase of age group without statistic difference. The patients enrolled in 2017 who participated in DR screening and did not detect DR lesions were followed up annually from 2018 to 2021, and the newly added patients were followed up from 2018 to 2021. The number of cases finally included in the incidence density statistics was 10 253. After 4 years of follow-up, the incidence density of DR in diabetic patients was 34.20/1 000 person-years. The incidence density was 35.54/1 000 person-years for males and 33.03/ 1000 person-years for females. Cox regression analysis showed that male （HR=1.278，95%CI：1.120- 1.458) diabetic patients were more likely to develop DR, and better naked eye vision （HR=0.373，95%CI： 0.172-0.809) was a protective factor for the development of DR in diabetic patients. Conclusion The incidence of DR in diabetic patients is relatively high in Jiading District, Shanghai. While the response rate of regular follow-up is relatively low. It is necessary to strengthen the publicity, carry out regular DR screening in diabetic patients, and focus on male, poor naked eye vision diabetic patients. [ABSTRACT FROM AUTHOR]

Patient and staff cohorting is part of a bundle approach in the response to multi-drug-resistant organisms, but its effectiveness is not fully clarified. This study compared the risks of acquiring vancomycin-resistant Enterococcus faecium (VREfm) at a hospital during a VREfm outbreak based on contact characteristics in order to better understand the effectiveness of cohorting. Exposure came from contact with patients with VREfm (infectors), including existing patients with VREfm and patients who acquired VREfm during the study period. Contact was defined as length of contact time, degree of sharing space, and care by the same nurses as those caring for infectors between January and March 2018. The outcome was VREfm acquisition as determined through monthly stool or rectal screening cultures. Incidence rates were calculated based on contact patterns, and incidence rate ratios (IRRs) were compared. Among 272 inpatients (4038 patient-days), 43 patients acquired VREfm with the same or similar pulsotype. Incidence rates were 8.45 per 1000 patient-days when susceptible inpatients were on the same ward as an infector but cared for by different nurses (reference), 16.96 when susceptible inpatients were on the same ward as an infector and cared for by the same nurses [IRR 2.01, 95% confidence interval (CI) 0.62–10.28], and 52.91 when susceptible inpatients shared a room with an infector (IRR 6.26, 95% CI 1.61–35.40). Compared with susceptible inpatients in a different room from infectors and not being cared for by the same nurses, the risk of VREfm acquisition could be six times higher for susceptible inpatients who are in the same room as infectors, and could be double for susceptible inpatients cared for by the same nurses as infectors. [ABSTRACT FROM AUTHOR]

Abstract Background Aggregation of lung cancer (LCa) in family members is well-documented. However, little is known on the familial risk of LCa when first-degree relatives (FDRs, parents or siblings) are diagnosed with LCa as a second primary malignancy (LCa-2). We aimed to investigate whether and to what extent a family history of LCa-2 was associated with an increased LCa risk. Methods In this Swedish national cohort we identified 127,865 individuals who had one FDR affected by LCa as a first primary cancer (LCa-1) and 15,490 individuals who had one FDR affected by LCa-2, respectively. We then estimated relative risk (RR) of LCa using those without cancer family history as reference. Results The number of LCa-2 has been increasing annually and rather similarly in men and women in the last decade. Familial RR of LCa was 1.96 (95%, 1.85–2.07) for LCa-1 family history and 1.89 for LCa-2 (1.62–2.21). Risk was especially high when FDR was diagnosed with early-onset LCa-2 and when siblings were affected by LCa-2. The RR was 1.53 (1.10–2.12) when LCa-2 in FDR was diagnosed within 26 months after first primary cancer, and it increased to 2.16 (1.62–2.90) when LCa-2 was diagnosed between 74 to 154 months. Higher risk was observed for first primary cancer of the ovary (4.45, 1.85–10.7), nervous system (3.49, 1.45–8.38), upper aerodigestive tract (2.83, 1.78–4.49) and cervix (2.55, 1.41–4.61), and for non-Hodgkin lymphoma (3.13, 1.57–6.27). Conclusions LCa risk is associated with diagnosis of LCa-2 in FDR to a similar degree as LCa-1 in FDRs.

Samuli Harju,1,2 Antti Saari,1,2 Reijo Sund,1 Ulla Sankilampi1,2 1Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland; 2Department of Paediatrics, Kuopio University Hospital, Kuopio, FinlandCorrespondence: Samuli Harju, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, PO Box 1627, Kuopio, 70211, Finland, Email samuli.harju@gmail.comBackground: Many primary and secondary disorders disturb growth and cause short stature (height below − 2 SDS) in childhood. Growth monitoring programs aim at their early detection but are not evidence-based: epidemiology of childhood growth disorders is poorly characterized, and no consensus exists on priority target conditions. Herein, we describe population-based epidemiological data on several primary and secondary growth disorders associated with short stature in childhood.Materials and Methods: This retrospective population-based 20-year birth cohort study examined 1 144 503 children (51% boys) born in Finland between 1998 and 2017, with 16.5 million care notifications including medical diagnoses. The first occurrences of key primary or secondary growth disorders were identified in multiple registers. Median ages at diagnosis (MAD), and age- and sex-specific cumulative incidences (CMI) from birth until 16 years of age were determined.Results: Turner syndrome was the most common primary growth disorder (CMI 52 per 100 000 at 16 years, MAD 4.0 years). Most primary growth disorders were diagnosed before the age of 4 years, and thereafter, secondary growth disorders increased in number. MAD of growth hormone deficiency (GHD) was 8.7 (boys) and 7.2 years (girls). At 16 years, the CMI of GHD was higher in boys than in girls (127 versus 93 per 100 000, respectively), whereas the CMI of hypothyroidism was higher in girls (569 versus 306 per 100 000). Celiac disease was the most common secondary growth disorder and more common in girls than in boys (988 versus 546 per 100 000 at 16 years, respectively).Conclusion: These population-based epidemiological data indicate that childhood growth monitoring should be age- and sex-specific. In the early childhood, the focus should be on primary growth disorders, and from preschool age also on secondary growth disorders. These results provide evidence for improving growth monitoring programs and diagnostic practices targeting on Turner syndrome, GHD, hypothyroidism, and celiac disease.Keywords: short stature, childhood, growth disorder, epidemiology, cumulative incidence

Background Immune protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be induced by natural infection or vaccination or both. Interaction between vaccine-induced immunity and naturally acquired immunity at the population level has been understudied. Methods We used regression models to evaluate whether the impact of coronavirus disease 2019 (COVID-19) vaccines differed across states with different levels of naturally acquired immunity from March 2021 to April 2022 in the United States. Analysis was conducted for 3 evaluation periods separately (Alpha, Delta, and Omicron waves). As a proxy for the proportion of the population with naturally acquired immunity, we used either the reported seroprevalence or the estimated proportion of the population ever infected in each state. Results COVID-19 mortality decreased as coverage of ≥1 dose increased among people ≥65 years of age, and this effect did not vary by seroprevalence or proportion of the total population ever infected. Seroprevalence and proportion ever infected were not associated with COVID-19 mortality, after controlling for vaccine coverage. These findings were consistent in all evaluation periods. Conclusions COVID-19 vaccination was associated with a sustained reduction in mortality at state level during the Alpha, Delta, and Omicron periods. The effect did not vary by naturally acquired immunity. [ABSTRACT FROM AUTHOR]

Objective: In Japan, cervical cancer screening consists of a cytology examination performed once every 2 years. We verified whether the risk of cervical intraepithelial neoplasia (CIN) 3 disease or higher (CIN3+) was equivalent to that of cytology negative cases (negative for intraepithelial lesion or malignancy [NILM]) for patients with a cytological diagnosis of "atypical squamous cells of undetermined significance (ASC-US)" who tested negative for human papillomavirus (HPV). Methods: Data from a total of 22,925 cases who had undergone cervical cancer screening at least twice or who had completed follow-up examinations after cervical screening at a single facility between April 2013 and April 2018 were analyzed. The cumulative incidence of CIN3+ was calculated for each category of initial cytology finding and HPV result (NILM, > ASC-US, ASC-US/HPV (unknown), ASC-US/HPV+, and ASC-US/HPV-). The statistical analysis was conducted using the Cox proportional hazards model. Results: The hazard ratio for the cumulative incidence of CIN3+ in 2 years relative to that for NILM cases was 2.7 (95% confidence interval=1.0-7.8) for > ASC-US cases, 0.5 (0.1-1.7) for ASC-US/HPV (unknown), 0.8 (0.3-2.4) for ASC-US/HPV+ cases, and 0.3 (0.1-1.0) for ASC-US/HPV- cases. Conclusion: Because the cumulative incidence of CIN3+ at 2 years for the ASC-US/HPV- cases was sufficiently low, compared with that of the NILM cases, we considered it reasonable and safe to perform HPV triage for ASC-US cases and to allow HPV-negative cases to return for their next screening in 2 years, which is the same follow-up schedule as that for NILM cases. [ABSTRACT FROM AUTHOR]

Background The coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact on global health, the magnitude of which appears to differ intercontinentally: For example, reports suggest that 271 900 per million people have been infected in Europe versus 8800 per million people in Africa. While Africa is the second-largest continent by population, its reported COVID-19 cases comprise <3% of global cases. Although social and environmental explanations have been proposed to clarify this discrepancy, systematic underascertainment of infections may be equally responsible. Methods We sought to quantify magnitudes of underascertainment in COVID-19's cumulative incidence in Africa. Using serosurveillance and postmortem surveillance, we constructed multiplicative factors estimating ratios of true infections to reported cases in Africa since March 2020. Results Multiplicative factors derived from serology data (subset of 12 nations) suggested a range of COVID-19 reporting rates, from 1 in 2 infections reported in Cape Verde (July 2020) to 1 in 3795 infections reported in Malawi (June 2020). A similar set of multiplicative factors for all nations derived from postmortem data points toward the same conclusion: Reported COVID-19 cases are unrepresentative of true infections, suggesting that a key reason for low case burden in many African nations is significant underdetection and underreporting. Conclusions While estimating the exact burden of COVID-19 is challenging, the multiplicative factors we present furnish incidence estimates reflecting likely-to-worst-case ranges of infection. Our results stress the need for expansive surveillance to allocate resources in areas experiencing discrepancies between reported cases, projected infections, and deaths. [ABSTRACT FROM AUTHOR]

Abstract Objectives To investigate if the risk of prostate cancer (PC) differs based on the order of primary PC diagnosed in first‐degree relatives (FDRs) given possibly different risk factors for PC as first primary cancer (PCa‐1) and second primary cancer (PCa‐2). Subjects and Methods In this Swedish nationwide cohort, PC diagnosis was followed for among 149,985 men with one FDR affected by PCa‐1, 10,972 with one FDR affected by PCa‐2 and 2,896,561 without any FDRs affected by cancer in a maximum of 57 years. PC patients were further followed for death due to PC since diagnosis. Relative risk (RR) of PC was estimated with Poisson regression and hazard ratio (HR) with Cox proportional hazard model. Results Compared to men without any FDRs affected by cancer, the RRs of PC in men with one FDR affected by PCa‐1 and PCa‐2 were 2.12 (95% confidence interval [CI]: 2.07–2.17) and 1.69 (1.54–1.85), respectively. The risk in men with one FDR affected by PCa‐2 was significantly lower than those with one FDR affected by PCa‐1 after additionally adjusting for family relationship (father‐son and brothers) and age at diagnosis of PC in FDR (RR PCa‐2 vs PCa‐1, 0.85, 95% CI, 0.78–0.94). PC patients with a family history of PCa‐2 were more likely to be detected at late‐stage and less likely to be diagnosed by screening, compared to those with a family history of PCa‐1. Patients whose PC was diagnosed after the diagnosis of PCa‐1 in FDRs had a better survival than those without a family history of cancer (HR, 0.88, 95% CI, 0.80–0.97), but no such association was observed among patients with a family history of PCa‐2. Conclusion Our study indicates a discrepancy between PC risks associated with a family history of PCa‐1 and PC‐2 and the reason behind it may be multifactorial.

Few studies focused on the incidence of brain metastasis in patients with acral and mucosal melanoma, and a better understanding of the incidences and predictors of brain metastasis is needed in these patients. A prospectively accrued cohort of 799 patients with acral and mucosal melanoma in stages I–III from July 2011 to December 2015 at Peking University Cancer Hospital were included in this study. Competing risk models (Fine and Gray) were used to estimate the cumulative incidence of brain metastasis and compare the differences in cumulative incidence curves between different primary lesions, stages, and molecular types. At a median follow-up time of 68.0 months, 60 of the 779 patients (7.7%) developed brain metastasis, and 261 (33.5%) patients developed extracranial metastasis. Considering the risk of competition, the cumulative incidence of brain metastasis at one year, two years, and five years after diagnosis were 5.1%, 10.2%, and 19.5%, respectively. Stage III, BRAF mutations, and NRAS mutations were associated with a high risk of brain metastasis in univariable analysis. Multivariate analysis showed BRAF mutations, and NRAS mutations had statistically correlated with an increased cumulative incidence of brain metastasis at diagnosis and all-time point of one year and two years after diagnosis. This study is the first to report the cumulative incidence and risk factors of brain metastasis for patients with acral and mucosal melanoma in stages I–III. Patients with BRAF and NRAS mutations had a higher incidence at diagnosis and all-time point, providing the basis for surveillance guidelines and further mechanic exploration. • Of 779 patients, 7.7% had brain metastasis with a median follow-up of 68.0 months. • Patients with BRAF and NRAS mutations an increased incidence of brain metastasis. • Patients with stage III and NRAS mutation had a high risk of extracranial metastasis. [ABSTRACT FROM AUTHOR]

Background: Aggregation of lung cancer (LCa) in family members is well-documented. However, little is known on the familial risk of LCa when first-degree relatives (FDRs, parents or siblings) are diagnosed with LCa as a second primary malignancy (LCa-2). We aimed to investigate whether and to what extent a family history of LCa-2 was associated with an increased LCa risk.Methods: In this Swedish national cohort we identified 127,865 individuals who had one FDR affected by LCa as a first primary cancer (LCa-1) and 15,490 individuals who had one FDR affected by LCa-2, respectively. We then estimated relative risk (RR) of LCa using those without cancer family history as reference.Results: The number of LCa-2 has been increasing annually and rather similarly in men and women in the last decade. Familial RR of LCa was 1.96 (95%, 1.85-2.07) for LCa-1 family history and 1.89 for LCa-2 (1.62-2.21). Risk was especially high when FDR was diagnosed with early-onset LCa-2 and when siblings were affected by LCa-2. The RR was 1.53 (1.10-2.12) when LCa-2 in FDR was diagnosed within 26 months after first primary cancer, and it increased to 2.16 (1.62-2.90) when LCa-2 was diagnosed between 74 to 154 months. Higher risk was observed for first primary cancer of the ovary (4.45, 1.85-10.7), nervous system (3.49, 1.45-8.38), upper aerodigestive tract (2.83, 1.78-4.49) and cervix (2.55, 1.41-4.61), and for non-Hodgkin lymphoma (3.13, 1.57-6.27).Conclusions: LCa risk is associated with diagnosis of LCa-2 in FDR to a similar degree as LCa-1 in FDRs. [ABSTRACT FROM AUTHOR]

Abstract Background Acquired aortic stenosis (AS) increases with age and has high mortality without intervention. Factors predicting its development are unclear, although atherosclerotic factors are assumed to be involved. Our aim in this study is to estimate the lifetime cumulative incidence and predictors of AS in middle-aged men. Methods We included a random sample of men (n = 9998) born 1915–1925 in Gothenburg, Sweden. From them, 7,494 were examined and followed until a diagnosis of AS or death (maximum follow-up time 42.8 years). We identified AS diagnosis from the Swedish National Patient Registry and deaths from the Swedish Cause of Death Registry by using International Classification of Disease (ICD) diagnostic criteria. To study time-dependent relationships between AS and risk factors with death as the competing risk, we divided the cohort into three overlapping follow-up groups: 25–43, 30–43 and 35–43 years. We used age-adjusted Cox proportional hazards model to identify predictors of AS. Results The lifelong cumulative incidence of AS was 3.2%. At baseline, participants in the third group had a healthier lifestyle, lower body mass index (BMI), blood pressure, and serum cholesterol levels. Higher BMI, obesity, cholesterol, hypertension, atrial fibrillation, smoking and heredity for stroke were associated with AS. With BMI of 20–22.5 as a reference, hazard ratios of being diagnosed with AS for men with a baseline BMI of 25–27.5 kg/m2, 27.5–30 kg/m2 and > 30 kg/m2 were 1.99 (95% CI 1.12–3.55), 2.98 (95% CI 1.65–5.40) and 3.55 (95% CI 1.84–6.87), respectively. Conclusions The lifetime cumulative incidence of AS in middle-aged male population was 3.2%. Multiple atherosclerotic risk factors, particularly high BMI might be associated with a higher risk of developing AS.

We compare two multi-state modelling frameworks that can be used to represent dates of events following hospital admission for people infected during an epidemic. The methods are applied to data from people admitted to hospital with COVID-19, to estimate the probability of admission to intensive care unit, the probability of death in hospital for patients before and after intensive care unit admission, the lengths of stay in hospital, and how all these vary with age and gender. One modelling framework is based on defining transition-specific hazard functions for competing risks. A less commonly used framework defines partially-latent subpopulations who will experience each subsequent event, and uses a mixture model to estimate the probability that an individual will experience each event, and the distribution of the time to the event given that it occurs. We compare the advantages and disadvantages of these two frameworks, in the context of the COVID-19 example. The issues include the interpretation of the model parameters, the computational efficiency of estimating the quantities of interest, implementation in software and assessing goodness of fit. In the example, we find that some groups appear to be at very low risk of some events, in particular intensive care unit admission, and these are best represented by using 'cure-rate' models to define transition-specific hazards. We provide general-purpose software to implement all the models we describe in the flexsurv R package, which allows arbitrarily flexible distributions to be used to represent the cause-specific hazards or times to events. [ABSTRACT FROM AUTHOR]

Background: Nucleos(t)ide analogues (NUCs) were proved to reduce hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients, but data were limited on their efficacy in cirrhotic CHB patients. Methods: A total of 447 cirrhotic CHB patients treated with tenofovir/entecavir were retrospectively analyzed and divided into HCC (n = 48) and non-HCC (n = 399) groups. The median follow-up period was 62.1 months. Results: A total of 48 patients (10.7%) developed HCC during surveillance. The annual incidence rate of HCC was 2.04 per 100 person-years. The cumulative incidence of HCC was 0.9%, 9.8%, and 22.1% at 1, 5, and 10 years, respectively. Significant predictors for HCC identified using a multiple Cox regression analysis were age ≥50 years (hazard ratio (HR): 2.34) and α-fetoprotein (AFP) ≥8 ng/mL (HR: 2.05). The incidence rate of HCC was 8.67-fold higher in patients with age ≥50 years and AFP ≥8 ng/mL (3.14 per 100 person-years) than those with age <50 years and AFP <8 ng/mL (0.36 per 100 person-years). Conclusions: Cirrhotic CHB patients with age <50 years and AFP <8 ng/mL had the lowest annual incidence of HCC. However, those with age ≥50 years or/and AFP ≥8 ng/mL had a significantly higher risk for HCC development and warrant a careful surveillance schedule. [ABSTRACT FROM AUTHOR]

Background: The average number of times a person will have surgery in their lifetime, and the amount of surgical healthcare resources they use, is unknown. Lifetime risk is a measure of the risk of an average person having a specific event within their lifetime. We report the lifetime risk of surgery and the change observed during the first year of the COVID-19 pandemic., Methods: We conducted a population cohort study using hospital episode statistics to identify all patients undergoing surgery between January 1, 2016, and December 31, 2020, in England. We calculated age- and sex-specific incidence rates of surgery and combined these with routinely available population and mortality data from the Office for National Statistics. We computed the probability of requiring surgery stratified by 5-yr epochs (age 0-4 to ≥90 yr). Our primary analysis calculated lifetime risk for all surgery using the life table method. We assessed the impact of the COVID-19 pandemic, comparing a pre-pandemic and a pandemic period., Results: Between 2016 and 2020, 23 427 531 patients underwent surgery, of which 11 937 062 were first surgeries. The average denominator population for England was 55.9 million. The lifetime risk of first surgery was 60.2% (95% confidence interval 55.1-65.4%) for women and 59.1% (95% confidence interval 54.2-64.1%) for men. The COVID-19 pandemic decreased the lifetime risk of first surgery by 32.3% for women and by 31.7% for men. This estimated lifetime risk should only be applied to the English population., Conclusions: This population epidemiological analysis suggests that approximately 60% of people in England will undergo surgery in their lifetime., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

CD4 count recovery is the main goal for an HIV patient who initiated ART. Early ART initiation in HIV patients can help restore immune function more effectively, even when they have reached an advanced stage. Some patients may respond positively to ART and attain CD4 count recovery. Meanwhile, other patients failing to recover their CD4 count due to non-adherence, treatment resistance and virological failure might lead to HIV-related complications and death. The purpose of this study was to find the determinants of death in patients who failed to recover their CD4 count after initiating antiretroviral therapy. The data used in this study was obtained from KwaZulu-Natal, South Africa, where 2528 HIV-infected patients with a baseline CD4 count of <200 cells/mm 3 were initiated on ART. We used a Fine-Gray sub-distribution hazard and cumulative incidence function to estimate potential confounding factors of death, where CD4 count recovery was a competing event for failure due to death. Patients who had no tuberculosis were 1.33 times at risk of dying before attaining CD4 count recovery [aSHR 1.33; 95% CI (0.96-1.85)] compared to those who had tuberculosis. Rural patients had a higher risk of not recovering and leading to death [aSHR 1.97; 95% CI (1.57-2.47)] than those from urban areas. The patient's tuberculosis status, viral load, regimen, baseline CD4 count, and location were significant contributors to death before CD4 count recovery. Intervention programs targeting HIV testing in rural areas for early ART initiation and promoting treatment adherence are recommended.

Background: The global COVID-19 pandemic has resulted in over seven million deaths, and IFI can further complicate the clinical course of COVID-19. Coinfection of COVID-19 and IFI (secondary IFI) pose significant threats not only to healthcare systems but also to patient lives. After the control measures for COVID-19 were lifted in China, we observed a substantial number of ICU patients developing COVID-19-associated IFI. This creates an urgent need for predictive assessment of COVID-19 patients in the ICU environment for early detection of suspected fungal infection cases., Methods: This study is a single-center, retrospective research endeavor. We conducted a case-control study on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients. The cases consisted of patients who developed any secondary IFI during their ICU stay at Jilin University China-Japan Union Hospital in Changchun, Jilin Province, China, from December 1st, 2022, to August 31st, 2023. The control group consisted of SARS-CoV-2 positive patients without secondary IFI. Descriptive and comparative analyses were performed, and a logistic regression prediction model for secondary IFI in COVID-19 patients was established. Additionally, we observed an increased incidence of COVID-19-associated pulmonary aspergillosis (CAPA) during this pandemic. Therefore, we conducted a univariate subgroup analysis on top of IFI, using non-CAPA patients as the control subgroup., Results: From multivariate analysis, the prediction model identified 6 factors that are significantly associated with IFI, including the use of broad-spectrum antibiotics for more than 2 weeks (aOR=4.14, 95% CI 2.03-8.67), fever (aOR=2.3, 95%CI 1.16-4.55), elevated log IL-6 levels (aOR=1.22, 95% CI 1.04-1.43) and prone position ventilation (aOR=2.38, 95%CI 1.15-4.97) as independent risk factors for COVID-19 secondary IFI. High BMI (BMI ≥ 28 kg/m 2 ) (aOR=0.85, 95% CI 0.75-0.94) and the use of COVID-19 immunoglobulin (aOR=0.45, 95% CI 0.2-0.97) were identified as independent protective factors against COVID-19 secondary IFI. The Receiver Operating Curve (ROC) area under the curve (AUC) of this model was 0.81, indicating good classification., Conclusion: We recommend paying special attention for the occurrence of secondary IFI in COVID-19 patients with low BMI (BMI < 28 kg/m 2 ), elevated log IL-6 levels and fever. Additionally, during the treatment of COVID-19 patients, we emphasize the importance of minimizing the duration of broad-spectrum antibiotic use and highlight the potential of immunoglobulin application in reducing the incidence of IFI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Su, Yu, Zhang, Huo and Zhao.)

Topic: To determine the cumulative incidence and features of glaucoma in Vogt-Koyanagi-Harada (VKH) syndrome patients compared to non-glaucoma patients., Clinical Relevance: Knowing the exact burden of secondary glaucoma in VKH could guide its screening and management in clinical practice as a part of the regular follow-up for VKH patients., Methods: The review protocol was pre-registered on PROSPERO [CRD42023462794]. PubMed, Scopus, Web of Science, EBSCOhost, and Google Scholar were searched for studies reporting the cumulative incidence and features of glaucoma presentation in VKH. A manual search was also conducted to supplement the primary search. Subgroup analyses based on glaucoma type, VKH stage, and patients' age were conducted. All analyses were conducted using STATA. Fixed- and random-effects models were selected according to the observed heterogeneity. Studies' methodological quality was determined using the NIH tool., Results: The analysis of 7084 eyes revealed a progressive increase in the cumulative incidence of secondary glaucoma over time. The cumulative incidence was lowest at VKH onset (7%) and highest at 15 years (26%). Open-angle (12%; 95%CI: 9-14%) is more common than angle-closure glaucoma (7%; 95%CI: 3-13%). Glaucoma cumulative incidence is highest in the chronic recurrent stage of VKH (33%; 95%CI: 12-59%) and among children <18 years of age (26%; 95%CI: 16-37%). Features associated with glaucoma occurrence in VKH showed comparable rates to non-glaucoma cases. However, a meta-analysis to determine risk factors of glaucoma development in VKH was not feasible secondary to the lack of adjusted risk measures in included studies. Studies' quality was questionable in 5 studies. The certainty of evidence was moderate-to-high., Conclusion: The cumulative incidence of glaucoma increases throughout VKH's course, with a higher tendency in children, chronic recurrent stages, and long-term follow-up. Future research should focus on examining risk factors of glaucoma development in VKH through adjusted multivariable regression models., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

OBJECTIVES After the third wave of coronavirus disease 2019 (COVID-19), by mid-February 2021, approximately 0.16% of the Korean population was confirmed positive, which appeared to be among the lowest rates worldwide at that time. However, asymptomatic transmission is challenging for COVID-19 surveillance. Therefore, a community-based serosurvey of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted to understand the effectiveness of Korea’s strong containment strategy. METHODS We collected 5,002 residual sera samples from January 30 to March 3, 2021, from 265 medical facilities in Seoul, 346 in Gyeonggi Province, and 57 in Incheon. Sixty samples from tertiary institutions were excluded. We defined the sub-regions according to the addresses of the medical facilities where the specimens were collected. Elecsys Anti-SARS-CoV-2 was used for screening, and positivity was confirmed using the SARS-CoV-2 sVNT Kit. Prevalence was estimated using sampling weights and the Wilson score interval for a binomial proportion with a 95% confidence interval. RESULTS Among the 4,942 specimens, 32 and 25 tested positive for COVID-19 in the screening and confirmatory tests, respectively. The overall crude prevalence of SARS-CoV-2 antibodies was 0.51%. The population-adjusted overall prevalence was 0.55% in women and 0.38% in men. The region-specific estimation was 0.67% and 0.30% in Gyeonggi Province and Seoul, respectively. No positive cases were detected in Incheon. CONCLUSIONS The proportion of undetected cases in Korea remained low as of early 2021. Therefore, an infection control strategy with exhaustive tracing and widespread pre-emptive testing appears to be effective in containing community spread of COVID-19.

BACKGROUND: Surgical wound complications are common and occur in between 3% and 12% of obese women after cesarean delivery. An understanding of the risk factors for wound complications may inform potential areas for clinical care improvement. OBJECTIVE: This study aimed to identify the incidence and predictors of surgical wound complications in obese women after cesarean delivery. STUDY DESIGN: This was a secondary analysis of the ADding negative pRESSure to improve healING, or DRESSING, randomized controlled trial conducted at 4 maternity hospitals in Australia. A total of 2035 women with a prepregnancy body mass index ≥30 kg/m2 undergoing cesarean delivery were included. Data were collected between October 2015 and December 2019 using self-reporting of signs and symptoms, the research nurses’ direct observation of the surgical site, and medical records. Independent blinded outcome assessors ascertained wound outcomes on the basis of self-reported data and medical records. Multivariable logistic regression models were used to identify independent risk factors for wound complications and surgical wound dehiscence. The 30-day cumulative incidence of wound complications and surgical wound dehiscence was calculated. RESULTS: Of the 2035 women, 317 (15.6%) developed a wound complication, whereas 211 (10.4%) developed surgical wound dehiscence. The predictors of a wound complication included 1 previous cesarean delivery (odds ratio, 1.41; 95% confidence interval, 1.05–1.90; P=.02) and ruptured membranes >12 hours (odds ratio, 1.69; 95% confidence interval, 1.08–2.66; P=.02). The odds of developing any wound complication decreased by 45% with vaginal cleansing (odds ratio, 0.55; 95% confidence interval, 0.42–0.72; P12 hours (odds ratio, 1.85; 95% confidence interval, 1.10–3.12; P=.02). The odds of developing surgical wound dehiscence decreased by 50% for vaginal cleansing (odds ratio, 0.50; 95% confidence interval, 0.36–0.69; P