Epidemiological Data Research Articles

Nested case control study of prevalence and aetiology of dementia in a rural Ugandan population, and a situational analysis of services available for affected families: a protocol. Part of the DEPEND Uganda study (Dementia EPidemiology, unmet Need and co-Developing Solutions)

Background The prevalence of dementia in low- and middle-income countries is increasing, yet epidemiological data from African populations remain scarce. Crucial risk factors differ in Africa from more intensively studied global areas, including a high burden of cerebrovascular disease and HIV, but lower rates of other risk factors like physical inactivity. Understanding dementia aetiology in African settings has been limited by the expensive and invasive nature of biomarker testing. This study leverages developments in blood-based and retinal imaging biomarker technology to examine the drivers of dementia in older Ugandans. People with dementia have complex needs benefiting from multi-dimensional support. Understanding current services will allow identification of barriers and opportunities to strengthen support available to people with dementia and their families. Methods The study is nested within the existing General Population Cohort run by the MRC/UVRI & LSHTM Research Unit. Currently, all adults aged 60+ (around 1400) are undergoing brief cognitive screening. In Part 1, cohort participants will be selected based on cognitive screening scores to undergo detailed cognitive assessment, using methods developed by the 10/66 Dementia Research Group. Part 2 is a case control study of people with and without dementia using antecedent data, questionnaires, physical assessment, retinal imaging, and Alzheimer’s blood-based biomarkers. We will also compare disability, frailty, quality of life, and social engagement in people with and without dementia. Part 3 assesses current provision of formal support for people with dementia through review of publicly available literature and expert interviews. Conclusions This is the first study in Africa using blood-based and retinal imaging biomarkers to examine the pathological processes underlying dementia, and it will systematically map services available for people with dementia. This paves the way for effective policy strategies for both dementia prevention and support for people with dementia and their families.

Genomic epidemiology of Clostridioides difficile Sequence Type 35 reveals intraspecies and interspecies clonal transmission

ABSTRACT Clostridioides difficile sequence type (ST) 35 has been found in humans and animals worldwide. However, its genomic epidemiology and clonal transmission have not been explored in detail. In this study, 176 C. difficile ST35 isolates from six countries were sequenced. Genomic diversity, clonal transmission and epidemiological data were analyzed. Sporulation and virulence capacities were measured. Four ribotypes (RT) were identified including RT046 (97.2%), RT656 (1.1%), RT427 (0.6%), and RT AI-78 (1.1%). Phylogenetic analysis of 176 ST35 genomes, along with 50 publicly available genomes, revealed two distinctive lineages without time-, region-, or source-dependent distribution. However, the distribution of antimicrobial resistance genes differed significantly between the two lineages. Nosocomial and communal transmission occurred in humans with the isolates differed by ≤ two core-genome single-nucleotide polymorphism (cgSNPs) and clonal circulation was found in pigs with the isolates differed by ≤ four cgSNPs. Notably, interspecies clonal transmission was identified among three patients with community acquired C. difficile infection and pigs with epidemiological links, differed by ≤ nine cgSNPs. Toxin B (TcdB) concentrations were significantly higher in human isolates compared to pig isolates, and ST35 isolates exhibited stronger sporulation capacities than other STs. Our study provided new genomic insights and epidemiological evidence of C. difficile ST35 intraspecies and interspecies clonal transmission, which can also be facilitated by its strong sporulation capacity.

A microbial symphony: a literature review of the factors that orchestrate the colonization dynamics of the human colonic microbiome during infancy and implications for future health

Since the advent of new sequencing and bioinformatic technologies, our understanding of the human microbiome has expanded rapidly over recent years. Numerous studies have indicated causal links between alterations to the microbiome and a range of pathological conditions. Furthermore, a large body of epidemiological data is starting to suggest that exposure, or lack thereof, to specific microbial species during the first five years of life has key implications for long-term health outcomes. These include chronic inflammatory and metabolic conditions such as diabetes, asthma, inflammatory bowel disease (IBD), and obesity, with the effects lasting into adulthood. Human microbial colonisation during these first five years of life is a highly dynamic process, with multiple environmental exposures recently being characterised to have influence before the microbiome stabilises and resembles that of an adult at 3-5 years. This short period of time, known as the window of opportunity, appears to “prime” immunoregulation for later life. Understanding and appreciating this aspect of human physiology is therefore crucial for clinicians, scientists, and public health officials. This review outlines the most recent evidence for the pre- and post-natal environments that order the development of the microbiome, how these influences metabolic and immunoregulatory pathways, and their associated health outcomes. It also discusses the limitations of the current knowledge base, and describes the potential microbiome-mediated interventions and public health measures that may have therapeutic potential in the future.

Rare diseases, trends and challenges for scientific advances: a snapshot of a decade of research in Brazil

Brazil is home to around 13 million rare disease patients, which represents a significant challenge for biomedical research and public health. This descriptive and exploratory study analyzed research protocols on rare diseases submitted to Plataforma Brasil between 2013 and 2023, with the aim of identifying trends, challenges and opportunities for scientific progress in this area. The research evaluated variables such as the number of studies submitted and approved, sample characteristics, type of study, experimental design, research phase, participation in international networks, and epidemiological data (ICD). The results indicate a substantial increase in the number of protocols submitted over the period analyzed, with an average approval rate of 87.26%. Most of the studies were conducted in public institutions, highlighting the fundamental role of the public sector in rare disease research in Brazil. These findings suggest a growing investment and interest in research in this area, which could boost the development of new therapies and interventions, as well as supporting the formulation of more effective public policies to meet the needs of patients with rare diseases.

Cardiac wasting in patients with cancer

AbstractPatients with cancer face a significant risk of cardiovascular death, regardless of time since cancer diagnosis. Elderly patients are particularly more susceptible as cancer-associated cardiac complications present in advanced stage cancer. These patients may often present with symptoms observed in chronic heart failure (HF). Cardiac wasting, commonly observed in these patients, is a multifaceted syndrome characterized by systemic metabolic alterations and inflammatory processes that specifically affect cardiac function and structure. Experimental and clinical studies have demonstrated that cancer-associated cardiac wasting is linked with cardiac atrophy and altered cardiac morphology, which impairs cardiac function, particularly pertaining to the left ventricle. Therefore, this review aims to present a summary of epidemiologic data and pathophysiological mechanisms of cardiac wasting due to cancer, and future directions in this field.

Extrahepatic Cancer Risk in Patients with Hepatitis C Virus Infection Treated with Direct-Acting Antivirals.

Chronic hepatitis C virus (HCV) infection is associated with an increased risk of extrahepatic cancers, particularly non-Hodgkin lymphoma. The introduction of direct-acting antivirals (DAAs) has revolutionized HCV therapy, resulting in high cure rates. However, concerns have been raised about potential effects on cancer risk. This review summarizes the current evidence on extrahepatic cancer risk in HCV-infected patients treated with DAAs. We examined epidemiologic data on HCV-associated extrahepatic cancers and explored potential mechanisms linking HCV to carcinogenesis outside the liver. Studies evaluating cancer outcomes after DAA therapy were critically reviewed while considering methodological challenges. While some studies suggested a reduced risk of extrahepatic cancers after DAA therapy, others showed no significant change. Limitations included short follow-up periods and confounding variables. Immunological changes following rapid HCV clearance may have complex effects on cancer risk. Long-term prospective studies and mechanistic investigations are needed to fully elucidate the relationship between DAA therapy and extrahepatic cancer risk in HCV patients. Clinicians should remain vigilant for extrahepatic malignancies in this population.

Abstract C156: Examining the role of T cell responses in colorectal cancer sex disparities

Abstract Purpose: Persistent sex disparities in colorectal cancer (CRC) incidence and mortality exist and vary by race and ethnicity. The overarching goal of this proposal is to quantify differences in the CRC tumor immune microenvironment by sex in the Latino Colorectal Cancer Consortium (LC3). Methods: The LC3 is a consortium of pooled individual-level data from Latino participants diagnosed with CRC from California, Florida, and Puerto Rico. Biospecimens, epidemiologic data, and clinical outcomes were collected from each contributing study. DNA was extracted from tumor tissue and paired germline or normal tissue samples. Whole exome sequencing was performed using established protocols. Global genetic ancestry was estimated from whole exome sequence data. High-throughput T cell receptor (TCR) sequencing was used to estimate features of the T cell receptor (TCR) repertoire (e.g. abundance, clonality), and tumor-infiltrating lymphocyte (TIL) counts were obtained through pathology review. We evaluated differences in TCR abundance and TILs by sex using linear models for continuous measurements and generalized linear models for binary or count measurements. Primary analyses were unadjusted, and secondary analyses adjusted for age at diagnosis, stage at diagnosis, tumor location (right colon vs. left colorectum), and microsatellite instability (MSI) status. To examine how genetic ancestry modified the relationship between sex and T cell responses, we fit separate models with an interaction term between each genetic ancestry proportion variable (i.e. African, European, Native American) and sex, and assessed effect modification using a likelihood ratio test. Results: To date, 240 participants had TCR repertoire profiling and whole exome sequencing data generated. 52% were male, with a mean age of 58. 17% of participants had rectal tumors. With respect to Hispanic ethnic heritage or country of origin, 49% of participants were of Mexican descent, followed by 13% of Central or South American descent, and 10% were of Puerto Rican descent. Mean T cell abundance was 0.18 (standard deviation (SD): 0.16) and mean clonality was 0.05 (SD: 0.05). Further analysis is underway. Conclusions: This project leverages within-Latino genetic diversity to disentangle the contributions of sex and genetic ancestry to variability in immune function and to understand how this may further sex disparities in CRC. We anticipate that results from this analysis will provide insight on the relationship between the tumor immune microenvironment and sex disparities in CRC. Citation Format: Nicole C. Loroña, Ya-Yu Tsai, Daniel Sobieski, Eric Cockman, Stephanie L. Schmit, Jane C. Figueiredo. Examining the role of T cell responses in colorectal cancer sex disparities [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C156.

Outbreak reconstruction with a slowly evolving multi-host pathogen: A comparative study of three existing methods on Mycobacterium bovis outbreaks

In a multi-host system, understanding host-species contribution to transmission is key to appropriately targeting control and preventive measures. Outbreak reconstruction methods aiming to identify who-infected-whom by combining epidemiological and genetic data could contribute to achieving this goal. However, the majority of these methods remain untested on realistic simulated multi-host data. Mycobacterium bovis is a slowly evolving multi-host pathogen and previous studies on outbreaks involving both cattle and wildlife have identified observation biases. Indeed, contrary to cattle, sampling wildlife is difficult. The aim of our study was to evaluate and compare the performances of three existing outbreak reconstruction methods (seqTrack, outbreaker2 and TransPhylo) on M. bovis multi-host data simulated with and without biases. Extending an existing transmission model, we simulated 30 bTB outbreaks involving cattle, badgers and wild boars and defined six sampling schemes mimicking observation biases. We estimated general and specific to multi-host systems epidemiological indicators. We tested four alternative transmission scenarios changing the mutation rate or the composition of the epidemiological system. The reconstruction of who-infected-whom was sensitive to the mutation rate and seqTrack reconstructed prolific super-spreaders. TransPhylo and outbreaker2 poorly estimated the contribution of each host-species and could not reconstruct the presence of a dead-end epidemiological host. However, the host-species of cattle (but not badger) index cases was correctly reconstructed by seqTrack and outbreaker2. These two specific indicators improved when considering an observation bias. We found an overall poor performance for the three methods on simulated biased and unbiased bTB data. This seemed partly attributable to the low evolutionary rate characteristic of M. bovis leading to insufficient genetic information, but also to the complexity of the simulated multi-host system. This study highlights the importance of an integrated approach and the need to develop new outbreak reconstruction methods adapted to complex epidemiological systems and tested on realistic multi-host data.

Abstract A075: Racial and ethnic inequities in receipt of degarelix among patients diagnosed with advanced prostate cancer in United States

Abstract Background: Prostate cancer (CaP) is the most commonly diagnosed non-cutaneous cancer among men in the United States (US). Limited data currently exists regarding inequities in access to androgen deprivation therapy (ADT) which is the backbone of systemic treatment in management of advanced CaP. Gonadotropin-releasing hormone (GnRH) antagonists, first approved in 2008, represent a novel class of ADT drugs with faster onset of action and without initial testosterone surge or symptom flare when compared to GnRH agonists. There is also some evidence that GnRH antagonists, compared to GnRH agonists, may be associated with lower cardiovascular complications. Thus, in this study, we assessed inequities in access to GnRH antagonist (degarelix) by examining the associations of race and ethnicity with initiation of this drug among patients diagnosed with distant CaP. Methods: Using the Surveillance, Epidemiology and End Results (SEER) data linked to Medicare fee-for-service (Parts A, B, and D), we identified a cohort of patients, at least 66 years of age, who were diagnosed with distant CaP between 2008 and 2019 with follow-up through 2020. We defined treatment initiation with a GnRH antagonist (degarelix) or GnRH agonists (leuprolide, goserelin, histrelin, or triptorelin) as starting treatment with the study drug within one year after diagnosis. Poisson regression models were used to estimate adjusted rate ratios (aRR) and 95% confidence intervals (CI) for the association between race and ethnicity and degarelix treatment initiation (vs GnRH agonists, no treatment). All models were adjusted for age and Gleason score and compared Non-Hispanic Black (NHB), Hispanic, Non-Hispanic Asian American and Pacific Islander (NHAAPI), and Non-Hispanic American Indian and Alaska Native (NHAIAN) with Non-Hispanic White (NHW) patients. Results: There were 25,277 patients diagnosed with CaP in our analytic cohort, 3,033 (12.0%) initiated degarelix, and 14,045 (55.6%) initiated GnRH agonists over the study period. Mean (SD) age in the study population was 77.8 (7.8). Among all patients, 19,231 (76.1%) were NHW, 3,013 (11.9%) were NHB, 2,075 (8.2%) were Hispanic, 770 (3.0%) were NHAAPI, and 119 (0.5%) were NHAIAN. In the primary analysis, NHB (aRR: 0.58, 95% CI: 0.51-0.66), Hispanic (aRR: 0.59, 95% CI: 0.51-0.69), NHAIAN (aRR: 0.85, 95% CI: 0.49-1.47), and NHAAPI (aRR: 0.75, 95% CI: 0.59-0.94) were less likely to initiate degarelix compared with NHW patients. Discussion: In this US population-based study of patients diagnosed with distant CaP, we observed lower rates of treatment initiation with degarelix among patients of all other racial and ethnic groups compared to NHW patients, which may suggest lower access to these new class of ADT in these groups. Additional research is needed to elucidate health systems, provider, and patient access barriers that contribute to these inequities. Citation Format: Farzin Khosrow-Khavar, Mingchao He, Elizabeth Handorf, Tina Mayer, Thomas Jang, Saum Ghodoussipour, David Golombos, Biren Saraiya, Elisa V. Bandera, Hari S. Iyer. Racial and ethnic inequities in receipt of degarelix among patients diagnosed with advanced prostate cancer in United States [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A075.

Abstract A004: Validation of the PREDICT breast version 3.0 prognostic tool in the US breast cancer patients

Abstract PREDICT Breast v3 is the latest version of a prognostic tool designed to predict the treatment responses for early invasive breast cancer patients. It was developed using data from approximately 35,000 women diagnosed between 2000 and 2018 in the United Kingdom. However, its performance in the United States (US) population is unknown. This study aims to validate PREDICT Breast v3 using the newly released Surveillance, Epidemiology, and End Results (SEER) outcome data for US breast cancer patients and to address potential health disparities. We selected over 860,000 female patients diagnosed with primary breast cancer between 2000 and 2021 and followed for at least 5 years from the SEER database. The model’s performance was measured by calibration and discrimination; comparing predicted and observed 5-, 10- and 15-year breast cancer-specific survival outcomes and determining discrimination through the area under the receiver-operator curves (AUC). PREDICT Breast v3 demonstrated good calibration and discrimination for both short- and long-term up breast cancer-specific mortality in US populations. The predicted 10-year breast cancer-specific mortality differed from observed by 11% in ER-positive and 6 % in ER-negative patients. The AUCs for 15-year breast cancer-specific mortality were 0.81 for ER-positive patients and 0.76 for ER-negative patients. When stratified by race and ethnicity, the model showed strong performance in Non-Hispanic Asians ER-positive patients, despite being originally developed based on the UK population. These results are consistent with previous validations in Malaysia, Japan, and other Asian countries for PREDICT Breast v2. However, the model poorly estimated the number of deaths in Non-Hispanic Black individuals for both ER-positive and ER-negative. In conclusion, this study marks the first validation of PREDICT Breast v3 in the US and demonstrates that it is a reliable and generalizable tool, capable of providing longer term follow-up time up to 15 years for a wide and diverse population. Citation Format: Yi-Wen Hsiao, Paul Pharaoh, Pei-Chen Peng. Validation of the PREDICT breast version 3.0 prognostic tool in the US breast cancer patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A004.

Abstract B159: Could cultural adaptation of nutrition education improve survivorship outcomes among African American/black women with reproductive cancers?

Abstract Background/Significance: Cancer epidemiological data suggest African American/Black women experience the lowest relative survival rate for reproductive cancers compared to other racial/ethnic groups, despite these cancers being most prevalent among White women. Findings from recent studies suggest contributors to these adverse outcomes include socio-cultural and lifestyle factors, including diet, physical activity, and smoking. As an intervention strategy, it has been recommended dietary changes may enhance overall health and survival among AA/B women with reproductive cancers. However, inequalities in access to nutritious foods and culturally and linguistically appropriate nutrition information may serve as an impediment to making healthy food choices. Methods: An environmental scan was conducted by reviewing peer reviewed literature and online nutrition information sources to identify available, easily accessible, culturally adapted nutrition education for AA/B reproductive cancer survivors. Focus groups with breast and endometrial cancer survivors will ensure to inform the development of culturally targeted nutritional programs for cancer survivors. Results: Our literature review reveals a growing body of evidence indicating the potential benefits of culturally adapted dietary modifications post-diagnosis for African American/Black women with reproductive cancers, suggesting improved outcomes. Notably, the review underscores the critical role of culturally relevant nutrition information, disseminated by culturally affiliated individuals, with technology playing a pivotal role in accessibility facilitation. This research study aims to clarify the barriers and facilitators encountered by African American/Black women in accessing culturally and linguistically appropriate information, thereby enhancing understanding of factors influencing cancer survivorship outcomes. Conclusion and Implications/Discussion: Seeking to improve the survivorship of reproductive cancers in AA/B women through enhanced dietary patterns, this study merges insights from a systematic literature review and an environmental scan. Offering a comprehensive understanding of available nutritional information for AA/B women. Recognizing both strengths and gaps in existing resources, our research serves as a foundation for developing or adapting culturally specific nutritional programs to improve survivorship outcomes for reproductive cancers. Anticipating that our findings will contribute to understanding barriers and facilitators in accessing culturally and linguistically appropriate information, we aim to enhance cancer survivorship outcomes for AA/B women. Acknowledgement of Funding: The project described was supported by Award Number CHERC-MSI-21-166-01-CHERC-MSI. from the American Cancer Society (ACS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the ACS. Citation Format: Desiree Rivers, Zakirah L Abdul-Hameed. Could cultural adaptation of nutrition education improve survivorship outcomes among African American/black women with reproductive cancers? [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B159.

Prevalence, causes and factors associated with vision impairment in Limpopo province

Background: Epidemiological data on the prevalence, causes and risk factors associated with vision impairment (VI) is necessary to evaluate the effectiveness of eye care services.Aim: To determine the prevalence, causes and factors associated with VI among patients presenting to public hospitals of Limpopo province, South Africa.Setting: This study was conducted in public hospitals.Methods: A retrospective chart review of patients seen from April 2019 to March 2022 in 29 public hospitals was conducted. The following information was extracted: demographic information, medical history, visual acuity (VA), refractive and ophthalmoscopy findings.Results: Of the 1140 participants, 56.1% were women. Participants’ ages ranged from 5 to 94 years. The prevalence of VI was 61.5%. Most had moderate-severe VI (57.3%), followed by blindness (22.7%) and mild VI (20.0%). The leading causes of VI were uncorrected refractive error (URE) (28.1%), cataract (26.0%) and glaucoma (25.0%). The main causes of blindness were glaucoma (42.8%) and cataract (32.1%); while URE (7.5%), retinal anomalies (7.5%) and corneal anomalies (6.9%) accounted for almost equal proportions of blindness. Participants aged 50–64 years (odds ratio [OR]: 1.7; 95% confidence interval [CI]: 1.2–2.6); 65 years and older (OR: 6.6; 95% CI: 4.3–10.2); and those diagnosed with systemic hypertension (OR: 2.5; 95% CI: 1.9–3.2) and diabetes mellitus (OR: 2.9; 95% CI: 1.9–4.4) had increased risk of VI.Conclusion: The prevalence of VI in this population is relatively high. The main causes of VI are correctable, suggesting the need for improved measures to prevent avoidable VI.Contribution: The study addresses the gap in the province’s current prevalence, causes and factors related to VI.

New staging criteria predicting m-tor inhibitors treatment effect of renal angiomyolipoma in tuberous sclerosis complex patients.

We aimed to launched new staging criteria to predict mTOR inhibitors treatment effect of renal angiomyolipomas (r-AMLs) in TSC patients. 40 TSC patients with 69 r-AMLs were divided into two groups based on the efficacy of 6-month mTOR inhibitor treatment. Epidemiological data, therapeutic response, and predictive factors of enrolled patients were collected and analyzed. Age, sex, maximum diameter, maximum cross-sectional area (CSAmax), unenhanced mean CT value, enhanced mean CT value, and added value of enhanced CT of largest r-AML at baseline were assessed as potential influencing factors. Receiver operating characteristic (ROC) curve analysis and the area under the ROC curve (AUC) was used to estimate prediction power. After 6 months of mTOR inhibitor treatment, the tumor reduction rates in the two groups were 55.87% and 16.44% (P < 0.001). At the start of treatment, the maximum diameters, CSAmax, added value of enhanced CT of the target lesion in two groups were 7.70 ± 0.73cm vs. 13.18 ± 1.23cm(P = 0.028), 57.40 ± 10.76cm2 vs. 167.29 ± 33.09cm2 (P = 0.015), and 62.32 ± 5.03HU vs. 33.06 ± 3.13HU (P = 0.009), respectively. AUCs of CSAmax, added value of enhanced CT, and combination of both were 0.8024, 0.7672, and 0.8116, respectively (P < 0.001). Cut-off values of CSAmax combined with the added value of enhanced CT were 40cm2 and 46HU. AUCs of maximum diameters, combination of maximum diameters and added value of enhanced CT were 0.7600 and 0.8100, respectively (P < 0.001), with cut-off values of 6.6cm and 46 HU. New staging criteria, based on CSAmax and added value of enhanced CT, can predict the treatment efficiency of m-TOR inhibitors for r-AMLs in TSC patients. A simplified version based on maximum diameter and added value of enhanced CT of lesion has also been proposed.

Effect of Chemotherapy and Surgery Timing on Mortality in Upper and Lower Extremity Osteosarcoma

Abstract Background Surgery with both neoadjuvant and adjuvant chemotherapy represents the standard of care for extremity osteosarcoma despite a lack of high-quality evidence for its use, and trial evidence that suggests that up-front surgery may result in better outcomes. This study estimated the difference in overall survival for the standard of care (“Neoadjuvant First”) vs upfront surgery first followed by adjuvant chemotherapy (“Surgery First”). Patients and methods Using Surveillance, Epidemiology, and End Results data, we identified patients age 5-29, diagnosed with a primary cancer of upper or lower extremity osteosarcoma between 2007 and 2019 who received surgery and chemotherapy. Our primary endpoint was the 5-year survival difference between the Surgery First and Neoadjuvant First groups. Results Adjusted 5-year survival was 74% for Surgery First patients and 67% for Neoadjuvant First patients, with a survival difference of 6.9% (95% CI -4.2% - 16.1%). In sensitivity analyses of 5-year survival, the results were consistent, showing a 6.8% to 13.7% higher 5-year survival in Surgery First patients. Significant mortality risk factors included older age, larger tumor size, the type of resection (salvage vs amputation), and stage 3-4 disease (vs stage 1-2 disease). Conclusion The evidence supporting neoadjuvant therapy in osteosarcoma care is weak. However, there is evidence that pausing chemotherapy in the peri-surgical period might affect outcomes. Consequently, this study, and its consistency with the results from the only randomized trial, suggests that there is reason to revisit a prospective, randomized trial of osteosarcoma treatment regarding the timing of surgery and chemotherapy.

Comparison of characteristics of children hospitalized for respiratory syncytial virus infection during the pre- and post-COVID-19 eras: a multicenter retrospective study

BackgroundRespiratory syncytial virus (RSV), a leading cause of lower respiratory tract infection (LRTI) among children, has resurged in the form of endemic or even pandemic in many countries and areas after the easing of COVID-19 containment measures. This study aimed to investigate the differences in epidemiological and clinical characteristics of children hospitalized for RSV infection during pre- and post-COVID-19 eras in Yunnan, China.MethodsA total of 2553 pediatric RSV inpatients from eight hospitals in Yunnan were retrospectively enrolled in this study, including 1451 patients admitted in 2018–2019 (pre-COVID-19 group) and 1102 patients admitted in 2023 (post-COVID-19 group). According to the presence or absence of severe LRTI (SLRTI), patients in the pre- and post-COVID-19 groups were further divided into the respective severe or non-severe subgroups, thus analyzing the risk factors for RSV-associated SLRTI in the two eras. Demographic, epidemiological, clinical, and laboratory data of the patients were collected for the final analysis.ResultsA shift in the seasonal pattern of RSV activity was observed between the pre-and post-COVID-19 groups. The peak period of RSV hospitalizations in the pre-COVID-19 group was during January–April and October–December in both 2018 and 2019, whereas that in the post-COVID-19 group was from April to September in 2023. Older age, more frequent clinical manifestations (fever, acute otitis media, seizures), and elevated laboratory indicators [neutrophil-to-lymphocyte ratio (NLR), c-reactive protein (CRP), interleukin 6 (IL-6), co-infection rate] were identified in the post-COVID-19 group than those in the pre-COVID-19 group (all P < 0.05). Furthermore, compared to the pre-COVID-19 group, the post-COVID-19 group displayed higher rates of SLRTI and mechanical ventilation, with a longer length of hospital stay (all P < 0.05). Age, low birthweight, preterm birth, personal history of atopy, underlying condition, NLR, IL-6 were the shared independent risk factors for RSV-related SLRTI in both pre- and post-COVID-19 groups, whereas seizures and co-infection were independently associated with SLRTI only in the post-COVID-19 group.ConclusionsAn off-season RSV endemic was observed in Yunnan during the post-COVID-19 era, with changed clinical features and increased severity. Age, low birthweight, preterm birth, personal history of atopy, underlying condition, NLR, IL-6, seizures, and co-infection were the risk factors for RSV-related SLRTI in the post-COVID-19 era.

From conceptualising to modelling structural determinants and interventions in HIV transmission dynamics models: a scoping review and methodological framework for evidence-based analyses

Abstract Background Including structural determinants (e.g. criminalisation, stigma, inequitable gender norms) in dynamic HIV transmission models is important to help quantify their population-level impacts and guide implementation of effective interventions that reduce the burden of HIV and inequalities thereof. However, evidence-based modelling of structural determinants is challenging partly due to a limited understanding of their causal pathways and few empirical estimates of their effects on HIV acquisition and transmission. Methods We conducted a scoping review of dynamic HIV transmission modelling studies that evaluated the impacts of structural determinants, published up to August 28, 2023, using Ovid Embase and Medline online databases. We appraised studies on how models represented exposure to structural determinants and causal pathways. Building on this, we developed a new methodological framework and recommendations to support the incorporation of structural determinants in transmission dynamics models and their analyses. We discuss the data and analyses that could strengthen the evidence used to inform these models. Results We identified 17 HIV modelling studies that represented structural determinants and/or interventions, including incarceration of people who inject drugs (number of studies [n] = 5), violence against women (n = 3), HIV stigma (n = 1), and housing instability (n = 1), among others (n = 7). Most studies (n = 10) modelled exposures dynamically. Almost half (8/17 studies) represented multiple exposure histories (e.g. current, recent, non-recent exposure). Structural determinants were often assumed to influence HIV indirectly by influencing mediators such as contact patterns, condom use, and antiretroviral therapy use. However, causal pathways’ assumptions were sometimes simple, with few mediators explicitly represented in the model, and largely based on cross-sectional associations. Although most studies calibrated models using HIV epidemiological data, less than half (7/17) also fitted or cross-validated to data on the prevalence, frequency, or effects of exposure to structural determinants. Conclusions Mathematical models can play a crucial role in elucidating the population-level impacts of structural determinants and interventions on HIV. We recommend the next generation of models reflect exposure to structural determinants dynamically and mechanistically, and reproduce the key causal pathways, based on longitudinal evidence of links between structural determinants, mediators, and HIV. This would improve the validity and usefulness of predictions of the impacts of structural determinants and interventions.

Epidemiology, microbiology and antibiotic treatment of bacterial and fungal meningitis among very preterm infants in China: a cross-sectional study

ObjectiveNeonatal meningitis significantly contributes to neonatal morbidity and mortality, yet large-scale epidemiological data in developing countries, particularly among very preterm infants (VPIs), remain sparse. This study aimed to describe the...

Neisseria gonorrhoeae treatment failure to the recommended antibiotic regimen-Québec, Canada, 2015-19.

To describe Neisseria gonorrhoeae treatment failure to the recommended antimicrobial regimens (azithromycin, cefixime and ceftriaxone). Our study was a longitudinal analysis of treatment failures from an observational open cohort of gonococcal infection cases collected in Québec, Canada (n = 2547) between September 2015 and December 2019. Epidemiological and clinical data were collected using a self-administered questionnaire, direct case interviews and chart reviews. Antimicrobial susceptibility testing was performed using the agar dilution method. To be retained as a treatment failure, cases must have had (i) a laboratory-confirmed gonococcal infection; (ii) a documented treatment; (iii) a positive test of cure (TOC) performed within a defined period and (iv) no sexual contact (vaginal, oral or anal), even protected with a condom, between the beginning of treatment and the positive TOC. A broader definition, including suspected cases, was also examined. Among 1593 cases where a TOC was performed, 83 had a positive TOC: 11 were retained as treatment failure, and 6 were considered suspected cases (overall = 17/1593; 1.1%). Possible explanations for retained or suspected treatment failure included resistance to the antibiotics used for treatment (n = 1), pharyngeal infection (n = 9, of which 5 had been treated with ceftriaxone and 4 with other regimens); and azithromycin monotherapy (n = 1). Some cases had more than one potential explanation. Treatment failure occurred in 1.1% of cases of Neisseria gonorrhoeae infection for which a TOC was performed, including some cases of pharyngeal infection treated with ceftriaxone.

The risk factors and predictors of injury among collegiate rugby players under the age of 20.

The risk of injury in rugby is high, due to the contact nature of the game. Players are constantly exposed to impact and collision during training and match-play. Rugby union consists of various risk factors that predispose players to injury. The aim of the study was to determine the risk factors of injury and to predict the risk of injury per playing position during match-play. The study followed a quantitative, non-experimental, and cross-sectional research design. A total of 252 male rugby players, aged 18 to 20 years, who played in a collegiate rugby competition in South Africa (SA) for the 2022 season were conveniently sampled for the study. The playing position, time of injury (whether during a match or training), use of protective equipment, and phase of play in which the injury occurred were recorded. Injury data was captured by qualified healthcare professionals using an adapted injury surveillance questionnaire. The study found that potential risk factors for injury included illegal or dangerous play, playing in the second half of the match (more specifically the third quarter of the match), and playing in the offensive part of the field (more specifically between the opposition-22 and halfway line). Contact events were the most common cause of match injury (91.1%). The half of the match in which an injury was sustained was significantly different between forwards and backs (P=0.011). A statistically significant association was found between playing position and the phase of play in which injury was sustained (P=0.021). Regression analysis showed that playing between the opposition-22 m line and the halfway line was a significant predictor of injury for both forwards and backs (P=0.035). In conclusion, potential risk factors for injury were related to dangerous play, time during the match (specifically the third quarter of the match), and location of play (specifically between the opposition-22 m line and halfway line). The area of play was a significant predictor of injury for all players. It is recommended that greater efforts in collecting epidemiological data need to be made to broaden the knowledge base on injuries and provide strategies to coaches and players to reduce the risk of injury in rugby.

Mortality associated with osteoporosis and pathological fractures in the United States (1999–2020): a multiple-cause-of-death study

BackgroundOsteoporosis with pathological fractures is a significant public health issue, contributing to morbidity, disability, diminished quality of life, and increased mortality. Understanding mortality trends related to this condition is crucial for developing effective interventions to reduce mortality and improve healthcare outcomes. This study aimed to analyze trends and causes of death associated with osteoporosis and pathological fractures in the United States using a multi-cause approach.MethodsAnnual death and age-standardized mortality rate (ASMR) data from 1999 to 2020 were obtained from the Centers for Disease Control and Prevention (CDC) mortality database. Death certificates listing ICD-10 M82 (osteoporosis with pathological fracture) as an underlying or related cause of death were analyzed. Epidemiological data were analyzed, and the ASMR data were calculated for each year, and trends were assessed using the Cochran-Armitage trend test.ResultsFrom 1999 to 2020, there were 40,441 deaths related to osteoporosis with pathological fractures in the United States, with a female-to-male ratio of 5.6:1. Among these, 12,820 deaths (31.7%) listed osteoporosis with pathological fractures as the underlying cause of death (UCD), yielding a female-to-male ASMR ratio of approximately 5.0-7.7:1. When classified as a non-UCD, the ASMR ratio was approximately 4.8–6.2:1. At the same time, we found that the total number of deaths classified as UCD and multiple causes of death (MCD), but the trend ratio of the two groups in different years did not change statistically significant (P > 0.05), and the ASMR of both groups showed a downward trend. The UCD-to-MCD ratio increased between 1999 and 2007, then decreased from 2007 to 2020. As MCD, the number of female deaths was more than that of male, and both showed a decreasing trend, but there was no statistical significance in the change of trend ratio in different years (P > 0.05). Deaths were predominantly concentrated in individuals over 75 years of age, with those over 84 years being the most affected. The number of deaths in different age groups showed a decreasing trend, and the change of trend ratio in different years was statistically significant (P < 0.05). White individuals had the highest number of deaths. The leading causes of death were heart diseases, chronic lower respiratory diseases, and alzheimer’s disease. In addition, the number of deaths of patients with prostate cancer and breast cancer showed a significant downward trend, and the change of trend ratio between the two groups in different years was statistically significant (P < 0.05).ConclusionsAlthough mortality from osteoporosis with pathological fractures is decreasing, anti-osteoporosis therapy remains essential for elderly patients. Healthcare providers should remain vigilant for potential complications, including malignant neoplasms, and ensure timely diagnosis and treatment to further reduce mortality in this population.