Patterns of venous thromboembolism risk, treatment, and outcomes among patients with cancer from uninsured and vulnerable populations.

The epidemiology of cancer-associated thrombosis (CAT) among uninsured and vulnerable populations in the US is not well-characterized. We performed a retrospective cohort study for patients with newly diagnosed cancer from 2011 to 2020 at Harris Health System, which cares for uninsured residents in the Houston metropolitan area. Patient demographics, NCI comorbidity index, area of deprivation index (ADI), cancer histology, staging, and systemic therapy data were extracted. CAT included overall venous thromboembolism (VTE) or pulmonary embolism +/- lower extremity deep vein thrombosis (PE/LE-DVT) within 1 year of diagnosis. We used multivariable Fine-Gray models to assess the associations with CAT accounting for death as a competing risk. Among 15 342 patients, 74% were uninsured and 84% lived in socioeconomically disadvantaged neighborhoods. There were 16% Non-Hispanic White (NHW), 28% Non-Hispanic Black (NHB), 50% Hispanic (27% Mexican), and 6% Asian/Pacific Islanders (API). The 1-year CAT incidence rate was 14.6%. Overall VTE was lower for Hispanics versus NHW (SHR 0.87 [0.76-0.99]) and API versus NHW (SHR 0.58 [0.44-0.77]). PE/LE-DVT was higher for NHB versus NHW (SHR 1.18 [1.01-1.39]). CAT was also associated with chemotherapy-based regimens (+/- immunotherapy), age, obesity, cancer type/staging, VTE history, and recent hospitalization. NCI comorbidity and ADI scores were associated with mortality but not CAT. In a large cohort of underserved patients with cancer, we identified an elevated incidence of CAT with known and novel risk predictors. Hispanics had lower adjusted rates of CAT and mortality. Our findings highlight the need to investigate and incorporate vulnerable populations in clinical trials.

Independent Effects of HIV and Antiretroviral Therapy on the Oral Microbiome Identified by Multivariate Analyses.

The oral microbiome is an important predictor of health and disease. We recently reported significant yet modest effects of HIV under highly active antiretroviral therapy (ART) on the oral microbiome (bacterial and fungal) in a large cohort of HIV-positive (HIV+) and matched HIV-negative (HIV-) individuals. As it was unclear whether ART added to or masked further effects of HIV on the oral microbiome, the present study aimed to analyze the effects of HIV and ART independently, which also included HIV- subjects on preexposure prophylaxis (PrEP) therapy. Cross-sectional analyses of the effect of HIV devoid of ART (HIV+ ART- versus matched HIV- subjects) showed a significant effect on both the bacteriome and mycobiome (P < 0.024) after controlling for other clinical variables (permutational multivariate analysis of variance [PERMANOVA] of Bray-Curtis dissimilarity). Cross-sectional analyses evaluating the effects of ART (HIV+ ART+ versus HIV+ ART- subjects) revealed a significant effect on the mycobiome (P < 0.007) but not the bacteriome. In parallel longitudinal analyses, ART (before versus after the initiation of ART) had a significant effect on the bacteriome, but not the mycobiome, of HIV+ and HIV- PrEP subjects (P < 0.005 and P < 0.016, respectively). These analyses also revealed significant differences in the oral microbiome and several clinical variables between HIV- PrEP subjects (pre-PrEP) and the HIV-matched HIV- group (P < 0.001). At the species level, a small number of differences in both bacterial and fungal taxa were identified within the effects of HIV and/or ART. We conclude that the effects of HIV and ART on the oral microbiome are similar to those of the clinical variables but collectively are modest overall. IMPORTANCE The oral microbiome can be an important predictor of health and disease. For persons living with HIV (PLWH), HIV and highly active antiretroviral therapy (ART) may have a significant influence on their oral microbiome. We previously reported a significant effect of HIV with ART on both the bacteriome and mycobiome. It was unclear whether ART added to or masked further effects of HIV on the oral microbiome. Hence, it was important to evaluate the effects of HIV and ART independently. For this, multivariate cross-sectional and longitudinal oral microbiome analyses (bacteriome and mycobiome) were conducted within the cohort, including HIV+ ART+ subjects and HIV+ and HIV- (preexposure prophylaxis [PrEP]) subjects before and after the initiation of ART. While we report independent significant effects of HIV and ART on the oral microbiome, we conclude that their influence is similar to that of the clinical variables but collectively modest overall.

Derivation and Validation of a Clinical Risk Assessment Model for Cancer-Associated Thrombosis in Two Unique US Health Care Systems.

PURPOSE: Venous thromboembolism (VTE), especially pulmonary embolism (PE) and lower extremity deep vein thrombosis (LE-DVT), is a serious and potentially preventable complication for patients with cancer undergoing systemic therapy. METHODS: Using retrospective data from patients diagnosed with incident cancer from 2011-2020, we derived a parsimonious risk assessment model (RAM) using least absolute shrinkage and selection operator regression from the Harris Health System (HHS, n = 9,769) and externally validated it using the Veterans Affairs (VA) health care system (n = 79,517). Bootstrapped c statistics and calibration curves were used to assess external model discrimination and fit. Dichotomized risk strata using integer scores were created and compared against the Khorana score (KS). RESULTS: Incident VTE and PE/LE-DVT at 6 months occurred in 590 (6.2%) and 437 (4.6%) patients in HHS and 4,027 (5.1%) and 3,331 (4.2%) patients in the VA health care system. Assessed at the time of systemic therapy initiation, the new RAM included components of the KS with the modified cancer subtype, cancer staging, systemic therapy class, history of VTE, history of paralysis/immobility, recent hospitalization, and Asian/Pacific Islander race. The c statistic was 0.71 in HHS and 0.68 in the VA health care system (compared with 0.65 and 0.60, respectively, for KS). Furthermore, the new RAM appropriately reclassified 28% of patients and increased the proportion of VTEs in the high-risk group from 37% to 68% in the validation data set. CONCLUSION: The novel RAM stratified patients with cancer into a high-risk group with 8%-10% cumulative incidence of VTE and 7% PE/LE-DVT at 6 months (v 3% and 2%, respectively, in the low-risk group). The model had improved performance over the original KS and doubled the number of VTE events in the high-risk stratum. We encourage additional external validation from prospective studies.[Media: see text].

Developing and optimizing a computable phenotype for incident venous thromboembolism in a longitudinal cohort of patients with cancer.

Background: Research on venous thromboembolism (VTE) that relies only on the International Classification of Diseases (ICD) can misclassify outcomes. Our study aims to discover and validate an improved VTE computable phenotype for people with cancer. Methods: We used a cancer registry electronic health record (EHR)-linked longitudinal database. We derived three algorithms that were ICD/medication based, natural language processing (NLP) based, or all combined. We then randomly sampled 400 patients from patients with VTE codes (n = 1111) and 400 from those without VTE codes (n = 7396). Weighted sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated on the entire sample using inverse probability weighting, followed by bootstrapped receiver operating curve analysis to calculate the concordance statistic (c statistic). Results: Among 800 patients sampled, 280 had a confirmed acute VTE during the first year after cancer diagnosis. The ICD/medication algorithm had a weighted PPV of 95% and a weighted sensitivity of 81%, with a c statistic of 0.90 (95% confidence interval [CI], 0.89-0.91). Adding Current Procedural Terminology codes for inferior vena cava filter removal or early death did not improve the performance. The NLP algorithm had a weighted PPV of 80% and a weighted sensitivity of 90%, with a c statistic of 0.93 (95% CI, 0.92-0.94). The combined algorithm had a weighted PPV of 98% at the higher cutoff and a weighted sensitivity of 96% at the lower cutoff, with a c statistic of 0.98 (95% CI, 0.97-0.98). Conclusions: Our ICD/medication-based algorithm can accurately identify VTE phenotype among patients with cancer with a high PPV of 95%. The combined algorithm should be considered in EHR databases that have access to such capabilities.

Effect of HIV/HAART and Other Clinical Variables on the Oral Mycobiome Using Multivariate Analyses.

The oral microbiome is considered an important factor in health and disease. We recently reported significant effects of HIV and several other clinical variables on the oral bacterial communities in a large cohort of HIV-positive and -negative individuals. The purpose of the present study was to similarly analyze the oral mycobiome in the same cohort. To identify fungi, the internal transcribed spacer 2 (ITS2) of the fungal rRNA genes was sequenced using oral rinse samples from 149 HIV-positive and 88 HIV-negative subjects that had previously undergone bacterial amplicon sequencing. Quantitative PCR was performed for total fungal content and total bacterial content. Interestingly, samples often showed predominance of a single fungal species with four major clusters predominated by Candida albicans, Candida dubliniensis, Malassezia restricta, or Saccharomyces cerevisiae Quantitative PCR analysis showed the Candida-dominated sample clusters had significantly higher total fungal abundance than the Malassezia or Saccharomyces species. Of the 25 clinical variables evaluated for potential influences on the oral mycobiome, significant effects were associated with caries status, geographical site of sampling, sex, HIV under highly active antiretroviral therapy (HAART), and missing teeth, in rank order of statistical significance. Investigating specific interactions between fungi and bacteria in the samples often showed Candida species positively correlated with Firmicutes or Actinobacteria and negatively correlated with Fusobacteria, Proteobacteria, and Bacteroidetes Our data suggest that the oral mycobiome, while diverse, is often dominated by a limited number of species per individual; is affected by several clinical variables, including HIV positivity and HAART; and shows genera-specific associations with bacterial groups.IMPORTANCE The oral microbiome is likely a key element of homeostasis in the oral cavity. With >600 bacterial species and >160 fungal species comprising the oral microbiome, influences on its composition can have an impact on both local and systemic health. We recently reported significant effects of HIV and several other clinical variables on the oral bacterial community in a large cohort of HIV-positive and -negative subjects. We describe here a comprehensive analysis of the oral mycobiome in the same cohort. Similar to the bacterial community, HIV under highly active antiretroviral therapy (HAART) had a significant impact on the mycobiome composition, but with less impact compared to other clinical variables. Additionally, unlike the oral bacterial microbiome, the oral mycobiome is often dominated by a single species with 4 major clusters of fungal communities. Together, these results suggest the oral mycobiome has distinct properties compared with the oral bacterial community, although both are equally impacted by HIV.

Significant effect of HIV/HAART on oral microbiota using multivariate analysis.

Persons infected with HIV are particularly vulnerable to a variety of oral microbial diseases. Although various study designs and detection approaches have been used to compare the oral microbiota of HIV-negative and HIV-positive persons, both with and without highly active antiretroviral therapy (HAART), methods have varied, and results have not been consistent or conclusive. The purpose of the present study was to compare the oral bacterial community composition in HIV-positive persons under HAART to an HIV-negative group using 16S rRNA gene sequence analysis. Extensive clinical data was collected, and efforts were made to balance the groups on clinical variables to minimize confounding. Multivariate analysis was used to assess the independent contribution of HIV status. Eighty-nine HIV-negative participants and 252 HIV-positive participants under HAART were sampled. The independent effect of HIV under HAART on the oral microbiome was statistically significant, but smaller than the effect of gingivitis, periodontal disease, smoking, caries, and other clinical variables. In conclusion, a multivariate comparison of a large sample of persons with HIV under HAART to an HIV-negative control group showed a complex set of clinical features that influenced oral bacterial community composition, including the presence of HIV under HAART.

Paro cardiorrespiratorio prehospitalario: Desfibrilación de acceso público / Prehospital Cardiac Arrest: Public-Access Defibrillation / Prehospital Cardiac Arrest: Public-Access Defibrillation

La enfermedad cardiovascular es la principal causa de muerte en países de concentración urbana como el nuestro. La mayoría de esas muertes se producirán en el ámbito prehospitalario y sólo una rápida respuesta con maniobras de resucitación cardiopulmonar y desfibrilación precoz puede lograr una sobrevida aceptable. En esta presentación se describe el caso de un individuo que sufrió un paro cardiorrespiratorio mientras circulaba por la vía pública y que fue rescatado exitosamente gracias a la desfibrilación precoz realizada con un desfibrilador externo automático. Se incluyen los registros gráficos del evento y se enfatizan consideraciones sobre la importancia del concepto de acceso público a la desfibrilación.

Cardiovascular disease is the leading cause of death in countries like ours with urban areas. Most of these deaths occur in the prehospital setting and a rapid response with cardiopulmonary resuscitation and early defibrillation are necessary to maximize survival. We describe the case of a subject who suffered a cardiac arrest while walking in the public thoroughfare and was successfully resuscitated with early defibrillation using and automated external defibrillator. The electrocardiograms obtained during the episode are included and the importance of the concept of public access defibrillation is emphasized.

Informe sobre los ensayos clínicos farmacológicos en cardiología realizados en la Argentina entre 2006 y 2010 / Clinical Trials in Cardiovascular Pharmacology in Argentina Between 2006 and 2010 / Clinical Trials in Cardiovascular Pharmacology in Argentina Between 2006 and 2010

Con el objetivo de analizar las características de los ensayos clínicos farmacológicos patrocinados por la industria en el área de las enfermedades cardiovasculares en la Argentina, se efectuó una búsqueda de los estudios farmacológicos realizados en el área de la cardiología, autorizados por la ANMAT entre 2006 y 2010, mediante la base de datos pública de dicho organismo. De 1.003 ensayos aprobados en ese período, 120 (11,9%) pertenecían al área de las enfermedades cardiovasculares. Se observó una reducción en términos absolutos del número de estudios entre 2006 y 2010 (r = 0,79), tendencia que se contrapuso al aumento de los ensayos clínicos observado en otras especialidades. De los 120 estudios analizados, el 68,3% pertenecían a ensayos sobre hipertensión, enfermedad coronaria, enfermedad vascular periférica o fibrilación auricular. Del total de centros participantes, el 87% correspondió a entidades privadas y sólo el 13% a hospitales comunitarios o públicos. Casi la totalidad de los estudios correspondieron a las fases II y III de investigación clínica y sólo dos comités de bioética fueron responsables de la aprobación de casi el 95% de los ensayos. En conclusión, los estudios del área cardiovascular han mostrado una reducción en su número absoluto y relativo con respecto a otras áreas. Pese a ello, la Argentina mantiene el segundo puesto en cantidad de ensayos cardiovasculares detrás de Brasil, aunque con una injerencia mayor de las organizaciones de investigación clínica y una participación menor de los hospitales públicos. La alta concentración de aprobaciones de estudios en sólo dos comités de bioética impediría un control adecuado de la evolución de los protocolos.

We conducted a survey of pharmacological studies in the cardiovascular area to analyze the characteristics of clinical trials of cardiovascular diseases sponsored by pharmaceutical companies in Argentina. The studies included had been authorized by the ANMAT between 2006 and 2010. The information was retrieved from the ANMAT database. Of 1003 trials approved over that period, 120 (11.9%) belonged to the cardiovascular area. The number of studies decreased between 2006 and 2010 (r=0.79) as opposed to the increase observed in the number of clinical trials in other specialties. A total of 120 studies were analyzed; 68.3% were trials on hypertension, coronary artery disease, peripheral vascular disease or atrial fibrillation. Eighty seven percent of the participant centers were private institutions and only 13% were community- or public hospitals. Almost all the studies corresponded to clinical trials in phase II and III. Only two bioethics committees were responsible for the approval of almost 95% of trials. In conclusion, we found a reduction in the absolute and relative number of cardiovascular studies compared to other specialties. Nevertheless, Argentina remains in the second place behind Brazil in the number of clinical trials in the cardiovascular area, although the participation of clinical research organizations was higher and that of public hospitals was very low. The fact that only two bioethics committees were responsible for the approval of most studies might prevent an adequate monitoring of study outcomes.

Paro cardiorrespiratorio prehospitalario: Desfibrilación de acceso público / Prehospital Cardiac Arrest: Public-Access Defibrillation / Prehospital Cardiac Arrest: Public-Access Defibrillation

La enfermedad cardiovascular es la principal causa de muerte en países de concentración urbana como el nuestro. La mayoría de esas muertes se producirán en el ámbito prehospitalario y sólo una rápida respuesta con maniobras de resucitación cardiopulmonar y desfibrilación precoz puede lograr una sobrevida aceptable. En esta presentación se describe el caso de un individuo que sufrió un paro cardiorrespiratorio mientras circulaba por la vía pública y que fue rescatado exitosamente gracias a la desfibrilación precoz realizada con un desfibrilador externo automático. Se incluyen los registros gráficos del evento y se enfatizan consideraciones sobre la importancia del concepto de acceso público a la desfibrilación.(AU)

Cardiovascular disease is the leading cause of death in countries like ours with urban areas. Most of these deaths occur in the prehospital setting and a rapid response with cardiopulmonary resuscitation and early defibrillation are necessary to maximize survival. We describe the case of a subject who suffered a cardiac arrest while walking in the public thoroughfare and was successfully resuscitated with early defibrillation using and automated external defibrillator. The electrocardiograms obtained during the episode are included and the importance of the concept of public access defibrillation is emphasized.(AU)

Informe sobre los ensayos clínicos farmacológicos en cardiología realizados en la Argentina entre 2006 y 2010 / Clinical Trials in Cardiovascular Pharmacology in Argentina Between 2006 and 2010 / Clinical Trials in Cardiovascular Pharmacology in Argentina Between 2006 and 2010

Con el objetivo de analizar las características de los ensayos clínicos farmacológicos patrocinados por la industria en el área de las enfermedades cardiovasculares en la Argentina, se efectuó una búsqueda de los estudios farmacológicos realizados en el área de la cardiología, autorizados por la ANMAT entre 2006 y 2010, mediante la base de datos pública de dicho organismo. De 1.003 ensayos aprobados en ese período, 120 (11,9%) pertenecían al área de las enfermedades cardiovasculares. Se observó una reducción en términos absolutos del número de estudios entre 2006 y 2010 (r = 0,79), tendencia que se contrapuso al aumento de los ensayos clínicos observado en otras especialidades. De los 120 estudios analizados, el 68,3% pertenecían a ensayos sobre hipertensión, enfermedad coronaria, enfermedad vascular periférica o fibrilación auricular. Del total de centros participantes, el 87% correspondió a entidades privadas y sólo el 13% a hospitales comunitarios o públicos. Casi la totalidad de los estudios correspondieron a las fases II y III de investigación clínica y sólo dos comités de bioética fueron responsables de la aprobación de casi el 95% de los ensayos. En conclusión, los estudios del área cardiovascular han mostrado una reducción en su número absoluto y relativo con respecto a otras áreas. Pese a ello, la Argentina mantiene el segundo puesto en cantidad de ensayos cardiovasculares detrás de Brasil, aunque con una injerencia mayor de las organizaciones de investigación clínica y una participación menor de los hospitales públicos. La alta concentración de aprobaciones de estudios en sólo dos comités de bioética impediría un control adecuado de la evolución de los protocolos.(AU)

We conducted a survey of pharmacological studies in the cardiovascular area to analyze the characteristics of clinical trials of cardiovascular diseases sponsored by pharmaceutical companies in Argentina. The studies included had been authorized by the ANMAT between 2006 and 2010. The information was retrieved from the ANMAT database. Of 1003 trials approved over that period, 120 (11.9%) belonged to the cardiovascular area. The number of studies decreased between 2006 and 2010 (r=0.79) as opposed to the increase observed in the number of clinical trials in other specialties. A total of 120 studies were analyzed; 68.3% were trials on hypertension, coronary artery disease, peripheral vascular disease or atrial fibrillation. Eighty seven percent of the participant centers were private institutions and only 13% were community- or public hospitals. Almost all the studies corresponded to clinical trials in phase II and III. Only two bioethics committees were responsible for the approval of almost 95% of trials. In conclusion, we found a reduction in the absolute and relative number of cardiovascular studies compared to other specialties. Nevertheless, Argentina remains in the second place behind Brazil in the number of clinical trials in the cardiovascular area, although the participation of clinical research organizations was higher and that of public hospitals was very low. The fact that only two bioethics committees were responsible for the approval of most studies might prevent an adequate monitoring of study outcomes.(AU)