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1.
Epidemiology ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39316830

RESUMEN

BACKGROUND: Intersectionality, or the multidimensional influence of social identity and systems of power, may drive increased morbidity and mortality for adults of color with Down syndrome. We documented racial and ethnic differences in death and hospitalizations among Medicaid enrolled adults with Down syndrome and assessed interaction of racial-ethnic group and Down syndrome. METHODS: Our sample consisted of 119,325 adults with Down syndrome and >3.2 million adults without intellectual disability enrolled in Medicare at any point from 2011-2019. We calculated age-adjusted mortality and hospitalization rates by racial-ethnic group among those with Down syndrome. We examined additive interaction between Down syndrome and racial and ethnic group on mortality and hospitalization rates. RESULTS: Among those with Down syndrome, age-adjusted mortality rate did not differ between Black and White racial groups (rate ratio: 0.96, 95%CI: 0.92, 1.01) while mortality rate was lower for Pacific Islander (0.80), Asian (0.71), Native (0.77), and Mixed-race groups (0.50). Hospitalization rates were higher for all marginalized groups compared to the White group. When assessing the interaction between racial-ethnic group and Down syndrome, Black, Native Americans, and Mixed-race groups exhibited a negative additive interaction for mortality rate and all groups except Native Americans exhibited positive additive interaction for hospitalization. CONCLUSIONS: Increased hospitalization rates for adults with Down syndrome from marginalized racial and ethnic groups suggest worse health and healthcare. Similar mortality rates across racial and ethnic groups may result from increased infant mortality rate in marginalized groups with Down syndrome leading to reduced mortality among those surviving to adulthood.

2.
Occup Environ Med ; 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39327042

RESUMEN

OBJECTIVES: To estimate the impact of occupational injury and illness on opioid-related mortality while accounting for confounding by preinjury opioid use. METHODS: We employed a retrospective cohort study design using Washington State workers' compensation data for 1994-2000 injuries linked to US Social Security Administration earnings and mortality data and National Death Index (NDI) cause of death data from 1994 to 2018. We categorised injuries as lost-time versus medical-only, where the former involved more than 3 days off work or permanent disability. We determined death status and cause of death from NDI records. We modelled separate Fine and Gray subdistribution hazard ratios (sHRs) and 95% CIs for injured men and women for opioid-related and all drug-related mortality through 2018. We used quantitative bias analysis to account for unmeasured confounding by preinjury opioid use. RESULTS: The hazard of opioid-related mortality was elevated for workers with lost-time relative to medical-only injuries: sHR for men: 1.53, 95% CI 1.41 to 1.66; for women: 1.31, 95% CI 1.16 to 1.48. Accounting for preinjury opioid use, effect sizes were reduced but remained elevated: sHR for men was 1.43, 95% simulation interval (SI) 1.20 to 1.69; for women: 1.27, 95% SI 1.10 to 1.45. CONCLUSIONS: Occupational injuries and illnesses severe enough to require more than 3 days off work are associated with an increase in the hazard of opioid-related mortality. The estimated increase is reduced when we account for preinjury opioid use, but it remains substantial. Reducing work-related injuries and postinjury opioid prescribing and improving employment and income security may decrease opioid-related mortality.

3.
JAMA Netw Open ; 7(9): e2435018, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39312235

RESUMEN

Importance: With the advancement in administrative data as a research tool and the reliance on public health insurance for individuals with Down syndrome, population-level trends in Alzheimer dementia in this population are beginning to be understood. Objective: To comprehensively describe the epidemiology of Alzheimer dementia in adults with Down syndrome in a full US Medicare and Medicaid sample. Design, Setting, and Participants: This cohort study included 132 720 adults aged 18 years or older with Medicaid and/or Medicare claims data with an International Statistical Classification of Diseases and Related Health Problems code for Down syndrome. Data were collected from January 1, 2011, to December 31, 2019, and analyzed from August 2023 to May 2024. Main Outcomes and Measures: The main outcome was prevalence of Alzheimer dementia in each calendar year and during the 9-year period. Alzheimer dementia incidence rates by calendar year and age and stratified for race or ethnicity as well as time to death after Alzheimer dementia diagnosis were also assessed. Results: There were 132 720 unique adults with Down syndrome from 2011 to 2019: 79 578 (53.2%) were male, 17 090 (11.7%) were non-Hispanic Black, 20 777 (15.7%) were Hispanic, 101 120 (68.8%) were non-Hispanic White, and 47 692 (23.3%) had ever had an Alzheimer dementia diagnosis. Incidence was 22.4 cases per 1000 person-years. The probability of an incident Alzheimer dementia diagnosis over 8 years was 0.63 (95% CI, 0.62-0.64) for those entering the study between ages 55 to 64 years. Mean (SD) age at incident diagnosis was 54.5 (7.4) years and median (IQR) age was 54.6 (9.3) years. Mean (SD) age at death among those with Alzheimer dementia was 59.2 (6.9) years (median [IQR], 59.0 [8.0] years). The mean (SD) age at onset for the Hispanic group was 54.2 (9.2) years, 52.4 (7.8) years for the American Indian or Alaska Native group, and 52.8 (8.2) years for the mixed race groups compared with 55.0 (7.8) years for the White non-Hispanic group. For age at death, there were no differences by sex. The mean (SD) age at death was later for the White non-Hispanic group (59.3 [6.8] years) compared with the Hispanic group (58.5 [7.8] years), Native American group (57.8 [7.1] years), and mixed race group (58.2 [7.0] years). Conclusions and Relevance: In this cohort study of adults with Down syndrome who were enrolled in Medicaid and Medicare, Alzheimer dementia occurred at high rates. Consistency with clinical studies of dementia in Down syndrome supports the use of administrative data in Down syndrome-Alzheimer dementia research.


Asunto(s)
Enfermedad de Alzheimer , Síndrome de Down , Humanos , Síndrome de Down/epidemiología , Síndrome de Down/complicaciones , Enfermedad de Alzheimer/epidemiología , Masculino , Femenino , Estados Unidos/epidemiología , Persona de Mediana Edad , Anciano , Adulto , Medicare/estadística & datos numéricos , Estudios de Cohortes , Medicaid/estadística & datos numéricos , Prevalencia , Incidencia , Anciano de 80 o más Años , Adolescente , Adulto Joven
4.
PLOS Glob Public Health ; 4(9): e0002127, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39236028

RESUMEN

ART scale-up has reduced HIV mortality in South Africa. However, less is known about trends in hospital-based HIV care, which is costly and may indicate HIV-related morbidity. We assessed trends in hospital-based HIV care using the National Health Laboratory Service (NHLS) National HIV Cohort. Our study included all adults ≥18 years receiving care in South Africa's public sector HIV program from 2004 to 2017 with at least one CD4 count/viral load test in the NHLS database. We compared trends in the number of patients presenting for and receiving HIV care by facility type: hospitals vs. primary care clinics. We then assessed trends and predictors of incident hospitalization, defined as 2 or more hospital-based lab tests taken within 7 days. Finally, we assessed whether trends in incident hospitalizations could be explained by changes in patient demographics, CD4 counts, or facility type at presentation. Data were analyzed on 9,624,951 patients. The percentage of patients presenting and receiving HIV care at hospitals (vs. clinics) declined over time, from approximately 60% in 2004 to 15% in 2017. Risk of hospitalization declined for patients entering care between 2004-2012 and modestly increased for patients entering care after 2012. The risk of hospitalization declined the most in age groups most affected by HIV. Over time, patients presented with higher CD4 counts and were more likely to present at clinics, and these changes explained almost half the decline in hospitalizations. The percentage of HIV care provided in hospitals declined as patients presented in better health and as treatment was increasingly managed at clinics. However, there may still be opportunities to reduce incident hospitalizations in people with HIV.

5.
Am J Epidemiol ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39289169

RESUMEN

In 1965, Sir Austin Bradford Hill articulated nine viewpoints for evaluating whether a body of evidence about the relationship between an exposure and outcome should be interpreted causally. In this commentary, we highlight a selection of the ways in which these viewpoints have had an impact on the field of epidemiology in terms of methods development, study design, and interpretation of results. Additionally, we opine on how the viewpoints relate to our understanding of basic epidemiologic concepts - for example, our choice of absolute or relative measures of effect, our evolving understanding of the role of context in the generalizability of study results, and modern epistemologies for causal inference (i.e., the potential outcomes framework and graphical causal models). Hill cautioned his audience that evidence should be weighed according to the policy choice it would inform and the context in which that policy would be implemented. We root our remarks in considerations of the public health impact of our conclusions about the causal nature of an observed relationship.

7.
Artículo en Inglés | MEDLINE | ID: mdl-39169475

RESUMEN

BACKGROUND: The target trial framework was developed as a strategy to design and analyze observational epidemiologic studies with the aim of reducing bias due to analytic decisions. It involves designing a hypothetical randomized trial to answer a question of interest and systematically considering how to use observational data to emulate each trial component. AIMS: The primary aim of this paper is to provide a detailed example of the application of the target trial framework to a research question in oral epidemiology. MATERIALS AND METHODS: We describe the development of a hypothetical target trial and emulation protocol to evaluate the effect of preconception periodontitis treatment on time-to-pregnancy. We leverage data from Pregnancy Study Online (PRESTO), a preconception cohort, to ground our example in existing observational data. We discuss the decision-making process for each trial component, as well as limitations encountered. RESULTS: Our target trial application revealed data limitations that precluded us from carrying out the proposed emulation. Implications for data quality are discussed and we provide recommendations for researchers interested in conducting trial emulations in the field of oral epidemiology. DISCUSSION: The target trial framework has the potential to improve the validity of observational research in oral health, when properly applied. CONCLUSION: We encourage the broad adoption of the target trial framework to the field of observational oral health research and demonstrate its value as a tool to identify directions for future research.

8.
Am J Epidemiol ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39191652

RESUMEN

Quality mentoring improves outcomes across career stages, including a sense of belonging, persistence, and productivity. However, the status quo in mentorship culture-including in epidemiology-is an ad hoc approach. This pervasive culture adversely affects individual mentees and the entire scientific research enterprise. Public health disciplines such as epidemiology bear a distinct responsibility to foster an inclusive mentorship culture, ensuring the next generation is equipped not only with methodological expertise but also with a commitment to diversity, equity, inclusion, and the principles of public health. In this commentary, we outline the primary attributes of effective mentors, core competencies, and the evidence base underlying how mentors can improve their skills with comprehensive training. We call on mentors, as well as institutional leaders, to make personal and structural changes, such as requiring mentor training, implementing evidence-based tools (e.g., individual development plans), and regularly evaluating mentorship quality. Institutional leaders can remove barriers (e.g., costs to enroll in mentor training) and facilitate mentorship in non-monetary ways, for example, by making it a formal part of the promotion process. Mentors and leaders must champion these changes, fortifying not only individual career trajectories but also advancing scientific integrity, inclusivity, and justice within the epidemiologic community.

9.
Clin Epidemiol ; 16: 501-512, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39081306

RESUMEN

Background: Observational studies of SARS-CoV-2 vaccine effectiveness are prone to confounding, which can be illustrated using negative control methods. Methods: Nationwide population-based cohort study including two cohorts of Danish residents 60-90 years of age matched 1:1 on age and sex: A vaccinated and a non-vaccinated cohort, including 61052 SARS-CoV-2 vaccinated individuals between 1 March and 1 July 2021 and 61052 individuals not vaccinated preceding 1 July 2021. From these two cohorts, we constructed negative control cohorts of individuals diagnosed with SARS-CoV-2 infection or acute myocardial infarction, stroke, cancer, low energy fracture, or head-trauma. Outcomes were SARS-CoV-2 infection, negative control outcomes (eg, mammography, prostate biopsy, operation for cataract, malignant melanoma, examination of eye and ear), and death. We used Cox regression to calculate adjusted incidence and mortality rate ratios (aIRR and aMRR). Results: Risks of SARS-CoV2 infection and all negative control outcomes were elevated in the vaccinated population, ranging from an aIRR of 1.15 (95% CI: 1.09-1.21) for eye examinations to 3.05 (95% CI: 2.24-4.14) for malignant melanoma. Conversely, the risk of death in the SARS-CoV-2 infected cohort and in all negative control cohorts was lower in vaccinated individuals, ranging from an aMRR of 0.23 (95% CI: 0.19-0.26) after SARS-CoV-2 infection to 0.50 (95% CI: 0.37-0.67) after stroke. Conclusion: Our findings indicate that observational studies of SARS-CoV-2 vaccine effectiveness may be subject to substantial confounding. Therefore, randomized trials are essential to establish vaccine efficacy after the emergence of new SARS-CoV-2 variants and the rollout of multiple booster vaccines.


Why was this study done: : After the emergence of new SARS-CoV-2 variants and the rollout of multiple booster SARS-CoV-2 vaccines, the impact of vaccination on risk of SARS-CoV-2 infection and death after the infection has mainly been explored in observational studies. We used negative control methods to investigate whether confounding affects the results of observational SARS-CoV-2 vaccine effectiveness studies. Findings: : We used Danish registry data obtained during the SARS-CoV-2 vaccine roll-out to conduct a nationwide, matched population-based cohort study of Danish residents 60­90 years in which we compared vaccinated individuals with non-vaccinated individuals. Compared with unvaccinated individuals, vaccinated individuals had increased risks of SARS-CoV2 infection but also had increased risks of all negative control outcomes (mammography, prostate biopsy, operation for cataract, malignant melanoma, examination of eye and ear). The risk of death after SARS-CoV2 infection was lower in the vaccinated cohort, as was the risk of death after acute myocardial infarction, stroke, cancer, low energy fracture, and head-trauma. Meaning: : The negative control methods indicate that observational studies of SARS-CoV-2 vaccine effectiveness may be prone to substantial confounding which may impact the observed associations. This bias may both lead to underestimation of vaccine effectiveness (increased risk of SARS-CoV2 infection among vaccinated individuals) and overestimation of the vaccine effectiveness (decreased risk of death after of SARS-CoV2 infection among vaccinated individuals). Our results highlight the need for randomized vaccine efficacy studies after the emergence of new SARS-CoV-2 variants and the rollout of multiple booster vaccines.

10.
J Sex Med ; 21(9): 800-806, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39034042

RESUMEN

BACKGROUND: Vulvodynia impacts up to 8% of women by age 40, and these women may have a more compromised immune system than women with no vulvar pain history. AIM: Given that psychiatric morbidity is associated with vulvodynia and is known to activate immune inflammatory pathways in the brain and systemically, we sought to determine whether the association between psychiatric morbidity and vulvar pain was independent of or dependent upon the presence of immune-related conditions. METHODS: Women born in Sweden between 1973 and 1996 with localized provoked vulvodynia (N76.3) and/or vaginismus (N94.2 or F52.5) diagnosed between 2001 and 2018 were matched to two women from the same birth year with no vulvar pain. International Statistical Classification of Diseases and Related Health Problems (ICD-9 or -10 codes) were used to identify women with a history of depression, anxiety, attempted suicide, neurotic disorders, stress-related disorders, behavioral syndromes, personality disorders, psychotic disorders, or chemical dependencies, as well as a spectrum of immune-related conditions. The Swedish National Prescribed Drug Register was used to identify women with filled prescriptions of antidepressants or anxiolytics. OUTCOMES: Vulvodynia, vaginismus, or both were outcomes assessed in relation to psychiatric morbidity. RESULTS: Women with vulvodynia, vaginismus, or both, relative to those without vulvar pain, had adjusted odds ratios between 1.4 and 2.3, with CIs highly compatible with harmful effects. When we assessed women with and those without a lifetime history of immune-related conditions separately, we also observed elevated odds ratios in both groups for mood, anxiety, and neurotic and stress disorders. CLINICAL IMPLICATIONS: Documenting psychiatric impairment as a cause or consequence of vulvodynia is critical in clinical practice because psychiatric conditions may impact treatment efficacy. STRENGTHS AND LIMITATIONS: Strengths of this study include a data source that represents the entire population of women in Sweden that is known to be highly accurate because Sweden provides universal healthcare. Limitations include difficulty in making an accurate assessment of temporality between psychiatric morbidity and the first onset of vulvar pain. In addition, because Swedish registry data have limited information on lifestyle, behavioral, and anthropomorphic factors such as smoking, diet, physical activity, and obesity, these conditions could not be assessed as confounders of psychiatric morbidity and vulvar pain. CONCLUSIONS: Immune pathways by which women with psychiatric conditions increase their risk of vulvar pain could be independent from other immune pathways.


Asunto(s)
Vulvodinia , Humanos , Femenino , Vulvodinia/epidemiología , Vulvodinia/inmunología , Suecia/epidemiología , Adulto , Vaginismo/epidemiología , Trastornos Mentales/epidemiología , Sistema de Registros , Adulto Joven , Estudios de Casos y Controles
11.
ArXiv ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38827461

RESUMEN

Virtual staining streamlines traditional staining procedures by digitally generating stained images from unstained or differently stained images. While conventional staining methods involve time-consuming chemical processes, virtual staining offers an efficient and low infrastructure alternative. Leveraging microscopy-based techniques, such as confocal microscopy, researchers can expedite tissue analysis without the need for physical sectioning. However, interpreting grayscale or pseudo-color microscopic images remains a challenge for pathologists and surgeons accustomed to traditional histologically stained images. To fill this gap, various studies explore digitally simulating staining to mimic targeted histological stains. This paper introduces a novel network, In-and-Out Net, specifically designed for virtual staining tasks. Based on Generative Adversarial Networks (GAN), our model efficiently transforms Reflectance Confocal Microscopy (RCM) images into Hematoxylin and Eosin (H&E) stained images. We enhance nuclei contrast in RCM images using aluminum chloride preprocessing for skin tissues. Training the model with virtual H\&E labels featuring two fluorescence channels eliminates the need for image registration and provides pixel-level ground truth. Our contributions include proposing an optimal training strategy, conducting a comparative analysis demonstrating state-of-the-art performance, validating the model through an ablation study, and collecting perfectly matched input and ground truth images without registration. In-and-Out Net showcases promising results, offering a valuable tool for virtual staining tasks and advancing the field of histological image analysis.

12.
Eur J Nucl Med Mol Imaging ; 51(11): 3176-3190, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38722382

RESUMEN

Chimeric antigen receptor (CAR) cell therapies utilize CARs to redirect immune cells towards cancer cells expressing specific antigens like human epidermal growth factor receptor 2 (HER2). Despite their potential, CAR T cell therapies exhibit variable response rates and adverse effects in some patients. Non-invasive molecular imaging can aid in predicting patient outcomes by tracking infused cells post-administration. CAR-T cells are typically autologous, increasing manufacturing complexity and costs. An alternative approach involves developing CAR natural killer (CAR-NK) cells as an off-the-shelf allogeneic product. In this study, we engineered HER2-targeted CAR-NK cells co-expressing the positron emission tomography (PET) reporter gene human sodium-iodide symporter (NIS) and assessed their therapeutic efficacy and PET imaging capability in a HER2 ovarian cancer mouse model.NK-92 cells were genetically modified to express a HER2-targeted CAR, the bioluminescence imaging reporter Antares, and NIS. HER2-expressing ovarian cancer cells were engineered to express the bioluminescence reporter Firefly luciferase (Fluc). Co-culture experiments demonstrated significantly enhanced cytotoxicity of CAR-NK cells compared to naive NK cells. In vivo studies involving mice with Fluc-expressing tumors revealed that those treated with CAR-NK cells exhibited reduced tumor burden and prolonged survival compared to controls. Longitudinal bioluminescence imaging demonstrated stable signals from CAR-NK cells over time. PET imaging using the NIS-targeted tracer 18F-tetrafluoroborate ([18F]TFB) showed significantly higher PET signals in mice treated with NIS-expressing CAR-NK cells.Overall, our study showcases the therapeutic potential of HER2-targeted CAR-NK cells in an aggressive ovarian cancer model and underscores the feasibility of using human-derived PET reporter gene imaging to monitor these cells non-invasively in patients.


Asunto(s)
Células Asesinas Naturales , Neoplasias Ováricas , Tomografía de Emisión de Positrones , Receptor ErbB-2 , Receptores Quiméricos de Antígenos , Simportadores , Femenino , Humanos , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/terapia , Neoplasias Ováricas/metabolismo , Animales , Simportadores/metabolismo , Simportadores/genética , Receptor ErbB-2/metabolismo , Ratones , Tomografía de Emisión de Positrones/métodos , Línea Celular Tumoral , Células Asesinas Naturales/metabolismo , Receptores Quiméricos de Antígenos/metabolismo
13.
Am J Epidemiol ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38754869

RESUMEN

We spend a great deal of time on confounding in our teaching, in our methods development and in our assessment of study results. This may give the impression that uncontrolled confounding is the biggest problem that observational epidemiology faces, when in fact, other sources of bias such as selection bias, measurement error, missing data, and misalignment of zero time may often (especially if they are all present in a single study) lead to a stronger deviation from the truth. Compared to the amount of time we spend teaching how to address confounding in a data analysis, we spend relatively little time teaching methods for simulating confounding (and other sources of bias) to learn their impact and develop plans to mitigate or quantify the bias. We review a paper by Desai et al that uses simulation methods to quantify the impact of an unmeasured confounder when it is completely missing or when a proxy of the confounder is measured. We use this article to discuss how we can use simulations of sources of bias to ensure we generate better and more valid study estimates, and we discuss the importance of simulating realistic datasets with plausible bias structures to guide data collection. If an advanced life form exists outside of our current universe and they came to earth with the goal of scouring the published epidemiologic literature to understand what the biggest problem epidemiologists have, they would quickly discover that the limitations section of publications would provide them with all the information they needed. And most likely what they would conclude is that the biggest problem that we face is uncontrolled confounding. It seems to be an obsession of ours.

14.
AIDS ; 38(8): 1198-1205, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38814712

RESUMEN

OBJECTIVE: To estimate the relative rate of all-cause mortality amongst those on antiretroviral treatment (ART) with a history of interruptions compared with those with no previous interruptions in care. DESIGN: Retrospective cohort study. METHODS: We used data from four South African cohorts participating in the International epidemiology Databases to Evaluate AIDS Southern Africa collaboration. We included adults who started ART between 2004 and 2019. We defined a care interruption as a gap in contact longer than 180 days. Observation time prior to interruption was allocated to a 'no interruption' group. Observation time after interruption was allocated to one of two groups based on whether the first interruption started before 6 months of ART ('early interruption') or later ('late interruption'). We used Cox regression to estimate hazard ratios. RESULTS: Sixty-three thousand six hundred and ninety-two participants contributed 162 916 person-years of observation. There were 3469 deaths. Most participants were female individuals (67.4%) and the median age at ART initiation was 33.3 years (interquartile range: 27.5-40.7). Seventeen thousand and eleven (26.7%) participants experienced care interruptions. Those resuming ART experienced increased mortality compared with those with no interruptions: early interrupters had a hazard ratio of 4.37 (95% confidence interval (CI) 3.87-4.95) and late interrupters had a hazard ratio of 2.74 (95% CI 2.39-3.15). In sensitivity analyses, effect sizes were found to be proportional to the length of time used to define interruptions. CONCLUSION: Our findings highlight the need to improve retention in care, regardless of treatment duration. Programmes to encourage return to care also need to be strengthened.


Asunto(s)
Infecciones por VIH , Humanos , Femenino , Masculino , Estudios Retrospectivos , Adulto , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/mortalidad , Sudáfrica/epidemiología , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Persona de Mediana Edad , Antirretrovirales/uso terapéutico
16.
Pharmacoepidemiol Drug Saf ; 33(5): e5796, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38680093

RESUMEN

PURPOSE: Use of real-world data (RWD) for external controls added to single-arm trials (SAT) is increasingly prevalent in regulatory submissions. Due to inherent differences in the data-generating mechanisms, biases can arise. This paper aims to illustrate how to use quantitative bias analysis (QBA). METHODS: Advanced non-small cell lung cancer (NSCLC) serves as an example, where many small subsets of patients with molecular tumor subtypes exist. First, some sources of bias that may occur in oncology when comparing RWD to SAT are described. Second, using a hypothetical immunotherapy agent, a dataset is simulated based on expert input for survival analysis of advanced NSCLC. Finally, we illustrate the impact of three biases: missing confounder, misclassification of exposure, and outcome evaluation. RESULTS: For each simulated scenario, bias was induced by removing or adding data; hazard ratios (HRs) were estimated applying conventional analyses. Estimating the bias-adjusted treatment effect and uncertainty required carefully selecting the bias model and bias factors. Although the magnitude of each biased and bias-adjusted HR appeared moderate in all three hypothetical scenarios, the direction of bias was variable. CONCLUSION: These findings suggest that QBA can provide an intuitive framework for bias analysis, providing a key means of challenging assumptions about the evidence. However, the accuracy of bias analysis is itself dependent on correct specification of the bias model and bias factors. Ultimately, study design should reduce bias, but QBA allows us to evaluate the impact of unavoidable bias to assess the quality of the evidence.


Asunto(s)
Sesgo , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/terapia , Proyectos de Investigación , Ensayos Clínicos como Asunto/métodos , Simulación por Computador , Análisis de Supervivencia , Inmunoterapia/métodos
17.
Aliment Pharmacol Ther ; 59(12): 1551-1558, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38597407

RESUMEN

BACKGROUND: Paediatric-onset immune-mediated inflammatory diseases (pIMID) show more aggressive phenotypes than when diagnosed in adults. However, data on mortality are often extrapolated from adult studies. AIM: To estimate the effect of pIMID on mortality. METHODS: In a population-based cohort study using the nationwide Danish healthcare registers, we included all patients diagnosed with pIMID in Denmark from 1980 to 2018. PIMID were defined as ICD codes indicative of autoimmune hepatitis, primary sclerosing cholangitis, Crohn's disease, ulcerative colitis, juvenile idiopathic arthritis, lupus erythematosus, or vasculitis registered before age 18 years. All-cause mortality was the primary outcome; cause-specific mortality was the secondary outcome. We used Cox survival analysis to estimate hazard ratios (HR), and Aalen survival analysis to estimate rate differences. RESULTS: We included 11,581 individuals diagnosed with pIMID and 99,665 reference individuals, accounting for 1,371,994 person-years of follow-up. Median and interquartile (IQR) age at diagnosis was 12.6 (7.9-15.9) years. During follow-up, 152 patients with pIMID and 316 reference individuals died; adjusted HR (aHR) was 3.8 (95% confidence interval [CI] 3.1-4.7). This corresponded to 6.9 (95% CI: 5.3-8.5) additional deaths per 10,000 person-years. The strongest associations were found for gastrointestinal diseases (aHR 22.8; 95% CI 9.6-64.1), gastrointestinal cancers (aHR 19.2; 95% CI 5.0-74.2) and lymphoproliferative disorders (aHR 6.8; 95% CI 2.8-16.8). CONCLUSION: Patients diagnosed with pIMID have a fourfold higher risk of mortality when followed into early adulthood compared with reference individuals. This underlines the severe disease course of pIMID and highlights the need for multidisciplinary care.


Asunto(s)
Sistema de Registros , Humanos , Masculino , Femenino , Niño , Adolescente , Dinamarca/epidemiología , Estudios de Cohortes , Factores de Riesgo , Edad de Inicio , Preescolar , Causas de Muerte , Inflamación/mortalidad
18.
AIDS Behav ; 28(2): 591-608, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38300475

RESUMEN

Low- and middle-income countries are facing a growing burden of noncommunicable diseases (NCDs). Providing HIV treatment may provide opportunities to increase access to NCD services in under-resourced environments. We conducted a systematic review and meta-analysis to evaluate whether use of antiretroviral therapy (ART) was associated with increased screening, diagnosis, treatment, and control of diabetes, hypertension, chronic kidney disease, or cardiovascular disease among people living with HIV in sub-Saharan Africa (SSA). A comprehensive search of electronic literature databases for studies published between 01 January 2011 and 31 December 2022 yielded 26 studies, describing 13,570 PLWH in SSA, 61% of whom were receiving ART. Random effects models were used to calculate summary odds ratios (ORs) of the risk of diagnosis by ART status and corresponding 95% confidence intervals (95% CIs), where appropriate. ART use was associated with a small but imprecise increase in the odds of diabetes diagnosis (OR 1.07; 95% CI 0.71, 1.60) and an increase in the odds of hypertension diagnosis (OR 2.10, 95% CI 1.42, 3.09). We found minimal data on the association between ART use and screening, treatment, or control of NCDs. Despite a potentially higher NCD risk among PLWH and regional efforts to integrate NCD and HIV care, evidence to support effective care integration models is lacking.


Asunto(s)
Infecciones por VIH , Tamizaje Masivo , Enfermedades no Transmisibles , Humanos , África del Sur del Sahara/epidemiología , Fármacos Anti-VIH/uso terapéutico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/diagnóstico , Diabetes Mellitus/epidemiología , Diabetes Mellitus/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Hipertensión/diagnóstico , Enfermedades no Transmisibles/epidemiología , Enfermedades no Transmisibles/prevención & control
19.
ASAIO J ; 70(7): 625-632, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38300884

RESUMEN

There has been an increase in the use of extracorporeal membrane oxygenation (ECMO) to bridge critically ill patients to lung transplant (LTX). This study evaluates how ambulatory status on ECMO affected waitlist and post-LTX outcomes. The United Network of Organ Sharing (UNOS) database was queried for patients aged of greater than or equal to 18 years and between 2016 and 2021 to identify pre-LTX patients supported by ECMO. The patients were classified in venous-arterial (VA) ECMO and veno-venous (VV) ECMO cohorts and further classified as ambulatory (AMB) and non-AMB (nAMB). Each cohort was controlled against the non-ECMO patients. Univariate statistical tests, as well as Kaplan-Meier survival curves, were used for analysis. The 90 day waitlist survival was the highest among the non-ECMO group (96%), but both AMB VV and VA groups had superior survival compared to the nAMB group (85% vs. 75%, 78% vs. 65%, p < 0.01). After adjusting for the median lung allocation score (LAS) (88) in the VV ECMO group, the waitlist survival was superior in the AMB VV ECMO compared to those not on ECMO (86% vs. 78%, p > 0.01). The 1 year post-LTX survival between non-ECMO and AMB VV ECMO was comparable (88% vs. 88%, p = 0.66). Ambulating patients or use of physical therapy while on ECMO can help improve lung transplant outcomes.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Trasplante de Pulmón , Listas de Espera , Humanos , Oxigenación por Membrana Extracorpórea/métodos , Oxigenación por Membrana Extracorpórea/estadística & datos numéricos , Trasplante de Pulmón/métodos , Trasplante de Pulmón/estadística & datos numéricos , Masculino , Femenino , Persona de Mediana Edad , Listas de Espera/mortalidad , Adulto , Estudios Retrospectivos , Atención Ambulatoria/estadística & datos numéricos , Atención Ambulatoria/métodos
20.
ASAIO J ; 70(3): 239-240, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38411926
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