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BACKGROUND & AIMS: Although gastroparesis carries a considerable health care and patient burden, associated epidemiological data are limited. To provide new real-world evidence for gastroparesis, we estimated disease prevalence, and investigated patient demographics and disease etiology in a large US claims database. METHODS: This retrospective, cross-sectional analysis used de-identified, longitudinal patient-level enrollment and billing data for adults from the Optum Clinformatics Data Mart database, a large US national administrative health insurance claims database. Prevalence was age-, sex-, and geographical region-standardized using the 2018 US census. Descriptive analyses of demographic and clinical variables and underlying disease etiologies were performed. RESULTS: The overall standardized prevalence of gastroparesis was 267.7 (95% confidence interval [CI] 264.8-270.7) per 100,000 US adults, whereas prevalence of "definite" gastroparesis (individuals diagnosed within 3 months of gastric emptying scintigraphy testing with persistent symptoms for more than 3 months) was 21.5 (95% CI 20.6-22.4) per 100,000 persons. Patients with gastroparesis had an overall Charlson Comorbidity Index score of 4.2, indicating substantial comorbidity burden. The most frequently documented comorbidities were chronic pulmonary disease (46.4%), diabetes with chronic complication (37.3%), and peripheral vascular disease (30.4%). Patients most commonly had a diabetic etiology (57.4%; type 1, 5.7% and type 2, 51.7%), followed by postsurgical (15.0%), drug-induced (11.8%), and idiopathic (11.3%) etiologies. CONCLUSIONS: New evidence is provided regarding the prevalence, patient demographics, and etiology of gastroparesis in the US general population. Wider availability of reliable objective gastric emptying measures and further education of medical professionals in recognizing and diagnosing gastroparesis would benefit future studies and improve understanding of disease epidemiology.
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Gastroparesia/epidemiologia , Demandas Administrativas em Assistência à Saúde , Adolescente , Adulto , Fatores Etários , Idoso , Comorbidade , Estudos Transversais , Bases de Dados Factuais , Feminino , Esvaziamento Gástrico , Gastroparesia/diagnóstico , Gastroparesia/fisiopatologia , Gastroparesia/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
PURPOSE: Supplementing investigator-specified variables with large numbers of empirically identified features that collectively serve as 'proxies' for unspecified or unmeasured factors can often improve confounding control in studies utilizing administrative healthcare databases. Consequently, there has been a recent focus on the development of data-driven methods for high-dimensional proxy confounder adjustment in pharmacoepidemiologic research. In this paper, we survey current approaches and recent advancements for high-dimensional proxy confounder adjustment in healthcare database studies. METHODS: We discuss considerations underpinning three areas for high-dimensional proxy confounder adjustment: (1) feature generation-transforming raw data into covariates (or features) to be used for proxy adjustment; (2) covariate prioritization, selection, and adjustment; and (3) diagnostic assessment. We discuss challenges and avenues of future development within each area. RESULTS: There is a large literature on methods for high-dimensional confounder prioritization/selection, but relatively little has been written on best practices for feature generation and diagnostic assessment. Consequently, these areas have particular limitations and challenges. CONCLUSIONS: There is a growing body of evidence showing that machine-learning algorithms for high-dimensional proxy-confounder adjustment can supplement investigator-specified variables to improve confounding control compared to adjustment based on investigator-specified variables alone. However, more research is needed on best practices for feature generation and diagnostic assessment when applying methods for high-dimensional proxy confounder adjustment in pharmacoepidemiologic studies.
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Aprendizado de Máquina , Farmacoepidemiologia , Fatores de Confusão Epidemiológicos , Bases de Dados Factuais , Atenção à Saúde , HumanosRESUMO
OBJECTIVE: To generate real-world evidence for the epidemiology of gastroparesis in the UK, we evaluated the prevalence, incidence, patient characteristics and outcomes of gastroparesis in the Clinical Practice Research Datalink (CPRD) database. DESIGN: This was a retrospective, cross-sectional study. Prevalence and incidence of gastroparesis were evaluated in the CPRD database, with linkage to Hospital Episodes Statistics Admitted Patient Care and Office for National Statistics mortality data. Prevalence and incidence were age and sex standardised to mid-2017 UK population estimates. Descriptive analyses of demographics, aetiologies, pharmacological therapies and mortality were conducted. RESULTS: Standardised prevalence of gastroparesis, as documented in general practice records, was 13.8 (95% CI 12.6 to 15.1) per 100 000 persons in 2016, and standardised incidence of gastroparesis rose from 1.5 (95% CI 1.1 to 1.8) per 100 000 person-years in 2004 to 1.9 (95% CI 1.4 to 2.3) per 100 000 person-years in 2016. The most common disease aetiologies were idiopathic (39.4%) and diabetic gastroparesis (37.5%), with a similar distribution of type 1 and type 2 diabetes among the 90% who had type of diabetes documented. Patients with diabetic gastroparesis had a significantly higher risk of mortality than those with idiopathic gastroparesis after diagnosis (adjusted HR 1.9, 95% CI 1.2 to 3.0). Of those with gastroparesis, 31.6% were not offered any recognised pharmacological therapy after diagnosis. CONCLUSION: This is, to our knowledge, the first population-based study providing data on epidemiology and outcomes of gastroparesis in Europe. Further research is required to fully understand the factors influencing outcomes and survival of patients with gastroparesis.
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Gastroparesia/epidemiologia , Medicina Geral , Estudos Transversais , Feminino , Fármacos Gastrointestinais/uso terapêutico , Gastroparesia/tratamento farmacológico , Gastroparesia/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Reino Unido/epidemiologiaRESUMO
The activity-regulated gene Arc/Arg3.1 encodes a postsynaptic protein crucially involved in glutamatergic synaptic plasticity. Genetic mutations in Arc pathway and altered Arc expression in human frontal cortex have been associated with schizophrenia. Although Arc expression has been reported to vary with age, what mechanisms regulate Arc mRNA levels in frontal cortex during postnatal development remains unclear. Using quantitative mRNA analysis of mouse frontal cortical tissues, we mapped the developmental profiles of Arc expression and found that its mRNA levels are sharply amplified near the end of the second postnatal week, when mouse pups open their eyes for the first time after birth. Surprisingly, electrical stimulation of the frontal cortex before eye-opening is not sufficient to drive the amplification of Arc mRNA. Instead, this amplification needs both electrical stimulation and dopamine D1-type receptor (D1R) activation. Furthermore, visual stimuli-driven amplification of Arc mRNA is also dependent on D1R activation and dopamine neurons located in the ventral midbrain. These results indicate that dopamine is required to drive activity-dependent amplification of Arc mRNA in the developing postnatal frontal cortex and suggest that joint electrical and dopaminergic activation is essential to establish the normal expression pattern of a schizophrenia-associated gene during frontal cortical development.
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Complexo Relacionado com a AIDS/genética , Dopamina/metabolismo , Lobo Frontal/crescimento & desenvolvimento , Lobo Frontal/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , RNA Mensageiro/metabolismo , Complexo Relacionado com a AIDS/metabolismo , Adrenérgicos/farmacologia , Fatores Etários , Anfetamina/farmacologia , Animais , Animais Recém-Nascidos , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Benzazepinas/farmacologia , Dopaminérgicos/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Eletrochoque/métodos , Camundongos , Camundongos Endogâmicos C57BL , Análise em Microsséries , Oxidopamina/farmacologia , Receptores de Dopamina D1/metabolismo , Área Tegmentar Ventral/citologiaRESUMO
The brain encodes information about past experience in specific populations of neurons that communicate with one another by firing action potentials. Studies of experience-dependent neural plasticity have largely focused on individual synaptic changes in response to neuronal input. Indicative of the neuronal output transmitted to downstream neurons, persistent firing patterns are affected by prior experience in selective neuronal populations. However, little is known about the molecular and cellular mechanisms by which experience-related persistent firing patterns are regulated in specific neuronal populations. Using frontal cortical slices prepared from transgenic mice carrying a fluorescent reporter of Arc gene expression, this study investigates how behavioral experience and the activity-regulated Arc gene affect patterns of neuronal firing. We found that motor training increases Arc expression in subsets of excitatory neurons. Those neurons exhibit persistent firing in contrast to Arc-negative neurons from the same mice or neurons from the untrained mice. Furthermore, in mice carrying genetic deletion of Arc, the frontal cortical circuitry is still in place to initiate experience-dependent gene expression, but the level of persistent firing thereafter is diminished. Finally, our results showed that the emergence of persistent activity is associated with Arc-dependent changes in the function of NMDA-type glutamate receptors, rather than changes in AMPA-type receptors or membrane excitability. Our findings therefore reveal an Arc-dependent molecular pathway by which gene-experience interaction regulates the emergence of persistent firing patterns in specific neuronal populations.
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Proteínas do Citoesqueleto/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Córtex Pré-Frontal/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Bicuculina/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/fisiologia , Fenômenos Eletrofisiológicos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Antagonistas GABAérgicos/farmacologia , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Aprendizagem/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Destreza Motora/fisiologia , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Equilíbrio Postural/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Receptores de AMPA/fisiologiaRESUMO
The mesofrontal dopaminergic circuit, which connects the midbrain motivation center to the cortical executive center, is engaged in control of motivated behaviors. In addition, deficiencies in this circuit are associated with adolescent-onset psychiatric disorders in humans. Developmental studies suggest that the mesofrontal circuit exhibits a protracted maturation through adolescence. However, whether the structure and function of this circuit are modifiable by activity in dopaminergic neurons during adolescence remains unknown. Using optogenetic stimulation and in vivo two-photon imaging in adolescent mice, we found that phasic, but not tonic, dopamine neuron activity induces the formation of mesofrontal axonal boutons. In contrast, in adult mice, the effect of phasic activity diminishes. Furthermore, our results showed that dopaminergic and glutamatergic transmission regulate this axonal plasticity in adolescence and inhibition of dopamine D2-type receptors restores this plasticity in adulthood. Finally, we found that phasic activation of dopamine neurons also induces greater changes in mesofrontal circuit activity and psychomotor response in adolescent mice than in adult mice. Together, our findings demonstrate that the structure and function of the mesofrontal circuit are modifiable by phasic activity in dopaminergic neurons during adolescence and suggest that the greater plasticity in adolescence may facilitate activity-dependent strengthening of dopaminergic input and improvement in behavioral control.
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Neurônios Dopaminérgicos/fisiologia , Lobo Frontal/citologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Plasticidade Neuronal/fisiologia , Área Tegmentar Ventral/citologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/genética , Fatores Etários , Anfetamina/farmacologia , Animais , Animais Recém-Nascidos , Dextranos/farmacocinética , Dopaminérgicos/farmacologia , Fármacos Atuantes sobre Aminoácidos Excitatórios/farmacologia , Lobo Frontal/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Atividade Motora/efeitos dos fármacos , Atividade Motora/genética , Vias Neurais/fisiologia , Plasticidade Neuronal/genética , Desempenho Psicomotor/fisiologia , Rodaminas/farmacocinética , Tirosina 3-Mono-Oxigenase/genética , Área Tegmentar Ventral/metabolismoAssuntos
Gastroparesia , Bases de Dados Factuais , Hospitalização , Humanos , Prevalência , Estudos Retrospectivos , Estados UnidosRESUMO
This paper presents a micromachined thermal convective accelerometer with low power and high reliability. This accelerometer comprises a heater and two thermistors. The central heater elevates the temperature of the chip above ambient levels while the symmetrically arranged thermistors monitor the temperature differentials induced by acceleration. The heater and thermistors are fabricated on a glass substrate using a standard micro-electromechanical systems (MEMS) process flow, and the fabricated sensor is installed on a rotation platform and a shaking table experimental setup to perform the experiment. The results indicate that the sensor has the capability to measure accelerations surpassing 80 m/s2, with an approximate linear sensitivity of 110.69 mV/g. This proposed thermal convective accelerometer offers promising potential for various applications requiring precise acceleration measurements in environments where low power consumption and high reliability are paramount.
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INTRODUCTION: Ascending aorta or hemi-arch replacement is a frequently used treatment for patients with acute type A thoracic aortic dissection, particularly those who are elderly or have multiple comorbidities. However, in cases where there are secondary entry tears in the aortic arch or descending aorta, this procedure may not fully resolve the issue. The true lumen may remain compressed due to perfusion of the false lumen and usually require reoperation. METHODS: Between January 2019 and July 2022, 18 patients underwent endovascular total aortic arch repair and fenestration technique without requiring median re-sternotomy. Aortic stent grafts were implanted via the femoral approach, utilizing prosthetic vessels as an appropriate proximal landing zone for aortic stent graft deployment. Based on the debranching conditions of the arch in previous surgery, single, double or triple in situ fenestrations (ISFs) were performed, respectively. RESULTS: All 18 cases were technically successful, with a median follow-up period of 20 months (range: 18-31 months). All patients had a favourable postoperative course, with no deaths within 30 days or during their hospital stay. There were no instances of disabling stroke, paraplegia, endo-leak, stent graft migration or stent graft-induced new entry. In addition, all patients exhibited complete thrombosis of the false lumen at the level of the aortic arch. CONCLUSION: Our preliminary experience suggests that endovascular total arch repair combined with ISF technique is a viable, effective and safe option for treatment. Our mid-term results have been promising, but we acknowledge the need for further evaluation to assess long-term outcomes and durability.
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Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Idoso , Prótese Vascular , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/etiologia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos , Resultado do Tratamento , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Stents , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Estudos Retrospectivos , Desenho de PróteseRESUMO
INTRODUCTION: This prospective, longitudinal, community-based study, EpidemiologiCal POpulatioN STudy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Lake CounTy, Illinois (CONTACT), investigated coronavirus disease 2019 (COVID-19) immunity, occupational risks related to SARS-CoV-2 exposure, and long-term immunoglobulin G (IgG) seroconversion kinetics. METHODS: At baseline and follow up (3, 6, and 9 months), non-hospitalized adult participants provided nasal and blood serum specimens for molecular [reverse transcription polymerase chain reaction (RT-PCR)] and serological (IgG) testing (4 November 2020-30 October 2021). RESULTS: At baseline, 6.4% (65/1008) had evidence of current/prior SARS-CoV-2 infection. At 3, 6, and 9 months, positive PCR tests were obtained from 0.4% (3/781), 0.4% (3/733), and 0% (0/673) of participants, respectively. Positive IgG occurred at baseline and 3, 6, and 9 months in 4.5% (45/1008), 6.0% (48/799), 5.4% (39/733), and 2.8% (19/673) of participants, respectively. Of participants positive for IgG at baseline, 28 had a negative IgG test at a follow-up visit; of those 28, 21 had their first negative IgG test within 6 months. Participants were more likely to retain positive IgG if they were 18-29 years of age, were male, or had medium-high/high-risk occupations. A high vaccination rate (70% received ≥ 1 dose by 9 months) was observed. Influence of occupational status or characteristics on transmission and IgG, and COVID-19 vaccination trends, are shown. CONCLUSIONS: This study expands on prior studies assessing COVID-19 immunity and IgG seroconversion by including both RT-PCR and serologic testing and longitudinal follow-up of study participants. We observed decreased infection rates over the 9 month follow-up period as well as a decline in IgG persistency after 6 months. The findings from this community-based study regarding vaccinate rates, infection rates by PCR, and IgG persistency over time can help improve our understanding of COVID-19 immunity, occupational risks related to SARS-CoV-2 exposure, and the kinetics of long-term IgG seroconversion, which is important to help guide local and national mitigation strategies. CLINICAL TRIAL REGISTRATION: NCT04611230.
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Psoriasis is a chronic skin disease characterized by abnormal proliferation and inflammation of epidermal keratinocytes. Fibroblast growth factor 12 (FGF12) is implicated in the regulation of diverse cellular signals; however, its precise mechanism in psoriasis requires further investigation. In this study, high expression of FGF12 is observed in the epidermis of skin lesion in psoriasis patients and imiquimod (IMQ)-induced psoriasis like-dermatitis. Moreover, specific loss of FGF12 in keratinocytes in IMQ-induced psoriasis model alleviates psoriasis-like symptoms and reduces proliferation. In vitro RNA sequencing demonstrates that knockdown of FGF12 effectively arrests the cell cycle, inhibits cell proliferation, and predominantly regulates the p53 signaling pathway. Mechanistically, FGF12 is selectively bound to the RING domain of MDM2, thus partially inhibiting the binding of ß-Trcp to MDM2. This interaction inhibits ß-Trcp-induced-K48 ubiquitination degradation of MDM2, thereby suppressing the activity of the p53 signaling pathway, which results in excessive cell proliferation. Last, the alleviatory effect of FGF12 deficiency on psoriasis progression is reversed by p53 knockdown. In summary, these findings provide valuable insights into the mechanisms by which FGF12 suppresses p53 signaling in keratinocytes, exacerbating the development of psoriasis. This positive regulatory loop highlights the potential of FGF12 as a therapeutic target to manage psoriasis.
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INTRODUCTION: To evaluate factors associated with severe coronavirus disease 2019 (COVID-19) among patients with rheumatoid arthritis (RA) in the US. METHODS: Adults with RA who had a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, based on molecular or antigen test or clinical diagnosis, were identified from the Optum® COVID-19 Electronic Health Record dataset (March 1, 2020-April 28, 2021). The primary outcome was the occurrence of severe COVID-19 (hospitalization or death) within 30 days from SARS-CoV-2 infection. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models to assess the association between severe COVID-19 and patient characteristics, including demographics, baseline comorbidities, and recent RA treatments. RESULTS: During the study period, 6769 SARS-CoV-2 infections were identified in patients with RA, among whom 1460 (22%) developed severe COVID-19. Multivariable logistic regression analysis showed that being older, male, and non-White and having diabetes and cardiovascular conditions are associated with greater odds of severe COVID-19. In addition, compared with no use, the adjusted odds of severe COVID-19 were lower with recent use of tumor necrosis factor inhibitors (aOR 0.60, 95% CI 0.41-0.86) and higher with recent use of corticosteroids (aOR 1.38, 95% CI 1.13-1.69) or rituximab (aOR 2.87, 95% CI 1.60-5.14), respectively. CONCLUSION: Nearly one in five patients with RA developed severe COVID-19 disease within 30 days after SARS-CoV-2 infection. In patients with RA, recent use of corticosteroids and rituximab were two factors associated with a greater risk of severe COVID-19 in addition to the risk factors among demographics and comorbidities previously identified in the general population.
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Artrite Reumatoide , COVID-19 , Adulto , Humanos , Masculino , Estados Unidos/epidemiologia , SARS-CoV-2 , Estudos de Coortes , Rituximab , Registros Eletrônicos de Saúde , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Corticosteroides/uso terapêuticoRESUMO
In this paper, the effect of wind-induced vibration on measurement range of microcantilever anemometer is investigated for the first time. The microcantilever anemometer is composed of a flexible substrate and a piezoresistor. The wind speed can be detected through the airflow-induced deformation in the flexible substrate. Previous work indicated that the flexible substrate vibrates violently once the wind speed exceeds a critical value, resulting in severe output jitter. This wind-induced vibration limits the measurement range of the anemometer, and the relationship between the anemometer measurement range and its structural parameters has not been explored systematically. Therefore, this paper aims to reveal this relationship theoretically and experimentally, demonstrating that a shorter and thicker cantilever with larger stiffness can effectively suppress the wind-induced vibration, leading to the critical speed rising. By eliminating the wind-induced vibration, the measurement range of the microcantilever anemometer can be increased by up to 697%. These results presented in this paper can pave the way for the design and fabrication of wide-range mechanical anemometers.
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Background: Nosocomial infection (NI) prolongs hospital stay and heightens mortality among patients who underwent cardiac surgery. We constructed a retrospective study to explore the prevalence of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (SA/MRSA) nasal colonization, as well as the effects of SA/MRSA decolonization bundle measures on SA/MRSA-related infection among Chinese cardiac patients. Methods: After reviewing the medical records, we divided cardiovascular surgery patients treated at our central campus into two groups: the baseline group (treated between January 2012 and December 2013) and the intervention group (treated between May 2014 and December 2020). Intervention measures consisted of preoperative nasal screening and targeted decolonization bundle therapy. The medical records of patients at our southern campus (treated between January 2017 and December 2020) were collected as an additional control group, since we did not implement SA intervention measures at this location. The incidences of SA/MRSA-related NI were then compared between the groups. Results: There were 794 patients in the baseline group and 2,826 in the intervention group. A total of 131 (4.6%) patients had SA nasal colonization, and among them, 33 patients (1.2%) were MRSA colonized. SA/MRSA was cleared in approximately 95% of the carriers. The total level of SA-related infection was significantly lower in the intervention group compared to the baseline group [0.354% vs. 1.133%, respectively; P=0.021; risk ratio (RR): 0.312; 95% confidence interval (CI): 0.127-0.766]. The incidence of MRSA-related infection followed the same trend (0.212% vs. 0.756%, respectively; P=0.030; RR: 0.281; 95% CI: 0.091-0.860). When compared to the southern campus, SA intervention measures at the central campus resulted in a significant reduction in total SA-related infection (1.132% vs. 0.284%, respectively; P=0.035; RR: 0.251; 95% CI: 0.077-0.820). Conclusions: The prevalence of SA/MRSA colonization is relatively low among Chinese patients who received cardiovascular surgery. Targeted decolonization bundle therapy was associated with cleared colonization and reduced incidence of SA/MRSA-related infection.
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An important step of somatic variant calling algorithms for deep sequencing data is quantifying the errors. For targeted sequencing in which hotspot mutations are of interest, site-specific error estimation allows more accurate calling. The site-specific error rates are often estimated from a panel of normal samples, which has limited size and is subject to sampling bias and variance. We propose a novel statistical validation method for single-nucleotide variation (SNV) calling based on historical data. The validation method extracts the high-quality reads from the Binary Alignment/Map (BAM) files, finds the negative samples in the data, and builds a statistical model to call individual samples. It is particularly useful in detecting low-frequency variants that may be missed by traditional panel of normal-based SNV methods. The proposed method makes it possible to launch a simple and parallel validation pipeline for SNV calling and improve the detection limit.
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Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias , Algoritmos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Nucleotídeos , Polimorfismo de Nucleotídeo Único/genética , Estudos RetrospectivosRESUMO
INTRODUCTION: There are concerns that patients in an immunocompromised state may be at risk for increased coronavirus disease 2019 (COVID-19) severity. The aim of this study was to describe the characteristics of patients with COVID-19 and immune-mediated inflammatory diseases (IMIDs) or malignancies and evaluate their risk of developing severe COVID-19. METHODS: Cases of COVID-19 (ICD-10 code U07.1 or U07.2, or positive polymerase chain reaction or antigen test) among patients with IMIDs or malignancies were identified in the US-based Optum® Electronic Health Records database between 1 February 2020 and 3 March 2021. Age- and sex-standardized risks of severe COVID-19 were calculated by condition of interest. The risks were further adjusted by multiple covariates, and 95% confidence intervals were estimated. RESULTS: A total of 499,772 patients with COVID-19 were identified (mean [SD] age, 46.9 [20.7] years; 57.0% female). Patients with hematologic cancers (adjusted risk ratio [aRR] 2.0, 1.8-2.1), solid tumors (aRR 1.1, 1.1-1.1), or rheumatoid arthritis (aRR 1.2, 1.1-1.3) had a significantly higher risk of severe COVID-19 compared to the general population of patients with COVID-19. Patients with systemic lupus erythematosus (aRR 1.1, 0.9-1.2), psoriasis (aRR 1.0, 0.7-1.2), ulcerative colitis (aRR 0.9, 0.8-1.1), Crohn's disease (aRR 0.9, 0.7-1.0), or ankylosing spondylitis (aRR 0.8, 0.5-1.0) showed a comparable risk of severe COVID-19. Patients with atopic dermatitis (aRR 0.8, 0.7-0.9) or psoriatic arthritis (aRR 0.8, 0.6-1.0) showed a lower risk of severe COVID-19. CONCLUSIONS: The risk of developing severe COVID-19 varied between the studied IMIDs and malignancies. Patients with hematologic cancers, solid tumors, or rheumatoid arthritis had significantly increased risk for severe COVID-19 compared to the general population. These findings highlight the need to protect and monitor immunocompromised patients such as those with IMIDs or malignancies as part of the strategy to control the pandemic worldwide.
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Artrite Reumatoide , COVID-19 , Neoplasias Hematológicas , Neoplasias , Humanos , Feminino , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Masculino , COVID-19/epidemiologia , Estudos Retrospectivos , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Neoplasias/epidemiologia , Neoplasias Hematológicas/epidemiologiaRESUMO
Urokinase is widely used in the dissolution of an acute pulmonary embolism due to its high biocatalytic effect. However, how to precisely regulate its dose, avoid the side effects of hemolysis or ineffective thrombolysis caused by too high or too low a dose, and seize the golden time of acute pulmonary embolism are the key factors for its clinical promotion. Therefore, based on the precise design of a molecular structure, an ultrasonic-responsive nanoliposome capsule was prepared in this paper. Singlet oxygen is continuously generated under the interaction of the ultrasonic cavitation effect and the sonosensitizer protoporphyrin, and the generated singlet oxygen will break the thiol acetone bond between the hydrophilic head and the hydrophobic tail of the liposome, and the lipid The body structure disintegrates rapidly, and the urokinase encapsulated inside is rapidly released, down-regulating the expression of fibrinogen in the body, and exerting a thrombolytic function. The in vitro and in vivo results show that the smart urokinase nanoliposomes prepared by us have sensitive and responsive cytocompatibility to ultrasound and good in vivo thrombolytic properties for acute pulmonary embolism, which provides a new strategy for clinical acute pulmonary embolism thrombolysis.
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INTRODUCTION: EpidemiologiCal POpulatioN STudy of SARS-CoV-2 in Lake CounTy, Illinois (CONTACT) is an observational, epidemiological study with a 9-month longitudinal follow-up of nonhospitalized persons aged 18 years or older currently living or employed in Lake County, IL. We describe the study design and report baseline characteristics of the study participants, including the proportion of participants with acute or previous SARS-CoV-2 infection at enrollment. METHODS: At enrollment and subsequent timepoints, participants recruited through digital and paper-based advertising campaigns reported their occupational and school-based exposure, risk factors, and behaviors, and provided nasal and serum specimens. Stratified enrichment was used to enhance enrollment into medium- and higher-risk groups within four occupational risk groups for SARS-CoV-2 infection. RT-PCR and serologic (IgG) testing were conducted to detect acute or previous SARS-CoV-2 infection in participants, respectively. RESULTS: Between November 2020 and January 2021, 1008 participants (female 70.7%, mean age ± SD 51 ± 13.8 years) completed the questionnaire and diagnostic testing. Among participants, 41.8% (n = 421) were considered low risk, 24.6% (n = 248) were medium-to-low risk, 22.3% (n = 225) were medium-to-high risk, and 11.3% (n = 114) were high risk. Of 56 (5.6%) participants with evidence of acute or previous SARS-CoV-2 infection at baseline, 11 (19.6%) were RT-PCR-positive, 36 (64.3%) were IgG-seropositive, and 9 (16.1%) were positive by both assays. Participants who were adherent vs nonadherent to social distancing measures (odds ratio [95% CI] 0.8 [0.4-1.8]) were less likely, while those in higher vs lower occupational risk groups (2.0 [1.0-4.4]) were more likely to have evidence for acute or previous SARS-CoV-2 infection. CONCLUSION: In fall/winter 2020/21, 5.6% of adults in a Lake County convenience sample had evidence for acute or previous SARS-CoV-2 infection at baseline. Nonadherence to social distancing measures and high-risk professions were associated with SARS-CoV-2 infection. The study is ongoing and future analyses will assess infection status over time. CLINICAL TRIAL REGISTRATION: NCT04611230.
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As the scientific research community along with healthcare professionals and decision makers around the world fight tirelessly against the coronavirus disease 2019 (COVID-19) pandemic, the need for comparative effectiveness research (CER) on preventive and therapeutic interventions for COVID-19 is immense. Randomized controlled trials markedly under-represent the frail and complex patients seen in routine care, and they do not typically have data on long-term treatment effects. The increasing availability of electronic health records (EHRs) for clinical research offers the opportunity to generate timely real-world evidence reflective of routine care for optimal management of COVID-19. However, there are many potential threats to the validity of CER based on EHR data that are not originally generated for research purposes. To ensure unbiased and robust results, we need high-quality healthcare databases, rigorous study designs, and proper implementation of appropriate statistical methods. We aimed to describe opportunities and challenges in EHR-based CER for COVID-19-related questions and to introduce best practices in pharmacoepidemiology to minimize potential biases. We structured our discussion into the following topics: (1) study population identification based on exposure status; (2) ascertainment of outcomes; (3) common biases and potential solutions; and (iv) data operational challenges specific to COVID-19 CER using EHRs. We provide structured guidance for the proper conduct and appraisal of drug and vaccine effectiveness and safety research using EHR data for the pandemic. This paper is endorsed by the International Society for Pharmacoepidemiology (ISPE).
Assuntos
COVID-19 , Pesquisa Comparativa da Efetividade , Humanos , Pesquisa Comparativa da Efetividade/métodos , Registros Eletrônicos de Saúde , Farmacoepidemiologia , Pandemias/prevenção & controleRESUMO
ABSTRACT: In precision oncology, immune check point blockade therapy has quickly emerged as novel strategy by its efficacy, where programmed death ligand 1 (PD-L1) expression is used as a clinically validated predictive biomarker of response for the therapy. Automating pathological image analysis and accelerating pathology evaluation is becoming an unmet need. Artificial Intelligence and deep learning tools in digital pathology have been studied in order to evaluate PD-L1 expression in PD-L1 immunohistochemistry image. We proposed a Dual-scale Categorization (DSC)-based deep learning method that employed 2 VGG16 neural networks, 1 network for 1 scale, to critically evaluate PD-L1 expression. The DSC-based deep learning method was tested in a cohort of 110 patients diagnosed as non-small cell lung cancer. This method showed a concordance of 88% with pathologist, which was higher than concordance of 83% of 1-scale categorization-based method. Our results show that the DSCbased method can empower the deep learning application in digital pathology and facilitate computer-aided diagnosis.