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1.
J Am Coll Cardiol ; 78(20): 1954-1964, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34763772

RESUMO

BACKGROUND: Raised low-density lipoprotein cholesterol (LDL-C) in young adulthood (aged 18-39 years) is associated with atherosclerotic cardiovascular disease (ASCVD) later in life. Most young adults with elevated LDL-C do not currently receive lipid-lowering treatment. OBJECTIVES: This study aimed to estimate the prevalence of elevated LDL-C in ASCVD-free U.S. young adults and the cost-effectiveness of lipid-lowering strategies for raised LDL-C in young adulthood compared with standard care. METHODS: The prevalence of raised LDL-C was examined in the U.S. National Health and Nutrition Examination Survey. The CVD Policy Model projected lifetime quality-adjusted life years (QALYs), health care costs, and incremental cost-effectiveness ratios (ICERs) for lipid-lowering strategies. Standard care was statin treatment for adults aged ≥40 years based on LDL-C, ASCVD risk, or diabetes plus young adults with LDL-C ≥190 mg/dL. Lipid lowering incremental to standard care with moderate-intensity statins or intensive lifestyle interventions was simulated starting when young adult LDL-C was either ≥160 mg/dL or ≥130 mg/dL. RESULTS: Approximately 27% of ASCVD-free young adults have LDL-C of ≥130 mg/dL, and 9% have LDL-C of ≥160 mg/dL. The model projected that young adult lipid lowering with statins or lifestyle interventions would prevent lifetime ASCVD events and increase QALYs compared with standard care. ICERs were US$31,000/QALY for statins in young adult men with LDL-C of ≥130 mg/dL and US$106,000/QALY for statins in young adult women with LDL-C of ≥130 mg/dL. Intensive lifestyle intervention was more costly and less effective than statin therapy. CONCLUSIONS: Statin treatment for LDL-C of ≥130 mg/dL is highly cost-effective in young adult men and intermediately cost-effective in young adult women.

2.
Cancer Med ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34796687

RESUMO

PURPOSE: To evaluate the impact of the log odds of positive lymph nodes (LODDS) on cancer-specific survival (CSS) in colon mucinous adenocarcinoma (MAC) patients, compared with pN stage and the lymph nodes ratio (LNR). METHODS: A total of 10,182 colon MAC patients from the Surveillance, Epidemiology, and End Results database were divided into the training group. The external validation group included 153 patients from Fujian Medical University Union Hospital. The Cox regression method was used to identify prognostic risk factors. Nomograms were evaluated by Harrell's concordance index (C-index) and calibration curves. Recursive partitioning analysis (RPA) was used to develop a novel staging system. RESULTS: Time-dependent receiver operating characteristic curves (ROC) to predict CSS showed the areas under the ROC curve of LODDS were always higher than pN stage and LNR. LNR and LODDS classifications can well distinguish the prognosis of patients with the same pN stage. Cox analyses indicated that age, tumor size, pT stage, pN stage, LNR, and LODDS were independent predictors of CSS (p < 0.05). Based on three lymph nodes classifications, we constructed three prognostic nomograms models for CSS. The C-index of the pN, LNR, and LODDS classification nomograms were 0.746 (95% confidence interval [95% CI]: 0.736-0.756), 0.750 (95% CI: 0.740-0.760), and 0.758 (95% CI: 0.748-0.768), respectively. In external validation, we observed the C-index of LODDS classification nomograms was 0.787 (95% CI: 0.648-0.926). RPA stage, including four stages, was constructed successfully based on pT stage and LNR or LODDS, respectively. The 3-, 5-, and 8-year areas under the ROC curve of LNR-RPA stage and LODDS-RPA stage were superior to tumor-node-metastasis stage. CONCLUSION: LODDS to be a better prognostic factor of CSS for colon MAC patients than pN stage and LNR. A nomogram and RPA stage base on LODDS can provide accurate information for personalized cancer treatment.

3.
Curr Med Sci ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34705216

RESUMO

OBJECTIVE: Keshan disease (KD) is a mitochondrial cardiomyopathy. The present study explored the roles of peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), the key regulator of mitochondrial structure and function, and its coactivators in myocardial injury in chronic KD. Furthermore, the usefulness of these molecules in the diagnosis of chronic KD was assessed. METHODS: In the present case-control study, 43 patients with chronic KD and 30 healthy individuals living in KD endemic areas were included. The myocardial injury indicators and mRNA expression levels of PGC-1α, nuclear respiratory factor 1 (NRF1), PPARα, and estrogen-related receptor alpha (ERRα) in peripheral blood were examined. RESULTS: It was found that the levels of atrial natriuretic peptide, creatine kinase, and lactate dehydrogenase (LDH) were higher in patients with chronic KD, when compared to controls, while the level of bradykinin was lower. Furthermore, the PGC-1α, NRF1 and PPARα mRNA levels were higher in patients with KD. The area under the receiver operating characteristic curve and the optimal diagnostic threshold of LDH was 0.937 and 304.0 U/L, respectively. It is noteworthy that the area under the combined receiver operating characteristic curve was larger, when compared to that for LDH detection alone (Z=2.055, P=0.0399). The area under the curve for the "LDH+PPARα" combination was 0.984, with 96.7% sensitivity and 93.0% specificity. CONCLUSION: The combined detection of LDH and the expression of PPARα can be performed to diagnose the chronic KD.

4.
Front Cell Dev Biol ; 9: 607782, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485268

RESUMO

Background: To identify the hub genes associated with chemoradiotherapy resistance in rectal cancer and explore the potential mechanism. Methods: Weighted gene co-expression network analysis (WGCNA) was performed to identify the gene modules correlated with the chemoradiotherapy resistance of rectal cancer. Results: The mRNA expression of 31 rectal cancer patients receiving preoperative chemoradiotherapy was described in our previous study. Through WGCNA, we demonstrated that the chemoradiotherapy resistance modules were enriched for translation, DNA replication, and the androgen receptor signaling pathway. Additionally, we identified and validated UTP6 as a new effective predictor for chemoradiotherapy sensitivity and a prognostic factor for the survival of colorectal cancer patients using our data and the GSE35452 dataset. Low UTP6 expression was correlated with significantly worse disease-free survival (DFS), overall survival (OS), and event- and relapse-free survival both in our data and the R2 Platform. Moreover, we verified the UTP6 expression in 125 locally advanced rectal cancer (LARC) patients samples by immunohistochemical analysis. The results demonstrated that low UTP6 expression was associated with worse DFS and OS by Kaplan-Meier and COX regression model analyses. Gene set enrichment and co-expression analyses showed that the mechanism of the UTP6-mediated chemoradiotherapy resistance may involve the regulation of FOXK2 expression by transcription factor pathways. Conclusion: Low expression of the UTP6 was found to be associated with chemoradiotherapy resistance and the prognosis of colorectal cancer possibly via regulating FOXK2 expression by transcription factor pathways.

5.
JAMA Cardiol ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550307

RESUMO

Importance: Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease (CVD). Most observational studies on the association between LDL-C and CVD have focused on LDL-C level at a single time point (usually in middle or older age), and few studies have characterized long-term exposures to LDL-C and their role in CVD risk. Objective: To evaluate the associations of cumulative exposure to LDL-C, time-weighted average (TWA) LDL-C, and the LDL-C slope change during young adulthood and middle age with incident CVD later in life. Design, Setting, and Participants: This cohort study analyzed pooled data from 4 prospective cohort studies in the US (Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Framingham Heart Study Offspring Cohort, and Multi-Ethnic Study of Atherosclerosis). Participants were included if they had 2 or more LDL-C measures that were at least 2 years apart between ages 18 and 60 years, with at least 1 of the LDL-C measures occurring during middle age at 40 to 60 years. Data from 1971 to 2017 were collected and analyzed from September 25, 2020, to January 10, 2021. Exposures: Cumulative exposure to LDL-C, TWA LDL-C, and LDL-C slope from age 18 to 60 years. Main Outcomes and Measures: Incident coronary heart disease (CHD), ischemic stroke, and heart failure (HF). Results: A total of 18 288 participants were included in this study. These participants had a mean (SD) age of 56.4 (3.7) years and consisted of 10 309 women (56.4%). During a median follow-up of 16 years, 1165 CHD, 599 ischemic stroke, and 1145 HF events occurred. In multivariable Cox proportional hazards regression models that adjusted for the most recent LDL-C level measured during middle age and for other CVD risk factors, the hazard ratios for CHD were as follows: 1.57 (95% CI, 1.10-2.23; P for trend = .01) for cumulative LDL-C level, 1.69 (95% CI, 1.23-2.31; P for trend <.001) for TWA LDL-C level, and 0.88 (95% CI, 0.69-1.12; P for trend = .28) for LDL-C slope. No association was found between any of the LDL-C variables and ischemic stroke or HF. Conclusions and Relevance: This cohort study showed that cumulative LDL-C and TWA LDL-C during young adulthood and middle age were associated with the risk of incident CHD, independent of midlife LDL-C level. These findings suggest that past levels of LDL-C may inform strategies for primary prevention of CHD and that maintaining optimal LDL-C levels at an earlier age may reduce the lifetime risk of developing atherosclerotic CVD.

6.
Vet Microbiol ; 261: 109216, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34481271

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is a serious infectious disease in the swine industry, which causes severe economic losses to current swine production worldwide. There are no effective antiviral strategies for preventing this disease. Previous studies showed that microRNAs (miRNAs) play important role in virus-host interactions. In this study, we demonstrated that the expression level of ssc-miR-124a was significantly downregulated during both high and low pathogenic PRRSV infection. Overexpression of ssc-miR-124a markedly inhibits PRRSV replication in PAMs. Luciferase reporter experiments and RISC immunoprecipitation assay were used to identify the ssc-miR-124a could directly target the 3'UTR of pig CD163 mRNA in a sequence-specific manner and that CD163 mRNA and protein levels were reduced in PAMs overexpressing ssc-miR-124a. These data not only provide new insights into virus-host interactions during PRRSV infection, but also suggest potential new antiviral strategies against PRRSV infection in the future.


Assuntos
Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Regulação da Expressão Gênica/imunologia , Interações entre Hospedeiro e Microrganismos/genética , Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/virologia , Receptores de Superfície Celular/genética , Animais , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Suínos
7.
Artigo em Inglês | MEDLINE | ID: mdl-34302728

RESUMO

CONTEXT: The independent contribution of young adult exposure to overweight and obesity to later life incident diabetes is not well studied. OBJECTIVE: To assess the associations of exposures to elevated body mass index (BMI) and waist circumference (WC) in young adulthood (ages 18 to 39 years) with incident diabetes later in life (≥40 years). DESIGN: Pooled data from six US prospective cohorts (ARIC, CARDIA, CHS, Framingham Offspring, Health ABC, MESA). SETTING: Population-based cohort studies. PARTICIPANTS: 30,780 participants (56.1% female, 69.8% non-Hispanic White) without a diagnosis of diabetes by age 40. INTERVENTIONS: We imputed BMI and WC trajectories from age 18 for every participant and estimated time-weighted average exposures to BMI or WC during young adulthood and later life. MAIN OUTCOME MEASURE(S): Incident diabetes defined as fasting glucose ≥126 mg/dL, non-fasting glucose ≥200 mg/dL, or use of diabetes medications. RESULTS: During a 9-year median follow-up, 4,323 participants developed incident diabetes. Young adult BMI and WC were associated with later life incident diabetes after controlling for later life exposures (hazard ratios [HR] 1.99 for BMI ≥30 kg/m 2 and 2.13 for WC >88cm [women]/>102cm [men] compared to normal ranges). Young adult homeostatic model of insulin resistance (HOMA-IR) mediated 49% and 44% of the association between BMI and WC with later life incident diabetes. HDL and triglycerides mediated a smaller proportion of these associations. CONCLUSIONS: Elevated BMI and WC during young adulthood were independently associated with later life incident diabetes. Insulin resistance appears to be a key mediator.

8.
Bosn J Basic Med Sci ; 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34247568

RESUMO

While the prognosis of patients with partial SRCC (PSRCC) has been rarely reported, colorectal signet-ring cell carcinoma (SRCC) has been associated with poor prognosis. The aim of this study was to analyze the prognosis of patients with different SRCC composition and establish a prediction model. A total of 91 patients with SRC component were included in the study. These patients were divided into two groups: SRCC group (SRC composition > 50%; n=41) and partial SRCC (PSRCC) group (SRC composition ≤ 50%; n=50). COX regression model was used to identify independent prognostic factors for overall survival (OS). A predictive nomogram was established and compared with the 7th AJCC staging system. After a median follow-up of 16 months, no significant difference in OS was observed in either group. Preoperative carcinoembryonic antigen (CEA) level, pN stage, M stage, preoperative ileus, and adjuvant chemotherapy were independent prognostic risk factors for OS (p<0.05). A nomogram for predicting the overall survival of colorectal SRCC was established with a C-index of 0.800, and it showed better performance than that of the 7th AJCC staging system (p<0.001). In summary, the ratio of SRC component was not an independent prognostic factor of the OS. Those patients with less than 50% of SRC component should be given the same clinical attention. A predictive nomogram for survival based on five independent prognostic factors was developed and showed better performance than the 7th AJCC staging system. This resulted to be helpful for individualized prognosis prediction and risk assessment.

10.
J Surg Oncol ; 124(7): 1098-1105, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34291822

RESUMO

BACKGROUND: The well-differentiated rectal neuroendocrine tumors (RNETs) can also have lymph node metastasis (LNM). Large multicenter data were reviewed to explore the risk factors for LNM in RNETs. Further, we developed a model to predict the risk of LNM in RNETs. METHODS: In total, 223 patients with RNETs from the Fujian Medical University Union Hospital, the First Affiliated Hospital of Fujian Medical University, and the First Affiliated Hospital of Xiamen University were retrospectively enrolled. Logistic regression analysis was performed to study the factors affecting LNM, and recursive partitioning analysis (RPA) was performed to stratify the risk of LNM. RESULTS: Among the 223 patients diagnosed with RNETs, the incidence of LNM was 10.8%. Univariate and multivariate regression analyses revealed that tumor size, World Health Organization (WHO) grade, and depth of tumor invasion were independent risk factors for LNM (p < 0.05). The area under the curve was 0.948 (95% confidence interval: 0.890-1.000). Furthermore, the incidence of LNM in patients divided into low- and high-risk groups according to RPA was 1.1% and 56.4%, respectively. CONCLUSION: Compared with tumor size, the depth of tumor invasion and WHO grade are more important factors in predicting LNM. Then, we developed a model based on RPA to predict the risk of LNM in RNETs and identify patients who are suitable for local resection.


Assuntos
Metástase Linfática , Tumores Neuroendócrinos/mortalidade , Neoplasias Retais/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Invasividade Neoplásica , Tumores Neuroendócrinos/patologia , Neoplasias Retais/mortalidade , Estudos Retrospectivos , Fatores de Risco
11.
Nanomicro Lett ; 13(1): 141, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34138357

RESUMO

The highly immunosuppressive microenvironment after surgery has a crucial impact on the recurrence and metastasis in breast cancer patients. Programmable delivery of immunotherapy-involving combinations through a single drug delivery system is highly promising, yet greatly challenging, to reverse postoperative immunosuppression. Here, an injectable hierarchical gel matrix, composed of dual lipid gel (DLG) layers with different soybean phosphatidylcholine/glycerol dioleate mass ratios, was developed to achieve the time-programmed sequential delivery of combined cancer immunotherapy. The outer layer of the DLG matrix was thermally responsive and loaded with sorafenib-adsorbed graphene oxide (GO) nanoparticles. GO under manually controlled near-infrared irradiation generated mild heat and provoked the release of sorafenib first to reeducate tumor-associated macrophages (TAMs) and promote an immunogenic tumor microenvironment. The inner layer, loaded with anti-CD47 antibody (aCD47), could maintain the gel state for a much longer time, enabling the sustained release of aCD47 afterward to block the CD47-signal regulatory protein α (SIRPα) pathway for a long-term antitumor effect. In vivo studies on 4T1 tumor-bearing mouse model demonstrated that the DLG-based strategy efficiently prevented tumor recurrence and metastasis by locally reversing the immunosuppression and synergistically blocking the CD47-dependent immune escape, thereby boosting the systemic immune responses.

13.
Int J Mol Med ; 48(1)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34080654

RESUMO

Skeletal muscle atrophy is a common feature of patients suffering with chronic infection and other systemic diseases, including acquired immunodeficiency syndrome, chronic kidney disease and cancer. Therefore, understanding the molecular basis of muscle loss is of importance. The majority of members of the forkhead box O (FoxO) family can induce skeletal muscle atrophy; however, the effect of FoxO6 on skeletal muscle is not completely understood. The present study investigated the role of FoxO6 in vitro and in vivo. Compared with the small interfering RNA (si)­negative control (NC) group, C2C12 cell proliferation (Cell Counting Kit­8 assay), myotube differentiation and myotube production were significantly decreased by FoxO6 knockdown, which was different from the known functions of other FoxO members. The immunofluorescence assay results demonstrated that si­FoxO6 clearly downregulated the expression levels of myosin heavy chain (MyHC) in C2C12 myotubes compared with si­NC. The western blotting results indicated that compared with the si­NC group, FoxO6 knockdown induced C2C12 myotube atrophy by notably downregulating myoblast determination protein 1 (MyoD), mTOR and MyHC expression levels, and by markedly upregulating ubiquitin ligase (atrogin1) and muscle RING­finger protein­1 (MURF1) expression levels. Similarly, in an in vitro model of TNF­α­induced myotube atrophy, the western blotting results indicated that FoxO6 expression levels were decreased, whereas atrogin1, MURF1, FoxO1 and FoxO3a expression levels were increased compared with the control group. Therefore, the results indicated that, unlike FoxO1 or FoxO3a, FoxO6 maintained C2C12 myotubes and protected against atrophy. Consistent with the in vitro data, similar results were observed in vivo. Collectively, the results of the present study suggested that FoxO6 served a critical role in muscle cell metabolism in vitro and in vivo, and might serve as a promising therapeutic target for ameliorating skeletal muscle atrophy.

14.
J Cell Mol Med ; 25(12): 5372-5380, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33988296

RESUMO

The aim of this study was to explore the role of sulfasalazine on proliferation and metastasis in gastric cancer by inhibition of xCT. The relationships between clinical characteristics and xCT expression were analysed. An immunohistochemical staining assay and Western blot were performed among gastric cancers and normal gastric tissues. qPCR and Western blot were also used to evaluate the mRNA and protein expression in the normal gastric cell and eight gastric cancer cells, respectively. CCK-8 and colony formation assays were used to evaluate the effect of sulfasalazine on the proliferation and colony formation ability of three gastric cancers. The effect of sulfasalazine on the migration and invasion abilities of three cancer cells was assessed by the Transwell assay. xCT protein is up-regulated in gastric cancer specimens and cells. Three gastric cancer cells with high, medium and low expression of xCT were selected for the following analyses. CCK-8 assays revealed that sulfasalazine could attenuate the proliferation of HGC-27 and AGS. Also, the colony formation assay revealed that sulfasalazine might attenuate the colony formation ability in HGC-27 and AGS cells. Plus, the Transwell assays demonstrated that sulfasalazine might attenuate the migration and invasion abilities in HGC-27 and AGS cells. In conclusion, higher expression of xCT is associated with advanced tumour stage and poor overall survival of gastric cancer. Sulfasalazine can attenuate the proliferation, colony formation, metastasis and invasion of gastric cancer in vitro. Further study is required to validate our findings.


Assuntos
Sistema y+ de Transporte de Aminoácidos/antagonistas & inibidores , Anti-Inflamatórios não Esteroides/farmacologia , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Sulfassalazina/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Humanos , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Células Tumorais Cultivadas
15.
J Am Heart Assoc ; 10(10): e020361, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33955229

RESUMO

Background Intensive systolic blood pressure treatment (<120 mm Hg) in SPRINT (Systolic Blood Pressure Intervention Trial) improved survival compared with standard treatment (<140 mm Hg) over a median follow-up of 3.3 years. We projected life expectancy after observed follow-up in SPRINT using SPRINT-eligible participants in the NHLBI-PCS (National Heart, Lung, and Blood Institute Pooled Cohorts Study). Methods and Results We used propensity scores to weight SPRINT-eligible NHLBI-PCS participants to resemble SPRINT participants. In SPRINT participants, we estimated in-trial survival (<4 years) using a time-based flexible parametric survival model. In SPRINT-eligible NHLBI-PCS participants, we estimated posttrial survival (≥4 years) using an age-based flexible parametric survival model and applied the formula to SPRINT participants to predict posttrial survival. We projected overall life expectancy for each SPRINT participant and compared it to parametric regression (eg, Gompertz) projections based on SPRINT data alone. We included 8584 SPRINT and 10 593 SPRINT-eligible NHLBI-PCS participants. After propensity weighting, mean (SD) age was 67.9 (9.4) and 68.2 (8.8) years, and 35.5% and 37.6% were women in SPRINT and NHLBI-PCS, respectively. Using the NHLBI-PCS-based method, projected mean life expectancy from randomization was 21.0 (7.4) years with intensive and 19.1 (7.2) years with standard treatment. Using the Gompertz regression, life expectancy was 11.2 (2.3) years with intensive and 10.5 (2.2) years with standard treatment. Conclusions Combining SPRINT and NHLBI-PCS observed data likely offers a more realistic estimate of life expectancy than parametrically extrapolating SPRINT data alone. These results offer insight into the potential long-term effectiveness of intensive SBP goals.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Ensaios Clínicos como Assunto , Previsões , Hipertensão/tratamento farmacológico , Idoso , Feminino , Seguimentos , Humanos , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Masculino , Pontuação de Propensão , Fatores de Risco , Taxa de Sobrevida/tendências , Sístole , Estados Unidos/epidemiologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-33796969

RESUMO

BACKGROUND: Since the CRYSTAL-AF trial, implantation and usage of implantable loop recorder (ICM) after cryptogenic stroke (CS) for detection of atrial fibrillation (AF) has increased. However, it is unclear which CS patients would most benefit from long term ICM monitoring. This study aims to determine the risk factors in patients that would confer maximum benefit from ICM placement following CS. METHODS: A Columbia University Institutional Review Board (IRB) approved retrospective analysis of medical records of 125 patients with CS followed by implantation of ICM was evaluated. Univariable and multivariable time-to-event analyses were performed on demographics, hours of activity and variability (HRV), stroke location, thrombosis etiology, and CHA2DS2 - VASc score. The primary outcome was presence of ICM-detected AF defined as AF lasting at least 2 min. RESULTS: One hundred twenty-five patients (mean 67.6 years ± 2.4 years, 60% male) were followed for at least 3 months. Twenty-two patients (18%) were found to have clinically verified detected AF; median of time to detection was 95 days. Upon univariable demographic analysis followed by multivariable Cox regression analysis, individuals with age 75 or older (HR: 3.987, p = 0.0046) or LVEF 40% and lower (HR: 3.056, p = 0.0213) had significantly higher risk of AF. Diabetics also had a lower AF detection in multivariable analysis (HR: 0.128, p = 0.0466). CONCLUSIONS: Age 75 or older and LVEF ≤40% were the factors on multivariable analysis that predicted AF detection. Diabetes is a possible significant factor which should be evaluated further. CHA2DS2 - VASc score was notably not predictive of AF detected on ICM.

17.
Circulation ; 143(24): 2384-2394, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33855861

RESUMO

BACKGROUND: In LABBPS (Los Angeles Barbershop Blood Pressure Study), pharmacist-led hypertension care in Los Angeles County Black-owned barbershops significantly improved blood pressure control in non-Hispanic Black men with uncontrolled hypertension at baseline. In this analysis, 10-year health outcomes and health care costs of 1 year of the LABBPS intervention versus control are projected. METHODS: A discrete event simulation of hypertension care processes projected blood pressure, medication-related adverse events, fatal and nonfatal cardiovascular disease events, and noncardiovascular disease death in LABBPS participants. Program costs, total direct health care costs (2019 US dollars), and quality-adjusted life-years (QALYs) were estimated for the LABBPS intervention and control arms from a health care sector perspective over a 10-year horizon. Future costs and QALYs were discounted 3% annually. High and intermediate cost-effectiveness thresholds were defined as <$50 000 and <$150 000 per QALY gained, respectively. RESULTS: At 10 years, the intervention was projected to cost an average of $2356 (95% uncertainty interval, -$264 to $4611) more per participant than the control arm and gain 0.06 (95% uncertainty interval, 0.01-0.10) QALYs. The LABBPS intervention was highly cost-effective, with a mean cost of $42 717 per QALY gained (58% probability of being highly and 96% of being at least intermediately cost-effective). Exclusive use of generic drugs improved the cost-effectiveness to $17 162 per QALY gained. The LABBPS intervention would be only intermediately cost-effective if pharmacists were less likely to intensify antihypertensive medications when systolic blood pressure was ≥150 mm Hg or if pharmacist weekly time driving to barbershops increased. CONCLUSIONS: Hypertension care delivered by clinical pharmacists in Black barbershops is a highly cost-effective way to improve blood pressure control in Black men.

18.
Plant Signal Behav ; 16(7): 1913310, 2021 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-33853500

RESUMO

Phosphate (Pi) deficiency is one of the major adverse factors limiting plant growth and production. Enhanced RH development is thought to be the typical root morphological response under Pi deficiency, which will enhance the utilization of Pi resources from soil. Here, we report that MYB30-EIN3 module is functionally implicated in Pi deficiency-induced RH development in Arabidopsis. MYB30 and EIN3 antagonistically regulate RH growth via transcriptional regulation of RSL4 as well as other PSR genes, resulting in fine-tuned Pi uptake under Pi deficiency.

19.
J Am Coll Cardiol ; 77(16): 1977-1990, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33888247

RESUMO

BACKGROUND: Intensive systolic blood pressure (SBP) treatment prevents cardiovascular disease (CVD) events in patients with high CVD risk on average, though benefits likely vary among patients. OBJECTIVES: The aim of this study was to predict the magnitude of benefit (reduced CVD and all-cause mortality risk) along with adverse event (AE) risk from intensive versus standard SBP treatment. METHODS: This was a secondary analysis of SPRINT (Systolic Blood Pressure Intervention Trial). Separate benefit outcomes were the first occurrence of: 1) a CVD composite of acute myocardial infarction or other acute coronary syndrome, stroke, heart failure, or CVD death; and 2) all-cause mortality. Treatment-related AEs of interest included hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, and acute kidney injury. Modified elastic net Cox regression was used to predict absolute risk for each outcome and absolute risk differences on the basis of 36 baseline variables available at the point of care with intensive versus standard treatment. RESULTS: Among 8,828 SPRINT participants (mean age 67.9 years, 35% women), 600 CVD composite events, 363 all-cause deaths, and 481 treatment-related AEs occurred over a median follow-up period of 3.26 years. Individual participant risks were predicted for the CVD composite (C index = 0.71), all-cause mortality (C index = 0.75), and treatment-related AEs (C index = 0.69). Higher baseline CVD risk was associated with greater benefit (i.e., larger absolute CVD risk reduction). Predicted CVD benefit and predicted increased treatment-related AE risk were correlated (Spearman correlation coefficient = -0.72), and 95% of participants who fell into the highest tertile of predicted benefit also had high or moderate predicted increases in treatment-related AE risk. Few were predicted as high benefit with low AE risk (1.8%) or low benefit with high AE risk (1.5%). Similar results were obtained for all-cause mortality. CONCLUSIONS: SPRINT participants with higher baseline predicted CVD risk gained greater absolute benefit from intensive treatment. Participants with high predicted benefit were also most likely to experience treatment-related AEs, but AEs were generally mild and transient. Patients should be prioritized for intensive SBP treatment on the basis of higher predicted benefit. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062).


Assuntos
Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Seleção de Pacientes , Idoso , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Feminino , Seguimentos , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Medição de Risco
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