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1.
Cytokine Growth Factor Rev ; 54: 32-42, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32747157

RESUMO

The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses including SARS-CoV and MERS-CoV, which can cause fatal lower respiratory tract infection. Likewise, SARS-CoV2 infection can be fatal as the disease advances to pneumonia, followed by acute respiratory distress syndrome (ARDS). The development of lethal clinical symptons is associated with an exaggerated production of inflammatory cytokines, referred to as the cytokine storm, is a consequence of a hyperactivated immune response aginst the infection. In this article, we discuss the pathogenic consequences of the cytokine storm and its relationship with COVID-19 associated risk factors. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 into a 'Cytokine Super Cyclone'. We also evaluate the antiviral immune responses provided by BCG vaccination and the potential role of 'trained immunity' in early protection against SARS-CoV2.


Assuntos
Vacina BCG/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Síndrome da Liberação de Citocina/prevenção & controle , Citocinas/sangue , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Doenças Cardiovasculares/patologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Diabetes Mellitus/patologia , Humanos , Hipertensão/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Mycobacterium bovis/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , Fatores de Risco , Síndrome Respiratória Aguda Grave/imunologia , Vacinação
2.
PLoS One ; 15(8): e0237359, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790789

RESUMO

BACKGROUND: Patients diagnosed with obstructive sleep apnea (OSA), who also consume prescription opioids, have a greater likelihood of morbidity and mortality. This study evaluated whether a primary care team, focused on chronic pain care management, could use a validated questionnaire (STOP-Bang) and motivational follow-up, to increase identification and treatment of OSA. METHODS: This study was a retrospective, dual arm, pre/post controlled study. Participants of this study included the complete chronic pain management sub group treated by this primary care team. Participants were ≥ 18 years old and prescribed daily opioids for treatment of chronic pain. All participants had a multifaceted, individualized, educational meeting that included completing a STOP-Bang questionnaire. Participants who received a score ≥ three were advised to follow up with their primary care physician. Participants were seen quarterly throughout the study. RESULTS: The primary outcome of this study was that 65% of participants with likely OSA were using CPAP for a minimum of 12 months (range of 12-25 months, 18-month average) post-intervention vs. 37% CPAP-use in the control group (12 months of observation), both groups were chronic opioid users with OSA. This was a 28% relative improvement (p = 0.0034). A secondary outcome was that 8.9% of non-prior CPAP users obtained CPAP post- intervention; a 56.7% pre-post improvement (p = 0.0064, x2 = 10.08 with 1 degree of freedom). Also, participants who were likely to have OSA (STOP-Bang score ≥ 3 or had a positive polysomnography (AHI >5 with comorbidities)) compared to those unlikely to have OSA (STOP-Bang score <3 or had a negative polysomnography (AHI <5)) in this study were more likely to be male, have a higher BMI, have hypertension, have cardiovascular disease and/or have diabetes (all types). CONCLUSION: Team based care management for participants taking prescription opioids, where STOP-Bang questionnaires were completed, were associated with an increase in the identification and treatment of OSA.


Assuntos
Manejo da Dor/métodos , Dor/patologia , Apneia Obstrutiva do Sono/diagnóstico , Adulto , Idoso , Analgésicos Opioides/uso terapêutico , Índice de Massa Corporal , Doença Crônica , Feminino , Humanos , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Dor/complicações , Dor/tratamento farmacológico , Polissonografia , Atenção Primária à Saúde , Estudos Retrospectivos , Fatores Sexuais , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Inquéritos e Questionários
4.
PLoS One ; 15(7): e0235709, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32650339

RESUMO

BACKGROUND: Since 2005, the Smoking Treatment for Ontario Patients (STOP) program has provided smoking cessation treatment of varying form and intensity to smokers through 11 distinct treatment models, either in-person at partnering healthcare organizations or remotely via web or telephone. We aimed to characterize the patient populations reached by different treatment models. METHODS: We linked self-report data to health administrative databases to describe sociodemographics, physical and mental health comorbidity, healthcare utilization and costs. Our sample consisted of 107,302 patients who enrolled between 18Oct2005 and 31Mar2016, across 11 models operational during different time periods. RESULTS: Patient populations varied on sociodemographics, comorbidity burden, and healthcare usage. Enrollees in the Web-based model were youngest (median age: 39; IQR: 29-49), and enrollees in primary care-based Family Health Teams were oldest (median: 51; IQR: 40-60). Chronic Obstructive Pulmonary Disease and hypertension were the most common physical health comorbidities, twice as prevalent in Family Health Teams (32.3% and 30.8%) than in the direct-to-smoker (Web and Telephone) and Pharmacy models (13.5%-16.7% and 14.7%-17.7%). Depression, the most prevalent mental health diagnosis, was twice as prevalent in the Addiction Agency (52.1%) versus the Telephone model (25.3%). Median healthcare costs in the two years up to enrollment ranged from $1,787 in the Telephone model to $9,393 in the Addiction Agency model. DISCUSSION: While practitioner-mediated models in specialized and primary care settings reached smokers with more complex healthcare needs, alternative settings appear better suited to reach younger smokers before such comorbidities develop. Although Web and Telephone models were expected to have fewer barriers to access, they reached a lower proportion of patients in rural areas and of lower socioeconomic status. Findings suggest that in addition to population-based strategies, embedding smoking cessation treatment into existing healthcare settings that reach patient populations with varying disparities may enhance equitable access to treatment.


Assuntos
Aceitação pelo Paciente de Cuidados de Saúde , Fumantes/psicologia , Adulto , Comorbidade , Estudos Transversais , Depressão/epidemiologia , Depressão/patologia , Feminino , Custos de Cuidados de Saúde , Humanos , Hipertensão/epidemiologia , Hipertensão/patologia , Internet , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Abandono do Hábito de Fumar , Inquéritos e Questionários , Telefone
5.
PLoS One ; 15(7): e0236034, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702046

RESUMO

BACKGROUND: Evidence suggests that the single-disease paradigm does not accurately reflect the individual experience, with increasing prevalence of chronic disease multimorbidity, and subtle yet important differences in types of co-occurring diseases. Knowledge of multimorbidity patterns can aid clarification of individual-level burden and needs, to inform prevention and treatment strategies. This study aimed to estimate the prevalence of multimorbidity in Jamaica, identify population subgroups with similar and distinct disease profiles, and examine consistency in patterns identified across statistical techniques. METHODS: Latent class analysis (LCA) was used to examine multimorbidity patterns in a sample of 2,551 respondents aged 15-74 years, based on data from the nationally representative Jamaica Health and Lifestyle Survey 2007/2008 and self-reported presence/absence of 11 chronic conditions. Secondary analyses compared results with patterns identified using exploratory factor analysis (EFA). RESULTS: Nearly one-quarter of the sample (24.1%) were multimorbid (i.e. had ≥2 diseases), with significantly higher burden in females compared to males (31.6% vs. 16.1%; p<0.001). LCA revealed four distinct classes, including a predominant Relatively Healthy class, comprising 52.7% of the sample, with little to no morbidity. The remaining three classes were characterized by varying degrees and patterns of multimorbidity and labelled Metabolic (30.9%), Vascular-Inflammatory (12.2%), and Respiratory (4.2%). Four diseases determined using physical assessments (obesity, hypertension, diabetes, hypercholesterolemia) were primary contributors to multimorbidity patterns overall. EFA identified three patterns described as "Vascular" (hypertension, obesity, hypercholesterolemia, diabetes, stroke); "Respiratory" (asthma, COPD); and "Cardio-Mental-Articular" (cardiovascular disease, arthritis, mental disorders). CONCLUSION: This first study of multimorbidity in the Caribbean has revealed a high burden of co-existing conditions in the Jamaican population, that is predominantly borne by females. Consistency across methods supports the validity of patterns identified. Future research into the causes and consequences of multimorbidity patterns can guide development of clinical and public health strategies that allow for targeted prevention and intervention.


Assuntos
Análise de Classes Latentes , Multimorbidade , Adolescente , Adulto , Idoso , Asma/complicações , Asma/epidemiologia , Asma/patologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão/patologia , Jamaica/epidemiologia , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/epidemiologia , Transtornos Mentais/patologia , Pessoa de Meia-Idade , Prevalência , Autorrelato , Fatores Sexuais , Adulto Jovem
6.
EBioMedicine ; 57: 102880, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32645614

RESUMO

BACKGROUND: Information regarding risk factors associated with severe coronavirus disease (COVID-19) is limited. This study aimed to develop a model for predicting COVID-19 severity. METHODS: Overall, 690 patients with confirmed COVID-19 were recruited between 1 January and 18 March 2020 from hospitals in Honghu and Nanchang; finally, 442 patients were assessed. Data were categorised into the training and test sets to develop and validate the model, respectively. FINDINGS: A predictive HNC-LL (Hypertension, Neutrophil count, C-reactive protein, Lymphocyte count, Lactate dehydrogenase) score was established using multivariate logistic regression analysis. The HNC-LL score accurately predicted disease severity in the Honghu training cohort (area under the curve [AUC]=0.861, 95% confidence interval [CI]: 0.800-0.922; P<0.001); Honghu internal validation cohort (AUC=0.871, 95% CI: 0.769-0.972; P<0.001); and Nanchang external validation cohort (AUC=0.826, 95% CI: 0.746-0.907; P<0.001) and outperformed other models, including CURB-65 (confusion, uraemia, respiratory rate, BP, age ≥65 years) score model, MuLBSTA (multilobular infiltration, hypo-lymphocytosis, bacterial coinfection, smoking history, hypertension, and age) score model, and neutrophil-to-lymphocyte ratio model. The clinical significance of HNC-LL in accurately predicting the risk of future development of severe COVID-19 was confirmed. INTERPRETATION: We developed an accurate tool for predicting disease severity among COVID-19 patients. This model can potentially be used to identify patients at risks of developing severe disease in the early stage and therefore guide treatment decisions. FUNDING: This work was supported by the National Nature Science Foundation of China (grant no. 81972897) and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2015).


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Índice de Gravidade de Doença , Betacoronavirus , Proteína C-Reativa/análise , Síndrome da Liberação de Citocina/patologia , Feminino , Humanos , Hipertensão/patologia , L-Lactato Desidrogenase/análise , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Pandemias , Prognóstico , Estudos Retrospectivos
7.
Life Sci ; 258: 118124, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32702443

RESUMO

AIMS: Ketogenic diet (KD) has been proposed to be an effective lifestyle intervention for metabolic syndrome. However, the effects of KD on hypertension have not been well investigated. The present study aimed to investigate the effects and underling mechanisms of KD on hypertension in spontaneously hypertensive rats (SHRs). MATERIALS AND METHODS: SHRs were subjected to normal diet or KD for 4 weeks, starting at the age of 10 weeks. Then, the blood pressure and vascular function were assessed. Next, the eNOS expression, inflammatory factors and relative signaling pathway were examined. Human umbilical vein endothelial cells were used to investigate the underlying mechanism account for the effect of ketone on inflammation and eNOS expression. KEY FINDINGS: Compared with the normal diet, KD was indicated to aggravate hypertension and impaire endothelium-dependent relaxation in mesenteric arteries of SHRs. eNOS and CD31 expression in mesenteric arteries were also significantly suppressed by KD. In addition, KD markedly increased the activation of NF-κB pathway and the expression of IL1-ß and TNF-α. In vitro, results showed that inhibition of NF-κB could rescue the adverse effects of ketone body and TGF-ß on eNOS expression and inflammation response. SIGNIFICANCE: Our study indicated that KD impaired endothelium-dependent relaxation in mesenteric arteries and aggravated the development of hypertension in SHRs, suggesting that it should be more cautious to apply KD into clinical application in hypertensive individuals.


Assuntos
Dieta Cetogênica , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Hipertensão/metabolismo , Hipertensão/patologia , NF-kappa B/metabolismo , Animais , Biomarcadores/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Corpos Cetônicos/metabolismo , Masculino , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/patologia , Óxido Nítrico Sintase Tipo III/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Ratos Endogâmicos SHR , Vasodilatação , Perda de Peso
8.
PLoS One ; 15(7): e0236602, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716977

RESUMO

A significant relationship exists between elevated uric acid concentration and both prevalent and incident hypertension; however, data regarding the influence of higher uric acid concentration at baseline on blood pressure control by antihypertensive drugs is scarce. Thus, a prospective cohort study was performed. The study outcome was the non-attainment of optimal blood pressure (NOBP). NOBP level was defined according to the Japanese hypertension guideline. This study enrolled a Japanese community-based cohort (N = 8,664; age 65.5 ± 6.4 years; women, 55.0%) who were not using antihypertensive drugs on the first visit for a health check-up program but started using antihypertensive drug(s) on the next-year visit. The participants were classified into quartiles based basic uric acid concentration. Odds ratios (ORs) were calculated for NOBP as the primary outcome measure. Multivariable logistic analysis showed that quartile 4 was significantly associated with NOBP when quartile 1 was set as the reference (OR (95% confidence interval), 1.36 (1.16-1.59), p<0.01), adjusted for potential confounders, such as age, sex, body mass index, presence of diabetes/dyslipidemia/chronic kidney disease (CKD), history of cardiovascular disease, daily drinking, and current smoking. In the subgroup analysis of female participants and participants with diabetes and CKD, a significant association was observed between +1 mg/dL of uric acid and NOBP. Higher uric acid concentration at baseline was significantly associated with NOBP on the first use of antihypertensive drug(s).


Assuntos
Pressão Sanguínea/fisiologia , Ácido Úrico/sangue , Idoso , Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus/patologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Insuficiência Renal Crônica/patologia
9.
J Infect ; 81(4): e18-e25, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32634459

RESUMO

OBJECTIVE: Coronavirus Disease 2019 (COVID-19) is a pandemic. This systematic review compares mortality risk factors including clinical, demographic and laboratory features of COVID-19, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The aim is to provide new strategies for COVID-19 prevention and treatment. METHODS: We performed a systematic review with meta-analysis, using five databases to compare the predictors of death for COVID-19, SARS and MERS. A random-effects model meta-analysis calculated odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: 845 articles up through 11/4/2020 were retrieved, but only 28 studies were included in this meta-analysis. The results showed that males had a higher likelihood of death than females (OR = 1.82, 95% CI 1.56-2.13). Age (OR = 7.86, 95% CI 5.46-11.29), diabetes comorbidity (OR = 3.73, 95% CI 2.35-5.90), chronic lung disease (OR = 3.43, 95% CI 1.80-6.52) and hypertension (OR = 3.38, 95% CI 2.45-4.67) were the mortality risk factors. The laboratory indicators lactic dehydrogenase (OR = 37.52, 95% CI 24.68-57.03), C-reactive protein (OR = 12.11, 95% CI 5.24-27.98), and neutrophils (OR = 17.56, 95% CI 10.67-28.90) had stronger correlations with COVID-19 mortality than with SARS or MERS mortality. Consolidation and ground-glass opacity imaging features were similar among COVID-19, SARS, and MERS patients. CONCLUSIONS: COVID-19's mortality factors are similar to those of SARS and MERS. Age and laboratory indicators could be effective predictors of COVID-19 mortality outcomes.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Fatores de Risco , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/mortalidade , Betacoronavirus , Proteína C-Reativa/análise , Diabetes Mellitus/patologia , Feminino , Humanos , Hipertensão/patologia , L-Lactato Desidrogenase/sangue , Pneumopatias/patologia , Masculino , Coronavírus da Síndrome Respiratória do Oriente Médio , Neutrófilos/citologia , Pandemias , Vírus da SARS , Fatores Sexuais
10.
Eur Rev Med Pharmacol Sci ; 24(10): 5788-5796, 2020 05.
Artigo em Inglês | MEDLINE | ID: covidwho-547469

RESUMO

OBJECTIVE: Lopinavir/ritonavir has modest antiviral activity against severe acute respiratory syndrome coronavirus 2. The aim was to investigate the viral kinetics and factors associated with viral clearance during lopinavir/ritonavir-based combination treatment in non-severe patients. PATIENTS AND METHODS: Sixty-four patients were retrospectively enrolled. Viral RNA was detected by real-time RT-PCR assay from sputum or throat swab samples at different time points. The patterns of viral kinetics were characterized, and factors associated with rapid viral clearance, which was defined as viral RNA undetectable within two weeks, were analyzed using multivariate logistic regression analyses. RESULTS: All patients achieved viral RNA negativity and were discharged from the hospital. Furthermore, 48 (75%) and 16 (25%) patients achieved rapid and delayed viral clearance, respectively. The lymphocyte counts of rapid viral clearance patients (1.40 [1.20-1.80] × 109/L) were higher, when compared to delayed viral clearance patients (1.00 [0.70-1.47] × 109/L) (p=0.024). The multivariate logistic analysis revealed that high lymphocyte count (≥1.3×109/L) is an independent factor associated with rapid viral clearance (OR=7.62, 95% CI=1.15-50.34, p=0.035). CONCLUSIONS: The viral shedding exhibited different patterns during treatment. Immune insufficiency is responsible for the delayed viral clearance, suggesting that an immunomodulator should be considered to promote viral clearance in patients with low lymphocyte counts.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Lopinavir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Adulto , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Fezes/virologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/patologia , Modelos Logísticos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Pneumonia Viral/virologia , RNA Viral/análise , Estudos Retrospectivos , Índice de Gravidade de Doença , Carga Viral
11.
Clin Exp Hypertens ; 42(8): 748-752, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-32564622

RESUMO

OBJECTIVE: This study aimed to explore the mechanism of hypertensive brain damage from ferroptosis pathway. METHODS: Ten 22-week-old SHR rats were labeled as hypertension group(HBP), while ten WKY rats of comparable age, weight were used as normal blood pressure group(NBP). After 2 weeks of feeding, hypertensive brain damage was observed by comparing the pathological changes of brain tissue in SHR rats and WKY rats. Furthermore, the expression of GPX4 in the cerebral cortex was detected by immunofluorescence. The content of GSH was determined by spectrophotometer. The content of iron was detected by ferrous chromite colorimetry. And the content of MDA was determined by spectrophotometer. Compare the difference to investigate the role of ferroptosis mechanism in hypertensive brain damage. RESULTS: Brain damage occurred in 24-week-old SHR rats compared with WKY rats. In the HBP, the GPX4 and GSH were significantly lower than those in the NBP, and the total iron content and MDA were significantly increased. CONCLUSION: Thses findings suggest ferroptosis is closely related to hypertensive brain damage. Elevated blood pressure leads to iron overload in the brain. Excessive iron increases oxidative stress and lipid peroxidation in the brain, and eventually causes brain damage.


Assuntos
Encéfalo/patologia , Ferroptose , Hipertensão/patologia , Animais , Pressão Sanguínea , Encéfalo/metabolismo , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Peroxidação de Lipídeos , Masculino , Estresse Oxidativo/fisiologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
12.
Eur Rev Med Pharmacol Sci ; 24(10): 5788-5796, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32495917

RESUMO

OBJECTIVE: Lopinavir/ritonavir has modest antiviral activity against severe acute respiratory syndrome coronavirus 2. The aim was to investigate the viral kinetics and factors associated with viral clearance during lopinavir/ritonavir-based combination treatment in non-severe patients. PATIENTS AND METHODS: Sixty-four patients were retrospectively enrolled. Viral RNA was detected by real-time RT-PCR assay from sputum or throat swab samples at different time points. The patterns of viral kinetics were characterized, and factors associated with rapid viral clearance, which was defined as viral RNA undetectable within two weeks, were analyzed using multivariate logistic regression analyses. RESULTS: All patients achieved viral RNA negativity and were discharged from the hospital. Furthermore, 48 (75%) and 16 (25%) patients achieved rapid and delayed viral clearance, respectively. The lymphocyte counts of rapid viral clearance patients (1.40 [1.20-1.80] × 109/L) were higher, when compared to delayed viral clearance patients (1.00 [0.70-1.47] × 109/L) (p=0.024). The multivariate logistic analysis revealed that high lymphocyte count (≥1.3×109/L) is an independent factor associated with rapid viral clearance (OR=7.62, 95% CI=1.15-50.34, p=0.035). CONCLUSIONS: The viral shedding exhibited different patterns during treatment. Immune insufficiency is responsible for the delayed viral clearance, suggesting that an immunomodulator should be considered to promote viral clearance in patients with low lymphocyte counts.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Lopinavir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Adulto , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Fezes/virologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/patologia , Modelos Logísticos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Pneumonia Viral/virologia , RNA Viral/análise , Estudos Retrospectivos , Índice de Gravidade de Doença , Carga Viral
13.
PLoS One ; 15(6): e0234049, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32502169

RESUMO

The literature on the global burden of noncommunicable diseases (NCDs) contrasts a spiraling epidemic centered in low-income countries with low levels of awareness, risk factor control, infrastructure, personnel and funding. There are few data-based reports of broad and interconnected strategies to address these challenges where they hit hardest. Kisoro district in Southwest Uganda is rural, remote, over-populated and poor, the majority of its population working as subsistence farmers. This paper describes the 10-year experience of a tri-partite collaboration between Kisoro District Hospital, a New York teaching hospital, and a US-based NGO delivering hypertension services to the district. Using data from patient and pharmacy registers and a random sample of charts reviewed manually, we describe both common and often-overlooked barriers to quality care (clinic overcrowding, drug stockouts, provider shortages, visit non-adherence, and uninformative medical records) and strategies adopted to address these barriers (locally-adapted treatment guidelines, patient-clinic-pharmacy cost sharing, appointment systems, workforce development, patient-provider continuity initiatives, and ongoing data monitoring). We find that: 1) although following CVD risk-based treatment guidelines could safely allocate scarce medications to the highest-risk patients first, national guidelines emphasizing treatment at blood pressures over 140/90 mmHg ignore the reality of "stockouts" and conflict with this goal; 2) often-overlooked barriers to quality care such as poor quality medical records, clinic disorganization and local employment practices are surmountable; 3) cost-sharing initiatives partially fill the gap during stockouts of government supplied medications, but still may be insufficient for the poorest patients; 4) frequent prolonged lapses in care may be the norm for most known hypertensives in rural SSA, and 5) ongoing data monitoring can identify local barriers to quality care and provide the impetus to ameliorate them. We anticipate that our 10-year experience adapting to the complex challenges of hypertension management and a granular description of the solutions we devised will be of benefit to others managing chronic disease in similar rural African communities.


Assuntos
Hipertensão/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Assistência à Saúde , Feminino , Guias como Assunto , Hospitais de Distrito , Humanos , Hipertensão/patologia , Conhecimento , Masculino , Pessoa de Meia-Idade , Reorganização de Recursos Humanos , Risco , População Rural , Cooperação e Adesão ao Tratamento , Uganda , Adulto Jovem
14.
PLoS One ; 15(6): e0234547, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555714

RESUMO

Estimating the prevalence of cardiovascular diseases (CVDs) and risk factors among the Roma population, the largest minority in Europe, and investigating the role of genetic or environmental/behavioral risk factors in CVD development are important issues in countries where they are significant minority. This study was designed to estimate the genetic susceptibility of the Hungarian Roma (HR) population to essential hypertension (EH) and compare it to that of the general (HG) population. Twenty EH associated SNPs (in AGT, FMO3, MTHFR-NPPB, NPPA, NPPA-AS1, AGTR1, ADD1, NPR3-C5orf23, NOS3, CACNB2, PLCE1, ATP2B1, GNB3, CYP1A1-ULK3, UMOD and GNAS-EDN3) were genotyped using DNA samples obtained from HR (N = 1176) and HG population (N = 1178) subjects assembled by cross-sectional studies. Allele frequencies and genetic risk scores (unweighted and weighted genetic risk scores (GRS and wGRS, respectively) were calculated for the study groups and compared to examine the joint effects of the SNPs. The susceptibility alleles were more frequent in the HG population, and both GRS and wGRS were found to be higher in the HG population than in the HR population (GRS: 18.98 ± 3.05 vs. 18.25 ± 2.97, p<0.001; wGRS: 1.4 [IQR: 0.93-1.89] vs. 1.52 [IQR: 0.99-2.00], p<0.01). Twenty-seven percent of subjects in the HR population were in the bottom fifth (GRS ≤ 16) of the risk allele count compared with 21% of those in the HG population. Thirteen percent of people in the HR group were in the top fifth (GRS ≥ 22) of the GRS compared with 21% of those in the HG population (p<0.001), i.e., the distribution of GRS was found to be left-shifted in the HR population compared to the HG population. The Roma population seems to be genetically less susceptible to EH than the general one. These results support preventive efforts to lower the risk of developing hypertension by encouraging a healthy lifestyle.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Hipertensão/genética , Adulto , Alelos , Biomarcadores/sangue , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Hungria/epidemiologia , Hipertensão/sangue , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Roma/genética
15.
Clin Immunol ; 215: 108450, 2020 06.
Artigo em Inglês | MEDLINE | ID: covidwho-172295

RESUMO

Acute respiratory distress syndrome (ARDS) is a devastating clinical manifestation of COVID-19 pneumonia and is mainly based on an immune-driven pathology. Mounting evidence suggests that COVID-19 is fueled by a maladaptive host inflammatory response that involves excessive activation of innate immune pathways. While a "cytokine storm" involving IL-6 and other cytokines has been documented, complement C3 activation has been implicated as an initial effector mechanism that exacerbates lung injury in preclinical models of SARS-CoV infection. C3-targeted intervention may provide broader therapeutic control of complement-mediated inflammatory damage in COVID-19 patients. Herein, we report the clinical course of a patient with severe ARDS due to COVID-19 pneumonia who was safely and successfully treated with the compstatin-based complement C3 inhibitor AMY-101.


Assuntos
Betacoronavirus/efeitos dos fármacos , Ativação do Complemento/efeitos dos fármacos , Complemento C3/antagonistas & inibidores , Inativadores do Complemento/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Peptídeos Cíclicos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Idoso , Antivirais/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/imunologia , Fibrilação Atrial/patologia , Fibrilação Atrial/virologia , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Humanos , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/imunologia , Hipercolesterolemia/patologia , Hipercolesterolemia/virologia , Hipertensão/tratamento farmacológico , Hipertensão/imunologia , Hipertensão/patologia , Hipertensão/virologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Masculino , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Resultado do Tratamento
16.
Cytokine Growth Factor Rev ; 53: 43-52, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32409230

RESUMO

The current pandemic outbreak of COVID-19 originated from Wuhan, China. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with significant mortality and morbidity rate. The severe risk factors are commonly detected in patients of older age and with medical comorbidities like cancer and diabetes. Scientists and doctors have scrambled to gain knowledge about the novel virus and its pathophysiology in order to discover possible therapeutic regimens and vaccines for COVID-19. The therapeutic strategies like targeting the viral genome emphasize the promising approach to target COVID-19. Additionally, blocking the receptor, ACE2 via the neutralizing antibodies for viral escape that prevents it from entering into the cells provides another therapeutic regimen. In this review article, we have presented the effect of SARS-CoV-2 infection in comorbid patients and discussed organ failure caused by this virus. Based on the data available from the scientific literature and ongoing clinical trials, we have focused on therapeutic strategies. We hope that we would fill the gaps that puzzled the researchers and clinicians with the best of our knowledge collected for the betterment of the patients for the coming future.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/patologia , Diabetes Mellitus/patologia , Insuficiência de Múltiplos Órgãos/patologia , Neoplasias/patologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus/genética , Betacoronavirus/patogenicidade , Comorbidade , Humanos , Hidroxicloroquina/uso terapêutico , Hipertensão/patologia , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Pandemias , Peptidil Dipeptidase A/metabolismo
17.
Stroke ; 51(6): 1835-1843, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32397936

RESUMO

Background and Purpose- oxLDL (oxidized low-density lipoprotein) has been known for its potential to induce endothelial dysfunction and used as a major serological marker of oxidative stress. Recently, LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1), a lectin-like receptor for oxLDL, has attracted attention in studies of neuronal apoptosis and stroke. We aim to investigate the impact of LOX-1-deficiency on spontaneous hypertension-related brain damage in the present study. Methods- We generated a LOX-1 deficient strain on the genetic background of stroke-prone spontaneously hypertensive rat (SHRSP), an animal model of severe hypertension and spontaneous stroke. In this new disease model with stroke-proneness, we monitored the occurrence of brain abnormalities with and without salt loading by multiple procedures including T2 weighted magnetic resonance imaging and also explored circulatory miRNAs as diagnostic biomarkers for cerebral ischemic injury by microarray analysis. Results- Both T2 weighted magnetic resonance imaging abnormalities and physiological parameter changes could be detected at significantly delayed timing in LOX-1 knockout rats compared with wild-type SHRSP, in either case of normal rat chow and salt loading (P<0.005 in all instances; n=11-20 for SHRSP and n=13-23 for LOX-1 knockout rats). There were no significant differences in the form of magnetic resonance imaging findings between the strains. A number of miRNAs expressed in the normal rat plasma, including rno-miR-150-5p and rno-miR-320-3p, showed significant changes after spontaneous brain damage in SHRSP, whereas the corresponding changes were modest or almost unnoticeable in LOX-1 knockout rats. There appeared to be the lessening of correlation of postischemic miRNA alterations between the injured brain tissue and plasma in LOX-1 knockout rats. Conclusions- Our data show that deficiency of LOX-1 has a protective effect on spontaneous brain damage in a newly generated LOX-1-deficient strain of SHRSP. Further, our analysis of miRNAs as biomarkers for ischemic brain damage supports a potential involvement of LOX-1 in blood brain barrier disruption after cerebral ischemia. Visual Overview- An online visual overview is available for this article.


Assuntos
Barreira Hematoencefálica , Isquemia Encefálica , Deleção de Genes , Hipertensão , Receptores Depuradores Classe E/deficiência , Acidente Vascular Cerebral , Animais , Barreira Hematoencefálica/lesões , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Isquemia Encefálica/sangue , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , MicroRNA Circulante , Hipertensão/sangue , Hipertensão/genética , Hipertensão/patologia , MicroRNAs/sangue , MicroRNAs/genética , Ratos , Ratos Endogâmicos SHR , Ratos Transgênicos , Receptores Depuradores Classe E/metabolismo , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/patologia
18.
Diabetologia ; 63(8): 1500-1515, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32472191

RESUMO

AIMS/HYPOTHESIS: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m2; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION: clinicaltrials.gov NCT04324736.


Assuntos
Infecções por Coronavirus/patologia , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/virologia , Pneumonia Viral/patologia , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/complicações , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/terapia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipertensão/patologia , Pacientes Internados/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Pneumonia Viral/terapia , Prognóstico , Respiração Artificial/estatística & dados numéricos , Fatores de Risco
19.
Clin Immunol ; 215: 108450, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32360516

RESUMO

Acute respiratory distress syndrome (ARDS) is a devastating clinical manifestation of COVID-19 pneumonia and is mainly based on an immune-driven pathology. Mounting evidence suggests that COVID-19 is fueled by a maladaptive host inflammatory response that involves excessive activation of innate immune pathways. While a "cytokine storm" involving IL-6 and other cytokines has been documented, complement C3 activation has been implicated as an initial effector mechanism that exacerbates lung injury in preclinical models of SARS-CoV infection. C3-targeted intervention may provide broader therapeutic control of complement-mediated inflammatory damage in COVID-19 patients. Herein, we report the clinical course of a patient with severe ARDS due to COVID-19 pneumonia who was safely and successfully treated with the compstatin-based complement C3 inhibitor AMY-101.


Assuntos
Betacoronavirus/efeitos dos fármacos , Ativação do Complemento/efeitos dos fármacos , Complemento C3/antagonistas & inibidores , Inativadores do Complemento/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Peptídeos Cíclicos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Idoso , Antivirais/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/imunologia , Fibrilação Atrial/patologia , Fibrilação Atrial/virologia , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Humanos , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/imunologia , Hipercolesterolemia/patologia , Hipercolesterolemia/virologia , Hipertensão/tratamento farmacológico , Hipertensão/imunologia , Hipertensão/patologia , Hipertensão/virologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Masculino , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Resultado do Tratamento
20.
Virus Res ; 286: 198034, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32445872

RESUMO

The angiotensin-converting enzyme 2 receptor (ACE2) is expressed in epithelial cells of many tissues including the kidney, and has been identified to interact with human pathogenic coronaviruses, including SARS-CoV-2. Although diffuse alveolar damage and acute respiratory failure are the main features of COVID-19 infection, two recent studies demonstrate that kidney impairment in hospitalized COVID-19 patients is common, and that kidney involvement is associated with high risk of in-hospital death. Interestingly, studies in rats have demonstrated that high dietary sodium intake results in down-regulation of the ACE2 expression in kidney tissue. We hypothesize that low sodium status makes kidney involvement during the course of COVID-19 infection more likely due to upregulation of membrane bound ACE2 in the kidneys. We propose that sodium intake and status should be monitored carefully during severe COVID-19 infections, and that low sodium intake be corrected early in its course, despite a potential conflict regarding common dietary recommendations to restrict dietary sodium intake in patients with hypertension, diabetes, and kidney disease.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/genética , Rim/efeitos dos fármacos , Peptidil Dipeptidase A/genética , Pneumonia Viral/genética , Sódio na Dieta/farmacologia , Glicoproteína da Espícula de Coronavírus/genética , Animais , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Células Epiteliais/virologia , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Humanos , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/patologia , Hipertensão/virologia , Rim/metabolismo , Rim/patologia , Rim/virologia , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/metabolismo , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Ligação Proteica , Ratos , Ratos Endogâmicos SHR , Índice de Gravidade de Doença , Sódio na Dieta/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo
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