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1.
J Infect Dis ; 229(4): 999-1009, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37527470

RESUMO

BACKGROUND: The Global Influenza Hospital Surveillance Network (GIHSN) has since 2012 provided patient-level data on severe influenza-like-illnesses from >100 participating clinical sites worldwide based on a core protocol and consistent case definitions. METHODS: We used multivariable logistic regression to assess the risk of intensive care unit admission, mechanical ventilation, and in-hospital death among hospitalized patients with influenza and explored the role of patient-level covariates and country income level. RESULTS: The data set included 73 121 patients hospitalized with respiratory illness in 22 countries, including 15 660 with laboratory-confirmed influenza. After adjusting for patient-level covariates we found a 7-fold increase in the risk of influenza-related intensive care unit admission in lower middle-income countries (LMICs), compared with high-income countries (P = .01). The risk of mechanical ventilation and in-hospital death also increased by 4-fold in LMICs, though these differences were not statistically significant. We also find that influenza mortality increased significantly with older age and number of comorbid conditions. Across all severity outcomes studied and after controlling for patient characteristics, infection with influenza A/H1N1pdm09 was more severe than with A/H3N2. CONCLUSIONS: Our study provides new information on influenza severity in underresourced populations, particularly those in LMICs.


Assuntos
Influenza Humana , Humanos , Influenza Humana/epidemiologia , Vírus da Influenza A Subtipo H3N2 , Mortalidade Hospitalar , Hospitalização , Hospitais
2.
J Med Virol ; 95(1): e28153, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36110064

RESUMO

The cost of influenza and other respiratory virus infections should be determined to analyze the real burden of these diseases. We aimed to investigate the clinical outcomes and cost of illness due to respiratory virus infections in hospitalized adult patients. Hospitalized patients who had nasal swab sampling for a suspected viral infection between August 1, 2018 to March 31, 2019 were included. Outcome variables were oxygen requirement, mechanical ventilation need, intensive care unit admission, and cost. At least one viral pathogen was detected in 125 (47.7%) of 262 patients who were included in the study. Fifty-five (20.9%) of the patients were infected with influenza. Influenza-positive patients had higher rates for respiratory support, intensive care unit admission, and mortality compared to all other patients. The average cost of hospitalization per person was 2879.76 USD in the influenza-negative group, while the same cost was 3274.03 USD in the influenza-positive group. Although all of the vaccinated influenza-positive patients needed oxygen support, neither of them required invasive mechanical ventilation or intensive care unit admission. The average hospitalization cost per person was 779.70 USD in the vaccinated group compared to 3762.01 USD in the unvaccinated group. Disease-related direct cost of influenza in the community was estimated as 22 776 075.61 USD in the 18-65 years of age group and 15 756 120.02 USD in the 65 years of age and over group per year. Influenza, compared to other respiratory virus infections, can lead to untoward clinical outcomes and mortality as well as higher direct medical costs in adults.


Assuntos
Influenza Humana , Humanos , Adulto , Idoso , Influenza Humana/prevenção & controle , Estresse Financeiro , Estações do Ano , Hospitalização , Efeitos Psicossociais da Doença , Oxigênio
3.
Lancet ; 398(10296): 213-222, 2021 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-34246358

RESUMO

BACKGROUND: CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey. METHODS: This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18-59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 µg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0·5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting. FINDINGS: Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65·1%] in the vaccine group and 3568 [34·9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65·4%] and 3470 [34·6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36-48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31·7 cases [14·6-59·3] per 1000 person-years) and 32 cases were reported in the placebo group (192·3 cases [135·7-261·1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83·5% (95% CI 65·4-92·1; p<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8·2%] participants in the vaccine group and 248 [7·0%] the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 [2·4%] in the vaccine group and 40 [1·1%] in the placebo group, p<0·0001). INTERPRETATION: CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile. FUNDING: Turkish Health Institutes Association.


Assuntos
Anticorpos Neutralizantes , Vacinas contra COVID-19/uso terapêutico , COVID-19/imunologia , SARS-CoV-2/imunologia , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , COVID-19/prevenção & controle , Método Duplo-Cego , Pessoal de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Turquia , Vacinação , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vírion/imunologia
4.
J Gerontol Nurs ; 48(8): 43-51, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35914081

RESUMO

The current study aimed to screen for delirium in hospitalized older adults and assess the validity of the Turkish version of the 4A's Test (4AT-TR) as a feasible tool to integrate in routine patient care. The point prevalence of delirium according to clinical evaluation in routine practice was detected among all patients aged ≥60 years in 12 pilot wards. Delirium screening was then conducted by two arms: (a) nurses using the 4AT-TR and (b) geriatricians according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria. Prevalence of delirium according to clinical impression was 3.3% (n = 4), whereas prevalence was 12.4% (n = 17) according to DSM-5 criteria and 13.8% (n = 17) according to the 4AT-TR. The 4AT-TR performed by nurses had a sensitivity of 66.6% and specificity of 93.5%. Area under the receiver operating characteristic curve for delirium diagnosis was 0.819 (p < 0.001). Most delirium cases remain undetected unless a routine and formal delirium assessment is integrated in hospital care of high-risk patients. The 4AT-TR performed by nurses seems to be a valid tool for determining delirium in hospitalized older adults. [Journal of Gerontological Nursing, 48(8), 43-51.].


Assuntos
Delírio , Idoso , Delírio/diagnóstico , Delírio/epidemiologia , Humanos , Programas de Rastreamento , Estudos Prospectivos , Melhoria de Qualidade
5.
Mikrobiyol Bul ; 56(3): 553-565, 2022 Jul.
Artigo em Turco | MEDLINE | ID: mdl-35960245

RESUMO

The coronavirus disease-2019 (COVID-19) has become a global cause of death/injury, particularly for those with limited access to vaccination programs and healthcare systems. The risk of re-infection is not negligible due to the emergence of new variants and the decrease in immunity of those who have recovered COVID-19 before. In this study, it was aimed to show longitudinally the change in antibody levels of patients hospitalized for COVID-19 who had an antibody response in the early stages of their infection and to reveal a response pattern that would help to predict patients whose antibody responses decreased or persisted over time. This observational, single-center study included 38 non-critical patients admitted to COVID-19 wards. Anti-spike-1 IgG levels were investigated by the "enzyme-linked immunosorbent assay (ELISA)" method in two different samples taken at different times in each patient. Two distinct anti-spike-1 IgG antibody response patterns were detected in the study; the first pattern was that with low antibody production at first who had an increase in antibody levels after an average of six months, and the second pattern was that the initially high antibody levels decreased after an average of six months. This paradoxical kinetic may blur physicians' predictions of antibody response. In general, anti-spike-1 antibody levels showed a moderate decrease after six months, but production seems to continue (mean ∆IgG= -0.77; σ= 4; p= 0.24). Higher antibody levels were observed at the beginning in patients with concomitant bacterial pneumonia (mean initial IgG= 7.67; σ= 3.54) (p= 0.03). Although the production of S1-IgG in patients recovered from severe acute respiratory system coronavirus2 (SARS-CoV-2) was modestly reduced compared to the beginning measurements, the production in general persisted during the study period. It appears that IgG responses increase or remain constant in individuals with relatively low IgG index values when controlled after an average of 180 days, while IgG tends to decrease in individuals with high IgG index values.


Assuntos
COVID-19 , Anticorpos Antivirais , Formação de Anticorpos , Humanos , Imunoglobulina G , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
6.
Turk J Med Sci ; 52(3): 580-586, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36326303

RESUMO

BACKGROUND: Bordetella pertussis infection remains an important health problem in adults due to the increasing prevalence in recent years. Pertussis in adults can be easily overlooked or misdiagnosed. We aimed to determine the prevalence of pertussis in adult patients with acute cough and the clinical features of the pertussis cases. METHODS: Internal Medicine and Pulmonology inpatient wards and outpatient clinics were screened between March 2017 and June 2018. Patients with cough duration between 1 week and 1 month were enrolled. Those who were on antibiotics for more than 5 days were excluded. A total of 115 patients were enrolled. Nasopharyngeal swabs were taken and real-time polymerase chain reaction analyses were done. RESULTS: According to the pertussis case definition, 47.8% of the patients were diagnosed with probable pertussis. We found the prevalence of pertussis as 3.5% in our cohort. All of the patients with pertussis had a history of paroxysmal cough with a mean duration of 20 days. DISCUSSION: These results show that pertussis continues to be a health problem for adults and may present with acute cough. The growing number of adult pertussis cases suggest that vaccination of children is inadequate to prevent pertussis and the concept of 'lifelong vaccination' should be strengthened.


Assuntos
Coqueluche , Criança , Adulto , Humanos , Coqueluche/complicações , Coqueluche/epidemiologia , Coqueluche/diagnóstico , Tosse/epidemiologia , Prevalência , Bordetella pertussis/genética , Reação em Cadeia da Polimerase em Tempo Real
7.
Turk J Med Sci ; 52(1): 1-10, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34493032

RESUMO

BACKGROUND: We aimed to analyze the usefulness of such a reserved area for the admission of the patients' symptoms suggesting COVID-19 and compare the demographic and clinical characteristics of the patients with COVID-19 and without COVID-19 who were admitted to C1 during the first month of the COVID-19 outbreak in our hospital. METHODS: A new area was set up in Hacettepe University Adult Hospital to limit the contact of COVID-19 suspicious patients with other patients, which was named as COVID-19 First Evaluation Outpatient Clinic (C1). C1 had eight isolation rooms and two sampling rooms for SARS-CoV-2 polymerase-chain-reaction (PCR). All rooms were negative-pressurized. Patients who had symptoms that were compatible with COVID-19 were referred to C1 from pretriage areas. All staff received training for the appropriate use of personal protective equipment and were visited daily by the Infection Prevention and Control team. RESULTS: One hundred and ninety-eight (29.4%) of 673 patients who were admitted to C1were diagnosed with COVID-19 between March 20, 2020, and April 19, 2020. SARS-CoV-2 PCR was positive in 142 out of 673 patients. Chest computerized tomography (CT) was performed in 421 patients and COVID-19 was diagnosed in 56 of them based on CT findings despite negative PCR. Four hundred and ninety-three patients were tested for other viral and bacterial infections with multiplex real-time reverse-transcriptase PCR (RTPCR). Blood tests that included complete blood count, renal and liver functions, d-dimer levels, ferritin, C- reactive protein, and procalcitonin were performed in 593 patients. Only one out of 44 healthcare workers who worked at C1 was infected by SARS-CoV-2. DISCUSSION: Early diagnosis of infected patients and ensuring adequate isolation are very important to control the spread of COVID-19. The purpose of setting up the COVID-19 first evaluation outpatient clinic was to prevent the overcrowding of ER due to mild or moderate infections, ensure appropriate distancing and isolation, and enable emergency services to serve for real emergencies. A wellplanned outpatient care area and teamwork including internal medicine, microbiology, and radiology specialists under the supervision of infectious diseases specialists allowed adequate management of the mild-to-moderate patients with suspicion of COVID-19.


Assuntos
COVID-19 , Adulto , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Turquia/epidemiologia , Hospitais Universitários , Instituições de Assistência Ambulatorial
8.
Mol Cell Biochem ; 476(5): 2075-2084, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33515382

RESUMO

Breast cancer is a highly heterogeneous group of human cancer with distinct genetic, biological and clinicopathological features. Triple-negative breast cancer (TNBC) is the most aggressive and metastatic type of breast cancer and associated with poor patient survival. However, the role of UV Radiation Resistance-Associated Gene (UVRAG) in TNBC remains unknown. Here, we report that UVRAG is highly upregulated in all TNBC cells and its knockdown leads to the inhibition of cell proliferation, colony formation and progression of cell cycle, which is associated with and reduced expression of cell cycle related protein expression, including Cyclin A2, B1, D1, cdc2 and cdk6 in TNBC cells. Inhibition of UVRAG also suppressed cell motility, migration and invasion of TNBC cells by inhibition of Integrin ß1 and ß3 and Src activity. Our findings suggest for the first time that UVRAG expression contributes to proliferation, cell cycle progression, motility/migration and invasion of TNBC cells. Thus, targeting UVRAG could be a potential strategy in breast cancer especially against TNBC.


Assuntos
Movimento Celular , Proliferação de Células , Quinases Ciclina-Dependentes/metabolismo , Integrina beta1/metabolismo , Integrina beta3/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Transdução de Sinais , Proteínas Supressoras de Tumor/metabolismo , Quinases Ciclina-Dependentes/genética , Feminino , Humanos , Integrina beta1/genética , Integrina beta3/genética , Células MCF-7 , Invasividade Neoplásica , Proteínas Proto-Oncogênicas pp60(c-src)/genética , Proteínas Supressoras de Tumor/genética
9.
Intern Med J ; 51(11): 1940-1945, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34796627

RESUMO

The COVID-19 pandemic has increased anxiety in society and particularly in healthcare workers, as shown with a questionnaire in our centre at the beginning of the pandemic. In this collaborative study, we aimed to evaluate the effects of the pandemic on anxiety 1 year later by applying the same questionnaire to the physicians working in the same department. A total of 77 participants consented to the study. The median age was 28 (interquartile range = 4) years and 55.8% were male. As in the first survey, female gender, having family members over 65 years of age, and having family members with chronic diseases were significantly associated with high anxiety scores and levels. There were no statistically significant differences between the first and second survey participants in any of the anxiety scales, which means anxiety persists.


Assuntos
COVID-19 , Médicos , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Pré-Escolar , Estudos Transversais , Depressão , Feminino , Humanos , Medicina Interna , Masculino , Pandemias , SARS-CoV-2
10.
Int J Clin Pract ; 75(12): e14988, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34674358

RESUMO

AIMS: It is evident that the COVID-19 pandemic has affected the medical practice and training of residents. In this study, we evaluated the physical examination (PE) habits of residents working in a university hospital and how their PE practices did change during the pandemic. METHODS: This single-centre, non-interventional, cross-sectional descriptive study was conducted in a university hospital using an online survey questionnaire between 5 and 20 October 2020. RESULTS: Of the 308 residents who participated in the study, 172 of them (55.8%) were female and the median age was 27 (IQR (3) = Q1 (29)-Q3 (26)). Amongst all, 263 participants (85.4%) declared that they have worked in the areas where suspected/confirmed COVID-19 patients were being served. A total of 262 (85%) residents stated that PE habits have changed generally during the pandemic. There was a significant difference with regards to the change in PE habits between those residents who have worked in the COVID-19 areas (n = 230, 87.5%) and those who have not (n = 32, 71.1%) (P = .004). PE habits of Internal Medicine Residents were changed more than others (P < .001). The main reason for the change in PE habits in general (77.9%) and during the examination of suspected/confirmed COVID-19 patients (89.7%) were "self-protection." Independent factors for limited PE in suspected/confirmed COVID-19 patients were found as "Avoiding performing physical examination to be exposed less/to protect (adjusted ORs = 13.067)," "relying on laboratory and radiological investigations during practice (adjusted ORs = 4.358)," and "not having a thought that reduced physical examination will render the diagnosis and course of COVID-19 (adjusted ORs = 2.244)." CONCLUSIONS: This study clearly demonstrated that the COVID-19 pandemic has had a serious impact on the PE habits of the residents while examining patients in general and with COVID-19.


Assuntos
COVID-19 , Pandemias , Adulto , Estudos Transversais , Feminino , Hábitos , Hospitais Universitários , Humanos , Exame Físico , SARS-CoV-2 , Inquéritos e Questionários
11.
Int J Qual Health Care ; 33(3)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34270730

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is a prevalent complication of inpatient care, causing high burden of morbidity and mortality. Prophylaxis reduces the events; thus, these practices are promoted. We aimed to assess the VTE prophylaxis practices in the general internal medicine wards of a tertiary-care university hospital and utilize these data to propose quality improvement projects. OBJECTIVE: Assess the pharmacological venous thromboembolism prophylaxis utilization by using the Padua Prediction Score and demonstrate the main determinants of inappropriate prophylaxis use. METHODS: Electronic medical records were used to collect data cross-sectionally from 1 January 2019 to 30 June 2019. Padua Prediction Score was used to assess the appropriateness of VTE prophylaxis. Underlying health conditions, hospitalization causes, anti-platelets and use of glucocorticoids were also assessed as confounding factors. RESULTS: A total of 295 patients were included. Higher proportion of patients who received VTE prophylaxis were obese and had higher rates of diabetes and coronary artery disease. Prophylaxis was more commonly utilized among patients who were elderly, obese, having an acute infection and/or rheumatologic disorder and prolonged bed rest (P ≤ 0.001, P = 0.01, P = 0.22 and P ≤ 0.001, respectively). Thirty-five patients (11.8%) received VTE prophylaxis, despite 89 patients (30.2%) were high-risk patients. In the high-risk group (n = 89), 27 patients (30.3%) received appropriate pharmacological prophylaxis, while 8 patients (3.9%) received VTE prophylaxis in the low-risk group (total n = 206). A considerable percentage of the high-risk population (69.6%) did not receive VTE prophylaxis. DISCUSSION: Underuse constitutes a major challenge in our hospital but differing from other institutions, overuse is not a significant issue. Further studies are needed whether VTE prophylaxis improvement implementations uniformly increase appropriate VTE use.


Assuntos
Tromboembolia Venosa , Idoso , Anticoagulantes/uso terapêutico , Hospitalização , Hospitais Universitários , Humanos , Pacientes Internados , Fatores de Risco , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/prevenção & controle
12.
Int J Qual Health Care ; 33(1)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33104780

RESUMO

BACKGROUND: The 30-day readmission rate is an important indicator of patient safety and hospital's quality performance. In this study, we aimed to find out the 30-day readmission rate of mild and moderate severity coronavirus disease of 2019 (COVID-19) patients discharged from a tertiary care university hospital and to demonstrate the possible factors associated with readmission. METHODS: This is an observational, single-center study. Epidemiological and clinical data of patients who were hospitalized with a diagnosis of COVID-19 were retrieved from a research database where patient information was recorded prospectively. Readmission data were sought from the hospital information management system and the National Health Information System to detect if the patients were readmitted to any hospital within 30 days of discharge. Adult patients (≥18 years old) hospitalized in COVID-19 wards with a diagnosis of mild or moderate COVID-19 between 20 March 2020 (when the first case was admitted to our hospital) and 26 April 2020 were included. RESULTS: From 26 March to 1 May, there were 154 mild or moderate severity (non-critical) COVID-19 patients discharged from COVID-19 wards, of which 11 (7.1%) were readmitted. The median time of readmission was 8.1 days (interquartile range [IQR] = 5.2). Two patients (18.1%) were categorized to have mild disease and the remaining 9 (81.9%) as moderate disease. Two patients who were over 65 years of age and had metastatic cancers and hypertension developed sepsis and died in the hospital during the readmission episode. Malignancy (18.7% vs. 2.1%, P = 0.04) and hypertension (45.5% vs. 14%, P = 0.02) were more common in those who were readmitted. CONCLUSIONS: This is one of the first studies to report on 30-day readmission rate of COVID-19 in the literature. More comprehensive studies are needed to reveal the causes and predictors of COVID-19 readmissions.


Assuntos
COVID-19/epidemiologia , Readmissão do Paciente/estatística & dados numéricos , Adulto , Idoso , COVID-19/mortalidade , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Indicadores de Qualidade em Assistência à Saúde , SARS-CoV-2 , Atenção Terciária à Saúde , Turquia/epidemiologia
13.
Tuberk Toraks ; 69(2): 237-241, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34256514

RESUMO

Nocardia species are opportunistic bacteria that are frequently contagious by inhalation. Recently, Nocardia abscessus has been described as a different species. We report a 54-year-old male who presented with acute pleuritic chest pain, mimicking pulmonary thromboembolism on the 5th day of discharge from the hospital. The patient was receiving immunosuppressive therapy for newly diagnosed atypical anti-glomerular basement membrane disease. Thorax computed tomography revealed a 17x19 mm soft tissue lesion in the lateral segment of the middle lobe of the right lung. After further examinations, a biopsy decision was made and Nocardia abscessus was isolated in the aerobic culture of the aspiration material.


Assuntos
Glomerulonefrite/complicações , Nocardiose/diagnóstico , Embolia Pulmonar/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Nocardia/isolamento & purificação , Nocardiose/diagnóstico por imagem , Nocardiose/microbiologia , Embolia Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X
14.
Br J Cancer ; 122(8): 1146-1157, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32115576

RESUMO

BACKGROUND: Dysregulation of the metabolome is a hallmark of primary brain malignancies. In this work we examined whether metabolic reprogramming through a multi-targeting approach causes enhanced anti-cancer activity in glioblastoma. METHODS: Preclinical testing of a combined treatment with ONC201/TIC10 and 2-Deoxyglucose was performed in established and primary-cultured glioblastoma cells. Extracellular flux analysis was used to determine real-time effects on OXPHOS and glycolysis. Respiratory chain complexes were analysed by western blotting. Biological effects on tumour formation were tested on the chorioallantoic membrane (CAM). RESULTS: ONC201/TIC10 impairs mitochondrial respiration accompanied by an increase of glycolysis. When combined with 2-Deoxyglucose, ONC201/TIC10 induces a state of energy depletion as outlined by a significant decrease in ATP levels and a hypo-phosphorylative state. As a result, synergistic anti-proliferative and anti-migratory effects were observed among a broad panel of different glioblastoma cells. In addition, this combinatorial approach significantly impaired tumour formation on the CAM. CONCLUSION: Treatment with ONC201/TIC10 and 2-Deoxyglucose results in a dual metabolic reprogramming of glioblastoma cells resulting in a synergistic anti-neoplastic activity. Given, that both agents penetrate the blood-brain barrier and have been used in clinical trials with a good safety profile warrants further clinical evaluation of this therapeutic strategy.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Desoxiglucose/farmacologia , Metabolismo Energético/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Imidazóis/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Embrião de Galinha/efeitos dos fármacos , Glioblastoma/metabolismo , Glioblastoma/patologia , Glicólise/efeitos dos fármacos , Humanos , Fosforilação Oxidativa
15.
Intern Med J ; 50(11): 1350-1358, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33006419

RESUMO

BACKGROUND: Internists who have an important role in the global response to the COVID-19 pandemic are under both physical and psychological pressures. AIMS: To assess the anxiety among physicians working in the internal medicine department of a tertiary care hospital who are on the frontline of the COVID-19 pandemic. METHODS: This single-centre, non-intervention, cross-sectional descriptive study was conducted using an online survey questionnaire from 1 April to 14 April 2020. Physicians of the Department of Internal Medicine were invited to participate with a self-administered questionnaire. The degree of symptoms of anxiety was assessed by the Turkish versions of the 7-item Generalised Anxiety Disorder scale and Beck Anxiety Inventory, respectively. RESULTS: A total of 113 participants consented for the study and completed the questionnaire. The median age was 29 (IQR = 5) years and 53.1% were male. A total of 72 internists (63.7%) worked as 'frontline' healthcare workers directly engaged in diagnosing, treating or caring for patients with or suspected to have COVID-19. Female gender was significantly associated with high scores and levels in all scales compared to the male gender (P < 0.005). Having family members over 65 years old and with chronic diseases were significantly associated with high anxiety scores and levels (P < 0.005). CONCLUSIONS: In this survey of internists in a university hospital equipped with clinics, wards and intensive care unit for patients with COVID-19, female gender and having family members over 65 years old and with chronic diseases were associated with increased anxiety levels.


Assuntos
Ansiedade/etiologia , COVID-19/psicologia , Saúde Mental , Médicos/psicologia , Adulto , Transtornos de Ansiedade , Estudos Transversais , Família , Feminino , Humanos , Medicina Interna , Masculino , Fatores Sexuais , Estresse Psicológico , Inquéritos e Questionários , Centros de Atenção Terciária , Turquia
16.
Tuberk Toraks ; 68(4): 388-398, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33448736

RESUMO

INTRODUCTION: Respiratory virus infections may cause serious respiratory failure requiring intensive care unit (ICU) admission. The objective of this study was to evaluate the clinical features and the outcome in patients with acute respiratory failure (ARF) due to viral infections comparing etiological agents. MATERIALS AND METHODS: ARF patients with positive viral serology were retrospectively recruited. Cohort was evaluated with regard to subgroups as influenza and other respiratory viruses (ORV), as well as survivors and nonsurvivors. RESULT: Out of 938 admitted patients, 319 were followed as ARF and only 149 patients had viral respiratory panel results. In 49 patients with ARF, 52 positive viral results were detected and 47 patients with single positive viral isolates of either influenza or ORV were included. Among them, 62% had ORV with quite similar characteristics with influenza group apart from diabetes mellitus which was encountered more in influenza group (p= 0.02). Overall ICU mortality was 32% and there was no difference between the two groups (p= 0.42). Acute Physiology and Chronic Health Evaluation (APACHE) II score was independently associated with ICU mortality (OR: 1.25; 95% CI: 1.04-1.51; p= 0.02). CONCLUSIONS: This study emphasizes to consider the possibility of other respiratory viruses for the cause of ARF with similar characteristics and mortality as influenza species.


Assuntos
Estado Terminal , Influenza Humana/mortalidade , Admissão do Paciente , Síndrome do Desconforto Respiratório/mortalidade , APACHE , Adulto , Idoso , Estudos de Coortes , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Turquia , Adulto Jovem
18.
Med Sci Monit ; 23: 3178-3184, 2017 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-28662014

RESUMO

BACKGROUND Immunization is one of the most effective public health measures to prevent disease, but vaccination rates in adult populations still remain below the targets. Patient and physician attitudes about vaccination are important for adult vaccination. In this study, we aimed to determine patient attitudes and perceptions about vaccination and the vaccination coverage rates of adult patients in a university hospital in Turkey. MATERIAL AND METHODS A survey was conducted between October 2014 and May 2015 at the Internal Medicine Outpatient Clinics of a university hospital. Adult patients were asked to fill out a questionnaire on their perceptions and attitudes about vaccination and their vaccination status. RESULTS We interviewed 512 patients ages 19-64 years. Eighty percent of the study population thought that adults should be vaccinated, while only 36.1% of the patients stated that vaccination was ever recommended to them in their adult life. Forty-eight percent of the patients stated that they were vaccinated at least once in their adulthood. The most commonly received vaccine was tetanus vaccine in general, while influenza vaccine was the leading vaccine among patients with chronic medical conditions. While 71.4% of the patients to whom vaccination was recommended received the vaccine, 34.9% of the patients received a vaccine without any recommendation. CONCLUSIONS Although the vaccine coverage rates among adults in this survey were low, the perceptions of patients about adult vaccination were mainly positive and of many of them positively reacted when their physician recommended a vaccine.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Percepção , Vacinação , Adulto , Comorbidade , Demografia , Feminino , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Vacinas/imunologia , Adulto Jovem
19.
Mikrobiyol Bul ; 51(1): 20-31, 2017 Jan.
Artigo em Turco | MEDLINE | ID: mdl-28283007

RESUMO

The knowledge about the viral etiologies causing respiratory disease in adults is limited. Viral respiratory diseases may lead deterioration in certain patient populations. The aim of this study was to determine the viral etiologies of influenza-like illness among patients requiring hospitalization and to document the risk factors for mortality. This prospective study was performed in one of the 7 centers in Turkey in the context of influenza surveillance by the Global Influenza Hospital Surveillance Network. A 35-bed Adult Emergency Service and 10-bed Acute Care Unit were screened for consequent recruitment of eligible patients daily, on weekdays only. ICD-10 codes in the electronic health records and direct patient encounters were used to screen for the following eligibility diagnoses: acute respiratory tract infection, asthma, heart failure, pneumonia, influenza, chronic obstructive lung disease, dyspnea/respiratory abnormality, respiratory symptoms, cough and fever. A total of 334 patients who were admitted with the eligible ICD-10 codes within the 24th and 48th hours were screened during the study period and of those eligible ones, 106 consented and were swabbed. Nasal or nasopharyngeal swabs were collected using Virocult (Medical Wire & Equipment, UK) and sent to the central laboratory in 1-3 days. Swabs were collected and specimens were introduced to real-time polymerase chain reaction based multiplex kits, as well as, ABI 7500 platform with CDC primers and probes. A total of 106 patients were swabbed. Hospital mortality was 12.2%. More than one fourth of the patients needed a sort of mechanical ventilation support and at least one organ failure developed in one third of the patients. One or more viral pathogens were detected in 56 (52.8%) of the swabbed patients, with influenza H3N2 being the most prevalent one. Having a lower body mass index (OR, 0.845, p= 0.034) was associated with mortality. Chronic lung diseases were shown to confer a survival advantage (OR, 0.127, p= 0.009). Community acquired viral respiratory infections might lead to significant compromise in adult patients. Prevention of malnutrition might result in better outcomes in patients who need acute admission. The survival advantage of those with chronic lung diseases warrants further investigation.


Assuntos
Hospitalização/estatística & dados numéricos , Influenza Humana/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Nariz/virologia , Estudos Prospectivos , Fatores de Risco , Turquia/epidemiologia , Adulto Jovem
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