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2.
Medicine (Baltimore) ; 100(3): e23969, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33545981

RESUMO

ABSTRACT: This study aimed to evaluated the clinical impact of adding [11C] Pittsburgh compound-B (11C-PiB) PET for clinical diagnosis of mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia.Twenty six (mean age 78.5 ±â€Š5.18 years, 21 females) AD (n = 7), amnestic MCI (n = 12), non-amnestic MCI (n = 3), vascular dementia, progressive supranuclear palsy (PSP) with frontotemporal dementia (FTD), FTD (n = 1 each), and normal (n = 1) patients underwent 11C-PiB-PET, MRI, and SPECT scanning. 11C-PiB-PET was compared with MRI and SPECT for clinical impact.11C-PiB-PET showed positivity in 6, 9, and 0 of the AD, amnestic MCI, and non-amnestic MCI patients, respectively, and 0 of those with another disease. Parahippocampal atrophy at VSASD was observed in 5 AD patients, 6 amnestic and PiB-positive MCI patients, 1 amnestic and PiB-negative MCI patient, and 1 vascular dementia patient. Parietal lobe hypoperfusion in SPECT findings was observed in 6, 4, and 2 of those, respectively, as well as 1 each of non-amnestic MCI, vascular dementia, and normal cases. Sensitivity/specificity/accuracy for selecting PiB-positive patients among the 15 MCI patients for 11C-PiB-PET were 100% (9/9)/100% (6/6)/100% (15/15), for VSRAD were 66.7% (6/9)/83.3% (5/6)/73.3% (11/15), and for SPECT were 44.4% (4/9)/50.0% (3/6)/46.7% (7/15), while those were 88.9% (8/9)/33.3% (2/6)/66.7% (10/15)/for combined VSRAD and SPECT. 11C-PiB-PET accuracy was significantly higher than that of SPECT.11PiB-PET alone may be useful for selecting patients who will progress from MCI to AD in the future, although follow-up study is necessary to clarify the outcome of MCI patients.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/uso terapêutico , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Tiazóis/uso terapêutico , Tomografia Computadorizada de Emissão de Fóton Único/métodos
3.
J Med Microbiol ; 70(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33625354

RESUMO

Introduction. Cryptosporidium parvum causes intestinal parasitic infections affecting both immunosuppressed and immunocompetent individuals.Gap statement. Given the absence of effective treatments for cryptosporidiosis, especially in immunodeficient patients, the present study was designed to assess the therapeutic efficacy of secnidazole (SEC) and its combination with nitazoxanide (NTZ) in comparison to single NTZ treatment in relation to the immune status of a murine model of C. parvum infection.Methodology. The infected groups were administered NTZ, SEC or NTZ-SEC for three or five successive doses. At days 10 and 12 post-infection (p.i.), the mice were sacrificed, and the efficacy of the applied drugs was evaluated by comparing the histopathological alterations in ileum and measuring the T helper Th1 (interferon gamma; IFN-γ), Th2 [interleukin (IL)-4 and IL-10] and Th17 (IL-17) cytokine profiles in serum.Results. The NTZ-SEC combination recorded the maximal reduction of C. parvum oocyst shedding, endogenous stages count and intestinal histopathology, regardless of the immune status of the infected mice. The efficacy of NTZ-SEC was dependent on the period of administration, as the 5 day-based treatment protocol was also more effective than the 3 day-based one in terms of immunocompetence and immunosuppression. The present treatment schedule induced an immunomodulatory effect from SEC that developed a protective immune response against C. parvum infection with reduced production of serum IL-17, IFN-γ, IL-4 and IL-10.Conclusions. Application of NTZ-SEC combined therapy may be useful in treatment of C. parvum, especially in cases involving immunosuppression.


Assuntos
Antiprotozoários/uso terapêutico , Criptosporidiose/tratamento farmacológico , Imunomodulação/efeitos dos fármacos , Metronidazol/análogos & derivados , Nitrocompostos/uso terapêutico , Tiazóis/uso terapêutico , Animais , Criptosporidiose/imunologia , Criptosporidiose/parasitologia , Criptosporidiose/patologia , Cryptosporidium parvum/efeitos dos fármacos , Citocinas/sangue , Modelos Animais de Doenças , Esquema de Medicação , Quimioterapia Combinada , Íleo/efeitos dos fármacos , Íleo/parasitologia , Íleo/patologia , Hospedeiro Imunocomprometido , Masculino , Metronidazol/uso terapêutico , Camundongos , Carga Parasitária
4.
Medicine (Baltimore) ; 100(2): e24094, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466174

RESUMO

INTRODUCTION: Bleeding may interfere with the visual field and create difficulties in performing the intended treatment, especially in operations involving a small working space such as endoscopic spinal surgery. Therefore, it is important to reduce the risk of bleeding before surgery. PATIENT CONCERNS: A 76-year-old female presented with a history of right anterior thigh pain along the L3 dermatome for 3-years, following a L3 compression fracture. In addition, the patient had developed autoimmune hepatitis at 50 years of age, and the platelet count on laboratory blood collection was 78 × 109/L. DIAGNOSIS: Magnetic resonance (MR) images showed a narrowed foramen at the L3-4 level. L3 nerve block was effective. L3 foraminal-stenosis was suspected. INTERVENTIONS: Micro-endoscopic laminectomy (MEL) for foraminal decompression was planned due to possible L3 nerve root compression. Lusutrombopag, a thrombopoietin (TPO) receptor agonist, was orally administered for 7 days starting 7 days preoperatively to address the risks of bleeding. OUTCOMES: The patient successfully underwent MEL without any adverse events or complications. CONCLUSION: The results obtained from the use of lusutrombopag suggested that safety measures could be implemented preoperatively, and that lusutrombopag may be a useful supplemental drug for minimally invasive treatment of patients with cirrhosis and thrombocytopenia.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Cinamatos/uso terapêutico , Endoscopia , Fraturas da Coluna Vertebral/cirurgia , Tiazóis/uso terapêutico , Trombocitopenia/tratamento farmacológico , Idoso , Doença Hepática Terminal/complicações , Feminino , Humanos , Vértebras Lombares/cirurgia , Trombocitopenia/etiologia
5.
Recenti Prog Med ; 112(1): 15-18, 2021 01.
Artigo em Italiano | MEDLINE | ID: mdl-33512353

RESUMO

It was a very dark year for EBM. One of the side effects of the Covid-19 pandemic is a severe compression of the evidences. Here are some worrying events. May 2020: the saga of hydroxychloroquine. October 2020: the nitazoxanide case. November 2020: Trump Administration Interferes on Expert Opinion. December 2020: the results of the trials on the first two vaccines were announced in press releases, leaving many scientific uncertainties. Peter Piot, head of the London School of Hygiene & Tropical Medicine noted that none of the CoViD-19 vaccines have offered much data to date. «It is frustrating that all of these announcements are delivered via press release, and not give us a chance to review the actual data. We desperately need total transparency on evidence and data¼, says Piot. Better now to relaunch the spread of EBM. In the issue, we have included the best EBM-based readings from the Club for Evidence-Based in Gastroenterology & Hepatology (ebgh.it).


Assuntos
Acesso à Informação , Medicina Baseada em Evidências/tendências , Pandemias , Antivirais/uso terapêutico , Brasil , /epidemiologia , Ensaios Clínicos como Assunto , Revelação , Humanos , Hidroxicloroquina/uso terapêutico , Itália , Política , Propaganda , Tiazóis/uso terapêutico , Estados Unidos
6.
BMJ Case Rep ; 14(1)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472803

RESUMO

Granulicatella adiacens, which occurs as part of the oral microflora, is an uncommon cause of infection. However, it can cause serious bloodstream infections including infective endocarditis. Although oral bacteria, most commonly the Fusobacterium spp, can cause internal jugular vein (IJV) thrombophlebitis, there are no reported cases of IJV thrombosis caused by G. adiacens Here we report a patient with septic IJV thrombosis with G. adiacens bacteraemia. A middle-aged man presented to our hospital with fever and altered mental status. Blood cultures were positive for G. adiacens, and pan-scan CT with contrast showed left IJV thrombosis, pulmonary embolism and abscesses in the gluteal muscles. The patient was successfully treated with antibiotics. When confronted with G. adiacens bacteraemia in patients with poor oral hygiene, it is necessary to be cautious of the fact that this organism can cause IJV thrombophlebitis.


Assuntos
Abscesso/diagnóstico por imagem , Carnobacteriaceae , Infecções por Bactérias Gram-Positivas/diagnóstico , Veias Jugulares , Embolia Pulmonar/diagnóstico por imagem , Tromboflebite/diagnóstico por imagem , Abscesso/terapia , Antibacterianos/uso terapêutico , Hemocultura , Nádegas , Drenagem , Duração da Terapia , Inibidores do Fator Xa/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/etiologia , Piridinas/uso terapêutico , Tiazóis/uso terapêutico , Tromboflebite/tratamento farmacológico , Tomografia Computadorizada por Raios X
7.
Ann Palliat Med ; 10(1): 707-720, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33440983

RESUMO

The whole world is battling through coronavirus disease 2019 (COVID-19) which is a fatal pandemic. In the early 2020, the World Health Organization (WHO) declared it as a global health emergency without definitive treatments and preventive approaches. In the absence of definitive therapeutic agents, this thorough review summarizes and outlines the potency and safety of all molecules and therapeutics which may have potential antiviral effects. A number of molecules and therapeutics licensed or being tested for some other conditions were found effective in different in vitro studies as well as in many small sample-sized clinical trials and independent case studies. However, in those clinical trials, there were some limitations which need to be overcome to find the most promising antiviral against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In conclusion, many of above-mentioned antivirals seems to have some therapeutic effects but none of them have been shown to have a strong evidence for their proper recommendation and approval in the treatment of COVID-19. Constantly evolving new evidences, exclusive adult data, language barrier, and type of study (observational, retrospective, small-sized clinical trials, or independent case series) resulted to the several limitations of this review. The need for multicentered, large sample-sized, randomized, placebo-controlled trials on COVID-19 patients to reach a proper conclusion on the most promising antiviral agent is warranted.


Assuntos
Antivirais/uso terapêutico , /terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/farmacologia , Alanina/uso terapêutico , Amidas/farmacologia , Amidas/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Azetidinas/farmacologia , Azetidinas/uso terapêutico , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Combinação de Medicamentos , Humanos , Hidroxicloroquina/farmacologia , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Indóis/farmacologia , Indóis/uso terapêutico , Interferons/farmacologia , Interferons/uso terapêutico , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Lopinavir/farmacologia , Lopinavir/uso terapêutico , Oseltamivir/farmacologia , Oseltamivir/uso terapêutico , Purinas/farmacologia , Purinas/uso terapêutico , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Ribavirina/farmacologia , Ribavirina/uso terapêutico , Ritonavir/farmacologia , Ritonavir/uso terapêutico , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Tiazóis/farmacologia , Tiazóis/uso terapêutico
8.
Am Heart J ; 233: 109-121, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33358690

RESUMO

BACKGROUND: In patients with atrial fibrillation, incomplete adherence to anticoagulants increases risk of stroke. Non-warfarin oral anticoagulants (NOACs) are expensive; we evaluated whether higher copayments are associated with lower NOAC adherence. METHODS: Using a national claims database of commercially-insured patients, we performed a cohort study of patients with atrial fibrillation who newly initiated a NOAC from 2012 to 2018. Patients were stratified into low (<$35), medium ($35-$59), or high (≥$60) copayments and propensity-score weighted based on demographics, insurance characteristics, comorbidities, prior health care utilization, calendar year, and the NOAC received. Follow-up was 1 year, with censoring for switching to a different anticoagulant, undergoing an ablation procedure, disenrolling from the insurance plan, or death. The primary outcome was adherence, measured by proportion of days covered (PDC). Secondary outcomes included NOAC discontinuation (no refill for 30 days after the end of NOAC supply) and switching anticoagulants. We compared PDC using a Kruskal-Wallis test and rates of discontinuation and switching using Cox proportional hazards models. RESULTS: After weighting patients across the 3 copayment groups, the effective sample size was 17,558 patients, with balance across 50 clinical and demographic covariates (standardized differences <0.1). Mean age was 62 years, 29% of patients were female, and apixaban (43%), and rivaroxaban (38%) were the most common NOACs. Higher copayments were associated with lower adherence (P < .001), with a PDC of 0.82 (Interquartile range [IQR] 0.36-0.98) among those with high copayments, 0.85 (IQR 0.41-0.98) among those with medium copayments, and 0.88 (IQR 0.41-0.99) among those with low copayments. Compared to patients with low copayments, patients with high copayments had higher rates of discontinuation (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.08-1.19; P < .001). CONCLUSIONS: Among atrial fibrillation patients newly initiating NOACs, higher copayments in commercial insurance were associated with lower adherence and higher rates of discontinuation in the first year. Policies to lower or limit cost-sharing of important medications may lead to improved adherence and better outcomes among patients receiving NOACs.


Assuntos
Fibrilação Atrial/complicações , Dedutíveis e Cosseguros/economia , Adesão à Medicação/estatística & dados numéricos , Acidente Vascular Cerebral/prevenção & controle , Anticoagulantes/economia , Anticoagulantes/uso terapêutico , Antitrombinas/economia , Antitrombinas/uso terapêutico , Estudos de Coortes , Dabigatrana/economia , Dabigatrana/uso terapêutico , Bases de Dados Factuais/estatística & dados numéricos , Dedutíveis e Cosseguros/estatística & dados numéricos , Custos de Medicamentos , Inibidores do Fator Xa/economia , Inibidores do Fator Xa/uso terapêutico , Feminino , Humanos , Masculino , Medicare Part C/estatística & dados numéricos , Pessoa de Meia-Idade , Pirazóis/economia , Pirazóis/uso terapêutico , Piridinas/economia , Piridinas/uso terapêutico , Piridonas/economia , Piridonas/uso terapêutico , Rivaroxabana/economia , Rivaroxabana/uso terapêutico , Tamanho da Amostra , Acidente Vascular Cerebral/etiologia , Tiazóis/economia , Tiazóis/uso terapêutico , Estados Unidos , Varfarina/economia , Varfarina/uso terapêutico
10.
Eur Rev Med Pharmacol Sci ; 24(23): 12593-12608, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33336780

RESUMO

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly increasing but the medication options are still limited for this perilous disease. The emergent outbreak of COVID-19 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps propagating globally. The present scenario has emphasized the requirement for therapeutic opportunities to relive and overcome this latest pandemic. Despite the fact, the deteriorating developments of COVID-19, there is no drug certified to have considerable effects in the medical treatment for COVID-19 patients. The COVID-19 pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can save the lives of seriously ill patients, and it is shown in a randomized clinical trial by the United Kingdom that it reduced the death rate in COVID-19 patients. The current review recapitulates the existing evidence of possible therapeutic drugs, peptides, humanized antibodies, convulsant plasma, and vaccination that has revealed potential in fighting COVID-19 infections. Many randomized and controlled clinical trials are taking place to further validate these agent's safety and effectiveness in curing COVID-19.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , /tratamento farmacológico , /terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Antiparasitários/uso terapêutico , Canabinoides/uso terapêutico , Cloroquina/uso terapêutico , Inativadores do Complemento/uso terapêutico , Dexametasona/uso terapêutico , Combinação de Medicamentos , Inibidores Enzimáticos/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Indóis/uso terapêutico , Interferons/uso terapêutico , Ivermectina/uso terapêutico , Lopinavir/uso terapêutico , Pirazinas/uso terapêutico , Ritonavir/uso terapêutico , Teicoplanina/uso terapêutico , Tetraciclinas/uso terapêutico , Tiazóis/uso terapêutico
11.
BMC Infect Dis ; 20(1): 862, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213364

RESUMO

BACKGROUND: The speed and reach of the COVID-19 pandemic has created special scenarios to be considered, such as those in where patients who meet criteria for hospitalization due to moderate/severe disease cannot be hospitalized due to economic constraints and saturation of national health systems. The aim of this report is to present an unusual case of a severe COVID-19 patient managed at home in a developing country, and to discuss some of the available guidelines and potential therapeutic options for this type of cases. CASE PRESENTATION: A 60-year-old female seeking medical attention through teleconsultation presents with profound dyspnea, oppressive chest pain, fatigue, episodic hallucinations, and difficulty sleeping, for what she originally sought medical attention at an ER but could not be admitted due to saturation of the health system. A positive PCR test for COVID-19, and a CT scan of the chest showing bilateral consolidations with ground-glass opacities confirmed the diagnosis. The patient was managed at home, with corticosteroids, nitazoxanide and a single dose of 40 mg of subcutaneous enoxaparin. Colchicine was added at the third day of treatment. Standard oxygen therapy through nasal cannula was also recommended. Daily follow-ups were established to monitor for signs of clinical improvement. Two weeks later from the initial consultation the patient presents marked improvement in her symptoms, as well as in her CT scan, which prompted in discontinuation of the medications and the oxygen therapy. CONCLUSIONS: There are several limitations in this report regarding the clinical data and the management, but such limitations do also reflect the state of emergency and the chaos that resides in the health care systems of developing nations. For the ambulatory care of COVID-19 patients, several aspects of disease management may differ from current guidelines and basic requirements may represent a huge challenge to cover. Further research is needed to assist physicians in the daily clinical decision making, to optimize patient outcomes, and to reduce the probability of adverse scenarios of patients with COVID-19 managed in the ambulatory setting.


Assuntos
Assistência Ambulatorial , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Corticosteroides/uso terapêutico , Antiparasitários , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/patologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Enoxaparina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Oxigenoterapia , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , RNA Viral/genética , RNA Viral/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índice de Gravidade de Doença , Telemedicina , Tiazóis/uso terapêutico , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X
12.
J Clin Neurosci ; 79: 30-32, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33070913

RESUMO

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first reported in Wuhan, China in December 2019, and is ongoing pandemic. While a majority of patients with SARS-CoV-2 infection shows asymptomatic or mild disease, hospitalized patients can develop critical condition, such as pneumonia, sepsis, and respiratory failure. Some cases deteriorate into sever systemic disease and multiorgan failure. Many patients of severe COVID-19 show hypercoagulable state and complicate with venous thromboembolism and atrial thrombosis. We herein reported a case of COVID-19 who developed cerebral venous thrombosis (CVT) co-incidence with pulmonary thromboembolism (PTE). A 56-year-old Japanese man was presented with fever and malaise and diagnosed with COVID-19. He was treated with ciclesonide and azithromycin, but his respiratory condition deteriorated. Thus, systemic corticosteroids and favipiravir were initiated and these treatments resulted in afebrile state, improving malaise and respiratory failure. However, he suddenly developed severe headache and vomiting with increased concentration of D-dimer. Brain CT and MRI showed typical images of CVT in the left transvers sinus and CT pulmonary angiography showed PE. Administration of unfractionated heparin followed by edoxaban treatment reduced the levels of D-dimer and improved his clinical presentation and thrombosis. Monitoring coagulopathy is important in COVID-19 patients and in case of venous thromboembolism, including cerebral venous system, appropriate anticoagulant therapy should be initiated.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Trombose Intracraniana/etiologia , Pneumonia Viral/complicações , Trombose Venosa/etiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Heparina/uso terapêutico , Humanos , Trombose Intracraniana/diagnóstico por imagem , Trombose Intracraniana/tratamento farmacológico , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pandemias , Piridinas/uso terapêutico , Tiazóis/uso terapêutico , Tomografia Computadorizada por Raios X , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/tratamento farmacológico
13.
J Infect Dev Ctries ; 14(9): 982-986, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-33031085

RESUMO

INTRODUCTION: Nitazoxanide has shown efficacy in vitro against coronavirus infections (MERS, SARS, SARS-CoV-2). The aim of this report is to describe the results of treating COVID-19 positive patients with nitazoxanide in three clinical settings: pregnancy/puerperium, hospitalized patients in an Internal Medicine Service and in an ambulatory setting. METHODOLOGY: This was a prospective follow-up and report of COVID-19 cases in three different situations, pregnant women, hospitalized patients receiving medical attention in an Internal Medicine Service and ambulatory patients residing in Toluca City, and Mexico City. RESULTS: The experience with a first group of 20 women, pregnant (17) or in immediate puerperium (3) was successful in 18 cases with two unfortunate deaths. The five cases treated in an Internal Medicine service showed a positive outcome with two patients weaned from mechanical ventilation. Of the remaining 16 patients treated in an ambulatory setting, all got cured. Nitazoxanide seems to be useful against SARS-CoV-2, not only in an early intervention but also in critical condition as well as in pregnancy without undesired effects for the babies. As an adjunctive therapy budesonide was used that seems to contribute to the clinical improvement. CONCLUSIONS: Nitazoxanide could be useful against COVID-19 as a safe and available regimen to be tested in a massive way immediately.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Tiazóis/uso terapêutico , Adulto , Assistência Ambulatorial , Infecções por Coronavirus/mortalidade , Feminino , Seguimentos , Hospitalização , Humanos , Masculino , México/epidemiologia , Pandemias , Pneumonia Viral/mortalidade , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/mortalidade , Estudos Prospectivos , Resultado do Tratamento
15.
Am J Trop Med Hyg ; 103(4): 1397-1404, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32783799

RESUMO

Recurrent enteric infections and micronutrient deficiencies, including deficiencies in the tryptophan-kynurenine-niacin pathway, have been associated with environmental enteric dysfunction, potentially contributing to poor child growth and development. We are conducting a randomized, placebo-controlled, 2 × 2 factorial interventional trial in a rural population in Haydom, Tanzania, to determine the effect of 1) antimicrobials (azithromycin and nitazoxanide) and/or 2) nicotinamide, a niacin vitamer, on attained length at 18 months. Mother/infant dyads were enrolled within 14 days of the infant's birth from September 2017 to September 2018, with the follow-up to be completed in February 2020. Here, we describe the baseline characteristics of the study cohort, risk factors for low enrollment weight, and neonatal adverse events (AEs). Risk factors for a low enrollment weight included being a firstborn child (-0.54 difference in weight-for-age z-score [WAZ] versus other children, 95% CI: -0.71, -0.37), lower socioeconomic status (-0.28, 95% CI: -0.43, -0.12 difference in WAZ), and birth during the preharvest season (November to March) (-0.22, 95% CI: -0.33, -0.11 difference in WAZ). The most common neonatal serious AEs were respiratory tract infections and neonatal sepsis (2.2 and 1.4 events per 100 child-months, respectively). The study cohort represents a high-risk population for whom interventions to improve child growth and development are urgently needed. Further analyses are needed to understand the persistent impacts of seasonal malnutrition and the interactions between seasonality, socioeconomic status, and the study interventions.


Assuntos
Saúde da Criança/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Adulto , Azitromicina/uso terapêutico , Peso Corporal , Transtornos da Nutrição Infantil , Pré-Escolar , Estudos de Coortes , Intervenção Médica Precoce , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Sepse Neonatal/tratamento farmacológico , Sepse Neonatal/epidemiologia , Niacinamida/uso terapêutico , Pobreza , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologia , População Rural , Estações do Ano , Tanzânia/epidemiologia , Tiazóis/uso terapêutico , Adulto Jovem
17.
Protein Cell ; 11(10): 723-739, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32754890

RESUMO

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC50 of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.


Assuntos
Antivirais/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Oxirredutases/antagonistas & inibidores , Pandemias , Pneumonia Viral/tratamento farmacológico , Vírus de RNA/efeitos dos fármacos , Tiazóis/farmacologia , Animais , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Sítios de Ligação/efeitos dos fármacos , Linhagem Celular , Infecções por Coronavirus/virologia , Crotonatos/farmacologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Técnicas de Inativação de Genes , Humanos , Vírus da Influenza A/efeitos dos fármacos , Leflunomida/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/tratamento farmacológico , Oseltamivir/uso terapêutico , Oxirredutases/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Pneumonia Viral/virologia , Ligação Proteica/efeitos dos fármacos , Pirimidinas/biossíntese , Vírus de RNA/fisiologia , Relação Estrutura-Atividade , Tiazóis/uso terapêutico , Toluidinas/farmacologia , Ubiquinona/metabolismo , Replicação Viral/efeitos dos fármacos
18.
Life Sci ; 258: 118179, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32758626

RESUMO

OBJECTIVE: To evaluate whether approved gastroprokinetic agent, acotiamide exerts a direct excitatory effect on bladder to help explain the reported meaningful reduction of post-void residual urine volume (PVR) in detrusor underactivity (DU) patients after thrice daily oral intake of acotiamide 100 mg for 2 weeks. METHODS: Effect of acotiamide [1-16 µM] was assessed on nerve-mediated contractions evoked by electrical field stimulation (EFS) for 5 s with 5 ms pulse trains of 10 V in longitudinal, mucosa intact rat and human bladder strips to construct frequency response curve (1-32 Hz) and repeat 10 Hz stimulation at 60s interval. Effect of acotiamide 2 µM on spontaneous and carbachol evoked contractions was also assessed. RESULTS: Acotiamide 2 µM significantly enhanced the Atropine and Tetrodotoxin (TTX)-sensitive EFS evoked contractions of rat and human bladder at 8-32 Hz (Two-way ANOVA followed Sidak's multiple comparison; *p < 0.01) and on repeat 10 Hz stimulation (Paired Student's t-test; *p < 0.05), while producing a modest effect on the spontaneous contractions and a negligible effect on the carbachol evoked contractions. CONCLUSIONS: Enhancement of TTX-sensitive evoked contractions of rat and human bladder by acotiamide is consistent with the enhancement of excitatory neuro-effector transmission mainly through prejunctional mechanisms. Findings highlight immense therapeutic potential of antimuscarinics with low M3 receptor affinity like acotiamide in Underactive bladder (UAB)/DU treatment.


Assuntos
Benzamidas/uso terapêutico , Tiazóis/uso terapêutico , Bexiga Inativa/tratamento farmacológico , Bexiga Urinária/patologia , Animais , Benzamidas/química , Benzamidas/farmacologia , Carbacol/farmacologia , Estimulação Elétrica , Humanos , Masculino , Contração Muscular/efeitos dos fármacos , Ratos Sprague-Dawley , Tiazóis/química , Tiazóis/farmacologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/inervação
19.
Arch. esp. urol. (Ed. impr.) ; 73(6): 509-522, jul.-ago. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-195926

RESUMO

OBJETIVO: Evaluar si la menor tasa de abandonos del tratamiento de la vejiga hiperactiva (VH) con mirabegrón podría generar ahorros para el Sistema Nacional de Salud (SNS) y ganancia de años de vida ajustados por calidad (AVACs), en comparación con los fármacos antimuscarínicos (AM) (tolterodina, fesoterodina, oxibutinina, solifenacina). MÉTODOS: Modelo probabilístico (simulación de Monte Carlo de segundo orden) en una cohorte hipotética de 1.000 pacientes con VH y un horizonte temporal de 1 año. Las tasas de abandono/persistencia del tratamiento con mirabegrón y AM se obtuvieron de un estudio observacional español en 1.798 pacientes. Los costes unitarios (€ 2018) y la pérdida de utilidades ligada al abandono del tratamiento se obtuvieron de precios públicos españoles y de la literatura, respectivamente. RESULTADOS: En cada paciente tratado con mirabegrón se duplica la tasa de persistencia en comparación con los AM, ganándose anualmente 0,0151 ±0,0007 AVACs, frente a AM. Con mirabegrón se generaría un ahorro anual por paciente de 80,74 ± 4,61 € en comparación con los AM, con una probabilidad de ahorro del 100%. La sustitución hipotética de los AM por mirabegrón, generaría en el plazo de 1 año un ahorro para el SNS de 6,6 millones de euros (IC 95%3,9-10,1 millones de euros) y se ganarían 1.238 AVAC (IC95% 731; 1.885 AVAC). CONCLUSIONES: El modelo probabilístico muestra una mayor persistencia en pacientes tratados con mirabegrón en comparación con los AM, generando un impacto positivo sobre la calidad de vida de los pacientes así como ahorros para el SNS


OBJECTIVE: To evaluate whether the lower dropout rate of the treatment of overactive bladder (OAB) with mirabegron could generate cost savings to the National Health System (NHS) and lead to quality-adjusted life years (QALYs) gains, compared to the most commonly prescribed antimuscarinics (AM) in Spain (tolterodine, fesoterodine, oxybutynin, solifenacin). METHODS: A probabilistic model (second order Monte Carlo simulation) in a hypothetical cohort of 1,000 patients with OAB and a time horizon of 1 year was carried out. Discontinuation and persistence rates for both mirabegron and AM were obtained from a Spanish observational study in 1798 patients. Unit costs (€ 2018) and utility loss associated with treatment discontinuation were obtained from Spanish public prices and literature, respectively. RESULTS: Persistence rates in patients treated with mirabegron were twice as high compared to AM, leading to a QALY gain of 0.0151 ± 0.0007 per year. Treatment with mirabegron could generate savings of 80.74 ± 4.61 € per patient per year compared to AM, assuming 100% probability of saving. The hypothetical substitution of AM treatment for mirabegron could potentially generate savings of 6.6 million euros (95% CI 3.9-10.1 million euros) to the NHS and 1,238 QALYs gains (CI 95% 731; 1,885 QALYs) within a period of 1 year. CONCLUSIONS: The probabilistic model presented showed a greater persistence in patients treated with mirabegron compared to AM, leading to a positive impact in patients quality of life, as well cost savings to the NHS in Spain


Assuntos
Humanos , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária Hiperativa/economia , Agonistas de Receptores Adrenérgicos beta 3/economia , Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Antagonistas Muscarínicos/economia , Antagonistas Muscarínicos/uso terapêutico , Qualidade de Vida , Método de Monte Carlo , Acetanilidas/economia , Acetanilidas/uso terapêutico , Tiazóis/economia , Tiazóis/uso terapêutico , Recusa do Paciente ao Tratamento , Espanha , Fatores de Tempo
20.
Medicine (Baltimore) ; 99(27): e21025, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629725

RESUMO

BACKGROUND: Given the huge burden of atrial fibrillation (AF) and AF-related stroke in Asia, stroke prevention represents an urgent issue in this region. We herein performed a network meta-analysis to examine the role of non-vitamin K antagonist oral anticoagulants (NOACs) in Asian patients with AF. METHODS: A systematic search of the publications was conducted in PubMed and Embase databases for eligible studies until July 2019. The odds ratios (ORs) and 95% confidence intervals (CIs) were regarded as the effect estimates. The surface under the cumulative ranking area (SUCRA) for the ranking probabilities was calculated. RESULTS: A total of 17 studies were included. For comparisons of NOACs vs warfarin, dabigatran (OR = 0.77, 95% CI 0.68-0.86), rivaroxaban (OR = 0.72, 95% CI 0.65-0.81), apixaban (OR = 0.56, 95% CI 0.49-0.65), but not edoxaban reduced the risk of stroke or systemic embolism, wheres dabigatran (OR = 0.56, 95% CI 0.41-0.76), rivaroxaban (OR = 0.66, 95% CI 0.50-0.86), apixaban (OR = 0.49, 95% CI 0.36-0.66), and edoxaban (OR = 0.34, 95% CI 0.24-0.49) decreased the risk of major bleeding. In reducing the risk of stroke or systemic embolism, apixaban and rivaroxaban ranked the best and second best (SUCRA 0.2% and 31.4%, respectively), followed by dabigatran (50.2%), edoxaban (75.2%), and warfarin (93.0%). In reducing the risk of major bleeding, edoxaban, and apixaban ranked the best and second best (1.5% and 30.8%, respectively), followed by dabigatran (48.4%), rivaroxaban (69.2%), and warfarin (100%). CONCLUSION: NOACs were at least as effective as warfarin, but more safer in Asians with AF. Apixaban was superior to other NOACs for reducing stroke or systemic embolism, while edoxaban showed a better safety profile than other NOACs.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico , Administração Oral , Idoso , Antitrombinas/uso terapêutico , Ásia/epidemiologia , Grupo com Ancestrais do Continente Asiático/etnologia , Efeitos Psicossociais da Doença , Dabigatrana/uso terapêutico , Embolia/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/prevenção & controle , Humanos , Masculino , Metanálise em Rede , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Segurança , Acidente Vascular Cerebral/epidemiologia , Tiazóis/uso terapêutico
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