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1.
Reumatologia ; 58(5): 297-311, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33227082

RESUMO

The aim of this review is to describe the metabolism of calcium in ankylosing spondylitis compared to physiologic conditions, and to present the current evidence on the benefits and disadvantages of calcium supplementation in these patients. A narrative review of the literature was conducted using the PubMed database and a total of 65 articles were selected. Calcium is involved in many physiopathological processes, including inflammation, bone loss and bone formation, all of which occur in ankylosing spondylitis. Many ankylosing spondylitis patients suffer from concomitant osteopenia or osteoporosis, which represent indications for calcium supplementation. Conversely, there are still concerns about the use of calcium salts for the prevention of bone fragility in non-osteoporotic or non-osteopenic patients. In these cases, biologic agents may indirectly normalize calcium dysmetabolism by rebalancing the cytokine milieu, in turn associated with bone remodeling. Calcium supplements may be disadvantageous for entheseal calcifications, but so far there are no clear data confirming that such an association exists.

2.
Nutrients ; 12(11)2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33153126

RESUMO

Liver lipid accumulation is a hallmark of non-alcoholic fatty liver disease (NAFLD), broadly associated with insulin resistance. Inositols (INS) are ubiquitous polyols implied in many physiological functions. They are produced endogenously, are present in many foods and in dietary supplements. Alterations in INS metabolism seems to play a role in diseases involving insulin resistance such as diabetes and polycystic ovary syndrome. Given its role in other metabolic syndromes, the hypothesis of an INS role as a supplement in NAFLD is intriguing. We performed a systematic review of the literature to find preclinical and clinical evidence of INS supplementation efficacy in NAFLD patients. We retrieved 10 studies on animal models assessing Myoinosiol or Pinitol deficiency or supplementation and one human randomized controlled trial (RCT). Overall, INS deficiency was associated with increased fatty liver in animals. Conversely, INS supplementation in animal models of fatty liver reduced hepatic triglycerides and cholesterol accumulation and maintained a normal ultrastructural liver histopathology. In the one included RCT, Pinitol supplementation obtained similar results. Pinitol significantly reduced liver fat, post-prandial triglycerides, AST levels, lipid peroxidation increasing glutathione peroxidase activity. These results, despite being limited, indicate the need for further evaluation of INS in NAFLD in larger clinical trials.

3.
PLoS One ; 15(11): e0242765, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33216817

RESUMO

OBJECTIVE: Through a hospital-based SARS-CoV-2 molecular and serological screening, we evaluated the effectiveness of two months of lockdown and two of surveillance, in Milan, Lombardy, the first to be overwhelmed by COVID-19 pandemics during March-April 2020. METHODS: All subjects presenting at the major hospital of Milan from May-11 to July-5, 2020, underwent a serological screening by chemiluminescent assays. Those admitted were further tested by RT-PCR. RESULTS: The cumulative anti-N IgG seroprevalence in the 2753 subjects analyzed was of 5.1% (95%CI = 4.3%-6.0%), with a peak of 8.4% (6.1%-11.4%) 60-63 days since the peak of diagnoses (March-20). 31/106 (29.2%) anti-N reactive subjects had anti-S1/S2 titers >80 AU/mL. Being tested from May-18 to June-5, or residing in the provinces with higher SARS-CoV-2 circulation, were positively and independently associated with anti-N IgG reactivity (OR [95%CI]: 2.179[1.455-3.264] and 3.127[1.18-8.29], respectively). In the 18 RT-PCR positive, symptomatic subjects, anti-N seroprevalence was 33.3% (95% CI: 14.8%-56.3%). CONCLUSION: SARS-CoV-2 seroprevalence in Milan is low, and in a downward trend after only 60-63 days since the peak of diagnoses. Italian confinement measures were effective, but the risk of contagion remains concrete. In hospital-settings, the performance of molecular and serological screenings upon admission remains highly advisable.


Assuntos
Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Betacoronavirus , Criança , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Imunoglobulina G/sangue , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Estudos Soroepidemiológicos , Adulto Jovem
4.
Molecules ; 25(18)2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899888

RESUMO

N-anilinoethylamides are a class of melatoninergic agents with the aniline portion mimicking the indole ring of the natural ligand and the ethylamide chain reproducing that of melatonin. The simplest compound in this class, N-{2-[(3-methoxyphenyl)methylamino]ethyl}acetamide (UCM793), has nanomolar binding affinity for MT1 and MT2 membrane receptors. To explore the effect of chain conformation on receptor binding, a methyl group was inserted on the methylene alpha or beta to the amide nitrogen and conformational equilibria were investigated by NMR spectroscopy and molecular dynamics simulations. Receptor affinity was conserved only for the beta-methyl derivative, which also showed significant stereoselectivity, with the (S) enantiomer being the eutomer. Molecular dynamics simulations, validated by NMR spectroscopy, showed that the beta-methyl group affects the conformational preferences of the ethylamide chain. Docking into the receptor crystal structure provides a rationale for the observed chiral recognition, suggesting that the (S)-beta-methyl group favors the conformation that better fits the receptor binding site.

5.
Clin Transl Sci ; 13(6): 1071-1076, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32926573

RESUMO

Conflicting evidence regarding the use of hydroxychloroquine (HCQ) and azithromycin for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection do exist. We performed a retrospective single-center cohort study including 377 consecutive patients admitted for pneumonia related to coronavirus disease 2019 (COVID-19). Of these, 297 were in combination treatment, 17 were on HCQ alone, and 63 did not receive either of these 2 drugs because of contraindications. The primary end point was in-hospital death. Mean age was 71.8 ± 13.4 years and 34.2% were women. We recorded 146 deaths: 35 in no treatment, 7 in HCQ treatment group, and 102 in HCQ + azithromycin treatment group (log rank test for Kaplan-Meier curve P < 0.001). At multivariable Cox proportional hazard regression analysis, age (hazard ratio (HR) 1.057, 95% confidence interval (CI) 1.035-1.079, P < 0.001), mechanical ventilation/continuous positive airway pressure (HR 2.726, 95% CI 1.823-4.074, P < 0.001), and C reactive protein above the median (HR 2.191, 95% CI 1.479-3.246, P < 0.001) were directly associated with death, whereas use of HCQ + azithromycin (vs. no treatment; HR 0.265, 95% CI 0.171-0.412, P < 0.001) was inversely associated. In this study, we found a reduced in-hospital mortality in patients treated with a combination of HCQ and azithromycin after adjustment for comorbidities. A large randomized trial is necessary to confirm these findings.


Assuntos
Azitromicina/administração & dosagem , Hidroxicloroquina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
PLoS One ; 15(9): e0236311, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32898153

RESUMO

Since SARS-CoV-2-based disease (COVID-19) spreads as a pandemic, the necessity of a highly sensitive molecular diagnosis that can drastically reduce false negatives reverse transcription PCR (rtPCR) results, raises as a major clinical need. Here we evaluated the performance of a ddPCR-based assay to quantify SARS-CoV-2 titer in 55 suspected COVID-19 cases with negative rtPCR results thanks to in-house ddPCR assay (targeting RdRp and host RNaseP). Samples were collected at ASST-GOM Niguarda between February and May 2020 at hospital admission. Clinical and imaging data were obtained for clinical staging and definition of disease severity. Patients were mainly female (45.5%) with a median age of 73 (57-84) years. ddPCR-based assay detected SARS-CoV-2 genome in nasopharyngeal samples of 19 (34.5%) patients (median viral-load: 128 copies/mL, IQR: 72-345). In 15 of them (78.9%), chest CT showed a classical COVID-19 bilateral interstitial pneumonia; 14 patients (73.7%) showed severe COVID-19 manifestations. ddPCR did not identify any trace of SARS-CoV-2 genome in the respiratory samples of the remaining 36 patients. The serological assay performed in a subgroup of 34 patients at the later stage of illness (from 3 days to 90 days after) confirmed the presence of SARS-CoV-2 antibodies in all patients tested positive for SARS-CoV-2 in ddPCR (100%). Contrariwise, negative tests were observed in 95.0% ddPCR negative patients (P<0.001). Thanks to a ddPCR-based assay, we achieved a rapid and accurate SARS-CoV-2 diagnosis in rtPCR-negative respiratory samples of individuals with COVID-19 suspect, allowing the rapid taking care and correct management of these patients.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Nasofaringe/virologia , Pneumonia Viral/diagnóstico , RNA Viral/análise , Reação em Cadeia da Polimerase em Tempo Real/métodos , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Feminino , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , RNA Viral/metabolismo , Índice de Gravidade de Doença , Carga Viral
7.
Int J Mol Sci ; 21(17)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32883002

RESUMO

Palbociclib, ribociclib, and abemaciclib belong to the third generation of cyclin-dependent kinases inhibitors (CDKis), an established therapeutic class for advanced and metastatic breast cancer. Interindividual variability in the therapeutic response of CDKis has been reported and some individuals may experience increased and unexpected toxicity. This narrative review aims at identifying the factors potentially concurring at this variability for driving the most appropriate and tailored use of CDKis in the clinic. Specifically, concomitant medications, pharmacogenetic profile, and pathophysiological conditions could influence absorption, distribution, metabolism, and elimination pharmacokinetics. A personalized therapeutic approach taking into consideration all factors potentially contributing to an altered pharmacokinetic/pharmacodynamic profile could better drive safe and effective clinical use.

8.
Ann Med ; 52(7): 413-422, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32795156

RESUMO

INTRODUCTION: Clinical and pharmacological characteristics of elderly patients hospitalized for bleeding and in-hospital mortality according to bleeding type are barely described. METHODS: Retrospective cohort study of 13,496 consecutive patients admitted to internal medicine wards. Clinical characteristics, comorbidities and pharmacological treatments were collected for each patient. Predictors of in-hospital mortality were investigated. RESULTS: Overall, 531 (3.9%) patients were admitted for bleeding: 189 clinically relevant non-major bleeding, 106 cerebral and 236 major non-cerebral (95.8% gastrointestinal (GI)). Among 106 cerebral bleedings, 28.3% and 24.5% were typical and atypical intracranial, respectively, and 47.2% were subdural haemorrhages. Most of patients with GI bleeding presented with anaemia (90.7%). A similar rate of GI bleeding was found in aspirin-treated patients taking or not proton pump inhibitors (PPI). In-hospital mortality was 9.98%. Age ≥80 years (odds ratio (OR) 2.513, p=.005), cerebral bleeding (OR 5.373, p<.001), eGFR <30 ml/min/m2 (OR 2.388, p=.035) and COPD (OR 2.362, p=.024) were positively associated with mortality, while ACE inhibitors/ARBs use was negatively associated (OR 0.383, p=.028). CONCLUSIONS: The most frequent type of major haemorrhage was GI bleeding, which was not modified by the use of PPI in patients taking aspirin. Cerebral bleeding increased all-cause death, which was lower in ACE inhibitors/ARBs users. KEY MESSAGE Gastrointestinal (GI) bleeding was the most common reason for hospital admission. The rate of GI bleeding was similar in patients on aspirin using or not PPI. Cerebral bleeding increased in-hospital mortality, which was lower in patients taking ACE inhibitors/ARBs.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32829405

RESUMO

BACKGROUND: Despite the widespread use of erythropoiesis-stimulating agents (ESAs) to treat anaemia, the risk of adverse outcomes associated with the use of different types of ESAs in non-dialysis chronic kidney disease (CKD) is poorly investigated. METHODS: From a pooled cohort of four observational studies, we selected CKD patients receiving short-acting (epoetin α/ß; n = 299) or long-acting ESAs (darbepoetin and methoxy polyethylene glycol-epoetin ß; n = 403). The primary composite endpoint was end-stage kidney disease (ESKD; dialysis or transplantation) or all-cause death. Multivariable Cox models were used to estimate the relative risk of the primary endpoint between short- and long-acting ESA users. RESULTS: During follow-up [median 3.6 years (interquartile range 2.1-6.3)], the primary endpoint was registered in 401 patients [166 (72%) in the short-acting ESA group and 235 (58%) in the long-acting ESA group]. In the highest tertile of short-acting ESA dose, the adjusted risk of primary endpoint was 2-fold higher {hazard ratio [HR] 2.07 [95% confidence interval (CI) 1.37-3.12]} than in the lowest tertile, whereas it did not change across tertiles of dose for long-acting ESA patients. Furthermore, the comparison of ESA type in each tertile of ESA dose disclosed a significant difference only in the highest tertile, where the risk of the primary endpoint was significantly higher in patients receiving short-acting ESAs [HR 1.56 (95% CI 1.09-2.24); P = 0.016]. Results were confirmed when ESA dose was analysed as continuous variable with a significant difference in the primary endpoint between short- and long-acting ESAs for doses >105 IU/kg/week. CONCLUSIONS: Among non-dialysis CKD patients, the use of a short-acting ESA may be associated with an increased risk of ESKD or death versus long-acting ESAs when higher ESA doses are prescribed.

10.
Biomolecules ; 10(7)2020 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-32635659

RESUMO

Janus kinase inhibitors (JAKi) belong to a new class of oral targeted disease-modifying drugs which have recently revolutionized the therapeutic panorama of rheumatoid arthritis (RA) and other immune-mediated diseases, placing alongside or even replacing conventional and biological drugs. JAKi are characterized by a novel mechanism of action, consisting of the intracellular interruption of the JAK-STAT pathway crucially involved in the immune response. The aim of this narrative review is to globally report the most relevant pharmacological features and clinical outcomes of the developed and incoming JAKi for RA, based on the available preclinical and clinical evidence. A total of 219 papers, including narrative and systematic reviews, randomized controlled trials (RCTs), observational studies, case reports, guidelines, and drug factsheets, were selected. The efficacy and safety profile of both the first generation JAKi (baricitinib and tofacitinib) and the second generation JAKi (upadacitinib, filgotinib, peficitinib, decernotinib and itacitinib) were compared and discussed. Results from RCTs and real-life data are encouraging and outline a rapid onset of the pharmacologic effects, which are maintained during the time. Their efficacy and safety profile are comparable or superior to those of biologic agents and JAKi proved to be efficacious when given as monotherapy. Finally, the manufacturing of JAKi is relatively easier and cheaper than that of biologics, thus increasing the number of compounds being formulated and tested for clinical use.

11.
Int J Antimicrob Agents ; 56(2): 106053, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32534189

RESUMO

The emergence of the new COVID-19 virus is proving to be a challenge in seeking effective therapies. Since the most severe clinical manifestation of COVID-19 appears to be a severe acute respiratory syndrome, azithromycin has been proposed as a potential treatment. Azithromycin is known to have immunomodulating and antiviral properties. In vitro studies have demonstrated the capacity of azithromycin in reducing production of pro-inflammatory cytokines such as IL-8, IL-6, TNF alpha, reduce oxidative stress, and modulate T-helper functions. At the same time there are multiple clinical evidences of the role of azithromycin in acute respiratory distress syndrome and against Middle East Respiratory syndrome (MERS). Some preliminary evidence has demonstrated controversial results regarding efficacy of azithromycin in combination with hydroxychloroquine in COVID-19. First, a French trial demonstrated 100% virological negativizing of six patients treated with azithromycin plus hydroxychloroquine vs. 57.1% of patients treated with only hydroxychloroquine and 12.5% of the control group (P < 0.05). On the other hand, another case series revealed no efficacy at all on 11 patients treated with the same combination and doses. Furthermore, there are some concerns regarding the association of azithromycin and hydroxychloroquine because of potential QT prolongation. In fact, both drugs have this as a potential side effect and evidence regarding the safe use of this combination is controversial. Despite the necessity to quickly find solutions for COVID-19, extreme caution must be used in evaluating the risk-benefit balance. However, based on preclinical and clinical evidence and some preliminary results in COVID-19, azithromycin could have potential in the fight against this new disease.


Assuntos
Azitromicina/uso terapêutico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/patologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Síndrome do QT Longo/induzido quimicamente , Pandemias , Pneumonia Viral/virologia
13.
Pharmacol Res ; 157: 104849, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32360482

RESUMO

Taking anti-inflammatory drugs, including non-steroidal (NSAIDs), during Covid-19 infection, how much is risky? The French Minister of Health, who has raised an alarm on a possible risk deriving from the use of ibuprofen for the control of fever and other symptoms during the disease, opened the debate a few days ago. In this paper we examine available evidence from preclinical and clinical studies that had analysed the role of COX in the inflammatory process and the effects of NSAIDs in patients with infections. Most of the published studies that suggested not protective effects of NSAIDs were mainly performed in vitro or on animals. Therefore, their meaning in humans is to be considered with great caution. Based also on data suggesting protective effects of NSAIDs, we concluded that currently there is no evidence suggesting a correlation between NSAIDs and a worsening of infections. Further studies will be certainly needed to better define the role of NSAIDs and particularly COX2 inhibitors in patients with infections. In the meantime, we must wait for results of the revision started by the PRAC on May 2019 on the association ibuprofen/ketoprofen​​​​​​ and worsening of infections. Since nowadays no scientific evidence establishes a correlation between NSAIDS and worsening of COVID-19, patients should be advice against any NSAIDs self-medication when COVID-19 like symptoms are present.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Viroses/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Humanos , Pandemias
15.
Cancer Treat Rev ; 79: 101893, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31499407

RESUMO

BACKGROUND: The management of locally advanced rectal cancer (RC) is an evolving clinical field where the multidisciplinary approach can reach its best, and liquid biopsy for obtaining tumor-derived component such as circulating tumor DNA (ctDNA) might provide complementary informations. METHODS: A systematic review of studies available in literature of liquid biopsy in non-metastatic RC has been performed according to PRISMA criteria to assess the role of ctDNA as a diagnostic, predictive and prognostic biomarker in this setting. RESULTS: Twenty-five publications have been retrieved, of which 8 full-text articles, 7 abstracts and 10 clinical trials. Results have been categorized into three groups: diagnostic, predictive and prognostic. Few but promising data are available about the use of liquid biopsy for early diagnosis of RC, with the main limitation of sensitivity due to low concentrations of ctDNA in this setting. In terms of prediction of response to chemoradiation, still inconclusive data are available about the utility of a pre-treatment liquid biopsy, whereas some studies report a positive correlation with a dynamic (pre/post-treatment) monitoring. The presence of minimal residual disease by ctDNA was consistently associated with worse prognosis across studies. CONCLUSIONS: The use of liquid biopsy for monitoring response to chemoradiation and assess the risk of disease recurrence are the most advanced potential applications for liquid biopsy in RC, with implications also in the context of non-operative management strategies.


Assuntos
Biomarcadores Tumorais , Biópsia Líquida , Neoplasias Retais/diagnóstico , DNA Tumoral Circulante , DNA de Neoplasias , Humanos , Biópsia Líquida/métodos , Metástase Neoplásica , Estadiamento de Neoplasias , Células Neoplásicas Circulantes , Prognóstico , Neoplasias Retais/etiologia , Neoplasias Retais/mortalidade , Neoplasias Retais/terapia , Recidiva , Resultado do Tratamento
16.
Riv Psichiatr ; 54(4): 137-149, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379379

RESUMO

AIM: To provide a review of the clinically relevant evidence pertaining to the use of trazodone in major depressive disorder. METHODS: Medline and Cochrane Library searches were searched using the keywords 'trazodone' AND 'depression', to identify the most relevant literature pertinent to the pharmacological properties of trazodone and its use in clinical practice. Articles that were selected included basic pharmacology papers, clinical trials, clinical practice guidelines, and reviews. Related references were cross checked. European and United States prescribing information was reviewed as well. An effort was made to give weight to the information that was most relevant for daily clinical practice. RESULTS: Trazodone is an antidepressant with a mechanism of action that remains innovative and with a favorable profile for the treatment of depression. The appropriate antidepressant doses are usually 150-300 mg/day and are often higher than the doses that are used when trazodone is prescribed to augment the antidepressant effect of another medication, for instance when trazodone is prescribed to address insomnia in a patient treated with an SSRI. Trazodone is usually well tolerated and has a low risk of anticholinergic side effects, weight gain and sexual side effects. DISCUSSION: Trazodone is an established medication that is efficacious for the treatment of a broad array of depressive symptoms, including symptoms that are less likely to respond to other antidepressants (e.g. SSRI), such as insomnia. As an antidepressant, trazodone has proven as efficacious as the tricyclic and second-generation antidepressants and is tolerated relatively well. Trazodone may be helpful for patients with major depression and comorbid insomnia, anxiety or psychomotor agitation. CONCLUSIONS: Trazodone is efficacious antidepressants with a relatively low risks of side effects such as weight gain, sexual or anticholinergic effects (such as constipation, urinary retention, dry mouth). In addition to being able to control a wide range of depressive symptoms, trazodone may improve sleep and be particularly helpful for patients whose symptoms of depression include insomnia.


Assuntos
Antidepressivos de Segunda Geração , Transtorno Depressivo Maior/tratamento farmacológico , Trazodona , Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/metabolismo , Antidepressivos de Segunda Geração/farmacologia , Antidepressivos de Segunda Geração/uso terapêutico , Ansiedade/tratamento farmacológico , Bulimia/tratamento farmacológico , Preparações de Ação Retardada , Interações Medicamentosas , Fibromialgia/tratamento farmacológico , Humanos , Transtornos Neurocognitivos/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Trazodona/efeitos adversos , Trazodona/metabolismo , Trazodona/farmacologia , Trazodona/uso terapêutico
17.
Int J Antimicrob Agents ; 54(5): 562-571, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31279152

RESUMO

Ceftaroline fosamil is a fifth-generation cephalosporin with anti-methicillin-resistant Staphylococcus aureus (MRSA) activity. It has been approved by the EMA and FDA for the treatment of adults and children with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). However, ceftaroline fosamil has a broad spectrum of activity, and a good safety and tolerability profile, so is frequently used off-label. The aim of this systematic review was to summarize the safety and efficacy of off-label use of ceftaroline. The review was conducted according to PRISMA guidelines. MEDLINE, EMBASE and CENTRAL databases (2010-2018) were searched using as the main term ceftaroline fosamil and its synonyms in combination with names of infectious diseases of interest. A total of 21 studies with 1901 patients were included: the most common off-label indications for ceftaroline use were bacteremia (n=595), endocarditis (n=171), osteoarticular infections (n=368), hospital-acquired pneumonia (n=115) and meningitis (n=23). The most common reasons for off-label use were persistent or recurrent infection after standard treatment or non-susceptibility to vancomycin and daptomycin. Clinical success was evaluated in 933 patients, and 724 (77%) of these reached this positive outcome. Incidence of adverse events (AEs) was reported in 11 studies. In 83 (9%) cases there were AEs related to the use of ceftaroline; the most common reported AEs were nausea, vomiting, diarrhea, rash and neutropenia. The review results show that ceftaroline may be used in clinical settings other than those currently approved; however, the use of ceftaroline in these contexts deserves further investigation.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Uso Off-Label/estatística & dados numéricos , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Infecções Comunitárias Adquiridas/microbiologia , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Pneumonia Associada a Assistência à Saúde/microbiologia , Humanos , Meningite/tratamento farmacológico , Meningite/microbiologia
18.
Eur J Clin Microbiol Infect Dis ; 38(6): 1153-1162, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30840159

RESUMO

To illustrate the effectiveness of our intensive multidisciplinary management (IMM) in the treatment of severely ill patients with necrotizing soft tissue infections (NSTIs). A retrospective observational study was conducted in a general ICU. Thirty-two consecutive patients undergoing IMM were carefully compared with 30 consecutive patients receiving a standard management (SM). IMM combined intensive care management, early surgical debridement followed by daily inspection of surgical wounds, close microbiological surveillance, and targeted high-dose antibiotics. IMM was associated with the better decrease of daily SOFA score (p = 0.04). Also, IMM caused + 12% increase in the overall number of surgical procedures (p = 0.022) and a higher number of tissue biopsies/per day (median 0.63 versus 0.32; p = 0.025), leading to a more targeted antimicrobial changes (89.6% vs 51.6%; p < 0.00001). High-dose daptomycin (75% vs 36.7%; p = 0.002) and extended/continuous infusion of beta-lactams (75% vs 43.3%; p = 0.011) were more frequently utilized. A specific efficiency score correlated with the decrease of SOFA score (efficacy) in IMM patients only (p = 0.027). Finally, IMM was associated with a significant lower ICU mortality rate (15.6% vs 40%; p = 0.032). IMM was more effective than SM as it allowed the earlier control of infection and the faster reduction of multiple organ-dysfunction.


Assuntos
Cuidados Críticos/métodos , Necrose/terapia , Infecções dos Tecidos Moles/terapia , Adulto , Idoso , Anti-Infecciosos/uso terapêutico , Cuidados Críticos/normas , Desbridamento , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Necrose/patologia , Escores de Disfunção Orgânica , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Infecções dos Tecidos Moles/mortalidade , Infecções dos Tecidos Moles/patologia
19.
Drug Metab Pers Ther ; 34(1)2019 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-30840585

RESUMO

Background The thiopurine S-methyltransferase (TPMT)/azathioprine (AZA) gene-drug pair is one of the most well-known pharmacogenetic markers. Despite this, few studies investigated the implementation of TPMT testing and the combined evaluation of genotype and phenotype in multidisciplinary clinical settings where patients are undergoing chronic therapy with AZA. Methods A total of 356 AZA-treated patients for chronic autoimmune diseases were enrolled. DNA was isolated from whole blood and the samples were analyzed for the c.460G>A and c.719A>G variants by the restriction fragment length polymorphism (RFLP) technique and sequenced for the c.238G>C variant. The TPMT enzyme activity was determined in erythrocytes by a high-performance liquid chromatography (HPLC) assay. Results All the patients enrolled were genotyped while the TPMT enzyme activity was assessed in 41 patients. Clinical information was available on 181 patients. We found no significant difference in the odds of having adverse drug reactions (ADRs) in wild-type patients and variant allele carriers, but the latter had an extra risk of experiencing hematologically adverse events. The enzyme activity was significantly associated to genotype. Conclusions TPMT variant allele carriers have an extra risk of experiencing hematologically adverse events compared to wild-type patients. Interestingly, only two out of 30 (6.6%) patients had discordant results between genotype, phenotype and onset of ADRs.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Azatioprina/efeitos adversos , Azatioprina/uso terapêutico , Genótipo , Metiltransferases/genética , Fenótipo , Doenças Autoimunes/enzimologia , Doenças Autoimunes/genética , Cromatografia Líquida de Alta Pressão , Doença Crônica , Eritrócitos/efeitos dos fármacos , Feminino , Humanos , Itália , Masculino , Metiltransferases/metabolismo
20.
Immunotherapy ; 11(3): 241-254, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30730275

RESUMO

The aim of this review is to report the current evidence on immunogenicity of monoclonal antibodies (moAbs) used in cancer compared with autoimmune diseases, focusing on local microenvironment. English abstracts were identified in Medline and www.clinicaltrials.gov . A total of 82 papers were selected. The percentage of immunogenicity of moAbs used for cancer therapy, evaluated as the serum concentration of antidrug antibodies, is significantly lower than that of moAbs used for the treatment of autoimmune diseases. This condition may rely on a different immunologic background characterized by a hyperactivation of immune cells in autoimmune diseases. The formation of complexes between antidrug antibodies and non-neutralizing moAbs bound to neoplastic antigens may allow more efficient elimination of cancer cells, but additional studies are needed.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Neoplasias/tratamento farmacológico , Anticorpos Anti-Idiotípicos/sangue , Anticorpos Anti-Idiotípicos/imunologia , Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Doenças Autoimunes/imunologia , Humanos , Neoplasias/imunologia , Microambiente Tumoral
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