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1.
Nephrol Dial Transplant ; 38(7): 1591-1602, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35998321

RESUMO

Posttransplant malignancies, particularly recurrent and de novo, in solid organs including kidney transplant recipients (KTRs) are a significant complication associated with substantial mortality, largely attributed to the long-term immunosuppression necessary to maintain allograft tolerance. Older age at transplantation and oncogenic virus infection along with pretransplant malignancies are among the main factors contributing to the risk of cancer in this population. As the mean age of transplant candidates rises, the rate of transplant recipients with pretransplant malignancies also increases. The eligibility criteria for transplantation in patients with prior cancer have recently changed. The overall risk of posttransplant malignancies is at least double after transplantation, including KTRs, relative to the general population, and is most pronounced for skin cancers associated with UV radiation and virally mediated tumors. The risk of renal cell carcinoma is specifically increased in the kidney transplant population. The therapy for cancer in transplant patients is associated with risk of higher toxicity, and graft rejection and/or impairment, which poses a unique challenge in its management. Reduction of immunosuppression and the use of mammalian target of rapamycin inhibitors are common after cancer diagnosis, although optimal immunosuppression for transplant recipients with cancer remains undefined. Suboptimal cancer treatment contributing to a worse prognosis has been reported for malignancies in this population. In this article, we focus on the prevalence and outcomes of posttransplant malignancies, cancer therapy including a short overview of immunotherapy, cancer screening and prevention strategies, and immunosuppression as a cancer risk factor. The 2020/2021 recommendations of the Kidney Disease: Improving Global Outcomes and the American Society of Transplantation for transplant candidates with a history of cancer are presented.


Assuntos
Nefropatias , Transplante de Rim , Neoplasias , Humanos , Adulto , Transplante de Rim/efeitos adversos , Neoplasias/complicações , Neoplasias/epidemiologia , Fatores de Risco , Terapia de Imunossupressão/efeitos adversos , Nefropatias/etiologia , Transplantados
2.
Neuroimage ; 264: 119747, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36403733

RESUMO

Magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs) has been hailed as the future of electrophysiological recordings from the human brain. In this work, we investigate how the dimensions of the sensing volume (the vapour cell) affect the performance of both a single OPM-MEG sensor and a multi-sensor OPM-MEG system. We consider a realistic noise model that accounts for background brain activity and residual noise. By using source reconstruction metrics such as localization accuracy and time-course reconstruction accuracy, we demonstrate that the best overall sensitivity and reconstruction accuracy are achieved with cells that are significantly longer and wider that those of the majority of current commercial OPM sensors. Our work provides useful tools to optimise the cell dimensions of OPM sensors in a wide range of environments.


Assuntos
Mapeamento Encefálico , Magnetoencefalografia , Humanos , Magnetoencefalografia/métodos , Mapeamento Encefálico/métodos , Encéfalo/fisiologia
3.
Age Ageing ; 51(6)2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35697352

RESUMO

BACKGROUND: a suspected urinary tract infection (UTI) is the most common reason to prescribe antibiotics in a frail older patient. Frequently, antibiotics are prescribed unnecessarily. To increase appropriate antibiotic use for UTIs through antibiotic stewardship interventions, we need to thoroughly understand the factors that contribute to these prescribing decisions. OBJECTIVES: (1) to obtain insight into factors contributing to antibiotic prescribing for suspected UTIs in frail older adults. (2) To develop an overarching model integrating these factors to guide the development of antibiotic stewardship interventions for UTIs in frail older adults. METHODS: we conducted an exploratory qualitative study with 61 semi-structured interviews in older adult care settings in Poland, the Netherlands, Norway and Sweden. We interviewed physicians, nursing staff, patients and informal caregivers. RESULTS: participants described a chain of decisions by patients, caregivers and/or nursing staff preceding the ultimate decision to prescribe antibiotics by the physician. We identified five themes of influence: (1) the clinical situation and its complexity within the frail older patient, (2) diagnostic factors, such as asymptomatic bacteriuria, (3) knowledge (gaps) and attitude, (4) communication: interprofessional, and with patients and relatives and (5) context and organisation of care, including factors such as availability of antibiotics (over the counter), antibiotic stewardship efforts and factors concerning out-of-hours care. CONCLUSIONS: decision-making on suspected UTIs in frail older adults is a complex, multifactorial process. Due to the diverse international setting and stakeholder variety, we were able to provide a comprehensive overview of factors to guide the development of antibiotic stewardship interventions.


Assuntos
Gestão de Antimicrobianos , Infecções Urinárias , Idoso , Antibacterianos/uso terapêutico , Idoso Fragilizado , Humanos , Prescrição Inadequada/prevenção & controle , Pesquisa Qualitativa , Infecções Urinárias/diagnóstico , Infecções Urinárias/tratamento farmacológico
4.
Molecules ; 27(23)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36500541

RESUMO

A solvent-free two-step synthesis of polyfunctionalized pyrazoles under ball-milling mechanochemical conditions was developed. The protocol comprises (3 + 2)-cycloaddition of in situ generated nitrile imines and chalcones, followed by oxidation of the initially formed 5-acylpyrazolines with activated MnO2. The second step proceeds via an exclusive deacylative pathway, to give a series of 1,4-diarylpyrazoles functionalized with a fluorinated (CF3) or non-fluorinated (Ph, COOEt, Ac) substituent at C(3) of the heterocyclic ring. In contrast, MnO2-mediated oxidation of a model isomeric 4-acylpyrazoline proceeded with low chemoselectivity, leading to fully substituted pyrazole as a major product formed via dehydrogenative aromatization. The presented approach extends the scope of the known methods carried out in organic solvents and enables the preparation of polyfunctionalized pyrazoles, which are of general interest in medicine and material sciences.


Assuntos
Compostos de Manganês , Óxidos , Iminas , Reação de Cicloadição , Oxirredução , Solventes
5.
Neuroimage ; 226: 117497, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33132074

RESUMO

Optically Pumped Magnetometers (OPMs) have been hailed as the future of human magnetoencephalography, as they enable a level of flexibility and adaptability that cannot be obtained with systems based on superconductors. While OPM sensors are already commercially available, there is plenty of room for further improvements and customization. In this work, we detected auditory evoked brain fields using an OPM based on the nonlinear magneto-optical rotation (NMOR) technique. Our sensor head, containing only optical and non-magnetizable elements, is connected to an external module including all the electronic components, placed outside the magnetically shielded room. The use of the NMOR allowed us to detect the brain signals in non-zero magnetic field environments. In particular, we were able to detect auditory evoked fields in a background field of 70 nT. We benchmarked our sensor with conventional SQUID sensors, showing comparable performance. We further demonstrated that our sensor can be employed to detect modulations of brain oscillations in the alpha band. Our results are a promising stepping-stone towards the realization of resilient OPM-based magnetoencephalography systems that do not require active compensation.


Assuntos
Encéfalo/fisiologia , Desenho de Equipamento , Potenciais Evocados Auditivos/fisiologia , Magnetoencefalografia/instrumentação , Adulto , Humanos , Masculino
6.
BMC Fam Pract ; 22(1): 183, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34517844

RESUMO

BACKGROUND: Patient safety is defined as an activity that minimizes and removes possible errors and injuries to patients. A number of factors have been found to influence patient safety management, including the facilities available in the practice, communication and collaboration, education regarding patient safety and generic conditions. This study tested a theoretical model of patient safety interventions based on safety antecedents. METHODS: Medical professionals were surveyed using a questionnaire developed by Gaal et al. The results were analyzed with SPSS 20 and AMOS. A hypothetical model of direct and indirect effects on patient safety in a primary care environment was created and analyzed using structural equation modeling (SEM). RESULTS: SEM proved to be an effective tool to analyse safety in primary care. The facilities in the practice appear to have no significant influence on patient safety management in the case of female respondents, those below mean age, those who are not GPs (general practitioner) and respondents not working in counselling centres. CONCLUSIONS: The integrated safety model described in the study can improve patient safety management.


Assuntos
Clínicos Gerais , Segurança do Paciente , Feminino , Humanos , Análise de Classes Latentes , Atenção Primária à Saúde , Gestão da Segurança
7.
Int J Mol Sci ; 22(22)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34830123

RESUMO

New drugs, including immune checkpoint inhibitors and targeted therapy, have changed the prognosis in a subset of patients with advanced lung cancer, and are now actively investigated in a number of trials with neoadjuvant and adjuvant regimens. However, no phase III randomized studies were published yet. The current narrative review proves that targeted therapies are safe in neoadjuvant approach. Unsurprisingly, administration of therapy is related to an acceptable toxicity profile. Severe adverse events' rate that rarely compromises outcomes of patients with advanced lung cancer is not that commonly accepted in early lung cancer as it may lead to missing the chance of curative surgery. Among those complications, the most important factors that may limit the use of targeted therapies are severe respiratory adverse events precluding the resection occurring after treatment with some anaplastic lymphoma kinase and rarely after epidermal growth factor receptor tyrosine kinase inhibitors. At this point, in the presented literature assessing the feasibility of neoadjuvant therapies with anaplastic lymphoma kinase and epidermal growth factor receptor tyrosine kinase inhibitors, we did not find any unexpected intraoperative events that would be of special interest to a thoracic surgeon. Moreover, the postoperative course was associated with typical rate of complications.


Assuntos
Quinase do Linfoma Anaplásico/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Inibidores de Proteínas Quinases/uso terapêutico , Quinase do Linfoma Anaplásico/metabolismo , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Diarreia/induzido quimicamente , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/cirurgia , Náusea/induzido quimicamente , Terapia Neoadjuvante/métodos , Inibidores de Proteínas Quinases/efeitos adversos
8.
Phys Rev Lett ; 125(2): 020403, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32701314

RESUMO

We experimentally realize a method to produce nonequilibrium Bose-Einstein condensates with condensed fraction exceeding those of equilibrium samples with the same parameters. To do this, we immerse an ultracold Bose gas of ^{87}Rb in a cloud of ^{39}K with substantially higher temperatures, providing a controlled source of dissipation. By combining the action of the dissipative environment with evaporative cooling, we are able to progressively distil the nonequilibrium Bose-Einstein condensate from the thermal cloud. We show that by increasing the strength of the dissipation it is even possible to produce condensates above the critical temperature. We finally demonstrate that our out-of-equilibrium samples are long lived and do not reach equilibrium in a time that is accessible for our experiment. Due to its high degree of control, our distillation process is a promising tool for the engineering of open quantum systems.

9.
Opt Express ; 26(18): 22783-22792, 2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30184933

RESUMO

Multi-core optical fibers are readily used in endoscopic devices to transmit classical images. As an extension to the quantum domain, we study the transmission of the spatial quantum fluctuations of light through a conduit made of the ordered packing of thousands of fibers. Starting from twin beams that are correlated in their local intensity fluctuations, we show that, in the limit of a high density of constituent fiber cores, the intensity-difference squeezing present in arbitrary matching regions of the beams is preserved when one of the beams is sent through the conduit. The capability of using fiber bundles to transport quantum information encoded in the spatial degrees of freedom could bring guided-light technology to the emergent field of quantum imaging.

10.
Health Expect ; 21(1): 387-395, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28960624

RESUMO

BACKGROUND: Pandemics of new and emerging infectious diseases are unpredictable, recurrent events that rapidly threaten global health and security. We aimed to identify public views regarding provision of information and consent to participate in primary and critical care clinical research during a future influenza-like illness pandemic. METHODS: Descriptive-interpretive qualitative study, using focus groups (n = 10) and semi-structured interviews (n = 16), with 80 members of the public (>18 years) in Belgium, Spain, Poland and the UK. Local qualitative researchers followed a scenario-based topic guide to collect data. Data were transcribed verbatim, translated into English and subject to framework analysis. RESULTS: Public understandings of pandemics were shaped by personal factors (illness during the previous H1N1 pandemic, experience of life-threatening illness) and social factors (historical references, media, public health information). Informants appreciated safeguards provided by ethically robust research procedures, but current enrolment procedures were seen as a barrier. They proposed simplified enrolment processes for higher risk research and consent waiver for certain types of low-risk research. Decision making about research participation was influenced by contextual, research and personal factors. Informants generally either carefully weighed up various approaches to research participation or responded instinctively. They supported the principle of using routinely collected, anonymized clinical biological samples for research without explicit consent, but regarded this as less acceptable if researchers were motivated primarily by commercial gain. CONCLUSIONS: This bottom-up approach to ascertaining public views on pandemic clinical research has identified support for more proportionate research protection procedures for publically funded, low-risk studies.


Assuntos
Pesquisa Biomédica , Participação da Comunidade , Surtos de Doenças , Pandemias/prevenção & controle , Participação do Paciente , Adulto , Idoso , Europa (Continente) , Feminino , Grupos Focais , Humanos , Consentimento Livre e Esclarecido , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa
11.
JAMA ; 319(17): 1781-1789, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29710295

RESUMO

Importance: The use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for lower urinary tract infection (UTI). Objective: To compare the clinical and microbiologic efficacy of nitrofurantoin and fosfomycin in women with uncomplicated cystitis. Design, Setting, and Participants: Multinational, open-label, analyst-blinded, randomized clinical trial including 513 nonpregnant women aged 18 years and older with symptoms of lower UTI (dysuria, urgency, frequency, or suprapubic tenderness), a positive urine dipstick result (with detection of nitrites or leukocyte esterase), and no known colonization or previous infection with uropathogens resistant to the study antibiotics. Recruitment took place from October 2013 through April 2017 at hospital units and outpatient clinics in Geneva, Switzerland; Lodz, Poland; and Petah-Tiqva, Israel. Interventions: Participants were randomized in a 1:1 ratio to oral nitrofurantoin, 100 mg 3 times a day for 5 days (n = 255), or a single 3-g dose of oral fosfomycin (n = 258). They returned 14 and 28 days after therapy completion for clinical evaluation and urine culture collection. Main Outcomes and Measures: The primary outcome was clinical response in the 28 days following therapy completion, defined as clinical resolution (complete resolution of symptoms and signs of UTI without prior failure), failure (need for additional or change in antibiotic treatment due to UTI or discontinuation due to lack of efficacy), or indeterminate (persistence of symptoms without objective evidence of infection). Secondary outcomes included bacteriologic response and incidence of adverse events. Results: Among 513 patients who were randomized (median age, 44 years [interquartile range, 31-64]), 475 (93%) completed the trial and 377 (73%) had a confirmed positive baseline culture. Clinical resolution through day 28 was achieved in 171 of 244 patients (70%) receiving nitrofurantoin vs 139 of 241 patients (58%) receiving fosfomycin (difference, 12% [95% CI, 4%-21%]; P = .004). Microbiologic resolution occurred in 129 of 175 (74%) vs 103 of 163 (63%), respectively (difference, 11% [95% CI, 1%-20%]; P = .04). Adverse events were few and primarily gastrointestinal; the most common were nausea and diarrhea (7/248 [3%] and 3/248 [1%] in the nitrofurantoin group vs 5/247 [2%] and 5/247 [1%] in the fosfomycin group, respectively). Conclusions and Relevance: Among women with uncomplicated UTI, 5-day nitrofurantoin, compared with single-dose fosfomycin, resulted in a significantly greater likelihood of clinical and microbiologic resolution at 28 days after therapy completion. Trial Registration: ClinicalTrials.gov Identifier: NCT01966653.


Assuntos
Anti-Infecciosos Urinários/uso terapêutico , Fosfomicina/administração & dosagem , Nitrofurantoína/administração & dosagem , Infecções Urinárias/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos Urinários/efeitos adversos , Esquema de Medicação , Farmacorresistência Bacteriana , Feminino , Fosfomicina/efeitos adversos , Humanos , Pessoa de Meia-Idade , Nitrofurantoína/efeitos adversos , Resultado do Tratamento , Urina/microbiologia , Adulto Jovem
12.
Postepy Dermatol Alergol ; 35(2): 128-138, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29760611

RESUMO

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is one of the aggressive rare hematopoietic malignancies with predilection to the skin, primarily found in adults. The precise incidence of BPDCN is difficult to estimate due to constantly changing nomenclature and lack of precise defining criteria prior to the 2008 WHO classification system. There are not many cases described in the literature, what makes the diagnostic process challenging. Skin lesions such as erythematous infiltrates and nodules are usually the first manifestation of the disease. Therefore, in doubtful diagnostic cases, dermatologists should perform histopathological and immunohistochemistry examinations along with hematological and oncological cooperation, as early diagnosis and appropriate treatment is essential for improvement of the disease course. This analysis, despite the small number of patients may provide useful information on the clinical and histopathological features of this rare malignancy.

13.
Opt Express ; 25(17): 19701-19710, 2017 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-29041658

RESUMO

We use a coherent fiber bundle to demonstrate the endoscopic absorption imaging of quantum gases. We show that the fiber bundle introduces spurious noise in the picture mainly due to the strong core-to-core coupling. By direct comparison with free-space pictures, we observe that there is a maximum column density that can be reliably measured using our fiber bundle, and we derive a simple criterion to estimate it. We demonstrate that taking care of not exceeding such maximum, we can retrieve exact quantitative information about the atomic system, making this technique appealing for systems requiring isolation form the environment.

14.
Wiad Lek ; 70(4): 778-783, 2017.
Artigo em Polonês | MEDLINE | ID: mdl-29064805

RESUMO

Thyroid diseases belong to the most common disorders of the ductless glands. Particular attention is paid to the growing morbidity of autoimmune affliction of the thyroid gland, including Hashimoto's thyroiditis. The main method of treatment is an oral substitution of thyroid hormones. However, the literature pays particular attention to supporting therapy with a diet rich in components essential for the proper functioning of this organ.


Assuntos
Doença de Hashimoto/tratamento farmacológico , Oligoelementos/administração & dosagem , Adulto , Feminino , Doença de Hashimoto/prevenção & controle , Humanos , Tireotropina/administração & dosagem
15.
Breast Cancer Res ; 18(1): 43, 2016 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-27117582

RESUMO

BACKGROUND: A better understanding of immune response in breast cancer brain metastases (BCBM) may prompt new preventive and therapeutic strategies. METHODS: Immunohistochemical expression of stromal tumor-infiltrating lymphocytes (TILs: CD4, CD8, CTLA4), macrophage/microglial cells (CD68), programmed cell death protein 1 receptor (PD-1), programmed cell death protein 1 receptor ligand (PD-L)1, PD-L2 and glial fibrillary acid protein was assessed in 84 BCBM and their microenvironment. RESULTS: Median survival after BCBM excision was 18.3 months (range 0-99). Median number of CD4+, CD8+ TILs and CD68+ was 49, 69 and 76 per 1 mm(2), respectively. PD-L1 and PD-L2 expression in BCBM was present in 53 % and 36 % of cases, and was not related to BCBM phenotype. PD-1 expression on TILs correlated positively with CD4+ and CD8+ TILs (r = 0.26 and 0.33), and so did CD68+ (r = 0.23 and 0.27, respectively). In the multivariate analysis, survival after BCBM excision positively correlated with PD-1 expression on TILs (hazard ratio (HR) = 0.3, P = 0.003), CD68+ infiltration (HR = 0.2, P < 0.001), brain radiotherapy (HR = 0.1, P < 0.001), endocrine therapy (HR = 0.1, P < 0.001), and negatively with hormone-receptor-negative/human epidermal growth factor receptor 2 (HER2)-positive phenotype of primary tumor (HR = 2.6, P = 0.01), HER2 expression in BCBM (HR = 4.9, P = 0.01). CONCLUSIONS: PD-L1 and PD-L2 expression is a common occurrence in BCBM, irrespective of primary tumor and BCBM phenotype. Favorable prognostic impact of PD-1 expression on TILs suggests a beneficial effect of preexisting immunity and implies a potential therapeutic role of immune checkpoint inhibitors in BCBM.


Assuntos
Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/secundário , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Microambiente Tumoral/imunologia , Astrócitos/imunologia , Astrócitos/metabolismo , Astrócitos/patologia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Terapia Combinada , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Microglia/imunologia , Microglia/metabolismo , Microglia/patologia , Gradação de Tumores , Fenótipo , Prognóstico , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Modelos de Riscos Proporcionais , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
16.
J Antimicrob Chemother ; 71(11): 3258-3267, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27353466

RESUMO

OBJECTIVES: To determine the effect of amoxicillin treatment on resistance selection in patients with community-acquired lower respiratory tract infections in a randomized, placebo-controlled trial. METHODS: Patients were prescribed amoxicillin 1 g, three times daily (n = 52) or placebo (n = 50) for 7 days. Oropharyngeal swabs obtained before, within 48 h post-treatment and at 28-35 days were assessed for proportions of amoxicillin-resistant (ARS; amoxicillin MIC ≥2 mg/L) and -non-susceptible (ANS; MIC ≥0.5 mg/L) streptococci. Alterations in amoxicillin MICs and in penicillin-binding-proteins were also investigated. ITT and PP analyses were conducted. RESULTS: ARS and ANS proportions increased 11- and 2.5-fold, respectively, within 48 h post-amoxicillin treatment compared with placebo [ARS mean increase (MI) 9.46, 95% CI 5.57-13.35; ANS MI 39.87, 95% CI 30.96-48.78; P < 0.0001 for both]. However, these differences were no longer significant at days 28-35 (ARS MI -3.06, 95% CI -7.34 to 1.21; ANS MI 4.91, 95% CI -4.79 to 14.62; P > 0.1588). ARS/ANS were grouped by pbp mutations. Group 1 strains exhibited significantly lower amoxicillin resistance (mean MIC 2.8 mg/L, 95% CI 2.6-3.1) than group 2 (mean MIC 9.3 mg/L, 95% CI 8.1-10.5; P < 0.0001). Group 2 strains predominated immediately post-treatment (61.07%) and although decreased by days 28-35 (30.71%), proportions remained higher than baseline (18.70%; P = 0.0004). CONCLUSIONS: By utilizing oropharyngeal streptococci as model organisms this study provides the first prospective, experimental evidence that resistance selection in patients receiving amoxicillin is modest and short-lived, probably due to 'fitness costs' engendered by high-level resistance-conferring mutations. This evidence further supports European guidelines that recommend amoxicillin when an antibiotic is indicated for community-acquired lower respiratory tract infections.


Assuntos
Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Infecções Comunitárias Adquiridas/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Seleção Genética , Resistência beta-Lactâmica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amoxicilina/farmacologia , Antibacterianos/farmacologia , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Placebos/administração & dosagem , Pneumonia Bacteriana/microbiologia , Estudos Prospectivos , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Streptococcus/efeitos dos fármacos , Streptococcus/isolamento & purificação , Adulto Jovem
17.
Clin Exp Rheumatol ; 34(1): 88-93, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26842950

RESUMO

OBJECTIVES: The effectiveness of anakinra (interleukin-1 receptor antagonist) in early rheumatoid arthritis (RA) is unknown. We evaluated the efficacy of anakinra (combined with methotrexate) in a randomised clinical trial of early active RA patients. METHODS: The Combination Anti-Rheumatic Drugs in Early RA-2 (CARDERA-2) trial was a randomised trial of early (duration <1 year) active RA. Patients were randomised to 12 months of: (1) methotrexate or (2) anakinra-methotrexate. Follow-up lasted 2 years. The primary outcome was erosive progression (changes from baseline in modified Larsen scores). Secondary outcomes were changes from baseline in disease activity score on a 28-joint count (DAS28), health assessment questionnaire (HAQ), and quality of life (EQ-5D) scores alongside ACR responder rates. RESULTS: 154 patients received the allocated intervention (from 259 screened). Similar Larsen score progression was seen at 12 and 24 months in patients receiving anakinra-methotrexate (mean changes from baseline of 2.50 and 5.10, respectively) and methotrexate monotherapy (mean changes from baseline of 4.16 and 5.20, respectively). Lower improvements in DAS28 and HAQ scores were seen at all time-points in anakinra-methotrexate treated patients; these were significantly less at 24 months (DAS28 p=0.04; HAQ P=0.02). Significantly lower EQ-5D score increases were seen at 12 months with anakinra-methotrexate (p=0.03). Anakinra-methotrexate was associated with more serious adverse events compared with methotrexate monotherapy (11 vs. 6 patients), although this was not significant (p=0.59). CONCLUSIONS: Anakinra (combined with methotrexate) is not effective in early, active RA. It provided no clinical benefits beyond methotrexate monotherapy.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Adulto , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Avaliação da Deficiência , Progressão da Doença , Quimioterapia Combinada , Inglaterra , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Qualidade de Vida , Indução de Remissão , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
18.
Am J Ther ; 23(3): e749-56, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-24732904

RESUMO

Bexarotene, a synthetic retinoid licensed for the treatment of refractory cutaneous T-cell lymphoma (CTCL), has been used clinically in Poland since 2007 in 21 patients. The objective of our retrospective, multicenter study was to evaluate our experience with bexarotene therapy, including efficacy, safety, and survival outcomes. We retrospectively identified 21 adult patients who were treated with bexarotene between the years 2007 and 2012. Starting dose of bexarotene was 300 mg/m per day. The analysis included 3 patients with early-stage mycosis fungoides (MF), 16 patients with advanced-stage MF, and 2 patients with Sézary syndrome (SS). The mean duration of therapy with bexarotene was 14.5 months. Use of bexarotene resulted in an overall response rate of 81.0%, although the overall mortality rate was 52.8%. In our study, early-stage CTCL responded better than advanced-stage CTCL (100.0% vs. 77.8%, respectively). The mean time to observable response was 1.8 months, and the mean duration of the response was 16.4 months. Most significant side effects were hyperlipidemia, hypothyroidism, and a bleeding gastric ulcer. Based on the results of our analysis, bexarotene is a valuable tool in the treatment of refractory early-stage CTCL. Although a majority of patients initially responded to therapy, the high mortality rate in the advanced-stage group suggests that bexarotene does not completely resolve the therapeutic problems in all stages of CTCL. Patient stratification for bexarotene treatment may need a thorough reassessment, in that bexarotene may not be an effective drug in the very advanced stages of CTCL.


Assuntos
Anticarcinógenos/uso terapêutico , Micose Fungoide/tratamento farmacológico , Retinoides/uso terapêutico , Síndrome de Sézary/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Tetra-Hidronaftalenos/uso terapêutico , Administração Cutânea , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticarcinógenos/administração & dosagem , Anticarcinógenos/efeitos adversos , Bexaroteno , Feminino , Humanos , Hiperlipidemias/induzido quimicamente , Hipotireoidismo/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Micose Fungoide/mortalidade , Úlcera Péptica Hemorrágica/induzido quimicamente , Polônia/epidemiologia , Retinoides/administração & dosagem , Retinoides/efeitos adversos , Estudos Retrospectivos , Síndrome de Sézary/mortalidade , Neoplasias Cutâneas/mortalidade , Úlcera Gástrica/induzido quimicamente , Tetra-Hidronaftalenos/administração & dosagem , Tetra-Hidronaftalenos/efeitos adversos , Resultado do Tratamento , Adulto Jovem
19.
Med Pr ; 67(4): 427-33, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27623824

RESUMO

BACKGROUND: Wind instruments musicians are particularly prone to excessive respiratory efforts. Prolonged wind instruments performing may lead to changes in respiratory tracts and thus to respiratory muscles overload. It may result in decreasing lung tissue pliability and, as a consequence, in emphysema. Aim of the research has been to describe basic spirometric parameters for wind players and causes of potential changes. MATERIAL AND METHODS: Slow and forced spirometry with the use of Micro Lab Viasys (Micro Medical, Great Britain) was conducted on 31 wind musicians (group A). A survey concerning playing time and frequency, weight of instruments, and education on diaphragmatic breathing was conducted. The control group included 34 healthy persons at similar age (group B). The results were statistically described using Excel and Statistica programmes. RESULTS: The respiratory parameters were within the range of physiological norms and forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) exceeded in both groups the values of 100%. Forced vital capacity and expiratory vital capacity (EVC) values were significantly lower in the group of musicians than in the control group (p < 0.001). In 45% the group A used diaphragmatic breathing, in 31% of examinees mixed respiratory tract was observed. The significant discrepancy of individual parameters was obtained regarding age and the length of time when performing wind instrument. CONCLUSIONS: Spirometric parameters relative to standards may prove a good respiratory capacity. Peak expiratory flow (PEF) and FEV1 may indicate that a proper technique of respiration during performance was acquired. The length of time when performing wind instrument may influence parameters of dynamic spirometry. Med Pr 2016;67(4):427-433.


Assuntos
Música , Doenças Profissionais/prevenção & controle , Testes de Função Respiratória , Fenômenos Fisiológicos Respiratórios , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Valores de Referência , Respiração , Espirometria , Adulto Jovem
20.
J Antimicrob Chemother ; 70(7): 1989-92, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25766736

RESUMO

OBJECTIVES: The objective was to study changes in the faecal microbiota of patients with uncomplicated urinary tract infections (UTIs) treated with nitrofurantoin and of non-treated healthy controls using 16S rRNA analysis. METHODS: Serial stool samples were collected from patients receiving nitrofurantoin treatment at different timepoints [before treatment (day 1; T1), within 48 h of end of treatment (days 5-15; T2) and 28 days after treatment (days 31-43; T3)], as well as from healthy controls. Direct DNA extraction (PowerSoil DNA Isolation Kit, MoBio Laboratories, Carlsbad, CA, USA) from stool samples was followed by pyrosequencing (454 GS FLX Titanium) of the V3-V5 region of the bacterial 16S rRNA gene. RESULTS: Among UTI patients, mean proportions of the Actinobacteria phylum increased by 19.6% in the first follow-up sample (T2) in comparison with the pretreatment baseline stool sample (T1) (P = 0.026). However, proportions of Actinobacteria reversed to 'normal' pre-antibiotic levels, with a mean difference of 1.0% compared with baseline proportions, in the second follow-up sample (T3). The increase in Actinobacteria was specifically due to an increase in the Bifidobacteriaceae family (Bifidobacterium genus), which constituted 81.0% (95% CI ±7.4%) of this phylum. CONCLUSIONS: No significant impact was observed other than a temporary increase in the beneficial Bifidobacterium genus following nitrofurantoin treatment, which supports its reintroduction into clinical use.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias/classificação , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Metagenômica , Microbiota/efeitos dos fármacos , Nitrofurantoína/farmacologia , Anti-Infecciosos/administração & dosagem , Bactérias/isolamento & purificação , Análise por Conglomerados , DNA Ribossômico/química , DNA Ribossômico/genética , Humanos , Estudos Longitudinais , Dados de Sequência Molecular , Nitrofurantoína/administração & dosagem , Filogenia , Estudos Prospectivos , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Infecções Urinárias/tratamento farmacológico
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