RESUMO
BACKGROUND: Drug survival rates reflect efficacy and safety and may be influenced by the availability of alternative treatment options. Little is known about time-dependent drug survival in psoriasis and the effect of increasing numbers of biologic treatment options. OBJECTIVES: To determine whether drug survival is influenced by the availability of treatment options and by factors such as gender, psoriatic arthritis or previous biologic treatment. METHODS: This observational, retrospective, multicentre cohort study analysed data from patients registered in the Austrian Psoriasis Registry (PsoRA) who were treated with biologics between 1 January 2015 and 30 November 2019. RESULTS: A total of 1572 patients who received 1848 treatment cycles were included in this analysis. The highest long-term Psoriasis Area and Severity Index improvement was observed after treatment with ixekizumab, followed by ustekinumab and secukinumab, adalimumab and etanercept. Overall, ustekinumab surpassed all other biologics in drug survival up to 48 months. However, when adjusted for biologic naïvety, its superiority vanished and drug survival rates were similar for ixekizumab (91·6%), secukinumab (90·2%) and ustekinumab (92·8%), all of them superior to adalimumab (76·5%) and etanercept (71·9%) at 12 months and beyond. Besides biologic non-naïvety (2·10, P < 0·001), the introduction of a new drug such as secukinumab or ixekizumab (relative hazard ratio 1·6, P = 0·001) and female gender (1·50, P = 0·019) increased the risk of treatment discontinuation overall, whereas psoriatic arthritis did not (1·12, P = 0·21). CONCLUSIONS: The time-dependent availability of drugs should be considered when analysing and comparing drug survival. Previous biologic exposure significantly influences drug survival. Women are more likely to stop treatment.
Assuntos
Produtos Biológicos , Psoríase , Adalimumab , Áustria , Estudos de Coortes , Etanercepte , Feminino , Humanos , Psoríase/tratamento farmacológico , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , UstekinumabRESUMO
The epithelioid sarcoma classic, "distal" type was first published in 1970. It is a very rare, malignant, aggressive subcutaneous soft tissue sarcoma that shows characteristic positivity for both epithelial and mesenchymal immunohistochemical markers. It grows very slowly and mostly presents in young men. Clinically the tumor is characterized as a coarse cutaneous or subcutaneous nodular induration that often ulcerates in the course of the disease. An association with trauma is often described and can lengthen time to diagnosis. Most frequently it is found on the flexural side of fingers, the back of the hands, soles of the feet, and extensor sides of arms and legs. Specific for this type of sarcoma is the progression along nerves, tendons, and fasciae. Treatment of choice should be wide excision of the tumor, sentinel node biopsy, and possibly even localized postoperative radiation therapy. Unfortunately the epithelioid sarcoma is very likely to recur and is then associated with metastases in the lung and lymph nodes.
Assuntos
Sarcoma , Úlcera Cutânea , Neoplasias de Tecidos Moles , Humanos , Masculino , Recidiva Local de Neoplasia , Sarcoma/diagnóstico , Sarcoma/patologia , Biópsia de Linfonodo Sentinela , Úlcera Cutânea/diagnóstico , Úlcera Cutânea/patologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/patologiaRESUMO
With the increasing number of asylum seekers in recent months, European dermatologists have been confronted with rising numbers of patients with formerly rare skin diseases and unusual infectious skin diseases that were previously scarcely observed at our latitude. Thorough examination of the patients medical history, including the routes of travel and the country of origin of the patients, detailed clinical and laboratory examinations, and - if necessary - referral to a special treatment center allow rapid and targeted treatment.
Assuntos
Dermatologia/tendências , Refugiados , Dermatopatias Bacterianas/diagnóstico , Dermatopatias Bacterianas/terapia , Dermatopatias Parasitárias/diagnóstico , Dermatopatias Parasitárias/terapia , Europa (Continente) , HumanosRESUMO
With the introduction of the latest class of biologic drugs targeting interleukin (IL)-23p19, three new, highly effective drugs can be used for the treatment of chronic plaque psoriasis. However, poorer skin improvement as well as higher rates of serious adverse events have been reported for patients under real-world conditions (outside clinical trials). This accounts especially for patients who have already been treated with biologic drugs. We therefore aimed to determine effectiveness and safety of IL-23p19 inhibitors in real-world patients by analysing data from the Psoriasis Registry Austria (PsoRA) in this observational, retrospective, multicentre cohort study. Data for 197 patients (52.3% biologic-non-naïve), who were treated with anti-IL-23p19 antibodies (127 guselkumab, 55 risankizumab and 15 tildrakizumab) for at least 3 months, were eligible for analysis. In general, biologic-non-naïve patients displayed a less favourable response to anti-IL-23 treatment as compared to biologic-naïve patients. However, after correction for previous biologic exposure, few differences in PASI improvement were detected among biologic-naïve and -non-naïve patients treated with different IL-23p19 inhibitors. This indicates that treatment effectiveness is not related to the class of the previously administered therapy in biologic-non-naïve patients. Therefore, IL-23p19 inhibitors represent a promising treatment alternative for patients who have not responded to previous biologics. However, as with other biologic agents (including IL-17 inhibitors), we did not observe an entirely satisfactory treatment response (i.e. PASI < 3 and/or PASI 75) to anti-IL-23 treatment in one out of four to five patients. Adverse events (mainly non-severe infections) were observed in 23 (11.7%) patients with no major differences regarding the administered IL-23 inhibitor or previous biologic exposure.
Assuntos
Produtos Biológicos , Doença Enxerto-Hospedeiro , Psoríase , Áustria/epidemiologia , Produtos Biológicos/uso terapêutico , Estudos de Coortes , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Interleucina-23 , Psoríase/tratamento farmacológico , Sistema de Registros , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Fumaric acid esters are considered efficacious and safe drugs for the treatment of psoriasis. Renal damage, caused either by acute renal injury or Fanconi syndrome, is a recognized side-effect of this therapy. OBJECTIVES: To investigate whether the measurement of urinary excretion of ß2-microglobulin, a marker of renal proximal tubular dysfunction, allows early detection of kidney damage before an increase in serum creatinine or significant proteinuria occurs. METHODS: Urinary ß2-microglobulin excretion was measured regularly in 23 patients undergoing fumaric acid ester therapy. RESULTS: Urinary ß2-microglobulin remained normal in all 10 male patients. Three (23%) out of 13 female patients experienced an increase in urinary ß2-microglobulin excretion. In two of these patients a sharp increase was observed in association with high doses. One further patient had moderately elevated levels on rather low doses of fumaric acid esters. After discontinuing treatment, urinary ß2-microglobulin levels returned to normal within a few weeks. CONCLUSION: Determination of urinary ß2-microglobulin possibly allows early detection of renal damage by fumaric acid esters. Female patients seem to be prone to this side-effect, especially when taking high doses.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Fumaratos/efeitos adversos , Microglobulina beta-2/urina , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/urina , Adulto , Biomarcadores/urina , Diagnóstico Precoce , Feminino , Fumaratos/uso terapêutico , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Psoríase/complicações , Psoríase/tratamento farmacológicoRESUMO
A sensitive, specific, accurate, and reproducible HPLC/MS-method for the simultaneous quantitative determination of niacin (NA) and its main metabolites niacinamide (NAM) and nicotinuric acid (NUR) in human plasma using chinolin-3-carboxylic acid as an internal standard was developed and validated according to international guidelines for method validation. All analytes and the internal standard were separated from acidified plasma by solid phase extraction. Afterwards the extracted samples were analyzed by HPLC/MS in the positive electrospray ionization mode (ESI) and selected ion monitoring (SIM). The total run time was 7 min between injections. The assay had a lower limit of quantification of 50.0 ng/mL for each analyte using 1 mL of plasma. The calibration curves were linear in the measured range between 50.0 and 750 ng/mL plasma. The overall precision and accuracy for all concentrations of quality controls and standards was better than 15%. No indications were found for possible instabilities of niacin, niacinamide and nicotinuric acid in plasma at -20 degrees C, in the extraction solvent or after repeated thawing/freezing cycles. In stabilities were observed in whole blood and in plasma at room temperature. The recovery of the extraction method ranged from 86 to 89% for the three analytes.
Assuntos
Niacina/sangue , Niacinamida/sangue , Ácidos Nicotínicos/sangue , Humanos , Niacina/química , Niacinamida/química , Ácidos Nicotínicos/químicaRESUMO
26 patients, aged between 53 and 72 years, with chronic myocardial insufficiency of different degrees, proved radiologically by an enlargement of the heart and a mean reduction of left ventricular ejection fraction by more than 50%, were subjected to 4 weeks of treatment with 3 x 60 drops/day Miroton, (Chemische) Werke Minden GmbH), a cardioactive glycoside mixture, following a washout phase of 4 weeks. The effect on end-diastolic volume (EDV) and left ventricular ejection fraction (LVEF) was recorded and calculated by ECG-triggered radionuclide angiography both before, and after 2 and 4 weeks of medication with Miroton. On therapy with Miroton the EDV decreased by 4% after 14 days and by 18% after 4 weeks (compared to the baseline value of 126.8 ml). In contrast to this, the LVEF increased to 47.2% after 14 days and to 56% after 4 weeks (baseline value 43.7%). The inverse relation between EDV and LVEF shows a positive inotropic influence on the myocardium which was more pronounced in the last 2 weeks of treatment than in the first 2 weeks.
Assuntos
Preparações Farmacêuticas/metabolismo , Cinética , MétodosRESUMO
This study examined the utility of a linear discriminant function to distinguish between students identified as learning disabled (LD) who had either been released from high school under codes suggestive of school dropout (n = 213) or graduation (n = 92). The discriminant function was comprised of six variables--student ethnicity, reading ability, family intactness, family socioeconomic status, school transfers, and school-initiated interruptions. The analysis determined that differences between the LD dropout sample and LD graduate sample were sufficient to allow for a discrimination between the groups. On the basis of group differences the discriminant function that was constructed correctly classified 83% of the school dropouts and 46% of the school graduates, for an overall 73% accuracy rate. Those factors contributing most to the function were the number of district-initiated interruptions, school transfers, and family intactness. Based on the findings, implications for school districts and future research are noted.
Assuntos
Educação Inclusiva , Deficiências da Aprendizagem/psicologia , Evasão Escolar/psicologia , Logro , Adolescente , Feminino , Humanos , Deficiências da Aprendizagem/diagnóstico , Masculino , Modelos Estatísticos , Fatores de Risco , Comportamento SocialAssuntos
Educação de Pessoa com Deficiência Intelectual , Destreza Motora , Percepção Visual , Adolescente , Criança , Feminino , Humanos , MasculinoAssuntos
Avaliação Educacional , Deficiências da Aprendizagem/diagnóstico , Pré-Escolar , Feminino , Humanos , Masculino , PsicometriaRESUMO
A new MS/MS assay for the quantitative determination of bromocriptine in body fluids is presented. The selective reagent gas in combination with the registration of selected, characteristic negative ions (SIM) after collision activated decomposition (CAD) in a Triple-Stage-Quaddrupole-mass spectrometer, provides an exceptional selective and sensitive assay in the low pg/ml range. The lower limit of detection was about 1 pg/ml (at optimal measuring conditions) and the calibration curve was linear in the range of 10-200 pg/ml. The coefficient of variation for the imprecision and inaccuracy data was typically below 10%; the recovery from plasma always exceeded 75%. The sample introduction to the mass spectrometer was done by a direct exposure probe (DEP). Thus, the method is well suited for the reliable, rapid processing of large sample numbers generated e.g. from clinical studies evaluating the pharmacokinetics and/or bioavailability/bioequivalence of different formulations or from drug monitoring/clinical response programs. The assay has been successfully approved in several clinical studies evaluating different bromocriptine preparations.
Assuntos
Bromocriptina/sangue , Disponibilidade Biológica , Bromocriptina/farmacocinética , Calibragem , Fenômenos Químicos , Química , Ergotamina , Humanos , Espectrometria de Massas/normas , Valor Preditivo dos Testes , Padrões de ReferênciaRESUMO
A demonstration program was conducted in which 54 innercity children classified as educable mentally retarded were selected on the basis of age, IQ, family income, race, and achievement scores. They were then placed into self-contained classrooms with two classes being taught by precision-teaching procedures and two classes being taught by the methods particular to their teachers. Tesults showed that a high percentage (60 percent) of the children taught by precision-teaching procedured were capable of acquiring the basic skills necessary for regular-class placement.
Assuntos
Educação de Pessoa com Deficiência Intelectual , Pobreza , Ensino/métodos , Criança , Feminino , Humanos , Deficiência Intelectual/reabilitação , Masculino , Instruções Programadas como Assunto , Leitura , Ensino de Recuperação , Teste de Stanford-Binet , População UrbanaRESUMO
An improved gas chromatographic-mass spectrometric chemical ionization assay for the quantitative determination of haloperidol in body fluids is presented. A fused silica, bonded phase capillary column, combined with negative ion chemical ionization (NICI), ammonia as a selective reagent gas and the monitoring of preselected characteristic ions (SIM), provide the combined sensitivity and selectivity necessary for reliable measurements in the low ng/ml range. The lower limit of detection was 0.1 ng/ml plasma and the calibration curve linear in the measured range of 0.1-5 ng/ml. In combination with the excellent imprecision and inaccuracy data and a recovery exceeding 90%, the method is very well suited for quantitative determinations of plasma samples generated during clinical studies, e.g. evaluating the pharmacokinetics and/or bioavailability/bioequivalence of haloperidol.
Assuntos
Haloperidol/sangue , Disponibilidade Biológica , Fenômenos Químicos , Química , Estabilidade de Medicamentos , Cromatografia Gasosa-Espectrometria de Massas , Haloperidol/farmacocinética , Humanos , Valor Preditivo dos TestesRESUMO
Depending on the very low therapeutic doses of clonidine and the resulting low blood levels (in the pg/ml range), for quantitative determinations in body fluids only methods of necessary selectivity as well as corresponding sensitivity can be employed successfully. Furthermore, the method should also be suited for the rapid processing of large sample numbers generated e.g. during clinical studies evaluating pharmacokinetics and/or the bioavailability/bioequivalence. Thus a gas chromatographic/mass spectrometric assay was developed employing fused-silica, bonded-phase capillary columns, chemical ionization with ammonia as a selective reagent gas in combination with the registration of preselected, characteristic negative ions (SIR, NICI) and a deuterated internal standard. Therefore, the method proves to be exceptionally selective and sensitive: a lower limit of detection of 10 pg/ml plasma is reached, the calibration curve is linear in the 25-1500 pg/ml range and the recovery from blood exceeds 90%. The assay has been successfully approved in several clinical studies, whereby especially the simple sample preparation led to very short times for analysis.