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2.
Burns ; 49(1): 42-54, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36202684

RESUMO

BACKGROUND: Early mobilization (EM) of intensive care (IC) patients is important but complex with facilitators and barriers. Compared to general IC patients, burn IC patients are more hyper-metabolic. They have extensive wounds, lengthy wound dressing changes, and repeated surgeries that may affect possibilities of EM. This study aimed to identify facilitators and barriers of EM in burn IC patients among all disciplines involved. Additionally, we assessed EM practices, i.e. when are which patients considered suitable for EM. METHODS: A survey was sent to 139 professionals involved in EM of burn IC patients (discipline groups: Intensivists, medical doctors, registered nurses, therapists). RESULTS: Response rate was 57 %. The majority found EM very important, yet different definitions were chosen. Perceived barriers mainly concerned patient-level factors, most frequently hemodynamic instability and excessive sedation followed by skin graft surgery, fatigue, and pain management. Most frequent barriers at the provider-level were limited staffing, safety concerns, and conflicting perceptions about the suitability of EM. At the institutional-level, we found no high barriers. Interdisciplinary variation on perceived barriers, when to initiate it, and permitted maximal activity were ascertained. CONCLUSION: Skin grafts and pain management were barriers of EM specific for burn care. Opinions on frequency, dosage and duration of EM varied widely. Improving interdisciplinary communication is key.


Assuntos
Queimaduras , Médicos , Humanos , Deambulação Precoce , Estado Terminal , Queimaduras/terapia , Inquéritos e Questionários
3.
Surg Oncol ; 44: 101841, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36087543

RESUMO

BACKGROUND: Ampullary adenocarcinoma (AAC) is a rare neoplasm which as a result is lacking specific treatment guidelines. This international survey study was performed to gain insight in the current daily practice of AAC. METHODS: Surgeons and medical oncologists, whom were members of the Dutch Pancreatic Cancer Group, International Study Group on Ampullary Cancer, International Hepato-Pancreato-Biliary Association, European and International Consortium on Minimally Invasive Pancreatic Surgery, or contributed to (peri)ampullary cancer research, were invited through email and newsletters between January and October 2021. RESULTS: Overall, 217 surgeons and medical oncologists completed the survey. Most of the respondents work in Europe (60%), and in a pancreatic expertise center (86%). The majority of respondents (87%) stated that the histological AAC subtype (e.g. intestinal vs. pancreatobiliary) was determined in the resection specimen. Neoadjuvant treatment for resectable disease was considered by 24% and adjuvant therapy by 90% of the respondents, with 80% of them choosing adjuvant chemotherapy alone. The formation of multidisciplinary teams, improvement in resection procedures, increased availability of chemotherapy regimens, and increased knowledge on tumor biology were considered as the most important developments in the last five years. The necessity for randomized controlled trials was mentioned by 50% of the respondents. CONCLUSIONS: This international survey highlights the existing variation in the management of patients with AAC, especially regarding the use of (neo)adjuvant therapy. More data from trials and international registries are needed to develop evidence-based guidelines on surgical and oncological management with the ultimate aim to improve outcomes for patients with AAC.


Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Neoplasias Duodenais , Oncologistas , Neoplasias Pancreáticas , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Neoplasias do Ducto Colédoco/patologia , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias Duodenais/patologia , Humanos , Neoplasias Pancreáticas/cirurgia , Inquéritos e Questionários , Neoplasias Pancreáticas
4.
Drugs Aging ; 39(9): 715-727, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35859228

RESUMO

BACKGROUND: Psoriasis is a common inflammatory disease in any age group, but also in older patients (≥ 65 years of age). Since older patients are often excluded from clinical trials, limited data specifically on this growing population are available, e.g. regarding the safety and performance of biological treatment. AIMS: We aimed to give insight into this specific population by comparing the drug survival and safety of biologics in older patients with that in younger patients. METHODS: In this real-world observational study, data from 3 academic and 15 non-academic centers in The Netherlands were extracted from the prospective BioCAPTURE registry. Biologics included in this study were tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-12/23, and IL-23 inhibitors. Patients were divided into two age groups: ≥ 65 years and < 65 years. The Charlson Comorbidity Index (CCI) was used to measure comorbid disease status, and all adverse events (AEs) that led to treatment discontinuation were classified according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. All AEs that led to treatment discontinuation were studied to check whether they could be classified as serious AEs (SAEs). Kaplan-Meier survival curves for overall 5-year drug survival and split according to reasons of discontinuation (ineffectiveness or AEs) were constructed. Cox regression models were used to correct for possible confounders and to investigate associations with drug survival in both age groups separately. Psoriasis Area and Severity Index (PASI) scores during the first 2 years of treatment and at the time of treatment discontinuation were assessed and compared between age groups. RESULTS: A total of 890 patients were included, of whom 102 (11.4%) were aged ≥ 65 years. Body mass index, sex, and distribution of biologic classes (e.g. TNFα, IL12/23) were not significantly different between the two age groups. A significantly higher CCI score was found in older patients, indicative of more comorbidity (p < 0.001). The 5-year ineffectiveness-related drug survival was lower for older patients (44.5% vs. 60.5%; p = 0.006), and the 5-year overall (≥ 65 years: 32.4% vs. < 65 years: 42.1%; p = 0.144) and AE-related (≥ 65 years: 82.1% vs. < 65 years: 79.5%; p = 0.913) drug survival was comparable between age groups. Of all AEs (n = 155) that led to discontinuation, 16 (10.3%) were reported as SAEs but these only occurred in younger patients. After correcting for confounders, the same trends were observed in the drug survival outcomes. Linear regression analyses on PASI scores showed no statistical differences at 6, 12, 18, and 24 months of treatment between age groups. CONCLUSIONS: This study in a substantial, well-defined, prospective cohort provides further support that the use of biologics in older patients seems well-tolerated and effective. Biologic discontinuation due to AEs did not occur more frequently in older patients. Older patients discontinued biologic treatment more often due to ineffectiveness, although no clear difference in PASI scores was observed. More real-world studies on physician- and patient-related factors in older patients are warranted.


Assuntos
Produtos Biológicos , Psoríase , Idoso , Produtos Biológicos/uso terapêutico , Humanos , Estudos Prospectivos , Psoríase/tratamento farmacológico , Sistema de Registros , Resultado do Tratamento
6.
J Eur Acad Dermatol Venereol ; 36 Suppl 1: 6-10, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34855246

RESUMO

The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing. A growing part of this patient group is formed by immunocompromised patients, for example organ-transplant recipients (OTR). Although over 90% of the cSCC show a relatively harmless clinical behaviour, there is also a chance of developing advanced cSCC and metastases. Locally advanced cSCC are defined as cSCC that have locally advanced progression and are no longer amenable to surgery or radiation therapy. Better understanding of the clinical behaviour of cSCC is essential to discriminate between low- and high-risk cSCC. Staging systems are important and have recently been improved. Genetic characterisation of SCC will likely become an important tool to help distinguish low and high-risk cSCC with an increased potential to metastasise in the near future. Available treatments for high-risk and advanced cSCC include surgery, radiotherapy, chemotherapy and targeted therapy with epidermal growth factor receptors inhibitors. Anti-PD-1 antibodies show promising results with response rates of up to 50% in both locally advanced and metastatic cSCC but, in its present form, is not suitable for OTR.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Humanos , Hospedeiro Imunocomprometido , Estadiamento de Neoplasias , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia
7.
J Eur Acad Dermatol Venereol ; 35(2): 281-317, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33547728

RESUMO

This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The second part of the guideline provides guidance for specific clinical and comorbid situations such as treating psoriasis vulgaris patient with concomitant psoriatic arthritis, concomitant inflammatory bowel disease, a history of malignancies or a history of depression or suicidal ideation. It further holds recommendations for concomitant diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or patients with a wish for a child in the near future. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.


Assuntos
Psoríase/complicações , Psoríase/terapia , Humanos , Psoríase/psicologia
8.
J Eur Acad Dermatol Venereol ; 35(1): 95-104, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32403174

RESUMO

BACKGROUND: Appropriate management and prevention of both under- and overtreatment in older skin cancer patients can be challenging. It could be helpful to incorporate frailty screening in dermato-oncology care, since frailty is associated with adverse health outcomes. OBJECTIVES: This study aimed to identify and prioritize the requirements a frailty screening tool (FST) should fulfil in dermato-oncology practice and to select the best existing FST(s) for this purpose. METHODS: A modified two-round Delphi procedure was performed among 50 Italian and Dutch specialists and patients to review and prioritize a list of potential FST requirements, using a 5-point Likert scale. Consensus was defined as a mean score of ≥4.0. A systematic literature search was performed to identify existing multidomain FSTs, which were then assessed on the requirements resulting from the modified Delphi procedure. RESULTS: Consensus was achieved on evaluation of comorbidities (4.3 ± 0.7), polypharmacy (4.0 ± 0.9) and cognition (4.1 ± 0.8). The FST should have appropriate measurement properties (4.0 ± 1.0), be quickly executed (4.2 ± 0.7), clinically relevant (4.3 ± 0.7), and both easily understandable (4.1 ± 1.2) and interpretable (4.3 ± 0.7). Of the 26 identified FSTs, four evaluated the content-related domains: the Geriatric-8 (G8), the modified Geriatric-8 (mG8), the Groningen Frailty Indicator (GFI) and the Senior Adult Oncology Program 2 (SAOP2) screening tool. Of these, the G8 was the most extensively studied FST, with the best psychometric properties and execution within 5 min. CONCLUSIONS: The G8 appears the most suitable FST for assessing frailty in older adults with skin cancer, although clinical studies assessing its use in a dermato-oncology population are needed to further assess whether or not frailty in this particular patient group is associated with relevant outcomes (e.g. complications and mortality), as seen in previous studies in other medical fields.


Assuntos
Fragilidade , Neoplasias , Idoso , Técnica Delphi , Idoso Fragilizado , Avaliação Geriátrica , Humanos , Oncologia
9.
Lung Cancer ; 148: 94-99, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32858338

RESUMO

OBJECTIVES: Radiological characteristics and radiomics signatures can aid in differentiation between small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). We investigated whether molecular subtypes of large cell neuroendocrine carcinoma (LCNEC), i.e. SCLC-like (with pRb loss) vs. NSCLC-like (with pRb expression), can be distinguished by imaging based on (1) imaging interpretation, (2) semantic features, and/or (3) a radiomics signature, designed to differentiate between SCLC and NSCLC. MATERIALS AND METHODS: Pulmonary oncologists and chest radiologists assessed chest CT-scans of 44 LCNEC patients for 'small cell-like' or 'non-small cell-like' appearance. The radiologists also scored semantic features of 50 LCNEC scans. Finally, a radiomics signature was trained on a dataset containing 48 SCLC and 76 NSCLC scans and validated on an external set of 58 SCLC and 40 NSCLC scans. This signature was applied on scans of 28 SCLC-like and 8 NSCLC-like LCNEC patients. RESULTS: Pulmonary oncologists and radiologists were unable to differentiate between molecular subtypes of LCNEC and no significant differences in semantic features were found. The area under the receiver operating characteristics curve of the radiomics signature in the validation set (SCLC vs. NSCLC) was 0.84 (95% confidence interval (CI) 0.77-0.92) and 0.58 (95% CI 0.29-0.86) in the LCNEC dataset (SCLC-like vs. NSCLC-like). CONCLUSION: LCNEC appears to have radiological characteristics of both SCLC and NSCLC, irrespective of pRb loss, compatible with the SCLC-like subtype. Imaging interpretation, semantic features and our radiomics signature designed to differentiate between SCLC and NSCLC were unable to separate molecular LCNEC subtypes, which underscores that LCNEC is a unique disease.


Assuntos
Carcinoma de Células Grandes , Carcinoma Neuroendócrino , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Carcinoma de Células Grandes/diagnóstico por imagem , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem
10.
Br J Dermatol ; 182(1): 55-66, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31120136

RESUMO

BACKGROUND: Rosacea assessment and therapy monitoring can be challenging to standardize, as most clinical evaluation systems are prone to interobserver variability and not always validated. Therefore, objective, reliable and preferably noninvasive measurement tools are needed. OBJECTIVES: To give insight into available noninvasive imaging techniques and biophysical methods in rosacea by performing a systematic review. METHODS: PubMed, Embase, Cochrane and Web of Science databases were searched until 1 September 2018 in accordance with PRISMA guidelines, to identify studies providing original data about objective noninvasive imaging and/or biophysical skin measurement techniques for diagnosis, assessing severity or therapy monitoring of adult patients with cutaneous facial rosacea. Risk of bias of included articles was assessed with the Cochrane Risk of Bias tool, Quality in Prognosis Studies tool, and the Newcastle-Ottawa Scale. RESULTS: A total of 78 studies were included, describing 14 imaging and biophysical methods. Widespread information about (sub)surface cutaneous morphology and functionality was obtained. Methodological study quality was relatively low and interstudy outcome variability was large. Several tools show promising value in research settings: for treatment follow-up Demodex mites are countable with reflectance confocal microscopy, spectrometry can quantify erythema, and rosacea severity could be objectified with skin hydration- and transepidermal water loss measurements. CONCLUSIONS: This systematic review describes the spectrum of noninvasive imaging and biophysical methods in rosacea assessment, giving multifaceted information about structure and properties of rosacea skin, especially useful for research purposes. Larger studies with good methodological quality are needed to create validated protocols for further implementation into research. What's already known about this topic? Rosacea is a chronic inflammatory skin disease with a variety of clinical manifestations. Most clinical evaluation systems are subjective, not always validated, and subsurface skin processes remain unnoticed. Currently, different types of noninvasive measurement tools are available for rosacea assessment and therapy monitoring, but a comprehensive overview is lacking. What does this study add? Seventy-eight publications were included, describing 14 imaging and biophysical tools, providing a wide range of information about rosacea skin morphology and functionality. Reflectance confocal microscopy and spectrometry are especially promising in therapy monitoring and skin barrier measurements for rosacea severity assessment. Larger studies with better methodological quality are needed to create validated protocols for implementation into research.


Assuntos
Rosácea , Adulto , Eritema , Humanos , Microscopia Confocal , Rosácea/diagnóstico , Pele
11.
Eur J Cancer ; 120: 107-113, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31514107

RESUMO

BACKGROUND: Muscle depletion negatively impacts treatment efficacy and survival rates in cancer. Prevention and timely treatment of muscle loss require prediction of patients at risk. We aimed to investigate the potential of skeletal muscle radiomic features to predict future muscle loss. METHODS: A total of 116 patients with stage IV non-small cell lung cancer included in a randomised controlled trial (NCT01171170) studying the effect of nitroglycerin added to paclitaxel-carboplatin-bevacizumab were enrolled. In this post hoc analysis, muscle cross-sectional area and radiomic features were extracted from computed tomography images obtained before initiation of chemotherapy and shortly after administration of the second cycle. For internal cross-validation, the cohort was randomly split in a training set and validation set 100 times. We used least absolute shrinkage and selection operator method to select features that were most significantly associated with muscle loss and an area under the curve (AUC) for model performance. RESULTS: Sixty-nine patients (59%) exhibited loss of skeletal muscle. One hundred ninety-three features were used to construct a prediction model for muscle loss. The average AUC was 0.49 (95% confidence interval [CI]: 0.36, 0.62). Differences in intensity and texture radiomic features over time were seen between patients with and without muscle loss. CONCLUSIONS: The present study shows that skeletal muscle radiomics did not predict future muscle loss during chemotherapy in non-small cell lung cancer. Differences in radiomic features over time might reflect myosteatosis. Future imaging analysis combined with muscle tissue analysis in patients and in experimental models is needed to unravel the biological processes linked to the radiomic features.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Músculo Esquelético/patologia , Tomografia Computadorizada por Raios X/métodos , Área Sob a Curva , Bevacizumab/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/efeitos dos fármacos , Estadiamento de Neoplasias , Nitroglicerina/administração & dosagem , Paclitaxel/administração & dosagem , Taxa de Sobrevida
12.
Lung Cancer ; 133: 130-135, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31200819

RESUMO

OBJECTIVES: To evaluate the relationship between early changes in muscle and adipose tissue during chemotherapy and overall survival (OS) in stage IV non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: In this post-hoc analysis of the first line NVALT12 trial (NCT01171170) in stage IV NSCLC, skeletal muscle (SM), radiation attenuation (RA), subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were assessed at the third lumbar level on CT-images obtained before initiation of chemotherapy and shortly after administration of the second cycle. The contribution of changes in different body compartments to overall survival was assessed. RESULTS: CT scans of 111 patients were included. Analysis of body composition changes between the baseline and the follow-up scan, revealed that overall SM cross sectional area (CSA), radiation attenuation and SAT CSA decreased respectively by -1.2 ± 2.9 cm2/m2 (p < 0.001), -0.7 ± 3.3 HU (p = 0.026) and -1.9 ± 8.7 cm2/m2 (p = 0.026), while no significant changes in VAT tissue were observed. Longitudinally, median OS was significantly shorter among patients losing SM compared to patients with preserved SM (9.4 versus 14.2 months; HR 1.9, 95% CI: 1.23, 2.79, p = 0.003). Multivariate analyses showed that proportional loss of muscle mass was associated with poor OS (HR 0.949, 95% CI: 0.915, 0.985, p = 0.006) independent from important clinical prognostic factors including WHO-PS, gender, age and Charlson comorbidity index. CONCLUSION: Early loss of SM during first line chemotherapy is a poor prognostic factor in stage IV NSCLC patients. Future studies have to reveal whether early supportive intervention guided by initial CT muscle response to chemotherapy can influence the wasting process and related mortality risk.


Assuntos
Tecido Adiposo/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Músculo Esquelético/patologia , Tomografia Computadorizada por Raios X/métodos , Tecido Adiposo/diagnóstico por imagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Atrofia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Metástase Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida
13.
J Autoimmun ; 101: 86-93, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31006523

RESUMO

BACKGROUND: Localized Scleroderma (LoS) encompasses a group of idiopathic skin conditions characterized by (sub)cutaneous inflammation and subsequent development of fibrosis. Currently, lack of accurate tools enabling disease activity assessment leads to suboptimal treatment approaches. OBJECTIVE: To investigate serum concentrations of cytokines and chemokines implicated in inflammation and angiogenesis in LoS and explore their potential to be utilized as biomarker of disease activity. Additionally, to investigate the implication of potential biomarkers in disease pathogenesis. METHODS: A 39-plex Luminex immuno-assay was performed in serum samples of 74 LoS and 22 Healthy Controls. The relation between a validated clinical measure of disease activity (mLoSSI) and serum analytes was investigated. Additionally, gene and protein expression were investigated in circulating cells and skin biopsies. RESULTS: From the total of 39, 10 analytes (CCL18, CXCL9, CXCL10, CXCL13, TNFRII, Galectin-9, TIE-1, sVCAM, IL-18, CCL19) were elevated in LoS serum. Cluster analysis of serum samples revealed CCL18 as most important analyte to discriminate between active and inactive disease. At individual patient level, CCL18 serum levels correlated strongest with mLoSSI-scores (rs = 0.4604, P < 0.0001) and in longitudinal measures CCL18 concentrations normalised with declining disease activity upon treatment initiation. Additionally, CCL18 was elevated in LoS serum, and not in (juvenile) dermatomyositis or spinal muscular atrophy. Importantly, CCL18 gene and protein expression was increased at the inflammatory border of cutaneous LoS lesions, with normal expression in unaffected skin and circulating immune cells. CONCLUSION: CCL18 is specific for disease activity in LoS thereby providing relevance as a biomarker for this debilitating disease.


Assuntos
Biomarcadores , Quimiocinas CC/metabolismo , Esclerodermia Localizada/metabolismo , Biópsia , Quimiocinas/metabolismo , Quimiocinas CC/sangue , Quimiocinas CC/genética , Citocinas/metabolismo , Suscetibilidade a Doenças , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Esclerodermia Localizada/diagnóstico , Esclerodermia Localizada/etiologia , Esclerodermia Localizada/terapia , Índice de Gravidade de Doença , Testes Cutâneos
14.
Br J Dermatol ; 178(1): 86-94, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28646581

RESUMO

BACKGROUND: Biologics are indicated for treating moderate-to-severe psoriasis. As the number of biologics registered for the treatment of psoriasis increases, so does the need for biomarkers to guide personalized therapeutic decisions. Genetic variants might serve as predictors for treatment response, a field of research known as pharmacogenetics. OBJECTIVES: To assess which genetic variants are associated with response to biologics in patients with psoriasis according to current literature. METHODS: A systematic search was performed in Embase, MEDLINE, the Cochrane Library and Web of Science. In total, 26 papers were included in this systematic review; 24 original studies and two meta-analyses. Quality was assessed using a predesigned form and risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: The majority of studies reported a candidate gene approach, focusing on polymorphisms in genes related to the therapeutic target or to psoriasis susceptibility. Studied populations were small and results were divergent, especially for studies investigating tumour necrosis factor inhibitors. The evidence for the role of HLA-Cw6 in ustekinumab efficacy shows minimal heterogeneity, with a higher response rate among patients who were positive for HLA-Cw6 reported across three of five studies. CONCLUSIONS: Pharmacogenetic studies in psoriasis have generated divergent results. Replication of findings in larger cohorts is required. Large-scale hypothesis-free searches for genetic biomarkers are needed to uncover the complete genetic background of outcomes for treatment with biologics.


Assuntos
Produtos Biológicos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Adalimumab/uso terapêutico , Estudos de Coortes , Etanercepte/uso terapêutico , Estudo de Associação Genômica Ampla , Humanos , Infliximab/uso terapêutico , Metanálise como Assunto , Testes Farmacogenômicos , Polimorfismo Genético , Psoríase/genética , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Fator de Necrose Tumoral alfa/genética , Ustekinumab/uso terapêutico
16.
Trials ; 18(1): 52, 2017 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-28148280

RESUMO

BACKGROUND: The introduction of anti-tumor necrosis factor medications has revolutionized the treatment of psoriasis with achievement of treatment goals (Psoriasis Area and Severity Index score 75, remission) that are not usually met with conventional systemics. Nevertheless, some patients continue to experience persistent disease activity or treatment failure over time. Strategies to optimize treatment outcomes include the use of concomitant methotrexate, which has demonstrated beneficial effects on pharmacokinetics and treatment efficacy in psoriasis and other inflammatory diseases. METHODS: This is an investigator-initiated, multicenter randomized controlled trial (RCT) designed to compare the combination treatment of adalimumab and methotrexate with adalimumab monotherapy in patients with psoriasis. The primary outcome is adalimumab drug survival at week 49. Other outcomes include improvement in disease severity and quality of life, tolerability, and safety. Moreover, anti-adalimumab antibodies and adalimumab serum concentrations will be measured and correlations between genotypes and clinical outcomes will be assessed. Patient recruitment started in March 2014. Up to now, 36 patients have been randomized. Many more patients have been (pre)screened. A total of 93 patients is desired to meet an adequate sample size. In our experience, the main limitation for recruitment is prior adalimumab therapy and intolerability or toxicity for methotrexate in the past. DISCUSSION: OPTIMAP is the first RCT to examine combination therapy with adalimumab and methotrexate in a psoriasis population. With data derived from this study we expect to provide valuable clinical data on long-term treatment outcomes. These data will be supported by assessment of the impact of concomitant methotrexate on adalimumab pharmacokinetics. Furthermore, the influence of several single nucleotide polymorphisms on adalimumab response will be analyzed in order to support the development of a more personalized approach for this targeted therapy. TRIAL REGISTRATION: NTR4499 . Registered on 7 April 2014.


Assuntos
Adalimumab/administração & dosagem , Produtos Biológicos/administração & dosagem , Imunossupressores/administração & dosagem , Metotrexato/administração & dosagem , Psoríase/tratamento farmacológico , Pele/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/efeitos adversos , Produtos Biológicos/efeitos adversos , Protocolos Clínicos , Quimioterapia Combinada , Humanos , Imunossupressores/efeitos adversos , Metotrexato/efeitos adversos , Países Baixos , Psoríase/diagnóstico , Psoríase/imunologia , Qualidade de Vida , Indução de Remissão , Projetos de Pesquisa , Índice de Gravidade de Doença , Método Simples-Cego , Pele/imunologia , Pele/patologia , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia
17.
Br J Dermatol ; 176(5): 1288-1296, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27564082

RESUMO

BACKGROUND: The effectiveness of biologics for psoriasis shows heterogeneity among patients. With pharmacogenetic markers, it might be possible to predict treatment response. OBJECTIVES: We aimed to test the association between genetic markers and the response to biologics in psoriasis (etanercept, adalimumab, ustekinumab) in a prospective cohort. METHODS: We investigated the copy number variation in the LCE3B and LCE3C genes, and eight single-nucleotide polymorphisms (SNPs) in HLA-C*06, CD84, IL12B, IL23R, TRAF3IP2, ERAP1, IFIH1 and TNFAIP3. The decrease in Psoriasis Area and Severity Index (PASI) was calculated as ∆PASI (absolute PASI decrease compared with baseline) and PASI 75 (proportion of patients with ≥ 75% improvement vs. baseline). Associations between genetic variants and treatment outcome were assessed using multivariable linear regression analysis (∆PASI corrected for baseline PASI, primary analysis) and Pearson's χ2 -test or Fisher's exact test (PASI 75, secondary analysis). RESULTS: We included 348 treatment episodes in 234 patients. Patients heterozygous (GA) for the SNP in CD84 (rs6427528) had a better ∆PASI response to etanercept after 3 months (P = 0·025) than the homozygous reference group (GG). In addition, patients heterozygous (CT) for the IL12B variant showed a better response (∆PASI) to ustekinumab (P = 0·017) than the reference group (CC). Patients homozygous (GG) for the SNP in TNFAIP3 showed a worse response (∆PASI) to ustekinumab (P = 0·031) than the reference group (TT). The associations with ustekinumab resulting from the primary analysis were not confirmed in the secondary (PASI 75) analysis. CONCLUSIONS: We demonstrated a strong association between etanercept use in psoriasis and variations in CD84, a gene that was previously found to be a predictor of response to etanercept in rheumatoid arthritis.


Assuntos
Produtos Biológicos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética , Psoríase/tratamento farmacológico , Adalimumab/uso terapêutico , Etanercepte/uso terapêutico , Feminino , Marcadores Genéticos , Humanos , Subunidade p40 da Interleucina-12/genética , Masculino , Pessoa de Meia-Idade , Psoríase/genética , Família de Moléculas de Sinalização da Ativação Linfocitária/genética , Resultado do Tratamento , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Ustekinumab/uso terapêutico
18.
J Eur Acad Dermatol Venereol ; 29(4): 752-60, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25229823

RESUMO

BACKGROUND: Concerns exist about a risk of non-melanoma skin cancer (NMSC) in psoriasis patients and rheumatoid arthritis (RA) patients treated with TNF-inhibitors. However, current data also show that in some psoriasis patients, NMSC is diagnosed relatively short after the start of TNF-inhibitors, which suggests that these NMSC can be explained by previous therapies instead of by TNF-inhibitor therapy. OBJECTIVE: To investigate whether there was a difference in time until first NMSC and the rate of NMSC between psoriasis and RA patients on TNF-inhibitors. METHODS: Time until first NMSC and the rate of NMSC were compared between psoriasis and RA patients from the same region treated with TNF-inhibitors and followed up for at least one year in prospective cohort studies, by using Cox regression and Poisson regression. Both analyses were corrected for confounders (age, gender, disease duration, prior NMSC, duration of anti-TNF and other systemic therapies). RESULTS: The NMSC risk was significantly higher in the psoriasis group [fully adjusted HR 6.0 (1.6-22.4 95%CI)] with a shorter time until first NMSC in psoriasis compared to RA. By Poisson regression, psoriasis patients had a 5.5 (2.2-13.4 95%CI) higher rate of NMSC. CONCLUSION: The time until first NMSC was significantly shorter and the rate of NMSC was significantly higher in psoriasis compared with RA. This indicates that disease-related factors like phototherapy may be important contributing factors to NMSC diagnosed in psoriasis patients treated with TNF-inhibitors.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Psoríase/tratamento farmacológico , Neoplasias Cutâneas/epidemiologia , Adalimumab/uso terapêutico , Adulto , Idoso , Etanercepte/uso terapêutico , Feminino , Seguimentos , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fototerapia , Fatores de Risco , Fatores de Tempo , Fator de Necrose Tumoral alfa/antagonistas & inibidores
19.
Pediatr Obes ; 10(2): 134-40, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24903612

RESUMO

OBJECTIVE: To investigate the association between home environmental determinants of fruit and vegetable consumption with childhood overweight separately for low, medium and high social economic status (SES) families. METHOD: A cross-sectional study was carried out in 2006 among 4072 children aged 4-13 years in the city of Zwolle, the Netherlands. Of these children, data were available on measured height and weight, and from a parental questionnaire, on sociodemographic characteristics and children's fruit and vegetables intake. Associations were studied using logistic regression analyses. RESULTS: Not eating the recommended amounts of vegetables daily was associated with overweight for children with a low SES background (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 0.66-2.07) and medium SES background (OR: 1.73; 95% CI: 1.20-2.49). Eating < 2 pieces of fruit daily was associated with a lower OR for overweight among children with a high SES background (OR: 0.66; 95% CI: 0.50-0.88). Determinants of eating vegetables < 7 d were: permission to take candy without asking, eating at the table < 7 d per week, eating a takeaway meal ≥ 1 d per week, eating a home cooked meal < 6 d per week and cooking together with caregiver less than 5 d per week. CONCLUSION: Interventions regarding vegetable consumption should be tailored to families with low and medium SES background. The most promising avenues for intervention seem to be (i) to prevent eating takeaway meals on a weekly basis and, (ii) to promote eating a home cooked meal at the table and (iii) to involve children in the cooking process. Interventions should support parents in making these home environmental changes.


Assuntos
Comportamento Alimentar/psicologia , Frutas , Comportamentos Relacionados com a Saúde , Pais/psicologia , Verduras , Criança , Pré-Escolar , Culinária , Estudos Transversais , Feminino , Humanos , Renda/estatística & dados numéricos , Masculino , Refeições , Países Baixos/epidemiologia , Sobrepeso , Poder Familiar , Pais/educação , Fatores de Risco , Meio Social , Fatores Socioeconômicos
20.
Br J Dermatol ; 171(5): 1189-96, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24807471

RESUMO

BACKGROUND: Drug survival is a marker for treatment success. To date, no analyses relating dermatological quality-of-life measures to drug survival have been published. OBJECTIVES: (i) To describe 1-year drug survival for adalimumab, etanercept and ustekinumab in a daily practice psoriasis cohort, and (ii) to introduce the concept of 'happy' drug survival, defined as Dermatology Life Quality Index (DLQI) ≤ 5 combined with being 'on drug' at a specific time point. METHODS: Data were extracted from a prospective registry. Drug survival was analysed using Kaplan-Meier estimates. 'Happy' drug survival was calculated, with data split into 'happy' (DLQI ≤ 5) vs. 'unhappy' (DLQI > 5) at baseline and months 3, 6, 9 and 12. RESULTS: 249 treatment episodes were included (101 adalimumab, 82 etanercept, 66 ustekinumab). The 1-year drug survival rates for ustekinumab, adalimumab and etanercept were 85%, 74% and 68%, respectively. Ustekinumab showed a better confounder-corrected drug survival vs. etanercept [hazard ratio (HR) 3·8, P = 0·02] and a trend towards better survival vs. adalimumab (HR 2·3, P = 0·1). At baseline, the majority (n = 115, 73%) was considered 'unhappy' and a minority 'happy' (n = 42, 27%) (ratio 'happy':'unhappy' was 1 : 2.7). The percentage of treatment episodes with 'happy' on-drug patients increased to 79% after 1 year. CONCLUSIONS: Ustekinumab showed a better overall drug survival than etanercept, and a trend towards a better overall drug survival than adalimumab. After 1 year, patients reported to be 'happy' in 79% of episodes and 'unhappy' in 21%. We introduced the new concept of 'happy' drug survival because the proportion of on-drug patients with good quality of life is an important indicator for treatment success.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Imunoglobulina G/uso terapêutico , Psoríase/tratamento farmacológico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab , Substituição de Medicamentos , Etanercepte , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Ustekinumab
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