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1.
J Am Acad Dermatol ; 82(2): 366-376, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31279015

RESUMO

BACKGROUND: A needs assessment for patients with hidradenitis suppurativa (HS) will support advancements in multidisciplinary care, treatment, research, advocacy, and philanthropy. OBJECTIVE: To evaluate unmet needs from the perspective of HS patients. METHODS: Prospective multinational survey of patients between October 2017 and July 2018. RESULTS: Before receiving a formal HS diagnosis, 63.7% (n = 827) of patients visited a physician ≥5 times. Mean delay in diagnosis was 10.2 ± 8.9 years. Patients experienced flare daily, weekly, or monthly in 23.0%, 29.8%, and 31.1%, respectively. Most (61.4% [n = 798]) rated recent HS-related pain as moderate or higher, and 4.5% described recent pain to be the worst possible. Access to dermatology was rated as difficult by 37.0% (n = 481). Patients reported visiting the emergency department and hospital ≥5 times for symptoms in 18.3% and 12.5%, respectively. An extreme impact on life was reported by 43.3% (n = 563), and 14.5% were disabled due to disease. Patients reported a high frequency of comorbidities, most commonly mood disorders. Patients were dissatisfied with medical or procedural treatments in 45.9% and 34.6%, respectively. LIMITATIONS: Data were self-reported. Patients with more severe disease may have been selected. CONCLUSION: HS patients have identified several critical unmet needs that will require stakeholder collaboration to meaningfully address.

2.
Biomolecules ; 9(9)2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438572

RESUMO

Hop cones (Humulus lupulus L.) have been used throughout history as an additive in beer brewing and as herbal supplements with medicinal and culinary properties. The objective of this study was to ascertain the effect of a range of concentrations of a supercritical CO2 extract of hops on the composition and metabolism of human gut bacterial communities using in vitro batch culture systems. Fermentations were conducted over 24 h using a mixed human fecal inoculum. Microbial metabolism was assessed by measuring organic acid production and microbial community alterations were determined by 16S rRNA gene sequencing. Butyrate, an important short chain fatty acid in maintaining colonic well-being, decreased at elevated concentrations of hops, which may partly be accounted for by the concomitant reduction of Eubacterium and Coprococcus, known butyrate-producing genera, and also the inhibition of Bifidobacterium, a beneficial organism that has a butyrogenic effect through metabolic cross-feeding with intestinal commensals. The hops compounds also caused dose-dependent increases in the potentially pathogenic Enterobacteriaceae and potentially beneficial Akkermansia. Thus, hops compounds had a significant impact on the structure of the bacterial consortium, which warrants further study including human clinical trials.

3.
J Am Acad Dermatol ; 81(1): 297-305, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30878565

RESUMO

The development of core outcome sets (COSs; ie, a minimum set of core outcomes that should be measured and reported in all trials or in clinical practice for a specific condition) in dermatology is increasing in pace. A total of 44 dermatology-related COS projects have been registered in the online Core Outcome Measures in Effectiveness Trials database (http://www.comet-initiative.org/studies/search) and include studies on 26 different skin diseases. With the increasing number of COSs in dermatology, care is needed to ensure the delivery of high-quality COSs that meet quality standards when using state-of-the-art methods. In 2015, the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN) was established. CS-COUSIN is an international, multidisciplinary working group aiming to improve the development and implementation of COSs in dermatology. CS-COUSIN has developed guidance on how to develop high-quality COSs for skin diseases and supports dermatology-specific COS initiatives. Currently, 17 COS development groups are affiliated with CS-COUSIN and following standardized COS development processes. To ensure successful uptake of COSs in dermatology, researchers, clinicians, systematic reviewers, guideline developers, and other stakeholders should use existing COSs in their work.


Assuntos
Ensaios Clínicos como Assunto , Dermatologia/organização & administração , Sistema de Registros , Dermatopatias/diagnóstico , Dermatopatias/terapia , Feminino , Saúde Global , Humanos , Masculino , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Projetos de Pesquisa
6.
Cochrane Database Syst Rev ; 12: CD011535, 2017 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-29271481

RESUMO

BACKGROUND: Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head to head, which is why we chose to conduct a network meta-analysis. OBJECTIVES: To compare the efficacy and safety of conventional systemic agents (acitretin, ciclosporin, fumaric acid esters, methotrexate), small molecules (apremilast, tofacitinib, ponesimod), anti-TNF alpha (etanercept, infliximab, adalimumab, certolizumab), anti-IL12/23 (ustekinumab), anti-IL17 (secukinumab, ixekizumab, brodalumab), anti-IL23 (guselkumab, tildrakizumab), and other biologics (alefacept, itolizumab) for patients with moderate to severe psoriasis and to provide a ranking of these treatments according to their efficacy and safety. SEARCH METHODS: We searched the following databases to December 2016: the Cochrane Skin Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We also searched five trials registers and the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) reports. We checked the reference lists of included and excluded studies for further references to relevant RCTs. We searched the trial results databases of a number of pharmaceutical companies and handsearched the conference proceedings of a number of dermatology meetings. SELECTION CRITERIA: Randomised controlled trials (RCTs) of systemic and biological treatments in adults (over 18 years of age) with moderate to severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate to severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent. DATA COLLECTION AND ANALYSIS: Three groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair-wise and network meta-analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the Psoriasis Area and Severity Index score (PASI) 90) and acceptability (the inverse of serious adverse effects). We assessed the certainty of the body of evidence from the NMA for the two primary outcomes, according to GRADE; we evaluated evidence as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing. MAIN RESULTS: We included 109 studies in our review (39,882 randomised participants, 68% men, all recruited from a hospital). The overall average age was 44 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo controlled (67%), 23% were head-to-head studies, and 10% were multi-armed studies with both an active comparator and placebo. We have assessed all treatments listed in the objectives (19 in total). In all, 86 trials were multicentric trials (two to 231 centres). All of the trials included in this review were limited to the induction phase (assessment at less than 24 weeks after randomisation); in fact, all trials included in the network meta-analysis were measured between 12 and 16 weeks after randomisation. We assessed the majority of studies (48/109) as being at high risk of bias; 38 were assessed as at an unclear risk, and 23, low risk.Network meta-analysis at class level showed that all of the interventions (conventional systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in terms of reaching PASI 90.In terms of reaching PASI 90, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents. Small molecules were associated with a higher chance of reaching PASI 90 compared to conventional systemic agents.At drug level, in terms of reaching PASI 90, all of the anti-IL17 agents and guselkumab (an anti-IL23 drug) were significantly more effective than the anti-TNF alpha agents infliximab, adalimumab, and etanercept, but not certolizumab. Ustekinumab was superior to etanercept. No clear difference was shown between infliximab, adalimumab, and etanercept. Only one trial assessed the efficacy of infliximab in this network; thus, these results have to be interpreted with caution. Tofacitinib was significantly superior to methotrexate, and no clear difference was shown between any of the other small molecules versus conventional treatments.Network meta-analysis also showed that ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab outperformed other drugs when compared to placebo in terms of reaching PASI 90: the most effective drug was ixekizumab (risk ratio (RR) 32.45, 95% confidence interval (CI) 23.61 to 44.60; Surface Under the Cumulative Ranking (SUCRA) = 94.3; high-certainty evidence), followed by secukinumab (RR 26.55, 95% CI 20.32 to 34.69; SUCRA = 86.5; high-certainty evidence), brodalumab (RR 25.45, 95% CI 18.74 to 34.57; SUCRA = 84.3; moderate-certainty evidence), guselkumab (RR 21.03, 95% CI 14.56 to 30.38; SUCRA = 77; moderate-certainty evidence), certolizumab (RR 24.58, 95% CI 3.46 to 174.73; SUCRA = 75.7; moderate-certainty evidence), and ustekinumab (RR 19.91, 95% CI 15.11 to 26.23; SUCRA = 72.6; high-certainty evidence).We found no significant difference between all of the interventions and the placebo regarding the risk of serious adverse effects (SAEs): the relative ranking strongly suggested that methotrexate was associated with the best safety profile regarding all of the SAEs (RR 0.23, 95% CI 0.05 to 0.99; SUCRA = 90.7; moderate-certainty evidence), followed by ciclosporin (RR 0.23, 95% CI 0.01 to 5.10; SUCRA = 78.2; very low-certainty evidence), certolizumab (RR 0.49, 95% CI 0.10 to 2.36; SUCRA = 70.9; moderate-certainty evidence), infliximab (RR 0.56, 95% CI 0.10 to 3.00; SUCRA = 64.4; very low-certainty evidence), alefacept (RR 0.72, 95% CI 0.34 to 1.55; SUCRA = 62.6; low-certainty evidence), and fumaric acid esters (RR 0.77, 95% CI 0.30 to 1.99; SUCRA = 57.7; very low-certainty evidence). Major adverse cardiac events, serious infections, or malignancies were reported in both the placebo and intervention groups. Nevertheless, the SAEs analyses were based on a very low number of events with low to very low certainty for just over half of the treatment estimates in total, moderate for the others. Thus, the results have to be considered with caution.Considering both efficacy (PASI 90 outcome) and acceptability (SAEs outcome), highly effective treatments also had more SAEs compared to the other treatments, and ustekinumab, infliximab, and certolizumab appeared to have the better trade-off between efficacy and acceptability.Regarding the other efficacy outcomes, PASI 75 and Physician Global Assessment (PGA) 0/1, the results were very similar to the results for PASI 90.Information on quality of life was often poorly reported and was absent for a third of the interventions. AUTHORS' CONCLUSIONS: Our review shows that compared to placebo, the biologics ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab are the best choices for achieving PASI 90 in people with moderate to severe psoriasis on the basis of moderate- to high-certainty evidence. At class level, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents, too. This NMA evidence is limited to induction therapy (outcomes were measured between 12 to 16 weeks after randomisation) and is not sufficiently relevant for a chronic disease. Moreover, low numbers of studies were found for some of the interventions, and the young age (mean age of 44 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice.Another major concern is that short-term trials provide scanty and sometimes poorly reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs. Methotrexate appeared to have the best safety profile, but as the evidence was of very low to moderate quality, we cannot be sure of the ranking. In order to provide long-term information on the safety of the treatments included in this review, it will be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies as well.In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve patients, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunossupressores/uso terapêutico , Meta-Análise em Rede , Psoríase/tratamento farmacológico , Adulto , Anticorpos Monoclonais/efeitos adversos , Doença Crônica , Humanos , Imunossupressores/efeitos adversos , Psoríase/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Fator de Necrose Tumoral alfa/antagonistas & inibidores
7.
Front Genet ; 8: 150, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29081791

RESUMO

The mechanisms that underlie the association between obesity and type 2 diabetes are not fully understood. Here, we investigated the role of the 3D genome organization in the pathogeneses of obesity and type-2 diabetes. We interpreted the combined and differential impacts of 196 diabetes and 390 obesity associated single nucleotide polymorphisms (SNPs) by integrating data on the genes with which they physically interact (as captured by Hi-C) and the functional [i.e., expression quantitative trait loci (eQTL)] outcomes associated with these interactions. We identified 861 spatially regulated genes (e.g., AP3S2, ELP5, SVIP, IRS1, FADS2, WFS1, RBM6, HORMAD1, PYROXD2), which are enriched in tissues (e.g., adipose, skeletal muscle, pancreas) and biological processes and canonical pathways (e.g., lipid metabolism, leptin, and glucose-insulin signaling pathways) that are important for the pathogenesis of type 2 diabetes and obesity. Our discovery-based approach also identifies enrichment for eQTL SNP-gene interactions in tissues that are not classically associated with diabetes or obesity. We propose that the combinatorial action of active obesity and diabetes spatial eQTL SNPs on their gene pairs within different tissues reduces the ability of these tissues to contribute to the maintenance of a healthy energy metabolism.

8.
Breast J ; 23(6): 747-749, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28892216

RESUMO

Breast cancer treatment involving ionizing radiation causes characteristic radiation dermatitis in the majority of patients. The DNA damaging effects of radiation can rarely predispose to primary inflammatory dermatoses, such as pemphigus vulgaris. In such cases, the disease presents with all the hallmarks of the primary dermatosis, but the eruption is limited to the field of irradiation and is often amenable to treatment. In contrast, occurrence of generalized pemphigus vulgaris in this setting may mean cancer recurrence. The mechanism by which radiotherapy induces localized disease remains unknown, but there is likely a loss of self-tolerance which maybe coupled to antigen exposure.


Assuntos
Neoplasias da Mama/radioterapia , Pênfigo/diagnóstico , Idoso de 80 Anos ou mais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Pênfigo/tratamento farmacológico , Pênfigo/etiologia , Pênfigo/patologia , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Radioterapia/efeitos adversos
9.
Am J Clin Nutr ; 106(3): 725-735, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28701300

RESUMO

Background: Activation of the ileal brake through the delivery of nutrients into the distal small intestine to promote satiety and suppress food intake provides a new target for weight loss. Evidence is limited, with support from naso-ileal lipid infusion studies.Objective: The objective of the study was to investigate whether glucose infused into the duodenum and ileum differentially alters appetite response, food intake, and secretion of satiety-related gastrointestinal peptides.Design: Fourteen healthy male participants were randomly assigned to a blinded 4-treatment crossover, with each treatment of single-day duration. On the day before the intervention (day 0), a 380-cm multilumen tube (1.75-mm diameter) with independent port access to the duodenum and ileum was inserted, and position was confirmed by X-ray. Subsequently (days 1-4), a standardized breakfast meal was followed midmorning by a 90-min infusion of isotonic glucose (15 g, 235 kJ) or saline to the duodenum or ileum. Appetite ratings were assessed with the use of visual analog scales (VASs), blood samples collected, and ad libitum energy intake (EI) measured at lunch, afternoon snack, and dinner.Results: Thirteen participants completed the 4 infusion days. There was a significant effect of nutrient infused and site (treatment × time, P < 0.05) such that glucose-to-ileum altered VAS-rated fullness, satisfaction, and thoughts of food compared with saline-to-ileum (Tukey's post hoc, P < 0.05); decreased ad libitum EI at lunch compared with glucose-to-duodenum [-22%, -988 ± 379 kJ (mean ± SEM), Tukey's post hoc, P < 0.05]; and increased glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) compared with all other treatments (Tukey's post hoc, P < 0.05).Conclusions: Macronutrient delivery to the proximal and distal small intestine elicits different outcomes. Glucose infusion to the ileum increased GLP-1 and PYY secretion, suppressed aspects of VAS-rated appetite, and decreased ad libitum EI at a subsequent meal. Although glucose to the duodenum also suppressed appetite ratings, eating behavior was not altered. This trial was registered at www.anzctr.org.au as ACTRN12612000429853.


Assuntos
Apetite/fisiologia , Duodeno/metabolismo , Ingestão de Energia/fisiologia , Hormônios Gastrointestinais/sangue , Glucose/administração & dosagem , Íleo/metabolismo , Resposta de Saciedade/fisiologia , Adolescente , Adulto , Ingestão de Alimentos , Nutrição Enteral , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Masculino , Peptídeo YY/sangue , Adulto Jovem
10.
JAMA Dermatol ; 153(5): 458-459, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28355440

RESUMO

Clinical Question: Which treatments have been shown to be effective in randomized clinical trials (RCTs) for hidradenitis suppurativa (HS) in adults? Bottom Line: There is high-quality evidence of benefit from adalimumab given weekly, while every other week dosing is ineffective, with reductions in Dermatology Life Quality Index (DLQI) scores compared with placebo of 2.8 points (95% CI, -3.7 to -2.0 points) and 1.6 points (95% CI, -3.9 to 0.6 points), respectively. Moderate-quality evidence suggests that infliximab is beneficial; RCT evidence for other interventions was lower in quality or absent, limiting further conclusions.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Hidradenite Supurativa/terapia , Qualidade de Vida , Adalimumab/administração & dosagem , Adalimumab/uso terapêutico , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Hidradenite Supurativa/patologia , Humanos , Infliximab/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
11.
Pharmacoeconomics ; 35(8): 805-815, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28176188

RESUMO

As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of adalimumab (AbbVie) to submit evidence on the clinical effectiveness and cost effectiveness of adalimumab for the treatment of moderate-to-severe hidradenitis suppurativa (HS). The appraisal assessed adalimumab as monotherapy in adult patients with an inadequate response to conventional systemic HS therapy. The School of Health and Related Research Technology Appraisal Group was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical effectiveness and cost effectiveness of the technology based on the company's submission to NICE. The evidence was mainly derived from three randomised controlled trials comparing adalimumab with placebo in adults with moderate-to-severe HS. The clinical-effectiveness review found that significantly more patients achieved a clinical response in the adalimumab groups than in the control groups but that the treatment effect varied between trials and there was uncertainty regarding its impact on a range of other relevant outcomes as well as long-term efficacy. The company's submitted Markov model assessed the incremental cost effectiveness of adalimumab versus standard care for the treatment of HS from the perspective of the UK NHS and Personal Social Services (PSS) over a lifetime horizon. The original submitted model, including a patient access scheme (PAS), suggested that the incremental cost-effectiveness ratio (ICER) for adalimumab versus standard care was expected to be £16,162 per quality-adjusted life-year (QALY) gained. Following a critique of the model, the ERG's preferred base case, which corrected programming errors and structural problems surrounding discontinuation rules and incorporated a lower unit cost for HS surgery, resulted in a probabilistic ICER of £29,725 per QALY gained. Based on additional analyses undertaken by the company and the ERG following the publication of the appraisal consultation document (ACD), the Appraisal Committee concluded that the maximum possible ICER for adalimumab compared with supportive care was between £28,500 and £33,200 per QALY gained but was likely to be lower. The Appraisal Committee recommended adalimumab (with the PAS) for the treatment of active moderate-to-severe HS in adults whose disease has not responded to conventional systemic therapy.


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Hidradenite Supurativa/tratamento farmacológico , Adalimumab/economia , Adulto , Anti-Inflamatórios/economia , Análise Custo-Benefício , Hidradenite Supurativa/economia , Hidradenite Supurativa/fisiopatologia , Humanos , Cadeias de Markov , Anos de Vida Ajustados por Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Avaliação da Tecnologia Biomédica/métodos
12.
J Asthma Allergy ; 10: 9-15, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28176912

RESUMO

Para-phenylenediamine (PPD) is the commonest and most well-known component of hair dyes. Oxidative hair dyes and dark henna temporary tattoos contain PPD. Individuals may be sensitized to PPD by temporary henna tattooing in addition to dyeing their hair. PPD allergy can cause severe reactions and may result in complications. In recent years, frequency of positive patch test reactions to PPD has been increasing. Cross-sensitization to other contact allergens may occur, in particular to other hair dye components. Hairdressers are at a high risk for PPD allergy and require counseling regarding techniques to minimize exposure and protective measures while handling hair dye. We focus this review on the current perspectives of diagnosis and management of PPD allergy.

13.
BMJ Open ; 7(2): e014733, 2017 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-28219961

RESUMO

INTRODUCTION: Randomised controlled trials (RCTs) should have well-defined primary and secondary outcomes to answer questions generated by the main hypotheses. However, for the chronic, inflammatory skin disease hidradenitis suppurativa (HS), the reported outcome measures are numerous and diverse. A recent systematic review found a total of 30 outcome measure instruments in 12 RCTs. This use of a broad range of outcome measures can increase difficulties in interpretation and comparison of results and may potentially obstruct appropriate evidence synthesis by causing reporting bias. One strategy for dealing with these problems is to develop a core outcome set (COS). A COS is a list of outcomes that are meant as mandatory and should be measured and reported in all clinical trials. The aim of this study is to develop a COS for the management of HS. METHOD AND ANALYSIS: An international steering group of researchers, clinicians and a patient research partner will guide the COS development. 6 stakeholder groups are involved: patients, dermatologists, surgeons, nurses, industry representatives and drug regulatory authorities. A 1:1 ratio of patients:healthcare professionals is aimed for. The initial list of candidate items will be obtained by combining three data sets: (1) a systematic review of the literature, (2) US and Danish qualitative interview studies involving patients with HS and (3) an online healthcare professional (HCP) item generation survey. To reach consensus on the COS, 4 anonymous online Delphi rounds are then planned together with 2 face-to-face consensus meetings (1 in Europe and 1 in the USA) to ensure global representation. ETHICS AND DISSEMINATION: The study will be performed according to the Helsinki declaration. All results from the study, including inconclusive or negative results, will be published in peer-reviewed indexed journals. The study will involve different stakeholder groups to ensure that the developed COS will be suitable and well accepted.


Assuntos
Consenso , Hidradenite Supurativa/terapia , Técnica Delfos , Humanos , Pesquisa Qualitativa , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Índice de Gravidade de Doença , Inquéritos e Questionários , Revisão Sistemática como Assunto , Resultado do Tratamento
14.
Clin Med (Lond) ; 16(1): 70-3, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26833521

RESUMO

Hidradenitis suppurativa (HS) is a chronic, painful skin disease characterised by recurrent inflammatory lesions in flexural locations such as the axillae, groins and perineum. The papules, nodules and abscesses may discharge blood-stained pus which, combined with pain, results in marked quality-of-life reduction. Sinus tracts and scarring may also result. Onset of HS is typically in the second to fourth decades and it affects about 1% of young European adults. There are links with smoking and obesity and an autosomal dominant pattern of inheritance is reported by one-third of patients. Medical management escalates from topical antimicrobials to oral tetracyclines, a combination of clindamycin and rifampicin typically given for 10 weeks, oral disease modifiers, and anti-tumour necrosis factor-alpha therapies. Excision of individual lesions has high recurrence rates which can be minimised by wider excisions, at the expense of longer healing times. Treatment of pain is a relatively neglected aspect of therapy.


Assuntos
Hidradenite Supurativa , Adulto , Axila/patologia , Feminino , Hidradenite Supurativa/epidemiologia , Hidradenite Supurativa/etiologia , Hidradenite Supurativa/fisiopatologia , Hidradenite Supurativa/terapia , Humanos , Masculino , Obesidade , Manejo da Dor , Qualidade de Vida , Fatores de Risco , Pele/patologia , Fumar
15.
Dermatol Clin ; 34(1): 23-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26617354

RESUMO

A family history of hidradenitis suppurativa (HS) is reported by about one-third of patients, and the pattern of inheritance suggests a single gene disorder inherited as an autosomal dominant trait. Several γ-secretase gene mutations were identified in 6 Han Chinese families with multiple affected family members. Several of the Han Chinese patients had a severe disease phenotype, with involvement of nonflexural skin locations such as the back and chest. These findings have been repeated in other populations, but γ-secretase mutations have been found only in a minority of patients with HS.


Assuntos
Secretases da Proteína Precursora do Amiloide/genética , Hidradenite Supurativa/genética , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Heterozigoto , Humanos , Mutação , Receptores Notch , Transdução de Sinais
16.
Cochrane Database Syst Rev ; (10): CD010081, 2015 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-26443004

RESUMO

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterised by recurrent painful boils in flexural sites, such as the axillae and groin, that affects about 1% of the population, with onset in early adulthood. OBJECTIVES: To assess the effects of interventions for HS in people of all ages. SEARCH METHODS: We searched the following databases up to 13 August 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 7, 2015), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We also searched five trials registers and handsearched the conference proceedings of eight dermatology meetings. We checked the reference lists of included and excluded studies for further references to relevant trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) of all interventions for hidradenitis suppurativa. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility and methodological quality and performed data extraction. Our primary outcomes were quality of life, measured by a validated dermatology-specific scale, and adverse effects of the interventions. MAIN RESULTS: Twelve trials, with 615 participants, met our inclusion criteria. The median number of participants in each trial was 27, and median trial duration was 16 weeks. The included studies were conducted over a 32-year time period, from 1983 to 2015. A single RCT that was underpowered to detect clinically meaningful differences investigated most interventions.There were four trials of anti-TNF-α (tumour necrosis factor-alpha) therapies, which included etanercept, infliximab, and adalimumab. Adalimumab 40 mg weekly improved the Dermatology Life Quality Index (DLQI) score in participants with moderate to severe HS by 4.0 points relative to placebo (95% confidence interval (CI) -6.5 to -1.5 points), an effect size approximately equal to the DLQI minimal clinically important difference. We reduced the evidence quality to 'moderate' because the effect size was based on the results of only one study. In a meta-analysis of two studies with 124 participants, standard dose adalimumab 40 mg every other week was ineffective compared with placebo (moderate quality evidence). In a smaller study of 38 participants, of whom only 33 provided efficacy data, infliximab 5 mg/kg treatment improved DLQI by 8.4 DLQI points after eight weeks. Etanercept 50 mg twice weekly was well tolerated but ineffective.In a RCT of 200 participants, no difference was found in surgical complications (week one: risk ratio (RR) 0.78, 95% CI 0.58 to 1.05, moderate quality evidence) or risk of recurrence (after three months: RR 0.96, 95% CI 0.68 to 1.34, moderate quality evidence) in those randomised to receive a gentamicin-collagen sponge prior to primary closure compared with primary closure alone.RCTs of other interventions, including topical clindamycin 1% solution; oral tetracycline; oral ethinylestradiol 50 mcg with either cyproterone acetate 50 mg or norgestrel 500 mcg; intense pulsed light; neodymium-doped yttrium aluminium garnet (Nd:YAG) laser; methylene blue gel photodynamic therapy; and staphage lysate, were relatively small studies, preventing firm conclusions due to imprecision. AUTHORS' CONCLUSIONS: Many knowledge gaps exist in RCT evidence for HS. Moderate quality evidence exists for adalimumab, which improves DLQI score when 40 mg is given weekly, twice the standard psoriasis dose. However, the 95% confidence interval includes an effect size of only 1.5 DLQI points, which may not be clinically relevant, and the safety profile of weekly dosing has not been fully established. Infliximab also improves quality of life, based on moderate quality evidence.More RCTs are needed in most areas of HS care, particularly oral treatments and the type and timing of surgical procedures. Outcomes should be validated, ideally, including a minimal clinically important difference for HS.


Assuntos
Hidradenite Supurativa/terapia , Adulto , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Feminino , Humanos , Terapia de Luz Pulsada Intensa/métodos , Terapia a Laser/métodos , Masculino , Fotoquimioterapia/métodos , Fototerapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa/antagonistas & inibidores
17.
Nutr J ; 14: 96, 2015 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-26370656

RESUMO

BACKGROUND: There is recent evidence that glucose delivered to the distal small intestine (SI) may stimulate the ileal brake and inhibit appetite. High polyphenolic grape extract (PGE) has been shown to inhibit α-amylase and α-glucosidase activity, two key enzymes required for starch digestion, in vitro. It is hypothesised to slow digestion and absorption of starch in the proximal SI such that glucose may be delivered distally into the ileum and suppress appetite. This study investigated the safety and efficacy of a PGE supplement, delivered within a capsule and consumed with a high-starch breakfast, on appetite ratings and ad libitum energy intake (EI) at a subsequent lunch meal. METHODS: Twenty healthy, non-obese (BMI 18-28 kg/m(2)) male volunteers participated in a randomised, double blind, placebo controlled, three arm, cross-over study. Participants were administered (i) low dose PGE500 (500 mg), (ii) high dose PGE1500 (1500 mg), and (iii) matched placebo with a 2 MJ high-starch breakfast (white bread); followed 3 h later by a single item buffet-style lunch meal (pasta and meat sauce). Outcome variables were feelings of hunger, fullness, prospective thoughts of food (TOF) and satisfaction assessed using visual analogue scales (VAS); and ad lib energy and macronutrient intake at the lunch meal. RESULTS: There was no detectable effect of PGE500 or PGE1500 compared with placebo (all, time*supplement interaction, P > 0.05) on VAS-assessed hunger, fullness, TOF or satisfaction. There was also no evidence that PGE significantly altered ad lib energy or macronutrient intake at the lunch meal relative to placebo (P > 0.05). EI following PGE500 was +164 kJ higher than placebo (+5.3%, P > 0.05); and EI following PGE1500 was -51 kJ lower than placebo (-1.7%, P > 0.05). CONCLUSIONS: Whilst well tolerated, there was no evidence that encapsulated low dose PGE500 or high dose PGE1500 consumed with a high starch breakfast meal altered postprandial hunger, fullness, TOF or satisfaction relative to a matched placebo. Nor was there evidence that either dose altered ad lib energy or macronutrient intake at an outcome meal. TRIAL REGISTRATION: ACTRN12614000041651.


Assuntos
Apetite/efeitos dos fármacos , Extratos Vegetais/farmacologia , Período Pós-Prandial , Vitis/química , Adolescente , Adulto , Índice de Massa Corporal , Desjejum , Estudos Cross-Over , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Ingestão de Energia , Voluntários Saudáveis , Humanos , Fome , Almoço , Masculino , Pessoa de Meia-Idade , Polifenóis/farmacologia , Adulto Jovem , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo
18.
Cochrane Database Syst Rev ; (8): CD010497, 2015 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-26258748

RESUMO

BACKGROUND: Psoriasis is a chronic inflammatory skin condition that can markedly reduce life quality. Several systemic therapies exist for moderate to severe psoriasis, including oral fumaric acid esters (FAE). These contain dimethyl fumarate (DMF), the main active ingredient, and monoethyl fumarate. FAE are licensed for psoriasis in Germany but used off-licence in many countries. OBJECTIVES: To assess the effects and safety of oral fumaric acid esters for psoriasis. SEARCH METHODS: We searched the following databases up to 7 May 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 4, 2015), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials. We handsearched six conference proceedings that were not already included in the Cochrane Skin Group Specialised Register. SELECTION CRITERIA: Randomised controlled trials (RCTs) of FAE, including DMF monotherapy, in individuals of any age and sex with a clinical diagnosis of psoriasis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Primary outcomes were improvement in Psoriasis Area and Severity Index (PASI) score and the proportion of participants discontinuing treatment due to adverse effects. MAIN RESULTS: We included 6 studies (2 full reports, 2 abstracts, 1 brief communication, and 1 letter), with a total of 544 participants. Risk of bias was unclear in several studies because of insufficient reporting. Five studies compared FAE with placebo, and one study compared FAE with methotrexate. All studies reported data at 12 to 16 weeks, and we identified no longer-term studies. When FAE were compared with placebo, we could not perform meta-analysis for the primary outcome of PASI score because the three studies that assessed this outcome reported the data differently, although all studies reported a significant reduction in PASI scores with FAE. Only 1 small study designed for psoriatic arthritis reported on the other primary outcome of participants discontinuing treatment due to adverse effects (2 of 13 participants on FAE compared with none of the 14 participants on placebo; risk ratio (RR) 5.36, 95% confidence interval (CI) 0.28 to 102.1; 27 participants; very low-quality evidence). However, these findings are uncertain due to indirectness and a very wide confidence interval. Two studies, containing 247 participants and both only reported as abstracts, allowed meta-analysis for PASI 50, which showed superiority of FAE over placebo (RR 4.55, 95% CI 2.80 to 7.40; low-quality evidence), with a combined PASI 50 of 64% in those given FAE compared with a PASI 50 of 14% for those on placebo, representing a number needed to treat to benefit of 2. The same studies reported more participants achieving PASI 75 with FAE, but we did not pool the data because of significant heterogeneity; none of the studies measured PASI 90. One study reported significant improvement in participants' quality of life (QoL) with FAE, measured with Skindex-29. However, we could not compute the mean difference because of insufficient reporting in the abstract. More participants experienced adverse effects, mainly gastrointestinal disturbance and flushing, on FAE (RR 4.72, 95% CI 2.45 to 9.08; 1 study, 99 participants; moderate-quality evidence), affecting 76% of participants given FAE and 16% of the placebo group (representing a number needed to treat to harm of 2). The other studies reported similar findings or did not report adverse effects fully.One study of 54 participants compared methotrexate (MTX) with FAE. PASI score at follow-up showed superiority of MTX (mean Difference (MD) 3.80, 95% CI 0.68 to 6.92; 51 participants; very low-quality evidence), but the difference was not significant after adjustment for baseline disease severity. The difference between groups for the proportion of participants who discontinued treatment due to adverse effects was uncertain because of imprecision (RR 0.19, 95% CI 0.02 to 1.53; 1 study, 51 participants; very low-quality evidence). Overall, the number of participants experiencing common nuisance adverse effects was not significantly different between the 2 groups, with 89% of the FAE group affected compared with 100% of the MTX group (RR 0.89, 95% CI 0.77 to 1.03; 54 participants; very low-quality evidence). Flushing was more frequent in those on FAE, with 13 out of 27 participants affected compared with 2 out of 27 given MTX. There was no significant difference in the number of participants who attained PASI 50, 75, and 90 in the 2 groups (very low-quality evidence) whereas this study did not measure the effect of treatments on QoL. The included studies reported no serious adverse effects of FAE and were too small and of limited duration to provide evidence about rare or delayed effects. AUTHORS' CONCLUSIONS: Evidence suggests that FAE are superior to placebo and possibly similar in efficacy to MTX for psoriasis; however, the evidence provided in this review was limited, and it must be noted that four out of six included studies were abstracts or brief reports, restricting study reporting. FAE are associated with nuisance adverse effects, including flushing and gastrointestinal disturbance, but short-term studies reported no serious adverse effects.


Assuntos
Fumaratos/administração & dosagem , Psoríase/tratamento farmacológico , Administração Oral , Artrite Psoriásica/tratamento farmacológico , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Fumaratos/efeitos adversos , Humanos , Metotrexato/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença
19.
BMC Dermatol ; 15: 4, 2015 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-25887502

RESUMO

BACKGROUND: Eczema (syn. Atopic Eczema or Atopic Dermatitis) is a chronic, relapsing, itchy skin condition which probably results from a combination of genetic and environmental factors. The Global Resource of EczemA Trials (GREAT) is a collection of records of randomised controlled trials (RCTs) for eczema treatment produced from a highly sensitive search of six reference databases. We sought to assess the sensitivity of the GREAT database as a tool to save future researchers repeating extensive bibliographic searches. METHODS: All Cochrane systematic review on treatments for eczema and five non-Cochrane systematic reviews on eczema were identified as a reference set to assess the utility of the GREAT database in identifying randomised controlled trials (RCTs). RCTs included in the systematic reviews were checked for inclusion in the GREAT database by two independent authors. A third author resolved any disagreements. RESULTS: Five Cochrane and six non-Cochrane systematic reviews containing a total of 105 RCTs of eczema treatments were included. Of these, 95 fitted the inclusion criteria for the GREAT database and 88 were published from 2000 onwards. Of the 88 eligible studies, 92% were found in the GREAT database. Seven trials were not included in the GREAT database - two of these were reported within a review paper and one as an abstract with no trial results. CONCLUSIONS: The sensitivity of the GREAT database for trials from 2000 onwards was high (75/88 trials, 94%). Sensitivity for the period prior to 2000 was less sensitive, due to differences in how the trials were identified prior to this time. 'Dual' filtering for new records has recently become part of the GREAT database methodology and should further improve the sensitivity of the database in time. The GREAT database can be considered as a primary source for future systematic reviews including randomised controlled trials of eczema treatments, but searches should be supplemented by checking reference lists for eligible trials, searching trial registries and contacting pharmaceutical companies for unpublished studies.


Assuntos
Bases de Dados Factuais , Dermatite Atópica/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Bases de Dados Bibliográficas , Humanos , Literatura de Revisão como Assunto , Sensibilidade e Especificidade
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