RESUMO
BACKGROUND: The Brief Symptom Inventory-18 (BSI-18) is a self-report questionnaire with three subscales, somatisation, anxiety, and depression, based on longer measures of distress. The present study proposes a shorter, nine-item version (BSI-9) of the BSI-18 as a brief screening tool for distress. METHODS: Confirmatory factor analyses and reliability and validity analyses were carried out using a representative sample of the German general population. Confirmatory factor analysis demonstrates a good model fit for the three-dimensional BSI-9. RESULTS: The total scale was found to have strong internal consistency (αCronbach = 0.87 for the global severity index). The internal consistency coefficients of the three-item subscales reflect the brevity of these scales (somatisation αCronbach = 0.72, depression α Cronbach = 0.79, anxiety αCronbach = 0.68). The subscales were found to be significantly related with subscales of the Patient Health Questionnaire-4 and Hopkins Symptom Checklist-25. LIMITATIONS: The present study used a limited number of distress measures, and a more recent dataset would be useful to provide a more current picture of the general population's distress levels. CONCLUSIONS: The BSI-9 provides a short, valid, and reliable screener for distress in the general population. Future work should examine its utility in clinical settings and different cultural contexts.
Assuntos
Ansiedade , Depressão , Psicometria , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Ansiedade/diagnóstico , Ansiedade/psicologia , Depressão/diagnóstico , Análise Fatorial , Alemanha , Escalas de Graduação Psiquiátrica/normas , Angústia Psicológica , Psicometria/instrumentação , Reprodutibilidade dos Testes , Autorrelato , Transtornos Somatoformes/diagnóstico , Transtornos Somatoformes/psicologia , Inquéritos e Questionários/normas , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: The choroid plexus (CP) produces and secretes most of the cerebrospinal fluid (CSF) of the central nervous system. The CP is suggested to be regulated by descending neurons and by circulating factors and is involved in the interaction between central and peripheral inflammation. Quantitative imaging has demonstrated volumetric CP changes in psychosis, schizophrenia and depression. This study histologically examines CP epithelial cell morphology in these illnesses to identify the biological source of such volumetric changes. METHODS: Formalin-fixed paraffin-embedded (FFPE) blocks were obtained bilaterally from the lateral ventricles of 13 cases of sex- and age-matched brains from each of schizophrenia (SZ) with psychosis, major depressive disorder (MDD) and matched controls (NPD). FFPE blocks were sectioned at 7 µm and routinely stained for H&E. Morphological analysis of 180 CP epithelia/case was conducted blindly on digital images collected at x600 magnification. Calcification was assessed in all CP regions manually. RESULTS: Analysis with a General Linear Model demonstrated a significant effect of diagnosis on somal width (p = 0.006, R2 = 0.33 R2(adj) = 0.25) demonstrating increased somal width in SZ without psychotic medication versus controls (p = 0.032), but not in medicated SZ cases. No effects were observed in calcification. DISCUSSION: The epithelial cells that were examined were attached to the CP fibrous surface, so width expansion describes the primary methods for these cells to expand with adherence to this surface in SZ. The interaction of antipsychotic medication and diagnosis demonstrates that this is an illness-specific change mediated through the DA-system with likely neuronal origin. CP alterations were not found in MDD where they are instead generally associated with heightened allostatic load that was unknown in this cohort.
Assuntos
Transtorno Depressivo Maior , Esquizofrenia , Humanos , Esquizofrenia/metabolismo , Plexo Corióideo/metabolismo , Transtorno Depressivo Maior/metabolismo , Encéfalo/metabolismo , Sistema Nervoso Central/metabolismoRESUMO
BACKGROUND: Swallowing therapy is commonly provided as a treatment to lessen the risk or severity of dysphagia secondary to radiotherapy (RT) for head and neck cancer (HNC); however, best practice is not yet established. This trial will compare the effectiveness of prophylactic (high and low intensity) versus reactive interventions for swallowing in patients with HNC undergoing RT. METHODS: This multi-site, international randomized clinical trial (RCT) will include 952 adult patients receiving radiotherapy for HNC and who are at high risk for post-RT dysphagia. Participants will be randomized to receive one of three interventions for swallowing during RT: RE-ACTIVE, started promptly if/when dysphagia is identified; PRO-ACTIVE EAT, low intensity prophylactic intervention started before RT commences; or, PRO-ACTIVE EAT+EXERCISE, high intensity prophylactic intervention also started before RT commences. We hypothesize that the PRO-ACTIVE therapies are more effective than late RE-ACTIVE therapy; and, that the more intensive PRO-ACTIVE (EAT + EXERCISE) is superior to the low intensive PRO-ACTIVE (EAT). The primary endpoint of effectiveness is duration of feeding tube dependency one year post radiation therapy, selected as a pragmatic outcome valued equally by diverse stakeholders (e.g., patients, caregivers and clinicians). Secondary outcomes will include objective measures of swallow physiology and function, pneumonia and weight loss, along with various patient-reported swallowing-related outcomes, such as quality of life, symptom burden, and self-efficacy. DISCUSSION: Dysphagia is a common and potentially life-threatening chronic toxicity of radiotherapy, and a priority issue for HNC survivors. Yet, the optimal timing and intensity of swallowing therapy provided by a speech-language pathologist is not known. With no clearly preferred strategy, current practice is fraught with substantial variation. The pragmatic PRO-ACTIVE trial aims to specifically address the decisional dilemma of when swallowing therapy should begin (i.e., before or after a swallowing problem develops). The critical impact of this dilemma is heightened by the growing number of young HNC patients in healthcare systems that need to allocate resources most effectively. The results of the PRO-ACTIVE trial will address the global uncertainty regarding best practice for dysphagia management in HNC patients receiving radiotherapy. TRIAL REGISTRATION: The protocol is registered with the US Patient Centered Outcomes Research Institute, and the PRO-ACTIVE trial was prospectively registered at ClinicalTrials.gov , under the identifier NCT03455608 ; First posted: Mar 6, 2018; Last verified: Jun 17, 2021. Protocol Version: 1.3 (January 27, 2020).
Assuntos
Transtornos de Deglutição/prevenção & controle , Deglutição , Neoplasias de Cabeça e Pescoço/radioterapia , Lesões por Radiação/complicações , Adulto , Tomada de Decisões , Deglutição/fisiologia , Deglutição/efeitos da radiação , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Nutrição Enteral/instrumentação , Humanos , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Pneumonite por Radiação , Autoeficácia , Método Simples-Cego , Fatores de Tempo , Redução de PesoRESUMO
BACKGROUND: Previous studies have shown conflicting results regarding the influence of cardiovascular risk-factors on venous thromboembolism. This study aimed to determine if these risk-factors, i.e. physical activity, smoking, hypertension, dyslipidaemia, and diabetes, were associated with the risk of venous thromboembolism, and to determine if these associations were confounded by BMI. METHODS: We used data from the E3N cohort study, a French prospective population-based study initiated in 1990, consisting of 98,995 women born between 1925 and 1950. From the women in the study we included those who did not have prevalent arterial disease or venous thromboembolism at baseline; thus 91,707 women were included in the study. Venous thromboembolism cases were self-reported during follow-up, and verified via specific mailings to medical practitioners or via drug reimbursements for anti-thrombotic medications. Hypertension, diabetes and dyslipidaemia were self-reported validated against drug reimbursements or specific questionnaires. Physical activity, and smoking were based on self-reports. Cox-models, adjusted for BMI and other potential risk-factors were used to determine hazard ratios for incident venous thromboembolism. RESULTS: During 1,897,960 person-years (PY), 1, 649 first incident episodes of thrombosis were identified at an incidence rate of 0.9 per 1000 PY. This included 505 cases of pulmonary embolism and 1144 cases of deep vein thrombosis with no evidence of pulmonary embolism. Hypertension, dyslipidaemia, diabetes, smoking and physical activity were not associated with the overall risk of thrombosis after adjustment for BMI. CONCLUSIONS: Traditional cardiovascular risk factors were not associated with the risk of venous thromboembolism after adjustment for BMI. Hypertension, dyslipidaemia and diabetes may not be risk-factors for venous thromboembolism.
RESUMO
Dyslipidaemia is a major risk factor for cardio-vascular disease, as it promotes atherosclerosis. While cross-sectional studies have identified higher serum cholesterol amongst individuals with the A blood group, there is less evidence from prospective studies whether this translates into a higher risk of dyslipidaemia that requires treatment, nor if this genetic factor interacts with smoking status. This study aimed to prospectively determine potential associations between smoking, ABO blood groups, and risk of incident dyslipidaemia requiring treatment, and to assess associations over strata of blood ABO group. We assessed associations between blood ABO group, smoking and dyslipidaemia in 74,206 women participating in the E3N cohort. We included women who did not have cardiovascular disease at baseline. Logistic regression was used to determine associations between ABO group, smoking and prevalent dyslipidaemia at baseline. Cox proportional hazard models were then used to determine if blood ABO group and smoking were associated with the risk of incident dyslipidaemia, amongst women free of dyslipidaemia at baseline. At baseline 28,281 women with prevalent dyslipidaemia were identified. Compared to the O-blood group, the non-O blood group was associated higher odds of with prevalent dyslipidaemia (ORnon-O = 1.09 [1.06: 1.13]). Amongst the women free of dyslipidaemia at baseline, 6041 incident cases of treated dyslipidaemia were identified during 454,951 person-years of follow-up. The non-O blood groups were associated with an increased risk of dyslipidaemia when compared to the O-group (HRnon-O = 1.16 [1.11: 1.22]), specifically the A blood-group (HRA = 1.18 [1.12: 1.25]). Current smokers were associated with an increased risk of incident dyslipidaemia (HR smokers = 1.27 [1.16: 1.37]), compared to never-smokers. No evidence for effect modification between smoking and ABO blood group was observed (p-effect modification = 0.45), although the highest risk was observed among AB blood group women who smoked (HR = 1.76 [1.22: 2.55]). In conclusion, the non-O blood groups, specifically the A group were associated with an increased risk of dyslipidaemia. Current smokers were associated with a 30% increased risk of dyslipidaemia. These results could aid in personalised approaches to the prevention of cardiovascular risk-factors.
Assuntos
Sistema ABO de Grupos Sanguíneos/efeitos adversos , Dislipidemias/etiologia , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Estudos de Coortes , Dislipidemias/epidemiologia , Feminino , França/epidemiologia , Humanos , Incidência , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Risco , Fatores de Risco , Fatores SexuaisRESUMO
BACKGROUND: Advanced General Practice Clinical Pharmacists (GPCPs) are expected to manage patients by undertaking clinical assessment then make safe, competent autonomous decisions. Simulation provides a safe learning environment to develop clinical skills, but is rarely used for postgraduate pharmacist development. AIM: Design and deliver innovative simulation teaching to support Advanced GPCPs in Scotland. SETTING: General Practice. DEVELOPMENT: Experienced clinical pharmacy educators designed a simulation day with ten scenarios based on general practice clinical presentations. Learning objectives were mapped to the National Advanced GPCP competency framework. IMPLEMENTATION: Simulation took place at the National Skills Education Hub, Louisa Jordan National Hospital, Glasgow, November 2020. Participants were briefed prior to each immersive simulation. Mannequins were used if clinical signs were expected to be identified on examination. Verbal and written feedback was given after each simulation. EVALUATION: Pre and post simulation questionnaires were developed. Increase in confidence and competence were reported in all areas pertaining to application of consultation and clinical skills. Qualitative comments from the participants regarding the training course were also favourable with respondents highlighting the value of the training, especially in terms of developing confidence via the real-time feedback. CONCLUSION: This innovative simulation evaluated as being of value to GPCPs in developing clinical confidence and competence when dealing with a variety of typical General Practice scenarios. Plans are underway to establish a Scottish Pharmacy Simulation Faculty which could support this training in each health board.
Assuntos
Medicina Geral , Serviço de Farmácia Hospitalar , Competência Clínica , Retroalimentação , Humanos , Farmacêuticos , EnsinoRESUMO
Abnormal muscle stiffness is a potential complication after injury and identifying interventions that modify muscle stiffness may be useful to promote recovery. The purpose of this study was to identify the short-term effects of dry needling (DN) on resting and contracted gastrocnemius muscle stiffness and strength of the triceps surae in individuals with latent myofascial trigger points (MTrPs). In this randomized controlled trial, 52 individuals received two DN treatment sessions to latent MTrPs and 50 individuals received two sham needling sessions. Resting and contracted muscle stiffness were assessed both at the treatment site and a standardized central site in the medial gastrocnemius head immediately post-treatment and one week after the last session. There were significant group by time interactions for resting muscle stiffness at the site of the MTrP (p = .03), but not at the central site (p = .29). Post-needling between group comparison indicated that the DN group had significantly lower resting muscle stiffness at the site of the MTrP than the sham group after adjusting for baseline differences. There were no significant between group differences in contracted muscle stiffness or muscle strength. Identifying strategies that can reduce aberrant muscle stiffness may help to guide management of individuals with neuromuscular pain-related conditions. Level of evidence: Therapy, level 2.
Assuntos
Agulhamento Seco/métodos , Contração Muscular/fisiologia , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Pontos-Gatilho/fisiologia , Adulto , Agulhamento Seco/tendências , Feminino , Humanos , Masculino , Medição da Dor/métodos , Medição da Dor/tendências , Estudos Prospectivos , Adulto JovemRESUMO
Neuroimaging biomarkers that can detect white matter (WM) pathology after mild traumatic brain injury (mTBI) and predict long-term outcome are needed to improve care and develop therapies. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to investigate WM microstructure cross-sectionally and longitudinally after mTBI and correlate these with neuropsychological performance. Cross-sectionally, early decreases of fractional anisotropy and increases of mean diffusivity corresponded to WM regions with elevated free water fraction on NODDI. This elevated free water was more extensive in the patient subgroup reporting more early postconcussive symptoms. The longer-term longitudinal WM changes consisted of declining neurite density on NODDI, suggesting axonal degeneration from diffuse axonal injury for which NODDI is more sensitive than DTI. Therefore, NODDI is a more sensitive and specific biomarker than DTI for WM microstructural changes due to mTBI that merits further study for mTBI diagnosis, prognosis, and treatment monitoring.
RESUMO
BACKGROUND: The COVID-19 pandemic has altered clinical practice and education in manual therapy globally. Social distancing has limited in-person care and changed health-care provision. Education in manual therapy has moved to online platforms with in-person instruction restricted. The global impact on the clinical practice of manual therapy and education has to date not been explored. METHODS: a questionnaire survey methodology was used. A sample of convenience of global leaders in manual therapy practice and education received an electronic link to two surveys: one on clinical practice and one on education. Contributors could complete one or both surveys. RESULTS: Twenty-five surveys were received on clinical practice and 23 on education in manual therapy, representing the six major continents. Global themes in clinical practice demonstrated a sudden and dramatic shift away from patient contact, with limited modifications to manual therapy in patient care currently adopted. Themes in education were of a major shift to online learning, development of new modes of student instruction including video-based assessment and virtual case-based instruction. CONCLUSION: The international perspectives provided demonstrate a major change in manual therapy practice and education globally. Various approaches have been taken in practice and education without a uniform approach being demonstrated.
Assuntos
Infecções por Coronavirus , Educação a Distância/tendências , Manipulações Musculoesqueléticas/educação , Manipulações Musculoesqueléticas/tendências , Pandemias , Pneumonia Viral , Betacoronavirus , COVID-19 , Humanos , Padrões de Prática Médica/tendências , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
PURPOSE: Recent studies have noted a degree of variance between the geometries segmented by different groups from 3D medical images that are used in computational fluid dynamics (CFD) simulations of patient-specific cardiovascular systems. The aim of this study was to determine if the applied sequence of magnetic resonance imaging (MRI) also introduced observable variance in CFD results. METHODS: Using a series of phantoms MR images of vessels of known diameter were assessed for the time-of-flight and multi-echo data image combination sequences. Following this, patient images of arterio-venous fistulas were acquired using the same sequences. Comparisons of geometry were made using the phantom and patient images, and of wall shear stress quantities using the CFD results from the patient images. RESULTS: Phantom images showed deviations in diameter between 0 and 15% between the sequences, depending on vessel diameter. Patient images showed different geometrical features such as narrowings that were not present on both sequences. Distributions of wall shear stress (WSS) quantities differed from simulations between the geometries obtained from the sequences. CONCLUSION: In conclusion, choosing different MRI sequences resulted in slightly different geometries of the same anatomy, which led to compounded errors in WSS quantities from CFD simulation.
Assuntos
Derivação Arteriovenosa Cirúrgica , Hemodinâmica , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Modelos Cardiovasculares , Imagem de Perfusão , Velocidade do Fluxo Sanguíneo , Humanos , Hidrodinâmica , Imageamento por Ressonância Magnética/instrumentação , Imagem de Perfusão/instrumentação , Imagens de Fantasmas , Valor Preditivo dos Testes , Fluxo Sanguíneo RegionalRESUMO
INTRODUCTION: Tissue surrounding the superficial inferior epigastric vein (SIEV) can be harvested for vascularised lymph node transfer (vLNT) for the treatment of lymphoedema. The aim of this study is to define the anatomical relationship of lymph nodes surrounding the SIEV. METHODS: Twenty-five fresh-frozen cadaveric groin specimens were harvested en bloc to the level of the deep fascia along the following anatomical boundaries, yielding quadrilateral tissue blocks: pubic tubercle (medial), anterior superior iliac spine (lateral), 5â¯cm superior and inferior to the inguinal ligament. The SIEV was marked at its entry point with the femoral vein. Specimens were oriented, secured and fixed in formaldehyde and analysed using longitudinal slices at 3â¯mm intervals. RESULTS: A total of 86 lymph nodes were identified. The average position of lymph nodes examined was 0.4â¯cm medial and 3.2â¯cm inferior to the mid-inguinal point. CLINICAL RELEVANCE: An improved understanding of the anatomical locations of lymph nodes surrounding the SIEV will allow a more purposeful harvest during vLNT, allowing a greater number of lymph nodes to be captured whilst limiting donor site morbidity.
Assuntos
Linfonodos/anatomia & histologia , Vasos Linfáticos/anatomia & histologia , Veias/anatomia & histologia , Abdome/anatomia & histologia , Abdome/irrigação sanguínea , Virilha/anatomia & histologia , Virilha/irrigação sanguínea , Humanos , Excisão de LinfonodoRESUMO
The investigation, management and follow-up of paediatric ureteropelvic junction obstruction is not standardized. The Young Pediatric Urology Committee of the European Society of Pediatric Urology interviewed five experts in the field on various aspects of management and compared this with published literature.
Assuntos
Gerenciamento Clínico , Laparoscopia/métodos , Procedimentos de Cirurgia Plástica/métodos , Obstrução Ureteral/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Criança , Humanos , Pelve Renal , Imageamento por Ressonância Magnética , Ultrassonografia , Obstrução Ureteral/diagnósticoRESUMO
The corpus callosum has become a key area of interest for researchers in severe mental illness. Disruptions in fractional anisotropy in the callosum have been reported in schizophrenia and major depressive disorder. No change has been reported in oligodendrocyte density and overall size of the callosum in either illness, suggesting that gross morphology is unchanged, but subtler organisational disruption may exist within this structure. Using high-resolution oil immersion microscopy, we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath; and using standard high-resolution light microscopy, we measured the density of myelinated axons. These measurements were made in the splenium of the corpus callosum. Measures were taken in the sagittal plane in the callosal splenium to contrast with the previous similar examination of the callosal genu. Cases of major depressive disorder had significantly decreased mean myelin cross-sectional area (p = 0.014) per axon in the splenium than in controls or schizophrenia groups. There was no significant change in the density of myelinated axons. The results suggest a clear decrease of myelin in the axons of the callosal splenium in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin. In contrast with increased myelin in the callosal genu, this result suggests a longitudinal change in callosal myelination in major depressive disorder not present in normal or schizophrenic brains.
Assuntos
Axônios/patologia , Corpo Caloso/patologia , Transtorno Depressivo Maior/patologia , Bainha de Mielina/patologia , Bancos de Tecidos , Adulto , Corpo Caloso/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Reported testicular loss rates following paediatric testicular torsion often reflect the surgical decision-making process, rather than long-term survival of the testes. OBJECTIVES: We aim to perform systematic analysis and meta-analysis to investigate testicular salvage rates and to assess predictors of long-term viability. STUDY DESIGN: Systematic review according to PRISMA guidelines was performed to investigate immediate and long-term (>12 months) testicular loss rates following torsion in the paediatric population. Literature search and study inclusion were performed by two investigators. A study quality score was derived and attributed to each study. Predictors of testicular loss were described. Proportions meta-analysis was performed with random effects modelling, and testing for heterogeneity. RESULTS: Twelve studies were includedm, 6 reporting early orchidectomy rates, and 6 reporting long-term outcomes. Study quality was generally low. DISCUSSION: The mean early testicular loss rate was 39%, whereas meta-analysis revealed late loss to approach 50%. Predictors of outcomes include prehospital symptom duration, location of presentation, transfer to a tertiary centre, social affluence and use of ultrasound prior to diagnosis or transfer. CONCLUSIONS: This study has shown a considerable late testicular loss rate, which must be relayed to families even after testicular salvage. Delay in time to presentation is consistently found to predict poor outcomes.
Assuntos
Torção do Cordão Espermático/cirurgia , Criança , Humanos , Masculino , Orquiectomia , Fatores de Tempo , Sobrevivência de Tecidos , Resultado do TratamentoRESUMO
Formation of the 3' ends of mature mRNAs requires recognition of the correct site within the last exon, cleavage of the nascent pre-mRNA, and, for most mRNAs, addition of a poly(A) tail. Several factors are involved in recognition of the correct 3'-end site. The cleavage stimulation factor (CstF) has three subunits, CstF-50 (gene symbol Cstf1), CstF-64 (Cstf2), and CstF-77 (Cstf3). Of these, CstF-64 is the RNA-binding subunit that interacts with the pre-mRNA downstream of the cleavage site. In male germ cells where CstF-64 is not expressed, a paralog, τCstF-64 (gene symbol Cstf2t) assumes its functions. Accordingly, Cstf2t knockout (Cstf2t-/- ) mice exhibit male infertility due to defective development of spermatocytes and spermatids. To discover differentially expressed genes responsive to τCstF-64, we performed RNA-Seq in seminiferous tubules from wild-type and Cstf2t-/- mice, and found that several histone and histone-like mRNAs were reduced in Cstf2t-/- mice. We further observed delayed accumulation of the testis-specific histone, H1fnt (formerly, H1t2 or Hanp1) in Cstf2t-/- mice. High-throughput sequence analysis of polyadenylation sites (A-seq) indicated reduced use of polyadenylation sites within a cluster downstream of H1fnt in knockout mice. However, high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP) was not consistent with a direct role of τCstF-64 in polyadenylation of H1fnt. These findings together suggest that the τCstF-64 may control other reproductive functions that are not directly linked to the formation of 3' ends of mature polyadenylated mRNAs during male germ cell formation.
Assuntos
Regulação da Expressão Gênica/fisiologia , Histonas/biossíntese , Espermatogênese/fisiologia , Espermatozoides/metabolismo , Animais , Fator Estimulador de Clivagem , Masculino , Camundongos , Camundongos Knockout , Poliadenilação/fisiologiaRESUMO
BACKGROUND: Hand eczema is a common inflammatory dermatosis that causes significant patient morbidity. Previous studies comparing psoralen-ultraviolet A (PUVA) with narrowband ultraviolet B (NB-UVB) have been small, nonrandomized and retrospective. OBJECTIVES: To conduct an observer-blinded randomized controlled pilot study using validated scoring criteria to compare immersion PUVA with NB-UVB for the treatment of chronic hand eczema unresponsive to topical steroids. METHODS: Sixty patients with hand eczema unresponsive to clobetasol propionate 0·05% were randomized to receive either immersion PUVA or NB-UVB twice weekly for 12 weeks with assessments at intervals of 4 weeks. The primary outcome measure was the proportion of patients achieving 'clear' or 'almost clear' Physician's Global Assessment (PGA) response at 12 weeks. Secondary outcome measures included assessment of the modified Total Lesion and Symptom Score (mTLSS) and the Dermatology Life Quality index (DLQI). RESULTS: In both treatment arms, 23 patients completed the 12-week assessment for the primary outcome measure. In the PUVA group, five patients achieved 'clear' and eight 'almost clear' [intention-to-treat (ITT) response rate 43%]. In the NB-UVB group, two achieved 'clear' and five 'almost clear' (ITT response rate 23%). For the secondary outcomes, median mTLSS scores were similar between groups at baseline (PUVA 9·5, NB-UVB 9) and at 12 weeks (PUVA 3, NB-UVB 4). Changes in DLQI were similar, with improvements in both groups. CONCLUSIONS: In this randomized pilot trial recruitment was challenging. After randomization, there were acceptable levels of compliance and safety in each treatment schedule, but lower levels of retention. Using validated scoring systems - PGA, mTLSS and DLQI - as measures of treatment response, the trial demonstrated that both PUVA and NB-UVB reduced the severity of chronic palmar hand eczema.
Assuntos
Eczema/tratamento farmacológico , Dermatoses da Mão/tratamento farmacológico , Terapia PUVA/métodos , Adulto , Idoso , Esquema de Medicação , Feminino , Ficusina/administração & dosagem , Ficusina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia PUVA/efeitos adversos , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/efeitos adversos , Projetos Piloto , Estudos Prospectivos , Método Simples-Cego , Raios Ultravioleta , Adulto JovemRESUMO
OBJECTIVES: To assess the safety of intra-articular (IA) autologous tolerogenic dendritic cells (tolDC) in patients with inflammatory arthritis and an inflamed knee; to assess the feasibility and acceptability of the approach and to assess potential effects on local and systemic disease activities. METHODS: An unblinded, randomised, controlled, dose escalation Phase I trial. TolDC were differentiated from CD14+ monocytes and loaded with autologous synovial fluid as a source of autoantigens. Cohorts of three participants received 1×106, 3×106 or 10×106 tolDC arthroscopically following saline irrigation of an inflamed (target) knee. Control participants received saline irrigation only. Primary outcome was flare of disease in the target knee within 5â days of treatment. Feasibility was assessed by successful tolDC manufacture and acceptability via patient questionnaire. Potential effects on disease activity were assessed by arthroscopic synovitis score, disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ). Immunomodulatory effects were sought in peripheral blood. RESULTS: There were no target knee flares within 5â days of treatment. At day 14, arthroscopic synovitis was present in all participants except for one who received 10×106 tolDC; a further participant in this cohort declined day 14 arthroscopy because symptoms had remitted; both remained stable throughout 91â days of observation. There were no trends in DAS28 or HAQ score or consistent immunomodulatory effects in peripheral blood. 9 of 10 manufactured products met quality control release criteria; acceptability of the protocol by participants was high. CONCLUSION: IA tolDC therapy appears safe, feasible and acceptable. Knee symptoms stabilised in two patients who received 10×106 tolDC but no systemic clinical or immunomodulatory effects were detectable. TRIAL REGISTRATION NUMBER: NCT01352858.