ABSTRACT
The slogan Undetectable equals Untransmittable (U = U) communicates that people living with HIV (PLHIV) who are on antiretroviral therapy (ART) will not transmit HIV to their sexual partners. We describe awareness of U = U among sexual and gender minorities (SGM) living in Brazil, Mexico, and Peru by self-reported HIV status (PLHIV, negative, unknown) during 2021 using an online survey. We estimated two models using Poisson regression for each population group: Model A including socio-demographic factors (country, gender, age, race, education, and income), and then Model B including taking ART (for PLHIV) or risk behavior, ever-taking PrEP, and HIV risk perception (for HIV-negative or of unknown HIV status). A total of 21,590 respondents were included (Brazil: 61%, Mexico: 30%, Peru: 9%). Among HIV-negative (74%) and unknown status (12%), 13% ever used PrEP. Among PLHIV (13%), 93% reported current use of ART. Awareness of U = U was 89% in both Brazil and Mexico, which was higher than in Peru 64%. Awareness of U = U was higher among PLHIV (96%) than HIV-negative (88%) and HIV-unknown (70%). In multivariate models, PLHIV with lower education were less aware of U = U, while those taking ART were more aware. Among HIV-negative, non-cisgender, lower income, and those with lower education had lower awareness of U = U, while individuals ever using PrEP had higher awareness. In conclusion, awareness of U = U varied by HIV status, socio-demographic characteristics, and HIV risk behavior. The concept of U = U should be disseminated through educational strategies and include a focus on SGM to combat HIV stigma.
RESUMEN: Indetectable = Intransmisible (I = I) comunica que las personas que viven con VIH (PVVIH) y reciben tratamiento antirretroviral (TAR) no transmitirán el VIH a sus parejas sexuales. En este estudio, describimos la concienciación sobre I = I entre las minorías sexuales y de género (MSG) de Brasil, México y Perú según el estado de VIH autoreportado (PVVIH, negativo, desconocido) durante 2021 utilizando una encuesta en línea. Se estimaron dos modelos mediante regresión de Poisson para cada grupo: Modelo A, que incluyó factores sociodemográficos (país, sexo, edad, raza, educación e ingresos) y Modelo B, que incluyó recibir TAR (para PVVIH) o comportamiento de riesgo, uso de PrEP y percepción de riesgo (para VIH negativo o desconocido). Se incluyó 21,590 encuestados (Brasil: 61%, México: 30%, Perú: 9%). Entre aquellos negativos para VIH (74%) y con estado desconocido (12%), el 13% utilizó alguna vez PrEP. Entre las PVVIH (13%), el 93% reportó recibir actualmente TAR. La concienciación de I = I fue del 89% tanto en Brasil como en México, superior al 64% de Perú. La concienciación de I = I fue mayor entre PVVIH (96%) que entre los VIH-negativos (88%) y los VIH-desconocidos (70%). En los modelos multivariados, las PVVIH con menor educación eran menos conscientes de I = I, mientras que los que tomaban TAR eran más conscientes. Entre los VIH-negativos, las personas no cisgéneros, con menores ingresos y con menor educación eran menos consciente de I = I, mientras que los que tenían experiencia usando PrEP eran más conscientes. En conclusión, la concienciación sobre I = I varió según el estado serológico de VIH, las características sociodemográficas y el comportamiento de riesgo. El concepto de I = I debe difundirse a través de estrategias educativas, incluyendo un enfoque en MSG para combatir el estigma del VIH.
Subject(s)
HIV Infections , Health Knowledge, Attitudes, Practice , Self Report , Sexual and Gender Minorities , Humans , Male , Female , HIV Infections/drug therapy , HIV Infections/psychology , HIV Infections/epidemiology , Adult , Brazil/epidemiology , Peru/epidemiology , Sexual and Gender Minorities/psychology , Sexual and Gender Minorities/statistics & numerical data , Middle Aged , Mexico/epidemiology , Young Adult , Adolescent , Sexual Behavior/psychology , Risk-Taking , Surveys and Questionnaires , Sexual Partners , Pre-Exposure Prophylaxis/statistics & numerical dataABSTRACT
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a significant global health problem. In immunocompetent individuals, the microorganism can remain in a latent, non-contagious form, however, it may become active under conditions of immunosuppression. Tumour necrosis factor (TNF) inhibitors, which are frequently used for the management of immune-mediated disorders like psoriasis, have been associated with a significantly increased risk of reactivating latent TB. Consequently, international guidelines recommend TB screening and preventive treatment before starting anti-TNF therapy. These recommendations have extended to IL-12/23, IL-17, IL-23 and TYK2 inhibitors under a caution principle, despite their different mechanisms of action. However, current evidence suggests that some of these agents are arguably not associated with an increased risk of TB reactivation or development of TB disease after infection, which calls for a critical reassessment of these guidelines. We have conducted a literature search evaluating the risk of TB reactivation associated with these innovative therapies, integrating findings from both randomized clinical trials and real-world evidence. The identified evidence is limited but the low number of identified cases of reactivation with IL-17 and IL-23 inhibitors prompts reconsidering the need for preventive treatment for latent TB in all cases, regardless of biologic class or individual patient's risk of TB reactivation or drug toxicity. This review, along with the clinical insight of a panel of experts on behalf of the SPIN-FRT, led to the development of these consensus recommendations for managing psoriasis treatment in patients with latent TB infection or at risk of TB infection, who are receiving or are intended to receive biologic and non-biologic targeted therapies. These recommendations highlight the need for updates to the existing guidelines, aiming to provide a more differentiated approach that reflects the evolving landscape of psoriasis treatment and its implications for TB management.
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BACKGROUND: Dermatological research has traditionally concentrated on evaluating mental comorbidities, neglecting positive concepts like happiness. Initial studies indicate that psoriasis and atopic dermatitis (AD) impair the happiness of those affected. Considering global happiness variations, this study aimed to explore the disease- and country-specific differences in disease-related quality of life and happiness, and potential influential factors on heuristic happiness among psoriasis and AD patients in Europe. METHODS: A cross-sectional multicentre study was conducted in dermatology departments of university-affiliated hospitals in eight European countries (Austria, Germany, Italy, Malta, Poland, Portugal, Romania and Ukraine) between October 2021 and February 2023. Adult psoriasis and AD patients completed a standardized questionnaire in their native languages, providing data on demographics, disease-related characteristics, disease-related quality of life (Dermatology Life Quality Index, DLQI), heuristic happiness, positive affect (PA), negative affect (NA) and satisfaction with life (SWL). Descriptive analysis and quantile regression were performed. RESULTS: Between psoriasis (n = 723) and AD (n = 316) patients almost no differences were observed in happiness, SWL and NA, except for DLQI and small differences in PA, with AD patients reporting greater impact than psoriasis patients. Country-wise variation emerged in DLQI, heuristic happiness, PA, NA and SWL with Austrian patients displaying the highest levels of happiness, satisfaction and positivity, coupled with higher treatment care and lower disease severity. Quantile regression revealed varying coefficients for predictor variables across quantiles, indicating, for example positive effects on heuristic happiness associated with current or previous receipt of systemic therapies at different quantiles. CONCLUSION: This study shows notable happiness differences across European countries and significant disease-related variations, particularly with AD patients being more impaired than psoriasis patients. The findings highlight the need for equality in treatment access and support the development of targeted positive psychological interventions to enhance happiness considering country-specific distinctions in future research and health policies for psoriasis and AD patients.
ABSTRACT
OBJECTIVES: Although catastrophic health spending is the main measure for assessing financial healthcare protection, it varies considerably in methodological and empirical terms, which hinders comparison between studies. The aim of this study was to measure the prevalence of catastrophic health spending in Brazil in 2003, 2009, and 2018, its associated factors, and disparities in prevalence distribution according to socioeconomic status. STUDY DESIGN: This was a time series study. METHODS: Data from the Household Budget Surveys were used. Prevalence of catastrophic health spending was measured as a percentage of the budget and ability to pay, considering thresholds of 10, 25, and 40%. It was determined whether household, family, and household head characteristics influence the likelihood of incurring catastrophic health spending. Households were stratified by income deciles, consumption, and wealth score. RESULTS: There was an increase in prevalence of catastrophic health spending between 2003 and 2009 in Brazil and a slight reduction in 2018. The wealth score showed more pronounced distributional effects between the poor and the rich, with the former being the most affected by catastrophic health spending. Consumption showed greater percentage variations in the prevalence of catastrophic health spending. The prevalence of catastrophic health spending was positively associated with the presence of older adults, age and female household head, rural area, receipt of government benefits, and some degree of food insecurity. CONCLUSIONS: The poorest families are most affected by catastrophic health spending in Brazil, requiring more effective and equitable policies to mitigate financial risk.
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BACKGROUND: Rapid skin improvement is a key treatment goal of patients with moderate-to-severe psoriasis (PsO). OBJECTIVES: To compare the speed of clinical improvement of approved biologics on the symptoms and signs of psoriasis assessed by patients using the validated Psoriasis Symptoms and Signs Diary (PSSD) through 12 weeks. METHODS: Psoriasis Study of Health Outcomes (PSoHO) is an international, prospective, non-interventional study that compares the effectiveness of anti-interleukin (IL)-17A biologics versus other biologics, together with pairwise comparisons of ixekizumab versus five individual biologics in patients with PsO. Using the PSSD 7-day recall period, patients assessed the symptoms (itch, skin tightness, burning, stinging and pain) and signs (dryness, cracking, scaling, shedding/flaking, redness and bleeding) of their psoriasis (0-10). Symptom and sign summary scores (0-100) are derived from the average of individual scores. Percentage change in summary scores and proportion of patients with clinically meaningful improvements (CMI) in PSSD summary and individual scores are evaluated weekly. Longitudinal PSSD data are reported as observed with treatment comparisons analysed using mixed model for repeated measures (MMRM) and generalized linear mixed models (GLMM). RESULTS: Across cohorts and treatments, eligible patients (n = 1654) had comparable baseline PSSD scores. From Week 1, the anti-IL-17A cohort achieved significantly larger score improvements in PSSD summary scores and a higher proportion of patients showed CMIs compared to the other biologics cohort through 12 weeks. Lower PSSD scores were associated with a greater proportion of patients reporting their psoriasis as no longer impacting their quality-of-life (DLQI 0,1) and a high level of clinical response (PASI100). Results also indicate a relationship between an early CMI in PSSD score at Week 2 and PASI100 score at Week 12. CONCLUSIONS: Treatment with anti-IL-17A biologics, particularly ixekizumab, resulted in rapid and sustained patient-reported improvements in psoriasis symptoms and signs compared with other biologics in a real-world setting.
Subject(s)
Biological Products , Psoriasis , Humans , Antibodies, Monoclonal/therapeutic use , Prospective Studies , Severity of Illness Index , Psoriasis/complications , Psoriasis/drug therapy , Psoriasis/diagnosis , Patient Reported Outcome Measures , Biological Products/therapeutic use , Pain/drug therapy , Treatment OutcomeABSTRACT
BACKGROUND: Randomized controlled trials of secukinumab have shown sustained efficacy and a favourable safety profile in multiple manifestations of psoriatic disease. OBJECTIVES: To assess the long-term, real-world retention, effectiveness and safety of secukinumab in routine clinical practice for the treatment of moderate-to-severe plaque-type psoriasis (PsO). METHODS: SERENA (CAIN457A3403) is a large, ongoing, longitudinal, observational study conducted at 438 sites and 19 countries for an expected duration of up to 5 years in adult patients with moderate-to-severe PsO, psoriatic arthritis and ankylosing spondylitis. Patients received ≥16 weeks of secukinumab treatment before enrolment. This interim analysis presents data from PsO patients, who were enrolled in the study between October-2016 and October-2018 and were observed for ≥2 years. RESULTS: In total, 1756 patients (67.3% male) with a mean age of 48.4 years and body mass index of 28.8 kg/m2 were included in the analysis. The secukinumab treatment retention rates after 1, 2 and 3 years in the study were 88.0%, 76.4% and 60.5%, respectively. Of the 648 patients who discontinued the study, the most common reasons included lack of efficacy (42.6%), adverse event (17.4%), physician decision (12.2%) and subject decision (11.6%). Mean ± SD absolute PASI was 21.0 ± 13.0 at the start of treatment (n = 1,564). At baseline, the mean ± SD PASI score reduced to 2.6 ± 4.8 and remained low at Year 1 (2.3 ± 4.3), Year 2 (1.9 ± 3.6) and Year 3 (1.9 ± 3.5). The safety profile of secukinumab during the SERENA study was consistent with its known safety profile, with no new safety signals reported. Particularly, low rates of inflammatory bowel disease (0.3%; Incidence Rate [IR]:0.15), candida infections (3.1%; IR:1.43) and MACE (0.9%; IR:0.37) were observed. CONCLUSIONS: Secukinumab showed high treatment persistence, sustained effectiveness and a favourable safety profile up to 3 years of follow-up in the real-world population of PsO patients observed in SERENA.
Subject(s)
Antibodies, Monoclonal , Psoriasis , Adult , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Female , Humans , Male , Middle Aged , Psoriasis/chemically induced , Psoriasis/drug therapy , Severity of Illness Index , Treatment OutcomeABSTRACT
BACKGROUND: The COVID-19 pandemic has raised questions regarding the management of chronic skin diseases, especially in patients on systemic treatments. Data concerning the use of biologics in adults with psoriasis are reassuring, but data specific to children are missing. Moreover, COVID-19 could impact the course of psoriasis in children. OBJECTIVES: The aim of this study was therefore to assess the impact of COVID-19 on the psoriasis of children, and the severity of the infection in relation to systemic treatments. METHODS: We set up an international registry of paediatric psoriasis patients. Children were included if they were under 18 years of age, had a history of psoriasis, or developed it within 1 month of COVID-19 and had COVID-19 with or without symptoms. RESULTS: One hundred and twenty episodes of COVID-19 in 117 children (mean age: 12.4 years) were reported. The main clinical form of psoriasis was plaque type (69.4%). Most children were without systemic treatment (54.2%); 33 (28.3%) were on biologic therapies, and 24 (20%) on non-biologic systemic drugs. COVID-19 was confirmed in 106 children (88.3%) and 3 children had two COVID-19 infections each. COVID-19 was symptomatic for 75 children (62.5%) with a mean duration of 6.5 days, significantly longer for children on non-biologic systemic treatments (P = 0.02) and without systemic treatment (P = 0.006) when compared with children on biologics. The six children who required hospitalization were more frequently under non-biologic systemic treatment when compared with the other children (P = 0.01), and particularly under methotrexate (P = 0.03). After COVID-19, the psoriasis worsened in 17 cases (15.2%). Nine children (8%) developed a psoriasis in the month following COVID-19, mainly a guttate form (P = 0.01). DISCUSSION: Biologics appear to be safe with no increased risk of severe form of COVID-19 in children with psoriasis. COVID-19 was responsible for the development of psoriasis or the worsening of a known psoriasis for some children.
Subject(s)
Biological Products , COVID-19 , Psoriasis , Adolescent , Adult , Biological Factors/therapeutic use , Biological Products/therapeutic use , COVID-19/complications , Child , Disease Progression , Humans , Methotrexate/therapeutic use , Pandemics , Psoriasis/complications , Psoriasis/drug therapy , Psoriasis/epidemiology , RegistriesABSTRACT
BACKGROUND: Using sulfated polysaccharides (SP) in fish sperm freezing medium promotes cell maintenance. OBJECTIVE: To evaluate the effect of different SP concentrations, extracted from two seaweeds (Gracilaria domingensis and Ulva fasciata), as a supplement to the sperm freezing medium of Prochilodus brevis. MATERIALS AND METHODS: Five semen pools were diluted in a solution composed of 5% glucose, 10 % dimethyl sulfoxide (DMSO) and different SP concentrations (0, 0.5, 1.0, 1.5, 2.0, 2.5 or 3.0 mg/mL). The samples were cryopreserved and, after 7 days, rewarmed and analyzed for morphology, plasma membrane integrity, DNA integrity, mitochondrial activity and sperm kinetics [total motility, progressive motility, curvilinear velocity (VCL), straight line velocity (VSL), average path velocity (VAP), linearity (LIN), and wobble (WOB)]. RESULTS: There was no interaction between seaweed and SP concentrations. Similar effects were observed with SP extracted from the two seaweeds, regardless of concentration. When comparing the SP concentrations, regardless of the seaweed, 1.0 mg/mL SP showed better results for VCL and VSL. For VAP and WOB, 1.0 mg/mL SP showed better results, but differed from 3.0 mg/mL. LIN followed the same pattern, but differed from SP at 2.5 and 3.0 mg/mL. For progressive motility, 1.0 mg/mL G. domingensis showed superior results compared to the control. For mitochondrial activity, G. domingensis was superior to U. fasciata, regardless of concentration. The lowest concentrations (0.5 and 1.0 mg/mL) showed the best results, regardless of the seaweed. However, the control was superior to all treatments tested. CONCLUSION: G. domingensis SP at the lowest concentrations might be a potential supplement to the P. brevis freezing medium. doi.org/10.54680/fr22210110412.
Subject(s)
Characiformes , Fertility Preservation , Semen Preservation , Animals , Male , Freezing , Cryopreservation/methods , Sulfates , Sperm Motility , Semen Preservation/veterinary , Semen Preservation/methods , Spermatozoa , GlucoseABSTRACT
BACKGROUND: Registry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID-19) outcomes compared with patients receiving no systemic treatments. OBJECTIVES: We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation. METHODS: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk-mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed-effects model. RESULTS: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk-mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35-1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23-1·56). Shielding was associated with established risk factors for severe COVID-19 [male sex (OR 1·14, 95% CI 1·05-1·24), obesity (OR 1·37, 95% CI 1·23-1·54), comorbidity burden (OR 1·43, 95% CI 1·15-1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27-1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36-1·80). Modest differences in the proportion shielding were observed across nations. CONCLUSIONS: Greater risk-mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID-19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence-based patient communication on risk-mitigation strategies and may help inform updated public health guidelines as the pandemic continues.
Subject(s)
COVID-19 , Joint Diseases , Cross-Sectional Studies , Humans , Male , Pandemics , SARS-CoV-2ABSTRACT
Tuberculosis is an infectious disease with a major global impact, ranked in the top 10 mortality causes worldwide. In an immunocompetent individual, the host defence mechanisms control Mycobacterium tuberculosis infection and induce the latent form of the disease. However, in the presence of diseases or therapies, which exert an immunosuppressive effect, latent tuberculosis can be re-activated. Psoriasis is an immune-mediated, inflammatory disease, and its treatment has rapidly evolved over the last few years. It has long been recognized that the tumour necrosis factor (TNF)-α inhibitors are associated with increased risk of reactivation of latent tuberculosis infection. Thus, international guidelines have been suggesting tuberculosis screening before starting the treatment with all biological agents since then. In addition, the institution of chemoprophylaxis in the presence of latent tuberculosis and the annual screening for tuberculosis thereafter have also been indicated. However, anti-tuberculosis treatments can have significant side-effects and there are currently several contraindications to their use. The risk benefit of starting anti-tuberculous treatment should be carefully weighed up. The emergence of new biological drugs for the treatment of psoriasis, such as interleukin (IL)-17 and IL-23 inhibitors, has reignited the subject of tuberculosis reactivation as it is possible that IL-17 and 23 blockade do not carry the same risk of TB reactivation as TNF-α inhibitors. Although preclinical studies have shown that cytokines IL-17 and IL-23 have a possible role against infection with M. tuberculosis, data from clinical trials and post-marketing surveillance with drugs that inhibit these cytokines appear to suggest that they are not crucial to this response. In this article, we review the available data on tuberculosis reactivation after the treatment of psoriasis with IL-17 and IL-23 inhibitors, and its possible impact on the way we currently manage latent tuberculosis infection before or after starting treatment with these new drugs.
Subject(s)
Latent Tuberculosis , Mycobacterium tuberculosis , Psoriasis , Tuberculosis , Humans , Interleukin-17 , Interleukin-23 , Latent Tuberculosis/chemically induced , Psoriasis/drug therapy , Tumor Necrosis Factor-alphaABSTRACT
BACKGROUND: Sulfated polysaccharides from the skin of Nile tilapia (Oreochromis niloticus), added to the tambaqui (Colossoma macropomum) semen diluting medium, can be potential antioxidants and promote the maintenance of sperm quality. OBJECTIVE: To evaluate the use of different concentrations of glycosaminoglycans (GAGs) from the skin of Nile tilapia as a supplement in two cryogenic media for tambaqui semen. MATERIALS AND METHODS: Tambaqui males received a single dose of pituitary carp extract. The semen was collected for pool analysis and, later, cryopreserved in liquid nitrogen. The pools were diluted and frozen in a solution containing fish-specific powdered coconut water (ACP-104) and 10% DMSO or 5% Glucose and 10% DMSO and supplemented with different concentrations of GAGs. The controls had no GAGs addition. After 45 days, the samples were thawed by immersion in a water bath and evaluated for membrane and DNA integrity, morphology and sperm kinetics. RESULTS: The parameters of linearity (LIN), straightness (STR) and DNA integrity of sperm frozen in 5% Glucose showed better results than ACP-104. For membrane integrity, concentrations of 0 and 1.0 mg/mL were better than 5 mg/mL. Semen motility in 5% Glucose showed superior results at concentrations lower than 5 mg/mL of GAGs. For VCL and VAP, in ACP-104, 3.0 mg/mL exceeded the other treatments. In 5% Glucose, for VCL, 4.0 mg/mL showed the lowest results compared to concentrations of <3.5 mg/mL and, for VAP, it also differed from 4.5 mg/mL CONCLUSION: Therefore, the skin of Nile tilapia has GAGs, in low concentrations, capable of improving the post-thawed sperm quality of tambaqui, especially in 5% Glucose medium.
Subject(s)
Fertility Preservation , Semen Preservation , Tilapia , Animals , Cryopreservation/methods , Cryopreservation/veterinary , Cryoprotective Agents/pharmacology , Glycosaminoglycans/pharmacology , Male , Semen Preservation/methods , Semen Preservation/veterinary , SpermatozoaABSTRACT
BACKGROUND: A long-term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. OBJECTIVES: To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate-to-severe atopic eczema, to assess the long-term safety risk of these therapies in a routine clinical care setting. METHODS: We describe a registry-embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. CONCLUSIONS: This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long-term data on the safety of systemic immunomodulating therapies in patients with atopic eczema. Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long-term safety profile against established therapies. Large numbers of patients with a long duration of follow-up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries. We present a protocol for an investigator-initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate-to-severe atopic eczema. This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations.
Subject(s)
Dermatitis, Atopic , Eczema , Adolescent , Adult , Antibodies, Monoclonal, Humanized , Child , Dermatitis, Atopic/drug therapy , Humans , Observational Studies as Topic , Prospective Studies , Registries , Treatment OutcomeABSTRACT
In this work, we studied structural and magnetic properties of 18 nm sized Zn-substituted magnetite, 28 nm sized unsubstituted and 17 nm sized (Mn, Zn)-substituted iron oxide nanoparticles, synthesized by thermal decomposition method. Their features were examined by analyzing the x-ray diffraction data, 57Fe Mössbauer spectra and magnetization measurements by SQUID interferometer. The microstructure was inspected comparing the different size and strain broadening models incorporated into Fullprof software. In terms of crystallinity and size dispersion, applied synthesis protocol shows superiority over decomposition of iron oleate and the co-precipitation synthesis route. The saturation magnetization at T = 5 K was found to be within the M S = 91.2-98.6 A m2 kg-1 range, while at 300 K M S of pure and Zn-substituted Fe3O4 nanoparticles is 83.6 and 86.2 A m2 kg-1, respectively. Effective magnetic anisotropy constant K eff, estimated under slow measurements by SQUID, is below 20 kJ m-3 in all three samples. Some preliminary measurements of the magnetic hyperthermia performance, expressed via specific absorption rate value showed that the best heating performances were displayed by 18 nm sized oleic acid-coated Zn0.13Fe2.87O4 cubo-octahedrons with SAR â 425 W/gFe at H 0 = 20 kA m-1 and f = 228 kHz.
ABSTRACT
Aqueous two-phase systems have been studied for almost a century to separate biomolecules in harmless conditions. Proteases produced by Aspergillus tamarii URM 4634 were extracted in polyethylene glycol (PEG)/phosphate aqueous two-phase system under discontinuous and continuous (perforated rotative discs column) process. On the discontinuous process, it was evaluated the effect of operational conditions (PEG molar mass and its concentration, phosphate concentration and pH) over the partition coefficient, activity yield and purification factor. Protease partitioned to PEG-phase with partition coefficients up to 55.73. The best process parameters were 17.5% of PEG, with molar mass 8000 g·mol-1, 15% of phosphate salt at pH 6, with 113.15% of activity yield and purification factor of 2.62. Under continuous extraction, hold up data showed that 57.1% of the discontinuous phase was available for protein extraction. Further, separation achieved 90.0% of efficiency. The yields surpassed 100% in almost all runs, and the best purification factor was 1.84, with both flows of 2 mL·min-1. Thus, the best operational conditions reached an activity yield of 95.3% and 90.0% of separation efficiency. Hence, aqueous two-phase system PEG/phosphate extraction is an efficient process for separation of proteases produced by Aspergillus tamarii URM 4634, under continuous extraction likewise under discontinuous process.
Subject(s)
Aspergillus/enzymology , Fungal Proteins/isolation & purification , Liquid-Liquid Extraction/methods , Peptide Hydrolases/isolation & purification , Fermentation , Hydrogen-Ion Concentration , Molecular Weight , Phosphates/chemistry , Polyethylene Glycols/chemistry , Water/chemistryABSTRACT
Different types of topical preparations are available as anti-psoriatic medicines, semisolid formulations being the preferred dosage forms for the treatment of body lesions. The mechanical characterization of these semisolid formulations is seldom reported, although mechanical features have been recognized to play an important role in treatment acceptability and adherence. The aim of this study was to characterize the mechanical properties of semisolid topical formulations commercially available for psoriasis treatment. One complementary aim was to evaluate patient satisfaction with topical treatment and discuss the results according to the mechanical features of the dosage form. Eight ointments (O 1-8), five creams (C 1-5), one oleogel (G1), and one excipient (E1-petrolatum) were characterized for textural properties (spreadability and penetration tests) and flow behavior. Power law model was fitted to the results. A questionnaire for the assessment of satisfaction with topical medicines used for psoriasis treatment over 6 months was developed and applied to 79 psoriasis patients. All the tested formulations presented a shear-thinning behavior with power law indexes (n) lower than 1. Ointments were distinct from the other dosage forms, since they presented higher consistency coefficients (K), firmness, and adhesiveness and this was evidenced by hierarchical cluster analysis, which identified two clusters based on the mechanical properties. Cluster 1 included the ointments and petrolatum and the cluster 2 enclosed the creams and the gel. The clusters were associated with several attributes classified by patients as analyzed with Fisher's exact test. In all cases, higher satisfaction was observed for cluster 2. The knowledge obtained regarding the influence of the dosage form on the degree of satisfaction with the treatment could be helpful in supporting the selection of the dosage form in clinical practice and thus improve treatment adherence and clinical outcomes. The differences observed between the mechanical properties of the formulations studied may be also relevant to the industry, as guidance to the development of new medicines.