Influence of Clinical and Psychosocial Factors on the Adherence to Topical Treatment in Psoriasis.

(1) Background: Psoriasis is a common chronic inflammatory skin disease with different manifestations, affecting the quality of life at social, emotional, and professional dimensions and requiring long-term treatment. This study aimed to investigate the effect of psychosocial and clinical factors on adherence to topical treatment in psoriasis. (2) Methods: Self-reported measures and weighing the medicines were used to assess adherence. Psychopathological symptoms were measured using the Brief Symptoms Inventory (BSI). Social and clinical factors were assessed by a sociodemographic and clinical questionnaire. Adherence to treatment with topical medication was assessed using a sample of 102 psoriasis patients. (3) Results: The explanatory models of adherence to topical treatment in psoriasis translated into positive associations between adherence and the education level (higher education) (p = 0.03; φ = 0.23), the single-family household (p = 0.01; φ = 0.44), active employment status (p = 0.05; φ = -0.19), familiar history of psoriasis (p = 0.04; φ = -0.21), and the presence of obsessive-compulsive symptoms (p = 0.01; d = 0.29). (4) Conclusions: In patients who present the characteristics identified that influence non-adherence, instructions should be reinforced to increase adherence. The experimental mortality (39.6%) reduced the sample size, representing a limitation of the study.

Dermatological Side Effects of Cancer Treatment: Psychosocial Implications-A Systematic Review of the Literature.

Cancer is a leading cause of mortality and morbidity all over the world and the second major cause of death in Portugal. Dermatological side effects resulting from cancer treatment have a psychosocial impact on patients' lives, such as quality of life (QoL), body image, cognitive fusion and social inhibition. This systematic review aimed to explore and synthesize the psychosocial impact of dermatological side effects of cancer treatment, answering the following research objectives: (i) Do the dermatological side effects of the cancer treatment present any psychosocial impact for the patients? (ii) How does the psychosocial impact of the dermatological toxicities of the cancer treatment manifest in patients' lives? Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed and guided a systematic search through the PubMed, Cochrane Library and PyscNet databases. The considered studies correlate dermatological side effects of cancer treatments and their psychological/psychosocial outcomes. The studies found were all published in peer-reviewed journals. The results obtained established that cancer treatment causes the most varied skin changes, consequently reducing self-esteem and QoL; disturbing body image; and contributing to cases of stress, depression and anxiety. There is still limited literature that profoundly investigates the experience of living with these skin toxicities. The development of research lines to improve knowledge in this field will allow for significant improvements in healthcare for patients undergoing cancer treatment who need to focus more on the psychosocial implications of skin toxicities. The novelty of this review lies in adding knowledge summarizing the psychosocial implications of dermatological side effects of cancer treatment to support healthcare providers in the development of integrative therapeutic strategies for these patients in their clinical practice.

Influence of psoriasis lesions' location and severity on psychosocial disability and psychopathology. Observational study and psychometric validation of the SAPASI Portuguese version.

OBJECTIVES: The psychosocial impact of psoriasis is well documented. However, the contributing role of clinical disease characteristics is not satisfactorily explored. This study aimed to validate the Self-administered Psoriasis Area and Severity Index (SAPASI) to a Portuguese population (SAPASI-PT) and to perform its cross-validation, assessing how the results will generalize to an independent data set, with the Psoriasis Area and Severity Index (PASI), in order to assess the influence of psoriasis' severity on psychosocial disability and psychopathology. METHODS: A cross-sectional study with 228 patients with psoriasis was carried out. Data was collected through a sociodemographic and clinical questionnaire, SAPASI-PT, the Psoriasis Disability Index (PDI) and the Brief Symptoms Inventory (BSI). The cultural and linguistic adaptation of SAPASI to a Portuguese version and the cross validation with PASI was carried out. Multiple associations between psychosocial disability, psychopathology and severity, discomfort and location of lesions were investigated through logistic regression models. RESULTS: A good adjustment model for SAPASI-PT is found. Also, associations between psychosocial disability, psychopathology and the psoriasis severity and discomfort are found. The existence of lesions is positively associated with the severity of the disease. Patients with lesions in hands or genitals are those reporting a greater discomfort. The presence of lesions in hands is positively associated with PDI, i.e., with leisure and with treatment, marginally. Additionally, patients scoring higher in the personal dimension are found to have a significantly greater percentage of lesions in the genitals. CONCLUSIONS: The psoriasis severity and location of lesions are important determinants of patients´ quality of life. Lesions on face, hands and genitals are associated with a higher impact on psychosocial wellbeing of patients. Psychological counselling should be considered within psoriasis treatment context in patients with the described disease manifestations.

Patterns of dosage regimen instructions regarding topical medicines: how is the information perceived by patients?

BACKGROUND: The communication of dosage regimen instructions by physicians is of utmost importance on treatment adherence. Few studies until now have approached the topical treatment adherence subject. OBJECTIVE: This study aims the characterization of dosage regimen instructions given by physicians and the assessment of chronic dermatological patients' perception regarding these instructions. METHODS: Two instruments one for physicians (PHYSDOSAGE) and one for patients (PATIENTDOSAGE) were developed and applied in a cross-sectional, descriptive and exploratory study to two independent samples composed by 91 physicians and 43 patients. RESULTS: Most of physicians reported to provide dosage regimen instructions. When cross checking information from both studied samples, physicians and patients, it was concluded that physicians reported to provide more frequently oral and written treatment instructions, e.g. electronic prescription, than patients reported having received it. Also, physicians claimed to often provide information about the duration of treatment and the frequency of topical medicines' application, which was not acknowledged by patients. CONCLUSIONS: Contradictory results were found between the physicians' information input and the patients' perception about dosage regimen instructions provided during the consultation. These findings could negatively influence the treatment adherence and the clinical outcomes. Thus, it is of paramount importance the implementation of strategies to improve optimal communication of dosage regimen instructions for topical medicines.

Does the Vehicle Matter? Real-World Evidence on Adherence to Topical Treatment in Psoriasis.

The influence of the vehicle in topical treatment adherence remains to be elucidated. The aim of this study is to analyze the influence of the pharmaceutical dosage form on adherence to topical treatment in psoriasis patients, taking into consideration the mechanical features. The adherence was evaluated in a sample of 102 psoriasis patients, followed for approximately 45 days. Adherence was calculated with a new combined methodology using a log and medication weights. The effect of the group formulation was evaluated using logistic regression models. A complex effect of the vehicle on adherence was found, mediated by the affected area. The adherence was significantly higher for patients applying gels and creams than for those using ointments, whenever the body area affected was extensive. The opposite was found when the affected area was small. Mechanical properties can partially explain the findings since gels and creams may be easier to apply. Patient beliefs and preferences regarding vehicles and their sensory attributes might also explain the results. It is noteworthy that adherence was strikingly low, with more than 75% non-adherent patients. This real-world evidence provides an insight for pharmaceutical industries and guidance for treatment prescription by physicians aiming to address the public health emergency of treatment non-adherence.

Knowledge and Practices of Community Pharmacists in Topical Dermatological Treatments.

The connection between pharmacists' knowledge and practice on the provided information to patients about dermatoses and their treatment is insufficiently characterized. Furthermore, pharmacists' contributions in counselling and in promoting adherence to topical treatment is not fully understood. This study has three main objectives. It aims to identify the knowledge and practices of pharmacists about dermatoses and their treatment, and to compare the perspective of pharmacists with that of patients regarding treatment information, with the future goal of establishing guidelines on the communication of dosage regimen instructions to dermatological patients and promotion of adherence to treatment, filling a gap. A cross-sectional, exploratory, and descriptive study was carried out. Based on experts' prior knowledge and extensive collected literature information, two questionnaire protocols, one for pharmacists and another one for patients, were designed. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were carried out in relation to the pharmacists' questionnaire for instrument validation. The results indicate that knowledge of pharmacists regarding dermatoses and their treatment is considered acceptable. Most of the pharmacists were reported to provide information to patients. Oppositely, patients reported not to have receive it. This is an important issue because pharmacists play a primary role in the management of several diseases. As non-adherence can be triggered by poor understanding of the dosing instructions, pharmacists' communication practices play an important role in improving this hinderance. Results from this study identified pharmacist-patient communication gaps, so the development of guidelines to improve the transmission of clear dosage regimen instructions and knowledge about patient's disease are of paramount importance. Training programs for continuous education of pharmacist should be implemented to solve the identified communication problems found in this study.

The Mediator Role of Body Image-Related Cognitive Fusion in the Relationship between Disease Severity Perception, Acceptance and Psoriasis Disability.

Psoriasis is a long-term skin disorder without a cure, whose patients are particularly susceptible to mental health diseases. Using a sample of patients diagnosed with psoriasis, this study aimed to: (1) identify the clinical and positive psychological variables that contribute the most to psoriasis disability and (2) assess the mediator role of body image-related cognitive fusion in the relation between disease severity perception and acceptance and self-compassion, on one hand, and psoriasis disability on the other. This is an initial cross-sectional exploratory study, with 75 patients diagnosed with psoriasis (males 52%; mean age 54.99 ± 13.72) answering a sociodemographic and a clinical questionnaire, the Psoriasis Disability Index (PDI), the Cognitive Fusion Questionnaire-Body Image (CFQ-BI), the Acceptance and Action Questionnaire-II (AAQ-II), and the Self-Compassion Scale (SCS). Descriptive and inferential statistics were used to characterize and assess the measures and the final model used. Through path analysis and a hierarchical multiple linear regression, it was found that the variables that significantly contributed to psoriasis disability were years of education, impact on social life and body image, explaining 70% of the variance. Body image-related cognitive fusion was a significant mediator in the relationship between disease severity and acceptance, and psoriasis disability. The implications of this study are considered to be extremely relevant, since it will allow additional information to be provided to psoriasis patients, appropriated to their educational level, aiming to reduce distorted perceptions of disease severity and intervene in the ability to accept this specific and important chronic health condition.

Development and characterization of PLGA nanoparticles containing 1,3-dihydroxy-2-methylxanthone with improved antitumor activity on a human breast cancer cell line.

Interest on xanthones has been growing considerably due to their broad spectrum of biological activities. 1,3-Dihydroxy-2-methylxanthone (DHMXAN) showed a significant inhibitory effect on the growth of MCF-7 cancer cells. DHMXAN-loaded nanosphere and nanocapsule formulations were prepared by the solvent displacement technique with the aim of improving the delivery of this poorly water-soluble compound. Moreover, we investigated the usefulness of this nanotechnology-based approach on the improvement of compound's antitumor activity. Nanosphere and nanocapsule mean diameters ranged from 117 ± 8 to 138 ± 5 nm and from 266 ± 7 to 286 ± 22 nm, respectively, and both systems exhibited negative surface charge. Incorporation efficiency values of DHMXAN in nanospheres and nanocapsules were higher than 30% (30.9 ± 3.3 to 38.8 ± 3.6%) and 80% (85 ± 7 to 88 ± 6%), respectively. The release study of DHMXAN from nanocapsules suggests that drug release is mainly governed by its partition between the oil core and the external aqueous medium. The effect of different nanoparticulate formulations on the growth of human breast cancer cell line MCF-7 was evaluated using the sulforhodamine B (SRB) assay. Incorporation of DHMXAN in nanospheres and nanocapsules afforded a marked potentiation of the compound inhibitory effect.

Qualidade do sono das crianças e adolescentes internados em unidades pediátricas / Sleep quality in children and adolescents hospitalized in pediatric units

Enquadramento: A qualidade do sono é essencial para o bem-estar do indivíduo e influenciador na recuperação e funcionamento do organismo. Ao nível hospitalar, um conjunto de fatores físicos, psicológicos e ambientais poderá interferir na qualidade de sono em crianças internadas. Objetivos: Com esta investigação pretendeu-se analisar a qualidade de sono das crianças e adolescentes com, pelo menos, três dias completos de internamento em unidades pediátricas; comparar a qualidade de sono dessas crianças e adolescentes um mês antes do internamento e caracterizar a relação de algumas variáveis sociodemográficas e clínicas na qualidade de sono em ambiente hospitalar. Metodologia: É um estudo quantitativo, descritivo-correlacional onde participaram 58 crianças/adolescentes com idades compreendidas entre os 8 e os 18 anos internados em unidades pediátricas, sendo a amostra não probabilística consecutiva. O instrumento de colheita de dados foi constituído por um questionário de caracterização sociodemográfica e clínica, o índice da qualidade de sono de Pittsburgh e uma adaptação desse instrumento ao internamento. Resultados: Cerca de um terço das crianças e adolescentes apresentam má qualidade de sono no domicílio, sendo que, durante o internamento, este número aumenta para 63,8%, no entanto, a sua perceção sobre a qualidade do sono é boa ou muito boa (70,7%). A média de horas de sono por noite é de 7:35 horas, estando abaixo do valor recomendado para esta faixa etária. A maioria (98,2%) refere ter perturbações do sono no internamento. Este estudo confirmou a existência de relação entre qualidade de sono no internamento e as variáveis sexo e escolaridade. Todavia, em relação às variáveis clínicas, não se verificou associação estatisticamente significativa. Conclusão: As crianças e adolescentes internados em unidades pediátricas apresentam maior prevalência de sono de má qualidade, comparando com uma situação de não internamento. Estes resultados têm implicações clínicas prováveis, pelo que as instituições e profissionais de saúde devem identificar práticas e rotinas que favoreçam a qualidade do sono e, consequentemente, o bem-estar e a recuperação.

Development and Validation of a Novel Questionnaire for Adherence with Topical Treatments in Psoriasis (QATOP).

BACKGROUND: Self-report measures are the most used methodologies for the evaluation of adherence to psoriasis topical treatment, although currently there is no standard questionnaire for this purpose. OBJECTIVE: The present study aimed at developing a novel questionnaire (Questionnaire for Adherence to TOPical treatment [QATOP]) for the assessment of adherence to topical treatment in psoriasis. METHODS: A questionnaire containing nine items organized into two parts (part 1: current patient treatment; part 2: adherence to treatment, amount used, and treatment-associated variables) was developed, supported by a systematic literature review, qualitative patient focus interviews, and expert-group input. Its content validity was determined by a pilot study of six patients. Adherence to topical treatment was then assessed in 35 patients with psoriasis, after 45 days of treatment, using the QATOP and a medication log. Associations between different items of the QATOP and the log were investigated. RESULTS: Adherence results were 63.5 ± 29.2% for the log and 60.9 ± 24.4% for the QATOP, and were strongly correlated (R = 0.819, p < 0.001). Distinct posologic regimens were reported by patients, which, in some cases, were not the usual doses. Patients also reported using doses of medicine on each application that were markedly lower than required. CONCLUSION: The QATOP is a valid and reliable self-report measure of adherence to topical treatment in patients with psoriasis. The use of this standard questionnaire could improve the methodological quality of adherence studies. Improvement of the clarity of posologic instructions is clearly urgently needed.

Emotion Regulation in Patients with Psoriasis: Correlates of Disability, Clinical Dimensions, and Psychopathology Symptoms.

PURPOSE: There are known connections between emotions and psoriasis; however, we have not established a clear pathway for this association. This study aimed to explore correlates of difficulties in emotional regulation in patients with psoriasis and predict the influence of emotional regulation in psoriasis disability. METHOD: Two hundred and twenty eight participants completed the Difficulties in Emotion Regulation Scale, Self-administered Psoriasis Area and Severity Index, Psoriasis Disability Index, and Brief Symptom Inventory. Spearman's correlation and a hierarchical stepwise multiple regression were carried out to analyse associations. RESULTS: Results indicated that patients with the most recent diagnoses experienced greater difficulty in acting in accordance with goals (r = .16, p < .05) but lesser difficulty in engaging in goal-directed behaviour (r = -.15, p < .05). Those with greater satisfaction with treatment exhibited fewer difficulties in emotional regulation (r = -.23, p < .01). The patients who experienced greater difficulty in emotional regulation perceived greater psoriasis severity (r = .15, p < .05) and disability (r = .36, p < .05), reported more psychopathological symptoms (correlations between .46 and .56), and missed work/school more frequently (r = .24, p < .05). Impulse control proved to be the strongest predictor to psoriasis disability (ß = .34). CONCLUSION: The results highlighted the relationship between emotional regulation difficulty, disease characteristics, and psychological variables in psoriasis disability emphasizing the importance of including a broader approach in clinical management of psoriatic patients.

Methodologies for medication adherence evaluation: Focus on psoriasis topical treatment.

Adherence to topical treatment has been less studied in comparison with systemic therapeutic regimens and is poorly understood. High-quality research on this area is essential to outline a strategy to increase medication adherence and clinical outcomes. For a more comprehensive understanding of this issue, a systematic review of the methodologies for topical treatment adherence evaluation in psoriasis was undertaken. Twenty one studies were selected from the literature which used six different adherence methodologies. Merely three studies used multiple adherence measurement methods. The most used method was questionnaire (44%) which was also associated with higher variability of the adherence results. One possible explanation is the lack of a validated questionnaire designed specifically for the evaluation of adherence to topical treatment. Only one method (medication weight) takes into consideration the applied dose. However, the estimation of the expected weight is complex, which renders this method, as used presently, less effective. The use of a dosing device could improve its accuracy and be helpful to clearly instruct the patients about the correct dose. As there is no single method that allows an accurate and complete assessment of adherence it is recommended to use a combination of methods, including self-report and medicines' weight measurements.

Development of noncytotoxic PLGA nanoparticles to improve the effect of a new inhibitor of p53-MDM2 interaction.

One possible approach to overcome solubility complications and enhance the biological activity of drugs is their incorporation into drug delivery systems. Within this scope, several nanosphere and nanocapsule formulations of a new inhibitor of p53-MDM2 interaction (xanthone 1) were developed and their physicochemical properties analyzed. Through the investigation of the effect of several empty nanoparticles on the growth of MCF-7 cells, it was possible to observe that four out of five formulations were cytotoxic and that some correlations between the toxic potential of these polymeric nanoparticles and their properties/composition could be extrapolated. One empty formulation of nanocapsules developed by emulsification/solvent evaporation and containing PLGA, PVA and Mygliol(®) 812 was found to be noncytotoxic to this cell line. The corresponding compound 1-loaded nanocapsules showed an incorporation efficiency of 77% and revealed to be more potent than the free drug against cell growth inhibition, which may be related to the enhancement in its intracellular delivery. In an integrative study, the intracellular uptake of nanocapsules was confirmed using fluorescent 6-coumarin and well as compound 1 release from nanocapsules. Overall, it was possible to enhance the effect of the hit inhibitor of p53-MDM2 interaction through the development of suitable noncytotoxic polymeric nanoparticles.

Development and validation of an HPLC method for the quantitation of 1,3-dihydroxy-2-methylxanthone in biodegradable nanoparticles.

A rapid and simple high-performance liquid chromatographic method for the analysis of 1,3-dihydroxy-2-methylxanthone (DHMXAN) in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanosphere and nanocapsule formulations is developed and validated. The method does not require any complex sample extraction procedure. Chromatographic separation is made with a reversed-phase C18 column, using methanol-water (90:10, v/v) containing 1% (v/v) acetic acid as a mobile phase at a flow rate of 1 mL/min. Identification is made by UV detection at 237 nm. The isocratic system operates at ambient temperature and requires 7.5 min of chromatographic time. The developed method is statistically validated according to ICH guidelines and USP 29 for its specificity, linearity, accuracy, and precision. The assay method proposed in this study is specific for DHMXAN in the presence of nanosphere and nanocapsule excipients. Diode-array analyses confirm the purity of DHMXAN peak in stress conditions (> 99.0%). The method is shown to be linear (r > or = 0.999) over the concentration range of 0.25-3.0 microg/mL. Recovery ranges from 99.0% to 102.7% (RSD: 1.49%) and from 98.3% to 101.6% (RSD: 1.07%) for nanospheres and nanocapsules, respectively. Repeatability (intra-assay precision) and intermediate precision is acceptable with RSD values ranging from 0.6% to 1.9% and from 0.3% to 2.0%, respectively. The method is shown to be suitable for the evaluation of DHMXAN content entrapped in PLGA nanoparticles.

Improvement of the inhibitory effect of xanthones on NO production by encapsulation in PLGA nanocapsules.

For the first time the inhibitory effect of xanthone and 3-methoxyxanthone on nitric oxide (NO) production by IFN-gamma/LPS activated J774 macrophage cell line is reported. A remarkable improvement of this effect promoted by encapsulation of these compounds in nanocapsules of poly (DL-lactide-co-glycolide) (PLGA) is also demonstrated. A weak inhibitory effect of 3.6% on NO production by activated macrophages was observed for xanthone at the highest studied concentration (100 microM). This effect was slightly higher for 3-methoxyxanthone at the same concentration, producing a reduction of 16.5% on NO production. In contrast, equivalent concentrations of xanthone and 3-methoxyxanthone incorporated in nanocapsules produced a significant decrease on NO production of 91.8 and 80.0%, respectively. Empty nanocapsules also exhibited a slight NO inhibitory activity, which may be due to the presence of soybean lecithin in the composition of the nanosystems. The viability of the macrophages was not affected either by free or nanoencapsulated xanthones. Fluorescence microscopy analysis confirmed that a phagocytic process was involved in the macrophage uptake of xanthone- and 3-methoxyxanthone-loaded PLGA nanocapsules. Phagocytosis might be the main mechanism responsible for the enhancement of the intracellular delivery of both compounds and consequently for the improvement of their biological effect.

Development and characterization of PLGA nanospheres and nanocapsules containing xanthone and 3-methoxyxanthone.

The aim of the present work was to develop and characterize two different nanosystems, nanospheres and nanocapsules, containing either xanthone (XAN) or 3-methoxyxanthone (3-MeOXAN), with the final goal of improving the delivery of these poorly water-soluble compounds. The xanthones-loaded nanospheres (nanomatrix systems) and nanocapsules (nanoreservoir systems), made of poly(DL-lactide-co-glycolide) (PLGA), were prepared by the solvent displacement technique. The following characteristics of nanoparticle formulations were determined: particle size and morphology, zeta potential, incorporation efficiency, thermal behaviour, in vitro release profiles and physical stability at 4 degrees C. The nanospheres had a mean diameter <170 nm, a narrow size distribution (polydispersity index <0.1), and a negative surface charge (zeta potential <-36 mV). Their incorporation efficiencies were 33% for XAN and 42% for 3-MeOXAN. The presence of the xanthones did not affect the nanospheres size and zeta potential. DSC studies indicated that XAN and 3-MeOXAN were dispersed at a molecular level within the polymeric nanomatrix. Nanocapsules were also nanometric (mean size <300 nm) and exhibited a negative charge (zeta potential <-36 mV). Their incorporation efficiency values (>77%) were higher than those corresponding to nanospheres for both xanthones. The release of 3-MeOXAN from nanocapsules was similar to that observed for the correspondent nanoemulsion, indicating that drug release is mainly governed by its partition between the oil core and the external aqueous medium. In contrast, the release of XAN from nanocapsules was significantly slower than from the nanoemulsion, a behaviour that suggests an interaction of the drug with the polymer. Nanocapsule formulations exhibited good physical stability at 4 degrees C during a 4-month period for XAN and during a 3-month period for 3-MeOXAN.

A validated HPLC method for the assay of xanthone and 3-methoxyxanthone in PLGA nanocapsules.

This work relates the development and validation of a simple reversed-phase high-performance liquid chromatographic (HPLC) method for the analysis of xanthone (XAN) and 3-methoxyxanthone (3-MeOXAN) in poly(D,L-lactide-co-glycolide) (PLGA) nanocapsule formulations. This method does not require any complex sample extraction procedure. Chromatographic separation is made with a reversed-phase C(18) column, using methanol-water (90:10, v/v) as a mobile phase at a flow rate of 1 mL/min. Identification is made by UV detection at 237 nm. The isocratic system operates at ambient temperature and requires 7 min of chromatographic time. The developed method is statistically validated according to United States Pharmacopoeia 25 and International Conference on Harmonization guidelines for its specificity, linearity, accuracy, and precision. The assay method proposed in this study is specific for XAN and 3-MeOXAN in the presence of nanocapsule excipients. Diode-array analyses confirm the homogeneity of XAN and 3-MeOXAN peaks in stressed conditions. Standard curves are linear (r > 0.999) over the concentration range of 0.4-2.5 and 1.0-5.8 micro g/mL for XAN and 3-MeOXAN, respectively. Recovery from nanocapsules ranges from 99.6% to 102.8% for XAN and 98.8% to 102.4% for 3-MeOXAN. Repeatability (intra-assay precision) is acceptable with relative standard deviation values of 1.2% for XAN and 0.3% for 3-MeOXAN.