The challenges of assessing patients' medication beliefs: a qualitative study

Background An estimated 50% of patients do not take their medication as prescribed, with medication adherence associated with adverse outcomes and higher costs of care. The Necessity-Concerns Framework identified individual’s beliefs about their medication as playing a key role in adherence, and UK Clinical Adherence Guidelines recommend eliciting and incorporating individual’s perceptions of their medication within the consultation. The Beliefs about Medicines Questionnaire (BMQ) is widely used to assess medication beliefs, however, given the condition-specific nature of some self-management regimens, it is unknown whether this tool is able to fully capture beliefs about more complex medication regimens. Methods We examined the challenges of assessing medication beliefs using the BMQ in 20 people with a complex relapsing-remitting condition recruited from community sources. Data were collected from people with psoriasis; a patient group characterised by complex medication regimens, which include therapies that are applied topically, phototherapy/photochemotherapy, and therapies that are administered orally or via subcutaneous or intravenous injections. Semi-structured cognitive interviews were undertaken, with responses coded using established schedules and analysed using Content analysis. Results Individual’s beliefs about their condition specific therapies were not accurately captured by the BMQ. Medication beliefs as expressed during ‘real-time’ completion of the BMQ were underestimated, or failed to be captured, by the corresponding scores given by participants. There was mismatch between the terminology used in the scale and individuals perceptions of their condition and the complexity of its management and treatment outcomes. Currently the BMQ cannot represent beliefs about medicines underuse, even though some individuals with psoriasis viewed access to therapies as overly restrictive. Some the BMQ items were misinterpreted in part due to ambiguous item wording or due to misreading by participants. Conclusions This is the first study to identify general and condition-specific difficulties experienced by individuals completing the BMQ in ‘real time’. The main implication of this research is the need to develop condition-specific versions of the BMQ in order that this important instrument can capture the full range of medication beliefs in individuals living with a complex relapsing-remitting condition. Access to condition-specific versions could significantly increase our understanding of beliefs which facilitate or reduce medication adherence

Lymphocyte Trafficking in Psoriasis: A New Perspective Emphasizing the Dermal Dendrocyte with Active Dermal Recruitment Mediated Via Endothelial Cells Followed by Intra-Epidermal T-Cell Activation

Prominent within the inflammatory infiltrate of psoriasis are HLA-DR positive T lymphocytes and factor XIIIa positive dermal dendrocytes. Many investigators studying psoriasis have assumed that the HLA-DR positive T cells are activated, and thereby capable of producing lymphokines such as gamma interferon. However, by immunohistochemical analysis, greater than 95% of the dermal T cells in psoriatic lesions are Ki-67 negative, which suggests that they are in a resting or non-cycling (Go) state. In contrast to the darmal T-cell population, the epidermal T-cell population contains a greater population of Ki-67 positive lymphocytes. The entry of the T cells into the epidermis is, therefore, apparently associated with an important activation event, which in all likelihood involves interaction with the keratinocyte. The presence of activated intraepidermal T cells has been substantiated by the ability to detect gamma interferon mRNA by polymerase chain reaction in epidermal sheets of psoriatic lesions. The pathophysiologic implication in psoriasis for these distinctions and compartmentalization involving dermal and epidermal T cells are placed into the context of a cascade of cellular trafficking events, which are further dissected into a specific network of molecular mediators of inflammation. This report suggests that more attention should be placed on the microenvironment of the skin, with specific emphasis on the mechanism by which T cells accumulate in the dermis and epidermis, and elucidation of the selective inductive and recruitment capabilities of endothelial cells, perivascular dermal dendrocytes, and keratinocytes

Fibrillin-Rich Microfibrils are Reduced in Photoaged Skin. Distribution at the Dermal–Epidermal Junction

Chronic sun exposure results in photoaged skin with deep coarse wrinkles and loss of elasticity. We have examined the distribution and abundance of fibrillin-rich microfibrils, key structural components of the elastic fiber network, in photoaged and photoprotected skin. Punch biopsies taken from photoaged forearm and from photoprotected hip and upper inner arm of 16 subjects with a clinical range of photoaging were examined for fibrillin-1 and fibrillin-2 expression and microfibril distribution. In situ hybridization revealed decreased fibrillin-1 mRNA but unchanged fibrillin-2 mRNA levels in severely photoaged forearm biopsies relative to photoprotected dermal sites. An immunohistochemical approach demonstrated that microfibrils at the dermal–epidermal junction were significantly reduced in moderate to severely photoaged forearm skin. Confocal microscopy revealed that the papillary dermal microfibrillar network was truncated and depleted in photoaged skin. These studies highlight that the fibrillin-rich microfibrillar network associated with the upper dermis undergoes extensive remodeling following solar irradiation. These changes may contribute to the clinical features of photoaging, such as wrinkle formation and loss of elasticity

Impaired Langerhans cell migration in psoriasis

We have examined whether psoriasis is associated with systemic effects on epidermal Langerhans cell (LC) function and, specifically, the migration of LCs from the skin. Compared with normal skin, the frequency and morphology of epidermal LCs in uninvolved skin from patients with psoriasis was normal. However, mobilization of these cells in response to stimuli that normally induce migration (chemical allergen, tumor necrosis factor α [TNF-α], and interleukin-1β [IL-1β]) was largely absent, despite the fact that treatment with TNF-α and IL-1β was associated with comparable inflammatory reactions in patients and controls. The failure of LC migration from uninvolved skin was not attributable to altered expression of receptors for IL-1β or TNF-α that are required for mobilization, nor was there an association with induced cutaneous cytokine expression. Although a role for altered dynamics of LC migration/turnover has not been formally excluded, these data reveal a very consistent decrement of LC function in psoriasis that may play a decisive role in disease pathogenesis

Severely Photosensitive Psoriasis: A Phenotypically Defined Patient Subset

A subset of patients with chronic plaque psoriasis exhibits severely photosensitive psoriasis (PP) with a pronounced seasonal pattern, but the pathomechanism is not understood. We performed two related studies; first, a detailed clinical characterization of PP, and second, a controlled investigation exploring the underlying pathomechanisms through the assessment of disease onset after photoprovocation. Patients with PP (n=20) showed striking female predominance (19F:1M), very low mean age of psoriasis onset (11 years, range 2–24), family history of psoriasis (13/20), a strong HLA–Cw*0602 association (16/17), and a rapid abnormal clinical response to broadband UVA, comprising erythema±scaling plaques (17/20). Subsequently, patients with PP (n=10), non-PP (n=9), and healthy volunteers (n=11) were challenged with low-dose broadband UVA on 3 consecutive days, and serial biopsies were taken after 6hours to 7 days and from unchallenged skin. Histological changes consistent with early psoriasis occurred in 4 of 10 PP patients, but in neither of the control groups, with significant dermal infiltration by neutrophils, CD4+, CD8+, and CD45RO+ cells at 24h, accompanied by acanthosis. Thus, a phenotypically distinct subset of psoriasis has been characterized. In contrast with earlier assumptions, UV can provoke psoriasiform features rapidly de novo; a role for memory effector T cells is supported in the early phase

Differential Regulation of Tyrosinase Activity in Skin of White and Black Individuals In Vivo by Topical Retinoic Acid

Tyrosinase activity is a key determinant of melanin production in skin. Because retinoic acid regulates tyrosinase activity in melanoma cells, we analyzed modulation of pigmentation in vivo by retinoic acid. Black and white subjects were either not treated, or treated topically for 4 d under occlusion with vehicle, retinoic acid (0.1%), or the irritant sodium lauryl sulfate (2%). In untreated skin, tyrosinase activity and melanin content were significantly greater (2.3 times, and 3.2 times, respectively) in blacks versus whites. Four days of treatment with topical retinoic acid did not alter tyrosinase activity or melanin content in black skin. In contrast, retinoic acid treatment significantly induced (2.7 times, n = 8) tyrosinase activity, compared to vehicle treatment, in white skin. Melanin content, however, remained unchanged at 4 d. In separate experiments, tyrosinase activity in white subjects (n = 25) was increased 16% (p = 0.01) in sodium lauryl sulfate – treated skin, and 77% (p = 0.0005) in retinoic acid – treated skin, compared to vehicle-treated skin. The effect of retinoic acid on tyrosinase activity could be differentiated from non-specific irritation, because tyrosinase activity in retinoic acid – treated skin was significantly greater (52%, p = 0.004) than sodium lauryl sulfate-treated skin. Similar results were obtained with the dihydroxyphenylalanine reaction done on vehicle, sodium lauryl sulfate-, and retinoic acid – treated white skin. Northern analysis (n = 6) and semi-quantitative polymerase chain reaction (n = 6) demonstrated that retinoic acid treatment did not alter tyrosinase mRNA levels in white skin. Western analysis revealed that induction of tyrosinase activity by retinoic acid also was not associated with increased tyrosinase protein content (n = 9), indicating that regulation of tyrosinase activity by retinoic acid occurs through a post-translational mechanism. These data demonstrate that low tyrosinase activity in white skin in vivio is retinoic acid inducible and high tyrosinase activity in black skin in vivo is neither further induced nor reduced by retinoic aci

Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1)

BackgroundApremilast works intracellularly to regulate inflammatory mediators.ObjectiveESTEEM 1 evaluated efficacy/safety of apremilast at 30 mg twice a day for moderate to severe plaque psoriasis.MethodsThis phase III, multicenter, double-blind, placebo-controlled study randomized adults (2:1) to apremilast or placebo. At week 16, the placebo group switched to apremilast through week 32, followed by a randomized treatment withdrawal phase to week 52. Binary end points were analyzed using χ2 test; continuous end points used analysis of covariance.ResultsIn all, 844 patients were randomized (n = 282, placebo; n = 562, apremilast). At week 16, significantly more patients taking apremilast achieved 75% or greater reduction from baseline Psoriasis Area and Severity Index score (PASI-75) (33.1%) versus placebo (5.3%, P < .0001; primary end point). Most (61.0%) patients rerandomized to apremilast at week 32 achieved PASI-75 at week 52 versus 11.7% rerandomized to placebo. Of patients rerandomized to apremilast at week 32, mean percentage change from baseline PASI score was −88% to −81% (weeks 32-52). During the placebo-controlled period, 55.7% and 69.3% of patients randomized to placebo and apremilast, respectively, had 1 or more adverse events. Most adverse events were mild/moderate in severity. No new significant adverse events emerged with continued apremilast exposure versus the placebo-controlled period.LimitationsData were limited to 52 weeks and may not generalize to nonplaque psoriasis.ConclusionsApremilast was effective in moderate to severe plaque psoriasis

Implementation of the PsoWell™ model for the management of people with complex psoriasis

The Psoriasis and Well-being (PsoWell)™ training programme, incorporating motivational interviewing, improves clinicians’ knowledge and skills to manage complex psoriasis, including behaviour change. The aims of this study were to deliver the PsoWell™ training programme to dermatology specialists, and to evaluate the acceptability and feasibility of implementing the PsoWell™ model across dermatology services. Framework analysis of 19 qualitative semi-structured interviews was performed, following delivery of nine, 1-day PsoWell™ training days involving 119 participants. Two themes were identified: “Perceptions and Priorities” and “Awareness”, sub-divided into: “Awareness Not Competence” and “Increasing Awareness”. The PsoWell™ model was found to be acceptable and feasible to implement across dermatology settings. Participants were more skilled and motivated to address psycho­logical issues, including behaviour change, but wanted further training to ensure competency. The trainees claimed that scepticism among some colleagues regarding whole-patient management might prevent uptake. Data show­ing the impact on health outcomes are needed and might overcome scepticism. Remote consultation could adopt the PsoWell™ approach