Development and validation of a multivariable risk prediction model for serious infection in patients with psoriasis receiving systemic therapy.

BACKGROUND: Patients with psoriasis are often concerned about the risk of serious infection associated with systemic psoriasis treatments. OBJECTIVES: To develop and externally validate a prediction model for serious infection in patients with psoriasis within 1 year of starting systemic therapies. METHODS: The risk prediction model was developed using the British Association of Dermatologists Biologic Interventions Register (BADBIR), and the German Psoriasis Registry PsoBest was used as the validation dataset. Model discrimination and calibration were assessed internally and externally using the C-statistic, the calibration slope and the calibration in the large. RESULTS: Overall 175 (1·7%) out of 10 033 participants from BADBIR and 41 (1·7%) out of 2423 participants from PsoBest developed a serious infection within 1 year of therapy initiation. Selected predictors in a multiple logistic regression model included nine baseline covariates, and starting infliximab was the strongest predictor. Evaluation of model performance showed a bootstrap optimism-corrected C-statistic of 0·64 [95% confidence interval (CI) 0·60-0·69], calibration in the large of 0·02 (95% CI -0·14 to 0·17) and a calibration slope of 0·88 (95% CI 0·70-1·07), while external validation performance was poor, with C-statistic 0·52 (95% CI 0·42-0·62), calibration in the large 0·06 (95% CI -0·25 to 0·37) and calibration slope 0·36 (95% CI -0·24 to 0·97). CONCLUSIONS: We present the first results of the development of a multivariable prediction model. This model may help patients and dermatologists in the U.K. and the Republic of Ireland to identify modifiable risk factors and inform therapy choice in a shared decision-making process.

Linkage between patients' characteristics and prescribed systemic treatments for psoriasis: a semantic connectivity map analysis of the Swiss Dermatology Network for Targeted Therapies registry.

BACKGROUND: Several treatment options are currently available for the treatment of psoriasis. OBJECTIVE: To explore the main associations between patients' characteristics and systemic treatments prescribed for psoriasis in a large group of patients observed in real-life clinical practice. METHODS: This was a retrospective analysis of baseline data collected within the Swiss Dermatology Network for Targeted Therapies registry in Switzerland between March 2011 and December 2017. Semantic map analysis was used in order to capture the best associations between variables taking into account other covariates in the system. RESULTS: A total of 549 patients (mean age 46.7 ± 14.7 years) were included in the analysis. Conventional therapies such as retinoids and methotrexate were associated with no previous systemic therapies for psoriasis, a moderate quality of life (QoL) at therapy onset and older age (≥60 years). Fumaric acid derivatives were associated with mild psoriasis (psoriasis area severity index < 10) and long disease duration (≥20 years). On the other side, cyclosporine and psoralen and ultraviolet A/ultraviolet B treatments were linked to a more severe condition, including impaired QoL, hospitalization and inability to work. Regarding biological therapies, both infliximab and adalimumab were connected to the presence of psoriatic arthritis, severe disease condition and other comorbidities, including chronic liver or kidney diseases and tuberculosis. Etanercept, ustekinumab and secukinumab were all connected to a complex history of previous systemic treatments for psoriasis, moderate disease condition, overweight and university education. CONCLUSIONS: The analysis shows multifaceted associations between patients' characteristics, comorbidities, disease severity and systemic treatments prescribed for psoriasis. In particular, our semantic map indicates that comorbidities play a central role in decision-making of systemic treatments usage for psoriasis. Future studies should further investigate specific connections emerging from our data.

Psoriasis registries worldwide: systematic overview on registry publications.

BACKGROUND: Safety and efficacy of new treatments are analyzed in clinical trials but their capacity to show potential effects of long-term treatment and more than short latency of onset is limited. To meet this challenge, patient registries (of treatments or diseases) collect prospective data of real-world patients in daily practice without tight selection of patients. OBJECTIVE: The aim of this article was to identify existing psoriasis patient registries by published articles and evaluation of monitored treatment classes, patients, research questions addressed, and measurement instruments implemented. MATERIALS & METHODS: A systematic review of Medline (PubMed) and Embase (Ovid) databases for publications on psoriasis patient registries, including cross-validation was conducted October 2015. RESULTS: 14 patient registries for long-term observation of psoriasis patients in real-world care were identified. Registries were established since 2005, the majority is located in Europe. The number of published studies from single registries ranged from 1 to 10. Most registries include patients treated by conventional systemics as well as biologics. The number of patients analyzed ranged from 35 to >12 000 patients. The publications mostly addressed safety issues or treatment outcomes, followed by baseline description, drug survival, predictor analyses, and treatment patterns. CONCLUSION: A variety of local, national, and international patient registries collect longitudinal data on (systemic) psoriasis treatment. The number of publications reflect the main registry objectives of safety and effectiveness, with additional therapy-related investigations being addressed as well. Based on the information from publications, the combination of data from these registries will involve many methodological challenges. To gain comparability and combinability of cohorts and data across registries, further harmonization of data collection is demanded.

Effectiveness of advanced versus conventional wound dressings on healing of chronic wounds: systematic review and meta-analysis.

BACKGROUND: Wound dressings are essential in the treatment of chronic wounds and should be selected on valid and recent evidence. OBJECTIVE: Effectiveness of advanced compared to conventional dressings for chronic wound healing. METHODS: Comprehensive literature search, systematic review and meta-analyses of the results of advanced dressing studies on chronic wound treatment. Comprehensiveness and coverage of all relevant studies is the most striking difference in relation to other meta-analyses and systematic reviews. RESULTS: The mean odds ratio of complete healing was 1.52 favouring advanced over conventional dressings in 65 controlled trials. In 287 study conditions including uncontrolled studies, mean odds were 0.97 (advanced dressings/controlled studies), 0.77 (conventional/controlled) and 0.47 (advanced/uncontrolled). The overall healing rate was 33%. When causal treatment was applied, a reduced effect was observed. The consideration of all types of chronic wounds, advanced wound dressings and studies resulted in more study effects, more reliable estimates of mean effects and more statistical power. These differences in the design are likely to explain the differences in the meta-analytic results. CONCLUSION: A general superiority of advanced dressings on complete healing was shown. The generalizability of the results is limited by the methodological and report quality within studies identified, unexplained heterogeneity in study effects and possibly by publication bias.

Quality-of-care for leg ulcers in the metropolitan area of Hamburg--a community-based study.

BACKGROUND: Diagnosis and therapy of chronic wounds constitute an interdisciplinary challenge and should be oriented on the guideline standards. Although no data on the quality-of-care are available for Germany, it can be concluded from qualitative estimates and expert reports that the majority of patients are not receiving adequate treatment. OBJECTIVES: Evaluation of the quality-of-care for leg ulcers in the metropolitan area of Hamburg by means of newly developed guideline-based indicators. METHODS: Leg ulcer patients of any aetiology were consecutively included. The spectrum of 220 health-care providers ranged from wound clinics, office-based practices, nursing homes to home-care services and doss houses. The survey included a clinical examination and the completion of questionnaires covering quality of life, experiences with treatment and quality of health care. RESULTS: A total of 520 patients with leg ulcers were included. Among these patients, 63% were of venous, 23% of mixed, 2% of vasculitic and 12% of other origin; 78.6% of the patients were treated with moist wound dressings. Pain therapy was performed in 54.1%, compression therapy in 53.5%. Shortcomings were noted in the diagnostic work-up and in concomitant wound care such as physiotherapy. Around 70% displayed marked to profound impairment in quality of life. The quality-of-care index showed that 64% of the indicators were met by the actual care; 61.8% of the patients exhibiting a sufficient quality-of-care, regardless of age, social status, place of abode or insurance status. CONCLUSIONS: Although the majority of patients received adequate therapy, many patients are not being treated properly in accordance with the guidelines.

A new instrument for the assessment of patient-defined benefit in the treatment of allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a common disease that affects health-related quality of life (HRQoL). Current and future health policy demands the assessment of patient-relevant treatment benefit for evaluation of treatments. METHODS: We developed, validated and tested a standardized instrument for the assessment of patient-relevant needs and benefits in AR. In an open survey of patients with AR, 100 need and benefit items were generated. The items were condensed to a 25-item list by an expert panel. On this list, patient rates the personal importance of 25 treatment needs on a scale ranging from 'not at all' to 'very' before treatment (Patient Needs Questionnaire, PNQ). At the end of the treatment, patient rates the extent, to which these needs were achieved by treatment from 'did not help at all' to 'helped a lot' (Patient Benefit Questionnaire). The patient benefit index (PBI) is computed to provide a global weighted benefit parameter. This disease-specific instrument was validated in n = 104 patients with AR. RESULTS: The PBI-AR showed good acceptability and feasibility in clinical routine. Reduction in nose and eye symptoms was rated most important. The PBI amounted to 2.2 (PBI ranges from 0 = 'no benefit' to 4 = 'maximum benefit'). Reliability of the PNQ was high (Cronbach's alpha = 0.9).The PBI was significantly correlated with relevant external validation criteria, such as patient satisfaction (R = 0.54) and HRQoL (R = 0.26). CONCLUSION: The PBI-AR is a feasible, reliable and valid instrument for the standardized assessment of patient-relevant benefits in the treatment of AR.

Quality of life and satisfaction of patients with leg ulcers--results of a community-based study.

BACKGROUND: Leg ulcers have a major socio-economic impact because of their frequency and societal costs. Patients with leg ulcers experience major Health related Quality of Life (HrQoL) impairments. The aim of the present study was to assess the disease-specific HrQoL and the influence of care on HrQoL with leg ulcer. PATIENTS AND METHODS: A cross-sectional study was conducted in the metropolitan area of Hamburg to assess the quality of care as well as HrQoL in an unrestricted sample of patients with leg ulcers by questionnaires and subsequent clinical examinations. RESULTS: A total of 530 patients were consecutively recruited across all wound care provider sections in the metropolitan area of Hamburg. 53 % of the patients were highly or very satisfied with the health services provided. Significant correlations were found between the disease-specific HrQoL, patient satisfaction and satisfaction with wound treatment. Furthermore, significant predictors of HrQoL were: inadequate pain therapy, insurance status, wound size, time required for dressing changes and wound etiology. Most relevant predictors for satisfaction with health services were: HrQoL, duration of wound, health insurance status and treatment by office-based physicians. In contrast, no statistically significant association with HrQoL and satisfaction was found for gender, living district, education, number of dressing changes per week and the number of comorbidities. CONCLUSIONS: The results show that chronic leg ulceration has a major impact on patients HrQoL. Clinical and treatment characteristics, but not socio-demographic data, were predictors of HrQoL and satisfaction with health services. The systematic assessment of HrQoL in patients with leg ulcers across all sectors of health-care is a novum and provides important insights into the reality and quality of care.

[Epidemiology of psoriasis in Germany--analysis of secondary health insurance data]. / Epidemiologie der Psoriasis in Deutschland--Auswertung von Sekundärdaten einer gesetzlichen Krankenversicherung.

BACKGROUND: In Germany, population-based data on the epidemiology of psoriasis are still rare. This study aims to assess the prevalence of psoriasis in the total population as well as for subgroups relevant to health care. As further epidemiological parameters the severity and regional distribution of psoriasis were analysed. METHODS: A secondary analysis of data collected routinely for the members of a nationwide statutory health insurance company was conducted. Prevalences were calculated for a closed cohort of continuously insured persons in 2005. Defined criteria for the existence of psoriasis were at least one diagnoses of psoriasis (ICD-10) relating to ambulatory or hospital treatment or disability. RESULTS: 33,981 of the 1,344,071 continuously insured persons in 2005 were diagnosed with psoriasis, thus the one-year-prevalence in this cohort was 2.53%. Up to the age of 80 years the prevalence rate was increasing with increasing age and highest for the age groups from 50 to 79 years (range: 3.99-4.18%). Insured persons up to 20 years had a prevalence of 0.73%. Regional differences showed up after stratification for broad categories (1 digit) of ZIP codes: Lowest prevalence rates were seen in the south (2.17%) and highest (2.78%) in the north and western regions of Germany. CONCLUSIONS: If the prevalence rate of 2.5% assessed in this study is applied to the total resident population, 2 million people are treated because of psoriasis in Germany. Routine data from health insurance companies are a relevant and suitable data source to assess the prevalence of chronic diseases (under medical treatment) in the population.

[Registry research in dermatology]. / Registerforschung in der Dermatologie.

Patient registries are prospective, systematic data collections, which are non-interventional (observational) in nature and reflect care practices under routine conditions. As a result, they include the most common disease characteristics (e.g. in cancer registries) and/or medical interventions (e.g. in therapy registries). The importance of registries in health services research and in clinical medicine is rapidly increasing. This is due to increasingly scarce resources in the health system and the growing need for data on benefits and efficiency. Registries permit evaluation long-term outcomes on e.g. quality of life, effectiveness as well as treatment quality. An overview of registry methodology from definitions to data analysis is given, existing registries in dermatology in Germany are summarized.

[Memorandum registry for health services research]. / Memorandum Register für die Versorgungsforschung.

On August 30, 2010, the German Network for Health Services Research [Deutsches Netzwerk Versorgungsforschung e. V. (DNVF e. V.)] approved the Memorandum III "Methods for Health Services Research", supported by their member societies mentioned as authors and published in this Journal [Gesundheitswesen 2010; 72: 739-748]. Registries in Health Services Research vary in their aims and research questions as well as in their designs, methods of data collection, and statistical analyses. This paper aims to provide both a methodological guideline for developers to ensure a high quality of a planned registry and, to provide an instrument for users of data from registries to assess their overall quality. First, the paper provides a definition of registries and presents an overview of objectives in Health Services Research where registries can be useful. Second, several areas of methodological importance for the development of registries are presented. This includes the different phases of a registry (i. e., conceptual and preliminary design, implementation), technical organisation of a registry, statistical analysis, reporting of results, data protection, and ethical/legal aspects. From these areas, several criteria are deduced to allow the assessment of the quality of a registry. Finally, a checklist to assess a registry's quality is presented.

Measuring patient-relevant benefits in pruritus treatment: development and validation of a specific outcomes tool.

BACKGROUND: The assessment of patient-relevant benefit is gaining importance in evaluating treatments. The 'Patient Benefit Index, standard version' questionnaire (PBI-S) is a validated instrument to assess patients' treatment needs and benefits in skin diseases. Before therapy, the patient rates the importance of predefined treatment goals; after therapy, he rates the extent to which these goals have been achieved. Thus far, no such instrument has been developed specifically for pruritus. OBJECTIVES: Development and validation of a patient-relevant benefit questionnaire in the treatment of pruritus. METHODS: Fifty patients with pruritus were questioned on impairments due to pruritus and treatment needs. Four treatment objectives not already covered by the PBI-S were added to obtain a disease-specific instrument. This was tested for feasibility by 36 patients with pruritus and validated in a sample of 100 patients with pruritus. RESULTS: The instrument was feasible in clinical practice. There were < 2% missing values. Cronbach's alpha of the needs questionnaire was 0.93. Convergent validity was demonstrated with respect to reduction of pruritus and quality of life. CONCLUSIONS: The PBI for pruritus is a feasible, reliable and valid instrument that is highly accepted in daily routine for recording patient-reported benefit.

Assessing the value of supportive skin care: development and validation of an instrument for evaluating patient-relevant benefit.

BACKGROUND: Supportive skin care for irritated and inflamed skin is one of the most important measures in the prevention and treatment of eczema and sensitive skin. OBJECTIVES: To develop and validate an instrument for the evaluation of patient-relevant benefit in the supportive care of irritated skin with nonpharmacological topical agents. METHODS: Patient-defined treatment objectives and benefits of supportive skin care were determined in an open survey of patients with irritated skin. A pilot questionnaire was constructed according to the Patient Benefit Index (PBI). The questionnaire was tested for feasibility and validity in 1,886 patients with various irritated skin conditions. RESULTS: From a total of 90 characteristics of basic therapy benefit, a 23-item questionnaire was constructed. This questionnaire ('PBI-k') proved to be feasible, reliable and was associated with a high level of patient acceptance in the surveillance field. The questionnaire showed good internal consistency, distribution characteristics and convergent validity with patient satisfaction. CONCLUSION: The PBI-k is the first specific instrument developed for the evaluation of patient-defined benefit in supportive skin care with nonpharmacological topical agents. Feasibility and psychometric properties make this questionnaire suitable for application in studies involving patients with irritated, sensitive skin.

Evaluation of quality of care and guideline-compliant treatment in psoriasis. Development of a new system of quality indicators.

BACKGROUND: To date, no standardised indicators for quality of care in psoriasis have been published. AIMS: Development and testing of evidence-based indicators of quality of care and guideline compliance in the treatment of psoriasis. METHODS: Indicators of process and outcome quality were extracted and evaluated in a Delphi process according to international standards. The primary reference was the S3 German guideline for psoriasis treatment. The indicators were validated with data from two nationwide studies on psoriasis care involving 1,511 and 2,009 patients. RESULTS: Eight quality indicators were defined: mean PASI, mean quality of life (Dermatology Life Quality Index; DLQI), proportion of patients with PASI >20, with DLQI >10, with previous systemic treatment, with PASI >20 and systemic treatment, with inpatient treatment, and number of work days lost. All indicators proved suitable for application, and were sensitive to change. CONCLUSIONS: Guideline-based indicators of quality of care are useful in the analysis of health care and the implementation of treatment guidelines in psoriasis.

[Efficacy and patient benefit of treatment of irritated skin with ointments containing dexpanthenol: health services research (observational study) on self-medication in a pharmaceutical network]. / Patientennutzen und Anwendungsmerkmale der Behandlung irritierter Haut mit dexpanthenolhaltiger Salbe: Versorgungsstudie (Anwendungsbeobachtung) zur Selbstmedikation in einem Apothekennetzwerk.

BACKGROUND: Products containing dexpanthenol are used to treat irritated and inflamed skin. So far there is a lack of data for the evidence of patient-relevant benefits. OBJECTIVE: Assessment of the patient-relevant benefit of ointments containing dexpanthenol in the self-medicated therapy of irritated skin. METHODS: Prospective, observational study in a network of 392 pharmacies. Consecutive recruitment of n=1,886 patients with symptoms of irritated skin, including non-inflammatory intervals of atopic eczema, other xerotic skin conditions and impairment of skin barrier. The patient-relevant benefit was ascertained prior to and 7-10 days after treatment through the patient-benefit index (PBI). RESULTS: The PBI showed that 91.5% of the patients experienced a relevant benefit from treatment. 94.7% directly indicated to have had achieved successful therapeutic results. All symptoms of irritated skin (e.g. xerosis, erythema, desquamation) significantly improved (p

Prevalence of skin diseases in a cohort of 48,665 employees in Germany.

BACKGROUND: Epidemiological data are important for planning medical care. Thus far, only few prevalence data for skin diseases have been published in Germany, most of them not population based. OBJECTIVES: Estimation of prevalences of common skin diseases in a sample of employees of German companies. METHODS: Whole-body examinations were performed by trained dermatologists in 150 companies as part of skin cancer screenings. Using a standardized and computerized data entry, all clinical dermatological findings were documented. Explicitly skin lesions requiring current treatment were noted. The retrospective evaluation of the data was descriptive, using the diagnoses defined a priori in the data entry mask. RESULTS: 48,665 persons (52.8% male) with a mean age of 43.2 years were examined. The following frequencies of chronic and acute inflammatory skin diseases were observed: contact eczema 8.9%, acne 4.2%, seborrhoeic eczema 3.4%, rosacea 2.2%, psoriasis vulgaris 2.1%, atopic eczema 1.4% and lichen ruber 0.07%. In total, dermatological findings needing treatment were observed in 19% of the study cohort; 1.3% of the participants presented a suspicious finding requiring diagnostics for skin malignoma. CONCLUSIONS: There is a high frequency of chronic inflammatory skin diseases in the general working population and a high need for dermatological treatment.

Benefit evaluation in vitiligo treatment: development and validation of a patient-defined outcome questionnaire.

BACKGROUND: In addition to clinical efficacy, patient-defined benefit assessment has become an important outcome parameter. Thus far, no such instrument has been developed for vitiligo. OBJECTIVES: Development and validation of a patient-defined benefit questionnaire in the therapy of vitiligo. METHODS: Open questioning of 50 vitiligo patients generated 110 benefit items, which were converted into a 26-item questionnaire by a panel of dermatologists, psychologists and patients. This was used to record patient-defined needs prior to therapy and to evaluate patient benefit attained after therapy. A 'patient benefit index' (PBI) was formed on the basis of both. Validation was based on data of n = 1,023 vitiligo patients. RESULTS: The questionnaires were feasible in clinical practice, Cronbach's alpha (patient need questionnaire) was 0.94. The PBI showed convergent and discriminant validity with respect to quality of life and patient satisfaction. CONCLUSION: The PBI for vitiligo is a valid instrument, which is highly accepted in practice for recording patient-reported benefit.

Drug safety of systemic treatments for psoriasis: results from The German Psoriasis Registry PsoBest.

The German Psoriasis Registry PsoBest was conducted in 2008 in order to investigate the long-term outcomes and safety of systemic treatments for moderate-to-severe psoriasis. Safety analysis of antipsoriatic drugs with special focus on serious adverse events (SAE) for infections, malignancies and major cardiac events (MACE) was done. Nationwide non-interventional patient treatment registry conducted in 251 active dermatology centers. Until June 2012, n = 2444 patients [40 % female; mean age 47.3 (SD 14.1) years; mean duration of disease 18.2 (SD 14.7) years] were recruited, including n = 1791 patients (3842 patient years) with conventional systemic drugs and n = 908 (3442 patient years) with biological drugs. Mean PASI (Psoriasis Area and Severity Index) at inclusion was 14.7, mean DLQI (Dermatology Life Quality Index) 11.1, mean BMI (Body Mass Index) 28.2. The overall rate of SAE per 100 patient years were 1.3 (SD 0.9) per 100 patient years in conventional systemic and 1.5 (SD 1.2) in biologics (p > 0.5, no significant difference). The rates per 100 patient years for single severe adverse events were as follows (systemic/biologics): serious infections, 0.33/0.65 [CI (confidence interval) 0.13-0.54/0.35-0.98]; MACE, 0.56/0.77 (CI 0.29-0.97/0.41-1.31); malignancies (except non-melanoma skin cancer), 0.46/0.49 (CI 0.22-0.84/0.21-0.97). There were no significant differences between single drugs in any of the safety parameters. The conventional systemic and biologic drugs for psoriasis show satisfying safety under routine psoriasis care in Germany with respect to infections, MACE and malignancies.