No Placebo Effect beyond Regression to the Mean on the Six Minute Walk Test in Pulmonary Arterial Hypertension Trials.

In drug studies, patients are often included when the disease activity is high. This will make any treatment appear to lessen disease activity, although the improvement is biased by selection. This effect is known as regression towards the mean (RTM). We aimed at investigating drug trials in Pulmonary Arterial Hypertension (PAH) using the 6-minute walking distance test (6MWD) as a primary outcome for the phenomenon of RTM. An existing registry of 43 open label studies and 23 randomized controlled trials conducted between 1990 and 2009 was used as the data source. Data analysis was carried out for 18 randomized controlled trials (RCTs) and 24 open label studies out of this registry. Data were analyzed for verum and placebo arms of the RCTs separately, as well as for the open label arms. In the verum arms, the overall effect given as 33.2 m (95% CI: 25.7; 40.6]); 6MWD was slightly lower than the effect in the observational studies, with 44.6 m (95% CI: [25.4; 63.8]). After studying and interpreting the data, we found that regression towards the mean plays only a minor role in PAH studies. In particular, placebo effects in the RCTs were negligibly small, with a mean 6MWD of -2.5 m (95% CI: [-9.8; 4.7]) in the placebo arm. Therefore, our analysis indicates that results of non-randomized observational studies can be regarded as valid tools for gaining valid clinical effects in patients with PAH.

Information technology and changing role models in German libraries: The example of OPEN-CAM.

Germany has a long tradition of health libraries. From their origin in monasteries, they became centres of knowledge and education. In modern times, this tradition has been continued by the Central Library of Medicine. In addition, as a specialty in Germany, special collection areas and special libraries that focus on one topic were established. Those services were transformed to specialized information services and portals as part of the digital transformation process. One of such projects is OPEN-CAM, which provides literature on integrative medicine in a specialist library and hosts the literature database CAMbase. Based on this example, we show how digital transformation has influenced the library landscape and its structures in Germany.

Association of patients' pre-therapy strengths and alliance in outpatient psychotherapy: A multilevel growth curve analysis.

OBJECTIVE: Meta-analytic evidence showed robust associations between the alliance in psychotherapeutic dyads and treatment outcomes. Recent studies have indicated that facets of positive mental health are additionally relevant predictors of both the alliance and success of psychotherapy. However, the impact of patients' pre-therapy strengths on the alliance at the beginning and during treatment has been scarcely examined. METHOD: 428 patients (62.4% female, Mage = 40.79), treated by 41 therapists, underwent cognitive behavioral therapy in a German outpatient training and research center. Alliance from patients' perspectives was assessed at the beginning and during treatment. Data were analyzed with multilevel growth curve modeling. RESULTS: Alliance increased during psychotherapy, with a quadratic trajectory best representing this trend on average, p < .001. Pre-therapy strengths were positively related to alliance intercept, b = 0.0537, p < .001. No interaction was found between the included time variables and pre-therapy strengths in the prediction of the alliance slope. CONCLUSION: Positive mental health facets should be considered in psychotherapy research and practice. Future studies may focus on the parallel development of patients' strengths with other process factors in treatment.

Profiles and predictors of healthcare utilization: using a cluster-analytic approach to identify typical users across conventional, allied and complementary medicine, and self-care.

INTRODUCTION: The identification of typologies of health care users and their specific characteristics can be performed using cluster analysis. This statistical approach aggregates similar users based on their common health-related behavior. This study aims to examine health care utilization patterns using cluster analysis; and the associations of health care user types with sociodemographic, health-related and health-system related factors. METHODS: Cross-sectional data from the 2012 National Health Interview Survey were used. Health care utilization was measured by consultations with a variety of medical, allied and complementary health practitioners or the use of several interventions (exercise, diet, supplementation etc.) within the past 12 months (used vs. not used). A model-based clustering approach based on finite normal mixture modelling, and several indices of cluster fit were determined. Health care utilization within the cluster was analyzed descriptively, and independent predictors of belonging to the respective clusters were analyzed using logistic regression models including sociodemographic, health- and health insurance-related factors. RESULTS: Nine distinct health care user types were identified, ranging from nearly non-use of health care modalities to over-utilization of medical, allied and complementary health care. Several sociodemographic and health-related characteristics were predictive of belonging to the respective health care user types, including age, gender, health status, education, income, ethnicity, and health care coverage. CONCLUSIONS: Cluster analysis can be used to identify typical health care utilization patterns based on empirical data; and those typologies are related to a variety of sociodemographic and health-related characteristics. These findings on individual differences regarding health care access and utilization can inform future health care research and policy regarding how to improve accessibility of different medical approaches.

Dysregulated Retinoic Acid Signaling in the Pathogenesis of Pseudoexfoliation Syndrome.

Pseudoexfoliation (PEX) syndrome, a stress-induced fibrotic matrix process, is the most common recognizable cause of open-angle glaucoma worldwide. The recent identification of PEX-associated gene variants uncovered the vitamin A metabolic pathway as a factor influencing the risk of disease. In this study, we analyzed the role of the retinoic acid (RA) signaling pathway in the PEX-associated matrix metabolism and evaluated its targeting as a potential candidate for an anti-fibrotic intervention. We provided evidence that decreased expression levels of RA pathway components and diminished RA signaling activity occur in an antagonistic crosstalk with TGF-ß1/Smad signaling in ocular tissues and cells from PEX patients when compared with age-matched controls. Genetic and pharmacologic modes of RA pathway inhibition induced the expression and production of PEX-associated matrix components by disease-relevant cell culture models in vitro. Conversely, RA signaling pathway activation by natural and synthetic retinoids was able to suppress PEX-associated matrix production and formation of microfibrillar networks via antagonization of Smad-dependent TGF-ß1 signaling. The findings indicate that deficient RA signaling in conjunction with hyperactivated TGF-ß1/Smad signaling is a driver of PEX-associated fibrosis, and that restoration of RA signaling may be a promising strategy for anti-fibrotic intervention in patients with PEX syndrome and glaucoma.

Lipid transfer protein allergy: characterization and comparison to birch-related food allergy.

BACKGROUND: Lipid transfer proteins (LTP) are a frequent elicitor of anaphylaxis to plant-derived food allergens in southern Europe. PATIENTS AND METHODS: 15 German patients with LTP allergy were compared to 17 patients with birch-related food allergy (BRFA) using a detailed anamnesis, serology, skin tests, and the FAQLQ-AF quality of life questionnaire. RESULTS: While patients with BRFA mainly reacted to tree nuts, and pome and stone fruits, LTP allergic individuals reported vegetables, berry fruits, cereals, and seeds as common additional elicitors. Anaphylaxis was associated with cofactors in 73 % of LTP allergic patients compared to only 6 % in BRFA (P < 0.001). Symptoms occurred delayed by more than one hour in 40 % and were triggered by raw and cooked foodstuffs in 86 % of LTP allergic patients, compared to only 6 % and 41 % of BRFA patients, respectively. A peach prick test was positive in all LTP allergic patients, but only in 15 % of BRFA patients (P < 0.001). Although patients with LTP allergy reported severe anaphylaxis more frequently, quality of life did not differ between groups. CONCLUSIONS: Anaphylaxis to plant-derived foodstuffs warrants assessment by IgE detection to Pru p 3 and skin tests with peach extract, particularly if cofactors and intolerance to heated foodstuffs are related.

Medical error analysis in dermatology according to the reports of the North Rhine Medical Association from 2004 to 2018.

BACKGROUND: Assessment of complaints addressed to the Expert Committee for Medical Malpractice Claims of the North Rhine Medical Association helps to identify quality assurance problems in dermatology. METHODS: 333 dermatological reports (years 2004-2018) were allocated to three five-year intervals in order to show changes of total number of reports and with regard to indications, types of care, defined diagnosis categories, and therapeutic interventions. Statistical analysis was mainly descriptive (SPSS 27). Representative cases are explained in more detail. RESULTS: The number of dermatological reports fell from 119 in the first to 92 reports in the last five-year interval, along with a decline in treatment error rates (43 % and 29 %) despite an increasing number of procedures across disciplines. 104 reports dealt with (supposed) diagnostic errors, 156 with physical or pharmacological therapies, and 73 reports with surgery. The latter had a low treatment error rate (29 %). CONCLUSIONS: In comparison to the number of dermatological treatments in Germany, patient allegations are raised only rarely indicating greater patient satisfaction and/or a lower risk potential in dermatology. Incorrect dosages or device settings, diagnostic errors, and deficits in obtaining informed consent are relevant sources of error as underlined by the presented case reports.

Adverse events and contradictory effects of benzodiazepine in a case with intellectual disability and challenging behaviour.

This study aims to contribute to the knowledge about lacking or contradictory effects of benzodiazepine on hyperaroused or aggressive behaviour in persons with intellectual disability (ID). We conducted a retrospective and natural case study in a person with mild ID and multiple adverse childhood experiences (ACE), using routine diary data consisting of 275 days including 113 consecutive days under benzodiazepine medication. The medication effects were documented as "calm / relaxed", "fretful / distressed" and "sleep / doze". Transitions between these were modelled using Markov chains. Differences in transitions were analysed using Chi-Square test for homogeneity. The results show a significantly reduced stability of mood and increased distressed behaviour under benzodiazepine. This is in line with reports about the effects of psychotropic medication in patients with ID and challenging behaviour. Besides other influences on unexpected medication effects, a possible dissociative identity disorder is discussed as an additional explanation.

The INTREST registry: protocol of a multicenter prospective cohort study of predictors of women's response to integrative breast cancer treatment.

BACKGROUND: Cancer registries usually assess data of conventional treatments and/or patient survival. Beyond that, little is known about the influence of other predictors of treatment response related to the use of complementary therapies (CM) and lifestyle factors affecting patients' quality and quantity of life. METHODS: INTREST is a prospective cohort study collecting register data at multiple German certified cancer centers, which provide individualized, integrative, in- and outpatient breast cancer care. Patient-reported outcomes and clinical cancer data of anticipated N = 715 women with pTNM stage I-III breast cancer are collected using standardized case report forms at the time of diagnosis, after completing neo-/adjuvant chemotherapy, after completing adjuvant therapy (with the exception of endocrine therapy) as well as 1, 2, 5, and 10 years after baseline. Endpoints for multivariable prediction models are quality of life, fatigue, treatment adherence, and progression-based outcomes/survival. Predictors include the study center, sociodemographic characteristics, histologic cancer and comorbidity data, performance status, stress perception, depression, anxiety, sleep quality, spirituality, social support, physical activity, diet behavior, type of conventional treatments, use of and belief in CM treatments, and participation in a clinical trial. Safety is recorded following the Common Terminology Criteria for Adverse Events. DISCUSSION: This trial is currently recruiting participants. Future analyses will allow to identify predictors of short- and long-term response to integrative breast cancer treatment in women, which, in turn, may improve cancer care as well as quality and quantity of life with cancer. TRIAL REGISTRATION: German Clinical Trial Register DRKS00014852 . Retrospectively registered at July 4th, 2018.

Cost-effectiveness analysis for SilAtro-5-90 adjuvant treatment in the management of recurrent tonsillitis, compared with usual care only.

PURPOSE: Antibiotics are one possible treatment for patients with recurrent acute throat infections (ATI), but effectiveness can be modest. In view of worries over antibiotic resistance, treatment pathways that reduce recurrence of ATI are essential from a public health perspective. Integrative treatment strategies can be an option but there is still a high demand to provide evidence of their cost effectiveness. METHODS: We constructed a 4-state Markov model to compare the cost-effectiveness of SilAtro-5-90 as adjuvant homeopathic therapy to care as usual with care as usual alone in reducing the recurrence of ATI for children and adults with suspected moderate recurrent tonsillitis. The analysis was performed from a societal perspective in Germany over a 2-year period. Results are reported separately for children < 12 and for individuals aged 12 and over. The model draws on evidence from a multi-centre randomised clinical trial that found this strategy effective in reducing recurrence of ATI. Costs in 2019 € and outcomes after 1 year are discounted at a rate of 3% per annum. RESULTS: For adults and adolescents aged 12 years and over, incremental cost per ATI averted in the adjuvant therapy group was €156.64. If individuals enter the model on average with a history of 3.33 previous ATIs, adjuvant therapy has both lower costs and better outcomes than care as usual. For children (< 12 years) adjuvant therapy had both lower costs and ATI than care as usual. The economic case is stronger if adjuvant treatment reduces surgical referral. At a hypothetical cost per ATI averted threshold of €1000 probabilistic sensitivity analysis suggests Silatro-5-90 has a 65% (adults) and 71% (children) chance of being cost-effective. CONCLUSION: Our results indicate the importance of considering homeopathy as adjuvant therapy in the treatment of ATIs in individuals with recurrent tonsillitis from a socio-economic perspective. Further evaluation should assess how differences in uptake and sustained use of homeopathic adjuvant therapy, as well as changing patterns of antibiotic prescribing, impact on cost effectiveness.

Antecedents of Individuals' Concerns Regarding Hospital Hygiene and Surgery Postponement During the COVID-19 Pandemic: Cross-sectional, Web-Based Survey Study.

BACKGROUND: The COVID-19 pandemic poses a major challenge to people's everyday lives. In the context of hospitalization, the pandemic is expected to have a strong influence on affective reactions and preventive behaviors. Research is needed to develop evidence-driven strategies for coping with the challenges of the pandemic. Therefore, this survey study investigates the effects that personality traits, risk-taking behaviors, and anxiety have on medical service-related affective reactions and anticipated behaviors during the COVID-19 pandemic. OBJECTIVE: The aim of this study was to identify key factors that are associated with individuals' concerns about hygiene in hospitals and the postponement of surgeries. METHODS: We conducted a cross-sectional, web-based survey of 929 residents in Germany (women: 792/929, 85.3%; age: mean 35.2 years, SD 12.9 years). Hypotheses were tested by conducting a saturated path analysis. RESULTS: We found that anxiety had a direct effect on people's concerns about safety (ß=-.12, 95% CI -.20 to -.05) and hygiene in hospitals (ß=.16, 95% CI .08 to .23). Risk-taking behaviors and personality traits were not associated with concerns about safety and hygiene in hospitals or anticipated behaviors. CONCLUSIONS: Our findings suggest that distinct interventions and information campaigns are not necessary for individuals with different personality traits or different levels of risk-taking behavior. However, we recommend that health care workers should carefully address anxiety when interacting with patients.

Comparative analysis of resource utilization in integrative anthroposophic and all German pediatric inpatient departments.

BACKGROUND: Integrative Medicine (IM) combines conventional and complementary therapies. It aims to address biological, psychological, social, spiritual and environmental aspects of patients' health. During the past 20 years, the use and request of IM in children and adults has grown. Anthroposophic Medicine (AM) is an IM approach frequently used in children in Germany. From both public health and health economic perspectives, it is relevant to investigate whether there are differences in the resource utilization between integrative pediatric departments (IPD) and the entirety of all pediatric departments. METHODS: Standard ward documentation data from all German integrative anthroposophic pediatric departments (2005-2016; N = 29,956) is investigated and systematically compared to data of the entirety of all pediatric departments in Germany derived from the Institute for the Hospital Reimbursement System (2005-2016, N = 8,645,173). The analyses focus on: length of stay, Diagnosis Related Groups (DRG), Major Diagnosis Categories (MDC), and effective Case Mix Index (CMI). RESULTS: The length of stay in the IPD (M = 5.38 ± 7.31) was significantly shorter than the DRG defined length of stay (M = 5.8 ± 4.71; p < .001; d = - 0.07) and did not exceed or undercut the DRG covered length of stay. Compared to the entirety of all pediatric departments (M = 4.74 ± 6.23) the length of stay was significantly longer in the in the IPD (p <. 001; d = 0.12). The effective CMI in IPD and all pediatric departments were identical (M = 0.76). The frequencies of DRG and MDC differed between IPD and all pediatric departments, with higher frequencies of DRGs and MDCs associated with chronic and severe illnesses in the IPD. CONCLUSIONS: Treatment within integrative anthroposophic pediatric departments fits well in terms of the DRG defined conditions concerning length of stay, even though integrative pediatric patients has an increased length of stay of averagely 1 day, which is most likely associated to time consuming, complex integrative treatment approaches and to a certain extend to higher amount of chronic and severe diseases.

[Motivation for Specialisation in General Practice - A Quantitative Study of NRW's Medical Students in Support of Targeted Recruitment]. / Motivationale Faktoren für die Präferenz der Fachrichtung Allgemeinmedizin ­ eine quantitative Untersuchung unter Medizinstudierenden NRWs für eine zielgerichtete Nachwuchsgewinnung.

AIM OF STUDY: Due to forecasted shortage of general practitioners, we conducted an online survey of all medical students in North-Rhine-Westphalia to identify and quantify determinants in medical students' decision to specialize in general practice (GP). METHODOLOGY: To identify the motives driving the choice of GP as a career, responses of 3976 participants (22.6% of medical students invited) were subjected to factor analysis. Relationships between extracted factors and career choice were ascertained via regression analysis adjusted for population characteristics. All participants who had positioned themselves distinctly for/against GP were included in regression analysis (n=2862). RESULTS: Four of five identified factors were significantly associated with the intended choice of GP. "Comprehensive patient contact" (OR 4.02; 95% CI [3.5-4.6]), and "flexible working hours" (OR 1.35; 95% CI [1.2-1.5]) represent factors associated with choosing GP despite the perception of "superior career opportunities, income and status in other specializations" (OR 1.14; 95% CI [1.0-1.3]). Meanwhile, preference for "specialization, research and teamwork in other disciplines" (OR 0.55; 95% CI [0.5-0.6]) obstructs the intended choice of GP. CONCLUSION: GP recruitment can profit from focused sponsorship of students' interest in patient contact within GP clerkships, appropriate GP teaching structure at the universities, enhanced research and teamwork opportunities, and increased flexibility of working hours.

The prevalence of young carers - a standardised survey amongst school students (KiFam-study).

BACKGROUND: Children and adolescents who provide care, assistance or support for a chronically ill family member are called young carers. While there is a growing body of research about their specific situation, needs and impact of caring, only very few studies provide information on prevalence rates. OBJECTIVES: The aim was to provide prevalence data for young carers in Germany, and to describe and quantify the nature and extent of their help. DESIGN: A cross-sectional study. SETTINGS: Data collection took place between 2016 and 2017 in 44 secondary schools (fifth to 13th grade) in North Rhine-Westphalia, Germany. PARTICIPANTS: A total of 6313 students aged from 10 to 22 years participated in this study. They represent 0.5% of the basic population. METHODS: Based on the results of a preliminary qualitative study, a standardised electronic questionnaire was developed, which comprised four subject areas: socio-demographic information, general daily aids, health-related quality of life and chronic illness within the family. Statistical analyses included chi-square tests for nominal data and univariate analyses of variance for metrical data together with 95% confidence intervals. RESULTS: 19.6% (n = 1238) of all respondents state that someone in their family needs help due to a chronic illness. Nevertheless, not all of them are involved in caring activities. The prevalence of those defined as young carers in this study is 6.1% (n = 383), 64% are girls. They take on a wide range of activities. In addition to domestic work, they help their ill relatives with mobility, dressing and undressing, medication, feeding, personal hygiene and with intimate care. CONCLUSIONS: The data provide a good insight into the situation of young carers. The prevalence rate is higher than expected. It refers to the social relevance of this topic and the need for further investigations.

On the preference for linear regression models in children: Results of a field study in elementary school children.

We aimed at showing that children are able to identify and draw a line of best fit through a cloud of points according to the concept of linear regression. A sample of 72 children in third and fourth primary school grades were given two different tasks. In a first task, 10 different sheets with three illustrations of the same scatterplot with different lines of regression to choose from were presented. In a second task, scatterplots were given and children were asked to draw a line of best fit with pencil and ruler. In the first task bisector regression was preferred (χ2 = 15.21, df = 4, p = .004), whereas in the second conventional regression ordinary least squares (X|Y) was favored (χ2 = 27.14, df = 4, p < .001). In summary, the preference of the traditional regression model using a minimization in the vertical dimension was only partly supported by our data.

Do patients of integrative anthroposophic pediatric inpatient departments differ? Comparative analysis to all pediatric inpatients in Germany considering demographic and clinical characteristics.

BACKGROUND: Integrative medicine (IM) is a patient-centered, evidence-based, therapeutic paradigm which combines conventional and complementary approaches. The use of IM in pediatrics has increased in the past two decades and parents' demand for it is growing. An IM whole systems approach is anthroposophic medicine. Considering the growing demand for integrative approaches in children, it is relevant from a public health perspective to find out which kind of children use IM in Germany and whether they differ from the entirety of pediatric inpatients in Germany. Moreover, it would be interesting to known, whether these patients are willing to travel a longer distance to gain integrative treatment. METHODS: The present study investigates the standard ward documentation datasets of 29,956 patients of all German integrative anthroposophic pediatric inpatient wards from 2005 to 2016 and compares them systematically to collect data of the entirety of all pediatric inpatient wards in Germany. Apart from patients' age and gender, and the ICD-10 admission diagnoses, the geographical catchment area of the hospitals were analyzed. RESULTS: Sociodemographic characteristics of pediatric inpatients in the integrative anthroposophic departments (IAH) did not differ from the entirety of all pediatric inpatients. Regarding clinical characteristics, higher frequencies were found for endocrine, nutritional and metabolic diseases (IAH: 7.24% vs. 2.98%); mental, behavioral, and neurodevelopmental disorders (IAH: 9.83% vs. 3.78%) and nervous diseases (IAH: 8.82% vs. 5.16%) and lower frequencies for general pediatric diseases such as respiratory diseases (IAH: 17.06% vs. 19.83%), digestive diseases (IAH: 3.90% vs. 6.25%), and infectious and parasitic diseases (IAH: 12.88% vs. 14.82%) in comparison to the entirety of all pediatric inpatients in Germany. The IAH showed a broad catchment area, with most patients being from former, Western federal republic of Germany. Large catchment areas (> 100 km) for the IAH are merely covered by severe and chronic diseases. CONCLUSION: Pediatric inpatients of IAH do not differ from the entirety of pediatric inpatients in Germany regarding sociodemographic characteristics but show differences regarding clinical characteristics. Parents are willing to travel further distance to get specialized integrative anthroposophic medical care for children with severe and chronic diseases.

A proof-of-concept trial of HELIOX with different fractions of helium in a human study modeling upper airway obstruction.

BACKGROUND: Helium in oxygen (HELIOX) can relieve airway obstruction and lower the work of breathing because it increases the threshold at which turbulent gas flow is induced. Less turbulent and more laminar flow lowers the work of breathing. According to guidelines, the fraction of Helium in HELIOX should be maximized (e.g. to 79%). Here, we investigate whether HELIOX with less than 60% of Helium is able to relieve the sensation of dyspnea in healthy volunteers. METHODS: 44 volunteers underwent resistive loading breathing different gases (medical air and HELIOX with a fraction of 25%, 50% or 75% helium in oxygen) in a double-blinded crossover design. Subjects rated their degree of dyspnea (primary outcome parameter) and the variability of noninvasively measured systolic blood pressure was assessed. RESULTS: Dyspnea was significantly reduced by HELIOX-containing mixtures with a fraction of helium of 25% or more. Similarly, blood pressure variability was reduced significantly even with helium 25% during respiratory loading with the higher load, whereas with the smaller load an effect could only be obtained with the highest helium fraction of 75%. CONCLUSION: In this clinical trial, HELIOX with less than 60% of helium in oxygen decreased the sensation of dyspnea and blood pressure variability, a surrogate parameter for airway obstruction. Therefore, higher oxygen fractions might be applied without losing the helium-related benefits for the treatment of upper airway obstruction. TRIAL REGISTRATION: Registration with clinical trials (NCT00788788) and EMA (EudraCT number: 2006-005289-37).

Evaluation of the palliative symptom burden score (PSBS) in a specialised palliative care unit of a university medical centre - a longitudinal study.

BACKGROUND: The implementation of standardised, valid and reliable measurements in palliative care is subject to practical and methodological challenges. One aspect of ongoing discussion is the value of systematic proxy-based assessment of symptom burden in palliative care. In 2011, an expert-developed proxy-based instrument for the assessment of symptom burden in palliative patients, the Palliative Symptom Burden Score (PSBS), was implemented at the Specialised Palliative Care Unit of the University Medical Centre in Dusseldorf, Germany. The present study investigated its feasibility, acceptance and psychometric properties. METHODS: The PSBS was rated by nursing staff three times a day over 5 years (N = 820 patients). Feasibility and nurses' acceptance of PSBS were analysed. Structural validity was investigated by principal component analysis. Construct validity was examined via cross-validation with the Hospice and Palliative Care Evaluation checklist. Discriminative validity of the PSBS was analysed by means of Kruskal-Wallis test of patients' performance score. Reliability of the PSBS was evaluated by internal consistency analysis, test-retest and split-half-reliability. Inter-rater reliability was investigated by observer agreement of nurses' ratings of symptom burden within a day. Sensitivity to change was analysed by Wilcoxon test with repeated measures of the PSBS before and after palliative complex treatment. RESULTS: A high degree of acceptance and the feasibility of a high-frequency proxy-based symptom burden assessment approach were demonstrated. There were low rates of missing values and no indications of the adoption of prior ratings. PSBS in its present form demonstrates good structural and construct validity (rs = .27-.79, p's < .001) and high sensitivity to changes in symptom burden (p's < .01, except sweating), but unsatisfactory reliability (α = .41-.67; test-retest: rs = .30-.88; p's < .001; split-half: rs = .69; p < .001; inter-rater: n.s.). CONCLUSIONS: The study presents a framework for the post hoc validation of an already existing documentation tool in palliative care. This study supports the notion that PSBS might not be reflective of an overall construct and will therefore require further development and critical comparison to other already established symptom burden instruments in palliative care.

Use of the Bovine Udder Skin model to evaluate the tolerability of Mesem cosmetic cream.

Observational studies of Mesem cream (based on Mesembryanthemum crystallinum L. plant extract) found that it had positive effects on skin hydration and smoothing of the skin. However, some patients reported skin irritation effects. The current study evaluated the skin tolerability of Mesem cream, as compared to the carrier cream (without the active ingredient), by using the isolated perfused bovine udder skin model. The primary outcomes investigated were cytotoxicity (i.e. cell viability), assessed with the MTT assay, and irritancy and inflammation, assessed by measuring PGE2 tissue levels. A total reaction score was calculated by combining the results for each parameter. In the case of a single topical application, significant differences were found between the carrier cream and the Mesem cream. While the application of carrier cream resulted in low cytotoxicity (-8.4% change in viability, as compared to the untreated control), the Mesem cream was more cytotoxic (-18.7% change). In addition, one hour after application, PGE2 levels were higher in Mesem cream-treated skin, as compared to carrier cream-treated skin (16.6% versus 11.3%). Further experiments (tape-stripped skin and repeated application) also found significant differences between the two creams in the results obtained. Evaluation of the effectiveness, safety and tolerability of phyto-cosmetic products is important. Our results confirmed the findings of two previous human observational studies (the human patch test and open application study). Future experiments to understand the underlying principles of its effectiveness, safety and tolerability should include extracts of M. crystallinum L. juice, as well as the Mesem cream itself.