Wolfgang Uter

Frequency of Malnutrition in Older Adults: A Multinational Perspective Using the Mini Nutritional Assessment

OBJECTIVES: To provide pooled data on the prevalence of malnutrition in elderly people as evaluated using the Mini Nutritional Assessment (MNA).

European Society of Contact Dermatitis guideline for diagnostic patch testing – recommendations on best practice

The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed‐type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.

National rates and regional differences in sensitization to allergens of the standard series-Population-adjusted frequencies of sensitization (PAFS) in 40,000 patients from a multicenter study (IVDK)

Sensitization rates to contact allergens vary between centers and are influenced by sex and age. Eliminating the latter 2 factors by standardization of data by age and sex, the present analysis address possible differences between centers remaining after elimination of these confounders, and analyzes other factors which might influence rates, e.g. the MOAHL index. Overall standardized rates were well within the range reported in previous studies and may be regarded as representing the rates of the “patch test population” in Central Europe (e.g. nickel sulfate 12.9%, fragrance mix 10.5″. balsam of Peru 7.3%. thimerosal 5.6%). For this analysis, data of those departments which contributed more than 2000 patients or of those with extreme proportion concerning sex, age and occupational cases were selected. Patients from these 10 departments differed considerably will regard to the items of the MOAHL index and with regard to standardized rates. The items of the MOAHL index proved to be suitable for describing different patch test populations and for explaining some differences between centers. Only ‘atopic dermatitis’ seems to have little influence on (standardized) rates. Face dermatitis is not yet represented in the MOAHL index, but should be included, together with age > 40 years, in an extended index (acronym: MOAHLFA). Regional allergen exposure (with striking differences between East Germany, West Germany and to a lesser extent Austria) seems to have a great influence on the sensitization pattern observed in a department. In addition, sociological factors may influence sensitization rates, which is exemplified by high rates of nickel allergy in a socially delined subgroup. Future studies should focus on these factors, as well as on factors concerning patch test practices and quality control.

5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial

BACKGROUND In a phase 3, randomised, non-inferiority trial, accelerated partial breast irradiation (APBI) for patients with stage 0, I, and IIA breast cancer who underwent breast-conserving treatment was compared with whole-breast irradiation. Here, we present 5-year follow-up results. METHODS We did a phase 3, randomised, non-inferiority trial at 16 hospitals and medical centres in seven European countries. 1184 patients with low-risk invasive and ductal carcinoma in situ treated with breast-conserving surgery were centrally randomised to either whole-breast irradiation or APBI using multicatheter brachytherapy. The primary endpoint was local recurrence. Analysis was done according to treatment received. This trial is registered with ClinicalTrials.gov, number NCT00402519. FINDINGS Between April 20, 2004, and July 30, 2009, 551 patients had whole-breast irradiation with tumour-bed boost and 633 patients received APBI using interstitial multicatheter brachytherapy. At 5-year follow-up, nine patients treated with APBI and five patients receiving whole-breast irradiation had a local recurrence; the cumulative incidence of local recurrence was 1.44% (95% CI 0.51-2.38) with APBI and 0.92% (0.12-1.73) with whole-breast irradiation (difference 0.52%, 95% CI -0.72 to 1.75; p=0.42). No grade 4 late side-effects were reported. The 5-year risk of grade 2-3 late side-effects to the skin was 3.2% with APBI versus 5.7% with whole-breast irradiation (p=0.08), and 5-year risk of grade 2-3 subcutaneous tissue late side-effects was 7.6% versus 6.3% (p=0.53). The risk of severe (grade 3) fibrosis at 5 years was 0.2% with whole-breast irradiation and 0% with APBI (p=0.46). INTERPRETATION The difference between treatments was below the relevance margin of 3 percentage points. Therefore, adjuvant APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to 5-year local control, disease-free survival, and overall survival. FUNDING German Cancer Aid.

In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn's disease

As antibodies to tumor necrosis factor (TNF) suppress immune responses in Crohns disease by binding to membrane-bound TNF (mTNF), we created a fluorescent antibody for molecular mTNF imaging in this disease. Topical antibody administration in 25 patients with Crohns disease led to detection of intestinal mTNF+ immune cells during confocal laser endomicroscopy. Patients with high numbers of mTNF+ cells showed significantly higher short-term response rates (92%) at week 12 upon subsequent anti-TNF therapy as compared to patients with low amounts of mTNF+ cells (15%). This clinical response in the former patients was sustained over a follow-up period of 1 year and was associated with mucosal healing observed in follow-up endoscopy. These data indicate that molecular imaging with fluorescent antibodies has the potential to predict therapeutic responses to biological treatment and can be used for personalized medicine in Crohns disease and autoimmune or inflammatory disorders.

Sensitization to 26 fragrances to be labelled according to current European regulation. Results of the IVDK and review of the literature.

To study the frequency of sensitization to 26 fragrances to be labelled according to current European regulation. During 4 periods of 6 months, from 1 January 2003 to 31 December 2004, 26 fragrances were patch tested additionally to the standard series in a total of 21 325 patients; the number of patients tested with each of the fragrances ranged from 1658 to 4238. Hydroxymethylpentylcyclohexene carboxaldehyde (HMPCC) was tested throughout all periods. The following frequencies of sensitization (rates in %, standardized for sex and age) were observed: tree moss (2.4%), HMPCC (2.3), oak moss (2.0), hydroxycitronellal (1.3), isoeugenol (1.1), cinnamic aldehyde (1.0), farnesol (0.9), cinnamic alcohol (0.6), citral (0.6), citronellol (0.5), geraniol (0.4), eugenol (0.4), coumarin (0.4), lilial (0.3), amyl‐cinnamic alcohol (0.3), benzyl cinnamate (0.3), benzyl alcohol (0.3), linalool (0.2), methylheptin carbonate (0.2), amyl‐cinnamic aldehyde (0.1), hexyl‐cinnamic aldehyde (0.1), limonene (0.1), benzyl salicylate (0.1), γ‐methylionon (0.1), benzyl benzoate (0.0), anisyl alcohol (0.0). 1) Substances with higher sensitization frequencies were characterized by a considerable number of ‘++/+++’ reactions. 2) Substances with low sensitization frequencies were characterized by a high number of doubtful/irritant and a low number of stronger (++/+++) reactions. 3) There are obviously fragrances among the 26 which are, with regard to contact allergy, of great, others of minor, and some of no importance at all.

Epidemiology of contact allergy: an estimation of morbidity employing the clinical epidemiology and drug-utilization research (CE-DUR) approach.

Clinical epidemiology (CE) is considered unable to estimate morbidity concerning either contact sensitization (CS) or allergic contact dermatitis (ACD) at the population level. Drug‐utilization research (DUR) methods estimate the morbidity of suitable diseases based on prescription data for disease‐specific drugs. Our objective was to estimate population figures for incidence and prevalence of ACD and CS based on sales data for patch test material in Germany and on patient data from the Information Network of Departments of Dermatology (IVDK). Approximately 600,000 standard series are sold per year in Germany, according to the 2 main manufacterers. This raw sales figure was corrected for certain effects (discarded preparations, proportion of formerly patch‐tested patients, proportion of patients with ACD seeking medical advice) to obtain an estimate of the denominator of patients eligible for patch testing annually, and combined with patch test results from the Information Network of Departments of Dermatology (IVDK). In 17.8% (of 9,266 IVDK patients) ACD was established. Extrapolated to the general population, an incidence of ACD of between 1.7 and 7 per 1000 per year was estimated, depending on whether conservative or more liberal assumptions concerning the above effects were made. Of 78,067 IVDK patients tested between 1992 and 2000, 46.8% had at least 1 positive reaction (+ to + + +), and 22.7% had at least 1 stronger positive reaction (+ + or + + +).The 9‐year prevalence of CS was estimated to lie between 4.0% and 16.6% for the first outcome, and between 2.0% and 8.1% for the second. Concerning single allergens, 1.9–4.5 million individuals are probably sensitized to nickel, and 1.4–3.4 million to fragrance mix among the German population of 82 million inhabitants. The morbidity data found in this study are in good accordance with data from population‐based epidemiological studies. In comparison to these, the CE‐DUR approach seems to be an economically feasible method to estimate continuously the population impact of ACD and CS.

Guidelines for the descriptive presentation and statistical analysis of contact allergy data

The present guidelines aim to support clinical researchers in adequately presenting data on contact allergy, and to use statistical tests appropriate for their data. A description of the mode of selection of patients, and of their relevant demographic details, is an essential prerequisite for the correct interpretation of study results. Proportions and rates, if regarded as estimate of these parameters of a target populations, should normally be supplemented with confidence intervals to address precision. Concordance, i.e., agreement between two ratings in a dependent sample, must be quantified with a chance‐corrected measure such as Cohens kappa coefficient. If the diagnostic quality of an outcome is being assessed, standard measures like sensitivity and specificity, as well as the prevalence‐dependent positive and negative predictive values should be calculated. Often, contact allergy to a certain substance depends on several factors. In this situation, depending on the research question, techniques like stratification, standardization or multifactorial analysis should be employed. With increasing complexity of statistical description and analysis, consulting with a biostatistician is often mandatory.

Contact allergy to fragrances: frequencies of sensitization from 1996 to 2002. Results of the IVDK

Increasing frequencies of sensitization to the fragrance mix (FM) have been acknowledged as a serious problem for many years. It is well known that the single compounds (SCs) of the FM contribute differently to the FM patch rest reactions. In this study, we were interested in the time trends of the FM, the SCs, Myroxylon pereirae resin (MP; balsam of Peru) and oil of turpentine (OT) as possible further indicators of perfume allergy and analysed the data collected by the Information Network of Departments of Dermatology multicentre project from 1996 to 2002. During the study period (1996–2002), the FM [8% petrolatum (pet.)], MP (25% pet.) and OT (1% pet.) were tested in 59 298, 59 334 and 59 478 patients, respectively. SCs were tested in a selected group of patients, ranging from n = 1083 to n = 1924 per year. A significant increase in the proportions of patients with positive reactions to FM, MP and OT between 1996 and 1998 is noted, and a significant decline from 1999 to 2002 (Cochrane Armitage trend test, P < 0.0001). The highest frequency of sensitization to the FM was 13.1% in 1999, and the lowest 7.8% in 2002. The number of concomitant reactions to OT, a surrogate marker for terpenes, in FM‐positive patients was significantly increased between 1997 and 1999. Reactions to SCs in FM‐positive patients were observed in 29.9% (oak moss absolute) to 5.9% (geraniol). There was no time trend in reactions to SCs, although the relative share was increased for isoeugenol, cinnamic aldehyde and geraniol in 1999. In summary, we report for the first time, a significant decline in sensitization to the FM, very probably due to a reduced exposure (less potent allergens used in fine fragrances, possibly less use of natural ingredient‐based cosmetics and lowered use concentration of important fragrance allergens). The differences in ranking of SCs could stimulate (a) a redefinition of the FM and (b) a differentiated preventive and regulatory approach, with oak moss and isoeugenol being regulated strictly by prohibition, concentration limits further reconsidered and/or health warnings and clearly less noxious substances like geraniol treated less restrictively.

The European baseline series in 10 European Countries, 2005/2006 : results of the European Surveillance System on Contact Allergies (ESSCA)

Background: Continual surveillance based on patch test results has proved useful for the identification of contact allergy.