Joint Statement (DZK, DGRh, DDG) on the Tuberculosis Risk with Treatment Using Novel Non-TNF-Alpha Biologicals.

BACKGROUND: While the risk of tuberculosis (TB) reactivation is adequately documented in relation to TNF-alpha inhibitors (TNFi), the question of what the tuberculosis risk is for newer, non-TNF biologics (non-TNFi) has not been thoroughly addressed. METHODS: We conducted a systematic review of randomized phase 2 and phase 3 studies, and long-term extensions of same, published through March 2019. Of interest was information pertaining to screening and treating of latent tuberculosis (LTBI) in association with the use of 12 particular non-TNFi. Only rituximab was excluded. We searched MEDLINE and the ClinicalTrial.gov database for any and all candidate studies meeting these criteria. RESULTS: 677 citations were retrieved; 127 studies comprising a total of 34,293 patients who received non-TNFi were eligible for evaluation. Only 80 out of the 127 studies, or 63 %, captured active TB (or at least opportunistic diseases) as potential outcomes and 25 TB cases were reported. More than two thirds of publications (86/127, 68 %) mentioned LTBI screening prior to inclusion of study participants in the respective trial, whereas in only 4 studies LTBI screening was explicitly considered redundant. In 21 studies, patients with LTBI were generally excluded from the trials and in 42 out of the 127 trials, or 33 %, latently infected patients were reported to receive preventive therapy (PT) at least 3 weeks prior to non-TNFi treatment. CONCLUSIONS: The lack of information in many non-TNFi studies on the number of patients with LTBI who were either excluded prior to participating or had been offered PT hampers assessment of the actual TB risk when applying the novel biologics. Therefore, in case of insufficient information about drugs or drug classes, the existing recommendations of the German Central Committee against Tuberculosis should be applied in the same way as is done prior to administering TNFi. Well designed, long-term "real world" register studies on TB progression risk in relation to individual substances for IGRA-positive cases without prior or concomitant PT may help to reduce selection bias and to achieve valid conclusions in the future.

[Infection Control Professionals' Views on the Handling of MRSA-Colonised Healthcare Workers]. / Der Umgang mit MRSA bei Beschäftigten im Gesundheitsdienst aus Sicht der Krankenhaushygiene.

Background: Colonisation with methicillin-resistant Staphylococcus aureus (MRSA) is a particular challenge for medical staff and their facilities, with a key role being played by physicians alongside infection control and hospital hygiene professionals. Methods: In 2014, infection control and hygiene staff were surveyed on the handling of hospital staff with MRSA colonisation. The questionnaire queried on MRSA management in hospitals and on the cooperation between hygiene staff and hospital physicians and was compared to a survey of physicians' experience with the care of MRSA-positive hospital staff. Results: 124 hospital hygiene professionals participated in the survey. General screenings of staff members were reported mainly for cases of MRSA outbreak. Temporary colonisation is differentiated from permanent colonisation (47%). 2 unsuccessful attempts at decolonisation are normally regarded as an indicator for a permanent colonisation. Generally there was cooperation between hospital physicians and hygiene staff. The responsibility for screening and decolonisation of staff members is shared by both groups with the groups placing emphasis on different focal points. Different approaches for the handling of MRSA-positive staff were reported and recommendations for the work ability vary from merely observing the standard hygiene regulation to refraining from close patient contact or even complete absence from work. Conclusion: MRSA colonisation in hospital staff is being dealt with in different manners. Infection control and hospital hygiene professionals are equally involved in the treatment. Clear regulations would benefit the handling of MRSA in staff members.

[Current Issues Arising from Tuberculosis Screening with Interferon-Gamma-Release Assays (IGRAs)]. / Aktuelle Fragestellungen zum Tuberkulose-Screening mit Interferon-Gamma-Release Assays (IGRAs).

A positive IGRA test does not always indicate a latent tuberculosis infection (LTBI); the prevalence of LTBI in the tested collective must be carefully considered in test interpretation. When IGRAs are performed repeatedly in healthcare workers (BiG), variabilities of test results (conversions and reversions of the respective previous negative or positive result) can be expected. Therefore only individuals for whom there is an established risk of being infected by Mycobacterium tuberculosis (M.tb.), i.e. significantly prolonged direct exposure to an infectious TB case, should be tested. Positive IGRA results alone do not reliably predict subsequent progression to active TB disease. According to the current body of scientific knowledge, IGRAs are not superior to the tuberculin skin test (TST) in the case of young children.

Comparison of different non-invasive methods for detection of allergic asthma.

Non-invasive methods to assess inflammation of lower airways are induced sputum (IS), exhaled nitric oxide (eNO), and exhaled breath condensate (EBC). Here we focused on the assessment of airway inflammation with a panel of non-invasive methods in health care workers (HCWs) with suspected latex allergy with and without current allergic respiratory symptoms about 10 years after the latex ban in German health care facilities. Seventy-seven non-smoking subjects were examined by skin prick test and specific IgE measurements, eNO, IS, and EBC. Sensitivity, specificity, and positive and negative predicted values for relevant biomarkers were calculated using current asthma symptoms as the gold standard. Twenty-nine subjects (38%) reported ongoing asthmatic symptoms (AS). In these subjects the EBC concentrations of nitrogen oxides (NO(x); p=0.027) and leukotriene B(4) (p=0.025) were significantly higher than in subjects without AS. In addition, in the subjects with AS the numbers of eosinophils (p=0.015) and the concentrations of IL-5 (p= 0.021) in IS samples were significantly higher than in the subjects without AS. A good correlation between several inflammatory markers in IS was detected. The maximum Youden Index was reached for IS total eosinophils ≥3.5·10(4) with a test efficiency of 0.72. In conclusion, non-invasive inflammatory monitoring with EBC and IS may assist the diagnosis of allergic asthma. Self-reported current asthmatic symptoms were reflected by eosinophilic inflammation and the best parameter to support the asthma diagnosis is a total number of eosinophils ≥3.5·10(4) in IS.

Enhanced cost-benefit analysis of strategies for LTBI screening and INH chemoprevention in Germany.

OBJECTIVES: There is only limited economic data in head-to head comparison between a whole blood QuantiFERON TB Gold in tube (QFT) and the tuberculin skin test (TST) when screening and treating for latent tuberculosis infection (LTBI), and no published study to date that takes into account the predictive value of the two tests. METHODS: Health and economic outcomes of isoniazid preventive treatment (IPT) of close contacts were compared in a decision tree model to perform a cost-benefit analysis with respect to isoniazid related hepatotoxicity and early post-exposure TB over a 2-y period, using the QFT or TST alone or QFT as a confirmatory test for TST results. RESULTS: Cost of screening and treating for using the QFT alone amounted to euro215.79 per close contact, less than that of dual step-testing (euro227.89) or using TST alone (euro232.58). Savings amounted to euro12,200 or euro16,791 per 1000 close contacts, respectively. QFT based procedures were most sensitive to low compliance with IPT or increasing price. Costs of dual step screening was mostly influenced by cost of treating TB disease. When the progression rate for QFT was lowered to that for the TST in a sensitivity analysis, the relationship between the strategies remained robust. In addition, costs of the QFT strategy decreased to euro165.1, and those of the dual step strategy to euro218.4. CONCLUSION: IPT on the basis of using the QFT assay alone produces less cost and reduces more TB cases than other strategies in a low-incidence setting. These data have implications for the rational implementation of screening strategies in contact investigation.

[Unspecific back pain - basic principles and possibilities for intervention from a psychological point of view]. / Unspezifische Rückenschmerzen - Grundlagen und Interventionsmöglichkeiten aus psychologischer Sicht.

INTRODUCTION: Back pain is one of the most common and expensive health problems in Germany. Apart from somatic parameters, psychological factors are thought to influence the aetiology and, especially, the chronification of back pain. A literature search has been performed to establish which psychological procedures are used in the diagnosis, prevention and therapy for back pain, and how effective they are. METHOD: The connection between back pain and psychological factors was investigated in English and German technical articles identified in a literature search in Medline (2000-2006) and in psyndex (2000-2006). 714 hits were identified for the key words "back pain and prevention", 61 hits for "back pain and psychological factors", 732 hits for "back pain and risk factors" and 4 hits for "back pain and chronification of pain". 75 technical articles or studies were selected from these hits and used as a basis for the evaluation of the above questions. The search was completed by a manual search in the literature lists of published articles, perusing monographs, searching the internet and evaluating congress and meeting reports (2000-2008). RESULTS: The results of various studies show that cognitive, emotional and behavioural aspects and the processes of respondent and operant learning are of great importance in processing and overcoming pain. Biopsychosocial procedures appear to be superior to biomedical procedures. There has been good research on the (psychological) risk factors which contribute to the chronification of pain. It seems to be sensible to use screening procedures, such as the "Orebro Musculoskeletal Pain Questionnaire (OMPQ)" for the identification of patients at increased risk of chronification. For patients with chronic symptoms, there are evidence-based psychological programme components; these are usually successful, especially as part of multimodal programmes. As yet, there have only been initial studies on the use of psychological intervention for prevention, particularly in occupational settings. DISCUSSION: In the high risk group of patients already suffering from back pain, relapses and chronification can best be prevented by multimodal programmes. A decisive condition for the success of these physiotherapeutic, ergotherapeutic, sports therapeutic and psychotherapeutic interventions is apparently that there should be a standardised procedure in accordance with the theoretical principles of behavioural therapy, complied with by all those involved in the process. However, the principle objective of all measures should be the avoidance of the transition from acute to chronic back pain and the protracted and expensive clinical course this can lead to. Psychological intervention appears to work here as well. Further studies are needed to clarify whether the psychological program components are effective in isolation or whether they must be embedded in a multimodal (preventive) concept. It must also be investigated which target groups benefit most from which type of preventive (psychological) intervention. Provision of specific information is an alternative preventive approach. This health psychological or educative procedure corresponds to demedicalisation of this condition. Although media campaigns have been successfully performed in Australia, it is as yet unclear whether these can be transferred to Germany and which structural changes these would require in our health care system.

Prevention of occupational skin disease: a workplace intervention study in geriatric nurses.

BACKGROUND: Health care workers have an increased risk of occupational dermatosis. OBJECTIVES: To determine whether a skin care programme reduces skin disease on the hands of geriatric nurses and increases protective behaviour and the provision of skin care products at the workplace. The intervention was based on a 2-h skin care training session and an occupational advisory service. METHODS: The study design was a randomized intervention study with a control group. Three hundred and eighty-eight geriatric nurses were included in the intervention group exposed to a skin care programme (IG; n = 146) and in the control group (CG; n = 242). Both groups completed questionnaires on exposure and underwent clinical examinations of their hands at the beginning and after a 12-month period. Preventive measures initiated by the employer at the workplace were documented at baseline and at 3 months after the intervention. RESULTS: At baseline, no difference between the IG and the CG was found with respect to skin changes or work-related behaviour. At follow-up, the frequency of skin disease was significantly reduced in the IG, from 26% at baseline to 17% at follow-up, whereas the frequency remained almost unchanged in the CG. Effects on behaviour in the IG included significant increases in the use of moisturizers and hand disinfection instead of hand washing. The provision of cotton gloves and barrier cream products increased at intervention workplaces. CONCLUSIONS: Effective implementation of an occupational skin care programme for geriatric nurses should include both the training of the nurses and an occupational advisory service for management.

[Health indicators and preventive behaviour of older employees in geriatric care]. / Gesundheitsindikatoren und Präventionsverhalten bei älteren Beschäftigten in der Altenpflege.

STUDY OBJECTIVE: As a consequence of the demographic transition, the proportion of geriatric nurses aged over 50 is increasing. The present study examines whether the prevalence of skin and back diseases and preventive behaviour differ between this group and younger employees. An additional objective was to record the proportion of older employees with a health- and occupation-related impairment. METHODS: 2 149 nurses working in home care settings and nursing homes were questioned in written form about their working ability, their preventive behaviour and their health situation. They were also subjected to dermatological investigation (with the Osnabrück Hand Eczema Severity Index - OHSI) and orthopaedic investigation (based on the multiple-step inventory of examinations). RESULTS: Older nurses more often rated their working ability as "(fairly) poor" than did younger nurses. This applied both to physical demands (11 vs. 4%) and to psychological demands (10 vs. 5%). They were also more affected by symptoms in the cervical spine (28 vs. 13%) and the lumbar spine (56 vs. 37%). Hand eczema was not more prevalent in older nurses. The state of health of 10% of the nurses aged over 50 indicated a health- and occupation-related impairment in regard to work ability and back complaints. Roughly equal proportions of the younger and older groups participated in measures for the primary prevention of back symptoms. The older nurses participated more often in advisory sessions on skin protection and more frequently applied cream to their hands. The younger nurses were in skin contact with water or fluids for shorter periods and more often exclusively used disinfectants after patient contact. CONCLUSION: Geriatric nurses with a health- and occupation-related impairment require intensive measures to support their health and to prevent health damage and to stop them from leaving work prematurely. If at all possible, these measures should not be restricted to a single social insurance agency. The individual preventive behaviour to avoid occupational back symptoms is not dependent on age. An age effect was observed for individual measures to protect the skin. Nevertheless, these had no effect on the risk of disease. The results indicate that more attention should be given to older employees during occupational training.

Cost-optimisation of screening for latent tuberculosis in close contacts.

The aim of the present study was to perform cost-minimisation analysis of contact investigation from a public health perspective using the tuberculin skin test (TST) and a new blood assay, QuantiFERON-TB Gold (QFT-G). A decision-analysis model simulated the costs of investigating a cohort of adult close tuberculosis contacts by the public health service following the current German guidelines over a period of 2 yrs. The economic outcomes were compared with alternative screening strategies. These were: 1) QFT-G instead of TST; 2) TST followed by QFT-G; and 3) TST followed by QFT-G in vaccinated (bacille Calmette-Guérin (BCG)) subjects. In a base-case analysis, the costs of TST-based screening were 91.06 Euros (EUR).contact(-1), assuming a 1% tuberculosis-case-finding incidence. The least expensive strategy was TST screening plus subsequent QFT-G testing (52.05 EUR), resulting in a 43% cost reduction. Using QFT-G alone in BCG-vaccinated subjects who tested positive in the TST led to a 39% cost reduction. The savings using QFT-G alone instead of TST amounted to 29.77 EUR.contact(-1). The results depended on the acquisition costs assumed and the proportion of positive results in TST-based screening. Screening for tuberculosis by combining tuberculin skin testing and QuantiFERON-TB Gold markedly reduces public health costs compared with tuberculin skin test screening alone.

Cost-effectiveness of isoniazid chemoprevention in close contacts.

The aim of the present study was to perform a cost-effectiveness analysis in young and middle-aged adults with latent tuberculosis (TB) infection in Germany. A Markov model simulated the progression of 20- and 40-yr-old close contacts of active TB cases over 20 yrs. Health and economic outcomes of isoniazid (INH) chemoprevention versus no intervention were compared. The analysis determined the incremental cost-effectiveness ratio in terms of cost per quality-adjusted life year and the difference between numbers of TB cases and of TB-related deaths. INH chemoprevention prevented 79% of expected TB cases in both age groups, and saved 9,482 and 9,142 in the lower and higher age groups, respectively, per case prevented. Quality-adjusted life expectancy was slightly extended by 8 days in the lower age group and 7 days in the higher age group, at a cost saving of 417 and 375, respectively, per person. Annual savings were 20,862 and 18,742 per 1,000 contacts, respectively. The number needed to be treated to prevent one TB case in the lower age group was 23 and 25 in the higher age group. The programme also prevented three TB-related deaths in the younger and two in the older cohort. The results are highly sensitive to treatment-cost assumptions. In conclusion, isoniazid chemoprevention in Germany is a highly cost-effective approach for reducing the burden of tuberculosis in recently converted young and middle-aged adults.

Psychosocial work factors and dementia.

AIMS: To evaluate the association between psychosocial workplace factors and dementia in a case-control study. METHODS: Patients with dementia (aged 55-99 years) were recruited from 23 general practices in the city of Frankfurt-on-Main and surrounding area in 1998-2000. Of these, 108 were suffering from possible Alzheimer's disease, 59 from possible vascular dementia, and 28 from secondary or unclassified dementia. A total of 229 control subjects (aged 60-94 years) was recruited from the same study region: 122 population controls and 107 dementia-free ambulatory patients. A detailed job history was elicited in a structured personal interview (next-of-kin interviews of cases). Psychosocial work exposure was assigned to cases and control subjects by linking lifetime job histories with a Finnish job-exposure matrix. Data were analysed using logistic regression, to control for age, region, sex, dementia in parents, education, smoking, and the psychosocial network at age 30. RESULTS: There were decreased odds ratios for high challenge at work, high control possibilities at work, and high social demands at work. High risks for error at work revealed a significant positive association with the diagnosis of dementia. Restriction of the analysis to cases with possible Alzheimer's disease or to cases with possible vascular dementia led to similar results. CONCLUSIONS: These results support a role for psychosocial work factors in the aetiology of dementia. As an alternative explanation, people might have chosen jobs with poor work factors due to preclinical dementia, which becomes clinically manifest decades later.

Epidemiology of acne in the general population: the risk of smoking.

BACKGROUND: Acne is a common skin disorder, but epidemiological data from the general population obtained by examination are scarce. Clinical experience suggests an association between smoking and acne, although confirmatory evidence from appropriate studies is lacking. OBJECTIVES: To determine the prevalence and demographic factors of acne in a general population sample and to investigate the association of smoking and acne on a qualitative and quantitative level. METHODS: In a cross-sectional study, 896 citizens (aged 1--87 years, median 42) of the City of Hamburg were dermatologically examined. The prevalence and severity of acne were recorded and further information on demographic variables, medical history, and alcohol and cigarette consumption were obtained by a standardized interview. RESULTS: According to the clinical examination, acne was present in 26.8% overall, and was more prevalent in men (29.9%) than women (23.7%) (odds ratio, OR 1.37, 95% confidence interval, CI 1.01--1.87). Prevalence followed a significant linear trend over age with peak prevalence between 14 and 29 years (P < 0.001). The reported age at onset was significantly lower in women than men (P = 0.015). According to multiple logistic regression analyses acne prevalence was significantly higher in active smokers (40.8%, OR 2.04, 95% CI 1.40--2.99) as compared with non-smokers (25.2%). A significant linear relationship between acne prevalence and number of cigarettes smoked daily was obtained (trend test: P < 0.0001). In addition, a significant dose-dependent relationship between acne severity and daily cigarette consumption was shown by linear regression analysis (P = 0.001). CONCLUSIONS: Smoking is a clinically important contributory factor to acne prevalence and severity.

A straightforward approach to isolate DNA sequences with potential linkage to the retinoblastoma locus.

From a human-Chinese hamster somatic cell hybrid a clone was derived containing chromosome 13 in duplicate as its only human material. This clone was used to construct a human chromosome 13-specific recombinant DNA-library. Overlapping Sau3AI DNA sequences (11.9-17.2 kb) from the cell hybrid were inserted into the lambda phage vector EMBL4. From eleven recombinants having a human insert thirteen putative unique DNA sequences were isolated and cloned into the plasmid vector pBR329. A human-mouse hybrid containing a human chromosome 13 with a deletion of 13q14 and lacking its undeleted homologue was constructed to be used in a selection procedure for DNA sequences belonging to band q14. Three probes originating from two different phages were assigned to 13q14 because they did not hybridise to DNA from this cell hybrid. One of these 13q14 probes detects a low frequency (2/44) MspI restriction fragment length polymorphism. The probes are now being used for screening a cosmid library to find adjacent polymorphic sequences with a RFLP information content suitable for application in the diagnosis of hereditary retinoblastoma.

Covalent protein binding of reactive adriamycin metabolites in rat liver and rat heart microsomes.

Covalent binding of 3H-labeled adriamycin metabolites to bovine serum albumin and microsomal protein is demonstrated in an aerobic incubation system with rat liver and rat heart microsomes, respectively, using exhaustive organic solvent extraction and gel chromatography. Covalent protein binding was dependent on active microsomes, NADPH, and oxygen and was inhibited by reduced glutathione and other sulfhydryl compounds. The anthracycline moiety was spectrophotometrically evidenced in the adriamycin metabolite(s) covalently bound to protein. Thus, enzymatic activation of adriamycin in the heart with consecutive covalent protein binding of reactive adriamycin semiquinone radicals may contribute to adriamycin cardiotoxicity.

Time and cell systems as variables in fusion experiments with polyethylene glycol.

Cell hybridization was done between a monolayer of B14-150 Chinese hamster cells and a suspension of either mouse leukemia cells or normal human lymphocytes. Cell contact was obtained by centrifugation of the suspension cells onto the monolayer cells in a culture plate. Cell fusion was done by means of polyethylene glycol (PEG). The optimum time for PEG exposure as well as the yield of hybrid cells differed markedly with the different combinations.