Use of a job exposure matrix to predict the risk of work disability in individuals with back pain: An inception cohort study.

BACKGROUND: Low back pain has a high economic burden in Germany due to back pain-related sick leave, disability pensions, and health care utilization. Work-related factors can predict disabling back pain. Job exposure matrices can be used to consider job demands and occupational characteristics in routine data analysis. OBJECTIVE: This longitudinal analysis tested whether rehabilitation utilization due to musculoskeletal disorders is associated with occupation-linked job exposures in employees with back pain. METHODS: Data from a German cohort study were used, including employees aged 45 to 59 years with self-reported back pain in the last three months. Individuals' job titles were assessed in the baseline survey in 2017 and matched with parameters of aggregated job exposure indices. Administrative data from the German Pension Insurance were used to extract information on rehabilitation utilization. Proportional hazard models tested the associations. RESULTS: We considered data of 6,569 participants (mean age: 52.3 years; 57.7% women). During follow-up, with a maximum of 21 months, 296 individuals (4.5%) utilized medical rehabilitation due to musculoskeletal disorders. Adjusted analyses showed that high physical (HR = 2.87; 95% CI 1.74; 4.75) and overall (HR = 2.34; 95% CI 1.44; 3.80) job exposures were associated with a higher risk of rehabilitation utilization. CONCLUSION: Individuals with back pain working in occupations with high physical job exposures have a higher risk for rehabilitation utilization. To prevent work disability in individuals with back pain, occupational groups with high physical job exposures should be actively informed about tailored intervention options.

Contextual factors in persistent severe back pain: A longitudinal analysis among German employees.

BACKGROUND: Chronic back pain in employees compromises participation in social and daily activities, as well as work. OBJECTIVES: To examine the severity of back pain after 2 years and identify factors predicting stagnation at this level of pain. METHODS: Data were derived from a prospective cohort study with randomized sampling of insurants in the German Pension Insurance using a questionnaire at baseline and follow-up after 2 years. The sample consisted of middle-aged employees (45-59 years) with strong limitations due to back pain (Chronic Pain Grade III or IV), who had not applied for disability pension and did not use medical rehabilitation in the previous 4 years before baseline. Stepwise multivariable logistic regression models with backwards selection were used to identify relevant contextual factors in the stagnation of severe back pain. RESULTS: Of 1208 persons with severe back pain at baseline, 48% had stagnated at that pain level after 2 years. Predictors of persistent severe back pain were older age, poorer general health, more additional disabling conditions, more depressive symptoms, caregiving burden, less pain-related self-efficacy and more fear avoidance beliefs. CONCLUSIONS: In a high-risk subgroup with several co-existing conditions, this analysis highlights (mental) health, social and personal (contextual) factors associated with long-term unfavourable back pain progression. SIGNIFICANCE: Back pain is a condition that often has a chronic or recurrent course, threatening participation in many areas of life. In this study it was found that the unfavourable condition of severe back pain can remain stable for long periods of time in a significant proportion of sufferers. Contextual factors (self-efficacy, fear-avoidance beliefs, caregiving burden) as well as additional health problems should be considered when identifying persons with stagnating pain courses.

Allergen-specific immunotherapy and evidence: A European regulatory perspective.

Allergen immunotherapy (AIT) has been performed for 112 years. In this article we summarize regulatory standards and challenges based on scientific evidence on AIT. Most crucial and timely aspects concerning AIT are addressed from the regulatory perspective of the authors as employees of a national competent authority in Europe: (1) product specificity; (2) clinical efficacy; (3) treatment for adults and children (needs for extrapolation); (4) allergen exposure chambers; (5) biomarkers; (6) standardization; (7) real-world evidence; (8) independent official batch release (benefit and challenges); (9) harmonization on the EU level. The Paul-Ehrlich-Institut (PEI), the Federal Institute for Vaccines and Biomedicines, in Langen near Frankfurt/Main in Germany, examines and evaluates the benefits and risks of AIT products within the course of clinical development, marketing authorization, and subsequently throughout their entire life cycle to ensure high-quality, safe, and effective AIT products.

Rare neurovascular genetic and imaging markers across neurodegenerative diseases.

INTRODUCTION: Cerebral small vessel disease (SVD) is common in patients with cognitive impairment and neurodegenerative diseases such as Alzheimer's and Parkinson's. This study investigated the burden of magnetic resonance imaging (MRI)-based markers of SVD in patients with neurodegenerative diseases as a function of rare genetic variant carrier status. METHODS: The Ontario Neurodegenerative Disease Research Initiative study included 520 participants, recruited from 14 tertiary care centers, diagnosed with various neurodegenerative diseases and determined the carrier status of rare non-synonymous variants in five genes (ABCC6, COL4A1/COL4A2, NOTCH3/HTRA1). RESULTS: NOTCH3/HTRA1 were found to significantly influence SVD neuroimaging outcomes; however, the mechanisms by which these variants contribute to disease progression or worsen clinical correlates are not yet understood. DISCUSSION: Further studies are needed to develop genetic and imaging neurovascular markers to enhance our understanding of their potential contribution to neurodegenerative diseases.

Comparison of allergen immunotherapy practice patterns in inhalant allergies in the United States of America and Europe: Similarities and differences 2023.

IgE-mediated atopic diseases such as allergic rhinitis and rhinoconjunctivitis are common chronic diseases in the western world. Allergen immunotherapy (AIT) plays a fundamental role in the treatment of allergic patients by modulating the underlying immune mechanisms. Though this treatment is integrated in practice-patterns globally, many differences are found in the application of AIT on the national or international level due to heterogeneous methods, and clinical recommendations are given in different parts of the world. This review from authors in Europe and the United States highlights differences and similarities in important aspects of AIT application in the 2 global regions. First, the regulatory situation differs regarding marketing authorization and licensing. Secondly, differences are elaborated in manufacturing practices, marketing distribution and formulations of AIT products. Thirdly, clinical administration patterns in the current guidelines show similarities in indications and contraindications of AIT, but also are divergent in some practical aspects. Informing the readership on similarities, as well as differences of standards in AIT in the United States and Europe, the authors highlight the unmet need of thorough harmonization of standards of AIT, as it is the only disease modifying treatment option available for patients with allergic rhinitis and rhinoconjunctivitis.

Introduction of General Chapters on standard methods for allergen quantification in the European Pharmacopoeia.

The Biological Standardization Project BSP090 has been successfully concluded in 2021. As a result, two standard methods for quantification of the major allergens Bet v 1 and Phl p 5 will be implemented in the European Pharmacopoeia (Ph. Eur.). The General Chapter describing the protocol of the respective Bet v 1-specific ELISA has already been adopted by the Ph. Eur. Commission and will become an official part of the Ph. Eur. in the beginning of 2023. As this will be the first allergen-specific standard method in the EU, this paper intends to summarize the preceding process and outline the measures necessary to comply with the new regulatory requirement.

SARS-CoV-2 and other respiratory pathogens are detected in continuous air samples from congregate settings.

Two years after the emergence of SARS-CoV-2, there is still a need for better ways to assess the risk of transmission in congregate spaces. We deployed active air samplers to monitor the presence of SARS-CoV-2 in real-world settings across communities in the Upper Midwestern states of Wisconsin and Minnesota. Over 29 weeks, we collected 527 air samples from 15 congregate settings. We detected 106 samples that were positive for SARS-CoV-2 viral RNA, demonstrating that SARS-CoV-2 can be detected in continuous air samples collected from a variety of real-world settings. We expanded the utility of air surveillance to test for 40 other respiratory pathogens. Surveillance data revealed differences in timing and location of SARS-CoV-2 and influenza A virus detection. In addition, we obtained SARS-CoV-2 genome sequences from air samples to identify variant lineages. Collectively, this shows air sampling is a scalable, high throughput surveillance tool that could be used in conjunction with other methods for detecting respiratory pathogens in congregate settings.

Work ability score as predictor of rehabilitation, disability pensions and death? A German cohort study among employees with back pain.

BACKGROUND: Sickness absence, disability pensions, and use of healthcare due to disabling back pain are a high economic burden in Germany. Assessment are needed to identify employees who are likely to need intensive support. OBJECTIVE: The cohort study examined whether rehabilitation, disability pensions and death can be predicted by a simple self-reported rating of work ability in employees with back pain in Germany. METHODS: Employees aged 45 to 59 years who reported back pain in the last 3 months completed the Work Ability Score in 2017 (0-10 points). Individual scores were categorized into poor (0-5 points), moderate (6-7) and at least good (8-10) work ability. Outcomes were extracted from administrative records covering the period until the end of 2018. Proportional hazard models were fitted to determine the prognostic benefit of the Work Ability Score. RESULTS: Data for 6,917 participants were included (57.8% women). The median follow-up time was 20 months. Of the participants, 52.1% had a good or excellent, 27.7% a moderate, and 20.2% a poor Work Ability Score. During follow-up, 548 persons were granted rehabilitation measures, 57 persons disability pensions, and 23 died. Fully adjusted analyses showed an increased risk of a rehabilitation measure (hazard ratio = 2.65; 95% CI 2.11; 3.34) and a disability pension (HR = 4.12; 95% CI 2.02; 8.39) in employees with poor work ability. A premature death was not associated with poor work ability. CONCLUSIONS: The Work Ability Score is a potential tool to identify individuals, reporting back pain, with an increased risk of health-related early retirement and work disability.

SARS-CoV-2 and other respiratory pathogens are detected in continuous air samples from congregate settings.

Two years after the emergence of SARS-CoV-2, there is still a need for better ways to assess the risk of transmission in congregate spaces. We deployed active air samplers to monitor the presence of SARS-CoV-2 in real-world settings across communities in the Upper Midwestern states of Wisconsin and Minnesota. Over 29 weeks, we collected 527 air samples from 15 congregate settings and detected 106 SARS-CoV-2 positive samples, demonstrating SARS-CoV-2 can be detected in air collected from daily and weekly sampling intervals. We expanded the utility of air surveillance to test for 40 other respiratory pathogens. Surveillance data revealed differences in timing and location of SARS-CoV-2 and influenza A virus detection in the community. In addition, we obtained SARS-CoV-2 genome sequences from air samples to identify variant lineages. Collectively, this shows air surveillance is a scalable, cost-effective, and high throughput alternative to individual testing for detecting respiratory pathogens in congregate settings.

Rehabilitation utilization of non-migrant and migrant persons with back pain: A cohort study using different definitions of migrant background.

Background: Medical rehabilitation (MR) by the German Pension Insurance is approved to maintain and to restore work ability and to avoid disability pensions. Studies on the rehabilitation utilization by people with a migration background (PMB) compared to people without a migration background (non-PMB) showed heterogeneous results, which may be partly due to different definitions of migration status. The aim of this paper was to test whether there are differences in utilization of MR between employed PMB and non-PMB with self-reported back pain. Methods: We used data from a large German cohort study that analyzed the effectiveness of MR for individuals with back pain and was conducted between 1st January 2017 and 31st December 2019. Employees aged 45 to 59 years who reported back pain in the last three months completed the baseline questionnaire in 2017. We used four definitions of migration background (MB) to differentiate by first- and second-generation migration, by one- and two-sided migration background, by language, or by nationality. Data on rehabilitation utilization was extracted from administrative records covering the period until the end of 2018. Findings: Data of 6,713 participants were included, and 514 individuals utilized MR during follow-up. Adjusted analyses showed a decreased risk of rehabilitation utilization in people with a first-generation MB (HR = 0·46; 95% CI 0·29; 0·72), people with a two-sided MB (HR = 0·47; 95% CI 0·31; 0·72), people whose native language was not German (HR = 0·52; 95% CI 0·30; 0·91), and people without German nationality (HR = 0·29; 95% CI 0·12; 0·72) when compared to non-PMB. Interpretation: This study showed that employees with a MB reporting back pain had a significantly reduced risk for utilization of rehabilitation services. This underutilization could be observed considering different definitions of MB. Future research on rehabilitation utilization by PMB should consider the impact of different definitions on the results. Funding: The study was funded by the German Research Foundation (grant numbers: BE 5885/2-1; MA 6981/2-1). The German Research Foundation functions as a self-governing institution for the promotion of science and research in Germany.

A regulator's view on AIT clinical trials in the United States and Europe: Why successful studies fail to support licensure.

Clinical studies demonstrate that efficacy and safety in allergen immunotherapy (AIT) are linked to a multiplicity of factors decisively influencing success or failure. In recent years, numerous trials were performed with correspondent study results published. Yet, the number of AIT products successfully obtaining licensure in the analogous time frame is comparably limited. Essential for licensure is that the AIT product investigated remains comparable in its qualitative and quantitative composition throughout the clinical development. Verification of efficacy is not solely demonstrated by a statistically significant difference between the test and control populations; it must also be shown to be clinically relevant. Choice of meaningful inclusion and end-point criteria is critical. Post hoc or subgroup analysis can be supportive but needs verification as predefined criteria in additional studies. Data analysis may be presented on varying analysis populations, while it should be based on the intention-to-treat population for regulatory review to allow objective assessment of the treatment effect on the overall study population. Apparently conflicting interpretations of clinical data between publications and regulatory review are frequently based on their inherently different objectives, with regulatory review taking into considerations the full data sets of all relevant clinical studies for the concerned AIT product to allow an informed decision on licensure.

Barriers to applying for medical rehabilitation: a time-to-event analysis of employees with severe back pain in Germany.

OBJECTIVE: Longitudinal studies on barriers to applying for rehabilitation in Germany are lacking in light of the suspected underutilization of rehabilitation services. The aim of this study was to examine application behaviour in persons with disabling back pain and to identify relevant predictors for making an application. DESIGN: A prospective cohort study with randomized sampling of insurants in the German Pension Insurance, using a questionnaire at baseline and follow-up with linked administrative data for 1.5 years. SUBJECTS/PATIENTS: Employed persons (age range 45-59 years) with a high degree of limitations due to back pain and a self-reported risk of permanent work disability (not applied for disability pension, no medical rehabilitation within the last 4 years). METHODS: Multivariable Cox regression was used to examine the influence of pre-selected variables on making an application in the follow-up period. RESULTS: Of 690 persons, only 12% applied for rehabilitation. Predictors for making an application were: support from physicians (hazard ratio (HR)=2.24; 95% confidence interval (95% CI) 1.32-3.80), family, and friends (HR=1.67; 95% CI 1.02-2.73), more pain-related disability days (HR=1.02; 95% CI 1.01-1.03), and worse work ability (HR=0.86; 95% CI 0.75-0.97). An intention to apply at baseline mediated the effect of family and physician support on the application. CONCLUSION: The low number of applications for rehabilitation despite disabling back pain indicates access barriers to, and underuse of, medical rehabilitation.

Effectiveness of medical rehabilitation in persons with back pain - lessons learned from a German cohort study.

PURPOSE: Evidence for health-related effects of German medical rehabilitation programs for back pain is inconclusive. This cohort study aimed to examine the effectiveness of medical rehabilitation in residents with back pain (German Clinical Trial Register: DRKS00011554). MATERIAL AND METHODS: A sample of 45 000 people aged 45-59 years was randomly drawn from two pension agencies. We used propensity score matching to compare persons with back pain who completed a medical rehabilitation program with similar untreated subjects. Questionnaire data were assessed in 2017 and 2019, and linked with administrative data. The primary outcome was pain disability. RESULTS: In total, 6610 persons with back pain were considered for matching and we finally compared 200 persons treated in a medical rehabilitation program with 200 untreated subjects. Pain disability was reported more favorable in the control group without medical rehabilitation compared to the intervention group (difference = 4.2; 95% CI -0.8-9.2), as well as other secondary outcomes. CONCLUSIONS: At first glance, the findings suggest that medical rehabilitation was ineffective in improving health, pain and work ability among employed persons with back pain, but we found plausible explanations indicating that the estimated effects in favor of the untreated subjects are methodologically induced.IMPLICATIONS FOR REHABILITATIONPropensity score matching can be used to assess the effects of multimodal interventions in persons with back pain in routine care.Inappropriate recruitment of controls may underestimate treatment effects.When using observational data and propensity score matching to analyze the effectiveness of medical rehabilitation, baseline survey should be conducted directly before the start of rehabilitation to identify comparable controls.

Self-Reported Prognosis of Employability as an Indicator of Need for Rehabilitation: A Cohort Study in People with Back Pain.

PURPOSE: Rehabilitation is a key strategy to enable people with disabilities or chronic diseases to participate in society and employment. In Germany, the approval of rehabilitation services is linked to personal requirements, including significantly compromised work ability due to illness. The subjective prognosis of employability (SPE) is a brief 3-item scale. The total score assesses the self-rated risk of permanent work disability and was therefore proposed to be an indicator to operationalize the requirements to determine the need for a medical rehabilitation measure. This cohort study examined whether rehabilitation and disability pensions can be predicted by the SPE in employees with back pain. Moreover, the study tested the applicability of the SPE regarding interrupted employment. METHODS: Employees aged 45 to 59 years who reported back pain in the last three months completed the SPE in 2017. The total score ranges from 0 to 3 points, with higher values indicating a higher risk of permanent work disability. Data on rehabilitation, disability pensions, and interrupted employment were extracted from administrative records covering the period until the end of 2018. Proportional hazard and logistic regression models were fitted. RESULTS: Data of 6,742 participants were included (mean age: 52.3 years; 57.8% women). Maximum follow-up was 21 months. Of the participants, 38.8, 33.6, 21.4, and 6.2% had an SPE score of 0, 1, 2, and 3 points, respectively. During follow-up, 535 individuals were approved for a rehabilitation measure and 49 individuals for a disability pension. Fully adjusted analyses showed an increased risk of a rehabilitation in employees with an SPE score of 3 points (HR=2.20; 95% CI 1.55; 3.11) and 2 points (HR=1.76; 95% CI 1.33; 2.31) compared to employees with an SPE score of 0 points. The risk of a disability pension (HR=13.60; 95% CI 4.56; 40.57) and the odds of interrupted employment (OR=2.58; 95% CI 1.72; 3.86) were also significantly increased for those with an SPE score of 3 points. CONCLUSIONS: The brief SPE is an appropriate tool to identify individuals reporting back pain at risk of rehabilitation, poor work participation outcomes, and permanent work disability. HINTERGRUND: Rehabilitation ist eine Schlüsselstrategie, um Menschen mit Behinderungen oder chronischen Erkrankungen die Teilhabe an der Gesellschaft und am Arbeitsleben zu ermöglichen. In Deutschland ist die Bewilligung von Rehabilitationsleistungen an persönliche Voraussetzungen geknüpft, u. a. an eine erhebliche Gefährdung der Erwerbsfähigkeit aufgrund von Krankheit. Die subjektive Erwerbsprognose (SPE) ist eine kurze 3-Item-Skala. Der Gesamtscore bewertet das selbst eingeschätzte Risiko einer dauerhaften Arbeitsunfähigkeit und wurde daher als Indikator zur Operationalisierung der Voraussetzungen und zur Bestimmung des Bedarfs an einer medizinischen Rehabilitationsmaßnahme vorgeschlagen. Die Kohortenstudie untersucht, inwiefern Rehabilitationen und Erwerbsminderungsrenten durch die SPE bei Beschäftigten mit Rückenschmerzen vorhergesagt werden können. Zudem wurde die Assoziation zwischen der SPE und unterbrochener Beschäftigung getestet. METHODEN: Die SPE wurde im Jahr 2017 bei Versicherten im Alter von 45 bis 59 Jahren, die Rückenschmerzen in den letzten drei Monaten berichteten, erhoben. Der Gesamtscore reicht von 0 bis 3 Punkten, wobei höhere Werte ein höheres Risiko für eine dauerhafte Erwerbsunfähigkeit anzeigen. Daten zu Rehabilitationen, Erwerbsminderungsrenten und unterbrochener Beschäftigung umfassen den Zeitraum bis Ende 2018 und wurden aus den Versichertenkonten extrahiert. Die Zusammenhänge wurden mittels proportionaler Hazard- und logistischer Regressionsmodelle getestet. ERGEBNISSE: Es wurden die Daten von 6.742 Teilnehmenden eingeschlossen (mittleres Alter: 52,3 Jahre; 57,8% weiblich). Der maximale Nachbeobachtungszeitraum betrug 21 Monate. 38,8, 33,6, 21,4 und 6,2% hatten einen SPE-Score von 0, 1, 2 bzw. 3 Punkten. Im Beobachtungszeitraum wurde 535 Personen eine Rehabilitationsmaßnahme und 49 Personen eine Erwerbsminderungsrente bewilligt. Vollständig adjustierte Analysen zeigten ein erhöhtes Risiko für eine Rehabilitation bei Beschäftigten mit einer SPE von 3 Punkten (HR=2,20; 95% KI 1,55; 3,11) und 2 Punkten (HR=1,76; 95% KI 1,33; 2,31) im Vergleich zu Personen mit einer SPE von 0 Punkten. Das Risiko einer Erwerbsminderungsrente (HR=13,60; 95% KI 4,56; 40,57) und die Wahrscheinlichkeit für eine unterbrochene Beschäftigung (OR=2,58; 95% KI 1,72; 3,86) waren ebenfalls signifikant erhöht für diejenigen mit einer SPE von 3 Punkten. SCHLUSSFOLGERUNGEN: Die SPE ist bei Menschen mit selbstberichteten Rückenschmerzen ein geeignetes Assessmentinstrument zur Identifizierung von Personen, bei denen ein erhöhtes Risiko für eine Rehabilitation, gefährdete berufliche Teilhabe und dauerhafte Arbeitsunfähigkeit besteht.

The role of different nephrology experts in informed shared decision-making for renal replacement therapy.

BACKGROUND: Interprofessional teams and peer support are being increasingly considered in informed shared decision-making. In Germany, there appear to be deficits in the implementation of informed shared decision-making in the choice of renal replacement therapy, such as the lack of collaboration in interprofessional teams and the absence of structured peer support programmes for patients with chronic kidney disease. OBJECTIVE: To explore nephrologists' and nurses' perspectives regarding their involvement in shared decision-making when choosing renal replacement therapy. DESIGN: Guideline-based, problem-centred interviews were used. PARTICIPANTS: A total of 20 nephrologists and 15 nurses were recruited from 21 dialysis units all over Germany. APPROACH: Interviews were audio-recorded and transcribed. They were analysed thematically using structuring and summary content analysis, supported by the qualitative data analysis software MAXQDA 12. RESULTS: The most important findings were the late or missing participation of nurses in the informed shared decision-making process and the unstructured peer support. Along with time and financial factors, these aspects were seen as barriers to shared decision-making with patients who are often overwhelmed by the diagnosis. Furthermore, informed shared decision-making has been insufficiently considered in professional education and training. CONCLUSION: Shared decision-making in the choice of renal replacement therapy is particularly challenging due to the patients' high disease burden. The greater incorporation of informed shared decision-making in education and training as well as the consistent involvement of nursing staff and structured peer counselling already in the predialysis phase with adequate reimbursement can address the identified hurdles.

Standardisation of allergen products: 4. Validation of a candidate European Pharmacopoeia standard method for quantification of major grass pollen allergen Phl p 5.

BACKGROUND: The aim of the BSP090 project is the establishment of European Pharmacopoeia Chemical Reference Substances (CRSs) in combination with corresponding standard ELISA methods for quantification of major allergens in allergen products. Here, we present data of a Phl p 5-specific sandwich ELISA that proved suitable for the quantification of Phl p 5, one of the major Timothy grass (Phleum pratense) pollen allergens. METHODS: A Phl p 5-specific ELISA system was assessed with respect to accuracy, precision, inter-assay (within laboratory) and inter-laboratory variations, in a ring trial including 14 laboratories in Europe and the USA. Model samples containing recombinant Phl p 5a CRS as well as native grass pollen extracts were analysed. Each participant was instructed to perform at least one preliminary assay to familiarise with the protocol, followed by three independent assays. RESULTS: The candidate standard ELISA proved suitable to quantify recombinant and native Phl p 5 with satisfactory precision (93% of results within ±30% acceptance range). Inter-assay variation (max. GCV 24%) and especially inter-laboratory variation (max. GCV 13%) showed conclusive results. When assessing accuracy by means of recovery of recombinant spikes from a grass pollen extract matrix, similarly satisfactory spike recovery results were observed for the two spikes with higher concentrations (all within ±30% acceptance range), whereas recovery of the lowest concentration spike was slightly poorer with mean results of six laboratories exceeding acceptance range. CONCLUSIONS: Based on the collaborative study results, the assessed Phl p 5-specific immunoassay is appropriate to be proposed as European Pharmacopoeia standard method.

RENaBack: low back pain patients in rehabilitation-study protocol for a multicenter, randomized controlled trial.

BACKGROUND: Millions of people in Germany suffer from chronic pain, in which course and intensity are multifactorial. Besides physical injuries, certain psychosocial risk factors are involved in the disease process. The national health care guidelines for the diagnosis and treatment of non-specific low back pain recommend the screening of psychosocial risk factors as early as possible, to be able to adapt the therapy to patient needs (e.g., unimodal or multimodal). However, such a procedure has been difficult to implement in practice and has not yet been integrated into the rehabilitation care structures across the country. METHODS: The aim of this study is to implement an individualized therapy and aftercare program within the rehabilitation offer of the German Pension Insurance in the area of orthopedics and to examine its success and sustainability in comparison to the previous standard aftercare program. The study is a multicenter randomized controlled trial including 1204 patients from six orthopedic rehabilitation clinics. A 2:1 allocation ratio to intervention (individualized and home-based rehabilitation aftercare) versus the control group (regular outpatient rehabilitation aftercare) is set. Upon admission to the rehabilitation clinic, participants in the intervention group will be screened according to their psychosocial risk profile. They could then receive either unimodal or multimodal, together with an individualized training program. The program is instructed in the clinic (approximately 3 weeks) and will continue independently at home afterwards for 3 months. The success of the program is examined by means of a total of four surveys. The co-primary outcomes are the Characteristic Pain Intensity and Disability Score assessed by the German version of the Chronic Pain Grade questionnaire (CPG). DISCUSSION: An improvement in terms of pain, work ability, patient compliance, and acceptance in our intervention program compared to the standard aftercare is expected. The study contributes to provide individualized care also to patients living far away from clinical centers. TRIAL REGISTRATION: DRKS, DRKS00020373 . Registered on 15 April 2020.

The History, Present and Future of Allergen Standardization in the United States and Europe.

The topic of standardization in relation to allergen products has been discussed by allergists, regulators, and manufacturers for a long time. In contrast to synthetic medicinal products, the natural origin of allergen products makes the necessary comparability difficult to achieve. This holds true for both aspects of standardization: Batch-to-batch consistency (or product-specific standardization) and comparability among products from different manufacturers (or cross-product comparability). In this review, we focus on how the United States and the European Union have tackled the topic of allergen product standardization in the past, covering the early joint standardization efforts in the 1970s and 1980s as well as the different paths taken by the two players thereafter until today. So far, these two paths have been based on rather classical immunological methods, including the corresponding benefits like simple feasability. New technologies such as mass spectrometry present an opportunity to redefine the field of allergen standardization in the future.

Validation and Application of an HPLC-UV Method for Routine Therapeutic Drug Monitoring of Cefiderocol.

Cefiderocol is a new siderophore cephalosporin approved for the treatment of multidrug resistant bacteria including activity against carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa. As cephalosporins are known for their high pharmacokinetic variability in critically ill patients, cefiderocol therapeutic drug monitoring might become a valuable tool. Therefore, we aimed to develop and validate a simple, rapid, cost-effective high performance liquid chromatography (HPLC) method for the quantification of cefiderocol in serum. Samples were treated for protein precipitation followed by chromatographic separation on a reverse phase column (HPLC C-18) with gradient elution of the mobile phase. Cefiderocol was detected via UV absorption and quantification was performed with the internal standard (metronidazole) method. The calibration range showed linearity from 4 to 160 mg/L. The intra and interday precision was less than 10% with a recovery rate of 81%. The method was successfully used for the analysis of subsequent serum samples of critically ill patients and showed good performance in monitoring serum levels and optimizing antibiotic therapy.