Efficacy and safety of tixagevimab/cilgavimab as passive immunisation against COVID-19 infections in patients with hematological malignancies.

Monoclonal antibodies, as tixagevimab/cilgavimab, have been introduced as prophylaxis against COVID-19 infections in high-risk populations. However, data on efficacy are limited. This study investigates efficacy and tolerability of tixagevimab/cilgavimab in hematological patients under real-life conditions. Tixagevimab/cilgavimab was administered to 155 hematological patients (March-August 2022) at two Austrian centres. S/RBD-antibody assessments were performed before (T0), four weeks (T1), and six months (T2) after application. Side effects, the occurrence of COVID-19 infections, and the course of S/RBD-antibody titres were analysed retrospectively in relation to clinical variables. 155 hematological patients, who refused tixagevimab/cilgavimab, were included as a control group to compare the frequency of COVID-19 infections. Of all immunised patients (52.3% males; 91% triple vaccinated), 25.8% had a COVID-19 breakthrough infection (76% mild) compared to 43.9% in the control group. Patients with chronic lymphocytic leukaemia (CLL)/lymphoma were at highest risk of a COVID-19 infection (OR = 2.21; 95% CI 1.05-4.65; p = 0.037). After immunisation, a steep increase in median antibody levels (1193.4BAU/ml, IQR 0-2318.94) was observed in 67.8%, followed by a rapid decrease between T1 and T2 (465.95BAU/ml, IQR 0-1900.65.3) with the greatest declines in CLL/lymphoma (848.7BAU/ml, IQR 0-1949.6, p = 0.026). Side-effects occurred in 21.2% (CTCAE I/II). These real-world data indicate that S/RBD antibodies respond rapidly after passive immunisation in all hematological patients without safety concerns. Given the rapid decline in S/RBD antibodies, early booster immunisations should be considered for future scenarios in this vulnerable group.

Randomized comparison between KTd and KRd induction therapy followed by maintenance therapy with K or observation in transplant-ineligible patients with newly diagnosed multiple myeloma.

Randomized comparison between KTd and KRd induction followed by second randomization to carfilzomib in transplant-ineligable patients with newly diagnosed multiple myeloma.

Stroke Volume and Stroke Volume Variation, but not Cardiac Index Is Associated With Survival of Majorly Burned Patients in Early Burn Shock.

Adequate fluid therapy is crucial to maintain organ function after burn trauma. Major burns lead to a systemic response with fluid loss and cardiac dysfunction. To guide fluid therapy, measurement of cardiac pre- and afterload is helpful. Whereas cardiac function is usually measured after admission to intensive care unit (ICU), in this study, hemodynamic monitoring was performed directly after arrival at hospital. We conducted a prospective cohort study with inclusion of 19 patients (male/female 13/6, 55 ± 18 years, mean total body surface area 36 ± 19%). Arterial waveform analysis (PulsioFlexProAqt®, Getinge) was implemented immediately after admission to hospital to measure cardiac pre- and afterload and to guide resuscitation therapy. Cardiac parameters 3.75 (2.67-6.0) h after trauma were normal regarding cardiac index (3.45 ± 0.82) L/min/m², systemic vascular resistance index (1749 ± 533) dyn sec/cm5 m2, and stroke volume (SV; 80 ± 20) mL. Stroke volume variation (SVV) was increased (21 ± 7) % and associated with mortality (mean SVV survivors vs nonsurvivors 18.92 (±6.37) % vs 27.6 (±5.68) %, P = .017). Stroke volume was associated with mortality at the time of ICU-admission (mean SV survivors vs nonsurvivors 90 (±20) mL vs 50 (±0) mL, P = .004). Changes after volume challenge were significant for SVV (24 ± 9 vs19 ± 8%, P = .01) and SV (68 ± 24 vs 76 ± 26 mL, P = .03). We described association of SVV and SV with survival of severely burned patients in an observational study. This indicates high valence of those parameters in the early postburn period. The use of an autocalibrated device enables a very early monitoring of parameters relevant to burn shock survival.

A Standardized Porcine Model for Partial-Thickness Wound Healing Studies: Design, Characterization, Model Validation, and Histological Insights.

Wound healing is a complex process that is still not fully understood despite extensive research. To address this, we aimed to design and characterize a standardized porcine model for the evaluation of wound healing, dressings, cell therapies, and pharmaceutical agents. Using a standardized approach, we examined the wound healing process in 1.2 mm-deep dermatome wounds at defined positions in 11 female pigs. Unlike previous studies that have only described/analyzed selected punch biopsies, we performed and described histological analyses along the complete wound length using quantitative morphometric methods. All animals remained fully healthy following surgery and showed no signs of infection. Our histopathological evaluation using a predetermined grading score and quantitative manual morphometry demonstrated the impact of different tissue sampling methods, sampling sites, and residual dermis thickness on wound healing. Our study presents a reproducible model for wound healing evaluation and demonstrates the usefulness of porcine models for assessing dermal and epidermal wound healing. The use of histological analyses over the complete wound length provides advantages over previous studies, leading to the possibility of a deeper understanding of the wound healing process. This model could potentially facilitate future research on novel wound dressings and local wound healing therapies.

S3 guideline: Diagnosis and treatment of epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis) - Part 2: Supportive therapy of EN in the acute and post-acute stages.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare, predominantly drug-induced, acute life-threatening diseases of skin and mucosae. SJS and TEN are nowadays considered as variants of one disease entity with varying degrees of severity called epidermal necrolysis (EN). EN is associated with high morbidity and mortality and constitutes a major disease burden for affected patients. The guideline "Diagnosis and treatment of epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis)" was developed under systematic consideration of existing scientific literature and in a formal consensus process according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF) to establish an evidence-based framework to support clinical decision-making. The interdisciplinary guideline commission consisted of representatives from various specialist societies and of patient representatives. The guideline is aimed at specialists in the fields of dermatology, ophthalmology, plastic surgery, intensive care, and pediatrics in hospitals and offices, as well as other medical specialties involved in the diagnosis and treatment of EN. The guideline is also aimed at patients, their relatives, insurance funds, and policymakers. The second part is concerned with the topics of supportive therapy in the acute phase of EN and outpatient follow-up treatment.

S3 guideline: Diagnosis and treatment of epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis) - Part 1: Diagnosis, initial management, and immunomodulating systemic therapy.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare, predominantly drug-induced, acute, life-threatening diseases of skin and mucosae. SJS and TEN are nowadays considered variants of one disease entity with varying degrees of severity called epidermal necrolysis (EN). EN is associated with high morbidity and mortality and constitutes a major disease burden for affected patients. The guideline "Diagnosis and treatment of epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis)" was developed under systematic consideration of existing scientific literature and in a formal consensus process according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF) to establish an evidence-based framework to support clinical decision-making. The interdisciplinary guideline commission consisted of representatives from various specialist societies and patient representatives. The guideline is aimed at specialists in the fields of dermatology, ophthalmology, plastic surgery, intensive care, and pediatrics in hospitals and offices, as well as other medical speciallved in the diagnosis and treatment of EN. The guideline is also aimed at patients, their relatives, insurance funds, and policymakers. This first part focuses on the diagnostic aspects, the initial management as well as the immunomodulating systemic therapy.

Cox proportional hazards deep neural network identifies peripheral blood complete remission to be at least equivalent to morphologic complete remission in predicting outcomes of patients treated with azacitidine-A prospective cohort study by the AGMT.

The current gold standard of response assessment in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) is morphologic complete remission (CR) and CR with incomplete count recovery (CRi), both of which require an invasive BM evaluation. Outside of clinical trials, BM evaluations are only performed in ~50% of patients during follow-up, pinpointing a clinical need for response endpoints that do not necessitate BM assessments. We define and validate a new response type termed "peripheral blood complete remission" (PB-CR) that can be determined from the differential blood count and clinical parameters without necessitating a BM assessment. We compared the predictive value of PB-CR with morphologic CR/CRi in 1441 non-selected, consecutive patients diagnosed with MDS (n = 522; 36.2%), CMML (n = 132; 9.2%), or AML (n = 787; 54.6%), included within the Austrian Myeloid Registry (aMYELOIDr; NCT04438889). Time-to-event analyses were adjusted for 17 covariates remaining in the final Cox proportional hazards (CPH) model. DeepSurv, a CPH neural network model, and permutation-based feature importance were used to validate results. 1441 patients were included. Adjusted median overall survival for patients achieving PB-CR was 22.8 months (95%CI 18.9-26.2) versus 10.4 months (95%CI 9.7-11.2) for those who did not; HR = 0.366 (95%CI 0.303-0.441; p < .0001). Among patients achieving CR, those additionally achieving PB-CR had a median adjusted OS of 32.6 months (95%CI 26.2-49.2) versus 21.7 months (95%CI 16.9-27.7; HR = 0.400 [95%CI 0.190-0.844; p = .0161]) for those who did not. Our deep neural network analysis-based findings from a large, prospective cohort study indicate that BM evaluations solely for the purpose of identifying CR/CRi can be omitted.

First review on the selenium status in Germany covering the last 50 years and on the selenium content of selected food items.

INTRODUCTION: Selenium is important for human health. However, the selenium status and selenium intake of the German population has not been recorded in a representative study so far. MATERIAL AND METHODS: Thus, literature from the last 50 years was screened in a systematic way and the results of various studies were pulled together to shed light on the selenium status of the German population. Moreover, the selenium content of selected food items that were either found on the German market or grown in Germany was researched and evaluated. RESULTS: Of 3542 articles identified, 37 studies met the inclusion criteria. These 37 studies comprised a total of 8,010 healthy adults living in Germany with a weighted arithmetic mean of 82 µg/l selenium in plasma or serum. The results will form a basis for interpreting upcoming results from national food consumption surveys. Furthermore, 363 selenium values for 199 food items were identified out of 20 data sources-published or analysed between 2002 and 2019. An estimation of the selenium intake of the German population will be possible with this data in future nutrition surveys.

Efficacy and safety of heterologous booster vaccination with Ad26.COV2.S after BNT162b2 mRNA COVID-19 vaccine in haemato-oncological patients with no antibody response.

Patients with haemato-oncological malignancies are one of the high-risk groups for a severe course in case of COVID-19 infections. Furthermore, vaccination results in significantly lower response rates in haematological malignancies and lower antibody levels in patients with solid cancer. We investigated efficacy and safety of a heterologous booster vaccination with Ad26.COV2.S DNA vector vaccine in haemato-oncological patients without antibody response after double-dose BNT162b2 messenger (m-)RNA COVID-19 vaccine. A total of 32 haemato-oncological non-responders to double-dose BNT162b2 received a heterologous booster vaccination with Ad26.COV2.S. Blood samples were assessed directly before the vaccination (T0) and four weeks after (T1). Safety assessment was performed using a standardised questionnaire. The overall response rate was 31%, with a mean (SD) antibody titre of 693·79 (1 096·99) binding activity units (BAU)/ml. Patients with chronic lymphocytic leukaemia or lymphoma showed a significantly lower response rate (P = 0·048). Adverse events were reported in 29·6% of patients, of which 7·1% were graded as severe, including grade III and IV events following the Common Terminology Criteria of Adverse Events (CTCAE). The heterologous booster vaccination with Ad26.COV2.S led to a serological response in nine out of 29 patients without response after double-dose BNT162b2. Furthermore, the vaccination was safe in our cohort, leading to mainly mild local and systemic reactions. Overall, this vaccination regimen should be further evaluated to increase the response rate in the highly vulnerable population of haemato-oncological patients.

Serological SARS-CoV-2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID-19 vaccine in haematological and oncological patients.

Haemato-oncological patients are at risk in case of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Currently, vaccination is the best-evaluated preventive strategy. In the present study, we aimed to assess serological response, predictive markers, and safety of BNT162b2 in haemato-oncological patients. A total of 259 haemato-oncological patients were vaccinated with two 30 µg doses of BNT162b2 administered 21 days apart. Serological response was assessed by ELECSYS® Anti-SARS-CoV-2-S immunoassay before vaccination, and at 3 and 7 weeks after the first dose (T1, T2). Safety assessment was performed. At T2 spike protein receptor binding domain (S/RBD) antibodies were detected in 71·4% of haematological and in 94·5% of oncological patients (P < 0·001). Haematological patients receiving systemic treatment had a 14·2-fold increased risk of non-responding (95% confidence interval 3·2-63·3, P = 0·001). Subgroups of patients with lymphoma or chronic lymphocytic leukaemia were at highest risk of serological non-response. Low immunoglobulin G (IgG) level, lymphocyte- and natural killer (NK)-cell counts were significantly associated with poor serological response (P < 0·05). Vaccination was well tolerated with only 2·7% of patients reporting severe side-effects. Patients with side-effects developed a higher S/RBD-antibody titre compared to patients without side-effects (P = 0·038). Haematological patients under treatment were at highest risk of serological non-response. Low lymphocytes, NK cells and IgG levels were found to be associated with serological non-response. Serological response in oncological patients was encouraging. The use of BNT162b2 is safe in haemato-oncological patients.

A History of Burn Care.

Burn injuries are still one of the most common and devastating injuries in humans and the treatment of major burns remains a major challenge for physicians worldwide [...].

Oxygen, pH, Lactate, and Metabolism-How Old Knowledge and New Insights Might Be Combined for New Wound Treatment.

Over time, we have come to recognize a very complex network of physiological changes enabling wound healing. An immunological process enables the body to distinguish damaged cells and begin a cleaning mechanism by separating damaged proteins and cells with matrix metalloproteinases, a complement reaction, and free radicals. A wide variety of cell functions help to rebuild new tissue, dependent on energy provision and oxygen supply. Like in an optimized "bio-reactor," disturbance can lead to prolonged healing. One of the earliest investigated local factors is the pH of wounds, studied in close relation to the local perfusion, oxygen tension, and lactate concentration. Granulation tissue with the wrong pH can hinder fibroblast and keratinocyte division and proliferation, as well as skin graft takes. Methods for influencing the pH have been tested, such as occlusion and acidification by the topical application of acidic media. In most trials, this has not changed the wound's pH to an acidic one, but it has reduced the strong alkalinity of deeper or chronic wounds. Energy provision is essential for all repair processes. New insights into the metabolism of cells have changed the definition of lactate from a waste product to an indispensable energy provider in normoxic and hypoxic conditions. Neovascularization depends on oxygen provision and lactate, signaling hypoxic conditions even under normoxic conditions. An appropriate pH is necessary for successful skin grafting; hypoxia can change the pH of wounds. This review describes the close interconnections between the local lactate levels, metabolism, healing mechanisms, and pH. Furthermore, it analyzes and evaluates the different possible ways to support metabolism, such as lactate enhancement and pH adjustment. The aim of wound treatment must be the optimization of all these components. Therefore, the role of lactate and its influence on wound healing in acute and chronic wounds will be assessed.

Rapid enzymatic burn debridement: A review of the paediatric clinical trial experience.

NexoBrid (NXB) has been proven to be an effective selective enzymatic debridement agent in adults. This manuscript presents the combined clinical trial experience with NXB in children. Hundred and ten children aged 0.5 to 18 years suffering from deep thermal burns of up to 67% total body surface area were treated with NXB in three clinical trials. Seventy-seven children were treated with NXB in a phase I/II study, where 92.7% of the areas treated achieved complete eschar removal within 0.9 days from admission. Thirty-three children (17 NXB, 16 standard of care [SOC]) participated in a phase III randomized controlled trial. All wounds treated with NXB achieved complete eschar removal. Time to complete eschar removal (from informed consent) was 0.9 days for NXB vs 6.5 days for SOC (P < .001). The incidence of surgical excision was 7.9% for NXB vs 73.3% for SOC (P < .001). Seventeen of these children participated in a phase III-b follow-up study (9 NXB and 8 SOC). The average long-term modified Vancouver Scar Scale scores were 3.4 for NXB-treated wounds vs 4.4 for SOC-treated wounds (NS). There were no significant treatment-related adverse events. Additional studies are needed to strengthen these results.

Health-related quality of life and patient burden in patients with split-thickness skin graft donor site wounds.

Split-thickness skin grafting is a common procedure to treat different kinds of wounds. This systematic, multicentre, observational, cross-sectional study of adult patients with split-thickness skin graft (STSG) donor site wounds was conducted to evaluate quality of life (QoL) impairments caused by donor site wounds following split-thickness skin grafting. Therefore, 112 patients from 12 wound centres in Germany were examined based on patient and physician questionnaires as well as a physical examination of the donor site wound. Most indications for skin grafting were postsurgical treatment (n = 51; 42.5%) and chronic wounds (n = 47; 39.2%). European QoL visual analoque scale (EQ VAS) averaged 64.7 ± 23.3, European QoL 5 dimensions (EQ-5D) averaged 77.4 ± 30.0. Wound-QoL (range: 0-4) was rated 0.8 ± 0.8 post-surgery and 0.4 ± 0.6 at the time of survey (on average 21 weeks between the time points). Compared to averaged Wound-QoL scores of chronic wounds donor site-related QoL impairments in split-thickness skin-graft patients were less pronounced. There were significant differences in patient burden immediately after surgery compared to the time of the survey, with medium effect sizes. This supports the hypothesis that faster healing of the donor site wound leads to more favourable patient-reported outcomes.

Risk factors for cartilage damage and osteoarthritis of the elbow joint: case-control study and systematic literature review.

INTRODUCTION: This case-control study compares patients with healthy elbows to a group of symptomatic patients with cartilage damage/osteoarthritis. MATERIALS AND METHODS: The control group (n = 126) was recruited during routine medical examinations of patients (general medical offices). Included in the case group were a total of 92 patients who were undergoing arthroscopy as a result of chronic elbow discomfort. All patients were questioned with regard to occupational stress and athletic stress. RESULTS: A significantly increased risk of cartilage damage/osteoarthritis was found with subjectively perceived increased stress in occupational settings: OR = 3.8 (95% CI 2.1-6.7); p < 0.001; for the individual stresses of the elbow joint in occupational settings, the following severities in effects were found: Exposure to heavy work OR = 3.9 (95% CI 2.2-6.8); Force OR = 3.7 (95% CI 2.1-6.5); Vibration OR = 4.6 (95% CI 2.5-8.5); Repetition OR = 9.2 (95% CI 3.6-23.3); p < 0.001. Elbow-stressing sport types represent a potential risk factor for the development of cartilage damage/osteoarthritis of the elbow joint: OR = 2.5 (95% CI 1.3-4.7); p = 0.003. CONCLUSIONS: Cartilage damage/radiographic osteoarthritis of the elbow joint are rare with respect to the overall prevalence of osteoarthritis. In the large number of patients with cartilage damage/radiographic osteoarthritis of the elbow joint, occupational or athletic stress factors and injuries sustained, in addition to other causes (rheumatism, gout), can prove as possible causes of these as secondary to symptomatic forms of osteoarthritis.

Occupational kneeling and squatting: development and validation of an assessment method combining measurements and diaries.

OBJECTIVES: As knee-straining postures such as kneeling and squatting are known to be risk factors for knee disorders, there is a need for effective exposure assessment at the workplace. Therefore, the aim of this study was to develop a method to capture knee-straining postures for entire work shifts by combining measurement techniques with the information obtained from diaries, and thus avoiding measuring entire work shifts. This approach was applied to various occupational tasks to obtain an overview of typical exposure values in current specific occupations. METHODS: The analyses were carried out in the field using an ambulatory measuring system (CUELA) to assess posture combined with one-day self-reported occupational diaries describing the durations of various work tasks. In total, 242 work shifts were measured, representing 81 typical tasks from 16 professions. Knee-straining postures were analysed as daily time intervals for five different postures. The accuracy of the method was examined by comparing the results to measurements of entire work shifts. RESULTS: Unsupported kneeling was the most widely used knee posture in our sample (median 11.4 % per work shift), followed by supported kneeling (3.0 %), sitting on heels (1.1 %), squatting (0.7 %), and crawling (0.0 %). The daily time spent in knee-straining postures varied considerably, both between the individual occupations, within an occupation (e.g. parquet layers: 0.0-88.9 %), and to some extent even within a single task (e.g. preparation work of floor layers (22.0 ± 23.0 %). The applied measuring method for obtaining daily exposure to the knee has been proven valid and efficient randomly compared with whole-shift measurements (p = 0.27). CONCLUSIONS: The daily degree of postural exposure to the knee showed a huge variation within the analysed job categories and seemed to be dependent on the particular tasks performed. The results of this study may help to develop an exposure matrix with respect to occupational knee-straining postures. The tested combination of task-based measurement and diary information may be a promising option for providing a cost-effective assessment tool.

Quality of life and predictors of long-term outcome after severe burn injury.

The aim of this study was to identify the long-term quality of life after severe burn injury. In a prospective longitudinal design, N = 265 burn patients were examined 6, 12, 24, and 36 months after burn injury. A multilevel approach was used to measure stability and change in self-reported health status. Besides injury-related variables, self-report instruments included measures of quality of life, psychological distress, personality, and specific burn outcome measures. Fitting of unconditional growth models indicated that there was significant intra- and inter-individual variation in self-reported physical and mental health short form-12. Over the course of 3 years, participants reported on average a slight improvement of physical quality of life. Physical health was mainly predicted by mobility and level of burn severity. Variance in mental health status was mainly predicted by gender, mobility, neuroticism, level of depression and posttraumatic stress disorder (PTSD)-related avoidance. Thus mobility (i.e., simple abilities) seems a crucial variable for overall quality of life. An early identification and treatment of patients with high levels of depression and PTSD-related avoidance may contribute to better mental health.

Prehospital treatment of severely burned patients: a retrospective analysis of patients admitted to the Berlin burn centre.

BACKGROUND: Prehospital management of severely burned patients is extremely challenging. It should include adequate analgesia, decision-making on the necessity of prehospital endotracheal intubation and the administration of crystalloid fluids. Guidelines recommend immediate transport to specialised burn centres when certain criteria are met. To date, there is still insufficient knowledge on the characteristics of prehospital emergency treatment. We sought to investigate the current practice and its potential effects on patient outcome. METHODS: We conducted a single centre, retrospective cohort analysis of severely burned patients (total burned surface area > 20%), admitted to the Berlin burn centre between 2014 and 2019. The relevant data was extracted from Emergency Medical Service reports and digital patient charts for exploratory data analysis. Primary outcome was 28-day-mortality. RESULTS: Ninety patients (male/female 60/30, with a median age of 52 years [interquartile range, IQR 37-63], median total burned surface area 36% [IQR 25-51] and median body mass index 26.56 kg/m2 [IQR 22.86-30.86] were included. The median time from trauma to ED arrival was 1 h 45 min; within this time, on average 1961 ml of crystalloid fluid (0.48 ml/kg/%TBSA, IQR 0.32-0.86) was administered. Most patients received opioid-based analgesia. Times from trauma to ED arrival were longer for patients who were intubated. Neither excessive fluid treatment (> 1000 ml/h) nor transport times > 2 h was associated with higher mortality. A total of 31 patients (34,4%) died within the hospital stay. Multivariate regression analysis revealed that non-survival was linked to age > 65 years (odds ratio (OR) 3.5, 95% CI: 1.27-9.66), inhalation injury (OR 3.57, 95% CI: 1.36-9.36), burned surface area > 60% (OR 5.14, 95% CI 1.57-16.84) and prehospital intubation (5.38, 95% CI: 1.92-15.92). CONCLUSION: We showed that severely burned patients frequently received excessive fluid administration prehospitally and that this was not associated with more hemodynamic stability or outcome. In our cohort, patients were frequently intubated prehospitally, which was associated with increased mortality rates. Further research and emergency medical staff training should focus on adequate fluid application and cautious decision-making on the risks and benefits of prehospital intubation. TRIAL REGISTRATION: German Clinical Trial Registry (ID: DRKS00033516).

QoL during KTd or KRd induction followed by K maintenance or observation in transplant noneligible patients with newly diagnosed multiple myeloma: Longitudinal and cross-sectional analysis of the randomized AGMT 02 study.

Understanding the impact of induction and maintenance therapy on patients' quality of life (QoL) is important for treatment selection. This study aims to compare patient-reported QoL between patients treated with KTd or KRd induction therapy and K maintenance therapy or observation. QoL was assessed using the EORTC QOL-C 30 and QOL-MY20 questionnaires in the AGMT-02 study, in which 123 patients with newly diagnosed transplant ineligible multiple myeloma were randomized to nine cycles of either KTd or KRd induction therapy, followed by 12 cycles of K maintenance therapy, or observation. Longitudinal assessments showed statistically significant improvements in global health-related QoL, various disease symptoms and pain for both treatment regimens. KTd improved insomnia and fatigue, and KRd improved physical functioning. Cross-sectional comparisons indicated a "slight" superiority of KTd over KRd in several scales, with the exception of higher neuropathy scores with KTd. During maintenance, longitudinal comparisons showed no statistically significant changes. Cross-sectional comparisons revealed a "slight" improvement in cognitive functioning during carfilzomib therapy, but a worsening in most other QoL scales. Induction therapy led to improvements in most QoL items, while maintenance therapy with K maintenance was associated with "slight" or "moderate" impairments in several QoL scales compared with the observation group.

Validity of self-reports of knee-straining activities at work: a field study with 6-month follow-up.

OBJECTIVES: To measure short-term and long-term validity of self-reported duration of kneeling and squatting at work and to examine the possibility of differential misclassification due to knee complaints. METHODS: Work-related kneeling and squatting were analysed for 190 male subjects (mean age, 35.0 and SD, 11.5) in field by both measurements and questionnaires. Posture capturing was performed with an ambulatory measuring system (CUELA). Immediately after the measurement (t(0)), each participant was asked to estimate frequency and duration of five specific knee postures taken during the measurement period. After 6 months (t(1)), the survey was repeated (n = 125). Health status of all subjects was recorded by Nordic questionnaire. Statistical analysis was performed by using nonparametric tests, correlations, and Bland-Altman plots. RESULTS: At both time points, subjects were able to recall the occurrence of knee postures rather well (100.0-57.6% agreement) but many of them failed in quantifying their knee load. We found poor-to-moderate correlations between measurements and self-reports for all examined postures in both surveys (0.23 < ρ < 0.63). The durations of knee postures were both over- and underestimated but overestimations predominated (t(0), 74.7% and t(1), 87.2% overestimations). High-exposed subjects seemed to misjudge their exposure to a greater extent than low-exposed ones, while knee complaints seemed to have no impact on the assessment behaviour. CONCLUSIONS: As our study showed, self-reported knee loading may deviate widely from measured exposure. These limitations of self-reporting emphasise the arguments in favour of using objective data whenever possible, for example by complementing self-reported occurrence of knee postures with quantitative measurement data.