A Danish national, multicentre evaluation of the new donor vigilance system among different staff groups.

BACKGROUND AND OBJECTIVES: Two years after implementing a new national donor vigilance system, the Danish Haemovigilance Committee conducted a nationwide survey to evaluate the implementation among different staff groups. We present the results here. MATERIALS AND METHODS: The study was designed as an anonymous online survey to evaluate the satisfaction with the new registration, understanding of the parameters used and the user-friendliness. The REDCap platform was used. The questionnaire consisted of 22 questions. Ordinal variables were answered using five-point Likert scale (1 = strongly disagree to 5 = strongly agree). The data were analysed using descriptive statistics. Successful implementation was defined as mean overall satisfaction ≥4 and mean understanding of the individual components (adverse reaction category, severity and imputability) in the registration ≥4. RESULTS: In all, 104 staff members (77.9% donation staff) participated. The mean (SD) overall satisfaction among all participants was 3.96 (0.94), highest among medical doctors (4.43 (0.78)) and lowest for administrative or other personnel (2.78 (1.09)). The mean scores for understanding the adverse reaction categories, severity and imputability were 3.92 (0.94), 3.92 (0.94) and 3.88 (1.00), respectively. Experience with a previous donor vigilance system was associated with lower scores. The most successful implementation programme included a medical doctor for introduction and a contact person. CONCLUSION: The goal for successful implementation was not met. However, the overall attitude towards the new registration was positive and indicates that the system is suitable for different staff groups. Our results suggest that implementation could benefit from special attention to administrative staff and those accustomed to another donor vigilance system.

The safety and performance of the Spectra Optia apheresis system platelet depletion protocol in patients with elevated platelet counts.

BACKGROUND: Thrombocytosis is a presenting and progressive clinical feature found in multiple disease states. It is characterized by high platelet (PLT) counts (>450 × 109 /L) and can lead to thrombohemorrhagic events. Thrombocytapheresis or platelet depletion (PLTD) can be performed in acutely symptomatic patients suffering from thrombocytosis and may reduce or prevent acute serious complications associated with thrombocythemia thereby enabling patients to receive potentially curative high-dose chemotherapy. METHODS: This report details the results from 2 clinical studies, one conducted in the European Union (EU) and one in the People's Republic of China, assessing the PLTD procedure on the Spectra Optia Apheresis System. The primary objective of both studies was to assess the safety and performance of the PLTD procedure in patients with elevated PLT counts. RESULTS: Data were collected from 56 participants completing 64 PLTD procedures. The mean percent change in PLT count and collection efficiency (CE1) was 55.1% and 68.5%, respectively. In the EU study, 6 participants experienced a total of 9 adverse events (AEs) and in the China study, 44 participants reported a total of 212 AEs. In both studies, the majority of AEs reported were Grade 2 or lower and no serious AEs, unanticipated adverse device effects, or AEs leading to death were reported. CONCLUSIONS: The data collected within these studies indicate that the PLTD procedure is well tolerated and effective at reducing circulating PLTs in patients suffering from thrombocytosis as evaluated by a percent decrease in PLT count, CE1, and AE incidence.

Hyperhidrosis and human leucocyte antigens in the Danish Blood Donor Study.

Familial clustering of the skin disease primary hyperhidrosis suggests a genetic component to the disease. The human leucocyte antigen (HLA) is implicated in a range of diseases, including many comorbidities to hyperhidrosis. No study has investigated whether the HLA genes are involved in the pathogenesis of hyperhidrosis. We, therefore, compared HLA alleles in individuals with and without hyperhidrosis in this study of 65 000 blood donors. In this retrospective cohort study, we retrieved information on individuals with and without hyperhidrosis using self-reported questionnaires, the Danish National Patient Registry and the Danish National Prescription Registry on participants recruited to the Danish Blood Donor Study between 2010 and 2019. Association tests using logistic regression were conducted for each HLA allele corrected for sex, age, body mass index, smoking and principal components. Overall, 145 of 65 795 (0.2%) participants had hospital diagnosed hyperhidrosis. Similarly, 1379 of 15 530 (8.9%) participants had moderate-severe self-reported hyperhidrosis, of whom 447 (2.9%) had severe self-reported hyperhidrosis. Altogether, 28 participants had both hospital diagnosed and moderate-severe self-reported hyperhidrosis. Severe self-reported hyperhidrosis was associated with HLA-A*80:01 (adjusted odds ratio 26.97; 95% confidence interval 5.32-136.70; n = 7; P < .001). Moderate-severe self-reported hyperhidrosis and hospital diagnosed hyperhidrosis were not associated with any HLA. The association between hyperhidrosis and HLA-A*80:01 was based on a very small number of cases and not replicated in other patient subsets, and therefore likely a chance finding. Thus, this study suggests that genes other than the HLA are involved in the pathogenesis of hyperhidrosis.

The new donor vigilance system in Denmark reveals regional differences in adverse reactions supposedly caused by variation in the registration.

BACKGROUND AND OBJECTIVES: In recent years, there has been an increased focus among blood bank professionals on the health and safety of blood donors. In 2019, the Danish Haemovigilance Committee designed a national donor vigilance system to improve the registration of adverse reactions (AR) in blood donors. The new donor vigilance system was implemented on 1 January 2020 and we here present the results from the first year of registration. MATERIALS AND METHODS: AR categories, severity level and imputability score were defined based on the definitions from the International Society of Blood Transfusion, AABB and the European Commission directive 2005/61/EC, respectively. RESULTS: Across all severity levels, AR in Danish blood donors were found to be rare (1498 per 100,000 donations). Only 0.2% of the registered reactions were classified as serious (2.7 per 100,000 donations). Large regional differences were seen in the registration of citrate reactions and haematomas. CONCLUSION: Significant differences across regions in what to categorize as an AR were persistent even when including a severity score in the reporting. The Danish Haemovigilance Committee will commence a national work to align the definitions but suggests that this matter is raised to an international level as part of the current work to agree upon definitions for assessment of donor AR.

Ultrasound-guidance of peripheral venous catheterization in apheresis minimizes the need for central venous catheters.

INTRODUCTION: Central venous catheters (CVC) can facilitate a reliable blood flow for apheresis procedures, but the placement is time-consuming and costly and the incidence of catheter-related complications is high. Ultrasound can aid nurses to insert peripheral venous catheters (PVC), which is safer for the patients. METHODS AND MATERIALS: We evaluated the use of CVC vs PVC for all apheresis procedures 3 years after the implementation of structured training of apheresis nurses to perform ultrasound-guided PVC. Ultrasound can visualize the needle tip and target vessel dynamically and guide peripheral venous catheterization with an increased success rate. Time consumption for PVC insertion was measured. RESULTS: In 10 months, we performed 1294 apheresis procedures on 227 patients, where 97.4% were performed with PVC. Hundred percent of extracorporeal photophoresis (off-line ECP) and peripheral blood stem cell collections on adults were performed with PVC. Patients who were treated with CVC (n = 8) were either children, had poor peripheral blood flow due to dehydration or admitted to an intensive care unit and had CVC for other reasons. Time consumption for PVC placement with ultrasound was 11 minutes on average. CONCLUSION: Training of apheresis nurses in ultrasound-guided peripheral venous catheterization can enable close to 100% of apheresis procedures to be performed by PVC.

Clinical impact of clonal hematopoiesis in patients with lymphoma undergoing ASCT: a national population-based cohort study.

Clonal hematopoiesis of indeterminate potential (CHIP) is suspected of being a risk factor for patients with cancer. This study aimed to assess the clinical consequences of CHIP in patients with lymphoma intended for high-dose chemotherapy and autologous stem-cell transplantation (ASCT) in a population-based setting. We identified 892 lymphoma patients who had undergone stem cell harvest at all transplant centers in Denmark. A total of 565 patients had an available harvest sample, which was analysed for CHIP by next-generation sequencing, and the median follow-up was 9.1 years. Of the patients who were intended for immediate ASCT, 25.5% (112/440) carried at least one CHIP mutation. In contrast to previous single-center studies CHIP was not associated with inferior overall survival (OS) in multivariate analyses. However, patients with mutations in genes of the DNA repair pathway (PPM1D, TP53, RAD21, BRCC3) had a significant inferior OS (HR after 1 year of follow-up 2.79, 95% confidence interval 1.71-4.56; p < 0.0001), which also was evident in multivariate analysis (p = 0.00067). These patients had also increased rates of therapy-related leukemia and admission to intensive care. Furthermore, in patients who did not undergo immediate ASCT, a significant inferior OS of individuals with DNA repair mutations was also identified (p = 0.003).

Common, intermediate and well-documented HLA alleles in world populations: CIWD version 3.0.0.

A catalog of common, intermediate and well-documented (CIWD) HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1 and -DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two-field) and G group assignments are divided into one of four frequency categories: common (≥1 in 10 000), intermediate (≥1 in 100 000), well-documented (≥5 occurrences) or not-CIWD. Overall 26% of alleles in IPD-IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two-field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well-documented alleles. Full-field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole.

Evaluation of the Sysmex XN automated hematopoietic progenitor cell enumeration for timing of peripheral blood stem cell harvest.

BACKGROUND: Enumeration of stem cells is essential in the management of peripheral blood stem cell (PBSC) harvest. An alternative to the gold standard flow cytometric CD34+ stem cell count is the fully automated hematopoietic stem cell (HPC) count on the Sysmex XN hematology analyzer. MATERIALS AND METHODS: Eighty-nine patients and healthy stem cell donors who underwent PBSC harvest were included in the study. Stem cells were enumerated in pre-harvest peripheral blood and the apheresis yield by both flow cytometric CD34+ stem cell enumeration and by the Sysmex XN HPC count. RESULTS: The Sysmex HPC concentration overestimated the CD34+ stem cell concentration by a ratio of 1.3 in average. The agreement between the two methods was poor at concentration <40 stem cells/µL (Bias: 45 %, 95 % limits of agreement: -71 - 160 %). CD34+ stem cell concentration and HPC concentration correlated well in pre-harvest peripheral blood (R=0.73, slope=0.96). We established a positive cut off >43.5 HPC/µL, where PBSC harvest can be initiated. And a negative cut off <16.5 HPC/µL, where harvest should be postponed or other mobilizing regimens or bone marrow harvest should be considered. 33 % of measurements were in between the negative and positive cut-off and would require a supplementary CD34+ cell count. CONCLUSION: Although Sysmex HPC count correlates well with CD34+ cell count in peripheral blood, the agreement between the two methods is poor, especially at low concentrations, namely in the clinical decision range. Sysmex HPC count as a surrogate for CD34+ cell count should, therefore, be used with caution.

Effects of a settings-based intervention to promote student wellbeing and reduce smoking in vocational schools: A non-randomized controlled study.

RATIONALE: School dropout and health risk behavior such as cigarette smoking represent major problems among students attending upper secondary vocational education. Modifications to the social environment may promote educational attainment as well as health and wellbeing of young people. However, there is a need for more evidence-based intervention programs. OBJECTIVE: The aim of this study was to assess the effectiveness of an intervention targeting the socio-environmental setting at vocational schools on student wellbeing and smoking. METHODS: We conducted a non-randomized controlled trial of 5794 students (mean age 21 years; 81% male) in 10 (four intervention and six comparison) large vocational schools in Denmark. The intervention involved changes in everyday school practices focusing on four themes: (i) introduction activities, (ii) daily class meetings, (iii) scheduled breaks and (iv) pleasant non-smoking environment. Outcomes were student wellbeing (four subscales: school connectedness, student support, teacher relatedness, positive valuing of the profession) and daily smoking measured at 10-week follow-up. RESULTS: We found statistically significant between-group difference in school connectedness, but not in student support, teacher relatedness and valuing the profession. The intervention had no effect on daily smoking. However, we found a statistically significant interaction between baseline smoking status and condition. This interaction suggested that baseline occasional smokers in the intervention group had significantly reduced odds ratio (OR) of becoming a daily smoker compared to baseline occasional smokers in the control group (8% versus 16%; OR = 0.44). CONCLUSION: The positive effects on school connectedness and in preventing occasional smokers becoming daily smokers indicate that it is possible to tackle school-related wellbeing and smoking in a high risk population through settings-based interventions.

Shaping the Social: design of a settings-based intervention study to improve well-being and reduce smoking and dropout in Danish vocational schools.

BACKGROUND: The social environment at schools is an important setting to promote educational attainment, and health and well-being of young people. However, within upper secondary education there is a need for evidence-based school intervention programmes. The Shaping the Social intervention is a comprehensive programme integrating social and educational activities to promote student well-being and reduce smoking and dropout in upper secondary vocational education. The evaluation design is reported here. METHODS/DESIGN: The evaluation employed a non-randomised cluster controlled design, and schools were selected to either implement the intervention or continue with normal practice for comparison. In the baseline survey conducted 2011-2012, 2,329 students from four intervention schools and 3,371 students from six comparison schools answered a computer-based questionnaire during class, representing 73% and 81% of eligible students, and 22% of all technical/agricultural vocational schools in Denmark. Follow-up assessment was conducted 10 weeks after baseline and at the same time teachers of the intervention classes answered a questionnaire about implementation. School dropout rates will be tracked via national education registers through a 2-year follow-up period. DISCUSSION: Shaping the Social was designed to address that students at Danish vocational schools constitute a high risk population concerning health behaviour as well as school dropout by modifying the school environment, alongside developing appropriate evaluation strategies. To address difficulties in implementing settings-based interventions, as highlighted in prior research, the strategy was to involve intervention schools in the development of the intervention. Baseline differences will be included in the effectiveness analysis, so will the impact of likely mediators and moderators of the intervention. TRIALS REGISTRATION: ISRCTN57822968. Date of registration: 16/01/2013.

How can we strengthen students' social relations in order to reduce school dropout? An intervention development study within four Danish vocational schools.

BACKGROUND: This article describes the rationale and contents of an intervention program aimed at strengthening students' social relations in order to reduce dropout from vocational schools in Denmark. Taking its theoretical cue from the concept of 'social participation', a qualitative study was performed to investigate the specific relationships between the social environment within the schools and the institutional structures in order to analyse reasons for school dropout and their relation to well-being, cigarette smoking and substance use. METHODS: The development study was based on ethnographic methods, including 22 qualitative interviews with students 17-19 years old and fieldwork with participant observations at four vocational schools over 40 days, including informal interviews and discussion meetings with managers, teachers, counselors and students. As part of the fieldwork, four additional qualitative interviews and four group interviews were conducted with students 16-25 years old. RESULTS: The qualitative data collection resulted in seven major themes to be addressed in the intervention: social relations, sole focus on professional skills, institutionalized individualization, importance of the introduction period, physical surroundings and schedules, tobacco and cannabis use and communication about drug use. The program addressing these themes incorporates suggestions that are meant to improve how teachers welcome new students, to enable greater integration of social and educational activities and to enhance the capacity of teachers and counselors to deal with drug use problems among students. CONCLUSION: The development of new intervention programs might benefit from adopting a theoretical and methodological perspective that enables a closer exploration of the everyday social practices in which interventions are embedded. Thus, we aimed to create a comprehensive intervention that worked through organizational changes in everyday school practices. Intervention programs must be planned in dialogue and collaboration with practitioners in the field to ensure the pertinence and usability of the program.

Collection of peripheral blood progenitor cells for autologous use: performance enhancements of COBE spectra, auto-PBSC.

Collection of peripheral blood stem cells (PBSC) must be performed in a safe and effective manner. Issues like automation, collection efficiency (CE), and adverse events must be considered. Auto-PBSC (COBE Spectra) is a fully automated program for PBSC collection. Changes in the protocol were made to achieve high CE, low product volume, and resulted in three groups of patients. Standard operating procedures (SOPs) were developed to reduce citrate toxicity and patients with central venous catheter. Twenty patients and 27 collections (Group 1), 88 patients and 112 collections (Group 2), and 158 patients and 194 collections (Group 3) were recorded. The protocol changes increased CE significantly from 31% (Group 1) to 57 and 59% (Group 2 and 3). Adjusting endpoint according to the preapheresis number of CD34+ cells reduced the collection time and the volume of the product significantly (median 227 min and 56 mL) without affecting CE. Mean level of ionized calcium before collection was 1.22 mmol/L, measured in 31 patients. This declined to a mean of 1.07 mmol/L after 1 h of collection and remained unchanged despite continuous calcium infusion. The number of patients with mild symptoms of citrate toxicity was reduced from 20 to 6%. A central venous catheter was used in 15%. Compared to peripheral access no differences in blood flow rate or time to perform the collection were found. Changes in the Auto-PBSC protocol resulted in an improved CE and a small product. SOPs reduced the number of patients with citrate toxicity and with central venous catheter.

RHD positive among C/E+ and D- blood donors in Denmark.

BACKGROUND: Many different partial and weak D types have been reported, and most of these are easily detected by serology. However, 17 Del types have also been described, with a very low expression of the D antigen, only detectable by absorption-elution techniques, and these may elicit the development of an anti-D. A genomic test of C/E+ and D- blood donors was initiated, to be able to categorize them correctly as D+ or -. STUDY DESIGN AND METHODS: We analyzed all C/E+ and D- donors within our donor population of 22,000 donors with an initial test for RHD Exon 10. In case of a positive reaction, the genotype was further analyzed by sequence-specific polymerase chain reaction or nucleotide sequencing of the RHD gene. CONCLUSIONS: Of 233 donors analyzed, seven were found positive for RHD Exon 10, and four of these were Del, corresponding to 1.7%. We report here a new mutation in the RHD gene. A correct assignment of all blood donors as D+ or D- is not possible using serotyping alone; genotyping offers the only exact categorization of all cases.