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Background: Previous reports suggest that blood donors have a lower mortality risk, which may partially reflect the "healthy donor effect" (HDE). HDE arises in donors due to selection bias and confounding if not appropriately addressed. Study Design and Methods: Using the Sax Institute's 45 and Up Study data linked with blood donation history, we used a "5‐year exposure window" method to select donors into regular high‐frequency whole blood (WB)donors (at least two donations per exposure year) and low‐frequency donors (remaining donors) with an active donation career of 5 years. To further reduce the confounding, we used statistical approaches like the inverse probability weighted (IPW) marginal structural model and the doubly robust targeted minimum loss‐based estimator (TMLE), which incorporated machine learning algorithms and time‐varying analyses. Results: We selected 4750 (64.7%) low‐frequency and 2588 (35.3%) high‐frequency donors in the analyses. A total of 69 (1.5%) from the low‐frequency and 45 (1.7%) donors from the regular high‐frequency group died during the 7‐year follow‐up period. We did not find any statistically significant association between regular high‐frequency blood donation and mortality (IPW RR = 0.98 95% CI 0.68, 1.28). TMLE model also showed similar results to IPW (RR = 0.97 95% CI 0.80, 1.16). Time‐varying TMLE did not find any significant association between high‐frequency donation and all‐cause mortality either (RR = 0.98 95% 0.74, 1.29). Conclusions: We did not find a significant association between regular high‐frequency WB donation and all‐cause mortality when appropriate methods were employed to minimize the HDE. [ABSTRACT FROM AUTHOR]

Background and Objectives: Several studies have suggested that blood donors have lower risk of gastrointestinal and breast cancers, whereas some have indicated an increased risk of haematological cancers. We examined these associations by appropriately adjusting the 'healthy donor effect' (HDE). Materials and Methods: We examined the risk of gastrointestinal/colorectal, breast and haematological cancers in regular high‐frequency whole blood (WB) donors using the Sax Institute's 45 and Up Study data linked with blood donation and other health‐related data. We calculated 5‐year cancer risks, risk differences and risk ratios. To mitigate HDE, we used 5‐year qualification period to select the exposure groups, and applied statistical adjustments using inverse probability weighting, along with other advanced doubly robust g‐methods. Results: We identified 2867 (42.4%) as regular high‐frequency and 3888 (57.6%) as low‐frequency donors. The inverse probability weighted 5‐year risk difference between high and low‐frequency donors for gastrointestinal/colorectal cancer was 0.2% (95% CI, −0.1% to 0.5%) with a risk ratio of 1.25 (0.83–1.68). For breast cancer, the risk difference was −0.2% (−0.9% to 0.4%), with a risk ratio of 0.87 (0.48–1.26). Regarding haematological cancers, the risk difference was 0.0% (−0.3% to 0.5%) with a risk ratio of 0.97 (0.55–1.40). Our doubly robust estimators targeted minimum loss‐based estimator (TMLE) and sequentially doubly robust (SDR) estimator, yielded similar results, but none of the findings were statistically significant. Conclusion: After applying methods to mitigate the HDE, we did not find any statistically significant differences in the risk of gastrointestinal/colorectal, breast and haematological cancers between regular high‐frequency and low‐frequency WB donors. [ABSTRACT FROM AUTHOR]

Background: The healthy donor effect (HDE) is a selection bias caused by the health criteria blood donors must meet. It obscures investigations of beneficial/adverse health effects of blood donation and complicates the generalizability of findings from blood donor cohorts. To further characterize the HDE we investigated how self‐reported health and lifestyle are associated with becoming a blood donor, lapsing, and donation intensity. Furthermore, we examined differences in mortality based on donor status. Study Design and Methods: The Danish National Health Survey was linked to the Scandinavian Donations and Transfusions (SCANDAT) database and Danish register data. Logistic‐ and normal regression was used to compare baseline characteristics and participation. Poisson regression was used to investigate future donation choices. Donation intensity was explored by the Anderson‐Gill model and Poisson regression. Mortality was investigated using Poisson regression. Results: Blood donors were more likely to participate in the surveys, OR = 2.45 95% confidence interval (2.40–2.49) than non‐donors. Among survey participants, better self‐reported health and healthier lifestyle were associated with being or becoming a blood donor, donor retention, and to some extent donation intensity, for example, current smoking conveyed lower likelihood of becoming a donor, OR = 0.70 (0.66–0.75). We observed lower mortality for donors and survey participants, respectively, compared with non‐participating non‐donors. Conclusion: We provide evidence that blood donation is associated with increased likelihood to participate in health surveys, possibly a manifestation of the HDE. Furthermore, becoming a blood donor, donor retention, and donation intensity was associated with better self‐reported health and healthier lifestyles. [ABSTRACT FROM AUTHOR]

Peffer et al. first proposed the 10-year qualification period method (i.e., all donors must have donated for at least 10 years to be qualified for the study) as a means to adjust for HDE.29,33 In this method, the authors adjusted HDE by introducing 10-years qualification period where donors must remain an active donor for at least 10 years. (HDE, healthy donor effect) [Color figure can be viewed at wileyonlinelibrary.com] gl Of the 27 studies, 3 (11%) did not use any method that could mitigate the HDE while the rest of the studies used one or more methods that could potentially mitigate the HDE. Keywords: blood donors; HDE; health outcomes; healthy donor effect EN blood donors HDE health outcomes healthy donor effect 698 712 15 03/23/22 20220301 NES 220301 Abbreviations ANOVA Analysis of Variance BCAs Blood Collection Agencies BMI body mass index BMD bone mineral density CVD cardiovascular disease HDE healthy donor effect HRE healthy registration effect HDSE healthy donor survivor effect HDCE healthy donor career effect LRS leukoreduction system MPNs myeloproliferative neoplasms PV polycythemia vera SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 BACKGROUND Blood donation is a life-saving act for patients in need of blood products. Health outcomes, healthy donor effect, blood donors, HDE. [Extracted from the article]

SUMMARY: Aims: This study aimed at quantifying the healthy donor effect by comparing self‐perceived mental and physical health between blood donors and non‐donors. Background: In theory, the selection process known as the healthy donor effect should result in better self‐perceived, health‐related quality of life in donors than in non‐donors. Methods: The Short Form‐12 data from the Danish Twin Registry (DTR) was compared with the data from the Danish Blood Donor Study (DBDS). Data on age, sex and smoking status were included in the analyses. The multivariable linear regression analysis was stratified by sex and age group intervals. Outcome variables were the mental component score (MCS) and the physical component score (PCS). Results: A total of 28 982 and 36 913 participants from the DTR and the DBDS, respectively, were included in this study. Younger donors had higher MCS than non‐donors, whereas MCS was only marginally high in older donors compared with non‐donors. In contrast, PCS was almost similar for both young donors and non‐donors. With the increase in age, non‐donors had lower PCS than donors. Conclusions: Two selection patterns were revealed. Among young individuals, better self‐perceived mental health was associated with a blood donor. With the increase in age, better self‐perceived physical health was associated with blood donation. [ABSTRACT FROM AUTHOR]