14 research outputs found
Recruitment and representativeness of blood donors in the INTERVAL randomised trial assessing varying inter-donation intervals.
BACKGROUND: The interpretation of trial results can be helped by understanding how generalisable they are to the target population for which inferences are intended. INTERVAL, a large pragmatic randomised trial of blood donors in England, is assessing the effectiveness and safety of reducing inter-donation intervals. The trial recruited mainly from the blood service's static centres, which collect only about 10 % of whole-blood donations. Hence, the extent to which the trial's participants are representative of the general blood donor population is uncertain. We compare these groups in detail. METHODS: We present the CONSORT flowchart from participant invitation to randomisation in INTERVAL. We compare the characteristics of those eligible and consenting to participate in INTERVAL with the general donor population, using the national blood supply 'PULSE' database for the period of recruitment. We compare the characteristics of specific groups of trial participants recruited from different sources, as well as those who were randomised versus those not randomised. RESULTS: From a total of 540,459 invitations, 48,725 donors were eligible and consented to participate in INTERVAL. The proportion of such donors varied from 1-22 % depending on the source of recruitment. The characteristics of those consenting were similar to those of the general population of 1.3 million donors in terms of ethnicity, blood group distribution and recent deferral rates from blood donation due to low haemoglobin. However, INTERVAL participants included more men (50 % versus 44 %), were slightly older (mean age 43.1 versus 42.3 years), included fewer new donors (3 % versus 22 %) and had given more donations over the previous 2 years (mean 3.3 versus 2.2) than the general donor population. Of the consenting participants, 45,263 (93 %) donors were randomised. Compared to those not randomised, the randomised donors showed qualitatively similar differences to those described above. CONCLUSIONS: There was broad similarity of participants in INTERVAL with the general blood donor population of England, notwithstanding some differences in age, sex and donation history. Any heterogeneity of the trial's results according to these characteristics will need to be studied to ensure its generalisability to the general donor population. TRIAL REGISTRATION: Current Controlled Trials ISRCTN24760606 . Registered on 25 January 2012.The trial is funded by NHS Blood and Transplant. The trial’s coordinating centre at the Department of Public Health and Primary Care at the University of Cambridge has received core support from the UK Medical Research Council, the British Heart Foundation and the UK National Institute of Health Research (Cambridge Biomedical Research Centre). Investigators at the University of Oxford have been supported by the Research and Development Programme of NHSBT, the NHSBT Howard Ostin Trust Fund, the UK National Institute of Health Research (Oxford Biomedical Research Centre) through the programme grant NIHR-RP-PG-0310-1004 and the Oxford Biomedical Research Centre.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13063-016-1579-
Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors
Background:
Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries.
Methods:
In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants.
Findings:
45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups.
Interpretation:
Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency.
Funding:
NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation
Comparison of four methods to measure haemoglobin concentrations in whole blood donors (COMPARE): A diagnostic accuracy study.
OBJECTIVE: To compare four haemoglobin measurement methods in whole blood donors. BACKGROUND: To safeguard donors, blood services measure haemoglobin concentration in advance of each donation. NHS Blood and Transplant's (NHSBT) customary method have been capillary gravimetry (copper sulphate), followed by venous spectrophotometry (HemoCue) for donors failing gravimetry. However, NHSBT's customary method results in 10% of donors being inappropriately bled (ie, with haemoglobin values below the regulatory threshold). METHODS: We compared the following four methods in 21 840 blood donors (aged ≥18 years) recruited from 10 NHSBT centres in England, with the Sysmex XN-2000 haematology analyser, the reference standard: (1) NHSBT's customary method; (2) "post donation" approach, that is, estimating current haemoglobin concentration from that measured by a haematology analyser at a donor's most recent prior donation; (3) "portable haemoglobinometry" (using capillary HemoCue); (4) non-invasive spectrometry (using MBR Haemospect or Orsense NMB200). We assessed sensitivity; specificity; proportion who would have been inappropriately bled, or rejected from donation ("deferred") incorrectly; and test preference. RESULTS: Compared with the reference standard, the methods ranged in test sensitivity from 17.0% (MBR Haemospect) to 79.0% (portable haemoglobinometry) in men, and from 19.0% (MBR Haemospect) to 82.8% (portable haemoglobinometry) in women. For specificity, the methods ranged from 87.2% (MBR Haemospect) to 99.9% (NHSBT's customary method) in men, and from 74.1% (Orsense NMB200) to 99.8% (NHSBT's customary method) in women. The proportion of donors who would have been inappropriately bled ranged from 2.2% in men for portable haemoglobinometry to 18.9% in women for MBR Haemospect. The proportion of donors who would have been deferred incorrectly with haemoglobin concentration above the minimum threshold ranged from 0.1% in men for NHSBT's customary method to 20.3% in women for OrSense. Most donors preferred non-invasive spectrometry. CONCLUSION: In the largest study reporting head-to-head comparisons of four methods to measure haemoglobin prior to blood donation, our results support replacement of NHSBT's customary method with portable haemoglobinometry
The INTERVAL trial to determine whether intervals between blood donations can be safely and acceptably decreased to optimise blood supply: study protocol for a randomised controlled trial
Longer-term efficiency and safety of increasing the frequency of whole blood donation (INTERVAL): extension study of a randomised trial of 20 757 blood donors
Background:
The INTERVAL trial showed that, over a 2-year period, inter-donation intervals for whole blood donation can be safely reduced to meet blood shortages. We extended the INTERVAL trial for a further 2 years to evaluate the longer-term risks and benefits of varying inter-donation intervals, and to compare routine versus more intensive reminders to help donors keep appointments.
Methods:
The INTERVAL trial was a parallel group, pragmatic, randomised trial that recruited blood donors aged 18 years or older from 25 static donor centres of NHS Blood and Transplant across England, UK. Here we report on the prespecified analyses after 4 years of follow-up. Participants were whole blood donors who agreed to continue trial participation on their originally allocated inter-donation intervals (men: 12, 10, and 8 weeks; women: 16, 14, and 12 weeks). They were further block-randomised (1:1) to routine versus more intensive reminders using computer-generated random sequences. The prespecified primary outcome was units of blood collected per year analysed in the intention-to-treat population. Secondary outcomes related to safety were quality of life, self-reported symptoms potentially related to donation, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin and other factors. This trial is registered with ISRCTN, number ISRCTN24760606, and has completed.
Findings:
Between Oct 19, 2014, and May 3, 2016, 20 757 of the 38 035 invited blood donors (10 843 [58%] men, 9914 [51%] women) participated in the extension study. 10 378 (50%) were randomly assigned to routine reminders and 10 379 (50%) were randomly assigned to more intensive reminders. Median follow-up was 1·1 years (IQR 0·7–1·3). Compared with routine reminders, more intensive reminders increased blood collection by a mean of 0·11 units per year (95% CI 0·04–0·17; p=0·0003) in men and 0·06 units per year (0·01–0·11; p=0·0094) in women. During the extension study, each week shorter inter-donation interval increased blood collection by a mean of 0·23 units per year (0·21–0·25) in men and 0·14 units per year (0·12–0·15) in women (both p<0·0001). More frequent donation resulted in more deferrals for low haemoglobin (odds ratio per week shorter inter-donation interval 1·19 [95% CI 1·15–1·22] in men and 1·10 [1·06–1·14] in women), and lower mean haemoglobin (difference per week shorter inter-donation interval −0·84 g/L [95% CI −0·99 to −0·70] in men and −0·45 g/L [–0·59 to −0·31] in women) and ferritin concentrations (percentage difference per week shorter inter-donation interval −6·5% [95% CI −7·6 to −5·5] in men and −5·3% [–6·5 to −4·2] in women; all p<0·0001). No differences were observed in quality of life, serious adverse events, or self-reported symptoms (p>0.0001 for tests of linear trend by inter-donation intervals) other than a higher reported frequency of doctor-diagnosed low iron concentrations and prescription of iron supplements in men (p<0·0001).
Interpretation:
During a period of up to 4 years, shorter inter-donation intervals and more intensive reminders resulted in more blood being collected without a detectable effect on donors' mental and physical wellbeing. However, donors had decreased haemoglobin concentrations and more self-reported symptoms compared with the initial 2 years of the trial. Our findings suggest that blood collection services could safely use shorter donation intervals and more intensive reminders to meet shortages, for donors who maintain adequate haemoglobin concentrations and iron stores.
Funding:
NHS Blood and Transplant, UK National Institute for Health Research, UK Medical Research Council, and British Heart Foundation
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Accuracy of UK Rapid Test Consortium (UK-RTC) “AbC-19 Rapid Test” for detection of previous SARS-CoV-2 infection in key workers: test accuracy study
Abstract: Objective: To assess the accuracy of the AbC-19 Rapid Test lateral flow immunoassay for the detection of previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design: Test accuracy study. Setting: Laboratory based evaluation. Participants: 2847 key workers (healthcare staff, fire and rescue officers, and police officers) in England in June 2020 (268 with a previous polymerase chain reaction (PCR) positive result (median 63 days previously), 2579 with unknown previous infection status); and 1995 pre-pandemic blood donors. Main outcome measures: AbC-19 sensitivity and specificity, estimated using known negative (pre-pandemic) and known positive (PCR confirmed) samples as reference standards and secondly using the Roche Elecsys anti-nucleoprotein assay, a highly sensitive laboratory immunoassay, as a reference standard in samples from key workers. Results: Test result bands were often weak, with positive/negative discordance by three trained laboratory staff for 3.9% of devices. Using consensus readings, for known positive and negative samples sensitivity was 92.5% (95% confidence interval 88.8% to 95.1%) and specificity was 97.9% (97.2% to 98.4%). Using an immunoassay reference standard, sensitivity was 94.2% (90.7% to 96.5%) among PCR confirmed cases but 84.7% (80.6% to 88.1%) among other people with antibodies. This is consistent with AbC-19 being more sensitive when antibody concentrations are higher, as people with PCR confirmation tended to have more severe disease whereas only 62% (218/354) of seropositive participants had had symptoms. If 1 million key workers were tested with AbC-19 and 10% had actually been previously infected, 84 700 true positive and 18 900 false positive results would be projected. The probability that a positive result was correct would be 81.7% (76.8% to 85.8%). Conclusions: AbC-19 sensitivity was lower among unselected populations than among PCR confirmed cases of SARS-CoV-2, highlighting the scope for overestimation of assay performance in studies involving only PCR confirmed cases, owing to “spectrum bias.” Assuming that 10% of the tested population have had SARS-CoV-2 infection, around one in five key workers testing positive with AbC-19 would be false positives. Study registration: ISRCTN 56609224
Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease
Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis
Recruitment and representativeness of blood donors in the INTERVAL randomised trial assessing varying inter-donation intervals
BACKGROUND: The interpretation of trial results can be helped by understanding how generalisable they are to the target population for which inferences are intended. INTERVAL, a large pragmatic randomised trial of blood donors in England, is assessing the effectiveness and safety of reducing inter-donation intervals. The trial recruited mainly from the blood service's static centres, which collect only about 10 % of whole-blood donations. Hence, the extent to which the trial's participants are representative of the general blood donor population is uncertain. We compare these groups in detail. METHODS: We present the CONSORT flowchart from participant invitation to randomisation in INTERVAL. We compare the characteristics of those eligible and consenting to participate in INTERVAL with the general donor population, using the national blood supply 'PULSE' database for the period of recruitment. We compare the characteristics of specific groups of trial participants recruited from different sources, as well as those who were randomised versus those not randomised. RESULTS: From a total of 540,459 invitations, 48,725 donors were eligible and consented to participate in INTERVAL. The proportion of such donors varied from 1-22 % depending on the source of recruitment. The characteristics of those consenting were similar to those of the general population of 1.3 million donors in terms of ethnicity, blood group distribution and recent deferral rates from blood donation due to low haemoglobin. However, INTERVAL participants included more men (50 % versus 44 %), were slightly older (mean age 43.1 versus 42.3 years), included fewer new donors (3 % versus 22 %) and had given more donations over the previous 2 years (mean 3.3 versus 2.2) than the general donor population. Of the consenting participants, 45,263 (93 %) donors were randomised. Compared to those not randomised, the randomised donors showed qualitatively similar differences to those described above. CONCLUSIONS: There was broad similarity of participants in INTERVAL with the general blood donor population of England, notwithstanding some differences in age, sex and donation history. Any heterogeneity of the trial's results according to these characteristics will need to be studied to ensure its generalisability to the general donor population. TRIAL REGISTRATION: Current Controlled Trials ISRCTN24760606 . Registered on 25 January 2012.The trial is funded by NHS Blood and Transplant. The trial’s coordinating centre at the Department of Public Health and Primary Care at the University of Cambridge has received core support from the UK Medical Research Council, the British Heart Foundation and the UK National Institute of Health Research (Cambridge Biomedical Research Centre). Investigators at the University of Oxford have been supported by the Research and Development Programme of NHSBT, the NHSBT Howard Ostin Trust Fund, the UK National Institute of Health Research (Oxford Biomedical Research Centre) through the programme grant NIHR-RP-PG-0310-1004 and the Oxford Biomedical Research Centre.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13063-016-1579-