Accuracy of a history of blood donation from surrogate witnesses: data from the UK TMER study.

Look-back studies of blood transfusion in Creutzfeldt-Jakob disease commonly rely on reported history from surrogate witnesses. Data from the UK Transfusion Medicine Epidemiology Review have been analysed to determine the accuracy of the blood donation history provided by the relatives of cases. Our results show that only a small percentage of cases were found to be registered as donors on UK Blood Service (UKBS) databases when there was no family report of blood donation. In contrast, a history of reported donation was less accurate.

Creutzfeldt-Jakob disease and blood transfusion: updated results of the UK Transfusion Medicine Epidemiology Review Study.

BACKGROUND AND OBJECTIVES: This paper reports the results to 31 May 2015 of an ongoing UK study to look for additional cases of variant Creutzfeldt-Jakob disease (vCJD) transmission by blood transfusion, and to seek evidence whether other subtypes of Creutzfeldt-Jakob disease (CJD) may be transmissible via blood components. MATERIALS AND METHODS: All vCJD cases of appropriate age and any sporadic CJD (sCJD) or familial CJD (fCJD) cases with a history of blood donation or transfusion are notified to the UKBS. Donation records are sought and the usage of all donations is determined by look back. Death certificates are obtained for all donors to patients with CJD and recipients of transfused components from patients with CJD who are deceased. RESULTS: The study identified 29 sCJD blood donors, of 370 reported, with transfusion to 211 recipients. Five of these recipients were reported to have died with or of dementia, but were not believed to be cases of CJD. The vCJD arm found 18 vCJD blood donors who had donated blood which was issued for clinical usage, of 24 traced donors from 177 UK vCJD cases. To date, 3 cases of vCJD have occurred in 67 recipients identified in this recipient group, and one recipient had post-mortem confirmation of abnormal prion protein deposition in the spleen (all previously reported). CONCLUSION: The results of the ongoing TMER study show no new cases of transfusion-associated vCJD since 2007 and no evidence of transfusion transmission of sCJD.

Transfusion in children: epidemiology and 10-year survival of transfusion recipients.

OBJECTIVE: To describe the epidemiology of blood transfusion in children: including the incidence of transfusion, the diagnoses leading to transfusion, donor exposure (DE) and post-transfusion survival. STUDY DESIGN AND METHODS: The Epidemiology and Survival of Transfusion Recipients (EASTR) Study was a multi-centre epidemiological study with prospective survival monitoring. Cross-sectional sampling of adult and paediatric transfusion recipients in 29 hospitals was used to select three separate cohorts of red cell (RBC), platelet (PLT) and fresh frozen plasma (FFP) recipients between October 2001 and September 2002. This paper presents the analysis of results for children <16 years. RESULTS: Children <16 years comprised 449 (5%) of the RBC, 362 (9%) of the FFP and 452 (13%) of the PLT recipients. In children 54% of RBC, 63% FFP and 45% PLT recipients were under 1 year of age and 57% RBC, 60% FFP and 52% PLT were male. Median (IQR) DEduring the study year was 3(2-8); 5(2-13) and 11(6-21) in the RBC, FFP and PLT cohorts, respectively. A total of 20% of RBC, 31% of FFP and 54% of PLT recipients had been exposed to >10 donors. Perinatal conditions were the commonest indication for transfusion in the RBC (36%) and FFP (44%) cohorts and comprised 31% of the PLT cohort. Medical conditions (48%), predominantly malignancy (33%), were the most frequent indication in the PLT cohort. The 10 year (95% CI) survival rates were 81% (77-85%), 72% (67-76%) and 71% (66-75%)for RBC, FFP and PLT cohorts, respectively. CONCLUSIONS: Around half of paediatric transfusion recipients are under 1 year of age. Exposure to components from multiple donors is common. At least 70% of paediatric recipients are long survivors and are at risk for late complications of transfusion.

Transfusion in adults: 10-year survival of red cell, plasma and platelet recipients following transfusion.

OBJECTIVE: To determine the long-term survival of adult recipients (>16 years) transfused with red blood cells (RBC), platelets (PLT) and fresh frozen plasma (FFP) in England and Wales. STUDY DESIGN AND METHODS: The EASTR study (Epidemiology and Survival of Transfusion Recipients) was a national multi-centre epidemiological study with cross-sectional sampling from 29 representative hospitals in England supplied by NHS Blood and Transplant (NHSBT). Three separate groups of RBC (n = 9142), FFP (n = 4232) and PLT (3584) recipients were sampled over 1 year (1 October 2001-30 September 2002), with prospective survival monitoring for 10 years. This study presents the data for adult recipients (>16 years of age). RESULTS: The median age interquartile range (IQR) of adult transfusion recipients was RBC 70 (54-79), FFP 66 (51-76), PLT 62 (48-72). The 10-year survival for adult RBC, FFP and PLT recipients was highest for RBC recipients at 36% confidence interval (CI 35-37%, n = 8675), compared with 30% for both FFP (CI 29-32%, n = 3849) and PLT (CI 28-30%, n = 3110) recipients. In all groups, post-transfusion survival decreased with age, and a risk-adjusted analysis showed that reason for transfusion, transfusion type (surgical or medical) and cancer diagnosis (presence or absence) were all significantly associated with survival. Older patients with cancer receiving a medical rather than surgical transfusion had the highest hazard of death. CONCLUSION: This study shows that survival following transfusion in England is broadly similar to that reported in other wealthy nations. More than 70% of recipients die within 10 years of transfusion, but long-term survival is common in younger patients (>80% 10-year survival in RBC recipients aged 16-39 years).

Early cryoprecipitate for major haemorrhage in trauma: a randomised controlled feasibility trial.

BACKGROUND: Low fibrinogen (Fg) concentrations in trauma haemorrhage are associated with poorer outcomes. Cryoprecipitate is the standard source for Fg administration in the UK and USA and is often given in the later stages of transfusion therapy. It is not known whether early cryoprecipitate therapy improves clinical outcomes. The primary aim of this feasibility study was to determine whether it was possible to administer cryoprecipitate, within 90 min of admission to hospital. Secondary aims were to evaluate laboratory measures of Fg and clinical outcomes including thrombotic events, organ failure, length of hospital stay and mortality. METHODS: This was an unblinded RCT, conducted at two civilian UK major trauma centres of adult trauma patients (age ≥16 yrs), with active bleeding and requiring activation of the major haemorrhage protocol. Participants were randomised to standard major haemorrhage therapy (STANDARD) (n=22), or to standard haemorrhage therapy plus two early pools of cryoprecipitate (CRYO) (n=21). RESULTS: 85% (95% CI: 69-100%) CRYO participants received cryoprecipitate within 90 min, median time 60 min (IQR: 57-76) compared with 108 min (67-147), CRYO and STANDARD arms respectively (P=0.002). Fg concentrations were higher in the CRYO arm and were maintained above 1.8 g litre(-1) at all time-points during active haemorrhage. All-cause mortality at 28 days was not significantly different (P=0.14). CONCLUSIONS: Early Fg supplementation using cryoprecipitate is feasible in trauma patients. This study supports the need for a definitive RCT to determine the effect of early Fg supplementation on mortality and other clinical outcomes. TRIAL REGISTRY NUMBER: ISRCTN55509212.

Variant CJD and blood transfusion: are there additional cases?

BACKGROUND AND OBJECTIVES: In this study, we compare variant Creutzfeldt-Jakob disease (vCJD) cases definitely linked to blood transfusion, those with a history of blood transfusion in which no donor has developed vCJD and primary cases with no history of blood transfusion. The aim is to determine whether there are any differences in the demographics or clinical phenotype in these groups that might suggest additional cases of transfusion transmission of vCJD. MATERIALS AND METHODS: All cases of vCJD who are old enough to donate blood (i.e. >17 years old) are notified to the UKBTS at diagnosis, regardless of whether they are known to have a blood donation history. A search is then made for donor records and, if found, all components produced and issued to hospitals are identified and their fate determined. Recipient details are then checked against the NCJDRSU register to establish whether there is a match between these individuals and patients who have been diagnosed with vCJD. In the reverse study, attempts are made to trace the donors to all cases reported to have received a blood transfusion and donors' details are checked against the register to determine if any have developed vCJD. RESULTS: Of the 177 cases of vCJD diagnosed in the UK as of 1 February 2014, the TMER study identified 15 cases reported to have received a blood transfusion. Transfusion records were unavailable for 4 of these cases, all pre-1980, and in one other case there was no transfusion recorded in the medical notes. Transfusion records were found for 10 cases. One case transfused at symptom onset was excluded from this analysis. The mean age at onset of symptoms of the remaining nine transfusion recipients (four female and five male) was 42·9 years; 57·6 years in the three known transfusion-transmitted cases and 35·5 years in the six not linked cases. In one of these cases, details of components transfused were unavailable, and the remaining five cases received a total of 116 donor exposures with 112 donors identified, none of whom is known to have developed clinical vCJD. To date, five of the 112 identified donors have died and none was certified as dying of vCJD or any other neurological disorder. Two of the transfusion-transmitted cases did not fulfil diagnostic criteria for probable vCJD during life but were confirmed at post-mortem. Both cases were in the older age range (68 and 74 years, respectively), and neither had a positive MRI brain scan. The remaining cases all fulfilled the criteria for the diagnosis of vCJD in life, but two of these had atypical features and were older than the expected age at onset for vCJD. CONCLUSION: In conclusion, it is possible that one or more of the vCJD cases that received a blood transfusion derived from an individual not known to have vCJD were infected by the blood transfusion. However, the evidence for this is weak, and the absence of a past history of transfusion in most cases of vCJD excludes a large number of unrecognised transfusion-transmitted cases.

A retrospective case note review of deceased recipients of vCJD-implicated blood transfusions.

BACKGROUND: To date, four instances of probable transfusion-transmission of variant Creutzfeldt-Jakob disease (vCJD) infection have been described, and surviving recipients of vCJD-implicated blood components have been informed that they may be 'at risk' of vCJD. Nearly two-thirds of all recipients of vCJD-implicated blood components are deceased, and many died before the vCJD risk was known. The primary aim of this study was to determine retrospectively whether there was evidence that any of the other deceased recipients of vCJD-implicated blood components had any clinical signs or symptoms suggestive of vCJD in life. In addition, pathological material from recipients, stored at the time of surgery or autopsy, was sought to allow testing for evidence of vCJD infection. A secondary aim of the study was to obtain information on invasive healthcare procedures undertaken on recipients following the transfusion to identify the potential for onward transmission of infection. METHODS: A retrospective review of medical case notes of deceased recipients of vCJD-implicated blood components was carried out, and relevant information was extracted. In cases undergoing post-mortem, details of the findings were obtained. RESULTS: The medical case notes of 33 (83%) deceased recipients of vCJD-implicated blood components, not already known to be infected with vCJD, were reviewed. The median age of recipients was 68 years (interquartile range 57-79 years). Almost half (16) were male. The median time from transfusion to death was 175 days (interquartile range 43-701 days). Most (66%) recipients died in hospital. None of the recipients had documented evidence of clinical signs or symptoms suggestive of vCJD. Only two recipients, both of whom died within a year of transfusion, underwent autopsy examination. Neither brain nor peripheral lymphoreticular tissue was available from either recipient, and pathological material was unavailable from any of the other deceased recipients. Almost half of all recipients underwent at least one invasive healthcare procedure post-transfusion. CONCLUSIONS: A retrospective review of the medical case notes of the deceased recipients of vCJD-implicated blood components found no evidence that any further cases expressed clinical signs or symptoms suggestive of vCJD during life, but only four of the recipients survived for more than 5 years post-transfusion.

Variant Creutzfeldt-Jakob disease and exposure to fractionated plasma products.

BACKGROUND: The risk to public health of onward transmission of variant Creutzfeldt-Jakob disease (vCJD) via blood transfusion and plasma product administration is of on-going concern, particularly with the recent reported detection of abnormal prion protein in a person with haemophilia. OBJECTIVES: To describe the history of fractionated plasma product exposure in clinical cases of vCJD in the UK. METHODS: Through examination of records held at the National CJD Surveillance Unit (from relatives, general practices and hospitals). RESULTS: Nine out of 168 UK vCJD cases had a history of receipt of fractionated plasma products on 12 different occasions (1 pre-vCJD risk in 1970, the remaining between 1989-1998). According to the UK CJD Incident Panel risk assessment criteria, 11 were low-risk products and one was low or medium risk. CONCLUSION: It is unlikely that any of the UK vCJD clinical cases to date were infected through exposure to fractionated plasma products. However, the possibility that such transmission may result in vCJD cases in the future cannot be excluded.

The EASTR study: a new approach to determine the reasons for transfusion in epidemiological studies.

Previous studies of blood use have used different methods to obtain and classify transfusion indications. Before undertaking a national study of transfusion recipients, a pilot study was performed over 2 months at two teaching and two district general hospitals to match information from hospital transfusion laboratories with clinical coding data from the hospital's Patients Administration System to determine the indication for transfusion in 2468 recipients. Data analysis revealed major limitations in the conventional use of primary diagnostic International Statistical Classification of Disease and Related Health Problems 10th Revision (ICD-10) or procedure Office of Population, Censuses and Surveys - Classification of Surgical Operations and Procedures - 4th Revision (OPCS-4) codes alone in allocating transfusion indications. A novel algorithm was developed, using both types of code, to select the probable indication for transfusion for each patient. A primary OPCS-4 code was selected for recipients transfused in relation to surgery (43%) and either the primary (36%) or the secondary (12%) ICD-10 code was chosen for recipients transfused for medical reasons. The remaining patients were unclassified. Selected codes were then collated into Epidemiology and Survival of Transfusion Recipients (EASTR) casemix groups (E-CMGs). The most frequent E-CMGs were haematology (15% of recipients), musculoskeletal (14%), digestive system (12%) and cardiac (10%). The haematology E-CMG includes patients with malignant and non-malignant blood disorders and recipients transfused for anaemia where no cause was listed. Recipients undergoing hip and knee replacement and coronary artery bypass grafting are within the musculoskeletal and cardiac E-CMGs. The digestive E-CMG includes recipients transfused for gastrointestinal (GI) bleeds and those undergoing GI surgery. This methodology provides a more useful means of establishing the probable indication for transfusion and arranging recipients into clinically relevant groups.

The EASTR Study: indications for transfusion and estimates of transfusion recipient numbers in hospitals supplied by the National Blood Service.

This study provides data on National Blood Service (NBS) red blood cell (RBC, n = 9142), platelet (PLT, n = 4232) and fresh frozen plasma (FFP, n = 3584) recipients independently sampled by monthly quota from 29 representative hospitals over 12 months in 2001-2002. Hospitals were stratified by size according to total yearly RBC issues. Transfusion indications were chosen from diagnostic and procedural codes, and recipients grouped into Epidemiology and Survival of Transfusion Recipients Case-mix Groups (E-CMGs). The main E-CMGs were digestive [19% of RBC recipients; including 5% gastrointestinal (GI) bleeds and 3% colorectal surgery], musculoskeletal (15%; 12% hip and knee replacement), haematology (13%) and obstetrics and gynaecology (10%). Renal failure, fractured neck of femur, cardiac artery by-pass grafting (CABG) and paediatrics, each accounted for 3-4% recipients. FFP recipients: the main E-CMGs were digestive (21% of FFP recipients; including 7% GI bleeds and 3% colorectal surgery), hepatobiliary (15%; 7% liver disease and 2% liver transplant), cardiac (12%) and paediatrics (9%) The renal, paediatrics, vascular and haematology E-CMGs each had 6-7% of recipients. PLT recipients: the main E-CMGs were haematology (27% of PLT recipients; including 9% lymphoma and 8% acute leukaemia), cardiac (17%), paediatrics (13%), hepatobiliary (10%) and digestive (9%). Back-weighting gave national estimates of 433 000 RBC, 57 500 FFP and 41 500 PLT recipients/year in England and North Wales, median age 69, 64 and 59 years, respectively. Digestive and hepatobiliary indications emerged as the top reason for transfusion in RBC and FFP recipients, and was also a frequent indication in PLT recipients.

Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion.

BACKGROUND: Variant Creutzfeldt-Jakob disease (vCJD) is a novel human prion disease caused by infection with the agent of bovine spongiform encephalopathy (BSE). Epidemiological evidence does not suggest that sporadic CJD is transmitted from person to person via blood transfusion, but this evidence may not apply to vCJD. We aimed to identify whether vCJD is transmissible through blood transfusion. METHODS: The national CJD surveillance unit reported all cases of probable or definite vCJD to the UK blood services, which searched for donation records at blood centres and hospitals. Information on named recipients and donors was provided to the surveillance unit to establish if any matches existed between recipients or donors and the database of cases of vCJD. Recipients were also flagged at the UK Office of National Statistics to establish date and cause of death. FINDINGS: 48 individuals were identified as having received a labile blood component from a total of 15 donors who later became vCJD cases and appeared on the surveillance unit's register. One of these recipients was identified as developing symptoms of vCJD 6.5 years after receiving a transfusion of red cells donated by an individual 3.5 years before the donor developed symptoms of vCJD. INTERPRETATION: Our findings raise the possibility that this infection was transfusion transmitted. Infection in the recipient could have been due to past dietary exposure to the BSE agent. However, the age of the patient was well beyond that of most vCJD cases, and the chance of observing a case of vCJD in a recipient in the absence of transfusion transmitted infection is about 1 in 15000 to 1 in 30000.

Costs and quality of life associated with acute upper gastrointestinal bleeding in the UK: cohort analysis of patients in a cluster randomised trial.

OBJECTIVES: Data on costs associated with acute upper gastrointestinal bleeding (AUGIB) are scarce. We provide estimates of UK healthcare costs, indirect costs and health-related quality of life (HRQoL) for patients presenting to hospital with AUGIB. SETTING: Six UK university hospitals with >20 AUGIB admissions per month, >400 adult beds, 24 h endoscopy, and on-site access to intensive care and surgery. PARTICIPANTS: 936 patients aged ≥18 years, admitted with AUGIB, and enrolled between August 2012 and March 2013 in the TRIGGER trial of AUGIB comparing restrictive versus liberal red blood cell (RBC) transfusion thresholds. PRIMARY AND SECONDARY OUTCOME MEASURES: Healthcare resource use during hospitalisation and postdischarge up to 28  days, unpaid informal care, time away from paid employment and HRQoL using the EuroQol EQ-5D at 28  days were measured prospectively. National unit costs were used to value resource use. Initial in-hospital treatment costs were upscaled to a UK level. RESULTS: Mean initial in-hospital costs were £2458 (SE=£216) per patient. Inpatient bed days, endoscopy and RBC transfusions were key cost drivers. Postdischarge healthcare costs were £391 (£44) per patient. One-third of patients received unpaid informal care and the quarter in paid employment required time away from work. Mean HRQoL for survivors was 0.74. Annual initial inhospital treatment cost for all AUGIB cases in the UK was estimated to be £155.5 million, with exploratory analyses of the incremental costs of treating hospitalised patients developing AUGIB generating figures of between £143 million and £168 million. CONCLUSIONS: AUGIB is a large burden for UK hospitals with inpatient stay, endoscopy and RBC transfusions as the main cost drivers. It is anticipated that this work will enable quantification of the impact of cost reduction strategies in AUGIB and will inform economic analyses of novel or existing interventions for AUGIB. TRIAL REGISTRATION NUMBER: ISRCTN85757829 and NCT02105532.

Conversion of [4-14C]progesterone to androstenedione in vitro by thecal tissue from the ovary of the domestic fowl (Gallus domesticus).

The conversion of [4-14C]progesterone to androstenedione by thecal tissue homogenates from the large yellow follicles of the hen ovary was measured at two periods of the ovulatory cycle after incubation for 1 h in the presence of cofactors. Production of androstenedione by the largest follicle, F1, was reduced significantly 1-2 h before ovulation compared with 15 h before ovulation, whereas production of an unidentified androgen increased. These differences were not observed in the next largest follicles, F2 and F3. Thecal tissue homogenates from all the follicles converted [4-14C]progesterone to 17 alpha-hydroxyprogesterone, androstenedione and testosterone.

Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiological Review study.

BACKGROUND AND OBJECTIVES: This paper reports the results to 1 March 2006 of an ongoing UK study, the Transfusion Medicine Epidemiological Review (TMER), by the National CJD Surveillance Unit (NCJDSU) and the UK Blood Services (UKBS) to determine whether there is any evidence that Creutzfeldt-Jakob disease (CJD), including sporadic CJD (sCJD), familial CJD (fCJD), and variant CJD (vCJD) is transmissible via blood transfusion. MATERIALS AND METHODS: Sporadic CJD and fCJD cases with a history of blood donation or transfusion are notified to UKBS. All vCJD cases aged > 17 years are notified to UKBS on diagnosis. A search for donation records is instigated and the fate of all donations is identified by lookback. For cases with a history of blood transfusion, hospital and UKBS records are searched to identify blood donors. Details of identified recipients and donors are checked against the NCJDSU register to establish if there are any matches. RESULTS: CJD cases with donation history: 18/31 vCJD, 3/93 sCJD, and 3/5 fCJD cases reported as blood donors were confirmed to have donated labile components transfused to 66, 20, and 11 recipients respectively. Two vCJD recipients have appeared on the NCJDSU register as confirmed and probable vCJD cases. The latter developed symptoms of vCJD 6.5 years and 7.8 years respectively after receiving non-leucodepleted red blood cells (RBCs) from two different donors who developed clinical symptoms approximately 40 and 21 months after donating. A third recipient, given RBC donated by a further vCJD case approximately 18 months before onset of clinical symptoms, had abnormal prion protein in lymphoid tissue at post-mortem (5-years post-transfusion) but had no clinical symptoms of vCJD. CJD cases with history of transfusion: Hospital records for 7/11 vCJD and 7/52 sCJD cases included a history of transfusion of labile blood components donated by 125 and 24 donors respectively. Two recipients who developed vCJD were linked to donors who had already appeared on the NCJDSU register as vCJD cases (see above). No further links were established. CONCLUSION: This study has identified three instances of probable transfusion transmission of vCJD infection, including two confirmed clinical cases and one pre- or sub-clinical infection. This study has not provided evidence, to date, of transmission of sCJD or fCJD by blood transfusion, but data on these forms of diseases are limited.

Plasma progesterone concentrations during pregnancy and pseudopregnancy and onset of ovarian activity post partum in indigenous goats in Zimbabwe.

Eight pregnant does were housed individually and fed a hay and concentrate diet throughout pregnancy and lactation. The mean gestation period was 146.7 +/- 3.0 days, with a twinning rate of 75 per cent. Mean body condition scores improved from 2.4 +/- 0.2 to 2.8 +/- 0.2 over the first 80 days of gestation and were maintained at 2.8 until 45 days before kidding. From then until kidding, mean scores fell to 2.2 +/- 0.2. Plasma progesterone concentrations during pregnancy rose significantly from 3.91 +/- 0.51 ng/ml on day 40 to 5.96 +/- 0.51 ng/ml on day 60 (P < 0.05) and remained high until 5 days before kidding. Three pseudopregnant does had similar progesterone profiles to pregnant does over the first 80 days, but the rise around day 35 to 40 was not significant and progesterone concentrations returned gradually to basal levels after day 100. The same 8 does, together with an additional 4 does which had been brought inside 60 to 70 days before kidding, were used to study onset of ovarian activity post partum. The twinning percentage was 83 per cent. Mean body condition score at parturition was 2.2 +/- 0.1. By day 35 post partum, mean condition scores had fallen to 1.9 +/- 0.1, and mean weights from 36.9 +/- 1.9 kg at kidding to 32.1 +/- 2.0 kg. Ovarian cyclicity was resumed just before mean scores and weights started to improve. The mean interval from kidding to onset of oestrous cycles was 97.3 +/- 9.5 days. This coincided with mean time to weaning which was 99.5 +/- 5.5 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of season and housing on ovarian activity of indigenous goats in Zimbabwe.

Progesterone profiles were monitored in goats housed in single (n = 9) or group (n = 14) pens during winter (JJA) and spring (SON). Normal cycles (n = 97) were < or = 30 days. Extended cycles (n = 45) were > 30 days and, except for one cycle with a persistent corpus luteum, had periovulatory periods of 10 to 20 days (n = 29) or averaging 65.1 days in length (n = 15), mostly characterised by recurrent oestrus and/or occasional transient rises in progesterone. The proportion of normal cycles occurring in winter was 87.5% (28/32) and 77.7% (42/54) for goats in single and group pens respectively, falling to 62.5% (15/24) and 37.5% (12/32) respectively in spring. The distribution of normal vs extended cycles according to season was significant (P < 0.05, single; P < 0.001 group pens). Goats housed communally experienced a greater fall in the percentage of normal cycles in spring, possibly due to increased stress associated with group feeding. Within each season, however, housing per se did not influence the distribution of normal vs extended cycles. For normal cycles, Harvey's Analysis of Variance showed that season was significantly associated with length of the periovulatory period (3.99 days (JJA) vs 5.79 days (SON); P < 0.001), oestrus detection rate (87% (JJA) vs 55% (SON); P < 0.01) and oestrus duration (1.94 days (JJA) vs 1.13 days (SON); P < 0.05). In contrast, luteal phase length was not affected by season, but was significantly associated with housing (16.93 days (single pens) vs 18.32 days (group pens); P < 0.01). The reduction in ovarian activity observed in spring may reflect a seasonal reduction in fertility, possibly linked with increasing temperature and photoperiod.

Oestrus in the British white goat: timing of plasma luteinizing hormone surge and changes in behavioural and vaginal traits in relationship to onset of oestrus.

Length of oestrus and timing of the LH surge was measured in six British White does, housed with a vasectomized buck (experiment 1). The following breeding season, pulsatile LH release during the cycle was measured in eight does and the pattern of behavioural and vaginal traits in relation to onset of oestrus (time 0) determined (experiment 2). In experiment 1, the interval to first oestrus after introduction of the buck on 1st October was 10.3 +/- 3.0 days (n = 6) but in experiment 2, when the buck was put in on 1st September, first oestrus occurred after 39.3 +/- 3.4 days in 7/8 does and 7 days in 1/8 does indicating that adequate exposure to short days is needed before the buck can initiate ovarian activity. LH pulse frequency increased from 0-1 pulses/8 h to 3 pulses/8 h after luteolysis, with no change in pulse amplitude, suggesting that progesterone regulates LH pulse frequency. Mean LH values rose from basal to 102.1 +/- 7.8 ng/ml, 12 +/- 1.5 h after the onset of oestrus, which was 16.3 +/- 1.7 h in length. Does sought out the buck and displayed tail wagging, bleating and restlessness from -60 h to +36 h relative to the onset of oestrus (time 0). The incidence of these activities rose at -12 h and peaked at 0 h. Tail wagging, but not bleating or restlessness, also increased in intensity at 0 h, as did the intensity with which the doe actively sought out the buck. Vulval redness and swelling and onset of a clear thin vaginal discharge were first observed 1-2 days before oestrus, becoming maximal on day 0. It was concluded that onset of frequent tail wagging was the most useful trait for detecting onset of oestrus.

Using patient-identifiable data for epidemiological research.

The use of patient-identifiable data in epidemiological research is subject to increasingly complex regulation. This article reports the experience of a research team in setting up the Epidemiology and Survival of Transfusion Recipients (EASTR) study in which patient-identifiable information was needed in order to link data from two sources for analysis and obtain long-term survival patterns of transfusion recipients. The process of establishing the study involved obtaining separate ethical, research and development and data protection approval, including application to the newly formed Patient Information Advisory Group, set up under Section 60 of the Health and Social Care Act, 2001. We describe the high cost in administrative procedures and time now necessary to gain statutory approval before such a study can begin, which has been the result of recent legislation. Issues arising from our experience are discussed.

Solvent/detergent fresh frozen plasma as primary treatment of acute thrombotic thrombocytopenic purpura.

Three patients with acute thrombotic thrombocytopenic purpura (TTP) (one associated with E. coli infection) received as primary treatment pooled fresh frozen plasma (FFP) virus inactivated by the solvent/detergent (SD) method, plus prednisolone. All three patients attained platelet counts of > 50 x 10(9)/l by days 7, 3 and 10, respectively. Serum creatinine became corrected in parallel. Neurological features were slow to resolve in one patient, and developed de novo during plasma infusion in another with rapid reversal once intensive plasma exchange with SDFFP was instituted. All patients are in stable remission > 1 years later. SDFFP was well tolerated with no febrile or other reactions, and all patients remained negative for markers of infection with HIV, hepatitis B and hepatitis C viruses. One patient was positive for antibodies for hepatitis A virus and parvovirus B19 prior to treatment. The other two patients remained antibody negative at the end of therapy.