HOW PHYSICIAN LEADERS CAN SUCCESSFULLY RESOLVE TEAM CONFLICTS.

Examine how physician leaders can become more knowledgeable about assessing the nature of health care team conflicts and intervening with teams to improve their collaboration skills.

IL-4 regulates Bim expression and promotes B cell maturation in synergy with BAFF conferring resistance to cell death at negative selection checkpoints.

IL-4 plays an essential role in the activation of mature B cells, but less is known about the role of IL-4 in B cell maturation and tolerance checkpoints. In this study, we analyzed the effect of IL-4 on in vitro B cell maturation, from immature to transitional stages, and its influence on BCR-mediated negative selection. Starting either from purified CD19(+)IgM(-) B cell precursors, or sorted bone marrow immature (B220(low)IgM(low)CD23(-)) and transitional (B220(int)IgM(high)CD23(-)) B cells from C57BL/6 mice, we compared the maturation effects of IL-4 and BAFF. We found that IL-4 stimulated the generation of CD23(+) transitional B cells from CD23(-) B cells, and this effect was comparable to BAFF. IL-4 showed a unique protective effect against anti-IgM apoptotic signals on transitional B cell checkpoint, not observed with BAFF. IL-4 and BAFF strongly synergized to promote B cell maturation, and IL-4 also rendered it refractory to BCR-mediated cell death. IL-4 blocked upregulation of proapoptotic Bim protein levels induced by BCR crosslinking, suggesting that diminished levels of intracellular Bim promote protection to BCR-induced cell death. Evidence was obtained indicating that downmodulation of Bim by IL-4 occurred in a posttranscriptional manner. Consistent with data obtained in vitro, IL-4 in vivo was able to inhibit Bim upregulation and prevent cell death. These results contribute to the understanding of the role of IL-4 in B lymphocyte physiology, unveiling a previously undescribed activity of this cytokine on the maturation of B cells, which could have important implications on the breaking of B cell central tolerance in autoimmunity.

The introduction of anti-HTLV testing of blood donations and the risk of transfusion-transmitted HTLV, UK: 2002-2006.

The objectives of the study were to describe the introduction of testing blood donations for antibodies to human T-cell lymphotropic virus (anti-HTLV) and to determine the risk of HTLV potentially infectious donations entering the UK blood supply. The rationale for testing was based on (i) evidence of transmission through transfusion in the UK, (ii) the serious nature of HTLV I-associated morbidity and (iii) evidence of infection in UK blood donors. From mid-2002, all blood donations made at UK blood centres were tested in pooled samples using Abbott-Murex HTLV I/II GE 80/81 enzyme immunoassay (EIA). Surveillance data were used to calculate the incidence and prevalence of anti-HTLV and derive estimates of risk. Between August 2002 and December 2006, 106 donations were confirmed positive for anti-HTLV (95 anti-HTLV I and 11 anti-HTLV II). Prevalence was 10-fold higher among donations from new donors than repeat (4.0 and 0.42 per 100 000 donations), and only one repeat donor had evidence of seroconversion. The risk of an HTLV I potentially infectious donation entering the UK blood supply was estimated at 0.11 per million donations (95% confidence interval 0.06 to 0.18). The current very low observed incidence and prevalence among blood donors reflect the very low estimated risk of an HTLV I-positive donation entering the UK blood supply. A change in either the epidemiology of HTLV in UK blood donors or the length of the window period of the test should prompt further review of the risk and a reassessment of anti-HTLV testing in the UK.

Improvement in the performance of HIV screening kits.

SUMMARY: The aim of this study was to assess the performance of HIV screening kits introduced over a 12-year period. HIV kits used by the National Blood Service (NBS) were assessed in the context of other HIV kits employed by diagnostic and reference laboratories. Thirty-three HIV screening kits were assessed and 13 had the potential to be used by the NBS. Specimens applied to NBS evaluations included 2000 HIV-negative specimens collected from blood donors, 200 HIV-positive specimens and 21 seroconversion panels, with larger numbers applied to the latter two categories prior to implementation of Communauté Européennes (CE) marking. The 33 HIV kits gave repeat reactive rates, based on HIV-negative specimens, of between 0% and 0.8% (and between 0% and 0.2% for kits relevant to the NBS). When examined for diagnostic sensitivity, the 33 kits gave sensitivities between 99.78% and 100%. Kits relevant to NBS gave sensitivities of 100% except one kit, which failed to detect one anti-HIV-2-positive specimen. Twenty-six kits were compared for detection of primary HIV infection. Of these, the 10 combined HIV antigen/antibody kits examined were more sensitive than other formats and have been exclusively adopted by NBS where operational considerations allow. Their added seroconversion sensitivity makes them the screening method of choice for populations at increased risk, e.g. in sexually transmitted infection (STI) clinics. The regular review of evaluation results has demonstrated a continuing improvement over time in the performance of HIV screening kits and contributed to advances in blood safety.

Acute effects of haemodialysis on biochemical modulators of endothelial function.

OBJECTIVES: To assess the acute effects of haemodialysis (HD) on biochemical factors modulating endothelial function. SETTING: Academic medical centre. SUBJECTS: Forty patients (age 63.5 +/- 2.2 years, mean +/- SEM) undergoing HD. INTERVENTIONS: Folic acid (F), homocysteine (tHcy), asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (CRP) and malondialdehyde (MDA) were measured pre-HD, 1 h after commencing HD and within the last hour of HD (end-HD). Endothelium-dependent and -independent vasodilatation were measured by applanation tonometry (changes in augmentation index, AIx, postinhaled salbutamol and postsublingual nitroglycerin) in conjunction with biochemical measurements. RESULTS: Marked reductions in serum F (616 +/- 73 vs. 273 +/- 30 nmol L(-1), P < 0.001), tHcy (16.3 +/- 0.7 vs. 11.2 +/- 0.5 micromol L(-1), P < 0.001) and ADMA (0.64 +/- 0.02 vs. 0.47 +/- 0.02 micromol L(-1), P < 0.001) occurred end-HD, whereas CRP and MDA levels did not significantly change. There was no significant change in endothelium-dependent vasodilatation, whereas endothelium-independent vasodilatation improved end-HD (-23.1 +/- 1.9 vs. -17.3 +/- 1.3%, P = 0.018). Regression analysis showed that both higher ADMA (P = 0.029) and lower F levels (P = 0.040) end-HD were determinants of reduced endothelium-dependent vasodilatation end-HD (R(2) = 0.23). CONCLUSIONS: HD is associated with significant reductions in F, tHcy and ADMA serum concentrations. The lack of significant effects of HD on endothelium-dependent vasodilatation could be secondary to the concomitant loss of factors either enhancing (F) or impairing (ADMA) endothelial function.

Increase in recently acquired syphilis infections in English, Welsh and Northern Irish blood donors.

BACKGROUND AND OBJECTIVES: Syphilis can be transmitted by blood. We describe syphilis infections detected in blood donors and investigate the epidemiology of syphilis in English, Welsh and Northern Irish blood donors. MATERIALS AND METHODS: This article analyses routine surveillance data regarding syphilis infections in blood donors from England, Wales and Northern Ireland between 1998 and 2004. Infections are classified as recently acquired or past syphilis and donor characteristics and trends examined. RESULTS: A total of 518 syphilis-infected donors were identified; 40 had recently acquired infection and 407 had past syphilis (71 were unclassified). Thirteen times more recently acquired syphilis infections were identified among people who donated between 2002 and 2004 compared to 1998 to 2001. Young, white and regular donors were most likely to have recently acquired syphilis infections. Heterosexual sex was the main risk exposure identified overall; in contrast, the greatest proportion of recently acquired infections were in men who have sex with men. CONCLUSION: The increase in recently acquired syphilis, although low, indicates that risky sexual behaviours are increasing in the blood donor population, with implications for the microbiological safety of blood. Continued vigilance is required by blood services as the risk of syphilis increases in the general population.

Donors whose blood reacts falsely positive in transfusion microbiology screening assays need not be lost to transfusion.

Donations that repeatedly react in transfusion microbiology screening assays are usually discarded; with appropriate confirmatory testing on the index and on follow-up samples, the great majority of these can be shown to be falsely positive. Under carefully controlled conditions, with secure information transfer, these donations, although still reactive in the primary screening assays, can be made available for clinical use after testing and obtaining negative results with alternative assays from a list of assays evaluated as suitable for the release of blood donations. We will describe a generic algorithm that can be applied to all markers.

Results of an Aboriginal community-based renal disease management program incorporating point of care testing for urine albumin:creatinine ratio.

INTRODUCTION: There has been a significant increase in the burden of renal disease among Aboriginal Australians over the past 15 years. Urine albumin:creatinine ratio (ACR) is a well-established marker of microalbuminuria and can be conveniently performed on the DCA 2000 point-of-care testing (POCT) analyser (Bayer Australia; Melbourne, VIC, Australia) with an on-site result available in 7 min. The application of the urine ACR POCT for renal disease risk assessment was pioneered by our group in the Umoona Kidney Project. This article describes the results of the management arm of the Umoona Kidney Project, which used point-of-care urine ACR testing for the first time within a management framework to monitor albuminuria in patients at highest risk of renal disease. The article also examines the analytical quality of POCT results and overall community acceptance of the Umoona Kidney Project. METHODS: Adults clinically assessed by Flinders Medical Centre renal specialists as being at greatest risk for renal disease were offered the ACE inhibitor (ACEI) perindopril on a voluntary basis. Selected renal markers, including POCT urine ACR (conducted on-site by Umoona's Aboriginal health worker team), plasma electrolytes, urea, creatinine, calculated glomerular filtration rate and blood pressure were measured six monthly. Regular quality control testing was undertaken to monitor the analytical performance of the POCT analyser. A culturally appropriate questionnaire was designed and implemented to assess community satisfaction with the project. RESULTS: In all, 231 patient management consultations were conducted over a two year period, with over 70% of patients having four or more (up to a maximum of eight) consultations; 35 patients (mean age 49.2 [+/-2.3] years, 54% males) participated voluntarily in the management arm. All were overtly hypertensive, hypertensive with other risk factors or had diabetes. The renal status of these patients was followed for a mean of 63 +/- 4.5 weeks. In total, 111 POCT urine ACR tests were performed for patient management (mean 3.2 tests per patient). There was no significant difference in POCT urine ACR in the study period with a median (and inter-quartile range) of 5.7 mg/mmol (1.2-15.2) pre-ACEI and 4.3 mg/mmol (1.3-16.7) post-ACEI treatment (p = 0.50, Wilcoxon signed ranks test). The calculated glomerular filtration rate altered from 110 to 118 mL/min (p = 0.019, paired t-test). There was no change in the group plasma potassium, urea and creatinine. Collectively these results indicate a stabilisation in renal function among the management group. Blood pressure (both lying and standing) fell significantly in the study period. The imprecision for urine ACR quality control POCT conducted during the management program was within nationally and internationally accepted precision goals for urine albumin, creatinine and ACR. Fifty community members completed the satisfaction questionnaire. Three-quarters of respondents felt there were no cultural barriers in providing a urine sample for urine ACR POCT. CONCLUSIONS: The management arm of the Umoona Kidney Project was effective in stabilising the renal function and improving the blood pressure of community members identified to be at greatest risk of kidney disease. POCT urine ACR testing can be utilised, not only for community risk assessment, but also for patient management. The Umoona Kidney Project was well accepted by the health service and community members.

Pall eBDS: an enhanced bacterial detection system for screening platelet concentrates.

Bacterial contamination of blood components remains a significant problem in transfusion medicine. The Pall enhanced bacterial detection system (Pall eBDS) detects the presence of bacteria in leucodepleted platelet concentrates by measuring the reduction of oxygen in the sample, due to aerobic bacterial growth. Pooled platelet concentrates were spiked at 10 cfu mL(-1) with 10 organisms (one species per bag). Pall eBDS pouches were inoculated with the spiked platelet concentrates. After 24 and 30 h of incubation, the oxygen level was measured. A further set of pouches were taken from the inoculated platelet concentrates at 24 h. Incubation and reading intervals were as for the initial set of pouches. A sensitivity study was also performed comparing the Pall eBDS with the BacT/ALERT system. Spiking at 10 cfu mL(-1) and immediately sampling into Pall eBDS pouches resulted in 97.6 and 100% detection after an incubation period of 24 and 30 h, respectively. After 24 h of incubation of the spiked platelet concentrates and then sampling into Pall eBDS pouches, 99.1% detection was obtained after incubation for both 24 and 30 h. The sensitivity of the Pall eBDS and BacT/ALERT is similar and in the order of 1 cfu mL(-1). Implementation of either BacT/ALERT or Pall eBDS for routine screening of platelet concentrates has the potential to further increase the safety of the blood supply.

Documented cases of post-transfusion malaria occurring in England: a review in relation to current and proposed donor-selection guidelines.

BACKGROUND AND OBJECTIVES: Although uncommon, five cases of transfusion-transmitted malaria have been documented in England over the last 20 years. With the reappearance onto the market of high-quality malaria antibody assays, and by utilizing the results of analysis of these five cases, it has been possible to review the donor malaria-deferral guidelines. MATERIALS AND METHODS: Details of the five cases of post-transfusion malaria were reviewed against the proposed new donor-deferral guidelines for malaria. RESULTS: Three of the five cases of post-transfusion malaria were directly attributable to the deferral guidelines, allowing infectious donors to be bled. CONCLUSIONS: The proposed new guidelines will prevent further cases of transmission from semi-immune individuals.

Use of a solid-phase fluorescent cytometric technique for the detection of bacteria in platelet concentrates.

Blood services worldwide are now striving to reduce the risk of transmission of bacteria by transfusion. The BacT/ALERT microbial detection system (bioMerieux, Basingstoke, Hants, UK) is currently regarded as the 'gold standard' for bacterial screening of platelet concentrates. The BacT/ALERT is a culture system and will not generate an 'instant' (within 2 h) determination. We report on the Scansystem (Hemosystem, Marseille, France), a solid-phase fluorescent cytometric technique, which enables the rapid detection of bacteria (within 90 min) in platelet concentrates. The study was performed in two parts - one involving the routine screening of platelet concentrates and the other determining the sensitivity of the system. In both arms of the study, the BacT/ALERT was used for comparative purposes. In total, 900 platelet concentrates were screened (63 apheresis and 837 buffy coat pooled). No bacteria were detected in any of the platelet concentrates tested by means of either the Scansystem or the BacT/ALERT. The sensitivity of the Scansystem was in the order of 10(3) cfu mL(-1). Escherichia coli and Staphylococcus aureus were detected by using the Scansystem at 1 cfu mL(-1). The BacT/ALERT detected all organisms tested (n = 6) at 1 cfu mL(-1). The Scansystem offers a sensitive alternative technology to bacterial culture, with the benefit of a rapid test time.

A novel method for the detection of bacteria in platelet concentrates utilizing oxygen consumption as a marker for bacterial growth.

Bacterial transfusion-transmission remains a significant problem in transfusion medicine. Diversion and improved donor arm disinfection has been introduced by blood services to reduce bacterial transmissions. These interventions are not 100% effective and, therefore, there is still a requirement to screen blood donations, particularly platelet concentrates which are responsible for the majority of transmissions. Pall BDS, a novel bacterial testing system, detects the presence of bacteria in platelet concentrates by measuring the reduction in oxygen content associated with bacterial growth. Buffy coat-derived pooled platelet concentrates were spiked with 12 aerobic and two anaerobic organisms (one species per bag, n = 10) at 100-700 cfu mL(-1). Samples were taken into Pall BDS sample pouches and incubated for 0, 24, 30 and 48 h. An initial incubation was undertaken at 35 degrees C for 24 h and subsequent incubation was at 22 degrees C. At the end of the incubation period the oxygen content in the Pall BDS pouches was measured using a gas analyser. An oxygen content less than or equal to 19.5% was deemed to be positive. Pall BDS pouches tested positive in 80, 94 and 98% units spiked with aerobic bacteria at 24, 30 and 48 h, respectively. Anaerobic bacteria were not detected by the system. Positive BDS pouches contained 10(6) cfu mL(-1) or greater. The system was simple and easy to perform. Pall BDS has a closed sampling system which prevents exogenous contamination. This initial study indicates that the Pall BDS offers a practicable system for detecting bacteria present in leucodepleted platelet concentrates.

Relative values of the interventions of diversion and improved donor-arm disinfection to reduce the bacterial risk from blood transfusion.

BACKGROUND AND OBJECTIVES: The aim of this study was to demonstrate the efficiency of diverting the initial 20-ml donation from the collection bag and of an improved donor-arm disinfection procedure in reducing bacterial contamination in blood. MATERIALS AND METHODS: Donations were collected in bags specially manufactured for the study. These bags incorporated two satellite pouches into each of which 20 ml of blood was collected. Blood initially flowed into sample pouch P1, representing a diversion pouch. Pouch P2 was then filled with 20 ml of blood, which allowed us to sample the collection bag after diversion was complete. Blood then flowed into the standard collection bag. The contents of the pouches were aerobically and anaerobically cultured on the BacT/ALERT automated culture system for 7 days. Two procedures were investigated in the study (each involving 1409 blood donations): one analysed the current disinfection procedure; and the other analysed an improved donor-arm disinfection procedure. RESULTS: The use of diversion alone resulted in a 47% reduction in contamination, and improved donor-arm disinfection alone resulted in a 57% reduction in contamination. Diversion plus improved donor-arm disinfection produced a predicted 77% reduction in contamination. CONCLUSIONS: The study validates diversion and an improved donor-arm disinfection procedure. In combination, these two interventions produced a substantial reduction in contamination. These procedures are to be introduced by the English National Blood Service to enhance the safety of the blood supply.

Estimation of the risk of hepatitis B virus, hepatitis C virus and human immunodeficiency virus infectious donations entering the blood supply in England, 1993-2001.

BACKGROUND AND OBJECTIVES: The frequency of hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infectious donations entering the blood supply in England is too low to monitor using observational studies. The expected frequency of infectious donations can be estimated and these estimates may be used to contribute to monitoring of blood safety and used in the design of strategies to decrease the risk of transfusion-transmitted infections. MATERIALS AND METHODS: The prevalence and incidence of hepatitis B surface antigen (HBsAg), and antibodies to HCV and HIV (anti-HCV and anti-HIV, respectively) in donors in England, between 1993 and 2001, were used together with data about the length of negative 'window-periods' of current assays for each of these markers and data about test performance, to estimate the number of infectious donations that enter the blood supply. The risks were calculated separately for donations from new donors and from repeat donors, and for the three time periods 1993-95, 1996-98 and 1999-01. RESULTS: The estimated frequency of infectious donations entering the blood supply in England, between 1993 and 2001 was 1 in 260,000 for HBV and 1 in 8 million for HIV. For HCV, the frequency of infectious donations was 1 in 520,000 during 1993-98 and fell to 1 in 30 million during 1999-2001 when all donations were tested for HCV RNA. The frequency of HBV- and HCV-infectious donations entering the blood supply fell over these 9 years: the frequency of HIV-infectious donations remained essentially unchanged. The risk from donations from new donors was found to be approximately sevenfold higher than the risk from donations from repeat donors. CONCLUSIONS: The risks of HBV-, HCV- or HIV-infectious donations entering the blood supply in England are very low, and have decreased since 1993. Although the accuracy of these estimates is imperfect, mainly owing to uncertainty in some assumptions and to small numbers of infections, they provide some quantification of the risk of HBV, HCV or HIV transmission by transfusion, and allow comparison of the magnitude of these risks for each infection and over time. The methods we have used have been developed and improved from previously published methods.

HBV DNA levels and transmission of hepatitis B by health care workers.

BACKGROUND: Laboratory-based study funded by the Research and Development Division of the Department of Health to inform the decision making on guidelines for the conduct of exposure prone procedures (EPPs) by health care workers who are hepatitis B carriers. OBJECTIVES: Define the quantity and nature of hepatitis B virus (HBV) DNA in hepatitis carriers whose serum does not contain hepatitis B e antigen (HBeAg) and in surgeons previously cleared to conduct EPPs who have transmitted HBV to their patients. STUDY DESIGN: Cross-sectional survey using HBV DNA quantification, genotyping and sequencing comparing transmitting surgeons and asymptomatic carriers. RESULTS: HBV DNA could be detected and quantified in 64.5% (136 of 211) of carriers whose serum did not contain HBeAg with a median level 3.6 log(10) copies/ml (range of 5.7 log(10) copies). Pre-core mutation appeared not to affect the HBV DNA level, however, all surgeons carried codon 28 variants and transmitted these variants to their patients. The lowest HBV DNA level in a transmitting surgeon was 4 x 10(4) copies/ml. CONCLUSIONS: Pre-core mutations are common in carriers whose serum does not contain HBeAg and do not specifically identify carriers whose HBV DNA levels are high. It was possible to define a level of virus above which transmission of hepatitis B during conduct of EPPs could not be excluded.

Albuminuria in a remote South Australian Aboriginal community: results of a community-based screening program for renal disease.

INTRODUCTION: The poverty, poor environmental living conditions and poor health standards experienced by Aboriginal Australians in some communities in rural and remote Australia have been described recently as 'fourth world'. For more than a century Aboriginal people have suffered the effects of dispossession of their land; destruction of their traditional culture and values; and exposure to infectious diseases, alcohol and the Western diet that is high in fat and sugar. Collectively these factors have contributed to the prevalence of chronic disease that afflicts Aboriginal people. In particular, renal disease has emerged during the last decade as a major contemporary health problem for Aboriginal Australians. According to the latest age- and sex-adjusted figures, Aboriginal people now have approximately nine-fold the risk of non-Aboriginal Australians of developing end-stage renal disease. In parts of Australia's Northern Territory, where Aboriginal people represent over 20% of the Territory's population, the rates of end-stage renal disease have been described as 'epidemic', reaching 2700 per million in the Tiwi Islands. In response to a request from the Umoona Tjutagku Health Service in mid 1997, the Renal Unit at Flinders Medical Centre, Adelaide, South Australia, formed a partnership with the health service to conduct a renal-disease screening program for adult members of the Umoona Community at Coober Pedy, a town 850 kilometres north of Adelaide. The partnership was later expanded to include screening for children (conducted by the Renal Unit at the Women's and Children's Hospital, Adelaide, South Australia). The community named the program 'The Umoona Kidney Project'. The Umoona community had recently experienced the dislocation of a number of its older people who suffered from advanced renal disease and were undergoing dialysis in a variety of centres in South Australia and the Northern Territory. As a result, the community had suffered social trauma. Consistent with the community's overall holistic approach to healthcare, the community wanted the renal program to provide a focus for community awareness of and knowledge about chronic disease, as well as to complement existing health programs. OBJECTIVES: The study objectives were to identify the prevalence of risk factors for renal disease, notably albuminuria, in adults from a remote Aboriginal community, and to examine the association of albuminuria with other risk factors; to empower Aboriginal health workers to self-manage a sustainable, community-controlled renal health program; and to assess the reliability and cultural acceptability of point-of-care technology for detecting renal disease. METHOD: The study was a three-year cross-sectional voluntary adult screening program (The Umoona Kidney Project). The study was performed as a partnership between the Flinders Medical Centre Renal Unit and the Umoona Tjutagku Health Service, and it involved nephrologists, medical scientists, Aboriginal health workers and clinical nurses. SETTING: Umoona Tjutagku Health Service, 850 km north of Adelaide. PARTICIPANTS: 158 adult members of the Umoona community: 58 males (37%; mean age = 43.8 years, range 23-78) and 100 females (63%; mean age = 39.6 years, range 18-72). MAIN OUTCOME MEASURES: First morning urine albumin : creatinine ratio measured by the Bayer DCA 2000 point-of-care analyser machine (Bayer Australia, Melbourne, Australia); lying and standing blood pressure; random blood glucose; body mass index; urinalysis. RESULTS: The study found that of screened adults, 29/149 (19%, 95% C.I. 13%-27%) had persistent microalbuminuria and 13/149 (9%, 95% C.I. 4%-14%) had persistent macroalbuminuria; 62/148 participants (42%, 95% C.I. 34%-50%) had overt hypertension; 35/145 participants (24%, 95% C.I. 17%-32%) had diabetes; 3 participants were newly diagnosed as having non-insulin dependent diabetes; 96/148 participants (65%, 95% C.I. 57%-73%) were either overweight or obese. Strong correlation was observed between the progression of albuminuria and age, all blood pressure categories, blood glucose, body mass index and an increasing number of risk factors. CONCLUSIONS: The Umoona Kidney Project identified a significant community burden of previously unknown incipient and established renal disease that required addressing via clinical- and community-based interventions. The DCA 2000 was a reliable instrument for detecting albuminuria on-site in the remote clinical location and was well accepted by Aboriginal health workers and community participants.