Quality indicators for the hospital transfusion chain: a national survey conducted in 100 dutch hospitals.

BACKGROUND: The 2011 Dutch Blood Transfusion Guideline for hospitals incorporates seven internal quality indicators for evaluation of the hospital transfusion chain. The indicators aim to measure guideline compliance as shown by the instatement of a hospital transfusion committee and transfusion safety officer (structural indicators), observance of transfusion triggers and mandatory traceability of labile blood components (process indicators). STUDY DESIGN AND METHODS: Two voluntary online surveys were sent to all Dutch hospitals for operational years 2011 and 2012 to assess compliance with the guideline recommendations. RESULTS: Most hospitals had a hospital transfusion committee and had appointed a transfusion safety officer (TSO). In 2012, only 23% of hospitals complied with the recommended minimum of four annual transfusion committee meetings and 8 h/week for the TSO. Compliance with the recommended pretransfusion haemoglobin threshold for RBC transfusion was achieved by 90% of hospitals in over 80% of transfusions; 58% of hospitals measured the pretransfusion platelet count in over 80% of platelet transfusions and 87% of hospitals complied with the legally mandatory traceability of blood components in over 95% of transfusions. CONCLUSION: With the current blood transfusion indicators, it is feasible to monitor aspects of the quality of the hospital transfusion chain and blood transfusion practice and to assess guideline compliance. The results from this study suggest that there are opportunities for significant improvement in blood transfusion practice in the Netherlands. These indicators could potentially be used for national and international benchmarking of blood transfusion practice.

Presence of medication taken by blood donors in plasma for transfusion.

BACKGROUND AND OBJECTIVES: The TRIP national hemovigilance and biovigilance office receives reports on side-effects and incidents associated with transfusion of labile blood products. Anaphylactic reactions accounted for the largest number of serious transfusion reactions in the period 2008-2012. In most cases, no cause is found for these reactions. TRIP data show that anaphylactic reactions occur relatively frequently with transfusion of plasma or platelet concentrates. Data from blood services show that 10% or more of plasma donors regularly use medication which is permitted under donation guidelines. It is conceivable that medication taken by the donor in plasma for transfusion could cause an anaphylactic transfusion reaction in the recipient. This exploratory study investigated the presence of drugs or drug metabolites in donor plasma. MATERIALS AND METHODS: Samples (5 ml) were taken from thawed, quarantine fresh frozen plasma units (FFP) which had to be rejected for transfusion because of leaks or length of time after thawing. The samples were analysed for approximately 1000 drugs and drug metabolites using a toxicological screening method. RESULTS: Eighty-seven samples were analysed. Toxicological screening was positive in fourteen samples (16%). In eleven samples, one substance was found, and in three samples, the presence of two or three drugs was detected. CONCLUSION: After freezing, storage and thawing of fresh FFP, it is possible to detect medication taken by the donor. Further investigation is recommended to analyse whether donors' medication in plasma can be implicated in some cases of allergic or anaphylactic reactions in transfusion recipients.

Variation between hospitals in rates of reported transfusion reactions: is a high reporting rate an indicator of safer transfusion?

BACKGROUND AND OBJECTIVES: It has been suggested that the rate of reported transfusion reactions is positively correlated with safety of the transfusion chain in a hospital. We evaluated this assumption in the Transfusion Reactions in Patients Dutch National Hemovigilance Office database taking reported incorrect blood component transfused as a proxy for unsafe transfusion. METHODS: Reports from 2006 to 2010 and annual numbers of transfused blood components from the 103 hospitals were analysed. The rate of transfusion reactions per 1000 blood components was calculated per hospital. Logistic regression analysis was performed between reporting of at least one incorrect blood component and tertile of transfusion reaction rate. RESULTS: Out of the 103 hospitals, 101 had complete data in some and 93 in all 5years. In all, 72 had reported at least one incorrect blood component transfused; this was associated with blood use level and also with rate of reported transfusion reactions: odds ratio 4·2 (95% confidence interval, 1·3-13·7) in the highest vs. the lowest tertile after adjustment for blood use level. CONCLUSION: Hospitals in the Netherlands which report more transfusion reactions per 1000 units are also more likely to have reported incorrect blood component transfused. The data do not support that hospitals with a higher rate of transfusion reaction reports are safer.

Detection and quantitation of gallid herpesvirus 1 in avian samples by 5' Taq nuclease assay utilizing Minor Groove Binder technology.

A 5' Taq nuclease assay utilizing Minor Groove Binder technology and targeting the thymidine kinase gene of gallid herpesvirus 1 (GaHV-1) was designed and optimized for use in diagnosing avian infectious laryngotracheitis. The assay was specific for GaHV-1 in that it did not react with other avian viral or bacterial pathogens. The detection limit was 1.0x10(-2) median tissue culture infectious dose per reaction or 90 target copies per reaction. Fifteen out of 41 diagnostic samples from sick birds reacted in the assay, five of which produced a typical alphaherpesvirus cytopathic effect (CPE) on chicken kidney (CK) cells. Sequencing, using amplicons generated by a polymerase chain reaction with primers flanking the 5' Taq nuclease amplicon, confirmed the presence of GaHV-1 in six samples (two producing alphaherpesvirus CPE on CK cells, three not producing alphaherpesvirus CPE, and one that was not inoculated onto CK cells). Tracheal swabs taken from 18 healthy broilers did not react in the assay. The ability of the assay to determine viral load in samples was demonstrated. Overall the assay is suitable for the rapid diagnosis of infectious laryngotracheitis.

Lower levels of ADAMTS13 are associated with cardiovascular disease in young patients.

ADAMTS13 may play a role in arterial thrombosis by cleaving the highly active and thrombogenic ultralarge Von Willebrand Factor (VWF) multimers into less active VWF multimers. The aim was to investigate the relationship between plasma levels of ADAMTS13, VWF and genetic variation in the ADAMTS13 gene with cardiovascular disease. We performed a case-control study in 374 patients with a first-ever arterial thrombosis before the age of 45 years in males and 55 years in women. We included 218 patients with coronary heart disease (CHD), 109 patients with ischemic stroke (IS) and 47 patients with peripheral arterial disease (PAD) and 332 healthy population-based controls. ADAMTS13 and VWF levels were measured 1-3 months after the event. ADAMTS13 levels were associated with cardiovascular disease (OR antigen 5.1 (95% CI 3.1-8.5, p<0.001) and OR activity 4.4 (95% CI 2.5-7.5, p<0.001), in the lowest quartiles). VWF levels were associated with cardiovascular disease (OR antigen 2.1 (95% CI 1.3-3.3, p=0.001) and OR activity 2.0 (95% CI 1.3-3.1, p=0.003), in the highest quartile). Patients with combined low ADAMTS13 levels and high VWF levels had an odds ratio of 7.7 (95% CI 3.3-17.7) (p for trend <0.0001). No association was found between genetic variation in the ADAMTS13 gene with levels of ADAMTS13 or with risk of cardiovascular disease. In conclusion, levels of ADAMTS13 and VWF are strongly associated with the risk of cardiovascular disease.

Pasteurella multocida detection by 5' Taq nuclease assay: a new tool for use in diagnosing fowl cholera.

A 5' Taq nuclease assay utilising minor groove binder technology and targeting the 16S rRNA gene was designed to detect Pasteurella multocida (the causative agent of fowl cholera) in swabs collected from poultry. The assay was first evaluated using pure cultures. The assay correctly identified four P. multocida taxonomic type strains, 18 P. multocida serovar reference strains and 40 Australian field isolates (17 from poultry, 11 from pigs and 12 from cattle). Representatives of nine other Pasteurella species, 26 other bacterial species (18 being members of the family Pasteurellaceae) and four poultry virus isolates did not react in the assay. The assay detected a minimum of approximately 10 cfu of P. multocida per reaction. Of 79 poultry swabs submitted to the laboratory for routine bacteriological culture, 17 were positive in the 5' Taq nuclease assay, but only 10 were positive by culture. The other 62 swabs were negative for P. multocida by both 5' Taq nuclease assay and culture. The assay is suitable for use in diagnosing fowl cholera, is more rapid than bacteriological culture, and may also have application in diagnosing P. multocida infections in cattle and pigs.

Cognitive-behavioural therapies and exercise programmes for patients with fibromyalgia: state of the art and future directions.

This review provides an overview of the effects of non-pharmacological treatments for patients with fibromyalgia (FM), including cognitive-behavioural therapy, exercise training programmes, or a combination of the two. After summarising and discussing preliminary evidence of the rationale of non-pharmacological treatment in patients with FM, we reviewed randomised, controlled trials for possible predictors of the success of treatment such as patient and treatment characteristics. In spite of support for their suitability in FM, the effects of non-pharmacological interventions are limited and positive outcomes largely disappear in the long term. However, within the various populations with FM, treatment outcomes showed considerable individual variations. In particular, specific subgroups of patients characterised by relatively high levels of psychological distress seem to benefit most from non-pharmacological interventions. Preliminary evidence of retrospective treatment analyses suggests that the efficacy may be enhanced by offering tailored treatment approaches at an early stage to patients who are at risk of developing chronic physical and psychological impairments.

A tomato homologue of the human protein PIRIN is induced during programmed cell death.

Programmed cell death (PCD), with similarities to animal apoptosis, was induced in tomato suspension cells by the topoisomerase I inhibitor camptothecin. Previously, a differential display screening was performed to isolate genes differentially expressed during camptothecin-induced cell death. As a result, the new tomato gene Le-pirin was isolated, whose mRNA levels dramatically increase during camptothecin-induced PCD. Le-pirin mRNA accumulation is also observed when cell death is triggered by the mycotoxin fumonisin-B1, but not when the suspension cells are treated with stress-related compounds such as ethylene, methyl jasmonate or salicylic acid. The caspase inhibitor Z-Asp-CH2-DCB and the calcium channel blocker LaCl3 effectively delayed whereas ethylene greatly stimulated camptothecin-induced PCD and the accumulation of Le-pirin mRNA. The Le-pirin encoded protein shows 56% identity with the human protein PIRIN, a nuclear factor reported to interact with the human oncogene Bcl-3. Human PIRIN stabilizes the formation of quaternary complexes between Bcl-3, the anti-apoptotic transcription factor NF-kappaB and its DNA target sequences in vitro. The isolation of Le-pirin and its implication in plant PCD provides new clues on the role of putative NF-kappaB-associated pathways in plant defence mechanisms.

Chemical-induced apoptotic cell death in tomato cells: involvement of caspase-like proteases.

A new system to study programmed cell death in plants is described. Tomato (Lycopersicon esculentum Mill.) suspension cells were induced to undergo programmed cell death by treatment with known inducers of apoptosis in mammalian cells. This chemical-induced cell death was accompanied by the characteristic features of apoptosis in animal cells, such as typical changes in nuclear morphology, the fragmentation of the nucleus and DNA fragmentation. In search of processes involved in plant apoptotic cell death, specific enzyme inhibitors were tested for cell-death-inhibiting activity. Our results showed that proteolysis plays a crucial role in apoptosis in plants. Furthermore, caspase-specific peptide inhibitors were found to be potent inhibitors of the chemical-induced cell death in tomato cells, indicating that, as in animal systems, caspase-like proteases are involved in the apoptotic cell death pathway in plants.

A clinical and serological comparison of group A versus non-group A streptococcal reactive arthritis and throat culture negative cases of post-streptococcal reactive arthritis.

OBJECTIVE: To identify clinical and serological differences of patients with reactive arthritis after infection with Lancefield group A beta-haemolytic streptococci (GAS), compared with non-group A-that is, group C or G streptococci (NGAS:GCS/GGS), and a group of culture negative or unidentified streptococci (GUS). METHODS: A prospective study of consecutive patients with reactive arthritis after serologically or culture confirmed infection with beta-haemolytic streptococci, presenting to the outpatient department of rheumatology from January 1992 until January 1998. Alternative causes for reactive arthritis were excluded. Main outcome measures were clinical and serological characteristics including antistreptolysine-O (ASO) and antideoxyribonuclease-B (antiDNase-B) antibody titres. RESULTS: 41 patients (female/male ratio 22/19; mean (SD) age 38 (13) years) with reactive arthritis were included. Culture of throat swab was positive in 13 cases (32%): 6 (15%) GAS, 7 NGAS (17%), that is, 5 (12%) GCS, 2 (5%) GGS. In 28 cases throat culture remained negative resulting in a group of unidentified streptococci; antibiotic pre-treatment had been given by the general practitioner in 18 cases (64%). Arthritis was non-migratory, the number of arthritic joints in GAS and NGAS was similar, whereas in NGAS patients fewer joints were involved than in GUS: mean (SEM) 36 swollen joint index: 3.3 (1.0) in NGAS v 5.6 (1.0) in GUS (p<0.005); 28 swollen joint index: 2.9 (1.0) in NGAS v 4.3 (0.8) in GUS (p<0.05). Extra-articular manifestations-that is, erythema nodosum/ multiforme, AV conduction block or hepatitis-were observed after GAS or GUS infection, but not after NGAS infection. ASO and/or antiDNase-B rose significantly in all patients. The maximal titres for ASO and antiDNase-B in 41 PSRA patients were: mean (SEM) 1242 (232) U/l and 890 (100) U/l respectively; the maximal ASO titres were similar in the three groups: mean (SEM) 1125 (185) in GAS, 625 (160) in NGAS (GAS v NGAS: p=0.17), and 1430 (320) U/l in GUS (NGAS v GUS: p=0.10). AntiDNase-B titres were: mean (SEM) 1075 (180) in GAS, 375 (105) in NGAS (GAS v NGAS: p<0.01), and 995 (125) U/l in GUS (NGAS v GUS: p<0.005). ASO: antiDNase-B ratios were: mean (SEM) 0.89 (0.21) in GAS, 2.60 (0.76) in NGAS (GAS v NGAS: p<0.05), and 1.43 (0.28) in GUS (NGAS v GUS: p=0.12). CONCLUSION: Post-streptococcal reactive arthritis occurs not infrequently. Differentiation of PSRA based on the causative streptococcal strain is frequently thwarted by negative throat cultures. Sometimes extra-articular manifestations are present that exclude NGAS as the causative organism. Serologically, lower antiDNase-B titres may be indicative for primary NGAS infection; the ASO/antiDNase-B ratio may be of additive value for differentiation in cases of a negative throat culture: the higher ASO/antiDNase-B ratios suggesting primary NGAS infection. In reactive arthritis, serological monitoring consisting of a simultaneous titration of antiDNase-B and ASO, seems to be of clinical importance to trace GAS induced cases, especially when throat cultures remain negative.

Post-streptococcal reactive arthritis: a clinical and serological description, revealing its distinction from acute rheumatic fever.

OBJECTIVE: To follow-up prospectively patients with arthritis after infection with beta-haemolytic streptococci of Lancefield group A (beta HSA), with emphasis on clinical characteristics and serological features. We additionally investigated whether these patients, though often fulfilling the Jones' criteria for acute rheumatic fever (ARF), had a disease with clinical characteristics different from ARF. DESIGN: We performed a systematic prospective observational study of consecutive patients at a Dutch Outpatient Clinic and Department of Rheumatology, with arthritis after throat infection with beta HSA presenting to rheumatologist or internist from September 1992 until September 1996. Main outcome measures were clinical and biochemical characteristics with special reference to carditis. RESULTS: A total of 23 patients (21 Dutch, two Turkish; female/male ratio 15/8; mean (SD) age 42 (14) years) with predominantly non-migratory arthritis were included. A positive throat swab culture was obtained in 17%. All patients showed a significant rise of antistreptolysine-O (ASO; normal < 200 i.u. mL-1) and antideoxyribonuclease-B (anti-DNase-B; normal < 200 i.u. mL-1) titre. The mean (SEM) maximal ASO was 1305 (195) i.u. mL-1, and anti-DNase-B titre 980 (115) i.u. mL-1. Arthritis was present in mean (SEM) 5.4 (0.9) joints: 2.2 (0.7) small, 3.2 (0.4) larger joints. The arthritis was monarticular in 23% of the patients, oligoarticular in 35%, and polyarticular in 43%. Skin abnormalities were present in 12 patients: erythema nodosum in seven patients (30%), and erythema multiforme in five patients (22%). A transient cholestatic hepatitis was found in four patients (17%). In two patients a transient first-degree conduction block was found; however, neither echocardiography nor clinical course supported carditis. All patients were advised to receive monthly penicillin prophylaxis during a period of 2 years. Two patients refused to follow medical advice: in one a non-migratory arthritis recurred 15 months after the first episode of arthritis. CONCLUSION: Commonly, arthritis secondary to beta HSA infection in the Netherlands, a prosperous West-European country with State Welfare, is not accompanied by carditis, contrary to literature on classical ARF. Other factors discriminating it from ARF are the age of onset, the non-migratory character of the arthritis, the high frequency of erythema nodosum and multiforme, as well as the presence of transient hepatitis. As arthritis is the hallmark of this syndrome, post-streptococcal reactive arthritis (PSRA) is the most proper name for this disease entity. Whether penicillin profylaxis is needed in PSRA, as it is in ARF, warrants further prospective investigation.

Reactive arthritis associated with group C and group G beta-hemolytic streptococci.

OBJECTIVE: Group A beta-hemolytic streptococci (GAS) are known to be capable of evoking sterile arthritis. Reactive arthritis (ReA) has been reported sporadically following primary infection with group C and group G beta-hemolytic streptococci (GCS, GGS). We prospectively studied 4 cases of ReA secondary to throat infection with GCS and GGS. METHODS: Four patients with arthritis secondary to throat infection were seen. Three patients were Dutch, one was Indonesian; female/male ratio was 1/3; mean age was 30 years (range 18-46). Diagnostic evaluation included culture of throat swab and serological screening. RESULTS: All patients presented with a nonmigratory asymmetrical arthritis: monoarthritis in one patient, oligoarthritis in 3. Culture of throat swab was positive in all. Antistreptolysin-O (ASO) titer rose significantly in 2 patients, and anti-DNase-B rose in 2 patients. ASO was maximal (mean 1000 U/ml; range 890-1110) and anti-DNase-B was 395 U/ml (range 290-500). Treatment consisted of feneticillin for 5 days; nonsteroidal antiinflammatory drugs were prescribed on demand. All patients recovered fully in 3 to 12 weeks. CONCLUSION: These cases provide evidence of a benign non-group A streptococcal ReA, i.e., secondary to GCS or GGS. The presence of the organism in the throat along with the elevation of antibody to streptococcal products is important for the diagnosis of GCS/GGS associated ReA. A positive throat culture is needed for differentiation from GAS associated poststreptococcal ReA, because prophylactic measures are effective only in GAS associated sequelae, but not in GCS/GGS associated ReA.

The ipiO gene of Phytophthora infestans is highly expressed in invading hyphae during infection.

The expression of the in planta-induced gene ipiO of the potato late blight pathogen Phytophthora infestans was analyzed during various developmental stages of its life cycle. ipiO mRNA was detected in zoospores, cysts, germinating cysts, and young mycelia, but not in sporangia or in old mycelia grown in vitro. ipiO is not only expressed in stages prior to infection but also during colonization of potato and tomato leaves. In disease lesions, ipiO mRNA was detected in the water-soaked area and the healthy-looking plant tissue surrounding it. In contrast, ipiO mRNA was not found in necrotized tissue or in sporulating areas of a lesion. To determine more precisely the location and time of ipiO gene expression in planta, cytological assays were performed using a P. infestans transformant expressing a transcriptional fusion between the ipiO1 promoter and the beta-glucuronidase (GUS) reporter gene. GUS staining was found specifically in the subapical and vacuolated area of tips of invading hyphae. The histochemical GUS assays demonstrate that ipiO is expressed during biotrophic stages of the disease cycle.

Combination of sulphasalazine and methotrexate versus the single components in early rheumatoid arthritis: a randomized, controlled, double-blind, 52 week clinical trial.

To compare the efficacy of sulphasalazine, methotrexate, and the combination of both in patients with early rheumatoid arthritis (RA), not treated with disease-modifying anti-rheumatic drugs previously, we conducted a double-blind, double-dummy, controlled, clinical trial. One hundred and five patients with active, early RA, rheumatoid factor and/or HLA DR1/4 positive were randomized between sulphasalazine (SSZ) 2000 (maximum 3000) mg daily, or methotrexate (MTX) 7.5 (maximum 15) mg weekly, or the combination (COMBI) of both, and were followed up by a single observer for 52 weeks. The mean change over time per patient, including all visits, in Disease Activity Score (DAS) was: SSZ: -1.6 (95% CI -2.0 to -1.2); MTX: -1.7 (-2.0 to -1.4); COMBI: -1.9 (-2.2 to -1.6); the difference week 0-week 52 (SSZ, MTX, COMBI respectively); DAS: -1.8, -2.0, -2.3, Ritchie articular index: -9.2, -9.5, -10.6, swollen joints: -9.2, -12.4, -14.3, erythrocyte sedimentation rate: -17, -21, -28. Nausea occurred significantly more in the COMBI group. The numbers of drop-outs due to toxicity were SSZ 9, MTX 2, COMBI 5. In conclusion, there were no significant differences in efficacy between combination and single therapy, only a modest trend favouring COMBI. The results of MTX and SSZ were very comparable. Nausea occurred more often in the COMBI group: the number of withdrawals due to adverse events did not differ significantly.

A gene encoding a protein elicitor of Phytophthora infestans is down-regulated during infection of potato.

Most species of the genus Phytophthora produce 10-kDa extracellular protein elicitors, collectively termed elicitins. Elicitins induce hypersensitive response in a restricted number of plants, particularly in the genus Nicotiana within the Solanaceae family. A cDNA encoding INF1, the major secreted elicitin of Phytophthora infestans, a pathogen of solanaceous plants, was isolated and characterized. The expression of the corresponding inf1 gene during the disease cycle of P. infestans was analyzed. inf1 was shown to be expressed in mycelium grown in various culture media, whereas it was not expressed in sporangiospores, zoospores, cysts, and germinating cysts. In planta, during infection of potato, particularly during the biotrophic stage, expression of inf1 was down-regulated compared to in vitro. The highest levels of expression of inf1 were observed in in vitro grown mycelium and in late stages of infection when profuse sporulation and leaf necrosis occur. The potential role of INF1 as an elicitor in interactions between P. infestans and Solanum species was investigated. Nineteen lines, representing nine solanaceous species with various levels of resistance to P. infestans, were tested for response to an Escherichia coli expressed INF1. Within the genus Solanum, resistance to P. infestans did not appear to be mediated by a defense response elicited by INF1. However, INF1 recognition could be a component of nonhost resistance of tobacco to P. infestans.

Characterization of chitinases able to rescue somatic embryos of the temperature-sensitive carrot variant ts 11.

To characterize the acidic endochitinase EP3, able to rescue somatic embryos of the carrot cell line ts11, the enzyme was purified from the medium of wild-type suspension cultures. Peptide sequences, deduced amino acid sequences of corresponding PCR-generated cDNA clones, serological relation and biochemical properties showed that there were at least five closely related chitinases, four of which could be identified as class IV EP3 chitinases with an apparent size of 30 kDa. Two other proteins were identified as a serologically related class I acidic chitinase (DcChitI) of 34 kDa, and a serologically unrelated 29 kDa class II acidic chitinase (DcChitII), respectively. Additional cDNA sequences, Western and Southern analysis showed the presence of a least two, but possibly more, highly homologous class IV EP3 genes in the carrot genome. Two class IV EP3 chitinases were tested and found to be able to increase the number of ts11 globular embryos formed under non-permissive conditions. One of the class IV EP3 chitinases as well as the class I chitinase DcChitI promoted the transition from globular to heart-stage ts11 embryos. The class II endochitinase and a heterologous class IV chitinase from sugar-beet were not active on ts11. This suggests that there are differences in the specificity of chitinases in terms of their effect on plant somatic embryos.