Junior doctors' perspectives on transfusion education in Australia.

BACKGROUND: Early postgraduate training is a critical period to develop skills and to influence future clinical practice. Little is known about Australian junior doctors' existing transfusion knowledge and its application in patient care. This study explored their transfusion practice education preferences, developed tools to assist their practice and assessed the usefulness of these tools. METHODS: A design-based study was conducted in two phases from April 2016 to March 2017. Phase 1 involved focus group sessions in six hospitals. Transcripts of audio recordings were analysed using thematic analysis. Findings were considered when developing transfusion practice support tools. Phase 2 surveyed junior doctors' response to the tools provided during orientation in five hospitals. Participation was voluntary. RESULTS: Fifty-two junior doctors participated in the focus groups. Their priority was to be able to practice safely, appropriately and confidently. Preferred format for transfusion learning included expert-led face-to-face education; printed tools, for example lanyard cards; and for one app that covers essential aspects of transfusion practice. Adverse events management and practical transfusion prescribing were topics of most importance. Thirty-nine survey respondents found the transfusion practice support tools useful and recommended their use to complement practice. CONCLUSION: There is a need for improved education to ensure best transfusion practice and patient outcomes. Australian junior doctors want immediate, practical, reliable transfusion information from credible sources to support them in practicing safely and confidently. Their educational needs are driven by real-time patient management. Promotion of the available resources and tools provided by the blood sector is important.

Effect of factor VIII concentrate on leucocyte cytokine receptor expression in vitro: relevance to inhibitor formation and tolerance induction.

Inhibitor formation in haemophilia patients receiving factor VIII (FVIII) concentrate is a serious problem requiring tolerance induction therapy. Inhibitor antibody formation is dependent on interactions between leucocyte cytokines with their corresponding receptors. To investigate this we studied the effect of FVIII on cytokine receptor expression using multiparameter flow cytometry and a whole blood stimulation assay. Upregulation of many cytokine receptors was inhibited by plasma-derived FVIII (pdFVIII) in a dose-dependent manner on T cells, B cells and monocytes although interleukin (IL)-4Ralpha and IL-7Ralpha were upregulated on T cells. The decrease in cytokine receptor upregulation on B cells in the presence of pdFVIII, may result in reduced antibody production. Inhibition of CD132 in the presence of pdFVIII may result in immune tolerance in some recipients of pdFVIII. The immunomodulatory effects of pdFVIII were dose and batch dependent, some being more inhibitory than others. The inhibitory effects of prednisolone with pdFVIII, on cytokine receptor upregulation, were additive. Cytokine receptor expression was not altered in the presence of human recombinant FVIII (rFVIII) concentrate. These findings may explain the reports of less frequent inhibitor antibody formation in some recipients of pdFVIII concentrates. The use of pdFVIII, particularly the more inhibitory batches, may be more suitable than rFVIII for tolerance induction protocols. A clinical study needs to be undertaken to determine the significance of these in vitro findings.

Orbital rhabdomyosarcoma: multidisciplinary treatment experience.

Orbital rhabdomyosarcoma (RMS) accounts for 10% of childhood RMS and has a relatively good prognosis of up to 85% 5-year survival. Improved survival has led to increased interest in late effects of treatment. The objective of this study was to review the results of treating orbital RMS with multidisciplinary treatment at Women's and Children's Hospital and Royal Adelaide Hospital with emphasis on late effects of treatment. A retrospective review was carried out of all patients with orbital RMS treated with multidisciplinary treatment including radiation therapy and chemotherapy in the two institutions between 1982 and 2002. A total of five patients (age range 5.5-12 years) satisfied the eligibility requirements. Late effects were significant and included facial bone hypoplasia, cataract formation and growth hormone deficiency. Overall survival was 80% (4/5) with mean follow up of 8 years (range 3-13 years). Given the high cure rates achieved, future treatments must aim to maintain the good results but to reduce the high incidence of late effects of treatment. Standardised rating of late toxicity, long-term follow-up clinics, and implementation of modern radiation techniques (3-D conformal radiotherapy, intensity modulated radiotherapy, proton therapy) for patients with orbital RMS are important to improving outcome.

Allogeneic bone marrow transplant improves outcome for juvenile myelomonocytic leukaemia.

OBJECTIVE: To correlate clinical presentation and therapeutic outcomes in children with a diagnosis of juvenile myelomonocytic leukaemia. METHODS: The medical records of 14 children who fulfilled the International Juvenile Myelomonocytic Leukaemia Working Group Criteria for a diagnosis of juvenile myelomonocytic leukaemia (JMML) presenting to a single institution were reviewed, and their clinical status at September 2000 was documented. RESULTS: The most common presenting features were hepatosplenomegaly and lymphadenopathy. Fifty per cent of cases presented in the first year of life. Nine of 14 patients initially received chemotherapy otherwise used in the treatment of acute myeloid or lymphoblastic leukaemia with no apparent benefit. All six patients who received conditioning therapy with chemotherapy alone, followed by allogeneic bone marrow transplant (BMT), are in complete remission at a median follow-up duration of 12 months (range 5-91 months). Five of six patients surviving post-allogeneic BMT received marrow from an unrelated donor. Only one of seven patients who did not receive BMT survived long-term. CONCLUSION: Children with a diagnosis of JMML should be treated with allogeneic BMT as soon as a suitable donor is found. The role of anti-leukaemic therapy in this disease, prior to BMT, requires further investigation in the context of a multicentre clinical trial.

Pseudomonas aeruginosa infection mimicking erythema annulare centrifugum.

A 3-year-old girl receiving chemotherapy for acute lymphocytic leukaemia developed a rapidly expanding red annular plaque on her thigh, initially without signs of systemic toxicity or local pain. Subsequently she developed Pseudomonas aeruginosa sepsis and purpura at the leading edge of the plaque. Skin biopsy showed an extensive necrotizing vasculitis with numerous Gram-negative bacilli in the blood vessel walls. In immunocompromised individuals, skin biopsy and culture of cutaneous lesions for bacteria and fungi should be considered even in the absence of signs of systemic toxicity or multiple lesions.

Bones, groans and blasts.

A 14-year-old girl presented with the acute onset of gastrointestinal symptoms due to hypercalcaemia. Chest X-ray revealed osteolytic lesions in the ribs which in conjunction with a normal parathyroid hormone level raised the possibility of malignancy. Despite the absence of blast cells in her blood film, the bone marrow biopsy was diagnostic of acute lymphoblastic leukaemia. She responded well to treatment with pamidronate and chemotherapy.

Pediatric heparin-induced thrombocytopenia: management with Danaparoid (orgaran).

Heparin-induced thrombocytopenia is a rare and serious complication of anticoagulation therapy. There remains a paucity of information pertaining to alternative anticoagulation strategies for use during cardiopulmonary bypass concomitant with heparin-induced thrombocytopenia, especially in children. We report the successful treatment of heparin-induced thrombocytopenia and subsequent hemorrhagic complications postoperatively in a 2-year-old child with Danaparoid (orgaran). Emergent conduit revision with cardiopulmonary bypass was required for a thrombosed systemic-venous to pulmonary-arterial connection (completion modified Fontan procedure). Required doses of Danaparoid were consistently twofold that previously reported for adults.

Reticulated platelet counts in the assessment of thrombocytopenic disorders.

Reticulated platelets (RP) are the youngest platelets in the circulation and can be measured by analysing the RNA content of platelets from whole blood or platelet-rich plasma by flow cytometry. Increased RP are indicative of increased production of platelets. Despite the current lack of standardization for the measurement of RP, it is useful in the assessment of patients with ITP by aiding the distinction of these patients from those with decreased platelet production. RP counts also have a role in the assessment of the complicated patient with multiple possible aetiologies for thrombocytopenia. Measurement of the RP count may hold predictive value for marrow recovery following myelosuppressive or myeloablative chemotherapy, and may play a role in monitoring the administration of the various thrombopoietins currently under clinical trial.

Regression of extramedullary haemopoiesis and augmentation of fetal haemoglobin concentration during hydroxyurea therapy in beta thalassaemia.

Hydroxyurea increases fetal haemoglobin in many patients with sickle cell anaemia, but its effectiveness in thalassaemia appears to be less consistent. We describe the response to hydroxyurea in an adult male with homozygous beta thalassaemia, symptomatic paraspinal extramedullary haemopoiesis, bone pain, and progressive tissue iron loading. Prior to therapy with hydroxyurea the circulating haemoglobin (Hb) concentration was 7.0 g/dl and absolute fetal haemoglobin concentration was 5.0 g/dl. Administration of sodium phenylbutyrate had induced no increase in either parameter. Subsequent therapy with hydroxyurea was associated with increases in total haemoglobin to 9.0 g/dl, and in fetal haemoglobin to 7.6 g/dl. Ineffective erythropoiesis was reduced and extramedullary haemopoiesis regressed during therapy.

Reticulated platelet counts in the diagnosis of acute immune thrombocytopenic purpura.

PURPOSE: Bone marrow aspiration is often performed to diagnose childhood acute immune thrombocytopenic purpura (ITP) because no non-invasive investigation to confirm the diagnosis is routinely available. Reticulated platelets (RPs--young platelets characterized by a high RNA content--increase with increased platelet production and may be useful in the diagnosis of ITP. METHODS: To assess the role of RP counts in distinguishing ITP, we compared counts from 15 consecutive patients with ITP with counts from 20 patients with acute lymphoblastic leukemia (ALL), 10 with aplasia, and 27 healthy normal children. Whole blood in edetic acid (EDTA) was labelled with a platelet-specific monoclonal antibody and incubated with thiazole orange (TO). A standard gate was set to achieve a fluorescence value of 1.3 +/- 0.5% for control lyophilized platelets. RESULTS: Patients with ITP had a mean (+/- 1 standard deviation) RP level of 32.9 +/- 10.2%; patients with ALL, 6.6 +/- 3.1%; patients with aplasia, 3.4 +/- 2.0%; and normal patients, 7.9 +/- 2.9%. The difference in RPs between the ITP group and the ALL, aplasia, and normal groups was highly significant (p < 0.0001 each), with no significant difference between the non-ITP groups (p = 0.12). CONCLUSIONS: Measuring RPs by this simple whole-blood cytometric technique discriminated very well between the acute ITP and non-ITP groups. This test has a strong positive predictive value and may prove very useful in the assessment of childhood acute ITP and the screening of candidates for bone marrow aspiration.

Cellular expression of adhesion factors in childhood rhabdomyosarcoma.

Tumor invasion and metastasis are believed to involve the adhesive interaction of tumor cells with extracellular matrix (ECM). This study reports the expression of laminin, fibronectin, thrombospondin, tenascin, and CD44 in rhabdomyosarcoma cells taken from tumors derived from 12 pediatric patients. Twelve paraffin-embedded rhabdomyosarcomas consisting of five alveolar, six embryonal, and one botryoid subtype were examined. All tumors demonstrated positive staining for tenascin and thrombospondin, 10 were positive for fibronectin, 5 positive for laminin, and 4 positive for CD44. Both specimens without cellular staining for fibronectin were of embryonal subtype and no alveolar rhabdomyosarcomas were positive for CD44. No association of the expression of the studied ECM proteins and receptor with the presence of metastatic disease at clinical presentation or with the level of tumor differentiation was found.

Failure of Micro Media FOX Microdilution System to detect decreased susceptibility of Streptococcus pneumoniae to penicillin.

Twelve isolates of Streptococcus pneumoniae with decreased susceptibility by oxacillin screen were susceptible by the FOX panel (Micro Media Systems, Cleveland, Ohio), a commercial microdilution system designed for fastidious organisms. These organisms were found to be moderately susceptible or resistant by broth macrodilution and agar dilution methods. This discrepancy indicates that the FOX panel is not reliable for susceptibility testing of S. pneumoniae.

Comparative activity of cefepime, alone and in combination, against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients.

The comparative in vitro activity and synergy of cefepime were evaluated with clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients. The activity of cefepime, both alone and in combination, was comparable to those of other antibiotics. The clinical efficacy of cefepime in cystic fibrosis patients merits investigation.

The presence and identification of organisms transmitted to dental laboratories.

The potential for infection of dental personnel in the office and dental laboratory by transmission of microorganisms between dentists' offices and commercial dental laboratories does exist. Sixty-seven percent of all materials sent from dental offices to dental laboratories sampled in four cities were contaminated with bacteria of varying degrees of opportunistic pathogenicity. Dental offices and dental laboratories need to practice adequate infection control procedures to prevent possible cross-contamination.

In vitro activities of combinations of aztreonam, ciprofloxacin, and ceftazidime against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from patients with cystic fibrosis.

The in vitro activities of two-drug combinations of aztreonam, ciprofloxacin, and ceftazidime were studied in 96 clinical isolates of Pseudomonas aeruginosa and in 20 clinical isolates of Pseudomonas cepacia from cystic fibrosis patients. Some synergy was observed with each combination used against P. aeruginosa, but synergy was rare when the combinations were used against P. cepacia.

Evaluation of four newer antimicrobial agents in the Avantage susceptibility test system.

Antimicrobial elution disks containing amoxicillin-clavulanic acid (Augmentin), cefotetan, ciprofloxacin, or norfloxacin were tested in the Avantage automated susceptibility test system. Performance was compared against an agar diffusion procedure in a three-site collaborative study. Results of 1,500 comparison with amoxicillin-clavulanic acid showed a full accord (agreement of both systems) of 93.6% and an essential accord (agreement excluding minor discrepancies) of 97.6%. Results for cefotetan showed a full accord of 95.1% and an essential accord of 98.3% by the two methods. Results for both ciprofloxacin and norfloxacin were in full accord for more than 98% of tests with gram-negative bacilli and staphylococci, but tests with enterococci gave 38 and 26.1% minor discrepancies (the result of one method was resistant or susceptible and the result of the other method was intermediate), respectively. The results indicated that the Avantage test system is accurate and reliable and provides appropriate determination of bacterial susceptibility with the four antibiotics tested.