CyBorD-DARA in Newly Diagnosed Transplant-Eligible Multiple Myeloma: Results from the 16-BCNI-001/CTRIAL-IE 16-02 Study Show High Rates of MRD Negativity at End of Treatment.

The phase 1b 16-BCNI-001/CTRIAL-IE 16-02 CyBorD-DARA trial investigated the combination of Daratumumab with cyclophosphamide, bortezomib and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM), followed by autologous stem cell transplantation and Daratumumab maintenance. CR/sCR rates were 50% after transplant and 62.5% at end of treatment. The overall percentage of patients achieving complete response or better was 77.8%. Progression-free survival rate at end of maintenance was 81.3% and estimated 2-year overall survival was 88.9%. 37.5% of patients demonstrated sustained MRD negativity to a level of 10-5 from transplant to analysis at EOT. In this phase 1b study, we have shown CyBorD-DARA to be an effective and well-tolerated immunomodulatory agent-free regiment in transplant-eligible NDMM.

The Rap1 small GTPase is a critical mediator of the effects of stress on prefrontal cortical dysfunction.

The neural molecular and biochemical response to stress is a distinct physiological process, and multiple lines of evidence indicate that the prefrontal cortex (PFC) is particularly sensitive to, and afflicted by, exposure to stress. Largely through this PFC dysfunction, stress has a characterized role in facilitating cognitive impairment, which is often dissociable from its effects on non-cognitive behaviors. The Rap1 small GTPase pathway has emerged as a commonly disrupted intracellular target in neuropsychiatric conditions, whether it be via alterations in Rap1 expression or through alterations in the expression of direct and specific upstream Rap1 activators and inhibitors. Here we demonstrate that escalating, intermittent stress increases Rap1 in mouse PFC synapses, results in cognitive impairments, and reduces the preponderance of mature dendritic spines in PFC neurons. Using viral-mediated gene transfer, we reveal that the hyper-induction of Rap1 in the PFC is sufficient to drive stress-relevant cognitive and synaptic phenotypes. These findings point to Rap1 as a critical mediator of stress-driven neuronal and behavioral pathology and highlight a previously unrecognized involvement for Rap1 in novelty-driven PFC engagement.

CyBorD-DARA is potent initial induction for MM and enhances ADCP: initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study.

Daratumumab (DARA) has shown impressive activity in combination with other agents for the treatment of multiple myeloma (MM). We conducted a phase 1b study to assess the safety and preliminary efficacy, as well as potential mechanisms of action, of DARA (16 mg/kg) in combination with a weekly schedule of subcutaneous bortezomib (1.3-1.5 mg/m2), cyclophosphamide (150-300 mg/m2), and dexamethasone (40 mg) (CyBorD DARA) as initial induction before autologous stem cell transplantation (ASCT). Eligible patients were ≤70 years of age with untreated MM requiring treatment and who lacked significant comorbidities. A total of 18 patients were enrolled. Their median age was 56 years (range, 32-66 years), and all patients had Eastern Cooperative Oncology Group performance status ≤1. The International Staging System stages were I, II, and III in 78%, 17%, and 6% of patients, respectively; 28% of patients had high-risk genetic features. There was no dose-limiting toxicity, and the incidence of grade 3 or 4 infection or neutropenia was <10%. On an intention-to-treat basis, 94% achieved ≥very good partial response with ≥complete response in 44% of patients. Among 14 of 15 patients who underwent ASCT and were evaluable for response, all 14 achieved at least very good partial response, with 8 (57%) of 14 achieving complete response. After ASCT, 10 (83%) of 12 patients in whom minimal residual disease analysis was possible were negative at a sensitivity of 10-5 (56% on intention-to-treat/whole study population) according to next-generation sequencing. Flow cytometry analysis of patient samples indicated CyBorD DARA induced activation of macrophage-mediated antibody-dependent cellular phagocytosis. This trial was registered at www.clinicaltrials.gov as #NCT02955810.

The dendritic spine morphogenic effects of repeated cocaine use occur through the regulation of serum response factor signaling.

The nucleus accumbens (NAc) is a primary brain reward region composed predominantly of medium spiny neurons (MSNs). In response to early withdrawal from repeated cocaine administration, de novo dendritic spine formation occurs in NAc MSNs. Much evidence indicates that this new spine formation facilitates the rewarding properties of cocaine. Early withdrawal from repeated cocaine also produces dramatic alterations in the transcriptome of NAc MSNs, but how such alterations influence cocaine's effects on dendritic spine formation remain unclear. Studies in non-neuronal cells indicate that actin cytoskeletal regulatory pathways in nuclei have a direct role in the regulation of gene transcription in part by controlling the access of co-activators to their transcription factor partners. In particular, actin state dictates the interaction between the serum response factor (SRF) transcription factor and one of its principal co-activators, MAL. Here we show that cocaine induces alterations in nuclear F-actin signaling pathways in the NAc with associated changes in the nuclear subcellular localization of SRF and MAL. Using in vivo optogenetics, the brain region-specific inputs to the NAc that mediate these nuclear changes are investigated. Finally, we demonstrate that regulated SRF expression, in turn, is critical for the effects of cocaine on dendritic spine formation and for cocaine-mediated behavioral sensitization. Collectively, these findings reveal a mechanism by which nuclear-based changes influence the structure of NAc MSNs in response to cocaine.

General practitioner views on the determinants of test ordering: a theory-based qualitative approach to the development of an intervention to improve immunoglobulin requests in primary care.

BACKGROUND: Research suggests that variation in laboratory requesting patterns may indicate unnecessary test use. Requesting patterns for serum immunoglobulins vary significantly between general practitioners (GPs). This study aims to explore GP's views on testing to identify the determinants of behaviour and recommend feasible intervention strategies for improving immunoglobulin test use in primary care. METHODS: Qualitative semi-structured interviews were conducted with GPs requesting laboratory tests at Cork University Hospital or University Hospital Kerry in the South of Ireland. GPs were identified using a Health Service Executive laboratory list of GPs in the Cork-Kerry region. A random sample of GPs (stratified by GP requesting patterns) was generated from this list. GPs were purposively sampled based on the criteria of location (urban/rural); length of time qualified; and practice size (single-handed/group). Interviews were carried out between December 2014 and February 2015. Interviews were transcribed verbatim using NVivo 10 software and analysed using the framework analysis method. Emerging themes were mapped to the theoretical domains framework (TDF), which outlines 12 domains that can enable or inhibit behaviour change. The behaviour change wheel and behaviour change technique (BCT) taxonomy were then used to identify potential intervention strategies. RESULTS: Sixteen GPs were interviewed (ten males and six females). Findings suggest that intervention strategies should specifically target the key barriers to effective test ordering, while considering the context of primary care practice. Seven domains from the TDF were perceived to influence immunoglobulin test ordering behaviours and were identified as 'mechanisms for change' (knowledge, environmental context and resources, social/professional role and identity, beliefs about capabilities, beliefs about consequences, memory, attention and decision-making processes and behavioural regulation). Using these TDF domains, seven BCTs emerged as feasible 'intervention content' for targeting GPs' ordering behaviour. These included instructions on how to effectively request the test (how to perform behaviour), information on GPs' use of the test (feedback on behaviour), information about patient consequences resulting from not doing the test (information about health consequences), laboratory/consultant-based advice/education (credible source), altering the test ordering form (restructuring the physical environment), providing guidelines (prompts/cues) and adding interpretive comments to the results (adding objects to the environment). These BCTs aligned to four intervention functions: education, persuasion, environmental restructuring and enablement. CONCLUSIONS: This study has effectively applied behaviour change theory to identify feasible strategies for improving immunoglobulin test use in primary care using the TDF, 'behaviour change wheel' and BCT taxonomy. The identified BCTs will form the basis of a theory-based intervention to improve the use of immunoglobulin tests among GPs. Future research will involve the development and evaluation of this intervention.

The presence of C/EBPα and its degradation are both required for TRIB2-mediated leukaemia.

C/EBPα (p42 and p30 isoforms) is commonly dysregulated in cancer via the action of oncogenes, and specifically in acute myeloid leukaemia (AML) by mutation. Elevated TRIB2 leads to the degradation of C/EBPα p42, leaving p30 intact in AML. Whether this relationship is a cooperative event in AML transformation is not known and the molecular mechanism involved remains elusive. Using mouse genetics, our data reveal that in the complete absence of C/EBPα, TRIB2 was unable to induce AML. Only in the presence of C/EBPα p42 and p30, were TRIB2 and p30 able to cooperate to decrease the latency of disease. We demonstrate that the molecular mechanism involved in the degradation of C/EBPα p42 requires site-specific direct interaction between TRIB2 and C/EBPα p42 for the K48-specific ubiquitin-dependent proteasomal degradation of C/EBPα p42. This interaction and ubiquitination is dependent on a critical C terminal lysine residue on C/EBPα. We show effective targeting of this pathway pharmacologically using proteasome inhibitors in TRIB2-positive AML cells. Together, our data show that excess p30 cooperated with TRIB2 only in the presence of p42 to accelerate AML, and the direct interaction and degradation of C/EBPα p42 is required for TRIB2-mediated AML.

Ionizing radiation exposure as a result of diagnostic imaging in patients with lymphoma.

PURPOSE: Survival rates among patients with lymphoma continue to improve. Strategies aimed at reducing potential treatment-related toxicity are increasingly prioritized. While radiological procedures play an important role, ionizing radiation exposure has been linked to an increased risk of malignancy, particularly among individuals whose cumulative radiation exposure exceeds a specific threshold (75 millisieverts). METHODS: Within this retrospective study, the cumulative radiation exposure dose was quantified for 486 consecutive patients with lymphoma. RESULTS: The median estimated total cumulative effective dose (CED) of ionizing radiation per subject was 69 mSv (42-118). However, younger patients (under 40 years) had a median CED of 89 mSv (55-124). CONCLUSION: This study highlights the considerable radiation exposure occurring among patients with lymphoma as a result of diagnostic imaging. To limit the risk of secondary carcinogenesis, consideration should be given to monitoring cumulative radiation exposure in individual patients as well as considering imaging modalities, which do not impart an ionizing radiation dose.

Progestogens and membrane-initiated effects on the proliferation of human breast cancer cells.

OBJECTIVES: Evidence is accumulating that progestogens may play a crucial role in the development of breast cancer under contraception and hormone therapy in reproductive and menopausal women. Progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer may be important in tumorigenesis and thus may increase breast cancer risk. The aim of this project was to investigate the influence of progesterone and nine synthetic progestins on MCF-7 breast cancer cells overexpressing PGRMC1. METHODS: MCF-7 cells were stably transfected with PGRMC1 expression plasmid (WT-12). To test the effects of progestogerone (P) and the synthetic progestins chlormadinone acetate (CMA), desogestrel (DSG), drospirenone (DRSP), dydrogesterone (DYD), levonorgestrel (LNG), medroxyprogesterone acetate (MPA), nomegestrol (NOM) and norethisterone (NET) on cell proliferation, MCF-7 and WT-12 cells were stimulated with different concentrations (0.01-1 µmol/l). RESULTS: In MCF-7 cells, DRSP, DSG, DYD, LNG and NET increased the proliferation at 1 µmol/l, the effect being highest for NET with about 20%. In WT-12 cells, the same progestins, but additionally MPA, showed a significant increase, which was much higher (30-245%) than in MCF-7 cells. Here again, NET showed the highest proliferative effect. No effect was found for CMA, NOM and P. CONCLUSION: Some synthetic progestins trigger a proliferative response of PGRMC1-overexpressed MCF-7 cancer cells. The effect of progestogens on breast cancer tumorigenesis may clearly depend on the specific pharmacology of the various synthetic progestins.

Control of interneuron dendritic growth through NRG1/erbB4-mediated kalirin-7 disinhibition.

Neuregulin 1 (NRG1) is a secreted trophic factor that activates the postsynaptic erbB4 receptor tyrosine kinase. Both NRG1 and erbB4 have been repeatedly associated with schizophrenia, but their downstream targets are not well characterized. ErbB4 is highly abundant in interneurons, and NRG1-mediated erbB4 activation has been shown to modulate interneuron function, but the role for NRG1-erbB4 signaling in regulating interneuron dendritic growth is not well understood. Here we show that NRG1/erbB4 promote the growth of dendrites in mature interneurons through kalirin, a major dendritic Rac1-GEF. Recent studies have shown associations of the KALRN gene with schizophrenia. Our data point to an essential role of phosphorylation in kalirin-7's C terminus as the critical site for these effects. As reduced interneuron dendrite length occurs in schizophrenia, understanding how NRG1-erbB4 signaling modulates interneuron dendritic morphogenesis might shed light on disease-related alterations in cortical circuits.

Self-reported knowledge, attitudes and behaviour towards evidence-based practice of occupational therapy students in Ireland.

It is widely accepted that the occupational therapy profession needs to incorporate research findings into clinical practice so as to improve client outcomes. The purpose of this study was to investigate the knowledge and attitudes toward evidence-based practice (EBP) of occupational therapy students in the Republic of Ireland. A validated questionnaire was used to survey the population of final-year students from the four universities in Ireland in 2008. There was a response rate of 77% (n = 86) to the Knowledge, Attitude and Behaviour Questionnaire. All students reported that they had a clear understanding of EBP and were willing to practice EBP in the future. The majority (85%, n = 73) reported accessing evidence weekly or more often. Lack of time and fieldwork educators not practising EBP were important barriers for 31% (n = 27) and 27% (n = 23), respectively. Over half (55%, n = 47) reported difficulty in finding evidence. The internet (28%, n = 24) and textbooks (27%, n = 23) were the most popular sources of evidence. Limitations include the self-report, cross-sectional design. Future research could include longitudinal studies to understand the transfer of learning into clinical practice.

Nd:YAG laser hyaloidotomy for valsalva pre-macular haemorrhage.

AIM: To report a case of successful drainage of a large pre-macular haemorrhage using laser photo-disruption of the posterior hyaloid membrane. MATERIALS AND METHODS: A case report. RESULTS: A 47-year-old man presented acutely to our emergency department complaining of a 24-h history of sudden onset, painless and persistent loss of vision in his left eye. Immediately before noticing this loss of vision, he had been vomiting violently from excessive alcohol intake. The left visual acuity was counting fingers. Dilated fundoscopy of the left eye revealed a large pre-macular haemorrhage which was 14 disc diametres in size. Clotting investigations were normal. A diagnosis of valsalva retinopathy was made and the patient elected to receive a prompt neodymium-doped yttrium aluminium garnet (Nd:YAG) laser posterior hyaloidotomy as an outpatient. At 1 week follow-up, the haemorrhage had drained completely into the vitreous space revealing a healthy macula and the visual acuity had improved to 6/12 unaided. At 6-month follow-up the left visual acuity stabilised at 6/9 unaided. CONCLUSION: Nd:YAG laser posterior hyaloidotomy is a useful outpatient procedure for successful clearance of large pre-macular haemorrhages that offers patients rapid recovery of visual acuity and the avoidance of more invasive intraocular surgery.

The pathophysiology of cigarette smoking and age-related macular degeneration.

Age-related macular degeneration (AMD) is the most common form of visual impairment, in people over 65, in the Western world. AMD is a multifactorial disease with genetic and environmental factors influencing disease progression. Cigarette smoking is the most significant environmental influence with an estimated increase in risk of 2- to 4-fold. Smoke-induced damage in AMD is mediated through direct oxidation, depletion of antioxidant protection, immune system activation and atherosclerotic vascular changes. Moreover, cigarette smoke induces angiogenesis promoting choroidal neovascularisation and progression to neovascular AMD. Further investigation into the effects of cigarette smoke through in vitro and in vivo experimentation will provide a greater insight into the pathogenesis of age-related macular degeneration.

Phase I/II safety study of transfusion of prion-filtered red cell concentrates in transfusion-dependent patients.

BACKGROUND AND OBJECTIVES: Variant Creutzfeldt-Jakob (vCJD) is a fatal transfusion transmissible prion infection. No test for vCJD in the donor population is currently available. Therefore, prion removal by filtration of red cell concentrate (RCC) is an attractive option for prevention. MATERIALS AND METHODS: Twenty patients were recruited with ethical permission, to receive clinically necessary transfusion containing one unit of pfRCC. Follow-up at 24 hours, 6 weeks and 6 months was undertaken. A second pfRCC was administered to 6 patients with similar follow up. pfRCC were prepared using the CE marked P-Capt device by the IBTS. RESULTS: In 20 transfused patients undergoing one exposure to a prion filtered unit, no attributable adverse events were noted. A subset of these (n = 6) underwent re-exposure to a further filtered unit without incident. CONCLUSIONS: This phase 1/11 clinical study provides encouraging data on safety of prion filtration which can be used to plan more extensive studies on the use of filtered blood in adults and children.

Membrane-initiated effects of progesterone on proliferation and activation of VEGF in breast cancer cells.

OBJECTIVE: Progesterone influences mammary gland development and probably breast cancer tumorigenesis and functions by regulating a broad spectrum of physiological processes. We investigated receptor membrane-initiated actions of progesterone in MCF-7 breast cancer cells via progesterone receptor membrane component 1 (PGRMC1). DESIGN AND METHOD: The expression of PGRMC1 in breast cancer was verified by immune fluorescent analysis of paraffin sections. MCF-7 cells were transfected with PGRMC1 (wild type) or PGRMC1 variants. These cells were stimulated with a membrane-impermeable progesterone (P4) conjugate (P4-BSA-fluorescein isothiocyanate, P4-BSA-FITC, 10(-6) mol/l) or unconjugated progesterone (P4, 10(-6) mol/l) in the presence or absence of the progesterone receptor blocker RU-486 (10(-6) mol/l). Additionally, the effects on the expression of vascular endothelial growth factor A (VEGF-A) were determined using quantitative real-time polymerase chain reaction. RESULTS: PGRMC1 is perinuclearly localized in breast cancer cells. Western Blot analysis suggests that PGRMC1 is phosphorylated at serine 180. MCF-7-PGRMC1 (S180A) cells show an approximately 35% increase in proliferation after incubation with P4-BSA-FITC compared to MCF-7 control and MCF-7-PGRMC1 (wild type) cells. This effect cannot be blocked by RU-486. P4 reduced proliferation of MCF-7-PGRMC1 cells by approximately 10% compared to untreated controls. P4-BSA-FITC treatment led to a roughly three-fold activation of VEGF-A gene expression compared to MCF-7 cells. CONCLUSION: PGRMC1 is expressed in breast cancer tissue and mediates an RU-486-independent proliferative signal. It might also contribute to VEGF-induced neovascularization in tumor tissue. Thus, screening for PGRMC1 expression might be of interest to identify women with a higher expression of PGRMC1 and who might thus be susceptible for breast cancer development under hormone replacement therapy.

Warfarin prevalence, indications for use and haemorrhagic events.

Warfarin, the standard oral anticoagulant drug used in Ireland, is a widely prescribed medication, particularly in the elderly. A HSE Mid-Western Area wide audit was undertaken over a 12-month period to examine the prevalence and indications for warfarin use and haemorrhagic complications associated with the drug. Every patient receiving warfarin therapy over a 13-week period was included (2564). The age standardised rate varied from 0.09% of 35-39 year olds to 6.1% of 80-84 year olds. Atrial fibrillation was the most common indication (54%) in patients attending the Mid-Western Regional Hospital anticoagulation clinic. The annual cumulative incidence of adverse haemorrhagic events in patients with a recorded INR > or = 5.0 episode was 16.6%. The incidence of major and minor haemorrhagic events per INR > or = 5.0 episode was 1.3% and 15.3% respectively. The most common sites of haemorrhage were genitourinary (39%) and gastrointestinal (27%). No fatal or intracranial haemorrhage relating to episodes of over-anticoagulation were reported during the audit period. The most frequent reason for over-anticoagulation was drug interaction (43%). In 74% of patients, the elevated INR was reversed by omitting or reducing warfarin dose. In 17% of cases, vitamin K was administered. Only 3% of incidents were treated with fresh frozen plasma or prothrombin complex concentrates.

Long-term outcomes of laparoscopic antireflux surgery for gastroesophageal reflux disease (GERD)-related airway disorder.

UNLABELLED: A strong link exists between gastroesophageal reflux disease (GERD) and airway diseases. Surgical therapy has been recommended as it is more effective than medical therapy in the short-term, but there is little data on the effectiveness of surgery long-term. We analyzed the long-term response of GERD-related airway disease after laparoscopic anti-reflux surgery (LARS). METHODS: In 2004, we contacted 128 patients with airway symptoms and GERD who underwent laparoscopic antireflux surgery (LARS) between 12/1993 and 12/ 2002. At median follow-up of 53 months (19-110 mo) we studied the effects on symptoms, esophageal acid exposure, and medication use and we analyzed the data to determine predictors of successful resolution of airway symptoms. RESULTS: Cough, hoarseness, wheezing, sore throat, and dyspnea improved in 65-75% of patients. Heartburn improved in 91% (105/116) of patients and regurgitation in 92% (90/98). The response rate for airway symptoms was the same in patients with and without heartburn. Almost every patient took proton pump inhibitors (PPIs) preoperatively (99%, 127/128) and 61% (n = 78) were taking double or triple dose. Postoperatively, 33% (n = 45) of patients were using daily antiacid therapy but no one was on double dose. The only factor that predicted a successful surgical outcome was the presence of abnormal reflux in the pharynx as determined by 24-hour pharyngeal pH monitoring. One hundred eleven (87%) patients rated their results as excellent (n = 78, 57%) or good (n = 33, 24%). CONCLUSION: LARS provides an effective and durable barrier to reflux, and in so doing improves GERD-related airway symptoms in approximately 70% of patients and improves typical GERD symptoms in approximately 90% of patients. Pharyngeal pH monitoring identifies those patients more likely to benefit from LARS, but better diagnostic tools are needed to improve the response of airway symptoms to that of typical esophageal symptoms.

Medium- and long-term outcome of laparoscopic redo fundoplication.

BACKGROUND: For a small subset of patients, laparoscopic fundoplication fails, typically resulting in recurrent reflux or severe dysphagia. Although redo fundoplications can be performed laparoscopically, few studies have examined their long-term efficacy. METHODS: Using a prospectively maintained database, the authors identified and contacted 41 patients who had undergone redo laparoscopic fundoplications at the University of Washington between 1996 and 2001. The median follow-up period was 50 months (range, 20-95 months). Current symptoms were compared with those acquired and entered into the authors' database preoperatively. Patients also were asked to return for esophageal manometry and pH testing. RESULTS: All redo fundoplications were performed laparoscopically. There were no conversions. The most common indication for redo fundoplication was recurrent reflux. The most common anatomic abnormality was a herniated wrap. Heartburn improved in 61%, regurgitation in 69%, and dysphagia in 74% of the patients. Complete resolution of these symptoms was achieved, respectively, in 45%, 41% and 38% of these same patients. Overall, 68% of the patients rated the success of the procedure as either "excellent" or "good," and 78% said they were happy they chose to have it. For those who underwent reoperation for gastroesophageal reflux disease, distal esophageal acid exposure according to 24-h pH monitoring decreased after redo fundoplication from 15.7% +/- 18.1% to 3.4% +/- 3.6% (p = 0.041). CONCLUSION: Although not as successful as primary fundoplication, a majority of patients can expect durable improvement in their symptoms with a laparoscopic redo fundoplication.

The issue of anti-D: an integrated seamless approach from recognition of need to bedside administration.

BACKGROUND: The appropriate and timely administration of Anti-D immunoglobulin to Rhesus (D) negative women who have delivered Rhesus (D) positive babies is a vital part of obstetric care. Anti-D has an especially high profile in Ireland because of the tragic inadvertent transmission of Hepatitis C to Irish women in past decades. AUDIT: We have reviewed our policy and procedures pertaining to the administration of Anti-D for sensitising events during pregnancy and postnatally, in the Mid-Western Health Board in 1999/2000. As a result, major changes were made in the storage, issue, recording and administration of Anti-D. New procedures in the transfusion laboratory and in the maternity hospital have been accepted by scientists and midwives and supported by haematology and obstetric medical staff. The pharmacy and haematology laboratory no longer have a role in this programme. IMPLEMENTATION OF MULTI-DISCIPLINARY CHANGE MANAGEMENT: As a result of these changes, the storage, issuing and tracking of Anti-D has become the responsibility of the hospital blood bank. Measurement offoeto-maternal haemorrhage (FMH) is now the responsibility of bio medical scientists in blood bank, utilising both flow cytometry (increasingly recognised as the gold standard method) and the Kleihauer method (Kleihauer-Betke). The programme has moved from a doctor-administered IV Anti-D Ig, to a midwife-administered IM preparation. Prescription remains the responsibility of the doctor. These changes are facilitated by the protocol guided issue of the appropriate dose of Anti-D Ig by bio medical scientists to midwives. The issue of the Anti-D Ig occurs simultaneously with issue of results of mother and baby's serology testing and estimation of volume of FMH. These major changes have been guided by audit and needs assessment and require close liaison between medical, nursing and laboratory scientific staff in haematology, transfusion and obstetrics. CRITICAL INCIDENT AUDIT-CASE REPORT: Before new procedures became official policy, a critical incident audit allowed us to pilot our protocol and to revise it using draft new procedures. In this critical incident we describe successful management of a patient with a large foeto-maternal haemorrhage. This incident supported the need for the procedural enhancements already underway. This critical incident re-emphasised the need for the planned systems improvements to be introduced quickly.

Autologous stem cell transplantation in myeloma: the St James's Hospital experience, 1997-2003.

BACKGROUND: High-dose treatment with autologous stem cell transplantation (ASCT) has become the standard of care for patients with myeloma below the age of 65 years. AIMS: We report an audit of 60 patients (median age: 52.5 years) who underwent ASCT in the National Bone Marrow Transplant centre in St James's Hospital in Dublin between 1997 and 2003 inclusive. METHODS: Clinical and laboratory data were retrieved from patient medical records and hospital information management systems. RESULTS: Thirty-six patients had IgG, 11 IgA, 1 IgD, 9 light chain and 3 non-secretory MM. Fifty-seven (95%) patients received anthracycline-corticosteroid combination chemotherapy prior to autografting. There was no transplant-related mortality (TRM). Complete (CR) and Partial Responses (PR) were seen in 16 (29.6%) and 29 (53.7%) of those evaluable (n = 54 (90%)). The actuarial Progression-Free (PFS) and Overall Survival (OS) rates at five years are 13% and 55% respectively. CONCLUSION: Centre outcome is comparable to published international series and supports the use of ASCT in the treatment of this malignancy.