MRONJ risk reduction pathway - 360 degree survey.

Introduction Bisphosphonates and denosumab reduce the risk of skeletal events in some malignancies (for example, breast, myeloma). These drugs carry a significant risk of a difficult-to-manage side effect of medication related osteonecrosis of the jaw (MRONJ). Preventive dental screening and treatment reduces the incidence of MRONJ. A managed clinical network (MCN) has been used to provide a MRONJ risk reduction pathway. A 360 degree survey was undertaken to assess the effectiveness of the pathway.Aim The aim of the 360 degree survey was to evaluate if this preventive pathway fulfilled its aims based on patient and stakeholder responses.Method A multidisciplinary, cross-service, cross-health board MRONJ preventive pathway has been developed. A 360 degree feedback survey of patients and other stakeholders was undertaken.Results Overall, this survey revealed high levels of satisfaction across patients, oncologists, community dental services, general dental services, and hospital managers.Conclusion Alternative ways of delivering MRONJ preventive pathways can be developed and assessed using iterative stakeholder feedback aided by a robust clinical governance framework.

Robust, routine haematology reference ranges for healthy adults.

Accurate, reliable laboratory reference ranges are essential for effective clinical evaluation and monitoring. We present robust reference ranges established for haematology, coagulation and haematinic parameters using the Sysmex XE 2100, CA 1500 and Beckman-Coulter Access analysers. Blood samples were taken from 250 healthy laboratory personnel and routine haematology, coagulation and haematinic parameter analysis performed. Our data represent findings from an extensive study to establish reference ranges in healthy adults.

Clinical guidelines online: do they improve compliance?

BACKGROUND: The introduction of intranet services in a district general hospital provided an opportunity to put evidence based national guidelines online to facilitate access and promote application of best practice in acute medical care. This study evaluated the effectiveness of this approach. METHOD: Local guidelines were made available online at ward terminals after they had been distributed in paper form. An interrupted time series design was used to evaluate the impact on compliance with three preselected guidelines, which addressed the management of suspected deep vein thrombosis, upper gastrointestinal bleeding, and stroke. This was supplemented by a qualitative assessment of the views of medical staff. RESULTS: There was a significant increase in the adherence to the guidelines for stroke when they were made available online, but this was not demonstrable for deep vein thrombosis or upper gastrointestinal bleeding. Qualitative interviews with junior medical staff and consultants after the study was completed revealed that there was confusion regarding the application of the guidelines for deep vein thrombosis and little active support from the gastroenterologists for the guidelines for upper gastrointestinal bleeding. The stroke guidelines were actively promoted by their author and widely supported. CONCLUSION: Making guidelines available online will not be effective unless they are actively promoted and represent a consensus view.

Determination of red cell volume in infants needing blood transfusion.

The total circulating red cell volume (RCV) is a better guide to the oxygen-carrying capacity of the blood in the whole circulation than is the haemoglobin concentration (Hb) or haematocrit in a blood sample. Pre- and post-transfusion RCV (and blood volume (BV)) may be determined by flow cytometry by exploiting antigen differences between transfused donor red cells and the recipient's red cells. This paper describes the use of red cell antigen differences of Duffy, Kidd, MN and RhD between donor and recipient. In 20 infants, transfused on 21 occasions, pretransfusion RCV ranged from 12 to 39 mL kg(-1) body weight. Only at one transfusion could no usable donor-recipient antigen differences be exploited. Measurement of RCV, used routinely, may determine the transfusion requirements of sick infants more accurately, with the aim of normalizing RCV and BV--securing euvolaemia--at the end of the transfusion. This may allow a complete correction of the RCV deficiency at the first occasion of transfusion. This approach may reduce donor exposures and also optimize oxygen transport and organ perfusion of the infant undergoing intensive management, perhaps leading ultimately to improved survival rates and fewer long-term complications of neonatal intensive care.

Postinfection purpura fulminans in a patient heterozygous for prothrombin G20210A and acquired protein S resistance.

Purpura fulminans usually consists of large, often symmetrical, spreading ecchymosis, which may later develop into extensive areas of skin necrosis and peripheral gangrene. Postinfectious purpura fulminans associated with an autoantibody directed against protein S has been described. The interaction and the contribution of recently described mutations such as factor V Leiden and prothrombin G20210A to the development and progression of postinfectious purpura fulminans and venous thrombosis is not known. The authors describe a patient heterozygous for prothrombin G20210A who developed purpura fulminans and extensive venous thrombosis secondary to acquired protein S deficiency.

Clinical use of FFP: results of a retrospective process and outcome audit.

An audit has been carried out on the usage of 216 units of fresh frozen plasma (FFP) issued to 41 patients. This involved the systems of FFP issue, the appropriateness of prescription as well as the recorded benefits. Sixty-six per cent of the initial requests for FFP appeared to satisfy criteria for appropriate use. Review of the case notes resulted in some changes to earlier decisions and a slight increase to 73% of those accepted as valid. Only 94% of the FFP issued could be proved to have been given to identified patients and only 88% of case notes showed the reason for treatment. Pre- and post-treatment coagulation results were available for all patients. In 15% of cases, pretreatment results were not significantly abnormal, and consequently no post-treatment improvement found. Coagulation improvement was documented in 78% of cases, and clinical statements on patient progress noted in 40%. In 80% of cases, the patient received other blood products carrying a potential virus risk. Six of the remaining eight patients were treated to stabilize oral anticoagulation. For these patients, virus-inactivated prothrombin concentrates could have been used, resulting in almost the same reduction in virus transmission risk for the group of 41 patients as could be obtained by using virus-inactivated FFP.

New glucose-6-phosphate dehydrogenase mutations associated with chronic anemia.

We have identified the glucose-6-phosphate dehydrogenase mutations responsible for enzyme deficiency in nine individuals with chronic nonspherocytic hemolytic anemia. We found the variants Tokyo, Iowa, Shinshu, and Guadalajara in British subjects and Kobe in an Italian. In addition we have determined the variant Corum has the mutation 820 G-->A and have found in British subjects the mis-sense mutations 224 T-->C, 488 G-->A and 833 C-->T which have not been described before. Some, but not all, of the mutations involve amino acids located near putative substrate binding sites.

Two-centre evaluation of the Abbott CD3500 blood counter.

The CD3500 blood counter (Abbott Laboratories) is a 33 parameter fully automated blood counter that produces a five part differential count with flagging of leucocyte abnormalities. In this evaluation excellent correlation between CD3500 and Coulter STKR blood counter was found for all red cell and platelet parameters on the 221 samples tested. Studies of carryover, mixing efficiency and precision also gave excellent results. There was a good correlation with manual 400 cell differential counts for neutrophils, lymphocytes, monocytes and eosinophils for the 468 samples compared. Correlation of CD3500 and manual basophil counts was poor. Normal samples stored at 4 degrees C and analysed while cold showed satisfactory stability for WBC, RBC, Hb, MCV and platelets for 48 h and a stable differential for 24 h. Correlation with the differential count produced by the Coulter STKS showed good correlation for neutrophils, lymphocytes, monocytes and eosinophils; correlation with STKS basophils was poor. False positive flagging rate varied between 8.9% (Band and/or IG) and 0.9% (NRBC) depending on the nature of the flag; 5.8% of samples exhibited two or more false positive flags. No significant breakdowns were encountered during the period of the evaluation. The scatterplot displays of laser light scatter produced by the instrument provide an interesting adjunct to conventional morphology.

Flow cytometric determination of pre-transfusion red cell volume in fetuses and neonates requiring transfusion based on RhD+ dilution by transfused D- red cells.

We report a case of feto-maternal haemorrhage and describe a new flow-cytometric method of determining a fetus's or infant's pre-transfusion red cell volume (RCV). We validate this method against an established technique, employing fetal haemoglobin (HbF) dilution, for determining the RCV in fetuses and neonates requiring intravascular transfusion. We discuss advantages and other potential applications of this new method.

Leukemia-associated changes identified by quantitative flow cytometry. III. B-cell gating in CD37/kappa/lambda clonality test.

Normal and malignant B-lymphoid cells were studied for CD37 antigen expression with three-color immunofluorescence (IF) in combination with kappa/lambda light chain staining, and by quantitative immunofluorescence utilizing the QIFI test. Peripheral B cells brightly expressed CD37 antigen (median 80-114 x 10(3) molecules/cell). Moderate to high levels (> 20 x 10(3)/cell) of CD37 expression were detected in 364 in 366 cases of peripheral B-cell disorders including all cases of B-ALL, B-cell lymphomas and B-CLL as well as eight of ten cases of PLL. By contrast, slg- B-cell precursors and other cell types in normal bone marrow (BM) were CD37-/CD37dull (< 10 x 10(3) molecules/cell). The negativity for CD37 or only CD37dull expression was confirmed in 180 of 182 cases of precursor B-ALL and 196 cases of non-B malignancies. Among the CD37 cluster, the RFB7 antibody of IgM class showed the weakest binding to non-B cells. In 64 normal samples of blood and BM the CD37+ gated cells showed normal kappa/lambda ratios as expected, while in 100 cases of B malignancy striking changes such as kappa/lambda monoclonality (79%) and aberrant slg- or sigdull expression (21%) were seen among the gated CD37+ B cells. The CD37/kappa/lambda test identified as few as 0.5% kappa+ or lambda- monoclonal B cells admixed to normal BM: circulating B-lymphoma cells were seen in nine patients with morphologically normal blood count. The discrimination of the Kolmogorov-Smirnov (KS) test for kappa/lambda excess was also improved by CD37+ B gating. Thus CD37+ B-cell gating and kappa/lambda analysis is a simple and sensitive routine test, e.g. when combined with autogating on a Cytoron-Absolute cytometer, for identifying malignant B cells in minimally involved BM and blood.

Immunophenotyping of normal lymphocytes.

We report the data of direct and indirect immunofluorescence labelling of peripheral blood mononuclear cells obtained from 40 normal controls and nine patients having blood tests for non-haematological disorders (PNHD controls) using flow cytometric analysis. Polyclonal and monoclonal antibodies were used to define the expression of cell surface antigen of T cells, their subsets, B cells, natural killer cells (NK) and myeloid cells. Normal values of absolute number and percentages of each of the populations of mononuclear cells were established and were sufficiently reproducible to be of clinical use. The percentages of positive values of T cells, T-cell subsets, and B cells in ten normal controls when mononuclear cells were used, were comparable to those using whole blood lysis, APAAP immuno-alkaline phosphatase, and E and M rosettes. The results obtained were similar in both the normal and PNHD controls. In most instances the percentage recovery of identified T, B and NK cells was complete. Currently we are using the results as reference values for lymphoid sub-populations in normal controls.

Combination chemotherapy including epirubicin for the management of non-Hodgkin's lymphoma.

One hundred patients with untreated non-Hodgkin's lymphoma were entered in a prospective randomized study in South and West Wales designed to assess the value of the anthracycline antibiotic, epirubicin (4'-epidoxorubicin), in their management. Patients with low grade histology and progressive disease were randomized to receive either epirubicin, vincristine and prednisolone (EVP) or cyclophosphamide, vincristine and prednisolone (CVP). The response rate of 81% in patients receiving EVP with complete remission rate of 52% were similar to a response rate of 88% and complete remission rate of 58% for patients receiving CVP. No difference was observed in survival between the two groups. Patients with high grade lymphoma were randomized to receive either cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or cyclophosphamide, epirubicin, vincristine and prednisolone (CEOP). The response rate was 71% for CHOP and 84% for CEOP. The complete remission rates were 46% for CHOP and 61% for CEOP. The cardiotoxicity of the two anthracyclines were monitored closely in 45 patients using measurements of systolic time intervals. Patients receiving epirubicin tolerated higher dose per course and higher total cumulative dose with less evidence of compromised left ventricular function than patients receiving doxorubicin. Epirubicin is an effective agent when used in combination chemotherapy in both low grade and high grade lymphoma with less toxicity than doxorubicin.

Erythropoiesis and iron metabolism in Hodgkin's disease.

Recently developed techniques for the investigation of iron kinetics were used to study the disturbance of iron metabolism in 19 untreated patients with Hodgkin's diseases (HD). The erythroid abnormality in newly diagnosed HD appears to be confined to those patients with systemic symptoms of weight loss, night sweats and fever, and consists of depression of marrow erythroid activity. These patients had a significnatly lower haemoglobin and serum iron concentration and a higher serum ferritin concentration, both when compared to normal subjects and to those patients with HD who lacked systemic symptoms. Ineffective erythropoiesis and red-cell destruction were not significantly increased. The present findings, confirm that HD patients with systemic symptoms have a depression of erythropoiesis, and that in these patients the marrow fails to respond to the stimulus of mild anaemia.

Systolic time interval as index of schedule--dependent doxorubicin cardiotoxicity in patients with acute myelogenous leukaemia.

The ratio of the pre-ejection period to the left ventricular ejection time (PEP:LVET) was measured in two groups of patients with acute myeloblastic leukaemia (AML) receiving the anthracycline antibiotic doxorubicin (DXR). Patients receiving high doses of DXR per course (about 90 mg/m2) showed a significant increase in the PEP:LVET ratio irrespective of the total cumulative dose. At a lower dose per course (less than 50mg/m2) only patients who had a total cumulative dose of over 450 mg/m2 showed significant increases in ratio. ECG changes were seen in both groups of patients but did not correlate significantly with the dosage. These findings, which suggest that DXR cardiotoxicity is schedule dependent, are important in the design of schedules of DXR for treating cancer and in interpreting the changes in systolic time intervals (STIs) observed with different schedules. Measurement of the STI is a simple and convenient method of assessing DXR cardiotoxicity. While a total DXR dose of 550 mg/m2 should not normally be exceeded, by carefully monitoring the STI the recommended total dose may be exceeded safely in selected patients.

Factor VIII inhibitor and bronchogenic carcinoma.

An inhibitor to procoagulant factor VIII (FVIIIC) developed in a patient three years after palliative resection of a bronchogenic carcinoma. The inhibitor was not active against ristocetin cofactor but possibly had some activity against factor XI. It responded to immunosuppressive therapy. This is apparently the first reported association of carcinoma and factor VIII inhibitor.

An assessment of laparotomy in the management of patients with Hodgkin's disease.

Planned laparotomy and splenectomy has been a safe investigation for sixty patients with clinical Stage I, II or III Hodgkin's disease. Twenty-four of the 60 patients (40%) changed stage and 18 patients had their treatment altered as a consequence of the procedure. Forty-three per cent of patients without a palpably enlarged spleen had unsuspected disease when the organ was examined pathologically, although a false positive spleen was uncommon. Eight of 55 patients (14.5%) had intra-abdominal disease which was not detected by lymphangiography. Intra-abdominal disease occurred with all histological sub-types and was found in two patients who had clinical Stage I disease and lymphocyte predominance in their node histology. Sarcoid-like granulomata were found in ten patients, seven in the spleen, one in the liver and spleen, one in the skin and one in the original node biopsy. In the majority of patients, granulomata were associated with nodular sclerosing or mixed cellular histology. In all ten patients the Hodgkin's disease was suppressed by appropriate chemotherapy and disease has not recurred. No patient has shown any clinical evidence of sarcoidosis and the Kveim test done in three patients was negative. Our experience encourages us to recommend staging laparotomy for all adult patients with Hodgkin's disease which does not show obvious generalized spread beyond lymph nodes.