A data-driven approach to improving clinical outcomes in cardiac care.

The performance improvement department at The Queen's Medical Center (QMC) in Honolulu, has been monitoring the outcomes of cardiovascular interventional procedures and cardiothoracic surgical procedures. By using an institution-wide database as well as participating in national cardiac databases, a set of clinical indicators is tracked, and quarterly reports are provided to the cardiovascular medicine (CV) and thoracic and cardiovascular surgery (TCV) services. After reviewing the data, a combined CV/TCV/anesthesia morbidity and mortality committee meets monthly to further evaluate the data, review cases, and formulate action plans based upon the findings. Using these tools and methods, we have seen a marked improvement in clinical outcomes among cardiac patients.

Home treatment of mild to moderate bleeding episodes using recombinant factor VIIa (Novoseven) in haemophiliacs with inhibitors.

OBJECTIVE: To assess the safety and efficacy of a fixed dose of recombinant activated factor VII (rFVIIa; NovoSeven) in the home setting for mild to moderately severe joint, muscle; and mucocutaneous bleeding episodes in patients with haemophilia A or B with inhibitors. DESIGN: Multicentre, open-label, single arm, phase III study of one year duration. METHODS; Patients or their caregivers administered up to three doses of rFVIIa (90 microg/kg i.v.) at 3 h intervals within 8 h of the onset of a mild to moderate bleeding episode. Once the subject considered that rFVIIa had been "effective" with regard to haemostasis (after 1-3 injections), one further (maintenance) dose of rFVIIa was administered. RESULTS: Of 60 patients enrolled, 56 experienced at least one bleed, and 46 completed the one year study. 614 of 877 bleeds (70%) were evaluable according to protocol definitions. Haemostasis was rated as "effective" in 92% (566/614) of evaluable bleeds after a mean of 2.2 injections. For successfully treated episodes, the time from onset of bleeding until administration of the first injection was 1.1+/-2.0 h (mean+/-SD). Twenty-four hours after initial successful response, haemostasis was reported as having been maintained in 95% of cases. Efficacy was comparable for muscle, joint and target joint, and mucocutaneous bleeding episodes. In an intent-to-treat analysis of all 877 bleeding events, efficacy outcomes were equivalent to the evaluable bleeds, with an effective response in 88% of treated episodes. Treatment-related adverse events occurred in 32 (3% of all) bleeding episodes and consisted of re-bleeds/new bleeds in more than 50% (18/32) of these events. A single episode of superficial thrombophlebitis was the only thrombotic complication encountered, and there were no patient withdrawals due to adverse events. Development of FVII(a) antibodies could not be detected, and hypersensitivity reactions to rFVIIa were not reported. CONCLUSION: rFVIIa is effective and well tolerated when used in the home setting to treat mild to moderate bleeding episodes in patients with haemophilia A or B with inhibitors.

Subacute (acute, persistent) thrombotic microangiopathy.

Six patients with prolonged acute courses of thrombotic microangiopathy are reviewed. These patients had in common courses of acute disease requiring plasma support for more than 3 months, with subsequent complete remission. Plasma support requirements may be prodigious, and the acute course may require more than 100 plasma exchanges before a stable remission is achieved. These patients appear to represent a subset of thrombotic microangiopathy distinct from the more common acute T.T.P. course, which resolves in 3-6 weeks, and the chronic relapsing pattern, which may have a short or prolonged acute course.

An ultrastructural study of the renal juxtaglomerular apparatus and extraglomerular mesangium in patients with systemic lupus erythematosus.

Experimental studies have indicated that the glomerular mesangium may function by phagocytosis of various circulating substances which are then processed and flow to the juxtaglomerular apparatus (JGA) region and into the intercellular spaces of the macula densa. An electron-micrographic study of the juxtaglomerular apparatus and extramesangial region in systemic lupus erythematosus (SLE) was undertaken. In only five of 39 cases (13%) of SLE were discrete electron-dense "immune-type" deposits noted in the JGA region. In four of those patients, there were also a large number of variously-sized electron-dense deposits in the glomerular mesangial and capillary wall regions, Bowman's capsule, tubular basement membranes, renal interstitium, or in the nearby periglomerular arterioles. The paucity of demonstrable discrete electron-dense deposits in the JGA regions in this study suggests that the deposits noted in SLE in humans may not be commonly processed in this fashion, or alternatively, that the discrete electron-dense deposits are processed and undergo lysis within the glomerular mesangial regions before they are transported to the extraglomerular mesangial regions of the JGA.

Long-term survival after bone marrow transplantation: a 15-year follow-up report of a patient with Wiskott-Aldrich syndrome.

In 1968 a 2-year-old boy with Wiskott-Aldrich syndrome was extremely ill with eczema, a series of life-threatening infections, and repeated hemorrhages into his skin, lungs, brain, and other internal organs. He was given high-dose cyclophosphamide therapy for immunosuppression, followed by bone marrow cells from his histocompatible, healthy sister. In the 15 years since bone marrow transplantation, he has had full T cell, partial B cell, and no hematopoietic engraftment. He has weathered the usual infectious diseases of childhood, has had no serious infections, and despite persistent thrombocytopenia has not had serious bleeding episodes.

Therapeutic apheresis.

Therapeutic applications using semiautomated blood cell separators have improved the clinical management of several disorders through cellular or plasma depletion, or by rapid erythrocyte or plasma replacement. Cytapheresis procedures may remove large numbers of platelets or leukocytes in proliferative disorders, or induce and maintain a lymphopenia in "autoimmune" diseases. Rapid reductions in circulating paraproteins, autoantibodies, and immune complexes can be achieved to augment longer-term cytotoxic or immunosuppressive therapy. Therapeutic apheresis is adjunctive or palliative, not curative, and is usually short-term rather than chronic. Familiarity with the evolving indications for intervention with apheresis is essential for maximal benefit and minimal risk to the patients recommended for therapy.

Generalized morphoea successfully treated with salazopyrine.

A patient with active, generalized morphoea was treated successfully with salazopyrine on two occasions. The first time the trunk was involved and most of the skin softened after the drug therapy was started. After salazopyrine was discontinued, morphoea developed in the thighs but recommencement of therapy resulted in complete resolution.

Malignant clear cell hidradenoma: a case report.

A 73-year-old man developed a malignant clear cell hidradenoma on the nose. Although it was treated solely with diathermy and curettage it did not recur. These rare tumours are histologically malignant but do not always behave aggressively. In some patients local growth and recurrence may occur, while in others the tumour metastasizes widely. There is no way of predicting how these tumours will behave.

Thrombotic thrombocytopenic purpura and dose of plasma exchange.

Four patients with thrombotic thrombocytopenic purpura (TTP) were treated by plasma-exchange transfusion, three of whom recovered completely. Because previous reports in the literature describing exchange transfusion as treatment for TTP have demonstrated variable success rates, particular attention was given to "dose" and frequency of plasma exchange. Evans blue dye studies established a measure of "dose" under conditions of varying efficiency. Serum LDH activity was found to be diminished by plasma exchange, and the rate of return of serum LDH activity reflected residual disease activity. The magnitude of LDH activity reduction correlated with the adequacy of dose of plasma exchange and was an indicator for the need of repeated daily exchanges. Failure to obtain a spontaneous increment in platelet count also suggested the need for additional exchanges and/or larger dose of exchange. There is a need for a standard expression of dose of plasma exchange. Utilizing these markers (LDH, platelet count), it may be possible to improve the survival in TTP if adequate dose and frequency of plasma exchange are used.

Comparison of acid phosphatase isoenzymes of human seminal fluid, prostate, and leukocytes.

We used ion-exchange column chromatography and electrophoresis on polyacrylamide gel to compare the acid phosphatase isoenzymes of prostate and leukocytes. The major isoenzyme of the prostate is band 2A; only a trace of band 2B was observed. However, the major isoenzymes of leukocytes are band 4 and band 2B, and only a small amount of band 2A was observed. The three isoenzymes isolated from leukocytes or prostate gland react to the antiserum prepared against the aicd phosphatase isoenzyme of seminal fluid. Acid phosphatases of leukocytes other than the three isoenzymes mentioned above did not interact with the antiserum.

Biochemical characterization of an aryl acetic ester hydrolase isolated from human monocytes.

A carboxylic-ester hydrolase was isolated from the leukocytes of a patient with myelomonocytic leukemia. Its relative molecular mass as estimated by sucrose density-gradient sedimentation is about 70 000. The purified enzyme is specific for acetyl esters of aromatic alcohols. It is inhibited by fluoride, but insensitive to eserine or p-chloromercuriphenylsulfonate. Hydrolysis of 1-naphthyl acetate was optimal above pH 6.0; of o-nitrophenyl acetate, above 8.0. The common catalytic site for the two types of substrates on the enzyme was confirmed by competitive inhibition data.

Plateletpheresis in the management of thrombocytosis.

Acute thrombotic and hemorrhagic manifestations of thrombocytosis associated with myeloproliferative disorders may be life threatening. Conventional therapy with radioisotopes and/or cytotoxic drugs may require weeks for effective control of platelet counts. In five patients, plateletpheresis by discontinuous-flow (Haemonetics) or continuous-flow (Aminco Celltrifuge) centrifugation was used as a means of reducing platelet counts acutely. With each procedure, approximately 2-9 X 10(12) platelets were removed, resulting in decrements in platelet counts and relief of symptoms. Plateletpheresis is a useful and safe acute means of controlling platelet counts in myeloproliferative disorders.