Improving outcomes in patients with Acute Kidney Injury: the impact of hospital based automated AKI alerts.

BACKGROUND: Acute kidney injury (AKI) is a significant cause of morbidity and mortality. Early identification may improve the outcome and in 2012 our hospital introduced an automated AKI alert system for early detection and management of AKI. OBJECTIVES: Using an automated AKI alert system we analysed whether early review and intervention by the Critical Care and Outreach (CCOT) team improved patient outcomes in AKI and whether serum bicarbonate was useful in predicting outcomes in patients with AKI. METHODS: In a retrospective analysis we identified patients who triggered an AKI alert from 20 April 2012 to 20 September 2013 and collected data on mortality, length of stay, need for intensive care admission and renal replacement therapy (RRT). RESULTS: 994 AKI alerts were generated and analysed. Patients with bicarbonate outside the normal range had significantly higher mortality. Bicarbonate <22 mmol/L was associated with a mortality of 25.7% (49/191) compared with 16.9% (39/231) when 22-29 mmol/L (p=0.047, χ(2)). Those patients reviewed ≥1 day after AKI alert by CCOT compared with those seen on the day of the alert had a 2.4 times increase in mortality and were 7 times more likely to require RRT acutely. CONCLUSIONS: Electronically identified AKI alerts identify patients at high risk of morbidity and mortality. In this group AKI alerts preceded CCOT review by a mean of 2 days. This represents a window for supportive interventions, which may explain improved outcomes in those reviewed earlier. The addition of serum bicarbonate offers a further method of risk stratifying patients at greater risk of death.

Near-hanging as presenting to hospitals in Queensland: recommendations for practice.

Near-hanging is an increasing presentation to hospitals in Australasia. We reviewed the clinical management and outcome of these patients as they presented to public hospitals in Queensland. A retrospective clinical record audit was made at five public hospitals between 1991 and 2000. Of 161 patients enrolled, 82% were male, 8% were indigenous and 10% had made a previous hanging attempt. Chronic medical illnesses were documented in 11% and previous psychiatric disorders in 42%. Of the 38 patients with a Glasgow Coma Scale score (GCS) of 3 on arrival at hospital, 32% returned to independent living and 63% died. Fifty-two patients received CPR, of whom 46% had an independent functional outcome. Independent predictors of mortality were a GCS on hospital arrival of 3 (AOR 150, CI 95% 12.4-1818, P<0.001), taking plain X-rays of the cervical spine (AOR 0.06, CI 95% 0.004-0.97, P=0.047) and contact with the ground (AOR 0.03, CI 95% 0.002-0.62, P=0.02). Only 66% had imaging of the cervical spine performed with other imaging performed infrequently. There were three laryngeal, two hyoid bone and three cervical spine injuries and one carotid dissection. The number of cervical spine X-rays required to find a significant cervical spine fracture was 54. Near-hanging presenting to hospital with a poor conscious state or even cardiac arrest can have a favourable clinical outcome. Radiological investigations are infrequently performed despite a low GCS precluding early accurate assessment. Given the general favourable outcome, an aggressive approach to searching for correctable injuries is recommended.

Abnormal cervical cytology: a risk factor for endometrial cancer recurrence.

The objective of this study was to evaluate the relationship between cervical cytology, histologic type, and risk of endometrial cancer recurrence. We performed a retrospective study of patients undergoing surgery for endometrial carcinoma. Risk factors for recurrence including histology, tumor grade, nodal status, myometrial invasion, peritoneal washings, stage, and cervical cytology were assessed. Abnormal cervical cytology was defined as the presence of any endometrial cells on Pap smear. Papillary serous and clear cell carcinomas were considered high-risk histologies. Univariate and multivariate analyses of risk factors for recurrence were performed. Thirty-nine (9%) patients developed recurrent endometrial cancer. More patients with abnormal Pap smears recurred (12% versus 4%, P < 0.05). For endometrioid adenocarcinoma, abnormal cervical cytology occurred in 61% and 7% recurred, while with high-risk histologies, 84% had abnormal cervical cytology and 19% recurred (P < 0.05). Other significant predictors of recurrence on univariate analysis were myometrial invasion, nodal status, washings, stage, and histology. On multivariate analysis, only nodal status remained a significant predictor of recurrence. Abnormal cervical cytology is associated with increased risk of endometrial cancer recurrence. Abnormal cervical cytology occurs more frequently in high-risk histologies, which are known to have a higher risk of recurrence. On multivariate analysis, only nodal spread remains a significant predictor of recurrence.

Practical and dosimetric implications of a new type of packaging for radiographic film.

Recently, Kodak introduced new light-tight packages (vacuum packaging, aluminium layer under black polyethylene and different paper) for their oncology films (EDR-2, X-Omat V and PPL-2). In order to avoid additional uncertainty and to ensure transferability of previously published results, we assessed in this study the effect of the old and new packages on the dosimetric response of EDR-2 radiographic film. Therefore, sensitometric measurements were performed for different film assemblies (new envelope + new paper, old envelope + old paper, new envelope without paper and old envelope without paper). In addition, to assess possible effects of the package on the film depth-dose response, packaged films were irradiated in parallel geometry, and central depth-dose curves were retrieved. For the perpendicular geometry, on the other hand, the effect of the package was assessed at large depth for a high intensity-modulated inverse-pyramid beam. The results of the sensitometric measurements reveal no difference between the packages. However, the white colour of the paper in both the packages induces a dose-dependent increase in optical density (0-0.12) of the film. The depth-dose curves show better reproducibility for the new package and the new paper improves the accuracy of film dosimetry, but despite the company's effort to evacuate the air out of the new envelope, it remains necessary to clamp the films in the phantom for the parallel irradiation geometry. At 5 cm depth, the films irradiated in parallel geometry show an under-response of 3-5% compared to films irradiated perpendicularly. Finally, even at locations of large photon scatter, no filtration effect from the aluminium layer incorporated in the new envelope has been observed for perpendicular irradiation geometry.

[Hepatic and hematological complications following ecstasy usage].

"Ecstasy" (3,4-Methylenedioxymethamphetamine), is used as a mood enhancer. We describe a case of a 23 year-old male suffering from thrombotic thrombocytopenic purpura (TTP), and severe hepatitis following ingestion of ecstasy. We describe the various hepatic complications, including hepatitis, cirrhosis, and hepatic failure, in addition to the hematological complications including DIC and TTP secondary to ecstasy abuse. Ecstasy abuse should be considered in every patient with unexplained hepatic or hematologic complications.

Vascular access via peripherally inserted central venous catheters (PICCs): experience in 40 patients with acute myeloid leukemia at a single institute.

Reliable long-term vascular access is essential for the treatment of patients with acute myeloid leukemia (AML). Although peripherally inserted central catheters (PICCs) have been in use for many years, little data exist on their use in patients receiving intensive chemotherapy. We retrospectively reviewed all AML patients who had a PICC inserted between July 95 and May 98. Fifty two PICCs were inserted in 40 patients with AML. Thirty three PICCs were inserted during severe thrombocytopenia (platelets < 50 x 10(9)/L), and 31 during severe neutropenia (neutrophils < 0.5 x 10(9)/L). Mean catheter duration was 82 (median 63, range 3-441) days for a total of 4274 catheter days. A mean of 1.8 chemotherapy courses were administered via each PICC. There were 5 early complications of PICC placement. Other mechanical complications occurred in 14 catheters and phlebitis in 12. Twenty blood stream infections (BSI) occurred in 17 patients. All BSIs occurred during neutropenia. Seventeen PICCs were removed due to the following complications - phlebitis (11), possible catheter related BSI (4), mechanical reasons in 3 (2 with concomitant phlebitis) and persistent fever (1). PICC duration was significantly shorter in these 17 catheters (52.9 v 96.4 days in the other 35, p=0.0289). We conclude that PICCs provide long-term vascular access with an acceptable complication rate in patients with AML. However, a randomised trial is required before PICCs can be considered an alternative to tunneled central venous catheters in these patients.

Mutation in the methylenetetrahydrofolate reductase gene might be a risk factor for cerebrovascular disease in peripartum and under oral contraceptive use.

Nine women (age 22-43 years) with cerebrovascular diseases (CVD) related to pregnancy, puerperium or contraceptive use were studied. Five were pregnant, 2 were post partum and 2 were taking oral contraceptives. All under- went a complete etiological examination including assessment for the thermolabile C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene mutation. Three of the 9 patients were homozygotic for the C677T MTHFR mutation, and 3 were heterozygotic. In these 6 patients, no other etiology could be found. Mutation in the thermolabile MTHFR gene might be an important cause for CVD related to peripartum or contraceptive use.

Unexpectedly high incidence of hypoplastic/aplastic foci in bone marrow biopsies of hairy cell leukemia patients in remission following 2-chlorodeoxyadenosine therapy.

Treatment with the purine analog 2-chlorodeoxyadenosine (2-CDA) achieves a complete response in close to 90% of patients with hairy cell leukemia, with approximately 75% remaining in prolonged remission. Recently, we unexpectedly noted foci of hypoplasia and aplasia in routine follow-up bone marrow biopsies of several hairy cell leukemia patients in remission with normal blood counts. Because of this finding we examined all available biopsies to assess the incidence of this phenomenon. A total of 94 biopsies in 31 patients were reviewed. Of these, 23 were prior to 2-CDA therapy and 71 (in 30 patients) were obtained 2-76 (mean 22) months following one or more courses of treatment. Nine patients had also received prior interferon and 7 (of whom 3 had also received interferon) had undergone splenectomy. Hypocellular foci were found in only 3 (13%) of the pre-therapy biopsies. Forty-seven of the 71 post-therapy biopsies (in 23 patients) (66%) had a total of 176 hypocellular foci. Of these 47 biopsies, 39 were without evidence of disease. A simultaneous complete blood count was normal in 34 of the 47 hypoplastic biopsies (72%). This suggests that these hypoplastic areas may not be representative of the entire bone marrow and that normal hematopoiesis may take place at other sites. However, since the longest follow-up is less than 7 yr, the potential long-term significance of these findings, such as progressive bone marrow aplasia or dysplasia, may still be unrecognised.

Root infinitives in Dutch early child language: an effect of input?

Children who acquire Dutch as their first language show a strong preference for using infinitival verb forms during the early stages of grammatical development. This exemplifies the 'root infinitive' (RI) phenomenon, which has played a significant role in recent discussions on the development of syntax. Most accounts proposed thus far invoke an immaturity of the child's grammatical competence. We explore the possibility that the early predominance of infinitival forms is related to patterns in the language input. We analysed a corpus of utterances addressed by two Dutch-speaking mothers to their two- to three-year old sons. Root infinitive utterances amounted to 10%, and auxiliary-plus infinitive main verb constructions, which in terms of word order are maximally similar to RIs, constituted 30% of all verb-containing utterances. These figures render an account in terms of exposure to utterance structures unlikely. There is a moderate (but significant) correlation between frequency of occurrence of individual verb forms in the input and age of acquisition. However, infinitive verb forms are often acquired earlier than their input frequency would predict, and this may be related to an overall increased salience, due to their systematic appearance in sentence-final position and their relatively high conceptual transparency as compared to finite verbs.

CT-guided core-needle biopsy in the diagnosis of mediastinal lymphoma.

The advent of radiologic guidance techniques for percutaneous biopsy has changed the approach to the routine diagnosis of mediastinal lymphoma. The aim of the present study was to evaluate the diagnostic accuracy of CT-guided percutaneous core-needle biopsy (PCNB) in the clinical management of patients with mediastinal lymphoma. The results of 49 CT-guided PCNB of mediastinal lymphoma performed under local anesthesia in 42 ambulatory patients were analyzed. A positive diagnosis of lymphoma was obtained in 30 of 42 patients, with an overall success rate of 71.5%. The technique was equally successful in the diagnosis of Hodgkin's and non-Hodgkin's lymphoma. There were no major complications. Percutaneous CT-guided CNB of mediastinal lymphoma is a quick, safe, accurate, and efficient alternative to open biopsy in the evaluation of mediastinal lymphoma, mainly at presentation. It should become the preferred initial diagnostic procedure for obtaining histologic samples in patients with suspected mediastinal lymphoma.

Programs for the development of physician leaders: a curricular process in its infancy.

Physician leaders are crucial as never before to ensure the proper integration of good care and cost containment; such integration is both a reasonable expectation of patients and essential for the survival of health care delivery systems. In today's health care environment, a critical mass of physician leaders must be developed in a systematic fashion so that physicians may truly lead the health care enterprise. The authors (1) describe, with examples, the various types and levels of physician leadership training programs currently being offered; (2) explain the costs and benefits of each program type; and (3) offer a program rationale and model (using a program at their medical school), which they analyze using traditional management concepts such as strategic planning, net present value, and make-versus-buy. The authors emphasize that physician leadership training should be local, offer long-term instruction, and be led by physicians. They conclude by stating that the concept of physician leadership will not and should not be taken seriously by non-physician health care executives until the physician community becomes as serious about leadership and management training as it is about clinical training.

Severe thrombotic complications associated with activated protein C resistance acquired by orthotopic liver transplantation.

We report a patient who developed recurrent hepatic artery thrombosis and deep venous thrombosis following orthotopic liver transplantation. Investigations revealed the presence of activated protein C (APC) resistance due to a mutation in the factor V gene in the transplanted liver. The patient's own peripheral blood cells did not carry the mutation. Although part of factor V is located in the platelets and may be endogenously synthesized by megakaryocytes, this case demonstrates the major clinical importance of hepatic-derived factor V. It may be reasonable to screen liver donors with a history of a thrombotic event for APC, and to consider anticoagulation in the recipients of livers positive for this defect.

A chronic hypercoagulable state in patients with beta-thalassaemia major is already present in childhood.

A higher than normal incidence of thromboembolic events has been observed in adult patients with beta-thalassaemia major (TM) and certain haemostatic anomalies found in these patients suggest the existence of a chronic hypercoagulable state. Thalassaemic red blood cells (RBC) were demonstrated to facilitate thrombin formation due to altered asymmetry of the membrane phospholipids with enhanced exposure of phosphatidylserine. Since RBC anomalies exist in thalassaemia from the first months of life, we studied markers of hypercoagulability and thrombophilia in 36 adult patients (range 19-38 years) and 26 children (range 2-18 years) with beta-TM. All the patients were in steady state and none had experienced clinical signs or symptoms of thrombosis. Highly elevated urinary levels of 11-dehydro-thromboxane B2 and significantly elevated plasma levels of thrombin-antithrombin III (TAT) complexes were observed to the same extent in TM children and adults. The levels of factor II were decreased while factors V, VII + X and plasminogen were within the normal range. The natural coagulation inhibitors, protein C (PC) and protein S (PS) were significantly decreased in all TM patients investigated, regardless of age, but the PS binding protein (C4bBP) and antithrombin III levels were normal. The frequency of other thrombophilic mutations was not increased. Thus, a chronic hypercoagulable state already exists in thalassaemia in childhood and may contribute to the cardiac and pulmonary anomalies and the thrombotic events which occur later.

The effect of enoxaparin on bleomycin-induced lung injury in mice.

We have evaluated the effect of enoxaparin, a potent antithrombotic drug, on bleomycin (Bleo)-induced pulmonary inflammation in mice. Pulmonary injury was induced by a single intratracheal (i.t.) instillation of Bleo. Four groups of female C57BL/6 mice, each received one of four treatments: (1) i.t. Bleo and daily intraperitoneal (i.p.) injections of enoxaparin (EN) starting one day before i.t. instillation of Bleo (Bleo-EN); (2) i.t. Bleo and i.p. injections of saline (Bleo-Sal); (3) i.t. saline and i.p. enoxaparin (Sal-EN); (4) i.t. saline and i.p. saline (Sal-Sal). Animals were sacrificed 14 days after i.t. treatment. Lung injury was evaluated by analysis of bronchoalveolar lavage fluid and histologically by an overall semiquantitative index of lung injury and a quantitative image analysis assessing alveolar wall area fraction and fibrosis fraction. Treatment of mice with enoxaparin did not ameliorate Bleo-induced lung injury. Our study does not establish a critical role of procoagulant activity in the evolution of Bleo-induced lung injury and does not support the use of antithrombotic therapy for the prevention of pulmonary fibrosis.

Salvage therapy of refractory and relapsed acute leukemia with high dose mitoxantrone and high dose cytarabine.

We have assessed the outcome of 66 refractory and relapsed acute leukemia patients treated with high dose mitoxantrone and cytarabine. Therapy consisted of a total dose of 40-60 mg/m2 mitoxantrone and 3 g/m2 of cytarabine daily on 5 consecutive days. A total of 28 patients were treated for primary resistant and 38 patients for early or late relapsed leukemia. A total of 35 patients achieved CR. Four patients died during the induction course. Toxicity was acceptable and comparable to other salvage regimens. The median disease-free and overall survivals were 4 and 6 months, respectively. Although this regimen is effective in achieving remission in refractory leukemia, its duration is short.

Platelet function abnormalities in Gaucher disease patients.

Bleeding manifestations are common in Gaucher disease patients. Although usually attributed to thrombocytopenia, some patients with relatively high platelet counts and normal coagulation tests have hemorrhagic phenomena. To investigate whether perturbed platelet function could explain these bleeding manifestations we performed platelet aggregation tests on 32 type I adult Gaucher patients who were not severely thrombocytopenic (platelet counts >50 x 10(9)/L). Seven patients (22%) had abnormal platelet aggregation. In five, platelet aggregation was markedly reduced in response to collagen and ADP and virtually absent in response to epinephrine, whereas two patients had isolated severely impaired epinephrine-induced aggregation. In one patient platelet aggregation markedly improved following one year of enzyme replacement therapy. Incubating normal platelets with high concentrations of glucocerebroside did not impair their ability to aggregate, suggesting that plasma glucocerebroside does not directly interfere with platelet function. Platelet dysfunction is a hitherto unrecognised, relatively common cause of excessive bleeding in Gaucher patients.

Treatment of hairy-cell leukemia: current views.

Although hairy-cell leukemia (HCL) is uncommon, remarkable progress has been made in the treatment of patients with this disease. Because of their unique mechanisms of action, the purine analogs, 2'-deoxycoformycin (2'-DCF) and 2-chlorodeoxyadenosine (2-CdA), are naturally targeted to lymphocytes and are cytotoxic to both resting and dividing cells. Both of these agents induce durable complete remissions (CRs) in the overwhelming majority of patients. Remarkably, equally high rates of durable CR are achieved in both untreated and previously treated patients. Furthermore, patients with large tumor burdens fare as well as those with minimal disease. Therefore, these agents have emerged as the treatments of choice for all patients with hairy-cell leukemia and have supplanted earlier treatments such as splenectomy and interferon-alpha (IFN-alpha). Since a single 7-day cycle of 2-CdA leads to excellent outcomes and is associated with few toxicities other than culture-negative fever, this agent is particularly attractive and may offer some advantages. However, given the indolent natural history of HCL, long-term follow-up study will be required to determine if one purine analog offers a survival advantage over the other.