Rivaroxaban Versus Warfarin and Risk of Post-Thrombotic Syndrome Among Patients with Venous Thromboembolism

Background

The effectiveness of rivaroxaban to reduce post-thrombotic syndrome in patients with venous thromboembolism is largely unknown. We compared rates of post-thrombotic syndrome in patients given rivaroxaban versus warfarin in a cohort of patients with incident venous thromboembolism receiving routine clinical care.

Arterial cardiovascular risk factors and venous thrombosis: results from a population-based, prospective study (the HUNT 2)

Background

An explanation for the increased risk of myocardial infarction and stroke in patients with venous thrombosis is lacking. The objective of this study was to investigate whether risk factors for arterial cardiovascular disease also increase the risk of venous thrombosis.

Design and Methods

Cases who had a first venous thrombosis (n=515) and matched controls (n=1,505) were identified from a population-based, nested, case-cohort study (the HUNT 2 study) comprising 71% (n=66,140) of the adult residents of Nord-Trøndelag County in Norway.

Results

The age- and sex-adjusted odds ratio of venous thrombosis for subjects with concentrations of C-reactive protein in the highest quintile was 1.6 (95% confidence interval: 1.2–2.2) compared to subjects with C-reactive protein in the lowest quintile. This association was strongest in subjects who experienced venous thrombosis within a year after blood sampling with a three-fold increased risk of participants in the highest versus the lowest quintile. Having first degree relatives who had a myocardial infarction before the age of 60 years was positively associated with venous thrombosis compared to not having a positive family history [odds ratio 1.3 (95% confidence interval: 1.1–1.6)]. Subjects with blood pressure in the highest quintile had half the risk of developing venous thrombosis compared to subjects whose blood pressure was in the lowest quintile. There were no associations between the risk of venous thrombosis and total cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol, triglycerides, glucose or smoking. We confirmed the positive association between obesity and venous thrombosis.

Conclusions

C-reactive protein and a family history of myocardial infarction were positively associated with subsequent venous thrombosis. Blood pressure was inversely correlated to venous thrombosis. These findings should be confirmed by further investigations.     

Thrombolytic therapy is effective in paroxysmal nocturnal hemoglobinuria: a series of nine patients and a review of the literature

Background

Thrombosis is the major risk factor for death in patients with paroxysmal nocturnal hemoglobinuria. Previous case reports indicate that venous thrombosis in patients with paroxysmal nocturnal hemoglobinuria is amenable to thrombolysis.

Design and Methods

We reviewed the outcome of thrombolytic therapy for patients with paroxysmal nocturnal hemoglobinuria who had thromboses refractory to anticoagulation at our institutions.

Results

In this study of 41 patients who had at least one thrombotic event, we confirmed a very high incidence of recurrence despite anticoagulation. Nine patients with thrombosis were regarded as eligible for administration of intravenous tissue plasminogen activator, which was effective in reversing thrombi in all of 15 occasions in which it was given. Serious hemorrhagic complications developed in three cases. At last follow-up visit, of the nine patients treated, three had died, and six were in very good to excellent condition in terms of clinical outcome and radiological findings. The only patient in whom thrombolysis may have contributed to a fatal outcome also had complications of “heparin induced thrombocytopenia with thrombosis”, which we diagnosed in three additional patients. In our review of the literature, nine out of 15 patients treated with thrombolysis have had a good outcome.

Conclusions

Although it is associated with a significant but manageable risk of bleeding, systemic thrombolysis is a highly effective treatment for reversing venous thromboses in patients with paroxysmal nocturnal hemoglobinuria.     

Long-term low-molecular-weight heparin and the post-thrombotic syndrome: a systematic review

Objective

Post-thrombotic syndrome causes considerable morbidity. The Home-LITE study showed a lower incidence of post-thrombotic syndrome and venous ulcers after 3 months of treating deep vein thrombosis with the low-molecular-weight heparin tinzaparin versus oral anticoagulation. This systematic review examined whether long-term treatment of deep vein thrombosis using low-molecular-weight heparin, rather than oral anticoagulation, reduces development of post-thrombotic syndrome.

Methods

We identified 9 articles comparing treatment of deep vein thrombosis using long-term low-molecular-weight heparin with any comparator, which reported outcomes relevant to the post-thrombotic syndrome assessed ≥ 3 months post-deep vein thrombosis.

Results

Pooled analysis of 2 studies yielded an 87% risk reduction with low-molecular-weight heparin in the incidence of venous ulcers at ≥ 3 months (P = .019). One study showed an overall odds ratio of 0.77 (P = .001) favoring low-molecular-weight heparin for the presence of 8 patient-reported post-thrombotic syndrome signs and symptoms. Pooled analysis of 5 studies showed a risk ratio for low-molecular-weight heparin versus oral anticoagulation of 0.66 (P < .0001) for complete recanalization of thrombosed veins.

Conclusion

These results support the lower incidence of post-thrombotic syndrome and venous ulcers observed in Home-LITE. Long-term treatment with low-molecular-weight heparin rather than oral anticoagulation after a deep vein thrombosis may reduce or prevent development of signs and symptoms associated with post-thrombotic syndrome. Post-thrombotic syndrome and associated acute ulcers may develop more rapidly after deep vein thrombosis than previously recognized.     

Erythropoiesis-stimulating agents are not associated with increased risk of thrombosis in patients with myelodysplastic syndromes

Background

There are limited reports of thrombosis among myelodysplastic syndrome patients exposed to erythropoiesis stimulating agents. It is not clear whether erythropoiesis stimulating agents are associated with an increased risk of thrombosis in myelodysplastic syndromes, as they are among patients with solid tumors.

Design and Methods

The association between use of erythropoiesis stimulating agent and transient thrombosis risk in patients with myelodysplastic syndromes was assessed in a case-crossover study nested within a cohort of incident myelodysplastic syndrome patients. Using the US Surveillance, Epidemiology, and End Results Medicare-linked database, cases with an incident diagnosis of deep vein thrombosis were identified. Using conditional logistical regression, the odds of exposure to erythropoiesis stimulating agents in the 12 weeks prior to the incident deep vein thrombosis (hazard period) was compared to the exposure odds in a prior 12-week comparison period.

Results

Within the cohort of eligibles with myelodysplastic syndromes (n=5,673) there were 212 incident cases of deep vein thrombosis events. Mean age was 76.2 (standard deviation=±8.6) years. Use of erythropoiesis stimulating agents was not associated with deep vein thrombosis in the crude nor the adjusted models (OR=1.21, 95% CI: 0.60, 2.43). Central venous catheter placement (OR=6.47, 95% CI: 2.37, 17.62) and red blood cell transfusion (OR=4.60, 95% CI: 2.29, 9.23) were associated with deep vein thrombosis.

Conclusions

Despite the link between use of erythropoiesis stimulating agents and thrombosis among patients with solid tumors, this study provides evidence that their safety profile may be different among patients with myelodysplastic syndromes.     

Thrombectomy reduces the systemic complications in device-related right atrial septic thrombosis

BACKGROUND:

Septic thrombosis of the right atrium is an unusual complication associated with the use of indwelling devices. The optimal management of this condition is unclear. Our experience with a patient with hemodialysis catheter-related septic thrombosis of the right atrium illustrates the difficulties associated with this condition.

OBJECTIVES:

To determine the effects of surgical thrombectomy compared with nonsurgical treatment with antibiotics (with or without anticoagulation) on mortality rates and complications in patients with device-related septic thrombosis of the right atrium.

METHODS:

A retrospective analysis of all reported cases of device-related right heart septic thrombosis in which therapy and outcome were reported was conducted using a PubMed search in the English-language literature (1985 to 2006).

RESULTS:

Forty cases of device-related right atrial septic thromboses were reported in the literature during the chosen time period. The treatments administered were none (12.5%), antibiotics (12.5%), antibiotics and anticoagulation (20%), and thrombectomy (55%). The mean clot size was significantly larger in patients who underwent thrombectomy. All untreated patients died. Excluding the untreated patients from the analysis, systemic complications were significantly lower in the thrombectomy group than in the groups receiving nonsurgical therapies. Using multivariate modelling with survival as the primary outcome, age, sex, clot size, clot location, microbial organism or type of treatment were not predictive of the outcome.

CONCLUSION:

Device-related right atrial septic thrombosis is associated with significant mortality and is uniformly fatal if untreated. Surgical thrombectomy is associated with less frequent systemic complications. A well-designed prospective, randomized trial is needed to determine the optimal treatment of this condition.     

Impact of the degree of anemia on the outcome of patients with myelodysplastic syndrome and its integration into the WHO classification-based Prognostic Scoring System (WPSS)

Background

Anemia is an established negative prognostic factor in myelodysplastic syndromes but the relationship between its degree and clinical outcome is poorly defined. We, therefore, studied the relationship between severity of anemia and outcome in myelodysplastic syndrome patients.

Design and Methods

We studied 840 consecutive patients diagnosed with myelodysplastic syndromes at the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, and 504 patients seen at the Heinrich-Heine-University Hospital, Düsseldorf, Germany. Hemoglobin levels were monitored longitudinally and analyzed by means of time-dependent Cox’s proportional hazards regression models.

Results

Hemoglobin levels lower than 9 g/dL in males (HR 5.56, P=0.018) and 8 g/dL in females (HR=5.35, P=0.026) were independently related to reduced overall survival, higher risk of non-leukemic death and cardiac death (P<0.001). Severe anemia, defined as hemoglobin below these thresholds, was found to be as effective as transfusion-dependency in the prognostic assessment. After integrating this definition of severe anemia into the WHO classification-based Prognostic Scoring System, time-dependent regression and landmark analyses showed that the refined model was able to identify risk groups with different survivals at any time during follow up.

Conclusions

Accounting for severity of anemia through the WHO classification-based Prognostic Scoring System provides an objective criterion for prognostic assessment and implementation of risk-adapted treatment strategies in myelodysplastic syndrome patients.     

General anesthetic versus light sedation: Effect on pediatric endoscopy wait times

BACKGROUND:

Wait times are an important measure of health care system effectiveness. There are no studies describing wait times in pediatric gastroenterology for either outpatient visits or endoscopy. Pediatric endoscopy is performed under light sedation or general anesthesia. The latter is hypothesized to be associated with a longer wait time due to practical limits on access to anesthesia in the Canadian health care system.

OBJECTIVE:

To identify wait time differences according to sedation type and measure adverse clinical outcomes that may arise from increased wait time to endoscopy in pediatric patients.

METHODS:

The present study was a retrospective review of medical charts of all patients <18 years of age who had been assessed in the pediatric gastroenterology clinic and were scheduled for an elective outpatient endoscopic procedure at McMaster Children’s Hospital (Hamilton, Ontario) between January 2006 and December 2007. The primary outcome measure was time between clinic visit and date of endoscopy. Secondary outcome measures included other defined waiting periods and complications while waiting, such as emergency room visits and hospital admissions.

RESULTS:

The median wait time to procedure was 64 days for general anesthesia patients and 22 days for patients who underwent light sedation (P<0.0001). There was no significant difference between the two groups with regard to the number of emergency room visits or hospital admissions, both pre- and postendoscopy.

CONCLUSIONS:

Due to the lack of pediatric anesthetic resources, patients who were administered general anesthesia experienced a longer wait time for endoscopy compared with patients who underwent light sedation. This did not result in adverse clinical outcomes in this population.     

Effectiveness of two Arthritis Foundation programs: Walk With Ease,and YOU Can Break the Pain Cycle

Objective:

To evaluate the effectiveness of two Arthritis Foundation programs: Walk With Ease (WWE) and YOU Can Break The Pain Cycle (PC).

Design:

Quasi-experimental, repeated measures design. Retested at six weeks and four months.

Setting:

Community based intervention.

Participants:

Volunteer sample of 163 adults with arthritis recruited through mailings, newspapers, and flyers.

Interventions:

Subjects participated in a 90 minute seminar (PC, Group A), a six-week walking program (WWE, Group B), or both programs (Group C).

Main outcome measures:

Survey assessment of arthritis knowledge, general health, self-management activities, confidence, physical abilities, depression, health distress, and how arthritis affects their life. A Squat Test, a Six Minute Walk test, and a Timed Functional Walk Test were also administered.

Results:

Subjects in Group B were more confident, less depressed, had less health distress, and less pain than subjects in Group A. Scores of Group C were between Group A and B scores. Differences in groups over time indicated that the WWE resulted in increased confidence, physical abilities, time spent in self-management activities and decreased pain and fatigue. All groups increased in walking endurance at six weeks, and increased in health distress at four months.

Conclusion:

Subjects in different programs differed on impact of arthritis. These programs provide effective arthritis management opportunities.     

Point-of-care, peer-comparator colonoscopy practice audit: The Canadian Association of Gastroenterology Quality Program--Endoscopy

BACKGROUND

Point-of-care practice audits allow documentation of procedural outcomes to support quality improvement in endoscopic practice.

OBJECTIVE

To evaluate a colonoscopists’ practice audit tool that provides point-of-care data collection and peer-comparator feedback.

METHODS

A prospective, observational colonoscopy practice audit was conducted in academic and community endoscopy units for unselected patients undergoing colonoscopy. Anonymized colonoscopist, patient and practice data were collected using touchscreen smart-phones with automated data upload for data analysis and review by participants. The main outcome measures were the following colonoscopy quality indicators: colonoscope insertion and withdrawal times, bowel preparation quality, sedation, immediate complications and polypectomy, and biopsy rates.

RESULTS

Over a span of 16 months, 62 endoscopists reported on 1279 colonoscopy procedures. The mean cecal intubation rate was 94.9% (10th centile 84.2%). The mean withdrawal time was 8.8 min and, for nonpolypectomy colonoscopies, 41.9% of colonoscopists reported a mean withdrawal time of less than 6 min. Polypectomy was performed in 37% of colonoscopies. Independent predictors of polypectomy included the following: endoscopy unit type, patient age, interval since previous colonoscopy, bowel preparation quality, stable inflammatory bowel disease, previous colon polyps and withdrawal time. Withdrawal times of less than 6 min were associated with lower polyp removal rates (mean difference −11.3% [95% CI −2.8% to −19.9%]; P=0.01).

DISCUSSION

Cecal intubation rates exceeded 90% and polypectomy rates exceeded 30%, but withdrawal times were frequently shorter than recommended. There are marked practice variations consistent with previous observations.

CONCLUSION

Real-time, point-of-care practice audits with prompt, confidential access to outcome data provide a basis for targeted educational programs to improve quality in colonoscopy practice.     

Diagnostic practices and disease surveillance in Canadian children with congenital central hypoventilation syndrome

OBJECTIVE:

To assess the diagnostic and surveillance practices of Canadian pediatric subspecialists for children with congenital central hypoventilation syndrome (CCHS).

METHODS:

The present analysis was a prospective cross-sectional study. A web-based survey was sent to 303 pediatric subspecialists in Canada: 85 pediatric respirologists, 77 pediatric neurologists and 141 neonatologists. The survey included 36 questions about the current diagnostic and surveillance management of pediatric CCHS. Differences in responses among respirologists, neurologists and neonatologists were evaluated for each question, where feasible, and responses were compared with the 2010 American Thoracic Society (ATS) Clinical Policy Statement for CCHS.

RESULTS:

A total of 83 (27%) participants responded to the survey; the highest survey response rate (40%) was from respirologists. For the diagnosis of CCHS, 25% of respondents did not order genetic testing, either alone or with another test, to make a diagnosis of CCHS. The criteria and tests recommended by the ATS to make a diagnosis of CCHS – genetic testing, diagnosis of exclusion, polysomnogram and plus or minus a hypercapnic challenge – were ordered by 23 (43%) of the 54 respondents. Although polysomnograms were ordered for more than 90% of children with CCHS, only 37% of respirologists aimed for a carbon dioxide range of 35 mmHg to 40 mmHg during polysomnogram titrations.

CONCLUSIONS:

The results demonstrate variability in the diagnostic and surveillance practices of pediatric subspecialists in children with CCHS across Canada. The present study provides an initial needs assessment and demonstrated that there are significant deviations in practice from the 2010 ATS guidelines.     

Admission is not always necessary for patients with community-acquired pneumonia in risk classes IV and V diagnosed in the emergency room

OBJECTIVE:

To determine the factors that allow patients with community-acquired pneumonia who are at high risk of mortality (risk classes IV and V) to be treated at home.

DESIGN:

A prospective, observational study.

SETTING:

Six hospitals and one free-standing emergency room in Edmonton, Alberta.

PARTICIPANTS:

The present study included 2354 patients in risk classes IV and V who had a diagnosis of pneumonia made by an emergency room physician or an internist.

MEASUREMENTS:

Symptoms, signs and laboratory findings, as well as outcome measures of length of stay and mortality.

RESULTS:

Of the total study group, 319 of the patients (13.5%) were treated on an ambulatory basis. Factors predictive of admission were definite or possible pneumonia on chest radiograph as read by a radiologist, functional impairment, altered mental status, substance abuse, psychiatric disorder, abnormal white blood cell count, abnormal lymphocyte count, oxygen saturation less than 90% and antibiotic administration in the week before admission. If chest pain was present, admission was less likely. Only two of the 319 patients required subsequent admission (both had positive blood cultures) and only two died.

CONCLUSIONS:

A substantial number of patients in risk classes IV and V can be safely treated at home. Factors that help clinicians to select this subset of patients are discussed.     

Chronic Care Model Decision Support and Clinical Information Systems Interventions for People Living with HIV: A Systematic Review

BACKGROUND

The Chronic Care Model is an effective framework for improving chronic disease management. There is scarce literature describing this model for people living with HIV. Decision Support (DS) and Clinical Information Systems (CIS) are two components of this model that aim to improve care by changing health care provider behavior.

OBJECTIVE

Our aim was to assess the effectiveness of DS and CIS interventions for individuals with HIV, through a systematic literature review.

DESIGN

We performed systematic electronic searches from 1996 to February 2011 of the medical (E.g. Medline, EMBASE, CINAHL) and grey literature. Effectiveness was measured by the frequency of statistically significant outcome improvement. Data and key equity indicator extraction and synthesis was completed.

PARTICIPANTS AND INTERVENTIONS

We included comparative studies of people living with HIV that examined the impact of DS or CIS interventions on outcomes.

MAIN MEASURES

The following measures were assessed: outcome (immunological/virological, medical, psychosocial, economic measures) and health care process/performance measures.

KEY RESULTS

Records were screened for relevance (n = 10,169), full-text copies of relevant studies were obtained (n = 123), and 16 studies were included in the review. Overall, 5/9 (55.6%) and 17/41 (41.5%) process measures and 5/12 (41.7%) and 3/9 (33.3%) outcome measures for DS and CIS interventions, respectively, were statistically significantly improved. DS–explicit mention of implementation of guidelines and CIS-reminders showed the most frequent improvement in outcomes. DS-only interventions were more effective than CIS-only interventions in improving both process and outcome measures. Clinical, statistical and methodological heterogeneity among studies precluded meta-analysis. Primary studies were methodologically weak and often included multifaceted interventions that made assessment of effectiveness challenging.

CONCLUSIONS

Overall, DS and CIS interventions may modestly improve care for people living with HIV, having a greater impact on process measures compared to outcome measures. These interventions should be considered as part of strategies to improve HIV care through changing provider performance.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-012-2145-y) contains supplementary material, which is available to authorized users.KEY Words: HIV/AIDS, chronic disease management, Chronic Care Model, decision support, clinical information systems, practice guidelines, systematic review     

AKI in Children Hospitalized with Nephrotic Syndrome

Background and objectives

Children with nephrotic syndrome can develop life-threatening complications, including infection and thrombosis. While AKI is associated with adverse outcomes in hospitalized children, little is known about the epidemiology of AKI in children with nephrotic syndrome. The main objectives of this study were to determine the incidence, epidemiology, and hospital outcomes associated with AKI in a modern cohort of children hospitalized with nephrotic syndrome.

Design, setting, participants, & measurements

Records of children with nephrotic syndrome admitted to 17 pediatric nephrology centers across North America from 2010 to 2012 were reviewed. AKI was classified using the pediatric RIFLE definition.

Results

AKI occurred in 58.6% of 336 children and 50.9% of 615 hospitalizations (27.3% in stage R, 17.2% in stage I, and 6.3% in stage F). After adjustment for race, sex, age at admission, and clinical diagnosis, infection (odds ratio, 2.24; 95% confidence interval, 1.37 to 3.65; P=0.001), nephrotoxic medication exposure (odds ratio, 1.35; 95% confidence interval, 1.11 to 1.64; P=0.002), days of nephrotoxic medication exposure (odds ratio, 1.10; 95% confidence interval, 1.05 to 1.15; P<0.001), and intensity of medication exposure (odds ratio, 1.34; 95% confidence interval, 1.09 to 1.65; P=0.01) remained significantly associated with AKI in children with nephrotic syndrome. Nephrotoxic medication exposure was common in this population, and each additional nephrotoxic medication received during a hospitalization was associated with 38% higher risk of AKI. AKI was associated with longer hospital stay after adjustment for race, sex, age at admission, clinical diagnosis, and infection (difference, 0.45 [log]days; 95% confidence interval, 0.36 to 0.53 [log]days; P<0.001).

Conclusions

AKI is common in children hospitalized with nephrotic syndrome and should be deemed the third major complication of nephrotic syndrome in children in addition to infection and venous thromboembolism. Risk factors for AKI include steroid-resistant nephrotic syndrome, infection, and nephrotoxic medication exposure. Children with AKI have longer hospital lengths of stay and increased need for intensive care unit admission.     

Risk Factors for Portal Vein Thrombosis in Patients With Cirrhosis Awaiting Liver Transplantation in Shiraz,Iran

Background:

Portal vein thrombosis is a fairly common and potentially life-threatening complication in patients with liver cirrhosis. The risk factors for portal vein thrombosis in these patients are still not fully understood.

Objectives:

This study aimed to investigate the associations between various risk factors in cirrhotic patients and the development of portal vein thrombosis.

Patients and Methods:

In this case-control study performed at the Shiraz organ transplantation center, Iran, we studied 219 patients (> 18 years old) with liver cirrhosis, who were awaiting liver transplants in our unit, from November 2010 to May 2011. The patients were evaluated by history, physical examination, and laboratory tests, including factor V Leiden, prothrombin gene mutation, Janus Kinase 2 (JAK2) mutation, and serum levels of protein C, protein S, antithrombin III, homocysteine, factor VIII, and anticardiolipin antibodies.

Results:

There was no statistically significant difference in the assessed hypercoagulable states between patients with or without portal vein thrombosis. A history of previous variceal bleeding with subsequent endoscopic treatment in patients with portal vein thrombosis was significantly higher than in those without it (P = 0.013, OR: 2.526, 95% CI: 1.200 - 5.317).

Conclusions:

In our population of cirrhotic patients, treatment of variceal bleeding predisposed the patients to portal vein thrombosis, but hypercoagulable disorders by themselves were not associated with portal vein thrombosis.     

Outcome of bacteremia and fungemia in paediatric oncology patients

OBJECTIVE:

To determine the outcome of paediatric oncology patients with positive blood cultures.

DESIGN:

Retrospective chart review.

SETTING:

Tertiary care hospital.

POPULATION STUDIED:

Oncology patients up to 17 years of age with positive blood cultures from January 1, 1994 to March 31, 1999.

MAIN RESULTS:

There were 121 episodes of positive blood cultures in 76 patients. Seventeen episodes were excluded because blood cultures were contaminated. Of the organisms grown from the remaining episodes, 63% were Gram-positive organisms, 23% were Gram-negative organisms, 3% were fungal and 11% were mixed. There were 13 episodes with pure or mixed isolates of Staphylococcus aureus, of which nine occurred within 14 days of the placement of a new central venous tunnelled catheter. Central venous tunnelled catheters were retained in 76 of the 102 episodes when they were present. There were two relapses, and four children were admitted to the intensive care unit with septic shock, but all survived.

CONCLUSIONS:

The outcome was excellent with the current management of possible bacteremia in paediatric oncology patients, but the high incidence of S aureus bacteremia suggests that empirical antibiotics should be altered if sepsis is suspected within 14 days of the placement of a central venous catheter.Key Words: Bacteremia, Empirical antibiotics, Fungemia, Oncology, PaediatricBacteremia and fungemia are common causes of morbidity in paediatric oncology patients. Mucositis of the gastrointestinal tract undoubtedly results in increased opportunities for bacteremia to occur. Impaired host defenses and the seeding of indwelling venous lines increase the chance that this bacteremia will be continuous rather than transient. Bacteremia also occurs following breaks in sterile technique during the manipulation of venous lines. The pathogenesis of fungemia in this patient population is not well delineated, but one likely source is from venous catheters being infected following transient fungemia from gut flora.It is standard practice to start empirical antibiotics in all febrile oncology patients who are neutropenic. The empirical antibiotic regimen used in paediatric oncology patients in our centre is tobramycin and piperacillin. Most non- neutropenic febrile oncology patients are also admitted and started on these same antibiotics, because there is evidence that their incidence of bacteremia may be at least as frequent as that of neutropenic patients (1). In our centre, venous catheters are removed in the face of suspected line infection only if the venous catheters are nontunnelled, permanent venous access is no longer required, the infecting organism is a yeast, bacteremia persists after several days of appropriate antibiotics or the patient has septic shock that is thought to be line-related. The purpose of the present study was to evaluate the outcome of patients by using this approach to suspected bacteremia or fungemia.     

Prognostic impact of pre-transplantation transfusion history and secondary iron overload in patients with myelodysplastic syndrome undergoing allogeneic stem cell transplantation: a GITMO study

Background

Transfusion-dependency affects the natural history of myelodysplastic syndromes. Secondary iron overload may concur to this effect. The relative impact of these factors on the outcome of patients with myelodysplastic syndrome receiving allogeneic stem-cell transplantation remains to be clarified.

Design and Methods

We retrospectively evaluated the prognostic effect of transfusion history and iron overload on the post-transplantation outcome of 357 patients with myelodysplastic syndrome reported to the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) registry between 1997 and 2007.

Results

Transfusion-dependency was independently associated with reduced overall survival (hazard ratio=1.48, P=0.017) and increased non-relapse mortality (hazard ratio=1.68, P=0.024). The impact of transfusion-dependency was noted only in patients receiving myeloablative conditioning (overall survival: hazard ratio=1.76, P=0.003; non-relapse mortality: hazard ratio=1.70, P=0.02). There was an inverse relationship between transfusion burden and overall survival after transplantation (P=0.022); the outcome was significantly worse in subjects receiving more than 20 red cell units. In multivariate analysis, transfusion-dependency was found to be a risk factor for acute graft-versus-host disease (P=0.04). Among transfusion-dependent patients undergoing myeloablative allogeneic stem cell transplantation, pre-transplantation serum ferritin level had a significant effect on overall survival (P=0.01) and non-relapse mortality (P=0.03). This effect was maintained after adjusting for transfusion burden and duration, suggesting that the negative effect of transfusion history on outcome might be determined at least in part by iron overload.

Conclusions

Pre-transplantation transfusion history and serum ferritin have significant prognostic value in patients with myelodysplastic syndrome undergoing myeloablative allogeneic stem cell transplantation, inducing a significant increase of non-relapse mortality. These results indicate that transfusion history should be considered in transplantation decision-making in patients with myelodysplastic syndrome.     

Risk factors for in-hospital venous thromboembolism in children: a case-control study employing diagnostic validation

Background

Studies evaluating risk factors for in-hospital venous thromboembolism in children are limited by quality assurance of case definition and/or lack of controlled comparison. The objective of this study is to determine risk factors for the development of in-hospital venous thromboembolism in children.

Design and Methods

In a case-control study at The Children’s Hospital, Colorado, from 1^st January 2003 to 31^st December 2009 we employed diagnostic validation methods to determine pediatric in-hospital venous thromboembolism risk factors. Clinical data on putative risk factors were retrospectively collected from medical records of children with International Classification of Diseases, 9th edition codes of venous thromboembolism at discharge, in whom radiological reports confirmed venous thromboembolism and no signs/symptoms of venous thromboembolism were noted on admission.

Results

We verified 78 cases of in-hospital venous thromboembolism, yielding an average incidence of 5 per 10,000 hospitalized children per year. Logistical regression analyses revealed that mechanical ventilation, systemic infection, and hospitalization duration of five days or over were statistically significant, independent risk factors for in-hospital venous thromboembolism (OR=3.29, 95%CI=1.53–7.06, P=0.002; OR=3.05, 95%CI=1.57–5.94, P=0.001; and OR=1.03, 95%CI=1.01–1.04, P=0.001, respectively). Using these factors in a risk model, post-test probability of venous thromboembolism was 3.6%.

Conclusions

These data indicate that risk of in-hospital venous thromboembolism in children with this risk factor combination may exceed that of hospitalized adults in whom prophylactic anticoagulation is indicated. Substantiation of these findings via multicenter studies could provide the basis for future risk-stratified randomized control trials of pediatric venous thromboembolism prevention.     

Nonalcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Childhood: Endocrine-Metabolic “Mal-Programming”

Context:

Nonalcoholic Fatty Liver Disease (NAFLD) is the major chronic liver disease in the pediatric population. NAFLD includes a broad spectrum of abnormalities (inflammation, fibrosis and cirrhosis), ranging from accumulation of fat (also known as steatosis) towards non-alcoholic steatohepatitis (NASH). The development of NAFLD in children is significantly increased.

Evidence Acquisition:

A literature search of electronic databases was undertaken for the major studies published from 1998 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the key words: "non-alcoholic fatty liver disease, children, non-alcoholic steatohepatitis and fatty liver".

Results:

NAFLD/NASH is probably promoted by “multiple parallel hits”: environmental and genetic factors, systemic immunological disorders (oxidative stress, persistent-low grade of inflammation) as well as obesity and metabolic alterations (insulin resistance and metabolic syndrome). However its exact cause still underdiagnosed and unknown.

Conclusions:

Pediatric NAFLD/NASH is emerging problem. Longitudinal follow-up studies, unfortunately still insufficient, are needed to better understand the natural history and outcome of NAFLD in children. This review focuses on the current knowledge regarding the epidemiology, pathogenesis, environmental, genetic and metabolic factors of disease. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for complete and personalized approach in the management of NAFLD/NASH.     

Risk of poor outcomes with novel and traditional biomarkers at clinical AKI diagnosis

Summary

Background and objectives

Studies have evaluated acute kidney injury (AKI) using biomarkers in various settings, but their prognostic utility within current practice is unclear. Thus, we sought to determine the prognostic utility of newer biomarkers or traditional markers (fractional excretion of sodium [FeNa] and urea [FeUrea] and microscopy) over clinical assessment alone.

Design, setting, participants, & measurements

This is a prospective cohort study of adults on the first day of meeting AKI criteria. We measured urine concentrations of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and IL-18 and determined FeNa, FeUrea, and microscopy score for casts and tubular cells. Primary outcome was worsened AKI stage from enrollment to peak serum creatinine or in-hospital death.

Results

In 249 recipients, 57% were ≥65 years old, 48% were from intensive care, and mean baseline GFR was 69 ± 30 ml/min per 1.73 m². AKI was considered prerenal in 164 (66%), acute tubular necrosis (ATN) in 51 (20%), and “other” in 34 (14%). All mean protein biomarker concentrations, FeNa, FeUrea, and microscopy scores were statistically different between prerenal and ATN. Seventy-two patients (29%) developed the primary outcome. There was an approximate three-fold increase in adjusted risk for the outcome for upper versus lower values of NGAL, KIM-1, IL-18, and microscopy score (P values <0.05). Net reclassification improved after adding these to baseline clinical assessment. FeNa and FeUrea were not useful.

Conclusions

On the first day of AKI, urine protein biomarkers and microscopy significantly improve upon clinical determination of prognosis, indicating their potential utility in current practice.