High-risk Clinical Features Research Articles

The use of analgesics in patients with asthma.

Aspirin (acetylsalicylic acid) and other nonsteroidal anti-inflammatory drugs (NSAIDs) cause deterioration in respiratory function in approximately 10% of adults with asthma and a smaller proportion of children with asthma. We propose evidence-based guidelines for the safe use of NSAIDs in individuals with asthma following systematic review of data from the last 10 years relevant to the use of these drugs in such patients. We would currently recommend that patients with asthma who are known to be intolerant of NSAIDs or who exhibit any of the high risk clinical features for intolerance to these drugs (severe asthma, nasal polyps or chronic rhinosinusitis) should use NSAIDs only under close medical supervision. In those with high risk features formal aspirin provocation testing would be recommended prior to the therapeutic use of NSAIDs. Those individuals with asthma who regularly use NSAIDs can continue to do so but should be warned that intolerance to NSAIDs can develop late in life. Lack of relevant experimental evidence precludes the production of evidence-based guidelines for the group of patients with asthma who do not exhibit high risk clinical features and who have never before used NSAIDs. We would currently recommend that this group be treated as potentially intolerant to NSAIDs and use of these drugs can only be recommended under medical supervision but note that further studies and clinical experience could be expected to relax this restriction for many patients. Recent data have suggested that frequent use of paracetamol (acetaminophen) may contribute to a deterioration of respiratory function in asthma. A small proportion of patients with asthma who are NSAID-intolerant experience short-lived deterioration in respiratory function with the use of high doses of paracetamol but this is uncommon and has not been implicated in life-threatening reactions. Routine warnings about paracetamol use in asthma are, therefore, not warranted. Medical personnel, however, should be aware of the potential for worsening of symptoms in some individuals with asthma using paracetamol and institute formal investigation or withdrawal of the drug if they suspect such a reaction.

Role of transthoracic echocardiography in atrial fibrillation.

Atrial fibrillation is a major clinical problem that is predicted to be encountered more frequently as the population ages. The clinical management of atrial fibrillation has become increasingly complex as new therapies and strategies have become available for ventricular rate control, conversion to sinus rhythm, maintenance of sinus rhythm, and prevention of thromboembolism. Clinical and transthoracic echocardiographic features are important in determining etiology and directing therapy for atrial fibrillation. Left atrial size, left ventricular wall thickness, and left ventricular function have independent predictive value for determining the risk of developing atrial fibrillation. Left atrial size may have predictive value in determining the success of cardioversion and maintaining sinus rhythm in selected clinical settings but has less value in the most frequently encountered group, patients with nonvalvular atrial fibrillation, in whom the duration of atrial fibrillation is the most important feature. When selecting pharmacological agents to control ventricular rate, convert to sinus rhythm, and maintain normal sinus rhythm, transthoracic echocardiography (TTE) allows noninvasive evaluation of left ventricular function and hence guides management. The combination of clinical and transthoracic echocardiographic features also allows risk stratification for thromboembolism and hemorrhagic complications in atrial fibrillation. High-risk clinical features for thromboembolism supported by epidemiological observations, results of randomized clinical trials, and meta-analyses include rheumatic valvular heart disease, prior thromboembolism, congestive heart failure, hypertension, older (> 75 years old) women, and diabetes. Small series of cases also suggest those with hyperthyroidism and hypertrophic cardiomyopathy are at high risk. TTE plays a unique role in confirming or discovering high-risk features such as rheumatic valvular disease, hypertrophic cardiomyopathy, and decreased left ventricular function. Validation of the risk stratification scheme used in the Stroke Prevention in Atrial Fibrillation-III trial is welcomed by clinicians who are faced daily with balancing the benefit and risks of anticoagulation to prevent thromboembolism in patients with atrial fibrillation.

Comparison of cardiac troponin T versus creatine kinase-mb for risk stratification in a chest pain evaluation unit

We evaluated cardiac troponin T (cTnT) and creatine kinase-MB (CK-MB) for risk stratification of chest pain unit (CPU) patients. We studied 383 consecutive patients with chest pain assigned to our CPU by emergency department physicians. At baseline all had normal or nondiagnostic electrocardiograms, no high-risk clinical features, and negative CK/CK-MB. CK-MB and electrocardiograms were taken at 0, 4, 8, and 12 hours and cTnT at 0, 4, and 8 hours. Eight patients (2.1%) were CK-MB positive and 39 (10.2%) were cTnT positive, including all but 1 CK-MB-positive patient. All marker-positive patients were detected by 8 hours. Seven cTnT-positive patients and 1 cTnT-negative patient had myocardial infarction (p <0.0001). cTnT-positive patients were older, less likely to be women or smokers, and more often had diabetes mellitus or known coronary disease (CAD). Seventy-one percent of patients underwent diagnostic testing. cTnT-positive patients more often underwent angiography (46% vs 20%) and underwent stress testing less often (28% vs 57%) than cTnT-negative patients. When performed, their stress tests were more often positive (46% vs 14%) and they more often had angiographically significant lesions (89% vs 49%) and multivessel disease (67% vs 29%). There were no short-term deaths. Long-term mortality was higher in cTnT-positive patients (27% vs 7%, p <0.0001). Thus, cTnT identified more CPU patients with myocardial necrosis and multivessel CAD than CK-MB and a population with high long-term mortality risk. Routine use of cTnT in CPUs could facilitate risk stratification and management.

Utility of cardiac troponin I, creatine kinase-MBmass, myosin light chain 1, and myoglobin in the early in-hospital triage of “high risk” patients with chest pain

OBJECTIVETo evaluate the use of cardiac troponin I (cTnI), creatine kinase-MBmass (CK-MBmass), myosin light chain 1 (MLC 1), and myoglobin in identifying “high risk” patients with chest pain who will...

Laser treatment in subjects with high-risk clinical features of age-related macular degeneration. Posterior pole appearance and retinal function.

To verify that a few laser lesions in the posterior pole can cause drusen to resolve in patients with age-related macular degeneration, and to document central retinal sensitivity as drusen resolve. In a pilot study, 12 patients considered to be at high risk for sight-threatening complications from age-related macular degeneration were treated with 12 argon laser lesions in the posterior pole, with review for 12 to 24 months. Choroidal neovascularization developed in 1 patient 8 months after treatment, with consequent loss of central vision. In 9 of the remaining 11 patients, high-risk characteristics of drusen were reduced. Four patients had retinal pigment epithelial depigmentation, and all maintained 20/40 visual acuity at 12 months. One patient lost 3 lines of vision due to geographic atrophy after 12 months. Scotopic retinal threshold was elevated before treatment in 8 patients, compared with an age-matched comparison group. Of these, 4 patients underwent retesting 3 to 6 months after treatment, and all had improved thresholds, but only 1 patient sustained the improvement at 12 months. At 12 months, 3 of the 8 patients showed an improvement in their mean retinal threshold. Of those in whom the mean retinal threshold worsened, the mean elevation in threshold was not more than 0.6 log units. A few laser lesions in the posterior pole leads to resolution of drusen. There does not appear to be an increased risk for choroidal neovascularization. Retinal threshold measurements show no indication of geographic atrophy at 1 year, but cannot be excluded as a late outcome. Laser treatment may reduce the risk for profound sight-threatening lesions in age-related macular degeneration.

Impact of chromosomal translocations on prognosis in childhood acute lymphoblastic leukemia.

The presence of a chromosomal translocation in the leukemic cells at diagnosis of acute lymphoblastic leukemia (ALL) in children is associated with a high risk for treatment failure. We have reexamined the relationship between translocations and prognosis in 146 children with ALL who received risk-based therapy such that high-risk patients were treated with intensive drug schedules. In univariate analysis, multiple factors were associated with a relatively poor event-free survival (EFS) including age less than 2 years or greater than 10 years (combined group), WBC count greater than 10 x 10(9)/L, French-American-British (FAB) morphologic classification L2, absence of common ALL antigen (CALLA, CD10) expression, absence of hyperdiploidy with a chromosome number of 50 to 60, and presence of the specific translocations t(4; 11)(q21;q23) or t(9;22)(q34;q11) (combined group). However, there was no disadvantage with respect to EFS in patients with translocations compared with those who lacked translocations (73% at 4 years in both groups). Furthermore, when patients with specific cytogenetic abnormalities for which the prognostic significance has been well established (hyperdiploid 50 to 60, t(4;11), and t(9;22] were removed from the analysis, the remaining group with other translocations had a better EFS than the remaining group lacking translocations, although this was not statistically significant (81% v 65% at 4 years, P = .24). In a multivariate analysis, a model including WBC count and FAB classification was the strongest predictor of EFS. The presence or absence of translocations was not an independent predictor of EFS and did not contribute to the ability of any model to predict EFS. In conclusion, when effective intensive therapy is used to treat childhood ALL with high-risk clinical features, categorization of patients on the basis of chromosomal translocations without attention to the specific abnormality is not useful as a prognostic factor.

Nonrandom Abnormalities of Chromosome 9p in Childhood Acute Lymphoblastic Leukemia: Association With High-Risk Clinical Features

AbstractTo assess the frequency and significance of nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia (ALL), we analyzed our experience with 398 consecutive cases with completely banded karyotypes. Forty cases (10%) with abnormalities of 9p were identified: 26 with deletions, nine with unbalanced translocations resulting in the loss of 9p material, and five with apparently balanced reciprocal translocations. As compared with children with ALL lacking 9p abnormalities, these 40 cases were significantly older, had higher initial circulating WBC counts, more “lymphomatous” disease characteristics (including presence of a mediastinal mass in 15%, T-cell phenotype in 26%, splenomegaly >8 cm in 25%), an increased failure rate in the first 2 to 3 years after diagnosis, and a higher incidence of extramedullary relapse. Conversely, lymphomatous ALL cases were twice as likely (19% v 8%) to have an abnormality of chromosome 9p than ALL cases lacking lymphomatous features (P =.01). The finding of an abnormal chromosome 9p, however, was not specific for lymphomatous ALL or T-cell lineage, because most cases were neither lymphomatous nor T-cell, and the overall Kaplan-Meier distribution of treatment failures for abnormal 9p cases was not statistically significantly different from control ALL cases receiving the same treatment who lacked abnormalities of 9p (P =.06, by log-rank test). We conclude that nonrandom abnormalities of chromosome 9p, especially a breakpoint in 9p21 -22, occur with increased frequency in childhood ALL in association with some high-risk clinical features. Despite this association, the chromosome anomaly is nonspecific in its syndrome delineation and confers no major adverse consequence on long-term survival of childhood ALL treated with modern therapy. However, due to an apparently increased hazard of involvement of the CNS (eight of 17 failures), it may be inadvisable to lessen the intensity of CNS preventive therapy for this group of patients.

Nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia: association with high-risk clinical features

To assess the frequency and significance of nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia (ALL), we analyzed our experience with 398 consecutive cases with completely banded karyotypes. Forty cases (10%) with abnormalities of 9p were identified: 26 with deletions, nine with unbalanced translocations resulting in the loss of 9p material, and five with apparently balanced reciprocal translocations. As compared with children with ALL lacking 9p abnormalities, these 40 cases were significantly older, had higher initial circulating WBC counts, more "lymphomatous" disease characteristics (including presence of a mediastinal mass in 15%. T-cell phenotype in 26%, splenomegaly greater than 8 cm in 25%), an increased failure rate in the first 2 to 3 years after diagnosis, and a higher incidence of extramedullary relapse. Conversely, lymphomatous ALL cases were twice as likely (19% v 8%) to have an abnormality of chromosome 9p than ALL cases lacking lymphomatous features (P = .01). The finding of an abnormal chromosome 9p, however, was not specific for lymphomatous ALL or T-cell lineage, because most cases were neither lymphomatous nor T-cell, and the overall Kaplan-Meier distribution of treatment failures for abnormal 9p cases was not statistically significantly different from control ALL cases receiving the same treatment who lacked abnormalities of 9p (P = .06, by log-rank test). We conclude that nonrandom abnormalities of chromosome 9p, especially a breakpoint in 9p21-22, occur with increased frequency in childhood ALL in association with some high-risk clinical features. Despite this association, the chromosome anomaly is nonspecific in its syndrome delineation and confers no major adverse consequence on long-term survival of childhood ALL treated with modern therapy. However, due to an apparently increased hazard of involvement of the CNS (eight of 17 failures), it may be inadvisable to lessen the intensity of CNS preventive therapy for this group of patients.