Specific Clinical Risk Factors Research Articles

Stent Thrombosis Associated with First-generation Drug-eluting Stents – Issues with Antiplatelet Therapy

The rare but catastrophic occurrence of stent thrombosis, in particular 'late' stent thrombosis, in association with deployment of drug-eluting stents has focused attention on the adequacy of the current dual anti-platelet regimen of aspirin and clopidogrel. Stent thrombosis is due to multiple factors. These include, specific stent features (delayed healing or polymer hypersensitivity), procedural factors (stent length and stent malapposition) and clinical risk factors such as lack of response to, or premature discontinuation of, anti-platelet treatment.

Clinical Challenges and Unmet Needs in the Management of Complicated Intra-abdominal Infections

Management of complicated intra-abdominal infections involves invasive procedures for control of the source of the infection and antimicrobial therapy directed against gram-negative and anaerobic pathogens. Application of these management principles to the individual patient is essential to optimize the patient's chances for recovery, while also avoiding unnecessary therapy that may have no clinical benefits, or that may carry risk. Based on a review of the literature, treatment guidelines, and expert opinion, the challenges of managing patients with complicated intra-abdominal infections are summarized using a patient stratification approach: "Lower risk" of treatment failure and death vs. "higher risk." Risk factors for treatment failure and death can be grouped into several categories, including the patient's pre-existing medical comorbidities and physiological response to the infection, the extent of the intra-abdominal infection, and the presence of specific pathogenic microorganisms. These latter factors may be more useful than the Acute Physiology and Chronic Health Evaluation (APACHE) II score in evaluating specific management strategies for patients with complicated intra-abdominal infections. The principal goal of treatment in lower-risk patients is to avoid morbidity related to source control procedures and antimicrobial therapy. Limitation of the scope of source control procedures and utilization of short-duration, narrow-spectrum, low-toxicity antimicrobial regimens is advisable to avoid adverse drug reactions and selection of resistant organisms. For higher-risk patients, the goal is to develop improved management modalities, so that morbidity and mortality are reduced. The recommended approach for higher-risk patients is to identify the most appropriate source control procedure and antimicrobial therapy, as dictated by the patient's specific risk factors, and to utilize the optimal tools of critical care medicine to treat these critically ill, septic patients. The emergence of bacterial resistance also must be considered when selecting antimicrobial therapy for both low risk and high risk patients with intra-abdominal infections. Because aminoglycoside regimens are becoming less favored, and optimal therapeutic strategies have not been standardized, the use of new treatment options (e.g., tigecycline) may be valuable when managing patients with intra-abdominal infections, especially for resistant isolates. The management of lower-risk patients with intra-abdominal infections is distinct compared with patients at higher risk due to compromised physiological status, extent of intra-abdominal infection, or presence of nosocomial pathogens associated with higher-risk patients. Carefully designed, multidisciplinary-sponsored, clinical trials in patients with specific clinical risk factors are needed to better assess the role of various antimicrobial regimens in the treatment of higher-risk patients with intra-abdominal infections.

Risk factors for pediatric human immunodeficiency virus-related malignancy.

Although cancers occur with increased frequency in children with human immunodeficiency virus (HIV) infection, the specific clinical, immunological, and viral risk factors for malignancy have not been identified. To identify risk factors for malignancy among HIV-infected children. A multicenter case-control study of children with HIV at 26 institutions participating in the Pediatric Oncology Group. Forty-three case patients with a new malignancy and 74 control patients without a malignancy were matched based on the duration of their infection. Patients were enrolled between January 1992 and July 1998. Clinical and laboratory factors assessed as putative risk factors included demographic characteristics, HIV characteristics, prior antiretroviral treatment, and CD4 cell count. Coviral infections with Epstein-Barr virus (EBV), cytomegalovirus, and human herpesvirus 6 were assessed by semiquantitative polymerase chain reaction assays and serological testing. Case malignancy diagnoses included 28 non-Hodgkin lymphoma, 4 B-cell acute lymphoblastic leukemia, 1 Hodgkin disease, 8 leiomyosarcoma, 1 hepatoblastoma, and 1 schwannoma. Epstein-Barr virus viral load of more than 50 viral genome copies per 105 peripheral blood mononuclear cells was strongly associated with cancer risk but only for children with CD4 cell counts of at least 200/ microL (odds ratio [OR], 11.33; 95% confidence interval [CI], 2.09-65.66, P<.001). High EBV viral load was not associated with cancer for children with CD4 cell counts of less than 200/ microL (OR, 1.12; 95% CI, 0.13-9.62; P =.99). Zidovudine antiretroviral therapy did not confer a significant protective effect for either the high (OR, 0.81; 95% CI, 0.22-3.09; P =.77) or the low CD4 cell count groups (OR, 0.27; 95% CI, 0.04-1.46; P =.16). The route of HIV infection was not associated with increased cancer risk. Route of infection, demographic characteristics, and zidovudine use were not associated with the development of malignancy in HIV-infected children. High viral burden with EBV was associated with the development of malignancy in HIV-infected children although the effect was modified by CD4 cell count. The pathogenesis of HIV-related pediatric malignancies remains unclear and other contributing risk factors can be elucidated only through further study.

Contribution of clinical risk factors to bone density-based absolute fracture risk assessment in postmenopausal women.

Hip fractures are independently associated with advancing age, specific clinical risk factors (CRFs), and low bone mineral density (BMD). The use of BMD T-scores for quantifying fracture risk ignores the contribution of age and CRFs. We previously developed a mathematical model of absolute hip fracture risk that incorporates patient age, BMD, and the results of eleven specific CRFs. The purpose of this study was to compare the contribution of an approach to fracture risk stratification using the full model (age, CRFs and BMD) with that of a unidimensional BMD-only model. We selected 213 consecutive postmenopausal females (mean age 65.3, range 50-87.9) with CRF data referred for BMD assessment of fracture risk. Absolute hip fracture risk (over the next 5 years and remaining lifetime) was estimated using both the full and BMD-only models. The mean ratio of absolute hip fracture risks (BMD-only/full model) derived for each patient was 0.8 (95% CI, 0.16-4.0) for hip fracture in the next 5 years and 1.1 (CI, 0.1-7.6) for remaining lifetime. The wide confidence intervals indicate a large contribution of age and CRFs to fracture risk stratification. Categorization of women as "high risk" was frequently discordant for the two models. One-half of the women designated "high risk" under the full model were classified as "low risk" based upon BMD alone. In conclusion, we have shown that a multidimensional approach to hip fracture risk stratification is feasible, and greatly modifies risk stratification based on BMD alone.

Risk assessment of venous thromboembolism in medical patients

Medical patients are at risk of venous thromboembolism (VTE). However, the extent of the risk is not well characterized. Risk stratification is an important part of effective thromboprophylactic management. The risks depend on the specific clinical risk factors in individual patients and include age, immobility, and prior history of VTE. Medical patient risk assessment models (RAMs) are not fully developed, but a number of specific risk factors have been characterized. Although at present prophylactic treatment is largely empirical, studies evaluating the effects of higher-dose regimens in at-risk patients are ongoing. Long-term prophylaxis may be of benefit to particular patient populations, including those with congenital and acquired aberrations in hemostasis. Published studies of low-molecular-weight heparins (LMWHs) show that these agents are at least as effective as low-dose unfractionated heparin (UFH), with a trend towards an improved safety profile. The results of ongoing studies will provide further insight into the risk of VTE in this important patient group.

A pedigree of Leber's hereditary optic neuropathy with visual loss in childhood, primarily in girls.

Leber's hereditary optic neuropathy (LHON) mostly affects young males. In patients carrying one of the primary mutations the risk to develop LHON is 50% for males and 10% for females. We report a family with predominantly young girls affected. In a family with 14 known maternal relatives (11 females, 3 males) 9 patients in 4 generations developed LHON. Eight of the 9 patients were females. Three affected females could be examined and followed. The only affected male showed the typical course of LHON with acute visual loss in both eyes (20/400-20/800) within 6 weeks at 20 years of age. Eight of 9 females developed signs of LHON. In these females acute visual loss occurred at about 10 years of age. Final visual acuity was about 20/200. Central or paracentral scotomata, color vision defects and delayed P100 latencies in the VEP were seen. Ophthalmoscopy showed hyperemic discs in the acute stage and optic atrophy in later stages. Molecular genetic analysis revealed the presence of the mtDNA ND4/np11778 mutation in this family. Specific clinical or additional molecular genetic risk factors could not be detected. Families with LHON may show considerable variations of the clinical course and the gender- or age-specific risk. We present a family with a high disease penetrance of 64% and a 2 times higher risk for young females than for males. Furthermore, early visual loss in this family is permanent.

Constitutional WT1 mutations in Wilms' tumor patients.

Patients with Wilms' tumors (WT) who carry constitutional mutations in the WT1 gene have been described in case reports and small case series. We sought to determine the frequency of constitutional WT1 mutations in a larger cohort, and to identify clinical manifestations associated with the risk for carrying a WT1 mutation. We collected clinical data and blood samples from 201 patients with a history of WT. Southern blot analysis, single-strand conformation polymorphism (SSCP) analysis, and direct DNA sequencing were performed on DNA isolated from peripheral-blood lymphocytes from each patient. Odds ratios (ORs) for the carriage of a germline mutation of the WT1 gene were calculated for patients who had specific clinical risk factors compared with those who did not. Of 201 patients with WT in the cohort, eight patients were carriers of mutations in the WT1 gene. Six of the eight mutations were protein-truncating nonsense mutations. None of 56 patients with isolated unilateral WT was a carrier. The OR of carrying a WT1 mutation was elevated for patients with genitourinary anomalies (OR19.3; P < .002). Seven of 28 boys with WT with cryptorchidism carried WT1 mutations. No increased risk was observed for patients with nephrogenic rests, bilateral tumors, history of secondary cancers, or family history of WT. Germline WT1 mutations in patients with WT are associated with genitourinary anomalies, especially cryptorchidism and/or hypospadias. Patients with WT and no genitourinary anomalies are at low risk for carrying a WT1 mutation. Constitutional WT1 mutations that encode truncated WT1 proteins may predispose to the development of cryptorchidism, hypospadias, and WTs.

Increasing the clinical yield of computerized tomography for psychiatric patients

Computerized tomography (CT) continues to be extensively utilized to exclude intracranial pathology in psychiatric practice, but little is known about clinical risk factors, which might predict those patients most likely to benefit from the procedure. We reviewed 150 cases of psychiatric patients who received CT scans to exclude intracranial pathology. We assessed the relationships of patient age, psychiatric diagnosis, and findings from neurologic and cognitive examinations to CT results that influenced patient care, and overall normal and abnormal CT results. Fifty-three percent of the CT scans were abnormal, 11% influenced patient care, and only 2% identified potentially reversible lesions. Cognitive exam results and, to a lesser extent, neurologic exam results, were sensitive predictors of CT findings that influenced patient care. All patients with clinically influential CT results had cognitive deficits and all but one had neurologic deficits. Patients older than 60 years of age and those with organic mental syndromes were most likely to have clinically influential CT findings. Our results suggest that utilizing specific clinical risk factors such as findings from clinical examinations, patient age, and psychiatric diagnosis, to guide the ordering of CT scans, can greatly increase the yield of the procedure for psychiatric patients, without excess medical morbidity.

Relation of thrombus in the left atrial appendage by transesophageal echocardiography to clinical risk factors for thrombus formation

Transesophageal echocardiography provides excellent visualization of the left atrial appendage (LAA). This study was conducted to determine whether specific clinical risk factors could predict the presence of LAA thrombus as demonstrated by transesophageal echocardiography. The most recent 860 transesophageal echocardiographic studies performed at our institution were retrospectively reviewed. The LAA was adequately visualized in 778 patients (90%). For each study, the presence or absence of 5 specific clinical risk factors (mitral stenosis, severe left ventricular dysfunction, left atrial dilatation, atrial fibrillation, or a prosthetic mitral valve) and the presence or absence of LAA thrombi were assessed. One or more clinical risk factors were present in 149 patients, whereas no defined risk factors were noted in 629. Left atrial appendage thrombi were found in 20 of 149 patients with versus 6 of 629 patients without a clinical risk factor (13% vs 1%, p = 0.0001). By logistic regression analysis, mitral stenosis, severe left ventricular dysfunction, and left atrial dilatation were independent risk factors for LAA thrombus formation. Neither atrial fibrillation nor the presence of a mitral prosthetic valve achieved statistical significance as independent risk factors for LAA thrombus. Thus, LAA thrombi occur most often in patients with risk factors for thrombus formation that can be determined by clinical evaluation and transthoracic echocardiography. Transesophageal echocardiography rarely identifies LAA thrombi in patients without such clinical risk factors.

A Critique of the Use of Generic Screening in Quality Assessment

This article summarizes available information on the efficiency and effectiveness of generic occurrence screening when used in quality assessment. Generic screening is relatively inefficient because of its multitiered review system and high rates of errors and false positives. Overall sensitivity may approach 70% to 80%, but specificity is estimated to range from about 22% to 73%. Effectiveness of generic screening in identifying problems in quality is limited by variability in peer review. Other limitations of generic screens include their lack of inherent relationship to the quality of patient care and their inability to provide direct performance measures for use in the periodic reappraisal of clinical privileges of medical staff members. We propose the monitoring of specific adverse surgical and medical clinical outcomes and related risk factors to increase efficiency in quality assessment and provide a more adequate database for the continual improvement of patient care and clinical performance.

Screening for occupational disease among workers in a high‐risk trade: Examination of cost, yield, and potential for increased efficiency

We evaluated the cost and yield of a general health surveillance program emphasizing the identification of occupationally related diseases among workers in a high-risk trade. Of approximately 4,000 eligible members of two local plumbers and pipefitters unions, 639 were screened in this program. Screening tests indicated either by specific occupational exposures (eg, chest X-ray, spirometry, and audiometry) or general clinical risk factors (urine analysis for those with a positive urine dipstick, and stool heme occult testing for those over 45 years of age) proved to be far less costly for each positive finding than those procedures (physical examination, complete blood count, and blood chemistry panel) that were not specifically indicated. A discriminant analysis revealed predictor variables (age, years in the trade, and presence of respiratory symptoms) that, in subsequent screening efforts, could be used in the unscreened population either to identify individuals who are more likely to have any positive test result or to "tailor" the content of the initial screening program for a single individual. Increasing the yield and decreasing the direct costs of screening activities may make programs like these more affordable. In addition, this program assisted workers in filing for compensation and thus served to promote the appropriate transfer of cost for the identification and management of occupational diseases from traditional forms of payment to workers' compensation insurance programs.