Leonardo Tamariz

The evolution of Lemierre syndrome: Report of 2 cases and review of the literature

Lemierre syndrome (postanginal septicemia) is caused by an acute oropharyngeal infection with secondary septic thrombophlebitis of the internal jugular vein and frequent metastatic infections. A high degree of clinical suspicion is necessary for diagnosis. Fusobacterium necrophorum is the usual etiologic agent. The disease progresses in several steps. The first stage is the primary infection, which is usually a pharyngitis (87.1% of cases). This is followed by local invasion of the lateral pharyngeal space and IJV septic thrombophlebitis (documented in 71.5% of cases), and finally, the occurrence of metastatic complications (present in 90% of cases at the time of diagnosis). A sore throat is the most common symptom during the primary infection (82.5% of cases). During invasion of the lateral pharyngeal space and IJV septic thrombophlebitis, a swollen and/or tender neck is the most common finding (52.2% of patients) and should be considered a red flag in patients with current or recent pharyngitis. The most common site of metastatic infection is the lungs (79.8% of cases). In contrast to the preantibiotic era, cavitating pneumonia and septic arthritis are now uncommon. Most patients (82.5%) had fever at some stage during the course of the disease. Gastrointestinal complaints such as abdominal pain, nausea, and vomiting were common (49.5% of cases). An elevated white blood cell count occurred in 75.2% of cases. Hyperbilirubinemia with slight elevation of liver enzyme levels occurred in one-third of patients, but frank jaundice was uncommon, in contrast to its high frequency reported in the preantibiotic era. We conclude that, most likely as a consequence of widespread antibiotic use for pharyngeal infections, the typical course of the disease has changed since Lemierre’s original description. The typical triad in our series was: pharyngitis, a tender/swollen neck, and noncavitating pulmonary infiltrates. The previous classical description of severe sepsis with cavitating pneumonia and septic arthritis was not commonly seen in our review. Mortality was low in our series (6.4%), but significant morbidity occurred, which was likely preventable by early diagnosis and treatment. The pathophysiology, natural history, diagnostic methods for internal jugular vein thrombosis, and management are discussed.

Management of Atrial Fibrillation: Review of the Evidence for the Role of Pharmacologic Therapy, Electrical Cardioversion, and Echocardiography

Atrial fibrillation is the most common type of arrhythmia in adults, accounting for about one third of hospitalizations for arrhythmia (1). The prevalence increases from less than 1% in persons younger than 60 years of age to more than 8% in those older than 80 years of age (2-6). The incidence ranges from 0.2% per year for men 30 to 39 years of age to 2.3% per year in men 80 to 89 years of age (7, 8). The age-adjusted incidence for women is about half that of men (9). The cardiac conditions most commonly associated with atrial fibrillation are rheumatic mitral valve disease, coronary artery disease, congestive heart failure, and hypertension (8, 10). Noncardiac causes include hyperthyroidism, hypoxic conditions, surgery, and alcohol intoxication. A predisposing condition exists in more than 90% of cases (5, 11, 12); the remaining cases have what is called lone atrial fibrillation. Patients with atrial fibrillation frequently have symptoms of hemodynamic compromise, ranging from irregular palpitations to the more insidious feeling of malaise. They also have an increased risk for thromboembolism. Comparing with age-matched controls, the relative risk for stroke is increased 2- to 7-fold in patients with nonrheumatic atrial fibrillation (3, 8, 13), and the absolute risk for stroke is between 1% and 5% per year, depending on clinical characteristics (3, 12, 14-16). Quality of life is an important consideration for patients. Paroxysmal atrial fibrillation disrupts the lives of patients (17), but this perception may not be associated with frequency or duration of symptoms. Warfarin therapy affects quality of life because of frequent blood testing and recommendations for limiting some activities. Gage and colleagues (18) found that atrial fibrillation decreases utility, a quantitative assessment of quality of life used in decision analysis, by 1.3%. Protheroe and associates (19) found that only 61% of patients would prefer anticoagulation to no treatment, considerably fewer than those for whom guidelines would recommend treatment. Little is known about the direct effects of antiarrhythmic therapy and rate-control therapy on quality of life. The American College of Cardiology/American Heart Association/European Society of Cardiology Task Force on Clinical Guidelines for the Management of Atrial Fibrillation classified atrial fibrillation into 4 types (20): first detected episode, paroxysmal (terminates spontaneously), persistent (electrical or pharmacologic termination necessary), and permanent (resistant to electrical or pharmacologic conversion or accepted by the physician). The purpose of this review was to summarize the evidence that was available during formulation of the guidelines developed by the American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) for management of adult patients with nonpostoperative atrial fibrillation. The foundation of this background paper was a systematic review of the pharmacologic management of atrial fibrillation that examined the efficacy of medications used for stroke prevention, ventricular rate control, acute conversion, and maintenance of sinus rhythm, as well as the role of echocardiography in guiding pharmacologic therapy (21). For this updated version of the systematic review, we considered observational data, consensus statements, decision analyses, and relevant guidelines. This review focused on the evaluation and pharmacologic management of adult patients with nonpostoperative atrial fibrillation. The rapidly advancing field of nonpharmacologic management of atrial fibrillation is outside the scope of this paper. Methods A full description of the methods used in the systematic review can be found in a detailed evidence report (21). A brief description of these methods and additional methods specific to this article are given below. Literature Identification Whenever possible, we focused our searches for relevant evidence on the strongest study design: randomized, controlled trials (RCTs). For our previous systematic review, we identified controlled trials in the CENTRAL database produced by the Cochrane Collaborations international efforts, searched MEDLINE from 1966 to 1998 for citations tagged as randomized, controlled trial or controlled clinical trial, searched the PubMed Related Articles feature, reviewed hand searches submitted to the Baltimore Cochrane Center, scanned the reference lists in relevant publications, and scanned the table of contents of relevant journals. For the current review, we also searched MEDLINE from May 1998 through September 2001 (using the same search terms as in the original review plus terms to identify meta-analyses and decision analyses). For topics without sufficient RCTs, we used observational data, consensus statements, review articles, and decision analyses obtained from our search of MEDLINE from 1966 through September 2001. Although we had to use September 2001 as a cutoff for the systematic searching of the literature in order to generate a report for the ACPAAFP Guideline group, we included selected studies published after September 2001 on the basis of input from the group. Article Review Process Studies were eligible for review if they were randomized trials of adult patients that addressed the management of nonpostoperative atrial fibrillation. In the previous systematic review, 521 citations were identified and 179 articles were eligible for detailed review. The updated search yielded 29 additional articles that met our inclusion criteria. Statistical Analysis For the quantitative analysis, we stratified the data to obtain an effect measure for each drug. We used Stata, version 7.0 (Stata Corp., College Station, Texas) to calculate the odds ratio (OR) of success of the drug compared with placebo. Respective 95% CIs and P values were also calculated. We used ORs because they provide less heterogeneity of study results than relative risk ratio. Estimates of the relative rates of the outcomes of interest were pooled by using standard methods for combining the OR for the outcomes of conversion to sinus rhythm, maintenance of sinus rhythm, stroke, peripheral embolism, major bleeding, minor bleeding, and death (21). Studies were weighted on the basis of the precision of the estimate within each study. When no heterogeneity was found, meta-analyses used the fixed-effects model (MantelHaenszel method for pooling) (22). When heterogeneity was found, the random-effects model was used (DerSimonian and Laird method of pooling) (23). An OR was considered significantly different from 1 if the P value was less than 0.05. Statistical strength of evidence was categorized as strong (P 0.01), moderate (0.01 < P 0.05), suggestive (0.05 < P 0.2), or inconclusive (P > 0.2). Role of the Funding Sources The initial systematic review was funded through a contract with the Agency for Healthcare Research and Quality (21). Subsequent work was supported by the American College of Physicians. Drafts of the manuscript were reviewed by members of the ACP/AAFP guidelines committee for management of atrial fibrillation. Data Synthesis Does Aggressive Rhythm Control Improve Mortality and Morbidity Compared with Rate Control? Although the relative benefits and risks of rate versus rhythm control are of paramount importance in the management of atrial fibrillation, studies directly addressed this issue only recently. By far the largest, the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial was a multicenter RCT that enrolled 4060 patients from more than 200 sites in Canada and the United States (24). Eligibility criteria included documented atrial fibrillation lasting at least 6 hours and at least 1 risk factor for stroke (age >65 years, hypertension, diabetes mellitus, previous stroke, and poor ventricular function). Average age was 70 years. Sixty-one percent of patients were men, 89% were white, 71% had hypertension, 38% had coronary artery disease, and 18% had had failure of antiarrhythmic therapy. After patients were randomly assigned to the rhythm-control or rate-control group, physicians could choose from a list of pharmacologic and nonpharmacologic therapies. Although anticoagulation was continued indefinitely for the rate-control group, discontinuation of anticoagulation was permitted at 1 month or later following conversion in the rhythm-control arm. The mortality rate at 5 years was 23.8% in the rhythm-control group and 21.3% in the rate-control group (hazard ratio, 1.15 [95% CI, 0.99 to 1.34]; P = 0.08). Combined central nervous system ischemic strokes and hemorrhagic events occurred in 8.9% of patients in the rhythm-control group and 7.4% of patients in the rate-control group (P > 0.2). Eighty-five patients in the rhythm-control group and 79 in the rate-control group had strokes (P > 0.2). Of note, more than 70% of the strokes in both groups occurred in patients who had stopped taking anticoagulant therapy or who had an international normalized ratio less than 2.0. Preliminary analyses of other secondary end points, including quality of life and functional capacity, did not show statistical difference between treatment groups. However, more hospitalizations occurred in the rhythm-control group. A smaller study conducted in the Netherlands, the RAte Control versus Electrical cardioversion for persistent atrial fibrillation (RACE) study (25), randomly assigned 522 patients to aggressive rhythm control or rate control only. Mean age was 68 years. Sixty-four percent were men, 49% had hypertension, and 27% had coronary artery disease. The primary composite end point of cardiovascular mortality, heart failure, thromboembolic complications, bleeding, pacemaker implantation, and severe side effects of antiarrhythmic drugs occurred in 17.2% of patients in the rate-control group and in 22.6% of patients in the rhythm-control group over a mean of 2.3 years. Thus, rate control was not inferior

Inflammatory Bowel Disease Is Associated With an Increased Incidence of Cardiovascular Events

OBJECTIVES:Patients with inflammatory bowel disease (IBD) present with several extraintestinal manifestations, including systemic inflammation and hypercoagulability. Limited studies have shown that patients with IBD may have a higher risk of developing atherosclerosis. The incidence of coronary artery disease (CAD) and the role of traditional CAD risk factors in IBD patients remain unclear. We sought to compare the rates of CAD events in patients with IBD with matched controls.METHODS:We performed a longitudinal cohort study of patients with IBD compared with matched controls. The primary outcome was the development of CAD events. Traditional and nontraditional CAD risk factors were assessed. Cox proportional hazards model was used to assess the impact of each CAD risk factor on the outcomes.RESULTS:A total of 356 IBD patients and 712 matched controls were followed for a median of 53 and 51 months, respectively. The unadjusted hazard ratio (HR) for developing CAD in the IBD group was 2.85 (95% confidence interval (CI) 1.82–4.46). IBD patients had significantly lower rates of selected traditional CAD risk factors (hypertension, diabetes, dyslipidemia, and obesity; P<0.01 for all). Adjusting for these factors, the HR for developing CAD between groups was 4.08 (95% CI 2.49–6.70). Among nontraditional risk factors, an elevated white blood cell (WBC) count was a risk factor for CAD development in the IBD group (HR 1.23; 95% CI 1.15–1.33).CONCLUSIONS:An increased incidence of CAD events was noted in IBD patients despite having a lower burden of traditional risk factors. Additionally, these risk factors had a lower impact on CAD development in the IBD group. Further investigation into how nontraditional risk factors, including WBC count, and the effect of attenuating systemic inflammation in IBD patients change CAD risk is warranted.

Review of the Evidence on Diagnosis of Deep Venous Thrombosis and Pulmonary Embolism

PURPOSE This review summarizes the evidence regarding the efficacy of techniques for diagnosis of deep venous thrombosis (DVT) and pulmonary embolism. METHODS We searched for studies using MEDLINE, MICROMEDEX, the Cochrane Controlled Trials Register, and the Cochrane Database of Systematic Reviews through June 2006. We reviewed randomized controlled trials, systematic reviews of trials, and observational studies if no trials were available. Paired reviewers assessed the quality of each included article and abstracted the data into summary tables. Heterogeneity in study designs precluded mathematical combination of the results of the primary literature. RESULTS Our review found 22 relevant systematic reviews and 36 primary studies. The evidence strongly supports the use of clinical prediction rules, particularly the Wells model, for establishing the pretest probability of DVT or pulmonary embolism in a patient before ordering more definitive testing. Fifteen studies support that when a D-dimer assay is negative and a clinical prediction rule suggests a low probability of DVT or pulmonary embolism, the negative predictive value is high enough to justify foregoing imaging studies in many patients. The evidence in 5 systematic reviews regarding the use of D-dimer, in isolation, is strong and demonstrates sensitivities of the enzyme-linked immunosorbent assay (ELISA) and quantitative rapid ELISA, pooled across studies, of approximately 95%. Eight systematic reviews found that the sensitivity and specificity of ultrasonography for diagnosis of DVT vary by vein; ultrasonography performs best for diagnosis of symptomatic, proximal vein thrombosis, with pooled sensitivities of 89% to 96%. The sensitivity of single-detector helical computed tomography for diagnosis of pulmonary embolism varied widely across studies and was below 90% in 4 of 9 studies; more studies are needed to determine the sensitivity of multidetector scanners. CONCLUSIONS While the strength of the evidence varies across questions, it is generally strong.

Blood Viscosity and Hematocrit as Risk Factors for Type 2 Diabetes Mellitus The Atherosclerosis Risk in Communities (ARIC) Study

Several lines of evidence support the notion that elevated blood viscosity may predispose to insulin resistance and type 2 diabetes mellitus by limiting delivery of glucose, insulin, and oxygen to metabolically active tissues. To test this hypothesis, the authors analyzed longitudinal data on 12,881 initially nondiabetic adults, aged 45–64 years, who were participants in the Atherosclerosis Risk in Communities (ARIC) Study (1987–1998). Whole blood viscosity was estimated by using a validated formula based on hematocrit and total plasma proteins at baseline. At baseline, estimated blood viscosity was independently associated with several features of the metabolic syndrome. In models adjusted simultaneously for known predictors of diabetes, estimated whole blood viscosity and hematocrit predicted incident type 2 diabetes mellitus in a graded fashion (Ptrend (linear) < 0.001): Compared with their counterparts in the lowest quartiles, adults in the highest quartile of blood viscosity (hazard ratio = 1.68, 95% confidence interval: 1.53, 1.84) and hematocrit (hazard ratio = 1.63, 95% confidence interval: 1.49, 1.79) were over 60% more likely to develop diabetes. Therefore, elevated blood viscosity and hematocrit deserve attention as emerging risk factors for insulin resistance and type 2 diabetes mellitus.

Improving the Informed Consent Process for Research Subjects with Low Literacy: A Systematic Review

ABSTRACTBACKGROUNDInadequate health literacy may impair research subjects’ ability to participate adequately in the informed consent (IC) process. Our aim is to evaluate the evidence supporting interventions, to improve comprehension of the IC process in low literacy subjects.METHODSWe performed a MEDLINE database search (1966 to November 2011) supplemented by manual searches of bibliographies of key relevant articles. We selected all studies in which a modification of the IC was tested to improve comprehension in low literacy populations. Study design, quality criteria, population, interventions and outcomes for each trial were extracted. The main outcome evaluated was comprehension, measured using a written test or verbal comprehension.RESULTSOur search strategy yielded 281 studies, of which only six met our eligibility criteria. The six studies included 1620 research participants. The studies predominantly included populations that were older (median age 61, range 48–64), ethnic minority, and with literacy level of 8th grade or below. Only one study had a randomized design. The specific intervention differed in each study. Two of the studies included the teach-back method or teach to goal method and achieved the highest level of comprehension. Two studies changed the readability level of the IC and resulted in the lowest comprehension among study subjects.CONCLUSIONSThe evidence supporting interventions to improve the informed consent process in low literacy populations is extremely limited. Among the interventions evaluated, having a study team member spend more time talking one-on-one to study participants was the most effective strategy for improving informed consent understanding; however, this finding is based on the results of a single study.

Large vessel involvement in ANCA-associated vasculitides: report of a case and review of the literature.

Vasculitides are currently classified according to the size of the vessels involved and characteristic clinical and histopathologic findings. Antineutrophil cytoplasmic antibodies (ANCA) and other serologic tests have been used to further characterize small vessel vasculitides. Large vessel involvement in ANCA-associated small vessel vasculitides has been overlooked in the medical literature. Here, we report a case of fatal aortitis and aortic dissection in a patient with microscopic polyangiitis and review reported cases of large vessel involvement in ANCA-associated vasculitides since 1990. We have attempted to characterize this subgroup of patients. Large vessel disease in ANCA-associated vasculitis may present as stenosing large vessel arteritis, aneurysmal disease, aortic dissection, aortic rupture, aortic regurgitation, and death. Prominent perivascular inflammation may present as mediastinal, cervical or abdominal soft tissue masses. ANCA-associated large vessel disease should be considered in the differential diagnosis of these disorders. The epidemiologic, clinical and pathologic characteristics of these patients differ from those of the well-defined large vessel vasculitides such as giant cell (temporal) arteritis or Takayasu’s arteritis. We suggest that large vessel involvement is part of the spectrum of ANCA-associated vasculitis rather than an overlap with other large vessel vasculitides. It occurs in both myeloperoxidase- and proteinase 3-positive patients with either Wegener’s granulomatosis or microscopic polyangiitis, but has not been reported in Churg–Strauss syndrome. Large vessel vasculitis can precede small vessel vasculitis or occur in the absence of small vessel involvement. We hope this report will contribute to the ongoing development of classification systems for the vasculitic syndromes.

Uric Acid as a Predictor of All-Cause Mortality in Heart Failure: A Meta-Analysis

Serum uric acid (SUA) is a product of xanthine oxidase (XO). Apoptosis and tissue hypoxia lead to increased purine catabolism, which, in turn, increases XO activity and subsequently SUA levels. The purpose of this study was to perform a meta-analysis to evaluate the evidence supporting SUA as a predictor of all-cause mortality in patients with heart failure (HF) and to determine the SUA cut-off for the increase in risk. A search of the MEDLINE database (1966 to March 2009) supplemented by manual searches of bibliographies of key relevant articles was performed. The authors selected all cohort studies in which SUA was measured and mortality was reported in patients with HF. The pooled relative risk (RR) with the corresponding 95% confidence interval (CI) for all-cause mortality using the fixed-effects method was calculated. The effects of SUA on all-cause mortality at different SUA cut-offs using meta-regression was evaluated. The search strategy yielded 358 studies, of which only 6 met our eligibility criteria. The studies, however, comprised 1456 evaluable patients with HF, with a median ejection fraction of 32% (range, 26%-40%). The RR of all-cause mortality was 2.13 (95% CI, 1.78-2.55) for SUA>6.5 mg/dL compared with <6.5 mg/dL SUA level. There was a linear association (P<.01) between SUA and mortality after 7 mg/dL. Uric acid is an important prognostic marker for all-cause mortality in HF. SUA levels >7 mg/dL are associated with higher all-cause mortality.

A systematic review of validated methods for identifying venous thromboembolism using administrative and claims data

Venous thromboembolism (VTE) is a serious complication. Large claims databases can potentially identify the effects that medications have on VTE. The purpose of this study is to evaluate the evidence supporting the validity of VTE codes.

Association of Serum Uric Acid With Incident Atrial Fibrillation (from the Atherosclerosis Risk in Communities [ARIC] Study)

Atrial fibrillation (AF) is one of the most common arrhythmias seen in clinical practice. Current evidence suggests that serum uric acid (SUA) could be a marker of oxidative damage, a factor reported as a part of the mechanisms of AF. The purpose of the present study was to evaluate whether SUA predicted AF in the Atherosclerosis Risk In Communities (ARIC) study. The present analysis included 15,382 AF-free black and white men and women, aged 45 to 64 years, from the ARIC study, a population-based prospective cohort in the United States. SUA was determined using the uricase-peroxidase method at baseline. The primary outcome was the incidence of AF, defined as the occurrence of AF detected using hospital discharge codes, scheduled study electrocardiograms, and/or death certificates during the follow-up period (1987 to 2004). We identified 1,085 cases of incident AF. In Cox proportional hazards models adjusted for age, gender, race, center, education, body mass index, serum glucose, systolic and diastolic blood pressure, low-density lipoprotein cholesterol, alcohol use, prevalent coronary heart disease and heart failure, serum creatinine, diuretics, and P-wave duration on the electrocardiogram (as a measure of left atrial size) at baseline, the hazard ratio of AF associated with a SD increment in SUA was 1.16 (95% confidence interval 1.06 to 1.26). The association of SUA with AF risk differed by race and gender (p for interaction <0.01). In conclusion, elevated SUA is associated with a greater risk of AF, particularly among blacks and women. Additional studies should replicate this association and explore potential mechanisms.