Critical role of chemokine (C-C motif) receptor 2 (CCR2) in the KKAy + Apoe -/- mouse model of the metabolic syndrome.

AIMS/HYPOTHESIS: Chemokines and their receptors such as chemokine (C-C motif) receptor 2 (CCR2) may contribute to the pathogenesis of the metabolic syndrome via their effects on inflammatory monocytes. Increased accumulation of CCR2-driven inflammatory monocytes in epididymal fat pads is thought to favour the development of insulin resistance. Ultimately, the resulting hyperglycaemia and dyslipidaemia contribute to development of the metabolic syndrome complications such as cardiovascular disease and diabetic nephropathy. Our goal was to elucidate the role of CCR2 and inflammatory monocytes in a mouse model that resembles the human metabolic syndrome. METHODS: We generated a model of the metabolic syndrome by backcrossing KKAy ( + ) with Apoe ( -/- ) mice (KKAy ( + ) Apoe ( -/- )) and studied the role of CCR2 in this model system. RESULTS: KKAy ( + ) Apoe ( -/- ) mice were characterised by the presence of obesity, insulin resistance, dyslipidaemia and increased systemic inflammation. This model also manifested two complications of the metabolic syndrome: atherosclerosis and diabetic nephropathy. Inactivation of Ccr2 in KKAy (+) Apoe ( -/- ) mice protected against the metabolic syndrome, as well as atherosclerosis and diabetic nephropathy. This protective phenotype was associated with a reduced number of inflammatory monocytes in the liver and muscle, but not in the epididymal fat pads; circulating levels of adipokines such as leptin, resistin and adiponectin were also not reduced. Interestingly, the proportion of inflammatory monocytes in the liver, pancreas and muscle, but not in the epididymal fat pads, correlated significantly with peripheral glucose levels. CONCLUSIONS/INTERPRETATION: CCR2-driven inflammatory monocyte accumulation in the liver and muscle may be a critical pathogenic factor in the development of the metabolic syndrome.

[Total knee arthroplasty with ultracongruent tibial insert. Two-year follow-up]. / Artroplastía total de rodilla con inserto tibial ultracongruente. Seguimiento a dos años.

INTRODUCTION: There is no single criterion to select a posterior stabilization system for an arthroplasty; the ultracongruent system may avoid the complications observed with the drawer and the post. OBJECTIVE: To assess the clinical and functional status of total knee arthroplasty with the ultracongruent system and compare the results with those published in the international literature. MATERIAL AND METHODS: A retrospective study was carried out with a descriptive and comparative analysis of the total knee arthroplasties in which the Consensus system was used, to determine the operative time, the range of motion, pain, the Western Ontario and McMaster Universities Osteoarthritis Scale (WOMAC), and the level of satisfaction. RESULTS: Sixty-six arthroplasties were performed; mean age was 70.58 years; 45.5% were right and 54.5% left; the operative time was 76.84 minutes, the VAS pain score was 2.02, the WOMAC score was 17.11, and the range of motion was 96.5 +/- 14.04. Ninety-two percent of the patients are satisfied with the surgical procedure. CONCLUSIONS: The prosthesis with the ultracongruent insert is an effective option to relieve pain in patients with knee pathology. The clinical and functional results were similar to those reported with other stabilization systems. The system is well accepted by the patients. It is recommended as an alternative to prevent the possible complications that occur with the drawer and post system.

CCL2-independent role of CCR2 in immune responses against Leishmania major.

The chemokine CCL2 (MCP-1) and its receptor CCR2 modulate leucocyte migration and T helper differentiation. CCL2 or CCR2 knockout (KO) mice have divergent phenotypes following infection with the intracellular parasite Leishmania major (L. major). Compared to wild-type (WT) mice, intradermally infected CCR2 KO mice in the L. major-resistant C57BL/6j background become susceptible and fail to generate protective Th1 responses. In contrast, subcutaneously infected CCL2 KO mice in the L. major-susceptible BALB/c background are resistant and exhibit reduced pathogenic Th2 responses. Here we explore two variables that may account for this contrasting outcome, namely background strain and route of infection. We found that the CCR2-null state, both in the BALB/c and the C57BL/6j background, was associated with increased susceptibility to intradermal or subcutaneous L. major infection. Notably, the CCL2-null state did not change the ability of C57BL/6j mice to mount protective responses following intradermal infection. Dual genetic inactivation of CCR2 and CCL2 in the L. major-resistant C57BL/6j background resulted in a shift to a susceptible phenotype analogous to that of CCR2 KO in the C57BL/6j background. We concluded that CCL2-independent effects of CCR2 are indispensable for the control of L. major infection and the generation of protective immune responses.

A meta-analysis of the Papanicolaou smear and wet mount for the diagnosis of vaginal trichomoniasis.

PURPOSE: To obtain reliable estimates of the sensitivity and specificity of the cervical Papanicolaou (Pap) smear and wet mount to diagnose vaginal trichomoniasis. METHODS: Articles indexed in MEDLINE (1976-1998) about diagnostic tests for trichomoniasis and their listed references were retrieved. Thirty studies (9,501 patients) that used trichomonas culture as a gold standard were selected. Studies were defined as level I if they fulfilled at least two of the following three criteria: consecutive patients were evaluated prospectively, the decision to culture was not influenced by test results, and there was independent and blind comparison with culture. Studies were classified as level II if one criterion was fulfilled, and as level III otherwise. RESULTS: The pooled sensitivity of the Pap smear for the diagnosis of trichomoniasis among level I studies was 57% (95% confidence interval [CI]: 51% to 63%) and the pooled specificity was 97% (95% CI: 93% to 100%). The likelihood ratio for a positive Pap smear was 19 among level I studies (range: 8 to 62). The pooled sensitivity of the wet mount among level I studies was 58% (95% CI: 51% to 66%); among level II studies, the sensitivity was 72% (95% CI: 62% to 81%), and among level III studies, the sensitivity was 82% (95% CI: 67% to 97%). The overall specificity of the wet mount was 99.8%. CONCLUSIONS: A positive Pap smear for trichomonads in settings in which trichomoniasis is common (prevalence > or =20%) requires treatment. A positive Pap smear is indeterminate when the prevalence of trichomoniasis is about 10%; thus, clinicians should either confirm the diagnosis by culture or treat all such patients, recognizing that some patients will be treated unnecessarily. A culture should be obtained in women with a positive Pap smear who are unlikely to have trichomoniasis (prevalence < or =1%). While a positive wet mount is diagnostic, a negative wet mount does not exclude trichomoniasis.

Reporting and concordance of methodologic criteria between abstracts and articles in diagnostic test studies.

OBJECTIVE: To evaluate the quality and concordance of methodologic criteria in abstracts versus articles regarding the diagnosis of trichomoniasis. STUDY DESIGN: Survey of published literature. DATA SOURCES: Studies indexed in MEDLINE (1976-1998). STUDY SELECTION: Studies that used culture as the gold or reference standard. DATA EXTRACTION: Data from abstract and articles were independently abstracted using 4 methodologic criteria: (1) prospective evaluation of consecutive patients; (2) test results did not influence the decision to do gold standard; (3) independent and blind comparison with gold standard; and (4) broad spectrum of patients used. The total number of criteria met for each report was calculated to create a quality score (0-4). MEASUREMENTS AND MAIN RESULTS: None of the 33 abstracts or full articles reported all 4 criteria. Three criteria were reported in none of the abstracts and in 18% of articles (95% confidence interval [95% CI] 8.6% to 34%). Two criteria were reported in 18% of abstracts (95% CI, 8.6% to 34%) and 42% of articles (95% CI, 27% to 59%). One criterion was reported in 42% of abstracts (95% CI, 27% to 59%) and 27% of articles (95% CI, 15% to 44%). No criteria were reported in 13 (39%) of 33 abstracts (95% CI, 25% to 56%) and 4 (12%) of 33 articles (95% CI, 4.8% to 27%). The agreement of the criteria between the abstract and the article was poor (kappa -0.09; 95% CI, -0.18 to 0) to moderate (kappa 0.53; 95% CI, 0.22 to 0.83). CONCLUSIONS: Information on methods basic to study validity is often absent from both abstract and paper. The concordance of such criteria between the abstract and article needs to improve.

Cost-effectiveness of low-molecular-weight heparin in the treatment of proximal deep vein thrombosis.

OBJECTIVE: To estimate the cost-effectiveness of low-molecular-weight heparin (LMWH) in the treatment of proximal lower extremity deep venous thrombosis. DESIGN: Cost-effectiveness analysis that includes the treatment of the index case and simulated 3-month follow-up. SETTING: Acute care facility. PATIENTS AND PARTICIPANTS: Hypothetical cohorts of 1,000 patients who present with proximal deep venous thrombosis. INTERVENTIONS: Intravenous unfractionated heparin (UH), LMWH (40% at home, 60% in hospital), or selective UH/LMWH (UH for hospitalized patients and LMWH for patients treated at home). MEASUREMENTS AND MAIN RESULTS: The outcomes were recurrent thrombosis, mortality, direct medical costs, and marginal cost-effectiveness ratios from the payer's perspective. At the base-case and under most assumptions in the sensitivity analysis, the LMWH and the selective UH/LMWH strategies dominate the UH strategy i.e., they result in fewer cases of recurrent thrombosis and fewer deaths, and they save resources. The savings occur primarily by decreasing the length of stay. The LMWH strategy resulted in lower costs as compared with the UH strategy when the proportion of patients treated at home was more than 14%. Treating 1, 000 patients with the LMWH strategy as compared with the UH/LMWH strategy would result in 10 fewer cases of recurrent thrombosis, 1.2 fewer deaths, at an additional cost of $96,822; the cost-effectiveness ratio was $9,667 and $80,685 per recurrent thrombosis or death prevented, respectively. CONCLUSIONS: Treatment with LMWH leads to savings and better outcomes as compared with UH in patients with lower extremity deep venous thrombosis. The selective UH/LMWH strategy is an alternative option.

Evaluation of guidelines for the use of telemetry in the non-intensive-care setting.

To determine if the American College of Cardiology (ACC) cardiac monitoring guidelines accurately stratify patients according to their risks for developing clinically significant arrhythmias in non-intensive-care settings, we conducted a prospective cohort study of 2,240 consecutive patients admitted to a non-intensive-care telemetry unit over 7 months. Sixty-one percent of patients were assigned to ACC class I (telemetry indicated in most patients), 38% to class II (telemetry indicated in some), and 1% to class III (telemetry not indicated). Arrhythmias were detected in 13.5% of the class I patients, 40.7% of the class II patients, and 12% of the class III patients (p <.001). Telemetry detected an arrhythmia resulting in transfer to an intensive care unit in 0.4% of the class I patients, 1.6% of the class II patients, and none of the class III patients (p =.006). Telemetry led to a change in management for 3.4% of the class I patients, 12.7% of the class II patients, and 4% of the class III patients (p <.001). When patients with chest pain as the reason for admission were moved from class I to class II and patients with arrhythmias as the reason for admission were moved from class II to class I, more arrhythmias and more clinically significant arrhythmias occurred in class I patients and the trends from class I to class III were more consistent with the purpose of the guidelines. These findings indicate that when the ACC guidelines are reexamined, consideration should be given to changing them so they are more useful in non-intensive-care settings.

Anticoagulant patient information material is written at high readability levels.

BACKGROUND: Warfarin therapy requires frequent monitoring and dose adjustment. Elderly patients with atrial fibrillation, prior stroke, and lower literacy skills may have difficulty reading brochures that explain dosing instructions, procedures to follow, and the risks and benefits of anticoagulants. In general, it is recommended that brochures be written at or below the 6th-grade level. We determined the readability of patient information material being offered to patients receiving anticoagulants. METHODS AND RESULTS: We used the SMOG grade formula to measure readability of written patient materials. We obtained 50 brochures commonly used in anticoagulation management units from industry and health advocacy groups. Patient information was related to atrial fibrillation (16%, n=8), warfarin (44%, n=22), low-molecular-weight heparins (12%, n=6), or other related topics (28%, n=14). The mean readability was found to be grade 10.7 (95% CI 10.1 to 11.2); none had a readability score at the 6th-grade level or below, 12% of the brochures had readability scores at the 7th- to 8th-grade levels (n=6), 74% at the 9th- to 12th-grade levels (n=37), and 14% at higher than 12th-grade level (n=7). The readability grade level was similar for brochures produced by industry or health advocacy groups (P:=0.9) but higher for information obtained from the Internet (12.2+/-1.3 grades) compared with other sources (10.3+/-2.1 grades; P:=0.01). CONCLUSIONS: Patient education materials related to the use of anticoagulants are written at grade levels beyond the comprehension of most patients. Low-literacy brochures are needed for patients on anticoagulants.

Systematic review of diagnostic tests for vaginal trichomoniasis.

OBJECTIVE: To review critically and to summarize the evidence of diagnostic tests and culture media for the diagnosis of Trichomonas vaginitis. METHODS: We performed a systematic review of literature indexed in MEDLINE of studies that used Trichomonas culture as the reference standard (9,882 patients, 35 studies). Level I studies (5,047 patients, 13 studies) fulfilled at least two of three criteria: 1) consecutive patients were evaluated prospectively, 2) decision to culture was not influenced by test results, and 3) there was independent and blind comparison to culture. RESULTS: The sensitivity of the polymerase chain reaction technique (PCR) was 95% (95% CI 91% to 99%), and the specificity was 98% (95% CI 96% to 100%). One study was classified as Level I evidence (52 patients). The sensitivity of the enzyme-linked immunosorbent assay was 82% (95% CI 74% to 90%), and the specificity was 73% (95% CI 35% to 100%). The sensitivity of the direct fluorescence antibody was 85% (95% CI 79% to 90%), and the specificity was 99% (95% CI 98% to 100%). Sensitivities of culture media were 95% for Diamond's, 96% for Hollander, and 95% for CPLM. CONCLUSIONS: The sensitivity and specificity of tests to diagnose trichomoniasis vary widely.

Judging the effectiveness of clinical pathways for pneumonia: the role of risk adjustment.

CONTEXT: Although observational studies suggest that clinical pathways may decrease costs and improve quality in hospitalized patients with community-acquired pneumonia, inferences from these studies are limited by potential selection bias and inadequate case-mix adjustment. OBJECTIVE: To compare the assessment of a clinical pathway for community-acquired pneumonia with and without adjusting for patient characteristics and disease severity. DESIGN: Retrospective cohort study. PATIENTS AND SETTING: Consecutive series of adult patients admitted with clinical diagnosis of community-acquired pneumonia, treated with either a clinical pathway (which included guidelines for antibiotics, tests, and ancillary care) or usual care. MAIN OUTCOME MEASURES: Total hospital charges, length of stay, clinical deterioration (requiring mechanical ventilation or intensive care unit transfer), and in-hospital mortality. We used multiple linear and logistic regression to adjust for patient case mix. RESULTS: Compared with patients receiving usual care (n = 275), patients in the pathway group (n = 97) were more likely to be treated by family physicians than specialists and had lower pneumonia severity scores. In the unadjusted analysis, total hospital charges were lower among pathway patients ($2456; 95% CI, $175 to $4737; P = 0.04); in the adjusted analysis, the difference in total charges was smaller (average reduction $1807; CI, $4164 lower to $549 higher; P = 0.13). In the unadjusted analysis, length of stay was lower among pathway patients (1.8 days lower; CI, 3.9 lower to 0.4 higher; P = 0.12); in the adjusted analysis, the difference in length of stay was smaller (0.9 days lower; CI, 3.2 lower to 1.3 higher; P = 0.4). Although unadjusted analysis showed significantly lower in-hospital mortality in pathway patients, this difference was not confirmed in the adjusted analysis. CONCLUSIONS: Clinical pathways may reduce costs and improve quality of care in community-acquired pneumonia. In nonrandomized studies, however, selection bias and case-mix differences may explain some of the apparent effectiveness.

Asymptomatic patients at high risk for deep venous thrombosis who receive inadequate prophylaxis should be screened.

BACKGROUND: Patients after stroke and major orthopedic surgery have increased factors for developing deep vein thrombosis. We sought to determine the implications of screening high-risk patients to detect proximal deep vein thrombosis. METHODS: We used decision analysis to determine the implications of screening vs not screening asymptomatic high risk patients with duplex ultrasonography to detect proximal deep venous thrombosis. The outcomes were bleeding, pulmonary embolism, death, and number of patients with true-positive, false-positive, and false-negative tests. RESULTS: Screening with ultrasonography, all asymptomatic patients who receive appropriate prophylaxis, prevalence 5%, would result in the treatment of 3.1% patients with proximal deep vein thrombosis (true positives); 2.9% without proximal deep vein thrombosis (false positives) and in the lack of diagnosis in 1.9% patients (false negatives). At a prevalence of 20%, no prophylaxis, screening would result in the treatment of 12.4% patients with proximal deep vein thrombosis (true positives), 2.4% without proximal deep vein thrombosis (false positives), and in the lack of diagnosis in 7.6% of patients (false negatives). CONCLUSIONS: Screening high-risk patients who receive prophylaxis is not warranted. Patients who receive no prophylaxis should be screened with ultrasonography.

Role of telemetry monitoring in the non-intensive care unit.

To determine the outcomes of patients admitted to a non-intensive care telemetry unit and to assess the role of telemetry for guiding patient management decisions, data from 2,240 patients admitted to a telemetry unit were collected prospectively during 7 months. Physicians recorded the outcomes (intensive care unit transfer and mortality) and assessed whether telemetry assisted in guiding patient management. Indications for admission to the telemetry unit included chest pain syndromes (55%), arrhythmias (14%), heart failure (12%), and syncope (10%). Telemetry led to direct modifications in management in 156 patients (7%; 95% confidence interval [CI] 5.9% to 8%). Telemetry was perceived as useful but did not alter management for 127 patients (5.7%; 95% CI 4.7% to 6.6%). Two hundred forty-one patients were transferred to an intensive care unit from the telemetry unit (10.8%; 95% CI 9.5% to 12%). Nineteen patients (0.8% of all admissions; 95% CI 0.5% to 1.2%) were transferred because of an arrhythmia identified by telemetry. Routine transfer after cardiac revascularization or surgery accounted for 134 transfers; clinical deterioration accounted for 88 transfers. There were 20 deaths in the unit (0.9%; 95% CI 0.5% to 1.3%): 4 of the 20 deaths occurred while patients were being monitored. The role of telemetry in guiding patient management may be overestimated by physicians, since it detected significant arrhythmias that led to change in medications or urgent interventions in a small fraction of patients.

Outcomes of patients hospitalized to a telemetry unit.

To describe the clinical course of patients admitted to a nonintensive care telemetry unit and to determine whether telemetry identifies patients at risk for transfer to the intensive care unit (ICU), 467 patients hospitalized for cardiac monitoring in a nonintensive care telemetry unit were followed until death or discharge. The American College of Cardiology guidelines for telemetry use were applied: 65% of patients were class I (monitoring definitely indicated); 33% class II (probably indicated); and 2% class III (not indicated). In 5 patients (1%), telemetry contributed to the decision for a transfer to the ICU. In 462 patients, telemetry added no significant information. Thirty-eight patients (8.1%) were transferred to an ICU: 22 because of cardiac deterioration and 16 because of noncardiac clinical deterioration. Eighteen percent of patients in class I (95% confidence interval [CI], 14.1 to 22.8), 12% in class II (95% CI, 6.7 to 17), and none in class III (95% CI, 0 to 26) were transferred to the ICU (p = 0.03). Nine patients died (1.9%), 4 with terminal illness. Three patients died while on telemetry: 1 had metastatic lung cancer and 2 died suddenly of cardiac causes during initial evaluation on the ward. Telemetry identified the terminal rhythm in the 3 patients. Patients admitted to a non-ICU monitored ward with ischemic syndromes, heart failure, and arrhythmia rarely deteriorated. Patients who did deteriorate were recognized clinically without appreciable contribution from the monitoring process. It remains unproven that heart rhythm monitoring in general practice units improves patient care.

Patient preferences for novel therapy: an N-of-1 trial of garlic in the treatment for hypertension.

The authors used the N-of-1 clinical trial methodology to obtain insights about a patient's preference for garlic for the management of his hypertension. The 61-year-old man received garlic, 500 mg by mouth three times a day (3 weeks), or identical placebo (3 weeks) in three treatment pairs. While the patient was taking garlic the mean systolic blood pressure decreased by 2 mm Hg (95% confidence interval 0.4 to 4.7, p < 0.05), and the diastolic blood pressure decreased by 2.4 mm Hg (95% confidence interval 0.4 to 4, p < 0.025). The treatment effect of garlic was small, but the patient believed continuing garlic for the management of his hypertension was justified.

Antineutrophil cytoplasmic antibody associated with pulmonary hemorrhage: Wegener's granulomatosis?

Antineutrophil cytoplasmic antibodies have been described mainly in patients with Wegener's granulomatosis. It has proven useful for both diagnosis and follow-up in these patients. We have described a patient with diffuse pulmonary hemorrhage in whom the suspicion of Wegener's granulomatosis was raised by the identification of antineutrophil cytoplasmic antibodies.

Eosinophilic myositis an expression of L-tryptophan toxicity?

Eosinophilia-myalgia syndrome possibly due to L-tryptophan is a new clinical entity that has been recently reported. We describe the clinical presentation of eosinophilia, eosinophilic pustular folliculitis, myalgia, and eosinophilic myositis, that led to respiratory failure in a young man taking an L-tryptophan containing compound.

Esophageal involvement in secondary amyloidosis mimicking achalasia.

Amyloidosis is usually considered as a cause of motor disorders of the esophagus, including achalasia. However, most patients with amyloid in the esophagus are AL-type amyloid. We report what we believe is the fourth case of secondary amyloidosis (AA-type) resulting from rheumatoid arthritis. Clinically and radiologically the picture was that of achalasia.

Autoimmune hemolytic anemia and rheumatoid arthritis.

The incidence of AIHA in patients with rheumatoid arthritis has not been shown to exceed that in the general population. The prevalence of rheumatoid arthritis in patients with AIHA approximates that in the general population. On the basis of these data, it is extremely difficult to establish a relationship between AIHA and rheumatoid arthritis. The patient we have described had the unusual presentation of AIHA with rheumatoid arthritis. We believe the two remain distinct entities.