Day: 02/23/2013

Tuberculosis.

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In 2011, there were 8.7 million new cases of active tuberculosis worldwide. Recent advances in diagnostics, drugs, and vaccines and enhanced implementation of interventions are helping to improve the prospects for global tuberculosis control. The latest review in our Current Concepts series covers the diagnosis and treatment of latent, active, and drug-resistant tuberculosis and also reviews new drugs and vaccines.

Despite the availability of a cheap and effective cure, tuberculosis remains responsible for millions of active tuberculosis cases and deaths worldwide, disproportionately affecting the poorest in both high-income and developing countries. Recent advances in new diagnostics, drugs, and vaccines and enhanced implementation of existing interventions now provide optimism for improved clinical care and prospects for global tuberculosis control.

Clinical Pearls

•  What are the clinical manifestations of tuberculosis?    

The classical clinical features of pulmonary tuberculosis include chronic cough, sputum production, appetite loss, weight loss, fever, night sweats, and hemoptysis. Extrapulmonary tuberculosis (EPTB) occurs in 10 to 42% of cases, depending on ethnic background, host, M. tuberculosis strain genotype, and immune status. EPTB can affect any organ in the body, has varied and protean clinical manifestations, and requires a high index of clinical suspicion.

•  How does coinfection with HIV affect the risk for and presentation of tuberculosis? 

The risk of active tuberculosis disease increases soon after infection with HIV and the manifestations of pulmonary tuberculosis at this stage are similar to those in HIV-negative persons. At CD4 counts <200 per cubic millimeter, the presentation of tuberculosis may be atypical, with subtle infiltrates, pleural effusions, hilar lymphadenopathy, and other forms of EPTB in as many as 50% of patients. At CD4 counts <75 per cubic millimeter, pulmonary findings may be absent and disseminated tuberculosis is more frequent, presenting as a non-specific chronic febrile illness with widespread organ involvement, mycobacteremia, and high early mortality. Cases may be mistakenly diagnosed as other infectious diseases, and are often only identified by autopsy. Asymptomatic, smear-negative, culture-positive, chest X-ray negative, subclinical tuberculosis is a common feature of HIV-associated tuberculosis and may represent 10% of cases in endemic regions.

Morning Report Questions

Q: What tests are available for diagnosing active tuberculosis? 

A: Sputum microscopy and culture in liquid media with subsequent drug susceptibility testing (DST) are current recommended standard tuberculosis diagnostics. Solid culture media are more cost-effective in resource poor countries. Interferon gamma release assays an tuberculin skin tests have no role in the diagnosis of active tuberculosis disease. Nucleic acid amplification tests (NAATs), imaging, and histopathological examination of biopsies supplement these evaluations. The new molecular diagnostic test Xpert MTB/RIF assay detects M. tuberculosis complex rapidly in 2 hours with assay sensitivity much higher than smear microscopy. In HIV-patients it yields up to a 45% increase in tuberculosis case detection compared with smear microscopy.

Q: How does tuberculosis coinfection affect the treatment of HIV?

A: Tuberculosis leads to CD4+ cell activation and accelerated progression of HIV disease with attendant high mortality. Early initiation of antiretroviral therapy (ART) results in reduction of mortality and AIDS-defining conditions; short-term mortality risk without ART is high for those with very low CD4+ cell counts. WHO recommends that ART be started within the first eight weeks of initiating tuberculosis treatment, and that those with CD4+ counts <50 cells should receive ART within the first two weeks. One exception is tuberculosis meningitis where earlier ART initiation does not improve outcomes and results in more adverse events. Immune reconstitution inflammatory syndrome (IRIS) occurs in at least 5 to 10% of HIV-infected patients starting ART during tuberculosis treatment. This includes both “unmasking IRIS” (new active tuberculosis detected after ART initiation) and “paradoxical IRIS” (clinical worsening during tuberculosis treatment after ART initiation). IRIS is more common with lower CD4+ cell counts and at earlier ART initiation during tuberculosis treatment, with rates approaching 50% among patients with CD4+ cell count <50 and ART initiation within 4 weeks of beginning tuberculosis treatment.

Source:NEJM

Comparing Scoring Systems to Predict Outcomes in Upper Gastrointestinal Bleeding.

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AIMS65 better predicted mortality and Glasgow-Blatchford better predicted the need for transfusion, but both scoring systems can be helpful in identifying high-risk patients with UGIB.

Investigators recently derived and validated AIMS65 — a new scoring system to predict outcomes for patients with acute upper gastrointestinal bleeding (UGIB) — using a large population of patients from 187 U.S. hospitals (JW Gastroenterol Dec 9 2011).

Now, the researchers have revalidated AIMS65 using data on 278 UGIB patients from a tertiary-care hospital who had a higher severity of disease than that observed in the original population. They also compared the performance of AIMS65 with that of the Glasgow-Blatchford system (GBS; JW Gastroenterol Jul 29 2011) in predicting the primary outcome of inpatient mortality and several secondary outcomes: the composite endpoint of mortality, rebleeding, and endoscopic, radiologic, or surgical intervention; transfusion requirement; intensive care unit admission; rebleeding; length of hospital stay; and the timing of endoscopy.

Overall inpatient mortality was 6.5%. The composite endpoint was seen in 35%. AIMS65 was superior to GBS for predicting mortality (area under the receiver operating curve, 0.93 vs. 0.68; P<0.001), but GBS was superior for predicting the need for transfusion (AUROC, 0.85 vs. 0.65; P<0.01). The two systems were similarly accurate for predicting and other secondary outcomes. GBS values of 10 and 12 maximized the accuracy for predicting mortality and rebleeding, respectively. AIMS65 values of ≥2 maximized the accuracy for predicting both outcomes.

Comment: Results of this study from a tertiary-care hospital with expertise in treating patients with upper gastrointestinal bleeding might not be generalizable to other settings. What seems clear from the evidence regarding UGIB scoring systems is that shock, advanced age, and comorbid conditions used in any scoring system can identify patients at high risk for adverse outcomes. However, the issue is not about which system is better; rather, it is about ensuring that some system is used to identify high-risk patients, who will benefit from urgent endoscopy, endoscopic therapy, and more aggressive care, and low-risk patients, who can be treated as outpatients.

Source: Journal Watch Gastroenterology

 

New Surviving Sepsis Campaign Guidelines Released.

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These updated guidelines for management of severe sepsis and septic shock are based on broad agreement among a large group of international experts.

Background and Purpose: While evidence remains weak for many aspects of care, these guidelines, updated from 2008 and developed independent of industry funding, represent the most up-to-date international consensus for optimal resuscitation of septic patients.

Key Points:

Resuscitation Goals in First 6 Hours

  • Central venous pressure 8 to 12 mm Hg (grade 1C)
  • Mean arterial pressure (MAP) ≥65 mm Hg (grade 1C)
  • Urine output ≥0.5 mL/kg/hour (grade 1C)

Antimicrobials

  • Intravenous administration within 1 hour of recognition of septic shock (grade 1B) and severe sepsis without septic shock (grade 1C)

Fluids

  • Crystalloids as first choice for initial fluid resuscitation (grade 1B)
  • Initial minimum crystalloid challenge of 30 mL/kg (grade 1C)

Vasopressors and Inotropes

  • Norepinephrine as first choice (grade 1B) with epinephrine added or potentially substituted when adequate blood pressure cannot be maintained (grade 2B)
  • Phenylephrine not recommended except if norepinephrine is associated with serious arrhythmias, if cardiac output is high and blood pressure persistently low, or as salvage therapy when MAP target is not achieved (grade 1C)
  • Dobutamine infusion trial up to 20 µg/kg/minute administered or added to vasopressor in the case of myocardial dysfunction or ongoing signs of hypoperfusion (grade 1C)

Corticosteroids

  • No corticosteroids in the absence of refractory shock (grade 1D)

Blood Products

  • After tissue hypoperfusion is corrected, red blood cell transfusion only when hemoglobin concentration decreases to <7.0 g/dL, to a target hemoglobin concentration of 7.0–9.0 g/dL in adults (grade 1B)

Comment: Severe sepsis and septic shock require rapid identification and initiation of resuscitative measures. These guidelines, although based more on expert consensus than on evidence, should be familiar to all providers who care for patients with severe infections and used to guide initial treatment considerations.

Source: Journal Watch Emergency Medicine