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Management of sickle cell disease.

BMJ. 2008;337:a1397

Authors: de Montalembert M

PMID: 18779222 [PubMed - indexed for MEDLINE]

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Treatment of Helicobacter pylori infection.

BMJ. 2008;337:a1454

Authors: Fuccio L, Laterza L, Zagari RM, Cennamo V, Grilli D, Bazzoli F

PMID: 18794181 [PubMed - indexed for MEDLINE]

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Bench-to-bedside review: the value of cardiac biomarkers in the intensive care patient.

Crit Care. 2008;12(3):215

Authors: McLean AS, Huang SJ, Salter M

The use of cardiac biomarkers in the intensive care setting is gaining increasing popularity. There are several reasons for this increase: there is now the facility for point-of-care biomarker measurement providing a rapid diagnosis; biomarkers can be used as prognostic tools; biomarkers can be used to guide therapy; and, compared with other methods such as echocardiography, the assays are easier and much more affordable. Two important characteristics of the ideal biomarker are disease specificity and a linear relationship between the serum concentration and disease severity. These characteristics are not present, however, in the majority of biomarkers for cardiac dysfunction currently available. Those clinically useful cardiac biomarkers, which naturally received the most attention, such as troponins and B-type natriuretic peptide, are not as specific as was originally thought. In the intensive care setting, it is important for the user to understand the degree of specificity of these biomarkers and that the interpretation of the results should always be guided by other clinical information. The present review summarizes the available biomarkers for different cardiac conditions. Potential biomarkers under evaluation are also briefly discussed.

PMID: 18557993 [PubMed - indexed for MEDLINE]

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Pharmacotherapy for heart failure with left ventricular dysfunction: beyond angiotensin-converting enzyme inhibitors and beta-blockers.

Pharmacotherapy. 2008 Jul;28(7):920-31

Authors: Norgard NB, Stark JE

Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers make up the cornerstone of therapy for patients with heart failure involving left ventricular dysfunction. These drug classes have been proven to decrease morbidity and mortality in patients with heart failure. Unfortunately, many patients remain symptomatic and experience disease progression despite taking both an ACE inhibitor and a beta-blocker. Others may be unable to tolerate one or both of these agents. In recent years, several other drug classes have been shown to provide additional morbidity and mortality benefits in patients with heart failure. These include angiotensin II receptor blockers (ARBs), aldosterone antagonists, and the combination of isosorbide dinitrate plus hydralazine. To select the most appropriate drug therapy for patients with heart failure, clinicians should consider results from clinical trials in specific patient populations, adverse-event profiles, tolerability, cost, and dosing regimens.

PMID: 18576907 [PubMed - indexed for MEDLINE]

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The effects of nesiritide on renal function and diuretic responsiveness in acutely decompensated heart failure patients with renal dysfunction.

J Card Fail. 2008 May;14(4):267-75

Authors: Owan TE, Chen HH, Frantz RP, Karon BL, Miller WL, Rodeheffer RJ, Hodge DO, Burnett JC, Redfield MM

BACKGROUND: Strategies to preserve renal function and enhance diuretic responsiveness during therapy for heart failure (HF) are needed. We hypothesized that brain natriuretic peptide (nesiritide) added to standard HF therapy would preserve renal function and enhance diuretic responsiveness. METHODS: Patients with HF with underlying renal dysfunction who were admitted with volume overload were randomized to standard therapy with nesiritide (2 mug/kg bolus; 0.01 mug/kg/min for 48 hours) or without nesiritide. Patients requiring intravenous vasodilator or inotropic therapy for rapid symptom relief were ineligible. In all patients, diuretics were administered according to a standardized dosing algorithm. RESULTS: Patients (n = 72) had a mean creatinine level of 1.75 +/- 0.59 mg/dL. Patients receiving nesiritide had a lesser increase in creatinine (P = .048) and blood urea nitrogen (P = .02), but a greater reduction in blood pressure (P < .01). Nesiritide did not enhance diuretic responsiveness (P = .57) but increased 3'5' cyclic guanosine monophosphate and decreased endothelin more (P < .05 for both). There were no differences in the change in atrial natriuretic peptide, N-terminal pro-brain natriuretic peptide, plasma renin activity, angiotensin II, and aldosterone between groups. CONCLUSION: When used as adjuvant "renal protective" therapy in patients with HF with renal dysfunction, the recommended dose of nesiritide reduced blood pressure, did not seem to worsen renal function, and suppressed endothelin but did not enhance diuretic responsiveness or prevent activation of the renin-angiotensin-aldosterone system.

PMID: 18474338 [PubMed - indexed for MEDLINE]

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Efficacy and safety of sevelamer hydrochloride and calcium acetate in patients on peritoneal dialysis.

Nephrol Dial Transplant. 2008 Sep 27;

Authors: Evenepoel P, Selgas R, Caputo F, Foggensteiner L, Heaf JG, Ortiz A, Kelly A, Chasan-Taber S, Duggal A, Fan S

BACKGROUND: Inadequate phosphorus control is associated with increased morbidity and mortality in patients with CKD stage 5. Although phosphate binders are often used in patients on peritoneal dialysis (PD), no large randomized controlled studies evaluating their use solely in this population have previously been reported. METHODS: In this multicentre, open-label study, adult patients on PD with serum phosphorus >5.5 mg/dl were randomized (2:1) to 12 weeks of treatment with sevelamer hydrochloride or calcium acetate. Doses were titrated to achieve serum phosphorus of 3.0-5.5 mg/dl. Changes in serum phosphorus, calcium, intact parathyroid hormone (iPTH), lipids and plasma biomarkers were assessed. RESULTS: A total of 253 patients were screened, 143 of whom were randomized (sevelamer hydrochloride, n = 97; calcium acetate, n = 46). Treatment groups were well balanced with regard to baseline demographics. Serum phosphorus levels were significantly reduced after 12 weeks with both sevelamer hydrochloride and calcium acetate (P < 0.001). Serum PTH was also reduced in both groups while serum calcium increased in the calcium acetate group (P = 0.001) but not in the sevelamer hydrochloride group. Sevelamer hydrochloride was also associated with decreases in total cholesterol, low-density lipoprotein cholesterol and uric acid and an increase in bone-specific alkaline phosphatase (all P < 0.001 versus baseline). Both treatments were well tolerated and safety profiles were consistent with previous reports in haemodialysis patients. Hypercalcaemia was experienced by more calcium acetate-treated patients (18 versus 2%; P = 0.001). CONCLUSIONS: In summary, sevelamer hydrochloride provides a reduction in serum phosphorus compared to that obtained with calcium-based binders in PD patients. The effects of sevelamer hydrochloride appear similar in both PD and haemodialysis populations.

PMID: 18820280 [PubMed - as supplied by publisher]

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Internal Medicine Training in the 21st Century.

Acad Med. 2008 Oct;83(10):910-915

Authors: Huddle TS, Heudebert GR

Many are calling for changes for internal medicine training, arguing that changes in the practice environment mandate changes in how the internal medicine residency is structured. Residency could be shorter, more conducive to role differentiation among general internists, and more supportive of subspecialization. Training could provide more experience in ambulatory care, multidisciplinary team-based care, chronic disease management, and quality improvement.The authors contend that the claim that internal medicine training ought to mirror internal medicine practice is mistaken. Many changes now proposed would likely damage if not destroy the consultant-generalist ideal of traditional internal medicine training which remains critical to effective medical care in the 21st century. The authors propose a model for training similar in structure but different in spirit from contending models. This model, like others, would involve a core experience in the first two years with tracking in the final year; unlike others, it would provide a conceptually coherent experience based on internal medicine’s traditional ideal. Outpatient experience would be subsidiary to a predominantly inpatient experience, and it would be structured in blocks rather than continuity clinics. Twenty-first-century internists will continue to face what has always been the internist’s task: the resolution of complex and ill-defined patient problems into proper diagnoses and therapeutic options. Contemporary internal medicine training must fit trainees for that task and must, thus, continue to offer the training experience necessary for the realization of the Oslerian ideal: a substantial apprenticeship taking care of inpatients with a wide range of medical illnesses.

PMID: 18820519 [PubMed - as supplied by publisher]

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Medication reconciliation effect on prolonged inpatient stress ulcer prophylaxis.

Ann Pharmacother. 2008 Jul;42(7):940-6

Authors: Zeigler AJ, McAllen KJ, Slot MG, Barletta JF

BACKGROUND: While medication reconciliation (MR) has been shown to reduce medication errors by limiting errors of transcription, omission, and duplicate therapy, its impact on the provision of unnecessary prophylaxis is largely unknown. OBJECTIVE: To determine the effect of MR on the incidence of prolonged stress ulcer prophylaxis (SUP) across the continuum of care from hospital admission to discharge as well as evaluate clinical conditions associated with prolonged SUP. METHODS: This retrospective study assessed patients who were admitted to the intensive care unit (ICU) and had SUP initiated. Patients were excluded if they were receiving gastroprotective therapy prior to ICU admission, were being treated for an acute gastrointestinal hemorrhage, or died. The need for SUP was determined using risk factors adapted from evidence-based guidelines developed by the American Society of Health-System Pharmacists. The use of SUP was assessed upon transfer from the ICU to a non-ICU setting and at hospital discharge. Results were compared between pre-MR and post-MR groups. RESULTS: Data from 114 (pre-MR, n = 53; post-MR, n = 61) medical and surgical ICU patients were evaluated. There was no significant difference in the use of prolonged SUP upon transfer from the ICU to a non-ICU setting in the pre-MR and post-MR groups, respectively (85% [45/53] vs 79% [48/61], p = 0.393). Similarly, there was no significant difference in the use of prolonged SUP upon hospital discharge in the pre-MR and post-MR groups, respectively (14% [6/44] vs 23% [10/43], p = 0.247). There were no clinical conditions for which prolonged SUP use was predominant. CONCLUSIONS: The strategy of MR alone will not decrease the incidence of prolonged SUP in hospitalized patients. Other techniques should be evaluated to encourage appropriate use of acid-suppressive agents.

PMID: 18577762 [PubMed - indexed for MEDLINE]

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Chronic obstructive pulmonary disease and deep vein thrombosis: a prevalent combination.

J Thromb Thrombolysis. 2008 Aug;26(1):35-40

Authors: Shetty R, Seddighzadeh A, Piazza G, Goldhaber SZ

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for venous thromboembolism (VTE). We analyzed a large US deep vein thrombosis (DVT) registry to explore the profile of patients with COPD and VTE. METHODS: Demographics, symptoms, risk factors, prophylaxis, and initial management of 668 (12%) patients with COPD were compared to 3,907 patients without COPD from a prospective registry of 5,451 consecutive patients with ultrasound-confirmed DVT at 183 institutions in the United States. RESULTS: COPD patients with DVT were older (median 72.5 years vs. 68.0 years, P < 0.0001) and more likely to be male (52.3% vs. 44.8%, P = 0.0004). They were more likely to be inpatients at the time of diagnosis of DVT (62.0% vs. 51.9%, P < 0.0001). COPD patients were more likely to be admitted to the intensive care unit (ICU) (27.7% vs.19.8%, P = 0.0003), more likely to require mechanical ventilation (23.2% vs. 13.6%, P < 0.0001), and more likely to receive inferior vena caval (IVC) filters (19.1% vs. 15.1%, P = 0.009). COPD patients more often had concomitant pulmonary embolism (PE) (22.8% vs.17.8%, P = 0.005) as well as concomitant congestive heart failure (29.5% vs. 12.5%, P < 0.0001). CONCLUSIONS: DVT patients with COPD have a greater medical acuity than other DVT patients. This results in more frequent IVC filter insertion.

PMID: 17940729 [PubMed - indexed for MEDLINE]

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Handheld echocardiography offers rapid assessment of clinical volume status.

Am Heart J. 2008 Sep;156(3):537-42

Authors: Nguyen VT, Ho JE, Ho CY, Givertz MM, Stevenson LW

BACKGROUND: Assessment of volume status is vital for successful management of patients in heart failure (HF) programs. Bedside determination of elevated left-sided filling pressure (LFP) can be challenging and frequently inaccurate; therefore, incorporating technology such as handheld echocardiography, to aid in estimation of LFP, may improve patient care. In this study, we evaluated the feasibility and accuracy of handheld echocardiography by a nonexpert for potential use in the point of care evaluation of compensation. METHODS: Subjects were recruited from the HF clinic or inpatient service at a single center. Each subject underwent a focused handheld transthoracic echocardiogram by a medical resident trained for 10 hours. Subjects were assigned to 1 of 4 filling patterns (1 = normal, 2 = abnormal relaxation, 3 = pseudonormal, 4 = restrictive) based on measurements by pulsed wave and tissue Doppler. A 3-step echocardiography test for congestion in HF (TEC-HF) was devised for estimation of LFP. The gold standard for determining elevated LFP was clinical evaluation by a HF specialist, who classified subjects as being euvolemic or hypervolemic. RESULTS: A total of 100 consecutive subjects (72% male) were recruited, with average age of 60 years and left ventricular ejection fraction of 27%. All subjects had evaluable echocardiographic data. Based on TEC-HF, filling patterns 3 and 4 predicted hypervolemia and patterns 1 and 2 predicted euvolemia, with sensitivity and specificity of 86% and 92%, respectively, and positive and negative predictive values of 86% and 92%, respectively. CONCLUSIONS: Applying TEC-HF with handheld echocardiography accurately reflects clinical LFP as assessed by HF specialists. This procedure was easily taught to nonexpert medical staff who obtained adequate images in all patients. Handheld echocardiography could be a useful tool for assessing volume status in nonspecialized community settings.

PMID: 18760138 [PubMed - indexed for MEDLINE]

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Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

JAMA. 2008 Sep 24;300(12):1439-50

Authors: Singh S, Loke YK, Furberg CD

CONTEXT: Inhaled anticholinergics (ipratropium bromide or tiotropium bromide) are widely used in patients with chronic obstructive pulmonary disease (COPD) but their effect on the risk of cardiovascular outcomes is unknown. OBJECTIVE: To ascertain the cardiovascular risks of inhaled anticholinergics, including cardiovascular death, myocardial infarction (MI), and stroke. DATA SOURCES: Systematic searches were conducted on March 19, 2008, of relevant articles in MEDLINE, the Cochrane Database of systematic reviews, regulatory authority Web sites in the United States and the United Kingdom, and manufacturers' trial registries with no date restrictions. STUDY SELECTION: Randomized controlled trials of any inhaled anticholinergic for treatment of COPD that had at least 30 days of treatment and reported on cardiovascular events. DATA EXTRACTION: The primary outcome was a composite of cardiovascular death, MI, or stroke. The secondary outcome was all-cause mortality. Relative risks (RRs) were estimated using fixed-effects models and statistical heterogeneity was estimated with the I(2) statistic. DATA SYNTHESIS: After a detailed screening of 103 articles, 17 trials enrolling 14 783 patients were analyzed. Follow-up duration ranged from 6 weeks to 5 years. Cardiovascular death, MI, or stroke occurred in 135 of 7472 patients (1.8%) receiving inhaled anticholinergics and 86 of 7311 patients (1.2%) receiving control therapy (RR, 1.58 [95% confidence interval {CI}, 1.21-2.06]; P < .001, I(2) = 0%). Among individual components of the primary end point, inhaled anticholinergics significantly increased the risk of MI (RR, 1.53 [95% CI 1.05-2.23]; P = .03, I(2) = 0%) and cardiovascular death (RR, 1.80 [95% CI, 1.17-2.77]; P = .008, I(2) = 0%) without a statistically significant increase in the risk of stroke (RR, 1.46 [95% CI, 0.81-2.62]; P = .20, I(2) = 0%). All-cause mortality was reported in 149 of the patients treated with inhaled anticholinergics (2.0%) and 115 of the control patients (1.6%) (RR, 1.26 [95% CI, 0.99-1.61]; P = .06, I(2) = 2%). A sensitivity analysis restricted to 5 long-term trials (>6 months) confirmed the significantly increased risk of cardiovascular death, MI, or stroke (2.9% of patients treated with anticholinergics vs 1.8% of the control patients; RR, 1.73 [95% CI, 1.27-2.36]; P < .001, I(2) = 0%). CONCLUSION: Inhaled anticholinergics are associated with a significantly increased risk of cardiovascular death, MI, or stroke among patients with COPD.

PMID: 18812535 [PubMed - in process]

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Ventilator-Associated Tracheobronchitis (VAT): The Impact of Targeted Antibiotic Therapy on Patient Outcomes.

Chest. 2008 Sep 23;

Authors: Craven DE, Chroneou A, Zias N, Hjalmarson K

Nosocomial lower respiratory tract infections are a common cause of morbidity and mortality in ventilated, intensive care unit (ICU) patients. Many studies have investigated the management and prevention of ventilator-associated pneumonia (VAP), but few have focused on the role of ventilator-associated tracheobronchitis (VAT). The pathogenesis of lower respiratory tract infections often begins with tracheal colonization that may progress to VAT, and in selected patients to VAP. Since there is no well established definition of VAT, discrimination between VAT and VAP can be challenging. VAT is a localized disease with clinical signs (fever, leukocytosis, and purulent sputum), microbiologic information (Gram stain with bacteria and leukocytes, with either a positive semi-quantitative or a quantitative sputum culture) and the absence of a new infiltrate on chest x-ray. Monitoring endotracheal aspirates has been used to identify and quantify pathogens colonizing the lower airway, to diagnose VAT or VAP, and to initiate early, targeted antibiotic therapy. Recent data suggest that VAT appears to be an important risk factor for VAP and that targeted antibiotic therapy for VAT may be a new paradigm for VAP prevention and better patient outcomes.

PMID: 18812452 [PubMed - as supplied by publisher]

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Prevalence of Pulmonary Embolism in Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis.

Chest. 2008 Sep 23;

Authors: Rizkallah J, Man SF, Sin DD

Background Nearly 30% of all exacerbations of chronic obstructive pulmonary disease (COPD) do not have a clear etiology. Although pulmonary embolism (PE) can exacerbate respiratory symptoms such as dyspnea and chest pain and COPD patients are at a high risk of PE due to a variety of factors including limited mobility, inflammation and co-morbidities, the prevalence of PE during exacerbations is uncertain. Methods A systematic review of the literature was performed to determine the reported prevalence of PE in acute exacerbations of COPD in patients who do and do not require hospitalization. The literature search was performed using MEDLINE, CINAHL, and EMBASE and complemented by hand searches of bibliographies. Only cross-sectional or prospective studies that used computed tomographic scanning or pulmonary angiogram for PE diagnosis was included. Results Of the 2407 articles identified, 5 met the inclusion criteria (sample size, 550 patients). Overall, the prevalence of PE was 19.9% (95% CI, 6.7% to 33.0%; p= 0.014). In hospitalized patients, the prevalence was higher at 24.7% (95% CI, 17.9% to 31.4%; p=0.001) than those who were evaluated in the emergency department (3.3%). Presenting symptoms and signs were similar between patients who did and did not have PE. Conclusions One out of four COPD patients who require hospitalization for an acute exacerbation may have PE. A diagnosis of PE should be considered in patients with exacerbation severe enough to warrant hospitalization, especially in those with an intermediate to high pre-test probability of PE.

PMID: 18812453 [PubMed - as supplied by publisher]

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Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke.

N Engl J Med. 2008 Sep 25;359(13):1317-29

Authors: Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D,

BACKGROUND: Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke. METHODS: After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. RESULTS: We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alteplase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P=0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P<0.05). The incidence of intracranial hemorrhage was higher with alteplase than with placebo (for any intracranial hemorrhage, 27.0% vs. 17.6%; P=0.001; for symptomatic intracranial hemorrhage, 2.4% vs. 0.2%; P=0.008). Mortality did not differ significantly between the alteplase and placebo groups (7.7% and 8.4%, respectively; P=0.68). There was no significant difference in the rate of other serious adverse events. CONCLUSIONS: As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage. (ClinicalTrials.gov number, NCT00153036.)

PMID: 18815396 [PubMed - in process]

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Drug-eluting or bare-metal stents for acute myocardial infarction.

N Engl J Med. 2008 Sep 25;359(13):1330-42

Authors: Mauri L, Silbaugh TS, Garg P, Wolf RE, Zelevinsky K, Lovett A, Varma MR, Zhou Z, Normand SL

BACKGROUND: Studies comparing percutaneous coronary intervention (PCI) with drug-eluting and bare-metal coronary stents in acute myocardial infarction have been limited in size and duration. METHODS: We identified all adults undergoing PCI with stenting for acute myocardial infarction between April 1, 2003, and September 30, 2004, at any acute care, nonfederal hospital in Massachusetts with the use of a state-mandated database of PCI procedures. We performed propensity-score matching on three groups of patients: all patients with acute myocardial infarction, all those with acute myocardial infarction with ST-segment elevation, and all those with acute myocardial infarction without ST-segment elevation. Propensity-score analyses were based on clinical, procedural, hospital, and insurance information collected at the time of the index procedure. Differences in the risk of death between patients receiving drug-eluting stents and those receiving bare-metal stents were determined from vital-statistics records. RESULTS: A total of 7217 patients were treated for acute myocardial infarction (4016 with drug-eluting stents and 3201 with bare-metal stents). According to analysis of matched pairs, the 2-year, risk-adjusted mortality rates were lower for drug-eluting stents than for bare-metal stents among all patients with myocardial infarction (10.7% vs. 12.8%, P=0.02), among patients with myocardial infarction with ST-segment elevation (8.5% vs. 11.6%, P=0.008), and among patients with myocardial infarction without ST-segment elevation (12.8% vs. 15.6%, P=0.04). The 2-year, risk-adjusted rates of recurrent myocardial infarction were reduced in patients with myocardial infarction without ST-segment elevation who were treated with drug-eluting stents, and repeat revascularization rates were significantly reduced with the use of drug-eluting stents as compared with bare-metal stents in all groups. CONCLUSIONS: In patients presenting with acute myocardial infarction, treatment with drug-eluting stents is associated with decreased 2-year mortality rates and a reduction in the need for repeat revascularization procedures as compared with treatment with bare-metal stents.

PMID: 18815397 [PubMed - in process]

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