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Update in Hospital Medicine Part I II

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Update in Hospital Medicine Part I II

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    1. Nilam J. Soni, MD Assistant Professor of Medicine University of Chicago David Friar, MD President, Hospitalists of Northern Michigan Traverse City, Michigan Update in Hospital Medicine Part I & II

    2. Methods Major medical journals from January 2010 to July 2011 Focus on breadth, not depth Details of key articles presented Case-based format Short-takes

    3. Case A 64-year old man with history HTN, OSA, CHF, hyperlipidemia and alcohol abuse presents with a 6 week history of worsening shortness of breath. Exam: Bilateral rales, 2+ bilateral lower extremityedema, and an irregularly irregular heart beat EKG: Atrial fibrillation with RVR (135 bpm) CXR: Pulmonary edema

    4. Case Diagnoses Acute decompensated heart failure Atrial fibrillation with rapid ventricular response (new-onset)

    5. Question In patients with acutely decompensated heart failure, a continuous IV infusion of furosemide is more effective at providing symptomatic relief when compared to IV bolus dosing.

    6. Infusion vs. Bolus Loop Diuretics for Heart Failure Felker GM, et al. Diuretic Strategies in Patients with Acute Decompensated Heart Failure. N Engl J Med 2011;364:797-805 Question: Are loop diuretics more effective when given as IV infusions vs. boluses in patients with acute decompensated heart failure? Design: Randomized, multicenter, double-blind study Outcome: Global assessment of symptoms, ? serum creatinine Participants: 308 patients, 26 hospitals, Cr <3.0 Patients were randomly assigned, in a 1:1:1:1 ratio, to either a low-dose strategy (total intravenous furosemide dose equal to their total daily oral loop diuretic dose in furosemide equivalents) or a high-dose strategy (total daily intravenous furosemide dose 2.5 times their total daily oral loop diuretic dose in furosemide equivalents) and to administration of furosemide either by intravenous bolus every 12 hours or by continuous intravenous infusion. Patients were randomly assigned, in a 1:1:1:1 ratio, to either a low-dose strategy (total intravenous furosemide dose equal to their total daily oral loop diuretic dose in furosemide equivalents) or a high-dose strategy (total daily intravenous furosemide dose 2.5 times their total daily oral loop diuretic dose in furosemide equivalents) and to administration of furosemide either by intravenous bolus every 12 hours or by continuous intravenous infusion.

    7. Results Felker GM, et al. Diuretic Strategies in Patients with Acute Decompensated Heart Failure. N Engl J Med 2011;364:797-805

    8. Results Felker GM, et al. Diuretic Strategies in Patients with Acute Decompensated Heart Failure. N Engl J Med 2011;364:797-805

    9. No significant difference in symptoms or change in serum creatinine at 72 hours Higher dose loop diuretic (2.5 times home oral dose) may improve symptoms faster but may also increase creatinine

    10. Case continued He receives furosemide 80mg IV in the ED Diltiazem 10mg IV is given to slow his heart rate and IV infusion is ordered He begins to show signs of respiratory fatigue, and you are concerned about impending respiratory failure. His oxygen saturation is 90% with a face mask with FiO2 of 50%.

    11. Question Which of the following statements is TRUE regarding treatment of acute cardiogenic pulmonary edema? Non-invasive ventilation (BiPAP, CPAP) vs. standard oxygen therapy are equally effective Nesiritide is preferred in hypotensive patients Nebulized albuterol gives symptomatic relief None of the above

    12. Short-take: Acute Cardiogenic Pulmonary Edema A multicenter, randomized controlled trial demonstrated significant improvement at 1 hour in dyspnea, heart rate, acidosis, and hypercapnia with non-invasive ventilation (CPAP, NIPPV) compared to standard oxygen therapy in patients with acute cardiogenic pulmonary edema. No significant differences in mortality or intubations.

    13. Short-take: Acute Cardiogenic Pulmonary Edema A meta-analysis of 31 randomized controlled trial comparing non-invasive ventilation with standard therapy found CPAP and BIPAP reduce intubations, and CPAP reduces mortality in acute cardiogenic pulmonary edema.

    14. Short-take: Nesiritide A randomized, placebo-controlled trial showed nesiritide improved dyspnea at 6 and 24 hours but also increased rates of hypotension. No significant difference in 30-day mortality, re-hospitalization, or worsening renal failure.

    15. Case continued His pulmonary edema resolves after 4 days of furosemide 80mg IV q8h, and his atrial fibrillation is fairly well controlled with metoprolol 50mg po bid. His heart rate fluctuates between 80 and 110 bpm but you are reluctant to increase his metoprolol because of potential hypotension.

    16. Question Strict heart rate control (<80 bpm) in patients with atrial fibrillation has been shown to decrease mortality compared to lenient heart rate control (<110). atrial fibrillation according to the 2006 ACC/AHA/ESC guidelines recommends strict heart rate control <80 but no data supporting improved QOL or morbidity or mortalityatrial fibrillation according to the 2006 ACC/AHA/ESC guidelines recommends strict heart rate control <80 but no data supporting improved QOL or morbidity or mortality

    17. Lenient vs. Strict Rate Control in Atrial Fibrillation Van Gelder I.C. et al. Lenient versus strict rate control in patients with atrial fibrillation. NEJM 2010;362:163-73. Question: Is lenient rate control (<110) inferior to strict rate control (<80) in patients with permanent atrial fibrillation? Design: Randomized, multicenter, noninferiority trial Outcome: Mortality (cardiac), hospitalization for CHF, CVA, systemic embolism, bleeding, life- threatening arrhythmias Participants: 614 patients, 33 hospitals, Age = 80

    18. Van Gelder I.C. et al. Lenient versus strict rate control in patients with atrial fibrillation. NEJM 2010;362:163-73.

    19. Lenient vs. Strict Rate Control in Atrial Fibrillation Van Gelder I.C. et al. Lenient versus strict rate control in patients with atrial fibrillation. NEJM 2010;362:163-73.

    20. Conclusions: Lenient vs. Strict Rate Control in Atrial Fibrillation Van Gelder I.C. et al. Lenient versus strict rate control in patients with atrial fibrillation. NEJM 2010;362:163-73. Lenient rate control (<110) is not inferior to strict rate control (<80) Lenient rate control does not increase risk of cardiac death, hospitalization for CHF, stroke, or bleeding Lenient rate control is easier to achieve.

    21. Case Continued Patient’s heart rate is maintained 80-110 bpm with metoprolol 50mg twice daily. You are ready to send him home, and family asks you, “When does he need to see his primary care doctor?”

    22. Short take: Follow-up in CHF A retrospective review of Medicare patients hospitalized for heart failure showed lower 30-day readmission rates when discharged from hospitals with higher early follow-up rates (<7 days).

    23. Case Presentation A 68 yo male with presents with 5 days of dyspnea and worsening cough. PMHX: COPD, dyslipidemia, HTN controlled with a beta blocker. Exam: Afebrile; SaO2=93% Resp: Decreased exchange with wheezes, & prolonged expiratory phase Chest x-ray: flattened diaphragms, but no infiltrates.

    24. What is the most appropriate management for COPD exacerbation? Prednisone 40mg daily but no antibiotics Prednisone 40mg daily and oral azithromycin Solumedrol 125mg Q6H but no antibiotics Solumedrol 125mg Q6H and oral azithromycin

    25. Association of Corticosteroid Dose and Route of Administration With Risk of Treatment Failure in Acute Exacerbation of COPD Lindenauer PK et al. JAMA. 2010;303:2359-2367. Question: What’s the optimal steroid dose and route in COPD exacerbation? Design: Cohort comparing 20-80 mg oral prednisone equivalent (PE) vs. 120-800 mg IV PE Outcome: Composite defined as initiation of mechanical ventilation at =2 days, inpatient mortality, or 30- day readmission for COPD Participants: Over 79K patients at 414 US hospitals Although RCTs show a benefit of steroids compared to placebo in AECOPD, the optimal dose and route of administration remains uncertain. Guidelines suggest use of oral steroid based on high bioavailability and extrapolating from studies investigating asthma. Cohort study using data from the Premier Incorporated Perspective, a voluntary fee supported database developed for measuring quality and healthcare utilization. Authors compared patients receiving 20-80 oral prednisone in first 2 days to patients receiving b/t 120-800 mg IV of equivalent of prednisone. Used a composite measure of… Over 79K patients hospitalized at 414 hospitals from 1/1/06 to 12/1/07. Patients included if >40 years of age, had a principal diagnosis of COPD or respiratory failure with COPD as a secondary diagnosis and were treated with corticosteroids during the first 2 days of hospitalization. Excluded patients admitted initially to the ICU and patients wih a secondary diagnosis of PE or pneumonia. Because this was an observational study, the authors used several different multivarible models in an attempt to control for confounders, including a propensity score which reflects a patient’s probability of initial treatment with low dose oral steroid. The authors used the propensity score in 2 ways. First, they included it as a covariate in a multivarible model and they also created a matched patients receiving low dose oral therapy with patients in the high dose IV group with a similar propensity score. Although RCTs show a benefit of steroids compared to placebo in AECOPD, the optimal dose and route of administration remains uncertain. Guidelines suggest use of oral steroid based on high bioavailability and extrapolating from studies investigating asthma. Cohort study using data from the Premier Incorporated Perspective, a voluntary fee supported database developed for measuring quality and healthcare utilization. Authors compared patients receiving 20-80 oral prednisone in first 2 days to patients receiving b/t 120-800 mg IV of equivalent of prednisone. Used a composite measure of… Over 79K patients hospitalized at 414 hospitals from 1/1/06 to 12/1/07. Patients included if >40 years of age, had a principal diagnosis of COPD or respiratory failure with COPD as a secondary diagnosis and were treated with corticosteroids during the first 2 days of hospitalization. Excluded patients admitted initially to the ICU and patients wih a secondary diagnosis of PE or pneumonia. Because this was an observational study, the authors used several different multivarible models in an attempt to control for confounders, including a propensity score which reflects a patient’s probability of initial treatment with low dose oral steroid. The authors used the propensity score in 2 ways. First, they included it as a covariate in a multivarible model and they also created a matched patients receiving low dose oral therapy with patients in the high dose IV group with a similar propensity score.

    26. 92% initially treated with high dose IV steroids Importantly, 92% of patients were initially treated with high dose IV steroids. Risk of treatment failure among patients who received low dose oral steroid was not significantly different from those treated with high-dose IV steroids. (lower OR would favor oral steroid, higher OR would favor IV steroid). Patients treated with oral steroids had shorter lengths of stay and lower costs. Shown is LOS and cost ratio for low dose oral:high dose IV steroid therapy.Importantly, 92% of patients were initially treated with high dose IV steroids. Risk of treatment failure among patients who received low dose oral steroid was not significantly different from those treated with high-dose IV steroids. (lower OR would favor oral steroid, higher OR would favor IV steroid). Patients treated with oral steroids had shorter lengths of stay and lower costs. Shown is LOS and cost ratio for low dose oral:high dose IV steroid therapy.

    27. Antibiotic Therapy and Treatment Failure in Patients Hospitalized for Acute Exacerbations of COPD Rothberg MB et al. JAMA. 2010;303:2035-2042. Question: Is early antibiotic treatment for COPD exacerbation associated with better outcomes? Design: Cohort study comparing abx in first 2 days vs. none/later Outcome: Composite defined as initiation of mechanical ventilation at =2 days, inpatient mortality, or 30-day readmission for COPD Participants: Over 84K patients at 413 hospitals Small RCTs show a benefit of antibiotic compared to placebo in AECOPD. Represents a total of only 917 patients included in these studies and only 1 prior study included patients treated with corticosteroids. These method will sound familiar, same research group. Cohort study using data from the Premier Incorporated Perspective, a voluntary fee supported database developed for measuring quality and healthcare utilization. Authors compared patients receiving at least 2 consecutive days of antibiotics initiated in first 2 hospital days with patients who received no antibiotics or received antibiotics after the 2nd hospital day. Abx included 1st, 2nd, and 3rd generation cephalosporins, quinolones, macrolides, tetracyclines, trimethoprim/sulfamethoxazole, and amoxocillin with or without clavulanci acid. Patients receiving other classes of abx on only a single dose of abx were excluded. Used a composite measure of… Over 79K patients hospitalized at 414 hospitals from 1/1/06 to 12/1/07. Patients included if >40 years of age, had a principal diagnosis of COPD or respiratory failure with COPD as a secondary diagnosis and were treated with corticosteroids during the first 2 days of hospitalization. Excluded patients admitted initially to the ICU and patients with a secondary diagnosis of PE or pneumonia. Because this was an observational study, the authors used several different multivariable models in an attempt to control for confounders, including a propensity score which reflects a patient’s probability of initial treatment with antibiotics vs. none/later. The authors used the propensity score in 2 ways. First, they included it as a covariate in a multivariable model and they also created a matched patients receiving early abx therapy with patients in the none/later group.Small RCTs show a benefit of antibiotic compared to placebo in AECOPD. Represents a total of only 917 patients included in these studies and only 1 prior study included patients treated with corticosteroids. These method will sound familiar, same research group. Cohort study using data from the Premier Incorporated Perspective, a voluntary fee supported database developed for measuring quality and healthcare utilization. Authors compared patients receiving at least 2 consecutive days of antibiotics initiated in first 2 hospital days with patients who received no antibiotics or received antibiotics after the 2nd hospital day. Abx included 1st, 2nd, and 3rd generation cephalosporins, quinolones, macrolides, tetracyclines, trimethoprim/sulfamethoxazole, and amoxocillin with or without clavulanci acid. Patients receiving other classes of abx on only a single dose of abx were excluded. Used a composite measure of… Over 79K patients hospitalized at 414 hospitals from 1/1/06 to 12/1/07. Patients included if >40 years of age, had a principal diagnosis of COPD or respiratory failure with COPD as a secondary diagnosis and were treated with corticosteroids during the first 2 days of hospitalization. Excluded patients admitted initially to the ICU and patients with a secondary diagnosis of PE or pneumonia. Because this was an observational study, the authors used several different multivariable models in an attempt to control for confounders, including a propensity score which reflects a patient’s probability of initial treatment with antibiotics vs. none/later. The authors used the propensity score in 2 ways. First, they included it as a covariate in a multivariable model and they also created a matched patients receiving early abx therapy with patients in the none/later group.

    28. Patients receiving early abx therapy had a lower risk for treatment failure as compared to patients who received no or later treatment. Patients receiving early abx therapy had a lower risk for treatment failure as compared to patients who received no or later treatment.

    29. In an attempt to discern whether certain antibiotics might be associated with lower rates of treatment failure, Rothberg and his colleagues published a subgroup analysis of this larger study comparing patients who had received quinolone therapy vs macrolide therapy. You can see that there is no significant difference in the rate of treatment failure between patients who received quinlones vs macrolides. There was a slight difference the in % of patients requiring mechanical ventilation later in their hospital stay and receiving antibiotics consistent with treatment for c difficule associated diarrhea favoring macrolides. It’s important to mention that 57% of the patients treated with macrolide wer also treated with a cephalosporin. The authors acknoledge that they are not sure to what extent the higher use of cephalosporins in the macrolide group may have affected outcomes. In an attempt to discern whether certain antibiotics might be associated with lower rates of treatment failure, Rothberg and his colleagues published a subgroup analysis of this larger study comparing patients who had received quinolone therapy vs macrolide therapy. You can see that there is no significant difference in the rate of treatment failure between patients who received quinlones vs macrolides. There was a slight difference the in % of patients requiring mechanical ventilation later in their hospital stay and receiving antibiotics consistent with treatment for c difficule associated diarrhea favoring macrolides. It’s important to mention that 57% of the patients treated with macrolide wer also treated with a cephalosporin. The authors acknoledge that they are not sure to what extent the higher use of cephalosporins in the macrolide group may have affected outcomes.

    30. Acute Exacerbation of COPD: Conclusions Use low dose oral steroid therapy Similar rate of treatment failure Lower LOS and cost Use early antibiotic therapy Lower rate of treatment failure Macrolides & quinolones have similar failure rate Use low dose oral steroid therapy. This is consistent with the guidelines. Interesting that 92% patients receiving high dose IV therapy. Use early antibiotic therapy. 21% patients not treated with early abx therapy. Finding is in agreement with prior small RCTs, but importantly only 1 prior RCT included patients treated with steroids and it didn’t show a benefit to abx. Macrolides and quinolones appear to have similar failure rate, but one has to take into account the high percentage of macrolide patients who also received a cephalosporin. Quinolones, as you know, are associated with a higher risk of CDAD. Use low dose oral steroid therapy. This is consistent with the guidelines. Interesting that 92% patients receiving high dose IV therapy. Use early antibiotic therapy. 21% patients not treated with early abx therapy. Finding is in agreement with prior small RCTs, but importantly only 1 prior RCT included patients treated with steroids and it didn’t show a benefit to abx. Macrolides and quinolones appear to have similar failure rate, but one has to take into account the high percentage of macrolide patients who also received a cephalosporin. Quinolones, as you know, are associated with a higher risk of CDAD.

    31. What is the most appropriate management for COPD exacerbation? Prednisone 40mg daily but no antibiotics Prednisone 40mg daily and oral azithromycin Solumedrol 125mg Q6H but no antibiotics Solumedrol 125mg Q6H and oral azithromycin

    32. Beta Blockers and COPD: Your patient has no history of CAD. Do you stop his beta blockers at time of discharge? Short et al, retrospective cohort study 6k, Scots with COPD over 4+ years. Endpoints: Mortality, emergency steroid use, respiratory admissions.

    33. Beta Blockers and COPD

    34. Beta Blockers and COPD

    35. Beta Blockers and COPD: No reason to stop beta blocker.

    36. Serological Testing Because of your enthusiasm and knowledge of COPD you were asked to help “update” your hospitals COPD admission order set. The ED doc wants everybody to have a BNP done. The ID doc wants everybody to have a pro-calcitonin level and urine pneumococcal antigen done. The lab director point out these tests are expensive.

    37. Serological Testing When the group turns to you for advice, you recommend: To add all these labs. To add none of these labs To add only a CRP That NPPs be allowed to park in the physician lot

    38. Serological Testing: B-type Natriuretic Peptide Lam et al, article review, 5 studies, 5 countries, 2513 patients Question: Does checking BNP at presentation to ED for acute SOB effect outcomes? Conclusion: BNP testing in the ED for patients presenting with acute dyspnea decreased length hospital of stay by about 1 day and possibly reduced admission rates but did not affect hospital mortality. Especially when done very early and in patients whom the diagnosis may not be clear. There is not likely to be an advantage to testing all patients admitted for COPD.

    39. Serological Testing: Strep. Pneumococcal urinary antigen Roger Sorde´, MD et al Question: What’s the role of pneumococcal antigen testing in CAP? Method: Prospective study of all adults hospitalized with CAP was performed from February 2007 through January 2008 in a British hospital Conclusion: When positive in patients with CAP it may allow the clinician to optimize antimicrobial therapy. This test would be appropriate for CAP patients, not all COPD patients.

    40. Serological Testing: Pro-calcitonin vx. C-Reactive Protein

    41. Serological testing: Pro-calcitonin vs C-Reactive Protein CHEST 2011; 139(6):1410–1418

    42. Serological Testing: Pro-calcitonin vx. C-Reactive Protein

    43. Speaking of CRP….

    44. Intermission

    45. Case Presentation A 54 year-old black male presents to ED with a 3 day history of fever/chills and generalized weakness PMH: HTN, ESRD Med’s: Amlodipine, labetalol, hydralazine ROS: Denies cough, abdominal pain, headache Vitals: T39.5 P116 BP 94/52 R28 Labs: WBC 18,000 with left shift

    46. Case Presentation ED Care: No obvious focal source of infection Blood cultures sent Vancomycin 1g IV and Piperacillin/Tazobactam 2.25g IV Blood pressure drops Normal saline 2L IV bolus Norepinephrine started for presumed septic shock Transferred to ICU

    47. Question A recent study demonstrated a reduction in mortality with norepinephrine vs. dopamine in treatment of patients with septic shock.

    48. Dopamine vs. Norepinephrine in Treatment of Shock DeBacker D. Et al. Comparison of dopamine and norepinephrine in the treatment of shock. NEJM 2010;362:779-89. Question: Which agent is superior in treatment of shock: dopamine or norepinephrine? Design: Multicenter, randomized study Outcome: Mortality at 28 days, need for organ support, adverse events Participants: 1,679 patients in shock, 8 hospitals

    49. Mortality Rates Dopamine vs. Norepinephrine in Shock DeBacker D. Et al. Comparison of dopamine and norepinephrine in the treatment of shock. NEJM 2010;362:779-89.

    50. 28-Day Survival Dopamine vs. Norepinephrine in Shock DeBacker D. Et al. Comparison of dopamine and norepinephrine in the treatment of shock. NEJM 2010;362:779-89.

    51. Subgroup Analysis Dopamine vs. Norepinephrine in Shock DeBacker D. Et al. Comparison of dopamine and norepinephrine in the treatment of shock. NEJM 2010;362:779-89.

    52. Conclusions Dopamine vs. Norepinephrine in Treatment of Shock DeBacker D. Et al. Comparison of dopamine and norepinephrine in the treatment of shock. NEJM 2010;362:779-89. Dopamine increased risk of arrhythmias, and higher mortality in cardiogenic shock subgroup. No significant difference in mortality with dopamine or norepinephrine in patients with septic or hypovolemic shock.

    53. Question Which of the following factors has the greatest impact on this patient’s survival? Delay in intubation Delay in transfer to ICU Selection of vasopressors Initiation of inappropriate antibiotics

    54. Initiation of Inappropriate Antibiotics in Septic Shock Kumar A et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 2009;135(5):1237-48. Question: What is the impact of initiation of inappropriate antibiotics on survival of patients with septic shock? Design: Retrospective, cohort study Outcome: Survival to discharge Participants: 5,715 patients in septic shock, 22 hospitals

    55. Impact of Antibiotic Appropriateness on Survival in Different Infections Kumar A et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 2009;135(5):1237-48.

    56. Conclusions Impact of Antibiotic Appropriateness on Survival Inappropriate empiric antibiotics reduced survival in all clinical subgroups Overall, survival decreased fivefold from 52% to 10.3% (OR 9.45, 95% CI 7.74-11.54;p<0.0001)

    57. Short Take: Antibiotic Selection A retrospective cohort study of patients with severe sepsis and septic shock due to Gram (-) rods showed an increased length of stay and increased mortality with initiation of inappropriate antibiotics.

    58. Case Continued Patient is stabilized in the ICU Lab reports positive blood cultures with Gram (+) cocci after 5 hours Vancomycin and piperacillin/tazobactam continued empirically Next morning lab reports 2/2 blood cultures with Staphylococcus aureus

    59. Question The medical student tells you that you should consult ID for the S. aureus bacteremia. Which of the following is the most appropriate response? Pretend you didn’t hear the medical student Consult ID and buy the medical student a cookie Wait for a couple to days to see how the patient does Tell the medical student to mind his own business and go read

    60. Infectious Diseases Consultation in S. aureus Bacteremia Honda H, et al. The value of infectious diseases consultation in Staphylococcus aureus bacteremia. The Americal Journal of Medicine 2010;123 (7):631-637 Question: What is the value of an infectious disease consult in patients with S. aureus bacteremia? Design: Prospective cohort study Outcome: All-cause mortality at 28 and 365 days Participants: 341 patients, =1 positive blood culture with S. aureus Done at a large tertiary care center in St. Louis. The diagnosis of S. aureus was defined as one or more blood cultures that were positive with clinical evidence of infection. 347 pts met criteria and 341 patients were analysed. Pts were tracked for 1 year reviewing medical records and social security death index. 3 ID teams involved and consultation was obtained at the discretion of the primary treating team. Done at a large tertiary care center in St. Louis. The diagnosis of S. aureus was defined as one or more blood cultures that were positive with clinical evidence of infection. 347 pts met criteria and 341 patients were analysed. Pts were tracked for 1 year reviewing medical records and social security death index. 3 ID teams involved and consultation was obtained at the discretion of the primary treating team.

    61. Results 341 pts were included and 54%(185) had MRSA. 110 (32%) were admitted to the ICU within 48hrs of detection. Only 111 (33%) had infectious disease consultations. The overall all cause 1 year mortality rate for patients with S. aureus bacteremia was 41%. (140/341)341 pts were included and 54%(185) had MRSA. 110 (32%) were admitted to the ICU within 48hrs of detection. Only 111 (33%) had infectious disease consultations. The overall all cause 1 year mortality rate for patients with S. aureus bacteremia was 41%. (140/341)

    62. Results Honda H, et al. The value of infectious diseases consultation in Staphylococcus aureus bacteremia. The Americal Journal of Medicine 2010;123 (7):631-637

    63. Conclusions Infectious Diseases Consultation in S. aureus Bacteremia Honda H, et al. The value of infectious diseases consultation in Staphylococcus aureus bacteremia. The Americal Journal of Medicine 2010;123 (7):631-637 Infectious diseases consultation was associated with a 56% reduction in 28-day mortality in patients with S. aureus bacteremia

    64. Short Take: Infectious Diseases Consultation in S. aureus bacteremia A retrospective cohort study of patients with S. aureus bacteremia showed a 36.4% decrease in 30-day mortality after implementing a program to consult infectious diseases for all patients with positive blood cultures with Gram (+) cocci in clusters.

    65. Case Continued ID consulted Hemodialysis catheter removed as suspected source Blood cultures grow methicillin-sensitive Staphylococcus aureus Patient afebrile at 48 hours and all repeat blood cultures (-) On hospital day 6, he develops diarrhea C. difficile toxin is positive

    66. Question Which of the following is NOT a risk factor for developing C. difficile infection? Intensive care unit stay Proton pump inhibitors Inflammatory bowel disease None of the above

    67. Gastric Acid Suppression and Nosocomial C. difficile Infection Howell, MD. Iatrogenic Gastric Acid Suppression and the Risk of Nosocomial Clostridium difficile Infection. Arch Intern Med. 2010;170(9):784-790. Question: Does gastric acid suppression increase the risk of C. difficile infection? Design: Retrospective cohort study Outcome: Nosocomial C. difficile infection Participants: 101,796 patients, >18 years, LOS > days, first episode C. difficile Done at a large tertiary care center in St. Louis. The diagnosis of S. aureus was defined as one or more blood cultures that were positive with clinical evidence of infection. 347 pts met criteria and 341 patients were analysed. Pts were tracked for 1 year reviewing medical records and social security death index. 3 ID teams involved and consultation was obtained at the discretion of the primary treating team. Done at a large tertiary care center in St. Louis. The diagnosis of S. aureus was defined as one or more blood cultures that were positive with clinical evidence of infection. 347 pts met criteria and 341 patients were analysed. Pts were tracked for 1 year reviewing medical records and social security death index. 3 ID teams involved and consultation was obtained at the discretion of the primary treating team.

    68. Gastric Acid Suppression and Nosocomial C. difficile Infection Howell, MD. Iatrogenic Gastric Acid Suppression and the Risk of Nosocomial Clostridium difficile Infection. Arch Intern Med. 2010;170(9):784-790.

    69. Gastric Acid Suppression and Nosocomial C. difficile Infection Howell, MD. Iatrogenic Gastric Acid Suppression and the Risk of Nosocomial Clostridium difficile Infection. Arch Intern Med. 2010;170(9):784-790.

    70. Conclusions Gastric Acid Suppression and Nosocomial C. difficile Infection Howell, MD. Iatrogenic Gastric Acid Suppression and the Risk of Nosocomial Clostridium difficile Infection. Arch Intern Med. 2010;170(9):784-790. Pharmacologic acid suppression is associated with increased risk of nosocomial C. difficile infection.

    71. Short Take: Proton Pump Inhibitors & Recurrent C. difficile Infection A retrospective cohort study demonstrated that recurrent C.difficile infection is more common in patients exposed to proton pump inhibitors than in those not exposed (25.2% vs 18.5%).

    72. Case Continued Diarrhea improves with metronidazole 500mg po tid Discharged with IV cefazolin x14 days and metronidazole x 10 days Over next 8 months, he has recurrent C. difficile infections He is treated with repeatedly with oral vancomycin which becomes less effective

    73. Question Which of the following is NOT a newer therapy for treating C. difficile infections? Ceftralocin Trandolomicin Fidaxomicin Intravenous immunoglobulin

    74. Fidaxomicin vs. Vancomycin for C. difficile Infection Louie TJ. Fidaxomicin versus Vancomycin for Clostridium difficile Infection. New England Journal of Medicine. 364(5):422-431. Question: Is fidaxomicin as effective as vancomycin for treating C. difficile infection? Design: Randomized, non-inferiority trial Outcome: Clinical cure, recurrent CDI, global cure Participants: 629 adult patients, excluded IBD or recent C.difficile infection, life-threatening infection Patients received the study medication orally each day for 10 days, according to an every-6-hour regimen: 200 mg of fidaxomicin every 12 hours with intervening matching doses of placebo or 125 mg of vancomycin every 6 hours. Patients received the study medication orally each day for 10 days, according to an every-6-hour regimen: 200 mg of fidaxomicin every 12 hours with intervening matching doses of placebo or 125 mg of vancomycin every 6 hours.

    75. Fidaxomicin vs. Vancomycin for C. difficile Infection Louie TJ. Fidaxomicin versus Vancomycin for Clostridium difficile Infection. New England Journal of Medicine. 364(5):422-431.

    76. Conclusions Fidaxomicin vs. Vancomycin for C. difficile Infection Howell, MD. Iatrogenic Gastric Acid Suppression and the Risk of Nosocomial Clostridium difficile Infection. Arch Intern Med. 2010;170(9):784-790. Clinical cure rates are similar with fidaxomicin versus oral vancomycin for C. difficile infection Less recurrence of C. difficile infection in patients treated with fidaxomicin but in only in subgroup with non–North American Pulsed Field type 1 strains

    77. Short Take: Monoclonal Antibodies for Treatment of C. difficile Infection A phase 2 trial showed significantly reduced recurrence of C. difficile infection (7% vs. 25%, p<0.001) in patients treated with monoclonal antibodies in addition to standard therapy with metronidazole or oral vancomycin.

    78. Case: 58 year old male with obesity, tobacco use and HTN controlled with an lisinopril, presents with 2.5 hours of acute onset R sided hemiplegia and marked aphasia. His significant other indicates he has always said he wanted aggressive treatment and would never want to live if debilitated. The ED says it will take at least 45 minutes to get the pre-TPA work up done and he will be out of the < 3 hour window by then.

    79. Case continued: You, Tell him he’s not a candidate for TPA and admit him on the stroke pathway. Tell the patient he should have lost weight and quit smoking years ago and recommend hospice Tell the ED to get cracking… times a wasting and you think he would be a good candidate for TPA despite being over 3 hours. Give TPA now without the pre TPA work up.

    80. The scores on the modified Rankin scale indicate the following: 0, no symptoms at all; 1, no significant disability despite symptoms (able to carry out all usual duties and activities); 2, slight disability (unable to carry out all previous activities but able to look after own affairs without assistance); 3, moderate disability (requiring some help but able to walk without assistance); 4, moderately severe disability (unable to walk without assistance and unable to attend to own bodily needs without assistance); 5, severe disability (bedridden, incontinent, and requiring constant nursing care and attention); 6, death.The scores on the modified Rankin scale indicate the following: 0, no symptoms at all; 1, no significant disability despite symptoms (able to carry out all usual duties and activities); 2, slight disability (unable to carry out all previous activities but able to look after own affairs without assistance); 3, moderate disability (requiring some help but able to walk without assistance); 4, moderately severe disability (unable to walk without assistance and unable to attend to own bodily needs without assistance); 5, severe disability (bedridden, incontinent, and requiring constant nursing care and attention); 6, death.

    81. Stroke: Thrombolytics Jeffrey Saver et al, ECASS III was a double-blind, parallel-group trial that enrolled patients from multiple centers across Europe, 228 patients. Question: Is it safe to give TPA at 3-4.5 hours. Results: NNTB for improved final outcome was 6.1 (95% CI, 5.6- 6.7) NNTH 37.5 (95% CI, 34.6-40.5). Benefit per 100 patients treated was 16.3 and harm per 100 was 2.7. The likelihood of help to harm ratio was 6.0. Conclusions: TPA in the 3-4.5 hour window confers benefit on half as many patients as <3 hours, with no increase in the conferral of harm. Approximately 1 in 6 patients has a better and 1 in 35 has a worse outcome as a result of therapy. European Cooperative Acute Stroke StudyEuropean Cooperative Acute Stroke Study

    82. Case continued: Stroke Before you can get the pre-TPA check list completed the ED provider asks you if you’d rather have an MRI than a CT to evaluate for ischemic stroke, “it’s the latest thing in Europe” You: (By show of hands) Order a stat MRI instead of a stat CT You remind him their isn’t time to get an MRI so you’ll have to do it the “American way”

    83. Stroke: Question: What role should MRI play in initial work up of acute CVI? American Academy of Neurology; Evidence-based guideline: The role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke; systematically analyzed the literature from 1966 to January 2008 RECOMMENDAT IONS: 1) DWI should be considered superior to noncontrast CT scan for the diagnosis of acute ischemic stroke in patients presenting within 12 hours of symptom onset. (sensitivity is not 100% and is probably closer to 80%–90%) 2) If DWI not immediately available or can’t be done in time to allow thrombolytic use, use non-contrast CT. diffusion weighed (edema) good evidence Perfusion weighted, (typically used) (blood flow in capillary) not as good of evidencediffusion weighed (edema) good evidence Perfusion weighted, (typically used) (blood flow in capillary) not as good of evidence

    84. Case Continued: Your stroke protocol calls for TED hose to help decrease DVT incidence. The nurse calls because the patient doesn’t want to wear thigh high TED hose. By show of hands: You want thigh highs anyway Knee highs are just as good

    85. TED hose: the higher the better Question: Thigh-Length Versus Below-Knee Stockings for Deep Venous Thrombosis Prophylaxis After Stroke The CLOTS (Clots in Legs Or sTockings after Stroke) Trial Collaboration, Parallel-group trial in 112 hospitals, 9 countries, 3114 patients Conclusion: Proximal DVT occurs more often in patients with stroke who wear below-knee stockings than in those who wear thigh-length stockings. US to eval for symptomatic or asymptomatic DVT Measurements: Ultrasonographers performed compression duplex ultrasonography in 1406 patients (96% of survivors) in each treatment group between 7 and 10 days after enrollment. They performed a second scan in 643 patients in the thigh-length stockings group and 639 in the below-knee stockings group at about 25 to 30 days. The primary outcome was symptomatic or asymptomatic DVT in the popliteal or femoral veins, detected on either scan. US to eval for symptomatic or asymptomatic DVT Measurements: Ultrasonographers performed compression duplex ultrasonography in 1406 patients (96% of survivors) in each treatment group between 7 and 10 days after enrollment. They performed a second scan in 643 patients in the thigh-length stockings group and 639 in the below-knee stockings group at about 25 to 30 days. The primary outcome was symptomatic or asymptomatic DVT in the popliteal or femoral veins, detected on either scan.

    86. TED hose: the higher the better US to eval for symptomatic or asymptomatic DVT Measurements: Ultrasonographers performed compression duplex ultrasonography in 1406 patients (96% of survivors) in each treatment group between 7 and 10 days after enrollment. They performed a second scan in 643 patients in the thigh-length stockings group and 639 in the below-knee stockings group at about 25 to 30 days. The primary outcome was symptomatic or asymptomatic DVT in the popliteal or femoral veins, detected on either scan. US to eval for symptomatic or asymptomatic DVT Measurements: Ultrasonographers performed compression duplex ultrasonography in 1406 patients (96% of survivors) in each treatment group between 7 and 10 days after enrollment. They performed a second scan in 643 patients in the thigh-length stockings group and 639 in the below-knee stockings group at about 25 to 30 days. The primary outcome was symptomatic or asymptomatic DVT in the popliteal or femoral veins, detected on either scan.

    87. Case Continued: Your stroke dose well with TPA, his aphasia clears entirely and he is left only with mild left sided strength deficit. He is discharged home with outpatient PT/OT. The medical student working with you asks about continuing his enoxaparin after he goes home because he is still at increased risk for VTE events.

    88. Case Continued: You: Pat the medical student on the head and recommend they go into psychiatry. Stroke your chin thoughtfully and order home enoxaparin for a month. Explain that this patient is not a good candidate for prolonged VTE prophylaxis. Start the patient on full dose coumadin.

    89. Extended-Duration Venous Thromboembolism Prophylaxis in Acutely Ill Medical Patients With Recently Reduced Mobility Question: What is the efficacy and safety of extended- duration enoxaparin in the prevention of VTE in medical patients? Design: RCT comparing enoxaparin to placebo given for 28 days after discharge Outcome: Benefit to high risk female and older patients, but some harm to lower risk patients Participants: 6085 patients from 370 hospitals and 20 countries were randomized.

    90. Extended Duration Enoxaparin Results

    91. Case continued: 2 weeks later your obese stroke patient returns to the ED with a right lower extremity DVT. You admit him on IV unfractionated heparin (UFH) using: Weight based UFH dosing normogram WITH a capped bolus and infusion dose. Weight based UFH dosing normogram but WITHOUT a capped bolus and infusion dose. Weight based UFH dosing normogram but at a reduced rate because bleeding is always a worry. A non-weight based dosing for UFH.

    92. DVT: Dosing of heparin in obese Adam Hurewitz et al, 3 years, New York academic hospital, consecutive case series. 84 Adult inpatients with VTE and BMI =30 kg/m2 treated with unfractionated heparin. Findings: 89% had prescribed bolus doses less than guideline recommended dose (80 u/kg) 76% the initial infusion dose was more than 100 units/hr less than guideline dose. % who didn’t reach therapeutic anticoagulation within: 24 hrs = 43% 48 hrs = 14% Each decrease of 1 unit/kg/h translated to a delay ranging from about 0.75 h to 1.5 h over the range of prescribed doses (6 to 22 units/kg/h).

    93. Case continued: Despite your best efforts your stroke patient returns with shortness of breath and is found to have a large PE. You rush to the ED, and find they have not yet started anticoagulation. You: Write ward orders and tell the nurses to start heparin when the pt gets upstairs. You have the nurse start heparin stat in the ED. You start rivaroxaban 10 mg daily. You thank the patient for being such a great annuity and delay admission while you check the 4 Winns’ web to look for a bigger boat.

    94. PE: Timing is everything

    95. PE: Timing is everything

    96. PE: Timing is everything

    97. Case: You are discharging a 68 yo female after THA. She still smokes and though has never had a VTE event, had a sister die of PE after an surgical procedure. At time of discharge she asks about the “new pill to stop clots”, you: Tell her it’s not approved for use after hip surgery. Tell her you she’s too low of a risk to send home on VTE prophylaxis. Tell her you only use warfarin. Write her a prescription for rivaroxaban 10mg daily for 35 days.

    98. New anticoagulant agents: FDA Approves Another Anticoagulant Newest warfarin alternative could be a "game-changer," thrombosis expert says A once-daily dose of rivaroxaban 10 mg, an oral, direct Factor Xa inhibitor, was compared with enoxaparin 40 mg subcutaneously once daily for prevention of venous thromboembolism in three studies of patients undergoing elective hip and knee replacement (RECORD programme). A pooled analysis of data from these studies (n = 9581) showed that rivaroxaban was more effective than enoxaparin in reducing the incidence of the composite of symptomatic venous thromboembolism and all-cause mortality at two weeks (0.4% vs 0.8%, respectively, odds ratio 0.44; 95% confidence interval 0.23 to 0.79; p = 0.005), and at the end of the planned medication period (0.5% vs 1.3%, respectively; odds ratio 0.38; 95% confidence interval 0.22 to 0.62; p < 0.001). The rate of major bleeding was similar at two weeks (0.2% for both) and at the end of the planned medication period (0.3% vs 0.2%). Rivaroxaban started six to eight hours after surgery was more effective than enoxaparin started the previous evening in preventing symptomatic venous thromboembolism and allcause mortality, without increasing major bleeding.A once-daily dose of rivaroxaban 10 mg, an oral, direct Factor Xa inhibitor, was compared with enoxaparin 40 mg subcutaneously once daily for prevention of venous thromboembolism in three studies of patients undergoing elective hip and knee replacement (RECORD programme). A pooled analysis of data from these studies (n = 9581) showed that rivaroxaban was more effective than enoxaparin in reducing the incidence of the composite of symptomatic venous thromboembolism and all-cause mortality at two weeks (0.4% vs 0.8%, respectively, odds ratio 0.44; 95% confidence interval 0.23 to 0.79; p = 0.005), and at the end of the planned medication period (0.5% vs 1.3%, respectively; odds ratio 0.38; 95% confidence interval 0.22 to 0.62; p < 0.001). The rate of major bleeding was similar at two weeks (0.2% for both) and at the end of the planned medication period (0.3% vs 0.2%). Rivaroxaban started six to eight hours after surgery was more effective than enoxaparin started the previous evening in preventing symptomatic venous thromboembolism and allcause mortality, without increasing major bleeding.

    99. New anticoagulant agents: FDA says Rivaroxaban (Xarelto), Xa inhibitor Once a day for 12 days for TKA, 35 days for THA Start 6-8 hours after surgery Dabigatran(Pradaxa ) direct thrombin inhibitor 150mg bid for CVI prophylaxis in non-valvular afib

    100. New anticoagulant agents: Studies say… DVT use Oral Rivaroxaban for Symptomatic Venous Thromboembolism The EINSTEIN Investigators Open-label, randomized, noninferiority study that compared oral rivaroxaban alone with subcutaneous enoxaparin followed by a vitamin K antagonist. AND a double-blind, randomized, superiority study that compared rivaroxaban alone with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. Conclusions: Rivaroxaban offers a single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation. The New England Journal of Medicine Issue: Volume 363(26), 23 December 2010, p 2499–2510

    101. New anticoagulant agents: Studies say… DVT use The New England Journal of Medicine Issue: Volume 363(26), 23 December 2010, p 2499–2510

    102. New anticoagulant agents: Studies say… DVT use The New England Journal of Medicine Issue: Volume 363(26), 23 December 2010, p 2499–2510

    103. Case: You are asked to see a patient who is scheduled for TKA in the preop clinic. The patient has a history of MRSA, you are asked whether they should be check for MRSA carriage and decontaminated if positive You say: No, too many people are carriers to try and decontaminate them. It won’t change anything for their knee surgery. You screen them for MRSA because if positive decontamination is a good idea. You screen them but only to isolate them, not to try and decontaminate them.

    104. Surgery stuff: MRSA Does decontamination of MRSA carriers improve surgical outcomes? Bode, Lonneke G.M. M.D. et al,  screened 6771 patients were screened for S. aureus in the nasal passages. 1251 were positive (18.8%). Patients were decontaminated with mupirocin-chlorhexidine. The New England Journal of Medicine Issue: Volume 362(1), 7 January 2010, p 9–17

    105. Surgery stuff: MRSA The New England Journal of Medicine Issue: Volume 362(1), 7 January 2010, p 9–17

    106. Surgery stuff: Conclusion: This study shows that rapid detection of S. aureus nasal carriage followed by immediate decolonization of nasal and extranasal sites with mupirocin nasal ointment and chlorhexidine gluconate soap significantly reduced the risk of hospital-acquired S. aureus infections in patients at risk. This intervention also significantly reduced the mean hospital stay by almost 2 days. Cautionary note: Be sure your institution is prepared to deal with 1 in 5 patients needing MRSA isolation on the surgical ward and that somebody is ready to counsel the patients and family about MRSA. The New England Journal of Medicine Issue: Volume 362(1), 7 January 2010, p 9–17

    107. Surgery stuff: The patient you are seeing in the preop clinic is a diabetic. How important is it to control their post operative glucose? Ashar Ata et al, retrospective review of 2090 general and vascular surgical cases what factors increased risk of site infection, age, emergency status, physical status, operative time, more than 2 U of RBC transfused, preoperative glucose level higher than 180 mg/dL , diabetes mellitus, and postoperative hyperglycemia Conclusion: Postoperative hyperglycemia may be the most important risk factor for SSI in general surgical patient. Op time was more important in the vascular cases. Limitation: The fact that hyperglycemia was associated with increased SSI doesn’t mean that it is a cause, or that tight control won’t bring it’s own risks for poor outcomes. Archives of Surgery, Vol 145, No 9, Sep 2010

    108. Enteral vs TPN in pancreatitis How does enteral feeding compare with TPN in acute pancreatitis? Paul E Marik, Gary P Zaloga; lit search and review of 6 trials with 263 patients Acute pancreatitis results in a hypermetabolic, hyperdynamic, systemic inflammatory response syndrome that creates a highly catabolic stress state. Despite the lack of prospective data, gut rest (prohibiting enteral intake) with or without the provision of parenteral nutrition has become regarded as standard care in patients with acute pancreatitisAcute pancreatitis results in a hypermetabolic, hyperdynamic, systemic inflammatory response syndrome that creates a highly catabolic stress state. Despite the lack of prospective data, gut rest (prohibiting enteral intake) with or without the provision of parenteral nutrition has become regarded as standard care in patients with acute pancreatitis

    109. Enteral vs. TPN in pancreatitis Conclusion: Enteral nutrition reduces mortality, multiple organ failure, systemic infections, and operative interventions more than total parenteral nutrition in patients with acute pancreatitis. and should be the nutrition method of choice.

    110. Acknowledgements Teri Kellogg Kristina Lishawa Jina Saltzman Sharon Kulesz

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