In uncomplicated, left-sided acute diverticulitis, observation did not differ from antibiotics for recovery

Transcription

1 Date of presentation: Presented By: Elham Kabiri 1396/1/20 Dr Elham Kabiri In uncomplicated, left-sided acute diverticulitis, observation did not differ from antibiotics for recovery Reference: Daniels L, Unlu C, de Korte N, et al; Dutch Diverticular Disease (3D) Collaborative Study Group. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg. 2017;104:52-61

2 Question In patients with a first episode of proven leftsided, uncomplicated acute diverticulitis, what is the effectiveness of observation compared with antibiotic treatment?

3 Methods v Patients:570 patients (median age 57 y, 51% men) who had a first episode of left-sided, uncomplicated acute diverticulitis, classified as modified Hinchey stages 1a or 1b (abscess 5 cm in size) or mild Ambrosetti diverticulitis stage, confirmed by computed-tomography within 24 hours. Exclusion criteria:previous confirmed diverticulitis, suspicion of colon can- cer, inflammatory bowel disease, antibiotic use in the previous 4 weeks, or expected survival < 6 months.

4 v Design:Randomized controlled trial (DIverticulitis: AntiBiotics Or close Observation [DIABOLO] trial). Setting: 22 surgical and gastroenterology departments in the Netherlands. Outcomes:Primary outcome was time to recovery. Secondary outcomes included hospital readmission; complicated, ongoing, and recurrent diverticulitis; sigmoid resection; and mortality.

5 Main results Groups did not differ for time to recovery, readmission, development of complications, or mortality (Table).

6 Table & figure

7 Conclusion In patients with a first episode of left-sided, uncomplicated acute diverticulitis, observation did not differ from antibiotic treatment for time to recovery or other clinical outcomes

8 Commentary v Most cases of diverticulitis are uncomplicated, with no significant long-term sequelae. Antibiotics have been the mainstay of therapy for diverticulitis, but the risk for adverse events (e.g., antibiotic resistance, Clostridium difficile infection) remains a concern. vto date, only a few studies have evaluated antibiotics for diverticulitis

9 Commentary v Based on these studies, the American Gastroenterological Association guideline suggests that antibiotics be used selectively in cases of uncomplicated diverticulitis and on an individual basis rather than routinely (5). vthe well-designed DIABOLO trial by Daniels and colleagues further supports that antibiotics are not always necessary in uncomplicated diverticulitis.

10 Commentary In this trial, groups did not differ for time to recovery, readmission, complications, or mortality. Although these findings are interesting, they need to be considered in context. Although the findings of Daniels and colleagues provide additional evidence that a conservative approach might be feasible in mild diverticulitis, further multicentered and multinational studies, including both left- and right-sided diverticulitis, are needed to clarify which patients can be managed without antibiotics.

11

12 Date of presentation: Presented By:Dr Kabiri In sepsis, continuous (vs intermittent) antibiotic infusion reduced hospital mortality Reference:A meta-analysis of individual patient data from randomized trials. Am J Respir Crit Care Med. 2016;194:

13 Question In critically ill patients with severe sepsis, how do continuous and intermittent infusions of -lactam antibiotics compare for mortality and clinical cure?

14 Methods v Patients: 632 critically ill patients (median age 61 to 63 y across treatments, 64% men) admitted to the intensive care unit (ICU) with severe sepsis. vdesign: Individual patient data meta-analysis of 3 randomized controlled trials (RCTs). Setting: Clinical centers in Australia, New Zealand, Hong Kong, and Malaysia. v Outcomes: Hospital mortality (censored at 30 d), ICU mortality, clinical cure (absence of signs and symptoms of infection at 7 to 14 d after cessation of study antibiotic), and ICU-free days at 28 days.

15 Main results Study drug was administered for a median of 5 days in the continuous group and 4 days in the intermittent group. Continuous infusion reduced hospital mortality, but not ICU mortality, com- pared with intermittent infusion (Table). Groups did not differ for clinical cure

16 Table & figure

17 Conclusion In critically ill patients with severe sepsis, continuous infusion of lactam antibiotics reduced hospital mortality compared with intermittent infusion; groups did not differ for clinical cure.

18 Commentary v Continuous infusion of antibiotics is believed to work by keep- ing drug levels consistently above a pathogen's minimum inhib- itory concentration, which is essential for killing bacteria v Plasma levels of hydrophilic antibiotics, such as piperacillin tazobactam and meropenem (given to 67% and 30% of patients in the included trials, respectively), can be reduced in sepsis due to increased volume of distribution from capillary leakage and from increased renal clearance that can occur in a hyper- dynamic state, such as sepsis

19 Commentary v Continuous infusion of -lactam antibiotics should not be broadly adopted for all patients with sepsis v Although a subgroup analysis found that APACHE II scores < 22 were associated with increased hospital survival and clinical cure, because the benefit of continuous in- fusion seems linked to the pathophysiology of severe sepsis the results cannot be confidently extrapolated to patients with less- than-severe sepsis or other infections.

20 Commentary v Implementing continuous infusion may affect work flow and cost. v Preparation of more infusions may burden hospital pharmacists. Although piperacillin tazobactam has 24-hour stability, meropenem is less stable and may require more frequent exchange of infusion bags. vthe need for more infusion pumps could incur additional cost. Continuous infusions may also require a dedicated IV line or lumen of a central venous catheter.

21

22 Date of presentation: Presented By: Dr Kabiri The USPSTF recommends low- to moderate-dose statins to prevent CVD in selected adults 40 to 75 years of age evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2016;316:

23 Question Can low 2 moderate-dose statins to prevent CVD in selected adults 40 to 75 years of age

24 Methods v Patients: adults 40 years of age without CVD Design: a systematic review, which searched MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews v Risk factors: (dyslipidemia, diabetes, hypertension, or smoking)

25 Main results 1. In adults 40 to 75 years of age with 1 risk factor for CVD and no history of CVD, the USPSTF recommended: a) Starting low- to moderate dose statins in patients with 10- year CVD risk 10% (grade B recommendation) b)with adults who have 10-year CVD risk 7.5% to 10% (grade Crecommendation ) c) In adults 76 years of age with no history of CVD, evidence was insufficient to make a recommendation for use of statins.

26 Table & figure

27 Conclusion The US Preventive Services Task Force recommends low- to moderate dose statins to prevent cardiovascular disease (CVD) in adults 40 to 75 years of age without CVD but with 1 risk factor and 10-year CVD risk 10%.

28 Commentary v The USPSTF recommendations for statins for primary prevention are similar to the 2013 ACC/AHA cholesterol treatment guidelines, with modest differences. The ACC/AHA set a treatment threshold at 10-year atherosclerotic CVD risk of 7.5%, whereas the USPSTF recommends that persons with 1 CVD risk factor

29 Commentary v The absolute benefit of statins, reflected in the number needed to treat, is clear but modest (at least over a 3-year period), but the risk for adverse events is low.

30 Commentary v Both the ACC/ AHA (1) and the USPSTF recommend treating patients at moderate or high risk for CVD with statins, regardless of cholesterol levels.

31 Commentary v clinicians should continue to prescribe statin therapy for primary prevention for patients at high or moderate risk for CVD and to have informed discussions with those at lower risk (10-y risk 5% to 10%), who may benefit from statin therapy in the long term.

32

33 Date of presentation: Presented By:Dr kabiri Different bisphosphonates are equally effective and safe for preventing fragility fractures A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures. Health Technol Assess. 2016;20:1-406

34 Question What are the effectiveness and safety of bisphosphonates for preventing fragility fractures?

35 Methods Patients: Included studies compared bisphosphonates with each other or control in women who were 65 years of age or 64 years of age with 1 risk factor, and men who were 75 years of age or 74 years of age with 1 risk factor Design: Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials Service Setting : 17 RCTs assessed alendronic acid, 12 assessed risedronic acid, 5 assessed ibandronic acid, 4 assessed zoledronic acid, 5 compared alendronic acid with risedronic acid, 1 compared alendronic acid with ibandronic acid,1 compared zoledronic acid with alendronic acid, and 1 compared zoledronic acid with risedronic acid.

36 v Risk factors: (low bone mass density [BMD], past fragility fracture, current or recent frequent use of glucocorticoids, previous falls, family history of hip fracture, other causes of secondary osteoporosis, body mass index < 18.5 kg/m2, or alcohol or smoking intake > 14 units/wk in women or > 21 units/wk in men v Outcomes: Outcomes included fragility fractures, mortality, and adverse events.

37 Main results Network meta-analysis showed that, compared with placebo, all bisphosphonates reduced vertebral fractures. Alendronic acid, risedronic acid, and zoledronic acid reduced nonvertebral fractures compared with placebo. No bisphosphonate differed from another for vertebral or nonvertebral fractures. Meta-analysis found that no bisphosphonate differed from another for mortality, upper gastrointestinal events, or withdrawal due to adverse events.

38 Table & figure

39 Conclusion Different bisphosphonates are equally effective for reducing risk for fragility fractures, and none increase risk for ortality or withdrawal more than others

40 Commentary All bisphosphonates reduce vertebral fractures, and most also reduce nonvertebral fractures. However, such well-recognized, rare adverse effects as osteonecrosis of the jaw (1) and atypical femur fractures (2) potentially limit their use.

41 Commentary v The Fracture Risk Assessment Tool (FRAX) is a clinical tool for assessing fracturerisk and can predict the potential benefit of therapy.

42 Commentary v The review by Davis and colleagues suggests that the choice of isphosphonate does not seem to affect efficacy. Patient convenience and availability favor the once-weekly regimen of alendronic acid or residronic acid

43 Commentary v Suggestions of a higher discontinuation rate in patients receiving generic bisphosphonates than branded bisphosphonates also warrant further investigation. vbecause cost of treatment nowadays largely depends on care of patients who experience serious adverse effects, the cost-effectiveness of bisphosphonates hinges on the rate of adverse events and fracture risk.

44 Image in clinical medicine NEW ENGLAND J. Of Medicine

45

46 Cullen sign

47

48 Regression of coronary Atherosclerosis with medical Therapy