1、General Medicine Update,Minnesota ACP November, 2010 Steve Hillson General Internal Medicine Hennepin County Medical Center University of Minnesota s_,Objectives,At the end of this session you should be able to: Describe the main results of several important reports from the past year Decide how you
2、 want to change your practice in the context of these findings,Disclosure,I have no direct financial relationships with any commercial firm having any interest in any of the reports or topics I am about to discuss.,Process,Personally reviewed title of every original research article from 10/08/09 ti
3、ll 10/15/10 in: Annals of Internal Medicine BMJ JAMA Lancet New England Journal of Medicine American Journal of Medicine Reviewed subspecialty updates, scattered other sources Personally reviewed abstract of every article with “interesting” title.,Process (contd),Selected “promising” articles by ini
4、tial abstract review (about 100) Re-reviewed all abstracts, selecting about 50 with medium or high impact potential Solicited abstract reviews from colleagues to select subset of greatest importance Critically appraised final subset for presentation,Limitations on Process,Personal idiosyncrasies Inc
5、omplete survey of medical literature No claim to comprehensive context for assessing these articles Very simplified presentation of complex research,Blood Pressure,How aggressive should we be for high-risk patients? 3 Important Articles Effects of intensive blood-pressure control in type 2 diabetes
6、mellitus (ACCORD), NEJM, April 2010 Funded by the NIH, medicines contributed by various pharmaceutical companies Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease, JAMA, July 2010 Funded by a pharmaceutical company Intensiv
7、e blood-pressure control in hypertensive chronic kidney disease, NEJM, September 2010 Funded by NIH and pharmaceutical companies,Purpose,Assess whether cardiovascular outcomes can be improved by aggressive blood pressure control Previous information Cardiovascular risk rises throughout the range of
8、systolic BPs JNC 7 recommends medical treatment of SBP to below 130 Some recommendations for even tighter control in especially high risk circumstances, particularly with chronic kidney disease,#1 ACCORD substudy,Compare tighter (SBP120) to looser (SBP140) BP control in type 2 diabetes Clinical Tria
9、l, unblinded 4733 patients with DM-2, over age 40 with CV disease or risk factors, Creatinine 1.5, SBP 130-180 and 1 gram proteinuria Received standard BP medications titrated to 120 OR 140 Also were enrolled in ACCORD glycemic control study Followed up to 8 years for MI, stroke, cardiovascular deat
10、h,#2 INVEST follow-up,Designed to compare two drug strategies with target BP of 130 Follow-up compares patients who achieved SBP130 to those who did not Cohort study 6400 diabetic patients with hypertension and CAD, in many countries Initially received ACEI plus either Ca- or B-blocker Followed at l
11、east 2.5 years for MI, CVA or death,#3 AASK,African-American study of kidney disease and hypertension Compare intensive (MAP 92, 116/80) to standard (MAP 102-107, 135/85-140/90) BP control RCT with cohort phase, 1094 African Americans with HBP, CKD, and mild or no diabetes Received ACEI, B-blocker o
12、r Ca blocker as first agent Added furosemide, doxazosin, clonidine, hydralizine Followed up to 12 years, including cohort period, for death, ESRD, or doubling creatinine,Findings,Additional Findings,In ACCORD, intensive therapy reduced non-fatal strokes slightly In INVEST, uncontrolled BP (over 140)
13、 was associated with much worse outcomes In AASK, patients with some baseline proteinuria did benefit from intensive control,Limitations,In ACCORD, standard therapy yielded better than expected outcomes INVEST, as a cohort study of achieved blood pressure, could be biased. For example, the best cont
14、rolled patients were on the fewest drugs AASK used a strange BP control strategy,Implications,Three studies suggest intensive BP control is not better in 3 different high-risk groups Guidelines recommending intensive control need to be reviewed Tight BP control might not be as important as using goo
15、d drugs and managing multiple risk factors Im planning to ease up a little bit EXCEPT in non-diabetic CKD patients with proteinuria,Atrial Fibrillation,Lenient versus strict rate control in patients with atrial fibrillation I.C. van Gelder, et al, for “RACE-II” NEJM, April 2010,Purpose,Determine whe
16、ther strict rate control of atrial fibrillation is necessary Background For most patients with a. fib, rate control is equivalent or superior to rhythm control Existing guidelines recommend strict rate control to improve symptoms, heart failure, and survival. These guidelines lack an evidence base F
17、unded by Netherlands heart foundation and pharmaceutical and device makers,Method,Randomized clinical trial, unblinded 614 Dutch patients In permanent atrial fibrillation 80, on anticoagulation or aspirin Used B-blockers, Ca-blockers, Dig to achieveStrict control (P 80 at rest, 110 with moderate exe
18、rcise) OR Lenient control (P110 at rest) Followed 3 years for CV for composite of CV death, stroke, CHF, bleeding, embolism, arrhythmias, pacers, defibrillators,Results,Limitations,3 year follow-up Rate-related complications could possibly take longer to develop Relatively active, low-risk group But
19、 subanalysis of higher risk subjects was the same Unblinded opportunity for different behaviors I do not see it,Implications,Guidelines for rate control in atrial fibrillation need to be re-assessed At least in lower risk patients over 3 years, strict rate control may offer no evident advantage I wi
20、ll ease up my efforts to control rate in A Fib.,Hepatic Encephalopathy,Rifaximin treatment in hepatic encephalopathy NM Bass et al. NEJM, March 2010 Funded by makers of rifaximin, authors received money and several are employed or on the board,Purpose,Establish whether rifaximin can improve maintena
21、nce of remission from hepatic encephalopathy Background information Rifaximin previously shown effective for treating acute cirrhosis-related hepatic encephalopathy Very limited trial evidence of any chronic treatment (including lactulose) Rifaximin recently released in US,Method,Randomized clinical
22、 trial, blinded 299 patients in Russia, Canada, US Cirrhosis and at least 2 episodes encephalopathy, in remission No CRF or other major illness Received Rifaximin 550 mg bid OR placebo Lactulose permitted, not required Followed 6 months for new episode of encephalopathy,Results,NNT for one hospitali
23、zation for HE = 11 for 6 months,Limitations,Subjects not required to take lactulose 10% of control group received no preventive treatment for hepatic encephalopathy Price of Rifaximin is stunning 1 month = $1,300 $85,000 to prevent one hospitalization for HE,Implications,Rifaximin is effective for p
24、reventing hepatic encephalopathy in patients with cirrhosis and prior HE. Whether it is superior to properly used lactulose is unproven Rifaximin is extraordinarily expensive Lactulose costs 94% less I will use rifaximin, but only in patients who are clearly failing lactulose therapy,COPD Exacerbati
25、ons,Antibiotic therapy and treatment failure in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease MB Rothberg et al. JAMA, May 2010 Funding not reported No apparent commercial funding,Purpose,Determine whether giving antibiotics to patients hospitalized for COPD
26、exacerbations improves outcomes Background Information ACP recommends antibiotics for patients with increased or purulent sputum Only relatively small, older trials support this,Method,Cohort study using large multi-hospital database 84,000 hospital discharges for COPD in US Age at least 40, not adm
27、itted to ICU, not discharged within 2 days, not diagnosed with bacterial infection Assessed whether at least 2 days of antibiotic given Followed for mechanical ventilation, inpatient mortality, 30-day readmission,Results,Of 84,621 hospitalizations for COPD: 79% received antibiotics within first 2 da
28、ys Antibiotics were MORE commonly used in patients who Were white Had no recent COPD admissions Did not have heart failure Lived in the South Went to non-teaching hospitals Got ABGs and IV steroids,More Results,NNT to prevent 1 death = 200,Limitations,Database study Insufficient detail to determine
29、why subjects did/didnt get antibiotics Cohort Study Obvious confounding opportunities Might expect more seriously ill patients to receive antibiotics Did not identify subgroups who did/didnt get the benefits,Implications,Antibiotics may be more helpful than I previously thought for hospitalized COPD
30、 patients Academic centers have been less inclined to use antibiotics in this setting I will be substantially more inclined to use them Recall last years report of importance of antibiotics for “chest infections”,The Ratty Renal Artery,Revascularization versus medical therapy for renal-artery stenos
31、is NEJM, November 2009 The ASTRAL investigators Funded by UK government and Medtronic,Purpose,Determine whether revascularizing atherosclerotic renal arteries improves outcomes, compared to medical therapy alone Background information Renal artery stenosis is associated with refractory hypertension
32、and CKD Revascularization, whether open or endovascular, is commonly performed Evidence of benefit is lacking Significant rates of serious complications,Method,Randomized clinical trial, unblinded 806 patients in the UK with “substantial” atherosclerotic RAS Found because of problematic hypertension
33、, unexplained kidney dysfunction Not “requiring” revascularization within 6 months, approachable by endovascular route, MD uncertain of benefit Received angioplasty +/- stent OR not All received locally determined medical therapies Followed 5 years for rate of decline in renal function, and multiple
34、 secondary outcomes,Results,Of 403 patients assigned to revascularization 335 attempted 317 successful, most with stent Of 403 assigned to medical therapy: 24 eventually revscularized Baseline GFR 40, SBP 150,More Results,No difference in GFR decline Both groups had very slow decline No difference i
35、n renal, cardiac, survival outcomes Frequent and severe complications of procedure 5% of patients Death, MI, renal failure, arterial perforation, systemic embolization, hemorrhage,Limitations,Unclear who was excluded Perhaps physicians are good at selecting who might or might not benefit from RAS co
36、rrection The rate of disease progression was much lower than expected,Implications,At least for a substantial subset of patients with RAS, revascularization Is dangerous Doesnt do any good Current medical therapy may be better than we imagine I wont be referring many patients for revascularization I
37、 wont be looking for RAS much, either,So Many Shots,Three-year efficacy of complex insulin regimens in type 2 diabetes RR Holman et al. NEJM. October 2009 Funded by insulin maker, which had a major role in study design and execution,Purpose,Determine whether different strategies of insulin administr
38、ation lead to different glycemic control Background Information Relatively few comparisons of type of insulin for diabetes Recall that ACCORD, ADVANCE, AND the VA trial all suggest that tight glycemic control is not helpful and may be dangerous,Method,Randomized clinical trial, unblinded 708 UK/Iris
39、h subjects with DM-2, A1C 7-10 On metformin and sulfonylurea, never insulin or TZD Started on one of: Daily detimir TID prandial aspart added if needed BID 70/30 biphasic Midday prandial aspart added if needed TID prandial aspart Daily detimir added if needed Followed 3 years for A1C, Hypoglycemia,
40、quality of life, many others,Results,Limitations,Most patients in all groups needed a second type of insulin Target A1C of 6.5 likely increased Insulin needs Hypoglycemia 15-25% dropout rate,Implications,Single daily long-acting insulin may be as good or better than other insulin strategies Similar
41、glycemic control Less hypoglycemia Less weight gain Possibly lower mortality? Glycemic control target remains unclear I will use a basal insulin approach This applies only to Type 2 diabetes,Another Look at the Colon?,Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a m
42、ulticentre randomised controlled trial WS Atkin et al The Lancet, May 2010 Funded by the UK government,Purpose,Establish whether a single flex sig can reduce colon cancer incidence and mortality Background information Colorectal cancer is common Annual or biennial fecal occult blood testing has been
43、 demonstrated to reduce colon cancer mortality Periodic colonoscopy, barium enema, flex sig and various combinations have been widely used for screening, but evidence of mortality benefit is lacking,Method,Randomized clinical trial, unblinded 170,432 UK residents Age 55-64 No prior colon cancer, rec
44、ent screening, other major illness, or strong family history Single flex sig Referred to colonoscopy if Large or multiple polyps Villous component Severe dysplasia or malignancy Followed 10-15 years for colorectal cancer incidence, and colorectal cancer death,Results,Half of invited subjects express
45、ed interest in screening 71% assigned to screening attended 5% of screened subjects referred for colonoscopy,More Results,Number screened to prevent 1 death = 489,Limitations,Amount of prior or subsequent screening in screened and control groups is unknown Only willing patients were invited 71% upta
46、ke of screening is likely higher than will be achieved in practice,Implications,First convincing evidence that endoscopic screening reduces colon cancer mortality Low risk and relative convenience of sigmoidoscopy are appealing Unknown if this is superior to FOB screening But it is one more good scr
47、eening option Just do something,Falls and Glasses,Effect on falls of providing single lens distance vision glasses to multifocal glasses wearers: VISIBLE randomised controlled trial MJ Haran et al. BMJ 2010 Funded by the Australian government,Purpose,Determine whether replacing multifocals with unif
48、ocal distance lenses, plus counselling regarding use outdoors, could reduce falls in high risk subjects Background Information Multifocal lenses impair foot placement Multifocal wearers have increased outside and on stairs,Method,Randomized clinical trial UNBLINDED! 606 Australians with multifocal g
49、lasses Age over 80, or Age over 60 plus additional fall risk Received new single-lens, distance glasses, plus counselling about hazards of multifocals and how to use unifocals OR nothing Followed 1 year for self-reported falls,Results All Subjects,Results Active Subjects,Number needed to prevent one injurious fall = 11,Limitations,Low activity subjects had increased falls with unifocal distance lenses Unclear exactly what is high and low outdoor activity Study not designed to distinguish whether the lenses, the counselling, or both were responsible for the effect,
