GIM-The Year in Review 2010 (and early 2011) How to make this talk. Topics! 6/21/2011

Transcription

1 GIM-The Year in Review 2010 (and early 2011) No conflict of interest How to make this talk. Areas Searched Based on cases from our clinic Medline ACP Journal Club Residency Journal Clubs Practical, Applicable, Interesting Whatever is not being covered elsewhere. Topics! 1- Supplement with an unforeseen effect 2- primum non nocere (1 st no harm) 3- Technology in search of an indication 4- Shots in the arm 5- Nuts! Which of the following interventions was NOT amongst the AHRQ recommendations for treatment of osteopenia? A. Weight bearing exercise B. Vitamin D 800-2,000iu qd C. Alendronate weekly D. Calcium 1,200 mg daily E. Smoking cessation 71% 2% 4% 8% 16% A. B. C. D. E. 1

2 Case #1- Supplemental Calcium- an unforeseen effect A 65 year old woman with no significant problems except for hypertension which she controls with the DASH diet presents for her routine visit. Her screening DEXA scan shows mild osteopenia. She feels well, how should you manage her? AHRQ-National Guidelines for Osteopenia treatment Core Principles of Treatment Dietary calcium 1200 mg/d and 800 to 1000 international units (IU) vitamin D 3 [B] Weight-bearing exercise [A] Address modifiable risk factors Smoking, excess ETOH, corticosteroids, eating disorders Vitamin D and fracture data Meta-analysis: 5 RCTs for hip fracture (n = 9294) 26% RRR 7 RCTs for non-vertebral fracture risk (n = 9820) 23% RRR iu/daily cholecalciferol (1,25 vitamin D) Bischoff-Ferrari et al. JAMA. 2005;293: Vitamin D- All Cause Mortality Meta-analysis- 18 RCT s, 57K patients Mostly elderly BUT 30% from WHI Arch Intern Med. 2007;167(16): % Summary Risk Reduction for Death- ALL CAUSE!! 2

3 Calcium Supplements Benefits: Modest bone effects Well tolerated Up to 50% population take supplements QJM (2010) 103 (2): 125 Calcium Supplements Benefits: Modest bone effects Well tolerated Up to 50% population take supplements Concerns: Accelerate vasc. calcification in HD 2 RCT s with 20% increased MI in healthy older women QJM (2010) 103 (2): 125 Am J. Med 2006;119:777 BMJ 2008;336:262 Calcium/Vit D and CV risk meta #1 Conclusions: Limited data available Pt level Meta #2 Cumulative incidence of cardiovascular events- Calcium vs. Placebo Vitamin D 10% reduction ( ) Calcium 14% increase ( ) Calcium + Vit D 1.04 (unity) Lu Wang, Annals of In. Med. March 2, 2010 vol. 152 no trials: >100 subjects >500mg Ca++ 12,000 participants 1000 people for 5 years 14 MI s, 10 strokes, prevent 26 fractures 31% 20% 18% Bolland M J et al. BMJ 2010;341:bmj.c3691 3

4 Does this prove Calcium effect? Biologic plausibility? Hyper PTH increased CV mortality Bolus effect of supplement PTH increase Platelet stickiness via CA receptors Vascular smooth muscle effects At odds with the Women s Health Initiative 36K patient trial over 7 years 1G Calcium, 400iu Vitamin D = no CV effect Vitamin D may be protective Meta #3- Calcium/Vit D with WHI data Patient level Meta-analysis 25K patients (most WHI) (54% WHI patients on Calcium at enrollment) NNH for 5 years 178 cause a MI or stroke NNT for 5 years 302/prevent Fx Vitamin D not protective of calcium negative effect BMJ Apr 19;342:d2040. doi: /bmj.d % 15% P= % Dairy Vegetables Fish Fortified Foods Table 1. Dietary Sources of Calcium FOOD Cheese (Cheddar) Cottage cheese Cream cheese Milk Sour cream, reduced fat Yogurt Bok choy, raw Broccoli, fresh, cooked Cabbage, fresh, cooked Collards, fresh, cooked Soybeans, cooked Spinach, cooked Turnip greens Salmon, canned Sardines, in oil Bread, whole wheat/white Breakfast bars Fruit juice, calciumfortified Instant breakfast drink SERVING SIZE 1 oz. 4 oz. 2 Tbsp 2 Tbsp 4 oz. 3 oz. 3 oz. 1 slice 1 bar CALCIUM PER SERVING (mg) Calcium Bottom Line Supplemental Calcium increases risk (dose relationship not proven) Osteopenia Treatment Vitamin D supplementation (800-2K iu) Push dietary calcium NO increased risk AHRQ Guidelines w/o Calcium supplement Osteoporosis Rx: no change with Ca/Vit D and bisphosphonate 4

5 Case #2-primum non nocere 69 year old man is in your clinic. You treat his diabetes and hypertension successfully and he is on a statin for elevated LDL cholesterol. He suffers from painful osteoarthritis of his knees. He has not taken any medications for this and asks your advice. Framingham 10 year risk score is 29%. He has no history of upper GI bleeding. You would recommend? A. Trial of Ibuprofen B. Advise Tai Chi or water aerobics program C. Trial of topical diclofenac gel or acetaminophen D. A and B 2% E. B and C 6% 10% 4% 78% A. B. C. D. E. OA-Current Guidelines Osteoarthritis (OA) is highly prevalent, affecting > 50% of people aged > 65 years AGS Recs for high risk CV patients APAP, exercise, short term/topical nsaids, opiates Osteoarthritis and Cartilage Volume 19, Issue 4, April 2010 JAGS 2009, Volume 57, Issue 8 Systematic Review topical NSAIDS Diclofenac 1.5% bid Equally efficacious, peak levels 1/150 th Increased local reactions Postgrad Med Nov;122(6): Guideline: Avoid oral NSAIDs in high risk patients who is high risk? Risk of Death in Denmark after first MI post discharge N=58,432 (36%NSAIDS) Risk of Death in Denmark after first MI post discharge N=58,432 (36%NSAIDS) NNH=13 NNH=14 NNH=45 NNH=24 NNH=123 Gislason, G. H. et al. Circulation 2006;113: Gislason, G. H. et al. Circulation 2006;113:

6 Biologic Plausibility?? Biologic Plausibility?? Endothelial effects: Inhibits prostacyclin Endothelial effects: Reduced prostacyclin Vasoconstriction Decreased Plt inhibition Vasoconstriction Decreased Plt inhibition Unopposed COX-1 Platelet aggregation Biologic Plausibility?? Thrombotic Badness Implication of the relative degrees of selectivity Endothelial effects: Reduced prostacyclin Vasoconstriction Decreased Plt inhibition Pain control roughly equivalent Unopposed COX-1 Platelet aggregation 6

7 Network Meta-analysis NSAIDs and CV Outcomes- who is high risk? Network Meta-analysis -Increases power over other meta-analysis - Enables direct and indirect comparisons CV Outcomes by NSAID Type 31 trials -Large RCT s -NSAID vs. NSAID vs. Placebo -116K patients -115K patient years -29/31 trials high quality -Cancer pts excluded -Reported all RR s >1.3 (noninferiority margin in MEDAL trial) Two Goals of the study 1- Magnitude of risk with each agent 2- Is risk limited to high risk patients Trelle S et al. BMJ 2011;342:bmj.c7086 Results -Everything to the right of unity -Little reaches significance; pts young, healthy, rare outcomes APTC Composite (MI, CVA, CV Death) -Elevated for all -IBUPROFEN highest! RR=2.26 Trelle S et al. BMJ 2011;342:bmj.c7086 Bottom Line NSAIDs None appear completely safe from CV standpoint Not clear that Ibuprofen is safer than COX-2 agents (more stroke, less MI?) Naprosyn appears safest Need to evaluate not only GI safety but CV safety before long term use Effect seems to be dose and time sensitive Follow step care guidelines for OA Technology in search of an indication Case #3 A healthy 55 year old female executive without angina completed a normal modified Bruce protocol exercise test. She also had a cardiac CT scan at work which showed several calcifications of her coronary arteries. What should you do? A. Send patient for cardiac catheterization B. Repeat the patients exercise test C. Echo and Cardiac Bypass if has low LVEF D. Risk factor management E. None of the above s/ct.jpg 15% 0% 0% 0% 85% A. B. C. D. E. 7

8 Cardiac CT CAD common 400K deaths annually Angiography-- Gold standard test Risks= small mortality risk, dissection, arrythmia Non-invasive testing important Cardiac CT- new 64+ slice scanners Noninvasive, improved image quality Prevalent: 23% >50% of practices own equipment Radiation, dye Diagnostic Accuracy is debated! Cardiac CT scan Government sponsored meta-analysis Institute of clinical and economic review 42 accuracy studies, 11 outcome studies Ollendorf J Gen Intern Med Mar;26(3): Epub 2010 Nov 10 Cardiac CT- the perfect test? Spectrum Bias Majority of data from high risk patients so test characteristics set from sick population NO data from low pretest probability patients Decreases accuracy Limitations Long term outcomes Radiation outcomes Incidentalomas PPV=50-60% Ollendorf et al. J Gen Intern Med Mar;26(3): Redberg. J Gen Intern Med Mar;26(3): Bottom Line Cardiac CT Very good sensitivity and specificity In high risk patients Promising in small number of ER studies with good negative predictive value (but? better than other tests available here) Lack data for Low Risk patients Case patient- risk modification (Personally low threshold for statin and lifestyle modification) 8

9 New Guidelines issued This public health intervention reduces mortality by 50% in patients over the age of 65 years old. A. Adding a statin for secondary prevention B. Wearing bike helmets C. Safe sex campaigns D. Hypertension control E. Annual Influenza Shots 10% 4% 0% 16% 70% A. B. C. D. E. Effectiveness of Influenza Vaccination Group and Variable People > 65 Years old Hospitalization for acute and chronic respiratory illness % Reduction 32% Hospitalization for pneumonia and influenza 39% Hospitalization for congestive heart failure 27% Deaths from all causes 50% Nichol et al. N Engl J Med Oct 4;357(14): Vaccination Schedule N Engl J Med Mar 22;344(12): Advisory Committee on Immunization Practices (ACIP) new schedule CDC generally follows their advice Schedule link: ontent/154/3/,danainf o= 68.full Ann Intern Med Feb 1;154(3):

10 Some Highlights 1- Everyone > 6 months old get flu vaccination 2- Tdap for adults close to infants (all ages x1, especially postpartum parents, healthcare workers) 3- HSV single shot at 60- regardless of serostatus 4- HPV4 or 2 for all year olds- catch up until HPV4 may be given for boys/men ages 9-26 to prevent warts HPV Vaccine 2 Vaccines with proven safety/efficacy Gardisil (quadrivalent) HPV 6, 11, 16, 18 Cervarix (Bivalent) 16, 18 Vaccine does not have DNA or attenuated virus! 3 doses (0, 2, 6 mos) $360 for series At least 5 years protection Quadrivalent (6,11,16,18) HPV Data- FUTURE II Study RCT, 12,167 women years old 3 doses vaccine, 4 years follow-up Vac Placebo RRR NNT All Lesions 1.4% 2.4% 44% 94 CIN 2 0.7% 1.6% 57% 111 CIN 3 0.9% 0.9% 45% 130 In Situ 0.08% 0.1% 29% NS! NEJM 2007;356: HPV4 in Boys/Young Men 4065 healthy boys and men 16 to 26 years of age, from 18 countries. Mean 30 month f/u HPV Placebo ITT- 36 lesions- RRR 60% Per Protocol- 90% ITT- 89 lesions 1- NO long term follow up for efficacy, cancer outcomes, herd protection 2- Cost effectiveness questions N Engl J Med 2011; 364:

11 Antivaccinationistas Lancet Feb. 28, 1998 published a case series of 12 children with regressive autism and colitis after MMR vaccination Retracted Feb. 2, 2010 after discovered it was totally falsified Andrew Wakefield MD loses license- unethical behavior Paid $435K by a lawyer before starting research 199/FU133 Dietary Update 44 year old healthy woman comes to your office asking how to add healthy protein to her diet as she is on a low calorie western diet but feels tired at the end of the day. She has mild hyperlipidemia. Consuming which of the following would help her lipid profile and to be a source of protein? A. Two handfuls of nuts twice daily B. Diet Soda between meals C. Energy bars twice daily D. Green tea for hydration E. Dark Chocolate 6 grams daily 93% 0% 0% 2% 5% A. B. C. D. E. NUTS!! Estimated effects of nut consumption on blood lipid and lipoprotein levels by percentage of dietary energy from nuts GISSI trial showed: -CHD risk was 37% lower in those who ate 4 servings of nuts/week -almonds, peanuts, pecans, pistachios, walnuts % unsaturated fats, 10-25% protein - antioxidants, improve endothelial fxn, GISSI Lancet 1999:354: Shows Dose response 7.4% overall reduction of LDL Sabate, J. et al. Arch Intern Med 2010;170:

12 Go NUTS!! Eat 3-4 handfuls of nuts daily 2 Oz of Dark Chocolate daily 2 Cups of green tea daily Walk or bike to work Red meat or processed meat in moderation Probably add up to close to a statin 2010 (and early 2011) The Year in Review Thank you for your attention! 12