1. FDA recommends AGAINST co-administration of clopidogrel (Plavix) and omeprazole
-Addition of omeprazole (CYP 2C19 inhibitor) reduces effectiveness of clopidogrel
-Separating doses does not reduce interaction
Additional recommendations
-Avoid using other potent CYP 2C19 inhibitors (including esomeprazole) with clopidogrel
-Insufficient evidence about drug interactions between clopidogrel and PPIs other than omeprazole and esomeprazole to advise on use
-Patients taking clopidogrel who continue to require such medication can use antacids and most H2 blockers such as ranitidine (Zantac), famotidine (Pepcid), nizatidine (Axid), but NOT cimetidine (Tagamet and Tagamet HB)
-On an unrelated note, warfarin is processed by cyp 2C9

2. National Lung Screening Trial: RCT published in the {NEJM} in 2011 investigated low dose CT vs CXR for detection of lung cancer and eventual mortality. Total N=53,454. Inclusion criteria: aged 55-74 years,  ≥ 30 pack year smoking history. Intervention: randomized to low-dose CT vs. chest x-ray screening and followed for a median of 6.5 years. A screening test was offered at baseline and 2 annual follow-up examinations (up to 3 tests total).

Outcomes: 

-Low dose CT caught 649 cancers, missed 44
-CXR caught 279 cancers, missed 137
-Incidence of lung cancers diagnosed per 100,000 person-years 645 (CT) vs. 572 (CXR) (p < 0.05)
-Lung cancer death in 356 patients (CT) vs. 443 deaths (CXR)
-Lung cancer mortality 1.33% (CT) vs. 1.66% (CXR) (p = 0.0004, number needed to screen [NNS]= 303)
-All-cause mortality 7.02% (CT) vs. 7.48% (CXR) (p = 0.02, NNS 218)
Trial begun 2002, and terminated 2010 due to loss of equipoise!

3. Post-hoc analysis of data from the above trial in 2013 in the {NEJM} to determine who should be screened for lung cancer. They stratified everyone from the above trial into quintiles for 5-year risk of lung cancer mortality based on age, body mass index, family history of lung cancer, pack-years of smoking, years since smoking, and emphysema diagnosis.

	Number needed to screen:	# false positives per prevented lung CA death	# lung CA deaths prevented per 10,000 person years
Quintile 1:	5276	1648	0.2
Quintile 2:	531	181	3.5
Quintile 3:	415	147	5.1
Quintile 4:	171	64	11
Quintile 5:	161	65	12

4. Lung cancer risk calculator based on above data, by the folks at Memorial-Sloan Kettering (http://nomograms.mskcc.org/Lung/Screening.aspx)

5. Is there a difference between the different PPIs in efficacy of treating GERD? A meta-analysis of 32 high-quality randomized comparison trials of different PPIs for GERD in {Aliment Pharmacol Ther} in 2003

Relief of GERD symptoms:

-At 1-3 days, 56% of lansoprazole vs 49% of omeprazole patients reported symptom relief (p < 0.0001, NNT 17) [1 trial] 

-At 4 days, similar efficacy between rabeprazole 20 and omeprazole 40 [1 trial]

-At 4 and 8 weeks, there was no difference in efficacy between pantoprazole 40, omeprazole 20 , and lansoprazole 30

-Omeprazole 20 = omeprazole 40 > Omeprazole 10 [2 trials] 

Maintenance of healing in GERD

-lansoprazole 15 = lansoprazole 30 mg = omeprazole 20 mg = rabeprazole 20 mg = rabeprazole 10 mg (low-dose) in trials lasting at least 6 months

6. Treating heartburn symptoms in endoscopy-negative GERD: This 2004 study examined 3 multi-center double blind RCT looking at esomeprazole vs omeprazole for resolution of heartburn symptoms in endoscopy-negative patients with GERD. Resolution defined as “no heartburn symptoms in the last 7 days” at 4 weeks.

-1,282 patients randomized to esomeprazole 40 vs. esomeprazole 20 vs. omeprazole 20 daily, 56.7% vs. 60.5% vs. 58.1% had heartburn resolution

-693 patients randomized to esomeprazole 40 mg vs. omeprazole 20 mg daily, 70.3% vs. 67.9% had heartburn resolution

-670 patients randomized to esomeprazole 20 mg vs. omeprazole 20 mg daily, 61.9% vs. 59.6% had heartburn resolution

Omeprazole is just as good as esomeprazole, 20 mg is probably enough.

7. In people with refractory GERD, is BID dosing more effective than qD? RCT in Japan (N=337) published in {Am J Gastroenterol} in 2012. Inclusion criteria: adults with reflux esophagitis in Japan refractory to once daily PPI for 8 weeks. Intervention: randomized rabeprazole 20 BID, rabeprazole 10 BID, rabeprazole 20 qD for 8 weeks

Heartburn symptoms resolved in:

-80% with 20 BID (p < 0.025 vs. 20 mg once daily)

-74% with 10 BID (p ≥ 0.025 vs. 20 mg once daily)

-56.4% with 20 qD

Endoscopically confirmed healing in

-77% with 20 BID (p = 0.003 vs. 20 mg once daily)

-78.4% with 10 BID (p = 0.001 vs. 20 mg once daily)

-58.8% with 20 qD

Conclusion: 10 BID of rabeprazole = 20 BID rabeprazole > 20 qD

(Extrapolating loosely from above studies, if rabeprazole 20 is roughly equivalent to omeprazole 40, then perhaps taking omeprazole 20 BID will work better than omeprazole 10 BID. Omeprazole 20 BID may or may not be better than omeprazole 10 BID)

8. Joint injections of prednisone may be effective in treating gout that affects large joints. Triamcinolone was studied in 1 trial (n=19), 100% of the participants reported significant pain relief at 48 hours.
9. About smoking cessation: 
-Oral medications are somewhat effective (12-month quit rates 1.5–3x placebo)

-Most smokers quit multiple times before final success.
-View tobacco abuse as a chronic disease and continue to work with smokers who relapse.
-Annual quit rate for smokers with no medical interventions is 2–3% per year.
-Quit rates are highest when patients are engaged in a group setting.
-When combined with medication, one-on-one counseling sessions (as in a physician’s office), enhances quit rates.
-Studies have shown that providing practical problem-solving skills, assistance with social supports, and use of relaxation/breathing techniques can increase quit rates.
10. When a patient is ready to quit smoking:
-Set a quit date.
-Have patient call 1-800-QUIT-NOW or go to www.smokefree.gov
-Instruct patient to start taking bupropion one week before the quit date:
-Start with one pill a day for the first three days, then increase to one pill twice a day, morning and evening. After another four days, stop smoking and continue on the pills twice a day. 

-May add nicotine gum for bad cravings, if needed. 

-After about two months on the pills, gradually stop