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

1. Boston Criteria (diagnosing heart failure) 

CRITERION	POINTS*
Category I: history
Rest dyspnea	4
Orthopnea	4
Paroxysmal nocturnal dyspnea	3
Dyspnea while walking on level area	2
Dyspnea while climbing	1
Category II: physical examination
Heart rate abnormality (1 point if 91-110 BPM, 2 points if >110 BPM)	1 or 2
Jugular venous elevation (2 points if >6 cm H2O; 3 points if >6 cm H2O plus hepatomegaly or edema)	2 or 3
Lung crackles (1 point if basilar; 2 points if more than basilar)	1 or 2
Wheezing	3
Third heart sound	3
Category III: chest radiography
Alveolar pulmonary edema	4
Interstitial pulmonary edema	3
Bilateral pleural effusion	3
Cardiothoracic ratio greater than 0.50	3
Upper zone flow redistribution	2

*— No more than 4 points are allowed from each of three categories; hence the composite score (the sum of the subtotal from each category) has a possible maximum of 12 points. The diagnosis of heart failure is classified as “definite” at a score of 8 to 12 points, “possible” at a score of 5 to 7 points, and “unlikely” at a score of 4 points or less.

2. Diagnosing COPD (physical exam): 

-One multicenter prospective trial (n=309) in {JAMA} found the following 4 physical exam findings to be diagnostic of obstructive airway disease in multivariate regression models:

-Smoking > 40 pack years (LR 8.3)

-Self reported history of COPD (LR 7.3)

-Maximum laryngeal height <4cm (LR 2.8)

-Age >=45 (LR 1.3) 

All 4 criteria = LR 220, 0 criteria = LR 0.13, ROC area = 0.86

3. Laryngeal height: 

4. Diagnosing COPD (spirometry):

-FEV1/FVC <5th percentile or <70% is diagnostic of COPD 

-FEV1

>80% of predicted: mild

50-80% of predicted: moderate (SOB with exertion)

30-50% of predicted: severe (worse SOB, frequent COPD exacerbations)

<30% of predicted: very severe (significant impairment in quality of life, COPD exacerbations are life-threatening. 

Since asthma responds to albuterol and COPD does not, If the FEV1/FEV improved by greater than 12%, it's more likely asthma than COPD 

-Asthma (eos, mast cells, Th2 helper T cells) vs COPD (m-phage, neutrophils, cytotoxic CD8+ t cells)

5. Quitting smoking & COPD:

{Am J Respir Crit Care Med, 2000} 

"Previous studies of lung function in relation to smoking cessation have not adequately quantified the long-term benefit of smoking cessation, nor established the predictive value of characteristics such as airway hyperresponsiveness. In a prospective randomized clinical trial at 10 North American medical centers, we studied 3,926 smokers with mild-to-moderate airway obstruction (3,818 with analyzable results; mean age at entry, 48.5 yr; 36% women) randomized to one of two smoking cessation groups or to a nonintervention group. We measured lung function annually for 5 yr. Participants who stopped smoking experienced an improvement in FEV1 in the year after quitting (an average of 47 ml or 2%). The subsequent rate of decline in FEV1 among sustained quitters was half the rate among continuing smokers, 31 ± 48 versus 62 ± 55 ml (mean ± SD), comparable to that of never-smokers. Predictors of change in lung function included responsiveness to beta-agonist, baseline FEV1, methacholine reactivity, age, sex, race, and baseline smoking rate. Respiratory symptoms were not predictive of changes in lung function. Smokers with airflow obstruction benefit from quitting despite previous heavy smoking, advanced age, poor baseline lung function, or airway hyper responsiveness." 

6. Treatment of COPD: 

Mild (FEV1 >80% of predicted) -- albuterol inhaler PRN 

Moderate (50-80% of predicted) -- inhaled anticholinergic (tiotropium, ipratropium) maintenance + albuterol inhaler PRN 

Severe (<50% of predicted) -- inhaled steroid + LABA maintenance + albuterol inhaler PRN. 

People who have very severe disease may require continuous oxygen or non-invasive vent support 

7. Vaccinations in people with COPD

-Flu shot (decrease COPD exacerbations by 50%)

-Pneumococcus (decrease incidence of CAP in people with an FEV1<40% predicted)

-Zoster (varicella can cause pneumonia) 

8. COPD exacerbations:

-Like asthma exacerbations/attacks, triggered most commonly by infections and pollutants. 

-Treat with albuterol or duoneb and PO steroids. 

9. Workup for suspected BPH:
-UA to r/o UTI
-BUN/Cr to check renal function
-PSA and prostate exam to check for prostate cancer
-Optional: urine flow rate (>15mL/sec effectively rules out clinically meaningful obstruction), bladder scan
-Optional: prostate symptom score
10. Management of BPH:
-Lifestyle modifications (drink less fluids before bed, less salt/sugar/spicy food, less diuretics including caffeine and alcohol, avoid alpha-agonists like decongestants and antihistamines)
-First line for those with small prostates (<40gms): alpha-antagonist like prazulosin
-For those with large prostates: add 5-a-reductase inhibitor like finasteride. These drugs can take up to a year to have effect
-Those who are experiencing clinically significant consequences of BPH need to get surgery- i.e. hydronephrosis, renal failure, recurrent infections, bladder decompensation (overstretch)

1. Suspected pneumonia in a child: 
-Only get a CXR if they are hypoxic or not responding to treatment
-Everyone who is admitted for bacterial pneumonia should get a PA and lateral CXR
2. Pneumonia in a child <1 month old: 
-Etiology: E.coli, GBS, listeria
-What to do: Admit
-How to treat: Amp and gent, amp and gent!!
3. Pneumonia in a child 1 month to 3 months old: 
-Etiology: S.pneumo, C.trachomatis, viruses (flu, paraflu, RSV, adeno)
-What to do: Admit if you suspect bacterial
-How to treat: Amp or Pen G or Ceftriaxone if you suspect resistance or kid is unimmunized.
4. Pneumonia in a child 3 months to 5 years old:
-Etiology: Atypicals first, then s.pneumo and viruses
-What to do: Admit if they are hypoxic (sat <90, RR>70), its a bad bug (MRSA) or you think the family won't follow up or won't take care of the problem.
-How to treat: Amoxicillin outpatient, Amp inpatient
5. Suspected bacterial pneumonia in a child >5 years old:
-Etiology: Atypicals, S.pneumo
-What to do: Manage as outpatient unless hypoxic or no family support
-How to treat: Azithromycin
6. Screening for metabolic in children (DM, hyperlipidemia, fatty liver) 
-Screen those with BMI > 85th percentile + risk factors
-Screen those with BMI >95th percentile
-Only start lipid lowering medications if diet and exercise have failed, LDL>190 or >160 + risk factors, and only start if they are older than 10 and are more than tanner stage 2 (male) or have completed menarche.
7. Worsening winter cough is suggestive of COPD-- the cold air causes constriction of airways, which worsens underlying lung disease.
8. Paroxysmal Nocturnal Dyspnea is much more closely associated with CHF than dyspnea on exertion (17% specificity).
9. COPD physical exam findings:
-Increased AP chest diameter
-Decreased diaphragmatic excursion
-End-expiratory wheezing
-Prolonged expiratory phase
10. CHF physical exam findings:
-JVD
-Lower extremity edema
-hepatojugular reflex
-S3
-laterally displaced and diffuse PMI
-pulmonary edema (crackles, dullness to percussion)

1. Diagnosing consolidation on lung exam:
-Egophony: patient says E sound, examiner hears A
-Tactile fremitus: examiner puts palms on b/l posterior rib cage, patients says "oi" sound (toy boat, or 99 in german). Increased vibration implies consolidation, decreased vibration implies effusion.
-Dullness to percussion: can imply consolidation or effusion or large mass
-Whispered pectoriloquy: when the patient whispers words, you hear them louder through the stethoscope on areas of consolidation or cavity.
-Crackles (high frequency, short duration)
-Rales (like crackles, but lower frequency and longer duration)
2. Diagnosing strep throat (Centor criteria) 
-Tonsillar exudates or erythema
-Anterior cervical lymphadenopathy
-Fever (>38 C/100.4 F)
-Absence of cough
-Age <15
One point for each of the above symptoms; subtract a point if they are aged over 44
-0 to 1 points: risk of strep throat <10% (ER) <5% clinic)
-2 to 3 points: risk of strep throat  15% for 2 criteria, 32% for 3 criteria; should do rapid strep test and treat with antibiotics if test is +. If it's negative, go to throat culture.
-4-5 points: Risk of strep throat 56%, empirical antibiotics.
3. Lower respiratory tract infections: Bronchiolitis
-Symptoms: begins as viral illness, progresses to wheezing, cough, dyspnea, cyanosis.
-Population: Peak incidence at 3-6 mos of age, rare in children over 2 years of age. 90% of hospitalizations for bronchiolitis occur in children <12 mos old.
-Common causal organism(s): RSV
-Treatment: neb racemic epinephrine PRN (better than scheduled), oxygen.
4. Lower respiratory tract infections: Bacterial Pneumonia 
-Symptoms: Usually no prodromal symptoms. In children, can present abruptly with fever and sputum. In adults, can present gradually with chest pain, fever, chills, dyspnea.
-Population: Very young, very old.
-Physical exam findings: Fever (>38), vital sign changes (RR, SpO2, HR), crackles, esp focal, pan-inspiratory crackles. Can also see focal wheezing, decreased lung sounds. 50% will have a accompanying pleural effusion.
-Common causal organism(s): S.pneumo
-Treatment: for kids, amox 90mg/kg/day divided into three doses per day for 7-10 days.
5. Lower respiratory tract infections: Viral Pneumonia 
-Symptoms: atypical respiratory symptoms (fever chills, dry cough) and a lot more systemic symptoms like myalgias, arthralgias, GI symptoms.
-Population: children aged 4 mos to 5 years.
-Common causal organism(s): In the winter, usually influenza, although can be caused by RSV in immunocompromised adults, measles/varicella in unimmunized people, and by "common cold" viruses like adenovirus, rhinovirus, parainfluenza. Common in children aged 4 mos to 5 years.
6. Lower respiratory tract infections: Atypical pneumonia
-Symptoms: classic pneumonia symptoms plus systemic symptoms-- GI disturbances (nausea, vomiting, diarrhea), myalgias, headaches, otalgia/otitis, pharyngitis.
-Population: young adults
-Common causal organisms: Mycoplasma, C.pneumonia
-Treatment: In children, azithromycin 10mg/kg/day on day 1, 5mg/kg/day on days 2-5.
7. Lower respiratory tract infections: Acute Bronchitis
-Etiology: viral infection of large airways leading to irritation, edema, obstruction with mucus and edema.
-Symptoms: URI symptoms + productive cough lasting longer than 5 days (with common cold, usually <5 days). 50% will have purulent mucus.
-Physical exam: wheezing, ronchi. Sometimes lung exam will be normal.
-Treatment: albuterol if there is wheezing.
8. Upper and lower respiratory tract infections: Influenza
-Symptoms: extremely abrupt onset of fevers (can go to 104), chills, myalgias, arthralgias, headache, weakness, followed by respiratory symptoms
-Population: everyone; worse in children. Affects 15-40% of school aged children; children under 2 generally have more complications and higher hospitalization rates.
-Exam: can hear ronchi, if the airways are inflamed.
-Prognosis: Fever, headache, sore throat usually last 3-5 days, but lethargy and cough can go on for weeks. Kids should stay out of school for 24 hours after the fever ends.
9. Antivirals for influenza:
-Decrease duration of illness by 24 hours only if given within first 48 hours.
-Only give after 48 hours if the person is clinically worsening at the exam, or if there are signs of a viral pneumonia (crackles, decreased sats/hypoxia sign, abnormal vitals). People who are particularly prone to influenza pneumonia-- kids with chronic lung disease like CF, asthma, BPD; people who are immunocompromised or immunosuppressed, adults with chronic diseases, people over 65.
10. Complications of infuenza:
-Bacterial superinfection with s.pneumo (most common-- staph is less common). 2-3% of kids with influenza will present with this, 14% of adults. T
-Progression to viral pneumonia
-Viral spread or bacterial superinfection to ears
-Rarely, neurological effects like guillain-barre, viral meningitis, febrile seizures (young kids)

1. SSRI for generalized anxiety disorder: paxil/paroxetine and lexapro/escitalopram are the only 2 SSRIs currently FDA approved for the treatment of GAD. (cymbalta/duloxetine and effexor/venlafaxine are SNRIs approved for GAD)
2. Effectiveness of Lexapro for GAD: 

{2004 RCT in Depression and Anxiety} investigated the efficacy of escitalopram (Lexapro) in the treatment of adults with generalized anxiety disorder (GAD). A total of 315 adults with GAD and Hamilton anxiety scores >=18 were randomized to receive escitalopram or placebo for 8 weeks. The escitalopram was given as 10mg/day for 4 weeks, then flexibly dosed 10-20mg/day for 4 weeks. Escitalopram statistically and clinically significantly improved Hamilton anxiety scores from week 1 to 8, with a mean change of -11.3 for escitalopram and -7.4 for placebo. Discontinuation due to adverse events was not significantly different between the two groups.

3. Effectiveness of Paxil for GAD:

{2003 RCT in Am J Psychiatry} investigated the efficacy of paroxetine (paxil) in the treatment of GAD in adults. A total of 566 patients aged 18-80 with GAD Hamilton anxiety score >=20 and no coexisting major depression were randomized to paroxetine 20mg vs paroxetine 40mg vs placebo once daily for 8 weeks. Response was defined as a rating of “very much improved” or “much improved” on the clinical global impression global improvement measure, and remission was defined as a Hamilton anxiety score <=7.

Response rates were 62% (NNT 7) and 68% (NNT 5) for paxil 20mg and 40mg respectively, vs 46% with placebo. Remission was achieved in 30% (NNT 10) and 36% (NNT 7) of those on paxil 20 and 40mg, vs 20% with placebo. Side effects were asthenia, somnolence, nausea, decreased libido, abnormal ejaculation.

4. Paxil vs Lexapro for GAD: 

{2006 RCT in Br J Psychiatry} compared the effectiveness of escitalopram and paroxetine in the treatment of adults with GAD; it also compared the effectiveness of differing doses of escitalopram. A total of 681 patients with GAD were randomized to placebo (n=139), escitalopram 5mg (n=134), 10mg (n=136), 20mg (n=133) and paroxetine 20mg (n=139). Mean change in Hamilton anxiety score was approximately 50% from baseline for all treatment groups. Specifically: for placebo the change was -14, escitalopram 5mg was -16, 10mg was  -17, 20mg -16, paroxetine -15. Escitalopram 10mg and 20mg were statistically significantly better than placebo and paxil.

The side effects that those taking taking paxil 20mg experienced that were statistically different from placebo were anorgasmia and insomnia. 

The side effects that those taking Lexapro 10mg experienced that were different than placebo: fatigue, insomnia, diarrhea, anorgasmia.

The side effects that those taking Lexapro 20mg experienced that were different from placebo were: fatigue, insomnia, diarrhea, sweating, somnolence, yawning.

5. Effectiveness of acupuncture for the management of low back pain: 

{2007 german RCT in Arch Intern Med} (multicenter) investigated the efficacy of acupuncture vs sham acupuncture vs conventional therapy in the treatment of chronic low back pain. A total of 1,162 adults with low back pain for mean 8 years were randomized to the aforementioned 3 categories. Acupuncture is the application of needles at “acupuncture points” specified by Chinese medicine. Sham acupuncture was the application of needles at nonacupuncture points, conventional therapy is a combination of drugs, physical therapy, and exercise. Both acupuncture and sham acupuncture were performed by trained practitioners of acupuncture. All interventions took place of 10-15 half hour sessions twice weekly. Response in terms of pain was defined as >33% improvement on Von Korff Chronic pain grade scale at 6 months, response in terms of function was defined as >12% improvement on hanover functional ability questionnaire at 6 months. Comparing acupuncture to sham acupuncture to conventional therapy, pain response was found in 59%, 51% and 34%, and functional response in 73% vs 65% vs 50%. There was no difference in outcomes between acupuncture and sham acupuncture, however both were significantly more effective than conventional therapy.

6. Effectiveness of acupuncture for management of chronic low back pain #2 (different group from above)

{2006 German RCT in Arch Intern Med} investigated the efficacy of acupuncture vs sham acupuncture vs no acupuncture. A total of 298 patients aged 40-75 with chronic low back pain were randomized to the three aforementioned groups, received 8 weeks of intervention (12 30-minute sessions) and were followed for 1 year. Both acupuncture and sham acupuncture were performed by trained practitioners of acupuncture Outcome was change in pain on a 100mm visual analog pain scale. There was no difference in pain outcome between acupuncture and sham acupuncture, however they were both associated with significant reduction in pain (~30mm) compared to placebo.

7. Topical tinea (cruris, magnum, pedis, corporis): topical antifungals are extremely effective in 2-4 weeks. Can use azole family (clotrimazole, micronazole, etc) or allylamine family (terbinafine = lamisil).
8. Types of skin biopsies:
-Incisional/punch: good for most cases, no need for stitches if <3mm in size.
-Excisional: with 2-3 mm margin, do it if you suspect malignant melanoma
-Shave: only for elevated lesions
9. Risk factors for recurrence/mets in cutaneous squamous cell carcinoma:
-Size >2cm
-Location on lip or ear
-History of radiation
-Immunosuppression
-Local recurrence
-Invasion depth >4mm
-Perineural or deep invasion
-Poor differentiation
10. Treatment for SCC:
-If its <2cm, no risk factors for malignancy, do wide local excision under local anesthesia. 4mm margins around visible lesion => 95% histologic cure rate.
-If its >2 cm, has risk factors for malignancy, has uneven edges or is in a cosmetically sensitive area, do Mohs surgery (remove tumor bit by bit, immediately check pathology-- good for uneven edges where you want to make sure you have margins)
-If patient refuses surgery, or it's impractical, or if its just actinic keratosis - topical 5-FU
-If patient refuses surgery, or it's impractical, and the tumor is small and non-invasive: cryotherapy or radiation. Only irradiate head & neck, not trunk or extremities-- poorer blood flow = greater risk of skin breakdown, poor healing.