BCPS 2013: Cardiology I

A little in the past on my study schedule, but what I'm studying this past week. Acute Decompensated Heart Failure

Parameter	Normal	ADHF
MAP	80-100	60-80
HR	60-80	70-90
CO/CI	4-7 / 2.8-3.6	2-4 / 1.3-2	Low cardiac output
PCWP	8-12	18-30	Congestion
SVR	800-1200	1500-3000
CVP	2-6	6-15	Fluid up

*want PCWP 15-18 for optimal filling pressure

Signs and symptoms

Congestion (PCWP)	Hypoperfusion (CO)
Dyspnea	Fatigue
Peripheral edema	Cold extremities
Rales	Narrow pulse pressure
Ascites	Hypotension
Jugular venous distention	Worsening renal function
Hepatomegaly, splenomegaly	Hyponatremia

Subsets and Therapy

	Warm (CI > 2.2)	Cold (CI < 2.2)
Wet (PCWP > 18)	Congestion IV diuretics + IV vasodiliators (venous)	Congestion and Hypoperfusion
		MAP < 50	Dopamine
		MAP > 50	Inotrope* or vasodilator (V or A)
Dry (PCWP < 18)	Normal Optimize oral meds	Hypoperfusion
		PCWP < 15		IV fluids
		PCWP > 15, MAP < 50		Dopamine
		PCWP > 15, Map > 50		Inotrope* or vasodilator (arterial)

*SBP < 90, hypotension, worsening renal function

Home HF meds in ADHF

• ACEi – caution with uptitration during diuresis and if Scr # more than 0.5 mg/dL above baseline
• BBlockers – Do not discontinue if stable prior to admission, do not start until euvolemic, hold if hemodynamically unstable
• Digoxin – goal conc 0.5-0.8 ng/mL, avoid discontinuation, caution if renal function worsens

Drugs for ADHF

Diuretics – congestion

Loop	Furosemide 40 PO = Furosemide 20 IV = Bumetanide 1 mg = Torsemide 10 mg
Thiazide	Not effective if CrCl < 30, used as adjunct HCTZ 12.5-25 mg PO, metolazone 2.5-5 mg PO Chlorothiazide 250-500 mg IV if GI edema (expensive)
Resistance to diuretics	Fluid and sodium restriction Increase dose, frequency, cont infusion Add thiazide

Inotropes – hypoperfusion

Dobutamine B1 agonist: inotropic, lusitropic, chronotropic	Dose: 2.5-20 mcg/kg/min AE: tachycardia, arrhythmia, myocardial ischemia Consider if hypotension
Milrinone PDE inhibitor: inotropic, lusitropic	AE: arrhythmia, hypotension Dose: 0.1-0.75 mcg/kg/min Consider if on B-blocker

Vasodilators – congestion, (Venous $ PCWP for dyspnea), (Arterial  $ SVR for $ CO)

Nitroprusside Arterial = venous	Doses: 0.3-3 mcg/kg/min AE: hypotension, cyanide/thiocyanate toxicity
Nesiritide # Na excretion, UOP, CI $ PCWP, SVR, NE, aldosterone	Doses: 0.01 mcg/kg/min AE: hypotension, some tachycardia
Nitroglycerine Venous > arterial (art w/ high doses)	Doses: 5-200 mcg/min AE: hypotension, reflex tachycardia, HA

Arrhythmias

Drug therapy overview

• Check thyroid function, K 4-5 mmol/L, Mg > 2 mg/dL, QTc < 500 ms
• Potential drug causes: QTc prolongation, bradycardia, AV block

See figures on last page.

See Table 9.

Treatment of arrhythmias

Pulseless VT/VF	Epinephrine, Vasopressin, Amiodarone, Lidocaine, eval reversible causes
PEA	Epinephrine, Vasopressin, eval reversible causes
Sx Bradyarrhythmia	If unstable: atropine 0.5-1.0 mg IV, repeat up to 3.0 mg
Sx Tachycardia	If unstable: cardioversion If stable: narrow/regular (SVT) – Vagal maneuvers, adenosine, β blockers, CCB, ablation Note: avoid CCB and digoxin if WPW, adenosine 6/12 mg (caution in severe CAD)
Afib (narrow/irregular)	Control ventricular rate (β blockers, CCB (diltiazem, verapamil), digoxin) Rate (leave in AF) OR rhythm control (restore sinus rhythm) Rate control with drugs listed above Rhythm control with electric cardioversion or antiarrhythmic drugs IA (quinidine, procainamide), IC (flecainide, propofenone), III (amiodarone, sotalol, ibutalide, dofetilide) Anticoagulation Rate control: chronic anticoagulation ASA or warfarin (INR goal 2-3) (CHADS2 score) Rhythm depends on timing < 48 hrs AF, no anticoagulation needed  prior to cardioversion > 48 hrs AF, anticoagulation for 3 wks prior and 4 wks after CV Consider long term antiarrhythmics if pt still symptomatic despite rate control
Vtach, Vfib	Cardiovert (shock) patients, give Epi or vasopressin as needed Consider amiodarone or lidocaine during CV and after for prophy Patients with LVEF < 30 to 40% should have implantable cardioverter defibrillator (ICD)
Torsades	Mg
Special populations	HF – amiodarone and dofetilide (LV dysfxn post MI) neutral effect on mortality Post MI – ecainide, flecainide, moricizine, 1A meds # mortality Dofetilide neutral mortality LV dysfxn post MI

Pulmonary Arterial Hypertension

Signs and symptoms

Dyspnea w/ exertion, fatigue, chest pain, syncope, weakness, orthopnea, peripheral edema (fluid backs up), liver congestion, ascites, hemodynamics (mPAP > 25, PCWP < 15, PVR > 3), RV hypertrophy

Treatment

Goal: relieve acute dyspnea, improve exercise capacity and QOL

Vasodilator response testing: epoprostenol, inhaled nitric oxide, IV adenosine

Initial treatment algorithm

Supportive care
Oxygen
Anticoagulation: warfarin goal INR 1.5-2.5 to prevent catheter thrombosis, VTE
Immunizations
Birth control
Oral CCB
If no sustained response to CCB:
Low risk	High risk
1st line: ERA or PDEIs (oral) Alt: epoprostenol, treprostinil (IV) iloprost (inhaled), treprostinil (SC)	1st line: epoprostenol, treprostinil (IV) Alt: ERA or PDEIs (oral) iloprost (inhaled), treprostinil (SC)

ERA: endothelin receptor antagonist (e.g. sentans)                      PDEIs (e.g. sildenafil)

Prostacyclin analogs (e.g. epoprostenol)

See Table 16.

Hypertensive Crises (Urgency and Emergency)

HTN urgency: acute elevation in BP > 180/120 without organ damage

HTN emergency: HTN with organ damage (encephalopathy, intracranial hemorrhage, angina or MI, pulm edema, aortic dissection, retinopathy, $ UOP or AKI, eclampsia)

Treatment

Urgency: goal to $ BP within 24 hrs

Agents (Table 18): captopril, clonidine, minoxidil, nifedipine, labetalol

Emergency: goal to $ MAP 25% or diastolic BP to 100-110 mmHg within 30-60 min

Agents (Table 17): sodium nitroprusside, esmolol, labetalol, nicardipine, nitroglycerin, hydralazine, enalaprilat, fenoldopam, clevidipine

Preferred agents for crises based on comorbidities

Acute aortic dissection	Esmolol alone or w/ nicardipine or nitroprusside (BB first!)
Acute HF	Nitroprusside, nitroglycerin, nesiritide, ACEi with diuretics if pulm edema (no BBs)
Stroke (ischemic, hemorrhagic)	Labetalol, nicardipine
Acute MI	BB with nitro, if HR < 70 nicardipine, clevidipine
Acute pulm edema	Nesiritide, nitroglycerin, nitroprusside
AKI	Fenoldopam, nicardipine, clevidipine
Eclampsia	Hydralazine, labetalol, nicardipine
HTN encephalopathy	Nitroprusside, labetalol, fenoldopam, nicardipine
Perioperative HTN	Clevidipine, esmolo, nicardipine, nitro
Sympathetic crisis	Nicardipine and such (avoid unopposed BB)

Cardiac Muscle

BCPS 2013: Statistics

This is a collection of reviews that I have found across the web to help you on your journey of obtaining the BCPS certification (along with me, of course).  I don't know about you but statistics as a class was not my favorite.  In fact, I believe that I am not cut out for the left-brained thinking that statistics require.  HOWEVER, I feel that I had a MAJOR grasp on the statistics portion of the test in 2012 and yes...  statistics is on there in a big way.  (Don't let anyone kid you though, don't forget regulations and pharmacoeconomics like I did). This is a slide handout from Tony Gerlach, PharmD, BCPS

Dr. Ted Williams has a study guide here.

So first, you want to know the type of data you are dealing with.  How much (quantitative) vs. what type (categorical) data?

Quantitative variables can be continuous or discrete. Continuous variables, such as weight, can in theory take any value within a given range. Examples of discrete variables are: number of kids in a family, number of attacks of COPD per year.

Categorical variables are either nominal (unordered) or ordinal (ordered). Examples of nominal variables are male/female, alive/dead, blood type O, A, B, etc.

The key for nominal variables with more than two categories is that the order does not matter. For example, one cannot say that people in blood type A lie between those in A and O. Sometimes, however, people can provide ordered responses, such as grade of colon cancer.  In this case the order does matter and it is usually important to account for it.

You could turn blood pressure measurements into nominal data by listing hypotension, normotensive, or hypertensive.  Height (continuous) could be changed by short, average, or tall.  Get it?

By this point you should understand what MEDIAN, MEAN, and MODE.

Mean is the average of all.

Median is the middle point in relation to mean points.

Mode is the most common data point.

Let's go deeper.

The mean is what we all know.  The average.  It is affected by changing data points.  A major disadvantage of the mean is that it is sensitive to outlying points.

The median is known as a measure of location; it tells us where the data are.   The value of the median isn't changed by making the smallest data point smaller and largest point larger.  It is LESS efficient in that it does not include all the information of the data.  JUST the middle point.

The range is an important measurement because it tells you the top and bottom of the data points.  However, they do not give much indication of the spread of observations about the mean. This is where the standard deviation (SD) comes in.

More later...

Have some better info?  Have some better links on learning stats?  Comment here!

More Medical Biostatistics: Who Doesn't Love It?

A coworker called me a numbers person yesterday.  This was shocking because I am not (I don't think)...  but, if you are going to take on the BCPS certification, statistics will be about 25% of the test (or so they say).  Guess what?  After studying and learning stats as it pertains to my field (medical studies and pharmacy) I can say that I may be a lover of stats now.  This statement would not have been uttered much less thought in April 2012 when I started this journey.

Background and the Endpoint:

• We can’t study every single person.  We draw conclusions or make inferences to the data so that we can determine if we are going to accept or reject the null hypothesis.  There is no difference between the two groups (null hypothesis).

Mean:

1. Known as the arithmetic mean - parametric, continuous data
2. Caution with outliers; may need to present data as median

Median:

1. Middle most value (or) 50th percentile value
2. Usually used with ordinal data or continuous data not normally distributed (outliers that skewed the data)

Mode:

1. Most frequently occurring number

Graphically:

Mean = Median = Mode (roughly equal)

Range = Interval between the lowest and highest value

Interquartile Range = 25th - 75th percentiles and related to the median

Standard Deviation (+/- SD):

• SD = square root of variance
• Estimates degree of scatter of sample data points about hte sample mean; only applicable to parametric data

Standard Error of the Mean (SEM):

• SEM = SD/square root of n (sample size)
• Average variability within a sampling distribution (if study repeated?)
• Caution in its use and interpretation; smaller than SD

Confidence Interval:  95% confident that the data falls in this area (want tighter) -- make this tighter by increasing the sample size.

Types of Data Scales:

1. Continuous - (Parametric) - follow assumption that the median = mode = mean (follow normal distribution (Common statistical tests: T-test, ANOVA)
2. Nonparametric - Nominal data, Ordinal data, continuous data (not meeting certain assumptions) (Common stat tests:  Mann-Whitney U, Wilcoxan Rank Sum, Sign Test)

Positively Skewed Data - Skewed to Right (refers to most data points to the left and the tail to the right)  (Mean > Median > Mode)

Negatively Skewed Data - Skewed to the Left (refers to most data points to the right and the tail to the left)  (Mean < Median < Mode)

Nominal Data:

• Categorial variables that have no sense of “ranking”
• Only get a mode and frequency
• No measure of variability to describe this type of data (i.e., standard error of the mean, SEM; or standard, SD)
• Numbers are arbitrarily assigned to characteristics for data collection
• Examples:  Gender (yes or no), Mortality (yes or no), Continuous data can also presented as a nominal endpoint so be careful how it is asked.  “How many people achieved SBP of < 140” -- trick question of using a continuous data type as NOMINAL by the way the question was asked (meeting a SBP goal or cut-off).

Ordinal Data:

• Can generate a mode, median, and frequency
• Still cannot use SEM and SD
• Measure of variability:  Range, interquartile range
• Numbers used to indicate rank-order, but do not have the same magnitude of difference between them
• Examples:  NYHA FC for heart failure, Pain scale, Glasgow Coma Scale
• Examples of trickery:  Blood pressures into groups - 100-120, 120-150, 150-190 treating the continuous points as ordinal data

Continuous Data:

• Can get a mode, median and mean
• Measure of variability - standard deviation and range, interquartile range
• Interval Data - Units of equal magnitude, rank order but is without an absolute zero (temperature)
• Ratio Data - Same as interval, but there is absolute zero (e.g., pulse or blood pressure)

Independent Groups:

• Not the same pts in each group (i.e., they are different people, though they may be matched based on certain characteristics)

Dependent Groups:

• Groups being studied are not different
• Examples: patient in a cross-over study, identical twins, right eye vs left in the same pt

Fisher’s Exact is used in SMALL sample sizes (<30-40) over Chi-square (Nominal, two independent sample tests)

Mann Whitney U for continuous when the continuous data doesn’t meet the assumptions of being parametric or follow normal distribution.  (i.e., outlier)

Hypothesis Testing - Power Analysis

• Power = 1 - Beta
  • Indicates the probability that a statistical test can detect a significant difference when it in fact it truly exists
  • Since Beta indicates the probability of making a type II error, the power calculation tells you the probability that you will NOT make a type II error.
  • If you reject the null hypothesis, low power not enough patients?

alpha = 0.5 - 5% chance that the results that you find are not right.  The smaller your alpha the least likely to make a Type I Error.

Power Analysis - Accept or Reject Null Hypothesis Decision -- Reality Null False or True

Factors that determine or impact the Power of a study:

• Alpha value (alpha)    
• Sample size (n)
• Types of groups evaluated in the study
• Type of alternative hypothesis selected
• Choice of statistical test used

Components needed for power calculation:

• Sample size (n)
• Standard deviation
• Practical significance (Delta)
• Z alpha (1-sided is 1.65 and 2-sided is 1.96)
• Z beta (based on level of power chosen)

Alpha (alpha) Value

• Should be determined a-priori (prior to test)
• Defined as the max acceptable probability of making a type I error
• Most will not select alpha > 0.05 or 5% or < +/- 2 SD from the mean
• The alpha and sample size have greatest impact on the power of a study

P-Values

• WILL NOT tell you the degree of clinical significance
• It helps to determine the likelihood that a difference seen is due to chance or random error
• A p<0.0001 is NOT more “clinically significant” than a p<0.001
• P=0.01 means that there is a 1% chance that the results you found in your statistical analysis are either due to chance or random error.
  • The smaller the p-value the more likely the results you found are real; that is why a researcher wants small p-values!!!

95% Confidence Interval

• What does it really tell you?
• This depends on the SEM and the degree of confidence we choose (95% vs. 99% CI)
  • 2 +/- SD is 95% of data; 3 +/- D is 99%
  • To calculate a CI you need the: mean, SD, sample size (n) and Z-score (which is 1.96 for 95% CI and 2.58 for 99% CI)

• The closer a point lies to the middle of the 95% CI the more likely it will reperesent the true population
• The CI can be made to be more narrow or precise with an increase in sample size (n)
• Interpreting the significance in a given CI
  • 95% CI be rejected for Odds Ratio or Relative RIsk if it contains “1.0”

We are trying to avoid making a:

Type I Error (the results say there is a difference but in reality there is no difference)

Type II Error (the results say there is no difference but in reality there is a difference)

Relative and Absolute Risk and Odds Assessment

Relative Risk (RR):  the risk of the event after the experimental treatment as a percentage of the original risk

RR = incidence rate in exposed patients / incidence rate in non-exposed patients

RR = 1 (incidence is the same for both groups)

RR = >1 (incidence in exposed group is higher)

RR = <1 (incidence in exposed group is less)

RR = 0.33/0.24

     = 1.375

Nominal data - Chi Square

ERR = 37.5% excess risk in causing edema

RR > 1 excess risk of something to the exposed group - in this case the CCB causes edema

“37.5% excess risk in causing edema”

RRR - Relative Risk Reduction when the RR is < 1

RR=0.0126/0.0217

    =0.581

RRR = 1-0.581 = 0.419 = 41% of risk for an MI was decreased from use of ASA

Nominal data - Chi square

Absolute Risk Reduction

ARR = RR control - RR treatment

=(248/3,293) - (147/3,275)

=0.0226 or 2.26

NNT = 1/ARR

=1/0.0226 = 44 pts

So I would have to treat 44 pts for 4.9 years to prevent 1 MI or death from CHD

Sample RR Interpretation:

The effect of ASA on vascular death relative to no aspirin was a RR of 0.8 and the RRR was 20%.  How should we interpret that?

The risk of vascular death in the aspirin group at 5 weeks is 80% of the risk in the control group, therefore ASA reduced the risk of vascular death by 20%

Odds Ratio

Estimates the RR in retrospective studies, since the # of pts at risk is not known, preventing the calculation of incidence.

Use of OR in prospective study will overestimate the risk!

When incidence of isease is

OR = (AD)/(BC)

OR = 8.88 means that 8 times more likely to have an MI with cocaine use!

Correlation Coefficient (r)

• r = -1 to +1
• The strength of the “relationship” between 2 variables whereas regression analysis provides the “predictability” of one variable on another variable.
• Correlation does NOT imply causation
• The closer the absolute value is to +1, the stronger the “correlation” or “relationship” between the 2 variables.
• The closer to -1 = no relationship

How to interpret an “r” value:

• Though a “strong association (i.e., r= close to +1) may exist between 2 variables, it does not “imply” that one event or variable “caused” another.
• The “r” value does not have the ability to determine which came first
• Another variable may also be influencing the relationship
• Most complex relationships can rarely be explained by only 2 variables
• Thus, Spearman and Pearsons Correlations are only descriptors of the “strength” and “direction” of the relationship

Coefficient of variation (r-squared)

• How much one variable can be explained or related to another
• also called coefficient of determination
• Example related to number of calories and weight gain:  If r=0.84, then r squared = 0.70; therefore 70% of the variation of Y is due to X
• This implies that 70% of the variability in wt gain or loss is attributed to the variability in the amount of cals consumed (or) it can also be said that the amount of calories consumed provides us with 70% of the information needed to predict weight gain or loss.

Regression Analysis

• Mathematical description or equation that provides the “predicctability” of one variable on another variable
• Provides “statistical control” of confounders
• Linear Regression - Relationship between 2 variables (1 independent and 1 dependent variable) - Uses line of best fit (y = mx + b)
• Multilinear Regression - Relationship between > 1 independent variable and 1 dependent variable
• Logistic Regression Analysis - which variables are important in predicting the outcome
  • A variable may not always be a significant influence on the outcome:
    • Main reason is no reln exists between the ind and dep variable
    • One variable is highly correlated with another variable already included in the regression and does not provide additional protective information
    • Lack of statistical power to detect a difference (usually from insufficient sample size).

Oh, Drugmonkey, Latisse Saved My Life

I love Drugmonkey; really I do. His wit and way of writing about all things drug related is inspiring. And I laugh as well. He has a new book coming soon (soon I hope) and an excerpt. And my response though keep in mind very tongue-in-cheek:

No, no, no Drugmonkey (@drugmonkey on Twitter) you just didn't bring up the one drug that has changed my life!  Ah Latisse!  The drug that has made my teeny tiny eyelashes longer without the glue or the accidentally falling off lash accident!

The drug that is only $75 here in my fair city because the demand must not be high.

Did you know you can make that tiny bottle last for months and not just one month?  Does that change your mind about this rip-off drug you so labeled?

Sadly, probably not because you would rather see a lady read a book.  I don't have any pictures of that much to the reader's dismay.

Hypotrichosis had severely limited my self-confidence to the point of being barely unable to function.  I could see the computer screen quite well but just knowing that I barely had any lashes to bat was disabling.  I had considered filing for disability with the government, but since the condition didn't affect my job (well at least in definition) I decided that I would move forward and find my own treatment.

Much to my delight, I found a little physician run botox/latisse/filler "clinic" and went in asking for help.

"Help," I pleased.  "My lashes aren't sexy."

The lady at the counter was moved with my brief history of disease and told me that Latisse was the cure.

I am cured.

Though my wallet is a bit tighter and my lashes are so long now I can barely see the computer screen, I can honestly say that having lashes as long as the Nile has been a complete turnaround in my life.  I am able to bat my lashes to and fro to achieve most anything (well, except it doesn't work on my children, yet) and not only that, I have this bit of discoloration right at the line of my lashes that mimics light brown eyeliner.  Win-win, right?

BCPS 2013: Statistics (Introduction)

Statistics are heavily covered on the exam. One of the things I did upon starting the test was to copy this graph on the front cover of my  test book and used it throughout.  Yes, it would be easier if there were sections:  statistics, cardiology, etc... but what you'll find are questions that jump from topic to topic.   I will do this again!  Memorize:

 

BCPS Changes: HUGE!

BPS Announces Changes to the 2013 Examination

BPS is pleased to announce the following changes for the 2013 Pharmacy Specialty examinations:

Computer-Based Examination Administration BPS examinations will move from paper and pencil format to computer-based administration. Please note the content outlines for the BPS specialty examinations remain the same. Content outlines are available for review under the "Specialties" tab on this page. For 2013, there will still be 200 questions on each BPS specialty certification examination and 100 questions on the recertification examinations. The multiple-choice format remains. Four possible answers are provided for each question, with only ONE designated as the correct or best choice. For initial certification candidates the schedule remains unchanged from previous years and is as follows:

Examination Part 1 (100 multiple-choice items): 2.5 hour testing period in the morning Optional break Examination Part 2 (100 multiple-choice items): 2.5 hour testing period in the afternoonCandidates will have the ability to go back to review or change answers while they are seated in the specific 100 question portion of the examination.

Awesome!  Can I tell you how I was having major flashbacks to the 1980s doing the old scantron?  So does this mean we will all be sitting in a computer lab?  No wonder they had to have expanded test dates.  This is good though.  Rather than ruining my whole entire weekend, I can take off during the week, hole up somewhere (hopefully Nashville) and then return to party with my kids on the weekend.  Because, I will be partying this time! 

Expanded Test Dates Rather than test on a single day, candidates can choose their own testing day within the test administration window beginning on Thursday, September 19, 2013 through Saturday, October 5, 2013. Please note that most testing centers are not open on Sundays.

Expanded Test Locations BPS has expanded from 80 test sites in 2012 to more than 450 domestic (U.S. and Canada) test centers as well as more than 200 international testing centers. This dramatic expansion is possible because of a new testing services agreement with Castle Worldwide, Inc. Founded in 1987 in North Carolina, Castle is one of the nation's leading certification testing companies. For a list of testing centers visit: https://www.castleworldwide.com/castleweb/clients/testing-services/ibt-testing-sites.aspx

2013 BPS Examination Registration Registration for the 2013 BPS examinations is scheduled to open during the first week in April, 2013. Candidates whose completed examination applications are approved first will receive scheduling priority. BPS examination registration will close on August 1, 2013.

For More Information The 2013 BPS Candidate's Guide will contain more information on the examination process and will be posted to the BPS website in March, 2013. Please continue to check the BPS website for updates and additional details.

SO what does this mean for waiting on the test results?  Anyone have any ideas?  Quicker, I hope.

Should you be recommending a proton pump inhibitor (PPI) or H2-receptor antagonist (H2RA) for stress ulcer prophylaxis in critically ill patients?

We know that PPIs are better than H2RAs at raising intragastric pH, but we don’t know whether this higher pH value translates to superior clinical outcomes.  In fact, there is some debate whether a higher pH could actually cause problems, like nosocomial pneumonia or Clostridium difficile infection.  Given that clinically important GI bleeding has been associated with a high mortality rate (48.5% vs. 9.1% in non-bleeders), it seems that selecting the best agent for stress ulcer prophylaxis is an important decision. This hotly-debated topic, reinvigorated by the 2012 Surviving Sepsis Campaign Guidelines’ grade 2D recommendation in favor of PPIs, has again been examined with a recent meta-analysis by Alhazzani et al published in the March 2013 issue of Critical Care Medicine.

Actual .pdf of meta-analysis.

Of course, this is not the first meta-analysis to examine the topic.  In fact, three other meta-analyses have been published since 2009.  Here, here, and here. Naturally, the authors of this most recent meta-analysis claim that their statistical analysis was superior, they included more relevant trials, and they excluded more inappropriate trials to make this analysis a more pure, scientifically-valid view of the data.

This meta-analysis combined 14 randomized controlled trials with 1,720 total patients.  The analysis concluded that PPIs were associated with a reduction in clinically important upper GI bleeding (1.2% vs. 6.4%, NNT 19, RR 0.36, p=0.002) and overt upper GI bleeding (3.8% vs. 15.7%, NNT 9, RR 0.35, p<0.0001).  There was no difference in nosocomial pneumonia, ICU mortality, or ICU length of stay.

Is it time for famotidine and ranitidine to hang up their hat in the ICU?  The evidence from this meta-analysis appears compelling at first glance, but diving deep into the manuscript reveals some troubling issues.

First, the included trials were not comparing similar treatments of H2RAs.  Some trials used continuous infusions, some used once daily dosing, and one did not report dose at all.  It is scientifically questionable to pool a variety of different H2RAs with different dosing strategies together into a single group and categorize the treatments as being the same.

Second, the included trials did not have consistent definitions for “clinically important bleeding” and “overt bleeding”.  Some trials used very strict definitions where bleeding had to be confirmed with EGD, others has very loose criteria (eg, hemodynamic instability not explained by other causes), and some did not even provide definitions.  Indicative of the questionable criteria, 5 of the 12 included trials had an event rate of 0% in both arms, whereas one trial had an event rate as high as 31%.

Third, one must question whether the endpoint of “clinically important bleeding” is a surrogate or a clinically relevant outcome.  Given the questionable definitions and criteria used, a firm endpoint like ICU mortality would be a definitive approach to concluding a victor.  Unfortunately, there was no difference in ICU mortality demonstrated in this meta-analysis (17.5% PPI vs. 21.2% H2RA, p=0.91).

Given the paucity of high-quality data examining PPIs versus H2RAs for stress ulcer prophylaxis, it can be extremely temping to favor meta-analyses to find an answer to this compelling question.  The fallacy in this approach, however, is that you cannot take a multitude of poor-quality trials (many with fewer than 50 patients in the H2RA arm) and somehow combine the data into a valid, reliable, unbiased manuscript on which you base your clinical practice.

So how should we interpret this meta-analysis?  In my view, until better quality evidence comes out, there is no proven difference in the prevention of stress ulcer prophylaxis between PPIs and H2RAs.  The decision should be made based on formulary considerations (cost and availability), formulation considerations (ability to be crushed), the patient’s history of using a particular agent prior to admission, and potentially drug interactions (although I believe the PPI/omeprazole debate has not been concluded).

Sean P. Kane is a critical care clinical pharmacist and the author of ClinCalc.com -- an evidence-based website with clinical tools and calculators for medical professionals.

Nexium photo:  Photo credit: License Some rights reserved by Rennett Stowe

High Yield Med Reviews: My Thoughts for the BCPS

High Yield Med Reviews is a site for high quality, yet affordable medical review courses and practice test banks for preparing for advancement of clinical competency (and board licensures) among healthcare professionals. I personally subscribed to their service last year months after spending money on the ACCP material to help prepare me for the BCPS Pharmacotherapy Exam 2012. Last year, this service only had Q-Bank and not the course Lectures that are added this year. This is a much more valuable addition for the price and solidifies my decision that this service is an equal if not superior contender to the ACCP materials generally bought.

The great thing about the High Yield Med Reviews service it is that the material covers the same topics and MORE for a lower cost. To say that $800+ for just the .pdf files of the ACCP is expensive is an understatement. The BCPS Online Review Course is only $299. It includes 1,700 practice questions and flashcards including biostatistics, access to the BCPS Online Lecture Center, and spiral bound notebook with all the lectures.

The Online Lecture Center shows something called Access to Lecture and shows how many times you can watch. You receive 2 redemptions per lecture. It is recommended to use one when studying the first time or when ready to tackle that particular topic and then the other closer to the time of the test. You have 24 hours per redemption which is like a DVD rental. This is nice in that it puts time constraints on the lectures. It is not nice in that it puts time constraints on the lectures. Limits make it hard but also force you to use them in the best possible conditions. Basically though, two should be enough if you plan to use them appropriately. Luckily you can watch on your iPad or iPhone.

The Q-Bank Questions is the section I used last year. It contains both the test and tutorial mode which is nice to help study and then quiz yourself on the material. Had I known about this service earlier (the added course lectures this year), I would have used it alone and not paid for the ACCP material (Therapeutics update) because it is more in-depth. The questions are of a more complex nature in wording, but cover the same concepts more in-depth than the actual test questions. In other words, I believe if you start now on studying the High Yield Med Reviews materials, there should be NO reason for you not to pass. You have to put in the time to get through the massive amount of material. See FAQ for more in-depth questions/answers of what this product will do.

No matter what, the amount of material on this test is very significant. If you have been out of school for just a short period of time, the material will be fresher in your mind. If you finished a residency, you are much more prepared. If you are like me and decided to do this as a personal goal (I graduated with a PharmD in 1999) you need to start studying MUCH earlier. The biggest challenge is finding ALL of the material you need. Guess what? There were actually topics ON the test itself that were not in the study materials I had or if were in the study materials not covered in enough detail to be able to answer the question correctly.

High Yield Med Reviews has material that encompasses all that you will need to pass. The material is a bit more in-depth than the ACCP material while being A LOT cheaper. For me, those two things make this a better buy.

If you have any questions, please feel free to leave a comment! And please follow along studying with us on the calendar!

BCPS Study Schedule 2013: Who is With Me?

The Study Schedule is posted in the menu above for those interested!  Basically I'm following a similar format as listed on Dr. Ted Williams BCPS Study Group.  

Basically this is it.  I have already started studying prior to today of course, but since it would do me good to have a written plan, I went ahead and added this.  I always worry that the BCPS studygroup website will go down.  Just in case:  (hope you don't mind Ted ;))

Ted's BCPS Study Tips (after passing in 2010)

Study Schedule

• Anders Westanmo has developed as must-use study schedule. http://www.bcpsstudygroup.com/
• I slacked off on the third lap, but still managed to pass.

Things to know

• Know the basic statistics cold.  (I agree 100% with this!!!)
  • You can't fake these and there are a lot of questions
  • Knowing wont guarantee passing, but not knowing will guarantee failing
• Know treatment algorithms - know guidelines -- FIRST, SECOND, and some THIRD LINE THERAPY
• Know indications for therapy
• Know contraindications to therapy
• Know therapeutic window for drugs with narrow/targeted window (e.g. Lithium)
• Know ADRs of significance
  • And if that ADR arises, how to change therapy (e.g. cough from lisnopril, switch to ARB)
• Know basic kinetics (e.g. volume of distribution, half life, dose adjustments based on plasma concentration, etc)
• Know major CYP interactions
  • know the drugs that strongly induce or inhibit
  • Know drugs which are major substrates, especially when inducers and inhibitors are likely to be co-administered (e.g. Seizures)
  • Know which way the plasma concentrations will go

Things not to worry about

• Exact doses for complex regimens (e.g. ICU insulin drip rate protocols)
• Complex statistical calculations
• Complex Kinetics (e.g. Vancomycin initial dose)
• Minutia of side effects (ie if you wouldn't change therapy, it's not a big deal)
• Obscure treatments for very obscure disorders

Final thoughts

• Just like NAPLEX, you can miss a bunch of questions and still pass (2010 passing was 67%) - 2011 was a 111/200 and last year 2012 was higher 123/200 I think?
• Test is designed to test practical application, not minute details, so focus on patient treatment
• The BCPS study group schedule will definitely prepare you.
  • I only did the first two cycles through and I was fine
  • Even if you get off schedule, if you go through the material twice, you'll definitely have a fighting chance
  • Spending 1 hour a night on the schedule will get you ready, don't stress
  • The Sample questions in the PSAPs,on the BPS website, and most in the study guide are NOT helpful
    • Not structured like the questions on the exam
    • Content is not validated
    • If you haven't taken an exam for a while, they might be helpful to get you back in the groove. But if you are taking the exam immediately after a residency and pharmacy school, don't worry about them. They will stress you out.

BCPS Topic Areas 2010

Key Statistical Tests to Memorize

Statistics

• Study Designs
• Inferential Statistics
• Variables
• Descriptive Statistics
• Sampling / Variability
• Hypothesis Testing
• Decision Errors
• Statistical Significance
• Confidence Intervals
• Statistical Tests
• Common Statistical Calculations
• Specificity
• Sensitivity
• Online Statistic References

Clinical Trials

Included from Clinical Trials

• Study Designs
• Bias
• Common Statistical Tests

Bone Joint Rheumatology

• Fibromyalgia
• Osteoarthritis
• Gout
• Osteoporosis
• Rheumatoid Arthritis
• Lupus

Pediatrics

• Sepsis
• Meningitis
• Respiratory Syncytial Virus
• Pediatric Viral Infections
• Otitis Media
• Immunizations
• Pediatric Seizure Disorder
• ADHD

Geriatrics

• Alzheimer's Disease
• Osteoarthritis
• Urinary Incontinence
• Benign Prostatic Hyperplasia

Kinetics

Describe Kinetics here.

Neurology

• Multiple Sclerosis
• Seizures
• Stroke
• Subarachnoid Hemorrhage
• Parkinson's Disease
• Migraine Headache
• Delirium
• Traumatic Brain Injury
• Tremors

BCPS Psychiatry

Affective Disorders

• Depression
• Bipolar Disorder
• Anxiety

Psychoses

• Schizophrenia & Antipsychotics

Miscellaneous

• Insomnia
• Drugs of Abuse

Fluid and Electrolytes & Nutrition

• Fluid Requirements
• Fluid Replacement
• Sodium
  • Hyponatremia
  • Hypernatremia
• Potassium
  • Hypokalemia
  • Hyperkalemia
• Magnesium
• Phosphorus
  • Hypophosphatemia
  • Hyperphosphatemia
• Calcium
  • Hypocalcemia
  • Hypercalcemia
• Acid Base Chemistry
• Acidosis
• Nutrition

Acute Cardiac Care

• Acute Decompensated Heart Failure
• Arrhythmia
• Acute Coronary Syndrome
• Pulmonary Hypertension
• Hypertensive Crisis
• Advanced Cardiac Life Support

Critical Care

• Acid Base Balance
• Respiratory Acidosis
• Sedation
• Mechanical Ventilation
• Delirium
• Therapeutic Paralysis
• Shock
• Sepsis
• Vasopressors

Endocrine

• Diabetes
• Acute Hyperglycemic Crisis
• Hyperglycemic Hyperosmolar State
• Diabetic Nephropathy
• Diabetic Retinopathy
• Diabetic Foot Infections
• Diabetic Foot Care
• Thyroid Hormone
  • Hypothyroidism
  • Hyperthyroidism
• Adrenal Disorders
  • Cushing's Syndrome
  • Addison's Disease
• Diabetes Insipidus
• Parathyroid Disorders
  • Hypocalcemia
  • Hypercalcemia
  • Hypoparathyroidism
  • Hyperparathyroidism
• Polycystic Ovary Syndrome
• Nephrolithiasis
• SIADH

Infectious Disease

• Antimicrobial Prophylaxis
• Osteomyelitis
• Prosthetic Joint Infections
• Meningitis
• Bacterial Meningitis
• Otitis Media
• Febrile Neutropenia
• Fungal Infections
  • Disseminated Candidiasis
  • Candiduria
  • Onychomycosis
  • Aspergillosis
• Gastrointestinal Infections
• Vaginitis
  • Vulvovaginal Candidiasis
  • Bacterial Vaginosis
  • Trichomoniasis
• Endocarditis
• Intra abdominal Infections
• Lung Abscess
• Opthalmic Infections
• Prostatitis
• Pneumonia
• Urinary Tract Infections
• Cellulitis
• Erysipelas
• Necrotizing Fasciitis
• Varicella
• Diabetic Foot Infections
• Osteomyelitis
• Peritonitis
• Clostridium Difficile

BCPS HIV

• HIV
• HAART
• Opportunistic Infections
• Antifungals

Gender Health Issues

• Osteoporosis
• HRT
• Lactation
• Pregnancy Complications
  • Premature Labor
  • Labor Induction
• Contraception
• Sexually Transmitted Diseases
• Vaginitis
  • Vulvovaginal Candidiasis
  • Bacterial Vaginosis
  • Trichomoniasis
• Prostatic infections
• Erectile Dysfunction
• Endometriosis
• Infertility
• Menstrual Disorders

Ambulatory Cardiology

• Heart Failure
• Atrial Fibrillation
• Hypertension
• Coronary Heart Disease
  • Hyperlipidemia
  • Myocardial Infarction
• Angina
• Pulmonary Hypertension
• Peripheral Vascular Disease

Ambulatory Care

• Anticoagulation/Antiplatelet Agents
• Hyperlipidemia Pocket Guide
• Adult Immunizations

Gastrointestinal Disorders

• GERD
• Peptic Ulcer Disease
• SUP
• GI Bleeding
• Irritable Bowel Syndrome
• Irritable Bowel Disease
• Liver Cirrhosis
• Viral Hepatitis
• Pancreatitis

Nephrology

• Acute Renal Failure
• Drug Induced Renal Disease
• Chronic Kidney Disease
• Renal Replacement

Oncology Support

• CINV
• Pain Management
• Febrile Neutropenia
• G-CSF
• Thrombocytopenia
• Cytoprotective Agents
• Oncology Emergencies
• Methotrexate/Leucovorin
• Extravasation

Hematology

• Anemia
• Coagulation Disorders
• Disseminated Intravascular Coagulation
• Sickling Disease

Oncology

• Breast Cancer
• Colon Cancer
• Ovarian Cancer
• Cervical Cancer
• Endometrial Cancer
• Leukemia
  1. Acute Lymphoblastic Leukemia (ALL)
  2. Chronic Lymphoblastic Leukemia (CLL)
  3. Acute Myelogenous Leukemia (AML)
  4. Chronic Myelogenous Leukemia (CML)
• Lung Cancer
• Prostate Cancer
• Skin Cancer
  • Actinic Keratosis
  • Basal Cell Carcinoma
  • Squamous Cell Carcinoma
  • Melanoma
  • Xeroderma Pigmentosum

Dermatologic Disorders

• Acne
• Burns
• Dermatitis
• Decubitus Ulcers
• Psoriasis - Please don't forget this one.  I DID.
• Urticaria

Eyes Ears Nose Throat

• Allergic Rhinitis
• Glaucoma
• Age-Related Macular Degeneration
• Vertigo

Immunologic

• Anaphylaxis
• Angioedema
• Organ Transplant
• Stevens-Johnson Syndrome

Pulmonary Disorders

• Asthma
• COPD
• ARDS
• Sleep Apnea

CDC's National Influenza Campaign: Flu Activity Still High

Flu activity is still high across the country and CDC wants to make sure people know the importance of getting vaccinated and caring for yourself and loved ones who are sick. CDC recommends “take 3 actions” to fight the flu – get vaccinated, take every day preventative actions to stop the spread of germs (avoid sick people, stay home when you’re sick, cover your nose and mouth and wash your hands), and take antiviral drugs if your doctor prescribes them.

·         CDC recommends a yearly flu vaccine as the first and most important step in protecting against flu.

·         U.S. flu season continues; influenza-like-illness has fallen in the East and risen sharply in the West.

·         The timing of flu is very unpredictable and can vary from season to season. Flu activity most commonly peaks in the United States in January or February. However, seasonal flu activity can begin as early as October and continue to occur as late as May.

·         Symptoms of the flu may include fever, cough, sore throat, runny nose, body aches, headaches, and fatigue.

·         For information on weekly flu activity, please visit http://www.cdc.gov/flu/weekly/fluactivitysurv.htm

·         People seeking vaccination may need to call more than one provider to locate vaccine at this time. The flu vaccine finder at http://flushot.healthmap.org/ may be helpful.

·         Antiviral treatment can avert serious outcomes and should begin as quickly as possible in high risk persons, including people 65 and older, young children, pregnant women, and people with certain underlying conditions like asthma, heart disease, diabetes and neurological disorders.

·         While antiviral drugs work best when given within 48 hours of symptom onset, observational studies have shown that giving antivirals 48 or more hours after symptom onset can still prevent serious flu-related outcomes.

-- From CDC Message to Readers About 2012-2013 Flu