Download Clin IQ 2015 - Jacobs School of Medicine and Biomedical Sciences

Volume 1, Issue 1
06/01/2015
University at Buffalo,
Family Medicine Residency Program
Clin IQ 2015
UB Family Medicine Residency Clin IQ Program
What is PICO?

PICO is an acronym
for the components
of a well-built clinical question. All
ClinIQs are based on
PICO

P=patient, always
your primary focus.

I=intervention, what
are you proposing to
do (not do, e.g.,
watchful waiting).

C=compared to
what? Some questions (e.g., causation) won’t have a
comparison.

What is Clin IQ Program?
Purpose
Clinical Inquires (Clin IQ) program is
based on the evidence based literature search of clinical questions
relevant to patient care and helps
residents, faculty and community
physicians to enhance their
knowledge and scholastic activities.
1. Compliance with ACGME residency review committee (RRC) requirement for the residents and faculty
participation in scholarly activities.
Our program was started in June
2014 under the guidance of program
director Dr. Diana Wilkins and core
faculty team. UB Family Medicine
Clin IQ program is adopted from Clin
IQ process of Oklahoma Clinical and
Translational Science Institute.
We appreciate the tremendous help
and support provided by Primary
Care Research Institute (PCRI) especially Drs. Ranjit Singh , Chet Fox and
Nikhil Satchidanand.
O=outcome, what
do you want to
happen
Inside this issue:
Influenza vaccine and
Pneumonia risk
1
Dry needling vs. anesthetics for trigger points
3
Resuming warfarin therapy in Atrial fibrillation
4
Risk of new onset Diabetes in patients on Statins
6
Low dose Aspirin and
preeclampsia related
7
Systemic corticosteroids
for chronic rhino-sinusitis
9
2 To facilitate and nurture the scholarly activities in the realm of busy
clinical practice.
3. Provide evidence based answers
to clinical questions and a link between academic and community
physicians.
Team
UB Family Medicine class of 2015
Core faculty team
Note: Current issue of Clin IQ is for appreciation of residents hard work and effort
and is not intended for CLINICAL or peer
reviewed publication purpose.
Level of evidence is based on the
algorithm on Page 10
Source: http://aafp.org/afp/2004/
0201/0548.html.
Clin IQ 1: In adults and the elderly who are generally healthy, does administration of the
influenza yearly vaccine reduce the incidence and/or severity of influenza associated
pneumonia?
Authors: Jennifer Yerke-McNamara
MD.& Kevin C. Lesh MD
Faculty Mentor: David Newberger
MD
Residency Program: SUNY Buffalo
Family Medicine, Millard Fillmore
Suburban/Amherst Track
Answer: Yes
Level of Evidence : B
Search Terms: influenza vaccine,
pneumonia
Date Search was Conducted:
Exclusion Criteria: Patients under
November 2014 in Pubmed. Assistance received by Medical Librarians
at Millard Fillmore Suburban Hospital.
age 18 years
Inclusion Criteria: Published systematic reviews/meta-analyses,
clinical trials, cohort studies comparing the development and mortality of
influenza associated pneumonia.
Summary of the Issues
Worldwide, pneumonia is a common illness affecting all ages, with
an estimate of approximately 450
million cases per year.1
Clin IQ 2015
Clin IQ 1 (Contd.)
Of the varying etiologies, viruses are a common cause
of community-acquired pneumonia with an estimated incidence of
49%. 1 Common isolated viruses
include RSV (11%) and influenza
virus (10%). 1 Typically influenza
inoculation is a self-limited upper
airway illness, but severe complications include viral pneumonia
and/or secondary bacterial pneumonia leading to ICU admissions
and death at times. 1 It is estimated that 65,000 deaths per
year are attributed to the combination of influenza and pneumonia in
the USA. 2 Those affected most
severely include the elderly and
adults with chronic medical conditions. 1,2
The influenza vaccination is an immunization that is
recommended annually for all
persons over age 6 months old. 2
It induces immunity by leading to
the production of antibodies
against the specific influenza
strains contained within the vaccine. This is true regarding both
the typical trivalent vaccine, as
well as the quadrivalent vaccine
that is also available in adult and
pediatric formulations. Trials and
“For adults older than 65,
the influenza vaccine
reduces the risk of
pneumonia as well as
mortality from pneumonia.”
Page 2
studies assessing the efficacy
of the vaccines are limited due
to ethical considerations. 2
However, of the studies available, results show immunization
with the vaccines leads to reductions in both associated
pneumonia development and
subsequent hospitalizations,
morbidity, and mortality. 2
Summary of Evidence
A 2007 cohort study
evaluated the impact of prior
influenza vaccination on inhospital mortality and other
health outcomes among hospitalized patients with community
-acquired pneumonia. Study
subjects were adults 18 and
older who were admitted to the
hospital with a diagnosis of CAP
between November to April
1999-20033. A total of 17,393
individual records were analyzed3. Vaccination status was
available for 8251 study subjects (47%) and 1590 (19%)
had a record of current influenza status3. All-cause mortality
occurred in 1245 (7%) of individuals3. Those individuals with
documented current influenza
vaccine were less likely to die
during hospitalization compared with documented nonrecipients of the vaccine3.
A 2006 study examined the effect of annual influenza vaccination on the occurrence of lower respiratory tract
infections in elderly, community
-dwelling patients4. A population based cohort study was
performed using a Primary Care
Information database in the
Netherlands4. The study was
comprised of patients aged 65
years and older, whose individual cumulative exposure to the
influenza vaccination was computed4. The risk of lower respiratory track infection (LRTI) in
those who were vaccinated or
re-vaccinated was compared to
the unvaccinated using a multivariate Cox proportional hazard
model4. The study looked at the
treatment of LRTIs in the primary care setting4. The study consisted of 26,071 subjects,
3,412 of who developed an
LRTI4. 1,295 of those patients
that developed a LRTI developed pneumonia and 455 of
those patients were admitted to
the hospital for treatment4.
Vaccination rates varied the
study population and had a
range of 64%-74%4. Those with
co-morbid conditions had a
higher vaccination rate of 7479%4. During the influenza
epidemic period, a first influenza vaccination was associated
with a 71% risk reduction (95%
CI, 4%-90%) of hospitalized
pneumonia4. No significant
association was seen during
with revaccination during this
period4. The data of the study
concluded that influenza vaccination reduces the risk of
lower respiratory track infection
in specific subgroups during the
influenza epidemic period4.
Conclusion: From
our search of the literature, we
can conclude that for adults
older than age 65 the influenza
vaccine reduces the risk of
pneumonia as well as mortality
from pneumonia. The influenza
vaccine was shown to decrease
the incidence of pneumonia
during the influenza epidemic
period4. A decrease in mortality
of those with pneumonia was
seen in those who received an
influenza vaccine3. This finding
does change the way we practice as we can now tell patients
that not only is their risk of
contracting influenza decreased
by receiving a vaccination, but
so is their risk of developing
pneumonia. This may help
encourage people to get an
annual influenza vaccine.
References:
1.Ramsey C, Kumar A. Influenza
and Endemic Viral Pneumonia.
Crit Care Clin 2013; 29: 10691086
2.Chertow D, Memoli M. Bacterial Coinfection in Influenza A
grand Rounds Review. JAMA
2013; 3: 275-282.
3.Spaude, K, Abrutyn E, Kirchner
C, Kim A, Daley J, Fisman D.
Influenza Vaccination and Risk
of Mortality Among Adult Hospitalized with Community-Aquired
Pneumonia. Arch Intern Med.
2007; 167:53-59
4.Voordouw C, Sturkenboom M,
Dieleman J, Stijnen T, Lei J,
Stricker B. Annual Influenza
Vaccination in CommunityDwelling Elderly Individuals and
the Risk of Lower Respiratory
Tract Infections or Pneumonia.
Arch Intern Med.
2006;166:1980-1985
“Sometimes when you
innovate, you make Mistakes. It is best to admit
them Quickly and get on
with improving your
other innovations.”
-Steve Jobs
Volume 1, Issue 1
Clin IQ 2: In patients with myofascial trigger points, can dry needling be just as effective as
injections with an anesthetic solution?
Authors: Angela Barnes DO,
Carlyle Martis MD, Raena
Singh MD
Faculty Mentor: Priyanka Patnaik MD
Residency Program: University
at Buffalo, Family Medicine
Residency Program. Buffalo
General / Jefferson Track
Answer: Yes
Our research found that dry
needling can be as effective,
however it is associated with
side effects. These include
more pain for the patient during the procedure and needle
placement for optimal pain
relief is examiner dependent.
Level of Evidence: A
Search Terms: dry needling,
trigger points, dry needling vs
wet needling, lidocaine injection.
Date search was conducted:
May 2015
Inclusion Criteria: systematic
review of randomized control
trials to evaluate whether dry
needling is effective.
Exclusion Criteria: Studies
involving patients with Fibromyalgia.
Summary of Issues:
Myofascial trigger points are defined as discrete, focal, irritable
spots felt as a nodule or taut band
of skeletal muscle. Patients with
trigger points experience pain
locally, when these points are
palpated and their pain will be
Page 3
reproduced on exam. Acute injury
or repetitive microt-rauma can
also result in the stress on muscle
fibers and the formation of trigger
points.
Many different techniques are
currently used to inactivate trigger
points to assist patients with pain
relief/control. These include traditional physical therapy, ultrasonography, manipulative therapy and
injections. Trigger-point injections
have been shown to be one of the
most effective treatment options
to quickly and effectively treat pain
associated with myofascial trigger
points.
Summary of Evidence
An injectable solution of 1% lidocaine or 1% procaine is usually the
solution of choice. Procaine has
been found to have the least myotoxic effects. Other solutions such
as diclofenac, botulinum toxin type
A (Botox), and corticosteroids,
have also been used in triggerpoint injections, however, these
substances have been associated
with significant myotoxicity and
visible skin defects.
In the systematic review of randomized control trials by Cummings et al2, they concluded that
when treating myofascial trigger
points the nature of the solution
injected did not change outcomes.
And more importantly, wet needling was not found to be therapeutically superior to dry needling.
Dry needling has been associated
with post-injection soreness. In
Hong et al3 it was concluded that
this pain was different from the
original myofascial pain. Therefore, that study concluded that to
reduce this soreness an anesthetic
solution could be injected. Howev-
er, it did not significantly change
the long term outcome of pain
relief. Each patient should be reevaluated however, and they recommended that no reinjection of
the trigger points until the postinjection soreness resolves, which
typically lasts for 3 to 4 days in
length. Providers should encourage patients to stay active even
while receiving injections, and this
would include various stretches
and putting their muscles through
a full range of motion to help ensure optimal outcomes.
2.Cummings TM, White AR. Needling
therapies in the management of
myofascial trigger point pain: a systematic review. Arch Phys Med Rehabil. 2001 Jul;82(7):986-92.
3.Hong CZ. Lidocaine injection versus
dry needling to myofascial trigger
point. The importance of the local
twitch response. Am J Phys Med Rehabil. 1994;73:256–63.
4.Imamura ST, Fischer AA, Imamura
M, Teixeira MJ, Tchia Yeng Lin, Kaziyama HS, et al. Pain management using
myofascial approach when other
Conclusion:
Pain associated with myofascial
trigger points can significantly
affect a person’s quality of life.
Based on this review, we found
that dry needling of myofascial
trigger points is just as effective in
treating pain as wet needling using
an anesthetic solution. Given that
some patients can develop myotoxicity from anesthetic solutions,
dry needling is a good option for
pain relief. However, for those
who are able to tolerate these
anesthetics wet needling may help
minimize post-injection soreness
and decrease pain associated with
the actual trauma of the needle
during injections. After review of
the literature, we found that outcomes are usually equivalent
when comparing dry needling vs.
wet needling, but we suggest always taking into consideration
each patient’s individual needs.
References:
1.Simons DG, Travell JG, Simons
LS. Travell & Simons' Myofascial
pain and dysfunction: the trigger
point manual. 2d ed. Baltimore:
Williams & Wilkins, 1999:94–173.
“Dry needling of myofascial
trigger points is just as
effective in treating pain as
wet needling using an
anesthetic solution .”
Clin IQ 2015
Clin IQ 3: : In patients with atrial fibrillation (AF) on warfarin and recent gastrointestinal
bleed (GIB), should patients resume warfarin to prevent all-cause mortality?
Authors: Nathan Strauss
MD,Saman Razzaghi MD, Rachel
Larivee MD
Faculty Mentor: M. Ghazi MD
Residency Program: University
at Buffalo, Family Medicine Residency Program. ECMC/Clevehill
Track
Answer : Yes
Level of Evidence : B
(Retrospective cohort studies)
Search Terms: atrial fibrillation,
gastrointestinal bleed, warfarin, all
-cause mortality
Date Search was conducted:
December 2014.
Inclusion Criteria: Published
systematic reviews/meta-analysis,
cohort studies, and clinical research trials comparing risk of
restarting vs not restarting warfarin in patients with AF after any
gastrointestinal bleed (GIB).
Exclusion Criteria: Patients
other than those with AF as the
primary reason for anticoagulation
were excluded.
Summary of issues:
AF is one of the most common
clinically significant cardiac arrhythmias and is major risk factor
for thromboembolism and death.1
Warfarin has been the anticoagulant agent of choice for the last 3
“Restarting warfarin after 7
days was not associated with
increased risk of GIB, but was
associated with decreased risk of
mortality and thromboembolism
compared with resuming after
30 days of interruption.”
Page 4
decades in patients with nonvalvular AF, since it prevents
thromboembolism and has
mortality benefits over the
patients who are not treated
with warfarin.2 However, the
use of warfarin is not without
risks. Patients on warfarin are
at risk of hemorrhage. The
most common and fatal sites
are the gastrointestinal tract
and brain.3 GIB occurs in up to
15% of patients on long-term
anticoagulation.4 The risk of
bleeding is increased by the
intensity of anticoagulant therapy, age (over 65 years), concurrent use of aspirin and history
of GIB.5
Therefore, restarting warfarin
after GIB is a risky and often
difficult decision. In the literature, it appears as though the
debate is focused less on
whether or not to restart warfarin after a GIB, and more on the
various outcomes based on
duration of interruption of therapy.
Restarting warfarin after GIB
has shown to not only improve
cardiovascular mortality but
also quality of life.6 It is important to understand the risks
not only of mortality, but also
recurrent GIB, and thromboembolism in the context of resuming warfarin after a GIB.7 From
a patient’s perspective, the allcause mortality is the most
meaningful outcome to evaluate, since this encapsulates all
causes of risk to which a patient might be subjected. The
aim of this paper is to answer
the following question: In patients with AF on warfarin and
previous GIB, should patients
resume warfarin to prevent allcause mortality?
Summary of Evidence:
Two studies were examined to
determine if warfarin should be
restarted in patients with AF
and previous GIB to prevent allcause mortality. One study, by
Qureshi et al. (2014)7 hypothesized that warfarin treatment
prevents thromboembolism and
has mortality benefit when
compared to subjects who are
not restarted on warfarin after
major GIB in patients with AF.
They also investigated the various durations of interruption of
warfarin therapy and the risk of
GIB, thromboembolism, and allcause mortality. Using a retrospective cohort study, they
enrolled 1,329 subjects (mean
age 76 years, woman 45%), in
which warfarin was restarted
after GIB in 653 cases (49.1%).
They concluded that warfarin
restarted after 7 days was not
associated with increased risk
of GIB but was associated with
decreased risk of all-cause
mortality (hazard ratio (HR)
0.67) and thromboembolism
compared with resuming after
30 days of interruption.
mortality in the group that resumed warfarin was 5.8%, compared to 20.3% of patients that
did not resume warfarin. The
adjusted analysis confirms that
resuming warfarin reduced allcause mortality (HR 0.31).
Resuming warfarin therapy 1 to
7 days after a GIB resulted in
less thrombotic events but increased risk of recurrent bleeding. Overall, the risk of all-cause
mortality decreased with resumption of warfarin.
Conclusion:
We concluded that for many
patients who have experience
warfarin-associated GIB, the
benefits of resuming anticoagulant therapy outweighs the risks.
Qureshi et al. (2014)7 stratified
the duration of warfarin interruption, and conclude that restarting warfarin after 7 days
was not associated with increased risk of GIB, but was
associated with decreased risk
of mortality and thromboemboAlso using a retrospective cohort study, the second study by lism compared with resuming
Witt et al. (2012)8 evaluated the after 30 days of interruption. It
has been demonstrated by Witt
incidence of thrombosis, recuret al. (2012)8 that resuming
rent GIB, and all-cause mortaliwarfarin is best done between
ty, as well as the time to redays 7 to 90 to decrease TBE
sumption of anticoagulation,
and all-cause mortality. Based
during the 90 days following a
on these two studies, the overall
GIB. Patients were put into a
recommendation is to restart
group based on whether they
resumed warfarin therapy after warfarin between days 7 to 90
to reduce not only all-cause
GIB and followed up for 90
mortality, but also risk of TBE.
days. Of those who did not
restart warfarin, 2.5% of paLimitations: For this topic to be
tients had a thrombotic event
relevant to current practice,
compared to 0.4% of patients in
using warfarin as the only antithe resumption of warfarin
coagulant is limiting, since there
group. Regarding recurrent GIB,
are other newer anticoagulants,
10% of patients who restarted
such as Apixaban (Eliquis) and
warfarin had another episode of
Dabigatran (Pradaxa) that need
GIB, compared to 5.5% of pato be studied.
tients who did not restart warfarin and still had a recurrent GIB. Future studies need not only
This data was not statistically
address other types of anticoagsignificant and not dependent
ulation, but also all-cause moron dose of Coumadin. All-cause
Volume 1, Issue 1
Clin IQ 3 (Contd.)
tality, since is one of the most important outcomes of restarted
warfarin after GIB. Randomized
controlled trials are needed in this
area, since most of the current
studies involve cohort studies.
References:
1. Camm AJ, Kirchhof P, Lip GY,
Schotten U, Savelieva I, Ernst S,
Van Gelder IC, Al-Attar N, Hindricks
G,Prendergast B, Heidbuchel H,
Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J,
Goette A, Gorenek B, Heldal M,
Hohloser SH, Kolh P, Le Heuzey JY,
Ponikowski P, Rutten FH. Guidelines for the management of atrial
fibrillation: the Task Force for the
Management of Atrial Fibrillation
of the European Society of Cardiology (ESC). Eur Heart J 2010; 32:
2369-2429.
2. Mant JW. Pro: ‘Warfarin should
be the drug of choice for thromboprophylaxis in elderly patients with
atrial fibrillation’. Why warfarin
should really be the drug of choice
for stroke prevention in elderly
patients with atrial fibrillation.
Thromb Haemost 2008; 10: 14-15.
3. Suehiro T, Yakeishi Y, Sakai F,
Matsuzaki K, Sanefuji K, Toyokawa
T, Shoishita K, Sugie Y, Okudaira Y,
Kano T, Mine H, Suetsugu K,
Suetsugu F, Suehir N, Suhir K.
Gastrointestinal bleeding and
blood transfusion in the elderly in
Japan. Hepatogastroenterology
2012; 59: 1480-1483.
of elderly people with atrial fibrillation. Age Ageing 2007; 36:95-97.
4. Lee JK, Kang HW, Kim G, Kim
JS, Jung HC. Risks related with
withholding and resuming anticoagulation in patients with nonvariceal upper gastrointestinal
bleeding while on warfarin therapy. Int J Clin Pract 2012; 66:6468.
7. Qureshi W, Mittal C, Patsias I, Garikapati K, Kuchipudi A, Cheema G, Elbatta M, Alirhayim Z, Khalid F. Restarting
anticoagulation and outcomes after
major gastrointestinal bleeding in atrial
fibrillation. Am J Cardiol 2014; 113:
662-668.
5. Ladefeld CS, Beyth RJ. Anticoagulant-related bleeding: clinical
epidemiology, prediction, and
prevention. Am J Med 1993; 95:
315-328.
6. Das AK, Willcoxson pD, Corrado
OJ, West RM. The impact of longterm warfarin on the quality of life
8. Witt DM, Delate T, Garcia DA, Clark
NP, Hylek EM, Ageno W, Dentali F,
Crowther MA. Risk of Thromboembolism, Recurrent Hemorrhage, and Death
After Warfarin Therapy Interruption for
Gastrointestinal Tract Bleeding. Arch
Intern Med 2012; 172(19): 1484-1491.
Table 1: Summary of key research findings.
Reference
number
Objective
Type of
Study
Number of
Subjects
Intervention
Outcomes & Statistical Significance
7
Determine whether warfarin treatment prevents
TBE & has allcause mortality
benefit over subjects not restarted
on warfarin.
retrospective
cohort study
1329
Restarting
warfarin
Decision to restart warfarin after an
episode of major GIB is associated
with:
Mortality: Decreased all-cause mortality (HR 0.67, 95% CI 0.560.81)
TBE: Decreased TBE (HR 0.71, 95%
CI 0.54-0.93)
Recurrent GIB: No increased risk of
GIB (HR 1.18, 95% CI 0.941.10).
Restart Warfarin: > 7 days.
Determine the
incidence of
thrombosis, GIB or
all-cause mortality
and when to restart on warfarin
in a 90-day interval following a
warfarin associated GIB.
retrospective
cohort study
Restarting
warfarin
Warfarin therapy resumption after
GIB was associated with:
Mortality: Decreased all-cause mortality (HR 0.31; 95% CI 0.150.62)
TBE: Decreased TBE (HR, 0.05; 95%
CI 0.01-0.58)
Recurrent GIB: No increased risk of
GIB (HR 1.32; 95% CI 0.503.57).
Restart Warfarin: > 7 days, but < 90
days.
8
mean age 76
years old
45% women
Abbreviations: HR: hazard ratio, CI: confidence interval
Page 5
442
mean age
74.2 years old
49.8 women
Clin IQ 2015
Clin IQ 4: : In a patient with hypercholesterolemia, does statin use increase the
risk of developing new onset diabetes?
Authors: Samad Khan MD,
Enaame Farrell
Faculty Mentor: Masashi Ohira
MD, M. Ghazi MD
Residency Program: University
at Buffalo, Family Medicine Residency Program. ECMC/Clevehill
Track
Answer : Yes
Level of Evidence : A
Search Terms: statin therapy,
hyperglycemia, new onset Diabetes
Date Search was conducted:
January 2015
Inclusion Criteria: Published
systematic reviews/meta-analysis,
cohort studies, and clinical research trials looking at the use of
statin therapy on development of
Diabetes Type 2.
Exclusion Criteria: Patients who
were on statin therapy for indications other than hyperlipidemia
Summary of issues:
Recently the centers for disease
control and prevention (CDC)
released statistical data on the
ever-growing epidemic of diabetes which pose a threat to our
society. As supported by the
CDC the cost in billions of dollars in 2014 is estimated at
approximately $245 billion in
total medical costs and lost
work and wages, in addition,
the numbers have been rising
steadily to approximately 29
million people in the United
States. One out of three Americans are at risk of getting diabetes.
The fight against metabolic
syndrome and the early onset
of cardiovascular disease, has
prompted many clinicians to
prescribe statin medications. The use of statins in modern evidence based treatment
regimens is known to reduce
the relative risk of occurrence
of coronary event, cardiovascular disease mortality, non-fatal
strokes and all-cause mortality. But what if the treatment
implemented to stave off cardiovascular disease is
now implicated in causing the
early onset of type two diabe-
tes? A recent article found that
statin therapy is associated with
a slightly increased risk of development of diabetes, but the
risk is low both in absolute
terms and when compared with
the reduction in coronary
events. Clinical practice in patients with moderate or high
cardiovascular risk or existing
cardiovascular disease should
not change.
Summary of the Evidence:
Recently, there have been clinical trials of statin therapies that
have conflicting findings on the
risk of developing diabetes
mellitus in patients who were
given statins. In a 2009 study
1, it was investigated whether
Atorvastatin might decrease
insulin sensitivity and hyperglycemia in patients with hypercholesterolemia. This was a
randomized, single-blind, placebo-controlled parallel study.
Atorvastatin 10, 20, 40, and
80mg significantly increased
fasting plasma insulin with
mean changes of, 25%, 42%,
31%, and 45% respectively and
hemoglobin A1C levels (2%, 5%,
5%, an 5%, respectively when
compared to baseline or placebo. This rise in Hga1c levels
were evident after only 2
months of treatment. Atorvastatin also decreased insulin
sensitivity (mean changes
1,3,3,4 % respectively). The
study’s primary outcome of
higher HgA1c levels with
Atorvastatin was statistically
significant. This was also associated with increased fasting
insulin levels, lower adiponectin
and reduced insulin sensitivity.
This reduction in insulin sensitivity is the strongest evidence for
why there is glucose intolerance
with Atorvastatin.
In a meta-analysis 2 of published and unpublished trials
from 1994 to 2009, study was
done on the relationship between statin use and development of diabetes. This analysis
included trials with more than
1000 patients only with identical follow-up and duration of
more than 1 year. The study
showed that in 13 statin trials,
out of 91,140 participants,
4278 developed diabetes during
a 4 year period. Statin therapy
Table 1 Association between Statin Therapy and New Onset DM (Diabetes Mellitus)
Study name
Total number (n)
in Control Group
New DM Assigned
Statin
New DM in Control
Group
Level of Evidence
ASCOT-LLA
(Anglo-Scandinavian Cardiac Outcomes Trial
-Lipid Lowering Arm)
Atorvastatin 10mg or placebo (double blind)
3863
154 (3.9%)
134 (3.5%)
A
HPS
( Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk
individuals: a randomized placebo controlled
trial)
Simvastatin 40 mg or placebo (double blind)
JUPITER
(Justification for the Use of Statins in Primary
Prevention: An Intervention Trial Evaluating
Rosuvastatin trial)
Rosuvastatin 20mg or placebo (double blind)
7282
335 (4.6%)
293 (4.0%)
A
8901
270 (3.0%)
216 (2.4%)
A
Page 6
Clin IQ 2015
Clin IQ 4 (Contd.)
was associated with a 9% increased
risk for incident diabetes (odds ratio
[OR] 1·09; 95% CI 1·02–1·17). Metaregression showed that risk of development of diabetes with statins
was highest in trials with older participants, but neither baseline bodymass index nor change in LDLcholesterol concentrations accounted for residual variation in risk.
Treatment of 255 (95% CI 150–
852) patients with statins for 4
years resulted in one extra case of
diabetes. Heterogeneity between
the trials was low meaning that
most variation was due to chance
alone. The results showed that
individual assigned statins were at a
slight increased risk of diabetes
compared with those assigned pla-
“The small risk of
development of Diabetes is
outweighed by cardiovascular
benefit in most patients.”
cebo or standard care. Another
explanation for the relationship
between statin therapy and incidental diabetes is due to residual
confounding factors. Some of
these factors may be improved
survival with statin therapy, or a
change to a healthy lifestyle (i.e.,
weight loss) after cardiovascular
events, which are more likely in
placebo than statin groups. Overall survival with statins is very
similar to survival with control
therapy.
well as LDL-cholesterol concentrations in these participants showed
no direct correlation to increasing
residual variation in risk.
It is known that one in four Americans ages 45 and older are taking
a Statin. Based on that assumption, that equates to approximately 32 million Americans currently
taking a Statin. With these numbers in mind, the implications can
have lasting effects on the common practice of how these relatively safe drugs are prescribed.
In a meta-analysis of 6 large randomized trials, there have been
conflicting results. In the Jupiter
trial, more than 17000 adults
included in a double blind study
using Rosuvastatin and its effect
on blood sugar. All of these trials
were double blind studies and
painted a clinical picture of how
statins affect patient’s blood sugars. The major issue in determining whether or not statins raised
the risk of diabetes was, what
would be done with the results.
The fact is statins are mostly well
tolerated drugs that significantly
reduce cardiovascular events.
Conclusion:
When stating the ill effects of
statin therapy on a subgroup of
participants, statin therapy has an
associated 9% increased risk for
incident Diabetes. 1 The authors go
on to say that, the risk of development of diabetes with statin drugs
was highest in trials with older
participants. In the article it is
stated that the body mass index as
In view of the overwhelming benefit of statin for reduction of cardiac
events, the small risk of development of Diabetes is outweighed by
cardiovascular benefit in most
patients. Therefore we suggest
that clinic practice for statin therapy does not need to change for
patients with moderate to high
cardiovascular risk. It should also
be noted that in patients with type
2 diabetes the benefits of lowering
glucose levels remains unclear. In
recent clinical trials, improving
glycemic control did not reduce
cardiovascular events. The risk of
diabetes discussed in these articles should not be taken lightly,
and in patients who have low risk
cardiovascular pathology, serious
discussion should take place.
References:
analysis of randomized statin
trials. Lancet 2010; Volume 375,
No. 9716, p735–742, 27.
2. Coleman CI, Reinhart K, Kluger
J, White CM. The effect of statins
on the development of new-onset
type 2 diabetes: a meta-analysis of
randomized controlled trials. Curr
Med Res Opin 2008; 24:1359–62.
3. Freeman DJ, Norrie J, Sattar N,
et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment
effect in the West of Scotland
Coronary Prevention Study. Circulation. 2001 Jan 23;103(3):35762.
4. Ridker PM, Danielson E, Fonseca FA, et al., for the JUPITER Study
Group. Rosuvastatin to prevent
vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;
359:2195–207.
5. Sever PS, Dahlof B, Poulter NR,
et al., ASCOT investigators. Prevention of coronary and stroke events
with atorvastatin in hypertensive
patients who have average or
lower-than-average cholesterol
concentrations, in the AngloScandinavian Cardiac Outcomes
Trial-Lipid Lowering Arm (ASCOTLLA): a multicenter randomized
controlled trial. Lancet 2003;
361:1149–58.
1. Sattar N, Preiss D, Murray H, et
al. Statins and risk of incident
diabetes: a collaborative meta-
Clin IQ 5: In pregnant women at increased risk for preeclampsia, dose low-dose aspirin
prevent morbidity and mortality associated with preeclampsia?
Answer: Yes
Authors: Stacey ShawGugino MD, Sarah Morris MD
Faculty Mentor: David Newberger MD
Residency Program: SUNY
Level of Evidence: A
controlled trials and metaanalyses on Aspirin use for pregnant patients with preeclampsia
Search Terms: Preeclampsia.
Exclusion Criteria:Non-pregnant
Low dose aspirin
females
Buffalo Family Medicine, Millard
Fillmore Suburban/Amherst
Track
Date search was conducted:
Summary of Issues:
January 2015
Inclusion Criteria: Randomized
Page 7
Preeclampsia is a leading cause of
maternal death and affects 2-8%
of pregnancies throughout the
world. The rate of severe
preeclampsia continues to rise and
perinatal mortality is two times
higher in pregnancies affected by
preeclampsia. Of all maternal
deaths, 12% are related to
preeclampsia.
Volume 1, Issue 1
Clin IQ 5 (Contd.)
Preeclampsia is defined as hypertension (blood pressure >140/90)
and proteinuria (presence of at
least 0.3grams of protein in 24
hour period) observed during the
second half of pregnancy (>20
weeks gestation). Preeclampsia is
considered severe when any of the
following occur: blood pressure
above 160/110, thrombocytopenia, impaired liver function, renal
insufficiency, pulmonary edema or
cerebral or visual disturbances.
Preeclampsia, with or without
severe features, can evolve into
eclampsia with systemic complications and death. Once preeclampsia develops, the only effective
treatment is delivery.
Previous comprehensive systematic reviews and meta-analysis studies have suggested that prophylactic use of low-dose aspirin is associated with a significant reduction
in prevalence of severe preeclampsia, fetal growth restriction
and preterm birth. These are all
placenta-related complications of
pregnancy and although the exact
etiology of pre-eclampsia remains
unknown, it has been observed
that low-dose aspirin may improve
maternal and fetal outcomes. One
proposed mechanism is that aspirin inhibits thromboxane more
than prostacyclin production and
protects against vasoconstriction
and resulting pathological blood
coagulation in the placenta. Another proposed mechanism is based
on the concept that pre-eclampsia
is a consequence of impaired
trophoblastic invasion of maternal
spiral arteries. Low-dose aspirin
has been shown to cause improvement of uterine artery blood flow
resistance and therefore a greater
remodeling and transformation of
uterine spinal arteries. The spinal
arteries are usually completely
Page 8
developed by 16-18 weeks and
therefore the timing of aspirin
initiation has been suggested to be
a critical factor. Most previous
large randomized trials have only
evaluated the effect of aspirin
given in the second half of pregnancy and therefore further investigation into early initiation (<16
weeks gestation) of low-dose aspirin would be beneficial.
Summary of Evidence :
It has been suggested by metaanalyses of randomized studies
that prophylactic use of low-dose
aspirin initiated at or before week
16 of pregnancy is associated with
significant reduction in prevalence
of severe preeclampsia, fetal
growth restriction & preterm birth.
In one such meta-analysis, 42
studies including 27,222 women
who had risk factors for
preeclampsia were included.
These risk factors included: nulliparity, multiple pregnancy, chronic hypertension, cardiovascular or
endocrine disease, prior gestational hypertension or FGR, and/or
abnormal uterine artery Doppler.
All studies examined women who
initiated treatment at ≤16 weeks
of gestation and at >16 weeks of
gestation, and all included a control or placebo group. The outcome
of interest was perinatal mortality
defined as, fetal death after 16
week’ gestation or neonatal death
before 28 days of age. Secondary
outcomes included preeclampsia,
severe preeclampsia, FGR, preterm birth, placental abruption,
birth weight & gestational age at
delivery. When compared with
controls, low-dose aspirin started
at ≤16 weeks’ gestation compared
with low-dose aspirin started after
16 weeks’ gestation was associated with a greater reduction in
perinatal death (P = 0.02),
preeclampsia (P <0.01), severe
preeclampsia (P <0.01), FGR (P
<0.001) and preterm birth (P
<0.001). This is in agreement with
a second similar meta-analysis
which studied the effects of lowdose aspirin started in early pregnancy on incidence of preeclampsia and IUGR. In the second metaanalysis, pregnant women at moderate to high risk of preeclampsia
received either aspirin or placebo;
these were then analyzed by gestational age at initiation of either
aspirin or placebo (≤16 weeks or
16 weeks gestation). 34 randomized controlled trials were included
(11,348 women), 12 of those
being ≤16 weeks of gestation. Low
-dose aspirin initiated at ≤16
weeks was associated with a significant reduction in preeclampsia
(RR = 0.47) and IUGR (RR 0.44)
whereas aspirin started after 16
weeks was not. Low-dose aspirin
initiated ≤16 weeks was also associated with reduction in severe
preeclampsia (RR= 0.09), gestational hypertension (RR=0.62),
and preterm birth (RR=0.22).
Several weaknesses were of note
in these two articles. In the Roberge et al.4, the trials included
were not designed to evaluate
perinatal death, only a few trials
reported cause of studies, small
studies that showed no significant
effect were disregarded (funnel
pot) leading to possible publication
bias. In addition, the largest studies included in both articles recruited mostly women after 16 weeks
of gestation. Thus, the data is
limited in those for women ≤16
weeks of gestation as each study
individually was underpowered to
address perinatal death. With this
being said, more evidence needs
to be published on a larger population group of women ≤16 weeks of
gestation in order to change our
practice.
Conclusion:
In conclusion, preeclampsia is a leading cause of
maternal death and the prevalence
continues to rise. After review of
two large meta-analysis studies,
we can conclude that in pregnant
women, with increased risk for preeclampsia, low-dose aspirin initiated at <16 weeks (when compared
with initiation after 16 weeks) is
associated with reduction in severity of pre-eclampsia. However, due
to limitations and bias noted
above, further larger scale studies
are needed before we would
change our practice to initiate
Aspirin prior to 16 weeks gestation. Early identification of women
with risk factors for pre-eclampsia
will remain the first crucial step in
prevention of pre-eclampsia associated morbidity and mortality.
References:
1. Bujold E, Roberge S, Lacasse Y,
Bireau M, Audiert F, Marcoux S, et
al. Prevention of preeclampsia and
intrauterine growth restriction with
aspirin started in early pregnancy:
a meta-analysis. Obstet Gynecol.
2010;116:402-14.
2. Jillian, H. (2014). Low-Dose
Aspirin for Prevention of Morbidity
and Mortality From Preeclampsia:
A Systemic Evidence Review for
“Further larger scale
studies are needed before we
would change our practice
to initiate Aspirin prior to 16
weeks gestation.”
Clin IQ 2015
the U.S. Prevenive Services Task Force.
Annals of Internal Medicine, 160(10).
Retrieved January 4, 2015, from
www.annals.org
3. Repke, J. (2013). What is new in
Preeclampsia? Best Articles From the
Past Year. Obstetrics and Gynecology,
121(3).
4. Roberge, S, Nicolaides, K. H, Demers,
S, Villa P, and Bujold, E. Prevention of
perinatal death & adverse perinatal
outcome using low-dose aspirin: a metaanalysis. Ultrasound Obstet Gynecol
2013;41:491-499.
Clin IQ 6: In patients with nasal polyps, do systemic corticosteroids provide
equal or better efficacy than nasal corticosteroid therapy in treating
chronic viral rhino-sinusitis?
Authors: Inderjit Bolla, MD,
Anitha Kumaaravel, MD
Faculty Mentor: Priyanka Patnaik MD
May 2015.
There is a high recurrence rate of
disease in such patients. According to national surveys, chronic
rhino-sinusitis has been a significant chronic health condition affecting more than 31 million patients in the United States each
year2. Studies looking at initial
oral steroid therapy followed by
topical steroid therapy seem to
suggest greater effectiveness over
6 months than topical steroid
therapy alone in decreasing polyp
size and improving olfaction in
patients referred for specialty care
of chronic rhino-sinusitis with at
least moderate nasal polyposis
(CRSwNP).1
Inclusion Criteria : Presence on
Summary of the Evidence:
Residency Program: University
at Buffalo Family Medicine Buffalo
General/ Jefferson Track
Answer: Yes. An initial 2 weeks
5. Robert, G., & Michel, A. (2008). Does
low-dose aspirin reduce preeclampsia
and other maternal-fetal complications?
The Journal of Family Practice, 57(1),
54-56.
of oral prednisolone therapy significantly improves polyp size and
olfaction in those with Chronic
rhino-sinusitis with nasal polyposis
(CRSwNP).
Special thanks to Adrienne Doeppe,
Librarian at MFS who found these articles via OVID database search.
Level of Evidence : A
Search Terms: Chronic rhinosinusitis, corticosteroid therapy,
nasal polyposis.
Date Search was Conducted:
“An initial 2 weeks of oral
prednisolone therapy
significantly improves
polyp size and olfaction in
those with Chronic rhinosinusitis with nasal
polyposis”
nasoendoscopy of bilateral moderate-sized to large nasal polyps
according to the Lildholdt scale
and at least 2 of anterior or posterior nasal discharge, nasal obstruction, or decreased sense of smell
for more than 12 weeks.
Exclusion Criteria: Treatment
with an oral corticosteroid in the
past 3 months, sinus surgery in the
past year, recent upper respiratory
tract infection, mechanical nasal
airway obstruction of more than
50% due to septal deviation, or
pregnancy or lactation.
Summary of Issues:
Chronic rhino-sinusitis accounts for
substantial health care expenditures including office visits, antibiotic prescriptions filled, missed
Page 9
work and school days 2. Approximately 20% of patients with chronic rhino-sinusitis have nasal polyposis, which is a common indication for nasal surgery .2
In 2013, a comprehensive systematic review was done of 30 studies
with chronic rhino-sinusitis without
polyposis (CRSsNP) and 3 studies
on allergic fungal sinusitis 3. Two
retrospective and one prospective
study used oral steroids in combination with antibiotics and nasal
steroids. The systematic evaluation was done of oral steroid use in
CRSwNP, which has not been
previously conducted. The objective of this study was to assess
evidence on oral steroid therapy in
CRSwNP via a literature review. A
potential downside to this review is
that the authors did not include
any randomized control trials or
any clinical study that employed
oral systemic corticosteroids alone
and in those with Chronic Rhinosinusitis with nasal polyps
(CRSwNP) 3.
A 2011 trial assessed treating
chronic rhino-sinusitis with nasal
polyposis (CRSwNP) with oral steroids followed by topical steroids.
This Parallel randomized trial studied 60 adults with CRSwNP
(moderate to large sized polyps)
who were referred by primary
physicians for specialty care 1. The
mean decrease in polyp grade
from baseline to 2 weeks was 2.1
units (SD, 1.1) in the prednisolone
group and 0.1 unit (SD, 1.0) in the
placebo group (mean difference
between groups, -1.8 units [95%
CI, -2.4 to -1.2 units]; P < 0.001) 1.
Patients were randomly assigned
in a 1:1 ratio to receive oral prednisolone, 25 mg/d, or placebo for 2
weeks, followed in both groups by
fluticasone propionate nasal
drops, 400 µg twice daily, for 8
weeks followed by fluticasone
propionate nasal spray, 200 µg
twice daily, for 18 weeks 1. Initial
oral steroid therapy followed by
topical steroid therapy seems to
be more effective over 6 months
than topical steroid therapy alone
in decreasing polyp size and improving olfaction in patients referred for specialty care of chronic
rhino-sinusitis with at least moderate nasal polyposis 1. A possible
limitation here may be that patients were referred from primary
care to a single-center rhinology
clinic, which limits the generalizability of results 1. Serial measurements of surrogates of nasal inflammation (such as nitric oxide or
cytokine levels) were not performed 1.
Conclusion:
Based on our research in literature, we concluded that in patients
with CRS with nasal polyposis an .
Volume 1, Issue 1
Clin IQ 6 (Contd.)
initial 2-week coarse of oral prednisolone in a single once daily
dose of 25mg can significantly
improve polyp size and reduce the
burden of symptoms as well as
prevent the high relapse rates
seen in this population 1This study
provides clear strong evidence to
guide practitioners on initiation of
maintenance therapy in such patients with CRSwNP, a condition
Page 10
that caries a high prevalence rate
and significant morbidity in our
community.
References:
1. Vaidyanathan S, Barnes M,
Williamson P, Hopkinson P, Donnan P, Lipworth, B. Treatment of
chronic rhino-sinusitis with nasal
polyposis with oral steroids followed by topical steroids: a ran-
domized trial. Annals Intern Med.
2011;154(5):293-302.
2. Hamilos DL. Chronic Rhinosinusitis: Epidemiology and medical management. Journal of Allergy and Clinical Immunology. 2011
Oct;128(4):693-707.
3. Poetker DM, Lakubowksi LA, Lal
D, Hwang PH, Wright ED, Smith TL.
Oral Corticosteroids in the management
of adult chronic rhino-sinusitis with and
without nasal polyps; an evidence-based
review with recommendations. International Forum Allergy and Rhinology.
2013 Feb;3(2):104-20.