Sunday, January 25, 2015

First Independence war of India and it's Antecedents.

I always  wondered about the  first  independence war of India  and  it's antecedents.
this was called the  sepoy mutiny by the  british.

the spark which lit the fire  was  supposedly the  rumor that  the cartridges  for the  bullets were coated with  pig and  cow  fat  which  were  religiously forbidden  for  muslims and hindus respectively.

Not  knowing  why  a metal cased  cartridge/bullet is neede to be  dipped in  fat ( knowing  only about  modern  weapon ) I  always  wondered  .
recently  I came  across this   from  a  wordpress  personal  webpage  of  a sinhala enthusiast who gave  detailed  descriptions  of   flintlock and  match lock  weapons  which  were  the   weapons  used  by  the  british  army  before  the  modern  weapons  and   now  it makes  sense  .

as the  cartridges  were  just  twisted  paper containing  gun powder  and  the  lead  ball . the  fat  was  used to make  them  water  proof .

and  the  drill  included  a step  where  the  soldier  had  to  tear the  cartridge  using  his  teeth to load the  gun.


An English Civil War manual of the New Model Army showing a part of the steps required to load and fire an earlier musket. The need to complete this difficult and potentially dangerous process as quickly as possible led to the creation of the military drill.[19]
In the 18th century, as typified by the English Brown Bess musket, loading and firing was done in the following way:
• Upon the command “prime and load”, the soldier would make a quarter turn to the right at the same time bringing the musket to the priming position. The pan would be open following the discharge of the previous shot, meaning that the frizzen would be tilted forward. If the musket was not being reloaded after a previous shot, the soldiers would be ordered to “Open Pan”.
• Upon the command “Handle cartridge”, the soldier would draw a cartridge from the cartridge box worn on the soldier’s right hip or on a belt in front of the soldier’s belly. Cartridges consisted of a spherical lead ball wrapped in a paper cartridge which also held the gunpowder propellant. The end of the cartridge opposite from the ball would be sealed by a mere twist of the paper. The soldier then tore off the twisted end of the cartridge with the teeth and spat it out, and continued to hold the now open cartridge in his right hand.
• Upon the command “prime”, the soldier then pulled the hammer back to half-cock, and poured a small amount of powder from the cartridge into the priming pan. He then closed the frizzen so that the priming powder was trapped.
• Upon the command “about”, the butt of the musket was then lowered and moved to a position against the soldier’s left calf, and held so that the soldier could then access the muzzle of the musket barrel. The soldier then poured the rest of the powder from the cartridge down the muzzle. The cartridge was then reversed, and the end of the cartridge holding the musket ball was inserted into the muzzle, with the remaining paper shoved into the muzzle above the musket ball. This paper acted as wadding to stop the ball and powder from falling out if the muzzle was lowered.
• Upon the command “draw ramrods”, the soldier drew the ramrod from the musket. The ramrod was grasped and reversed when removed, and the large end was inserted about one inch into the muzzle.
• Upon the command “ram down cartridge”, the soldier then used the ramrod to firmly ram the wadding, bullet, and powder down to the breech of the barrel. The ramrod was then removed, reversed, and returned to half way in the musket by inserting it into the first and second ramrod pipes. The soldier’s hand then grasped the top of the ramrod.
• Upon the command “return rammers”, the soldier would quickly push the rammer the remaining amount to completely return it to its normal position. Once the ramrod was properly replaced, the soldier’s right arm would be held parallel to the ground at shoulder level, with the right fingertips touching the bayonet lug, and lightly pressing the musket to the soldier’s left shoulder. The soldier’s left hand still supported the musket.
(At no time did the soldier place the musket on the ground to load)
• Upon the command “Make Ready”. The musket was brought straight up, perpendicular to the ground, with the left hand on the swell of the musket stock, the lock turned toward the soldier’s face, and the soldier’s right hand pulled the lock to full cock, and grasped the wrist of the musket.
• Upon the command “present”, the butt of the musket was brought to the soldier’s right shoulder, while at the same time the soldier lowered the muzzle to firing position, parallel to the ground, and sighting (if the soldier had been trained to fire at “marks”) along the barrel at the enemy.
• Upon the command of “fire”, the soldier pulled the trigger, and the musket (hopefully) fired. A full second was allowed to pass, and the musket was then quickly lowered to the loading position, butt against the soldier’s right hip, muzzle held off center to the left at about a forty-five degree angle, and the soldier would look down at his open pan to determine if the prime had been ignited.
This process was drilled into troops until they could complete the procedure upon hearing a single command of “prime and load”. No additional verbal orders were given until the musket was loaded, and the option was either to give the soldiers the command “Make Ready”, or to hold the musket for movement with the command of “Shoulder your firelock”. The main advantage of the British Army was that the infantry soldier trained at this procedure almost every day. A properly trained group of regular infantry soldiers was able to load and fire four rounds per minute. A crack infantry company could load and fire five rounds in a minute."

146 MEDICAL PROCEDURES WHICH ARE NO LONGER RECOMMENDED.

Article Date of
Publication
How it contradicted existing medical practice?
1
Vaccinations and the
Risk of Relapse in
Multiple Sclerosis
2/1/01 Longstanding concerns about vaccinations
preceding the onset or relapses of multiple
sclerosis have led to clinician reluctance to give
vaccinations to these patients 1. In this
observational, multicenter, case-crossover study in
patients with multiple sclerosis, there was no
increased risk of relapse in the two-month period
immediately following tetanus, hepatitis B or
influenza vaccination.
2
Hepatitis B
Vaccination and the
Risk of Multiple
Sclerosis
2/1/01
Several cases of multiple sclerosis developing
within weeks after receiving a new hepatitis B
vaccination raised safety concerns about the
vaccination, eventually leading to the French
governmentʼs suspension of a school-based
hepatitis B vaccination program 2, 3. In a nested
case-control study of two large cohorts of nurses,
no association was found between receiving the
hepatitis B vaccination and the development of
multiple sclerosis.
3 Lack of Effect of
Induction of
Hypothermia after
Acute Brain Injury
2/22/01 Since the 1930s, small studies and laboratory
investigations have suggested that hypothermia
after acute brain injury is an effective therapy4.
Although these data were not strong, many
centers began to cool patients routinely despite
the effort this required4. This prospective,
multicenter, randomized controlled trial found no
benefit for such cooling, contradicting a decades
old practice.
4
Initial Plasma HIV-1
RNA Levels and
Progression to AIDS
in Women and Men
3/8/01
The initial viral load after seroconversion in men
with HIV-1 predicts the progression to AIDS 5, 6,
although it is unclear if this is also true in women.
Current guidelines recommend initiating
antiretroviral therapy based on viral load in both
women and men 7. This study found that although
the initial HIV-1 viral load was lower in women,
rates of progression to AIDS was similar and that
guidelines based on viral load rather than CD4
count leads to treatment differences based on sex.
5
The Teratogenicity of
Anticonvulsant Drugs
4/12/01
Two medical textbooks and one review article8
have doubted that anticonvusants taken during
pregnancy are more teratogenic than epilepsy
itself. This9 large observational study found that
contrary to this position, a systematic examination
of infants reveals anticonvulsants during
pregnancy increase the risk of fetal malformation.
6
Effect of Early or
Delayed Insertion of
4/19/01
Current guidelines recommend insertion of
tympanostomy tubes in children with otitis media
with effusion of greater than three months
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2
Tympanostomy tubes
for Persistent Otitis
Media on
Developmental
Outcomes at the Age
of
Three Years
duration, due to concerns of associated
conductive hearing loss leading to developmental
impairments 10. This randomized study did not
find any difference in developmental outcomes in
children 3 years old or younger with otitis media
with effusion that had prompt tympanostomy tube
placement versus delayed placement up to 9
months later if effusion persisted.
7
The Effect of
Chelation Therapy
with Succimer on
Neuropsychological
Development in
Children Exposed to
Lead
5/10/01 Although oral lead chelation therapy with succimer
had been implemented, its effect on preventing
cognitive impairments in children with moderately
elevated blood lead levels is unknown 11. This
randomized, placebo-controlled trial did not find a
significant difference in cognitive or behavioral
outcomes in children with moderately elevated
blood levels treated with succimer.
8 Long-Term Effects of
Indomethacin
Prophylaxis in
Extremely-Low-Birth-
Weight Infants
6/28/01
Prophylactic indomethacin treatment in extremelylow-
birth-weight infants reduces the frequency of
patent ductus arteriosus and severe
intraventricular hemorrhage 12, although little is
known about the long-term effects of this
treatment. This randomized, placebo-controlled
trial showed that extremely-low-birth-weight infants
receiving this treatment did not have any
improvements in survival without neurosensory
impairment at 18 months.
9
Two Controlled Trials
of Antibiotic
Treatment in Patients
with Persistent
Symptoms and a
History of Lyme
Disease
7/12/01 Many patients with persistent symptoms of Lyme
disease receive prolonged courses of antibiotics,
although the effectiveness of this practice remains
unknown 13. This randomized, placebo-controlled,
double-blinded trial failed to show any significant
improvement in symptoms after a prolonged 90-
day course of antibiotics in patients with persistent
symptoms.
10 Three Months versus
One Year of Oral
Anticoagulant
Therapy for
Idiopathic Deep
Venous Thrombosis
7/19/01
Studies have shown that treatment for an
idiopathic deep venous thrombosis (DVT) with oral
anticoagulation therapy for greater than three
months reduces the risk of recurrent DVT while on
therapy, although it is unclear if this benefit
continues once anticoagulation is stopped 14. This
multicenter, randomized trial showed that a
prolonged course of oral anticoagulation following
an idiopathic DVT delayed but did not reduce the
long-term risk for a recurrent DVT when compared
to a three-month course of treatment.
11
Failure of
Metronidazole to
Prevent Preterm
Delivery among
Pregnant Women
with Asymptomatic
8/16/01
Recommendations have been made for the
screening and treatment of asymptomatic
Trichomonas vaginalis infections in pregnant
women in order to prevent low birth weight and
preterm birth 15. In this randomized trial, treatment
of asymptomatic Trichomonas with metronidazole
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3
Trichomonas
vaginalis Infection
during pregnancy was actually significantly
associated with an increase risk of preterm birth.
12
Effect of Prone
Positioning on the
Survival of Patients
with Acute
Respiratory Failure
8/23/01 Prone positioning in ventilated patients with acute
lung injury or acute respiratory distress syndrome
improves oxygenation and has been increasingly
utilized 16. However, this multicenter, randomized
trial failed to show any survival benefit of the prone
position compared to the supine position in
ventilated patients with these conditions.
13 Medical Treatment
for
Neurocysticercosis
Characterized by
Giant Subarachnoid
Cysts
9/20/01
Surgery is considered the treatment of choice for
the helminthic infection neurocysticercosis when it
is associated with giant cysts and intracranial
hypertension 17. In this series of patients with
neurocysticercosis with giant cysts and intracranial
hypertension, intensive medical therapy with
corticosteroids and the antihelminthic drugs
albendazole and praziquantal resulted in clinical
improvement in all patients, suggesting that
surgery may not be needed in all such patients.
14 Naltrexone in the
Treatment of Alcohol
Dependence
12/13/01
Naltrexone is an opioid-receptor antagonist that is
FDA-approved for the treatment of alcohol
dependence, although its efficacy is uncertain 18,
19. In this multicenter, double-blind, placebocontrolled
study, naltrexone used as an adjunct to
standardized psychosocial treatment failed to have
any significant effect on the treatment of alcohol
dependence.
15 Comparison of Two
Diets for the
Prevention of
Recurrent Stones in
Idiopathic
Hypercalciuria
1/10/02 A low-calcium diet is widely recommended for
patients with a history of kidney stones and
idiopathic hypercalcuria20. Theoretically, this
would lower the concentration of calcium in the
urine, prevent supersaturation, and decrease
stone formation. This trial21 randomized such
patients to a low-calcium diet or a diet low in
animal protein and salt (but with normal calcium).
At 5 years they found nearly double the risk of
recurrence in the low-calcium diet group.
16 Frequency of Uterine
Contractions and the
Risk of Spontaneous
Preterm Delivery
1/24/02 Ambulatory monitoring of uterine contractions
continues in the United States despite evidence
suggesting it does not improve the rate of preterm
delivery22. This observational study formally
assessed the test characteristics of frequent
contractions in predicting early delivery found no
threshold had good sensitivity and reasonable
positive predictive value, further undermining
ongoing practice.
17 Screening of Infants
and Mortality Due to
Neuroblastoma
4/04/02 Mass screening of infants for neuroblastoma had
been done as part of pilot studies in the U.K.,
France, Austria, Australia, U.S.A., Italy, Norway
and Germany23. In Japan, screening was
instituted in the 1970s, with over 7 million children
undergoing screening, and 650 cases of
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4
neuroblastoma found by the 1990s23. This large
population study of 476,654 children in Canada
found this practice did not decrease mortality from
neuroblastoma.24 The study also makes us
question another handful of newborn and infant
screening, which remains untested25.
18 Neuroblastoma
Screening at One
Year of Age
4/04/02
Mass screening of infants for neuroblastoma had
been done as part of pilot studies in the U.K.,
France, Austria, Australia, U.S.A., Italy, Norway
and Germany23. In Japan, screening was
instituted in the 1970s, with over 7 million children
undergoing screening, and 650 cases of
neuroblastoma found by the 1990s23. This large
population study of 2.5 million children in Germany
found this practice did not decrease mortality from
neuroblastoma.26
19 Immediate Repair
Compared with
Surveillance of Small
Abdominal Aortic
Aneurysms
5/09/02 For over a decade, vascular surgery societies had
recommended elective repair of aneurysms of 4.0
cm or more in diameter for patients without
medical contraindications27. This randomized trial
examined patients with aneurysms between 4.0
and 5.4 cm in diameter. It found no improvement
in mortality for this procedure compared to
observation, even though elective operative
mortality was low28.
20 Intranasal Mupirocin
to Prevent
Postoperative
Staphylococcus
aureus Infections
6/13/02 Patients who carry Staph Aureus in their nasal
passages are more likely to have surgical site
infections, often with the same isolate they are
colozied with. Several previous studies29, 30
showed that intranasal mupirocin can decrease
the rate of surgical site infection among such
patients compared to historical controls. This
randomized control trial31 however, found that the
prophylactic intranasal application of mupirocin did
not significantly reduce the rate of Staph Aureus
surgical-site infections.
21 A Controlled Trial of
Arthroscopic Surgery
for Osteoarthritis of
the Knee
7/11/02 650,000 arthroscopic knee surgeries were
performed annually in the US at a cost of $5000
dollars each at the time of this randomized trial.32
This study found that the intervention performed
no better than a placebo intervention on the
outcome of pain and function.
22 Twenty-Five-Year
Follow-up of a
Randomized Trial
Comparing Radical
Mastectomy, Total
Mastectomy, and
Total Mastectomy
Followed by
Irradiation
8/22/02 Radical Halsted Mastectomy (RHM) rose to
prominence without randomized controlled trials
supporting its efficacy. This 25 year follow-up of a
large randomized study33 comparing RHM to
mastectomy with radiation, or mastectomy with
sentinel node dissection and axillary node removal
only if positive found that less aggressive surgical
techniques had similar mortality outcomes. Thus,
the trial failed to show benefit for a more
aggressive surgery, which dominated medicine in
the 20th century
23 Sex-Based 10/31/02 In 1997, a randomized trial found that digitalis
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5
Differences in the
Effect of Digoxin for
the Treatment of
Heart Failure
decreased the rate of hospitalization for patients
with heart failure with no adverse (or beneficial)
effect on mortality34. Because of these results, the
American College of Cardiology35, European
Society of Cardiology36, and the Heart Failure
Society of America37 all recommend this
medication for all patients. However, whether the
effect differs in men and women was unknown.
This analysis38 found that digitalis increases the
rate of death among women.
24 Antimicrobial
Treatment in Diabetic
Women with
Asymptomatic
Bacteriuria
11/14/02 In contrast to Europe, in the United States, several
groups39, 40 recommended screening and treating
asymptomatic bacteriuria among women with
diabetes. This randomized trial found although
this practice leads to more antibiotic use, it did not
reduce complications or improve the time to
symptomatic infection.
25 A Comparison of
Rate Control and
Rhythm Control in
Patients with Atrial
Fibrillation
12/5/02 Many physicians treat patients with atrial fibrillation
with costly anti-arrhythmic drugs in a strategy to
maintain sinus rhythm. While this approach has a
physiologic rationale, and improves some
surrogate endpoints, it has not been proven to
improve survival. The AFFIRM study41 showed
that a strategy of rate control yielded similar
mortality outcomes, and fewer adverse drug
reactions.
26 A Comparison of
Rate Control and
Rhythm Control in
Patients with
Recurrent Persistent
Atrial Fibrillation
12/5/02 For many patients with atrial fibrillation,
management strategies focus on maintaining
sinus rhythm, often with repeat electric
cardioversion and prophylactic anti-arrhythmic
drugs42. This study43 found no benefit with respect
to mortality for a rhythm as opposed to rate control
strategy.
27 A Randomized,
Controlled Trial of the
Use of Pulmonary-
Artery Catheters in
High-Risk Surgical
Patients
1/2/03 The pulmonary artery catheter (PAC) is frequently
used for hemodynamic monitoring in the intensive
care unit. There has not been a definitive
randomized controlled trial to evaluate the clinical
value of this monitoring device. At the time of this
article, more than 1.5 million PACs were placed in
North America annually44. This study evaluated
this claim through 3803 patients randomized to
surgery with PAC vs. surgery without if ICU stay
was anticipated. There was no benefit to therapy
directed by PAC over standard care in elderly,
high-risk patients post operatively.
28 Imaging Studies after
a First Febrile Urinary
Tract Infection in
Young Children
1/16/03 In children between the ages of 2 and 24 months
who present with a UTI, the American Association
of Pediatrics recommends a voiding
cystourethrogram and renal ultrasound45. This
study evaluated this practice in a prospective
cohort. It sought to determine whether imaging
studies altered management or improved
outcomes in children with a first febrile urinary
tract infection. This study found that an ultrasound
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6
in this clinical setting is almost always normal
(88%), and if abnormal, clinical management was
unchanged (Reversal) If voiding cystouretrogra
was abnormal, non-evidence based strategies
were offered (thus no conclusion can be drawn)
29 Serum Retinol Levels
and the Risk of
Fracture
1/23/03 Many nations fortify foods with Vitamin A in hopes
of preventing Vitamin A deficiency, which is rare
and associated with night blindness
xerophthalmia and keratomalacia46. In Sweden,
margarine and other dairy products are fortified47
This study sought to determine whether there is an
elevated fracture risk in patients with elevated
vitamin A levels. This study found that the risk of
fracture was highest among men with the highest
levels of serum retinol (a marker of vitamin A
ingestion). This suggests that the current practice
of Vitamin A supplementation and food fortification
ought be re-evaluated.
30 Factors Associated
with Progression of
Carcinoid Heart
Disease
3/13/03 One of the treatments currently being used for
metastatic midgut carcinoid tumors are cytotoxic
chemotherapeutic agents. The data supporting
this intervention is dubious48, 49. The current
retrospective investigation50 found cytotoxic
agents to be a strong risk factor for carcinoid heart
disease, despite reduction in 5-HIAA in many
patients. Thus, an intervention of dubious efficacy
is found to potentially have a significant harm.
31 Effects of Estrogen
plus Progestin on
Health-Related
Quality of Life
5/8/03 Hormone replacement therapy with estrogen and
progestin has been reported to improve vasomotor
symptoms51, 52. As such, these hormones have
been used by women to improve quality of life
after menopause53, 54. This Womenʼs Health
Initiative study evaluated the use of estrogen plus
progestin on quality of life. There was no
significant effect on health, vitality, mental health,
depressive symptoms or sexual satisfaction in the
hormone arm as compared to placebo.
32 Involved-Field
Radiotherapy for
Advanced Hodgkin's
Lymphoma
6/12/03 Despite dramatic changes in the management of
Advanced Hodgkinʼs disease over the last 2
decades, many physicians continue to treat these
patients with radiation therapy. They cite data that
shows it decreases local recurrence55. Even free
and overall survival were not significantly different,
and, if anything, favored the omission of
radiotherapy.
33 Conventional
Adjuvant
Chemotherapy with
or without High-Dose
Chemotherapy and
Autologous Stem-Cell
Transplantation in
High-Risk Breast
Cancer
7/3/03 Multiple studies have claimed that high dose
chemotherapy with stem cell transplantation
improves disease free survival at 3 years to 65-
70%, an improvement of 20-30% beyond standard
adjuvant chemotherapy56, 57. High dose chemo
and stem cell transplant became a common, costly
and controversial practice for more than a decade.
This trial randomized patients with primary breast
cancer with at least 10 ipsilateral axillary lymph
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7
nodes to standard adjuvant chemotherapy vs.
adjuvant chemotherapy followed by high dose
chemotherapy and stem cell transplantation. The
study arm was found to reduce risk of relapse but
no improvement in survival was found.
34 A Multicenter,
Randomized, Double-
Blind, Controlled Trial
of Nebulized
Epinephrine in
Infants with Acute
Bronchiolitis
7/3/03 Multiple studies have demonstrated improved
short-term outcomes after epinephrine
administration in infants with acute bronchiolitis58-
60 . This randomized, double blind trial compared
nebulized epinephrine with placebo in 194 infants
with bronchiolitis. There was no significant
difference in length of hospitalization, a more
meaningful endpoint, between the groups
35 Evaluation of
Impermeable Covers
for Bedding in
Patients with Allergic
Rhinitis
7/17/03 The encasement of bedding with impermeable
covers has been recommended for the treatment
of allergic rhinitis61, 62. These recommendations
are part of an effort to reduce exposure to housedust
mites. This study evaluated this
recommendation by randomly assigning 279
patients with allergic rhinitis to impermeable vs.
permeable bedding covers. There was a reduction
in allergen emission from mattresses in the
impermeable group but no effect on clinical
outcomes.
36 Control of Exposure
to Mite Allergen and
Allergen-
Impermeable Bed
Covers for Adults
with Asthma
7/17/03 The cost of impermeable bed covers is in the
millions of dollars annually, while the cost of all
preventive interventions for asthma and allergic
rhinitis is in the billions63. US64 and European65
guidelines recommend these covers be used
among many patients with asthma. This doubleblind,
randomized, placebo-controlled trial of over
1100 patients found no benefit on any clinical or
physiologic outcome for this practice.
37 Estrogen plus
Progestin and the
Risk of Coronary
Heart Disease
8/7/03 Observational studies suggested that postmenopausal
hormonal replacement would
decrease coronary artery disease66. This study
randomized postmenopausal women to either
estrogen/progesterone vs. placebo to evaluate this
claim. After a 5.2 year follow up, no cardiac
protection was found and CHD risk was potentially
elevated in the first year of use.
38
Hormone Therapy
and the Progression
of Coronary-Artery
Atherosclerosis in
Postmenopausal
Women
8/7/03 Observational studies suggested that postmenopausal
hormonal replacement would
decrease coronary artery disease66. This study
found that these medications do not slow the
progression of coronary artery disease.
39 Outcomes at School
Age after Postnatal
Dexamethasone
Therapy for Lung
Disease of
Prematurity
3/25/04
Postnatal dexamethasone has long been practiced
to prevent or treat chronic lung disease in
premature newborns67, but the long-term
developmental side effects are unknown. This
double-blind, placebo-controlled trial of early
postnatal dexamethasone therapy (within 12 hours
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8
of birth) showed that this therapy led to
significantly more delays in somatic growth (head
circumference and height), poorer neuromotor and
cognitive function (including IQ scores) and more
clinically significant disabilities when the children
became of school-age.
40 C-Reactive Protein
and Other Circulating
Markers of
Inflammation in the
Prediction of
Coronary Heart
Disease
4/1/04
Measuring C-reactive protein (CRP) to evaluate for
the risk of coronary atherosclerosis has been
supported by 2003 consensus statements from the
Centers for Disease Control and Prevention and
the American Heart Association68. A prospective
cohort study from patients in Reykjavik, Iceland
showed that CRP was only a relatively moderate
predictor of the risk of coronary artery disease and
added only marginally to the predictive value of
established risk factors. The authors called for the
recent recommendations from the CDC and AHA
to be reviewed on the basis of their findings.
41 The Influence of
Resection and
Aneuploidy on
Mortality in Oral
Leukoplakia
4/1/04
THIS PAPER WAS ITSELF RETRACTED IN
NEJM 2006 b/c of possible falsified data
42
A Comparison of
High-Dose and
Standard-Dose
Epinephrine in
Children with Cardiac
Arrest
4/22/04
The American Heart Association 2000 guidelines
for pediatric advanced life support recommended
that rescue doses of epinephrine (i.e. those
subsequent to the initial dose) during
cardiopulmonary resuscitation be at the standard
dose (0.01 mg per kg of body weight) or a higher
dose (0.1 mg per kg)69. In this prospective,
randomized, double-blind trial that compared high
dose to standard dose epinephrine for rescue
therapy, there was no benefit of high dose therapy
in the rate of return of spontaneous circulation for
in-hospital cardiac arrests. High dose epinephrine
also led to a lower rate of survival within 24 hours
and a lower rate of survival to hospital discharge
as compared to the standard dose.
43 Open Mesh versus
Laparoscopic Mesh
Repair of Inguinal
Hernia
4/29/04
A laparoscopic approach to repair inguinal hernias
with mesh was thought to have lower hernia
recurrence rates and less post-operative pain70, 71.
This multicenter, randomized trial in a VA
population found that the laparoscopic approach
led to a higher rate of complications and a higher
rate of recurrences when repairing primary
inguinal hernias.
44 Folate Therapy and
In-Stent Restenosis
after Coronary
6/24/04
Previous studies72, 73 have suggested that folate
therapy (folic acid, Vitamin B6, and Vitamin B12)
reduce homocysteine levels which thereby lower
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9
Stenting
the rate of coronary atherosclerosis. One such
clinical study72 found that folate therapy reduced
the rate of restenosis after coronary angioplasty
which led some interventionalists to adopt the use
of this therapy. This double-blind, placebocontrolled
randomized trial conducted in Germany
and the Netherlands showed that contrary to
previous findings, folate therapy actually increased
the restenosis rate and increased the need for
repeat revascularization after a coronary
intervention was performed.
45 Methylprednisolone,
Valacyclovir, or the
Combination for
Vestibular Neuritis
7/22/04
The etiology of vestibular neuritis is presumed to
be a viral infection74 and yet it is unknown whether
steroids, an anti-viral or a combination of both
have any benefit in treating this disease. At the
time of this publication, physicians prescribed
either or both. A prospective, randomized, doubleblind,
two-by-two factorial trial was performed
assessing whether placebo, methylprednisolone,
valacyclovir or a combination of the two would
improve symptoms. Only the steroid and not the
anti-viral improved the recovery of patients with
vestibular neuritis.
46 Lumpectomy plus
Tamoxifen with or
without Irradiation in
Women 70 Years of
Age or Older with
Early Breast Cancer
9/2/04
Several breast cancer trials have shown that postoperative
irradiation decreases the rate of
ipsilateral recurrence but does not affect rate of
survival75, 76 yet was still being used in clinical
practice. Women over the age of 70 years old with
estrogen receptor positive breast cancer in this
randomized study received no benefit with
lumpectomy plus tamoxifen and irradiation
compared to lumpectomy plus tamoxifen alone, as
the five year survival rates and rates of distant
metastes were no different in the two groups.
47 Fresh Whole Blood
versus Reconstituted
Blood for Pump
Priming in Heart
Surgery in Infants
10/14/04
In an attempt to decrease the coagulapathic and
inflammatory changes seen during cardiopulmonary
bypass surgery, pediatric
cardiothoracic surgeons have opted to use fresh
whole blood during congenital heart operations for
their neonate and infant patients77, 78, thus
becoming the standard of care. However, this
single-centered, randomized, double-blind
controlled trial showed that fresh whole blood had
no advantage over reconstituted blood (i.e.
combination of packed red cells and fresh-frozen
plasma) during surgery for this pediatric
population. Additionally, the use of whole blood led
to increased ICU length of stay and increased
post-operative fluid overload.
48 Angiotensin-
Converting–Enzyme
11/11/04
For patients with vascular disease, but without HF,
the HOPE79 and EUROPA80 trials suggested a
!"#$%&'$"()"*$+$,-&."
10
Inhibition in Stable
Coronary Artery
Disease
benefit of ace-inhibitors. Because of these
studies, many physicians began prescribing aceinhibitors
widely for patients with vascular
disease—beyond the inclusion criteria of these
studies, or utilizing different medications in the
same class81. The Prevention of Events with
Angiotensin Converting Enzyme Inhibition
(PEACE) trial demonstrated that patients with
stable coronary artery disease and preserved left
ventricular function who are already on current
standard therapy do not benefit with the addition of
trandolapril. In this low risk population, the
addition of an ACE-inhibitor did not reduce rates of
cardiovascular death, myocardial infarction or
coronary revascularization.
49 Secondary Surgical
Cytoreduction for
Advanced Ovarian
Carcinoma
12/9/04
Several prospective studies and one randomized
trial82 have shown that for women with advanced
ovarian carcinoma who were treated with primary
cytoreductive surgery and chemotherapy, but who
were subsequently found to have recurrent
disease, secondary surgical cytoreduction,
improves progression-free and overall survival.
However, in the prior RCT, not all patients
underwent a primary maximal debulking surgery.
Thus, in clinical practice, patients who were
previously maximally debulked, and treated with
chemo, were being debulked again. This
randomized trial found that secondary surgical
cytoreduction after chemotherapy did not improve
progression-free survival or overall survival rates
compared to chemotherapy alone in those whose
primary debulking surgery was maximal.
50 Coronary-Artery
Revascularization
before Elective Major
Vascular Surgery
12/30/04
Many clinicians perform routine coronary-artery
revascularization prior to vascular surgery in order
to improve preoperative risk in patients with stable
disease, even deviating from published
guidelines83. This randomized, multicentered VA
trial revealed that coronary artery revascularization
in patients with stable disease before undergoing
elective vascular surgery did not offer any benefit.
51 Mild Intraoperative
Hypothermia during
Surgery for
Intracranial
Aneurysm
1/13/05 Hypothermia was found to be helpful as a
neurosurgical adjunct in 1955, especially for
ischemic and traumatic insults. At the time of this
publication, it was being used in nearly 50% of
aneurysm surgeries84. This large randomized
study, the Intraoperative Hypothermia for
Aneurysm Surgery Trial (IHAST), showed no
improvement in neurologic outcomes with
hypothermia, and an increase in bacterial
infections.
52 Clopidogrel versus 1/20/05 Joint American College of Cardiology and
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11
Aspirin and
Esomeprazole to
Prevent Recurrent
Ulcer Bleeding
American Heart Association guidelines
recommended that patients who have had GI
bleeding while on aspirin consider the use of
clopidogrel or the addition of a PPI85. While the
guidelines treat both as equivalent strategies, this
study showed that aspirin plus esomeprazole was
far superior to clopidogrel in preventing future
ulcer bleeding.
53 The Risk of Cesarean
Delivery with
Neuraxial Analgesia
Given Early versus
Late in Labor
2/17/05 The American College of Obstetrics and
Gynecology recommends that epidural anesthesia
be delayed until cervical dilation has reached at
least 4cm. In the interm, patients are encouraged
to use and systemic opioids86. This
recommendation is based on a small randomized
trial87, and a post-hoc analysis of a larger one88
that found an increased risk of cesection with early
epidural anesthesia. The current study showed no
difference in the risk of cesarean delivery between
the two forms of anesthesia.
54 UK Controlled Trial of
Intrapleural
Streptokinase for
Pleural Infection
3/3/05 Management guidelines89 suggest that intrapleural
fibrinolytics help the drainage of infected pleural
effusions and reduce the need for surgical
drainage. This study, the First Multicenter
Intrapleural Sepsis Trial (MIST1), found no benefit
in mortality, need for surgery, or length of hospital
stay with intrapleural streptokinase.
55 Cardiovascular
Events Associated
with Rofecoxib in a
Colorectal Adenoma
Chemoprevention
Trial
3/17/05 Selective COX-2 inhibitors were widely prescribed
in lieu of NSAIDs because they demonstrated
similar analgesic levels with fewer GI side
effects90. In addition, COX-2 was identified as a
promoter of intestinal tumorigenesis and selective
COX-2 inhibition was believed to have the
potential to prevent colorectal adenomas91. The
first study noted here, the Adenomatous Polyp
Prevention on Vioxx (APPROVE) Trial, showed an
increase in cardiovascular risk with rofecoxib.
56 Cardiovascular Risk
Associated with
Celecoxib in a
Clinical Trial for
Colorectal Adenoma
Prevention
3/17/05 The second study, the Adenoma Prevention with
Celecoxib (APC) Study, showed a dose-response
association with celecoxib use and cardiovascular
risk.2
57 Complications of the
COX-2 Inhibitors
Parecoxib and
Valdecoxib after
Cardiac Surgery
3/17/05 Selective COX-2 inhibition was previously shown
to reduce the need for opioids after surgery
without adverse events92. This study showed that
selective COX-2 inhibition for pain control after
coronary artery bypass graft surgery was
associated with an increased incidence of
cardiovascular events.
58 Comparison of
Warfarin and Aspirin
for Symptomatic
Intracranial Arterial
Stenosis
3/31/05 Anticoagulation for treatment of intracranial arterial
stenosis was first used in 1955 and the use of
warfarin over aspirin had been supported by
retrospective studies93, 94. Neurologists were found
to be evenly divided between warfarin and aspirin
!"#$%&'$"()"*$+$,-&."
12
use. This study, the Warfarin-Aspirin Symptomatic
Intracranial Disease (WASID) Trial, showed that
warfarin had higher rates of adverse events and
no benefit compared to aspirin for intracranial
arterial stenosis.
59 Long-Term
Outcomes of
Coronary-Artery
Bypass Grafting
versus Stent
Implantation
5/26/05 Percutaneous coronary intervention (PCI) has
been increasingly used to treat multivessel
disease, but few trials compared the two for this
indication. This observational study found that
CABG is still superior to PCI with stenting for
treatment of multivessel disease in a large new
York state cohort.
60 Hydroxyurea
Compared with
Anagrelide in High-
Risk Essential
Thrombocythemia
7/7/05 Hydroxyurea is first-line therapy for high-risk
patients with essential thrombocytosis. Anagrelide
was found to decrease platelet counts and was
also used as first-line therapy for high-risk patients
despite a lack of evidence, and a higher cost. This
study showed hydroxyurea plus aspirin to be
superior to anagrelide.
61 Inhaled Nitric Oxide
for Premature Infants
with Severe
Respiratory Failure
7/7/05 Premature infants in respiratory distress who do
not respond to surfactant were thought to benefit
from inhaled nitric oxide due to pulmonary
vasodilation and decreased inflammation. A
single-center study showed a decrease in
bronchopulmonary disease and death in
moderately ill infants95. This larger, multicenter
randomized trial showed no benefit with the use of
inhaled nitric oxide for infants weighing less than
1500g.
62 An Evaluation of
Echinacea
angustifolia in
Experimental
Rhinovirus Infections
7/28/05 Echinacea has become a popular remedy for the
common cold since the Dietary Supplement Health
and Education Act in 1994 liberalized the
regulation of herbal medicines. This study showed
that echinacea held no benefit in symptom
duration or severity with rhinovirus infection
(common cold).
63 Developmental
Outcomes after Early
or Delayed Insertion
of Tympanostomy
Tubes
8/11/05 Official guidelines96 recommended myringotomy
with the insertion of tympanostomy tubes to relieve
persistent middle ear effusions in children out of
concern that conductive hearing loss would lead to
adverse effects on cognitive, speech, language,
and psychosocial development. This has become
one of the most common procedures of childhood.
This study showed no difference in development
between prompt and delayed tympanostomy
tubes.
64 Amnioinfusion for the
Prevention of the
Meconium Aspiration
Syndrome
9/1/05 A systematic review of randomized trials found
that amnioinfusion was associated with an overall
reduction in meconium aspiration syndrome97.
This study showed that amnioinfusion had no
benefit for preventing meconium aspiration
syndrome (or other major maternal/neonatal
disorders).
65 Early Invasive versus 9/15/05 Several studies comparing early to conservative
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13
Selectively Invasive
Management for
Acute Coronary
Syndromes
invasive therapy in acute coronary syndromes
showed the benefit of early invasive therapy, but
only the Fragmin and Fast Revascularization
during Instability in Coronary Artery Disease
(FRISC) II trial98 showed a reduction in mortality,
specifically in men. The American College of
Cardiology-American Heart Association guidelines
since recommended early invasive therapy for
high-risk patients with acute coronary syndromes
without ST-segment elevation99. This study, the
Invasive versus Conservative Treatment in
Unstable Coronary Syndromes (ICTUS) trial,
showed no mortality benefit of an early invasive
strategy given optimized medical therapy.
66 Long-Term
Vasodilator Therapy
in Patients with
Severe Aortic
Regurgitation
9/29/05 An earlier study showed nifedipine delayed the
need for surgery in patients with asymptomatic
chronic severe aortic regurtitation100 and
vasodilators have since been given a class I
recommendation by the American College of
Cardiology-American Heart Association101 and the
European Society of Cardiology102. This study
found no benefit with nifedipine or enalapril in
reducing or delaying the need for aortic valve
replacement and in treatment of aortic
regurgitation.
67 Continuous Positive
Airway Pressure for
Central Sleep Apnea
and Heart Failure
11/10/05 In small single-center trials, continuous positive
airway pressure (CPAP) significantly improved
disease progression and quality of life. In one
trial103, it also trended toward a reduction in
mortality and need for heart transplantation,
although this was before the common use of beta
blockade in heart failure treatment. Although this
study showed numerous benefits for the use of
CPAP in central sleep apnea in patients with heart
failure, it showed no mortality benefit nor benefit in
quality of life.
68 A Trial of
Contraceptive
Methods in Women
with Systemic Lupus
Erythematosus
12/15/05 Studies show that estrogens favor
development/exacerbation of lupus and that lupus
flares can occur in patients taking exogenous
estrogens. There are no official guidelines
addressing the issue, resulting in hesitance in
prescribing contraceptives. It is known that
maternal/fetal outcomes are worse if conception
occurs during active lupus flares and that there is
a high rate of elective abortions in women with
lupus104, suggesting the need for appropriate birth
control in this population. Both the first study and
the second study, the Oral Contraceptives-Safety
of Estrogens in Lupus Erythematosus National
Assessment (OC-SELENA) Trial, showed that the
use of oral contraceptives do not increase the
incidence of lupus flares.
69 Combined Oral
Contraceptives in
12/15/05 Both the first study and the second study, the Oral
Contraceptives-Safety of Estrogens in Lupus
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14
Women with
Systemic Lupus
Erythematosus
Erythematosus National Assessment (OCSELENA)
Trial, showed that the use of oral
contraceptives do not increase the incidence of
lupus flares.
70 The Risk Associated
with Aprotinin in
Cardiac Surgery
1/26/06 The majority of patients undergoing surgical
treatment for ST-elevation myocardial infarction
receive antifibrinolytic therapy to limit blood loss105.
In this observational study involving 4374 patients
undergoing revascularization, three agents
(aprotinin [1295 patients], aminocaproic acid [883],
and tranexamic acid [822]) as compared with no
agent (1374 patients) were prospectively
assessed with regard to serious outcomes by
propensity and multivariable methods. Aprotinin
was associated with increased risk of renal failure,
myocardial infarction or heart failure, and stroke.
71 Clozapine Alone
versus Clozapine and
Risperidone with
Refractory
Schizophrenia
2/2/06 Schizophrenia has poor response to any single
antipsychotic drug, resulting in the increasing
frequency of antipsychotic polypharmacy106. In this
randomized, double blind randomized clinical trial
patients with poor response to clozapine were
randomly assigned to augmentation with
risperidone or placebo. The addition of risperidone
to clozapine did not improve symptoms in patients
with severe schizophrenia
72 Saw Palmetto for
Benign Prostatic
Hyperplasia
2/9/06 Saw palmetto is used by over 2 million men in the
United States for the treatment of benign prostatic
hyperplasia107 and is commonly recommended as
an alternative to drugs approved by the Food and
Drug Administration. In this double-blind trial, 225
men over the age of 49 years who had moderateto-
severe symptoms of benign prostatic
hyperplasia were randomized to one year of
treatment with saw palmetto extract (160 mg twice
a day) or placebo. There was no significant
difference between the saw palmetto and placebo
groups in the change in AUASI scores (mean
difference, 0.04 point; 95 percent confidence
interval, –0.93 to 1.01), maximal urinary flow rate
(mean difference, 0.43 ml per minute; 95 percent
confidence interval, –0.52 to 1.38), prostate size,
residual volume after voiding, quality of life, or
serum prostate-specific antigen levels during the
one-year study.
73 Calcium plus Vitamin
D Supplementation
and the Risk of
Fractures
2/16/06 Observational evidence and data from randomized
clinical trials suggested that calcium or vitamin D
supplements or both may slow bone loss and
reduce the risk of falls. However, in this
randomized clinical trial involving 36,000
postmenopausal women, calcium with vitamin D
supplementation did not significantly reduce hip
fracture, and increased the risk of kidney stones
74 Glucosamine,
Chondroitin Sulfate,
2/23/06 The dietary supplements glucosamine and
chondroitin sulfate had been advocated as safe
!"#$%&'$"()"*$+$,-&."
15
and the Two in
Combination for
Painful Knee
Osteoarthritis
and effective options for the management of
symptoms of osteoarthritis. In this RCT 1583
patients with symptomatic knee osteoarthritis were
randomized to receive 1500 mg of glucosamine
daily, 1200 mg of chondroitin sulfate daily, both
glucosamine and chondroitin sulfate, 200 mg of
celecoxib daily, or placebo for 24 weeks.
Glucosamine and chondroitin sulfate alone or in
combination did not reduce pain effectively in the
overall group of patients with osteoarthritis of the
knee.
75 Efficacy and Safety of
Corticosteroids for
Persistent Acute
Respiratory Distress
Syndrome
4/20/06 Moderate dose corticosteroids was thought to
improve clinical outcomes in those with persistent
ARDS. In this trial 180 patients were randomly
assigned to methylprednisolone or placebo.
Mortality at 60 days between the two groups was
no different, suggesting that steroids should not
routinely be used in patients with ARDS
76 Pulmonary-Artery
versus Central
Venous Catheter to
Guide Treatment of
Acute Lung Injury
5/25/06 The pulmonary artery catheter (PAC) has been
advocated by many to be used in critically ill
patients in order to provide real time data on
hemodynamic markers, such as central venous
pressure and pulmonary artery wedge pressure.
This study randomized 1000 patients with
established acute lung injury to either a PAC or a
central venous catheter (CVC). PAC-guided
therapy did not improve survival or organ function
but was associated with more complications than
CVC-guided therapy.
77 A Controlled Trial of
Homocysteine
Lowering and
Cognitive
Performance
6/29/06 Observational studies suggested that plasma
homocysteine concentrations are inversely related
to cognitive function in older people108, and some
clinicians have prescribed folate, B12 and B6 to
preserve cognitive function. This double-blind,
placebo-controlled, randomized clinical trial
involving 276 healthy participants, 65 years of age
or older showed that despite intense
homocysteine-lowering treatment there was no
significant differences between the vitamin and
placebo groups in the scores on tests of cognition.
78 Effectiveness of
Atypical
Antipsychotic Drugs
in Patients with
Alzheimerʼs Disease
10/12/06 Second-generation (atypical) antipsychotic drugs
had been widely used to treat psychosis,
aggression, and agitation in patients with
Alzheimerʼs disease109. In this double-blind,
placebo-controlled trial, 421 outpatients with
Alzheimerʼs disease and psychosis, aggression, or
agitation were randomly assigned to receive
olanzapine (mean dose, 5.5 mg per day),
quetiapine (mean dose, 56.5 mg per day),
risperidone (mean dose, 1.0 mg per day), or
placebo. Overall, 24% of patients who received
olanzapine, 16% of patients who received
quetiapine, 18% of patients who received
risperidone, and 5% of patients who received
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16
placebo discontinued their assigned treatment
owing to intolerability (P = 0.009). No significant
differences were noted among the groups with
regard to improvement on the CGIC scale. This
suggests that adverse effects offset advantages in
the efficacy of atypical antipsychotic drugs for the
treatment of psychosis, aggression, or agitation in
patients with Alzheimerʼs disease
79 DHEA in Elderly
Women and DHEA or
Testosterone in
Elderly Men
10/19/06 DHEA and testosterone were widely promoted as
supplements. In this placebo-controlled,
randomized, double-blind study men were
randomized to placebo, testosterone, or DHEA.
Women received either DHEA or placebo. Neither
DHEA nor low-dose testosterone replacement in
elderly people was shown to have physiologically
relevant beneficial effects on body composition,
physical performance, insulin sensitivity, or quality
of life
80 Correction of Anemia
with Epoetin Alfa in
Chronic Kidney
Disease
11/16/06 In 2000, the KDOQI guidelines recommended that
the target level of hemoglobin should be 11.0 to
12.0 g per deciliter in patients with chronic kidney
disease110, whether or not they were receiving
dialysis, which was further updated to include an
expanded the target range to 11.0 to 13.0 g111. In
this study 1432 patients with chronic kidney
disease were studied, 715 of whom were
randomly assigned to target a Hg of 13.5g per
deciliter and 717 of whom were assigned to target
a Hg of 11.3g per deciliter. The use of a target
hemoglobin level of 13.5 g per deciliter (as
compared with 11.3 g per deciliter) was associated
with increased risk and no incremental
improvement in the quality of life.
81 Coronary Intervention
for Persistent
Occlusion after
Myocardial Infarction
12/7/06
In patients with acute coronary syndrome and
persistent total occlusion of the infarct-related
coronary artery after the time of myocardial
salvage, there was strong bias in favor of PCI in
addition to optimal medical therapy (OMT)112. In
this randomized clinical trial patients who had total
occlusion of the infarct related artery 3 to 28 days
after myocardial infarction were randomized to PCI
with stenting with OMT versus OMT alone. PCI did
not reduce the occurrence of death, reinfarction, or
heart failure, and there was a trend toward excess
reinfarction during 4 years of follow-up
82 Tympanostomy
Tubes and
Developmental
Outcomes at 9 to 11
Years of Age
1/18/07
Originally, it was thought that conductive hearing
loss due to persistent otitis media could lead to
long-term developmental impairment.113, 114 In
fact, official guidelines recommended that children
with middle-ear effusion persisting 3 or 4 months
have a myringotomy with insertion of
tympanostomy tubes.115, 116 This study showed
that prompt insertion of tympanostomy tubes in
infants with persistent middle-ear effusion did not
!"#$%&'$"()"*$+$,-&."
17
improve developmental outcomes, measured by
literacy, attention, and social skills in children at 9
to 11 years of age.
83 Long-Term
Outcomes with Drug-
Eluting Stents versus
Bare-Metal Stents in
Sweden
3/8/07
Many studies had shown that rates of in-stent
restenosis were lower with the use of drug-eluting
stents compared to bare-metal stents.117, 118 While
the FDA had approved these stents as safe for
patients with previously untreated lesions of a
certain size, the use of drug-eluting stents
expanded to include treatment in more
complicated patients with larger lesions.119-122
This prospective study showed that drug-eluting
stents were associated with higher mortality rates
compared to bare-metal stents.
84 Influence of
Computer-Aided
Detection on
Performance of
Screening
Mammography
4/5/07
At the time this article was published, many
mammography facilities in the U.S. had adopted
computer-aided detection to analyze digitized
mammograms and highlight suspicious areas for
review by a radiologist.123, 124 However, this study
found that the use of this technology was
associated with reduced accuracy of interpretation
for screening mammograms and that the
increased rates of biopsy associated with
computer-aided detection did not necessarily
translate to improved detection of invasive breast
cancer.
85 Optimal Medical
Therapy with or
without PCI for Stable
Coronary Disease
4/12/07
While treatment guidelines recommended an initial
approach of intensive medical therapy, reduction
of risk factors, and lifestyle modification (optimal
medical therapy) for patients with stable coronary
artery disease, percutaneous coronary
intervention (PCI) was still a common initial
treatment strategy for patients with stable coronary
artery disease at the time this study was done.125,
126 This study found that PCI added to optimal
medical therapy did not reduce the risk of death,
myocardial infarction or other major cardiovascular
events.
86 Effectiveness of
Adjunctive
Antidepressant
Treatment for Bipolar
Depression
4/26/07
Even though the FDA had not approved any of the
standard antidepressants for treatment of bipolar
depression at the time of this study, many
antidepressants were used as adjuncts to moodstabilizers
in patients with bipolar depression
without significant evidence of the efficacy or
potential risks of this treatment modality.127-130
This RCT showed that the use of a standard
antidepressant as an adjunctive treatment was not
associated with increased efficacy or with
increased risk of treatment-related affective
switch.
87 Randomized
Comparison of
Strategies for
Reducing Treatment
5/17/07
Treatment guidelines for patients with persistent
asthma whose symptoms are well controlled on an
inhaled corticosteroid can be stepped down to an
alternative, less intensive treatment131-133, such as
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18
in Mild Persistent
Asthma
a combination long-acting beta agonist and ICS, or
an antileukotriene like montelukast134. This
randomized controlled trial showed that patients
with asthma that was well controlled with the use
of inhaled fluticasone twice daily could be
switched to once-daily fluticasone plus salmeterol
without increased rates of treatment failure.
However, switching to montelukast resulted in
increased rates of treatment failure and decreased
asthma control.
88 Effect of
Rosiglitazone on the
Risk of Myocardial
Infarction and Death
from Cardiovascular
Causes
6/14/07
Rosiglitazone was introduced in 1999 and was
approved in type II diabetes mellitus because of its
ability to reduce blood glucose and Hgb A1C.135
This study looking at the relationship between use
of this drug and risk of cardiovascular disease was
done because cardiovascular disease is a
common cause of disease in diabetic patients.136
This meta-analysis found that rosiglitazone was
associated with a significant increase in the risk of
myocardial infarction and a near-significant
increase in the risk of cardiovascular-related death
and suggest reason for cautious use of this drug in
type II diabetics.
89 In Vitro Fertilization
with Preimplantation
Genetic Screening
7/5/07
Because a possible cause of low pregnancy rates
in women of advanced maternal age undergoing in
vitro fertilization (IVF) may be due to increased
prevalence of chromosomal abnormalities, the use
of preimplanation genetic screening had become
increasingly more common at the time of this
study, particularly in women of advanced maternal
age.137-139 However, this multicenter, double-blind
randomized controlled trial comparing IVF with
and without preimplantation genetic screening
found that screening significantly reduced rates of
ongoing pregnancies and live births after IVF in
women of advanced maternal age.
90 A Multicenter,
Randomized
Controlled Trial of
Dexamethasone for
Bronchiolitis
7/26/07
While corticosteroids were commonly used at the
time of this study to treat bronchiolitis in children,
evidence on the effectiveness of this treatment
modality was limited and results of prior studies
had been mixed.140-145 This randomized controlled
trial showed that a single dose of oral
dexamethasone administered in the emergency
room did not significantly reduce the rate of
hospital admission, the respiratory status after four
hours, or later outcomes in children with
moderate-to-severe bronchiolitis.
91 Saline or Albumin for
Fluid Resuscitation in
Patients with
Traumatic Brain
Injury
8/30/07 At the time of this study, no consensus had been
reached for the best choice of fluids for fluid
resuscitation in patients with traumatic brain injury.
As a result, both fluid resuscitation with albumin or
saline was advocated.146, 147 A prior study
comparing these two methods of fluid resuscitation
in patients in the intensive care unit showed no
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19
significant difference between the two, but there
was an increased number of deaths among
patients with traumatic brain injury who received
albumin.148 This study was a follow-up study in
this subgroup of patients and showed that fluid
resuscitation with albumin in patients with
traumatic brain injury was associated with higher
mortality rates than resuscitation with saline.
92 High-Dose Melphalan
versus Melphalan
plus Dexamethasone
for AL Amyloidosis
9/13/07
At the time of this study, high-dose melphalan with
autologous hematopoietic stem-cell rescue was
commonly used to treat patients with AL
amyloidosis but transplant-related mortality was
high.149-151 This randomized trial showed that AL
amyloidosis treatment with high-dose melphalan
plus autologous hematopoietic stem-cell transplant
was not superior to the outcome with standarddose
melphalan plus dexamethasone.
93 Outcomes at 2 Years
of Age after Repeat
Doses of Antenatal
Corticosteroids
9/20/07
While a single does of antenatal corticosteroids
given to women at risk for preterm delivery
reduces the risk of neonatal morbidity and
mortality as well as long-term neurologic sequelae,
infants born more than 7 days after the dose of
antennal corticosteroids had been shown to have
lower birth weight and increased perinatal
mortality compared to unexposed infants.152, 153
As a result, common practice was to repeat the
dose of antenatal corticosteroids after 7 or more
days even though there was no strong evidence to
support the benefit of this practice.154 The 2-year
results of this randomized controlled trial
comparing a single dose of antenatal steroids to
repeated doses of antenatal steroids in women at
risk for preterm delivery showed that even though
repeated doses of antenatal steroid reduced
neonatal morbidity, they did not change survival
free of major neurosensory disability or body size
at 2 years of age.
94 Long-Term
Outcomes after
Repeat Doses of
Antenatal
Corticosteroids
9/20/07
While evidence clearly supported the benefits of a
single dose of corticosteroids on reducing
perinatal morbidity and mortality, the optimal
benefit of antenatal corticosteroid therapy lasted
for 7 days.155 Even though the risks and benefits
of repeated doses of antenatal corticosteroids
beyond 7 days in women who continued to be at
risk for preterm delivery were unknown, this
became common practice in the United States, the
United Kingdom, and Australia.154, 156 The results
of this randomized controlled trial showed that
women who had been exposed to repeated doses
of corticosteroids did not differ significantly in
physical or neurocognitive measures as compared
to children exposed to a single dose of antenatal
corticosteroids. Additionally, there was a trend
toward higher rates of cerebral palsy in children
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20
who had been exposed to repeat doses of
corticosteroids.
95 Early Treatment with
Prednisolone or
Acyclovir in Bellʼs
Palsy
10/18/07
Both prednisolone and acyclovir were commonly
used, both alone and in combination for treatment
of Bellʼs palsy; however, the evidence for the
effectiveness of either of these treatments was
lacking.157, 158 This randomized, controlled trial
showed that while early treatment with
prednisolone significantly improved the chances of
complete recovery at 3 and 9 months, there was
no evidence of a benefit of acyclovir as
monotherapy or as an adjunct to prednisolone.
96 Lung Transplantation
and Survival in
Children with Cystic
Fibrosis
11/22/07
While lung transplantation was the most
aggressive therapy for end-stage lung disease and
cystic fibrosis was the most common indication for
children, the benefits on patientsʼ quality of life
was uncertain.159 Also, transplantation accounted
for a high percentage of deaths among cystic
fibrosis patients.160 This large retrospective study
showed that lung transplantation clearly improved
survival in less than one percent of patients with
cystic fibrosis and that prolongation of life by
means of lung transplantation should not be
expected in children with cystic fibrosis.
97 Rosuvastatin in Older
Patients with Systolic
Heart Failure
11/29/07 While there was some concern about the safety of
statins in heart failure patients particularly related
to skeletal and cardiac myopathy, multiple trials
suggested that the use of statins was associated
with better outcomes in heart failure patients,
including better effects on left ventricular function
and clinical status.161-167 This randomized
controlled trial showed that rosuvastatin did not
reduce the rate of death from cardiovascular
causes or death from any cause in patients with
systolic heart failure although it did reduce the
number of cardiovascular hospitalizations. The
drug did not increase rates of muscle-related or
other adverse events.
98 Dexamethasone in
Vietnamese
Adolescents and
Adults with Bacterial
Meningitis
12/13/07 While corticosteroids were commonly used in the
treatment of bacterial meningitis, evidence was
mixed as to whether or not this treatment could
reduce mortality rates and the risk of severe
neurologic sequelae in adults, particularly in
different settings outside of Europe.168-171 This
randomized control trial showed that
dexamethasone did not significantly improve
outcomes in Vietnamese adolescents and adults
with bacterial meningitis. There may be some
beneficial effect for patients with biologically
proven disease, including those who had
previously received antibiotic treatment.
99 Corticosteroids for
Bacterial Meningitis
in Adults in Sub-
12/13/07 Because the host inflammatory response
contributes significantly to neuronal injury in
bacterial meningitis, corticosteroids had been
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21
Saharan Africa incorporated into treatment guidelines as adjuvant
therapy.172-175 However, data on the use of
corticosteroids for bacterial meningitis in
developing countries or areas of high HIV
prevalence was limited. This randomized control
trial in Malawi showed that dexamethasone for
bacterial meningitis in an area with a high
prevalence of HIV did not reduce mortality or
morbidity.
100 Hydrocortisone
Therapy for Patients
with Septic Shock
1/10/08 Corticosteroids were widely used in patients with
septic shock although their use was
controversial176. Of note, low doses of long
duration showed a survival benefit177, 178, and
steroids were endorsed by clinical guidelines179.
The Corticosteroid Therapy of Septic Shock
(CORTICUS) study failed to show a mortality
benefit in those patients with septic shock.
101 Intensive Insulin
Therapy and
Pentastarch
Resuscitation in
Severe Sepsis
1/10/08 Aggressive blood glucose control was a widely
accepted practice based on data attained from
cardiac surgical patients180. This practice
continued despite evidence that it may cause
harm181. In the Efficacy of Volume Substitution and
Insulin Therapy in Severe Sepsis (VISEP) study
not only was no mortality benefit noted, the trial
was stopped early because of severe
hypoglycemic events leading to prolonged ICU
stays.
102 Aprotinin during
Coronary-Artery
Bypass Grafting and
Risk of Death
2/21/08 The use of Trasylol (Bayer HealthCare) in cardiac
surgery to reduce blood loss and maintain platelet
function was shown to lead to increase risk of inhospital
death and higher 5-year mortality182, 183.
Despite this, the manufacturer maintained a
favorable risk-benefit profile for the drug given the
available data while suspending worldwide
marketing. A retrospective analysis was performed
from the Premier Perspective Comparative
Database showed no benefit above that of
aminocaproic acid but did show increases in
inpatient mortality with respect to aprotinin vs.
aminocaproic acid.
103 The effect of
Aprotinin on Outcome
after Coronary-Artery
Bypass Grafting
2/21/08 In a single center, retrospective, observational
cohort study performed at Duke it was shown
looking at 10,275 consecutive patients who had
CABG there is an increase in both short term and
long term mortality with the use of Aprotinin.
104 Vasopressin versus
Norepinephrine
Infusion in Patient
with Septic Shock
2/28/08 Vasopression was thought to be a reasonable
adjunct in patients with septic shock based on
shock physiology184, 185. It was also thought that it
would reduce the use of catecholamines186. As
such it was used widely. This randomized trial
found no mortality benefit from the administration
of vasopressin as compared with norepinephrine
among patients treated with catecholamines for
shock.
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22
105 Anestheisia
Awareness and the
Bispectral Index
3/13/08 Bispectral index monitors (BIS) is an important
brain-function monitor for Anesthesiologists to
prevent sensory perception during surgery187, 188.
The FDA has approved this monitor. The B-Aware
study showed an absolute risk reduction of
anesthesia awareness189. The B-Unaware trial did
not result in lower rate of anesthesia awareness
nor lower use of volatile anesthetic gas.
106 Simvastatin with or
without Ezetimibe in
Familial
Hypercholesterolemia
4/3/08 It is well known that lowering LDL significantly
reduces cardiovascular events190, 191. This primary
prevention strategy was only limited by the side
effects seen with increasing doses of statins192. It
was thought that adding a second agent,
ezetimibe to statin therapy would further lower
LDL, thereby further reducing cardiovascular
events193, 194. In the ENHANCE trial, despite
significant incremental lowering of LDL the primary
end point of mean intima-media thickness of the
carotid-artery wall was not reduced.
107 Metformin versus
Insulin for the
Treatment of
Gestational Diabetes
5/8/08 Treatment gestational diabetes had consisted of
lifestyle modification and insulin treatment as this
was shown to improve prenatal outcomes195. Oral
metformin was thought to be favorable for
treatment in gestational diabetes because it does
not cause weight gain and not associated with
hypoglycemia196. Its use became controversial
because of the question of adverse perinatal
effects197. When metformin was compared with
insulin in an open labeled RCT, there was no
significant increase in perinatal complications.
108 A Comparison of
Aprotinin and Lysine
Analogues in High-
Risk Cardiac Surgery
5/29/08 There were three antifibrinolytic agents used in
cardiac surgery to minimize bleeding and reduce
transfusion requirements198, 199. All of the drugs
had been shown to reduce the need for blood
transfusion compared with placebo198, 200. There
was controversy surrounding which drug should
be used and led to variation in clinical practice201.
In the Blood Conservation Using Antifibrinolytics in
a Randomized Trial (BART) it was shown that
aprotinin led to increased risk of death as
compared to those receiving tranexamic acid or
aminocaproic acid.
109 Intensive Blood
Glucose Control and
Vascular Outcomes
in Patient with Type 2
Diabetes
6/12/08 A target A1C of 7.0% or less was the guideline for
most patients with diabetes202. However data were
inconsistent how glucose control played a role in
vascular disease203, 204. In the Action in Diabetes
and Vascular Disease (ADVANCE) trial, the
effects of glucose control on major vascular
outcomes were evaluated. There was no evidence
of reduction in macrovascular events and intensive
glucose control was associated with increased risk
of severe hypoglycemia and increased rate of
hospitalization.
110 Effects of Intensive 6/12/08 A target A1C of 7.0% or less was the guideline for
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23
Glucose Lowering in
Type 2 Diabetes
most patients with diabetes202. The Action to
Control Cardiovascular Risk in Diabetes
(ACCORD) trial found that a HbA1c target of less
that 7.0% sustained for 3.5 years increased
mortality and did not significantly reduce major
cardiovascular events compared to a more
permissive goal.
111 Rhythm Control
versus Rate Control
for Atrial Fibrillation
and Heart Failure
6/19/08 Available evidence suggested that patients with
atrial fibrillation have worse prognosis and an
independent risk factor for death than those with
sinus rhythm205, 206. Because of this, conversion to
sinus rhythm and maintenance with antiarrhythmic
drugs was regularly attempted207. The value in
preventing atrial fibrillation in those with heart
failure was not known208. The Atrial Fibrillation and
Congestive Heart Failure trial showed rhythmcontrol
did not reduce the rate of death from
cardiovascular causes as compared with ratecontrol.
112 Noninvasive
Ventilation in Acute
Cardiogenic
Pulmonary Edema
7/10/08 With the hope to avoid the complications of
tracheal intubation, non-invasive ventilator
strategies are often used to improve oxygenation,
reduce work of breathing and increase cardiac
output209-212. However, in this multicenter study, no
difference in the effect on short-term mortality
between standard O2 therapy and noninvasive
ventilation was found.
113 A Randomized Trial
of Arthroscopic
Surgery for
Osteoarthritis of the
Knee
9/11/08 Arthroscopic surgery is widely used for
osteoarthritis of the knee even in the face of scant
evidence of its efficacy213, 214. This failed to show a
benefit of arthroscopic surgery for treatment of
osteoarthritis of the knee as assessed by WOMAC
scores.
114 Prolonged Therapy of
Advanced Chroncic
Hepatitis C with Low-
Dose Peginterferon
12/4/08 Peginterferon and ribavirin is the mainstay of
therapy for Hepatitis C215. Treatment options for
patients who failed this primary therapy were
limited, but many physicians continue Hepatitis C
treatment for these refractory patients216. It was
thought that any viral suppression would lead to
clinically important endpoints217. The Hepatitis C
Antiviral Long-Term Treatment against Cirrhosis
(HALT-C) trial did not show a reduction in clinical
outcomes or progression of fibrosis.
115 Oral Prednisolone for
Preschool Children
with Acute Virus-
Induced Wheezing
1/22/09 Several sets of national guidelines recommend
that oral corticosteroids be given to preschool
aged children who present to a hospital with virusinduced
wheezing218. However, the data for
steroid use in this population is unclear. This large
randomized, double-blind, placebo-controlled trial
found no benefit of steroids among preschool
children presenting to the hospital with acute, mildto-
moderate virus-induced wheezing.
116 Quality of Life after
Late Invasive
2/19/09 Late opening (3-28) days after myocardial
infarction) of a completely occluded coronary
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24
Therapy
for Occluded Arteries
artery is a common practice, particularly in the
United States219-221. Such late opening is thought
to improve mortality, ventricular function, and
quality of life. Previously, the Occluded Artery
Trial (OAT), a large randomized study, found no
benefit in major cardiovascular events for this
therapy (see reversal #86, 2006). This study
reexamined OAT with respect to economic and
quality of life outcomes. Late opening of occluded
infarct-related arteries provided a marginal
advantage for physical function at 4 months that
was not sustained for the 3 year trial duration. Late
opening resulted in higher total medical costs and
lower quality-adjusted life expectancy at 2 years.
117 Intensive versus
Conventional
Glucose Control in
Critically Ill Patients
3/26/09 Tight glycemic control (81 to 108 mg per deciliter)
has been widely recommended and practiced in
intensive care units222, 223. The Normoglycemia in
Intensive Care Evaluation–Survival Using Glucose
Algorithm Regulation (NICE-SUGAR) trial showed
that tight control, as compared with conventional
glucose control, increased the absolute risk of
death at 90 days by 2.6 percentage points.
118 Mortality Results from
a Randomized
Prostate-Cancer
Screening Trial
3/26/09 The mortality benefit of routine prostate cancer
specific antigen (PSA) screening continues to be
debated. This large, randomized trial failed to
detect any mortality benefit of routine screening
among American men.
119 Rosuvastatin and
Cardiovascular
Events in Patients
Undergoing
Hemodialysis
4/2/09 Because of their significant cardiovascular risk,
hemodialysis users are recommended to take
statins according to clinical guidelines
worldwide224. A Study to Evaluate the Use of
Rosuvastatin in Subjects on Regular
Hemodialysis: An Assessment of Survival and
Cardiovascular Events (AURORA) found no
benefit in the combined end point of myocardial
infarction, stroke, or death from cardiovascular
causes among these patients, despite significant
improvements in LDL cholesterol.
120 Efficacy of
Esomeprazole for
Treatment of Poorly
Controlled Asthma
4/9/09 Acid reflux is thought to exacerbate wheezing
among asthmatic patients. Current guidelines
recommend that patients with poorly controlled
asthma, particularly those with nighttime
symptoms, be tested for gastroesophageal reflux
disease, even in the absence of heartburn
symptoms. If detected, proton-pump inhibitors
(PPI) are recommended in these patients225. This
study found that, despite a substantial incidence of
GERD in this population, the addition of a PPI did
not confer benefit.
121 Cognitive Function at
3 Years of Age after
Fetal Exposure to
Antiepileptic Drugs
4/16/09 Several sets of consensus guidelines (the
American Academy of Neurology the American
College of Obstetricians and Gynecologists and
the International League against Epilepsy226 do
not distinguish among antiepileptic drugs used
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25
during pregnancy with respect to teratogenetic
risks. The Neurodevelopmental Effects of
Antiepileptic Drugs (NEAD) study found that
valproic acid, as compared with other commonly
used drugs, was associated with poorer cognitive
function at 3 years of age.
122 Early versus
Delayed, Provisional
Eptifibatide in Acute
Coronary Syndromes
5/21/09 2007 guidelines from the American College of
Cardiology and the American Heart Association227
recommend that among patients with NSTEMI and
high-risk features aspirin and either clopidogrel or
a glycoprotein IIb/IIIa inhibitor be given before
angiography (i.e., early therapy) (class I
recommendation). This study, the EARLY ACS
trial, showed that contrary to this recommendaton,
the early use of eptifibatide was not superior to
eptifibatide post angiography, and likely resulted in
higher rates of bleeding.
123 Endoscopic versus
Open Vein-Graft
Harvesting in
Coronary-Artery
Bypass Surgery
7/16/09 Endoscopic harvesting of the saphenous vein for
coronary artery bypass surgery has swelled in
popularity. It is a procedure which eliminates the
need for the long incisions associated with open
harvesting, reduces wound infections, decreases
postoperative pain, and shortens length of stay in
the hospital. In fact, in 2005 the International
Society for Minimally Invasive Cardiothoracic
Surgery recommended that it should replace open
harvesting as standard of care228. This study
showed that endoscopic harvesting resulted in
higher rates of vein-graft failure at 12 to 18
months, and, at 3 years, higher rates of death,
myocardial infarction, or repeat revascularization.
124 A Randomized Trial
of Vertebroplasty for
Painful Osteoporotic
Vertebral Fractures
8/6/09 Vertebroplasty is a medical procedure where
cement is injected into fractured spinal bone, in
theory, restoring the original shape, diminishing
pain, and stabilizing the fragments. Interventional
neuroradiologists pioneered its use in the United
States in the 1990s. By the late 1990s, case
series were published, and technical details were
shared. Proponents of vertebroplasty lobbied
Medicare to fund the procedure, and in 2001, their
request was granted. In that year, more than
14,000 vertebroplasties were performed in the
United States, and by 2004, that number was
27,000229. Vertebroplasty quickly became a multimillion
dollar a year industry. In these paired
articles, the procedure was shown to be no better
than a sham procedure.
125 A Randomized Trial
of Vertebroplasty for
Osteoporotic Spinal
Fractures
8/6/09 same as above
126 Weight Lifting in
Women with Breast-
Cancer–Related
8/13/09 Breast-cancer survivors with lymphedema may
limit the use of the affected arm based upon
guidance from the American Cancer Society230.
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26
Lymphedema This randomized trial showed, that contrary to this
position, weight lifting improves the symptoms of
lymphedema.
127 Intensity of
Continuous Renal-
Replacement
Therapy in Critically
Ill Patients
10/22/09 Renal failure is associated with substantial
morbidity and mortality and is common among
patients requiring intensive care. In recent years,
there has been a widespread increase in the use
of higher-intensity continuous renal-replacement
therapy compared to lower intensity replacement
therapy among critically ill patients231, 232. This
large, multicenter, randomized, controlled trial of
intensity of renal support in acute kidney injury
(RENAL) indicates that such practice is not
justified, as high intensity therapy did not improve
mortality at 90 days
128 Revascularization
versus Medical
Therapy for Renal-
Artery Stenosis
11/12/09 Renal artery stenosis is associated with
hypertension and kidney disease, but it is unclear
if the relationship is causal. Despite this
uncertainty, data from studies in the United States
indicate that revascularization is performed in 16%
of patients with newly diagnosed atherosclerotic
renovascular disease and hypertension233. This
large randomized trial (ASTRAL) of
revascularization with medical management
versus medical management alone found
substantial risks but no evidence of benefit from
revascularization in this population.
129 A Trial of
Darbepoetin Alfa in
Type 2 Diabetes and
Chronic Kidney
Disease
11/19/09 The use of erythropoesis stimulating agents
among patients with anemia and chronic kidney
disease is widespread. The belief that this therapy
confers benefit is so strong that major clinical trials
have considered the use of placebo unnecessary
or even unethical234, 235. The Trial to Reduce
Cardiovascular Events with Aranesp Therapy
(TREAT) showed that the use of these agents did
not reduce the risk of either death or a
cardiovascular event or a renal event and was
associated with an increased risk of stroke.
130 Extended-Release
Niacin or Ezetimibe
and Carotid Intima–
Media Thickness
11/26/09 Zetia or Ezetimibe was licensed by the Food and
Drug Administration in 2002 based upon its ability
to reduce the LDL cholesterol level without major
short term side effects. Since that time, Zetia has
been prescribed widely to improve cardiovascular
risk. A number of other studies have suggested
that the net effect of Zetia may not be beneficial.
This current study shows that for one surrogate of
atherosclerotic disease the Zetia does not result in
the regression of carotid artery intimal medial
thickness, while niacin (another cardiovascular
drug) does. This study further undermines the
purported benefit of Zetia with respect to
cardiovascular risk.
131 Preoperative Biliary
Drainage for Cancer
1/14/10
Jaundice in surgical patients is postulated to
increase the rate of postoperative complications.
!"#$%&'$"()"*$+$,-&."
27
of the Head of the
Pancreas
Many surgical centers have employed biliary
drainage prior to surgical intervention for cancer of
the head of the pancreas, but there is conflicting
evidence regarding its effect on morbidity and
mortality.236-241 This multicenter, randomized trial
found that routine preoperative biliary drainage
increases the rate of serious complications without
a mortality benefit.
132 Outcomes after
Internal versus
External
Tocodynamometry
for Monitoring Labor
1/28/10
The Dutch Society of Obstetrics and Gynecology
recommends the routine use internal
tocodynamometry during all cases of induction or
augmentation of labor. Likewise, the American
College of Obstetrics and Gynecology advocates
its use in numerous circumstances. However,
these recommendations are grounded in expert
opinion, and smaller trials have failed to
demonstrate a net benefit with internal versus
external tocodynamometry.242, 243 In a multicenter,
randomized trial, the authors found that internal
tocodynamometry did not reduce the rate of
operative deliveries, adverse neonatal outcomes,
rates of use of analgesia or antibiotics, or time to
delivery .
133 Comparison of
Dopamine and
Norepinephrine in the
Treatment of Shock
3/4/10
Consensus guidelines recommend both dopamine
and norepinephrine as first line agents in the
treatment of patients with shock, and many
physicians favor dopamine in cardiogenic
shock.244-246 The Sepsis Occurrence in Acutely Ill
Patients (SOAP) study observationally showed
that dopamine administration increased the risk of
death in the intensive care unit.247 This
randomized study found that dopamine
administration resulted in about twice as many
arrhythmic events in the total cohort, while
subgroup analysis demonstrated higher 28-day
mortality rates in patients with cardiogenic shock.
134 Lenient versus Strict
Rate Control in
Patients with Atrial
Fibrillation
4/15/10
The American Heart Association/American
College of Cardiology/European Society of
Cardiology guidelines recommend strict rate
control (resting heart rate < 80 beats per minute
and exercise heart rate < 110 beats per minute) to
reduce morbidity and mortality from atrial
fibrillation, based upon expert consensus.248 This
study found that lenient rate control (resting heart
rate <110 beats="" minute="" noninferior="" p="" per="" to="" was="">
strict rate control and much easier to achieve in
patients with permanent atrial fibrillation.
135 Effects of
Combination Lipid
Therapy in Type 2
Diabetes Mellitus
4/29/10
Fibrate therapy has long been used in the
treatment of dyslipidemia in type II diabetes.
Though statins are considered primary therapy to
reduce the risk of cardiovascular events, rates
remain elevated despite use. Two large previous
studies of fibrate therapy in type II diabetics
conflicted with regard to their effect on
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28
cardiovascular events.249, 250 The Action to Control
Cardiovascular Risk in Diabetes (ACCORD) Lipid
study demonstrated here that statin and fibrate
combination therapy did not differ in outcomes
compared with statin therapy alone at similar
levels of serum lipids.
136 Effects of Intensive
Blood-Pressure
Control in Type 2
Diabetes Mellitus
4/29/10
The Seventh Report of the Joint National
Committee on Prevention, Detection, Evaluation,
and Treatment of High Blood Pressure
recommended initiating blood pressure treatment
in patients with diabetes who have systolic blood
pressures of 130 mmHg or greater.251 This
recommendation was based upon expert opinion,
given the higher risk of diabetic patients for
adverse cardiovascular events even at
prehypertensive levels. The Action to Control
Cardiovascular Risk in Diabetes (ACCORD) study
tested whether targeting a systolic blood pressure
below 120 mmHg in comparison to a target below
140 mmHg would reduce major cardiovascular
events. The intensive-therapy group did not differ
from the standard-therapy group with respect to
the primary composite outcome of nonfatal
myocardial infarction, nonfatal stroke, or
cardiovascular death. Intensive treatment did
lower the stroke risk in intensively treated patients,
but the absolute risk reduction was 0.21% and
also resulted in more adverse events related to
therapy.
137 Aspirin plus Heparin
or Aspirin Alone in
Women with
Recurrent
Miscarriage
4/29/10
The pathogenesis of women with unexplained,
recurrent miscarriage may be similar to those with
antiphospholipid antibody syndrome, who are
generally treated with antiplatelet and
anticoagulation therapy during pregnancy. Limited
studies in women with unexplained, recurrent
miscarriage have shown a benefit of aspirin plus
low-molecular-weight heparin.252-254 However, this
large, multicenter study which randomized women
with unexplained, recurrent miscarriage to aspirin
plus heparin, aspirin alone, or placebo failed to
demonstrate a benefit in live-birth rate with aspirin
plus heparin or aspirin alone.
138 Quality Indicators for
Colonoscopy and the
Risk of Interval
Cancer
5/13/10
Professional societies have advocated cecal
intubation as a quality-indicator for colonoscopy
without previous validation of the measure.255, 256
However, this large, retrospective study failed to
demonstrate cecal intubation as a predictor of
interval colon cancer.
139 Long-Term Outcome
of Open or
Endovascular Repair
of Abdominal Aortic
Aneurysm
5/20/10
Endovascular repair improves perioperative
survival over conventional open repair of
abdominal aortic aneurysms. However, the benefit
does not last beyond the second post-op year in
two year follow-up studies, and long term data on
morbidity and mortality are lacking.257-260 After a
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29
median follow-up of 6.4 years, this randomized,
controlled trial showed similar survival rates but
higher reintervention rates for endovascular repair,
due to reduced endograft durability.
140 A Randomized Trial
of Treatment for
Acute Anterior
Cruciate Ligament
Tears
7/22/10
Reconstruction for acute anterior cruciate ligament
(ACL) tears is a common and expensive treatment
option, while structured rehabilitation is less
frequently offered. However, there is insufficient
evidence from randomized trials to inform current
practice.261, 262 This trial randomized young, active
adults to structured rehabilitation plus early ACL
reconstructive surgery or structured rehabilitation
with delayed ACL reconstruction. The authors
found no advantage of routine early surgical
reconstruction as measured by change in the
Knee Injury and Osteoarthritis Outcome Score
(KOOS4), indicating that more than half of all
surgical reconstructions can be reasonably
avoided. Although 23/59 patients in the latter
group eventually opted for surgery, the results
were similar when accounting for treatment
actually received.
141 CPR with Chest
Compression Alone
or with Rescue
Breathing
7/29/10
Nearly a half century after chest compression and
rescue breathing were proposed as routine
cardiopulmonary resuscitation (CPR)263 have the
most fundamental assumptions been questioned.
Two randomized trials in this issue both show no
benefit from rescue breathing when added to
chest only compression. The results of these
studies have fueled greater skepticism, and some
editorialists have called for trials to test whether
any CPR is better than a still lesser strategy of
automated external defibrillator alone264.
142 Compression-Only
CPR or Standard
CPR in Out-of-
Hospital Cardiac
Arrest
7/29/10
Same as above
143 Suicide-Related
Events in Patients
Treated with
Antiepileptic Drugs
8/5/10
The Food and Drug Administration issued a safety
warning in January 2008 on the risk of suicidality
associated with anti-epileptic drugs based upon
the results of a meta-analysis that showed a twofold
increased risk of suicidality (defined as
suicidal ideation or behavior). However, this
assessment was limited by a lack of standardized
definition of suicidality among the pooled trials.
The authors here examined the association of
anti-epileptic drugs and suicide-related events
(attempted or completed suicides) in a casecontrol
analysis, stratifying by clinical
comorbidities. Treatment with anti-epileptic drugs
did not increase the risk of suicide-related events
in patients with epilepsy but did increase the risk
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30
among patients with depression and among those
without epilepsy, depression, or bipolar disorder.
144 A Randomized,
Controlled Trial of
Early versus Late
Initiation of Dialysis
8/12/10
Clinical practice guidelines from 1997 have
recommended early initiation of dialysis based
upon nonrandomized data suggesting improved
survival and quality of life.265 However, since that
time, observational data have suggested a net
harm with early initiation.266-268 This study showed
that early initiaton of dialysis (estimated glomerular
filtration rate [GFR] between 10.0 to 14.0 ml per
minute per 1.73 m2 of body-surface area) did not
improve survival or clinical outcomes when
compared with the late-start group (estimated
GFR 5.0-7.0 ml per minute per 1.73 m2 of bodysurface
area).
145 Gentamicin–Collagen
Sponge for Infection
Prophylaxis in
Colorectal Surgery
9/9/10
The gentamicin-collagen sponge has been
approved for use in numerous countries and used
in millions of patients worldwide since 1985. A
single-center, randomized trial showed a 70%
decrease in surgical-site infection with
implantation of the sponge.269 This large,
multicenter, phase 3 trial however showed that
gentamicin-collagen sponge paradoxically resulted
in significantly more surgical-site infections, was
associated with more visits to the emergency room
or surgical office, and more frequently precipitated
rehospitalization for the infection.
146 Effects of CYP2C19
Genotype on
Outcomes of
Clopidogrel
Treatment
10/28/10
The CYP2C19 gene is involved in the conversion
of clopidogrel to its active metabolite, and patients
with certain genetic variants (“poor metabolizers”)
have been shown to be at higher risk for recurrent
cardiovascular events. The Food and Drug
Administration issued a black-box warning
regarding the reduced efficacy of clopidogrel in
patients who are carriers of two loss-of-function
allleles in the CYP2C19 gene. However, this
statement was based upon observational data
from only clopidogrel-treated patients and did not
include data from large, randomized controlled
trials to reduce the possibility of confounding.270-272
The authors of the present study pooled data from
two large, randomized controlled trials, and
showed that among patients with acute coronary
syndromes or atrial fibrillation, the safety and
efficacy of clopidogrel compared with placebo are
consistent, regardless of CYP2C19 loss-offunction
carrier status.
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31
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