Jalpari Dive Resorts_I am seriously planning on starting a scuba diving instruction facility somewhere on the East Coast of India if this is feasible.

 Jalpari Dive Resorts

We all think that scuba diving must be very difficult thing to do. I was fascinated by scuba diving since the time I saw James Bond’s “Thunder ball” movie. My dream came true recently. When I visited Cozumel along with my wife Shobha and son Akhilesh Iyer.

It was a very reasonable amount of $75 per person for a two hour instruction and diving package which is more or less the usual amount charged by most of the diving shops in and around Cozumel.

We talked with Pepe’s dive shop situated on the ground floor of the coral Princess dive resort and golf hotel on Cozumel this is somewhat nearer to the barracuda point on the Northwest point of the island.

After signing some disclaimer forms which were more of a formality,(“the instructor telling us to leave the areas where we have a problem just blank”) we put on our wet suits and then the theory part off the instruction started which more or less lasted about 15 minutes mainly explaining about the regulator and how the compressed air cylinder is connected to the regulator and how to fill the buoyancy jacket and use the weight belt and use the difference between the two in order to either sink deeper are to float on the surface.

The aluminum cylinder although not extremely heavy is about 30 to 40 pounds in weight I think and also there is a weight belt which once again is I think measured according to the size of the person.

We slowly entered the swimming pool and started practicing breathing underwater using the regulator and also how to clear our facemasks if some water enters inside the mask.

We also practiced taking out the regulator from the mouth and reinserting and also using a buddy regulator for emergency breathing.

All the time I was thinking that during this instruction I may not even be able to get out of the swimming pool because I was having this psychological feeling that I would still have to come up onto the surface before I can breathe all the while I was breathing underwater using the compressed air.

After about 15 minutes of doing this the instructor wanted us to walk down to the seashore and jump into the sea. My son had ability no problem doing this but I was quite hesitant and also when I jumped I jumped wrong and fell on my stomach and was quite disoriented.

The instructor was very good and helped me a lot because we were jumping from the shore there was a strong current and waves pushing us towards the shore and he had to literally drag me into the deeper water so that we could see and enjoy the sea creatures.

Once the early jitters went away it was an amazing sight watching the colorful fish swimming by and looking at some manta ray sliding along the bottom of the seafloor.

We must’ve spent about 25 to 30 minutes underwater but it felt like it was less than 10 minutes and I was really hooked.

I think we Indians are missing out on many of the wonders of the sea mainly because of our conservative attitudes and some stupid bureaucracies.

I am seriously planning on starting a scuba diving instruction facility somewhere on the East Coast of India if this is feasible.

British, Baniaya, Bano Biwi, Beef Beer Politics of Bharath

British, Baniaya, Bano Biwi, Beef Beer Politics of Bharath.

Yesterday 9/30/2015 I was listening to an India times Debate what I call BOW BOW debate. Where like  a bunch of fighting dogs various political spokes persons  try to  outshout their opponents  while the  Moderator the  fearless –Arnab  Goswami-- keeps  repeating  simple questions  which try to make  black and white out of a grey situation.

The debate was about the   crowd lynching of a Muslim in UP on the alleged crime of eating beef.

At the end of the  debate  the  Moderator  asks  a  simple thing   can  we all  say  ‘No more Beef  politics ?”

Except for one person, everyone else refused to say that statement.

They were trying to twist and turn to accommodate their party ideology to the circumstances with a view to the election box.

Today I also heard comment made by my son “what are you doing in Medicine? You should go and teach History in a college. This comment was made after I was trying to explain about Armenian Christians  and  the genocide of Armenians  by Turks .Which in turn was  an a occasion  to discuss  Armenia because  we were going to  Montreal  in Canada  to attend  my cousin  Raffi Narayan  son  of  Anoush Narayan(an Armenian Christian)  and  Natesa Laxmi Narayanan (A south Indian Brahmin   (Tamil Iyer)

The I thought   I should write a book about the politics of India

British, Baniaya, Bano Biwi, Beef Beer Politics of Bharath was an inspired title.

There can be many more things put in to the mix like Aryan/Dravidian/

Brahmin/dalith majority/minority

Mandal/anti reservation

Etc etc  

I hope I succeed.

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

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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

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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

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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

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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.

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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

!"#$%&'$"()"*$+$,-&."

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.

!"#$%&'$"()"*$+$,-&."

31

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