Title
 The erbium micropeel : a prospective , randomized trial of the effects of two fluence settings on facial photoaging .

 ABSTRACT BACKGROUND
 Recent studies have suggested that a series of low-energy , single-pass ablative laser resurfacing micropeels can reduce photoaging with decreased downtime . This randomized , prospective single-blinded trial sought to determine the ideal settings of sequential erbium : yttrium-aluminum-garnet ( Er : YAG ) laser treatments that maximize efficacy and patient satisfaction .

 ABSTRACT METHODS
 Forty-six subjects with mild-to-moderate facial dyschromia and rhytides were evenly randomized to two Er : YAG treatment arms . Patients in the lower fluence ( LF ) ( 2.5 J/cm2 ) and higher fluence ( HF ) ( 3.8 J/cm2 ) groups each received three one-pass , full-face treatments one month apart . Patient and investigator assessments of rhytides , dyschromia and global appearance were performed at baseline and at four , eight and 20 weeks using a nominal scale from 1 – 4 . Adverse events and patient satisfaction were also evaluated .

 ABSTRACT RESULTS
 Patient scores showed rhytid improvement only with HF treatments . Investigator scores at three months post-treatment showed dyschromia was significantly improved in both study arms , with a 24 and 36 percent reduction for the LF and HF groups , respectively . Global appearance scores improved by 25 and 32 percent , respectively . A trend towards greater post-procedure erythema and time-to-erythema resolution was observed in the HF group . Mild peeling was the most common adverse event . Individuals who underwent LF treatments were more likely to pursue future treatments .

 ABSTRACT CONCLUSIONS
 Both settings resulted in moderate but significant improvement in dyschromia , although only HF treatment improved rhytides . The decreased downtime of LF treatments made this the preferred choice of patients .

Title

The

erbium

micropeel

a

prospective

randomized

trial

of

the

effects

of

two

fluence

settings

on

facial

photoaging

ABSTRACT BACKGROUND

Recent

studies

have

suggested

that

a

series

of

low-energy

single-pass

ablative

laser

resurfacing

micropeels

can

reduce

photoaging

with

decreased

downtime

This

randomized

prospective

single-blinded

trial

sought

to

determine

the

ideal

settings

of

sequential

erbium

yttrium-aluminum-garnet

Er

YAG

laser

treatments

that

maximize

efficacy

and

patient

satisfaction

ABSTRACT METHODS

Forty-six

subjects

with

mild-to-moderate

facial

dyschromia

and

rhytides

were

evenly

randomized

to

two

Er

YAG

treatment

arms

Patients

in

the

lower

fluence

LF

and

higher

fluence

HF

groups

each

received

three

one-pass

full-face

treatments

one

month

apart

Patient

and

investigator

assessments

of

rhytides

dyschromia

and

global

appearance

were

performed

at

baseline

and

at

four

eight

and

weeks

using

a

nominal

scale

from

Adverse

events

and

patient

satisfaction

were

also

evaluated

ABSTRACT RESULTS

Patient

scores

showed

rhytid

improvement

only

with

HF

treatments

Investigator

scores

at

three

months

post-treatment

showed

dyschromia

was

significantly

improved

in

both

study

arms

with

a

and

percent

reduction

for

the

LF

and

HF

groups

respectively

Global

appearance

scores

improved

by

and

percent

respectively

A

trend

towards

greater

post-procedure

erythema

and

time-to-erythema

resolution

was

observed

in

the

HF

group

Mild

peeling

was

the

most

common

adverse

event

Individuals

who

underwent

LF

treatments

were

more

likely

to

pursue

future

treatments

ABSTRACT CONCLUSIONS

Both

settings

resulted

in

moderate

but

significant

improvement

in

dyschromia

although

only

HF

treatment

improved

rhytides

The

decreased

downtime

of

LF

treatments

made

this

the

preferred

choice

of

patients


Title
 Targeting mRNA splicing as a potential treatment for Duchenne muscular dystrophy .

 ABSTRACT GENERAL
 Several clinical trials have recently demonstrated that oligonucleotide-based drugs induced targeted exon skipping in dystrophin pre-mRNA in Duchenne muscular dystrophy patients , resulting in novel expression of a truncated but functional isoform of the dystrophin protein . Such exon skipping therapy has the potential to convert the lethal Duchenne phenotype into the less severe Becker phenotype . This splice switching technology has been shown to be very well tolerated and may become the first gene-specific therapy , if approved , for the treatment of Duchenne muscular dystrophy .

Title

Targeting

mRNA

splicing

as

a

potential

treatment

for

Duchenne

muscular

dystrophy

ABSTRACT GENERAL

Several

clinical

trials

have

recently

demonstrated

that

oligonucleotide-based

drugs

induced

targeted

exon

skipping

in

dystrophin

pre-mRNA

in

Duchenne

muscular

dystrophy

patients

resulting

in

novel

expression

of

a

truncated

but

functional

isoform

of

the

dystrophin

protein

Such

exon

skipping

therapy

has

the

potential

to

convert

the

lethal

Duchenne

phenotype

into

the

less

severe

Becker

phenotype

This

splice

switching

technology

has

been

shown

to

be

very

well

tolerated

and

may

become

the

first

gene-specific

therapy

if

approved

for

the

treatment

of

Duchenne

muscular

dystrophy


Title
 Discovery of TAK-733 , a potent and selective MEK allosteric site inhibitor for the treatment of cancer .

 ABSTRACT GENERAL
 A novel 5-phenylamino-8-methylpyrido [ 2,3-d ] pyrimidine-4,7 ( 3H ,8 H ) - dione series of MEK inhibitors has been developed using structure-based drug design . Lead optimization of this series led to the discovery of TAK-733 . This was advanced to Phase I clinical studies for cancer treatment .

Title

Discovery

of

a

potent

and

selective

MEK

allosteric

site

inhibitor

for

the

treatment

of

cancer

ABSTRACT GENERAL

A

novel

H

dione

series

of

MEK

inhibitors

has

been

developed

using

structure-based

drug

design

Lead

optimization

of

this

series

led

to

the

discovery

of

This

was

advanced

to

Phase

I

clinical

studies

for

cancer

treatment


Title
 Predictors of cessation in smokers suspected of TB : Secondary analysis of data from a cluster randomized controlled trial .

 ABSTRACT BACKGROUND
 Smoking cessation services are rarely found within health services in low income countries . Given the interactions between Tuberculosis ( TB ) and tobacco , including cessation support within TB programs offers a promising cost-effective solution . We conducted secondary analysis of data from a cluster randomized controlled trial of smoking cessation in health centers in Pakistan to identify predictors of continuous and short-term abstinence in smokers suspected of TB using cigarettes or hookah .

 ABSTRACT METHODS
 Predictor variables of those continuously abstinent at 5 and 25 weeks post quit-date ( continuous abstinence ) and those abstinent only at 5 weeks ( short-term abstinence ) were compared with those who continued smoking and with each other . Self-reported abstinence at both time points was confirmed biochemically .

 ABSTRACT RESULTS
 Data obtained from 1955 trial participants were analyzed . The factors that predicted continued smoking when compared to continuous abstinence were : being older RR 0.97 ( 0.95 to 0.98 ) , smoking higher quantities of tobacco RR 0.975 ( 0.97 to 0.98 ) and sharing a workplace with other smokers RR 0.88 ( 0.77 to 0.99 ) . Those with a confirmed TB diagnosis were more likely to remain continuously abstinent than those without RR 1.27 ( 1.10-1.47 ) .

 ABSTRACT CONCLUSIONS
 Those diagnosed with TB are more likely to be abstinent than those diagnosed with other respiratory conditions . Beyond this , predictors of continued smoking in Pakistan are similar to those in high income contexts . Taking advantage of the ' teachable moment ' that a TB diagnosis provides is an efficient means for resource-poor TB programs in low income settings to increase tobacco cessation and improve health outcomes .

Title

Predictors

of

cessation

in

smokers

suspected

of

TB

Secondary

analysis

of

data

from

a

cluster

randomized

controlled

trial

ABSTRACT BACKGROUND

Smoking

cessation

services

are

rarely

found

within

health

services

in

low

income

countries

Given

the

interactions

between

Tuberculosis

TB

and

tobacco

including

cessation

support

within

TB

programs

offers

a

promising

cost-effective

solution

We

conducted

secondary

analysis

of

data

from

a

cluster

randomized

controlled

trial

of

smoking

cessation

in

health

centers

in

Pakistan

to

identify

predictors

of

continuous

and

short-term

abstinence

in

smokers

suspected

of

TB

using

cigarettes

or

hookah

ABSTRACT METHODS

Predictor

variables

of

those

continuously

abstinent

at

and

weeks

post

quit-date

continuous

abstinence

and

those

abstinent

only

at

weeks

short-term

abstinence

were

compared

with

those

who

continued

smoking

and

with

each

other

Self-reported

abstinence

at

both

time

points

was

confirmed

biochemically

ABSTRACT RESULTS

Data

obtained

from

trial

participants

were

analyzed

The

factors

that

predicted

continued

smoking

when

compared

to

continuous

abstinence

were

being

older

RR

to

smoking

higher

quantities

of

tobacco

RR

to

and

sharing

a

workplace

with

other

smokers

RR

to

Those

with

a

confirmed

TB

diagnosis

were

more

likely

to

remain

continuously

abstinent

than

those

without

RR

ABSTRACT CONCLUSIONS

Those

diagnosed

with

TB

are

more

likely

to

be

abstinent

than

those

diagnosed

with

other

respiratory

conditions

Beyond

this

predictors

of

continued

smoking

in

Pakistan

are

similar

to

those

in

high

income

contexts

Taking

advantage

of

the

teachable

moment

that

a

TB

diagnosis

provides

is

an

efficient

means

for

resource-poor

TB

programs

in

low

income

settings

to

increase

tobacco

cessation

and

improve

health

outcomes


Title
 Acid suppression in duodenal ulcer : a meta-analysis to define optimal dosing with antisecretory drugs .

 ABSTRACT GENERAL
 FVMany different dosage schedules of antisecretory drugs for the treatment of duodenal ulcer are recommended . The relationship between degree of acid suppression and therapeutic efficacy has not been precisely defined for these drugs . We have examined the association between suppression of intragastric acidity and duodenal ulcer healing rates for a number of therapeutic regimens . For the H2 receptor antagonists alone , the most significant correlation with healing rates was with suppression of intragastric acidity at night ( r = 0.926 ; p = 0.0001 ) . When other classes of drug : high dose antacid , omeprazole and a synthetic prostaglandin ( enprostil ) were included in the analysis , the closest correlation was with suppression of total 24 hour intragastric acidity ( r = 0.911 ; p less than F0 .0001 ) . Stepwise linear regression analysis was used to investigate the relative contributions to healing of suppression of acidity during the day and night . Suppression of nocturnal acidity was found to be the single most important factor in explaining healing rates . No further benefit was obtained with daytime suppression for H2 receptor antagonists ; suppression of acidity at night accounted for 86.1 % of the observed variation in healing rates among different regimens of H2 receptor antagonists . When all classes of drugs were analysed , inclusion of daytime suppression produced a significant improvement in correlation over nocturnal suppression alone . Drug regimens providing potent suppression of nocturnal acidity produce the highest healing rates in controlled clinical trials . The healing rate for any dose regimen of an antisecretory drug can be predicted from a knowledge of its effect on intragastric acidity . For the H2 receptor antagonists , suppression of nocturnal acidity is the most relevant in this context . Moderate suppression of acidity achieves ulcer healing rates at four to eight weeks which are comparable with those seen with potent suppression at two to four weeks . Increasing degrees of suppression merely accelerate healing .

Title

Acid

suppression

in

duodenal

ulcer

a

meta-analysis

to

define

optimal

dosing

with

antisecretory

drugs

ABSTRACT GENERAL

FVMany

different

dosage

schedules

of

antisecretory

drugs

for

the

treatment

of

duodenal

ulcer

are

recommended

The

relationship

between

degree

of

acid

suppression

and

therapeutic

efficacy

has

not

been

precisely

defined

for

these

drugs

We

have

examined

the

association

between

suppression

of

intragastric

acidity

and

duodenal

ulcer

healing

rates

for

a

number

of

therapeutic

regimens

For

the

receptor

antagonists

alone

the

most

significant

correlation

with

healing

rates

was

with

suppression

of

intragastric

acidity

at

night

r

p

When

other

classes

of

drug

high

dose

antacid

omeprazole

and

a

synthetic

prostaglandin

enprostil

were

included

in

the

analysis

the

closest

correlation

was

with

suppression

of

total

hour

intragastric

acidity

r

p

less

than

Stepwise

linear

regression

analysis

was

used

to

investigate

the

relative

contributions

to

healing

of

suppression

of

acidity

during

the

day

and

night

Suppression

of

nocturnal

acidity

was

found

to

be

the

single

most

important

factor

in

explaining

healing

rates

No

further

benefit

was

obtained

with

daytime

suppression

for

receptor

antagonists

suppression

of

acidity

at

night

accounted

for

of

the

observed

variation

in

healing

rates

among

different

regimens

of

receptor

antagonists

When

all

classes

of

drugs

were

analysed

inclusion

of

daytime

suppression

produced

a

significant

improvement

in

correlation

over

nocturnal

suppression

alone

Drug

regimens

providing

potent

suppression

of

nocturnal

acidity

produce

the

highest

healing

rates

in

controlled

clinical

trials

The

healing

rate

for

any

dose

regimen

of

an

antisecretory

drug

can

be

predicted

from

a

knowledge

of

its

effect

on

intragastric

acidity

For

the

receptor

antagonists

suppression

of

nocturnal

acidity

is

the

most

relevant

in

this

context

Moderate

suppression

of

acidity

achieves

ulcer

healing

rates

at

four

to

eight

weeks

which

are

comparable

with

those

seen

with

potent

suppression

at

two

to

four

weeks

Increasing

degrees

of

suppression

merely

accelerate

healing


Title
 Potential impact of amyloid imaging on diagnosis and intended management in patients with progressive cognitive decline .

 ABSTRACT GENERAL
 Florbetapir F18 has been approved by the Food and Drug Administration for in vivo assessment of amyloid pathology in patients undergoing evaluation for Alzheimer disease ( AD ) . The aim of this study was to determine the impact of amyloid imaging on the diagnoses and management of patients undergoing evaluation for cognitive decline . Patients were recruited to participate at 19 clinical sites . The site physician provided a provisional diagnosis , an estimate of their diagnostic confidence , and their plan for diagnostic evaluation and management both before and after receiving the results from amyloid imaging with florbetapir F18 . Analyses compared the frequency of AD and non-AD diagnoses , plans for ancillary testing , and intended patient management before and after florbetapir imaging . A total of 229 patients participated in the trial ( 113 amyloid positive , 116 amyloid negative ) . After receiving the results of the florbetapir scan , diagnosis changed in 125/229 , or 54.6 % [ 95 % confidence intervals ( CI ) , 48.1 % -60.9 % ] , of cases , and diagnostic confidence increased by an average of 21.6 % ( 95 % CI , 18.3 % -24.8 % ) . A total of 199/229 or 86.9 % ( 95 % CI , 81.9 % -90.7 % ) of cases had at least 1 change in their management plan . Intended cholinesterase inhibitor or memantine treatment increased by 17.7 % ( 95 % CI , 11.8 % -25.8 % ) of all cases with positive scans and decreased by 23.3 % ( 95 % CI , 16.5 % -31.8 % ) of all those with negative scans . Among subjects who had not yet undergone a completed work up , planned brain structural imaging ( computed tomographic/magnetic resonance imaging ) decreased by 24.4 % ( 95 % CI , 17.5 % -32.8 % ) and planned neuropsychological testing decreased by 32.8 % ( 95 % CI , 25.0 % -41.6 % ) . In summary , amyloid imaging results altered physician 's diagnostic thinking , intended testing , and management of patients undergoing evaluation for cognitive decline .

Title

Potential

impact

of

amyloid

imaging

on

diagnosis

and

intended

management

in

patients

with

progressive

cognitive

decline

ABSTRACT GENERAL

Florbetapir

has

been

approved

by

the

Food

and

Drug

Administration

for

in

vivo

assessment

of

amyloid

pathology

in

patients

undergoing

evaluation

for

Alzheimer

disease

AD

The

aim

of

this

study

was

to

determine

the

impact

of

amyloid

imaging

on

the

diagnoses

and

management

of

patients

undergoing

evaluation

for

cognitive

decline

Patients

were

recruited

to

participate

at

clinical

sites

The

site

physician

provided

a

provisional

diagnosis

an

estimate

of

their

diagnostic

confidence

and

their

plan

for

diagnostic

evaluation

and

management

both

before

and

after

receiving

the

results

from

amyloid

imaging

with

florbetapir

Analyses

compared

the

frequency

of

AD

and

non-AD

diagnoses

plans

for

ancillary

testing

and

intended

patient

management

before

and

after

florbetapir

imaging

A

total

of

patients

participated

in

the

trial

amyloid

positive

amyloid

negative

After

receiving

the

results

of

the

florbetapir

scan

diagnosis

changed

in

or

confidence

intervals

CI

of

cases

and

diagnostic

confidence

increased

by

an

average

of

CI

A

total

of

or

CI

of

cases

had

at

least

change

in

their

management

plan

Intended

cholinesterase

inhibitor

or

memantine

treatment

increased

by

CI

of

all

cases

with

positive

scans

and

decreased

by

CI

of

all

those

with

negative

scans

Among

subjects

who

had

not

yet

undergone

a

completed

work

up

planned

brain

structural

imaging

computed

tomographic/magnetic

resonance

imaging

decreased

by

CI

and

planned

neuropsychological

testing

decreased

by

CI

In

summary

amyloid

imaging

results

altered

physician

's

diagnostic

thinking

intended

testing

and

management

of

patients

undergoing

evaluation

for

cognitive

decline


Title
 Effect of Topical Intranasal Therapy on Epistaxis Frequency in Patients With Hereditary Hemorrhagic Telangiectasia : A Randomized Clinical Trial .

 ABSTRACT GENERAL
 Epistaxis is a major factor negatively affecting quality of life in patients with hereditary hemorrhagic telangiectasia ( HHT ; also known as Osler-Weber-Rendu disease ) . Optimal treatment for HHT-related epistaxis is uncertain .

 ABSTRACT GENERAL
 To determine whether topical therapy with any of 3 drugs with differing mechanisms of action is effective in reducing HHT-related epistaxis .

 ABSTRACT GENERAL
 The North American Study of Epistaxis in HHT was a double-blind , placebo-controlled randomized clinical trial performed at 6 HHT centers of excellence . From August 2011 through March 2014 , there were 121 adult patients who met the clinical criteria for HHT and had experienced HHT-related epistaxis with an Epistaxis Severity Score of at least 3.0 . Follow-up was completed in September 2014 .

 ABSTRACT GENERAL
 Patients received twice-daily nose sprays for 12 weeks with either bevacizumab 1 % ( 4 mg/d ) , estriol 0.1 % ( 0.4 mg/d ) , tranexamic acid 10 % ( 40 mg/d ) , or placebo ( 0.9 % saline ) .

 ABSTRACT GENERAL
 The primary outcome was median weekly epistaxis frequency during weeks 5 through 12 . Secondary outcomes included median duration of epistaxis during weeks 5 through 12 , Epistaxis Severity Score , level of hemoglobin , level of ferritin , need for transfusion , emergency department visits , and treatment failure .

 ABSTRACT GENERAL
 Among the 121 patients who were randomized ( mean age , 52.8 years [ SD , 12.9 years ] ; 44 % women with a median of 7.0 weekly episodes of epistaxis [ interquartile range { IQR } , 3.0-14.0 ] ) , 106 patients completed the study duration for the primary outcome measure ( 43 were women [ 41 % ] ) . Drug therapy did not significantly reduce epistaxis frequency ( P = .97 ) . After 12 weeks of treatment , the median weekly number of bleeding episodes was 7.0 ( IQR , 4.5-10.5 ) for patients in the bevacizumab group , 8.0 ( IQR , 4.0-12.0 ) for the estriol group , 7.5 ( IQR , 3.0-11.0 ) for the tranexamic acid group , and 8.0 ( IQR , 3.0-14.0 ) for the placebo group . No drug treatment was significantly different from placebo for epistaxis duration . All groups had a significant improvement in Epistaxis Severity Score at weeks 12 and 24 . There were no significant differences between groups for hemoglobin level , ferritin level , treatment failure , need for transfusion , or emergency department visits .

 ABSTRACT GENERAL
 Among patients with HHT , there were no significant between-group differences in the use of topical intranasal treatment with bevacizumab vs estriol vs tranexamic acid vs placebo and epistaxis frequency .

 ABSTRACT GENERAL
 clinicaltrials.gov Identifier : NCT01408030 .

Title

Effect

of

Topical

Intranasal

Therapy

on

Epistaxis

Frequency

in

Patients

With

Hereditary

Hemorrhagic

Telangiectasia

A

Randomized

Clinical

Trial

ABSTRACT GENERAL

Epistaxis

is

a

major

factor

negatively

affecting

quality

of

life

in

patients

with

hereditary

hemorrhagic

telangiectasia

HHT

also

known

as

Osler-Weber-Rendu

disease

Optimal

treatment

for

HHT-related

epistaxis

is

uncertain

ABSTRACT GENERAL

To

determine

whether

topical

therapy

with

any

of

drugs

with

differing

mechanisms

of

action

is

effective

in

reducing

HHT-related

epistaxis

ABSTRACT GENERAL

The

North

American

Study

of

Epistaxis

in

HHT

was

a

double-blind

placebo-controlled

randomized

clinical

trial

performed

at

HHT

centers

of

excellence

From

August

through

March

there

were

adult

patients

who

met

the

clinical

criteria

for

HHT

and

had

experienced

HHT-related

epistaxis

with

an

Epistaxis

Severity

Score

of

at

least

Follow-up

was

completed

in

September

ABSTRACT GENERAL

Patients

received

twice-daily

nose

sprays

for

weeks

with

either

bevacizumab

mg/d

estriol

mg/d

tranexamic

acid

mg/d

or

placebo

saline

ABSTRACT GENERAL

The

primary

outcome

was

median

weekly

epistaxis

frequency

during

weeks

through

Secondary

outcomes

included

median

duration

of

epistaxis

during

weeks

through

Epistaxis

Severity

Score

level

of

hemoglobin

level

of

ferritin

need

for

transfusion

emergency

department

visits

and

treatment

failure

ABSTRACT GENERAL

Among

the

patients

who

were

randomized

mean

age

years

SD

years

women

with

a

median

of

weekly

episodes

of

epistaxis

interquartile

range

IQR

patients

completed

the

study

duration

for

the

primary

outcome

measure

were

women

Drug

therapy

did

not

significantly

reduce

epistaxis

frequency

P

After

weeks

of

treatment

the

median

weekly

number

of

bleeding

episodes

was

IQR

for

patients

in

the

bevacizumab

group

IQR

for

the

estriol

group

IQR

for

the

tranexamic

acid

group

and

IQR

for

the

placebo

group

No

drug

treatment

was

significantly

different

from

placebo

for

epistaxis

duration

All

groups

had

a

significant

improvement

in

Epistaxis

Severity

Score

at

weeks

and

There

were

no

significant

differences

between

groups

for

hemoglobin

level

ferritin

level

treatment

failure

need

for

transfusion

or

emergency

department

visits

ABSTRACT GENERAL

Among

patients

with

HHT

there

were

no

significant

between-group

differences

in

the

use

of

topical

intranasal

treatment

with

bevacizumab

vs

estriol

vs

tranexamic

acid

vs

placebo

and

epistaxis

frequency

ABSTRACT GENERAL

clinicaltrials.gov

Identifier


Title
 Cyclin-dependent kinases : initial approaches to exploit a novel therapeutic target .

 ABSTRACT GENERAL
 Cyclin-dependent kinases ( CDKs ) have been recognized as key regulators of cell cycle progression . Alteration and deregulation of CDK activity are pathogenic hallmarks of neoplasia . Therefore , inhibitors or modulators would be of interest to explore as novel therapeutic agents in cancer , as well as other hyperproliferative disorders . Flavopiridol is a semisynthetic flavonoid that emerged from an empirical screening program as a potent antiproliferative agent that mechanistic studies demonstrated to directly inhibit CDKs 1 , 2 , and 4 as a competitive ATP site antagonist . Initial clinical trials have shown that concentrations that inhibit cell proliferation and CDK activity in vitro can be safely achieved in humans , and additional clinical trials will establish its clinical potential . To address the need for additional chemotypes that may serve as lead structures for drugs that would not have the toxicities associated with flavopiridol , compounds with a similar pattern of cell growth inhibitory activity in the National Cancer Institute 's in vitro anticancer drug screen have been recognized by the computer-assisted pattern recognition algorithm COMPARE and then screened for anti-CDK activity in a biochemical screen . The benzodiazepine derivative NSC 664704 ( 7,12-dihydro-indolo [ 3,2-d ] [ 1 ] benzazepin-6 ( 5H ) - one ) was revealed by that approach as a moderately potent ( IC50 0.4 microM ) inhibitor of CDK2 , which in initial experiments shows evidence of causing cell cycle redistribution in living cells . NSC 664704 is , therefore , a candidate for further structural optimization , guided in part by understanding of the ATP-binding site in CDK2 . This approach represents one way of combining empirical screening information with structure-based design to derive novel candidate therapeutic agents directed against an important cellular target .

Title

Cyclin-dependent

kinases

initial

approaches

to

exploit

a

novel

therapeutic

target

ABSTRACT GENERAL

Cyclin-dependent

kinases

CDKs

have

been

recognized

as

key

regulators

of

cell

cycle

progression

Alteration

and

deregulation

of

CDK

activity

are

pathogenic

hallmarks

of

neoplasia

Therefore

inhibitors

or

modulators

would

be

of

interest

to

explore

as

novel

therapeutic

agents

in

cancer

as

well

as

other

hyperproliferative

disorders

Flavopiridol

is

a

semisynthetic

flavonoid

that

emerged

from

an

empirical

screening

program

as

a

potent

antiproliferative

agent

that

mechanistic

studies

demonstrated

to

directly

inhibit

CDKs

and

as

a

competitive

ATP

site

antagonist

Initial

clinical

trials

have

shown

that

concentrations

that

inhibit

cell

proliferation

and

CDK

activity

in

vitro

can

be

safely

achieved

in

humans

and

additional

clinical

trials

will

establish

its

clinical

potential

To

address

the

need

for

additional

chemotypes

that

may

serve

as

lead

structures

for

drugs

that

would

not

have

the

toxicities

associated

with

flavopiridol

compounds

with

a

similar

pattern

of

cell

growth

inhibitory

activity

in

the

National

Cancer

Institute

's

in

vitro

anticancer

drug

screen

have

been

recognized

by

the

computer-assisted

pattern

recognition

algorithm

COMPARE

and

then

screened

for

anti-CDK

activity

in

a

biochemical

screen

The

benzodiazepine

derivative

NSC

one

was

revealed

by

that

approach

as

a

moderately

potent

microM

inhibitor

of

which

in

initial

experiments

shows

evidence

of

causing

cell

cycle

redistribution

in

living

cells

NSC

is

therefore

a

candidate

for

further

structural

optimization

guided

in

part

by

understanding

of

the

ATP-binding

site

in

This

approach

represents

one

way

of

combining

empirical

screening

information

with

structure-based

design

to

derive

novel

candidate

therapeutic

agents

directed

against

an

important

cellular

target


Title
 Trehalose in ophthalmology .

 ABSTRACT GENERAL
 Trehalose , a disaccharide of glucose , is a naturally occurring nontoxic and nonreducing bioactive sugar . Trehalose is synthetized by many organisms when cells are exposed to stressful conditions , including dehydration , heat , oxidation , hypoxia or even anoxia . Although trehalose is not synthesized by mammalian cells , it has recently been demonstrated to have a number of important properties that indicate its utility in humans . Trehalose enables wound healing by protecting cells , especially cell membranes , from oxidative injury and dessication . When the injured cornea is treated with trehalose , corneal inflammation , scar formation and corneal neovascularization are suppressed . In dry eye disease , trehalose decreased cell apoptosis and reduced oxidative , inflammatory and proteolytic activity at the ocular surface . In UVB irradiated cornea , trehalose suppressed photodamage evoked by UVB rays . It decreased the intracorneal inflammation and reduced corneal neovascularization . Trehalose prevented postoperative fibrous scar formation after ocular surgery , such as glaucoma filtration surgery . The non-toxicity of trehalose allows its administration in humans for extended periods and enables its use in various disease states .

Title

Trehalose

in

ophthalmology

ABSTRACT GENERAL

Trehalose

a

disaccharide

of

glucose

is

a

naturally

occurring

nontoxic

and

nonreducing

bioactive

sugar

Trehalose

is

synthetized

by

many

organisms

when

cells

are

exposed

to

stressful

conditions

including

dehydration

heat

oxidation

hypoxia

or

even

anoxia

Although

trehalose

is

not

synthesized

by

mammalian

cells

it

has

recently

been

demonstrated

to

have

a

number

of

important

properties

that

indicate

its

utility

in

humans

Trehalose

enables

wound

healing

by

protecting

cells

especially

cell

membranes

from

oxidative

injury

and

dessication

When

the

injured

cornea

is

treated

with

trehalose

corneal

inflammation

scar

formation

and

corneal

neovascularization

are

suppressed

In

dry

eye

disease

trehalose

decreased

cell

apoptosis

and

reduced

oxidative

inflammatory

and

proteolytic

activity

at

the

ocular

surface

In

UVB

irradiated

cornea

trehalose

suppressed

photodamage

evoked

by

UVB

rays

It

decreased

the

intracorneal

inflammation

and

reduced

corneal

neovascularization

Trehalose

prevented

postoperative

fibrous

scar

formation

after

ocular

surgery

such

as

glaucoma

filtration

surgery

The

non-toxicity

of

trehalose

allows

its

administration

in

humans

for

extended

periods

and

enables

its

use

in

various

disease

states


Title
 Therapeutic response to benzodiazepine in panic disorder subtypes .

 ABSTRACT BACKGROUND
 This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam , a benzodiazepine .

 ABSTRACT OBJECTIVE
 To evaluate the clinical efficacy of clonazepam in a fixed dosage ( 2 mg/day ) , compared to placebo , in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes .

 ABSTRACT METHODS
 Randomized study with clonazepam and placebo .

 ABSTRACT METHODS
 Outpatient Anxiety and Depression Unit of the Institute of Psychiatry , Universidade Federal do Rio de Janeiro , Rio de Janeiro , Brazil .

 ABSTRACT METHODS
 34 patients with a diagnosis of panic disorder with agoraphobia , between 18 and 55 years old .

 ABSTRACT METHODS
 Administration of clonazepam or placebo for 6 weeks , in panic disorder patients , after they were classified within two subtypes of panic disorder : respiratory and non-respiratory .

 ABSTRACT METHODS
 Changes in the number of panic attacks in comparison with the period before the beginning of the study ; Hamilton Anxiety Scale ; Global Clinical Impression Scale ; and Patient 's Global Impression scale .

 ABSTRACT RESULTS
 In the group that received clonazepam , by the end of the 6th week there was a statistically significant clinical improvement , shown by the remission of panic attacks ( p < 0.001 ) and decrease in anxiety ( p = 0.024 ) . In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder , regarding the therapeutic response to clonazepam .

 ABSTRACT CONCLUSIONS
 Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder , suggesting there is no difference in the therapeutic response between the two subtypes .

Title

Therapeutic

response

to

benzodiazepine

in

panic

disorder

subtypes

ABSTRACT BACKGROUND

This

study

makes

a

comparison

between

two

subtypes

of

panic

disorder

regarding

the

clinical

efficacy

of

clonazepam

a

benzodiazepine

ABSTRACT OBJECTIVE

To

evaluate

the

clinical

efficacy

of

clonazepam

in

a

fixed

dosage

mg/day

compared

to

placebo

in

the

treatment

of

panic

disorder

patients

and

to

verify

whether

there

are

any

differences

in

the

responses

to

clonazepam

between

panic

disorder

patients

with

the

respiratory

and

non-respiratory

subtypes

ABSTRACT METHODS

Randomized

study

with

clonazepam

and

placebo

ABSTRACT METHODS

Outpatient

Anxiety

and

Depression

Unit

of

the

Institute

of

Psychiatry

Universidade

Federal

do

Rio

de

Janeiro

Rio

de

Janeiro

Brazil

ABSTRACT METHODS

patients

with

a

diagnosis

of

panic

disorder

with

agoraphobia

between

and

years

old

ABSTRACT METHODS

Administration

of

clonazepam

or

placebo

for

weeks

in

panic

disorder

patients

after

they

were

classified

within

two

subtypes

of

panic

disorder

respiratory

and

non-respiratory

ABSTRACT METHODS

Changes

in

the

number

of

panic

attacks

in

comparison

with

the

period

before

the

beginning

of

the

study

Hamilton

Anxiety

Scale

Global

Clinical

Impression

Scale

and

Patient

's

Global

Impression

scale

ABSTRACT RESULTS

In

the

group

that

received

clonazepam

by

the

end

of

the

week

there

was

a

statistically

significant

clinical

improvement

shown

by

the

remission

of

panic

attacks

p

and

decrease

in

anxiety

p

In

the

group

that

received

clonazepam

there

was

no

significant

difference

between

the

respiratory

and

non-respiratory

subtypes

of

panic

disorder

regarding

the

therapeutic

response

to

clonazepam

ABSTRACT CONCLUSIONS

Clonazepam

was

equally

effective

in

the

treatment

of

the

respiratory

and

non-respiratory

subtypes

of

panic

disorder

suggesting

there

is

no

difference

in

the

therapeutic

response

between

the

two

subtypes


Title
 Acyclovir in herpes keratitis .

 ABSTRACT GENERAL
 Herpes simplex keratitis accounts for 50 percent of patients presenting at our corneal clinic . Studies of the use of acyclovir in dendritic and geographic ulceration and disciform keratitis are presented . In a double-blind study of acyclovir and idoxuridine in 60 patients with dendritic keratitis , acyclovir was shown to be superior and produced no serious side effects . Patients with geographic ulcers have been treated on an open basis with acyclovir and the drug was found to be effective . A combination of acyclovir and dilute steroid drops appeared to be as effective as currently available treatments in the management of disciform keratitis . Double-blind studies are now in progress to evaluate acyclovir in geographic and disciform keratitis .

Title

Acyclovir

in

herpes

keratitis

ABSTRACT GENERAL

Herpes

simplex

keratitis

accounts

for

percent

of

patients

presenting

at

our

corneal

clinic

Studies

of

the

use

of

acyclovir

in

dendritic

and

geographic

ulceration

and

disciform

keratitis

are

presented

In

a

double-blind

study

of

acyclovir

and

idoxuridine

in

patients

with

dendritic

keratitis

acyclovir

was

shown

to

be

superior

and

produced

no

serious

side

effects

Patients

with

geographic

ulcers

have

been

treated

on

an

open

basis

with

acyclovir

and

the

drug

was

found

to

be

effective

A

combination

of

acyclovir

and

dilute

steroid

drops

appeared

to

be

as

effective

as

currently

available

treatments

in

the

management

of

disciform

keratitis

Double-blind

studies

are

now

in

progress

to

evaluate

acyclovir

in

geographic

and

disciform

keratitis


Title
 Association of baseline disease and patient characteristics with response to etoricoxib and indomethacin for acute gout .

 ABSTRACT OBJECTIVE
 Disease history and clinical features can influence treatment response in patients with acute gout . The purpose of this pooled subgroup analysis was to assess the association of baseline disease and patient characteristics with response to treatment in acute gout using data from two identical studies .

 ABSTRACT METHODS
 Patients > or = 18 years of age with onset of acute gout within 48 h associated with moderate , severe , or extreme pain involving less than four joints were eligible for inclusion in the primary studies , and were randomized to etoricoxib 120 mg once daily ( N = 178 ) or indomethacin 50 mg three times daily ( N = 161 ) . The primary and secondary efficacy endpoints were analyzed using an analysis of covariance model to detect potential differential treatment responses across several subgroups : joint involvement ( mono-articular vs. oligo-articular ) , baseline pain severity ( moderate vs. severe ) , concomitant allopurinol and/or colchicine use ( users vs. nonusers ) , age ( < 45 , 45-55 , and > 55 years ) , gender , and race ( white or other ) .

 ABSTRACT RESULTS
 Overall , etoricoxib and indomethacin demonstrated comparable efficacy across all subgroups . Compared with patients with oligo-articular disease , those with mono-articular disease had significantly greater improvements in patient assessment of pain , patient global assessment of response to therapy ( PGART ) , investigator global assessment of response to therapy ( IGART ) , and study joint tenderness ( p < 0.001 for all ) . Greater improvements were seen in patient assessment of pain ( p < 0.001 ) and study joint tenderness ( p < 0.05 ) for severe/extreme baseline pain compared with moderate baseline pain . Concomitant use of colchicine and/or allopurinol was associated with significantly worse IGART ( p < 0.05 ) .

 ABSTRACT CONCLUSIONS
 This pooled subgroup analysis demonstrated significantly greater response of acute gout to either etoricoxib or indomethacin among those with monoarticular disease , severe/extreme baseline pain , and non-use of colchicine and/or allopurinol . These results should be interpreted in the context of a pooled subgroup analysis with a limited sample size , and with the understanding that associations identified in such analyses do not define causation . Despite limitations , the results provide insights into the types of patients more likely to respond better to anti-inflammatory medication , and reiterate the importance of earlier effective control of the disease .

Title

Association

of

baseline

disease

and

patient

characteristics

with

response

to

etoricoxib

and

indomethacin

for

acute

gout

ABSTRACT OBJECTIVE

Disease

history

and

clinical

features

can

influence

treatment

response

in

patients

with

acute

gout

The

purpose

of

this

pooled

subgroup

analysis

was

to

assess

the

association

of

baseline

disease

and

patient

characteristics

with

response

to

treatment

in

acute

gout

using

data

from

two

identical

studies

ABSTRACT METHODS

Patients

or

years

of

age

with

onset

of

acute

gout

within

h

associated

with

moderate

severe

or

extreme

pain

involving

less

than

four

joints

were

eligible

for

inclusion

in

the

primary

studies

and

were

randomized

to

etoricoxib

mg

once

daily

N

or

indomethacin

mg

three

times

daily

N

The

primary

and

secondary

efficacy

endpoints

were

analyzed

using

an

analysis

of

covariance

model

to

detect

potential

differential

treatment

responses

across

several

subgroups

joint

involvement

mono-articular

vs.

oligo-articular

baseline

pain

severity

moderate

vs.

severe

concomitant

allopurinol

and/or

colchicine

use

users

vs.

nonusers

age

and

years

gender

and

race

white

or

other

ABSTRACT RESULTS

Overall

etoricoxib

and

indomethacin

demonstrated

comparable

efficacy

across

all

subgroups

Compared

with

patients

with

oligo-articular

disease

those

with

mono-articular

disease

had

significantly

greater

improvements

in

patient

assessment

of

pain

patient

global

assessment

of

response

to

therapy

PGART

investigator

global

assessment

of

response

to

therapy

IGART

and

study

joint

tenderness

p

for

all

Greater

improvements

were

seen

in

patient

assessment

of

pain

p

and

study

joint

tenderness

p

for

severe/extreme

baseline

pain

compared

with

moderate

baseline

pain

Concomitant

use

of

colchicine

and/or

allopurinol

was

associated

with

significantly

worse

IGART

p

ABSTRACT CONCLUSIONS

This

pooled

subgroup

analysis

demonstrated

significantly

greater

response

of

acute

gout

to

either

etoricoxib

or

indomethacin

among

those

with

monoarticular

disease

severe/extreme

baseline

pain

and

non-use

of

colchicine

and/or

allopurinol

These

results

should

be

interpreted

in

the

context

of

a

pooled

subgroup

analysis

with

a

limited

sample

size

and

with

the

understanding

that

associations

identified

in

such

analyses

do

not

define

causation

Despite

limitations

the

results

provide

insights

into

the

types

of

patients

more

likely

to

respond

better

to

anti-inflammatory

medication

and

reiterate

the

importance

of

earlier

effective

control

of

the

disease


Title
 Clinical evaluation of sustained-release metronidazole gel versus metronidazole solution as an intracanal medicament in abscessed primary molars .

 ABSTRACT OBJECTIVE
 To evaluate the efficacy of metronidazole gel versus metronidazole solution against Enterococcus faecalis in abscessed primary molars .

 ABSTRACT METHODS
 A clinical trial .

 ABSTRACT METHODS
 Twenty pulpally involved non-vital carious human primary mandibular second molars with furcal abscess were randomly allocated into two groups to evaluate the efficacy of metronidazole gel ( 3 % w/v ) and metronidazole solution ( 0.5 % w/v ) against E. faecalis . Subjects in the first experimental group were subjected to treatment with metronidazole gel ( 3 % w/v ) and subjects in the second experimental group were treated with metronidazole solution ( 0.5 % w/v ) . Two microbial samples ( pre-operative and post-operative samples ) were obtained from the root canals of each subject from both the groups ; sub cultured and efficacy of both the groups were evaluated .

 ABSTRACT RESULTS
 Overall percentage reduction of the mean colony forming unit ( CFU ) count of metronidazole gel ( 3 % w/v ) group was 96.39 % and metronidazole solution ( 0.5 % w/v ) was 90.90 % . Results of intergroup t test of the percentage difference of mean CFU counts between both the groups revealed a statistically highly significant difference , i.e. p value -- 0.008 ( p < 0.01 ) .

 ABSTRACT CONCLUSIONS
 Metronidazole gel ( 3 % w/v ) was more effective than metronidazole solution ( 0.5 % w/v ) against E. faecalis .

Title

Clinical

evaluation

of

sustained-release

metronidazole

gel

versus

metronidazole

solution

as

an

intracanal

medicament

in

abscessed

primary

molars

ABSTRACT OBJECTIVE

To

evaluate

the

efficacy

of

metronidazole

gel

versus

metronidazole

solution

against

Enterococcus

faecalis

in

abscessed

primary

molars

ABSTRACT METHODS

A

clinical

trial

ABSTRACT METHODS

Twenty

pulpally

involved

non-vital

carious

human

primary

mandibular

second

molars

with

furcal

abscess

were

randomly

allocated

into

two

groups

to

evaluate

the

efficacy

of

metronidazole

gel

w/v

and

metronidazole

solution

w/v

against

E.

faecalis

Subjects

in

the

first

experimental

group

were

subjected

to

treatment

with

metronidazole

gel

w/v

and

subjects

in

the

second

experimental

group

were

treated

with

metronidazole

solution

w/v

Two

microbial

samples

pre-operative

and

post-operative

samples

were

obtained

from

the

root

canals

of

each

subject

from

both

the

groups

sub

cultured

and

efficacy

of

both

the

groups

were

evaluated

ABSTRACT RESULTS

Overall

percentage

reduction

of

the

mean

colony

forming

unit

CFU

count

of

metronidazole

gel

w/v

group

was

and

metronidazole

solution

w/v

was

Results

of

intergroup

t

test

of

the

percentage

difference

of

mean

CFU

counts

between

both

the

groups

revealed

a

statistically

highly

significant

difference

i.e.

p

value

p

ABSTRACT CONCLUSIONS

Metronidazole

gel

w/v

was

more

effective

than

metronidazole

solution

w/v

against

E.

faecalis


Title
 Effects of 12-month tadalafil therapy for erectile dysfunction on couple relationships : results from the DETECT study .

 ABSTRACT BACKGROUND
 Erectile dysfunction ( ED ) is distressing and can affect a couple 's relationship .

 ABSTRACT OBJECTIVE
 To investigate partner awareness of ED , relationship problems , and the effects of tadalafil treatment over 12 months .

 ABSTRACT METHODS
 The Determinants of Continued Use of Tadalafil study is a prospective 12-month European observational study in patients with ED initiating or changing treatment to on-demand tadalafil . A total of 1,900 patients were enrolled in eight countries . Assessments were made on predefined treatment outcomes in a routine clinical setting .

 ABSTRACT METHODS
 At baseline , 1 , 6 , and 12 months , patients were asked about relationship problems ( unspecified ) , partner awareness and support of consultation , and partner sexual problems . Data were analyzed for patients continuing tadalafil at 12 months .

 ABSTRACT RESULTS
 At baseline , 96 % of patients had a partner , 80 % of partners supported an ED consult , and 73 % were aware of the consultation . Relationship problems were reported by 17 % of patients at baseline . At 12 months , 84 % of patients were still taking tadalafil . Of these , 19 % reported relationship problems at baseline . After 12 months of treatment with tadalafil , 4 % of patients still reported perceived problems . Factors associated with no relationship problems at 12 months were : at baseline , no previous ED treatment , partner in poor health ; and at 12 months a lower ED severity . If the partner was felt to have a sexual problem at 12 months , relationship improvement was less likely . Further , 3 % of patients developed relationship problems during treatment . Factors associated with developing a relationship problem were : a history of pelvic surgery at baseline , a different partner at 12 months than at baseline , and a partner with a sexual problem at 12 months .

 ABSTRACT CONCLUSIONS
 Improvement of ED with tadalafil was associated with reduced relationship problems , suggesting that problems were associated with ED and resolved with treatment .

Title

Effects

of

tadalafil

therapy

for

erectile

dysfunction

on

couple

relationships

results

from

the

DETECT

study

ABSTRACT BACKGROUND

Erectile

dysfunction

ED

is

distressing

and

can

affect

a

couple

's

relationship

ABSTRACT OBJECTIVE

To

investigate

partner

awareness

of

ED

relationship

problems

and

the

effects

of

tadalafil

treatment

over

months

ABSTRACT METHODS

The

Determinants

of

Continued

Use

of

Tadalafil

study

is

a

prospective

European

observational

study

in

patients

with

ED

initiating

or

changing

treatment

to

on-demand

tadalafil

A

total

of

patients

were

enrolled

in

eight

countries

Assessments

were

made

on

predefined

treatment

outcomes

in

a

routine

clinical

setting

ABSTRACT METHODS

At

baseline

and

months

patients

were

asked

about

relationship

problems

unspecified

partner

awareness

and

support

of

consultation

and

partner

sexual

problems

Data

were

analyzed

for

patients

continuing

tadalafil

at

months

ABSTRACT RESULTS

At

baseline

of

patients

had

a

partner

of

partners

supported

an

ED

consult

and

were

aware

of

the

consultation

Relationship

problems

were

reported

by

of

patients

at

baseline

At

months

of

patients

were

still

taking

tadalafil

Of

these

reported

relationship

problems

at

baseline

After

months

of

treatment

with

tadalafil

of

patients

still

reported

perceived

problems

Factors

associated

with

no

relationship

problems

at

months

were

at

baseline

no

previous

ED

treatment

partner

in

poor

health

and

at

months

a

lower

ED

severity

If

the

partner

was

felt

to

have

a

sexual

problem

at

months

relationship

improvement

was

less

likely

Further

of

patients

developed

relationship

problems

during

treatment

Factors

associated

with

developing

a

relationship

problem

were

a

history

of

pelvic

surgery

at

baseline

a

different

partner

at

months

than

at

baseline

and

a

partner

with

a

sexual

problem

at

months

ABSTRACT CONCLUSIONS

Improvement

of

ED

with

tadalafil

was

associated

with

reduced

relationship

problems

suggesting

that

problems

were

associated

with

ED

and

resolved

with

treatment


Title
 Stem Cell Therapy in Nonneovascular Age-Related Macular Degeneration .

 ABSTRACT GENERAL
 Age-related macular degeneration ( ARMD ) is the leading cause of blindness in subjects older than 50 years of age in the developed world . There are two types of ARMD , neovascular ( NV ) and nonneovascular ( NN ) . While anti-VEGF-based therapies have significantly decreased the visual morbidity associated with NV-ARMD , there are no effective treatments for NN-ARMD . A detailed discussion of NV-ARMD and related therapies is the topic of another section of this special supplement . This review will focus mainly on NN-ARMD . Vision loss in nonneovascular ARMD is highly correlated with the loss of RPE cells and areas of geographic atrophy ( GA ) . Pilot studies using subretinal transplantation of autologous or allogeneic RPE during the past 20 to 30 years have demonstrated that stem cell-derived RPE have the potential to rescue photoreceptor function and restore vision . New methods of differentiating RPE from human embryonic stem cells ( hESC ) and induced pluripotent stem cells ( iPSC ) have created a potentially unlimited supply of RPE cells to meet the demands of future commercially viable stem cell products . Thanks to fundamental advances in stem cell biology , vitreoretinal surgery , and noninvasive retinal imaging , stem cell-based therapies for NN-ARMD are emerging and several clinical trials are in progress . However , there are major regulatory , safety , and technical challenges that remain . This review will focus on summarizing the most promising aspects of stem cell-based therapy for NN-ARMD and highlighting areas that require further research .

Title

Stem

Cell

Therapy

in

Nonneovascular

Age-Related

Macular

Degeneration

ABSTRACT GENERAL

Age-related

macular

degeneration

ARMD

is

the

leading

cause

of

blindness

in

subjects

older

than

years

of

age

in

the

developed

world

There

are

two

types

of

ARMD

neovascular

NV

and

nonneovascular

NN

While

anti-VEGF-based

therapies

have

significantly

decreased

the

visual

morbidity

associated

with

NV-ARMD

there

are

no

effective

treatments

for

NN-ARMD

A

detailed

discussion

of

NV-ARMD

and

related

therapies

is

the

topic

of

another

section

of

this

special

supplement

This

review

will

focus

mainly

on

NN-ARMD

Vision

loss

in

nonneovascular

ARMD

is

highly

correlated

with

the

loss

of

RPE

cells

and

areas

of

geographic

atrophy

GA

Pilot

studies

using

subretinal

transplantation

of

autologous

or

allogeneic

RPE

during

the

past

to

years

have

demonstrated

that

stem

cell-derived

RPE

have

the

potential

to

rescue

photoreceptor

function

and

restore

vision

New

methods

of

differentiating

RPE

from

human

embryonic

stem

cells

hESC

and

induced

pluripotent

stem

cells

iPSC

have

created

a

potentially

unlimited

supply

of

RPE

cells

to

meet

the

demands

of

future

commercially

viable

stem

cell

products

Thanks

to

fundamental

advances

in

stem

cell

biology

vitreoretinal

surgery

and

noninvasive

retinal

imaging

stem

cell-based

therapies

for

NN-ARMD

are

emerging

and

several

clinical

trials

are

in

progress

However

there

are

major

regulatory

safety

and

technical

challenges

that

remain

This

review

will

focus

on

summarizing

the

most

promising

aspects

of

stem

cell-based

therapy

for

NN-ARMD

and

highlighting

areas

that

require

further

research


Title
 Brief intervention for harm reduction with alcohol-positive older adolescents in a hospital emergency department .

 ABSTRACT GENERAL
 This study evaluated the use of a brief motivational interview ( MI ) to reduce alcohol-related consequences and use among adolescents treated in an emergency room ( ER ) following an alcohol-related event . Patients aged 18 to 19 years ( N = 94 ) were randomly assigned to receive either MI or standard care ( SC ) . Assessment and intervention were conducted in the ER during or after the patient 's treatment . Follow-up assessments showed that patients who received the MI had a significantly lower incidence of drinking and driving , traffic violations , alcohol-related injuries , and alcohol-related problems than patients who received SC . Both conditions showed reduced alcohol consumption . The harm-reduction focus of the MI was evident in that MI reduced negative outcomes related to drinking , beyond what was produced by the precipitating event plus SC alone .

Title

Brief

intervention

for

harm

reduction

with

alcohol-positive

older

adolescents

in

a

hospital

emergency

department

ABSTRACT GENERAL

This

study

evaluated

the

use

of

a

brief

motivational

interview

MI

to

reduce

alcohol-related

consequences

and

use

among

adolescents

treated

in

an

emergency

room

ER

following

an

alcohol-related

event

Patients

aged

to

years

N

were

randomly

assigned

to

receive

either

MI

or

standard

care

SC

Assessment

and

intervention

were

conducted

in

the

ER

during

or

after

the

patient

's

treatment

Follow-up

assessments

showed

that

patients

who

received

the

MI

had

a

significantly

lower

incidence

of

drinking

and

driving

traffic

violations

alcohol-related

injuries

and

alcohol-related

problems

than

patients

who

received

SC

Both

conditions

showed

reduced

alcohol

consumption

The

harm-reduction

focus

of

the

MI

was

evident

in

that

MI

reduced

negative

outcomes

related

to

drinking

beyond

what

was

produced

by

the

precipitating

event

plus

SC

alone


Title
 First-line Nivolumab Plus Ipilimumab vs Sunitinib for Metastatic Renal Cell Carcinoma : A Cost-effectiveness Analysis .

 ABSTRACT UNASSIGNED
 Recently , new drugs have been approved for the first-line treatment of metastatic renal cell carcinoma ( mRCC ) . Nivolumab plus ipilimumab significantly increases overall survival for intermediate - and poor-risk patients with mRCC . However , considering the high cost of nivolumab plus ipilimumab , there is a need to assess its value by considering both efficacy and cost .

 ABSTRACT UNASSIGNED
 To evaluate the cost-effectiveness of nivolumab plus ipilimumab vs sunitinib in the first-line setting for intermediate - and poor-risk patients with mRCC from the US payer perspective .

 ABSTRACT UNASSIGNED
 A Markov model was developed to compare the lifetime cost and effectiveness of nivolumab plus ipilimumab vs sunitinib in the first-line treatment of mRCC using outcomes data from the CheckMate 214 phase 3 randomized clinical trial , which included 1096 patients with mRCC ( median age , 62 years ) and compared nivolumab plus ipilimumab vs sunitinib as first-line treatment of mRCC . In the analysis , patients were modeled to receive sunitinib or nivolumab plus ipilimumab for 4 doses followed by nivolumab monotherapy .

 ABSTRACT UNASSIGNED
 Life-years , quality-adjusted life-years ( QALYs ) , and lifetime costs were estimated , at a willingness-to-pay threshold of $ 100 000 to $ 150 000 per QALY . Univariable , 2-way , and probabilistic sensitivity analyses were performed to evaluate the model uncertainty . Additional subgroup analyses were performed .

 ABSTRACT UNASSIGNED
 Nivolumab plus ipilimumab provided an additional 0.96 QALYs , at a cost of $ 108 363 per QALY . Sensitivity analyses found the results to be most sensitive to overall survival hazard ratio ( 0.63 ; 95 % CI , 0.44-0.89 ) and mean patient weight ( 70 kg , range , 40-200 kg ) . Other variables , such as the cost of nivolumab plus ipilimumab ( mean , $ 32 213.44 ; range , $ 25 770.75 - $ 38 656.13 ) , utility values for nivolumab plus ipilimumab ( mean , 0.82 ; range , 0.65-0.98 ) , and proportion receiving nivolumab in sunitinib arm ( mean , 0.27 ; range , 0.22-0.32 ) , had a moderate or minor influence on model results . Subgroup analyses demonstrated that nivolumab plus ipilimumab was most cost-effective for patients with programmed cell death 1 ligand 1 expression of at least 1 % ( $ 86 390 per QALY ) .

 ABSTRACT UNASSIGNED
 In this model , nivolumab plus ipilimumab was estimated to be cost-effective compared with sunitinib for intermediate - and poor-risk patients with mRCC at a willingness-to-pay threshold from $ 100 000 to $ 150 000 per QALY .

Title

First-line

Nivolumab

Plus

Ipilimumab

vs

Sunitinib

for

Metastatic

Renal

Cell

Carcinoma

A

Cost-effectiveness

Analysis

ABSTRACT UNASSIGNED

Recently

new

drugs

have

been

approved

for

the

first-line

treatment

of

metastatic

renal

cell

carcinoma

mRCC

Nivolumab

plus

ipilimumab

significantly

increases

overall

survival

for

intermediate

and

poor-risk

patients

with

mRCC

However

considering

the

high

cost

of

nivolumab

plus

ipilimumab

there

is

a

need

to

assess

its

value

by

considering

both

efficacy

and

cost

ABSTRACT UNASSIGNED

To

evaluate

the

cost-effectiveness

of

nivolumab

plus

ipilimumab

vs

sunitinib

in

the

first-line

setting

for

intermediate

and

poor-risk

patients

with

mRCC

from

the

US

payer

perspective

ABSTRACT UNASSIGNED

A

Markov

model

was

developed

to

compare

the

lifetime

cost

and

effectiveness

of

nivolumab

plus

ipilimumab

vs

sunitinib

in

the

first-line

treatment

of

mRCC

using

outcomes

data

from

the

CheckMate

phase

randomized

clinical

trial

which

included

patients

with

mRCC

median

age

years

and

compared

nivolumab

plus

ipilimumab

vs

sunitinib

as

first-line

treatment

of

mRCC

In

the

analysis

patients

were

modeled

to

receive

sunitinib

or

nivolumab

plus

ipilimumab

for

doses

followed

by

nivolumab

monotherapy

ABSTRACT UNASSIGNED

Life-years

quality-adjusted

life-years

QALYs

and

lifetime

costs

were

estimated

at

a

willingness-to-pay

threshold

of

100 000

to

150 000

per

QALY

Univariable

and

probabilistic

sensitivity

analyses

were

performed

to

evaluate

the

model

uncertainty

Additional

subgroup

analyses

were

performed

ABSTRACT UNASSIGNED

Nivolumab

plus

ipilimumab

provided

an

additional

QALYs

at

a

cost

of

108 363

per

QALY

Sensitivity

analyses

found

the

results

to

be

most

sensitive

to

overall

survival

hazard

ratio

CI

and

mean

patient

weight

kg

range

kg

Other

variables

such

as

the

cost

of

nivolumab

plus

ipilimumab

mean

32 213.44

range

25 770.75

38 656.13

utility

values

for

nivolumab

plus

ipilimumab

mean

range

and

proportion

receiving

nivolumab

in

sunitinib

arm

mean

range

had

a

moderate

or

minor

influence

on

model

results

Subgroup

analyses

demonstrated

that

nivolumab

plus

ipilimumab

was

most

cost-effective

for

patients

with

programmed

cell

death

ligand

expression

of

at

least

86 390

per

QALY

ABSTRACT UNASSIGNED

In

this

model

nivolumab

plus

ipilimumab

was

estimated

to

be

cost-effective

compared

with

sunitinib

for

intermediate

and

poor-risk

patients

with

mRCC

at

a

willingness-to-pay

threshold

from

100 000

to

150 000

per

QALY


Title
 Inhaled nitric oxide in infants referred for extracorporeal membrane oxygenation : dose response .

 ABSTRACT GENERAL
 To determine the role of inhaled nitric oxide ( NO ) in a population of critically ill hypoxic near-term infants and to determine the dose response to inhaled NO , we examined a consecutive group of 23 infants referred for neonatal extracorporeal membrane oxygenation ( ECMO ) who had an oxygen index of 20 or greater after treatment with bovine surfactant . Inhaled NO was administered in concentrations from 5 to 80 ppm in random order to 23 infants . Overall , 13 infants had a significant response ( an improvement in arterial oxygen pressure > 10 mm Hg or arterial oxygen saturation > 10 % ) to the first administration of inhaled NO , and one infant had a late response . There was no significant difference in the response to inhaled NO as measured by changes in arterial oxygen pressure or in the alveolar-arterial difference in partial pressure of oxygen , for any of the doses from 5 to 80 ppm . Thirteen infants had echocardiographic evidence of persisted pulmonary hypertension ; 11 of these infants responded , compared with 3 responders among the 10 infants without persistent pulmonary hypertension of the newborn ( p < 0.01 ) . Overall , 11 infants required ECMO ; there were two deaths in this group . Seven infants had congenital diaphragmatic hernia ; five of those had a response to NO inhalation and four required ECMO . Our study demonstrates that there is no significant difference in response between low and high doses of inhaled NO and that this treatment may prevent the need for ECMO in some infants referred for this therapy , especially in infants with pulmonary hypertension . Prospective , controlled , randomized , and blinded trials of low doses of inhaled NO are needed to determine the clinical role of this potentially useful therapy .

Title

Inhaled

nitric

oxide

in

infants

referred

for

extracorporeal

membrane

oxygenation

dose

response

ABSTRACT GENERAL

To

determine

the

role

of

inhaled

nitric

oxide

NO

in

a

population

of

critically

ill

hypoxic

near-term

infants

and

to

determine

the

dose

response

to

inhaled

NO

we

examined

a

consecutive

group

of

infants

referred

for

neonatal

extracorporeal

membrane

oxygenation

ECMO

who

had

an

oxygen

index

of

or

greater

after

treatment

with

bovine

surfactant

Inhaled

NO

was

administered

in

concentrations

from

to

ppm

in

random

order

to

infants

Overall

infants

had

a

significant

response

an

improvement

in

arterial

oxygen

pressure

mm

Hg

or

arterial

oxygen

saturation

to

the

first

administration

of

inhaled

NO

and

one

infant

had

a

late

response

There

was

no

significant

difference

in

the

response

to

inhaled

NO

as

measured

by

changes

in

arterial

oxygen

pressure

or

in

the

alveolar-arterial

difference

in

partial

pressure

of

oxygen

for

any

of

the

doses

from

to

ppm

Thirteen

infants

had

echocardiographic

evidence

of

persisted

pulmonary

hypertension

of

these

infants

responded

compared

with

responders

among

the

infants

without

persistent

pulmonary

hypertension

of

the

newborn

p

Overall

infants

required

ECMO

there

were

two

deaths

in

this

group

Seven

infants

had

congenital

diaphragmatic

hernia

five

of

those

had

a

response

to

NO

inhalation

and

four

required

ECMO

Our

study

demonstrates

that

there

is

no

significant

difference

in

response

between

low

and

high

doses

of

inhaled

NO

and

that

this

treatment

may

prevent

the

need

for

ECMO

in

some

infants

referred

for

this

therapy

especially

in

infants

with

pulmonary

hypertension

Prospective

controlled

randomized

and

blinded

trials

of

low

doses

of

inhaled

NO

are

needed

to

determine

the

clinical

role

of

this

potentially

useful

therapy


Title
 Efficacy of interventions targeting household air pollution from residential wood stoves .

 ABSTRACT GENERAL
 Wood is commonly used for residential heating , but there are limited evidence-based interventions for reducing wood smoke exposures in the indoor environment . The Asthma Randomized Trial of Indoor Wood Smoke ( ARTIS ) study was designed to assess the efficacy of residential interventions to reduce indoor PM exposure from wood stoves . As part of a three-arm randomized placebo-controlled trial , two household-level interventions were evaluated : wood stove changeouts and air filtration units . Exposure outcomes included indoor measures such as continuous PM2 .5 , particle counts , and carbon monoxide . Median indoor PM2 .5 concentration was 17.5 μg/m3 in wood-burning homes prior to interventions . No significant reductions in PM2 .5 concentrations were observed in the 40 homes receiving the placebo filter intervention . Sixteen homes received the wood stove changeout and showed no significant changes in PM2 .5 or particle counts . PM2 .5 concentrations were reduced by 68 % in the filter intervention homes . Relative to placebo , air filtration unit homes had an overall PM2 .5 reduction of 63 % ( 95 % CI : 47-75 % ) . Relative to the wood stove changeout , the filtration unit intervention was more efficacious and less expensive , yet compliance issues indicated a need for the evaluation of additional strategies for improving indoor air quality in homes using wood stoves .

Title

Efficacy

of

interventions

targeting

household

air

pollution

from

residential

wood

stoves

ABSTRACT GENERAL

Wood

is

commonly

used

for

residential

heating

but

there

are

limited

evidence-based

interventions

for

reducing

wood

smoke

exposures

in

the

indoor

environment

The

Asthma

Randomized

Trial

of

Indoor

Wood

Smoke

ARTIS

study

was

designed

to

assess

the

efficacy

of

residential

interventions

to

reduce

indoor

PM

exposure

from

wood

stoves

As

part

of

a

three-arm

randomized

placebo-controlled

trial

two

household-level

interventions

were

evaluated

wood

stove

changeouts

and

air

filtration

units

Exposure

outcomes

included

indoor

measures

such

as

continuous

particle

counts

and

carbon

monoxide

Median

indoor

concentration

was

in

wood-burning

homes

prior

to

interventions

No

significant

reductions

in

concentrations

were

observed

in

the

homes

receiving

the

placebo

filter

intervention

Sixteen

homes

received

the

wood

stove

changeout

and

showed

no

significant

changes

in

or

particle

counts

concentrations

were

reduced

by

in

the

filter

intervention

homes

Relative

to

placebo

air

filtration

unit

homes

had

an

overall

reduction

of

CI

Relative

to

the

wood

stove

changeout

the

filtration

unit

intervention

was

more

efficacious

and

less

expensive

yet

compliance

issues

indicated

a

need

for

the

evaluation

of

additional

strategies

for

improving

indoor

air

quality

in

homes

using

wood

stoves


Title
 Prostate cancer : Hypofractionated radiotherapy confirmed effective and safe .

Title

Prostate

cancer

Hypofractionated

radiotherapy

confirmed

effective

and

safe


Title
 Hypertension detection and follow-up program . Baseline laboratory examination characteristics of the hypertensive participants .

Title

Hypertension

detection

and

follow-up

program

Baseline

laboratory

examination

characteristics

of

the

hypertensive

participants


Title
 Prospective evaluation of prostate cancer detection by prostate-specific antigen-related parameters .

 ABSTRACT BACKGROUND
 The diagnostic value of prostate-specific antigen ( PSA ) for differentiating prostate cancer from benign prostatic conditions is limited by its lack of specificity . Several PSA-related parameters have been suggested as enhancing the discriminatory power of total PSA values , but their clinical utility should be considered preliminary until established in a prospectively evaluated cohort .

 ABSTRACT METHODS
 In a prospective cohort study , results of ultrasound-guided biopsy and/or transurethral resection of the prostate gland were assessed in 706 consecutive Japanese men . The clinical usefulness of total PSA , free PSA , percentage of free PSA , PSA density ( PSAD ) , PSA density for transition zone ( PSADT ) and gland volume for predicting prostate cancer was investigated using receiver operating characteristic ( ROC ) curve analysis in 16 different patient subgroups .

 ABSTRACT RESULTS
 Overall , 150 of the 706 patients ( 21.2 % ) had prostate carcinoma . The ROC curve analysis showed that PSAD and PSADT were more powerful predictors of prostate cancer than total PSA in most of the 16 patient subgroups tested . The improvement in performance was modest , however . No substantial difference was noted between PSAD and PSADT . Total gland volume did not significantly affect the performance of these parameters . The use of a PSAD threshold value of 0.11-10.15 ng/mL per cm3 ( or a PSADT value of 0.23-0.27 ng/mL per cm3 ) would have avoided 24-48 % ( or , for PSADT , 34-40 % ) of unnecessary biopsies at the cost of missing 5-10 % of detectable cancers in a patient subgroup with intermediate total PSA levels . The performance of free PSA and percentage of free PSA was worse than that of any other test in this study . This may be due to inappropriate handling of sera prior to measurement .

 ABSTRACT CONCLUSIONS
 The discriminatory potential of total PSA for predicting prostate cancer was modestly improved by the use of PSAD and PSADT . No substantial advantage of PSADT over PSAD could be demonstrated . Stringent and standardized storage conditions should always be maintained when applying free PSA-related parameters .

Title

Prospective

evaluation

of

prostate

cancer

detection

by

prostate-specific

antigen-related

parameters

ABSTRACT BACKGROUND

The

diagnostic

value

of

prostate-specific

antigen

PSA

for

differentiating

prostate

cancer

from

benign

prostatic

conditions

is

limited

by

its

lack

of

specificity

Several

PSA-related

parameters

have

been

suggested

as

enhancing

the

discriminatory

power

of

total

PSA

values

but

their

clinical

utility

should

be

considered

preliminary

until

established

in

a

prospectively

evaluated

cohort

ABSTRACT METHODS

In

a

prospective

cohort

study

results

of

ultrasound-guided

biopsy

and/or

transurethral

resection

of

the

prostate

gland

were

assessed

in

consecutive

Japanese

men

The

clinical

usefulness

of

total

PSA

free

PSA

percentage

of

free

PSA

PSA

density

PSAD

PSA

density

for

transition

zone

PSADT

and

gland

volume

for

predicting

prostate

cancer

was

investigated

using

receiver

operating

characteristic

ROC

curve

analysis

in

different

patient

subgroups

ABSTRACT RESULTS

Overall

of

the

patients

had

prostate

carcinoma

The

ROC

curve

analysis

showed

that

PSAD

and

PSADT

were

more

powerful

predictors

of

prostate

cancer

than

total

PSA

in

most

of

the

patient

subgroups

tested

The

improvement

in

performance

was

modest

however

No

substantial

difference

was

noted

between

PSAD

and

PSADT

Total

gland

volume

did

not

significantly

affect

the

performance

of

these

parameters

The

use

of

a

PSAD

threshold

value

of

ng/mL

per

or

a

PSADT

value

of

ng/mL

per

would

have

avoided

or

for

PSADT

of

unnecessary

biopsies

at

the

cost

of

missing

of

detectable

cancers

in

a

patient

subgroup

with

intermediate

total

PSA

levels

The

performance

of

free

PSA

and

percentage

of

free

PSA

was

worse

than

that

of

any

other

test

in

this

study

This

may

be

due

to

inappropriate

handling

of

sera

prior

to

measurement

ABSTRACT CONCLUSIONS

The

discriminatory

potential

of

total

PSA

for

predicting

prostate

cancer

was

modestly

improved

by

the

use

of

PSAD

and

PSADT

No

substantial

advantage

of

PSADT

over

PSAD

could

be

demonstrated

Stringent

and

standardized

storage

conditions

should

always

be

maintained

when

applying

free

PSA-related

parameters


Title
 Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators : two randomised clinical trials .

 ABSTRACT BACKGROUND
 Patients with chronic obstructive pulmonary disease ( COPD ) have few options for treatment . The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD , but not in those concomitantly treated with longacting inhaled bronchodilators . The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated .

 ABSTRACT METHODS
 In two double-blind , multicentre studies done in an outpatient setting , after a 4-week run-in , patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 microg or placebo once a day for 24 weeks , in addition to salmeterol ( M2-127 study ) or tiotropium ( M2-128 study ) . The primary endpoint was change in prebronchodilator forced expiratory volume in 1 s ( FEV ( 1 ) ) . Analysis was by intention to treat . The studies are registered with ClinicalTrials.gov , number NCT00313209 for M2-127 , and NCT00424268 for M2-128 .

 ABSTRACT RESULTS
 In the salmeterol plus roflumilast trial , 466 patients were assigned to and treated with roflumilast and 467 with placebo ; in the tiotropium plus roflumilast trial , 371 patients were assigned to and treated with roflumilast and 372 with placebo . Compared with placebo , roflumilast consistently improved mean prebronchodilator FEV ( 1 ) by 49 mL ( p < 0.0001 ) in patients treated with salmeterol , and 80 mL ( p < 0.0001 ) in those treated with tiotropium . Similar improvement in postbronchodilator FEV ( 1 ) was noted in both groups . Furthermore , roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups . Nausea , diarrhoea , weight loss , and , to a lesser extent , headache were more frequent in patients in the roflumilast groups . These adverse events were associated with increased patient withdrawal .

 ABSTRACT CONCLUSIONS
 Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium , and could become an important treatment for these patients .

 ABSTRACT BACKGROUND
 Nycomed .

Title

Roflumilast

in

moderate-to-severe

chronic

obstructive

pulmonary

disease

treated

with

longacting

bronchodilators

two

randomised

clinical

trials

ABSTRACT BACKGROUND

Patients

with

chronic

obstructive

pulmonary

disease

COPD

have

few

options

for

treatment

The

efficacy

and

safety

of

the

inhibitor

roflumilast

have

been

investigated

in

studies

of

patients

with

moderate-to-severe

COPD

but

not

in

those

concomitantly

treated

with

longacting

inhaled

bronchodilators

The

effect

of

roflumilast

on

lung

function

in

patients

with

COPD

that

is

moderate

to

severe

who

are

already

being

treated

with

salmeterol

or

tiotropium

was

investigated

ABSTRACT METHODS

In

two

double-blind

multicentre

studies

done

in

an

outpatient

setting

after

a

run-in

patients

older

than

years

with

moderate-to-severe

COPD

were

randomly

assigned

to

oral

roflumilast

microg

or

placebo

once

a

day

for

weeks

in

addition

to

salmeterol

study

or

tiotropium

study

The

primary

endpoint

was

change

in

prebronchodilator

forced

expiratory

volume

in

s

FEV

Analysis

was

by

intention

to

treat

The

studies

are

registered

with

ClinicalTrials.gov

number

for

and

for

ABSTRACT RESULTS

In

the

salmeterol

plus

roflumilast

trial

patients

were

assigned

to

and

treated

with

roflumilast

and

with

placebo

in

the

tiotropium

plus

roflumilast

trial

patients

were

assigned

to

and

treated

with

roflumilast

and

with

placebo

Compared

with

placebo

roflumilast

consistently

improved

mean

prebronchodilator

FEV

by

mL

p

in

patients

treated

with

salmeterol

and

mL

p

in

those

treated

with

tiotropium

Similar

improvement

in

postbronchodilator

FEV

was

noted

in

both

groups

Furthermore

roflumilast

had

beneficial

effects

on

other

lung

function

measurements

and

on

selected

patient-reported

outcomes

in

both

groups

Nausea

diarrhoea

weight

loss

and

to

a

lesser

extent

headache

were

more

frequent

in

patients

in

the

roflumilast

groups

These

adverse

events

were

associated

with

increased

patient

withdrawal

ABSTRACT CONCLUSIONS

Roflumilast

improves

lung

function

in

patients

with

COPD

treated

with

salmeterol

or

tiotropium

and

could

become

an

important

treatment

for

these

patients

ABSTRACT BACKGROUND

Nycomed


Title
 [ Clinical efficiency of candesatran depends on angiotension II receptor , type 1 gene polymorphism ] .

 ABSTRACT GENERAL
 Frequency of A and C alleles of the polymorphic gene ( A1166C ) of first type angiotension II receptor in healthy men of Poltava region was 68 % and 32 % accordingly , the AA , AC and CC genotypes made up 51 % ,34 % and 15 % correspondingly . The patients with essential hypertension had the following figures : 44 % and 56 % ; 23 % , 52 % and 25 % accordingly . The presence of C allele has been established to lead to more severe course and an early development of essential hypertension . Candesatran monoterapy is more effective for treatment patients having C allele .

Title

Clinical

efficiency

of

candesatran

depends

on

angiotension

II

receptor

type

gene

polymorphism

ABSTRACT GENERAL

Frequency

of

A

and

C

alleles

of

the

polymorphic

gene

of

first

type

angiotension

II

receptor

in

healthy

men

of

Poltava

region

was

and

accordingly

the

AA

AC

and

CC

genotypes

made

up

and

correspondingly

The

patients

with

essential

hypertension

had

the

following

figures

and

and

accordingly

The

presence

of

C

allele

has

been

established

to

lead

to

more

severe

course

and

an

early

development

of

essential

hypertension

Candesatran

monoterapy

is

more

effective

for

treatment

patients

having

C

allele


Title
 Impaired endothelial antithrombotic activity following short-term interruption of continuous subcutaneous insulin infusion in type 1 diabetic patients .

 ABSTRACT GENERAL
 Review of literature has shown an increased rate of thrombotic complications in diabetic patients with frequent episodes of hyperketonemia . However , the mechanisms by which ketosis promotes vascular disease in diabetic patients are unclear . It was the aim of this study to investigate early changes in haemostatic parameters and oxidative stress markers during the hyperketonemic status which follows the interruption of continuous subcutaneous insulin infusion ( CSII ) in type I diabetic patients . Eight CSII-treated type I diabetic patients underwent a 4-hour pump arrest . Blood glucose , insulin and 3-hydroxybutirate were measured to verify the metabolic response . A vein-occlusive ( VO ) test was performed for the determination of tPA and PAI-1 activities and their antigen levels before and after the CSII arrest . Coagulation factor VII and VIII were evaluated by one-stage PT and PTT method , respectively . TF , vWF , tPA and PAI-1 antigens were determined by ELISA , whereas tPA and PAI-1 activities using chromogenic methods . Plasma malondialdehyde ( MDA ) and protein carbonyl groups ( PCG ) levels were determined by HPLC and spectrophotometry , respectively . After the insulin deprivation phase , post-VO tPA antigen level significantly decreased ( P = 0.0391 ) , whereas TF and post-VO PAI-1 activity and antigen levels significantly increased ( P = 0.0156 and P = 0.0234 , respectively ) . Plasma MDA and PCG levels were 1.88-fold and 1.74-fold higher than baseline values , respectively . In conclusion , the impairment of the fibrinolytic potential and the increases in TF , MDA and PCG levels may enhance the risk of both arterial and venous thrombosis during ketosis . Thus , early detection of hyperketonemia in DM patients could contribute to the prevention of life-threatening vascular events .

Title

Impaired

endothelial

antithrombotic

activity

following

short-term

interruption

of

continuous

subcutaneous

insulin

infusion

in

type

diabetic

patients

ABSTRACT GENERAL

Review

of

literature

has

shown

an

increased

rate

of

thrombotic

complications

in

diabetic

patients

with

frequent

episodes

of

hyperketonemia

However

the

mechanisms

by

which

ketosis

promotes

vascular

disease

in

diabetic

patients

are

unclear

It

was

the

aim

of

this

study

to

investigate

early

changes

in

haemostatic

parameters

and

oxidative

stress

markers

during

the

hyperketonemic

status

which

follows

the

interruption

of

continuous

subcutaneous

insulin

infusion

CSII

in

type

I

diabetic

patients

Eight

CSII-treated

type

I

diabetic

patients

underwent

a

pump

arrest

Blood

glucose

insulin

and

were

measured

to

verify

the

metabolic

response

A

vein-occlusive

VO

test

was

performed

for

the

determination

of

tPA

and

activities

and

their

antigen

levels

before

and

after

the

CSII

arrest

Coagulation

factor

VII

and

VIII

were

evaluated

by

one-stage

PT

and

PTT

method

respectively

TF

vWF

tPA

and

antigens

were

determined

by

ELISA

whereas

tPA

and

activities

using

chromogenic

methods

Plasma

malondialdehyde

MDA

and

protein

carbonyl

groups

PCG

levels

were

determined

by

HPLC

and

spectrophotometry

respectively

After

the

insulin

deprivation

phase

post-VO

tPA

antigen

level

significantly

decreased

P

whereas

TF

and

post-VO

activity

and

antigen

levels

significantly

increased

P

and

P

respectively

Plasma

MDA

and

PCG

levels

were

and

higher

than

baseline

values

respectively

In

conclusion

the

impairment

of

the

fibrinolytic

potential

and

the

increases

in

TF

MDA

and

PCG

levels

may

enhance

the

risk

of

both

arterial

and

venous

thrombosis

during

ketosis

Thus

early

detection

of

hyperketonemia

in

DM

patients

could

contribute

to

the

prevention

of

life-threatening

vascular

events


Title
 Reduced intensity haemopoietic stem-cell transplantation for treatment of non-malignant diseases in children .

 ABSTRACT BACKGROUND
 Transplantation of allogeneic haemopoietic stem cells can cure several non-malignant disorders in children . Transplantation with reduced intensity preparation might achieve the same goals but with less toxicity . We undertook a pilot study to determine engraftment rates , kinetics of engraftment , toxicity , and acute graft-versus-host disease ( GVHD ) associated with a uniform reduced intensity haemopoietic stem-cell transplant ( HSCT ) regimen for children with non-malignant diseases .

 ABSTRACT METHODS
 We studied 13 paediatric patients with non-malignant disorders who underwent reduced intensity HSCT at Children 's Memorial Hospital from January , 2000 , to February , 2004 . Stem-cell sources included unrelated donor , matched-sibling peripheral blood stem cells , and unrelated cord blood . A uniform preparative regimen was used , consisting of fludarabine , busulfan , and anti-thymocyte globulin . Major endpoints were engraftment , transplant-related mortality at day 100 , short-term toxicities , and incidence of acute GVHD .

 ABSTRACT RESULTS
 72 % of evaluable patients achieved full donor engraftment . There was rapid reconstitution of platelets ( median 13.5 days ) and neutrophils ( median 18 days ) . Short-term toxicities were minimal , as seen by a median length of hospital stay of 7 days ( between days 0-100 ) . Incidence of grade II-IV acute GVHD was 8 % . Two patients died before day 100 from underlying disease and viral infection , respectively ( day 100 transplant-related mortality of 15 % ) . The 1-year overall survival was 84 % ( 95 % CI 64-100 ) . Most patients with immunodeficiencies and metabolic disorders had excellent donor engraftment and disease resolution or stabilisation , but most of those with haemoglobinopathies rejected their graft .

 ABSTRACT CONCLUSIONS
 This reduced intensity regimen followed by HSCT provides a good alternative to myeloablative HSCT for children with non-malignant disorders , except for haemoglobinopathies , in which engraftment is poor . Even patients with unrelated donor haemopoietic stem-cell transplants had adequate engraftment with acceptable toxicities .

Title

Reduced

intensity

haemopoietic

stem-cell

transplantation

for

treatment

of

non-malignant

diseases

in

children

ABSTRACT BACKGROUND

Transplantation

of

allogeneic

haemopoietic

stem

cells

can

cure

several

non-malignant

disorders

in

children

Transplantation

with

reduced

intensity

preparation

might

achieve

the

same

goals

but

with

less

toxicity

We

undertook

a

pilot

study

to

determine

engraftment

rates

kinetics

of

engraftment

toxicity

and

acute

graft-versus-host

disease

GVHD

associated

with

a

uniform

reduced

intensity

haemopoietic

stem-cell

transplant

HSCT

regimen

for

children

with

non-malignant

diseases

ABSTRACT METHODS

We

studied

paediatric

patients

with

non-malignant

disorders

who

underwent

reduced

intensity

HSCT

at

Children

's

Memorial

Hospital

from

January

to

February

Stem-cell

sources

included

unrelated

donor

matched-sibling

peripheral

blood

stem

cells

and

unrelated

cord

blood

A

uniform

preparative

regimen

was

used

consisting

of

fludarabine

busulfan

and

anti-thymocyte

globulin

Major

endpoints

were

engraftment

transplant-related

mortality

at

day

short-term

toxicities

and

incidence

of

acute

GVHD

ABSTRACT RESULTS

of

evaluable

patients

achieved

full

donor

engraftment

There

was

rapid

reconstitution

of

platelets

median

days

and

neutrophils

median

days

Short-term

toxicities

were

minimal

as

seen

by

a

median

length

of

hospital

stay

of

days

between

days

Incidence

of

grade

II-IV

acute

GVHD

was

Two

patients

died

before

day

from

underlying

disease

and

viral

infection

respectively

day

transplant-related

mortality

of

The

overall

survival

was

CI

Most

patients

with

immunodeficiencies

and

metabolic

disorders

had

excellent

donor

engraftment

and

disease

resolution

or

stabilisation

but

most

of

those

with

haemoglobinopathies

rejected

their

graft

ABSTRACT CONCLUSIONS

This

reduced

intensity

regimen

followed

by

HSCT

provides

a

good

alternative

to

myeloablative

HSCT

for

children

with

non-malignant

disorders

except

for

haemoglobinopathies

in

which

engraftment

is

poor

Even

patients

with

unrelated

donor

haemopoietic

stem-cell

transplants

had

adequate

engraftment

with

acceptable

toxicities


Title
 May antioxidant therapy improve sperm parameters of men with persistent oligospermia after retrograde embolization for varicocele ?

 ABSTRACT GENERAL
 We performed a randomized , prospective , controlled , intention to treat study in order to determine the effectiveness of an antioxidant therapy in improve the quality of seminal fluid parameters and the natural pregnancies in men with persistent oligospermia ( 5-20 million/ml ) 6 months after retrograde embolization . Forty-two subjects were enrolled and randomized in the study . Treated group ( 20 subjects ) was assigned to receive antioxidant therapy ( NAC 600 mg and vitamins-minerals ) . Untreated group ( 22 subjects ) received no adjunctive medical therapy and was used as controls . Our data were analyzed with an intention to treat strategy . A statistically significant increase in sperm count after antioxidant therapy was recorded ( P = 0.009 ) . After this therapy , no statistical differences in percentage of WHO class A motile sperm ( P = 0.752 ) and typical forms ( P = 0.926 ) were found . The univariate logistic regression analysis showed that a man treated with antioxidant therapy presented a probability to have a normal sperm count 20-fold ( OR = 20.1 ; CI 95 % = 1.05-43.2 ; P = 0.014 ) higher than a man who was untreated . No significant impact on spontaneous pregnancies was found after antioxidant therapy . Despite this preliminary data , we show that antioxidant therapy based on a combination of NAC and micronutrient supplementation can be helpful in improve the sperm count at least in a subset of oligospermic males . However , this improving in sperm count is not associated with a significant increase in spontaneous pregnancies after 12 months .

Title

May

antioxidant

therapy

improve

sperm

parameters

of

men

with

persistent

oligospermia

after

retrograde

embolization

for

varicocele

ABSTRACT GENERAL

We

performed

a

randomized

prospective

controlled

intention

to

treat

study

in

order

to

determine

the

effectiveness

of

an

antioxidant

therapy

in

improve

the

quality

of

seminal

fluid

parameters

and

the

natural

pregnancies

in

men

with

persistent

oligospermia

million/ml

months

after

retrograde

embolization

Forty-two

subjects

were

enrolled

and

randomized

in

the

study

Treated

group

subjects

was

assigned

to

receive

antioxidant

therapy

NAC

mg

and

vitamins-minerals

Untreated

group

subjects

received

no

adjunctive

medical

therapy

and

was

used

as

controls

Our

data

were

analyzed

with

an

intention

to

treat

strategy

A

statistically

significant

increase

in

sperm

count

after

antioxidant

therapy

was

recorded

P

After

this

therapy

no

statistical

differences

in

percentage

of

WHO

class

A

motile

sperm

P

and

typical

forms

P

were

found

The

univariate

logistic

regression

analysis

showed

that

a

man

treated

with

antioxidant

therapy

presented

a

probability

to

have

a

normal

sperm

count

OR

CI

P

higher

than

a

man

who

was

untreated

No

significant

impact

on

spontaneous

pregnancies

was

found

after

antioxidant

therapy

Despite

this

preliminary

data

we

show

that

antioxidant

therapy

based

on

a

combination

of

NAC

and

micronutrient

supplementation

can

be

helpful

in

improve

the

sperm

count

at

least

in

a

subset

of

oligospermic

males

However

this

improving

in

sperm

count

is

not

associated

with

a

significant

increase

in

spontaneous

pregnancies

after

months


Title
 Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis : the ISIS randomized controlled trial .

 ABSTRACT BACKGROUND
 Inhaled hypertonic saline is recommended as therapy for patients 6 years or older with cystic fibrosis ( CF ) , but its efficacy has never been evaluated in patients younger than 6 years with CF.

 ABSTRACT OBJECTIVE
 To determine if hypertonic saline reduces the rate of protocol-defined pulmonary exacerbations in patients younger than 6 years with CF.

 ABSTRACT METHODS
 The Infant Study of Inhaled Saline in Cystic Fibrosis ( ISIS ) , a multicenter , randomized , double-blind , placebo-controlled trial conducted from April 2009 to October 2011 at 30 CF care centers in the United States and Canada . Participants were aged 4 to 60 months and had an established diagnosis of CF. A total of 344 patients were assessed for eligibility ; 321 participants were randomized ; 29 ( 9 % ) withdrew prematurely .

 ABSTRACT METHODS
 The active treatment group ( n = 158 ) received 7 % hypertonic saline and the control group ( n = 163 ) received 0.9 % isotonic saline , nebulized twice daily for 48 weeks . Both groups received albuterol or levalbuterol prior to each study drug dose .

 ABSTRACT METHODS
 Rate during the 48-week treatment period of protocol-defined pulmonary exacerbations treated with oral , inhaled , or intravenous antibiotics .

 ABSTRACT RESULTS
 The mean pulmonary exacerbation rate ( events per person-year ) was 2.3 ( 95 % CI , 2.0-2.5 ) in the active treatment group and 2.3 ( 95 % CI , 2.1-2.6 ) in the control group ; the adjusted rate ratio was 0.98 ( 95 % CI , 0.84-1.15 ) . Among participants with pulmonary exacerbations , the mean number of total antibiotic treatment days for a pulmonary exacerbation was 60 ( 95 % CI , 49-70 ) in the active treatment group and 52 ( 95 % CI , 43-61 ) in the control group . There was no significant difference in secondary end points including height , weight , respiratory rate , oxygen saturation , cough , or respiratory symptom scores . Infant pulmonary function testing performed as an exploratory outcome in a subgroup ( n = 73 , with acceptable measurements at 2 visits in 45 participants ) did not demonstrate significant differences between groups except for the mean change in forced expiratory volume in 0.5 seconds , which was 38 mL ( 95 % CI , 1-76 ) greater in the active treatment group . Adherence determined by returned study drug ampoules was at least 75 % in each group . Adverse event profiles were also similar , with the most common adverse event of moderate or severe severity in each group being cough ( 39 % of active treatment group , 38 % of control group ) .

 ABSTRACT CONCLUSIONS
 Among infants and children younger than 6 years with cystic fibrosis , the use of inhaled hypertonic saline compared with isotonic saline did not reduce the rate of pulmonary exacerbations over the course of 48 weeks of treatment .

 ABSTRACT BACKGROUND
 clinicaltrials.gov Identifier : NCT00709280 .

Title

Inhaled

hypertonic

saline

in

infants

and

children

younger

than

years

with

cystic

fibrosis

the

ISIS

randomized

controlled

trial

ABSTRACT BACKGROUND

Inhaled

hypertonic

saline

is

recommended

as

therapy

for

patients

years

or

older

with

cystic

fibrosis

CF

but

its

efficacy

has

never

been

evaluated

in

patients

younger

than

years

with

CF.

ABSTRACT OBJECTIVE

To

determine

if

hypertonic

saline

reduces

the

rate

of

protocol-defined

pulmonary

exacerbations

in

patients

younger

than

years

with

CF.

ABSTRACT METHODS

The

Infant

Study

of

Inhaled

Saline

in

Cystic

Fibrosis

ISIS

a

multicenter

randomized

double-blind

placebo-controlled

trial

conducted

from

April

to

October

at

CF

care

centers

in

the

United

States

and

Canada

Participants

were

aged

to

months

and

had

an

established

diagnosis

of

CF.

A

total

of

patients

were

assessed

for

eligibility

participants

were

randomized

withdrew

prematurely

ABSTRACT METHODS

The

active

treatment

group

n

received

hypertonic

saline

and

the

control

group

n

received

isotonic

saline

nebulized

twice

daily

for

weeks

Both

groups

received

albuterol

or

levalbuterol

prior

to

each

study

drug

dose

ABSTRACT METHODS

Rate

during

the

treatment

period

of

protocol-defined

pulmonary

exacerbations

treated

with

oral

inhaled

or

intravenous

antibiotics

ABSTRACT RESULTS

The

mean

pulmonary

exacerbation

rate

events

per

person-year

was

CI

in

the

active

treatment

group

and

CI

in

the

control

group

the

adjusted

rate

ratio

was

CI

Among

participants

with

pulmonary

exacerbations

the

mean

number

of

total

antibiotic

treatment

days

for

a

pulmonary

exacerbation

was

CI

in

the

active

treatment

group

and

CI

in

the

control

group

There

was

no

significant

difference

in

secondary

end

points

including

height

weight

respiratory

rate

oxygen

saturation

cough

or

respiratory

symptom

scores

Infant

pulmonary

function

testing

performed

as

an

exploratory

outcome

in

a

subgroup

n

with

acceptable

measurements

at

visits

in

participants

did

not

demonstrate

significant

differences

between

groups

except

for

the

mean

change

in

forced

expiratory

volume

in

seconds

which

was

mL

CI

greater

in

the

active

treatment

group

Adherence

determined

by

returned

study

drug

ampoules

was

at

least

in

each

group

Adverse

event

profiles

were

also

similar

with

the

most

common

adverse

event

of

moderate

or

severe

severity

in

each

group

being

cough

of

active

treatment

group

of

control

group

ABSTRACT CONCLUSIONS

Among

infants

and

children

younger

than

years

with

cystic

fibrosis

the

use

of

inhaled

hypertonic

saline

compared

with

isotonic

saline

did

not

reduce

the

rate

of

pulmonary

exacerbations

over

the

course

of

weeks

of

treatment

ABSTRACT BACKGROUND

clinicaltrials.gov

Identifier