Review article: Risk of cardiovascular events in patients with inflammatory bowel disease receiving small molecule drugs
Alimentary Pharmacology & Therapeutics,
Год журнала:
2023,
Номер
57(11), С. 1231 - 1248
Опубликована: Апрель 10, 2023
Summary
Background
In
the
context
of
an
ageing
inflammatory
bowel
disease
(IBD)
population,
cardiovascular
comorbidities
become
particularly
relevant.
Novel
small
molecule
drugs
(SMDs)
for
treatment
moderate‐to‐severe
IBD
have
been
recently
approved,
including
Janus
kinase
(JAK)
inhibitors
and
sphingosine‐1‐phosphate
receptor
(S1P)
modulators.
Data
from
rheumatoid
arthritis
population
raised
concerns
about
risk
events
with
use
tofacitinib,
which
was
extrapolated
to
other
immune‐mediated
diseases
JAK
inhibitors.
S1P
modulation
has
associated
potential
events,
especially
bradycardia
cardiac
conduction
abnormalities.
Aim
To
review
incidence
SMDs
in
patients
provide
practical
recommendations
on
mitigation
strategies.
Methods
Published
literature
reviewed;
were
synthesised
by
experts
both
IBD.
Results
Evidence
does
not
indicate
a
higher
tofacitinib
The
is
intermediate
high
risk.
modulators
may
be
dose‐dependent,
first‐dose
effect,
transient
abnormalities
(bradycardia
AV
block).
Screening
monitoring
factors
should
done
all
Risk
stratification
performed
before
starting
SMDs.
Conclusions
Available
evidence
indicates
reassuring
safety
profile
perspective
overall
population.
Efforts
made
identify
at
events.
Язык: Английский
Mechanism‐Guided Computational Design of ω‐Transaminase by Reprograming of High‐Energy‐Barrier Steps
Angewandte Chemie International Edition,
Год журнала:
2022,
Номер
61(52)
Опубликована: Окт. 27, 2022
Abstract
ω‐Transaminases
(ω‐TAs)
show
considerable
potential
for
the
synthesis
of
chiral
amines.
However,
their
low
catalytic
efficiency
towards
bulky
substrates
limits
application,
and
complicated
mechanisms
prevent
precise
enzyme
design.
Herein,
we
address
this
challenge
using
a
mechanism‐guided
computational
design
strategy
by
reprograming
transition
ground
states
in
key
reaction
steps.
The
common
features
among
three
high‐energy‐barrier
steps
responsible
were
revealed
quantum
mechanics
(QM).
Five
residues
simultaneously
tailored
to
stabilize
rate‐limiting
state
with
aid
Rosetta
14
top‐ranked
variants
showed
16.9–143‐fold
improved
activity.
best
variant,
M9
(Q25F/M60W/W64F/I266A),
was
significantly
increased,
1660‐fold
increase
k
cat
/
K
m
1.5–26.8‐fold
turnover
number
(TON)
various
indanone
derivatives.
Язык: Английский
The Role of Patient-Reported Outcomes to Measure Treatment Satisfaction in Drug Development
Carolina Navas,
Alexandra Palmer Minton,
Ana Maria Rodriguez-Leboeuf
и другие.
Patient,
Год журнала:
2024,
Номер
17(6), С. 603 - 617
Опубликована: Июль 8, 2024
Treatment
satisfaction
is
a
person's
rating
of
his
or
her
treatment
experience,
including
processes
and
outcomes.
It
directly
related
to
adherence,
which
may
be
predictive
effectiveness
in
clinical
real-world
research.
Consequently,
patient-reported
outcome
(PRO)
instruments
have
been
developed
incorporate
patient
experience
throughout
various
stages
drug
development
routine
care.
PRO
enable
clinicians
researchers
evaluate
compare
data
different
settings.
important
select
fit-for-purpose
that
demonstrated
adequate
levels
reliability,
validity,
sensitivity
change
support
their
use.
Some
these
are
unidimensional
while
some
multidimensional;
generic
can
applied
across
therapeutic
areas,
others
for
use
specific
modality
condition.
This
article
describes
the
role
as
well
regulatory
Health
Technology
Assessment
(HTA)
decision
making
calls
more
widespread
carefully
selected
early-
late-phase
development.
Язык: Английский
Impact of Disease Modifying Therapy on MS-Related Fatigue: A Narrative Review
Brain Sciences,
Год журнала:
2023,
Номер
14(1), С. 4 - 4
Опубликована: Дек. 20, 2023
Multiple
sclerosis
(MS)
is
a
chronic
autoimmune
disease
that
affects
the
central
nervous
system
by
causing
inflammation,
demyelination
and
neurodegeneration.
Fatigue
most
prevalent
one
of
disabling
symptoms
among
people
with
MS
(pwMS).
Due
to
its
complexity
subjective
character,
fatigue
still
little
understood
despite
frequent
occurrence
severe
impact.
The
potential
causes,
effects,
treatments
associated
have
been
extensively
studied
in
recent
years.
Though
benefits
such
variety
contributions
are
obvious,
there
not
many
attempts
evaluate
effect
modifying
therapies
(DMTs)
on
MS-related
fatigue.
In
this
review,
we
summarize
clinical
trials
research
studies,
discuss
different
DMTs
Язык: Английский
Mechanism‐Guided Computational Design of ω‐Transaminase by Reprograming of High‐Energy‐Barrier Steps
Angewandte Chemie,
Год журнала:
2022,
Номер
134(52)
Опубликована: Окт. 27, 2022
Abstract
ω‐Transaminases
(ω‐TAs)
show
considerable
potential
for
the
synthesis
of
chiral
amines.
However,
their
low
catalytic
efficiency
towards
bulky
substrates
limits
application,
and
complicated
mechanisms
prevent
precise
enzyme
design.
Herein,
we
address
this
challenge
using
a
mechanism‐guided
computational
design
strategy
by
reprograming
transition
ground
states
in
key
reaction
steps.
The
common
features
among
three
high‐energy‐barrier
steps
responsible
were
revealed
quantum
mechanics
(QM).
Five
residues
simultaneously
tailored
to
stabilize
rate‐limiting
state
with
aid
Rosetta
14
top‐ranked
variants
showed
16.9–143‐fold
improved
activity.
best
variant,
M9
(Q25F/M60W/W64F/I266A),
was
significantly
increased,
1660‐fold
increase
k
cat
/
K
m
1.5–26.8‐fold
turnover
number
(TON)
various
indanone
derivatives.
Язык: Английский