PCAB Safety: Balancing Potential Long‐Term Risks With Short‐Term Benefits
Alimentary Pharmacology & Therapeutics,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 16, 2025
Potassium-competitive
acid
blockers
(PCABs),
such
as
vonoprazan,
provide
more
rapid,
potent
and
prolonged
suppression
than
proton
pump
inhibitors
(PPIs),
may
offer
advantages
in
the
treatment
of
GERD
other
acid-related
disorders.
PPI-related
adverse
effects,
including
enteric
infection,
pneumonia,
micronutrient
deficiencies,
have
been
attributed
primarily
to
gastric
[1],
which
raises
concerns
that
treatment-emergent
events
(TEAEs)
could
be
profound
with
PCAB
use.
The
current
study
by
Howden
et
al.
[2]
found
vonoprazan
is
well-tolerated,
a
safety
profile
comparable
PPIs.
This
based
on
an
assessment
TEAEs
across
14
clinical
trials
compared
lansoprazole,
esomeprazole
or
placebo,
addition
post-marketing
data
from
2014–2023.
While
short-term
seems
supported,
study's
mean
exposure
duration
142
days
(20
weeks/5
months)
maximum
260
weeks
(5
years)
incomplete
longer-term
profile.
Notably,
several
PPI-associated
can
only
fully
evaluated
after
chronic
exposure,
bone
fracture,
vitamin
B12
deficiency
malignancy.
Bone
fracture
has
associated
PPI
use
at
least
7
years,
but
not
less
6
years
[3];
thus,
this
analysis
sufficient
detect
increased
incidence
fractures.
mechanism
due
calcium
magnesium
malabsorption,
occurs
over
5–10
[4].
Additionally,
while
impact
mineral
density
controversial,
timing
osteoporosis
development
women
exceed
10
[5].
Vitamin
take
3–5
deplete
body,
usually
presenting
no
minimal
symptoms
short
term
additional
decades
manifest
clinically
glossitis,
anaemia
neuropsychiatric
dysfunction
[6],
though
association
between
dementia
remains
controversial
[7].
Gastric
malignancy
often
arises
subacute
process,
median
time
progression
6.1
nondysplastic
intestinal
metaplasia
adenocarcinoma
[8].
Risk
cancer
cumulative
dose
well
longer
therapy
(>
3
[9],
was
inconsistent
studies
involve
various
mechanisms,
H.
pylori
infection
alterations
GI
microbiota
[10].
Of
note,
serious
were
identified
potentially
related
investigators
included
acute
cholangitis,
diverticulitis,
malignancies,
thyroiditis,
atrial
fibrillation
transient
loss
consciousness.
Additional
evaluation
needed
determine
frequency,
causality
potential
mechanisms
action.
Despite
use,
PPIs
remain
mainstay
for
numerous
conditions
because,
ultimately,
absolute
risk
low,
debated,
few
therapeutic
alternatives
exist.
there
yet
long-term
draw
same
conclusions,
we
believe
PCABs
likely
role
conditions,
particularly
those
failed,
future
evaluations
real-world
application
will
clarify
harms
benefits
presently
underappreciated.
Stephanie
Owyang:
conceptualization,
writing
–
original
draft,
review
editing.
Wai-Kit
Lo:
editing,
supervision.
article
linked
al
paper.
To
view
article,
visit
https://doi.org/10.1111/apt.18458.
Data
sharing
applicable
datasets
generated
analysed
during
study.
Язык: Английский
Immediate and delayed hypersensitivity reactions to Proton pump inhibitors: A review article
SANAMED,
Год журнала:
2025,
Номер
00, С. 80 - 80
Опубликована: Янв. 1, 2025
Proton
pump
inhibitors
(PPIs)
are
among
the
most
widely
prescribed
medications
in
clinical
practice,
primarily
used
for
managing
acid-related
gastrointestinal
disorders.
While
generally
regarded
as
safe,
with
adverse
effects
being
rare
and
typically
mild,
PPIs
have
been
associated
hypersensitivity
reactions.
These
reactions,
which
may
be
immediate
or
delayed,
vary
severity
from
mild
to
potentially
life-threatening.
This
review
provides
an
in-depth
analysis
of
key
aspects
PPI
use,
a
particular
emphasis
on
pathophysiological
characteristics
both
delayed
It
also
explores
cross-reactivity
offers
practical
framework
assist
clinicians
diagnosing
these
conditions
effectively.
Additionally,
highlights
critical
need
further
research
develop
standardized
diagnostic
therapeutic
protocols,
enabling
personalized
evidence-based
care
patients
experiencing
PPI-related
hypersensitivity.
Язык: Английский
Cathepsins and their role in gynecological cancers: Evidence from two-sample Mendelian randomization analysis
Medicine,
Год журнала:
2025,
Номер
104(10), С. e41653 - e41653
Опубликована: Март 7, 2025
Prior
studies
have
reported
connections
between
cathepsins
(CTS)
and
gynecological
cancers;
however,
the
exact
causal
links
are
yet
to
be
fully
understood.
Leveraging
publicly
accessible
genome-wide
association
study
summary
datasets,
we
performed
a
two-sample
bidirectional
Mendelian
randomization
(MR)
multivariate
MR
(MVMR)
analysis,
with
inverse
variance
weighted
(IVW)
method
as
primary
approach.
analysis
demonstrated
associations
CTSB
cervical
cancer
(IVW:
odds
ratio
[OR]
=
0.9995,
95%
confidence
interval
[CI]
0.9991-0.9999,
P
.0418),
CTSE
ovarian
OR
0.9197,
CI
0.8505-0.9944,
.0358),
CTSZ
0.9449,
0.8938-0.9990,
.0459),
high
grade
serous
0.8939,
0.8248-0.9689,
.0063),
0.9269,
0.8667-0.9913,
.0268).
A
positive
correlation
was
identified
CTSH
clear
cell
1.1496,
1.0368-1.2745,
.0081).
Nevertheless,
subsequent
adjustment
for
false
discovery
rate
revealed
that
none
of
P-values
retained
statistical
significance
(PFDR
>
0.05).
MVMR
results
elucidated
inversely
associated
0.9988,
0.9981-0.9996,
.0022).
Moreover,
noted
CTSF
1.0007,
1.0000-1.0014,
.0364),
similarly,
CTSS
1.0005,
1.0000-1.0011,
.0490).
CTSO
exhibited
non-endometrioid
endometrial
1.4405,
1.1864-1.7490,
<
.001),
positively
1.1167,
1.0131-1.2310,
.0263).
The
findings
reveal
emerges
protective
element
against
cancer,
whereas
represent
risk
factors
this
disease.
stands
out
factor
acts
cancer.
This
elucidates
causative
CTS
cancers,
providing
innovative
insights
diagnostic
therapeutic
optimization.
Язык: Английский