51,015 research outputs found
Relationship between antihypertensive medications and cognitive impairment: Part II. Review of Physiology and animal studies
Purpose of Review There is an established association between hypertension and increased risk of poor cognitive performance and dementia including Alzheimer’s disease; however, associations between antihypertensive medications (AHM) and dementia risk are less clear. An increased interest in AHM has resulted in expanding publications; however, none of the recent reviews provide comprehensive review. Our extensive review includes 24 mechanistic animal and human studies published over the last 5 years assessing relationship between AHM and cognitive function. Recent Findings All classes of AHM showed similar result patterns in animal studies. The mechanism by which AHM exert their effect was extensively studied by evaluating well-established pathways of AD disease process, including amyloid beta (Aβ), vascular, oxidative stress and inflammation pathways, but only few studies evaluated the blood pressure lowering effect on the AD disease process. Summary Methodological limitations of the studies prevent comprehensive conclusions prior to further work evaluating AHM in animals and larger human observational studies, and selecting those with promising results for future RCTs
Relationship between antihypertensive medications and cognitive impairment: Part I. review of human studies and clinical trials
Purpose of review: There is an established association between hypertension and increased risk of poor cognitive performance and dementia including Alzheimer’s disease; however, associations between antihypertensive medications (AHMs) and dementia risk are less consistent. An increased interest in AHM has resulted in expanding publications; however, none of the recent reviews are comprehensive. Our extensive review includes 15 observational and randomized controlled trials (RCTs) published over the last 5 years, assessing the relationship between AHM and cognitive impairment. Recent findings: All classes of AHM showed similar result patterns in human studies with the majority of study results reporting point estimates below one and only a small number of studies (N = 15) reporting statistically significant results in favor of a specific class. Summary: Only a small number of studies reported statistically significant results in favor of a specific class of AHM. Methodological limitations of the studies prevent definitive conclusions. Further work is now needed to evaluate the class of AHM and cognitive outcomes in future RCTs, with a particular focus on the drugs with the promising results in both animals and human observational studies
The clinical effectiveness and cost-effectiveness of inhaler devices used in the routine management of chronic asthma in older children: a systematic review and economic evaluation
Background:
This review examines the clinical effectiveness and
cost-effectiveness of hand-held inhalers to deliver
medication for the routine management of chronic
asthma in children aged between 5 and 15 years.
Asthma is a common disease of the airways, with a
prevalence of treated asthma in 5–15-year-olds of
around 12% and an actual prevalence in the community
as high as 23%. Treatment for the condition
is predominantly by inhalation of medication. There
are three main types of inhaler device, pressurised
metered dose, breath actuated, and dry powder, with
the option of the attachment of a spacer to the first
two devices under some prescribed circumstances.
Two recent reviews have examined the clinical and
cost-effectiveness evidence on inhaler devices, but
one was for children aged under 5 years and the
comparison in the second was made between pressurised
metered dose inhalers and other types only.
Objectives:
This review examines the clinical effectiveness and
cost-effectiveness of manual pressurised metered
dose inhalers, breath-actuated metered dose
inhalers, and breath-actuated dry powder inhalers,
with and without spacers as appropriate, to deliver
medication for the routine management of chronic
asthma in children aged between 5 and 15 years.
Methods:
Two previous HTA reviews have compared the
effectiveness of inhaler devices, one focusing on
asthma in children aged under 5 years and the
other on asthma and chronic obstructive airways
disease in all age groups. For the current review, a
literature search was carried out to identify all
evidence relating to the use of inhalers in older
children with chronic asthma. A search of in-vitro
studies undertaken for one of the previous reviews
was also updated.
The data sources used were: 15 electronic bibliographic
databases; the reference lists of one of the
previous HTA reports and other relevant articles;
health services research-related internet resources;
and all sponsor submissions.
Studies were selected according to strict inclusion
and exclusion criteria, and relevant information
concerning effectiveness and patient compliance
and preference was extracted directly on to an
extraction/evidence table. Quality assurance
was monitored.
Economic evaluation was undertaken by reviewing
existing cost-effective evidence. Further economic
modelling was carried out, and tables constructed
to determine device cost-minimisation and
incremental quality-adjusted life-year (QALY)
thresholds between devices.
Results:
Number and quality of studies, and
direction of evidence:
Fourteen randomised controlled studies were
identified relating to the clinical effectiveness of
inhaler devices for delivering β2-agonists. A further
five were on devices delivering corticosteroids and
one concerned the delivery of cromoglicate.
Overall, there were no differences in clinical
efficacy between inhaler devices, but a pressurised
metered dose inhaler with a spacer would appear
to be more effective than one without. These
findings endorse those of a previous HTA review
but extend them to other inhaler devices.
Seven randomised controlled trials examined the
impact on clinical effectiveness of using a nonchlorofluorocarbon
(CFC) propellant in place of
a CFC propellant in metered dose inhalers, both
pressurised and breath activated, although only one
study considered the latter type. No differences were
found between inhalers containing either propellant.
A further 30 studies of varying quality, from 12 randomised
controlled trials to non-controlled studies,
were identified that concerned the impact of use
by, and preference for, inhaler type, and treatment
adherence in children. Differences between the
studies, and limitations in comparative data between
various inhaler device types, make it difficult to draw
any firm conclusions from this evidence.
Summary of benefits:
No obvious benefits for one inhaler device type
over another for use in children aged 5–15 years
were identified.
Costs and cost per quality-adjusted
life-year:
Two approaches have been taken: cost-minimisation
and QALY threshold. In the QALY threshold
approach, additional QALYs that each device must
produce compared with a cheaper device to achieve
an acceptable cost per QALY were calculated. Using
the cheapest and most expensive devices for delivering
200 μg of beclometasone per day, assuming no
cost offset for any device, and a threshold of £5000,
the largest QALY needed was 0.00807. With such
a small QALY increase, no intervention can be
categorically rejected as not cost-effective.
Conclusions:
Generalisability of findings:
On the available evidence there are no obvious
benefits for one inhaler device over another
when used by children aged 5–15 years with
chronic asthma. However, the evidence, in the
majority of cases, was compiled on children
with mild to moderate asthma and restricted
to a limited number of drugs. Therefore the
findings may not be generalisable to those at
the more severe end of the spectrum of the
disease or to inhaler devices delivering some
of the drugs used in the management of asthma.
Need for further research:
Many of the previous studies are likely to
have been underpowered. Further clinical
trials with a robust methodology, sufficient
power and qualitative components are needed
to demonstrate any differences in clinical
resource use and patients’ asthma symptoms.
Further studies should also include the
behavioural aspects of patients towards their
medication and its delivery mechanisms.
It is acknowledged that sufficient power may
prove impractical owing to the large numbers
of patients required
Nonconventional screening of the Coulomb interaction in FexOy clusters: An ab-initio study
From microscopic point-dipole model calculations of the screening of the
Coulomb interaction in non-polar systems by polarizable atoms, it is known that
screening strongly depends on dimensionality. For example, in one dimensional
systems the short range interaction is screened, while the long range
interaction is anti-screened. This anti-screening is also observed in some zero
dimensional structures, i.e. molecular systems. By means of ab-initio
calculations in conjunction with the random-phase approximation (RPA) within
the FLAPW method we study screening of the Coulomb interaction in FexOy
clusters. For completeness these results are compared with their bulk
counterpart magnetite. It appears that the onsite Coulomb interaction is very
well screened both in the clusters and bulk. On the other hand for the
intersite Coulomb interaction the important observation is made that it is
almost contant throughout the clusters, while for the bulk it is almost
completely screened. More precisely and interestingly, in the clusters
anti-screening is observed by means of ab-initio calculations
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