AD is the most common form of dementia. The heritability is high, estimated to be between 60% and 80%1. This strong genetic component provides an opportunity to determine the pathophysiological processes in AD and to identify new biological features, new prognostic/diagnostic markers and new therapeutic targets through translational genomics. Characterizing the genetic risk factors in AD is therefore a major objective; with the advent of high-throughput genomic techniques, a large number of putative AD-associated loci/genes have been reported2. However, much of the underlying heritability remains unexplained. Hence, increasing the sample size of genome-wide association studies (GWASs) is an obvious solution that has already been used to characterize new genetic risk factors in other common, complex diseases (e.g., diabetes).
60 Selected Studies By Hanon Pdf 24
To quantify the effect size of the potential association between the GRS and conversion to dementia regarding predictive performance, we computed three different indices measuring different aspects of the predictive performance of the GRS in our prospective, longitudinal cohort studies91: the continuous version of the C-index,92,93 the continuous NRI94 and IPA95 (Supplementary Note). For all indices, we provide point estimates and 95% CIs.
In the main analysis, indices were computed at the time point for which all cohorts in a specific setting (i.e., population-based studies or memory clinics, respectively) provided follow-up observations (that is 5 years for population-based cohorts and 3 years for MCI cohorts). In a sensitivity analysis, indices for longer or shorter follow-up periods were also derived (that is 3 years and 10 years for population-based cohorts and 5 years for MCI cohorts). Standard errors for indices were derived by non-parametric bootstrapping with 1,000 samples.
The aim of this paper is to provide a narrative review covering the most important aspects of inhalation therapy devices, and to propose an evidence-based practical treatment algorithm for choosing an inhaler and for assessing proper inhaler use during patient follow-up, with a focus on adults. A multidisciplinary expert panel, including pulmonologists, general practitioners, nurses, and pharmacists, was set up to design a practical tool that allows a straightforward choice. Although the choice of molecule is equally important in the choice of inhalation therapy, this is out of the scope of this paper. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
Besides inhalation technique, another key factor in determining inhalation therapy success is patient adherence. As seen in other chronic diseases, adherence has been widely reported to be suboptimal in both asthma and COPD [12, 53]. As such, only one-third of asthma patients and half of COPD patients are considered to adhere to their medication [29, 53], but other studies suggest that, even in COPD patients, adherence can be as low as 36% [63]. As for inhalation technique, adherence is shown to be strongly associated with both clinical and economic outcomes, with evidence for increased exacerbations and hospitalizations, mortality, decreased quality of life, and loss of productivity in COPD patients [12, 17, 63, 69, 74]. The evaluation of patients with regard to adherence is therefore considered key [26, 27].
Several studies have shown that decreasing the complexity of inhalation therapy can improve disease control. As such, the use of separate inhalers was shown to result in higher direct and indirect medical costs compared to a single inhaler that combined treatments [6]. In addition, the use of several devices with mixed inhalation techniques resulted in significantly lower disease control and a higher rate of exacerbations as compared to when devices with a similar technique were used [9, 55]. The development and widespread use of pMDIs that can be used as both maintenance and reliever therapy in asthma further underscores the benefits of treating with a single inhaler type [26, 50].
Piano - Advanced; Early Advanced; Intermediate; Late IntermediateComplete. Composed by Charles-Louis Hanon. Edited by Allan Small. Masterworks; Piano Collection. Alfred Masterworks Editions. Studies and Classical. Piano studies book (comb-bound). With standard notation, fingerings and introductory text. 127 pages. Alfred Music #00-616C. Published by Alfred Music (AP.616C).
Hypertension results from a complex interaction of genes and environmental factors. Numerous common genetic variants with small effects on blood pressure have been identified[38] as well as some rare genetic variants with large effects on blood pressure.[39] Also, genome-wide association studies (GWAS) have identified 35 genetic loci related to blood pressure; 12 of these genetic loci influencing blood pressure were newly found.[40] Sentinel SNP for each new genetic locus identified has shown an association with DNA methylation at multiple nearby CpG sites. These sentinel SNP are located within genes related to vascular smooth muscle and renal function. DNA methylation might affect in some way linking common genetic variation to multiple phenotypes even though mechanisms underlying these associations are not understood. Single variant test performed in this study for the 35 sentinel SNP (known and new) showed that genetic variants singly or in aggregate contribute to risk of clinical phenotypes related to high blood pressure.[40]
Hypertension is very common in older people and a number of trials of antihypertensives have demonstrated benefit from treatment in even the oldest old. However, people with dementia were significantly under-represented in these studies and as a population are more likely to be physically frail, to suffer orthostatic hypotension and to experience adverse effects from polypharmacy at a lower drug count. It may be that different thresholds for commencement and cessation of treatment should be considered and may already be used for this group. Against this background this review sets out to describe the prevalence of hypertension in people with dementia, its treatment, change in treatment over time and the achievement of blood pressure (BP) control.
The PubMed, Cochrane, Embase and PsychINFO databases were searched for observational studies involving people with dementia and a diagnosis of hypertension. The search was limited to English language articles involving adults and humans published from 1990 onwards. Abstracts and titles were then reviewed with eligible articles read in full. Bibliographies were examined for further relevant studies. The final selection of studies was then analysed and appraised.
Thirteen articles were identified for analysis. The prevalence of hypertension in people with dementia was 45% (range 35%-84%). 73% of these were on at least one antihypertensive, with diuretics being the most common. The reported prevalence of hypertension in study populations remained unchanged over time. ACEi/ARBs and calcium channel blockers were prescribed more frequently in more recent studies whilst use of β-blockers and diuretics remained unchanged. Target blood pressure was achieved in 55% of those on treatment.
Having extracted the data from the selected articles, the combined data was analysed to test whether there has been any change in treatment patterns over time using regression analysis. Where needed data from the articles were transformed to facilitate comparison of data.
The characteristics of individual studies are summarised in Table 2. Of the 13 articles three reported studies which were conducted in the USA [15, 16], two each in the UK [17, 18] and France [19, 20] and one each in Brazil [21], Canada [22], Finland [23], Germany [24], Nigeria [25] and Norway [26].
All 13 studies were observational studies. 11 were cross-sectional and four of these were case-controlled [17, 18, 24, 26]. The remaining two were cohort studies [20, 27]. Of the 11 cross-sectional studies, six gathered data prospectively and five did so retrospectively [15, 17, 18, 24, 25]. Of the five retrospective studies the two UK studies and the German study used databases built using data held by primary care doctors [17, 18, 24], and the remaining two retrospectively analysed digital and hard copy hospital data [15, 25].
The objectives of the studies varied. Three set out to describe the clinical profile, including information on demographics, comorbidities and medications, of patients with dementia [21, 25, 27]. Four studies aimed to compare comorbidities and medication use between those with and without dementia [18, 23, 24, 26], while one aimed to look specifically at treatment in those with vascular cognitive impairment [22]. Two studies aimed to look at the association between antihypertensives and cognitive impairment [16, 17]. Two set out to evaluate the effect of antihypertensive therapy on cognitive function [19, 20] and one study aimed to compare blood pressure control and medication between different ethnic groups [15].
The prevalence of hypertension in people with dementia as reported by these studies varied between a minimum of 35% [27] and a maximum of 84% [24]. The mean prevalence of hypertension across the studies was 45% (SD 11%). There was no change in the prevalence of hypertension over time when earlier and more recent studies were compared.
Two studies reported details of the number of antihypertensives used [15, 20]. The mean number of antihypertensives was 2.4. Only one study reported on the achievement of target blood pressure [15], with 55% achieving this. This study involved 304 people, almost all male, in a Veteran Affairs hospital. 2ff7e9595c
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