Falls are a major public health problem in older adults. Earlier studies showed that psychotropic medication use increases the risk of falls. The aim of this study is to update the current knowledge ...by providing a comprehensive systematic review and meta-analysis on psychotropic medication use and falls in older adults.
This study is a systematic review and meta-analysis. A search was conducted in Medline, PsycINFO, and Embase. Key search concepts were "falls," "aged," "medication," and "causality." Studies were included that investigated psychotropics (antipsychotics, antidepressants, anxiolytics, sedatives, and hypnotics) as risk factors for falls in participants ≥60 years of age or participants with a mean age of ≥70 years. Meta-analyses were performed using generic inverse variance method pooling unadjusted and adjusted odds ratio (OR) estimates separately.
In total, 248 studies met the inclusion criteria for qualitative synthesis. Meta-analyses using adjusted data showed the following pooled ORs: antipsychotics 1.54 95% confidence interval (CI) 1.28-1.85, antidepressants 1.57 (95% Cl 1.43-1.74), tricyclic antidepressants 1.41 (95% CI 1.07-1.86), selective serotonin reuptake inhibitors 2.02 (95% CI 1.85-2.20), benzodiazepines 1.42 (95%, CI 1.22-1.65), long-acting benzodiazepines 1.81 (95%, CI 1.05-3.16), and short-acting benzodiazepines 1.27 (95%, CI 1.04-1.56) Most of the meta-analyses resulted in substantial heterogeneity that did not disappear after stratification for population and healthcare setting.
Antipsychotics, antidepressants, and benzodiazepines are consistently associated with a higher risk of falls. It is unclear whether specific subgroups such as short-acting benzodiazepines and selective serotonin reuptake inhibitors are safer in terms of fall risk. Prescription bias could not be accounted for. Future studies need to address pharmacologic subgroups as fall risk may differ depending on specific medication properties. Precise and uniform classification of target medication (Anatomical Therapeutic Chemical Classification) is essential for valid comparisons between studies.
The significance of amyloid precursor protein (APP) and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD) is unknown.
To investigate the role of ...soluble APP (sAPP) and amyloid beta (Aβ) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to brain biopsy Aβ and hyperphosphorylated tau (HPτ) findings.
The study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Aβ and HPτ. CSF levels of AD-related biomarkers (Aβ42, p-tau, total tau), non-AD-related Aβ isoforms (Aβ38, Aβ40), sAPP isoforms (sAPPα, sAPPβ), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE.
Lumbar CSF levels of sAPPα were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPβ showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Aβ or HPτ in the brain biopsy. Quantified Aβ load in the brain biopsy showed a negative correlation with CSF levels of Aβ42 in ventricular (r = -0.295, p = 0.003) and lumbar (r = -0.356, p = 0.01) samples, while the levels of Aβ38 and Aβ40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the brain biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure.
The role of sAPP isoforms in iNPH seems to be independent from the amyloid cascade. No neuroinflammatory background was observed in iNPH or AD.
Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently increased understanding of the ...effectiveness of colonoscopic surveillance and the heterogeneity of cancer risk between genotypes. The need for gene- and gender-specific guidelines has been acknowledged.
The European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP) developed a multidisciplinary working group consisting of surgeons, clinical and molecular geneticists, pathologists, epidemiologists, gastroenterologists, and patient representation to conduct a graded evidence review. The previous Mallorca guideline format was used to revise the clinical guidance. Consensus for the guidance statements was acquired by three Delphi voting rounds.
Recommendations for clinical and molecular identification of Lynch syndrome, surgical and endoscopic management of Lynch syndrome-associated colorectal cancer, and preventive measures for cancer were produced. The emphasis was on surgical and gastroenterological aspects of the cancer spectrum. Manchester consensus guidelines for gynaecological management were endorsed. Executive and layperson summaries were provided.
The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented.
To assess the relationship between Alzheimer disease (AD)-related pathologic changes in frontal cortical brain biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships ...of AD biomarkers in CSF and cortical biopsy with the final clinical diagnosis of AD.
In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), Aβ plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF Aβ42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia.
The patients with Aβ plaques in the cortical biopsy had lower (p = 0.009) CSF Aβ42 levels than those with no Aβ plaques. The patients with tau in the cortical biopsy had lower (p = 0.014) Aβ42 but higher (p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical biopsy. The patients with amyloid + tau + biopsies had the lowest Aβ42 and highest tau and p-tau 181 levels in CSF. The Aβ42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical Aβ was independently predicted by the APOE ε4 carrier status and age but not by CSF Aβ42 or tau levels.
Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF Aβ42 and high CSF tau and p-tau levels, respectively.
Energetic electron precipitation (EEP) from the Earth's outer radiation belt continuously affects the chemical composition of the polar mesosphere. EEP can contribute to catalytic ozone loss in the ...mesosphere through ionization and enhanced production of odd hydrogen. However, the long-term mesospheric ozone variability caused by EEP has not been quantified or confirmed to date. Here we show, using observations from three different satellite instruments, that EEP events strongly affect ozone at 60-80 km, leading to extremely large (up to 90%) short-term ozone depletion. This impact is comparable to that of large, but much less frequent, solar proton events. On solar cycle timescales, we find that EEP causes ozone variations of up to 34% at 70-80 km. With such a magnitude, it is reasonable to suspect that EEP could be an important part of solar influence on the atmosphere and climate system.
The objective of this paper was to compare health outcomes and hospital care use of very low birth weight (VLBW), and very preterm (VLGA) infants in seven European countries. Analysis was performed ...on linkable patient-level registry data from seven European countries between 2006 and 2008 (Finland, Hungary, Italy (the Province of Rome), the Netherlands, Norway, Scotland, and Sweden). Mortality and length of stay (LoS) were adjusted for differences in gestational age (GA), sex, intrauterine growth, Apgar score at five minutes, parity and multiple births. The analysis included 16,087 infants. Both the 30-day and one-year adjusted mortality rates were lowest in the Nordic countries (Finland, Sweden and Norway) and Scotland and highest in Hungary and the Netherlands. For survivors, the adjusted average LoS during the first year of life ranged from 56 days in the Netherlands and Scotland to 81 days in Hungary. There were large differences between European countries in mortality rates and LoS in VLBW and VLGA infants. Substantial data linkage problems were observed in most countries due to inadequate identification procedures at birth, which limit data validity and should be addressed by policy makers across Europe.
The objective of the study was to examine the role of microsatellite instability (MSI) and BRAF(V600E)mutation in colorectal cancer (CRC) by categorising patients into more detailed subtypes based on ...tumour characteristics.
Tumour samples from 762 population-based patients with sporadic CRC were analysed for MSI and BRAF(V600E) by immunohistochemistry. Patient survival was followed-up for a median of 5.2 years.
Compared with microsatellite stable (MSS) CRC, MSI was prognostic for better disease-free survival (DFS; 5 years: 85.8% vs 75.3%, 10 years: 85.8% vs 72.9%, P=0.027; HR 0.49, CI 0.30-0.80, P=0.005) and disease-specific survival (DSS; 5 years: 83.2% vs 70.5%; 10 years: 83.2 vs 65.0%, P=0.004). Compared with BRAF wild type, BRAF(V600E) was a risk for poor survival (overall survival; 5 years: 62.3% vs 51.6%, P=0.014; HR 1.43, CI 1.07-1.90, P=0.009), especially in rectal cancer (for DSS, HR: 10.60, CI: 3.04-36.92, P<0.001). The MSS/BRAF(V600E) subtype was a risk for poor DSS (HR: 1.88, CI: 1.06-3.31, P=0.030), but MSI/BRAF(V600E) was a prognostic factor for DFS (HR: 0.42, CI: 0.18-0.96, P=0.039). Among stage I-II patients, the MSS/BRAF(V600E) subtype was independently associated with poor DSS (HR: 5.32, CI: 1.74-16.31, P=0.003).
Microsatellite instable tumours were associated with better prognosis compared with MSS. BRAF(V600E) was associated with poor prognosis unless it occurred together with MSI. The MSI/BRAF(V600E) subtype was a favourable prognostic factor compared with the MSS/BRAF wild-type subtype. BRAF(V600E) rectal tumours showed particularly poor prognosis. The MSS/BRAF(V600E) subtype was associated with increased disease-specific mortality even in stage I-II CRC.
The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis ...using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse breeds using a newly developed high-density genotyping array consisting of >170,000 evenly spaced SNPs. We first identify 44 genomic regions exhibiting extreme differentiation across multiple breeds. Genetic variation in these regions correlates with variation in several phenotypic traits that vary between breeds, and we identify novel associations with both morphological and behavioral traits. We next scan the genome for signatures of selective sweeps in single breeds, characterized by long regions of reduced heterozygosity and fixation of extended haplotypes. These scans identify hundreds of regions, including 22 blocks of homozygosity longer than one megabase in certain breeds. Candidate selection loci are strongly enriched for developmental genes. We chose one highly differentiated region, associated with body size and ear morphology, and characterized it using high-throughput sequencing to provide a list of variants that may directly affect these traits. This study provides a catalogue of genomic regions showing extreme reduction in genetic variation or population differentiation in dogs, including many linked to phenotypic variation. The many blocks of reduced haplotype diversity observed across the genome in dog breeds are the result of both selection and genetic drift, but extended blocks of homozygosity on a megabase scale appear to be best explained by selection. Further elucidation of the variants under selection will help to uncover the genetic basis of complex traits and disease.
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