Use of proton pump inhibitors and risk of fragility hip fracture in a Mediterranean region

ObjectiveTo determine whether there is an increased risk of hip fracture associated with the use of proton pump inhibitors in a Mediterranean area after adjusting for other potential risk factors.MethodsRetrospective multicenter case–control study carried out in 6 primary health care centers in Catalonia, Spain. Cases were patients aged 50 years and over with a fragility hip fracture registered between January 2007 and December 2010, matched with 2 controls by sex and age. Data collected: use of proton pump inhibitors (type, dosage) in the 5 years previous to the hip fracture, socio-demographic data, body mass index, alcohol and tobacco consumption as well as health conditions and drugs associated with an increase risk of fragility hip fracture.Results358 cases were matched with 698 controls. The mean age was 82 years old in both groups. Women represented 77.1% in the case group and 76.9% in the control group. Crude association between proton pump inhibitors and hip fracture was 1.44 (95% CI, 1.09–1.89) and adjusted OR was 1.24 (95% CI, 0.93–1.65). No association was found with the continuous or discontinuous use of proton pump inhibitors, OR 1.17 (95% CI, 0.77–1.79), and OR of 1.16 (95% CI, 0.85–1.60) respectively. No association was found when restricting the analysis by sex, OR of 1.19 (95% CI, 0.27–5.14) or by age, younger or older than 80 years, OR of 0.72 (95% CI, 0.24–2.15).ConclusionThe use of proton pump inhibitors was not associated with an increased risk of hip fracture after adjusting for other risk factors in a Mediterranean area. This result suggests the existence of protective environmental factors linked to this southern area of Europe that eventually could compensate for the potential harm produced by proton pump inhibitors.     

The Addenbrooke’s Cognitive Examination-Revised accurately detects cognitive decline in Huntington’s disease

Cognitive features, which begin before manifestation of the motor features, are an integral part of Huntington’s disease and profoundly affect quality of life. A number of neuropsychological batteries have been used to assess this aspect of the condition, many of which are difficult to administer and time consuming, especially in advanced disease. We, therefore, investigated a simple and practical way to monitor cognition using the Addenbrooke’s Cognitive Examination-Revised (ACE-R) in 126 manifest Huntington’s disease patients, 28 premanifest gene carriers and 21 controls. Using this test, we demonstrated a selective decrease in phonemic, but not semantic, fluency in premanifest participants Cognitive decline in manifest Huntington’s disease varied according to disease severity with extensive cognitive decline observed in early-stage Huntington’s disease patients, indicating that this would be an optimal stage for interventions designed to halt cognitive decline, and lesser changes in the advanced cases. We next examined cognitive performance in patients prescribed antidopaminergic drugs as these drugs are known to decrease cognition when administered to healthy volunteers. We paradoxically found that these drugs may be beneficial, as early-stage Huntington’s disease participants in receipt of them had improved attention and Mini-Mental State Examination scores. In conclusion, this is the first study to test the usefulness of the ACE-R in a Huntington’s disease population and demonstrates that this is a brief, inexpensive and practical way to measure global cognitive performance in clinical practice with potential use in clinical trials.     

Music Therapy Assessment Tool for Awareness in Disorders of Consciousness (MATADOC): Standardisation of the principal subscale to assess awareness in patients with disorders of consciousness

Establishing valid and reliable measures for use with patients with disorders of consciousness (DOC) following profound brain injury is challenging due to a number of factors including the complex presentation of such patients and assessor variability. The auditory modality has been demonstrated to have greater sensitivity for detecting awareness in DOC patients. However, there are no measures developed to assess auditory responsiveness specifically. The objective of this study was to examine the psychometric properties of the principal subscale of a music therapy assessment tool (MATADOC) developed for use with adult DOC patients. The subscale assesses behavioural domains essential for diagnosis of awareness. Twenty-one adult patients were recruited from a specialist rehabilitation unit. In a prospective study with repeated measures, internal consistency, inter-rater and test–retest reliability and dimensionality were examined. The five-item scale showed satisfactory internal reliability (α = .76) and a strong first principal component. Corrected item-total correlations were all > .45. Inter-rater intra-class correlations (ICCs) ranged from 0.65–1.00 and intra-rater ICCs from 0.77–0.90. Rasch analysis confirmed these impressions of a reliable, unidimensional and homogenous scale. Diagnostic outcomes had 100% agreement with a validated external reference standard. The results indicate that the MATADOC principal subscale provides a new behavioural measure that can contribute to interdisciplinary assessment of awareness with DOC patients.     

Induction of atypical EAE mediated by transgenic production of IL‐6 in astrocytes in the absence of systemic IL‐6

Interleukin (IL)‐6 is crucial for the induction of many murine models of autoimmunity including experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. While IL‐6‐deficient mice (IL‐6 KO) are resistant to EAE, we showed previously that in transgenic mice with astrocyte‐targeted production of IL‐6‐restricted to the cerebellum (GFAP‐IL6), EAE induced with MOG_35–55 was redirected away from the spinal cord to the cerebellum. To further establish the importance of IL‐6 produced in the central nervous system, we have generated mice producing IL‐6 essentially only in the brain by crossing the GFAP‐IL6 mice with IL‐6 KO mice. Interestingly, GFAP‐IL6‐IL‐6 KO mice showed a milder but almost identical phenotype as the GFAP‐IL6 mice, which correlated with a lower load of inflammatory cells and decreased microglial reactivity. These results indicate that not only is cerebellar IL‐6 production and eventual leakage into the peripheral compartment the dominating factor controlling this type of EAE but that it can also facilitate induction of autoimmunity in the absence of normal systemic IL‐6 production. © 2013 Wiley Periodicals, Inc.     

POLR3A variants in hereditary spastic paraparesis and ataxia: clinical,genetic, and neuroradiological findings in a cohort of Italian patients

Neurological Sciences - Mutations in POLR3A are characterized by high phenotypic heterogeneity, with manifestations ranging from severe childhood-onset hypomyelinating leukodystrophic syndromes to...     

Cerebral amyloid load determination in a clinical setting: interpretation of amyloid biomarker discordances aided by tau and neurodegeneration measurements

Neurological Sciences - Alzheimer’s disease (AD) diagnosis can be hindered by amyloid biomarkers discordances. We aim to interpret discordances between amyloid positron emission tomography...     

The effect of low-intensity pulsed ultrasound on repair of epithelial cell monolayers in vitro

Low intensity pulsed ultrasound (LIPUS) is widely used to accelerate tissue regeneration following injury, but the biological mechanisms of this effect are poorly understood. An in vitro model of epithelial wound healing was used to investigate the effect of LIPUS on the reepithelialization of scrape wounds in normal human urothelial (NHU) cell monolayers. The effects of clinical doses of ultrasound treatment on NHU cell growth and migration were investigated in cells grown under optimal conditions, without growth supplements and in media containing low vs. physiological calcium concentrations. No differences in cell growth or migration were observed. We conclude that there is no direct effect upon uro-epithelial regeneration by therapeutic ultrasound in vitro and suggest that any stimulation of epithelial wound repair in vivo may occur indirectly, for example by modulating the extracellular matrix composition and/or production of paracrine factors by the stroma.