Efficacy of Ginkgo biloba extract EGb 761(®) in dementia with behavioural and psychological symptoms: A systematic review.

To review current evidence of efficacy of Ginkgo biloba extract EGb 761(®) in dementia with behavioural and psychological symptoms (BPSD). Randomized, placebo-controlled trials assessing the effects of EGb 761(®) in dementia patients with BPSD were included if the diagnosis was made in accordance with internationally accepted criteria, the treatment period was at least 22 weeks, outcome measures covered BPSD and at least two of the following domains of assessment, i.e. cognition, activities of daily living and clinical global assessment, and methodological quality was adequate. An analysis of covariance (ANCOVA) model was used to calculate the pooled effect estimates and to compare effects of EGb 761(®) and placebo; furthermore, combined risk differences of response rates were calculated. Four published trials were identified, involving altogether 1,628 outpatients with mild to moderate dementia. Least-square mean differences for change from baseline in cognition, BPSD (including caregiver distress rating), activities of daily living, clinical global impression, and quality of life favoured EGb 761(®) (P < 0.001 for all comparisons). The pooled analyses provide evidence of efficacy of EGb 761(®) at a daily dose of 240 mg in the treatment of out-patients suffering from Alzheimer's, vascular or mixed dementia with BPSD

Interventional psychiatry in the management of behavioural and psychological symptoms of dementia: a qualitative review.

“Behavioural and psychological symptoms of dementia” (BPSD) refers to a heterogeneous group of clinical manifestations related to dementia, including apathy, depression, anxiety, delusions, hallucinations, sexual or social disinhibition, sleep-wake cycle disturbances, aggression, agitation and other behaviours considered inappropriate. Because of the complexity and heterogeneity of BPSD, as well as the fragility and multimorbidity of the elderly, pharmacological treatment appears to be limited in terms of safety and efficacy, and nonpharmacological therapies are today considered the first choice. There is growing evidence that interventional approaches such as electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS) could be safe and efficient options for several psychiatric illnesses in a population presenting resistance to and/or intolerance of pharmacotherapy. The aim of the present work is to provide a qualitative review of the state of the art in interventional psychiatry in the treatment of BPSD. A particular focus will be on depression and agitation, which represent major stressors on caregivers and a primary cause of institutionalisation. ECT is probably the most promising interventional procedure needing further investigation in order to obtain specific protocols and a consensus on indications. Preliminary data on rTMS, tDCS, and VNS are encouraging although randomised controlled trials to investigate and compare their efficacy in the treatment of BPSD are still lacking. Their feasibility profile could represent an important advantage over ECT. DBS could represent a very effective therapy for behavioural disorders, but knowledge of the precise neuroanatomical targets for BPSD is currently too limited to justify this invasive approach

Brain Aging in the Oldest-Old

Nonagenarians and centenarians represent a quickly growing age group worldwide. In parallel, the prevalence of dementia increases substantially, but how to define dementia in this oldest-old age segment remains unclear. Although the idea that the risk of Alzheimer's disease (AD) decreases after age 90 has now been questioned, the oldest-old still represent a population relatively resistant to degenerative brain processes. Brain aging is characterised by the formation of neurofibrillary tangles (NFTs) and senile plaques (SPs) as well as neuronal and synaptic loss in both cognitively intact individuals and patients with AD. In nondemented cases NFTs are usually restricted to the hippocampal formation, whereas the progressive involvement of the association areas in the temporal neocortex parallels the development of overt clinical signs of dementia. In contrast, there is little correlation between the quantitative distribution of SP and AD severity. The pattern of lesion distribution and neuronal loss changes in extreme aging relative to the younger-old. In contrast to younger cases where dementia is mainly related to severe NFT formation within adjacent components of the medial and inferior aspects of the temporal cortex, oldest-old individuals display a preferential involvement of the anterior part of the CA1 field of the hippocampus whereas the inferior temporal and frontal association areas are relatively spared. This pattern suggests that both the extent of NFT development in the hippocampus as well as a displacement of subregional NFT distribution within the Cornu ammonis (CA) fields may be key determinants of dementia in the very old. Cortical association areas are relatively preserved. The progression of NFT formation across increasing cognitive impairment was significantly slower in nonagenarians and centenarians compared to younger cases in the CA1 field and entorhinal cortex. The total amount of amyloid and the neuronal loss in these regions were also significantly lower than those reported in younger AD cases. Overall, there is evidence that pathological substrates of cognitive deterioration in the oldest-old are different from those observed in the younger-old. Microvascular parameters such as mean capillary diameters may be key factors to consider for the prediction of cognitive decline in the oldest-old. Neuropathological particularities of the oldest-old may be related to “longevity-enabling” genes although little or nothing is known in this promising field of future research

Epidemiology of at-risk alcohol use and associated comorbidities of interest among community-dwelling older adults: a protocol for a systematic review.

There is little epidemiological evidence and knowledge about at-risk alcohol use among community-dwelling older adults and their chronic and acute alcohol-related comorbidities of interest. This systematic review will summarise and examine relevant studies about the epidemiology of at-risk alcohol use and associated comorbidities of interest in this population. We will search the following databases, without language or date restrictions, from inception to 31 August 2019: Embase.com, Medline Ovid SP, Pubmed (NOT medline[sb]), CINAHL EBSCO, PsycINFO Ovid SP, Central-Cochrane Library Wiley and Web of Science (Core Collection). Search strategies will be developed in collaboration with a librarian. We will use predefined search terms for alcoholism, epidemiology, the elderly, living place and comorbidities of interest, as well as terms related to the identification of "measurements", "tools" or "instruments" for measuring harm from alcohol use. At-risk status will be determined by the amount of alcohol consumed and any comorbidities of interest associated with at-risk alcohol use, with the latter being documented separately or using an assessment tool for at-risk drinking. We will also examine the bibliographies of all the relevant articles found and search for unpublished studies. We will consider publications in all languages. No ethical approval is necessary. Results will be presented in national and international conferences on addiction and published in a peer-reviewed journal. CRD42018099965

Impact of an interdisciplinary strategy on antibiotic use: a prospective controlled study in three hospitals

Objectives: Evaluation of the impact of the implementation of practice guidelines, with or without their reinforcement by a pharmacist, on the intra-hospital use of antibiotics. Materials and methods: The duration of antibiotic treatment, their cost, and the length of patient stay were compared in three secondary-care hospitals, before and after interventions that were designed to promote rational antibiotic use. After randomization, hospital A received no intervention (control), local practice guidelines were implemented in hospital B (low grade intervention), and these guidelines were reinforced by a clinical pharmacist in hospital C (high grade intervention). Adherence to the guidelines was measured in hospitals B and C. Multivariable statistical analyses were carried out to adjust for confounding factors. Results: None of the outcomes measured in the 1200 included patients decreased between the two study periods in any hospital. Hospital A was significantly and independently associated with an increase in the duration of antibiotic treatments, the cost of antibiotics (acquisition and global costs), and the length of stay. Although these differences were not statistically significant, increases in hospital B were higher than in hospital C. Adherence to guidelines was significantly higher in hospital C. Conclusions: Even though interdisciplinary interventions aiming at rationalizing antibiotic use could not diminish the duration of treatments, their costs or the length of stay, they proved useful to control the progression of these parameter

Brain Aging in the Oldest-Old

Nonagenarians and centenarians represent a quickly growing age group worldwide. In parallel, the prevalence of dementia increases substantially, but how to define dementia in this oldest-old age segment remains unclear. Although the idea that the risk of Alzheimer's disease (AD) decreases after age 90 has now been questioned, the oldest-old still represent a population relatively resistant to degenerative brain processes. Brain aging is characterised by the formation of neurofibrillary tangles (NFTs) and senile plaques (SPs) as well as neuronal and synaptic loss in both cognitively intact individuals and patients with AD. In nondemented cases NFTs are usually restricted to the hippocampal formation, whereas the progressive involvement of the association areas in the temporal neocortex parallels the development of overt clinical signs of dementia. In contrast, there is little correlation between the quantitative distribution of SP and AD severity. The pattern of lesion distribution and neuronal loss changes in extreme aging relative to the younger-old. In contrast to younger cases where dementia is mainly related to severe NFT formation within adjacent components of the medial and inferior aspects of the temporal cortex, oldest-old individuals display a preferential involvement of the anterior part of the CA1 field of the hippocampus whereas the inferior temporal and frontal association areas are relatively spared. This pattern suggests that both the extent of NFT development in the hippocampus as well as a displacement of subregional NFT distribution within the Cornu ammonis (CA) fields may be key determinants of dementia in the very old. Cortical association areas are relatively preserved. The progression of NFT formation across increasing cognitive impairment was significantly slower in nonagenarians and centenarians compared to younger cases in the CA1 field and entorhinal cortex. The total amount of amyloid and the neuronal loss in these regions were also significantly lower than those reported in younger AD cases. Overall, there is evidence that pathological substrates of cognitive deterioration in the oldest-old are different from those observed in the youngerold. Microvascular parameters such as mean capillary diameters may be key factors to consider for the prediction of cognitive decline in the oldest-old. Neuropathological particularities of the oldest-old may be related to "longevity-enabling" genes although little or nothing is known in this promising field of future research

Impact of an interdisciplinary strategy on antibiotic use: a prospective controlled study in three hospitals.

OBJECTIVES: Evaluation of the impact of the implementation of practice guidelines, with or without their reinforcement by a pharmacist, on the intra-hospital use of antibiotics. MATERIALS AND METHODS: The duration of antibiotic treatment, their cost, and the length of patient stay were compared in three secondary-care hospitals, before and after interventions that were designed to promote rational antibiotic use. After randomization, hospital A received no intervention (control), local practice guidelines were implemented in hospital B (low grade intervention), and these guidelines were reinforced by a clinical pharmacist in hospital C (high grade intervention). Adherence to the guidelines was measured in hospitals B and C. Multivariable statistical analyses were carried out to adjust for confounding factors. RESULTS: None of the outcomes measured in the 1200 included patients decreased between the two study periods in any hospital. Hospital A was significantly and independently associated with an increase in the duration of antibiotic treatments, the cost of antibiotics (acquisition and global costs), and the length of stay. Although these differences were not statistically significant, increases in hospital B were higher than in hospital C. Adherence to guidelines was significantly higher in hospital C. CONCLUSIONS: Even though interdisciplinary interventions aiming at rationalizing antibiotic use could not diminish the duration of treatments, their costs or the length of stay, they proved useful to control the progression of these parameters

Modulation of Neutrophil Function by Recombinant Human IgG1 Fc Hexamer in the Endogenous K/BxN Mouse Model of Rheumatoid Arthritis.

INTRODUCTION Neutrophils are a pivotal cell type in the K/BxN mouse model of rheumatoid arthritis and play an essential role in the progression of the arthritis. They are readily activated by immune complexes (ICs) via their FcγRs to release IL-1β in addition to other cytokines, which are inducing cartilage destruction. Neutrophils also release neutrophil-active chemokines to recruit themselves in an autocrine manner to perpetuate tissue destruction. FcγR-expression on neutrophils is of crucial importance for the recognition of ICs. METHODS In this study, due to its high avidity for binding to FcγRs, we investigated the potential anti-inflammatory effect of a recombinant IgG1 Fc hexamer (rFc-µTP-L309C) on neutrophils in the K/BxN mouse model of endogenously generated chronic arthritis. 200 mg/kg rFc-µTP-L309C and human serum albumin (HSA), used as controls, were administered subcutaneously every other day. Mouse ankle joints were monitored daily to generate a clinical score. Immunohistology was used to evaluate neutrophil infiltration and TUNEL to assess apoptosis. ELISA was used to measure IL-1β. RESULTS Treatment with rFc-µTP-L309C, but not HSA, was able to significantly ameliorate the arthritis in the K/BxN mice. Significant neutrophil infiltration into the ankle joint was found, but treatment with rFc-µTP-L309C resulted in significantly less neutrophil infiltration. There was no significant influence of rFc-µTP-L309C on neutrophil death or apoptosis. Less neutrophil infiltration could not be correlated to chemokine-mediated migration. Significantly less IL-1β was measured in mice treated with rFc-µTP-L309C. CONCLUSION In the endogenous K/BxN mouse model of rheumatoid arthritis, amelioration can be explained in part by inhibition of neutrophil infiltration into the joints as well as inhibition of IL-1β production. Given the observed inhibitory properties on neutrophils, rFc-µTP-L309C may be a potential therapeutic candidate to treat autoimmune and inflammatory conditions in which neutrophils are the predominant cell type involved in pathogenesis

Demographics, Clinical Characteristics, and Therapeutic Approaches among Older Adults Referred to Mobile Psychiatric Crisis Intervention Teams: A Retrospective Study.

The advent of mobile old age psychiatry intervention teams supports policies maintaining older adults in their habitual living environments, even those who are very old and suffering from acute cognitive and psychiatric impairments. Analyzing sociodemographic data, clinical and health characteristics, reasons for crisis-oriented psychiatric consultations, and other therapeutic suggestions for supporting home- or nursing home-dwelling older adult patients suffering from an onset of a psychiatric crisis. Reviews of the medical records and discharge letters of home- or nursing home-dwelling older adults who had undergone a consultation with the Lausanne region's Mobile Old Age Psychiatry Teams (MOAPTs), between May 2016 and December 2017. Of 570 older adult patients referred for consultation with MOAPTs, 333 had medical records and discharge letters eligible for retrospective analysis (59%). The majority of these older adult patients were women aged over 80 years suffering from dementia, mood disorders with and without a risk of suicide, and delirium. Challenging behaviors related to different stages of cognitive impairment were the most important clinical reason for crisis consultations. Nonpharmacological and pharmacological treatments were delivered concurrently in 68% of crisis consultations. Appropriate responses by dual nurse-psychiatrist teams using crisis-oriented nonpharmacological and pharmacological interventions decreased hospitalization

Clinical Use and Therapeutic Potential of IVIG/SCIG, Plasma-Derived IgA or IgM, and Other Alternative Immunoglobulin Preparations

Intravenous and subcutaneous immunoglobulin preparations, consisting of IgG class antibodies, are increasingly used to treat a broad range of pathological conditions, including humoral immune deficiencies, as well as acute and chronic inflammatory or autoimmune disorders. A plethora of Fab- or Fc-mediated immune regulatory mechanisms has been described that might act separately or in concert, depending on pathogenesis or stage of clinical condition. Attempts have been undertaken to improve the efficacy of polyclonal IgG preparations, including the identification of relevant subfractions, mild chemical modification of molecules, or modification of carbohydrate side chains. Furthermore, plasma-derived IgA or IgM preparations may exhibit characteristics that might be exploited therapeutically. The need for improved treatment strategies without increase in plasma demand is a goal and might be achieved by more optimal use of plasma-derived proteins, including the IgA and the IgM fractions. This article provides an overview on the current knowledge and future strategies to improve the efficacy of regular IgG preparations and discusses the potential of human plasma-derived IgA, IgM, and preparations composed of mixtures of IgG, IgA, and IgM