A systematic review and meta-analysis comparing carer focused and dyadic multicomponent interventions for cares of people with dementia

CC BY-NCObjective: The aim of this study was to compare the efficacy of two approaches: multicomponent interventions that focus on working with the carer and dyadic interventions that work with both the carer and the person with dementia. Method: A systematic review involving a search of Medline, EMBASE, and PsycINFO in October 2015 was performed. Randomized controlled trials involving carers of people with dementia and comparing multicomponent interventions with usual care were included. Results: Pooling of all studies demonstrated that multicomponent interventions can reduce depressive symptoms, improve quality of life, reduce carer impact, and reduce behavioral and psychological symptoms of dementia as well as caregiver upset with these symptoms. We were unable to find a significant difference in the effects of dyadic interventions in comparison with carer focused interventions for these outcomes. Discussion: Although effect sizes associated with intervention are small, multicomponent interventions are relatively inexpensive to deliver, acceptable, and widely applicable

Linking the evidence: intermediate outcomes in medical test assessments

Objectives To review how health technology assessments (HTA) of medical tests incorporate intermediate outcomes in conclusions about the effectiveness of tests on improving health outcomes. Methods Systematic review of English-language test assessments in the HTA database from January 2005 to February 2010, supplemented by a search of the websites of International Network of Agencies for Health Technology Assessment (INAHTA) members. Results 149 HTAs from eight countries were assessed. Half evaluated tests for screening or diagnosis, a third for disease classification (including staging, prognosis, monitoring), and a fifth for multiple purposes. In 71 HTAs (48%) only diagnostic accuracy was reported, while in 17 (11%) evidence of health outcomes was reported in addition to accuracy. Intermediate outcomes, mainly the impact of test results on patient management, were considered in 61 HTAs (41%). Of these, 47 identified randomized trials or observational studies reporting intermediate outcomes. The validity of these intermediate outcomes as a surrogate for health outcomes was not consistently discussed; nor was the quality appraisal of this evidence. Clear conclusions about whether the test was effective were included in about 60% of HTAs. Conclusions Intermediate outcomes are frequently assessed in medical test HTAs, but interpretation of this evidence is inconsistently reported. We recommend that reviewers explain the rationale for using intermediate outcomes, identify the assumptions required to link intermediate outcomes and patient benefits and harms, and assess the quality of included studies

Interventions to delay functional decline in people with dementia: a systematic review of systematic reviews.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Objective To summarise existing systematic reviews that assess the effects of non-pharmacological, pharmacological and alternative therapies on activities of daily living (ADL) function in people with dementia. Design Overview of systematic reviews. Methods A systematic search in the Cochrane Database of Systematic Reviews, DARE, Medline, EMBASE and PsycInfo in April 2015. Systematic reviews of randomised controlled trials conducted in people with Alzheimer's disease or dementia measuring the impact on ADL function were included. Methodological quality of the systematic reviews was independently assessed by two authors using the AMSTAR tool. The quality of evidence of the primary studies for each intervention was assessed using GRADE. Results A total of 23 systematic reviews were included in the overview. The quality of the reviews varied; however most (65%) scored 8/11 or more on the AMSTAR tool, indicating high quality. Interventions that were reported to be effective in minimising decline in ADL function were: exercise (6 studies, 289 participants, standardised mean difference (SMD) 0.68, 95% CI 0.08 to 1.27; GRADE: low), dyadic interventions (8 studies, 988 participants, SMD 0.37, 95% CI 0.05 to 0.69; GRADE: low) acetylcholinesterase inhibitors and memantine (12 studies, 4661 participants, donepezil 10 mg SMD 0.18, 95% CI 0.03 to 0.32; GRADE: moderate), selegiline (7 studies, 810 participants, SMD 0.27, 95% CI 0.13 to 0.41; GRADE: low), huperzine A (2 studies, 70 participants, SMD 1.48, 95% CI 0.95 to 2.02; GRADE: very low) and Ginkgo biloba (7 studies, 2530 participants, SMD 0.36, 95% CI 0.28 to 0.44; GRADE: very low). Conclusions Healthcare professionals should ensure that people with dementia are encouraged to exercise and that primary carers are trained and supported to provide safe and effective care for the person with dementia. Acetylcholinesterase inhibitors or memantine should be trialled unless contraindicated. Trial registration number CRD42015020179

Oxidized Amino Acids in Lens Protein with Age: Measurement of o-Tyrosine and Dityrosine in the Aging Human Lens

The concentrations of ortho-tyrosine (o-Tyr) and dityrosine (DT) were measured in noncataractous human lenses in order to assess the role of proteinoxidation reactions in the aging of lens proteins. The measurements were conducted by selected ion monitoring-gas chromatography/mass spectrometry using deuterium-labeled internal standards, which provided both high sensitivity and specificity for the quantitation of o-Tyr and DT. Between ages 1 and 78 years, the o-Tyr concentration in lens proteins varied from 0.3 to 0.9 mmol of o-Tyr/mol of Phe (n = 19), while DT ranged from 1 to 3 mumol of DT/mol of Tyr (n = 30). There were no significant changes in levels of o-Tyr with lens age. There was a statistically significant, but only slight, increase in DT in lens proteins with age (approximately 33% increases between ages 1 and 78, r = 0.5, p \u3c 0.01). At the same time, totalprotein fluorescence, measured at DT wavelengths (Ex = 317 nm, Em = 407 nm), increased 11-fold between ages 1 and 78 and correlated strongly with age (r = 0.82, p \u3c 0.0001). Although the fluorescence maxima of lens proteins were similar to those of DT, DT accounted for less than 1% of the DT-like fluorescence in lens protein at all ages. These observations indicate that oxidation of Phe and Tyr plays a limited role in the normal aging of lens proteins in vivo

Effect of Phosphate on the Kinetics and Specificity of Glycation of Protein

The glycation (nonenzymatic glycosylation) of several proteins was studied in various buffiner os rder to assess the effects of buffering ions on the kinetics and specificity of glycation of protein. Incubation of RNase with glucose in phosphate buffer resulted in inactivation of the enzyme because of preferential modification of lysine residues ino r near the activsei te. In contrast, in the cationic buffers, 3-(N-morpholino)propanesulfonic acid and 3-(N-tris(hydroxymethyl)rnethylamino)- 2-hydroxypropanesulfonica cid, the kineticso f glycation of RNase were decreased 2- to 3-fold, there was a decrease in glycation of active site versus peripheral lysines, and the enzyme was resistant to inactivation by glucose. The extent of Schiff base formation on RNase was comparable in the three buffers, suggesting that phosphate, bound in the active site of RNase, catalyzed the Amadori rearrangement at active site lysines, leading to the enhanced rate of inactivation of the enzyme. Phosphate catalysis of glycation was concentration-dependent and could be mimicked by arsenate. Phosphate also stimulated the rate of glycation of other proteins, such as lysozyme, cytochrome c, albumin, and hemoglobin. As with RNase, phosphate affected the specificity of glycation of hemoglobin, resulting in increasegdly cation of amino-terminal valine versus intrachain lysine residues. 2,3-Diphosphoglycerate exerted similar effeocnt st he glycation of hemoglobin, suggesting that inorganic and organic phosphates may play an important role in determining the kinetics and specificity of glycation of hemoglobin in the red cell. Overall, these studies establishth at buffering ions or ligands can exert significant effects on the kinetics ands pecificity of glycation of proteins

The diagnostic accuracy of the Kimberley Indigenous Cognitive Assessment (KICA) tool: a systematic review

Copyright © 2017 The Royal Australian and New Zealand College of Psychiatrists. Reprinted by permission of SAGE PublicationsObjectives: The objective of this study was to conduct a systematic review of evidence for the accuracy of the Kimberley Indigenous Cognitive Assessment (KICA) tool in supporting the diagnosis of dementia in Indigenous Australian populations. Methods: Cross-sectional diagnostic accuracy studies of the KICA with an appropriate reference standard published to November 2015 were included. Comparison to an alternative cognitive assessment tool was required in non-remote populations. Case control analyses were excluded. Results: Four studies were included: one of the KICA-Cog and KICA-Carer, one of the KICA Screen, and two of the modified-KICA. All tools developed for remote populations had a sensitivity of ≥76% and a specificity of ≥71% for the diagnosis of dementia. The KICA-Cog and KICA-Carer conducted in series had the highest sensitivity and specificity (91% and 94% respectively). In an urban and regional population, the mKICA had similar accuracy to the Mini-Mental State Examination (MMSE) (AUC 0.93, 95% CI 0.88–0.99 vs 0.94, 95% CI 0.89–0.99). Key risk of bias limitations related to lack of pre-determined cut-points and population selection methods. Conclusion: The use of the KICA in remote Indigenous Australians may assist in timely diagnosis of dementia in this population. Using the KICA-Cog and KICA-Carer in series may maximise specificity, decreasing false positive results without compromising sensitivity

A critical review of the long-term disability outcomes following hip fracture

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Hip fractures are an increasingly common consequence of falls in older people that are associated with a high risk of death and reduced function. This review aims to quantify the impact of hip fracture on older people’s abilities and quality of life over the long term. Methods: Studies were identified through PubMed and Scopus searches and contact with experts. Cohort studies of hip fracture patients reporting outcomes 3 months post-fracture or longer were included for review. Outcomes of mobility, participation in domestic and community activities, health, accommodation or quality of life were categorised according to the World Health Organization’s International Classification of Functioning and synthesised narratively. Risk of bias was assessed according to four items from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Results: Thirty-eight studies from 42 publications were included for review. Most followed a clearly defined sample from the time of fracture. Hip fracture survivors experienced significantly worse mobility, independence in function, health, quality of life and higher rates of institutionalisation than age matched controls. The bulk of recovery of walking ability and activities for daily living occurred within 6 months after fracture. Between 40 and 60 % of study participants recovered their pre-fracture level of mobility and ability to perform instrumental activities of daily living, while 40–70 % regained their level of independence for basic activities of daily living. For people independent in self-care pre-fracture, 20–60 % required assistance for various tasks 1 and 2 years after fracture. Fewer people living in residential care recovered their level of function than those living in the community. In Western nations, 10–20 % of hip fracture patients are institutionalised following fracture. Few studies reported impact on participation in domestic, community, social and civic life. Conclusions: Hip fracture has a substantial impact on older peoples’ medium- to longer-term abilities, function, quality of life and accommodation. These studies indicate the range of current outcomes rather than potential improvements with different interventional approaches. Future studies should measure impact on life participation and determine the proportion of people that regain their pre-fracture level of functioning to investigate strategies for improving these important outcomes. Keywords: Hip fracture, Recovery of function, Mobility limitation, Activities of daily living, Institutionalisation, Quality of life, Osteoporosis, Aged, Longterm care, Review Abbreviations: ADL, Activities of daily living; HR, Hazard ratio; IADL, Instrumental activities of daily living; ICF, International classification of functioning, disability and health; OR, Odds ratio; QALY, Quality adjusted life year; QOL, Quality of life; US, United States; WHO, World Health Organizatio

Patterns of medication prescription by dementia diagnosis in Australian nursing home residents: a cross‐sectional study

© 2019 The Society of Hospital Pharmacists of Australia This author accepted manuscript is made available following 12 month embargo from date of publication (March 2019) in accordance with the publisher’s archiving policyCurrent information on the patterns of medication use in nursing home residents living with dementia is conflicting. The aim of this study was to investigate medication use and its associations with dementia diagnosis in Australian nursing home residents

Pathogenicity and immunogenicity of attenuated, nef-deleted HIV-1 strains in vivo

In efforts to develop an effective vaccine, sterilizing immunity to primate lentiviruses has only been achieved by the use of live attenuated viruses carrying major deletions in nef and other accessory genes. Although live attenuated HIV vaccines are unlikely to be developed due to a myriad of safety concerns, opportunities exist to better understand the correlates of immune protection against HIV infection by studying rare cohorts of long-term survivors infected with attenuated, nef-deleted HIV strains such as the Sydney blood bank cohort (SBBC). Here, we review studies of viral evolution, pathogenicity, and immune responses to HIV infection in SBBC members. The studies show that potent, broadly neutralizing anti-HIV antibodies and robust CD8+ T-cell responses to HIV infection were not necessary for long-term control of HIV infection in a subset of SBBC members, and were not sufficient to prevent HIV sequence evolution, augmentation of pathogenicity and eventual progression of HIV infection in another subset. However, a persistent T-helper proliferative response to HIV p24 antigen was associated with long-term control of infection. Together, these results underscore the importance of the host in the eventual outcome of infection. Thus, whilst generating an effective antibody and CD8+ T-cell response are an essential component of vaccines aimed at preventing primary HIV infection, T-helper responses may be important in the generation of an effective therapeutic vaccine aimed at blunting chronic HIV infection

Using guided individualised feedback to review self-reported quality of life in health and its importance

© 2014 Taylor & Francis. This pilot study investigated the effects of providing guided, individualised feedback on subjective quality of life (QoL), using results from the multidimensional WHOQOL-BREF profile. Participants (n=129; 85 chronically ill) were recruited in the community, and primary care. They were randomised to receive written or verbal guidance on interpreting a new graphical summary profile, which simultaneously presented (a) their individual self-ratings of QoL and (b) the importance attributed to each QoL dimension. Before and after feedback, participants completed health status, subjective QoL, QoL Importance, goal-oriented QoL and mood measures. Receiving individualised feedback was associated with increased psychological QoL, with modest effect size. No effects were found for physical, social or environmental QoL or QoL importance, health status, mood or goal-oriented QoL. There were no differences between modes of delivering guidance, indicating equal effectiveness. Chronic illness participants reported poorer QoL, moved more slowly towards their QoL goals, and had larger differences between core QoL and QoL Importance than healthy participants. Guided individualised empirical feedback about QoL judgements could be used to promote psychological well-being. Although professional interpretation of feedback is unnecessary, if shared, patients’ profiled WHOQOL information could support self-monitoring, self-management and clinical decision-making