Comprehensive Quantitative Spatiotemporal Gait Analysis Identifies Gait Characteristics for Early Dementia Subtyping in Community Dwelling Older Adults

Background: Recent studies associated gait patterns with cognitive impairment stages. The current study examined the relation between dementia type and spatiotemporal gait characteristics under different walking conditions in pre and mild neurocognitive disorder stage.Methods: Community-dwelling older adults (age 50+) with memory complaints consulting a memory clinic underwent, at baseline and during follow-up (every 4 months), a standard dementia assessment and a comprehensive spatiotemporal gait analysis [walking on an electronic walkway at usual pace (UP) with and without a counting-backwards (CW) or animal-reciting dual-task (AW), at fast (FP) and at slow (SP) pace]. At baseline the participants were categorized according to the Clinical Dementia Rating (CDR) scale. At the end of the study, the dementia diagnosis was used to stratify the categories in three outcome groups: developed “No-dementia,” “AD+FTD” (grouping Alzheimer's or Fronto-temporal dementia) or “VascD+LBD” dementia (grouping Vascular dementia or Lewy body dementia). The gait characteristics were compared per category in paired groups. Sub-analyzing in the ≥70-years-old participants evaluated the age effect.Results: Five hundred and thirty-six participants, age 50-to-95-years old were followed for 31-to-41 months. In the CDR 0, no differences were seen between eventual dementia and no-dementia individuals. In the CDR 0.5, CW dual task cost (DTC) step width was larger in the imminent “AD+FTD” and AW (normalized) gait speed was slower in the future “VascD+LBD” group compared to the no-dementia participants. Slower UP (normalized) gait speed differed the future “VascD+LBD” from the “AD+FTD” individuals. In the CDR 1: Wider steps in UP, SP and CW differed the “VascD+LBD” from the “AD+FTD” group. In the ≥70-years old CDR 0 category, higher AW cycle time variability in the imminent “AD+FTD” dementia group, wider UP step width and higher AW cycle time variability in the “VascD+LBD” group differed them from the no-dementia group up to 3 years before dementia diagnosis. The distinctive gait characteristics between the no-dementia and the imminent dementia groups in CDR 0.5 and CDR 1 remained the same as in the overall group. However, no gait differences were found between “VascD+LBD” and “AD+FTD” groups in the pre-dementia stages.Conclusion: Distinctive spatiotemporal gait characteristics were associated with specific dementia types up to 3 years before diagnosis. The association is influenced by the cognitive stage and age

The Development of Recommendations for Healthcare Providers to Support Patients Experiencing Medication Self-Management Problems

Medication self-management problems such as the inability to correctly obtain, understand, organize, administer or monitor medication can result in negative patient outcomes. However, supportive tools for healthcare providers to assist patients with medication self-management problems are lacking. This study aimed to develop recommendations for healthcare providers to support patients with polypharmacy who experience medication self-management problems. A three-phase study was conducted starting with (1) the mapping of medication self-management problems, followed by (2) a scoping review providing a list of relevant interventions and actions for each respective problem and (3) a three-round modified e-Delphi study with experts to reach consensus on the relevance and clarity of the recommended interventions and actions. The cut-off for consensus on the relevance and clarity of the recommendations was set at 80% expert agreement. Experts could propose additional recommendations based on their professional experience and expertise. The experts (n = 23) involved were healthcare professionals (i.e., nurses, pharmacists, and physicians) with specific expertise in medication management of patients with polypharmacy. Simultaneous with the second e-Delphi round, a panel of patients with polypharmacy (n = 8) evaluated the usefulness of recommendations. Results obtained from the patient panel were fed back to the panel of healthcare providers in the third e-Delphi round. Descriptive statistics were used for data analysis. Twenty medication self-management problems were identified. Based on the scoping review, a list of 66 recommendations for healthcare providers to support patients with the identified medication self-management problems was composed. At the end of the three-round e-Delphi study, the expert panel reached consensus on the relevance and clarity of 67 recommendations, clustered according to the six phases of the medication self-management model by Bailey et al. In conclusion, this study resulted in a guidance document including recommendations that can serve as a resource for healthcare providers to support patients with polypharmacy in case of medication self-management problems. Future research should focus on the evaluation of the feasibility and user-friendliness of the guide with recommendations in clinical practice.</p

Motoric Cognitive Risk Syndrome: Multicountry Prevalence and Dementia Risk

OBJECTIVES: Our objective is to report prevalence of motoric cognitive risk syndrome (MCR), a newly described predementia syndrome characterized by slow gait and cognitive complaints, in multiple countries, and its association with dementia risk. METHODS: Pooled MCR prevalence analysis of individual data from 26,802 adults without dementia and disability aged 60 years and older from 22 cohorts from 17 countries. We also examined risk of incident cognitive impairment (Mini-Mental State Examination decline ≥4 points) and dementia associated with MCR in 4,812 individuals without dementia with baseline Mini-Mental State Examination scores ≥25 from 4 prospective cohort studies using Cox models adjusted for potential confounders. RESULTS: At baseline, 2,808 of the 26,802 participants met MCR criteria. Pooled MCR prevalence was 9.7% (95% confidence interval [CI] 8.2%-11.2%). MCR prevalence was higher with older age but there were no sex differences. MCR predicted risk of developing incident cognitive impairment in the pooled sample (adjusted hazard ratio [aHR] 2.0, 95% CI 1.7-2.4); aHRs were 1.5 to 2.7 in the individual cohorts. MCR also predicted dementia in the pooled sample (aHR 1.9, 95% CI 1.5-2.3). The results persisted even after excluding participants with possible cognitive impairment, accounting for early dementia, and diagnostic overlap with other predementia syndromes. CONCLUSION: MCR is common in older adults, and is a strong and early risk factor for cognitive decline. This clinical approach can be easily applied to identify high-risk seniors in a wide variety of settings

Transmitted drug resistance, selection of resistance mutations and moderate antiretroviral efficacy in HIV-2: Analysis of the HIV-2 Belgium and Luxembourg database

BACKGROUND: Guidelines established for the treatment of HIV-1 infection and genotype interpretation do not apply for HIV-2. Data about antiretroviral (ARV) drug efficacy and resistance mutations is scarce. METHODS: Clinical data about HIV-2 infected patients in Belgium and Luxembourg were collected and the effect of ARV therapy on plasma viral load and CD4 counts were analysed. Viral RNA encoding for protease (PR) and reverse transcriptase (RT) from ARV-naive and treated patients were sequenced. RESULTS: Sixty-five HIV-2 infected patients were included in this cohort. Twenty patients were treated with 25 different ARV combinations in a total of 34 regimens and six months after the start of ARV therapy, only one third achieved viral load suppression. All of these successful regimens bar one contained protease inhibitors (PIs). Mean CD4 gains in the group of viral load suppressors and the group of patients treated with PI-containing regimens were respectively significantly higher than in the group of non-suppressors and the group of PI-sparing regimens. The most frequent mutations selected under therapy (compared to HIV-2 ROD) were V71I, L90M and I89V within PR. Within RT, they were M184V, Q151M, V111I and K65R. All of these mutations, except K65R and M184V, were also found in variable proportions in ARV-naive patients. CONCLUSION: Despite a high rate of ARV treatment failure, better virological and immunological results were achieved with PI-containing regimens. The analysis of polymorphic positions and HIV-2 specific mutations selected during therapy showed for the first time that transmission of drug resistant viruses has occurred in Belgium and Luxembourg. The high heterogeneity in ARV combinations reflects a lack of guidelines for the treatment of HIV-2 infection

Guidelines for assessment of gait and reference values for spatiotemporal gait parameters in older adults: The biomathics and canadian gait consortiums initiative

Abstract: Background: Gait disorders, a highly prevalent condition in older adults, are associated with several adverse health consequences. Gait analysis allows qualitative and quantitative assessments of gait that improves the understanding of mechanisms of gait disorders and the choice of interventions. This manuscript aims (1) to give consensus guidance for clinical and spatiotemporal gait analysis based on the recorded footfalls in older adults aged 65 years and over, and (2) to provide reference values for spatiotemporal gait parameters based on the recorded footfalls in healthy older adults free of cognitive impairment and multi-morbidities.Methods: International experts working in a network of two different consortiums (i.e., Biomathics and Canadian Gait Consortium) participated in this initiative. First, they identified items of standardized information following the usual procedure of formulation of consensus findings. Second, they merged databases including spatiotemporal gait assessments with GAITRite® system and clinical information from the “Gait, cOgnitiOn & Decline” (GOOD) initiative and the Generation 100 (Gen 100) study. Only healthy—free of cognitive impairment and multi-morbidities (i.e., ≤ 3 therapeutics taken daily)—participants aged 65 and older were selected. Age, sex, body mass index, mean values, and coefficients of variation (CoV) of gait parameters were used for the analyses. Results: Standardized systematic assessment of three categories of items, which were demographics and clinical information, and gait characteristics (clinical and spatiotemporal gait analysis based on the recorded footfalls), were selected for the proposed guidelines. Two complementary sets of items were distinguished: a minimal data set and a full data set. In addition, a total of 954 participants (mean age 72.8 ± 4.8 years, 45.8% women) were recruited to establish the reference values. Performance of spatiotemporal gait parameters based on the recorded footfalls declined with increasing age (mean values and CoV) and demonstrated sex differences (mean values). Conclusions: Based on an international multicenter collaboration, we propose consensus guidelines for gait assessment and spatiotemporal gait analysis based on the recorded footfalls, and reference values for healthy older adults

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]