Beers criteria to identify the consumption of potentially inappropriate medication: Adaptation for its application in Argentina

Introducción. Los Criterios de Beers son los más utilizados para evaluar el uso de medicación potencialmente inapropiada en grandes poblaciones, pero no contemplan algunos medicamentos de uso frecuente fuera de los EE.UU. Objetivo. Realizar una adaptación al contexto de Argentina de los Criterios de Beers publicados en 2019. Métodos. Fue elaborada una lista preliminar de medicación potencialmente inapropiada adaptada a la comercialización local, que luego fue consensuada por un panel de expertos (método Delphi). Resultados. De los 112 medicamentos originales listados en la tabla dos de los Criterios de Beers (en forma individual o como grupo), fueron excluidos 36 por no estar disponibles en Argentinae el país y fueron sumados 23 que no se comercializan en los EE.UU. pero sí en Argentina. Luego de dos rondas y de consensuar la suma a esta lista de dos grupos farmacológicos (antimigrañosos y vasodilatadores periféricos), fue acordado el agregado de picosulfato, bisacodilo, senósidos y cáscara sagrada como medicación potencialmente inapropiada en el grupo de agentes contra el estreñimiento, la fluoxetina entre los inhibidores selectivos de la recaptación de serotonina y el Gingko biloba como droga contra la demencia. También hubo consenso en advertir el riesgo de hipotensión ortostática asociado a la tamsulosina, en aconsejar la consideración de la carga anticolinérgica total del esquema terapéutico administrado y en recomendar al paracetamol como primera línea de tratamiento del dolor, asociado o no a opioides. Conclusiones. Contar con una versión de los Criterios de Beers 2019 adaptada al contexto de Argentina contribuirá al desarrollo y monitoreo de intervenciones para prevenir y reducir el consumo de medicación potencialmente inapropiada.Introduction. The Beers Criteria is the most widely used criteria to assess the use of potentially inappropriate medication in large populations, but they do not include some medications that are frequently used outside the United States. Objective. To make an adaptation of the Beers Criteria published in 2019 to the context of Argentina. Methods. A preliminary list of potentially inappropriate medication adapted to local market and practice was designed, which was then agreed upon by a panel of experts (Delphi method). Results. Of the 112 original drugs in the table 2 of the Beers Criteria (individually or as a group), 36 were excluded because they were not available in Argentina and 23 locally marketed drugs but not in the US were included. After two rounds and agreeing to add two additional pharmacological groups to this list (antimigraine and peripheral vasodilators), it was decided to add picosulfate, bisacodyl, sennosides and cascara sagrada as potentially inappropriate medication in the group of anti-constipation agents, fluoxetine among the selective serotonin reuptake inhibitors and Ginkgo biloba as an antidementia drug. There was also consensus in warning about the risk of orthostatic hypotension associated with tamsulosin, in advising consideration of the total anticholinergic load of the therapeutic regimen administered, and in recommending paracetamol as the first line of pain treatment, associated or not with opioids. Conclusions. Having a version of the Beers Criteria 2019 adapted to the Argentine context will contribute to the development and monitoring of interventions to prevent and reduce the consumption of potentially inappropriate medication.Fil: Calabro, Pablo. Hospital Italiano; ArgentinaFil: Donniani, Ileana. Hospital Italiano; ArgentinaFil: Bellomo, Maria Jose. Hospital Italiano; ArgentinaFil: Mozeluk, Natalia. Hospital Italiano; ArgentinaFil: Elizondo, Cristina María. Hospital Italiano; ArgentinaFil: Perman, Gastón. Hospital Italiano; ArgentinaFil: Schapira, Marcelo. Hospital Italiano; ArgentinaFil: Gibert, Marcela Fabiana. Hospital Italiano; ArgentinaFil: Terrasa, Sergio Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano. Instituto Universitario. Escuela de Medicina; Argentin

Gait disorders are associated with non-cardiovascular falls in elderly people: a preliminary study

BACKGROUND: The association between unexplained falls and cardiovascular causes is increasingly recognized. Neurally mediated cardiovascular disorders and hypotensive syndromes are found in almost 20 percent of the patients with unexplained falls. However, the approach to these patients remains unclear. Gait assessment might be an interesting approach to these patients as clinical observations suggests that those with cardiovascular or hypotensive causes may not manifest obvious gait alterations. Our primary objective is to analyze the association between gait disorders and a non-cardiovascular cause of falls in patients with unexplained falls. A second objective is to test the sensitivity and specificity of a gait assessment approach for detecting non-cardiovascular causes when compared with intrinsic-extrinsic classification. METHODS: Cross-sectional study performed in a falls clinic at a university hospital in 41 ambulatory elderly participants with unexplained falls. Neurally mediated cardiovascular conditions, neurological diseases, gait and balance problems were assessed. Gait disorder was defined as a gait velocity < 0.8 m/s or Tinetti Gait Score <9. An attributable etiology of the fall was determined in each participant. Comparisons between the gait assessment approach and the attributable etiology regarding a neurally mediated cardiovascular cause were performed. Fisher exact test was used to test the association hypothesis. Sensitivity and specificity of gait assessment approach and intrinsic-extrinsic classification to detect a non-cardiovascular mediated fall was calculated with 95% confidence intervals (CI95%). RESULTS: A cardiovascular etiology (orthostatic and postprandial hypotension, vasovagal syndrome and carotid sinus hypersensitivity) was identified in 14% of participants (6/41). Of 35 patients with a gait disorder, 34 had a non-cardiovascular etiology of fall; whereas in 5 out of 6 patients without a gait disorder, a cardiovascular diagnosis was identified (p < 0.001). Sensitivity and specificity of the presence of gait disorder for identifying a non-cardiovascular mediated cause was 97.1% (CI95% = 85–99) and 83% (CI95% = 36–99), respectively. CONCLUSION: In community dwelling older persons with unexplained falls, gait disorders were associated with non-cardiovascular diagnosis of falls. Gait assessment was a useful approach for the detection of a non-cardiovascular mediated cause of falls, providing additional value to this assessment

Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis

Objectives:To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease.Methods:A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated for bilateral caudate and putamen for each case. The right:left asymmetry index and striatal asymmetry index was calculated.Results:Scans were available from 37 cases of monogenetic Parkinson's disease (7 glucocerebrosidase (GBA) mutations, 8 alpha-synuclein, 3 LRRK2, 7 PINK1, 12 Parkin). The asymmetry of radioligand uptake for Parkinson's disease with GBA or LRRK2 mutations was greater than that for Parkinson's disease with alpha synuclein, PINK1 or Parkin mutations.Conclusions:The asymmetry of radioligand uptake in Parkinsons disease associated with GBA or LRRK2 mutations suggests that interactions with additional genetic or environmental factors may be associated with dopaminergic neuronal loss

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Association of Dual-Task Gait With Incident Dementia in Mild Cognitive Impairment

Importance Gait performance is affected by neurodegeneration in aging and has the potential to be used as a clinical marker for progression from mild cognitive impairment (MCI) to dementia. A dual-task gait test evaluating the cognitive-motor interface may predict dementia progression in older adults with MCI. Objective To determine whether a dual-task gait test is associated with incident dementia in MCI. Design, Setting, and Participants The Gait and Brain Study is an ongoing prospective cohort study of community-dwelling older adults that enrolled 112 older adults with MCI. Participants were followed up for 6 years, with biannual visits including neurologic, cognitive, and gait assessments. Data were collected from July 2007 to March 2016. Main Outcomes and Measures Incident all-cause dementia was the main outcome measure, and single- and dual-task gait velocity and dual-task gait costs were the independent variables. A neuropsychological test battery was used to assess cognition. Gait velocity was recorded under single-task and 3 separate dual-task conditions using an electronic walkway. Dual-task gait cost was defined as the percentage change between single- and dual-task gait velocities: ([single-task gait velocity – dual-task gait velocity]/ single-task gait velocity) × 100. Cox proportional hazard models were used to estimate the association between risk of progression to dementia and the independent variables, adjusted for age, sex, education, comorbidities, and cognition. Results Among 112 study participants with MCI, mean (SD) age was 76.6 (6.9) years, 55 were women (49.1%), and 27 progressed to dementia (24.1%), with an incidence rate of 121 per 1000 person-years. Slow single-task gait velocity (P = .05)while high dual-task gait cost while counting backward (HR, 3.79; 95% CI, 1.57-9.15; P = .003) and naming animals (HR, 2.41; 95% CI, 1.04-5.59; P = .04) were associated with dementia progression (incidence rate, 155 per 1000 person-years). The models remained robust after adjusting by baseline cognition except for dual-task gait cost when dichotomized. Conclusions and Relevance Dual-task gait is associated with progression to dementia in patients with MCI. Dual-task gait testing is easy to administer and may be used by clinicians to decide further biomarker testing, preventive strategies, and follow-up planning in patients with MCI

Association of Dual-Task Gait With Incident Dementia in Mild Cognitive Impairment: Results From the Gait and Brain Study.

Importance: Gait performance is affected by neurodegeneration in aging and has the potential to be used as a clinical marker for progression from mild cognitive impairment (MCI) to dementia. A dual-task gait test evaluating the cognitive-motor interface may predict dementia progression in older adults with MCI. Objective: To determine whether a dual-task gait test is associated with incident dementia in MCI. Design, Setting, and Participants: The Gait and Brain Study is an ongoing prospective cohort study of community-dwelling older adults that enrolled 112 older adults with MCI. Participants were followed up for 6 years, with biannual visits including neurologic, cognitive, and gait assessments. Data were collected from July 2007 to March 2016. Main Outcomes and Measures: Incident all-cause dementia was the main outcome measure, and single- and dual-task gait velocity and dual-task gait costs were the independent variables. A neuropsychological test battery was used to assess cognition. Gait velocity was recorded under single-task and 3 separate dual-task conditions using an electronic walkway. Dual-task gait cost was defined as the percentage change between single- and dual-task gait velocities: ([single-task gait velocity - dual-task gait velocity]/ single-task gait velocity) × 100. Cox proportional hazard models were used to estimate the association between risk of progression to dementia and the independent variables, adjusted for age, sex, education, comorbidities, and cognition. Results: Among 112 study participants with MCI, mean (SD) age was 76.6 (6.9) years, 55 were women (49.1%), and 27 progressed to dementia (24.1%), with an incidence rate of 121 per 1000 person-years. Slow single-task gait velocity ( Conclusions and Relevance: Dual-task gait is associated with progression to dementia in patients with MCI. Dual-task gait testing is easy to administer and may be used by clinicians to decide further biomarker testing, preventive strategies, and follow-up planning in patients with MCI. Trial Registration: clinicaltrials.gov: NCT03020381