Polypharmacy Is Significantly and Positively Associated with the Frailty Status Assessed Using the 5-Item FRAIL Scale, Cardiovascular Health Phenotypic Classification of Frailty Index, and Study of Osteoporotic Fractures Scale

The aim of this study was to investigate the association between frailty and polypharmacy using three different frailty screening tools. This was a cross-sectional study of people aged ≥65 years. Participants were included and interviewed using questionnaires. Polypharmacy was defined as the daily use of eight or more pills. Frailty was assessed using a screening tool, including (1) the Fatigue, Resistance, Ambulation, Illness and Loss of Weight Index (5-item FRAIL scale), (2) the Cardiovascular Health Phenotypic Classification of Frailty (CHS_PCF) index (Fried’s Frailty Phenotype), and (3) the Study of Osteoporotic Fracture (SOF) scale. A total of 205 participants (mean age: 71.1 years; 53.7% female) fulfilled our inclusion criteria. The proportion of patients with polypharmacy was 14.1%. After adjustments were made for comorbidity or potential confounders, polypharmacy was associated with frailty on the 5-item FRAIL scale (adjusted odds ratio [aOR]: 9.12; 95% confidence interval [CI]: 3.6–23.16), CHS_PCF index (aOR: 8.98; 95% CI: 2.51–32.11), and SOF scale (aOR: 6.10; 95% CI: 1.47–25.3). Polypharmacy was associated with frailty using three frailty screening tools. Future research is required to further enhance our understanding of the risk of frailty among older adults.

Association of Initial Maximal Motor Ability With Long-term Functional Outcome in Patients With COL6-Related Dystrophies

ObjectiveTo accurately categorize the phenotypes of individuals with collagen VI–related dystrophies (COL6-RDs) during the first years of life to predict long-term motor function and pulmonary function, to provide phenotype-specific anticipatory care, and to improve clinical trial readiness.MethodsThis retrospective, multicenter, international study analyzed the relationship of long-term motor and pulmonary function with the initial maximal motor ability achieved in individuals with COL6-RD.ResultsWe studied 119 patients with COL6-RD from Spain (n = 54) and the United States (n = 65). The early maximal motor milestones of ability to rise from the floor unassisted and ability to climb 4 steps without holding onto a railing demonstrated reliability in distinguishing between 3 COL6-RD phenotypic subgroups: (1) Ullrich congenital muscular dystrophy, (2) intermediate COL6-RD, and (3) Bethlem myopathy. Long-term motor function and pulmonary function are strongly correlated with the maximal motor ability achieved during the first years of life. Maximal motor capacity can predict other disease-relevant events such as the age at loss of ambulation and the need for the initiation of nocturnal noninvasive ventilation.ConclusionThis work proposes a prospective phenotypic classification for COL6-RDs that will enable an accurate prediction of a patient's COL6-RD phenotype during the first years of life. The ability to establish a patient's COL6-RD phenotypic classification early will enable a more accurate prognosis of future motor and pulmonary function, thus improving anticipatory clinical care, and it will be instrumental in aiding the design of future clinical trials by allowing early stratification of trial cohorts.

Phenotypic classification of asthma based on a new Type 2‐high and Type 2‐low endotypic classification: It all began with Rackemann

Background: Asthma is now recognized as a heterogeneous collection of disease entities associated with different clinical phenotypic presentations and diverse endotypic mechanisms. Recently, a new system of nomenclature of asthma has evolved by using a type 2 (T2) high and T2-low endotypic classification that has proven useful for diagnosis and for choosing the right biologic for patients with asthma. Aim: The purpose of this report was to provide an overview of molecular endotypes, asthma phenotypes, and existing biomarkers, with a focus on the new classification system of T2 and non-T2 pathways in the historical context of the contributions of Francis M. Rackemann, M.D., that set the stage both for our current understanding of the spectrum of disease entities of asthma and for the basis for the use of emerging biologics for the treatment of these disorders. Methods: This article was based on literature review of PubMed and the author’s own research and clinical experiences. Results: Currently, the therapy for asthma is being directed to a treatment strategy based on patient-specific phenotypic characteristics and underlying endotypic mechanisms of tissue injury that focus on a T2-high and T2-low airway inflammation classification. Based on this classification, the clinician is provided with a useful treatment stratagem for choosing the right biologic for personalized care of patients with asthma. Although not perfect in its total applicability, it affords a guide in helping to choose among the currently available biologics, the most appropriate one, as well as those that inevitably will become available. Conclusion: The phenotypic classification of asthma described in this report began with the clinical observations that were made by of an astute clinician long before the supernova emergence of information related to T2-high and T2-low immune function. Rackemann’s legacy to clinical allergy practice once again illustrates that science and technology can best progress through the energizing force of clinical observation.

Use of a rare disease registry for establishing phenotypic classification of previously unassigned GLA variants: a consensus classification system by a multispecialty Fabry disease genotype–phenotype workgroup

BackgroundFabry disease (α-galactosidase deficiency) is an X-linked genetic disease caused by a variety of pathogenic GLA variants. The phenotypic heterogeneity is considerable, with two major forms, classic and later-onset disease, but adjudication of clinical phenotype is currently lacking for many variants. We aimed to determine consensus phenotypic classification for previously unclassified GLA variants from the GLA-specific fabry-database.org database.MethodsA Fabry disease genotype–phenotype workgroup developed a five-stage iterative system based on expert clinical assessment, published literature and clinical evidence of pathogenicity using a 2-point scoring system based on clinical hallmarks of classic disease. Kaplan–Meier (KM) analysis of severe clinical event-free survival was used as final validation. Results were compared with those from web-based disease databases and in silico pathogenicity prediction programmes.ResultsFinal consensus on classifications of ‘pathogenic’ was achieved for 32 of 33 GLA variants (26 ‘classic’ phenotype, 171 males; 6 ‘later-onset’ phenotype, 57 males). One variant remained of uncertain significance. KM curves were similar for the known fabry-database.org database phenotypes and when workgroup consensus classifications were added, and the curves retained the same separation between ‘classic’ and ‘later-onset’ phenotypes.ConclusionThe iterative system implemented by a Fabry disease genotype–phenotype workgroup achieved phenotypic classifications for variants that were previously unclassified. Clinical pathogenicity associated with a particular GLA variant defined in affected males appears to have predictive value and also generally correlates with risk for affected females. The newly established classifications can be of benefit to the clinical care of Fabry patients harbouring these variants.

Phenotypic classification of asthma based on a new Type 2–high and Type 2–low endotypic classification: It all began with Rackemann

Background: Asthma is now recognized as a heterogeneous collection of disease entities associated with different clinical phenotypic presentations and diverse endotypic mechanisms. Recently, a new system of nomenclature of asthma has evolved by using a type 2 (T2) high and T2-low endotypic classification that has proven useful for diagnosis and for choosing the right biologic for patients with asthma.Aim: The purpose of this report was to provide an overview of molecular endotypes, asthma phenotypes, and existing biomarkers,with a focus on the new classification system of T2 and non-T2 pathways in the historical context of the contributionsof Francis M. Rackemann, M.D., that set the stage both for our current understanding of the spectrum of disease entities of asthma and for the basis for the use of emerging biologics for the treatment of these disorders.Methods: This article was based on literature review of PubMed and the author’s own research and clinical experiences.Results: Currently, the therapy for asthma is being directed to a treatment strategy based on patient-specific phenotypic characteristics and underlying endotypic mechanisms of tissue injury that focus on a T2-high and T2-low airway inflammation classification. Based on this classification, the clinician is provided with a useful treatment stratagem for choosing the right biologic for personalized care of patients with asthma. Although not perfect in its total applicability, it affords a guide in helping to choose among the currently available biologics, the most appropriate one, as well as those that inevitably will become available.Conclusion: The phenotypic classification of asthma described in this report began with the clinical observations that weremade by of an astute clinician long before the supernova emergence of information related to T2-high and T2-low immunefunction. Rackemann’s legacy to clinical allergy practice once again illustrates that science and technology can best progressthrough the energizing force of clinical observation.