Identifying and linking prosthetic outcomes to the ICF framework: a step to inform the benefits measured in prosthetic health economic evaluations.

PURPOSE: Prosthetic research seems focused on measuring gait-related outcomes that may not adequately measure real-world benefits of prosthetic interventions. Systematically cataloguing a comprehensive range of outcomes is an important steppingstone towards developing a holistic way to measure the benefits of prosthetic interventions for future health economic evaluations. The purpose of this research was to identify and catalogue the outcomes measured in lower-limb prosthetic research using the International Classification of Functioning, Disability, and Health (ICF) framework and a custom clinical framework, and thereby describe the existing research focus and identify evidence gaps. MATERIALS AND METHODS: A structured literature search identified systematic reviews of lower-limb prosthetic interventions. Reported outcomes were extracted from included studies and linked to the ICF- and clinical-frameworks. RESULTS: Of the 1297 extracted outcomes, 1060 were linked to the ICF framework. Most outcomes linked to second- (63.8%) or third-level categories (33.4%), such as Gait Pattern Functions (b770, 49.8%). Most of these outcomes (31.2%) describe temporospatial, kinematic or kinetic gait measures as categorised by the clinical framework. CONCLUSIONS: Lower-limb prosthetic research is focused on laboratory-based measures of gait. There are evidence gaps describing participation in real-world activities - important outcomes to inform policy and investment decisions that determine the prosthetic interventions available for people with limb-loss.Implications for rehabilitationCataloguing the outcomes used in prosthetic research to the International Classification of Functioning, Disability, and Health (ICF) allows important evidence gaps to be illuminated given the holistic description of function and disability.Establishing a comprehensive list of prosthetic outcomes, described using an internationally recognised framework with unified and consistent language, is an important steppingstone towards developing a core outcome set (COS) for prosthetic interventions and informing the benefits measured in future prosthetic health economic evaluations (HEEs).Being able to measure the benefits of a prosthesis that are most important to prosthesis users and funders has potential to fundamentally change future HEEs that influence funding policies, and ultimately the prostheses made available to people living with limb-loss.

Factors Associated With Health-Related Quality of Life in People Living With Partial Foot or Transtibial Amputation.

OBJECTIVES: To determine which demographic, amputation, and health-related factors were associated with health-related quality of life (HR-QoL) in people living with partial foot amputation (PFA) or transtibial amputation (TTA). DESIGN: Cross-sectional survey. SETTING: Community. PARTICIPANTS: Adults (N=123) with unilateral PFA (n=42) or TTA (n=81). INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: Medical Outcome Short Form (SF-36) version 2. RESULTS: Variation in the SF-36 Physical or Mental Component Summary scores were associated with complex interactions between factors, including: time since amputation, fatigue, anxiety, depression, pain interference, and physical function. Level of amputation (ie, PFA or TTA) did not explain a significant part of the variation in either the SF-36 Physical or Mental Component Summary scores. CONCLUSIONS: Given the complex interactions between factors associated with the physical and mental health components of HR-QoL, there are opportunities to consider the long-term holistic care required by people living in the community with PFA or TTA.

Identification and SAR of novel diaminopyrimidines. Part 2: The discovery of RO-51, a potent and selective, dual P2X(3)/P2X(2/3) antagonist for the treatment of pain.

The purinoceptor subtypes P2X(3) and P2X(2/3) have been shown to play a pivotal role in models of various pain conditions. Identification of a potent and selective dual P2X(3)/P2X(2/3) diaminopyrimidine antagonist RO-4 prompted subsequent optimization of the template. This paper describes the SAR and optimization of the diaminopyrimidine ring and particularly the substitution of the 2-amino group. The discovery of the highly potent and drug-like dual P2X(3)/P2X(2/3) antagonist RO-51 is presented.

Identification and SAR of novel diaminopyrimidines. Part 1: The discovery of RO-4, a dual P2X(3)/P2X(2/3) antagonist for the treatment of pain.

P2X purinoceptors are ligand-gated ion channels whose endogenous ligand is ATP. Both the P2X(3) and P2X(2/3) receptor subtypes have been shown to play an important role in the regulation of sensory function and dual P2X(3)/P2X(2/3) antagonists offer significant potential for the treatment of pain. A high-throughput screen of the Roche compound collection resulted in the identification of a novel series of diaminopyrimidines; subsequent optimization resulted in the discovery of RO-4, a potent, selective and drug-like dual P2X(3)/P2X(2/3) antagonist.