The Lower Limb Functional Index: development and clinimetric properties

Background Existing lower-limb, region-specific, patient-reported outcome measures have clinimetric limitations, including limitations in psychometric characteristics (eg, lack of internal consistency, lack of responsiveness, measurement error) and the lack of reported practical and general characteristics. A new patient-reported outcome measure, the Lower Limb Functional Index (LLFI), was developed to address these limitations. Objective The purpose of this study was to overcome recognized deficiencies in existing lower-limb, region-specific, patient-reported outcome measures through: (1) development of a new lower-extremity outcome scale (ie, the LLFI) and (2) evaluation of the clinimetric properties of the LLFI using the Lower Extremity Functional Scale (LEFS) as a criterion measure. Design This was a prospective observational study. Methods The LLFI was developed in a 3-stage process of: (1) item generation, (2) item reduction with an expert panel, and (3) pilot field testing (n=18) for reliability, responsiveness, and sample size requirements for a larger study. The main study used a convenience sample (n=127) from 10 physical therapy clinics. Participants completed the LLFI and LEFS every 2 weeks for 6 weeks and then every 4 weeks until discharge. Data were used to assess the psychometric, practical, and general characteristics of the LLFI and the LEFS. The characteristics also were evaluated for overall performance using the Measurement of Outcome Measures and Bot clinimetric assessment scales. Results The LLFI and LEFS demonstrated a single-factor structure, comparable reliability (intraclass correlation coefficient [2,1]=.97), scale width, and high criterion validity (Pearson r=.88, with 95% confidence interval [CI]). Clinimetric performance was higher for the LLFI compared with the LEFS on the Measurement of Outcome Measures scale (96% and 95%, respectively) and the Bot scale (100% and 83%, respectively). The LLFI, compared with the LEFS, had improved responsiveness (standardized response mean=1.75 and 1.64, respectively), minimal detectable change with 90% CI (6.6% and 8.1%, respectively), and internal consistency (α=.91 and .95, respectively), as well as readability with reduced user error and completion and scoring times. Limitations Limitations of the study were that only participants recruited from outpatient physical therapy clinics were included and that no specific conditions or diagnostic subgroups were investigated. Conclusion The LLFI demonstrated sound clinimetric properties. There was lower response error, efficient completion and scoring, and improved responsiveness and overall performance compared with the LEFS. The LLFI is suitable for assessment of lower-limb function.

Expanding the cone location and magnitude index to include corneal thickness and posterior surface information for the detection of keratoconus

PURPOSE To extend the capabilities of the Cone Location and Magnitude Index algorithm to include a combination of topographic information from the anterior and posterior corneal surfaces and corneal thickness measurements to further improve our ability to correctly identify keratoconus using this new index: ConeLocationMagnitudeIndex_X. DESIGN Retrospective case-control study. METHODS Three independent data sets were analyzed: 1 development and 2 validation. The AnteriorCornealPower index was calculated to stratify the keratoconus data from mild to severe. The ConeLocationMagnitudeIndex algorithm was applied to all tomography data collected using a dual Scheimpflug-Placido-based tomographer. The ConeLocationMagnitudeIndex_X formula, resulting from analysis of the Development set, was used to determine the logistic regression model that best separates keratoconus from normal and was applied to all data sets to calculate PercentProbabilityKeratoconus_X. The sensitivity/specificity of PercentProbabilityKeratoconus_X was compared with the original PercentProbabilityKeratoconus, which only uses anterior axial data. RESULTS The AnteriorCornealPower severity distribution for the combined data sets are 136 mild, 12 moderate, and 7 severe. The logistic regression model generated for ConeLocationMagnitudeIndex_X produces complete separation for the Development set. Validation Set 1 has 1 false-negative and Validation Set 2 has 1 false-positive. The overall sensitivity/specificity results for the logistic model produced using the ConeLocationMagnitudeIndex_X algorithm are 99.4% and 99.6%, respectively. The overall sensitivity/specificity results for using the original ConeLocationMagnitudeIndex algorithm are 89.2% and 98.8%, respectively. CONCLUSIONS ConeLocationMagnitudeIndex_X provides a robust index that can detect the presence or absence of a keratoconic pattern in corneal tomography maps with improved sensitivity/specificity from the original anterior surface-only ConeLocationMagnitudeIndex algorithm.

Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure.

Prior research has shown that mothers with Interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) report greater difficulty in parenting their toddlers. Relative to their frequent early exposure to violence and maltreatment, these mothers display dysregulation of their hypothalamic pituitary adrenal axis (HPA-axis), characterized by hypocortisolism. Considering methylation of the promoter region of the glucocorticoid receptor gene NR3C1 as a marker for HPA-axis functioning, with less methylation likely being associated with less circulating cortisol, the present study tested the hypothesis that the degree of methylation of this gene would be negatively correlated with maternal IPV-PTSD severity and parenting stress, and positively correlated with medial prefrontal cortical (mPFC) activity in response to video-stimuli of stressful versus non-stressful mother-child interactions. Following a mental health assessment, 45 mothers and their children (ages 12-42 months) participated in a behavioral protocol involving free-play and laboratory stressors such as mother-child separation. Maternal DNA was extracted from saliva. Interactive behavior was rated on the CARE-Index. During subsequent fMRI scanning, mothers were shown films of free-play and separation drawn from this protocol. Maternal PTSD severity and parenting stress were negatively correlated with the mean percentage of methylation of NR3C1. Maternal mPFC activity in response to video-stimuli of mother-child separation versus play correlated positively to NR3C1 methylation, and negatively to maternal IPV-PTSD and parenting stress. Among interactive behavior variables, child cooperativeness in play was positively correlated with NR3C1 methylation. Thus, the present study is the first published report to our knowledge, suggesting convergence of behavioral, epigenetic, and neuroimaging data that form a psychobiological signature of parenting-risk in the context of early life stress and PTSD.