Measures Of Function Research Articles

Vestibular Rehabilitation: Improving Symptomatic and Functional Outcomes of Persons with Vestibular Schwannoma: A Systematic Review.

Persons with vestibular schwannoma suffer from dizziness, imbalance, and decreased function leading to reduced quality of life. Other forms of peripheral vestibular hypofunction show improvements in these signs and symptoms with vestibular rehabilitation; however, the efficacy of this intervention for those with vestibular schwannoma is unknown. Therefore, the aim of this systematic review was to determine the effect of vestibular physical therapy on subjective and objective measures of vestibular symptoms and function in people with vestibular schwannoma. Four electronic databases were searched: PubMed, CINAHL, EMBASE, and Cochrane. Included studies were experimental or observational in design and featured patients with vestibular schwannoma who had undergone vestibular physical therapy. Screening and quality assessment was completed independently by 2 researchers. Risk of bias was assessed with a tool appropriate for study design (eg, Cochrane Risk of Bias 2.0 tool for randomized trials). The Grading of Recommendations Assessment, Development and Evaluation approach was used to synthesize findings. Twenty-three studies were included. Overall, the effect of vestibular physical therapy for patients with vestibular schwannoma was uncertain. Outcomes of dizziness, static and dynamic balance, and vestibular function all showed very low certainty on the Grading of Recommendations Assessment, Development and Evaluation assessment. Multimodal physical therapist interventions consistent with clinical practice guidelines (eg, gaze stability, habituation, balance training, gait training) demonstrated potential for improvement in dizziness, balance, and vestibular function, respectively. Results were mostly insignificant when a single modality was used. There may be benefit in multimodal vestibular physical therapy for people with vestibular schwannoma to improve symptoms and function. More high-quality studies specific to vestibular schwannoma prehabilitation and rehabilitation are needed to increase the certainty in the evidence. Physical therapists are encouraged to use multimodal vestibular rehabilitation for vestibular schwannoma in clinical practice in line with clinical guidelines for peripheral vestibular hypofunction.

Predictors of Complete Oral Intake in Patients With Stroke After Tracheostomy.

Tracheostomy procedures inhibit swallowing, although details of subsequent recovery of oral intake remain unknown. This retrospective cohort study aimed to investigate factors influencing dysphagia improvement in patients with subacute stroke after tracheostomy. The study included 117 patients who underwent tracheostomy after subacute stroke, cerebral hemorrhage, or endogenous subarachnoid hemorrhage and received care at 2 convalescent rehabilitation wards in urban and suburban Japan between 2015 and 2022. The primary outcome measure was the achievement of complete oral intake. Patient demographics, Functional Independence Measure scores, body mass index, food intake level scale scores, and the presence of severe white matter hyperintensities on imaging were retrospectively collected from medical records. Statistical analysis involved univariate logistic regression to identify potential predictors and multivariate logistic regression to refine the model while accounting for multicollinearity. In total, 47% of patients achieved complete oral intake on discharge. Sex, days from onset to admission, Functional Independence Measure motor and cognitive scores, body mass index, food intake level scale scores, and severe white matter hyperintensities were identified as potential predictors in the univariate analysis. However, multivariate logistic regression identified only food intake level scale scores (odds ratio [OR], 3.687 [95% CI, 1.519-8.949]; P=0.004) and severe white matter hyperintensities (OR, 0.302 [95% CI, 0.096-0.956]; P=0.042) as significant predictors of complete oral intake. In patients with subacute stroke undergoing tracheostomy, the level of oral intake on admission and severe white matter hyperintensities on imaging may be better predictors of complete oral intake. However, prospective studies with larger sample sizes and more comprehensive data are warranted to confirm these findings.

Influence of Sensory Monitoring on Speech Breathing Planning Processes: An Exploratory Study in Aging Speakers Reporting Dyspnea.

Previous studies have suggested that inspirations during speech pauses are influenced by the length of adjacent utterances, owing to respiratory motor planning and physiological recovery processes. The goal of this study was to examine how attention to respiratory sensations may influence these processes in aging speakers with dyspnea, by measuring the effect of sensory monitoring on the relationship between utterance length and the occurrence of inspirations, as well as on functional voice and respiratory measures. Seventeen adults aged 50 years and older with complaints of voicing-related dyspnea completed a repeated-measures protocol consisting of a 2-week baseline phase and a 4-week sensory monitoring phase. Audiovisual recordings of semistructured speech and self-report questionnaires were collected at study onset, after the baseline phase, and after the sensory monitoring phase. Repeated-measures logistic regressions were conducted to examine changes in the relationship between utterance length and the occurrence of inspirations in adjacent pauses, and repeated-measures analyses of variance were used to investigate any changes in functional voice and respiratory measures. Planning and recovery processes appeared to remain constant across the baseline phase. From postbaseline to postsensory monitoring timepoints, a strengthening of the relationship between the presence of an inspiration during a speech pause and the length of the subsequent-but not preceding-utterance was noted. Significant improvements were noted in voice-related handicap from study onset to postsensory monitoring, but no changes were reported in respiratory comfort during speech. Results suggest that respiratory planning processes, that is, the ability to plan breath intakes based on the length of upcoming utterances, may be modifiable behaviorally through targeted sensory monitoring. Further studies are warranted to validate the proposed role of respiratory sensation awareness in achieving skilled temporal coordination between voicing and breathing.

Serum dysregulation of serine and glycine metabolism as predictive biomarker for cognitive decline in frail elderly subjects

Frailty is a common age-related clinical syndrome characterized by a decline in the function of multiple organ systems, increased vulnerability to stressors, and a huge socio-economic burden. Despite recent research efforts, the physiopathological mechanisms underlying frailty remain elusive and biomarkers able to predate its occurrence in the early stages are still lacking. Beyond its physical component, cognitive decline represents a critical domain of frailty associated with higher risk of adverse health outcomes. We measured by High-Performance Liquid Chromatography (HPLC) a pool of serum amino acids including L-glutamate, L-aspartate, glycine, and D-serine, as well as their precursors L-glutamine, L-asparagine, and L-serine in a cohort of elderly subjects encompassing the entire continuum from fitness to frailty. These amino acids are known to orchestrate excitatory and inhibitory neurotransmission, and in turn, to play a key role as intermediates of energy homeostasis and in liver, kidney, muscle, and immune system metabolism. To comprehensively assess frailty, we employed both the Edmonton Frail Scale (EFS), as a practical tool to capture the multidimensionality of frailty, and the frailty phenotype, as a measure of physical function. We found that D-serine and D-/Total serine ratio were independent predictors of EFS but not of physical frailty. Furthermore, higher levels of glycine, glycine/L-serine and D-/Total serine were associated with worse cognition and depressive symptoms in the frail group. These findings suggest that changes in peripheral glycine and serine enantiomers homeostasis may represent a novel biochemical correlate of frailty.

Quantifying myelin density in the feline auditory cortex.

The cerebral cortex comprises many distinct regions that differ in structure, function, and patterns of connectivity. Current approaches to parcellating these regions often take advantage of functional neuroimaging approaches that can identify regions involved in a particular process with reasonable spatial resolution. However, neuroanatomical biomarkers are also very useful in identifying distinct cortical regions either in addition to, or in place of functional measures. For example, differences in myelin density are thought to relate to functional differences between regions, are sensitive to individual patterns of experience, and have been shown to vary across functional hierarchies in a predictable manner. Accordingly, the current study provides quantitative stereological estimates of myelin density for each of the 13 regions that make up the feline auditory cortex. We demonstrate that significant differences can be observed between auditory cortical regions, with the highest myelin density observed in the regions that comprise the auditory core (i.e., the primary auditory cortex and anterior auditory field). Moreover, our myeloarchitectonic map suggests that myelin density varies in a hierarchical fashion that conforms to the traditional model of spatial organization in auditory cortex. Taken together, these results establish myelin as a useful biomarker for parcellating auditory cortical regions, and provide detailed estimates against which other, less invasive methods of quantifying cortical myelination may be compared.

Pre-clinical Models for Geriatric Pharmacotherapy.

With ageing of the population worldwide and discovery of new medications for prevention and management of age-related conditions, there is increasing use of medications by older adults. There are international efforts to increase the representativeness of participants in clinical trials to match the intended real-world users of the medications across a range of characteristics including age, multimorbidity, polypharmacy and frailty. Currently, much of the data on medication-related harm in older adults are from pharmacovigilance studies. New methods in pre-clinical models have allowed for measurement of exposures (such as chronic exposure, polypharmacy and deprescribing) and outcomes (such as health span functional measures and frailty) that are highly relevant to geriatric pharmacotherapy. Here we describe opportunities for design and implementation of pre-clinical models that can better predict drug effects in geriatric patients. This could improve the translation of new drugs from bench to bedside and improve outcomes of pharmacotherapy in older adults.

The cutoff values of functional independence measure scores for predicting discharge destination in the early stroke phase.

This study aimed to determine cutoff values of functional independence measure (FIM) scores to predict the discharge destinations of patients with acute stroke. The sample included 318 patients with acute stroke (mean age, 72.0 years; women, 39%). The discharge destination was categorized into three groups: home, postacute rehabilitation (hospital with convalescent rehabilitation wards), and postacute care (institution without convalescent rehabilitation wards). We assessed FIM after lifting bed restriction. Multinomial logistic regression analyses were used to estimate odds ratios (OR) and 95% confidence intervals (CI) of the FIM scores for predicting discharge destinations, with postacute rehabilitation as a reference. Cutoff values of motor and cognitive FIM scores for distinguishing home from postacute rehabilitation and postacute care from postacute rehabilitation were determined using receiver operating characteristic curves. The proportion of home, postacute rehabilitation, and postacute care were 34.6%, 41.8%, and 23.6%, respectively. After adjustments for clinical variables, the ORs (95% CIs) for motor and cognitive FIM scores for home versus postacute rehabilitation were 1.08 (1.04-1.11) and 1.05 (0.98-1.12). Furthermore, those for postacute care versus postacute rehabilitation were 1.01 (0.98-1.04) and 0.92 (0.87-0.98). The cutoff values of the motor and cognitive FIM scores for distinguishing home from postacute rehabilitation were 37.5 (sensitivity: 0.92; specificity: 0.64) and 23.5 (sensitivity: 0.78; specificity: 0.67). Furthermore, those for distinguishing postacute care from postacute rehabilitation were 15.5 (sensitivity, 0.81; specificity, 0.51) and 12.5 (sensitivity, 0.74; specificity, 0.64). The identified cutoff values may serve as early indicators for predicting discharge destinations from acute stroke care.

“Negative affectivity distorts thinking”: a multilevel analysis of criminogenic thinking among Pakistani incarcerated offenders

ABSTRACT The primary aim of the study was to assess the role of negative affectivity, a dynamic factor, in predicting criminogenic thinking styles after considering the roles of stable personal factors, individual and family history of crime, and cognitive functioning. A secondary objective was to assess whether first-time vs. repeat Pakistani incarcerated offenders differ on criminogenic cognitions. A sample of 205 offenders incarcerated in Pakistani prisons completed self-report measures of negative affectivity, cognitive functioning, and criminogenic cognitions. Hierarchical multiple regression analyses were calculated to test the study hypotheses. Findings revealed that negative affectivity factors, particularly fear, were more important for understanding criminogenic cognitive patterns as they explained a significantly larger variance over and above the individual variables, history factors, and cognitive functioning in criminogenic thinking. Further findings showed that repeat offenders scored consistently higher on criminogenic cognitions compared to first-time offenders. The findings highlight the importance of developing prevention programs incorporating cognitive behavior therapeutic strategies targeting negative affectivity and criminogenic cognitions among incarcerated offenders.

Health outcomes and healthcare utilization associated with four undiagnosed chronic conditions: evidence from nationally representative survey data in Sri Lanka

BackgroundLow awareness of chronic conditions raises the risk of poorer health outcomes and may result in healthcare utilization and spending in response to symptoms of undiagnosed conditions. Little evidence exists, particularly from lower-middle-income countries, on the health and healthcare use of undiagnosed people with an indication of a condition. This study aimed to compare health (physical, mental, and health-related quality of life (HRQoL)) and healthcare (inpatient and outpatient visits and out-of-pocket (OOP) medical spending) outcomes of undiagnosed Sri Lankans with an indication of coronary heart disease (CHD), hypertension, diabetes, and depression with the outcomes of their compatriots who were diagnosed or had no indication of these conditions.MethodsThis study used a nationally representative survey of Sri Lankan adults to identify people with an indication of CHD, hypertension, diabetes, or depression, and ascertain if they were diagnosed. Outcomes were self-reported measures of physical and mental functioning (12-Item Short Form Survey (SF-12)), HRQoL (EQ-5D-5L), inpatient and outpatient visits, and OOP spending. For each condition, we estimated the mean of each outcome for respondents with (a) no indication, (b) an indication without diagnosis, and (c) a diagnosis. We adjusted the group differences in these means for socio-demographic covariates using ordinary least squares (OLS) regression for physical and mental function, Tobit regression for HRQoL, and a generalized linear model (GLM) for healthcare visits and OOP spending.ResultsAn indication of each of CHD and depression, which are typically symptomatic, was associated with a lower adjusted mean of physical (CHD -2.65, 95% CI -3.66, -1.63; depression -5.78, 95% CI -6.91, -4.64) and mental functioning (CHD -2.25, 95% CI -3.38, -1.12; depression -6.70, 95% CI -7.97, -5.43) and, for CHD, more annual outpatient visits (2.13, 95% CI 0.81, 3.44) compared with no indication of the respective condition. There were no such differences for indications of hypertension and diabetes, which are often asymptomatic.ConclusionsLiving with undiagnosed CHD and depression was associated with worse health and, for CHD, greater utilization of healthcare. Diagnosis and management of these symptomatic conditions can potentially improve health partly through substitution of effective healthcare for that which primarily responds to symptoms.

An Algorithm, Integrating a Short Form of the Functional Autonomy Measurement System, to Predict Discharge Destination After Acute Care Post-Stroke

Purpose: This study develops a short form of the Functional Autonomy Measurement System (SMAF), the SF-SMAF, for measuring functional capacity in patients undergoing acute care post-stroke, identifies predictors of the discharge destination chosen by the care team, and derives an algorithm that integrates the SF-SMAF and other predictors to guide discharge planning. Method: This multisite prospective cohort study involved 200 patients assessed with the SMAF within 8 days post-stroke. Sociodemographic and clinical data were extracted from patients’ medical records. We performed linear regressions to identify subsets of SMAF items that closely approximate the SMAF total score and asked a panel of experts to make the final selection. We used logistic regression to develop an algorithm that predicts discharge destinations using the SF-SMAF and other predictors. Results: The SF-SMAF includes four items: “washing”, “walking inside”, “judgment”, and “budgeting”. It is highly correlated with the SMAF ( R2 = 0.94) and, alone, predicts 71% of discharge destinations. Adding obstacles to returning home, support required from caregivers, and the ability to communicate, raises the prediction of the proposed algorithm to 82%. Conclusions: The SF-SMAF results closely approximate those of the SMAF in the first week post-stroke. Following further validation, the proposed algorithm could guide clinicians in using the SF-SMAF for discharge planning.

BOLD fMRI responses to amplitude modulated sounds across age in adult listeners

Abstract Age-related alterations in the auditory system have been suggested to affect the processing of temporal envelope amplitude modulations (AM) at different levels of the auditory hierarchy, yet few studies have used functional magnetic resonance imaging (fMRI) to study this noninvasively in humans with high spatial resolution. In this study, we utilized sparse-sampling fMRI at 3 Tesla (3T) to investigate regional blood oxygenation level-dependent (BOLD) responses to AM noise stimuli in 65 individuals ranging in age from 19 to 77 years. We contrasted BOLD responses to AM noise stimuli modulated at 4 Hz or 80 Hz with responses to unmodulated stimuli. This allowed us to derive functional measures of regional neural sensitivity to the imposed AM. Compared to unmodulated noise, slowly varying 4 Hz AM noise stimuli elicited significantly greater BOLD responses in the left and right auditory cortex along the Heschl’s gyrus (HG). BOLD responses to the 80 Hz AM stimuli were significantly greater than responses to unmodulated stimuli in putatively primary auditory cortical regions in the lateral HG. BOLD responses to 4 Hz AM stimuli were significantly greater in magnitude than responses to 80 Hz AM stimuli in auditory cortical regions. We find no discernible effects of age on the functional recruitment of the auditory cortex by AM stimuli. While the results affirm the involvement of the auditory cortex in processing temporal envelope rate information, they provide no support for age-related effects on these measures. We discuss potential caveats in assessing age-related changes in responses to AM stimuli in the auditory pathway.

Natural History of Visual Acuity and Microperimetry-Based Functional Outcome Measures of the Macula in Patients with Geographic Atrophy: A Retrospective Chart Review Study in Germany

Background/Objectives: Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) leading to the progressive and irreversible loss of visual function. Characteristics of GA include atrophic lesions resulting from the loss of photoreceptors, retinal pigment epithelium, and choriocapillaris. During GA progression, atrophic lesions typically advance from the macular periphery to the center, affecting foveal light sensitivity and visual acuity. This study analyzed changes in light sensitivity and visual acuity during the natural course of GA progression using the topographic analysis of structural and functional changes based on Early Treatment Diabetic Retinopathy Study (ETDRS) charts, multimodal imaging, and microperimetry assessment. Methods: Medical chart data of GA patients between 2014 and 2022 from the Internationale Innovative Ophthalmochirurgie GbR (I.I.O.) research center (Düsseldorf, Germany) were retrospectively analyzed. All patient eyes fulfilling the phase 3 OAKS study inclusion criteria were included and followed up for 60 months. The imputation of missing measurements and dropouts was performed by linear mixed models. Results: A total of 20 GA eyes from 13 GA patients were included in the study. At the index, 53.8% of patients had bilateral GA, with 70.0% of the eyes showing multifocal GA and 30.0% subfoveal encroachment (SFE). A total of 35.0% of the eyes had 2–5, and 15.0% over 20, areas of atrophy. Over time, the GA lesion size increased from 6.4 mm2 to 11.8 mm2 (1.08 mm2/year). After an average observation time of 2.9 years, 78.6% of the initially unaffected study eyes developed SFE. The percentage of study eyes without visual impairment decreased from 55.0% to 30.0%, with mean normal-luminance best-corrected visual acuity (NL-BCVA) reducing from 63.7 to 55.7 ETDRS letters. The share of absolute scotoma points in microperimetry assessment increased from 15.7% to 43.5% while overall average macular sensitivity declined from 15.7 dB to 7.4 dB. Conclusions: The substantial deterioration of macular outcomes and visual function was comprehensively detected. The results were a documentation of structural and functional aspects of the natural progression of GA for a 60-month follow-up, providing a typical outline for AMD patients with GA.

The Relationship Between Postural Torticollis Abnormalities and Plagiocephaly on the Early Motor Development Milestones of Lying and Rolling Activities in Infants: A Retrospective Study

ABSTRACT The study examined how neck muscle imbalance and plagiocephaly affect the lying and rolling activities in 118 infants aged 4 to 6 months with postural torticollis. Outcome measures included age, sex, cervical movement, and plagiocephaly severity. Neck muscle function was assessed with the Muscle Function Scale (MFS), and infant motor abilities in lying and rolling were evaluated through the corresponding dimensions of the Gross Motor Function Measure (GMFM). Multiple regression analysis showed that a better MFS score of the affected neck was significantly associated with improved lying and rolling activities in the GMFM (p < .01), and importantly, the interaction between the plagiocephaly and the MFS scores of the affected neck muscle in these activities was found to be significant (p < .05). These results highlight the need for early intervention in infants with torticollis to address muscle imbalance and plagiocephaly, crucial for early motor development (KCT0008367).

The effect of post-match fatigue on physical performance in adolescent soccer players.

Soccer involves many physically challenging actions and engaging in such activities can induce a decline in performance due to physical fatigue which predisposes players to develop injuries. The present study aimed to examine the impact of post-match fatigue on functional performance and Inter-Limb Asymmetry Index (LSI) in adolescent soccer players. Thirty-eight adolescent male soccer players (15-18 years) completed a battery of functional performance measures (Rate of Perceived Exertion (RPE) scale, 10 m sprint, agility T-test, and Single leg hop for distance (SLHD) test). The data collection started prior to a soccer match and consisted of two testing sessions; two hours before the match, while the subsequent testing session was performed within two hours immediately following the match. The study results revealed a significant effect of post-match fatigue on change of direction abilities and SLHD (moderate effect size). However, no significant differences were observed in the 10 m sprint test and LSI (P>0.05). Functional performance measures such as agility test and SLHD test can detect physical ability changes due to post-match fatigue in adolescent soccer players. The study findings offer insightful and practical information on the importance of employing field-based functional performance measures in monitoring players' recovery following a game.

Enhancing team communication to improve implementation of a supervised walking program for hospitalized veterans: Evidence from a multi-site trial in the Veterans Health Administration.

The timely translation of evidence-based programs into real-world clinical settings is a persistent challenge due to complexities related to organizational context and team function, particularly in inpatient settings. Strategies are needed to promote quality improvement efforts and implementation of new clinical programs. This study examines the role of CONNECT, a complexity science-based implementation intervention to promote team readiness, for enhancing implementation of the 'Assisted Early Mobility for Hospitalized Older Veterans' program (STRIDE), an inpatient, supervised walking program. We conducted a stepped-wedge cluster randomized trial using a convergent mixed-methods design. Within each randomly assigned stepped-wedge sequence, Veterans Affairs Medical Centers (VAMCs) were randomized to receive standardized implementation support only or additional training via the CONNECT intervention. Data for the study were obtained from hospital administrative and electronic health records, surveys, and semi-structured interviews with clinicians before and after implementation of STRIDE. Eight U.S. VAMCs. Three hundred fifty-three survey participants before STRIDE implementation and 294 surveys after STRIDE implementation. Ninety-two interview participants. CONNECT, a complexity-science-based intervention to improve team function. The implementation outcomes included STRIDE reach and fidelity. Secondary outcomes included validated measures of team function (i.e., team communication, coordination, role clarity). At four VAMCs randomized to CONNECT, reach was higher (mean 12.4% vs. 3.8%), and fidelity was similar to four non-CONNECT VAMCs. VAMC STRIDE delivery teams receiving CONNECT reported improvements in team function domains, similar to non-CONNECT VAMCs. Qualitative findings highlight CONNECT's impact and the influence of team characteristics and contextual factors, including team cohesion, leadership support, and role clarity, on reach and fidelity. CONNECT may promote greater reach of STRIDE, but improvement in team function among CONNECT VAMCs was similar to improvement among non-CONNECT VAMCs. Qualitative findings suggest that CONNECT may improve team function and implementation outcomes but may not be sufficient to overcome structural barriers related to implementation capacity.

Assessment of objective visual function following idebenone administration in patients with leber hereditary optic neuropathy.

To objectively assess visual function in Leber's Hereditary Optic Neuropathy (LHON) patients; this study evaluated pre- and post-idebenone treatment changes in primary visual cortical (V1) responses using functional magnetic resonance imaging (fMRI), given the challenges in subjective testing due to central retinal ganglion cell damage. A descriptive study involving four confirmed LHON patients. Four patients received 900 mg/day of oral idebenone for 24 weeks. Baseline and post-treatment visual acuity, visual fields, and BOLD fMRI responses while passively viewed drifting contrast pattern visual stimuli were compared with self-reported symptoms. Post-idebenone, one patient showed positive trends across subjective tests, reported symptoms, and fMRI. Two patients had stable symptoms and fMRI responses; one improved on subjective tests, and another worsened slightly. Another patient improved in visual field tests despite worsening symptoms and fMRI trends. fMRI may offer a valuable objective measure of visual functions in LHON and appears to be more relevant in assessing symptoms. Further research with more participants is needed to ascertain fMRI's role in developing objective visual assessments and treatment evaluation.

Saturation genome editing maps the functional spectrum of pathogenic VHL alleles.

To maximize the impact of precision medicine approaches, it is critical to identify genetic variants underlying disease and to accurately quantify their functional effects. A gene exemplifying the challenge of variant interpretation is the von Hippel-Lindautumor suppressor (VHL). VHL encodes an E3 ubiquitin ligase that regulates the cellular response to hypoxia. Germline pathogenic variants in VHL predispose patients to tumors including clear cell renal cell carcinoma (ccRCC) and pheochromocytoma, and somatic VHL mutations are frequently observed in sporadic renal cancer. Here we optimize and apply saturation genome editing to assay nearly all possible single-nucleotide variants (SNVs) across VHL's coding sequence. To delineate mechanisms, we quantify mRNA dosage effects and compare functional effects in isogenic cell lines. Function scores for 2,268 VHL SNVs identify a core set of pathogenic alleles driving ccRCC with perfect accuracy, inform differential risk across tumor types and reveal new mechanisms by which variants impact function. These results have immediate utility for classifying VHL variants encountered clinically and illustrate how precise functional measurements can resolve pleiotropic and dosage-dependent genotype-phenotype relationships across complete genes.

Monitoring handgrip strength to motivate lifestyle choices for patients with diabetes type 2 – a pragmatic randomised controlled trial

Physical strength can be an important parameter to monitor for patients with diabetes mellitus type 2 (T2DM) to promote healthy lifestyle choices. Functional measurements can contribute to healthcare advice and possibly motivate more active lifestyles. The aim of the study was to investigate whether adding measurement and feedback concerning handgrip strength (HGS) to the parameters measured for patients with T2DM at annual check-ups leads to change in physical activity (PA) level, HGS, HbA1c or waist circumference. Methods Measurement of HGS with Jamar dynamometers was added to annual check-ups for patients with T2DM by diabetes nurses in primary care with feedback about normal values for age and sex in the intervention group. The control group had standard check-ups. Change in self-reported PA level was measured with questionnaires. Results Seven clinics and 334 patients participated. The intervention led to similar effects on PA in both groups. Patients with T2DM had comparable HGS to the general public. Regression analyses showed statistically significantly higher HGS in the intervention group than in the control group at follow-up and no improvement in PA, HbA1c, or waist circumference. Increased HGS was found for older people, men, and people with normal-to-high inclusion HGS, while patients with low inclusion HGS reduced their strength levels. Conclusions Measuring HGS and giving feedback to patients with T2DM can lead to increased HGS but does not seem to affect general PA level, HbA1c, or waist circumference. People over 65 years, men, and people with normal-to-high HGS were influenced positively by the intervention. Patients with low HGS may need personalised support to increase physical activity and improve function. ClinicalTrials registration: NCT03693521

Novel measures of cognition and function for the AD spectrum in the Novel Measures for Alzheimer's Disease Prevention Trials (NoMAD) project: Psychometric properties, convergent validation, and contrasts with established measures.

This study derived composite scores for two novel cognitive measures, the No Practice Effect (NPE) battery and the Miami Computerized Functional Skills Assessment and Training system for use in early-stage Alzheimer's disease (AD) clinical trials. Their psychometric properties and associations with AD risk markers were compared to those of well-established measures. For 291 older adults with healthy cognition or early mild cognitive impairment, Exploratory factor analyses were used to identify the factor structure of the NPE. Factor and total scores were examined for their psychometric properties and associations with AD risk biomarkers. Composite scores from the novel cognitive and functional measures demonstrated better psychometric properties (distribution and test-retest reliability) and stronger associations with AD-related demographic, genetic, and brain risk markers than well-established measures, DISCUSSION: These novel measures have potential for use as primary cognitive and functional outcomes in early-stage AD clinical trials. Well-established cognitive tests may not accurately detect subtle cognitive changes. No Practice Effect (NPE) and Computerized Functional Skills Assessment and Training are novel measures designed to have improved psychometric properties. NPE had Executive Function, Cognitive Control/Speed, and Episodic Memory domains. Novel measures had better psychometric properties compared to established measures. Significant associations with Alzheimer's disease biomarkers were found with novel measures.

Lesion characteristics are associated with bowel, bladder, and overall independence following cervical spinal cord injury

Context/Objective There is a growing global interest in quantifying spinal cord lesions and spared neural tissue using magnetic resonance imaging (MRI) in individuals with spinal cord injury (SCI). The primary objective of this study was to assess the relationships between spinal cord lesion characteristics assessed on MRI and bowel, bladder, and overall independence following SCI. Design Retrospective, exploratory study. Participants 93 individuals with cervical SCI who were enrolled in a local United States Model Systems SCI database from 2010 to 2017. Methods Clinical and MRI data were obtained for potential participants, and MRIs of eligible participants were analyzed. Explanatory variables, captured on MRIs, included intramedullary lesion length (IMLL), midsagittal ventral tissue bridge width (VTBW), midsagittal dorsal tissue bridge width (DTBW), and axial damage ratio (ADR). Outcome Measures Bowel and bladder management scale of the Functional Independence Measure (FIM) and FIM total motor score. Results When accounting for all four variables, only ADR was significantly associated with bowel independence (OR = 0.970, 95% CI: 0.942–0.997, P = 0.030), and both ADR and IMLL were strongly associated with bladder independence (OR = 0.967, 95% CI: 0.936–0.999, P = 0.046 and OR = 0.948, 95% CI: 0.919–0.978, P = 0.0007, respectively). 32% of the variation in overall independence scores were explained by all four predictive variables, but only ADR was significantly associated with overall independence after accounting for all other predictive variables (β = −0.469, 95% CI: −0.719, −0.218, P = 0.0004). Conclusions Our results suggest that the MRI-measured extent of spinal cord lesion may be predictive of bowel, bladder, and overall independence following cervical SCI.