Measures Of Function Research Articles

Modeling seizure networks in neuron-glia cultures using microelectrode arrays.

Epilepsy is a common neurological disorder, affecting over 65 million people worldwide. Unfortunately, despite resective surgery, over 30 of patients with drug-resistant epilepsy continue to experience seizures. Retrospective studies considering connectivity using intracranial electrocorticography (ECoG) obtained during neuromonitoring have shown that treatment failure is likely driven by failure to consider critical components of the seizure network, an idea first formally introduced in 2002. However, current studies only capture snapshots in time, precluding the ability to consider seizure network development. Over the past few years, multiwell microelectrode arrays have been increasingly used to study neuronal networks in vitro. As such, we sought to develop a novel in vitro MEA seizure model to allow for study of seizure networks. Specifically, we used 4-aminopyridine (4-AP) to capture hyperexcitable activity, and then show increased network changes after 2days of chronic treatment. We characterize network changes using functional connectivity measures and a novel technique using dimensionality reduction. We find that 4-AP successfully captures persistently elevated mean firing rate and significant changes in underlying connectivity patterns. We believe this affords a robust in vitro seizure model from which longitudinal network changes can be studied, laying groundwork for future studies exploring seizure network development.

Quantitative muscle MRI in sporadic inclusion body myositis (sIBM): A prospective cohort study.

Sporadic inclusion body myositis (sIBM) is the predominant idiopathic inflammatory myopathy (IIM) in older people. Limitations of classical clinical assessments have been discussed as possible explanations for failed clinical trials, underlining the need for more sensitive outcome measures. Quantitative muscle MRI (qMRI) is a promising candidate for evaluating and monitoring sIBM. Longitudinal assessment of qMRI in sIBM patients. We evaluated fifteen lower extremity muscles of 12 sIBM patients (5 females, mean age 69.6, BMI 27.8) and 12 healthy age- and gender-matched controls. Seven patients and matched controls underwent a follow-up evaluation after one year. Clinical assessment included testing for muscle strength with Quick Motor Function Measure (QMFM), IBM functional rating scale (IBM-FRS), and gait analysis (6-minute walking distance). 3T-MRI scans of the lower extremities were performed, including a Dixon-based sequence, T2 mapping and Diffusion Tensor Imaging. The qMRI-values fat-fraction (FF), water T2 relaxation time (wT2), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1), and radial diffusivity (RD) were analysed. Compared to healthy controls, significant differences for all qMRI parameters averaged over all muscles were found in sIBM using a MANOVA (p < 0.001). In low-fat muscles (FF < 10%), a significant increase of wT2 and FA with an accompanying decrease of MD, λ1, and RD was observed (p≤0.020). The highest correlation with clinical assessments was found for wT2 values in thigh muscles (r≤-0.634). Significant changes of FF (+3.0%), wT2 (+0.6 ms), MD (-0.04 10-3mm2/s), λ1 (-0.05 10-3mm2/s), and RD (-0.03 10-3mm2/s) were observed in the longitudinal evaluation of sIBM patients (p≤0.001). FA showed no significant change (p = 0.242). qMRI metrics correlate with clinical findings and can reflect different ongoing pathophysiological mechanisms. While wT2 is an emerging marker of disease activity, the role of diffusion metrics, possibly reflecting changes in fibre size and intracellular deposits, remains subject to further investigations.

Generalisability of the Barthel Index and the Functional Independence Measure: robustness of disability measures to Differential Item Functioning

Purpose Differential Item Functioning (DIF), an item malfunctioning, causes Differential Test Functioning (DTF), thus biasing questionnaire measures. The current study evaluates the relationship between DIF and DTF for the Barthel Index and the Functional Independence Measure, likely the most used disability measures. The aim is to understand under which conditions DIF can be ignored as its DTF is negligible. Methods A simulation study was run. Disability measures were obtained for the Barthel Index and FIM motor domain using Rasch analysis with previously published item calibrations. Several DIF scenarios have been assessed. DTF was tolerable if ≤0.50 logits. Results Simulations showed that the larger the DIF, the larger the DTF and that, keeping the overall DIF constant, the total number of items with DIF does not affect DTF. DIF of the items with the lowest or highest calibrations is the most dangerous. The DIF of central items should be so massive to matter in DTF terms that it is unlikely to happen in practice. The FIM robustness to DIF is better than that of the Barthel Index. Conclusions The FIM and the Barthel Index show remarkable robustness to DIF. Thanks to this feature, sample invariant, generalisable disability measures are available.

STNMDA: A Novel Model for Predicting Potential Microbe-Drug Associations with Structure-Aware Transformer

Introduction: Microbes are intimately involved in the physiological and pathological processes of numerous diseases. There is a critical need for new drugs to combat microbe-induced diseases in clinical settings. Predicting potential microbe-drug associations is, therefore, essential for both disease treatment and novel drug discovery. However, it is costly and time-consuming to verify these relationships through traditional wet lab approaches. Methods: We proposed an efficient computational model, STNMDA, that integrated a StructureAware Transformer (SAT) with a Deep Neural Network (DNN) classifier to infer latent microbedrug associations. The STNMDA began with a “random walk with a restart” approach to construct a heterogeneous network using Gaussian kernel similarity and functional similarity measures for microorganisms and drugs. This heterogeneous network was then fed into the SAT to extract attribute features and graph structures for each drug and microbe node. Finally, the DNN classifier calculated the probability of associations between microbes and drugs. Results: Extensive experimental results showed that STNMDA surpassed existing state-of-the-art models in performance on the MDAD and aBiofilm databases. In addition, the feasibility of STNMDA in confirming associations between microbes and drugs was demonstrated through case validations. Conclusion: Hence, STNMDA showed promise as a valuable tool for future prediction of microbedrug associations.

Impact of Aficamten on Echocardiographic Cardiac Structure and Function in Symptomatic Obstructive Hypertrophic Cardiomyopathy

BackgroundAficamten, a next-in-class cardiac myosin inhibitor, improved peak oxygen uptake (pVO2) and lowered resting and Valsalva left ventricular outflow (LVOT) gradients in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) in SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM), a phase 3, multicenter, randomized, double-blinded, placebo-controlled study. ObjectivesThe authors sought to evaluate the effect of aficamten on echocardiographic measures of cardiac structure and function in SEQUOIA-HCM. MethodsSerial echocardiograms were performed over 28 weeks in patients randomized to receive placebo or aficamten in up to 4 individually titrated escalating doses (5-20 mg daily) over 24 weeks based on Valsalva LVOT gradients and left ventricular ejection fraction (LVEF). ResultsAmong 282 patients (mean age 59 ± 13 years; 41% female, 79% White, 19% Asian), mean LVEF was 75% ± 6% with resting and Valsalva LVOT gradients of 55 ± 30 mm Hg and 83 ± 32 mm Hg, respectively. Over 24 weeks, aficamten significantly lowered resting and Valsalva LVOT gradients, and improved left atrial volume index, lateral and septal eʹ velocities, and lateral and septal E/eʹ (all P ≤ 0.001). LV end-systolic volume increased and wall thickness decreased (all P ≤ 0.003). Aficamten resulted in a mild reversible decrease in LVEF (−4.8% [95% CI: −6.4% to −3.3%]; P < 0.001) and absolute LV global circumferential strain (−3.7% [95% CI: 1.8%-5.6%]; P < 0.0010), whereas LV global longitudinal strain was unchanged. Several measures, including LVEF, LVOT gradients, and E/eʹ returned to baseline following washout. Among those treated with aficamten, improved pVO2 and reduction in N-terminal pro–B-type natriuretic peptide (NT-proBNP) were associated with improvement in lateral eʹ velocity and septal and lateral E/eʹ (all P < 0.03), whereas improvement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores (KCCQ-CSS) was associated with a decrease in both LVOT gradients (all P < 0.001). ConclusionsCompared with placebo, patients receiving aficamten demonstrated significant improvement in LVOT gradients and measures of LV diastolic function, and several of these measures were associated with improvements in pVO2, KCCQ-CSS, and NT-proBNP. A modest decrease in LVEF occurred yet remained within normal range. These findings suggest aficamten improved multiple structural and physiological parameters in oHCM without significant adverse changes in LV systolic function. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM [SEQUOIA-HCM]; NCT05186818)

Pain Interference in Juvenile Idiopathic Arthritis.

Despite treatment advances, pain remains a serious problem for many children with juvenile idiopathic arthritis (JIA). To better understand pain in children with JIA and identify potentially modifiable factors, this study evaluated Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Pain Interference (PI) and its relationships with other pain measures and demographic, clinical, psychosocial, and functional variables. This cross-sectional, observational, multicenter study used descriptive statistics and a mix of bivariate and multivariable analyses to describe PI and characterize relationships with other measures and variables. Among 355 children with JIA, 27% reported moderate or severe PI and 13.3% reported daily pain. PI correlated with other pain measures. Increasing age, decreasing disease duration, and increasing number of active joints, as well as presence of active disease, steroid treatment, and biologic treatment, were associated with greater PI. All PROMIS psychosocial and functional measures were associated with PI in the expected direction except for PROMIS Pediatric Physical Activity, which showed no association. In multivariable analyses, only PROMIS Fatigue, PROMIS Mobility, and the exploratory interaction of PROMIS Anxiety and disease-modifying antirheumatic drug treatment were significant. Moderate and severe PI was prevalent in this sample of children with JIA. PI increased with age and indicators of disease activity, but was more strongly associated with increasing fatigue and decreasing mobility. Findings support the use of PI as a short, easily administered multidimensional pain measure as part of routine clinical care. Fatigue, mobility, and disease activity should be assessed further when PI is high.

Longitudinal prediction of psychosocial functioning outcomes: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Section-II personality disorders versus alternative model personality dysfunction and traits.

We aimed to determine and compare the longitudinal predictive power of Diagnostic and Statistical Manual of Mental Disorders, fifth edition's (DSM-5) two models of personality disorder (PD) for multiple clinically relevant outcomes. A sample of 600 community-dwelling adults-half recruited by calling randomly selected phone numbers and screening-in for high-risk for personality pathology and half in treatment for mental health problems-completed an extensive battery of self-report and interview measures of personality pathology, clinical symptoms, and psychosocial functioning. Of these, 503 returned for retesting on the same measures an average of 8 months later. We used Time 1 interview data to assess DSM-5 personality pathology, both the Section-II PDs and the alternative (DSM-5) model of personality disorder's (AMPD) Criterion A (impairment) and Criterion B (adaptive-to-maladaptive-range trait domains and facets). We used these measures to predict 20 Time 2 functioning outcomes. Both PD models significantly predicted functioning-outcome variance, albeit modestly-averaging 12.6% and 17.9% (Section-II diagnoses and criterion counts, respectively) and 15.2% and 23.2% (AMPD domains and facets, respectively). Each model significantly augmented the other in hierarchical regressions, but the AMPD domains (6.30%) and facets (8.62%) predicted more incremental variance than the Section-II diagnoses (3.74%) and criterion counts (3.31%), respectively. Borderline PD accounted for just over half of Section II's predictive power, whereas the AMPD's predictive power was more evenly distributed across components. We note the predictive advantages of dimensional models and articulate the theoretical and clinical advantages of the AMPD's separation of personality functioning impairment from how this is manifested in personality traits. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Correlation between Respiratory Symptoms Questionnaire and Pulmonary Function Test in Chronic Obstructive Lung Disease Patients: A Tertiary Care Hospital Study

Abstract Objective: This study aimed to investigate the correlation between respiratory symptoms assessed by the Respiratory Symptoms Questionnaire (RSQ) and pulmonary function test (PFT) results in patients diagnosed with chronic obstructive pulmonary disease (COPD) at a tertiary care hospital. Methods: This analytical, cross-sectional study was conducted at Sree Balaji Medical College and Hospital, Chennai, involving 130 COPD patients presenting with symptoms of breathlessness, chronic cough, and wheeze. Data collection instruments used were: (1) RSQ: The RSQ was utilized to assess respiratory symptoms, including breathlessness, cough, and wheeze, (2) PFT: PFT assessments, including spirometry, were performed to measure lung function impairment objectively. Participants completed the RSQ under supervision, followed by PFT assessments conducted by trained respiratory technologists using standardized procedures. Results: Descriptive statistics were computed for demographic variables and questionnaire scores. Pearson correlation analysis was employed to assess the association between respiratory symptoms measured by RSQ and PFT parameters. The Chi-square analysis determined the overall association between symptom scores and PFT results across the COPD severity groups. Significant correlations were observed between severe COPD and St. George’s Respiratory Questionnaire, moderate COPD and Clinical COPD Questionnaire, and moderate-to-severe COPD and COPD Assessment Test (P &lt; 0.05). Nonsignificant correlations were found between mild COPD and symptom scores (P &gt; 0.05). The Chi-square analysis confirmed a strong association between respiratory symptoms and PFT results (P = 0.04). Conclusion: This study highlights the importance of comprehensive symptom assessment alongside the objective measures of lung function in COPD management. Integrating tools such as RSQ with PFTs enables clinicians to obtain a holistic understanding of patients’ disease status and tailor treatment strategies accordingly.

Episodes of acute methotrexate-related neurotoxicity linked to compromised long-term neurocognitive function.

Methotrexate is a critical component of curative chemotherapy for pediatric acute lymphoblastic leukemia (ALL), but is associated with neurotoxicity. Information on long-term outcomes following an acute neurotoxic event is limited. Therefore, this report compares neurocognitive performance more than 12months post diagnosis (mean=4years) between ALL patients with (n=25) and without (n=146) a history of acute neurotoxicity. Compared to children with no documented on-treatment neurotoxic event, children who experienced a neurotoxic event during treatment exhibited poorer performance on measures of fine motor function (p=.02) and attention (p=.02). Children with ALL who experience acute neurotoxicity may be candidates for early neuropsychological screening and intervention.

Effects of a 6-Week Treadmill Training With and Without Virtual Reality on Frailty in People With Multiple Sclerosis

ObjectiveTo examine the effects of a cognitive-motor rehabilitation program consisting of treadmill training (TT) augmented by virtual reality (TT+VR) on frailty in people with multiple sclerosis (pwMS). DesignSecondary analysis from a multicenter randomized controlled trial investigating the effects of TT+VR, compared with TT only, on measures of mobility and cognitive function in pwMS. SettingFour university research laboratories in 3 countries. ParticipantsA total of 124 pwMS were randomized into the parent trial. Here, we studied a subset of n = 83 participants (mean age, 49.4±9.3y; 73.5% female; expanded disability status scale range, 2.0-6.0), who completed the intervention and had complete preintervention and postintervention frailty data. InterventionsParticipants were randomly allocated to TT+VR (n=44) or TT (n=39). Both groups trained 3 times a week for 6 weeks. Main Outcome MeasuresFrailty was assessed using a 40-item frailty index (FI) through standard validated procedures and represented the primary study outcome. Two exploratory frailty indices were also computed by isolating health-related deficits involving the cognitive (FI-physical) or physical (FI-cognitive) domains from the main FI. The assessments were performed at baseline and after 6 weeks, upon intervention completion. ResultsThe mean FI of study participants at baseline was 0.33±0.13, indicating a moderate average level of frailty. FI scores improved in both TT+VR and TT groups participants (pooled mean ΔFI, 0.024; 95% CI, 0.010-0.038; F=10.49; P=.002; ηp2=0.115), without any group-by-time interaction (F=0.82; P=.367; ηp2=0.010). However, a significant group-by-time interaction was found for pretraining and posttraining changes in FI-cognitive (F=5.74; P=.019; ηp2=0.066), suggesting a greater improvement for TT+VR group participants than for TT group participants. ConclusionsTT with or without virtual reality can reduce frailty levels in pwMS. While both TT and TT+VR had a positive effect on overall frailty, only TT+VR improved cognitive aspects of frailty and may represent an appropriate strategy for counteracting frailty in pwMS.

Serial Changes in Ventricular Strain in Symptomatic Obstructive Hypertrophic Cardiomyopathy Treated With Mavacamten: Insights From the VALOR-HCM Trial.

In severely symptomatic patients with obstructive hypertrophic cardiomyopathy, VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) demonstrated that mavacamten reduces the need for septal reduction therapy with sustained improvement in left ventricular (LV) outflow tract gradients and symptoms. Global longitudinal strain (GLS), a measure of regional myocardial function, is a more sensitive marker of systolic function. In VALOR-HCM, we assessed serial changes in LV and right ventricular (RV) strain. VALOR-HCM included 112 patients with symptomatic obstructive hypertrophic cardiomyopathy (mean, 60 years; 51% male; LV ejection fraction, 68%). Patients assigned to mavacamten at baseline continued the drug for 56 weeks (n=56) and those assigned to placebo (n=52) transitioned to mavacamten from weeks 16 to 56 (40-week exposure). LV-GLS and RV-GLS assessment was performed using a vendor-neutral software. Non-foreshortened apical (4-, 3-, and 2-chamber) views were used to obtain peak LV-GLS. RV focused 4-chamber view was used to calculate RV 4-chamber and free wall strain. A more negative strain value is favorable. At baseline, the mean LV-GLS, RV 4-chamber, and free wall strain values were -14.7%, -22.2%, and -16.8%, respectively (all worse than reported normal means). In the total study sample, LV-GLS significantly improved from baseline to week 56 (P=0.02). Twelve patients had transient reduction in LV ejection fraction (<50%) requiring temporary drug interruption (including 3 permanent discontinuations). The LV-GLS in this subgroup was worse at baseline versus total study population (-11.4%), with no significant worsening from baseline through week 56 (P=0.64). Both free wall and 4-chamber RV-GLS remained unchanged from baseline to week 56 (P=0.62 and P=0.56, respectively). In VALOR-HCM, treatment with mavacamten improved LV-GLS from baseline through week 56 (with no significant worsening of LV-GLS in patients with a reduction in LV ejection fraction ≤50%), suggesting a favorable long-term impact on regional LV systolic function. Additionally, there was no detrimental impact on RV systolic function. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04349072.

Cardiac biomarkers and effects of aficamten in obstructive hypertrophic cardiomyopathy: the SEQUOIA-HCM trial.

The role of biomarker testing in the management of obstructive hypertrophic cardiomyopathy (oHCM) is not well defined. This pre-specified analysis of SEQUOIA-HCM (NCT05186818) sought to define the associations between clinical characteristics and baseline concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI), and to evaluate effect of treatment with aficamten on biomarker concentrations. Cardiac biomarkers were measured at baseline and serially throughout the study. Regression analyses determined predictors of baseline NT-proBNP and hs-cTnI concentrations, and to evaluate whether early changes in these biomarkers relate to later changes in left ventricular outflow tract gradient (LVOT-G), other echocardiographic measures, health status, and functional capacity. Baseline concentration of NT-proBNP was associated with LVOT-G and measures of diastolic function, while hs-cTnI was associated with left ventricular thickness. Within 8 weeks of treatment with aficamten, NT-proBNP was reduced by 79% (95% CI 83%-76%, P < .001) and hs-cTnI by 41% (95% CI 49%-32%, P < .001); both biomarkers reverted to baseline after washout. Reductions in NT-proBNP and hs-cTnI by 24 weeks were strongly associated with a lowering of LVOT-G, improvement in health status, and increased peak oxygen uptake. NT-proBNP reduction strongly correlated with the majority of improvements in exercise capacity. Furthermore, the change in NT-proBNP by Week 2 was associated with the 24-week change in key endpoints. NT-proBNP and hs-cTnI concentrations are associated with key variables in oHCM. Serial measurement of NT-proBNP and hs-cTnI appears to reflect clinical response to aficamten therapy.

Undernutrition, Sarcopenia, Sarcopenic Obesity, and Sarcopenic Undernutrition: A Cross-sectional View on Patients Before Total Joint Arthroplasty.

Diagnostic criteria of malnutrition phenotypes have been recently updated. Uncovering the prevalence of these conditions in patients undergoing hip replacement may be crucial in order to apply the most appropriate diagnostic-therapeutic paths to the right patient at the right time. Sixty patients aged between 60 and 85 undergoing elective hip replacement were recruited. Preoperative measures concerning eating behaviors, anthropometry, physical performance, laboratory parameters, and patient reported measures of pain and function were collected, used to make diagnosis, and explored whether they differed based on malnutrition categorization. Patients undernourished were 18.75%, sarcopenic 13.34%, sarcopenic obesity 4.26%, and 8.88% undernourished and sarcopenic. Well-nourished patients ate more cereals and meat, exhibited lower white blood cells but higher lymphocytes, and reported greater hip-related pain. One in three older patients undergoing elective hip replacement was malnourished. Eating behaviors and leucocytes were the discriminating factors between malnourished and well-nourished. It remains to be established whether malnutrition affects outcome after surgery.

118 Can we reasonably recommend strength training twice weekly for the general adult population aged 18-64 years to secure optimal body functionality?

Abstract Purpose The objective of the study was to conduct a quality assessment of the scientific literature underlying the Danish Health Authorities (DHA) revised recommendations on physical activity (PA), with focus on the new advice on strength training twice a week to secure optimal body functionality in the adult population aged 18-64 years. Methods The study was a scoping review. Reviews conducted by the World Health Organization (WHO), the American and Canadian Health Authorities, and evidence referenced in earlier reports from DHA were included for initial review, as DHA refer to these as base for their PA-guideline revision. Studies included in the reviews were title- and abstract screened to assess whether they investigated PA and/or strength training in a population of adults aged 18-64 years. Studies identified through this screening, were furthermore full text screened, and finally included in a quality assessment, if they investigated a strength training intervention in relation to a measure of body functionality. The quality assessment was inspired by STROBE and the Jadad Scale (for observational studies and RCTs respectively) and extended with an assessment of the study’s research goal compliance (causal or predictive) to evaluate the study’s ability to detect eventual effects of the intervention on body functionality. Results A total of 25 out of 879 studies identified in the reviews were selected for quality assessment. Great variations in quality were identified, and many studies (13 out of 25) did not achieve 2/3 of potential quality points. The studies generally support strength training as an effective intervention on body functionality. However, 15 of the 16 RCTs investigated a study population with functional limitations, e.g. populations with musculoskeletal disorders, and most studies were based on a study population in the higher end of the age spectrum 18-64 years. Conclusions The literature does not clearly support a recommendation on strength training twice weekly for the general adult population to secure optimal body functionality. The formulation of PA-guidelines should be based on evidence that 1) aims to draw causal conclusions on the effect of the recommended intervention and 2) investigates a population comparable to the target audience. Funding None

Prospective Assessment of Outcomes After Femoral Condyle Osteochondral Allograft Transplantation With Concurrent Meniscus Allograft Transplantation.

Osteochondral allograft transplantation (OCAT) and meniscus allograft transplantation (MAT) have each become more commonly implemented for the treatment of young to middle-aged patients with complex knee pathology. Evidence regarding tibiofemoral OCAT in the setting of concurrent MAT is limited. The purpose of this study was to characterize outcomes for femoral condyle OCAT with concurrent MAT (OCAT+MAT) in the ipsilateral compartment of patients after evidence-based shifts in practice. It was hypothesized that OCAT+MAT would be associated with successful outcomes characterized by statistically significant and clinically meaningful improvements in patient-reported outcome measures (PROMs) of knee pain and function in >80% of patients for at least 2 years after transplantation. Case series; Level of evidence, 4. With institutional review board approval and documented informed consent, patients who underwent primary OCAT+MAT between 2016 and 2020 and enrolled in a lifelong registry for prospective collection of outcomes after OCAT were included. Patients with minimum 2-year follow-up data regarding complications, failures, adherence, and PROMs were analyzed. Patients who required OCAT and/or MAT revision or conversion to arthroplasty were defined as experiencing treatment failures. A total of 23 consecutive patients (mean age, 37.1 years; mean body mass index, 28 kg/m2; 14 men) met the inclusion criteria, with a mean follow-up of 51 months (range, 24-86 months). The initial treatment success rate was 78% based on 5 initial treatment failures, and the overall success rate was 83% based on a successful revision OCAT. All failures occurred in the medial compartment. Older patient age (42.2 vs 32.1 years; P = .046) and nonadherence to postoperative restriction and rehabilitation protocols (P = .033; odds ratio, 14) were significant risk factors for treatment failure. All measured PROMs achieved significant improvements (P < .001) and minimum clinically important differences at a minimum of 2 years postoperatively. OCAT+MAT was associated with successful short- to mid-term outcomes in 83% of cases. Evidence-based shifts in practice were implemented before the enrollment of this patient cohort. Older patients and those who were not adherent to postoperative restriction and rehabilitation protocols had a significantly higher risk for treatment failure and subsequent conversion to arthroplasty.

Underweight, dementia, and not being completely independent in bowel management are risk factors for urinary incontinence among older people

Background:Despite the known relationship between frailty and urinary incontinence, the components of frailty that are important in managing urinary incontinence remain unclear. Objectives:This study aimed to investigate physical factors that influenced urinary incontinence. Methods:This prospective observational study included patients admitted to the rehabilitation ward of our hospital from July 2020 to June 2022. Patients’ data were collected during the week before their discharge. Patients who needed diaper changes because of urine contamination were defined as incontinent and others as continent. Univariate and multivariate analyses were used to analyze differences between the two groups by age, sex, medical history, body mass index, serum albumin levels, Mini-Mental State Examination scores, Functional Independence Measure motor items (excluding bladder management), grip strength, gait speed, lower limb muscle strength, posture when seated on the toilet, residual urine volume, medication for lower urinary tract symptoms, and polypharmacy. Results:Of 121 patients, 104 (38 men, 66 women) were included in our analyses. Patients’ median age was 81 years (range 56–101 years). The risk factors for urinary incontinence identified in the multivariate analysis were: history of dementia (odds ratio [OR] 19.80, 95% confidence interval [CI]: 2.31–170.00; p = 0.00646), body mass index < 18.5 kg/m2 (OR 7.09, 95% CI: 1.36–36.90; p = 0.0201), and non-completely independent bowel management (OR 7.19, 95% CI: 1.29–40.16; p = 0.0245). Conclusions:We concluded that dementia, low body mass index, and non-completely independent bowel management are associated with urinary incontinence among older people.

Reduction of pathological retinal neovascularization, vessel obliteration, and artery tortuosity by PEDF protein in an oxygen-induced ischemic retinopathy rat model.

Retinopathy of prematurity (ROP) is a severe retinal disease in premature infants characterized by pathological neovascularization, obliteration of retinal vessels and increased vessel tortuosity. Currently, there are no completely satisfactory treatments for ROP. Pigment epithelium-derived factor (PEDF), a potent inhibitor of angiogenesis, appears late in gestation and its deficiency may be linked to development of ROP. This study investigates the preclinical efficacy of PEDF protein alone or in combination with VEGF antagonists for treating ROP. The safety of PEDF protein in the rat eye was assessed using functional invivo measurements and histology. The efficacy of intravitreal injections (IVI) of various treatments was evaluated in a rat oxygen-induced retinopathy (OIR) model using invivo imaging and flatmount analyses. No functional or histological side-effects were found in rat eyes after intravitreal PEDF protein injection. PEDF protein alone or combined with anti-VEGF drugs significantly reduced pathological neovascularization and vessel obliteration, comparable to the effects of anti-VEGF drugs alone. Regarding arterial tortuosity, treatment with a combination of PEDF, and VEGF antagonist was more effective than treatment with anti-VEGF alone. IVI of PEDF protein is safe. PEDF protein alone or combined with VEGF antagonists shows similar efficacy in reducing pathological neovascularization and vessel obliteration as anti-VEGF agents. Furthermore, only treatments involving PEDF protein, alone or with VEGF antagonists, significantly improved the quality of retinal vasculature. Thus, PEDF protein alone or combined with anti-VEGF agents presents a promising alternative to current anti-VEGF treatments for ROP.

Association of Rate of Functional Recovery With Therapy Time and Content Among Adults With Acquired Brain Injuries in Inpatient Rehabilitation

ObjectiveTo examine associations among the time and content of rehabilitation treatment with self-care and mobility functional gain rate for adults with acquired brain injury. DesignRetrospective cohort study using electronic health record and administrative billing data. SettingInpatient rehabilitation unit at a large, academic medical center. ParticipantsAdults with primary diagnosis of stroke, traumatic brain injury, or nontraumatic brain injury admitted to the inpatient rehabilitation unit between 2012 and 2017 (N=799). InterventionsNot applicable. Main Outcome MeasuresGain rate in self-care and mobility function, using the Functional Independence Measure. Hierarchical regression models were used to identify the contributions of baseline characteristics, units, and content of occupational therapy, physical therapy, and speech-language pathology treatment to functional gain rates. ResultsMedian length of rehabilitation stay was 10 days (interquartile range, 8-13d). Patients received an mean of 10.62 units of therapy (SD, 2.05) daily. For self-care care gain rate, the best-fitting model accounted for 32% of the variance. Occupational therapy activities of daily living units were positively associated with gain rate. For mobility gain rate, the best-fitting model accounted for 37% of the variance. Higher amounts of physical therapy bed mobility training were inversely associated with mobility gain rate. ConclusionsMore activities of daily living in occupational therapy is associated with faster improvement on self-care function for adults with acquired brain injury, whereas more bed mobility in physical therapy was associated with slower improvement. A potential challenge with value-based payments is the alignment between clinically appropriate therapy activities and the metrics by which patient improvement are evaluated. There is a risk that therapists and facilities will prioritize activities that drive improvement on metrics and deemphasize other patient-centered goals.

Language networks of normal-hearing infants exhibit topological differences between resting and steady states: An fNIRS functional connectivity study.

Task-related studies have consistently reported that listening to speech sounds activate the temporal and prefrontal regions of the brain. However, it is not well understood how functional organization of auditory and language networks differ when processing speech sounds from its resting state form. The knowledge of language network organization in typically developing infants could serve as an important biomarker to understand network-level disruptions expected in infants with hearing impairment. We hypothesized that topological differences of language networks can be characterized using functional connectivity measures in two experimental conditions (1) complete silence (resting) and (2) in response to repetitive continuous speech sounds (steady). Thirty normal-hearing infants (14 males and 16 females, age: 7.8 ± 4.8 months) were recruited in this study. Brain activity was recorded from bilateral temporal and prefrontal regions associated with speech and language processing for two experimental conditions: resting and steady states. Topological differences of functional language networks were characterized using graph theoretical analysis. The normalized global efficiency and clustering coefficient were used as measures of functional integration and segregation, respectively. We found that overall, language networks of infants demonstrate the economic small-world organization in both resting and steady states. Moreover, language networks exhibited significantly higher functional integration and significantly lower functional segregation in resting state compared to steady state. A secondary analysis that investigated developmental effects of infants aged 6-months or below and above 6-months revealed that such topological differences in functional integration and segregation across resting and steady states can be reliably detected after the first 6-months of life. The higher functional integration observed in resting state suggests that language networks of infants facilitate more efficient parallel information processing across distributed language regions in the absence of speech stimuli. Moreover, higher functional segregation in steady state indicates that the speech information processing occurs within densely interconnected specialized regions in the language network.

Robotic-Assisted Total Knee Arthroplasty Results in Shorter Navigation Working Time With Similar Clinical Outcomes Compared to Computer-Navigated Total Knee Arthroplasty

BackgroundEarly clinical data are important in the appraisal of newly introduced robotic-assisted surgery (RAS) systems in total knee arthroplasty (TKA). However, there are few studies to date comparing 1-year clinical outcomes between RAS and computer-assisted navigation (CAS), the forerunner in reducing alignment outliers. The aim of this study was to determine if there was a difference between these two groups in early clinical outcomes, including functional outcome and patient-reported outcome measures (PROMs). MethodsA total of 158 propensity score-matched patients who underwent primary TKA with either CAS or RAS were retrospectively analyzed. Perioperative outcomes (navigation time, length of stay, complications, readmissions, transfusions, and technical failure), as well as functional outcome measures (range of motion, sit to stand test, timed-up-and-go test, single-leg stance test, calf raises, and step count), and PROMs (Oxford Knee Score, Knee Injury and Osteoarthritis Outcome Score, 12-item Short Form Survey, Forgotten Joint Score-12, and satisfaction) were compared between those who underwent CAS and those who underwent RAS. ResultsNavigation time was shorter in the RAS group compared to the CAS group (mean difference, 15.4 minutes; P < 0.001). There were 2 complications reported in the CAS group (one patellar clunk, one periprosthetic joint infection), but none in the RAS group. There were no other readmissions, transfusions, or technical failures in either group. Postoperatively, there were no clinical differences in function between groups. Clinically meaningful improvement in PROMs was observed in both groups, with no differences. ConclusionsThe use of RAS resulted in shorter navigation time compared to CAS in TKA. No other differences were observed in early clinical outcomes between patients who underwent RAS and CAS.