Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines.

Understanding vaccine-elicited protection against SARS-CoV-2 variants and other sarbecoviruses is key for guiding public health policies. We show that a clinical stage multivalent SARS-CoV-2 spike receptor-binding domain nanoparticle (RBD-NP) vaccine protects mice from SARS-CoV-2 challenge after a single immunization, indicating a potential dose-sparing strategy. We benchmarked serum neutralizing activity elicited by RBD-NPs in non-human primates against a lead prefusion-stabilized SARS-CoV-2 spike (HexaPro) using a panel of circulating mutants. Polyclonal antibodies elicited by both vaccines are similarly resilient to many RBD residue substitutions tested, although mutations at and surrounding position 484 have negative consequences for neutralization. Mosaic and cocktail nanoparticle immunogens displaying multiple sarbecovirus RBDs elicit broad neutralizing activity in mice and protect mice against SARS-CoV challenge even in the absence of SARS-CoV RBD in the vaccine. This study provides proof of principle that multivalent sarbecovirus RBD-NPs induce heterotypic protection and motivates advancing such broadly protective sarbecovirus vaccines to the clinic.

Potently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoprotein.

Human metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or treatment of hMPV-associated disease. Here, we used a high-throughput single-cell technology to interrogate memory B cell responses to the hMPV fusion (F) glycoprotein in young adult and elderly donors. Across all donors, the neutralizing antibody response was primarily directed to epitopes expressed on both pre- and post-fusion F conformations. However, we identified rare, highly potent broadly neutralizing antibodies that recognize pre-fusion-specific epitopes and structurally characterized an antibody that targets a site of vulnerability at the pre-fusion F trimer apex. Additionally, monotherapy with neutralizing antibodies targeting three distinct antigenic sites provided robust protection against lower respiratory tract infection in a small animal model. This study provides promising monoclonal antibody candidates for passive immunoprophylaxis and informs the rational design of hMPV vaccine immunogens.

Adjuvanting a subunit COVID-19 vaccine to induce protective immunity.

The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD-NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD-NP in AS03 (RBD-NP-AS03), and correlated with protection from infection. RBD-NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD-NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD-NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD-NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD-NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343).

Structure-based design of a soluble human cytomegalovirus glycoprotein B antigen stabilized in a prefusion-like conformation.

Human cytomegalovirus (HCMV) glycoprotein B (gB) is a class III membrane fusion protein required for viral entry. HCMV vaccine candidates containing gB have demonstrated moderate clinical efficacy, but no HCMV vaccine has been approved. Here, we used structure-based design to identify and characterize amino acid substitutions that stabilize gB in its metastable prefusion conformation. One variant containing two engineered interprotomer disulfide bonds and two cavity-filling substitutions (gB-C7), displayed increased expression and thermostability. A 2.8 Å resolution cryoelectron microscopy structure shows that gB-C7 adopts a prefusion-like conformation, revealing additional structural elements at the membrane-distal apex. Unlike previous observations for several class I viral fusion proteins, mice immunized with postfusion or prefusion-stabilized forms of soluble gB protein displayed similar neutralizing antibody titers, here specifically against an HCMV laboratory strain on fibroblasts. Collectively, these results identify initial strategies to stabilize class III viral fusion proteins and provide tools to probe gB-directed antibody responses.

Structural basis for ultrapotent antibody-mediated neutralization of human metapneumovirus.

Human metapneumovirus (hMPV) is a leading cause of morbidity and hospitalization among children worldwide, however, no vaccines or therapeutics are currently available for hMPV disease prevention and treatment. The hMPV fusion (F) protein is the sole target of neutralizing antibodies. To map the immunodominant epitopes on the hMPV F protein, we isolated a panel of human monoclonal antibodies (mAbs), and the mAbs were assessed for binding avidity, neutralization potency, and epitope specificity. We found the majority of the mAbs target diverse epitopes on the hMPV F protein, and we discovered multiple mAb binding approaches for antigenic site III. The most potent mAb, MPV467, which had picomolar potency, was examined in prophylactic and therapeutic mouse challenge studies, and MPV467 limited virus replication in mouse lungs when administered 24 h before or 72 h after viral infection. We determined the structure of MPV467 in complex with the hMPV F protein using cryo-electron microscopy to a resolution of 3.3 Å, which revealed a complex novel prefusion-specific epitope overlapping antigenic sites II and V on a single protomer. Overall, our data reveal insights into the immunodominant antigenic epitopes on the hMPV F protein, identify a mAb therapy for hMPV F disease prevention and treatment, and provide the discovery of a prefusion-specific epitope on the hMPV F protein.

Validation of the Machine Learning-Based Stroke Impact Scale With a Cross-Cultural Sample.

IMPORTANCE: The machine learning-based Stroke Impact Scale (ML-SIS) is an efficient short-form measure that uses 28 items to provide domain scores comparable to those of the original 59-item Stroke Impact Scale-Third Edition (SIS 3.0). However, its utility is largely unknown because it has not been cross-validated with an independent sample. OBJECTIVE: To examine the ML-SIS's comparability and test-retest reliability with that of the original SIS 3.0 in an independent sample of people with stroke. DESIGN: Comparability was examined with the coefficient of determination (R2), mean absolute error, and root-mean-square error (RMSE). Test-retest reliability was examined using the intraclass correlation coefficient (ICC). SETTING: Five hospitals in Taiwan. PARTICIPANTS: Data of 263 persons with stroke were extracted from a previous study; 144 completed repeated assessments after a 2-wk interval. RESULTS: High R2 (.87-.95) and low mean absolute error or RMSE (about 2.4 and 3.3) of the domain scores, except for the Emotion scores (R2 = .08), supported the comparability of the two measures. Similar ICC values (.39-.87 vs. .46-.87) were found between the two measures, suggesting that the ML-SIS is as reliable as the SIS 3.0. CONCLUSIONS AND RELEVANCE: The ML-SIS provides scores mostly identical to those of the original measure, with similar test-retest reliability, except for the Emotion domain. Thus, it is a promising alternative that can be used to lessen the burden of routine assessments and provide scores comparable to those of the original SIS 3.0. Plain-Language Summary: The machine learning-based Stroke Impact Scale (ML-SIS) is as reliable as the original Stroke Impact Scale-Third Edition, except for the Emotion domain. Thus, the ML-SIS can be used to improve the efficiency of clinical assessments and also relieve the burden on people with stroke who are completing the assessments.

Patient-Reported Variables Affecting Self-Perceived Overall Recovery Among People With Subacute Stroke.

IMPORTANCE: Patients' perception of overall recovery is a critical outcome for stroke rehabilitation. However, the perception of overall recovery cannot be obtained using multidimensional measures, because satisfaction in most domains of life does not guarantee satisfaction in overall recovery. A single overall recovery score seems a straightforward measure. However, the clinical implications of overall scores are restricted, because factors affecting patients' overall recovery are unclear, which can be prioritized to optimize the effectiveness of rehabilitation. OBJECTIVE: To examine patient-reported variables affecting overall recovery scores in patients with differing stroke severity. DESIGN: The 59 items of the Stroke Impact Scale 3.0 were selected using regression analysis with a forward selection to explain the overall recovery score (0% = no recovery; 100% = full recovery). Stroke severity was determined with the National Institutes of Health Stroke Scale. SETTING: Hospitals. PARTICIPANTS: Data of 950 patients collected 90 days after stroke. RESULTS: The models explained about 55% of the variance of the overall recovery scores with five to nine variables, but merely 16% of the variance was explained for patients with moderate stroke. As stroke severity increased, the number of identified variables decreased. Most identified variables were related to social participation and self-care activities (e.g., ability to help others, control the bowels, and dress the torso). Differences in the remaining variables depended on stroke severity. CONCLUSIONS AND RELEVANCE: Patients' priorities differ depending on stroke severity. The identified variables may be set as treatment goals to optimize patients' self-perceived overall recovery. Plain-Language Summary: How patients perceive their overall recovery after a stroke is a critical outcome for their stroke rehabilitation. This study demonstrated that patients with different stroke severity may have different priorities that influence their self-perceived levels of overall recovery. The variables identified in this study may help occupational therapy practitioners identify meaningful goals to optimize patients' self-perceived overall recovery.

Inter- and Intrarater Reliability of the Gap-Kalamazoo Communication Skills Assessment Form Among Occupational Therapy Interns.

IMPORTANCE: Effective communication skills (CS) are essential for occupational therapists. The Gap-Kalamazoo Communication Skills Assessment Form (GKCSAF) is a standard tool for assessing the CS of medical residents. However, the interrater reliability for the nine CS domain scores ranges from poor to good. The intrarater reliability remains unclear. OBJECTIVE: To examine the inter- and intrarater reliability of the GKCSAF's nine domain scores and total score among occupational therapy interns. DESIGN: Repeated assessments with the GKCSAF. SETTING: Medical center psychiatry department. PARTICIPANTS: Twenty-five interns and 49 clients with mental illness, recruited from August 2020 to December 2021. OUTCOMES AND MEASURES: The transcripts of 50 evaluation interviews between clients and interns were used. Three independent raters assessed each transcript twice, at least 3 mo apart. RESULTS: The GKCSAF demonstrated poor interrater reliability for the nine domain scores (weighted κ = .08-.30) and the total score (intraclass correlation coefficient [ICC] = .22, 95% confidence interval [CI] [.10, .35]). The GKCSAF showed poor to intermediate intrarater reliability for the nine domain scores (weighted κ = .27-.73) and fair reliability for the total score (ICC = .69, 95% CI [.60, .77]). CONCLUSIONS AND RELEVANCE: The GKCSAF demonstrates poor interrater reliability and poor to intermediate intrarater reliability for the nine domain scores. However, it demonstrates fair intrarater reliability in assessing the overall CS performance of occupational therapy interns. Significant variations were observed when different raters assessed the same interns' CS, indicating inconsistencies in ratings. Consequently, it is advisable to conservatively interpret the CS ratings obtained with the GKCSAF. Plain-Language Summary: It is essential for occupational therapists to effectively communicate with clients. The Gap-Kalamazoo Communication Skills Assessment Form (GKCSAF) is a standard tool that is used to assess the communication skills of medical residents. The study authors used the GKCSAF with occupational therapy interns in a medical center psychiatry department to assess how effectively they interviewed clients with mental illness. This study aids occupational therapy personnel in the interpretation of GKCSAF results. The study findings also highlight the importance of developing reliable and standardized measures to assess communications skills in the field of occupational therapy.

Development and validation of the Visual Function Battery for Children with Special Needs.

AIM: To develop and validate the Visual Function Battery for Children with Special Needs (VFB-CSN). METHOD: This was a scale development and validation study with (1) construct and item generation and (2) evaluations of interrater reliability, acceptability, and content, ecological, and convergent validities. RESULTS: Children with special needs were recruited for the reliability (n = 32) and validity (n = 95) investigations. The construct and items were generated based on literature review and an expert panel. We constructed eight categories, namely visual reflex, ocular muscle balance, visual acuity, oculomotor, visual field, contrast sensitivity, colour/form vision, and visual attention. Both functional assessment and standardized tests were adopted. The reliabilities were high for the whole VFB-CSN (intraclass correlation coefficient [ICC] = 0.90, 95% confidence interval [CI] = 0.80-0.90) and good for the oculomotor, contrast sensitivity, and colour/form vision (ICC = 0.80-0.86, 95% CI = 0.50-0.93). Correlations between the VFB-CSN and the Functional Vision Questionnaire were strong and acceptable for the contrast sensitivity, acuity, and colour/form vision (r = 0.79, r = 0.69, r = 0.69, r = 0.70 respectively). The correlation between the VFB-CSN and standardized visual acuity test was acceptable (r = -0.72). INTERPRETATION: The VFB-CSN is a reliable and valid multifaceted battery for children with special needs. Acceptable psychometric properties were also found for the acuity and contrast sensitivity. WHAT THIS PAPER ADDS: The Visual Function Battery for Children with Special Needs (VFB-CSN) can measure several types of visual function. The VFB-CSN also measures varying degrees of visual impairment in children with special needs. The VFB-CSN provides functional assessment and quantitative measurement for children with disability and difficulty in cooperating on standardized tests.

Development of a Berg Balance Scale Short-Form Using a Machine Learning Approach in Patients With Stroke.

BACKGROUND AND PURPOSE: The Berg Balance Scale (BBS) is frequently used in routine clinical care and research settings and has good psychometric properties. This study was conducted to develop a short form of the BBS using a machine learning approach (BBS-ML). METHODS: Data of 408 individuals poststroke were extracted from a published database. The initial (ie, 4-, 5-, 6-, 7-, and 8-item) versions were constructed by selecting top-ranked items based on the feature selection algorithm in the artificial neural network model. The final version of the BBS-ML was chosen by selecting the short form that used a smaller number of items to achieve a higher predictive power R2 , a lower 95% limit of agreement (LoA), and an adequate possible scoring point (PSP). An independent sample of 226 persons with stroke was used for external validation. RESULTS: The R2 values for the initial 4-, 5-, 6-, 7-, and 8-item short forms were 0.93, 0.95, 0.97, 0.97, and 0.97, respectively. The 95% LoAs were 14.2, 12.2, 9.7, 9.6, and 8.9, respectively. The PSPs were 25, 35, 34, 35, and 36, respectively. The 6-item version was selected as the final BBS-ML. Preliminary external validation supported its performance in an independent sample of persons with stroke ( R2 = 0.99, LoA = 10.6, PSP = 37). DISCUSSION AND CONCLUSIONS: The BBS-ML seems to be a promising short-form alternative to improve administrative efficiency. Future research is needed to examine the psychometric properties and clinical usage of the 6-item BBS-ML in various settings and samples.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A402 ).

Development of a 13-item Short Form for Fugl-Meyer Assessment of Upper Extremity Scale Using a Machine Learning Approach.

OBJECTIVE: To develop and validate a short form of the Fugl-Meyer Assessment of Upper Extremity Scale (FMA-UE) using a machine learning approach (FMA-UE-ML). In addition, scores of items not included in the FMA-UE-ML were predicted. DESIGN: Secondary data from a previous study, which assessed individuals post-stroke using the FMA-UE at 4 time points: 5-30 days post-stroke screen, 2-month post-stroke baseline assessment, 6-month post-stroke assessment, and 12-month post-stroke assessment. SETTING: Rehabilitation units in hospitals. PARTICIPANTS: A total of 408 individuals post-stroke (N=408). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The 30-item FMA-UE. RESULTS: We established 29 candidate versions of the FMA-UE-ML with different numbers of items, from 1 to 29, and examined their concurrent validity and responsiveness. We found that the responsiveness of the candidate versions obviously declined when the number of items was less than 13. Thus, the 13-item version was selected as the FMA-UE-ML. The concurrent validity was good (intra-class correlation coefficients ≥0.99). The standardized response means of the FMA-UE-ML and FMA-UE were 0.54-0.88 and 0.52-0.91, respectively. The Pearson's rs between the change scores of the FMA-UE-ML and those of the FMA-UE were 0.96-0.98. The predicted item scores had acceptable to good accuracy (Kappa=0.50-0.92). CONCLUSIONS: The FMA-UE-ML seems a promising short form to improve administrative efficiency while retaining good concurrent validity and responsiveness. In addition, the FAM-UE-ML can provide all item scores of the FMA-UE for users.

Test-Retest Reliability and Responsiveness of the Computerized Adaptive Testing System of the Functional Assessment of Stroke.

OBJECTIVE: To examine the test-retest reliability, responsiveness, and clinical utility of the Computerized Adaptive Testing System of the Functional Assessment of Stroke (CAT-FAS) in persons with stroke. DESIGN: Repeated measurements design. SETTING: A department of rehabilitation in a medical center. PARTICIPANTS: 30 persons with chronic stroke (for test-retest reliability) and 65 persons with subacute stroke (for responsiveness) were recruited. To examine the test-retest reliability, the participants received measurements twice at 1-month intervals. To examine the responsiveness, the data were collected at admission and discharge from hospital. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASUREMENT TOOL: CAT-FAS. RESULTS: The intra-class correlation coefficients of the CAT-FAS were ≥0.82, indicating good to excellent test-retest reliability. The Kazis' effect size and standardized response mean of the CAT-FAS were ≥0.96, indicating good group-level responsiveness. For individual-level responsiveness, approximately two-thirds of the participants exceeded the conditional minimal detectable change. On average, the CAT-FAS was completed within 9 items and 3 minutes per administration. CONCLUSIONS: Our results suggest the CAT-FAS is an efficient measurement tool with good to excellent test-retest reliability and responsiveness. In addition, the CAT-FAS can be used routinely in clinical settings to monitor progress of the crucial 4 domains for persons with stroke.

Test-Retest Reliability and Responsiveness of the Computerized Adaptive Test of Social Functioning in Persons With Stroke.

OBJECTIVE: To examine the test-retest reliability, minimal detectable change (MDC), responsiveness, and efficiency of the Computerized Adaptive Test of Social Functioning (Social-CAT) in patients with stroke. DESIGN: Repeated-assessments design. SETTING: A department of rehabilitation of a medical center. PARTICIPANTS: In total, 31 patients with chronic stroke and 65 patients with subacute stroke were recruited. INTERVENTION: Not available. MAIN OUTCOME MEASURE: Social-CAT. RESULTS: The Social-CAT showed acceptable test-retest reliability (intraclass correlation coefficient, 0.80) and small random measurement error (MDC%: 18.0%). However, heteroscedasticity was found (r between the means and the absolute change scores: 0.32), so the MDC% adjusted cut-off score is recommended for determining real improvement. Regarding responsiveness, the Social-CAT showed large differences (Kazis' effect size and standardized mean response: 1.15 and 1.09, respectively) in subacute patients. Regarding efficiency, the Social-CAT required an average of 5 items and less than 2 minutes for completion. CONCLUSIONS: Our findings indicate that the Social-CAT is a reliable and efficient measure with good test-retest reliability, small random measurement error, and good responsiveness. Thus, the Social-CAT is a useful outcome measure for routine monitoring of the changes in social function of patients with stroke.

Using Artificial Intelligence to Identify the Associations of Children's Performance of Coloring, Origami, and Copying Activities With Visual-Motor Integration.

IMPORTANCE: Performance of coloring, origami, and copying activities reflects children's visual-motor integration (VMI), but the levels of association remain unclear. OBJECTIVE: To use artificial intelligence (AI) to investigate associations of performance of coloring, origami, and copying activities with VMI. DESIGN: Cross-sectional study. SETTING: Kindergartens. PARTICIPANTS: A sample of 370 children (182 boys and 188 girls) in the second and third years of kindergarten. OUTCOMES AND MEASURES: Beery-Buktenica Developmental Test of Visual-Motor Integration, 6th Edition (VMI-6). RESULTS: Data for preschool children from an ongoing project were retrieved. AI models were trained to use photographs of activity products to predict total score on the VMI-6. R2 values were used to identify the variance in VMI-6 standardized scores explained by predicted scores from the activities. That is, R2 values reflected associations between activity performance and VMI. The R2 values for the combination of origami and copying were the largest (.390-.577). These R2 values were larger than those for each individual activity (.340-.473) and similar to those for the combination of all three activities (.400-.550). CONCLUSIONS AND RELEVANCE: Because moderate R2 values were found between performance of the three activity products and VMI, the three activities have high potential for use in identifying children's level of VMI or as teaching materials to facilitate the development of children's VMI. Furthermore, combining origami and copying activities is recommended for teachers and clinicians who need to address VMI. What This Article Adds: A combination of origami and copying activities had the strongest associations with children's VMI. Teachers and clinicians can use these two activities when addressing VMI development among preschool children.

A vulnerable, membrane-proximal site in human respiratory syncytial virus F revealed by a prefusion-specific single-domain antibody.

Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease, especially in young children and the elderly. The fusion protein (F) exists in a pre- and postfusion conformation and is the main target of RSV-neutralizing antibodies. Highly potent RSV-neutralizing antibodies typically bind sites that are unique to the prefusion conformation of F. In this study we screened a single-domain antibody (VHH) library derived from a llama immunized with prefusion-stabilized F and identified a prefusion F-specific VHH that can neutralize RSV A at subnanomolar concentrations. Structural analysis revealed that this VHH primarily binds to antigenic site I while also making contacts with residues in antigenic site III and IV. This new VHH reveals a previously underappreciated membrane-proximal region sensitive for neutralization.ImportanceRSV is an important respiratory pathogen. This study describes a prefusion F-specific VHH that primarily binds to antigenic site I of RSV F. This is the first time that a prefusion F-specific antibody that binds this site is reported. In general, antibodies that bind to site I are poorly neutralizing, whereas the VHH described here neutralizes RSV A at subnanomolar concentrations. Our findings contribute to insights into the RSV F antigenic map.

Using Machine Learning to Develop a Short-Form Measure Assessing 5 Functions in Patients With Stroke.

OBJECTIVE: This study aimed to develop and validate a machine learning-based short measure to assess 5 functions (the ML-5F) (activities of daily living [ADL], balance, upper extremity [UE] and lower extremity [LE] motor function, and mobility) in patients with stroke. DESIGN: Secondary data from a previous study. A follow-up study assessed patients with stroke using the Barthel Index (BI), Postural Assessment Scale for Stroke (PASS), and Stroke Rehabilitation Assessment of Movement (STREAM) at hospital admission and discharge. SETTING: A rehabilitation unit in a medical center. PARTICIPANTS: Patients (N=307) with stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The BI, PASS, and STREAM. RESULTS: A machine learning algorithm, Extreme Gradient Boosting, was used to select 15 items from the BI, PASS, and STREAM, and transformed the raw scores of the selected items into the scores of the ML-5F. The ML-5F demonstrated good concurrent validity (Pearson's r, 0.88-0.98) and responsiveness (standardized response mean, 0.28-1.01). CONCLUSIONS: The ML-5F comprises only 15 items but demonstrates sufficient concurrent validity and responsiveness to assess ADL, balance, UE and LE functions, and mobility in patients with stroke. The ML-5F shows great potential as an efficient outcome measure in clinical settings.

Rasch Analysis of the Stroke Impact Scale-16.

IMPORTANCE: Because the psychometric evidence supporting the use of the Stroke Impact Scale-16 (SIS-16) is limited, an examination of its psychometric properties is warranted. OBJECTIVE: To evaluate the psychometric properties of the SIS-16 using Rasch analysis. DESIGN: Secondary data analysis of responses to the SIS-16 from the published Field Administration of Stroke Therapy-Magnesium Trial database. SETTING: Emergency medical system agencies and acute care receiving hospitals. PARTICIPANTS: A total of 1,010 people with stroke. OUTCOMES AND MEASURES: We examined the item difficulty hierarchy, item fit, person-item match, separation index, person reliability coefficient, and ceiling and floor effect of the SIS-16. RESULTS: The item "climb a flight of stairs" was the most difficult, and "sit without losing balance" was the easiest. Four items misfit the Rasch partial-credit measurement model. Overall, the average patient ability estimate of 2.1 logits (SD = 2.0) was higher than the average item difficulty estimate of 0.0 logits (SD = 1.1). With a separation index of 2.85, the SIS-16 can differentiate people into 4.1 statistically distinct strata. The person reliability coefficient was .89. Given that 24.2% (n = 244) obtained the maximum score and 0.2% (n = 2) obtained the minimum score, the SIS-16 had a ceiling effect in this patient sample. CONCLUSIONS AND RELEVANCE: Results partially support the validity and clinical use of the SIS-16 in subacute stroke clinical settings. Further research is warranted to examine the psychometric properties of the SIS-16 in patients with chronic stroke. What This Article Adds: Our results partially support the use of the SIS-16 in clinical and research settings.

Assessment of Low Back Pain: Reliability and Minimal Detectable Change of the Brief Pain Inventory.

IMPORTANCE: The Brief Pain Inventory (BPI) is one of the most widely used measures to assess pain and related impacts among patients with low back pain (LBP). However, its test-retest reliability and minimal detectable change (MDC) have rarely been examined in patients with LBP, interfering with its utility. OBJECTIVE: To investigate the test-retest reliability and MDC of the BPI among patients with LBP. DESIGN: Repeated assessments design with a 1-wk interval. SETTING: Department of Physical Medicine and Rehabilitation in a hospital in Taiwan. PARTICIPANTS: Fifty-four patients with stable LBP conditions. OUTCOMES AND MEASURES: The BPI has two subscales-Intensity and Interference-that assess pain intensity and pain interference, respectively. Their test-retest reliability was examined using the intraclass correlation coefficient (ICC), and MDCs were calculated. RESULTS: The ICCs of the Intensity and Interference subscales were .62 and .76, respectively. The MDC values for the two subscales were 2.57 and 2.34, respectively. For the four Intensity items, the average-pain score had a higher ICC (.60) than scores on the other items (worst, least, and current pain, which had ICCs of about .40). CONCLUSIONS AND RELEVANCE: The results suggest that although the BPI is a commonly used measure of pain intensity and pain interference among patients with LBP, caution should be exercised in interpreting the Intensity subscale score and its item scores. What This Article Adds: The BPI is widely used to assess pain and related impacts on daily occupation and functioning among patients with LBP. This study provides information regarding its test-retest reliability. Moreover, the MDC values provide clinicians and researchers with the thresholds for determining real improvement (beyond random measurement error).

Development of a Short-Form Stroke Impact Scale Using a Machine Learning Algorithm for Patients at the Subacute Stage.

IMPORTANCE: Several short forms of the Stroke Impact Scale Version 3.0 (SIS 3.0) have been proposed in order to decrease its administration time of about 20 min. However, none of the short-form scores are comparable to those of the original measure. OBJECTIVE: To develop a short-form SIS 3.0 using a machine learning algorithm (ML-SIS). DESIGN: We developed the ML-SIS in three stages. First, we calculated the frequencies of items having the highest contribution to predicting the original domain scores across 50 deep neural networks. Second, we iteratively selected the items showing the highest frequency until the coefficient of determination (R2) of each domain was ≥.90. Third, we examined the comparability and concurrent and convergent validity of the ML-SIS. SETTING: Hospitals. PARTICIPANTS: We extracted complete data for 1,010 patients from an existing data set. RESULTS: Twenty-eight items were selected for the ML-SIS. High average R2s (.90-.96) and small average residuals (mean absolute errors and root-mean-square errors = 0.49-2.84) indicate good comparability. High correlations (rs = .95-.98) between the eight domain scores of the ML-SIS and the SIS 3.0 indicate sufficient concurrent validity. Similar interdomain correlations between the two measures indicate satisfactory convergent validity. CONCLUSIONS AND RELEVANCE: The ML-SIS uses about half of the items in the SIS 3.0, has an estimated administration time of 10 min, and provides valid scores comparable to those of the original measure. Thus, the ML-SIS may be an efficient alternative to the SIS 3.0. What This Article Adds: The ML-SIS, a short form of the SIS 3.0 developed using a machine learning algorithm, shows good potential to be an efficient and informative measure for clinical settings, providing scores that are valid and comparable to those of the original measure.

Test-retest reliability and convergent validity of the test of nonverbal intelligence-fourth edition in patients with schizophrenia.

BACKGROUND: Fluid intelligence deficits affect executive functioning and social behaviors in patients with schizophrenia. To help clinicians manage fluid intelligence deficits, a psychometrically sound measure is needed. The purposes of this study were to examine the test-retest reliability and convergent validity of the Test of Nonverbal Intelligence-Fourth Edition (TONI-4) assessing fluid intelligence in patients with schizophrenia. METHODS: A total of 103 patients with stable condition were assessed with the TONI-4 twice with a 4-week interval to examine the test-retest reliability. We further used the Montreal Cognitive Assessment (MoCA) and the Tablet-Based Symbol Digit Modalities Test (T-SDMT) to examine the convergent validity of the TONI-4. RESULTS: The intra-class correlation coefficient was 0.73 for the TONI-4. The percentages of standard error of measurement and minimal detectable change for the TONI-4 were 5.1 and 14.2%, respectively. The practice effect of the TONI-4 was small (Cohen's d = - 0.03). Convergent validity showed small to moderate significant correlations between the TONI-4 and the MoCA as well as the T-SDMT (r = 0.35, p = .011 with the T-SDMT and r = 0.61, p < .001 with the MoCA). The results demonstrated that the TONI-4 had good test-retest reliability, limited random measurement error, and a trivial practice effect. The convergent validity of the TONI-4 was good. CONCLUSIONS: These findings indicate that the TONI-4 has potential to be a reliable and valid assessment of fluid intelligence in patients with schizophrenia.