Outcome Measure In Clinical Studies Research Articles

Large scale serum proteomics identifies proteins associated with performance decline and clinical milestones in Duchenne muscular dystrophy.

Serum biomarkers are promising minimally invasive outcome measures in clinical studies in Duchenne muscular dystrophy (DMD). However, biomarkers strongly associated with clinical progression and predicting performance decline are lacking. In this study we aimed to identify serum biomarkers associated with clinical performance and able to predict clinical milestones in DMD. Towards this aim we present a retrospective multi-center cohort study including serum samples and clinical data collected in research participants with DMD as part of a natural history study at the University of Florida (UF) and real-world observations at Leiden University Medical Center (LUMC) between 2009-2022. The 7K SomaScan® assay was used to analyse protein levels in in individual serum samples. Serum biomarkers predicted age at loss of ambulation (LoA), age at loss of overhead reach (OHR) and age at loss of hand to mouth function (HTM). Secondary outcomes were the association of biomarkers with age, corticosteroid (CS) usage, and clinical performance based on the North Star Ambulatory Assessment (NSAA), 10 meter run velocity (10mrv), 6 minute walk (6MWT) and Performance of the Upper Limb (PUL2.0). A total of 716 serum samples were collected in 79 participants at UF and 74 at LUMC (mean[SD] age; 10.9[3.2] vs 8.4[3.4]). 244 serum proteins showed an association with CS usage in both cohorts independent of CS type and regimen, including MMP3 and IGLL1. 318 probes (corresponding to 294 proteins) showed significant associations with NSAA, 10mrv, 6MWT and/or PUL2.0 across both cohorts. The expression of 38 probes corresponding to 36 proteins such as RGMA, EHMT2, ART3, ANTXR2 and DLK1 was associated with risk of both lower and upper limb clinical milestones in both the LUMC and UF cohort. In conclusion, multiple biomarkers were associated with CS use, motor function and upper lower and upper limb disease milestones in DMD. These biomarkers were validated across two independent cohorts, increasing their likelihood of translation for use within the broader DMD population.

The methodological quality of systematic reviews regarding the Core Outcome Set (COS) development

BackgroundThe Core Outcome Measures in Effectiveness Trials (COMET) working group proposed core outcome sets (COS) to address the heterogeneity in outcome measures in clinical studies. According to the recommendations of COMET, performing systematic reviews (SRs) usually was the first step for COS development. However, the SRs that serve as a basis for COS are not specifically appraised by organizations such as COMET regarding their quality. Here, we investigated the status of SRs related to development of COS and evaluated their methodological quality.MethodsWe conducted a search on PubMed to identify SRs related to COS development published from inception to May 2022. We qualitatively summarized the disease included in SR topics, and the studies included in the SRs. We evaluated the methodological quality of the SRs using AMSTAR 2.0 and compared the overall quality of SRs with and without protocols using the Mann-Whitney U test.ResultsWe included 175 SRs from 23 different countries or regions, and they mainly focused on five diseases: musculoskeletal system or connective tissue disease (n = 19, 10.86%), injury, poisoning, or certain other consequences of external causes (n = 18, 10.29%), digestive system disease (n = 16, 9.14%), nervous system disease (n = 15, 8.57%), and genitourinary system disease (n = 15, 8.57%). Although 88.00% of SRs included randomized controlled trials (RCTs), only a few SRs (23.38%) employed appropriate tools to assess the risk of bias in RCTs. The assessment results on the basis of AMSTAR 2.0 indicated that most SRs (93.71%) were rated as ‘’critically low’’ to ‘’low’’ in terms of overall confidence. The overall confidence of SRs with protocols was significantly higher than that without protocols (P <.001). Compared to the SRs with protocols on Core Outcome Measures in Effectiveness Trials (COMET), SRs with protocols on PROSPERO were of better overall confidence (P = .017).ConclusionThe overall quality of published SRs regarding COS development was poor. Our findings emphasize the need for researchers to carefully select the disease topic and strictly adhere to the requirements of optimal methodology when conducting a SR for the establishment of a COS.

Interobserver agreement of current and new proposed endoscopic scores for postoperative recurrence in Crohn’s disease

Background and AimsThe modified Rutgeerts’ score (mRS) is widely used for the assessment of endoscopic postoperative recurrence (ePOR) in Crohn’s disease (CD) after ileocolic resection to guide therapeutic decisions. To improve the validity and prognostic value of this endoscopic assessment, two new scores have been proposed. This study assessed the interobserver agreement of the current (mRS) and new endoscopic scores for ePOR in CD. MethodsSixteen Dutch academic and non-academic IBD specialists assessed endoscopic videos (n=71) of postoperative CD patients (n=66) retrieved from nine Dutch centers. Each video was assessed for the degree of inflammation by four gastroenterologists using the mRS and the new proposed endoscopic score: REMIND score (separate score of anastomosis and neoterminal ileum) and updated Rutgeerts score (assessment of lesions at the anastomotic line, ileal inlet, ileal body and neoterminal ileum). In addition, lesions at the ileal body, ileal inlet, neoterminal ileum, colonic and/or ileal blind loop were separately assessed. Interobserver agreement was assessed using Fleiss’ weighted kappa. ResultsFleiss’ weighted kappa for the mRS was 0.67 (95% confidence interval [CI] 0.59–0.74). The weighted kappa for the REMIND score was 0.73 (95% CI 0.65–0.80) for lesions in the neoterminal ileum and 0.46 (95% CI 0.35–0.58) for anastomotic lesions. The weighted kappa for the updated Rutgeerts’ score was 0.69 (95% CI 0.62–0.77). The weighted kappa for lesions in the ileal body, ileal inlet, neoterminal ileum, colonic and ileal blind loop was 0.61 (95% CI 0.49–0.73), 0.63 (95% CI 0.54–0.72), 0.61 (95% CI 0.49–0.74), 0.83 (95% CI 0.62–1.00) and 0.68 (95% CI 0.46–0.89). ConclusionThe interobserver agreement of the mRS is substantial. Similarly, the interobserver agreement is substantial for the updated Rutgeerts’ score. According to the REMIND score, the interobserver agreement was substantial for lesions in the neoterminal ileum, whereas only moderate for anastomotic lesions. Since therapeutic decisions in clinical practice are based on these assessments and these scores are used as outcome measure in clinical studies, further improvement of the interobserver agreement is essential.

P277 Interobserver agreement of current and new proposed endoscopic scores for postoperative recurrence in Crohn’s disease

Abstract Background The modified Rutgeerts’ score (mRS) is widely used for the assessment of endoscopic postoperative recurrence (ePOR) in Crohn’s disease (CD) after ileocolic resection to guide therapeutic decisions. To improve the validity and prognostic value of this endoscopic assessment, two new scores have been proposed. This study assessed the interobserver agreement of the current (mRS) and new endoscopic scores for ePOR in CD. Methods Sixteen academic and non-academic IBD specialists assessed endoscopic videos (n=71) of postoperative CD patients (n=66) retrieved from nine Dutch centers. Each video was assessed for the degree of inflammation by four gastroenterologists using the mRS, REMIND score (separate score of anastomosis and neoterminal ileum) and anatomic score (separate score of lesions at the anastomotic line, ileal body, ileal inlet, neoterminal ileum, colonic and/or ileal blind loop). Interobserver agreement was assessed using Fleiss’ weighted kappa. Results Fleiss’ weighted kappa for the mRS was 0.67 (95% confidence interval [CI] 0.59–0.74). The weighted kappa for the REMIND score was 0.73 (95% CI 0.65–0.80) for lesions in the neoterminal ileum and 0.46 (95% CI 0.35–0.58) for anastomotic lesions. In the anatomic score, the weighted kappa for lesions in the ileal body, ileal inlet, neoterminal ileum, colonic and ileal blind loop was 0.61 (95% CI 0.49–0.73), 0.63 (95% CI 0.54–0.72), 0.61 (95% CI 0.49–0.74), 0.83 (95% CI 0.62–1.00) and 0.68 (95% CI 0.46–0.89), and 0.44 (95% CI 0.32–0.55) for lesions at the anastomotic line. Conclusion The interobserver agreement of the mRS is substantial. Similarly, the interobserver agreement is substantial for lesions in the neoterminal ileum according to both the REMIND and anatomic score, whereas only moderate for anastomotic lesions. Since therapeutic decisions in clinical practice are based on these assessments and these scores are used as outcome measure in clinical studies, further improvement of agreement is essential.

Head and Neck Cancer: A Study on the Complex Relationship between QoL and Swallowing Function.

Head and neck squamous cell carcinoma (HNSCC) is linked to significant morbidity, adversely affecting survival and functional capacity. Post-treatment challenges such as pain, dysphonia, and dysphagia are common, prompting increased attention in survivorship research. Quality of Life (QoL) questionnaires, especially the MD Anderson Dysphagia Inventory (MDADI), are prevalent outcome measures in clinical studies but often lack parallel objective swallowing function evaluations, leading to potential outcome discrepancies. This study aimed to illuminate the relationship between subjective QoL (EQ-5D-5L and MDADI) measures and objective swallowing function (evaluated via Fiberoptic Endoscopic Evaluation of Swallowing, FEES) in patients with HNSCC. The analysis revealed a notable discordance between objective measures of swallowing function, such as the Penetration-Aspiration Scale (PAS) and residue ratings in the vallecula or piriform sinus, and patients' subjective QoL assessments (p = 0.21). Despite the lack of correlation, swallowing-related QoL, as measured by the MDADI, was more indicative of disease severity than generic QoL assessments. Generic QoL scores did not demonstrate substantial variation between patients. In contrast, MDADI scores significantly declined with advancing tumor stage, multimodal therapy, and reliance on feeding tubes. However, the clinical significance of this finding was tempered by the less than 10-point difference in MDADI scores. The findings of this study underline the limitations of QoL measures as standalone assessments in patients with HNSCC, given their reliance on patient-perceived impairment. While subjective QoL is a crucial aspect of evaluating therapeutic success and patient-centric outcomes, it may fail to capture critical clinical details such as silent aspirations. Consequently, QoL assessments should be augmented by objective evaluations of swallowing function in clinical research and practice to ensure a holistic understanding of patient well-being and treatment impact.

Current status of clinical outcome measures in inclusion body myositis: a systematised review.

Sporadic inclusion body myositis (IBM) is a debilitating idiopathic inflammatory myopathy (IIM) which affects hand function, ambulation, and swallowing. There is no approved pharmacological therapy for IBM, and there is a lack of suitable outcome measure to assess the effect of an intervention. The IBM scientific interest group under IMACS reviewed the previously used outcome measures in IBM clinical studies to lay the path for developing a core set of outcome measures in IBM. In this systematised review, we have extracted all outcome measures reported in IBM clinical studies to determine what measures were being used and to assess the need for optimising outcome measures in IBM. We found 13 observational studies, 17 open-label clinical trials, and 15 randomised control trials (RCTs) in IBM. Six-minute walk distance, IBM-functional rating scale (IBM-FRS), quantitative muscle testing, manual muscle testing, maximal voluntary isometric contraction testing, and thigh muscle volume measured by MRI were used as primary outcome measures. Twelve different outcome measures of motor function were used in IBM clinical trials. IBM-FRS was the most used measure of functionality. Swallowing function was reported as a secondary outcome measure in only 3 RCTs. There are inconsistencies in using outcome measures in clinical studies in IBM. The core set measures developed by the IMACS group for other IIMs are not directly applicable to IBM. As a result, there is an unmet need for an IBM-specific core set of measures to facilitate the evaluation of new potential therapeutics for IBM.

Comparisons Among Optical Coherence Tomography and Fundus Autofluorescence Modalities as Measurements of Atrophy in ABCA4-Associated Disease

PurposeIn ABCA4-associated retinopathy, central atrophy was assessed by spectral domain optical coherence tomography (SD-OCT) and by short-wavelength (SW-AF) and near-infrared (NIR-AF) autofluorescence.MethodsPatients exhibited a central atrophic lesion characterized by hypoautofluorescence (hypoAF) surrounded either by hyperautofluorescent (hyperAF) rings in both AF images (group 1, 4 patients); or a hyperAF ring in SW-AF but not in NIR-AF images (group 2, 11 patients); or hyperAF rings in neither AF images (group 3, 11 patients). Choroidal hypertransmission and widths of ellipsoid zone (EZ) loss were measured in foveal SD-OCT scans, and in AF images hypoAF and total hypo+hyperAF widths were measured along the same axis. Bland-Altman and repeated measures analysis of variance with Tukey post hoc were applied.ResultsFor all groups, hypertransmission widths were significantly smaller than EZ loss widths. In Groups 1 and 2, hypertransmission width was not significantly different than SW-hypoAF width, but hypertransmission was narrower than the width of SW-hypo+hyperAF (groups 1, 2) and NIR-hypo+hyperAF (group 1). In group 3, the hypertransmission width was also significantly less than the width of SW-hypoAF and NIR-hypoAF. The EZ loss widths were not significantly different than measurements of total lesion size, the latter being the widths of SW-hypo+hyperAF and NIR-hypo+hyperAF (group 1); widths of NIR-hypoAF and SW-hypo+hyperAF (group 2); and widths of NIR-hypoAF and SW-hypoAF (group 3).ConclusionsHypertransmission and SW-hypoAF (except when reflecting total lesion width) underestimate lesion size detected by EZ loss, SW-hypoAF+hyperAF, and NIR-hypo+hyperAF.Translational RelevanceThe findings are significant to the selection of outcome measures in clinical studies.

A Comparison of Health Status and Quality of Life in Patients with Intermittent Claudication

Patient reported outcome measures (PROMs) such as health status (HS) and quality of life (QOL) are frequently used interchangeably while they represent different outcomes. Whether a discrepancy exists in patients with intermittent claudication (IC) in changes over time between HS and QOL is unclear. This study aimed to investigate the strength and the direction of the association between HS and QOL over time in patients with IC that underwent supervised exercise therapy (SET). Patients were part of the ELECT multi-center prospective cohort study. One goal of this study was to obtain data on HS and QOL at different time intervals of patients with IC that underwent SET. HS (VascuQOL-6) and QOL (WHOQOL-BREF) were completed at baseline, 3 months, and 6 months follow up. Pearson's correlation coefficients and the associated common variances (R2) were calculated to measure the strength and the direction of the association between HS and QOL in changes between baseline and follow-up moments. In total, 177 patients were included in data analyses. Only changes in physical QOL and overall QOL had a small correlation with changes over time in HS, at both 3- and 6 months follow up (respectively R2=.14; P < 0.001 and R2=0.12; P < 0.001 for physical QOL and R2=0.18; P < 0.001 and R2=0.13; P < 0.001 for overall QOL). This study showed that HS and QOL provide different outcomes in patients with IC that underwent SET. Future studies should be aware of these differences before PROMs are being incorporated as an outcome measure in clinical studies.

Assessment of Quality of Life Between Patients Undergoing Pharmacomechanical Catheter-Directed Thrombolysis Versus Conservative Management with Iliofemoro-Popliteal Deep-Vein Thrombosis

Background: Pharmacomechanical catheter-directed thrombolysis (PCDT) has revolutionized the treatment of acute deep-vein thrombosis (DVT). Assessment and comparison of quality of life (QOL) in patients treated with anticoagulation alone and PCDT need to be elaborated more in the context of better management of patients. The objective of this study was to compare and assess QOL using health-related QOL (HRQOL) which includes short form-36 (SF-36) and VIENES QOL/sym scoring systems in anticoagulation alone group and patients treated with PCDT. Methods: There were 130 consecutive patients presenting to our department with acute iliofemoro-popliteal DVT (IFPDVT) with &lt;2 weeks duration treated between April 2018 and April 2019 were included in the study. Sixty-five patients received anticoagulation alone and the other 65 patients received PCDT along with anticoagulation. Patients were assessed at baseline, the 1st month, and the 6th month in terms of QOL, deep venous patency (DVP), and deep venous reflux (DVR). Results: There was a statistically significant difference between the two groups in terms of QOL at 1st and 6 months. Mean physical component score and mental component score were statistically significantly better in PCDT than the conservative group at 1 and 6 months, respectively (P = 0.001). Mean venous insufficiency epidemiological and economic study (VEINES) QOL and VEINES SYM scores were significantly better in PCDT group than conservative group at 1 and 6 months, respectively (P = 0.001). Conclusion: QOL, DVP, and DVR are significantly better when PCDT is offered as an initial option when compared to anticoagulation alone. HRQOL (SF 36 and VEINESQOL/SYM score) should be considered as an outcome measure in clinical studies on patients with IFPDVT along with other comparison parameters with respect to QOL. However, long-term follow-up is required to establish the superiority of PCDT in IFPDVT patients.

Validity and reliability of the QLQ-MY20 module for assessing the health-related quality of life in Brazilians with multiple myeloma

Purpose Multiple myeloma (MM) is a rare but treatable hematological cancer, which makes the health-related quality of life (HRQoL) an important patient-report outcome measure in clinical studies. The Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY20) was developed by the European Organization for Research and Treatment of Cancer (EORTC) to measure HRQoL in people with MM. However, the Brazilian Portuguese version of QLQ-MY20 has not yet been validated for Brazil. This study aimed to evaluate the validity and reliability of the instrument for application in Brazilian patients with MM. Methods This is a cross-sectional methodological study with patients seen in health services in Belo Horizonte, Brazil. The variables were collected through face-to-face interviews with the QLQ-MY20 instrument and complemented with data from medical records. Content validity analyses (content validity coefficient [CVC]; correctness ratio), convergent and divergent validity (Spearman’s correlation coefficient [CC]), internal consistency, and temporal reproducibility (test–retest; intraclass correlation coefficient [ICC]) were performed. Results 225 patients were included and 71.1% were older than 60. The analysis of the judging committee showed adequate content validity. We observed mainly a good internal consistency of the items and good discrimination power in the convergent and divergent validity. High ICC values were observed through the test–retest, and there was no difference in the scores between the two moments, which shows good temporal stability of the instrument. Conclusion The study allowed us to conclude that the Brazilian version of the QLQ-MY20 module is valid and reliable, and thus suitable for application in Brazilians living with MM.

Hand Dexterity and Pyramidal Dysfunction in Friedreich Ataxia, A Finger Tapping Study.

Loss of hand dexterity has a profound impact on disability in patients with cerebellar, pyramidal, or extrapyramidal diseases. Analysis of multiple finger tapping (FT) parameters can contribute to identify the underlying physiopathology, while providing a quantitative clinical assessment tool, particularly in patients not reliably evaluated using clinical rating scales. Here, we used an automated method of FT analysis in Friedreich ataxia (FRDA) to disentangle cerebellar (prominent FT rate variability), extrapyramidal (FT progressive amplitude reduction without slowing of tapping rate), and pyramidal (progressive decrease of FT rate and amplitude) contribution to upper limb loss of dexterity. FT parameters were then related to FRDA clinical parameters and upper limbs motor evoked potential (MEPs). Twenty-four FRDA patients and matched healthy subjects performed FT with the dominant hand for 90 seconds. FT rate, FT rate variability, FT amplitude, and linear regressions of FT movement parameters were automatically computed. Eleven patients underwent MEPs, measured at the first dorsal interosseous of the dominant hand to determine central motor conduction time (CMCT). FRDA patients had slower and more regular FT rate than controls. Eleven FRDA patients showed FT rate slowing. Those patients had longer disease duration and higher Scale for the Assessment and Rating of Ataxia (SARA) scores. Seven patients with FT rate slowing had MEP and all displayed prolonged CMCT, whereas the 4 other patients with constant FT rate had normal CMCT. This study provides evidence for a prominent involvement of pyramidal dysfunction in upper limb dexterity loss as well as a potential outcome measure for clinical studies in FRDA.

Quantitative measurement of cartilage volume with automatic cartilage segmentation in knee osteoarthritis.

To determine the reproducibility of the automatic cartilage segmentation method using a prototype KneeCaP software (version 1.3; Siemens Healthcare, Erlangen, Germany) and to compare the difference in cartilage volume (CV) between the normal knee joint and knee osteoarthritis (KOA) of different degrees by using the above software. The study included 62 subjects with knee OA and 29 healthy control subjects. The cartilage lesion patients were divided into a mild-to-moderate OA group (n = 29) and severe OA group (n = 33). Automatic cartilage segmentation was performed on all the subjects, and among them, 19 knee cases were randomly selected to also do the manual cartilage segmentation. Statistical significance was determined with one-way analysis of variance (ANOVA), intraclass correlation coefficient (ICC), and Pearson correlation coefficient. Automatic segmentation was compared with the manual one. The relative cartilage volume percentages of the femur, tibia, and patella in the normal control/mild-to-moderate/severe OA groups were assessed. Comparing the cartilage volumes derived by manual and automatic segmentation, the ICC value for the knee joint, patella, femur, or tibia was 0.784, 0.815, 0.740, and 0.797. The relative cartilage volume percentages of the femur, tibia, and patella in the normal control/mild-to-moderate/severe OA groups were 57.28%/59.30%/62.45% (femur), 25.35%/23.46%/21.84% (tibia), and 17.37%/17.24%/15.71% (patella), respectively. Compared with the normal control group, the relative tibia cartilage volume percentage was lower in the mild-to-moderate OA group and the severe OA group. Corresponding index showed a similar difference between the mild-to-moderate OA group and the severe OA group (p < 0.001). This study demonstrated that the relative cartilage volume percentage is correlated with the semi-quantitative systems and may be a preferred outcome measure in clinical studies of OA. Automatic cartilage segmentation using KneeCaP delivered reliable results on high-spatial-resolution 3 T MR images for the healthy, mild-moderate OA patients. Key Points • The cartilage automatic segmentation has excellent reproducibility and was not affected by inter-observer variation. • The relative cartilage volume percentage is correlated with the semi-quantitative systems and may be a preferred outcome measure in clinical studies of OA.

Use of the Cutaneous Lupus Disease Area and Severity Index as an outcome measure in clinical trials: a descriptive study.

This study summarizes the use, since its inception, of the Cutaneous Lupus Disease Area and Severity Index (CLASI) as an outcome measure in clinical studies. We systematically searched the MEDLINE, PubMed, EMBASE and Cochrane databases for papers including the term 'cutaneous lupus disease area and severity index' and its abbreviations up to August 2017, identifying 205 abstracts. Following shortlisting, two independent physicians critically reviewed 71 papers for data extraction. We found that a limited number of high-quality studies used the CLASI scoring as an outcome measure. We concluded that further validation is necessary to identify the effectiveness of the CLASI in the assessment of cutaneous lupus erythematosus subtypes. The use of standardized core patient- and physician-reported outcome measures may reduce heterogeneity and allow comparisons between patients enrolled in clinical trials. This would improve the relevance within clinical practice, where the use of CLASI is currently limited.

Measuring What Matters to Individuals with Angelman Syndrome and Their Families: Development of a Patient-Centered Disease Concept Model

Angelman syndrome (AS) is a complex, heterogeneous, and life-long neurodevelopmental disorder. Despite the considerable impact on individuals and caregivers, no disease-modifying treatments are available. To support holistic clinical management and the development of AS-specific outcome measures for clinical studies, we conducted primary and secondary research identifying the impact of symptoms on individuals with AS and their unmet need. This qualitative research adopted a rigorous step-wise approach, aggregating information from published literature, then evaluating it via disease concept elicitation interviews with clinical experts and caregivers. We found that the AS-defining concepts most relevant for treatment included: impaired expressive communication, seizures, maladaptive behavior, cognitive impairment, motor function difficulties, sleep disturbance, and limited self-care abilities. We highlight the relevance of age in experiencing these key AS concepts, and the difference between the perceptions of clinicians and caregivers towards the syndrome. Finally, we outline the impact of AS on individuals, caregivers, and families.

Virtual reality in spinal endoscopy: a paradigm shift in education to support spine surgeons.

Minimally invasive spine surgery (MISS) and endoscopic spine surgery have continually evolving indications in the cervical, thoracic, and lumbar spine. Endoscopic spine surgery entails treatment of disc disease, stenosis, spondylolisthesis, radiculopathy, and deformity. MISS involves complex motor skills in regions of variable anatomy. Simulator use has been proposed to aid in training and skill retention, preoperative planning, and intraoperative use. A systematic review of five databases was performed for publications pertaining to the use of virtual (VR), augmented (AR), and mixed (MR) reality in MISS and spinal endoscopic surgery. Qualitative data analysis was undertaken with focus of study design, quality, and reported outcomes. Study quality was assessed using the Medical Education Research Quality Instrument (MERSQI) score and level of evidence (LoE) by a modified Oxford Centre for Evidence-Based Medicine (OCEBM) level for simulation in medicine. Thirty-eight studies were retained for data collection. Studies were of intervention-control, clinical application, and pilot or cross-sectional design. Identified articles illustrated use of VR, AR, and MR in all study designs. Procedures included pedicle cannulation and screw insertion, vertebroplasty, kyphoplasty, percutaneous transforaminal endoscopic discectomy (PTED), lumbar puncture and facet injection, transvertebral anterior cervical foraminotomy (TVACF) and posterior cervical laminoforaminotomy. Overall MERSQI score was low-to-medium [M =9.71 (SD =2.60); range, 4.5-13.5], and LoE was predominantly low given the number of purely descriptive articles, or low-quality randomized studies. The current scope of VR, AR, and MR surgical simulators in MISS and spinal endoscopic surgery was described. Studies demonstrate improvement in technical skill and patient outcomes in short term follow-up. Despite this, overall study quality and levels of evidence remain low. Cohesive study design and reporting with focus on transfer validity in training scenarios, and patient derived outcome measures in clinical studies are required to further advance the field.

PNS394 DEVELOPMENT OF A MULTIPLICATIVE MULTI-ATTRIBUTE AND SINGLE-ATTRIBUTE UTILITY FUNCTION FOR THE HUI3 IN JAPAN

The Health Utilities Index Mark 3 (HUI3) is a generic multiattribute preference-based measure of health status and health-related quality of life that is widely used as an outcome measure in clinical studies, in population health surveys, in the estimation of quality-adjusted life years. We aimed to present a multi-attribute utility function and eight single-attribute utility functions for the HUI3 system based on community preferences in Japan. Two preference surveys were conducted. One, the modeling survey, collected preference scores for the estimation of the utility functions. The other, the direct survey, provided independent scores to assess the predictive validity of the utility functions. Preference measures included value scores obtained on the Feeling Thermometer and standard gamble utility scores obtained using the Chance Board. We recruited 1,043 respondents (aged 20–79) from the general population, stratified by gender and age group, from five Japanese cities. Estimates were obtained for eight single-attribute utility functions and an overall multi-attribute utility function (MAUF). The Japanese HUI3 MAUF is u=1.016*(b1*b2*b3*b4*b5*b6*b7*b8)-0.016. The minimum predicted multi-attribute utility score was -0.002. The intraclass correlation coefficient between directly measured utility scores and scores generated by the multi-attribute function for 53 health states was 0.742. The HUI3 scoring function was developed in Japan has strong theoretical and empirical foundations. It seems to perform well in predicting directly measured scores for health technology assessment in Japan.

Invasive Respiratory or Vasopressor Support and/or Death as a Proposed Composite Outcome Measure for Perioperative Care Research.

There is a need for a clinically relevant and feasible outcome measure to facilitate clinical studies in perioperative care medicine. This large-scale retrospective cohort study proposed a novel composite outcome measure comprising invasive respiratory or vasopressor support (IRVS) and death. We described the prevalence of IRVS in patients undergoing major abdominal surgery and assessed the validity of combining IRVS and death to form a composite outcome measure. We retrospectively collected perioperative data for 2776 patients undergoing major abdominal surgery (liver, colorectal, gastric, pancreatic, or esophageal resection) at Kyoto University Hospital. We defined IRVS as requirement for mechanical ventilation for ≥24 hours postoperatively, postoperative reintubation, or postoperative vasopressor administration. We evaluated the prevalence of IRVS within 30 postoperative days and examined the association between IRVS and subsequent clinical outcomes. The primary outcome of interest was long-term survival. Multivariable Cox proportional regression analysis was performed to adjust for the baseline patient and operative characteristics. The secondary outcomes were length of hospital stay and hospital mortality. In total, 85 patients (3.1%) received IRVS within 30 postoperative days, 15 of whom died by day 30. Patients with IRVS had a lower long-term survival rate (1- and 3-year survival probabilities, 66.1% and 48.5% vs 95.2% and 84.0%, respectively; P < .001, log-rank test) compared to those without IRVS. IRVS was significantly associated with lower long-term survival after adjustment for the baseline patient and operative characteristics (adjusted hazard ratio, 2.72; 95% confidence interval, 1.97-3.77; P < .001). IRVS was associated with a longer hospital stay (median [interquartile range], 65 [39-326] vs 15 [12-24] days; adjusted P < .001) and a higher hospital mortality (24.7% vs 0.5%; adjusted P < .001). Moreover, IRVS was adversely associated with subsequent clinical outcomes including lower long-term survival (adjusted hazard ratio, 1.78; 95% confidence interval, 1.21-2.63; P = .004) when the analyses were restricted to 30-day survivors. Patients with IRVS can experience ongoing risk of serious morbidity and less long-term survival even if alive at postoperative day 30. Our findings support the validity of using IRVS and/or death as a composite outcome measure for clinical studies in perioperative care medicine.

Correction to: It is time for an organised, scientific approach to the application of patient-reported outcome measures in clinical studies and trials.

In the above article [1], the section labelled 'Misuse of the ASQoL' incorrectly lists Reference 19 [2] as having used an unauthorized language version of the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL).].

Sensor-based gait analysis of individualized improvement during apomorphine titration in Parkinson's disease.

Mobile, sensor-based gait analysis in Parkinson's disease (PD) facilitates the objective measurement of gait parameters in cross-sectional studies. Besides becoming outcome measures for clinical studies, the application of gait parameters in personalized clinical decision support is limited. Therefore, the aim of this study was to evaluate whether the individual response of PD patients to dopaminergic treatment may be measured by sensor-based gait analysis. 13 PD patients received apomorphine every 15min to incrementally increase the bioavailable apomorphine dose. Motor performance (UPDRS III) was assessed 10min after each apomorphine injection. Gait parameters were obtained after each UPDRS III rating from a 2×10m gait sequence, providing 41.2 ± 9.2 strides per patient and injection. Gait parameters and UPDRS III ratings were compared cross-sectionally after apomorphine titration, and more importantly between consecutive injections for each patient individually. For the individual response, the effect size Cohen's d for gait parameter changes was calculated based on the stride variations of each gait sequence after each injection. Cross-sectionally, apomorphine improved stride speed, length, gait velocity, maximum toe clearance, and toe off angle. Between injections, the effect size for individual changes in stride speed, length, and maximum toe clearance correlated to the motor improvement in each patient. In addition, significant changes of stride length between injections were significantly associated with UPDRS III improvements. We therefore show, that sensor-based gait analysis provides objective gait parameters that support clinical assessment of individual PD patients during dopaminergic treatment. We propose clinically relevant instrumented gait parameters for treatment studies and especially clinical care.

Swallowing markers in spinal and bulbar muscular atrophy.

ObjectiveWe examined the characteristics of dysphagia in spinal and bulbar muscular atrophy, a hereditary neuromuscular disease causing weakness of limb, facial, and oropharyngeal muscles via a videofluoroscopic swallowing study, and investigated the plausibility of using these outcome measures for quantitative analysis.MethodsA videofluoroscopic swallowing study was performed on 111 consecutive patients with genetically confirmed spinal and bulbar muscular atrophy and 53 age‐ and sex‐matched healthy controls. Swallowing of 3‐mL liquid barium was analyzed by the Logemann's Videofluorographic Examination of Swallowing worksheet.ResultsOf more than 40 radiographic findings, the most pertinent abnormal findings in patients with spinal and bulbar muscular atrophy, included vallecular residue after swallow (residue just behind the tongue base), nasal penetration, and insufficient tongue movement (P < 0.001 for each) compared with healthy controls. Quantitative analyses showed that pharyngeal residue after initial swallowing, oral residue after initial swallowing, multiple swallowing sessions, and the penetration–aspiration scale were significantly worse in these patients (P ≤ 0.005 for each) than in controls. In patients with spinal and bulbar muscular atrophy, laryngeal penetration was observed more frequently in those without subjective dysphagia.InterpretationDysphagia of spinal and bulbar muscular atrophy was characterized by impaired tongue movement in the oral phase and nasal penetration followed by pharyngeal residues, which resulted in multiple swallowing sessions and laryngeal penetration. Although major limitations of reproducibility and radiation exposure still exist with videofluoroscopy, pharyngeal residue after initial swallowing and the penetration–aspiration scale might serve as potential outcome measures in clinical studies.