Clinical Outcome Measures Research Articles

Dupliumab therapy for alopecia areata: a case series and review of the literature

Background A growing body of research supports the important role of the TH2 axis in alopecia areata (AA). Dupilumab is a humanized monoclonal antibody against IL-4Rα that downregulates TH2 response. Although efficacy has been shown in clinical trials, real-world data on the use of dupilumab in AA patients is limited. Objectives To report on a case series of 10 patients with AA who were treated with dupilumab and provide real-world evidence regarding its efficacy in treating severe AA. Methods In this retrospective single-center study, all AA patients treated with dupilumab treatment were included between May 2022 and October 2023. Clinical outcome measures (Severity of Alopecia Tool, SALT) and adverse events (AEs) were analyzed. In addition, a literature review was conducted to summarize the efficacy of AA with dupilumab and the characteristics of patients previously reported in the literature. Results We identified 10 patients with AA who were or are being treated with dupilumab, with a median (range) treatment duration of 8 (3-15) months. Of these, four patients have high serum immunoglobulin E (IgE) levels (≥200IU/ml). The mean (IQR) pretreatment SALT score was 79% (52-100). Seven of 10 patients achieved at least 50% re-growth. Of those who improved, the mean (IQR) percentage change in SALT score at 3 months and the end of follow-up was 57% (29%-89%) and 95% (68-100), respectively. Notably, seven patients (70%) had white hair regrowth, with the white hair slowly decreasing over time and the proportion of pigmented black hair increasing. Dupilumab was well tolerated by all patients. No adverse events were reported. Conclusions Overall, our research supports dupilumab as another candidate that possesses potential benefits for AA. High levels of IgE may be not prerequisites for dupilumab’s successful treatment response.

Senescence marker p16INK4a expression in patients with multiple sclerosis

ObjectivesTelomere attrition is associated with disability accumulation and brain atrophy in multiple sclerosis (MS). Downstream of telomere attrition is cellular senescence. We sought to determine differences in the cellular senescence marker p16INK4a expression between MS and healthy control participants and the association of p16INK4a expression with MS disability and treatment exposure. MethodsPatients meeting diagnostic criteria for MS and healthy controls were recruited for a cross-sectional pilot study. RNA was extracted from peripheral blood mononuclear cells (PBMCs) and p16INK4a expression levels were measured using qRT PCR. Spearman correlation coefficients and regression models were applied to compare expression levels to chronological age, assess case control differences, and determine associations with clinical outcome measures. ResultsFifty-two participants with MS (67 % female, ages 25–70) and 38 healthy controls (66 % female, ages 23–65) were included. p16INK4a levels were not linearly correlated with chronological age in MS (rhos = −0.01, p = 0.94) or control participants (rhos = 0.02, p = 0.92). Higher median p16INK4a levels were observed in the >50-year age group for MS (0.25, IQR 0.14–0.35) vs. controls (0.12, IQR 0.05–0.15) and in this age group B cell depletion therapy was associated with lower expression levels. p16INK4a expression was not associated with any of the measured MS disability outcomes. DiscussionCaution is needed with using p16INK4a expression level from PBMCs as an aging biomarker in MS participants, given lack of correlation with chronological age or large associations with clinical outcomes.

Investigation of the Impact of Wellinks on the Quality of Life and Clinical Outcomes in Patients With Chronic Obstructive Pulmonary Disease: Interventional Research Study.

Wellinks is a remote disease management solution that provides novel chronic obstructive pulmonary disease (COPD) care delivery. This study evaluated the satisfaction, engagement, and clinical outcomes of Wellinks participants. This study also investigated the cadence of health coaching for patients with COPD. A 24-week interventional study was conducted by Wellinks and the COPD Foundation in 2022. Adults with COPD were recruited by the COPD Foundation in the United States and determined to be eligible if they had phone and internet access, owned a smartphone, and were not currently participating in pulmonary rehabilitation. All study participants provided written informed consent. The Wellinks solution included remote health coaching, pulmonary rehabilitation, and group education; participants were provided the Wellinks app and smart spirometry and pulse oximetry devices. Participants were offered 6 coaching sessions in the first 12 weeks. For the second 12-week period, participants either reduced frequency or discontinued coaching; all other components of the Wellinks solution remained unchanged. The COPD Self-Efficacy Scale, Modified Medical Research Council dyspnea scale, pulmonary function, pulse oximetry, and patient-reported healthcare resource utilization were the clinical outcome measures. Nonclinical outcomes included engagement and satisfaction with Wellinks and net promoter score. In total, 141 adults consented and completed Wellinks onboarding; 84.4% (n=119) of whom remained engaged throughout the 24-week study. Participants had a mean age of 70 (SD 7.8; range 48-88) years, and 55.7% (n=78) were female. Most participants (n=119, 84.4%) completed all 6 coaching sessions during the first 12-week period. Compliance with spirometer and pulse oximeter use was 82.3% and 89.4%, respectively, at week 1 but waned over the study period to 8.5% and 9.2%, respectively, at the end of the study. Participants indicated a high degree of satisfaction with Wellinks, with 95.5% (n=85) and 91% (n=81) of participants indicating that they agreed or strongly agreed that the educational content and health coaching, respectively, were valuable. At the end of the study, the net promoter score was +64 and +55 in the coaching continuation and discontinuation arms, respectively. A significant improvement from baseline to end of the study was observed in the COPD Self-Efficacy Scale total score (P<.001) and domain scores (P<.001 for each domain). In total, 35.1% (n=27) of participants improved by at least 1 category of change on the 5-point Modified Medical Research Council dyspnea scale from baseline to week 24. This study confirmed the feasibility of using a remote model of care delivery to support people living with COPD. The insights gained in this study have allowed for further refinement and personalization of the Wellinks care model. Findings related to the combined use of technology and personal care delivery should be considered by others developing remote disease management tools. ClinicalTrials.gov NCT05259280; https://clinicaltrials.gov/ct2/show/NCT05259280.

Psychological risk factors predictive of suicidal distress in men receiving a community‐based brief psychological intervention

AbstractIntroductionAdaptable community‐based approaches for assessment and delivery of suicide prevention interventions for men experiencing suicidal crisis are needed. The lay your cards on the table (LYCT) component of the James' Place Model is a novel therapeutic approach comprised of four sets of card variables that correspond with suicidal risk factors. This study investigated the LYCT in predicting suicidal distress among men.MethodsCross‐sectional data of 511 men aged 18–69 years (M = 34.59 years; SD = 12.30) collected between 1st August 2018 and 29th July 2021 were assessed to predict suicidal distress measured using the CORE Clinical Outcome Measures (CORE‐OM).ResultsFrom four categories comprising the LYCT, correlational analyses demonstrated that 20 associations emerged as statistically significant (r's = 0.12–0.19). When these were included in regression analyses, effect sizes explained 2%–5% variance in CORE‐OM outcomes (R2).ConclusionUse of LYCT is supported for engaging men in the assessment of suicide risk factors and to inform tailoring of intervention delivery to suit the individual needs of men experiencing suicidal crisis.

NSF DARE—transforming modeling in neurorehabilitation: perspectives and opportunities from US funding agencies

In recognition of the importance and timeliness of computational models for accelerating progress in neurorehabilitation, the U.S. National Science Foundation (NSF) and the National Institutes of Health (NIH) sponsored a conference in March 2023 at the University of Southern California that drew global participation from engineers, scientists, clinicians, and trainees. This commentary highlights promising applications of computational models to understand neurorehabilitation (“Using computational models to understand complex mechanisms in neurorehabilitation” section), improve rehabilitation care in the context of digital twin frameworks (“Using computational models to improve delivery and implementation of rehabilitation care” section), and empower future interdisciplinary workforces to deliver higher-quality clinical care using computational models (“Using computational models in neurorehabilitation requires an interdisciplinary workforce” section). The authors describe near-term gaps and opportunities, all of which encourage interdisciplinary team science. Four major opportunities were identified including (1) deciphering the relationship between engineering figures of merit—a term commonly used by engineers to objectively quantify the performance of a device, system, method, or material relative to existing state of the art—and clinical outcome measures, (2) validating computational models from engineering and patient perspectives, (3) creating and curating datasets that are made publicly accessible, and (4) developing new transdisciplinary frameworks, theories, and models that incorporate the complexities of the nervous and musculoskeletal systems. This commentary summarizes U.S. funding opportunities by two Federal agencies that support computational research in neurorehabilitation. The NSF has funding programs that support high-risk/high-reward research proposals on computational methods in neurorehabilitation informed by theory- and data-driven approaches. The NIH supports the development of new interventions and therapies for a wide range of nervous system injuries and impairments informed by the field of computational modeling. The conference materials can be found at https://dare2023.usc.edu/.

Assessment of Platelet-Rich Plasma Alone and Platelet-Rich Plasma Combined with Bioactive Glass in the Management of Intrabony Defect

ABSTRACT Objectives: To assess the function of platelet-rich plasma (PRP) both only and in combination with bioactive glass in intrabony defects. Materials and Method: Twenty patients were split into two groups with 10 samples each: group I with PRP alone, whereas group II was done with PRP in addition to bioactive glass. Following local anesthesia, full-thickness mucoperiosteal flaps were elevated in the afflicted site, the defect was debrided, and root planning with curettes was performed. Irrigation was then used while in group II- PRP along with bone graft (BG) preservationwas done. Suturing in group I was contained. At day 0 (baseline) and 6 months after surgery, the clinical parameters for probing depth, clinical attachment stage, and radiographic assessment were noted for both groups. Result: When comparing both groups, there was no statistically considerable variation. However, the intragroup comparison for pocket depth and clinical attachment level between baseline and 6 months was significant. Radiographic bone level was not considerably dissimilar across groups; however, it was significantly different between groups Conclusion: Reduced probing depth, higher clinical attachment level, and radiographic evidence of bone fill are clinical outcome measures that are associated with effective regenerative therapy.

Collaborative care model versus usual care for the management of musculoskeletal and co-existing mental health conditions: a randomised feasibility mixed-methods study

ObjectiveThis study aimed to assess the feasibility of a future trial comparing the collaborative care model with usual care for patients with musculoskeletal conditions and co-existing symptoms of anxiety and...

Radiochemotherapy and interstitial brachytherapy for cervical cancer: clinical results and patient-reported outcome measures

ObjectiveTo evaluate clinical results and long-term patient-reported outcome measures (PROMs) on quality of life in cervical cancer patients following radiochemotherapy (RCT) and brachytherapy (BT) as definitive treatment.Materials and methodsBetween 2003 and 2023, a total of 132 patients with advanced cervical cancer were evaluated for possible treatment. Patients treated by postoperative RCT, palliative radiotherapy, and those treated for recurrent disease were excluded. Thus, 46 patients receiving standard RCT and BT as their curative treatment were included in this study. PROMs were assessed prospectively by patients’ self-completion of the EORTC-QLQ-C30 and EORTC-QLQ-CX24 questionnaires.ResultsFive-year overall survival (OS), distant metastases-free survival (DMFS), and pelvic tumor-free survival rates (PTFS) were 53%, 54%, and 83%, respectively. A significant impact on OS was seen for FIGO (International Federation of Gynecologic Oncology) stage (IIB–IIIA: 79% vs. IIIB–IVA: 33%, p = 0.015), for overall treatment time (OTT; 50–65 d: 64% vs. > 65 d: 38%, p = 0.004), and for rectal D2cc (≤ 73 Gy: 50% vs. > 73 Gy: 38%, p = 0.046). The identical parameters were significantly associated with DMFS (FIGO stage: p = 0.012, OTT: p = 0.008, D2cc: p = 0.024). No parameters with a significant influence on PTFS were seen. In multivariate analysis, an impact of FIGO stage on OS (p = 0.05) and DMFS (p = 0.014) was detected, and of rectal D2cc on DMFS (p = 0.031). The overall QoL score was 63/100. Cognitive function was the least impaired (84/100), while role functioning was the worst (67/100). On the symptom scale, insomnia (46/100), fatigue (41/100), dyspnea (32/100), pain (26/100), and financial difficulties (25/100) were scored the worst. According to EORTC-QLQ-CX24, peripheral neuropathy (36/100) and lymphedema (32/100) occurred most frequently. Impaired sexual/vaginal functioning (32/100) and body image (22/100) were also frequently recorded.ConclusionIn patients with advanced cervical cancer, a combination of RCT and BT remains an excellent treatment option. In terms of patient-reported long-term quality of life, specific support is needed to alleviate symptoms including lymphedema, peripheral neuropathy, and impaired sexual activity.

Percutaneous short segmental fixation combined with bone cement augmentation for stage III Kümmell's disease without nerve deformity.

The objective of this study was to evaluate the safety and efficacy of percutaneous pedicle screw fixation combined with bone cement augmentation in the management of stage III Kümmell disease without nerve deformity. A retrospective analysis was conducted on 17 patients diagnosed with stage III Kümmell disease without nerve deformity, who underwent treatment with percutaneous pedicle screw fixation combined with bone cement augmentation between April 2019 and 2022. Preoperative, postoperative, and final follow-up clinical outcome measures were collected, including Visual Analog Scale scores and Oswestry Disability Index scores. Additionally, lateral radiography was used to measure the Cobb angle and height of the anterior border of the affected vertebral body. Operative time, volume of injected bone cement, intraoperative cement leakage, and other complications were recorded. All patients underwent successful surgery, resulting in significant reductions in Visual Analog Scale scores, Oswestry Disability Index scores, and Cobb angle postoperatively; meanwhile there was a significant increase in height of the anterior border of the affected vertebral body. No major complications occurred during the follow-up period. In conclusion, percutaneous pedicle screw short-segment fixation combined with bone cement augmentation appears to be an effective surgical option for treating stage III Kümmell disease without nerve deformities.

Quantitative muscle ultrasound as a disease biomarker in hereditary transthyretin amyloidosis with polyneuropathy.

There is an increasing need for a reproducible and sensitive outcome measure in patients with hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy (PN) due to the emergence of disease modifying therapies. In the current study, we aimed to investigate the role of quantitative muscle ultrasound (QMUS) as a disease biomarker in ATTRv-PN. Twenty genetically confirmed ATTRv amyloidosis patients (nine symptomatic, 11 pre-symptomatic) were enrolled prospectively between January to March 2023. Muscle ultrasound was performed on six muscles at standardized locations. QMUS parameters included muscle thickness (MT) and muscle echo intensity (EI). Twenty-five age- and sex-matched healthy controls were recruited for comparison. Significant QMUS parameters were correlated with clinical outcome measures. Muscle volume of first dorsal interosseus (FDI) muscle [measured as cross-sectional area (CSA)] was significantly lower in symptomatic patients compared to healthy controls and pre-symptomatic carriers (98.3 ± 58.0 vs. 184.4 ± 42.5 vs. 198.3 ± 56.8, p < 0.001). EI of biceps and FDI for symptomatic ATTRv-PN patients were significantly higher compared to the other two groups (biceps: 76.4 ± 10.8 vs. 63.2 ± 11.5 vs. 59.2 ± 9.0, p = 0.002; FDI: 48.2 ± 7.5 vs. 38.8 ± 7.5 vs. 33.0 ± 5.3, p < 0.001). CSA of FDI and EI of biceps and FDI correlated with previous validated outcome measures [polyneuropathy disability score, neuropathy impairment score, Karnofsky performance scale, Rasch-built overall disability scale, European quality of life (QoL)-5 dimensions and Norfolk QoL questionnaire-diabetic neuropathy]. QMUS revealed significant difference between ATTRv amyloidosis patients and healthy controls and showed strong correlation with clinical outcome measures. QMUS serves as a sensitive and reliable biomarker of disease severity in ATTRv-PN.

Thresholds for unacceptable work state in radiographic axial Spondyloarthritis of four presenteeism and two clinical outcome measurement instruments.

To a) identify threshold values of presenteeism measurement instruments that reflect unacceptable work state in employed r-axSpA patients; b) determine whether those thresholds accurately predict future adverse work outcomes (AWO) (sick leave or short/long-term disability); c) evaluate the performance of traditional health-outcomes for r-axSpA; d) explore whether thresholds are stable across contextual factors. Data from the multinational AS-PROSE study was used. Thresholds to determine whether patients consider themselves in an 'unacceptable work state' were calculated at baseline for four instruments assessing presenteeism and two health-outcomes specific for r-axSpA. Different approaches derived from the receiver operating characteristic methodology were used. Validity of the optimal thresholds was tested across contextual factors and for predicting future AWO over 12 months. Of 366 working patients, 15% reported an unacceptable work state; 6% experienced at least one AWO in 12 months. Optimal thresholds were: WPAI-presenteeism ≥40 (AUC 0.85), QQ-method <97 (0.76), WALS ≥0.75 (AUC 0.87), WLQ-25 ≥ 29 (AUC 0.85). BASDAI and BASFI performed similarly to the presenteeism instruments: ≥4.7 (AUC 0.82) and ≥3.5 (AUC 0.79), respectively. Thresholds for WALS and WLQ-25 were stable across contextual factors, while for all other instruments they overestimated unacceptable work state in lower educated persons. Proposed thresholds could also predict future AWO, although with lower performance, especially for QQ-method, BASDAI and BASFI. Thresholds of measurement instruments for presenteeism and health status to identify unacceptable work state have been established. These thresholds can help in daily clinical practice to provide work related support to r-axSpA patients at risk for AWO.

P1013 Placebo rates in Crohn's disease: An individual patient data meta-analysis from multiple randomised controlled trials

Abstract Background Estimating placebo rates and their determinants is essential for designing efficient randomised clinical trials (RCTs) in inflammatory bowel disease. We conducted an individual patient data (IPD) meta-analysis of placebo data from RCTs in Crohn’s disease (CD). Methods MEDLINE, Embase, and CENTRAL were searched from 01/2010 to 01/2020 for contemporary phase 2 and 3 placebo-controlled RCTs of biologics in moderate-to-severe CD. De-identified IPD from eligible trials that were available through the Vivli and Yale University Open Data Access data-sharing platforms were obtained. Primary outcomes were placebo clinical response and remission. Pooled placebo rates and 95% CIs were estimated using a 2-stage meta-analytical approach. Significant patient-level factors (P&amp;lt;0.05) associated with placebo rates were identified using regression analyses. Results Placebo IPD were available from 8 induction (n=1147) and 4 maintenance trials (n=524). Pooled placebo clinical response and remission rates varied based on outcome definition and prior biologic exposure (Figure). In induction trials, overall placebo response and remission rates were 27% (95% CI 23-32%) and 10% (95% CI 8-14%), respectively. Among bio-exposed patients, placebo response and remission rates were 27% (95% CI 16-40%) and 9% (95% CI 6-15%), respectively, compared with 29% (95% CI 24-34%) and 11% (95% CI 8-15%) for bio-naïve patients. Overall placebo response and remission rates in maintenance trials were 32% (95% CI 23%-42%) and 22% (95% CI 14-33%), respectively. Corresponding placebo response and remission rates for bio-exposed patients were 21% (95% CI 8-46%) and 17% (95% CI 11-25%), and 36% (95% CI 28-44%) and 24% (95% CI 15-36%) for bio-naïve patients. Placebo rates were lowest when response was defined as a ≥100-point decrease from baseline in the Crohn's Disease Activity Index (CDAI) score, and when remission was defined using stool frequency (≤1.5) and abdominal pain (≤1) subscores. Higher baseline C-reactive protein concentrations were associated with lower odds of placebo response and remission, while higher baseline albumin levels increased the odds of these outcomes (Table). Increased baseline CDAI and 2-item patient-reported outcome (PRO2) scores predicted higher odds of placebo response in induction trials, yet this reduced the odds of remission in induction trials and of both outcomes in maintenance trials. Prior failure to tumour necrosis factor (TNF) antagonist therapy was more predictive than prior TNF antagonist/biologic exposure for reducing the odds of placebo response and remission. Conclusion Placebo rates and the patient-level factors influencing them vary according to study design, clinical outcome measure and outcome definitions.

P348 Increased pre-treatment faecal calprotectin concentration predicts resistance to ustekinumab induction in ulcerative colitis

Abstract Background Rates of resistance to advanced therapy remain high in ulcerative colitis (UC). Pre-treatment predictors of poor outcomes would provide valuable information for treating clinicians so other therapies could be given or early treatment switches could be considered if response is inadequate. We investigated whether baseline, pre-treatment faecal calprotectin (FCP) can predict resistance to ustekinumab. Methods Clinical outcomes at week 8, including clinical remission, endoscopic healing and mucosal healing were determined in patients enrolled in the UNIFI phase 3 placebo-controlled trial program, investigating the efficacy of ustekinumab for moderate-to-severe UC (GSE206285), in whom FCP concentrations were available at baseline, prior to initiation of treatment. Clinical outcomes were defined in patients with FCP &amp;lt; 250mcg/g, 250 – 999mcg/g, 1000 – 1999mcg/g and &amp;gt;= 2000mcg/g. Chi-squared test was used to assess statistical significance. Area under the receiver operating characteristics curve (AUROC) analyses were used to determine the ability of faecal calprotectin level to predict treatment resistance. Analyses were performed using R 4.2.3 (Vienna, Austria) and GraphPad Prism 10.0.3 (Massachusetts, United States). Results Outcome data and linked faecal calprotectin levels were available for 340 patients. FCP values ranged from 15 – 25249mcg/g. The median FCP value was 1402mcg/g (interquartile range: 600.8 – 2772.0mcg/g). In general, all clinical outcome measures were progressively worse with increasing FCP concentrations. For the respective FCP cut-offs, 22.0%, 19.3%, 11.3% and 6.7% achieved clinical remission; 39.0%, 24.1%, 20.6% and 16.0% achieved endoscopic healing; and 29.3%, 16.9%, 15.5% and 7.6% achieved mucosal healing (Figure 1). ROC analyses revealed that pre-treatment FCP predicts resistance to ustekinumab therapy for all stated outcomes, including clinical remission (AUROC: 0.66, P=0.001), endoscopic healing (AUROC: 0.63, P=0.0013) and mucosal healing (AUROC: 0.65, P=0.0005). Conclusion Increasing concentrations of pre-treatment FCP predicts resistance to ustekinumab therapy in moderate-to-severe UC. Patients with FCP &amp;gt;= 2000mcg/g were significantly less likely than those with FCP &amp;lt;1000 mcg/g to achieve clinical remission or mucosal healing. Since neutrophils are the main producers of FCP, these data build on other emerging data indicating that excessive accumulation of mucosal neutrophils is associated with treatment resistance in IBD.

Defining quality indicators, pharmaceutical care bundles and outcomes of clinical pharmacy service delivery using a Delphi consensus approach.

Clinical pharmacy quality indicators are often non-uniform and measure individual activities not linked to outcomes. To define a consensus agreed pharmaceutical care bundle and patient outcome measures across an entire state health service. A four-round modified-Delphi approach with state Directors of Pharmacy was performed (n = 25). They were asked to rate on a 5-point Likert scale the relevance and measurability of 32 inpatient clinical pharmacy quality indicators and outcome measures. They also ranked clinical pharmacy activities in order from perceived most to least beneficial. Based upon these results, pharmaceutical care bundles consisting of multiple clinical pharmacy activities were formed, and relevance and measurability assessed. Response rate ranged from 40 to 60%. Twenty-six individual clinical pharmacy quality indicators reached consensus. The top ranked clinical pharmacy quality indicator was 'proportion of patients where a pharmacist documents an accurate list of medicines during admission'. There were nine pharmaceutical care bundles formed consisting between 3 and 7 activities. Only one pharmaceutical care bundle reached consensus: medication history, adverse drug reaction/allergy documentation, admission and discharge medication reconciliation, medication review, provision of medicines education and provision of a medication list on discharge. Sixteen outcome measures reached consensus. The top ranked were hospital acquired complications, readmission due to medication misadventure and unplanned readmission within 10 days. Consensus has been reached on one pharmaceutical care bundle and sixteen outcomes to monitor clinical pharmacy service delivery. The next step is to measure the extent of pharmaceutical care bundle delivery and the link to patient outcomes.

Spatial normalization for voxel-based lesion symptom mapping: impact of registration approaches.

Voxel-based lesion symptom mapping (VLSM) assesses the relation of lesion location at a voxel level with a specific clinical or functional outcome measure at a population level. Spatial normalization, that is, mapping the patient images into an atlas coordinate system, is an essential pre-processing step of VLSM. However, no consensus exists on the optimal registration approach to compute the transformation nor are downstream effects on VLSM statistics explored. In this work, we evaluate four registration approaches commonly used in VLSM pipelines: affine (AR), nonlinear (NLR), nonlinear with cost function masking (CFM), and enantiomorphic registration (ENR). The evaluation is based on a standard VLSM scenario: the analysis of statistical relations of brain voxels and regions in imaging data acquired early after stroke onset with follow-up modified Rankin Scale (mRS) values. Fluid-attenuated inversion recovery (FLAIR) MRI data from 122 acute ischemic stroke patients acquired between 2 and 3 days after stroke onset and corresponding lesion segmentations, and 30 days mRS values from a European multicenter stroke imaging study (I-KNOW) were available and used in this study. The relation of the voxel location with follow-up mRS was assessed by uni- as well as multi-variate statistical testing based on the lesion segmentations registered using the four different methods (AR, NLR, CFM, ENR; implementation based on the ANTs toolkit). The brain areas evaluated as important for follow-up mRS were largely consistent across the registration approaches. However, NLR, CFM, and ENR led to distortions in the patient images after the corresponding nonlinear transformations were applied. In addition, local structures (for instance the lateral ventricles) and adjacent brain areas remained insufficiently aligned with corresponding atlas structures even after nonlinear registration. For VLSM study designs and imaging data similar to the present work, an additional benefit of nonlinear registration variants for spatial normalization seems questionable. Related distortions in the normalized images lead to uncertainties in the VLSM analyses and may offset the theoretical benefits of nonlinear registration.

Decreasing the incidence of delirium via multi-sensory stimulation in patients receiving mechanical ventilation in the intensive care unit: A protocol for a randomized feasibility study

IntroductionDelirium is a common acute brain dysfunction syndrome in patients admitted to intensive care units (ICUs). Family engagement strategies, based on the theory of multi-sensory stimulation to ameliorate sensory deprivation in patients, may be an effective and scalable method to reduce the burden of delirium. Methods/design: This is a assessor-blinded, randomised controlled trial of the feasibility of multi-sensory stimulation (MS) in patients with delirium. A total of 72 mechanically ventilated patients (n = 24 in each group) admitted to the ICU will be randomised to routine non-pharmacological delirium care (control), family multi-sensory stimulation and nurse multi-sensory stimulation groups. All participants except the control group will receive multi-sensory stimulation, including visual, auditory, tactile and kinesthetic stimulation, for 5 days. Our primary aim is to determine the feasibility of the study procedure (recruitment, eligibility, retention and attrition rates, appropriateness of clinical outcome measures), feasibility, acceptability and safety of the intervention (adverse events, satisfaction and other). Our secondary objective is to assess the preliminary efficacy of the MS protocol in reducing the incidence, duration and severity of delirium. Sedation levels and delirium severity will be assessed twice daily. Enrolled participants will be followed in hospital until death, discharge or up to 28 days after treatment. Ethics and disseminationThe current study was approved by the Ethics Review Board of Huazhong University of Science and Technology Union Shenzhen Hospital, China (KY-2023-031-01). The results of this study will be presented at scientific conferences and submitted for publication in peer-reviewed journals. Trial registration numberChiCTR2300071457.

Evaluation and recommendations of the oral health, oral function, and orofacial aesthetics-related measures of the ICHOM Standard Set for Cleft Lip and Palate

This study was performed to evaluate the efficacy of outcome measures for the orofacial domain included in the International Consortium for Health Outcomes Measurement Standard Set for Cleft Lip and Palate (ICHOM-SCS). In this multicentre study involving two cleft centres, suggestions to optimize the type and timing of outcome measures were made based on data and clinical experience. Patient-reported outcome measures (PROMs) (CLEFT-Q Jaw, Teeth, Eating/Drinking; Child Oral Health Impact Profile—Oral Symptoms Scale (COHIP-OSS)) and clinical outcome measures (caries experience and dental occlusion) data were collected retrospectively for age 5, 8, 10, 12, 19, and 22 years. The data were categorized by cleft type and analysed within and between age groups using Spearman correlation, the distribution of responses per item, a two-sample test for equality of proportions, and effect plots. Most correlations between PROMs and clinical outcome measures were weak (r < 0.5), suggesting PROMs and clinical outcome measures complement each other. The COHIP-OSS and CLEFT-Q Eating/Drinking barely detected problems in any patient category and are no longer recommended. A suitable alternative appears complex to find; outcomes of this study and the recent literature doubt an added value. Similar problems were found in the CLEFT-Q Jaw at time-point 12 years. Therefore, time-points 15 and 17 years are currently suggested.

Clinical Outcome Measures in Addiction Psychiatry

Background and Aims Several outcome measures have been utilized in addiction psychiatry. This paper discusses the various aspects of consideration for utilization and critical scrutiny of outcome measures used for various purposes in addiction psychiatry. Methods We followed a narrative review methodology to describe the various facets of outcome measures used, including the types of outcome measures, target respondents, validity, and applicability of the outcome measures. Results Varied forms of outcome measures have been used in addiction psychiatry, which can be schematically divided into substance use frequency and/or amount, the impact of substance use on functioning, quality of life, broad functioning measures, costs incurred on substance use, recovery capital, and recovery, composite directed measures self-report, diagnostic instruments, ecological momentary assessment, biochemical verification, and other ancillary outcomes. Each of the methods has its own strengths and contextual utility. One would also need to consider cultural aspects and purported utility while planning and implementing outcome measures. Conclusion Outcome measures have an important role in demonstrating effect and facilitating comparisons in addiction psychiatry, both in clinical trials and non-trial situations. Careful considerations for choosing outcome measures would enhance their utility.

Error Enhancement for Upper Limb Rehabilitation in the Chronic Phase after Stroke: A 5-Day Pre-Post Intervention Study.

A large proportion of chronic stroke survivors still struggle with upper limb (UL) problems in daily activities, typically reaching tasks. During three-dimensional reaching movements, the deXtreme robot offers error enhancement forces. Error enhancement aims to improve the quality of movement. We investigated clinical and patient-reported outcomes and assessed the quality of movement before and after a 5 h error enhancement training with the deXtreme robot. This pilot study had a pre-post intervention design, recruiting 22 patients (mean age: 57 years, mean days post-stroke: 1571, male/female: 12/10) in the chronic phase post-stroke with UL motor impairments. Patients received 1 h robot treatment for five days and were assessed at baseline and after training, collecting (1) clinical, (2) patient-reported, and (3) kinematic (KINARM, BKIN Technologies Ltd., Kingston, ON, Canada) outcome measures. Our analysis revealed significant improvements (median improvement (Q1-Q3)) in (1) UL Fugl-Meyer assessment (1.0 (0.8-3.0), p < 0.001) and action research arm test (2.0 (0.8-2.0), p < 0.001); (2) motor activity log, amount of use (0.1 (0.0-0.3), p < 0.001) and quality of use (0.1 (0.1-0.5), p < 0.001) subscale; (3) KINARM-evaluated position sense (-0.45 (-0.81-0.09), p = 0.030) after training. These findings provide insight into clinical self-reported and kinematic improvements in UL functioning after five hours of error enhancement UL training.

Technique and impact on first pass effect primary results of the ASSIST global registry

BackgroundPatients treated with mechanical thrombectomy (MT) for acute ischemic strokes from large vessel occlusion (LVO) have better outcomes with effective reperfusion. However, it is unknown which technique leads to better...