Pharmacovariome scanning using whole pharmacogene resequencing coupled with deep computational analysis and machine learning for clinical pharmacogenomics.

BACKGROUND: This pilot study aims to identify and functionally assess pharmacovariants in whole exome sequencing data. While detection of known variants has benefited from pharmacogenomic-dedicated bioinformatics tools before, in this paper we have tested novel deep computational analysis in addition to artificial intelligence as possible approaches for functional analysis of unknown markers within less studied drug-related genes. METHODS: Pharmacovariants from 1800 drug-related genes from 100 WES data files underwent (a) deep computational analysis by eight bioinformatic algorithms (overall containing 23 tools) and (b) random forest (RF) classifier as the machine learning (ML) approach separately. ML model efficiency was calculated by internal and external cross-validation during recursive feature elimination. Protein modelling was also performed for predicted highly damaging variants with lower frequencies. Genotype-phenotype correlations were implemented for top selected variants in terms of highest possibility of being damaging. RESULTS: Five deleterious pharmacovariants in the RYR1, POLG, ANXA11, CCNH, and CDH23 genes identified in step (a) and subsequent analysis displayed high impact on drug-related phenotypes. Also, the utilization of recursive feature elimination achieved a subset of 175 malfunction pharmacovariants in 135 drug-related genes that were used by the RF model with fivefold internal cross-validation, resulting in an area under the curve of 0.9736842 with an average accuracy of 0.9818 (95% CI: 0.89, 0.99) on predicting whether a carrying individuals will develop adverse drug reactions or not. However, the external cross-validation of the same model indicated a possible false positive result when dealing with a low number of observations, as only 60 important variants in 49 genes were displayed, giving an AUC of 0.5384848 with an average accuracy of 0.9512 (95% CI: 0.83, 0.99). CONCLUSION: While there are some technologies for functionally assess not-interpreted pharmacovariants, there is still an essential need for the development of tools, methods, and algorithms which are able to provide a functional prediction for every single pharmacovariant in both large-scale datasets and small cohorts. Our approaches may bring new insights for choosing the right computational assessment algorithms out of high throughput DNA sequencing data from small cohorts to be used for personalized drug therapy implementation.

A Review of Meaningful Change Thresholds for EORTC QLQ-C30 and FACT-G Within Oncology.

OBJECTIVES: This literature review provides an overview of meaningful change thresholds for the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) and the Functional Assessment of Cancer Therapy - General (FACT-G) used across hematological cancers and solid tumors (melanoma, lung, bladder, and prostate). METHODS: Embase, MEDLINE, and PubMed were searched to identify relevant oncology publications from 2016 to 2021. Label claims from the US Food and Drug Administration and the European Medicines Agency for 7 recently approved drugs (pembrolizumab, atezolizumab, glasdegib, gilteritinib, tisagenlecleucel, axicabtagene ciloleucel, and daratumumab plus hyaluronidase-fihj) were reviewed. RESULTS: Publications providing guidance on meaningful change thresholds for the QLQ-C30 displayed a growing trend away from broad "legacy" thresholds of 10 points for all QLQ-C30 scales), toward deriving "contemporary" thresholds (eg, subscale specific, population specific). Contemporary publications generally provide guidance on selecting thresholds for specific scales that account for improved or worsening thresholds (eg, QLQ-C30 subscales). This trend was not clear for FACT-G, with less new guidance available. Most clinical trials used in regulatory label submissions have used thresholds of 10 points for the QLQ-C30 subscales and 3 to 7 points for the FACT-G total score. Despite the availability of more recent guidelines, contemporary meaningful change thresholds seem slow to emerge in the published literature and regulatory labels. CONCLUSIONS: Trialists should consider using contemporary thresholds, rather than legacy thresholds, for QLQ-C30 endpoints. Thresholds derived for a similar patient-population should be used where available. Further work is required to provide these across a broader range of cancer sites.

Health-related quality of life in ethnically diverse Black prostate cancer survivors: a convergent parallel mixed-methods approach.

PURPOSE: This study examined the health-related quality of life (HRQoL) among ethnically diverse Black men (BM) with prostate cancer (CaP) in the United States. METHODS: A convergent parallel mixed-methods design, employing both qualitative and quantitative research, involved recruiting Black CaP survivors through multiple channels. The target population was native-born BM (NBBM), African-born BM (ABBM), and Caribbean-born BM (CBBM). QoL for all men was assessed using The Functional Assessment Cancer Therapy-Prostate (FACT-P) measure, which includes five domains: physical- (PWB), emotional- (EWB), social-(SWB), and functional-wellbeing (FWB), and a CaP subscale (PCS). A subset of men completed qualitative interviews. Demographic and clinical characteristics were also collected. RESULTS: Black CaP survivors aged 49-85 participated in the study (n = 108), with a subset (n = 31) completing a qualitative interview. Participants were mainly NBBM (72.2%) and treated with radiotherapy (51.9%). The FACT-P scale total mean score (± SD) was 114 ± 24.1 (theoretical range 0-156), with lower scores reported on the SWB, FWB, and EWB domains. The mixed-methods findings approach included meta-inferences derived from integrating the corresponding quantitative and qualitative data, covering all the domains within the FACT-P. CONCLUSION: Black CaP survivors experienced significant burdens that impacted their overall HRQoL. The analysis revealed impacts on physical, social, and emotional well-being, with variations among ethnic groups suggesting the need for culturally tailored interventions. EWB was also profoundly impacted by CaP treatment, with universal emotional burdens emphasized across all groups. Healthcare providers must recognize and address these multifaceted needs to promote better outcomes and HRQoL for Black CaP survivors.

Identification and functional characteristics of CHD1L gene variants implicated in human Müllerian duct anomalies.

BACKGROUND: Müllerian duct anomalies (MDAs) are congenital developmental disorders that present as a series of abnormalities within the reproductive tracts of females. Genetic factors are linked to MDAs and recent advancements in whole-exome sequencing (WES) provide innovative perspectives in this field. However, relevant mechanism has only been investigated in a restricted manner without clear elucidation of respective observations. METHODS: Our previous study reported that 2 of 12 patients with MDAs harbored the CHD1L variant c.348-1G>C. Subsequently, an additional 85 MDAs patients were recruited. Variants in CHD1L were screened through the in-house database of WES performed in the cohort and two cases were identified. One presented with partial septate uterus with left renal agenesis and the other with complete septate uterus, duplicated cervices and longitudinal vaginal septum. The pathogenicity of the discovered variants was further assessed by molecular dynamics simulation and various functional assays. RESULTS: Ultimately, two novel heterozygous CHD1L variants, including a missense variant c.956G>A (p.R319Q) and a nonsense variant c.1831C>T (p.R611*) were observed. The variants were absent in 100 controls. Altogether, the contribution yield of CHD1L to MDAs was calculated as 4.12% (4/97). All three variants were assessed as pathogenic through various functional analysis. The splice-site variant c.348-1G>C resulted in a 11 bp sequence skipping in exon 4 of CHD1L and led to nonsense mediated decay of its transcripts. Unlike WT CHD1L, the truncated R611* protein mislocalized to the cytoplasm, abolish the ability of CHD1L to promote cell migration and failed to interact with PARP1 owing to the loss of macro domain. The R319Q variant exhibited conformational disparities and showed abnormal protein recruitment behavior through laser microirradiation comparing with the WT CHD1L. All these variants impaired the CHD1L function in DNA damage repair, thus participating in MDAs. CONCLUSIONS: The current study not only expands the mutational spectrum of CHD1L in MDAs but determines three variants as pathogenic according to ACMG guidelines with reliable functional evidence. Additionally, the impairment in DNA damage repair is an underlying mechanism involved in MDAs.

Development of the assessment standards of the International Classification of Functioning, Disability, and Health (ICF) Geriatric Core Set through a modified Delphi method.

BACKGROUND: There is currently a lack of functional assessment tools based on the International Classification of Functioning, Disability, and Health (ICF) theoretical framework that are specific for older adults. OBJECTIVE: The aim of the present study was to develop Chinese assessment standards of the ICF Geriatric Core Set for functional evaluation of older adults. METHODS: A two-stage study process was conducted to develop the assessment standards of the ICF Geriatric Core Set: establishment of candidate assessment standards, and a modified Delphi consensus process including a pilot survey and two-round formal expert survey. Thirty participants in the field of ICF and geriatric rehabilitation were recruited. The suitability of the assessment standards in the questionnaires was rated using a Likert 5-level scoring method. The arithmetic mean, the full mark ratio and the coefficient of variation (CV) were used as screening indicators for the assessment standards, and modification was made for several standards, in line with the Delphi results and the expert panel discussion. RESULTS: Thirty-three candidate assessment standards belonging to 17 categories were generated. A total of 26 and 24 experts in the field of ICF and geriatric rehabilitation participated in the two-round survey, respectively. Five standards belonging to four categories entered into the second-round survey directly, five standards belonged to five categories entered with minor modification, and nine standards belonging to seven categories were redesigned based on the literature and discussion of the expert panel. In the second-round survey,15 assessment standards belonging to 15 categories met the screening requirements and four assessment standards belonged to the two remaining categories that needed a criterion and which the expert panel discussed for the final decision. CONCLUSIONS: Using the modified Delphi method, the assessment standards of the ICF Geriatric Core Set have been developed.Future work should focus on the reliability and validity of the the assessment standards and their application to the health management of older adults.

Sarcopenic obesity in nursing home residents: a multi-center study on diagnostic methods and their association with instrumental activities of daily living.

BACKGROUND: Sarcopenic obesity (SO) in nursing home residents is rarely studied. We aimed to evaluate and compare the prevalence and consistency of different SO diagnostic methods and to investigate which criterion demonstrated a stronger association with instrumental activities of daily living (IADL) disability. METHODS: We consecutively recruited older adults aged ≥ 60 years, residing in 15 nursing homes in Zigong City, China. Sarcopenia obesity was defined according to the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity criteria (SOESPEN), recommending skeletal muscle mass (SMM) adjusted by body weight (SMM/W) to identify low muscle mass. Further, we adapted ESPEN criteria (SOESPEN-M) by employing SMM adjusted by body mass index (SMM/BMI). RESULTS: We included 832 participants (median age 73.0 years, 296 women). The prevalence of SOESPEN and SOESPEN-M was 43.5% and 45.3%, respectively. SOESPEN showed good consistency with SOESPEN-M (Cohen's kappa = 0.759). More than one-third of participants in the normal weight group were diagnosed with SOESPEN or SOESPEN-M. Even within the underweight group, the prevalence of SOESPEN and SOESPEN-M was 8.9% and 22.2%, respectively. Participants with IADL disability had significantly lower SMM/W and SMM/BMI, but higher fat mass percentage of body weight (FM%) than participants without IADL disability. After full adjustment for potential confounders, SOESPEN-M (OR 1.68, 95% CI 1.21 to 2.32), but not SOESPEN (OR 1.28, 95% CI 0.93 to 1.75), remained significantly associated with IADL disability. CONCLUSIONS: Both SOESPEN and SOESPEN-M showed a high prevalence among nursing home residents, even among individuals with underweight or normal weight. While SOESPEN had a good consistency with SOESPEN-M, only SOESPEN-M was independently associated with IADL disability. Screening and diagnosis of SO should be conducted in nursing home residents irrespective of BMI.

Development and validation of the coffee task: a novel functional assessment for prosthetic grip selection.

BACKGROUND: Lack of standardized assessments that explicitly quantify performance during prosthetic grip selection poses difficulty determining whether efforts to improve the design of multi-grip hands and their control approaches are successful. In this study, we developed and validated a novel assessment of multi-grip prosthetic performance: The Coffee Task. METHODS: Individuals without limb loss completed the Box and Block Test and two versions of the Coffee Task - Continuous and Segmented - with a myoelectric prosthetic emulator. On different days, participants selected prosthetic grips using pattern recognition and trigger control. Outcomes of the Continuous and Segmented Coffee Task were completion time and number of errors, respectively. Two independent raters assessed outcomes of the Coffee Task using video recordings to determine inter-rater reliability. Known-group validity was assessed by comparing outcomes with the emulator to those with an intact limb. Convergent validity was assessed through the correlation of the Coffee Task outcomes and those of the Box and Blocks Test. Responsiveness to changes with practice and control approach were assessed using the standardized response mean (SRM). RESULTS: Inter-rater reliability was high for both versions of the Coffee Task (Intra-class coefficient > 0.981). Coffee Task outcomes were moderately correlated with the Box and Blocks outcomes (|r| ≥ 0.412, p ≤ 0.007). Participants completed the Coffee Task faster with their intact limb than with the emulator (p < 0.001). Both versions of the Coffee Task were responsive to changes with training (SRM ≥ 0.81) but not control approach (SRM ≤ 0.12). CONCLUSIONS: The Coffee Task is reliable, has good known-group and convergent validity, and is responsive to changes due to practice. Future work should assess whether the Coffee Task is feasible and reliable for people with upper limb loss who use multi-grip prostheses.

Evaluating Postural Transition Movement Performance in Individuals with Essential Tremor via the Instrumented Timed Up and Go.

Flexibility in performing various movements like standing, walking, and turning is crucial for navigating dynamic environments in daily life. Individuals with essential tremor often experience movement difficulties that can affect these postural transitions, limiting mobility and independence. Yet, little research has examined the performance of postural transitions in people with essential tremor. Therefore, we assessed postural transition performance using two versions of the timed up and go test: the standard version and a more complex water-carry version. We examined the total duration of the standard and water-carry timed up and go in 15 people with and 15 people without essential tremor. We also compared the time taken for each phase (sit-to-stand phase, straight-line walk phase, stand-to-sit phase) and the turning velocity between groups. Our findings revealed decreased performance across all phases of standard and water-carry timed up and go assessments. Further, both ET and non-ET groups exhibited reduced performance during the water-carry timed up and go compared to the standard timed up and go. Evaluating specific phases of the timed up and go offers valuable insights into functional movement performance in essential tremor, permitting more tailored therapeutic interventions to improve functional performance during activities of daily living.

A Statistical Approach for Functional Reach-to-Grasp Segmentation Using a Single Inertial Measurement Unit.

The aim of this contribution is to present a segmentation method for the identification of voluntary movements from inertial data acquired through a single inertial measurement unit placed on the subject's wrist. Inertial data were recorded from 25 healthy subjects while performing 75 consecutive reach-to-grasp movements. The approach herein presented, called DynAMoS, is based on an adaptive thresholding step on the angular velocity norm, followed by a statistics-based post-processing on the movement duration distribution. Post-processing aims at reducing the number of erroneous transitions in the movement segmentation. We assessed the segmentation quality of this method using a stereophotogrammetric system as the gold standard. Two popular methods already presented in the literature were compared to DynAMoS in terms of the number of movements identified, onset and offset mean absolute errors, and movement duration. Moreover, we analyzed the sub-phase durations of the drinking movement to further characterize the task. The results show that the proposed method performs significantly better than the two state-of-the-art approaches (i.e., percentage of erroneous movements = 3%; onset and offset mean absolute error < 0.08 s), suggesting that DynAMoS could make more effective home monitoring applications for assessing the motion improvements of patients following domicile rehabilitation protocols.

Transphyseal arthroscopic anterior cruciate ligament reconstruction in children under 12 years.

BACKGROUND: The incidence of anterior cruciate ligament (ACL) injuries in children is on the rise. Despite this trend, the optimal management of these injuries remains a matter of ongoing debate. In this light, our study seeks to assess the clinical, radiological, and functional outcomes of transphyseal ACL reconstruction in preadolescent patients in the medium-term. METHODS: This prospective study included preadolescent patients aged up to 12 years who underwent ACL transphyseal reconstruction between 2010 and 2020 and had a minimum follow-up of 2 years. Clinical assessments encompassed joint stability and range of motion. Furthermore, leg length discrepancy (LLD) and femorotibial alignment were evaluated both clinically and radiologically using full-length lower limb standing radiographs. Pre- and postoperative functional outcomes were assessed using the International Knee Documentation Committee (IKDC) and Lysholm scales, and the return to normal sports activity was evaluated using the ACL-Return to Sport after Injury (ACL-RSI) scale. Complications and relevant follow-up data were also recorded. Statistical analyses were conducted to evaluate these outcomes. RESULTS: A total of 35 preadolescent patients, consisting of 24 males and 11 females, with a mean age at surgery of 11.2 ± 0.7 years (8.7-12), were included in the study. The mean follow-up was 52.3 ± 20.7 months (24.1-95.9). No significant growth disturbances or clinically relevant LLD were evidenced. All patients demonstrated clinically stable knees with full range of motion at the 2-year follow-up. There were statistically significant improvements in pre- and postoperative IKDC (39.3 ± 13.5 vs. 99.7 ± 0.8, p < 0.005) and Lysholm scores (48.2 ± 15.1 vs. 99.6 ± 1.4, p < 0.005). All but two patients were able to return to their pre-injury level of sports activity, with a mean ACL-RSI score of 93.5 ± 1.3. The analysis revealed an 8.6% rerupture rate and an 11.4% rate of contralateral ACL injuries, with 5-year survival rates of 92.3% and 88.8%, respectively. Subgroup analyses based on age, gender, surgical delay, or associated meniscal lesions did not reveal any significant differences in functional outcomes. Additionally, there was no discernible relationship between age or timing of ACL reconstruction and the risk of meniscal injuries. CONCLUSIONS: Our study reinforces the value of ACL reconstruction in skeletally immature preadolescent patients, with transphyseal technique proven to be a safe, effective, and technically simpler option, even for children under the age of 12. The findings indicate excellent functional outcomes, a high rate of successful return to sporting activities, and minimal to no incidence of growth-related complications in the medium-term. LEVEL OF EVIDENCE: Level II, prospective comparative cohort study, before and after intervention.

Developmental framework for a desktop hydrogeomorphic wetland functional assessment derived from field-based data.

With loss of wetlands and their associated ecosystem services within landscapes, it is imperative to be able to understand the change in ecological functions underlying these services. Field-based functional assessments can produce a range of specific scores among a robust set of functions but are time and cost prohibitive as the number of wetlands assessed increases. Remote-based functional assessments are an alternative for broad scale assessments, but trade-off cost for limitations in scoring and functional assemblage. To address these concerns, we created a framework for the development of the Hydrogeomorphic Remote Assessment of Wetland Function (HGM-RAWF). Rooted in the hydrogeomorphic approach of an existing field-based functional assessment and its underlying models, this remote functional assessment substitutes field-based assessment methods with remotely assessed proxies. As potential remote proxies were determined through literature review and statistically screened for use in the remote assessment, a field-based reference wetland database of 222 freshwater wetlands in the Mid-Atlantic Region provided a baseline by which remote data could be compared and calibrated. The resulting HGM-RAWF protocol remotely assesses seven hydrology and biogeochemistry functions in the Mid-Atlantic with assessment scores similar to its field-based counterparts. With noted limitations, the HGM-RAWF framework provides the means to create desktop functional assessments across broad geographic scales with the diversity and specificity of field-based assessments at the reduced costs associated with remote assessments. Its basis in the HGM approach and use of public spatial datasets allows the framework to be adopted regionally and can be used as a model for national wetland functional assessment.

Exploring the Implications of Inter-Limb Asymmetries on Sprint, Agility, and Jump Performance in Young Highly-Trained Basketball Athletes: Is There a Relevant Threshold?

Background and Objectives: This study aimed to investigate the magnitude of vertical jump inter-limb asymmetries among young highly-trained basketball athletes and to analyze its impact on sport performance, specifically in sprints, agility, and vertical jumps. Materials and Methods: A unilateral countermovement jump (CMJ) was employed to determine Inter-limb Index Asymmetry (IAI) in 320 participants aged from 14 to 18 years, from the Valencia Basket youth academy. IAI was categorized into three groups: 0-9.9%, 10-14.9%, and >15%. The relationship between IAI and performance variables was analyzed through correlation studies (Pearson or Spearman's). The influence of IAI magnitude was assessed using ANOVA or Kruskal-Wallis analysis, with leg dominance as a covariable. SPSS Statistics version 26 was used for analysis. Results: Among all the participants, the mean IAI was 10.6%. Correlation studies revealed non-significant values (p < 0.05) between IAI and sport performance variables. The three IAI magnitude groups did not show statistically significant differences in sprint, agility, and jump outcomes. Leg dominance did not seem to influence performance outcomes, except for unilateral CMJ. Conclusions: The results obtained challenge the assumption that an IAI above 10% negatively affects sprint, agility, or jump performance in young basketball athletes. Notably, the magnitude of IAI did not influence sport performance parameters, suggesting that the 10-15% threshold from previous studies may not be applicable to this population. The study emphasizes the need to understand lower-limb asymmetries in the context of specific sport task performance, considering the potential evolution over time among affected young athletes.

Patients' Perceptions Regarding the Relevance of Items Contained in the Functional Assessment of Cancer Therapy Kidney Symptom Index-19.

BACKGROUND: There is a lack of consensus regarding the optimal method of assessing health-related quality of life (HR-QOL) among patients with metastatic renal cell carcinoma (mRCC). This study explored the perceived relevance of items that make up the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), as judged by patients with mRCC. METHODS: This was a multinational cross-sectional survey. Eligible patients responded to a questionnaire composed of 18 items that assessed the perceived relevance of each item in the FKSI-19 questionnaire. Open-ended questions assessed additional issues deemed relevant by patients. Responses were grouped as relevant (scores 2-5) or nonrelevant (score 1). Descriptive statistics were collated, and open-ended questions were analyzed and categorized into descriptive categories. Spearman correlation statistics were used to test the association between relevance and clinical characteristics. RESULTS: A total of 151 patients were included (gender: 78.1 M, 21.9F; median age: 64; treatment: 38.4 immunotherapy, 29.8 targeted therapy, 13.9 immuno-TKI combination therapy) in the study. The most relevant questions evaluated fatigue (77.5), lack of energy (72.2), and worry that their condition will get worse (71.5). Most patients rated blood in urine (15.2), fevers (16.6), and lack of appetite (23.2) as least relevant. Qualitative analysis of open-ended questions revealed several themes, including emotional and physical symptoms, ability to live independently, effectiveness of treatment, family, spirituality, and financial toxicity. CONCLUSION: There is a need to refine widely used HR-QOL measures that are employed among patients diagnosed with mRCC treated with contemporary therapies. Guidance was provided for the inclusion of more relevant items to patients' cancer journey.

Fatigue and health-related quality of life in paroxysmal nocturnal haemoglobinuria: A post hoc analysis of the pegcetacoplan PEGASUS trial data.

OBJECTIVES: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, non-malignant haematological disorder associated with disabling fatigue and reduced health-related quality of life. Post hoc analysis of PEGASUS phase 3 trial (NCT03500549) characterised improvements in patient-reported fatigue measured by functional assessment of chronic illness therapy-fatigue (FACIT-fatigue) instrument item-level ratings for pegcetacoplan and eculizumab for the treatment of PNH. METHODS: Item-level responder analysis was conducted on a ≥2-level change from baseline (CFB) clinically important response (CIR) for the FACIT-fatigue 13 individual items rated on a 5-level Likert scale. We evaluated ≥2-level change against the minimal clinically important difference (MCID) of the FACIT-fatigue total score (≥5 points) and clinical parameters, haemoglobin (Hb; ≥1 g/dL) and normalised absolute reticulocyte count (ARC; 30-100 pg/cells). Logistic regressions estimated baseline-to-Week-16 FACIT-fatigue item-level transitional probabilities; Kaplan-Meier analysis estimated time to FACIT-fatigue item CIR. RESULTS: Pegcetacoplan versus eculizumab was associated with significantly greater odds of Week 16 CIR across 8/13 items and on total score MCID (OR [CI] = 11.19 [3.73, 33.57]) and faster times to responses. The item-level CIR threshold also showed clinical relevance on Hb level and ARC normalization. CONCLUSIONS: Compared with eculizumab, pegcetacoplan was associated with clinically meaningful greater improvements on a majority of FACIT-fatigue items.

Intrinsic capacity: an under-researched concept in geriatrics.

In 2015, the World Health Organisation (WHO) introduced the concept of intrinsic capacity (IC) as part of a new public health model for healthy ageing. IC refers to the overall combination of an individual's physical and mental capacities, and is promoted as a new positive approach to the health and wellbeing of older adults. However, there is still insufficient evidence that implementing IC leads to better care for older adults. Moreover, the current operationalisations of IC lead to confusion and redundant research. In this commentary, we discuss whether the concept of IC has added value for geriatrics, and describe the main issues related to its conceptualisation, measurement, and application. We argue that there is a need to clarify and validate the concept of IC, including independent evidence regarding its feasibility and acceptance in clinical practice.

Reliability and validity of the simplified Chinese version of the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator.

PURPOSE: This study aimed to translate and culturally adapt the immune checkpoint modulator (ICM) subscale of the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM) scale and to validate the FACT-ICM scale in Chinese cancer patients receiving immune checkpoint inhibitors (ICIs) treatment. METHODS: In total, 354 cancer patients treated with ICIs were included in our cross-sectional study including 2 phases. Firstly, the ICM subscale was translated and culturally adapted by standardized procedures. Then the FACT-ICM scale was validated, which included item analysis, content validity, floor and ceiling effects, internal consistency reliability, test-retest reliability, construct validity, convergent/divergent validity, and known-group validity. RESULTS: The content validity indexes at the item and scale level of the ICM subscale were greater than 0.8. No floor and ceiling effects were found. The Cronbach's α and McDonald's omega coefficients of the simplified Chinese version of the FACT-ICM scale were 0.935 and 0.936, and the intraclass correlation coefficient was 0.833 (95% confidence interval: 0.574-0.940). Confirmatory factor analysis confirmed the 5-subscale structure of the simplified Chinese version of the FACT-ICM scale (χ2/df = 2.144, RMSEA = 0.057, SRMR = 0.072, and CFI = 0.848). Convergent and divergent validity further supported the construct validity of the simplified Chinese version of the FACT-ICM scale. The known-group validity of the simplified Chinese version of the FACT-ICM scale was confirmed in patients with different physical statuses. CONCLUSIONS: The simplified Chinese version of the FACT-ICM scale is a valid and reliable instrument and can be used in clinical practice and research on cancer patients receiving ICIs treatment.

Prospective Evaluation of Health-Related Quality of Life in Patients with Metastatic Urothelial Carcinoma Undergoing Immunotherapy with Pembrolizumab: Symptom Burden Can Predict Survival.

INTRODUCTION: Despite the fact that guidelines recommend monitoring of quality of life during all phases of treatment in urothelial carcinoma, prospective data about health-related quality of life (HRQoL) in metastatic urothelial carcinoma undergoing immunotherapy are sparse. Consequently, we performed a prospective clinical pilot study about HRQoL using the Functional Assessment of Cancer Therapy - Immune Checkpoint Modulator (FACT-ICM) questionnaire. MATERIALS AND METHODS: Formally, this study is a prospective uni-centric noninterventional observation from January 2021 to December 2021. RESULTS: Fourteen patients with a mean age of 73.9 years (SD 8.8) participated in the study. The physical well-being subscale of FACT-G is most impaired during therapy with mean scores of 7.5, 6.2, and 4.0 followed by the emotional well-being. The FACT-G total score is stable during therapy with mean scores of 51.1, 50.4, and 48.0 and it is not significantly decreasing during therapy (p = 0.317). Furthermore, the symptom burden of these patients is low and not significantly changing over time (p = 0.500), but survival decreases significantly if symptom burden is high (FACT-ICM score over 40; p < 0.001). CONCLUSION: Physical and emotional needs have a strong impact on HRQoL and should be dealt with during treatment. If symptom burden is high, survival decreases. This needs further evaluation.

Validation of the Short Form of Korean-Everyday Cognition (K-ECog).

BACKGROUND: Evaluating the activities of daily living (ADL) is an important factor for diagnosing dementia. The Everyday Cognition (ECog) scale was developed to measure ADL changes that were correlated with specific neuropsychological impairments. A short form of the ECog (ECog-12) was also developed, consisting of 12 items, two from each of the six cognitive domains of the ECog. The Korean full version of ECog (K-ECog) has recently been standardized, but the need for a shortened version has been raised in clinical practice. The purpose of this study was to develop a Korean version of ECog-12 (K-ECog-12) and to verify its reliability and validity by comparing those to the full version of K-ECog. METHODS: The participants were 267 cognitively normal older adults (CN), 183 patients with mild cognitive impairment (MCI), and 89 patients with dementia. The Korean-Mini Mental State Examination (K-MMSE), Korean-Montreal Cognitive Assessment (K-MoCA), and Short form of Geriatric Depression Scale (SGDS) were administered to all participants. The K-ECog and Korean-Instrumental Activities of Daily Living (K-IADL) were rated by the informants of patients. RESULTS: K-ECog-12 was newly constructed by replacing one item for the visuospatial function in the original ECog-12 with another one through an item response theory analysis on Korean data. The internal consistencies (Cronbach's α) of K-ECog-12 and K-ECog were 0.95 and 0.99, respectively. The test-retest reliabilities (Pearson's r) were 0.67 for K-ECog-12 and 0.73 for K-ECog. The K-ECog-12 was significantly correlated with K-ECog as well as K-IADL, K-MMSE, and K-MoCA. The K-ECog-12 scores differed significantly between the CN, MCI, and dementia groups, as did the K-ECog scores. Receiver operating characteristic curve analyses showed that K-ECog-12, like K-ECog, could differentiate MCI and dementia patients from CN as well. CONCLUSION: The K-ECog-12 is as reliable and valid as the K-ECog in assessing ADL. Therefore, K-ECog-12 can be used as an alternative to the K-ECog in clinical and community settings in Korea.

How can we identify subglottic stenosis in patients with suspected obstructive disease?

PURPOSE: Subglottic stenosis, a rare condition of the upper airway, is frequently misdiagnosed as obstructive lung disease. The aim of this study was to investigate whether subglottic stenosis could be identified and distinguished from asthma and chronic obstructive pulmonary disease (COPD) using spirometry or the dyspnea index (DI). METHODS: The study population included 43 patients with asthma, 31 patients with COPD and 50 patients with subglottic stenosis planned to undergo endoscopic intervention. All patients completed the DI and underwent dynamic spirometry registering both inspiratory and expiratory volumes and flows, including the expiratory disproportion index (EDI), the ratio of forced expiratory volume in 1 s to peak expiratory flow. One-way analysis of variance assessed the discrepancy of the variables among the study groups, and receiver operating curve (ROC) analysis determined the measurement with the best discriminatory power providing a cutoff value, maximizing both sensitivity and specificity. RESULTS: The only statistically significant variables differing between all three groups were the EDI and the DI. The EDI showed an excellent area under the ROC curve (0.99, p < 0.001) with a cutoff value of 0.39 (98% sensitivity, 96% specificity), followed by DI (0.87, p < 0.001) with a cutoff score of > 25 (83% sensitivity and 78% specificity). CONCLUSION: In patients with dyspnea of unknown cause, an increase in EDI should arouse a suspicion of extrathoracic airway obstruction, advocating for further evaluation with laryngotracheoscopy.

Assessment of an IMU-Based Experimental Set-Up for Upper Limb Motion in Obese Subjects.

In recent years, wearable systems based on inertial sensors opened new perspectives for functional motor assessment with respect to the gold standard motion capture systems. The aim of this study was to validate an experimental set-up based on 17 body-worn inertial sensors (Awinda, Xsens, The Netherlands), addressing specific body segments with respect to the state-of-the art system (VICON, Oxford Metrics Ltd., Oxford, UK) to assess upper limb kinematics in obese, with respect to healthy subjects. Twenty-three obese and thirty healthy weight individuals were simultaneously acquainted with the two systems across a set of three tasks for upper limbs (i.e., frontal arm rise, lateral arm rise, and reaching). Root Mean Square error (RMSE) was computed to quantify the differences between the measurements provided by the systems in terms of range of motion (ROM), whilst their agreement was assessed via Pearson's correlation coefficient (PCC) and Bland-Altman (BA) plots. In addition, the signal waveforms were compared via one-dimensional statistical parametrical mapping (SPM) based on a paired t-test and a two-way ANOVA was applied on ROMs. The overall results partially confirmed the correlation and the agreement between the two systems, reporting only a moderate correlation for shoulder principal rotation angle in each task (r~0.40) and for elbow/flexion extension in obese subjects (r = 0.66), whilst no correlation was found for most non-principal rotation angles (r < 0.40). Across the performed tasks, an average RMSE of 34° and 26° was reported in obese and healthy controls, respectively. At the current state, the presence of bias limits the applicability of the inertial-based system in clinics; further research is intended in this context.