Summary Scores Research Articles

Efficacy of Real-Time Feedback Exercise Therapy in Patients Following Total Hip Arthroplasty: Protocol for a Pilot Cluster-Randomized Controlled Trial.

Osteoarthritis of the hip joint is an increasing functional and health-related problem. The most common surgical treatment is hip replacement to reduce pain and improve function. Rehabilitation after total hip arthroplasty (THA) is not regulated in Austria and mostly depends on the patient's own initiative and possibilities. Functional deficits, such as valgus thrust of the leg, functional Trendelenburg gait, or Duchenne limp, are characteristic symptoms before and, due to the performance learning effect prior to surgery, also after the operation. Addressing these deficits is possible through neuromuscular-focused exercise therapy. The efficacy of such therapy relies significantly on the quality of performance, the frequency of exercise, and the duration of engagement. Enhancing sustainability is achievable through increased motivation and real-time feedback (RTF) on exercise execution facilitated by digital feedback systems. This study will be performed to quantify the medium-term effectiveness of digital home exercise feedback systems on functional performance following THA. A clinical trial with a cluster-randomized, 2-arm, parallel-group design with an 8-week intervention phase and subsequent follow-ups at 3 and 6 months postsurgery will be conducted. Feedback during exercising will be provided through a blended-care program, combining a supervised group exercise program with a self-developed digital feedback system for home exercise. In total, 70 patients will be recruited for baseline. The primary outcome parameters will be the frontal knee range of motion, pelvic obliquity, and lateral trunk lean. Secondary outcomes will be the sum scores of patient-reported outcomes and relevant kinematic, kinetic, and spatiotemporal parameters. The trial started in January 2024, and the first results are anticipated to be published by June 2025. RTF-supported home exercise is expected to improve exercise execution quality and therapeutic adherence compared to using paper instructions for excise guidance. The anticipated findings of this study aim to offer new insights into the effect of a blended-care program incorporating digital RTF on exercise therapy after unilateral THA, in addition to knowledge on the functional status 3 and 6 months postsurgery, for further improvement in the development of rehabilitation guidelines following THA. ClinicalTrials.gov: NCT06161194; https://clinicaltrials.gov/study/NCT06161194. PRR1-10.2196/59755.

Continuity and coordination of care for childhood cancer survivors with multiple chronic conditions: Results from the Childhood Cancer Survivor Study.

Continuity and coordination-of-care for childhood cancer survivors with multiple chronic conditions are understudied but critical for appropriate follow-up care. From April through June 2022, 800 Childhood Cancer Survivor Study participants with two or more chronic conditions (one or more severe/life-threatening/disabling) were emailed the "Patient Perceived Continuity-of-Care from Multiple Clinicians" survey. The survey asked about survivors' main (takes care of most health care) and coordinating (ensures follow-up) provider, produced three care-coordination summary scores (main provider, across multiple providers, patient-provider partnership), and included six discontinuity indicators (e.g., having to organize own care). Discontinuity (yes/no) was defined as poor care on one or more discontinuity item. Chi-square tests assessed associations between discontinuity and sociodemographics. Modified Poisson regression models estimated prevalence ratios (PRs) for discontinuity risk associated with the specialty and number of years seeing the main and coordinating provider, and PRs associated with better scores on the three care-coordination summary measures. Inverse probability weights adjusted for survey non-participation. A total of 377 (47%) survivors responded (mean age 48 years, 68% female, 89% non-Hispanic White, 78% privately insured, 74% ≥college graduate); 147/373 (39%) reported discontinuity. Younger survivors were more likely to report discontinuity (chi-square p=.02). Seeing the main provider ≤3 years was associated with more prevalent discontinuity (PR; 95%CI) (1.17; 1.02-1.34 vs≥10 years). Cancer specialist main providers were associated with less prevalent discontinuity (0.81; 0.66-0.99 vs. primary care). Better scores on all three care-coordination summary measures were associated with less prevalent discontinuity: main provider (0.73; 0.64-0.83), across multiple providers (0.81; 0.78-0.83), patient-provider partnership (0.85; 0.80-0.89). Care discontinuity among childhood cancer survivors is prevalent and requires intervention.

Comprehensive four-year disease progression assessment of myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is a heterogeneous neuromuscular disorder characterized by progressive muscle weakness and myotonia. This study investigates the progression of muscular strength and function over a four-year period. Patients with DM1 were examined at baseline and four years later. The following metrics were assessed over time: muscle strength (Medical Research Council-sumscore), hand-grip strength (Martin-Vigorimeter), hand-grip relaxation time (myotonia), and limitations in activities of daily living and (DM1ActivC questionnaire). A total of 648 patients entered the registry. Recruitment and follow-up is ongoing. In our manuscript, we focus on, 187 patients who were followed for 4 years. A significant decline in MRC sum score was observed, with distal muscles showing more deterioration. Hand-grip strength decreased significantly, with notable differences between sex and phenotype classified by disease onset. Surprisingly, an improvement of myotonia was observed. Follow-up analysis revealed a significant interaction between myotonia and grip-strength over time. Thus, the improvement in myotonia is likely explained by decreased in grip strength. Finally, there was a significant reduction in DM1ActivC score, indicating decreased activity and social participation. This study demonstrated variability in disease progression depending on sex, phenotype and disease status. This research demonstrates a nuanced pattern of disease progression, highlighting the need to combine different outcome measures to fully understand the complexity of DM1.

A Multicenter Phase II Trial of Ruxolitinib for Treatment of Corticosteroid Refractory Sclerotic Chronic Graft-Versus-Host Disease.

Sclerotic chronic graft-versus-host disease (cGVHD) represents a highly morbid and refractory form of cGVHD, and novel therapies for sclerotic cGVHD are critically needed. This study aimed to determine the efficacy of ruxolitinib in patients with corticosteroid refractory sclerotic cGVHD. In a single-arm multicenter phase II trial (N = 47), adults with sclerotic cGVHD refractory to corticosteroids and ≥one additional line of systemic therapy for cGVHD received ruxolitinib for ≥six months (ClinicalTrials.gov identifier: NCT03616184). The primary end point was complete or partial response (PR) in skin and/or joint defined according to the 2014 National Institute of Health cGVHD Consensus Criteria. Following the use of ruxolitinib for a median of 11 months, PR in skin and/or joints was noted in 49% (95% CI, 34 to 64) at 6 months, with 45% having joint and fascia response and 19% having skin response. The duration of skin/joint response was 77% (95% CI, 48 to 91) at 12 months. Overall cGVHD PR was noted in 47% (95% CI, 32 to 61). Improvement in Lee Symptom Scale summary and skin subscale scores was noted in 38% of patients. With a cumulative incidence of treatment failure of 20.8% (95% CI, 10.0 to 34.1), nonrelapse mortality (NRM) of 2.2% (95% CI, 0.17 to 10.3), and no recurrent malignancy, failure-free survival (FFS) was 77.1% (95% CI, 61.3 to 87.0) at 12 months. Ruxolitinib was overall well tolerated with no new safety signals. The use of ruxolitinib was associated with relatively high rates of skin/joint responses and overall cGVHD responses, improvement in patient-reported outcomes, low NRM, and high FFS in patients with refractory sclerotic cGVHD. Ruxolitinib offers an effective treatment option for refractory sclerotic cGVHD.

Surviving Critical Care: A Follow-Up Study Assessing Pulmonary Function, Cardiopulmonary Exercise Testing, and Quality of Life in COVID-19-Affected Patients

Introduction: Survivors of severe COVID-19 face complex challenges and a high degree of pulmonary sequelae. Therefore, we aim to describe their ongoing health burden. Methods: In this single-center prospective cohort study, COVID-19 ICU survivors were invited 3 and 6 months after ICU discharge. We examined pulmonary function with pulmonary function tests (PFT) and cardiopulmonary exercise testing (CPET), and we established health-related quality of life (HRQL) and health status (HS) with the EuroQol five-dimension five-level (EQ-5D-5L), the short-form health survey 12 (SF-12), and the modified British Medical Research Council dyspnea scale (mMRC) questionnaires. Results: Out of the 53 individuals screened, 23 participated in this study. Throughout both assessment points, participants maintained PFT results within range, apart from a decline in the transfer factor of the lung for carbon monoxide (TLCO). CPET showed improved fitness but persistent ventilatory deficiencies, indicated by altered dead space ventilation (VD/VT) and elevated arterial-alveoli gradient for oxygen (AaDO2). HRQL and HS remained compromised, with both physical (PCS) and mental component summary (MCS) scores significantly lower than the standardized norm population scores. Also, there was a rise in the prevalence of issues related to mobility, pain/discomfort, and anxiety/depression, and an increase in reported dyspnea. Conclusion: These results enhance our comprehension of the complex difficulties faced by COVID-19 ICU survivors. Six months post-discharge, CPET revealed the presence of ventilatory insufficiencies. Additionally, there was a decline in HRQL and HS, notably affected by mental health concerns and an increase in the level of dyspnea.

Validity of the Musculoskeletal Tumor Society Score for lower extremity in patients with bone sarcoma or giant cell tumour of bone undergoing bone resection and reconstruction surgery in hip and knee

BackgroundThe Musculoskeletal Tumor Society Score (MSTS) is widely used to evaluate functioning following surgery for bone and soft-tissue sarcoma. However, concerns have been raised about its content validity due to the lack of patient involvement during item development. Additionally, literature reports inconsistent results regarding data quality and structural validity. This study aimed to evaluate content, structural and construct validity of the Danish version of the MSTS for lower extremity (MSTS-LE).MethodsThe study included patients from three complete cohorts (n = 87) with bone sarcoma or giant cell tumour of bone who underwent bone resection and reconstruction surgery in hip and knee. Content validity was evaluated by linking MSTS items to frameworks of functioning, core outcome sets and semi-structured interviews. Data quality, internal consistency and factor analysis were used to assess the underlying structure of the MSTS. Construct validity was based on predefined hypotheses of correlation between the MSTS and concurrent measurements.ResultsContent validity analysis revealed concerns regarding the MSTS. The MSTS did not sufficiently cover patient-important functions, the item Emotional acceptance could not be linked to the framework of functioning, the items Pain and Emotional acceptance pertained to domains beyond functioning and items’ response options did not match items. A two-factor solution emerged, with the items Pain and Emotional acceptance loading highly on a second factor distinct from functioning. Internal consistency and construct validity showed values below accepted levels.ConclusionThe Danish MSTS-LE demonstrated inadequate content validity, internal consistency, and construct validity. In addition, our analyses did not support unidimensionality of the MSTS. Consequently, the MSTS-LE is not a simple reflection of the construct of functioning and the interpretation of a sum score is problematic. Clinicians and researcher should exercise caution when relying solely on MSTS scores for assessing lower extremity function. Alternative outcome measurements of functioning should be considered for the evaluation of postoperative function in this patient group.

Converting PROMIS®-29 v2.0 profile data to SF-36 physical and mental component summary scores in patients with cardiovascular disorders

BackgroundHealth-related quality of life (HRQL) has become an important outcome parameter in cardiology. The MOS 36-ltem Short-Form Health Survey (SF-36) and the PROMIS-29 are two widely used generic measures providing composite HRQL scores. The domains of the SF-36, a well-established instrument utilized for several decades, can be aggregated to physical (PCS) and mental (MCS) component summary scores. Alternative scoring algorithms for correlated component scores (PCSc and MCSc) have also been suggested. The PROMIS-29 is a newer but increasingly used HRQL measure. Analogous to the SF-36, physical and mental health summary scores can be derived from PROMIS-29 domain scores, based on a correlated factor solution. So far, scores from the PROMIS-29 are not directly comparable to SF-36 results, complicating the aggregation of research findings. Thus, our aim was to provide algorithms to convert PROMIS-29 data to well-established SF-36 component summary scores.MethodsData from n = 662 participants of the Berlin Long-term Observation of Vascular Events (BeLOVE) study were used to estimate linear regression models with either PROMIS-29 domain scores or aggregated PROMIS-29 physical/mental health summary scores as predictors and SF-36 physical/mental component summary scores as outcomes. Data from a subsequent assessment point (n = 259) were used to evaluate the agreement between empirical and predicted SF-36 scores.ResultsPROMIS-29 domain scores as well as PROMIS-29 health summary scores showed high predictive value for PCS, PCSc, and MCSc (R2 ≥ 70%), and moderate predictive value for MCS (R2 = 57% and R2 = 40%, respectively). After applying the regression coefficients to new data, empirical and predicted SF-36 component summary scores were highly correlated (r > 0.8) for most models. Mean differences between empirical and predicted scores were negligible (|SMD|<0.1).ConclusionsThis study provides easy-to-apply algorithms to convert PROMIS-29 data to well-established SF-36 physical and mental component summary scores in a cardiovascular population. Applied to new data, the agreement between empirical and predicted SF-36 scores was high. However, for SF-36 mental component summary scores, considerably better predictions were found under the correlated (MCSc) than under the original factor model (MCS). Additionally, as a pertinent byproduct, our study confirmed construct validity of the relatively new PROMIS-29 health summary scores in cardiology patients.

Using eZIS to Predict Progression from MCI to Dementia in Three Years.

(1) Background: Mild cognitive impairment (MCI) due to Alzheimer's disease (AD) progresses to dementia at a higher annual rate, while other MCIs may remain stable or even improve over time. Discriminating progressive from non-progressive cases of MCI is crucial and challenging. (2) Methods: A retrospective study of individuals with MCI was conducted at a university hospital located in southern Taiwan. The researchers collected demographic data, comorbidities, the scores of cognitive tests, three easy Z-score imaging system (eZIS) indicators (severity, extent, and ratio), Fazekas scale scores, mesial temporal atrophy (MTA) scores, clinical outcomes including deterioration of Cognitive Abilities Screening Instrument, Mini-mental State Examination, Clinical Dementia Rating Sum of Box scores, and the conversion from MCI to dementia. Those who converted to dementia in three years and non-converters were compared by the three eZIS indicators to test the predictive utility, and the clinical outcomes were evaluated by regression and ROC curve analysis. (3) Results: The three eZIS indicators were significantly higher in the group of progressive MCI than in stable MCI. eZIS severity is positively correlated with a deterioration in the scores of the Cognitive Abilities Screening Instrument and Clinical Dementia Rating Sum of Box. eZIS severity is also positively correlated with conversion from MCI to dementia. The AUC for severity is 0.719, and the optimal cutoff value of severity for predicting conversion is 1.22. (4) Conclusions: During three years of follow-up, MCI individuals with greater eZIS severity were significantly associated with worse cognitive assessment scores and a higher conversion rate to dementia.

Characterization and natural history of patients with LMNA-related dilated cardiomyopathy in the phase 3 REALM-DCM trial.

LMNA-related dilated cardiomyopathy (DCM) is a rare disease with an incompletely defined phenotype. The phase 3 REALM-DCM trial evaluated a potential disease-modifying therapy for LMNA-related DCM but was terminated due to futility without safety concern. This study utilized pooled data from REALM-DCM to descriptively characterize the phenotype and progression of LMNA-related DCM in a contemporary cohort of patients using common heart failure (HF) measures. REALM-DCM enrolled patients with stable LMNA-related DCM, an implanted cardioverter defibrillator or cardiac resynchronization therapy defibrillator, and New York Heart Association (NYHA) Class II/III HF symptoms. Between 2018 and 2022, 77 patients took part in REALM-DCM. The median patient age was 53years (range: 23-72), and 57% were male. Overall, 88% of patients had a pathogenic or likely pathogenic LMNA variant, and 12% had a variant of uncertain significance with a concordant phenotype. Among patients with confirmed sequencing, 55% had a missense variant. Atrial fibrillation was present in 60% of patients; 79% of all patients had NYHA Class II and 21% had NYHA Class III HF symptoms at baseline. Median (range) left ventricular ejection fraction (LVEF), 6min walk test (6MWT) distance, Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration at baseline were 42% (23-62), 403m (173-481), 67 (18-97) and 866pg/mL (57-5248), respectively. LVEF, 6MWT distance and KCCQ-OS score were numerically lower in patients who had NYHA Class III versus II symptoms at baseline (LVEF: 38% vs. 43%; 6MWT distance: 326 vs. 413m; and KCCQ-OS score: 43 vs. 70), whereas NT-proBNP concentration was higher (1216 vs. 799pg/mL). Median follow-up was 73weeks (range: 0.4-218; 73 in NYHA Class II and 75 in NYHA Class III). Patients displayed variable change from baseline in 6MWT, KCCQ-OS and NT-proBNP values during follow-up. Overall, 25% of patients experienced ventricular tachycardia, and 8% had ventricular fibrillation. Ten (13%) patients met the composite endpoint of worsening HF (adjudicated HF-related hospitalization or urgent care visit) or all-cause death; six had NYHA Class II and four had NYHA Class III at baseline. All-cause mortality occurred in 6 (8%) patients; three had NYHA Class II and three had NYHA Class III symptoms at baseline. Findings confirm the significant morbidity and mortality associated with LMNA-related DCM despite the standard of care management. Typical measures of HF, including 6MWT distance, KCCQ-OS score and NT-proBNP concentration, were variable but correlated with NYHA class. An unmet treatment need remains among patients with LMNA-related DCM. NCT03439514.

Measuring the effect of the anti-nerve growth factor antibodies bedinvetmab and frunevetmab on quality of life in dogs and cats with osteoarthritis using a validated health-related quality of life outcome measure: an observational real-world study.

Osteoarthritis causes chronic pain, impaired joint function, decreased mobility and negatively impacts quality of life (QOL). Anti-nerve growth factor antibodies bedinvetmab for dogs and frunevetmab for cats are licensed for the alleviation of osteoarthritis pain but their QOL impact is unreported. Our aim was to determine if these therapeutics improve QOL using a validated health-related QOL measure that generates scores in four domains of QOL-energetic and enthusiastic (E/E), happy and content (H/C), active and comfortable (A/C) and calm and relaxed (C/R)-in the dog and three in the cat-vitality, comfort and emotional wellbeing (EWB). Summary scores for physical wellbeing (PWB) and emotional wellbeing (EWB) for dogs and PWB for cats are calculated from the domain scores. Animals received bedinvetmab (dogs) at 0.5-1 mg/kg or frunevetmab (cats) at 1-2.8 mg/kg by subcutaneous injection on days 0, 28 and 56 and owners completed QOL assessments within 48 hours of day 0 and on days 14, 28, 56, 63 and 70 using a study-specific app. Assessments were completed by 75 dog and 56 cat owners. By day 14 there was a statistically significant improvement (p ≤ 0.001) in PWB, EWB and all domains except C/R (p = 0.005) in dogs and in all domains and PWB in the cat. Subsequently there was a continued improvement in all domains and summary scores (p ≤ 0.001) except for H/C in the dog and EWB in the cat, which were excluded from the statistical model. The overall improvement in all domain scores in the cat and E/E and A/C in the dog exceeded the previously reported minimum important difference scores for the QOL measure, indicating a clinically significant change. Treatment with bedinvetmab and frunevetmab produced a significant improvement in the QOL of dogs and cats. This latest evidence for the use of these OA pain medications could be helpful in the clinical management of osteoarthritis and post-marketing clinical trials.

Validation of the EQ-5D-Y-5L parent-proxy version among children with juvenile idiopathic arthritis

ObjectivesJuvenile idiopathic arthritis (JIA) is the most common type of arthritis among children. It can cause joint pain and permanent physical damage, which affects mobility and daily activities. The EQ-5D-Y-3L self-report version has been validated in JIA, but the validity of EQ-5D-Y-5L remains unknown. We examined the psychometric properties of the EQ-5D-Y-5L parent-proxy version among children with JIA.MethodsWe used data from the Understanding Childhood Arthritis Network Canadian-Dutch collaboration study cohort, including patients with new-onset JIA, and those starting or stopping biologics. Clinical data and the parent-proxy version of the childhood health assessment questionnaire (CHAQ) and EQ-5D-Y-5L were collected. We evaluated the ceiling and floor effect; convergent and divergent validity using Spearman’s rank correlation; known-group validity using one-way ANOVA (Analysis of Variance) and effect size; and informativity using Shannon’s evenness index.Results467 patient visits representing 407 patients were analyzed. The EQ-5D-Y-5L had no ceiling/floor effect. The EQ-5D-Y-5L showed good convergent (e.g., EQ-5D-Y-5L pain/discomfort dimension vs. CHAQ pain index (Spearman’s r = 0.74, 95% confidence interval (C.I.): 0.69–0.79)), divergent (e.g., EQ-5D-Y-5L pain/discomfort dimension vs. CHAQ eating dimension (Spearman’s r = 0.19, 95% C.I.: 0.09–0.29)) and known-group validity (e.g., mean EQ-5D-Y-5L level summary score for patients with inactive versus active disease status, 6.34 vs. 10.52 (p < 0.001, effect size = 1.20 (95% C.I.: 0.95–1.45)). Shannon’s evenness index ranged from 0.52 to 0.88, suggesting most dimensions had relatively even distributions.ConclusionsIn this patient sample, EQ-5D-Y-5L parent-proxy version exhibited construct validity and informativity, suggesting the EQ-5D-Y-5L can be used to measure the quality of life of children with JIA.

Reduced awareness of cognitive deficits in idiopathic normal pressure hydrocephalus and its change following lumbar puncture

ObjectiveAwareness of cognitive deficits is related to executive functions and may, therefore, be sensitive to the effects of lumbar puncture (LP) in idiopathic normal pressure hydrocephalus (iNPH). Although a reduction in awareness of cognitive deficits (RACD) has been previously described in iNPH, there is a lack of systematic, psychometrically validated reports. In this study, we investigated RACD and its LP-related changes in iNPH patients and compared them with those in clinical and healthy control groups. MethodsRACD was assessed before and after lumbar puncture (LP) in 24 patients (14 iNPH, 10 other age-associated cognitive syndromes; AACS) and compared with 23 healthy controls (HC), employing two RACD measures alongside cognitive examination. Local metacognition was measured using a visual percentile-based rating system and operationalized as the t-scaled distance between the participants' task-specific performance estimations and their objective test performance (ΔTSPE). Global metacognition, targeting broader estimates of cognitive functioning (ECF), was quantified by subtracting self- from informant-obtained sum scores on a questionnaire evaluating participants' dysexecutive problems (DEX-DS). Within-group and between-group differences in ΔTSPE and DEX-DS scores were compared non-parametrically, focusing on post-LP changes. ResultsAveraged ΔTSPE was higher in the patient groups and mirrored the groups' lower objective test performance, while averaged DEX-DS showed no group difference. Following LP, group comparisons revealed iNPH-specific decrease in both RACD measures. ConclusionOur study revealed LP-related RACD changes in iNPH patients compared to those in AACS and HC participants. The results suggest a mitigation of impaired metacognitive abilities in iNPH, possibly resulting from LP-induced improvements in (local) metacognitive performance, facilitating ECF adjustment alongside a metacognitively stimulating testing procedure.

The impact of quality of life on the survival of elderly patients with end-stage renal disease: a prospective multicenter cohort study in Korea.

Quality of life (QOL) is associated with mortality in dialysis patients. However, the impact of QOL index or score on elderly patients undergoing maintenance dialysis is unclear. We analyzed the relationship between QOL domains and survival in elderly end-stage renal disease (ESRD) patients on dialysis. We included 492 incident ESRD patients aged ≥65years from a Korean nationwide prospective cohort study who were assessed for QOL with a follow-up duration of 67.3±34.6months after dialysis initiation. Their QOL was evaluated using the Kidney Disease Quality of Life (KDQOL) instrument, and the effect of each QOL domain on mortality was analyzed. Multivariable Cox regression analysis was performed to identify independent risk factors for death after adjusting for confounding factors. Low physical component summary (PCS) and Short Form-36 score were significantly associated with low survival rate (P<.001 and P=.017, respectively), whereas the mental component summary and ESRD-targeted item scores were not correlated with survival rate. Multivariable Cox regression analysis confirmed that only a high PCS score was associated with better survival (hazard ratio 0.71; 95% confidence interval 0.52-0.97; P=.031). Linear regression analysis revealed that age, sex, modified Charlson comorbidity index, albumin and intact parathyroid hormone were associated with PCS. Among the PCS items, only the physical functioning score was significantly associated with mortality (P=.017). PCS was an independent risk factor for death in elderly ESRD patients. A higher physical functioning score was associated with a better outcome, suggesting the importance of physical condition in elderly dialysis patients.

Initial interpretation scores of screening mammograms and cancer detection in BreastScreen Norway

PurposeTo explore the association between radiologists’ interpretation scores, early performance measures and cumulative reading volume in mammographic screening. MethodWe analyzed 1,689,731 screening examinations (3,379,462 breasts) from BreastScreen Norway 2012–2020, all breasts scored 1–5 by two independent radiologists. Score 1 was considered negative/benign and score ≥2 positive in this scoring system. We performed descriptive analyses of recall, screen-detected cancer, positive predictive value (PPV) 1, mammographic features and histopathological characteristics by breast-based interpretation scores, and cumulative reading volume by examination-based interpretation scores. ResultsCounting breasts and not women, 3.9 % (132,570/3,379,462) had a score of ≥2 by one or both radiologists. Of these, 84.8 % (112,440/132,570) were given a maximum score 2. Total recall rate was 1.6 % (53,735/3,379,462), 69.3 % (37,220/53,735) given maximum score 2. Among the 0.3 % (9733/3,379,462) diagnosed with screen-detected cancer, 34.6 % (3369/9733) had maximum score 3. The percentages of recall, screen-detected cancer and PPV-1 increased by increasing the sum of scores assigned by two radiologists (p < 0.001 for trend). Higher proportions of masses were observed among recalls and screen-detected cancers with low scores, and higher proportions of spiculated masses were observed for high scores (p < 0.001). Proportions of invasive carcinoma, histological grade 3 and lymph node positive tumors were higher for high versus low scores (p < 0.001). The proportion of examinations scored 1 increased by cumulative reading volume. ConclusionsWe observed higher rates of recall and screen-detected cancer and less favorable histopathological tumor characteristics for high versus low interpretation scores. However, a considerable number of recalls and screen-detected cancers had low interpretation scores.

Tissue Doppler ultrasound of arm muscles to assess myotonia in myotonic dystrophies: An exploratory study.

Myotonia is a key symptom of myotonic dystrophies (DM), and its quantification is challenging. This exploratory study evaluated the utility of tissue Doppler ultrasound (TDU) to assess myotonia in DM. Twelve DM patients (seven type-1 DM [DM1] and five type-2 DM [DM2]) and 20 age-matched healthy subjects were included in this cross-sectional study. After measuring cross-sectional areas of the flexor digitorum superficialis (FDS) and extensor digitorum communis (EDC) muscles in a resting state, muscle contraction/relaxation time, time to peak tissue velocity, peak tissue velocity and velocity gradients of these muscles were measured via TDU while performing forced fist unclenching after fist closure. Additionally, grip strength, Medical Research Council Sum score and patient-reported myotonia severity scores were assessed. DM1 and DM2 patients had a lower grip strength than healthy subjects (p = .0001/p = .002). Patient-reported myotonia did not differ between DM1 and DM2 patients. DM1 patients revealed FDS and EDC atrophy compared to DM2 patients and healthy subjects (p = .003/p = .004). TDU revealed prolonged muscle contraction and relaxation times in both DM subtypes, with prolonged time to reach FDS peak relaxation velocity and altered peak FDS relaxation velocity only in DM1 patients (p = .03/p = .003). Peak FDS relaxation velocity correlated inversely with C(C)TG repeat numbers in DM patients. Sensitivity of TDU parameters to detect myotonic dystrophy varied between 50% and 75%, with a specificity of 95%. Our exploratory study suggests that TDU could serve as a novel tool to quantify myotonia in DM patients, but larger follow-up studies are warranted to validate its diagnostic accuracy.

A person-reported cumulative social risk measure does not show bias by income and education

BackgroundSocial risk such as housing instability, trouble affording medical care and food insecurity are a downstream effect of social determinants of health (SDOHs) and are frequently associated with worse health. SDOHs include experiences of racism, sexism and other discrimination as well as differences in income and education. The collective effects of each social risk a person reports are called cumulative social risk. Cumulative social risk has traditionally been measured through counts or sum scores that treat each social risk as equivalent. We have proposed to use item response theory (IRT) as an alternative measure of person-reported cumulative social risk as IRT accounts for the severity in each risk and allows for more efficient screening with computerized adaptive testing.MethodsWe conducted a differential item functioning (DIF) analysis comparing IRT-based person-reported cumulative social risk scores by income and education in a population-based sample (n = 2122). Six social risk items were analyzed using the two-parameter logistic model and graded response model.ResultsAnalyses showed no DIF on an IRT-based cumulative social risk score by education level for the six items examined. Statistically significant DIF was found on three items by income level but the ultimate effect on the scores was negligible.ConclusionsResults suggest an IRT-based cumulative social risk score is not biased by education and income level and can be used for comparisons between groups. An IRT-based cumulative social risk score will be useful for combining datasets to examine policy factors affecting social risk and for more efficient screening of patients for social risk using computerized adaptive testing.

Transitioning between the EQ-5D youth and adult descriptive systems in a group of adolescents

PurposeTo investigate whether the same health state results in the same distribution of responses on the EQ-5D youth and adult descriptive systems.MethodsAdolescents aged 13–18 years with a range of health conditions and from the general school going population were recruited in South Africa (ZA) and Ethiopia (ET). In ZA participants completed the English EQ-5D-3L, EQ-5D-Y-3L and EQ-5D-5L in parallel. Whereas in ET participants completed the Amharic EQ-5D-5L and EQ-5D-Y-5L in parallel. Analysis aimed to describe the transition between youth and adult instruments and not differences between countries.ResultsData from 592 adolescents completing the EQ-5D-3L, EQ-5D-Y-3L and EQ-5D-5L (ZA) and 693 completing the EQ-5D-5L and EQ-5D-Y-5L (ET) were analysed. Adolescents reported more problems on the youth versions compared to the adult version for the dimension of mental health. 13% and 4% of adolescents who reported no problems on the EQ-5D-3L and EQ-5D-5L reported some problems on the EQ-5D-Y-3L respectively. This was less notable with transition between the five level versions with 4% of adolescents reporting more problems on the EQ-5D-Y-5L than the EQ-5D-5L. Very few adolescents reported severe problems (level 3 on the EQ-5D-3L or EQ-5D-Y-3L and level 4 and level 5 on the EQ-5D-5L or EQ-5D-5L) thus there was little variation between responses between the versions. In ZA, discriminatory power, measured on the Shannon’s Index, was higher for Y-3L compared to 3L for pain/discomfort (ΔH′=0.11) and anxiety/depression (ΔH′=0.04) and across all dimensions for Y-3L compared to 5L. Similarly, in ET discriminatory power was higher for Y-5L than 5L (ΔH′ range 0.05–0.09). Gwet’s AC showed good to very good agreement across all paired (ZA) 3L and (ET) 5L dimensions. The summary score of all EQ-5D versions were able to differentiate between known disease groups.ConclusionDespite the overall high levels of agreement between EQ-5D instruments for youth and for adults, they do not provide identical results in terms of health state, from the same respondent. The differences were most notable for anxiety/depression. These differences in the way individuals respond to the various descriptive systems need to be taken into consideration for descriptive analysis, when transitioning between instruments, and when comparing preference-weighted scores.

Parent-Clinician Communication and Prolonged Grief in Parents Whose Child Died From Cancer

ContextParent-clinician communication is essential for high-quality end-of-life (EOL) care in children with cancer. However, it is unknown how parent-clinician communication affects parents’ experience in the first two years after their child's death. ObjectivesTo examine the association between communication and prolonged grief among parents whose child died from cancer and to explore the mediation effect of preparation for EOL care. MethodsWe analyzed data from a cross-sectional survey of parents of children who died from cancer in the prior 6-24 months. We used multiple linear regression to examine the association between communication variables and prolonged grief symptoms. We also examined how preparation for EOL mediates these associations. ResultsAcross N = 124 parents, the mean age was 46 years, 82% were White, and 64% were mothers. The average PG-13 sum score was 32.7 ± 10.6 (range 11-55, with higher scores indicating greater symptom severity). Most parents reported “very good/excellent” communication with clinicians (80%), adequate prognostic information (64%), and high levels of trust (90%). Nearly 39% of parents reported feeling “not at all prepared” for their child's EOL. Compared to parents who wanted more prognostic information, parents who perceived prognostic information to be adequate had significantly lower PG-13 sum scores (36.4 ± 10.8 vs. 30.5 ± 10.1, F = 9.26, P = 0.003). Preparation for EOL fully mediated this association. ConclusionEarly bereaved parents report severe prolonged grief symptoms. Interventions focused on providing adequate prognostic information and improving preparation for EOL may mitigate parental prolonged grief symptoms in the first two years of their bereavement.

Measuring perceived utility of genomic sequencing: Development and validation of the GENEtic Utility (GENE-U) scale for adult screening

PurposeAs population-based screening programs to identify genetic conditions in adults using genomic sequencing (GS) are increasingly available, validated patient-centered outcome measures are needed to understand participants’ experience. We aimed to develop and validate an instrument to assess the perceived utility of GS in the context of adult screening. MethodsInformed by a 5-domain conceptual model, we used a 5-step approach to instrument development and validation: (1) item writing, (2) cognitive testing, (3) pilot testing and item reduction, (4) psychometric testing, and (5) evaluation of construct validity. Adults undergoing risk-based or population-based GS who had received GS results as part of ongoing research studies participated in structured cognitive interviews and 2 rounds of surveys. After item pool refinement, we conducted an exploratory factor analysis and calculated Pearson correlations with related instruments. ResultsWe derived the 18-item Adult Screening version of the GENEtic Utility scale (total sum score α = .87). Mirroring the Pediatric Diagnostic version, the instrument has a 2-factor structure, including an Informational Utility subscale (14 items, α = .89) and an Emotional Utility subscale (4 items, α = .75). The Informational Utility subscale was strongly associated with empowerment and personal utility of GS. Correlations of the Emotional Utility subscale with psychosocial impact and anxiety and depression were weak to moderate. ConclusionInitial psychometric testing of the Adult Screening GENEtic Utility scale demonstrates its promise, and additional validation in translational genomics research is warranted.

C-reactive protein across pregnancy in individuals exposed to childhood maltreatment: The role of psychological and physical sequelae of maltreatment

BackgroundChildhood maltreatment (CM) has long-term consequences for the regulation of stress biology which are particularly pronounced when mental and physical health sequelae have manifested. C-reactive protein (CRP) has been shown to be elevated in the non-pregnant state in association with CM as well as in the setting of CM-associated mental and physical health sequelae. In pregnancy, however, the association between CM and CRP is less clear. We sought to examine this association and consider the moderating role of four common health sequelae of CM (maternal depressive symptoms, overweight/obesity, smoking, and hypertensive disorders during pregnancy). MethodsA prospective, longitudinal study of 744 healthy pregnant participants was conducted, with analyses focusing on a sample of 643 participants. CM was assessed with the Childhood Trauma Questionnaire (CTQ) and categorized by whether no vs. one or more moderate to severe CM experiences were reported. Blood serum concentrations of CRP, maternal depression severity (continuous scores of the Center for Epidemiologic Studies Depression Scale, CES-D) and smoking during pregnancy were assessed in early (16.52 ± 2.50 weeks gestation) and late (33.65 ± 1.18 weeks gestation) pregnancy. Pre-pregnancy body mass index (BMI) was obtained at the first study visit and hypertensive disorders diagnosed during pregnancy were obtained from the medical record. Linear mixed effects models were employed to assess main effects of CM as well as interactive effects of CM and four common CM-associated sequelae as well as a sum score of these sequelae on repeatedly measured CRP concentration. In secondary analyses, we conducted latent class analyses to classify participants based on their specific experiences of childhood abuse and/or neglect and to assess the association of these CM subgroups with CM sequelae and CRP. All analyses were adjusted for potential confounders (maternal race and ethnicity and education/income). ResultsCRP concentration decreased from early to late pregnancy (B = −0.06, SE = 0.01, p < 0.001). While there was no main effect of CM on CRP (p = 0.49), the interaction of CM and depressive symptoms was associated with CRP concentration (B = 0.08, SE = 0.04, p < 0.05), indicating higher CRP across pregnancy with increasing levels of depressive symptoms during pregnancy in participants with CM experience. This interaction was mainly driven by participants with co-occurring physical and emotional maltreatment. For none of the other CM-associated sequelae a statistically significant interaction with CM on CRP concentration was observed. ConclusionsThese results add to the growing empirical evidence suggesting higher inflammation during pregnancy in participants exposed to CM who experience depressive symptoms and highlight the detrimental effects of multiple co-occurring experiences of maltreatment. Given the negative consequences of chronic inflammatory state for the mother and the developing fetus, monitoring and treating psychiatric sequelae during pregnancy among participants exposed to CM is potentially an important opportunity to dampen long-term detrimental effects of CM, serving at least two generations.