A reliable and valid assessment of upper limb movement quality after stroke: the observational Drinking Task Assessment.

OBJECTIVE: To develop and evaluate the reliability and validity of a new observational Drinking Task Assessment (DTA) designed to assess quality of movement in task performance after stroke. DESIGN: Reliability and validity. METHODS: The DTA measures movement time and movement quality (smoothness, trunk, shoulder, elbow, and grasp movements) on a 4-level ordinal scale. Thirty participants with chronic stroke were assessed independently by 2 therapists. Intra-class correlation (ICC), standard error of measurement (SEM) and minimal real difference (MRD), weighted kappa, percentage of agreement, and Svensson method were used for reliability assessment. Motion capture-based kinematics and established clinical scales were used to evaluate validity. RESULTS: The absolute SEM and MRD for movement time were 0.4 and 1 s (11%), respectively. The ICC (≥ 0.93) and weighted kappa (0.71-1.0) showed good to excellent agreement for intra- and inter-rater reliability. DTA showed strong correlations with Fugl-Meyer Assessment (0.74), Action Research Arm Test (0.93), and kinematic measures of smoothness (0.93), trunk displacement (0.91), elbow extension (0.73), and shoulder movements (0.56), indicating good construct validity. CONCLUSIONS: The new DTA proved to be a reliable and valid tool for assessment of movement quality during task performance after stroke.

Lessons learned from a multimodal sensor-based eHealth approach for treating pediatric obsessive-compulsive disorder.

Introduction: The present study investigates the feasibility and usability of a sensor-based eHealth treatment in psychotherapy for pediatric obsessive-compulsive disorder (OCD), and explores the promises and pitfalls of this novel approach. With eHealth interventions, therapy can be delivered in a patient's home environment, leading to a more ecologically valid symptom assessment and access to experts even in rural areas. Furthermore, sensors can help indicate a patient's emotional and physical state during treatment. Finally, using sensors during exposure with response prevention (E/RP) can help individualize therapy and prevent avoidance behavior. Methods: In this study, we developed and subsequently evaluated a multimodal sensor-based eHealth intervention during 14 video sessions of cognitive-behavioral therapy (CBT) in 20 patients with OCD aged 12-18. During E/RP, we recorded eye movements and gaze direction via eye trackers, and an ECG chest strap captured heart rate (HR) to identify stress responses. Additionally, motion sensors detected approach and avoidance behavior. Results: The results indicate a promising application of sensor-supported therapy for pediatric OCD, such that the technology was well-accepted by the participants, and the therapeutic relationship was successfully established in the context of internet-based treatment. Patients, their parents, and the therapists all showed high levels of satisfaction with this form of therapy and rated the wearable approach in the home environment as helpful, with fewer OCD symptoms perceived at the end of the treatment. Discussion: The goal of this study was to gain a better understanding of the psychological and physiological processes that occur in pediatric patients during exposure-based online treatment. In addition, 10 key considerations in preparing and conducting sensor-supported CBT for children and adolescents with OCD are explored at the end of the article. This approach has the potential to overcome limitations in eHealth interventions by allowing the real-time transmission of objective data to therapists, once challenges regarding technical support and hardware and software usability are addressed. Clinical Trial Registration: www.ClinicalTrials.gov, identifier (NCT05291611).

[Telemedical Interventions in Ambulant Psychotherapeutic Practices: Online Survey of Psychotherapists and Patients in Germany on the use of Digital Interventions in Psychotherapy]. / Telemedizinische Interventionen in ambulanten psychotherapeutischen Praxen: deutschlandweite Online-Befragung von PsychotherapeutInnen und PatientInnen zur Nutzung digitaler Interventionen.

BACKGROUND: Psychotherapy is going digital. The study investigated the usage behavior and acceptance of digital psychotherapy interventions among outpatient psychotherapists and patients. METHOD: 269 therapists and 157 patients answered questions in an online survey on the use and satisfaction of digital psychotherapy interventions (video therapy, apps, VR, sensor-based psychotherapy), affinity for technology, acceptance of technology, digital therapy relationship. RESULTS: All participants were satisfied with video therapy, stated that they used apps, VR, etc. less. Patients were more open, more tech-savvy and felt more competent in their use compared to therapists. Psychotherapists rated the digital therapeutic relationship better than patients. DISCUSSION: The use of digital technologies in psychotherapy is not yet established in outpatient care. Measures to promote acceptance are necessary to break down barriers.

Impact of sinus surgery in people with cystic fibrosis and chronic rhinosinusitis in the era of highly effective modulator therapy: Protocol for a prospective observational study.

INTRODUCTION: Cystic fibrosis (CF) is commonly complicated by chronic rhinosinusitis (CRS). Despite highly effective management options, CRS in people with CF (PwCF+CRS) may be refractory to medical therapy, eventually requiring endoscopic sinus surgery. The impact of sinus surgery on pulmonary, quality of life (QOL), and other outcomes in PwCF+CRS in the expanding era of highly effective modulator therapy has not been fully elucidated. This study aims to determine if endoscopic sinus surgery can offer superior outcomes for PwCF+CRS when compared to continued medical treatment of CRS. METHODS AND ANALYSIS: This multi-institutional, observational, prospective cohort study will enroll 150 adults with PwCF+CRS across nine US CF Centers who failed initial medical therapy for CRS and elected to pursue either endoscopic sinus surgery or continue medical treatment. To determine if sinus surgery outperforms continued medical therapy in different outcomes, we will assess changes in pulmonary, CF-specific QOL, CRS-specific QOL, sleep quality, depression, headache, cognition, olfaction, productivity loss, and health utility value after treatment. The influence of highly effective modulator therapy on these outcomes will also be evaluated. This study will provide crucial insights into the impact of endoscopic sinus surgery for PwCF+CRS and aid with development of future treatment pathways and guidelines. ETHICS AND DISSEMINATION: This study has been approved by each institution's internal review board, and study enrollment began August 2019. Results will be disseminated in conferences and peer-reviewed journals. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04469439).

Rejoinder to the discussion on "LEAP: the latent exchangeability prior for borrowing information from historical data".

The discussions of our paper provide insights into the practical considerations of the latent exchangeability prior while also highlighting further extensions. In this rejoinder, we briefly summarize the discussions and provide comments.

LEAP: the latent exchangeability prior for borrowing information from historical data.

It is becoming increasingly popular to elicit informative priors on the basis of historical data. Popular existing priors, including the power prior, commensurate prior, and robust meta-analytic predictive prior, provide blanket discounting. Thus, if only a subset of participants in the historical data are exchangeable with the current data, these priors may not be appropriate. In order to combat this issue, propensity score approaches have been proposed. However, these approaches are only concerned with the covariate distribution, whereas exchangeability is typically assessed with parameters pertaining to the outcome. In this paper, we introduce the latent exchangeability prior (LEAP), where observations in the historical data are classified into exchangeable and non-exchangeable groups. The LEAP discounts the historical data by identifying the most relevant subjects from the historical data. We compare our proposed approach against alternative approaches in simulations and present a case study using our proposed prior to augment a control arm in a phase 3 clinical trial in plaque psoriasis with an unbalanced randomization scheme.

[18F]FDG PET/CT Imaging Is Associated with Lower In-Hospital Mortality in Patients with Pyogenic Spondylodiscitis-A Registry-Based Analysis of 29,362 Cases.

BACKGROUND: While MRI is the primary diagnostic tool for the diagnosis of spondylodiscitis, the role of [18F]-fluorodeoxyglucose ([18F]FDG) PET/CT is gaining prominence. This study aimed to determine the frequency of [18F]FDG PET/CT usage and its impact on the in-hospital mortality rate in patients with spondylodiscitis, particularly in the geriatric population. METHODS: We conducted a Germany-wide cross-sectional study from 2019 to 2021 using an open-access, Germany-wide database, analyzing cases with ICD-10 codes M46.2-, M46.3-, and M46.4- ('Osteomyelitis of vertebrae', 'Infection of intervertebral disc (pyogenic)', and 'Discitis unspecified'). Diagnostic modalities were compared for their association with in-hospital mortality, with a focus on [18F]FDG PET/CT. RESULTS: In total, 29,362 hospital admissions from 2019 to 2021 were analyzed. Of these, 60.1% were male and 39.9% were female, and 71.8% of the patients were aged 65 years and above. The overall in-hospital mortality rate was 6.5% for the entire cohort and 8.2% for the geriatric subgroup (p < 0.001). Contrast-enhanced (ce) MRI (48.1%) and native CT (39.4%) of the spine were the most frequently conducted diagnostic modalities. [18F]FDG PET/CT was performed in 2.7% of cases. CeCT was associated with increased in-hospital mortality (OR = 2.03, 95% CI: 1.90-2.17, p < 0.001). Cases with documented [18F]FDG PET/CT showed a lower frequency of in-hospital deaths (OR = 0.58, 95% CI: 0.18-0.50; p = 0.002). This finding was more pronounced in patients aged 65 and above (OR = 0.42, 95% CI: 0.27-0.65, p = 0.001). CONCLUSIONS: Despite its infrequent use, [18F]FDG PET/CT was associated with a lower in-hospital mortality rate in patients with spondylodiscitis, particularly in the geriatric cohort. This study is limited by only considering data on hospitalized patients and relying on the assumption of error-free coding. Further research is needed to optimize diagnostic approaches for spondylodiscitis.

Investigating Painkiller Use in Amateur Football: A Coach's Perspective.

BACKGROUND/OBJECTIVES: Painkiller use in amateur sports and, especially, in football is increasingly being discussed, but the scientific data on this field are very limited. Therefore, the aim of this study was to investigate the prevalence of painkiller use in amateur football from the perspective of coaches, as well as to determine how and to which extent coaches can influence their teams in terms of painkiller use and prevention. METHODS: Using an online questionnaire, a cross-sectional analysis of painkiller use in German amateur football from the 4th league to the lowest amateur classes was carried out from the perspective of team coaches. A total of 628 participants were contacted, and 400 (63.7%) completed the questionnaire completely and were therefore included in the evaluation. RESULTS: Of the 400 participating team coaches in amateur football, 369 (92.3%) were male and 31 (7.7%) were female. The coaches reported that 36.2% (SD = 29.1) of their players have used painkillers at some point due to football-related pain in their career. The majority of coaches believed that the use of painkillers is not compatible with competition (74%), and even more believed that it is not compatible with football training (90.8%). Furthermore, 56.2% of the coaches themselves had already taken painkillers in their own football career for football-related pain, and 64% had already bought over-the-counter painkillers without a prescription. The use of painkillers increased in the higher playing levels. The availability of painkillers in first aid kits was reported by around 60%, but they were reported as freely accessible in the dressing room by only 10% of the coaches. CONCLUSIONS: This is the first study to describe the painkiller use in amateur football from the perspective of coaches. The prevalence of painkiller use in this study was found to be significantly lower than what is indicated in the data from the existing literature. The majority of coaches see the use of painkillers during games and training as incompatible, even though there is a large proportion of coaches who have already bought over-the-counter painkillers for football-related pain. As the first scientific analysis of team coaches, this study provides fundamental data for the prevention of excessive painkiller use in amateur football.

The FRI classification - A new classification of fracture-related infections.

AIM: To identify the most relevant factors with respect to the management of fracture-related infection (FRI) and to develop a comprehensive FRI classification that guides decision-making and allows scientific comparison. METHOD: An international group of FRI experts determined the preconditions, purpose, primary factors for inclusion, format and detailed description of the elements of an FRI classification through a consensus driven process. RESULTS: Three major elements were identified and grouped together in the FRI Classification: Fracture (F), Related patient factors (R) and Impairment of soft tissues (I). Each element was divided into five levels of complexity. Fractures can be healed (F1) or unhealed (F2-5). Patients may be fully healthy (R1) or have 4 levels of compromise, with and without end-organ damage (R2-5). Soft tissue condition ranges from well vascularized and easily closed (I1) to major skin defects requiring free flaps (I4). In all three elements, the fifth level (F5, R5 or I5) describes a patient who has an unreconstructible bone, soft tissue envelope or is not fit for surgery. CONCLUSION: The FRI classification, which is based on the three major elements Fracture (F), Related patient factors (R) and Impairment of soft tissues (I) is intended to guide decision-making and improve the quality of scientific reporting for FRIs in the future. The proposed classification is based on expert opinion and therefore an essential next step is clinical validation, in order to realize the ultimate goal of improving outcomes in the management of FRI.

Predictors of Durable Remission After Successful Surgery for Cushing Disease: Results From the Multicenter RAPID Registry.

BACKGROUND AND OBJECTIVE: Cushing disease (CD) affects mortality and quality of life along with limited long-term remission, underscoring the need to better identify recurrence risk. The identification of surgical or imaging predictors for CD remission after transsphenoidal surgery has yielded some inconsistent results and has been limited by single-center, single-surgeon, or meta-analyses studies. We sought to evaluate the multicenter Registry of Adenomas of the Pituitary and Related Disorders (RAPID) database of academic US pituitary centers to assess whether robust nonhormonal recurrence predictors could be elucidated. METHODS: Patients with treated CD from 2011 to 2023 were included. The perioperative and long-term characteristics of CD patients with and without recurrence were assessed using univariable and multivariable analyses. RESULTS: Of 383 patients with CD from 26 surgeons achieving postoperative remission, 288 (75.2%) maintained remission at last follow-up while 95 (24.8%) showed recurrence (median time to recurrence 9.99 ± 1.34 years). Patients with recurrence required longer postoperative hospital stays (5 ± 3 vs 4 ± 2 days, P = .002), had larger average tumor volumes (1.76 ± 2.53 cm 3 vs 0.49 ± 1.17 cm 3 , P = .0001), and more often previously failed prior treatment (31.1% vs 14.9%, P = .001) mostly being prior surgery. Multivariable hazard prediction models for tumor recurrence found younger age (odds ratio [OR] = 0.95, P = .002) and Knosp grade of 0 (OR = 0.09, reference Knosp grade 4, P = .03) to be protective against recurrence. Comparison of Knosp grade 0 to 2 vs 3 to 4 showed that lower grades had reduced risk of recurrence (OR = 0.27, P = .04). Other factors such as length of stay, surgeon experience, prior tumor treatment, and Knosp grades 1, 2, or 3 failed to reach levels of statistical significance in multivariable analysis. CONCLUSION: This multicenter study centers suggests that the strongest predictors of recurrence include tumor size/invasion and age. This insight can help with patient counseling and prognostication. Long-term follow-up is necessary for patients, and early treatment of small tumors may improve outcomes.

Orientation Regulation of Class-switch Recombination in Human B Cells.

We developed a linear amplification-mediated high-throughput genome-wide translocation sequencing method to profile Ig class-switch recombination (CSR) in human B cells in an unbiased and quantitative manner. This enables us to characterize CSR junctions resulting from either deletional recombination or inversion for each Ig class/subclass. Our data showed that more than 90% of CSR junctions detected in peripheral blood in healthy control subjects were due to deletional recombination. We further identified two major CSR junction signatures/patterns in human B cells. Signature 1 consists of recombination junctions resulting from both IgG and IgA switching, with a dominance of Sµ-Sγ junctions (72%) and deletional recombination (87%). Signature 2 is contributed mainly by Sµ-Sα junctions (96%), and these junctions were almost all due to deletional recombination (99%) and were characterized by longer microhomologies. CSR junctions identified in healthy individuals can be assigned to both signatures but with a dominance of signature 1, whereas almost all CSR junctions found in patients with defects in DNA-PKcs or Artemis, two classical nonhomologous end joining (c-NHEJ) factors, align with signature 2. Thus, signature 1 may represent c-NHEJ activity during CSR, whereas signature 2 is associated with microhomology-mediated alternative end joining in the absence of the studied c-NHEJ factors. Our findings suggest that in human B cells, the efficiency of the c-NHEJ machinery and the features of switch regions are crucial for the regulation of CSR orientation. Finally, our high-throughput method can also be applied to study the mechanism of rare types of recombination, such as switching to IgD and locus suicide switching.

Feedstock variability impacts the bioconversion of sugar and lignin streams derived from corn stover by Clostridium tyrobutyricum and engineered Pseudomonas putida.

Feedstock variability represents a challenge in lignocellulosic biorefineries, as it can influence both lignocellulose deconstruction and microbial conversion processes for biofuels and biochemicals production. The impact of feedstock variability on microbial performance remains underexplored, and predictive tools for microbial behaviour are needed to mitigate risks in biorefinery scale-up. Here, twelve batches of corn stover were deconstructed via deacetylation, mechanical refining, and enzymatic hydrolysis to generate lignin-rich and sugar streams. These batches and their derived streams were characterised to identify their chemical components, and the streams were used as substrates for producing muconate and butyrate by engineered Pseudomonas putida and wildtype Clostridium tyrobutyricum, respectively. Bacterial performance (growth, product titers, yields, and productivities) differed among the batches, but no strong correlations were identified between feedstock composition and performance. To provide metabolic insights into the origin of these differences, we evaluated the effect of twenty-three isolated chemical components on these microbes, including three components in relevant bioprocess settings in bioreactors, and we found that growth-inhibitory concentrations were outside the ranges observed in the streams. Overall, this study generates a foundational dataset on P. putida and C. tyrobutyricum performance to enable future predictive models and underscores their resilience in effectively converting fluctuating lignocellulose-derived streams into bioproducts.

Development and validation of claims-based algorithms for estimating gestational age of spontaneous abortion and termination.

To study the risk of spontaneous abortion (SAB) or termination using healthcare utilization databases, algorithms to estimate the gestational age (GA) are needed. Using Medicaid data, we developed a hierarchical algorithm to classify pregnancy outcomes. We identified the subset of potential SAB and termination cases, and abstracted the GA from linked electronic medical records (gold standard). We developed three approaches: (1) assign median GA for SAB and termination cases in the US; (2) draw a random GA from the population distributions; (3) estimate GA based on regression models. Algorithm performance was assessed based on the proportion of pregnancies with estimated GA within 1-4 weeks of the gold standard, the mean squared error (MSE) and the R-squared. Approach 1 and Approach 3 had similar performance, though approach 3 using random forest models with variables selected via the Boruta algorithm had better MSE and R-squared. For SAB, 58.0% of pregnancies were correctly classified within 2 weeks of the gold standard (MSE: 8.7, R-squared: 0.09). For termination, the proportions were 66.3% (MSE: 11.7; R-squared: 0.35). SABs and terminations can be studied in healthcare utilization data with careful implementation of validated algorithms though higher level of GA misclassification is expected compared to live births.

Corrigendum: Abnormalities of thymic stroma may contribute to immune dysregulation in murine models of leaky severe combined immunodeficiency.

[This corrects the article DOI: 10.3389/fimmu.2011.00015.].

[Low UKA implantation volume, comorbidities, male sex, and implantation of constrained TKA are risk factors for septic revision after knee arthroplasty implantation : A register-based study from the German Arthroplasty Register]. / Geringes UKA-Implantationsvolumen, Komorbiditäten, männliches Geschlecht und die Implantation einer gekoppelten TKA sind Risikofaktoren für septische Revisionen nach Knieprothesenimplantation : Eine registerbasierte Studie aus dem Deutschen Endoprothesenregister (EPRD).

AIM: Periprosthetic joint infection (PJI) is one of the main causes of revision surgeries after total knee arthroplasty (TKA) and unicondylar knee replacement. Patient- and hospital-related risk factors must be evaluated to prevent PJI. This study identifies influencing factors and differences in infection rates between various types of implant. METHODS: The basis for the data is the German Arthroplasty Register (EPRD). Septic revisions were calculated with the aid of Kaplan-Meier estimates, with septic revision surgery defined as the primary endpoint. Patients with constrained and unconstrained TKA or UKA were analysed using the Holm multiple log-rank test and the Cox proportional hazard model. The 300,998 cases of knee arthroplasty analysed included 254,144 (84.4%) unconstrained TKA, 9993 (3.3%) constrained TKA and 36,861 (12.3%) UKA, with a maximum follow-up of 7 years. RESULTS: After 1 year, the PJI rate was 0.5% for UKA and 2.8% for TKA, whereas after 7 years it was 4.5% for UKA and 0.9% for TKA (p < 0.0001). In constrained TKA, the PJI rate was significantly increased compared with unconstrained TKA (p < 0.0001). After 1 year, the PJI rate was 2.0% for constrained TKA and 0.8% for unconstrained TKA, as well as 3.1% and 1.4% respectively after 7 years. Implantation of a constrained TKA (HR = 2.55), male sex (HR = 1.84), an increased Elixhauser Comorbidity Index score (HR = 1.18-1.56) and an implantation volume of less than 25 UKA per year (HR = 2.15) were identified as risk factors for revision surgeries; an Elixhauser Comorbidity Index score of 0 (HR = 0.80) was identified as a preventive factor. CONCLUSIONS: A reduced implantation volume and constrained knee arthroplasty are linked to a higher risk of PJI. Comorbidities (increased Elixhauser Comorbidity Index score), male sex and a low UKA-implantation volume were identified as risk factors for PJI. Patients who fulfil these criteria need specific infection prevention measures. Further analyses are required to investigate the potential influence of prevention and risk factor modification. LEVEL OF EVIDENCE: III.

Increased rate of injuries to the anterior cruciate ligament in amateur soccer players after the COVID-19 pandemic lockdown.

The COVID-19 pandemic led to the discontinuation of soccer activities at all levels of play. Injuries to the anterior cruciate ligament (ACL) are still one of the most severe injuries in soccer. The aim of this investigation was to analyze the changes in the incidence and mechanism of ACL injuries in professional and amateur soccer before and after the lockdown period. Injury data were prospectively collected using the database 'ACL registry in German soccer'. Between 2019 and 2021, 10 matches in professional, semi-professional, and amateur leagues before and after the lockdown were analyzed for the incidence and mechanism of ACL injuries. Data were collected using standardized and recently published study methods. Mean incidence of the 84 ACL injuries recorded during the study period was 0.083 injuries per 1000 h of exposure before and 0.079 injuries per 1000 h of exposure after the lockdown period (p = 0.699). In amateur soccer, the incidence of ACL injuries increased significantly from 0.058 injuries per 1000 h of exposure before to 0.128 injuries per 1000 h of exposure after the lockdown period (p = 0.026), in contrast to professional (p = 0.436) and semi-professional (p = 0.802) soccer. The predominant mechanisms of ACL injuries were non-contact injuries (pre-COVID: 59.1%; post-COVID: 57.7%) and indirect contact injuries (pre-COVID: 31.8%; post-COVID: 30.8%). The absence from training and match practice in German soccer during the COVID-19 lockdown led to a significantly increased ACL injury rate in amateur leagues, while in professional and semi-professional soccer no differences were reported. The mechanism of ACL injuries did not change after the lockdown period.Level of evidence: II.

Transcripts of repetitive DNA elements signal to block phagocytosis of hematopoietic stem cells.

Macrophages maintain hematopoietic stem cell (HSC) quality by assessing cell surface Calreticulin (Calr), an "eat-me" signal induced by reactive oxygen species (ROS). Using zebrafish genetics, we identified Beta-2-microglobulin (B2m) as a crucial "don't eat-me" signal on blood stem cells. A chemical screen revealed inducers of surface Calr that promoted HSC proliferation without triggering ROS or macrophage clearance. Whole-genome CRISPR-Cas9 screening showed that Toll-like receptor 3 (Tlr3) signaling regulated b2m expression. Targeting b2m or tlr3 reduced the HSC clonality. Elevated B2m levels correlated with high expression of repetitive element (RE) transcripts. Overall, our data suggest that RE-associated double-stranded RNA could interact with TLR3 to stimulate surface expression of B2m on hematopoietic stem and progenitor cells. These findings suggest that the balance of Calr and B2m regulates macrophage-HSC interactions and defines hematopoietic clonality.

Top speed sprinting: Thigh angular motion and eccentric hamstring strength in faster vs. slower sprinters.

Sprinting at maximum velocity requires fast angular motion of the thigh and effective hamstring function for optimum performance and injury prevention. In this cross-sectional investigation of 21 male sprinters, we acquired thigh angular kinematics while sprinting at top speed (range: 8.96-10.17 m/s), and then measured eccentric hamstring strength capacities using an isokinetic dynamometer during the same test session. In agreement with the hypotheses, thigh angular motion rates and the associated eccentric hamstring strength capacities were both significantly correlated with top speed (r-values: ∼0.5; p < 0.05). Additionally, when the participants were sorted by top speed, there were significant differences between the faster group and the slower group. Notably, on average the faster group showed faster thigh motion (angular acceleration: 10.3 kdeg/s2, 11 % greater than slower group) and higher eccentric hamstring strength capacities (peak moment: 2.26 Nm/kg, 14 % greater than slower group). This investigation indicates that fast thigh angular motion and eccentric hamstring strength are both important for sprint performance.