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Background: Historically, patients with metastatic renal cell carcinoma (mRCC) have been offered upfront cytoreductive nephrectomy (CN) followed by systemic therapy. Currently, CN is no longer the standard of care (SOC) based on the randomised phase 3 CARMENA study performed in the vascular endothelial growth factor receptor tyrosine kinase inhibitor era. With the advent of immune checkpoint inhibitor (ICI) combination therapy in first line, the role of CN needs to be reassessed. There is indirect evidence from small retrospective series that deferred CN after ICI combination therapy may lead to better outcomes. To reassess the role of CN, we designed PrimerX, a randomised controlled trial following the Trial within Cohorts (TwiCs) study design. The primary objective of this study is to re-evaluate the benefit of deferred local treatment in the current era of immunotherapy. Study design: This PrimerX study has been designed as a TwiCs study within the Dutch Prospective Renal Cell Carcinoma (PRO-RCC) cohort. The PRO-RCC cohort includes patients with mRCC and nonmetastatic RCC, and has been set up for prospective collection of long-term clinical data and as an infrastructure for initiating TwiCs studies. The PrimerX TwiCs trial follows a Bayesian adaptive multistage design to allow for early discontinuation due to futility or efficacy. PrimerX has appropriate ethics approval and is registered at clinical.trials.gov (NCT05941169). End points: The primary clinical endpoint is overall survival, defined as the time from randomisation to death from any cause. The secondary endpoint is the objective response rate within the primary tumour prior to local therapy, as assessed by a computed tomography scan. Patients and methods: A maximum of 700 patients with synchronous mRCC and absence of progression at metastatic sites following at least 6 mo of standard first-line ICI combination therapy will be assigned randomly to receive local treatment of the primary tumour (experimental arm) or SOC (control arm). The experimental intervention consists of (partial) CN, any form of ablative local therapy, or magnetic resonance imaging guided ablative stereotactic radiotherapy, performed within 6 mo and 1.5 yr after the start of systemic treatment.

Background and objective: While programmes such as the European Basic Laparoscopic Urological Skills have made strides in foundational training, a significant gap exists for intermediate and advanced laparoscopy education. Our objective is to develop and validate the European laparoscopic intermediate urological skills (LUSs2) curriculum, which will establish uniformity in the training of urological laparoscopic procedures and facilitate proficiency among practitioners. Methods: The study combines a literature review, cognitive task analysis development by a steering group, and a two-round Delphi survey involving international experts in urological laparoscopy. Consensus was defined as agreement of ≥70% among experts. The survey included statements on various laparoscopic procedures, assessed on a Likert scale from 1 (strongly disagree) to 9 (strongly agree). Key findings and limitations: The Delphi process achieved consensus on 85% (235/275) of statements, indicating a strong agreement on the curriculum’s content. Areas covered include renal hilum dissection, major vessel injury management, enucleation and renorrhaphy, vesicourethral anastomosis, and pyeloplasty. Limitations include the nonsystematic nature of the literature review and potential biases inherent in expert-based consensus methods. Conclusions and clinical implications: The LUSs2 curriculum significantly advances the standardised training of laparoscopic urological skills. It offers a detailed, consensus-validated framework that addresses the need for uniformity in surgical education and aims to enhance surgical proficiency and patient care. Patient summary: This study presents the development of a new standardised training curriculum for urological laparoscopic surgery. We intend this curriculum to improve the quality of surgical training and ensure high-quality patient care.

Students in vocational education and training (VET) need to be prepared for coping with value conflicts they will face in their professional lives. Development of awareness of one's feelings is an essential aspect in this regard. Students need to be aware of their own inner feelings to decrease the unconscious influence of inner feelings on their actions in a value conflict. The purpose of this study is to contribute to a theoretical and practical basis for the design of affective learning experiences aimed to elicit VET students' receptivity to inner self-exploration of their feelings and values. Students were put in an affective learning experience. Three groups of first- and second-year VET students (N = 36) participated in the affective learning experience. Most students did start to self-explore their feelings. However, our findings showed that they did not arrive at affective perceptual awareness. According to the students, deepening inner self-exploration into one's own feelings and values can be stimulated by paying explicit attention to inner feelings, concrete instructions, room for reciprocal exchanges between students and the teacher's participation in sharing inner feelings.

Immunological dysregulation plays a fundamental role in the inflammatory aspects of endometriosis. Circulating blood leukocytes, one of the most abundant immune cell populations in the human body, have been shown diagnostic significance in some diseases. Nevertheless, the association between peripheral blood leukocyte counts and endometriosis remains unexplored to date. We analyzed two targeted study cohorts: a tertiary center cohort (Endometriosis at Oxford University (ENDOX) Study: 325 cases/177 controls) and a large-scale population study (UK Biobank (UKBB): 1537 cases/6331 controls). In both datasets, peripheral venous blood sample results were retrieved, and counts of leukocyte subpopulations, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils, were analyzed. Logistic regression models were used to investigate the association of leukocyte subtype alterations with endometriosis status, adjusting for confounding factors. We demonstrate that a higher blood basophil level is associated with increased odds of endometriosis. This association was first discovered in the ENDOX cohort (basophils >0.04 × 109/L: OR 1.65 (95% CI: 1.06–2.57), Ptrend = 0.025) and replicated in the UKBB dataset (basophils >0.04 × 109/L: OR 1.26 (95% CI: 1.09–1.45), Ptrend = 0.001). Notably, women with basophil counts in the upper tercile had significantly increased odds of having stage III/IV endometriosis (ENDOX study: OR = 2.30, 95% CI (1.25–4.22), Ptrend = 0.007; UKBB study (OR = 1.40, 95% CI (1.07–1.85), Ptrend = 0.015). None of the other leukocyte subtypes showed an association. Our findings suggest an association between inflammatory responses and the pathogenesis of endometriosis; future studies are warranted to investigate whether the association is causal.

Learning to become aware of one's own values to be able to cope with value conflicts is an important part of a higher vocational education curriculum. Higher vocational education teachers are used to offering cognitive learning experiences to students to teach them how to deal with value conflicts, disregarding the affective aspect of values. In this qualitative study, we argue that inter-affective learning experiences are needed to encourage students to deal with value conflicts through affective involvement. We had two research questions: (1) How do teachers and students reflect on an inter-affective learning experience that aims to promote interactive affective sharing of a value conflict? and (2) What should characterize guidance for inter-affective learning experiences aimed at promoting interactive affective sharing of a value conflict? The research was carried out at a Dutch University of Applied Science offering higher vocational education programs. Four groups of teachers and two groups of students participated in an inter-affective learning experience about a value conflict, followed by a focus group discussion on the experience with group members. Teachers and students agreed that they need support in learning to sense their own experience of inner feelings. The reflections led to recommendations for guiding students' inter-affective learning experiences to encourage affective involvement in a value conflict.

INTRODUCTION: It would be valuable if home-based rehabilitation training technologies could automatically assess arm impairment after stroke. Here, we tested whether a simple measure-the repetition rate (or rep rate) when performing specific exercises as measured with simple sensors-can be used to estimate Upper Extremity Fugl-Meyer (UEFM) score. METHODS: 41 individuals with arm impairment after stroke performed 12 sensor-guided exercises under therapist supervision using a commercial sensor system comprised of two pucks that use force and motion sensing to measure the start and end of each exercise repetition. 14 of these participants then used the system at home for three weeks. RESULTS: Using linear regression, UEFM score was well estimated using the rep rate of one forward-reaching exercise from the set of 12 exercises (r2 = 0.75); this exercise required participants to alternately tap pucks spaced about 20 cm apart (one proximal, one distal) on a table in front of them. UEFM score was even better predicted using an exponential model and forward-reaching rep rate (Leave One Out Cross Validation (LOOCV) r2 = 0.83). We also tested the ability of a nonlinear, multivariate model (a regression tree) to predict UEFM, but such a model did not improve prediction (LOOCV r2 = 0.72). However, the optimal decision tree also used the forward-reaching task along with a pinch grip task to subdivide more and less impaired patients in a way consistent with clinical intuition. At home, rep rate for the forward-reaching exercise well predicted UEFM score using an exponential model (LOOCV r2 = 0.69), but only after we re-estimated coefficients using the home data. DISCUSSION: These results show how a simple measure-exercise rep rate measured with simple sensors-can be used to infer an arm impairment score and suggest that prediction models should be tuned separately for the clinic and home environments.

Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Herein, we characterize variation in DNA methylation (DNAm) and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genotype data and methylation in endometrial samples from 984 deeply-phenotyped participants. We estimate that 15.4% of the variation in endometriosis is captured by DNAm and identify significant differences in DNAm profiles associated with stage III/IV endometriosis, endometriosis sub-phenotypes and menstrual cycle phase, including opening of the window for embryo implantation. Menstrual cycle phase was a major source of DNAm variation suggesting cellular and hormonally-driven changes across the cycle can regulate genes and pathways responsible for endometrial physiology and function. DNAm quantitative trait locus (mQTL) analysis identified 118,185 independent cis-mQTLs including 51 associated with risk of endometriosis, highlighting candidate genes contributing to disease risk. Our work provides functional evidence for epigenetic targets contributing to endometriosis risk and pathogenesis. Data generated serve as a valuable resource for understanding tissue-specific effects of methylation on endometrial biology in health and disease.

BackgroundUpper extremity (UE) stroke rehabilitation requires patients to perform exercises at home, yet patients show limited benefit from paper-based home exercise programs.ObjectiveTo compare the effectiveness of 2 home exercise programs for reducing UE impairment: a paper-based approach and a sensorized exercise system that incorporates recommended design features for home rehabilitation technology.MethodsIn this single-blind, randomized controlled trial, 27 participants in the subacute phase of stroke were assigned to the sensorized exercise (n = 14) or conventional therapy group (n = 13), though 2 participants in the conventional therapy group were lost to follow-up. Participants were instructed to perform self-guided movement training at home for at least 3 hours/week for 3 consecutive weeks. The sensorized exercise group used FitMi, a computer game with 2 puck-like sensors that encourages movement intensity and auto-progresses users through 40 exercises. The conventional group used a paper book of exercises. The primary outcome measure was the change in Upper Extremity Fugl-Meyer (UEFM) score from baseline to follow-up. Secondary measures included the Modified Ashworth Scale for spasticity (MAS) and the Visual Analog Pain (VAP) scale.ResultsParticipants who used FitMi improved by an average of 8.0 ± 4.6 points on the UEFM scale compared to 3.0 ± 6.1 points for the conventional participants, a significant difference (t-test, P = .029). FitMi participants exhibited no significant changes in UE MAS or VAP scores.ConclusionsA sensor-based exercise system incorporating a suite of recommended design features significantly and safely reduced UE impairment compared to a paper-based, home exercise program.Trial registrationClinicalTrials.gov Identifier: NCT03503617.

Home-based exercises are an important component of stroke rehabilitation but are seldom fully completed. Past studies of exercise perseverance in the general public have suggested the importance of early exercise frequency and schedule consistency (in terms of which days of the week exercises are performed) because they encourage habit formation. To test whether these observations apply after a stroke, we leveraged data from 2,583 users of a sensor-based system (FitMi) developed to motivate movement exercises at home. We grouped users based on their early exercise frequency (defined across the initial 6 weeks of use) and calculated the evolution of habit score (defined as exercise frequency multiplied by exercise duration) across 6 months. We found that habit score decayed exponentially over time but with a slower decay constant for individuals with higher early frequency. Only the group with an early exercise frequency of 4 days/week or more had non-zero habit score at six months. Within each frequency group, dividing individuals into higher and lower consistency subgroups revealed that the higher consistency subgroups had significantly higher habit scores. These results are consistent with previous studies on habit formation in exercise and may help in designing effective home rehabilitation programs after stroke.

Abstract Background In stroke rehabilitation, wearable technology can be used as an intervention modality by providing timely, meaningful feedback on motor performance. Stroke survivors’ preferences may offer a unique perspective on what metrics are intuitive, actionable, and meaningful to change behavior. However, few studies have identified feedback preferences from stroke survivors. This project aims to determine the ease of understanding and movement encouragement of feedback based on wearable sensor data (both arm/hand use and mobility) for stroke survivors and to identify preferences for feedback metrics (mode, content, frequency, and timing). Methods A sample of 30 chronic stroke survivors wore a multi-sensor system in the natural environment over a 1-week monitoring period. The sensor system captured time in active movement of each arm, arm use ratio, step counts and stance time symmetry. Using the data from the monitoring period, participants were presented with a movement report with visual displays of feedback about arm/hand use, step counts and gait symmetry. A survey and qualitative interview were used to assess ease of understanding, actionability and components of feedback that users found most meaningful to drive lasting behavior change. Results Arm/hand use and mobility sensor-derived feedback metrics were easy to understand and actionable. The preferred metric to encourage arm/hand use was the hourly arm use bar plot, and similarly the preferred metric to encourage mobility was the hourly steps bar plot, which were each ranked as top choice by 40% of participants. Participants perceived that quantitative (i.e., step counts) and qualitative (i.e., stance time symmetry) mobility metrics provided complementary information. Three main themes emerged from the qualitative analysis: (1) Motivation for behavior change, (2) Real-time feedback based on individual goals, and (3) Value of experienced clinicians for prescription and accountability. Participants stressed the importance of having feedback tailored to their own personalized goals and receiving guidance from clinicians on strategies to progress and increase functional movement behavior in the unsupervised home and community setting. Conclusion The resulting technology has the potential to integrate engineering and personalized rehabilitation to maximize participation in meaningful life activities outside clinical settings in a less structured environment.

Arm movement recovery after stroke can improve with sufficient exercise. However, rehabilitation therapy sessions are typically not enough. To address the need for effective methods of increasing arm exercise outside therapy sessions we developed a novel armrest, called Boost. It easily attaches to a standard manual wheelchair just like a conventional armrest and enables users to exercise their arm in a linear forward-back motion. This paper provides a detailed design description of Boost, the biomechanical analysis method to evaluate the joint torques required to operate it, and the results of pilot testing with five stroke patients. Biomechanics results show the required shoulder flexion and elbow extension torques range from -25% to +36% of the torques required to propel a standard pushrim wheelchair, depending on the direction of applied force. In pilot testing, all five participants were able to exercise the arm with Boost in stationary mode (with lower physical demand). Three achieved overground ambulation (with higher physical demand) exceeding 2 m/s after 2-5 practice trials; two of these could not propel their wheelchair with the pushrim. This simple to use, dynamic armrest provides people with hemiparesis a way to access repetitive arm exercise outside of therapy sessions, independently right in their wheelchair. Significantly, Boost removes the requirements to reach, grip, and release the pushrim to propel a wheelchair, an action many individuals with stroke cannot complete.

Persevering with home rehabilitation exercise is a struggle for millions of people in the US each year. A key factor that may influence motivation to engage with rehabilitation exercise is the challenge level of the assigned exercises, but this hypothesis is currently supported only by subjective, self-report. Here, we studied the relationship between challenge level and perseverance using long-term, self-determined exercise patterns of a large number of individuals (N = 2,581) engaging in home rehabilitation with a sensor-based exercise system without formal supervision. FitMi is comprised of two puck-like sensors and a library of 40 gamified exercises for the hands, arms, trunk, and legs that are designed for people recovering from a stroke. We found that individuals showed the greatest perseverance with the system over a 2-month period if they had (1) a moderate level of motor impairment and (2) high but not perfect success during the 1st week at completing the exercise game. Further, a steady usage pattern (vs. accelerating or decelerating use) was associated with more overall exercise, and declines in exercise amount over time were associated with exponentially declining session initiation probability rather than decreasing amounts of exercise once a session was initiated. These findings confirm that an optimized challenge level and regular initiation of exercise sessions predict achievement of a greater amount of overall rehabilitation exercise in a group of users of commercial home rehabilitation technology and suggest how home rehabilitation programs and exercise technologies can be optimized to promote perseverance.

ObjectiveMany patients with subacute stroke rely on the nonparetic arm and leg to propel manual wheelchairs. We designed a bimanual, lever-driven wheelchair (LARA) to promote overground mobility and hemiparetic arm exercise. This study measured the feasibility of using LARA to increase arm movement, achieve mobility, and improve arm motor recovery (clinicaltrials.gov/ct2/show/NCT02830893).DesignRandomized, assessor-blind, controlled trial.SettingTwo inpatient rehabilitation facilities.SubjectsNineteen patients with subacute stroke (1 week to 2 months post-stroke) received 30 minutes extra arm movement practice daily, while admitted to inpatient rehabilitation (n = 10) or before enrollment in outpatient therapy (n = 9).InterventionsPatients were randomized to train with the LARA wheelchair (n = 11) or conventional exercises with a rehabilitation therapist (n = 8).Main measuresNumber of arm movements per training session; overground speed; Upper Extremity Fugl-Meyer score at three-month follow-up.ResultsParticipants who trained with LARA completed 254 (median) arm movements with the paretic arm each session. For three participants, LARA enabled wheelchair mobility at practical indoor speeds (0.15-0.30 m/s). Fugl-Meyer score increased 19 ± 13 points for patients who trained with LARA compared to 14 ± 7 points with conventional exercises (P = 0.32). Secondary measures including shoulder pain and increased tone did not differ between groups. Mixed model analysis found significant interaction between LARA training and treatment duration (P = 0.037), informing power analysis for future investigation.ConclusionsPractising arm movement with a lever-driven wheelchair is a feasible method for increasing arm movement early after stroke. It enabled wheelchair mobility for a subset of patients and shows potential for improving arm motor recovery.

Abstract Background There is inconsistency in outcomes collected in renal cell cancer (RCC) intervention effectiveness studies and variability in their definitions. This makes critical summaries of the evidence base difficult and sub‐optimally informative for clinical practice guidelines and decision‐making by patients and healthcare professionals. A solution is to develop a core outcome set (COS), an agreed minimum set of outcomes to be reported in all trials in a clinical area. Objectives To develop three COS for (a) localised, (b) locally advanced and (c) metastatic RCC study design, participants and methods The methods are the same for each of our three COS and are structured in two phases. Phase 1 identifies potentially relevant outcomes by conducting both a systematic literature review and patient interviews (N ~ 30 patients). Qualitative data will be analysed using framework analysis. In phase 2, all outcomes identified in phase 1 will be entered in a modified eDelphi, whereby patients and healthcare professionals (50 of each) will score each outcome's importance (Likert scale from 1 [not important] to 9 [critically important]). Outcomes scored in the 7–9 range by ≥70% and 1–3 by ≤15% will be regarded as ‘consensus in’, and the vice versa of this will constitute ‘consensus out’. All other combinations will be regarded as equivocal and discussed at consensus meetings (including 10 patients and 10 healthcare professionals) in order to vote on them and ratify the results of the eDelphi. Discussion The R‐COS will reduce outcome reporting heterogeneity and improve the evidence base for RCC. Study registration The study is registered with the COMET initiative: https://www.comet-initiative.org/studies/details/1406.

Background: Upfront cytoreductive nephrectomy (CN) is no longer the standard of care for patients with metastastic renal cell carcinoma (mRCC) with intermediate or poor prognosis according to the International mRCC Database Consortium categories. Objective: To investigate indications for CN following first-line ipilimumab-nivolumab, and assess management and outcomes for patients achieving no evidence of disease (NED) after CN. Design, setting, and participants: This was a retrospective cohort study among 125 patients with synchronous mRCC who received ipilimumab-nivolumab treatment between March 2019 and June 2022 at four European centres. At one of the four centres, nivolumab was stopped following NED. Outcome measurements and statistical analysis: We measured complete response of metastases (mCR) according to Response Evaluation Criteria in Solid Tumours 1.1; near-complete response of mestastases (mnCR) was defined as a >80% reduction in cumulative metastatic volume. Treatment-free survival (TFS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS) were determined. Results and limitations: At median follow-up of 25 mo, 23/125 patients (18%) had undergone deferred CN. Of 26 patients (21%) with mCR or mnCR, 19 (73%) underwent CN to achieve NED, of whom 11 (58%) discontinued nivolumab, with median TFS of 21 mo. For patients who continued (n = 8, 42%) versus discontinued nivolumab following NED, 2-yr DFS was 83% versus 60% (p = 0.675) and 3-yr CSS was 100% versus 70% (p = 0.325). Four patients underwent CN because of a dissociated response of the primary tumour and were still alive at median follow-up of 5 mo. Conclusions: CN can result in NED, durable DFS, and substantial time off systemic therapy. More collaborative data are required to ascertain the benefits of treatment discontinuation versus oncologic safety. Patient summary: In our study using real-world data, 18% of patients treated with immunotherapy underwent deferred kidney surgery. The majority were free of disease after 3 years. Half of the patients who stopped immunotherapy after surgery have been off therapy for 21 months or longer. Larger studies are needed to investigate the effect of kidney surgery and discontinuation of immunotherapy on survival.

Abstract Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Herein, we characterize variation in DNA methylation (DNAm) and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genotype data and methylation in endometrial samples from 984 deeply-phenotyped participants. We estimate that 15.4% of the variation in endometriosis is captured by DNAm and identify significant differences in DNAm profiles associated with stage III/IV endometriosis, endometriosis sub-phenotypes and menstrual cycle phase, including opening of the window for embryo implantation. Menstrual cycle phase was a major source of DNAm variation suggesting cellular and hormonally-driven changes across the cycle can regulate genes and pathways responsible for endometrial physiology and function. DNAm quantitative trait locus (mQTL) analysis identified 118,185 independent cis-mQTLs including 51 associated with risk of endometriosis, highlighting candidate genes contributing to disease risk. Our work provides functional evidence for epigenetic targets contributing to endometriosis risk and pathogenesis. Data generated serve as a valuable resource for understanding tissue-specific effects of methylation on endometrial biology in health and disease.

Abstract Background Ongoing research in the field of both localized, locally advanced and metastatic renal cell carcinoma has resulted in the availability of multiple treatment options. Hence, many questions are still unanswered and await further research. A nationwide collaborative registry allows to collect corresponding data. For this purpose, the Dutch PROspective Renal Cell Carcinoma cohort (PRO-RCC) has been founded, for the prospective collection of long-term clinical data, patient reported outcome measures (PROMs) and patient reported experience measures (PREMs). Methods PRO-RCC is designed as a multicenter cohort for all Dutch patients with renal cell carcinoma (RCC). Recruitment will start in the Netherlands in 2023. Importantly, participants may also consent to participation in a ‘Trial within cohorts’ studies (TwiCs). The TwiCs design provides a method to perform (randomized) interventional studies within the registry. The clinical data collection is embedded in the Netherlands Cancer Registry (NCR). Next to the standardly available data on RCC, additional clinical data will be collected. PROMS entail Health-Related Quality of Life (HRQoL), symptom monitoring with optional ecological momentary assessment (EMA) of pain and fatigue, and optional return to work- and/or nutrition questionnaires. PREMS entail satisfaction with care. Both PROMS and PREMS are collected through the PROFILES registry and are accessible for the patient and the treating physician. Trial registration Ethical board approval has been obtained (2021_218) and the study has been registered at ClinicalTrials.gov (NCT05326620). Discussion PRO-RCC is a nationwide long-term cohort for the collection of real-world clinical data, PROMS and PREMS. By facilitating an infrastructure for the collection of prospective data on RCC, PRO-RCC will contribute to observational research in a real-world study population and prove effectiveness in daily clinical practice. The infrastructure of this cohort also enables that interventional studies can be conducted with the TwiCs design, without the disadvantages of classic RCTs such as slow patient accrual and risk of dropping out after randomization.

Abstract Objectives To analyse variation in clinical management of cT1 renal cell carcinoma (RCC) in the Netherlands related to surgical hospital volume (HV). Materials and methods Patients diagnosed with cT1 RCC during 2014–2020 were identified in the Netherlands Cancer Registry. Patient and tumour characteristics were retrieved. Hospitals performing kidney cancer surgery were categorised by annual HV as low (HV 50). Trends over time in nephron‐sparing strategies for cT1a and cT1b were evaluated. Patient, tumour and treatment characteristics of (partial) nephrectomies were compared by HV. Variation in applied treatment was studied by HV. Results Between 2014 and 2020, 10 964 patients were diagnosed with cT1 RCC. Over time, a clear increase in nephron‐sparing management was observed. The majority of cT1a underwent a partial nephrectomy (PN), although less PNs were applied over time (from 48% in 2014 to 41% in 2020). Active surveillance (AS) was increasingly applied (from 18% to 32%). For cT1a, 85% received nephron‐sparing management in all HV categories, either with AS, PN or focal therapy (FT). For T1b, radical nephrectomy (RN) remained the most common treatment (from 57% to 50%). Patients in high‐volume hospitals underwent more often PN (35%) for T1b compared with medium HV (28%) and low HV (19%). Conclusion HV is related to variation in the management of cT1 RCC in the Netherlands. The EAU guidelines have recommended PN as preferred treatment for cT1 RCC. In most patients with cT1a, nephron‐sparing management was applied in all HV categories, although differences in applied strategy were found and PN was more frequently used in high HV. For T1b, high HV was associated with less appliance of RN, whereas PN was increasingly used. Therefore, closer guideline adherence was found in high‐volume hospitals.

Adherence to home exercise programs (HEPs) during physical rehabilitation is usually unmonitored and is thought to be low from self-reports. This article describes exploratory implementation of a Sensor Enhanced Activity Management (SEAM) system that combines HEP management software with a movement sensor for monitoring and motivating HEP adherence. The article also presents results from attempting to gain reimbursement for home use of the system with therapist oversight using Remote Physiologic Monitoring (RPM) codes. Four therapists used the system in their regular practice during the first six months of the COVID-19 pandemic. Therapists filled out surveys, kept notes, and participated in interviews. Billing and reimbursement data were obtained from the treatment facility. Exercise data from the SEAM system were used to understand HEP adherence. Patients were active for a mean of 40% (26% SD) of prescribed days and completed a mean of 25% (25% SD) of prescribed exercises. The therapists billed 23 RPM codes (USD 2353), and payers reimbursed eight of those instances (USD 649.21). The therapists reported that remote monitoring and the use of a physical movement sensor was motivating to their patients and increased adherence. Sustained technical support for therapists will likely improve implementation of new remote monitoring and treatment systems. RPM codes may enable reimbursement for review and program management activities, but, despite COVID-19 CMS waivers, organizations may have more success if these services are billed under supervision of a physician.

Prior studies have indicated that prosocial behavior might be a protective factor for developing internalizing and externalizing behavioral problems. However, little research has been conducted on within-person changes of prosocial behavior and behavioral problems over time. With random-intercept cross-lagged panel models (RI-CLPMs), the current study analyzed longitudinal associations between prosocial behavior and behavioral problems in two twin cohorts (98% Western European): in early childhood (age M = 4.77, SD = .58, 52% girls, N = 440) and middle childhood (age M = 7.94, SD = .67, 51% girls, N = 512). To obtain robust results, two parental reported questionnaires and an observational task were used as prosocial behavior assessments. In line with the literature, we found a significant between-person association between externalizing behavior and parent reported prosocial behavior in middle childhood, but not in early childhood. Some evidence indicated that changes in externalizing problems affect later prosocial behavior in middle childhood. Overall, however, the RI-CLPMs provided most support for the hypothesis that within-person changes in prosocial behavior are not related to within-person changes in behavioral problems. Thus, our findings did not support the hypothesis that increased prosocial behavior directly results in decreased behavioral problems, but emphasizes the need to take into account the multifaceted nature of prosocial behavior.

Miscarriage is a common, complex trait affecting ~15% of clinically confirmed pregnancies. Here we present the results of large-scale genetic association analyses with 69,054 cases from five different ancestries for sporadic miscarriage, 750 cases of European ancestry for multiple (≥3) consecutive miscarriage, and up to 359,469 female controls. We identify one genome-wide significant association (rs146350366, minor allele frequency (MAF) 1.2%, P = 3.2 × 10-8, odds ratio (OR) = 1.4) for sporadic miscarriage in our European ancestry meta-analysis and three genome-wide significant associations for multiple consecutive miscarriage (rs7859844, MAF = 6.4%, P = 1.3 × 10-8, OR = 1.7; rs143445068, MAF = 0.8%, P = 5.2 × 10-9, OR = 3.4; rs183453668, MAF = 0.5%, P = 2.8 × 10-8, OR = 3.8). We further investigate the genetic architecture of miscarriage with biobank-scale Mendelian randomization, heritability, and genetic correlation analyses. Our results show that miscarriage etiopathogenesis is partly driven by genetic variation potentially related to placental biology, and illustrate the utility of large-scale biobank data for understanding this pregnancy complication.

Numerous societal trends are compelling a transition from inpatient to outpatient venues of care for medical rehabilitation. While there are advantages to outpatient rehabilitation (e.g., lower cost, more relevant to home and community function), there are also challenges including lack of information about how patient progress observed in the outpatient clinic translates into improved functional performance at home. At present, outpatient providers must rely on patient-reported information about functional progress (or lack thereof) at home and in the community. Information and communication technologies (ICT) offer another option-data collected about the patient's adherence, performance and progress made on home exercises could be used to help guide course corrections between clinic visits, enhancing effectiveness and efficiency of outpatient care. In this article, we describe our efforts to explore use of sensor-enhanced home exercise and big data analytics in medical rehabilitation. The goal of this work is to demonstrate how sensor-enhanced exercise can improve rehabilitation outcomes for patients with significant neurological impairment (e.g., from stroke, traumatic brain injury, and spinal cord injury). We provide an overview of big data analysis and explain how it may be used to optimize outpatient rehabilitation, creating a more efficient model of care. We describe our planned development efforts to build advanced analytic tools to guide home-based rehabilitation and our proposed randomized trial to evaluate effectiveness and implementation of this approach.

Many genetic factors that contribute to uterine leiomyomata (UL) - the most common tumours of the female genital tract - remain to be discovered. Here, the authors conduct a UL meta-genome-wide association study, and find loci related to altered muscle tissue biology that are associated with UL.

Context: Outcomes in renal cell carcinoma (RCC) are reported inconsistently, with variability in definitions and measurement. Hence, it is difficult to compare intervention effectiveness and synthesise outcomes for systematic reviews and to create clinical practice guidelines. This uncertainty in the evidence makes it difficult to guide patient-clinician decision-making. One solution is a core outcome set (COS): an agreed minimum set of outcomes. Objective: To describe outcome reporting, definitions, and measurement heterogeneity as the first stage in co-creating a COS for localised renal cancer. Evidence acquisition: We systematically reviewed outcome reporting heterogeneity in effectiveness trials and observational studies in localised RCC. In total, 2822 studies (randomised controlled trials, cohort studies, case-control studies, systematic reviews) up to June 2020 meeting our inclusion criteria were identified. Abstracts and full texts were screened independently by two reviewers; in cases of disagreement, a third reviewer arbitrated. Data extractions were double-checked. Evidence synthesis: We included 149 studies and found that there was inconsistency in which outcomes were reported across studies and variability in the definitions used for outcomes that were conceptually the same. We structured our analysis using the outcome classification taxonomy proposed by Dodd et al. Outcomes linked to adverse events (eg, bleeding, outcomes linked to surgery) and renal injury outcomes (reduced renal function) were reported most commonly. Outcomes related to deaths from any cause and from cancer were reported in 44% and 25% of studies, respectively, although the time point for measurement and the analysis methods were inconsistent. Outcomes linked to life impact (eg, global quality of life) were reported least often. Clinician-reported outcomes are more frequently reported than patient-reported outcomes in the renal cancer literature. Conclusions: This systematic review underscores the heterogeneity of outcome reporting, definitions, and measurement in research on localised renal cancer. It catalogues the variety of outcomes and serves as a first step towards the development of a COS for localised renal cancer. Patient summary: We reviewed studies on localised kidney cancer and found that multiple terms and definitions have been used to describe outcomes. These are not defined consistently, and often not defined at all. Our review is the first phase in developing a core outcome set to allow better comparisons of studies to improve medical care.

Endometriosis is a chronic condition that affects ~10% of women globally. Its symptoms include chronic pelvic pain, heavy periods and tiredness/fatigue, which have been associated with poorer quality of life and mental health. We aim to explore the impact of the COVID-19 pandemic on pain and fatigue symptoms and their interactions with the impact on mental health in people with endometriosis. This global cross-sectional online survey study collected data from 4717 adults with self-reported surgical/radiological diagnosis of endometriosis between May and June 2020. The survey included questions on the current status and changes of endometriosis symptoms (pelvic pain, tiredness/fatigue, and bleeding patterns), mental health, pain catastrophising, and the impact of the COVID-19 pandemic on the respondents’ lives. Compared to 6 months earlier, Respondents reported a marked worsening of their endometriosis symptoms (endometriosis-associated pain (39.3%; 95% CI: 37.7, 40.5), tiredness/fatigue (49.9%; 95% CI: 48.4, 51.2) and bleeding patterns (39.6%; 95% CI: 38.2, 41)) and mental health (38.6%; 95% CI: 37.2, 39.9). Those with a pre-existing mental health diagnosis (38.8%) were more likely to report their symptoms worsening. Worsening of pain and tiredness/fatigue was significantly correlated with worsening of mental health (P < 0.001). The relationship between changes in mental health and (a) change in pain and (b) change in fatigue was found to be weakly mediated by pain catastrophising scores (pain: B = 0.071, lower limit of confidence interval (LLCI) = 0.060, upper limit of confidence interval (ULCI) = 0.082, tiredness/ fatigue: B = 0.050, LLCI = 0.040, ULCI = 0.060). This study demonstrates that stressful experiences impact the physical and mental health of people with endometriosis. The findings highlight the need to consider psychological approaches in the holistic management of people with endometriosis.

We report a case series of 2 patients with screw/shell interface failure in the Stryker Trident II Acetabular System. Both failures consisted of screw penetration through the Trident II acetabular shell. One failure was observed postoperatively after a revision from a cephalomedullary nail to a total hip arthroplasty while the other was observed intraoperatively during a primary total hip arthroplasty. Both component failures were managed conservatively with weight-bearing as tolerated and radiographic monitoring. These are the first reported cup/screw failures of the Stryker Trident II system and should raise awareness of the potential complication and implant design flaw. When placing acetabular screws, we recommend obtaining intraoperative orthogonal screw radiographs that are tangential to the shell surface to assess for screw/shell failure.

This method paper presents a template solution for text mining of scientific literature using the R tm package. Literature to be analyzed can be collected manually or automatically using the code provided with this paper. Once the literature is collected, the three steps for conducting text mining can be performed as outlined below: • loading and cleaning of text from articles, • processing, statistical analysis, and clustering, and • presentation of results using generalized and tailor-made visualizations.The text mining steps can be applied to a single, multiple, or time series groups of documents.References are provided to three published peer reviewed articles that use the presented text mining methodology. The main advantages of our method are: (1) Its suitability for both research and educational purposes, (2) Compliance with the Findable Accessible Interoperable and Reproducible (FAIR) principles, and (3) Code and example data are made available on GitHub under the open-source Apache V2 license.

The biology of bone healing is a rapidly developing science. Advances in transgenic and gene-targeted mice have enabled tissue and cell-specific investigations of skeletal regeneration. As an example, only recently has it been recognized that chondrocytes convert to osteoblasts during healing bone, and only several years prior, seminal publications reported definitively that the primary tissues contributing bone forming cells during regeneration were the periosteum and endosteum. While genetically modified animals offer incredible insights into the temporal and spatial importance of various gene products, the complexity and rapidity of healing-coupled with the heterogeneity of animal models-renders studies of regenerative biology challenging. Herein, cells that play a key role in bone healing will be reviewed and extracellular mediators regulating their behavior discussed. We will focus on recent studies that explore novel roles of inflammation in bone healing, and the origins and fates of various cells in the fracture environment. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Objective Several artificial intelligence (AI) systems for diabetic retinopathy screening have been validated but there is limited evidence on their performance in real-world settings. This study aimed to assess the performance of an AI software deployed within the diabetic retinopathy screening programme in Dominica.Methods and analysis We conducted a prospective, cross-sectional clinical validation study. Patients with diabetes aged 18 years and above attending the diabetic retinopathy screening in primary care facilities in Dominica from 5 June to 3 July 2021 were enrolled.Grading was done at the point of care by the field grader, followed by counselling and referral to the eye clinic. Images were then graded by an AI system. Sensitivity, specificity with 95% CIs and area under the curve (AUC) were calculated for comparing the AI to field grader as gold standard.Results A total of 587 participants were screened. The AI had a sensitivity and specificity for detecting referable diabetic retinopathy of 77.5% and 91.5% compared with the grader, for all participants, including ungradable images. The AUC was 0.8455. Excluding 52 participants deemed ungradable by the grader, the AI had a sensitivity and specificity of 81.4% and 91.5%, with an AUC of 0.9648.Conclusion This study provides evidence that AI has the potential to be deployed to assist a diabetic screening programme in a middle-income real-world setting and perform with reasonable accuracy compared with a specialist grader.