Conduction System Pacing Associated with Reduced Heart-Failure Hospitalizations and All-Cause Mortality Compared to Traditional Right Ventricular Pacing in the Medicare Population.

BACKGROUND: Conduction system pacing (CSP) has emerged as an alternative therapy to traditional right ventricular (RV) pacing. However, the majority of CSP studies reflect small cohorts or single-center experience. OBJECTIVE: This analysis compared CSP to dual-chamber (DC) RV pacing in a large, population-based cohort utilizing data from the Micra Coverage with Evidence Development (CED) study. METHODS: Medicare administrative claims data were used to identify patients implanted with a DC RV pacemaker. Lead placement data from Medtronic's device registration system identified patients treated with CSP (N=6,197) using a 3830 catheter-delivered lead or DC RV (non-3830 lead, non-CSP placement) (N=16,989) at the same centers. CSP patients were stratified into left bundle branch area pacing (LBBAP) (N=4,738) and His-bundle pacing (HBP) (N=1,459). Incident heart failure hospitalizations (iHFH), all-cause mortality, complication rates and reinterventions at 6 months were analyzed. RESULTS: CSP patients with a 3830 catheter-delivered lead experienced significantly lower rates of iHFH (HR: 0.70, P=0.02) and all-cause mortality at 6 months compared with DC RV patients (HR: 0.66, P<.0001). There was no difference in chronic complications (HR: 0.97, P=0.62) or need for reintervention (HR: 0.95, P=0.63) with CSP compared to DC RV, though LBBAP patients experienced significantly lower rates of complications (HR: 0.71, P=0.001) compared to HBP. CONCLUSION: Dual-chamber pacemaker patients treated with CSP using a 3830 catheter-delivered lead experienced significant all-cause mortality and HFH benefits compared to DC RV pacing. LBBAP had lower complications compared to HBP. These real-world results align with findings in small clinical studies demonstrating the benefits of CSP.

51Cr Red Blood Cells in the Study of Hematologic Disease: A Historical Review.

The early years of nuclear medicine included the development and clinical use of several in vitro or nonimaging procedures. The use of radionuclides as replacements for nonradioactive dyes brought improved accuracies and less subjective measurements to indicator dilution studies of body compartments such as the gastrointestinal system, lungs, urinary system, and vascular space. A popular nuclear medicine procedure was the radionuclide dilution method for quantitation of whole-blood volume or red blood cell volume or mass using 51Cr-labeled red blood cells-an important diagnostic element in patients suspected of having polycythemia vera, congestive heart failure, hypertension, shock, syncope, and other abnormal blood volume disorders. The radionuclide dilution method led to improved evaluation of red blood cell survival, which is important for clinical treatment planning in anemia and confirmation of splenic sequestration of damaged red blood cells. Although it was discovered that 51Cr was a chemically stable radiolabel of red blood cells after binding to intracellular hemoglobin, few nuclear medicine departments offered the clinical study for referring physicians because it required laboratory expertise for technologists, patient coordination, and a time-consuming procedure. The introduction of improved methods that are less time-consuming and have clinically acceptable results, along with the discontinuation of the sodium chromate 51Cr injection radiopharmaceutical by manufacturers, has consigned 51Cr red blood cells for red blood cell volume, mass, or survival evaluation to the list of retired nuclear medicine studies.

m6A modification plays an integral role in mRNA stability and translation during pattern-triggered immunity.

Plants employ distinct mechanisms to respond to environmental changes. Modification of mRNA by N 6-methyladenosine (m6A), known to affect the fate of mRNA, may be one such mechanism to reprogram mRNA processing and translatability upon stress. However, it is difficult to distinguish a direct role from a pleiotropic effect for this modification due to its prevalence in RNA. Through characterization of the transient knockdown-mutants of m6A writer components and mutants of specific m6A readers, we demonstrate the essential role that m6A plays in basal resistance and pattern-triggered immunity (PTI). A global m6A profiling of mock and PTI-induced Arabidopsis plants as well as formaldehyde fixation and cross-linking immunoprecipitation-sequencing of the m6A reader, EVOLUTIONARILY CONSERVED C-TERMINAL REGION2 (ECT2) showed that while dynamic changes in m6A modification and binding by ECT2 were detected upon PTI induction, most of the m6A sites and their association with ECT2 remained static. Interestingly, RNA degradation assay identified a dual role of m6A in stabilizing the overall transcriptome while facilitating rapid turnover of immune-induced mRNAs during PTI. Moreover, polysome profiling showed that m6A enhances immune-associated translation by binding to the ECT2/3/4 readers. We propose that m6A plays a positive role in plant immunity by destabilizing defense mRNAs while enhancing their translation efficiency to create a transient surge in the production of defense proteins.

Heterogeneous orientation tuning in the primary visual cortex of mice diverges from Gabor-like receptive fields in primates.

A key feature of neurons in the primary visual cortex (V1) of primates is their orientation selectivity. Recent studies using deep neural network models showed that the most exciting input (MEI) for mouse V1 neurons exhibit complex spatial structures that predict non-uniform orientation selectivity across the receptive field (RF), in contrast to the classical Gabor filter model. Using local patches of drifting gratings, we identified heterogeneous orientation tuning in mouse V1 that varied up to 90° across sub-regions of the RF. This heterogeneity correlated with deviations from optimal Gabor filters and was consistent across cortical layers and recording modalities (calcium vs. spikes). In contrast, model-synthesized MEIs for macaque V1 neurons were predominantly Gabor like, consistent with previous studies. These findings suggest that complex spatial feature selectivity emerges earlier in the visual pathway in mice than in primates. This may provide a faster, though less general, method of extracting task-relevant information.

Fast and accurate nonadiabatic molecular dynamics enabled through variational interpolation of correlated electron wavefunctions.

We build on the concept of eigenvector continuation to develop an efficient multi-state method for the rigorous and smooth interpolation of a small training set of many-body wavefunctions through chemical space at mean-field cost. The inferred states are represented as variationally optimal linear combinations of the training states transferred between the many-body bases of different nuclear geometries. We show that analytic multi-state forces and nonadiabatic couplings from the model enable application to nonadiabatic molecular dynamics, developing an active learning scheme to ensure a compact and systematically improvable training set. This culminates in application to the nonadiabatic molecular dynamics of a photoexcited 28-atom hydrogen chain, with surprising complexity in the resulting nuclear motion. With just 22 DMRG calculations of training states from the low-energy correlated electronic structure at different geometries, we infer the multi-state energies, forces and nonadiabatic coupling vectors at 12 000 geometries with provable convergence to high accuracy along an ensemble of molecular trajectories, which would not be feasible with a brute force approach. This opens up a route to bridge the timescales between accurate single-point correlated electronic structure methods and timescales of relevance for photo-induced molecular dynamics.

Incidence and economics of transvenous ICD lead complications: Implications for tricuspid valve function and interventions.

BACKGROUND: Implantable cardioverter-defibrillators are used globally and are reliable, but complications related to transvenous leads remain a concern. Evidence related to the incidence and costs of those complications is heterogeneous with respect to scope and healthcare system. This analysis aims to create estimates of the incidence and costs of tricuspid valve (TV) complications, lead failures, and lead extractions from a single large real-world data set. METHODS AND RESULTS: This retrospective longitudinal cohort study used the deidentified Medicare Fee for Service administrative claims database. A total of 116 036 patients with de novo transvenous ICD implant were analyzed. Mean hospital costs were $26 903 for tricuspid valve complications, $20 851 for lead failures, and $22 278 for lead extractions. CONCLUSIONS: Transvenous ICD lead complications incur significant costs to patients, hospitals, and payers when they occur. Advancements in lead technology that reduce these complications could bring significant clinical and economic value.

Energetics and Basic Stroke Kinematics of Swimming With Different Styles of Wetsuits.

ABSTRACT: Lim, B, Villalobos, A, Mercer, JA, and Crocker, GH. Energetics and basic stroke kinematics of swimming with different styles of wetsuits. J Strength Cond Res XX(X): 000-000, 2024-This study investigated the physiological responses and basic stroke kinematics while wearing different styles of wetsuits during submaximal intensity front-crawl swimming. Fourteen subjects (6 men and 8 women) completed a swimming-graded exercise test to determine maximal aerobic capacity (V̇O2max) and four 4-minute submaximal front-crawl swims at a pace that elicited 80% of V̇O2max with different wetsuits: regular swimsuit (no wetsuit [NWS]), buoyancy shorts (BS), sleeveless wetsuit (SLW), and full-sleeve wetsuit (FSW). The rate of oxygen consumption (V̇O2), rate of carbon dioxide production (V̇CO2), minute ventilation (V̇E), heart rate (HR), respiratory exchange ratio, and cost of swimming (CS) were determined as the average for the last minute of each trial. The rating of perceived exertion was assessed after each swimming bout. In addition, stroke length and index were determined from swimming pace and stroke rate. V̇O2, V̇CO2, V̇E, HR, and CS differed significantly among wetsuit conditions (p < 0.01). Respiratory exchange ratio and rating of perceived exertion also varied by wetsuit conditions (p < 0.05). However, stroke rate, length, and index were not significantly different across wetsuit conditions (p > 0.05). No differences existed between SLW and FSW for any dependent variable (p > 0.05). Results from this study suggest that swimming at the same pace without a wetsuit is the least economical, and both SLW and FSW are most and equally economical without significant kinematic changes. In addition, BS could be beneficial during training and racing in terms of less physiological demands than a regular swimsuit but not as economical as the SLW or FSW.

Using Large-Scale Sensor Data to Test Factors Predictive of Perseverance in Home Movement Rehabilitation: Early exercise frequency and schedule consistency.

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.

A framework for assessment of adverse events occurring in psychedelic-assisted therapies.

OBJECTIVE: Despite considerable research examining the efficacy of psychedelic-assisted therapies (PATs) for treating psychiatric disorders, assessment of adverse events (AEs) in PAT research has lagged. Current AE reporting standards in PAT trials are poorly calibrated to features of PAT that distinguish it from other treatments, leaving many potential AEs unassessed. METHODS: A multidisciplinary working group of experts involved in PAT pooled formally and informally documented AEs observed through research experience and published literature. This information was integrated with (a) current standards and practices for AE reporting in pharmacotherapy and psychotherapy trials and (b) published findings documenting post-acute dosing impacts of psychedelics on subjective states, meaning, and psychosocial health variables, to produce a set of AE constructs important to evaluate in PAT as well as recommended methods and time frames for their assessment and monitoring. Correspondence between identified potential AEs and current standards for AE assessment was examined, including the extent of coverage of identified AE constructs by 25 existing measures used in relevant research. RESULTS: Fifty-four potential AE terms warranting systematized assessment in PAT were identified, defined, and categorized. Existing measures demonstrated substantial gaps in their coverage of identified AE constructs. Recommendations were developed for how to assess PAT AEs (including patient, clinician, and informant reports), and when to assess over preparation, dosing session, integration, and follow-up. Application of this framework is demonstrated in a preliminary assessment protocol (available in the supplement). CONCLUSIONS: This assessment framework addresses the need to capture post-acute dosing AEs in PAT, accounting for its pharmacotherapy and psychotherapy components, as well as documented impacts of psychedelics on worldviews and spirituality.

Periprocedural Management and Multidisciplinary Care Pathways for Patients With Cardiac Implantable Electronic Devices: A Scientific Statement From the American Heart Association.

The rapid technological advancements in cardiac implantable electronic devices such as pacemakers, implantable cardioverter defibrillators, and loop recorders, coupled with a rise in the number of patients with these devices, necessitate an updated clinical framework for periprocedural management. The introduction of leadless pacemakers, subcutaneous and extravascular defibrillators, and novel device communication protocols underscores the imperative for clinical updates. This scientific statement provides an inclusive framework for the periprocedural management of patients with these devices, encompassing the planning phase, procedure, and subsequent care coordinated with the primary device managing clinic. Expert contributions from anesthesiologists, cardiac electrophysiologists, and cardiac nurses are consolidated to appraise current evidence, offer patient and health system management strategies, and highlight key areas for future research. The statement, pertinent to a wide range of health care professionals, underscores the importance of quality care pathways for patient safety, optimal device function, and minimization of hemodynamic disturbances or arrhythmias during procedures. Our primary objective is to deliver quality care to the expanding patient cohort with cardiac implanted electronic devices, offering direction in the era of evolving technologies and laying a foundation for sustained education and practice enhancement.

The Nested States Model: A Phenomenologically-Grounded Model of the Mind.

BACKGROUND: Subjective experience is central to the nature of mental illness, yet it has not played a central role in most empirical approaches to psychopathology. While phenomenological perspectives in psychiatry have seen a recent resurgence, there remains a need for more detailed models of psychopathological processes based on explicit phenomenological and enactive foundations. SUMMARY: We present a framework derived from the Nested States Model (NSM) through which such phenomenologically-grounded models might be constructed. The NSM describes the dynamic structure of subjective experience as a system of nested states that reciprocally influence one another across hierarchical layers. Here, we show how the NSM provides a scheme for characterizing patterns of experience that comprise various psychopathological processes. We demonstrate the utility of this scheme both for clinical practice and for building our knowledge of psychopathological processes more broadly. KEY MESSAGES: The NSM can advance three aims that we see as critical for the lasting integration of phenomenological approaches to psychopathology within psychiatry. First, we show that the NSM provides a means for constructing clinical formulations and treatment considerations that center squarely on an individual's subjective experiences. Second, the NSM supplies a framework for organizing findings from clinical-phenomenological research that can guide the construction of broader phenomenologically-grounded models of psychopathological processes. Lastly, the NSM aligns our perspective on subjective experience with emerging perspectives on brain dynamics, helping to bridge phenomenological work with ongoing neurophysiological research.

Hospital Chaplain Burnout, Depression, and Well-Being during the COVID-19 Pandemic.

Healthcare personnel experienced unprecedented stressors and risk factors for burnout, anxiety, and depression during the COVID-19 pandemic. This may have been particularly true for spiritual health clinicians (SHCs), also referred to as healthcare chaplains. We administered a daily pulse survey that allowed SHCs to self-report burnout, depression, and well-being, administered every weekday for the first year of the pandemic. We used a series of linear regression models to evaluate whether burnout, depression, and well-being were associated with local COVID-19 rates in the chaplains' hospital system (COVID-19 admissions, hospital deaths from COVID-19, and COVID-19 ICU census). We also compared SHC weekly rates with national averages acquired by the U.S. Census Bureau's Household Pulse Survey (HPS) data during the same timeframe. Of the 840 daily entries from 32 SHCs, 90.0% indicated no symptoms of burnout and 97.1% were below the cutoff for depression. There was no statistically significant relationship between any of the COVID-19 predictors and burnout, depression, or well-being. Mean national PHQ-2 scores were consistently higher than our sample's biweekly means. Understanding why SHCs were largely protected against burnout and depression may help in addressing the epidemic of burnout among healthcare providers and for preparedness for future healthcare crises.

HemN2 Regulates the Virulence of Pseudomonas donghuensis HYS through 7-Hydroxytropolone Synthesis and Oxidative Stress.

Compared to pathogens Pseudomonas aeruginosa and P. putida, P. donghuensis HYS has stronger virulence towards Caenorhabditis elegans. However, the underlying mechanisms haven't been fully understood. The heme synthesis system is essential for Pseudomonas virulence, and former studies of HemN have focused on the synthesis of heme, while the relationship between HemN and Pseudomonas virulence were barely pursued. In this study, we hypothesized that hemN2 deficiency affected 7-hydroxytropolone (7-HT) biosynthesis and redox levels, thereby reducing bacterial virulence. There are four hemN genes in P. donghuensis HYS, and we reported for the first time that deletion of hemN2 significantly reduced the virulence of HYS towards C. elegans, whereas the reduction in virulence by the other three genes was not significant. Interestingly, hemN2 deletion significantly reduced colonization of P. donghuensis HYS in the gut of C. elegans. Further studies showed that HemN2 was regulated by GacS and participated in the virulence of P. donghuensis HYS towards C. elegans by mediating the synthesis of the virulence factor 7-HT. In addition, HemN2 and GacS regulated the virulence of P. donghuensis HYS by affecting antioxidant capacity and nitrative stress. In short, the findings that HemN2 was regulated by the Gac system and that it was involved in bacterial virulence via regulating 7-HT synthesis and redox levels were reported for the first time. These insights may enlighten further understanding of HemN-based virulence in the genus Pseudomonas.

Left Atrial Appendage Closure: Therapy Overview and Future Perspective.

The left atrial appendage (LAA) has gained increasing attention in the field of cardiology as a potential site for intervention in patients with atrial fibrillation (AF) and an elevated risk of thromboembolic events. Left atrial appendage occlusion (LAAO) has emerged as a promising therapeutic strategy to mitigate the risk of stroke and systemic embolism, especially in individuals who are unsuitable candidates for long-term anticoagulation therapy. This review aims to provide a comprehensive analysis of the current state of LAAO, encompassing its anatomic considerations, procedural techniques, clinical outcomes, and future directions.

Neural topic models with survival supervision: Jointly predicting time-to-event outcomes and learning how clinical features relate.

We present a neural network framework for learning a survival model to predict a time-to-event outcome while simultaneously learning a topic model that reveals feature relationships. In particular, we model each subject as a distribution over "topics", where a topic could, for instance, correspond to an age group, a disorder, or a disease. The presence of a topic in a subject means that specific clinical features are more likely to appear for the subject. Topics encode information about related features and are learned in a supervised manner to predict a time-to-event outcome. Our framework supports combining many different topic and survival models; training the resulting joint survival-topic model readily scales to large datasets using standard neural net optimizers with minibatch gradient descent. For example, a special case is to combine LDA with a Cox model, in which case a subject's distribution over topics serves as the input feature vector to the Cox model. We explain how to address practical implementation issues that arise when applying these neural survival-supervised topic models to clinical data, including how to visualize results to assist clinical interpretation. We study the effectiveness of our proposed framework on seven clinical datasets on predicting time until death as well as hospital ICU length of stay, where we find that neural survival-supervised topic models achieve competitive accuracy with existing approaches while yielding interpretable clinical topics that explain feature relationships. Our code is available at: https://github.com/georgehc/survival-topics.

Genotypes and phenotypes of motor neuron disease: an update of the genetic landscape in Scotland.

BACKGROUND: Using the Clinical Audit Research and Evaluation of Motor Neuron Disease (CARE-MND) database and the Scottish Regenerative Neurology Tissue Bank, we aimed to outline the genetic epidemiology and phenotypes of an incident cohort of people with MND (pwMND) to gain a realistic impression of the genetic landscape and genotype-phenotype associations. METHODS: Phenotypic markers were identified from the CARE-MND platform. Sequence analysis of 48 genes was undertaken. Variants were classified using a structured evidence-based approach. Samples were also tested for C9orf72 hexanucleotide expansions using repeat-prime PCR methodology. RESULTS: 339 pwMND donated a DNA sample: 44 (13.0%) fulfilled criteria for having a pathogenic variant/repeat expansion, 53.5% of those with a family history of MND and 9.3% of those without. The majority (30 (8.8%)) had a pathogenic C9orf72 repeat expansion, including two with intermediate expansions. Having a C9orf72 expansion was associated with a significantly lower Edinburgh Cognitive and Behavioural ALS Screen ALS-Specific score (p = 0.0005). The known pathogenic SOD1 variant p.(Ile114Thr), frequently observed in the Scottish population, was detected in 9 (2.7%) of total cases but in 17.9% of familial cases. Rare variants were detected in FUS and NEK1. One individual carried both a C9orf72 expansion and SOD1 variant. CONCLUSIONS: Our results provide an accurate summary of MND demographics and genetic epidemiology. We recommend early genetic testing of people with cognitive impairment to ensure that C9orf72 carriers are given the best opportunity for informed treatment planning. Scotland is enriched for the SOD1 p.(Ile114Thr) variant and this has significant implications with regards to future genetically-targeted treatments.

How will early onset scoliosis surgery affect my child's future as a young adult? A follow-up study using patient-reported outcome measures.

PURPOSE: Using patient-reported outcome measures (PROMs), this study was undertaken to determine how well patients with early onset scoliosis (EOS) fare in adulthood. METHODS: Among eight healthcare centers, 272 patients (≥ 18 years) surgically managed for EOS (≥ 5 years) completed the Scoliosis Research Society (SRS)-22r, Functional Assessment of Chronic Illness Therapy-10 (FACIT-Dyspnea-10), and Short Form (SF)-12. Functional and demographic data were collected. RESULTS: The response rate was 40% (108/272). EOS etiologies were congenital (45%), neuromuscular (20%), idiopathic (20%) syndromic (11%), and unknown (4%). All patients scored within normal limits on the FACIT-Dyspnea-10 pulmonary (no breathing aids, 78%; no oxygen, 92%). SF-12 physical health scores and most SRS-22r domains were significantly decreased (p < 0.05 and p < 0.001, respectively) compared with normative values. SF-12 and SRS-22r mental health scores (MHS) were lower than normative values (p < 0.05 and p < 0.02, respectively). Physical health PROMs varied between etiologies. Treatment varied by etiology. Patients with congenital EOS were half as likely to undergo definitive fusion. There was no difference between EOS etiologies in SF-12 MHS, with t scores being slightly lower than normative peers. CONCLUSION: Good long-term physical and social function and patient-reported quality of life were noted in surgically managed patients. Patients with idiopathic EOS physically outperformed those with other etiologies in objective and PROM categories but had similar MHS PROMs. Compared to normative values, EOS patients demonstrated decreased long-term physical capacity, slightly lower MHS, and preserved cardiopulmonary function. LEVEL OF EVIDENCE: Level IV Case Series.

Global LEADR pivotal trial results.

BACKGROUND: Implantable cardioverter-defibrillators last longer, and interest in reliable leads with targeted lead placement is growing. The OmniaSecure™ defibrillation lead is a novel small-diameter, catheter-delivered lead designed for targeted placement, based on the established SelectSecure SureScan MRI Model 3830 lumenless pacing lead platform. OBJECTIVE: This trial assessed safety and efficacy of the OmniaSecure defibrillation lead. METHODS: The worldwide LEADR pivotal clinical trial enrolled patients indicated for de novo implantation of a primary or secondary prevention implantable cardioverter-defibrillator/cardiac resynchronization therapy defibrillator, all of whom received the study lead. The primary efficacy end point was successful defibrillation at implantation per protocol. The primary safety end point was freedom from study lead-related major complications at 6 months. The primary efficacy and safety objectives were met if the lower bound of the 2-sided 95% credible interval was >88% and >90%, respectively. RESULTS: In total, 643 patients successfully received the study lead, and 505 patients have completed 12-month follow-up. The lead was placed in the desired right ventricular location in 99.5% of patients. Defibrillation testing at implantation was completed in 119 patients, with success in 97.5%. The Kaplan-Meier estimated freedom from study lead-related major complications was 97.1% at 6 and 12 months. The trial exceeded the primary efficacy and safety objective thresholds. There were zero study lead fractures and electrical performance was stable throughout the mean follow-up of 12.7 ± 4.8 months (mean ± SD). CONCLUSION: The OmniaSecure lead exceeded prespecified primary end point performance goals for safety and efficacy, demonstrating high defibrillation success and a low occurrence of lead-related major complications with zero lead fractures.

Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND): a multicentre, parallel, randomised controlled trial in the UK.

BACKGROUND: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease. METHODS: We conducted a parallel, multicentre, two-arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web-based system, stratified by site. Participants were followed up at 6 months and 9 months post-randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire-Revised (MQOL-R) at 6 months post-randomisation. Primary analyses were multi-level modelling and modified intention to treat among participants with available data. This trial was pre-registered with the ISRCTN Registry (ISRCTN12655391). FINDINGS: Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63·1 years (SD 11·0). 155 (81%) participants had primary outcome data at 6 months post-randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0·66 [95% CI 0·22-1·10]; d=0·46 [0·16-0·77]; p=0·0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention. INTERPRETATION: ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services. FUNDING: National Institute for Health and Care Research Health Technology Assessment and Motor Neurone Disease Association.

Outcomes after completing growth-friendly surgical treatment for early-onset scoliosis in patients with skeletal dysplasia.

Aims: The aim of this study was to compare outcomes after growth-friendly treatment for early-onset scoliosis (EOS) between patients with skeletal dysplasias versus those with other syndromes. Methods: We retrospectively identified 20 patients with skeletal dysplasias and 292 with other syndromes (control group) who had completed surgical growth-friendly EOS treatment between 1 January 2000 and 31 December 2018. We compared radiological parameters, complications, and health-related quality of life (HRQoL) at mean follow-up of 8.6 years (SD 3.3) in the dysplasia group and 6.6 years (SD 2.6) in the control group. Results: Mean major curve correction per patient did not differ significantly between the dysplasia group (43%) and the control group (28%; p = 0.087). Mean annual spinal height increase was less in the dysplasia group (9.3 mm (SD 5.1) than in the control group (16 mm (SD 9.2); p < 0.001). Mean annual spinal growth adjusted to patient preoperative standing height during the distraction period was 11% in the dysplasia group and 14% in the control group (p = 0.070). The complication rate was 1.6 times higher (95% confidence interval (CI) 1.3 to 2.0) in the dysplasia group. The following complications were more frequent in the dysplasia group: neurological injury (rate ratio (RR) 5.1 (95% CI 2.3 to 11)), deep surgical site infection (RR 2.2 (95% CI 1.2 to 4.1)), implant-related complications (RR 2.0 (95% CI 1.5 to 2.7)), and unplanned revision (RR 1.8 (95% CI 1.3 to 2.5)). Final fusion did not provide additional spinal height compared with watchful waiting (p = 0.054). There were no significant differences in HRQoL scores between the groups. Conclusion: After growth-friendly EOS treatment, patients with skeletal dysplasias experienced a higher incidence of complications compared to those with other syndromes. Surgical growth-friendly treatment for skeletal dysplasia-associated EOS should be reserved for patients with severe, progressive deformities that are refractory to nonoperative treatment.