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Abstract Background Guidelines promote shared decision-making (SDM) for anticoagulation in patients with atrial fibrillation (AF). We recently showed that adding a within-encounter SDM tool to usual care (UC) increases patient involvement in decision making and clinician satisfaction, without affecting encounter length. Purpose We aimed to estimate the extent to which use of an SDM tool affected patient adherence to the decided care plan and clinical safety endpoints. Methods We conducted a multi-center, encounter-level randomized trial assessing the efficacy of UC with vs. without an SDM conversation tool for use during the clinical encounter (Anticoagulation Choice, AC) in patients with non-valvular AF considering starting or reviewing anticoagulation treatment. We conducted a chart and pharmacy review, blinded to randomization status, at 10 months post-enrollment to assess primary adherence (proportion of patients who were prescribed an anticoagulant who filled their first prescription) and secondary adherence (estimated using the proportion of days for which treatment was supplied and filled [PDC] for DOAC, and as time in therapeutic range (TTR) for warfarin). We also followed for any safety outcomes (stroke [stroke or transient ischemic attack], major bleeding, or death). Results We enrolled 922 evaluable patient encounters (AC=463, UC=459), of which 814 (88%) had pharmacy and clinical follow-up. We found no differences between arms in either primary (78% of patients in AC filled their first prescription vs. 81% in UC) or secondary adherence to anticoagulation (see Figure, PDCDOAC was 74.1% in AC vs. 71.6% in UC; TTRwarfarin was 66.6% in AC vs. 64.4% in UC). PDCDOAC was better (65%) in AC than in UC (55%) (OR 1.49, CIs 1.00, 2.22). Safety outcomes, mostly bleeds, occurred in 13% (AC) of and 14% (UC) of participants. Conclusions This is the largest reported randomized trial in AF comparing usual care with and without an SDM tool to promote SDM. Although patients were more actively involved in SDM, we found no significant differences between arms in primary or secondary adherence to anticoagulation or clinical safety outcomes. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): The trial was funded by and conducted independently of the National Heart, Lung, and Blood Institute (NHLBI) of the U.S. National Institutes of Health (RO1 HL131535-01). The funding body had no influence on the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Figure 1

Background Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results ICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

Background: Patient-reported outcomes (PROs) measure progression and quality of care. While legacy PROs such as the International Knee Documentation Committee (IKDC) survey are well-validated, a lengthy PRO creates a time burden on patients, decreasing adherence. In recent years, PROs such as the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function and Pain Interference surveys were developed as computer adaptive tests, reducing time to completion. Previous studies have examined correlation between legacy PROs and PROMIS; however, no studies have developed effective prediction models utilizing PROMIS to create an IKDC index. While the IKDC is the standard knee PRO, computer adaptive PROs offer numerous practical advantages. Purpose: To develop a nonlinear predictive model utilizing PROMIS Physical Function and Pain Interference to estimate IKDC survey scores and examine algorithm sensitivity and validity. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: The MOTION (Military Orthopaedics Tracking Injuries and Outcomes Network) database is a prospectively collected repository of PROs and intraoperative variables. Patients undergoing knee surgery completed the IKDC and PROMIS surveys at varying time points. Nonlinear multivariable predictive models using Gaussian and beta distributions were created to establish an IKDC index score, which was then validated using leave-one-out techniques and minimal clinically important difference analysis. Results: A total of 1011 patients completed the IKDC and PROMIS Physical Function and Pain Interference, providing 1618 complete observations. The algorithms for the Gaussian and beta distribution were validated to predict the IKDC (Pearson = 0.84-0.86; R 2 = 0.71-0.74; root mean square error = 9.3-10.0). Conclusion: The publicly available predictive models can approximate the IKDC score. The results can be used to compare PROMIS Physical Function and Pain Interference against historical IKDC scores by creating an IKDC index score. Serial use of the IKDC index allows for a lower minimal clinically important difference than the conventional IKDC. PROMIS can be substituted to reduce patient burden, increase completion rates, and produce orthopaedic-specific survey analogs.

Abstract Context Familial partial lipodystrophy (FPL), Dunnigan variety is characterized by skeletal muscle hypertrophy and insulin resistance besides fat loss from the extremities. The cause for the muscle hypertrophy and its functional consequences is not known. Objective To compare muscle strength and endurance, besides muscle protein synthesis rate between subjects with FPL and matched controls (n = 6 in each group). In addition, we studied skeletal muscle mitochondrial function and gene expression pattern to help understand the mechanisms for the observed differences. Methods Body composition by dual-energy X-ray absorptiometry, insulin sensitivity by minimal modelling, assessment of peak muscle strength and fatigue, skeletal muscle biopsy and calculation of muscle protein synthesis rate, mitochondrial respirometry, skeletal muscle transcriptome, proteome, and gene set enrichment analysis. Results Despite increased muscularity, FPL subjects did not demonstrate increased muscle strength but had earlier fatigue on chest press exercise. Decreased mitochondrial state 3 respiration in the presence of fatty acid substrate was noted, concurrent to elevated muscle lactate and decreased long-chain acylcarnitine. Based on gene transcriptome, there was significant downregulation of many critical metabolic pathways involved in mitochondrial biogenesis and function. Moreover, the overall pattern of gene expression was indicative of accelerated aging in FPL subjects. A lower muscle protein synthesis and downregulation of gene transcripts involved in muscle protein catabolism was observed. Conclusion Increased muscularity in FPL is not due to increased muscle protein synthesis and is likely due to reduced muscle protein degradation. Impaired mitochondrial function and altered gene expression likely explain the metabolic abnormalities and skeletal muscle dysfunction in FPL subjects.

Abstract At present, no research criteria exist for the diagnosis of prodromal behavioural variant frontotemporal dementia (bvFTD), though early detection is of high research importance. Thus, we sought to develop and validate a proposed set of research criteria for prodromal bvFTD, termed ‘mild behavioural and/or cognitive impairment in bvFTD’ (MBCI-FTD). Participants included 72 participants deemed to have prodromal bvFTD; this comprised 55 carriers of a pathogenic mutation known to cause frontotemporal lobar degeneration, and 17 individuals with autopsy-confirmed frontotemporal lobar degeneration. All had mild behavioural and/or cognitive changes, as judged by an evaluating clinician. Based on extensive clinical workup, the prodromal bvFTD group was divided into a Development Group (n = 22) and a Validation Group (n = 50). The Development Group was selected to be the subset of the prodromal bvFTD group for whom we had the strongest longitudinal evidence of conversion to bvFTD, and was used to develop the MBCI-FTD criteria. The Validation Group was the remainder of the prodromal bvFTD group and was used as a separate sample on which to validate the criteria. Familial non-carriers were included as healthy controls (n = 165). The frequencies of behavioural and neuropsychiatric features, neuropsychological deficits, and social cognitive dysfunction in the prodromal bvFTD Development Group and healthy controls were assessed. Based on sensitivity and specificity analyses, seven core features were identified: apathy without moderate-severe dysphoria, behavioural disinhibition, irritability/agitation, reduced empathy/sympathy, repetitive behaviours (simple and/or complex), joviality/gregariousness, and appetite changes/hyperorality. Supportive features include a neuropsychological profile of impaired executive function or naming with intact orientation and visuospatial skills, reduced insight for cognitive or behavioural changes, and poor social cognition. Three core features or two core features plus one supportive feature are required for the diagnosis of possible MBCI-FTD; probable MBCI-FTD requires imaging or biomarker evidence, or a pathogenic genetic mutation. The proposed MBCI-FTD criteria correctly classified 95% of the prodromal bvFTD Development Group, and 74% of the prodromal bvFTD Validation Group, with a false positive rate of <10% in healthy controls. Finally, the MBCI-FTD criteria were tested on a cohort of individuals with prodromal Alzheimer’s disease, and the false positive rate of diagnosis was 11–16%. Future research will need to refine the sensitivity and specificity of these criteria, and incorporate emerging biomarker evidence.

AbstractObjectiveTo support patient‐centred care and the collaboration of patients and clinicians, we developed and pilot tested a conversation aid for patients with thyroid nodules.Design, Patient and MeasurementsWe developed a web‐based Thyroid NOdule Conversation aid (TNOC) following a human‐centred design. A proof of concept observational pre–post study was conducted (TNOC vs. usual care [UC]) to assess the impact of TNOC on the quality of conversations. Data sources included recordings of clinical visits, post‐encounter surveys and review of electronic health records. Summary statistics and group comparisons are reported.ResultsSixty‐five patients were analysed (32 in the UC and 33 in the TNOC cohort). Most patients were women (89%) with a median age of 57 years and were incidentally found to have a thyroid nodule (62%). Most thyroid nodules were at low risk for thyroid cancer (71%) and the median size was 1.4 cm. At baseline, the groups were similar except for higher numeracy in the TNOC cohort. The use of TNOC was associated with increased involvement of patients in the decision‐making process, clinician satisfaction and discussion of relevant topics for decision making. In addition, decreased decisional conflict and fewer thyroid biopsies as the next management step were noted in the TNOC cohort. No differences in terms of knowledge transfer, length of consultation, thyroid cancer risk perception or concern for thyroid cancer diagnosis were found.ConclusionIn this pilot observational study, using TNOC in clinical practice was feasible and seemed to help the collaboration of patients and clinicians.

Study Design This study is a retrospective case control. Objectives This study aims to determine whether cervical degenerative spondylolisthesis (DS) is associated with increased baseline neck/arm pain and inferior health quality states compared to a similar population without DS. Methods Patient demographics, pre-operative radiographs, and baseline PROMs were reviewed for 315 patients undergoing anterior cervical decompression and fusion (ACDF) with at least 1 year of follow-up. Patients were categorized based on the presence (S) or absence of a spondylolisthesis (NS). Statistically significant variables were further explored using multiple linear regression analysis. Results 49/242 (20%) patients were diagnosed with DS, most commonly at the C4–5 level (27/49). The S group was significantly older than the NS group (58.0 ± 10.7 vs 51.9 ± 9.81, P = .001), but otherwise, no demographic differences were identified. Although a higher degree of C2 slope was found among the S cohort (22.5 ± 8.63 vs 19.8 ± 7.78, P = .044), no differences were identified in terms of preoperative visual analogue scale (VAS) neck pain or NDI. In the univariate analysis, the NS group had significantly increased VAS arm pain relative to the S group (4.93 ± 3.16 vs 3.86 ± 3.30, P = .045), which was no longer significant in the multivariate analysis. Conclusions Although previous reports have suggested an association between cervical DS and neck pain, we could not associate the presence of DS with increased baseline neck or arm pain. Instead, DS appears to be a relatively frequent (20% in this series) age-related condition reflecting radiographic, rather than necessarily clinical, disease.