Structural insights into intron catalysis and dynamics during splicing.

The group II intron ribonucleoprotein is an archetypal splicing system with numerous mechanistic parallels to the spliceosome, including excision of lariat introns1,2. Despite the importance of branching in RNA metabolism, structural understanding of this process has remained elusive. Here we present a comprehensive analysis of three single-particle cryogenic electron microscopy structures captured along the splicing pathway. They reveal the network of molecular interactions that specifies the branchpoint adenosine and positions key functional groups to catalyse lariat formation and coordinate exon ligation. The structures also reveal conformational rearrangements of the branch helix and the mechanism of splice site exchange that facilitate the transition from branching to ligation. These findings shed light on the evolution of splicing and highlight the conservation of structural components, catalytic mechanism and dynamical strategies retained through time in premessenger RNA splicing machines.

Bicuspid valve CT registry of balloon-expandable TAVR: BETTER TAVR registry.

BACKGROUND: The anatomic substrate of bicuspid valves may lead to suboptimal TAVR stent expansion and geometry. AIM: We evaluated determinants of stent geometry in bicuspid valves treated with Sapien transcatheter aortic valve replacement (TAVR) valves. METHODS: A multicenter retrospective registry of patients (February 2019 to August 2022) who underwent post-TAVR computed tomography to determine stent area (vs. nominal valve area) and stent ellipticity (maximum diameter/minimum diameter). Predictors of relative stent expansion (minimum area/average of inflow + outflow area) and stent ellipticity were evaluated in a multivariable regression model, including valve calcium volume (indexed by annular area), presence of raphe calcium, sinus diameters indexed by area-derived annular diameter, and performance of pre-dilation and post-dilation. RESULTS: The registry enrolled 101 patients from four centers. The minimum stent area (vs. nominal area) was 88.1%, and the maximum ellipticity was 1.10, with both observed near the midframe of the valve in all cases. Relative stent expansion ≥90% was observed in 64/101 patients. The only significant predictor of relative stent expansion ≥90% was the performance of post-dilation (OR: 4.79, p = 0.018). Relative stent expansion ≥90% was seen in 86% of patients with post-dilation compared to 57% without (p < 0.001). The stent ellipticity ≥1.1 was observed in 47/101 patients. The significant predictors of stent ellipticity ≥1.1 were the indexed maximum sinus diameter (OR: 0.582, p = 0.021) and indexed intercommisural diameter at 4 mm (OR: 2.42, p = 0.001). Stent expansion has a weak negative correlation with post-TAVR mean gradient (r = -0.324, p < 0.001). CONCLUSION: Relative stent expansion ≥90% was associated with the performance of post-dilation, and stent ellipticity ≥1.1 was associated with indexed intercommisural diameter and indexed maximum sinus diameter. Further studies to determine optimal deployment strategies in bicuspid valves are needed.

Sepsis-associated acute kidney injury: recent advances in enrichment strategies, sub-phenotyping and clinical trials.

Acute kidney injury (AKI) often complicates sepsis and is associated with high morbidity and mortality. In recent years, several important clinical trials have improved our understanding of sepsis-associated AKI (SA-AKI) and impacted clinical care. Advances in sub-phenotyping of sepsis and AKI and clinical trial design offer unprecedented opportunities to fill gaps in knowledge and generate better evidence for improving the outcome of critically ill patients with SA-AKI. In this manuscript, we review the recent literature of clinical trials in sepsis with focus on studies that explore SA-AKI as a primary or secondary outcome. We discuss lessons learned and potential opportunities to improve the design of clinical trials and generate actionable evidence in future research. We specifically discuss the role of enrichment strategies to target populations that are most likely to derive benefit and the importance of patient-centered clinical trial endpoints and appropriate trial designs with the aim to provide guidance in designing future trials.

Shifting Mindsets: The Impact of a Patient Portal on Functioning and Recovery in a Mental Health Setting.

OBJECTIVE: This study aims to understand whether higher use of a patient portal can have an impact on mental health functioning and recovery. METHOD: A mixed methods approach was used for this study. In 2019-2021, patients with mental health diagnoses at outpatient clinics in an academic centre were invited to complete World Health Organization Disability Assessment Scale 12 (WHODAS-12) and Mental Health Recovery Measure surveys at baseline, 3 months, and 6 months after signing up for the portal. At the 3-month time point, patients were invited to a semistructured interview with a member of the team to contextualize the findings obtained from the surveys. Analytics data was also collected from the platform to understand usage patterns on the portal. RESULTS: Overall, 113 participants were included in the analysis. There was no significant change in mental health functioning and recovery scores over the 6-month period. However, suboptimal usage was observed as 46% of participants did not complete any tasks within the portal. Thirty-five participants had low use of the portal (1-9 interactions) and 18 participants had high usage (10+ interactions). There were also no differences in mental health functioning and recovery scores between low and high users of the portal. Qualitative interviews highlighted many opportunities where the portal can support overall functioning and mental health recovery. CONCLUSIONS: Collectively, this study suggests that higher use of a portal had no impact, either positive or negative, on mental health outcomes. While it may offer convenience and improved patient satisfaction, adequate support is needed to fully enable these opportunities for patient care. As the type of interaction with the portal was not specifically addressed, future work should focus on looking at ways to support patient engagement and portal usage throughout their care journey.

Intravenous Autologous Bone Marrow-derived Mesenchymal Stromal Cells Delay Acute Respiratory Distress Syndrome in Swine.

Rationale: Early post injury mitigation strategies in ARDS are in short supply. Treatments with allogeneic stromal cells are administered after ARDS develops, require specialized expertise and equipment, and to date have shown limited benefit. Objectives: Assess the efficacy of immediate post injury intravenous administration of autologous or allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) for the treatment of acute respiratory distress syndrome (ARDS) due to smoke inhalation and burns. Methods: Yorkshire swine (n = 32, 44.3 ± 0.5 kg) underwent intravenous anesthesia, placement of lines, severe smoke inhalation, and 40% total body surface area flame burns, followed by 72 hours of around-the-clock ICU care. Mechanical ventilation, fluids, pressors, bronchoscopic cast removal, daily lung computed tomography scans, and arterial blood assays were performed. After injury and 24 and 48 hours later, animals were randomized to receive autologous concentrated bone marrow aspirate (n = 10; 3 × 106 white blood cells and a mean of 56.6 × 106 platelets per dose), allogeneic MSCs (n = 10; 6.1 × 106 MSCs per dose) harvested from healthy donor swine, or no treatment in injured control animals (n = 12). Measurements and Main Results: The intravenous administration of MSCs after injury and at 24 and 48 hours delayed the onset of ARDS in swine treated with autologous MSCs (48 ± 10 h) versus control animals (14 ± 2 h) (P = 0.004), reduced ARDS severity at 24 (P < 0.001) and 48 (P = 0.003) hours, and demonstrated visibly diminished consolidation on computed tomography (not significant). Mortality at 72 hours was 1 in 10 (10%) in the autologous group, 5 in 10 (50%) in the allogeneic group, and 6 in 12 (50%) in injured control animals (not significant). Both autologous and allogeneic MSCs suppressed systemic concentrations of TNF-α (tumor necrosis factor-α). Conclusions: The intravenous administration of three doses of freshly processed autologous bone marrow-derived MSCs delays ARDS development and reduces its severity in swine. Bedside retrieval and administration of autologous MSCs in swine is feasible and may be a viable injury mitigation strategy for ARDS.

Employer-Sponsored Medicare Advantage Plans and the 2018 Therapy Cap Repeal: Reduced Overall Spending Does Not Constrain Out-of-Pocket Costs.

BACKGROUND: Policy impacting traditional Medicare beneficiaries may have unintended effects for privately insured patients. After the repeal of a longstanding $1500 outpatient therapy cap in 2018, we aimed to evaluate if this policy change was associated with differences in use of cost of postoperative therapy after common hand surgeries, including carpal tunnel release, trigger finger release, ganglion cyst excision, De Quervain tenosynovitis release, carpometacarpal arthroplasty, and distal radius fracture open reduction/internal fixation or percutaneous pinning. METHODS: The Medicare Supplement and Coordination of Benefits files from Marketscan were used. Frequency of therapy appointments, overall costs, and out-of-pocket costs were obtained. A segmented interrupted time series with Poisson and log-transformed linear regression was performed. RESULTS: No significant monthly change in odds of therapy use was found in the postpolicy period for patients who underwent trigger finger release, carpal tunnel release, Ganglion cyst excision, De Quervain tenosynovitis release, carpometacarpal arthroplasty, or distal radius fracture, pinning, or open reduction/internal fixation. Overall cost decreased in the postpolicy period by 2% for comprehensive plans (95% confidence interval [CI]: -0.03 to -0.01, P < 0.001), by 7% for those with exclusive provider organizations (95% CI: -0.10 to -0.04, P < 0.001), by 1% for HMOs (95% CI: -0.01 to 0.002, P = 0.01), and by 3% for preferred provider organizations (95% CI: -0.03 to -0.02, P < 0.001). In the postpolicy period, no monthly change in out-of-pocket cost was observed for patients with comprehensive, exclusive provider organization, health maintenance organization, preferred provider organization, or point of service with capitation insurance plans. CONCLUSIONS: Patients with employer-sponsored Medicare Advantage plans experienced increased out-of-pocket costs for therapy despite lower net costs. These data highlight an urgent need for policy ensuring that patients benefit when overall costs of care decrease.

Can a multicomponent positive psychological intervention promote well-being in parents of young children? A randomized controlled trial study in Hong Kong.

The present research examined the effects of an Early Advancement in Social-Emotional Health and Positivity (EASP) multicomponent positive psychological intervention on parents' well-being in Hong Kong. Participants were parents of young children (N = 120; Mage = 37.19 years, SD = 4.71, range = 24-53; female = 95.00%) who participated in the one-month randomized control trial. Participants were randomly assigned into the intervention (n = 50) and waitlist control groups (n = 70). Parents in the intervention group received two online workshops and an evidence-based smartphone application that targeted four positive psychological skills: (1) mindful parenting, (2) hope, (3) positive reappraisal, and (4) growth mindset. The results of the multivariate regression analysis revealed that the intervention significantly improved various dimensions of participants' positive psychological skills, subjective well-being, and psychological well-being immediately at the conclusion of the program. The findings of this study underscore the importance of the well-being payoffs linked to cultivating positive psychological skills among parents of young children.

The Impact of Timing of Delayed Autologous Breast Reconstruction following Postmastectomy Radiation Therapy on Postoperative Morbidity.

BACKGROUND: The ideal time to perform reconstruction after the completion of postmastectomy radiation therapy (PMRT) in patients with locally advanced breast cancer is currently unknown. We evaluate the association between the timing of delayed autologous breast reconstruction following PMRT and postoperative complications. METHODS: Patients who underwent mastectomy, PMRT, and then delayed autologous breast reconstruction from 2009 to 2016 were identified from the Truven Health MarketScan Research Databases. Timing of reconstruction following PMRT was grouped 0-3, 3-6, 6-12, 12-24, and after 24 months. Multivariable models were used to assess associations between timing of reconstruction following PMRT and key measures of morbidity. RESULTS: A total of 1,039 patients met inclusion criteria. The rate of any complications for the analytic cohort was 39.4%, including 13.3% of patients who experienced wound complications and 11.3% of patients requiring additional flaps. Unadjusted rates of complications increased from 23.4% between 0 and 3 months to 49.4% between 3 and 6 months and decreased thereafter. Need for additional flaps was highest within 3 to 6 months (14.0%). Multivariate analysis revealed higher rates of any complications when reconstruction was performed between 3 and 6 months (odds ratio [OR]: 3.04, p < 0.001), 6 and 12 months (OR: 2.66, p < 0.001), or 12 and 24 months (OR: 2.13, p = 0.001) after PMRT. No difference in complications were noted in reconstructions performed after 24 months compared with those performed before 3 months (p > 0.05). However, rates of wound complications were least likely in reconstructions after 24 months (OR: 0.34, p = 0.035). CONCLUSION: These findings suggest plastic surgeons may consider performing autologous breast reconstruction early for select patients, before 3 months following PMRT without increasing postoperative morbidity.

Postoperative hand therapy and the 2018 Medicare therapy cap repeal: Appraising cost and use changes.

BACKGROUND: Therapy use is common following carpal tunnel release (CTR), trigger finger release, ganglion cyst excision, De Quervain tenosynovitis release, carpometacarpal arthroplasty, and distal radius fracture, open reduction internal fixation or percutaneous pinning (DRF). Policy that improves coverage influences the cost and use of health care services. PURPOSE: This study aims to evaluate changes to the cost and use of postoperative hand therapy by race and procedure following the repeal of a longstanding annual Medicare outpatient therapy cap. STUDY DESIGN: Retrospective cohort study. METHODS: This is a longitudinal retrospective cohort study using a quasi-experimental interrupted time series design, including patients who underwent common hand surgeries from January 1, 2016-December 31, 2019. RESULTS: This study included 203,672 patients with a mean age of 71.4 years. Neither White (1.00, 95% confidence interval [CI]: 0.999-1.007, p = 0.45) nor non-White (1.00, 95% CI: 1.00-1.01, p = 0.06) patients experienced monthly changes in therapy use before policy implementation. Therapy frequency increased following CTR (odds ratio [OR] 1.12, 95% CI: 1.11-1.14, p < 0.001), trigger finger release (OR 1.09, 95% CI: 1.07-1.10, p < 0.001), and DRF (OR 1.05, 95% CI: 1.03-1.06, p < 0.001) following implementation. CONCLUSIONS: This study found that improved coverage was associated with increased postoperative therapy use among some subsets, including CTR and DRF, suggesting the need to optimize coverage by means such as prior authorization or bundled payments, rather than only increasing coverage benefits.

Carpal Tunnel Syndrome as a Test Case for Value Assessment During the Presurgical Period: The Impact of Structure and Processes of Care.

BACKGROUND: Few performance measures assess presurgical value (quality and utilization). OBJECTIVES: Using carpal tunnel syndrome (CTS) as a case study: (1) develop a model to evaluate presurgical quality and utilization and (2) identify opportunities for value improvement. RESEARCH DESIGN: A retrospective cohort study utilizing Veterans Affairs (VA) national administrative data. SUBJECTS: Patients who were evaluated in a VA primary care clinic on at least 1 occasion for CTS and received carpal tunnel release over a 7-year period. MEASURES: We modeled facility-level performance on 2 outcomes: surgical delay (marker of quality) and number of presurgical encounters (utilization) for CTS, and examined association between patient, facility, and care process variables and performance. RESULTS: Among 41,912 Veterans undergoing carpal tunnel release at 127 VA medical centers, the median facility-level predicted probability of surgical delay was 48%, with 16 (13%) facilities having significantly less delay than the median and 13 (10%) facilities having greater delay. The median facility-level predicted number of presurgical encounters was 8.8 visits, with 22 (17%) facilities having significantly fewer encounters and 22 (17%) facilities having more. Care processes had a stronger association with both outcomes than structural variables included in the models. Processes associated with the greatest deviations in predicted delay and utilization included receipt of repeat electrodiagnostic testing, use of 2 or more nonoperative treatments, and community referral outside of VA. CONCLUSIONS: Using CTS as a test case, this study demonstrates the potential to assess presurgical value and identify modifiable care processes associated with presurgical delay and utilization performance.

Cost-effectiveness of surgical treatment of thumb carpometacarpal joint arthritis: a value of information study.

BACKGROUND: Thumb carpometacarpal (CMC) joint arthritis is one of the most prevalent arthritic conditions commonly treated with trapeziectomy alone or trapeziectomy with ligament reconstruction and tendon interposition (LRTI). We evaluate the cost-effectiveness and value of perfect and sample information of trapeziectomy alone, LRTI, and non-operative treatment. METHODS: A societal perspective decision tree was modeled. To understand the value of future research in comparing quality-of-life after trapeziectomy, LRTI, and non-operative management we characterized uncertainty by fitting distributions to EQ-5D utility data published from the United Kingdom hand surgery registry. We used Monte Carlo simulation for the probabilistic sensitivity analysis and to evaluate the value of perfect and sample information. RESULTS: Both trapeziectomy alone and LRTI were cost-effective compared to non-operative management ($2,540 and $3,511/QALY respectively). Trapeziectomy alone (base case total cost $8,251, QALY 14.08) was dominant compared to LRTI (base case total cost $8,798, QALY 13.34). However, probabilistic sensitivity analysis suggested there is a 12.5% chance LRTI may be preferred at a willingness-to-pay of $50,000/QALY. Sensitivity analysis revealed postoperative utilities are the most influential factors in determining cost-effectiveness. The value of perfect information was approximately $1,503/person. A study evaluating the quality-of-life of 1,000 patients in each arm undergoing trapeziectomy alone or LRTI could provide an expected $1,117 of information value. With approximately 40,000 CMC arthroplasties performed each year in the U.S., the annual value is close to $45 million. CONCLUSIONS: Trapeziectomy without LRTI appears to be the most cost-effective procedure in treating late-stage CMC arthritis and should be considered as first-line surgical treatment. There is substantial societal value in conducting additional research to better understand the relative quality-of-life improvements gained from these two common hand surgeries.

Hemoperfusion with Seraph 100 Microbind Affinity Blood Filter Unlikely to Require Increased Antibiotic Dosing: A Simulations Study Using a Pharmacokinetic/Pharmacodynamic Approach.

INTRODUCTION: The Seraph® 100 Microbind® Affinity Blood Filter (Seraph 100) is a hemoperfusion device that can remove pathogens from central circulation. However, the effect of Seraph 100 on achieving pharmacodynamic (PD) targets is not well described. We sought to determine the impact of Seraph 100 on ability to achieve PD targets for commonly used antibiotics. METHODS: Estimates of Seraph 100 antibiotic clearance were obtained via literature. For vancomycin and gentamicin, published pharmacokinetic models were used to explore the effect of Seraph 100 on ability to achieve probability of target attainment (PTA). For meropenem and imipenem, the reported effect of continuous kidney replacement therapy (CKRT) on achieving PTA was used to extrapolate decisions for Seraph 100. RESULTS: Seraph 100 antibiotic clearance is likely less than 0.5 L/h for most antibiotics. Theoretical Seraph 100 clearance up to 0.5 L/h and 2 L/h had a negligible effect on vancomycin PTA in virtual patients with creatinine clearance (CrCl) = 14 mL/min and CrCl >14 mL/min, respectively. Theoretical Seraph 100 clearance up to 0.5 L/h and 2 L/h had a negligible effect on gentamicin PTA in virtual patients with CrCl = 120 mL/min and CrCl <60 mL/min, respectively. CKRT intensity resulting in antibiotic clearance up to 2 L/h generally does not require dose increases for meropenem or imipenem. As Seraph 100 is prescribed intermittently and likely contributes far less to antibiotic clearance, dose increases would also not be required. CONCLUSION: Seraph 100 clearance of vancomycin, gentamicin, meropenem, and imipenem is likely clinically insignificant. There is insufficient evidence to recommend increased doses. For aminoglycosides, we recommend extended interval dosing and initiating Seraph 100 at least 30 min to 1 h after completion of infusion to avoid the possibility of interference with maximum concentrations.

Longitudinal association between children's mastery motivation and cognitive school readiness: Executive functioning and social-emotional competence as potential mediators.

This study investigated the direct relationships between kindergarten children's object and social mastery motivation and future cognitive school readiness and the indirect relationships mediated through executive functioning and social-emotional competence in the school context. The participants were 103 Hong Kong kindergarten children (45.6% girls; mean age = 60.4 months) and their teachers. The teachers reported the children's demographic information and object and social mastery motivation at Time 1 (in the middle of the school year). They rated the children's executive functioning, social-emotional competence and cognitive school readiness at Time 2 (at the end of the school year). The results from the path analysis model revealed that the children's object mastery motivation at Time 1, but not their social mastery motivation, directly predicted their cognitive school readiness at Time 2. The indirect relationships between (a) object mastery motivation at Time 1 and cognitive school readiness at Time 2 mediated through executive functioning (indirect effect: ß =.32, SE =.05, p <.001) and (b) social mastery motivation at Time 1 and cognitive school readiness at Time 2 mediated through social-emotional competence (indirect effect: ß =.09, SE =.03, p <.01) were significant. The findings highlight the differential roles of object and social mastery motivation in predicting children's cognitive school readiness and propose children's executive functioning and social-emotional competence as processes mediating the relationships. The results also suggest the desirability of providing kindergarten children with extensive play opportunities and materials to support their mastery motivation and cognitive school readiness.

What are the cognitive-linguistic profiles and subtypes of Chinese adolescents with dyslexia?

While research has identified multiple deficits that may lead to dyslexia, the profiles of adolescents with dyslexia and dyslexia subtypes are yet fully understood. This study examined the profiles of Chinese adolescents with dyslexia and identified dyslexia subtypes. Adolescents from grades 7 to 9 (n = 184, 92 with dyslexia) were evaluated on morphological skills, visual-orthographic knowledge, rapid naming, working memory, word reading, word spelling, reading fluency and reading comprehension. The results revealed that adolescents with dyslexia performed less well on the cognitive-linguistic and literacy measures than typically developing adolescents. A logistic regression analysis also showed that morphological skills, visual-orthographic knowledge and rapid naming were significantly predictive of dyslexia status. Using cluster analysis and guided by the multiple deficit hypothesis, this study identified four dyslexia subtypes: morphological deficit, visual-orthographic knowledge deficit, rapid naming deficit and global deficit showing multiple cognitive-linguistic and literacy problems. Understanding the profiles and subtypes of dyslexia could enable educational psychologists and educators to select appropriate assessment measures and develop intervention strategies to support the learning of Chinese adolescents with dyslexia.

Can we do better at measuring patient-reported outcomes after cranioplasty? A systematic review.

Measuring quality of life (QOL) after cranioplasty is increasingly evident as a necessary component of patient-centered care. For data to be useful in clinical decision-making and approval of new therapies, studies must utilize valid and reliable instruments. Our objective was to critically appraise studies evaluating QOL in adult cranioplasty patients and determine validity and relevance of the patient-reported outcome measures (PROMs) used. Electronic databases of PubMed, Embase, CINAHL, and PsychINFO were used to identify PROMs measuring QOL in adult patients with cranioplasty. The methodological approach, cranioplasty outcomes, and domains measured by the PROMs were extracted and summarized descriptively. A content analysis of the identified PROMs was completed to identify the concepts measured. From 2236 articles identified, 17 articles containing eight QOL PROMs met the inclusion criteria. None of the PROMs was specifically validated or developed for adults undergoing cranioplasty. The QOL domains included physical health, psychological health, social health, and general QOL. These four domains encompassed 216 total items among the PROMs. Appearance was only assessed in two PROMs. To our knowledge, there are currently no validated PROMs that comprehensively measure appearance, facial function, and adverse effects in adults undergoing cranioplasty. There is an urgent need to develop PROMs to measure QOL outcomes rigorously and comprehensively in this patient population to inform clinical care, research, and quality improvement initiatives. Findings from this systematic review will be used to derive an outcome instrument containing important concepts related to QOL in patients who undergo cranioplasty.

Are Observational Studies on Distal Radius Fracture Treatment Robust? An E-value Approach to Analysis.

BACKGROUND: Reported complication frequencies after distal radius fracture (DRF) treatment vary widely in the literature and are based mostly on observational evidence. Whether that evidence is sufficiently robust to use in practice is controversial. The E-value is an innovative sensitivity analysis that quantitates the robustness of observational evidence against unmeasured confounders, whereby a greater E-value usually implies more robust evidence and vice versa; with DRF complications, this approach can help guide readers to a more confident interpretation of the available evidence. QUESTIONS/PURPOSES: In this study, we sought (1) to compare the complication frequencies among different DRF treatment modalities, and (2) to evaluate the robustness of these observational studies using the E-value as an index for unmeasured confounding. METHODS: We searched PubMed, Embase, and SCOPUS for observational studies on the management of DRFs that were published from January 2001 to July 2021 with the last database search performed on July 31, 2021. All articles that compared different DRF treatment modalities with reported complication frequencies were included to accurately capture the quality of the observational studies in research about DRF. Risk ratios (RRs) of the overall complication and major complication risks were calculated for each subgroup comparison: volar plating versus dorsal plating, casting, external fixation, and percutaneous K-wire fixation. The RRs and their corresponding lower limits of the 95% confidence intervals (CIs) were used to derive the E-values. E-values can have a minimum possible value of 1, which signifies that the treatment-outcome association is not strong and can readily be overturned by unmeasured confounders. By contrast, a large E-value means that the observed treatment-outcome association is robust against unmeasured confounders. We averaged RRs and E-values for the effect estimates and lower limits of CIs across studies in each treatment comparison group. We identified 36 comparative observational studies that met the inclusion criteria. Seven studies compared volar with dorsal plating techniques. Volar plating was also compared with casting (eight studies), external fixation (15 studies), and percutaneous K-wire fixation (six studies). RESULTS: Total and major complication risks did not differ among different DRF treatments. The mean RRs for total and major complications were 1.2 (95% CI 0.4 to 3.9; p = 0.74) and 1.8 (95% CI 0.4 to 11.4; p = 0.52) for the volar versus dorsal plating group; 1.2 (95% CI 0.3 to 11.2; p = 0.87) and 1.5 (95% CI 0.3 to 14.9; p = 0.74) for the volar plating versus casting group; 0.6 (95% CI 0.2 to 2.2; p = 0.33) and 0.8 (95% CI 0.2 to 6.7; p = 0.86) for the volar plating versus external fixation group; and 0.6 (95% CI 0.2 to 2.6; p = 0.47) and 0.7 (95% CI 0.2 to 4.0; p = 0.67) for the volar plating versus K-wire fixation group. The mean E-values for total and major complication frequencies for the between-group comparison ranged from 3.1 to 5.8; these were relatively large in the context of a known complication risk factor, such as high-energy impact (RR 3.2), suggesting a reasonable level of robustness against unmeasured confounding. However, the E-values for lower limits of CIs remained close to 1, which indicates the observed complication frequencies in these studies were likely to have been influenced by unmeasured confounders. CONCLUSION: Complication frequencies did not differ among different DRF treatment modalities, but the observed complication frequencies from most comparative observational studies were less robust against potential unmeasured confounders. The E-value method, or another type of sensitivity analysis, should be implemented in observational hand surgery research at the individual-study level to facilitate assessment of robustness against potential unmeasured confounders. LEVEL OF EVIDENCE: Level III, therapeutic study.

Can a Deep Learning Algorithm Improve Detection of Occult Scaphoid Fractures in Plain Radiographs? A Clinical Validation Study.

BACKGROUND: Occult scaphoid fractures on initial radiographs of an injury are a diagnostic challenge to physicians. Although artificial intelligence models based on the principles of deep convolutional neural networks (CNN) offer a potential method of detection, it is unknown how such models perform in the clinical setting. QUESTIONS/PURPOSES: (1) Does CNN-assisted image interpretation improve interobserver agreement for scaphoid fractures? (2) What is the sensitivity and specificity of image interpretation performed with and without CNN assistance (as stratified by type: normal scaphoid, occult fracture, and apparent fracture)? (3) Does CNN assistance improve time to diagnosis and physician confidence level? METHODS: This survey-based experiment presented 15 scaphoid radiographs (five normal, five apparent fractures, and five occult fractures) with and without CNN assistance to physicians in a variety of practice settings across the United States and Taiwan. Occult fractures were identified by follow-up CT scans or MRI. Participants met the following criteria: Postgraduate Year 3 or above resident physician in plastic surgery, orthopaedic surgery, or emergency medicine; hand fellows; and attending physicians. Among the 176 invited participants, 120 completed the survey and met the inclusion criteria. Of the participants, 31% (37 of 120) were fellowship-trained hand surgeons, 43% (52 of 120) were plastic surgeons, and 69% (83 of 120) were attending physicians. Most participants (73% [88 of 120]) worked in academic centers, whereas the remainder worked in large, urban private practice hospitals. Recruitment occurred between February 2022 and March 2022. Radiographs with CNN assistance were accompanied by predictions of fracture presence and gradient-weighted class activation mapping of the predicted fracture site. Sensitivity and specificity of the CNN-assisted physician diagnoses were calculated to assess diagnostic performance. We calculated interobserver agreement with the Gwet agreement coefficient (AC1). Physician diagnostic confidence was estimated using a self-assessment Likert scale, and the time to arrive at a diagnosis for each case was measured. RESULTS: Interobserver agreement among physicians for occult scaphoid radiographs was higher with CNN assistance than without (AC1 0.42 [95% CI 0.17 to 0.68] versus 0.06 [95% CI 0.00 to 0.17], respectively). No clinically relevant differences were observed in time to arrive at a diagnosis (18 ± 12 seconds versus 30 ± 27 seconds, mean difference 12 seconds [95% CI 6 to 17]; p < 0.001) or diagnostic confidence levels (7.2 ± 1.7 seconds versus 6.2 ± 1.6 seconds; mean difference 1 second [95% CI 0.5 to 1.3]; p < 0.001) for occult fractures. CONCLUSION: CNN assistance improves physician diagnostic sensitivity and specificity as well as interobserver agreement for the diagnosis of occult scaphoid fractures. The differences observed in diagnostic speed and confidence is likely not clinically relevant. Despite these improvements in clinical diagnoses of scaphoid fractures with the CNN, it is unknown whether development and implementation of such models is cost effective. LEVEL OF EVIDENCE: Level II, diagnostic study.

Electrodiagnostic Predictors of Outcomes After In Situ Decompression of the Ulnar Nerve.

PURPOSE: Patients with severe ulnar neuropathy at the elbow frequently experience suboptimal surgical outcomes. Clinical symptoms alone may not accurately represent the severity of underlying nerve injury, calling for objective assessment tools, such as electrodiagnostic studies. The goal of our study was to determine whether specific electrodiagnostic parameters can be used to predict the outcomes after in situ decompression of the ulnar nerve. METHODS: This prospective study enrolled consecutive patients aged ≥18 years diagnosed with ulnar neuropathy at the elbow. Patients completed a baseline battery of motor, sensory, functional, and electrodiagnostic tests before undergoing in situ decompression of the ulnar nerve. They were reassessed at 6 weeks, 3 months, 6 months, and 12 months after surgery. Forty-two patients completed at least 2 follow-up assessments and were included in the study. RESULTS: When controlling for other electrodiagnostic measurements and demographic factors, none of the electrodiagnostic parameters were predictive of outcomes at 12 months after surgery. Patients with decreased compound muscle action potential amplitudes demonstrated slower trends of recovery in grip strength, pinch strength, and overall scores on the Michigan Hand Outcomes Questionnaire as well as its function, work, and activities of daily living subscales, Disabilities of the Arm, Shoulder, and Hand questionnaire, and the Carpal Tunnel Questionnaire. Decreased motor nerve conduction velocity was predictive of slower recovery of 2-point discrimination and pinch strength. CONCLUSIONS: Compound muscle action potential amplitude, but not other conventional electrodiagnostic parameters, was predictive of functional outcomes after in situ decompression of the ulnar nerve. This parameter should play a role in determining the timing and prognosis of treatment for ulnar neuropathy at the elbow. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Does Surgical Intensity Correlate With Opioid Prescribing?: Classifying Common Surgical Procedures.

OBJECTIVE: To examine the relationship between aspects of surgical intensity and postoperative opioid prescribing. SUMMARY OF BACKGROUND DATA: Despite the emergence of postoperative prescribing guidelines, recommendations are lacking for many procedures. identifying a framework based on surgical intensity to guide prescribing for those procedures in which guidelines may not exist could inform postoperative prescribing. METHODS: We used clustering analysis with 4 factors of surgical intensity (intrinsic cardiac risk, pain score, median operative time, and work relative value units) to devise a classification system for common surgical procedures. We used IBM MarketScan Research Database (2010-2017) to examine the correlation between this framework with initial opioid prescribing and rates of refill for each cluster of procedures. RESULTS: We examined 2,407,210 patients who underwent 128 commonly performed surgeries. Cluster analysis revealed 5 ordinal clusters by intensity: low, mid-low, mid, mid-high, and high. We found that as the cluster-order increased, the median amount of opioid prescribed increased: 150 oral morphine equivalents (OME) for low-intensity, 225 OME for mid-intensity, and 300 OME for high-intensity surgeries. Rates of refill increased as surgical intensity also increased, from 17.4% for low, 26.4% for mid, and 48.9% for high-intensity procedures. The odds of refill also increased as cluster-order increased; relative to low-intensity procedures, high-intensity procedures were associated with 4.37 times greater odds of refill. CONCLUSION: Surgical intensity is correlated with initial opioid prescribing and rates of refill. Aspects of surgical intensity could serve as a guide for procedures in which guidelines based on patient-reported outcomes are not available.

An analysis of early volume resuscitation and the association with prolonged mechanical ventilation.

BACKGROUND: Previous studies have found that intravenous fluid administration within the first 24 h may be associated with prolonged mechanical ventilation (PMV). We examined the association between initial 24 h fluids and PMV in combat casualties. METHODS: This is a secondary analysis of a previously described dataset from the Department of Defense Trauma Registry (DODTR). We included casualties with at least 24 h on the ventilator and no significant traumatic brain injury. The definition of PMV and associations were constructed using univariable and multivariable logistic regression models. RESULTS: We identified 1508 casualties available for analysis for this study - 1275 in the non-PMV cohort (<9 days on ventilator vs. 233 in the PMV cohort (≥9 days on ventilator). Explosives comprised the most common mechanism of injury for both groups (72% vs. 75%) followed by firearms (21% vs. 16%). The composite injury severity score (ISS) was lower in the non-PMV cohort (18 vs. 30, p < .001). There were lower volumes of all resuscitation fluid within the first 24 h in the non-PMV cohort. When adjusting for composite ISS and mechanism of injury in a multivariable logistic regression model with PMV as the outcome, crystalloid volume (unit odds ratio [UOR] 1.07) and colloid volume (UOR 1.03) were both associated with PMV. CONCLUSIONS: We found that volume of resuscitation fluids were substantially higher in the PMV cohort. Our findings suggest the need for caution with the routine use of crystalloid and colloid in the first 24 h of resuscitation.