Low-Intensity Pulsed Ultrasound Versus Sham in the Treatment of Operatively Managed Scaphoid Nonunions: The SNAPU Randomized Controlled Trial.

BACKGROUND: The primary goal after open reduction and internal fixation of an established scaphoid nonunion is to achieve union. Low-intensity pulsed ultrasound (LIPUS) has been reported to increase the rate of union and to decrease the time to union for multiple fractures and nonunions in clinical and animal models. The evidence for LIPUS in the treatment of scaphoid nonunion, however, is sparse. The aim of this study was to assess whether active LIPUS (relative to sham LIPUS) accelerates the time to union following surgery for scaphoid nonunion. METHODS: Adults with a scaphoid nonunion indicated for surgery were recruited for a multicenter, prospective, double-blinded randomized controlled trial. After surgery, patients self-administered activated or sham LIPUS units beginning at their first postoperative visit. The primary outcome was the time to union on serial computed tomography (CT) scans starting 6 to 8 weeks postoperatively. Secondary outcomes included patient-reported outcome measures, range of motion, and grip strength. RESULTS: A total of 142 subjects completed the study (69 in the active LIPUS group and 73 in the sham group). The average age was 27 years, and the cohort was 88% male. There was no difference in time to union (p = 0.854; hazard ratio, 0.965; 95% confidence interval, 0.663 to 1.405). Likewise, there were no differences between the active LIPUS and sham groups with respect to any of the secondary outcomes, except for wrist flexion at baseline (p = 0.008) and at final follow-up (p = 0.043). CONCLUSIONS: Treatment with LIPUS had no effect on reducing time to union in patients who underwent surgical fixation of established scaphoid nonunions. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Risk Factors for the Development of Persistent Scaphoid Non-Union After Surgery for an Established Non-Union.

BACKGROUND: Between 2014 and 2020, candidates for scaphoid non-union (SNU) surgery were enrolled in a prospective randomized trial (Scaphoid Nonunion and Low Intensity Pulsed Ultrasound [SNAPU] trial) evaluating the effect of low-intensity pulsed ultrasound on postoperative scaphoid healing. At trial completion, 114/134 (85%) of these patients went on to union, and 20/134 (15%) went on to persistent SNU (PSNU). The purpose of this study was to use this prospectively gathered data to identify patient-, fracture-, and surgery-specific risk factors that may be predictive of PSNU in patients who undergo surgery for SNU. METHODS: Data were extracted from the SNAPU trial database. The inclusion and exclusion criteria of this study were the same as that of the SNAPU trial. Nineteen patient-, fracture-, and surgery-specific risk factors were determined a priori. A stepwise multivariable logistic regression model was used to identify independent risk factors for PSNU. RESULTS: Three risk factors were found to be independently significant predictors of PSNU: age at the time of surgery, dominant hand injury, and previous surgery on the affected scaphoid. With every decade of a patient's life, dominant hand injury, and previous scaphoid surgery, the odds of union are reduced by 1.72 times, 7.35 times, and 4.24 times, respectively. CONCLUSION: We identified three independent risk factors for PSNU: age at SNU surgery, dominant hand injury, and previous surgery on the affected scaphoid. The findings of this study are significant and may contribute to shared decision-making and prognostication between the patient, surgeon, and affiliated members of their care team.

Learning from the early careers of master clinicians.

BACKGROUND: Master clinicians are recognized as multidimensional experts in clinical medicine. Studying their formative clinical activities could generate insights to guide medical trainees and early career clinicians. OBJECTIVES: To investigate which early career activities were adopted more commonly by master clinicians than their matched peers and to characterize master clinicians' early career activities across institutions and specialties. SUBJECTS AND METHODS: We surveyed master clinicians at seven medical centres about their early career activities. For master clinicians in the Department of Medicine (DOM), we also surveyed matched internist peers. RESULTS: Of 150 master clinician respondents, 65% were internists (DOM); 35% practiced in other specialties. Compared to their internist peers, there was a trend toward internist master clinicians reading more about their patients' conditions (6.0 vs. 4.8 h per week), reading more case reports (4.0 vs. 2.1 per month), engaging in more frequent teaching duties and devoting less time to research. CONCLUSIONS: The early career activities identified in this study can be adopted by clinicians pursuing clinical excellence and promoted by training programs that seek to foster life-long learning.

Evaluating a low anion gap: A practical approach.

In teaching and in practice, little attention is given to a low anion gap. This oversight can result in a missed opportunity to diagnose acute or chronic disorders requiring treatment. In this article, we review the constituents of the anion gap, build a differential diagnosis for a low anion gap using case examples, and provide a stepwise approach to diagnostic testing to evaluate this abnormal finding.

Clinician Testing and Treatment Thresholds for Management of Urinary Tract Infection.

Greater understanding of clinical decision thresholds may improve inappropriate testing and treatment of urinary tract infection (UTI). We used a survey of clinicians to examine UTI decision thresholds. Although overestimates of UTI occurred, testing and treatment thresholds were generally rational, were lower than previously reported, and differed by type of clinician.

Characterization of an HNA aptamer suggests a non-canonical G-quadruplex motif.

Nucleic acids not only form the basis of heredity, but are increasingly a source of novel nano-structures, -devices and drugs. This has spurred the development of chemically modified alternatives (xeno nucleic acids (XNAs)) comprising chemical configurations not found in nature to extend their chemical and functional scope. XNAs can be evolved into ligands (XNA aptamers) that bind their targets with high affinity and specificity. However, detailed investigations into structural and functional aspects of XNA aptamers have been limited. Here we describe a detailed structure-function analysis of LYS-S8-19, a 1',5'-anhydrohexitol nucleic acid (HNA) aptamer to hen egg-white lysozyme (HEL). Mapping of the aptamer interaction interface with its cognate HEL target antigen revealed interaction epitopes, affinities, kinetics and hot-spots of binding energy similar to protein ligands such as anti-HEL-nanobodies. Truncation analysis and molecular dynamics (MD) simulations suggest that the HNA aptamer core motif folds into a novel and not previously observed HNA tertiary structure, comprising non-canonical hT-hA-hT/hT-hT-hT triplet and hG4-quadruplex structures, consistent with its recognition by two different G4-specific antibodies.

A Clinical Reasoning-Encoded Case Library Developed through Natural Language Processing.

IMPORTANCE: Case reports that externalize expert diagnostic reasoning are utilized for clinical reasoning instruction but are difficult to search based on symptoms, final diagnosis, or differential diagnosis construction. Computational approaches that uncover how experienced diagnosticians analyze the medical information in a case as they formulate a differential diagnosis can guide educational uses of case reports. OBJECTIVE: To develop a "reasoning-encoded" case database for advanced clinical reasoning instruction by applying natural language processing (NLP), a sub-field of artificial intelligence, to a large case report library. DESIGN: We collected 2525 cases from the New England Journal of Medicine (NEJM) Clinical Pathological Conference (CPC) from 1965 to 2020 and used NLP to analyze the medical terminology in each case to derive unbiased (not prespecified) categories of analysis used by the clinical discussant. We then analyzed and mapped the degree of category overlap between cases. RESULTS: Our NLP algorithms identified clinically relevant categories that reflected the relationships between medical terms (which included symptoms, signs, test results, pathophysiology, and diagnoses). NLP extracted 43,291 symptoms across 2525 cases and physician-annotated 6532 diagnoses (both primary and related diagnoses). Our unsupervised learning computational approach identified 12 categories of medical terms that characterized the differential diagnosis discussions within individual cases. We used these categories to derive a measure of differential diagnosis similarity between cases and developed a website ( universeofcpc.com ) to allow visualization and exploration of 55 years of NEJM CPC case series. CONCLUSIONS: Applying NLP to curated instances of diagnostic reasoning can provide insight into how expert clinicians correlate and coordinate disease categories and processes when creating a differential diagnosis. Our reasoning-encoded CPC case database can be used by clinician-educators to design a case-based curriculum and by physicians to direct their lifelong learning efforts.

The cognitive apprenticeship: advancing reasoning education by thinking aloud.

Teaching clinical reasoning has long challenged educators because it requires familiarity with reasoning concepts, experience with describing thinking, and comfort with exposing uncertainty and error. We propose that teachers adopt the cognitive apprenticeship model and a method of disclosing uncertainty known as intellectual streaking. These approaches reflect a shift in the educator's mindset from transmitting medical knowledge to broadcasting cognition. We provide several examples to guide the adoption of these strategies and make recommendations for teachers and training programs to improve the teaching of clinical reasoning.

Mission Critical: Reimagining Promotion for Clinician-Educators.

Academic clinician-educators who teach health professions trainees and lead educational programs have been penalized by the mismatch between their daily contributions to the academic mission and traditional promotion criteria focused on peer-reviewed publications and external reputation. Despite two decades of incremental approaches, inconsistency and inequity persist in the promotion process for clinician-educators. The authors propose five steps to mark a new approach to academic advancement for clinician-educators: (1) elevate the scholarly approach to teaching over peer-reviewed publications; (2) allow clinician-educators to identify an area of focus; (3) broaden the evidence for educational excellence; (4) prioritize internal referees; and (5) increase clinician-educator representation on promotion committees. Achieving meaningful change requires transforming entrenched traditions and policies at multiple levels. Changes that advance equity are necessary to retain academic faculty members who train the next generation of health professionals.

Diagnostic Schemas: Form and Function.

Diagnostic schemas are frameworks that depict organized clinical knowledge and serve as a bridge between problem representation and differential diagnosis generation. Schema-based problem solving is increasingly used among clinician educators and is widely featured in digital media. We examine the origins of schemas and their theoretical background, review existing literature on their applications in medicine, and explore their utility for learners and teachers.

Efficient synthesis and replication of diverse sequence libraries composed of biostable nucleic acid analogues.

Functional nucleic acids can be evolved in vitro using cycles of selection and amplification, starting from diverse-sequence libraries, which are typically restricted to natural or partially-modified polymer chemistries. Here, we describe the efficient DNA-templated synthesis and reverse transcription of libraries entirely composed of serum nuclease resistant alternative nucleic acid chemistries validated in nucleic acid therapeutics; locked nucleic acid (LNA), 2'-O-methyl-RNA (2'OMe-RNA), or mixtures of the two. We evaluate yield and diversity of synthesised libraries and measure the aggregate error rate of a selection cycle. We find that in addition to pure 2'-O-methyl-RNA and LNA, several 2'OMe-RNA/LNA blends seem suitable and promising for discovery of biostable functional nucleic acids for biomedical applications.