Effect of Reflectance Confocal Microscopy for Suspect Lesions on Diagnostic Accuracy in Melanoma: A Randomized Clinical Trial.

Importance: Previous systematic reviews and meta-analyses have concluded that given data paucity, a comparison of reflectance confocal microscopy (RCM) with dermoscopy is complex. They recommend comparative prospective studies in a real-world setting of suspect lesions. Objective: To test the hypothesis that RCM reduces unnecessary lesion excision by more than 30% and identifies all melanoma lesions thicker than 0.5 mm at baseline. Design, Setting, and Participants: This randomized clinical trial included 3165 patients enrolled from 3 dermatology referral centers in Italy between January 2017 and December 2019, with a mean (SD) follow-up of 9.6 (6.9) months (range, 1.9-37.0 months). The consecutive sample of 3165 suspect lesions determined through dermoscopy were eligible for inclusion (10 patients refused). Diagnostic analysis included 3078 patients (48 lost, 39 refused excision). Data were analyzed between April and September 2021. Interventions: Patients were randomly assigned 1:1 to standard therapeutic care (clinical and dermoscopy evaluation) with or without adjunctive RCM. Information available guided prospective clinical decision-making (excision or follow-up). Main Outcomes and Measures: Hypotheses were defined prior to study initiation. All lesions excised (baseline and follow-up) were registered, including histopathological diagnoses/no change at dermoscopy follow-up (with or without adjunctive RCM). Number needed to excise (total number of excised lesions/number of melanomas) and Breslow thickness of delayed diagnosed melanomas were calculated based on real-life, prospective, clinical decision-making. Results: Among the 3165 participants, 1608 (50.8%) were male, and mean (SD) age was 49.3 (14.9) years. When compared with standard therapeutic care only, adjunctive RCM was associated with a higher positive predictive value (18.9 vs 33.3), lower benign to malignant ratio (3.7:1.0 vs 1.8:1.0), and a number needed to excise reduction of 43.4% (5.3 vs 3.0). All lesions (n = 15) with delayed melanoma diagnoses were thinner than 0.5 mm. Conclusions and Relevance: This randomized clinical trial shows that adjunctive use of RCM for suspect lesions reduces unnecessary excisions and assures the removal of aggressive melanomas at baseline in a real-life, clinical decision-making application for referral centers with RCM. Trial Registration: ClinicalTrials.gov Identifier: NCT04789421.

Uncomplicated Distal Radius Fractures: An Opportunity to Reduce Emergency Medicine Opioid Prescribing?

OBJECTIVES: To assess emergency physician prescribing for simple extremity fractures-specifically, distal radius fractures-and describe the opportunity for reducing opioid prescribing. METHODS: An electronic survey was distributed to 1238 emergency physicians employed by a nationwide practice serving 220 sites in 20 states. The survey presented two plain film views of a simple Colles fracture and asked: "For the last patient you discharged . . . with the above injury, which pain medications did you prescribe or recommend?" Responses were collected using a clickable checklist of common opioid and nonopioid pain medications. Respondents also specified the number of days covered by any prescription. We assessed associations between physician characteristics and opioid prescribing using the χ2 test, the Wilcoxon rank-sum test, and multivariable regression models. RESULTS: Responses were received from 447 (36%) physicians working in 18 states; 93% were trained in emergency medicine, 33% worked at academic sites, 68% had site volumes between 25,000 and 75,000, and the median experience was 10 (interquartile range 5-19) years. Overall, 92% (95% confidence interval 89%-95%) had prescribed an opioid for a median of 3 (interquartile range 3-4) days. The most commonly prescribed opioids were hydrocodone/acetaminophen (55%) and oxycodone/acetaminophen (20%). Physicians at academic sites prescribed opioids less frequently than those at nonacademic sites (88% vs 94%), but in multivariable regression there were no significant associations between physician characteristics and opioid prescribing. CONCLUSIONS: Emergency physicians commonly prescribe opioids for simple distal radius fractures. This represents a potential opportunity to reduce opioid prescribing.

Serum Biomarker Profile Including CCL1, CXCL10, VEGF, and Adenosine Deaminase Activity Distinguishes Active From Remotely Acquired Latent Tuberculosis.

Introduction: There is an urgent medical need to differentiate active tuberculosis (ATB) from latent tuberculosis infection (LTBI) and prevent undertreatment and overtreatment. The aim of this study was to identify biomarker profiles that may support the differentiation between ATB and LTBI and to validate these signatures. Materials and Methods: The discovery cohort included adult individuals classified in four groups: ATB (n = 20), LTBI without prophylaxis (untreated LTBI; n = 20), LTBI after completion of prophylaxis (treated LTBI; n = 20), and healthy controls (HC; n = 20). Their sera were analyzed for 40 cytokines/chemokines and activity of adenosine deaminase (ADA) isozymes. A prediction model was designed to differentiate ATB from untreated LTBI using sparse partial least squares (sPLS) and logistic regression analyses. Serum samples of two independent cohorts (national and international) were used for validation. Results: sPLS regression analyses identified C-C motif chemokine ligand 1 (CCL1), C-reactive protein (CRP), C-X-C motif chemokine ligand 10 (CXCL10), and vascular endothelial growth factor (VEGF) as the most discriminating biomarkers. These markers and ADA(2) activity were significantly increased in ATB compared to untreated LTBI (p ≤ 0.007). Combining CCL1, CXCL10, VEGF, and ADA2 activity yielded a sensitivity and specificity of 95% and 90%, respectively, in differentiating ATB from untreated LTBI. These findings were confirmed in the validation cohort including remotely acquired untreated LTBI participants. Conclusion: The biomarker signature of CCL1, CXCL10, VEGF, and ADA2 activity provides a promising tool for differentiating patients with ATB from non-treated LTBI individuals.

[De-escalation strategies in differentiated thyroid cancer]. / Les stratégies de désescalade pour les cancers différenciés de la thyroïde.

Thyroid cancer runs the gamut from indolent micropapillary carcinoma to highly aggressive metastatic disease. Today, using prognostic algorithms, treatment and follow-up can be tailored to each patient in order to decrease overtreatment and over-medicalization of indolent disease. Active surveillance of papillary thyroid carcinoma less than 1cm avoids surgery and thyroid hormone replacement in a large proportion of patient whose tumors remain stable for years. Total thyroidectomy, once a dogma in the treatment of all thyroid cancer, is being supplanted by thyroid lobectomy for low-risk cancers, thereby decreasing the surgical risks involved and improving patients' quality of life. Indications for prophylactic central neck dissection, once mandatory, are now being adapted to the risk of cancer recurrence. Radioactive iodine therapy, also previously mandatory for all, is now only employed according to risk factors and expected outcomes. Follow-up is also being tailored to risk factors for recurrence, with less frequent visits and less use of ultrasound and scintigraphy. For more advanced disease, molecular therapies tailored to somatic mutations are opening opportunities for redifferentiation of aggressive tumors which become amenable to radioactive iodine therapy which carries fewer side effects than other systemic therapies. These advances in the management of thyroid cancer with a personalized approach and de-escalation of treatment and follow-up are improving the way we treat thyroid cancer, avoiding overtreatment and improving patients' quality of life.

Telemetry Overuse and the Effect of Educational and Electronic Health Record-Based Interventions on an Academic Internal Medicine Ward.

OBJECTIVES: Guidelines for appropriate use of telemetry recommend monitoring for specific patient populations; however, many hospitalized patients receive telemetry monitoring without an indication. Clinical data and outcomes associated with nonindicated monitoring are not well studied. The objectives of our study were to evaluate the impact of an education and an order entry intervention on telemetry overuse and to identify the diagnoses and telemetry-related outcomes of patients who receive telemetry monitoring without guidelines indication. METHODS: A retrospective cohort study of hospitalized patients on internal medicine (IM) wards between 2015 and 2018 examining the effects of educational and order entry interventions at an academic urban medical center. A baseline cohort examining telemetry use was established. This was followed by the delivery of IM resident educational sessions regarding telemetry guidelines. In a subsequent intervention, the telemetry order entry system was modified with a constraint to require American Heart Association guidelines justification. RESULTS: Across all of the cohorts, 51% (n = 141) of patients lacked a guidelines-specified indication. These patients had variable diagnoses. The educational intervention alone did not result in significant differences in telemetry use by IM residents. The order entry intervention resulted in a significant increase in the proportion of guidelines-indicated patients and a decrease in nonindicated patients on telemetry. No safety events were noted in any group. CONCLUSIONS: A telemetry order entry system modification implemented following an educational intervention is more likely to reduce telemetry use than an educational intervention alone in IM resident practice. A variety of patients are monitored without evidence of need; therefore, the clinical impact of telemetry reduction is unlikely to be harmful.

Pneumatosis intestinalis and porto-mesenteric venous gas: a multicenter study.

BACKGROUND: Estimating the prognosis of patients with pneumatosis intestinalis (PI) and porto-mesenteric venous gas (PMVG) can be challenging. The purpose of this study was to refine prognostication to improve decision making in daily clinical routine. METHODS: A total of 290 patients with confirmed PI were included in the final analysis. The presence of PMVG and mortality (90d follow-up) were evaluated with regard to the influence of possible risk factors. Furthermore, a linear estimation model was devised combining significant parameters to calculate accuracies for predicting death in patients undergoing surgery by means of a defined operation point (ROC-analysis). RESULTS: Overall, 90d mortality was 55.2% (160/290). In patients with PI only, mortality was 46.5% (78/168) and increased significantly to 67.2% (82/122) in combination with PMVG (median survival: PI: 58d vs. PI and PMVG: 41d; p < 0.001). In the entire patient group, 53.5% (155/290) were treated surgically with a 90d mortality of 58.8% (91/155) in this latter group, while 90d mortality was 51.1% (69/135) in patients treated conservatively. In the patients who survived > 90d treated conservatively (24.9% of the entire collective; 72/290) PMVG/PI was defined as "benign"/reversible. PMVG, COPD, sepsis and a low platelet count were found to correlate with a worse prognosis helping to identify patients who might not profit from surgery, in this context our calculation model reaches accuracies of 97% specificity, 20% sensitivity, 90% PPV and 45% NPV. CONCLUSION: Although PI is associated with high morbidity and mortality, "benign causes" are common. However, in concomitant PMVG, mortality rates increase significantly. Our mathematical model could serve as a decision support tool to identify patients who are least likely to benefit from surgery, and to potentially reduce overtreatment in this subset of patients.

Reduction of Opioid Overprescribing and Use Following Standardized Educational Intervention: A Survey of Patient Experiences Following Anorectal Procedures.

BACKGROUND: A pilot study conducted at our institution showed that a significant amount of prescribed postoperative opioids is left unused with the potential for diversion and misuse. OBJECTIVE: This study aimed to evaluate the impact of provider- and patient-targeted educational interventions on postoperative opioid prescription and use following anorectal procedures. DESIGN: Patients were enrolled on July 2019 through March 2020 after implementing educational interventions (study) and were compared with the pilot study group (control) enrolled on August 2018 through May 2019. A telephone survey was conducted 1 week postoperatively. SETTINGS: This study was conducted at a 600-bed, safety-net hospital in southern California. PATIENTS: Adult patients undergoing ambulatory anorectal procedures were included. Patients who had undergone an examination under anesthesia, had been incarcerated, and had used opioids preoperatively were excluded. INTERVENTIONS: Educational interventions were developed based on the pilot study results. Providers received education on recommended opioid prescription quantities and a multimodal pain regimen. Standardized patient education infographics were distributed to patients pre- and postoperatively. MAIN OUTCOME MEASURES: The primary outcomes measured were total opioid prescribed, total opioid consumed, pain control satisfaction levels, and the need for additional opioid prescription. RESULTS: A total of 104 of 122 (85%) patients enrolled responded to the survey and were compared with the 112 patients included in the control group. Despite similar demographics, the study cohort was prescribed fewer milligram morphine equivalents (78.8 ± 11.3 vs 294.0 ± 33.1, p < 0.001), consumed fewer milligram morphine equivalents (23.0 ± 28.0 vs 57.1 ± 45.8, p < 0.001), and had a higher rate of nonopioid medication use (72% vs 10%, p < 0.001). The 2 groups had similar pain control satisfaction levels (4.1 ± 1.3 vs 3.9 ± 1.1 out of 5, p = 0.12) and an additional opioid prescription requirement (5% vs 4%, p = 1.0). LIMITATIONS: This study was limited by its single-center experience with specific patient population characteristics. CONCLUSION: Educational interventions emphasizing evidence-based recommended opioid prescription quantities and regimented multimodal pain regimens are effective in decreasing excessive opioid prescribing and use without compromising satisfactory pain control in patients undergoing ambulatory anorectal procedures. See Video Abstract at http://links.lww.com/DCR/B529. REDUCCIN DE LA SOBREPRESCRIPCIN Y EL USO DE OPIOIDES DESPUS DE UNA INTERVENCIN EDUCATIVA ESTANDARIZADA UNA ENCUESTA DE LAS EXPERIENCIAS EN PACIENTES POSTOPERADOS DE PROCEDIMIENTOS ANORRECTALES: ANTECEDENTES:Un estudio piloto realizado en nuestra institución mostró que una cantidad significativa de opioides posoperatorios recetados no se usa, con potencial de desvío y uso indebido.OBJETIVO:Evaluar el impacto de las intervenciones educativas dirigidas al paciente y al proveedor sobre la prescripción y el uso de opioides posoperatorios después de procedimientos anorrectales.DISEÑO:Los pacientes se incluyeron entre julio de 2019 y marzo de 2020 después de implementar intervenciones educativas (estudio) y se compararon con el grupo de estudio piloto (control) inscrito entre agosto de 2018 y mayo de 2019. Se realizó una encuesta telefónica una semana después de la cirugía.ENTORNO CLÍNICO:Hospital de 600 camas en el sur de California.PACIENTES:Pacientes adultos sometidos a procedimientos anorrectales ambulatorios. Los criterios de exclusión fueron pacientes que recibieron un examen bajo anestesia, pacientes encarcelados y uso preoperatorio de opioides.INTERVENCIONES:Se desarrollaron intervenciones educativas basadas en los resultados del estudio piloto. Los proveedores recibieron educación sobre las cantidades recomendadas de opioides recetados y un régimen multimodal para el dolor. Se distribuyeron infografías estandarizadas de educación para el paciente antes y después de la operación.PRINCIPALES MEDIDAS DE RESULTADO:Opioide total prescrito, opioide total consumido, niveles de satisfacción del control del dolor y necesidad de prescripción adicional de opioides.RESULTADOS:Un total de 104 de 122 (85%) pacientes inscritos respondieron a la encuesta y se compararon con los 112 pacientes incluidos en el grupo de control. A pesar de una demografía similar, a la cohorte del estudio se le prescribió menos miligramos de equivalente de morfina (MME) (78,8 ± 11,3 frente a 294,0 ± 33,1, p <0,001), consumió menos MME (23,0 ± 28,0 frente a 57,1 ± 45,8, p <0,001) y presentaron una mayor tasa de uso de medicamentos no opioides (72% vs 10%, p <0,001). Los dos grupos tenían niveles similares de satisfacción del control del dolor (4,1 ± 1,3 frente a 3,9 ± 1,1 de 5, p = 0,12) y la necesidad de prescripción de opioides adicionales (5% frente a 4%, p = 1,0).LIMITACIONES:Experiencia en un solo centro con características específicas de la población de pacientes.CONCLUSIÓN:Las intervenciones educativas que enfatizan las cantidades recomendadas de prescripción de opioides basadas en la evidencia y los regímenes de dolor multimodales reglamentados son efectivas para disminuir la prescripción y el uso excesivos de opioides sin comprometer el control satisfactorio del dolor en pacientes sometidos a procedimientos anorrectales ambulatorios. Video Resumen en http://links.lww.com/DCR/B529.

HIT-It or Quit It: Heparin-Induced Thrombocytopenia Testing Appropriateness Using 4T Scoring and Inappropriate Testing Cost Analysis.

OBJECTIVES: The American Society of Hematology's 4T scoring system is a validated tool to assess a patient's probability of having heparin-induced thrombocytopenia (HIT) before testing is performed. There is no benefit to testing patients with a low probability 4T score for HIT. This study aimed to assess for inappropriate HIT testing at our institution based on 4T scoring. METHODS: We retrospectively reviewed 201 patient charts and calculated 4T scores and testing costs to assess for inappropriate testing and the economic impact of such testing. RESULTS: HIT testing often occurred in the least appropriate patients and resulted in tens of thousands of dollars of waste for unnecessary testing. CONCLUSIONS: Inappropriate testing for HIT is still a prevalent issue despite literature supporting the 4T score for guidance in testing appropriateness.

Posttreatment Lyme Disease Syndrome-What It Might Be and What It Is Not.

Lyme disease is a multisystem disease caused by Borrelia burgdorferi infection and accounts for well-defined manifestations, appearing either at an early or late stage. Appropriate antibiotic therapy generally leads to a favorable outcome. Still, unspecific persisting symptoms such as fatigue, myalgia, arthralgia or cognitive dysfunction are reported by several patients months to years after adequate treatment. Their underlying pathophysiologic mechanism is unclear. However, there is no evidence for microbiological persistence in these cases and attempts to resolve the symptoms by repeated or prolonged antibiotic treatment have not been convincingly successful, but they may rather be harmful. To narrow down the controversially handled entity of posttreatment Lyme disease syndrome (PTLDS) and to avoid overdiagnosis and overtreatment, case definitions have been proposed, acknowledging PTLDS as a complex of nonspecific, subjective symptoms, which are neither caused by ongoing infection nor by any other identifiable disease. PTLDS is mainly a diagnosis of exclusion and requires careful evaluation of differential diagnosis followed by counseling about optimal management in light of missing specific therapeutic options.

The Evolution of Our Understanding of the Biology of Cancer Is the Key to Avoiding Overdiagnosis and Overtreatment.

There has been a tremendous evolution in our thinking about cancer since the 1880s. Breast cancer is a particularly good example to evaluate the progress that has been made and the new challenges that have arisen due to screening that inadvertently identifies indolent lesions. The degree to which overdiagnosis is a problem depends on the reservoir of indolent disease, the disease heterogeneity, and the fraction of the tumors that have aggressive biology. Cancers span the spectrum of biological behavior, and population-wide screening increases the detection of tumors that may not cause harm within the patient's lifetime or may never metastasize or result in death. Our approach to early detection will be vastly improved if we understand, address, and adjust to tumor heterogeneity. In this article, we use breast cancer as a case study to demonstrate how the approach to biological characterization, diagnostics, and therapeutics can inform our approach to screening, early detection, and prevention. Overdiagnosis can be mitigated by developing diagnostics to identify indolent disease, incorporating biology and risk assessment in screening strategies, changing the pathology rules for tumor classification, and refining the way we classify precancerous lesions. The more the patterns of cancers can be seen across other cancers, the more it is clear that our approach should transcend organ of origin. This will be particularly helpful in advancing the field by changing both our terminology for what is cancer and also by helping us to learn how best to mitigate the risk of the most aggressive cancers.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."