Citations

Abstract To provide direct comparison between apixaban and rivaroxaban in patients with acute cancer‐associated venous thromboembolism (Ca‐VTE), consecutive patients treated with apixaban, rivaroxaban, or enoxaparin at Mayo Thrombophilia Clinic (March 1, 2013 to January 31, 2018)) were followed prospectively. The primary effectiveness outcome was venous thromboembolism (VTE) recurrence, and the secondary was mortality. The primary safety outcome was major bleeding, the secondary clinically relevant safety outcome was non‐major bleeding (CRNMB), and the third a composite of major and CRNMB. There were 750 patients treated for acute Ca‐VTE with apixaban (n = 224), rivaroxaban (n = 163), and enoxaparin (n = 363) within 14 days of diagnosis and for at least 3 months, or until study event. Recurrent VTE was diagnosed in 11 receiving apixaban, 7 receiving rivaroxaban (apixaban vs rivaroxaban hazard ratio (HR) 1.31, 95% confidence interval (95% CI) 0.51‐3.36) and 17 in the enoxaparin receiving group (apixaban vs enoxaparin HR 1.14, 95% CI: 0.54, 2.42 and rivaroxaban vs enoxaparin HR 0.85, 95% Cl: 0.36, 2.06). There were 82 deaths in apixaban, 74 rivaroxaban (apixaban vs rivaroxaban HR 1.67, 95% Cl: 1.20, 2.33) and 171 in enoxaparin group (rivaroxaban vs enoxaparin HR 0.73, 95% Cl: 0.56, 0.96). Major bleeding occurred in 11 apixaban, 12 rivaroxaban (apixaban vs rivaroxaban HR 0.73, 95% Cl: 0.32, 1.66) and 21 enoxaparin group (apixaban vs enoxaparin HR 0.89, 95% Cl: 0.43, 1.84 and rivaroxaban vs enoxaparin HR 1.23, 95% Cl: 0.61, 2.50). The CRNMB rate was higher in rivaroxaban compared to apixaban ( P = .03) and LMWH ( P = .01) groups. Recurrence of VTE and major bleeding were similar in apixaban, rivaroxaban, and enoxaparin groups. Rivaroxaban was associated with higher CRNMB but lower mortality compared to apixaban and enoxaparin.

Objective Sudden hearing loss is a frightening symptom that often prompts an urgent or emergent visit to a health care provider. It is frequently, but not universally, accompanied by tinnitus and/or vertigo. Sudden sensorineural hearing loss affects 5 to 27 per 100,000 people annually, with about 66,000 new cases per year in the United States. This guideline update provides evidence‐based recommendations for the diagnosis, management, and follow‐up of patients who present with sudden hearing loss. It focuses on sudden sensorineural hearing loss in adult patients aged 18 and over and primarily on those with idiopathic sudden sensorineural hearing loss. Prompt recognition and management of sudden sensorineural hearing loss may improve hearing recovery and patient quality of life. The guideline update is intended for all clinicians who diagnose or manage adult patients who present with sudden hearing loss. Purpose The purpose of this guideline update is to provide clinicians with evidence‐based recommendations in evaluating patients with sudden hearing loss and sudden sensorineural hearing loss, with particular emphasis on managing idiopathic sudden sensorineural hearing loss. The guideline update group recognized that patients enter the health care system with sudden hearing loss as a nonspecific primary complaint. Therefore, the initial recommendations of this guideline update address distinguishing sensorineural hearing loss from conductive hearing loss at the time of presentation with hearing loss. They also clarify the need to identify rare, nonidiopathic sudden sensorineural hearing loss to help separate those patients from those with idiopathic sudden sensorineural hearing loss, who are the target population for the therapeutic interventions that make up the bulk of the guideline update. By focusing on opportunities for quality improvement, this guideline should improve diagnostic accuracy, facilitate prompt intervention, decrease variations in management, reduce unnecessary tests and imaging procedures, and improve hearing and rehabilitative outcomes for affected patients. Methods Consistent with the American Academy of Otolaryngology–Head and Neck Surgery Foundation’s Clinical Practice Guideline Development Manual, Third Edition , the guideline update group was convened with representation from the disciplines of otolaryngology–head and neck surgery, otology, neurotology, family medicine, audiology, emergency medicine, neurology, radiology, advanced practice nursing, and consumer advocacy. A systematic review of the literature was performed, and the prior clinical practice guideline on sudden hearing loss was reviewed in detail. Key action statements (KASs) were updated with new literature, and evidence profiles were brought up to the current standard. Research needs identified in the original clinical practice guideline and data addressing them were reviewed. Current research needs were identified and delineated. Results The guideline update group made strong recommendations for the following: clinicians should distinguish sensorineural hearing loss from conductive hearing loss when a patient first presents with sudden hearing loss (KAS 1); clinicians should educate patients with sudden sensorineural hearing loss about the natural history of the condition, the benefits and risks of medical interventions, and the limitations of existing evidence regarding efficacy (KAS 7); and clinicians should counsel patients with sudden sensorineural hearing loss who have residual hearing loss and/or tinnitus about the possible benefits of audiological rehabilitation and other supportive measures (KAS 13). These strong recommendations were modified from the initial clinical practice guideline for clarity and timing of intervention. The guideline update group made strong recommendation against the following: clinicians should not order routine computed tomography of the head in the initial evaluation of a patient with presumptive sudden sensorineural hearing loss (KAS 3); clinicians should not obtain routine laboratory tests in patients with sudden sensorineural hearing loss (KAS 5); and clinicians should not routinely prescribe antivirals, thrombolytics, vasodilators, or vasoactive substances to patients with sudden sensorineural hearing loss (KAS 11). The guideline update group made recommendations for the following: clinicians should assess patients with presumptive sudden sensorineural hearing loss through history and physical examination for bilateral sudden hearing loss, recurrent episodes of sudden hearing loss, and/or focal neurologic findings (KAS 2); in patients with sudden hearing loss, clinicians should obtain, or refer to a clinician who can obtain, audiometry as soon as possible (within 14 days of symptom onset) to confirm the diagnosis of sudden sensorineural hearing loss (KAS 4); clinicians should evaluate patients with sudden sensorineural hearing loss for retrocochlear pathology by obtaining a magnetic resonance imaging or auditory brainstem response (KAS 6); clinicians should offer, or refer to a clinician who can offer, intratympanic steroid therapy when patients have incomplete recovery from sudden sensorineural hearing loss 2 to 6 weeks after onset of symptoms (KAS 10); and clinicians should obtain follow‐up audiometric evaluation for patients with sudden sensorineural hearing loss at the conclusion of treatment and within 6 months of completion of treatment (KAS 12). These recommendations were clarified in terms of timing of intervention and audiometry, as well as method of retrocochlear workup. The guideline update group offered the following KASs as options: clinicians may offer corticosteroids as initial therapy to patients with sudden sensorineural hearing loss within 2 weeks of symptom onset (KAS 8); clinicians may offer, or refer to a clinician who can offer, hyperbaric oxygen therapy combined with steroid therapy within 2 weeks of onset of sudden sensorineural hearing loss (KAS 9a); and clinicians may offer, or refer to a clinician who can offer, hyperbaric oxygen therapy combined with steroid therapy as salvage therapy within 1 month of onset of sudden sensorineural hearing loss (KAS 9b). Differences from Prior Guideline Incorporation of new evidence profiles to include quality improvement opportunities, confidence in the evidence, and differences of opinion Included 10 clinical practice guidelines, 29 new systematic reviews, and 36 new randomized controlled trials Highlights the urgency of evaluation and initiation of treatment, if treatment is offered, by emphasizing the time from symptom occurrence Clarification of terminology by changing potentially unclear statements; use of the term sudden sensorineural hearing loss to mean idiopathic sudden sensorineural hearing loss to emphasize that over 90% of sudden sensorineural hearing loss is idiopathic sudden sensorineural hearing loss and to avoid confusion in nomenclature for the reader Changes to the key action statements (KASs) from the original guideline: KAS 1: When a patient first presents with sudden hearing loss, conductive hearing loss should be distinguished from sensorineural. KAS 2: The utility of history and physical examination when assessing for modifying factors is emphasized. KAS 3: The word routine is added to clarify that this statement addresses a nontargeted head computed tomography scan that is often ordered in the emergency room setting for patients presenting with sudden hearing loss. It does not refer to targeted scans such as a temporal bone computed tomography scan to assess for temporal bone pathology. KAS 4: The importance of audiometric confirmation of hearing status as soon as possible and within 14 days of symptom onset is emphasized. KAS 5: New studies were added to confirm the lack of benefit of nontargeted laboratory testing in sudden sensorineural hearing loss. KAS 6: Audiometric follow‐up is excluded as a reasonable workup for retrocochlear pathology. Magnetic resonance imaging, computed tomography scan if magnetic resonance imaging cannot be done, or, secondarily, auditory brainstem response evaluation are the modalities recommended. A time frame for such testing is not specified, nor is it specified which clinician should be ordering this workup; however, it is implied that it would be the general or subspecialty otolaryngologist. KAS 7: The importance of shared decision making is highlighted, and salient points are emphasized. KAS 8: The option for corticosteroid intervention within 2 weeks of symptom onset is emphasized. KAS 9: Changed to KAS 9a and 9b; hyperbaric oxygen therapy remains an option but only when combined with steroid therapy for either initial treatment (9a) or for salvage therapy (9b). The timing is within 2 weeks of onset for initial therapy and within 1 month of onset of sudden sensorineural hearing loss for salvage therapy. KAS 10: Intratympanic steroid therapy for salvage is recommended within 2 to 6 weeks following onset of sudden sensorineural hearing loss. The time to treatment is defined and emphasized. KAS 11: Antioxidants were removed from the list of interventions that the clinical practice guideline recommends against using. KAS 12: Follow‐up audiometry at conclusion of treatment and also within 6 months posttreatment is added. KAS 13: This statement on audiologic rehabilitation includes patients who have residual hearing loss and/or tinnitus who may benefit from treatment. Addition of an algorithm outlining KASs Enhanced emphasis on patient education and shared decision making with tools provided to assist in the same

Objective Sudden hearing loss is a frightening symptom that often prompts an urgent or emergent visit to a health care provider. It is frequently but not universally accompanied by tinnitus and/or vertigo. Sudden sensorineural hearing loss affects 5 to 27 per 100,000 people annually, with about 66,000 new cases per year in the United States. This guideline update provides evidence‐based recommendations for the diagnosis, management, and follow‐up of patients who present with sudden hearing loss. It focuses on sudden sensorineural hearing loss in adult patients aged ≥18 years and primarily on those with idiopathic sudden sensorineural hearing loss. Prompt recognition and management of sudden sensorineural hearing loss may improve hearing recovery and patient quality of life. The guideline update is intended for all clinicians who diagnose or manage adult patients who present with sudden hearing loss. Purpose The purpose of this guideline update is to provide clinicians with evidence‐based recommendations in evaluating patients with sudden hearing loss and sudden sensorineural hearing loss, with particular emphasis on managing idiopathic sudden sensorineural hearing loss. The guideline update group recognized that patients enter the health care system with sudden hearing loss as a nonspecific primary complaint. Therefore, the initial recommendations of this guideline update address distinguishing sensorineural hearing loss from conductive hearing loss at the time of presentation with hearing loss. They also clarify the need to identify rare, nonidiopathic sudden sensorineural hearing loss to help separate those patients from those with idiopathic sudden sensorineural hearing loss, who are the target population for the therapeutic interventions that make up the bulk of the guideline update. By focusing on opportunities for quality improvement, this guideline should improve diagnostic accuracy, facilitate prompt intervention, decrease variations in management, reduce unnecessary tests and imaging procedures, and improve hearing and rehabilitative outcomes for affected patients. Methods Consistent with the American Academy of Otolaryngology–Head and Neck Surgery Foundation's “Clinical Practice Guideline Development Manual, Third Edition” (Rosenfeld et al. Otolaryngol Head Neck Surg . 2013;148[1]:S1‐S55), the guideline update group was convened with representation from the disciplines of otolaryngology–head and neck surgery, otology, neurotology, family medicine, audiology, emergency medicine, neurology, radiology, advanced practice nursing, and consumer advocacy. A systematic review of the literature was performed, and the prior clinical practice guideline on sudden hearing loss was reviewed in detail. Key Action Statements (KASs) were updated with new literature, and evidence profiles were brought up to the current standard. Research needs identified in the original clinical practice guideline and data addressing them were reviewed. Current research needs were identified and delineated. Results The guideline update group made strong recommendations for the following: (KAS 1) Clinicians should distinguish sensorineural hearing loss from conductive hearing loss when a patient first presents with sudden hearing loss. (KAS 7) Clinicians should educate patients with sudden sensorineural hearing loss about the natural history of the condition, the benefits and risks of medical interventions, and the limitations of existing evidence regarding efficacy. (KAS 13) Clinicians should counsel patients with sudden sensorineural hearing loss who have residual hearing loss and/or tinnitus about the possible benefits of audiologic rehabilitation and other supportive measures. These strong recommendations were modified from the initial clinical practice guideline for clarity and timing of intervention. The guideline update group made strong recommendations against the following: (KAS 3) Clinicians should not order routine computed tomography of the head in the initial evaluation of a patient with presumptive sudden sensorineural hearing loss. (KAS 5) Clinicians should not obtain routine laboratory tests in patients with sudden sensorineural hearing loss. (KAS 11) Clinicians should not routinely prescribe antivirals, thrombolytics, vasodilators, or vasoactive substances to patients with sudden sensorineural hearing loss. The guideline update group made recommendations for the following: (KAS 2) Clinicians should assess patients with presumptive sudden sensorineural hearing loss through history and physical examination for bilateral sudden hearing loss, recurrent episodes of sudden hearing loss, and/or focal neurologic findings. (KAS 4) In patients with sudden hearing loss, clinicians should obtain, or refer to a clinician who can obtain, audiometry as soon as possible (within 14 days of symptom onset) to confirm the diagnosis of sudden sensorineural hearing loss. (KAS 6) Clinicians should evaluate patients with sudden sensorineural hearing loss for retrocochlear pathology by obtaining magnetic resonance imaging or auditory brainstem response. (KAS 10) Clinicians should offer, or refer to a clinician who can offer, intratympanic steroid therapy when patients have incomplete recovery from sudden sensorineural hearing loss 2 to 6 weeks after onset of symptoms. (KAS 12) Clinicians should obtain follow‐up audiometric evaluation for patients with sudden sensorineural hearing loss at the conclusion of treatment and within 6 months of completion of treatment. These recommendations were clarified in terms of timing of intervention and audiometry and method of retrocochlear workup. The guideline update group offered the following KASs as options : (KAS 8) Clinicians may offer corticosteroids as initial therapy to patients with sudden sensorineural hearing loss within 2 weeks of symptom onset. (KAS 9a) Clinicians may offer, or refer to a clinician who can offer, hyperbaric oxygen therapy combined with steroid therapy within 2 weeks of onset of sudden sensorineural hearing loss. (KAS 9b) Clinicians may offer, or refer to a clinician who can offer, hyperbaric oxygen therapy combined with steroid therapy as salvage therapy within 1 month of onset of sudden sensorineural hearing loss. Differences from Prior Guideline Incorporation of new evidence profiles to include quality improvement opportunities, confidence in the evidence, and differences of opinion Included 10 clinical practice guidelines, 29 new systematic reviews, and 36 new randomized controlled trials Highlights the urgency of evaluation and initiation of treatment, if treatment is offered, by emphasizing the time from symptom occurrence Clarification of terminology by changing potentially unclear statements; use of the term sudden sensorineural hearing loss to mean idiopathic sudden sensorineural hearing loss to emphasize that >90% of sudden sensorineural hearing loss is idiopathic sudden sensorineural hearing loss and to avoid confusion in nomenclature for the reader Changes to the KASs from the original guideline: KAS 1—When a patient first presents with sudden hearing loss, conductive hearing loss should be distinguished from sensorineural. KAS 2—The utility of history and physical examination when assessing for modifying factors is emphasized. KAS 3—The word “routine” is added to clarify that this statement addresses nontargeted head computerized tomography scan that is often ordered in the emergency room setting for patients presenting with sudden hearing loss. It does not refer to targeted scans, such as temporal bone computerized tomography scan, to assess for temporal bone pathology. KAS 4—The importance of audiometric confirmation of hearing status as soon as possible and within 14 days of symptom onset is emphasized. KAS 5—New studies were added to confirm the lack of benefit of nontargeted laboratory testing in sudden sensorineural hearing loss. KAS 6—Audiometric follow‐up is excluded as a reasonable workup for retrocochlear pathology. Magnetic resonance imaging, computerized tomography scan if magnetic resonance imaging cannot be done, and, secondarily, auditory brainstem response evaluation are the modalities recommended. A time frame for such testing is not specified, nor is it specified which clinician should be ordering this workup; however, it is implied that it would be the general or subspecialty otolaryngologist. KAS 7—The importance of shared decision making is highlighted, and salient points are emphasized. KAS 8—The option for corticosteroid intervention within 2 weeks of symptom onset is emphasized. KAS 9—Changed to KAS 9A and 9B. Hyperbaric oxygen therapy remains an option but only when combined with steroid therapy for either initial treatment (9A) or salvage therapy (9B). The timing of initial therapy is within 2 weeks of onset, and that of salvage therapy is within 1 month of onset of sudden sensorineural hearing loss. KAS 10—Intratympanic steroid therapy for salvage is recommended within 2 to 6 weeks following onset of sudden sensorineural hearing loss. The time to treatment is defined and emphasized. KAS 11—Antioxidants were removed from the list of interventions that the clinical practice guideline recommends against using. KAS 12—Follow‐up audiometry at conclusion of treatment and also within 6 months posttreatment is added. KAS 13—This statement on audiologic rehabilitation includes patients who have residual hearing loss and/or tinnitus who may benefit from treatment. Addition of an algorithm outlining KASs Enhanced emphasis on patient education and shared decision making with tools provided to assist in same

Abstract The diagnostic utility of somatic mutations in the context of cytopenias is unclear: clonal hematopoiesis can be found in healthy individuals, patients with aplastic anemia (AA), clonal cytopenia of undetermined significance (CCUS) and myelodysplastic syndrome (MDS). We examined a cohort of 207 well‐characterized cytopenic patients with a 640‐gene next generation sequencing (NGS) panel and compared its diagnostic utility with a “virtual” 41 gene panel. The TET2 , SF3B1 , ASXL1 , and TP53 were the most commonly mutated genes (frequency > 10%). Mutations in the 640‐gene panel show high sensitivity (98.3%) but low specificity (47.6%) for diagnosis of MDS. Notably, mutations of splicing factors and genes in the RAS pathway are relatively specific to MDS. Furthermore, high variant allele frequency (VAF) predicts MDS: when the VAF is set at 20%, the positive predictive value (PPV) for MDS is 95.9%, with a specificity of 95.3%. The presence of two or more somatic mutations with ≥10% VAF showed a PPV of 95.2%. While the “virtual” 41‐gene panel showed a mild decrease in sensitivity (95.7% vs 98.3%), 100% specificity was observed when either VAF was set at ≥20% (100% vs 95.3%), or two or more somatic mutations had VAFs ≥ 10%. Our study shows targeted gene panel sequencing improves the diagnostic approach and accuracy for unexplained cytopenia, with its high sensitivity and high PPV for MDS when applying VAF cutoffs. Furthermore, a 41‐gene panel was shown to have at least comparable performance characteristics to the large 640‐gene panel.

Cirrhotic cardiomyopathy (CCM) is cardiac dysfunction in patients with end‐stage liver disease in the absence of prior heart disease. First defined in 2005 during the World Congress of Gastroenterology, CCM criteria consisted of echocardiographic parameters to identify subclinical cardiac dysfunction in the absence of overt structural abnormalities. Significant advancements in cardiovascular imaging over the past 14 years, including the integration of myocardial deformation imaging into routine clinical practice to identify subclinical cardiovascular dysfunction, have rendered the 2005 CCM criteria obsolete. Therefore, new criteria based on contemporary cardiovascular imaging parameters are needed. In this guidance document, assembled by a group of multidisciplinary experts in the field, new core criteria based on contemporary cardiovascular imaging parameters are proposed for the assessment of CCM. This document provides a critical assessment of the diagnosis of CCM and ongoing assessment aimed at improving clinical outcomes, particularly surrounding liver transplantation. Key points and practice‐based recommendations for the diagnosis of CCM are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.

Objectives (1) To perform a systematic literature review to evaluate associations between post‐dural puncture headache (PDPH) and opening pressure (OP), closing pressure (CP), and volume of cerebrospinal fluid (V) removed. (2) To perform a case‐control study to evaluate pressure‐volume index (PVI) as a novel risk factor for PDPH. Background According to the International Classification of Headache Diagnoses, 3rd Edition (ICHD‐3), the diagnosis of PDPH requires documentation of intracranial hypotension. However, this remains an unproven concept. Methods A systematic literature review was conducted, searching Cochrane Database of Systematic Reviews, Ovid EMBASE, OVID MEDLINE, Scopus, and Web of Science. Study inclusion required a comparison of headache incidence following a LP as a function of OP, CP, and/or V. A retrospective, case‐control study with 1:1 matching was conducted utilizing ICHD‐3 criteria. Patients with factors that could influence CSF pressure were excluded. Results In our case‐control study, we did not identify a paired difference in either median (95% CI) elastance (0.05 [−0.09, 0.11], P = .503) or PVI (4.53 [−7.98, 19.97], P = .678). We identified 22 references, evaluating V (n = 14), OP (n = 11), and/or CP (n = 4). There was no convincing evidence for an association of PDPH with either OP or CP. A minority of studies documenting an association with V included patients with high‐volume CSF removal, and/or stratified patients by the timing of the headache onset. Conclusions The overall risk of PDPH does not appear to be influenced by OP, CP, V or PVI. PDPH may be related to V in instances of high‐volume removal, and depend on the timing of outcome assessment. Future revision of criteria should consider the existence of immediate and delayed PDPH subtypes, and not presume intracranial hypotension as a mandatory feature.

PURPOSE Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician’s choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer–specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor–negative patients (HR, 0.66; P = .02), but not among hormone receptor–positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor–negative disease. Competing risks in this older population dilute overall survival benefits.

AbstractNeuromuscular ultrasound has become an essential tool in the diagnostic evaluation of various neuromuscular disorders, and, as such, there is growing interest in neuromuscular ultrasound training. Effective training is critical in mastering this modality. Our aim was to develop consensus‐based guidelines for neuromuscular ultrasound training courses. A total of 18 experts participated. Expert opinion was sought through the Delphi method using 4 consecutive electronic surveys. A high degree of consensus was achieved with regard to the general structure of neuromuscular ultrasound training; the categorization of training into basic, intermediate, and advanced levels; the learning objectives; and the curriculum for each level. In this study, a group of neuromuscular ultrasound experts established consensus‐based guidelines for neuromuscular ultrasound training. These guidelines can be used in the development of the specialty and the standardization of neuromuscular ultrasound training courses and workshops.