A systematic review supporting the Society for Vascular Surgery guidelines on the management of heritable aortopathies.

BACKGROUND: To support the development of clinical practice guidelines on the management of patients with genetic aortopathies and arteriopathies, a writing committee from the Society for Vascular Surgery has commissioned this systematic review. METHODS: We conducted a systematic review and searched multiple databases for studies addressing six questions identified by the Society for Vascular Surgery guideline committee about evaluating and managing patients with genetic aortopathies and arteriopathies. Studies were selected and appraised by pairs of independent reviewers. RESULTS: We included 12 studies in this systematic review. We did not identify studies about the long-term outcomes of endovascular repair for aortic aneurysm in patients with heritable aortopathy or about new aortic events in pregnant women with a history of aortic dissection (AD) or aneurysm. A small case series demonstrated a 100% survival rate and 100% aortic intervention-free survival at 15 months (range, 7-28 months) after endograft repair for type B AD. A positive genetic diagnosis was discovered in 36% of patients with aortic aneurysms and dissections who had no risk factors for hereditary aortopathies, and these patients had a mortality rate of 11% at a median follow-up duration of 5 months. Black patients had lower 30-day mortality than White patients (5.6% vs 9.0%, respectively), but they had a higher overall aortic reintervention rate at 30 days after AD repair (47% vs 27%, respectively). Aortic reinterventions owing to aneurysmal expansion and endoleak at 30 days were higher in Black patients than White patients. The certainty of evidence was judged to be very low across all the outcomes evaluated in this systematic review. CONCLUSIONS: The available evidence suggests high survival after thoracic endovascular aortic repair for type B AD in young patients with heritable aortopathies, but with limited long-term follow-up. Genetic testing in patients with acute aortic aneurysms and dissections had a high yield. It was positive for most patients with risk factors for hereditary aortopathies and in more than one-third for all other patients, and was associated with new aortic events within 15 years.

A systematic review supporting the Society for Vascular Surgery Guidelines on the management of carotid artery disease.

BACKGROUND: To support the development of guidelines on the management of carotid disease, a writing committee from the Society for Vascular Surgery has commissioned this systematic review. METHODS: We searched multiple data bases for studies addressing five questions: medical management vs carotid revascularization (CEA) in asymptomatic patients, CEA vs carotid artery stenting (CAS) in symptomatic low surgical risk patients, the optimal timing of revascularization after acute stroke, screening high-risk patients for carotid disease, and the optimal sequence of interventions in patients with combined coronary and carotid disease. Studies were selected and appraised by pairs of independent reviewers. Meta-analyses were performed when feasible. RESULTS: Medical management compared with carotid interventions in asymptomatic patients was associated with better early outcome during the first 30 days. However, CEA was associated with significantly lower long-term rate of stroke/death at 5 years. In symptomatic low-risk surgical patients, CEA was associated with a lower risk of stroke, but a significant increase in myocardial infarction compared with CAS during the first 30 days. When the long-term outcome of transfemoral CAS vs CEA in symptomatic patients were examined using preplanned pooled analysis of individual patient data from four randomized trials, the risk of death or stroke within 120 days of the index procedure was 5.5% for CEA and 8.7% for CAS, which lends support that, over the long term, CEA has a superior outcome compared with transfemoral CAS. When managing acute stroke, the comparison of CEA during the first 48 hours to that between day 2 and day 14 did not reveal a statistically significant difference on outcomes during the first 30 days. Registry data show good results with CEA performed in the first week, but not within the first 48 hours. A single risk factor, aside from peripheral artery disease, was associated with low carotid screening yield. Multiple risk factors greatly increase the yield of screening. Evidence on the timing of interventions in patients with combined carotid and coronary disease was sparse and imprecise. Patients without carotid symptoms, who had the carotid intervention first, compared with a combined carotid intervention and coronary artery bypass grafting, had better outcomes. CONCLUSIONS: This updated evidence summary supports the Society for Vascular Surgery clinical practice guidelines for commonly raised clinical scenarios. CEA was superior to medical therapy in the long-term prevention of stroke/death over medical therapy. CEA was also superior to transfemoral CAS in minimizing long-term stroke/death for symptomatic low risk surgical patients. CEA should optimally be performed between 2 and 14 days from the onset of acute stroke. Having multiple risk factors increases the value of carotid screening.

A Systematic Review Supporting the American Society for Dermatologic Surgery Guidelines on the Prevention and Treatment of Adverse Events of Injectable Fillers.

BACKGROUND: As the use of injectable skin fillers increase in popularity, an increase in the reported adverse events is expected. OBJECTIVE: This systematic review supports the development of American Society for Dermatologic Surgery practice guideline on the management of adverse events of skin fillers. METHODS AND MATERIALS: Several databases for studies on risk factors or treatments of injection-related visual compromise (IRVC), skin necrosis, inflammatory events, and nodules were searched. Meta-analysis was conducted when feasible. RESULTS: The review included 182 studies. However, IRVC was very rare (1-2/1,000,000 patients) but had poor prognosis with improvement in 19% of cases. Skin necrosis was more common (approximately 5/1,000) with better prognosis (up to 77% of cases showing improvement). Treatments of IRVC and skin necrosis primarily depend on hyaluronidase injections. Risk of skin necrosis, inflammatory events, and nodules may be lower with certain fillers, brands, injection techniques, and volume. Treatment of inflammatory events and nodules with antibiotics, corticosteroids, 5-FU, and hyaluronidase was associated with high response rate (75%-80%). Most of the studies were small and noncomparative, making the evidence certainty very low. CONCLUSION: Practitioners must have adequate knowledge of anatomy, elicit history of skin filler use, and establish preemptive protocols that prepare the clinical practice to manage complications.

Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-analysis.

Importance: Migraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy. Objective: To evaluate the benefits and harms associated with acute treatments for episodic migraine in adults. Data Sources: Multiple databases from database inception to February 24, 2021. Study Selection: Randomized clinical trials and systematic reviews that assessed effectiveness or harms of acute therapy for migraine attacks. Data Extraction and Synthesis: Independent reviewers selected studies and extracted data. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction or by using a fixed-effect model based on the Mantel-Haenszel method if the number of studies was small. Main Outcomes and Measures: The main outcomes included pain freedom, pain relief, sustained pain freedom, sustained pain relief, and adverse events. The strength of evidence (SOE) was graded with the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Findings: Evidence on triptans and nonsteroidal anti-inflammatory drugs was summarized from 15 systematic reviews. For other interventions, 115 randomized clinical trials with 28 803 patients were included. Compared with placebo, triptans and nonsteroidal anti-inflammatory drugs used individually were significantly associated with reduced pain at 2 hours and 1 day (moderate to high SOE) and increased risk of mild and transient adverse events. Compared with placebo, calcitonin gene-related peptide receptor antagonists (low to high SOE), lasmiditan (5-HT1F receptor agonist; high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (low SOE), butorphanol (low SOE), and tramadol in combination with acetaminophen (low SOE) were significantly associated with pain reduction and increase in mild adverse events. The findings for opioids were based on low or insufficient SOE. Several nonpharmacologic treatments were significantly associated with improved pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant difference in adverse events was found between nonpharmacologic treatments and sham. Conclusions and Relevance: There are several acute treatments for migraine, with varying strength of supporting evidence. Use of triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments was associated with improved pain and function. The evidence for many other interventions, including opioids, was limited.

A Systematic Review Supporting the Endocrine Society Guidelines: Management of Diabetes and High Risk of Hypoglycemia.

CONTEXT: Interventions targeting hypoglycemia in people with diabetes are important for improving quality of life and reducing morbidity and mortality. OBJECTIVE: To support development of the Endocrine Society Clinical Practice Guideline for management of individuals with diabetes at high risk for hypoglycemia. METHODS: We searched several databases for studies addressing 10 questions provided by a guideline panel from the Endocrine Society. Meta-analysis was conducted when feasible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess certainty of evidence. RESULTS: We included 149 studies reporting on 43 344 patients. Continuous glucose monitoring (CGM) reduced episodes of severe hypoglycemia in patients with type 1 diabetes (T1D) and reduced the proportion of patients with hypoglycemia (blood glucose [BG] levels <54 mg/dL). There were no data on use of real-time CGM with algorithm-driven insulin pumps vs multiple daily injections with BG testing in people with T1D. CGM in outpatients with type 2 diabetes taking insulin and/or sulfonylureas reduced time spent with BG levels under 70 mg/dL. Initiation of CGM in hospitalized patients at high risk for hypoglycemia reduced episodes of hypoglycemia with BG levels lower than 54 mg/dL and time spent under 54 mg/dL. The proportion of patients with hypoglycemia with BG levels lower than 70 mg/dL and lower than 54 mg/dL detected by CGM was significantly higher than point-of-care BG testing. We found no data evaluating continuation of personal CGM in the hospital. Use of an inpatient computerized glycemic management program utilizing electronic health record data was associated with fewer patients with and episodes of hypoglycemia with BG levels lower than 70 mg/dL and fewer patients with severe hypoglycemia compared with standard care. Long-acting basal insulin analogs were associated with less hypoglycemia. Rapid-acting insulin analogs were associated with reduced severe hypoglycemia, though there were more patients with mild to moderate hypoglycemia. Structured diabetes education programs reduced episodes of severe hypoglycemia and time below 54 mg/dL in outpatients taking insulin. Glucagon formulations not requiring reconstitution were associated with longer times to recovery from hypoglycemia, although the proportion of patients who recovered completely from hypoglycemia was not different between the 2 groups. CONCLUSION: This systematic review summarized the best available evidence about several interventions addressing hypoglycemia in people with diabetes. This evidence base will facilitate development of clinical practice guidelines by the Endocrine Society.

Perioperative Management of Vitamin K Antagonists and Direct Oral Anticoagulants: A Systematic Review and Meta-analysis.

BACKGROUND: The management of patients who are receiving chronic oral anticoagulation therapy and require an elective surgery or an invasive procedure is a common clinical scenario. RESEARCH QUESTION: What is the best available evidence to support the development of American College of Chest Physicians guidelines on the perioperative management of patients who are receiving long-term vitamin K agonist (VKA) or direct oral anticoagulant (DOAC) and require elective surgery or procedures? STUDY DESIGN AND METHODS: A literature search including multiple databases from database inception through July 16, 2020, was performed. Meta-analyses were conducted when appropriate. RESULTS: In patients receiving VKA (warfarin) undergoing elective noncardiac surgery, shorter (< 3 days) VKA interruption is associated with an increased risk of major bleeding. In patients who required VKA interruption, heparin bridging (mostly with low-molecular-weight heparin [LMWH]) was associated with a statistically significant increased risk of major bleed, representing a very low certainty of evidence (COE). Compared with DOAC interruption 1 to 4 days before surgery, continuing DOACs may be associated with higher risk of bleeding demonstrated in some, but not all studies. In patients who needed DOAC interruption, bridging with LMWH may be associated with a statistically significant increased risk of bleeding, representing a low COE. INTERPRETATION: The certainty in the evidence supporting the perioperative management of anticoagulants remains limited. No high-quality evidence exists to support the practice of heparin bridging during the interruption of VKA or DOAC therapy for an elective surgery or procedure, or for the practice of interrupting VKA therapy for minor procedures, including cardiac device implantation, or continuation of a DOAC vs short-term interruption of a DOAC in the perioperative period.

Perioperative Management of Antiplatelet Therapy: A Systematic Review and Meta-analysis.

Objective: To summarize the available evidence about the perioperative management of patients who are receiving long-term antiplatelet therapy and require elective surgery/procedures. Methods: This systematic review supports the development of the American College of Chest Physicians guideline on the perioperative management of antiplatelet therapy. A literature search of MEDLINE, EMBASE, Scopus and Cochrane databases was conducted from each database's inception to July 16, 2020. Meta-analyses were conducted when possible. Results: In patients receiving long-term antiplatelet therapy and undergoing elective noncardiac surgery, the available evidence did not show a significant difference in major bleeding between a shorter vs longer antiplatelet interruption, with low certainty of evidence (COE). Compared with patients who received placebo perioperatively, aspirin continuation was associated with increased risk of major bleeding (relative risk [RR], 1.31; 95% CI, 1.15-1.50; high COE) and lower risk of major thromboembolism (RR, 0.74; 95% CI, 0.58-0.94; moderate COE). During antiplatelet interruption, bridging with low-molecular-weight heparin was associated with increased risk of major bleeding compared with no bridging (RR, 1.86; 95% CI, 1.24-2.79; very low COE). Continuation of antiplatelets during minor dental and ophthalmologic procedures was not associated with a statistically significant difference in the risk of major bleeding (very low COE). Conclusion: This systematic review summarizes the current evidence about the perioperative management of antiplatelet therapy and highlights the urgent need for further research, particularly with the increasing prevalence of patients taking 1 or more antiplatelet agents.

A Systematic Review Supporting the Endocrine Society Clinical Practice Guideline for the Management of Hyperglycemia in Adults Hospitalized for Noncritical Illness or Undergoing Elective Surgical Procedures.

CONTEXT: Individuals with diabetes or newly recognized hyperglycemia account for over 30% of noncritically ill hospitalized patients. Management of hyperglycemia in these patients is challenging. OBJECTIVE: To support development of the Endocrine Society Clinical Practice Guideline for management of hyperglycemia in adults hospitalized for noncritical illness or undergoing elective surgical procedures. METHODS: We searched several databases for studies addressing 10 questions provided by a guideline panel from the Endocrine Society. Meta-analysis was conducted when feasible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess certainty of evidence. RESULTS: We included 94 studies reporting on 135 553 patients. Compared with capillary blood glucose, continuous glucose monitoring increased the number of patients identified with hypoglycemia and decreased mean daily blood glucose (BG) (very low certainty). Data on continuation of insulin pump therapy in hospitalized adults were sparse. In hospitalized patients receiving glucocorticoids, combination neutral protamine hagedorn (NPH) and basal-bolus insulin was associated with lower mean BG compared to basal-bolus insulin alone (very low certainty). Data on NPH insulin vs basal-bolus insulin in hospitalized adults receiving enteral nutrition were inconclusive. Inpatient diabetes education was associated with lower HbA1c at 3 and 6 months after discharge (moderate certainty) and reduced hospital readmissions (very low certainty). Preoperative HbA1c level < 7% was associated with shorter length of stay, lower postoperative BG and a lower number of neurological complications and infections, but a higher number of reoperations (very low certainty). Treatment with glucagon-like peptide-1 agonists or dipeptidyl peptidase-4 inhibitors in hospitalized patients with type 2 diabetes and mild hyperglycemia was associated with lower frequency of hypoglycemic events than insulin therapy (low certainty). Caloric oral fluids before surgery in adults with diabetes undergoing surgical procedures did not affect outcomes (very low certainty). Counting carbohydrates for prandial insulin dosing did not affect outcomes (very low certainty). Compared with scheduled insulin (basal-bolus or basal insulin + correctional insulin), correctional insulin was associated with higher mean daily BG and fewer hypoglycemic events (low certainty). CONCLUSION: The certainty of evidence supporting many hyperglycemia management decisions is low, emphasizing importance of shared decision-making and consideration of other decisional factors.

The Effectiveness and Safety of Platelet-Rich Plasma for Chronic Wounds: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness and adverse events of autologous platelet-rich plasma (PRP) in individuals with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers. PATIENTS AND METHODS: We searched multiple databases from database inception to June 11, 2020, for randomized controlled trials and observational studies that compared PRP to any other wound care without PRP in adults with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers. RESULTS: We included 20 randomized controlled trials and five observational studies. Compared with management without PRP, PRP therapy significantly increased complete wound closure in lower-extremity diabetic ulcers (relative risk, 1.20; 95% CI, 1.09 to 1.32, moderate strength of evidence [SOE]), shortened time to complete wound closure, and reduced wound area and depth (low SOE). No significant changes were found in terms of wound infection, amputation, wound recurrence, or hospitalization. In patients with lower-extremity venous ulcers or pressure ulcers, the SOE was insufficient to estimate an effect on critical outcomes, such as complete wound closure or time to complete wound closure. There was no statistically significant difference in adverse events. CONCLUSION: Autologous PRP may increase complete wound closure, shorten healing time, and reduce wound size in individuals with lower-extremity diabetic ulcers. The evidence is insufficient to estimate an effect on wound healing in individuals with lower-extremity venous ulcers or pressure ulcers. TRIAL REGISTRATION: PROSPERO Identifier: CRD42020172817.

Gastrointestinal motility evaluation in children with orthostatic intolerance: Mayo Clinic experience.

OBJECTIVE: Orthostatic intolerance (OI) and autonomic dysfunction (AD) are common in adolescents and young adults. Patients experience multisystem symptoms including gastrointestinal (GI), postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), or only symptoms of OI (SOI) without significant findings on 70-degree head-up tilt testing (HUT). We hypothesize that patients with POTS, OH, and SOI show differences in GI symptoms and motility test and that heart rate (HR) changes on HUT predict severity of GI dysmotility. STUDY DESIGN: From medical records of patients (<18 years) with OI, we collected demographics, presenting symptoms, GI manifestations, and GI motility testing. Data were compared between the 3 groups (POTS, OH, and SOI). We assessed changes in HR on HUT with changes on GI motility evaluation. RESULTS: Two hundred twenty-nine patients were included (73% females). Abdominal pain (65%), nausea (49%), vomiting (18%), and constipation (24%) were the most common GI symptoms. In patients who had motility evaluation, there were 27% (53/193) with delayed gastric emptying (GE) at 4 hours, 35% (32/92) with delayed colonic transit (CT), 55% (17/31) with reduced gastric accommodation (GA), and 75% (21/28) with dyssynergic defecation (DD). Among 100 POTS, 34 OH, and 95 SOI patients, no significant differences in GI symptoms or motility tests were identified and HR changes on HUT were not associated with changes on motility tests. CONCLUSION: GI symptoms are frequent in adolescents with OI and are associated with delayed GE, reduced GA, delayed CT, and presence of DD.

An Ophthalmic Insight into Novel Coronavirus 2019 Disease: A Comprehensive Review of the Ocular Manifestations and Clinical Hazards.

PURPOSE: To discuss the ocular manifestations provoked by novel coronavirus 2019 (COVID-19) disease in humans, the natural history of the disease in the eye, and its treatment. METHODS: We designed a narrative review of the ocular manifestations of COVID-19 based on the literature published till July 30, 2020. The databases were PubMed, Scopus, Cochrane Library, Google Scholar, and ScienceDirect. The inclusion criteria were (1) all types of clinical studies and (2) the topic was COVID-19 and its association to the eye regarding the current guidelines. RESULTS: From 168 abstracts screened, 61 papers fully filled the inclusion criteria after the full-text screening. The 61 records include 13 case reports, 17 prospective (case series or cross-sectional) studies, 8 retrospective studies, 12 literature reviews (one systematic review), and 11 letters to the editor. The majority of the papers agreed that ophthalmic manifestations due to COVID-19 were few and rarely encountered. The main ocular pathology seemed to be conjunctivitis, where the viral polymerase chain reaction also happened to be most detectable. Posterior segment or neuro-ophthalmic manifestations were scarce. Viral genome detection in the eye as well as viral portal of entry to the globe is still vague. CONCLUSION: The exact incidence of ocular manifestations in COVID-19 disease is uncertain. Conjunctivitis is the most prevalent ocular manifestation. It is still a debate whether the eye is a portal of entry for infection.

Targeted Therapy- and Chemotherapy-Associated Skin Toxicities: Systematic Review and Meta-Analysis.

PROBLEM IDENTIFICATION: Preventing and managing skin toxicities can minimize treatment disruptions and improve well-being. This systematic review aimed to evaluate the effectiveness of interventions for the prevention and management of cancer treatment-related skin toxicities. LITERATURE SEARCH: The authors systematically searched for comparative studies published before April 1, 2019. Study selection and appraisal were conducted by pairs of independent reviewers. DATA EVALUATION: The random-effects model was used to conduct meta-analysis when appropriate. SYNTHESIS: 39 studies (6,006 patients) were included; 16 of those provided data for meta-analysis. Prophylactic minocycline reduced the development of all-grade and grade 1 acneform rash in patients who received erlotinib. Prophylaxis with pyridoxine 400 mg in capecitabine-treated patients lowered the risk of grade 2 or 3 hand-foot syndrome. Several treatments for hand-foot skin reaction suggested benefit in heterogeneous studies. Scalp cooling significantly reduced the risk for severe hair loss or total alopecia associated with chemotherapy. IMPLICATIONS FOR RESEARCH: Certainty in the available evidence was limited for several interventions, suggesting the need for future research. SUPPLEMENTAL MATERIAL CAN BE FOUND AT&NBSP;HTTPS: //onf.ons.org/supplementary-material-targeted-therapy-and-chemotherapy-associated-skin-toxicity-systematic-review.

A Framework for Evidence Synthesis Programs to Respond to a Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic requires making rapid decisions based on sparse and rapidly changing evidence. Evidence synthesis programs conduct systematic reviews for guideline developers, health systems clinicians, and decision-makers that usually take an average 6 to 8 months to complete. We present a framework for evidence synthesis programs to respond to pandemics that has proven feasible and practical during the COVID-19 response in a large multistate health system employing more than 78,000 people. The framework includes four components: an approach for conducting rapid reviews, a repository of rapid reviews, a registry for all original studies about COVID-19, and twice-weekly prioritized update of new evidence sent to key stakeholders. As COVID-19 will not be our last pandemic, we share the details of this framework to allow replication in other institutions and re-implementation in future pandemics.