These authors did not suggest clinical action be taken regarding these data, because the sample size was very small and likely unpowered. A thorough explanation of the procedure as well as risks, benefits, and alternative options should be provided to patients and families before the procedure. and E.L. were the cochairs of the panel and led the panel meetings. The certainty was categorized into 4 levels ranging from very low to high.12-14  Within this report, these categories are represented by the symbols, as follows: ⨁⨁⨁⨁ High certainty in the evidence about effects, ⨁⨁⨁◯ Moderate certainty in the evidence about effects, ⨁⨁◯◯ Low certainty in the evidence about effects, ⨁◯◯◯ Very low certainty in the evidence about effects, Interested readers may find more explanation about the GRADE approach to assessing and rating certainty in a body of evidence in other publications.12-14. Because of the paucity of direct evidence available in individuals living with SCD, the panel turned to indirect evidence to inform our recommendations. The guideline panel acknowledges that the systematic review did not identify data on all of the existing nonpharmacological therapies (eg, mindfulness, spirituality, exercise, and cognitive therapy) that may have the potential to reduce acute pain in SCD. The evidence for the effectiveness of opioids for pain relief as measured on a quantitative scale (VAS) compared with these other pharmacological treatments was mixed. Most of the evidence describing hospital-based acute care facilities places pain treatment in the context of complex SCD comprehensive care models. However, a tailored approach should be used that matches feasibility and acceptability for a given patient. The emergence of chronic pain occurs with increasing age, and it has been estimated that 30% to 40% of adolescents and adults living with SCD suffer from chronic pain.1,2  The management of acute and chronic SCD pain is a major clinical challenge. The panel acknowledges that these chronic nonopioid medications may not be accessible to all patients, potentially because of a lack of insurance coverage for some patients, which could have a negative impact on health equity. The ASH guideline panel suggests an individualized approach to initiating or discontinuing nonopioid therapy that is based on the balance between benefits and risks/harms and should consider functional outcomes and the durability of benefit over time. Opioid-related deaths in people without SCD reported in this study during the same timeframe was 174 959. The majority of patients would want the recommended course of action, but many would not. The hope is that these guidelines will provide structure around the management of acute and chronic SCD pain and identify areas of research needed that incorporate important patient-centered outcomes with the ultimate goal of decreasing pain-related suffering for individuals living with SCD. The panel discussed the fact that costs and resources can depend on the number of patients expected to use the SCD-specific acute care facility for pain management. For patients: a majority of individuals in this situation would want the suggested course of action, but many would not. However, all reviews cited insufficient methodological rigor of the trials included, and there were no studies of pediatric patients. Evidence for or against 4 therapeutic options was identified by the systematic review of evidence: NSAIDs, corticosteroids, subanesthetic ketamine, and regional anesthesia. A systematic review of pediatric and adult data and appraisal of the evidence were conducted to inform this question and recommendation. This recommendation was based on evidence from an RCT published after the NHLBI guidelines193  were released that assessed the efficacy of a personalized dosing protocol. The full-text version of this article contains a data supplement. Most members of the guideline panel were members of ASH. Initiation of therapy requires assessment and prediction of these risks and benefits and durability of benefit over time. Q9. It is good practice to deliver patient-centered education regarding the potential to develop chronic pain and the nonopioid pain treatment options that are outlined in recommendations 6, 7, and 8. Busse et al156  also compared the impact of COT and the same nonopioid pharmacological therapies on functional outcomes assessed with the 36-item Short Form Health Survey. The process for developing the guidelines, including updates and systematic review, was supported by the Mayo Evidence-Based Practice Research Program. No standardized, manualized universally accepted version of CBT is available for SCD in either adults or children. The potential benefits of using provider-delivered integrative pain management approaches in the context of a comprehensive disease pain management plan are low and include improved pain control, functioning,132  and HRQOL132  and reduced anxiety,139  frequency of pain episodes,132,139  and medication use.139  In other conditions, these provider-delivered integrative approaches are believed to have low risks and are helpful in combination with conventional treatments (ie, pharmacological and psychological). A systematic review of duloxetine for osteoarthritic pain: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? Therefore, all data reviewed were from published systematic reviews and meta-analyses conducted in another chronic noncancer pain population, those with fibromyalgia. These are clearly outlined in the remarks for recommendation 9b. Introduction-GRADE evidence profiles and summary of findings tables, GRADE: an emerging consensus on rating quality of evidence and strength of recommendations, Letters, numbers, symbols and words: how to communicate grades of evidence and recommendations, GRADE guidelines: 16. However, this report did not address the use of red blood cell transfusion for recurrent acute pain or chronic pain in children or adults with SCD.185  Therefore, the panel sought to systematically review the existing data and appraise the evidence to determine whether monthly transfusion should be used to prevent or reduce recurrent acute pain or chronic pain in this population. Time, financial costs, availability, training of therapists (ie, in chronic pain and SCD), and patient burden can be barriers to these types of psychological treatments that are being recommended. Particular attention was paid to the impact on patient-centered outcomes, including improved pain intensity, pain coping strategies, reduction in chronic opioid consumption (daily dose of MME), health care encounters (ED visits and hospitalizations), HRQOL, functional outcomes, sleep, mood, and patient and clinician global impression of change. The recommendations are labeled as either strong or conditional according to the GRADE approach. There was only speculative direct evidence supporting acupuncture use in adults with SCD and indirect evidence in adult mixed surgical populations on the benefits of acupuncture to reduce pain intensity. In children and adults who seek treatment of acute pain, should a standardized protocol be used that includes (1) reduced time to first dose (<1 h from arrival) in addition to more frequent reassessment and dosing of pain medication (<30 min) and (2) tailored dosing (vs weight-based dosing)? The lowest effective opioid dose should be prescribed. There were 7 systematic reviews identified in primarily mixed surgical populations using virtual reality,72-75  massage,76  and TENS.77,78  These reviews found significant improvements in pain intensity (massage, TENS, and VR) and significant reductions in opioid use (TENS) and length of stay (TENS). 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