The panel acknowledges that the evidence for use of these therapies in SCD is limited but also acknowledges that patients with SCD value nonpharmacological treatments that have few undesirable effects and can be used in conjunction with standard pharmacological treatments to reduce the burden of acute pain. A total of 54 adults with HbSS or HbSβ0 thalassemia had a minimum time of 6 months between at least 2 MRIs of the brain; in this group of adults, 43% (n = 23) had SCI at baseline and 57% (n = 31) had no SCI at baseline; individuals with overt stroke were excluded based on history and examination by a neurologist. Therefore, standardized self-reported assessments and outcomes are imperative. We did not have sufficient evidence to evaluate surgery in children and adults with SCD and moyamoya syndrome alone or moyamoya syndrome and silent cerebral infarcts. For adults and children with SCD who have chronic (as opposed to episodic) pain from the SCD-related identifiable cause of leg ulcers, the ASH guideline panel chooses not to offer a recommendation for or against any specific nonopioid pharmacological management strategy. Acute and chronic pain management for patients with SCD is addressed within existing evidence-based guidelines. Decision aids may be useful in helping individuals make decisions consistent with their individual risks, values, and preferences. Decision aids may be useful in helping patients make decisions consistent with their individual risks, values, and preferences. For each guideline question, the Mayo Center prepared a GRADE EtD framework, using the GRADEpro Guideline Development Tool (www.gradepro.org).16,21,22,31 The EtD table summarized the results of systematic reviews of the literature that were updated or performed for this guideline. We did not find a study describing the full range of challenges of regular blood transfusion therapy for families, but the panel, including the 2 patient representatives, believed strongly that family preferences and the inconvenience and financial resources associated with regular blood transfusion therapy should be considered. Decision aids may be useful in helping individuals make decisions consistent with their individual risks, values, and preferences. Part E summarizes ASH decisions about which interests were judged to be conflicts and how they were managed, including through recusal. In addition to site of care, variability exists around how opioids are delivered for treatment of acute pain both in the acute care setting (eg, ED and day hospital) and during hospitalization. The guideline panel determined that there is overall very low certainty in the evidence for a net benefit of provider-delivered integrative therapies, including massage and acupuncture, regarding patient-important outcomes associated with the treatment of chronic pain in patients with SCD. To obtain additional evidence that hydroxyurea decreases TCD measurements, the panel reviewed 10 studies in children with HbSS or HbSβ0 thalassemia who had TCD measurements at baseline and several months after starting hydroxyurea therapy (Figure 4). Currently, opioids constitute the mainstay of treatment of acute SCD pain when patients seek care in a health care setting. Because there was only 1 RCT and the other studies were observational, the recommendation was downgraded to conditional based on the low certainty in evidence. Table 3 provide GRADE’s interpretation of strong and conditional recommendations by patients, clinicians, health care policymakers, and researchers. Should cognitive rehabilitation therapy vs no rehabilitation be used for children and adults with SCD and cognitive deficit? The panel concluded that these interventions would probably not be acceptable to patients in the absence of data about true benefit. Celecoxib demonstrated a statistically significant reduction in total WOMAC score (MD , −4.41; 95% CI, −7.27 to −1.55), the WOMAC pain scale (MD, −0.86; 95% CI, −1.10 to −0.62), and the WOMAC function subscale (MD, −2.90; 95% CI, −5.12 to −0.67). Furthermore, these recommendations emphasize the individualized treatment approach (ie, not one size fits all) required for the management of chronic pain. There was also very limited direct evidence in individuals living with SCD upon which to base these recommendations. The Mayo Evidence-Based Practice Research Program conducted or updated systematic reviews based on clinical questions developed and defined by the ASH guideline panel. The indirect evidence base for leg ulcers largely was drawn from diabetic leg ulcers, and the literature was focused on wound healing outcomes rather than symptomatic treatment of pain. The EtD framework for each recommendation describes which individuals were recused from making judgments about each recommendation. Fewer adult studies were included, but small to large differences between the adults with SCD and controls were documented, with the greatest difference in processing speed.6, Vascular cognitive impairment is of particular concern in adults with SCD and requires ongoing efforts to identify cognitive symptoms and medical risk factors.128 Detection of cognitive impairments is important for identifying treatable causes, helping patients and families to understand the cause of functional deficits, and discussing the prognosis to plan for future needs.123 Outpatient services such as speech therapy, occupational therapy, or rehabilitation psychology may be indicated and available depending on the results of a full evaluation.129, In general, children and adults with SCD are a vulnerable population.
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