Search Abstract The application of evidence-based medicine to the management of adults with sickle cell disease SCD is currently primarily driven by clinical expertise and patient preference, as there is a paucity of randomized controlled trial RCT data to guide decision-making. RCTs impacting current practices address use of hydroxyurea to prevent painful episodes and acute chest syndrome, intensity of pre-operative transfusion, transfusion during pregnancy, and angiotensin-converting enzyme inhibitor therapy for proteinuria, but most issues in adult SCD care have not been rigorously studied and management may not be appropriately extrapolated from pediatric data. While challenging clinical problems need to be addressed by RCTs, there is also the need for development of practice guidelines using formal methodological strategies. This brief review is not a substitute for the process but provides a literature-based approach to making treatment decisions when caring for adults with SCD. A major premise is that a hierarchy of evidence exists, with the well-designed randomized control trial RCT recognized as the strongest research design to evaluate treatment efficacy. The results of clinical trials involving pediatric patients with SCD influence the approach to the adult patient but there continues to be significant reliance on expert opinion to guide treatment of adults with SCD.
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Search Abstract The application of evidence-based medicine to the management of adults with sickle cell disease SCD is currently primarily driven by clinical expertise and patient preference, as there is a paucity of randomized controlled trial RCT data to guide decision-making. RCTs impacting current practices address use of hydroxyurea to prevent painful episodes and acute chest syndrome, intensity of pre-operative transfusion, transfusion during pregnancy, and angiotensin-converting enzyme inhibitor therapy for proteinuria, but most issues in adult SCD care have not been rigorously studied and management may not be appropriately extrapolated from pediatric data.
While challenging clinical problems need to be addressed by RCTs, there is also the need for development of practice guidelines using formal methodological strategies.
This brief review is not a substitute for the process but provides a literature-based approach to making treatment decisions when caring for adults with SCD. A major premise is that a hierarchy of evidence exists, with the well-designed randomized control trial RCT recognized as the strongest research design to evaluate treatment efficacy.
The results of clinical trials involving pediatric patients with SCD influence the approach to the adult patient but there continues to be significant reliance on expert opinion to guide treatment of adults with SCD.
The expanding adult SCD population places unique challenges on the health care delivery system. Since the majority of patients do not receive care through comprehensive sickle cell centers, the management of acute complications, surgery, and other interventions often involve physicians with limited experience in caring for the adult patient with SCD.
Thus, there is a clear need to provide clinical guidelines that are useful for a wide spectrum of health care providers. The following synthesis of information represents an initial step in the process. Pulmonary hypertension and hematopoietic cell transplantation will be covered elsewhere. An additional designation PED is provided to indicate if the evidence is based on studies limited to a pediatric population.
USPSTF level A strongly recommended and B recommended interventions should be routinely implemented, including screening for high blood pressure, lipid disorders, colorectal cancer, breast cancer, depression, primary prevention of cardiovascular events, and counseling for tobacco use.
The impact of SCD on screening criteria for intervention also needs to be considered. For example, persons with SCD have lower systolic and diastolic blood pressures as compared to matched controls. There are additional health maintenance concerns specific to patients with SCD.
Recommendations from the Advisory Committee on Immunization Practices for adults with SCD include immunization with the valent pneumococcal polysaccharide, Haemophilis influenzae type b, meningococcal and hepatitis B vaccines if not previously administered. Influenza vaccination on an annual basis and revaccination for pneumococcus one time after 5 years are also indicated Level III.
Transfusion Considerations Transfusion remains a mainstay in the management of SCD patients and will be discussed in the context of specific indications in subsequent sections. Simple transfusion can be used to improve dyspnea, severe fatigue or heart failure associated with an oxygen-carrying deficit or to decrease the percentage of Hb S containing cells.
Exchange techniques manual or automated erythrocytapheresis can be used to rapidly reduce the concentration of Hb S or when simple transfusion would result in hyperviscosity or volume overload. All patients should have complete RBC phenotyping performed prior to transfusion and antibody status should be reassessed 1—3 months after episodic transfusions Level III.
Chelation therapy is indicated for significant iron overload Level II Serum ferritin levels in SCD do not accurately reflect iron stores and quantitative tissue liver iron concentration may be needed to guide chelation therapy. Deferoxamine has been administered to SCD patients subcutaneously by continuous infusion, by twice daily subcutaneous injection, and intravenously.
Chronic erythrocytapheresis reduces iron accumulation Level II Treatment of Acute Painful Episodes Pain is the most common complication of SCD and frequent painful episodes are associated with increased mortality. This practice guideline addresses pain assessment, treatment of pain in various settings, and psychological, behavioral, and physical interventions. Other available treatment modalities have been examined in small-scale prospective studies.
A RCT of inhaled nitric oxide in 20 pediatric patients did not show a significant reduction in pain scores for the treatment group compared to placebo at the primary endpoint. Implementation of clinical pathways and standardized orders for hospital-based management of pain episodes based on APS algorithms and using multi-disciplinary approaches should be considered Level III.
Opioid medications are indicated for management of moderate to severe pain. The use of meperidine is not recommended Level III. Close monitoring of oxygen saturation and avoidance of excessive sedation are necessary Level III.
Oxygen supplementation is not indicated unless there is documented hypoxemia Level III. Intravenous fluids should be hypotonic and after correcting volume depletion, limited to 1—1. Blood transfusion is not indicated in the management of an uncomplicated pain episode 5 Level III. The administration of steroids is not recommended for an uncomplicated painful episode.
Acute pain management in a day hospital or an equivalent facility is effective in reducing hospital admissions Level II A 9-year follow-up observational study showed continuing benefit for patients taking HU. The effectiveness of HU therapy in patients with these genotypes has not been determined. Case series and reports indicate that repeated phlebotomy to lower the Hb level and induce iron deficiency can reduce the frequency of painful episodes in selected patients with high steady state Hb levels.
Non-pharmacologic approaches to management of chronic pain in adults with SCD have not been evaluated in controlled trials. Selected patients may benefit from non-pharmacologic therapies utilized in the management of other pain syndromes Level III. Chronic transfusion to suppress Hb S levels may be considered for the patient with debilitating refractory pain not responding to other interventions Level III.
Acute Chest Syndrome Acute chest syndrome ACS , the association of a new pulmonary infiltrate associated with acute respiratory symptoms, is a leading cause of mortality for adult patients.
A prospective multicenter study analyzed episodes of ACS in patients to determine the cause, clinical course and outcomes.
A standardized treatment protocol was used in that study see Table 5. There have been no controlled clinical trials addressing the use of inhaled bronchodilators, although a case-control study revealed an association of asthma and increased risk of developing ACS during a painful episode in children.
Secondary analysis of data from the STOP trial revealed a significant reduction in the frequency of ACS in the children on transfusion therapy compared to the control group.
Transfusion therapy is recommended if there is clinical deterioration, multilobar infiltrates, or a history of underlying pulmonary or cardiac disease Level III. There are no RCTs addressing the duration or intensity of chronic transfusion necessary to prevent recurrent strokes.
There were no recurrent ischemic events reported with a median follow-up of 7 years. The protocol was modified to assure overlap of HU to maximally tolerated doses prior to discontinuing transfusions, and the recurrence rate was 3.
There are no clinical trials addressing primary stroke prevention for patients with SCD over 16 years of age. Furthermore, there are no published studies addressing the treatment of acute ischemic stroke in adults with SCD, including the safety of recombinant tissue plasminogen activator or anti-platelet agents.
There are no clinical trials addressing the management of cerebral aneurysms in patients with SCD, but angiography is recommended in the evaluation of subarachnoid hemorrhage SAH due to the high incidence of multiple aneurysms. For adult patients who decide to discontinue transfusions, or those with problematic alloimmunization, iron overload, or other impediments to chronic red blood cell administration, HU therapy should be considered to prevent recurrent events although it has not been adequately studied Level III-PED.
There should be an overlap period to attain maximally tolerated doses and laboratory evidence of effect prior to discontinuing transfusions Level III-PED. The role of vascular bypass surgery in the management of moyamoya syndrome has not been addressed in a clinical trial and remains to be defined. The use of TCD is not recommended to screen adults to determine the risk of stroke.
The diagnostic testing for transient ischemic attack or stroke in adults with SCD should be the same as for those without a hemoglobinopathy Level III. The use of anti-platelet agents as prophylaxis following ischemic events has not been evaluated in SCD patients with stroke but may be considered if there are no contraindications Level III.
The role of chronic transfusion for the prevention of recurrent events has not been defined for patients with their initial stroke as an adult. Conventional angiography should be considered for patients with evidence of SAH to identify an arteriovenous malformation or aneurysm s amenable to surgery or other interventions Level III. Exchange transfusion prior to invasive angiography is recommended Level III. Preoperative Transfusion for Surgery Analysis of data from the Cooperative Study of Sickle Cell Disease demonstrated that administration of preoperative transfusions resulted in fewer complications in both adults and children.
There are no peer-reviewed published clinical trials comparing outcomes for preoperative transfusion to no transfusion. Approximately one-third of the procedures were associated with a complication. There were no significant differences between the treatment groups in the incidence of painful episodes, acute chest syndrome, or other complications. The applicability of these findings to older patients undergoing major procedures is uncertain.
The Study Group analyzed data for patients undergoing cholecystectomy including patients not enrolled in the RCT with 37 who did not receive transfusions. Management Principles Preoperative hydration, monitoring of oxygenation, and meticulous post-operative management including respiratory therapy are indicated for all patients undergoing general anesthesia Level III.
For the patient undergoing minor surgery not requiring general anesthesia preoperative transfusion is not routinely indicated Level III. As in other disease states, microalbuminuria and proteinuria may be indicative of early glomerular injury and renal dysfunction.
In small case series, administration of enalapril has been associated with normalized or markedly reduced albuminuria and proteinuria without changes in potassium excretion or significant changes in mean arterial blood pressure. Both hemodialysis and transplantation can be performed successfully. Steady-state hemoglobin values diminish with age, especially among patients older than 40 years. This progressive anemia may represent diminished renal function and erythropoietin production.
Management Principles Annual renal function should be assessed by measurement of serum creatinine and urinalysis for microalbuminuria or proteinuria Level III. Since fractional excretion of creatinine is increased, even mild elevation of serum creatinine may be indicative of renal insufficiency and warrants further investigation Level III. Patients with proteinuria should be treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker Level III.
Recombinant erythropoietin therapy for progressive anemia should be titrated as needed Level III. Renal replacement therapy, including dialysis and transplantation, should be pursued when indicated Level III. Case series indicate no detrimental effects. Contemporary data addressing pregnancy outcomes in women with SCD are predominately gathered from retrospective case series, 35 , 36 one prospective cohort study, 37 and one RCT of transfusion support. Adjusted analysis of the data was carried out by removing patients with previous perinatal mortality and multiple gestations.
Management of acute sickle cell complications, including pain, should be the same as for non-pregnant SCD patients, avoiding medications contraindicated during pregnancy Level III. Fetal monitoring should include periodic ultrasound to detect intrauterine growth retardation Level III.
Priapism Priapism in SCD is due to trapping of sickled cells in the corpora cavernosa. Stuttering priapism presents as recurring episodes lasting between 30 minutes and 4 hours whereas the prolonged form persists more than 4 hours and can result in corporeal fibrosis or impotence. Hydration, analgesics, and alkalinization of urine have been recommended to end an episode but have never been evaluated in clinical trials. For prolonged priapism, surgical intervention within 4 to 12 hours has been recommended to avoid sequelae.
Two case series reporting an association of neurological events with partial exchange transfusion and high end hemoglobin levels raise concerns about the use of aggressive transfusion for this indication.
Secondary prevention including the use of chronic transfusion has not been examined in rigorous clinical trials. There are case reports and series suggesting the utility of a variety of vaso-active agents. A crossover design clinical trial of stilbesterol demonstrated short term efficacy and there are case reports indicating benefit of gonadotropin releasing hormone agonists GnRH or anti-androgens. HU has been reported to prevent recurrences in 4 of 5 patients.
If conservative measures fail, aspiration of blood from the corpora cavernosa should be considered after 4 hours of symptoms Guidelines from the American Urological Association AUA www.
Management an evidence-based approach
Overview[ edit ] Evidence-based management entails managerial decisions and organizational practices informed by the best available evidence. The EBMgt website maintained at Stanford University provides a repository of syllabi, cases, and tools that can inform the teaching of evidence-based management. Efforts to promote EBMgt face greater challenges than have other evidence-based initiatives. In medicine there is more consensus as to what constitutes best evidence than in the social sciences more generally, and management in particular. Unlike medicine, nursing, education, and law enforcement, "Management" is not a profession. There are no established legal or cultural requirements regarding education or knowledge for an individual to become a manager. Managers have diverse disciplinary backgrounds.
Management: an evidence-based approach
With over 20 years of experience in organizational and applied psychology, Briner recalls seeing a lot of evidence-based practice and it struck him that it also applies to management and organizational behavior. Spreading his ideas through teaching, Briner explained that when he initially started in this field many managers defensively responded. Over time, he learned to pinpoint the issues at hand to help them figure out how to better fix the problems through evidence. Both Briner and Professor Walshe agreed that much of the management research that is published needs to be easily accessible so it can become more widely used. We are giving them really applicable strategies for managers to use. These students are not going to be academics, most of them.