Quality Improvement Intervention for Reduction of Redundant Testing.

Laboratory data are critical to analyzing and improving clinical quality. In the setting of residual use of creatine kinase M and B isoenzyme testing for myocardial infarction, we assessed disease outcomes of discordant creatine kinase M and B isoenzyme +/troponin I (-) test pairs in order to address anticipated clinician concerns about potential loss of case-finding sensitivity following proposed discontinuation of routine creatine kinase and creatine kinase M and B isoenzyme testing. Time-sequenced interventions were introduced. The main outcome was the percentage of cardiac marker studies performed within guidelines. Nonguideline orders dominated at baseline. Creatine kinase M and B isoenzyme testing in 7496 order sets failed to detect additional myocardial infarctions but was associated with 42 potentially preventable admissions/quarter. Interruptive computerized soft stops improved guideline compliance from 32.3% to 58% (P < .001) in services not receiving peer leader intervention and to >80% (P < .001) with peer leadership that featured dashboard feedback about test order performance. This successful experience was recapitulated in interrupted time series within 2 additional services within facility 1 and then in 2 external hospitals (including a critical access facility). Improvements have been sustained postintervention. Laboratory cost savings at the academic facility were estimated to be ≥US$635 000 per year. National collaborative data indicated that facility 1 improved its order patterns from fourth to first quartile compared to peer norms and imply that nonguideline orders persist elsewhere. This example illustrates how pathologists can provide leadership in assisting clinicians in changing laboratory ordering practices. We found that clinicians respond to local laboratory data about their own test performance and that evidence suggesting harm is more compelling to clinicians than evidence of cost savings. Our experience indicates that interventions done at an academic facility can be readily instituted by private practitioners at external facilities. The intervention data also supplement existing literature that electronic order interruptions are more successful when combined with modalities that rely on peer education combined with dashboard feedback about laboratory order performance. The findings may have implications for the role of the pathology laboratory in the ongoing pivot from quantity-based to value-based health care.

Hematologic Disorders: Anemia.

Anemia occurs in up to 25% of the US population. Normal hemoglobin levels vary by race, sex, and age. Classification of anemia by mean corpuscular volume guides the differential diagnosis and evaluation. Iron studies, reticulocyte count, the red blood cell distribution width index, and blood test results are used to make the diagnosis. Iron deficiency anemia is the most common microcytic anemia and is managed with iron therapy. Parenteral iron is available when the oral route cannot be used. Patients who do not benefit from therapy should be evaluated for adherence, malabsorption, occult bleeding, systemic disease, or less common inherited disorders. A source of gastrointestinal bleeding is found in 60% to 70% of patients with iron deficiency anemia who are referred for endoscopy. Normocytic anemia has a broad differential, including nutritional deficiencies, blood loss, renal disease, malignancy (solid tumors or hematologic cancer), rheumatologic disorders, endocrine disorders, and other systemic diseases. Macrocytic anemias are seen with vitamin B12 and folate deficiency, alcohol use, thyroid disease, hydroxyurea, antiretroviral drugs, myelodysplastic syndromes, and myeloma. Oral vitamin B12 is underused, and can be as effective as intramuscular vitamin B12 in managing anemia due to vitamin B12 deficiency.

Hematologic Disorders: Blood Transfusion Products.

Until the 1980s, liberal blood transfusion criteria with limited evidence were used regardless of the patient's clinical condition. However, blood transfusion products are associated with several risks, such as infection, acute lung injury, circulatory overload, and hemolytic transfusion reactions. More restrictive transfusion criteria and patient monitoring can decrease the need for transfusions, as well as decrease morbidity and mortality rates and costs. The national supply of blood products continues to decline with more stringent blood donor criteria. Preoperative autologous blood donation has fallen out of favor in patients without antibodies to high-incidence antigens because of increased rates of transfusion, waste of predonated units, and significant costs. Instead, preoperative erythropoietin plus iron therapy in patients who are at high risk of postoperative anemia as well as intraoperative techniques, such as use of antifibrinolytics and cell salvage, can prevent the need for allogeneic blood transfusion. Artificial blood products remain problematic and are not used in the United States.

Hematologic Disorders: Bone Marrow Failure.

Pancytopenia with hypocellular bone marrow most often is caused by idiopathic aplastic anemia, but can be caused by inherited bone marrow failure syndromes, drugs, infections, nutritional deficiencies, and rheumatologic disease. Aplastic anemia (AA) can remain stable for years but can become severe or transform into a myelodysplastic syndrome, acute leukemia, or paroxysmal nocturnal hemoglobinuria. Corticosteroids and erythropoietin are ineffective for management of aplastic anemia; and granulocyte colony-stimulating factor is only indicated in severe infections that do not improve with antibiotics. Supportive care with leukocyte-poor red blood cell transfusions reduces HLA antigen alloimmunization and platelet transfusion refractoriness. Horse or rabbit antithymocyte globulin plus cyclosporine typically is first-line therapy for patients with nonsevere AA who are transfusion-dependent, patients older than 40 years with severe AA, and patients with severe AA who lack an HLA antigen-matched sibling for bone marrow transplantation. The overall 5-year survival rate among patients taking antithymocyte globulin plus cyclosporine therapy is 75% to 85%. Bone marrow transplantation from an HLA antigen-matched sibling is considered the treatment of choice for severe AA in children and adults younger than 40 years. Less than approximately 33% of patients with AA have an HLA antigen-matched sibling donor, so matched unrelated donor hematopoietic stem cells are increasingly used. Umbilical cord stem cell transplantation is in clinical trials.

Hematologic Disorders: Sickle Cell Disease.

Sickle cell disease, the most common inherited hemoglobinopathy in the United States, is a group of autosomal recessive red cell disorders resulting from hemoglobin S. Hemoglobin S forms rigid polymers when deoxygenated that give red blood cells their sickle crescent shape. Increased viscosity and cell adhesion result in vasoocclusion. Universal screening of US newborns enables early detection. Prophylactic penicillin through age 5 years and pneumococcal immunization lower the risk of serious pneumococcal infections. Vasoocclusive crises are a major complication and cause severe pain; there is no objective confirmatory test. Intravenous hydration and rapid pain treatment with parenteral opioids are indicated for severe pain. Acute chest syndrome presents as a new pulmonary infiltrate with acute onset of symptoms of lower respiratory disease with or without fever. Stroke, acute ocular conditions, leg ulcers, priapism, and anemia are common complications of sickle cell disease. Hydroxyurea decreases sickling, improves red cell survival, and reduces the frequency of vasoocclusive crises. Hydroxyurea should be considered if three or more vasoocclusive crises occur per year. Multiple therapeutic transfusions are required, and the risks of iron overload and blood antibody development are high. Increased maternal-fetal risk occurs in pregnancy with sickle cell disease.

Glycemic control in hospitalized patients not in intensive care: beyond sliding-scale insulin.

Glycemic control in hospitalized patients who are not in intensive care remains unsatisfactory. Despite persistent expert recommendations urging its abandonment, the use of sliding-scale insulin remains pervasive in U.S. hospitals. Evidence for the effectiveness of sliding-scale insulin is lacking after more than 40 years of use. New physiologic subcutaneous insulin protocols use basal, nutritional, and correctional insulin. The initial total daily dose of subcutaneous insulin is calculated using a factor of 0.3 to 0.6 units per kg body weight, with one half given as long-acting insulin (the basal insulin dose), and the other one half divided daily over three meals as short-acting insulin doses (nutritional insulin doses). A correctional insulin dose provides a final insulin adjustment based on the preprandial glucose value. This correctional dose resembles a sliding scale, but is only a small fine-tuning of therapy, as opposed to traditional sliding-scale insulin alone. Insulin sensitivity, nutritional intake, and total daily dosing review can alter the physiologic insulin-dosing schedule. Prospective trials have demonstrated reductions in hyperglycemic measurements, hypoglycemia, and adjusted hospital length of stay when physiologic subcutaneous insulin protocols are used. Transitions in care require special considerations and attention to glycemic control medications. Changing the sliding-scale insulin culture requires a multidisciplinary effort to improve patient safety and outcomes.

Multiple myeloma: diagnosis and treatment.

Multiple myeloma, the most common bone malignancy, is occurring with increasing frequency in older persons. Typical symptoms are bone pain, malaise, anemia, renal insufficiency, and hypercalcemia. Incidental discovery on comprehensive laboratory panels is common. The disease is diagnosed with serum or urine protein electrophoresis or immunofixation and bone marrow aspirate analysis. Skeletal radiographs are important in staging multiple myeloma and revealing lytic lesions, vertebral compression fractures, and osteoporosis. Magnetic resonance imaging and positron emission tomography or computed tomography are emerging as useful tools in the evaluation of patients with myeloma; magnetic resonance imaging is preferred for evaluating acute spinal compression. Nuclear bone scans and dual energy x-ray absorptiometry have no role in the diagnosis and staging of myeloma. The differential diagnosis of monoclonal gammopathies includes monoclonal gammopathy of uncertain significance, smoldering (asymptomatic) and symptomatic multiple myeloma, amyloidosis, B-cell non-Hodgkin lymphoma, Waldenström macroglobulinemia, and rare plasma cell leukemia and heavy chain diseases. Patients with monoclonal gammopathy of uncertain significance or smoldering multiple myeloma should be followed closely, but not treated. Symptomatic multiple myeloma is treated with chemotherapy followed by autologous stem cell transplantation, if possible. Melphalan, prednisolone, dexamethasone, vincristine, doxorubicin, bortezomib, and thalidomide and its analogue lenalidomide have been used successfully. It is important that family physicians recognize and appropriately treat multiple myeloma complications. Bone pain is treated with opiates, bisphosphonates, radiotherapy, vertebroplasty, or kyphoplasty; nephrotoxic nonsteroidal anti-inflammatory drugs should be avoided. Hypercalcemia is treated with isotonic saline infusions, steroids, furosemide, or bisphosphonates. Because of susceptibility to infections, patients require broad-spectrum antibiotics for febrile illness and immunization against influenza, pneumococcus, and Haemophilus influenzae B. Five-year survival rates approach 33 percent, and the median survival rate is 33 months.