Antibody against Haemophilus influenzae protein D in patients with chronic conditions causing secondary immunodeficiency.

Prevalence of non-typeable Haemophilus influenzae (NTHi) in the etiology of invasive infections in immunocompromised individuals is increasing. Serum IgG antibody levels to H. influenzae protein D (PD) were significantly lower in adults suffering from chronic conditions causing secondary immunodeficiency (COPD, cancer, chronic renal failure, and diabetes) compared to age-matched healthy controls. A lack of naturally acquired antibody against this highly conserved antigen may contribute to an increased susceptibility to invasive NTHi disease. As COPD patients frequently infected with NTHi during disease exacerbations were unable to develop antibody response to PD, such defect could potentially contribute to the pathogenesis. Considering that pediatric PD-containing vaccines show protective effect against NTHi-caused otitis media, our data suggest the possibility of improving the defense against NTHi in COPD patients using immunization against PD. Although more research on the role of anti-PD antibody in protection against invasive NTHi disease is warranted, development of adult formulations of PD-based vaccines may be advantageous for prevention of severe infections in immunocompromised individuals.

Practising physician's knowledge and patterns of practice regarding the asplenic state: the need for improved education and a practical checklist.

OBJECTIVE: To examine physicians' knowledge and actions regarding the asplenic state and to develop a practical checklist to aid in the systematic education and management of asplenic patients. DESIGN: A prospective cohort survey utilizing an experienced nurse practitioner and a survey questionnaire with on-site interviews. SETTING: The Okanagan Valley, British Columbia. SUBJECTS: A cohort of 122 physicians serving a population base of 350,000. MAIN OUTCOME MEASURES: Beliefs and practices relating to vaccination and precautions necessary for adult and pediatric splenectomized patients. PRINCIPAL RESULTS: The majority of physicians appeared to be knowledgeable about potential conditions affecting splenic function, except in the case of severe liver disease with portal hypertension and collagen vascular disease. There appeared to be good understanding on the part of most physicians of the risks associated with various infectious diseases and the asplenic state, except in the case of Capnocytophaga canimorsus infection linked to dog bites and the increased susceptibility of asplenic patients to intraerythrocytic parasites. Although a majority of physicians were cognizant of the need for pneumococcal vaccination and other immunizations in adults, there was marked uncertainty in relation to the need and the appropriate time interval for revaccination. In the case of children there appeared to be uncertainty regarding the role of antibiotic prophylaxis. There were discrepancies between physicians' expressed attitudes and the actions actually taken for asplenic patients in individual practices. CONCLUSIONS: Further education is required concerning the management of asplenic patients. The systematic use of a practical checklist may facilitate this process.

Detection, education and management of the asplenic or hyposplenic patient.

Fulminant, potentially life-threatening infection is a major long-term risk after splenectomy or in persons who are functionally hyposplenic as a result of various systemic conditions. Most of these infections are caused by encapsulated organisms such as pneumococci, Haemophilus influenzae and meningococci. A splenectomized patient is also more susceptible to infections with intraerythrocytic organisms such as Babesia microti and those that seldom affect healthy people, such as Capnocytophaga canimorsus. Most patients who have lost their spleens because of trauma are aware of their asplenic condition, but some older patients do not know that they are asplenic. Other patients may have functional hyposplenism secondary to a variety of systemic diseases ranging from celiac disease to hemoglobinopathies. The identification of Howell-Jolly bodies on peripheral blood film is an important clue to the diagnosis of asplenia or hyposplenia. Management of patients with these conditions includes a combination of immunization, antibiotic prophylaxis and patient education. With the increasing prevalence of antibiotic-resistant pneumococci, appropriate use of the pneumococcal vaccine has become especially important.

Hematologic and oncologic emergencies. Doing the most good in the least time.

Broad categories of emergency hematologic and oncologic situations are metabolic crises, compressions and obstructions, and symptomatic cytopenias. In each instance, a decision to intervene should be made on the basis of findings on diagnostic assessment in combination with prognostic information. Management should be directly proportional to the possibility for cure, significant remission, or improved quality of life. Numerous diseases, including potentially curable cancer, can be modified and patients' quality of life substantially improved with appropriate emergency intervention. Fortunately, the modern therapeutic arsenal provides many specific measures to manage these challenging clinical situations.

Proportion positive for Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, Toxoplasma, and human immunodeficiency virus types 1 and 2 in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag.

OBJECTIVES: To determine the proportion of patients with evidence of an acute infection due to Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), Toxoplasma, or human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag, and to develop a cost-effective testing algorithm for managing such heterophile-negative patients. DESIGN: We conducted a prospective investigation of 70 selected outpatients who tested negative for heterophile antibody in association with an absolute lymphocytosis or instrument-generated atypical lymphocyte flag. The control population consisted of 50 patients who were heterophile negative and had a normal absolute lymphocyte count and no instrument-generated atypical lymphocyte flag. SETTING: A large outpatient laboratory system. INTERVENTION: Viral serology for HHV-6 was performed by immunofluorescence, and all other serologies were performed by enzyme-linked immunoassay. All testing was for immunoglobulin (Ig) M antibodies, except in the case of HIV. RESULTS: The proportion of study patients positive for EBV was 40% (28/70); for CMV, 39% (27/70); for HHV-6, 25% (16/65); for Toxoplasma, 3% (2/70); and for HIV, 0% (0/70). All 50 control patients were negative for EBV IgM antibodies. When patients with more than 1 positive viral test were excluded from analysis, positivity was 20% (9/45) for EBV, 22% (10/45) for CMV, 9% (4/45) for HHV-6, and 2% (1/45) for Toxoplasma. Utilizing hypothesis-generating logistic regression models, Downey type II atypical lymphocytes were significantly associated with EBV positivity (P =.006), while Downey type III lymphocytes were significantly associated with HHV-6 positivity (P =.016), and there was a trend for the association of Downey type I lymphocytes with CMV positivity (P =.097). CONCLUSIONS: A positive viral serology was identified in 70% of study patients. Multiple positive serologies complicate establishing a definitive diagnosis. Potential cost savings may be associated with the use of an appropriate testing algorithm.

A survey of aPTT reporting in Canadian medical laboratories. The need for increased standardization. Thrombosis Interest Group of Canada.

A survey of all licensed medical laboratories performing activated partial thromboplastin time (aPTT) testing in Canada was undertaken; the response rate was 50.7%. Preanalytic phase of testing seemed generally satisfactory, although 46% of laboratories were still using 3.8% or a 129-mmol/L concentration of citrate, and only 59% of institutions routinely performed testing to verify the platelet-poor status of the plasma used for aPTT testing. There were also concerns relating to the speed and duration of centrifugation for specimen preparation. While more than 67% of institutions had established an individual therapeutic range for aPTT testing, only 47% of laboratories verified this range with heparinized samples. Approximately 67% of the institutions that had verified the range had done this by spiking heparin concentrations into pooled plasma rather than using ex vivo specimens from patients receiving heparin therapy. There seemed to be a need for increased education about circumstances under which the therapeutic range should be rechecked and current standards for screening for the lupus anticoagulant. More than 71% of Canadian institutions surveyed used low-molecular-weight heparin, which may obviate many of the issues surrounding aPTT testing. Overall performance as documented by survey results seemed similar to that reported for the United States and Australasia.

Pneumococcal vaccine administration associated with splenectomy: the need for improved education, documentation, and the use of a practical checklist.

An audit was performed of the documentation of pneumococcal vaccination in splenectomy patients in three major hospitals involving a geographical population base of 350,000 patients in British Columbia, Canada. Overall, 111 of the 164 hospitalized splenectomy patients (68%) had received pneumococcal vaccination. Of elective splenectomy cases, only 11 of 55 (20%) had been vaccinated prior to surgery, as is currently recommended. One hundred fifty-five patients (95%) had splenectomy status mentioned in the discharge summary. However, only 35 (21%) had mention of vaccination status, 10 (6%) mention of the need for future revaccination, and only 8 (5%) notation of the possibility of future infectious risks. The rate of pneumococcal vaccination was as satisfactory as any reported in the literature to date. However, there is need for improved education in relation to the timing of vaccination and discharge summary documentation. A checklist for potential splenectomy patients may aid in improving this situation as may geographically based splenectomy registries.

Problems in interpreting laboratory tests. What do unexpected results mean?

It is always important that physicians not overreact to apparently abnormal laboratory values by undertaking inappropriate further investigations or clinical treatments. When confronted with unexpected differing test results from repeat testing in the same individual, physicians should be aware of explanations other than laboratory error and change in the patient's clinical status. While test-related variables may be factors, intraindividual biologic variation is much more common and may be the explanation for discrepant results. For this reason, physicians need to know which laboratory tests are associated with significant intraindividual biologic variation as well as the magnitude of possible changes. Age-associated physiologic changes may significantly alter certain laboratory values in the elderly without constituting a pathologic process. Laboratory values that may appear abnormal in 10% or more of the healthy elderly without necessarily representing a pathologic process include serum alkaline phosphatase, fasting blood glucose, 2-hour postprandial glucose, erythrocyte sedimentation rate, hemoglobin, and a normal serum creatinine level in the face of a markedly decreased creatinine clearance. To ensure proper assessment of the geriatic patient, the clinician needs to be aware of these age-related changes and possible effects on laboratory values. More clinical research is needed to establish appropriate reference ranges, especially for those over the age of 75 years.

Treating cancer patients. Practical monitoring and management of therapy-related complications.

OBJECTIVE: To review investigation and management of some common long-term complications associated with cancer chemotherapy and radiation therapy. QUALITY OF EVIDENCE: Databases searched using MeSH key words "cancer chemotherapy," "cancer chemotherapy complications," "radiation therapy," and "radiation therapy complications" included Ovid and CANCERLIT. Overall the literature in this area is not strong; treatment guidelines and consensus conferences generally are lacking. Recommendations in this paper are mainly based on the results of individual studies and case reports, as few randomized controlled trials have been performed. Where appropriate, recommendations incorporate results of published treatment guidelines and consensus conferences. MAIN MESSAGE: For most solid tumours, patients should be most frequently monitored during the first 3 years after completing initial treatment for cure. Follow-up monitoring usually incorporates physical examination as well as radiologic and laboratory investigations. Patients should not be lost to follow up once treatment is completed, but monitored regularly, especially while they are at highest risk for disease recurrence. Long-term complications associated with cancer therapy include postsplenectomy sepsis syndrome; central and peripheral nervous system toxicities; ocular complications; thyroid, pituitary, testicular, or ovarian dysfunction; pulmonary toxicity; vascular or lymphatic, gastrointestinal, or osseous complications; genitourinary problems; and possible secondary malignancy. CONCLUSION: Primary care physicians are key to facilitating appropriate follow up of treated cancer patients. To do this, they must be aware of practical aspects of monitoring and management of therapy-related complications.