Laboratory tests in primary care medicine: "essential laboratory tests" (1). Urinalysis

Japan Society of Clinical Pathology has formed a committee dealing with "lab. tests in primary care medicine". As the first step, they made "Essential Lab. Tests" which were composed of simple qualitative bed-side tests such as urinalysis, Complete blood count (CBC: Hb, Ht, WBC, RBC), CRP, or ESR (Erythrocyte sedimental rate), A/G ratio and biochemical tests if necessary (Table 1). We have performed "Essential Lab. Tests" on 1,026 outpatients who visited General Medicine Clinic for the first time. They consisted of 456 male (age 13-81), and 526 female (age 10-85). This report is the result of urinalysis from "Essential Lab. Tests" of 1,026 patients. 1) The result showed that overall positivity of the urinalysis was 21.3% (when more than one item of the qualitative tests was positive). 2) There was distinctive difference in the positivity of the urinalysis between the sex; i.e. protein and glucose were about twice frequently positive in male, where as occult blood and WBC (Esterase reaction) were 2-3 times more positive in female. 3) Urine protein shows positive in the individual 10-20 yrs old and more than 50 yrs old in both sexes. 4) Glucose was positive in over 40 yrs in male, and occult blood, 40-50 yrs or older in male. 5) WBC shows positive in all age groups in female and 50 yrs or older in male. 6) Positive WBC patients did not necessarily reflect urinary infection in female but nitrites roughly corresponded with urinary WBC in male of 50 yrs or older, meaning probable urinary infection associated with prostatic hypertrophy. 7) Abnormality of urinary sediment corresponded to the positive occult blood and WBC Erastase. 8) Urinalysis is an useful method of screening in primary care medicine.     

Usefulness of "essential laboratory tests" for the establishment of the initial diagnosis in new outpatients]

"Essential laboratory tests" advocated by Japan Society of Clinical Pathology were simultaneously performed with the history taking of the present illness and the physical examination in 1,026 new patients visited the outpatient unit of Comprehensive Medicine, National Defense Medical College. We have analyzed the usefulness of the "essential laboratory tests" for the establishment of the initial diagnosis in evaluable 750 patients by comparing the diagnosis made only by the history taking and the physical examination (tentative initial diagnosis) with that included the results of these laboratory tests. The "essential laboratory tests" had contributed to remarkably increased incidences of metabolic and endocrine diseases, liver or biliary tract diseases, renal and urinary tract diseases and anemia after the application of these tests. The initial diagnoses of 61 patients were successfully established by the addition of the "essential laboratory tests" among 157 cases of which tentative initial diagnoses remained undetermined. These tests confirmed the tentative diagnoses in 78 patients, while 78 tentative diagnoses were negated and corrected after evaluation of the results of these tests. Furthermore, the diagnostic tests such as CRP and leukocyte count were useful for the estimation of the nature or degree of seriousness of the disease in 57 patients. In addition, other diseases not related to the patient's chief complaint could be detected in 238 patients (303 total number of diseases) by these tests. These results indicate the usefulness of the "essential laboratory tests" not only for the establishment of more accurate initial diagnosis but also for the screening of the "hidden" diseases such as hyperlipidemia and liver dysfunction.     

"Essential laboratory tests" in primary care medicine--experiences in Comprehensive Medicine, National Defense Medical College]

The "essential laboratory tests" were applied to 1,026 new patients visiting the outpatient unit of Comprehensive Medicine, National Defense Medical College, to determine the usefulness of these tests in primary care medicine. The "essential laboratory tests" have contributed to the establishment of the initial diagnosis or confirmation of the "tentative initial diagnosis", and to the estimation of the nature or degree of seriousness of the disease. In addition, other diseases not related to the patient's chief complaint could be screened in 32% of the new patients examined with these tests. The "essential laboratory tests" were also found to be useful for the estimation of the presence of malignant tumors in 12 patients with various kinds of malignancies as well as the estimation or evaluation for such conditions as infection or inflammation, anemia, liver or renal dysfunction, and the ambulatory screening of metabolic diseases including hyperlipidemia, liver or urinary tract diseases. In conclusion, simultaneous performance of the "essential laboratory tests" with the history taking and the physical examination will provide important medical information in primary care medicine.     

A cost-effectiveness analysis of a pre-visit testing system for new outpatients in primary care medicine

We evaluated cost-effectiveness parameters of common diagnostic test panels advocated by the Japan Society of Clinical Pathology in order to determine the validity of pre-visit testing of these test panels for new outpatients with some defined symptoms. The "Essential Laboratory Tests(ELT) (2)" panel was universally applied to 540 new outpatients who visited the Comprehensive Medicine Clinics in the National Defense Medical College and its affiliated hospital. A "useful result(UR)", the unit of usefulness of the ELT, was assigned by assessing the impact of its results on physician's diagnosis- or decision-making. Patients were classified into 7 major symptom groups according to their chief complaint, and clinical effectiveness(UR/patient), economic efficiency(cost/UR) and cost-effectiveness(delta cost/delta UR) were analyzed in each patient group. Clinical effectiveness ranged from 1.38(renal/urinary tract symptoms) to 0.27 UR/patient(neurological symptoms) with a cost disparity from yen 1,222 to yen 5,946/UR between these patient groups. Substantial decreases in clinical effectiveness were demonstrated in all patient groups with the ELT(1)-testing alone in a simulation study; however, cost-effectiveness parameters still remain in excellent values in the renal/urinary tract symptom and infection/inflammation-related symptom groups(1.13 and 0.77 UR/patient at a cost of yen 836 and yen 1,181/UR, respectively). The addition of some ELT(2)-specific test items such as AST, ALT to the ELT(1) baseline panel improved clinical effectiveness of the ELT(1) in lassitude/exhaustive symptom group at a minimal cost increment. This study verified the validity of the ELT(1) as a panel for pre-visit testing in patients with renal/urinary tract symptoms and infection/inflammation-related symptoms, but not in those with other symptoms.     

The effectiveness of the essential laboratory tests in daily primary care--view of a physician at a private clinic]

I put into practice, "The essential laboratory tests (a proposal)" published by Japan Society of Clinical Pathology in 1989 on new patients who visited my clinic. It was useful not only for screening of diseases, but enhanced the probability of diagnosis. I could discover hidden abnormalities unrelated to the patient's complaints. Therefore, the condition of the patient could be judged theoretically and scientifically by the use of the essential laboratory tests.     

Entamoeba histolytica: efficacy of microscopic, cultural, and serological techniques for laboratory diagnosis.

Of 110 subjects with clinical evidence of amebiasis, 15 (14%) were shown to be infected with Entamoeba histolytica. Microscopic examination of stool specimens rendered a diagnosis in all eight cases of localized intestinal infection, but in only one of seven patients with invasive amebiasis. Culture was concomitantly diagnostic in six patients intestinal amebiasis and in one patient with extraintestinal infection. Assay for antibody to E. histolytica by counterimmunoelectrophoresis and indirect hemagglutination were each 100% effective in all cases of invasive amebiasis and in diagnosing two of eight patients with intestinal infection. Stool specimens of 15 patients revealing intestinal parasites other than E. histolytica failed to demonstrate cultural or serological evidence of amebiasis. Low levels of antibody were observed in the indirect hemagglutination assay in four patients with disease other than amebiasis and in three control sera positive for rheumatoid factor. By counterimmunoelectrophoresis, reactive sera were only encountered among those derived from patients with amebiasis. Six of seven patients with hepatic amebiasis may have gone undiagnosed if not for serology.     

Differential diagnosis of hepatitis: development of new laboratory tests for autoimmune hepatitis and progress in pathophysiology

Liver dysfunction has been found in 8.1% of postpartum women in the general population. This dysfunction was speculated to be developed by postpartum aggravation of subclinical autoimmune hepatitis. Therefore, we developed two methods for detection of autoantibodies to liver-specific antigens: an ELISA for anti-liver-specific arginase antibodies, and a highly sensitive radioligand assay for anti-CYP2D6 antibodies. Basic examinations of dilution curve, inhibition study and reproducibility were satisfactory for clinical application in both assays. Anti-arginase antibodies and anti-CYP2D6 antibodies were found in 28.6% and 42.6% of patients with autoimmune hepatitis, respectively. There was no correlation between the two autoantibodies and thus, combined use of these antibodies detects 55.3% of autoimmune hepatitis. Autoimmune hepatitis exists frequently when we include mild cases.     

Depression with atypical features in a sample of primary care outpatients: prevalence, specific characteristics and consequences

BACKGROUND: In the context of the current debate on the clinical relevance of atypical depression, the present study investigated the prevalence and specific characteristics of the disorder in depressed primary care outpatients and compared patients with atypical and with the prototypical form of depression ("non-atypical" depression). METHODS: 403 patients were examined using the Composite International Diagnostic Interview, Inventory of Depressive Symptomatology, Hamilton Depression Scale and DSM-IV criteria. Configurational frequency analyses (CFA) were conducted to identify non-random configurations of symptoms. Moreover, tests for independent sample comparisons were applied. RESULTS: The prevalence of atypical depression in our sample of depressed patients was 26.3%. CFA revealed one significant symptom pattern: mood reactivity without additional atypical features (p<0.000001). A significant difference emerged between patients suffering from atypical versus non-atypical depression in terms of severity (p< or =0.001). LIMITATIONS: The sample size was modest. CONCLUSIONS: A considerable proportion of depressed primary care outpatients may suffer from atypical depression which may contribute to under-recognition of depression in primary care. Results of CFA indicated the significance of mood reactivity which may also occur in depressed patients without additional atypical symptoms. Patients with atypical depression may suffer from less severe depression as compared to patients with non-atypical depression.     

Evaluation of enzyme-linked immunosorbent assays, an immunofluorescent-antibody test, and two rapid tests (immunochromatographic-dipstick and gel tests) for serological diagnosis of symptomatic and asymptomatic Leishmania infections in dogs

Enzyme-linked immunosorbent assays (ELISAs) based on soluble antigens derived from promastigote or amastigote-like stages of Leishmania infantum and on the recombinant rK39 antigen, each in combination with different conjugates [anti-immunoglobulin G1 [IgG1], anti-IgG2, anti-IgG(gamma), and anti-IgG heavy plus light chains], were compared to an immunofluorescent-antibody test (IFAT) and two commercially available rapid test systems (DiaMed-Vet-IT Leish and ID-PaGIA canine leishmaniasis antibody test) for the detection of specific anti-Leishmania antibodies in symptomatic and asymptomatic dogs with proven L. infantum infections. ELISAs based on soluble promastigote and amastigote antigens had very high sensitivities in symptomatic (n = 30; 100%) and asymptomatic dogs (n = 17; 94.1 to 100%), except when combined with the anti-IgG1 conjugate (41.2 to 82.4%). Specificities were high for all combinations (n = 50; 96 to 100%). The rK39 ELISA detected fewer asymptomatic cases (sensitivities, 52.9 to 64.7%) but was highly specific (96 to 100%). The IFAT was 90% sensitive in symptomatic dogs but was significantly less sensitive in asymptomatic cases (29.4%). However, it had an excellent specificity (100%). Test performances of the rapid tests based on the rK39 antigen were comparable to the ELISAs based on the same antigen. ELISAs based on soluble promastigote or amastigote antigens seem to be most suited for the serological diagnosis of canine Leishmania infections in both symptomatic and asymptomatic dogs. IFAT and the rK39 ELISA lack sensitivity in asymptomatic cases but are highly specific. Rapid tests like the rK39 dipstick test or the ID-PaGIA are helpful for confirming clinically suspected cases because of their high specificities in symptomatic animals.     

Laboratory diagnosis of Pneumocystis carinii: comparison of cytological, immunofluorescent and immunocytochemical staining]

Authors review several methods for diagnosis of Pneumocystis carinii on BAL fluid in AIDS patients aiming to identify ideal routine technic. Giemsa, Gomori and Toluidine Blue staining. Direct and Indirect Immunofluorescence. Immunocytochemical methods were tested and advantages/disadvantages compared on BAL fluid from AIDS patients. Pneumocystis carinii was detected in 7 out 21 cases (33%). Gomori staining and Toluidine Blue staining were chosen for routine Pneumocystis carinii detection while IF technics are deserved as very useful in fields showing high fungal ++ contamination (inducted sputum).     

Diabetes care from diagnosis: effects of training in patient-centred care on beliefs, attitudes and behaviour of primary care professionals

In a randomised trial, general practitioners and nurses in 21 practices were trained in patient-centred consulting and use of materials for people with Type 2 diabetes (GPs 0.5 days; nurses 1.5 days; two optional follow-up half-days). Twenty practices formed the comparison group. Professional beliefs, attitudes and behaviour were measured (pre-trial, close-of-course and end-of-trial), supported by patient reports of nurse behaviour (141 trained: 108 comparison patients, 1 year after diagnosis). A total of 49 practice nurses responded (29 trained; 20 comparison). Trained nurses rated relative importance of patient-centred to professional-centred care as greater than comparison nurses. Trained nurses became less keen on the approach during the trial, and perceived time constraints persisted. Patients diagnosed later in the study were less likely to recognise intervention materials. Trained nurses rated delivery of important aspects of care and satisfaction with style of care as lower than comparison nurses, but patients were more positive about delivery of care from trained than comparison nurses. Although nurses rated patient-centred care as important, whether or not they had been trained as part of the trial, the short, generalizable training programme significantly reduced nurse perceptions of their ability to deliver it. Nonetheless, patients reported that important aspects of diabetes care were delivered more if their nurses had been trained in patient-centred consulting. This raises issues concerning measurement scales completed by trained professionals.     

Canine sporotrichosis in Rio de Janeiro, Brazil: clinical presentation, laboratory diagnosis and therapeutic response in 44 cases (1998-2003).

A sporotichosis epidemic involving forty-four dogs in the Metropolitan area of Rio de Janeiro is described. Solitary skin lesions were noted in 18 dogs (40.9%), 2-4 such lesions were observed in 17 animals (38.6%), and nine (20.5%) animals had five or more lesions. Twenty-five (56.8%) animals had single ulcerated skin lesions on the nose and nine (20.5%) showed nasal mucosal involvement (three of which also has a skin lesion). Respiratory symptoms were observed in 17 (38.6%) dogs and were found to be the most common extracutaneous signs of infection. Anemia, leukocytosis with neutrophilia, hypoalbuminemia and hyperglobulinemia were the most frequent hematological abnormalities. Histopathological analysis of skin biopsies in most cases revealed granulomatous reactions characterized by histiocytic hyperplasia and neutrophil infiltration. Yeast-like cells were observed in seven (16.7%) of 42 dogs examined histologically. During the study, eight (18.2%) animals were lost to follow-up and three (6.8%) were submitted to euthanasia. Of the remaining 33 dogs, five (15.2%) presented spontaneous regression of the lesions, 26 (78.8%) were cured after treatment, and two (6%) continue to be treated. The present cases indicate that many dogs with sporotrichosis respond well to treatment and in a few dogs, the disease may be self-limiting.     

Comparable evaluation of serological diagnostic tests (ELISA, IFA and PA methods) for the detection of anti-Borrelia burgdorferi antibody]

We have evaluated the usefulness of the enzyme-linked immunosorbent assay (ELISA), indirect fluorescent antibody assay (IFA) and particle agglutination (PA) method as serological screening tests for Lyme-borreliosis. Serum samples obtained from two patients with Lyme-borreliosis showed marked high antibody titers for Borrelia burgdorferi when measured by these methods. Of the serum of 368 healthy members of the Self-Defense Force in north-eastern Japan screened for the antibody to B. burgdorferi, 8.4%, 3.7%, 4.6% were found positive by the ELISA, IFA, and PA method, respectively. However, Western blot analysis of these "positive" sera demonstrated no identical bands to those seen in the serum from the patients with Lyme-borreliosis. While 85% and 15% of Treponema pallidum hemagglutination test (TPHA)-positive sera (20 samples) showed a false-positive reaction by the ELISA and IFA method, respectively, no cross-reaction to the anti-B. burgdorferi antibody was observed in these sera by the PA method. The analysis of the serum of the patients with autoimmune diseases (rheumatoid arthritis; 11 cases, systemic lupus erythematosus; 46 cases) by the ELISA and PA methods resulted in a cross-reaction to some extent, which suggested that the antibodies produced by autoimmune mechanisms such as the anticardiolipin antibody can cause a cross-reaction to the anti-B. burgdorferi antibody. These findings indicate that the PA and ELISA rather than the IFA method should be recommended for rapid and conventional screening of Lyme-borreliosis and that serum "positive" for the anti-B. burgdorferi antibody determined by these tests should be confirmed by Western blot analysis to negate the cross-reactions.     

Sensitivity of enzyme-linked immunosorbent assay, complement fixation, and hemagglutination inhibition serological tests for detection of Sendai virus antibody in laboratory mice.

The enzyme-linked immunosorbent assay technique for detection of Sendai virus antibody in mice was approximately 100- and 300-fold more sensitive than the complement fixation and hemagglutination inhibition tests, respectively. The assay also permitted direct quantitative measurement of the amount of antibody on a single serum dilution rather than by the more traditional serial titration.     

Efficacy of several serological tests and antigens for diagnosis of bovine brucellosis in the presence of false-positive serological results due to Yersinia enterocolitica O:9

Yersinia enterocolitica O:9 bears a smooth lipopolysaccharide (S-LPS) of Brucella sp. O-chain A+C/Y epitopic structure and is a cause of false-positive serological reactions (FPSR) in standard tests for cattle brucellosis. Brucella S-LPS, cross-reacting S-LPSs representing several O-chain epitope combinations, Brucella core lipid A epitopes (rough LPS), Brucella abortus S-LPS-derived polysaccharide, native hapten polysaccharide, rough LPS group 3 outer membrane protein complexes, recombinant BP26, and cytosolic proteins were tested in enzyme-linked immunosorbent assays (ELISA) and precipitation tests to detect cattle brucellosis (sensitivity) and to differentiate it from FPSR (specificity). No single serological test and antigen combination showed 100% sensitivity and specificity simultaneously. Immunoprecipitation tests with native hapten polysaccharide, counterimmunoelectrophoresis with cytosolic proteins, and a chaotropic ELISA with Brucella S-LPS were 100% specific but less sensitive than the Rose Bengal test, complement fixation, and indirect ELISA with Brucella S-LPSs and native hapten or S-LPS-derived polysaccharides. A competitive ELISA with Brucella S-LPS and M84 C/Y-specific monoclonal antibody was not 100% specific and was less sensitive than other tests. ELISA with Brucella suis bv. 2 S-LPS (deficient in C epitopes), Escherichia hermannii S-LPSs [lacking the contiguous alpha-(1-2)-linked perosamine residues characteristic of Y. enterocolitica S-LPS], BP26 recombinant protein, and Brucella cytosolic fractions did not provide adequate sensitivity/specificity ratios. Although no serological test and antigen combination fully resolved the diagnosis of bovine brucellosis in the presence of FPSR, some are simple and practical alternatives to the brucellin skin test currently recommended for differential diagnosis.     

Reactivity of microhemagglutination, fluorescent treponemal antibody absorption, and venereal disease research laboratory tests in primary syphilis.

Seroreactivity in 130 cases of primary syphilis was 91.5% by fluorescent treponemal antibody absorption test, 82.3% by microhemagglutination (MHA-TP test), and 68.5% by the Venereal Disease Reseach Laboratory (VDRL) test. The MHA TP test generally became reactive earlier than the VDRL test and confirmed all reactive and most weakly reactive VDRL results.     

Attitudes toward integration of complementary and alternative medicine in primary care: perspectives of patients, physicians and complementary practitioners

OBJECTIVE: Our study explored the attitudes of patients toward complementary and alternative medicine (CAM) use, their family physicians' role regarding CAM, and models for CAM referral and treatment. We compared patients' perspectives regarding integration of CAM into primary care with attitudes of primary care physicians (PCPs) and CAM practitioners. METHODS: We conducted a comprehensive literature review and focus group discussions to develop a questionnaire, which we gave to three groups: a random sample of patients receiving care at an academic family medicine clinic and PCPs and CAM practitioners employed in the largest health maintenance organization in Israel. RESULTS: A total of 1150 patients, 333 PCPs, and 241 CAM practitioners responded to our questionnaire. Compared with PCPs, patients expected their family physician to refer them to CAM, to have updated knowledge about CAM, and to offer CAM treatment in the clinic based on appropriate training. When asked about CAM integration into medical care, more patients expected to receive CAM in a primary care setting compared to PCPs' expectations of prescribing CAM (62% vs. 30%; p=0.0001). Patients, CAM practitioners, and PCPs expected family practitioners to generate CAM referrals in an integrative primary care setting (85.6% vs. 82.4% vs. 62.6%; p<0.0001). Patients supported CAM practitioners providing CAM treatments in the primary care setting, regardless of whether the practitioner held a medical degree (MD). Also, more patients than PCPs or CAM practitioners expected their family physician to provide CAM (28.2% vs. 14.5% vs. 3.8%; p<0.0001). CONCLUSION: Patients, PCPs, and CAM practitioners suggested that family physicians play a central role in CAM referral and, to a lesser extent, that they actually provide CAM treatment themselves. PRACTICE IMPLICATIONS: PCPs need to be aware of their present and future role in informed referral to CAM and, to a lesser degree, in providing CAM in integrative primary care clinics. With the increasing use of CAM, patients may expect their family physician to be more knowledgeable, skillful, and have a balanced approach regarding CAM use. In addition, practitioners should learn how to communicate effectively and better collaborate with CAM practitioners to the benefit of their patients.