A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours.

Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day(-1) of imatinib mesylate, 50 mg day(-1) of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day(-1) of imatinib had the highest MC (+/-s.d.) of treatment at $35,225.61 USD (+/-1253.65 USD); while sunitinib incurred a median MC of $17,805.87 USD (+/-694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (+/-472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients.

Frequency of macroprolactinemia due to autoantibodies against prolactin in pregnant women.

The frequency of macroprolactinemia related to the presence of anti-PRL autoantibodies in the serum of 209 healthy women at different stages of pregnancy was studied. Measurements were taken of serum PRL concentrations before and after chromatographic separation (gel filtration and affinity with proteins A and G) and extraction of free PRL with polyethylene glycol (PEG). Sera from 8 of the 209 women (3.8%) were found to have a significantly high proportion of precipitated PRL by PEG (macroprolactinemia); in these patients, gel filtration showed that a substantial amount of big big PRL (molecular mass >100 kDa) was present (19.0--78.2% vs. 3.8-4.9%, P = 0.009 in normal pregnant women with a normal proportion of precipitated PRL by PEG). The presence of macroprolactinemia was attributable to anti-PRL autoantibodies in 5 of the 8 women. Comparison of serum levels of direct and free PRL between women with macroprolactinemia related to anti-PRL autoantibodies and women without macroprolactinemia showed significant differences (direct PRL: 270.2 +/- 86.9 vs. 203.4 +/- 69.0 microg/L, P = 0.04; and free PRL: 107.0 +/- 75.9 vs. 173.3 +/- 67.6 microg/L, P = 0.002). On the other hand, there was no difference between women with macroprolactinemia not related to anti-PRL autoantibodies and women with macroprolactinemia caused by anti-PRL autoantibodies, nor was there a difference between women with macroprolactinemia not related to anti-PRL autoantibodies and women without macroprolactinemia. There was a positive correlation between titers of the anti-PRL autoantibody and serum PRL levels (r = 0.82, P = 0.09). The presence of the anti-PRL autoantibody had no relation to the patient's age, stage of gestation, or number of previous pregnancies. We concluded that the frequency of macroprolactinemia was 3.8% among healthy, pregnant women, which was caused by a anti-PRL autoantibodies in 62.5% of the cases. The autoantibodies were found in the bloodstream, forming a PRL-IgG complex, in accordance with the following observations: 1) immunoreactive PRL on gel filtration was eluted in the fractions corresponding to the molecular mass of IgG (150 kDa); 2) a significantly high proportion of immunoreactive PRL was retained on an affinity gel for IgG (proteins A and G); and 3) a significantly high proportion of serum PRL bound to IgG was precipitated by protein A. There was a positive correlation between titers of anti-PRL autoantibodies and serum PRL levels. Serum levels of total PRL were higher, and serum levels of free PRL were lower, in pregnant women with anti-PRL autoantibodies than in pregnant women without macroprolactinemia.

[Diagnostic yield of various urine tests in urinary tract infections]. / Rendimiento diagnóstico de algunas pruebas en orina en las infecciones de vías urinarias.

OBJECTIVES: 1. To determine the value of pyuria and bacteriuria by high-power field (hpf) in centrifuged urine and of tests with reactive strips for determining leukocyte estearase activity and nitrites in the diagnosis of urinary tract infection (UTI). 2. To establish the ideal cut-off point for these tests. DESIGN: Comparative survey. SETTING: Second level health care unit of the Instituto Mexicano del Seguro Social. PATIENTS AND METHODS: A total of 105 patients were prospectively studied, with or without urinary symptoms, seen in the emergency ward. MEASUREMENTS: A clinical history and physical exploration was done in each patient. A urine sample was used for microscopic analysis for determining leukocytes and bacteria using hpf microscopy; the urine leukocytes count was assayed as well as leukocyte estearase and nitrites using reactive strips. All samples were subjected to urine culture. Urine samples were obtained using a Nelaton probe in 65% of the patients and the rest using the midstream urination technique. RESULTS: Forty patients (38%) were identified as UTI cases based on clinical and laboratory criteria (urine culture and leukocyte count). The best cut-off point for number of leukocytes was 8 per hpf and for bacteriuria it was 2+ per hpf and for leukocyte estearase it was 1+. The sensitivity, specificity and predictive values of the pyuria hpf, bacteriuria by hpf and leukocyte estearase by reactive strip were comparable. The nitrites had a lower sensitivity than the other tests (p < 0.05). The negative predictive value of the nitrites was less than the microscopic bacteriuria (74% vs 85%, p = 0.005). The combination of positive tests in leukocytes and bacteriuria increased the specificity and the positive predictive value (99% and 96% respectively) when compared to the individual tests. CONCLUSIONS: The diagnostic performance of leukocyte estearase by reactive strips was similar to the microscopy of leukocytes and bacteria but the nitrite test had a lower performance. The combination of the leukocytes and bacteriuria measured by hpf appears to be very useful in the diagnosis of UTI.