Meeting requirements of the California cholinesterase monitoring program

California (CA) has a long-standing formal blood cholinesterase (ChE) monitoring program for mixers, loaders, and applicators of pesticides. When the authors found commercial clinical kits were not optimal for assaying blood ChEs, CA regulations were revised to specify use of the Ellman ChE assay or to demonstrate a conversion factor with a correlation (r(2)) of 0.9 or better. The authors were enlisted to work with the clinical laboratories. Only two of seven participating laboratories generated an acceptable correlation for red blood cells (RBCs), whereas four of five laboratories had an acceptable correlation for plasma ChE. Subsequently, the CA Department of Pesticide Regulation (DPR) restated the need to meet this requirement and the authors worked with several of the clinical laboratories using a bovine ghost RBC ChE as a reference. Unfortunately, only 3 of 10 laboratories had acceptable correlations. Next, the authors provided all interested laboratories with human blood and plasma samples to perform the comparison study outlined in the regulation (Section 6728f). Fourteen laboratories participated; 9 met the ChE criteria for whole blood, 14 for plasma, and 6 for RBCs. Based on such data, on July 8, 2003, DPR notified the CA Agricultural Commissioners that nine of the participating laboratories were approved for ChE testing. Later work resulted in acceptable RBC values for two of the laboratories and their approval. The authors continue to work with laboratories interested in being on the approved list. The current list may be seen at www.cdpr.ca.gov/docs/whs/lablist.htm.     

Output congestion leads to compromised care in Peruvian public hospital neonatal units

Peru is moving toward a universal health insurance system, and it is facing important challenges in the provision of public health services. As more citizens gain access to health insurance, the flow of patients exceeds the capacity of public hospitals to provide care with quality. In this study we explore the relationship between technical efficiency and patient safety events in neonatal care units of Peru’s public hospitals. We use Data Envelope Analysis (DEA) with output congestion to assess the association between technical efficiency and patient safety events. We study 35 neonatal care units of public hospitals in Peru’s Social Security Health System, and identify two undesirable (risk-adjusted) safety outcomes: neonatal mortality and near-miss neonatal mortality. We found that for about half of hospital’s neonatal care units, technical efficiency is affected by output congestion. For those hospitals, patient safety is being compromised by receiving too many patients. Our results are consistent with public reports indicating that hospitals in the Peru’s Social Security Health System are overcrowded, affecting efficiency and jeopardizing quality of care. We found that most congested hospitals are located in the capital city and suburban areas, and are more likely to be hospitals with the lowest and the highest level of care. Our results call for improvements in the patient referral system and capacity expansion.     

<Emphasis Type="Italic">EGFR</Emphasis> Amplification and Sensitizing Mutations Correlate with Survival in Lung Adenocarcinoma Patients Treated with Erlotinib (MutP-CLICaP)

Background

Non-small cell lung cancer (NSCLC) has a 5-year survival of 5–16%. Epidermal growth factor receptor (EGFR) mutations, in most cases, confer sensitivity to EGFR tyrosine kinase inhibitor (TKI) therapy. Nonetheless, it is still unclear why clinical outcomes vary among patients with identical EGFR mutations. The amplification of the EGFR gene (EGFRamp) may play a significant role.

Objective

Compare the complete (CR) and partial response (PR) rates, overall survival (OS), and progression-free survival (PFS) in Hispanic patients with lung adenocarcinoma treated with erlotinib with EGFR mutations (L858R or exon 19 deletion [Del19]) with and without concomitant EGFRamp.

Patients and Methods

Seventy-two EGFR-positive lung adenocarcinoma patients of Hispanic origin, who underwent first-line treatment with erlotinib, were evaluated for EGFRamp by fluorescence in situ hybridization (FISH). The clinical outcomes were analyzed according to EGFR mutations and EGFRamp status.

Results

30.6% of samples showed EGFRamp, more frequently present in patients with Del19 (p?=?0.05). Patients with EGFRamp had a longer PFS (in months) [(28.5, 95% CI 22.3–34.6) vs. (11.0, 95% CI 8.2–16.7); p?=?0.002] and OS [(37.8, 95% CI 30.9–44.7) vs. (27.1, 95% CI 12.8–41.3); p?=?0.009] than those without. EGFRamp significantly influenced the response to erlotinib (p?=?0.0001). EGFRamp+/Del19 had a longer OS, 37.8 (95% CI 31.0–44.6), compared to EGFRamp+/L8585R, 27.5 (95% CI 12.4–42.5) (p?<?0.001) and longer PFS (p?=?0.043).

Conclusion

Among Hispanic patients, EGFRamp was present in 30% of patients with EGFR mutations. EGFR mutations and EGFRamp are associated with better OS, PFS, CR, and PR to erlotinib and, hence, could aid in the correct selection of patients that benefit from EGFR TKI treatment.

     

Administration of recombinant human granulocyte colony-stimulating factor to normal donors: results of the Spanish National Donor Registry. Spanish Group of Allo-PBT.

A Spanish National PBPC Donor Registry has recently been established for short- and long-term safety data collection in normal donors receiving rhG-CSF. To date, 466 donors have been included in the Registry. Median (range) dose and duration of rhG-CSF administration was 10 microg/kg/day (4-20) and 5 days (4-8), respectively. Donors underwent a median of two aphereses (range, 1-5). Adverse effects consisted mainly of bone pain (90.2%), headache (16.9%) and fever (6. 1%), but no donor discontinued rhG-CSF prematurely due to toxicity. Side-effects were more frequent in donors receiving >10 microg/kg/day than in those with lower doses (82.8% vs 61.8%; P = 0. 004). A significant decrease between baseline and post-apheresis platelet counts was the most important analytical finding (229 x 10(9)/l vs 140 x 10(9)/l; P < 0.0001), with a progressive reduction in platelet count with each apheresis procedure. One donor developed pneumothorax that required hospitalization due to central venous line placement. The mean CD34+ cell dose collected was 6.9 x 10(6)/kg (range, 1.3-36), with only 14 donors (2.9%) not achieving a minimum target of CD34+ cells of 2 x 10(6)/kg. No definitive information about potential long-term side effects is yet available. However, we hope this National Registry will serve as a useful basis for better monitoring of the efficiency and side-effects of cytokine administration in healthy people.     

The occurrence of adverse events during the infusion of autologous peripheral blood stem cells is related to the number of granulocytes in the leukapheresis product

Toxicity related to autologous PBSC infusion is well known and traditionally attributed to the presence of DMSO as cryoprotectant. But despite DMSO depletion, adverse events continue appearing. We have conducted a retrospective study to determine the incidence of adverse events related to the PBSC infusion in a large series of 144 patients. Adverse effects were observed in 67.36% of patients, although most of them were of grade 1 or 2. The adverse events most frequently reported were allergic reactions, followed by general, gastrointestinal and respiratory symptoms. In the univariate analysis, age (P=0.01), the volume infused (P=0.005), the amount of DMSO (P=0.008), the total nucleated cells (P=0.002), the total number of granulocytes (P=0.000001) and clumping (P=0.000001) were associated with the occurrence of adverse events. In the multivariate analysis, two protective factors, age (P=0.05) and sex (P=0.004), and two risk factors, the number of granulocytes, with a relative risk of 1.18 (95% confidence interval, 1.06-1.31) (P=0.002), and clumping, with an relative risk of 1.94 (95% confidence interval, 1.15-3.29) (P=0.013), were identified. The best cutoff point for the prediction of the occurrence of adverse events, with a sensitivity of 47% and specificity of 89%, was 6.065 x 10(9) granulocytes.     

Dialysis and transplant. Spain in 2005

In 2005, renal replace treatment (dialysis and transplant) was necessary for about 40,000 people, without being known the number accurate and either their basic characteristics, such as: time in treatment, modality or treatment changes. The presented data cover the 76% of the Spanish population and are the result of the cooperation among technicians of registries, nephrologists and transplant coordinations. 4,125 people started RRT in 2005, the total estimated acceptance rate for renal replacement therapy in adults in Spain was 126 pmp and regarding other European countries it locates us in an intermediate area. The incidence rate seems to keep stable in the last years although there were some differences among communities (from 104 pmp in Castile and Leon to 186 pmp in Canary Islands). Diabetes Mellitus is the most diagnosed cause of renal failure in 2005, more than 20% of patients, followed by vascular diseases. The estimated prevalence of renal replacement therapy in Spain at the end of 2005 was 903 pmp, with important variations among communities (from 806 pmp in Cantabria to 1056 pmp in Valencia Region). The 47% of prevalent RRT patients had a functioning transplant. Mortality on haemodialysis and peritoneal dialysis was 13.7% and 10.8% respectively. Mortality on transplant was 1.3%, one of the lowest values registered so far. Mortality on renal replacement therapy was around 5% among patients from 45 to 64 years, 11% between 65 and 74 years and 19% among the patients older than 75 years.