Cost-effectiveness of a workplace intervention for sick-listed employees with common mental disorders: design of a randomized controlled trial

Background  

Considering the high costs of sick leave and the consequences of sick leave for employees, an early return-to-work of employees with mental disorders is very important. Therefore, a workplace intervention is developed based on a successful return-to-work intervention for employees with low back pain. The objective of this paper is to present the design of a randomized controlled trial evaluating the cost-effectiveness of the workplace intervention compared with usual care for sick-listed employees with common mental disorders.     

Abnormal stimulated adherence of neonatal granulocytes: impaired induction of surface Mac-1 by chemotactic factors or secretagogues

To identify possible secretory determinants of impaired hyperadherence and stimulated migration of neonatal granulocytes (NGs), we performed correlative studies of: (a) specific granule content and exocytosis, (b) secretago-gue-mediated upregulation of f-met-leu-phe (fMLP) receptors, (c) the chemotactic induction of the adhesive glycoproteins Mac-1 alpha (complement receptor 3) and beta, and (d) morphometric assessments of specific (peroxidase negative) granule depletion following chemotactic stimulation. Lactoferrin (LF) content of NG suspensions (cord blood or peripheral blood cells) was profoundly diminished (mean +/- SD 51% +/- 18% of normal) as compared with healthy adult granulocytes (AGs). Despite diminished cellular content, LF release by NG suspensions in response to fMLP was comparable to that of AGs. In contrast, LF release by NG suspensions was significantly diminished in response to phorbol myristate acetate (PMA) or calcium ionophor A23187 and/or during stimulated cell spreading, experimental conditions promoting overall greater LF depletion than chemotactic stimuli. In addition, NGs demonstrated an impaired capacity to upregulate fMLP receptors in response to PMA or A23187 when tested under the same experimental conditions. Baseline expression of the adhesive glycoproteins Mac-1 alpha and beta on NG surfaces was normal, but induction or upregulation of these proteins by chemotactic concentrations of fMLP, C5a as well as secretory (high) concentrations of PMA and A23187, was significantly diminished as compared with AGs. In contrast, chemotactic induction of the surface expression of the complement receptor-1 (CR-1) on NGs was normal. An impaired induction of Mac-1 alpha or beta was directly related to an impaired enhancement of adherence of NG in response to fMLP over a chemotactically relevant concentration range (10(-10) to 10(-7) mol/L). Moreover, in blocking- incubation experiments using anti-Mac-1 alpha/beta monoclonal antibodies (MAbs), significantly less inhibition of adherence by these MAbs was evident with fMLP-stimulated NG as compared with AG suspensions. Under selected chemotactic conditions, ultrastructural assessments of NGs demonstrated diminished peroxidase-negative granule loss in association with diminished granule-membrane fusion and the "addition" of plasma membrane. These studies suggest that abnormal expression of multiple surface determinants derived from peroxidase- negative granules or other intracellular pools may contribute to deficient chemotaxis or other inflammatory functions of NGs.(ABSTRACT TRUNCATED AT 400 WORDS)     

Health care services utilization stratified by virological and immunological markers of HIV: evidence from a universal health care setting

Objective

The aim of the study was to determine rates of utilization of in‐patient, out‐patient and laboratory services stratified by virological and immunological markers of HIV disease among patients on antiretroviral treatment in British Columbia, Canada.

Methods

We estimated resource utilization for in‐patient visits, out‐patient visits, and laboratory tests among patients initiating antiretroviral treatment between 1 April 1994 and 31 December 2000, with follow‐up to 31 March 2001. Resource use was stratified by CD4 cell count and plasma HIV viral load (pVL) at the time of utilization and rates per 100 patient‐years were calculated for each health care resource.

Results

A total of 2718 patients were included in our analyses. The overall rates of in‐patient visits, out‐patient visits, and laboratory tests were 902, 3001 and 840 per 100 patient‐years, respectively. Utilization was higher for patients with low CD4 cell counts and high pVLs when compared with patients with high CD4 cell counts and low pVLs.

Conclusions

Patients with low CD4 cell counts and high pVLs had the highest use of health care services. Regular follow‐up with health care providers in an out‐patient setting, allowing for proper monitoring and maintenance of HIV care, is important in minimizing unnecessary and potentially costly in‐patient care.     

P-selectin mediates spontaneous leukocyte rolling in vivo

Rolling represents the initial step leading to leukocyte extravasation from blood vessels during an inflammatory reaction. In vitro studies indicate that P-selectin could be one of the ligands on endothelium involved in the rolling phenomenon, although the molecular determinants responsible for this transient attachment in vivo are still undefined. Our objectives were to develop a blocking monoclonal antibody against canine P-selectin and to use it to investigate the role of P-selectin in leukocyte rolling in vivo using the technique of intravital microscopy. P-selectin was immunoaffinity purified from canine platelets and used for the production of monoclonal antibodies. One of the hybridomas generated, MD6, was shown by enzyme-linked immunosorbent assay and by flow cytometry to bind preferentially to stimulated platelets and to completely prevent binding of stimulated platelets to neutrophils. Visualization of canine mesenteric venules by intravital microscopy showed that administration of MD6 resulted in a marked inhibition in the number of rolling leukocytes (18.96 +/- 9.92 v 156.40 +/- 19.50 leukocytes/min, P < .05; 88.3% +/- 6.0% inhibition). Control antibody MD3 (which recognizes a nonfunctional epitope of canine P- selectin) had no effect on the number of rolling leukocytes or on their rolling velocity. These results show for the first time that P-selectin plays an essential role in leukocyte rolling in vivo, and therefore may be a key participant of the inflammatory response.     

Analysis of a family of cyclin-dependent kinase inhibitors: p15/MTS2/INK4B, p16/MTS1/INK4A, and p18 genes in acute lymphoblastic leukemia of childhood

A newly recognized family of proteins that inhibit cyclin-dependent kinases (CDKs) termed cyclin-dependent kinase inhibitors (CDKI) have an important role in regulation of cell-cycle progression. A subfamily of these CDKIs (p15INK4B/MTS2, p16INK4/MTS1, and p18) have a high degree of structural and functional homology and are candidate tumor- suppressor genes. We evaluated the mutational status of the p15, p16, and p18 genes in 103 childhood acute lymphoblastic leukemia (ALL) samples and correlated these results with both their clinical data and additional results concerning their loss of heterozygosity in the region of the p15/p16 genes. Homozygous deletions of the p16 gene occurred extremely frequently in T-ALLs (17/22; 77%), and it was also frequent in precursor-B ALLs (12/81; 15%). Homozygous deletions of the p15 gene were also very frequent in T-ALLs (9/22; 41%), and it occurred in 5 of 81 (6%) precursor-B ALL samples. No deletions of p18 was found in any of the 103 ALL samples. Also, no point mutations of the p15, p16, and p18 genes were detected. We correlated p15/p16 alterations at diagnosis with their clinical characteristics as compared with 2,927 other patients treated similarly. Those with p15/p16 alterations were older; had higher white blood cell counts, often with T-cell ALL phenotype; and more frequently had a mediastinal mass at presentation; but they had the same nonremission, relapse, and survival rates at 5 years as did those patients whose blast cells did not have a p15/p16 deletion. To better understand the extent of alterations affecting chromosome 9p21 (location of the p15/p16 genes), loss of heterozygosity (LOH) was examined at D9S171, which is about 1 megabase proximal to the p15/p16 genes. LOH was detected in 15 of 37 (41%) informative samples. Interestingly, of the 24 informative samples that had no detectable alteration of the p15/p16 genes, 7 samples (29%) had LOH at D9S171. In summary, we show in a very large study that p15 and p16, but not p18, CDKI genes are very frequently altered in ALL; those with p15/p16 alterations are more frequently older children, have higher white blood cells at presentation, and often have a T-cell ALL phenotype. The LOH analysis suggests that another tumor-suppressor gene important in ALL also is present on chromosome 9p21.     

Evaluation of E-rosetting human lymphocytes with OKT11 and other monoclonal antibodies

Monoclonal antibody OKT11 was found to compete with sheep red blood cells for binding sites on human lymphocytes. Preincubation of lymphocytes with OKT11 eliminated E-rosette formation. In a study of 142 peripheral blood samples ranging from 1% to over 90% E-rosette- positive cells, comparison to the percent OKT11-positive cells yielded a correlation coefficient of 0.93. In normal donors, subsets of OKT11+ cells were identified using two-color immunofluorescent staining methods with OKT3, OKT4, and OKT8. On the average, approximately 13% of OKT11+ lymphocytes were OKT3- and 13% of OKT11+ lymphocytes were OKT4- and OKT8-. Based on our double antibody fluorescence intensity data, low antigen density OKT11+ lymphocytes were OKT3-. OKT4+ and OKT8+ lymphocytes in normal peripheral lymphocytes have similar OKT11 antigen density.     

Sl/Sld mouse bone marrow stroma in vitro contains an active radiation- sensitive inhibitor of normal hemopoiesis

Sl/Sld mice have a defective hemopoietic microenvironment. It has been assumed, based upon previous studies, that the primary abnormality in these mice is simply lack of a necessary supportive or inductive material within the hemopoietic stroma. We used in vitro long-term bone marrow cultures to characterize further the nature of the hemopoietic microenvironmental defect in Sl/Sld mice. Sl/Sld mouse bone marrow cells consistently produced less than 10% of the total hemopoietic cells and multipotent and unipotent hemopoietic progenitor cells produced in cultures of marrow from normal, congenic +/+ mice. If fresh Sl/Sld and +/+ marrow cells were mixed prior to establishing long-term marrow cultures, there was a direct correlation between number of Sl/Sld cells added and degree of inhibition of +/+ hemopoiesis. A pre- established, confluent Sl/Sld adherent stromal layer inhibited hemopoiesis by fresh +/+ marrow cells by nearly 70%, as compared with dishes with irradiated +/+ or no stroma. This inhibitory effect was abrogated by irradiation of the Sl/Sld stroma prior to addition of the fresh +/+ marrow cells. Similarly, unirradiated, but not 9 to 200 Gy irradiated Sl/Sld stroma inhibited proliferation of the factor- dependent FDC-P1 hemopoietic progenitor cell line. Thus, the Sl/Sld hemopoietic microenvironment actively inhibits hemopoiesis in vitro, and this inhibition can be at least partially eliminated by irradiation of the Sl/Sld stroma.