How to target disturbed identity in borderline patients? Self-identification program: A case study.

Borderline personality disorder (BPD) is a severe and relatively prevalent psychiatric disorder, responsible for high rates of suicidal behaviors. Disturbed identity appears as at the very core of this disorder, being inter-related with all other BPD features. Notably, from a dimensional perspective on mental disorders, one should realize that it is from our usual self-representation that we live all our daily experiences. Then, if the understanding of self-concept (or identity) is impaired, all the interventions implemented to decrease the self's suffering will subsequently be impaired. The purpose of the present case study was to illustrate the nine identity diffusion categories described by Jørgensen & Bøye (2022) and how the level of identity function can be improved in a third-wave cognitive and behavioral therapy targeting progressive correct self-identification.

Building a biopsychosocial model of cancer-related fatigue: the BIOCARE FActory cohort study protocol.

BACKGROUND: Cancer-related fatigue (CRF) is the most common side effect of cancer and cancer treatment. CRF prevalence is up to 50% in breast cancer patients and can continue several years after cancer remission. This persistent subjective sense of exhaustion is multifactorial. Numerous parameters have been evidenced to be related to CRF across biological, physical, psychological, social and/or behavioral dimensions. Although CRF has been studied for many years, the majority of previous studies focused on only one dimension, i.e., physical function. Moreover, few studies investigated CRF longitudinally with repeated measures. These are the two main obstacles that limit the understanding of CRF mechanisms. The purpose of this study is to create a biopsychosocial model of CRF with simultaneous and longitudinal anthropometric, clinical, biological, physical, psychological and sociological parameters. METHODS: BIOCARE FActory is a multicentric prospective study that will consist of an 18-month follow-up of 200 women diagnosed with breast cancer. Four visits will be scheduled at diagnosis, after treatments, and 12 and 18 months after diagnosis. The same procedure will be followed for each visit. Each session will be composed of anthropometric data collection, a semi-structured interview, cognitive tests, postural control tests, neuromuscular fatigability tests and a cardiorespiratory fitness test. Clinical and biological data will be collected during medical follow-ups. Participants will also complete questionnaires to assess psychological aspects and quality of life and wear an actigraphy device. Using a structural equation modeling analysis (SEM), collected data will build a biopsychosocial model of CRF, including the physiological, biological, psychological, behavioral and social dimensions of CRF. DISCUSSION: This study aims to highlight the dynamics of CRF and its correlates from diagnosis to post treatment. SEM analysis could examine some relations between potential mechanisms and CRF. Thus, the biopsychosocial model will contribute to a better understanding of CRF and its underlying mechanisms from diagnosis to the aftermaths of cancer and its treatments. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov ( NCT04391543 ), May 2020.

Fucoidan/VEGF-based surface modification of decellularized pulmonary heart valve improves the antithrombotic and re-endothelialization potential of bioprostheses.

Decellularized porcine heart valves offer promising potential as biocompatible prostheses. However, this procedure alter matrix fibres and glycans, leading to lower biomechanical resistance and increased their thrombotic potential. Therefore, their durability is limited due to calcification and weak regeneration in vivo. Surface modifications are highly requested to improve the scaffolds re-endothelialization required to restore functional and haemocompatible heart valve. Fucoidan, a natural sulphated polysaccharide, carries antithrombotic and anti-inflammatory properties and is known to enhance endothelial adhesion and proliferation when associated with vascular endothelial growth factor (VEGF). Based on these features, we constructed fucoidan/VEGF polyelectrolyte multilayer film (PEM) coated valve scaffold in an attempt to develop functional heart valve bioprosthesis. We investigated the haemocompatibility of the PEM coated valve scaffolds, the adhesion and growth potential of endothelial cells (HUVECs) in flow, as well as long term culture with stem cells. Fucoidan/VEGF PEM coated scaffolds demonstrated antithrombotic and non-calcifying properties. The PEM application increased HUVECs adhesion in flow (6 h) and HUVECs viability over time (72 h). HUVECs were well spread and aligned in flow direction. Interestingly, stem cells infiltration was improved by the PEM coating at 21 days. Thus, the fucoidan/VEGF PEM is a promising surface modification to obtain valve bioprostheses for clinical applications with increased antithrombotic and re-endothelialization potential.

Role of coagulation-associated processes on factor VIII immunogenicity in a mouse model of severe hemophilia A.

BACKGROUND: Immune responses to therapeutic factor VIII remain a major problem, affecting 30% of patients with severe hemophilia A. The primary factors that drive immune responses in these patients remain elusive. There have been conflicting reports on a role of coagulation (or thrombin) in anti-FVIII immune responses. OBJECTIVE: To assess the importance of coagulation-associated processes for the onset of the anti-FVIII immune response. METHODS: Using FVIII-deficient mice, we compared the immunogenicity of recombinant FVIII or the inactive FVIII(V) (634M) mutant. In parallel, the involvement of tissue factor (TF) activity in the anti-FVIII immune response was investigated upon injection of a neutralizing anti-TF antibody or by the use of chimeric mice that lack TF expression in myeloid cells. The development of the anti-FVIII immune response was also monitored after treatment with warfarin. RESULTS: The kinetics of the development of antibody responses to FVIII(V) (634M) were indistinguishable from those of wild-type FVIII. Inhibition of TF activity did not modulate immune responses to exogenous FVIII. Additionally, global inhibition of coagulation with warfarin failed to reduce the anti-FVIII immune response. CONCLUSIONS: Thrombin generation or coagulation-associated processes do not modulate the anti-FVIII antibody response in mouse model of severe hemophilia A.

Monocytes downregulate the early stage of collagen-induced platelet activation by a PECAM-1-dependent mechanism.

BACKGROUND: Blood vessel damage results in exposure of the subendothelial matrix, to which platelets adhere. Monocytes are recruited and activated at the site of injury. OBJECTIVES: Here we studied the effect of monocytes on platelet activation induced by exposure to fibrillar collagen. METHODS: Washed platelets and isolated monocytes (100/1) were coincubated with type I collagen in static adhesion conditions or in suspension. Platelet activation was assessed by measuring RANTES production and alpha-granule secretion. Platelet adherence on immobilized collagen was analyzed by fluorescence confocal microscopy. Cell-cell contacts were prevented by incubating platelets and monocytes in transwell coculture dishes. Experiments were also performed in the presence of soluble recombinant platelet endothelial cell adhesion molecule-1 (PECAM-1) or of antibodies to PECAM-1. RESULTS: Unexpectedly, unstimulated monocytes limited the initial phase of platelet activation by fibrillar collagen. In adhesion conditions, monocytes reduced the secretion by platelets of the inflammatory chemokine RANTES and of beta-thromboglobulin and the formation of platelet aggregates. The inhibitory effect of monocytes on platelet activation required direct cell-cell contacts between platelets and monocytes. Monocytes also inhibited collagen-induced platelet activation in suspension conditions as assessed by the reduction of P-selectin exposure and RANTES secretion. A recovery of platelet responses was observed in the presence of soluble PECAM-1 and of PECAM-1.3 Fab, indicating that PECAM-1 is involved in monocyte-triggered downregulation of platelet reactivity. CONCLUSIONS: Our data provide the first evidence that unstimulated monocytes limit the initial phase of platelet activation by collagen via a mechanism that is, at least in part, PECAM-1-dependent.

Interaction of rifalazil with oxidant-generating systems of human polymorphonuclear neutrophils.

It is well acknowledged that ansamycins display immunosuppressive and anti-inflammatory properties in vitro and in vivo. Rifalazil, a new ansamycin derivative, has not been studied in the context of inflammation. In particular, there are no data on the possible interference of rifalazil with oxidant production by phagocytes. We have compared the antioxidant properties of rifalazil to those of rifampin, a drug well known in this context, by using cellular and acellular oxidant-generating systems. Oxidant production by polymorphonuclear neutrophils was measured in terms of cytochrome c reduction, lucigenin-amplified chemiluminescence (Lu-ACL), and the 2',7'-dichlorofluorescin diacetate H2 (DCFDA-H2) technique (intracellular oxidant production). Rifalazil impaired O2- production in a concentration-dependent manner, with 50% inhibitory concentrations (IC50) (concentrations which inhibit 50% of the response) of 5.4 (30 and 60 min of incubation) and 6.4 (30 min) mg/liter, respectively, for phorbol myristate acetate (PMA) and formyl-methionyl-leucyl-phenylalanine (fMLP) stimulation. In agreement with the published fMLP-like activity of rifampin, the inhibitory effect of rifampin was significantly greater for fMLP (IC50 of 5.6 mg/liter) than for PMA (IC50 of 58 mg/liter) stimulation. Alteration of intracellular oxidant production was also observed with IC50 values similar to those obtained by the cytochrome assay. In addition, rifalazil and rifampin (> or = 25 mg/liter) scavenged O2-, as demonstrated by the acellular (hypoxanthine-xanthine oxidase) system. Interference with light detection systems was evidenced for both drugs by Lu-ACL. The clinical relevance of the antioxidant effect of rifalazil demonstrated in vitro, in particular its potential anti-inflammatory activity, requires further investigation.

Inflammatory, hemostatic, and clinical changes in a baboon experimental model for heatstroke.

The mortality and neurological morbidity in heatstroke have been attributed to the host's inflammatory and hemostatic responses to heat stress, suggesting that immunomodulation may improve outcome. We postulated that an experimental baboon model of heatstroke will reproduce human responses and clinical outcome to allow testing of new therapeutic strategies. Eight anesthetized juvenile baboons (Papio hamadryas) were subjected to heat stress in an incubator maintained at 44-47 degrees C until rectal temperature attained 42.5 degrees C (moderate heatstroke; n = 4) or systolic arterial pressure fell to <90 mmHg (severe heatstroke; n = 4) and were allowed to recover at room temperature. Four sham-heated animals served as a control group. Rectal temperature at the end of heat stress was 42.5 +/- 0.0 and 43.3 +/- 0.1 degrees C, respectively. All heat-stressed animals had systemic inflammation and activated coagulation, indicated by increased plasma IL-6, prothrombin time, activated partial thromboplastin time, and D-dimer levels, and decreased platelet count. Biochemical markers and/or histology evidenced cellular injury/dysfunction: plasma levels of thrombomodulin, creatinine, creatine kinase, lactic dehydrogenase, and alanine aminotransferase were increased, and varying degrees of tissue damage were present in liver, brain, and gut. No baboon with severe heatstroke survived. Neurological morbidity but no mortality was observed in baboons with moderate heatstroke. Nonsurvivors displayed significantly greater coagulopathy, inflammatory activity, and tissue injury than survivors. Sham-heated animals had an uneventful course. Heat stress elicited distinct patterns of inflammatory and hemostatic responses associated with outcome. The baboon model of heatstroke appears suitable for testing whether immunomodulation of the host's responses can improve outcome.

Polymorphisms of the tissue factor pathway inhibitor gene and the risk of restenosis after coronary angioplasty.

Intracoronary stent implantation is associated with a significantly lower risk of restenosis compared with balloon angioplasty. However, restenosis still occurs in some cases. Experimental studies suggest that the tissue factor pathway is involved in this phenomenon. We investigated a possible relationship between three previously identified polymorphisms of the tissue factor pathway inhibitor (TFPI) gene and restenosis in 443 patients who underwent angioplasty, with or without stent implantation. The effect of the intron 7-33T<--C polymorphism and that of the combined intron 7 and promoter genotype on plasma TFPI levels was also investigated in 58 healthy subjects. DNA analysis was performed by polymerase chain reaction amplification of genomic DNA extracted from white blood cells, followed by digestion with the restriction enzymes Hind III, Nde I and Mae III for the detection of promoter, intron 7 and exon IX polymorphisms, respectively. The minimal luminal diameter, percent stenosis, acute gain, late loss and loss index did not differ according to the genotype before, immediately after or 6 months after angioplasty, regardless of stent implantation. Interestingly, subjects with the intron 7 CC genotype had significantly higher total TFPI levels than those with the TT genotype before and after an enoxaparin injection. Moreover, subjects with the -287TT/Int7TT combined genotype had the lowest plasma TFPI levels. Despite significant variations in plasma TFPI levels, we found no evidence that three polymorphisms of the TFPI gene influence the risk of restenosis. These results do not exclude the possibility that other polymorphisms in the TFPI gene may influence this risk.

Tissue factor is not involved in the mitogenic activity of factor VIIa.

The present study was undertaken to evaluate in vitro the importance of tissue factor in the mitogenic effect of factor VIIa for embryonic fibroblasts. For that purpose, embryonic fibroblasts were isolated from either wild-type or transgenic mice showing a single inactivation of the tissue factor gene or expressing a truncated form (lacking the cytosolic domain) of this protein. Factor VIIa stimulated in a dose-dependent manner the growth of the 3 types of fibroblasts, thus showing that TF is not involved in the mitogenic activity of factor VIIa. The mitogenic activity of factor VIIa disappeared in serum immunopurified in factor X and was almost totally inhibited by DX9065, a selective factor Xa inhibitor, showing that this effect of factor VIIa occurred via factor Xa generated during the incubation period. Hirudin did not show any significant effect on factor VIIa-induced fibroblast proliferation, thus showing that the effect observed for factor VIIa was selectively mediated by factor Xa and was not due to thrombin formation. Our results therefore represent the first evidence for the possible importance of factor Xa in the mitogenic effect of factor VIIa and show the negligible role of tissue factor in this process.

Vascular endothelial growth factor production by fibroblasts in response to factor VIIa binding to tissue factor involves thrombin and factor Xa.

Tissue factor (TF) assembled with activated factor VII (FVIIa) initiates the coagulation cascade. We recently showed that TF was essential for FVIIa-induced vascular endothelial growth factor (VEGF) production by human fibroblasts. We investigated whether this production resulted from TF activation by its binding to FVIIa or from the production of clotting factors activated downstream. Incubation of fibroblasts with a plasma-derived FVIIa concentrate induced the generation of activated factor X (FXa) and thrombin and the secretion of VEGF, which was inhibited by hirudin and FXa inhibitors. By contrast, the addition of recombinant FVIIa to fibroblasts did not induce VEGF secretion unless factor X was present. Moreover, thrombin and FXa induced VEGF secretion and VEGF mRNA accumulation, which were blocked by hirudin and FXa inhibitors, respectively. The effect of thrombin was mediated by its specific receptor, protease-activated receptor-1; in contrast, the effect of FXa did not appear to involve effector cell protease receptor-1, because it was not affected by an anti-effector cell protease receptor-1 antibody. An increase in intracellular calcium with the calcium ionophore A23187 or intracellular calcium chelation by BAPTA-AM had no effect on either basal or FXa-induced VEGF secretion, suggesting that the calcium signaling pathway was not sufficient to induce VEGF secretion. Finally, FVIIa, by itself, had no effect on mitogen-activated protein (MAP) kinase activation, contrary to thrombin and FXa, which activate the p44/p42 MAP kinase pathway, as shown by the blocking effect of PD 98059 and by Western blotting of activated MAP kinases. These findings indicate that FVIIa protease induction of VEGF expression is mediated by thrombin and FXa generated in response to FVIIa binding to TF-expressing fibroblasts; they also exclude a direct signaling involving MAP kinase activation via the intracellular domain of TF when expressed by these cells.

Polymorphisms of the tissue factor pathway inhibitor (TFPI) gene in patients with acute coronary syndromes and in healthy subjects : impact of the V264M substitution on plasma levels of TFPI.

-Mutations of the gene encoding tissue factor pathway inhibitor (TFPI), an inhibitor of TF-induced activation of the coagulation cascade, were screened for in 130 patients and 142 healthy controls to determine whether these variants contribute to acute coronary syndromes or modify plasma TFPI levels. The following 3 new polymorphisms were identified: 384T-->C in exon IV, which does not change the corresponding amino acid (tyrosine 57); -33C-->T in intron 7 (the T/T, C/T, and C/C genotypes were found in approximately 50%, 40%, and 10% of subjects in both groups); and 874G-->A in exon IX (GTG-->ATG), which predicts a valine to methionine change (V264M) in the carboxy-terminus tail of TFPI. The V264M polymorphism was found in 9.2% of the cases and 4.9% of the controls; the associated odds ratio (OR) for acute coronary syndromes was 2.0 (95% confidence interval [CI], 0.7 to 5.1). The OR increased to 3.6 (95% CI, 0.8 to 15.7) and 3.2 (95% CI, 0.9 to 11.8) in nonsmokers and patients without other risk factors, respectively. The possible link between the V264M polymorphism and coronary heart disease was checked in a large case-control study of myocardial infarction (Etude Cas-Témoins de l'Infarctus du Myocarde [the ECTIM Study]). The results showed no link between the V264M polymorphism and coronary syndromes. Interestingly, however, 5 patients heterozygous for the V264M polymorphism had significantly lower plasma TFPI levels than did 13 patients with the most common genotype. Although our present results do not support an association between TFPI polymorphisms and acute coronary syndromes, the possibility that 1 of them, especially the exon IX polymorphism, is associated with subtypes of myocardial infarction or to evolutive particularities that were not assessed in this study, cannot be excluded and is currently being evaluated.

Procedural memory in recent-onset Parkinson's disease.

Parkinson's disease is accompanied by cognitive disorders which may affect procedural memory. Procedural memory uses a specific knowledge resource that expresses itself through pre-established acting procedures. The aim of this study was to better define the characteristics of procedural memory, first of all, by trying to determine the level of involvement of that memory in the acquisition process (during learning and/or during procedure maintenance), then by specifying the effect of the type of resource involved (verbal or motor). To achieve this, we compared the mnestic performances of 20 recent-onset parkinsonian patients with those of 20 healthy controls, using two memory tasks with a fixed rule (poetry, visuomotor tracking). Result analysis revealed that parkinsonian patients had more difficulty than controls in learning the two rules, regardless of the material involved. Their deficiencies were often associated with an impairment of executive functions, and the procedural memory problems described in parkinsonian patients are linked to the involvement of these resources in the various tasks.

Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII.

The transmembrane protein tissue factor (TF) is the cell surface receptor for coagulation factor VII (FVII) and activated factor VII (FVIIa). Recently, TF has been identified as a regulator of angiogenesis, tumor growth, and metastasis. This study was designed to link the binding of FVII(a) to its receptor, TF, with the subsequent triggering of angiogenesis through vascular endothelial growth factor (VEGF) production by human lung fibroblasts. We report that incubation of fibroblasts, which express constitutive surface TF, with FVII(a) induces VEGF synthesis. FVII(a)-induced VEGF secretion, assessed by a specific enzyme-linked immunosorbent assay, was time- and concentration-dependent. VEGF secretion was maximal after 24 hours of incubation of the cells with 100 nmol/L FVII(a) and represented a threefold induction of the basal VEGF level. Reverse transcriptase-polymerase chain reaction analysis of VEGF detected three mRNA species of 180, 312, and 384 bp corresponding, respectively, to VEGF121, VEGF165, and VEGF189. A 2.5- to 3.5-fold increase was observed for the 180- and 312-bp transcripts at 12 and 24 hours, respectively. FVII(a)-dependent VEGF production was inhibited by a pool of antibodies against TF, pointing to the involvement of this receptor. On specific active-site inhibition with dansyl-glutamyl-glycinyl-arginyl chloromethyl ketone, FVIIa lost 70% of its capacity to elicit VEGF production. Consistent with this, the native form (zymogen) of FVII only had a 1.8-fold stimulating effect. Protein tyrosine kinase and protein kinase C are involved in signal transduction leading to VEGF production, as shown by the inhibitory effects of genistein and GF 109203X. The results of this study indicate that TF is essential for VIIa-induced VEGF production by human fibroblasts and that its role is mainly linked to the proteolytic activity of the TF-VIIa complex.

Effect of advanced glycation end product-modified albumin on tissue factor expression by monocytes. Role of oxidant stress and protein tyrosine kinase activation.

Diabetes is associated with a hypercoagulable state that contributes to macrovascular complications, including cardiovascular events. The glycation reaction, a consequence of chronic hyperglycemia, has also been implicated in the pathogenesis of diabetic complications. Glycated proteins have receptors on monocytes and generate reactive oxygen species that can regulate the expression of a number of genes. As abnormal monocyte expression of tissue factor (TF), the main initiator of the coagulation cascade, is responsible for thrombosis in a number of clinical settings, we studied the effect of glycated albumin on monocyte TF expression. Mononuclear cells were incubated with glycated albumin for 24 hours, and monocyte TF activity was measured with a plasma recalcification time assay; TF antigen was measured by ELISA and TF mRNA by RT-PCR. Glycated albumin induced blood monocyte expression of the procoagulant protein TF at the mRNA level. Oxidative stress appeared to be involved in this effect, as the antioxidant N-acetylcysteine diminished TF mRNA accumulation in stimulated monocytes. Hydroxyl radicals, which may be generated inside cells from H2O2 via the Fenton reaction, also appeared to be involved in this effect, as hydroxyl radical scavengers downregulated TF activity and antigen levels (but not TF mRNA). Finally, the involvement of activated protein tyrosine kinase in the transmission of the signal from the membrane to the nucleus was suggested by the inhibitory effect of herbimycin A. These results point to a new mechanism for the hypercoagulability often described in diabetic patients and suggest that antioxidants or protein tyrosine kinase inhibitors might be of therapeutic value in this setting.

Induction of interleukin-1 and subsequent tissue factor expression by anti-proteinase 3 antibodies in human umbilical vein endothelial cells.

OBJECTIVE: To assess the ability of anti-proteinase 3 (anti-PR3) classic antineutrophil cytoplasmic antibodies (cANCA) to stimulate endothelial expression of tissue factor (TF), which is the main initiator of the coagulation cascade that can lead to endothelial injury and thrombosis in patients with Wegener's granulomatosis. METHODS: Human umbilical vein endothelial cells (HUVEC) were grown to confluence and stimulated with affinity-purified anti-PR3 antibodies, Igs from healthy subjects, and endotoxin (lipopolysaccharide) as positive control. RESULTS: TF activity was generated in anti-PR3-stimulated cells, as shown by a chromogenic test. This activity was inhibited by specific anti-TF antibodies. TF messenger RNA (mRNA) was found in anti-PR3-stimulated cells, as detected by reverse transcriptase-polymerase chain reaction, but not in cells stimulated with irrelevant human Igs or Igs from normal control sera. TF expression reached maximum levels 12 hours after exposure to the anti-PR3 cANCA, and did not require complement. TF mRNA expression was inhibited by cycloheximide, suggesting a requirement for protein synthesis. When added to the incubation medium, interleukin-1 (IL-1) receptor antagonist inhibited the induced TF mRNA expression, suggesting that cANCA-stimulated cells initiate IL-1 synthesis. Moreover, cANCA induced IL-1alpha mRNA before TF mRNA. CONCLUSION: This study showed that anti-PR3 treatment of HUVEC induces sequential expression of IL-1alpha mRNA and TF mRNA, as well as their corresponding proteins. Both proteins could have pathogenic roles in the vasculitic process, since TF is the main initiator of the coagulation cascade.

Elevated cyclic AMP inhibits NF-kappaB-mediated transcription in human monocytic cells and endothelial cells.

The NF-kappaB/Rel family of transcription factors regulates the inducible expression of many genes in activated human monocytes and endothelial cells. In this study, we examined the molecular mechanism by which agents that elevate intracellular cAMP inhibit the expression of the tumor necrosis factor alpha (TNFalpha), tissue factor, endothelial leukocyte adhesion molecule-1, and vascular cell adhesion molecule-1 genes. Both forskolin and dibutyryl cAMP, which elevate intracellular cAMP by independent mechanisms, inhibited TNFalpha and tissue factor expression at the level of transcription. Induction of NF-kappaB-dependent gene expression in transiently transfected human monocytic THP-1 cells and human umbilical vein endothelial cells was inhibited by elevated cAMP and by overexpression of the catalytic subunit of protein kinase A (PKA). Elevated cAMP did not prevent nuclear translocation of p50/p65 and c-Rel/p65 heterodimers, decrease nuclear translocation of p65, or significantly modify TNFalpha-induced phosphorylation of p65. Functional studies demonstrated that transcriptional activation of a plasmid containing multimerized kappaB sites by p65 was inhibited by agents that elevate cAMP and by overexpression of the catalytic subunit of PKA. This study indicates that activation of PKA reduces the induction of a distinct set of genes in monocytes and endothelial cells by inhibiting NF-kappaB-mediated transcription.

[Mass screening for colorectal cancer in France. Experience in 165,000 people in the department of Calvados]. / Le dépistage de masse du cancer colorectal en France. Expérience auprès de 165,000 personnes dans le Calvados.

OBJECTIVES: Screening for colorectal cancer is a major public health problem in France as in most developed countries. Several controlled trials are on-going in Europe. The aim of the study was to determine requirements for success of mass-screening for colorectal cancer in France. METHODS: A mass-screening program has been conducted between April 1991 and June 1994 in the department of Calvados for 164,364 people aged 45-74 years. The screening test was first proposed by general practitioners and occupational doctors during appointments. Secondly, a postal invitation to obtain the test, free of charge, by doctor or chemist, was sent. RESULTS: Global participation rate was 43.4%; 40.2% of tests were distributed during the first phase, 47.1% during the second phase and 12.7% were distributed by a private health institute. Participation was higher for females (47.1%) than males (39.2%) and for urban districts (46.5%) than rural districts (24.4%). In case of positive test, colonoscopy has been more frequently achieved in urban districts and when test has been distributed by a physician. Positivity rate was 2.8%. Positive predictive value was 8.0% for a cancer and 13.5% for an adenoma larger than 1 cm. Because both positivity rate and positive predictive value were higher for males than females and increased with age, rate of cancer or large adenoma screened was almost three times higher for males than females and markedly increased with age. CONCLUSIONS: In France, different recruitment methods have to be used to reach a satisfactory participation to a mass-screening campaign. Such a program requires involvement of general practitioners and close coordination between practitioners and health care insurance agencies.

Haemoccult test properties according to type and number of positive slides in mass screening for colorectal cancer.

Despite encouraging results from recent studies, there is still no consensus to undertake mass screening using the Haemoccult test in the general population. The success of mass screening for colorectal cancer depends among other things on Haemoccult test properties. In on-going screening programmes, the Haemoccult test consists of six slides and a test is considered positive if at least one slide is coloured. The aim of this work was to study the influence of the type and number of positive slides on the Haemoccult test's positive predictive value and characteristics of screened lesions. This work focuses on 63,958 first tests in a mass screening programme in Calvados (France) among people aged 45-74 years. There was a linear relation between the positive predictive value for cancer or an adenoma larger than 1 cm and the number of positive slides (P < 10(-4)). The positive predictive value for cancer or large adenoma was significantly higher when 4-6 slides were positive (44.3%) than when only 1-3 were positive (19.1%) (P < 10(-4)). In this latter group, the subjects in whom tumours were detected were younger and had significantly less extensive cancers. Borderline tests (no slides positive and at least one slide with a blue coloration confined to the edges) had a positive predictive value for cancer or an adenoma larger than 1 cm no different to that of tests with 1-3 positive slides. Subjects with borderline results were markedly younger than the others and had less extensive cancers and rectal localisation more often than the others. Our results suggest that (1) increasing the number of positive slides required to declare a test positive leads to an increase in the positive predictive value but is not to be recommended because of the sensitivity of the test and (2) considering borderline Haemoccult tests as positive in on-going and future mass screening campaigns would allow an increase in the sensitivity of the test, especially for rectal cancer and low extensive tumours without any decrease in its positive predictive value.

Participants' characteristics in a French colorectal cancer mass screening campaign.

BACKGROUND: Participation by the target population is clearly a key element in the success of mass screening programs for colorectal cancer. In France, involvement of general practitioners in test distribution is essential to reach a satisfactory participation rate, but other forms of recruitment also have to be organized. The aim of this study was to determine the influence of demographic characteristics such as sex, age, and place of residence on the participation rate in a French mass screening according to different recruitment methods. METHODS: The Hemoccult IIR test was proposed in three consecutive ways: spontaneously by general practitioners and occupational doctors during appointments (phase 1), by postal invitation (phase 2), and finally by direct mailing of the test (phase 3). The target population consisted of 11,947 people between 45 and 74 years of age, living in a district of the French county of Calvados, between March 1991 and April 1993. RESULTS: The overall participation rate was 51.3%. Forty-nine percent of all the tests were done during phase 1, 31% during phase 2, and 20% during phase 3. The overall participation rate varied essentially according to the place of residence, from 65.5% in urban areas and 48.9% in intermediate areas to 27.7% in rural areas. The overall participation rate was also higher for females (57%) than for males (45%) and for those 60 years and older (53.9%) than for those below this age (49.2%). The proportion of tests done during phase 1 was lowest among the youngest and the oldest age groups (37.5% in the 45- to 49-year class and 45.2% in the 70- to 74-year class) and among people living in the rural environment (respectively 55.3%, 45.5%, and 35.9% in urban, intermediate, and rural areas). CONCLUSIONS: This study shows that place of residence strongly influences the global participation rate in mass screening for colorectal cancer in France, whereas sex and age have little influence. Recruitment methods complementary to distribution by general practitioners must be organized, especially for the youngest and oldest age groups (45-49 years and 70-74 years) and above all for people living in rural areas. The social, cultural, and psychological reasons for these differences remain to be investigated, with the aim of adapting mass screening strategies to the different population groups.