A workers' health surveillance online training programme for occupational physicians.

BACKGROUND: To support occupational physicians (OPs) in the implementation of workers' health surveillance (WHS), a training programme was developed. AIMS: (i) To evaluate the effects of a WHS training programme for OPs on knowledge, self-efficacy and skills to implement WHS. (ii) To evaluate to what extent a WHS training programme is acceptable and feasible for implementation in practice. METHODS: A single-blinded randomized controlled trial with waiting-list control group was used. The WHS training programme consisted of an e-learning and a 4.5-h online training session. OPs completed a knowledge test (0-8), self-efficacy questionnaires on knowledge and skills (6-60), and vignette assignments (0-16) to measure skills. OPs completed the questionnaires, either before and after the WHS training programme (intervention group), or before the training programme (control group) while receiving the training programme after the waiting period. All OPs completed questionnaires about the training's acceptability, and feasibility for implementation in practice. ANCOVA and Poisson regression analyses were conducted. RESULTS: The self-efficacy score (M = 44.1 versus M = 37.2) (P < 0.001) and skills score (M = 9.6 versus M = 8.3) (P < 0.05) of OPs in the training group (N = 16) were higher than the control group (N = 23). No effect was found on knowledge. Evaluation of acceptability and feasibility showed that 21 (58%) OPs were very satisfied with the training part on initiating WHS, and 29 (85%) would recommend the WHS training programme to colleagues. CONCLUSIONS: This WHS training programme has a positive effect on self-efficacy and skills of OPs to implement WHS, and may be acceptable and feasible to implement in practice.

Workers' health surveillance targeting mental health: evaluation of a training.

BACKGROUND: Mental health complaints occur frequently among healthcare workers. A workers' health surveillance mental health module (WHS-MH) was found to be effective in improving work functioning of nurses, although not implemented regularly. Therefore, training for occupational physicians and nurses to facilitate the implementation of WHS-MH was developed and evaluated. AIMS: This study was aimed to evaluate the effect of training on knowledge, self-efficacy and motivation to implement WHS-MH, and to evaluate participants' satisfaction with the training. METHODS: Three-hour training was held among 49 occupational physicians and nurses in the Netherlands. Effect on knowledge, self-efficacy and motivation was assessed using knowledge tests and questionnaires before and immediately after the training. Satisfaction with the training was measured using questionnaires after the training. RESULTS: A mean knowledge test score of 5.3 (SD = 1.6) was found before training, which did not significantly increase after training (M = 5.6, SD = 1.8). In total, 43% agreed or strongly agreed to have sufficient skills to implement WHS-MH, which significantly increased to 78% after the training. Furthermore, 87% agreed or strongly agreed to be motivated to initiate WHS, which significantly increased to 94% after the training. The majority of participants were satisfied with the training. CONCLUSIONS: Training may enhance the implementation of the WHS-MH through increasing self-efficacy and motivation. However, no effect on level of knowledge to implement WHS-MH was found.

The risk of spina bifida aperta after first-trimester exposure to valproate in a prenatal cohort.

Use of antiepileptic drugs (AEDs) during pregnancy is associated with an increased risk of congenital malformations. Spina bifida aperta has been linked specifically to valproic acid (VPA) (estimated risk, 1 to 2%). The actual risk, the exclusive association of VPA with spina bifida and not anencephaly, and the precise causative relation remain matters of discussion. A prospective cohort study of pregnant women with epilepsy receiving AEDs and referred for prenatal diagnosis before week 22 of gestation was conducted, with follow-up to 3 months after birth. Pregnancies (291 singleton and 6 twin) in 261 women were evaluated. The prevalence of anomalies after exposure to any AED was 6.9%. For fetuses exposed to VPA, the prevalence was 9.4%, including six cases of spina bifida, two of which were in monozygotic twins (giving a prevalence rate of 6.3%, or 5.4%, if twins counted as one). Spina bifida was associated with a significantly higher average daily dose of VPA as compared with pregnancies with normal outcome (1.640 +/- 136 mg/d vs 941 +/- 48 mg/d, p = 0.0001). No relation was observed between the occurrence of spina bifida and type of maternal seizure or epilepsy, family history of epilepsy or neural-tube defects, or medical history. From these results we suggest that when the use of VPA during pregnancy cannot be avoided, the teratogenic risk might be diminished by reduction of the daily dose.

Acceptance of chorionic villus sampling in the southwest region of The Netherlands: a 5-year evaluation.

The acceptance of chorionic villus sampling (CVS) for monitoring pregnancies at risk for chromosomal and genetic disorders was studied from its introduction in the Centre for Clinical Genetics in Rotterdam in 1984 until 1988. Special attention was given to increasing acceptance in the group with advanced maternal age (AMA) (12.6% CVS in 1984, 52.2% CVS in 1988) and the group with a high genetic risk (HGR) (42.7% in 1984, 86.7% in 1988). The odds-growth-rate in CVS was 1.64 and 1.67 respectively, which was not significantly different. The relatively limited use of CVS at AMA is most likely determined by the fact that a considerable number of patients are referred too late in pregnancy to have the option of CVS.

Case of 45,X/46,XY mosaicism with non-mosaic discordance between short-term villi (45,X) and cultured villi (46,XY).

We report on a prenatally detected case of discordant non-mosaic karyotypes following chorionic villus sampling. A 45,X karyotype was found in cytotrophoblast cells and a 46,XY karyotype in mesenchymal core cells. A subsequent amniocentesis showed a true 45,X/46,XY mosaicism. Confirmatory studies, including fluorescence in situ hybridization (FISH) in various fetal and placental tissues as well as in the original villi preparations changed the presumed condition of generalized mosaicism with culture confined normality to that of generalized mosaicism with absolute concordance. This case underscores the importance of the investigation of both short-term and cultured villi preparations, the implementation of prenatal FISH studies, and the need for thorough follow-up investigation in cases of discrepant results.

Prenatal detection of trisomy 18 caused by isochromosome 18p and 18q formation.

We report on the prenatal detection and further genetic studies in a case of trisomy 18 caused by isochromosome 18p [i(18p)] and 18q [i(18q)] formation. The diagnosis was made by standard cytogenetic techniques in amniotic fluid cells and confirmed by fluorescence in situ hybridization. The formation of the isochromosomes cannot be explained by a single model; centromere misdivision and meiosis II nondisjunction without recombination or mitotic misdivision are the most likely mechanisms of formation as indicated by DNA analysis.

Interpretation of chromosome mosaicism and discrepancies in chorionic villi studies.

In 3,000 chorionic villi studies (CVS) 33 cases of mosaicism and 7 false-positive cell lines in all cells were seen. The mosaic cell lines were caused by aneuploidy of autosomes (13x), sex chromosomes (9x), and structural anomalies (11x). Mosaics of fetal origin were only 4 cases of trisomy 21 and one 47,XXY mosaic. In 7 cases abnormal karyotype of non-fetal origin was seen in all cells in direct studies, including trisomy 16 (3x) and trisomy 18 (2x). The combined use of direct CVS and cell cultures always uncovered the non-fetal origin of chromosome abnormalities and the study of cultured cells in all cases could have prevented 5 terminations. Complete follow-up studies demonstrated no false-negative results. Therefore, CVS can be nearly 100% accurate when both direct studies and cultures are examined in cases of mosaicism and other cell lines of possible non-fetal origin, such as trisomy 16, trisomy 18, translocation (21;21), and 45,X cells.

Terminal transverse limb defects and early chorionic villus sampling: evaluation of 4,300 cases with completed follow-up.

Data from 4,300 consecutive cases following prenatal diagnosis by transcervical (TC) CVS (n = 1,570) and transabdominal (TA) CVS (n = 2,370) were evaluated. In the follow-up study only infants examined by a physician were included. Gestational age varied between 8.5 and 11.6 weeks (mean 10.3 weeks) for TC-CVS and between 9.3 and 20 weeks (mean 12.3 weeks) for TA-CVS 98% of TC-CVS was performed at 9-10 weeks, 80.7% of TA-CVS procedures were carried out at 12-15 weeks. Selective termination took place in 97 cases of TC-CVS (6.1%) and in 72 cases of TA-CVS (2.6%). Another 8 women had a termination for psychosocial reasons, resulting in 4,123 (1,469 TC, 2,654 TA) continuing pregnancies. The overall fetal loss rate < 28 weeks was 5.4% (n = 80) for TC-CVS and 2.6% (n = 70) for TA-CVS. The overall incidence of congenital abnormalities after birth was 0.9%. Two terminal transversal limb defects were detected in the TC-CVS group (0.14%) against one (0.04%) in the TA-CVS group.

Prenatal diagnosis of cystic kidney disease with ventriculomegaly: a report of six cases in two related sibships.

In 2 consanguineous relationships, a Cape Verdian man fathered six fetuses (5 male) with fetal ventriculomegaly and echodense fetal kidneys as visualized by ultrasonography between 16 and 32 weeks. During prenatal monitoring, an increased alpha fetoprotein level and abnormal acetylcholinesterase were detected at amniocentesis in 5 of 6 affected fetuses. Chromosomes were normal. Five pregnancies resulted in elective termination; one child was still-born prematurely. Hydrocephalus and cystic disease of the (renal) cortico medullary areas were found. One fetus had polydactyly. The differential diagnosis and prenatal diagnosis of this presumably autosomal recessive syndrome are discussed.

Ring chromosome 18 in a fetus with only facial anomalies.

We report on a prenatally detected case of ring chromosome 18 [46,XX,r(18)] in amniotic fluid cells of a fetus with an abnormal facial profile on ultrasound as the only malformation. The chromosome 18 origin of the ring chromosome, of a supernumerary marker chromosome in some cells, and of micronuclei was demonstrated by fluorescent in situ hybridization with a whole chromosome 18 paint (Cambio) and 18 centromere probe L1.84. DNA investigations showed deletions of 18p as well as 18q material of r(18), which turned out to be of paternal origin. Autopsy of the fetus after termination of pregnancy at 20 weeks of gestation showed no additional malformations, in agreement with the previous ultrasound findings.

Transabdominal chorionic villus sampling in a multiple pregnancy at risk of argininosuccinic aciduria: a case report.

We report on a 32-year-old G3P2 woman at increased risk of argininosuccinic aciduria in her offspring. In her first infant, the disease was diagnosed at age 3 months. In the second pregnancy, the disorder was excluded following incorporation of radio-labeled 14C-citrulline in intact chorionic villi obtained through transcervical chorionic villus sampling at 10 weeks gestation. Twins were diagnosed in the third pregnancy. Separate transabdominal chorionic villus sampling of both fetuses was carried out at 10 weeks gestation. Chromosome analysis demonstrated a normal male and female karyotype. Incorporation of radio-labeled 14C-citrulline in intact villi was deficient in both villus samples, establishing the diagnosis of argininosuccinic aciduria in both fetuses. The present results confirm the reliability of direct analysis of villi for the diagnosis of argininosuccinic aciduria.

Nasopharyngeal teratoma and mosaic tetrasomy 1q detected at amniocentesis. A case report and review of the literature.

The occurrence of nasopharyngeal teratomas (NPT) is an infrequent event and prenatal detection of such tumors is even rarer. We present a case report and review of the literature (N = 78 cases), in which we describe the cytogenetic, DNA, and pathological findings of a fetus with a mature NPT which was detected prenatally by ultrasound investigation following complaints of severe polyhydramnios by the mother.

Prenatal diagnosis of Niemann-Pick disease type C.

Niemann-Pick disease type C (NPC) was demonstrated in two successive pregnancies by strongly reduced activity of sphingomyelinase in amniotic fluid cells. By contrast, chorionic villi from the first pregnancy had shown normal sphingomyelinase activity. The prenatal diagnosis of NPC in the two fetuses was confirmed, after termination of the pregnancies, by (phospho)lipid analyses of the fetal livers, by the assay of sphingomyelinase in the fetal fibroblasts and by the demonstration of a defective esterification of exogenous cholesterol and of cholesterol accumulation by filipin staining. Retrospective analysis of cultured amniocytes for cholesterol esterification and filipin staining confirmed the feasibility of these methods for prenatal diagnosis. In a recent pregnancy in the same mother the three available methods were applied to amniotic fluid cells and an unaffected child was correctly predicted. Lipid analysis of liver tissue from the patient with NPC and the two fetuses showed a 3-5 times increased level of cholesterol, a 2-3 times increased level of sphingomyelin and a remarkable increase of bis (monoacylglyceryl) phosphate.

Prenatal diagnosis of ataxia-telangiectasia and Nijmegen Breakage syndrome by the assay of radioresistant DNA synthesis.

Prenatal diagnosis was performed in 16 pregnancies at risk of ataxia-telangiectasia (A-T) or Nijmegen Breakage Syndrome (NBS). Radioresistant DNA synthesis (RDS) was investigated in cultured chorionic villus (CV) cells and/or amniotic fluid (AF) cells. In four pregnancies, an affected foetus was diagnosed with increased RDS in cultured CV cells. In three of the four cases confirmation of the diagnosis was obtained by analysis of AF cells and/or skin fibroblasts from the foetus cultured after termination of the pregnancy; in the fourth case a fibroblast culture from the aborted foetus failed. In one case, only AF cells could be analysed in a late stage of pregnancy; pregnancy was terminated due to intermediate/equivocal results but the foetal fibroblasts showed normal RDS. Normal RDS was demonstrated in the other 11 pregnancies at 25% risk either by analysis of CV cells (nine cases) or of AF cells (two cases). In some cases the (normal) results on the CV cells were corroborated by subsequent analysis of AF cells. The results suggest that RDS analysis of CV cells allows reliable prenatal diagnosis of A-T/NBS. However, amniocentesis may be necessary to confirm normal results on CV cells if the foetus is female (because of the risk of maternal cell contamination) or in the rare case of equivocal results.

Evaluation of severe insomnia in the general population: results of a European multinational survey.

The epidemiology of severe insomnia and its effect on quality of life and healthcare consumption was assessed in a survey of the general population of five northern European countries. Applying established consumer sampling techniques, insomnia sufferers were selected from the general population using a questionnaire, conducted by face-to-face interview, and severity of insomnia was ranked (severe, mild/moderate, no sleep complaint) using a specific algorithm. Population samples were matched according to case control methodology for age, gender and geographical region. A second questionnaire gathered information on sleep problems, quality of life (SF-36 scores) and healthcare consumption. The prevalence of severe insomnia ranged from 4% to 22%, was higher in females than in males, but did not increase significantly with age. Patients with severe insomnia had been experiencing sleeping problems for a median of 2-6 years. In all countries, insomnia had a negative impact on quality of life, and the degree of impairment in quality of life was directly related to the severity of insomnia. Individuals with severe insomnia also showed a higher level of healthcare consumption. Despite this, severe insomnia did not appear to feature prominently in the doctor-patient relationship.

Quality-of-life outcomes and the use of antihistamines in a French national population-based sample of patients with perennial rhinitis.

Our primary objective in designing the first large-scale nationwide population-based survey in France was to assess the impact of perennial rhinitis on quality of life. Our secondary objective was to describe the use of drug treatment, including histamine H1 antagonists, in that population. A pollbase of 20,000 households was screened for symptoms of rhinitis. 16,786 households responded, including 35,615 patients aged over 15 years, giving an overall response rate of 84%. Using an algorithm, 1367 patients with probable perennial rhinitis were selected for a cross-sectional collection of data about the history of their condition, comorbidity, use of medical resources, sick leave and nasal symptom-related quality of life [according to the Medical Outcomes Study 36-Item Short-Form Questionnaire (SF-36)]. Finally, multivariate regression techniques were used to describe the relationship between quality-of-life scores and treatment subgroups, controlling for some other confounding factors. The point prevalence of perennial rhinitis was estimated to be 4.1% [95% confidence interval (CI): 3.9 to 4.3%]. Association of perennial rhinitis with a history of asthma was highly significant (13.4% in those with perennial rhinitis vs 3.8% in those without; odds ratio 3.26; p < 0.001). 38% of the patients with perennial rhinitis reported having taken regular medication during the last 3 months. Antihistamine use was associated with use of decongestant or topical nasal products in about one-third of patients. Four SF-36 dimensions (physical functioning, role physical, bodily pain, social functioning) showed significantly higher mean scores (indicating better quality of life) in patients receiving non-anticholinergic histamine H1 antagonist therapy, relative to those receiving other treatments, a difference that was maintained after controlling for gender, age, level of nasal symptoms, medical history of asthma and number of general practitioner visits. These results established the long term impact of perennial rhinitis on quality of life (generic and specific), and raised questions about appropriate therapy, since a positive association between current use of non-anticholinergic antihistamines with improvements on some SF-36 dimensional scores in patients with perennial rhinitis was observed.

Chromosome analysis of small and large L5178Y mouse lymphoma cell colonies: comparison of trifluorothymidine-resistant and unselected cell colonies from mutagen-treated and control cultures.

Mutagenesis assays at the thymidine kinase (TK) locus in L5178Y mouse lymphoma cells frequently yield mutant colonies with a bimodal size distribution. The objectives of this study were to determine whether a relationship exists between mutant colony size and chromosomal aberrations and whether the colony-size distributions obtained from this assay can indicate the clastogenic activity of a test chemical. Cells from 8 different types of L5178Y mouse lymphoma cell colonies were examined for chromosomal abnormalities within 10 cell generations after colony isolation. The colonies included small (sigma) and large (lambda) unselected cell (UC) and trifluorothymidine-resistant (TFTr) colonies derived from TK +/- cell cultures treated with the solvent dimethyl sulfoxide (DMSO) or hycanthone methanesulfonate (HYC). Chromosome abnormalities were present in cells from 12% (7/60) of the UC colonies, but there was no apparent relationship between colony diameter and the presence of chromosomal abnormalities. Abnormalities affecting chromosome 11, which is believed to be the site of the TK gene, were not observed in cells from UC colonies. Abnormalities affecting chromosome 11 were observed only in cells from sigma-TFTr colonies irrespective of whether they were spontaneous (5/15 colonies) or induced by HYC (4/15 colonies). Overall, 30% (9/30) of sigma-TFTr colonies had cells with an abnormal chromosome 11 and 10% (3/30) had abnormalities affecting other chromosomes. Abnormalities affecting chromosome 11 were not observed in cells from lambda-TFTr colonies (0/30 colonies). The observation of only 30% of sigma-TFTr colonies with chromosome damage affecting chromosome 11 indicates that other mechanisms, in addition to chromosome damage at the level of resolution used in this study (i.e., 200-300 chromosome bands). contribute to small TFTr colony size.

Cordocentesis for rapid karyotyping in fetuses with congenital anomalies or severe IUGR.

The objective was to determine the role of percutaneous umbilical blood sampling (cordocentesis) as a rapid technique for chromosome analysis in a high risk obstetric population. Cordocentesis was attempted in 167 pregnant women (168 fetuses) with IUGR, a single anomaly or multiple anomalies. Gestational age ranged between 17 and 37 weeks. The procedure was successful in 152 (90%) fetuses with a blood sample withdrawan at first attempt in 80%. Neither technique was associated with any false negative or false positive findings. Postprocedural complications included one case of persistent fetal bradycardia, but no fetal death. In nine cases amniotic fluid was collected, resulting in 161 fetal blood or amniotic fluid samples for chromosome analysis. An abnormal chromosome pattern (n = 26) was established in 1/12 cases (8%) of severe IUGR, 6/88 cases (7%) with a single structural anomaly and 19/61 cases (31%) with multiple structural anomalies. In the presence of an abnormal chromosome pattern, the perinatal mortality rate was as high as 96%. There is a high association between multiple fetal anomalies and abnormal chromosome pattern.

The 1999 French Venous Disease Survey: epidemiology, management, and patient profiles.

A recent (1999) Sofres survey of representative samples of the adult French population aged 15 and over showed that almost half this population suffered from lower limb venous complaints and that 43% of them were untreated. Of those treated, 24.2% received venotropics, including 21.5% by prescription, while 6.0% practiced self-medication. Venous disease sufferers form a relatively underprivileged sector of the population in terms not only of age, income, work and living conditions, but also of general health and medical history. Despite its clinical efficacy and potential social utility, venotropic treatment is possible only if backed by adequate state health insurance coverage supplemented by mutual and private insurance schemes. Any restriction to such coverage will only decrease access to prescription venotropics.

[Descriptive study of digestive functional symptoms in the French general population]. / Etude descriptive des symptômes fonctionnels digestifs dans la population générale française.

UNLABELLED: To study the prevalence of "reported" functional digestive symptoms (FDS) in terms easily understood by the general population without resorting to predefined concepts of functional syndromes, and to assess FDS impact on public health, a sample survey has been carried out between September and December 1995. METHODS: Four thousand eight hundred and seventeen subjects representative of the French general population aged 15 years or more filled in a questionnaire describing their digestive disorders. RESULTS: Seventy percent of the subjects had digestive complaints, 9% being related to a presumably organic disease, and 61% attributed to FDS. Twenty-seven % of the subjects claimed to be inconvenienced by their FDS, whereas 34% seemed not to feel any inconvenience. Among FDS, gas emission was the most frequent symptom (59%), followed by stomach ache and/or digestive pain (48%), flatulence (47%), bad digestion sensations (40%), constipation (35%), aerophagia (29%), bad breath (22%), incomplete evacuation of stools (19%). FDS had lasted from 6 months to 5 years in 38%, and over 5 years in 52%. In the subgroup of subjects inconvenienced by FDS (27%), 9% consulted and 18% did not, whereas in the subgroup not inconvenienced, 3% consulted and 31% did not. Altogether, 26% of the subjects followed a prescription or self medication treatment; 35% were not treated. Some explanatory variables appeared to be associated with the onset of inconvenience: the associations pain and bad digestion, flatulence and aerophagia, incomplete evacuation and nervous or presumably organic origin of FDS, age, stress, FDS frequency. Duration of symptoms, age above 65 years, digestive pain, presumably organic origin, and FDS frequency were associated with the need to consult. This descriptive, pragmatic survey shows the widespread prevalence of FDS, affecting 28 million French people. Functional digestive disorders in the "academic" meaning constitute only a limited subset. FDS lead to major health care consumption. Their impact on public health is undoubtedly greater than the estimates derived from studies designed in accordance with conventional nosological categories.