Chromosomal abnormalities and ectopic pregnancy? New directions for aetiological research.
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Biomedical subjects
Publications and source records attributed to J Coste.
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The purpose of this paper was to evaluate the reproductive outcome after ectopic pregnancy (EP) from a population-based register in the centre of France. Since 1992, all the women aged 15-44 years, who permanently reside in the target area and who were treated either by surgical or medical procedures for an ectopic pregnancy in one of the area centres, have been registered and prospectively followed until 45 years of age. The analysis presented was based on the 155 women registered between January 1992 and March 1994 who were followed up for at least 6 months, and who were seeking a new pregnancy. The mean follow-up period was 16 months. A total of 102 women (66%) obtained a pregnancy. The first conception was intrauterine for 92 women, and 10 had a recurrence of ectopic pregnancy. Risk factors of recurrence were prior spontaneous abortion and prior tubal damage. For those women who conceived, the mean time to obtain pregnancy ('time to pregnancy') was 4.8 months. The 1 year cumulative intrauterine pregnancy rate (i.e. the probability of obtaining an intrauterine pregnancy within 1 year of seeking pregnancy) was 70%. After multivariate analysis by a Cox regression, the factors associated with higher fertility were age < 30 years, high educational level and no prior tubal damage.
During the past two decades, the incidence of ectopic pregnancy (EP) has doubled or tripled in many parts of the world. In France, EP currently constitutes 2 % of livebirths and 1.6 % of all reported pregnancies. These rates seem presently stable. The main identified risk factors include pelvic inflammatory disease (PID)--in particular that due to Chlamydial infection, previous ectopic pregnancy and cigarette smoking. More than 50 % of EP cases are attributable to infectious factors and cigarette smoking, suggesting dramatic effects on EP rates of appropriate prevention programs. A third risk which could be prevented is induced conception cycles, especially by Clomiphene. Other risk factors are pelvic surgery, previous EP and maternal age (especially over 35 years). Further epidemiologic research is needed to identify new risk factors, to monitor incidence rates and to evaluate the effects of public health policies on EP occurrence. French EP registers will certainly contribute to this research.
Identified risk factors for ectopic pregnancy (prior pelvic inflammatory disease, smoking at the time of conception, intrauterine device, obstetrical and surgical history) explain from 60 to 65% of the cases. Egg anomalies may also be a risk factor as it is likely that the transport of an abnormal egg along the uterine tube is less efficient than a normal one. We tested this hypothesis with data from two case-control studies with the same design covering a total of 1955 women. The risk of ectopic pregnancy increased specifically with age, which is compatible with our hypothesis. We also studied the associations with spontaneous abortion, considered to be a marker of the risk of pregnancies involving chromosomal malformations. We observed an association between ectopic pregnancy and spontaneous abortions (especially recurrent abortions), not explained by other known risk factors. Although our data do not supply a single definitive demonstration, our results converge to suggest that egg chromosomal anomalies may play a part in ectopic pregnancy aetiology.
The reproductive outcome after ectopic pregnancy is evaluated from a population-based register in the center of France. Since 1992, all the women aged 15-44 years, who permanently reside in the target area and who were treated either by surgical or medical procedures for an ectopic pregnancy in one of the area centers, are registered and prospectively followed until 45 years of age. The analysis presented was based on the 221 women registered between January 1992 and December 1994 who were followed up for at least 6 months, and who were seeking a new pregnancy. The mean follow-up period was 19.8 months. 155 women (70%) obtained a pregnancy. The first conception was intrauterine for 136 women, and 19 had a recurrence of ectopic pregnancy. Risk factors of recurrence were prior spontaneous abortion and prior tubal damage. For those women who conceived, the mean time to obtain pregnancy ("time to pregnancy") was 7.6 months. The one year cumulative intrauterine pregnancy rate (i.e. the probability of obtaining an intrauterine pregnancy within 1 year of seeking pregnancy) was 64%. After multivariate analysis by a Cox regression, the factors associated with lower fertility were aged over 30 years, low educational level, history of infertility and prior tubal damage.
Appropriate attention can be directed to quality of life indices in the evaluation of therapeutic interventions only if reliable, valid measurement tools with good sensitivity to change are available. The goal of this study was to validate the French version of the Arthritis Impact Measurement Scales 2 (AIMS2), called EMIR (Echelle de Mesure de l'Impact de la polyarthrite Rhumatoïde) and to compare it with the validated French version of the Nottingham Health Profile, called ISPN (Indicateur de Santé Perceptuelle de Nottingham). The French version of the AIMS2 (37 items, 12 dimensions) was obtained via several independent translations and back-translations, followed by selection of the most relevant items by a panel of experts and a preliminary evaluation in rheumatoid arthritis patients. The measurement properties of EMIR (reliability, validity and sensitivity to change) were investigated in a cohort of rheumatoid arthritis patients who were put under methotrexate therapy and followed up for six months. Reliability was evaluated by test-retest at a ten-day interval (intraclass coefficients of correlation). Principal component factorial analysis was used to study construct validity and Cronbach's alpha coefficients to study internal consistency. Convergent validity was evaluated based on correlations between the quality of life scores obtained in selected dimensions of the EMIR and a number of other parameters (number of painful/swollen joints, pain severity score on a visual analog scale, erythrocyte sedimentation rate). Sensitivity to change after three and six months was determined by calculating mean standardized response means. The EMIR and ISPN were compared based on scores and sensitivity to change for the dimensions that investigated the same concepts. One hundred twenty-seven rheumatoid arthritis patients scheduled for methotrexate therapy were entered into the study. Principal component analysis established that all dimensions of the EMIR were independent from one another, except the "walking and bending" dimension. Internal consistency was satisfactory for each of the 12 dimensions, with Cronbach's alpha coefficients ranging from 0.70 to 0.90. Most correlations between quality of life scores and clinical or laboratory parameters were significant, indicating satisfactory convergent validity. The reliability study also yielded satisfactory results, with intraclass coefficients ranging from 0.65 to 0.90. Sensitivity to change after three and six months was significant for 11 of the 12 dimensions (mean standardized responses, 0.30 to 0.77). Sensitivity to change was slightly better for the EMIR than for the ISPN. Analysis of scores demonstrated that these two instruments did not measure quality of life in exactly the same way but complemented each other.
OBJECTIVE: To develop and validate a cross cultural version of the Arthritis Impact Measurement Scales 2 (AIMS2) to be used by French speaking populations. METHODS: A French version of the AIMS2 was obtained using back translation, committee review, and pretesting. The French AIMS2 was studied in 127 patients with rheumatoid arthritis (RA) about to receive therapy with methotrexate (MTX). Construct validity of the questionnaire was assessed by factor analysis. Convergent validity was evaluated by correlation coefficients with joint counts, pain assessment, and sedimentation rate. Reliability was assessed by test-retest procedure at a 10-day interval, Cronbach's coefficients of internal consistency, and within scale factor analyses. Sensitivity to change after 12 and 24 weeks of therapy with MTX was assessed with computation of standardized response means (SRM) and paired t test comparisons. RESULTS: Factor analyses of the French version clearly identified the same scales of the AIMS2, except for the walking and bending scale which loaded on several factors. Convergent validity of the physical and symptom components of the instrument was demonstrated by significant correlations with clinical and laboratory features. All the scales were reliable (intraclass correlation coefficients: 0.65 to 0.90; percentage of explained variance larger than 50% in all but one scale; Cronbach's alpha: 0.70 to 0.90). Sensitivity to change was demonstrated in 11 of the 12 scales (SRM: 0.30 to 0.77). Most of the improvement was noted by Week 12. CONCLUSIONS: This cross cultural adaptation of AIMS2 in French is valid, reliable, and responsive in patients with RA in whom MTX therapy is instituted. It would permit international comparison studies. This study provides evidence for construct validity and responsiveness of the original version of the AIMS2, not demonstrated previously.
Evaluative composite measurement scales (CMS) are increasingly used in medicine to measure complex constructs in the absence of a reference criterion or 'gold standard'. However, the level of measurement provided by these instruments has usually been given little attention. This paper explores the influence of the characteristics of the item set and weighting on the level of measurement of an evaluative CMS. The approach is illustrated with an application to the scoring system of the Nottingham Health Profile. Simulations are provided to indicate when the composite score of item responses, on an ordinal or pass-fail scale, could be considered to achieve the properties of an interval scale.
Composite measurement scales (CMS) are increasingly used in medicine to measure complex phenomena or concepts such as disease risk and severity, physical and psychological functioning and quality of life. To investigate the methodology currently used in the construction of CMS, we examined 46 studies recently published in six major medical and epidemiological journals. Important measurement properties such as measurement level, content and construct validity and reliability are often neglected. Statistical methods, particularly multivariate methods are frequently misused; verifications of model relevance and assumptions, and cross-validations to avoid overfitting are seldom performed. We propose recommendations for the construction and the presentation of CMS, to help authors and investigators to report and choose, respectively, measurement instruments for a complex phenomenon.
OBJECTIVES: To evaluate the course and frequency of ectopic pregnancy in a single population for a prolonged period in order to study the simultaneous changes in distribution of risk factors, identify new risk factors and evaluate the effect of new diagnostic and therapeutic methods on subsequent fertility and the effectiveness of preventive measures. METHODS: All women residing in the Registry zone and treated surgically or medically for ectopic pregnancy were included in the study and followed to the age of 45 years. RESULTS: In 1992, the incidence of ectopic pregnancy was 20.2 per 1,000 live births (n = 160). At least one currently recognized risk factor was found in 80% of the women. A past history of salpingitis was noted in 13% and nearly one half smoked or had smoked at the time of conception. Nineteen percent had a past history of pelvic surgery and 19% had a history of infertility. The ectopic pregnancy recorded was the second one in 9%. Nearly one-third of the ectopic pregnancies recorded (31%) were diagnosed in patients with a intrauterine device. None of these latter patients had other risk factors. Vaginal echography was used for diagnosis in 75% of the cases. Surgery was used as first intention treatment in 94% and medical treatment (methotrexate) was used in 6%.
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OBJECTIVE: To examine the clinicopathologic features of the noncompressive neuropathies in rheumatoid arthritis (RA). METHODS: We studied 32 patients with RA and peripheral neuropathy whose nerve and/or muscle biopsy specimens exhibited necrotizing vasculitis. Morphologic analysis of nerve specimens included light and electron microscopy studies and teased fiber preparation. Survival was evaluated, and the prognostic values of clinical, biologic, and pathologic features were assessed by Cox proportional hazards model. A prognostic assessment based on the significant variables was devised to estimate the probability of survival of any individual patient. RESULTS: Epi- and/or perineurial vasculitis was observed with the same frequency in the 17 patients with sensory and motor deficit and the 15 patients with sensory neuropathies and was associated with axonal degeneration of an average of 77.7% of the nerve fibers. The mean followup was 7.2 years, and the overall survival rate at 5 years was 57%. A full prolonged remission of the vasculitis was observed in 53% of the patients; relapse occurred in 25%. The factors correlated with mortality, in decreasing order of significance, were clinical cutaneous vasculitis (P = 0.0003), neuropathy affecting 3 or 4 limbs (P = 0.03), and depressed level of C4 (P < 0.05). The prognostic assessment indicated a wide range of 5-year probabilities of survival, from < 1% to 93%. CONCLUSION: Necrotizing vasculitis is responsible for the different patterns of noncompressive neuropathies in RA, including mononeuritis multiplex and distal symmetric sensory or sensorimotor neuropathy. Cutaneous vasculitis, multifocal neuropathy, and depressed C4 level were the 3 independent variables which best predicted mortality. We propose a prognostic assessment according to these variables, to stratify patients to receive more aggressive or less aggressive therapy.
BACKGROUND: To verify the criteria for human T-lymphotropic virus (HTLV) seropositivity in Western blot (WB) proposed by the Retrovirus Study Group of the French Society of Blood Transfusion, 186 blood donations that were repeatedly reactive in HTLV enzyme-linked immunosorbent assay, selected according to their WB pattern, were tested by polymerase chain reaction (PCR) and radioimmunoprecipitation assay (RIPA). STUDY DESIGN AND METHODS: In two commercially available WBs, 12 samples were confirmed as positive (rgp21+p19+p24) and 174 were interpreted as indeterminate (one or two reactivities to these proteins). The primer pairs used for the PCR allowed the amplification of type I (HTLV-I) or type II (HTLV-II) (or both) sequences. The RIPA was performed with two 35S-labeled cell lines: HTLV-I infected HUT 102/B2 and HTLV-II-infected MoT. RESULTS: Of the 12 positive samples, 11 were classified as HTLV-I-positive and one as HTLV-II-positive. Among the 174 indeterminate samples, three (WB pattern: rgp21+, p19+, p24-) were HTLV-I positive in PCR (one of them was positive in RIPA also); the other 171 were HTLV negative. CONCLUSION: In the study of a population in which 97 percent of HTLV infections are due to HTLV-I, these data support the three-protein criteria (rgp21, p19, and p24) for a positive blot reading. No HTLV infection was observed when rgp21 did not react. Consequently, p19 and/or p24 band patterns represent false reactivity and do not require PCR or RIPA confirmation. To discriminate between false- and true-positive results in the absence of MTA-1 or K55 reactivity, PCR and/or RIPA is required only when rgp21 reactivity is associated with one gag band (p19 or p24).
RATIONALE AND OBJECTIVES: To assess the intraobserver reliability of three methods used frequently to evaluate joint destruction in rheumatoid arthritis: the Sharp method, the Larsen method, and the carpo:metacarpal ratio. METHODS: One observer analyzed twice within a 6-week interval 71 radiographs from patients with rheumatoid arthritis. Reliability was estimated by intraclass correlation coefficient (R) and by Altman-Bland graphical method. Correlations were examined by the Spearman's coefficient (r). RESULTS: The intraobserver reliability of each method appeared satisfactory with a good result for the Sharp method (R = 0.97). The correlation was strong (r > 0.80) between the results obtained by Sharp's and Larsen's methods and weaker between the results of the two former methods and the carpo: metacarpal ratio. CONCLUSIONS: Sharp's method should be used preferentially in studies evaluating the radiologic changes in rheumatoid arthritis over time, especially in clinical trials. The carpo:metacarpal ratio may be considered as a complementary method, when wrist destruction is of conceptual importance.
OBJECTIVE: Glucocorticoids are powerful antiinflammatory agents widely used for the treatment of rheumatoid arthritis (RA). Synthesis and/or secretion of annexin I (A-I) is induced by these steroids. Annexins V and VI are also found extracellularly but are not induced by glucocorticoids. Annexins may be potent antagonists of phospholipase A2 (PLA2). Since autoantibodies to A-I have been reported in patients with RA, we studied the reactivity of sera from patients with RA to A-V and A-VI. METHODS: Sera from 26 patients with RA were assessed for anti-A-V and anti-A-VI antibodies and compared with sera from 26 sex/age matched healthy subjects. IgG and IgM antibodies were analyzed in an ELISA: A correlation study with disease activity and corticosteroid treatment schedule was performed. RESULTS: Sera from patients with RA contained significantly higher levels of IgG [anti-A-V and anti-A-VI] autoantibodies than control sera, both being correlated. This rise in antiannexin antibody titers was correlated with the RA activity score, and negatively correlated with the daily dose of corticosteroids. CONCLUSION: High levels of IgG (anti-A-V and anti-A-VI) antibodies were found in sera from patients with RA. We suggest that antiannexin autoantibodies may play a role in the clinical course of RA by impairing the anti-PLA2 effect of annexins.
This study aimed to explore the clinical and psychological features of non-specific low-back pain (LBP), and to evaluate a classification of patients based on the relationship between psychological disturbances and LBP clinical presentation. An unselected population of consecutive patients (n = 262) complaining of low-back pain to primary care physicians of the Epidemiology Team of the French Rheumatology Society, in October and November 1991, was studied. Measures included a standardized clinical evaluation of the back and a psychological assessment using the General Health Questionnaire. Ninety nine patients (38%) were classified as having a psychological disorder. The following symptoms: psychological precipitating event, permanent pain at night, diffuse spinal pain, pain increased by changing climate, pain increased by psychological factors, dysesthesias in the back, non-anatomical tenderness, were found to be closely associated with the existence of psychological disorder. Correspondence and cluster analyses provided support for the four-group classification of low-back pain previously devised. This classification may be interpreted through the relationships between psychological disturbances and the back clinical features. Although the study was mainly descriptive and used a cross sectional design, its results underline the importance of psychological influence on low-back pain presentation, and suggest the interest of a psychiatric assessment in low-back pain patients. Psychological disorders appear to be frequent in these patients and specific management of these disorders may prove useful.
Hard, objective data to evaluate outcome in patients with rheumatology diseases is not only difficult to obtain, but often poorly correlated with the degree of the functional incapacity caused by these non-fatal but disabilitating diseases. Soft, subjective data does not meet the traditional criteria for scientific research. However, due to important advances in the field of psychometry and its medical applications, we now have adequate instruments to evaluate quality of life, the major outcome parameter in patients with chronic rheumatic diseases. The Arthritis Impact Measurement Scales is the most widely used and is particularly adapted to patients with rheumatoid arthritis. Other scales include the Health Assessment Questionnaire, the Nottingham Health Profile, and the Sickness Impact Profile. Most of the studies conducted in the field of rheumatology concern patients with rheumatoid arthritis or osteoarthritis of the lower limbs. Quality of life measures can however be applied to most all the different clinical situations including low back pain, ankylosing spondylitis and systemic diseases. Quality of life measures will play an important role in treatment evaluation procedures. They correspond to real progress in responding to the legitimate demand of patient with chronic diseases for effective validated health care.