Personalized health care (PHC) or precision medicine is a new medical concept that aids in treatm... more Personalized health care (PHC) or precision medicine is a new medical concept that aids in treatment decisions for patients by tailoring them to their individual needs. It often employs genetic testing to select appropriate and optimal therapies (pharmacogenomics). Although this concept is widely applied in oncology, the field of hypertension is still in the early stages and "personalization" is currently limited to tailoring antihypertensive treatment according to age, comorbidities, and ethnicity. Despite the fact that incomplete/lack of treatment response occurs in 10-30% of hypertensive patients for angiotensin-converting enzyme (ACE) inhibitors and in 15-25% for β-blockers, major continental guidelines still recommend the use of antihypertensive agents in a "onesize-fits-all" approach, neglecting the 1977 postulation of the Joint National Committee that "all patients must receive individualized therapy programs." The arrival of molecular testing offers new possibilities to differentiate monogenetic from polygenetic disorders and to identify associations between hypertension and drug response to corresponding genes. Up to 50% of the variation in blood pressure (BP) is attributable to genetic factors. Polymorphisms have been identified and studied in genes for BPmodifying receptors, such as ADBR (β-adrenergic receptors), and pharmacological pathways (GNB3, RAAS system). Approximately, one-quarter of the currently analyzed gene polymorphisms demonstrate significant pharmacogenetic effects (ADD1 Gly460Trp and the insertion/deletion [I/D] polymorphism in intron 16 of the ACE gene). Several large screening studies are currently ongoing to assess the impact on efficacy of antihypertensive medication of variants in hypertension-susceptibility genes. The GenHAT substudy of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) assessed the predictive validity of the ACE I/D genotype for coronary heart disease. The Family Blood Pressure Program included 11,079 participants to map genetic variants associated with hypertension. In this review chapter, we display the current body of knowledge regarding PHC in the treatment of hypertension. In particular, we highlight genetic variants associated with hyperten
Clinical Chemistry and Laboratory Medicine (CCLM), 2014
Background: This study aims to evaluate the performance of the soluble Fms-like tyrosine kinase-1... more Background: This study aims to evaluate the performance of the soluble Fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio to predict early-onset, preterm and severe preeclampsia at mid-pregnancy in asymptomatic women. Methods: Based on a prospective cohort of 7929 pregnant women from the Quebec City metropolitan area, a nested case-control study was performed including 111 women who developed preeclampsia and 69 women with gestational hypertension matched with 338 normotensive women. Serum sFlt-1 and PlGF were measured between 20 and 32 weeks of gestation. The performance of the sFlt-1/ PlGF ratio, expressed as raw values and multiples of the median (MoM) for the prediction of early-onset, preterm and severe preeclampsia was evaluated. Results: Women who developed preeclampsia had significantly higher MoM sFlt-1/PlGF ratio (p < 0.001). In the early-onset preeclampsia group, the median of the MoM distribution was 24.0 and the area under the receiver operating characteristic curve (AUC) was 0.977, giving sensitivities of 77.8% and 88.9% at false-positive rates of 5% and 10%. Positive predictive values (PPV) were 2.5% and 1.5%, respectively. In a subset between 26 and 32 weeks of gestation, at a threshold of 30, the sFlt-1/PlGF ratio yielded 100% specificity and identified, respectively, 85.7% and 65.2% of women who developed early-onset and preterm preeclampsia. Conclusions: The sFlt-1/PlGF ratio has the potential to predict early-onset and preterm preeclampsia at midpregnancy in asymptomatic women. However, care must be paid to the prevalence of early-onset preeclampsia in the population since low prevalence reduces PPV and may hamper clinical utility.
Details of the assumed interventions according to intensity of patient management. Summary of int... more Details of the assumed interventions according to intensity of patient management. Summary of interventions that may be performed under each management level according to German maternity policy guidelines and the S1-guideline for hypertensive pregnancy illnesses. (DOCX 16 kb)
Comparison of UK and German economic models. Key similarities and differences between the UK [1] ... more Comparison of UK and German economic models. Key similarities and differences between the UK [1] and German economic models used to determine the incremental value of the sFlt-1/PlGF ratio test (cut-off 38) for guiding the management of women with suspected preeclampsia are presented. (DOCX 16 kb)
Objective: The Elecsys ® immunoassay sFlt-1/PlGF ratio and the Triage ® PlGF assay were compared ... more Objective: The Elecsys ® immunoassay sFlt-1/PlGF ratio and the Triage ® PlGF assay were compared (in a prospective, multicenter, case-control study) for diagnosis of preeclampsia/hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. Methods: Women in European perinatal care centers with singleton pregnancies were enrolled: 178 cases had confirmed preeclampsia and 391 controls had normal outcome. Patients in the preeclampsia/HELLP syndrome group were matched pairwise by gestational week to healthy controls (1:2). Maternal blood samples were analyzed using (a) fully automated Elecsys PlGF and Elecsys sFlt-1 immunoassays with two cutoffs (early-onset [<34 weeks] ≤33, ≥85; late-onset [≥34 weeks] ≤33, ≥110), and (b) Triage PlGF immunoassay (single cutoff). Diagnostic performance and utility were assessed. Results: Respectively, 83 and 95 women had early-onset or late-onset preeclampsia/HELLP syndrome. The overall diagnostic performance of the Elecsys immunoassay sFlt-1/PlGF ratio (area under the curve [AUC] 0.941) was higher than for Triage PlGF (AUC 0.917). The Elecsys immunoassay sFlt-1/PlGF ratio sensitivity and specificity was: 94.0% (95% confidence interval [CI] 86.5-98.0) and 99.4% (95% CI: 96.8-99.9) for early-onset preeclampsia; and 89.5% (95% CI: 81.5-94.8) and 95.4% (95% CI: 91.7-97.8) for late-onset preeclampsia. The Triage assay sensitivity and specificity was: 96.4% (95% CI: 89.8-99.3) and 88.5% (95% CI: 82.8-92.8) (early-onset); and 90.5% (95% CI: 83-96) and 64.5% (95% CI: 57.8-70.9) (late onset). Conclusions: The fully automated Elecsys immunoassay sFlt-1/PlGF ratio provides improved diagnostic utility over the Triage PlGF assay with improved specificity for the clinical management of pregnant women with suspected preeclampsia/HELLP syndrome.
To evaluate the influence of the soluble fms-like tyrosine kinase 1/placental growth factor ratio... more To evaluate the influence of the soluble fms-like tyrosine kinase 1/placental growth factor ratio in physicians' decision making in pregnant women with signs and symptoms of preeclampsia in routine clinical practice. A multicenter, prospective, open, non-interventional study enrolled pregnant women presenting with preeclampsia signs and symptoms in several European perinatal care centers. Before the soluble fms-like tyrosine kinase 1/placental growth factor ratio result was known, physicians documented intended clinical procedures using an iPad® application (data locked/time stamped). After the result was available, clinical decisions were confirmed or revised and documented. An independent adjudication committee evaluated the appropriateness of decisions based on maternal/fetal outcomes. Clinician decision making with regard to hospitalization was the primary outcome. In 16.9% of mothers (20/118) the hospitalization decision was changed after knowledge of the ratio. In 13 women...
Objectives To assess the economic impact of introducing into clinical practice in the UK the solu... more Objectives To assess the economic impact of introducing into clinical practice in the UK the soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test for guiding the management of pre-eclampsia. Methods We used an economic model estimating the incremental value of information, from a UK National Health Service payer's perspective, generated by the sFlt-1/PlGF ratio test, compared with current diagnostic procedures, in guiding the management of women with suspected pre-eclampsia. The economic model estimated costs associated with the diagnosis and management of pre-eclampsia in pregnant women between 24 + 0 and 36 + 6 weeks' gestation, managed in either a 'test' scenario in which the sFlt-1/PlGF test is used in addition to current diagnostic procedures, or a 'no-test' scenario in which clinical decisions are based on current diagnostic procedures alone. Test characteristics and resource use were derived from PROGNOSIS, a non-interventional study in women presenting with clinical suspicion of pre-eclampsia. The main outcome measure from the economic model was the cost per patient per episode of care, from first suspicion of pre-eclampsia to birth. Results Introduction of the sFlt-1/PlGF ratio test into clinical practice is expected to result in cost savings of £344 per patient compared with a no-test scenario. Savings are generated primarily through an improvement in diagnostic accuracy and subsequent reduction in unnecessary hospitalization. Conclusions Introducing the sFlt-1/PlGF ratio test into clinical practice in the UK was shown to be cost-saving by reducing unnecessary hospitalization of women at low risk of developing pre-eclampsia. In addition, the test ensures that those women at higher risk are identified and managed appropriately.
The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception, 2007
To assess clinical experience with NuvaRing in daily practice in Switzerland, including a large s... more To assess clinical experience with NuvaRing in daily practice in Switzerland, including a large subgroup of young women (aged < or = 22 years). Open, prospective, multicentre, observational clinical experience study to investigate cycle control, acceptability and usage of NuvaRing. Altogether, 2642 women participated in the programme and were included in the analysis, of which 658 were aged < or = 22 years (25% of the total group). A total of 744 women (28% of the total group) discontinued NuvaRing use; the main reason was adverse events (11% of all users). In younger women, there was a shift from moderate (-18%) and heavy (-45%) bleeding to mild bleeding (+71%) and dysmenorrhoea decreased by 60%, despite previous hormonal contraception use by 83% of women. Most women found ring insertion and removal to be straightforward (>95%), and were satisfied with its use (85%), primarily for the ring's once-a-month application (81%). Data were very similar for the total group. Cy...
Objective: To evaluate a new fully automated assay measuring antim€ ullerian hormone (AMH; Roche ... more Objective: To evaluate a new fully automated assay measuring antim€ ullerian hormone (AMH; Roche Elecsys) against antral follicle count in women of reproductive age. Design: Prospective cohort study. Setting: Hospital infertility clinics and academic centers. Patient(s): Four hundred fifty-one women aged 18 to 44 years, with regular menstrual cycles. Intervention(s): None. Main Outcome Measure(s): AMH and antral follicle count (AFC) determined at a single visit on day 2-4 of the menstrual cycle. Result(s): There was a statistically significant variance in AFC but not in AMH between centers. Both AFC and AMH varied by age (overall Spearman rho À0.50 for AFC and À0.47 for AMH), but there was also significant between-center variation in the relationship between AFC and age but not for AMH. There was a strong positive correlation between AMH and AFC (overall spearman rho 0.68), which varied from 0.49 to 0.87 between centers. An agreement table using AFC cutoffs of 7 and 15 showed classification agreement in 63.2%, 56.9% and 74.5% of women for low, medium, and high groups, respectively. Conclusion(s): The novel fully automated Elecsys AMH assay shows good correlations with age and AFC in women of reproductive age, providing a reproducible measure of the growing follicle pool. (Fertil Steril Ò 2015;103: 1074-80. Ó2015 by American Society for Reproductive Medicine.
To assess how routine clinical use of the Roche fully automated Elecsys® sFlt-1/PlGF test changes... more To assess how routine clinical use of the Roche fully automated Elecsys® sFlt-1/PlGF test changes decision-making of physicians to hospitalize pregnant women with suspected preeclampsia. The Preeclampsia Open Study (PreOS) study is a multicenter, prospective, open-label, non-interventional study in 150 women showing signs and symptoms of preeclampsia (suspected preeclampsia). Physicians record their intended procedures before and after knowledge of participants' sFlt-1/PlGF ratio. The study is conducted at five investigational sites in Germany and Austria. The PreOS study will provide evidence on how sFlt-1/PlGF ratio testing influences clinical decision-making in women with suspected preeclampsia in real-world clinical practice.
Background: Preeclampsia is defined as new onset of hypertension and proteinuria at gestational w... more Background: Preeclampsia is defined as new onset of hypertension and proteinuria at gestational week 20 or after. However, use of these measures to predict preeclampsia before its clinical onset is unreliable, and evidence suggests that preeclampsia, eclampsia, or hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome may develop without hypertension or proteinuria being evident. Because of its unpredictability, varying clinical presentation and potential adverse outcomes, pregnant women with suspected preeclampsia require intensive monitoring or hospitalization. Beyond preeclampsia diagnosis, there is a high unmet medical need for more reliable predictive markers for preeclampsia to improve maternal and fetal outcomes and reduce unnecessary hospital admissions. An imbalance of circulating angiogenic and antiangiogenic factors, including raised soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased placental growth factor (PlGF), has been found in women diagnosed with preeclampsia and before clinical onset of the disease. The PRediction of short-term Outcome in preGNant wOmen with Suspected preeclampsIa Study (PROGNOSIS) was designed to investigate the use of the sFlt-1/PlGF ratio in the short-term prediction of preeclampsia. Methods/Design: This global, multicenter, prospective, double-blind, non-interventional study aims to derive and validate cutoffs for the sFlt-1/PlGF ratio, to rule out (for 1 week) or rule in (within 4 weeks) the occurrence of preeclampsia/eclampsia/HELLP syndrome. Eligible participants are women presenting at 24 to <37 weeks' gestation with clinical suspicion of, but not manifest preeclampsia/eclampsia/HELLP syndrome. Clinical assessments, maternal serum sFlt-1/PlGF sampling and documentation of maternal/neonatal outcomes are performed at regular intervals, using strict diagnostic criteria for preeclampsia-related conditions and outcomes. Serum sFlt-1 and PlGF analysis will be performed using fully automated Elecsys® immunoassays. Investigators and participants will remain blinded to the results. Target recruitment is 1000 participants. Health economic analysis is also planned. Discussion: The results of PROGNOSIS will provide the most comprehensive evidence to date on the accuracy of the sFlt-1/PlGF ratio for short-term prediction of preeclampsia/eclampsia/HELLP syndrome. Adoption of the sFlt-1/PlGF test in clinical practice has the potential to reduce the frequency of adverse pregnancy outcomes for both mother and fetus, and decrease healthcare costs associated with unnecessary hospitalization of women with suspected preeclampsia.
A method for predicting the risk for a female subject, to develop at least an adverse consequence... more A method for predicting the risk for a female subject, to develop at least an adverse consequence which be related to preeclampsia, after giving birth to a child, which process comprises the steps of: ) measured in a first sample obtained from a female subject with a pregnancy uneventful, before giving birth to the child, (i) the level of the biomarker sFlt-1 (tyrosine kinase fms-like type 1, soluble) or the level of the biomarker Endoglin, and (ii) the level biomarcardor PIGF (placental growth factor), b) calculating the first ratio factor biomarker levels, as measured in step a), c ) measuring in a second sample obtained from said female subject, after giving birth to a child, the biomarker levels measured in step a), d) calculating the second factor ratio of the levels measured in step c), e) comparing the segund or factor in relation to the first factor relationship.
The diagnosis of preeclampsia in China currently relies on limited clinical signs and unspecific ... more The diagnosis of preeclampsia in China currently relies on limited clinical signs and unspecific laboratory findings. These are inadequate predictors of preeclampsia development, limiting early diagnosis and appropriate management. Previously, the Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia Study (PROGNOSIS) and PROGNOSIS Asia demonstrated that a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio of ≤38 can be used to rule out preeclampsia within 1 week, with negative predictive values of 99.3 and 98.6%, respectively. This is an exploratory sub-analysis of the Chinese cohort (n = 225) of the PROGNOSIS Asia study. The primary objectives were to assess the predictive performance of using the sFlt-1/PlGF ratio to rule out preeclampsia within 1 week and to rule in preeclampsia within 4 weeks. The sFlt-1/PlGF ratio was also examined for short-term prediction of fetal adverse outcomes, maternal adverse outcomes, and time to ...
Introduction Clinical signs and symptoms of preeclampsia are known to be poorly predictive of who... more Introduction Clinical signs and symptoms of preeclampsia are known to be poorly predictive of who will develop the condition, prompting the investigation of angiogenic biomarkers as potential diagnostic and predictive aids. The Elecsys® immunoassay soluble fms-like tyrosine kinase (sFlt-1)/placental growth factor (PlGF) ratio is Conformite Europeenne-In Vitro Diagnostics approved as a diagnostic aid for preeclampsia, and as an aid in the short-term prediction of preeclampsia (rule out and rule in) in pregnant women with suspected preeclampsia in conjunction with other diagnostic and clinical information. In the Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia Study (PROGNOSIS), a cut-off value of 38 was derived and validated to rule out preeclampsia and HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome within one week (Zeisler et al. N Engl J Med 2016;374:13–22). However, the ability of the sFlt-1/PlGF ratio to rule out preeclamp...
Objectives Determine variability of serum anti-Müllerian hormone (AMH) levels during ovulatory me... more Objectives Determine variability of serum anti-Müllerian hormone (AMH) levels during ovulatory menstrual cycles between different women (inter-participant), between non-consecutive cycles (inter-cycle) and within a single cycle (intra-cycle) in healthy women. Methods Eligible participants were women aged 18–40 years with regular ovulatory menstrual cycles. Serum samples were collected every second day during two non-consecutive menstrual cycles. AMH levels were measured in triplicate using the Elecsys® AMH Plus immunoassay (Roche Diagnostics). AMH level variability was evaluated using mixed-effects periodic regression models based on Fourier series. The mesor was calculated to evaluate inter-participant and inter-cycle variability. Inter- and intra-cycle variability was evaluated using peak-to-peak amplitudes. Separation of biological and analytical coefficients of variation (CVs) was determined by analysing two remeasured AMH levels (with and without original AMH levels). Results A...
Personalized health care (PHC) or precision medicine is a new medical concept that aids in treatm... more Personalized health care (PHC) or precision medicine is a new medical concept that aids in treatment decisions for patients by tailoring them to their individual needs. It often employs genetic testing to select appropriate and optimal therapies (pharmacogenomics). Although this concept is widely applied in oncology, the field of hypertension is still in the early stages and "personalization" is currently limited to tailoring antihypertensive treatment according to age, comorbidities, and ethnicity. Despite the fact that incomplete/lack of treatment response occurs in 10-30% of hypertensive patients for angiotensin-converting enzyme (ACE) inhibitors and in 15-25% for β-blockers, major continental guidelines still recommend the use of antihypertensive agents in a "onesize-fits-all" approach, neglecting the 1977 postulation of the Joint National Committee that "all patients must receive individualized therapy programs." The arrival of molecular testing offers new possibilities to differentiate monogenetic from polygenetic disorders and to identify associations between hypertension and drug response to corresponding genes. Up to 50% of the variation in blood pressure (BP) is attributable to genetic factors. Polymorphisms have been identified and studied in genes for BPmodifying receptors, such as ADBR (β-adrenergic receptors), and pharmacological pathways (GNB3, RAAS system). Approximately, one-quarter of the currently analyzed gene polymorphisms demonstrate significant pharmacogenetic effects (ADD1 Gly460Trp and the insertion/deletion [I/D] polymorphism in intron 16 of the ACE gene). Several large screening studies are currently ongoing to assess the impact on efficacy of antihypertensive medication of variants in hypertension-susceptibility genes. The GenHAT substudy of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) assessed the predictive validity of the ACE I/D genotype for coronary heart disease. The Family Blood Pressure Program included 11,079 participants to map genetic variants associated with hypertension. In this review chapter, we display the current body of knowledge regarding PHC in the treatment of hypertension. In particular, we highlight genetic variants associated with hyperten
Clinical Chemistry and Laboratory Medicine (CCLM), 2014
Background: This study aims to evaluate the performance of the soluble Fms-like tyrosine kinase-1... more Background: This study aims to evaluate the performance of the soluble Fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio to predict early-onset, preterm and severe preeclampsia at mid-pregnancy in asymptomatic women. Methods: Based on a prospective cohort of 7929 pregnant women from the Quebec City metropolitan area, a nested case-control study was performed including 111 women who developed preeclampsia and 69 women with gestational hypertension matched with 338 normotensive women. Serum sFlt-1 and PlGF were measured between 20 and 32 weeks of gestation. The performance of the sFlt-1/ PlGF ratio, expressed as raw values and multiples of the median (MoM) for the prediction of early-onset, preterm and severe preeclampsia was evaluated. Results: Women who developed preeclampsia had significantly higher MoM sFlt-1/PlGF ratio (p < 0.001). In the early-onset preeclampsia group, the median of the MoM distribution was 24.0 and the area under the receiver operating characteristic curve (AUC) was 0.977, giving sensitivities of 77.8% and 88.9% at false-positive rates of 5% and 10%. Positive predictive values (PPV) were 2.5% and 1.5%, respectively. In a subset between 26 and 32 weeks of gestation, at a threshold of 30, the sFlt-1/PlGF ratio yielded 100% specificity and identified, respectively, 85.7% and 65.2% of women who developed early-onset and preterm preeclampsia. Conclusions: The sFlt-1/PlGF ratio has the potential to predict early-onset and preterm preeclampsia at midpregnancy in asymptomatic women. However, care must be paid to the prevalence of early-onset preeclampsia in the population since low prevalence reduces PPV and may hamper clinical utility.
Details of the assumed interventions according to intensity of patient management. Summary of int... more Details of the assumed interventions according to intensity of patient management. Summary of interventions that may be performed under each management level according to German maternity policy guidelines and the S1-guideline for hypertensive pregnancy illnesses. (DOCX 16 kb)
Comparison of UK and German economic models. Key similarities and differences between the UK [1] ... more Comparison of UK and German economic models. Key similarities and differences between the UK [1] and German economic models used to determine the incremental value of the sFlt-1/PlGF ratio test (cut-off 38) for guiding the management of women with suspected preeclampsia are presented. (DOCX 16 kb)
Objective: The Elecsys ® immunoassay sFlt-1/PlGF ratio and the Triage ® PlGF assay were compared ... more Objective: The Elecsys ® immunoassay sFlt-1/PlGF ratio and the Triage ® PlGF assay were compared (in a prospective, multicenter, case-control study) for diagnosis of preeclampsia/hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. Methods: Women in European perinatal care centers with singleton pregnancies were enrolled: 178 cases had confirmed preeclampsia and 391 controls had normal outcome. Patients in the preeclampsia/HELLP syndrome group were matched pairwise by gestational week to healthy controls (1:2). Maternal blood samples were analyzed using (a) fully automated Elecsys PlGF and Elecsys sFlt-1 immunoassays with two cutoffs (early-onset [<34 weeks] ≤33, ≥85; late-onset [≥34 weeks] ≤33, ≥110), and (b) Triage PlGF immunoassay (single cutoff). Diagnostic performance and utility were assessed. Results: Respectively, 83 and 95 women had early-onset or late-onset preeclampsia/HELLP syndrome. The overall diagnostic performance of the Elecsys immunoassay sFlt-1/PlGF ratio (area under the curve [AUC] 0.941) was higher than for Triage PlGF (AUC 0.917). The Elecsys immunoassay sFlt-1/PlGF ratio sensitivity and specificity was: 94.0% (95% confidence interval [CI] 86.5-98.0) and 99.4% (95% CI: 96.8-99.9) for early-onset preeclampsia; and 89.5% (95% CI: 81.5-94.8) and 95.4% (95% CI: 91.7-97.8) for late-onset preeclampsia. The Triage assay sensitivity and specificity was: 96.4% (95% CI: 89.8-99.3) and 88.5% (95% CI: 82.8-92.8) (early-onset); and 90.5% (95% CI: 83-96) and 64.5% (95% CI: 57.8-70.9) (late onset). Conclusions: The fully automated Elecsys immunoassay sFlt-1/PlGF ratio provides improved diagnostic utility over the Triage PlGF assay with improved specificity for the clinical management of pregnant women with suspected preeclampsia/HELLP syndrome.
To evaluate the influence of the soluble fms-like tyrosine kinase 1/placental growth factor ratio... more To evaluate the influence of the soluble fms-like tyrosine kinase 1/placental growth factor ratio in physicians' decision making in pregnant women with signs and symptoms of preeclampsia in routine clinical practice. A multicenter, prospective, open, non-interventional study enrolled pregnant women presenting with preeclampsia signs and symptoms in several European perinatal care centers. Before the soluble fms-like tyrosine kinase 1/placental growth factor ratio result was known, physicians documented intended clinical procedures using an iPad® application (data locked/time stamped). After the result was available, clinical decisions were confirmed or revised and documented. An independent adjudication committee evaluated the appropriateness of decisions based on maternal/fetal outcomes. Clinician decision making with regard to hospitalization was the primary outcome. In 16.9% of mothers (20/118) the hospitalization decision was changed after knowledge of the ratio. In 13 women...
Objectives To assess the economic impact of introducing into clinical practice in the UK the solu... more Objectives To assess the economic impact of introducing into clinical practice in the UK the soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test for guiding the management of pre-eclampsia. Methods We used an economic model estimating the incremental value of information, from a UK National Health Service payer's perspective, generated by the sFlt-1/PlGF ratio test, compared with current diagnostic procedures, in guiding the management of women with suspected pre-eclampsia. The economic model estimated costs associated with the diagnosis and management of pre-eclampsia in pregnant women between 24 + 0 and 36 + 6 weeks' gestation, managed in either a 'test' scenario in which the sFlt-1/PlGF test is used in addition to current diagnostic procedures, or a 'no-test' scenario in which clinical decisions are based on current diagnostic procedures alone. Test characteristics and resource use were derived from PROGNOSIS, a non-interventional study in women presenting with clinical suspicion of pre-eclampsia. The main outcome measure from the economic model was the cost per patient per episode of care, from first suspicion of pre-eclampsia to birth. Results Introduction of the sFlt-1/PlGF ratio test into clinical practice is expected to result in cost savings of £344 per patient compared with a no-test scenario. Savings are generated primarily through an improvement in diagnostic accuracy and subsequent reduction in unnecessary hospitalization. Conclusions Introducing the sFlt-1/PlGF ratio test into clinical practice in the UK was shown to be cost-saving by reducing unnecessary hospitalization of women at low risk of developing pre-eclampsia. In addition, the test ensures that those women at higher risk are identified and managed appropriately.
The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception, 2007
To assess clinical experience with NuvaRing in daily practice in Switzerland, including a large s... more To assess clinical experience with NuvaRing in daily practice in Switzerland, including a large subgroup of young women (aged < or = 22 years). Open, prospective, multicentre, observational clinical experience study to investigate cycle control, acceptability and usage of NuvaRing. Altogether, 2642 women participated in the programme and were included in the analysis, of which 658 were aged < or = 22 years (25% of the total group). A total of 744 women (28% of the total group) discontinued NuvaRing use; the main reason was adverse events (11% of all users). In younger women, there was a shift from moderate (-18%) and heavy (-45%) bleeding to mild bleeding (+71%) and dysmenorrhoea decreased by 60%, despite previous hormonal contraception use by 83% of women. Most women found ring insertion and removal to be straightforward (>95%), and were satisfied with its use (85%), primarily for the ring's once-a-month application (81%). Data were very similar for the total group. Cy...
Objective: To evaluate a new fully automated assay measuring antim€ ullerian hormone (AMH; Roche ... more Objective: To evaluate a new fully automated assay measuring antim€ ullerian hormone (AMH; Roche Elecsys) against antral follicle count in women of reproductive age. Design: Prospective cohort study. Setting: Hospital infertility clinics and academic centers. Patient(s): Four hundred fifty-one women aged 18 to 44 years, with regular menstrual cycles. Intervention(s): None. Main Outcome Measure(s): AMH and antral follicle count (AFC) determined at a single visit on day 2-4 of the menstrual cycle. Result(s): There was a statistically significant variance in AFC but not in AMH between centers. Both AFC and AMH varied by age (overall Spearman rho À0.50 for AFC and À0.47 for AMH), but there was also significant between-center variation in the relationship between AFC and age but not for AMH. There was a strong positive correlation between AMH and AFC (overall spearman rho 0.68), which varied from 0.49 to 0.87 between centers. An agreement table using AFC cutoffs of 7 and 15 showed classification agreement in 63.2%, 56.9% and 74.5% of women for low, medium, and high groups, respectively. Conclusion(s): The novel fully automated Elecsys AMH assay shows good correlations with age and AFC in women of reproductive age, providing a reproducible measure of the growing follicle pool. (Fertil Steril Ò 2015;103: 1074-80. Ó2015 by American Society for Reproductive Medicine.
To assess how routine clinical use of the Roche fully automated Elecsys® sFlt-1/PlGF test changes... more To assess how routine clinical use of the Roche fully automated Elecsys® sFlt-1/PlGF test changes decision-making of physicians to hospitalize pregnant women with suspected preeclampsia. The Preeclampsia Open Study (PreOS) study is a multicenter, prospective, open-label, non-interventional study in 150 women showing signs and symptoms of preeclampsia (suspected preeclampsia). Physicians record their intended procedures before and after knowledge of participants' sFlt-1/PlGF ratio. The study is conducted at five investigational sites in Germany and Austria. The PreOS study will provide evidence on how sFlt-1/PlGF ratio testing influences clinical decision-making in women with suspected preeclampsia in real-world clinical practice.
Background: Preeclampsia is defined as new onset of hypertension and proteinuria at gestational w... more Background: Preeclampsia is defined as new onset of hypertension and proteinuria at gestational week 20 or after. However, use of these measures to predict preeclampsia before its clinical onset is unreliable, and evidence suggests that preeclampsia, eclampsia, or hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome may develop without hypertension or proteinuria being evident. Because of its unpredictability, varying clinical presentation and potential adverse outcomes, pregnant women with suspected preeclampsia require intensive monitoring or hospitalization. Beyond preeclampsia diagnosis, there is a high unmet medical need for more reliable predictive markers for preeclampsia to improve maternal and fetal outcomes and reduce unnecessary hospital admissions. An imbalance of circulating angiogenic and antiangiogenic factors, including raised soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased placental growth factor (PlGF), has been found in women diagnosed with preeclampsia and before clinical onset of the disease. The PRediction of short-term Outcome in preGNant wOmen with Suspected preeclampsIa Study (PROGNOSIS) was designed to investigate the use of the sFlt-1/PlGF ratio in the short-term prediction of preeclampsia. Methods/Design: This global, multicenter, prospective, double-blind, non-interventional study aims to derive and validate cutoffs for the sFlt-1/PlGF ratio, to rule out (for 1 week) or rule in (within 4 weeks) the occurrence of preeclampsia/eclampsia/HELLP syndrome. Eligible participants are women presenting at 24 to <37 weeks' gestation with clinical suspicion of, but not manifest preeclampsia/eclampsia/HELLP syndrome. Clinical assessments, maternal serum sFlt-1/PlGF sampling and documentation of maternal/neonatal outcomes are performed at regular intervals, using strict diagnostic criteria for preeclampsia-related conditions and outcomes. Serum sFlt-1 and PlGF analysis will be performed using fully automated Elecsys® immunoassays. Investigators and participants will remain blinded to the results. Target recruitment is 1000 participants. Health economic analysis is also planned. Discussion: The results of PROGNOSIS will provide the most comprehensive evidence to date on the accuracy of the sFlt-1/PlGF ratio for short-term prediction of preeclampsia/eclampsia/HELLP syndrome. Adoption of the sFlt-1/PlGF test in clinical practice has the potential to reduce the frequency of adverse pregnancy outcomes for both mother and fetus, and decrease healthcare costs associated with unnecessary hospitalization of women with suspected preeclampsia.
A method for predicting the risk for a female subject, to develop at least an adverse consequence... more A method for predicting the risk for a female subject, to develop at least an adverse consequence which be related to preeclampsia, after giving birth to a child, which process comprises the steps of: ) measured in a first sample obtained from a female subject with a pregnancy uneventful, before giving birth to the child, (i) the level of the biomarker sFlt-1 (tyrosine kinase fms-like type 1, soluble) or the level of the biomarker Endoglin, and (ii) the level biomarcardor PIGF (placental growth factor), b) calculating the first ratio factor biomarker levels, as measured in step a), c ) measuring in a second sample obtained from said female subject, after giving birth to a child, the biomarker levels measured in step a), d) calculating the second factor ratio of the levels measured in step c), e) comparing the segund or factor in relation to the first factor relationship.
The diagnosis of preeclampsia in China currently relies on limited clinical signs and unspecific ... more The diagnosis of preeclampsia in China currently relies on limited clinical signs and unspecific laboratory findings. These are inadequate predictors of preeclampsia development, limiting early diagnosis and appropriate management. Previously, the Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia Study (PROGNOSIS) and PROGNOSIS Asia demonstrated that a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio of ≤38 can be used to rule out preeclampsia within 1 week, with negative predictive values of 99.3 and 98.6%, respectively. This is an exploratory sub-analysis of the Chinese cohort (n = 225) of the PROGNOSIS Asia study. The primary objectives were to assess the predictive performance of using the sFlt-1/PlGF ratio to rule out preeclampsia within 1 week and to rule in preeclampsia within 4 weeks. The sFlt-1/PlGF ratio was also examined for short-term prediction of fetal adverse outcomes, maternal adverse outcomes, and time to ...
Introduction Clinical signs and symptoms of preeclampsia are known to be poorly predictive of who... more Introduction Clinical signs and symptoms of preeclampsia are known to be poorly predictive of who will develop the condition, prompting the investigation of angiogenic biomarkers as potential diagnostic and predictive aids. The Elecsys® immunoassay soluble fms-like tyrosine kinase (sFlt-1)/placental growth factor (PlGF) ratio is Conformite Europeenne-In Vitro Diagnostics approved as a diagnostic aid for preeclampsia, and as an aid in the short-term prediction of preeclampsia (rule out and rule in) in pregnant women with suspected preeclampsia in conjunction with other diagnostic and clinical information. In the Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia Study (PROGNOSIS), a cut-off value of 38 was derived and validated to rule out preeclampsia and HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome within one week (Zeisler et al. N Engl J Med 2016;374:13–22). However, the ability of the sFlt-1/PlGF ratio to rule out preeclamp...
Objectives Determine variability of serum anti-Müllerian hormone (AMH) levels during ovulatory me... more Objectives Determine variability of serum anti-Müllerian hormone (AMH) levels during ovulatory menstrual cycles between different women (inter-participant), between non-consecutive cycles (inter-cycle) and within a single cycle (intra-cycle) in healthy women. Methods Eligible participants were women aged 18–40 years with regular ovulatory menstrual cycles. Serum samples were collected every second day during two non-consecutive menstrual cycles. AMH levels were measured in triplicate using the Elecsys® AMH Plus immunoassay (Roche Diagnostics). AMH level variability was evaluated using mixed-effects periodic regression models based on Fourier series. The mesor was calculated to evaluate inter-participant and inter-cycle variability. Inter- and intra-cycle variability was evaluated using peak-to-peak amplitudes. Separation of biological and analytical coefficients of variation (CVs) was determined by analysing two remeasured AMH levels (with and without original AMH levels). Results A...
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